PMID- 2573972 TI - [Monoclonal antibodies specific for K88ab, K88ac and K88ad antigens of Escherichia coli]. AB - A panel of twelve hybridoma cell lines, secreting specific antibodies to K88 adhesin antigens of enterotoxigenic Escherichia coli (ETEC) were established from eight separate fusions between mouse myeloma cell line Sp 2/0-Ag-14 and spleen cells from mice immunized with purified K88 antigens. Among the 12 monoclonal antibodies (MCA), K-A, K-35, K-11, and K-15 were K88a specific and reacted with all K88 adhesin bearing Escherichia coli strains tested, whatever K88ab, K88ac or K88ad they might be, as shown either in enzyme-linked immunosorbent assay (ELISA) or in direct agglutination test, whereas K32, K-4, and K-3 were specific for G88ab, K88ac, and K88ad respectively. The antigen patterns of 33 K88 bearing Escherichia coli strains covering 3 serotypes of K88ab, K88ac, and K88ad were analyzed by the use of these MCAs. The preliminary results showed that all Escherichia strains with the same serotype of K88 antigen shared at least one common type-specific antigenic determinant, that K88ad and K88ac strains enjoyed one common antigenic determinant that did not exist on K88ab strains, and that there were a few K88 antigenic determinants that appeared only on limited Escherichia coli strains of the same K88 serotype. PMID- 2573971 TI - [Features of a natural focus of hemorrhagic fever with a kidney syndrome in various regions of the Crimea]. PMID- 2573973 TI - More on foot punctures. PMID- 2573974 TI - [Testicular retention in children]. PMID- 2573975 TI - [Obstructive bronchitis]. PMID- 2573976 TI - Regulation of acetyl CoA carboxylase mRNA in rat liver by high carbohydrate diet and insulin. AB - Acetyl CoA carboxylase contents in liver cytosol of rats refed a high carbohydrate diet or injected with insulin were measured by an immunoassay method in order to evaluate the effects of dietary carbohydrate and insulin treatment on the control in the amount of acetyl CoA carboxylase. Acetyl CoA carboxylase was purified 1,552 folds with a specific activity of 3.88 units/mg protein from livers of rats refed a high carbohydrate diet for 3 days following a 3-day fasting and the antibody was generated against the purified acetyl CoA carboxylase in a rabbit. Treatment of insulin (1.5 units/100g BW) and a high carbohydrate diet increased the amount of acetyl CoA carboxylase in liver cytosol by 3 times and 10 times, respectively, when compared to the enzyme content found in the control. The synthetic ratio of acetyl CoA carboxylase to total cytosolic proteins was 4 times higher in the insulin-treated group and 10 times higher in the high carbohydrated diet-treated group than the control group. The polysomal RNA contents in liver cytosols were 279% of the control in the insulin-treated group and 365% of the control in the high carbohydrate diet group. Also, the nascent chain of acetyl CoA carboxylase in polysome were 158% of the control in the insulin-treated group and 311% of the control in the high carbohydrate treated group. From these results, it is assumed that the increase of acetyl CoA carboxylase content in the rat liver cells by insulin treatment, or high carbohydrate diet refeeding has resulted from the increased polysomal acetyl CoA carboxylase mRNA, which is directly related to the biosynthesis of this enzyme. PMID- 2573977 TI - [Self-medication--a form of non-compliance]. PMID- 2573978 TI - [Ambulatory therapy regimen in patients following myocardial infarct in relation to echocardiography and the stress test]. AB - In 105 patients at the age of 32-80 years after myocardial infarction the therapy with glycoside, diuretics and coronary pharmaca was analysed in dependence upon anamnesis, clinical treatment, ergometric and echocardiographic findings in the period from the discharge from the hospital to the first year. While glycosides, diuretics and nitrates were frequently prescribed unchanged, the intake of the beta-blockers increased from 19 to 28 per cent and that of the calcium antagonists from 21 to 39 per cent for the first year. In glycosides and diuretics the possible disadvantages of a withdrawal trial in clinically and paraclinically compensated patients were more taken into consideration than the side effects by uncritical administration. On the other hand, the advantages of the beta-receptor blockers and calcium antagonists were obviously not yet exhaustively used. PMID- 2573979 TI - Effect of gastrin-releasing peptide (GRP1-27), neuromedin-C (GRP18-27), and neuromedin-B on gastrin and somatostatin secretion from the rat stomach. AB - In the present study the effects of gastrin-releasing peptide (GRP1-27), its C terminal decapeptide neuromedin-C (GRP18-27) and the related peptide neuromedin-B were examined on the secretion of gastrin and somatostatin-like immunoreactivity (SLI) from the isolated perfused rat stomach at intraluminal pH 7 or pH 2. GRP1 27 and GRP18-27 stimulated gastrin secretion equally effective at concentrations of 10(-10), 10(-9), 10(-8), 10(-7) and 10(6)M at luminal pH 7. In addition neuromedin-B was tested at 10(-11), 10(-10), 10(-8) and 10(-6)M and it increased gastrin release similar to equimolar doses of GRP18-27. At luminal pH 2 GRP1-27 stimulated gastrin secretion at 10(-9), 10(-8), 10(-7) and 10(-6)M while GRP18-27 was only effective at 10(-8) and 10(-7)M. Neuromedin-B elicited a gastrin increase at 10(-8)M similar to GRP18-27 and also at 10(-6)M. All three peptides had no significant effect on SLI release at luminal pH 7. At luminal pH 2 GRP1-27 at 10(-9)M and 10(-6)M and GRP18-27 and neuromedin-B at 10(-10)M elicited a significant stimulation of SLI secretion. These data demonstrate that all three bombesin-like peptides GRP1-27, GRP18-27 and neuromedin-B can stimulate gastrin release at either a neutral or an acidic luminal pH, while SLI release is affected only at an acidic intragastric milieu. This suggests that all three forms of bombesin-like peptides are good candidates for the peptidergic regulation of gastrin release in the rat stomach, while their role in somatostatin release seems to be more restricted. PMID- 2573980 TI - Cellular mechanisms of nitrate action. AB - It is now generally accepted that organic nitrates generate their vasodilator action via production of nitric oxide. However, the cellular location of the metabolic enzyme(s) responsible for such conversion has not been defined. We examined the production of nitric oxide, via chemiluminescence detection, by various cellular fractions of the bovine coronary artery. We were able to show that the highest activity resides in the plasma membrane. Future isolation and characterization of such metabolic systems will greatly assist our understanding of nitrate action and tolerance. Several cellular mechanisms for nitrate tolerance have been proposed. Among the most popular theories is the "intracellular sulfhydryl depletion hypothesis" originally proposed by Needleman et al. The primary supportive data for this mechanism are that exogeneously added thiols (such as N-acetylcysteine) can potentiate the in vivo activity of nitroglycerin and can partially reverse nitrate tolerance. We showed that a cellular-impermeant thiol, viz: glutathione, can also potentiate the hemodynamic effect of nitroglycerin in rats. We subsequently showed that exogenously administered thiols can promote the formation of vasoactive S-nitrosothiols in blood. Thus, the beneficial effects of thiols on nitrate action might be mediated through an extracellular pathway. Another cellular mechanism for nitrate tolerance suggested that tolerance is caused by an alteration of the enzyme, guanylate cyclase. We showed, however, that blood vessels made tolerant to nitroglycerin remain fully responsive (in terms of in vitro relaxation) toward nitric oxide and S-nitrosothiols. These data showed that, as far as relaxation is concerned, nitrate tolerance did not cause a significant alteration of guanylate cyclase activity toward nitric oxide and S-nitrosothiols. PMID- 2573981 TI - [Combination of anti-angina drugs]. AB - Within the last decade it became obvious that the treatment of angina pectoris alone is not sufficient. Modern goals include the optimization of anti-ischemic treatment ("silent myocardial ischemia") without compromising quality of life, as well as the reduction of fatal and non-fatal cardiac events. The failure of nitrates to continuously protect from myocardial ischemia ("nitrate tolerance") requires a modification of the current step-care recommendations for medical treatment. Numerous combinations of nitrates, betablockers and calcium channel blockers compensate for each other regarding their effects on heart rate, contractility, peripheral resistance and coronary blood flow. Recommendations for combination therapy decisively depend on the choice of the first-line drug. Only nitrates reduce myocardial preload by venodilation and substitute for EDRF deficiency. After headaches disappear, nitrates do not affect quality of life and they are cheap. The nitrate-induced acceleration of heart rate should be compensated by the addition of beta-blockers or heart rate-decreasing calcium channel blockers. Therefore, the combination of nitrates with heart-rate increasing calcium channel blockers, such as nifedipine, should be avoided. Many studies have proven the superiority of different double and triple therapies, as compared to their single components. A few reports, however, did not confirm this increase of anti-ischemic efficacy with combination therapy. The improvement of prognosis is proven for beta blockers without ISA in subgroups of patients with acute or post myocardial infarction and can be assumed for nitrates as well. With regard to prognosis, calcium channel blockers were inferior to nitrates and beta blockers. The combination of nitrates with a non-ISA betablocker should be preferred in post myocardial infarction patients with ventricular arrhythmias, whereas the combination of nitrates with a heart rate decreasing calcium channel blocker should be preferred in patients with COPD, severe peripheral arterial disease or severe diabetes. The combination of nitrates with a heart-rate increasing calcium channel blocker should be considered in patients with sinus bradycardia, first degree AV-block, or proven coronary spasm. In patients with congestive heart failure, betablockers and calcium channel blockers should be avoided. To optimize medical treatment of ischemic heart disease, intermittent high dosage ISDN plus a beta blocker without ISA or ISDN plus a calcium channel blocker like verapamil are recommended. Frequently, however, the patient decides by himself, based on unacceptable side effects. PMID- 2573982 TI - Clinical tolerance to nitroglycerin is due to impaired biotransformation of nitroglycerin and biological counterregulation, not to desensitization of guanylate cyclase. AB - We studied the effect of nitroglycerin (NTG), endothelium-derived relaxing factor (EDRF), sydnonimine SIN-1, and sodium nitroprusside (SNP) on vascular tone, cyclic GMP content and activity of soluble guanylate cyclase (GC) (in homogenates) of tolerant (1 h 0.55 mM NTG) and non-tolerant (1 h vehicle) de endothelialized rabbit aortae (RA) as well as on cyclic GMP content of cultured smooth muscle cells (SMC) from RA. Nitrate tolerance significantly attenuated NTG induced vasodilation of precontracted (1.0 microM norepinephrine) RA, increase in cyclic GMP in RA and SMC, and activation of guanylate cyclase in homogenates as compared to controls. In contrast, vasodilation and cyclic GMP increases to NNP, SIN-1, and EDRF (from cultured bovine aortic endothelial cells) were not affected in RA and SMC, despite desensitization of guanylate cyclase to activation with SNP and SIN-1 in homogenized tolerant RA. CONCLUSION: A desensitization of soluble guanylate cyclase to activation with NO can be demonstrated under non physiological conditions (disrupted cells) in homogenates from nitrate tolerant RA. However, in intact cells (in situ or in culture) soluble guanylate cyclase is not desensitized to EDRF, SIN-1 or SNP. Therefore reduced generation of NO from NTG because of impaired biotransformation of NTG must be regarded as the basis of nitrate tolerance. PMID- 2573983 TI - [Mechanism of action of circulating amino acids on the function of the digestive system]. PMID- 2573984 TI - [Ultrasonic monitoring of intravascular transfusion in severe Rhesus incompatibility. Diagnostic and therapeutic aspects after fetal relaxation]. AB - Since October 1985 47 ultrasound-guided intrauterine intravascular transfusions were performed in 14 patients at the Department of Obstetrics and Gynecology of the University of Ulm. All newborns were delivered in good condition. The successful diagnostic and therapeutic management of severe erythroblastosis in a twin pregnancy is described. The twin with severe signs of erythroblastosis had an initial hematocrit of 12% at 26 weeks of gestation. Intravascular transfusion of 60 ml packed red cells raised the hematocrit to 41%. The ascites disappeared completely ten days after the first transfusion. Two further transfusions were performed at 29 and 33 weeks of gestation. The intrauterine intravascular relaxation with Norcuron (Vecuroniumbromid) has proved advantageous in preventing interfering fetal movement. Both newborns were delivered in good condition at 36 weeks of gestation. PMID- 2573985 TI - [The immune structure of the population of the Bashkir ASSR in connection with hemorrhagic fever with renal syndrome and the relation of indices of collective immunity to morbidity and the nature of the landscape]. AB - The study of 9,176 serum samples obtained from all regions and 15 cities of Bashkiria, carried out by the method of radioimmunoassay with the use of the antigen of hemorrhagic fever with the renal syndrome (HFRS), has revealed considerable differences in the size of the natural immune stratum of the population (43.9-0.8%). The size of such immune stratum characterizes the activity of natural foci: the largest immune stratum (25.4%) exists among the population of regions with broad-leaved forests, this stratum is somewhat less (12.2-13.2%) in regions with combined coniferous and broad-leaved forest, in regions with different combinations of broad-leaved forests and steppes, as well as mountain forests. On the Aisko-Kungurskaia forest-steppe territory and in regions characterized by a combination of steppe areas with mountain forests the immune stratum has been found to be even lesser (7.3-8.4%). The least immune stratum (3.4%) exists in steppe regions. By comparing the percentage of the population immune to HFRS and having had the diagnosis of HFRS over the period of 30 years the quality of the clinical diagnosis of this infection on the given territory may be determined. PMID- 2573986 TI - [Use of metoclopramide (cerucal) in Tourette syndrome]. AB - The action of cerucal was investigated in 22 children with Tourette syndrome. Positive effect was obtained in 59.1% of the cases. Personality types were described which presented a continuum between asthenic and psycho-asthenic+ poles. Cerucal proved effective in patients with psycho-asthenic+ traits. PMID- 2573987 TI - [Dopamine deficiency syndrome in children with specific reaction to the treatment with levodopa preparations]. AB - The authors describe the dopamine deficiency syndrome in children with the disease beginning during their first year and peculiar dystonia++ symptoms resulting in a total immobilization and speech loss. All the symptoms of the disease can be removed by low doses of Nakom and reappeared upon the drug withdrawal. Tyrosine hydroxylase studies performed in these patients at various stages of the disease showed an unusual pattern of the enzyme activity differing from that seen in children with similar pathology failing to improve dramatically under the Nakom treatment. PMID- 2573988 TI - Fine needle aspiration cytology of focal nodular hyperplasia of the liver. AB - In five cases, the fine needle aspiration (FNA) cytologic study of ultrasonically detected solitary liver tumors yielded a diagnosis of focal nodular hyperplasia. Cytomorphologically, the lesions were characterized by the presence of both abundant normal hepatocytes and numerous epithelial cells in ductal formations, clusters or tightly packed groups in the FNA samples. In two of the five cases, the cytologic diagnosis was confirmed by subsequent histologic studies; in the remaining three cases, the clinical data were consistent with focal nodular hyperplasia of the liver. All five patients were women, four of whom had used oral contraceptives for long periods of time (5 to 15 years), which has previously been linked to the development of focal nodular hyperplasia of the liver. Based on the findings in this study, FNA cytology should be adequate for making the differential diagnosis of focal nodular hyperplasia versus liver-cell adenoma when solitary liver tumors are detected in such cases; it can yield a morphologic diagnosis and facilitate the decision as to whether surgical intervention is required. PMID- 2573989 TI - The prognostic value of TSH receptor binding and thyroid stimulating antibodies following antithyroid drug treatment of Graves' disease. AB - Following a course of medical therapy for Graves' disease approximately 50% of patients relapse. Previous studies have tried to identify these patients by measuring antibodies to the TSH receptor using a range of assay methods. Such studies have produced widely discrepant results. The aim of the present study was to compare the accuracy with which TSH receptor binding antibodies and thyroid stimulating antibodies could identify cases of relapse and remission. Fifty-six newly diagnosed and previously untreated Graves' disease patients were recruited into the study. At presentation 4 were negative for TSH receptor antibody and 5 negative for TS-ab. The remaining 47 were positive for TSH receptor antibody and TS-ab although correlation of the degree of abnormality between methods was poor (r = 0.13 NS). After 12 months carbimazole treatment 28 patients relapsed during the following year and 19 remained in remission. TSH receptor antibody levels obtained at the end of a 12-month course of treatment correctly identified 93% who relapsed and 95% who remained in remission. TS-ab levels could only correctly identify 68% who relapsed and 53% who remained in remission. These results have shown that the accuracy with which patients likely to relapse can be identified depends on the assay method chosen which may account for some of the discrepancies found in previously published studies. PMID- 2573990 TI - Correlation between the duration of perphenazine catalepsy and pressure maintained tonic immobility under the influence of beta-sympathotropic agents. AB - In rats the effect of i.p. applied beta-adrenomimetic isoprenaline (ISO) 0.4 mg/kg, sulbutamol (SAL) 2mg/kg, beta-adrenoblocker propranolol (PRO) 2 mg/kg and metipranolol (MET) 4 mg/kg on the duration of perphenazine-induced catalepsy (CAT) and pressure-maintained tonic immobility (TI) was studied. It appeared that a mild constant pressure on the rat body permitted to measure the length of duration of TI in adult rats. The time course of changes in the duration of CAT and TI was repeatedly measured in one-hour intervals with different results. While ISO had no effect on the duration of CAT, SAL prolonged it. Both beta symathomimetic compounds prolonged the duration of TI. PRO and MET shortened the duration of CAT. PRO did not influence, MET failed in the first phase but in the second phase it significantly prolonged TI duration. In spite of a certain affinity of both phenomena the two, that is, CAT and TI were not parallely influenced by the betasympathotropic agents used. PMID- 2573991 TI - Neurobiochemical alterations in the brain of aging rats. PMID- 2573992 TI - Prevention of ischemic neuronal damage by alpha 1-adrenoceptor agonist (methoxamine). AB - The effect of methoxamine, an alpha 1-adrenoceptor agonist, on ischemic neuronal damage was studied in the gerbil. The animals were subjected to 5 min of ischemia by bilateral common carotid arteries occlusion. Morphological changes and calcium accumulation were evaluated in the CA1 sector of the hippocampus after 7 days of survival. The degree of ischemic neuronal damage and calcium accumulation in the methoxamine-treated groups were significantly attenuated compared with the saline treated ischemic group. The results suggest that alpha 1-adrenoceptor stimulation prevents ischemic neuronal damage. PMID- 2573993 TI - Plasma levels of gastrin, somatostatin, VIP, insulin and oxytocin during the menstrual cycle in women (with and without oral contraceptives). AB - The aim of the present study was to investigate whether plasma levels of gastrin, somatostatin, insulin, oxytocin, VIP and blood glucose levels vary during the menstrual cycle. Therefore, 19 healthy menstruating women (5 of whom were on low dose oral contraceptives, o.c.) were blood sampled every second to third day during the menstrual cycle. Hormone levels were measured with radio-immunoassay. Gastrin, insulin, VIP and blood sugar levels remained unchanged during the menstrual cycle. Mean somatostatin levels were significantly lower in women receiving o.c. than in women without such medication (p less than 0.05). In women on o.c., somatostatin concentrations were also significantly lower during the menstrual week, than during the rest of the period (p less than 0.01), but in women without o.c., no such change occurred. Mean oxytocin levels were significantly higher in women on o.c. (p less than 0.001) and in these women, oxytocin levels recorded during the menstrual week were significantly lower than during the rest of the period (p less than 0.02). Systolic and diastolic blood pressure values were also significantly higher in women on o.c. (p less than 0.05 and p less than 0.01). In conclusion, these data show that basal plasma concentrations of gastrin, somatostatin, VIP, insulin and glucagon do not vary during the menstrual cycle. However, ingestion of low-dose oral contraceptives causes a significant decrease of somatostatin concentrations and a significant increase in oxytocin levels, suggesting that low doses of estrogens and/or gestagens may influence digestive and metabolic processes. PMID- 2573994 TI - Postpsychotic collapse in schizophrenia. AB - The hospital records of 46 schizophrenic patients were studied retrospectively for postpsychotic collapse (PPC), defined in terms of underactivity. PPC was observed in 38 (83%) patients. The duration of PPC was strongly correlated with the duration of the acute psychotic phase after therapy started, and weakly correlated with the mean dose of antipsychotics per day in the acute psychotic phase, and with age of onset. The authors discuss PPC in terms of the effect of antipsychotics, of psychological reaction, and of understimulation in the hospital setting. PMID- 2573995 TI - Pain relief in terminally ill patients. AB - A systematic approach to identifying the cause of pain and rational use of drug therapy are keys to providing pain relief to cancer patients. Aspirin, acetaminophen and nonsteroidal anti-inflammatory drugs are effective for mild to moderate pain, and they enhance the effectiveness of weak oral narcotics, such as codeine. For severe pain, morphine is the drug of choice. A variety of adjuvant drugs can be used to enhance the effect of narcotics and to treat specific side effects of the disease or of therapy. For the terminally ill patient, a peaceful death with dignity should always be possible. PMID- 2573996 TI - Modulation of human basophil growth in vitro by xiao-qing-long-tang (syo-seiryu to), chai-pu-tang (saiboku-to), qing-fei-tang (seihai-to), baicalein and ketotifen. AB - Our previous study showed the inhibitory effect of Qing-Fei-Tang (Q.F.T.) and baicalein on the leukotriene (LT)B4 synthesis of human alveolar macrophages. It has recently been demonstrated that LTs support various cell growth, and basophil and its precursor numbers increase in atopic patients. Therefore, we examined the effect of anti-allergic drugs, including Q.F.T., Xiao-Qing-Long-Tang (X.Q.L.T.), Chai-Pu-Tang (C.P.T.), baicalein and ketotifen which have been used for treatment of bronchial asthma, on human basophil growth in vitro using cord blood mononuclear cells as a basophil precursor source and conditioned medium of T cell leukemia cell line Mo as a growth factor. Two-week cultured basophil numbers identified by alcian blue-safranin staining and those histamine contents assayed fluorometrically were inhibited by Q.F.T. (1.0 mg/ml), X.Q.L.T. (0.01-1.0 mg/ml), C.P.T. (0.01-1.0 mg/ml), baicalein (1-100 microM) or ketotifen (1-100 microM) in a dose-dependent manner while low dose (0.01-0.1 mg/ml) of Q.F.T. showed an enhancing effect on the basophil growth and the histamine content. However, LTB4 or LTC4 failed in restoring the basophil growth reduced by 1 mg/ml of C.P.T. or 100 microM of ketotifen. These results suggest that anti-allergic drugs may modulate basophil growth and differentiation in vitro and/or in vivo and therefore be useful and reasonable for controlling allergic diseases including bronchial asthma. PMID- 2573997 TI - Topography of the Duchenne muscular dystrophy (DMD) gene: FIGE and cDNA analysis of 194 cases reveals 115 deletions and 13 duplications. AB - We have studied 34 Becker and 160 Duchenne muscular dystrophy (DMD) patients with the dystrophin cDNA, using conventional blots and FIGE analysis. One hundred twenty-eight mutations (65%) were found, 115 deletions and 13 duplications, of which 106 deletions and 11 duplications could be precisely mapped in relation to both the mRNA and the major and minor mutation hot spots. Junction fragments, ideal markers for carrier detection, were found in 23 (17%) of the 128 cases. We identified eight new cDNA RFLPs within the DMD gene. With the use of cDNA probes we have completed the long-range map of the DMD gene, by the identification of a 680-kb SfiI fragment containing the gene's 3' end. The size of the DMD gene is now determined to be about 2.3 million basepairs. The combination of cDNA hybridizations with long-range analysis of deletion and duplication patients yields a global picture of the exon spacing within the dystrophin gene. The gene shows a large variability of intron size, ranging from only a few kilobases to 160-180 kb for the P20 intron. PMID- 2573998 TI - Homologous recombination between the LTRs of a human retrovirus-like element causes a 5-kb deletion in two siblings. AB - The RTVL-H family of human endogenous retrovirus-like elements consists of approximately 1,000 intact members and of a similar number of solitary long terminal repeats (LTRs). In this study, the genetic heterogeneity of these elements has been investigated using unique flanking probes isolated from cDNA clones containing RTVL-H sequences. Four such probes were used to screen a panel of human DNA samples for genetic differences. One of these probes detected a 5.0 kb deletion in two related individuals. Cloning and DNA hybridization analysis indicated that the nondeleted common allele contained an intact RTVL-H element, whereas the deleted variant allele contained only a single LTR. DNA sequence comparisons strongly suggest that the deletion is due to homologous recombination between the 5' and 3' LTRs of the RTVL-H sequence. This is the first reported case of a DNA variation in humans that is due to an LTR-LTR excision event. PMID- 2573999 TI - Chromosome-specific alpha satellite DNA from the centromere of human chromosome 16. AB - To examine the molecular organization of DNA sequences located in the centromeric region of human chromosome 16 we have isolated and characterized a chromosome 16 specific member of the alpha satellite DNA family. The probe obtained is specific for the centromere of chromosome 16 by somatic cell hybrid analysis and by fluorescence in situ hybridization and allows detection of specific hybridizing domains in interphase nuclei. Nucleotide sequence analysis indicates that this class of chromosome 16 alpha satellite (D16Z2) is organized as a series of diverged 340-bp dimers arranged in a tandem array of 1.7-kb higher-order repeat units. As measured by pulsed-field gel electrophoresis, the total D16Z2 array spans approximately 1,400-2,000 kb of centromeric DNA. These sequences are highly polymorphic, both by conventional agarose-gel electrophoresis and by pulsed-field gel electrophoresis. Investigation of this family of alpha satellite should facilitate the further genomic, cytogenetic, and genetic analysis of chromosome 16. PMID- 2574000 TI - Physical linkage of a GABAA receptor subunit gene to the DXS374 locus in human Xq28. AB - We report the physical linkage of the gene encoding one of the subunits of the GABAA receptor (GABRA3) to the polymorphic locus DXS374 on the human X chromosome at Xq28. X-linked manic depression and other psychiatric disorders have been mapped to this region, and thus GABRA3 is a potential candidate gene for these disorders. DXS374--and therefore GABRA3--lies distal to the fragile X locus at a recombination fraction of approximately .15. PMID- 2574001 TI - The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene. AB - The debrisoquine-4-hydroxylase polymorphism is a genetic variation in oxidative drug metabolism characterized by two phenotypes, the extensive metabolizer (EM) and poor metabolizer (PM). Of the Caucasian populations of Europe and North America, 5%-10% are of the PM phenotype and are unable to metabolize debrisoquine and numerous other drugs. The defect is caused by several mutant alleles of the CYP2D6 gene, two of which are detected in about 70% of PMs. We have constructed a genomic library from lymphocyte DNA of an EM positively identified by pedigree analysis to be homozygous for the normal CYP2D6 allele. The normal CYP2D6 gene was isolated; was completely sequenced, including 1,531 and 3,522 bp of 5' and 3' flanking DNA, respectively; and was found to contain nine exons within 4,378 bp. Two other genes, designated CYP2D7 and CYP2D8P, were also cloned and sequenced. CYP2D8P contains several gene-disrupting insertions, deletions, and termination codons within its exons, indicating that this is a pseudogene. CYP2D7, which is just downstream of CYP2D8P, is apparently normal, except for the presence, in the first exon, of an insertion that disrupts the reading frame. A hypothesis is presented that the presence of a pseudogene within the CYP2D subfamily transfers detrimental mutations via gene conversions into the CYP2D6 gene, thus accounting for the high frequency of mutations observed in the CYP2D6 gene in humans. PMID- 2574002 TI - Novel PKU mutation on haplotype 2 in French-Canadians. AB - We analyzed DNA from nine French-Canadian probands from eastern Quebec province; all had hyperphenylalaninemia (phenylketonuria [PKU] or non-PKU forms) caused by mutations at the phenylalanine hydroxylase locus. Analysis of RFLP haplotypes and mutations revealed a novel mutation, an A-to-G transition (met----val) in codon 1 (the translation-initiation codon). It occurred on 5 of the 18 mutant chromosomes and was associated each time with haplotype 2. A proband homozygous for this mutation had the PKU phenotype. In other probands, the codon 1 mutation was inherited once with the splice junction mutation in exon 12 (on haplotype 3), conferring PKU, and was inherited twice with a mutation on haplotype 1, conferring PKU in one proband and non-PKU hyperphenylalaninemia in the other. The other five probands carried mutations, conferring PKU, on the following haplotype combinations: 1/3 (twice), 1/9, 3/4, and 1/1. The mutations on haplotypes 1, 4, and 9 are not yet characterized. This preliminary study reveals a novel PKU mutation and considerable genetic heterogeneity at the phenylalanine hydroxylase locus in French-Canadians. PMID- 2574003 TI - Absence of a single repeat from the coding region of the human involucrin gene leading to RFLP. AB - The human involucrin gene has been mapped to the region q21-q22 of chromosome 1. Three of six Utah families examined were polymorphic for a PstI fragment of the involucrin gene. In one individual, the variant PstI fragment was found by DNA sequencing to be missing one of the 39 repeats that make up two-thirds of the coding region. PMID- 2574004 TI - Population genetics of the highly polymorphic locus D16S7 and its use in paternity evaluation. AB - We have developed a DNA RFLP test to resolve paternity cases in which the accused man is included at a low probability of paternity by conventional testing. The DNA probe p79-2-23 was used to determine the allele frequency distribution for the locus D16S7 in the North American black, Caucasian, and Hispanic racial groups. Approximately 3,500 TaqI-digested DNAs were analyzed from the three populations studied. An apparent continuum of alleles was detected varying in size from 2.9 kb to 8.3 kb. Estimates of the average probability of exclusion were found to be .90 and .79 for the North American black and Caucasian populations, respectively. Gene frequency data for common and rare alleles indicated a potential paternity index ranging from 2 to 450. PMID- 2574005 TI - Ciprofloxacin and the fluoroquinolones. New concepts on the mechanism of action and resistance. AB - Ciprofloxacin, a new fluoroquinolone, is a potent, broad-spectrum antibacterial agent. It rapidly blocks bacterial deoxyribonucleic acid (DNA) replication by inhibiting DNA gyrase, an essential prokaryotic enzyme that catalyzes chromosomal DNA supercoiling. Molecular genetic approaches have been used to study the interaction of 4-quinolones with DNA gyrase from quinolone-sensitive strains and from uropathogenic quinolone-resistant clinical isolates of Escherichia coli. An important mutational locus in the gyrase A gene that confers resistance to ciprofloxacin and other quinolones has been identified, and a new, rapid method to examine clinical isolates for the presence of mutations at this position has been devised. A quinolone resistant gyrA gene has been previously cloned and sequenced from an E. coli clinical isolate. Genetic analysis indicated that resistance resulted from a Ser-83----Trp change in the 875 residue gyrase A protein: two other changes observed in the protein, Asp-678----Glu and Ala-828--- Ser, were neutral. GyrA genes carrying these mutations have now been expressed, corresponding mutant gyrase A proteins purified, and their quinolone resistance properties tested by complementing with gyrase B protein and studying the resulting gyrase activity in an adenosine triphosphate-dependent DNA supercoiling assay. The in vitro DNA supercoiling activity of the A (Ser-83----Trp) mutant subunit complemented with wild-type gyrase B subunit was highly resistant to ciprofloxacin and other 4-quinolones. In contrast, A subunit carrying codon 678 and 828 changes reconstituted a quinolone-sensitive gyrase activity. Thus, quinolone-resistant gyrase A proteins may be readily obtained for study by using high-copy gyrA plasmids. In addition, other quinolone-resistant strains of E. coli have been examined for the presence of mutations at gyrase A codons 82 and 83 using a new analytical method based on a restriction fragment length polymorphism (RFLP). This analysis revealed that seven of eight resistant clinical isolates of E. coli examined carried gyrA mutations at codon 82 or 83, whereas five sensitive strains appeared to possess wild-type sequence. Thus, mutations at codon 83 (and possibly 82) in the gyrA gene frequently confer resistance to 4-quinolones, including ciprofloxacin. The RFLP method described should prove useful in examining strains for such mutations. These results are discussed with regard to the mode of interaction of the 4-quinolones with gyrase. PMID- 2574006 TI - Phase I study of low-dose zidovudine and acyclovir in asymptomatic human immunodeficiency virus seropositive individuals. AB - PURPOSE: The combination of zidovudine and acyclovir has shown in vitro antiretroviral activity and led to short-term improvement in patients with symptomatic human immunodeficiency disease (HIV) disease. We performed a phase I study of zidovudine (500 mg/day) plus acyclovir (2 or 4 g/day) in asymptomatic HIV-seropositive men to investigate pharmacokinetics, safety, tolerance, and immunologic effects of the combination. SUBJECTS AND METHODS: Fifty HIV seropositive homosexual or bisexual men from the San Francisco City Clinic Cohort Study were recruited for the study; of these, 20 met the eligibility criteria. Treatment with zidovudine and acyclovir was open label. Pharmacokinetic, virologic, immunologic, and clinical data were collected periodically over a 24 week period. RESULTS: Pharmacokinetic analysis showed no drug interaction. The combination was generally well tolerated, and hematologic parameters remained stable through 24 weeks. There were no significant changes in total lymphocytes, T4 lymphocytes, overall skin test reactivity, or ability to culture virus from peripheral blood. CONCLUSION: This combination of agents is safe in this population for at least six months. Conclusions about long-term tolerance and efficacy await the results of larger trials with longer follow-up. PMID- 2574007 TI - Usefulness and limitations of regional cardiac sympathectomy by phenol. AB - We evaluated the completeness and extent of regional sympathetic denervation of the left ventricle after epicardial painting with phenol in anesthetized dogs. In a region encircled by phenol, the effect of electrical stimulation of efferent sympathetic fibers on myocardial contractility and coronary vascular resistance was completely abolished within 30 min. Denervation extended to untreated regions innervated by sympathetic fibers crossing the phenol line. For at least 4 h after phenol application, intravenous infusion of isoproterenol or coronary arterial infusion of tyramine increased myocardial contractility in the denervated region; norepinephrine content and neurotransmitter uptake were normal, indicating that nerve terminals, postjunctional receptors, and myocardium remained functional. However, after 3-14 days, tissue catecholamine content and transmitter uptake in the encircled area were markedly reduced. The results suggest that careful evaluation is necessary in selecting a fully innervated control region in studies employing regional sympathetic denervation with phenol. PMID- 2574008 TI - Beta-adrenergic receptors on canine coronary collateral vessels: characterization and function. AB - The present studies were performed to examine the role of beta-adrenergic receptors in modulating smooth muscle tone in mature coronary collaterals. To examine the beta-adrenergic receptor population present, radioligand binding cover slip autoradiographic studies were performed on sections of native canine coronary vessels and sections of coronary collaterals developed after placement of Ameroid constrictors. Specific binding of the nonselective beta-adrenergic antagonist [125I]iodopindolol to vascular smooth muscle in segments of both collaterals and native coronary arteries was saturable and stereospecific. Maximal binding and the potency of beta-adrenergic subtype-selective antagonists were similar in all segments. Beta-adrenergic relaxation of native coronary vessels and collateral vessels were studied in isolated organ chambers after preconstriction with prostaglandin F2 alpha. Both native coronary arteries and collateral segments demonstrated beta-adrenergic-mediated relaxation with affinities for both agonists and antagonists compatible with a mixed population of beta 1- and beta 2-adrenergic receptors. These studies indicate that during development, the new collateral vascular smooth muscle expresses a functional population of beta-adrenergic receptors, comparable to that in native vessels. PMID- 2574009 TI - Influence of lung inflation reflex on vascular capacitance in the systemic circulation. AB - The effects of sustained lung inflation on systemic vascular capacitance (SVC), systemic vascular resistance (SVR), and cardiac sympathetic efferent nerve activity (SENA) were investigated in anesthetized dogs. By use of a total cardiopulmonary bypass, the lungs were inflated to tracheal pressures of 10, 15, and 20 mmHg. Tracheal pressures of 10, 15, and 20 mmHg increased system vascular capacitance by 1.4, 3.1, and 4.3 ml/kg and decreased systemic vascular resistance by 0.11, 0.15, and 0.16 mmHg.kg.min-ml-1, respectively, at low carotid sinus pressure (CSP) of 41 mmHg. SENA showed a concomitant decrease. Bilateral vagotomy attenuated the change in SVR by 69%, SVC by 62%, and SENA by 97% when lungs were inflated to a tracheal pressure of 20 mmHg at a low CSP. These results indicate that lung inflation causes a reflex induced increase in SVC as well as a decrease in both SVR and SENA. The lung inflation reflex is mediated primarily through vagal afferent nerve fibers with a small contribution from other afferent nerve pathways. PMID- 2574010 TI - Species differences in regulation of alpha-adrenergic receptor function. AB - The effects of alpha-adrenergic receptor stimulation with norepinephrine and phenylephrine after beta-adrenergic and muscarinic receptor blockades were compared in conscious baboons, calves, dogs, and rats in which left ventricular (LV) pressure. LV maximum rate of pressure development (dP/dt), and heart rate were measured. Autonomic receptor density was examined in crude sarcolemmal preparations from the hearts. The major physiological differences were observed in rats, where alpha 1-adrenergic receptor stimulation resulted in the greatest (P less than 0.05) increases in LV dP/dt (29 +/- 2%) in response to phenylephrine, 5.0 micrograms/kg, in comparison with responses in dogs (12 +/- 4%), calves (3 +/- 3%), and baboons (1 +/- 2%). This was associated with the greatest (P less than 0.05) alpha 1-adrenergic receptor density in the rat heart (73 +/- 5 fmol/mg) compared with values in the baboon (6 +/- 1 fmol/mg), calf (21 +/- 3 fmol/mg), or dog (10 +/- 3 fmol/mg) myocardium. Thus there are major differences among mammalian species in alpha-adrenergic receptor density and physiological responsiveness to alpha-adrenergic agonists. PMID- 2574012 TI - Clonazepam in treatment of bipolar psychotic patients after discontinuation of neuroleptics. PMID- 2574011 TI - A chart review study of late-onset and early-onset schizophrenia. AB - This chart review study compared 54 schizophrenic patients with onset of illness after age 45 years to 54 young and 22 elderly patients with early-onset schizophrenia (before age 45). The index group was more likely to have visual, tactile, and olfactory hallucinations; a greater number of different types of hallucinations; persecutory delusions; and premorbid schizoid personality traits, and was less likely to have thought disorder and affective flattening, than was either comparison group. Among the two elderly groups, index patients had more auditory and visual sensory impairment. Nearly half (48.1%) of the index patients responded to neuroleptic treatment with complete remission. PMID- 2574013 TI - Premedication with temazepam in minor surgery. The relationship between plasma concentration and clinical effect after a dose of 40 mg. AB - Fourteen patients received oral premedication of temazepam in soft gelatin capsules before minor surgery. The plasma concentrations of temazepam and its sedative, anxiolytic and amnesic effects were measured for 24 hours. Absorption was rapid and peak concentrations occurred 49 minutes after administration. Clinical effects were evident at 30 minutes and persisted for about 4 hours. The decline in plasma concentration was biexponential with a distribution half-life of 1.24 hours. The end of the distribution phase coincided approximately with the termination of its clinical effects. A relationship between plasma concentration and effect was observed; concentrations above 300 ng/ml produced measurable changes in tests of mental function. Patients had recovered fully from the effects of temazepam after 24 hours. This dose of temazepam is reliable and effective as premedication before surgery. PMID- 2574014 TI - 'Cured' myasthenia gravis and neuromuscular blockade. AB - A symptomless myasthenic patient who played representative squash received 0.1 mg/kg of vecuronium and enflurane as part of a general anaesthetic for elective gynaecological surgery. Neuromuscular block was prolonged. The effect of neuromuscular blocking agents and volatile anaesthetics in symptomless myasthenics is discussed. We conclude that these patients should be assumed to be sensitive to such agents. PMID- 2574015 TI - Interaction between nondepolarizing neuromuscular blocking agents and inhalational anesthetics. AB - Although many studies have presented data based on administration of nondepolarizing neuromuscular blocking agents to patients given inhalation anesthesia for 30-45 min, no data exist on the interaction in a clinical situation where the relaxant is administered immediately after the start of anesthesia. We therefore studied the effect of the commonly used inhalation anesthetics, halothane and enflurane, on the clinical pharmacology of atracurium, vecuronium, pipecuronium, and pancuronium. No significant influence of the anesthetic technique on the onset time of the various neuromuscular blocking agents was observed. The duration of action of atracurium, pipecuronium, and pancuronium was significantly prolonged during enflurane anesthesia as compared with the other two anesthetic techniques. The duration of vecuronium blockade was not significantly influenced by enflurane. Halothane, in contrast to enflurane, did not significantly prolong the blockade induced by these agents. The prolongation of atracurium blockade was clinically irrelevant. A fact that is statistically significant but clinically irrelevant is that a cumulative effect with atracurium and vecuronium was only seen during enflurane anesthesia and after the fourth maintenance dose. We conclude that there is no clinical indication that the dosage of atracurium and vecuronium during inhalation anesthesia should be reduced, but the doses of pipecuronium and pancuronium should be reduced when prolonged paralysis is not desired. PMID- 2574016 TI - Recovery from vecuronium neuromuscular blockade following neostigmine administration in infants, children, and adults during halothane anesthesia. AB - To determine whether neostigmine had different effects in pediatric patients during vecuronium neuromuscular blockade, the rate of recovery following neostigmine administration was compared in infants (n = 8), children (n = 10), and adults (n = 10) during nitrous oxide-halothane anesthesia. After induction of anesthesia, patients received 100 micrograms/kg of vecuronium. The EMG response of the adductor pollicis was monitored after train-of-four (TOF) stimulation of the ulnar nerve every 20 s. When the first twitch of TOF spontaneously recovered to 10% of control value, neostigmine was injected (40 micrograms/kg in adults, 30 micrograms/kg in infants and children). During the first few minutes following neostigmine administration, no differences were observed between the three groups. After the 8 min, recovery was more rapid in children than in infants and adults up to and including the 15th min. Ten minutes after neostigmine administration, the first twitch (mean +/- SD) reached 97 +/- 3%, 99 +/- 2%, and 97 +/- 5% of control value in infants, children, and adults, respectively; TOF ratio was greater in children (0.96 +/- 0.03) than in either adults (0.82 +/- 0.17) or in infants (0.83 +/- 0.14) (P less than 0.05). During the first minutes after neostigmine administration, the lack of difference in TOF recovery in the three groups suggests that neostigmine is the main factor of recovery. In contrast, the more complete recovery after the eighth minute in children could be due to the faster rate of spontaneous recovery from vecuronium induced neuromuscular blockade in children. PMID- 2574017 TI - Pharmacokinetic modeling of ethyl loflazepate (Victan) and its main active metabolites. AB - A simultaneous consideration of plasma and urine data of unchanged drug and active metabolites, taking into account the metabolic process of the precursor, is described. The maximum likelihood principle was used to estimate parameters. This methodology is highly efficient in determining the contribution of the two main and active metabolites in the pharmacological response of ethyl loflazepate. It also may serve in the search for optimum dosage regimens in clinical practice. PMID- 2574018 TI - Plantar puncture wounds: controversies and treatment recommendations. AB - Future studies are needed to define the natural history of plantar puncture wounds; delineate optimal initial evaluation techniques; examine the role of broad-spectrum antimicrobials for prophylaxis; treatment, or both; and investigate optimal therapy for immunocompromised patients. PMID- 2574019 TI - [Staphylococcal toxic shock syndrome in pediatrics]. PMID- 2574020 TI - [The management of small stature in children]. PMID- 2574021 TI - [The management of undescended testes in children]. PMID- 2574022 TI - [Double and sequential mammary artery bypass grafts. Apropos of 184 patients]. AB - In this series of 184 patients (pts), 312 internal mammary arteries were used to graft 430 coronary arteries. Two mammary arteries were used in 104 pts and sequential anastomoses were performed in 118 pts. The operative mortality was 1.6% and the peri-operative myocardial infarction was 4.1%. 9% of patients had post-operative complications: 1% of bilateral phrenic paralysis, 2.1% of post operative hemorrhage leading to reoperation, 1.6% of sternal infection, 0.5% of true mediastinal infection, 1.6% of sternal dehiscence and 2.7% of reversible psychiatric illness. A 3 month follow-up was available in 160 pts. 95% of patients became angina free, the thallium scan shown a normal uptake of thallium at maximal stress in the myocardial grafted area in 92% of the patients. PMID- 2574023 TI - ras, c-myc and c-erbB-2 oncoproteins in human breast cancer. AB - The expression of ras, c-myc and c-erbB-2 oncoproteins in 100 human (73 ductal and 27 lobular) breast carcinomas has been examined using an immunohistochemical analysis. The monoclonal antibody Y13 259 has been used for the ras p21, the monoclonal antibody Myc1-9E10 for the c-myc p62 and the polyclonal antibody pAb1 (from Triton Bioscience Inc.) for the c-erbB-2 p185 oncoproteins. The following conclusions can be drawn from the analysis: Of the 100 breast carcinoma cases studied only 14 did not express any of the three oncogenes. The remaining 86 were positive for one or more of the three oncoproteins. Ductal carcinomas expressed oncoproteins in 92% of the cases (67/73), whereas lobular carcinomas expressed them in 70% of the cases (19/27). The most frequently expressed was c-myc p62 in 70% of cases followed by ras p21, 55% and c-erbB-2, 35%. Elevated expression of ras, myc or erbB-2 oncogenes did not correlate with the presence of metastasis in auxiliary lymph nodes, the numbers of infiltrated lymph nodes the grade of the tumor or hormone status. However, there appears to be a correlation between increased ras staining intensity and patient's age, below 50 years. PMID- 2574024 TI - Role of autolysins in the activities of imipenem and CGP 31608, a novel penem, against slowly growing bacteria. AB - The carbapenem imipenem and the penem CGP 31608 demonstrated unusually good bactericidal activity against slowly growing bacteria. In contrast to that of penicillin, the rate of killing was independent of growth rate. In logarithmically growing cells, a decrease in growth rate was paralleled by a decrease in the relative activity of only one of four autolysins measured (membrane-bound endopeptidase), suggesting that autolysis induced by penicillin G may be rate limited by this enzyme. Imipenem, on the other hand, appeared to trigger different autolysins in Escherichia coli, as evidenced by differences in the structure of peptidoglycan after imipenem- versus penicillin-induced autolysis. PMID- 2574025 TI - Nucleotide sequence of the Vibrio alginolyticus glnA region. AB - The nucleotide sequence of a 4 kb fragment containing the Vibrio alginolyticus glnA, ntrB and ntrC genes was determined. The upstream region of the glnA gene contained tandem promoters. The upstream promoter resembled the consensus sequence for Escherichia coli sigma 70 promoters whereas the presumptive downstream promoter showed homology with nitrogen regulated promoters. Four putative NRI binding sites were located between the tandem promoters. The ntrB gene was preceded by a single presumptive NRI binding site. The ntrC gene was located 45 base pairs downstream from the ntrB gene. The V. alginolyticus ntrB and ntrC genes were able to complement ntrB, ntrC deletions in E. coli. PMID- 2574026 TI - [The inhibitory effect of oxatomide, an anti-allergic agent, on eosinophil mediated and eosinophilic cell line-mediated natural cytotoxicity against bronchial epithelial cells]. AB - Recently, eosinophils have been implicated as inflammatory effector cells in allergic and inflammatory reactions such as bronchial asthma. In this study eosinophil-mediated and eosinophilic cell line-mediated natural cytotoxicity against bronchial epithelial cells and the effects of oxatomide, an anti-allergic agent, on their cytotoxicity were investigated. Treatment with oxatomide diminished both eosinophil-mediated and eosinophilic cell line-mediated natural cytotoxicity in vitro. We concluded from these results that oxatomide not only has anti-allergic activity but also anti-inflammatory properties for eosinophils. In addition this method for isolating eosinophils seems to well serve the purpose of evaluating eosinophil function as in this investigation, as we have reported previously. PMID- 2574027 TI - [Arylsulfatase activity of asthmatic children]. AB - Human eosinophil arylsulfatase (AS) is known to inactivate a slow reacting substance of anaphylaxis (SRS-A). Arylsulfatase A (AS-A) and arylsulfatase B (AS B) activity was assayed by a modification of the method of Inoue using chromatography, and peripheral eosinophil cell counts were obtained to observe the circadian rhythm of 6 healthy controls and 7 children with asthma. There was no significant diurnal variation in AS between the two groups. Eosinophil counts of both groups were lower in the morning and higher at night. Theophylline and beta 2 stimulants did not affect these activities significantly. Forty asthmatic children were selected to evaluate AS activity and eosinophil counts during and after attacks. AS-B activity was significantly higher in children during attacks than at other times, 5.70 +/- 2.00 vs. 3.74 +/- 0.66 4 MUnmol/ml/2hr (p less than 0.05). This result was more evident within 24 hours of the attack (p less than 0.01). Eosinophil counts were significantly lower during attack, and there was a negative correlation between the eosinophil counts and AS-B activity. AS-B activity in mild asthmatic children was greater than in severe cases. A significant rise in AS-B was seen in EIB negative asthmatics (p less than 0.01), but no remarkable change was seen in either AS-A or AS-B in the EIB positive group. The data suggest that higher AS-B activity during asthma attacks could inactivate SRS-A and modulate allergic inflammatory reaction. PMID- 2574028 TI - [Effect of azelastine on bronchial hyperresponsiveness]. AB - We have investigated the effect of azelastine on bronchial responsiveness in 25 asthmatics, using methacholine inhalation challenge, (Astograph). Three parameters, initial respiratory resistance (RrsC), bronchial sensitivity (Dmin), and bronchial reactivity (SGrs/GrsC) were studied. After 8 weeks' treatment with 2 mg azelastine b.i.d., Dmin was increased significantly and after 4 weeks an insignificant increase was observed. RrsC and SGrs/GrsC did not change significantly during the 8 week treatment. Recent advances have revealed that various chemical mediators, especially leukotrienes, are closely related to bronchial hyperresponsiveness. Accordingly, the improvement of Dmin observed during azelastine treatment might be ascribed to its inhibitory action on the synthesis and release of leukotrienes. PMID- 2574029 TI - [Influences of anti-allergic drugs on superoxide generation from the hypoxanthine xanthine oxidase system or polymorphonuclear leukocytes]. AB - The influences of anti-allergic drugs on superoxide generation from the hypoxanthine-xanthine oxidase system or polymorphonuclear leukocytes (PMN) were studied by an electron spin resonance assay using 5,5-dimethyl-1-pyrroline-N oxide (DMPO) as a spin trapper. The intensity of DMPO-OOH signal generated from the hypoxanthine-xanthine oxidase system was not influenced by the presence of azelastine, ketotifen, disodium cromoglycate, mequitazine, or methylprednisolone, but it decreased in the presence of AA-673. A kinetic study showed that the second order rate constant for reaction between AA-673 and superoxide anion at pH 7.4 was 2.9 x 10(8)M-1S-1. The relative intensity of DMPO-OOH spin adduct generated from PMN stimulated with phorbol myristate acetate (PMA) or opsonized zymosan (OZ) significantly decreased in the presence of azelastine: from the PMN PMA system, with 10.7 microM concentration of molar concentration causing 50% reduction of the signal intensity (IC50), while from the PMN-OZ system, with 10.5 microM concentration of IC50, and also decreased in the presence of mequitazine: from the PMN-PMA system, with 10.8 microM concentration of IC50, while from the PMN-OZ system, less than 2.0 microM concentration of IC50. These results suggest that some anti-allergic drugs may have anti-inflammatory and anti-oxidative actions due to scavenging superoxide radicals or due to inhibiting superoxide production. PMID- 2574030 TI - [Inhibitory effect of procaterol (beta 2 agonist) on the release of cyclooxygenase products during antigen-induced bronchoconstriction in the guinea pig in vivo]. AB - The purpose of this study was to investigate whether procaterol (beta 2 agonist) inhibits the release of cyclooxygenase products in bronchoalveolar lavage fluid (BALF) during in vivo allergic bronchoconstriction in passively sensitized guinea pigs. Antigen-induced bronchoconstriction was significantly inhibited by pretreatment with procaterol. The concentrations of 6-keto-PGF1 alpha, PGF2 alpha and TXB2 in BALF significantly decreased in guinea pigs pretreated with inhaled procaterol. The concentration of TXB2, which is the stable metabolite of TXA2, a strong bronchoconstrictor, was especially markedly decreased compared with that in the control animals. These data indicate that procaterol (beta 2 agonist) may inhibit the release of chemical mediators during allergic reactions as well as directly decrease the contractility of airway smooth muscle. Consequently, regular inhalation of procaterol may be clinically useful for prophylaxis of bronchial asthma. PMID- 2574031 TI - Cochlear neuroactive substances. AB - We have reviewed the experiments done in our laboratory concerning various cochlear neuroactive substances. Data using chemical neuroanatomy and neurochemical techniques are described. They allow the identification and localization of neuroactive substances which could act as neurotransmitters and/or neuromodulators at the different types of synapses in the organ of Corti. Three hypotheses are presented: (1) the inner hair cells use glutamate as a neurotransmitter, but in addition to its excitatory properties, glutamate may also be involved in pathophysiological events affecting afferent auditory dendrites: (2) subpopulations of both the lateral and medial olivocochlear efferent systems can be differentiated by the neuroactive substances they may use: (3) the base and the apex of the cochlea can be distinguished on the basis of neurochemical data. PMID- 2574032 TI - Identification of LDL receptor gene marker associated with altered levels of LDL cholesterol and apolipoprotein B in baboons. AB - We are studying the genetic factors underlying the common forms of heart disease by identifying genes that affect normal variations in plasma lipid, lipoprotein, and apolipoprotein concentrations in baboons. For these studies we are using cloned human gene probes to identify restriction fragment length polymorphisms (RFLPs) at loci encoding the proteins of cholesterol metabolism. In this report we present the identification and mapping of a polymorphic Ava II cleavage site in intron 17 of the baboon low density lipoprotein (LDL) receptor gene. We determined genotypes for this RFLP on a population of 253 pedigreed baboons and assessed the effect of LDL receptor RFLP genotypes on serum concentrations of LDL cholesterol (LDL-C) and apolipoprotein B (apo B). These measures were obtained for each baboon on each of two diets: a low cholesterol, low fat (basal) diet and a high cholesterol, high saturated fat (atherogenic) diet. Statistical analysis detected a significant association between LDL receptor genotype and serum LDL-C and apo B concentrations on both diets. Homozygotes for the rarer allele had lower serum concentrations of LDL-C and apo B than did homozygotes for the common allele, and with the exception of apo B levels on the basal diet, intermediate levels were observed in heterozygotes. The LDL receptor RFLP accounted for approximately 3% to 7% of the variation in serum LDL-C and apo B concentrations on both diets. PMID- 2574033 TI - Two distinct truncated apolipoprotein B species in a kindred with hypobetalipoproteinemia. AB - Two novel, distinct truncated forms of apolipoprotein B (apo B) designated as apo B-90 and apo B-40 were found in five members of a kindred with hypobetalipoproteinemia. Sodium dodecyl sulfate gels and immunoblots of plasma or low density lipoprotein (LDL) (d = 1.019 to 1.063 g/ml) of the affected members demonstrated the presence of one or both of the truncated apo B bands. Employing four monoclonal anti-LDL antibodies with defined regional specificities, we demonstrated that amino terminal epitopes of the truncated apo Bs were intact, but that 10% and 60%, respectively, of the carboxyl terminal regions were absent. Thrombin digestion of apo B-90 generated an abnormally small T2 fragment, confirming that approximately 550 amino acids had been deleted from the carboxyl terminus of apo B-100. Restriction fragment length polymorphism analysis and variable number of tandem repeat typing of the 3' flanking hypervariable region of the apo B gene made it possible to distinguish all four parental alleles and therefore to follow the inheritance of the apo B variants through the family. This pedigree analysis confirmed the inheritance of the apo B-90 and apo B-40 identified by monoclonal antibody binding studies. Siblings heterozygous for apo B-90 or apo B-40 exhibited greater than 65% lower concentrations of apo B-90 or apo B-40 relative to apo B-100 and had 5th percentile LDL cholesterol concentrations. Compound heterozygotes (apo B-90/apo B-40) had the lowest LDL levels, and their LDL particles were small in size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574034 TI - Regulation of pituitary peptides by the immune system. AB - It has long been thought that the central nervous system is able to influence the progression of disease. Furthermore, there is now overwhelming evidence that the communication pathways are bidirectional. A variety of immune system peptides are now known to be capable of transmitting information from the immune system to the central nervous system. These immunotransmitters include interleukins, interferons and thymosine peptides which have the capability of modulating slow wave sleep as well as the release of neuro- and pituitary peptides. In some instances, release of these peptides during early development may have long lasting, if not permanent effects upon the normal development of neuroendocrine circuits. Collectively these various brain mediated events appear to contribute in various and diverse ways to defense against pathogens. It is becoming more and more apparent that certain abnormalities within the immune system may be the consequence of a neurological abnormality. The converse is also true. PMID- 2574035 TI - Gene polymorphism identified by PvuII in familial lipoprotein lipase deficiency. AB - We previously demonstrated that the PvuII polymorphism is a useful marker to analyze the genetic defects in familial lipoprotein lipase (LPL) deficiency. In this study, we have mapped this polymorphic site and cloned the gene fragments containing this site from a patient and a normal subject. Comparative sequence analysis revealed that a C-T transition occurred in the gene of the patient at the PvuII site in the intron 6. Interestingly, the sequence near the PvuII site showed a significant homology to the consensus sequence of the 3' splice site. In addition, the insertional event into the human LPL gene, which was recently reported for a population of Caucasian patients, was not observed for eight unrelated Japanese patients, suggesting that genetic defects underlying familial LPL deficiency should be heterogeneous among races. PMID- 2574037 TI - Isolation of mutants showing temperature-sensitive cell growth from embryonal carcinoma cells: control of stem cell differentiation by incubation temperatures. AB - Embryonal carcinoma(EC) cells, the undifferentiated stem cells of teratocarcinomas, have many properties in common with pluripotent embryonic cells, and thus provide an excellent system for studying the early events involved in embryonic development and stem cell differentiation. We have isolated three novel mutants with temperature-sensitive(ts) cell growth that were able to differentiate at a non-permissive temperature for cell growth. These mutations affect the progression of the cell cycle, leading to the transient accumulation of cells in a specific phase, the S phase, of the cell cycle, which is likely to be the primary cause of stem cell differentiation of EC cells at non-permissive temperature. Isolation of these mutants strongly supports the notion that there is a close association between the inhibition of DNA synthesis and EC cell differentiation. PMID- 2574036 TI - Sulfhydryl reducing agents promote neutrophil adherence without increasing surface expression of CD11b/CD18 (Mac-1, Mo1). AB - The disulfide reducing agents dithioerythreitol and dithiothreitol, but not oxidized dithiothreitol, induced polymorphonuclear neutrophils to adhere to endothelial cells or to plastic. Adherence was inhibited by monoclonal antibodies 60.1 and 60.3, which are directed to functional epitopes on the CD11b and CD18 polypeptides of the neutrophil membrane adhesion complex (Mac-1, Mo1). The increased adherence induced by the sulfhydryl reducing agents was not accompanied by increased expression of CD11b/CD18. These studies demonstrate that a qualitative alteration in CD11b/CD18 is sufficient to promote neutrophil adherence. PMID- 2574039 TI - Potential histamine H2-receptor antagonists. Synthesis, structure and activity of a few open models related to classical H2-antagonists. AB - A few ethers and oximes structurally related to classical H2-antagonists have been synthetized and tested for their in vitro H2-antagonist activity. The compounds in which cyclic "urea equivalent" groups are joined to a cyclohexylmethyl moiety showed a high increase of activity in comparison with the unsubstituted analogues. This finding supports the hypothesis of the existence of an accessorial binding area on H2-receptor near the site fitted by cyclic "urea equivalent" groups. PMID- 2574038 TI - [Argiopinin-binding proteins from the membrane of the bull cerebral cortex]. AB - The 40 kDa argiopinin-binding glycoprotein has been isolated from the solubilised preparations of bovine cerebrum membranes by means of two-step biospecific chromatography on affinity sorbents with immobilized glutamate and argiopinins. This receptor component displays a specific L-[3H]glutamate binding with Kd = 0.18 +/- +/- 0.019 mumole and Bmax = 43 +/- 4.5 nmole/mg. Amino acid analysis reveals it to be a member of integral membrane proteins. PMID- 2574040 TI - [Pilot study of the action of Doqualast on dietary hyperuricemia in volunteers]. AB - For eight days 8 healthy volunteers were treated with a formula diet and additional 1680 purine base per day. Beginning with day 5, doqualast was administered orally in a dosage of 200 mg t.i.d. Serum uric acid level was lowered by doqualast from 7.84 +/- 0.9 mg/dl to 5.09 +/- 0.8 mg/dl (p less than 0.01). Uric acid clearance increased from 7.6 +/- 2.5 ml/min to 11.5 +/- 2.4 ml/min (p less than 0.05). Excretion of uric acid in urine increased from 622 +/- 231 mg/d to 890 +/- 233 mg/d at the end of therapy. Total cholesterol in serum was lowered from 222 +/- 70 mg/dl to 159 +/- 48 mg/dl (p less than 0.05). The new uric acid lowering drug doqualast was well tolerated clinically. No adverse effects on biochemistry parameters were observed. PMID- 2574041 TI - Characterization of relaxin-stimulated cyclic AMP in cultured rat anterior pituitary cells: influence of dopamine, somatostatin and gender. AB - Relaxin is a hormone associated with pregnancy that relaxes uterine smooth muscle and softens the connective tissues of the cervix and pelvis. In spite of these well-characterized tissue responses, the second messenger system linked to the relaxin receptor and the range of target tissues are only modestly understood. We found that relaxin enhanced the cyclic AMP levels in anterior pituitary cells from adult female rats. Relaxin induced a maximal 5.7 +/- 0.5-fold (mean +/- S.E.M.) stimulation of cyclic AMP accumulation and had an excitatory concentration for half-maximal effect (EC50) of 0.4 +/- 0.1 nM, while human relaxin A and B chains had no such activity (EC50 greater than 1 microM). Pertussis toxin amplified the efficacy of relaxin by 1.5 +/- 0.1-fold, indicating the intervention of a G coupling protein. The response to relaxin was reversible with washing, and desensitized slowly with continuous exposure to relaxin. In an attempt to define the physiological role for relaxin at the anterior pituitary, we found that two of the major hypophysiotrophic hormones of the brain (dopamine and somatostatin) markedly inhibited the relaxin stimulation of cyclic AMP. There was also a significant correlation of the response magnitude with the gender of the donor rat. Anterior pituitary cells from adult males exhibited a mean twofold maximal stimulation after relaxin, compared with the sixfold increase measured in cells from female rats. We hypothesize a novel physiological function of relaxin, that of signalling the feminine anterior pituitary. PMID- 2574042 TI - Effect of protein deficiency on some hypothalamic and pituitary hormones in growing male lambs. An immunohistochemical study. AB - Growing male lambs were fed with diets containing 14.0, 10.8 and 7.6% protein for 3 months to determine their effects on the content of hypothalamic LHRH and SRIH and pituitary LH and GH, using immunohistochemical methods. Lowering the concentration of dietary proteins caused marked changes in the immunoreactivity of these hormones. The immunoreactive (IR) content of LHRH stored in the median eminence was enhanced, and the proportion of LH cells and their IR content increased. Opposite effects were observed in the SRIH/GH system; IR SRIH content stored in the median eminence markedly diminished, and, although hyperplasia of GH cells was observed, their IR content was diminished. This study indicates that prolonged restrictions of protein in the diet of growing male sheep affects the immunoreactive content of the investigated hormones. It seems that they suppress LHRH/LH release and augment GH release, possibly via suppression of hypothalamic somatostatin. PMID- 2574043 TI - The formamidine amitraz as a hyperglycemic alpha-agonist in worker honeybees (Apis mellifera mellifera L.) in vivo. AB - Intra-abdominal injection of amitraz (0.25 nmol per honeybee, i.e., approx 2.3 nmol/g) to emerging worker bees, in vivo, led to a significant hypertrehalosemia (300-400%) followed by a hyperglucosemia (approximately equal to 600%). Maxima were reached at 0.5 and 2 h, respectively. A strong negative correlation between glucosemia and trehalosemia appeared after injection of pure phentolamine (1 nmol per bee), suggesting stimulation of trehalase activities. Simultaneous administration of the alpha-blocker at greater than or equal to 0.25 nmol per individual suppressed the hyperglycemic response of amitraz. The formamidine pesticide thus likely acts on the honeybee alpha-aminergic system. PMID- 2574044 TI - Hemodynamic and endocrinological effects of a new selective alpha 1-blocking agent, terazosin, in patients with essential hypertension. Results of long-term treatment. AB - Thirteen patients with essential hypertension were treated with an alpha 1 adrenoceptor antagonist, terazosin (1 to 4 mg/day) for 12 months. To assess the mechanism of its antihypertensive effect, the hemodynamic and endocrinological responses to terazosin were determined before, 3, and 12 months after the administration of terazosin. Blood pressure significantly decreased within 2 weeks after the start of terazosin and its effect was sustained throughout the 12 month period. Pulse rate did not change except slight increase in the third month. The hemodynamic studies revealed that total peripheral resistance significantly decreased and cardiac output slightly increased, indicating that the antihypertensive effect of terazosin is mainly produced by its vasodilation. Blood volume and plasma volume did not change. Although plasma renin activity remained the same, plasma aldosterone significantly decreased in response to terazosin. Plasma noradrenaline increased in the third month, but returned to the baseline level in the twelfth month. Thus, terazosin monotherapy lowered blood pressure throughout one year without drug tolerance including volume expansion and/or accentuation of renin-angiotensin-aldosterone system or sympathetic function. PMID- 2574045 TI - Hypertension: possible differential risk for blacks in Beta-Blocker Heart Attack Trial (BHAT). AB - Previously reported data document that efficacy of beta-adrenergic antagonists in lowering mortality rates after acute myocardial infarction. Similarly, the higher observed mortality rates among blacks in the Beta-Blocker Heart Attack Trial (BHAT) have been addressed. In this report, we further emphasize the apparent role of prior high blood pressure in the high risk profile of black patients radomized in the BHAT and the similarity in response to therapy to other high risk patients in this study. PMID- 2574046 TI - Novel homeotic genes in Drosophila melanogaster. PMID- 2574047 TI - Vasculitis of the breast. Case report and literature review. AB - A case of isolated vasculitis in the mammary gland of a 68-year-old female is described. Over a few months tender lumps occurred in both breasts. There were no signs of generalized disease. The sedimentation rate was normal and mammographic examination revealed no signs of malignant disease. The tumours were removed and histological examination showed inflammation, thrombosis and necrosis of medium and small arteries. We discuss the possibility of an isolated polyarteritis nodosa localized to the breast. PMID- 2574048 TI - [Biochemicals and their functions in the brain--glucose, and amino acid and amine neurotransmitters]. PMID- 2574049 TI - Effects of xamoterol, a beta 1 adrenoceptor partial agonist, in patients with ischaemic dysfunction of the left ventricle. AB - The effects of xamoterol (200 mg twice a day) in 21 patients with left ventricular dysfunction were studied in a double blind, randomised, crossover, placebo controlled trial with treatment periods of four weeks. Most patients had moderate heart failure (New York Heart Association class II), all had ischaemic heart disease, a history of a myocardial infarction, and symptoms of dyspnoea on exertion. Patients were assessed in terms of exercise duration (bicycle ergometer), clinical signs of heart failure, symptoms and activities, and ejection fraction. Xamoterol increased exercise duration (mean (SD] (from 445 (8) seconds to 484 (8) seconds) and ejection fraction (from 41.9 (1.3)% to 46.6 (1.3)%) and reduced the signs and symptoms of heart failure. The results of this study show that xamoterol is a safe and effective treatment for left ventricular dysfunction resulting from ischaemic heart disease. PMID- 2574050 TI - Inhibition of gastric secretion following single morning or twice daily oral administration of sufotidine to volunteers. AB - 1. The inhibitory effect of sufotidine, a new histamine H2-receptor antagonist, on gastric secretion of acid and pepsin was studied in six healthy male volunteers. This was a three-way, cross-over, randomized, double-blind study. On each of 3 study days, the drug in a dose of 600 mg, or placebo, was administered either once or twice daily at 08.00 and 20.00 h. 2. The morning dose of sufotidine maintained intragastric pH above 3 until 18.00 h. Twice daily sufotidine maintained the pH above 3 throughout the 24 h. The median 24 h concentration of acid was significantly reduced from 86.9 mmol l-1 after placebo to 22.8 mmol l-1 and 4.9 mmol l-1 following the morning only or twice daily dose of sufotidine, respectively. Mean night-time output of acid was reduced by 81% after the morning dose of sufotidine and by 97% following treatment with sufotidine twice daily. 3. We conclude that sufotidine, in the doses studied, markedly inhibits gastric secretion and may therefore prove useful in the treatment of peptic ulceration and oesophagitis. PMID- 2574051 TI - A dose rising study of the safety and effects on serum prolactin of SK&F 101468, a novel dopamine D2-receptor agonist. AB - 1. SK&F 101468, a non phenolic indolone derivative, has been characterised preclinically as a novel, potent and specific dopamine D2-receptor agonist. 2. Its tolerability and effects on serum prolactin were investigated in 14 healthy male volunteers in a study of the first administration of SK&F 101468 to man. 3. Doses between 80 micrograms and 2.5 mg caused statistically significant (P less than 0.05) lowering of basal and food stimulated serum prolactin, relative to placebo, over a 6 h post treatment period. 4. SK&F 101468 was well tolerated up to 1 mg with symptoms of nausea and postural hypotension at higher doses. PMID- 2574053 TI - Differential effect of continuous administration of beta-adrenoceptor antagonists on antipyrine and phenytoin clearance. AB - 1. Antipyrine (1000 mg orally) clearance was studied 3 days before treatment with either atenolol (50 mg twice daily), metoprolol (100 mg twice daily), propranolol (80 mg twice daily) or placebo, and at day 5 and 18 during treatment. Phenytoin (100 mg intravenously) clearance was measured on days 0, 7 and 21 during treatment. 2. Antipyrine clearance was decreased by about 20% after 5 days of treatment with either propranolol or atenolol and this decrease persisted after 18 days of treatment. Antipyrine clearance did not change during treatment with either metoprolol or placebo. Phenytoin clearance did not change during any of the treatments. PMID- 2574052 TI - CNS-related subjective symptoms during treatment with beta 1-adrenoceptor antagonists (atenolol, metoprolol): two double-blind placebo controlled studies. AB - 1. Whilst a number of studies have investigated whether metoprolol and atenolol, the most widely used beta 1-adrenoceptor antagonists, differ with regard to CNS related subjective symptoms, few placebo-controlled studies using standardised questionnaires have been performed. 2. In the present report, the findings of two randomised, double-blind, cross-over studies in healthy volunteers are presented. The subjects were treated with placebo and atenolol (100 mg once daily) (Study 1) and metoprolol (100 mg once daily) and placebo (Study 2). 3. Subjective experiences were evaluated using a standardised instrument, the Minor Symptoms Evaluation-profile (MSE-profile), which was filled in 4, 8 and 24 h after intake of the tablets. A Type A questionnaire was also completed by the subjects. 4. At 4 h both metoprolol and atenolol were found to affect negatively vitality and contentment, but these effects had declined after 8 h. A significant adverse effect on sleep was shown for atenolol compared with placebo, while no negative effect was observed for metoprolol. No significant differences were found in relation to Type A behaviour and beta-adrenoceptor blockade. The number of subjects with Type A personality was, however, low. 5. The results of the studies indicate that the subjective symptoms of the beta 1-adrenoceptor blockers are mild, and that the effects appear consistently with the recognised pharmacokinetic profiles of the two drugs. PMID- 2574054 TI - Acrivastine in two doses compared with placebo in a multicentre, parallel group study for the treatment of seasonal allergic rhinitis. AB - In a placebo controlled, randomised, multicentre study the efficacy and safety of multiple doses of acrivastine, a derivative of the antihistamine tripolidine (Actidil) were evaluated in patients exhibiting symptoms of seasonal allergic rhinitis. Over the 10 day treatment period, 103 patients received, twice daily, either 4 mg and 8 mg of acrivastine or a placebo. Three patients withdrew from the study due to poor symptom control and two due to adverse experiences. The reporting of adverse experiences was evenly distributed between the treatment and placebo periods. Acrivastine did not affect the haematological, biochemical or urinalysis screens. Both 4 mg and 8 mg acrivastine alleviated the symptoms of seasonal allergic rhinitis with significant improvements in the symptom scores for sneezing, running nose and the calculated overall score. In addition, 8 mg acrivastine reduced the symptom scores for watery eyes and itchy throat. Acrivastine was both well tolerated and effective in the treatment of seasonal allergic rhinitis. PMID- 2574055 TI - Catatonia: a new indication for benzodiazepines? PMID- 2574056 TI - Benzodiazepines and catatonia: an overview. PMID- 2574057 TI - High-performance liquid chromatographic determination of beta-adrenoceptor blocking agents in body fluids. AB - Several reports have been published reviewing high-performance liquid chromatographic (HPLC) methods for the determination of beta-adrenoceptor blocking agents (beta-blockers) in biological materials (Flouvat et al., 1981; Mehta, 1983; Marko and Soltes, 1984; Ahnoff et al., 1985; Tkaczykova and Safarik, 1987). Of these, the paper by Mehta (1983) briefly summarizes the interrelationship between physiocochemical properties of beta-blockers with prechromatographic treatment of biological samples, as well as with the HPLC methods used for the determination of 12 beta-adrenoceptor blocking drugs. The work by Ahnoff et al. (1985) concerning the monitoring of cardiovascular drugs also deals with HPLC assays of 18 beta-blockers in plasma. The Appendix to this report presents the great majority of HPLC methods for determining 30 beta blockers in various body fluids. HPLC methods providing resolution and determination of individual beta-blocker enantiomers have not been included since this topic is being covered by Walle and Walle (1989). The Appendix is just a guide to the methods reviewed for the HPLC determination of parent beta-blockers as well as some of their metabolites co-assayed in various body fluids. It does not include details such as the internal standard, recovery, setting of the detector, limit of determination, etc., given in the individual methods listed. The isolation technique of the drug(s) from the given body fluid represents the main step in the sample work-up procedure. Along with this information, only the type of the HPLC column packing and the detection principle used by each method's developers are given. PMID- 2574058 TI - A high performance liquid chromatography/electrochemical assay for glutamatergic neurotransmitters in the rat brain. AB - The release and content of the excitatory amino acid neurotransmitters glutamate and aspartate in rat striatum were determined by liquid chromatography/electrochemistry. This determination was based on precolumn off line derivatization of the amino acids with o-phthaldialdehyde and 2 mercaptoethanol (OPT/2-MCE), and the adducts formed were separated under isocratic conditions and oxidized on a glassy carbon electrode at moderate potential (+0.6 V). The standard and the extracted glutamate when derivatized with OPT/2-MCE produced similar electrochemical and chromatographic characteristics. The detection limit of glutamate was 0.5 pmol. Depolarization induced by the high potassium medium (40 mmol/L) enhanced the release of glutamate and aspartate from superfused rat striatum, whereas the efflux of glutamine remained unchanged. Perfusion (for 60-70 min) removed 50-80% of the free amino acid content of striatal tissue. The method described here is useful in neurochemical investigations of the brain amino acid neurotransmitters. PMID- 2574059 TI - The effect of sulphasalazine on the in vitro activation of human peripheral blood mononuclear cells by phytohemagglutinin P. AB - The in vitro action of sulphasalazine, BW 755-C and indomethacin on phytohemagglutinin P-induced human peripheral blood mononuclear cell activation was studied. Sulphasalazine increased, while indomethacin and BW 755-C decreased, prostaglandin E2 (PGE2) accumulation in activated cultures. When used together with indomethacin or BW 755-C, sulphasalazine did not counteract the inhibition of PGE2 caused by the other two. Sulphasalazine inhibited phytohemagglutinin P induced cell activation in a concentration-dependent manner even when used together with indomethacin or BW 755-C. BW 755-C inhibited cell activation at 350 microM, whereas at 11 microM it only increased sulphasalazine-induced inhibition. The implications of these findings on the etiopathology of inflammatory bowel disease are discussed. PMID- 2574060 TI - Alpha 2-adrenoceptor agonists enhance vasoconstrictor responses to alpha 1 adrenoceptor agonists in the rat tail artery by increasing the influx of Ca2+. AB - 1. The alpha 2-adrenoceptor agonists TL99 (2-(N N-dimethyl)amino-6,7-dihydroxy 1,2,3,4-tetrahydronaphthalene) and UK14304 (5-bromo-6-[2-imidazoline-2-yl-aminol] quinoxaline), in concentrations that are less than 1% of those producing vasoconstriction, enhance vasoconstrictor responses to noradrenaline and phenylephrine in isolated perfused preparations of the rat tail artery. 2. The enhancing effect was abolished when Ca2+ was absent and by the calcium channel blocking drug diltiazem. 3. alpha 2-Adrenoceptor agonists had no effect on the component of the responses to noradrenaline and phenylephrine that is attributable to mobilization of intracellular Ca2+, but enhanced the component attributable to influx of extracellular Ca2+. 4. These results suggest that the enhancing effect of alpha 2-adrenoceptor agonists on responses of the rat tail artery to alpha 1-adrenoceptor agonists involves an increase in Ca2+-influx into smooth muscle cells through Ca2+ channels that are opened when alpha 2 adrenoceptors are activated. PMID- 2574061 TI - Convulsions induced by centrally administered NMDA in mice: effects of NMDA antagonists, benzodiazepines, minor tranquilizers and anticonvulsants. AB - 1. Convulsions were induced reproducibly by intracerebroventricular injection of N-methyl-D-aspartic acid (NMDA) to conscious mice. 2. Competitive (carboxypiperazine-propylphosphonic acid, CPP; 2-amino-7-phosphonoheptanoic acid, AP7) and non-competitive (MK801; phencyclidine, PCP; thienylcyclohexylpiperidine, TCP; dextrorphan; dextromethorphan) NMDA antagonists prevented NMDA-induced convulsions. 3. Benzodiazepine receptor agonists and partial agonists (triazolam, diazepam, clonazepam, Ro 16-6028), classical anticonvulsants (diphenylhydantoin, phenobarbitone, sodium valproate) and meprobamate were also found to prevent NMDA induced convulsions. 4. Flumazenil (a benzodiazepine receptor antagonist) and the GABA agonists THIP and muscimol (up to subtoxic doses) were without effect. 5. Flumazenil reversed the anticonvulsant action of diazepam, but not that of MK801. 6. Results obtained in this model differ somewhat from those described in a seizure model with systemic administration of NMDA. An explanation for this discrepancy is offered. 7. This model is a simple test for assessing the in vivo activity of NMDA antagonists and also expands the battery of chemically-induced seizure models for characterizing anticonvulsants not acting at NMDA receptors. PMID- 2574062 TI - Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones. AB - 1. The effects of benzodiazepines and non-benzodiazepine compounds on the gamma aminobutyric acid (GABA)-induced chloride current (ICl) were studied in frog isolated sensory neurones by use of a concentration-jump (termed 'concentration clamp') technique, under single-electrode voltage-clamp conditions. The drugs used were classified into four categories as follows: full benzodiazepine receptor agonists (diazepam, clonazepam, nitrazepam, midazolam, clotiazepam and etizolam), partial agonists (CL 218,872, Ro 16-6028, Ro 17-1812 and Ro 23-0364), inverse agonists (Ro 15-3505, FG 7142 and beta-CCE) and a benzodiazepine receptor antagonist, Ro 15-1788 (flumazenil). 2. All full agonists at concentrations of 3 x 10(-6) M or less increased dose-dependently the peak amplitude of ICl elicited by 3 x 10(-6) M GABA to twice to three times larger than the control. However, no further augmentation of the GABA response was observed at concentrations of 1 x 10(-5) M or higher. Partial agonists also showed a dose-dependent augmentation of the GABA response at concentrations ranging from 3 x 10(-8) M to 3 x 10(-5) M, but their efficacies of augmentation of the GABA response were only about half or less of those of full agonists. Of the inverse agonists, beta-CCE had a unique dose-dependent effect on the GABA response. Beta-CCE reduced dose-dependently the GABA response at concentrations of less than 3 x 10(-6) M, but augmented it at concentrations of 3 x 10(-5) M and 6 x 10(-5) M. The inverse agonists reduced dose-dependently the GABA response. The benzodiazepine antagonist, flumazenil, slightly augmented the GABA response at concentrations between 3 x 10 7M and 3 x 10 5 M. 3. These results show clear differences in the effects on the GABA response between these four categories of compounds known to affect the benzodiazepine recognition site of the GABA/ benzodiazepine receptor-chloride channel complex. Our experimental system of frog isolated sensory neurones and a 'concentration-clamp' technique appears to be useful for evaluating efficacy of compounds on responses mediated by the GABA/benzodiazepine receptor-chloride channel complex. PMID- 2574063 TI - Inhibition of N-methyl-D-aspartate- and kainic acid-induced neurotransmitter release by omega-conotoxin GVIA. AB - 1. The role of voltage-sensitive calcium channels (VSCC) in N-methyl-D-aspartate (NMDA)- and kainic acid (KA)-evoked neurotransmitter release from rat cortical and hippocampal brain slices was evaluated by determining the effects of omega conotoxin GVIA, an inhibitor of neuronal L- and N-type VSCC, and PN 200-110, a selective inhibitor of L-type VSCC. 2. Selective antagonists of the NMDA receptor ionophore complex, Mg2+, CPP and MK-801, inhibited NMDA- but not KA-evoked release of [3H]-noradrenaline from hippocampal and cortical brain slices. This suggests that cortical and hippocampal receptors are similar and that NMDA and KA act at distinct excitatory amino acid receptor subtypes. 3. [3H]-noradrenaline release induced by both NMDA and KA was similarly inhibited (approximately 30%) by omega-conotoxin GVIA. In contrast, PN 200-110 had no significant effect, although there was a tendency towards inhibition. 4. The results suggest that although NMDA- and KA-receptors are pharmacologically distinct, the N-type, but not the L-type, VSCC plays a small but significant role in neurotransmitter release induced by both NMDA and KA. It remains to be determined whether the N type VSCC are involved in the physiological and/or pathological manifestations of excitatory amino acid receptor stimulation. PMID- 2574064 TI - Effect of palytoxin on the calcium current and the mechanical activity of frog heart muscle. AB - 1. The effect of palytoxin (PTX) on the Ca current (ICa) and the mechanical activity of frog atrial fibres was studied by use of the double sucrose gap voltage clamp technique. 2. In normal Ringer solution, PTX transiently increased the electrically-evoked peak tension which then decreased while a major contracture developed. PTX slowed the time course of the relaxation phase of the evoked tension. 3. Evidence is presented which suggests that the toxin also increased the entry of Ca and Sr via the Na-Ca exchange mechanism. It also induced the development of a Ca-dependent outward current which was inhibited by Sr. 4. In Na-free solution, PTX increased ICa and shifted the reversal potential for Ca towards more negative membrane potentials, thus suggesting that the internal Ca concentration had increased. Current-voltage, tension-voltage, time to peak-voltage and inactivation time constant-membrane potential curves were all shifted towards more negative membrane potentials in the presence of PTX. 5. These effects of PTX are similar to those caused by the increase in internal Ca concentration induced by Na ionophores by way of voltage-dependent Ca influx of the Na-Ca exchange mechanism. PMID- 2574065 TI - 5-Hydroxytryptamine is a possible neurotransmitter of the non-cholinergic excitatory nerves in the longitudinal muscle of rainbow trout stomach (Salmo gairdneri). AB - 1. The neurotransmitter of the non-cholinergic excitatory nerves in the rainbow trout stomach was identified on the basis of the pharmacological properties of the contractile responses to transmural stimulation (TMS) and nicotine. 2. TMS caused tetrodotoxin-sensitive contractions of rainbow trout stomach strips in a frequency-dependent manner (0.5-50 Hz). Atropine (1 microM) significantly decreased the contractile response to low-frequency stimulation (0.5-2 Hz), but did not affect that to high-frequency stimulation (3-20 Hz). 3. The atropine resistant contractile response to TMS (20 Hz) was unaffected by hexamethonium (100 microM), phentolamine (5.4 microM), pyrilamine (1 microM), naloxone (1 microM) or substance P-induced desensitization. 4. 5-Hydroxytryptamine (5-HT, 3 nM-3 microM) caused atropine-resistant contractions in a concentration-dependent manner. In the presence of atropine, methysergide (1 microM) decreased the contractile responses to TMS and 5-HT. 5. Nicotine (3 microM-500 microM) induced atropine-resistant contractions that were completely abolished by tetrodotoxin or hexamethonium. Also methysergide inhibited the contractile responses to nicotine. 6. An acid extract of rainbow trout stomach exhibited atropine-resistant contractions that were decreased by methysergide, in both rainbow trout stomach and guinea-pig ileum longitudinal smooth muscle preparations. 7. The present results indicate that, in longitudinal muscle strips of the rainbow trout stomach, 5-HT is one of the mediators (neurotransmitters) of the non-cholinergic excitatory contractions induced by TMS and nicotine. PMID- 2574067 TI - Sight and insight: brain dopamine receptor occupancy by neuroleptics visualised in living schizophrenic patients by positron emission tomography. PMID- 2574066 TI - Pharmacological characterization of 8-OH-DPAT-induced inhibition of rat hippocampal 5-HT release in vivo as measured by microdialysis. AB - 1. We have previously found that the putative 5-HT1A agonist 8-hydroxy-2-(di-n propylamino) tetralin (8-OH-DPAT) decreases hippocampal 5-hydroxytryptamine (5 HT) release in the anaesthetized rat, as measured by brain microdialysis. The present study attempted to characterize the receptor involved in this response using a range of monoamine receptor antagonists. 2. The classical 5-HT receptor antagonists, metergoline (5 mg kg-1 s.c.), methysergide (10 mg kg-1 s.c.) and methiothepin (10 mg kg-1 s.c.) each reduced dialysate levels of 5-HT which complicated their use as antagonists in these experiments. Nevertheless, pretreatment with metergoline but not methiothepin and methysergide partially reduced the 5-HT response to a maximally effective dose of 8-OH-DPAT (0.25 mg kg 1 s.c.). 3. The mixed 5-HT 1/beta-adrenoceptor antagonist pindolol (8 mg kg-1 s.c.) was without effect on spontaneous 5-HT output but attenuated the effect of both maximally (0.25 mg kg-1 s.c.) and submaximally (0.05 mg kg-1 s.c.) effective dose of 8-OH-DPAT. In comparison, propranolol (10 mg kg-1 s.c.) did not affect 5 HT output when injected alone and did not alter the response to 8-OH-DPAT (0.25 mg kg-1 s.c.). 4. The 5-HT2 receptor antagonist ritanserin (0.2 mg kg-1 s.c.) and the 5-HT3 receptor antagonist BRL 43694 (0.5 mg kg-1 s.c.) neither altered 5-HT output alone nor significantly changed the response to 8-OH-DPAT (0.25 mg kg-1 s.c.). 5. The 8-OH-DPAT (0.25 mg kg-' s.c.) response was not affected by pretreatment with either the dopamine D2-receptor antagonist sulpiride (10mgkg-1 s.c.) or the alpha/alpha 2-adrenoceptor antagonist phentolamine (10mg kg-1 s.c.). 6. We conclude from these data that the decrease of hippocampal 5-HT output induced by 8-OHDPAT does not involve 5-HT2, 5-HT3, adrenoceptors or dopamine D2 receptors and that activation of a 5-HT1 class of receptor seems probable. Full classification of the 8-OH-DPAT response awaits development of a suitably selective 5-HT1 receptor antagonist with low intrinsic activity at the somatodendritic 5-HT autoreceptor. PMID- 2574068 TI - The nature and prevalence of depression in chronic schizophrenic in-patients. AB - Out of 194 chronic schizophrenic in-patients, depressed mood (item 23 of the PSE) was present in 25 (13%). When compared with 25 matched controls, the patients with depressed mood had significantly higher scores on the MADRS and the Beck Depression Inventory. Serious suicidal ideas and auditory hallucinations were significantly more common in the depressed group. However, there were no significant differences between the matched groups in terms of negative symptoms, Parkinsonism, tardive dyskinesia, anticholinergic medication, or current dose of antipsychotic drug, which suggests that the depression identified was not related to drug treatment, nor was it a direct manifestation or misinterpretation of negative symptoms. Over three-month follow-up, the MADRS and Beck scores covaried closely with the presence or absence of depressed mood. This depressive syndrome persisted over the three months in the majority of patients originally depressed. PMID- 2574069 TI - The course of tardive dyskinesia in patients on long-term neuroleptics. AB - Results are presented of five consecutive annual examinations using the Abnormal Involuntary Movement Scale for 101 community-based chronic psychiatric patients. These 101 patients had a history of longer and more consistent neuroleptic treatment than the 231 patients who initially entered the study, so no conclusions about prevalence of TD can be drawn. At each examination two-thirds of this group showed signs of TD; however, only 45% were TD positive at most examinations and 24% were best described as having fluctuating TD status. Of those patients who were consistently TD positive, 82% showed no overall significant change in summed AIMS scores, 11% improved and 7% became worse. PMID- 2574070 TI - Hippocampal neuronal responsiveness to different neurotransmitters in the adult rat after neonatal interference with noradrenaline transmission. AB - In order to test the functional significance of noradrenergic neurotransmission for brain maturation, rat pups were injected daily with clonidine from 8-21 days of postnatal life. In adulthood, single cell responses to microiontophoretically applied neurotransmitters were studied in different layers of the hippocampus. No significant differences were found in neuronal responsiveness to glutamate, GABA, or acetylcholine in the hippocampus of clonidine-treated rats as compared with age-matched controls. However, there was a significantly stronger depression of glutamate-evoked activity of CA1 pyramidal neurons by noradrenaline in the clonidine-treated rats. PMID- 2574071 TI - Dissociating learning and performance: drug and hormone enhancement of memory storage. AB - This paper reviews selected studies examining the enhancing effects of drugs and hormones on learning and memory. Many strategies have been used in an effort to dissociate drug effects on learning from drug effects on other processes affecting the performance of responses. These strategies include the use of tasks with various motivational and response requirements, the use of studies explicitly examining drug influences on performance, the use of posttraining drug administration and the use of various forms of latent learning tasks. It seems clear from these studies that the dissociation of learning and performance effects of drugs cannot rest on one task or one experiment. Overall, the evidence summarized in this paper provides strong support for the conclusion that drugs can and do enhance retention and that the effects are due to influences on memory storage rather than to other factors that influence performance. PMID- 2574072 TI - Increased susceptibility to inoculated Lewis lung carcinoma (3LL) but unaltered tumor growth in mice treated with monoclonal antibody to L3T4 on mouse T-helper cells. AB - The importance of different lymphocyte cell populations in early recognition and destruction of tumor cells has not been fully established. Certainly natural killer cells and cytotoxic T lymphocytes are involved. Using a recently developed monoclonal antibody (GK 1.5) that has been shown to have in vivo cytotoxic activity directed at L3T4-bearing T cells, we provide in these experiments evidence that T-helper cells are also important in early antitumor immunity. Development of progressive tumor growth after the subcutaneous inoculation of 10(5) Lewis lung carcinoma (3LL) cells was greater in antibody-treated mice (13 of 20 treated mice vs. 6 of 21 controls). Nevertheless, in those animals that developed tumors, the latentcy period (time from tumor cell inoculation until tumor first palpable) and tumor growth rate were no different in antibody-treated mice when compared with control animals. In subsequent experiments, animals were exposed to irradiated tumor cells in Freund's adjuvant on three occasions and tumor growth was then assessed. Growth was slower in the sensitized group. Administration of GK 1.5, however, did not enhance the tumor growth rates in either the previously sensitized or control groups. The results suggest that T helper cells might be of greater functional importance in early tumor cell recognition and destruction and of lesser importance in the restraint of tumor growth, once the tumor has become established. PMID- 2574074 TI - Effects of opiates during baroreceptor and ergoreceptor induced changes in blood pressure. AB - Various opioids were used to investigate the role they might play in the cardiovascular responses to fatiguing isometric contractions. Changes in blood pressure were measured in cats anaesthetised with alpha-chloralose. Fatiguing isometric contractions of the hind limb muscles (ergoreceptor activation) were generated using a microprocessor controlled stimulator (50 Hz, 0.2 ms, 200-800 mV). Baroreceptor inactivation was elicited by carotid artery occlusion. Muscle contraction caused an increase in mean arterial pressure of 51 (SEM 12) mm Hg and carotid occlusion an increase of 56(9) mm Hg above resting levels in control conditions. Injection of dynorphin (0.5-5.0 micrograms.5 microliters-1) into the cerebral aqueduct just rostral to the 4th ventricle eliminated the pressor response to muscular contraction (mean arterial pressure at rest, 80-118 mm Hg: on fatigue, 72-129 mm Hg) but did not affect the pressor response to carotid occlusion in the same cats. Similarly, injections of met-enkephalin (1-100 micrograms.5 microliters-1) or beta-endorphin (10-100 micrograms.5 microliters-1) eliminated the ergoreceptor induced changes in mean arterial pressure during isometric contractions but had no effect on the changes caused by carotid occlusion. Pressor responses to nerve crush were not eliminated. These results support the suggestion that a catecholaminergic-opioidergic pathway in part mediates the cardiovascular responses to ergoreceptor afferent but probably not baroreceptor afferent input. PMID- 2574073 TI - Sulfur-induced polioencephalomalacia in sheep: some biochemical changes. AB - The effect of high dietary sulfur (S) supplementation on blood thiamine (B1) concentration, biochemical indices of liver, muscle and kidney damage and selected plasma electrolytes was studied in six sheep. Three of these sheep received an additional 230 mg thiamine/kg diet (Group 2). After approximately 2.5 3 weeks on this diet, all three sheep in the non-B1-supplemented group (Group 1) showed loss of appetite and developed mild neurological signs: depression, intermittent signs of excitation and head pressing. Increases in blood B1 concentration and plasma creatine kinase (CK) and aspartate aminotransferase (AST) were observed during this time in all affected animals. Clinical signs lasted only for two to five days. Sheep in group 2 were clinically normal throughout the experiment, but all of these animals also had elevated blood B1 concentrations and plasma CK activity at the 3 wk sampling. Plasma magnesium concentrations of group 1 sheep were elevated at the 2.5-3 wk and 6 wk samplings but they declined significantly (p less than 0.05) to low normal levels thereafter. Magnesium concentrations of group 2 sheep were low at the beginning but progressively increased during the course of the experiment. At necropsy, brain lesions suggestive of polioencephalomalacia (PEM) were observed in all sheep but were most marked in group 1. It is speculated that PEM may be caused by a direct toxic effect of S, S metabolites or B1 antimetabolites in the brain rather than by an in vivo B1 deficiency per se. PMID- 2574075 TI - Role of alpha 1-adrenoceptor activity in progression of cardiac hypertrophy in guinea pig hearts with pressure overload. AB - To elucidate the role of alpha 1- and beta-adrenergic activities in pressure overload hypertrophy, changes of alpha 1- and beta-adrenoceptors were measured by radioligand binding assay, and the preventive effects of alpha 1- and beta adrenoceptor blockade on cardiac hypertrophy were assessed in guinea pigs after aortic banding. Five days after banding, dry weight of left ventricle had not increased, though wet weight increased due to marked intercellular oedema. In this period, the maximum binding capacity of [3H] prazosin increased to 31.1 (SEM 2.2) fmol.mg-1 from (sham operation) 17.0(2.1) fmol.mg protein-1, p less than 0.01, whereas the maximum binding capacity of [3H]dihydroalprenolol did not increase: 143(16) fmol.mg-1 (banded) v 153(13) fmol.mg-1 (sham). Three weeks after aortic banding, the maximum binding capacity of both ligands increased to 45.6(5.5) fmol.mg-1 and 232(21) fmol.mg-1, respectively, accompanied by a significant increase in left ventricular dry weight, from 0.46(0.02) mg.g-1 (sham) to 0.62(0.08) mg.g-1 (banded), p less than 0.01. Continuous subcutaneous administration of the alpha 1-blocker bunazosin (0.1 mg.kg-1.d-1) significantly attenuated the increase in left ventricular dry weight whereas the beta-blocker propranolol (5 mg.kg-1.d-1) did not: 0.55(0.03) v 0.66(0.04) mg.g-1 respectively, after 3 weeks. These results show that pressure overload elicited an increase in myocardial alpha 1-adrenoceptors before the onset of cardiac hypertrophy, and that an alpha 1-blocker could prevent the development of hypertrophy in the pressure overloaded heart. PMID- 2574077 TI - Tubular nephrotoxicity during long-term ifosfamide and mesna therapy. AB - The nephrotoxic effects of ifosfamide were assessed in 18 children and adolescents given cumulative doses of 32-112 g/m2 (1.6 g/m2 per day in sequential 5-day courses) with the uroprotectant mesna (1.2 g/m2 per day). Tubular nephrotoxicity was evaluated by measuring the urinary concentrations of N-acetyl beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and total protein before and during sequential courses of therapy. Of 15 patients who had normal levels of tubular markers before ifosfamide therapy, only 1 developed a persistent increase in baseline values of the three tubular markers with the sixth course of ifosfamide. Although transient increases in the excretion of these markers were observed during each 5-day course of ifosfamide, the magnitude did not increase over sequential courses in these 15 patients. Of the remaining three patients who had increased NAG levels before ifosfamide therapy, two showed a progressive increase in enzymuria and proteinuria, and serum creatinine concentrations increased in a single patient who had obstructive uropathy. Our data suggest that children with normal renal function can be given large cumulative amounts of ifosfamide in fractionated doses with little risk of progressive clinical nephrotoxicity. PMID- 2574076 TI - Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques. AB - Three transgenic mouse lines designated Tg 69, 71, and 81 were produced harboring a Syrian hamster (Ha) prion protein (PrP) gene; all expressed the cellular HaPrP isoform in their brains. Inoculation of Tg 81 mice or hamsters with Ha prions caused scrapie in integral of 75 days; nontransgenic control mice failed to develop scrapie after greater than 500 days. Tg 71 mice inoculated with Ha prions developed scrapie in integral of 170 days. Both Tg 71 and Tg 81 mice exhibited spongiform degeneration and reactive astrocytic gliosis, and they produced the scrapie HaPrP isoform in their brains. Tg 81 brains also showed HaPrP amyloid plaques characteristic of Ha scrapie and contained integral of 10(9) ID50 units of Ha prions based on Ha bioassays. Our findings argue that the PrP gene modulates scrapie susceptibility, incubation times, and neuropathology; furthermore, they demonstrate synthesis of infectious scrapie prions programmed by a recombinant DNA molecule. PMID- 2574078 TI - Biochemical characteristics of mouse mammary tissues, preneoplastic lesions and tumors. AB - A number of metabolizing systems are measured in normal, preneoplastic and neoplastic mouse mammary tissues derived under three different conditions. These biochemical functions are considered to be important in the activation and detoxification of carcinogens and other xenobiotics and have been linked to the process of rat liver hepatocarcinogenesis. The cytochrome P450-dependent enzyme aminopyrine N-demethylase, consistently depressed in hepatocarcinogenesis models in mouse and rat, does not show a significant change among normal, preneoplastic and neoplastic mammary tissues. Glutathione and the enzymes of glutathione metabolism and utilization (e.g. glutathione-S-transferases and gamma-glutamyl transferase), active in the detoxification of xenobiotics, show no significant differences in carcinogen-induced tumors or in their homologous preneoplasias compared to control tissue. There is no increase in the anionic glutathione-S transferase, a principal marker in rat hepatocarcinogenesis. The only observed biochemical change was a significant decrease in gamma-glutamyl cysteine synthetase the glutathione synthetic enzyme, in the carcinogen-induced preneoplastic and neoplastic line compared to control. Also inorganic glutathione peroxidase was lower in the preneoplastic, but not in the neoplastic tissues. PMID- 2574079 TI - Importance of hyperglucagonemia in eliciting the sepsis-induced increase in glucose production. AB - The plasma concentration of various catabolic hormones, including glucagon and catecholamines, is elevated in sepsis. Furthermore, the infusion of these hormones into control animals increases the rate of glucose production. Previous studies by our laboratory have demonstrated that adrenergic blockade alone is not able to reverse or prevent the sepsis-induced increase in glucose metabolism. Therefore, the purpose of the present study was to determine whether the sepsis induced hyperglucagonemia was important to maintain the elevation in glucose metabolism. Hypermetabolic sepsis was produced in chronically catheterized conscious rats by repeated subcutaneous injections of Escherichia coli. Glucose kinetics, assessed by the constant i.v. infusion of [6-3H]- and [U-14C]-glucose, were determined in septic and nonseptic rats prior to and for 3-4 hr after the infusion of somatostatin with or without insulin replacement. Sepsis increased the rate of glucose appearance (80%), recycling (276%), and metabolic clearance (88%), as well as the plasma lactate concentration (140%), compared to nonseptic rats. Lowering both the insulin and glucagon concentration with somatostatin did not attenuate the sepsis-induced increases in glucose metabolism. However, when the hyperglucagonemia was selectively reduced by replacing insulin, and euglycemia was maintained by a glucose infusion, the elevated rate of endogenous glucose production returned to levels not different from nonseptic animals. In contrast, the sepsis-induced elevation of glucose clearance was unaltered under these conditions. These results indicate that during hypermetabolic sepsis the elevated glucagon level is an important mediator of the enhanced rate of gluconeogenesis. PMID- 2574080 TI - [Changes in monoamine neurotransmitters in CSF during inhibition of defensive hypertensive reactions by inputs of deep peroneal nerve]. AB - Our previous work has indicated that excitation of hypothalamic defence area (HDA) could lead to an increase in the release of central monoamine neurotransmitters, pressor and other defence responses. The present experiments showed that stimulation of deep peroneal nerve with a current of low frequency and low intensity could inhibit the pressor, abolish the increase of noradrenaline and its metabolite MHPG and attenuate that of 5-HIAA (a 5-HT metabolite), dopamine and its metabolites DOPAC and HVA in CSF. The data suggest that inputs of deep peroneal nerve may inhibit the increased release of central monoamine neurotransmitters, and then defence reactions; and inhibition of NA release in some nuclei of the brain is an important mechanism of inhibition of defence pressor by inputs of deep peroneal nerve. PMID- 2574082 TI - Calcitonin gene-related peptide and calcitonin as tumour markers in MEN 2 family screening. AB - This investigation deals with the potential additional value of serum CGRP measurements as compared to calcitonin in screening for medullary carcinoma of the thyroid (MTC) in families with multiple endocrine neoplasia type 2 (MEN 2). Basal as well as pentagastrin-stimulated values for CGRP are evaluated in relation to the corresponding levels for calcitonin. Serum CGRP is within normal range in most family members with pathological calcitonin response to the pentagastrin stimulation test. Furthermore, these potentially affected family members do not respond to the pentagastrin stimulation test with an increase in CGRP. Pentagastrin stimulation tests performed in patients with manifest MTC affect the serum CGRP levels inconstantly and in two patients, with elevated basal level of CGRP, stimulation caused a release of calcitonin while concentrations of CGRP remained unaffected. We conclude that determination of serum CGRP adds no information to that of serum calcitonin in MEN 2 family screening for MTC. PMID- 2574081 TI - Effect of fenoldopam, a dopamine D-1 receptor agonist, on pituitary, gonadal and thyroid hormone secretion. AB - The influence of fenoldopam, a dopamine (DA) D-1 receptor agonist, on basal and GnRH/TRH stimulated PRL, GH, LH, TSH, testosterone and thyroid hormone secretion was studied in nine normal men. All men received 4-h infusions of either 0.9% saline or fenoldopam at an infusion rate of 0.5 microgram/kg min, 12-16 ml/h, adjusted according to weight. After 3 h of infusion, 50 micrograms GnRH and 100 micrograms TRH was given i.v. Blood samples were collected every 15 min from 1 h before to 1 h after the infusion for a total of 6 h for measurements of PRL, LH, FSH, GH, TSH, testosterone, T4 and T3. The median PRL concentration increased significantly (P less than 0.01) to 128%, range 87-287, of preinfusion levels, compared to the decline during control infusion (85%, 78-114). Basal TSH levels declined significantly to 71% (60-91) during fenoldopam compared with 82% (65 115) during control infusion (P less than 0.05). Basal LH, FSH, GH and thyroid hormones were similar during fenoldopam and control infusions (P greater than 0.05). The LH response to GnRH/TRH was significantly (P less than 0.02) increased by fenoldopam infusion. Basal and stimulated testosterone concentration was lower during fenoldopam (P less than 0.01) infusion compared with control. Other hormones were similar after GnRH/TRH stimulation during fenoldopam and saline infusions. These results suggest that DA D-1 receptors are involved in the modulation of pituitary hormone secretion. We suggest that the effect of fenoldopam on PRL and TSH is mainly at the hypothalamic level. Regarding the effect on LH concentrations, an additional direct effect of fenoldopam on testosterone regulation can not be excluded. PMID- 2574083 TI - Effect of subacute cabergoline treatment on prolactin, thyroid stimulating hormone and growth hormone response to simultaneous administration of thyrotrophin-releasing hormone and growth hormone-releasing hormone in hyperprolactinaemic women. AB - It is known that dopaminergic neurotransmission is involved in the control of PRL, TSH and GH secretion. Cabergoline (CAB) is a new ergolinic derivative with a long-acting dopaminergic activity. We evaluated 11 women with pathological hyperprolactinaemia before and during sub-acute CAB treatment (0.8-1.2 mg/p.o.; 8 weeks). Simultaneous administration of TRH (200 micrograms i.v.) and GHRH 1-44 (50 micrograms i.v.) were carried out before and after 4, 8 and 10 week intervals from the beginning of CAB treatment. Basal PRL levels (2453.5 +/- S.E. 444.5 mU/l) were significantly reduced during CAB administration (week 4: 164.5 +/- 66.5 mU/l; week 8: 168.0 +/- 66.5 mU/l; P less than 0.01) and no variations were observed 2 weeks after drug discontinuation (week 10: 210.0 +/- 98.0 mU/l). PRL percentage change after TRH was increased by CAB (P less than 0.05). No variation in basal and TRH-stimulated TSH levels was found during CAB administration. A slight increase in GH basal levels (3.0 +/- 0.6 mU/l) was found after weeks 4 (6.4 +/- 2.0 mU/l) and 10 (5.8 +/- 1.6 mU/l) (P less than 0.05). GH response to GHRH was significantly enhanced (ANOVA: P less than 0.01) during sub-acute CAB treatment. A positive correlation was found between GH secretory area and weeks of CAB therapy (P less than 0.01). Our data show that CAB is very effective in lowering PRL secretion in hyperprolactinaemia, and is able to modify PRL and GH responses after TRH and GHRH. The increasing trend in GH basal and GHRH stimulated GH levels seems to indicate that CAB can override the central dopaminergic tone which is operative in hyperprolactinaemia. PMID- 2574084 TI - The pituitary-adrenal response to CRF-41 is unaltered by intravenous somatostatin in normal subjects. AB - We have previously reported that the hypothalamo-pituitary-adrenal response to insulin-induced hypoglycaemia is normal while the cortisol release to pituitary stimulation by corticotrophin releasing factor (CRF-41) is reduced in obesity. Impaired growth hormone (GH) secretion is also found in obesity which may result from altered central levels of somatostatin (SMS). We have investigated, by giving a simultaneous infusion of SMS to six volunteer normal weight men during a CRF test, whether it is possible for SMS to modify pituitary-adrenal function. Each subject received intravenous CRF-41 (0.5 micrograms/kg) on two occasions during an infusion of isotonic saline or SMS (4 micrograms/min) in a randomized double-blind study. Plasma GH, cortisol, ACTH and SMS were measured. Three subjects demonstrated GH peaks during saline infusion but no peaks were seen in any subject during SMS infusion. No significant difference was found between peak cortisol responses during saline or SMS infusion (SMS cortisol 443 +/- 61 nmol/l, saline cortisol 485 +/- 52 nmol/l); neither was there any difference in the ACTH responses. We conclude that SMS does not alter the pituitary response to CRF in normal weight men and is thus less likely to be responsible for the altered pituitary-adrenal function seen in obesity. Further studies of alternative mechanisms are required to explain the cause of this abnormality. PMID- 2574085 TI - Prenatal diagnosis of alpha-1-antitrypsin deficiency using polymerase chain reaction (PCR). Comparison of conventional RFLP methods with PCR used in combination with allele specific oligonucleotides or RFLP analysis. AB - Prenatal diagnosis of alpha 1-antitrypsin (AAT) deficiency can be performed in the 1st trimester of pregnancy. These diagnoses have been based on DNA technology using either RFLP analysis or hybridization with allele specific oligonucleotides. Several RFLPs within and flanking the AAT gene have been found to render most families informative. The polymerase chain reaction allows specific DNA sequences to be amplified up to ten million fold. Both sequences containing a specific mutation or an RFLP can be amplified by this method. We have compared conventional RFLP methods with PCR used in combination with allele specific oligonucleotides or RFLP analysis, in a case of prenatal diagnosis of AAT deficiency of the ZZ type. PMID- 2574086 TI - Multipoint linkage mapping of the Xq25-q26 region in a family affected by the X linked lymphoproliferative syndrome. AB - We have performed, in a large Swiss family, a study of linkage between various DNA markers in the Xq24-27 region and the locus for the X-linked lymphoproliferative syndrome (XLP). Our results indicated that the marker DXS37 in Xq25-q26 is genetically linked to the XLP syndrome. The multipoint linkage analysis showed that the disease locus is distal to DXS11, but proximal to the hypoxanthine phosphoribosyl-transferase gene (HPRT). PMID- 2574087 TI - Immunologic studies in patients with Takayasu's arteritis. III. Immunoregulatory changes. AB - Study of cellular immune function in 14 patients with Takayasu's arteritis (TKA) revealed markedly decreased active E rosettes and CD4+ cells and slightly diminished CD8 + and autologous rosette-forming T cells. They were also found to have decreased production of interleukin-2 and decreased response to interleukin 1. Patients with active disease were also found to have decreased response to IL 2. Conversely, patients with inactive disease were found to have a normal response to interleukin-2. Patients with TKA, whether active or inactive, had normal production of interleukin-1, normal concanavalin-A-induced and spontaneously expanded suppression, normal NK cell function and normal enhancement of NK cell function by interleukin 2. The findings indicate that the immunoregulatory disturbance of TKA is different from that occurring in connective tissue disorders. PMID- 2574088 TI - Mechanism of action of colchicine. VI: Effect of colchicine on generation of leukotriene B4 by human polymorphonuclear leukocytes. AB - Three microtubule-disruptive agents (colchicine, oncodazole, and vinblastine) are shown to suppress ionophore A23187-induced generation of LTB4 in a dose-related manner. The slopes of the dose-response regression lines were similar for the three drugs. Trimethyl-colchicinic acid has no effect on LTB4 generation. The suppressive effect of colchicine (1 x 10(-6) M) can be blocked completely by taxol (1 x 10(-6) M) which promotes and stabilizes microtubule assembly. The data suggest that colchicine suppresses the generation of LTB4 via its effect on microtubules. PMID- 2574090 TI - Panting and acid-base regulation in heat stressed birds. AB - 1. Studies in respiratory physiology and acid-base balance of panting birds exposed to high Tas show that flying as well as nonflying birds can use the respiratory system simultaneously for gas exchange and evaporative cooling. 2. The present study proves that well acclimated hand-reared birds can effectively regulate a normal CO2 level and acid-base status in arterial blood, when exposed to extremely high temperatures (50-60 degrees C). 3. In many birds practising simple or "flush-out" panting, the dead space can be reduced to a volume which is estimated to be approx 15% the volume of the respiratory tract. 4. These two modes of ventilation, shallow and high-rate, restricted to the nonrespiratory surfaces, may ensure the avoidance of CO2-washout and limit lung ventilation to the volumes needed for oxygen consumption. 5. This view supports earlier theories, suggesting the existence of physiological shunt mechanisms which operate during thermal panting in birds. PMID- 2574089 TI - Pharmacokinetic-pharmacodynamic relationships of alpha-adrenoceptor antagonists. AB - Competitive alpha1-adrenoceptor antagonists are effective in the treatment of both hypertension and cardiac failure. Prazosin has both a short half-life and a short duration of action, but other related quinazoline derivatives, such as doxazosin and terazosin, have pharmacokinetic and pharmacodynamic profiles which make them potentially suitable for once-daily administration. Acute reductions in blood pressure have been correlated with plasma concentrations of prazosin but in most instances, particularly during long term therapy, there is no simple, direct relationship between drug concentration and the fall in blood pressure. Using integrated pharmacokinetic-pharmacodynamic analysis, correlations have been described not only for reductions in blood pressure during short and long term treatment but also for alpha1-adrenoceptor antagonist activity. Furthermore, this integrated approach defines the drug concentration-effect relationship in individual subjects and provides a mathematical description of response that is potentially useful for investigating the factors (both kinetic and dynamic) which influence the inter- and intrasubject variability in antihypertensive effect of alpha-adrenergic blockers. Preliminary data suggest that the long term response to treatment with prazosin and doxazosin is mainly dependent upon the height of the pretreatment blood pressure and the response to the first dose. PMID- 2574091 TI - Tissue blood content in anaesthetised sheep and horses. AB - The blood content of tissue in eight anaesthetized sheep and three anaesthetized horses was measured using chromium labelled autologous red blood cells. 2. Approximately half the total blood volume was found to be distributed within the body tissues and, with the exception of the spleen and fat, the distribution was similar in these two species. PMID- 2574092 TI - Corticotrigeminal motor pathway in the rat--II. Anterio- and retrograde HRP labeling. AB - 1. Horseradish peroxidase (HRP) injection into the rat cortical jaw motor area (JMA) disclosed direct projection fibers in and around the motor trigeminal nucleus (MTN), primarily contralaterally. 2. Descending axons were found in the ventromedial half of the cerebral peduncle and MTN-projecting axons were concentrated near the descending facial nerve root. 3. HRP injection into the peduncle could label 1257 cells in the JMA, 128 cells in the taste area and 1409 cells in the neck-forelimb motor area ipsilaterally. 4. Some MTN-terminated axons could be traced from the peduncle in serial sections. PMID- 2574093 TI - Ultradian and circadian CO2 emission variations in nocturnal and diurnal animals exposed to a light stimulus. AB - 1. Carbon dioxide emission (VCO2) has been continuously recorded in three laboratory animal species (Sprague-Dawley rats, Japanese quail, Hartley guinea pigs) which differ by their nocturnal and diurnal activities. A 100 lux stimulus has been delivered at various time intervals. 2. A regular alternation of 12, 3 or 1.5 hr light (L) and darkness (D) gives VCO2 circadian and ultradian rhythms of 24, 6 or 3 hr periods, respectively, in quail and rats. 3. Such circadian and ultradian LD rhythms are not induced in all guinea-pigs. 4. The amplitudes of the VCO2 responses are greatest at D----L when the animals have a maximum diurnal activity and at L----D when their maximum activity is nocturnal. 5. Interactions between circadian and ultradian rhythms are seen in all LD experiments, as well as in continuous light (LL) or continuous dark (DD). 6. No more well-marked or even inverted VCO2 responses to the light stimuli may occur after several days of exposure to these LD alternations. PMID- 2574094 TI - Effects of inhibition of thyroid function and of cold on melatonin synthesis and porphyrin content in the Harderian glands of male Syrian hamsters, Mesocricetus auratus. AB - 1. Indole metabolism and porphyrin content of the Harderian glands of the male Syrian hamster were measured as functions of drug-induced hypothyroidism and exposure to cold conditions. 2. Harderian gland N-acetyltransferase (NAT) activity was reduced from control levels by hypothyroidism induced by methimazole; exposure to cold had no effect on NAT activity. 3. Immunoreactive melatonin in the Harderian glands was unaffected by the state of thyroid secretion. However, immunoreactive melatonin content declined after 180 and 270 min, at 4 degrees C, suggesting that Harderian gland melatonin may be involved in thermoregulation. 4. Porphyrin content of the Harderian glands was not affected by either thyroid secretion or cold. PMID- 2574095 TI - Effects of diphenylamine-2-carboxylate on sodium and chloride transport across bovine tracheal epithelium: studies in monolayers and in the native tissue. AB - 1. The short-circuit current (I0) across monolayers of bovine tracheal epithelial cells is the sum of Na+ absorption and Cl- secretion. 2. Diphenylamine-2 carboxylate (DPC), added to the mucosal side of the native tissue or monolayers induced a rapid, dose-dependent and fully reversible reduction in I0, which reached zero with 3 mM DPC. 3. The blocking effect of DPC was examined during incubation (1) in standard, (2) in Cl(-)-free and (3) in Na+-free solution. Dose response curves revealed that the IC50 was not altered following ion substitution: it was approximately 0.7 mM DPC. 4. Thus, in bovine tracheal epithelium, DPC was an effective blocking agent of both Na+ and Cl- transport. PMID- 2574096 TI - Erythrocyte osmotic fragility and cation concentrations during experimentally induced bovine anaplasmosis. AB - 1. The osmotic fragility, the concentrations of Na, K and Ca, the osmolality and the total ATPase activity of bovine erythrocytes from uninfected and Anaplasma marginale-infected bovines were studied in an attempt to correlate these parameters with the decrease in the cellular ATP concentration reported during bovine anaplasmosis. 2. The osmotic fragility found in infected bovine erythrocytes, at 0.52% NaCl, was about two times greater than that observed in non-infected bovines. The increase in osmotic fragility was directly related to the increase in intra-erythrocytic parasitemia. 3. The decrease in ATP concentration reported during bovine anaplasmosis could not be directly related to the increased fragility of these cells. The artificial depletion of erythrocytic ATP did not reproduce the same alteration in the osmotic response to NaCl. 4. The plasmatic and cytoplasmatic concentrations of Na, K and CA did not change significantly during bovine anaplasmosis, whereas the interior of the erythrocytes became hyperosmolal. 5. A. marginale-infected bovine erythrocyte membranes showed an increased ATPase activity when compared to control bovines. Parasite-enriched fractions also presented ATPase activity. PMID- 2574097 TI - Sharing food in the stomachs of seabirds between adults and chicks--a case for delayed gastric emptying. AB - 1. Retention times of food in stomachs of breeding and non-breeding African pengiuns (Spheniscus demersus) were examined. 2. Rates of gastric emptying in non breeding birds were linearly related to the mass of food in the stomach. 3. Breeding birds returned to the nest with more food in their stomachs when chicks were larger. The rate of regurgitation of food was linearly related to chick mass. 4. Retention times of food in the stomachs of breeding penguins can only be explain by cognisance of observed regurgitation rates and by assuming that there is no gastric emptying through the pyloric sphincter. PMID- 2574098 TI - Comparative ultrastructure of maturing toad (Bufo ictericus) and rabbit (Oryctolagus cuniculus) erythroid cells with regard to hemoglobin biosynthesis. AB - 1. Toad and rabbit maturing erythroid cells were comparatively analysed with regard to their ultrastructural modifications involved in hemoglobin (Hb) biosynthesis. 2. The mitochondrial inner membrane differentiates to a lamellated body that, successively, gives rise to prehemosomal vesicles, prohemosomes, and to hemoglobinized organelles called hemosomes. 3. The prehemosomal vesicle involves ferruginous inclusions, taken as iron sources for heme biosynthesis, as well as the polypeptide globin chains, assembling themselves in the course of volume reduction. 4. From the prohemosomal stage onwards, where possibly heme biosynthesis occurs, hemosomes are formed; these organelles are presumably sites where the final Hb biosynthesis could take place. 5. All development stages leading to hemosome formation are similar in toad and rabbit erythroid cells, except that, in the toad, the structural prohemosome characteristics persist in hemosomes. 6. Through toad erythroid cell fractionation and electrophoresis of the organelle lysate supernatant, a wide and a weak cytoplasmic Hb bands were obtained; the latter coincides with the intraorganellar Hb band. PMID- 2574099 TI - Vecuronium infusions for prolonged muscle relaxation in the intensive care unit. AB - Neuromuscular blockade by vecuronium infusion is described in 13 patients requiring ventilation in an ICU for periods of 15 to 68 h. A loading dose of vecuronium (0.1 mg/kg) was given, followed by continuous infusion adjusted to maintain approximately 90% block as assessed by the presence of one response to a Train-of-Four stimulation. The average infusion rate was 0.103 mg/kg.h. The average time to complete recovery of myoneural function, as assessed by an obviously sustained response to tetanic stimulation, after the termination of the vecuronium infusion was 28 min. There were no adverse cardiovascular or toxic effects noted as a result of vecuronium administration. Vecuronium administered by infusion produced satisfactory neuromuscular relaxation in patients requiring ventilation in the ICU. PMID- 2574100 TI - Selective sensitive period in chick embryo: toxic effect of exogenous neurotransmitters. AB - The phenomenon of sudden mortality in the chick embryo, induced by the exogenous neurotransmitters norepinephrine, epinephrine, dopamine, serotonin, carbachol, and by the beta-blockers propranolol and atenolol, is described. When introduced singly into eggs (albumen) in doses of 0.1 mg per egg, these substances induced highly significant, sharply increased mortality (60% to 100%) when the introduction was on embryonic (incubation) days 8 to 12 (hereafter called E8 and E12), but none if introduction was earlier. These ages follow the appearance of functional receptors (or receptor-effectors) for these substances. However, the involvement of receptors here has not been proved. Solvent alone (Ringer's solution for chick) had no effect, indicating that the procedures used were in themselves not lethal. Possibly, the above neurotransmitters became lethal to the embryo because they were introduced in excess of the amounts which were produced and needed at that time by the embryo for optimal development. PMID- 2574102 TI - [Neurotensin, dopamine and mode of action of neuroleptics]. AB - It has new been almost ten years since interactions between the neurotensinergic and dopaminergic neuronal systems were first described. These results have now been confirmed on anatomical and biochemical as well as on behavioural grounds. First, we describe experiments showing that ascending dopaminergic pathways control the density of neurotensinergic binding sites in structures such as prefrontal cortex, nucleus accumbens and striatum. Secondly, we attempt to elucidate the consequences that such receptor hetero-regulations, together with the presence of mixed neurotensin/dopamine fibers in the prefrontal cortex, might have on the mode of action of neuroleptic drugs. Indeed, by blocking dopamine receptors, neuroleptics might bring about long-term and heterogeneous changes in the transmission of non dopaminergic systems in those projection areas possessing dopamine receptors. The new functional hierarchies thus produced between dopamine innervated structures might then explain the therapeutic action of neuroleptics. PMID- 2574101 TI - [Treatment of negative symptoms in schizophrenia with neuroleptics]. AB - Different concepts of negative symptoms in schizophrenia are reviewed. The beneficial effects of neuroleptics are discussed. The results of a pharmacokinetic and pharmacodynamic study with Amisulpride in healthy volunteers are reported. Preliminary findings of a study with Amisulpride in schizophrenic patients with predominately negative symptoms are presented. The utility of various rating scales for documenting the clinical state of these patients during therapy, and correlations of negative symptoms with psychometric and psychophysiological data are discussed. Finally, therapeutic consequences suggested by different hypothesized etiological factors causing negative symptoms are considered. PMID- 2574103 TI - [Tardive dyskinesia. After more than 2 decades]. AB - The clinical aspects of tardive dyskinesia are describe, outlining the difficulties and the limits encountered by the clinician. The tools for its evaluation are reviewed, as well the epidemiology data and the current neuropathological hypothesis. PMID- 2574104 TI - Behaviour of transglutaminase activity in intestine of starved and refed rats. AB - Starvation causes an intestinal mucosa atrophy which is greater in jejunum than in ileum. Hypoplasia is promptly reversed by refeeding. Transglutaminase (TG) has been controversially implicated in cell proliferation and its role in intestine is not defined. We investigate, by the above described model, the behaviour of TG in proximal and distal small bowel as well as in colon of rats after 4 days of starvation and at day 1, 2, 3, 4, 5, 7 and 10 of refeeding. Our results emphasize a significative reduction of TG in small bowel induced by starvation (day 0) and a prompt recovery of the enzyme activity after refeeding; furthermore, in the first intestinal tract TG activity reaches from day 2 to day 5 values which are significantly higher than basal. Four days of starvation do not affect TG in colon. In conclusion, our study demonstrates that in rats high values of TG activity are coincident with the intense proliferative phase in small intestine subsequent to starvation atrophy. PMID- 2574105 TI - Beta-hexosaminidase activity in alcoholic fatty liver and in CCl4-induced liver fibrosis of the rat. AB - beta-Hexosaminidase (Hex) activity was previously found to be increased in the sera of patients with liver cirrhosis, cholestasis and acute alcohol intoxication, as well as in rats with CCl4-induced liver cirrhosis. We studied this enzymatic activity in the sera and liver tissue of rats with alcoholic fatty liver due to prolonged alcohol intake and CCl4-induced liver fibrosis in association with moderate alterations in liver function tests. Serum and liver Hex activity did not show any significant change in both experimental models. These data suggest that Hex is not an alcohol-induced enzyme, and that severe, but not moderate, liver damage can determine the increase in this lysosomal enzymatic activity. PMID- 2574107 TI - The stoichiometry of the tightly bound NAD+ in urocanase. Separation and characterization of fully active and inhibited forms of the enzyme. AB - 1. Urocanase, purified by classical methods [Keul, V., Kaeppeli, F., Ghosh, C., Krebs, T., Robinson, J. A. and Retey, J. (1979) J. Biol. Chem. 254, 843-851] from Pseudomonas putida was submitted to high-performance liquid chromatography on a TSK-DEAE column. The enzyme was eluted in three resolved peaks (A, B and C) exhibiting specific activities of 3.4 U/mg, 1.85 U/mg and 0.4 U/mg, respectively. 2. The difference spectra of peaks B and A as well as of C and A showed maxima at 330 nm. 3. Irradiation of peaks B and C at 320 nm resulted in an increase of urocanase activity by 45% and 400%, respectively. Peak A could not be photoactivated. Rechromatography of the photoactivated peaks B and C on the TSK DEAE column confirmed their partial transformation into peak A. 4. Spectroscopic methods for quantitative protein determination were adapted to urocanase. The stoichiometry of bound NAD+/urocanase (form A) was determined to be 1.75 by enzymic analysis of the free NAD+ released upon acid denaturation of the holoenzyme. A similar stoichiometry (1.8-1.9) was found for all three forms (A, B and C) by biosynthetic incorporation of [7-14C]nicotinate into urocanase using a nicotinate auxotrophic mutant of P. putida. 5. Form A of urocanase showed, after treatment with NaBH4 up to 50% inhibition, an elution pattern (TSK-DEAE column) similar to a mixture of forms A, B and C in the approximate ratio of 1:2:1. None of these forms could be photoactivated. 6. We conclude that form A of the urocanase dimer contains two intact NAD+ molecules. In form B one of the two subunits contains an NAD+-nucleophile adduct which is present in both subunits of form C. Full urocanase activity requires intact NAD+ in both subunits. Intact NAD+ can be regenerated from the adduct but not from the reduced form by photolysis. The two subunits of urocanase are independent both in their catalytic activity and in modification reactions. PMID- 2574106 TI - Coordinate action of a proximal homeoprotein binding site and a distal sequence confers the Ultrabithorax expression pattern in the visceral mesoderm. AB - Spatially regulated expression of the homeotic gene Ultrabithorax (Ubx) in the visceral mesoderm can be mimicked in transformed Drosophila embryos by expression of a Ubx--beta-galactosidase fusion gene. Here we show that a proximal homeoprotien binding sequence downstream of the Ubx transcription start site, the B element, is required for this pattern. A distal upstream Ubx sequence, but not the B element, is sufficient to confer the pattern if linked to an hsp70 TATA box in a heterologous construct. The pattern in this case requires Ubx function, like endogenous Ubx expression in the visceral mesoderm, suggesting that the distal upstream sequence contains an important target sequence for autoregulation. We propose that the B element, in the context of the Ubx promoter, functions to mediate enhancer function of the distal sequence. Thus, the visceral mesoderm pattern requires coordinate action of a proximal and a distal regulatory element. PMID- 2574108 TI - Clinical efficacy of xamoterol, a beta 1-adrenoceptor partial agonist, in mild to moderate heart failure. U.K. Xamoterol Study Group. AB - The clinical efficacy of xamoterol, alpha beta 1-adrenoceptor partial agonist, was determined in a multicentre double-blind, randomized, parallel group study of 240 patients with mild to moderate heart failure. At entry, 62% of patients were receiving diuretics (thiazides, or loop diuretics at a dose no greater than the equivalent of 80 mg of frusemide); 32% were taking nitrate formulations and 14% digoxin for control of atrial fibrillation. Assessments were carried out after a 1-week placebo run-in and after 3 months of treatment with either xamoterol or placebo. 198 patients completed the study of whom 186 had valid exercise tests. Mean exercise duration increased by 7% after placebo and by 19% after xamoterol during a progressive treadmill exercise protocol. Xamoterol significantly reduced peak exercise heart rate compared with placebo. Subjectively, there was improvement in breathlessness on the visual analogue scale after treatment with xamoterol compared with placebo, but no change in fatigue. We conclude that xamoterol produces sustained improvement in symptoms and exercise duration in mild to moderate heart failure. PMID- 2574110 TI - Postpubertal cryptorchism. Morphofunctional study with special reference to Leydig's cells. AB - In a group of 17 patients of postpubertal age with unilateral (n = 15) or bilateral (n = 2) cryptorchism, a significant decrease in the tubular diameter was observed, in addition to Leydig cell hyperplasia (many with cytoplasm vacuolization and/or atrophy) in both the cryptorchid testes and in the contralateral scrotal testes. The number of testosterone-positive Leydig cells in testicular tissue sections, studied with peroxidase-antiperoxidase, was diminished in the cryptorchid testes, whereas in the contralateral scrotal testes it was similar to the control group. Together with normal testosterone levels and elevated luteinizing hormone and follicle-stimulating hormone levels in peripheral blood, this leads us to think of a compensated dysfunction of the Leydig cells. This possible lower testosterone production by the Leydig cells in the cryptorchid testis is not borne out morphologically, where the volume of the organelles is similar to the contralateral scrotal testes. PMID- 2574109 TI - Dependence of hydrogen peroxide formation in rat liver microsomes on the molecular structure of cytochrome P-450 substrates: a study with barbiturates and beta-adrenoceptor antagonists. AB - In the present study, the molecular structure of xenobiotics has been successfully linked to their effect on the oxidase activity of cytochrome P-450, determined as microsomal hydrogen peroxide formation. A homologous series of 5 alkyl-5-ethyl barbiturates and a heterologous series of beta-adrenoceptor antagonists was used. The logarithm of the rate of microsomal hydrogen peroxide formation could be correlated with the logarithm of the apparent partition (n octanol/buffer) coefficient for the barbiturate derivatives according to a parabolic function. The statistics of the correlation improved considerably by applying a bilinear model in order to fit the data. This probably indicates that both transport of the substrate to cytochrome P-450 and interaction with hydrophobic substrate binding sites of cytochrome P-450 are involved in the modulating effect of substrates on the oxidase function of cytochrome P-450. With the series of beta-adrenoceptor antagonists no clear-cut structure activity relationship with regard to the oxidase activity was apparent at first sight. However, when the inhibitory effect of the beta-antagonists on the 'cytochrome P 450 metabolic intermediate (MI) complex' formation that occurs during the microsomal biotransformation of 33 microM tofenacine was studied a relationship with the lipophilicity could be demonstrated. It is known that MI complex formation occurs with specific subforms of cytochrome P-450. By using this inhibitory activity of the beta-adrenoceptor antagonists, the interaction of the compounds becomes restricted to these specific subforms of cytochrome P-450. In both the oxidase activity as well as the MI complex formation phenobarbital induced cytochrome P-450 is involved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574111 TI - Plasma protein binding of alpidem in healthy volunteers, in neonates and in liver or renal insufficiency. AB - The binding of alpidem, a new anxiolytic drug, has been studied in plasma from 6 healthy subjects, 12 patients with renal failure, 12 patients with liver cirrhosis and 12 chronic uraemics maintained on haemodialysis, as well as in 12 serum samples from the placental cord, to represent the situation in the newborn. The unbound fraction was 0.61% (healthy volunteers), 1.31% (newborns), 0.86% (cirrhotic patients), 0.72 (patients with renal failure), 0.70% (before haemodialysis) and 0.79% (after haemodialysis). Binding in the volunteers was significantly different from that in neonates and cirrhotics only. Alpidem became bound to isolated albumin (45 g.l-1) and alpha 1-acid glycoprotein (0.75 g.l-1) to 97.2% and 97.1%, respectively. The bound fraction of the drug in a mixture of two proteins was 99.1%. For alpidem, it appears that alpha 1-acid glycoprotein may balance the effect of any decrease in the albumin concentration. PMID- 2574112 TI - Electrophysiological studies with a 2,3-benzodiazepine muscle relaxant: GYKI 52466. AB - The effects of GYKI 52466, a new 2,3-benzodiazepine with muscle relaxant and anticonvulsant properties, were investigated and compared to those of midazolam in electrophysiological experiments. The effects of the drugs on the reflex potentials evoked by afferent nerve stimulation and recorded from the spinal roots in unanesthetized spinal cats were studied. GYKI 52466 exerted a strong inhibitory effect on the monosynaptic as well as the polysynaptic ventral root reflexes, while the dorsal root responses decreased slightly. In contrast, midazolam markedly enhanced the dorsal root responses, did not modify the monosynaptic reflex and partially inhibited the polysynaptic reflex. The spontaneous firing of cerebellar Purkinje cells was depressed by midazolam, but not by GYKI 52466. These results suggest strongly that, contrary to the classical 1,4-benzodiazepines, potentiation of the GABA-A receptor-mediated inhibition does not play a significant role in the pharmacological actions of GYKI 52466. PMID- 2574113 TI - Brain-specific expression of transthyretin mRNA as revealed by cDNA cloning from brain. AB - cDNAs for rat transthyretin mRNA were cloned from a brain cDNA library. Sequencing analyses showed the presence of an additional 5' sequence that had not been reported for the liver mRNA corresponding to the flanking promoter region of the gene. This additional sequence was expressed only in the brain, suggesting the presence of a brain-specific promoter. PMID- 2574114 TI - Retinoic acid controls expression of epidermal transglutaminase at the pre translational level. AB - Human epidermal keratinocytes were cultured until sub-confluence in low Ca2+ (0.15 mM) serum-free synthetic MCDB 153 medium. Raising the Ca2+ concentration to 1.15 mM caused an increase in envelope competence as well as plasma membrane associated transglutaminase (TGm) activity. This increase was not observed when the high Ca2+ medium contained retinoic acid. Immunofluorescence studies as well as immunoblotting with the TGm-specific monoclonal antibody B.C1 revealed that retinoic acid inhibits expression of TGm. Isolation and in vitro translation of mRNA with subsequent immunoprecipitation showed that retinoic acid inhibits TGm expression at the pretranslational level. PMID- 2574116 TI - Long-term follow-up of patients with Graves' orbitopathy treated by plasmapheresis and immunosuppression. PMID- 2574115 TI - Quantitative time course study of the skin response to histamine and the effect of H1 blockers. A 3-week crossover double-blind comparative trial of cetirizine and terfenadine. AB - A controlled, randomized, double-blind, crossover study was performed in 10 healthy volunteers to compare changes of cutaneous blood flow values (CBFV) determined by laser Doppler flowmetry before and after intake of a capsule containing either 10 mg cetirizine or 60 mg terfenadine. After the determination of the initial response to the anti-H1 agents, drugs were taken daily (cetirizine 10 mg, terfenadine 120 mg) over a 3-week period and the cutaneous response to histamine and saline was evaluated weekly, exactly 4 h after the last drug intake. The following significant variations were observed (analysis of variance for repeated measurements, p less than 0.05): (1) there is a decrease of histamine-induced wheal and flare under antihistamines (anti-H1), cetirizine being more potent than terfenadine; (2) CBFV, measured on the usual flare area, i.e. at 1 cm of the site of agonist injection, decreased after drug intake. There was a gradual increase of the CBFV inhibition over the 3-week follow-up, cetirizine being more effective than terfenadine, and (3) at the site of agonist injection, reduction of the edematous wheal was associated with significant increases of CBFV after drug intake. This quantitative pharmacologic in vivo assay on the agonist action indicates that at lower doses, cetirizine has a significantly higher anti-H1 activity than terfenadine and that this effect is maintained over a 3-week period. There was no tachyphylaxis. PMID- 2574117 TI - Thyroid-stimulating and eye muscle antibodies in Graves' disease and Graves' orbitopathy. PMID- 2574118 TI - A single major gene controls most of the difference in susceptibility to streptozotocin-induced diabetes between C57BL/6J and C3H/HeJ mice. AB - To assess genetic factors determining sensitivity to streptozotocin-induced diabetes in inbred strains of mice, a genetic analysis of streptozotocin sensitive C57BL/6J and streptozotocin-resistant C3H/HeJ mice was performed. One week after a single dose of streptozotocin (200 mg/kg body weight), differences in plasma glucose concentration were marked between male mice of the C57BL/6J and C3H/HeJ strains (p less than 0.001). To determine the number of genes responsible for the difference, F1 male progeny of a cross between parental strains were produced, and found to be streptozotocin resistant like C3H/HeJ parents. F1 mice were, therefore, backcrossed with streptozotocin-sensitive C57BL/6J mice (Backcross: F1 female female X C57BL/6J male male). The plasma glucoses of backcrossed male mice (n = 41) following streptozotocin treatment appeared to segregate into two populations, half like the C57BL/6J parent, and half like the F1 parent. Statistical analysis of the data revealed that the data fit a model with two distributions better than one with a single distribution, suggesting a single major gene responsible for the difference in streptozotocin susceptibility. This hypothesis was also supported by the observation that streptozotocin sensitivity in 12 recombinant inbred strains of C57BL/6J and C3H/HeJ mice appeared to segregate into two classes. Resistance to streptozotocin induced diabetes in F1 mice suggested that the expression of this gene is recessive, although X-chromosome linked inheritance could not be excluded. Efforts to map the streptozotocin-sensitivity gene revealed lack of right linkage to several loci including the H-2 locus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574119 TI - P-glycoprotein: multidrug-resistance and a superfamily of membrane-associated transport proteins. AB - The study of multidrug resistance (MDR) in tumor cell lines has led to the discovery of the plasma membrane P-glycoprotein (Pgp) molecule. This protein functions as an energy-dependent pump for the efflux of diverse anticancer drugs from MDR cells. It now appears that Pgp-mediated MDR tumor cells do occur in human cancers, and that they are likely to play a role in the ultimate response of patients to chemotherapy. Chemosensitizers, compounds able to reverse the MDR phenotype, have been identified and offer the exciting possibility of improving efficacy for some nonresponsive malignancies. Surprisingly, Pgp-like molecules can be found in evolutionarily distant species among both eukaryotes and prokaryotes. As a group, these proteins form a superfamily of ATP-dependent transport proteins. This finding has broad implications and provides new insights into how living organisms use this fundamental transport system to regulate the trafficking of diverse molecules across biological membranes. PMID- 2574120 TI - Antagonism by glucocorticoids and exercise on expression of glutamine synthetase in skeletal muscle. AB - Chronic glucocorticoid treatment results in skeletal muscle wasting. However, if the contractile activity of muscle is increased, this effect is abated. Because the gene encoding glutamine synthetase is known to be glucocorticoid inducible, it represents an appropriate model for testing whether glucocorticoids and endurance training can exert antagonistic effects on the expression of specific genes in muscle tissue. Our data confirm that administration of hydrocortisone 21 acetate to rats produces 2.4- and 5.9-fold increases in plantaris muscle glutamine synthetase enzyme activity and mRNA, respectively. Moreover, subjecting rats to a 12- to 16-wk exercise program diminishes the basal levels of these indices of glutamine synthetase expression to approximately 60% of the values observed in sedentary controls. Endurance training produces a similar effect on plantaris muscle glutamine synthetase expression in glucocorticoid-treated animals. These data demonstrate that the therapeutic effects of exercise in counteracting muscle atrophy are associated with attenuation of expression of a glucocorticoid-inducible gene in skeletal muscle. PMID- 2574121 TI - [Hepatic gamma-glutamyl transpeptidase]. PMID- 2574122 TI - [Idiopathic portal hypertension associated with connective tissue disease similar to systemic lupus erythematosus]. AB - A case of idiopathic portal hypertension associated with connective disease resembling systemic lupus erythematosus is described. The patient was a 50-year old woman with splenomegaly, ascites, esophageal varices, and pancytopenia, but without extrahepatic portal obstruction or cirrhosis of the liver. Electron microscopy of the liver showed perisinusoidal fibrosis. High titers of autoantibodies against proliferating cell nuclear antigen (PCNA) were found in the sera as well as in ascites; anti-DNA antibodies appeared after anti-PCNA antibodies and remained thereafter at a moderate titer. The possibility of an immunological process in the pathogenesis of idiopathic portal hypertension is discussed. PMID- 2574123 TI - Atenolol, bufuralol and prizidilol are dual antagonists of the responses of the electrically driven rat right ventricle strip to isoprenaline. AB - 1. Procaine, a membrane stabilizer, depresses the maximal responses of the electrically driven rat right ventricle to isoprenaline. 2. Esmomol is a competitive beta-adrenoceptor antagonist as it causes parallel rightward shifts of isoprenaline response curves. 3. Atenolol, bufuralol and prizidilol were dual antagonists of the responses to isoprenaline. 4. The competitive component of the dual antagonism (parallel rightward shift of response curve) is due to beta adrenoceptor antagonism whereas the noncompetitive component (depression of isoprenaline maximal response) is probably due to membrane stabilization. 5. This membrane stabilizing activity of beta-adrenoceptor antagonists may be clinically relevant. PMID- 2574124 TI - Involvement of GABAA receptor sites in diazepam hypothermia. AB - 1. Intraperitoneal (i.p.) injection of diazepam (1.5-6 mg/kg) decreased the core body temperature (BT) of the rats. The effect was dose-dependent. 2. The hypothermia produced by diazepam (6 mg/kg, i.p.) was decreased in animals pretreated with high doses of bicuculline (BIC, 3 mg/kg, i.p.), while low doses of BIC (1.5 mg/kg, i.p.) potentiated the hypothermia. 3. Picrotoxin (PIC, 1 and 2 mg/kg, i.p.) pretreatment also decreased the hypothermic effect of diazepam. 4. Pretreatment of animals with atropine (AT, 10 mg/kg, i.p.) or propranolol (PRO, 10 mg/kg, i.p.) potentiated the hypothermic response of diazepam. Phenoxybenzamine (PHEN, 0.5 mg/kg, i.p.), methergoline (METH, 0.5 mg/kg, i.p.) or pimozide (PIM, 0.5 mg/kg, i.p.) did not change the diazepam hypothermia. 5. Single administration of BIC, PIC, PRO, PIM or METH also induced hypothermia. 6. One can postulate that diazepam hypothermia may be induced through GABAA receptor sites. However, further studies will clarify this hypothesis. PMID- 2574125 TI - Comparative immunohistochemical study of the gastroenteropancreatic endocrine system of three reptiles. AB - The gastroenteropancreatic (GEP) endocrine system of three reptiles, Testudo graeca, Mauremys caspica, and Lacerta lepida, was investigated by means of immunocytochemistry. Single and double immunostaining methods have demonstrated immunoreactivity for insulin, glucagon, pancreatic polypeptide (PP), somatostatin, serotonin, and peptide tyrosine tyrosine (PYY) in endocrine cells of the pancreas of the reptiles studied. Islet-like structures with insulin immunoreactive (IR) cells surrounded by glucagon-IR cells were observed only in the splenic portion of the pancreas of M. caspica. Occasionally, somatostatin- and PP-IR cells were associated with glucagon-containing cells. Endocrine cells were also observed in the excretory ducts of the exocrine glands. Serotonin, bombesin, neurotensin, gastrin, glucagon, somatostatin, PYY, and insulin were demonstrated immunocytochemically in open-type GEP cells of the digestive tract of the animals studied. Serotonin, somatostatin, and glucagon-immunoreactive cells were the most abundant endocrine cell types. In L. lepida, PP- and peptide tyrosine tyrosine-immunoreactive cells were also frequently observed. Cells containing cholecystokinin, gastric inhibitory peptide, met- and leu-enkephalin, motilin, secretin, and vasoactive intestinal peptide could not be detected. The present work demonstrates that the reptilian GEP endocrine system is a complex structure containing most of the regulatory peptides similar in structure to those found in higher vertebrates. PMID- 2574126 TI - Thyroid function in sex-linked and autosomal dwarf chickens. AB - Thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) elevated plasma thyroxine (T4) and triiodothyronine (T3) concentrations in a (euthyroid) control line of chickens and in an autosomal dwarf strain. These agents were ineffective in sex-linked dwarf (SLD) chickens. Similarly, while somatostatin (SRIF) lowered plasma T4 and T3 concentrations in autosomal dwarf (ADW) chickens and controls, it had no inhibitory effect in the SLD strain. These results suggest that an impairment in the hypothalamus-pituitary-thyroid axis is at least partly responsible for hypothyroidism in the SLD strain. PMID- 2574127 TI - Increased risk for gestational diabetes mellitus associated with insulin receptor and insulin-like growth factor II restriction fragment length polymorphisms. AB - Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition during pregnancy. We have examined restriction fragment length polymorphisms (RFLPs) near "candidate diabetogenic genes" as one approach to identify molecular markers for GDM genes. Genotypes for insulin hypervariable region (HVR), insulin-like growth factor II (IGF2), insulin receptor (INSR), and glucose transporter (GLUT1) RFLPs were studied in 96 GDM and 164 control subjects, matched to GDM for race, age, and gravidity. Logistic regression analysis was used to explore the relationship between genotypes at these candidate gene loci and GDM, while adjusting for the effects of potential confounding variables. Among black subjects, the INSR allele 1 (P = 0.001) and interactions between INSR allele 1 with body mass index (BMI) (P = 0.002) and history of DM in subject's mother (P = 0.004) contributed significantly to GDM risk. Among Caucasian subjects, a similar relationship between the INSR allele 1 (P = 0.007) and INSR allele 1-BMI interactions (P = 0.011) on GDM risk were observed. In Caucasians, an additional significant risk factor was determined by an INSR allele 1-IGF2 allele 2 interaction (P = 0.018). No risk factors were identified in Hispanic subjects. These data continue to support the hypothesis that GDM is a heterogeneous disorder with respect to phenotypic and genotypic features. Furthermore, our data suggest that risk for GDM in black and Caucasian subjects is not due to obesity perse but to interactions between obesity and INSR alleles. In Caucasian women, INSR and IGF2 alleles interact to confer additional risk for GDM. Thus genes underlying susceptibility to GDM in some women may be similar to genes conferring risk to NIDDM, while in others novel genes may contribute to GDM risk. PMID- 2574128 TI - A rapid protocol for the purification of mitochondrial DNA suitable for studying restriction fragment length polymorphisms. AB - When analyzing mitochondrial DNA (mtDNA) from various normal and malignant human tissues, it became necessary to enhance mtDNA isolation for improved yields and quality. The method described here consists of rapid and simple-to-perform steps, avoiding complicated instrumentation. It was designed for preparation of undegraded mtDNA and is highly useful when limited amounts of tissues, cells and unique biopsies of tumors (fresh or frozen) are available. The resulting mtDNA is sufficiently pure for restriction analysis, subcloning, labeling and various types of hybridization. Using Sau3A and MspI, restriction analysis revealed new restriction-fragment length polymorphisms for Caucasians, independent of the DNA source, and hence excluding tissue-specific DNA modifications. PMID- 2574129 TI - Sequence variability of satellite DNA from the mealworm Tenebrio molitor. AB - To determine the consensus sequence of a 142-bp-long satellite monomer from the mealworm Tenebrio molitor, 22 clones were sequenced. Only nucleotide (nt) substitutions were found. The average sequence variability is 2.5 nt per monomer; changes are predominantly C----T and G----A transitions and the sequence tends to become A + T-rich. T. molitor satellite DNA is undermethylated and transcriptionally inactive. PMID- 2574130 TI - Nucleotide sequences of highly repetitive DNA from scleractinian corals. AB - The staghorn coral genome contains 5% of a satellite DNA, consisting of 80 to 300 x 10(3) copies of a 118-bp repeat unit per haploid Acropora genome. PMID- 2574131 TI - [Hygienic problems of the organization of work places using video display terminals]. PMID- 2574132 TI - [A physiologic hygiene assessment of the work of female telephone operators at a city directory-information service while working with display terminals]. AB - Physiologic and hygienic characteristics of body functioning state of female telephone operators working with displays in the inquiry information service "09" are presented. Insignificant changes of the cardiovascular system and functional state of the central nervous and neuromuscular systems have been detected along with the deterioration of visual function. The above changes are associated with neuroemotional stress during the work with video terminals and testify to distinct, sometimes quite significant fatigue. The necessity for optimization of work load and work organization of telephone operators by means of the development and introduction of rational work/rest regimes is set forth. PMID- 2574133 TI - [The humoral regulatory systems in thromboembolism of the pulmonary arteries]. AB - The work deals with the results of biochemical and angiographic studies in 26 patients with thromboembolism of the pulmonary arteries (TEPA) and pulmonary hypertension of various degree. Acute occlusion of the pulmonary arterial channel calls forth a response of the organism's humoral regulating systems. The degree of hypertension of pulmonary circulation in TEPA, which is determined by the volume of affection of the pulmonary vascular channel, is directly dependent on the functional activity of the adaptation system and the severity of disorders of the intra- and intersystemic connections. PMID- 2574134 TI - [Prenatal diagnosis of hereditary hemoglobinopathies]. PMID- 2574135 TI - [Screening for hemoglobinopathy performed for prenatal diagnosis]. PMID- 2574136 TI - [Use of recombinant hematopoietic growth factors after chemotherapy and high-dose chemo-radiotherapy]. PMID- 2574138 TI - Motor phenomena in benzodiazepine withdrawal. AB - Chronic use of benzodiazepines, the most widely prescribed of all psychotropic medicines, may lead to severe symptoms of withdrawal when the drugs are discontinued. The authors describe two cases of benzodiazepine withdrawal accompanied by unusual muscle activity. The neurologic mechanism for the motor abnormalities appears to be marked disinhibition of subcortical motor areas normally inhibited by gamma-aminobutyric acid. The motor phenomena may persist long after the more common signs of withdrawal have resolved and, if unrecognized, can lead to such misdiagnoses as drug seeking, conversion, hysteria, or malingering. PMID- 2574137 TI - Time course of hormonal effects on acetyl-CoA carboxylase as measured in digitonin-permeabilized rat hepatocytes. AB - Acetyl-CoA carboxylase activity was measured in digitonin-permeabilized rat hepatocytes by coupling the carboxylase reaction to the fatty acid synthase reaction. Using this assay the activity of acetyl-CoA carboxylase was covariant with the rate of fatty acid synthesis. Insulin and the tumor promotor phorbol myristate acetate were found to stimulate, and glucagon and noradrenaline to inhibit both cellular parameters. The stimulation of acetyl-CoA carboxylase by insulin developed slowly (15 to 30 min) whereas the phorbol myristate acetate effect developed faster (within 15 min). The inhibition of the enzyme caused by glucagon was already apparent within 1 min after hormone addition. Inhibition by noradrenaline, in the presence of propranolol, was also quite rapid and occurred within 2 min after addition of the agonist. PMID- 2574139 TI - Short synthetic oligonucleotide repeats detect human genomic variation. AB - We used synthetic oligonucleotide DNA probes specific for the four-base repetitive core sequences (GACA)n and (AGGC)n to examine human genomic variation. The results of hybridizing these oligonucleotides to human genomic digests indicate that they are useful and accessible markers for ubiquitously repeated regions of DNA in the human genome. Furthermore, these sequences appear to be highly conserved in eukaryotic genomes, but their function remains largely unknown. PMID- 2574140 TI - Oncogene expression in cholangiocarcinoma and in normal hepatic development. AB - The expression of the proteins encoded by the ras, myc, and erb B-2 oncogenes was examined in 63 paraffin-embedded human cholangiocarcinomas of Thai and English origin using immunohistochemistry. The observed distributions were compared with oncogene expression in a series of human hepatocellular carcinomas. In an attempt to relate expression of these three oncogenes to specific stages of normal tissue differentiation, tissue sections of normal fetal, infant, and adult human livers were also examined. Of 63 cholangiocarcinomas, 59 (95%) expressed p62 c-myc, 47 (75%) expressed p21 c-ras, and 46 (73%) expressed p190 c-erbB-2. The expression of c-myc and c-ras but not of c-erb B-2 correlated directly with tumor differentiation as judged by morphologic criteria. No difference was observed in oncogene expression between intrahepatic and extrahepatic cholangiocarcinomas. Twelve of 14 hepatocellular carcinomas (86%) stained positively for all three oncoproteins. During normal liver development, expression of c-myc and c-ras was shown to occur from 18 weeks' gestation until 5 years of age, but not thereafter. Expression of c-myc, c-ras, and c-erbB-2 oncogenes may be used as immunohistochemical markers to distinguish cholangiocarcinoma from nonneoplastic biliary tissues, and may provide useful information concerning the cell biology of tumor differentiation. PMID- 2574141 TI - A molecular genetic linkage map of mouse chromosome 4 including the localization of several proto-oncogenes. AB - We have constructed a 64-cM molecular genetic linkage map of mouse chromosome 4 using interspecific backcross animals derived from mating C57BL/6J and Mus spretus mice. Several proto-oncogenes and common sites of viral integration have been assigned regional locations on chromosome 4 including Mos, Lyn, Jun, Lmyc, Lck, Fgr, and Dsi-1. Additional loci mapped in this study to chromosome 4 were Tsha, Mup-1, Rrm2-ps1, Ifa, and Anf. A comparison of our mapping data with inbred strain mapping data did not show any evidence for inversions or deletions on chromosome 4. New regions of synteny were defined between mouse chromosome 4 and human chromosomes 1 and 8; a region of homology was found between mouse chromosome 4 and human chromosome 6. This linkage map will provide a framework for identifying homologous genes in mice and humans that may be involved in various disease processes. PMID- 2574142 TI - A genetic linkage map of 32 loci on human chromosome 10. AB - We have constructed a genetic linkage map of human chromosome 10 based on DNA probes that detect 47 restriction fragment length polymorphisms (RFLPs) at 32 different loci. Segregation data were collected on a set of multigenerational families provided by the Centre d'Etude du Polymorphisme Humain and maps were constructed using recently developed multipoint analysis techniques. The length of the sex-averaged map is 178 cM and the sex-specific map lengths are 131 cM in males and 255 cM in females. Recombination is significantly higher in female meioses. The mean distance between loci is 5.6 cM for the sex-averaged map. The genetic map spans the length of the chromosome as judged by physical localization of probes by in situ hybridization techniques and mapping of the probes on human hamster hybrid cell lines containing all or part of chromosome 10. The informativeness of two loci near the locus responsible for multiple endocrine neoplasia type 2A (MEN-2A) has been increased by isolation of cosmids that reveal additional RFLPs at these loci. PMID- 2574143 TI - Assignment of the gene for complete X-linked congenital stationary night blindness (CSNB1) to Xp11.3. AB - X-linked congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder characterized by a presumptive defect of neurotransmission between the photoreceptor and bipolar cells. Carriers are not clinically detectable. A new classification for CSNB includes a complete type, which lacks rod function by electroretinography and dark adaptometry, and an incomplete type, which shows some rod function on scotopic testing. The refraction in the complete CSNB patients ranges from mild to severe myopia; the incomplete ranges from moderate hyperopia to moderate myopia. To map the gene responsible for this disease, we studied eight multigeneration families, seven with complete CSNB (CSNB1) and one with incomplete CSNB, by linkage analysis using 17 polymorphic X-chromosome markers. We found tight genetic linkage between CSNB1 and an Xp11.3 DNA polymorphic site, DXS7, in seven families with CSNB1 (LOD 7.35 at theta = 0). No recombinations to CSNB1 were found with marker loci DXS7 and DXS14. The result with DXS14 may be due to the small number of scored meioses (10). No linkage could be shown with Xq loci PGK, DXYS1, DXS52, and DXS15. Pairwise linkage analysis maps the gene for CSNB1 at Xp11.3 and suggests that the CSNB1 locus is distal to another Xp11 marker, TIMP, and proximal to the OTC locus. Five-point analysis on the eight families supported the order DXS7-CSNB1-TIMP-DXS225-DXS14. The odds in favor of this order were 9863:1. Removal of the family with incomplete CSNB (F21) revealed two most favored orders, DXS7-CSNB1-TIMP-DXS255 DXS14 and CSNB1-DXS7-TIMP-DXS255-DXS14. Heterogeneity testing using the CSNB1-M27 beta and CSNB1-TIMP linkage data (DXS7 was not informative in F21) was not significant to support evidence of genetic heterogeneity (P = 0.155 and 0.160, respectively). PMID- 2574144 TI - Simultaneous genetic mapping of multiple human minisatellite sequences using DNA fingerprinting. AB - We have used several DNA probes which simultaneously recognize multiple loci to follow the segregation of a large number of minisatellite loci through two large reference pedigrees. The segregation data were analyzed for linkage to previously characterized marker loci using RFLP mapping data for these pedigrees from a previous study and from the Centre d'Etude du Polymorphisme Humain data bank. In this way we have mapped 31 separate minisatellite alleles of a total of 146 studied. The results of these analyses suggest that the distribution of minisatellites in the human genome is skewed toward telomeres and is highly clustered in character. A group of at least five separate minisatellites was found at 7 qter, and smaller clusters are present in several other regions. We detected a smaller than expected number of linkages, perhaps because of the clustering of minisatellite loci. The 7qter minisatellite cluster is in a region of excess male meiotic recombination, and in this respect is similar to minisatellite clusters at 16pter and in the X-Y pseudoautosomal region. PMID- 2574145 TI - Linkage map of mouse chromosome 17: localization of 27 new DNA markers. AB - Chromosome 17 of the laboratory variant of the house mouse (Mus musculus L.), MMU17, has been studied extensively, largely because of its involvement in the control of immune response and embryonic as well as male germ cell differentiation. A detailed linkage map of this chromosome is therefore a highly desired goal. As the first step toward achieving this goal, we have isolated, using a LINE 1 repetitive sequence as a probe, 52 anonymous DNA clones from MMU17. Twenty-seven repetitive sequence-free probes isolated from these clones displayed restriction fragment length variation among common inbred strains and could be mapped with the help of recombinant inbred strains, congenic strains, F2 segregants, or intra-t recombinants. Together with markers identified previously, the new markers can be used to construct a map of MMU17 that contains 125 DNA loci. The markers are distributed over a length of approximately 71 cM, which probably represents the entire length of MMU17. Most of the markers reside in the proximal portion of the chromosome, which contains the t and H-2 complexes; this chromosomal region is now fairly well mapped. The distal region of MMU17, on the other hand, is populated by only a few, rather imprecisely mapped markers. Molecular maps are available for most of the H-2 complex and for parts of the t complex. PMID- 2574146 TI - An analysis of variation in the long-range genomic organization of the human major histocompatibility complex class II region by pulsed-field gel electrophoresis. AB - The class II region of the human major histocompatibility complex in seven common HLA haplotypes has been analyzed using pulsed-field gel electrophoresis, restriction enzymes that cut genomic DNA infrequently, and Southern blotting. This analysis has revealed that there are differences in the amount of DNA present in the DQ and DR subregions dependent on the haplotype. The class II region of the DR3 haplotype spans approximately 750 kb and has the same amount of DNA as the class II region of the DR5 and DR6 haplotypes. However, the DR2 haplotype has approximately 30 kb more DNA within the DR subregion. The DR4 haplotype has an additional approximately 110 kb of DNA within the DQ or DR subregions compared to the DR3, DR5, and DR6 haplotypes. These haplotype-specific differences could have some bearing both on the analysis of disease susceptibility and on the ability of chromosomes possessing different HLA haplotypes to recombine within the DQ/DR subregions. PMID- 2574147 TI - The polymorphic marker DXS304 is within 5 centimorgans of the fragile X locus. AB - The fragile X syndrome, which is the most common cause of inherited mental retardation, poses important diagnostic problems for genetic counseling. The development of diagnostic strategies based on DNA analysis has been impaired by the lack of polymorphic markers very close to the disease locus. Here we report that the polymorphic probe U6.2 (locus DXS304) is much closer to the fragile X locus than all the previously reported markers. A recombination fraction of 0.02 between DXS304 and the fragile X locus was estimated by multipoint linkage analysis (confidence interval 0.002 to 0.05). Our data suggest that DXS304 is distal to the fragile X locus. This marker thus represents a major improvement for carrier detection and prenatal diagnosis in fragile X families. PMID- 2574148 TI - A new DNA marker (D4S90) is located terminally on the short arm of chromosome 4, close to the Huntington disease gene. AB - Genetic linkage studies have mapped Huntington's disease (HD) to the distal portion of the short arm of chromosome 4 (4p16.3), 4 cM distal to D4S10 (G8). To date, no definite flanking marker has been identified. A new DNA marker, D4S90 (D5); which maps to the distal region of 4p16.3, is described. The marker was used in a genetic linkage study in the CEPH reference families with seven other markers at 4p16. The study, together with knowledge of the physical map of the region, places D4S90 as the most distal marker, 6 cM from D4S10. A provisional linkage study with HD gave a maximum lod score of 2.14 at a theta of 0.00 and no evidence of linkage disequilibrium. As D4S90 appears to be located terminally, it should play an important role in the accurate mapping and cloning of the HD gene. PMID- 2574149 TI - A highly polymorphic locus cloned from the breakpoint of a chromosome 11p13 deletion associated with the WAGR syndrome. AB - Children with constitutional deletions of chromosome 11p13 suffer from aniridia, genitourinary malformations, and mental retardation and are predisposed to develop bilateral Wilms tumor (the WAGR syndrome). The critical region for these defects has been narrowed to a segment of band 11p13 between the catalase and the beta-follicle-stimulating hormone genes. In this report, we have cloned the endpoints from a WAGR patient whose large cytogenetic deletion, del(11)(p14.3::p13), does not include the catalase gene. The deletion was characterized using DNA polymorphisms and found to originate in the paternally derived chromosome 11. The distal endpoint was identified as a rearrangement of locus D11S21 in conventional Southern blots of the patient's genomic DNA, but was not detected in leukocyte DNA from either parent or in sperm DNA from the father. The proximal endpoint was isolated by cloning the junction fragment and was mapped in relation to other markers and breakpoints. It defines a new locus in 11p13-delta J, which is close to the Wilms tumor gene and the breakpoint cluster region (TCL2) of the frequent t(11;14)(p13;q11) translocation in acute T-cell leukemia. An unusual concentration of base pair substitutions was discovered at delta J, in which 9 of 44 restriction sites tested (greater than 20%) vary in the population. This property makes delta J one of the most polymorphic loci on chromosome 11 and may reflect an underlying instability that contributed to the original mutation. The breakpoint extends the genetic map of this region and provides a useful marker for linkage studies and the analysis of allelic segregation in tumor cells. PMID- 2574150 TI - Haplotypes in cystic fibrosis patients with or without pancreatic insufficiency from four European populations. AB - We examined the allele and haplotype frequencies of five polymorphic DNA markers in 355 European cystic fibrosis (CF) patients (from Belgium, the German Democratic Republic, Greece, and Italy) who were divided into two groups according to whether they were or not taking supplementary pancreatic enzymes. The level of linkage disequilibrium between each polymorphism and the CF mutation varied among the different populations; there was no significant association between KM.19 and CF in the Greek population. The distributions of alleles and haplotypes derived from the polymorphisms revealed by probes KM.19 and XV.2c were always different in patients with or without pancreatic insufficiency (PI) in all the populations studied. In particular, among 32 patients without PI, only 9 (or 28%) were homozygous for the KM.19-XV.2c = 2-1 haplotype (which was present in 73% of all the CF chromosomes in our sample) compared to 162 of 252 patients (or 64%) with PI. These findings are consistent with the hypothesis that pancreatic insufficiency or sufficiency may be determined by different mutations at the CF locus. PMID- 2574151 TI - Definition of mouse chromosome 1 and 3 gene linkage groups that are conserved on human chromosome 1: evidence that a conserved linkage group spans the centromere of human chromosome 1. AB - Comparative mapping between the human and the mouse genomes allows characterization of linkage groups that have been conserved over evolution. In this study, genes previously localized to adjacent regions of human chromosome 1 were mapped to discrete regions on distal mouse chromosomes 1 and 3 using an interspecific cross. Linkage analysis in mouse defined two groups in which the gene order appears to be the same as that in humans: 15 genes localized between human chromosome 1q21 and 1q32 were found to span 29.5 cM on distal mouse chromosome 1; 6 genes localized between human chromosome 1q21 and 1p22 spanned 15.6 cM on distal mouse chromosome 3. These data suggest that gene order within large chromosome segments may remain stable over long periods of evolution and that the position of the centromere may reflect a late event in the evolution of higher eukaryotic organisms. These studies provide a model for examination of specific evolutionary events. PMID- 2574152 TI - Characterization of eight VNTR loci by agarose gel electrophoresis. AB - Allelic frequencies and their confidence intervals were obtained for eight independent VNTR loci from a sample of more than 75 Utah Caucasians. Using high resolution agarose gel electrophoresis, we were able to resolve alleles at the D17S5 locus that differed by only one repeating unit; it was therefore possible to name the alleles according to the number of repeating units each contained. Two a priori probabilities were calculated for each VNTR locus separately and for all eight loci jointly: (i) the "power of exclusion" for an alleged father/mother/child trio and for an alleged parent/child duo, and (ii) the "probability of matching" when two unrelated individuals or two siblings are genotyped. PMID- 2574153 TI - CpG dinucleotides are mutation hot spots in phenylketonuria. AB - The coding region of the phenylalanine hydroxylase (PAH) gene contains 22 CpG dinucleotides, including five doublets in the seventh exon of the gene. We hypothesized that CpG doublets could represent mutation hot spots in PAH deficiencies and we carried out the systematic sequence analysis of exon 7 in 20 unrelated PAH-deficient kindreds of Mediterranean ancestry. This procedure resulted in the detection of two novel missense mutations whose location and nature (CG to CA and CG to TG) were consistent with the accidental deamination of a 5-methylcytosine in a CpG doublet (codon 261arg----gln and codon 252arg--- trp). Moreover, the codon 261 mutation was found to be associated with mutant restriction fragment length polymorphism (RFLP) haplotype 1, the most frequent mutant RFLP haplotype at the PAH locus in the studies reported thus far. However, since the mutation was detected in only 36% of haplotype 1 mutant alleles, it appears that this haplotype at the PAH locus is genotypically heterogeneous in Mediterranean countries. PMID- 2574154 TI - Allele frequencies of apolipoprotein A-I and A-II gene locus DNA polymorphisms in Boston-based whites. AB - Allele frequencies for four restriction fragment length polymorphisms of the apolipoprotein A-I gene locus and one restriction fragment length polymorphism of apolipoprotein A-II gene locus were determined in more than 100 North American whites and are reported herein. PMID- 2574155 TI - Restriction fragment length polymorphism of human salivary alpha-amylase in a Japanese population. AB - Restriction fragment length polymorphism of human salivary alpha-amylase after cleavage with restriction endonucleases PstI and BamHI was studied in a population from eastern Japan. Among 40 unrelated individuals, the frequencies of the 5.7- and 6.5-kilobasepair fragment alleles were 0.487 and 0.513, respectively. PMID- 2574156 TI - Polymorphism of T-cell receptor genes among laboratory and wild mice: diverse origins of laboratory mice. AB - Southern blots of genomic DNA from 23 strains of laboratory mice and 19 individual wild mice were examined for restriction fragment length polymorphisms in their loci encoding the T-cell receptors (Tcr): the constant regions of the alpha, beta, and gamma chains (C alpha, C beta, and C gamma) and a variable region family of the beta chain (V beta 8). Only a few polymorphisms were observed for each locus in the laboratory mice after using three restriction enzymes, Bam HI, Eco RI, and Hind III. All the laboratory mice examined fall into one of two types for the C alpha, C beta, and V beta 8 loci and one of three types for the C gamma. These types are found in some of the wild mice studied, indicating that they were already present in the founder mice of laboratory mouse strains. In contrast, the Tcr genes are highly polymorphic among wild mice. Analysis of the polymorphisms in these loci suggests that laboratory mice have inherited their genes not only from Mus musculus domesticus, but also from other subspecies, and much more than previously believed from Asian subspecies. PMID- 2574157 TI - Quantitative variation of C4 variant proteins associated with many MHC haplotypes. AB - C4 protein variants were analyzed in 64 individuals, of which 51 were either homozygous or heterozygous for an extended major histocompatibility complex (MHC) haplotype (a fixed combination of MHC alleles). The relative amount of each C4 variant was measured by densitometric scanning of stained immunofixed electrophoretic patterns of neuraminidase- and carboxypeptidase-treated samples. The relative concentrations of C4 variants on any haplotype were stable and inherited in families. In five of the eight extended haplotypes investigated, the amount of one of the C4 variants relative to others in the same pattern was increased: [HLA-B8, SC01, DR3] and [HLA-B7, SC31, DR2] produced an approximately doubled amount of C4B1; [HLA-B18, S042, DR2] an increased amount of C4B2; and [HLA-B44, SC30, DR4] a double amount of C4A3. The extended haplotype [HLA-Bw57, SC61, DR7] gave rise to two to three times as much C4B1 as C4A6. In the extended haplotypes [HLA-B44, FC31, DR7] and [HLA-Bw62, SC33, DR4], the results did not clearly indicate differences in expression of the C4 isotypes. DNA analysis possibly supported an actual gene duplication only for the haplotype [HLA-B7, SC31, DR2]. The results suggest that, in addition to variation in the number of structural genes, other MHC-linked mechanisms may be involved in the regulation of the relative amounts of C4A or C4B protein specified by any haplotype. PMID- 2574158 TI - RFLP analysis of the HLA-, ChLA-, and RhLA-DQ alpha chain gene regions: conservation of restriction sites during evolution. AB - Genomic DNA samples, derived from a panel of 60 chimpanzees and 45 rhesus monkeys, were digested with the restriction enzymes Taq I and Bgl II and hybridized with an HLA-DQ alpha chain cDNA probe. The results were compared with the data available on a human reference panel. Use of the restriction enzyme Taq I and the DQ alpha chain probe allows the detection of five HLA-DQA1 and two HLA DQA2 gene-associated fragments within the human population. For the ChLA and RhLA systems, 3 and 7 different DQA1-associated restriction patterns were detected, respectively, while for the chimpanzee a nonpolymorphic DQA2 (DX alpha) gene associated fragment was also observed. The equivalent of the HLA- and ChLA-DQA2 genes appears to be absent in the rhesus monkey. The ChLA-DQA1 and -DQA2 gene associated RFLP patterns are identical in man and chimpanzee, whereas such restriction site conservation is not seen in the rhesus monkey. The conclusion drawn is that the genetic organization of the HLA-DQA and ChLA-DQA gene regions, and possibly some of their allelic variabilities, already existed before man and chimpanzee separated in evolution. Moreover, the particular duplication which led to the generation of the HLA- and ChLA-DQA2 genes must have happened before speciation of members belonging to the superfamily Hominoidea (man, chimpanzee, etc), but probably after the separation of superfamily Cercopitecoidea (rhesus monkeys, baboons, etc.) from Hominoidea. PMID- 2574160 TI - Restriction fragment analysis of non-deleted complement C4 null genes suggests point mutations in C4A null alleles, but gene conversions in C4B null alleles. PMID- 2574159 TI - Mouse Vk gene classification by nucleic acid sequence similarity. AB - Analyses of immunoglobulin (Ig) variable (V) region gene usage in the immune response, estimates of V gene germline complexity, and other nucleic acid hybridization-based studies depend on the extent to which such genes are related (i.e., sequence similarity) and their organization in gene families. While mouse Igh heavy chain V region (VH) gene families are relatively well-established, a corresponding systematic classification of Igk light chain V region (Vk) genes has not been reported. The present analysis, in the course of which we reviewed the known extent of the Vk germline gene repertoire and Vk gene usage in a variety of responses to foreign and self antigens, provides a classification of mouse Vk genes in gene families composed of members with greater than 80% overall nucleic acid sequence similarity. This classification differed in several aspects from that of VH genes: only some Vk gene families were as clearly separated (by greater than 25% sequence dissimilarity) as typical VH gene families; most Vk gene families were closely related and, in several instances, members from different families were very similar (greater than 80%) over large sequence portions; frequently, classification by nucleic acid sequence similarity diverged from existing classifications based on amino-terminal protein sequence similarity. Our data have implications for Vk gene analyses by nucleic acid hybridization and describe potentially important differences in sequence organization between VH and Vk genes. PMID- 2574161 TI - The effect of beta-adrenoceptor antagonists alone and in combination with a GABA elevating agent on isoniazid-induced convulsions in rats. AB - A delay in the onset of isoniazid-induced convulsions was found in rats pretreated with the beta 2-adrenoceptor blocker, butoxamine and the nonspecific beta-blocker, propranolol. In these animals the convulsive responses were inhibited in a dose dependent manner. These compounds were found to be effective even after the induction of convulsions. The beta 1-blocker, acebutolol was able to protect rats only when injected prior to the challenge. The anticonvulsant effect of acebutolol and propranolol but not that of butoxamine was found to be enhanced in animals pretreated with a gamma-aminobutyric acid (GABA) elevating agent, aminooxyacetic acid (AOAA). The findings indicate that the GABA-mediated anticonvulsant action of AOAA seems to be additive with that resulting from beta 1 but not beta 2-blockade. PMID- 2574162 TI - Glutamate receptor-linked changes in membrane potential and intracellular Ca2+ in primary rat astrocytes. AB - Kainate-, quisqualate- and glutamate-induced depolarization and mobilization of intracellular Ca2+ was determined in primary cultured astrocytes using the fluorescent probes DiBa-C4-(3) and fura-2, respectively. All three receptor agonists depolarized the cells in a Na+-dependent manner and increased the intracellular Ca2+ concentration. The glutamate- and quisqualate-induced increase in cytosolic Ca2+ was only partially inhibited by removal of extracellular Ca2+, whereas the response to kainate was totally dependent on extracellular Ca2+. The mechanisms for depolarization and increases in cytosolic Ca2+ appeared to be independent of each other, as extracellular Ca2+ removal or intracellular Ca2+ buffering with entrapped BAPTA did not affect the depolarization. Removal of extracellular Na+ did not affect the agonist-induced increase in Ca2+. If quisqualate was added after kainate, the cells were hyperpolarized in a Ca2+- and K+-dependent manner. This could be due to effects on a Ca2+-dependent K+ channel, the effects of which are normally hidden by the greater effect on Na+ channels as a response to quisqualate. PMID- 2574163 TI - Anatomy, physiology, and elementary pharmacology of the autonomic nervous system. PMID- 2574164 TI - Electrophysiology of ganglionic transmission in the sympathetic nervous system. AB - The sympathetic nervous system contributes to the regulation and control of a great number of body functions. A considerable fraction of preganglionic fibers are constantly discharging nerve impulses, and this tonic activity is responsible for a number of sustained bodily conditions. These tonic sympathetic discharges are of central origin and may be decreased by inhibition or augmented by excitation of the central neural mechanisms in control of the relevant preganglionic neurons. Certain other sympathetic paths become active only when special conditions lead to excitation of their central connections. The effect of the activity of preganglionic fibers on the different target organs, however, does not depend entirely on central regulatory influences. The sympathetic ganglia play a significant role processing and integrating the information arriving from the central nervous system and controlling the output to the target organs. In this context, the different potentials described above constitute the basis for the integrative process to occur. We now have substantial information about the basic biophysical events associated with different electrical events in the sympathetic ganglia. Very little is known, however, about how they operate in an integrative manner to control specific functions. The control of sympathetic responses during surgical stimulation is an important goal of general anesthesia. General anesthetics may operate to produce this effect at both central and peripheral levels. The sympathetic ganglion as a peripheral synapse, with basic integrative properties similar to the complex central nervous system, is a model still not sufficiently exploited to understand mechanisms by which general anesthetics control sympathetic response. The relevance of the findings described above in a variety of clinical situations, such as stress, hypertension, exercise, and anesthesia, remains to be studied. PMID- 2574165 TI - Novel abnormality in subpopulations of circulating lymphocytes. T gamma delta and CD2-, 3+, 4-, 8- lymphocytes in histoplasmosis-associated immunodeficiency. AB - A patient, who had developed anergy after disseminated histoplasmosis and who had gone on to develop a cardiomyopathy, demonstrated an unusually large proportion of T lymphocytes bearing the gamma and delta chains of the T cell receptor (TCR gamma/delta). These gamma delta + cells composed over half of the circulating lymphocytes and were clearly divisible into two subgroups based on the level of expression of the gamma and delta chains and their ability to bind one of the monoclonal antibodies reactive with the TCR-delta chain. In addition, the patient showed an abnormally high proportion of circulating lymphocytes having the CD2-, 3+, 4-, 8- phenotype which has been only recently described. The pattern of lymphocyte subpopulations changed over the 9 years that the patient was followed since his original infection and appears to characterize a novel abnormality. PMID- 2574167 TI - Pain management in the chemically dependent patient. AB - The individual who suffers from chemical dependency has unique physiological and psychological conditions that make the management of acute and chronic disabling conditions challenging, frustrating or stressful, depending upon the experience of his primary attending physician. Several general principles are helpful in this situation. Special conditions, such as tolerance to opiate analgesics, and methadone maintenance, require special attention. The desire to treat the person who has an admitted or suspected history of chemical dependence presents conflicting interests for the attending physician. While there is the desire to provide the best possible care for any patient, this must be balanced against contributing to the patient's primary problem with drugs, and perhaps worse yet, the fear of being used by the patient to provide him with drugs to support his drug habit. The fear of dealing with a patient who is "running a scam" to obtain prescription drugs, or the anxiety of having to deal with an overly zealous DEA agent, further complicates the physician's role in the care of these parties. PMID- 2574166 TI - Increased delayed-type hypersensitivity reaction in rats neuromanipulated with capsaicin. AB - We studied the neuroimmunomodulatory effect of capsaicin on the development of delayed-type hypersensitivity (DTH) reaction and antibody formation after reduction of neuropeptides in the peripheral sensoric nervous system. Rats were sensitized with picryl chloride on their shaved abdomen or by subcutaneous injections with picrylsulfonic acid (PSA). Manipulation of the content of neuropeptides in the sensory nerve system with capsaicin was performed 1 week before or after sensitization. An increase of the DTH reaction assessed as increased ear thickness after challenge was seen especially when the rats were given capsaicin after sensitization. The formation of specific antibodies was not affected, although the level of total IgG was decreased in PSA-sensitized rats treated with capsaicin after sensitization. The results demonstrated that the DTH reaction in rat was slightly but significantly affected by the abolishment of neuropeptides in sensoric nerve endings with capsaicin. Even if the direct effect of capsaicin on the immune system still has to be elucidated, these results indicate that neuropeptides in sensory nerves are involved in the pathogenesis of DTH. PMID- 2574168 TI - Acute effects of beta-adrenergic agonists on porcine adipocyte metabolism in vitro. AB - Backfat was obtained at slaughter from market weight hogs to study the acute effects of clenbuterol (CB), ractopamine (RAC) or epinephrine (EPI), in the presence and absence of theophylline (THEO) or adenosine deaminase (ADA), on rates of lipolysis and fatty acid synthesis in vitro. Only EPI increased lipolytic rate in the absence of THEO or ADA. In the presence of THEO or ADA, RAC and CB were lipolytic, although CB had a lower maximal response. With THEO present, RAC and EPI increased lipolysis with a similar potency and responsiveness. Lipolytic responses from all agonists were prevented by propranolol. Insulin stimulated glucose incorporation into fatty acids 50 to 100%; stimulated rates were not influenced by any agonist, either alone or in the presence of ADA. When THEO was present, EPI and RAC inhibited fatty acid synthesis approximately 50%. Clenbuterol was not inhibitory under any conditions. Results indicate that, under appropriate conditions, beta-adrenergic agents increase lipolysis and decrease lipogenesis in porcine adipocytes. Combined evidence suggests that lipolysis is more sensitive to beta-adrenergic stimulation than is insulin-stimulated lipogenesis. Finally, RAC and CB possess only partial agonist activity relative to EPI, CB being least active. PMID- 2574169 TI - Determination of the affinity of ractopamine and clenbuterol for the beta adrenoceptor of the porcine adipocyte. AB - Dissociation constants (Kd) of ractopamine and clenbuterol for the swine adipocyte beta-adrenergic receptor were estimated from competition studies with epinephrine for the stimulation of lipolysis. Both compounds competitively inhibited epinephrine-stimulated lipolysis in the absence of adenosine deaminase. Three methods for estimating Kd values were used and similar estimates were obtained with each method. Ractopamine and clenbuterol showed greater affinity for the beta-receptor than did epinephrine and had similar Kd values of 1 to 2 x 10(-7) M. The low capacity of ractopamine and clenbuterol to stimulate lipolysis in vitro does not result from poor coupling to the beta-receptor. Ractopamine and clenbuterol may be considered partial agonists, possessing high affinity for the beta-adrenoceptor but exhibiting a relative ineffectiveness for adenylate cyclase activation. PMID- 2574170 TI - Changing adrenergic sensitivity of the caruncular arterial vasculature supplying the bovine placentome. AB - With the advancement of gestation, blood flow increases preferentially to the caruncular bed of the gravid uterus in association with a decreasing sensitivity of the uterus to the vasoconstrictive effects of circulating catecholamines. This study directly compared the sensitivity of the caruncular artery (CA) of the isolated bovine placentome to phenylephrine (PE), a specific alpha 1-adrenergic receptor (AR) agonist, with that to norepinephrine (NE) and epinephrine (E), both of which are alpha 1-, alpha 2-, and beta-AR agonists, at two stages of gestation (140 to 170 d, mid-pregnant; 210 to 270 d, late pregnant). The CA of each placentome was perfused with oxygenated Krebs Ringer solution into which PE, NE or E were administered; increases in intra-arterial pressure were recorded. Further, NE content and numbers of alpha 1- and alpha 2-AR in the CA, intercaruncular arteries (ICA) and uterine arteries (UA) were quantitated. The CA from mid-pregnant cows exhibited greater (P less than .05) contractile responses to NE and E than did the CA from late pregnant cows, whereas responsiveness to PE remained constant. No difference in NE content, alpha 1-AR or alpha 2-AR numbers were observed in the UA, ICA or CA between mid-pregnant or late pregnant cows. Alpha 1-AR numbers were similar in CA, ICA and UA. However, CA contained threefold greater alpha 2-AR numbers than either the ICA or UA (50.2 +/- 6.1 vs 14.6 +/- 1.6 and 14.8 +/- 2.4 fmol/mg protein, respectively; P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574171 TI - Intracranial suppuration. PMID- 2574172 TI - Interhemispheric empyema. An unusual form of subdural empyema. AB - A 16 year old male was admitted with a clinical picture suggesting an intracranial pyogenic infection. He also has focal convulsions and left abducens palsy. CT scan showed a subdural empyema with interhemispheric extension. Since the patient was improving clinically, neurosurgical intervention was deferred. Spontaneous interhemispheric empyema is an uncommon condition. In our case conservative management was curative in what is considered a neurosurgical emergency. PMID- 2574173 TI - Beta blockers in depression. PMID- 2574174 TI - A cryptic fimbrial gene in Serratia marcescens. AB - The gene coding for the mannose-sensitive hemagglutinating fimbriae in Serratia marcescens US5 was cloned into Escherichia coli K4 with a cosmid vector system. One of the transformants, US5-1, expressed two morphologically distinct fimbriae, one that was 5-nm wide and one that was 3-nm wide. The latter fimbria was morphologically and serologically indistinguishable from that of strain US5. Genetic analysis of transformant US5-1 showed that the gene responsible for the 5 nm-wide fimbriae was located more than 10 kilobases away from the gene responsible for the 3-nm-wide fimbriae. The molecular sizes of the subunits of these two fimbriae, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were 19 kilodaltons for the 3-nm-wide fimbriae and 20 kilodaltons for the 5-nm-wide fimbriae. Serologically, the 5-nm-wide fimbriae did not cross-react with monoclonal or polyclonal antibodies raised against the mannose-sensitive hemagglutinating fimbriae of strain US5. Strain EL101, which expressed only the 5-nm-wide fimbriae, did not agglutinate chicken or human erythrocytes. These experimental results suggest that the gene for the 5-nm-wide fimbriae is cryptic in strain US5 and is expressed in E. coli K4 only after it is moved by transformation. PMID- 2574175 TI - Beta-adrenergic and somatostatin receptors regulate Na-H exchange independent of cAMP. AB - Activation of beta-adrenergic and somatostatin receptors increases and attenuates, respectively, cAMP. We have determined, however, that in enteric endocrine cells beta-adrenergic and somatostatin receptors also regulate Na-H exchange activity, independent of their effects on cAMP. In cells loaded with a pH-sensitive dye, epinephrine, acting at a beta 2-adrenergic receptor induced an alkalinization while somatostatin caused an acidification of intracellular pH (pHi). These pHi changes were dependent on extracellular Na+ and inhibited by amiloride. Forskolin, dibutyryl-cAMP and 8-bromo-cAMP, however, had no effect on pHi. Cholera toxin, while decreasing the EC50 for epinephrine-stimulated increases in cAMP, had no effect on epinephrine-induced alkalinization, suggesting receptor coupling to Na-H exchange was not mediated by a cholera toxin sensitive stimulatory GTP-binding protein (Gs). Additionally, epinephrine stimulated Na-H exchange in cyc- variants of S49 lymphoma cells, which lack a fundamental Gs. In the presence of pertussis toxin, somatostatin attenuation of cAMP was completely reversed; however, somatostatin inhibition of Na-H exchange was not affected. We suggest that beta-adrenergic and somatostatin receptors regulate Na-H exchange independent of changes in cAMP and possibly independent of GTP-binding proteins previously described as being coupled to these receptors. PMID- 2574176 TI - Sequence requirements for cytochrome P-450IIB1 catalytic activity. Alteration of the stereospecificity and regioselectivity of steroid hydroxylation by a simultaneous change of two hydrophobic amino acid residues to phenylalanine. AB - The phenobarbital-inducible P-450 forms IIB1 and IIB2 are identical in sequence except for 14 amino acid differences within the carboxyl-terminal half of the molecule. IIB1 has about a 5-10-fold higher turnover number for most monooxygenase substrates examined although the substrate specificities of both enzymes are virtually identical. Both P-450s oxygenate testosterone to yield the 16 alpha-hydroxy, 16 beta-hydroxy, 17-keto, and 16 beta-hydroxy, 17-keto metabolites as major products. A variant IIB2 cDNA, isolated from an uninduced rat liver lambda gt11 library, and when expressed in Hep G2 cells using a vaccinia virus vector, was found to code for a protein that produced the 16 alpha hydroxy and 17-keto metabolites of testosterone but no 16 beta-hydroxylated products. Although the published sequences of IIB1 and IIB2 are identical within the N-terminal halves of the proteins, sequence analysis of the variant cDNA revealed two amino acid substitutions in this region; Leu58----Phe and I1e114--- Phe. When these two amino acid changes were incorporated into IIB1, via construction of a chimeric cDNA, the resultant expressed enzyme did not catalyze the 16 beta-hydroxylation of testosterone or androstenedione. Formation of the 16 alpha-hydroxy and 17-keto metabolites, however, was only slightly reduced compared with the parent IIB1. A IIB1 protein that possessed only the I1e114--- Phe replacement catalyzed the production of all four testosterone metabolites with only slightly different product ratios compared with the parent enzyme. The substrate specificity of a IIB1 variant containing only the Leu58----Phe replacement could not be determined, since that protein did not accumulate in cells infected with the corresponding recombinant vaccinia virus. These data suggest that two distinct amino acid residues located within the amino-terminal fourth of IIB1 and IIB2 can affect substrate orientation at the active site. PMID- 2574179 TI - Altered responses of regenerating hepatocytes to norepinephrine and transforming growth factor type beta. AB - Norepinephrine (NE), acting through the alpha 1-adrenergic receptor, modules the response of rat hepatocytes in primary culture to transforming growth factor type beta 1 (TGF beta) by increasing the amount of TGF beta required for a given degree of inhibition of epidermal growth factor (EGF)-induced DNA synthesis (Houck et al., J. Cell. Physiol. 135:551-555, 1988). This effect was also found in hepatocytes isolated from regenerating livers but was greatly magnified in cells isolated between 12 and 18 hr after two-thirds partial hepatectomy (PHX). During this period of enhanced sensitivity, NE was equally potent in terms of dose but more efficacious in the regenerating hepatocytes. As it did in control hepatocytes (Cruise et al., Science 227:749-751, 1985), the alpha 1-adrenergic receptor mediated the activity of NE in regenerating hepatocytes. Vasopressin (VP) and angiotensin-II (AG) also antagonized the effect of TGF beta and showed increased activity in regenerating hepatocytes but at only 50% or less of the maximal effect reached by NE. Regenerating hepatocytes isolated 24-72 hr after PHX exhibited decreased sensitivity to inhibition by TGF beta, with a nadir in 48 hr-regenerating cells. These findings suggest that NE may be involved in triggering the early phase of DNA synthesis during liver regeneration, with the subsequent acquisition of innate resistance to TGF beta responsible for continued proliferation at a time when TGF beta mRNA is known to be increasing in the liver (Braun et al., Proc. Natl. Acad. Sci. USA 85:1539-1543, 1988). EGF induced increased DNA and protein synthesis in cultures of control hepatocytes; TGF beta inhibited the EGF-induced DNA synthesis but had no effect on protein synthesis. This may be relevant to the latter stages of liver regeneration, when high levels of TGF beta mRNA are detected in liver and cellular hypertrophy predominates over hyperplasia. PMID- 2574177 TI - Identification of microtubule-associated proteins in the centrosome, spindle, and kinetochore of the early Drosophila embryo. AB - We have developed affinity chromatography methods for the isolation of microtubule-associated proteins (MAPs) from soluble cytoplasmic extracts and have used them to analyze the cytoskeleton of the early Drosophila embryo. More than 50 Drosophila embryo proteins bind to microtubule affinity columns. To begin to characterize these proteins, we have generated individual mouse polyclonal antibodies that specifically recognize 24 of them. As judged by immunofluorescence, some of the antigens localize to the mitotic spindle in the early Drosophila embryo, while others are present in centrosomes, kinetochores, subsets of microtubules, or a combination of these structures. Since 20 of the 24 antibodies stain microtubule structures, it is likely that most of the proteins that bind to our columns are associated with microtubules in vivo. Very few MAPS seem to be identically localized in the cell, indicating that the microtubule cytoskeleton is remarkably complex. PMID- 2574178 TI - Cytoskeletal distribution and function during the maturation and enucleation of mammalian erythroblasts. AB - We have used murine splenic erythrolasts infected with the anemia-inducing strain of Friend virus (FVA cells), as an in vitro model to study cytoskeletal elements during erythroid maturation and enucleation. FVA cells are capable of enucleating in suspension culture in vitro, indicating that associations with an extracellular matrix or accessory cells are not required for enucleation to occur. The morphology of FVA cells undergoing enucleation is nearly identical to erythroblasts enucleating in vivo. The nucleus is segregated to one side of the cell and then appears to be pinched off resulting in an extruded nucleus and reticulocyte. The extruded nucleus is surrounded by an intact plasma membrane and has little cytoplasm associated with it. Newly formed reticulocytes have an irregular shape, are vacuolated and contain all cytoplasmic organelles. The spatial distribution of several cytoskeletal proteins was examined during the maturation process. Spectrin was found associated with the plasma membrane of FVA cells at all stages of maturation but was segregated entirely to the incipient reticulocyte during enucleation. Microtubules formed cages around nuclei in immature FVA cells and were found primarily in the incipient reticulocyte in cells undergoing enucleation. Reticulocytes occasionally contained microtubules, but a generalized diffuse distribution of tubulin was more common. Vimentin could not be detected at any time in FVA cell maturation. Filamentous actin (F-actin) had a patchy distribution at the cell surface in the most immature erythroblasts, but F-actin bundles could be detected as the cells matured. F-actin was found concentrated between the extruding nucleus and incipient reticulocyte in enucleating erythroblasts. Newly formed reticulocytes exhibited punctate actin fluorescence whereas extruded nuclei lacked F-actin. Addition of colchicine, vinblastine, or taxol to cultures of FVA cells did not affect enucleation. In contrast, cytochalasin D caused a complete inhibition of enucleation that could be reversed by washing out the cytochalasin D. These results demonstrate that F actin plays a role in enucleation while the complete absence of microtubules or excessive numbers of polymerized microtubules do not affect enucleation. PMID- 2574180 TI - Effects of aging on the immune system. AB - Most cell-mediated and humoral immune responses decline with advancing age. Both the T- and B-cell compartments show deficiencies in activation, transit through the cell cycle, and subsequent differentiation. The T-cell compartment, notably the CD4 subset, which includes helper cells, is most affected by thymic involution. The mucosal immune system is relatively unaffected. PMID- 2574181 TI - Early differentiation of senile dementias. AB - Neurologic causes of dementia include cortical and subcortical pathology, as well as intracranial space-occupying lesions. The elderly are particularly prone to metabolic and toxic encephalopathies with associated delirium, dementia, or both. Many of these disorders are potentially reversible, but appropriate management requires comprehensive assessment. PMID- 2574182 TI - Quantitation of selective dopaminergic drugs in plasma by gas chromatography-mass spectrometry following solid-phase extraction. PMID- 2574183 TI - Isolation of HIV using T-lymphocyte 'panning': methodological aspects. AB - A technique for isolation of HIV using selective cultures of T4 cells obtained from peripheral blood by immunochemical separation was developed and optimized. Using this method infectious virus could be isolated in single isolation attempts from 89% of 35 HIV-infected patients in different stages of immunodeficiency. This isolation frequency was virtually independent of the stage of the disease, in contrast to the results obtained by the conventional isolation technique based on peripheral mononuclear cells (PMC). It is concluded that isolation of HIV from selected T4 cells is superior to other methods when isolation is attempted from healthy HIV-infected individuals. PMID- 2574184 TI - Peroxidase-labeled primary antibody method for detection of pestivirus contamination in cell cultures. AB - Contaminating bovine viral diarrhea (BVD) virus in cell cultures and in fetal bovine serum (FBS) is a well recognized problem. This study describes a direct peroxidase (DP) labeled primary antibody method for detection of pestivirus antigens in cell culture that is simple and reliable. Using this method, most bovine and porcine cell cultures, a cat lung, four mosquito and two monkey cell cultures were found contaminated with BVD virus. The rodent and human cell cultures tested were negative by this method for BVD virus. PMID- 2574185 TI - Relationship among selected Leptospira interrogans serogroups as determined by nucleic acid hybridization. AB - Leptospiral DNAs from a variety of Leptospira interrogans serogroups of veterinary significance, as well as a nonpathogenic leptospira, were compared by Southern blot hybridization of EcoRI-digested genomic DNA. The serogroups examined could be assigned to one of three groups on the basis of the degree of cross-hybridization between genomic DNAs. Only a few restriction fragments hybridized between the three groups, and most of these were shown to contain ribosomal DNA. The restriction fragment length polymorphism observed among the intergroup hybridizations allowed differentiation among serogroups and, in some cases, serovars. Under the hybridization conditions used, no hybridization was observed between leptospiral DNA and Leptonema, Escherichia coli, or porcine DNA. PMID- 2574186 TI - DNA polymorphism in Mycobacterium paratuberculosis, "wood pigeon mycobacteria," and related mycobacteria analyzed by field inversion gel electrophoresis. AB - Mycobacterium paratuberculosis strains, mycobacteria from patients suffering from Crohn's disease, "wood pigeon mycobacteria," and representatives of Mycobacterium avium-Mycobacterium intracellulare were compared by restriction endonuclease DraI digestion and field inversion gel electrophoresis. Characteristic profiles were seen for M. paratuberculosis, including isolates from patients suffering from Crohn's disease, for wood pigeon mycobacteria, and for M. avium-M. intracellulare serotypes 2, 16, 18, and 19. Two M. paratuberculosis strains used for vaccine production (St 18 and 316 F) presented patterns different from those of the other M. paratuberculosis strains. Strains St 18 yielded a pattern identical to that of the M. avium type strain serotype 2, whereas 316 F gave a unique pattern. The method developed in this study represents a useful taxonomic tool for the identification and classification of mycobacteria. PMID- 2574187 TI - Defective dopamine-1 receptor adenylate cyclase coupling in the proximal convoluted tubule from the spontaneously hypertensive rat. AB - The natriuretic effect of DA-1 agonists is less in the spontaneously hypertensive rat (SHR) than its normotensive control, the Wistar-Kyoto rat (WKY). To determine a mechanism of the decreased effect of DA-1 agonists on sodium transport, DA-1 receptors in renal proximal convoluted tubule (PCT) were studied by radioligand binding and by adenylate cyclase (AC) determinations. Specific binding of 125I SCH 23982 (defined by 10 microM SCH 23390, a DA-1 antagonist) was concentration dependent, saturable, and stereoselective. The dissociation constant, maximum receptor density, and DA-1 antagonist inhibition constant were similar in SHR and WKY. The apparent molecular weight of the DA-1 receptor determined by the photoaffinity D1 probe 125I-MAB was also similar in WKY and SHR. However, DA-1 agonists competed more effectively for specific 125I-SCH 23982 binding sites in WKY than in SHR. Basal as well as forskolin, parathyroid hormone, GTP and Gpp(NH)p-stimulated-AC activities were similar. In contrast DA-1 agonists (fenoldopam, SKF 38393, SND 911C12) stimulated AC activity to a lesser extent in SHR. GTP and Gpp(NH)p enhanced the ability of DA-1 agonists to stimulate AC activity in WKY but not in SHR. These data suggest a defect in the DA-1 receptor second messenger coupling mechanism in the PCT of the SHR. PMID- 2574188 TI - Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, human immunodeficiency virus-seropositive patients. Independence of CD4+ cell numbers and clinical staging. AB - We have tested the T helper cell (TH) potential of asymptomatic, HIV seropositive (HIV+) patients, using an in vitro assay for IL-2 production. Peripheral blood leukocytes (PBL) from 74 HIV+ patients and 70 HIV- control donors were tested for TH function when stimulated with influenza A virus (FLU), tetanus toxoid (TET), HLA alloantigens (ALLO), or PHA. Of the HIV+ patients, four different response patterns were observed: (a) patients who responded to all four stimuli (16%); (b) patients who were selectively unresponsive to FLU and TET, but responded to ALLO and PHA (54%); (c) patients who were unresponsive to FLU, TET, or ALLO, but responsive to PHA (16%); and (d) patients who failed to respond to any of these stimuli (14%). Our results indicate a time-dependent progression from a stage responsive to all four stimuli to a stage unresponsive to any of the stimuli tested, progressing in the order outlined above. The earliest TH defect is the loss of responses to FLU and TET, indicating a selective defect in CD4+ MHC self restricted TH function. The later loss of ALLO and PHA IL-2 responses suggests more severe TH dysfunction involving both CD4+ and CD8+ T cells. None of these patterns of TH unresponsiveness in asymptomatic HIV+ individuals were correlated with CD4+ cell numbers nor with Walter Reed staging criteria. This study indicates that the in vitro TH assay used can detect multiple stages of immune dysregulation early in the course of HIV infection and raises the possibility that staging of HIV+ patients should include in vitro TH functional analyses of the type described here. PMID- 2574189 TI - Implications of altered drug disposition in the elderly: studies of benzodiazepines. PMID- 2574191 TI - Successful clonazepam treatment of neuroleptic-induced akathisia in older adolescents and young adults: a double-blind, placebo-controlled study. AB - In a double-blind, placebo-controlled trial of clonazepam in the treatment of neuroleptic-induced akathisia in older adolescents, clonazepam was significantly more effective at reducing akathisia scores at the end of the first treatment week than placebo (p less than 0.0001). Clonazepam may be a safe and effective treatment for neuroleptic-induced akathisia in this age group. PMID- 2574190 TI - Nizatidine suppression of basal gastric acid output: a comparison of two intravenous dosage regimens. AB - To study the pharmacokinetics and pharmacodynamics of two intravenous nizatidine dosing regimens, serial plasma concentrations and continuous intragastric pH were monitored simultaneously in 10 subjects with a documented history of duodenal or gastric ulcers. A 24-hour gastric pH profile was characterized for a 300 mg daily dose of nizatidine randomly administered both as 100 mg every 8 hours and 150 mg every 12 hours. No significant differences were observed in the mean pharmacokinetic parameters between the two dosing regimens. Pharmacodynamic parameters for the 100 mg every 8 hours versus the 150 mg every 12 hours regimen were not significantly different except for percent of time during the 24-hour study period that the pH was maintained greater than 4 (43.6 +/- 20.7 versus 34.7 +/- 18.3, P less than .05). A significant relationship was demonstrated for both regimens (P less than .05) between the percent time pH greater than 4 and area under the plasma curve for the 24 hour study period. The lack of a significant difference in nizatidine pharmacokinetics between the two dosage regimens suggests a pharmacodynamic cause for the greater cumulative pH effect of the every 8 hour regimen. PMID- 2574192 TI - Effects of anticholinergic agents on patients with tardive dyskinesia and concomitant drug-induced parkinsonism. AB - Twenty-five percent of 80 consecutive patients who met research criteria for persistent tardive dyskinesia (TD) were found to have an energy peak in the parkinsonian tremor band (3-6 Hz) of the frequency spectrum of their machine measured resting hand movements in addition to the abnormalities consistent with TD (increased energy in the 0.5-3 Hz frequency spectrum). Twelve of these patients were studied again in double-blind fashion 2 hours after receiving a placebo and again 2 hours after a single 4 mg dose of trihexyphenidyl hydrochloride (HCl). Compared with the placebo condition, the trihexyphenidyl HCl markedly diminished the measured energy in the 4 Hz band and had no effect or slightly decreased the energy at all other points on the frequency spectrum. Simultaneous Abnormal Involuntary Movement Scale ratings revealed no change in the dyskinetic movements between the conditions; there was a significant subjective improvement reported by the patients following the trihexyphenidyl HCl administration. These observations indicate that electromechanical devices identify a subpopulation of TD patients who may acutely benefit from anticholinergic treatment. PMID- 2574193 TI - A clinical scale to assess benzodiazepine withdrawal. AB - The objective, sensitive, and reliable quantitation of withdrawal symptoms is essential to assess physical dependence on drugs. Data collected from 23 patients abusing high doses of benzodiazepines (mean diazepam dose equivalents, 150 mg/day; range, 40-500) and from 40 long-term therapeutic users randomized to receive either placebo (N = 19) or diazepam (N = 21; mean diazepam dose equivalents, 15 mg/day; range, 5-40; mean duration of use, 72 months; range, 6 240) were analyzed. Information on the type and severity of symptoms was obtained from several assessment instruments. In the high-dose abuse group, plasma benzodiazepine concentrations were measured daily and the 3 consecutive days of greatest relative daily fall were considered the critical withdrawal period. Selection of the 22 items of the Clinical Institute Withdrawal Assessment Benzodiazepines (CIWA-B) was based on statistically significant differences between baseline and critical withdrawal periods in high-dose subjects and between symptoms associated with placebo and diazepam in low-dose subjects, using contingency tables and logistic regression analysis. Of the 104 symptoms measured by the assessment instruments, 22 symptoms were found to distinguish withdrawal from prewithdrawal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574195 TI - View from the nation's courts. PMID- 2574194 TI - The behavioral toxicity of bromocriptine in patients with psychiatric illness. AB - Dopamine agonists may be useful in the treatment of neuroleptic-induced hyperprolactinemia and movement disorders; it is a treatment approach that has been avoided for fear of inducing or exacerbating psychotic symptoms. The risks of giving dopamine agonists to psychiatric patients have been well documented in the literature. To further evaluate the psychotogenic effects of bromocriptine, a dopamine receptor agonist, we conducted a double-blind study in which 16 psychiatrically stable patients were treated for tardive dyskinesia with neuroleptics plus high doses of bromocriptine (N = 11) or placebo (N = 5) for 10 weeks. The diagnoses included schizophrenia, schizoaffective disorder, and major depression with psychotic features. Patients were evaluated weekly with the Brief Psychiatric Rating Scale and the Clinical Global Impression Scale during the 10 week treatment phase and for 8 weeks after medication was withdrawn. There were no statistically significant differences between active and placebo groups in behavioral ratings at baseline, week 10, and week 18. These results are compared with the findings of previous studies in which bromocriptine was given to psychiatric patients. Although the literature suggests that bromocriptine can induce or exacerbate psychosis in psychiatric patients, this occurs primarily in those with a psychotic diathesis and who are not currently receiving neuroleptic medication. Other important factors include the dose of bromocriptine, duration of treatment, and the clinical state of the patient at the time bromocriptine treatment is initiated. These results suggest that bromocriptine can be safely used in patients at risk for psychotic illnesses as long as patients are clinically stable and maintained on neuroleptics. PMID- 2574196 TI - Glutamate-positive neurons and axon terminals in cat sensory cortex: a correlative light and electron microscopic study. AB - Immunocytochemical methods were used to perform a correlative light and electron microscopic study of neurons and axon terminals immunoreactive to the antiglutamate (Glu) serum of Hepler et al. ('88) in the visual and somatic sensory areas of cats. At the light microscopic level, numerous Glu-positive neurons were found in all layers except layer I of both cortical areas. On the basis of the dendritic staining of Glu-positive cells, two major morphological categories were found: pyramidal cells, which were the most frequent type of immunostained neuron, and multipolar neurons, which were more numerous in layer IV of area 17 than in any other layer. A large number of Glu-positive neurons, however, did not display dendritic labelling and were considered unidentified neurons. Counts of labelled neurons were performed in the striate cortex; approximately 40% were Glu-positive. Numerous lightly stained punctate structures were observed in all cortical layers: the majority of these Glu-positive puncta were in the neuropil. After resectioning the plastic sections for electron microscopy it was observed that: 1) the majority of neurons unidentifiable at light microscopic level were indeed pyramidal neurons except in layer IV of area 17, where many stained cells were probably spiny stellate neurons. Some Glu positive neurons, however, exhibited clear ultrastructural features of nonspiny nonpyramidal cells; 2) all synaptic contacts made by Glu-positive axon terminals were of the asymmetric type, but not all asymmetric synaptic contacts were labelled. The vast majority of postsynaptic targets of Glu-positive axons were unlabelled dendritic spines and shafts. The present results provide further evidence that Glu (or a closely related compound) is probably the neurotransmitter of numerous excitatory neurons in the neocortex. PMID- 2574197 TI - Catecholamine-containing neurons in the sheep brainstem and diencephalon: immunohistochemical study with tyrosine hydroxylase (TH) and dopamine-beta hydroxylase (DBH) antibodies. AB - The present study describes the distribution and morphological characteristics of neurons and nerve fibers containing the catecholamine-synthesizing enzymes, tyrosine hydroxylase and dopamine-beta-hydroxylase, in the sheep brainstem and diencephalon on the basis of immunohistochemical procedures. Neurons and fibers were considered to be dopaminergic if they showed anti-tyrosine hydroxylase immunoreactivity, without corresponding anti-dopamine-beta-hydroxylase immunoreactivity. The structures labeled with both antisera were considered noradrenergic or adrenergic. The distribution of catecholaminergic neurons corresponds to that described by other authors with similar methods in the rat and in primates. The noradrenergic neurons belong to cell groups A1 to A7 and the dopaminergic neurons to cell groups A8 to A15. In almost all studied areas, the catecholaminergic innervation is similar to that observed in the other species. However, the central catecholaminergic systems of the sheep showed some specific characteristics: (1) groups A3 and A4, described in the rat, were not found, (2) group A14 contains fewer neurons than in the rat, (3) group A15 does not contain a dorsal but only a ventral portion, (4) there is a larger dispersion of neurons within each group, especially A6 and A7, than in rodents, and (5) there is a larger noradrenergic innervation of the catecholaminergic groups than in the other species. PMID- 2574198 TI - Excitatory transmitter amino acid-containing neurons in the rat visual cortex: a light and electron microscopic immunocytochemical study. AB - The distribution and morphology of neurons labelled with antisera to glutamate or aspartate were examined, at the light and electron microscope levels, in the rat visual cortex. Using widely accepted light microscopic features as well as well established nuclear, cytoplasmic, and synaptic criteria, we noted that glutamate immunoreactive neurons were pyramidal cells distributed in layers II-VI, with an increased concentration in layers II and III. Aspartate immunoreactivity was localized chiefly to pyramidal neurons in layers II-VI. However, approximately 10% of immunolabeled cells were nonpyramidal neurons scattered throughout the cortex. Cell-body measurements revealed that, for both groups of neurons, layer V contained the largest labelled neurons, whereas layers IV and VI contained the smallest. Furthermore, in every layer, aspartate-stained neurons were larger than glutamate-positive cells. Finally, glutamate- and aspartate-labelled axon terminals formed asymmetrical synapses, which are presumably excitatory in nature, primarily with dendritic spines. These findings, together with recent detailed studies of the projections of glutamate- and aspartate-labelled cortical neurons, may provide essential background information for studies aimed to elucidate the function(s) of excitatory amino acids in the cortex and their role in pathological conditions. PMID- 2574200 TI - Factor XIIIa is expressed by fibroblasts in fibrovascular tumors. AB - Factor XIIIa (FXIIIa), a blood and intracellularly produced coagulation factor, has been found in a variety of cell types including fibroblast-like mesenchymal cells, and has been shown to stimulate the proliferation of fibroblasts and some neoplastic cells in vitro. We have already shown that the dendritic fibroblasts composing the fibrous papule contain this factor. We hypothesized that histopathologically similar fibrovascular tumors may also express FXIIIa and, in this report, show that the large stellate fibroblasts found in acquired digital fibrokeratomas, angiofibromas (adenoma sebaceum of Pringle), and oral fibroma (oral fibrous hyperplasia) also express FXIIIa. We postulate that FXIIIa, possibly acting as a growth factor, may be a common denominator in the pathogenesis of these tumors. Another possibility is that these tumors may be the consequence of a local overproduction of FXIIIa in response to an, as yet, unidentified stimulus. PMID- 2574199 TI - Comparative immunocytochemical study of the catecholaminergic and peptidergic afferent innervation to the dorsal vagal complex in rat and guinea pig. AB - Light and electron microscopic immunocytochemistry was used to study the fine structural organization of the catecholaminergic and hypothalamic peptidergic innervation of the dorsal vagal complex of the medulla oblongata in the rat and guinea pig, the latter of which is known to lack central adrenergic neurons. In the rat, adrenergic fibers immunoreactive to phenylethanolamine-N methyltransferase were concentrated in the dorsal motor nucleus of the vagus, where they established frequent symmetric synapses with dendrites and perikarya. On the other hand, the density of both oxytocin- and corticotropin-immunoreactive fibers appeared far lower in this nucleus than in the dorsal regions of the nucleus of the tractus solitarius, where they formed asymmetric synapses with small dendrites. In tissue treated for the dual labeling of two neuronal antigens, oxytocin- or corticotropin-reactive fibers were in close contact with adrenergic neurons in this dorsal medullary region. In the guinea pig, unlike the rat, the dorsal motor nucleus of the vagus contained large amounts of oxytocin- and corticotropin-reactive fibers, which formed many symmetric synapses with perikarya and dendrites. Taken together, these data suggest that the control of vagal preganglionic neurons by hypothalamic peptidergic neurons involves a bisynaptic neuronal pathway including adrenergic medullary neurons in the rat, whereas it is direct in the guinea pig, which lacks this adrenergic relay. PMID- 2574201 TI - Milking and feeding-induced release of the gastrointestinal hormones gastrin and somatostatin in dairy cows. AB - In monogastric animals, suckling influences the secretion of gastrointestinal hormones during lactation. The aim of the present study was to investigate whether similar effects are induced by milking in cows. Experiments were performed on four cows in midlactation. Blood samples were drawn from a chronic jugular vein catheter and gastrin, and somatostatin were determined by radioimmunoassay. Milking and feeding increased plasma gastrin. Somatostatin increased at morning milking and at feeding, but it decreased at evening milking. Atropine injected subcutaneously 30 min before milking increased resting concentrations of gastrin but decreased resting concentrations of somatostatin. Feeding-induced release of gastrin remained but the milking-induced release disappeared. The milking- and feeding-induced effect on somatostatin became more marked. We suggest that milking influences gastrin and somatostatin via activation of the vagal nerves. The gastrin release caused by milking may be mediated via a cholinergic mechanism, whereas the atropine resistant effect on gastrin caused by feeding and on somatostatin caused by both milking and feeding suggest that a noncholinergic, perhaps peptidergic, transmitter may be involved. PMID- 2574202 TI - Relation of neuroleptic and anticholinergic medication to cognitive functions in schizophrenia. AB - In this article, we review research designed to examine the influence of neuroleptic and anticholinergic drugs on cognitive processes in schizophrenia. The review is motivated by the recognition that pharmacotherapy is an important factor in psychological research on schizophrenia, given that the great majority of patients studied in investigations of cognition receive both of these drugs. We find that neuroleptic treatment is associated with limited normalization on many psychological measures, whereas anticholinergics appear to disrupt some aspects of memory. Subject selection criteria, research designs, and drug measurement methods important in the evaluation of possible drug effects in psychological studies are discussed. PMID- 2574203 TI - Skin-conductance orienting response in chronic schizophrenics: the role of neuroleptics. AB - The primary aim of this study was to determine whether there is an association between neuroleptic treatment and skin-conductance orienting response (SCOR) nonresponding in chronic schizophrenics. In a design adapted to this purpose, we were unable to demonstrate a relationship between neuroleptics and nonresponding. Although inability to prove the null hypothesis precludes a claim that neuroleptic treatment and SCOR nonresponding are unrelated, internal evidence and prior studies strongly suggest that such a dissociation exists in most chronic schizophrenic nonresponders. We also found stable nonspecific and toxic skin conductance activity differences between SCOR "responders" and "nonresponders" on three occasions of testing. We interpret our results as bearing on state and trait issues in chronic schizophrenics. PMID- 2574204 TI - Characterization of abnormal respiratory movements in schizophrenic, bipolar and mentally handicapped patients with typical tardive dyskinesia. AB - A population of 76 patients with typical tardive orofacial dyskinesia, and from which cases of respiratory disease had been excluded, were evaluated for abnormal respiratory movements. Such abnormality was present in 34 patients (45%), and was unrelated to age, sex or smoking habits. However, patients with respiratory movement disorder showed more severe orofacial dyskinesia and higher blood pressure. Putative pathophysiological processes implicated in this often unappreciated component of the tardive dyskinesia syndrome are discussed. PMID- 2574205 TI - The mechanisms of antibody-dependent killing mediated by lymphoid and myeloid cells are distinct based on different divalent cation requirements. AB - To further understand the mechanism(s) of antibody-dependent cell-mediated cytotoxicity (ADCC) by various effector populations, we have examined the extracellular Ca++ and Mg++ requirements for ADCC performed by lymphocytes, monocytes, polymorphonuclear leukocytes and peritoneal macrophages. We have used the anti-Fc gamma R-bearing hybridoma cell lines (HC) as self directed targets for ADCC to analyse the triggering ability of each of the three defined Fc gamma R; Fc gamma RI, Fc gamma RII, and Fc gamma RIII. Lymphocyte killing of the anti Fc gamma RIII bearing HC (HC 3G8) was Ca++ dependent, but Mg++ independent. In contrast, monocytes and PMN killed the anti-Fc gamma RI- (HC 32) and the anti-Fc gamma RII- (HC IV.3) bearing HC in a Mg++-dependent, Ca++-independent fashion. In addition, freshly prepared monocytes were able to kill HC 3G8 in a Mg++ dependent, Ca++-independent fashion, indicating that low levels of Fc gamma RIII may be functionally detected on monocytes. Peritoneal macrophages were able to kill all three of the anti-Fc gamma R bearing HC in a Mg++-dependent, Ca++ independent fashion. Thus, the same target is lysed by myeloid cells in the presence of Mg++ without Ca++ and by lymphoid cells in the presence of Ca++ without Mg++. These results suggest that at least two distinct mechanisms of ADCC exist that depend on the type of effector cell mediating antibody-dependent killing and not necessarily on the Fc gamma R type triggered. PMID- 2574206 TI - Tumor necrosis factor stimulates transcription of HIV-1 in human T lymphocytes, independently and synergistically with mitogens. AB - We have investigated the effect of TNF, a cytokine produced during most immunologic and inflammatory reactions, on HIV genome expression in human T lymphocytes. A CD4+ human T cell line (J.Jhan) was transfected with vectors permitting the expression of the chloramphenicol acetyl transferase (CAT) gene under the control of the long terminal repeat (LTR) of HIV-1. rTNF was found to induce HIV LTR transactivation as intensely as PHA or phorbol esters. PHA enhanced TNF receptor expression in J.Jhan cells and acted synergistically with TNF on HIV LTR induction. TNF was also shown to induce well expression of a whole HIV provirus genome transfected into J.Jhan cells. The use of various CAT constructs carrying fragments of the HIV LTR, combined with bandshift assays, showed that TNF stimulates HIV transcription by acting on the kB-like enhancer element of the LTR through induction and/or activation of an NF-kB-like protein factor. Such findings are compatible with the hypothesis that TNF production participates in the pathogenesis of AIDS by enhancing HIV replication in T lymphocytes. PMID- 2574207 TI - A CD4 cell is capable of transferring suppression of collagen-induced arthritis. AB - Collagen-induced arthritis can be suppressed by i.v. injection of intact type II collagen (CII) but not type I collagen before immunization. To identify the mechanism mediating this suppression, splenocytes were obtained from mice injected with CII or OVA and administered to recipients that were subsequently immunized with CII. Mice receiving cells from donors injected with CII had a lower incidence of arthritis and lower antibody titers than those receiving cells from OVA-injected donors. Treatment of cells with 3000 rad of gamma-irradiation abrogated the suppression. To determine the phenotype of these donor cells, spleen cells were fractionated by adherence to plates coated with mouse anti-IgG to enrich for Thy-1+ phenotype. Thy-1+ cells injected into naive mice could significantly suppress arthritis. Further depletion of T cell subsets by panning revealed that depletion of CD4+ cells prevented the transfer of suppression whereas removal of CD8+ cells had no effect. Isolated CD4+ cells transferred into naive mice were also suppressive. Recently the Pgp-1 (Ly-24) Ag has been described to identify a unique memory subset of CD4+ cells when present on the cell surface. In CII-tolerized spleen populations, removal of the Pgp-1+ (Ly-24) subset of T cells abrogated suppression and transfer of isolated Pgp-1+ cells suppressed arthritis. These findings indicate that the Pgp-1+ subset of CD4+ cells can suppress collagen-induced arthritis and suggest that a CD4+ memory cell down-regulates autoimmunity. In addition, treatment of donor animals with cyclosporin, which inhibits the development of CD4+ cells, abrogated suppression. PMID- 2574209 TI - [Clinical usefulness of the combination assay of CA 125, SLX, and CA 72-4 in patients with ovarian cancer]. AB - A serological diagnosis of ovarian carcinoma was performed using a combination assay consisting of three tumor markers. Cancer Antigen 125 (CA125), Sialyl Lex-i (SLX), and CA72-4. The results were compared with those for the individual tumor markers. Furthermore, the diagnostic accuracy of the combination assay was compared with that of image diagnosis in patients with stage I ovarian carcinoma. 1. The combination assay was positive in 90.3% of the patients with ovarian carcinoma. Classified according to the clinical staging system, the positive rate increased progressively with each stage, 77.6% in stage I, 92.0% in stage II, 98.5% in stage III, and 100.0% in stage IV. According to histological types, the positive rates were 93.8% in serous cystadenocarcinoma, 87.0% in mucinous cystadenocarcinoma, 88.9% in endometrioid carcinoma, and 85.7% in clear cell carcinoma. On the other hand, 6.9% of healthy persons and 38.6% of patients with various benign diseases were found to be false positive in this diagnosis. The high false-positive rate in the latter group is thought to result from the high false-positive rate of 73.5% and 57.1% for adenomyosis and pelvic endometriosis, respectively. 2. The accuracy of the image diagnosis and combination assay was compared in 58 cases with stage I ovarian carcinoma. Both procedures were positive in 38 cases (65.5%). Two cases (3.4%) were positive in image diagnosis but negative in the combination assay. Seven cases (12.1%) were negative in image diagnosis but positive in the combination assay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574208 TI - The Ir-Thy-1 concept: a swan song. PMID- 2574210 TI - [Type III and type IV allergy: granulomatous lung disorders]. PMID- 2574211 TI - Immobilization of alveolar macrophages for measurement of in vitro dissolution of aerosol particles. AB - The dissolution of aerosol 57CO3O4 particles was investigated by exposing baboon alveolar macrophages (AM) to the particles and immobilizing the AM in alginate macrobeads crosslinked with Ca2+ ions. AM were obtained from bronchopulmonary lavage and, after immobilization, were stored in culture medium enriched with Ca2+. Dissolution of 57Co3O4 particles by these AM was measured for up to 16 days by gamma counting of filtered media containing beads. For these particles, the daily dissolution rate was 0.242 per cent versus 0.072, 0.089 and 0.091 per cent for beads containing particles only, particles combined with AM enzymes, and non phagocytic cells, respectively. The rate obtained with immobilized AM is very close to the rates previously found for adherent AM in culture. Moreover, AM that had phagocytosed PuO2 particles before immobilization by the same method gave a mean daily dissolution rate close to that obtained in vivo with baboons. We also demonstrated, by dissolving the alginate network, that immobilization did not affect AM viability. The present method of immobilization seems very promising compared to conventional methods because it facilitates manipulation, allows the use of cells at a high density in a small volume, and gives results for particles with a very low dissolution rate. PMID- 2574212 TI - Manipulation of the radiosensitivity of pig epidermis by changing the concentration of oxygen and halothane in the anaesthetic gas mixture. AB - A gas mixture of halothane, oxygen and nitrous oxide has been used to anesthetize pigs for irradiation. The effects of various concentrations of halothane and oxygen on the radiosensitivity of the epidermis were examined after irradiation with single doses of beta-rays from strontium-90 plaques. The incidence of moist desquamation was used as an endpoint, and experiments were compared on the basis of the dose associated with a 50 per cent incidence of moist desquamation (ED50 +/- SE). For pigs inspiring an anaesthetic gas mixture of 2 per cent halothane, approximately 70 per cent oxygen and approximately 30 per cent nitrous oxide the ED50 for moist desquamation was 27.32 +/- 0.52 Gy. A similar ED50 value of 27.39 +/- 1.20 Gy was obtained when 4 per cent halothane was used in place of 2 per cent. When the pigs were breathing air (approximately 21 per cent oxygen) in place of oxygen and nitrous oxide the ED50 values were increased significantly to 31.25 +/- 0.94 Gy and 33.72 +/- 1.08 Gy for 2, and 4 per cent halothane, respectively. This change in the radiosensitivity of the epidermis was represented by dose modification factors of approximately 1.13 and approximately 1.23 for 2 and 4 per cent halothane, respectively. Irradiation with a high oxygen concentration in the inspired gas mixture did not result in any significant variation of the dose required to produce moist desquamation in 50 per cent of the fields irradiated for dorsal, lateral and ventral positioned skin fields on the flank. However, pigs breathing air and halothane during irradiation showed marked differences in the radiosensitivity of the various sites on the flank, with ED50 values for moist desquamation of approximately 37 Gy and 26-30 Gy for dorsal and ventral positioned fields, respectively. This marked difference in radiosensitivity suggests variations in the physiological compensation over the flank when pigs are breathing oxygen at low concentrations under anaesthesia. PMID- 2574213 TI - Thermal and physiological changes in rats exposed to CW and pulsed 2.8 GHz radiofrequency radiation in E and H orientations. AB - Ketamine-anesthetized Sprague-Dawley rats were exposed in both E and H orientations to far-field 2.8 GHz continuous-wave (CW) and pulsed (0.5 microseconds, 500 pps) radiofrequency radiation (RFR) at equivalent whole-body average specific absorption rates (SAR) of approximately 14 W/kg. Intermittent irradiation was performed in all four exposure conditions, in the same animal, to repeatedly increase colonic temperature from 38.5 to 39.5 degrees C. Tympanic, subcutaneous (sides toward and away from RF sources), colonic, and tail temperatures, electrocardiogram, arterial blood pressure, and respiratory rate were continuously recorded. The results revealed no significant difference between the thermal effects of CW and pulsed RFR exposure. The results did show significant differences between the thermal effects of E- and H-orientation exposure. H-orientation irradiation produced significantly faster colonic temperature increases and, with the exception of the tail, produced significantly greater localized heating in the anesthetized rat, and higher local SAR in rat carcasses than did E-orientation exposure. Under all exposure conditions, heart rate and blood pressure increased significantly during irradiation and returned to baseline when exposure was discontinued. Respiratory rate remained unchanged during irradiation. There were no significant differences between the effects of E- and H-orientation exposure, or between CW and pulsed irradiation, upon heart rate, blood pressure, and respiratory rate. PMID- 2574214 TI - The 5Rs of radiobiology. PMID- 2574215 TI - Lack of correlation between radiosensitivity and inhibition of DNA synthesis in hybrids (A-T x HeLa). AB - Hybrid cells obtained from A-T and D98/AH(HeLa) cells showed normal radiation sensitivity to cell killing, but retained radioresistant DNA synthesis similar to parental A-T cells. PMID- 2574216 TI - Responses of two mammalian cell lines to low gamma-ray doses. AB - We have observed that low gamma-ray doses regularly improve the survival (plating efficiency) above that of unirradiated control cultures, which we postulate could arise through inducible DNA repair, and would have profound effects on the interpretation of cell culture experiments. PMID- 2574217 TI - Increase in intracellular cysteine after exposure to dithiothreitol: implications in radiobiology. AB - Dithiothreitol reduces cystine in tissue-culture medium, and the resulting cysteine is accumulated in Chinese hamster V79 cells to an extent which should be taken into account in evaluating models of radiosensitivity and the effects of thiol radioprotectors. PMID- 2574218 TI - Measurement of the G-value for 1.5 keV X-rays. AB - Although there are several theoretical predictions of the dependence of the G value on X-ray energy, measurements have not been made below approximately equal to 7 keV. Using a ferrous sulfate solution modified by the addition of benzoic acid, we have measured the relative G-values for Alk characteristic X-rays (1.5 keV), 238Pu alpha-particles (3.7 MeV), 60Co (1.17 MeV) and 137Cs (0.66 MeV) gamma rays. This modified ferrous sulfate solution gave a 4-fold increase in sensitivity relative to the conventional solution, making measurements with the Alk X-rays feasible. The relative ferrous-to-ferric conversions as a function of dose were similar for the two gamma-ray energies, yielding G-values of 1.62 and 1.59 mumol J-1 for the 60Co and 137Cs radiations, respectively. The alpha particle G-value was 0.52 mumol J-1, or 31 per cent of that for the 60Co gamma rays, in good agreement with previous measurements. The Alk X-rays had a G-value of 0.92 mumol J-1 or 57 per cent of that of the 60Co radiation. This G-value for the 1.5 keV X-rays is within 20 per cent of the values predicted by current theories, and theoretical values are within the error range of our measurement. The consistency between the experimental value reported here and theoretical G values for ultrasoft X-rays should be valuable for models of radiation action on biological systems. PMID- 2574219 TI - Molecular electrostatic potential studies on some nitroimidazolyl and nitroheterocyclic compounds. AB - The electronic wave functions of 11 nitroimidazolyl and nitroheterocyclic compounds were computed using the CNDO/2 quantum chemical method. The location of the greatest nucleophilic reactivity for each molecule was predicted to be mostly near or on the nitro group. As in our previous publication (Lin Liming et al. 1985) the maximum values of the superdelocalizability index for nucleophilic reactivity S(N)max and the sum of S(N)r for each of these compounds were discovered to be significantly correlated with the radiosensitivity as indicated by log(1/C1.6), where C1.6 is the concentration of the compound required to achieve an enhancement ratio of 1.6. The electrostatic potential distribution on a plane parallel to the plane of the imidazole or heterocyclic ring was computed for these compounds with the wave functions obtained from CNDO/2 calculations. In order to analyse the steric electrostatic potential maps, the overall electrostatic potential on an imaginary surface surrounding a molecule was calculated using the multicentre multipole expansion method. It was found that a wide and deep negative potential area exists in a compound which had significant radiosensitizing efficiency, while in metronidazole, which is not an efficient radiosensitizer, the corresponding area is narrow. This phenomenon may be related to the interaction between these compounds and certain biological macromolecules. These preliminary quantum chemical results support Adams' electron affinity theory, and might be helpful in searching for new radiosensitizers. PMID- 2574220 TI - Gamma and pulse radiolysis investigation of the reaction of desferrioxamine with superoxide anions. AB - The kinetic scheme of the reaction of desferrioxamine (DFO) with O2-. was studied using pulse and gamma-radiolysis. The rate constant k(O2-. + DFO) is equal to 1.3 +/- 0.1 x 10(6) dm3 mol-1s-1 at pH 7.4. Studying the competition between DFO and ferricytochrome-c for O2-. generated by gamma-radiolysis, we observed that the nitroxide free radical resulting from the reaction of O2-. with DFO and the product(s) resulting from the decay of this nitroxide radical act inversely towards the cytochrome-c-Fe3+/cytochrome-c-Fe2+ redox couple. This explains the discrepancy between our value of k(O2-. + DFO) and the one measured previously using ferricytochrome-c for the detection of O2-. The reported results show that DFO acts as a powerful O2-. scavenger, and that the products resulting from the reaction of DFO with O2-. can initiate oxidative and/or reductive reactions that should be taken into account in interpreting the effects of DFO in vitro and in vivo. PMID- 2574221 TI - Ultraviolet difference spectral studies in the gamma radiolysis of DNA and model compounds. I. Aqueous solutions of DNA bases. AB - Ultraviolet difference spectra of gamma-irradiated, air-saturated aqueous solutions of DNA bases vs. unirradiated solutions of the same bases are shown to be a very sensitive supplemental tool with which to investigate the yields, postirradiation kinetics, and general nature of DNA base radiation products. Irradiated pyrimidines yield difference spectra which are approximately negative mirror-images of the base absorption spectra in the near-UV, indicating loss of ring conjugation. Difference spectra of irradiated purines yield a more complex pattern containing a positive long-wavelength peak, interpreted as radiation induced extension of conjugation of the pi electron system beyond that of the unirradiated purine. On the basis of the spectroscopic evidence from these studies, 8-hydroxyguanine appears to be the dominant UV-absorbing radiation product in air-saturated guanine solutions with a G-value of 0.3 molec (100 eV) 1. Difference spectral studies provide isosbestic points which can be used in testing proposed radiation products and their yields. Such spectral studies are a rapid, non-invasive, supplemental tool which can be employed in conjunction with other analytical techniques in radiation-chemical studies, and which is one of the few tools able to detect short-lived chemical intermediates observed in oxygenated solutions of irradiated purines. PMID- 2574222 TI - Non-linear dose-effect curve for DNA double-strand breaks by low LET radiation: the effect of eluting buffer composition on the measurement of breaks by the filter elution technique. AB - Chinese hamster V79 cells were irradiated with 250 kVp X-rays and analysed for the presence of DNA double-strand breaks using filter elution. Changing the pH of the elution and lysis buffers from pH 9.6 to 7.2 leads to a decreased rate of elution of the DNA from the filters and a small difference in the dose-effect relationship obtained. In both cases the dose-effect curves were non-linear. When cells are irradiated with 238Pu alpha-particles a difference in the rate of elution of the DNA is also observed between the two pH values, although the dose effect curves are linear. These findings suggest that there may be qualitative differences in the types of lesions being induced by low-LET radiation and being scored as dsb in the filter elution assay at pH 9.6. However, carrying out elution at pH 7.2 does not eliminate the nonlinear response measured after X irradiation. PMID- 2574223 TI - Use of damaged plasmid to study DNA repair in X-ray sensitive (xrs) strains of Chinese hamster ovary (CHO) cells. AB - The effect of gamma-irradiation of pSV2gpt DNA on its transfection frequency has been analysed using CHO xrs mutants. Xrs mutants are sensitive to ionizing radiation and show a defect in double-strand break (dsb) rejoining. At low doses a sharp decrease in relative transfection frequency, i.e. transfection frequency of irradiated plasmid relative to untreated plasmid, was observed in the xrs mutants compared with the parent line K1. Electrophoresis of the irradiated plasmid DNA showed that the decrease in transfection frequency in the xrs mutants correlated with the change of supercoiled molecules into open-circular forms. One explanation for these results is that the xrs gene could play a part in the integration or repair of open-circular molecules produced by gamma-radiation. In the parent line CHO-K1, open-circular and supercoiled molecules have the same transfection frequency. The effect of linearization of pSV2gpt DNA by restriction enzymes on transfection frequency in xrs and wild-type strains has also been examined. In contrast to the above results we have not detected a difference in the relative transfection frequency between xrs and wild-type strains. The results suggest that restricted plasmid DNA is subject to extensive nucleolytic degradation, and this occurs to equal extents in wild type and mutant strains. PMID- 2574224 TI - Nuclear lysate sedimentation measurements of peripheral blood lymphocytes from radiotherapy patients. AB - When isolated nuclei of human lymphocytes are challenged with 2 M NaCl a histone free-DNA-protein (HF-DNA) complex is released. In a linear sucrose gradient (pH 8.0) the sedimentation distance of HF-DNA is reduced when immediately isolated from cells irradiated in vitro. At low doses, if irradiated cells are incubated at 37 degrees C the sedimentation behaviour approaches that of unirradiated cells (i.e. repair). In the present study such repair was usually complete within 1 h. The radiation damage to lymphocytes from a healthy donor group and three patient groups consisting of new patients (before radiotherapy), well patients (2 to 6 years post-radiotherapy) and patients with complications attributed to radiotherapy was similar. The lymphocytes from most healthy donors and new patients demonstrated complete repair of radiation damage following an incubation of 1 h at 37 degrees C. However, 2/29 (6.9 per cent) healthy donors and 2/25 (8 per cent) new patients demonstrated poor repair. Of those patients now attending with 'bowel complications' attributed to radiotherapy 7/16 (44 per cent) demonstrated poor repair. In contrast, all those (11/11) described as 'well and complication-free' showed good repair. PMID- 2574225 TI - Induction of chromosome aberrations in human lymphocytes by monochromatic X-rays of quantum energy between 4.8 and 14.6 keV. AB - The induction of chromosome aberrations was studied in human peripheral blood lymphocytes irradiated in vitro with synchrotron-produced monochromatic soft X rays of quantum energy in a range between 4.8 and 14.6 keV. These X-rays were more effective in producing chromosome aberrations (dicentrics and rings) than 60Co gamma-rays. The efficiency increased with increasing LET of the photoelectrons and their associated Auger electrons, reaching a maximum at a track average LET (L delta = 100, T) of around 4 keV/microns, and tended to decrease or become rather refractory with further increase of LET. This unique LET dependency was consistent with the dual nature of chromosome aberration formation, and interpreted as a reflection of a limited range of photoelectrons as compared with the size and intranuclear geometry of the elemental chromatin fibres as vehicles of damage interaction. PMID- 2574226 TI - Cell density dependence of transformation frequencies in C3H10T1/2 cells exposed to X-rays. AB - The effects of cell density on transformation frequencies were studied in C3H10T1/2 cells exposed to 0.5 and 7 Gy of 200 kVp X-rays. Initial cell density strongly influenced transformation frequency; this decreased by a factor of between 4 and 10 when the initial seeding density was changed from 50 to 2500 cells/10 cm diameter Petri dish. The data were fitted with two equations: (a) an allometric function represented on a log-log scale by a straight line and (b) a sigmoidal function with plateaux between 50 and 250 cells/dish and above 600. The two curves are compared and their probabilities discussed. Our data indicate that the region between 50 and 250 cells/dish would be the most suitable region for dose-effect measurements. A study of the growth curves at 0.5 and 8.5 Gy shows that cell growth rates are not influenced by initial cell density. PMID- 2574227 TI - Lethal mutations, the survival curve shoulder and split-dose recovery. AB - Our group has shown that many of the progeny of cells which survive irradiation, as determined using a clonogenic assay, die out after 8-30 further cell divisions. Correction of conventional survival curves for this extra component of defective cells (termed lethally mutated cells) reduces or eliminates the 'shoulder' which is characteristic of the radiation response of many mammalian cell lines. Since the size of the shoulder is theoretically and experimentally linked with the extent of split-dose recovery, this paper examines the occurrence of lethal mutations following fractionated irradiation using a variety of experimental conditions. The results show that, when curves are corrected for lethal mutations to give residual survival, the size of the single-dose survival curve shoulder is indeed reduced but the extent of recovery after split-dose irradiation remains the same or, under some conditions, is actually increased. However, the rate of increase in survival with time between doses is reduced over the first 2 h if the data are corrected for lethal mutations, suggesting that early postirradiation repair may be error prone. When a metabolic inhibitor which depletes cellular ATP was used, the single-dose and split-dose curves corrected for lethal mutations were coincident with each other and with the corrected single-dose control curve, all being exponential and with an extrapolation number of one. It is concluded that the mechanisms leading to the production of the primary survival-curve shoulder are different from those leading to split-dose recovery. The results strongly suggest that a mechanism involving induction of repair/resistance by an initial dose of radiation is involved in split-dose recovery. PMID- 2574228 TI - The selective attention deficit in schizophrenia. Limited resources or cognitive fatigue? AB - The Stroop Word-Color Test was used to study selective attention deficits in schizophrenic and nonschizophrenic psychiatric patients, compared with nonpsychiatric control subjects. Parts of the Weschler Memory Test and a shortened version of the Stroop Test were administered to test the hypotheses that the attentional deficit could be explained by problems of memory or cognitive fatigue. All patients showed deficits on all of the Stroop scales, but closer analysis of the results permitted discrimination of schizophrenic from nonschizophrenic patients. Schizophrenic patients showed as much difficulty as nonschizophrenic subjects on a limited-duration selective-attention task, but deteriorated significantly more when selective attention had to be maintained. The results could not be attributed to memory problems in the schizophrenic group. The results support the existence of two separable selective attention deficits in schizophrenic patients: a difficulty in selectively attending to the salient aspect of a complex stimulus, a difficulty shared with nonschizophrenic subjects, and a difficulty in maintaining selective attention over time that seems to be more marked in schizophrenic subjects. PMID- 2574229 TI - Carbamazepine adjunct for nonresponsive psychosis with prior hallucinogenic abuse. AB - Some patients diagnosed as schizophrenic report persistent polymodal hallucinosis following a period of extensive hallucinogenic drug abuse unrelieved by the usual antipsychotic drugs. In this open study, carbamazepine (Tegretol, an anticonvulsant) was administered to three patients with polymodal hallucinosis which had failed to diminish on antipsychotic drugs alone. All three patients showed a marked to complete reduction in symptomatology. PMID- 2574230 TI - Striatal dopamine D2 receptors in tardive dyskinesia: PET study. AB - The dopamine D2 receptors were investigated in vivo in eight neuroleptic-free patients with persistent tardive dyskinesia using positron emission tomography and 76Br-bromospiperone. The striatal receptor density, estimated by the striatum/cerebellum radioligand concentration ratio, was not elevated in patients as compared with age-matched controls but was positively correlated with the severity of orofacial dyskinesia assessed with the Abnormal Involuntary Movement Rating Scale. These results indicate that tardive dyskinesia is associated with normal levels of striatal D2 receptors but the severity of orofacial movements may depend on the relative density of striatal D2 receptors. PMID- 2574231 TI - Noradrenaline enhances temporal auditory contrast and neuronal timing precision in the cochlear nucleus of the mustached bat. AB - In the mustached bat, Pteronotus parnellii, noradrenaline (NA) was applied iontophoretically to single units in the anteroventral cochlear nucleus. NA suppressed tonic components of auditory responses and enhanced phasic onset responses to pure tone stimuli. The enhancement of onset activity was most pronounced in awake bats and was due to a decrease in the latency jitter of the first tone-evoked spikes from 0.55 msec in controls to 0.28 msec during NA application. In addition, NA reduced spontaneous neuronal activity. Noradrenergic antagonists suppressed phasic onset activity and increased the latency jitter of onset spikes. Opposite to the effect of NA, the tonic response component increased during application of the beta-antagonist propranolol but decreased during injection of the alpha 1-antagonist corynanthine. Other putative transmitter substances tested, nonselectively depressed both phasic and tonic response components (GABA, glycine) or increased both components either similarly or had more pronounced effects on the tonic response components (ACh, glutamate). Thus, NA specifically enhances auditory temporal contrast in favor of transients and improves neuronal timing precision, which may be of relevance for auditory tasks like passive sound localization, echolocation, and recognition of temporal patterns. PMID- 2574233 TI - The relationship between cerebral palsy and cryptorchidism. AB - This study examined the reported association between cerebral palsy and cryptorchidism. A comparison was made among 25 boys with cerebral palsy under the age of 2 years and 6 months, 25 boys with cerebral palsy aged between 5 and 10 years, and age-matched controls. The testes remained in the same position with age in boys with cerebral palsy, whereas in normal children the testes were slightly lower initially (P less than .005) and became lower still with growth (P less than .001). This result, taken in conjunction with previous studies, casts doubts on the theories of early damage to the hypothalamic-pituitary-gonadal axis as the cause of maldescent in cerebral palsy. It is postulated that any apparent increase in cryptorchidism in older patients with cerebral palsy may be caused by spasticity of the cremaster muscle leading to pathologic retraction of the testis out of the scrotum. PMID- 2574232 TI - Lymphocyte status in endomyocardial biopsies and blood after heart transplantation. AB - We performed immunological phenotyping of mononuclear cells in tissue sections of 84 endomyocardial biopsies (EMB) showing infiltrates, which were taken from 21 patients after heart transplantation. Data were correlated with histology (grading following Billingham) and cyto-immunologic monitoring (CIM) on blood samples (grading into negative, rejection, or infection, based on leukocyte morphology and T-cell phenotype). Few T lymphocytes were observed in 35 biopsies, and many in 49 biopsies. The semi-quantitative estimate of T cells and CD4/CD8 ratio did not correlate with EMB histology but was related to CIM data. For example, 31 out of 42 cases with a CIM indicative of infection (14 of which showing no rejection on histology) manifested large numbers of T cells. In most cases, the CD4/CD8 ratio was less than 1. The presence of activated cells (bearing interleukin-2 receptors or the CD30 antigen) was not related to EMB histology or to CIM data. The number of T cells (subsets) in EMB was not related to relative or absolute numbers in the blood. PMID- 2574235 TI - Management of benzodiazepine withdrawal. PMID- 2574234 TI - Detection of cathepsin B- and L-, elastase-, tryptase-, trypsin-, and dipeptidyl peptidase IV-like activities in crevicular fluid from gingivitis and periodontitis patients with peptidyl derivatives of 7-amino-4-trifluoromethyl coumarin. AB - Crevicular fluid samples were collected from 20 gingivitis and periodontitis patients using filter paper strips; these were then eluted into buffer. Portions of each sample were combined and the activities of this pooled eluate against different peptidyl derivatives of 7-amino-4-trifluoromethyl coumarin (AFC) were examined with respect to their pH profiles and effector responses. Ca-thepsin B- and L-like activity was detected with Bz-Val-Lys-Lys-Arg-AFC; elastase-like activity with MeOSuc-Ala-Ala-Pro-Val-AFC; tryptase-like activity with Z-Ala-Ala Lys-AFC; trypsin-like activity with Z-Gly-Gly-Arg-AFC; and dipeptidyl peptidase (DPP) IV-like activity with Ala-Pro-AFC. The selectivity and sensitivity of these assays were improved by choice of appropriate conditions. The cathepsin B- and L , elastase-, tryptase-, and trypsin-like activities all had properties consistent with those from host sources, whilst partial inactivation of the DPP IV-like activity by heat treatment (60 degrees C for 30 min) suggested that it may have represented a mixture of human and Bacteroides gingivalis enzymes. Individual patient eluates showed wide variations in enzyme concentrations, but generally elastase-like activity was by far the highest. The sensitivity of the assays with AFC-linked substrates was such that it should prove possible to measure all five different types of activity in crevicular fluid samples from local periodontal disease sites. PMID- 2574236 TI - Two classes of [3H]spiperone binding sites in bovine neurohypophysis: D-2 receptors and putative 5-HT2 receptors. AB - Binding of [3H]spiperone was studied in membranes obtained from bovine neurohypophyses devoid of intermediate lobe tissue. Non-linear Scatchard plot suggested the presence of more than a single class of binding sites. Competition experiments using ketanserin, a ligand selective for 5-HT2 receptors, were carried out to ascertain whether serotonergic, in addition to dopaminergic receptors, might be responsible for the heterogeneity of [3H]spiperone binding. Computer-assisted modeling suggested the presence of two classes of binding sites for ketanserin (Kd = 1.6 +/- 0.2 and 366.7 +/- 20.5 nM, respectively). The Kd value for ketanserin binding to the high-affinity sites, as well as the Kd of [3H]spiperone for these sites suggested by the 2 sites model indicate that they represent serotonin 5-HT2 receptors. The [3H]spiperone Kd at the ketanserin low affinity sites (65 +/- 7 pM) and the rank order of inhibitory potencies for several antagonists show that the low-affinity sites represent dopamine D-2 receptors. PMID- 2574237 TI - Quantitative comparison of bromoacetylated derivatives of alprenolol and pindolol on beta-adrenergic receptor binding and mobility in S49 cells. AB - The reactivities with beta-adrenergic receptors of the bromoacetyl derivatives of the beta-adrenergic antagonists alprenolol and pindolol, BAAM and BIM, respectively, were compared in intact S49 mouse lymphoma cells. Both compounds caused irreversible blockade of receptors and changes in the mobility of the remaining non-modified receptors. BIM proved to be an irreversible blocker of high potency, with an IC50 of 40-60 nM at 4 degrees C, whereas the IC50 for BAAM was 600-900 nM. Moreover, treatment with both compounds resulted in an inhibition of internalization of non-modified receptors (IC50 = 200-300 nM for both). After treatment of desensitized cells which have internalized 50-60% of their surface receptors, with BIM or BAAM, receptor reappearance was found to be slowed down (IC50 about 100 nM for both compounds). The effects of the bromoacetylated antagonists on receptor internalization were apparently selective for beta adrenergic receptors, since binding and internalization of transferrin or low density lipoprotein were not affected. PMID- 2574238 TI - Parasuicide in central London 1984-1988. AB - Experience of a central London unit dedicated to the care of patients following parasuicide between 1984 and 1988 is reviewed. There were 1160 admissions, which accounted for 11% of all acute adult medical admissions. The female to male ratio was 1.3, with a peak rate for females below 25 years and for males between 20 and 35. Unemployment was found to be a risk factor for parasuicide in men. Benzodiazepines were the most frequently used drug in parasuicide (35%), followed by paracetamol (13%) and aspirin (9%). PMID- 2574239 TI - Quantitative determination of factors contributing to doxorubicin resistance in multidrug-resistant cells. AB - There is a large discrepancy between the changes in drug accumulation and the changes in drug cytotoxicity that accompany development of anthracycline resistance in multidrug-resistant cells. In our study, a quantitative relationship has been established between reversal of multidrug resistance by resistance modifiers and a concomitant decrease in intracellular levels of doxorubicin measured at equitoxic concentrations (IC50) in CHRC5 and 2780AD multidrug-resistant cells. (IC50 = concentration required for 50% growth inhibition.) We have demonstrated that resistance modifiers like verapamil and Ro 11-2933/001 act by increasing the effectiveness of intracellular doxorubicin, apparently by inducing redistribution of the drug from the cytoplasm to the nucleus of a multidrug-resistant cell, as shown by quantitative fluorescence microscopy. At complete reversal of resistance, as measured directly or inferred by extrapolation, the amount of intracellular doxorubicin at the IC50 as well as the ratio of nuclear doxorubicin to cytoplasmic doxorubicin were the same as those in sensitive cells. These results offer an explanation for the frequently observed discrepancies between drug accumulation and cytotoxicity and also show quantitatively that a decrease in drug accumulation and a change in intracellular drug distribution together are the only determinants of doxorubicin resistance in the multidrug-resistant cells studied. PMID- 2574240 TI - Developmental profile of glutamine synthetase in lines of mice bred for ethanol sensitivity. AB - Glutamine synthetase (GS) activity was used as a marker to examine differences in astrocyte development in mice selectively bred for ethanol sensitivity: long sleep (LS), short sleep (SS), mild ethanol withdrawal (MEW), severe ethanol withdrawal (SEW) and control ethanol withdrawal (CEW). We found that 1) GS activity in MEW and SEW was higher than in LS and SS during the first 2 weeks of postnatal development, in the forebrain but not in the cerebellum; 2) lower GS activity was observed consistently in all areas examined with the SS mice as compared to the LS; 3) glutamine synthetase activity in MEW and SEW differed significantly from their controls (CEW) during the early developmental period regardless of the brain region examined; however, after 30 days of maturation, GS activity in SEW was higher than that in MEW and CEW in the forebrain. Astrocytes are known to contribute in the regulation of the neuronal microenvironment. Therefore, we interpret the differences we found in astrocytic function during early brain development among these lines of mice to account in part for the neuronal predisposition to ethanol sensitivity. PMID- 2574241 TI - [The pathogenesis and treatment of renovascular hypertension]. PMID- 2574242 TI - [Clinical application of adrenoceptor blockers in the treatment of hypertension]. PMID- 2574243 TI - [Value of SLX and CA19-9 in the serum and tissue in colorectal cancer including the relation to Lewis blood type]. AB - This study was undertaken to determine the value of SLX and CA19-9 in the tissue and serum in colorectal cancer and adenoma including the relation to Lewis blood type. SLX isolated by Hakomori et al is one of sialyl SSEA-1 antigens characterized by type 2 chain lacto series glycolipids. Distribution of SLX and CA19-9 was determined in 137 specimens of colorectal cancer (107 advanced and 30 early cancer) and 20 specimens of adenoma by using immunoperoxidase (ABC) method. Serum SLX, CA19-9 and CEA levels were measured preoperatively in 58 cases with histologically proven colorectal cancer by using RIA kits. Simultaneously, Lewis blood type were determined by hemagglutination test in 31 cases. The following results were obtained; 1) SLX and CA19-9 were mostly observed in apical membrane and luminal contents, but a few in cytoplasma of cancer tissue. Positive rate of SLX and CA19-9 was 96.2% and 88.8%, respectively. 2) SLX and CA19-9 were lightly stained in the goblet cells and surface epithelium in some of the mucosa adjacent to the cancer tissue, and positive rate of SLX and CA19-9 was 24.3% and 32.7%, respectively. 3) Positive rate of SLX and CA19-9 was 60% and 50% in adenoma, and 94% and 80% in "m" cancer. Positive rate was not different due to grade of dysplasia of adenoma, but distribution of SLX or grade of the staining of CA19-9 was different between adenoma with mild and moderate dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574245 TI - Hepatic glutathione metabolism in mice acutely treated with lead acetate. AB - Hepatic glutathione content decreased in a dose-dependent manner after the administration of lead acetate (5-100 mg/kg, i.p.). Hepatic cysteine content, a substantial rate limiting factor in glutathione synthesis, also decreased transiently but significantly, whereas total cysteine (cysteine plus cystine) content remained unchanged. The pretreatment of mice with L-methionine (250 mg/kg, i.p.) partially prevented the decrease in glutathione content in lead treated mice at least partly through the elevation of hepatic cysteine content; in contrast, L-cysteine administration (250 mg/kg, i.p.) depleted hepatic glutathione contrary to a quick increase in hepatic cysteine content. The activity of gamma-glutamylcysteine synthetase (GCS), a rate limiting enzyme in glutathione synthesis, was not altered by either the administration of lead or sulfur amino acids. On the other hand, lead facilitated the disappearance of glutathione from the livers of mice treated with buthionine sulfoximine, a specific inhibitor of GCS. These lines of evidence suggest that for the decrease in glutathione content elicited by lead-loading, the increased efflux of glutathione into extra-hepatic spaces is a more crucial event than the fluctuation of intrahepatic cysteine concentration. PMID- 2574244 TI - The effect of prophylactic anti-asthma drugs on PAF-induced airway hyperreactivity. AB - Intravenous injection of platelet activating factor (PAF) in anesthetized guinea pigs induces non-selective airway hyperreactivity. This response to PAF was reduced in a dose-dependent manner by systemic administration of established prophylactic anti-asthma drugs (ketotifen, cromoglycate, aminophylline and glucocorticosteroids) and by competitive antagonists of PAF. These inhibitory effects could not be accounted for by antagonism of histamine (H1), serotonin or peptidoleukotrienes receptors; parasympatholytic activity; cyclo-oxygenase or lipoxygenase inhibition; mast cell stabilization; or bronchodilatation. Infusion or injection of PAF to induce airway hyperreactivity in the guinea pig may provide a prospective test for prophylactic anti-asthma drugs. PMID- 2574246 TI - [Immunohistochemical studies of putative neurotransmitters in the lower urinary tract]. AB - Putative neurotransmitters of the lower urinary tract were investigated in apes, rabbits and cats using immunohistochemical techniques of PAP (Peroxidase antiperoxidase) staining and IGSS (Immunogold silver staining) methods for Neuron specific enolase (NSE), Acetylcholine (Ach), Noradrenaline (NA), Vasoactive intestinal polypeptide (VIP), Substance P (SP) and Calcitonin gene related peptide (CGRP). 1) The localization of pelvic ganglions exhibited more striking evidence of species difference. Huge pelvic ganglions were found particularly in the dorsolateral area of the prostate in apes. On the other hand, in cats and rabbits, many ganglion cells were found around the uretero-vesical junctions. 2) In the pelvic ganglions of the apes, Ach immunoreactives were detected in nearly 70 percent of the cell bodies. 10-15 percent were NA immunoreactive cells. In addition, 15-20 percent VIP and a smaller percentage of SP immunoreactive cells were detected in the same ganglions. Axons extending from the ganglion cells showed the intense neurotransmitters immunoreactivity. 3) In the apes, varicose fibers containing SP were widely distributed in the epithelium, submucosa, muscle layer, and around the vessels of the bladder. SP immunoreactive cell bodies were found in the dorsal root ganglion at levels of L7, S1 and at the same levels in the posterior horn. On the other hand, the bulbourethral gland and the seminal vesicle contained SP immunoreactive cell bodies. 4) CGRP containing fibers were distributed in similar locations as SP containing fibers in the bladder. 5) VIP immunoreactive fibers were also widely distributed, being most dense at the base of the bladder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574247 TI - [Peculiarity of pulsed dye laser lithotriptor and its clinical application]. AB - Ultrasound lithotriptors (USL) and electrohydraulic lithotriptors (EHL) are representative lithotriptors for endoscopic elimination of upper urinary tract stones. However, they have some disadvantages. For example, USL can not be used with flexible scopes and EHL can cause unexpected tissue injury. To overcome these problems, the pulsed dye laser lithotriptor (MDL-1, Candera Co.) was developed. The characteristics of this laser lithotriptor and its direct effects on tissue was investigated. This pulsed dye laser lithotriptor generates a 504 nm wavelength green light beam by using a combination of a xenon flash lamp and the greenish dye composed of coumarin solution. The maximum output energy is 60 mJ/pulse and the pulse duration is 1.5 microsecond. The pulse rate can be varied from 1 to 20 Hz. First, the intensity of the shock wave was measured by using a combination of a piezoelectric element and an oscilloscope, and then, the results were compaired with those obtained by a similar experiment with an EHL. The average intensity of the shock wave was 54.4 mW under the conditions of 40 mJ/pulse of output energy and 10 Hz of pulse duration. On the other hand, the EHL generated an average of 54.7 W under the conditions of 400 mJ/pulse output energy. Then, fragmentation of various kinds of urinary stones in saline solution was performed. The results showed that this lithotriptor could fragment almost all kinds of stones except cystine stones. Then, hen's eggs were used to observe the effect if laser bean influenced on the organism immediately behind the photoradiated object. Only the egg shell was demolished but the egg membrane below the eggshell did not undergo any change. After these experiments, skin, liver, kidney and urinary bladder of nude mice and human prostatic urethral mucosa in case of TUR-P were irradiated by this laser. The results showed that laser energy caused slight penetration and localized hemorrhage from the surface of epithelium to subcutaneous tissue. It was confirmed that these effects were generated when the tip of the quartz fiber was in direct contact with the object.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574248 TI - [The postcholecystectomy syndrome and suppurative-inflammatory involvement of the biliary tract (apropos of the discussion held at the 16th Congress of Surgeons of the Ukrainian SSR)]. PMID- 2574249 TI - [Surgical correction of local thermoregulation of the downward-transposed testis in patients with cryptorchism]. PMID- 2574250 TI - [Introduction to the first symposium of the Ergophthalmologic Section of the Polish Ophthalmological Society]. PMID- 2574251 TI - [Formation of microbial biocenosis of wheat in a manned spacecraft]. AB - Mutual effects of microbial complexes of biological objects, men and their environment are of crucial importance for manned space missions. The present experiment to study wheat microflora flown in a manned spacecraft was a continuation of investigations the purpose of which was to identify the pattern of formation of microbial cenosis of higher plants in a closed ecological system. It was found that the microbial cenosis of plants grown during an early period of vegetation in space was formed under the influence of the anthropogenic factor. It was characterized by a high bacterial and fungal concentration of their phyllosphere and, to a lesser extent rhizosphere, occurrence of Escherichia coli representatives, and increased amount of cellulose-lytic bacteria. PMID- 2574252 TI - Prenatal diagnosis of cystic fibrosis: experience of two complementary methods. PMID- 2574253 TI - Prenatal diagnosis of cystic fibrosis using closely linked DNA probes. PMID- 2574254 TI - Genomic imprinting in hereditary glomus tumours: evidence for new genetic theory. AB - A study based on fifteen pedigrees showed that familial glomus tumours are inherited almost exclusively via the paternal line, a finding inconsistent with autosomal dominant transmission. The results can be explained in terms of the genomic imprinting hypothesis--the maternally derived gene is inactivated during female oogenesis and can be reactivated only during spermatogenesis. Genomic imprinting may have considerable implications for genetic counselling with respect to glomus tumours and also for the understanding of other hereditary diseases. PMID- 2574255 TI - Systemic glutathione deficiency in symptom-free HIV-seropositive individuals. AB - To find out whether systemic glutathione deficiency is associated with human immunodeficiency virus (HIV) infection, thus contributing to the immunodeficiency state, glutathione concentrations in venous plasma and lung epithelial lining fluid (ELF) of symptom-free HIV-seropositive and normal individuals were measured. Total and reduced glutathione concentrations in the plasma of the HIV infected subjects were about 30% of those in the normal individuals. Concentrations of these substances in the ELF of HIV-infected subjects were about 60% of those in the controls. There was no correlation between ELF and plasma concentrations of total or reduced glutathione. Since glutathione enhances immune function, glutathione deficiency may contribute to the progressive immune dysfunction of HIV infection. PMID- 2574256 TI - Relation between interatrial shunts and decompression sickness in divers. AB - The prevalence of right-to-left interatrial shunts was determined by contrast echocardiography in a blind comparison of 61 divers who had had decompression sickness, divided into four predetermined clinical subgroups, and a control group of 63 who had not. The prevalence of shunt was 15/63 in the controls and did not differ significantly in 24 divers with onset of neurological symptoms more than 30 minutes after surfacing (4/24) or 6 with joint pain only (1/6). In divers who had neurological symptoms within 30 minutes of surfacing the prevalence of shunt was 19/29, significantly higher. Rashes soon after surfacing were related to shunts but late rashes were not. PMID- 2574257 TI - Steroids and meningitis. PMID- 2574258 TI - Adolescent pregnancy. PMID- 2574259 TI - The trauma of being a patient. PMID- 2574260 TI - Smoke screen round the fetus. PMID- 2574261 TI - Recurrent erythema multiforme and herpes simplex virus. PMID- 2574262 TI - Open comparison of intramuscular chloroquine and quinine in children with severe chloroquine-sensitive falciparum malaria. AB - An open paired randomised comparison of intramuscular chloroquine (3.5 mg base/kg every 6 h) and intramuscular quinine (20 mg salt/kg followed by 10 mg/kg every 12 h) was carried out in 50 Gambian children with severe falciparum malaria. 8 children died, 6 from the quinine-treated and 2 from the chloroquine-treated group. Chloroquine reduced parasitaemia significantly more rapidly than did quinine, but other measures of the therapeutic response were similar in the two groups. Quinine injections were painful. These findings do not support the proposition that quinine is intrinsically superior to chloroquine in the treatment of severe drug-sensitive falciparum malaria. PMID- 2574263 TI - Value of urinary erythrocyte morphology in assessment of symptomless microhaematuria. AB - To assess the value of microscopic analysis of urinary erythrocyte morphology as the initial step in the investigation of patients with isolated symptomless microhaematuria, 316 consecutive patients were grouped according to whether they excreted eumorphic or mixed forms of erythrocytes or only dysmorphic forms. The former group was investigated fully, and urological disease was found in 85% of 123 patients. The 192 patients with exclusively dysmorphic erythrocytes in their urine and normal renal function (benign renal microhaematuria) were assigned to annual follow-up examinations of urinary red cell morphology and renal function, and subjected to invasive diagnostic procedures when a change was noted. In only 2 of the 132 patients followed up for at least 2 years did a new disease develop; this was easily identified at one of the annual examinations. Microscopic analysis of urinary erythrocyte morphology is therefore an effective method for identifying patients with symptomless microhaematuria needing specific diagnostic investigation. PMID- 2574264 TI - Close linkage of hypervariable marker DXS255 to disease locus of Wiskott-Aldrich syndrome. AB - Linkage analyses in 5 families with Wiskott-Aldrich syndrome show that a novel hypervariable locus, DXS255, is very closely linked to the disease gene on the proximal short arm of the X chromosome. DXS255, with a maximum lod score of 5.42 at theta = 0.00 (90% confidence interval 0.00, 0.10) and heterozygosity of over 90%, is likely to be the closest available marker to the Wiskott-Aldrich gene and to be helpful in genetic counselling of affected families. PMID- 2574265 TI - Euthanasia: a contemporary moral quandary. PMID- 2574266 TI - Gynaecologists' attitudes to abortion. PMID- 2574267 TI - Benefits of in-vitro fertilisation. PMID- 2574268 TI - Raised endothelial cell stimulating angiogenic factor in diabetic retinopathy. PMID- 2574269 TI - Painful peripheral neuropathy and cytomegalovirus pneumonia in AIDS. PMID- 2574270 TI - Hepatitis B: reactivation or reinfection associated with HIV-1 infection. PMID- 2574271 TI - Following up indeterminate HIV-1 western blots. PMID- 2574272 TI - Fatal toxic epidermal necrolysis after griseofulvin. PMID- 2574273 TI - Autonomic neuropathy in liver disease. PMID- 2574274 TI - Fish, diabetes, and the arterial wall. PMID- 2574275 TI - Aganglionic bowel in Hirschsprung's disease. PMID- 2574276 TI - Postoperative pyrexia, atropine, and malaria. PMID- 2574278 TI - Beware of the cow. PMID- 2574277 TI - Novel surgical approach to pseudotumour of ilium in haemophilia. PMID- 2574279 TI - Overpromotion of the dietary theory of coronary disorders. PMID- 2574280 TI - Weight in infancy and death from ischaemic heart disease. PMID- 2574281 TI - Antiglucocorticoid actions of dehydroepiandrosterone and low concentrations in Alzheimer's disease. PMID- 2574282 TI - Passive oral immunisation of children. PMID- 2574283 TI - Peripheral blood stem-cell transplantation in intensive treatment of multiple myeloma. PMID- 2574284 TI - Q-fever endocarditis. PMID- 2574285 TI - Cohort effect of HTLV-I seroprevalence in southern Japan. PMID- 2574286 TI - Smallpox vaccination for investigators. PMID- 2574287 TI - Prevalence of antibodies to hepatitis C virus in hepatocellular carcinoma. PMID- 2574288 TI - Saturation of fat and cholecystokinin release. PMID- 2574289 TI - Management of advanced prostatic cancer. PMID- 2574290 TI - Carotid sinus syncope induced by an orthodontic appliance. PMID- 2574291 TI - Quinolones in the environment. PMID- 2574292 TI - Selling patients' data. PMID- 2574293 TI - Computer-assisted diagnosis in acute abdominal pain. PMID- 2574295 TI - Subtypes of human papillomavirus 16 in cervical tissue. PMID- 2574294 TI - Mobilisation of lead by cisplatin. PMID- 2574296 TI - Stones and kilograms. PMID- 2574298 TI - Rapid screening for delta F508 deletion in cystic fibrosis. PMID- 2574297 TI - Menstrual effect on surgical cure of breast cancer. PMID- 2574299 TI - Cutaneous reactions in relation to the use of 'TED'-stockings. PMID- 2574301 TI - Extra payment for HIV-infected haemophiliacs. PMID- 2574300 TI - NHS reforms: a legal challenge. PMID- 2574302 TI - Mother-to-infant transmission of human immunodeficiency virus type 1: association with prematurity or low anti-gp120. AB - In a prospective study of pregnant women infected with human immunodeficiency virus type 1 (HIV-1) in Brooklyn, New York, USA, 16 (29%) of 55 evaluable infants were infected with HIV-1. 9 infants had paediatric acquired immunodeficiency syndrome, 6 had less severe clinical manifestations of HIV-1 infection, and 1 was symptom-free but was seropositive for HIV-1 beyond 15 months of age. The 10 infants born at 37 weeks of gestation or earlier were at higher risk of HIV-1 infection than infants born at 38 weeks of gestation or later (60% vs 22%) but the median age at appearance of disease was approximately 5 months in both groups. The HIV-1 transmission rate was not associated with predelivery levels of maternal T cells, anti-p24, or neutralising antibodies but it was higher, among full-term infants, for those with mothers in the lowest third of the distribution of anti-gp120 levels (53%). On immunoblot, transmitting mothers lacked a gp120 band but not other bands. Protection was not associated with antibody to recombinant peptides from the hypervariable region of the major neutralising gp120 epitope, and the anti-gp120 endpoint dilution titre was similar in transmitting and non-transmitting mothers. Mothers of uninfected full-term infants appear to confer immunological protection against HIV-1 infection of their offspring by way of a high-affinity antibody to a gp120 epitope, whose specificity has importance for vaccine development and possibly perinatal immunotherapy. PMID- 2574303 TI - Selective suprasensitivity to calcitonin-gene-related peptide in the hands in Raynaud's phenomenon. AB - The effects of intravenous infusion of three vasodilators on skin blood flow were studied in eight patients with Raynaud's phenomenon and eight controls, matched for age and sex, by means of the non-invasive technique of laser doppler flowmetry (LDF). The responses to calcitonin-gene-related peptide (CGRP) were compared with those to the endothelium-dependent vasodilator adenosine triphosphate (ATP) and the endothelium-independent vasodilator prostacyclin (epoprostenol; PGI2). In the patients with Raynaud's phenomenon, CGRP induced flushing of the face and hands accompanied by a rise in skin blood flow, whereas in the controls CGRP caused flushing and increased blood flow only in the face. PGI2 caused similar rises in skin blood flow in the hands and face in both groups. ATP did not cause any significant changes in skin blood flow in the face or hands in the patients, but in the controls it increased skin blood flow in the face. Since the suprasensitivity to CGRP of skin blood flow in the hands of patients with Raynaud's phenomenon is not common to other vasodilators, it may reflect a deficiency of endogenous CGRP release in this disorder. PMID- 2574304 TI - Serological effects of Edmonston-Zagreb, Schwarz, and AIK-C measles vaccine strains given at ages 4-5 or 8-10 months. AB - To examine the value of vaccinating children against measles at age 4-5 months three groups of children in Togo were randomly assigned to receive high-dose Edmonston-Zagreb, high-dose Schwarz, or AIK-C vaccines at that age. Two other groups were vaccinated at age 8-10 months, with either the standard Schwarz vaccine or the same batch of AIK-C as for early immunisation. For the 55% of children who were seronegative before vaccination at age 4-5 months seroconversion rates were 96% with the AIK-C, 94% with the Edmonston-Zagreb, and 50% with the high-dose Schwarz. The immune response rates for children who were seropositive before vaccination were estimated to be around 50% with the high dose Edmonston-Zagreb and AIK-C strains and 10% with the Schwarz strain. Seroconversion rates for vaccination at 8-10 months were 87% for the AIK-C and 68% for the Schwarz strains. Thus vaccination with the high-dose Edmonston-Zagreb or the AIK-C strain at 4-5 months was as good as vaccination with the AIK-C strain at 8-10 months and better than vaccination with the standard dose Schwarz strain at 8-10 months. These findings require confirmation by further investigations, particularly epidemiological studies, but they already provide evidence that the administration of AIK-C and high-dose Edmonston-Zagreb strains at 4-5 months is at least as effective as vaccination with the standard strains at 8-10 months. PMID- 2574305 TI - Presymptomatic diagnosis of familial adenomatous polyposis by bridging DNA markers. AB - Familial adenomatous polyposis (FAP) is a disorder with autosomal dominant inheritance, which predisposes to colorectal adenocarcinoma. The gene causing the disorder has been assigned to chromosome 5 by means of a polymorphic DNA marker called C11p11. An informative Dutch pedigree showed that two other linked polymorphic DNA markers, Pi227 and YN5.48, closely flank the FAP locus, one on either side. This finding will allow prenatal and presymptomatic diagnosis of FAP, with more than 99.9% reliability in the majority of families, by means of already available markers. PMID- 2574306 TI - Prenatal sex determination by DNA amplification from maternal peripheral blood. AB - The polymerase chain reaction was used to amplify a Y-specific repeat sequence in peripheral blood DNA samples from 19 pregnant women who had a gestational age of 9 to 41 weeks. Y-specific sequences were amplified from all 12 women who bore a male fetus but in none of 7 women who bore a female fetus. With stringent precautions against contamination, this technique may assist prenatal diagnosis of sex-linked genetic disorders. PMID- 2574307 TI - Political cartography. PMID- 2574308 TI - Lung disease following allogeneic marrow transplantation. PMID- 2574309 TI - Severe symptomless hypertension. PMID- 2574310 TI - Single domain antibodies. PMID- 2574311 TI - Computer-assisted diagnosis. PMID- 2574312 TI - Mass sociogenic illness by proxy: parentally reported epidemic in an elementary school. AB - In a cluster of illness reported among students at an elementary school parents mentioned many signs and symptoms including headache, pallor, dark circles under the eyes, nausea, and vomiting--which they attributed to exposure to recurrent leaks of natural gas at the school. It is likely that the parents spread among themselves the notion of toxic exposure at the school. A questionnaire revealed no spatial clustering, but increased reports of symptoms were related to intense media coverage. A thorough environmental and epidemiological investigation was negative, there being no evidence of a continuing gas leak or other potential causes. At a strictly biological level, the complaints in this reported "cluster" apparently represented the sporadic occurrence of common childhood illnesses. The possibility of an epidemic from toxic exposure at the school caused intense parental concern and led to a major public health problem. The established term "mass sociogenic illness" seems inapplicable here because complaints did not come principally from the students and the apparent epidemic illness was not transmitted among them. The term "mass sociogenic illness by proxy" is proposed to describe this incident, in which transmission in one group (the parents) resulted in reports of an epidemic in another group (students). PMID- 2574313 TI - Familial patterns of narcolepsy. AB - Familial patterns of narcolepsy were investigated in a clinic population of 334 unrelated narcoleptic patients. 40% of probands had at least 1 family member with an isolated daytime sleepiness complaint and 6% had a positive family history of narcolepsy. Multicase families were rare; only two families were found with 3 or more affected relatives. Family members often shared the same HLA-DR2 haplotype as the proband but did not have narcolepsy. However, the risk of disease for first-degree relatives was six to eighteen times greater than that for unrelated individuals. Although most patients were HLA-DR2+, 2 new HLA-DR2- individuals were found. The data predict that as many as 9% of unrelated North-American white patients with narcolepsy will be DR2-. Analysis of these and other data indicates that although strongly associated with disease, the HLA-DR2 haplotype is neither sufficient nor necessary for the development of narcolepsy. PMID- 2574314 TI - Effect of haemodilution on transfusion requirements in liver resection. AB - Between April, 1988, and February, 1989, 22 consecutive patients underwent liver resection (17 hepatectomy, 5 segmentectomy) with intraoperative haemodilution to avoid blood transfusion. The results were compared with those of 22 patients who underwent liver resection without haemodilution between February, 1987, and April, 1988, and who were matched for the nature of the tumour and the type of liver resection. Age, preoperative haematocrit and haemoglobin concentration, and intraoperative blood loss did not differ between the groups who did and did not undergo haemodilution. There was no abnormal bleeding during liver transection in haemodiluted patients. No allogeneic blood products at all were needed in a significantly greater proportion of the group with haemodilution than of the group without (19 [86%] vs 6 [27%]). The two groups also showed significant differences in the total requirements of allogeneic packed red cells (haemodilution 9 units, no haemodilution 84 units) and fresh frozen plasma (9 vs 119 units). Although the haematocrit was slightly but significantly lower in the group who underwent haemodilution than in those who did not on postoperative days 1 and 8, the differences had disappeared by the second postoperative month. Postoperative complication rates, abnormal results in liver biochemical tests, and lengths of hospital stay were the same in patients with and without haemodilution. Intraoperative haemodilution in patients undergoing liver resection reduced requirements for all blood products, further lowering the risks associated with liver resection. PMID- 2574315 TI - A systems analyst asks about AIDS research funding. PMID- 2574316 TI - United States. AIDS in teenagers. PMID- 2574317 TI - Endometrial resection and fluid absorption. PMID- 2574318 TI - Female sterilisation. PMID- 2574319 TI - Potential protection by cyclosporin against glucocorticoid effects on bone. PMID- 2574320 TI - Sudden infant death and glycogen storage disease. PMID- 2574321 TI - Cot death and sleeping position. PMID- 2574322 TI - Scavenging free radicals to prevent stress-induced gastric mucosal injury. PMID- 2574323 TI - Hepatitis C virus: a possible cause of chronic hepatitis in alcoholics. PMID- 2574324 TI - Human herpesvirus 6 harbouring in kidney. PMID- 2574325 TI - Ovulation induction and neural tube defects. PMID- 2574326 TI - Extrapyramidal signs in dementia of Alzheimer type. PMID- 2574327 TI - Aminoacid isomerisation and microwave exposure. PMID- 2574328 TI - Recurrent melanoma after topical tretinoin. PMID- 2574329 TI - Cyclosporin for dystrophic epidermolysis bullosa. PMID- 2574330 TI - Family outbreak of Blastocystis hominis associated gastroenteritis. PMID- 2574331 TI - Psoriasis and the doctor fish. PMID- 2574332 TI - Staphylococcus lugdunensis peritonitis. PMID- 2574333 TI - Chloroquine-resistant Plasmodium vivax. PMID- 2574334 TI - What do travellers know about malaria? PMID- 2574335 TI - Mumps vaccine complications: which strain? PMID- 2574336 TI - Leishmaniasis masking tuberculosis. PMID- 2574337 TI - Assessment of workload in neonatal medicine. PMID- 2574338 TI - Deep-vein thrombosis and pulmonary tuberculosis. PMID- 2574339 TI - Iatrogenic post-traumatic stress disorder. PMID- 2574340 TI - Spontaneous rupture of spleen following streptokinase therapy. PMID- 2574341 TI - Transient impairment of renal function after streptokinase therapy. PMID- 2574342 TI - Efficacy and safety of oral iron chelator L1 in anaemic rheumatoid arthritis patients. PMID- 2574343 TI - Gallbladder contraction and type of fat. PMID- 2574344 TI - Compassionate release of anti-HIV drugs. PMID- 2574345 TI - Clinical trials of zidovudine in HIV infection. PMID- 2574346 TI - Gangrenous stomatitis in a child with AIDS. PMID- 2574347 TI - Coats' type retinitis pigmentosa and subretinal neovascularisation in a patient with renal failure. PMID- 2574348 TI - Pneumocystis prophylaxis: which drug, what dose? PMID- 2574349 TI - Benzodiazepine withdrawal. PMID- 2574350 TI - Raised plasma endothelin in aneurysmal subarachnoid haemorrhage. PMID- 2574351 TI - Evidence of gastritis with several Helicobacter pylori strains. PMID- 2574352 TI - Omeprazole, Helicobacter pylori, gastritis, and duodenal ulcer. PMID- 2574353 TI - Peroperative endoscopy in Peutz-Jeghers syndrome. PMID- 2574354 TI - Screening for cystic fibrosis. PMID- 2574356 TI - Frequency of delta F508 mutation on cystic fibrosis chromosomes in UK. PMID- 2574355 TI - Delta F508 gene deletion in cystic fibrosis in southern Europe. PMID- 2574357 TI - First-trimester diagnosis of Wiskott-Aldrich syndrome by DNA markers. PMID- 2574358 TI - Effect of GM-CSF on circulating granulocyte-monocyte progenitors in autologous bone marrow transplantation. PMID- 2574359 TI - Jehovah's Witness transfused without consent: a Canadian case. PMID- 2574360 TI - Restriction of dietary protein and progression of renal failure in diabetic nephropathy. AB - In a study of the effect of a low-protein diet on the progression of renal disease 19 insulin-dependent diabetic patients with persistent clinical proteinuria were observed for 12-39 (mean 29) months while they were on a normal protein diet (1.13 [0.06] g/kg per day), then for 12-49 (mean 33) months on a low protein diet (0.67 [0.03] g/kg per day). The low-protein diet had no adverse effect on nutrition or glycosylated haemoglobin concentration. Mean supine blood pressure (BP) fell slightly on the low-protein diet and was probably due to the start or modification of antihypertensive medication in 9 patients. The mean rate of decline in glomerular filtration rate fell from 0.61 (SEM 0.14) ml/min per month with the normal-protein diet to 0.14 (0.08) with the low-protein diet, and this effect remained highly significant after adjustment for blood pressure, energy intake, and glycosylated haemoglobin. The rise in the fractional clearance of albumin during a normal-protein diet stopped with the low-protein diet, and there was a significant fall in albumin excretion from 467 (95% CI 234-895) micrograms/24 h on the normal-protein to 340 (138-719) on the low-protein diet. Thus, a low-protein diet, with its reduction in protein and possibly other dietary components such as phosphate or fat, seems to retard the rate of decline of glomerular filtration rate in diabetic nephropathy independently of blood pressure changes and glycaemic control. PMID- 2574361 TI - Relation between Escherichia coli R(rough)-forms in gut, lipid A in liver, and primary biliary cirrhosis. AB - Since antimitochondrial antibodies (AMA) specific to primary biliary cirrhosis (PBC) recognise enterobacterial proteins and can be induced by R(rough)-mutants of enterobacteriaceae a study was done to find out the prevalence of enterobacterial R-forms in stool samples of patients with chronic inflammatory liver diseases. Liver biopsy specimens were also examined for lipid A, a common antigenic component of the cell wall in gram-negative bacteria. In all stool samples from the 21 patients with PBC Escherichia coli R-forms constituted up to half of the total amount of E coli. In contrast E coli R-forms were detectable in the stools of only 1 healthy control (n = 20), and in 25% of patients with other cholestatic diseases (n = 10), chronic hepatitis type B (n = 15), type non-A, non B hepatitis (n = 15), or chronic pancreatitis and fat malabsorption (n = 8). An immunoblot technique showed that E coli R-forms isolated from patients' stools contained PBC-specific AMA-reactive proteins with molecular weights of 70-80 kD and 50 kD. Deposits of lipid A, located primarily in the cytoplasm of hepatocytes, were found in 11 patients with PBC but not in the liver of patients with chronic viral hepatitis. Circulating antibodies against lipid A were found rarely and in low titres. The data support the hypothesis that intestinal enterobacterial R-forms are aetiologically important in PBC and that antigens released from the bacterial cell wall contribute to the pathogenesis of the disease. PMID- 2574362 TI - Liver disease and bile duct abnormalities in adults with cystic fibrosis. AB - A quarter of adults with cystic fibrosis, 57 of 233, had abnormal liver function. Patients with hepatic dysfunction were further investigated by ultrasound, hepatobiliary scintigraphy, and endoscopic retrograde cholangiography (ERC). 17 of the 23 patients studied had abnormalities on imaging. All 15 patients who underwent ERC had abnormal intrahepatic ducts, but only 2 had stricture of the common bile duct. These findings suggest that, in patients with cystic fibrosis, intrahepatic impairment of biliary drainage may be important in the pathogenesis of liver disease. PMID- 2574363 TI - In-utero transplantation of fetal liver haemopoietic stem cells in monkeys. AB - To evaluate the potential of in-utero transplantation of fetal haemopoietic stem cells (HSCs) for permanent engraftment as a treatment of congenital haemoglobinopathies, fetal rhesus monkeys were transplanted with HSCs derived from fetal livers. Five pregnant monkeys (60-62 days' gestation) were given an in utero intraperitoneal injection of fetal liver cells (10(8)-10(9) cells/kg estimated fetal recipient body weight) derived from opposite sex donors at 59-68 days' gestation. Engraftment was confirmed by karyotype analysis of peripheral blood leucocytes and bone marrow; cells of donor sex were found among the recipient cells. Donor cell engraftment was apparent in four of five in-utero HSC transplant recipients at birth. Engraftment involved lymphoid (2.9-8.0% donor cells), erythroid (5.3-12.5%), and myeloid (8.5-15.4%) lineages and has persisted for up to 2 years without evidence of graft-versus-host disease. PMID- 2574364 TI - Conservative management of perforated peptic ulcer. PMID- 2574365 TI - Clozapine. PMID- 2574366 TI - Balloon dilatation of the prostate. PMID- 2574367 TI - Association between serum albumin and mortality from cardiovascular disease, cancer, and other causes. AB - In a prospective study of 7735 middle-aged British men (British Regional Heart Study) 660 died during an average follow-up period of 9.2 years. There was a marked increase in mortality rate with decreasing serum albumin concentrations that persisted even after adjustment for age, social class, town of residence, cigarette smoking, serum total cholesterol, systolic blood pressure, serum total calcium, and forced expiratory volume in 1 s. When serum albumin concentration was less than 40 g/l, the mortality rate was 23/1000 per year compared with 4/1000 per year for a concentration equal to or above 48 g/l. A similar pattern was observed for cardiovascular, cancer, and other deaths. The associations persisted for cardiovascular disease and cancer even when deaths within the first five years of follow-up were excluded. These results must be interpreted with caution since there was no prior hypothesis concerning serum albumin. However, the strength of the association between serum albumin and mortality seems to be comparable with that for cigarette smoking. PMID- 2574368 TI - Clinical significance of Candida isolated from peritoneum in surgical patients. AB - Over a 2-year period, all surgical patients from whom Candida was isolated from intra-abdominal specimens were evaluated. All but 1 of the 49 evaluable patients had either a spontaneous perforation (57%) or a surgical opening of the gastrointestinal tract (41%). Candida caused infection in 19 patients (39%), of whom 7 had an intra-abdominal abscess and 12 peritonitis. In the other 30 patients (61%), there were no signs of infection and specific surgical or medical treatment was not required. Candida was more likely to cause infection when isolated in patients having surgery for acute pancreatitis than in those with either gastrointestinal perforations or other surgical conditions. The development of a clinical infection was significantly associated with a high initial or increasing amount of Candida in the semiquantitative culture. Surgery alone failed in 16 of 19 patients (84%), of whom 7 died and 9 recovered after combined antifungal and surgical treatment. The overall mortality and the mortality related to infections were significantly higher in the patients with intraabdominal candidal infections than in those without such infections. PMID- 2574369 TI - Bias against the null hypothesis: the reproductive hazards of cocaine. AB - To examine whether studies showing no adverse effects of cocaine in pregnancy have a different likelihood of being accepted for presentation by a large scientific meeting, all abstracts submitted to the Society of Pediatric Research between 1980 and 1989 were analysed. There were 58 abstracts on fetal outcome after gestational exposure to cocaine. Of the 9 negative abstracts (showing no adverse effect) only 1 (11%) was accepted, whereas 28 of the 49 positive abstracts were accepted (57%). This difference was significant. Negative studies tended to verify cocaine use more often and to have more cocaine and control cases. Of the 8 rejected negative studies and the 21 rejected positive studies, significantly more negative studies verified cocaine use, and predominantly reported cocaine use rather than use of other drugs. This bias against the null hypothesis may lead to distorted estimation of the teratogenic risk of cocaine and thus cause women to terminate their pregnancy unjustifiably. PMID- 2574370 TI - Antenatal testing for human immunodeficiency virus. Results from the Royal College of Obstetricians and Gynaecologists' National Study of HIV Infection in Pregnancy. AB - Current policies on antenatal testing for human immunodeficiency virus (HIV) in the main obstetric units of the United Kingdom and the Republic of Ireland were surveyed by postal questionnaire; 294 of 299 units responded. HIV testing was available at 192 (65%) of the 294 units that responded. 414 HIV-positive pregnancies in 386 women were reported from 74 (25%) units. Most were from Scotland, the four Thames Regions, and Ireland. In 46% of the HIV-positive women the infection was identified by antenatal testing; the remainder had been tested previously and knew that they were infected. The findings support the view that selective antenatal testing should be established in areas where no testing is offered at present and possibly that testing should be offered to all pregnant women in high-prevalence areas. PMID- 2574371 TI - Psychological support for cancer patients. PMID- 2574372 TI - Benefits of in-vitro fertilisation. PMID- 2574373 TI - Lymphopenia after snakebite. PMID- 2574374 TI - Subtelomeric breakage and chromosome exchange. PMID- 2574375 TI - Fish and the heart. PMID- 2574376 TI - Gravity, blood pressure, and bleeding time. PMID- 2574377 TI - Near-death experience. PMID- 2574378 TI - Prenatal diagnosis of junctional epidermolysis bullosa. PMID- 2574379 TI - Cirrhosis of the liver and mouldy bread. PMID- 2574380 TI - Extrapulmonary pneumocystosis in patients taking aerosolised pentamidine. PMID- 2574381 TI - Acute rhabdomyolysis coincident with primary HIV-1 infection. PMID- 2574382 TI - Airway obstruction during sleep in children. PMID- 2574384 TI - Safety of amoxapine. PMID- 2574383 TI - Multiple drug reactions in a patient with AIDS. PMID- 2574385 TI - Computer networks in medicine. PMID- 2574386 TI - Privatisation of care in China. PMID- 2574387 TI - Community treatment orders for mental illness. PMID- 2574388 TI - Clinical relevance of specific IgG antibodies of cardiolipin. PMID- 2574389 TI - High-dose buspirone in case of tardive dyskinesia. PMID- 2574390 TI - Schizophrenia and chromosomes. PMID- 2574392 TI - Improved survival with surgical treatment of both primary lung cancer and brain metastases. PMID- 2574391 TI - Pathogenesis of Crohn's disease. PMID- 2574393 TI - Lithium monitoring close to the patient. PMID- 2574395 TI - Fissures in coronary atherosclerotic plaques. PMID- 2574394 TI - Rhabdomyolysis and acute tubular necrosis in coniine (hemlock) poisoning. PMID- 2574396 TI - Hepatitis due to human herpesvirus-6. PMID- 2574397 TI - Increase in admissions for Neisseria meningitidis infection in Australia. PMID- 2574398 TI - Spontaneous pneumothorax. PMID- 2574399 TI - Confidentiality and the dangerous psychiatric patient. PMID- 2574400 TI - Sick child left in the charge of unsupervised students. PMID- 2574401 TI - L-tyrosine induces synthesis of melanogenesis related proteins. AB - In cultured amelanotic hamster melanoma cells L-tyrosine induces melanogenesis. This induction involves an increase in intracellular concentration of proteins precipitated by polyclonal anti-tyrosinase antibodies, and stimulation of the Vmax of tyrosinase activity. Therefore it is suggested that in hamster melanoma cells L-tyrosine induces synthesis of tyrosinase and melanogenesis related proteins. PMID- 2574402 TI - The ontogeny and localization of glutamine synthetase gene expression in rat brain. AB - A 2.4 kb cDNA clone containing the coding sequence for glutamine synthetase (GS) was isolated from a rat brain cDNA library, and a probe constructed from this cDNA was utilized in Northern analysis of total RNA to study the tissue distribution and the ontogeny of GS mRNA expression in the rat brain from embryonic day 14 (E14) to adulthood. The levels of GS mRNA were highest in the brain, followed by kidney and liver. In the brain, the GS message was detected as early as E14, earlier than it can be detected by either enzymatic assays of GS activity or by immunocytochemical localization of GS. The relatively low levels of GS mRNA seen at E14 increase to a peak around the time of birth, and in the second postnatal week another rise in GS message occurs approaching adult levels by P15. Localization of GS to astrocytes in the brain was confirmed using both immunocytochemistry and in situ hybridization. PMID- 2574403 TI - In situ hybridization analysis of the somatostatin-containing neuron system in developing cerebellum of rats. AB - We used in situ hybridization histochemistry to examine the postnatal development of the somatostatin (SRIF) synthesizing system in the cerebellum of rats. There are numerous hybridizing neurons from 1 to 9 days after birth. These occur throughout the cerebellum including the developing medulla and cortex except in the external granular cell layer. The lateral cerebellar nucleus also contains SRIF gene-containing cells. The intensity of the signals for SRIF mRNA in the cerebellum decreases with age. There is a drastic decrease in SRIF mRNA in the lateral cerebellar nucleus. SRIF cells cannot be detected in the lateral cerebellar nucleus of adult rats, whereas a small, yet significant number of SRIF cells are scattered in the cerebellar medulla. However, the cerebellum of adult rats still contains a significant number of labeled cells in the granular cell layer, although the intensity for SRIF mRNA decreases from 14 days after birth to adulthood. SRIF gene-expressing cells in the cerebellar cortex are located primarily in the granular cell layer and appear to correspond to Golgi cells judging from their characteristic features. These results are consistent with our previous immunohistochemical study on the decrease of SRIF immunoreactivity in the cerebellum of adult rats. These findings, together with a recent study of transient SRIF receptor-expressing cells in the developing cerebellum suggest that SRIF acts during cerebellar development. PMID- 2574404 TI - Hormonal control of the development and regulation of tyrosine hydroxylase expression within a sexually dimorphic population of dopaminergic cells in the hypothalamus. AB - In situ hybridization histochemistry was used to examine the development and regulation of tyrosine hydroxylase (TH) mRNA within the sexually dimorphic population of dopaminergic cells in the anteroventral periventricular nucleus (AVPv) of the hypothalamus. The AVPv contains over 3 times as many TH mRNA containing cells in female rats, compared with males. This sexual dimorphism appears to be dependent on perinatal levels of gonadal steroids since orchidectomy of newborn males increased, and treatment of newborn females with testosterone decreased, the number of TH mRNA-containing cells detected within the AVPv. In addition, circulating gonadal steroids appear to downregulate TH expression within these cells in both adult male and female rats. In adult male animals, gonadectomy increased the number of TH mRNA cells in the AVPv within 7 days. Similarly, estradiol treatment prevented the increase in the number of TH mRNA-containing cells within the AVPv seen in ovariectomized female rats. No sexual differences were detected in the number of TH mRNA-containing cells within the suprachiasmatic preoptic nucleus, located just ventral to the AVPv. These findings indicate that perinatal gonadal steroids influence the number of cells within the AVPv that express TH in detectable amounts by determining the number of cells that are capable of producing sufficient quantities of TH message, as opposed to sex-specific alterations in the post-translational mechanisms. In the adult, circulating gonadal steroids appear to downregulate TH expression within these cells suggesting that testosterone and/or estrogen may exert a sustained influence on the biosynthetic activity of this sexually dimorphic population of dopaminergic cells. PMID- 2574405 TI - Stimulation of pituitary hormone secretion by neurotransmitter amino acids in humans. AB - The effects of several neurotransmitter amino acids on pituitary hormone secretion were examined in normal humans. Oral administration of 10 g of glutamic acid stimulated the secretion of prolactin (PRL) and cortisol to approximately twice baseline values, with no effect on GH, TSH or LH. Aspartic acid (10 g), taurine (5 g), and cysteine (5 or 10 g) had no consistent effect on any hormone measured, although the lack of effect of aspartic acid may relate to the modest increments in serum concentration achieved. Glutamic acid may be an important modulator of PRL and ACTH secretion in humans. PMID- 2574407 TI - Cooperation between humoral factor(s) and Lyt-2+ T cells in effective clearance of Sendai virus from infected mouse lungs. AB - The mechanism of cooperation between the L3T4+ and Lyt-2+ T cell subsets in effective clearance of Sendai virus from infected mouse lungs was studied by adoptive cell transfer using nude mice. Simultaneous transfer of a long-term cultured Sendai virus-specific L3T4+ T cell line with L3T4+ cell-depleted immune spleen cell (L3T4-) fraction to infected nude mice could result in viral clearance, although single injection with either of these cells was not effective. Instead of the L3T4+ T cells, culture supernatants of the L3T4- T cell line or concanavalin A-stimulated mouse spleen cells and mouse serum immunized with the virus were also active in the cooperative viral clearance with L3T4- fraction. The role of the Sendai virus-sensitized L3T4- cell fraction in cooperative viral clearance with humoral factors could be replaced by neither T cell-deprived immune spleen cell fraction nor normal spleen cells. The 1,500 units of recombinant mouse interleukin 2 (IL-2), which was more than 12 times the IL-2 activity present in the supernatants of the T cell line or concanavalin A stimulated spleen cells, failed to clear the virus in combination with the L3T4- fraction. Monoclonal antibodies to Sendai or mouse hepatitis viruses were also effective in the cooperative antiviral activity. IL-2 activity was not detected in these monoclonal antibodies and the mouse immune serum. Single injection of any humoral factors failed to clear the virus. These results indicate that Sendai virus-sensitized Lyt-2+ subset of T cells acts cooperatively with humoral factor(s) other than IL-2 or Sendai virus-specific antibody present in supernatants of the T cell line, of concanavalin A-stimulated spleen cells or hybridomas, and in mouse serum immunized with the virus. PMID- 2574406 TI - Central nervous system control of glycogenolysis and gluconeogenesis in fed and fasted rat liver. AB - The influence of brain cholinergic activation on hepatic glycogenolysis and gluconeogenesis was studied in fed and 48-hour fasted rats. Neostigmine was injected into the third cerebral ventricle and hepatic venous plasma glucose, glucagon, insulin, and epinephrine were measured. The activity of hepatic phosphorylase-a and phosphoenolpyruvate-carboxykinase (PEP-CK) was also measured. Experimental groups: 1, intact rats; 2, rats infused with somatostatin through the femoral vein; 3, bilateral adrenodemedullated (ADMX) rats; 4, somatostatin infused ADMX rats; 5, 5-methoxyindole-2-carboxylic acid (MICA) was injected intraperitoneally 30 minutes before injection of neostigmine into the third cerebral ventricle of intact rats. MICA treatment completely suppressed the increase in hepatic glucose in fasted rats, but had no effect in fed rats. Phosphorylase-a activity was not changed in fasted rats, but increased in fed rats, intact rats, somatostatin-infused rats, somatostatin-infused ADMX rats, and ADMX rats in that order. PEP-CK was not changed in fed rats, but increased at 60 and 120 minutes after neostigmine injection into the third cerebral ventricle in fasted rats. We conclude that, in fed states, brain cholinergic activation causes glycogenolysis by epinephrine, glucagon, and direct neural innervation. In fasted states, on the other hand, gluconeogenesis is dependent on epinephrine alone to increase hepatic glucose output. PMID- 2574408 TI - Cold packs: effective topical analgesia in the treatment of painful stings by Physalia and other jellyfish. AB - A study has shown that, when applied to Physalia ("bluebottle") jellyfish stings, cold packs are effective as topical analgesia in the relief of mild-to-moderate skin pain. The application of ice also has been shown to be effective for topical analgesia in a number of other jellyfish stings, including by Cyanea ("hair jellyfish"), Tamoya sp. ("Moreton Bay stinger" or "fire jelly") and Carybdea rastoni ("jimble") as well as by Physalia. In the current state of knowledge, cold packs or ice are recommended as the first-aid treatment for jellyfish stings with local skin pain. PMID- 2574409 TI - The new and newer antianxiety agents. AB - Anxiolytic drugs are adjuncts to non-pharmacological treatments for anxiety. Alcohol and tobacco remain the major psychoactive agents that are used in our community. Benzodiazepine drugs are the agents of choice if an acute reduction in anxiety or intermittent therapy is needed and are helpful for long-term use in a few patients. For panic disorders, alprazolam is effective for short- and long term treatment, although it needs a slow reduction in dosage and carries a risk of withdrawal reactions in about 30% of sufferers. Clonazepam also may help panic attacks and possibly other benzodiazepine agents would show similar effects at equivalent doses. Antidepressant drugs, including monoamine-oxidase inhibitor agents, although more toxic and sometimes less tolerated than is alprazolam, have antipanic effects in high doses and are of use for prolonged therapy for panic disorders. Neuroleptic agents' general usefulness as anxiolytic drugs is restricted because of their acute and long-term toxicity. There is no place for the use of antidepressant or neuroleptic drugs as treatments of first choice in uncomplicated generalized anxiety. beta-blocking agents have limited adjunctive use for performance anxiety and social phobias. Buspirone heralds a new class of anxiolytic agents. Buspirone has advantages in patients who can tolerate its slow onset of action, with reduced psychomotor effects, lower interactive effects with cortical depressant substances and a seeming lack of dependency or any withdrawal syndrome. PMID- 2574411 TI - When the snake expert is bitten. PMID- 2574410 TI - Successful use of Chironex antivenom by members of the Queensland Ambulance Transport Brigade. AB - We report the first administration in Australia by ambulance officers of the Commonwealth Serum Laboratories' Chironex fleckeri antivenom, in two separate, major, potentially life-threatening Chironex envenomations. In both cases, the antivenom was effective in helping to relieve signs and symptoms (including pain). This antivenom still is the most specific part of the treatment of a major Chironex fleckeri sting after stabilization of the airway, breathing and circulation. The additional use of verapamil may contribute to the prevention of some of the cardiac complications that result from the direct effects of the Chironex venom. PMID- 2574412 TI - Treatment of schizophrenia. PMID- 2574413 TI - Bronchial hyperresponsiveness in cardiac failure. PMID- 2574414 TI - Abuse liability of anxiolytics and sedative/hypnotics: methods assessing the likelihood of abuse. PMID- 2574415 TI - Analysis of fusion gene and encoded photopigment of colour-blind humans. AB - In humans, long-wavelength-sensitive and middle-wavelength-sensitive cone pigments are encoded by genes lying in a head-to-tail tandem array on the X chromosome. Deficiencies in red-green colour vision seem to arise from unequal recombination of these normal X-linked genes. In some dichromats this recombination is believed to yield a fusion gene encoding a product with an absorption spectrum similar to that of one or the other of the normal photopigments. Until now, however, such a relationship between the structure of a pigment gene and the spectral properties of its encoded pigment has not been directly shown. We have now sequenced a fusion gene isolated from a red-green colour-blind human and determined the spectral properties of the pigment that it encodes. The absorption spectrum of the photopigment was very similar to that of normal middle-wavelength-sensitive photopigment, even though about half of its DNA coding sequence seems to be derived from a gene encoding normal long wavelength-sensitive pigment. These results indicate the regions of the X-encoded photopigment apoproteins that are responsible for differences in their spectral tuning, and imply that the striking variations in colour vision among anomalous trichromats of a particular type are not attributable to anomalous pigments with differing spectral peaks. PMID- 2574417 TI - [Frequency and surgical mortality in surgery of the heart and of the intrathoracic large vessels. I. Direct coronary revascularizations]. AB - The number of bypass operations has increased considerably in the last decade. This applies mainly to the multiple bypasses. The number of single bypasses is beginning to decrease. The proportion of the elderly among the patients is rising markedly. The surgical mortality is decreasing strongly, especially among males. It is higher for females than for males. Interestingly, this mortality is not higher for multiple bypasses than for single ones, rather the reverse. The mortality rate of implantation of the internal mammary artery into a coronary vessel is very low. The surgical mortality of bypass operations is lower than, for instance, that of partial gastrectomy or of pulmonary lobectomy. PMID- 2574416 TI - Dissection of functional domains of the pituitary-specific transcription factor GHF-1. AB - The specific expression of growth hormone (GH) in the somatotrophic cells of the anterior pituitary is largely attributable to a short promoter in the 5' flanking region of the GH gene. This promoter contains two binding sites for the transcription factor GHF-1, the expression of which is also specific to cells of the somatotrophic lineage and correlates with activation of the GH gene in the developing mouse pituitary. Various studies indicate that GHF-1 is the main determinant of cell type-specific expression of the GH gene. GHF-1 is a member of the POU-domain class of proteins that each contain two highly conserved sequence motifs, the homoeodomain and the POU-specific domain. Here we report that the GHF 1 homoeodomain is sufficient for sequence-specific DNA binding, although its activity is stimulated by the POU-specific domain, which does not interact directly with the DNA. Transcriptional activation is mediated by a separate domain rich in hydroxylated amino-acid residues. Similar sequences are present in other cell type-specific transcription factors. PMID- 2574418 TI - Release of [3H]L-glutamate and [3H]L-glutamine in rat cerebellum slices: a comparison of the effect of veratridine and electrical stimulation. AB - Depolarization-elicited release of neurotransmitter glutamate was studied in rat cerebellar slices previously loaded with either [3H]L-glutamate or [3H]L glutamine. Both depolarization conditions used (e.g. long-lasting tonic depolarization elicited by veratridine, or short repetitive electrical pulses) increased 6 to 8 folds the release of labelled glutamate and of another compound, presumably alpha-ketoglutarate, without modifying the release of labeled glutamine. Because of the position of the label in the precursor radioactive molecules, GABA was weakly labeled and aspartate was unlabeled. The properties of the evoked glutamate release from cerebellar slices were those of a neurotransmitter since it was inhibited by tetrodotoxin and was Ca2+-dependent. Alpha-ketoglutarate is either coreleased from nerve terminals or is released from astrocytes and could participate in glutamate recycling. The data confirm the generally accepted model implying the presence of two neurotransmitter glutamate pools, a neuronal pool of newly synthesized glutamate and an astrocytic storage pool, but in addition indicate that the former is in rapid isotopic equilibrium with the extracellular compartment. Our present results also indicate that the glutamate/glutamine cycle is not activated in depolarizing conditions. PMID- 2574419 TI - Different long-term effects of bilateral and unilateral nucleus basalis lesions on rat cerebral cortical neurotransmitter content. AB - Young adult rats received either unilateral or bilateral ibotenic acid infusions in their nucleus basalis, destroying most of the cholinesterase-staining neurons in that region. Cerebral cortex levels of choline acetyltransferase, somatostatin, neuropeptide Y, and monoamines were then assayed 2.5 and 10 months after bilateral lesions, or, 2.5, 10, and 14 months after unilateral lesions. Entorhinal and cerebral cortex levels of several amino acid transmitters were also measured. As expected, choline acetyltransferase activity was decreased in the frontal cortex ipsilateral to the ibotenic acid infusion in unilaterally or bilaterally lesioned animals. Parietal cortex concentrations of somatostatin and neuropeptide Y were altered by lesioning in a complicated, time-dependent manner. Thus, while unilateral lesions transiently decreased or had no effect on these neuropeptide levels, bilateral lesions elevated the level of each neuropeptide by over 100% at 10 months. Other cortical transmitter systems investigated appeared to be less affected by nucleus basalis-lesions. Unilateral lesions had no effect on prefrontal cortex norepinephrine, serotonin, or dopamine content at 14 months post-lesioning. These different neurochemical effects of unilateral and bilateral nucleus basalis lesions may be important for developing a model for the trans synaptic effects of cortical cholinergic deafferentation. PMID- 2574420 TI - Penicillin-induced convulsions have preferential effects on transmitter glutamate pools in rat neostriatum. AB - Convulsant doses of penicillin and elevated ambient pressure of 41 bar enhance the excitability of neurons. Their effects have been studied in neostriatal tissue with methods allowing differentiation between transmitter and metabolic glutamate pools. Levels of glutamate (Glu), glutamine (Gln), aspartate (Asp); gamma-aminobutyric acid and taurine were measured in the intact and decorticated neostriatum and parieto-occipital cortex of rats with a unilateral frontal cortex ablation. Intravenous infusion of penicillin at 1 bar decreased the neostriatal Glu content in the intact but not in the decorticated hemisphere. Pressure of 41 bar significantly decreased the level of Asp in the decorticated side only. Infusion of penicillin at 41 bar reduced the levels of Glu by 20.1% and Gln by 21.0% in the intact neostriatum only, whereas it decreased the Asp level in both sides as compared to control. The cortical Glu content was decreased only after infusion of penicillin at 41 bar. The results suggest that intravenous penicillin has a more pronounced effect on transmitter than on metabolic Glu pools in rat brain. PMID- 2574422 TI - Evidence for evoked release of adenosine and glutamate from cultured cerebellar granule cells. AB - Evoked release of [3H]-D-aspartate which labels the neurotransmitter glutamate pool in cultured cerebellar granule cells was compared with evoked release of adenosine from similar cultures. It was found that both adenosine and [3H]-D aspartate could be released from the neurons in a calcium dependent manner after depolarization of the cells with either 10-100 microM glutamate or 50 mM KCl. Cultures of cerebellar granule cells treated with 50 microM kainate to eliminate GABAergic neurons behaved in the same way. This together with the observation that cultured astrocytes did not exhibit a calcium dependent, potassium stimulated adenosine release strongly suggest that cerebellar granule cells release adenosine in a neurotransmitter-like fashion together with glutamate which is the classical neurotransmitter of these neurons. Studies of the metabolism of adenosine showed that in the granule cells adenosine is rapidly metabolized to ATP, ADP, and AMP, but in spite of this, adenosine was found to be released preferential to ATP. PMID- 2574421 TI - Co-existence between receptors, carriers, and second messengers on astrocytes grown in primary cultures. AB - This overview deals with the current important problem of the expression by astrocytes of a set of functional and neurochemical properties which, until a few years ago, were thought to be specific for neurons. The interaction of different receptor functions and carrier systems in astrocytes and the functional importance of second messenger systems is discussed. PMID- 2574423 TI - Regional changes in the concentrations of glutamate, glycine, taurine, and GABA in the vitamin B-6 deficient developing rat brain: association with neonatal seizures. AB - It is well known that a dietary restriction of vitamin B-6 during gestation and lactation produces spontaneous seizures in neonatal animals. Since pyridoxal phosphate, one of the biologically active forms of vitamin B-6, is the cofactor for GAD the neonatal seizures have been attributed to low levels of brain GABA as a result of cofactor depletion. Although GABA levels are significantly lower in B 6 restricted neonatal rats with spontaneous seizures, seizure activity is not present in B-6 deficient adult rats or 28 day old rats in the present study, despite significantly low levels of brain GABA. These facts suggest that depletion of GABA is not the only biochemical alteration essential for the emergence of seizures. In the present study, the effect of vitamin B-6 undernutrition on the concentrations of the neuroactive amino acids, Glu, Gly, Tau, and GABA was determined in selected regions of the developing rat brain. The results show that the concentrations of Glu, Tau, and GABA were significantly lower and GLY significantly higher in selected brain regions of the B-6 restricted 14 day old rat compared to control tissue. Most of these changes were unique to 14 days of age, the time when spontaneous seizures are observed, and not present at 28 or 56 days of age when seizures are absent. This pattern of amino acid changes in the brain and the magnitude of the changes was consistent with those measured in a variety of chemically-induced animal models of epilepsy and in human epileptic foci.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574425 TI - Excitatory amino acid blockers differentially affect bursting of in vitro hippocampal neurons in two pharmacological models of epilepsy. AB - The role of excitatory amino acid neurotransmitters in generating two distinct types of epileptiform discharge in the CA3 region of hippocampal slices was examined in the guinea-pig using a variety of different excitatory amino acid blockers. In magnesium-free medium the N-methyl-D-aspartate receptor antagonist, DL-aminophosphonovaleric acid, and the putative N-methyl-D-aspartate channel blockers phencyclidine and ketamine, reduced the amplitude and duration of spontaneous bursts and blocked their afterdischarges. In marked contrast none of these compounds significantly depressed spontaneous bursts recorded in the presence of 2 mM Mg2+ and penicillin. This was confirmed for individual slices where Mg2+-free bursts had previously been suppressed by the same concentration of blocker. Therefore, the N-methyl-D-aspartate receptor mechanism does not contribute significantly to the generation of this type of epileptiform discharge. The channel blockers lost their effect on Mg2+-free bursts in the presence of penicillin; however, the receptor blockers did not. This is probably due to the unique mechanisms of action of the channel blockers. This implies that different types of N-methyl-D-aspartate blockers might be effective anticonvulsants only in specific conditions. While the non-specific excitatory amino acid blocker, kynurenic acid, was effective against both burst types it appeared to suppress them by different mechanisms. Kynurenic acid depressed the amplitude and duration of Mg2+-free bursts but its only effect on penicillin bursts was to reduce their frequency. This suggests that neither N-methyl-D aspartate nor non-N-methyl-D-aspartate receptors play a major role in the production of the paroxysmal depolarizing shift resulting from the block of GABA mediated inhibition by penicillin. However, these receptors may be involved in generating the spontaneous activity which triggers the bursts. PMID- 2574424 TI - Desenkephalin-gamma-endorphin is an antagonist of the hyperactivity response induced by infusion of dopamine into the nucleus accumbens of rat and ventral striatum of marmoset. AB - The ability of desenkephalin-gamma-endorphin (DE gamma E; ORG5878) to antagonise a raised limbic dopamine function was investigated in the rat and common marmoset. Dopamine was infused for 13 days directly into the nucleus accumbens of the rat and ventral striatum of the marmoset and increased locomotor activity. Such increases in both the rat and marmoset were antagonised by the subcutaneous injection of DE gamma E, administered in a range 10-500 micrograms/kg (t.i.d.), during the 13 day period of infusion of dopamine. Treatment with dopamine alone or in combination with DE gamma E failed to influence the level of spontaneous locomotor activity after discontinuing treatment. In contrast, in experiments performed in the rat, the level of spontaneous locomotor activity was increased 2 to 3-fold after cessation of a regimen of infusion of dopamine and haloperidol. The increases in activity were antagonised by DE gamma E (50 and 100 micrograms/kg t.i.d., s.c., for 2 days). In additional experiments in the marmoset, using animals initially selected as "high activity" responders to challenge with (-)N-n-propylnorapomorphine, the infusion of dopamine caused a reversal in responsiveness to the stimulant effects of (-)N-n propylnorapomorphine on locomotor activity some 2-4 weeks after discontinuing the infusion of dopamine. The administration of fluphenazine (0.01-2.5 mg/kg b.d.), during the infusion of dopamine, failed to prevent the subsequent change in responsiveness to (-)N-n-propylnorapomorphine, whereas a regimen of dopamine and DE gamma-E (25-100 micrograms/kg t.i.d.) prevented such changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574426 TI - Quantitative immunogold analysis reveals high glutamate levels in retinal and cortical synaptic terminals in the lateral geniculate nucleus of the macaque. AB - An immunogold procedure has been used on ultrathin sections of the parvo- and magnocellular layers of the dorsal lateral geniculate of the rhesus monkey to estimate quantitatively at the electron microscopic level the intensity of immunoreactivity to an antibody against glutamate over profiles of retinal, cortical, GABAergic synaptic terminals and glial cells. GABAergic terminals were identified directly by immunogold reactivity to a GABA antibody or by ultrastructural features. The results showed that in both of the main subdivisions of the geniculate the densities of immunogold particles over cortical and retinal terminals were about two- to three-fold higher than those over GABAergic terminals or glial profiles. In addition, cortical and retinal terminals showed higher positive correlations of glutamate immunogold particle densities to synaptic vesicle densities than did GABAergic terminals. These differences suggest higher and lower concentrations of glutamate corresponding to transmitter and metabolic pools of this amino acid in axon terminals of retinal and cortical origins versus GABAergic terminals, respectively, in the dorsal lateral geniculate nucleus of the macaque. PMID- 2574427 TI - Direct synaptic contacts of 5-hydroxytryptamine-, neuropeptide Y-, and somatostatin-immunoreactive nerve terminals on the preganglionic sympathetic neurons of the guinea pig. AB - Direct synapses from 5-hydroxytryptamine-, neuropeptide Y-, and somatostatin immunoreactive axon varicosities to the preganglionic sympathetic neurons retrogradely labeled with horseradish peroxidase were observed in the thoracic intermediolateral nucleus of the guinea pig. Symmetric synapses were predominant and both axo-dendritic and axo-somatic contacts were observed. PMID- 2574428 TI - The N-methyl-D-aspartate (NMDA) receptor antagonist, dextrorphan, prevents the neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) in rats. AB - Using the systemically active, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dextrorphan, we explored the role of the NMDA receptor calcium channel complex in the toxic mechanism of action of 3,4 methylenedioxymethamphetamine (MDMA). Rats were treated with MDMA, dextrorphan, or the combination of MDMA and increasing doses of dextrorphan, and then killed 10 days later for the assay of serotonin and dopamine in the striatum, hippocampus, and cortex. Dextrorphan totally prevented the serotonin-depleting effects of MDMA in the straitum, with a lessened but still significant blockade noted in the hippocampus and cortex. These findings may provide a clue to the molecular events underlying MDMA-induced neurotoxicity. PMID- 2574429 TI - Understanding schizophrenia. PMID- 2574430 TI - Synaptic organization of classical neurotransmitter phenotypes in the primate retina. PMID- 2574432 TI - Control of cGMP concentration by calcium ions in frog rods. PMID- 2574431 TI - Peptidergic neurons of the macaque monkey retina. AB - Until recently, peptides were thought to act as neuromodulators in the retina, and the localizations of peptides in wide field amacrine cells, associational cells and interplexiform cells seemed to support this hypothesis. Anatomical studies in the macaque monkey retina, however, found that some types of peptidergic amacrine cells made extensive contacts with bipolar cell axons and retinal ganglion cell dendrites. The most striking exception to the earlier generalizations about retinal peptide function was the localization of immunoreactive cholecystokinin in bipolar cells that contacted short wavelength cones selectively. These results suggested that peptides were not only interacting with the most direct pathway for visual information; they also appeared to be used as transmitters by the neurons that comprise that pathway. Taken with the localizations of peptides in retinal ganglion cells and recent electrophysiological evidence, these findings suggest that peptides can also act more like conventional neurotransmitters. PMID- 2574433 TI - Release of endogenous glutamate from isolated cone photoreceptors of the lizard. PMID- 2574434 TI - Oral trauma in children: a hospital survey. AB - The purpose of this investigation was to determine the type and prevalence of dental injuries seen in a hospital emergency room. Of the 10,436 patients who were treated at the hospital emergency room as a result of a traumatic episode, 765 (7.3%) had sustained injuries to structures of the oral cavity. The leading cause of dental injury was falls, accounting for 55.8% of the injuries. The male to-female ratio of dental injuries was 1.6:1. The peak age group of children with dental injuries was the 1-to-2-year-old age group. Laceration of the lip was the most predominant injury to structures of the oral cavity, accounting for 62.8% of the dental injuries. The peak month for dental injuries was June, and 61.2% of the dental injuries occurred in the home. PMID- 2574435 TI - [Rehabilitative treatment in old and inveterate fracture-dislocations of the bones of the feet]. AB - The authors present the dynamics of the clinico-roentgenologic and biomechanical results of the treatment of 57 patients with late and inveterate dislocation fractures of the bones of the foot using the method of distraction. The analysis of the economic damage has demonstrated that a continuous disturbance in the working ability of the patients with this pathology causes an economic damage to the state averaging 7043.3 +/- 259.2 rubles. The favourable anatomic and functional results obtained in the absolute majority of the patients testify to the effectiveness of the method of distraction treatment. PMID- 2574436 TI - Parathyroid adenoma and nonmedullary thyroid carcinoma association. PMID- 2574437 TI - Effect of lipoteichoic acid on proliferation and differentiation of keratinocytes. AB - Bacterial infection is always found to be associated with cholesteatoma. Accumulation of keratin debris is one of the crucial factors for the growth of cholesteatoma. The effects of lipoteichoic acid, a cell wall component of gram positive bacteria, on the proliferation and differentiation of keratinocytes were studied. Various concentrations of lipoteichoic acid (0 to 100 micrograms/ml) were added to keratinocytes. DNA synthesis and protein synthesis were inhibited by decreasing the incorporation of 3H-thymidine and 3H-leucine into keratinocytes. The effects of lipoteichoic acid on terminal differentiation were then studied by measuring the number of sodium dodecyl sulfate-insoluble cornified cell envelopes and the transglutaminase activity (a marker of terminal differentiation) determined by incorporation of 3H-putrescine into cornified envelopes. These studies showed that lipoteichoic acid stimulated the formation of cornified cell envelopes and transglutaminase activity. These findings suggest that lipoteichoic acid stimulated the terminal differentiation and accumulation of keratin debris and that lipoteichoic acid might have stimulatory effects on the development of cholesteatoma. PMID- 2574438 TI - Infection of bovine T cell clones with genotypically distinct Theileria parva parasites and analysis of their cell surface phenotype. AB - Different stocks and stabilates within a stock of Theileria parva were analysed for genotypic differences and for their effect on the expression of host cell surface antigens following infection of BoT8+ T lymphocyte clones. The parasites were characterized in vitro by hybridization of T. parva-specific DNA probes to Southern blots of endonuclease-digested DNA from the infected T cell clones. Phenotypic changes in the host lymphoblastoid cells before and after infection were examined using lineage-specific monoclonal antibodies which reacted with the differentiation antigens BoT2, BoT4, Bo6, BoT8 and a null cell marker on bovine T cells. Expression of Class I and Class II major histocompatibility complex (MHC) antigens on the cell populations was also assessed. Results of this study indicate that genotypically different parasites exist among and within T. parva stabilates and that the expression of Bo6, BoT8 and the null cell marker was differentially altered by infection with parasites from different stocks or from different stabilates of the same stock. Expression of Class II antigens was significantly increased after infection. Moreover, clones that were derived from the same cell line but had genotypically distinct T. parva parasites, also showed differences in expression of Bo6 and BoT8 and the null cell marker. PMID- 2574440 TI - [The history of the development of the Polish Pediatric Society]. PMID- 2574439 TI - [Functional biochemical changes and their pharmacologic correction by pirroksan in renal ischemia]. AB - Bilateral one-hour ischemia of the kidneys in rats causes essential metabolic shifts in the renal tissues, and diminished intensity of the energetic status as a result of which the intactness of the cell membranes and the main functions of the nephron are disturbed. Pharmacological correction of postischemic disorders by the alpha-adrenergic blocking agent pyrroxane increases the activity of oxidative processes and intensifies the glycolysis rate. Improvement of the energy provision of the nephron function occurs in parallel with restoration of the diuresis level and processes of filtration and reabsorption. PMID- 2574441 TI - [Study of DNA restriction fragment length polymorphism in the diagnosis of mucoviscidosis]. AB - DNA analysis was used to determine heritability of the cystic fibrosis in the family in risk of this disease. It enabled to detect carriers of the cystic fibrosis gene in the examined family and created a basis of the early prenatal diagnosis in case of the planned pregnancy. PMID- 2574442 TI - Modulation of desynchronized sleep through microinjection of beta-adrenergic agonists and antagonists in the dorsal pontine tegmentum of the cat. AB - Brain noradrenergic systems have often been implicated in the regulation of desynchronized sleep (DS). In particular, the reciprocal interaction model of DS generation postulates that noradrenergic neurons in the locus coeruleus inhibit DS-executive cells located in the pontine reticular formation. Accordingly, since noradrenergic inhibition is generally mediated by beta-receptors, one should expect beta-agonists to decrease and beta-antagonists to increase DS. However, systemic injection experiments yielded just the opposite results. Assuming that local microinjection techniques were better suited to testing the model, beta agonists and antagonists were directly infused into the dorsal pontine tegmentum (DPT), a region crucially implicated in the generation of DS. Cats were implanted with standard electrodes for polygraphic recordings and with guide tubes for chemical microinjections. It was observed that, when injected into the DPT, the beta-agonist isoproterenol almost suppressed DS, while the beta-antagonist propranolol consistently enhanced it, the latter largely due to an increased number of DS episodes. These effects were dose-dependent and strictly site specific, since injections in immediately neighbouring structures were ineffective. These results: (a) confirm that cell groups located in the DPT play a key role in the generation of DS, and (b) indicate that they undergo a strong noradrenergic modulation, being inhibited by beta-receptor stimulation and disinhibited by beta-receptor blockade as predicted by the reciprocal interaction model. PMID- 2574443 TI - A two-compartment exploratory model to study anxiolytic/anxiogenic effects of drugs in the rat. AB - The response of a recently described light/dark choice novelty situation to anxiolytic and non-anxiolytic agents as well as to putative anxiogenic drugs was assessed in rats. Diazepam (1.0-10.0 mg/kg, i.p.), chlordiazepoxide (2.5-10.0 mg/kg, i.p.), and pentobarbital (pentobarbitone) (7.5-15.0 mg/kg, i.p.) enhanced rats' activity in the dark and brightly lit compartments as well as crossings between the two, while imipramine (5-20 mg/kg, i.p.) had no effects. None of these drugs changed animal locomotion in activity cages. d-Amphetamine (1.5 mg/kg, i.p.) caused a significant increase in the three parameters used to measure rats' exploratory activity, but the effect was due to an increase in the general activity of the animal. No tolerance to the effects of diazepam developed after daily treatment with 5 mg/kg i.p. for 15 days. Non-sedative and non convulsant doses of putative anxiogenic drugs such as yohimbine (2.5-5.0 mg/kg, i.p.), picrotoxin (2.0-4.0 mg/ml, i.p.) and ethyl-beta-carboline-3-carboxylate (2.5-5 mg/kg, i.p.) reduced the exploratory activity of rats in the dark compartment. The advantages and problems of using this test to identify anxiolytic and anxiogenic drugs are discussed. PMID- 2574445 TI - Carrier detection and prenatal diagnosis in Norrie disease. AB - We report the use of DNA probes to determine carrier status in three young women from a large kindred with Norrie disease. One of the women requested prenatal diagnosis during pregnancy. In this pedigree, Norrie disease was not characterized by a deletion at DXS7. PMID- 2574446 TI - Theoretical and practical implications of a controlled trial of an alpha 2 adrenoceptor antagonist in the treatment of depression. PMID- 2574444 TI - Gender differences in the pharmacodynamics of barbiturates in rats. AB - There is considerable evidence of gender differences in the pharmacokinetics of numerous drugs, particularly in rodents, but very limited information concerning the effect of gender on pharmacodynamic characteristics (concentration-activity relationships). In this study, heptabarbital or phenobarbital was administered to male and female rats and the concentrations of these drugs in the brain, cerebrospinal fluid and serum at onset or offset of loss of righting reflex were determined. For heptabarbital, offset concentrations were determined in Lewis rats and onset concentrations in Wistar rats. Onset concentrations of phenobarbital were determined in Wistar rats. In all cases, the barbiturate concentrations in males were significantly lower than those in females at the pharmacologic endpoint. The biologic (serum) half-life of heptabarbital is much shorter in males (approximately 10 min) than in females (approximately 90 min) and this pharmacokinetic difference is reflected by the considerably longer duration of effect of the drug in females. PMID- 2574447 TI - Selective dopamine D1 and D2 receptor antagonists. PMID- 2574448 TI - Benzodiazepine receptor subtypes and their possible clinical significance. PMID- 2574449 TI - Targets for neurotransmitter receptor research using PET scan: the neuroleptic binding site. PMID- 2574450 TI - Neuroleptic drug levels in erythrocytes and in plasma: implications for therapeutic drug monitoring. PMID- 2574451 TI - Active metabolites of neuroleptics in plasma and CSF: implications for therapeutic drug monitoring. PMID- 2574452 TI - Plasma level monitoring for maintenance neuroleptic therapy. PMID- 2574453 TI - Dose finding and serum concentrations of neuroleptics in the treatment of schizophrenic patients. PMID- 2574454 TI - The potential of positron-emission tomography for pharmacokinetic and pharmacodynamic studies of neuroleptics. PMID- 2574455 TI - Neurotransmitter interactions as a target of drug action. PMID- 2574456 TI - Negative symptoms in schizophrenia: a target for new drug development. PMID- 2574457 TI - 100-kDa polypeptides in peripheral clathrin-coated vesicles are required for receptor-mediated endocytosis. AB - The role of the 100-kDa polypeptide components of clathrin-coated vesicles in endocytosis was investigated by microinjection of specific monoclonal antibodies. Receptor-mediated uptake of transferrin and liposomes was quantitatively inhibited. These results show that the 100-kDa polypeptides are directly involved in localized clathrin assembly at the cell periphery and are markers for the endocytic pathway. This demonstrates an in situ function of these polypeptides and the protein complexes in which they are found. PMID- 2574458 TI - Unusual stage-specific embryonic antigen (TEC-4) defined by a monoclonal antibody to embryonal carcinoma cells defective in the expression of embryoglycan. AB - Most developmentally regulated epitopes identified on embryonal carcinoma cells and murine preimplantation embryos are associated with a glycoprotein-bound large glycan called embryoglycan. To prepare monoclonal antibodies recognizing other, less immunogenic stage-specific embryonic epitopes, we used embryoglycan-negative embryonal carcinoma cells P19XT.1.1 as immunogen. One monoclonal antibody prepared by this strategy was found to react specifically with mouse embryonal carcinoma and embryo-derived stem cell lines. The target epitope, TEC-4, was found to be expressed on eggs and two-cell embryos but was undetectable on later stages of mouse embryos and adult mouse tissues. NaDodSO4/PAGE of immunoaffinity isolated antigen revealed that TEC-4 epitope is associated with glycoproteins of apparent Mr 120,000 and 240,000. The epitope was resistant to oxidation by sodium periodate and to digestion by endoglycosidase F but was sensitive to treatment with protein-denaturing agents and proteases, which suggested that the epitope is located in the protein moiety of the molecule. In the course of retinoic acid induced differentiation of embryonal carcinoma cells the epitope disappeared before the onset of morphological differentiation. The combined data indicate that TEC-4 is an unusual stage-specific embryonic antigen that may be amenable to direct genetic analysis. PMID- 2574459 TI - Active late-appearing variable surface antigen genes in Trypanosoma equiperdum are constructed entirely from pseudogenes. AB - The expression of genes coding for variable surface glycoproteins (VSGs) in Trypanosoma equiperdum is linked to duplicative transpositions of silent, basic copy sequences into telomere-linked expression sites. Examination of three independently derived late-appearing trypanosome clones expressing VSG-78 revealed that the expressed gene in all cases is composed of sequences derived from three or four individual silent genes. The 182 base pairs at the 3' end of the coding sequence are derived from one silent gene, the 3' donor. The remaining 5' segment is a mosaic structure containing variable-length segments derived from two, or perhaps three, related silent genes. All of the silent genes that participate in the construction of the VSG-78 expression-linked copy (ELC) genes contain multiple stop codons and are unable to code for VSGs. Individual silent pseudogenes complement one another in the mosaic structure of the 5' portions of the ELC genes and create functional VSG genes. The joining of the 3' and 5' portions of the composite genes occurs in short regions of homology and suggests a mechanism by which the ordered expression of the VSG genes is generated. PMID- 2574460 TI - Single-sperm typing: determination of genetic distance between the G gamma-globin and parathyroid hormone loci by using the polymerase chain reaction and allele specific oligomers. AB - The frequency of recombination between the G gamma-globin (HBG2) and parathyroid hormone (PTH) loci on the short arm of human chromosome 11 was estimated by typing greater than 700 single-sperm samples from two males. The sperm-typing technique employed involves the polymerase chain reaction and allele-specific oligonucleotide hybridization. Our maximum likelihood recombination fraction estimate of 0.16 (95%) confidence interval, 0.13-0.19) falls well within previous estimates based on family studies. With current technology and a sample size of 1000 sperm, recombination fractions down to approximately 0.009 can be estimated with statistical reliability; with a sample size of 5000 sperm, this value drops to about 0.004. Reasonable technological improvements could result in the detection of recombination frequencies less than 0.001. PMID- 2574461 TI - Allelic sequence variations in the hypervariable region of a T-cell receptor beta chain: correlation with restriction fragment length polymorphism in human families and populations. AB - Direct sequence analysis of the human T-cell antigen receptor (TCR) V beta 1 variable gene identified a single base-pair allelic variation (C/G) located within the coding region. This change results in substitution of a histidine (CAC) for a glutamine (CAG) at position 48 of the TCR beta chain, a position predicted to be in the TCR antigen binding site. The V beta 1 polymorphism was found by DNA sequence analysis of V beta 1 genes from seven unrelated individuals; V beta 1 genes were amplified by the polymerase chain reaction, the amplified fragments were cloned into M13 phage vectors, and sequences were determined. To determine the inheritance patterns of the V beta 1 substitution and to test correlation with V beta 1 restriction fragment length polymorphism detected with Pvu II and Taq I, allele-specific oligonucleotides were constructed and used to characterize amplified DNA samples. Seventy unrelated individuals and six families were tested for both restriction fragment length polymorphism and for the V beta 1 substitution. The correlation was also tested using amplified, size-selected, Pvu II- and Taq I-digested DNA samples from heterozygotes. Pvu II allele 1 (61/70) and Taq I allele 1 (66/70) were found to be correlated with the substitution giving rise to a histidine at position 48. Because there are exceptions to the correlation, the use of specific probes to characterize allelic forms of TCR variable genes will provide important tools for studies of basic TCR genetics and disease associations. PMID- 2574462 TI - Arylsulfatase A pseudodeficiency: loss of a polyadenylylation signal and N glycosylation site. AB - Metachromatic leukodystrophy is a metabolic disorder caused by the deficiency of arylsulfatase A. Deficiency of this enzyme is also found in apparently healthy individuals, a condition for which the term pseudodeficiency was introduced. The arylsulfatase A (cerebroside-3-sulfate 3-sulfohydrolase; EC 3.1.6.8) (ASA) encoding gene was isolated from an individual homozygous for the ASA pseudodeficiency allele. Sequence analysis revealed two A----G transitions. One changes Arg-350 to serine, which leads to the loss of a utilized N-glycosylation site. This loss explains the smaller size of ASA in ASA pseudodeficiency fibroblasts. The introduction of Ser-350 into normal ASA cDNA does not affect the rate of synthesis, the stability, or the catalytic properties of ASA in stably transfected baby hamster kidney cells. Therefore, the loss of the N-linked oligosaccharide does not contribute to the reduction of ASA activity in ASA pseudodeficiency. The other A----G transition changes the first polyadenylylation signal downstream of the stop codon from AATAAC to AGTAAC. The latter causes a severe deficiency of a 2.1-kilobase (kb) mRNA species. The deficiency of the 2.1 kb RNA species provides an explanation for the diminished synthesis of ASA seen in pseudodeficiency fibroblasts. Amplification of genomic DNA and hybridization with allele-specific oligonucleotides detected both mutations in four unrelated individuals with ASA pseudodeficiency. PMID- 2574463 TI - Circumscribed changes of the cerebral cortex in neuropsychiatric disorders of later life. AB - The extent and distribution of biochemical abnormalities thought to reflect disorders of subpopulations of neurons have been determined in the cerebral cortex from brains of patients with Alzheimer-type dementia and depressive illness who died of natural causes. In dementia, loss of gray matter from areas of the parietal and temporal lobes is most obvious. In depression, these areas are not affected, but the pars opercularis and temporal pole are smaller than in controls. Results expressed per unit mass of total protein indicate selective reductions in both disorders of serotonin 2 recognition sites in all areas examined and of somatostatin content in only the temporal pole of the six areas examined. In dementia alone a selective loss was found of somatostatin content of the superior parietal lobule and of serotonin 1A sites and choline acetyltransferase activity in all areas examined. Results for depression expressed per entire area indicate additionally reduced somatostatin content and serotonin 1A sites in the pars opercularis and serotonin 1A sites in the temporal pole. These multiple analyses performed on each sample provide further support for a prominent disorder of pyramidal neurons in dementia as well as more evidence for alterations in cortical neurons in depression, either as a result of the disease itself or its treatment. PMID- 2574464 TI - An explanation for the purported excitation of piriform cortical neurons by N acetyl-L-aspartyl-L-glutamic acid (NAAG). AB - The excitation of piriform cortical neurons by iontophoresis of N-acetyl-L aspartyl-L-glutamic acid (NAAG) isolated from rat brain is frequently cited as major support for the possible neurotransmitter role of NAAG in the CNS [ffrench Mullen, J. M. H., Koller, K., Zaczek, R., Coyle, J. T., Hori, N. & Carpenter, D. O. (1985) Proc. Natl. Acad. Sci. USA 82, 3897-3900]. However, we have been unable to reproduce this observation using synthetic NAAG, and instead we offer an alternative explanation. In our experiments, iontophoresis of the sodium salt of synthetic NAAG did not induce single-unit spiking at sites in slices of rat piriform cortex that responded vigorously to L-glutamate. In contrast, iontophoresis of the potassium salt of synthetic NAAG or of potassium ions alone induced single unit activity. The responses to both NAAG/KCl and KCl alone were inhibited by L-2-amino-4-phosphonobutanoic acid and desensitized rapidly, as previously reported for NAAG. These results suggest that residual potassium ions, remaining after the original purification of NAAG, were responsible for the excitations attributed to NAAG. PMID- 2574466 TI - The Florey lecture, 1989. Self-tolerance: the key to autoimmunity. AB - 'Horor autotoxicus', as it was termed by Erhlich, is a rare clinical event despite the genetic potential of every individual to mount immune responses to self-antigens. This can be explained by the fact that the developing immune system learns to recognize self-antigens and to tolerate them. The key to autoimmunity therefore lies in unravelling the mechanisms of self-tolerance. Studies of conventional models of unresponsiveness have failed to provide a definitive answer owing to the difficulty in controlling for the large number of antigen-related variables associated with self-tolerance and in following the fate of individual clones of self-reactive lymphocytes which emerge in very low numbers from the pre-immune repertoire. These problems have now been overcome by creation of transgenic mice tolerant to endogenous antigens and containing high frequencies of autoreactive T or B lymphocytes. According to the results obtained to date, different mechanisms of tolerance induction operate for self-reactive T lymphocytes compared with B lymphocytes. Thus self-tolerance in T lymphocytes appears to depend largely on clonal deletion within the thymus. By contrast, self reactive B lymphocytes are functionally silenced without undergoing deletion provided that the transgenic B lymphocytes express both IgM and IgD on their surfaces. This dichotomy makes good sense given that the T-lymphocyte repertoire once shaped within the thymus is not subject to further mutation whereas antigen receptors on mature B lymphocytes undergo hypermutation in the periphery. PMID- 2574467 TI - Unifying shading and texture through an active observer. AB - Shading (variations of image intensity) provides an important cue for understanding the shape of three-dimensional surfaces from monocular views. On the other hand, texture (distribution of discontinuities on the surface) is a strong cue for recovering surface orientation by using monocular images. But given the image of an object or scene, what technique should we use to recover the shape of what is image? Resolution of shape from shading requires knowledge of the reflectance of the imaged surface and, usually, the fact that it is smooth (i.e. it shows no discontinuities). Determination of shape from texture requires knowledge of the distribution of surface markings (i.e. discontinuities). One might expect that one method would work when the other does not. I present a theory on how an active observer can determine shape from the image of an object or scene regardless of whether the image is shaded, textured, or both, and without any knowledge of reflectance maps or the distribution of surface markings. The approach is successful because the active observer is able to manipulate the constraints behind the perceptual phenomenon at hand and thus derive a simple solution. Several experimental results are presented with real and synthetic images. PMID- 2574465 TI - Somatostatin-14 and somatostatin-28 induce opposite effects on potassium currents in rat neocortical neurons. AB - The prosomatostatin-derived peptides somatostatin-14 (Som-14) and somatostatin-28 (Som-28) are believed to act as neurotransmitters in the central nervous system. To examine possible mechanisms by which these peptides induce their physiological actions in brain, the effects of Som-14 and Som-28 on voltage-dependent K+ currents in rat cerebral cortical neurons in culture were examined by using whole cell patch-clamp techniques. Som-14 increased a delayed rectifier K+ current (IK) in the cortical neurons, while Som-28 reduced IK in the neurons, both in a concentration-dependent manner. Som-14 and Som-28 could induce opposite changes in IK in the same neurons. Elevating intracellular cAMP in the cortical neurons did not modify the effects of Som-14 or Som-28 on IK, indicating that the peptides can regulate this ionic current through cAMP-independent mechanisms. Pretreatment of the neocortical cells with pertussis toxin, which inactivates inhibitory GTP-binding proteins, abolished both Som-14 and Som-28 modulation of IK, indicating that Som-14 and Som-28 receptors are coupled to IK via GTP-binding proteins. These studies show that Som-14 and Som-28 can induce opposite biological effects, suggesting that Som-14 and Som-28, acting through distinct receptors, may function as different neurotransmitters or neuromodulators. PMID- 2574468 TI - Immuno-ultrastructural localization of sodium channels at nodes of Ranvier and perinodal astrocytes in rat optic nerve. AB - Immuno-electron microscopic localization of sodium channels at nodes of Ranvier within adult optic nerve was demonstrated with polyclonal antibody 7493. The 7493 antisera, which is directed against purified sodium channels from rat brain, recognizes a 260 kDa protein in immunoblots of the crude glycoprotein fraction from adult rat optic nerve. Intense immunoreactivity with 7493 antisera was observed at nodes of Ranvier. Axon membrane at the node was densely stained, whereas paranodal and internodal axon membrane did not exhibit immunoreactivity. The axoplasm beneath the nodal membrane displayed variable immunostaining. Neither terminal paranodal oligodendroglial loops nor oligodendrocyte plasmalemma were immunoreactive with 7493 antisera. However, perinodal astrocyte processes exhibited intense immunoreactivity with the anti-sodium channel antisera. Optic nerves incubated with pre-immune sera, or with 7493 antisera that had been pre adsorbed with purified sodium channel protein, displayed no immunoreactivity. These results demonstrate localization of sodium channels at high density at mammalian nodes of Ranvier and in some perinodal astrocyte processes. The latter observation offers support for an active role for perinodal astrocyte processes in the aggregation of sodium channels within the axon membrane at the node of Ranvier. PMID- 2574469 TI - The biogenesis of the cyanellae of Cyanophora paradoxa. I. Polypeptide composition of the cyanellae. AB - Based on polypeptide separation, protein purification and immunoblotting techniques using heterologous antibodies, we have been able to identify several photosynthetically important polypeptide components of the cyanellae of Cyanophora paradoxa. Cytochrome c-552 and ferredoxin have been purified to electrophoretic homogeneity and exhibit apparent molecular masses of 10.5 and 9.0 kDa, respectively. Cytochrome c-552 has an isoelectric point of pH 4.2 +/- 0.1. Plastocyanin was immunologically and spectrally undetectable even in cells grown in the presence of Cu2+. Polypeptides for cytochromes f, b-6 and c-552 have been located in electrophoretically resolved thylakoid samples by using the TMBZ staining procedure. Intact phycobilisomes have been purified and characterized with respect to polypeptide composition and absorption and emission spectra. Photosystems I and II have been isolated and characterized with respect to their photochemical activities, spectral characteristics and polypeptide composition. Photochemically active PS I complexes fluoresce maximally at 720 nm at 77 K and comprise five polypeptide subunits resolved under denaturing conditions with apparent molecular masses of 66, 21, 18, 14 and 11 kDa. PS II core complexes mediate light-dependent 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU)-sensitive electron transfer between 1,5-diphenylcarbazide (DPC) and 2,6 dichlorophenolindophenol (DPIP) at rates of 140-200 mumol h-1 mg-1 chlorophyll. These complexes exhibit absorption maxima at 436 and 673 nm and show fluorescence emission maxima at 685 and 695 nm at 77 K. Rubisco was separated by two dimensional electrophoresis and immunologically characterized. PMID- 2574470 TI - The biogenesis of the cyanellae of Cyanophora paradoxa. II. Pulse-labelling of cyanellar polypeptides in the presence of transcriptional and translational inhibitors. AB - Cycloheximide and chloroamphenicol, specific inhibitors of protein translation in the cytoplasmic and cyanellar compartments, respectively, of Cyanophora paradoxa, have been employed in 30 min pulse-labelling experiments by using [NaH-14C]O3 to label total cell proteins in vivo. Cyanellae purified from host cell lysates were separated into soluble and thylakoid fractions and analysed by one- and two dimensional polyacrylamide gel electrophoresis (PAGE) to determine the distribution of radioactivity in the cyanellar polypeptides. Analysis of the autoradiograms of electrophoretically resolved proteins of the cyanellae indicates that about 70% of the total number of cyanellar proteins visualized in the controls are synthesized on cytoplasmic ribosomes. The majority (81%) of the soluble cyanellar proteins appear to be cytoplasmically synthesized. In contrast, the majority (70%) of the thylakoid proteins are synthesized within the cyanellae. The observations also suggest that the polypeptides synthesized within the cyanellae include species that are the most abundant and rapidly turned over. A number of the polypeptides previously identified have now been characterized with regard to their sites of synthesis. In addition, we report on labelling experiments involving rifampicin, a specific inhibitor of cyanellar transcription, which indicate that different mRNAs within the cyanellae have markedly different stabilities. PMID- 2574471 TI - The biogenesis of the cyanellae of Cyanophora paradoxa. III. In vitro synthesis of cyanellar polypeptides using separated cytoplasmic and cyanellar RNA. AB - RNA from Cyanophora paradoxa was separated into cytoplasmic and cyanellar fractions by using a combination of subcellular fractionation and oligo-dT chromatography. In vitro translation of the separated cytoplasmic and cyanellar RNAs in a rabbit reticulocyte lysate system in the presence of [35S]methionine resulted in the incorporation of radiolabel into electrophoretically distinct sets of polypeptides. Monospecific and polyspecific antibodies that react with cyanellar polypeptides were used to probe the in vitro translation products by indirect immunoprecipitation by using Staphylococcus protein A conjugated to Sepharose beads. The results indicate that linker polypeptide L1 of the phycobilisome, the gamma subunit of coupling factor CF1, and subunit II of PS I are synthesized in the cytoplasm as precursor molecules that are 5-8 kDa larger than their mature sizes. Antibodies directed against the psbA gene product (the D1 protein) precipitated a polypeptide found in the translation products of the cyanellar RNA-directed reactions, which is about 1.5 kDa larger than the mature protein. PMID- 2574472 TI - Predictors of response to high dose antipsychotics in chronic schizophrenics. AB - Significant numbers of chronic schizophrenic patients do not experience sufficient symptom relief from usual doses of antipsychotic medication. Clinicians must decide if high doses of antipsychotics should be tried. In this study baseline symptoms, drug levels, and the symptomatic effects of an acute stimulant challenge were examined before 14 subjects received a 50% increase in their antipsychotic dosing. The group as a whole did not improve. Several individuals with lower drug levels, high baseline hallucinations, and stimulant induced improvement in hallucinations improved mildly after 3 weeks on the higher antipsychotic dose. PMID- 2574473 TI - Arylsulfatase A activity among psychotic patients. PMID- 2574474 TI - Midsagittal cortical pathomorphology of schizophrenia: a magnetic resonance imaging study. AB - Forty schizophrenic patients and 17 normal controls underwent magnetic resonance imaging (MRI) of the brain. All subjects were consenting males under 50 years old. Enlargement of the septum pellucidum in schizophrenics was confirmed. This finding was significantly related to a family history of the disorder. Although this study could not confirm a decreased frontal:brain ratio (FBR) in schizophrenics as reported by Andreasen et al. (1986), a negative correlation between FBR and negative symptoms was seen. No significant differences in other cerebral substructures, cerebellar vermis, or fourth ventricle of the midsaggital cut were seen between schizophrenics and normal controls. However, it is of interest that a small cerebellar vermis:brain ratio was associated with good therapeutic response to neuroleptics in schizophrenics. All these findings suggest that combining morphological changes in the brain as illustrated by MRI with clinical variables may provide a useful new approach to the subclassification of schizophrenia. PMID- 2574475 TI - Cognitive impairment, clinical course and treatment history in out-patients with bipolar affective disorder: relationship to tardive dyskinesia. AB - Clinical, neuropsychological and psychopharmacological characteristics were investigated for their ability to distinguish individuals with and without involuntary movements (tardive dyskinesia), among a population of 40 out-patients with bipolar affective disorder and a history of exposure to neuroleptics and lithium. Impaired performance on a test of cognitive flexibility bore the primary association with both the presence and the severity of involuntary movements. The additional relationships identified emphasized further that individual vulnerability to involuntary movements appeared to be associated not with greater duration or dosage of treatment, but with features of the bipolar illness, including number and type of affective episodes, for which that treatment was prescribed. PMID- 2574476 TI - Rats self-administer sufentanil in aerosol form. AB - An ultrasonic nebulizer was used to create a drug vapor to develop an animal model for the self-administration of inhaled nonvolatile psychoactive drugs. An aerosol mist of a sufentanil citrate solution (10, 25, 50, or 75 micrograms/ml) was delivered to rats in response to lever presses on an FR 5 schedule of reinforcement. The speed of acquisition of the operant response and the selectivity of the drug effect were examined. Rats given access to sufentanil vapor (50 or 75 micrograms/ml) in 13-15 h overnight training sessions reached an average of one reinforcement per hour on an FR 5 schedule of reinforcement significantly sooner than did rats given access to water vapor. Responding maintained by sufentanil during 2-h daily testing sessions was dose dependent at 25, 50, and 75 micrograms/ml. Substituting water vapor for each of the four sufentanil concentrations significantly reduced responding within 5-20 sessions. Naloxone (1 mg/kg, IP) decreased responding for sufentanil to the level attained under water vapor. Presentation of drugs in aerosol form thus provides reasonable means of demonstrating in animals the reinforcing properties of non-volatile drugs by the pulmonary or intranasal route. PMID- 2574477 TI - The effects of intrathecal administration of the dopamine agonist apomorphine on penile reflexes and copulation in the male rat. AB - Relatively high doses of systemically administered apomorphine inhibit penile reflexes. It is possible that these inhibitory effects are due, at least in part, to actions of apomorphine on the lumbosacral spinal cord. The present experiments examined this possibility by injecting apomorphine (10 and 50 micrograms/5.0 microliters vehicle) into the lumbosacral subarachnoid space through chronic, indwelling cannulae. Such injections impaired ex copula penile reflexes, slowed the rate of copulation, and decreased the number of intromissions preceding ejaculation. These results suggest that lumbosacral cord dopamine receptors may normally regulate male sexual performance. PMID- 2574478 TI - MDMA produces stimulant-like conditioned locomotor activity. AB - Daily administration of a drug in a distinctive environment establishes contingencies that support Pavlovian conditioning. Environmental cues that are paired with the drug injection and that predict the onset of drug action can become conditioned stimuli. Ultimately, the conditioned stimuli come to predict the availability of drug and develop the potential to engender conditioned drug responses. Various psychostimulant drugs can produce conditioned locomotion when tested in the presence of environmental cues that were repeatedly associated with the drug experience. The ability of amphetamine and cocaine to produce conditioned locomotion was demonstrated in the present study. Stimulant-like properties of methylenedioxy-methamphetamine (MDMA) have been reported in locomotor paradigms, drug discrimination procedures, and human subjective questionnaires. MDMA (5 mg/kg), paired for 5 days to a distinct environment signalled by the presence of a distinct odor, produced enhanced locomotion during a test probe with the odor alone indicating that MDMA can also produce conditioned locomotion. The observation that the stimulus properties of MDMA can also become associated with environmental cues supports the hypothesis that some of the behavioral effects of MDMA resemble those of other classical psychostimulants such as amphetamine and cocaine. PMID- 2574479 TI - Prevention of the analgesic consequences of social defeat in male mice by 5-HT1A anxiolytics, buspirone, gepirone and ipsapirone. AB - Behavioural and pharmacological studies have suggested that anxiety may be an important factor in the initiation of non-opioid analgesia in defeated male mice. In the present study, the effects of three 5-HT1A anxiolytics (buspirone, ipsapirone and gepirone) on basal nociception and defeat analgesia were examined. Results show that the analgesic consequences of social defeat were potently blocked by all three compounds, with a rank-order potency (minimum effective doses) of ipsapirone (0.05 mg/kg) greater than gepirone (0.1 mg/kg) greater than buspirone (0.5 mg/kg). These inhibitory effects on defeat analgesia were observed in the absence of intrinsic activity on basal nociception (tail-flick assay). When administered alone, (-)pindolol produced biphasic effects on defeat analgesia with enhancement at 0.5 mg/kg and inhibition at 5.0 mg/kg. Lower doses of (-)pindolol (0.05 and 0.25 mg/kg) which did not affect defeat analgesia when administered alone, totally blocked the inhibitory effects of ipsapirone (0.5 mg/kg). Data are discussed in relation to the involvement of 5-HT1A receptor mechanisms in this adaptive form of pain inhibition. PMID- 2574481 TI - Striatal dopamine receptor occupancy during and following withdrawal from neuroleptic treatment: correlative evaluation by positron emission tomography and plasma prolactin levels. AB - The percentage occupation of striatal dopamine D2 receptors has been evaluated in 25 patients using 76Br-bromospiperone positron emission tomography (PET) and prolactin plasma levels (PRL) during oral neuroleptic treatment (11 studies), 1 90 days following discontinuation of such treatment (16 studies), and 1-120 days after last intramuscular administration of depot neuroleptics (nine studies). The PET-estimated occupation was highly significantly correlated in a sigmoid-like fashion to the logarithm of the chlorpromazine-equivalent dose of oral neuroleptics (suggesting a strict dose-occupation relationship during oral neuroleptic treatment and supporting the D2-mediated hypothesis of neuroleptic action), while PRL was weakly related to daily dosage. Following withdrawal, return to normal receptor availability, as estimated by PET, occurred within 5-15 days (suggesting that protracted effects of neuroleptics after withdrawal are not due to sustained D2 receptor occupation), but PRL values fell even more rapidly. Efficient treatment with depot neuroleptics resulted in marked PET-estimated D2 receptor occupation, stable over the whole 4-week drug-administration interval, suggesting that longer intervals could be appropriate; PRL values bore no relationship to PET-estimated occupation, indicating variable intersubject tolerance to neuro-endocrine dopamine blockade. Overall, PET was much more sensitive than PRL to estimate striatal D2 receptor occupation in vivo. PMID- 2574480 TI - CCK-8 injected into the nucleus accumbens attenuates the supersensitive locomotor response to apomorphine in 6-OHDA and chronic-neuroleptic treated rats. AB - Postsynaptic dopamine-cholecystokinin (CCK) interactions in the nucleus accumbens were studied in two behavioral preparations of DA receptor supersensitivity: chronic-neuroleptic treated and 6-hydroxydopamine (6-OHDA) denervated rats. Subcutaneous (SC) injections of apomorphine (APO; 0.15 mg/kg) in experiment 1 produced marked hyperlocomotion in rats following 12 days of pretreatment with cis-[Z]-flupenthixol (2 mg/kg; twice per day). Bilateral intra-accumbens (N.Acc.) microinjections of CCK-8 (2 ng and 2 micrograms) reliably reduced APO-stimulated hyperlocomotion. An intermediate CCK dose (20 ng) was without effect. No change in APO responsivity following chronic vehicle treatment was observed and the baseline APO response was not altered by CCK at any dose. Denervation of mesolimbic dopamine (DA) terminals by intra-N.Acc. injections of 6 hydroxydopamine (6-OHDA; 8 micrograms/side) in experiment 2 similarly resulted in intense locomotor hyperactivity after APO stimulation (0.1 mg/kg; SC). Bilateral intra-N.Acc. injections of CCK-8 (1, 10, 100 ng, and 1 micrograms) significantly attenuated the supersensitive locomotor response to APO. As in experiment 1, CCK produced "biphasic" dose-response effects with strong attenuation that persisted throughout the entire 60-min test at both high (1 microgram) and low (1 ng) doses. Intermediate CCK doses (10 and 100 ng) produced only short-term reductions in activity. Hypomotility induced by APO in SHAM-lesioned rats was not effectively reversed by CCK treatments. CCK had no effect on unstimulated baseline locomotor activity in either 6-OHDA or SHAM-lesioned rats. These results provide further evidence that CCK-8 modulates mesolimbic DA activity by functionally opposing the postsynaptic effects of DA in the region of the nucleus accumbens. PMID- 2574482 TI - Riluzole antagonizes the anxiogenic properties of the beta-carboline FG 7142 in rats. AB - The possible anxiolytic activity of riluzole, a drug which interferes with glutamic acid neurotransmission, was studied in rats using operant conflict procedures. In both "anxiolytic" and "anxiogenic" procedures, riluzole alone did not possess any anticonflict or proconflict effect at doses of 2 and 4 mg/kg PO. Riluzole over the same dose-range was able to antagonize the well known proconflict effect of the beta-carboline derivative FG 7142, an inverse agonist at the GABA-benzodiazepine-chloride ionophore receptor complex. This effect could be related to the possible interaction of riluzole with glutamic acid neurotransmission, since it has been demonstrated previously that beta-carbolines such as DMCM and beta-CCM were able to deplete the levels of aspartic and glutamic acids in rodent cortex, perhaps by enhancing release of amino acid neurotransmitters. If one subscribes to the hypothesis that the anxiety induced by beta-carboline derivatives is related to depression, riluzole might be of value in the treatment of anxiety related to depression. PMID- 2574484 TI - Predicting the outcome of acute stroke: do multivariate models help? AB - Data collected by a single observer on 362 patients taking part in an acute intervention trial were used to derive simple methods of predicting outcome in conscious stroke victims. The effectiveness of these univariate methods was then compared with that of multivariate models based on discriminant function analysis. The multivariate models were somewhat better at predicting death within the first month in newly-admitted patients, and in predicting lack of functional improvement between one and six months in those still in hospital at one month. Even so, these predictions could not be made with certainty and the improvements in probability offered by multivariate over univariate analysis are unlikely to be of practical benefit to the clinician. Single variables such as power in the affected arm and continence were as good as the discriminant functions at predicting discharge within the first month and first six months, respectively. The predictive power of these single simple clinical variables was validated in a separate group of 277 stroke patients. The various proposed methods of prognostication in stroke need to be compared in prospective studies, but until this is done, we recommend a simple approach using the best available clinical information. PMID- 2574485 TI - [New waves in rice breeding through molecular technics]. PMID- 2574483 TI - Effects of carbamazepine on dopamine function in rodents. AB - Carbamazepine (CBZ), a drug with acute antimanic and prophylactic activity in the treatment of manic depressive psychosis, was administered to rats in their diet, resulting in plasma levels of 5-10 micrograms/ml, which is within the human therapeutic range. Chronic CBZ (14 days) did not increase hyperactivity stimulated by the dopamine agonist apomorphine (1.0 mg/kg or 0.5 mg/kg), or to methylamphetamine (0.75 mg/kg), a dopamine releasing agent. Chronic CBZ failed to attenuate the development of enhanced sensitivity to methylamphetamine (0.75 mg/kg) produced by chronic haloperidol (2 mg/kg daily), in contrast to the known attenuation produced by lithium. Pretreatment with CBZ attenuated the hypoactivity produced by apomorphine (0.08 mg/kg), suggesting possible decreased sensitivity of presynaptic dopamine auto-receptors inhibiting dopamine release. Pretreatment with CBZ for 14 days decreased accumulation of L-dopa after administration of NSD 1015 (100 mg/kg IP), an amino acid decarboxylase inhibitor, in the frontal cortex, suggesting decreased dopamine synthesis. These findings suggest that the anti-manic activity of CBZ is neither related to a dopamine blocking action similar to that of neuroleptics, or to an attenuation of dopamine regulatory mechanisms similar to that of lithium. However, chronic CBZ may have some effects on presynaptic dopamine function, indicated by reduced sensitivity of presynaptic dopamine receptors, which may be related to its therapeutic action. PMID- 2574486 TI - Allergic rhinitis: a rational choice of treatment. PMID- 2574487 TI - [Coral substituted for bone grafting in posterior vertebral arthrodesis in children. Initial results]. AB - The authors used natural coral as a substitutive element to bone supply in children in need of posterior vertebral graft. The use of natural coral was part of a protocol aiming at diminishing peroperative bleeding, and as far as possible, at doing away with resorting to homotransfusion. After reviewing the biological, experimental and clinical bases, the authors studied 49 cases of posterior vertebral fusion instrumented with the Cotrel-Dubousset device and with natural coral grafts. Results were appraised with X-ray in all cases, 5 times with scintigraphies and 7 times with biopsies and were encouraging: coral behaves quite similarly to the usual bone graft. From their experience the authors describe how coral is to be used and consider that the use of this substitutive element should spread in the future under various forms. PMID- 2574488 TI - [Changes induced by simple jejuno-ileal by-pass models in the distribution of D cells producing intestinal somatostatin. Experimental study]. AB - Cells that produce somatostatin are widely distributed throughout the digestive tube. They are found in the stomach, small bowel, large bowel and pancreas. The authors used 54 Wistar rats, with an approximate weight of 300 gr, to evaluate the possible variations of the D cell population in isolated and functional intestinal segments, using jejuno-ileal bypass as a model. Rats were divided into three groups, a control group and two groups in which simple derivation techniques were performed following the techniques of Payne and DeWind, and Scott. Rats were sacrificed after 7, 30 and 90 days in subgroups of six animals. Macroscopic, microscopic and ultrastructural studies were carried out. Cells were specifically stained using immunocytochemical techniques (PAP). The corresponding values of the mucous areas were obtained using a computerized image analyzer (Quantimet 800) and then the number of D cells per mm2 mucosa was calculated. The results show a decrease in the number of D cells per mm2 of mucosa in the functional intestinal segments and degranulation of these cells, coinciding with the existence of large areas of rough endoplasmic reticulum (sign of cellular hyperactivity). PMID- 2574489 TI - [Acid-related pathology and prolonged continuous gastric pH monitoring. Physiopathologic findings and therapeutic implications]. AB - Long-term measurement of gastric acidity is useful for the investigation of acid related disorders of the upper gastrointestinal tract and for the evaluation of antisecretory drugs. The assessment of this function with intragastric minielectrodes connected to ambulatory solid-state recorders is increasingly being used and is replacing the traditional aspirative methods. Antimony and glass electrodes provide equivalent results in vivo and thus they can be used interchangeably in every clinical condition. In normal subjects and in patients with acid-related disorders this technique has the great advantage to allow us an accurate knowledge not only of the level but also of the variations of gastric acidity over time, in relation to usual events of daily life. Clinical pharmacological studies permit to define exactly the potency and the duration of action of antisecretory compounds, the effects of various doses of the same drug and their best administration time. PMID- 2574490 TI - Analysis of T-cell subpopulations in human IL-2R alpha transgenic mice: expansion of Thy1.2- thymocytes and depletion of double-positive T-cell precursors. AB - Transgenic mice carrying the human IL-2R alpha/p55 gene under the control of the SV40 enhancer/promoter were used to study the relevance of IL-2R in T-cell development. Serological analysis of the mouse lines obtained indicated transient, regulated expression of the human p55 gene, mainly confined to the early thymus, but which was also detected in lower amounts in the spleen. These mice showed degenerated thymuses, with an increased number of Thy1.2- double negative precursor cells; they also had specific depletion of double-positive thymocytes. Transgene expression led to an increased number of intermediate affinity IL-2 receptors (possibly ascribed to deregulated expression of IL-2R beta/p75) in transgenic thymocytes older than 12 weeks. These results suggest the occurrence of strong linkage between the IL-2/IL-2R system elements and thymic differentiation/maturation; they lend support to the idea of functionality of IL 2R expressed transiently in early stages of T-cell development. PMID- 2574491 TI - Effects of thiazinamium chloride on human isolated bronchial muscle preparations. AB - In human bronchial muscle preparations contracted with histamine, the rank order potency for the relaxant effect of various antagonists was: thiazinamium chloride less than tripelennamine less than atropine (pD2 values: 7.78, 6.16 and greater than 4 for each antagonist, respectively). These antagonists also relaxed human isolated bronchial muscle preparations contracted with acetylcholine. The rank order potency was: atropine less than thiazinamium chloride less than tripelennamine (pD2 values: 7.76, 6.94 and 4.05, respectively). Tripelennamine and thiazinamium chloride displaced histamine concentration-effect curves and atropine and thiazinamium chloride antagonized acetylcholine curves in human isolated bronchial muscle preparations. These results suggest that thiazinamium chloride may have important therapeutic value in airways disease since this drug not only relaxed human isolated airway muscle preparations but also antagonized contractile responses in these tissues to both histamine and acetylcholine. PMID- 2574492 TI - [Exercise testing of the chronic effects of bunazosin hydrochloride on dilated cardiomyopathy]. AB - Bunazosin hydrochloride was administrated in 3-mg oral doses to the 10 patients (6 males and 4 females, average 49.9 years) with dilated cardiomyopathy (DCM) of class II in the NYHA functional classification. Then we observed the changes in their hemodynamics at rest, chest X-ray, echocardiography, humoral factors and symptom-limited exercise tolerance with treadmill testing before treatment and 4 and 8 weeks after administration. All but the left ventricular end-diastolic diameter after 8 weeks were unchanged. Of the humoral factors, only aldosterone decreased significantly during the treatment. On the other hand, the duration of symptom-limited exercise was prolonged significantly, and for a given exercise load, a reduction of heart rate and systolic blood pressure as well as a drop in the PRP occurred at 8 weeks after administration. Therefore, bunazosin appears to improve cardiac function and exercise tolerance in the patients with DCM, at dosages which do not affect hemodynamics at rest. PMID- 2574493 TI - [A severe dystonic reaction in acute Torecan poisoning]. AB - Phenothiazines are a widely used group of drugs for medical practice. Some of them, including Torecan, may induce dystonic reactions of severe aspect which may lead to errors of diagnosis. Although in the paediatric practice this drug is but seldom used the possibility of intoxications exists when it is used without a medical prescription. The authors present two cases where neurological manifestations occurred, as severe, dystonic phenomena, that had a favourable evolution, under adequate therapy. PMID- 2574495 TI - [The treatment of rheumatoid polyarthritis using salazosulfapyridine. Apropos of 23 cases]. PMID- 2574494 TI - Transmembrane signaling via both CD3 and CD2 human T cell surface molecules involves protein kinase-C translocation. AB - The activation of T lymphocytes by appropriate pairs of anti-CD2 monoclonal antibodies has been shown to involve phospholipase-C and phosphoinositide hydrolysis. In this paper we show that the stimulation of the human cloned leukemic T cell line Jurkat by anti-CD2 as well as anti-CD3 monoclonal antibodies induces translocation from cytosol to cell membrane of protein kinase-C (PKC), which is dependent on the formation of 1,2-diacylglycerol from inositol 4,5 diphosphate. PKC translocation is rapid and transient: the kinetics of enzyme redistribution are similar for CD2 and CD3. These results further stress that CD2 and CD3 T cell activation pathways use similar signal transducing mechanisms. PMID- 2574496 TI - The importance of potassium and lactate for maximal exercise performance during beta blockade. AB - Changes in femoral vein pH, lactate, glucose and potassium were studied in a double-blind randomized, short-term, dynamic cycle ergometry exercise test on six healthy male subjects after administration of non-selective (timolol), beta-1 selective (atenolol) beta blocker or placebo. The exercise intensity was increased in steps of 200 kpm/min every 2 min until exhaustion. During submaximal exercise, potassium concentrations in blood from the exercising leg muscles increased progressively with increasing exercise intensity, and was significantly higher for any given exercise level following timolol as compared to placebo administration. The potassium concentrations following atenolol were in-between those of timolol and placebo. Despite reduced working capacity after non selective beta blockade, almost identical potassium concentrations were reached at exhaustion irrespective of treatment regimens (placebo: 6.3, range 5.8-6.8 mmol/l; atenolol: 6.5, range 6.1-7.3 mmol/l and timolol: 6.4, range 6.2-6.8 mmol/l). The increase in s-lactate concentrations was similar across all treatments, and rose in proportion to the increase in the exercise intensity. A biphasic increase in lactate was observed with identical breaking points (anaerobic threshold) irrespective of treatment regimens. There was no difference in glucose concentrations between the treatment regimens. The marked increase in serum potassium during maximal exercise coincides with leg muscle fatigue and may, by its effect on the muscle cell membrane potential, limit the maximal working capacity following beta blockers. The rise in serum potassium may curtail the use of maximal exercise test as an index of cardiac performance in healthy young subjects. PMID- 2574497 TI - Spinovagal reflex modulation of gastric motility in response to mucosal nociceptive stimulation in the anaesthetized rat. AB - In anesthetized rats treated with guanethidine, the pylorus was ligated. A catheter was inserted into the stomach via the mouth and anchored by a ligature around the cervical oesophagus. The catheter was used for instillation into the stomach of a fixed volume (9 ml) of either isotonic or 1 M NaCl and for the recording of intragastric pressure. Neurogenic modulation of gastric motility caused by either solution was analysed by studying the effect of the systemic administration of the ganglionic blocker hexamethonium on gastric tone and on phasic motor activity. Gastric motility was not significantly changed by hexamethonium in the animals that had been subjected to isotonic NaCl. After intragastric treatment with 1 M NaCl, however, hexamethonium caused increased gastric tone and decreased phasic motor activity. An analysis of these results suggests that 1 M NaCl activated vagal non-adrenergic, non-cholinergic relaxatory and cholinergic excitatory motor neurons, respectively. These chemically induced modulations of gastric motility were dependent on the spinal cord and, most probably, were due to activation of the mucosal sensory endings of the splanchnic nerves, leading to reflex spinovagal motor adjustments. PMID- 2574498 TI - Dual effects of intracerebroventricularly applied nicotine on gastric motility in rats. AB - Intracerebroventricularly (i. c. v.) administered nicotine induced a decrease followed by an increase in gastric motility in urethane-anesthetized rats. These effects of i. c. v. administered nicotine were antagonized by simultaneously i. c. v. administered hexamethonium. Both vagotomy and pretreatment with atropine abolished the increasing effect of i. c. v. administered nicotine. In vagotomized rats, i. c. v. administered nicotine did not cause any decrease in gastric motility after elevation by electrical stimulation of the vagus nerve. These results suggest that i. c. v. administered nicotine activates central nicotinic receptors and that the vagus nerve is involved in both the inhibitory and stimulatory effects of i. c. v. administered nicotine on gastric motility. PMID- 2574499 TI - Tumor suppressor genes: the puzzle and the promise. AB - Tumor suppressor genes are wild-type alleles of genes that play regulatory roles in cell proliferation, differentiation, and other cellular and systemic processes. It is their loss or inactivation that is oncogenic. The first evidence of tumor suppressor genes appeared in the early 1970s, but only within the past few years has a wealth of new information illuminated the central importance of these genes. Two or more different suppressor genes may be inactivated in the same tumors, and the same suppressors may be inactive in different tumor types (for example, lung, breast, and colon). The suppressor genes already identified are involved in cell cycle control, signal transduction, angiogenesis, and development, indicating that they contribute to a broad array of normal and tumor related functions. It is proposed that tumor suppressor genes provide a vast untapped resource for anticancer therapy. PMID- 2574500 TI - Chromosome localization and cDNA sequence of murine and human genes for ras p21 GTPase activating protein (GAP). AB - The cDNA coding for mouse and human ras p21 GTPase-activating protein (GAP) was isolated; the deduced amino acid sequences share over 96% homology with that previously determined for bovine brain GAP. Both the mouse and human GAP cDNAs were used as probes for the chromosomal localization of this gene. The locus designations for the gene encoding GAP in human and mouse are RASA and Rasa (for ras-activating protein), respectively. By somatic cell hybrid analysis and in situ chromosomal hybridization, we have assigned the RASA gene to human chromosome band 5q13.3. In addition, with somatic cell genetics and linkage analysis in recombinant inbred mouse strains, the murine Rasa gene was localized to the distal end of mouse chromosome 13. These assignments place the gene encoding GAP in a known conserved syntenic region. PMID- 2574501 TI - Localization of fructose 6-P,2-kinase: fructose 2,6-bisphosphatase to human chromosome X. AB - The gene encoding human liver fructose 6-P,2-kinase: fructose 2,6-bisphosphatase has been assigned to human chromosome X by Southern analysis of a panel of human rodent somatic cell hybrid DNAs with a cDNA for this gene. A simple two-allele restriction fragment length polymorphism was found with the Fru-6-P,2-kinase:Fru 2,6-bisphosphatase probe; this will allow further localization of this gene by genetic linkage analysis. PMID- 2574502 TI - [Double-blind versus placebo comparison of single dose alpidem (50 mg or 75 mg) in a model of situational anxiety]. AB - Alpidem (Ananxyl) is a new imidazopyridine anxiolytic. Two studies of single doses of alpidem (50 or 75 mg) versus placebo, involving 104 patients each, showed alpidem at these two doses to be effective in a human model for situational anxiety, which is the psychological state of patients awaiting cardiovascular examination or surgery. Clinical assessment showed no significant difference in safety between alpidem 50 mg and placebo. Conversely, at the dose of 75 mg, there was a higher incidence of drowsiness with alpidem than with placebo. PMID- 2574503 TI - [Acute encephalopathy during lithium-neuroleptic combined treatment]. PMID- 2574504 TI - [Gene technology and mental disorders]. AB - The article briefly reviews the use of modern molecular genetic methods in research into the genetic bases of psychiatric diseases. It raises some basic methodological problems, and describes more recent technologies (RFLP/VNTR markers). Present knowledge about the molecular genetics of Alzheimer's disease, schizophrenia, manic depression, Tourette's syndrome and infantile autism is briefly reviewed in to order show the potential benefits of gene technological methods in this area of research. PMID- 2574505 TI - [Use of modern gene technology in forensic medicine]. AB - Modern DNA technology has had a great impact upon the practice of forensic genetics. Recently developed methods have disclosed different types of genetic variability in human DNA. Typing of genetic DNA polymorphisms based on point mutations represents an alternative to the blood and protein systems developed before. However, the discovery of the so-called hypervariable regions (HVR) in the genome, which represent grossly rearranged areas of DNA, has, revolutionised the field. "Fingerprints", nearly specific for each individual in the population, can be developed by employing specific probes, restriction enzymes and Southern blot technique. We present some results of the application of these techniques in criminal cases investigated at the Institute of Forensic Medicine in Oslo. In future, the sensitivity of the methods may be increased through amplification procedures (PCR reaction). PMID- 2574506 TI - RFLP analysis of DLA class I genes in the dog. AB - Human major histocompatibility complex (HLA) cDNA probes for class I genes HLA A,B and HLA-E were used to analyze the Restriction Fragment Length Polymorphism (RFLP) of the class I region of the canine major histocompatibility complex (DLA) in 40 dogs. The Southern blot analysis demonstrated that the dog genome contains at least eight class I genes, including the canine homologues of HLA-A,B and HLA E genes. The DNA polymorphism detected by the HLA-B7 probe corresponded to the serologically defined DLA-A allelic series. Restriction fragments that correlated with the DLA-A2, -A7 and -A9 antigenic specificities were identified in PstI digests of genomic DNA. The RFLP analysis was particularly useful in genotyping dogs which were not clearly DLA-A typable by serology. This technique can be used as a supplement to serotyping and as a genotyping tool for DLA antigenic specificities for which specific antisera are not available. PMID- 2574507 TI - In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. V. Evidence that humoral immune response to monoclonal antibodies and immunotoxin conjugates abrogates their cytotoxic activity. AB - Monoclonal antibodies, either alone or conjugated to toxins, hold promise as important therapeutic agents. However, the immune response to these foreign protein agents may markedly limit their therapeutic utility in vivo. We have administered both an interleukin-2 receptor-specific monoclonal antibody (anti-IL 2R) and a CD2-specific monoclonal antibody linked to the ribosome-inactivating protein gelonin to macaque monkeys. The monkeys developed high-titer antibody responses to mouse Ig and, when immunotoxin was administered, to the toxin gelonin. Their antimouse Ig antibody responses were broadly reactive with mouse Ig of differing idiotypes and isotypes. Furthermore, sera from these monkeys blocked the in vitro cytotoxic effect of anti-IL-2R or immunotoxin. This blocking was mediated by both the antimouse Ig and the antigelonin antibodies. Serum from a monkey infused with one CD2-specific monoclonal antibody blocked the in vitro cytotoxicity of two other isotypically different CD2-specific monoclonal antibody conjugates. In addition, this serum blocked the in vitro cytotoxicity of a gelonin-monoclonal antibody conjugate of an unrelated specificity. These data indicate that the immune response to some monoclonal antibodies and toxins might preclude the later use of this class of substances in an individual. Therefore, strategies for the parental therapeutic use of monoclonal antibodies and immunotoxins must take into consideration the possible limiting effects of the humoral immune response to these agents. PMID- 2574508 TI - Dopaminergic drug-receptor interactions. PMID- 2574509 TI - The antiarrhythmic properties of beta-adrenoceptor antagonists. AB - The antiarrhythmic properties of beta-adrenoceptor antagonists have long been recognized and, according to the Vaughan Williams classification of antiarrhythmic drugs, these drugs are regarded as a separate entity, namely class II. In this review, Ad IJzerman and Willem Soudijn focus on the nature and the molecular basis of the antiarrhythmic action of beta-adrenoceptor antagonists. Structure-activity relationship studies demonstrate that the antiarrhythmic profile of different beta-adrenoceptor antagonists is not fixed and some compounds have class I or class III properties which may be clinically relevant. PMID- 2574510 TI - Control of transmitter release from the motor nerve by presynaptic nicotinic and muscarinic autoreceptors. AB - Until recently, release studies have failed to indicate the existence of autoreceptors on motor nerves. Ignaz Wessler now reports on a refinement of the technique - the measurement of newly synthesized [3H]acetylcholine released from the phrenic nerve - which provides clear evidence in support of release modulating autoreceptors. Presynaptic nicotinic receptors mediate a positive feedback mechanism, can rapidly be desensitized and appear to differ in their pharmacological profile from the postsynaptic receptors. In addition, inhibitory and facilitatory muscarinic receptors appear to be involved in the presynaptic control of transmitter release from the phrenic nerve. PMID- 2574511 TI - Mosquito transmission of hepatitis B. PMID- 2574512 TI - [Sulfasalazin--enteric-coated tablets or common tablets?]. PMID- 2574513 TI - Cellular events in alveolitis and the evolution of pulmonary fibrosis. AB - "Alveolitis", as opposed to "pneumonia" sensu strictiori, is a term used to denote diffuse inflammatory changes of the pulmonary parenchyma, excluding those that result from local bacterial, fungal or other extracellular microbial growth. The various types of alveolitis are classified according to their histological characteristics and range from "luminal phagocytic" or "mural lymphoplasmacellular" and "exudative" to "fibrosing" alveolitis. In this overview, various exogenous and endogenous causes of different types of alveolitis, and the cellular events in their pathogenesis are briefly discussed to illustrate the complex mechanisms involved. Particular emphasis is placed on the possible transition from diffuse exudative to fibrosing alveolitis. It appears that pulmonary fibrosis, which is usually patchy rather than truly diffuse, does not have a uniform pathogenesis. Besides the possibility of a certain degree of a diffuse fibrosis three major pathways are evident: (1) granulation tissue budding into alveolar lumina (luminal fibrosis) (2) exudate incorporation into alveolar walls (mural fibrosis) and--at least equally important--(3) so-called collapse (atelectatic) induration (obliterative interseptal fibrosis), a process that has largely been neglected so far. PMID- 2574514 TI - Freeze-fracture investigation of the red pulp of human spleen. AB - This study concerns the morphology of the human spleen in freeze-fracture replicas and compares this with the findings in ultrathin sections. The material investigated consisted of two spleens resected at gastrectomy and one resected because of splenomegaly in a case of hairy cell leukaemia. The current concepts concerning the ultrastructure of the spleen were generally confirmed with the freeze-fracture technique. The sinus walls were found, as expected, to consist of closely fitting endothelial cells, which were identifiable in freeze-fracture replicas by numerous caveolae of the cell membrane. Contrary to the opinion upheld in the literature, the sinus endothelial cells were occasionally found to be connected by desmosomes or maculae adhaerentes. Corresponding to the finding of desmosomes in ultrathin sections, focal collections of intramembranous particles were observed in freeze-fracture replicas and a positive immunohistochemical reaction for desmoplakin in the sinuses was found at the light microscopic level. The view generally held in the literature that sinus endothelial cells can exhibit tight junctions was not confirmed. However, such junctions were found between vascular endothelial cells. The ring fibres of the sinuses, which are closely connected to the sinus endothelial cells through contractile fibres, apparently have various functions. Firstly, they contribute towards maintaining mechanical stability. Secondly, they represent basement membranes through which exchange occurs between the sinus endothelial cells and their surroundings. This is indicated by the caveolae and vesicles that are often found here in large numbers and in focal collections. Hairy cells exhibit no features in freeze-fracture replicas to suggest a cytogenetic relationship to interdigitating reticulum cells. PMID- 2574516 TI - Immunohistochemical and biochemical studies on the collagenous proteins of human osteosarcomas. AB - The distribution of type I, II, III, IV, V and VI collagens in 20 cases of osteosarcoma was demonstrated immunohistochemically using monospecific antibodies to different collagen types. In addition, biochemical analysis was made on collagenous proteins synthesized by tumor cells in short-term cultures obtained from seven representative cases and compared with dermal fibroblasts. In osteoblastic areas, most of the tumor osteoid consisted exclusively of type I collagen. Type V collagen was associated in some of them. Type III and type VI collagens were mainly localized in the perivascular fibrous stroma. Cultured tumor cells from osteoblastic osteosarcomas produced type I collagen exclusively and small amount of type V collagen constantly, while the synthetic activity of type III collagen was extremely low. In contrast, fibroblastic areas were characterized by the codistribution of type I, III, VI collagens and chondroblastic areas by type I, V, VI collagens as well as type II. Furthermore, type IV collagen was demonstrated in the stroma, other than the basement membrane region of blood vessels, in fibroblastic, intramedullary well-differentiated and telangiectatic osteosarcomas. In vitro, the production of variable amounts of type IV collagen, which was not detected in cultured dermal fibroblasts, was also recognized in the osteoblastic, fibroblastic, undifferentiated and intramedullary well-differentiated osteosarcomas examined. These findings suggest that the immunohistochemical approach using monospecific antibodies to different collagen types is useful not only in identifying some specific organoid components, such as tumor osteoid, but also in disclosing the biological properties of osteosarcoma cells with diverse differentiation. PMID- 2574515 TI - Stimulant effect of the immunomodulator MTP-PE on proliferation of monocytic cells in the guinea pig. AB - The effect of a single subcutaneous injection of various doses of the lipophilic muramyl tripeptide MTP-PE on cell proliferation was investigated in autoradiographs of histological sections of various organs of the guinea pig. The animals either received first MTP-PE in saline and then one 3H-thymidine pulse 1 h prior to sacrifice, or they were prelabeled with 3H-thymidine and then received MTP-PE. The number of proliferating cells increased up to between two and fivefold (marginally after 0.3 mg/kg and maximally after 30 mg/kg MTP-PE), but differed in the various organs. In addition, the time of the maximal increase varied between 5 h and 72 h after MTP-PE treatment and also depended on the organ. The majority of proliferating cells were of the monocyte lineage seen in conjunction with the vascular system. They were apparently promonocytes still capable of proliferation. Evidence for this conclusion is derived from (i) the distribution of 1 h-pulse-labeled cells in the various organ compartments in relation to the stimulated proliferation of the bone-marrow cells, and (ii) the distribution of the prelabeled, mainly bone-marrow derived cells, to the various organs. The augmented proliferation of the monocyte lineage is preceded by a dose dependent, short-lasting increase in the proliferation of some epithelia and also by an increase in body temperature and a transient change in plasma proteins. These effects are part of a limited inflammatory reaction and may contribute to the immunostimulation. PMID- 2574517 TI - The fate of lipopolysaccharide in cultured rat Kupffer cells. AB - Cultured rat Kupffer cells were incubated in presence of biologically tritiated Salmonella abortus equi lipopolysaccharide. Uptake of lipopolysaccharide increased rapidly during the first 2 h of incubation and then levelled off. Within the first h of incubation 10(6) Kupffer cells were able to ingest up to 18 micrograms lipopolysaccharide. Kupffer cells metabolised lipopolysaccharide and released lipopolysaccharide-related substances, but neither the cell-associated lipopolysaccharide nor the released lipopolysaccharide products were detoxified, as measured by the mouse lethality test. PMID- 2574518 TI - Inhibition of human immunodeficiency virus (HIV-1) infection by diphenylhydantoin (dilantin) implicates role of cellular calcium in virus life cycle. AB - Details of the molecular interactions between human immunodeficiency virus (HIV 1) and its host cell during the infection process are not entirely clear. Building on recent reports by Lehr and Zimmer (1986, DMW 111, 1001-1002) that the membrane-reactive, anti-epileptic drug diphenylhydantoin (dilantin or phenytoin) (PHT) inhibited binding of HIV to lymphocytes, we hypothesized that understanding the relevant effects of this drug on cells may shed light on aspects of HIV-1 infection. We found that PHT inhibited, in a dose-dependent manner, de novo infection of various T-cell lines as well as a monocytic cell line. Moderate inhibition of HIV-1 infection was observed with drug concentrations that are therapeutic in vivo for epilepsy (approximately 20 micrograms/ml), and no concentrations used induced deleterious effects on cell growth or viability. Surprisingly, treatment of chronically infected H9 cells reduced HIV p24 expression within 1-6 weeks according to dose. This apparent induction into latency was not inhibited by cotreatment of the chronically infected cells with 5 azacytidine, which indicated that PHT was not inducing latency by induction of methylation of the viral DNA. Flow cytometric analysis demonstrated that PHT did not significantly reduce cell-surface expression of CD4. The possibility remained that the drug inhibited HIV infection due to its known effects on calcium dependent cellular processes. Subsequent measurements of intracellular calcium demonstrated that an increase of [Ca2+]i occurred at least 24 hr postinfection, prior to synthesis of detectable viral structural protein p24, and that this virus-induced increase in [Ca2+]i was not due to binding of HIV to the cell. This HIV-induced rise in [Ca2+]i was significantly inhibited by PHT. PHT demonstrated variable inhibitory effects on infection of normal PHA-stimulated PBLs cultured in vitro, but it was synergistic to low-dose AZT (0.01 microgram/ml) in inhibiting infection of cell lines. Because of the known inhibitory effects of PHT on calcium-dependent biochemical processes in the cell, inhibition of HIV-1 infection by PHT suggests that calcium may play a role in HIV infection and maintenance. The drug may also be a candidate therapy for individuals infected with HIV. PMID- 2574519 TI - [The advisability of using antihistamine preparations and their therapeutic efficacy]. PMID- 2574520 TI - [Current concepts of the mediators of the vasomotor nerves and their role in regulating vascular tonus]. PMID- 2574522 TI - Isolated necrotizing panarteritis of the gallbladder. Case report. AB - Two cases of isolated gallbladder involvement by necrotizing panarteritis histologically resembling classic polyarteritis nodosa are reported and the literature is reviewed. No reports suggest that isolated gallbladder involvement may evolve to systemic ('classic') polyarteritis nodosa. Finding of necrotizing panarteritis in the gallbladder without clinical evidence of systemic/multiorgan disease does not warrant extensive investigations. PMID- 2574521 TI - Long-term follow up of patients with Zollinger-Ellison syndrome (ZES). AB - We have followed 14 patients with the Zollinger-Ellison syndrome for a median period of 9 years. All patients have suffered from peptic ulcer disease and six of the 14 have had complications such as bleeding or perforated ulcer. Almost half the patients have had diarrhoea as a dominant symptom and 4 patients suffered from multiple endocrine neoplasia. Before 1978, the year when the H2 receptor antagonists were introduced, the majority of the patients were operated with total gastrectomy. After that year there has been no need for gastrectomies, but all but two patients have undergone an explorative laparotomy. We have been able to localize the gastrinoma in 9 of 12 operated patients; in 7 cases it was localized within the gastrinoma triangle. Three of the patients are considered to have been cured after surgery. Eight patients have needed adjuvant acid-reducing medical therapy. Five of these have been failures to high doses of H2-receptor antagonists and have been successfully treated with omeprazole. Five patients have died during the follow-up period and death in two of these cases was related to tumor progression. PMID- 2574523 TI - Outpatient orchiopexy and herniotomy in children. AB - In 497 children with 528 hernia and 190 boys with 241 maldescended tests, outpatient operation was performed in 96.5% and 92.6% of the patients with an immediate surgical complication rate of 1.5% and 0% respectively. No wound infection was observed and the long term result was satisfactory with 3.7% hernia recurrences and 90% of the tests localized in the bottom of scrotum. Orchiopexy at about two years of age and early herniotomy, irrespective of age, is recommended and surgery may safely be carried out on an outpatient basis. PMID- 2574524 TI - The cytoprotective effect of the desamino-D-Trp 7-10 fragment of somatostatin on ethanol-induced erosions in the rat stomach. AB - The concept of cytoprotection was established by Robert. It means that several materials of different structure and in doses which are not antisecretoric ones, can protect the gastric mucosa against exogenous noxous agents. Absolute ethanol causes haemorrhagic erosions on the rat gastric mucosa. Somatostatin (SRIF) and its 7-10 fragment, which is the active centre of the hormone were cytoprotective in the ethanol-induced cytoprotective model. The desamino-D-Trp fragment (a suspected enzyme resistant variant of the active centre of SRIF) is also protective. It decreases significantly the extension of the lesions. Its dose response curve shows two peaks, which may correspond to the existence of two SRIF receptor types, described in the rat gastric mucosa. PMID- 2574525 TI - Quantitation by computerized visual image analysis of gastric mucosal lesions induced in mice and rats by non-steroidal anti-inflammatory drugs. AB - A method is described for the quantative determination of gastric mucosal lesions induced by non-steroidal anti-inflammatory drugs in mice and rats. The area and number of gastric lesions present in formalin-fixed, glycerol-cleared mucosa is determined by computerized visual image analysis using instrumentation as described. The method is also applied to the determination of the protective effects of anti-ulcer agents (e.g. prostaglandin E2, pirenzepine). Thus this method affords unambiguous sensitive and determination of the percentage area of the mucosa damaged and the number of the lesions. PMID- 2574526 TI - Interaction between sympathetic nerve fibres and epithelial transport in the rat jejunal mucosa in vivo. AB - The aim of this study was to elucidate the mechanisms behind the absorptive response to mesenteric nerve stimulation (MNS). Segments of rat jejunum were mounted with intact blood circulation in an 'in-vivo chamber', allowing parallel registration of net fluid transport rate (NFT) and electrical parameters of the tissue. All segments secreted fluid spontaneously, and the secretion rate was inversely correlated to the corresponding potential difference (PD) across the segment. The secretion was not inhibited by atropine. The nicotinic antagonist hexamethonium (Hx) inhibited the secretion and changed the relationship between PD and NFT. MNS reversed the secretion into an absorption (absorptive response) and decreased PD and short-circuit current (SCC) (electrogenic response). Total tissue resistance (Rt) was not significantly changed. The absorptive response increased at high control secretion rates and the electrogenic response increased at high control PD levels. The electrogenic response was inversely related to the absorptive response; however, the presence of Hx reversed this correlation. Guanethidine, a sympatholytic agent, eliminated all effects of MNS. Phentolamine eliminated the absorptive response but not the electrogenic response, and the remaining electrogenic response was not sensitive to propranolol (a beta adrenergic antagonist). Hx induced similar but smaller effects than MNS, and after Hx treatment the MNS effects were reduced. We conclude: (1) Fluid secretion in our model involves a mechanism other than electrogenic Cl- secretion. (2) MNS activates sympathetic nerve fibres, which enhance fluid absorption and decrease PD and SCC. (3) The absorptive and electrogenic responses involve partly separate transport mechanisms. (4) Both responses are partly due to the inhibition of intramural secretory nervous pathways. (5) Some sympathetic nerve fibres interact directly with the epithelium. PMID- 2574527 TI - Effects of pre-junctional alpha-receptor blockade on vascular neuro-effector characteristics in rats on high sodium intake. AB - Various in-vitro studies have indicated a direct attenuating effect of sodium on the affinity of adrenergic alpha 2-receptors. It has been suggested that ingested sodium in this way might increase blood pressure by reducing the activity of central alpha 2-receptors and thereby increasing sympathetic discharge. However, such an effect of sodium would also impair the function of peripheral alpha 2 receptors. In the present study we have therefore investigated the effect of high sodium intake on the alpha 2-receptor-mediated inhibition of the vascular neurogenic response. Male Wistar rats were given 2% NaCl in their drinking water from 4 to 9 weeks of age. Another group receiving plain tap water served as controls. Segments of small branches from the mesenteric artery were mounted in a myograph. Responses to transmural nerve stimulation were determined before and after alpha 2-receptor blockade with either yohimbine or idazoxan. The response to a continuous nerve stimulation that elicited 30% of maximal contraction was increased 2-3 times after addition of either idazoxan (0.1 microM) or yohimbine (0.3 microM), with no significant difference between sodium-treated and control rats; if anything the enhancement was slightly greater in the sodium-treated group. Also, responses to intermittent burst stimulation were increased from 30 to about 80% of maximal response in both rat groups. The results thus indicate that high sodium intake does not affect the inhibitory influence of pre junctional alpha 2-receptors on the vascular neurogenic response. PMID- 2574528 TI - Does routine screening for benzodiazepines help to diagnose dependence in psychiatric inpatients? AB - After admission, 899 inpatients of a psychiatric university hospital were routinely screened for benzodiazepines (BDZ) in the urine. BDZ were detected in 134 (15%) patients with various primary diagnoses. Criteria for BDZ abuse or dependence were found in 36 patients. In 35 cases, either intake of BDZ had not been reported in the first psychiatric interview, or such a report had not been documented in the patient's charts. None of these 35 patients was found to have BDZ abuse or dependence. Psychiatric inpatients with BDZ abuse or dependence seem to report their intake of BDZ. These findings suggest that a routine screening for BDZ can hardly help to diagnose dependence within a university hospital setting. Nevertheless, an objective test for intake of BDZ may be useful in special cases. PMID- 2574529 TI - Effect of clonazepam on neuroleptic-induced oculogyric crisis. AB - Fourteen patients with neuroleptic-induced oculogyric crisis resistant to antiparkinsonian drugs were treated with oral clonazepam. The neuroleptic-induced oculogyric crisis was completely inhibited by clonazepam in 10 patients, moderately inhibited in 2, slightly inhibited in 1, and not changed in 1. We suggest that clonazepam is useful in managing neuroleptic-induced oculogyric crisis. PMID- 2574530 TI - Relationship between dexamethasone nonsuppression and negative symptoms in schizophrenic patients. PMID- 2574531 TI - Are there differences in the dependence potential of benzodiazepines? PMID- 2574533 TI - Restriction fragment length polymorphisms of the insulin receptor gene in families with insulin resistance and leprechaunism. AB - Restriction fragment length polymorphisms (RFLPs) for the insulin receptor gene were compared among controls and families Atl and Ark-1, whose probands have extreme insulin resistance and leprechaunism. Previous studies indicated that fibroblasts cultured from patients Atl and Ark-1 had less than 10% of normal insulin binding. Cells cultured from the related parents of Atl had partial reduction in insulin binding, suggesting that patient Atl inherited the same mutant allele for the insulin receptor from both his parents. By contrast, the parents of Ark-1 were unrelated and their cells had different degrees of impaired insulin binding, suggesting that patient Ark-1 inherited two different, non complementing alleles for the insulin receptor. To test these hypotheses, RFLPs were defined for the insulin receptor gene and their transmission was studied in families Atl and Ark-1. Patients affected with leprechaunism had no private polymorphisms in the insulin receptor gene, indicating that gross rearrangements were not present. A polymorphism generated with EcoRI at the 5' end of the insulin receptor gene gave fragments of 16 and 20 kb and was the only one informative in family Atl. Both parents were heterozygous, presenting a 16 and a 20 kb fragment, and transmitted the 20 kb allele to their affected offspring. Ark 1's parents were heterozygous for three different RFLPs, including this EcoRI polymorphism, and patient Ark-1 inherited a different allele for the insulin receptor from each parent. These results support the genetic hypotheses suggested by insulin-binding studies and indicate that RFLPs can be used to identify transmission of the insulin receptor gene in families with insulin resistance. PMID- 2574534 TI - Occurrence of male phenotype in genotypic females with congenital virilizing adrenal hyperplasia. AB - We report on two genotypic females with complete masculinization of the external genitalia secondary to congenital adrenal hyperplasia resulting from 21 hydroxylase deficiency. One patient had the salt-losing variant, and the other had the simple virilizing or nonsalt-losing variant. One was evaluated neonatally during an adrenal crisis and misidentified as male; the second was unrecognized. Both were being reared as males when the true genotype was recognized during evaluation for cryptorchidism. The female internal genitalia were subsequently removed and testicular implants placed. These cases demonstrate the need to exclude congenital virilizing adrenal hyperplasia in any phenotypic male infant with bilateral cryptorchidism. When this condition is diagnosed, early and genotypically appropriate sex assignment is important if reproductive function is to be preserved and subsequent emotional and social complications avoided. PMID- 2574532 TI - The effect of leukotriene antagonists, lipoxygenase inhibitors and selected standards on leukotriene-mediated allergic bronchospasm in guinea pigs. AB - Leukotrienes (LT) C4, D4, and E4 are major contributors to the pathobiology of human bronchial asthma. Therefore, it is likely that compounds that antagonize the action or inhibit the formation of LTs will be useful therapeutic agents. We have studied the effects of LT antagonists, 5-lipoxygenase inhibitors and selected standards in a model of LT-mediated allergic bronchospasm in guinea pigs. Sensitized animals were pretreated with mepyramine, indomethacin and propranolol to eliminate the influence of histamine, prostaglandins, thromboxanes and circulating catecholamines. In these animals, inhalation of antigen resulted in a bronchospasm consistent with a LT-mediated response that was slow in onset, of long duration and was inhibited by the selective LTD4, antagonists FPL-55712, LY-171,883 and ICI-198,615. ICI-198,615 was approximately 50-times more potent than FPL-55712 by the intravenous and intratracheal routes. However, of thirteen compounds known to inhibit 5-lipoxygenase and LT biosynthesis in vitro only phenidone, piriprost and AA-861 were active in this in vivo model. The allergic bronchospasm was inhibited by bronchodilators (e.g. PGE2, aminophylline and forskolin) and by some mast cell stabilizers, but was otherwise insensitive to other pharmacological classes of compounds including calcium channel blockers and antagonists of serotonin, acetylcholine and platelet-activating factor. This model seems useful and reasonably selective for the evaluation of new antianaphylactic compounds that are LT antagonists. The inactivity of many 5 lipoxygenase inhibitors in this model suggests they do not inhibit LT formation in vivo. PMID- 2574535 TI - Prenatal diagnosis of Friedreich ataxia. AB - Friedreich ataxia is a progressive neurodegenerative disorder affecting the peripheral and central nervous systems. One in 50,000 of the population are affected by this recessively inherited disorder, with onset usually before puberty. The recent localization of the disease locus to chromosome 9 has made it possible to provide genetic counselling to families with at least one affected child. Tight linkage of the disease mutation to an anonymous DNA marker MCT112 (D9S15) has been shown with a pairwise lod score of 36.1 at 0 = 0. We report here the first prenatal diagnosis in Friedreich ataxia. Using MCT112 and the confidence interval approach, we have calculated risks for a fully informative family with one affected sib. PMID- 2574536 TI - Keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression precedes dermal T lymphocytic infiltration in allergic contact dermatitis (Rhus dermatitis). AB - The ability of small molecules such as urushiol, present as a wax on the poison ivy leaf surface, to cause allergic contact dermatitis (rhus dermatitis) has fascinated immunologists for decades. Current dogma suggests that these epicutaneously applied catechol-containing molecules serve as haptens to conjugate with larger proteins via reactive o-quinone intermediates. These complexes are then recognized as foreign antigens by the immune system and elicit a hypersensitivity reaction. Phorbol ester can directly induce cultured keratinocyte (KC) intercellular adhesion molecule-1 (ICAM-1) expression via a protein kinase C (PK-C)-dependent mechanism. As urushiol is also a known PK-C agonist, we asked if topical application of a poison ivy/oak mixture could directly induce epidermal KC ICAM-1 expression. During the pre-erythematous phase of this reaction (4 to 20 hours), epidermal KCs expressed ICAM-1; this "initiation phase" preceded the appearance of activated memory T lymphocytes in the papillary dermis, and thus appeared to be nonlymphokine mediated. A near contiguous cellular-adhesion molecular network was identified by ICAM-1 staining of basal KCs, dermal dendrocytes, and endothelial cells. During the second 24 hour period with the onset of erythema and edema, there was an "amplification phase" of more intense KC ICAM-1 expression coupled with relatively weak KC HLA DR expression that coincided with dermal and epidermal T-cell infiltration. This suggests the presence of lymphokines, such as gamma interferon, during the amplification phase because of KC HLA-DR expression. On cultured KCs, urushiol directly induced ICAM-1 expression but not HLA-DR. Thus, in addition to functioning as an antigenic hapten, urushiol directly induces KC ICAM-1 expression. The KC ICAM-1 expression may then alter the dynamic trafficking of memory T cells in the epidermis, so as to initiate cutaneous inflammation in a nonantigen specific manner. This initiation phase is followed by T-cell infiltration and consequent lymphokine production that significantly amplifies the original stimulus. Thus much can still be learned about the molecular pathophysiology of this common type of cutaneous inflammation. PMID- 2574537 TI - Anionic amino acid uptake by microvillous membrane vesicles from human placenta. AB - The transport mechanisms for anionic amino acids in trophoblast microvillous (maternal facing) membrane were investigated by characterization of L [3H]aspartate and L-[3H]glutamate uptake in membrane vesicles. Uptake of the anionic amino acids was by a single high-affinity Na+-dependent K+-stimulated cotransporter that is pH sensitive and electrogenic. A second Na+-dependent transporter could not be discriminated, and there was no observable Na+ independent uptake. An outwardly directed K+ gradient (100 mM KCl inside) resulted in a 5- to 10-fold stimulation in glutamate uptake in the presence of Na+. Intravesicular KCl had no effect on transporter affinity but increased transporter velocity in a concentration-dependent manner. Inhibition of Na+-K+ dependent uptake of L-aspartate and L-glutamate (20 mM, 30 s) by 2 mM unlabeled amino acids demonstrated stereoselectivity for L-glutamate but not for L aspartate. The neutral amino acids (L-alanine, L-threonine, L-serine, L-cysteine, L-phenylalanine) were not effective inhibitors. These data are consistent with an anionic amino acid transporter in the microvillous membrane of the trophoblast, which has characteristics qualitatively similar to the X-AG system found in other epithelia. This system may mediate the concentrative placental uptake of anionic amino acids from maternal blood in utero. PMID- 2574538 TI - Escape of hepatic glucose production during hyperglycemic clamp. AB - The role of the pattern of insulin secretion on hepatic glucose production (HGP) was evaluated with hyperglycemic and euglycemic clamp studies in six normal young nonobese subjects. In the hyperglycemic studies, glucose levels were raised and maintained at 98 mg/dl above basal for 150 min. Each subject responded with a biphasic pattern of immunoreactive insulin (IRI) release. HGP was completely suppressed by 20 min, coincident with the first-phase insulin release. HGP then rose steadily, surpassing the basal rate by 100 min when IRI had reached the peak levels of the first phase. By 130 min, when IRI had surpassed the peak first phase levels, HGP began to fall. In the euglycemic studies with a square wave of hyperinsulinemia (approximately 25 microU/ml), HGP was suppressed to approximately 60% of basal and remained at that rate. We next repeated the hyperglycemic studies with somatostatin, glucagon, and insulin infusions. In these studies with a square wave of hyperinsulinemia (approximately 40 microU/ml, the level observed during the first phase IRI of the previous hyperglycemic clamps), HGP was suppressed to approximately 43% of basal rate and remained at that rate. These studies indicate insulin regulation of HGP is not only dependent on insulin level but may be strongly influenced by the pattern, over time, of insulin secretion. PMID- 2574539 TI - Effects of various agents on ileal postprandial motor patterns and transit of chyme in dogs. AB - Effects of intravenous infusions of somatostatin, methionine-enkephalin, and 5 hydroxytryptophan on canine ileal motor patterns and transit of chyme were investigated postprandially. Motility was recorded by multiple closely spaced extraluminal strain gauges. By a computerized method, the length of contraction spread and other motility parameters were evaluated. Transit rates were measured fluoroscopically. Somatostatin and methionine-enkephalin initiated a mixing activity by reducing the incidence and the length of spread of contraction waves induced by a noncaloric meal. Methionine-enkephalin, but not somatostatin, decreased both the number of contractions per minute and the motility index. 5 Hydroxytryptophan converted the mixing activity induced by a nutrient meal into a propulsive pattern. The incidence and the length of spread of contraction waves as well as the number of contractions per minute, the contraction force, and the motility index were enhanced. Results suggest that somatostatin, methionine enkephalin, and 5-hydroxytryptophan are effective modulators of ileal propulsive activity. Effects are largely similar to those observed in the proximal jejunum, although the lengths of contraction spread and the transit rates were generally less in the ileum. PMID- 2574540 TI - Pressor responses in conscious rats with chronic portal venous hypertension. AB - Heart rate, mean arterial pressure (MAP), and vascular conductance responses to graded phenylephrine (PE) infusions were compared in conscious, unrestrained portal vein-stenosed (PS), and sham-operated (SO) rats chronically instrumented for pulsed Doppler flowmetry. Ten days after stenosis, MAP was lower in PS than in SO, and PS heart rates were higher. Pressor sensitivity to PE was attenuated 70%, and bradycardic responses to increases in MAP were 47% greater in PS. Abdominal aorta vascular bed conductance sensitivity was reduced 84%, and renal artery sensitivity was reduced 29% in PS compared with SO, whereas the superior mesenteric artery conductance response was unaffected by portal vein stenosis. After ganglionic blockade, the heart rate of PS remained greater than that of SO, and comparisons of renal artery, abdominal aorta, and superior mesenteric artery vascular conductances revealed no significant differences in neurogenic vascular tone. Differences between PS and SO pressor responses were abolished by ganglionic blockade, as were differences in vascular bed conductance responses. These findings suggest that a greater bradycardic response and greater baroreflex mediated withdrawal of sympathetic tone from skeletal muscle and renal vascular beds were responsible for the decreased pressor sensitivity observed in PS animals. PMID- 2574541 TI - [Protective effect of narcotic analgesics on the mother, fetus and offspring in hypoxia]. AB - The protective effect of the narcoanalgetics, viadril (hydroxydione sodium succinate) and administered intraperitoneally in doses of 5 and 20 mg/kg was studied in the experiment on 146 pregnant noninbred white rats with simulated hemic hypoxia in the late pregnancy (the 19th day). The aforementioned rats were studied for the composition of the peripheral blood, their weight gain oxidative isoenzymes (LDH), pH and pO2 in the blood. Wilson's technique was used for the assessment of the fetal status. The offspring was studied with regard to the weight increment, the rate of postnatal mortality, behavioral reactions, etc. It was stated that viadril strengthened the resistance of pregnant animals to hypoxia and contributed to the alleviation of late sequela of posthypoxic changes in the fetus and newborn. PMID- 2574542 TI - Evaluation of carbohydrate-deficient transferrin compared with Tf index and other markers of alcohol abuse. AB - It has been known for some years that a partial deglycosylation of transferrin occurs in the sera of alcohol abusers. Different methods have been proposed in order to evaluate this carbohydrate-deficient fraction of serum transferrin. Chromatofocusing or isoelectric focusing followed by direct immunofixation have been used until now. Recently, a new method called the carbohydrate-deficient transferrin (CDT) test based on ion-exchange chromatography has been developed by Stibler et al. (Alcohol Clin Exp Res 10:535-544, 1986). Here we compare this new method with results obtained using our Tf index determination method. The upper limit of normal values was set to the 90th percentile of the values observed in a reference population. The population under investigation consisted of 50 healthy volunteers and 160 alcohol abusers whose ethanol consumption was evaluated through a questionnaire. Sensitivity and specificity of the CDT test have been found higher than 0.76 and 0.90, respectively. The correlation between both methods was 0.794, a satisfactory result considering that the CDT test and the Tf index do not exactly measure the same part of the carbohydrate-deficient transferrin. In a population of 23 patients with liver diseases not related to alcohol abuse, no abnormal CDT value was observed. We can conclude from these results that the CDT test now seems to be the best test to detect alcohol abusers. PMID- 2574543 TI - Effects of alcohol ingestion on in vitro susceptibility of peripheral blood mononuclear cells to infection with HIV and of selected T-cell functions. AB - A role for the biological effects of alcohol is postulated in the increased risk of AIDS known to be associated with chronic alcohol abuse and alcohol consumption during sexual activity. In pilot experiments peripheral blood mononuclear cells from healthy volunteers were studied before and after a single ingestion of 0.7 to 3.1 liters of beer or an equivalent dose of ethanol in other beverages. After moderate alcohol consumption there was increased human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cells during 28 days of culture without mitogen stimulation as indicated by overnight syncytium formation with SUP-T1 indicator cells and by increased levels of HIV p24 antigen in the culture supernates. There was also decreased ability of lymphocytes to produce interleukin 2 and soluble immune response suppressor activity after stimulation with concanavalin A, the former, possibly both, for over 4 days after alcohol ingestion. These preliminary data extend well-known immunosuppressive effects of chronic alcohol ingestion to acute ingestion and raise the question: Could even casual alcohol consumption enhance HIV infectivity and/or enhance the progression of latent HIV infection? PMID- 2574544 TI - Dose-response studies of atracurium, vecuronium and pancuronium in the elderly. AB - Dose-response curves were constructed for atracurium, vecuronium and pancuronium in elderly subjects in order to assess potency of these relaxants. The results were compared to data previously obtained for adult subjects using the same method. A single-dose method of potency determination was used in both studies. The results indicate no significant difference in the potency of these relaxants between elderly and adult subjects; the ED95S were 249 and 226 micrograms/kg for atracurium, 43.1 and 39.6 micrograms/kg for vecuronium and 65.9 and 60 micrograms/kg for pancuronium respectively in the elderly and the adults. PMID- 2574545 TI - A comparison of the effects of suxamethonium, atracurium and vecuronium on intracranial haemodynamics in swine. AB - Sixteen Yorkshire swine weighing 15-20 kg were studied to compare the effects of suxamethonium, atracurium and vecuronium on intracranial pressure (ICP), heart rate (HR), arterial blood pressure (BP), and cerebral perfusion pressure (CPP) in swine with normal or elevated ICP. In each animal an intracranial pressure-volume curve was produced by the inflation of an epidural balloon. The baseline ICP (Po), the ICP at the inflection point (Pi) and on the steep portion (Pmax) of the pressure-volume curve were identified and the balloon volumes recorded. The animals were assigned to receive either suxamethonium 1.0 mg/kg, atracurium 0.6 mg/kg, vecuronium 0.2 mg/kg, or saline placebo intravenously at three conditions: First, with the epidural balloon deflated Po, next at Pi, then at Pmax. Neither atracurium, vecuronium, nor placebo produced any statistically significant effect on HR, BP, ICP, or CPP at any baseline level of ICP. Suxamethonium produced an early fall in ICP (0.8 +/- 0.3, 2.6 +/- 1.0 and 3.5 +/- 1.3 mmHg at Po, Pi and Pmax respectively: P = .0005) followed by a rapid rise above the pre-infusion level (1.8 +/- 0.6, 2.8 +/- 0.6 mmHg, and 2.2 +/- 0.5 mmHg at Po, Pi and Pmax respectively: P = .0005). A fall in BP coupled with the rise in ICP resulted in a fall in CPP (5.8 +/- 2.3, 6.1 +/- 1.2, and 6.3 +/- 1.8 mmHg at Po, Pi and Pmax respectively: P = .0005). Although the fall in CPP was not large, in the presence of elevated ICP, where CPP already is marginal, such a decrease may compromise cerebral blood flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574546 TI - Postoperative analgesia in neonates: an Australia-wide survey. AB - An Australia-wide survey of the use of postoperative analgesia in neonates has been conducted. A high overall use of analgesia has been recorded with 75% of respondents prescribing an opioid. The frequency of use of local or regional analgesia was disappointingly low at 8% overall. The general attitude is that analgesia is desirable but a fear of respiratory depression inhibits its use, particularly in non-ventilated neonates and after more minor surgery. It is suggested that a wider use of regional anaesthesia techniques may reduce this problem. PMID- 2574547 TI - Alpha coma and barbiturate poisoning. PMID- 2574548 TI - [The effect of preliminary administration of the beta-blocker inderal on the course of the postresuscitation period]. AB - The results of the effect of acute fetal blood loss and a beta-blocker inderal preinjection on the functional metabolic damage of vital organs in the early postresuscitation period are presented. It has been established that the drug preinjection restricts the lipolysis and considerably decreases the intensity of lipid peroxidation in the brain, heart and liver both due to prevention of antioxidant enzyme inhibition and to preservation of antioxidant lipid activity at a high level. It has been shown that inderal, retaining phospholipid content of cardiomyocyte membranes, reduces the electrical heart instability and completely prevents ventricular fibrillation in the early postresuscitation period. Inderal decreases considerably adenyl nucleotide brain and heart catabolism. PMID- 2574549 TI - Astemizole in perennial allergic rhinitis with seasonal exacerbations: a placebo controlled double-blind study. AB - Astemizole is a nonsedative H1-antagonist. It was used in a randomized double blind, placebo-controlled in-season trial to assess its efficacy in patients with perennial allergic rhinitis showing seasonal exacerbations. By the last (6th) week of the study, the mean overall symptomatology, as rated by a global composite score, was significantly mitigated in the astemizole-treated group (18 patients) compared with their first week's global composite score (P less than .01). No such improvement was observed in the placebo-treated group (18 patients). Side effects were not appreciable throughout this short-term study. We conclude that astemizole is effective in the treatment of patients with perennial allergic rhinitis showing seasonal enhancement of symptoms. PMID- 2574551 TI - Antihistamines in asthma. PMID- 2574550 TI - The effects of H1 antihistamines on the early allergic response. AB - To increase understanding of the effect of H1 antihistamines on the immediate response to nasal challenge with antigen, we performed two double blind, placebo controlled, crossover studies using cetirizine and terfenadine. The subjects underwent nasal challenge with antigen after premedication with either cetirizine (20 mg QD for two days, n = 10), terfenadine (60 mg BID for 1 week, n = 12), or placebo for equivalent periods of time. We monitored the response to challenge by counting the number of sneezes and by measuring the levels of inflammatory substances in recovered nasal lavages. Compared with placebo, both antihistamines significantly reduced sneezing and the levels of recovered albumin and TAME esterase activity, suggesting that both reduced the expected increase in vascular permeability. With cetirizine, there was also a reduction in the levels of LTC4 (not measured in terfenadine studies) but not in those of recovered histamine and prostaglandin D2. These data suggest that cetirizine did not affect mast cell mediator release, that histamine release is due to the direct action of antigen stimulation and that leukotrienes are generated by cells in addition to mast cells. With terfenadine, there were significant reductions in the levels of histamine and kinins (not measured in cetirizine study) seen after nasal challenge with antigen. The reduction in kinins most likely reflects alteration in vascular permeability, whereas the effect on histamine presumably reflects inhibition of mast cell activation. When combined, these experiments demonstrate effects of H1 antihistamines on histamine release beyond those usually described, as well as differences between drugs within a single classification. PMID- 2574552 TI - Central nervous system effects of antihistamines on evoked potentials. AB - Sedation is the most common side effect of antihistamine therapy. As with many behavioral constructs, attempts at quantification are difficult, and consequently, subjective reports of antihistamine sedation are frequently relied upon. Evoked potential activity is one method to quantitate the brain's response to subtle cognitive change. Evoked potentials are characteristic shifts in the brain's electrical activity that are obtained by time-locking the ongoing EEG to a stimulus over repeated trials. A late positive component of the evoked potential (P3) has been related to various psychologic properties including expectation, selective attention, and information processing speed. Because of this relationship, we employed the latency of the P3 evoked potential to measure the cognitive effects of chlorpheniramine and terfenadine. In healthy young subjects, we observed that terfenadine produces significantly less cognitive slowing of the P3 potential than chlorpheniramine. This finding supports the subjective findings of reduced sedative side effects of terfenadine. PMID- 2574553 TI - Evaluation of inhibition of wheal response to histamine by multiple doses of terfenadine. AB - The ability of drugs to inhibit histamine-induced wheals has been used frequently as a pharmacodynamic index of clinical efficacy. Host response using this model can be predictive of clinical response in atopic diseases such as allergic rhinitis and urticaria. Terfenadine is a widely used nonsedating antihistamine currently approved for use at a dosage of 60 mg every 12 hours. Our clinical trial was designed to determine whether higher dosages of this agent were associated with amplified efficacy in suppressing the wheal response to intradermal histamine phosphate. Twenty-six healthy male Caucasian volunteers were randomized in a double-blind crossover fashion to receive terfenadine 60 mg every 12 hours, 120 mg each day, 120 mg every 12 hours, and placebo. Each dose was given orally for three days followed by a 6-day washout period. Histamine was administered intradermally one hour prior to dosing for baseline measurements. Histamine was given at defined intervals after treatment or placebo on days 1 (acute dosing) and 3 (steady state), and the percent inhibition of histamine induced wheal area as compared with baseline was determined. Subjects receiving all three active doses exhibited significant wheal inhibition compared with placebo on days 1 and 3 (P less than or equal to .01). Subjects receiving the 60 mg every 12 hours and the 120 mg each day dosages exhibited roughly equivalent mean wheal suppression over the 24-hour period of each testing day (54% versus 60%, respectively, on day 1 and 62% versus 63%, respectively, on day 3, no significant differences).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574554 TI - Once versus twice daily dosing of terfenadine in the treatment of seasonal allergic rhinitis: US and European studies. AB - Terfenadine was compared for efficacy in treatment regimens of 120 mg once daily (qd) and 60 mg twice daily (bid) in patients with seasonal allergic rhinitis in double blind, randomized, parallel 1-week studies, three in Europe (one multicenter study, three sites; n = 191) and one in the US (single center; n = 201). Patients had moderate or severe symptoms for 2 or more years and positive skin tests to relevant pollen antigens. On entry and final visit individual symptoms were rated by physicians on a visual analog scale in Europe and a numerical scale in the US. Most patients filled out daily symptom diaries during the studies. Individual symptom scores and total symptom scores, (calculated by adding individual symptom scores together) as assessed by physicians and patients, were similar at baseline for both treatment regimens on entry, with improvement during the week. There were more patients with complete and marked relief in Europe than in the US. (Total symptom scores as assessed by physicians, for instance, improved from baseline ratings of 407 for the 60 bid regimen and 431 for the 120 qd regimen in Europe to 102 and 95 at final visit, and in the US from 8.8 for 60 bid and 8.5 for the 120 qd to 4.5 and 4.1). There was no statistical difference between the two treatment regimens in Europe or the US. Terfenadine, 120 mg once daily, is as effective as the currently approved dosage of 60 mg twice daily in the treatment of seasonal allergic rhinitis, and terfenadine, 120 mg once daily, has the added convenience of allowing the patient once a day dosing. PMID- 2574555 TI - Double-blind, placebo-controlled study of terfenadine and hydroxyzine in patients with chronic idiopathic urticaria. AB - Results of a double-blind, randomized, placebo-controlled, parallel study in 37 patients indicate that terfenadine, 60 mg bid, is significantly more effective than placebo and as effective as hydroxyzine, 25 mg qid, in the treatment of chronic idiopathic urticaria without causing the somnolence that was associated with the use of hydroxyzine. PMID- 2574556 TI - Tolerance to antihistamines: is it a problem? PMID- 2574557 TI - Treatment of external pancreatic fistulas with somatostatin. Second place winner: Conrad Jobst award. AB - Five patients with external pancreatic fistulas were treated with a synthetic peptide that mimics the action of somatostatin (Sandostatin, Sandoz; East Hanover, NJ). Four of the patients developed fistulas after drainage of pancreatic pseudocysts and one developed a fistula following resection of a pancreatic carcinoid. One day after initiation of therapy, the mean fistula output for the group decreased by 52 per cent. By three days, fistula output decreased by 70 per cent. All fistulas closed in 7 to 44 days. Adverse reactions to the drug included diarrhea in one patient and transient hyperglycemia in another. Sandostatin is effective in decreasing drainage from external pancreatic fistulas and may, therefore, facilitate their closure. No serious adverse reactions to the drug were noted. Further studies will better define the role of Sandostatin in the treatment of pancreatic fistulas. PMID- 2574558 TI - [Bone localization of carcinoid tumors]. PMID- 2574559 TI - [Biological monitoring of infection caused by human immunodeficiency virus (HIV)]. PMID- 2574560 TI - [Efficacy and tolerability of tertatolol in the treatment of mild to moderate arterial hypertension. Results of a French multicenter study with 2,338 patients treated over one year]. PMID- 2574562 TI - New acquisitions in the development of anti-HIV agents. PMID- 2574561 TI - Isozyme and DNA analysis of human S-adenosyl-L-homocysteine hydrolase (AHCY). AB - Erythrocyte and tissue isozymes of human AHCY have been studied by starch gel electrophoresis, cellulose acetate electrophoresis, isoelectric focusing and Na dodecyl sulphate electrophoresis. The same isozyme was observed in all the tissues studied, suggesting that human AHCY is encoded by a single structural locus. Two variant alleles were identified in erythrocyte AHCY using starch gel electrophoresis in a sample of 166 unrelated individuals from the British population. The gene frequencies were 0.024 for AHCY*2 and 0.006 for AHCY*3. The variant isozyme patterns could not be distinguished by isoelectric focusing. Using the homologous rat cDNA AHCY probe, human AHCY cDNA recombinants were isolated from a placental cDNA library. The human and rat sequences show considerable homology in the coding region of the gene and also, but to a lesser extent, in the distal part of the 3' untranslated region. Preliminary observations suggest the occurrence of a high frequency PvuII site RFLP identified with the human AHCY probe. PMID- 2574563 TI - Insulin-mediated regulation of tyrosine aminotransferase in rat hepatoma cells: inhibition of transcription and inhibition of enzyme degradation. AB - Insulin induces the enzyme tyrosine aminotransferase (TAT) in Reuber H-35 rat hepatoma cells. A clone of these cells (KRC-7) was used to study the relationship between changes in enzyme activity and hybridizable mRNA, and rates of transcription for TAT in response to insulin. Our results indicate that enzyme activity is inducible by insulin in the presence of an inhibitor of RNA synthesis, suggesting that insulin functions post-transcriptionally to increase enzyme activity. Unexpectedly, insulin causes a decrease in the level of hybridizable TAT mRNA. Glucocorticoids cause an increase in TAT mRNA and insulin inhibits this increase when added either subsequent to or simultaneous with the addition of this agonist. Transcriptional runoffs demonstrate that insulin inhibits transcription of TAT to account for the aforementioned decrease in hybridizable mRNA. To examine the possibility that a post-translational mechanism is responsible for the increase in TAT activity caused by insulin, the rate of degradation of TAT protein was measured using polyclonal antibody. These experiments indicate that the rate of degradation of TAT is decreased about twofold in the presence of insulin, which suggests that part of the observed increase in TAT activity is due to selective post-translational stabilization of TAT. Therefore, insulin regulates TAT in KRC-7 cells by both transcriptional and post-translational mechanisms, the latter being responsible for the increase in activity. PMID- 2574564 TI - Protein oxidation and proteolysis during aging and oxidative stress. AB - Previous studies in this laboratory have shown that glutamine synthetase (GS) and other key metabolic enzymes are inactivated by metal-catalyzed oxidation reactions in vitro. Oxidative inactivation renders these proteins highly susceptible to proteolysis, especially to a class of newly identified alkaline proteases which exhibit little or no activity against the native enzymes. These studies have suggested that oxidative inactivation may be an important marking step for intracellular protein degradation. Because many of the enzymes which have been shown to accumulate as inactive or less active forms during aging are readily inactivated by metal-catalyzed oxidation reactions in vitro, we have investigated the possible relationship between protein oxidation and proteolysis during aging and oxidative stress in vivo. Oxidized proteins accumulate in hepatocytes of rats exposed to 100% oxygen during the first 48 h of oxygen treatment. In the interval between 48 and 54 h the levels of oxidized proteins decline sharply. The specific activities of at least two liver enzymes, glutamine synthetase and glucose-6-phosphate dehydrogenase (G-6-PDH), decrease during the 54-h experiment. GS and G-6-PDH specific immunological cross-reactivity remains high during the first 48 h of oxygen treatment and then declines in the interval between 48 and 54 h. During this same interval the levels of alkaline proteases which degrade oxidized proteins increase, indicating that these activities are induced or activated in response to oxidative stress and subsequently degrade the proteins which have become oxidized during the initial phase of oxygen treatment. Oxidized proteins accumulate progressively during aging in hepatocytes from rats 3 to 26 months old, with the largest incremental increase between 20 and 26 months. The increase in protein oxidation is correlated with a loss of specific activity of GS and G-6-PDH without a concomitant loss of immunological cross reactivity. The levels of alkaline proteases which degrade oxidized proteins in hepatocytes from 26-month-old rats is only 20% that of 3-month-old rats, suggesting that oxidized proteins accumulate in hepatocytes from old rats, in part, because the proteases which degrade them are deficient or defective. moreover, when old rats are subjected to treatment with 100% oxygen, the levels of oxidized proteins continue to increase and the alkaline protease activity remains low, indicating that these protease activities are not increased in response to oxidative stress in old rats. PMID- 2574565 TI - [Interstitial pneumonitis following high-dose MCNU]. AB - We describe a 11-year-old boy with NHL, who developed interstitial pneumonitis following high-dose MCNU with autologous peripheral stem cell transfusion. Non productive cough, malaise and progressive dyspnea on exertion were noticed 7 weeks after high-dose MCNU (600 mg/kg) treatment, and chest X-ray revealed a bibasilar reticular pattern. Arterial blood was hypoxemic and pulmonary function showed the development of a restrictive ventilatory effect and a reduced diffusing capacity for carbon monoxide (DLCO). Clinical Symptoms were resolved after 3 courses of m-PSL pulse therapy and 6 months prednisolone, but an isolated reduction in DLCO has been present. This case suggests that pulmonary toxicity is a dose limiting factor for MCNU treatment. PMID- 2574566 TI - Reduced susceptibility to syncope during postural tilt in old age. Is beta blockade protective? AB - Clinical studies of syncope suggest a decreased prevalence of vasovagal syncope in old age. To examine this possibility and its pathophysiologic implications, we report the results of two studies. The first evaluated responses to head-up tilt in young and old subjects. Presyncopal vasovagal symptoms occurred in 4 of 9 young subjects and only 1 of 22 old subjects. The second study asked whether decreased beta-adrenergic responsiveness protected the old during tilt via unopposed alpha-adrenergic-mediated vasoconstriction. Blood pressure, heart rate, and forearm vascular resistance responses to tilt in 11 healthy young subjects randomized to receive intravenous propranolol hydrochloride or saline were compared with those of 10 healthy elderly. Propranolol attenuated heart rate and forearm vascular resistance responses. Vasovagal symptoms occurred in 4 young and no old subjects; 2 were symptomatic during propranolol administration. Thus, presyncopal vasovagal symptoms are less common during tilt in old age. Propranolol did not prevent the vasovagal reaction or enhance forearm vasoconstriction. Propranolol's attenuation of vasoconstriction may be due to decreased activation of cardiopulmonary baroreceptors during beta-blockade. PMID- 2574567 TI - Screening for the multiple endocrine neoplasia syndrome type I. A study of 11 kindreds in The Netherlands. AB - Since 1974, a total of 11 families with the multiple endocrine neoplasia syndrome type I (MEN-I), including 52 patients, were identified. Fifteen of these 52 patients died of MEN-I-related complications (mean age, 44 years), most of them in the period before screening was started. In 11 of the 15 patients, death was caused by complicated peptic ulcer disease, in 2 by metastasis of an endocrine pancreatic tumor, and in 2 by renal failure due to hyperparathyroidism. Family screening led to the diagnosis of 43 new endocrine lesions: 21 cases of hyperparathyroidism, 16 endocrine pancreatic tumors, and 6 pituitary tumors. Hyperparathyroidism either was the first manifestation of MEN-I or was diagnosed simultaneously with the other components of the syndrome in 44 (94%) of the 47 patients who underwent full evaluation. PMID- 2574568 TI - Platelet aggregation induced by alpha 2-adrenoceptor and protein kinase C activation. A novel synergism. AB - Adrenaline or UK 14304 (a specific alpha 2-adrenoceptor agonist) and phorbol ester (phorbol 12,13-dibutyrate; PdBu) or bioactive diacylglycerols (sn-1,2 dioctanoylglycerol; DiC8) synergistically induced platelet aggregation and ATP secretion. The effect on aggregation was more pronounced than the effect on secretion, and it was observed in aspirinized, platelet-rich plasma or suspensions of washed aspirinized platelets containing ADP scavengers. No prior shape change was found. In the presence of adrenaline, DiC8 induced reversible aggregation and PdBu evoked irreversible aggregation that correlated with the different kinetics of DiC8- and PdBu-induced protein kinase C activation. Adrenaline and UK 14304 did not induce or enhance phosphorylation induced by DiC8 or PdBu of myosin light chain (20 kDa), the substrate of protein kinase C (47 kDa), or a 38 kDa protein. Immunoprecipitation studies using a Gcommon alpha antiserum or a Gi alpha antiserum showed that Gi alpha is not phosphorylated after exposure of platelets to PdBu or PdBu plus adrenaline. Adrenaline, PdBu or adrenaline plus PdBu did not cause stimulation of phospholipase C as reflected in production of [32P]phosphatidic acid. Adrenaline caused a small increase of Ca2+ in the platelet cytosol of platelets loaded with Indo-1; this effect was also observed in the absence of extracellular Ca2+. However, under conditions of maximal aggregation induced by adrenaline plus PdBu, no increase of cytosolic Ca2+ was observed. Platelet aggregation induced by PdBu plus adrenaline was not inhibited by a high intracellular concentration of the calcium chelator Quin-2. These experiments indicate that alpha 2-adrenoceptor agonists, known to interact with Gi, and protein kinase C activators synergistically induced platelet aggregation through a novel mechanism. The synergism occurs distally to Gi protein activation and protein kinase C-dependent protein phosphorylation and does not involve phospholipase C activation or Ca2+ mobilization. PMID- 2574569 TI - Inhibition of biliary cholesterol and phospholipid secretion during cyclobutyrol induced hydrocholeresis. AB - The effects of sodium cyclobutyrate, a synthetic hydrocholeretic drug, on biliary lipid secretion and on the biliary outputs of several plasma-membrane enzymes were investigated in anaesthetized rats. Administration of a single oral dose of cyclobutyrol (0.72 mmol/kg body wt.) reduced biliary concentration and output of cholesterol and phospholipid. However, bile acid secretion was not significantly modified. This uncoupling effect of lipid secretion remained even when the choleretic response to the drug had ceased. It additionally led to a statistically significant decrease in the cholesterol/bile acid and phospholipid/bile acid molar ratios and in the lithogenic index of the bile. The biliary outputs of the plasma-membrane enzymes alkaline phosphatase and gamma glutamyltransferase were markedly reduced by the drug. When cyclobutyrol was administered to rats which had been previously fed with a high-cholesterol diet, the effects of cyclobutyrol persisted, but were less marked. Our results demonstrate that the bile acid-independent choleresis induced by cyclobutyrol (related to its pharmacokinetic effect) is accompanied by a pharmacodynamic action that selectively reduces the secretion of biliary lipids. This is due to an uncoupling of the secretion of cholesterol and phospholipids from that of bile acids. Possible explanations for the biliary response to cyclobutyrol are discussed. PMID- 2574570 TI - Formation of N epsilon-(gamma-glutamyl)-lysine isodipeptide in Chinese-hamster ovary cells. AB - N epsilon-(gamma-Glutamyl)-lysine isodipeptide was detected in a protein-free fraction of Chinese-hamster ovary cells and their culture fluid by using radioactive lysine as a tracer. The identity of the isodipeptide was established by its separation on ion-exchange chromatography, analysis by h.p.l.c. after derivatization, recovery of lysine after acidic hydrolysis or after cleavage by a specific enzyme, namely gamma-glutamylamine cyclotransferase. The amount of isodipeptide was raised (460 pmol/10(7) cells and 61 pmol/ml of culture fluid were observed as highest values) as the cell density increased. Effects of inhibitors of intracellular protein degradation have shown that the isodipeptide derives from cross-linking N epsilon-(gamma-glutamyl)-lysine bonds formed by tissue transglutaminase. Estimated half-life values of cross-linked proteins were about 3 h. gamma-Glutamylamine cyclotransferase, which may split the isodipeptide formed during the continuous turnover of cross-linked proteins, was also found in Chinese-hamster ovary cells. Isodipeptide may have been accumulated when either its generated amount is beyond the capacity of gamma-glutamylamine cyclotransferase or it is generated in cell compartments where this enzyme is not present. PMID- 2574571 TI - Potent and selective inactivation of cysteine proteinases with N-peptidyl-O-acyl hydroxylamines. AB - A series of N-peptidyl-O-acyl hydroxylamines was synthesized and tested as inactivators of cysteine proteinases. Depending on the structure of the peptidyl residue of the inhibitors, rapid and complete irreversible inactivation of the lysosomal cathepsins, B, L and S, may be achieved. The most effective inhibitors display second-order rate constants of the inactivation in the range 10(5)-10(6) M-1.s-1. By contrast, the activity of the aminoendopeptidase cathepsin H is only negligibly affected by the N-terminal-protected peptidyl inhibitors. PMID- 2574572 TI - Sex-related differences in the enhancing effects of perfluoro-octanoic acid on stearoyl-CoA desaturase and its influence on the acyl composition of phospholipid in rat liver. Comparison with clofibric acid and tiadenol. AB - The effects of the peroxisome proliferators clofibric acid (p chlorophenoxyisobutyric acid), tiadenol [2,2'-(decamethylenedithio)diethanol] and perfluoro-octanoic acid (PFOA) on hepatic stearoyl-CoA desaturation in male and female rats were compared. Treatment of male rats with the three peroxisome proliferators increased markedly the activity of stearoyl-CoA desaturase. Administration of clofibric acid or tiadenol to female rats increased greatly the hepatic activity of stearoyl-CoA desaturase, the extent of the increases being slightly less pronounced than those of male rats. In contrast with the other two peroxisome proliferators, however, PFOA did not change the activity of stearoyl CoA desaturase in female rats. Hormonal manipulations revealed that this sex related difference in the effect of PFOA on stearoyl-CoA desaturase activity is strongly dependent on testosterone. The increase in stearoyl-CoA desaturase activity by peroxisome proliferators was not accompanied by any notable increases in the microsomal content of cytochrome b5 or the activity of NADH: cytochrome b5 reductase. The administration of the peroxisome proliferators greatly altered the acyl composition of hepatic phosphatidylcholine and phosphatidylethanolamine (namely the proportions of C18:1 and C20:3,n-9 fatty acids increased in both phospholipids), and the alterations were partially associated with the increase in stearoyl-CoA desaturase activity. PMID- 2574573 TI - Identification of Gly-Pro-Glu (GPE), the aminoterminal tripeptide of insulin-like growth factor 1 which is truncated in brain, as a novel neuroactive peptide. AB - A truncated form of IGF-1 which lacks the aminoterminal tripeptide Gly-Pro-Glu (GPE) is found in human brain. It was proposed that GPE may result from neural specific processing and also have a function within the CNS. GPE was synthesized and shown to inhibit glutamate binding to the N-methyl-D-aspartate (NMDA) receptor. Whilst the carboxyterminal glutamate was necessary for NMDA receptor binding, the aminoterminal glycine potentiated receptor crossreaction. Furthermore, GPE had a potent stimulatory effect on the potassium induced release of acetylcholine from rat cortical slices. A less potent stimulation of dopamine release from striatum was also observed. The specific competitive NMDA receptor antagonist, (+/-)2-amino-7-phosphonoheptanoate (AP7), inhibited the action of GPE on dopamine but not on acetylcholine release. These studies have identified GPE as a novel neuroactive peptide with a potent action on acetylcholine release and support the general concept that the proteolytic products of the IGF-1 precursor play a role in the regulation of brain function. PMID- 2574575 TI - Selective membrane toxicity of aminoglycoside antibiotics in membrane vesicles isolated from proximal renal tubules of the rat. AB - A considerable body of evidence suggests that the nephrotoxic potential of aminoglycoside antibiotics may be associated with the degree of membrane binding and subsequent membrane damage in the renal tubules. In this study, we isolated functional basolateral and luminal membrane vesicles from rat renal cortex, incubated each membrane type in the presence of 1 mM concentrations of either neomycin, netilmicin, gentamicin, hydroxygentamicin, or amikacin, and monitored the activities of the marker enzymes alkaline phosphatase (ALP) and lambda glutamyltransferase (GGT) (luminal) or ouabain-sensitive Na+,K+-ATPase (basolateral) to determine if there were any selective drug-related alterations of enzyme activities. While none of the five aminoglycosides had any substantive effect upon enzyme activities of luminal vesicles, all five drugs inhibited the basolateral marker enzyme. Neomycin produced the greatest inhibition, hydroxygentamicin and amikacin the least, and gentamicin and netilmicin were intermediate in the inhibition of the enzyme. These results are in accordance with the known relative nephrotoxicity of these same drugs and indicate the usefulness of isolated renal membrane vesicles for in vitro toxicological studies of novel aminoglycosides. PMID- 2574574 TI - A study of the mechanism of resistance to Adriamycin in vivo. Glutathione metabolism, P-glycoprotein expression, and drug transport. AB - A spontaneously originated murine mammary adenocarcinoma (16C), selected for its sensitivity to agents active against breast cancer in women, and one of the very few experimental solid tumor models responsive to Adriamycin (ADR) was used to study the mechanism of induced ADR resistance in vivo. A resistant variant of the tumor was obtained from the explant of a regrown tumor following a dose of ADR (12 mg/kg) that caused complete tumor repression but not cure. Progressive refractoriness to ADR was observed following up to six repeated cycles of treatment, regression and regrowth. However, beyond the sixth treatment, no further degree of resistance could be obtained. The cell line so established, designated 16C/ADRR, has a glutathione (GSH) content 1.67 times greater than the parent 16C line. Depletion of GSH by buthionine sulfoximine (BSO) enhanced the cytoxicity of ADR in both cell lines. The sensitization effect appeared to be dependent on the degree of GSH depletion, requiring a threshold level of depletion to approximately 30% of control. The resistance of 16C/ADRR, however, appeared not to be directly related to the increased absolute GSH level per se since reduction of the GSH content of the 16C/ADRR line to levels similar to that of the parent 16C line did not restore the original sensitivity to ADR. However, the activities of two important elements in the GSH detoxification system, GSH peroxidase and S-transferase, were found to be elevated in resistant cells by factors of 2.4 and 4.7-5.6 respectively. In vivo studies with a diverse spectrum of antineoplastic drugs revealed a pattern of cross-resistance consistent with the idea that elevated GSH S-transferase and peroxidase activities may be responsible for the decreased (2.8- to 5.3-fold) sensitivity to ADR. 16C/ADRR exhibited cross-resistance with melphalan (MEL), but none with vincristine (VCR), vinblastine (VBL) or etoposide (VP-16). These results clearly demonstrate non adherence by the 16C/ADRR tumors to the well characterized multidrug resistance (mdr) phenotype. Further affirmation of this conclusion was obtained by immunochemical and pharmacological studies. When a monoclonal antibody prepared against the mdr associated, 170 kD P-glycoprotein (170 P-gp), was used, the presence of the 170 kD P-gp in both the sensitive and resistant 16C lines could not be detected, although the presence of a lower molecular weight form of P-gp could not be ruled out entirely. High performance liquid chromatographic measurement of ADR accumulation and elimination also failed to reveal any significant differences between the sensitive and resistant variants.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2574576 TI - Stimulation of glutamine metabolism by the antiepileptic drug, sodium valproate, in isolated dog kidney tubules. AB - The effects of sodium valproate, a widely used antiepileptic drug and an hyperammonemic agent, on glutamine and glutamate metabolism were studied in isolated dog kidney tubules. Valproate markedly stimulated glutamine removal as well as the formation of ammonia, aspartate, pyruvate, lactate, alanine and glucose; the increase in ammonia formation was explained by a stimulation by valproate of flux not only through glutaminase (EC 3.5.1.2) but also through glutamate dehydrogenase (EC 1.4.1.3). By contrast, valproate did not stimulate glutamate removal or ammonia, aspartate and glucose formation from glutamate; this suggests that the increase in flux through glutamate dehydrogenase with glutamine as substrate was secondary to the increase in flux through glutaminase. Accumulation of pyruvate, alanine and lactate in the presence of valproate was much less from glutamate than from glutamine. Inhibition by amino-oxyacetate of accumulation of aspartate and alanine from glutamine caused by valproate did not prevent the acceleration of glutamine utilization and the subsequent stimulation of ammonia formation. These data are consistent with a stimulatory effect of valproate primarily exerted at the level of glutaminase in dog kidney tubules. However, the fact that assayed activity of glutaminase remained unchanged in the presence of valproate suggests that this compound accelerates flux through the latter enzyme by an indirect mechanism probably related to the renal metabolism of this compound. PMID- 2574578 TI - Lack of association between scleroderma and types I and III procollagen gene restriction fragment length polymorphisms. AB - Restriction fragment length polymorphisms (RFLPs) in types I and III procollagen genes were studied in 62 scleroderma patients and 138 healthy controls. Allelic frequencies were determined for each RFLP, and comparisons were made between the 2 populations, stratifying them by race when appropriate. No statistically significant differences were observed for the frequencies of any of the RFLPs studied. PMID- 2574577 TI - Alkylthio acetic acids (3-thia fatty acids)--a new group of non-beta-oxidizable peroxisome-inducing fatty acid analogues--II. Dose-response studies on hepatic peroxisomal- and mitochondrial changes and long-chain fatty acid metabolizing enzymes in rats. AB - The activity of key enzymes involved in oxidation and esterification of long chain fatty acids was investigated after male Wistar rats were treated with different doses of sulfur substituted fatty acid analogues, 1,10 bis(carboxymethylthiodecane) (BCMTD, non-beta-oxidizable and non-omega oxidizable), 1-mono(carboxymethylthiotetradecane) (CMTTD, trivial name, alkylthio acetic acid, non-beta-oxidizable) and 1-mono(carboxyethylthiotetradecane) (CETTD trivial name, alkylthio propionic acid, beta-oxidizable). The sulfur substituted dicarboxylic acid and the alkylthio acetic acid induced in a dose-dependent manner the mitochondrial, microsomal and especially the peroxisomal palmitoyl-CoA synthetase activity, the mitochondrial and cytosolic palmitoyl-CoA hydrolase activity, the mitochondrial and especially the microsomal glycerophosphate acyltransferase activity and the peroxisomal beta-oxidation, especially revealed in the microsomal fraction. Morphometric analysis of randomly selected hepatocytes revealed that BCMTD and CMTTD treatment increased the number, size and volume fraction of peroxisomes and mitochondria. Thus, the observed changes in the specific activity of fatty acid metabolizing enzymes with multiple subcellular localization can partly be explained as an effect of changes in the s values of the organelles as proliferation of mitochondria and peroxisomes occurred. The most striking effect of the alkylthio propionic acid was the formation of numerous fat droplets in the liver cells and enhancement of the hepatic triglyceride level. This was in contrast to BCMTD treatment which decreased the hepatic triglyceride content. In conclusion, the results provide evidence that administration of non-beta-oxidizable fatty acid analogues had much higher in vivo potency in inducing hepatomegaly and key enzymes involved in fatty acid metabolism, including proliferation of peroxisomes and mitochondria than is exhibited in the beta-oxidizable, alkylthio propionic acid. Moreover, the dicarboxylic acid was apparently three to six times more potent than the alkylthio acetic acid in inducing peroxisomal beta-oxidation and peroxisome proliferation when considered on a mumol/day basis. As palmitic acid and hexadecanedioic acid only marginally affected these hepatic responses, it is conceivable that the potency of the selected compounds as proliferators of peroxisomes and inducers of the associated enzymes depends on their accessibility for beta-oxidation. PMID- 2574579 TI - Spontaneous dissection of the internal carotid artery in a patient with polyarteritis nodosa. PMID- 2574580 TI - Hippocampal nicotinic cholinergic mechanisms mediate spontaneous alternation and fear during ontogenesis but not later in the rat. AB - Spontaneous alternation was examined in young rats following microinjections of antinicotinic agents into one of the 4 hippocampal sites: anterodorsal, or posteroventral dentate gyrus, hippocampal gyrus, or entorhinal cortex. In control and saline-injected animals, the alternation rate was shown to grow suddenly from 40 to 80% between days 15 and 17 (the adult level being 85-90%), to regress partly (to 55%) between days 20 and 30, and return to a near-adult level (75%) by day 40. Meanwhile fear responses to environment (defecation and vocalization) emerged between days 20 and 25, increased to a maximum until day 30, and returned to the typically low adult level by day 40. Injections of mecamylamine (5, 20 micrograms) or hexamethonium (5, 20 micrograms) into any of the 4 sites significantly reduced the rate of alternation from as early as day 10 on, but were no longer effective from day 30 on; on the other hand, they did not alter the level of defecation, but had a tendency to lower the level of vocalization on day 30 only. These results indicate that hippocampal nicotinic cholinergic mechanisms play a role in spontaneous alternation and appear to be involved in the control of one fear reaction (vocalization) until day 30. PMID- 2574581 TI - Correlation between carbohydrate structures on the envelope glycoprotein gp120 of HIV-1 and HIV-2 and syncytium inhibition with lectins. AB - The binding of 13 different lectins to gp120 partially purified from two HIV-1 isolates and one HIV-2 isolate was studied by in situ staining on electrophoretically separated and electroblotted HIV antigens. The lectins concanavalin A, wheat germ agglutinin, Lens culinaris agglutinin, Vicia faba agglutinin, Pisum sativum agglutinin and phytohaem(erythro)agglutinin bound to gp120 of all three isolates. The carbohydrate of gp120 recognized by lectins was thus arranged in at least four types of glycans: a high mannose type glycan, a bisected hybrid or complex type glycan, a biantennary fucosylated complex type glycan and a triantennary bisected complex type glycan. Only lectins which bound at least one of the four types of glycans were capable of inhibiting fusion of HIV-infected cells with CD4 cells by a carbohydrate-specific interaction with the HIV-infected cells. Thus, several different glycan structures may be implicated in CD4-gp120 binding. PMID- 2574582 TI - Inhibitory effect of glycosides like saponin from soybean on the infectivity of HIV in vitro. AB - Soybean saponins isolated from soybean seeds were investigated for their antiviral activity on HIV in vitro, using an HTLV-I-carrying cell line, MT-4. Saponin B1 completely inhibited HIV-induced cytopathic effects and virus-specific antigen expression 6 days after infection at concentrations greater than 0.5 mg/ml. Saponin B2 also inhibited HIV infection, although less potently. Both saponin B1 and B2 had no direct effect on the reverse transcriptase activity of HIV. Saponin B1 also inhibited HIV-induced cell fusion in the MOLT-4 cell system. The results of this study suggest that soybean saponins, especially saponin B1, have inhibitory activity against HIV infection. PMID- 2574583 TI - Stimulation of peripheral blood lymphocytes of HIV-infected patients by jacalin, a lectin mitogenic for human CD4+ lymphocytes. AB - The proliferative response of peripheral blood mononuclear cells stimulated by jacalin was investigated in 157 samples from 104 HIV-infected patients at various clinical stages of disease. Jacalin proliferative response correlated with the absolute numbers and percentages of CD4+ lymphocytes and with the percentages of Leu 8 lymphocytes. It correlated negatively with the percentages of CD8+ and CD38+ lymphocytes. It was depressed during acute HIV infection and at advanced stages. The response in Centers for Disease Control groups II and III was heterogeneous and similar; in both, some patients showed a very low response. Further follow-up of the present patients should indicate whether jacalin responsiveness has a prognostic value. PMID- 2574584 TI - Amplified replication of Toxoplasma gondii parasites in a human T-cell line persistently infected with HIV-1. PMID- 2574585 TI - Lymphocytes' intrinsic lymphoproliferative capacity in patients with AIDS treated with zidovudine. PMID- 2574586 TI - Structural study of histamine H2-receptor antagonists. Five 3-[2-(diamino methyleneamino)-4-thiazolylmethylthio]propionamidine and -amide derivatives. AB - (1) N2-Cyano-3-[2-(diaminomethyleneamino)-4- thiazolylmethylthio]propionamidine monohydrate, C9H13N7S2.H2O, Mr = 301.39, P1, a = 11.089 (4), b = 9.130 (6), c = 7.033 (5) A, alpha = 100.99 (6), beta = 83.86 (5), gamma = 86.80 (7) degrees, V = 692.9 (6) A3, Z = 2, Dm = 1.443 (2), Dx = 1.444 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 34.86 cm-1, F(000) = 316, T = 293 K, R = 0.043 for 2219 reflections. (2) 3-[2-Diaminomethyleneamino)-4- thiazolylmethylthio]-N2 sulfamoylpropionamidine (famotidine) hydrochloride, C8H15N7O2S3.HCl, Mr = 373.90, Cc, a = 15.205 (3), b = 14.442 (3), c = 9.262 (1) A, beta = 124.00 (5) degrees, V = 1686.1 (7) A3, Z = 4, Dm = 1.470 (2), Dx = 1.473 g cm-3, mu(Cu K alpha) = 56.09 cm-1, F(000) = 776, T = 293 K, R = 0.036 for 1411 reflections. (3) 3-[2 (Diaminomethyleneamino)-4-thiazolylmethylthio]-propi ona mide, C8H13N5OS2, Mr = 259.35, P2(1)2(1)2(1), a = 5.472 (1), b = 18.260 (5), c = 11.890 (3) A, V = 1188.0 (5) A3, Z = 4, Dm = 1.448 (1), Dx = 1.450 g cm-3, mu(Cu K alpha) = 39.26 cm-1, F(000) = 544, T = 293 K, R = 0.036 for 1260 reflections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574587 TI - Primary hypertension, neural tone, and behavior. Role in pressor responses to stress. AB - Patients with primary hypertension follow a hierarchical pattern of hemodynamic and neurohumoral responses to laboratory and environmental mental and physical stress. The stressor responses are regulated by the central and peripheral autonomic nervous system. The psychological and behavioral characteristics of these persons--for example, whether they conform to the Type A pattern of behavior, including hostility and anxiety--alter the magnitude and duration of their stress responses. For some patients, the magnitude of the neurohumoral activation can predict the effectiveness of therapy with sympatholytic and other types of drugs used to treat hypertension. PMID- 2574588 TI - The C1 area of the rostral ventrolateral medulla oblongata. A critical brainstem region for control of resting and reflex integration of arterial pressure. AB - A population of neurons localized to a small region of the brain stem reticular formation, the rostral ventrolateral reticular nucleus (RVL), is the principal area of the brainstem regulating resting, reflex, and probably behaviorally coupled control of arterial pressure. The critical area of the RVL reticular nucleus engaged in cardiovascular control surrounds a cluster of adrenergic neurons of the C1 group, and is therefore designated the C1 area. C1 area neurons have a direct and extremely potent synaptic relationship with preganglionic sympathetic neurons of the intermediolateral (IML) nucleus of the spinal cord. Neurons in the C1 area are tonically active and fire in relationship to the cardiac cycle, a rhythm imposed by baroreceptors. They thereby provide the background of excitation to preganglionic neurons to maintain normal resting arterial pressure. Which transmitter released by C1 area neurons produces sympathetic excitation is uncertain, but it may be glutamate. C1 area neurons are critical to the integration of a wide range of cardiovascular reflexes, including the arterial pressure responses to arterial baroreceptor, chemoreceptor, and other cardiopulmonary receptor stimulation, to pain and possibly to exercise, to brain stem ischemia and distortion, and probably to the arterial pressure elevations associated with emotional behavior. The cardiovascular neurons of the C1 area are responsive to the actions of a number of neurotransmitters, many of which are confined to local circuit neurons in the region, including gamma aminobutyric acid (GABA), catecholamines, acetylcholine, and several opiates. They also appear to be the site of action upon arterial pressure of a number of drugs--including clonidine and possibly the beta-blockers. Neurons of the C1 area of the RVL reticular nucleus, therefore, appear to function as one of the most critical output systems of the brain for regulating arterial pressure in health and sickness. PMID- 2574589 TI - [Properties of the postsynaptic depolarization produced by glutamate on the vestibular receptors in frogs]. AB - In order to investigate the possible role of glutamate (Glu) as afferent transmitter in the vestibular system, this agent was tested on sensory organs of frog semicircular canals. Intracellular recordings from single afferent axons in isolated labyrinths showed that, after blocking chemical transmission with high Mg++ (12 mM), micro-injections of Glu (5 mM-15 ul) elicited a long lasting postsynaptic depolarization. The amplitude of this depolarization was reduced dose dependently after addition of the amino acid antagonists Kynurenic acid or gamma-D-glutamylglycine to the bath. When the Na+ concentration in the bath was progressively reduced, the depolarization decreased gradually and disappeared almost completely in Na(+)-free Ringer. The removal of K+ affected the depolarization to a lesser extent: in K(+)-free Ringer depolarization decreased only by 30-40%. On the contrary, the complete substitution of Ca++ ions in the bath was without effect. Our results suggest that in the frog semicircular canals the postsynaptic depolarization induced by Glu involves the activation of non NMDA type of amino acid receptors, probably coupled to channels selective for Na+ and K+ ions. The present findings are consistent with the hypothesis that Glu or a related substance may be the transmitter released at the afferent synapses of the vestibular receptors. PMID- 2574590 TI - Activities of dipeptidyl peptidases in BXSB mice and MRL/lpr mice with lupus erythematosus-like syndrome. AB - Activities of peptidases were examined in tissues of male BXSB and male MRL/Mp lpr/lpr (MRL/lpr) mice which are animal models of human systemic lupus erythematosus. Female BXSB and male MRL/+ + mice without histopathological changes were used as controls. Activity of DPP II in the spleen, kidney, and liver showed an increase at 13 and 20 weeks of age, while that of DPP IV was decreased at 20 weeks of age, as compared to control mice. The ratio of DPP II/DPP IV activities in the tissues was significantly increased and these findings agree with our previous results in the tissues of NZB mice and in the serum of patients with lupus erythematosus, underscoring the importance of hydrolytic enzymes in the pathogenesis of autoimmune diseases. PMID- 2574591 TI - Molecular genetics of development studied in the transgenic mouse. PMID- 2574592 TI - Simple and complex cell cycles. PMID- 2574593 TI - Venovenous extracorporeal life support in neonates using a double lumen catheter. AB - After satisfactory development and testing of a polyurethane 14 Fr double lumen catheter, we used this device for venovenous extracorporeal life support in neonates who had respiratory failure. This catheter was designed for single site cannulation of the internal jugular vein, thereby sparing the carotid artery from ligation. Cannulation was successful in 17 of 21 neonates, with 15 successful venovenous runs, whereas 2 of the 17 patients were converted to venoarterial bypass because of inadequate support. Oxygenation and CO2 removal were adequate in the remaining patients. Average time on bypass was 111 hours. All 15 patients survived, and exploration of the cannulation site for bleeding was required in three patients. Preoxygenator pressure, recirculation of oxygenated blood, and hemolysis were all within acceptable levels during each run. Venovenous extracorporeal life support with the double lumen catheter can replace venoarterial access in most cases of neonatal respiratory failure. PMID- 2574594 TI - Failure of terfenadine in relieving the pruritus of atopic dermatitis. AB - We report the results of a double-blind, placebo-controlled, cross-over study of terfenadine 120 mg twice daily for pruritus in atopic dermatitis. Twenty-eight subjects with chronic atopic dermatitis received both terfenadine 120 mg b.d. and placebo each for a period of 1 week. Response was recorded by the subjects using visual analogue scales for severity of pruritus twice daily for the last 4 days of each treatment phase. There was no benefit from terfenadine. PMID- 2574595 TI - Levels of mRNAs coding for lipogenic enzymes in rat lung upon fasting and refeeding and during perinatal development. AB - The relative amounts of mRNAs coding for fatty-acid synthase (EC 2.3.1.85), acetyl-CoA carboxylase (EC 6.4.1.2), ATP citrate lyase (EC 4.1.3.8) and malic enzyme (EC 1.1.1.40) were determined in lungs and livers of adult rats that were normally fed, starved for 48 h or starved for 48 h and subsequently refed for 72 h with a carbohydrate-rich, fat-free diet. In the liver, starvation caused a small decrease in the relative abundance of the mRNAs which was not statistically significant. Subsequent refeeding caused a statistically significant increase in mRNAs for all of the enzymes studied. In the lung, no significant changes were found, indicating that the regulation of the abundance of mRNAs encoding the lipogenic enzymes in the lung differs from that in the liver. In the developing rat lung, mRNA for fatty-acid synthase increased 3-fold in abundance between fetal days 18 and 20 and decreased directly after birth (at day 22 of gestation). A similar pattern was observed for ATP citrate lyase mRNA. The level of acetyl CoA carboxylase mRNA decreased significantly after birth. These observations indicate that in perinatal rat lungs, pretranslational regulation is involved in the control of the synthesis of these enzymes. The abundance of acetyl-CoA carboxylase mRNA did not change in the prenatal period, a time during which the specific activity of this enzyme increases. This lack of correlation between the specific activity of acetyl-CoA carboxylase and the abundance of its mRNA may indicate that translational regulation of the synthesis of the enzyme or post synthetic regulatory effects on enzyme molecules are involved in the control of this enzyme in the prenatal period. No changes in the abundance of lung malic enzyme mRNAs were observed throughout the perinatal period. PMID- 2574596 TI - Altered acyl-CoA metabolism in riboflavin deficiency. AB - We have recently described the effects of riboflavin deficiency on the metabolism of dicarboxylic acids (Draye et al. (1988) Eur. J. Biochem. 178, 183-189). As both mitochondria and peroxisomes are thought to be involved, we have examined the activities of various enzymes in these organelles in the livers of riboflavin deficient rats. Mitochondrial beta-oxidation of fatty acids was severely depressed due to loss of activity of the three fatty acyl-CoA dehydrogenases, whereas there was an enhancement of peroxisomal beta-oxidation due to an increased activity of the FAD-dependent fatty acyl-CoA oxidase, although the activities of other peroxisomal flavoproteins, D-amino acid oxidase and glycolate oxidase, were lowered. Hepatocyte morphometry revealed an increase in the numbers of peroxisomes, indicating a proliferation induced by the deficiency. The mitochondrial acyl-CoA dehydrogenases involved in branched-chain amino acid metabolism were also severely decreased leading to characteristic organic acidurias. There was some loss of activity of the flavin-dependent sections of the electron transport chain (complexes I and II), but these were probably not sufficient to affect normal function in vivo. The specificity of these effects allows the use of the riboflavin-deficient rat as a model for the study of dicarboxylate metabolism. PMID- 2574597 TI - Proton NMR and CD solution conformation determination and opioid receptor binding studies of a dynorphin A(1-17) model peptide. AB - The opioid peptide dynorphin A(1-17) contains a peptide segment in residues 7-15 with the potential to form an amphiphilic beta-strand. This amphiphilic structure may, like the amphiphilic alpha-helices found in many other peptide hormones, be an important determinant of its interactions with membranes and receptors. In order to investigate and characterize these interactions, we have synthesized a 17-residue dynorphin analogue (YGGFLKKVKPKVKVKSS) that incorporates a peptide model of this amphiphilic secondary structure with minimized homology (25%) relative to the native sequence. This peptide exhibits the full biological potency of dynorphin in assays of kappa-opioid receptor binding, and is more selective for this type of opioid receptor than the natural peptide. The conformation of the model peptide in aqueous solution has been investigated in detail by NMR spectroscopy. The values of the NH-CH alpha coupling constants together with rotating frame NOEs indicate the presence of an amphiphilic structure together with some beta-strand structure in residues 7-15, and demonstrate that a peptide model that stabilizes this structure in aqueous solution and enhances kappa-opioid receptor selectivity can be successfully designed using using alternating lysine and valine residues. PMID- 2574598 TI - Regulation of particulate guanylate cyclase by atriopeptins: relation between peptide structure, receptor binding, and enzyme kinetics. AB - Structural analogs of atriopeptins (APs) were compared for their ability to activate particulate guanylate cyclase and bind to specific receptors in rat adrenal membranes. All analogs tested increase Vmax without altering the concentration of substrate required for half-maximum activity or the positive coperativity exhibited by the enzyme. Maximum velocities (pmoles of cGMP produced per min per mg protein) achieved in the absence and presence of APs were 128.3 +/ 6.6 and 283.8 +/- 20.6 using Mn2+-GTP, and 53.7 +/- 3.7 and 149.9 +/- 7.6 using Mg2+-GTP as the substrate, respectively. Although all APs were equally efficacious in activating the enzyme, their rank potency was ANF (8-33) = AP III = AP II greater than AP I when either divalent cation was used as the cofactor. The EC50 for activation of guanylate cyclase by AP I was about 10(-7) M, while that for the other peptides was about 10(-8) M, using either divalent cation cofactor. 125I-labeled ANF bound to rat adrenal membranes with a KD of 5.10(-10) M. Although all APs were equally efficacious in competing with labeled ANF for receptor binding, their rank potency was identical to that for enzyme activation. The Ki for AP I was about 10(-8) M, while that for the other peptides was about 10(-10) M. These data suggest that the carboxy terminal Phe-Arg present in the AP analogs except AP I and critical for biological and receptor-binding activity are also important in coupling receptor-ligand interaction with guanylate cyclase activation. The correlation between the rank order potency for receptor binding, enzyme activation, and the reported physiological actions of APs support the suggestion of a functional coupling between these proteins. PMID- 2574599 TI - Regulation of transcription of the glnALG operon of Escherichia coli by protein phosphorylation. AB - The transcription of glnA, the structural gene for glutamine synthetase in enteric bacteria, is regulated by the phosphorylation and dephosphorylation of an effector protein, NRI. In its phosphorylated form the effector activates the initiation of transcription at promoters specific of sigma 54, rather than the abundant sigma 70. The ability of NRI-phosphate to stimulate the formation of open promoter-sigma 54 RNA polymerase complexes is enhanced by specific binding sites, located in the case of glnA 100 and 130 base pairs upstream from the transcriptional start site. These sites can be moved more than 1000 base pairs upstream or downstream without losing their effectiveness. The phosphorylation and dephosphorylation of NRI-NRI-phosphate is catalyzed by the modulator protein NRII. Its activity is controlled by an intracellular signal, the ratio of glutamine to 2-ketoglutarate, which is generated by glutamine synthetase in response to the environmental stimulus, the availability or lack of ammonia. The signal is transduced to the modulator by means of 2 additional proteins: uridylytransferase and PII. PMID- 2574600 TI - [Role of the endothelium in the development of reactive hyperemia]. AB - The experiments on anesthetized dogs demonstrated that reaction of the femoral vessels reactive hyperemia essentially decreased after chemical inhibition of endothelium by saponin, inhibition of lipoxygenase by quercetin and guanylate cyclase by methylene blue. Reaction was increased after cyclooxygenase inhibition by indomethacin. We concluded that the endothelium plays an important role in reaction of reactive hyperemia by endothelium-derived relaxing factor release. PMID- 2574601 TI - [Activity of lysosomal enzymes in drug-induced lesions of the liver]. AB - In the experiments on Wistar rats we showed that administration of ulcerogenic drugs (cinchophen, acetylsalicylic acid, butadione, indomethacin etc.) produced the alterations of free activity of lysosomal enzymes in the homogenates of ulcerated stomach, presumably the significant elevation of the activity of cathepsins (more often cathepsin with optimum of activity at pH 5.5) and the significant reduction of free activity of acid nucleases (more often of DNA-ase). The alterations of free activity of lysosomal enzymes were as in cases with gastric ulcerations as in cases with unaffected stomach. PMID- 2574602 TI - Molecular biology of factor X. PMID- 2574603 TI - Inpatient heroin detoxification: a comment. PMID- 2574604 TI - Mumps, measles, and rubella vaccination and encephalitis. PMID- 2574605 TI - The impact of molecular genetics on our understanding of the psychoses. AB - Studies demonstrating the linkage to separate chromosomal locations of Alzheimer's disease, manic depression, and schizophrenia require re-evaluation of our ideas of their genetic aetiology. This article reviews the findings, and explores the increasing contribution of the 'new genetics' to our understanding of the organic and functional psychoses. PMID- 2574606 TI - A comparison of in-patient and out-patient prescribing. AB - The prescribing of psychotropic medication to 96 attenders at a lithium clinic was compared with their prescriptions while in-patients. As out-patients, they received fewer psychotropic drugs fewer times a day. This suggests that psychiatrists do not adopt intransigent stances in favour of polypharmacy and irrational psychotropic prescribing, as previous studies have implied. Caution is advised before attributing apparently irrational prescribing to bad clinical practice, or advocating remedial action aimed at changing the habits of prescribers. PMID- 2574607 TI - A rating scale for drug-induced akathisia. AB - A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisia, and mild, moderate, and severe akathisia. It comprises items for rating the observable, restless movements which characterise the condition, the subjective awareness of restlessness, and any distress associated with the akathisia. In addition, there is an item for rating global severity. A standard examination procedure is recommended. The inter-rater reliability for the scale items (Cohen's kappa) ranged from 0.738 to 0.955. Akathisia was found in eight of 42 schizophrenic in-patients, and nine had pseudoakathisia, where the typical sense of inner restlessness was not reported. PMID- 2574608 TI - Thirty years' war: a battle with insomnia. AB - A 72-year-old man with a 30-year complaint of intractable insomnia had a positive family history of depression. He first came to psychiatric attention in 1958, after attacking his wife. He was prescribed barbiturates, and later was given meprobamate and nitrazepam, but with no effect on his complaint. The patient tended to increase the dosage of any drug given, of his own accord. EEG sleep recording confirmed the diagnosis of nocturnal myoclonus. It was hoped that at the case conference further treatment stratagems would be suggested. PMID- 2574609 TI - The damnation of benzodiazepines. AB - It is argued that there are two kinds of benzodiazepine dependence: a therapeutic and a morbid kind. The therapeutic dependence is acceptable in that it mitigates the clinical manifestations in patients with long-standing and fluctuating anxious-depressive symptoms. The morbid dependence is an unfortunate complication which can arouse therapeutic concern because it ties patients to an excessive dosage, unless the penalty of a sometimes grim abstinence syndrome is paid on drug reduction. The present, often strident and threatening, damnation of benzodiazepines oversteps the mark and causes avoidable misery to patients whose well-being has become largely and therapeutically dependent on the drug. PMID- 2574610 TI - Two cases of agranulocytosis on addition of a butyrophenone to a long-standing course of phenothiazine treatment. AB - Two cases of agranulocytosis occurring after addition of a butyrophenone to a course of phenothiazine treatment are reported and possible mechanisms for this interaction are discussed. PMID- 2574611 TI - Prevalence of benzodiazepine abuse and dependence in psychiatric in-patients with different nosology. An assessment of hospital-based drug surveillance data. AB - Frequencies of abuse and dependence assessed continuously within a drug surveillance system were analysed as a contribution to risk-benefit evaluations of benzodiazepines (BZDs). In 4.7% of 15,296 patients admitted to psychiatric hospitals between 1980 and 1985, BZDs had been involved in some kind of abuse or dependence. Primary BZD dependence, defined as physical dependence on BZDs in patients who had not been dependent before, was observed in about 1% of admitted patients. Linking these data with psychiatric diagnoses revealed a high risk of primary BZD dependence for in-patients (11.8%) with anxiety neurosis (ICD-9, 300.0), and a lower risk for neurotic (300.4) and for endogenous depressives (296.1) (risk 3.7% and 2.7% respectively). Older age was also related to primary BZD dependence. For depressive in-patients, the risk was twice as high in females as in males. Anecdotal observations advocate more systematic investigation of the emotional effects of long-term therapy with BZDs. PMID- 2574612 TI - Benzodiazepine addiction in heroin addicts. PMID- 2574613 TI - A case of doll phobia. AB - A case of doll phobia in a 14-year-old boy is presented and discussed. PMID- 2574614 TI - Treatment of extrapyramidal side-effects. PMID- 2574615 TI - The benefits of physiological psychology. AB - This article asserts that physiological psychology offers specific benefits to theoretical psychology and the real world and also contributes in a more diffuse manner to an integrated perspective of the nature of man. Theoretical topics covered are: perception, with particular reference to pattern recognition; parallel distributed processing; subconscious perception. Real-world problems addressed are: the role of stress in illness; personality, learning and proneness to psychological disorder; the mechanisms of depression and anxiety. There is a brief discussion of eating disorders, sex, aggression, neuropsychology and the role of perceptual variety in brain development. It is argued that conversation between the physiological and psychological levels of explanation benefits theorizing at both levels. PMID- 2574616 TI - Subclavian aneurysm: a presentation of Takayasu's arteritis. PMID- 2574617 TI - Barrett's oesophagus. PMID- 2574618 TI - Dynorphin A(1-8) immunoreactive cell bodies, dendrites and terminals are postsynaptic to calcitonin gene-related peptide primary afferent terminals in the monkey dorsal horn. AB - In the present study, Dynorphin A(1-8) (DYN)-immunoreactive cell bodies, dendrites and terminals are observed postsynaptic to calcitonin gene-related peptide (CGRP)-immunoreactive terminals in laminae I and II. With the demonstration of axosomatic, axodendritic as well as axoaxonic interactions, we hypothesize that CGRP-containing primary afferent terminals can effect processing at the level of the cell body (possibly influencing the manufacture of DYN and/or the firing rate of DYN-containing cells) and also modulate the output of DYN terminals in laminae I and II of the monkey dorsal horn. These structural relationships may play an important role in the processing of noxious input at the spinal cord level. PMID- 2574619 TI - Somatostatin inhibits two types of voltage-activated calcium currents in rat growth-hormone secreting cells. AB - Somatostatin is known as the hypothalamic inhibitor of growth-hormone (GH) secretion from the pituitary gland. The present study examines the effects of somatostatin on voltage-gated calcium currents recorded from enriched populations of normal GH-secreting cells (somatotrophs). Two types of voltage-activated calcium currents were recorded from somatotrophs with the whole-cell mode of the patch-clamp technique. Somatostatin exerted a reversible blocking effect on these two types of calcium currents. These findings suggest that somatostatin can regulate intracellular calcium in somatotrophs by a direct control of calcium fluxes across the plasma membrane of these cells, thereby affecting the level of GH secretion. PMID- 2574620 TI - Opioids can enhance and inhibit the electrically evoked release of methionine enkephalin. AB - The stimulated (40 Hz) release of enkephalin from the myenteric plexus can be modulated by multiple types of opiate receptor. The direction of the modulation is not fixed but is bimodal. Both an inhibition and an enhancement of evoked release is observed depending on the concentration of opioid agonist that is used. Each of these effects can be antagonized by naloxone. Following pretreatment of guinea pig myenteric plexus in vitro with forskolin (0.5 microM) or the lipid soluble cAMP analog 8-(4-chlorphenylthio)-cAMP (8-CPT-cAMP; 100 microM) the inhibition of stimulated Met-enkephalin release that is produced by sufentanil (10(-8) M), [D-Pen2-D-Pen5]enkephalin (DPDPE, 10(-8) M) or dynorphin (10(-7) M) is no longer observed. On the contrary, in forskolin- or 8-CPT-cAMP treated myenteric plexus a previously inhibitory concentration of the above opioids now produces an enhancement of the magnitude of the stimulated Met enkephalin release. Excitatory responses (enhanced release) to lower concentrations of sufentanil (1 nM) or DPDPE (5 nM) are not affected by pretreatment with the same concentration of forskolin or 8-CPT-cAMP. These data suggest that the ability of opioids to enhance or inhibit evoked enkephalin release is mediated via different biochemical processes (separate second messenger systems). This could imply that the opioid enhancement of enkephalin release is due to a direct facilitation of release and not to disinhibition. The ability of opioids to enhance the release of at least some neurotransmitters should be taken into account when attempting to explain the physiological sequelae of the acute and chronic effects of narcotics. PMID- 2574621 TI - Anti-Thy-1 immunotoxin, OX7-saporin, destroys cerebellar Purkinje cells after intraventricular injection in rats. AB - Thy-1 is an abundant surface glycoprotein of rat neurons. OX7 is a monoclonal antibody with high affinity for Thy-1. This study sought to determine if intraventricularly administered OX7 could serve as a carrier to deliver cytotoxin to neurons, thus destroying those neurons. Saporin (Sap), a ribosome-inactivating protein was disulfide-coupled to OX7 (OX7-Sap). OX7-Sap, OX7, saporin alone, pooled non-immune mouse IgG, and an irrelevant immunotoxin, RFT-1-Sap, were injected into the lateral ventricles of anesthetized adult rats. Animals were observed for 1-8 days. OX7-Sap-injected animals developed coarse head tremor and gait/truncal ataxia in a dose-dependent manner beginning 24 h or more after injection. All control animals remained healthy. After OX7 or OX7-Sap injection, immunoperoxidase staining for mouse IgG was most intense and specific in the molecular and Purkinje cell layers of the cerebellar cortex. Cresyl violet staining demonstrated destruction of the Purkinje cell layer in the OX7-Sap treated animals but not in controls. These results indicate that intraventricular injections of OX7 can be used to deliver biologically active moieties to the Purkinje cells. This approach may prove useful in analysis of Purkinje cell function and as a model of cerebellar degeneration. PMID- 2574622 TI - Enhanced behavioral stereotypies elicited by intrastriatal injection D1 and D2 dopamine agonists in intact rats. AB - Five components of behavior elicited by dopamine (DA) agonists (locomotor hyperactivity, sniffing, oral activity, grooming and paw nibbling) were evaluated after bilateral infusion of the selective D1 agonist fenoldopam (SKF 82526; 2.5 10 micrograms), the selective D2 agonist quinpirole (LY 171555; 5-40 micrograms) and the muscarinic cholinergic antagonist scopolamine (5-20 micrograms) into the ventral striatum of awake, unrestrained rats. Simultaneous bilateral infusion of various dose combinations of fenoldopam (2.5-10 micrograms) and quinpirole (5-20 micrograms) elicited dramatic increases in stereotyped behaviors relative to the effects produced by corresponding doses of each drug alone. Stereotyped sniffing and paw nibbling (self-directed oral activity) were markedly enhanced, whereas conventional oral behaviors (licking, chewing and/or biting) were either slightly or not at all increased. These potentiated responses were reduced or blocked by concomitant infusion of either the selective D1 antagonist SCH 23390 (1 and 5 micrograms) or the selective D2 antagonist sulpiride (0.15 microgram). Scopolamine (10 micrograms) only slightly increased the effects of quinpirole (5 micrograms) on both sniffing and oral behaviors, whereas it dramatically potentiated the effects of fenoldopam (2.5 micrograms) on oral activity; sniffing was only slightly increased. The effects of both drug combinations were almost completely antagonized by infusion of either SCH 23390 (1 microgram) or sulpiride (0.1 microgram). The results demonstrate that the synergistic effects of co activation of D1 and D2 receptors observed after systemic administration are mediated at least in part by an interaction at the level of the striatum. Differences and similarities between the behaviors expressed after various treatments are discussed. PMID- 2574623 TI - Effects of acromelic acid A on the binding of [3H]glutamic acid and [3H]kainic acid to synaptic membranes and on the depolarization at the frog spinal cord. AB - Triton treatment of synaptic membranes from the frog spinal cord enhanced the specific binding of [3H]glutamic acid compared with non-treated fresh and frozen ones, but not that of [3H]kainic acid. Acromelic acid A specifically inhibited the binding of [3H]kainic acid, and was approximately 100 times more potent than kainic acid. Acromelic acid A and excitatory amino acids caused a depolarization in the ventral root of the frog spinal cord in a dose-dependent manner, and the effect of acromelic acid A was much superior to that of kainic acid or domoic acid. Acromelic acid A is one of the most potent kainic acid agonist at the frog spinal cord. PMID- 2574625 TI - [The incidence and clinical picture of hemorrhagic fever with renal syndrome in East Slovakia: the eastern and western type]. AB - Hemorrhagic Fever with renal syndrome (HFRS) is endemic in East Slovakia. The paper presents the clinical picture of 4 serologically confirmed cases. Two of the 4 patients had serological evidence of recent Hantaan virus infection. Positive immunofluorescent reactions with Puumala virus (CG 18-20) were detected in the sera of the other two patients. The obtained results suggest the circulation of two serotypes of HFRS in Slovakia. PMID- 2574624 TI - Activity dependent alkaline and acid transients in guinea pig hippocampal slices. AB - Changes of extracellular proton concentration ([H+]o) and K+ activity ([K+]o) were simultaneously measured by ion-sensitive microelectrodes in the CA3 region of guinea pig hippocampal slices. Repetitive electrical stimulation and application of glutamate or GABA were associated with prominent alkaline transients of up to 0.2 pH units lasting 2-10 s followed by smaller acid transients lasting up to 4 min. About 10-fold smaller alkaline transients were induced by spontaneous field discharges in the presence of bicuculline. The time to the maximal amplitude of the alkaline transients and the time to maximal increases of [K+]o were in the same range, concurring with the assumption that alkaline transients are due to a proton influx through cationic channels. However, spontaneous field discharges in low-calcium solution in which synaptic transmission is reduced were associated with acid transients of up to 0.02 pH units lasting 2-20 s. An alkaline transient was superimposed on the acid transient only when increases of [K+]o exceeded 1.5 mM. The effects of changing [H+]o on electrically evoked field potentials and spontaneous field discharges were studied in the range from pH 7.00 to 7.80. Electrically evoked field potentials were markedly depressed from pH 7.15 to 7.00 and enhanced from pH 7.60 to 7.80. The frequency of spontaneous field discharges in the presence of bicuculline significantly decreased by reducing pH from 7.40 to 7.30 and continuously increased from pH 7.40 to 7.80. In the same way, the frequency and the amplitude of spontaneous field discharges in low-calcium solution decreased from pH 7.40 to 7.15 and increased from pH 7.40 to 7.80.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574626 TI - Terfenadine with or without phenylpropanolamine in the treatment of seasonal allergic rhinitis. AB - The efficacy of terfenadine in combination with phenylpropanolamine was assessed by comparison with terfenadine alone in a double-blind, parallel group study of 66 patients with nasal birch pollen allergy. The patients were allocated randomly into two groups; 34 patients received terfenadine (60 mg) twice daily and 32 patients a combination tablet containing terfenadine (60 mg) and phenylpropanolamine (50 mg) twice daily for 17 days during the birch pollen season. Nasal symptoms (sneezing, discharge, itching and blockage) were relieved significantly by both drugs, but control of symptoms was more rapid and better with the terfenadine-phenylpropanolamine combination. Rhinoscopic evaluation of nasal secretion and mucosal swelling showed no differences between the treatment groups. Compared with pre-season values, nasal peak expiratory flow (PEF)-values worsened significantly during the season in the terfenadine, but not in the terfenadine-phenylpropanolamine, group. The general condition of the patients was significantly better in the terfenadine-phenylpropanolamine group. There were no marked side-effects in either group. At the end of the trial some of the patients in both treatment groups still had symptoms; this is apparently due to the long lasting and severe pollen season. It is concluded that terfenadine combined with phenylpropanolamine gives better control of seasonal allergic rhinitis than terfenadine alone. PMID- 2574627 TI - The effects of terfenadine with and without alcohol on an aspect of car driving performance. AB - Twelve healthy female volunteers received acute doses of terfenadine, 60 mg, 120 mg, 240 mg or placebo, followed by a 'social' dose of alcohol equivalent to 0.5 g absolute alcohol/kg body weight. Performance was assessed on laboratory analogues of car driving both before and after alcohol administration. Terfenadine (240 mg) was found to significantly impair performance alone and following alcohol. The results demonstrate the importance of establishing the behavioural effects of drugs over a range of doses. PMID- 2574628 TI - The effects of 4-aminopyridine and tetraethylammonium on the kinetics of transmitter release at the mammalian neuromuscular synapse. AB - The effect of 4-aminopyridine and tetraethylammonium on the time course of neurotransmitter release was examined at the neuromuscular junction using a computer-aided method which directly measured the time of occurrence of individual quanta. It is apparent that the action of 4-aminopyridine, at concentrations of 0.1 to 1 mM, when examined in isolation from other experimental manipulations, is to cause a greatly enhanced probability of release at times subsequent to the time over which the initial phase is essentially unchanged, i.e., there is no evidence of an increased latency of release caused by 4 aminopyridine. Similar results were obtained with tetraethylammonium, although the prolongation of release was much less, even at a concentration of 1 mM. The results are consistent with the view that the predominant action of 4 aminopyridine is to block the potassium conductance responsible for repolarization of the action potential and hence cause a prolonged Ca2+ current. The action of tetraethylammonium is consistent with the block of a different K+ conductance, with consequent enhancement of action potential effectiveness, but with little prolongation of release. The observation of multiple peaks, or oscillations in the release probability function at high (ca. 1 mM) concentrations of 4-aminopyridine, may be related, as is suggested, to oscillations of presynaptic membrane potential, or perhaps to changes in the electrochemical gradient for Ca2+ influx. PMID- 2574629 TI - Biochemical mechanisms of atrial natriuretic factor action. AB - Since atrial natriuretic factor (ANF) is a natriuretic and vasodilatory hormone, its mechanisms of action expectedly involve so-called negative pathways of cell stimulation, notably cyclic nucleotides. Indeed, the guanylate cyclase-cyclic GMP (cGMP) system appears to be the principal mediator of ANF's action. Specifically, particulate guanylate cyclase, a membrane glycoprotein, transmits ANF's effects, as opposed to the activation of soluble guanylate cyclase such agents as sodium nitroprusside. The stimulation of particulate guanylate cyclase by ANF manifests several characteristics. One of them is the functional irreversibility of stimulation with its apparent physiological consequences: the extended impact of ANF on diuresis and vasodilation in vivo lasts beyond the duration of increased plasma ANF levels and is accompanied by a prolonged elevation of cGMP. Another characteristic is the parallelism between guanylate cyclase stimulation and increases of cGMP in extracellular fluids. cGMP egression appears to be an active process, yet its physiological implications remain to be uncovered. In heart failure, cGMP continues to reflect augmented ANF levels, suggesting that in this disease, the lack of an ANF effect on sodium excretion is due to a defect distal to cGMP generation. In hypertension, where ANF levels are either normal or slightly elevated, probably secondary to high blood pressure, the ANF responsiveness of the particulate guanylate cyclase-cGMP system, the hypotensive effects, diuresis and natriuresis are exaggerated. The implications of this exaggerated responsiveness of the ANF-cGMP system in the pathophysiology of hypertension and its potential therapeutic connotations remain to be evaluated. PMID- 2574630 TI - Cancer patients' lymphocytes contain CD3+ CD4+ cells that proliferate in response to autologous tumor cells in the presence of exogenous low-dose interleukin-2 and autologous accessory cells. AB - To see whether cancer patients possess CD3+ CD4+ lymphocytes able to proliferate in response to autologous tumor cells (Auto-Tu), this lymphocyte subset was isolated either by positive or negative selection, both methods resulting in highly enriched CD4+ populations. Unseparated and isolated CD3+ CD4+ lymphocytes were then assayed for proliferating activity in the presence or absence of various amounts of Auto-Tu, with or without recombinant interleukin-2 (IL-2) (1.5 15 U/ml) and DR+ adherent cells or E- lymphocytes as autologous accessory cells (Auto-AC). Isolated CD3+ CD4+ lymphocytes were stimulated by Auto-Tu alone in only 1 out of 12 cases. CD3+ CD4+ cells failed to proliferate significantly in response to low doses of IL-2 alone but the addition of Auto-Tu caused stimulation in 8 out of 12 cases (67%). The further addition of Auto-AC to Auto Tu + IL-2 resulted in enhanced response of isolated CD3+ CD4+ lymphocytes in 6 out of 8 cases tested. When reactivities to Auto-Tu in the presence of IL-2 and IL-2 + Auto-AC were considered together, positive responses of CD3+ CD4+ lymphocytes were seen in 11 out of 12 cases (92%). On the other hand, unseparated lymphocytes were stimulated by Auto-Tu alone in none out of 12 cases. Unseparated lymphocytes, however, responded to IL-2 in 11 out of 12 cases; such a response was increased by the addition of Auto-Tu in only 2 cases. Moreover, the IL-2 proliferation of unseparated lymphocytes was suppressed in 4 and in 3 out of 12 cases tested when Auto-Tu or Auto-Tu + Auto-AC were added respectively. These data indicate that lymphocytes of cancer patients contain CD3+ CD4+ cells that are usually unable to proliferate in response to Auto-Tu only. This proliferation, however, occurs when low doses of exogenous IL-2 are present and can be further amplified by the addition of Auto-AC. No response of CD4+ cells is observed in the presence of DR+ Auto-AC + IL-2 except in 2 out of 7 cases tested (28%), suggesting an Auto-Tu-restricted reactivity of CD3+ CD4+ lymphocytes in the majority of cases. PMID- 2574631 TI - Which drug for what patient with heart failure, and when? AB - Congestive heart failure is emerging as an important public health problem because of its frequency and high mortality. Over the past decade, a number of clinical trials have been launched in a systematic attempt to determine an optimal therapeutic strategy for the treatment of heart failure. There appears to be a trend to begin treatment with both a diuretic and a vasodilator regimen in patients with symptomatic left ventricular dysfunction. Converting enzyme inhibitors have been shown to clearly benefit patients with class IV heart failure. The role of digitalis, other inotropic agents, beta-blockers, partial beta-agonists and antiarrhythmic agents is still evolving, but several clinical trials of these agents have been recently launched or are in the planning stages. Patients with symptomless left ventricular dysfunction are at risk to develop heart failure. One attractive hypothesis being tested is that preventive therapy with converting enzyme inhibitors may prevent progressive cardiac dilatation and thereby improve survival in this important reservoir of patients. Until the results of these numerous clinical trials are published, physicians should reserve judgement regarding the undefined efficacy of various investigational agents used in the treatment of heart failure and use their experience and judgement when planning a therapeutic strategy for their individual patients. PMID- 2574632 TI - Apparent lack of beta 2 adrenergic receptors in porcine myocardium. AB - The aim of this study was to investigate the relative numbers of myocardial beta 1 and beta 2 receptors in pigs. Membrane particles from left ventricular porcine and mixed ventricular rat myocardium were examined for subtypes of beta adrenergic receptors with a radioligand binding technique using [125I] cyanopindolol (ICYP) as trace, and the new highly beta 1 selective antagonist Sandoz 204 545 and the beta 2 selective antagonist ICI 118 551 for displacement. Radioligand displacement experiments were also performed using propranolol, isoprenaline and terbutaline. The displacement curves obtained with the subtype selective antagonists and agonist revealed biphasic inhibition of specific ICYP binding in rat preparations, indicating a beta 1/beta 2 ratio of approximately 2/1. In porcine preparations displacement of specific ICYP binding with all agents resulted in monophasic curves, thus sharply contrasting the rat preparations. Affinity constants of displacing drugs derived from these monophasic curves indicated that the specific binding site was a beta 1 receptor. No displacement compatible with beta 2 affinity was found. In the same rat preparations we found that adenylate cyclase activation and inhibition by beta receptor subtype specific agonists and antagonists were mediated by two receptor subtypes, whereas in the pig, adenylate cyclase activation and its inhibition seemed to occur via only one receptor subtype, the beta 1 adrenoceptor. PMID- 2574633 TI - An essential G1 function for cyclin-like proteins in yeast. AB - Cyclins were discovered in marine invertebrates based on their dramatic cell cycle periodicity. Recently, the products of three genes associated with cell cycle progression in S. cerevisiae were found to share limited homology with cyclins. Mutational elimination of the CLN1, CLN2, and DAF1/WHI1 products leads to cell cycle arrest independent of cell type, while expression of any one of the genes allows cell proliferation. Using strains where CLN1 was expressed conditionally, the essential function of Cln proteins was found to be limited to the G1 phase. Furthermore, the ability of the Cln proteins to carry out this function was found to decay rapidly upon cessation of Cln biosynthesis. The data are consistent with the hypothesis that Cln proteins activate the Cdc28 protein kinase, shown to be essential for the G1 to S phase transition in S. cerevisiae. Because of the apparent functional redundancy of these genes, DAF1/WHI1 has been renamed CLN3. PMID- 2574634 TI - Diagnosis, treatment, and rehabilitation of injuries to the lower leg and foot. AB - The article provides an overview of specific lower-extremity and foot injuries. The areas of concentration are sinus tarsi syndrome, tendon injuries, stress fractures, ankle sprains, and plantar fascitis. Diagnosis, treatment, and rehabilitation techniques have been discussed for each injury. The authors have also included biomechanical treatment modalities using orthotics for rehabilitation of these injuries. PMID- 2574635 TI - Sequence and transcript analysis of the C. albicans URA3 gene encoding orotidine 5'-phosphate decarboxylase. AB - The human pathogen Candida albicans grows either as a yeast or in filamentous form. We have determined the sequence of a 1.365 kb genomic C. albicans fragment that complements Saccharomyces cerevisiae ura3 and Escherichia coli pyrF mutations. An open reading frame within this fragment corresponds to a protein of 270 amino acids that shows homology to orotidine-5'-phosphate decarboxylases (ODCases) of other fungal species. The C. albicans ODCase is most closely related to the ODCases of the budding yeasts Kluyveromyces lactis and S. cerevisiae (74% and 71% homology, respectively). Most 5' ends of URA3 transcripts in the authentic host and in the heterologous host S. cerevisiae were found to be identical. These results demonstrate a close taxonomic relationship between non pathogenic budding yeasts and C. albicans. PMID- 2574636 TI - Characterization of transcribed dispersed repetitive DNAs in the nuclear genome of the green alga Chlamydomonas reinhardtii. AB - Four cDNAs (cDNAs 1-4), 162, 338, 321 and 167 bp in size, that contain repetitive DNA sequences, were isolated from C. reinhardtii. cDNAs 1, 2 and 3 hybridized to multiple transcripts in poly A+ RNA. Each of the four repeat families is comprised of an extremely heterogeneous population of interspersed nuclear DNA sequences most of which are less than 0.5 kbp in size. A large number of restriction fragment length polymorphisms were uncovered by using cDNAs 1 and 2 as hybridization probes. cDNA2 was compared to two different genomic DNA sequences: the first sequence was complementary to a central 136 bases of cDNA2, which is bordered by a 15-bp imperfect direct repeat; the second sequence lacks a poly-dA tail, but is otherwise colinear along its entire length with cDNA2. This suggests that some members of the cDNA2 repeat family contain signals for polyadenylation. The majority of accumulated transcripts that hybridize to cDNA2 have the same 5'-3' orientation as cDNA2. PMID- 2574637 TI - Induction of DNA double-strand breaks in Chinese hamster V79 cells by 2 chlorodeoxyadenosine. AB - 2-Chlorodeoxyadenosine was found to induce DNA double-strand breaks as well as cell death in log-phase Chinese hamster V79 cells. The induction of DNA double strand breaks, measured by a neutral elution technique, was observed after a 2-h incubation of the cells in the presence of 5 microM of 2-chlorodeoxyadenosine, but these breaks were almost rejoined by a subsequent 1-h incubation, even though this drug was present in the medium during incubation. This repair was prevented by the addition of nicotinamide, which is known to inhibit poly(ADP-ribose) synthesis that is strongly associated with the DNA ligation, but not prevented by the addition of 9-beta-D-arabinofuranosyladenine (araA), which is known to inhibit DNA polymerization. These results suggest that the repair of CdA-induced double-strand breaks is achieved by ligation alone without DNA polymerization. When 35 microM of cycloheximide and 1.3 mM of dibutyryl cAMP were added to the medium, it was found that the induction of double-strand breaks by 2 chlorodeoxyadenosine was suppressed, while the cytotoxicity of 2 chlorodeoxyadenosine measured by colony-forming ability was not interfered with. These results suggest that the induction of DNA double-strand breaks is not associated with the cytotoxicity of this drug. PMID- 2574638 TI - [Type II oculo-cutaneous tyrosinosis or Richner-Hanhart syndrome--apropos of a case]. PMID- 2574639 TI - Current status of calcium channel-blocking drugs after Q wave and non-Q wave myocardial infarction. AB - The calcium channel blockers are useful in treating many cardiovascular disorders. Due to their anti-ischemic and spasmolytic properties, the cardioprotective effects of these agents have been studied in the setting of acute myocardial infarction. This paper will review this application with respect to limitation of infarct size, reduction of mortality, and incident morbidity rates. Of the agents currently available for clinical use, nifedipine has been studied most extensively. This agent shows no beneficial effects and its use can, in fact, be harmful in this setting. Of the few trials that have been conducted with verapamil, none have shown a preventive effect on death, reinfarction, or postinfarction angina. Both verapamil and diltiazem might limit infarct size although further confirmation is required. At the present time, diltiazem is the only agent shown to have short- and long-term benefits on clinical outcome in patients with acute myocardial infarction. The success of prophylactic diltiazem is, however, critically dependent on proper patient selection. In particular, those patients with non-Q wave infarction, normal left ventricular function, or both can be expected to derive the greatest benefit in terms of reduced mortality and incident morbidity. PMID- 2574640 TI - Response of blood pressure, cardiac output, peripheral resistance, and exercise performance to substitution of calcium blocker for beta-blocker plus thiazide diuretic therapy in patients with both systemic hypertension and mild stable angina. AB - We studied 14 patients to determine whether sustained-release diltiazem is a satisfactory long-term substitute for the combination of propranolol plus hydrochlorothiazide (HCTZ), control phase, in the treatment of systemic hypertension with coexisting chronic stable angina pectoris. All patients had either one- or two-vessel coronary disease and normal left ventricular systolic function. Measurements were made during the control phase and 4 and 8 weeks after substitution of sustained-release diltiazem. Only the sitting blood pressure was available before the control phase (pretreatment). Blood pressure and heart rate were measured with patients supine, sitting, and 5 minutes after standing. Cardiac output was measured in the supine position using a computerized Doppler system, and stroke volume, mean arterial pressure, and total systemic resistance were calculated. Symptom-limited modified Bruce protocol treadmill tests were performed to determine time to onset of 1 mm ST segment depression, time to termination of exercise, reason for cessation of exercise, and maximum rate pressure product. The patients were initially receiving 160-240 mg/day of propranolol (40-60 mg q.i.d.) plus 25-50 mg/day of HCTZ and, subsequently, 12 of 14 had substitution with 240 mg/day (120 mg b.i.d.) of sustained-release diltiazem, and two received 360 mg/day with one of these patients also receiving 50 mg/day of HCTZ. These patients are a subset of a larger group of patients in whom the response of blood pressure alone has been previously reported. Diltiazem resulted in reduction of blood pressure equivalent to that with the propranolol plus HCTZ combination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574641 TI - Theoretical considerations in the use of calcium entry blockers in silent myocardial ischemia. AB - Asymptomatic myocardial ischemia likely results from an imbalance between myocardial oxygen supply and demand. Although changes in coronary vasomotor tone probably are important in the genesis of asymptomatic ischemia, heart rate increases also play a critical role. Consequently, all three classes of antianginal agents, nitrates, beta-blockers, and calcium entry blockers, have been shown efficacious as monotherapy for silent ischemia. Comparative studies have demonstrated that agents or combination therapies that control heart rate increases during normal activities are superior to regimens that increase average heart rate. Consideration of the side-effect profile of any therapy for asymptomatic patients also is important. The ideal therapy would be with one drug that reduced coronary vasomotor tone and myocardial oxygen demand during normal activities and had no adverse effects. Currently, the calcium entry blockers, diltiazem and verapamil, most closely approximate this ideal. It has yet to be proven, however, that the treatment of asymptomatic myocardial ischemia improves the prognosis of patients with coronary artery disease, and the risk-benefit ratio of pharmacological therapy is not established. PMID- 2574642 TI - Calcium antagonists in the treatment of Prinzmetal's angina and unstable angina pectoris. AB - Calcium antagonists block the entry of calcium into vascular smooth muscle cells, producing pharmacological vasodilation. Thus, it is not surprising that these drugs are effective in treating unstable angina that is often characterized by increased vasomotion and dynamic obstruction at the site of atheromatous plaques. Nifedipine, diltiazem, and verapamil are all highly and equally effective in reducing painful and painless ischemic episodes in Prinzmetal's variant angina. In patients with unstable angina who have known or suspected significant underlying coronary artery disease, a multipharmacological approach to therapy is warranted. Nifedipine used with beta-blocker drugs is more effective than nifedipine as monotherapy. Diltiazem and verapamil have been shown to be effective when given without beta-blockers in unstable angina patients. In many patients, thrombus formation rather than vasospasm is the major pathophysiological event resulting in progression of the syndrome to infarction or sudden death. In these patients, antiplatelet, antithrombotic, or antiplatelet and antithrombotic therapy is of utmost importance to maintain adequate coronary flow. Nonresponders to medical therapy with unstable angina have a high prevalence of eccentric and multiple coronary stenoses with a high incidence of thrombi. The best responders to calcium antagonist therapy are patients with concentric coronary stenoses. In summary, calcium antagonists are highly effective in reducing ischemic episodes in patients with Prinzmetal's angina and effective for therapy for unstable angina when used in conjunction with other forms of medical treatment aimed at the processes of platelet activation and thrombus formation. PMID- 2574643 TI - The sugar-chain heterogeneity of human gamma-glutamyl transferases from the reproductive system and kidney. AB - The sugar-chain heterogeneity of gamma-glutamyl transferase (gamma-GTP, EC 2.3.2.2) from the human reproductive system (seminal plasma, prostate and testis) and kidney was investigated using the serial lectin affinity technique and their properties were compared. According to the results of serial lectin affinity chromatography, a possible sugar chains of enzymes from reproductive system were mainly of the hybrid type without fucose linkages to the innermost GlcNAc and/or the biantennary complex type sugar chains and a few were of the multiantennary complex-type with branched GlcNAc (beta 1-4) Man and bisecting complex type sugar chains. On the contrary, the major sugar chains of kidney gamma-GTP were of the multiantennary complex type and/or bisecting complex type sugar chains. Results of isoelectric focusing showed the gamma-GTP bound multiantennary complex type sugar chains to be the most acidic glycoprotein. Moreover, the biantennary type sugar chains were slightly more acidic than the high mannose and/or hybrid type sugar chains, varying with the degree of sialylation. PMID- 2574644 TI - Serum F protein: a new sensitive and specific test of hepatocellular damage. AB - F protein is a 44-kDa protein which is found mostly in the liver and circulates at much lower concentrations in the serum. Serum F protein has been measured, using a recently developed radioimmunoassay, in a variety of diseases and was appreciably raised only in patients with hepatocellular damage. The serum F protein concentration was a more sensitive and specific marker of liver damage than conventional liver function tests and showed a close correlation with the histological assessment of liver damage (r = 0.86, P less than 0.001). This new marker may be of value in the diagnosis and treatment of liver disease. PMID- 2574645 TI - Reasons for the variability in growth hormone (GH) responses to GHRH challenge: the endogenous hypothalamic-somatotroph rhythm (HSR). AB - The aims of this study were: (1) to test the possibility that pre-GHRH plasma GH values could reflect the functional status of the hypothalamic-somatotroph rhythm (HSR) at testing, and thus explain if it is responsible for the marked variability in GH responsiveness to GHRH challenge and (2) to see if exogenous somatostatin (SS) could disrupt this endogenous HSR and thus make the GH responses homogeneous. (1) Two to 14 GHRH acute tests (GRF-29, 1 micrograms/kg, i.v. bolus) were performed in 12 normal men and 10 normal women at the same time (0830 h) at random intervals (2 to 60 days). Blood samples to measure plasma GH were drawn at 15 min intervals before and after GHRH challenge. Given that the increments in pre-GHRH plasma GH values (I = value at 0 min minus value at -15 min) were highly correlated with either GHRH-elicited peaks of GH (men, r = 0.81; women; r = 0.69; P less than 0.0001) or the rise in GH after the challenge (r = 0.685; P less than 0.0001, in the total of tests performed), three theoretical HSR phases were proposed: (A) I greater than or equal to 0.4 microgram/l Secretory Phase; (B) I less than or equal to 0, (from GH at -15 min greater than or equal to 1.5 microgram/l), Secretion Plateau; (C) I less than or equal to 0, (from GH at -15 min less than or equal to 1.5 microgram/l), Refractory Phase. Individually, 91% of the men and 86% of the women showed a constant HSR phase when tested at the same time of day independently of the intervals between tests. GH responses (peaks, mean +/- SEM, g/l) in Phase A (women, 51.5 +/- 4.1; men, 31.4 +/- 3.2) were significantly higher (P less than 0.01) than those in Phase B (women, 22.6 +/- 1.8; men, 19.7 +/- 1.5), and these than those in Phase C (women, 9.2 +/- 1.5; men, 6.2 +/- 0.5). The great dispersion observed when GH peaks were analysed as a whole disappeared (except in Phase A in women) when they were evaluated according to the HSR Phase at testing. (2) In seven men and eight women 7 min after stopping an infusion of SS (250 micrograms/h for 3 h) a new GHRH test was performed. Plasma GH variations prior to SS infusion expressed the previous HSR Phase, while the GHRH-elicited peak of GH established the Phase at the moment of testing.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2574646 TI - The half-life of exogenous growth hormone after suppression of endogenous growth hormone secretion with somatostatin. AB - We have estimated the half-life of serum growth hormone (GH) in six subjects on 14 occasions following an intravenous bolus injection of either 50 or 500 mU of biosynthetic human growth hormone (B-hGH) while endogenous GH secretion was suppressed by a continuous infusion of somatostatin. The disappearance curve of serum GH was mono-exponential and the mean half-life was 8.9 min (SD 1.5). This is less than previously reported and has important implications for the performance of GH profiles, which should be performed with 10-15 min sampling intervals, and the calculation of pituitary GH secretion rates. PMID- 2574647 TI - Hepatic microsomal enzyme induction and adrenal crisis due to o,p'DDD therapy for metastatic adrenocortical carcinoma. AB - Two cases are described in which metastatic adrenocortical carcinoma associated with Cushing's syndrome was treated with mitotane (o,p'DDD). The first patient had initially been treated by bilateral adrenalectomy and, whilst responding to mitotane biochemically and by remission of metastases, experienced repeated episodes of adrenal crisis requiring a substantial increase in steroid therapy. The second patient failed to respond to the drug, but evidence of hepatic enzyme induction was noted during its administration. It is suggested that hepatic microsomal enzyme induction can occur in association with treatment with mitotane and that this can lead to an increased destruction of exogenous steroid with clinical consequences. PMID- 2574648 TI - [The kinesiological, chemical and pathological analysis in pulsed magnetic stimulation to the brain]. AB - Pulsed magnetic stimulation of the human brain and spinal region has been reported recently. Unlike electrical stimulation, magnetic stimulation excites the motor cortex without discomfort to the subject. This method will be used as a new clinical test to study the central motor pathway. Although no deleterious effects have been observed thus far, the safety of this technique is regarded as unproven. We have investigated kinesiological, neurochemical and pathological analysis. Our pulsed magnetic discharge system consists of a high voltage capacitor bank and flat circular coil of insulated copper wire. The high voltage capacitor bank has a maximum voltage of 900 V, a maximum current flow of 8,000 amp and 1,637 uF in condenser capacitance. Sixty four normal wistar rats each weighing 200 g were used in this study. The rats were separated into two groups. Rats in one group received pulsed magnetic stimulation 50 times in 0.5 Hz by a flat circular coil which surrounded the head of rat at 1 cm in front of the interauricular line. The rats were housed in a long circular chamber. Rats in the other group did not receive the pulsed magnetic stimulation in the long circular chamber. The details of kinesiological analysis by Animex II measurement were described in an other paper (Act Neurologica Scandinavica 73; 352-358, 1986). The measurement of monoamines, dopamine (DA), homovalinic acid (HVA), noradrenaline (NA), and 5-hydroxytryptamine (5-HT), were made according to the Mefford's method 1 hour and 4 days after the magnetic stimulation. The analysis of the pathological state was also studied 1 hour and 4 days after the magnetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574649 TI - Reversal of benzodiazepine side effects with flumazenil. PMID- 2574650 TI - Comparative biochemistry of hepatic arylsulfatases from north and south American opossums. AB - 1. The Virginia opossum (Didelphis virginiana) possessed an arylsulfatase which had a relative molecular weight of 130 +/- 12 kDa, displayed anomalous kinetics, hydrolysed AA2S, and exhibited other properties of arylsulfatase A. No arylsulfatase B was found. 2. The arylsulfatase present in the gray short-tailed opossum (Monodelphis domestica) had a relative molecular weight of 56 +/- 4 kDa, exhibited linear kinetics, was inhibited by chloride, and possessed other characteristics of arylsulfatase B. No arylsulfatase A was found. 3. Arylsulfatases from both species occurred as multiple isozymes which were unaffected by neuraminidase or alkaline phosphatase treatment. PMID- 2574651 TI - Contact allergy to Tego 103G disinfectant in a deep-sea diver. PMID- 2574652 TI - Esmolol HCl. PMID- 2574653 TI - [Post-traumatic splinting with glass fibers: esthetic flexibility]. PMID- 2574654 TI - [Interhemispheric subdural empyema]. AB - Six cases of interhemispheric subdural empyema are reported. It is a rare disease due to different infections origins. All of them are under 24 years old. The characteristics symptoms of these cases were intracranial infection, increased ICP, cerebral falx syndrome and focal seizure. The specific appearances on the films of angiography and CT scan were discussed. It could be located these lesions exactly. The surgical treatments were continuous drainage though cranial burr hole or excision of abscess. All 6 cases are cured with no recurrence. PMID- 2574655 TI - Neurobiology of brain-gut interactions. Implications for ulcer disease. AB - Clinical and laboratory evidence indicates that the brain exerts major control on the gastrointestinal tract. Specific brain loci and circuits that send efferent viscerotropic projections to the gut have been described. A variety of aminergic and peptidergic neurotransmitters have been shown to occur along these cerebrogastrointestinal pathways and to influence motor and secretory functions of the gut. Some of the newly identified peptides have been shown to influence the development of gastroduodenal ulcers. Findings with thyrotropin-releasing hormone (TRH) indicate that this endogenous tripeptide induces a full spectrum of gut effects, prominent among which is production of gastric ulcers. By contrast, other peptides including beta-endorphin, neurotensin, and bombesin induce gut effects opposite to those of TRH, namely, inhibition of gastric acid and motility and prevention of experimental ulcers. These laboratory findings suggest that ulcer disease may represent a brain-driven event, which may be the result of a neurochemical imbalance within the brain. Further neurobiological research will generate additional data on brain-gut interactions and will probably disclose new information to explain certain functional and organic disorders of the gut. PMID- 2574656 TI - Clinical relapse of Crohn's disease under standardized conservative treatment and after excisional surgery. AB - The course of 205 patients with Crohn's disease at one gastroenterological center was studied in patients with conservative drug treatment or with operative management of their disease. The decision for one or the other treatment regimen was made by an interdisciplinary team of gastroenterologists and surgeons. Using life-table analysis the 205 patients showed a clinical relapse rate of 27% after two years and 38% after four years. Clinical relapse was defined by a Crohn's disease activity index (CDAI) over 150. We used a standardized drug regimen of salazosulfapyridin and prednisone; the indication for excisional surgery was limited strictly to life-threatening situations, absolute nonresponse to drug treatment, and severe intervisceral fistulae. The operated patients (N = 93) had a lower relapse rate than the patients treated conservatively (N = 112), 20% and 51%, respectively, after four years. There were considerably fewer relapses in Crohn's colitis patients who were operated upon than in conservatively treated patients (18% versus 67% after four years); the same was found for ileocolitis (20% vs 49% after four years), but there was no difference between the treatment groups in ileitis (25-30% relapses for both after four years). In addition the patients with Crohn's disease of the colon had a more favorable course after resection with respect to symptoms, clinical and laboratory findings, and CDAI in remission. This paper gives data only for surgery in severe clinical situations and does not give a rationale for earlier surgery. This problem should now be studied in a randomized trial. PMID- 2574657 TI - Effect of ursodeoxycholic acid in chronic hepatitis and primary biliary cirrhosis. AB - Clinical and experimental investigations have suggested that ursodeoxycholic acid (ursodiol) may have cytoprotective or choleretic action and therefore be beneficial in patients with intrahepatic cholestasis or chronic liver disease. In an open-label study, we treated 45 patients with chronic hepatitis with 300 mg of ursodiol three times daily for six months. At four months, gamma-glutamyl transpeptidase (gamma-GTP) and leucine aminopeptidase levels had decreased. SGOT and SGPT levels also decreased significantly. Evaluation of histologic changes has not yet been completed. No significant differences in improvement of liver function tests were found in a comparison with 19 historical controls. We also studied eight patients with primary biliary cirrhosis, treated for more than one and a half years with 600 mg of ursodiol per day. At one month, itching diminished in five patients who had pruritus. ALPase and gamma-GTP levels decreased significantly, and GOT and GPT levels were also reduced. IgM levels did not change, but the titer of antimitochondrial body decreased by half in two patients. Levels of glycoursodeoxycholic acid increased, and in three patients follow-up liver biopsy showed marked improvement. These preliminary results suggest that ursodiol is safe and effective for the treatment of chronic hepatitis and primary biliary cirrhosis, but a large-scale, controlled trial is needed. PMID- 2574658 TI - Human nidogen: complete amino acid sequence and structural domains deduced from cDNAs, and evidence for polymorphism of the gene. AB - Nidogen, a multifunctional glycoprotein, is an integral part of all basement membranes. In this study, human nidogen cDNAs were isolated and characterized from human placental and skin fibroblast cDNA libraries by hybridization with a mouse nidogen cDNA probe. Six overlapping clones covering 4.9 kb were characterized. The composite cDNA contained a 3,741-nucleotide open reading frame which coded for a 1,247-amino-acid peptide that included a hydrophobic signal sequence. The deduced amino acid sequence contains seven epidermal growth factor like cysteine-rich repeats, one possible tyrosine O-sulfation site, and a possible N-glycosylation site. The tripeptide sequence -Arg-Gly-Asp- (RGD), a potential cell attachment site, was also present. Human and mouse nidogen sequences were 84% homologous at the nucleotide level and 85% homologous at the deduced amino acid level. Southern blotting of human leukocyte DNA from 23 individuals indicated that nidogen probably is a single-copy gene and shows multiple restriction fragment length polymorphisms when cleaved with Eco RI, Pvu II, Taq I, and Msp I. In particular, digestions with Pvu II revealed polymorphism in four discrete DNA fragments, which could be discriminated by hybridizations with nidogen subclones. One of the polymorphisms revealed an allelic frequency of 0.52/0.48. Thus, human nidogen gene displays RFLPs which provide analytical tools to establish genetic linkage between the nidogen gene and a clinical phenotype. PMID- 2574659 TI - Drug inhibitors of RNA polymerase II transcription. AB - Transcription by RNA polymerase II occurs after formation of a transcription complex. This complex is assembled in stages by the interaction of transcription factors with the template and/or with each other. We report on the ability of six drugs to inhibit the assembly of the RNA polymerase II transcription complex. Assembly of the complex on the adenovirus major late promoter requires several transcription factors. The normal assembly process requires that the DNA first interact with TFIIA, then with TFIID, and finally with at least four additional transcription factors (one of which is RNA polymerase II). We observed that streptolydigin (10 micrograms/ml) inhibits association of ILA and IID, and at higher concentrations (100 micrograms/ml) inhibits that IIA/IID complex from binding to DNA. Streptovaricin (100 micrograms/ml) appears to inhibit the IIA/IID interaction with DNA and prevents reinitiation (at 500 micrograms/ml). Adriamycin (1 microgram/ml) inhibits the interaction of TFIID with the IIA/DNA complex and inhibits an additional event immediately prior to, or during, elongation. Daunorubicin may be an elongation inhibitor. Heparin at 10 micrograms/ml inhibits further assembly after the IIA/IID/DNA complex has formed, and at 100 micrograms/ml also inhibits a late event in the assembly process and blocks reinitiation. Rifamycin AF/013 (100 micrograms/ml) inhibits the early events necessary to form the IIA/IID/DNA complex and (at 10 micrograms/ml) an assembly event following formation of the IIA/IID/DNA complex. Therefore, these compounds should be useful as probes for further examination of the assembly process. PMID- 2574660 TI - Structure and expression of the human motilin gene. AB - The human motilin gene was isolated from a human genomic library and its structure was determined by restriction mapping and DNA sequence analysis. The gene consists of five exons separated by four introns spanning approximately 9 kb of genomic DNA. Exon I encodes the 5' untranslated portion of the motilin mRNA. Exons II and III encode the signal peptide and the 22-amino-acid motilin peptide; codons encoding the motilin moiety are split by an intron. The carboxy-terminal motilin-associated peptide (MAP) is largely encoded by Exons III and IV with the last two amino acids of the motilin precursor and the 3' untranslated region encoded by Exon V. Thus, the motilin gene has an unusual structure in which a small bioactive peptide is encoded on two distinct exons. Examination of the expression of the human and nonhuman primate motilin gene by Northern hybridization analysis indicates that it is expressed in a number of gastrointestinal and extragastrointestinal tissues. PMID- 2574661 TI - [P glycoprotein as a resistance marker in tumors]. PMID- 2574662 TI - XlHbox 8: a novel Xenopus homeo protein restricted to a narrow band of endoderm. AB - We report the isolation of a new homeobox gene from Xenopus laevis genomic DNA. The homeodomain sequence is highly diverged from the prototype Antennapedia sequence, and contains a unique histidine residue in the helix that binds to DNA. The homeodomain is followed by a 65 amino acid carboxyterminal domain, the longest found to date in any vertebrate homeobox gene. We have raised specific antibodies against an XlHbox 8-beta-gal fusion protein to determine the spatial and temporal expression of this gene. The nuclear protein first appears in a narrow band of the endoderm at stage 33 and develops into expression within the epithelial cells of the pancreatic anlagen and duodenum. Expression within the pancreatic epithelium persists into the adult frog. This unprecedented restriction to an anteroposterior band of the endoderm suggests that vertebrate homeobox genes might be involved in specifying positional information not only in the neuroectoderm and mesoderm, but also in the endoderm. Our data suggest that XlHbox 8 may therefore represent the first member of a new class of position dependent transcription factors affecting endodermal differentiation. PMID- 2574663 TI - Isolation of potential vertebrate limb-identity genes. AB - Forelimbs and hindlimbs of tetrapods have different morphological patterns. One plausible explanation for the difference is that the cells that give rise to the limbs differentially express genes which control their pattern of development. Amphibian limb regeneration is an excellent system to test this hypothesis, since the same ultimate morphology is attained in regeneration as through embryogenesis. Using a combination of homeobox probes and differential screening, I have isolated two newt genes which are differentially expressed in regenerating forelimbs and hindlimbs. One of these genes displays properties expected of a gene involved in controlling limb morphology, including expression in mesodermal tissue and constancy of expression upon transplantation. Based on sequence analysis, this gene appears to be homologous to a homeobox-containing gene previously isolated from frog and human libraries. PMID- 2574664 TI - Expression of an engrailed-related protein is induced in the anterior neural ectoderm of early Xenopus embryos. AB - We have used a monoclonal antibody directed against the C-terminus of the Drosophila invected homeodomain to detect a nuclear protein in brain cells of Xenopus laevis embryos. We refer to this antigen as the Xenopus EN protein. The EN protein is localized at midneurula stage to a band of cells in the anterior portion of the neural plate, on each side of the neural groove. Later in development, the expression coincides with the boundary of the midbrain and hindbrain, and persists at least to the swimming tadpole stage. These properties make the EN protein an excellent molecular marker for anterior neural structures. In embryos where inductive interactions between mesodermal and ectodermal tissues have been perturbed, the expression of the EN protein is altered; in embryos that have been anterodorsalized by LiCl treatment, the region that expresses the EN protein is expanded, but still well organized. In ventralized UV-irradiated embryos, the absence of the protein is correlated with the absence of anterior neural structures. In extreme exogastrulae, where the contacts between head mesoderm and prospective neurectoderm are lost, the EN protein is not expressed. PMID- 2574665 TI - Azelastine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. AB - Azelastine is an antiallergic agent which demonstrates histamine H1-receptor antagonist activity and also inhibits histamine release from mast cells following antigen and non-antigen stimuli. Azelastine antagonises histamine- and leukotriene-induced bronchospasm in animal studies and reduces airway responsiveness to inhaled antigen or distilled water, and exercise challenge. In comparative studies, orally administered azelastine in doses up to 4 mg/day consistently relieved symptoms in patients with seasonal or perennial rhinitis - comparable to inhaled sodium cromoglycate (cromolyn sodium) 80 mg/day, oral chlorpheniramine (chlorphenamine) and oral terfenadine 120 mg/day. In addition, azelastine administered as an intranasal spray was as effective as oral terfenadine 120 mg/day and intranasal budesonide 0.4 mg/day in alleviating symptoms of rhinitis. Azelastine is also a potent antiasthmatic agent which produces significant and long lasting bronchodilation in patients with bronchial asthma. The drug is superior to placebo and comparable to oral ketotifen 2 mg/day and sustained release theophylline 700 mg/day when administered as a twice daily oral 4 mg dose. Azelastine is generally well tolerated: the most common adverse effects are altered taste perception and drowsiness. Adverse effects are mild and transient and result in withdrawal of treatment in less than 2% of patients. In a comparative study oral azelastine 2 or 4 mg/day produced no more sedation than terfenadine 120 mg/day. Thus, barring unexpected findings with wider clinical use, azelastine offers an effective and well tolerated choice of treatment for patients with allergic rhinitis and/or bronchial asthma, which may be particularly beneficial in patients in whom inhaled drug treatment is contraindicated. PMID- 2574666 TI - Etched metal prostheses to retain severely traumatized teeth in function. AB - Acid-etch retained appliances of the Rochette and Maryland designs have proved valuable for the replacement of permanent anterior teeth in adolescents and adults. This article describes 2 patients for whom traumatized teeth of poor or "hopeless" prognosis were retained by splinting them to their neighbours with a Maryland-type etched cast framework. Appearance and function have been maintained over several years, while the need for extraction and the provision of a conventional fixed prosthesis has been delayed or avoided. PMID- 2574667 TI - Tissue distribution of the AMP-activated protein kinase, and lack of activation by cyclic-AMP-dependent protein kinase, studied using a specific and sensitive peptide assay. AB - 1. We have synthesized two peptides, one based on the exact sequence around the unique site (Ser79) for the AMP-activated protein kinase on rat acetyl-CoA carboxylase (SSMS peptide) and another in which the serine residue corresponding to the site for cyclic-AMP-dependent protein kinase (Ser77) was replaced by alanine (SAMS peptide). 2. Both peptides were phosphorylated with similar kinetics by the AMP-activated protein kinase, but only the SSMS peptide was a substrate for cyclic-AMP-dependent protein kinase. The SAMS peptide was not phosphorylated by any of five other purified protein kinases tested. 3. The Km of AMP-activated protein kinase for the SAMS peptide is higher than that for acetyl CoA carboxylase, but the Vmax for peptide phosphorylation is 2.5 times higher than that of its parent protein. This peptide therefore gives a convenient and sensitive assay for the AMP-activated protein kinase. 4. Acetyl-CoA-carboxylase kinase and peptide kinase activities copurify through six steps from a post mitochondrial supernatant of rat liver, showing that the SAMS peptide is a specific substrate for the AMP-activated protein kinase in this tissue. We could not demonstrate AMP-dependence of the kinase activity in crude preparations, apparently due to endogenous AMP remaining bound to the enzyme. However, 8 bromoadenosine 5-monophosphate (Br8AMP) is a partial agonist at the allosteric (AMP) site, and inhibition by 2 mM Br8AMP can be used to test that one is measuring the AMP-stimulated form of the kinase. 5. Using this approach, we have examined the kinase activity in nine different rat tissues, plus a mouse macrophage cell line, and find that there is a correlation between tissues expressing significant levels of peptide kinase activity and those active in the synthesis or storage of lipids. 6. We also use the peptide assay to show that cyclic AMP-dependent protein kinase does not activate purified AMP-activated protein kinase, and does not affect the activation of partially purified AMP activated protein kinase by endogenous kinase kinase. PMID- 2574668 TI - Solubilization of somatostatin receptors in hamster pancreatic beta cells. Characterization as a glycoprotein interacting with a GTP-binding protein. AB - Somatostatin receptors of plasma membranes from beta cells of hamster insulinoma were covalently labelled with 125I-[Leu8,D-Trp22,Tyr25]somatostatin-28 (125I somatostatin-28) and solubilized with the non-denaturing detergent Triton X-100. Analysis by SDS/PAGE and autoradiography revealed three specific 125I somatostatin-28 receptor complexes with similar molecular masses (228 kDa, 128 kDa and 45 kDa) to those previously identified [Cotroneo, P., Marie, J.-C. & Rosselin, G. (1988) Eur. J. Biochem. 174, 219-224]. The major labelled complex (128 kDa) was adsorbed to a wheat-germ-agglutinin agarose column and eluted by N acetylglucosamine. Also, the binding of 125I-somatostatin-28 to plasma membranes was specifically inhibited by the GTP analog, guanosine-5'-O-(3-thiotriphosphate) (GTP[S]) in a dose-dependent manner. Furthermore, when somatostatin-28 receptors were solubilized by Triton X-100 as a reversible complex with 125I-somatostatin 28, GTP[S] specifically dissociated the bound ligand to a larger extent from the soluble receptors than from the plasma-membrane-embedded receptors, the radioactivity remaining bound after 15 min at 37 degrees C being 30% and 83% respectively. After pertussis-toxin-induced [32P]ADP-ribosylation of pancreatic membranes, a 41-kDa [32P]ADP-ribose-labelled inhibitory guanine nucleotide binding protein coeluted with the 128-kDa and 45-kDa receptor complexes. The labelling of both receptor proteins was sensitive to GTP[S]. The labelling of the 228-kDa band was inconsistent. These results support the conclusion that beta cell somatostatin receptors can be solubilized as proteins of 128 kDa and 45 kDa. The major labeled species corresponds to the 128-kDa band and is a glycoprotein. The pancreatic membrane contains a 41-kDa GTP-binding protein that can complex with somatostatin receptors. PMID- 2574669 TI - Evolutionary relationships among aminotransferases. Tyrosine aminotransferase, histidinol-phosphate aminotransferase, and aspartate aminotransferase are homologous proteins. AB - A data base was compiled containing the amino acid sequences of 12 aspartate aminotransferases and 11 other aminotransferases. A comparison of these sequences by a standard alignment method confirmed the previously reported homology of all aspartate aminotransferases and Escherichia coli tyrosine aminotransferase. However, no significant similarity between these proteins and any of the other aminotransferases was detected. A more rigorous analysis, focusing on short sequence segments rather than the total polypeptide chain, revealed that rat tyrosine aminotransferase and Saccharomyces cerevisiae and Escherichia coli histidinol-phosphate aminotransferase share several homologous sequence segments with aspartate aminotransferases. For comparison of the complete sequences, a multiple sequence editor was developed to display the whole set of amino acid sequences in parallel on a single work-sheet. The editor allows gaps in individual sequences or a set of sequences to be introduced and thus facilitates their parallel analysis and alignment. Several clusters of invariant residues at corresponding positions in the amino acid sequences became evident, clearly establishing that the cytosolic and the mitochondrial isoenzyme of vertebrate aspartate aminotransferase, E. coli aspartate aminotransferase, rat and E. coli tyrosine aminotransferase, and S. cerevisiae and E. coli histidinol-phosphate aminotransferase are homologous proteins. Only 12 amino acid residues out of a total of about 400 proved to be invariant in all sequences compared; they are either involved in the binding of pyridoxal 5'-phosphate and the substrate, or appear to be essential for the conformation of the enzymes. PMID- 2574670 TI - Purification and properties of the 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (phenylalanine-inhibitable) of Saccharomyces cerevisiae. AB - The phenylalanine-inhibitable 3-deoxy-D-arabino-heptulosonate-7-phosphate (dHp1P) synthase from Saccharomyces cerevisiae has been purified to apparent homogeneity by a 1250-fold enrichment of the enzyme activity present in wild-type crude extracts, employing an overproducing strain. The estimated molecular mass of 42 kDa corresponds to the calculated molecular mass of 42.13 kDa deduced from the previously determined primary sequence. Gel filtration indicates that the active enzyme is a monomer. The enzyme is an Fe protein and is inactivated by EDTA in a reaction which is reversible by several bivalent metal ions. The Michaelis constant of the enzyme is 18 microM for phosphoenolpyruvate (P-pyruvate) and 130 microM for erythrose 4-phosphate (Ery4P) and the rate constant was calculated as 10 s-1. Inhibition by phenylalanine is competitive with respect to erythrose 4 phosphate and non-competitive to phosphoenolpyruvate, with a Ki of 10 microM. PMID- 2574671 TI - Myocardial uptake of meta-[123I]-iodobenzylguanidine [( 123I]-MIBG) in patients with myocardial infarct. AB - Meta-123I-iodobenzylguanidine (123I-MIBG), which is an analog of norepinephrine, can be used to evaluate the integrity and function of sympathetic nerve endings in the heart. Myocardial uptake of 123I-MIBG was studied in 30 myocardial infarction patients and compared with the distribution of blood flow assessed with 201Tl. It was found that when a cold defect appeared on the 201Tl scintigram, its localization was identical to the cold defect on the 123I-MIBG scintigram. On the other hand, in three cases, a defect was found on the 123I MIBG scintigram, corresponding to the electrocardiographic localization of the infarct, whereas the 201Tl scintigram was normal. Most strikingly, the present study shows that drugs (antagonists of the adrenergic receptors, calcium antagonists, amiodarone) decrease or even abolish (as in the case of labetalol) myocardial uptake of 123I-MIBG. Consequently, any interpretation of the 123I-MIBG scintigram must take into account the treatment administered. PMID- 2574672 TI - Benzodiazepine prescriptions and therapist non-compliance. AB - In an investigation of benzodiazepine (BDZ) prescription patterns, psychiatrists in private practice were found to exhibit "therapist non-compliance" with regard to general medical recommendations for BDZ use. The findings indicate that BDZ prescriptions in general (53% among patients treated with psychotropics) as well as long-term treatment of patients (37%) are quite common among private practice psychiatrists. BDZ treatment is not restricted to "minor psychiatric disorders", and contrary to the guidelines, even patients with substance dependence are not excluded. A positive association was found for BDZ use and patients' self reported symptoms and health complaints, the number of other medications prescribed and age. In a discussion of therapist non-compliance it is proposed that this may be a consequence of a symptom-based treatment model, individual health concepts, the doctor-patient relationship and physician's cost-benefit analysis. Thus, psychiatrists' non-compliance may reflect to some extent a case oriented treatment rationale. PMID- 2574673 TI - Effect of urinary pH on the plasma and urinary kinetics of remoxipride in man. AB - The influence of urinary pH on the plasma and urinary kinetics of remoxipride in man has been studied in an open crossover trial in ten healthy male volunteers. Ammonium chloride (urinary pH 5.2) and sodium hydrogen carbonate (urinary pH 7.8) were used as pretreatments on two occasions in randomized order. On each occasion remoxipride 50 mg solution was administered orally and plasma and urinary concentrations of the drug were determined by HPLC and plasma prolactin concentrations by RIA. Remoxipride was rapidly distributed in the body according to a one-compartment model. The mean plasma elimination half-life (t1/2) was 3.6 h in the ammonium chloride experiment and 6.2 h in the sodium hydrogen carbonate experiment. The mean plasma clearance of remoxipride was 141 and 89.9 ml.min-1 in the acidic and alkaline conditions, respectively, and the corresponding mean renal clearances were 58.5 ml.min-1 and 11.7 ml.min-1. The urinary excretion of remoxipride up to 72 h after drug administration was 43.1% and 12.3% following acidification and alkalinization, respectively. Remoxipride induced a similar rapid, transient elevation of plasma prolactin under both conditions. Thus, the urinary pH has a marked effect on the elimination kinetics of remoxipride. After an overdose, treatment with ammonium chloride might be valuable in hastening elimination of remoxipride from the body. PMID- 2574674 TI - Interaction study of fenoldopam--digoxin in congestive heart failure. AB - The potential interaction between fenoldopam, a DA1 selective agonist, and digoxin has been studied in 10 patients with heart failure (NYHA Class II or III) on chronic digoxin treatment. Plasma levels and urinary recovery of the glycoside were monitored for 24 h before and after 9 days of treatment with fenoldopam 100 mg tid. Fenoldopam caused a small, non-significant decrease in the mean steady state plasma concentration and area under the plasma concentration curve of digoxin. As the clearance of digoxin was unchanged there does not appear to be an interaction between fenoldopam and digoxin at the level of the renal tubule. PMID- 2574675 TI - Intragastric and intraoesophageal pH monitoring in duodenal ulcerpatients: effect of the new histamine H2-receptor antagonist ramixotidine. AB - The effect of the new histamine H2-receptor antagonist ramixotidine 750 mg p.o., administered at 22.00 h, on intragastric and intraoesophageal pH monitored from 22.00 h to 08.00 h, was studied in a double-blind cross-over trial in 11 duodenal ulcer patients. Placebo and ramixotidine were given to each patient on 2 consecutive days in a randomized sequence. Three patients were excluded from the intragastric pH analysis as the records on the second study day were technically inadequate. No significant carry-over or sequence effect was noted. Intragastric hydrogen ion activity was significantly lower (p = 0.01) after ramixotidine than after placebo: median (range) 24 (9-100) vs 97 (27-188) mmol/l. The percentage of time with intraoesophageal pH less than 4 was less than 5% in all but three recordings, with a maximum value of 12%, and it was not significantly different after the two treatments. PMID- 2574677 TI - Factor requirements for activation and proliferation steps of human CD2+CD3-CD4 CD8- early thymocytes. AB - Human CD2+CD3-CD4-CD8- thymocytes were shown to display high in vitro growth ability although their factor requirements for activation and proliferation are not fully known. We have thus isolated these precursors and assayed their activation and proliferation potentials in response to various factors. Our results indicate that these cells proliferate in response to phytohemagglutinin (PHA), recombinant interleukin 2 (rIL 2) and rIL 4. Simultaneous addition of anti CD2I + III monoclonal antibodies (mAb) and rIL 2 highly increased cell growth while IL 4-induced proliferation was not enhanced upon addition of anti-CD2. Anti CD2 and PHA, but not IL 2, induced intracytoplasmic Ca2+ influx phosphatidyl inositol turnover as well as IL 2 receptor expression. Sequential studies indicated that CD2 triggering enable many more CD2+ precursors to respond to rIL 2. Endogenous IL 2 synthesis was necessary for PHA-induced cell growth. Neither of these in vitro treatment were able to induce membrane expression of CD3, CD4 or CD8 on CD2+ cells. PMID- 2574676 TI - The effect of angiotensin converting enzyme inhibitors (ACE-I) and selective beta 1-antagonists on bronchial reactivity and the cough reflex in man. AB - The non-specific bronchial reactivity and cough threshold of hypertensive patients on an ACE-I monotherapy regimen (either captopril or enalapril), a beta 1-antagonist monotherapy regimen (either atenolol or metoprolol) or a combination of an ACE-I with a beta 1-antagonist were determined in the present study. Forty six hypertensives who were on these medications performed a histamine inhalation test (to assess bronchial reactivity) and a further 36 of these individuals participated in the citric acid test (to assess cough threshold). A control cohort consisting of 25 age-matched, drug-free subjects also performed the citric acid test. The incidence of bronchial hyperreactivity was not significantly different between the ACE-I monotherapy regimen and the beta 1-antagonist monotherapy regimen (Chi-squared = 0.248). However, when the monotherapy regimens were pooled and compared with the ACE-I and beta 1-antagonist combination regimen, the combination regimen was found to be associated with a significantly higher incidence of bronchial hyperreactivity (Chi-squared = 6.69). No difference was observed between the age-matched controls and the hypertensive patients in terms of their cough threshold. PMID- 2574678 TI - Extra-thymic immature T cells: development in polyoma virus-induced murine salivary gland tumors. AB - Lymphocyte infiltrates which occur in some polyoma virus-induced murine salivary epithelial tumors are characterized. The lymphocytic infiltrates within the salivary tumors resemble cortical thymocytes with the phenotype PNA+, Thy-1.2 bright, Ly-2+L3T4+, Ly-1 dim, H-2Kdim, KJ16-133-. The salivary lymphocytes showed proliferation based on analysis of RNA and DNA content. Because thymocytes lose the immature phenotype before leaving the thymus, we propose that the salivary tumor infiltrates result from the intra-tumoral differentiation of blood-derived prothymocytes into "cortical thymocytes". Histologic examination of the salivary tumors indicates expression of class II major histocompatibility antigen on the tumor epithelium which may be essential in establishing the extra-thymic T lymphocyte-inductive microenvironment within the tumor. PMID- 2574680 TI - High- and low-affinity receptors for murine interleukin 6. Distinct distribution on B and T cells. AB - The distribution of the murine receptor for interleukin (IL) 6 was examined on a variety of cells. Binding sites for IL 6 were found on many cell lines including fibroblasts and bone marrow-derived macrophages. The highest density of binding sites was found on B cell hybridomas and plasmacytomas, irrespective of their IL 6 dependence for growth. Scatchard analysis carried out with these cells identified about 1000 high-affinity sites (Kd = 25 pM) and 10,000 low-affinity sites (Kd = 2.5 nM). The binding was specific for IL 6 and led to the internalization of the ligand. Receptors for IL 6 were also present on other B cell lines, but binding on normal resting or activated B cells was below the limit of detection (less than 3 molecules/cell). In contrast, receptors were found on mature thymocytes and on peripheral T cells. However, unlike plasmacytomas and hybridomas, T cells expressed only high-affinity binding sites. The difference in the relative numbers of high- and low-affinity receptors on different cells suggests that IL 6 interacts with several proteins, the expression of which varies from one cell type to another. PMID- 2574679 TI - Selective induction of growth factor production and growth factor receptor expression by different signals to a single T cell. AB - Stimulation of lymphokine production and the expression of receptors for growth factors can be dissociated in AK-8, a line of CD4+, I-A-restricted, conalbumin specific mouse T cells. When activated by antibodies specific for the T cell receptor (TcR; F23.1) or the CD3 complex (145-2C11) adsorbed to plastic culture wells, AK-8 cells produce lymphokines but are unable to proliferate. Proliferation takes place using the same stimuli upon addition of interleukin 1 (IL 1). Autocrine growth induced by anti-TcR, anti-CD3 or by antigen is dependent on IL 4 and not on IL 2 in this cell line, as shown by the effect of antibodies against IL 4 or the IL 2 receptor. Similarly to plastic-adsorbed antibodies, phorbol myristic acetate (PMA) or a combination of PMA and the calcium ionophore Ionomycin also induces secretion of growth factors without inducing proliferation, but in this case addition of IL 1 is ineffective in inducing AK-8 proliferation. When incubated with anti-TcR or anti-CD3 antibodies in soluble form these cells neither proliferate nor produce IL 4 even in the presence of IL 1. However, soluble antibodies in the presence of IL 1 induce enhanced expression of IL 2 receptors, as measured both by induction of responsiveness to exogenous IL 2 or flow cytometry analysis using anti-IL 2 receptor antibodies. These results show that the pathways for the activation of growth factor receptor expression and the induction of lymphokine secretion can be differentiated in this cell line using anti-TcR or anti-CD3 reagents in different physical forms. The transmembrane signals delivered by these different forms of anti-receptor antibody may allow an understanding of these distinct requirements for T cell growth. PMID- 2574681 TI - Genetic analysis of new restriction fragment length polymorphisms (RFLP) in the human IgH constant gene locus. AB - The human immunoglobulin heavy chain constant gene locus (IGHC) is polymorphic at both the protein (Gm and A2m allotypes) and the DNA level [RFLP for the gamma genes (IGHG), the switch mu region (IGHSM) and the switch alpha regions (IGHSA)]. The polymorphisms have been a valuable tool for assessment of the IGHC locus organization and a variety of population genetics and immunological investigations. In this study three new probes, identifying regions related to the IGHG (IGHPG and IGHSG) or IGHA (IGHAT) genes, have been employed to describe 11 different loci, 6 of which were polymorphic. Most of the polymorphisms are probably due to short insertions/deletions, particularly the SG regions, due to their repetitive structure. Ten loci were assigned to the IGHC region on the basis of known restriction maps, deletion mapping and association with mapped RFLP; the 11th, despite a striking sequence similarity with the IGHPG regions, could not be assigned to any known IGHC subregion. Analysis of these and previously known IGHG RFLP in a sample of 65 unrelated subjects plus 15 families allowed us to draw a genetic map, with particularly high resolution in the GP-G2 G4 genes region, revealing a marked discontinuity in the linkage disequilibrium values between pairs of adjacent loci. PMID- 2574682 TI - Human IGHC locus restriction fragment length polymorphisms in IgG4 deficiency: evidence for a structural IGHC defect. AB - In man, IgG4 is the least abundant of the four IgG subclasses, and its serum levels vary considerably from one subject to another. Its deficiency has been thought to lead to recurrent infections; nevertheless, it is also commonly found in healthy individuals (1/400 in the Italian population). In 39 subjects with IgG4 serum levels less than 1 microgram/ml, we used 4 different probes (described in the accompanying study, Bottaro et al., Eur. J. Immunol. 1989. 19: 2151) to examine 13 loci within the IGHC region and analyzed the RFLP for 7 of them. No aberrant restriction patterns were identified in any of the subjects, showing the absence of major IGHC structural alterations. The allele frequency of some loci, however, was significantly different from that of a control group of 95 random subjects. This variation was shown to depend on a selective increase in the number of homozygotes for the associated alleles, that reached significant levels for the IGHGP, G2, PG2, PG4 and SG4 loci, but not for SG1 and A2T. The highest value was reached for alleles in the PG4 region, just 5' of SG4. These data indicate that a minor structural IGHC defect is probably the cause of a significant fraction of IgG4 deficiencies. Moreover, the different association levels of the PG4 and SG4 regions suggest that this defect is likely to lie in an upstream regulatory region rather than in the structural G4 gene. PMID- 2574683 TI - TCGF III/P40 is produced by naive murine CD4+ T cells but is not a general T cell growth factor. AB - Several antigen-specific T cell lines were found to secrete a lymphokine upon activation by antigen or lectin that was provisionally termed T cell growth factor III (TCGF III) because it induced the proliferation of a CD4+ T cell clone independently from IL2 and IL4. Amino acid sequence analysis (and the functional properties of TCGF III) revealed that TCGF III was identical with a recently identified lymphokine termed P40. TCGF III/P40 was not only produced by long-term cultured T cell lines but also upon stimulation of freshly isolated Mlsa-reactive T cells. In addition, naive CD4+ T cells secreted TCGF III/P40 upon activation by lectin or allo-major histocompatibility complex structures. However, in spite of its growth-promoting activity for a CD4+ T cell clone this lymphokine does not appear to function as a general growth factor for T cells. PMID- 2574684 TI - Effects of 5-HT1A receptor agonists and NMDA receptor antagonists in the social interaction test and the elevated plus maze. AB - The effects of several 5-HT1A agonists and excitatory amino acid antagonists were compared to the standard benzodiazepines, diazepam and chlordiazepoxide (CDP) in two assays predictive of anxiolytic activity, the social interaction and elevated plus maze procedures. Indicative of anxiolytic effects the 5-HT1A agonists, buspirone, gepirone and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) all significantly increased social interaction time and open arm exploration time in the social interaction and elevated plus maze procedures, respectively. Likewise, anxiolytic activity in these assays were also produced by the competitive N methyl-D-aspartate (NMDA) antagonists, 2-amino-5-phosphonovaleric acid (AP-5), 2 amino-7-phosphonoheptanoic acid (AP-7), 3-(2-carboxypiperazin-4-yl)-propyl-1 phosphonic acid (CPP) and the non-competitive NMDA antagonist, (+)-5-methyl-10,11 dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) while NMDA produced anxiogenic effects. Furthermore, the anxiolytic effects of these agents were of equal magnitude to the benzodiazepines. These two classes of compounds were differentiated in the yohimbine-induced seizure assay, with the NMDA antagonists dose dependently antagonizing seizures similar to the benzodiazepines while the 5 HT1A agonists were inactive. These results suggest that the 5-HT1A agonists and the NMDA antagonists may be potential non-classical anxiolytic agents with different mechanisms of action. PMID- 2574685 TI - (+/-)-3,4-Methylenedioxymethamphetamine-induced changes in the basal activity and pharmacological responsiveness of nigrostriatal dopamine neurons. AB - The present study examined the effects of methylenedioxymethamphetamine (MDMA) on the basal activity and pharmacological responsiveness of rat nigrostriatal dopamine (DA) neurons. Under standard in vivo extracellular single-unit recording conditions, acute MDMA administered alone (i.v.) inhibited the firing rate of nigrostriatal DA neurons in a dose-dependent fashion. The potency of MDMA to elicit this inhibition was significantly reduced following depletion of either serotonin or DA. Acute MDMA pretreatments (10 mg/kg i.v., 90 s) also profoundly enhanced the sensitivity of nigrostriatal DA neurons to the rate-inhibitory effects of the D-2 DA receptor agonist quinpirole but not apomorphine. It has previously been demonstrated that the ability of quinpirole and apomorphine to inhibit nigrostriatal DA neuronal activity is dependent on the basal firing rate of the cell. Both acute MDMA and a single dose of MDMA (15 mg/kg i.p.) one week prior eliminated the rate dependency of quinpirole- and apomorphine-induced inhibition of the firing rate of these cells. These data suggest that, although MDMA is known to be a serotonergic neurotoxin, this compound may also exert direct functional effects on the nigrostriatal DA system. PMID- 2574686 TI - 3,4-Diaminopyridine-induced noradrenaline release from CNS tissue as a model for action potential-evoked transmitter release: effects of phorbol ester. AB - We used rabbit hippocampus slices preincubated with [3H]noradrenaline (NA) and applied short pulses of 3,4-diaminopyridine (3,4-DAP) during superfusion to investigate the mechanism underlying the 3H overflow evoked by 3,4-DAP and the effects of the protein kinase C (PKC) activator, 4 beta-phorbol 12,13-dibutyrate (PDB), in this model. The 3H overflow evoked by 200 microM 3,4-DAP (about 4-5% of tissue-tritium) was largely Ca2+-dependent, tetrodotoxin-sensitive and markedly reduced by clonidine, but it was enhanced by yohimbine. We also demonstrated that the response could be inhibited via presynaptic adenosine (A1-) and opioid (kappa ) receptors. PDB (1 microM) markedly increased the 3,4-DAP-evoked 3H overflow, its effect being almost unchanged following activation of presynaptic alpha 2-, A1- or kappa-receptors. Inhibitors of PKC (polymyxin B, staurosporine) almost abolished the 3,4-DAP-evoked 3H overflow and antagonized the effects of PDB. It is concluded that application of 3,4-DAP (200 microM for 2 min) to brain slices leads to depolarization of the neuronal membrane, Na+ current-carried action potentials, Ca2+ influx and the exocytotic release of NA, which in many aspects resembles the release evoked by electrical field stimulation. The findings with phorbol ester further support the involvement of PKC in transmitter release. Activation of PKC apparently does not directly interfere with signal transduction mechanisms of presynaptic inhibitory receptors on noradrenergic nerve terminals. PMID- 2574687 TI - Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine reduces the release of [3H]dopamine from rat striatal slices. AB - The systemic administration of 1-methyl-4-phenyl-1,2,3-6-tetrahydropyridine (MPTP) is neurotoxic to cerebral dopaminergic neurones in several animals species and can cause parkinsonism in man. The mechanism of action may involve the oxidation of MPTP in the brain to a pyridinium species, 1-methyl-4-phenylpyridine (MPP+). Systemic administration of MPTP in rats leads to little permanent damage. However, the stimulable release of 3H-labelled stores of dopamine from the rat striatum is transiently reduced by MPTP administration, with a concomitant reduction in the striatal dopamine receptor complement. No changes in acetylcholine release or modulation by dopamine receptors of either transmitter could be measured. The transient changes in dopamine release may provide a valuable insight into the plasticity of the nervous system and its recovery from neurotoxic insult. PMID- 2574688 TI - Effects of beta-agonist and antagonist on the pulmonary circulation and the pulmonary pressor response to 5-HT. AB - We investigated the effects of beta-agonist and antagonist (isoproterenol, propranolol) on the pulmonary circulation and on the pulmonary pressor response to 5-HT in an isolated canine lung lobe. The pulmonary vessels were dilated by isoproterenol at doses up to 200 micrograms, but were constricted by alpha adrenoceptor stimulation at relatively high doses. The mechanism by which isoproterenol inhibited the 5-HT response is probably related to the stimulation of beta-adrenoceptors at the lower doses and to the stimulation of alpha adrenoceptors at the higher doses. Propranolol alone had no effect on pulmonary vascular tone, but inhibited the 5-HT response markedly at doses high, possibly by directly blocking the 5-HT receptors. PMID- 2574689 TI - Effects of the selective dopamine D-2 receptor agonist, quinpirole on sleep and wakefulness in the rat. AB - The effects of the dopamine D-2 receptor agonist, quinpirole, were compared with those produced by dopamine D-2 antagonist, YM-09151-2, in rats implanted with electrodes for chronic sleep recordings. Quinpirole (0.015-1.0 mg/kg) induced biphasic effects such that low doses decreased wakefulness and increased sleep, while higher doses induced the opposite effects. At 0.015 mg/kg, YM-09151-2 slightly augmented wakefulness, while at 1.0-2.0 mg/kg it significantly increased light sleep but depressed REM sleep. Pretreatment with YM-09151-2 in a dose which preferentially acts at presynaptic sites reversed the suppressant effects of a low dose of quinpirole on wakefulness and slow wave sleep. In contrast, the administration of YM-09151-2 in a dose which blocks postsynaptic D-2 receptors prevented the effect of a high dose of quinpirole on wakefulness and slow wave sleep; the depression of REM sleep was not affected. The opposite effects observed on the waking EEG after activation of either dopamine autoreceptors or postsynaptic D-2 receptors with adequate doses of quinpirole tend to indicate an active role for DA in the control of the waking state. PMID- 2574691 TI - [Clinical pharmacology of beta-adrenoblockaders]. AB - The latest data on pharmacokinetics, pharmacodynamics and side effects of beta adrenoblockers are presented. Based on the data, the indications and contraindications for the use of beta-adrenoblockers in clinical practice are determined. PMID- 2574692 TI - Onset of transcription of the aminopeptidase N (leukemia antigen CD 13) gene at the crypt/villus transition zone during rabbit enterocyte differentiation. AB - The sequence of a cDNA clone (2.82 kbp) of rabbit intestinal aminopeptidase N (CD 13) is reported. Using the corresponding anti-sense RNA probe, the distribution of aminopeptidase N mRNA along the crypt/villus axis of the rabbit small intestine was studied by in situ hybridization. The aminopeptidase N gene is expressed along the whole length of the villus with a maximum at its base. Expression was not detected in the crypt cells. The distribution of aminopeptidase N mRNA correlates with the presence of active enzyme as monitored by histochemical staining. The results are compatible with onset of transcription of the aminopeptidase N gene at the crypt/villus transition zone during the enterocyte differentiation. PMID- 2574690 TI - GABA, glycine, glutamate, aspartate and taurine in the perihypoglossal nuclei: an immunocytochemical investigation in the cat with particular reference to the issue of amino acid colocalization. AB - The differential distribution of glutamate (Glu), aspartate (Asp), glycine (Gly), gamma-aminobutyric acid (GABA) and taurine (Tau) was investigated in the cat's perihypoglossal nuclei. Serial semi-thin (0.5 micron) sections through the perihypoglossal nuclei were incubated with antisera raised against the mentioned amino acids with the aim of studying possible co-localization. In each experiment different measures were undertaken in order to screen for possible cross reactivities, and all sections were processed together with test conjugates in order to ascertain the specificity of the antisera used. A very high proportion of the neurons in the perihypoglossal nuclei (about 90%) shows strong immunostaining for Asp and also displays distinct immunoreactivity for Glu in neighbouring sections. About 25% of the cells in the perihypoglossal nuclei are intensely immunostained for Gly, but very few cells show immunoreactivity for GABA. Only glial cells appear to be immunostained for Tau. Neurons that are Gly(+) also display Glu and Asp immunoreactivities. The neuropil of the perihypoglossal nuclei shows a high density of GABA(+), Gly(+) and Glu(+) puncta mainly representing stained axons and terminals. Fewer Asp(+) puncta and very few Tau(+) nerve terminal-like puncta are seen. Details of the regional distribution of immunopositive neurons and puncta within the perihypoglossal nuclei are described. The findings are discussed with particular reference to the possible role of the mentioned amino acids as transmitter substances in the known synaptic circuitry of the perihypoglossal nuclei. PMID- 2574693 TI - Vagotomy for duodenal ulcer resistant to H2-receptor antagonists. AB - One hundred and twenty-seven male patients were subjected to antiulcer surgery for duodenal ulcer resistant to H2-receptor antagonist treatment. Fifty-four (group A) had been on conservative treatment for up to 6 months, while the remaining 73 (group B) had been on conservative treatment for more than 6 and up to 20 months. Of the group A, 43 underwent truncal vagotomy with pyloroplasty (group A1) and 11 highly selective vagotomy (group A2). Of group B, 52 underwent truncal vagotomy with pyloroplasty (group B1) and 21 highly selective vagotomy (group B2). Follow-up ranged between 18 and 72 months (mean 37 months). There were one ulcer recurrence in group A1, none in group A2, nine in group B1 and five in group B2, the difference between group A and group B being statistically significant (p less than 0.05). There was significantly higher nonulcer associated morbidity after truncal than after highly selective vagotomy (p less than 0.05). No significant difference in the degree of peak acid output reduction was observed between the patients with and those without ulcer recurrence. These findings show that the administration of H2-receptor antagonists for more than 6 months in duodenal ulcer patients who, however, fail to have their ulcer healed is associated with high recurrence rate after vagotomy. It is suggested that such patients should undergo vagotomy as soon as they fulfill the criteria of resistance to H2-receptor antagonists. If conservative treatment has lasted for more than 6 months, vagotomy plus antrectomy has to be considered as the surgical treatment for these patients, with the possible cost of higher nonulcer associated morbidity. PMID- 2574694 TI - Antigenic homology within human enterotoxigenic Escherichia coli fimbrial colonization factor antigens: CFA/I, coli-surface-associated antigens (CS)1, CS2, CS4 and CS17. AB - Immunoglobulins, prepared from polyclonal rabbit antisera raised against Escherichia coli fimbrial antigens, colonization factor antigen (CFA)/I, and coli surface-associated antigens (CS)1, CS2 and CS4, were used to assess antigenic cross-reactions between these four fimbrial types by Western immunoblotting. Antibodies in a serum, prepared against CS4, cross-reacted strongly with the fimbrial subunits of CFA/I, CS1 and CS2. Antibodies in sera prepared against CFA/I and CS1 gave weak reactions with CS1 or CFA/I respectively and also with CS2 and CS4, while the antiserum prepared against CS2 did not react. CS4 antiserum also reacted with the CS17 fimbrial subunit, but not with the subunits of fimbrial antigens: CFA/III, CS5, putative colonization factor (PCF) 0159:H4 or PCF0166. PMID- 2574695 TI - The molecular genetics of differentiation. PMID- 2574696 TI - The abnormal oocyte phenotype is correlated with the presence of blood transposon in Drosophila melanogaster. AB - The abnormal oocyte mutation (2;44) originates in the wild: it confers no visible phenotype on homozygous abo males or females, but homozygous abo females produce defective eggs and the probability of their developing into adults is much lower than that of heterozygous sister females. We isolated by chromosome walking 200 kb of DNA from region 32. This paper reports that a restriction enzyme site polymorphism analysis in wild type and mutant stocks allowed us to identify a DNA rearrangement present only in stocks carrying the abo mutation. The rearrangement is caused by a DNA insert on the abo chromosome in region 32E which, by restriction map and sequence analysis, was identified as copia-like blood transposon. The transposon, in strains that had remained in abo homozygous conditions for several generations and had lost the abo maternal-effect, was no longer present in region 32E. Certain features of the abo mutation, discussed in the light of this finding, may be ascribed to the nature of the particular allele studied. PMID- 2574697 TI - Genetic analysis of an interspecific hybrid swarm of Populus: occurrence of unidirectional introgression. AB - Restriction fragment length polymorphisms were used to distinguish genotypes of two species of Populus, P. fremontii ('Fremont') and P. angustifolia ('narrowleaf'). Both inter- and intraspecific polymorphisms were detected in these cottonwood trees. The interspecific variation was much greater than the intraspecific variation. This permitted identification of parental genotypes within individual trees of a hybrid swarm which exists in an overlap zone between the two species. Within this hybrid swarm, individual trees are either F1 hybrids or backcrosses with a pure 'narrowleaf' parent; no progeny were found that could be attributed to crossing between F1 hybrid trees, or to backcrossing between F1 hybrid trees and 'Fremont'. PMID- 2574698 TI - Molecular and genetic characterization of Mu transposable elements in Zea mays: behavior in callus culture and regenerated plants. AB - Active Mutator lines of maize (Zea mays L.) have a high mutation rate and contain multiple hypomethylated 1.4-kb and 1.7-kb Mu transposable elements. Correlated with the inactivation of the Mutator system, these Mu elements cease to transpose and become more methylated. To determine whether the shock of tissue culture can affect Mutator activities, F1 progenies of outcrosses between active or inactive Mutator stocks and inbred line A188 were used to initiate embryogenic callus cultures. HinfI restriction digestion of genomic DNA isolated from 3-5-month-old cultures demonstrated that there is a very good correlation between the modification state of Mu elements in the cultures and the Mutator parent. Despite the dedifferentiation and rapid proliferation characteristic of tissue culture, the Mutator activity state is relatively stable during an extended tissue culture period. Cultures established from inactive Mutator lines were not reactivated; cultures established from active lines maintained a high Mu copy number, and most Mu elements remained unmodified. In contrast, weakly active Mutator parents gave rise to cultures in which Mu element modification could switch between low and high methylation during the culture period. Evidence for transposition was investigated with EcoRI digestion of genomic DNA isolated at different times during culture. The appearance of novel Mu-hybridizing fragments and a strong background hybridization are interpreted as evidence that transposition events occur during culture. Plants regenerated from such active cultures transmitted Mutator activity to their progeny. PMID- 2574699 TI - [Activity of enzymes in amniotic fluid in prenatal diagnosis of cystic fibrosis]. AB - The activity of microvillar enzymes--gamma-glutamyltranspeptidase, aminopeptidase, general and intestinal forms of alkalyne phosphotases was studied in amniotic fluid (AF) of 33 women with 25% risk of cystic fibrosis (CF) (mucoviscidoses) in their progeny. The figures obtained in this group were compared with corresponding values of the same enzymes in 100 AF samples from normal pregnancies (negative control) and with 9 AF samples from women which were known to give birth to the children with CF (positive control). CF has been predicted in 5 cases, pregnancies were artificially terminated in 4 women. Biochemical CF prediction was proved by immunochemical assay of albumin contents in meconium of fetal ileum. One woman from the high risk group refused abortion and gave birth to a CF child. Among 26 cases of low CF prediction, 13 resulted in birth of a child without a sign of CF, one - in a child with clear-cut diagnosis of CF and 12 other pregnancies still proceed. The efficiency of complex biochemical, pathomorphological and molecular approaches for verification of intrauterine CF diagnosis in aborted fetuses as well as for detection of heterozygous carriers of CF gene and prenatal diagnosis of CF is discussed. PMID- 2574701 TI - Treatment of duodenal ulceration: reflections, recollections, and reminiscences. PMID- 2574700 TI - Effect of sulphasalazine and its active metabolite, 5-amino-salicylic acid, on toxic oxygen metabolite production by neutrophils. AB - The possibility that the mode of action of sulphasalazine and its active metabolite 5-amino-salicylic acid (5ASA) involves modification of toxic oxygen metabolite production by neutrophils has been investigated by measuring the effect of these drugs on luminol-dependent chemiluminescence, superoxide release and oxygen consumption by stimulated neutrophils in vitro. 5ASA, and to a lesser extent sulphasalazine, had profound inhibitory effects on the luminol dependent chemiluminescent response of neutrophils stimulated with formyl-methionyl-leucyl phenylalanine (1 microM) + cytochalasin B (5 micrograms/ml). A concentration of 50 microM 5ASA or sulphasalazine produced 93.8 (2.3)% and 65.7 (3.7)% inhibition of control responses respectively. The concentration of 5ASA and sulphasalazine producing 50% inhibition of chemiluminescence were 3.6 (1.8) microM and 16.5 (6) microM respectively. Both drugs had little effect on the chemiluminescent response of neutrophils stimulated with phorbol myristate acetate (1 microgram/ml), producing only 11.4 (3.9)% and 34 (7)% inhibition respectively, at a concentration of 50 microM. Superoxide release from fMLP + CB stimulated neutrophils was also inhibited slightly by 5ASA (50 microM) by 35.6% and by sulphasalazine (50 microM) by 7.9%. Similarly, there was little inhibition in the rate of oxygen consumption by fMLP + CB stimulated neutrophils by either 5ASA or sulphasalazine at concentrations which produced near total abolition of luminol dependent chemiluminescence. These results show that sulphasalazine and 5ASA inhibit the reaction of toxic metabolites produced by stimulated neutrophils with luminol, without inhibition of the oxidase system producing these metabolites. The site of action of these drugs on neutrophils in vitro is thus extracellular, by scavenging a released metabolite, probably hypochlorite. This has important implications for their mode of action in vivo in inflammatory bowel disease. PMID- 2574702 TI - [Phenomenology and therapy of neuroleptic-induced akathisia--a review of the literature]. AB - The neuroleptic-induced akathisia (NIA) often appears as a side effect of neuroleptic therapy in psychotic individuals. It can accompany or outlive the period of neuroleptic treatment. Besides the objective symptoms of motor restlessness it is especially the subjective symptoms and complaints as inner restlessness, anxiety, and depression, which cause severe annoyance or even torment patients. Exacerbations of disease symptoms treated with neuroleptics can occur. After outlining development of the concept of akathisia and of the knowledge of NIA some relevant findings in the field of NIA, especially in respect to their clinical pictures and their connections to related neuroleptic induced side effects, are discussed. Development and present stand of treatment of NIA are described. Treatment with betablockers plays a central role. Pathophysiological aspects are touched in context with therapeutical considerations. The current state of knowledge of NIA allows a better understanding of pathophysiology in neuroleptic side effects in general, enables an almost sufficient treatment of NIA with betablockers, demonstrates the necessity of responsible and cautious use of neuroleptics by physicians and the necessity of careful guidance of such patients who are treated with neuroleptics. PMID- 2574703 TI - Immunogold distribution of actin during spermiogenesis in the normal rabbit and after experimental cryptorchidism. AB - Immunogold procedures for actin detection were used in combination with experimental cryptorchidism in the rabbit as a model to shed more light on the function of subacrosomal actin during spermiogenesis. In the normal testis, actin was localized in the perinuclear substance (PNS) from round spermatid onward but it was not detected in late spermatids. Actin labeling in each type of spermatid was essentially unmodified after 24 hr of cryptorchidism. However, among relevant immediate and delayed effects, discontinuous acrosomes overlying a continuous PNS with normal actin labeling were noted. Nuclear invaginations were seen in combination with subacrosomal dilatations; at this site actin labeling was found only in the PNS closely apposed to the nuclear envelope. In subacrosomal areas lacking PNS, actin labeling also was lacking. These results suggest that the subacrosomal actin (F-actin) is a component of the PNS that is tightly bound to the nuclear envelope rather than the overlying inner acrosomal membrane. Therefore, a function for the subacrosomal actin either in anchoring the acrosome to the nucleus or in capping the inner acrosomal membrane appears unlikely. The data rather suggest a capping function for the nuclear membrane during spermiogenesis. PMID- 2574704 TI - Adrenergic stimulation of sea urchin sperm cells. AB - The noradrenergic agonists norepinephrine and isoproterenol elicit greater stimulatory swimming responses in sea urchin spermatozoa than epinephrine. The beta-blocker atenolol induces an even greater motile rate, while the alpha blocker phentolamine has only a moderate effect, it also causes a minimal reduction in the sperm cells' response to atenolol. Caffeine increases the motility but to a lesser degree than 8-Br-cAMP. In drug interaction assays, both caffeine and 8-Br-cAMP depress the adrenergic effects. Agents that affect access of calcium to the flagellar apparatus (verapamil and trifluoperazine) depress the motility below the level of the controls when incubated separately with the sperm suspensions and counteract the stimulation due to atenolol. Adrenergic modulation of sperm motility thus appears to be both a calcium-dependent and a cyclic nucleotide-dependent process. PMID- 2574705 TI - An immunohistochemical study of the presence of c-erbB-2 protein in Paget's disease of the nipple. AB - Tumours from 45 patients with Paget's disease of the nipple have been stained with antibody 21N which was raised against a peptide from the C-terminus of the predicted c-erbB-2 protein. Positive staining was observed in 41 cases (91%). In 42 cases the underlying mammary carcinoma was also available for study. In all but two cases staining was similar in the Paget's cells and the underlying carcinoma whether the latter was purely in situ ductal (35%) or in situ associated with infiltrating carcinoma (65%); the malignant cells in both components were large and pleomorphic and the in situ ductal carcinoma was of the comedo type. In the two exceptions the underlying carcinoma showed different histological features. The significance of the high levels of c-erbB-2 protein in this pattern of mammary carcinoma is considered. PMID- 2574706 TI - An investigation of possible iatrogenic damage caused by metal rubber dam clamps. AB - Rubber dam may be held in place over a tooth by metal clamps. It has been shown that a mismatch of contact between the clamp gripping edge and the tooth surface may be reduced to a point contact, thereby concentrating the gripping force generated by the bow of the clamp. Experiments were conducted to measure the force. Clinically realistic loading of the tooth surface by sections of the gripping edge of clamps was carried out using special apparatus. Examination by scanning electron microscopy showed that iatrogenic damage to the tooth could occur. Therefore a plea is made for clamps to be redesigned to reduce any harm. PMID- 2574707 TI - Washed intrauterine insemination--indications and success. PMID- 2574708 TI - Exacerbation of adenomyosis symptomatology by estrogen-progestin therapy: a case report and histopathological observations. AB - The present case report illustrates the hormonal sensitivity of adenomyosis. Administration of an estrogen-progestin combination for what was felt to be symptomatic endometriosis resulted in exacerbation of symptoms and growth of adenomyomas. Histopathologic examination of the hysterectomy specimen revealed a pattern of decidualization previously unreported, but consistent with current theories of experimental in vivo and in vitro decidua formation. PMID- 2574710 TI - Semen quality in Norwegian men over a 20-year period. AB - Semen parameters of 135 randomly selected men in 1966 were compared with semen analysis of 148 men in 1986 to assess whether semen characteristics had changed during the period. Both groups of men were of barren couples; median age was identical in the two groups (31 years). The semen analyses included volume, sperm density, and sperm morphology. Significant change over the time period was observed only for the percentage of normal morphology. This parameter deteriorated from 60% in 1966 to 41% in 1986 (median values; p less than .001). This study, like studies from other industrialized countries, indicates a decline in semen quality over the past decades. PMID- 2574709 TI - The optimization of laparoscopic oocyte recovery. AB - Although there is an increasing trend to ultrasound-guided techniques of oocyte recovery, the laparoscopic method has had a traditional role which will continue to be applied in many circumstances. The optimization of oocyte recovery is dependent upon timing factors (inducing the surge at the appropriate stage of follicle maturation); the instrumentation (a dual-lumen needle which allows for continuous flushing is optimal); and improving the accessibility of the ovaries using preliminary pelvic adhesiolysis to create improved access. PMID- 2574711 TI - Clinical application of the swim-up and washing of human spermatozoa. AB - Artificial insemination with husband's semen is one of the treatments in cases of male infertility. A technique for swim-up and washing sperm is described. A special device was used for introduction of sperm into the uterus. Sperm density after treatment by swim-up and washing of sperm was lower than in the pretreatment specimens, but sperm motility, motile sperm count, and conception rate after treatment were higher. PMID- 2574712 TI - Serum concentrations of pituitary and testicular hormones in infertile Nigerian males. AB - Serum concentrations of luteinising hormone, follicle stimulating hormone, prolactin, and testosterone were measured by radioimmunoassay in 384 male partners of infertile Nigerian couples in order to assess the prevalence of abnormalities of these hormones in this population of African males. Eighty-eight (23%) of the patients had hyperprolactinemia, which was associated with subnormal testosterone concentration in 38 patients. Thirteen percent had features suggesting either primary gonadal failure or germinal tubular dysfunction, while 1% had hypogonadotropic hypogonadism. The results show that a substantial proportion of our infertile males have abnormalities of the hormones measured. It is suggested that the estimation of these hormones should be an integral part of the evaluation of infertile African males, since the information so provided will be of value in the management and treatment of a large number of these patients. PMID- 2574714 TI - The use of hyaluronic acid for sperm selection--evaluation of sperm head ultrastructure. AB - The percentage of normal spermatozoal plasma membranes and acrosomes was evaluated by electron microscopy before and after a two-step semen washing and swim-up into culture medium containing either bovine serum albumin or hyaluronic acid. Both techniques of sperm selection increased the concentration of motile spermatozoa when compared with the fresh ejaculate (P less than .001). The percentage of sperm with ultrastructurally intact plasma membranes and acrosomes was increased after both separation procedures in comparison with the original ejaculate (P less than .01). In addition, both techniques of sperm selection significantly reduced the content of sample debris, granulocytes, and nonviable spermatozoa (P less than .01). PMID- 2574713 TI - Persistence of human cytomegalovirus DNA sequences without cell-virus homology in human placental explants in culture. AB - Using histopathology, virology, and molecular probing, we investigated the potential of human first-trimester placental tissue to support human cytomegalovirus (HCMV) infection. Histopathologic examination of infected placental explants revealed cellular changes characteristic of HCMV infection. Immunohistochemical staining of infected explants with human convalescent sera demonstrated expression of HCMV antigens within the cytotrophoblast. Dot blot hybridization of DNA extracted from infected placental tissue using cloned Hind III "W" fragment of HCMV genome indicated the presence of HCMV sequences without virus-cell homology in infected explants from one to ten days post-infection. In general, the sequences detected by the viral probes increased in abundance with time as infection continued. PMID- 2574715 TI - Inhibitors of the enkephalin degrading enzymes. Modulation of activity of hydroxamate containing compounds by modifications of the C-terminal residue. AB - To further characterize the S'2 subsite of both the neutral endopeptidase (EC 3.4.24.11, NEP) and aminopeptidase N (EC 3.4.11.2, APN), two enzymes physiologically involved in enkephalin metabolism, a new series of hydroxamate inhibitors containing a cyclic amino acid as the P'2 component were synthesized. These amino acids differ by the size of the cycle, the relative position of the functional groups, and their absolute configuration. Highly efficient inhibitors of NEP were obtained whatever the modification on the P'2 component, while for APN inhibition, a cyclic beta-amino acid was preferred. The most active inhibitors contained a trans cyclopentyl beta-amino acid and a cis or a trans cyclohexyl beta-amino acid. When injected intracerebroventricularly in mice, these two latter compounds elicited potent antinociceptive responses on both the jump latency and the fore paw lick times. PMID- 2574716 TI - Schizophrenia, affective psychoses, and other disorders treated with neuroleptic drugs: the enigma of tardive dyskinesia, its neurobiological determinants, and the conflict of paradigms. PMID- 2574717 TI - Functional aspects of three molecules associated with metastasis development in human malignant melanoma. AB - To identify molecules which may be functionally associated with the development of metastasis in human melanoma, monoclonal antibodies which discriminate between benign and malignant melanocytic lesions in situ were selected. Biochemical studies and cDNA cloning identified the antigens HLA-DR, ICAM-1 and MUC18 which showed an expression pattern on primary tumors correlating with vertical tumor thickness, the most predictive parameter for the development of metastasis in melanoma. ICAM-1 and MUC18 show sequence similarity to a family of cell adhesion molecules which include the neural cell adhesion molecule NCAM. Both HLA-DR and ICAM-1 can be induced on melanoma cells by lymphokines, suggesting a role of the mononuclear cell infiltrate in the control of tumor cell phenotype. Knowledge of the normal function of these molecules allows one to hypothesize how they may contribute to the successful development of metastases. PMID- 2574718 TI - Respiratory effects of N-methyl-D-aspartate on the ventrolateral medullary surface. AB - We studied the central effects of N-methyl-D-aspartate (NMDA) on respiration in 18 artificially ventilated cats anesthetized with alpha-chloralose. Unilateral topical application of NMDA (1 x 10(-8) mol) to the intermediate region of the ventrolateral medulla exaggerates the phrenic response to CO2 at end-tidal PCO2 levels of less than 50.0 Torr. At higher end-tidal PCO2 levels, however, such differences disappear. Unilateral NMDA application increases the activity of the right and left phrenic nerves equally. Furthermore, the magnitude of the phrenic response after unilateral application of NMDA was not different from that after bilateral application. NMDA also had a vasopressor action when applied to the ventrolateral medullary surface. In contrast to respiratory responses, bilateral application of NMDA caused a significant increase in blood pressure compared with unilateral application of NMDA. Application of the NMDA antagonist 2-amino-5 phosphonovaleric acid abolished both the blood pressure and respiratory effects of NMDA. These results suggest that CO2 and NMDA may act on a common respiratory premotoneuron to produce stimulation of breathing. Because blood pressure responses, unlike respiratory responses, were greater after bilateral application than after unilateral application of NMDA, it is suggested that the neural substrates for the two effects of NMDA seem to be different. PMID- 2574719 TI - A comparison of two adjunctive treatment strategies in acute mania. AB - A benzodiazepine-neuroleptic adjunctive treatment strategy in a cohort of acutely manic patients was compared with standard neuroleptic adjunctive treatment in a matched sample treated in the same hospital. Thirty newly hospitalized manic patients receiving low-dose neuroleptic (310 mg/day chlorpromazine equivalents) and benzodiazepines (1.6 mg/day lorazepam equivalents) were compared, retrospectively, with 30 statistically similar patients receiving standard dose neuroleptic adjunctive treatment (590 mg/day chlorpromazine equivalents; 0.09 mg/day lorazepam equivalents). The benzodiazepine-neuroleptic-treated group demonstrated significantly fewer seclusion and restraint episodes (p less than .05) and were comparable on other parameters. Treatment with the benzodiazepine neuroleptic combination may lead to fewer inpatient complications than standard neuroleptic treatment alone. PMID- 2574720 TI - Recent developments in genetics of manic-depressive illness. AB - Bipolar affective disorder appears to be a heterogeneous disorder with multiple independently inherited disease genes, each giving similar clinical results (bipolar, unipolar, and other disorders). This conclusion derives from the recent findings of separate forms of illness linked to single gene markers, with the preponderance of cases in several studies not linked to any of them. At this time, reports of linkage to chromosome 11 and to the color-blindness region of X chromosome are widely accepted, but reports of linkage of the HLA region of chromosome 6 have been criticized and are considered controversial. Persons born in successive decades of the 20th century have progressively greater risks for bipolar and unipolar affective disorders, suicide, and alcoholism but not schizophrenia. This multinational trend begins with persons born in the 1930s and extends to the present time (or possibly until the present decade). For affective disorders, this trend has greater effect in families of affective disorder patients than in the population as a whole, implying a genetic-environment interaction. PMID- 2574721 TI - Hb Catonsville (glutamic acid inserted between Pro-37(C2)alpha and Thr 38(C3)alpha). Nonallelic gene conversion in the globin system? AB - Hb Catonsville is an unstable variant in which glutamic acid is inserted into the alpha-globin chain between Pro-37(C2) and Thr-38(C3). The peptide sequence data are consistent with the DNA sequence of the polymerase chain reaction-amplified fragment of the variant globin gene, which shows the insertion of the triplet codon--GAA--into the mutant alpha-globin gene. In the normal alpha-globin gene cluster the codon for glutamic acid is GAG rather than GAA. Thus, there are two features unique to Hb Catonsville, one the insertion of a single residue into the interior of the alpha-globin chain, and two the presence of the alternate codon for glutamic acid. The experimental evidence suggests that Hb Catonsville may be an example of nonhomologous nonallelic gene conversion, an observation not previously reported in this gene family. The mutation occurs in the critical alpha 1 beta 2 interface of the hemoglobin tetramer and leads to a variant with high oxygen affinity, a reduced cooperativity, and Bohr effect. PMID- 2574722 TI - Multiple domains of botulinum neurotoxin contribute to its inhibition of transmitter release in Aplysia neurons. AB - The binding, internalization, and inhibition of transmitter release by botulinum neurotoxin (BoNT) was investigated using the intact toxin, its heavy (HC) or light (LC) chains, and a proteolytic fragment thereof. In Aplysia neurons, blockade of acetylcholine release upon external application of BoNT types A or E was prevented by reducing the temperature to 10 degrees C, due to arresting intoxication at the membrane binding step. At this low temperature, type A HC, H2 (comprised of the N-terminal of HC), or H2L (H2 disulfide-linked to LC) antagonized the neuroparalytic action of BoNT A or E, indicating that the latter bind saturably to common ecto-acceptor via the H2 region. In contrast, H2L was unable to counteract BoNT-induced paralysis at the murine neuromuscular junction. In accordance with this species difference, unlike native BoNT, saturable binding of 125I-labeled H2L could not be detected in mammalian peripheral or central nerve terminals. Possibly, more stringent structural requirements form the basis of the toxin's greater effectiveness in inhibiting neurotransmission at mouse nerve muscle synapses than Aplysia nerve terminals. In further identification of functional domains in the toxin, an unprocessed single-chain form of BoNT type E was found to be ineffective when applied extra- or intracellularly to Aplysia neurons. Notably, bath application of the latter to a neuron preinjected with HC, but not H2L or LC, resulted in a blockade of release. This shows that the single chain species can become internalized and requires, not only LC, but also processed HC for its inhibitory action; consistently, the proteolyzed form of BoNT E was active. PMID- 2574723 TI - Expression of macrophage-lymphocyte Fc receptors in Madin-Darby canine kidney cells: polarity and transcytosis differ for isoforms with or without coated pit localization domains. AB - Many cells of the immune system and certain epithelia express receptors for the Fc domain of IgG (FcR). On mouse macrophages and lymphocytes, two distinct receptor isoforms have been identified, designated FcRII-B1 and FcRII-B2. The isoforms are identical except for an in-frame insertion of 47 amino acids in the cytoplasmic tail of FcRII-B1 that blocks its ability to be internalized by clathrin-coated pits. We have recently found that at least one IgG-transporting epithelium, namely placental syncytial trophoblasts, expresses transcripts encoding a receptor similar or identical to macrophage-lymphocyte FcRII. To determine whether FcRII of hematopoietic cells might also function as a transcytotic receptor if expressed in epithelial cells, FcRII-B1 and -B2 were transfected into Madin-Darby canine kidney (MDCK) cells and grown on permeable filter units. The two FcRII isoforms exhibited different patterns of polarized expression: FcRII-B1 was localized mainly to the apical plasma membrane domain, whereas FcRII-B2 was found predominantly on the basolateral surface. As expected for FcR in placenta, FcRII-B2 and to a lesser extent FcRII-B1 mediated transcellular transport of IgG-complexes from the apical to the basolateral plasma membrane. Neither receptor mediated transcytosis in the opposite direction, although FcRII-B2 also delivered ligand to lysosomes when internalized from either the basolateral or apical domains. Furthermore, FcRII-B2 was capable of transporting monovalent antireceptor antibody Fab fragments across the cell, suggesting that transcytosis was not dependent on receptor cross-linking. These findings suggest the possibility that FcRII can mediate transepithelial IgG transport when expressed in placental syncytial trophoblasts in addition to its "classical" endocytic and signaling activities when expressed in macrophages. Because FcRII-B1 and -B2 are expressed with distinct polarities, the results also suggest that interactions with clathrin-coated pits may play a role in generating the polarized distribution of at least some plasma membrane proteins in MDCK cells. PMID- 2574724 TI - Involvement of protein phosphatases 1 and 2A in the control of M phase-promoting factor activity in starfish. AB - Specific inhibition of types 1 and 2A protein phosphatases by microinjection of okadaic acid (OA) into starfish oocytes induced germinal vesicle breakdown and activation of M phase-promoting factor (MPF) and histone H1 kinase. The effects were evident in immature oocytes arrested at first meiotic prophase as well as in fully mature oocytes arrested at the pronucleus stage. In addition, MPF and histone H1 kinase were stabilized for several hours and protected from inactivation by inhibition of type 1 protein phosphatases with either OA or specific anti-phosphatase antibodies. Microinjection of okadaic acid was associated with unusual changes of the microtubule network, including the disappearance of spindles and extension of the cytoplasmic array of microtubules. MPF activation after OA injection was associated with dephosphorylation of phosphothreonine and phosphoserine residues in cdc2, showing that neither type 1 nor 2A protein phosphatases catalyzes these dephosphorylations. The effects of OA on MPF activation and inactivation appeared to involve the cyclin subunit. OA did not induce MPF activation in the absence of protein synthesis and it prevented degradation of cyclin. Therefore protein phosphatases types 1 and 2A appear to be involved in activation and inactivation of MPF involving mechanisms that operate after cyclin synthesis and before its degradation. PMID- 2574727 TI - Clinical pharmacology of dilevalol (III). A pharmacokinetic study of dilevalol in elderly subjects with essential hypertension. AB - Dilevalol (100 mg) was given once daily for 8 days in eight elderly subjects with essential hypertension. Blood samples for plasma dilevalol concentrations were taken during an 8-hour post-drug period following the first and eighth dosages, and the time to maximum concentration (tmax), maximum plasma concentration (Cmax), distribution half-life (t1/2 alpha), elimination half-life (t1/2 beta) and area under the plasma concentration-time curve (AUC) were determined. A wide intra-subject variability was observed in tmax during the repeated administration. A high inter-subject variability was also demonstrated in tmax, Cmax, t1/2 beta and AUC during both observation periods. No significant difference was observed, however, in these pharmacokinetic parameters between the first and eighth dosages. These data indicate that the pharmacokinetic profiles of dilevalol are not altered during 8 days of therapy in elderly subjects with essential hypertension. Since elderly subjects are potentially heterogenous in capacities for handling the drug, the observed variability in pharmacokinetic parameters may reflect the heterogeneity in the sample chosen for examination in the current study. PMID- 2574725 TI - Hepatocyte differentiation in vitro: initiation of tyrosine aminotransferase expression in cultured fetal rat hepatocytes. AB - A fetal rat hepatocyte culture system has been used to study the molecular mechanisms of tyrosine aminotransferase (TAT) gene expression during development. It has previously been shown that TAT activity can be detected in 19-d, but not 15-d, gestation hepatocytes on the first day of culture (Yeoh, G. C. T., F. A. Bennett, and I. T. Oliver. 1979. Biochem. J. 180:153-160). In this study enzyme activity, synthesis, and mRNA levels were determined in hepatocytes isolated from 13-, 15-, and 19-d gestation rats maintained in culture for 1, 2, or 3 d and exposed to dexamethasone. TAT expression is barely detectable in 13-d gestation hepatocytes even after 3 d in culture. Hepatocytes isolated from 15-d gestation fetuses have undetectable levels of enzyme activity and synthesis on the first day of culture; both can be assayed by days 2 and 3. TAT mRNA levels in these hepatocytes, measured by hybridization with a specific cDNA, increase substantially during culture. TAT activity, synthesis, and mRNA are evident on the first and subsequent days of culture in 19-d gestation hepatocytes. Transcription measurements in isolated nuclei indicate that the increase in TAT mRNA in 15- and 19-d gestation hepatocytes is associated with an increase in transcription of the gene. Immunocytochemical studies demonstrated that the increase in TAT expression correlated with an increase in the proportion of hepatocytes expressing the enzyme, rather than a simultaneous increase in all hepatocytes. These results support the proposal that a subpopulation of 15-d fetal hepatocytes undergo differentiation in culture with respect to TAT. PMID- 2574726 TI - Constitutive and stimulus-induced phosphorylation of CD11/CD18 leukocyte adhesion molecules. AB - The leukocyte CD11/CD18 adhesion molecules (beta 2 integrins) are a family of three heterodimeric glycoproteins each with a distinct alpha subunit (CD11a, b, or c) and a common beta subunit (CD18). CD11/CD18 mediate crucial leukocyte adhesion functions such as chemotaxis, phagocytosis, adhesion to endothelium, aggregation, and cell-mediated cytotoxicity. The enhanced cell adhesion observed upon activation of leukocytes is associated with increased surface membrane expression of CD11/CD18, as well as a qualitative upregulation of CD11/CD18 functions. To elucidate the nature of the qualitative modifications that occur, we examined the phosphorylation status of these molecules in resting human leukocytes and upon activation with PMA or with the chemotactic peptide F-met-leu phe (FMLP). In unstimulated cells, all three CD11 subunits were found to be constitutively phosphorylated. In contrast, phosphorylation of the common CD18 subunit was minimal. PMA induced rapid and sustained phosphorylation of CD18 that occurred at high stoichiometry, but had only minimal effects on phosphorylation of the associated CD11 subunits. FMLP also induced rapid phosphorylation of CD18, but the effect was of short duration. FMLP-induced phosphorylation of CD18 was not related to its Ca++-mobilizing effect, as CD18 phosphorylation was not observed upon treatment of leukocytes with the Ca++ ionophore, ionomycin. Phosphoamino acid analysis of CD11/CD18 in PMA- or FMLP-treated monocytes revealed a predominance of phosphoserine residues in all CD11/CD18 subunits. A small component of phosphothreonine was present in CD11c and CD18 and a minor component of phosphotyrosine was also detected in CD18 upon leukocyte activation may regulate the adhesion functions mediated by the CD11/CD18 family of molecules. PMID- 2574728 TI - The efficacy and tolerability of nifedipine (NIF) and nisoldipine (NIS) both alone and combined with a beta-blocker in patients with essential hypertension: a multicenter, parallel-group study. AB - We have assessed the efficacy and tolerance of Nifedipine twice daily and Nisoldipine once daily, both alone and in combination with a beta-blocker in 171 essential hypertensives in a randomized parallel comparison fashion. Both drugs were equally effective in lowering blood pressure: 72.6% of the subjects on Nisoldipine and 80.5% of those on Nifedipine reached a supine diastolic blood pressure less than or equal to 90 mmHg. Spontaneously reported side effects were frequent but no biochemical, hematological or electrocardiographic abnormalities were detected. PMID- 2574729 TI - The efficacy and safety of dilevalol in patients with chronic stable angina pectoris. AB - This is the first reported large clinical trial of the antianginal and acute ischemic effectiveness and safety of dilevalol (the R, R-isomer of labetalol) in patients with chronic stable angina pectoris. This was a multicenter double blind fixed-dose parallel group placebo controlled trial. Patients with chronic stable angina and positive and reproducible exercise tests (+/- 20%) were included. If randomized, patients entered one of four fixed dose groups (twice a day placebo, 100 mgm, 200 mgm and 400 mgm bid for 2 weeks). Exercise testing was performed at 2 hours (peak) and 12 hours (trough) postdosing. This was followed by a 2-week once-a-day dosing regimen in which patients received the same total daily dose as the prior 2 weeks, with the full dose in the morning and a matched placebo in the evening. Exercise testing was performed at 2 hours (peak) and 24 hours (trough) postdosing. Anginal frequency and NTG consumption were significantly reduced, and equally so, by qd and bid regimens. The time of exercise to the onset of angina increased and the proportion of patients terminating exercise because of moderate angina decreased in a dose response fashion for both peak and trough tests and for both qd and bid regimens. There was also a dose related decrease in exercise induced ST segment depression and an increase in time to 1 mm ST depression. In 15 patients, 24-hour ambulatory monitoring also revealed a decrease in episodes of silent ischemia. No significant side effects related to the study drug occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574730 TI - Pustular dermatosis of the scalp associated with autoimmune diseases. AB - A 36-year-old woman visited our hospital with a five month history of persistent pustulation, crusting, and alopecia on the vertex of the scalp. No pathological organisms were isolated from the lesions. Histological examination revealed non specific changes of chronic inflammation with destroyed follicles. Antibiotic therapy produced no response, but steroid therapy was effective. From these observations, a diagnosis of erosive pustular dermatosis of the scalp (EPDS), as described by Pye et al., was made. The patient also had Hashimoto's thyroiditis, autoimmune hepatitis, and Takayasu's aortitis. The laboratory studies revealed an increased erythrocyte sedimentation rate, C-reactive protein 3+, hypergammaglobulinemia, and various auto-antibodies, suggesting the possibility of a pathogenesis common to both this dermatosis and the autoimmune diseases. PMID- 2574731 TI - H1-receptor antagonists: clinical pharmacology and therapeutics. AB - Each H1-receptor antagonist has unique pharmacokinetic and pharmacodynamic properties, and each H1-antagonist has unique potency and potential for causing adverse effects. Some of the first-generation H1-receptor antagonists should no longer be used because their relative lack of efficacy is combined with a high potential for causing adverse effects. Some of the new H1-receptor antagonists, in manufacturers' recommended doses, seldom cause sedation but may have only modest potency. The choice of optimal H1-receptor antagonist treatment for each patient should be based on up-to-date clinical pharmacology information. PMID- 2574732 TI - Formoterol, a new long-acting selective beta 2-adrenergic receptor agonist: double-blind comparison with salbutamol and placebo in children with asthma. AB - We compared the protective effect and duration of action of inhaled formoterol, a new, long-acting, selective beta 2-agonist, to inhaled salbutamol and placebo in a double-blind, randomized, crossover study in 16 children with asthma with a mean age of 10.3 +/- 0.4 years. Mean baseline FEV1 was 96 +/- 3% predicted and mean provocative concentration of methacholine (milligrams per milliliter) required to decrease FEV1 by 20% (PC20) was 0.81 +/- 0.25 mg/ml of methacholine. On the 4 study days, baseline FEV1 was within 10% of the FEV1 on visit 1, and baseline PC20 was within one doubling dose of visit 1. Each day patients inhaled either placebo, salbutamol, 200 micrograms, formoterol, 12 micrograms, or formoterol, 24 micrograms. FEV1 and PC20 were measured repeatedly during 12 hours. After placebo inhalation, mean FEV1 did not change significantly during 12 hours. After salbutamol inhalation, the mean FEV1 was significantly increased for less than 3 hours, but after formoterol inhalation, 12 or 24 micrograms, the mean FEV1 was significantly increased for 12 hours. After placebo treatment, mean PC20 did not change significantly. After salbutamol inhalation, mean PC20 was significantly increased for only 3 hours, but after formoterol inhalation, 12 or 24 micrograms, mean PC20 was significantly increased for 12 hours. Protection by formoterol, 12 and 24 micrograms at 12 hours, was equivalent to protection by salbutamol at 3 hours. Inhaled formoterol is a potent, long-acting bronchodilator and provides significantly better antiasthma protection than inhaled salbutamol. PMID- 2574733 TI - Theophylline, beta-adrenergic agents, and calcium channel blockers. PMID- 2574734 TI - [Isolated necrotizing angiitis of the cervix uteri. Apropos of a case]. AB - A necrotizing arteritis isolated to the uterine cervix without multisystem disease was fortuitously discovered in a 52-year old woman after hysterectomy for uterine leiomyomas. This rare lesion discovered by routine histopathological examination was cured by surgery. The aetiology and pathogenesis of this arteritis are unknown. PMID- 2574735 TI - Restriction fragment length polymorphisms of Anisakinae larvae. AB - The analysis of restriction fragment length polymorphisms (RFLPs) was applied to distinguish several kinds of Anisakinae larvae, Anisakis larvae (type I) collected from two different paratenic hosts, Anisakis larvae (type II) and Contracaecum larvae. The patterns of the two different paratenic host-derived DNA of Anisakis larva (I) were exactly the same in hybridized fragments generated by six endonucleases. The quite different patterns in RFLPs of genomic DNA were observed among the Anisakis larva (I), Anisakis larva (II) and Contracaecum larvae. The results suggest that the RFLPs analysis may be useful for distinguishing Anisakinae larvae and clarifying the relationships between Anisakis larvae and their adult worms. PMID- 2574736 TI - Effects of beta-endorphin, met-enkephalin, and dynorphin A on basal and stimulated insulin secretion in the mouse. AB - Since opioid peptides and opiate receptors have been demonstrated in the pancreatic islets, we investigated the effects of beta-endorphin, met-enkephalin, and dynorphin A, on basal and stimulated insulin secretion in the mouse. Each of the three opioid peptides was injected intravenously (0.06-64 nmol/kg) alone or together with each of the three insulin releasing agents glucose (2.8 mmol/kg), carbachol (cholinergic agonist, 0.16 mumol/kg), or terbutaline (beta 2 adrenoceptor agonist, 3.6 mumol/kg). It was found that beta-endorphin, met enkephalin, and dynorphin A were all without effect on basal plasma insulin levels, except a slight elevation by beta-endorphin induced at 2 min after its injection at 64 nmol/kg (to 41 +/- 2 microU/mL vs 28 +/- 4 microU/mL in controls; p less than 0.05). Glucose- and terbutaline-induced insulin secretion were inhibited by beta-endorphin at the lower dose levels of 0.25 (p less than 0.01) and 1 nmol/kg (p less than 0.05). This effect was counteracted by the opiate receptor antagonist naloxone (500 micrograms/kg). In contrast, beta-endorphin at the high dose levels of 16 and 64 nmol/kg augmented the glucose- and terbutaline induced insulin secretion (p less than 0.05). Carbachol-induced insulin secretion was not affected by beta-endorphin at the lower dose levels but augmented by the peptide at 64 nmol/kg (p less than 0.01). Met-enkephalin inhibited glucose- (p less than 0.01) and terbutaline- (p less than 0.05) induced insulin secretion at the high dose rates of 16 and 64 nmol/kg, but the peptide was without effect on carbachol-induced insulin secretion. The inhibitory effects were counteracted by naloxone. Dynorphin A did not affect stimulated insulin secretion at any of the dose levels tested. In summary, in the mouse 1. beta-Endorphin at low dose levels inhibits and at high dose levels augments stimulated insulin secretion; 2. Met enkephalin inhibits stimulated insulin secretion; and 3. Dynorphin A does not affect insulin secretion. It is suggested that the main influence of beta endorphin and met-enkephalin under in vivo conditions in the mouse is to inhibit stimulated insulin secretion. PMID- 2574737 TI - Ammonia assimilation by Aspergillus nidulans: [15N]ammonia study. AB - 15N kinetic labelling studies were done on liquid cultures of wild-type Aspergillus nidulans. The labelling pattern of major amino acids under 'steady state' conditions suggests that glutamate and glutamine-amide are the early products of ammonia assimilation in A. nidulans. In the presence of phosphinothricin, an inhibitor or glutamine synthetase, 15N labelling of glutamate, alanine and aspartate was maintained whereas the labelling of glutamine was low. This pattern of labelling is consistent with ammonia assimilation into glutamate via the glutamate dehydrogenase pathway. In the presence of azaserine, an inhibitor of glutamate synthase, glutamate was initially more highly labelled than any other amino acid, whereas its concentration declined. Isotope also accumulated in glutamine. Observations with these two inhibitors suggest that ammonia assimilation can occur concurrently via the glutamine synthetase/glutamate synthase and the glutamate dehydrogenase pathways in low-ammonia-grown A. nidulans. From a simple model it was estimated that about half of the glutamate was synthesized via the glutamate dehydrogenase pathway; the other half was formed from glutamine via the glutamate synthase pathway. The transfer coefficients of nine other amino acids were also determined. PMID- 2574738 TI - Intracerebroventricular physostigmine-induced analgesia: enhancement by naloxone, beta-funaltrexamine and nor-binaltorphimine and antagonism by dynorphin A (1-17). AB - The antinociceptive action (tail-flick test) of physostigmine given i.c.v. to mice was enhanced by the administration intrathecally (i.t.) of narcotic antagonists. Doses, i.t., as low as 0.1 fentog of naloxone, 0.25 ng of beta funaltrexamine and 0.1 ng of nor-binaltorphimine enhanced physostigmine, 2 micrograms i.c.v., analgesia. These doses of opioid antagonists did not inhibit spinal mu receptors or kappa receptor agonist-induced analgesia as assessed by absence of effect on Tyr-D-Ala2-N-MePhe4-Gly-ol5 or U50,488H i.t. analgesia. Enhancing effects of the opioid antagonists were interpreted to indicate that i.c.v. physostigmine-induced analgesia was mediated spinally by an endogenous opioid which had an antagonistic effect. This putative opioid antagonist was postulated to be dynorphin A (1-17). Thus, i.t. administration of small doses of less than 10 pg of dynorphin was shown to antagonize the analgesic action of physostigmine, i.c.v. Furthermore, this effect of dynorphin was attenuated by the doses of naloxone, beta-funaltrexamine or nor-binaltorphimine which were effective in enhancing physostigmine-induced analgesia. We concluded that physostigmine given i.c.v. had two actions, the first produced analgesia and the second activated a system which had an antianalgesic effect. Evidence indicated that the latter effect was mediated by dynorphin A (1-17). This concept of dynorphin action may be the basis for some of the unusual findings of the analgesic action of naloxone in other situations and support the concept for a descending dynorphin A (1-17)-mediated antianalgesic system. PMID- 2574739 TI - Selective inhibition of excitatory amino acids by divalent cations. A novel means for distinguishing N-methyl-D-aspartic acid-, kainate- and quisqualate-mediated actions in the mouse spinal cord. AB - Biting and scratching behaviors produced by intrathecal injection of excitatory amino acid (EAA) agonists were examined to determine whether the biting and scratching behavioral effects produced by these compounds are altered selectively in vivo by coadministration with divalent cations. N-methyl-D-aspartate (NMDA) induced behavior was inhibited by both magnesium and calcium but not by zinc. Kainic acid (KA)-induced behavioral activity was also inhibited by coadministration with calcium but not by magnesium or zinc. In contrast to both NMDA and KA, calcium, magnesium and zinc failed to alter the intensity of quisqualic acid (Quis)-induced biting and scratching behaviors. Based on this selective inhibition of the three EAA subtypes by divalent cations, we examined the behavioral responses produced by Glu and Asp in combination with calcium or magnesium to identify the receptor population involved in these motor effects. Calcium antagonized the biting and scratching behavior produced by i.t. injected Glu in contrast with Asp which was inhibited significantly by magnesium. Our results support the concept that Glu and Asp produce biting and scratching behaviors by an interaction with distinct receptor populations in the spinal cord. To date, there are no selective antagonists at the KA or Quis receptors. Thus, a systematic examination of the selective inhibition of EAA activity by divalent cations in addition to currently available pharmacologic antagonists may prove to be a useful approach to the identification of NMDA, KA and Quis receptor interactions. PMID- 2574740 TI - Aspartate-releasing nerve terminals in rat striatum possess D-2 dopamine receptors mediating inhibition of release. AB - The release of endogenous aspartic acid has been investigated using synaptosomes from rat corpus striatum. Exposure in superfusion to a depolarizing concentration of KCl (15 mM) evoked an overflow of aspartate which was almost entirely calcium dependent. When added to the superfusion medium, dopamine (DA) and the selective DA D-2 receptor agonists quinpirole (LY-171555) and pergolide inhibited the K+ evoked aspartate release in a concentration-dependent manner. The natural agonist DA was very potent (IC50 = 1 nM). The selective D-1 receptor agonist SK&F 38393 had no effect on the release of aspartate. The selective D-2 receptor antagonist S-sulpiride, but not the R-enantiomer, antagonized the DA-induced inhibition of aspartate release. The DA effect was unaltered by SCH 23390, a selective dopamine D-1 receptor antagonist. The findings that 1) the release of endogenous aspartate evoked by depolarization was calcium-dependent and 2) the release of aspartate was potently modulated through D-2 receptors are compatible with the idea that aspartate is released as a transmitter from striatal axon terminals. The possibility that aspartate and glutamate are coreleased from these terminals is discussed. PMID- 2574741 TI - Differential antagonism of alpha-1 and alpha-2 adrenoceptor-mediated vasoconstrictor responses by a vasodilator peptide, urotensin I: comparison with nifedipine. AB - We showed previously that in the dog, but not in the rat, Urotensin I, (UI), a neuropeptide with corticotropin releasing factor activity, selectively dilated the mesenteric circulation. Even in the rat, mesenteric arteries tested in vitro exhibited greater vasodilator responsiveness to UI than arterial preparations from elsewhere. In the rat in vivo, UI caused a preferential inhibition of alpha 1 adrenoceptor-mediated vasoconstriction, but it was unclear whether this provided an explanation for selective vasodilatation. The present study was done in the rat 1) to determine whether the effect of UI on alpha-1 adrenoceptors differed in regional vascular beds and 2) to compare the inhibitory action of UI on these responses with that of the calcium antagonist, nifedipine. The inhibitory actions of UI were similar, qualitatively and quantitatively, in both the blood-perfused mesenteric circulation and hindquarters of the urethane anesthetized rat. In both systems, UI produced a greater inhibition of pressor responses to a selective alpha-1 adrenoceptor agonist, phenylephrine, than to norepinephrine or a selective alpha-2 adrenoceptor agonist, alpha methylnorepinephrine. Pretreatment with prazosin, a selective alpha-1 adrenoceptor antagonist, reduced the antagonistic action of UI on norepinephrine responses in both vascular beds in vivo and in the rat mesenteric artery in vitro. In contrast, prazosin potentiated the inhibitory actions of nifedipine on pressor responses to norepinephrine in vivo without having significant effects on the antagonistic actions of nifedipine on norepinephrine responses in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574742 TI - Lipolytic action of a new alpha-2 adrenergic antagonist of the piperazinopyrimidine family: RP 55462. AB - Recent investigations have demonstrated the in vitro lipid mobilizing effects induced by alpha-2 adrenergic antagonist administration and have focused attention on the putative therapeutic interest of such compounds in the treatment of obesity as adjuvants in caloric restriction programs. We studied the impact of RP 55462 [6-chloro-4-(isopropylamino)-5-(methyl)-2, piperazinopyrimidine], a new alpha-2 adrenergic antagonist compound of the piperazinopyrimidine family, on fat cell function. The alpha-2-blocking properties of this agent, which had been defined initially on the brain were confirmed on adipocytes. RP 55462 competed with [3H]yohimbine binding sites on human fat cell membranes and inhibited the antilipolytic action of alpha-2-agonist compounds (UK 14304, clonidine and epinephrine) in human and hamster fat cells. It was also noticed that RP 55462 alone was able to activate lipolysis in isolated fat cells from various species (man, rat, hamster and dog). Moreover, the lipolytic response induced by isoproterenol or synacthene was largely amplified in the presence of RP 55462 in rat fat cells which are the least alpha-2 adrenergic responsive tested. RP-55462 dependent stimulation of lipolysis was not affected by the presence of other alpha-2 adrenergic antagonists (idazoxan, yohimbine or phentolamine). Intravenous administration of RP 55462 in alert dogs promoted an increment in plasma nonesterified acid concentrations reflecting its lipid mobilizing action. In summary this study focuses attention on a new alpha-2-antagonist compound which exhibits an in vivo lipid mobilizing action which could be attributable to its alpha-2 adrenergic antagonist properties. Inasmuch as the lipolytic activity of RP 55462, revealed in in vitro studies, seems to be independent from its alpha-2 adrenolytic properties; further studies are required to define the mechanism of such a lipolytic effect as well as its possible involvement in in vivo conditions. PMID- 2574743 TI - Evidence from functional and autoradiographic studies for the presence of tubular dopamine-1 receptors and their involvement in the renal effects of fenoldopam. AB - Evidence from receptor-ligand binding and biochemical studies seems to suggest the possible existence of tubular dopamine DA-1 receptors in the rat kidney. However, it is not yet clear whether these putative tubular DA-1 receptors are involved in the functional renal responses elicited during the administration of DA and DA receptor agonists. In the present study we have examined the renal effects of several doses of selective DA-1 receptor agonist fenoldopam in pentobarbital-anesthetized rats in an attempt to unmask a direct tubular DA-1 receptor-mediated diuresis and natriuresis. Additionally, we have performed receptor-ligand binding and autoradiographic studies to examine the presence and localization of DA-1 receptors in various regions of the rat kidney. At the highest dose studied (2 micrograms/kg/min), fenoldopam produced diuresis and natriuresis, which was accompanied by a significant decrease in blood pressure and also a significant increase in glomerular filtration rate. At 1 micrograms/kg/min, the diuretic and natriuretic effects of fenoldopam were observed in the absence of any changes in blood pressure and glomerular filtration rate, but there was a significant increase in renal blood flow. However, at 0.5 micrograms/kg/min, fenoldopam-induced natriuresis and diuresis was not accompanied by any changes in blood pressure, renal blood flow or glomerular filtration rate, implying a direct tubular effect. These effects of fenoldopam appear to be mediated via activation of DA-1 receptors, because they were antagonized by the selective DA-1 antagonist SCH 23390.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574744 TI - DTG and (+)-3-PPP inhibit a ligand-activated hyperpolarization in mammalian neurons. AB - The effects of three compounds with high affinity for the haloperidol-sensitive alpha-binding site were studied with intracellular recordings in the vitro neuronal preparations of the rat locus ceruleus, rat dorsal raphe and the guinea pig submucous plexus. Both (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)-3 PPP] and 1,3-di-o-tolylguanidine (DTG) inhibited the hyperpolarization induced by a ligand-activated potassium conductance. In the locus ceruleus, (+)-3-PPP and DTG produced a maximal 40 to 45% inhibition of the [Met5]enkephalin hyperpolarization, and had EC50 values of 6.6 and 2.2 microM, respectively. In the submucous plexus, the two compounds had a similar action on the alpha-2 adrenoceptor agonist UK14304 hyperpolarization, producing a maximal 50% inhibition with EC50 values of 140 and 32 nM, respectively. In addition, DTG inhibited the alpha-2-mediated inhibitory postsynaptic potential in both preparations. In contrast, (+)-3-PPP increased and prolonged the inhibitory postsynaptic potential. This action is qualitatively similar to the actions of cocaine on locus ceruleus and submucous plexus neurons. Haloperidol (1-10 microM) shared none of these actions. It is concluded that DTG and (+)-3-PPP are inhibitors of the opiate and alpha-2-mediated hyperpolarization at a postreceptor site, possibly the potassium channel. In addition, (+)-3-PPP, but not DTG, inhibits norepinephrine reuptake. None of these effects appear to be related to the sigma -binding site, because haloperidol acted as neither an agonist nor an antagonist. PMID- 2574745 TI - Effect of an alkylating analog of prazosin on alpha-1 adrenoceptor subtypes and arterial blood pressure. AB - Previous studies have shown that a chemically reactive analog of prazosin, SZL 49, reduces the alpha-1 adrenoceptor population by a maximum of 60% (Kusiak et al., 1989). These data support the idea that alpha-1 receptor subtypes exist and only one is sensitive to alkylation by SZL-49. In the present study male rats were injected (i.p.) with SZL-49 (0.5-30 mg/kg) and the effects on [3H]prazosin binding, systemic arterial blood pressure and the pressor response to phenylephrine were assessed 24 hr later. SZL-49 treatment decreased the number of [3H]prazosin sites without affecting receptor affinity. The maximal reduction in binding sites was 60% (32 fmol/mg). At doses of 0.5-, 1-, 5- and 10-mg/kg SZL-49 reduced the receptor number to the same level (83 fmol/mg control; 47-60 fmol/mg treated). Injection of SZL-49 had no effect on resting blood pressure. However, drug treatment (0.5 mg/kg and greater) shifted the phenylephrine dose-response curve to the right. The maximal 1-, 5- and 10-mg/kg SZL-49, the ED50 for phenylephrine was approximately the same. Therefore, over a 20-fold range of SZL 49 concentrations no further reduction in receptor number or phenylephrine ED50 was observed. These data support the idea that S2L-49-sensitive and resistant alpha-1 receptors exist in vivo. The alkylation resistant receptor is capable of maintaining resting blood pressure. Furthermore, both receptors appear to be involved in mediating the increase in blood pressure observed with phenylephrine. PMID- 2574746 TI - Effect of clonidine on myocardial cyclic GMP content in the mouse-activation of central and peripheral alpha adrenoceptors. AB - Clonidine (0.23-3.77 mumol/kg i.p.) produced a dose-dependent increase in mouse myocardial cyclic GMP (cGMP) content. This effect was antagonized by yohimbine (0.03-1 mg/kg i.p.), but not by prazosin (1 mg/kg i.p.). The inhibition by yohimbine was biphasic. The cGMP response to clonidine was inhibited by atropine (5 mg/kg i.p.) and methylatropine (0.2-5 mg/kg i.p.). In mice pretreated with the ganglionic blocker hexamethonium, the cGMP response to clonidine persisted. St-91 [(2,6-diethylphenylamino)-2-imidazoline] (0.39-3.94 mumol/kg i.p.), a cogener of clonidine which does not cross the blood-brain barrier, also increased myocardial cGMP content. The potency of clonidine was similar in mice pretreated and nonpretreated with hexamethonium. Methylatropine did not affect the cGMP response to St-91 and to clonidine in ganglionectomized mice and yohimbine was a less potent antagonist. These results indicate that systemic administration of clonidine produces an increase in myocardial cGMP content by both a central and a peripheral action. The increase in cGMP can be due to a direct activation of cardiac prejunctional alpha-2 adrenoceptors and to stimulation of cardiac muscarinic receptors, a response secondary to an action of clonidine on central alpha-2 adrenoceptors. PMID- 2574747 TI - New signposts on the road to understanding psoriatic arthritis. PMID- 2574748 TI - The haemagglutinins and fimbriae of Proteus penneri. AB - The haemagglutinins and fimbriae produced by 18 strains of Proteus penneri were studied and compared with those formed by representative strains of other species of Proteeae. After repeated subcultures at 30 degrees C, 12 P. penneri strains formed only MR/K haemagglutinins which were associated with thin, non-channelled, type-3 fimbriae. Two strains formed simultaneously both MS and MR/K haemagglutinins associated with thick, channelled, type-1 fimbriae and type-3 fimbriae, respectively. Four strains formed simultaneously both MR/K and MR/P haemagglutinins. No P. penneri strain formed either MS or MR/P haemagglutinins alone under these conditions. The type-3 fimbriae from P. penneri strain E180 were isolated, purified and found to be protein of 19 Kda. Immunoelectronmicroscopy studies with antibody to the type-3 fimbriae of strain E180 showed that P. penneri strains at least two antigenic types of type-3 fimbriae. The type-3 fimbrial antigen of the vaccine strain E180 was shared by another eight strains of P. penneri. A further eight P. penneri strains and the strains representative of other genera within Proteeae had type-3 fimbriae of a different antigenic type. The formation of these haemagglutinins and fimbriae suggests that this organism is well endowed to be a urinary-tract pathogen. PMID- 2574750 TI - Reduction of glutamine synthetase specific activity in cultured astroglia by ferrous chloride. AB - Immature and mature rat astroglia in culture were assayed for glutamine synthetase (GS) activity after a single exposure to the epileptogen FeCl2. Cells were cultured with both standard and elevated extracellular potassium or glutamate (Glu) concentrations. FeCl2 reduced GS activity below control levels, whereas high Glu increased GS activity. However, stimulation by high Glu was significantly attenuated in cultures given both FeCl2 and high Glu, indicating that cells treated with FeCl2 were not able to respond as effectively to increased extracellular glutamate by increasing their GS activity. The significance of these findings is that glial regulation of the neuronal environment may be impaired, based on the proposed importance of GS in ammonia detoxification in the brain. PMID- 2574749 TI - Adherence of Pseudomonas aeruginosa to respiratory epithelium and the effect of leucocyte elastase. AB - The tracheobronchial secretions from patients with cystic fibrosis often contain high amounts of free proteases. To evaluate whether human leucocyte elastase (HLE) can favour the persistence of bacterial airways infection, we exposed the frog palate mucosa to HLE and then to radiolabelled Pseudomonas aeruginosa and followed the sequence of events by scanning electronmicroscopy. In response to HLE there was a marked outpouring of mucus and a desquamation of the epithelium. P. aeruginosa was shown to adhere to recently secreted granules of mucus and to the exposed submucosal underlying connective tissues. For the eight different bacterial strains studied, a significative adherence to HLE-injured mucosa was observed only in strains that possessed internal haemagglutinating activity. Neither the presence of fimbriae, nor of the mucoid exopolysaccharide, nor of the bacterial surface haemagglutinating activity could be related to adherence of P. aeruginosa to the injured mucosa. These results support the hypothesis that HLE enhances bacterial infection of the respiratory mucosa both by inducing mucus hypersecretion and by exposing receptors to the microbial adhesins. It is also suggested that P. aeruginosa internal lectins may be implicated in adherence to host tissues. PMID- 2574751 TI - Protection of acute ischemic myocardial injury by pharmacological intervention. AB - Pharmacological protection of acute ischemic myocardial injury was studied using diltiazem, bunazosin, coenzyme-Q10 (Co-Q), and nicorandil, in dogs of which the left anterior descending coronary artery was ligated for 60 min. Drugs were given intravenously prior to and/or during coronary ligation. Co-Q, bunazosin and diltiazem suppressed degradation of sarcoplasmic reticulum (SR) expressed as inhibitions of reduction in Ca++-dependent ATPase activity and degradation of major ATPase protein. Fine structures of ischemic myocardial cells were simultaneously retained as well. On the contrary, the effects of nicorandil on ischemic myocardial injury were few. It is likely that protection of ischemic myocardial injury could be expected with drugs which react with ischemic myocardium directly and inhibit excess inflow of extracellular Ca++ in ischemic myocardium. PMID- 2574752 TI - [Gene analysis of polyposis and colonic carcinoma]. PMID- 2574753 TI - [Breast cancer and oncogenes]. PMID- 2574754 TI - [Drug resistance and implication for therapy]. AB - One of the major problems in cancer chemotherapy is the development of drug resistance during treatment. The nature of drug resistance in cancer patients is complex. Recently, it has been found that tumor cells can acquire resistance to anticancer drugs. It is now generally accepted that drug resistance at the cellular level (cellular resistance) is also an important mechanism of drug resistance in patients. The elucidation of the resistance mechanisms has progressed well recently owing to the application of cellular and molecular techniques in addition to the usual biological and biochemical techniques. In this article, I describe the mechanisms of cellular resistance, especially those of multidrug resistance at the molecular level, and I also discuss possible approaches to overcoming drug resistance. PMID- 2574755 TI - [Various factors related to carbohydrate metabolism. Gastro-entero-pancreatic hormones]. PMID- 2574756 TI - [Diagnostic procedure and treatment of diabetic nephropathy]. PMID- 2574757 TI - [Impression on the First Congress of the Society of Health and Welfare]. PMID- 2574758 TI - [An electromyographic study of detrusor sphincter dyssynergia in neurogenic vesical dysfunction. Part 2. Changes after radical transurethral resection of prostate and response to alpha-adrenergic stimulation]. AB - The relevance of the type of detrusor sphincter dyssynergia (DSD) and motor unit analysis as examined by simultaneous recordings of electromyography (EMG) of the external urethral sphincter (EUS) and bladder pressure was discussed in the first report. In this report, they were analysed similarly before and after radical transurethral resection of the prostate (TUR-P) to see how it was effective in relieving DSD. Furthermore, the response of the EUS to alpha-adrenergic stimulation was examined by analyzing its motor unit activity. Radical TUR-P was performed in 18 cases. After radical TUR-P, there was an improvement in the type of DSD (3 cases) or in its sub-types (8 cases), associated with decrease in residual urine rate in 16 cases. EUS responded to alpha-adrenergic stimulation with an increase in the frequency of pre-existing motor units and recruitment of new motor units. After radical TUR-P,EUS was similarly activated when stimulated with alpha-adrenergics. These data indicated that radical TUR-P was effective in relieving DSD by suppressing or abolishing abnormal continence reflex. Moreover, alpha-adrenergic activation of EUS also seemed to suggest a possible sympathetic role in the genesis of DSD, although exact mode of its involvement in the somatomotor innervation of the EUS remains to be settled. PMID- 2574759 TI - Restriction fragment length polymorphism as a genetic marker of the c-myc oncogene in rats. PMID- 2574760 TI - [Current diagnosis and therapy of undescended testis]. AB - Although the etiology of maldescended testes is multifactorial, dysfunction of hypothalamic-pituitary-gonadal axis should be considered as the most important factor. The hormonal treatment with Gn-RH on its own or followed by hCG can provoke testicular descent and should be applied at 10th month of life. Failure, partial or transient success needs orchidopexy within the first two years of life to prevent infertility. If a concomitant hernia or a true ectopia is encountered, if patients are seen at an adolescent age and if the testes are truly cryptorchid, surgery is the treatment of choice. PMID- 2574761 TI - Hypertension and left ventricular diastolic function. AB - In recent years, there has been increased recognition of the relative importance of abnormalities of diastolic function in patients with essential hypertension. Indeed, diastolic dysfunction may be the earliest indicator of hypertensive heart disease. In this article, the mechanisms governing normal ventricular relaxation and the factors that may cause diastolic dysfunction are reviewed. Noninvasive clinical methods, particularly Doppler echocardiography and radionuclide angiography, for determination of diastolic function are outlined, and the limited experience in the management of hypertensive patients with abnormalities of diastolic function is discussed. When congestive heart failure develops in a patient with hypertension, it is especially important to determine whether it is due primarily to systolic or to diastolic left ventricular dysfunction. PMID- 2574763 TI - [The effect of neuroleptics given to the mentally retarded is not sufficiently proved]. PMID- 2574762 TI - Beta-adrenergic control and inter-relationships between heart rate and blood pressure in neonatal lambs. AB - Our aim was to develop a signal analysis method for revealing interrelationships between heart rate and blood pressure and for displaying the influence of autonomic nervous control on these signals in a chronic lamb model. A chronically instrumented neonatal lamb model was made to record ECG and direct arterial blood pressure (N = 15). Continuous two-minute recordings of blood pressure (BP) and ECG were digitised. The instantaneous heart rate signal (IHR) was derived from the ECG. The IHR and BP signals were bandpass filtered. Autospectra, cross spectra, coherence spectra and phase spectra for the signals were computed to study the relative magnitudes and inter-relationships of the cardiovascular signals under normal conditions and during beta-adrenergic blockade. It was noted that both in the BP and IHR there were oscillations at the frequency of less than 0.1 Hz and also at the respiratory rate around 0.6 Hz. Beta-blockade reduced the oscillations of the IHR in less than 30-day-old lambs. It did not affect the coherence spectra or the phase lag between the signals. During quiet sleep the variability of blood pressure was decreased. In over-30-day-old-lambs the beta blockade did not affect the variabilities of the cardiovascular parameters. These findings indicate that in neonatal lambs the sympathetic control system is a major regulator of cardiovascular interactions. PMID- 2574764 TI - Prevention of postmenopausal bone loss by tiludronate. AB - 76 healthy women, who had been menopausal for less than 96 months and who had never received any form of treatment to prevent bone loss, were entered into a randomised double-blind study. For the first 6 months, half the patients received tiludronate 100 mg daily, while the others received placebo. During the second 6 months, all patients received placebo. Bone mineral density of the lumbar spine decreased significantly by 2.1% (SE 0.8%) in the placebo group and did not significantly change in the tiludronate group (+1.33 [0.8]%). The difference in response between the groups was significant, as were the differences between values for corrected urinary hydroxyproline and calcium. Treatment with tiludronate was not followed by increased secretion of parathyroid hormone. A 6 month course of oral tiludronate may counteract postmenopausal bone loss for at least a year by decreasing bone resorption. PMID- 2574765 TI - Peripheral laser angioplasty with pulsed dye laser and ball-tipped optical fibres. AB - Laser angioplasty with the pulsed dye laser and integral ball-tipped optical fibres was used for primary treatment of occlusive femoropopliteal vascular disease in 26 limbs of 24 patients, all of whom warranted operative intervention. 19 had "critical ischaemia", 8 had pedal ulceration, and 4 had distal gangrene. The delivery device consisted of the laser fibre loaded retrogradely into a standard 6 mm balloon angioplasty catheter, and was introduced through a common femoral artery cutdown in an attempt to recanalise femoropopliteal occlusions of a mean length of 21 cm (range 3-49). Angiographic recanalisation was achieved with a mean energy of 250 J (range 38-727 J) in 23 of the 26 limbs; in each case the channel created by the laser fibre was augmented by balloon angioplasty. Technical failure occurred in 3 patients, due to wall dissection, persistent side branch entry, and incomplete lesion penetration, respectively. Acute occlusion within 48 h occurred in 2 diabetic patients with very poor run-off and distal gangrene, and early failure occurred in another patient due to inadequate balloon dilatation. 1 patient with segmental tibial disease below a technically successful recanalisation did not show clinical improvement. Several patients had coexisting coronary artery disease, 3 of whom died of myocardial infarction--all with patent femoropopliteal vessels. In the 21 survivors, 14 vessels remained patent at a median of 7 months' follow-up. PMID- 2574766 TI - Oxpentifylline in endotoxaemia. AB - Oxpentifylline (pentoxifylline), which is known to have pharmacological effects in animal models of respiratory distress syndrome, multiorgan failure, and shock, was tested in human beings after injection of endotoxin. Of ten healthy volunteers, nine met the inclusion criterion of a rise in body temperature of at least 1.0 degrees C after 100 ng endotoxin (Salmonella abortus equi) as a bolus injection. Serum levels of tumour necrosis factor alpha (TNF) and interleukin-6 (IL-6) were both significantly higher than baseline levels 2 h and 3 h after endotoxin injection. 3 weeks later the nine volunteers were again injected with 100 ng endotoxin and oxpentifylline (500 mg over 4 h) was also infused. There was no rise in TNF levels, though IL-6 levels rose in parallel with body temperature. These data suggest that oxpentifylline blocks the endotoxin-induced synthesis of TNF in man and, therefore, could possibly have beneficial effects in clinical endotoxaemia. PMID- 2574768 TI - Amplification refractory mutation system for prenatal diagnosis and carrier assessment in cystic fibrosis. AB - The amplification refractory mutation system (ARMS) has been applied to prenatal diagnosis and carrier detection of cystic fibrosis. The nucleotide sequence of both alleles of the PstI restriction fragment length polymorphism at the KM19 locus, which displays linkage disequilibrium with cystic fibrosis, has been determined. ARMS enables direct analysis of alleles of this polymorphism in DNA isolated from chorionic villus biopsy or white blood cells. PMID- 2574767 TI - Thyroid hormone receptor expression in the "sick euthyroid" syndrome. AB - To explore the hypothesis that alteration of T3 receptor expression may be an important mechanism controlling the tissue effects of thyroid hormones in the "sick euthyroid" syndrome, specific triiodothyronine (T3) receptor mRNAs were measured in tissues from normal subjects and from patients with liver disease, chronic renal failure, or with multiple organ failure on an intensive care unit (ICU). In all patient groups circulating free thyroxine and free T3 were reduced, while thyroid stimulating hormone remained normal. In patients with liver or renal disease, there were significant increases in levels of both alpha and beta T3 receptor mRNAs in peripheral mononuclear cells (PMNCs); in ICU patients there was a significant increase in beta mRNA. In patients with liver disease increases in T3 receptor mRNAs were not confined to PMNCs but were also found in liver biopsy specimens when levels were compared with those in normal donor liver. After liver transplantation, receptor mRNAs in PMNCs were similar to those in controls; likewise beta mRNA was similar in liver tissue to normal liver. There was, however, persistent elevation in alpha receptor mRNA. Increases in T3 receptor expression in non-thyroidal illness may be responsible for the maintenance of euthyroidism in the face of reduced levels of circulating thyroid hormones. PMID- 2574769 TI - Osteoporosis in early ankylosing spondylitis: a primary pathological event? AB - Patients with severe ankylosing spondylitis of long duration often have spinal osteoporosis secondary to ankylosis and immobility. Bone mineral density of defined regions of the lumbar spine, femoral neck, and carpus was measured in 25 men who met accepted diagnostic criteria for ankylosing spondylitis but had early disease, with normal mobility and no, or very minor, radiological evidence of lumbar spine involvement. Compared with age-matched male controls, patients with ankylosing spondylitis had a significantly lower hydroxyapatite density in the lumbar spine (mean [SD] 0.82 g/cm2 [0.12] vs 0.91 g/cm2 [0.11]) and in the femoral neck (0.83 g/cm2 [0.11] vs 0.92 g/cm2 [0.11]). There was no significant difference in carpal bone mineralisation density. The pattern of bone loss in these patients indicates early loss of trabecular bone in ankylosing spondylitis, possibly from a systemic cause, but biochemical indices of calcium turnover were similar in patients and controls. PMID- 2574770 TI - Of auctions, dilemmas, and blood-letting: models of escalation behaviour. PMID- 2574771 TI - Spasticity. PMID- 2574772 TI - Propafenone: an antiarrhythmic come in from the cold. PMID- 2574773 TI - Oral candidosis in HIV infection. PMID- 2574774 TI - Dying with their rights on. PMID- 2574775 TI - Looking up while going full circle. PMID- 2574776 TI - The quest for an image of man. PMID- 2574777 TI - Use of cyclosporin in psoriasis. AB - In the treatment of severe psoriasis, cyclosporin may achieve improvement or remission at low doses, but relapse usually occurs on withdrawal of treatment. An initial dose of 3 mg/kg per day is recommended. Complete remission should not be the objective, and the role of long-term maintenance cyclosporin therapy is uncertain because of potential side-effects--especially nephrotoxicity, hypertension, and a predisposition to malignancy. Guidelines are proposed for the assessment of such treatment. PMID- 2574778 TI - Nosocomial epidemic of active tuberculosis among HIV-infected patients. AB - In an investigation of a nosocomial outbreak of tuberculosis, 18 HIV-infected inpatients were found to have been exposed to Mycobacterium tuberculosis; active tuberculosis developed in 8, 7 within 60 days of diagnosis of the index case. The patients with lower total lymphocyte and CD4 lymphocyte counts were more likely to get the disease than were those with higher counts. A low score on multiple antigen skin testing was also associated with the development of active tuberculosis. 4 of the 18 patients had a positive tuberculin skin test before exposure to M tuberculosis; none of them subsequently got the disease. PMID- 2574779 TI - Lung cancer mortality and silicosis in Quebec, 1938-85. AB - Men who had received compensation for silicosis in Quebec between 1938 and 1985 were studied up to the end of 1986 to estimate risk of lung cancer mortality. Particular attention was paid to selection biases inherent in the study of such workers. Age-specific and calendar-year-specific mortality rates of Quebec men from 1931 to 1985 were used for comparison. Risk of death from lung cancer in men who had received compensation for silicosis was more than 3 times higher than expected; silicosis may be a strong risk factor for lung cancer mortality. PMID- 2574780 TI - Psychosis and destitution at Christmas 1985-88. AB - Surveys of the destitute were conducted over four successive Christmas periods in Central London, UK. Functional psychosis with hallucinations and/or delusions, either current (19%) or in the past (22%), were associated with extreme social isolation and imprisonment. PMID- 2574781 TI - Clinical trials with oral iron chelator L1. PMID- 2574782 TI - Treating acute lymphoblastic leukaemia after relapse: bone marrow transplantation or not? PMID- 2574783 TI - Oral delivery of insulin. PMID- 2574784 TI - Endothelin concentrations in cerebrospinal fluid in depressive patients. PMID- 2574785 TI - Kikuchi's disease presenting as fever of unknown origin. PMID- 2574786 TI - Fluor: another cardinal sign of inflammation. PMID- 2574787 TI - Spontaneous non-gastrointestinal bleeding associated with diclofenac. PMID- 2574788 TI - Detection of vesico-ureteric reflux. PMID- 2574790 TI - HIV enteropathy. PMID- 2574791 TI - Malingering with AIDS. PMID- 2574789 TI - Human recombinant soluble CD4 therapy. PMID- 2574792 TI - Methadone maintenance programmes and AIDS. PMID- 2574793 TI - Increased sensitivity of immunofluorescence for detection of Pneumocystis carinii. PMID- 2574794 TI - HIV and the epidemiologist. PMID- 2574795 TI - Effect of perioperative blood transfusion on recurrence of Crohn's disease. PMID- 2574796 TI - Fatal oxalic acid poisoning from sorrel soup. PMID- 2574797 TI - Delusions after extracorporeal shock-wave lithotripsy. PMID- 2574798 TI - Oesophageal cancer in China. PMID- 2574799 TI - Treatment of writers' dystonia. PMID- 2574800 TI - Ciprofloxacin resistance and staphylococcal endocarditis. PMID- 2574801 TI - Is reperfusion syndrome a myth? PMID- 2574802 TI - ACE inhibitors after myocardial infarction. PMID- 2574803 TI - Diabetes and schizophrenia. PMID- 2574804 TI - Routine diagnostic testing. PMID- 2574805 TI - Adolescent pregnancy. PMID- 2574806 TI - Clinical research planning. PMID- 2574807 TI - Hyperbaric oxygen for carbon monoxide poisoning. PMID- 2574808 TI - Clinical signs of dehydration in children. PMID- 2574809 TI - Ovulation induction, in-vitro fertilisation, and neural tube defects. PMID- 2574810 TI - Ureaplasma and mycoplasma infections of the central nervous system in preterm infants. PMID- 2574811 TI - Value of ESR in assessment of rheumatoid arthritis. PMID- 2574812 TI - Coverage of MMR vaccine. PMID- 2574813 TI - Effect of race and blood group on the immune response to bacterial polysaccharide and conjugate vaccines. PMID- 2574814 TI - Debrisoquine phenotype and genotype in Chinese. PMID- 2574815 TI - Retraction: human papillomavirus subtype 16b. PMID- 2574816 TI - Advertising by doctors. PMID- 2574817 TI - [A mechanized device for induction soldering]. PMID- 2574818 TI - Competitive idiotype-anti-idiotype enzyme immunoassay for adenosine deaminase binding protein. PMID- 2574819 TI - Anti-idiotypic antibodies that interact with beta-adrenergic catecholamine receptor. PMID- 2574820 TI - Different modes of action of 3-amino-1-hydroxy-2-pyrrolidone (HA-966) and 7 chlorokynurenic acid in the modulation of N-methyl-D-aspartate-sensitive glutamate receptors. AB - The N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors are known to be inhibited by 3-amino-1-hydroxy-2-pyrrolidone (HA-966) and 7-chlorokynurenic acid (Cl-KYN), which act at the glycine-regulated allosteric modulatory center. In this work we show that, in synaptic membranes prepared from rat brain, Cl-KYN and HA-966 inhibit the binding of [3H]glycine. Moreover, Cl-KYN can also completely inhibit the binding of [3H]glutamate to the primary transmitter recognition site for the NMDA receptor, whereas HA-966 only partially reduces this binding. Cl-KYN also abolishes the binding of the NMDA receptor antagonist [3H]3-(2 carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). In contrast, HA-966 increases [3H]CPP binding, affecting the affinity but not the maximal number of binding sites. This increase is inhibited by glycine and Cl-KYN. The binding of [3H] (+)-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate (MK 801), used as an index of NMDA receptor activation, is completely inhibited by Cl KYN but only partially by HA-966. In addition, HA-966, but not Cl-KYN, increases the potency of CPP in inhibiting [3H]MK-801 binding. Our results demonstrate that Cl-KYN and HA-966 differ in their ability to modulate the NMDA receptor, perhaps acting at distinct but overlapping recognition sites. Furthermore, our results suggest that agonist and antagonist recognition sites of the NMDA receptor may be independently regulated by glycine and HA-966, which would result, respectively, in a positive and negative allosteric modulation of the NMDA receptor complex. PMID- 2574821 TI - Regulation of tyrosine hydroxylase activity in rat PC12 cells by neuropeptides of the secretin family. AB - Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, is subject to regulation by the cAMP as well as the calcium and cGMP second messenger systems. Treatment of intact rat PC12 cells with neuropeptides including secretin and vasoactive intestinal polypeptide (VIP) stimulated tyrosine hydroxylase activity 2 to 3-fold in vitro. Secretin (EC50 = 10 nM) was about 3 orders of magnitude more potent than VIP (EC50 = 3 microM). A combination of several protease inhibitors failed to enhance the potency of either peptide. Other members of the secretin family including glucagon and peptide histidine isoleucine (PHI) stimulated tyrosine hydroxylase activity to a lesser extent. Somatostatin, which is not homologous to secretin, was ineffective. The maximal response of tyrosine hydroxylase activation to 1 microM secretin occurred within 6-15 sec. Secretin, VIP, and forskolin also enhanced tyrosine hydroxylase activity (3,4-dihydroxyphenylalanine production) in intact cells, as determined by high performance liquid chromatography and electrochemical detection. Secretin, VIP, PHI, and glucagon increased the levels of cAMP in PC12 cells more than 10-fold, as determined by radioimmunoassay. We also demonstrated that cAMP is released from the cells into the incubation medium following secretin treatment. Secretin and VIP treatment also enhanced the activity of cAMP dependent protein kinase in a concentration-dependent fashion, as measured subsequently in vitro. Based on the greater potency of secretin in comparison with VIP, PHI, and glucagon, we suggest that the PC12 cells contain a secretin preferring receptor that increases cAMP levels and brings about an activation of tyrosine hydroxylase activity through the stimulation of cAMP-dependent protein kinase. PMID- 2574822 TI - Role of intron splicing in the function of the MATa1 gene of Saccharomyces cerevisiae. AB - The MATa1 gene of Saccharomyces cerevisiae is unique in yeast cells in that it contains two short intervening sequences (IVS1 and IVS2) 54 and 51 nucleotides long. The 3' intron is inefficiently spliced and results in the accumulation of transcript with only the first intron removed, leading to the speculation that the gene may produce different protein products by alternative splicing patterns. We have used in vitro mutagenic techniques to construct intronless MATa1 genes and have introduced point substitutions in the 5'-TACTAAC-3' internal conserved sequence of each intron to identify the protein product that is required for repression of haploid-specific genes. Analysis of these constructs for the ability to repress expression of an HO::lacZ fusion and for the ability to allow diploid cells to undergo sporulation during conditions of starvation revealed that the gene is functional with two, one, or no introns and that the only functional protein is the one produced when both introns are spliced from the mRNA. PMID- 2574825 TI - Vertebrate development. Limbs: a pattern emerges. PMID- 2574824 TI - Regulation of type I (epidermal) transglutaminase mRNA levels during squamous differentiation: down regulation by retinoids. AB - Squamous differentiation of rabbit tracheal epithelial cells is accompanied by an approximately 50-fold increase in the activity of type I (epidermal) transglutaminase, while the levels of type II (tissue) transglutaminase remain almost undetectable. To identify a cDNA encoding type I transglutaminase, we screened a library of cDNA clones prepared from poly(A)+ RNA isolated from squamous-differentiated rabbit tracheal epithelial cells. Four overlapping clones (represented by clone pTG-7) which span a range of 2.8 kilobases were identified; partial sequencing of pTG-7 indicated that it encodes a transglutaminaselike protein. pTG-7 hybridized to a 3.6-kilobase mRNA which is distinct from that for type II transglutaminase. pTG-7 mRNA levels were low in proliferative cells, increased dramatically in squamous-differentiated cells, and could be further enhanced by growth of the cells in high concentrations (2 mM) of calcium ions. Retinoic acid, which blocks the expression of the squamous phenotype, prevented this increase in pTG-7 mRNA levels. These changes in levels of pTG-7 mRNA parallel the changes in type I transglutaminase activity observed under similar culture conditions. These data indicate that pTG-7 encodes the mRNA for transglutaminase type I and that expression of this mRNA is negatively regulated by retinoic acid. PMID- 2574826 TI - Palaeontology. Four legs to stand on... PMID- 2574823 TI - Nuclear gene for mitochondrial leucyl-tRNA synthetase of Neurospora crassa: isolation, sequence, chromosomal mapping, and evidence that the leu-5 locus specifies structural information. AB - We have isolated and characterized the nuclear gene for the mitochondrial leucyl tRNA synthetase (LeuRS) of Neurospora crassa and have established that a defect in this structural gene is responsible for the leu-5 phenotype. We have purified mitochondrial LeuRS protein, determined its N-terminal sequence, and used this sequence information to identify and isolate a full-length genomic DNA clone. The 3.7-kilobase-pair region representing the structural gene and flanking regions has been sequenced. The 5' ends of the mRNA were mapped by S1 nuclease protection, and the 3' ends were determined from the sequence of cDNA clones. The gene contains a single short intron, 60 base pairs long. The methionine-initiated open reading frame specifies a 52-amino-acid mitochondrial targeting sequence followed by a 942-amino-acid protein. Restriction fragment length polymorphism analyses mapped the mitochondrial LeuRS structural gene to linkage group V, exactly where the leu-5 mutation had been mapped before. We show that the leu-5 strain has a defect in the structural gene for mitochondrial LeuRS by restoring growth under restrictive conditions for this strain after transformation with a wild-type copy of the mitochondrial LeuRS gene. We have cloned the mutant allele present in the leu-5 strain and identified the defect as being due to a Thr-to Pro change in mitochondrial LeuRS. Finally, we have used immunoblotting to show that despite the apparent lack of mitochondrial LeuRS activity in leu-5 extracts, the leu-5 strain contains levels of mitochondrial LeuRS protein to similar to those of the wild-type strain. PMID- 2574827 TI - Early warning for LTP. PMID- 2574828 TI - Coordinate expression of the murine Hox-5 complex homoeobox-containing genes during limb pattern formation. AB - The homoebox-containing genes of the Hox-5 complex are expressed in different but overlapping domains in limbs during murine development. The more 5' the position of these genes in the complex, the later and more distal is their expression. Antero-posterior differences are also observed. A model is proposed that accounts for the establishment of these expression domains in relation to the existence of a morphogen released by the zone of polarizing activity. Comparison of these observations with the expression patterns of the genes of Hox complexes in the early embryo suggests that similar molecular mechanisms are involved in the positional signalling along the axes of both the embryonic trunk and the fetal limbs. PMID- 2574829 TI - Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes. AB - The lymphocyte function-associated molecule LFA-1 (CD11a/CD18) plays a key part in lymphocyte adhesion. Lymphocytes do not adhere spontaneously; activation of protein kinase C (PKC) by phorbol esters, however, gives rise to strong LFA-1 dependent adhesion, indicating that activation of LFA-1 is required to induce cell adhesion. We have now investigated whether the functionally important CD2 and CD3 surface structures on T lymphocytes are involved in the activation of LFA 1. The stimulation of these molecules, which causes activation of PKC, strongly promoted LFA-1-dependent adhesion. Furthermore, we demonstrate by using cells from an LFA-1-deficient patient that this enhanced lymphocyte adhesion is caused by activation of the LFA-1 molecule and not by activation of its ligands. LFA-1 was persistently activated by triggering through CD2 but only transiently by triggering through CD3. We postulate that CD2 and CD3 can differentially regulate the affinity of LFA-1 for its ligands by modulating its molecular conformation through PKC-dependent mechanisms. PMID- 2574830 TI - Comment on the pain management article. PMID- 2574831 TI - [The effect of the systemic administration of neuroleptics on the neuronal background activity of the ventrolateral thalamic nucleus in the cat]. AB - The background activity of 272 neurons of the ventrolateral thalamic nucleus was registered extracellularly in chronic experiments on cats in drowsy state before and after systemic injection of haloperidol and droperidol in cataleptic doses. In intact animals the neuronal activity was characterized by the burst discharges with short duration (5-50 ms) and high intraburst frequency (200-450/s). In 15% of investigated cells the rhythmic sequences of burst discharges with frequency of 2-2.5, rarely 3-4/s were revealed. After injection of haloperidol and droperidol the amount of neurons with rhythmic activity increased to 22% and 30%, respectively. The predominant burst frequency augmented to 3-5/s. In a third of cells long rhythmic discharges lasting for 80-300 ms were registered. After chronic haloperidol administration (10 days) relatively low intraburst frequency (60-170/s) was observed in 37% of cells. It is suggested that the above changes are a result of strengthening of the inhibitory influences on the ventrolateral neurons from substantia nigra and reticular thalamic nucleus because of blockage of the dopamine and alpha-adrenergic receptors. PMID- 2574832 TI - The antihypertensive effect of atenolol and bopindolol in the elderly. AB - The antihypertensive efficacy and tolerability of two betablockers: atenolol and bopindolol, was compared in a group of 30 elderly subjects aged 64.8 +/- 4.6 years. The daily dose of the two agents was relatively low. Atenolol 50-100 mg and bopindolol 0.5-1.0 mg sufficed to cause reduction of DBP to the target of less than or equal to 95 mm Hg, when applied as monotherapy. This was achieved in 75% of cases with bopindolol and in 93% of cases with atenolol. Atenolol, 50-100 mg/dd, lowered blood pressure from 173.7 +/- 13.2/103.7 +/- 3.0 (weekly) to 155.5 +/- 16.5/86.5 +/- 8.2 mm Hg (week 12) (P less than 0.005) while bopindolol, 0.5 1.0 mg, lowered blood pressure from 171.6 +/- 11.3/104.1 +/- 3.6 to 158.7 +/- 20.9/86.1 +/- 6.0 mm Hg (P less than 0.005). Heart rate was reduced from 80.5 (week 4) to 66.7 +/- 7.3 (week 12) by atenolol (P less than 0.0001), and from 83.7 +/- 11.8 (week 4) to 71.1 +/- 7.5 (week 12) by bopindolol (P less than 0.0001). Between treatment differences: comparisons yielded P values which were not sufficiently low to reject the null hypothesis of no difference between the two treatments. Well-being and short-term memory were not affected by either agent and tolerability of both drugs was good. These findings demonstrate that both bopindolol and atenolol are useful agents for control of hypertension in the elderly. PMID- 2574833 TI - Glial uptake of excitatory amino acids influences neuronal survival in cultures of mouse hippocampus. AB - Several reports have described apparently normal survival and development of hippocampal and spinal cord culture preparations grown in Ham's F-12 medium, which contains 100 microM each of L-glutamate and L-aspartate. As at this concentration these amino acids are neurotoxic, some adaptive mechanism must occur to allow neuronal survival. We have investigated the mechanism underlying such adaptation. Dissociated cultures of mouse hippocampal neurons were grown in either Eagle's minimum essential medium or Ham's F-12 medium, supplemented with 5% horse serum. Analysis of neuronal density in cultures stained for neuron specific enolase showed that although large numbers of neurons were present in mature cultures grown in either medium, neuronal survival in cultures grown continuously in F-12 was reduced to 41% compared to controls grown in Eagle's minimum essential medium. Physiological studies showed that those neurons which survived in F-12 did not lose their sensitivity to excitatory amino acids. In addition, the acute application of fresh, serum-free F-12 to 10-14-day-old cultures grown in either minimum essential medium or F-12 was highly neurotoxic. Three lines of evidence suggest that glial uptake of amino acids, and reduction of the extracellular concentration of glutamate and aspartate below neurotoxic levels, rather than receptor desensitization underlies the adaptive mechanism allowing neuronal survival. First, application of fresh F-12 produced large depolarizations, and profound neuronal swelling in cultures grown in F-12; however, after several hours swelling reversed suggesting a slow onset of the adaptive process. Second, pressure application of conditioned F-12 obtained from sister cultures also elicited depolarizations in neurons grown in F-12, but the amplitude of the underlying inward current was 25-30% of that produced by fresh F 12, suggesting a loss of potency of F-12 exposed to prolonged contact with hippocampal cultures. Third, measurement by high performance liquid chromatography showed reduction of aspartate concentrations to around 10% of those present in fresh F-12, within 24 h after exposing glial cell cultures to fresh F-12. It is concluded that cellular uptake mechanisms for amino acids have a strong impact on excitotoxicity in vitro, and most likely play an important role in protecting neurons from the potentially damaging action of high concentrations of excitatory transmitters in vivo. In addition our experiments help to explain the mechanisms permitting neuronal survival in cultures grown in Ham's F-12 medium, which when applied acutely to mature cultures is strikingly neurotoxic. PMID- 2574834 TI - Light and electron microscopic localization of glutamate immunoreactivity in the supraoptic nucleus of the rat hypothalamus. AB - The distribution of glutamate immunoreactivity was mapped within the supraoptic nucleus of the rat hypothalamus utilizing a specific anti-glutamate antibody. Magnocellular neuroendocrine cells of the supraoptic nucleus showed intense immunoreactivity for glutamate which varied with the conditions of fixation. Within the perikarya, reaction product was found associated with the endoplasmic reticulum but not the mitochondria, Golgi, dense bodies or neurosecretory granules. A relatively high density of glutamate-immunoreactive terminals was found in the supraoptic nucleus. These terminals were less affected by fixation condition and were generally found contacting large, glutamate-immunoreactive processes within the ventral dendritic neuropil of the supraoptic nucleus. The pattern and characteristics of glutamate immunoreactivity in the supraoptic nucleus suggested the presence of two distinct glutamate pools. The magnocellular neuroendocrine cells may contain a large, labile metabolic pool of glutamate. These cells, in turn, appear to receive glutamate synaptic input from a more stable pool consistent with suggestions that glutamate may be used as a transmitter within this system. PMID- 2574835 TI - Ammonia causes a drop in intracellular pH in metabolizing cortical brain slices. A [31P]- and [1H]nuclear magnetic resonance study. AB - [31P]- and [1H]Nuclear magnetic resonance spectroscopy were used to study metabolism in cortical brain slices in the guinea-pig during acute exposure to pathophysiological concentrations of ammonia. Intracellular acidification, measured from the chemical shift of endogenous inorganic phosphate, was observed without any change in cellular energy status or concentrations of lactate, glutamate and glutamine. The initial acidification, which developed over a period of 9 min appeared to be heterogeneous, on the basis of a splitting of the inorganic phosphate resonance in a number of experiments, corresponding to pH changes of 0.07 and 0.27 pH units. Subsequently a homogeneous acidification, of 0.15 pH units, developed by 23 min following exposure to ammonia. Intracellular pH recovered within 6 min after discontinuation of the ammonia load. In the absence of external bicarbonate, intracellular pH was 0.12 units more acidic than in the bicarbonate buffer and ammonia caused a further acidification by 0.16 units. When glutamine synthase inhibitor, methionine sulphoximine, was added, there was a slow fall in intracellular pH. Under these conditions, subsequent addition of ammonia failed to cause acidification directly. Thus acute elevation of ammonia does not lead to a change in cerebral high-energy phosphate or lactate metabolism, but may be associated with a fall in cortical intracellular pH. PMID- 2574836 TI - [Use of vecuronium bromide and atracurium besylate in continuous intravenous infusion in urologic surgery]. AB - The effects of continuous i.v. infusion of atracurium and vecuronium monitored by TOF supplied by an ABM monitor have been compared in 60 patients subdivided into four groups and submitted to anaesthesia with isoflurane for urological surgery interventions. Groups A and V received respectively an initial bolus of 0.5 mg/kg atracurium and of 0.08 mg/kg vecuronium followed immediately by continuous i.v. infusion of 5.5 micrograms/kg/min. Atracurium or 0.9 micrograms/kg/min of vecuronium; recovery of neuromuscular function happened spontaneously. Groups A' and V' differed by virtue of the use of 0.04 mg/kg prostigmin in the recovery phase. Average consumption of atracurium and vecuronium were respectively 5.1 +/- 1.75 micrograms/kg/min (2.6-9.03) and 0.75 +/- 0.20 micrograms/kg/min (0.5-1.2) in groups A-A' and V-V'. In groups A and V Recovery time 25-75" of T1 and TR presented a statistically significant difference (p less than 0.05) in favour of atracurium. In groups A' and V' the same parameters presented a statistically non significant difference (p greater than 0.05). The ratio TI/TR does not vary to a statistically significant extent in the 4 groups. The number of infusion rate variations needed to maintain stable neuromuscular block was lower in the atracurium groups. PMID- 2574837 TI - [A selective antimuscarinic agent: pirenzepine. Review of its pharmacologic and clinical properties]. AB - The heterogeneity of muscarinic receptors has been well supported by differential characteristics between pirenzepine and atropine both in receptor binding and in whole tissue pharmacology studies. Under these conditions pirenzepine has been classified as a selective receptor antagonist with high affinity for M1 receptors. The antisecretory properties of pirenzepine on gastric acid and pepsin secretion may be attributed to the antagonistic activity of the drug on muscarinic M1 receptors of gastric intramural plexuses, whereas the effect on parietal muscarinic M2 receptors seems of less importance. Additional inhibitory mechanisms on gastric secretion may be represented by pirenzepine-induced increase in somatostatin release from gastrointestinal system. Significant cytoprotective properties of pirenzepine have been observed on a variety of experimentally induced peptic ulcerations. This protective activity may be due to pirenzepine-induced increase in gastric mucosal blood flow as well as to the increase in gastric transmural electric potential difference. In accordance with this pharmacodynamic profile of pirenzepine, numerous clinical studies have revealed its efficacy in the treatment of both duodenal and gastric ulcerations. In addition to this, the clinical usefulness of the drug has been demonstrated in Zollinger-Ellison syndrome, in stress ulceration, in acute gastrointestinal bleeding as well as in gastritis, duodenitis and non-ulcer dyspepsia. In most of the studies pirenzepine has been found to be well tolerated with a low incidence of antimuscarinic effects which may occur at salivary, ocular, cardiac and urinary sites. The clinical use of pirenzepine alone or in association with H2 blockers is recommended in the treatment of peptic ulcer patients, in the case of acute gastrointestinal haemorrhage and in patients non responders to H2 antagonists. PMID- 2574838 TI - [Therapy of resistant duodenal ulcer]. AB - Significant progress has been made in the treatment of duodenal ulcers since cimetidine went on the market. Furthermore widespread use of the H2 blockers has enable us to identify a group of patients who take 8-12 weeks to heal, despite effective treatment and who are now known as "slow" or non-responders. In tackling the problem of ulcers resistant to medical treatment, the paper details the possibilities offered by current solutions on the basis of personal experience as well as reports in the literature. The results obtainable by surgery are also assessed with emphasis on the identification of suitable patients for and the appropriate timing of his surgical option. Finally a therapeutic flow-chart providing guidelines for the rational selection of therapeutic strategies that still had to be based on uncodified personal preferences is proposed. PMID- 2574839 TI - Tyrosine hydroxylase immunohistochemistry in the normal and 1-methyl-4-phenyl tetrahydropyridine (MPP+)-treated retina of goldfish. AB - Dopaminergic interplexiform neurons have been identified in the inner nuclear layer of goldfish retina, with tyrosine hydroxylase (TH) immunocytochemistry in whole-mounted retinae and in cryosections. The neurotoxin 1-methyl-4 phenylpyridinium ion (MPP+), which selectively damages dopaminergic neurons in mammals, caused a marked depletion of TH immunoreactivity in goldfish retina. Three days after intravitreal injection, retinae showed no significant decrease in the number of TH-positive neurons. However most of the TH-immunoreactive cell bodies showed an evident depletion of TH immunoreactivity and their processes, ramified in the inner and outer plexiform layers, disappeared almost completely. PMID- 2574840 TI - Effects of calcium antagonists on the evoked release of dynorphin A(1-8) and availability of intraterminal calcium in rat hippocampal mossy fiber synaptosomes. AB - The pharmacological properties of presynaptic calcium (Ca) channels on rat hippocampal mossy fiber synaptosomes were characterized by determining the inhibitory potencies for various classes of Ca antagonists on depolarization induced Ca mobilization and the release of dynorphin A(1-8)-like immunoreactivity (Dyn-LI). Flunarizine and cinnarizine were the most potent inhibitors of both parameters (IC50 values less than 10(-5) M). Gadolinium and omega-conotoxin (omega-CgTx) were also effective inhibitors of Dyn-LI release (IC50 values less than 3 x 10(-5) M), but omega-CgTx only partially reduced the level of cytosolic free Ca. The release of Dyn-LI was relatively insensitive to both the L-type (dihydropyridines, verapamil and diltiazem) and T-type (amiloride and phenytoin) channel blockers. It appears that presynaptic N-type Ca channels make the most substantial contribution to the Ca influx required for the exocytosis of Dyn-LI from hippocampal mossy fiber nerve endings. PMID- 2574841 TI - Folate, colitis, dysplasia, and cancer. PMID- 2574843 TI - [Role of the nurse and the feldsher in primary health care]. PMID- 2574842 TI - [Liver-protective action of silymarin therapy in chronic alcoholic liver diseases]. AB - The effects of silymarin (Legalon) therapy on liver function tests, serum procollagen III peptide level and liver histology were studied in 36 patients with chronic alcoholic liver disease in a six month double blind clinical trial. During silymarin treatment serum bilirubin, aspartate aminotransferase and alanin aminotransferase values have been normalized, while gamma-glutamyl transferase activity and procollagen III peptid level decreased. The changes were significant, and there was a significant difference between post-treatment values of the two groups, as well. In the placebo group only gamma-glutamyl transferase values decreased significantly but to a lesser extent than that in the silymarin group. The histological alterations showed an improvement in the silymarin group, while remained unchanged in the placebo group. These results indicate that silymarin exerts hepatoprotective activity and is able to improve liver functions in alcoholic patients. PMID- 2574844 TI - Migraine, migraine variants, and related headaches. AB - The perspectives on migraine are changing rapidly. Many of the recent findings on migraine are examined. The overlap between migraine and tension headache, which has led to a reappraisal of the treatment of this disorder, is reviewed. Both pharmacologic and non-pharmacologic methods of treating migraine are discussed. PMID- 2574845 TI - Three allele TaqI RFLP for probe 3-21 [D15S10] on chromosome 15q. PMID- 2574846 TI - Two TaqI polymorphisms in the 5' region of the von Willebrand factor (vWF) gene. PMID- 2574847 TI - A polymorphic DNA sequence (174-3.7) on chromosome 19 [D19S58]. PMID- 2574848 TI - PvuII RFLP detected by a human beta ADH cDNA probe. PMID- 2574849 TI - Two RFLPs at the lipoprotein lipase (LPL) gene. PMID- 2574850 TI - A biallelic RFLP of the human alpha 2-C4 adrenergic receptor gene (ADRA2RL2) localized on the short arm of chromosome 4 and encoding the putative alpha 2B receptor is identified with Bsu 36 I, using a 1.5 kb probe (p ADRA2RL2). PMID- 2574851 TI - Isolation and mapping of a polymorphic DNA sequence (CJ52.15) on chromosome 11 [D11S383]. PMID- 2574852 TI - The human HOX gene family. AB - We report the identification of 10 new human homeobox sequences. Altogether, we have isolated and sequenced 30 human homeoboxes clustered in 4 chromosomal regions called HOX loci. HOX1 includes 8 homeoboxes in 90 kb of DNA on chromosome 7. HOX2 includes 9 homeoboxes in 180 kb on chromosome 17. HOX3 contains at least 7 homeoboxes in 160 kb on chromosome 12. Finally, HOX4 includes 6 homeoboxes in 70 kb on chromosome 2. Homeodomains obtained from the conceptual translation of the isolated homeoboxes can be attributed to 13 homology groups on the basis of their primary peptide sequence. Moreover, it is possible to align the 4 HOX loci so that corresponding homeodomains in all loci share the maximal sequence identity. The complex of these observations supports and extends an evolutionary hypothesis concerning the origin of mammalian and fly homeobox gene complexes. We also determined the coding region present in 3 HOX2 cDNA clones corresponding to HOX2G, HOX2H and HOX2I. PMID- 2574853 TI - Structure, expression and chromosomal localization of Zfp-1, a murine zinc finger protein gene. AB - Zinc finger proteins (Zfp) are encoded by a large family of genes present in many organisms including yeast and human. Some of them are transcriptional activators and bind specifically to DNA by zinc mediated folded structures commonly known as zinc fingers. The Drosophila Kruppel (Kr) is a segmentation gene and encodes a zinc finger protein. Using a probe from the finger domain of Kr, we have isolated a structurally related gene Zfp-1 from the mouse. In this paper, we report the complete nucleotide sequence of two cDNA clones and the amino acid sequence deduced from them. The putative Zfp-1 protein contains in addition to 7 zinc fingers, two helix-turn-helix motifs. During murine embryogenesis, the Zfp-1 was found to express at a peak level in day 12 embryos. The ubiquitously expressed Zfp-1 gene is located in the 16q region on mouse chromosome 8, between the uvomorulin and the tyrosine amino transferase genes. PMID- 2574854 TI - A TaqI RFLP in the locus D9S29 on human chromosome 9. PMID- 2574855 TI - A second polymorphism identified by a fragment co-amplified with c-Ki-ras. PMID- 2574856 TI - D13N1--a myc-associated sequence found near the TCR gamma locus on mouse chromosome 13. PMID- 2574857 TI - Identification of three alleles for Mus musculus at the Myhc-a locus which co segregates with Np-2, Tcra and Rib-1 on chromosome 14. PMID- 2574858 TI - A new TaqI RFLP of the human fibronectin (FN1) gene. PMID- 2574859 TI - Goodpasture's syndrome in a patient with two endocrine tumours. AB - We describe the occurrence of two anatomically separate and histologically distinct endocrine tumours of bronchus and pancreas in a 64 year old woman with biopsy and serology proven Goodpasture's syndrome. The association between anti glomerular basement membrane antibody disease and multiple endocrine tumours has not been reported previously; possible pathogenetic mechanisms are discussed. PMID- 2574860 TI - Current management of urinary calculi. AB - Open surgery for the removal of renal and ureteric calculi has been rendered almost obsolete in the last eight years. The development of the extracorporeal lithotripter and the pulsed dye laser has permitted many patients to have their stones treated without anaesthesia on an outpatient basis. PMID- 2574861 TI - Patients' attitudes to benzodiazepine dependence. PMID- 2574862 TI - Link between D1 and D2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain. AB - Dopamine receptor types D1 and D2 can oppose or enhance each other's actions for electrical, biochemical, and psychomotor effects. We report a D1-D2 interaction in homogenized tissue as revealed by ligand binding. D2 agonists lowered the binding of [3H]raclopride to D2 receptors in striatal and anterior pituitary tissues. Pretreating the tissue with the D1-selective antagonist SCH 23390 prevented the agonist-induced decrease in [3H]raclopride binding to D2 sites in the striatum but not in the anterior pituitary, which has no D1 receptors. Conversely, a dopamine-induced reduction in the binding of [3H]SCH 23390 to D1 receptors could be prevented by the D2-selective antagonist eticlopride. Receptor photolabeling experiments confirmed both these D1-D2 interactions. The blocking effect by SCH 23390 was similar to that produced by a nonhydrolyzable guanine nucleotide analogue, and SCH 23390 reduced the number of agonist-labeled D2 receptors in the high-affinity state. Thus, the D1-D2 link may be mediated by guanine nucleotide-binding protein components. The link may underlie D1-D2 interactions influencing behavior, since the link was missing in over half the postmortem striata from patients with schizophrenia and Huntington disease (both diseases that show some hyperdopamine signs) but was present in human control, Alzheimer, and Parkinson striata. PMID- 2574863 TI - Requirement for two DNA polymerases in the replication of simian virus 40 DNA in vitro. AB - DNA polymerase alpha-primase has long been considered the primary, if not sole, replicative DNA polymerase in eukaryotic cells. However, recent experiments have provided indirect evidence that a second DNA polymerase may play a role in DNA replication. To identify cellular proteins necessary for DNA synthesis in mammalian cells, we have been studying the cell-free system developed for the replication of simian virus 40 DNA. In this report, we present direct evidence that a second DNA polymerase is required in addition to DNA polymerase alpha primase complex to obtain efficient replication of simian virus 40 origin containing DNA. This DNA polymerase activity is not affected by monoclonal antibodies that inhibit the activity of DNA polymerase alpha and is relatively resistant to the inhibitor [N2-(p-n-butylphenyl)-9-(2-deoxy-beta-D ribofuranosyl)guanine 5'-triphosphate]. Moreover, the activity of the polymerase is highly dependent upon the accessory protein, proliferating-cell nuclear antigen. These characteristics are consistent with the hypothesis that this second DNA polymerase is DNA polymerase delta. PMID- 2574865 TI - Comparison of homeobox-containing genes of the honeybee and Drosophila. AB - We report the isolation of seven homeobox-containing genes from the honeybee (Apis mellifera). Sequence analysis of all homeoboxes and some flanking sequences showed that six of seven genes are more than 90% identical to their corresponding Drosophila homologues within the homeobox and, with one exception, also in the flanking sequences. The homologues that were identified include three homeotic selector genes [Sex combs reduced (Scr), Antennapedia (Antp), and abdominal-A (abd-A); the two engrailed (en) genes; and the muscle segment homeobox (msh)]. Surprisingly, no homologue of the segmentation gene fushi tarazu was found in the honeybee. For the remaining bee gene, a Drosophila homologue is not known. This indicates that, with some exceptions, structurally homologous genes are involved in the control of bee and Drosophila development, although Hymenoptera differ significantly in their embryogenesis from Diptera and have evolved separately for some 250 million years. PMID- 2574864 TI - Mitochondrial benzodiazepine receptors regulate steroid biosynthesis. AB - Recent observations on the steroid synthetic capability within the brain open the possibility that benzodiazepines may influence steroid synthesis in nervous tissue through interactions with peripheral-type benzodiazepine recognition sites, which are highly expressed in steroidogenic cells and associated with the outer mitochondrial membrane. To examine this possibility nine molecules that exhibit a greater than 10,000-fold difference in their affinities for peripheral type benzodiazepine binding sites were tested for their effects on a well established steroidogenic model system, the Y-1 mouse adrenal tumor cell line. 4' Chlorodiazepam, PK 11195, and PK 14067 stimulated steroid production by 2-fold in Y-1 cells, whereas diazepam, flunitrazepam, zolpidem, and PK 14068 displayed a lower (1.2- to 1.5-fold) maximal stimulation. In contrast, clonazepam and flumazenil did not stimulate steroid synthesis. The potencies of these compounds to inhibit 3H-labeled PK 11195 binding to peripheral-type benzodiazepine recognition sites correlated (r = 0.985) with their potencies to stimulate steroid production. Similar findings were observed in bovine and rat adrenocortical cell preparations. These results suggest that ligands of the peripheral-type benzodiazepine recognition site acting on this mitochondrial receptor can enhance steroid production. This action may contribute specificity to the pharmacological profile of drugs preferentially acting on the benzodiazepine recognition site associated with the outer membrane of certain mitochondrial populations. PMID- 2574867 TI - PreA4 mRNA distribution in brain areas. AB - The A4 amyloid precursor gene of Alzheimer's Disease (PreA4 gene, App gene, PAD gene) gives rise to three different transcripts, which are generated by alternative splicing. The three transcripts are PreA4695, PreA4751 and PreA4770, according to the number of amino-acids in the primary translation product. Previous expression studies did not discriminate between PreA4751 and PreA4770. We have analyzed the distribution of PreA4 transcripts in four cortical brain areas in a way that allows us the selective identification of each transcript. We used a sensitive S1 nuclease protection assay with a probe derived from PreA4770 cDNA. This radiolabeled probe gives rise to three specifically protected DNA fragments, each corresponding to one of the three PreA4 transcripts. These fragments could readily be resolved in a single lane of a denaturing polyacrylamide gel. PreA4 transcripts were quantified by scanning autoradiograms. In younger individuals PreA4695 mRNA is the dominant transcript with 55% (mean values). PreA4770 mRNA is the minor PreA4 transcript with less than 5% and PreA4751 ranges at 40%. The exception is observed in occipital cortex, where PreA4751 (50%) is higher than PreA695 (45%). A different situation was observed in older individuals. In the latter PreA4(695) transcripts are significantly reduced, with the exception of frontal cortex, whereas PreA4770 transcripts show an increase. PreA4751 has a constant level of 45% and becomes the dominant transcript. PMID- 2574866 TI - Receptors for D-Trp6-luteinizing hormone-releasing hormone, somatostatin, and insulin-like growth factor I in MXT mouse mammary carcinoma. AB - Membrane receptors for D-Trp6-luteinizing hormone-releasing hormone (D-Trp6-LH RH), somatostatin-14 (SS-14), and insulin-like growth factor I (IGF-I) were estimated in MXT mammary cancers of mice using sensitive multipoint micromethods. The receptors were characterized in untreated animals and following in vivo treatment with microcapsules of the agonist D-Trp6-LH-RH and the somatostatin analog RC-160, which strongly inhibited tumor growth. In the control group, D Trp6-LH-RH was bound to the single class of saturable, specific, noncooperative receptor sites (Kd, = 29.3 +/- 8.48 x 10(-9) M; Bmax = 4.55 +/- 0.31 pmol/mg membrane protein). Treatment with D-Trp6-LH-RH alone or in combination with RC 160 produced down-regulation of membrane receptors for D-Trp6-LH-RH on MXT mammary tumor cells. RC-160 alone and ovariectomy were without effect on D-Trp6 LH-RH receptors. On the membrane surface of MXT mammary cells, we found one class of high affinity, specific, saturable binding sites for SS-14 (Kd = 4.4 +/- 1.9 x 10(-9) M; Bmax = 0.58 +/- 0.21 pmol/mg membrane protein). Treatment with RC-160 alone or combined with D-Trp6-LH-RH significantly increased both the dissociation binding constant (Kd = 18.6 +/- 3.5 x 10(-9) and 10.1 +/- 0.7 x 10(-9) M, respectively) and the binding capacity (Bmax = 13.98 +/- 1.7 and 21.00 +/- 4.0 pmol/mg membrane protein, respectively). We also found specific binding sites (Kd = 3.01 +/- 0.15 x 10(-9) M; Bmax = 2.24 +/- 0.96 pmol/mg membrane protein) for IGF-I in the membrane fractions of MXT mammary cancers. Chronic treatment with D Trp6-LH-RH and RC-160 alone or in combination, as well as ovariectomy, significantly decreased the dissociation binding constant of IGF-I membrane receptors on MXT mammary cells. Our results strongly suggest an important role of LH-RH, SS-14, and IGF-I in the growth of MXT mammary carcinoma. Changes in characteristics of receptors after treatment with analogs of LH-RH and SS-14 along with tumor growth inhibition provide additional support for the direct effect of these peptides on tumor cells. A possible significance of these findings as applied to a clinical environment is discussed. PMID- 2574868 TI - Neurochemistry of dementia: establishing the links. AB - Neurochemical research in dementia needs to move beyond descriptive inventories of neurotransmitter systems affected in the specific disorders and to link to molecular studies of mechanism and clinical studies of cognition. New advances in Alzheimer's Disease (AD), Huntington's Disease (HD), and Parkinson's Disease (PD) are being guided by models of how nerve cells die in these disorders. Theories of pathophysiology which address the cellular level need to explain the selective vulnerability of neuronal populations in the different diseases. Clinically, the importance of neurochemical studies will be increased by understanding the bridges between neural and cognitive processes. Clinicians are concerned about the nosology of dementias, diagnostic tests, and more effective therapies. The value of neurochemical studies will be enhanced to the extent that they can contribute to understanding and modifying the clinical phenomenology of these disorders. In this paper, we will briefly review what is known about the neurochemistry of dementia but focus most of our attention on establishing the linkage between this level of description and the levels of description which are either "downstream" (molecular biology) or "upstream" (cognition) in terms of a reductionistic conception of understanding the disease process. We will explore how understanding neurochemistry relates to our understanding of disease mechanism and what constraints neurochemical studies place on understanding clinical aspects of disease. We will conclude by briefly discussing some of the problems with our current understanding of the neurochemistry of dementia and how we can address those problems in the future. PMID- 2574869 TI - Study of restriction fragment length polymorphism in the cystatin C gene of elderly patients with dementia and aged Down's syndrome patients. AB - Using a full length cystatin C cDNA probe and the Alu I restriction enzyme a total of 33 patients with senile dementia, Alzheimer type and 31 Down's syndrome patients have been investigated for the presence of the 630 bp Alu I restriction fragment length polymorphism in the cystatin C gene detected in Icelandic patients with hereditary cystatin C amyloid angiopathy. Results showed that all the patients had normal cystatin C fragment length of 600 bp. PMID- 2574870 TI - Introduction to scrapie and perspectives on current scrapie research. AB - Scrapie is the prototype of a family of six transmissible diseases which includes Creutzfeldt-Jakob disease, the only known transmissible human dementia. Bovine spongiform encephalopathy is the most recent addition to the family. Alzheimer's disease is not known to be transmissible. However the pathogenesis of both scrapie and Alzheimer's disease is associated with the modification of (different) normal brain proteins to form various types of amyloid. In scrapie, the evidence suggests that a membrane glycoprotein, PrP, is the precursor of the scrapie associated fibrils (SAF) found in brain extracts, and also of the extracellular deposits of cerebral amyloid which resemble the Alzheimer plaque cores. The host gene that makes PrP is closely linked to the gene Sinc which controls the incubation period of the many different scrapie strains in mice. It is possible that these two genes are the same, i.e., that PrP is the product of Sinc gene. In addition, scrapie infectivity copurifies with modified PrP (SAF). Modified PrP may be the protective protein coat of the independent scrapie genome which some think is a very small nucleic acid. Others believe that the amyloidogenic form of PrP is itself the infectious scrapie agent. Whatever the true situation, there appear to be very short pathways between scrapie infection and amyloidogenesis. PMID- 2574871 TI - Immunoaffinity purification and neutralization of scrapie prions. AB - The scrapie agent causes a degenerative neurologic disease and can be transmitted to laboratory rodents. The unusual properties of the scrapie agent prompted introduction of the term prion in order to distinguish this class of novel pathogens from viruses and viroids. The scrapie prion protein (PrPSc) is the only component of the infectious scrapie prion identified, to date. Although many biochemical and genetic lines of evidence argue that PrPSc is a major component of the infectious particle, the most convincing data is derived from immunoaffinity purification studies. Limited proteinase K digestion of hamster brain PrPSc produced PrP 27-30. After dispersion of brain microsomes isolated from scrapie-infected hamsters into detergent-lipid-protein complexes (DLPC), copurification of PrPSc and scrapie infectivity was obtained with PrP 27-30 monoclonal antibody affinity columns. PrPSc was enriched approximately 5700-fold with respect to total brain protein while scrapie prion infectivity was enriched approximately -4000-fold. The ratio of prion titer to PrPSc remained constant throughout purification. Heterologous monoclonal antibody columns failed to bind either PrpSc or scrapie infectivity. Polyclonal rabbit PrP antiserum raised against sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) purified PrP 27-30 reduced scrapie infectivity dispersed into DLPC by a factor of 100. Our findings represent the first direct immunologic and chromatographic demonstrations of a relationship between PrPSc and prion infectivity as well as providing additional support for the contention that PrPSc is a major component of the infectious scrapie particle. While these results and those of other studies establish that PrPSc is a component of the infectious prion, the possibility of a second component such as a small nucleic acid which might be required for infection must still be considered. PrPSc is encoded by a single copy cellular gene and not by a hypothetical-nucleic acid within purified prion preparations. Normal, uninfected cells express the cellular prion protein (PrPC). Both PrPSc and PrPC appear to be translated from the same 2.1-kb mRNA. The N terminal amino acid sequences of hamster PrPC and PrPSc are identical; both correspond to that predicted by the translated prion protein (PrP) gene sequence. While the chemical difference between PrPC and PrPSc remains unknown, the organization of the PrP gene argues that it results from a posttranslational event. The mouse PrP gene is on chromosome 2 and is linked to a gene controlling the scrapie incubation time (Prn-i).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2574872 TI - PrPSc in scrapie-infected hamster brain is spatially and temporally related to histopathology and infectivity titer. PMID- 2574873 TI - Comparative sequence analysis, in vitro expression and biosynthesis of mouse PrP. AB - A number of studies have indicated that an endogenous brain protein, PrP, is associated with transmissible agents causing spongiform encephalopathies such as scrapie, kuru, and Creutzfeldt-Jakob disease. It has been proposed that PrP derived from scrapie brain is the scrapie agent itself. To test directly whether the PrP mRNA in scrapie brain tissue can encode the scrapie agent, we expressed PrP cDNA cloned from scrapie-infected mouse brain in vitro. The expressed PrP did not transmit scrapie to susceptible mice. Thus either PrP is not the scrapie agent, or the expressed PrP requires additional modification to be infectious. The normal function of PrP is unknown, however, comparison of the amino acid sequences of PrP from mouse, hamster, and human revealed that many structural features of potential functional significance have been conserved during evolution. To learn about normal PrP and whether it is altered by scrapie infection in vitro, we have performed studies of PrP biosynthesis in normal and scrapie-infected mouse neuroblastoma tissue culture cells. The major PrP species were glycoproteins anchored at the cell surface by covalent linkage to phosphatidylinositol. No scrapie-associated modifications of PrP biosynthesis were observed, and, none of the metabolically labeled PrP observed in either scrapie-infected normal cells was resistant to proteinase K. PMID- 2574874 TI - The molecular pathology of scrapie and the biological basis of lesion targeting. AB - Strains of scrapie virus can only be distinguished from the incubation period and neuropathology of the disease they induce in mice of different Sinc genotypes. There are two main aspects of the neuropathology: a spongiosis or degenerative vacuolation associated with the replication of virus, and cerebral amyloid plaques. The relationship between these two is unclear - they can occupy topographically quite different centres in the CNS and the timing of their occurrence is different. Surprisingly this is also the case using the very precise targeting provided by the intraocular infection route. Here the earliest spongiosis is very localised into the primary and secondary projections from the retina, but plaques, when they occur, occupy quite different sites. The relationship between plaques and spongy degeneration is probably a neuroanatomical one, similar to that suggested between plaques and tangle-bearing neurons in Alzheimer's disease. A third aspect of the pathology is the occurrence of SAF in negative-stained E.M. preparations, formed from the aggregation of a sialoglycoprotein called PrP or SAF-protein. Immunolabelling of plaques with antisera to SAF protein shows as yet that there is no antigenic variation in the protein prepared from different scrapie models with different strains of the virus based on available reagents. Strain variation is only recognised on biological criteria; as yet, there are no independent molecular markers or in vitro tests which can account for the biological variation. PMID- 2574875 TI - Bovine spongiform encephalopathy: a scrapie-like disease of British cattle. AB - Scrapie is a CNS degenerative infection of sheep and goats, which is invariably fatal after incubation periods of several months to years. Related disorders are found naturally in man and other species. There is a impairment of protein catabolism in scrapie and related diseases which leads to the accumulation of sparingly-soluble protein deposits in brain. These protein aggregates may share with the amyloid of Alzheimer's disease (AD) some common stage in the biochemical pathways of their formation, although different proteins are affected in scrapie (the PrP protein) and AD (the A4-precursor protein). Recently, cattle with the clinical signs and brain pathology of a neurodegenerative disease have been reported, and this cattle disorder has been called bovine spongiform encephalopathy (BSE). BSE-affected brains contain abnormal forms of the bovine homologue of PrP. This provides biochemical evidence that BSE is cattle scrapie rather than cattle AD. PMID- 2574876 TI - Quantitative constraints on mechanisms of replication for information-carrying prions. PMID- 2574877 TI - Molecular pathology of the amyloid A4 precursor of Alzheimer's disease. AB - The precursor of the Alzheimer's disease-specific amyloid A4 protein is an integral, glycosylated membrane protein which spans the bilayer once. The carboxy terminal domain of 47 residues was located at the cytoplasmic site of the membrane. The three domains following the transient signal sequence of 17 residues face the opposite side of the membrane. The C-terminal 100 residues of the precursor comprising the amyloid A4 part and the cytoplasmic domain have a high tendency to aggregate. This finding suggests that there is a precursor product relationship between precursor and amyloid A4. We suggest that besides proteolytic cleavage, other events, such as membrane damage are primary events that precede the release of the small, aggregating amyloid A4 subunit. PMID- 2574878 TI - Immunoaffinity chromatographic purification of amyloid-related proteins from Alzheimer's disease brain tissue. AB - We describe the preparation and characterisation of an immunoaffinity column of immobilised monoclonal antibody 1G10/2/3 which was raised against a synthetic peptide representing residues 8-17 of the A4 amyloid protein (or beta-protein) of Alzheimer's disease (AD). In previous work we have shown that this antibody reacts in formalin-fixed, paraffin-embedded tissue sections with plaque cores, plaque periphery and cerebrovascular amyloid of AD. We have used the column in the immunoaffinity isolation from extracts prepared from AD brain tissue of a protein with an apparent molecular weight of 31,000; this protein is reactive with 1G10/2/3 in Western blots. The same protein is also present, but at lower level, in normal control brain tissue. Possible relationships of this protein to the predicted structures for full-length A4-precursors are discussed. However, in view of the preliminary nature of the observations and potential problems relating to proteolysis occurring post-mortem or during the extraction process, firm conclusions cannot be drawn about any role for this molecule in the normal functioning of A4-precursors or in the conversion of A4-precursor to the deposits of A4 seen in AD brain. Nevertheless, we conclude that we are seeing a stable but truncated form of A4-precursor and it will be of interest to see if further studies can clarify the possible relevance of the protein to normal or pathological processes in human brain tissue. PMID- 2574879 TI - Amyloid precursor protein in cell cultures: a 130 kDa polypeptide. PMID- 2574880 TI - Extracytoplasmic and A4 domains of the amyloid precursor protein: molecular cloning, genetically engineered cell lines and immunocytochemical investigations. PMID- 2574881 TI - Evolution and extinction. PMID- 2574882 TI - The causes of extinction. AB - A species may go extinct either because it is unable to evolve rapidly enough to meet changing circumstances, or because its niche disappears and no capacity for rapid evolution could have saved it. Although recent extinctions can usually be interpreted as resulting from niche disappearance, the taxonomic distribution of parthenogens suggests that inability to evolve may also be important. A second distinction is between physical and biotic causes of extinction. Fossil evidence for constant taxonomic diversity, combined with species turnover, implies that biotic factors have been important. A similar conclusion emerges from studies of recent introductions of predators, competitors and parasites into new areas. The term 'species selection' should be confined to cases in which the outcome of selection is determined by properties of the population as a whole, rather than of individuals. The process has been of only trivial importance in producing complex adaptations, but of major importance in determining the distribution of different types of organisms. An adequate interpretation of the fossil record requires a theory of the coevolution of many interacting species. Such a theory is at present lacking, but various approaches to it are discussed. PMID- 2574883 TI - Mass extinctions among tetrapods and the quality of the fossil record. AB - The fossil record of tetrapods is very patchy because of the problems of preservation, in terrestrial sediments in particular, and because vertebrates are rarely very abundant. However, the fossil record of tetrapods has the advantages that it is easier to establish a phylogenetic taxonomy than for many invertebrate groups, and there is the potential for more detailed ecological analyses. The relative incompleteness of a fossil record may be assessed readily, and this can be used to test whether drops in overall diversity are related to mass extinctions or to gaps in our knowledge. Absolute incompleteness cannot be assessed directly, but a historical approach may offer clues to future improvements in our knowledge. One of the key problems facing palaeobiologists is paraphyly, the fact that many higher taxa in common use do not contain all of the descendants of the common ancestor. This may be overcome by cladistic analysis and the identification of monophyletic groups. The diversity of tetrapods increased from the Devonian to the Permian, remained roughly constant during the Mesozoic, and then began to increase in the late Cretaceous, and continued to do so during the Tertiary. The rapid radiation of 'modern' tetrapod groups--frogs, salamanders, lizards, snakes, turtles, crocodilians, birds and mammals--was hardly affected by the celebrated end-Cretaceous extinction event. Major mass extinctions among tetrapods took place in the early Permian, late Permian, early Triassic, late Triassic, late Cretaceous, early Oligocene and late Miocene. Many of these events appear to coincide with the major mass extinctions among marine invertebrates, but the tetrapod record is largely equivocal with regard to the theory of periodicity of mass extinctions. PMID- 2574884 TI - Diversification and extinction patterns among Neogene perimediterranean mammals. AB - The best mammalian fossil record during the Neogene of Western Europe is that of the rodents, the most successful and diversified mammal order. The study of origination and extinction during the Neogene (24-3 Ma BP) in one of the best documented areas, Spain and southern France, gives an insight into the dynamics of these communities and indicates the possible nature of the driving forces. Three main periods of time show a high rate of origination: the late Burdigalian (17.5 Ma BP), the early Vallesian (11.5-11 Ma BP) and the early Pliocene (4.2-3.8 Ma BP). Two of these high origination-rate periods are immediately followed by important extinction events during which all cohorts are deeply affected (11.5-11 Ma BP and 4.2-3.8 Ma BP). The most important extinction event seems to occur during the early Vallesian (11.5-11 Ma BP), which probably includes the middle/late Miocene boundary. At the Miocene/Pliocene boundary, and during the early Pliocene, the faunal turnover seems to become faster, inducing a strong decrease of the mean species duration. Whereas the main immigration event, which occurs at 17.5 Ma BP, can be related to other faunal migrations in terms of the closure of the Tethys, as it occurs also in eastern Africa and in southwest Asia, the middle/late Miocene boundary event may have been related to a period of ice growth in the Southern Hemisphere. The extinction event that affects the planktonic foraminifera at 12 Ma BP cannot be chronologically correlated to this southwestern European land-mammal extinction event, because the calibration of the marine fossil record during that time-span has to be precise. Some limited terrestrial faunal exchanges that occur during the Messinian between southwestern Europe and northwestern Africa do not deeply affect the general faunal dynamics. Both allochthonous cohorts of immigrants become rapidly extinct. Several endemic rodent faunas, indicating insular conditions, have been reported from the southern edge of the western European continent from the middle Miocene up to the Pliocene. All show low taxonomic diversity, strong endemism and short survival. Some of them, like those of the Gargano Islands during the late Miocene, underwent peculiar morphological changes and also speciation. The large number of rodent genera coevolving in the Gargano Islands is indicative of the large surface areas of these islands. The general geographic pattern of southwestern Europe during the Neogene may therefore correspond to a large continental province including Spain and southern France with some kind of fast-modifying archipelago on its southern rim. PMID- 2574885 TI - The case for extraterrestrial causes of extinction. AB - The dramatic increase in our knowledge of large-body impacts that have occurred in Earth's history has led to strong arguments for the plausibility of meteorite impact as a cause of extinction. Proof of causation is often hampered, however, by our inability to demonstrate the synchronism of specific impacts and extinctions. A central problem is range truncation: the last reported occurrences of fossil taxa generally underestimate the true times of extinction. Range truncation, because of gaps in sedimentation, lack of preservation, or lack of discovery, can make sudden extinctions appear gradual and gradual extinctions appear sudden. Also, stepwise extinction may appear as an artefact of range truncation. These effects are demonstrated by experiments performed on data from field collections of Cretaceous ammonities from Zumaya (Spain). The challenge for future research is to develop a new calculus for treating biostratigraphic data so that fossils can provide more accurate assessments of the timing of extinctions. PMID- 2574886 TI - Natural extinction on islands. AB - Almost all recent extinction of species or subspecies on islands comes from human activities. On the other hand, in local populations there is much natural extinction and immigration, i.e. turnover, on small islands. Most of this turnover occurs in locally rare species, and attests to the phenomenon of minimum viable population size. The MacArthur-Wilson theory is based on this turnover which, from an ecological point of view, is generally trivial. More useful theories of minimum viable population size are being developed. Rarity is the precursor of extinction, and species can be rare in several ways. Models of these phenomena are still primitive, particularly those that relate habitat availability to population density. Models of interactive communities show phenomena that may be relevant to the understanding of extinction in the geological record. Lotka-Volterra equations indicate considerable sensitivity to invasions, sometimes producing a cascade of extinction. Chemostat equations show that the behaviour of food chains can change dramatically with small changes in parameters, suggesting that small environmental effects can sometimes cause large ecological changes, including extinctions, in interactive biotic communities. PMID- 2574887 TI - The present, past and future of human-caused extinctions. AB - This paper re-evaluates whether we are really at the start of a mass extinction caused by humans. I consider the present, past and future of human-caused extinctions. As regards the present, estimates of extinction rates based on Red Data Books underestimate real values by a large factor, because the books evaluate only those species that have attracted specific attention and searches. Especially in tropical areas with few resident biologists, many poorly known species go extinct without having been the object of specific attention, and others disappear even before being described. A 'green list' of species known to be secure is needed to complement 'red books' of species known to be extinct. As regards the past, it is now clear that the first arrival of humans at any oceanic island with no previous human inhabitants has always precipitated a mass extinction in the island biota. Well-known victims include New Zealand's moas, Madagascar's giant lemurs, and scores of bird species on Hawaii and other tropical Pacific islands. Late-Pleistocene or Holocene extinctions of large mammals after the first arrival of humans in North America, South America and Australia may also have been caused by humans. Hence human-caused mass extinction is not a hypothesis for the future but an event that has been underway for thousands of years. As regards the future, consideration of the main mechanisms of human-caused extinctions (overhunting, effects of introduced species, habitat destruction, and secondary ripple effects) indicates that the rate of extinction is accelerating.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574888 TI - The rise and fall of Homo sapiens sapiens. AB - Human beings have broken the ecological 'law' that says that big, predatory animals are rare. Two crucial innovations in particular have enabled us to alter the planet to suit ourselves and thus permit unparalleled expansion: speech (which implies instant transmission of an open-ended range of conscious thoughts) and agriculture (which causes the world to produce more human food than unaided nature would do). However, natural selection has not equipped us with a long-term sense of self-preservation. Our population cannot continue to expand at its present rate for much longer, and the examples of many other species suggests that expansion can end in catastrophic collapse. Survival beyond the next century in a tolerable state seems most unlikely unless all religions and economies begin to take account of the facts of biology. This, if it occurred, would be a step in cultural evolution that would compare in import with the birth of agriculture. PMID- 2574889 TI - Social stress in guinea pigs. AB - Confrontation studies between eight pairs of two 7-8 months old male guinea pigs, each raised with one female from their 30th day of age, were conducted in an enclosure of 2 m2 in the presence of an unfamiliar female. The opponents were chronically kept together for up to 8 days. When they were not separated after 52 hr, one or (in 1 case) both males fell into a comatose state and died 5-8 days after the onset of the confrontation. Four hr after the onset of the confrontations both opponents showed significantly increased plasma glucocorticoid (CS) titers. At this time as well as 24 hr earlier, prospective winners (PW) and prospective losers (PL) did not yet differ in any physiological parameter measured. Forty-eight hr later, PW were characterized by a low body weight loss, low CS, high testosterone (T) and elevated plasma-catecholamine (CA) values. In contrast, PL showed a high body weight loss, very high CS titers, low T-titers and more elevated CA values than PW. Despite these highly significant differences in physiological parameters, PL and PW did not yet differ in the frequency of any agonistic behavioral element recorded. Seventy-two hr after the onset of the chronic cohabitation, losers began to behave more and more passive, they ceased feeding and drinking and were less and less involved in social interactions. The physiological differences between winners and losers intensified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574891 TI - The Psychiatric Symptom Assessment Scale (PSAS). PMID- 2574890 TI - Responses of hypothalamic paraventricular neurons in vitro to norepinephrine and other feeding-relevant agents. AB - To investigate paraventricular hypothalamic neuronal actions responsible for the effects of neurotransmitters on feeding, and to test the notion that a single population of cells there could account for feeding effects, hypothalamic slices containing the paraventricular nucleus (PVN) were prepared from rats. Electrophysiological responses of individual PVN neurons to feeding-inducing agents norepinephrine (NE) and gamma-aminobutyric acid (GABA), and to anorexic agents serotonin (5-HT) and histamine (Hist) were examined. NE inhibited neuronal activity through alpha 2-adrenergic receptors, and excited through alpha 1 receptors. alpha 2-receptors are known to mediate the behavioral effect of NE. NE inhibited most clearly those neurons that otherwise fired continuously in this type of in vitro preparation. GABA affected the activity of 37% of the neurons tested, primarily by inhibition. The inhibitory action of GABA can be related to its feeding-inducing effect. GABA in PVN can also attenuate excitatory responses and enhance inhibitory responses to NE or 5-HT. 5-HT caused excitatory and inhibitory responses with the former action outnumbering the latter by approximately 3 to 1. Since this would result in a net excitation, it appears that 5-HT in PVN inhibits feeding mainly by exciting neuronal activity. Hist excited 72% and inhibited only 2% of PVN neurons. The excitation was blocked by H1-antagonists, which have been shown to mediate Hist effect on feeding. Comparing across neurons, the inhibitory response to NE was correlated with that to GABA, but not with any responses to 5-HT or Hist. The excitatory responses to Hist correlated with 5-HT responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574892 TI - Subjective symptoms: part of the negative syndrome of schizophrenia? AB - We present the psychometric and clinical psychopathological properties of the SDSS for the assessment of subjective symptoms as applied to various schizophrenic samples. The subjective deficit syndrome has not been obvious to most investigators, in part because the currently available scales, even those assessing negative symptoms, were not designed to capture it. While the subjective deficit syndrome is not specific to schizophrenia, it may explain what is widely observed as a major public health problem, namely, that officially "remitted" patients continue to fail in social and occupational functioning. The understanding of this syndrome is a prerequisite for better management of these remitted schizophrenic outpatients. Future longitudinal studies including outpatients are needed to address these issues further. PMID- 2574893 TI - Efficacy and safety of tiospirone vs. haloperidol and thioridazine in a double blind, placebo-controlled trial. PMID- 2574894 TI - Lactate-lowering effect of dichloroacetic acid: a model for investigation of anxiolytic drugs? PMID- 2574895 TI - The Hillside Akathisia Scale: a new rating instrument for neuroleptic-induced akathisia. PMID- 2574896 TI - Effect of treatment with antidepressants and neuroleptics on human leukocyte beta adrenergic receptors. PMID- 2574897 TI - Benzodiazepine augmentation of neuroleptic treatment in patients with schizophrenia. PMID- 2574898 TI - Choice of rating form for evaluating anxiolytics. AB - The HAM-A has been a popular tool for assessing the anxiety status of patients. However, when studying anxiolytics, HAM-A presents problems. It includes 89 signs and symptoms grouped under 14 major items. Redundant symptoms appear in several items, and different symptoms under the same item may have variable severity, resulting in inconsistent ratings. In addition, evaluation of all 89 symptoms is time consuming and cumbersome, especially when frequent ratings are required in studying patient response to pharmacotherapy. The WARS was specifically designed to quantify symptoms of anxiety for the study of anxiolytics. It contains 12 one word items, expressing all the relevant and commonly occurring psychic and somatic symptomatology relevant to anxiety. Symptomatology due to medication is rated separately on a side-effect scale. The WARS is thus more sensitive in detecting therapeutic changes. Because of its simplicity and lack of ambiguity, the WARS can be accurately and effortlessly completed in studying anxiolytics. PMID- 2574899 TI - Course and outcome in delusional psychoses. A 4-year re-follow-up. AB - The purpose of the study was to examine the 4-year course and outcome in first admitted patients with delusional psychoses, and to compare the findings with those of a 2-year follow-up. The index population comprised 88 patients. At follow-up one-fifth of the patients revealed positive psychotic symptoms, half of the patients had experienced psychotic relapse, and one-fourth had remitted fully. Compared with the findings 2 years before, some statistically significant changes were disclosed: the number of patients with positive psychotic symptoms had decreased, more patients had frequent social contacts, and more patients had good outcome according to the Strauss-Carpenter outcome scale. The findings suggest that some patients need a couple of years to improve from the clinical and social aftermaths. However, in most aspects, the findings of the 2-year and the 4-year follow-ups are comparable and predict poor course and outcome for the majority, while only a minority of the patients manage fairly well. PMID- 2574900 TI - Peroxisomal oxidases: cytochemical localization and biological relevance. AB - (1) alpha-HAOX has a broad substrate specificity. In rat kidney, the enzyme reacts with aliphatic and aromatic alpha-hydroxy acids, in rat liver, however, only with aliphatic ones. (2) The best substrate for the demonstration of alpha HAOX activity in rat and human liver is glycolate. (3) alpha-hydroxy butyric acid is the best substrate in the luminometric assay for the demonstration of alpha HAOX activity in the rat kidney, whereas glycolate is not catalysed by the enzyme. (4) In the proximal tubulus epithelial cells of the rat kidney alpha-HAOX is concentrated in the peripheral matrix of the peroxisomes. PMID- 2574901 TI - Biochemical and pharmacological characterization of somatostatin receptors in rat brain. AB - We have characterized specific receptors for tetradecapeptide somatostatin (SS 14) of rat brain using 125I-labeled Tyr11-SS-14([125I-Tyr11]SS-14) as radioligand. [125I-Tyr11]SS-14 binding was sensitive to time, pH, temperature and ionic strength of the buffer, and was optimal in 50mM HEPES/KOH buffer, pH 7.5, at 25 degrees C for 60 minutes. Scatchard analysis indicated that the rat forebrain membranes had a single binding site with an apparent dissociation constant (Kd) of 0.522 +/- 0.044 nM and maximum binding capacity (Bmax) was 233 +/- 37 fmol/mg protein (mean +/- SEM). Ca2+, Mg2+, Mn2+ and Co2+ had a significant effect on the specific binding, which indicates that these metal ions might affect somatostatin receptor activity in the brain. Among CNS acting drugs, Ca2+ antagonists, antischizophrenic drugs, antidepressants and anticholinergic drugs had relative effects on [125I-Tyr11]SS-14 bindings to rat cerebral cortex membranes. PMID- 2574902 TI - [Acute effects of oral bunazosin-hydrochloride in acute heart failure]. PMID- 2574903 TI - Clinical characteristics of nephropathia epidemica in Sweden: prospective study of 74 cases. AB - Clinical symptoms and laboratory measures of renal and liver function, coagulation, and inflammatory parameters were prospectively studied in 74 hospitalized patients (14-74 years of age) with serologic evidence of nephropathia epidemica. The most common clinical findings were acute onset of symptoms, fever (greater than or equal to 38 degrees C), thirst, headache, nausea, back pain, vomiting, myalgia, and abdominal pain. Twenty-seven patients (37%) had hemorrhagic manifestations, i.e., epistaxis, melena, hematemesis, petechial bleeding, macroscopic hematuria, or metrorrhagia. Disseminated intravascular coagulation developed in four patients. Fifty-one percent had thrombocytopenia. Proteinuria was recorded for all patients, while hematuria and glucosuria were noted for 85% and 58%, respectively. Serum creatinine levels were elevated in 71 (96%) of the patients. Levels of C-reactive protein or erythrocyte sedimentation rates were elevated in all cases, usually to levels found in serious bacterial diseases. Sixty-six (89%) of the patients were followed for up to 7 months, at which time all had recovered clinically. No patient died or required dialysis. We conclude that nephropathia epidemica in Sweden has a clinical picture similar to that of hemorrhagic fevers in other parts of the world, but with a milder course and a better prognosis. PMID- 2574904 TI - Relationship between the prevalence of antibodies to arbovirus and hepatitis B virus in the Vale do Ribeira region, Brazil. AB - 280 students, between 6 and 14 years old, residents in the Iguape county, southern coast of the State of Sao Paulo, were studied in order to identify the existence of a possible association between the prevalence of specific antibodies to the hepatitis B virus and the exposure to haematophagous mosquitoes, evaluated indirectly through the prevalence of antibodies to 17 arboviruses isolated in Brazil. The children were from 4 areas with different topographical characteristics: 89 of the children were from the urban zone of the town of Iguape, 89 were from the peri-urban zone, 30 were from the rural area with extensive banana plantations, and 72 were from the jungle zone. Previous studies had shown significantly higher prevalence of antibodies to different arboviruses in the cultivated zone and the jungle zone, when compared to the urban and peri urban zones of Iguape. The detection of antibodies to the HBV surface antigen (HBs Ag) was done through the radioimmunoassay (Ausab, Abbott Laboratory). The cases considered positive were confirmed through the presence of anti-core HBV antibodies (anti-HBc-EIA Roche). A significantly higher prevalence of anti-HBV antibodies was observed in children from the jungle zone (26/72 = 36.1%) when compared to those from the urban zone (5/89 = 5.6%), peri-urban (6/89 = 6.7%) or from the cultivated zone (0/30 = 0%). The result suggest the existence of a common factor in the dissemination of the arboviruses and the hepatitis B virus, supporting the hypothesis that mosquitoes may play an important role in the HBV transmission in tropical forested region. PMID- 2574905 TI - Disposition of 5-aminosalicylic acid from 5-aminosalicylic acid-delivering drugs during accelerated intestinal transit in healthy volunteers. AB - In eight healthy volunteers accelerated intestinal transit time was induced with bisacodyl, and urinary and faecal excretion of sulphasalazine, olsalazine, 5 aminosalicylic acid (5-ASA), and acetyl-5-ASA was studied after a single oral dose of 3.3 mmol sulphasalazine, olsalazine, Pentasa, and Salofalk and 2.6 mmol of Asacol. The faecal and urinary excretion of acetyl-5-ASA was lowest after intake of sulphasalazine and olsalazine and highest after intake of Pentasa and Salofalk. The figures for Asacol were intermediate. This indicates insufficient release of 5-ASA from sulphasalazine and olsalazine. When the results of this study are compared with those of a previous study without accelerated transit time, the disposition of 5-ASA from all the 5-ASA-delivering drugs is influenced unfavourably by an accelerated gut transit but most pronounced in the case of sulphasalazine, olsalazine, and Asacol. The impaired release from the azo compounds sulphasalazine and olsalazine is a result of far less complete splitting of the diazo bond. PMID- 2574906 TI - Increased serum pepsinogen I and recurrence of duodenal ulcer. AB - To determine whether the serum pepsinogen I (PG I) level would be a suitable marker for selecting patients at risk for duodenal ulcer recurrence and, thus, would benefit from maintenance therapy, we treated duodenal ulcer patients with H2-receptor antagonists. After healing 140 ulcer patients we assessed the recurrence rate at 1 year with and without maintenance therapy. The annual recurrence rates in duodenal ulcer patients with hyper-PGI (95 ng/ml or more), with 66 ng/ml less than or equal to PGI less than 95 ng/ml, and with PGI less than 66 ng/ml were 87.0%, 27.3%, and 17.9%, respectively, when they did not receive maintenance therapy. In patients with hyper-PGI the recurrence rate was significantly lower in patients receiving maintenance therapy than in patients not receiving maintenance therapy, whereas in patients with PGI less than 66 ng/ml the recurrence rate was as low as 20% regardless of maintenance therapy. These results indicate that maintenance therapy with half the dose of H2-receptor antagonist is not required by patients with PGI less than 66 ng/ml, whereas those with hyper-PGI may be good candidates for long-term maintenance therapy. PMID- 2574907 TI - Pathophysiology and treatment of gastro-oesophageal reflux disease. AB - Gastro-oesophageal reflux occurs when the pressure barrier of the lower oesophageal sphincter (LOS) fails due to a low basal pressure (less than or equal to 6 mm Hg), sphincteric relaxations or a noncompensated increase in intragastric pressure. This reflux becomes pathological when it leads to symptoms severe enough for the patient to seek medical help or results in reflux oesophagitis or its complications. Damage to the oesophageal mucosa develops when the balance between aggressive and defensive factors is no longer in equilibrium. The main aggressive factor is acid-pepsin or alkaline bile secretion. Defence against this aggression is based on rapid removal of the refluxate from the oesophagus (oesophageal clearance) and on poorly understood mucosal resistance. The length of time acid is in contact with the oesophageal mucosa is shortened by adoption of an upright position, by swallow-induced oesophageal peristalsis and saliva. Treatment of pathological reflux aims (1) to decrease acid aggression by means of H2-receptor antagonists or proton pump inhibitors; (2) to strengthen the anti reflux barrier and improve oesophageal clearance by prokinetic drugs that increase the LOS pressure and enhance peristaltic contractions; and (3) to boost mucosal resistance by sucralfate or prostaglandin analogues. Initial treatment of gastro-oesophageal reflux disease may be symptomatic provided that there are no alarming symptoms, such as dysphagia, anaemia or weight loss. Usually either H2 receptor blockers or prokinetic drugs are used. Endoscopy is indicated whenever alarming symptoms are present and when there is insufficient symptomatic improvement after a 4-6-week therapeutic trial. Moderate oesophagitis may be treated in the same way.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574909 TI - A review of the effects of long-term acid inhibition in animals. AB - Studies with H2-receptor antagonists have revealed a trophic effect on the gastric mucosa - an effect which has been ascribed to hypergastrinaemia secondary to acid inhibition. Such hyperplasia of oxyntic mucosal cells has also been demonstrated in chronic toxicity studies following profound, long-standing inhibition of gastric acid secretion with omeprazole. The central role of gastrin in this effect was clearly demonstrated in the omeprazole studies, as antrectomy prevented this effect in both rats and dogs. The hyperplasia was fully reversible in both species. The close correlation between serum gastrin and hyperplasia of enterochromaffin-like (ECL) cells in the rat oxyntic mucosa has been demonstrated in a large number of experiments using different means to induce hypergastrinaemia, including administration of exogenous gastrin, treatment with antisecretory drugs and partial fundectomy. The hyperplasia of ECL cells was fully reversible even after 1 year of sustained gastric acid inhibition following treatment with a high dose of omeprazole. Marked long-standing hypergastrinaemia explains the findings of gastric ECL cell carcinoids in the life-long rat toxicity studies with both omeprazole and other inhibitors of gastric acid secretion. PMID- 2574908 TI - The clinical utility and safety of omeprazole. AB - More than 13,000 individuals with duodenal ulcer, gastric ulcer or reflux oesophagitis have now taken part in controlled clinical studies with omeprazole. In duodenal ulcer, treatment with omeprazole, 20 mg daily or more, has resulted in healing rates of 58%-83% after 2 weeks and 84%-100% after 4 weeks. In all of these studies, healing rates with omeprazole have been higher than with either ranitidine or cimetidine. Omeprazole has also had a more pronounced effect on ulcer symptoms. Although the first comparative study on gastric ulcer showed only marginally higher healing rates with omeprazole than with an H2-receptor antagonist, later studies have all shown significantly higher healing rates with omeprazole. Healing rates of the order of 70% or more have been achieved within 4 weeks, rising to over 88% after 8 weeks. Symptom relief has also been faster with omeprazole. In both duodenal ulcer and gastric ulcer, almost every patient can be healed, including those resistant to treatment with H2-receptor antagonists. The influence of omeprazole on the healing of reflux oesophagitis has been investigated in several studies comparing omeprazole with ranitidine. Healing rates have been markedly higher with omeprazole in all studies. These unprecedentedly high healing rates (81%-96% at 8 weeks) have also been accompanied by rapid symptom relief. In clinical studies with omeprazole, no clinically significant side-effects which could be ascribed to treatment, nor indeed any serious side-effects, have been observed, neither have any clinically significant changes in laboratory variables been seen. Furthermore, no pathological changes of the gastric mucosa have been detected after long-term treatment with omeprazole. PMID- 2574910 TI - Omeprazole in the management of refractory duodenal ulcer. AB - In about 5-10% of duodenal ulcer patients, ulcer healing is difficult or impossible to achieve with H2-receptor antagonists. Such patients are considered to have a refractory ulcer. The cause of refractoriness remains unknown. Some patients have high acid secretion or inadequate acid suppression on treatment, but this has not been confirmed by all investigators or in all patients. Abnormalities in mucosal defence presumably exist, but none have as yet been identified. The principal medical therapeutic approach has been to continue suppressing acid or to use mucosal protective agents. Increasing the duration of H2-receptor antagonist treatment at the same dose had little effect, but doubling or trebling the dose improved healing rates in open studies. Markedly higher healing rates occurred when treatment was changed from cimetidine to ranitidine (which is more potent) in open studies, but this was not always confirmed in controlled studies. Adding the anti-muscarinic, pirenzepine, to cimetidine to achieve better acid inhibition, improved healing rates in some controlled studies but not in others. The mucosal protectant, colloidal bismuth subcitrate, proved significantly more effective than H2-receptor antagonist treatment, but the drug is suitable only for short-term therapy. Controlled studies with omeprazole confirmed the results of open studies and proved the product to be superior to continued H2-receptor antagonist treatment in healing refractory duodenal ulcer. Open studies using maintenance treatment with low-dose omeprazole suggest that such therapy is effective in keeping refractory duodenal ulcer healed. PMID- 2574911 TI - Use of omeprazole in the management of reflux oesophagitis resistant to H2 receptor antagonists. AB - Severe reflux oesophagitis, which is resistant to treatment with high doses of H2 receptor antagonists, can be treated successfully with the H+,K+-ATPase inhibitor omeprazole. Experience from more than 3 years of continuous treatment with omeprazole, in doses adjusted to prevent recurrences, has demonstrated its high efficacy in the long-term management of the patients. The use of this drug emphasizes the importance of long-standing, effective, 24-hour acid inhibition for reflux oesophagitis. Fasting gastrin levels increase 2-fold during the initial treatment period but continued treatment does not induce any further elevation. Omeprazole does not induce pathological changes in the endocrine cell population of the gastric oxyntic mucosa, though in some patients an increase in the argyrophilic cell volume density during omeprazole treatment has been reported. Careful surveillance of the safety profile of this drug is continuing. PMID- 2574912 TI - Effects of omeprazole on acid secretion and acid-related symptoms in patients with Zollinger-Ellison syndrome. AB - In the Zollinger-Ellison syndrome, symptoms and complications are due to hypersecretion of acid, and the first therapeutic step is to suppress the acid secretion. Long-term treatment with histamine H2-receptor antagonists was compared with omeprazole treatment. A total of 30 consecutive ZES patients were treated continuously with H2-receptor antagonists. During long-term treatment, a marked tachyphylaxis was noted, more than 50% of the patients had periods of dyspepsia, recurrent ulcers were found in 10 patients and in 16 a decline in the action of the H2-receptor antagonist required a change to omeprazole after a median duration of 36 months. A total of 22 patients were treated with omeprazole. During long-term treatment, the dose could be reduced slightly. Inhibition of acid secretion was maintained in all cases, and none had dyspeptic symptoms. The median duration of treatment was 18 months, with a range of 1-120 months (H2-receptor antagonists) and 27 months with a range of 1-66 months (omeprazole). No side-effects were seen with omeprazole. PMID- 2574913 TI - [Mechanism of dynorphin inhibition on vasoconstriction in vitro]. AB - Bioassay and HPLC detection were used to analyze the mechanism of inhibition of stimulation-induced vasoconstriction by dynorphin 1-13 (D1-13). Bioassay showed that D1-13 inhibited the contraction of rabbit ear artery and mesenteric artery induced by electrical field stimulation with IC50s of 8.5 +/- 1.2 x 10(-8) mol/L (n = 4) and 5.02 +/- 1.3 x 10(-7) mol/L (n = 5), respectively. D1-13 was ineffective in rabbit femoral artery at a concentration even larger than 10(-6) mol/L. D1-13 did not alter the basal tension of the blood vessel, nor the vasoconstriction induced by adding norepinephrine (NE) into the bath medium, and both constriction were markedly inhibited by phentolamine, an alpha-adrenoceptor blocker. With HPLC detection, the contents of NE in the bath medium were significantly reduced by D1-13 (5 x 10(-7) mol/L) from 340.56 +/- 73.13 pg/ml to 76.91 +/- 10.26 pg/ml as compared with control group (P less than 0.05). The effect could be completely reversed by naloxone at a concentration of 10(-6) mol/L (P less than 0.05). The results suggest that D1-13 reduces stimulation induced vasoconstriction probably through a presynaptic inhibition of NE release from the nerve terminals. PMID- 2574914 TI - [The protective effect of endogenous and exogenous somatostatin on monolayer cultured islet B cells damaged by streptozotocin]. AB - Exogenous administration of somatostatin exerted a beneficial influence directly on monolayer cultured islet B cells damaged by streptozotocin (3.0 mmol/L). Six to twelve hours following the pretreatment with somatostatin of 0.025, 0.05 and 0.1 microgram/ml the number of viable cells was significantly increased from 41.13 +/- 0.65 x 10(4) cells/ml (STZ control) to 49.0 +/- 2.0, 53.0 +/- 1.33, 53.38 +/- 1.74 x 10(4) cells/ml, respectively. The ultrastructural appearance of the B cells indicated that with many vacuoles and granules occurred in the cytoplasma of these cells, normal organelles disappeared and the nuclei were obscure in structure. The pretreatment with somatostatin (0.1 microgram/ml) protected the B cells against streptozotocin, with mitochondria, Golgi's apparatus and granules in these cells intact. The destruction of B cells induced by streptozotocin was more severe after adding anti-somatostatin serum to neutralize the endogenous somatostatin in the culture, which was reversed by replenishment of somatostatin. Adding Ca2+ carrier A23187 did not change the protective effect of somatostatin, it seemed that there was no relationship between the protective effect of somatostatin and calcium mechanism. PMID- 2574915 TI - [High and low frequency electroacupuncture analgesia are mediated by different types of opioid receptors at spinal level: a cross tolerance study]. AB - Previous studies have shown that rats subjected to low or high frequency electroacupuncture (EA) stimulation release enkephalins or dynorphins respectively to produce analgesia. This conclusion was tested in the present study by using cross tolerance technique for further analysing their receptor mechanisms. The main results were as follows: (1) In rats subjected to 2 Hz EA for 6 h, there was a gradual decrease in the analgesic effect, leading to a state of tolerance to 2 Hz EA analgesia. These rats, however, still responded to 100 Hz EA. Likewise, rats made tolerant to 100 Hz EA were still effective to 2 Hz EA stimulation, showing not significant cross tolerance between 2 Hz and 100 Hz EA analgesia. (2) Rats made-tolerant to 100 Hz EA analgesia showed a diminished response to intrathecal dynorphin A (1-13), a kappa agonist, whereas the analgesic effect of the delta agonist [D-Pen2, D-pen5] enkephalin (DPDPE) remained intact. (3) Rats made tolerant to 2 Hz EA analgesia showed a cross tolerance to DPDPE, but not to dynorphin A (1-13). Results obtained from aforementioned cross tolerance studies suggest that 2 Hz and 100 Hz EA analgesia are mediated by delta and kappa opioid receptors, respectively, at the spinal cord of the rat. PMID- 2574916 TI - [Effects of bombesin on gastrin, somatostatin, glucagon and acid secretion from isolated rat stomach in vitro]. AB - Effects of bombesin on the secretion of gastric acid and gastro-intestinal hormones were investigated in isolated perfused rat stomach. Bombesin (intra arterial, 2 x 10(-10) mol/L, 0.3 ml/min) stimulated gastric acid secretion from basal 2.50 +/- 0.05 x 10(-1) to 8.40 +/- 1.50 x 10(-1) mEq/min (P less than 0.001). Exogenous addition of pentagastrin did not potentiate this effect of bombesin. Bombesin induced twice releasing of gastrin and somatostatin in portal effluent but inhibited glucagon secretion. The basal releasing rates of these three hormones were 62 +/- 8 pg, 5.9 +/- 1.1 ng, and 0.40 +/- 0.03 ng/min respectively. The peak values of gastrin and somatostatin during bombesin stimulation were 1000 +/- 20 pg and 12.2 +/- 2.0 ng/min respectively, while the nadir value of glucagon was 0.17 +/- 0.05 ng/min. All three responses were dose dependent. These three hormones were all detectable, albeit at much lower concentrations in the pyloric effluent perfusate than they were in the portal effluent. PMID- 2574917 TI - Presynaptic cholinergic inhibition in hippocampal cultures. AB - Activity of hippocampal neurons was recorded in a dissociated culture under patch clamp conditions. Excitatory and inhibitory postsynaptic currents (PSCs) were evoked in response to short pulse application of glutamate to other neurons in the culture dish. These PSCs were suppressed by topical application of acetylcholine (ACh) near the recorded neuron. The dose-dependent effect of the muscarinic antagonist pirenzepine indicates that the effect of ACh is mediated by an M2 receptor. ACh did not affect inward current responses to direct application of glutamate onto postsynaptic neurons. This indicates that ACh may interfere with the release process and not with the postsynaptic response to the neurotransmitter. In some cells, ACh reduced inward Ca currents recorded in the presence of Na and K channel blockers. This effect was atropine sensitive and may underly the reduced PSCs. It is suggested that ACh modulates release of neurotransmitters by reducing presynaptic Ica and thereby reducing evoked PSCs. PMID- 2574918 TI - Submarine atmospheres. AB - Nuclear submariners live and work in an atmosphere composed of approximately 80% naturally occurring nitrogen, 19% oxygen (manufactured aboard ship), and a complex mixture of inorganic and organic contaminants. The concentrations of contaminants exist as a balance between the rates of production from human and operational activities and the rate of removal by engineering systems. The biological effects of inorganic gases, particularly carbon dioxide, have been extensively studied. Investigators are now attempting to define the composition and concentration of volatile organic compounds that accumulate during 90-day submergences. Medical studies have not conclusively shown that crewmembers incur adverse health effects from continuous exposures to the sealed atmospheres of nuclear submarines. PMID- 2574919 TI - [Surgical treatment of cryptorchism in children]. AB - A method of sparing fixation of the testicle in cryptorchidism is described. It was used in 200 children. Good and satisfactory long-term results were obtained in all the patients operated upon. PMID- 2574920 TI - [Therapeutic action and efficacy of electrophoresis of nonselective beta-blockers using sinusoidal modulated currents]. PMID- 2574921 TI - [Prevention of recurrence of peptic ulcers]. PMID- 2574923 TI - [Significance of molecular genetics in leukemia and malignant lymphoma]. PMID- 2574922 TI - [Prevention of recurrence of chronic inflammatory bowel diseases]. PMID- 2574924 TI - [Intensified risk monitoring of new drugs in general practice by the established physician]. PMID- 2574925 TI - [Side effects of cardiac glycosides, calcium antagonists and beta blockers in the secondary data of the legal health insurance]. PMID- 2574926 TI - [Side effects caused by benzodiazepines and sedating neuroleptics--results of comprehensive hospital drug monitoring]. PMID- 2574927 TI - [Umea, my little big city]. PMID- 2574929 TI - Prospective evaluation of human chorionic gonadotropin in the treatment of cryptorchidism. AB - Of 158 boys consecutively referred for undescended testis, 77 were found to have true cryptorchidism. Human chorionic gonadotropin (HCG) was given to 60 boys (63 undescended testes) in a dose of 5,000 U (patient age 4-6 years) or 10,000 U (7-9 years). The parents of seven others preferred direct referral for orchiopexy. Minor side effects occurred in 18 boys. Significant increase in weight increment velocity was seen among 7-9-year-olds. Descent of testis occurred in 59% (95% cl 46-71%), with the incidence significantly higher in the older group. Mobile testes were more likely to descend. At surgery following failed HCG treatment, hernia or hydrocele was unexpectedly found in 77% of cases, and 19% of the testes were ectopic in the superficial inguinal pouch. The risk of repeat orchiopexy was not less than in a previous series of primary orchiopexy. Although surgery could be avoided in approximately half of the patients in this series, it is not yet decisively established if HCG should be used diagnostically or therapeutically. Improved pre-treatment identification of ectopia and hernia is required. PMID- 2574928 TI - [Neuromediator mechanisms of wakefulness and the voluntary behavior of cats]. AB - Properties were studied of neurotransmitter provision of mechanisms of voluntary food-procuring behavior in cats. It has been shown that functional significance of monoamino- and cholinergic brain structures in these mechanisms are greatly determined by their participation in the control of the alertness level, the raising of which is necessary for solving complicated tasks and mastering new motor habits by animals. PMID- 2574930 TI - [Effect of somatostatin and ranitidine in acute hemorrhage of the upper digestive tract]. AB - The effects of Somatostatin and Ranitidine were studied in 46 patients with acute hemorrhages of the upper digestive tract, 23 were medicated with Somatostatin, 12 with acute gastric hemorrhages of medicamental etiology and 11 with ulcers. The doses was 500 micrograms bolus and than infusion of 250 micrograms/h. 23 patients were treated with 300 mg/day I.V. of Ranitidine, 12 had acute gastric hemorrhages also of medicamental etiology and 11 with ulcers. Somatostatin stopped the bleeding in 100% of the patients with hemorrhagic gastritis, meanwhile Ranitidine only in 76%. This is statistically significative (p less than 0.04648). Hemorrhages in patients with ulcers were stopped by Somatostatin in 73% and by Ranitidine in 64%. This is not statistically significative (p = 0.4995). No collateral effects were observed in both groups of patients. PMID- 2574931 TI - Kinetic and end-point microdensitometry (section biochemistry) of gamma-glutamyl transpeptidase and dipeptidyl peptidase IV in the mature mouse decidua and visceral yolk sac. AB - gamma-Glutamyl transpeptidase (EC 2.3.2.2) and dipeptidyl peptidase IV (EC 3.4.14.5) were measured in mature mouse decidual and visceral yolk sac epithelial cells by means of kinetic (continuous) and end-point (static) microdensitometry (section biochemistry). For continuous measurements a new device for starting the enzyme reaction allowed the first readings to be made already during its very early phase. Since the initial reaction rates of both peptidases were very different in the plasma membrane of decidual and also in the visceral yolk sac epithelial cells, it was difficult to select a sufficient number of cells of the same activity for representative measurements on the basis of kinetic microdensitometry. Static section biochemistry was performed also for statistical reasons, i.e., in order to obtain information about the distribution of the activities of the decidual and visceral epithelial cells and the number of measurements required to guarantee valid data. Various groups of decidual and visceral yolk sac epithelial cells with different gamma-glutamyl transpeptidase and dipeptidyl peptidase IV activities were formed. In this way, different activities of gamma-glutamyl transpeptidase were measured in the plasma membrane of the cells of the antimesometrial, intermediate, and mesometrial decidua. Compared with dipeptidyl peptidase IV, gamma-glutamyl transpeptidase was significantly more active in the plasma membrane of the antimesometrial decidual cells and microvillous zone of the visceral yolk sac epithelial cells. PMID- 2574932 TI - Amphetamine stereotypy in cats and neurotransmitter interactions in the caudate nucleus. III. Effects of intracaudate injections of quipazine, cyproheptadine and electrical stimulation of the raphe dorsal nucleus. AB - The effect of quipazine and cyproheptadine injected into the rostrodorsal part of the caudate nucleus on spontaneous and amphetamine-induced stereotyped behavior was investigated in free moving cats. Quipazine increased focused and even more locomotor (non-focused) stereotyped behavior, augmented the contralateral head movements and decreased the ipsilateral ones. Cyproheptadine decreased focused stereotypy but increased locomotion and the ipsilateral head movements. These results suggest that the serotonin (S-HT) innervation in the region investigated (rostrodorsal caudate nucleus) has an action synergic with that of dopamine released by amphetamine, i. e. if the inhibitory DA receptors prevail over the excitatory ones in this part of the caudate nucleus, the 5-HT receptors are probably also inhibitory. However, electrical 10-Hz stimulation of raphe dorsal nucleus (RD) induced a short-term decrease in all stereotyped movements. This findings suggest that the 5-HT innervation of the caudate nucleus has a much more complex character and that the influences from RD could be different from those of treatments which stimulate the 5-HT receptors (at least in the rostrodorsal part of the caudate nucleus). PMID- 2574933 TI - Central temperature effects of the transmitter amino acids. AB - Experiments were carried out to determine the temperature changes induced by the transmitter amino acids gamma-aminobutyric acid (GABA), taurine and glycine (representatives of the inhibitor class of amino acids), and of L-glutamic acid and L-aspartic acid (representatives of the excitatory functional class of amino acids). The amino acids were introduced directly into the preoptic anterial part of the hypothalamus (PO/AH). The experiments were made on male Wistar rats into which cannules were implanted in advance in PO/AH using a stereotaxic apparatus and coordinates of administration after Konig and Klippel. At ambient temperature of 22 degrees C GABA and taurine are found to cause a dose-dependent hypothermal response, L-aspartic acid and L-glutamic acid lead to dose-dependent hyperthermia, while glycine does not change the body temperature. PMID- 2574934 TI - Dipeptidyl(amino)peptidase IV and post proline cleaving enzyme in cultured endothelial and smooth muscle cells. AB - Dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) and post proline cleaving enzyme (PPCE; EC 3.4.21.26) can convert or degrade vasoactive peptides and have been identified in isolated vessels. The present study examined the cellular (endothelial/smooth muscle) localization of vascular DAP IV and PPCE. Membrane bound DAP IV was higher on cultured hog aorta smooth muscle (11.7 +/- 1.7 nmol/min/mg) than on endothelium (1.5 +/- 0.3 nmol/min/mg). In contrast, comparable levels of cytosolic PPCE were found in endothelium and smooth muscle (1.5 +/- 0.3 and 1.8 +/- 0.3 nmol/min/mg, respectively). DAP IV was specifically inhibited by diprotin A (Ile-Pro-Ile) (IC50 = 6 microM) while PPCE was inhibited by TPCK. Neither enzyme was affected by o-phenanthroline or inhibitors of aminopeptidase M (amastatin, bestatin), neutral endopeptidases (phosphoramidon), carboxypeptidases N (MERGETPA) or ACE (captopril). DAP IV may play a role in the extracellular metabolism of peptides at or near endothelial and smooth muscle cell surface receptors. In contrast, the cytosolic localization of PPCE may limit its participation to intracellular peptide metabolism. PMID- 2574935 TI - Eastern equine encephalomyelitis virus: epidemiology and evolution of mosquito transmission. PMID- 2574936 TI - Treatment of bovine leukaemia virus-infected sheep with suramin: an animal model for the development of antiretroviral compounds. AB - Bovine leukaemia virus (BLV) and the human T-cell leukaemia/lymphoma viruses I and II represent a specific group of type-C RNA tumour viruses characterized by the presence between the err gene and the 3'LTR of an "x" region or LOR frame, which codes for a protein that trans-activates the transcription of the viral genome. As BLV can also infect sheep and induces pre B-cell specific tumours in these animals, we were interested in investigating whether suramin, a potent inhibitor of retrovirus-associated reverse transcriptase, may inhibit the in vivo multiplication of BLV in sheep. The sheep were infected with 4 X 10(7) leukocytes from a BLV-infected cow. The animals were maedi-visna virus-negative. Viral p24 antigen and reverse transcriptase appeared at 2 weeks and seroconversion occurred at 4 weeks after infection. Suramin was administered at 20 mg/kg/week from the 10th till the 16th week after infection. During the treatment period the expression of p24 antigen as well as the titre of anti-p24 and anti-gp51 antibodies were followed. Suramin treatment led to a significant, but transient, disappearance of p24 antigen and did not affect the titre of anti-p24 and anti gp51 antibodies. The BLV-infected sheep may serve as a useful animal model for the investigation of retrovirus inhibitors and the evaluation of different therapeutic regimens. PMID- 2574937 TI - Expression of the Epstein-Barr virus (EBV) receptor on the surface of cells infected with EBV derived from nasopharyngeal carcinoma. AB - An Epstein-Barr virus (EBV) genome-positive epithelial hybrid cell line, NPC-KT, derived from the fusion of primary nasopharyngeal carcinoma cells with a human epithelial cell line of adenoid origin and a subline of EBV genome-positive Ramos cells, Ramos/NPC, converted after infection with NPC-KT EBV have been previously described (Takimoto et al., 1984; Takimoto et al., 1987). The NPC-KT cells produce virus (NPC virus) with both transforming and lytic properties. In this study, NPC-KT and Ramos/NPC cells were examined for the presence of the EBV receptor as measured by the capacity to absorb radio-labelled P3HR-1 and NPC viruses. It was determined that only P3HR-1 virus can attach to NPC-KT cells. Also, the relative concentration of NPC virus receptors on Ramos/NPC cells was found to be significantly reduced when compared to EBV genomenegative Ramos cells, whereas the relative concentration of receptors for P3HR-1 virus was similar to parental Ramos cells. The results suggest that there are differences at least in part of the receptors for P3HR-1 and NPC viruses. PMID- 2574938 TI - Atypical human rotaviruses in the G.D.R. AB - Following the aetiologic agent of diarrhoea in children aged one to three years we found in the stools a large number of rotaviruses by electron microscopy (EM), although ELISA was negative; the sensitivity of ELISA had been confirmed in previous investigations. In 141 children with diarrhoea 10 conventional (group A) and 21 antigenically distinct rotaviruses were detected. The presence of atypical rotaviruses could be confirmed by electrophoretic analysis of their RNA migration profiles. The electropherotype pattern corresponded to the group C rotaviruses reported by others. PMID- 2574940 TI - Partial replacement of serum with peptone and lactalbumin hydrolysate for the production of foot-and-mouth disease vaccine in BHK-21 cells. AB - Two batches of experimental media were prepared with Difco-Peptone and Centron Peptone in combination with lactalbumin hydrolysate (LAH) in Eagle's salts containing 3 amino acids, vitamins and 1% bovine serum. Both medium batches supported the growth of Razi BHK-21 cells in serial passages and the replication of foot-and-mouth disease (FMD) virus type "A". The infectivity and complement fixing antigen (CFU) titres of the virus were comparable with those in Eagle's medium. The protection indices "C" of the experimental batches of vaccine were highly satisfactory. The experimental media saved up to 90% of serum in comparison with Eagle's medium. PMID- 2574939 TI - Evidence for Hantavirus disease in Slovenia, Yugoslavia. AB - In Slovenia, North-Western part of Yugoslavia, 17 clinically documented Hantavirus disease cases (HVD) were serologically confirmed so far. Previously HVD was reported in the Southern part of Yugoslavia. By the indirect fluorescent antibody test (IFA), the prevalence of IgG class antibodies against different Hantaviral antigens was demonstrated in human sera collected in Slovenia. Three different reactivity patterns were observed. Majority of the IFA-positive human sera were confirmed by the immunoblot method. The distribution of Hantaviral infections was examined in small mammals captured in two natural foci of HVD, where clinical documented cases were reported. Hantaviral antibodies and antigens were demonstrated in C. glareolus, A. flavicollis, A. sylvaticus, and M. musculus. PMID- 2574941 TI - Antibodies to Epstein-Barr virus-induced early antigens in blood donors. AB - IgG class antibodies to the early antigen complex (EA; D + R components) of the Epstein-Barr virus (EBV) were found by indirect immunofluorescence in titres greater than or equal to 1:10 in 196 (49.4%) out of 397 blood donors and titres greater than or equal to 1:20 in 84 (21.2%) of these subjects. Anti-EA titres of greater than or equal to 1:2560 were detected in 6 sera, anti-EA(D) only in 17 donors (4.3%). Additional EBV-specific antibody tests were performed in sera with anti-EA-IgG titres of greater than or equal to 1:20 (n = 84), including IgM class antibodies to virus capsid antigen (anti-VCA-IgM). Specific IgM revealed active EBV infection in 12 blood donors. There was no correlation between the presence of anti-VCA-IgM and the magnitude of anti-EA-IgG titres. Therefore, it seems to be impossible to define the threshold titre for EA antibodies indicating active EBV infection. For this purpose probably a titre increase should be demonstrated in paired sera. PMID- 2574943 TI - Biological profile of a virus belonging to California encephalitis complex isolated in Karelian Autonomous Soviet Socialist Republic. AB - We investigated in white mice and in Syrian hamsters the pathogenesis of infection with a virus belonging to the California encephalitis complex isolated in the Karelian Autonomous Soviet Socialist Republic. The pathogenic properties of the virus were investigated also in green monkeys. The localization and character of lesions in the organs of given animals appeared to be similar. The virus appeared to possess neurotropic activity, it propagated in the animal body by haematogenous route. The virus was found to be heat-resistant and pH sensitive. PMID- 2574942 TI - Pathogenicity of Ife virus for Swiss albino mice. AB - Pathogenicity of Ife virus was studied in Swiss albino mice following four inoculation routes. Mice of all ages survived oral infection without seroconversion; subcutaneous (i.c.) and intraperitoneal (i.p.) infections lead to low titre antibody production. Only suckling mice (1-5 days old) succumbed to intracerebral (i.c.) inoculation with infectivity titres which decreased by age and average survival time (AST) increasing with age. Following i.c. inoculation to suckling mice, the brain infectivity titres increased progressively by days post-infection (p.i.). Virus was not recovered from the lungs and kidney but in low titre it was obtained from the liver, spleen, heart and blood at different days p.i. All organs examined showed evidence of complement fixing and immunofluorescent Ife virus antigen. No gross lesions were observed. The histopathological lesions were limited to the brain. PMID- 2574944 TI - Methods for purification of Rickettsia prowazekii separated from the host tissue: a step-by-step comparison. AB - Two methods for purification of Rickettsia prowazekii strains E, E Vir, and Breinl grown in chick embryo yolk sacs are described. These methods combine either differential centrifugation or sucrose mix, centrifugation through sucrose cushion, 10 mmol/l MgCl2 treatment, filtration through a glass filter AP-20 and 2 cycles of verografin discontinuous density gradient centrifugation. The purification procedure including sucrose mix allowed to recover about 38-42% biologically active rickettsiae, a yield which was by 10% higher than that obtained by the method beginning at differential centrifugation. The rickettsiae free of host cell components preserved their infectious activity. The obtained biomass was suitable for immunological and biological characterization of Rickettsia prowazekii and for isolation of its total DNA. PMID- 2574945 TI - Antibodies to axonal neurofilaments in Creutzfeldt-Jakob disease and other organic dementias. AB - Antibodies reacting with neurofilament proteins were detected by indirect immunofluorescence in the sera from 6 out of 10 patients with verified Creutzfeldt-Jakob disease (CJD), in 4 out of 8 cases of Alzheimer's disease (AD), in a variable percentage (29.4-42.8%) of sera from patients (n = 46) with other dementias of organic or infectious origin and in 5 out of 30 asymptomatic relatives of CJD patients. The occurrence of this antibody did not correlate with the duration or with any other clinical manifestation of CJD. The applicability of the test as differential-diagnostic marker appears limited. The later development of CJD and mental or nervous disease in 3 of 5 asymptomatic relatives with positive serological reaction suggest that the method although nonspecific, may be of certain value in the search for persons at higher risk to develop a degenerative disorder of CNS. PMID- 2574946 TI - The Epstein-Barr virus receptor on two nasopharyngeal carcinoma model cell lines. AB - It was reported that the OKB7 monoclonal antibody to C3d receptor could directly inhibit Epstein-Barr virus (EBV) attachment to and infection of B-lymphocytes. So we tested whether the OKB7 could inhibit superinfection of two epithelial NPC model cell lines (D98/HR-1 and NPC-KT) with EBV. Pretreatment of B-lymphocytes with the OKB7 significantly inhibits EBV infection. However, pretreatment with the OKB7 had no effect on superinfection of D98/HR-1 and NPC-KT cells. These data suggest that an EBV receptor, unrelated to C3d receptor, exists. PMID- 2574947 TI - Combined protective action of nonimmune splenocytes and antiviral antibodies during experimental poliomyelitis (type II) virus infection in mice. PMID- 2574948 TI - Experimental infection of squirrels Sciurus vulgaris by monkey pox virus. PMID- 2574949 TI - Sympathetic nervous system during converting enzyme inhibition. AB - Angiotensin II can stimulate the sympathetic system and inhibit vagal (parasympathetic) outflow under experimental circumstances in animals. Blockade of angiotensin II formation by angiotensin-converting enzyme (ACE) inhibitors might therefore be expected to result in a reduction of sympathetic activity and enhanced parasympathetic activity. Whether this is so in normotensive or hypertensive humans and in human cardiac failure is unclear, since available techniques for recording activity of the sympathetic and parasympathetic systems are imperfect. Nevertheless, most evidence that comes from measurements of venous norepinephrine suggests that the ACE inhibitors have little or no effect on sympathetic activity in normotension and hypertension, although the activated sympathetic system in severe cardiac failure is probably suppressed. It appears that the ACE inhibitors have a parasympathomimetic action that may contribute to the hemodynamic effects of these drugs. Additional information using direct recordings of sympathetic traffic or measurements of norepinephrine "spillover" is needed to clarify the effects of ACE inhibitors on the sympathetic system. PMID- 2574950 TI - Treatment of oophorectomized guinea pigs with intrauterine 17 beta-estradiol pellets may modulate myometrial beta-adrenergic receptor binding properties. AB - Intrauterine 17 beta-estradiol pellets can induce an up-regulation of guinea pig myometrial beta-adrenergic receptor density and l-isoproterenol-dependent adenylate cyclase activity. Does 17 beta-estradiol influence the ability of beta adrenergic receptors to form a "high affinity" state with l-isoproterenol, which is a necessary step for adenylate cyclase activation? Nonpregnant, oophorectomized guinea pigs received intrauterine pellets of either placebo, 17 beta-estradiol, progesterone, or 17 beta-estradiol plus progesterone for 1 week. 17 beta-Estradiol resulted in pharmacologic, whereas progesterone resulted in physiologic plasma 17 beta-estradiol and progesterone concentrations, respectively. The affinity of myometrial beta-adrenergic receptors for l isoproterenol was measured by percentage of inhibition of -[125I]cyanopindolol binding. In all groups, the competition curves in the presence of magnesium chloride could be resolved into two affinity states of the beta-adrenergic receptor, "high" and "low," respectively. The ratio of their dissociation constants was not influenced by hormonal treatment. However, the relative concentration of beta-adrenergic receptors in the high affinity state was significantly higher in the 17 beta-estradiol-treated group than that in the control group. This correlates with the up-regulation in myometrial adenylate cyclase activity and suggests that myometrial beta-adrenergic receptor-adenylate cyclase function may be modulated by 17 beta-estradiol. PMID- 2574951 TI - Pregnancy-induced changes in the interaction of guinea pig myometrial beta adrenergic receptors with l-isoproterenol. AB - The ability of myometrial beta-adrenergic receptors to form a "'high-affinity state" with beta-adrenergic receptor agonists might be greater in pregnant guinea pigs at greater than or equal to 0.9 of gestation than in nonpregnant animals. To determine whether this difference is due to pregnancy in general or is associated only with late pregnancy and to determine whether it persists in the postpartum period, we studied the interaction of l-isoproterenol with beta-adrenergic receptors in myometrial membranes obtained from nonpregnant (nulligravid) animals, pregnant (primigravid) animals at 0.3, 0.7, and 0.9 to 1.0 of gestation (term 65 days), and postpartum guinea pigs (2 to 3 days). The affinity of myometrial beta-adrenergic receptors for l-isoproterenol was measured by percent inhibition of -[125I]cyanopindolol binding. In the presence of magnesium chloride, the competition curves could be resolved into two affinity state of the beta-adrenergic receptor, "high" and "low," respectively, in all groups. The ratio of the dissociation constant of the "low"-affinity state to that of the "high"-affinity state was significantly higher in pregnant guinea pigs at greater than or equal to 0.9 of gestation than in nonpregnant or postpartum animals and in pregnant animals of earlier gestations. In the presence of guanosine triphosphate only one (low-affinity) state of the receptor was detectable. Thus it is only in pregnant guinea pigs at greater than or equal to 0.9 of gestation that the ability of myometrial beta-adrenergic receptors to form a high-affinity state is enhanced. PMID- 2574952 TI - Effects of glucagon on H(+)-HCO3- transport in Henle's loop, distal tubule, and collecting ducts in the rat. AB - Paired micropuncture experiments were carried out in somatostatin-infused volume expanded rats to examine the effects of a glucagon infusion (0.05 ng.min-1.g body wt-1) on urinary acidification and tubular handling of bicarbonate. Whole kidney and single-nephron glomerular filtration rate were not affected by glucagon. In thyroparathyroidectomized (TPTX) rats, glucagon inhibited the reabsorption of total CO2 in Henle's loop. In intact animals, however, the latter effect was not observed. In the distal tubule accessible to micropuncture, net total CO2 absorption was observed during volume expansion plus somatostatin infusion, which reversed to net total CO2 secretion during glucagon infusion in Wistar rats; thus the late distal delivery of total CO2 increased almost 80%. Marked inhibition of urinary acidification occurred in all animals as evidenced by a rise in urine pH and bicarbonate excretion. Conversely, a somatostatin infusion, which decreased the plasma glucagon concentration, stimulated net total CO2 absorption along the distal tubule and augmented final urine acidification in Wistar rats. Finally, urine-minus-blood PCO2 during alkaline diuresis was significantly reduced by glucagon infusion in bicarbonate-loaded TPTX rats. We conclude that 1) glucagon inhibits bicarbonate absorption in superficial Henle's loop in TPTX but not in intact rats, and 2) glucagon stimulates bicarbonate secretion and/or inhibits proton secretion in the distal tubule and collecting ducts, which leads to reduced urinary acidification. PMID- 2574954 TI - Alcohol and drug abuse in treated alcoholics: a comparison of men and women. AB - A survey of 229 male patients and 198 female patients who met lifetime DSM-III criteria for alcohol abuse or dependence was carried out in Toronto, Canada. The patients were evaluated with the National Institute of Mental Health Diagnostic Interview Schedule and other substance abuse rating scales. The prevalence of individual alcohol and drug symptoms, the patterns of abuse, and the prevalence of drug disorders were compared in the two sexes. The study patients were younger than previous treatment samples and were more likely to have other drug disorders. While the overall prevalence of drug disorders was similar in male and female alcoholics, women were more likely to abuse sedatives and minor tranquilizers while men were more prone to the abuse of cannabis and tobacco. Men continue to be more likely to have social and occupational problems resulting from alcohol abuse, to start abusing alcohol earlier in their lives, to have been abusing for longer, and to report higher quantity and frequency of alcohol consumption. With one or two exceptions, the sexes do not differ on other indicators of pathologic use, withdrawal or tolerance, medical sequelae or treatment history. While men have significantly more alcohol problems than women, as measured by the DIS and the MAST, these differences disappear when length of alcohol abuse history, antisocial personality disorder and employment status are controlled for. Similarly, when these variables are controlled for, women exhibit more symptoms of alcohol dependence as measured by the ADS. Women alcoholics come into treatment earlier in their alcoholic careers. PMID- 2574955 TI - [Epidemiology of Parkinson disease]. PMID- 2574953 TI - Unmasking sensitive alpha 2-adrenoceptor-mediated renal vasoconstriction in conscious rats. AB - Renal vascular reactivity to intrarenal arterial boluses of norepinephrine (NE), phenylephrine (PHE; alpha 1-agonist), and guanabenz (GBZ; alpha 2-agonist) was assessed in conscious, freely moving, chronically instrumented, normotensive Wistar rats. Dose-response curves (DRCs) were obtained in the absence and cumulative presence of propranolol (PROP; beta-antagonist), corynanthine (CORY; alpha 1-antagonist) and idazoxan (IDX; alpha 2-antagonist) to estimate effective dosages (ED) required for 15 and 75% peak reductions in renal blood flow. The PHE DRC had a short shallow ED15 region, but was primarily linear with a steep slope. The GBZ DRC had a shallow slope. The NE DRC had a prolonged shallow phase in the ED15 region and a steep slope in the ED75 region. PROP had no effect on the DRCs. CORY caused a parallel rightward shift of the PHE DRC and had no effect on the GBZ DRC. After CORY, the shallow ED15 portion of the NE DRC was even more pronounced with a slope now identical to that of the GBZ DRC, whereas the ED75 region of the NE DRC was shifted rightward like the PHE DRC. IDX preferentially antagonized the ED15 regions of the GBZ and NE DRCs. In a second group of rats, the alpha 2-adrenoceptor antagonist, rauwolscine, was administered following base line DRCs to demonstrate rightward shifts of the NE and GBZ DRCs when PHE DRCs remained unaffected. Therefore, when boluses of NE are injected into the rat kidney, the vasoconstrictive responses are a result of the activation of both alpha 1- and alpha 2-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574956 TI - Colorimetric assay for cellular transglutaminase. AB - A colorimetric assay for cellular transglutaminase using 5 (biotinamido)pentylamine and polyvinylidine difluoride membranes for crude cellular preparations and purified enzyme has been developed. The biotinpentylamine substrate was incorporated into N,N-dimethylcasein by transglutaminase, the biotinylated products were adsorbed onto the membrane disks and conjugated with streptavidin-beta-galactosidase, and the absorbance resulting from the formation of p-nitrophenol from hydrolysis of p-nitrophenyl-beta-D galactopyranoside was measured at 405 nm. The validity of the assay was established by showing a good correlation, gamma = 0.922, between the colorimetric procedure and the commonly used radiometric filter paper method for the enzyme. The procedure offers a rapid, sensitive, and nonisotopic method for the estimation of cellular transglutaminase activity in as low as 20 ng of purified guinea pig liver transglutaminase and 10 micrograms of crude fibroblast cytosol protein. PMID- 2574957 TI - A microassay for the determination of soluble and membrane-bound glutamate decarboxylase activity--influences of cations, lipid composition, and pyridoxal 5'-phosphate on the glutamate decarboxylase binding to liposomes. AB - A radiochemical microassay for soluble and membrane-bound glutamate decarboxylase (GAD) is described. Up to 180 samples can be determined per day with a variation coefficient of 2%. The method detects newly synthesized gamma-amino-n-butyric acid in the picomole range and can easily be applied to other enzymes whose substrate and product differ by charge. In an aqueous homogenate of brain (1 + 10; w/v) about 15% of the total GAD activity are spun down by centrifugation (1 h, 100,000g) increasing to 35% of the total GAD activity in solutions with 8 mM calcium chloride or 100 mM potassium acetate. There is similar dependence on the cation concentration when GAD binds to phospholipid vesicles (liposomes) as well as dependence on lipid concentration and lipid composition. The coenzyme pyridoxal 5'-phosphate has no influence on GAD binding to liposomes. PMID- 2574958 TI - Distigmine and amitriptyline in the treatment of chronic pain. AB - Sixty-five patients attending a pain relief clinic were randomly allocated to treatment for 5 weeks with amitriptyline alone, distigmine alone, amitriptyline and distigmine started together, or addition of distigmine to preexisting treatment with amitriptyline. Forty-eight patients successfully completed the trial; the most common cause for withdrawal was dry mouth in the amitriptyline alone group. Two parameters were measured: Pain intensity was measured at the beginning and end of the treatment, and the saliva flow was measured at the beginning and the end of the treatment. At the end of 5 weeks, treatment with a combination of amitriptyline (75 mg/day) and distigmine (10 mg/day) resulted in a 43% reduction of pain and no subjectively noticeable mouth dryness. Distigmine alone also decreased pain and increased saliva flow, sometimes to the point of discomfort, whereas amitriptyline alone, in this particular series, did not significantly reduce pain and produced unpleasant mouth dryness. The addition of distigmine to preexisting (and ineffective) amitriptyline treatment failed to relieve pain. We therefore conclude that a combination of amitriptyline and distigmine (both given ab initio) may be a useful therapy for chronic pain. PMID- 2574959 TI - [Comparative postoperative course in coronary bypass: internal mammary versus saphenous vein after the first 6 postoperative hours]. PMID- 2574960 TI - [CD4 and CD8 lymphocyte populations after surgery in hip prosthesis]. PMID- 2574961 TI - [Curarization of the restitution of blood removed at the start of anesthesia for achieving normovolemic hemodilution]. PMID- 2574962 TI - [Monitoring of pH of the esophagus at the beginning of curarization with vecuronium]. PMID- 2574963 TI - [Effects of curarization of respiratory mechanics in anesthesia in patients with or without bronchopneumopathic obstruction]. PMID- 2574964 TI - [Comparison of the antagonistic effects of neostigmine and edrophonium on neuromuscular block induced by vecuronium in the diaphragm and thumb adductor]. PMID- 2574965 TI - [Effect of isoflurane concentration on the speed of decurarization of vecuronium after administration of neostigmine]. PMID- 2574966 TI - [Changes in heart rate after administration of neostigmine as a function of the morphinomimetic used]. PMID- 2574967 TI - [Interactions of cyclosporin with atracurium and vecuronium]. PMID- 2574968 TI - [Repercussions of esmolol given in the treatment of postoperative tachycardia on left ventricular function]. PMID- 2574969 TI - [Esmolol attenuation of hemodynamic changes in resuscitation of hypertensive and coronary patients]. PMID- 2574970 TI - [The effect of bolus esmolol on the cardiocirculatory response to endotracheal intubation]. PMID- 2574971 TI - Pulmonary neuroendocrine cells. Their secretory products and their potential roles in health and chronic lung disease in infancy. AB - Pulmonary neuroendocrine cells (PNEC) are granulated epithelial cells distributed throughout conducting airways. Among the bioactive products identified within the secretory granules of these cells are potent mitogens and bronchoactive and vasoactive agents. The secretory status of these cells, which are in greatest number in the fetus and newborn, is modulated by neural reflexes and by changes in airway gas composition. The aggregate data suggest roles for PNEC in airway "chemoception" and/or regulation of airway epithelial differentiation. Marked increases in PNEC are observed in bronchopulmonary dysplasia, where airway and alveolar fibrosis, epithelial metaplasia, and airway and vascular smooth muscle hypertrophy contribute to marked pathophysiologic changes in lung function. Considering the biologic effects of PNEC secretory products, particularly gastrin releasing peptide on airway epithelial cell and fibroblast proliferation, we propose that an increase in PNEC secretory products in the regenerating airway epithelium may contribute to the development of the pathologic alterations in lung structure seen in bronchopulmonary dysplasia. In this proposed scheme, secretion of abnormally large amounts of bronchoactive and vasoactive agents from PNEC (e.g., serotonin, gastrin-releasing peptide) in response to airway hypoxia and hypercapnia may be partially responsible in the genesis of reactive airway disease and pulmonary hypertension seen in this disease. PMID- 2574972 TI - [Primary sclerosing cholangitis. A report of 2 cases and review of the literature]. AB - Two cases are reported of primary sclerosing cholangitis (PSC) observed in the Institute of Gastroenterology of Sao Paulo-Brazil. These are presented together with a review of the relevant medical literature. Called our attention the delay for a definite diagnosis and the main symptoms that brought the patients to medical care. These were undoubtedly the progressive obstructive jaundice and severe pruritus. The role of the retrograde cholangio-pancreatography for definition of the diagnosis was presented. PMID- 2574974 TI - Zonation of fatty acid metabolism in rat liver. AB - Fatty acid metabolism was studied in periportal and perivenous hepatocytes isolated by the method of Chen & Katz [Biochem. J. (1988) 255, 99-104]. The rate of fatty acid synthesis and the activity of acetyl-CoA carboxylase were markedly enhanced in perivenous hepatocytes as compared with periportal cells. However, the response of these two parameters to short-term modulation by cellular effectors such as the hormones insulin and glucagon, the phorbol ester 4 beta phorbol 12 beta-myristate 13 alpha-acetate and the xenobiotics ethanol and acetaldehyde was similar in the two zones of the liver. In addition, perivenous hepatocytes showed a higher capacity of esterification of exogenous fatty acids into both cellular and very-low-density-lipoprotein lipids. Nevertheless, no difference between the two cell sub-populations seemed to exist in relation to the secretion of very-low-density lipoproteins. On the other hand, the rate of fatty acid oxidation was increased in periportal cells. This could be accounted for by a higher activity of carnitine palmitoyltransferase I and a lower sensitivity of this enzyme to inhibition by malonyl-CoA in the periportal zone. No differences were observed between periportal and perivenous hepatocytes in relation to the short-term response of fatty acid oxidation and carnitine palmitoyltransferase I activity to the cellular modulators mentioned above. In conclusion, our results show that: (i) lipogenesis is achieved at higher rates in the perivenous zone of the liver, whereas the fatty-acid-oxidative process occurs with a certain preference in the periportal area of this organ; (ii) the short term response of the different fatty-acid-metabolizing pathways to cellular effectors is quantitatively similar in the two zones of the liver. PMID- 2574973 TI - Neurotransmitter release from bradykinin-stimulated PC12 cells. Stimulation of cytosolic calcium and neurotransmitter release. AB - The effect of bradykinin on intracellular free Ca2+ and neurotransmitter secretion was investigated in the rat pheochromocytoma cell line PC12. Bradykinin was shown to induce a rapid, but transient, increase in intracellular free Ca2+ which could be separated into an intracellular Ca2+ release component and an extracellular Ca2+ influx component. The bradykinin-induced stimulation of intracellular free Ca2+ displayed a similar time course, concentration dependencies and extracellular Ca2+ dependence as that found for neurotransmitter release, indicating an association between intracellular free Ca2+ levels and neurotransmitter secretion. The selective BK1-receptor antagonist des Arg9,[Leu8]BK (where BK is bradykinin) did not significantly affect the stimulation of intracellular free Ca2+ or neurotransmitter release. In contrast, these effects of bradykinin were effectively blocked by the selective BK2 receptor antagonist [Thi5,8,D-Phe7]BK, and mimicked by the BK2 partial agonist [D Phe7]BK in a concentration-dependent manner. The stimulation of intracellular free Ca2+ and neurotransmitter release induced by bradykinin was shown not to involve voltage-sensitive Ca2+ channels, since calcium antagonists had no effect on either response at concentrations which effectively inhibit depolarization induced responses. These results indicate that bradykinin, acting through the interaction with the BK2 receptor, stimulates an increase in intracellular free Ca2+ leading to neurotransmitter secretion. Furthermore, bradykinin-induced responses involve the release of intracellular Ca2+ and the influx of extracellular Ca2+ that is not associated with the activation of voltage sensitive Ca2+ channels. PMID- 2574975 TI - Protein kinase C and dopamine release--III. Effect of dopamine depleting drugs. AB - The hypothesis that protein kinase C (PKC) may modulate the release of dopamine (DA) in the nigrostriatal pathway was supported by findings that injections of drugs which affect DA release in vivo result in changes in PKC activity in the striatum (Giambalvo CT, Biochem Pharmacol 37: 4009-4017, 1988). In the present study, it was found that the effects of the DA-acting drugs (apomorphine, LY 171555, SKF 38393, sulpiride, Sch 23390 and gamma-butyrolactone) on PKC activity were prevented by prior diminution of the endogenous stores of DA with alpha methyl-p-tyrosine (alpha-MT) or reserpine. This protective effect occurred at a dose and time when DA depletion was maximal, suggesting that the effects of the DA-acting drugs on PKC activity are dependent on the presence of an intact store of DA. Furthermore, since reserpine decreased the evoked release of DA, these results raise the possibility that PKC may be involved in the vesicular release process. Besides their effects on PKC activity, these depleting agents also prevented the DA-acting drugs from altering calmodulin-dependent protein kinase activity. PMID- 2574976 TI - Inhibitory action of carvedilol, a novel alpha, beta-adrenoceptor antagonist, on catecholamine secretion and calcium influx in cultured bovine adrenal chromaffin cells. AB - The effect of carvediolol on the secretory function was studied using cultured bovine adrenal chromaffin cells. Carvedilol caused the concentration-dependent inhibition of catecholamine secretion evoked by carbamylcholine, high K+ or veratridine. The drug also caused the inhibition of radioactive calcium uptake stimulated by these secretagogues into the cells, and the inhibition of calcium uptake was observed in parallel with that of catecholamine secretion. The inhibitory action of carvedilol on catecholamine secretion was shown to be similar to that caused by a classical beta-adrenoceptor antagonist, propranolol. Furthermore, although the level of carbamylcholine-stimulated catecholamine secretion inhibited by diltiazem, a potent calcium channel antagonist, was significantly raised by elevating the calcium concentration in the reaction mixture, increasing the concentration of calcium ions in the mixture failed to induce any substantial influence on the secretion inhibited by carvedilol, as well as propranolol, under the same experimental conditions. These results seem to indicate that carvedilol may cause the inhibition of catecholamine secretion through its blocking action on calcium influx into the cells, and suggest the possibility that the inhibitory action of carvedilol on calcium influx is presumably based on its stabilizing action on the plasma membranes rather than its blocking action on the calcium channels in the chromaffin cell. PMID- 2574977 TI - Inhibition of myointimal proliferation of the rat carotid artery by the peptides, angiopeptin and BIM 23034. AB - Proliferation of vascular smooth muscle is an early and major event in the formation of an atherosclerotic lesion. Here we report for the first time the inhibitory effects on myointimal proliferation of the rat carotid artery by a synthetic peptide, angiopeptin, and its closely related congener, BIM 23034. Proliferation was initiated in the carotid artery of anesthetized rats by air drying of the endothelium. After 15 days the rats were killed and the carotid artery was pressure-fixed and subjected to morphologic analysis for evaluation of the degree of myointimal thickening. Five synthetic somatostatin-like peptides were tested by pretreating rats (20 and 50 micrograms/kg/rat s.c. daily) for 2 days prior to and for 5 days after the endothelial injury. Angiopeptin and the closely related octapeptide (BIM 23034) significantly inhibited myointimal thickening. Angiopeptin was also effective when the pretreatment period was reduced from 2 days to 30 min. The inhibitory effect of angiopeptin was further confirmed in an additional experiment involving [3H]thymidine incorporation. In this experiment angiopeptin (100 micrograms/kg/day s.c.) was also administered for 2 days prior to and five days following the endothelial injury and it significantly inhibited thymidine uptake. All the peptides tested inhibit the release of growth hormone. However, only angiopeptin and BIM 23034 inhibited myointimal proliferation. Thus the effect of angiopeptin and its congener is unlikely to be mediated through growth hormone. Since angiopeptin inhibits myointimal proliferation it may have clinical utility in preventing restenosis following angioplasty and coronary artery by-pass procedures. PMID- 2574978 TI - The influence of N2-O2 and He-O2 saturation diving on electroencephalogram of human bodies. AB - This paper reports the changes of the EEG of human bodies during saturation exposure at different depths to different mixed gases. The results of the research show that the most obvious on EEG was the appearance of diffused slow waves, usually theta waves of 4-7 times/s, and delta waves of 2-3 times/s within individual subjects. The EEG changes at 50 m were more obvious than those at 36.5 m. With the prolonging of time under high pressure, the EEG had some improvements, for instance, the slow waves decreased and the alpha waves increased. There was a certain relationship between these changes and the symptoms which appeared in the human body. The chief factor of the EEG changes is due to the effect of nitrogen narcosis during the oxygen-nitrogen diving experiment. In addition, carbon dioxide retention under the high pressure is also a factor of the EEG changes, because repeated inhaling of CO2-dense mixtures could aggravate the EEG changes and the reduction of carbon dioxide in humans by hyperventilation could improve abnormal EEGs. The main changes of the EEG during the helium-oxygen exposure at 302 m were the increase of theta waves, and even of delta waves, the decrease in alpha rhythm and the decline of amplitude of alpha waves. Increased theta index and decreased alpha index could be seen at the depth of 302 m. Under any of the above-mentioned pressure conditions when slow waves characteristic of abnormal changes appeared in the EEGs, the EEGs could be temporarily improved by photic stimulation, i.e. slow waves disappeared and alpha waves reappeared. When photic stimulation was over, alpha waves disappeared and slow waves reappeared. It was indicated that abnormal changes of the EEG under high pressure were a kind of temporary and reversible changes of the brain function. PMID- 2574979 TI - [The hemodynamic and neurohumoral reactions induced by submaximal dynamic and isometric loading in hypertension patients]. AB - Changes in systemic hemodynamics and plasma catecholamine levels during and 4 min after the end of bicycle and isometric leg exercise were studied in 12 hypertensive patients. Dynamic exercise increased heart rate more and blood pressure less than isometric exercise; plasma norepinephrine (NE) level rose by 109%. Isometric exercise increased NE level only by 18%, but maximal changes (46%) occurred during recovery, probably reflecting a washout of NE from active muscles after the end of isometric contractions. It is concluded that during static exercise more pronounced pressor effect is associated with less activation of the sympathetic nervous system in comparison with dynamic exercise. PMID- 2574981 TI - "Don't bump my bed, don't touch my feet!". AB - The case history of a 14-year-old male pediatric oncology patient is presented to illustrate a complex problem in pain management. The patient had multifocal osteosarcoma and was treated with chemotherapy. Because his disease was never under control and always advancing, his pain was constantly changing. The numerous pathologies that caused his pain, its various characteristics, and the attempts made to alleviate it varied. Methods to assess and strategies to relieve pain, as well as the evaluation of pain relief interventions, are described.. PMID- 2574980 TI - Immunohistochemical evidence for different opioid systems in the rat superior cervical ganglion as revealed by imipramine treatment and receptor blockade. AB - The distribution pattern of opioid-immunoreactive nerve cell bodies and varicose fibres in the rat superior cervical ganglion after chronic administration of the tricyclic antidepressant imipramine, various receptor blockades (muscarinic antagonist, atropine sulphate; opiate antagonist, naloxone; kappa-antagonist, MR2266BS), and denervation was investigated immunohistochemically using a biotin streptavidin-peroxydase complex method. Antisera to four peptides derived from two different precursors of the opioid family were used. In control superior cervical ganglia sparsely scattered nerve fibres and no neuronal cell bodies were immunoreactive when antisera to dynorphin A (1-17) or alpha-neo-endorphin (cleavage products of prodynorphin) were applied. A moderate number of nerve fibres and neuronal perikarya were immunoreactive to antisera directed against met-enkephalin-arg-phe (cleavage product of proenkephalin) and leu-enkephalin (cleavage product of prodynorphin and proenkephalin); non-identical cell bodies contained met-enkephalin-arg-phe- or leu-enkephalin-immunoreactivity. After drug treatment specific changes in the immunoreactivity of the investigated peptides in the superior cervical ganglion were demonstrated. (a) Treatment with imipramine resulted in an increase of nerve fibres demonstrating immunoreactivity to antisera against dynorphin A and alpha-neoendorphin. In contrast, no alteration in the numbers of nerve fibers but a numerical increase of postganglionic cell bodies immunoreactive to either met-enkephalin-arg-phe or leu enkephalin antisera was demonstrated. Moreover, some perikarya exhibited immunoreactivity to both these opioids. (b) Receptor blockade with the muscarinic antagonist atropine sulphate or the general opiate antagonist naloxone had no effect on the number and distribution of dynorphin A or alpha-neoendorphin immunoreactive fibres, whereas both met-enkephalin-arg-phe and leu-enkephalin immunoreactive fibres and postganglionic perikarya were increased in number. (c) After the kappa antagonist (MR2266BS), an increase of fibres with prodynorphin derived opioid immunoreactivity as well as those with met-enkephalin-arg-phe- or leu-enkephalin-immunolabelling was visible and the met-enkephalin-arg-phe and leu enkephalin-immunoreactive cell bodies were increased in number. The preganglionic origin of the investigated fibres with prodynorphin cleavage products was concluded from the complete disappearance of such fibres after preganglionic denervation. Denervation also resulted in an increase of met-enkephalin-arg-phe- and leu-enkephalin-immunoreactive perikarya. Small intensely fluorescent (SIF) cells, which in controls were nonrea PMID- 2574982 TI - Family management programmes for schizophrenic patients. Prevention of relapse and modification of familial communication patterns. PMID- 2574983 TI - Dissemination of skills training modules to psychiatric facilities. Overcoming obstacles to the utilisation of a rehabilitation innovation. PMID- 2574984 TI - Treating prodromal episodes to prevent relapse in schizophrenia. PMID- 2574985 TI - [3-substituted 1,2-benzisoxazole and their neuroleptic activity]. AB - The authors report the synthesis of two new derivatives of 3-substituted 1,2 benzisoxazole. The new molecules (P-1368, P-1370), evaluated in many pharmacological C.N.S. tests, show interesting neuroleptic activity but inferior to those of haloperidol and chlorpromazine. PMID- 2574986 TI - Hormonal and metabolic responses to cholecystectomy: comparison of extradural somatostatin and diamorphine. AB - We have studied the metabolic and hormonal responses to surgery, and the pain scores and analgesic requirements in 24 patients undergoing cholecystectomy, allocated randomly to three groups to receive either general anaesthesia alone, or general anaesthesia with extradural diamorphine 0.1 mg kg-1, or general anaesthesia with extradural somatostatin to a total dose of somatostatin 3 mg. The only significant effect of extradural diamorphine was a decrease in the glucose response to surgery. Somatostatin 3 mg by the extradural route caused a significant increase in the concentration of circulating somatostatin which resulted in a significant decrease in plasma growth hormone and insulin after 60 min of surgery, together with an increase in plasma glycerol concentration. Patients in the diamorphine group required significantly less i.v. analgesia in the postoperative period than the other two groups. Intraoperative somatostatin failed to provide any postoperative analgesia. PMID- 2574987 TI - P-glycoprotein expression in treated and untreated human breast cancer. AB - The expression of P-glycoprotein in primary and recurrent human breast cancer was investigated by means of immunohistochemistry, using a monoclonal antibody (C219) and the streptavidin-biotin-peroxidase method. Twelve patients received no chemotherapeutic treatment. The other 11 patients were treated with chemotherapy, and all developed clinical resistance to it. No or only minimal reactivity was found in specimens coming from the untreated patients (12 cases) or from patients treated with substances not involved in the multidrug resistance phenomenon (four cases). In contrast, three out of seven tumours from patients treated with multidrug resistance related substances showed clear reactivity (positive staining in more than 20% of the tumour cells). In one of these cases, where specimens of the tumour could be studied before and after treatment, an association between the latter and expression of P-glycoprotein was suggested. Finally, this marked expression of P-glycoprotein only took place in tumours treated over a longer space of time (five courses or more of multidrug resistance related chemotherapy). PMID- 2574988 TI - In vitro evaluation of the potential of aclarubicin in the treatment of small cell carcinoma of the lung (SCCL). AB - The sensitivity of eight cell lines established from treated and untreated patients with small cell carcinoma of the lung (SCCL) was tested in the clonogenic assay with 1 h and continuous exposure to aclarubicin (ACLA), adriamycin (ADR), daunorubicin (DAU) and mitoxantrone (MITO). The sensitivity to ADR, DAU and MITO covariated, and varied with a factor of five. The sensitivity to ACLA was independent of the sensitivity to ADR and varied only within a factor of two. Only ACLA showed pronounced increased potency with continuous incubation, and ACLA was the most potent drug in the three cell lines least sensitive to ADR. Two resistant cell lines were selected by treating NCI-H69 in vitro with DAU. One cell line (9-fold resistant to DAU) expressed large amounts of P-glycoprotein, the other cell line (4-fold resistant to DAU) had barely detectable glycoprotein. Both lines acquired resistance to ADR, ACLA and MITO. The cross-resistance to ACLA and MITO was only partial and ACLA was still the most potent drug on these lines. The sensitivity to ACLA of the cell lines least sensitive to ADR suggest that ACLA partially circumvents mechanisms of multidrug resistance. Together with the pronounced increase in potency with prolonged exposure, these results suggest that ACLA has a mechanism of action different from the 'classical' anthracyclines. In this context mitoxantrone is more similar to the classical anthracyclines although its structure is more dissimilar. PMID- 2574989 TI - Restriction fragment length polymorphisms of L-myc and myb in human leukaemia and lymphoma in relation to age-selected controls. PMID- 2574990 TI - Identification of a new P450 expressed in human lung: complete cDNA sequence, cDNA-directed expression, and chromosome mapping. AB - A cDNA coding for a P450 expressed in human lung was isolated from a lambda gt11 library constructed from human lung mRNA using a cDNA probe to rat P450 IVA1. The cDNA-deduced amino acid sequence of this P450, designated IVB1, consisted of 511 amino acids and had a calculated molecular weight of 59,558. The IVB1 amino acid sequence bore 51%, 53%, and 52% similarities to rat IVA1, IVA2, and rabbit P450p 2, respectively. Comparison of the primary amino acid sequence of human IVB1 with rat IVA and rabbit p-2 P450 sequences revealed a region of absolute sequence identity of 17 amino acids between residues 304 and 320. However, the functional significance of this conserved sequence is unknown. Human IVB1 also appears to be related to P450 isozyme 5 that has been extensively characterized in rabbits. The IVB1 cDNA was inserted into a vaccinia virus expression vector and the enzyme expressed in human cell lines. The expressed enzyme had an absorption spectrum with a lambda max at 450 nm when reduced and complexed with carbon monoxide, typical of other cytochrome P450s. Unlike rabbit P450 isozyme 5, however, human IVB1 was unable to activate the promutagen 2-aminofluorene. Human lung microsomal P450s were also unable to metabolize this compound despite the presence of IVB1 mRNA in three out of four human lungs analyzed. In contrast to its expression in lung, IVB1 mRNA was undetectable in livers from 14 individuals, including those from which the lungs were derived. IVB1-related mRNA was also expressed in rat lung and was undetectable in untreated rat liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574991 TI - Molecular analysis of the murine C4b-binding protein gene. Chromosome assignment and partial gene organization. AB - Murine C4b-binding protein (C4BP) is a regulatory molecule in the classical pathway of complement. C4BP is composed predominantly of short consensus repeats (SCRs) approximately 60 amino acids in length, which contain a framework of conserved residues. The SCRs are found in many complement molecules and a growing number of noncomplement molecules as well and are a major structural feature of some of these molecules. To characterize the structure of the murine C4BP gene, a cosmid library constructed from Balb/c liver DNA was screened. Several nearly identical, overlapping clones were identified; however, none of the clones, alone or in combination, covered the entire C4BP gene. One clone (D26) was chosen for detailed analysis and found to contain all but the leader region, the first SCR, and the first half of the second SCR. The SCRs three through six were each encoded by single exons. Only the latter half of the second SCR was present on the clone, and it was encoded by a single exon, demonstrating that murine C4BP has a split SCR at the genomic level. Structural mapping of this portion of the gene demonstrates that the region extending from the second half of the second SCR through the nonrepeat and untranslated region spans approximately 12 kb; however, genomic Southern blot analysis suggests that the gene is between 20 and 30 kb in length. Analysis of the 3' genomic sequence demonstrates that this region of the gene has homology with SV-40 late (class II) RNA sequences. These sequences may play a role in 3' cleavage of the precursor RNA prior to polyadenylation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574992 TI - Diversity of oligosaccharide structures linked to asparagines of the scrapie prion protein. AB - Prion proteins from humans and rodents contain two consensus sites for asparagine linked glycosylation near their C-termini. The asparagine-linked oligosaccharides of the scrapie isoform of the hamster prion protein (PrP 27-30) were released quantitatively from the purified molecule by hydrazinolysis followed by N acetylation and NaB3H4 reduction. The radioactive oligosaccharides were fractionated into one neutral and three acidic oligosaccharide fractions by anion exchange column chromatography. All oligosaccharides in the acidic fractions could be converted to neutral oligosaccharides by sialidase digestion. Structural studies on these oligosaccharides including sequential exoglycosidase digestion in combination with methylation analysis revealed that PrP 27-30 contains a mixture of bi-, tri-, and tetraantennary complex-type sugar chains with Man alpha 1----6(GlcNAc beta 1----4)(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 (Fuc alpha 1----6)GlcNAc as their core. Variation is produced by the different combination of the oligosaccharides Gal beta 1----4GlcNAc beta 1----, Gal beta 1- --4(Fuc alpha 1----3)GlcNAc beta 1----, GlcNAc beta 1----, Sia alpha 2----3Gal beta 1----4GlcNAc beta 1----, and Sia alpha 2----6Gal beta 1----4GlcNAc beta 1--- in their outer chain moieties. When both asparagine-linked consensus sites are glycosylated, the diversity of oligosaccharide structures yields over 400 different forms of the scrapie prion protein. Whether these diverse asparagine linked oligosaccharides participate in scrapie prion infectivity or modify the function of the cellular prion protein remains to be established. PMID- 2574993 TI - Rapid kinetics of alpha 2-adrenergic inhibition of adenylate cyclase. Evidence for a distal rate-limiting step. AB - Activation and inhibition of adenylate cyclase in the presence of GTP, the natural guanine nucleotide regulator, are too fast to study by standard biochemical methods. In order to identify the rate-limiting steps in adenylate cyclase regulation, we measured the kinetics of stimulation and inhibition of the enzyme on a subsecond to second time scale using a novel rapid-mix quench technique. Even using our rapid-mix quench method, activation by PGE1 and forskolin was instantaneous (cAMP accumulation was linear between 0.5 and 30 s). In contrast, we found a lag period of 1.2-10 s for epinephrine-mediated inhibition. The length of the lag depended on the concentration of GTP and monovalent cations present. In the absence of NaCl, the rate constant for the onset of inhibition (kinh) increased only slightly with GTP concentration saturating at a value of 0.16 s-1 (t1/2 4.3 s) at 1 microM GTP. In the presence of 100 mM NaCl, kinh was strongly dependent on GTP concentration, reaching a maximum value of 0.57 s-1 (t1/2 1.2 s) at 100 microM GTP. Thus, activation of both Gi and Gs in intact platelet membranes is much faster (t1/2 less than 5 s) than previously reported for reconstituted systems. Also, the strong dependence of the rate of adenylate cyclase inhibition on GTP concentration implies that the rate-limiting step in inhibition is distal to GTP binding. The effect of NaCl to increase the maximal rate of inhibition is specific for sodium since KCl has no effect on kinh.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2574994 TI - Characterization of a transport system for anionic amino acids in human fibroblast lysosomes. AB - L-Aspartate and L-glutamate are transported into human fibroblast lysosomes by a single, low Km, Na(+)-independent transport system, which has been provisionally named lysosomal system d. This system resembles the Na(+)-dependent plasma membrane system chi-AG, although these differences have been observed: (1) lysosomal system d recognizes the D- as well as the L-isomers of both aspartate and glutamate, whereas only for aspartate is the D-isomer recognized by system chi-AG; (2) the anion L-homocysteate is not accepted by system chi-AG, but is an effective inhibitor of lysosomal system d; (3) N-methyl, alpha-methyl, and omega hydroxamate derivatives of both aspartate and glutamate inhibit lysosomal system d, but only the aspartate derivatives are accepted by system chi-AG; (4) lysosomal system d shows a preference for the substrate amino group in the alpha position, a preference not seen for system chi-AG. These points imply differences at the two recognition sites with respect to substrate length, size, and rotation, with the lysosomal site generally being the less restrictive. PMID- 2574995 TI - Adenosine, a cytoprotective autocoid: effects of adenosine on neutrophil plasma membrane viscosity and chemoattractant receptor display. AB - At inflammatory sites neutrophils are stimulated to produce a variety of toxic agents, yet rarely harm the endothelium across which they migrate. We have recently found that endothelium releases adenosine which, acting via receptors on the surface of human neutrophils, inhibits generation of toxic metabolites by stimulated neutrophils but, paradoxically, promotes chemotaxis. Agents which diminish plasma membrane viscosity affect neutrophil function similarly, possibly by modulating chemoattractant receptor number or affinity. We therefore determined whether adenosine receptor agonists modulate neutrophil function by decreasing membrane viscosity and/or changing the affinity of chemoattractant (N fMet-Leu-Phe, FMLP) receptors. Surprisingly, 5'-(N-ethylcarboxamido)adenosine (NECA, 10 microM), the most potent agonist at neutrophil adenosine receptors, increased plasma membrane viscosity, as measured by fluorescence anisotropy of the plasma membrane specific probe 1-(4-trimethylaminophenyl)-6-diphenyl-1,3,5 hexatriene (TMA-DPH), in unstimulated neutrophils from a mean microviscosity of 1.67 +/- 0.02 (S.E.) to 1.80 +/- 0.02 (p less than 0.001) while inosine (10 microM), a poor adenosine receptor agonist, had no effect (1.73 +/- 0.04, p = n.s. vs. control, p less than 0.01 vs. NECA). Adenosine receptor agonists increased plasma membrane viscosity in neutrophils with the same order of potency previously seen for inhibition of superoxide anion generation and enhancement of chemotaxis (NECA greater than adenosine = N6-phenylisopropyladenosine). The adenosine receptor antagonist 8-(p-sulfophenyl)theophylline reversed the effect of NECA on plasma membrane viscosity. Unlike other agents which modulate plasma membrane viscosity, NECA (10 microM) did not significantly change the number or affinity of [3H]FMLP binding sites on neutrophils. In contrast to the hypothesis of Yuli et al. these results indicate that occupancy of adenosine receptors on neutrophils increases plasma membrane viscosity without affecting chemoattractant receptor display. PMID- 2574996 TI - Binding of a radiolabeled sea anemone cytolysin to erythrocyte membranes. AB - Stichodactyla helianthus cytolysin III, a 17 kDa basic polypeptide isolated from a Caribbean sea anemone, is one of the most potent hemolysins yet found in a living organism. This toxin has been reported to form new ion channels in artificial lipid bilayer membranes. The ability of this toxin to attack cell membranes is greatly enhanced by the presence of sphingomyelin. In order to investigate the mechanism by which the cytolysin causes cell lysis, we have prepared a highly active [3H]cytolysin derivative by reductive methylation with sodium cyanoborohydride and [3H]formaldehyde. A dimethylated toxin derivative was used to investigate the basis for the differential lytic activity of this polypeptide upon erythrocytes from six mammalian species. Using both direct [3H]toxin binding and indirect (Thron method) binding techniques, we found that the interspecies differences are due to variable membrane susceptibilities toward the bound toxin, rather than to differences in membrane affinity for the toxin. Similarly, we showed the enhanced lytic activity of the toxin for rat erythrocytes at elevated pH to be caused by enhanced activity of the bound toxin. PMID- 2574997 TI - Hydrostatic pressure studies of native and synthetic thick filaments: in vitro myosin aggregates at pH 7.0 with and without C-protein. AB - Column-purified myosin at pH 7.0 will reproducibly aggregate into filaments of known average length and structure when dialyzed against a low ionic strength medium under controlled conditions. When exposed to increased hydrostatic pressure, followed by quick return to atmospheric pressure, the original filaments shorten linearly with increasing pressure; in addition, a second population of filaments is seen, presumably the result of reaggregation of myosin after release of pressure. This second population is about 0.5 microns long, bipolar, and about half the diameter of the original filaments. The number of these filaments, but not their physical characteristics, is a function of the shortening of the original filament population. Both the remnants of the original population and the new aggregates, once formed, are stable over time and at room temperature. The addition of C-protein to myosin solutions before filament preparation results in a filament population of slightly shorter length. When these filaments are exposed to increased hydrostatic pressure, they are more resistant to disaggregation than myosin filaments without C-protein. However, like the filaments prepared in the absence of C-protein, a second population of shorter, thinner filaments is visible after exposure to pressure. PMID- 2574998 TI - [The mechanism of action of a synthetic derivative of 1,4-naphthoquinone on the respiratory chain of liver and heart mitochondria]. AB - It was found that the 1.4-naphthoquinone derivative AK-135 (2-methyl-3-piperidine methyl-1.4-naphthoquinone hydrochloride) possesses a marked acceptor capacity during succinate and glutamate oxidation by rat liver and rabbit heart mitochondria. AK-135 fully restores the rate of glutamate (but not succinate) oxidation by liver and heart mitochondria catalyzed by rotenone, antimycin A and cyanide. In non-phosphorylating preparations of liver and heart mitochondria, AK 135 eliminates the inhibition of respiration on exogenous NADH induced by the same electron transport inhibitors. In liver mitochondria, the stimulation of succinate oxidation is due to a reverse electron transfer, whereas in the heart it proceeds via the rotenone-insensitive pathway. The experimental results suggest that in the liver and heart AK-135 accepts electrons from NADH dehydrogenase oxidizing endogenous NADH. Besides, in the liver this compound is also capable of accepting electrons from NADH-cytochrome b5 reductase. PMID- 2574999 TI - Temperature-induced changes in the coenzyme environment of D-amino acid oxidase revealed by the multiple decays of FAD fluorescence. AB - A temperature-dependent change in the microenvironment of the coenzyme, FAD, of D amino acid oxidase was investigated by means of steady-state and picosecond time resolved fluorescence spectroscopy. Relative emission quantum yields from FAD bound to D-amino acid oxidase revealed the temperature transition when concentration of the enzyme was lowered. The observed fluorescence decay curves were well described with four-exponential decay functions. The amplitude of the shortest lifetime (tau 0), approximately 25 ps, was always negative, which indicates that the fluorescence of D-amino acid oxidase at approximately 520 nm appears after a metastable state of the excited isoalloxazine decays. The other components with positive amplitudes were assigned to dimer or associated forms of the enzyme, monomer, and free FAD dissociated from the enzyme. Ethalpy and entropy changes of intermediate states in the quenching processes were evaluated according to the absolute rate theory. The temperature transition was much more pronounced in the monomer than in the dimer or associated forms of the enzyme. PMID- 2575001 TI - Benzodiazepine research: current findings and practical consequences. AB - The recent research literature on the effects of benzodiazepines is reviewed, with special emphasis on findings relevant for the practising clinician. The mode of action, patterns of use and abuse potential of benzodiazepines are discussed. The evidence on the risks of dependency and possible drawbacks of long-term use are examined. The possible effects of benzodiazepine use on psychological treatments are also examined, and factors that should be considered while treating benzodiazepine users are discussed. PMID- 2575000 TI - Genomic DNA analysis of the estrogen receptor gene in breast cancer. AB - A human estrogen receptor (ER) cDNA probe was used to examine genomic DNA extracted from 59 primary invasive breast cancers. The tumors were also studied histopathologically, and their ER status was assessed by hormone-binding assay and immunohistochemical analysis. Southern blots of genomic DNA samples digested with restriction endonucleases (BamHI, EcoRI, HindIII, PvuII, XbaI) revealed identical restriction fragments for each tumor, indicating preservation of gross ER gene integrity regardless of ER status, clinical stage, or histopathologic appearance. Digestion with PvuII identified a single, two-allele polymorphism with band(s) at 1.6 and/or 0.7 kb. The homozygous 1.6 kb pattern was present in 14 (24%) patients, the heterozygous 1.6/0.7 kb pattern in 29 (49%) patients and the homozygous 0.7 kb pattern in 16 (27%) patients. The PvuII restriction fragment length polymorphism (RFLP) within the ER gene showed no correlation with the results of the ER binding assay, the immunohistochemical analysis, clinical stage, or histopathologic appearance. A significant correlation was found between the genotypes and patient age at the time of tumor diagnosis. Tumors with the homozygous 1.6 kb and the heterozygous 1.6/0.7 kb patterns were observed in older women with mean ages of 64.6 and 64.4 years, respectively. In contrast, patients with tumors containing the homozygous 0.7 kb pattern were significantly younger, with a mean age of 50.4 years (p-value = 0.0024). The mechanism by which the homozygous 0.7 kb genotype is associated with breast cancer in the premenopausal age group is unknown. PMID- 2575002 TI - Transient recurrence of auditory hallucinations during acute dystonia. AB - Three schizophrenic patients who had transient recurrence of auditory hallucinations during acute dystonia precipitated by neuroleptic medication are reported. If it is accepted that psychotic symptoms result from dopaminergic overactivity, such phenomena suggest that acute dystonia might also have been caused by increased dopaminergic neurotransmission in these cases. PMID- 2575003 TI - Tardive dyskinesia in bipolar affective disorder: relationship to lithium therapy. AB - Forty patients under the age of 60 years with a DSM-III diagnosis of bipolar affective disorder were examined for the presence of tardive dyskinesia. The overall prevalence was 22.5%, with an age-related increase. Patients with and without tardive dyskinesia did not differ in terms of duration of affective illness or exposure to neuroleptics, but those patients with tardive dyskinesia had significantly more psychiatric admissions and were on lithium for significantly greater lengths of time. PMID- 2575004 TI - Antibodies directed against tyrosine hydroxylase differentially recognize noradrenergic axons in monkey neocortex. AB - In previous immunohistochemical studies of monkey neocortex, we found that antisera directed against tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) appeared to label distinct populations of neocortical axons, which presumably were dopaminergic and noradrenergic, respectively. In the present study, we further evaluated the apparent selectivity of this rabbit anti-TH antiserum for cortical dopaminergic fibers in monkeys by comparing it with two other anti-TH antibodies, a mouse monoclonal and a sheep polyclonal. In addition, the latter two anti-TH antibodies were used in double-labeling studies with a rabbit anti-DBH antiserum. In both single- and dual-label studies, each anti-TH antibody visualized a similar population of cortical axons, although the number of labeled fibers differed across antibodies. That is, in some cortical regions and layers, both the sheep and mouse anti-TH antibodies labeled more cortical fibers than did the rabbit anti-TH antiserum. Thus, the former two antibodies appeared to identify a subpopulation of TH-containing fibers that the latter antibody did not. Dual-label experiments, involving the rabbit anti-DBH antiserum and either the sheep or mouse anti-TH antibodies, demonstrated numerous neocortical DBH-immunoreactive axons in which TH was not detectable immunohistochemically. The percentage of DBH-immunoreactive fibers that were single-labeled differed across cortical regions and with the anti-TH antibody employed. For example, in primary motor cortex the mouse anti-TH antibody did not label 99.4% of the DBH-positive fibers, whereas in primary visual cortex, 76.4% of the DBH-immunoreactive axons were identified by the sheep anti-TH antibody. The results of these studies indicate that many DBH-immunoreactive, presumably noradrenergic, axons in monkey neocortex are not visualized by anti-TH antibodies, and that the ability of anti-TH antibodies to identify noradrenergic cortical axons in monkeys differs substantially among anti-TH antibodies and across cortical regions. These findings may be consistent with previous reports suggesting that the TH molecule is present in different concentrations or molecular forms in dopaminergic and noradrenergic cortical fibers. Finally, this study demonstrates that the labeling characteristics of a particular anti-TH antibody must be carefully evaluated, particularly in studies of primate neocortex, in order to properly interpret the results of those studies. PMID- 2575005 TI - Effects of glucose deficiency on glutamate/aspartate release and excitatory synaptic responses in the hippocampal CA1 area in vitro. AB - The effects of glucose deficiency on (1) the K+-evoked release of glutamate and aspartate and (2) excitatory synaptic transmission were studied in the Schaffer collateral-commissural-ipsilateral associational (SCCIA) projection to area CA1 of the rat hippocampal formation in vitro. Compared with 1 or 10 mM glucose, superfusion of CA1 slices with 0.1 mM glucose enhanced the K+-evoked release of both glutamate and aspartate, increased the ratio of aspartate release to glutamate release and did not affect the release of GABA. With both high and low glucose concentrations, the K+-evoked release of glutamate and aspartate originated predominantly from a Ca2+-sensitive store associated with the SCCIA projection. Superfusion with glucose-deficient medium abolished the inhibitory effect of adenosine on glutamate and aspartate release, but augmented the enhancing effect of the adenosine antagonist 8-phenyltheophylline. These results suggest that enough endogenous adenosine was released from the slices under these conditions to saturate the presynaptic A1 receptors. Despite its facilitatory effect on excitatory transmitter release, glucose-deficient medium inhibited transmission at Schaffer collateral-commissural synapses. Even when the postsynaptic response to a single electrical pulse was abolished, however, a substantial response could still be evoked through paired-pulse or frequency potentiation and the inhibition promptly reversed upon superfusion with 10 mM glucose. The increased ratio of aspartate release to glutamate release appears to reflect changes in the tissue content of these amino acids. The enhanced release of both excitants is suggested to result partly from a rise in intraterminal Ca2+ concentration and partly from inhibition of glutamate/aspartate uptake. Enhanced aspartate release may be particularly relevant to hypoglycemic damage in the CA1 area, because aspartate is a more potent hippocampal excitotoxin than glutamate. PMID- 2575006 TI - Coexistence of somatostatin with neuropeptide Y, but not with cholecystokinin or vasoactive intestinal peptide, in neurons of the rat amygdala. AB - A two-color immunoperoxidase procedure was used to determine whether somatostatin (SOM) containing neurons in the amygdala also contain neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), or cholecystokinin (CCK). There was no evidence that SOM-containing neurons in any of the amygdaloid nuclei contain VIP or CCK. In contrast, there was extensive colocalization of SOM and NPY in all of the amygdaloid nuclei with the exception of the intercalated masses and the lateral subdivision of the central nucleus. The greatest number of SOM-NPY double labeled cells was observed in the medial nucleus, lateral nucleus, and intra amygdaloid portion of the bed nucleus of the stria terminalis. The morphology of these SOM-NPY neurons was similar in all nuclei. Most exhibited fusiform or ovoid cell bodies with one or two sparsely branched dendrites emerging from each pole of the cell. The extensive coexistence of SOM and NPY in non-pyramidal neurons of the basolateral amygdala is similar to that seen in the cerebral cortex and supports the concept that these brain regions share many important characteristics. The extensive colocalization of SOM and NPY in the medial amygdala, in conjunction with the results of previous studies, suggests that some of these cells may project to the bed nucleus of the stria terminalis and hypothalamus. PMID- 2575007 TI - Ultrastructural localization of choline acetyltransferase in the rat rostral ventrolateral medulla: evidence for major synaptic relations with non catecholaminergic neurons. AB - Pharmacological and biochemical studies suggest that interactions between cholinergic and catecholaminergic and catecholaminergic neurons, particularly those of the C1 adrenergic cell group, in the rostral ventrolateral medulla (RVL) may be important in cardiovascular control. Ultrastructural localization of choline acetyltransferase (ChAT), the biosynthetic enzyme for acetylcholine, and its relation to neurons exhibiting immunoreactivity for catecholamine- (tyrosine hydroxylase; TH) or adrenaline (phenylethanolamine-N-methyltransferase; PNMT) synthesizing enzymes were examined in the RVL using dual immunoautoradiographic and peroxidase anti-peroxidase (PAP) labeling methods. By light microscopy, the ChAT-immunoreactive neurons were located both dorsally (i.e. the nucleus ambiguus) and ventromedially to those labeled with TH or PNMT (TH/PNMT). A few ChAT-labeled processes were dispersed among TH/PNMT-containing neurons with the majority of overlap immediately ventral to the nucleus ambiguus. By electron microscopy, ChAT-immunoreactivity (ChAT-I) was detected in neuronal perikarya, dendrites, axons and axon terminals and in the vascular endothelial cells of certain blood vessels. The ChAT-labeled perikarya in the ventromedial RVL were medium-sized (15-20 microns), elongated, contained abundant cytoplasm and had had slightly indented nuclei. Synaptic junctions on ChAT-immunoreactive perikarya and dendrites were primarily symmetric with 64% (45 out of 70) of the presynaptic terminals unlabeled. The remaining terminals were immunoreactive for ChAT (30%) or TH/PNMT (6%). Terminals with ChAT-I were large (0.8-2.0 microns) and contained numerous small clear vesicles and 1-2 dense core vesicles. Seventy-seven percent (112 out of 145) of the ChAT-labeled terminals formed symmetric synapses with unlabeled perikarya and dendrites, whereas only 8% were with TH/PNMT-labeled perikarya and dendrites, and 15% were with ChAT-immunoreactive perikarya and dendrites. We conclude (1) that cholinergic neurons in the RVL principally terminate on and receive input from non-catecholaminergic neurons, and (2) that the reported sympathetic activation following application of cholinergic agents to the RVL may be mediated by cholinergic inhibition of local inhibitory interneurons. The observed synapses between ChAT and TH/PNMT-containing neurons suggests that cholinergic and adrenergic neurons additionally may exert a minor reciprocal control on each other and thus may modulate their response to the more abundant input from afferents containing other transmitters. PMID- 2575008 TI - Cardiovascular changes induced by the local application of glutamate-related drugs in the rat nucleus tractus solitarii. AB - The effects of the local application of drugs acting on glutamatergic receptors in the nucleus tractus solitarii (NTS) were investigated in anesthetized rats. Unilateral microinjection of agonists (L-glutamate, L-aspartate, N-methyl-D aspartate (NMDA) and quisqualate) produced a dose-dependent hypotension and bradycardia. The effects of NMDA were prevented by low doses of the selective NMDA-receptor antagonist, 2-amino-5-phosphonovalerate (2-APV), or by the mixed NMDA/kainate antagonist, gamma-D-glutamylglycine. The response to all agonists and the bradycardia which was elicited in response to the intravenous administration of phenylephrine (vagal reflex response) could be prevented by the local microinjection of the glutamate antagonists kynurenic acid (3 nmol) and 2 APV (10 nmol) into the NTS. The present data suggest that in the NTS, NMDA and quisqualate receptors are implicated in blood pressure reflex regulation. PMID- 2575009 TI - Adrenergic innervation of the substantia innominata: co-localization of phenylethanolamine N-methyltransferase and tyrosine hydroxylase immunoreactivities within the same axons. AB - Adrenergic input to the rat substantia innominata (SI) was studied by immunocytochemical localization of phenylethanolamine N-methyltransferase (PNMT), the synthetic enzyme for adrenaline. Using primary antibodies derived from different species, we demonstrated in double-immunofluorescence labeling experiments that all PNMT-immunoreactive fibers in SI are also immunoreactive for tyrosine hydroxylase, the synthetic enzyme for dopamine. This result indicates that the PNMT immunoreactive axons in SI are indeed adrenergic fibers. PMID- 2575010 TI - [Method of isolating FMRF-amide-like substances in the snail, using affinity chromatography coupled with HPLC]. AB - An extraction procedure of FMRFa-like substances from brain of Helix aspersa was developed. It consists of using affinity chromatography coupled with reverse phase HPLC. Three synthetic peptides (FMRFa, pQDPFLRFa, Met-enkephalin) were used to evaluate the specificity and yield of the affinity column. Its efficiency was tested by use of snail brain extracts. The results showed that this method is efficient and reproducible. PMID- 2575012 TI - [The use of flumazenil at a pediatric surgical resuscitation unit]. PMID- 2575011 TI - [Prolonged fasting on the lipolytic activity of isolated adipocytes of the rat epididymis]. AB - Male Wistar rats, 6-8 week old, were fasted for 72 hours. The in vitro lipolytic activity of epididymal adipocytes was measured in the presence of adrenalin (a alpha and beta adrenergic agonist), isoprenaline (a pure beta agonist), theophylline (a phosphodiesterase inhibitor) or UK 14304 (a alpha 2 adrenoceptor agonist) associated with adenosine deaminase. The basal lipolytic activity, expressed per 100 mg lipids, was higher in fasted adipocytes than in fed ones. Its stimulation by adrenalin or isoproterenol was decreased by fast. The effects of these drugs were more potentiated by theophylline in fasted adipocytes than in fed ones. The UK 14304 inhibition of adenosine deaminase-stimulated lipolysis was about 20% in fasted adipocytes and 50% in fed adipocytes. The in vitro resistance of fasted adipocytes to the lipolytic effect of adrenalin or isoproterenol may be related to the hypothyroid status of fasted rats. PMID- 2575013 TI - Vasovagal syncope: management with atrioventricular sequential pacing and beta blockade. AB - A case of vasovagal syncope in an otherwise healthy 74-year-old woman is described. Attempts to prevent symptoms with ventricular and atrioventricular sequential temporary pacing (documented by continuous monitoring of heart rate and intra-arterial recording of blood pressure during spontaneous episodes) proved inadequate. However, the addition of a beta-blocker to permanent DDD pacing was clinically successful in markedly diminishing symptoms. The mechanisms of action of this treatment modality is discussed. PMID- 2575014 TI - CV 205-502: safety, tolerance to, and efficacy of increasing doses in patients with Parkinson's disease in a double-blind, placebo crossover study. AB - CV 205-502 (CV) is a long-acting dopamine agonist with potent D2 and weak D1 activity, which has not as yet been tested in patients with Parkinson's disease. We performed a dosage ranging and placebo crossover study in six patients to evaluate the efficacy and tolerance of CV when used as an adjunct to Sinemet in patients with Parkinson's disease. All patients had striking improvement. This effect was lost with placebo substitution and regained with reintroduction of CV. Benefits were sustained throughout the 6 month study. Single daily dosing could sustain the response in all but one patient. Adverse effects were mild and transient and resolved with dosage manipulation or a divided dosage regimen. CV is a promising drug for use in Parkinson's disease and further studies are indicated to test its long-term safety and efficacy. PMID- 2575015 TI - [Comparison of tolerance to hydrophilic contact lenses made of Hema (37% H2O) and Hema-Degma (55%, 65% H2O) in the rabbit eye. I. Changes in corneal transparency due to disturbed hydration]. AB - The authors compared on the rabbit eye the tolerance of hydrophilic contact lenses with equal parameters (0.2 mm central and peripheral thickness, 7.4 radius, 15 mm diameter) with a different degree of hydration (37% H2O-Hema), (55% and 65% H2O-Hema-Degma) during continuous wear for a period of two weeks (1, 2, 3, 4, 7 and 14 days). Special attention was devoted to changes in the transparency of the cornea. Changes of the transparency due to wearing of contact lenses were due to changes of corneal hydration. The cause of increased corneal hydration were metabolic and later also morphological disorders in the corneal endothelium. The activity of Na+-K+-dependent adenosine triphosphatase and gamma glutamyl transferase were reduced, followed by a change in the shape and size of endothelial cells. Later the activities of both enzymes were reduced also in the epithelium. Keratocytes had reduced alkaline phosphatase and gamma-glutamyl transferase activities. The staining properties of glycosaminoglycans in the stroma remained, however, unaltered, similarly as the activity of acid glycosidases and other investigated lysosomal enzymes. The onset of increased corneal hydration caused by a disorder of the active water ion transport and of metabolites in the cornea depended on the percentage of water in hydrophilic contact lenses. It was observed latest after application of contact lenses with 65% water. PMID- 2575016 TI - Inhibitory effect of a lichen polysaccharide sulfate, GE-3-S, on the replication of human immunodeficiency virus (HIV) in vitro. AB - A sulfate (GE-3-S) prepared by chlorosulfonic acid treatment of GE-3, a partially acetylated beta(1----6) glucan of the lichen Umbilicaria esculenta, inhibited the cytopathic effect of human immunodeficiency virus (HIV) and suppressed the HIV antigen expression in Molt-4 (clone 8) cells. GE-3-S also suppressed the giant cell formation of HIV-infected Molt-4 cells, and inhibited HIV-induced plaque formation by 50% at the dose of 19.5 micrograms/ml and completely at 250 micrograms/ml in MT4 cells. GE-3-S had no direct effect on the reverse transcriptase of HIV. PMID- 2575017 TI - Evaluation of TSH receptor antibody by 'natural in vivo human assay' in neonates born to mothers with Graves' disease. AB - Neonatal thyrotoxicosis induced by transferred TSH receptor antibody (TRAb) is the ideal human in-vivo experimental system for the evaluation of TRAb. The clinical significance of circulating TRAb in Graves' disease was evaluated by this 'natural in-vivo human assay'. TRAb activity in vitro was measured by radioreceptor assay (thyrotrophin-binding inhibitor immunoglobulin, TBII) and sensitive cAMP accumulation assay using FRTL-5 cells (thyroid-stimulating antibody, TSAb). Further, the binding-stimulation index (B-S index) was newly introduced, which was the most useful indicator for prediction of neonatal thyrotoxicosis, calculated as the product of TBII and TSAb (Tamaki et al., 1988a). Maternal serum TRAb indices showed highly significant correlations with the serum free T4 index (FT4I) and free T3 index (FT3I) in neonates (5-10 days after birth) born to 20 mothers with Graves' disease who had positive TBII and/or TSAb (FT4I: r = 0.825 for TBII, r = 0.908 for TSAb, r = 0.944 for the B-S index, P less than 0.001; FT3I: r = 0.622 for TBII, P less than 0.01, r = 0.812 for TSAb, r = 0.791 for the B-S index, P less than 0.001; n = 20). In contrast, in 57 untreated adult patients with hyperthyroid Graves' disease, the FT4I and FT3I levels were not correlated with any of the TRAb indices. The linear regression relationship between the B-S index and FT4I found in neonates was applied to values in adult patients with Graves' disease, and the patients were divided into three groups on the basis of the 95% confidence limit: high, normal, and low responders of thyroid hormone (FT4I) secretion to the B-S index. FT4I and the ratio of FT4I to the B-S index were highest and the TRAb indices were lowest in the high responders, while FT4I and the FT4I/B-S index ratio were lowest and the TRAb indices were highest in the low responders. The FT4I/B-S index ratio was inversely correlated with the titres of antithyroid microsomal antibody in all the adult patients with untreated Graves' disease (r = -0.288, P less than 0.05). The results suggest that in-vitro assays using animal thyroid cells and cAMP as an index of response are suitable for detecting circulating thyroid stimulating activity in vivo. Secretion of thyroid hormones in Graves' disease may be regulated not only by circulating thyroid-stimulating antibodies but also by intrathyroidal stimulatory factors or by inhibitory or destructive factors. PMID- 2575018 TI - The long-term outcome of thyroidectomy for sporadic non-toxic goitre. AB - To study the long-term outcome after thyroidectomy, 113 sporadic non-toxic goitre patients who underwent thyroidectomy in our hospital in the period 1974-1983, were studied. Five patients complained of recurrent goitre; a goitre was found on inspection and palpation in these five and in 15 others. There were no differences between the 20 patients with goitre and the 93 patients without goitre with regard to sex, age, duration of goitre, indication and type of thyroidectomy, postoperative thyroid hormone medication, period of follow-up, and T4, T3, or TSH plasma values at the time of follow-up examination. Twenty-three patients complained of voice changes since thyroidectomy. In a case control study, included in this follow-up study, 19 patients with goitre, i.e. thyroid size I and II as estimated by inspection and palpation (cases), and 16 patients without goitre, i.e. thyroid size OA and OB (controls), were studied in more detail. No difference between cases and controls was found in any of the above mentioned parameters that could explain the recurrence of goitre. Thyroid volume (median) was greater in the cases (34.1 ml, range 7.9-83.4) than in the controls (10.3 ml, range 2.5-48.7) (P less than 0.001), although a considerable overlap between the two groups was observed. One or more thyroid nodules were found in 89.5% of the cases and in 62.5% of the controls (NS). Serum thyroid growth stimulating immunoglobulin (TGI) was present both in cases (68%) and controls (50%). TGI was present in high titres in all five patients who complained about recurrent goitre.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575019 TI - Management of acute non-Q-wave myocardial infarction: role of prophylactic pharmacotherapy and indications for predischarge coronary arteriography. AB - Non-Q-wave myocardial infarction (MI) differs from Q-wave MI in three important respects: (1) smaller infarct size possibly due to early reperfusion as a result of spontaneous thrombolysis, relief of spasm, or both; (2) more frequent patency of the infarct-related artery; and (3) a larger residual mass of viable but jeopardized myocardium within the perfusion zone of the infarct-related vessel. Left ventricular function, unless impaired by previous MI, is generally better. The prognosis is worse after the acute phase, when residual ischemia is present, and reinfarction rates during hospitalization and in the subsequent year of follow-up are higher. Obviously, since myocardial ischemia is potentially reversible, its presence should be energetically sought in all patients with recognized non-Q-wave MI. Based on our current understanding and available data, the following guidelines for the management of non-Q-wave MI patients can be recommended: (1) antiplatelet therapy along with diltiazem should be administered to patients as soon as the diagnosis is established, unless contraindications exist; (2) patients who develop early recurrent ischemia on therapy, that is, angina with associated ST-T-wave changes, should undergo prompt cardiac catheterization and myocardial revascularization; (3) patients with entirely uncomplicated hospital courses who are asymptomatic should undergo exercise stress testing, preferably in conjunction with thallium-201 imaging, before hospital discharge. Only those with evidence of significant residual ischemia need cardiac catheterization and myocardial revascularization. PMID- 2575020 TI - Strategies for managing the patient with acute non-Q-wave myocardial infarction. AB - The prognosis for patients with non-Q-wave myocardial infarction (MI) remains controversial, although a number of studies have shown a less favorable outlook after hospital discharge for patients with non-Q-wave than for those with Q-wave infarction. Numerous management strategies are available to the clinician, many of which involve an interventional strategy (myocardial revascularization with coronary bypass surgery or angioplasty) or a more conservative approach which emphasizes secondary prevention with medical therapy. This review summarizes the role of identifying risk variables in patients with non-Q-wave MI and their importance to clinical decision making. Based on data obtained from the Diltiazem Reinfarction Study (DRS), it has been shown that 20% of patients experience one or more episodes of spontaneous postinfarction angina which is associated with a significant increased (33%) 2-week mortality and an appreciable fivefold increased incidence of early reinfarction compared to patients without early recurrent ischemia. Similar findings have been observed in this same cohort of patients who were followed for one year, in that there was twofold higher incidence of death and late reinfarction at one year of follow-up. Other risk factors also appear to be important determinants of adverse long-term outcome after non-Q-wave MI and include persistent ST segment depression on serial electrocardiograms, congestive heart failure, and left ventricular hypertrophy. Medical therapy employed for secondary prophylaxis after non-Q-wave MI has failed to show a convincing therapeutic rationale for beta blocker administration. In contrast, diltiazem has been shown to influence the early and late outcome following non-Q-wave MI favorably.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575021 TI - Review of beta blocker myocardial infarction trials. AB - This is a brief review of the current state of knowledge of beta adrenergic blocking agents in the treatment of acute myocardial infarction. Their effects when administered in the acute phase of infarction, and in special subgroups of patients who have sustained an acute infarction, are discussed. Particular emphasis is directed to their effect on arrhythmias and in patients with left ventricular dysfunction. In addition, data are presented which suggest the advantage of permanent therapy of beta blockers in patients who have sustained a myocardial infarction and in whom the drug is tolerated. PMID- 2575022 TI - Can prognosis be altered by treating LV dysfunction? AB - A major scientific effort taking place in the last decade has resulted in better understanding of the pathophysiology of myocardial dysfunction and in the development of new therapeutic modalities for this condition. The purpose of this article is to review available information related to the effect of available therapeutic modalities on mortality rate in patients with left ventricular (LV) systolic dysfunction. PMID- 2575023 TI - Anti-CD3 and anti-CD2-induced T-cell activation in primary Sjogren's syndrome. AB - Because T-cell dysfunctions have been reported in patients with primary Sjogren's syndrome (SS), peripheral blood mononuclear cell (PBMC) proliferation obtained with anti-CD3 and anti-CD2 monoclonal antibodies was evaluated in these patients. Anti-CD3-induced mitogenesis, which varied widely among the patients, was lower in subjects with evidence of anti-SSA and anti-SSB antibodies than in controls. Moreover, the anti-CD2-induced response was depressed in about half the patients and the nonresponders were mainly those with anti-SSA and anti-SSB antibodies. Phorbol myristate acetate, a protein kinase C activator, used alone or added to anti-CD3, induced greater proliferation in patients than in control PBMC. In contrast, exogenous recombinant interleukin 2 (rIL-2) did not significantly enhance the anti-CD2-induced response of patients' PBMC, as it did in normal PBMC. Peripheral blood and parotid T cells from a patient with well-defined primary SS and parotid enlargement also responded poorly to anti-CD2 stimulation. Exogenous rIL-2 restored T-cell proliferation only in the salivary gland cultures of this patient. The present findings suggest that there is a T-cell activation defect in subjects with primary SS, particularly in those with circulating anti SSA and anti-SSB antibodies. In addition, the difference in the response to IL-2 of peripheral blood and parotid-infiltrating T cells would seem to indicate that T-cell subsets are differently distributed in the blood and inflammation site. PMID- 2575024 TI - Mechanisms of action of slow-acting drugs in rheumatoid arthritis. AB - Slow-acting anti-rheumatic drugs exhibit a number of similar properties in treated patients that suggest that they may have a common mode of action in rheumatoid arthritis. In vitro evaluation of drug action suggests that each of the slow-acting agents possesses immunosuppressive activity that may explain its therapeutic efficacy in rheumatoid arthritis. Even though these agents appear to be able to suppress immune responses, the site of action of these agents differs. Thus, gold compounds and the antimalarials suppress the activity of mononuclear phagocytes, whereas D-penicillamine and other thiol-containing slow-acting agents inhibit the activity of helper T cells. These agents may therefore be effective by interfering with various specific aspects of the immunologic reactivity that drives the chronic inflammation of rheumatoid arthritis. PMID- 2575025 TI - A new hypoglycemic agent, midaglizole, blunts diabetic platelet aggregation: a possible role of alpha 2 blockade. AB - A newly developed alpha 2 blocker, midaglizole (DG-5128, 2-[2-(4,5-dihydro-1H imidazol-2-yl)-1-phenylethyl] pyridine dihydrochloride sesquihydrate) has been shown to have a hypoglycemic action in healthy controls as well as in diabetics. Since human platelets are rich in alpha 2 receptors, the effects of midaglizole on platelet aggregation were investigated. In normal controls, ADP- or epinephrine-induced platelet aggregation was significantly inhibited 2 h after oral administration of 300 mg midaglizole. Midaglizole also suppressed diabetic platelet aggregation stimulated by 10 or 100 microM epinephrine and delayed the initiation of collagen-induced aggregation at 30 micrograms/ml. In vitro addition of midaglizole at 9 or 90 microM significantly inhibited epinephrine-induced platelet aggregation. Furthermore, long-term administration of midaglizole suppressed diabetic platelet aggregation induced by 0.5-1 microM ADP or 1 microM epinephrine. These results suggest that alpha 2 blockade not only blunts diabetic epinephrine-induced platelet aggregation but also affects ADP- or collagen stimulated platelet aggregation, indicating that this alpha 2 blocker may offer a new approach to the treatment of diabetic microangiopathy. PMID- 2575026 TI - [Epidemic hemorrhagic fever during pregnancy]. PMID- 2575027 TI - Maternal somatostatin levels and their correlation with infant birth weight. AB - Samples of blood were obtained from 52 primiparous breast-feeding women 4 days post partum. Thirty-six of the mothers were still breast-feeding 3-4 months later and had further blood samples taken. Somatostatin levels were analyzed by radioimmunoassay. A highly significant rank correlation (P = 0.0001) between average somatostatin levels on the two occasions was established, although somatostatin levels recorded 3-4 months post partum were significantly higher than those found 4 days post partum (P less than 0.01). Furthermore, somatostatin levels obtained 4 days and 3-4 months post partum were inversely related to the birth weight of their children (P = 0.006 and P = 0.03). The significant negative correlation between somatostatin levels recorded 4 days post partum and birth weight of the infants persisted only when non-smokers were investigated. A strong positive correlation between infant birth weight and weight of placenta was found (P = 0.0001) and a negative correlation (P = 0.04) between somatostatin levels and placental weight. A stepwise regression was performed to explain the importance of somatostatin levels in birth weight. Somatostatin levels and smoking had an almost equal influence on the variation in birth weight (approximately 10%). It is suggested that low maternal somatostatin levels are related to an efficient storage of nutrients in the fetoplacental unit, thereby leading to a high birth weight. PMID- 2575028 TI - Treatment of stones in the bile duct via duodenoscopy. PMID- 2575029 TI - Neuroendocrine response in acute heart failure and the influence of treatment. AB - Vasoactive humoral factors were measured in 27 patients before and during the first week of conventional treatment of acute heart failure. On admission, all patients were given frusemide intravenously, followed by oral digoxin and diuretic therapy. Before drug treatment, plasma renin activity and plasma angiotensin II concentrations were within normal ranges in the group of patients without previous diuretic treatment, but were significantly higher in those 16 patients already on diuretic drugs when admitted to hospital. After diuretic treatment, however, even the former group revealed activation of the renin angiotensin system. Plasma concentrations of catecholamines were increased initially but normalized within 1 day. A majority of the patients initially had very high plasma concentrations of atrial natriuretic peptide (mean 276.9 +/- 39.0 pg ml-1) which decreased but did not normalize during the study period. High plasma levels of arginine vasopressin (mean 56.8 +/- 14.6 pg ml-1) were found, but tended to be reduced during treatment. Thus, patients with acute heart failure displayed increased plasma concentrations of atrial natriuretic peptide, arginine vasopressin and catecholamines, but these vasoactive hormones decreased in parallel to clinical improvement during diuretic therapy. In contrast, the renin-angiotensin system became clearly activated. PMID- 2575030 TI - Chronic granulomatous disease of childhood: gastric manifestation and response to salazosulfapyridine therapy. AB - The case history of a 10-year-old boy with chronic granulomatous disease (CGD) and gastric obstruction is presented. First abdominal symptoms occurred at 4 years of age when antral narrowing was detected. Due to unresponsiveness to antibiotic and steroid treatment, salazosulfapyridine therapy was initiated. Objective remission was observed within 3 months and salazosulfapyridine was withdrawn after a further 6 months of therapy. At 6 years of age clinical and radiological recurrence of gastric obstruction was observed. Salazosulfapyridine was reinstated and continued as maintenance therapy. The child has been well for more than 4 years. Salazosulfapyridine therapy can be recommended as safe conservative treatment of gastric obstruction in CGD. PMID- 2575031 TI - In vivo administration of interleukin 1 elicits increased Ia antigen expression on B cells through the induction of interleukin 4. AB - The effects of the in vivo administration of interleukin 1 (IL 1) on lymphocytes from lymph node and spleen were analyzed. Mice received five daily subcutaneous (s.c.) injections of various doses of human recombinant IL 1 beta. Either 1 or 7 days after IL 1 treatment, spleens, popliteal and inguinal lymph nodes were collected. Lymphadenosis and splenomegaly were observed in the IL 1-treated animals. Lymph nodes from IL 1-treated mice contained a higher percentage of B cells than controls, and B cells from IL 1-treated mice expressed dramatically increased levels of Ia antigen. Lymphadenosis and splenomegaly, as well as the changes in subset distributions and Ia expression were transient. Concomitant treatment of mice with IL 1 and anti-IL 4 monoclonal antibody suppressed IL 1 effects on B cell Ia expression, but not on the B/T cell ratio. In situ hybridization analyses revealed that IL 1 treatment induced the expression of mRNA for IL 4, interferon-gamma, and IL 2 in lymph node and spleen cells. The distribution of cells expressing the various cytokine mRNA was markedly different between the spleens and lymph nodes. PMID- 2575032 TI - Expression and function of CD2 during murine thymocyte ontogeny. AB - CD2, originally recognized as the sheep erythrocyte receptor of human T cells, has been implicated in early T cell development in the thymus. In this report, we examined the expression and functional role of CD2 during murine thymocyte ontogeny by using monoclonal antibodies to murine CD2. Surface expression of CD2 was first detected in Thy-1+ fetal thymocytes at day 14 of gestation and it progressively increased during CD4-CD8- phenotype. Surface IL 2 receptor (CD25) expression was readily detected in surface CD2- cells at day 13 of gestation and the majority of CD2+ cells appeared to be generated from CD25+ cells thereafter. In adult CD4-CD8- thymocytes, the expression of CD2 and CD25 was mutually exclusive. These results indicate that surface CD2 expression is not a prerequisite for CD25 induction during murine thymocyte ontogeny. This was further confirmed by fetal thymus organ culture in which anti-murine CD2 mAb was included. The antibody treatment led to a suppressed CD2 expression on thymocytes; however, there was no effect on the appearance of CD25. Moreover, no influence on the development of mature CD3+ thymocytes was observed after fetal thymus organ culture in the presence of anti-murine CD2 mAb, and a substantial number of CD3+CD2- cells was demonstrated in fetal and adult CD4-CD8- thymocytes. These findings argue against the functional relevance of CD2 expression during early T cell development as proposed in humans. PMID- 2575033 TI - T cell receptor gene expression in sheep: differential usage of TcR1 in the periphery and thymus. AB - We have isolated cDNA clones for each chain of the sheep T cell receptor (TcR) and used these to analyze TcR gene expression in thymocyte and peripheral T cell subsets. Outer cortical thymocytes expressed a low level of mature message for all TcR chains suggesting that intrathymic precursors for the alpha/beta and gamma/delta lineages occur in this population. Inner cortical and medullary thymocytes expressed high levels of mature alpha/beta transcripts, low levels of mature delta transcripts but no detectable gamma message. Mature alpha/beta transcripts were detected in peripheral CD4+ lymphocytes and these as well as CD8+ cells expressed a surface heterodimer of 85 kDa which resolved into 40- and 50-kDa subunits after reduction. Peripheral CD4-CD8-lymphocytes, which in sheep are marked by the T19 antigen and may account for up to 60% of T cells in blood, expressed a surface heterodimer of 75 kDa. The T19+ cells had high levels of mature delta and truncated beta transcripts in their cytoplasm but did not express the C gamma gene detected in DN thymocytes, although they seem to share V gamma and/or J gamma elements. Both forms of the sheep TcR are associated with CD3 molecules on the cell surface. These results show that (a) in contrast to the situation in rodents and humans, a large proportion of peripheral sheep lymphocytes use TcR gamma/delta; (b) the proportion of T cells in the periphery which use TcR gamma/delta is greater than in thymus; and (c) CD4-CD8- cells in thymus and periphery (T19+) use the same C delta gene but appear to use different C gamma genes, suggesting that in sheep there may be more than one lineage of lymphocytes expressing TcR gamma/delta. PMID- 2575034 TI - Cholera toxin modulates the T cell antigen receptor/CD3 complex but not the CD2 molecule and inhibits signaling via both receptor structures in the human T cell lymphoma Jurkat. AB - The human T cell lymphoma Jurkat can be activated by stimuli directed either against the T cell antigen receptor-CD3 antigen complex (TcR/CD3) or the CD2 molecule. Stimulation of cells via the TcR/CD3-complex or via the CD2 molecule increases inositol phosphates and cytoplasmic free calcium. Pretreatment of Jurkat cells with cholera toxin leads to a decrease of TcR/CD3 expression on the surface of the cells, while the expression of CD2 is unaffected. In contrast to this distinct effect on the receptor expression, signaling via both pathways is inhibited by cholera toxin. The most convincing explanation for the cholera toxin mediated inhibition of signaling is that cholera toxin interrupts the signaling pathways at a point where both, stimulation via TcR/CD3 and via CD2, use the same route. The earliest common point of the two signaling pathways, at least in the Jurkat cell line, seems to be the CD3 complex because after its down-regulation (and functional inactivation) both pathways of activation are interrupted. PMID- 2575035 TI - Further studies on the mechanism of the cardiovascular effects of L-tyrosine. AB - Tyrosine is the precursor amino acid of catecholamines. Low doses of tyrosine produce tachycardia and hypertension, while higher doses induce bradycardia and hypotension in anaesthetised rats. The mechanism and site of action of L-tyrosine are not fully understood. Eight groups of Wistar rats received different pretreatments in order to study the influence of blockade of various receptor mechanisms on the cardiovascular effects of L-tyrosine. The effects mediated by the autonomic nervous system were inhibited by ganglion blockade (hexamethonium), by alpha 1- and beta 1-adrenoceptor blockade (prazosin and atenolol) and by parasympathetic acetylcholine receptor blockade (atropine). The possible role of histamine receptors was studied by inducing H1 and H2-receptor blockade (diphenhydramine and cimetidine, respectively). The effect of inhibition of prostaglandin synthesis by indomethacin was also studied. The L-tyrosine-induced tachycardia was completely blocked by atenolol. Both atenolol and prazosin partly inhibited the hypertensive effects of low doses of tyrosine. The tyrosine-induced bradycardia was not inhibited, and the hypotension was only partly blocked by the pretreatments. Therefore, adrenergic mechanisms seem to mediate the stimulatory cardiovascular effects of tyrosine. The depressant effects of high doses of tyrosine do not appear to be mediated by cholinergic activation, histamine receptor activation, or prostaglandin synthesis. PMID- 2575036 TI - Inhibition of dopamine release by methylenedioxymethamphetamine is mediated by serotonin. AB - (+/-)-3,4-Methylenedioxymethamphetamine (MDMA), at doses of 0.1, 1 and 10 mg/kg, produced a long-lasting decrease in extracellular dopamine concentration in the neostriatum of anesthetized rats, as measured by in vivo voltammetry. Since MDMA has been shown to release serotonin from rat brain slices and synaptosomes, we examined the possibility that increased serotonin release might be the cause of the decrease in dopamine release. Rats were treated with d,l-p-chloroamphetamine seven days prior to acute MDMA administration. Rats pretreated with p chloroamphetamine, which produced a marked decrease in serotonin content, showed no significant decrease in extracellular dopamine concentration when administered 10 mg/kg MDMA. These data suggest that MDMA produces a significant decrease in dopamine release when administered acutely, and that this decrease is an indirect effect mediated by an increase in serotonin release. PMID- 2575037 TI - Chronic phenytoin treatment decreases GABAA but not beta-adrenoceptors in the cerebellum of young rats. AB - The effects of chronic treatment with phenytoin (50 mg/kg p.o. daily, for the first 30 days after birth) on GABAA and beta-adrenoceptors in the rat cerebellum were investigated by using in vitro quantitative autoradiography and binding assays with membranes. A significant decrease in [3H]muscimol binding to GABAA sites and, to a lesser extent, [3H]flunitrazepam binding to benzodiazepine sites was observed in the granular and molecular layers of the cerebellar cortex at the end of the treatment. Scatchard analyses demonstrated that these effects were associated with a decreased Bmax for the respective binding sites in cerebellar membranes the (Kd was not changed). In contrast, [125I]cyanopindolol binding remained unaffected. These data provide further support for the involvement of GABAergic synapses in the anticonvulsant action of phenytoin. PMID- 2575038 TI - Effects of fenoldopam on alpha-methyl-p-tyrosine-stimulated prolactin secretion in conscious rats. AB - Pituitary dopamine D-2 receptors participate in the regulation of prolactin (PRL) release. No dopamine D-1 receptors have so far been identified in the pituitary gland. The present study was designed to assess the effects of fenoldopam, a selective dopamine D-1 receptor agonist, on alpha-methyl-p-tyrosine-stimulated PRL release. Fenoldopam dose dependently reduced the alpha-methyl-p-tyrosine stimulated PRL secretion. This inhibitory effect of fenoldopam was abolished after pretreatment with SCH 23390, a specific dopamine D-1 receptor antagonist, suggesting the involvement of a dopamine D-1 receptor in PRL secretion. PMID- 2575039 TI - Comparison of the purinergic contribution to sympathetic vascular responses in SHR and WKY rats in vitro and in vivo. AB - Isolated tail arteries from spontaneously hypertensive rats (SHR) were more responsive than those from Wistar-Kyoto (WKY) control rats to exogenously applied noradrenaline (NA), ATP, alpha,beta-methylene ATP (mATP), KCl and sympathetic nerve stimulation. The sympathetic contractile responses of the SHR and WKY were both reduced to 10-20% of control by alpha 1-adrenoceptor antagonism. The pressor responses to sympathetic nerve stimulation were significantly greater in the SHR than the WKY rats at all stimulation frequencies examined (1-10 Hz). There was no significant difference between SHR and WKY rats in the magnitude of pressor responses produced by i.v. administration of NA or mATP. The pressor responses to sympathetic nerve stimulation in the pithed SHR were no more resistant to alpha adrenoceptor antagonism than those of the WKY. The results suggest that the contribution by ATP to sympathetic vasoconstriction is no greater in SHR than WKY. PMID- 2575040 TI - Characterization of histamine H1-receptors on astrocytes in primary culture: [3H]mepyramine binding studies. AB - The characteristics of histamine H1-receptors on astrocytes from the cerebral cortex of newborn rats in primary culture were analyzed with a [3H]mepyramine binding assay, and compared with those in the cerebral cortex. The apparent dissociation constant (KD) of [3H]mepyramine binding, the apparent inhibition constants (Ki) of various H1-ligands for [3H]mepyramine binding and the stereoselectivity of d- and l-chlorpheniramine for the inhibition of [3H]mepyramine binding to receptors on cultured astrocytes and to receptors in the brain tissue were very similar, indicating that these receptors are identical. The apparent density of H1-receptors (Bmax) on astrocytes was 262 +/- 60 fmol/mg protein, which was comparable to that in the brain tissue (194 +/- 24 fmol/mg protein). The development of H1-receptors on cultured astrocytes resembled the postnatal development of the receptors in the rat brain. These results suggest that astrocytes could be one of the main targets of the central histaminergic system. PMID- 2575041 TI - Regulation of beta 1- and beta 2-adrenoceptors following chronic treatment with beta-adrenoceptor antagonists. AB - The effect of chronic pretreatment of guinea pigs with various beta-adrenoceptor antagonists on the binding characteristics of the radioligand 125I-cyanopindolol (ICYP) and responsiveness of adenylate cyclase to isoprenaline in the gastrocnemius muscle (beta 2-adrenoceptors) and the left ventricle (beta 1 adrenoceptors) were compared. Pretreatment of guinea pigs with propranolol or ICI 118,551 for one week significantly increased the density of the beta 2 adrenoceptors in the gastrocnemius muscle. Atenolol pretreatment for one week did not affect the density of the receptors. Pretreatment of the animals with pindolol for one week reduced the density of beta 2-adrenoceptors in skeletal muscle. In the left ventricle pretreatment of the guinea pigs with any of the antagonists did not alter either the density or the KD of beta 1-adrenoceptors. The responsiveness of adenylate cyclase to isoprenaline (10(-4) M) in the left ventricle or skeletal muscle was not affected when the guinea pigs were pretreated with propranolol. Pretreatment of the guinea pigs with reserpine (0.5 mg.kg-1) intraperitoneally for one week, to deplete catecholamines did not affect beta-adrenoceptor density or KD in the left ventricle or skeletal muscle. We conclude that the regulation of beta-adrenoceptors by the antagonist may not be caused by the prevention of the access of endogenous agonists to beta adrenoceptors and it is dependent on the selectivity of the antagonist and on the susceptibility of the receptors to regulation. PMID- 2575042 TI - Review of alpha adrenoceptor function in the eye. AB - The location and function of alpha adrenoceptors in the eye are reviewed with emphasis on pharmacological agents and their role in the management of chronic simple glaucoma. PMID- 2575043 TI - A new risk of anaphylaxis. PMID- 2575044 TI - Update on delivery following prior cesarean section: a 15-year review 1972-1987. AB - Fear of true rupture remains the main indication for repeat section. Between 1972 and 1987 there were 2434 patients with one or more prior section and 1350 (55%) were permitted trial of labor, the remainder, having had two or more previous sections (maximum number, 10), had repeat surgery. Induction was employed in 31% and oxytocin for induction or acceleration in 32% patients. The first period (1972-1982) had 844 and the second period (1982-1987) had 506 trial of labor patients. Improved management resulted in the true rupture rate falling from 0.6% (1:169) to 0.2% (1:506) and the elimination of procedure-related perinatal death. There were two maternal deaths with repeat section and none with trial of labor. We have achieved a plateau for cesarean section (10-11%) and a continuing fall in the uncorrected hospital perinatal mortality, which has averaged 10.6/1000 for the years 1982-1986 inclusive. PMID- 2575045 TI - The effect of hypertension in pregnancy on fetal and neonatal condition. AB - The aim of this prospective study was to determine the effect of hypertension in pregnancy (PH) on fetal and neonatal condition via other mechanisms than retarded intrauterine growth and preterm delivery. Sixty-six preterm and 175 full-term babies born to PH mothers were compared, respectively, with 183 preterm and 220 full-term babies born to non-hypertensive (non-PH) mothers over a 22-month period in 1984-1986. Small-for-gestational-age (SGA) children were examined separately from appropriate-for-gestational-age (AGA) children. Percentages of preterm babies and of both preterm and full-term SGA babies born to hypertensive mothers were twice as great as the percentages of such babies born to non-hypertensive mothers. Hypertension in pregnancy directly increased neonatal morbidity, but the effect was minor. In preterm babies it was related to intrauterine growth retardation and to pre-eclampsia. In full-term babies the effect was unrelated to the severity of hypertension. PMID- 2575046 TI - Cervical prostaglandin injection: a novel method of administration for ripening the cervix and induction of labor. AB - Twenty pregnant women with greater than or equal to 36 weeks gestation and Bishop score of less than or equal to 4 were subjected to either intracervical injection of PGE2 (0.25 mg) every 4 h to ripen the cervix and induce labor (study group n = 10) or injection of only the diluent (control group n = 10). PGE2 cases showed significant increase in Bishop score and were successfully induced. The mean induction-establishment and induction-delivery intervals were 4.3 +/- 0.1 min and 6.07 +/- 1.7 h, respectively. The control group showed no response. PGE2 cervical injection is a safe and effective method for cervical ripening and labor induction. PMID- 2575047 TI - Initiation of labor with a moderately favorable cervix: a comparison between prostaglandin E2 gel and oxytocin. AB - This study compares prostaglandin E2 (PGE2) gel and oxytocin for the initiation of labor in term pregnancies with a moderately favorable cervix (Bishop score 5 8). Compared with a matched group, 48 cases treated with PGE2 gel (2.5 mg intravaginally) required significantly less or no oxytocin, had shorter first stages of active labor, and had no increased risk of uterine hyperstimulation or cesarean section. Initiation of labor with low dose PGE2 when the cervix is moderately favorable is less labor intensive and meets with more patient satisfaction. PMID- 2575048 TI - Prevalence of genital herpes simplex infection and abnormal vaginal cytology in late pregnancy in asymptomatic patients. AB - A study was undertaken to determine the prevalence of genital herpes simplex virus (HSV) infection in 809 asymptomatic, late pregnant women attending the antenatal clinic (ANC) at Ramathibodi Hospital. There was only one case where the cervico-vaginal swab specimen was positive for HSV by cultivation and the biotin streptavidin enzyme-linked immunosorbent assay (B-SA ELISA), for detection of viral antigens. This gave a prevalence rate of 0.12%. The anti-HSV IgM in cord blood of the infant born to this mother was negative. The Papanicolaou (Pap) smear was performed in 554 cases, including the above patient, but none showed evidence of HSV infection. The high prevalence of lower genital tract infection in these subjects was noted in both Pap smear (31.05%) and wet preparation of the cervico-vaginal discharge (46.72%). Thus, examination of the cervico-vaginal discharge during late pregnancy should be of benefit to the patients, in revealing asymptomatic infections of the lower genital tract. PMID- 2575049 TI - Improved fetal survival with small volume plasmapheresis in Rhesus disease. AB - Fifty pregnant multiparas with Rhesus isoimmunization were treated by small volume plasmapheresis initiated at the end of their first trimester. Forty mothers were successfully delivered at 31-38 weeks of babies that survived. There were ten fetal losses, six of these were stillborn, and there were three neonatal deaths, and one abortion. This fetal survival rate is acceptable, and plasmapheresis remains an alternative therapy in locations where immunoprophylaxis is not common. PMID- 2575050 TI - Breech delivery in a Middle East hospital. AB - This paper provides an analysis of the results of 206 deliveries in which the patient's preference influenced the mode of delivery. PMID- 2575051 TI - Fertility after ectopic pregnancy in an African population. AB - Cases of ectopic pregnancy were studied retrospectively at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria, for the period from January 1, 1977 to June 30, 1987. The records of 108 patients who had at least 1 year of follow-up were reviewed to determine their subsequent reproductive performance. Thirty-eight patients (35.9%) subsequently conceived, 15 (13.9%) had recurrent ectopic pregnancy, 21 (19.4%) delivered at term, and 40 (37%) remained secondarily infertile. Thirty patients were sterilized or using contraception. PMID- 2575052 TI - Laparoscopic adhesiolysis for infertile patients with pelvic adhesive disease. AB - Thirty patients with secondary infertility were subjected to laparoscopic adhesiolysis during the period January 1986 to February 1987 at Al-Azhar Endoscopy and Microsurgery Unit. Second look laparoscopy (SLL) was performed after a period of 9-12 months. At laparoscopy, pelvic adhesive disease was staged according to the severity of the disease and compared with the finding at SLL. Five patients defaulted, three patients (12%) became pregnant and 22 patients underwent SLL. Ten patients (45.5%) showed no recurrence of adhesions. This study suggests that laparoscopy has a role in adhesiolysis of mild and moderate adhesions and SLL provides further opportunity to relyse reformed adhesions in some cases. PMID- 2575053 TI - Topical testosterone for lichen sclerosus. AB - Twenty-three patients diagnosed as lichen sclerosus with colposcopic directed biopsy were given topical testosterone as a first line therapy. The overall remission rate was found to be 87.7%; 8.7% of the patients experienced undesirable androgenic side effects. Of the three patients who did not respond satisfactorily to testosterone treatment, two had alcohol injection to the vulva and one had vulvar denervation. PMID- 2575055 TI - Successful pregnancy in a renal transplant recipient taking cyclosporin A: hormonal and immunological studies. AB - A successful pregnancy following renal allotransplantation is reported. Until now azathioprine has been used as the standard immunosuppressive agent in such cases. Because of the potential teratogenicity of azathioprine, low doses of cyclosporin A, a new immunosuppressive drug, was used in our pregnant recipient. We present the management and the outcome of the pregnancy, as well as the hormonal and immunological follow up. PMID- 2575054 TI - Tubal ligation at cesarean delivery in five Asian centers: a comparison with tubal ligation soon after vaginal delivery. AB - Increasingly more tubal sterilizations are being performed at the time of cesarean section in the United States and probably also in developing countries. This descriptive study provides us with hitherto unavailable information on the impact of this combined procedure on the women undergoing it. Five Asian centers were included for study. In these centers, 618 women had concurrent tubal ligation at cesarean section in 1973 and 1974. During this period, 3399 women had tubal ligation soon after term vaginal deliveries. The much higher morbidity and mortality in the former group were judged to be attributable to the indications leading to, or the complications of, cesarean section and not to the concurrent tubal ligation. Women undergoing the combined procedure of tubal ligation and cesarean section were more likely to have characteristics associated with later regretting the sterilization. PMID- 2575056 TI - Combined pregnancy: how common is it? AB - Three cases of combined intrauterine and ectopic pregnancy, treated in the same hospital over a 39-day period, are presented. This condition has been acknowledged to be a rare phenomenon with delayed diagnosis and treatment. Two of the cases were diagnosed by ultrasound upon arrival at the hospital, and all three were treated within 24 h of arrival. These cases highlight the importance of ultrasound in diagnostics and indicate a possible higher incidence of this phenomenon than was previously estimated. PMID- 2575057 TI - Intussusception: a rare complication following abdominal hysterectomy. AB - A 35-year-old parous woman was treated with abdominal hysterectomy for uterine myomata. The patient developed intussusception in the immediate postoperative period and was managed by laparotomy and manual reduction. The difficulties in diagnosis and management of this rare complication are discussed. PMID- 2575058 TI - Actinomycosis mimicking pelvic malignancy. AB - Pelvic actinomyces, usually a complication of an intrauterine device (IUD), is uncommon and may present a diagnostic dilemma because of an atypical clinical presentation. We present a patient with a cervical tumor, extensive parametrial induration with involvement of the posterior bladder wall, and regional lymph nodes which mimicked advanced cervical cancer and presented a significant diagnostic problem. PMID- 2575059 TI - Tensile strength of Cr-Co dental alloys solder joints. AB - Modifications and repairs of removable partial dentures usually involve solder joints. It is important to know the combination of solder and alloy that will provide the strongest junction. The purpose of this work was to investigate the mechanical strengths of different solders commonly used in dental practice. Specimens of three removable partial denture alloys (Dentitan, Crutanium, Wisil) were soldered with various solders having different melting temperatures. The soldered specimens were subjected to tensile testing, and the fracture surfaces were examined by means of scanning electron microscopy. Most of the failures occurred within the soldered joint, which is the weakest portion of a removable partial denture. Excessive use of flux to achieve an adequate flow of solder produced defects in the solder joint. A relationship was found between joint strength and solder fusion temperature for Crutanium and Wisil--the higher the fusion temperature, the higher the joint strength. PMID- 2575060 TI - Omeprazole in the treatment of Zollinger-Ellison syndrome and histamine H2 antagonist refractory ulcers. AB - Omeprazole is a very potent and long-acting inhibitor of gastric acid secretion. These characteristics make the drug very suitable for the management of gastric acid hypersecretion and symptom relief in patients with the Zollinger-Ellison syndrome, and in the treatment of patients with ulcers resistant to histamine H2 receptor antagonists. Most patients require only a once-daily dose, whereas in about 30% of patients with Zollinger-Ellison syndrome the dose has to be split. During long-term treatment the required dose of omeprazole is usually rather stable. Up until now neither in patients with Zollinger-Ellison syndrome nor in those with resistant ulcers have convincing reports of resistance to omeprazole been published. However, a relative disadvantage of omeprazole is the observation that symptom-free Zollinger-Ellison syndrome patients are less inclined to undergo the work-up for surgery, which is the only possible curative treatment for these patients. Omeprazole therapy has been well tolerated and no side effects, significant changes in laboratory variables or toxicity have been noted. PMID- 2575061 TI - Treatment of reflux oesophagitis resistant to H2-receptor antagonists. AB - Results of medical therapy of reflux oesophagitis are disappointing, especially compared to the success obtained in peptic ulcer disease. H2-receptor antagonists, with or without the addition of mucosaprotectiva or prokinetica, produce healing only in 50% of the patients. Nowadays, even severe, resistant reflux oesophagitis can be treated successfully with the H+/K+-adenosine triphosphatase antagonist omeprazole. Experience of more than 3 years of continuous treatment with omeprazole, in doses which have been adjusted to prevent recurrences, has also demonstrated its high efficacy in the long-term management of the patients. The use of this drug emphasizes the importance of long-standing, strong acid inhibition for this condition, although careful surveillance of the safety profile of this drug remains obligatory. PMID- 2575062 TI - Management of gastro-oesophageal reflux disease. Are there alternatives to omeprazole? AB - Several studies have clearly demonstrated that omeprazole is highly efficacious in the management of patients with gastro-oesophageal reflux disease. In particular, wherever H2-receptor antagonists fail to produce results--in patients with severe disease--omeprazole has been shown to be of major value. However, new alternatives are forthcoming; a new generation of more potent H2-receptor antagonists will be available, while 24 pH studies with high-dose ranitidine have shown that acid reflux is suppressed more efficiently than with standard doses. The prokinetic drug cisapride appears to be of importance, not only in the management of patients with mild reflux disease, but also of cases with severe disease when cisapride is combined with a H2-receptor antagonist. Such a combination could also be of value as an alternative to omeprazole in long-term therapy, since it has not yet been shown that indefinite treatment with omeprazole of patients with reflux disease will be safe. In addition, the value of long-term sucralfate, effective in short-term therapy, needs to be evaluated in patients with chronic reflux disease who will not be operated. In forthcoming studies, it will be advisable to incorporate 24-hour pH measurements to detect periods of nonacid suppression more accurately. The future of medical management of gastro-oesophageal reflux disease appears to be promising. PMID- 2575063 TI - Somatostatin receptors and the effect of somatostatin on histamine-stimulated adenylate cyclase activity in isolated gastric glands of guinea pigs. AB - To investigate the mechanism of the suppressive action of somatostatin on gastric acid secretion, we determined the somatostatin binding and adenylate cyclase activity on crude membrane fractions of isolated gastric glands of guinea pigs. The binding studies using 125I-Tyr11 somatostatin showed the presence of somatostatin receptors with a single high affinity on crude membrane fractions. The dissociation constant (KD) for somatostatin was 1.05 +/- 0.13 nM, and the number of binding sites (Bmax) was 6.98 +/- 1.27 fmol/mg protein (mean +/- SE, n = 6). The adenylate cyclase activity was increased by histamine, which was completely inhibited by 10(-3) M cimetidine. Somatostatin non-competitively suppressed the histamine-stimulated adenylate cyclase activity in the presence of guanosine 5'-triphosphate (GTP). These results suggest that somatostatin inhibits histamine-stimulated acid secretion through the inhibition of the adenylate cyclase system, via somatostatin receptor and guanine nucleotide binding protein, which is activated by GTP binding. PMID- 2575064 TI - Comparative effects of verapamil and D-600 on the contractile responses produced by neurotransmitters and depolarizing agents in the rat isolated seminal vesicle. AB - 1. The comparative effects of verapamil and D-600, on isometric contractions produced by noradrenaline, acetylcholine, phenylephrine, clonidine, carbachol and high potassium, were studied in rat isolated seminal vesicle. 2. The aim was to see if verapamil and D-600 differed, in their selectivity, of blocking calcium, channels, and hence inhibition of isometric contractions produced in this preparation. 3. Verapamil (1 microM) and D-600 (9.5 microM), selectively, reduced the isometric contractions, greater reductions occurred in the KCl-induced contractions (control EC50 19 +/- 1.5 mM, in verapamil 58 +/- 1.3 mM, and in D 600 37 +/- 2.0 mM, means +/- SE, n = 8, P less than 0.001, less than 0.01, respectively). 4. It was concluded that KCl-induced contractions were voltage dependent, whereas noradrenaline operated via both voltage and receptor-mediated mechanisms. 5. The clinical relevance of these results was discussed, and it may help our current understanding of the pharmacological management of sexual dysfunction. PMID- 2575065 TI - Two phases in the addition of a poly(A) tail. AB - The addition of a poly(A) tail has been examined in a HeLa cell nuclear extract using SV40 late RNAs that end at or near the natural poly(A) site. We find that the addition of a full-length, 200-nucleotide poly(A) tail occurs in two discrete phases. In the first phase, the addition of each adenosine is dependent on the highly conserved sequence AAUAAA. Mutations in that sequence result in an accumulation of products that contain 9 or fewer adenosine residues. In the second phase, poly(A) addition no longer requires AAUAAA but, instead, requires the oligo(A) primer synthesized during the first phase. Thus, RNAs carrying an AAUAAA mutation and a 3'-terminal oligo(A) segment are extended efficiently to full-length poly(A). The transition between phases occurs with the addition of the tenth adenosine residue. An activity exists that limits the length of poly(A) added in the extract to approximately 200 nucleotides. The two phases share at least one component and are likely to involve the same poly(A) polymerase. PMID- 2575066 TI - The molecular genetics of the bithorax complex of Drosophila: characterization of the products of the Abdominal-B domain. AB - In Drosophila the Abdominal-B (Abd-B) domain of the bithorax complex specifies the identities of several posterior abdominal segments, comprises homeo-protein coding regions and cis-regulatory regions, and extends from infra-abdominal-5 (iab-5) to iab-8, inclusive. Mutations that eliminate the Abd-B domain act as late embryonic lethals and result in transformations of posterior abdominal segments toward more anterior ones. The Abd-B domain gives rise to a minimum of five homeo-box-containing transcripts, 7.8, 4.7, 4.3, 3.7, and 3.3 kb in length. We examined the structure of the Abd-B domain by sequencing two Abd-B cDNA clones derived from the 4.3- and the 4.7-kb transcripts and the corresponding genomic DNA. The domain spans approximately 100 kb and contains at least eight exons. The 4.7- and 4.3-kb transcripts contain an open reading frame capable of encoding a 54-kD protein. A portion of the deduced protein-coding sequence common to all of the Abd-B transcripts was cloned into an expression vector. The resultant fusion protein then was used to derive a monoclonal antibody specific to Abd-B. By use of that antibody, we identified two embryonic Abd-B proteins, 54 and 36 kD and determined the sum of their segmental distribution by immunohistochemical analysis of whole-mounted embryos and immunofluorescent analysis of dissected embryonic nervous systems. The proteins are distributed in the fourth to the ninth abdominal segments [parasegments (PS) 10-15] inclusive. Embryos homozygous for Polycomb (Pc) show labeling over almost the entire embryo, whereas embryos deficient for the Abd-B domain show no detectable labeling. PMID- 2575067 TI - [The significance of molecular biology in hypertension research]. PMID- 2575068 TI - Noradrenaline release in human corpus cavernosum and its modulation via presynaptic alpha 2-adrenoceptors. AB - Strips of human corpus cavernosum were incubated with 3H-noradrenaline and subsequently superfused with physiological salt solution containing desipramine and corticosterone. The electrically (0.66 Hz) evoked tritium overflow was abolished by tetrodotoxin or omission of Ca2+ from the superfusion fluid. The alpha 2-adrenoceptor agonist B-HT 920 (6-allyl-2-amino-5, 6, 7, 8-4H-thiazolo-5,4 d-azepine), inhibited the evoked overflow, whereas the alpha 1-adrenoceptor agonist, methoxamine, was ineffective. The alpha 2-adrenoceptor antagonist, rauwolscine, facilitated the evoked tritium overflow. It is concluded that the stimulation-evoked release of noradrenaline from the sympathetic nerve fibres of the human corpus cavernosum is modulated via presynaptic alpha 2-adrenoceptors. PMID- 2575069 TI - Three F XIIIA gene loci? PMID- 2575070 TI - Close linkage of probe p212 (DXS178) to X-linked agammaglobulinemia. AB - Segregation analysis was performed in three families affected in X-linked agammaglobulinemia (XLA) with five polymorphic DNA probes linked to the disease locus. In agreement with previous studies, no recombination was observed with either pXG12 (DXS94) or S21 (DXS17). Segregation analysis was also performed with a marker, p212 (DXS178), which has been shown to be closely linked to pXG12 in normal families. No cross-over with XLA was observed in these three families and in five additional families previously analyzed with DXS17 and DXS94 (z = 5.92 at theta = 0). These data provide evidence against genetic heterogeneity in XLA and indicate the value of probe p212 for carrier detection and prenatal diagnosis of XLA. We were able to estimate the carrier status of six females (out of six) in the three previously unreported families. PMID- 2575071 TI - Haplotype and multipoint linkage analysis in Finnish choroideremia families. AB - Multipoint linkage analysis of choroideremia (TCD) and seven X chromosomal restriction fragment length polymorphisms (RFLPs) was carried out in 18 Finnish TCD families. The data place TCD distal to PGK and DXS72, very close to DXYS1 and DXYS5 (Zmax = 24 at theta = 0) and proximal to DXYS4 and DXYS12. This agrees with the data obtained from other linkage studies and from physical mapping. All the TCD males and carrier females studied have the same DXYS1 allele in coupling with TCD. In Northeastern Finland, 66/69 chromosomes carrying TCD had the same haplotype at loci DXS72, DXYS1, DXYS4, and DXYS12. The same haplotype is seen in only 15/99 chromosomes not carrying TCD. Moreover, in 71/104 non-TCD chromosomes, the haplotype at six marker loci is different from those seen in any of the 76 TCD chromosomes. This supports the previously described hypothesis that the large Northern Finnish choroideremia pedigrees, comprising a total of over 80 living patients representing more than a fifth of all TCD patients described worldwide, carry the same mutation. These linkage and haplotype data provide improved opportunities for prenatal diagnosis based on RFLP studies. PMID- 2575073 TI - Role of cytokines and CD4+ T-cell subsets in the regulation of parasite immunity and disease. AB - CD4+ T cells have been separated into two subsets, designated TH1 and TH2, based upon the repertoire of lymphokines that they produce following stimulation. We have analyzed the role of these T-cell subsets in two chronic parasitic infections, leishmaniasis and schistosomiasis. In both diseases, we found a strong association with TH1 stimulation and protection, and TH2 stimulation and immunopathology. In addition, certain parasite antigens appeared to be strongly linked with either TH1 or TH2 cell development. This led to the establishment of protective T-cell lines and clones in a L. major model, from which we identified a new candidate antigen for vaccination against Leishmania parasites. Moreover, we show that protection against L. major infection can be significantly augmented by coadministration of IFN-gamma with antigen, a lymphokine known to inhibit TH2 cell proliferation. In S. mansoni-infected mice, animals with a patent infection exhibit an overwhelming TH2 response, while animals protectively immunized with irradiated cercariae preferentially produce IFN-gamma, a lymphokine associated with TH1 cell stimulation. In addition, we show that ablation of schistosome induced eosinophilia by in vivo anti-IL-5 monoclonal treatment fails to reduce the protection induced by irradiated cercariae. Similarly, anti-IL-5 treatment resulted in egg-induced granulomas nearly devoid of eosinophils, but only caused a marginal reduction in granuloma size. These results demonstrate that an understanding of the factors controlling TH1 and TH2 development will significantly facilitate the identification and development of vaccines for parasitic infections. PMID- 2575072 TI - A search for restriction fragment length polymorphism on the human Y chromosome. AB - A systematic search for restriction fragment length polymorphisms (RFLPs) on the human Y chromosome was performed. DNA samples from 16-34 individuals were screened with five restriction enzymes and 12 Y-chromosomal probes, 3 of which detect lowly repetitive sequences and 9 of which are apparently single copy in genomic DNA. None of the single-copy probes revealed any variation. The repetitive sequence probe p21A1 (DYZ?) revealed a TaqI RFLP with q = 0.05. The frequency of fixed point mutations in Y-chromosomal DNA outside the pseudoautosomal region is probably less than 1 in 18,000 bp. PMID- 2575074 TI - Tumor-necrosis factor and other cytokines in cerebral malaria: experimental and clinical data. AB - Evidence is presented here that tumor necrosis factor/cachectin (TNF), is of crucial importance in the pathogenesis of cerebral malaria. First, the central lesion of CM, hemorrhagic necrosis of cerebral vessels, corresponds to lesions observed during other pathological conditions associated with high serum TNF levels, such as endotoxemic shock or administration of TNF. Second, in both mouse and human, there is a close correlation between high serum TNF levels and CM. At least in mouse, high TNF levels and CM depend upon T lymphocytes of the CD4+ phenotype. Third, passive immunization against mouse TNF significantly prolongs the survival of P. berghei-infected CBA/Ca mice, and prevents the development of neurologic signs. Treatment with the anti-TNF antibody also prevents hemorrhagic necrosis of brain vessels. Fourth, in the mouse model, a cytokine cascade including at least GM-CSF, IL-3 and IFN-gamma is required for the elevation of TNF level. This cascade appears to involve two components: (a) a quantitative component: increased accumulation of macrophages results from the concomitant release of IL-3 and GM-CSF, and (b) a qualitative component: macrophage number has not only to be raised, but macrophages need to be activated by IFN-gamma. Fifth, metabolic parameters of CM and its main lesion in both mouse and human, i.e. the hemorrhagic necrosis of small brain vessels, correspond to the known properties of TNF. PMID- 2575075 TI - The response of CD4+ T cells to Plasmodium chabaudi chabaudi. AB - We have studied the role of CD4+ T cells in the immune response to Plasmodium chabaudi chabaudi. From in vivo experiments in which the different subsets of T cells were depleted, it is clear that CD4+ T cells are essential for the generation of protective immunity. Our limiting dilution analysis show that the CD4 T-cell response to P. chabaudi antigens is heterogeneous, in that distinct functions can be performed by different responding T cells, and these responses change during infection. During the first phase of the infection the predominant response is that of a TH1-type cell, producing IL-2 and IFN-gamma. This correlates with the appearance of IFN-gamma in the serum of infected animals. After the clearance of the acute parasitemia, i.e. in the second phase of the infection, the specific response is characterised by TH2 cells, which are effective helper cells for antibody production and presumably are necessary for the switch of IgM to IgG. CD4+ T cells are effector cells are not necessary in the second phase of the infection; mice which have been depleted of CD4+ T cells at this time are able to control their infection in a manner similar to untreated mice. This ability to control parasitemia coincides with the production of specific IgG but not IgM antibodies and the predominance of TH2 type helper cells. Therefore, our data suggest that malaria-specific IgG antibodies are important effectors in the second phase of an infection with P. chabaudi chabaudi. PMID- 2575076 TI - The origin of T cells in permanently reconstituted old athymic nude rats. Analysis using chromosome or allotype markers. AB - Athymic PVG-rnu/rnu rats receiving a single intravenous injection of syngeneic euthymic thoracic duct lymphocytes (TDL) develop normal levels of CD4+ T lymphocytes and survive for more than 2 years in a conventional animal house. We investigated the origin of the T cells (and B cells) in reconstituted nude recipients by transferring TDL carrying either the 3T chromosome marker or the RT6b + Igk-1b allotype or the RT7b (leucocyte-common) allotype markers. Karyotype analysis of spleen and lymph node (LN) cells from 1- to 2-year-old PVG-3T/3T reconstituted nude recipients, stimulated in vitro with phytohaemagglutinin (PHA), unexpectedly revealed that a majority (79-97%) of dividing cells were of nude origin. However, extensive nude cell division was also recorded in PHA stimulated cultures using mixtures of euthymic (PVG-3T/3T) and unreconstituted nude spleen cells; the assumption that only T cells divide in PHA-stimulated cultures thus appears to be erroneous. In contrast to the karyotype analysis, sIg RT6b+ LN cells obtained from nude recipients reconstituted 2 years earlier with PVG-RT6b allotype-marked TDL, were all of donor origin with no indication of a nude-derived sIg- RT6a+ population. Igk-1b+ donor B cells were not found in these same recipients. Dual fluorescence analysis of TDL from 18- to 20-month RT7b reconstituted nudes showed that 91-100% of CD4+ cells were donor-derived. When tested functionally, sIg- RT7b+ (donor) cells, but not sIg- RT7b- (nude-derived) cells, were able to reject skin allografts and induce local graft-versus-host (GVH) responses. Donor T cells, in contrast to CD4+ cells of nude origin, divided extensively in nude recipients; FACS-purified RT7b+ (donor) TDL retransferred from 17-month primary reconstituted nude rats, expanded further (60-100-fold) in secondary nude recipients. In conclusion, only the donor-derived CD4+ cells in reconstituted nude rats displayed T-cell function; evidence to the contrary from karyotype analysis was flawed. At no stage in their life did uninjected or T-cell reconstituted nude rats develop endogenous cells that in any way resembled CD4+ products of the thymus. PMID- 2575077 TI - Presence of a very small population of Thy-1+, L3T4+ cells producing large amounts of IL-3 in young athymic nude mice. AB - A mixture of phorbol myristate acetate (PMA) and ionomycin was found to stimulate spleen and lymph node cells (LNC) from 6 to 8 week-old-athymic BALB/c nude mice, as well as from control +/+ mice, to secrete interleukin-3 (IL-3) in vitro. The specificity of the IL-3 bioassay was attested to by the use of rabbit anti-IL-3 antibodies, and by the detection of an accumulation of IL-3 mRNA. Cytotoxic treatment with relevant antibodies showed that the cells responsible for the IL-3 production in athymic nude mice was Thy-1+, L3T4+, Ly2-, while both L3T4+ and Ly 2+ cells produced IL-3 in control +/+ mice. Although the levels of IL-3 secreted by nude LNC varied among experiments, nude LNC were able to produce IL-3 at a level comparable to or higher than +/+ LNC. In addition, nude LNC consistently secreted two to three times more granulocyte-macrophage colony-stimulating factor (GM-CSF) than +/+ LNC, and the majority of GM-CSF secretion was dependent on the presence of L3T4+ cells. In contrast, IL-2 production by nude LNC was markedly limited. Since the flow microfluorometry analysis failed to demonstrate the presence of L3T4+ cells (less than 1%) in nude LNC, compared with 40-50% L3T4+ cells in +/+ LNC, our results suggest that athymic nude mice have a small population of Thy-1+, L3T4+ cells characterized by its ability to secrete IL-3 and GM-CSF at a very high rate. PMID- 2575079 TI - Strain polymorphism in progression of aging: changes in CD4, CD8 bearing subpopulations. AB - Polymorphism of age-related changes in CD4 (L3T4) and CD8 (Lyt-2) determinants of spleen and thymus cells was assessed by fluorescence-activated flow cytometry. Cells from mice ranging from 5 weeks to greater than 2 years of age were examined. There is little age-related change in the proportion of CD4+ CD8- splenocytes in A, C57BL/6, DBA/1, DBA/2, and SJL mice (slopes 0.04, 0.06, 0.08, 0.17 and 0.17, respectively, when age in weeks was plotted against % of positive cells). Changes in the composition of the thymus are much more profound: CD4+ CD8+ cells of SJL mice decrease from 70% to less than 10% as the animals age from 5 to 69 weeks (slope -1.03), and in DBA/2 mice from 5 to 110 weeks (slope -0.88). While this decrease in CD4+ CD8+ cells occurs, there is a compensatory increase in CD4+ CD8- and CD4- CD8+ cells; this is a shift in the relative proportion of subpopulations rather than an increase in absolute cell numbers of a particular subpopulation. In contrast to the age-related changes of SJL and DBA/2 mice, there is relatively little change in the proportion of CD4+ CD8+ thymus cells in mice of strains C57BL/6, DBA/1 and A (slopes -0.03, -0.14 and -0.15, respectively). PMID- 2575078 TI - Cyclosporin A prevents the in vivo development of murine prothymocytes from uncommitted (Thy-1-) precursor cells. AB - Cyclosporin A (CsA) is known to cause atrophy of the thymic medulla in normal mice. We show that medullary regeneration in lethally irradiated animals reconstituted with syngeneic marrow is also inhibited. For such animals, thymic cortical development is apparently normal. However, if the marrow is depleted of either Thy-1+ or Lyt-1+ cells, thymic regeneration is severely inhibited by CsA. This is not a permanent process, since thymic regeneration proceeds normally if the drug is withdrawn. CsA is only effective at preventing thymic regeneration if it is given at the time of grafting; after a delay of 3 days it is ineffective. We conclude that CsA inhibits the development of prothymocytes (pre-T cells) from common stem cells in the marrow. The significance of these findings with reference to T-cell ontogeny and clinical bone marrow (BM) transplantation is discussed. PMID- 2575080 TI - Expression of Leu M1 antigen on a monoclonal B cell line established from a patient with rheumatoid arthritis. AB - The purpose of this study is to show that anti-Leu M1 antibody (anti-CD15), which has different staining characteristics in lymphoid and non-lymphoid cells, reacted against the surface antigen of a defined monoclonal B cell line. This antibody recognizes the sugar moiety, lacto-N-fucopentaose (LNF-III), which is linked to the cell membrane protein in several kinds of cells, but not in B cells. However, a human monoclonal B-cell line (TKS-1) which was established from the peripheral blood of a patient with rheumatoid arthritis, expressed the Leu M1 antigen spontaneously. The analysis of surface markers using a fluorescence activated cell sorter (FACS) has revealed that the surface markers of TKS-1 were anti-mu, delta, kappa, HLA-DR, DQ, Leu 12 (CD19) and Leu M1 (CD15). TKS-1 cells were not reactive with any of the following antibodies: anti-OK M1 (CD11b), Leu M2, Leu M3 (CD14), Leu M4, Leu 1 (CD5), Leu 2 (CD8), Leu 3 (CD4), Leu 4 (CD3), Leu 7 and Leu 11 (CD16). In addition, TKS-1 was positive to Epstein-Barr nuclear antigen, weakly positive to non-specific esterase without staining inhibition by NaF, and negative to peroxidase. TKS-1 cells produced IgM in the culture supernatant and have kappa-light chain rearrangement in its DNA. As shown in other studies, distribution of Leu M1 is very wide. This antigen is not a specific immunodiagnostic marker to distinguish the cell type. We conclude that it is possible to express Leu M1 antigen on the membrane of a B-cell lineage cell. PMID- 2575081 TI - Anaerobic infection of the lung and pleural space in tuberculosis. AB - Prevalence of anaerobic bacterial infection in 120 sputum positive cases of pleuro-pulmonary tuberculosis was found to be 53.3 per cent-either as pure or mixed with aerobes. Bacteroides fragilis and B. Melaninogenicus were isolated in 19 (26.6%) and 12 (18.72%) cases respectively. Sensitivity studies showed that these were most sensitive to metronidazole followed by rifampicin and kanamycin. The possibility of anaerobic infection may be considered in patients of pulmonary tuberculosis who do not respond to routine treatment. PMID- 2575082 TI - [Substitution for the tooth root by aquatic invertebrate skeleton from animal to man]. PMID- 2575083 TI - [Immediate filling of extraction sites in general practice: use of a resorbable biomaterial, natural coral]. PMID- 2575084 TI - The subcellular localization of the neu protein in human normal and neoplastic cells. AB - We have examined the subcellular localization of the neu protein by immunohistochemistry and immuno-electron microscopy, associated with immunoblotting of normal and neoplastic tissues with 2 monoclonal antibodies (MAbs). Immunoelectron microscopy clearly reveals that neu protein resides only on the lateral plasma membrane of the simple epithelium of the breast and on the plasma membrane of malignant breast cells. It is also found on the membranes of the microvilli and the apical vacuoles of the cells of the proximal convoluted tubule of the kidney. In the cytoplasm, the only immunoreactivity detected with both antibodies was on the membrane of the mitochondrial cristae of normal and malignant cells. Immunoblotting reveals that the molecular weight of the membrane protein is 185 and 155 kDa for the mitochondrial protein. The cell membrane staining pattern can be revealed by light microscopic immunohistochemistry only in malignant cells and is therefore specific for malignancy. The membrane expression in normal cells cannot be visualized in this way. The mitochondrial reactivity appears as a cytoplasmic granular staining when examined under the light microscope. Similar cytoplasmic staining has been described previously in other studies with other antibodies against the neu protein and has lead to speculation about its function in normal and malignant cells. However, it is demonstrated in this study that it is not the known neu-oncogene product. PMID- 2575085 TI - Prescribing patterns of neuroactive drugs in 98 schizophrenic patients. AB - Ninety-eight schizophrenic outpatients receiving pharmacotherapy were surveyed on two census days, 18 months apart. From this study sample it was found that, as recently as 1987, 18% of the patients were prescribed three classes of neuroactive drugs--16% two antipsychotic drugs simultaneously. Of antipsychotics receivers, 44% were prescribed anticholinergics, 3% antidepressants, and 4% benzodiazepines. Between census days, a significant shift from use of oral antipsychotics to the depot form of administration occurred, while polypharmacy frequency remained unchanged. An analysis of the data will provide guidelines for rendering a more rational pharmacological treatment. PMID- 2575086 TI - Lymphocyte proliferation in glutathione-depleted lymphocytes: direct relationship between glutathione availability and the proliferative response. AB - Lymphocyte proliferation in response to mitogenic lectins is directly dependent upon glutathione (GSH) availability. Thus, proliferation can be enhanced by providing lymphocytes with excess glutathione, and strongly inhibited by limiting the quantity of intracellular GSH available during the mitogenic stimulation. Exogenous GSH, cysteine and 2-mercaptoethanol (2-ME) can all significantly enhance lymphocyte proliferation and augment intracellular GSH levels. Lymphocytes depleted of GSH by buthionine sulfoximine (BSO) fail to undergo a full blast transformation response to mitogenic lectins. In lymphocytes stimulated with mitogen in the presence of BSO, the time profile of intracellular GSH levels shows a rapid decline over the first 24-48 h and a subsequent gradual decline to levels less than 0.5 nmol/10(7) lymphocytes by 72-96 h. Exogenous GSH partially sustains intracellular GSH levels and completely restores lymphocyte proliferation even in the presence of 2000 microM BSO. Other thiols, such as cysteine and 2-ME, do not significantly alter the time profile of intracellular GSH in mitogen-stimulated lymphocytes in the presence of 2000 microM BSO, and their capacity to enhance proliferation is greatly diminished albeit not completely abolished under these conditions. Ongoing GSH synthesis is clearly essential to maintain a normal proliferative response. If intracellular GSH levels are depleted initially and lymphocytes are then stimulated with mitogen in the presence of BSO, there is a diminished capacity of cysteine and 2-ME to restore proliferation relative to exogenous GSH. There is also a diminished capacity of exogenous GSH to restore proliferation with higher concentrations of BSO. This suggests that the restoration of lymphocyte proliferation by exogenous GSH is more closely linked to effects on intracellular rather than extracellular GSH. These studies confirm the importance of intracellular GSH in lymphocyte proliferation. The essential role for intracellular GSH can be demonstrated even in the presence of other exogenous thiols, such as cysteine and 2-ME. The enhancement of lymphocyte proliferation by exogenous cysteine appears to be directly linked to effects on intracellular GSH, whereas the enhancement by 2-ME is probably more complex but clearly linked to effects on intracellular GSH. PMID- 2575087 TI - [Heterogeneity of CD4+(helper)-T-cells: role in the pathophysiology of the skin]. AB - CD4+ cells play a central role in the immune system. Recent data show the existence of two distinct subsets of CD4+ cells in the peripheral blood of adults, which differ dramatically both in their functional capacities and in their surface phenotype. These two CD4+ subpopulations do not represent different lineages, but reflect sequential stages of maturation. As antigen contact causes transition to the subsequent subpopulation, these cells have been designated "naive" and "memory" T cells. It is remarkable that the quantitative relationship between the two subpopulations is very different within the skin from in peripheral blood: in inflammatory and in neoplastic CD4+ cutaneous infiltrates there is a predominance of memory T cells. Our own results show, furthermore, that this predominance of memory T cells is due to their selective emigration from the blood, most probably because of their high expression of several adhesion molecules. PMID- 2575088 TI - Evidence for the single origin of HB G-San Jose in Sicily. AB - Hb G-San Jose [alpha 2 beta 2 7(A4)Glu----Gly] was detected in four families and three unrelated individuals from Eastern Sicily. Polymorphic restriction sites within the beta-globin gene cluster bearing the mutation were characterized. A complete association of beta-G-San Jose alleles with Mediterranean haplotype IV was found in the families examined and the same haplotype was also present in the unrelated individuals. These findings support the hypothesis of an unicentric origin of the beta-G-San Jose mutation which may have arisen in Eastern Sicily. PMID- 2575089 TI - HLA-DQ mismatches between donor and recipient in the presence of HLA-DR compatibility do not influence the function or outcome of renal transplants. AB - Although matching of kidney donors and recipients for antigens of the HLA-DR series is considered to have a significant influence on graft outcome, the independent effects of incompatibilities for the closely linked HLA-DQ series of antigens are unknown largely because serological compatibility for HLA-DR usually ensures a corresponding compatibility for HLA-DQ. In a retrospective study using restriction fragment analysis we have identified clear HLA-DQ mismatches in 25 out of 62 recipients of HLA-DR-compatible kidney grafts. Though these incompatibilities correspond to differences at the cell surface and hence potential alloantigenic stimuli, none of the eight clinical parameters examined indicate that HLA-DQ mismatches in the presence of compatibility for HLA-DR have any significant effect on either graft function or outcome. PMID- 2575090 TI - The origin of HLA-DR"Br": exon 2 nucleotide sequence implicates possible gene conversion of DR1 by DR4-Dw10, DR5, or DRw6-Dw18. AB - The exon 2 nucleotide sequences of HLA-DQwl-associated and DQw3-associated HLA DR"Br" alleles were determined from genomic DNA amplified by the Taq polymerase chain reaction technique. Both alleles reveal identical exon 2 nucleotide sequences. Comparison with other DR alleles suggests that DR"Br" may have originated from DR1 by gene conversion with DR4-Dw10, DR5, or DRw6-Dw18 third hypervariable region sequences. PMID- 2575091 TI - Somatostatin potentiates cholinergic neurotransmission in ferret trachea. AB - We studied the effect of somatostatin on contractile responses to electrical field stimulation (EFS) in isolated ferret tracheal segments. Somatostatin (up to 10(-5) M) did not change resting tension, but it potentiated the contractile response to EFS dose dependently, with a maximum effect at 10(-6) M. Thus, at a concentration of 10(-6) M, somatostatin significantly decreased the mean log of EFS frequency producing 50% of maximum contraction from a control value of 0.52 +/- 0.07 to 0.24 +/- 0.06 (SE) Hz (P less than 0.01). The potentiating effect of somatostatin (10(-6) M) was not inhibited by hexamethonium, indomethacin, BW755C, pyrilamine, methysergide, or D,Pro2,D,Trp7,9-SP, but it was inhibited by atropine or by the somatostatin antagonist cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)]. In contrast to EFS-induced contraction, contractions produced by acetylcholine (10(-9) to 10(-3) M) were not affected by somatostatin at a concentration of 10( 6) M. These results suggest that somatostatin potentiates contractions produced by EFS via presynaptic cholinergic mechanisms and probably through a specific somatostatin receptor. PMID- 2575092 TI - Peroxisomal acetoacetyl-CoA thiolase and 3-ketoacyl-CoA thiolase from an n-alkane utilizing yeast, Candida tropicalis: purification and characterization. AB - Acetoacetyl-CoA thiolase (Thiolase I) and 3-ketoacyl-CoA thiolase (Thiolase III) found in peroxisomes of an n-alkane-utilizing yeast, Candida tropicalis pK 233, were each purified to homogeneity by successive column chromatographies. Thiolase I was composed of six identical subunits whose molecular masses were 41,000 Da, and Thiolase III was a homodimer composed of 43,000 Da subunits. The results of limited proteolysis of the respective thiolases indicated that they were quite different in peptide components. Furthermore, these enzymes were immunochemically distinguishable. The kinetic studies showed that the substrates with long chains were degraded exclusively by Thiolase III, while acetoacetyl-CoA was degraded preferentially by Thiolase I. Thus, in the yeast, the complete degradation of fatty acids is suggested to be carried out efficiently in peroxisomes. PMID- 2575093 TI - Enzymatic in situ analysis by 1H-NMR of the hydrogen transfer stereospecificity of NAD(P)+-dependent dehydrogenases. AB - We have established a simple procedure for the in situ analysis of stereospecificity of an NAD(P)-dependent dehydrogenase for C-4 hydrogen transfer of NAD(P)H by means of glutamate racemase [EC 5.1.13] and glutamate dehydrogenase [EC 1.4.1.3]. Glutamate racemase inherently catalyzes the exchange of alpha-H of glutamate with 2H during racemization in 2H2O. When the reactions of glutamate racemase and glutamate dehydrogenase, which is pro-S specific for the C4-H transfer of NAD(P)H, are coupled in 2H2O, [4S-2H]-NAD(P)H is exclusively produced. Therefore, if 1H is fully retained at C-4 of NAD(P)+ after incubation of a reaction mixture containing both the enzymes and a dehydrogenase to be tested, the stereospecificity of the dehydrogenase is the same as that of glutamate dehydrogenase. When the C4-H of NAD(P)+ is exchanged with 2H, the enzyme to be examined is different from glutamate dehydrogenase in stereospecificity. Thus, we can readily determine the stereospecificity by 1H-NMR measurement of NAD(P)+ without isolation of the coenzymes and products. PMID- 2575094 TI - Changes in the nuclear distribution of DNA polymerase alpha and PCNA/cyclin during the progress of the cell cycle, in a cell-free extract of Xenopus eggs. AB - The nuclear distribution of DNA polymerase alpha and PCNA/cyclin in embryonic nuclei has been investigated, in a cell-free extract of Xenopus eggs that recapitulates a basic cell-cycle in vitro, by indirect immunofluorescence microscopy. Both antigens co-distribute with the chromatin in S-phase nuclei; however, as DNA replication is completed and nuclei progress into a G2 state anti PCNA fluorescence disappears and anti-DNA polymerase alpha fluorescence becomes resolved into bright spots. These spots are initially associated with the chromatin strands and can be seen to share both anti-PCNA and anti-DNA polymerase alpha fluorescence, but as anti-PCNA fluorescence fades the spots become dissociated from the chromatin and are redistributed throughout the nucleus until they are dispersed during nuclear envelope breakdown. The loss of anti-PCNA fluorescence and displacement of anti-DNA polymerase alpha fluorescence from the chromatin can be prevented by inhibiting DNA synthesis with aphidicolin. Under these conditions both antigens remain associated with the chromatin even after nuclear envelope breakdown and lamin dispersal. The association of these antigens with mitotic figures appears to be functional, as both biotin-11-dUTP and [32P]dCTP can be incorporated efficiently into DNA during the mitotic period. PMID- 2575096 TI - Dental phobia. Conquering fear with trust. PMID- 2575097 TI - Biological abnormalities in late-life depression. PMID- 2575095 TI - Central angiotensin II stimulates arteriolar vasomotion in conscious hamsters. AB - The effects of intracerebroventricular (icv) injections of 10 ng angiotensin II (ANG II) on mean arteriolar diameter and spontaneous arteriolar vasomotion were studied in subcutaneous tissue of conscious, restrained hamsters, using the skin fold window chamber preparation. Angiotensin II caused a significant decrease in mean arteriolar diameter which was associated with a significant elevation in the amplitude of vasomotion. The frequency of vasomotion did not change significantly. The central ANG II-induced effects on arteriolar vasomotion were not significantly altered by continuous intravenous (iv) infusion of hexamethonium (1 mg.kg-1.min-1). In contrast, iv bolus injection of the vascular vasopressin receptor antagonist d(CH2)5Tyr(Me)AVP (10 micrograms.kg-1) 5 min prior to icv injection of ANG II significantly attenuated the effects of the neuropeptide on mean arteriolar diameter and the amplitude of vasomotion. These data indicate that central ANG II stimulation enhances arteriolar vasomotion in peripheral subcutaneous tissue of conscious hamsters and that this effect may be mediated by release of vasopressin. PMID- 2575098 TI - A short term open clinical trial of clobazam in the treatment of patients with panic attacks. AB - Clobazam, a 1-5 benzodiazepine with anxiolytic properties, was evaluated in the treatment of patients with DSM-III panic disorder or agoraphobia with panic attacks. In this open clinical trial, 10 of the 15 patients completed 8 weeks of treatment. Six of the 10 completers (60%) were responders (75% reduction in the number of panic attacks from baseline) at the end of 8 weeks. Of the responders so defined, 5 of the 6 were panic free. At the end of week 8 the average dose for the responders to medication was 50 +/- 17 (S.D.) mg per day. Clobazam was well tolerated at the doses used with the few side-effects recorded as mild to moderate. The study suggests that further placebo-controlled studies are warranted to evaluate clobazam's potential antipanic effect. PMID- 2575099 TI - Evaluation of three methods for culturing long intravascular catheters. AB - During a one-year period, 236 intravascular catheter tips were investigated by culturing the outside by rolling the tips on the surface of blood agar plates, the inside by flushing with nutrient broth, and finally by culture after ultrasonication. Clinical information was collected prospectively by visiting the ward and symptoms and signs of catheter infection were correlated with the results of the catheter cultures. Coagulase-negative staphylococci were the organisms that were most frequently isolated from the catheters. The results of culture showed a clear bimodal distribution, and counts of 100 colony-forming units (cfus) and culture from the inside of the catheters were the best predictors of infection. Almost all infected catheters were colonized both on the inside and outside. PMID- 2575100 TI - Effects of heparin and chlorbutol on bacterial colonisation of intravascular cannulae in an in vitro model. AB - An in vitro model was used to study the effects of heparinised saline, with or without the preservative chlorbutol, on the colonisation of intravascular cannulae. Chlorbutol significantly reduced cannula colonisation by Staphylococcus epidermidis. Flushing colonised cannulae with heparinised saline plus chlorbutol significantly reduced the number of organisms adhering to the inner surface of cannulae, when compared with the use of heparinised saline without preservative. Chlorbutol-preserved heparinised saline may not only maintain cannula patency by the prevention of thrombus formation, but may also reduce the incidence of bacterial colonisation of cannulae in vivo. PMID- 2575102 TI - Infectious complications during therapy of acute leukaemia in Saudi Arabia. AB - In 40 febrile neutropenic episodes during the induction and consolidation chemotherapy of acute leukaemia in Riyadh, 51% of organisms causing septicaemia were gram-negative, 26% gram-positive, 8% anaerobes and 15% fungi. In 21 (52%) febrile episodes there were pulmonary infiltrates; of the 12 where aetiology was known, six were due to fungi. Pulmonary infiltrates progressed to adult respiratory distress syndrome and death in nine instances. There was no significant occurrence of parasitic and tropical infections. The results show that the pattern of infection, during therapy of acute leukaemia in developing countries, may have important differences when compared with western centres. Empiric amphotericin B may need to be introduced at an earlier stage in patients with persistent fever or progressive pulmonary infiltrates. PMID- 2575101 TI - Nosocomial bacteraemia in a teaching hospital in Saudi Arabia. AB - During a period of one year, 117 episodes of nosocomial bacteraemia were documented at King Khalid University Hospital, an incidence of 5 per 1000 admissions. Sixty-two percent were gram-negative organisms with Escherichia coli, Klebsiella spp., Serratia spp. and Pseudomonas spp. being the most frequent. Staphylococcus aureus was the most common gram-positive organism isolated. The source of infection was identified in 75% of patients. Intravenous lines accounted for a high proportion of cases (22%). Most deaths occurred in infants and patients with serious underlying disease. PMID- 2575103 TI - Nosocomial gram-negative bloodstream isolates: a comparison of in vitro antibiotic potency. AB - Nosocomial bloodstream infections add to the morbidity, mortality and length of hospitalization that is attributed to the underlying diseases alone. We have compared the in vitro potency of fifteen antibiotics against 136 isolates from clinically significant nosocomial gram-negative bacteraemias. Ciprofloxacin was the most potent antibiotic and had the broadest spectrum of activity (98% of isolates susceptible, MIC90 range: 0.06-0.5 micrograms ml-1). We subjected all isolates to beta-lactamase induction but antibiotic susceptibility was unaffected by this procedure. PMID- 2575104 TI - Hepatitis B screening in a northern Irish mental handicap institution: relevance to hepatitis B vaccination. AB - The current DHSS guidelines on immunisation against hepatitis B in mental handicap hospitals recommend vaccination for personnel at risk directly involved in patient care (who may have direct contact with patients or their body fluids) and for new admissions into institutions where the incidence is known to be high. We report a serological survey of hepatitis B markers in over 99% of the residents of a large mental handicap hospital. Of 720 patients tested only one carried hepatitis surface antigen. This patient was anti-HBe positive. Only 4.5% of the residents carried any hepatitis marker. These results do not suggest the need for a local vaccination programme for patients or staff. PMID- 2575105 TI - Epidemic iatrogenic Acinetobacter spp. meningitis following administration of intrathecal methotrexate. AB - We report the first outbreak of Acinetobacter species meningitis in a group of children with acute leukaemia following the administration of intrathecal chemotherapy. Eight of twenty patients receiving methotrexate injections on a single day developed signs and symptoms of meningitis within 18 h of treatment, and cases were clustered by time of administration. A cohort study comparing case and non-case patients did not identify any specific host factor associated with meningitis. Acinetobacter calcoaceticus var anitratus was isolated from the cerebrospinal fluid (CSF) of five patients; three patients died. Our investigation determined that the methotrexate was extrinsically contaminated by reused needles, used for reconstitution and administration, which had been inadequately sterilized. Acinetobacter calcoaceticus var anitratus was isolated from an autoclaved needle and a vial of methotrexate used for chemotherapy; these and the clinical isolates had similar antibiograms. After introduction of single use disposable needles no subsequent cases occurred. PMID- 2575106 TI - Application of the hygienic hand-disinfection test to the gloved hand. AB - The Austrian Standard Hygienic Hand-Disinfection Test was adapted for comparing the effect of washing artificially contaminated hands (using Escherichia coli) with contaminated gloved hands, using liquid soap and rinsing with water. Tests showed that a single soap wash completely removed all the bacteria from the glove, and was more than 1000 times more effective on the glove than on the hand. PMID- 2575107 TI - The effect of air with steam on the temperature of autoclave contents. AB - The effect of residual air on the local temperature within an autoclave has often been calculated solely from the known relationship between the pressure and temperature of steam in equilibrium with water. A system of directly measuring air is described which, together with temperature measurements, indicates that large volumes of air trapped in an autoclave load are not necessarily associated with reduced temperatures, although their presence will considerably prolong the heat-up period. It is confirmed that a restricted flow of steam into an autoclave chamber, with reliance on a 'balanced pressure' thermostatic trap as a condensate and air outlet, will not remove air efficiently, even from an empty chamber. Long heating times observed when polypropylene containers are used for laboratory discard material are probably due to retention in the container of large volumes of air. When an efficient air displacement system is employed heat-up times are considerably reduced; the conductivity of the container material being less important than the penetration of steam to its contents. PMID- 2575108 TI - Definition of amputation wound sepsis. PMID- 2575109 TI - Magnesium and chlorhexidine MIC determination. PMID- 2575110 TI - An unexpected cause of pseudobacteraemia. PMID- 2575111 TI - Rhabdomyolysis and acute renal failure associated with Salmonella enteritidis infection. PMID- 2575112 TI - Serious infections with Streptococcus agalactiae in adults: how often is it a nosocomial infection? PMID- 2575113 TI - An outbreak of Klebsiella pneumoniae bacteraemia in five children on intravenous therapy. PMID- 2575114 TI - Restriction fragment length polymorphisms mapped in spontaneously hypertensive rats using kallikrein probes. AB - We have explored the role of kallikrein-kinin system in essential hypertension using spontaneously hypertensive rats (SHR) as an animal model. A rat tissue kallikrein complementary (c) DNA (RSK 1105) was used as a probe in Southern blot hybridization to detect restriction fragment length polymorphisms (RFLPs) in SHR. Using 23 different restriction endonucleases, we have identified five RFLPs involving alterations in restriction fragment lengths for the restriction enzymes Bgl II, Dra I, Nde I, Sph I, and Bcl I. Three of the enzymes, Nde I, Sph I, and Bgl II, generate multiple polymorphic fragments. We have further mapped these RFLPs with two additional probes, both from the rat renal kallikrein gene RSKG 7. The 5' probe, consisting of sequences approximately 2000 base pair (bp) 5' of the first exon, recognizes RFLPs in DNA digested with Bcl I and Sph I. The 3' probe, approximately 4400 bp away from the fifth exon, recognizes polymorphic fragments in DNA digested with Bcl I, Dra I and Nde I. These findings indicate possible differences in tissue kallikrein genes or their regulatory regions in SHR that could contribute to the pathogenesis of hypertension in this animal model. PMID- 2575115 TI - Decrease in alpha 1-adrenoceptor reserve in mesenteric arteries isolated from spontaneously hypertensive rats. AB - The characterization of alpha-adrenoceptor-mediated contractile responses and the effects of the calcium channel blocker nifedipine on these responses were investigated in mesenteric arterial strips from 13-week-old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Contractile responses to the alpha-adrenoceptor agonists phenylephrine and clonidine were mediated through the activation of alpha 1-adrenoceptors. The dose producing a half-maximum response (ED50) for the agonists was higher in SHR than in WKY. Affinities of alpha 1-adrenoceptors were similar between the two strains. When arterial strips from both strains were treated with the same concentration of phenoxybenzamine, the maximum response to each agonist was weaker in SHR. The alpha 1-adrenoceptor occupancy-response relationship for phenylephrine was hyperbolic and less steep in SHR, while the relationship for clonidine was linear in SHR but not in WKY. Alpha 1-adrenoceptor occupancy at a half-maximum response to each agonist was greater in SHR. Nifedipine inhibited the maximum responses to the agonists more profoundly in SHR than in WKY. This inhibition was greater in the response to clonidine than in the response to phenylephrine in both strains. When the maximum response to phenylephrine was reduced to the same extent in both strains by treatment with different concentrations of phenoxybenzamine, the responses to phenylephrine were more susceptible to inhibition by nifedipine. Under these conditions, the effects of nifedipine were similar between SHR and WKY. These results suggest that alpha 1-adrenoceptor reserve is reduced in SHR mesenteric artery compared with WKY, which may be responsible for the greater inhibition by nifedipine of the alpha 1-adrenoceptor-mediated contractions in SHR. PMID- 2575116 TI - Comparison of monocyte separation methods using flow cytometric analysis. AB - We isolated normal, nonactivated human monocytes from peripheral blood by four different methods: (1) rosetting with sheep erythrocytes pretreated with 2 aminoethylisothiouronium bromide hydrobromide (AET) followed by monoclonal antibody (OKT3 (CD3), B1 (CD19), Leu7, Leu11 (CD16] and complement treatment; (2) adherence to gelatin/plasma-coated flasks; (3) adherence to plastic dishes; and (4) separation by the Sepracell technique. We monitored these monocyte separations by determining cell recoveries, OKT4A+ lymphocyte contamination, monocyte binding to human immunodeficiency virus (HIV), number of non-specific esterase-positive cells, and proportion of mononuclear cells reactive with a battery of monoclonal antibodies specific for monocytes. Our results indicate that of the four methods compared, adherence to gelatin/plasma-coated flasks produced the highest purity, recovery, and satisfactory binding to HIV with the fewest contaminating CD4+ T cells. PMID- 2575118 TI - Function of the avian cecum. Proceedings of the First International Avian Cecal Symposium. Grand Marais, Minnesota, August 21-26, 1988. PMID- 2575117 TI - [Dipeptidyl aminopeptidase IV in hospitalized patients and in galactosamine hepatitis of the rat: Activity and lectin affinity chromatography in serum and hepatic plasma membranes]. AB - The activity of dipeptidyl aminopeptidase IV was studied in the sera of 378 hospitalized patients. The mean activity of dipeptidyl aminopeptidase IV was elevated significantly in patients with neoplasmata and hepatitis, but not in patients with liver cirrhosis. Significant correlations (p less than 0.001) existed with gamma-glutamyl transferase, glutamate dehydrogenase, alkaline phosphatase and leucine aminopeptidase. A significant correlation with lactate dehydrogenase existed only in patients with neoplasmata. Principal component analysis, performed with aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, leucine aminopeptidase, lactate dehydrogenase and dipeptidyl aminopeptidase IV, revealed correlations between the activities of aspartate aminotransferase and alanine aminotransferase, and between alkaline phosphatase and leucine aminopeptidase, but neither dipeptidyl aminopeptidase IV nor lactate dehydrogenase showed any correlation with either of these two groups. In lectin affinity chromatography with concanavalin A and wheat germ lectin sepharose, serum dipeptidyl aminopeptidase IV from liver cirrhosis patients showed the same binding pattern as that from healthy subjects. The activity and glycosylation of dipeptidyl aminopeptidase IV in serum and hepatic plasma membranes was investigated in rats, following the induction of hepatitis with galactosamine. In the serum, dipeptidyl aminopeptidase IV activity was elevated as early as 6 h after galactosamine injection, and the elevated activity persisted until the 7th day. At the same time dipeptidyl aminopeptidase IV activity was also elevated in the hepatic plasma membrane. Ninety eight percent of hepatic dipeptidyl aminopeptidase IV bound to concanavalin A as well as to wheat germ lectin and this value was unchanged during hepatitis. In the serum of control rats, 90% of dipeptidyl aminopeptidase IV bound to concanavalin A but only 39% to wheat germ lectin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575119 TI - Avian cecal microanatomy: a morphometric comparison of two species. AB - Tissues from the proximal, middle, and distal regions of the ceca of Gambel's quail and domestic fowl were examined by scanning and transmission electron microscopy for ultrastructural detail. Cellular aad subcellular structures, including epithelial cell height, mitochondrial volume fraction, microvillar surface area, and junctional complex characteristics, were quantified by stereologic procedures. The mucosal surface of the quail ceca shows a more highly developed pattern of ridges and flat areas than that of the fowl. The fowl has significantly greater cell heights than the quail in all cecal regions. The mitochondrial volume fraction does not differ significantly with species or region, but the mitochondria in all samples tend to be concentrated on the apical side of the nucleus. In both species, the proximal cecal region has the greatest microvillar surface area. In the fowl cecum, the zona occludens and macula adherans heights are significantly less in the proximal than in the middle or distal regions. In the quail cecum, the zona adherans height is least is the distal region. The zona occludens height in the fowl middle and distal regions is significantly greater than those for the quail. The middle region of the quail cecum has the lowest proportions of cell boundaries with zona adherans and macula adherans in the junctional complexes. When all factors are considered, the quail ceca appear to have morphological characteristics consistent with a greater potential capacity for absorption by passive diffusion than the fowl ceca. PMID- 2575120 TI - Absorption by the cecum of wild birds: is there interspecific variation. AB - The major functions proposed for the avian cecum--energy balance and osmoregulation--involve absorption of material from the cecum, yet little is known of these absorptive processes in wild birds. The magnitude of transport of compounds from the ceca depends on the concentrations of compounds in the ceca, the presence of transport pathways for those compounds, and the size of the reabsorptive surface. Interspecific variation in size of avian ceca is well documented, but the other two determinants of absorption are much less well studied. All ceca examined contained acetic, propionic, and butyric acid; water content varies from less than 70 to greater than 90%. Most other constituents have been quantified in just one or two species. A model for cecal transport, derived from studies of mammalian ceca but consistent with observations on birds, is described. A luminal (mucosal) Na+/H+ exchanger couples the absorption of Na+ to that of volatile fatty acids, which are absorbed in their uncharged (protonated) form; these two compounds are thereby mutually stimulatory in their absorption. The cecum also absorbs water, sodium, carbon dioxide, and probably some nitrogenous compounds (e.g., ammonia). Too few data exist to analyze interspecific variation in cecal transport in birds. However, variations in the following characteristics do exist: cecal contents, cecal absorptive surface area, transport characteristics of other regions of avian intestine (e.g., rectum), cecal transport among mammalian species, and histology of avian ceca. Studies of the physiological consequences of these variation should yield insight into the function and contributions of the avian cecum. PMID- 2575121 TI - Sugar and amino acid transport properties of the chicken ceca. AB - Chickens have two well-developed ceca, with an epithelium that is histologically and functionally heterogeneous. The proximal region, close to the ileorectal junction, has well-developed villi and microvilli and is able to transport sugars and amino acids against a concentration gradient, by mechanisms virtually identical to those described for the small intestine. The medial-distal region does not have true villi but has mounds and ridges, and it cannot transport either sugars or amino acids in the adult bird. In newborn chicks, the whole cecum can accumulate and transport sugars, but this property is soon restricted to the proximal region. The medial cecum, however, retains some transport capacity until the 8th week after the hatch. Ceca are thus well suited for sugar and amino acid absorption. Their contribution to the overall nutrient absorption is, however, limited, because the absorbing epithelium is exposed to the intestinal contents only during the filling and emptying of the cecal segments. PMID- 2575122 TI - Interspecific variation in sugar and amino acid transport by the avian cecum. AB - Previous studies of cecal sugar and amino acid transport in the domestic chicken led to a widely held generalization that the avian cecum is unimportant as a site of nutrient transport. In fact, we found that the uptake capacity of the cecum for hexose sugars and amino acids is substantial in some species of birds. Cecal transport of glucose was measurable in all five study species (Canada goose, sage grouse, domestic chicken, red-necked phalarope, and rock dove), approached or exceeded intestinal levels in the grouse and phalarope, and accounted for between 0.1% (rock dove) and 49% (sage grouse) of the whole gut's integrated uptake capacity. Proline uptake averaged higher in the proximal portion of the cecum than in any region of the small intestine for all species but the goose. The ceca contributed between 2% (rock dove) and 25% (sage grouse) of the gut's integrated uptake capacity for proline. Similar ranges were found for fructose, lysine, leucine, and aspartate. Future studies should be undertaken to search for phylogenetic and ecological correlates of the interspecific variation in cecal transport and to determine how nutrient transport integrates with other functions of the avian cecum. PMID- 2575123 TI - Anatomy of the avian cecum. AB - The gross anatomy of the avian ceca is reviewed. In most birds, right and left ceca arise laterally or ventrolaterally at the junction of the small and large intestines. In a few species, the ceca open into the rectum ventrally or dorsally. In many herons and bitterns, only one cecum is present, and in the secretary bird there are two pairs of ceca. Ceca are absent in woodpeckers, hummingbirds, swifts, kingfishers, pigeons, mousebirds, cuckoos, and parrots. Ceca may be classified according to length into long, moderately or poorly developed, and vestigial types. In most birds, the ceca are simple tubular structures with minor variations in shape. However, in a few species, including the ostrich, rheas, kiwis, some tinamous, the red-throated loon, screamers, the satyr tragopan, the great bustard, and the pin-tailed sandgrouse, the ceca are sacculated or have diverticula. There is usually no correlation between the development of the ceca and systematic position. Except in grouse (Tetraonidae), in which the long ceca are related to the fibre content of the diet, the correlation between cecal development and diet is extremely limited. There is no relationship between the size of the ceca and the length and width of the rectum. PMID- 2575124 TI - Ultrastructural differences between the two major components of chicken ceca. AB - The central parts of basis and corpus ceci from White Plymouth Rock hens on different salt regimen were investigated by light, scanning electron, and transmission electron microscopy. The mucosal surface varies from long broad, flat villi in basis to blunt rugae in corpus ceci. In the epithelium of basis ceci there are many goblet cells, whereas in corpus ceci they are few in number and predominantly located in the crypts and sides of rugae. The microvilli of basis ceci are longer than those of corpus ceci. The epithelium from corpus ceci contains apically located cytoplasmic inclusions of microtubular-like aggregations. The size and amount of these inclusions decrease towards the crypt openings, and none were observed in crypt epithelium. The mitochondria in the epithelium from basis ceci are seen close to the apical plasma membrane, but in corpus ceci they first appear deeper in the cytoplasm below the apical vesicles, microtubular-like aggregations, and lysosomes. The size and content of the apical vesicles varies between the two compartments, as do deposits of lipoglycoproteins in the intercellular space and vesicles of the lateral plasma membrane. Several differences were thus revealed between the epithelia from basis and corpus ceci, giving morphological evidence for different functions between the two compartments. There were no effects of the two salt diets on the development of microvilli, whereas some cytological differences, such as the degree of microtubular-like aggregations, were seen in corpus ceci. PMID- 2575125 TI - Transport of water and food particles through the avian ceca and colon. PMID- 2575127 TI - Microbes of the avian cecum: types present and substrates utilized. AB - This paper discusses the types and properties of microorganisms found in avian ceca, with special reference to the chicken. Microbial activity in the cecum is primarily fermentative, but there has been little evidence of cellulose fermentation, and the predominant bacterial types are relatively inactive against other high-molecular-weight compounds of dietary origin. In all avian species examined, the consistent presence of large populations of uric acid-degrading bacteria supports the view that microbial populations in the ceca permit reabsorption of water and possibly nonprotein nitrogen from the backflow of urine. These capabilities may be of particular importance to wild birds under conditions of water and food deprivation. PMID- 2575126 TI - Relationship of cecal and colonic motility to diet, habitat, and cecal anatomy in several avian species. AB - Previous studies have described several types of contactile activity in the ceca and colon of turkeys. Cecal contractions were termed major and minor; major were propulsive, and minor were presumed to be mixing contractions. Both types propagated either orad or aborad. Colonic contractions were termed long-duration and short-duration, with both types being propulsive. Long-duration contractions were directed aborad; short-duration were directed orad, i.e., antiperistaltic. The latter are believed to be responsible for filling of the ceca from colonic contents and for urinary reflux through the colon. Of eight wild species examined radiographically, there appeared to be little relationship between the cecal size, the nature of colonic antiperistalsis, the type of diet, or the availability of water in the habitat for each species. PMID- 2575128 TI - Hindgut fermentations in nonavian species. AB - A brief comparative discussion of the hindgut of insects, mammals, fishes, and reptiles includes morphology of the hindgut, general appearance, content, materials fermented, fermentation products, microorganisms involved, and value of the hindgut to the host animal. The problems faced by small animals in securing adequate energy from a hindgut fermentation to be of value to the animal are presented. It is suggested that our present analytical methods are not adequate and that new approaches to analyzing the hindgut fermentation value should be investigated, such as using fecal bacterial mass as an index. It is also suggested that experimental and commercial feeding should be designed so that herbivores are not converted to omnivores. PMID- 2575129 TI - Gut size and the digestion of fibrous diets by tetraonid birds. AB - A series of diets containing different proportions of heather was fed to red grouse. Heather is the bird's main natural food and contains much fiber; the rest of each diet was a relatively low-fiber, grain-based formulation. With increasing heather and associated fiber contents, food intake increased and overall digestibility of heather was only 9.4%, but, when heather was eaten as the sole food by wild red grouse, its digestibility was 46%. Adaptations to diets containing more heather included increases in the size of the digestive system. Gizzard weight increased linearly with food intake. Lengths of intestines and particularly ceca also increased with intake, but not linearly. Up to an intake of about 50 g dry matter/day no significant change occurred. Above 50 g/day, gut size increased rapidly. Bulk may have started to limit intake at about 50 g/day. One can think of galliform digestion functioning in two modes: 1) a low-fiber mode, in which bulk does not limit intake and fiber digestion is unimportant; and 2) a high-fiber mode, in which bulk limits intake and fiber digestion may well be important. Most studies on avian digestion have been of captive galliforms, most of which probably function in low-fiber mode all the time. Wild galliforms seem to function in high-fiber mode for much of the time, but this has been studied little. PMID- 2575130 TI - The avian ceca: obligate combustion chambers or facultative afterburners? The conditioning influence of diet. AB - Changes in the anatomy and microbiology of the gut of many galliforme birds are influenced by the amount of crude fiber in the diet; the response is biphasic. As crude fiber in the diet increases, the bird compensates for the dilution of dietary energy content by increasing the amount it eats, which causes an increase in gizzard size. After exceeding a threshold in fiber content, where the metabolizable energy intake is limited by the sheer bulk of the food consumed relative to the ability of the bird to ingest food, there is an increase in hindgut size and a change in the microflora that allows extraction of energy from cellulose through the production of volatile fatty acids (VFAs). The result is a change in the apparent digestibility of the diet. Altering the energy demands through the application of environmental stressors, such as lowered temperature, may alter a hypothalamic or other regulatory mechanism setpoint at which hindgut hypertrophy occurs. The time frame required for such changes is between 4 and 8 weeks. Studies to determine digestibility of nutrients or the response of the gut of birds to altered diets must allow a sufficient period of time for gut adaptation prior to assessing its function. Other factors, such as age, photoperiod, and environmental factors, may affect the response of the gut. PMID- 2575131 TI - Uric acid decomposition in the lower gastrointestinal tract. AB - Uric acid is the end product of nitrogen metabolism in birds. Despite the very low aqueous solubility of this purine compound, few crystals of uric acid are found in the urine. Instead, uric acid is packaged into small spheres that can pass easily through the duct system of the kidney. After entering the cloaca, these spheres are moved with the urine by antiperistalsis into the rectum and digestive ceca. In the ceca, the uric acid is exposed to a large population of bacteria that can use the uric acid as a metabolic substrate. These bacteria degrade the uric acid to volatile fatty acids (VFA) and ammonia. The VFA are absorbed by the cecal tissue, and the ammonia is incorporated into the production of glutamine. The refluxing of uric acid into the ceca and its subsequent degradation by bacteria provides an effective mechanism for the reclamation of carbon and nitrogen from the urine. PMID- 2575132 TI - Ammonia production from uric acid, urea, and amino acids and its absorption from the ceca of the cockerel. AB - Experiments were conducted in situ and in vitro in the ceca to measure ammonia production from uric acid, urea, and amino acids and its absorption. When uric acid was injected into a cecal sac containing mixed cecal microfloras, 77% disappeared within 1 hour, with a concomitant increase in ammonia concentration. When [15N]uric acid was added to the ceca in situ, 28% was converted to ammonia after 30 minutes. About 92% of the ammonia introduced into a cecal sac disappeared from the lumen fluid within 30 minutes. About 43% of each of urea nitrogen and glutamine-amide nitrogen was converted to ammonia-nitrogen, and 25% of uric acid-nitrogen and epsilon nitrogen of the arginine was found in ammonia. The conversion of aminonitrogen of glutamic acid and glycine to ammonia amounted to 19-20%, whereas that of alpha-alanine totaled 11%. It is concluded that dietary and urinary nitrogenous compounds that find their way into the ceca are useful nitrogen sources for ammonia production by microflora in the ceca of the chicken, and that ammonia is absorbed rapidly from the ceca. PMID- 2575133 TI - Effect of cecectomy on water and nutrient absorption of birds. AB - The effect of the removal of the avian digestive ceca on osmoregulation and on absorption of certain nutrients is reviewed. While data indicate that the ceca have the potential for absorption of a significant quantity of water, several studies have demonstrated that effects of cecectomy on water intake and output are transitory and that compensatory adjustments made within 2 to 3 weeks postsurgery allow cecectomized birds to eat and gain weight normally. However, cecectomized great horned owls exposed to 27 degrees C turned over their body water 1.6 times faster than intact owls under the same conditions, suggesting that the ceca do have a vital role in water balance of thermally stressed horned owls. Cecectomy resulted in slightly lower metabolizability of food, lower digestibility of crude fiber in low fiber diets, and greater loss of certain amino acids in cecectomized birds that were fasted or fed a protein-free diet. The latter suggests that the ceca are important in recovery of amino acids endogenous protein degradation. Loss of cecal function also resulted in higher energy intake and excretion in Japanese quail, amounting to 5.7% of the total daily energy requirement. PMID- 2575134 TI - Why do grouse have ceca? A test of the fiber digestion theory. AB - Two predictions deduced from the theory that grouse ceca function primarily to provide a suitable environment for the fermentation of plant fiber were tested. Digestion of neutral detergent fiber in conifer needles by blue grouse (Dendragapus obscurus) varied from 7.5 to 17.3% across tree species, but, contrary to prediction, the energy potentially derivable from this fiber digestion was insufficient to make ceca energetically profitable. Variation in digestibility of fiber among birds and across species was caused by differential accessibility of fiber to the ceca as essentially all (average, 96.8%) fiber entering the ceca was digested. An allometric analysis of grouse gut lengths suggested, and a correlation analysis confirmed, that cecal lengths among species of grouse decrease in length as dietary fiber increases, also soluble and suspended particulate food components from insoluble. Ceca do act as fermentative and absorptive reservoirs for fiber, but also (and predominantly) for urine and cell soluble or suspended components previously undigested because of high rates of passage. I suggest that the adaptive significance of this strategy is to maximize the rate at which energy is obtained from poor quality foods. PMID- 2575135 TI - Water and electrolyte transport by the avian ceca. AB - In galliform birds with well developed ceca, these are functionally important components of the lower intestinal complex, which is capable as a whole of substantial, hormone-regulated homeostatic modification of mixed urine and intestinal luminal fluid before final excretion. Active Na+ transport drives Na linked absorption of water and Cl- and secretion of K+; there are also lesser Na independent components of the latter fluxes. These transport processes are appropriately enhanced by dehydration, Na depletion, or exogenous aldosterone. PMID- 2575136 TI - Mechanism of recovery from acute virus infection. IX. Clearance of lymphocytic choriomeningitis (LCM) virus from the feet of mice undergoing LCM virus-specific delayed-type hypersensitivity reaction. AB - As shown previously, after inoculation into the footpad of a mouse the lymphocytic choriomeningitis (LMC) virus multiplies locally. Beginning on day 6 or 7 after infection, the foot undergoes a delayed-type hypersensitivity (DTH) reaction which consists of two distinct phases that are mediated by CD8+ cells and CD4+ cells, respectively, and at about the same time the virus is eliminated. In general, for terminating infection of the mouse with LCM virus the CD8+ cytotoxic/suppressive T lymphocyte (CTL) is essential; we have now determined the cells that mediate control of the virus in a tissue undergoing a specific DTH reaction. Depletion, in infected mice, of all T lymphocytes by treatment with anti-Thy-1 monoclonal antibody prevented virus elimination from the foot, and the same was true when the CD8+ CTLs were removed. Depletion of the CD4+ helper/suppressor subset only marginally impaired the ability of the mice to rid themselves of the virus. The conclusion that here too the principal antiviral element is the CD8+ CTL was confirmed by experiments in which footpad-infected mice were adoptively immunized with virus-immune splenocytes from syngeneic mice selected for subclasses of T lymphocytes, or from mice differing in defined regions of the major histocompatibility complex (MHC), and also by experiments in which monocytes were virtually absent. However, CD8+ CTL alone or cells from MHC recombinant mice with identity in class I loci were never as antivirally active as unseparated splenocytes from syngeneic donor mice. Since the CD8+ cells' performance could be optimized by interleukin-2, we assume that the CD4+ T lymphocytes function as accessory cells; the same probably applies to monocytes. PMID- 2575137 TI - Evaluation of human and simian immunodeficiency virus plaque and neutralization assays. AB - A number of CD4+ T cell lines were compared for their ability to act as target cells for human immunodeficiency virus (HIV) infection in syncytium- and plaque forming assays. MT-4 and C8166 cells were the most sensitive indicator cells for HIV- and simian immunodeficiency virus (SIV)-induced cytopathic effects, and gave rise to macroscopic (MT-4) and microscopic (C8166) plaques. The MT-4 plaque assay was evaluated for the measurement of HIV- and SIV-neutralizing antibodies. PMID- 2575138 TI - Organ distribution of proteinase-resistant prion protein in humans and mice with Creutzfeldt-Jakob disease. AB - We attempted to clarify the organ distribution of human and murine proteinase resistant prion protein (PrPCJD) in Creutzfeldt-Jakob disease (CJD), and to measure the concentration of PrPCJD, using a semi-quantitative Western blot analysis. Human PrPCJD was restricted to the central nervous system, whereas murine PrPCJD was present in the central nervous system and in the lymphoreticular system at the end stage of CJD. PrPCJD concentration in the central nervous system of mice was almost identical to that of humans. The minimum wet weight of an organ with a positive reaction was 0.3 mg for brain, 1 to 3 mg for spleen, 3 mg for spinal cord, 3 mg for lymph node, 10 mg for thymus and 10 to 30 mg for intestine of the CJD-infected mice. There were no immunoreactions in purified PrPCJD fractions from 300 mg of spleen, lymph node, liver or peripheral nervous systems of humans, nor in 300 mg of liver, lung or kidney of CJD-infected mice. Within the limits of our method, the distribution of murine PrPCJD differed from that of human PrPCJD. Antibodies on the Western blot membrane from murine spleen PrPCJD fractions stained the kuru plaques in the CJD infected mouse brain. Therefore, PrPCJD in the murine spleen probably shares the epitopes of the antigen in the murine kuru plaques. Although the immunological detection of PrPCJD does have limits of sensitivity, PrPCJD concentrations did correlate with infectivity titres in scrapie-infected or CJD-infected mice. PMID- 2575139 TI - A new spermatostatic glycoside from the soft coral Sinularia crispa. AB - The steroid glycoside 1 has been isolated from the Sri Lankan soft coral Sinularia crispa. The structure has been determined by spectroscopic (1H and 13C nmr) techniques. Glycoside 1 showed spermatostatic activity on rat cauda epididymal spermatozoa. PMID- 2575140 TI - Summary of the 1989 EPA/A&WMA International symposium: measurement of toxic and related air pollutants. AB - A joint conference, for the fourth straight year cosponsored by the Air & Waste Management Association's TP-6, TP-7, and ITF-2 technical committees, and the Atmospheric Research and Exposure Assessment Laboratory of the U.S. Environmental Protection Agency, was held at Raleigh, North Carolina, May 2-5, 1989. The technical program consisted of 145 presentations, held in 14 separate technical sessions, on recent advances in the measurement and monitoring of toxic and related pollutants found in ambient and source atmospheres. Covering a wide range of measurement topics and superbly supported by 57 exhibitors of instrumentation and consulting services, the symposium was enthusiastically received by more than 700 attendees from the United States and other countries. This overview contains a selection of the highlights from the technical presentations. A synopsis of the keynote address to the symposium is also included. PMID- 2575141 TI - Effects of the mechanical energy of multi-tableting compression on the polymorphic transformations of chlorpropamide. AB - The effects of the mechanical energy of tableting compression on the polymorphic transformation of chlorpropamide have been examined. A single-punch eccentric tableting machine with a load cell and a non-contact displacement transducer were used to measure compression stress, distance and energy. An amount of 100 mg of the stable form A or the meta-stable form C of the drug was loaded into the press and the sample compressed with a compression stress of 196 MPa at room temperature (20 degrees C). The compression cycle was repeated from 1 to 30 times. The powder X-ray diffraction profiles of the deagglomerated compressed sample powder were measured to calculate the polymorphic content. The results on forms A and C suggested that both forms were transformed into each other in the solid state by mechanical energy during tableting. The contents of forms A and C reached equilibrium at a constant value above 100 J g-1 of compression energy after more than 10 cycles. After 30 tableting cycles of forms A and C, the contents of A, C and the non-crystalline solid were almost constant at about 45, 25 and 30%, respectively. The compression energies were estimated to be about 500 600 J g-1. From the results it seems that the transformation mechanism of forms A and C during tableting were as follows. The crystal form of A or C was converted to a non-crystalline solid by the mechanical energy, and the solid was then transformed into form A or C. PMID- 2575142 TI - Characterization of albumin-alginic acid complex coacervation. AB - Complex coacervation of albumin and alginic acid has been investigated to characterize this process, and to prepare a microencapsulation system suitable for the encapsulation of live cells, protein and polypeptide drugs. The optimum conditions of pH, ionic strength and total polyion concentration were in accordance with predictions based on the method of Burgess & Carless (1984). Albumin/alginic acid complex coacervation appears to fit the Vies-Aranyi model for complex coacervation. Coacervation was limited compared with other polypeptide/polysaccharide systems such as gelatin and acacia, with albumin/alginic acid complex precipitates rather than complex coacervates forming under certain conditions. In particular coacervation was limited to concentrations below 0.5% w/v. At concentrations between 0.35 and 0.5% w/v both complex coacervation and precipitation occurred, and at concentrations above 0.5% w/v only precipitation was detected. The albumin/alginic acid complex coacervate is very viscous and this together with the limited conditions governing the occurrence of coacervation makes this system unsuitable for the preparation of microcapsules. PMID- 2575143 TI - Thermodynamics of the binding of phenothiazines to human plasma, human serum albumin and alpha 1-acid glycoprotein: a calorimetric study. AB - A flow microcalorimetric study has been carried out to investigate the interactions between phenothiazine derivatives and human plasma, human serum albumin (HSA) and alpha 1-acid glycoprotein (AGP) at pH 7.4 and 37 degrees C. The direct analyses of enthalpic titration curves allowed the determination of the binding enthalpy change (delta H), the apparent binding constant (K), and the number of the binding sites (n), as well as the evaluation of the apparent free energy (delta G), and entropy (delta S) changes. The overall binding of phenothiazines was exothermic with negative delta H, which was compensated for by changes in delta S. The values of delta G were relatively insensitive to variation in the molecular details of the binding reaction. HSA possessed two classes of binding sites for phenothiazines. The first (n1 = 1), with high affinity (K1 = 10(5)-10(6) M-1) was characterized by small negative delta H and positive delta S values due to hydrophobic interaction. The second class of sites had a low affinity (K2 = 10(3)-10(4) M-1) and high capacity (n2 = 3-8) and contributed to the negative delta H and delta S values. The binding and thermodynamic parameters were influenced by the aliphatic side chain moieties on the phenothiazine nucleus. On the other hand, the drugs were bound to AGP at a single common binding site with a binding affinity of the order of 10(4)M-1, characterized by negative delta H and delta S values, which partially reflected the effect of a van der Waals' interaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575144 TI - The pharmacokinetics and pharmacodynamics of a new thromboxane synthetase inhibitor, 6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid (DP-1904), in man after single oral administration. AB - The pharmacokinetics of DP-1904, a new potent and selective thromboxane synthetase inhibitor and its effects on ex-vivo prostanoid formation were studied in Japanese normal male volunteers, who received orally a single 10, 20, 50, 100, 200, 400 or 800 mg dose. The drug was well tolerated by all subjects without evidence of any adverse reactions. The absorption of DP-1904 from gastro intestinal tract was rapid. After oral doses of 10-800 mg of the drug given to volunteers in the fasted state, the mean maximum drug concentrations in plasma (Cmax) (mean +/- s.e., n = 5) of 0.215 (+/- 0.041), 0.399 (+/- 0.037), 1.47 (+/- 0.22), 2.86 (+/- 0.22), 4.66 (+/- 0.58), 7.28 (+/- 0.72) and 16.9 (+/- 2.6) micrograms mL-1 were reached within 1 h. DP-1904 concentrations declined monophasically after Cmax with half lives of 30-40 min. These half lives were independent of the administered doses. The mean area under the concentration-time curves (AUCs) increased from 0.398 (+/- 0.038) to 30.0 (+/- 2.7) micrograms h mL 1 as the dose increased from 10 to 800 mg. Linear relations between the doses and Cmax and AUCs were observed. The correlation coefficients for Cmax and AUC were 0.930 and 0.960, respectively. The apparent oral clearance (CL/F) and renal clearance (CLR) did not change significantly as dose increased from 10 to 800 mg. The kinetics of DP-1904 proved to be linear in the dose range studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575145 TI - Dual effects of zinc sulphate on ethanol-induced gastric injury in rats: possibly mediated by an action on mucosal blood flow. AB - The present study examines the protective effect of zinc sulphate against ethanol induced gastric mucosal ulcers in rats. Absolute ethanol decreased the gastric mucosal blood flow and produced haemorrhagic lesions in the glandular mucosa. Zinc sulphate preincubation in an ex-vivo stomach chamber preparation prevented the formation of ethanol-induced lesions and attenuated the decrease of blood flow produced by ethanol. Subcutaneous injection of the same doses of the drug at 15 and 30 min before ethanol exposure, markedly reduced the blood flow and also aggravated ethanol-induced gastric injury; however, when injected at 23 and 24 h before ethanol administration, zinc sulphate protected against lesion formation but had no effect on the vascular changes induced by ethanol in the gastric glandular mucosa. These findings show that the antiulcer effect of zinc sulphate occurs only when the drug is given orally, or injected s.c. 23 and 24 h before ethanol challenge. Furthermore, this protective action is probably not entirely mediated by preservation of the gastric mucosal blood flow. PMID- 2575146 TI - Locomotor behaviour of selective dopamine agonists in mice: is endogenous dopamine the only catecholamine involved? AB - The purpose of the study was to determine the effect alone and in combination of the selective dopamine (DA) agonists SKF 38393 (D1-) and B-HT 920 (D2-) on the locomotor activity of reserpine pretreated mice (5 mg kg-1 i.p.). After 4 h, reserpine-B-HT 920 (up to 20 mg kg-1 s.c.) did not induce locomotor activity whereas SKF 38393 was markedly effective at high doses (greater than or equal to 30 mg kg-1 s.c.). In contrast, at 24 h, reserpine-B-HT 920 (0.2-6 mg kg-1 s.c.) elicited considerable locomotor activity and SKF 38393 (1-100 mg kg-1 s.c.) was effective at lower doses when compared with the corresponding 4 h reserpine experiments. When, however, these animals additionally received alpha-methyl-p tyrosine (alpha MPT; 300 mg kg-1 i.p., at 4 h before the DA agonists) neither B HT 920 (0.2-20 mg kg-1 s.c.) nor SKF 38393 (1-100 mg kg-1 s.c.) had an effect of their own. When B-HT 920 was tested in the presence of a fixed-dose of SKF 38393 (10 or 3 mg kg-1 s.c., combination experiments) B-HT 920 (0.6-20 mg kg-1 s.c.) induced considerable locomotor activity at 4 h post reserpine. At 24 h post reserpine the dose-response curve of B-HT 920 (0.06-20 20 mg kg-1 s.c.) was shifted to the left and the maximum effect was greatly increased. When additional alpha MPT was given, the dose response curve was the same but the maximum effect was markedly reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575147 TI - Use of strips containing tetracycline hydrochloride or metronidazole for the treatment of advanced periodontal disease. AB - Strips containing tetracycline hydrochloride or metronidazole 25% in polyhydroxybutyric acid as a biodegradable polymer matrix, showed sustained release in simulated gingival fluid pH 6.6 at 37 degrees C. When evaluated in patients suffering from advanced periodontal disease, the greatest response to therapy was observed with tetracycline hydrochloride strips inserted into periodontal pockets at four-day intervals for 16 days, compared with an untreated control group. A reduction in plaque index, gingival index and pocket depth was observed. A favourable alteration occurred in the microbial flora of treated pockets with an increase in the proportion of cocci and decrease in gram-negative rods, fusiforms and spirochetes. Metronidazole strips or root-planning tended not to be as effective. The clinical improvement produced by each treatment was not maintained when treatment was terminated. PMID- 2575148 TI - Influence of plasma protein binding on the brain uptake of an antifungal agent, terbinafine, in rats. AB - The intracarotid injection technique has been used to determine the unidirectional brain uptake of an antifungal, lipophilic agent, terbinafine (Lamisil, Sandoz Basle), in the rat. Ultrafiltration showed it to be highly bound to human plasma, human serum albumin (HSA), alpha 1-acid glycoprotein (AAG) and lipoproteins (VLDL, LDL, HDL). The effect of plasma protein binding of the drug on brain uptake was also examined with the technique. The lowest brain uptake was observed in the presence of plasma (6%); it varied from 23 to 30% with physiological concentrations of VLDL, LDL and HSA and was significantly higher (43-45%) in the presence of physiological concentrations of AAG and HDL. The free fraction as determined in-vitro and the brain uptake of the drug varied inversely with the plasma protein concentrations; however, the brain uptake was higher than expected from in-vitro measurements. These data indicate that the amount of circulating Lamisil available for brain penetration exceeds its free fraction; they also show that plasma proteins differently reduce the brain transport of the drug. PMID- 2575149 TI - The inhibitory effects of cannabinoids, the active constituents of Cannabis sativa L. on human and rabbit platelet aggregation. AB - Olivetol, cannabigerol (CBG), cannabidiol (CBD), cannabinol (CBN) and tetrahydrocannabinol (delta 1-THC) were assessed for their ability to inhibit agonist-induced platelet aggregation and [14C]5-HT release. With the exception of olivetol, (40% maximal effectiveness), none of the compounds inhibited tetradecanoylphorbolacetate (TPA)-induced aggregation of human or rabbit platelets. All of these cannabinoids partially inhibited primary aggregation and totally inhibited secondary aggregation of human platelets when adrenaline was used as the agonist. Inhibition was dose-dependent over the range 10(-3)-10(-5) M. Both rabbit and human platelet aggregation induced by adenosine diphosphate was inhibited in a dose-dependent manner and the order of potency was CBG greater than CBD greater than olivetol greater than THC greater than CBN, the IC50 of CBG being 2.7 x 10(-4) M. PAF-induced aggregation of rabbit platelets was also inhibited by these compounds in a dose-dependent manner over the concentration range 10(-3) to 10(-4) M, however [14C]5-HT release was only partially prevented by the cannabinoids in a manner which did not correlate with inhibition of aggregation. PMID- 2575150 TI - A note on the use of salicylate saliva concentration in clinical pharmacokinetic studies. AB - A sequential approach is presented to the problem of determining the minimum number of blood samples needed to calculate the plasma to saliva concentration ratio to a required precision. The method was applied to salicylate concentrations obtained from six rheumatoid arthritis patients. In order to achieve a 10 per cent coefficient of variation in the plasma to saliva salicylic acid concentration ratio, on average 9 samples were required for total plasma concentration and 8 samples for unbound concentration. In some cases it was not possible to achieve the required precision with the given number of samples. Correlation of salicylic acid concentrations in saliva with total and unbound plasma concentration were equally as good. The limitations of saliva data in clinical pharmacokinetic studies are discussed. PMID- 2575151 TI - The influence of changes in buccal potential difference on the buccal absorption of propranolol. AB - A buccal potential difference (b.p.d.) exists across the mucous membrane of the mouth, which can be made less negative by contact with aspirin. The influence of changing the b.p.d. with aspirin on the buccal absorption of propranolol from a series of buffers of pH5-10 has been studied in eight volunteers. The study confirmed that the buccal absorption of propranolol was markedly pH dependent, but pretreatment of the buccal membrane with aspirin had no influence on the absorption of propranolol. PMID- 2575152 TI - Alpha 1-adrenoceptors: the ability of various agonists and antagonists to discriminate between two distinct [3H]prazosin binding sites. AB - Recently, it has been demonstrated that two distinct alpha 1-adrenoceptor binding sites showing high and low affinity for WB-4101 (2-(2,6-dimethoxyphenoxy)ethyl aminomethyl-1,4-benzodioxane) and 5-methyl-urapidil can be distinguished. In the present study we examined the ability of several agonists and antagonists to discriminate between these alpha 1-adrenoceptor binding sites. [3H]Prazosin binding to membranes of rat liver, heart, cerebral cortex and hippocampus was inhibited monophasically by butanserine, I-BE 2254 (2-(3-(4-hydroxy-3 iodophenyl)ethylaminomethyl)tetralone-hydrochloride), prazosin, rauwolscine and verapamil. In contrast, competition curves of adrenaline, oxymetazoline, amidephrine and YM-12617 (5-[2-[[2-(o-ethoxy-phenoxy)ethyl]-amino]propyl]-2- methoxybenzenesulfonamide HCl) were best described by a model of two binding sites. Chloroethylclonidine (CEC), a compound shown to irreversibly eliminate binding sites with low affinity for WB-4101, increased the proportion of high affinity binding sites for oxymetazoline and amidephrine, whereas the binding data for prazosin and adrenaline remained unchanged. These results indicate that amidephrine, oxymetazoline and YM-12617, but not the other drugs tested discriminate between different alpha 1-adrenoceptor recognition sites labelled by [3H]prazosin. PMID- 2575153 TI - Absence of pharmacokinetic interaction between ofloxacin and fenbufen in rats. AB - The possible pharmacokinetic interaction between a new quinolone and fenbufen was investigated by comparing the plasma concentration-time profiles and serum protein binding of ofloxacin, fenbufen and its active metabolite, felbinac, in rats. The rats were administered intravenous doses of ofloxacin (5 mg kg-1), fenbufen (10 mg kg-1) alone or concomitantly. The plasma elimination half-lives were about 55 min in both groups. A slight elevation of plasma concentration of ofloxacin and a small decrease of its total body clearance were observed after its coadministration with fenbufen. The extent of ofloxacin binding to rat serum tended to be slightly reduced by fenbufen which coexisted at relatively high concentrations. Plasma concentration-time curves, pharmacokinetic parameters and serum protein binding of fenbufen and felbinac were not affected by the coadministration with ofloxacin. These results suggest that any substantive pharmacokinetic interaction may be unlikely after the concomitant administration of ofloxacin and fenbufen. PMID- 2575155 TI - Amino acids dilate resistance blood vessels of the perfused rat mesentery. AB - The vasodilator effect of several L-amino acids in the perfused, noradrenaline preconstricted rat mesentery preparation has been investigated. N-alpha-Benzoyl-L arginine ethyl ester (BAEE) (ED50, 1.4 +/- 0.09 mumol) and L-alanine methylester (ED50, 0.9 +/- 0.007 mumol) were the most potent although L-arginine methylester, hydroxamate and hydrochloride, N-alpha-benzoyl-L-arginine methyl ester (BAME), L methionine methylester, L-lysine hydroxamate and L-glutamic acid methylester exhibited similar potency with ED50 values in the range 2.4-3.7 mumol. L Homoarginine chloride was inactive at doses up to 20 mumols. D-Arginine hydrochloride and D-lysine hydroxamate were inactive at doses up to 50 mumols whilst D-methionine methylester (50 mumols) produced small falls in perfusion pressure in only 3 out of 7 preparations studied. Responses to BAEE, BAME, L arginine hydrochloride, L-alanine methylester, L-methionine methylester, L-lysine hydroxamate and acetylcholine (but not nitroprusside) were significantly inhibited by CHAPS (4.7 mg mL-1, 30 s) de-endothelialization as well as pretreatment of mesentery preparations with gossypol (3 microM). Responses to BAEE, BAME, L-arginine hydrochloride, L-alanine methylester and acetylcholine were similarly selectively reduced by NDGA (10 microM) pretreatment. We propose that these L-amino acids exhibit vasodilator activity in the perfused rat mesentery by virtue of releasing endothelium-derived nitric oxide (EDNO). PMID- 2575154 TI - Assessment of topical non-steroidal anti-inflammatory drugs. AB - A new non-invasive technique for assessing the efficacy of topical non-steroidal anti-inflammatory drugs (NSAID) in man is proposed. The NSAID are initially applied to the skin under occlusion before inflammation is induced by a methyl nicotinate solution. The inflammatory response is quantified in terms of cutaneous blood flow by a laser Doppler velocimeter (LDV). The efficacy of NSAID preparations is calculated by comparing the responses of the LDV to the methyl nicotinate challenge on the pretreated and the non-treated skin sites. This protocol has been used to investigate the effect of three different NSAID preparations (indomethacin, niflumic acid, palmitoyl collagenic acid) and the influence of the vehicle on the efficacy of indomethacin. The three preparations tested gave positive results but with different amplitudes in response. The efficacy of indomethacin varied with the vehicle used. PMID- 2575156 TI - An improved formulation of chloroquine for intramuscular administration: absorption kinetics in rabbits. AB - Intramuscular chloroquine is rapidly absorbed, even in severe falciparum malaria, and may cause potentially lethal hypotension. Less rapidly absorbed formulations should be safer. A chloroquine phosphate solution containing 2% methylcellulose 1500 released chloroquine 2.6 times more slowly than a commercial aqueous solution in an in-vitro absorption simulator. There was a log linear relationship between viscosity and release rate. The absorption pharmacokinetics of the more viscous chloroquine phosphate solution were then compared with those of a commercial solution after intramuscular injection to eight rabbits in an open cross over comparison. The rate of absorption was over three times slower with the viscous solution; median time to peak whole blood concentration with the commercial aqueous solution was 10 (range 5-20) min compared with 30 (range 10 60) min for the more viscous formulation (P less than 0.05). Peak whole blood concentrations were 66% (95% CI 50-82%) of those with the commercial preparation, but the acute bioavailability of the two solutions was similar. This simple new formulation may be safer than currently available chloroquine preparations and should now be evaluated in man. PMID- 2575157 TI - The influence of monoamine oxidase activity on the release of noradrenaline by tyramine. AB - The influence of monoamine oxidase (MAO) activity on the kinetic characteristics of noradrenaline (NA) release evoked by tyramine has been examined. Dog splenic artery strips were incubated with [3H]NA after inhibition of catechol-O-methyl transferase (COMT) and of extraneuronal uptake. In some experiments MAO was also inhibited. The strips were then perifused for 200 min. Some strips were exposed to tyramine (1.5, 40 and 3240 mumols L-1) from the 100th to the 200th min of perifusion. In control experiments (i.e. in the absence of tyramine) most of the [3H]NA accumulated in the strips (83% of tissue activity) and did not contribute to the efflux. The value of this "bound fraction" (the NA located at a site(s) from which it could not be displaced by a simple concentration gradient) was the same whether or not MAO was inhibited. At all concentrations, tyramine mobilized only one NA compartment. Increasing the concentration of tyramine resulted in a decrease of the "bound fraction", which became negligible for the highest concentration of tyramine used (3240 mumols L-1), regardless of MAO being inhibited or not. However, for the lower concentrations of tyramine, MAO inhibition resulted in an increase in the amine's releasing effect. The formation of 3,4-dihydroxy-phenylglycol (DOPEG) increased with increase of tyramine from the 1.5 to 40 mumols L-1 concentration, but not beyond. The ratio NA/DOPEG increased for all concentrations of tyramine. Thus, it was not possible to exclude an inhibitory effect of tyramine on MAO activity with the highest concentration used. PMID- 2575158 TI - Studies on the effects of omeprazole on thyroid function in the rat. AB - The effects of omeprazole (an H+, K+ -ATPase inhibitor) on thyroid parameters in rats have been examined. SK&F Wistar rats were dosed orally with omeprazole (up to 500 mg kg-1) or vehicle. Treatment for 7 or 14 days resulted in generally decreased plasma T3 concentrations in males (with little change or slight increases in females) and increased serum TSH concentrations (22%-68% increases). No changes were detected in thyroid 125I uptake or organification. Liver 5' deiodinase activity was decreased in male rats after 7 days treatment. Thyroxine clearance was not altered after a single dose of omeprazole. In-vitro studies showed omeprazole to be only a weak inhibitor of TSH-stimulated 125I organification in cultured porcine thyrocytes. It is concluded that omeprazole has weak effects on the pituitary-thyroid-liver axis, its main action being to inhibit the peripheral deiodination of thyroid hormones. PMID- 2575159 TI - The relevance of the presence of certain synthetic steroids in the aquatic environment. AB - Norethisterone and ethinyloestradiol concentrations in sewage effluent, reservoirs, rivers and potable water have been estimated at less than 20 ng L-1, a value unlikely to present a significant risk to human health. PMID- 2575160 TI - Long-term potentiation and N-methyl-D-aspartate receptors in the visual cortex of young rats. AB - 1. Long-term potentiation (LTP) of synaptic transmission following tetanic stimulation of the white matter was studied by recording extracellular field potentials and intracellular synaptic potentials from layer II/III of visual cortical slices from young rats ranging in age from 21 to 40 days. 2. Single shocks applied to the white matter at 0.1 Hz, used as test stimuli, elicited field potentials that consisted of primary and secondary components. The removal of Ca2+ ions from the perfusate allowed identification of the secondary component as originating postsynaptically and the primary one as reflecting a mixture of antidromic and postsynaptic potentials. 3. Tetanic stimulation at 5 Hz for 60 s was delivered to the white matter and field potentials were observed for 20 min to 9 h after the tetanus. LTP was defined as being present when the response displayed more than a 20% increase in amplitude of the Ca2+-sensitive components 20 min after the tetanus. LTP was induced in twelve of twenty-three slices tested, and this potentiation lasted throughout the period of observation. The average magnitude of potentiation was 147.8 +/- 28.4% of the control value for the twelve slices. 4. Administration of D,L-2-amino-5-phosphonovalerate (APV), an antagonist selective for N-methyl-D-aspartate (NMDA)-preferring receptors, slightly reduced the amplitudes of Ca2+-sensitive components of the field potentials. The average magnitude of reduction was 80.2 +/- 15.3% of the pre-drug control values. In the presence of APV, LTP was induced in only one slice of twelve tested. 5. Stable intracellular recordings were obtained from twenty-three cells from layer II/III. Excitatory postsynaptic potentials (EPSPs) evoked by white matter stimulation had mean onset and peak latencies of 4.1 and 11.3 ms, respectively. In some cells these fast EPSPs were followed by another slow EPSP with a much longer latency and higher amplitude. Administration of APV revealed further that the fast EPSPs consisted of two components, i.e. early and late components. 6. Tetanization of the white matter induced long-lasting enhancement of EPSPs in eight of twelve cells tested. In five of these eight cells, fast EPSPs were enhanced in amplitude and in the remaining three cells, slow EPSPs appeared de novo after the tetanus. 7. APV reduced the amplitudes of the fast EPSPs and abolished the slow EPSPs if present. The average magnitude of reduction for the fast EPSPs was 65.6 +/- 15.1% and this reduction was due mainly to an elimination of the late component.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2575161 TI - Identification of ionic currents at presynaptic nerve endings of the lizard. AB - 1. Ionic currents associated with the invasion of an action potential into the motor nerve ending of the lizard, Anolis carolinensis, were measured with a focal extracellular electrode at several locations along the nerve ending. 2. These experimentally observed currents could be matched with computer simulations of action potential propagation into the nerve ending. They revealed that while Na+ channels are the major ionic current pathway in the heminode, K+ channels provide the major pathway in the terminal branches and boutons. 3. Calcium current in the presynaptic ending was unmasked by the application of tetraethylammonium (TEA). This current was blocked by: (a) cadmium, (b) omega-conotoxin GVIA and (c) nifedipine, but was unaffected by nickel at concentrations less than or equal to 100 microM. Nifedipine's action became more definitive when the duration of the action potential was greatly extended by pre-treatment with TEA. The effect of Bay K 8644 was inconsistent. 4. Transmitter release, as measured by postsynaptic current, had a pharmacological response profile similar to that of the Ca2+ current, with the exception that transmitter release was increased reliably and reversibly by Bay K 8644. 5. This pharmacological response profile is identical to that of the L type Ca2+ channel identified by Fox, Nowycky & Tsien (1987 alpha) in chick dorsal root ganglion neurones. We saw no evidence for more than a single type of Ca2+ channel in lizard motor nerve endings. 6. A calcium-activated K+ current IK(Ca) was revealed by application of 3,4-diaminopyridine (DAP), a delayed-rectifier K+ channel blocker. This K(Ca) current was blocked by TEA, charybdotoxin and by substitution of cobalt for extracellular calcium. PMID- 2575162 TI - Effects of new non-N-methyl-D-aspartate antagonists on synaptic transmission in the in vitro rat hippocampus. AB - 1. The effects of new, potent non-N-methyl-D-aspartate (NMDA) receptor antagonists, 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7 nitroquinoxaline-2,3-dione (CNQX), have been examined using intra- and extracellular recordings in the hippocampal slice preparation. In terms of potency and selectivity, the action of the two blockers was similar and CNQX was used in most experiments. 2. CNQX reduced the responses to ionophoretic applications of the non-NMDA agonists kainate (KAI) and quisqualate (QUIS) with IC50 values of 1.2 and 4.8 microM, respectively. In Mg2+-free solutions responses to NMDA were generally not affected by concentrations of CNQX up to 25 microM. 3. The action of CNQX was only slowly and poorly reversible on washing. Responses to QUIS and KAI were also reversibly reduced by ionophoretic application of CNQX. 4. CNQX blocked the evoked EPSP in CA1 and CA3 neurones with an IC50 of around 2 microM, which is similar to the IC50 for responses to KAI. CNQX was without effect on the passive membrane properties, the afferent volley and paired pulse potentiation. 5. In the presence of CNQX (greater than 5 microM) a small EPSP remained which was largest in CA1 neurones. It was blocked by low concentrations of the NMDA receptor antagonist (+/-)-2-amino-5-phosphonovaleric acid (APV), was markedly enhanced on removing Mg2+ ions from the bathing medium and, in voltage clamp experiments, showed a potential dependence which is characteristic of the NMDA ionophore. 6. The latency of the APV-sensitive EPSP in CA1 was the same as the CNQX-sensitive EPSP, indicating that NMDA receptors participate in monosynaptic excitation. 7. Feedback and feed-forward inhibition in both area CA1 and CA3 were sensitive to CNQX. There seemed to be two components of the inhibition, both of which appear to be GABAergic since they could be blocked by picrotoxin (PTX), but only one of which was blocked by CNQX. The CNQX-resistant IPSP was not affected by APV. 8. In conclusion, quinoxalinediones have been used to demonstrate that non-NMDA receptors mediate the majority of the EPSP. Additionally, a component of the EPSP in CA1 is mediated by NMDA receptors and is manifested at resting membrane potentials and in the presence of Mg2+. PMID- 2575163 TI - Adrenoceptor profile of blood vessels in the knee joint of the rabbit. AB - 1. An in vitro preparation of the rabbit knee joint, perfused with oxygenated Locke solution, was used to assess the nature of adrenoceptors within articular blood vessels. 2. Dose/response relationships were obtained to intra-arterial injection of alpha- and beta-adrenoceptor agonists. 3. Adrenaline and noradrenaline produced a similar pattern of increasing constriction of articular vessels with increasing dose of drug. 4. The alpha 1-agonist, phenylephrine, also produced dose-dependent constrictor responses, but the alpha 2-agonist; clonidine, had no effect. The alpha 2-agonist UK-14304 did, however, produce modest vasoconstriction which was not greatly altered by the alpha 1-blocker prazosin. The constrictor effect of noradrenaline was abolished by both the alpha 1,2-blocker phenoxybenzamine and by prazosin but not by the alpha 2-blocker rauwalscine. 5. The beta-adrenoceptor agonist, isoprenaline, had little effect at a dose of 10(-6) M or lower, but gave rise to a constrictor effect at higher concentrations. This response was blocked by phenoxybenzamine but not by the beta 1,2-blocker propranolol, suggesting that the constrictor effect was mediated via alpha-adrenoceptors. 6. The results suggest that alpha 1- and alpha 2 adrenoceptors are present within articular blood vessels, but that beta-receptors are absent. The effects of noradrenaline appear to be mediated principally via alpha 1-adrenoceptors. PMID- 2575164 TI - Intracellular calcium mobilization triggered by a glutamate receptor in rat cultured hippocampal cells. AB - 1. Intracellular free calcium ([Ca2+]i) was monitored by means of Fura-2 fluorescence measurements in hippocampal cells in primary cultures from newborn rats. 2. In external media containing 200 microM-DL-2-amino-5-phosphonovalerate and 1 mM-kynurenate, but no added Ca2+, an increase in [Ca2+]i was observed in 30 40% of cells examined in response to quisqualate or L-glutamate. 3. Under such conditions, [Ca2+]i often increased gradually with a latency of a few seconds after application of the agonists. 4. Pre-treatment of the cultured cells with pertussis toxin reduced the extent of quisqualate-stimulated [Ca2+]i increase in Ca2+-free media, but the percentage of the responsive cells was not affected appreciably. 5. It is concluded that quisqualate and L-glutamate can trigger the release of Ca2+ from intracellular Ca2+ stores, most likely by activating a glutamate receptor coupled to a pertussis toxin-sensitive G-protein. PMID- 2575167 TI - High levels of oral yeasts in early HIV-1 infection. AB - Ten human immunodeficiency virus-1 (HIV-1) infected homosexual or bisexual individuals (ages 24-45) with no history of opportunistic infection were examined, by culture, for the presence of yeasts in whole saliva and on oral mucosa. All were HIV-1 antibody-positive men, non-smokers, non-denture wearers, and taking no medication. The mean salivary level of yeast was four logs higher in the HIV-1 infected group compared to a control group of normal, unmedicated, non-smoking men (ages 20-41) who denied any risk behavior for HIV-1 infection. Identification of the yeast in these HIV-1 positive individuals established that Candida albicans was the predominant species found in whole saliva and on buccal mucosa and tongue. Distinct hyphae were observed with only one mucosal sample. No significant correlation was found between whole saliva yeast concentration and the T4/T8 lymphocyte ratios or absolute number of T4 cells. No correlation was observed between oral yeast concentration and anti-C. albicans IgA titers. The high level of oral yeast in these individuals prior to the development of opportunistic infections is consistent with the suggestion that oral defense mechanisms are compromised in individuals following HIV-1 infection. PMID- 2575165 TI - Giant synaptic potentials in immature rat CA3 hippocampal neurones. AB - 1. Intracellular recordings were made from rat CA3 hippocampal neurones in vitro during the first eighteen days of postnatal life. The cells had resting membrane potentials more negative than -51 mV, action potentials greater than 55 mV and membrane input resistances of 117 +/- 12 M omega. An unusual characteristic of these cells was the presence of spontaneous giant depolarizing potentials (GDPs) which were observed during the first eight postnatal (P) days in over 85% of neurones. They were less frequent between P9 and P12 (48%) and disappeared after P12. 2. The GDPs were synchronously generated by a population of neurones; they reversed polarity at -27 mV when recorded with KCl-containing electrodes and at 51 mV with potassium acetate- or potassium methylsulphate-filled electrodes. 3. The GDPs were blocked by bath application of bicuculline (10 microM) or picrotoxin (100-200 microM). Exogenously applied gamma-aminobutyric acid (GABA; 0.2-1 mM) induced at resting membrane potential a bicuculline-sensitive membrane depolarization which reversed polarity at -25 and -51 mV when recorded with KCl- or potassium methylsulphate-filled electrodes respectively. 4. The GDPs were reduced in frequency or blocked by the N-methyl-D-aspartate (NMDA) receptor antagonists DL-2-amino-7-phosphonoheptanoate (AP-7; 50 microM), D(-)2-amino-5 phosphonovalerate (AP-5, 10-50 microM) and (+-)3-(2-carboxypiperazin-4-yl)-propyl 1-phosphonic acid (CPP, 10-50 microM) or NMDA channel blockers phencyclidine (2 microM) and ketamine (20 microM). 5. Stimulation of the hilus during the first week of life evoked a GDP followed by a hyperpolarization. The GDPs were generated by a population of synchronized neurones and reversed polarity at -27 mV with KCl-filled electrodes and at -52 mV with potassium acetate- or potassium methylsulphate-containing electrodes. 6. Bath application of bicuculline (1-10 microM) or picrotoxin (100-200 microM) reversibly blocked the evoked GDPs in the majority of cells. The NMDA receptor antagonists AP-5 (50 microM), AP-7 (50 microM) and CPP (30 microM) usually reduced the amplitude and the duration of the evoked GDPs. In neurones in which evoked GDPs were blocked by bicuculline, a NMDA mediated component was revealed by increasing the strength or the frequency of stimulation. 7. During the second week of postnatal life, when spontaneous GDPs were extremely rare or absent, superfusion with bicuculline (10 microM) induced, as in adult slices, interictal discharges. These reversed polarity near 0 mV with KCl- or potassium acetate-containing electrodes and were reduced in amplitude and duration by AP-5 (50 microM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2575166 TI - Baroreceptor-vasomotor reflex after N-methyl-D-aspartate receptor blockade in rabbit caudal ventrolateral medulla. AB - 1. Experiments were performed in anaesthetized rabbits to determine whether blockade of N-methyl-D-aspartate receptors in the caudal ventrolateral medulla oblongata prevents the changes in renal sympathetic vasomotor activity which normally occur in response to increases or decreases in arterial pressure. 2. N Methyl-D-aspartic acid receptor blockade using bilateral injections of either kynurenic acid (5 nmol) or DL-amino-5-phosphonovaleric acid (5 nmol) caused a rise in arterial pressure with a variable change in renal sympathetic nerve activity. 3. The depressor and renal sympathoinhibitory responses normally seen after intramedullary injection of N-methyl-D-aspartic acid (50 pmol) into the caudal ventrolateral medulla were entirely prevented by prior receptor blockade. The corresponding responses to L-glutamate (10 nmol) were not affected. 4. The depressor and renal sympathoinhibitory responses normally seen with electrical stimulation of the aortic depressor nerve were abolished by the receptor blockade. 5. The reflex inhibition of renal sympathetic nerve activity normally seen in response to increasing arterial pressure using a cuff around the descending aorta was not affected by kynurenic acid. The response was reduced by DL-amino-5-phosphonovaleric acid but a significant degree of inhibition was preserved. The reflex increase in renal sympathetic nerve activity normally seen in response to reducing arterial pressure using a cuff occluder around the inferior vena cava was unchanged after injection of DL-amino-5-phosphonovaleric acid and was increased in magnitude after injection of kynurenic acid. 6. The results indicate that blockade of excitatory amino acid receptors in the caudal ventrolateral medulla of the rabbit abolishes the depressor response evoked by electrical stimulation of the aortic nerve but leaves intact the normal baroreceptor-vasomotor responses elicited by raising or lowering arterial pressure. PMID- 2575168 TI - Corrosion properties of soldered joints. Part I: Electrochemical action of dental solder and dental nickel-chromium alloy. AB - The corrosion properties of contact between six Ni-Cr alloys and two dental solders were evaluated. Ni-Cr alloys with low Cr content coupled with silver solder induced continuous galvanic current, whereas Ni-Cr alloys with high Cr and some Mo content coupled with silver or gold solder induced galvanic current for a short time. Six Ni-Cr alloys were divided into two groups according to the dissolution of Ni, one with low resistance and the other with high resistance. The initial equilibrium was induced between high resistance Ni-Cr alloys and both solders by less current density, which implies a smaller degree of corrosive current than that in low-resistance alloys. Corrosion was observed in the silver solder coupled with high-resistance Ni-Cr alloy, but was not found in the gold solder coupled with both alloys. In soldering Ni-Cr alloy, it is better to use a gold solder and a high-resistance Ni-Cr alloy for corrosion resistance. PMID- 2575170 TI - The new H2-antagonists--are we prescribing them? PMID- 2575171 TI - Asthma--still a challenge for general practice. PMID- 2575172 TI - The sleep-wake-cycle: basic mechanisms. AB - The physiologic characteristics of the sleep-wake states have been well defined and some of the chemical and neuron systems that participate in the cyclic generation and maintenance of these states have been identified. The actual dynamic process by which these systems interact to generate the basic sleep-wake cycle, however, remains a mystery. PMID- 2575173 TI - Relationship between serum gamma-glutamyl transpeptidase activity, blood pressure and alcohol consumption. AB - The associations among alcohol consumption, gamma-glutamyl transpeptidase (gamma GTP) activity in serum and blood pressure (BP) were analysed in a cross-sectional study of 1,156 healthy male workers 35 to 59 years of age, consisting of 349 non drinkers, 682 light-daily drinkers (consuming less than 58 ml of alcohol per day) and 125 heavy-daily drinkers consuming more. No marked elevation of BP with high alcohol consumption was seen in the present subjects. On the other hand, a linear elevation of BP together with an increase in serum gamma-GTP activity was found in subjects above 40 years of age. The BP levels corresponding to the three different drinking habits, non-drinkers, light drinkers and heavy drinkers, were similar to each other regarding gamma-GTP levels. The relationship between gamma GTP and BP was shown, by multiple regression analysis, to be independent of age, obesity and the dose of alcohol consumed. The contribution to the rise in BP of the dose of alcohol consumed, in comparison with that of gamma-GTP, was negligible. Serum gamma-GTP activity is a useful indicator of the susceptibility to the pressor effect of alcohol. PMID- 2575174 TI - Doxazosin, a new alpha-1-antagonist drug, controls hypertension without causing airways obstruction in asthma and COPD. AB - The treatment of systemic hypertension in patients with coexisting chronic airflow limitation is difficult. Even a 'cardioselective' beta-blocker potentially can increase airflow limitation. However it is very unlikely that alpha 1 blockers can bronchoconstrict. We have therefore evaluated the efficacy and safety of doxazosin, a new orally active selective alpha 1 blocker, in patients with systemic hypertension with concomitant airflow limitation. We studied 21 patients (11M, 10F) whose diastolic blood pressure was 95-114 mmHg and FEV1 22-73% of predicted. In the 19 patients who completed the study the dose of doxazosin to achieve satisfactory control of the systemic hypertension lay between 1 and 16 mg (mean 6 +/- 3.6 mg). This doxazosin dosage reduced the diastolic blood pressure on average from 103 to 91 mmHg (P = 0.0001). However this produced no significant changes in peak expiratory flow rate (PEFR) over the days of the study (P greater than 0.05). The mean variations in PEFR both 'day to day' (P less than 0.001) and 'within day' (P less than 0.002) were reduced during doxazosin therapy, and FEV1 rose on average from 1.6 to 1.7 (P less than 0.05). We conclude that doxazosin is an effective oral antihypertensive drug, which does not exacerbate pre-existing airflow limitation. PMID- 2575175 TI - Hypertension, lipids and alpha-blockade. Proceedings of an international symposium. Paris, France, 27 May, 1989. PMID- 2575176 TI - Interactions between antihypertensive agents, serum lipids and cigarette smoking in high risk hypertensive patients. AB - Treatment of hypertension aims at preventing strokes and coronary events. Although diuretics and beta-blockers lowered blood pressure effectively and allowed prevention of strokes in large-scale trials, they did not reduce the incidence of myocardial infarction or coronary death. The failure of diuretics and beta-blockers to afford cardiac protection may be due in part to the unfavourable effects of these agents on associated risk factors like hyperlipidaemia and smoking. Hyperlipidaemia is more prevalent in hypertensive patients than in matched normotensive controls, and the combination of hyperlipidaemia and smoking is more frequent than can be expected to occur by chance. Diuretics and beta-blockers affect lipid metabolism negatively. Unlike these agents, alpha-blockers do not alter serum lipids and might reduce triglyceride and cholesterol levels. Several trials have shown that the outcome of treatment with beta-blockers was less favourable in smokers than in non smokers in terms of blood pressure control and prevention of coronary events. A possible explanation is provided by acute experiments in which beta-blockade enhanced the systemic and coronary vasoconstriction elicited by smoking, while alpha-blockade had the opposite effect. Although there is reason to believe that alpha-blockers may be preferable to diuretics and beta-blockers for the treatment of high risk hypertensive patients who smoke and/or exhibit high levels of serum lipids, there is a need for larger and longer trials to test their ability to reduce cardiovascular risk. PMID- 2575177 TI - Metabolic changes during antihypertensive therapies. AB - There is controversy whether various classes of antihypertensive drugs can reduce significantly cardiovascular morbidity and mortality in primary prevention. A failure to show this in many studies was attributed, at least in part, to deleterious effects of these drugs on lipid metabolism. Especially adrenergic antihypertensives cause marked effects on lipoprotein levels in plasma. A review of the literature revealed that beta-blockers increase triglycerides and VLDL (very low density lipoprotein)-cholesterol and may lower plasma HDL (high density lipoprotein) levels. In contrast alpha 1-adrenergic inhibitors like prazosin, doxazosin and terazosin lower triglycerides, total cholesterol, LDL (low density lipoprotein)- and VLDL-cholesterol and increase plasma HDL levels. The mechanisms by which alpha- and beta-blockers may produce the observed effects on plasma lipids and lipoproteins are not well understood. It has been shown in our laboratory that the activity of the LDL receptor of peripheral cells, a major determinant of cholesterol levels in plasma, is regulated by catecholamines via alpha 2- and beta 2-adrenergic receptors. Accordingly, blockade of these adrenoceptors with alpha- and beta-adrenergic antagonists can reverse the catecholamine effect. In addition these agents may affect lipoprotein lipase, lecithin cholesteryl acyltransferase and cholesterol ester hydrolase. These data may explain, at least in part, the plasma effects. However, long-term studies are needed to clarify the clinical value of antihypertensives with different metabolic profiles. PMID- 2575178 TI - Alpha 1-blockers, their antihypertensive efficacy and effects on lipids and lipoprotein. AB - Alpha adrenergic receptor-blocking drugs lower the blood pressure but until prazosin, a post synaptic alpha 1 receptor-blocking drug was introduced, they had limited clinical application. Prazosin, terazosin and doxazosin are all effective as single therapy or in combination with other anti-hypertensive drugs. As vasodilators they combine particularly well with beta adrenergic-blocking drugs. The only serious side effect, namely first dose postural hypotension, can be avoided by starting with a small dose and avoiding concomitant salt depletion. The disappointing results of trials in mild hypertension, in terms of prevention of coronary artery disease and its complications, have been attributed in part to the fact that several of the drugs used in these studies have an adverse effect on atherogenic lipids. alpha 1 adrenergic-blocking drugs have a beneficial effect on the lipid profile. Anti-hypertensive therapy usually needs to be continued on a long term, often permanent, basis. For this reason, drugs which have a beneficial effect on atherogenic lipids are preferable as initial therapy and, where possible, single therapy in the treatment of mild hypertension. PMID- 2575179 TI - Blood pressure and lipid lowering effects of terazosin. AB - Treatment of hypertension reduces the risk of developing stroke, renal failure and left ventricular failure but not that of coronary heart disease. The reasons for the less favourable results of antihypertensive regimens on coronary heart disease are manifold and unresolved. Antihypertensive treatments which in addition to their blood pressure lowering effects also favourably influence serum lipids offer greater promise to lower coronary heart disease. The long-acting postsynaptic alpha-blocker terazosin was assessed in terms of multifactorial aspects of patients with various risk profiles. The results of clinical trials underline that terazosin changes blood lipids in a beneficial direction and therefore has the potential to lower coronary heart disease more effectively than conventional antihypertensive medications. PMID- 2575180 TI - [Structure and regulation of the expression of the somatostatin gene and processing of the precursor]. PMID- 2575181 TI - [Molecular genetics of insulin receptor and its disorder]. PMID- 2575182 TI - [Expression of P-glycoprotein (multidrug-resistance gene product) in haematological tumors]. AB - The fact that cancer cell acquires multidrug resistance to carcinostatics at cancer treatment is a very important subject clinically. The mode of multidrug resistance is complicated, but the gene associated with multidrug resistance (MDR 1) has been isolated. It has become evident that MDR 1 gene carries membrane glycoprotein (P-glycoprotein) which occurs in the cell acquired drug-resistance. Assessment has been made this time regarding the occurrence of P-glycoprotein in the tumorous cells and tissues by the use of monoclonal antibody (C 219) to P glycoprotein. Occurrence of P-glycoprotein in malignant lymphoma exhibited positivity in 9 cases out of 36 immunohistologically. 170 KD P-glycoprotein was detected in 4 cases out of 10 at Western blotting analysis of the protein isolated from the nuclear cell in the peripheral blood in the patients with leukemia. Further, P-glycoprotein positive cases were all progressive cases clinically and showed resistance to treatment. From these results, it has been clarified that occurrence of P-glycoprotein in haematological tumors is related to multidrug resistance. PMID- 2575184 TI - The cellular composition in the pancreatic islet of a cow with spontaneous diabetes mellitus. PMID- 2575183 TI - Multiple endocrine neoplasia. AB - The MEN syndromes continue to be the focus of considerable interest and research. Since successful treatment requires early diagnosis, proper screening and follow up of patients at risk is important. In the individual at risk for developing MEN IIa, annual screening should include measurement of the basal and stimulated plasma CT levels, and determination of plasma levels of calcium, PTH, and CEA. Twenty-four hour urine excretion rates of norepinephrine, epinephrine, metanephrine, dopamine, and VMA should also be obtained. It is our recommendation that this screening be continued through the third decade of life. Patients having thyroidectomy for MTC need to be tested annually for recurrent MTC and the development of adrenal medullary disease. All patients at risk for developing MEN IIb should be evaluated in a similar fashion. Recently, several groups using DNA linkage analysis have mapped the gene for MEN IIa to chromosome 10, although the exact location of the gene is yet to be determined. Preliminary linkage studies have mapped the gene for MEN I to chromosome 11. The identification of the genes for MEN I and MEN II will greatly simplify the diagnosis of the disease and perhaps also the therapy of affected patients. PMID- 2575185 TI - Mosquito collection in endemic areas of Japanese encephalitis in Hokkaido, Japan. AB - A study was conducted during 1985 and 1986 to evaluate the roles of mosquito species as possible vectors of Japanese encephalitis (JE) virus in Hokkaido. The number of Culex tritaeniorhynchus was very low among the four pig farms where outbreaks of abortion caused by JE virus were observed in swine populations. At one farm near Sapporo, only one Cx. tritaeniorhynchus was found among a total of 510 mosquitoes collected during the survey period from July to October 1985, even when JE virus activity among sentinel pigs was revealed by seroconversion. At another farm in the south, no individuals of this mosquito species were found among 987 mosquitoes collected at the time of the outbreaks of abortion. Cx. pipiens pallens, Anopheles species, Aedes vexans nipponii, and Ae. japonicus were predominant over Cx. tritaeniorhynchus. Cx. tritaeniorhynchus, almost a solve vector species of JE virus in the southern part of Japan, is probably not a vector of the virus in Hokkaido. The collected mosquitoes (2,332 from 1985 and 1,403 from 1986) were processed for virus isolation but no JE virus was isolated. More extensive field studies are necessary to provide further information on the role of mosquito species other than Cx. tritaeniorhynchus in the transmission of JE virus in the northern limits of its range including Hokkaido. PMID- 2575186 TI - [Possibilities of finger substitution]. AB - Authors deal, in connection with their clinical cases, with the replacement of the fingers of the hand. Attention is called to the fact, that a minimal requirement of the reconstruction, performed on the severe, multiply amputated hand, should be the formation of a "basic hand", and that at the planning of such operations the aim may be the reconstruction of the function of the hand only. Among the methods presented the most modern methods, requiring microvascular surgical technique, are also shown. Although the right of using these is obvious, the older, however well proved methods should not be forgotten either. The possibilities of finger replantation are described didactically; considering the extent of this theme however authors did not strive to completeness. PMID- 2575187 TI - [Current observations on the morphology and biomechanics of the human flexor tendon sheath]. AB - Authors give a short description, based on own experimental work and literary data, of the tendon sheat biomechanics of the long fingers. The importance of the integrity of the tendon sheat--subcutis--skin unit is presented. Starting from this, a new possibility of exposing the flexor tendons, a laterobasal exposure is shown. The experimental character of their work is stressed, it is however underlined that clinical importance is attached to their aspect. PMID- 2575188 TI - [Reconstruction by revascularization of a hand subtotally amputated at the middle section]. AB - Authors describe the successful revascularization operation of the subtotally amputated hand of a 21 years old man. The patient was controlled after 2 years. He was satisfied with the function of the restored hand and worked in his original job. PMID- 2575189 TI - [Late results of Eggers' operation in spastic contracture of the knee]. AB - Authors assess the late results of flexor tendon transplantation in spastic flexion contracture of the knee on the basis of the follow-up of 29 cases. It is stated that the method is suitable to eliminate the flexion contracture, however it is unable to cease the gait disturbance of the basic disease, as after the Eggers' operation patients walk characteristically with extended knees and a compensating increased lumbar lordosis. These unfavourable effects may be diminished by an individually planned, selective muscle transplantation performed after a careful preoperative clinical examination, motion analysis, perhaps also after an electromyographic examination. PMID- 2575190 TI - [Experimental study of the ossification of decalcified cortical bone]. AB - Authors examined in animal experiments the ossification of decalcinated cortical bone. A more rapid rebuilding of the demineralised bone than that of the not decalcinated one, seems to them as proven. An acceleration of the process is tried by dosing anabolic steroids and calcium. PMID- 2575191 TI - [Current views on "hangman's fracture"]. AB - The international literature calls "Hangman's fracture" (HF) the injury of the upper cervical spine with characteristic lesions of the epistropheus. The typical bone lesion in this injury is the bilateral fracture of the penduncles of the epistropheus, the dislocation of the arch, the luxation between CII and CIII and the injury of the disk, by chanche other additional fractures of the vertebrae CII and CIII too. Two forms are known: that of hyperextension distraction mechanism, leading to the classical death by hanging with very severe neurological lesion, and that with hyperextension compression mechanism, seen in modern traffic injury without neurological lesion or with relatively mild neurological symptoms. The later injury, seen more and more frequently in our days, appears with a rather broad spectrum and can be divided in three types. The stable injuries can be treated conservatively, the unstable injuries with Halo traction or with anterior operative methods, according to modern requirements. The prognosis is good. Authors describe their experiences, first in the Hungarian literature, gained from a critical review of the world literature and from a 11 years material. PMID- 2575192 TI - [A case of a hip prosthesis replaced three times in the course of 18 years]. AB - Author describes the case of a patient in whom in 1961-1979 four prostheses, thought actually to be modern, were implanted. So the development of this operation can be demonstrated in a single case. PMID- 2575193 TI - [Therapeutic possibilities in femoral neck fractures]. AB - Authors describe the therapeutic possibilities of a very rare lesion i.e. the fracture of the femoral head. After a short historical and theoretical review 3 operated cases are reported and possibilities of the treatment of complications are also discussed. PMID- 2575194 TI - [Consolidation of congenital tibial pseudoarthrosis using Ilizarov's compression distraction method]. AB - Authors describe a case of consolidation of a congenital pseudarthrosis. The difficulties of the treatment of this disease are known. Very few procedures can secure the internal fixation and the induction of osteogenesis in the same time. Authors used beside internal fixation the distraction method that led to a surprisingly quick consolidation. PMID- 2575195 TI - [Scott's operation in the management of recurrent posterior dislocation of the shoulder]. AB - Authors describes the clinical features of the rare posterior dislocation of the shoulder. The conservative and operative methods of treatment are presented. Scott's operation, used in his cases and the favourable experiences, gained with this method are described in details. PMID- 2575196 TI - [Treatment of scaphoido-trapezial arthrosis by arthrodesis using small-size Ender plates]. AB - Authors have performed in the treatment of arthrosic complaints a scaphoideo trapezial arthrodesis. The axial compression was reached with the application of small Ender plates without damaging the articular surface of the neighbouring small joints of the wrist. In the literature, describing the scaphoideo-trapezial arthrodesis, no similar operative technique was found. PMID- 2575197 TI - [Penetration of the infection caused by type 2 human immunodeficiency virus in Andalusian individuals at risk]. PMID- 2575198 TI - [Pulmonary disease induced by salazopyrine coexisting with pulmonary tuberculosis]. PMID- 2575199 TI - [Remission of benzodiazepine-resistant delirium tremens after treatment with Laborit's lytic cocktail]. PMID- 2575200 TI - [Molecular genetics. More disease genes are being found. How should this information be used?]. PMID- 2575201 TI - Hypophysectomy decreases and growth hormone increases the turnover and mass of rat liver glutamine synthetase. AB - Hypophysectomy diminishes rat liver glutamine synthetase (GS) activity and growth hormone (GH) administration restores this activity to normal levels; brain GS is unaffected. We have now investigated the effects of long-term hypophysectomy (45 day) and GH treatment on the GS mass (amount of enzyme) and turnover in rat liver and brain. Labeled GS was isolated by immunoprecipitation at intervals between one and six days after pulse administration of [U-14C] leucine and the GS half life (t1/2) was determined. The GS mass was obtained by immunoassay and by calculation using the specific activity of purified GS. GS turnover was calculated by multiplying the GS mass by the first-order rate constant of degradation (kd). During the time course of each experiment, the GS mass did not change, indicating that in each of the three hormonal states studied, a steady state existed. Hypophysectomy increased the t1/2 of hepatic GS from 3.8 to 8.8 days and decreased GS turnover from 0.38 to 0.1 microgram/100 g body wt/day; the GH regimen used restored the turnover to above normal levels, 0.6 microgram/100 g body wt/day. The GS mass decreased from 2.0 to 1.2 micrograms/100 g body wt and GH restored the GS mass to normal levels. The brain enzyme was not affected by hypophysectomy or GH. PMID- 2575202 TI - Cysteamine normalizes cerebral somatostatin level and binding in pentylenetetrazol-kindled rats. AB - Rats were kindled by intraperitoneal injection of pentylenetetrazol (PTZ) (30 mg/Kg) every 48 h. Once kindled, some of the animals received a single injection of cysteamine (200 mg/Kg). Somatostatin-like immunoreactivity (SLI) and 125 I Tyr11-somatostatin binding were measured in the frontoparietal cortex and hippocampus of the two experimental groups and the control rats. After PTZ kindling the following was observed: 1) SLI content was increased in the two areas; 2) Somatostatin receptor affinity decreased in the frontoparietal cortex and was unaltered in the hippocampus; 3) The number of somatostatin receptors decreased in the hippocampus and was unaltered in the frontoparietal cortex. Cysteamine, an agent which depletes brain somatostatin and suppresses kindled seizures in PTZ-treated rats, reversed the altered SLI levels and binding in these rats. PMID- 2575203 TI - One-dimensional chemical shift imaging of fluorinated neuroleptics in rat brain in vivo by 19F NMR rotating frame zeugmatography. AB - One-dimensional chemical shift imaging reflecting local tissue contents of the fluorinated neuroleptics fluphenazine and trifluoperazine in rat brain was obtained noninvasively in vivo using one-dimensional 19-fluorine (19F) nuclear magnetic resonance (NMR) rotating frame zeugmatography. Activities of these fluorinated neuroleptics showed a differential distribution in the brain, maximal in the deep structures presumably within the basal ganglia. An additional resonance of an unidentified fluorinated metabolite was localized to the subcutaneous tissue. The present data indicate the feasibility of chemical shift imaging of fluorinated neuroleptics using a high field NMR system and the potential for future development of neurotransmitter imaging by NMR. PMID- 2575205 TI - Paramagnetic probes of macromolecules. PMID- 2575204 TI - [Clinical indications for a new benzodiazepine: clotiazepam]. PMID- 2575206 TI - Control of coated-pit function by cytoplasmic pH. PMID- 2575207 TI - [Treatment of chronic polyarthritis]. PMID- 2575208 TI - Comparison of particulate guanylate cyclase in cells with and without atrial natriuretic peptide receptor binding activity. AB - A line of kidney cells (PK1) which does not possess measurable ANP binding but has an active particulate guanylate cyclase has been identified. The physical characteristics of this enzyme were compared with those of particulate guanylate cyclase and ANP receptors isolated from rat lung. Although receptor and enzyme appear to reside on the same protein in the lung while the cyclase from PK1 cells does not possess ANP binding activity, these proteins exhibit identical physical characteristics. Guanylate cyclase from PK1 cells and rat lung and ANP receptor from lung co-eluted during gel filtration chromatography, with a Stokes radius of 6.1 nm. Also, these activities co-migrated through sucrose density gradients with S20,w values of 10.4 to 10.9. Using these parameters, a molecular weight of about 270 kD was estimated for all three activities. Furthermore, these enzyme activities exhibited similar mobilities in isoelectric focusing gels, with a pI of 6.1. Thus, although particulate guanylate cyclase from lung presumably possesses receptor binding activity, it is physically identical to a form of this enzyme associated with no measurable binding activity. Possible explanations for these observations are discussed. PMID- 2575209 TI - Two nearby sites bind zen protein independently. AB - The region upstream from the zerknullt (zen) gene contains three sites that specifically bind the zen protein product of the gene. Evidence for these binding sites was obtained by the filter binding technique and the DNase footprinting technique. The filter binding technique was used to scan various segments of DNA for the presence of possible specific binding sites. Segments that were selectively retained by the filter binding technique invariably contained one or more specific binding sites according to the DNase footprinting technique. Two of the zen protein binding sites were spaced only 30 base pairs apart. These sites could be separated without any loss in their specific binding properties. It is concluded that these two sites function independently in the binding of zen protein. PMID- 2575210 TI - [Specific interaction of a nuclear protein factor from the CTF/NF-I family with 2 different promoter regions of the rat tyrosine aminotransferase gene]. AB - Using gel-retardation and DNase I footprinting assays, we have analysed sequence specific DNA-protein interactions within proximal promoter fragment (from -2 to 210 bp relative to the transcription start) of the rat tyrosine aminotransferase (TAT) gene. Two distinct DNase I protection regions flanked at either boundary by sites of DNase I hypersensitivity were observed with the rat-liver nuclear extracts. The internal sequence of the region I non-coding strand, ( 155)TGGGCCACCTTCCAAT(-170), is highly homologous to the NF-I consensus sequence TGG(N)6-7TGCCAA and also shares a CCAAT-box; the region II noncoding strand sequence includes asymmetrically positioned (-37)AGCCAAT(-43) recognition motif. Since there have been a number of reports about multiple DNA-binding factors that recognize CCAAT homologies, both regions were likely to interact with either a single or distinct factors. Here we show that both region I and II of the TAT gene promoter are binding to the same factor related to the human CTF/NF-I. The evidence for that is based on competition experiments using the DNA fragment containing a synthetic consensus sequence for the NF-I recognition site and on the indistinguishable chromatographic properties of the activity specifically binding to each of three DNA fragments containing NF-I consensus, region I and region II sequences. PMID- 2575211 TI - [Nuclear factor A5 from the rat liver that requires a metal for specific interaction in vitro with distal element of the tyrosine aminotransferase gene promoter]. AB - To detect nuclear protein factors which might account for a tissue-specific and inducible expression of the rat tyrosine aminotransferase (TAT) gene promoter, extracts from rat liver and spleen nuclei have been fractionated by heparin sepharose chromatography and the fractions assayed for sequence-specific binding to the distal TAT gene promoter element (sequence between -313 and -210). Gel retardation experiments carried out in the presence or absence of Mg2+, Ca2+, or Zn2+ ions showed that there are at least two nuclear factors (A3 and A4) binding to the distal promoter element only in the presence of the chelator (20 mM EDTA). Incubation of the protein fractions with Zn2+ or Ca2+ instead of commonly used Mg2+allowed: (i) to avoid 3 2P-DNA-probe degradation by "contaminating" endogenous nucleases; and (ii) to detect another sequence-specific nuclear factor, A5. No other specific binding activities were found in the rat-liver nuclear fractions tested under these conditions. As the metal ions became inaccessible to chelation in excess of EDTA and EGTA when protein factor A5 was complexed to DNA we assumed that factor A5 is metalloprotein which requires Zn or Ca to maintain a structure of its DNA-binding domain. To identify the polypeptide possessing this domain, a protein gel blotting procedure was employed. By incubating gel blots with the 3 2P-DNA-probe in the buffer containing Zn2+, specific binding to the only polypeptide with approximate Mr 30 kDa was clearly revealed. Both gel retardation and gel blotting assays consistently showed that nuclear factor A5 is present in the liver, but not in the spleen extracts. PMID- 2575212 TI - Retrovirus-mediated expression of preprosomatostatin in rat pituitary GH3 cells: targeting of somatostatin to the regulated secretory pathway. AB - Somatostatin (SRIF) is a 14-amino acid peptide hormone that is synthesized as part of a larger precursor, prepro-SRIF, consisting of a signal peptide and a proregion of 80-90 amino acids; mature SRIF is located at the carboxyl-terminus of the precursor. We have used a recombinant retroviral expression vector encoding anglerfish prepor-SRIF-I to infect rat pituitary GH3 cells. The aim of these studies was to investigate the intracellular storage and secretion of the total pool of endogenous GH compared to that of SRIF. Several clonal lines of GH3 cells expressing high or low levels of SRIF were treated with TRH, forskolin, or depolarizing concentrations of potassium, and the levels of intracellular and secreted GH or SRIF were determined using highly sensitive RIAs. Approximately 65% of the total GH was secreted basally, whereas less than 20% of the SRIF immunoreactive material was basally secreted. Forskolin treatment or potassium depolarization stimulated GH release, but only about 50% above basal levels. In contrast, SRIF secretion was stimulated approximately 5-fold in response to these secretagogues. Based on its lower basal rate of secretion compared to GH and its enhanced release in response to a variety of secretagogues, we conclude that the heterologously expressed SRIF is preferentially targeted to the regulated pathway in GH3 cells. PMID- 2575213 TI - Regulation of tyrosine aminotransferase by insulin and cyclic AMP: similar effects on activity but opposite effects on transcription. AB - Tyrosine aminotransferase (TAT) is a liver-specific enzyme whose activity is subject to positive regulation by several agents including insulin and agonists that increase the intracellular concentration of cAMP. To further characterize the mechanism of insulin action and the interaction between cAMP and insulin several types of experiments were performed in a rat hepatoma cell-line. In the presence of the transcriptional inhibitor 5,6-dichloro-1-beta-D ribofuranoyslbenzimidazole, TAT enzyme activity remains inducible by insulin and to a lesser extent by the cAMP analog (Bu)2cAMP. This suggests that transcriptional events are not necessary for the insulin-mediated increase in TAT activity, and also suggests a dualistic mechanism for the cAMP-induced increase in TAT activity. Surprisingly, using a cDNA probe for mRNATAT, it was found that insulin causes a decrease in hybridizable mRNATAT, in addition to causing a partial inhibition of the increase of hybridizable TAT transcript caused by (Bu)2cAMP. Examination of the rate of transcription of the TAT gene by a nuclear run-off assay shows that insulin causes a decrease in the transcription of the TAT gene by greater than 50%, which is sufficient to account for the decrease in hybridizable mRNATAT. As expected (Bu)2cAMP increases the transcription of TAT, but combined with insulin a complete inhibition of the increase in TAT transcription caused by (Bu)2cAMP is observed. To address the possibility that insulin acts posttranslationally to increase TAT activity, the t1/2 of TAT protein was measured in the presence and absence of insulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575214 TI - Molecular cloning and characterization of a progesterone-dependent cat endometrial secretory protein complementary deoxyribonucleic acid. AB - In the cat, a group of low molecular weight secretory proteins have previously been shown to appear in the endometrium after progesterone (P) administration to an estrogen (E2)-primed animal. Using a polyclonal antibody to these progesterone dependent proteins (PDP) we have isolated a recombinant cDNA clone corresponding to the mRNA for PDP from a cDNA library prepared using poly(A+) RNA from the endometrium of P-treated E2-primed cats. Comparison of Western blots using the polyclonal antibody and epitope selected antibody demonstrated that the multiple molecular weight and isoelectric forms of the PDP are immunologically related and potentially products of the same gene. Northern analysis revealed that the mRNA for the PDP in the endometrium of P-treated E2-primed cats was 1.8 kilobases in length. Using slot blot analysis, we found that the PDP mRNA levels were low in the endometrium of ovariectomized animals and undetectable in E2-treated animals. With 1 day of P treatment the PDP mRNA levels were readily detectable and they peaked after 5 to 7 days of P treatment. No PDP mRNA was detectable in myometrium, oviduct, or ovary. Sequence analysis revealed that PDP had significant homology to human, rat, and mouse cathepsin L at the nucleotide (80%, 74%, and 73%, respectively) and amino acid (68%, 65%, and 63%, respectively) level. We suggest that PDP via its collagenolytic and elastolytic activities as a cathepsin L is responsible for preparing the endometrium for blastocyst implantation. PMID- 2575215 TI - Expression and posttranslational processing of preprodynorphin complementary DNA in the mouse anterior pituitary cell line AtT-20. AB - A recombinant plasmid containing the rat prodynorphin cDNA was introduced into the mouse anterior pituitary corticotroph cell line AtT-20. These cells normally express and posttranslationally process proopiomelanocortin, but not prodynorphin. Stable transformants were isolated and analyzed for the expression and processing of prodynorphin. The stably transformed AtT-20 cells that expressed a 1.3-kilobase prodynorphin mRNA also expressed prodynorphin protein and processed it to dynorphin peptides. The peptides included leucine-enkephalin, beta-neoendorphin, dynorphin-A8, and dynorphin-B, as identified by gel filtration and reverse phase HPLC followed by RIA using peptide-specific antisera. These results demonstrate that AtT-20 cells efficiently and accurately process prodynorphin at both dibasic sites and monobasic cleavage sites, indicating that the AtT-20 cells contain enzymes capable of cleaving the precursor not only at dibasic residues but also at monobasic residues. The release of prodynorphin derived peptides paralleled secretion of endogenous proopiomelanocortin-derived peptides when stimulated by CRF, a natural secretagogue for ACTH. PMID- 2575216 TI - Activin B: precursor sequences, genomic structure and in vitro activities. AB - We report here the complete amino acid sequence of the human inhibin beta B subunit as deduced from the sequence of cDNA and genomic clones. The primary translation product of the beta B mRNA predicts a protein of 407 amino acids, containing a prepro region of 292 amino acids separated by basic amino acids from the mature C-terminal 115 amino acids. Mammalian tissue culture cells transfected with a beta B-subunit expression plasmid secreted an activin B homodimer of approximately 22K mol wt. Coexpression of the beta A- and beta B-subunit mRNAs resulted in the secretion of the three forms of activin, A, AB, and B. Purified activin B was shown to elicit FSH release in an in vitro pituitary assay and trigger the accumulation of hemoglobin in K562 cells. The potency of activin B in both of these assays (ED50 approximately 2 ng/ml) was indistinguishable from that observed for activin A. PMID- 2575217 TI - Tissue specific expression of rat peptidylglycine alpha-amidating monooxygenase activity and mRNA. AB - The tissue specific expression of peptidylglycine alpha-amidating monooxygenase [(PAM) EC 1.14.17.3], an enzyme which catalyzes the formation of amidated bioactive peptides from their glycine-extended precursors, was examined in adult rat. Soluble and membrane-associated PAM enzymatic activities were determined, and the levels and size classes of PAM mRNA were examined by Northern blot analysis. PAM specific activity varied 1000-fold in the tissues examined, with highest levels in heart atrium, pituitary and salivary glands, and hypothalamus. The fraction of total PAM activity that was membrane associated varied from approximately 70% in heart atrium to 10% in neurointermediate pituitary lobe and thyroid gland. Levels of PAM mRNA varied over 300-fold. In the heart atrium, PAM mRNA accounts for more than 0.1% of the mRNA. For many tissues the ratio of total PAM specific activity to PAM mRNA levels was similar; however, PAM activity was higher than expected from mRNA levels in the salivary glands and lower than expected in several tissues, including heart ventricle. Three major size classes of PAM mRNA were identified among the tissues. Use of RNAse H indicated that differences in size were not due to the length of the poly(A) tail. The heart and central nervous system expressed PAM mRNA of the 4.2 kilobase (kb) and 3.8 kb size classes, while the remaining tissues expressed predominantly 3.8 kb and 3.6 kb classes; few tissues contained only one size class of PAM mRNA. The two major forms of PAM mRNA in adult heart atrium differ by the presence or absence of a 315 nucleotide segment in the protein coding region. Using a cDNA probe from within this segment, the 4.2 kb and 3.8 kb size classes of PAM mRNA in the central nervous system appeared to resemble those in the heart atrium. In the remaining tissues, a subset of PAM mRNAs in the 3.8 kb and 3.6 kb size classes hybridized with this probe, suggesting that additional forms of PAM mRNA are present. PMID- 2575218 TI - Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and differences in liver 1A2 mRNA expression. AB - We have sequenced the human CYP1A2 (cytochrome P(3)450) gene, 1,906 basepairs (bp) of the 5' flanking region, and 113 bp of the 3' flanking region. The gene spans almost 7.8 kilobases, comprising seven exons and six introns. The transcriptional start site was determined by both primer extension and S1 mapping. Including the first noncoding exon of 55 bp, the entire mRNA is 3,121 bp in length, and the open reading frame, starting with nucleotide 10 of exon 2, encodes 515 amino acids (mol wt = 58,294). Between the human CYP1A2 and CYP1A1 (cytochrome P(1)450) genes, exons 2, 4, 6, and especially 5 are strikingly conserved in both nucleotide similarity and total number of bases. Alignment of the upstream sequences and exon 1 of human CYP1A2 with that of mouse or rat CYP1A2 revealed two possibly significant regions of similarity: 1) 68% in the approximately 150 bases immediately 5' from the mRNA cap site and 2) 80% identify between the human -841 to -758 segment and the mouse -1,529 to -1,439 segment. The canonical 5-bp box (CACGC), found upstream of all mammalian CYP1A1 genes to date and believed to interact with the inducer.aromatic hydrocarbon receptor complex, was not found on either strand in the 1,906 bp of the 5' flanking region of human CYP1A2. In contrast, alignment of the upstream sequences, exon 1, and intron 1 of human CYP1A1 with that of mouse or rat CYP1A1 revealed large, highly conserved regions. Conserved regions were found in intron 1 of the human, mouse, and rat CYP1A2 gene. These data suggest that the regulatory elements controlling the CYP1A2 gene might differ in location from those controlling the CYP1A1 gene. Among 12 human liver samples, striking differences (greater than 15-fold) in the 3.3-kilobase 1A2 mRNA levels were seen. This result may reflect significant genetic differences in constitutive and/or inducible CYP1A2 gene expression that could play an important role in individual risk of environmental toxicity or cancer. PMID- 2575219 TI - Tyrosine hydroxylase mRNA in the neurons of the tuberoinfundibular region and zona incerta examined after gonadal steroid hormone treatment. AB - The dopamine-producing neurons of the tuberoinfundibular region are known targets of estrogen and progesterone, and are of considerable neuroendocrine importance. To determine the anatomical distribution, and number of cells that contain tyrosine hydroxylase (TH) mRNA in the tuberoinfundibular region and other regions of the brain we carried out in situ hybridization on sections prepared from ovariectomized female rats given either oil vehicle, or estrogen, or estrogen plus progesterone. The intensity of label per cell was assessed to compare the relative amount of mRNA found per cell among TH-mRNA containing cells. [3H]cRNA probes to the rat TH sequence were used. Autoradiograms demonstrated the presence of TH-mRNA in the cytoplasm of cells in the arcuate and periventricular nuclei, zona incerta, substantia nigra, and the adrenal medulla. The number and anatomical distribution of cells that contained TH-mRNA was identical to the number and distribution of cells previously demonstrated by others to contain TH immunoreactivity. In the arcuate and periventricular nuclei, compared to treatment with estrogen alone, estrogen plus progesterone did lead to a statistically significant decrease in the number of TH mRNA-containing cells we could detect. No alteration in the mean number of grains per cell, among cells detected as containing TH-mRNA was found in any group. In contrast, these same hormone treatments had no effect on the number TH-mRNa producing cells we could detect in the zona incerta. Most of the cells in the zona incerta are found within the same tissue sections as arcuate/periventricular cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575221 TI - Structure and evolution of mouse interleukin 6 gene. AB - Restriction fragment length polymorphism in the interleukin 6 gene of murine rodents extending phylogenetically from Mus musculus domesticus to the rat has been analyzed. Most species exhibit distinct restriction site patterns. In contrast, limited polymorphism was found in the tumor necrosis factor alpha gene indicating different selective pressure acting on both genes. The gene encoding interleukin 6 was isolated from a genomic library and the exon/intron organization was determined by restriction analysis and limited DNA sequence analysis. It consists of five exons which distribute over about seven kilobases, thus resembling in structure and organization the human counterpart. Furthermore, no restriction fragment length polymorphisms in the interleukin 6 gene of autoimmune strains NZB, NZW, MRL-lpr/lpr and BxSB could be detected for either EcoRI, BamHI or HindIII. PMID- 2575220 TI - Sequence and chromosomal assignment of a novel cDNA identified by immunoscreening of a thyroid expression library: similarity to a family of mitochondrial solute carrier proteins. AB - An immunoglobulin G (IgG) preparation of the serum from a patient with active Graves' disease was used to isolate cDNA clones from a lambda gt11 cDNA library of human thyroid follicular carcinoma tissue by immunoscreening. One of these clones, hML-7, is further characterized herein by sequencing, Northern analysis, and chromosomal mapping. The clone reacted with IgG preparations from the sera of 14 of 19 patients with active Graves' disease but not with IgG preparations from 11 normal individuals, three patients with toxic thyroid adenoma, and three with rheumatoid arthritis. The hML-7 cDNA hybridized to a 3.6 kilobase (kb) mRNA transcript in poly(A+) RNA preparations from human thyroid tissue and continuously cultured rat thyroid cells; expression of this transcript in rat FRTL-5 thyroid cells was positively regulated by TSH. The 3.6 kb transcript was less abundant in rat liver (BRL3A) cells or differentiated rat (L6) myoblasts than in cultured rat thyroid cells and was not detectable in mouse L-M fibroblasts, human IM-9 lymphocytes, Chinese hamster ovary cells, or human cervical carcinoma cells. The cDNA from hML-7 was sequenced and compared with the sequence of cross-hybridizing cDNA clones isolated from human Graves' thyroid and rat FRTL-5 thyroid cell lambda gt11 expression libraries. A 1.05 kb open reading frame, which is highly conserved between human and rat, was defined. The predicted amino acid sequence of 348 residues exhibited a strong homology with the mitochondrial ADP/ATP carrier protein (adenine nucleotide translocase; ADP/ATP translocator) and with two other members of the same mitochondrial protein family, the phosphate carrier and the hydrogen ion uncoupling protein. The gene represented by the hML-7 cDNA has been assigned to human chromosome 10. PMID- 2575222 TI - Genetic evidence that metacyclic forms of Trypanosoma brucei are diploid. AB - The hypothesis that metacyclic trypanosomes are haploid has been tested genetically. Five cloned stocks of Trypanosoma brucei (each having four known isoenzyme markers and six known restriction fragment length polymorphisms) have been independently transmitted through tsetse flies. Fifteen individual metacyclic organisms were taken from flies with mature cyclical infections and used to establish fresh clones. All the sub-clones from all the flies proved to be identical to the starting (parental) stocks, with respect to all the markers examined, including those markers which were heterozygous in the parental stocks. We conclude that metacyclic trypanosomes are diploid, and are not the product of an obligatory meiosis. PMID- 2575223 TI - Structure-activity relationships of MDMA-like substances. PMID- 2575224 TI - Acute and long-term neurochemical effects of methylenedioxymethamphetamine in the rat. PMID- 2575225 TI - Effects of MDMA and MDA on brain serotonin neurons: evidence from neurochemical and autoradiographic studies. AB - The data presented in this chapter provide strong evidence, from both neurochemical and neuroanatomical studies, demonstrating that, following in vivo administration of a number of methylenedioxy-substituted amphetamine derivatives, there is widespread and long-lasting degeneration of serotonin neurons in brain, without any major or consistent effects on catecholamine neurons. A detailed examination of the parameters involved in the neurotoxic and neurodegenerative effects of MDMA on brain serotonin neurons indicates that: (1) the severity of the lesion by MDMA is dependent on both the dose and frequency of drug administration; (2) the neurodegenerative effects of MDMA can be elicited in a number of animal species including primates; (3) the neurodegenerative effects on brain serotonin neurons can be prevented by the serotonin uptake blocker, suggesting a role for the active uptake of MDMA, a neurotoxic metabolite of MDMA, or an unidentified endogenous neurotoxin; and (4) the neurodegenerative effects of the drug are long-lasting (up to 1 year) with respect to neuronal recovery, while functional recovery may be permanently impaired. In addition, the neurochemical and autoradiographic data suggest that there is some neuroanatomical and morphological specificity to the neurodegenerative effects of MDMA and MDA, as evidenced by predominant reductions in serotonin uptake sites in brain regions containing primarily serotonin terminals, while regions containing serotonin axons of passage and cell bodies are relatively unaffected. PMID- 2575226 TI - Characterization of brain interactions with methylenedioxyamphetamine and methylenedioxymethamphetamine. AB - Brain recognition sites have been identified for [3H]MDA and [3H]MDMA. The dissociation constants of MDA and MDMA for these sites are similar to the concentrations needed to affect several brain neurochemical parameters and are in keeping with concentrations of MDA in brain (165 microM) following administration of behaviorally active doses (20 mg/kg) of the drug. While the characteristics of these binding sites suggest a possible hydrophobic interaction with brain membranes, this interaction is not without specificity, since it has a unique pharmacology and a heterogeneous distribution in brain. Similarities have been found between [3H]MDA binding studied in the present report and that of apparent [3H](+)amphetamine binding studied by Hauger et al. (1984). Both have extremely high Bmax values, are optimal in p2 preparations, are stabilized by sucrose, and share similar patterns of regional distribution. Measuring the specific binding of [3H]amphetamine, [3H]fenfluramine, [3H]MDA, and related compounds under identical conditions will be required to determine the possible relationships among the interactions of these compounds with brain membranes. Further study is also needed to determine the possible importance such interactions of amphetamine and its substituted analogs may have with brain membranes in relation to the pharmacology of these substances. PMID- 2575227 TI - Studies of MDMA-induced neurotoxicity in nonhuman primates: a basis for evaluating long-term effects in humans. AB - The results of the studies reviewed here show that the neurotoxic effects of MDMA generalize to the primate. Further, they indicate that monkeys are considerably more sensitive than rats to the serotonin-depleting effects of MDMA, and that the dose-response curve of MDMA in the monkey is much steeper than in the rat. Perhaps as a consequence of this, the toxic effects of MDMA in the monkey involve serotonergic nerve fibers as well as cell bodies, whereas in the rat, only nerve fibers are affected. The present studies also show that the toxic dose of MDMA in the monkey (5 mg/kg) closely approaches the dose typically used by humans (1.7 to 2.7 mg/kg). This finding heightens concern that MDMA may be neurotoxic in humans, particularly since the steepness of the dose-response curve of MDMA in the primate suggests a narrow margin of safety. Finally, preclinical studies in monkeys have shown that CSF 5-HIAA can be used to detect MDMA-induced serotonergic damage in the primate CNS. Studies now underway in MDMA-exposed humans should help determine if MDMA exerts long-term toxic effects on serotonergic neurons in the human brain. PMID- 2575228 TI - Dose- and time-dependent effects of stimulants. PMID- 2575229 TI - Stimulus properties of hallucinogenic phenalkylamines and related designer drugs: formulation of structure-activity relationships. PMID- 2575230 TI - [The role of drug therapy in the treatment of obsessive-compulsive disorders]. PMID- 2575231 TI - [Neuroleptic-induced akathisia]. PMID- 2575232 TI - Development of monoamine oxidase activity and monoamine effects on glutamate release in cerebellar neurons and astrocytes. AB - Activities of monoamine oxidase (MAO) A and B were measured during the first month of postnatal development in mouse cerebellum and in primary cultures of either cerebellar granule cells or cerebellar astrocytes, derived from 7-day-old cerebella. In addition, effects of the two monoamines, serotonin (a MAO A substrate) and phenylethylamine (a MAO B substrate) on the release of glutamate under resting conditions and in a transmitter related fashion (i.e., potassium induced, calcium-dependent glutamate release) were studied during the same period. Both MAO A and MAO B activities increased during in vivo development (beginning around postnatal day 14) and in cultured astrocytes (during a comparable time period and to a similar extent), but remained constant at a low level in granule cells. In 4-day-old cerebellar granule cell cultures there was no potassium-induced glutamate release but serotonin as well as phenylethylamine reduced the release in both the presence and absence of excess potassium. In 8- and 12-day-old granule cell cultures and in 8- and 18-day old astrocyte cultures there was a pronounced glutamate release during superfusion with 50 mM K+. In both neurons and astrocytes this response was inhibited by 1 nM of either serotonin or phenylethylamine. In the astrocytes the inhibition was followed by an increased release of glutamate in both the presence and absence of the high potassium concentration, whereas the 8-day-old neurons showed only a slight increase in glutamate release after the withdrawal of the monoamine and only in the absence of excess potassium. The response was almost identical in 8- and 18 day-old astrocytes in spite of the marked difference in MAO activities. PMID- 2575233 TI - Early and late passage C-6 glial cell growth: similarities with primary glial cells in culture. AB - Earlier studies in our laboratory have shown that C-6 glial cells in culture exhibit astrocytic properties with increasing cell passage. In this study, we tested the responsiveness of early and late passage C-6 glial cells to various cultures conditions: culture substrata (collagen, poly-L-lysine, plastic), or supplements for the culture medium, DMEM, [fetal calf, or heat inactivated (HI) serum, or media conditioned from mouse neuroblastoma cells (NBCM) or primary chick embryo cultured neurons (NCM)]. Glutamine synthetase (GS) and cyclic nucleotide phosphohydrolase (CNP), astrocytic and oligodendrocytic glial markers, were used. Cell number and protein content increased exponentially with days in culture regardless of the type of the substratum or cell passage. Differences in cell morphology among the three types of substratum were also reflected on GS activity, which rose by three-fold on culture day 3 for cells grown on collagen; thereafter, GS profiles were similar for all substrata. This early rise in GS is interpreted to reflect differential cell adhesion processes on the substrata; specifically, cell adhesion on the collagen stimulated differentiation into "astrocytic phenotype". Analogous to immature glia cells in primary cultures, early passage C-6 glial cells responded to neuronal factors supplied either from NCM or NBCM by expressing reduced GS activity, the astrocytic marker and enhanced CNP activity, the oligodendrocytic marker. Thus, early passage cells can be induced to express either astrocytic or oligodendrocytic phenotype. In accordance with our previous reports on primary glial cells, late passage C-6 cells exhibit their usual astrocytic behavior, responding to serum factors with GS activity. Moreover, whereas NCM or NBCM alone markedly lowered GS activity, a combination with serum restored activity. The present findings confirm our previous observations and further establish the C-6 glial cells as a reliable model to study immature glia. PMID- 2575235 TI - Increased pituitary response to somatostatin in aging male rats: relationship to somatostatin receptor number and affinity. AB - Previous research has established that growth hormone pulse amplitude declines with increasing age. The purpose of this study was to determine whether this decline is associated with (1) increased pituitary response to somatostatin, and/or (2) increased number or affinity of pituitary somatostatin receptors. In the first study, pituitary slices from young (3-4 months), middle-aged (12-14 months), and old (22-24 months) male Fischer 344 rats were superfused with minimal essential medium (1 ml/min) and fractions collected at 5-min intervals. Tissues were stimulated with 10(-7) M hpGRF (1-44) for 1 min and, 40 min later, with hpGRF in the presence of 5 x 10(-9) M somatostatin-14 or somatostatin-28. Two pituitaries from each age group were superfused simultaneously and the experiment replicated 4 times. Growth hormone release was measured by radioimmunoassay. In a second study, somatostatin receptors in purified pituitary membranes from the three age groups were compared using iodo-[Tyr0]-D-Trp8 somatostatin-14. Animals from each age group were pooled, membranes extracted, and incubated with increasing doses of cold peptide. Binding characteristics were analyzed by Scatchard analysis and Ka and Bmax calculated. Results indicated that (1) basal growth hormone release diminished both with age and somatostatin administration, (2) GRF-induced release of growth hormone was similar in all age groups when data were expressed as percent increase from baseline, and (3) in the presence of somatostatin-14, GRF-induced release of growth hormone was attenuated in old as compared to young or middle-aged rats (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575236 TI - Regional distribution of immunoreactive somatostatin in the bovine pineal gland. AB - Regional distribution of immunoreactive somatostatin (IRS) and melatonin were investigated in the bovine pineal gland. The total IRS and melatonin content ranged from 0.26 to 2.28 pmol, and from 19.4 to 42.7 pmol, respectively, per bovine pineal. Reverse phase liquid chromatography of pineal extracts demonstrated that more than 90% of IRS coeluted with synthetic somatostatin-14 and somatostatin-28. While the IRS content was shown to vary considerably throughout the gland, with a constant and marked maximal concentration at the proximal end of the pineal, the maximal melatonin concentration appeared in the central part of the gland, coinciding with the total protein distribution. The existence of the highest levels of pineal IRS near the habenular commissure, where the afferent fibers of the central pinealopetal innervation enter the gland, suggests that pineal somatostatin may be, at least in part, of neural origin. PMID- 2575234 TI - Neuronal-glial interactions: quantitation of astrocytic influences on development of catecholamine neurons. AB - Effects of astroglia on the morphological and biochemical differentiation of catecholamine neurons from embryonic rat mesencephalon were studied in vitro, and compared to results obtained with fibroblasts. Neurite outgrowth and complexity were measured using computer-assisted morphometry on tyrosine hydroxylase immunoreactive neurons growing on preformed monolayers of astrocytes or fibroblasts. The morphological differentiation of these neurons was stimulated by the presence of astrocytes, and this effect was evident in various cellular compartments, including the size of the cell soma, length of neurites and neuritic segments, and the numbers of these segments. Tyrosine hydroxylase activity was measured biochemically in these cultures and was also found to be stimulated by the presence of astroglial monolayers. The implication of these results for the understanding of specific neuron-glial interactions during embryonic brain development is discussed. PMID- 2575237 TI - Hypothalamic interconnections of somatostatin and growth hormone releasing factor neurons. AB - Combined immunohistochemical labelling for neurons containing growth hormone (GH) releasing factor (GRF) or somatostatin and single labelling immunohistochemistry combined with Fluorogold retrograde transport labelling were used to examine whether somatostatin or GRF neurons might be reciprocally innervated. Occasional somatostatin-immunoreactive neurons in the periventricular preoptic area were found to be closely approached by GRF-immunoreactive fibres, providing possible evidence of scant innervation of somatostatin neurons by GRF cells. In contrast, many GRF-immunoreactive neurons in the arcuate nucleus appeared to have somatostatin-immunoreactive fibres closely applied to their perikarya suggesting that GRF neurons might be innervated by somatostatin cells. Combined retrograde tracing and fluorescence immunohistochemistry revealed few somatostatin immunoreactive neurons doubly labelled following injections of Fluorogold in the basal hypothalamus. Occasional GRF-immunoreactive neurons in the basal hypothalamus were doubly labelled following PO/AHA injections of Fluorogold. Numerous somatostatin-immunoractive perikarya were observed in the periventricular arcuate region in colchicine-pretreated animals. We conclude that GH-regulating neurons do not have strong reciprocal innervation. The innervation of GRF neurons by somatostatin fibres may be derived from local somatostatin neurons. PMID- 2575238 TI - Intrahypothalamic actions of somatostatin and growth hormone releasing factor on growth hormone secretion. AB - Possible effects of GRF on somatostatin neurons and of somatostatin on GRF neurons were examined by measuring the effects of localised intracerebral injections of these peptides on growth hormone (GH) secretion. Serial GH concentrations were measured in plasma in unanaesthetized male rats chronically prepared with venous and intracerebral cannulae, before and after treatment with bilateral intracerebral injections of somatostatin or GRF in the preoptic anterior hypothalamic area (PO/AHA) and medial basal hypothalamus. Injections of 0.1 and 1 nmol of GRF in medial basal hypothalamus or 10 nmol somatostatin in the PO/AHA, respectively, had stimulatory or inhibitory effects on GH, which were assumed to be due to diffusion of the peptide from the injection site to the median eminence and pituitary gland. Injection of lower doses of somatostatin around GRF neurons in the medial basal hypothalamus were without significant effect on secretion of GH, but 0.1 nmol somatostatin in the PO/AHA resulted in an increase in GH concentrations from 128 +/- 61 to 524 +/- 103 ng/ml, p less than 0.02. Injections of GRF in lower doses amongst somatostatin neurons in the PO/AH or amongst GRF neurons in the medial basal hypothalamus were both without effect on GH secretion. We conclude that somatostatin may stimulate GH secretion by an effect on or close to somatostatin neurons in the PO/AHA. Somatostatin, though present in terminals on GRF neurons, is without effect at this site in our model. Furthermore, we have been unable to demonstrate any significant intrahypothalamic effect of GRF on GH regulation. PMID- 2575239 TI - Analysis of a genetic cross between Trypanosoma brucei rhodesiense and T. b. brucei. AB - Two trypanosome clones, representing East and West African homozygotes at 2 isoenzyme loci (T. b. rhodesiense MHOM/ZM/74/58 [CLONE B] and T. b. brucei MSUS/CI/78/TSW 196 [CLONE A]), were cotransmitted through tsetse flies and the resulting trypanosome populations checked for the presence of non-parental karyotypes by pulsed-field gel electrophoresis. Ten clones isolated from these populations proved to have 5 different recombinant genotypes by analysis of nuclear and kinetoplast DNA (kDNA) polymorphisms. It is inferred that genetic exchange occurred between the 2 trypanosome clones in the fly, as previously reported for 2 other T. brucei spp. clones by Jenni and colleagues. For the most part, the hybrid clones shared many characteristics with both parents and their genotypes were consistent with segregation and reassortment of parental alleles. The least amount of genetic material exchanged was kDNA alone. Regarding the mechanism of genetic exchange, several hybrid clones had identical and unique nuclear DNA polymorphisms, but different kDNA type. Assuming that the same reassortment of nuclear markers is unlikely to occur by chance, these clones most probably arose from a predecessor carrying both types of kDNA. PMID- 2575240 TI - Mapping of the gene for multiple endocrine neoplasia type I to chromosome 11q13. PMID- 2575241 TI - Gene polymorphism and cancer susceptibility. PMID- 2575242 TI - [Current methods of treatment of cryptorchism]. PMID- 2575243 TI - [Functional growth retardation and its correction]. PMID- 2575244 TI - dNTP imbalance and DNA double strand breaks in mouse FM3A cells and the mechanism of cell death. AB - The mechanism of intracellular deoxyribonucleoside-triphosphate (dNTP) imbalance death of mouse mammary tumor FM3A cells was studied. When the cells were exposed to 5-fluorodeoxyuridine, deoxyadenosine, or 2-chlorodeoxyadenosine, dNTP pool imbalance resulted. The imbalance was followed by DNA double-strand breaks and subsequent cell death. The DNA double strand breaks were directly examined by means of orthogonal-field-alternation gel electrophoresis (OFAGE). Fragmented DNA band appeared to be approximately 100-200 kbp in size. The bases of 5'-termini in the DNA were cytosine and thymine. The imbalance induced endonuclease has been isolated by DEAE-agarose column chromatography. PMID- 2575245 TI - A polymorphic DNA marker genetically linked to congenital malformations. AB - Unusual restriction fragments were detected by DNA blot hybridization with PCNA (DNA polymerase-delta auxiliary protein) probe in one of seven cases of congenital malformations. Chromosomal in situ hybridization localized PCNA gene to region q31-35 of human chromosome 2. To discover the locus more closely associated with congenital malformations, a cloned DNA segment which has been mapped to chromosomal region 2q33-36 was tested for restriction fragment length polymorphisms (RFLPs) in these patients. The 2q33-36 probe hybridized with 2.1 kb, 1.9-kb and 1.7-kb fragments in ten normal control samples. In seven cases of congenital malformations examined, however, the band of 2.1 kb is absent in six cases and the band of 1.7 kb in one case. These results indicate that the locus closely linked to congenital malformations is present in the proximity of PCNA locus. PMID- 2575246 TI - Stability of CAT gene transcript depends on the 3'-end structure. AB - To determine the involvement of 3'-end structure of mRNA in the regulation of gene expression in eukaryotic cell, a series of pSCAT plasmids was constructed with chloramphenicol acetyltransferase (CAT) gene and the 3'-regulatory elements from various eukaryotic genes. As a result of determination of the CAT activities and the mRNA level generated from these plasmids, both results were well correlated. Furthermore, the treatment of transfected cells with phorbol ester (TPA) revealed that the polyadenylated CAT mRNAs form some genes were stabilized, in contrast, the mRNAs bearing 3'-end structure of histone or C-myc genes were not. PMID- 2575247 TI - Neuropeptide-hydrolysing activities in synaptosomal fractions from dog ileum myenteric, deep muscular and submucous plexi. Their participation in neurotensin inactivation. AB - The mapping of neuropeptidases in synaptosomal fractions prepared from dog ileum myenteric, deep muscular and submucous plexus was established by means of fluorigenic substrates and specific inhibitors. Endopeptidase 24.11, angiotensin converting enzyme and aminopeptidases were found in all tissues, the highest amounts being recovered in the submucous preparation. Post-proline dipeptidyl aminopeptidase was obtained in high quantities whatever the tissue source while proline endopeptidase was detected in low amounts and pyroglutamyl-peptide hydrolase was never detectable. The above peptidases were examined for their putative participation in the inactivation of neurotensin by monitoring the effect of specific inhibitors on the formation of the metabolites of labeled neurotensin separated by HPLC. Endopeptidases 24.11, 24.15 and 24.16 were respectively responsible for the formation of neurotensin(1-11), neurotensin(1-8) and neurotensin(1-10) that are devoid of biological activity. The secondary attacks occurring on neurotensin degradation products were the following: cleavage of neurotensin(1-10) into neurotensin(1-8) by angiotensin-converting enzyme; conversion of neurotensin(9-13) into neurotensin(11-13) by post-proline dipeptidyl aminopeptidase; hydrolysis of neurotensin(11-13) into free tyrosine by aminopeptidase(s). PMID- 2575248 TI - Modulation of a 190-kD microtubule-associated protein in pigment epithelium by VIP. AB - Vasoactive intestinal peptide stimulates phosphorylation of six high molecular weight cytosolic proteins in the cultured retinal pigment epithelium (RPE). Of these, the 190-kD phosphoprotein is associated with the microtubules assembled by taxol/GTP and is immunologically related to the brain microtubule-associated protein 2 (mol.wt. = 280 kD). VIP is also shown here to stimulate secretion in the cultured RPE. VIP-stimulated phosphorylation of a 190-kD microtubule associated protein is also demonstrated here in the retinal glia. PMID- 2575250 TI - Emergency dental care. AB - Health care workers in any setting who deal with children should have a basic understanding of the management of dental emergencies. Immediate action is required to reimplant the avulsed permanent tooth while primary teeth are not reimplanted. Dental infections are usually due to pulpal pathosis secondary to caries or trauma. They are managed like any other infection using drainage, antibiotics and removal of the source. PMID- 2575249 TI - Somatostatin-immunoreactive nerve fibers in close association with capillaries in the small intestine. AB - Electron microscopic immunocytochemistry was used to identify somatostatin immunoreactive nerve profiles around the capillary system of the small intestine in the rat and cat. The highest density of somatostatin-immunoreactive nerve profiles was seen in the mucosa, and 25-30% of all immunoreactive profiles were found immediately adjacent to the endothelial cells of capillary blood vessels. About half of the capillary endothelial cells were fenestrated. The majority of the immunoreactive nerve profiles were varicosities, containing synaptic vesicles. These observations suggest that somatostatin might be released from varicose nerve fibers and may contribute to the elevated levels of the peptide measured in portal blood as compared to peripheral blood. PMID- 2575251 TI - Orofacial signs of child abuse and neglect: a dental perspective. AB - Fifty percent of all physical injuries resulting from child abuse involve the head and neck, with trauma to the head being the most frequent cause of death. Health professionals can assume a primary role in detecting and reporting child abuse and neglect through awareness of the most prevalent orofacial signs and symptoms of this problem. PMID- 2575252 TI - Use of somatostatin in the management of pancreatic haemobilia. AB - An elderly man, not previously known to have chronic pancreatitis, presented with haematemesis and melaena which was endoscopically diagnosed as haemobilia. Retrograde cholangiopancreatography showed blood clot in both the common bile duct and the pancreatic duct and the computed tomographic scan appearances were those of gross calcific chronic pancreatitis. Despite active bleeding, it was not possible to demonstrate its source at angiography, thus precluding therapeutic embolization. Thirty six hours after commencing an infusion of somatostatin, repeat endoscopy showed no evidence of active or recent bleeding. The infusion was continued for 5 days during which time he had no further bleeding. PMID- 2575253 TI - Perirenal and renal subcapsular haematoma as presenting symptoms of polyarteritis nodosa. AB - Two young men, were hospitalized due to acute massive blood loss with left abdominal flank pain. In both cases renal angiography showed signs of a haemorrhagic event in the left kidney, perirenal in one and subcapsular in the other. Microaneurysms indicated a diagnosis of polyarteritis nodosa, supported by renal biopsy in one case. Renal haemorrhage is an infrequent presentation of polyarteritis nodosa. Furthermore, one patient suffered also from familial Mediterranean fever, and is the fifth reported case with this combination of diseases. PMID- 2575254 TI - Growth response to chronic beta agonist feeding and mature carcass characteristics of quail (Coturnix coturnix japonica) selected for high and low body densities. AB - A study was conducted to determine the effect of long-term feeding of a beta agonist (cimaterol) on female Japanese quail. Quail used were from lines selected for high (HD) and low (LD) body density from a randombred population. Dietary treatments consisted of 1) the basal feed, 2) the basal feed containing .5 ppm, or 3) 1.0 ppm of the beta agonist. The treatment period for the six experimental groups extended from 14 to 94 days of age. Weight gains to 49 days and live weights at 94 days of age were greater (P less than .05) in the cimaterol-fed groups. Age and live weight at first egg in both lines were greater (P less than .01) when groups were fed treated diets. Eviscerated carcass yields were higher (P less than .01) and carcass moisture was lower (P less than .05) in treated groups. There were no differences in carcass fat or protein among the dietary treatments. Abdominal fat pad weights were larger (P less than .05) in the heavier (P less than .01) HD line but were not significantly affected by cimaterol. Abdominal adipocyte diameters were significantly larger in HD (P less than .05) and cimaterol-treated (P less than .05) quail. PMID- 2575256 TI - Antiperspirant activity of H1-histamine blockers as determined by a modified rat foot pad assay. AB - A method for inducing sweating in the rat via heat stress and without the use of general anesthetics is presented. Five commonly used H1-blocking antihistamines were evaluated in this model for their antiperspirant efficacy. The antihistamines evaluated and their ED50 values (micrograms base/pad) were as follows: phenindamine, 3.02; diphenhydramine, 3.25; chlorpheniramine, 3.12; tripelennamine, 4.91; and pyrilamine, 13.03. Atropine sulfate, injected into the foot pads, was also found to inhibit the sweat response. The response to atropine varied directly with dose. The ED50 was estimated to be 0.4 ng base/foot pad. No systemic effects or contralateral involvement were seen. The rat foot pad contains eccrine sweat glands that are innervated by sympathetic cholinergic fibers. This relationship is analogous to that in the eccrine sweat glands of man. The rat data suggest that antihistamines, possibly via an anticholinergic effect, may be useful as potential antiperspirants in man. PMID- 2575255 TI - Transdermal delivery of narcotic analgesics: comparative permeabilities of narcotic analgesics through human cadaver skin. AB - Relationships between the in vitro permeation rates of select narcotic analgesics through human skin and their physicochemical properties were investigated by following the permeation kinetics of six representative compounds in small diffusion cells. The relative permeability coefficients of three phenylpiperidine analogues, meperidine, fentanyl, and sufentanil, all measured on a single piece of skin, were 3.7 x 10(-3), 5.6 x 10(-3), and 1.2 x 10(-2) cm/hr, respectively. Using membranes from the same skin section, the permeability coefficients of three opioid alkaloids, morphine, codeine, and hydromorphone, were considerably lower, at 9.3 x 10(-6), 4.9 x 10(-5), and 1.4 x 10(-5) cm/hr, respectively. The high permeability coefficients of the former compounds are due to their highly lipophilic nature as reflected in high octanol/water partition coefficients and low solubility parameters. Generally, the permeability coefficients of the narcotics increase as the lipophilicity increases. When viewed in literature perspective, the data suggest that aqueous tissue control of transport is approached in the case of the phenylpiperidine analogues, all of which have Koctanol/water values greater than 40. Permeability coefficients of fentanyl and sufentanil were also determined as a function of pH over the pH range 7.4 to 9.4, in this instance with membranes prepared from additional samples of skin. The permeability coefficients of each drug varied less than threefold over the pH range, a behavior consistent with the highly hydrophobic natures of the compounds. The low permeability coefficients of morphine, codeine, and hydromorphone coupled with their low potencies make these drugs poor transdermal candidates. It appears that fentanyl and sufentanil can be successfully transdermally delivered. PMID- 2575258 TI - Molecular genetics of ornithine aminotransferase defect in gyrate atrophy. PMID- 2575259 TI - Regulation of fatty acid synthesis via phosphorylation of acetyl-CoA carboxylase. PMID- 2575257 TI - Glial markers in iodoacetate retinal degeneration. PMID- 2575260 TI - Central and peripheral actions of alpha 2-adrenergic agonists on renal function in Long-Evans and Brattleboro rats. AB - The effects of 3 alpha 2-adrenergic receptor agonists on renal function in vasopressin (AVP)-deficient Brattleboro (DI) rats were evaluated. The aim of this study was to determine the relative contribution of central versus peripheral alpha 2-adrenoceptors in mediating diuresis and natriuresis, as well as the role of alpha 2-adrenoceptors in antagonizing the actions of AVP. In addition to the studies of renal function, the effects of AVP deficiency on renal alpha 2 adrenoceptor affinity and number was evalauted along with determination of peripheral catecholamine stores. The centrally acting alpha 2-adrenergic agonists guanabenz and guanfacine significantly increased urine output and sodium excretion in Long-Evans (LE) rats. Guanabenz and guanfacine increased urine output in DI rats but failed to increase sodium excretion. The polar alpha 2 adrenergic agonist, ST-91, increased sodium excretion in both LE and DI rats, however, at a dose of 1.0 mg/kg urine output was significantly decreased in DI rats. The 3 alpha 2-adrenergic agonists increased potassium excretion in LE rats, but at the 1.0-mg/kg dose of guanabenz and ST-91, potassium excretion was significantly inhibited in DI rats. Renal alpha 2-adrenergic receptors and norepinephrine stores were not altered in DI rats. Adrenal NE stores were significantly elevated in DI rats relative to LE rats. The results of this study suggest that in the absence of AVP, centrally acting alpha 2-adrenergic agonists have limited natriuretic action, although peripheral activation of alpha 2 adrenoceptors is sufficient to elicit natriuresis irrespective of the presence of AVP. The chronic deficiency of AVP does not alter renal alpha 2-adrenergic receptor number, but the natriuretic and kaliuretic actions of alpha 2-adrenergic agonists are altered in DI rats. PMID- 2575261 TI - Pediatric urology. AB - Development of the genital and urinary systems is interwoven. Developmental abnormalities may cause problems in both systems, although the presenting problem may be ambiguous genitalia, hypospadias, undescended testis, or a urinary tract infection. The primary care physician must understand the underlying significance of pediatric urologic problems and seek appropriate consultation in a timely manner. PMID- 2575262 TI - Striatal D2 dopaminergic receptor status ascertained in vivo by positron emission tomography and 76Br-bromospiperone in untreated schizophrenics. PMID- 2575263 TI - The frequency of gastrointestinal endocrine tumours in a well-defined population- Northern Ireland 1970-1985. AB - The reported incidence of gastrointestinal endocrine tumours is variable. In Northern Ireland circumstances allowing such an assessment are favourable with a central diagnostic laboratory and register established to collect data on tumours from a well-defined population of 1.5 million people. From 1970 to 1985, 368 cases were recorded of which 85 per cent were carcinoid tumours. The annual incidence of carcinoid tumours was 1.3 per 100,000 of the population and the majority occurred in the appendix (61 per cent). No patients presented with the carcinoid syndrome. The annual incidence for other tumours was 0.12 per 100,000 for insulinomas; islet cell tumours of unknown type 0.07; Zollinger-Ellison syndrome 0.05; and multiple endocrine neoplasia (MEN) 0.05. There were two cases of VIPoma, one glucagonoma, one neurotensinoma and one tumour producing ACTH. It is possible that some tumours are more uncommon than others because of difficulty in diagnosis. PMID- 2575264 TI - [Oligonucleotide-genotyping of the HLA-DRB gene after enzymatic amplification by polymerase chain reaction]. PMID- 2575265 TI - Some observations on the mosquitoes of Indian settlements in Xingu National Park, Mato Grosso State, Brazil, with emphasis on malaria vectors. AB - A mosquito survey was carried out in malarious indian settlements in the Xingu National Park, Brazil, by the end of the rainy season--March, 1987, when 27 species were collected. An. darlingi, the most frequent an anthropophilic mosquito, was found infected with P. falciparum and seems to be the principal malaria vector in the area. The other Anophelinae and Culicinae were little frequent or scarce. The local fauna includes vectors of yellow fever and of several other arbovirus. PMID- 2575266 TI - [Carcinoid of the bronchi and adenoma of the parathyroid: is it a fortuitous association or a multiple endocrine neoplasm?]. PMID- 2575267 TI - [Significance of circulating anti-thyroid stimulating hormone (TSH) receptor antibodies in patients with autoimmune thyroid diseases--thyroid stimulation blocking antibody in patients with Graves' disease]. AB - It is a well-known fact that a thyroid stimulation blocking antibody (TSBAb) may play an important role in primary hypothyroidism. However, it has rarely been reported that TSBAb appears in only a few cases of Graves' disease which became hypothyroidism in their clinical courses. We examined TSBAb in 120 sera from 79 cases with Graves' disease before or while under methimazole (MMI)-treatment. TSBAb value was expressed as the percentage inhibition of TSH-stimulated cAMP response of porcine thyroid cells by the patient's IgG. TSBAb was positive in 9 cases (11.4%) of 79 cases of Graves' disease. In 6 of the 9 cases, TSBAb was detected at the untreated period. In the other 2 of the 9 cases, it was detected during the exacerbation related with their pregnancy. It was difficult to control Graves' disease in all 9 cases. These results suggest that TSBAb appears not only in primary hypothyroidism but also even in the hyperthyroid state of Graves' disease, and that the combination of TSAb and TSBAb may regulate the pathogenesis of Graves' disease. PMID- 2575268 TI - [Drug-induced hepatitis]. AB - Drug-induced hepatitis still arouse many practical problems, as their pathogenesis has not been fully elucidated yet, given the absence of specific criteria. Drug-induced hepatitis are acute and chronic. Cytolytic hepatitis, cholestatic hepatitis and mixed hepatitis belong to the former category. Drug induced hepatitis show various clinical and biological pictures, generally similar to those of viral hepatitis. In the most cases, the prognosis is good and their evolution favourable. Cytolytic hepatitis--the result of a wider hepatocytic necrosis--have a more severe prognosis. The most severe form is the fulminant acute hepatitis, a consequence of the substantial necrosis of the hepatic parenchyma. Chronic hepatitis appears after prolonged administration of some drugs with toxic action. Clinical and biological manifestations are not characteristic. Evolution towards cirrhosis is possible. Drug-induced hepatitis are treated by interruption of the drugs generating them. After removing the noxious agent, the disease resolution takes place in one or two weeks. PMID- 2575269 TI - [Cholecystectomy in asymptomatic gallstones. Indications, opportunities and arguments in favor of surgical intervention]. AB - Asymptomatic biliary lithiasis (discovered accidentally by paraclinical methods or intraoperatively) is, despite its hidden character, a state of disease. Asymptomatic lithiasis--having a frequency of 1.3%-7.5%--requires the use of several therapeutical measures. In this way some severe complications at the onset or at the turning of disease into a clinically manifest suffering, especially after the age of 60-70 years, or concomitantly with other affections, might be avoided. The conservatory therapeutical means have limited indications, or results dependent on several parameters, and some methods require a special equipment. The author pleads for cholecystectomy, which, if no complication appears, offers a radical solution with minimum morbidity and unsignificant postsurgical mortality indices. PMID- 2575270 TI - [Thrombolytic treatment of acute myocardial infarct]. PMID- 2575271 TI - [Arterial hypertension in pregnancy]. PMID- 2575272 TI - [Osteoporosis of the menopause. Therapeutic implications]. PMID- 2575273 TI - [The antipyretic effect of phenylbutazone on neoplasm-induced fever (a simple and original diagnostic test)]. PMID- 2575274 TI - [Acute alcoholic hepatitis]. AB - In a group of 1,025 cases of alcoholic liver the authors detected 28 cases (2.73%) of acute alcoholic hepatitis on the basis of the morphologic examination, 75% were males, mean age 45 +/- 18 years. The mean amount of alcohol consumed daily was 106.7 g for a mean duration of 19.78 years. The hepatic lesional substrate was hepatic steatosis and cirrhosis in 7 cases (25%) and steatofibrosis in the other 14 cases (50%). The triggering factors were the abuse of alcohol in 27 cases and a pneumonia in the last case. The disease was characterized by fever, encephalopathy, hepatomegaly, hepatocytolytic-cholestatic syndrome. The evolution was dictated by the gravity of the background hepatic lesional substrate. PMID- 2575275 TI - [5-Fluorouracil (ftorafur) in the treatment of acute pancreatitis. Indications for and efficacy of its use]. AB - The main aim of the complex medical treatment in acute pancreatitis is the inhibition of exocrine pancreas secretion and decrease or annulment of the proteolytic effect, of autolysis, of its enzymes, both on the gland itself and on the neighbouring tissues. The authors introduced cytostatics of the 5 fluorouracil type (ftorafur) in the medical and/or medico-surgical treatment of 30 cases of acute pancreatitis admitted to the "Caritas" Surgical Clinic, during 1986-1987. The drugs lead to DNA-RNA inhibition and reduce significantly the pancreatic exocrine activity. Efficiency of 5-fluorouracil within the other therapeutic methods is proved by the results obtained, especially by the favourable rapid clinical evolution, blood amylase normalization in 48-72 hours, arrest in evolution of the pancreatic lesions. The treatment is economical and has no side effects. It may be also used for the digestive fistulae with pancreatic content or for the pure pancreatic fistulae. PMID- 2575276 TI - [Control of the metabolic state of diabetic patients by determining the concentration of serum glycosylated proteins (the fructosamine test)]. AB - The method for determining glycosylate serum proteins is based on the ketoamines property (fructosamine) of reducing nitro-tetrazoline blue, in alkaline medium, to a coloured, photometric product. The technique is simple, rapid, reproducible and cheap. The method was used for investigation of 52 diabetics and 17 normal subjects. The normal values were between 1.50-2.70 mmol/l, uncertain between 2.70 3.00 mmol/l, and certainly pathological above 3.00 mmol/l. The level of serum fructosamines shows the glycemia variations for an average period of about two weeks, before determination. It is one of the valuable parameters for detecting and following the patients with diabetes mellitus, and has also a prognostic value in the evolution of the disease. PMID- 2575277 TI - [Electrocardiographic and arterial pressure changes in the acute phase of subarachnoid hemorrhage]. AB - A prospective study was made of 30 patients, admitted to the neurology ward with subarachnoidal hemorrhage (SAH), at its onset. The diagnosis was established on the basis of anamnesis, clinical examination, spinal puncture, anatomopathological examination. The patients with other cerebrovascular affections or with antecedents of ischaemic cardiac affections were excluded. ECG tracings, serum ionogram, AT and VA at the onset and in evolution, and their modifications were followed and assessed in all the patients. The conclusion is reached that SAH in acute phase is associated with transitory ECG and pressure anomalies which become elements of unfavourable prognosis when persistent and deeply altered. They are valuable, at hand, elements in the differential diagnosis, and in the opportune therapeutical intervention. PMID- 2575278 TI - [Hereditary angioedema due to C1-esterase inhibitor deficiency]. AB - The paper presents a case of family oedema by shortage of C1-esterase inhibitor, characterized by appearance at an early age (8 months), participation in some attacks of nasal mucous membrane, with nasal obstruction and sinusal manifestations and also the abnormally long period, up to 9 days, of some localized oedemas. The crises were absent during pregnancy. The study of four generations of the family showed the predominantly hereditary character of the genetic transmission. Two cases in which the disease apparently "overleapt" a generation, as clinical manifestations, were presented. PMID- 2575279 TI - [IgA deficiency in certain pathological states]. PMID- 2575280 TI - [The surgeon facing polyendocrinopathies: clinical approach. 1. Type 1 familial polyendocrinopathy]. PMID- 2575281 TI - [The surgeon facing familial polyendocrinopathies: clinical approach. 2. Type 2 familial polyendocrinopathy]. PMID- 2575283 TI - Particular neurological aspects in vascular autoimmune diseases. II. Cryoglobulinemic vasculitis and polyarteritis nodosa. AB - In this second part we present our clinical neurological observations in the other 8 cases: 5 presenting systemic vasculitis of cryoglobulinemic etiology, and 3 with polyarteritis nodosa with central and peripheral neurological manifestations. PMID- 2575282 TI - Polyclonal B-cell activation by bacteria that induce nonsuppurative sequelae. AB - The polyclonal B cell activation (PBA) process induced by Klebsiella pneumoniae K34 (klebs) and Yersinia enterocolitica 03 (yers) was investigated. Both heat inactivated bacteria and their cell wall biostructures (klebsM, muriene, protein I etc.) stimulate human blood B cells to differentiate into immunoglobulin secreting cells without prior proliferation and without T cells. Klebs-activated B cells secrete mainly IgM and to a lesser degree IgG (mainly IgG2). The PBA process was regulated by CD4+ cells and monocytes, but not by CD8+ cells. While interleukin 2 is able both to induce proliferation and to enhance differentiation in klebs-activated B cell cultures, the low-molecular-weight B cell growth factor (BCGF) did not lead to a significant amount of 3H-thymidine uptake. In addition, in klebs-activated B cell cultures various anti-polynucleotide autoantibodies and the 16/6 idiotype were detectable. Thus, bacteria that induce nonsuppurative sequelae (e.g. klebs, yers) can use several mechanisms to overcome tolerance in their host. PMID- 2575284 TI - Health-based reference values of the Mini-Finland Health Survey: 1. Serum gamma glutamyltransferase, aspartate aminotransferase and alkaline phosphatase. AB - The reference values for gamma-glutamyltransferase (GT), aspartate aminotransferase (ASAT) and alkaline phosphatase (AFOS) activities in serum have been produced on the basis of measurements done in the Mini-Finland Health Survey. A representative sample of all Finns aged 30 years or over comprised 8000 persons, of whom 99.2% participated in the actual health survey. Every effort was made to obtain reference values for the healthy ambulatory population. Three separate health-derived selection criteria were used to obtain such reference values for the above-mentioned enzymes: those based on the available literature, with minor modifications, the recommendations published by the Committee on Reference Values of the Scandinavian Society for Clinical Chemistry and Clinical Physiology, criteria that were obtained after subgroup comparisons of the obtained data, where all the factors affecting the enzyme levels were identified. The recommendations of the Expert Panel on Theory of Reference Values (1987) were strictly adhered to in the statistical analyses. The distribution of the serum activity of GT was very skewed. The overall intervals for men and women were 5.1 1460 and 4.7-748 U/l, respectively. The frequency distributions could be transformed to the normal ones logarithmically. The 95% inner reference intervals for GT in the three groups were 7-76, 7-65, and 8-57 U/l for men and 6-35, 6-30 and 6-32 U/l for women, respectively. For ASAT the full intervals of the enzyme levels in serum were 2.6-770 U/l for men and 8.3-172 U/l for women. After logarithmic transformation the respective reference intervals in the three selection groups were 14-42, 14-40 and 13-39 U/l for men and 13-33, 12-31 and 13 33 U/l for women. The full intervals of AFOS were 47.5-2755 and 5.4-816 U/l for men and women, respectively; after the logarithmic transformation the reference intervals of the three selection groups were 98-267, 97-254 and 97-264 U/l for men and 77-265, 75-231 and 75-250 U/l for women, respectively. PMID- 2575285 TI - Comparative susceptibility of five strains of Mansonia uniformis (Diptera:Culicidae) in Malaysia to infection with subperiodic Brugia malayi. AB - Five strains of Ma. uniformis from Malaysia were tested for their susceptibility to infection with subperiodic B. malayi. All were found to be susceptible with infection rates ranging from 62% to 100%. The susceptibility rates were directly related to the microfilarial densities of the cat at the time of feeding. Statistical analysis showed no significant difference (p greater than 0.05) among the means of the indices of experimental infection as well as the percentage of infective mosquitoes of the five strains and an old laboratory colony. They were all equally susceptible to subperiodic B. malayi. PMID- 2575286 TI - Acute effects of alprazolam and adinazolam on the concentrations of corticotropin releasing factor in the rat brain. AB - Corticotropin-releasing factor (CRF) is the major physiological regulator of the hypothalamic-pituitary-adrenal (HPA) axis. However, considerable evidence indicates that CRF may be responsible for integrating not only the endocrine, but the autonomic and behavioral responses of an organism to stress as well. In addition, clinical studies indicate that CRF of both hypothalamic and extrahypothalamic origin may be hypersecreted in major depression as well as other psychiatric disorders. These findings, taken together, led to the hypothesis that the efficacy of antidepressant and/or anxiolytic drugs may be related to their actions on CRF-containing neural pathways in the central nervous system (CNS). Therefore, alterations of CRF concentrations in 18 rat brain regions were studied after acute administration of a tricyclic antidepressant (imipramine) or one of two triazolobenzodiazepines (alprazolam or adinazolam) that possess anxiolytic properties typical of benzodiazepines, as well as purported antidepressant activity unique to these compounds. Treatment with alprazolam or adinazolam increased hypothalamic CRF concentrations, which was associated with lower plasma ACTH concentrations. In contrast, the concentration of CRF was markedly reduced in the locus coeruleus, amygdala, and several cortical regions by either triazalobenzodiazepine. Acute treatment with imipramine was without effect on CRF concentrations in any brain region studied. Of particular interest is the finding that the two triazolobenzodiazepines exert effects on CRF concentrations in the locus coeruleus and hypothalamus that are opposite to CRF changes seen after stress. PMID- 2575287 TI - Concentrations of mRNAs encoding for preprosomatostatin and preprocholecystokinin are increased after kainic acid-induced seizures. AB - Concentrations of preprosomatostatin-mRNA and preprocholecystokinin-mRNA were determined by Northern blot analysis in rats 2, 10, and 30 days after strong seizures induced by a single intraperitoneal injection of kainic acid. At all time intervals examined, levels of preprosomatostatin-mRNA were increased in the frontal cortex; so were levels of preprocholecystokinin-mRNA in the striatum. Transient increases, i.e., 2 days after kainic acid, of preprocholecystokinin mRNA were observed in the frontal cortex and the substantia nigra. Preprocholecystokinin-mRNA was reduced in the hippocampus 2 and 10 days after kainic acid. Both preprosomatostatin- and preprocholecystokinin-mRNA levels showed a tendency to be reduced in the amygdala/pyriform cortex at all three time intervals. The increases in mRNA levels suggest enhanced rates of synthesis of the respective neuropeptides subsequent to kainic acid-induced seizures. They may also reflect a prolonged increase in the activity of the respective peptide containing neurons. This is of special interest in the frontal cortex, since in this area both neuropeptides are found in interneurons and are widely colocalized with gamma-aminobutyric acid. PMID- 2575288 TI - Absence of DNA damage-mediated induction of human methyltransferase specific for precarcinogenic O6-methylguanine. AB - The ability of cultured normal human fetal liver and kidney epithelial cells to repair the premutagenic and precarcinogenic O6-methylguanine (O6-MeGua) DNA adduct was determined by directly monitoring its loss in cellular DNA and quantitating the number of O6-MeGua-DNA-methyltransferase (O6-MT) molecules per cell. Following treatment of the epithelial cells with the direct acting carcinogen N-methyl-N-nitrosourea (MNU), the loss of the O6-MeGua adduct was biphasic, exhibiting a half-life of 2.0 and 1.5 h in the liver and kidney cells, respectively. The activity of O6-MT in the liver and kidney epithelial cells in culture was 0.19 pmol/mg protein or 18,500 molecules/cell. The activity of O6-MT was maintained throughout the life of the cultures, i.e., 20 subpassages or 50 cumulative population doublings for the liver and kidney. In order to ascertain whether human fetal epithelial cells exhibit an induction of O6-MT, the cell cultures were treated with single and multiple conditioning doses of N-methyl-N nitro-N-nitroso-guanidine (MNNG) or gamma-irradiated and assayed for the amount of O6-MT. A 1 h exposure of cells to 2, 4, and 8 microM MNNG resulted in an 80 100% decrease of the initial O6-MT activity which was restored to the constitutive levels within 48 and 72 h post-treatment. Rat hepatoma cells, used as a positive control, increased their levels of O6-MT to 2.8-fold the constitutive levels following treatment with MNNG. Treatment of the human liver and kidney epithelial cells with chronic low doses of MNNG exhibited O6-MT levels identical to untreated cells. The O6-MT activity in epithelial cells remained unaffected upon pre-irradiation with 1.2 or 2.5 Gy of gamma-irradiation. PMID- 2575289 TI - Biochemical studies of promoters of carcinogenesis in rat liver. AB - Adult female rats were orally dosed with 1/5 to 3/5 the published LD50 of either promoters or putative promoters of carcinogenesis [hexachlorobenzene (HCB), alpha hexachlorocyclohexane (alpha-HCH), kepone and toxaphene] or noncarcinogens [coumaphos, EDTA, caprolactam, 8-hydroxyquinoline, titanium (IV) oxide, sodium diethyldithiocarbamate (DEDTC), and sucrose] at 21 and 4 h before sacrifice. The promoters selected in this study were all of the halogenated hydrocarbon class. At doses of 1/5 to 3/5 the LD50, all four promoters or putative promoters induced rat hepatic ODC activity. The seven noncarcinogens produced several biochemical effects at doses of 1/5 the LD50: increased serum alanine aminotransferase activity (SGPT) (caprolactam and DEDTC), decreased hepatic cytochrome P-450 content (DEDTC), and increased hepatic ODC activity (8-hydroxyquinoline and DEDTC). None of the seven noncarcinogens caused hepatic DNA damage or coordinate induction of hepatic ODC and cytochrome P-450. The results support the interpretation that several of these biochemical parameters are useful in distinguishing potential tumor promoters and noncarcinogens. PMID- 2575290 TI - Cytotoxicity and effect on mutagenicity of buffers in a microsuspension assay. AB - We have examined the effects of three buffers--Vogel-Bonner minimal E (VBM) and 0.15 and 0.015 M sodium phosphate, pH 7.4--and two concentrations of overnight cells (5x and 10x) on the mutagenicity of two pure compounds and two complex mixtures in strain TA98 using a modification of a microsuspension assay developed by Kado et al. (Mutation Research 121:25-32, 1983). The assay was performed by adding 50 microliters of cell concentrate of an overnight culture of TA98 resuspended in the appropriate buffer; 50 microliters of the same buffer or S9 mix; and 2 microliters of mutagen or dimethyl sulfoxide to a 1-dram vial or 13 x 150-mm test tube. The suspension was incubated for 90 min at 37 degrees C, top agar was added, and the contents poured onto a bottom agar of minimal medium. Cell concentration (5x vs. 10x) had little effect on the mutagenic potencies of the agents tested. The mutagenic potencies of the direct-acting agents (1 nitropyrene and diesel exhaust) were consistently lower with 0.15 M buffer compared to the mutagenic potencies of these agents with the other two buffers. The three buffers gave similar results for the indirect-acting agents (2 aminoanthracene and environmental tobacco smoke). The 0.15 M buffer was considerably cytotoxic in the absence of S9, which may explain why the direct acting agents were less potent with this buffer compared to the other buffers. VBM was also somewhat cytotoxic, but this did not appear to affect the mutagenic potencies of the agents studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575291 TI - Genotoxic effects of fly ash in bacteria, mammalian cells and animals. AB - The increasing use of fossil fuels has raised concerns about possible deleterious health effects of the final combustion product, fly ash. Seven ash samples from coal sources obtained from Battelle Columbus Laboratories were evaluated in the Salmonella/mammalian microsome mutagenicity assay to determine their mutagenic potential. While dimethyl sulfoxide extracts of five samples showed no mutagenicity, sample 102 caused an increase in the number of revertants per plate over controls in TA100 and TA98 with activation by liver homogenate (2-fold and 2.4-fold, respectively), and without (2-fold and 6-fold). This ash was thus evaluated in whole animal studies. Animals treated by inhalation or oral gavage were assayed for the presence of mutagens in the urine, micronuclei in polychromatic erythrocytes, and chromosomal aberrations in metaphase bone marrow cells. Those animals treated by inhalation were also examined for local damage in the lung. The assay for mutagens in the urine was negative as shown by the Ames assay with TA100 and TA98 and there was no increase in micronuclei or in metaphase aberrations. Histological sections from the animals treated by inhalation did not show the presence of particles, macrophage infiltrations and generalized lung damage. We tested the same fly ash with an in vitro cell transformation assay with the cell line Balb/c 3T3 subclone A31-1-13. Although there was not an increase in Type III foci, there was a dose-dependent increase of Type II foci in the treated cells over the controls. In one assay, there was approximately a 14-fold increase in Type II foci in the highest dose (2 mg/ml) compared to the solvent control. One other ash sample induced cell transformation without being markedly cytotoxic, while a third sample was highly toxic but did not induce transformation. PMID- 2575292 TI - Teratogenicity and toxicity of ethylene glycol monomethyl ether (2 methoxyethanol) in Drosophila melanogaster: involvement of alcohol dehydrogenase activity. AB - Ethylene glycol monomethyl ether (EGME) or 2-methoxyethanol (2-ME) is a toxic compound that has teratogenic effects in developing organisms similar to its oxidation product methoxyacetic acid (MAA). Alcohol dehydrogenase (ADH) is supposed to be involved with the oxidation of EGME into MAA. It has been shown here that Drosophila ADH dehydrogenates EGME in an in vitro test system. Three strains of Drosophila melanogaster, genetically different from each other with regard to ADH activities (qualitatively and quantitatively), were used to test the in vivo involvement of ADH with the oxidation of EGME into MAA. The toxicity of EGME in egg-to-adult and third instar larval-to-adult development is concentration and strain dependent. Higher detoxification occurs in the strain with increased ADH activity. EGME is much more toxic than its oxidation product MAA at the level of adult eclosion. Teratogenic effects were observed in the ADH negative strain in spite of lacking ADH activity. EGME is apparently a teratogenic compound by itself. PMID- 2575293 TI - Hantavirus infections in humans and commensal rodents in Singapore. AB - To determine the extent of hantavirus infection in Singapore, serological studies using the indirect immunofluorescent antibody (IFA) test were conducted on commensal rodents and on human patients in 4 diagnostic groups. Virus isolation using a Vero E6 cell line was performed on hantaviral antigen-positive rodent lung tissue. Of 142 rodents and 3 insectivores studied, 37 (26%) were seropositive for IFA. Rattus norvegicus was the predominant species captured, with the highest species-specific seropositive rate of 32% (36 of 113). A hantavirus strain, R36, was isolated from one R. norvegicus. Seropositive rates for human patients were: 8% respectively for dengue haemorrhagic fever suspects and for non-A non-B hepatitis patients, 3% for leptospirosis suspects and 2% for acute nephritis patients. 2 patients had marked liver dysfunction but mild renal involvement. This hepatitis-like manifestation appears to be a clinical variant of hantavirus infection. PMID- 2575295 TI - Happy union generates order? PMID- 2575296 TI - Huge undertaking--goal: ourselves. PMID- 2575294 TI - Serological survey of Hantavirus infection in French Polynesia. PMID- 2575297 TI - Effect of an inhibitor of noradrenaline uptake, desipramine, on cell proliferation in the intestinal crypt epithelium. AB - The intestinal mucosa receives an adrenergic innervation for which there is no commonly accepted function. However, in recent years, cell kinetic studies have raised the possibility that this innervation may be an important regulator of crypt cell proliferation. The effects of noradrenaline released from adrenergic nerves is terminated principally by re-uptake of the amine into the nerve and this process can be inhibited by the antidepressant drug, desipramine. In this report desipramine is shown to accelerate crypt cell proliferation in intact, but not in chemically sympathectomized rats, thus adding support to the notion that regulation of crypt cell division is an important function of the sympathetic nervous system. PMID- 2575298 TI - Mast cells in ulcerative colitis. Quantitative and ultrastructural studies. AB - The changes in the number and ultrastructure of mast cells were studied in 37 colonoscopical biopsies from patients with ulcerative colitis. Changes in the active stage of the disease and during remission were compared. Cell counts were performed on semithin sections stained with Giemsa after osmium tetroxide fixation. This method overcome the uncertain staining found after formalin fixation. Accumulation of mast cells accompanied by intense degranulation was found to be significant in the active stage of the disease. Two forms of degranulation were observed: discharge of the individual granules and protrusion and detachment of the cytoplasmic processes containing granules. The latter was a sign of rapid degranulation, as described earlier in animal experiments. Mast cells were closely associated with capillary blood vessels, Schwann cells, neural fibres, myofibroblasts and collagenous fibres, and were also present between epithelial cells. It is assumed that close topographic contact may also imply a functional correlation. PMID- 2575299 TI - Electron microscopic immunocytochemistry of prolactin secreting cells (PRL-cells) and growth hormone secreting cells (GH-cells) in the anterior pituitary gland of partially hepatectomized rats. AB - After 60% hepatectomy in rats, prolactin secreting cells (PRL-cells) and growth hormone secreting cells (GH-cells) of the anterior pituitary gland were distinctly identified by the protein A-gold procedure combined with electron microscopy. The animals were sacrificed by the decapitation at midnight at intervals of about 28, 76 and 124 h after the operation. The principal changes can be summarized as follows; (1) Hypertrophy of the Golgi complex, (2) Dilation of the rough endoplasmic reticulum (RER), (3) Increased numbers of secretory granules (markedly in GH-cells), and occurrence of granule extrusion or exocytosis, (4) Increased numbers of lysosomes, which were mostly seen at 124 h after the operation. These ultrastructural changes were remarkably observed in both PRL and GH-cells. Especially, the noticeable changes in PRL-cells after partial hepatectomy in the rat were new findings in this study. The above results suggest that hepatectomy induced synthesis and release of GH and PRL in cells from pars distalis. PMID- 2575300 TI - Membranocystic lesion in the brain in cerebrotendinous xanthomatosis. Histochemical and ultrastructural study with evidence of its ceroid nature. AB - A case is described of cerebrotendinous xanthomatosis with purely neurological manifestations. Cholestanol deposition in both affected and unaffected brain regions was markedly increased, reaching 18.5-20.8% of the sterol fraction. The unilateral lesions localized in the basal ganglia and cerebellar white matter featured perivascular accumulation of foam cells containing apolar lipid and ceroid. Necrosis with lipid-rich debris was a frequent finding often accompanied by prominent collagen deposition. Within these lesions there were numerous refractile thick membranes which, according to lipid histochemical techniques, could be qualified as ceroid-type lipopigment. It is suggested that the ceroid membranes arise extracellularly directly from the lipid-rich debris. Ultrastructurally, they were composed of convolutes of highly organized trilaminar membranes about 15 nm thick similar to those seen in intracellular ceroid granules. The membranes were embedded in an amorphous substance of low or medium density and were identical in their general appearance, stainability and fine structure to the membranocystic lesion in Nasu-Hakola disease and to the extracellular ceroid in atherosclerotic plaques. PMID- 2575301 TI - Quantitative morphological changes in endocrine pancreas of rats with spontaneous diabetes mellitus. AB - The present study describes the cytopathology of the pancreatic islets in 18-old male eSS rats with spontaneous diabetes mellitus as compared to aged-matched normal animals. Light-microscopic immunocytochemical and morphometric techniques were used to study islet-cell populations, while quantitative methods were employed specifically for the analysis of B-cell ultrastructure. The diabetic rats showed disruption of the islet structure and fibrosis in the stroma. The volume density (Vvi) of endocrine tissue and the Vvi and percentage of B cells were diminished, whereas the Vvi of exocrine tissue and the Vvi and percentage of D cells were increased. The number of medium and large islets as well as their mean volume (micron3) decreased in these animals. Pancreatic B cells from eSS rats showed an increase in the Vvi of endoplasmic reticulum, immature secretory granules and lysosomes. Conversely, the Vvi of total secretory granules and microtubules appeared diminished. The current observations contribute to our understanding of this useful animal model of diabetes mellitus, in the attempt to clarify the pathogenesis of the disease. PMID- 2575303 TI - Ultrastructural changes in rat liver sinusoids during storage in cold Euro Collins solution. AB - Changes in the sinusoids of rat livers stored in cold (2 degrees C) Euro-Collins solution for various periods were observed using combined scanning (SEM) and transmission electron microscopy (TEM). The sinusoidal endothelial cells were vulnerable to cold ischemia. Fenestrations of the endothelial cells were enlarged and became mesh-like after a 4-h preservation period. Following 8 h storage the sieve plates and cytoplasmic processes of the endothelial cells were destroyed and there was a tendency for the perikaryon to desquamate. Blebs derived from hepatocytes were seen after 4 h and these increased in number and size with prolonged preservation. Although the sinusoids were filled with blebs after 24 h preservation. no irreversible ultrastructural damage in the parenchymal cells was observed. Within 12 h storage, the liver had a mosaic pattern after perfusion fixation indicating uneven fixation and profound circulatory disturbance. These results suggest that endothelial cell destruction and/or numerous blebs may have unfavorable effects on the microcirculation of the transplanted liver after prolonged preservation. PMID- 2575302 TI - Establishment and characterization of an immature epithelial cell line (ENU-T-1) derived from a rat nephroblastoma. AB - A new cell line designated ENU-T-1 has been established from a xenotransplanted experimental rat nephroblastoma. The cultured cells are spindle-shaped or polygonal and are arranged in a wavy fashion morphologically similar to cultured embryonal renal epithelial cells. The cells exhibit a number of epithelial characteristics. Enzyme histochemistry gives positive reactions for gamma glutamyltranspeptidase and alkaline phosphatase, both of which are present in renal tubular epithelial cells. Immunofluorescence studies show positive reactions for vimentin and cytokeratin. When inoculated into athymic nude mice, the cultured cells form tumors composed of sheets of epithelial cells with focal tubular formation. This cell line may be of value in studying differentiation of nephroblastoma, and possibly normal nephrogenesis. PMID- 2575304 TI - [Activities of pain-treatment service in a polyclinic]. AB - The experience gained in the management of advanced cancer patients is discussed. Treatment including pharmaco- and psychotherapy was given in outpatient hospital and at home. Two more principles of cancer pain treatment, viz. combined application and early start, were suggested to add to those described in the literature: adequate dosage, stepwise use, regular uptake and preferred oral administration. In 79.8% of patients, complete or significant regression of pain did not require injections of narcotic drugs. Certain organizational changes aimed at improving cancer pain treatment are discussed. PMID- 2575305 TI - [The enzyme activity and thymol test of the blood serum in chronic alcoholics]. AB - The authors evaluated the enzymatic activity and thymol test of the blood serum in patients suffering of alcoholism. It was established that the spectra and degree of increase of the examined values in the blood serum differ in the first, second and third stages of the disease and, apparently, to a large extent are caused by functional or organic changes in the liver. PMID- 2575306 TI - [Reducing secretions in enteral nutrition]. PMID- 2575308 TI - Serotyping Bordetella pertussis strains. AB - The serotyping scheme for Bordetella pertussis, developed in the 1950s, depends on the presence or absence of various strains of three major agglutinogens, two of which have been shown to be fimbrial proteins, and several minor agglutinogens, the biochemical nature of which is unknown. This article reviews the reasons for the confusion which has recently arisen over the nomenclature of the serotype antigens and proposes a simplified serotyping scheme based on the fimbrial components. PMID- 2575307 TI - [Lung function during tocolysis with beta-stimulators and beta-1-blockers]. AB - The pulmonary function during pregnancy is foremost changed by the elevated diaphragm, which reduces the functional residual capacity. The lungs are less extended, so that the airway resistance increases. The application of a beta mimetic drug for tocolytic therapy could reduce the airway resistance. Because an additional selective beta-1-blocking drug for cardioprotection could interfere with this effect, the pulmonary function in pregnancy during tocolytic therapy was investigated by body plethysmography in 20 woman of the third trimester of gravidity. There were no apparent differences in the pulmonary function in these woman when an additional selective beta-1-receptor blockade was performed. The airway resistance even diminished during the beta blockade. This unexpected result is probably due to an stabilizing effect of the betablocker on the body fluid and the permeability of capillary membranes during tocolytic therapy. PMID- 2575309 TI - [Surveillance and assessment of undesirable effects in drug treatment: pilot project]. AB - Since 1986 the Institute for Health Systems Research Kiel has been constructing a system of intensive post marketing surveillance of new drugs by general practitioners. The purpose of the project is to develop a methodology for documenting the applications of new drugs and recording adverse drug reactions (ADR). The primary goal is to quantify adverse drug reactions and to discover previously unknown ADR. Participating physicians record their treatment of the patient and atypical events, which are then analysed for suspected ADR. This paper describes the documentation and evaluation methods and the current stage of research. The validity of the data collected on suspected ADR is evaluated by comparing the results obtained to those of other post marketing studies. PMID- 2575310 TI - Fatal intoxications in the age group 15-34 years in Denmark in 1984 and 1985. A forensic study with special reference to drug addicts. AB - This survey deals with the Danish part of a study on fatal intoxications conducted in the Nordic countries in 1984 and 1985 with special reference to drug addicts. There were 315 cases of fatal intoxications in people 15-34 years of age. These were examined at the Forensic Institutes in Denmark and described with reference to cause of death, sex, age and drug addiction. Of the deceased, 194 were drug addicts according to a specific definition of this term. Women accounted for 28% of all the fatalities investigated in the study and 24% of those in addicts. More than 90% of the deaths were caused by drugs, with ethanol as a contributory factor in approximately 40% of cases. Deaths caused by heroin/morphine predominated, causing 50% of the deaths among drug addicts, but legal drugs, such as dextropropoxyphene, methadone and ketobemidone were also frequent causes of death in this group. In half the cases the concentration of morphine in blood following injection of heroin/morphine was found to be equal to or less than 0.5 mumol/kg, and in only about one-tenth of cases was the blood concentration above 2.0 mumol/kg. PMID- 2575312 TI - [The immunology of the infection caused by the human immunodeficiency virus]. AB - In this work the data contained in the literature and obtained by the author are presented. These data may change the traditional concepts of the immunopathology of AIDS. The analysis of these data indicates that the explanation of disturbances in the immune system, attributing their cause to the cytocidal action of HIV, is simplified. HIV may infect cells containing no antigen CD4. Perhaps, the fusion of gp41 with the membrane of the target cells is necessary for the penetration of HIV into the cells. Macrophages serve as the main reservoir of HIV and may carry the virus to different organs. The prolonged latent period may be ascribed to cytotoxic lymphocytes specifically active against HIV and suppressing its replication. The progress of the disease is due to viral and cellular factors and depends on the functional changes in T-cells, B cells, macrophages, the formation of immune complexes, the presence of stimulating antibodies and autoimmune phenomena. PMID- 2575311 TI - [Analysis of T-cell subpopulations and expression patterns of lymphocytic activation markers in patients in the early phase following kidney transplantation using laser flow cytometry]. AB - In 10 patients after kidney transplantation the T cell subpopulations (CD4, CD8) and the number of activated lymphocytes (IL-2R and transferrin receptor+, 4F2+, HLA-DR+, CD3+) in the peripheral blood were determined. In 9 out of 9 cases with rejection a clear immune activation could observed. In patients with CMV associated rejection crisis the CD4/CD8 ratio was significantly higher compared with patients with rejection crisis but without CMV infection. In all patients with CMV infection (n = 5) an increase of activated lymphocytes was observed. In a clinical-immunological monitoring the dynamics of the CD4/CD8 ratio, the expression of activation marker (especially CD3+, HLA-DR+ and 4F2+) and the absolute number of lymphocyte subpopulations should included. PMID- 2575314 TI - Study on the origin of major histocompatibility complex (MHC) genes in recombinant mouse strains by detection of polymorphic variants of MHC class III gene, complement C4. AB - In recombinant mouse strains the elements of the major histocompatibility complex gene cluster are composed of those of the parental strains. The origin of elements except the S region was previously determined by immunological and biochemical typing methods. For determination of the origin of the S region and the possible location of the recombination event around the S region, Southern blot analysis was performed. By the detection of genetic polymorphic patterns of complement C4 gene in 2 of the 5 recombinant strains the recombination was localized down-stream of the C4 gene and before the D gene region. PMID- 2575313 TI - [The clinico-laboratory characteristics of cases of diseases connected with viruses of the California encephalitis complex in the inhabitants of Moscow]. AB - To study the role of viruses of the California encephalitis virus complex (the family Bunyaviridae) in infectious pathology, 187 fever patients admitted to the Clinical Infectious Hospital in May-September 1986 were examined. In 10 of these patients the neutralization test revealed the presence of diagnostically significant changes in neutralizing antibodies (neutralization indices), which was indicative of the role played by Tahyna virus or other related viruses belonging to the California encephalitis virus complex in the etiology of the diseases. The analysis of the clinical picture showed that in all patients the disease took an acute course in its initial stage, starting with shivering and characterized by high fever, headache, pronounced toxicosis, the possibility of the formation of intracerebral hypertension and pneumonia. PMID- 2575315 TI - Effect of N-ethylmaleimide treatment on naloxone binding in frog brain membranes. AB - Specific binding of (3H) naloxone to opioid receptors in frog (Rana esculenta) brain membranes was irreversibly inactivated by the sulfhydryl group alkylating agent N-ethylmaleimide (NEM). Saturation analysis of (3H) naloxone binding revealed a marked reduction in the number of ligand binding sites after N ethylmaleimide treatment. Pretreatment of the membranes with unlabelled opioid ligands, i.e. naloxone, morphine, or the kappa selective dynorphin (1-13), and sodium ions resulted in considerable protection of (3H) naloxone binding against the N-ethylmaleimide blockade. PMID- 2575316 TI - Vulvar transepidermal water loss (TEWL) decay curves. Effect of occlusion, delipidation, and age. AB - The kinetics of water desorption after water loading was evaluated by means of transepidermal water loss (TEWL) decay curves. The effects of delipidation and ageing on the desorption of the water biomolecule was investigated in the vulva and on the forearm. All decay constants were analysed by curve stripping analysis and found to fit a bi-exponential decay. There was no significant difference in decay constant when compared by site. However, the terminal decay constant differed significantly after delipidation in both vulva and on forearm (p less than 0.02, p less than 0.04, respectively) in premenopausal women. Significant differences were also noted at post-menopausal forearm and vulva sites after delipidation for the terminal decay constant (p less than 0.006, p less than 0.02, respectively). Delipidation probably alters bound water in the process of sorption. Differences in decay constant when compared between pre- and post menopausal women were noted only at the vulva for beta 1 decay constant (p less than 0.05). beta 2 of the forearm was not affected by menopause. Data are also presented to support the notion that structural lipids of the stratum corneum may have a water-holding property. PMID- 2575317 TI - 13-cis retinoic acid and dexamethasone modulate the gene expression of epidermal growth factor receptor and fibroblast proteoglycan 40 core protein in human skin fibroblasts. AB - The effects of 13-cis retinoic acid (RA) and dexamethasone on the levels of epidermal growth factor (EGF) receptor and fibroblast derived proteoglycan core protein (PG40) mRNAs were studied in human skin fibroblasts. The EGF receptor is involved in the regulation of cellular proliferation and the synthesis of matrix proteins, and proteoglycan 40 is important for cell attachment and interaction with collagen and fibronectin. 13-cis-RA at a concentration of 10(-7) M markedly reduced the levels of the EGF receptor and PG40 mRNAs, the decreases being 33 and 56%, respectively. Dexamethasone reduced these mRNAs markedly less. Simultaneous treatment of the fibroblasts with 13-cis-RA and dexamethasone resulted in similar decreases in EGF receptor and PG40 mRNAs as with 13-cis-RA alone. Surprisingly, the proliferation rate of the fibroblasts was increased in the presence of dexamethasone under conditions similar to those which caused slight decrease in the EGF receptor mRNA levels. This indicates that glucocorticoids also affect the cellular growth by mechanisms which do not involve EGF receptors. PMID- 2575318 TI - Immunochemical analysis of the distribution of the desmosomal protein desmoglein I in different layers of plantar epidermis. AB - An antiserum raised against the bovine desmosomal protein desmoglein I (DGI), Mr approximately 160 kDa, was used in an immunochemical analysis of human plantar epidermis. Different layers of the tissue were prepared by means of horizontal freeze sectioning. Loosely attached surface layers were obtained by means of scraping of the skin surface with a scalpel. Tissue extracts were analysed by means of sodium dodecylsulphate polyacrylamide gel electrophoresis followed by immunoblotting. Significant amounts of a component with Mr approximately 160 kDa, reactive with the DG I-antiserum, were found in all layers except the loosely attached surface layers. In these layers the antiserum detected a component with Mr approximately 80 kDa, not found in other layers. This component may be a degradation product of DG I. Since DG I belongs to the group of transmembrane desmosomal proteins that is believed to constitute the link between the intracellular parts of desmosomes of opposing cells, it is concluded that desmosomes may play an important role in plantar stratum corneum cell cohesion, and that degradation of desmosomes may be an important step in desquamation in plantar epidermis. PMID- 2575319 TI - Effect of simulated sunlight on Langerhans' cells in malignant melanoma patients. AB - The effect of artificial sunlight on the number and HLA class II expression of Langerhans' cells was studied in 10 patients with malignant melanoma and 10 control volunteers. The total number of Langerhans' cell decreased in both groups but at 96 h there was a greater and significant decrease (p less than 0.01) in the number of Langerhans' cells in the melanoma group, compared with controls. This decrease persisted and was still greater in the melanoma group (p less than 0.02) at one week post-irradiation. There was a rise in Langerhans' cell count over the following 3 weeks in both groups. Unexpectedly, during this period in the melanoma group-but not controls-there was a significant median peak rise above pre-irradiation levels (p less than 0.001). Alteration in the response of Langerhans' cells to sunlight may play a part in the aetiology of malignant melanoma. PMID- 2575320 TI - A prospective immunofluorescence study of immune deposits in the skin of primary Sjogren's syndrome. AB - There are conflicting opinions concerning the epidermal immunofluorescence pattern in primary Sjogren's syndrome. In a prospective study of 12 patients we found a characteristic pattern of epidermal nuclear/cytoplasmic IgG deposits in 8 (67%). This pattern was associated with the presence of antibodies against SSA/Ro and SSB/La in the serum and was also found in 2 out of 5 LE patients with monospecific antibodies against SSA/Ro. There is a resemblance to the pattern of dust-like particles described in the diseased skin of patients with subacute cutaneous LE. In one patient with primary Sjogren's syndrome, IgG deposits were confined to epidermal cell nuclei (in vivo ANA). Instead of antibodies against SSA/Ro or SSB/La, this particular patient had nRNP-antibodies. From this study, we conclude that the epidermal IgG deposits in primary Sjogren's syndrome may represent antibody binding to the sites within epidermal cells where the respective antigens are located. PMID- 2575321 TI - Detection of transferrin and C3d receptors in the skin of patients with various dermatoses. AB - The localization of transferrin and C3d receptors in various skin lesions and normal appearing skin have been studied on sections with the PAP technique. The transferrin receptor was recognized in the lower epidermis from psoriatic plaques. Here it was more evident than in other inflammatory or hyperproliferative disorders where it was mainly detected on the basal cells. In healthy skin or lesions of lichen planus, scleroderma and ichthyosis the transferrin receptor was not detected in the epidermis. The C3d receptor was in normal skin found on the basement membrane and on elastic fibres in the papillary dermis. The basement membrane was strongly marked in pemphigoid but was not seen in lichen planus and Ehlers-Danlos syndrome. In patients with urticaria factitia, contact dematitis, psoriasis and Darier's disease the suprabasal cells also expressed C3d whereas in other dermatoses the epidermis was negative. Colloid bodies in lichen planus and GVH reactions expressed both the transferrin receptor and C3d. PMID- 2575322 TI - Cytokine release from cultured peripheral blood mononuclear cells of patients with severe atopic dermatitis. AB - Peripheral blood mononuclear cells (PBMC) from 14 patients with severe atopic dermatitis (AD) and 11 healthy donors were tested for their capacity to produce tumour necrosis factor-alpha (TNF-alpha) after PHA stimulation and compared with their in vitro production of interferon-gamma (IFN-gamma). The mean TNF-alpha production in AD patients did not differ vis-a-vis controls. However, a significant portion of patients with AD which was defective in generating IFN gamma in vitro showed in addition significantly a decreased production of TNF alpha. No correlation could be found between TNF-alpha and neopterin production in either group, whereas there was a close overall correlation between the amount of TNF-alpha and IFN-gamma detectable in culture supernatants of patients and controls. Furthermore, a significant correlation was found between TNF-alpha and IFN-gamma generation in vitro and serum IgE concentration in AD. Based on cytokine production in vitro and IgE concentration in vivo, patients with severe AD could be divided into two groups. Furthermore, 3 AD patients with normal IFN gamma generation and low serum IgE concentration but suffering from eczema herpeticum formed a subgroup which showed an increased TNF-alpha production in vitro. The data suggest alterations in cytokine production in a subgroup of patients with AD which bear a reciprocal relationship to abnormal IgE regulation. PMID- 2575323 TI - Decreased retinyl ester concentrations in UV-induced murine squamous cell carcinomas. AB - Squamous cell carcinomas were induced in hairless mice by repeated irradiations with UVB (280-320 nm, total dose 30 J/cm2) plus UVA (320-400 nm, total dose 168 J/cm2). The irradiated animals and non-irradiated controls were fed on diets with or without vitamin A supplementation (20,000 IU/kg). At the appearance of tumours, 30 to 43 weeks after the last irradiation, the vitamin A (retinol plus retinyl ester) concentrations in the serum, liver, epidermis and tumours and the retinol esterifying activities in microsomes from epidermis and tumours were measured. The liver and epidermal vitamin A concentrations were 2-3 times higher in vitamin A supplemented than in unsupplemented animals, but did not differ between tumour-bearing animals and non-irradiated controls receiving identical diets. The vitamin A concentration in the tumours was significantly lower than in perilesional epidermis. The largest difference (p less than 0.001) between the tumour and epidermal values was observed in the vitamin A supplemented group. The low vitamin A content of the tumours was entirely due to a marked (2 to 6-fold) reduction in the retinyl ester fraction. In contrast, the retinol content of the tumours was increased to twice that of normal epidermis. The activity of the esterifying enzyme, acyl-CoA:retinol acyltransferase (EC 2.3.1.76), was unchanged. The reason for the reduced retinyl ester concentration thus remains unclear. Still, it is possible that a disturbed interconversion of retinol to retinyl esters plays a role in murine photo-carcinogenesis. PMID- 2575324 TI - Cryopreserved 3T3 fibroblasts retain their capacity to enhance the growth of human keratinocyte cultures. AB - Cultured epithelial grafting of full-thickness skin defects is a new promising possibility for the successful treatment of patients with large burns. The major obstacle to this method, however, is a 3-4-week interval between burn and grafting, which is necessary for the growth of sufficient quantities of cultured epithelium. Generally, growth-arrested murine 3T3 fibroblasts have been used with success as feeder layers to shorten the cultivation time of keratinocytes. In the present work we have initiated studies to determine whether or not cryopreserved growth-arrested 3T3 fibroblasts retain their capacity to enhance the growth of human keratinocytes in vitro. The results of this study show that the [3H]thymidine incorporation in cultures containing mitomycin C treated 3T3 feeder cells was significantly greater than in cultures without feeder cells. Furthermore, in keratinocyte cultures containing freshly separated or cryopreserved 3T3 fibroblasts, a similar rate of [3H]thymidine incorporation was observed and the activity of incorporation has never differed significantly during the 11 days of culturing, meaning that cryopreserved, growth-arrested 3T3 fibroblasts retain their ability to enhance the growth of human keratinocytes. This observation renders the continuous maintenance of 3T3 cells unnecessary in laboratories which want to culture keratinocytes without delay. PMID- 2575325 TI - Two binding sites for Ki67 related to quiescent and cycling cells in human epidermis. AB - The monoclonal antibody Ki67 (Ki67) binds to a nuclear antigen expressed by cycling cells of several human tissues and to the cytoplasm of the basal layer cells of squamous epithelia. We have used an immunohistochemical method to visualize the binding sites of Ki67 in normal and hyperproliferative epidermis. Cytoplasmic staining was present in the basal layer cells of normal epidermis, but was decreased in psoriatic and post-tapestripping epidermis. In sections of normal epidermis only a small minority of nuclei were positive, but sections of psoriatic epidermis and epidermis 40 and 48 h after tapestripping showed large numbers of positive nuclei in the basal and suprabasal layers. Since recent reports strongly suggest that the cell production rate is regulated by changes in the number of cycling cells, the hypothesis that Ki67 binds also in human epidermis to the nuclei of cycling cells is supported by the present findings. PMID- 2575326 TI - Use of sodium-chloride separated human skin in detection of circulating anti basement membrane zone antibodies. AB - The sensitivity of the indirect immunofluorescence (IIF) technique for detection of circulating basement membrane zone (BMZ) antibodies was evaluated, employing NaCl-separated human skin and intact skin as substrate. Consecutive serum samples from 12 patients with clinically, histologically and immunohistologically verified bullous pemphigoid (BP) were investigated in parallel on both substrates, in dilutions ranging from 1:10 to 1:1,280. All BP sera showed linear deposits of IgG at the BMZ on intact skin, with titres ranging from 10 to 160. On NaCl-separated skin, all BP sera produced a linear epidermal fluorescent band for IgG, with titres ranging from 80 to 1,280. None of the sera showed deposits of IgM anti-BMZ antibodies. Sera from 5 healthy donors (dilutions 1:10) produced no fluorescence, either on intact or on NaCl-separated skin. The serum-titres of circulating anti-BMZ IgG antibodies in 2 patients with corticosteroid-resistant BP were significantly reduced (from 160 to less than 10) during treatment with plasmapheresis, when using NaCl-separated skin as substrate for IIF, whereas the serum-titres showed insignificant reduction (from 20 to less than 10), when using intact skin as substrate. We conclude that the IIF method is more sensitive for detection of circulating anti-BMZ antibodies, when NaCl-separated skin as compared with intact human skin is employed as substrate. PMID- 2575327 TI - Clonidine-induced immune complex disease. AB - We report upon a 46-year-old woman, who developed immune complex disease after treatment with clonidine for one year. The diagnosis was verified with histological demonstration of IgG and IgM complexes as well as complement C1q, C3c and C4 between muscle fibres and at the dermo-epidermal junctions. The patient's symptoms abated and the abnormal results of blood tests reverted to normal following cessation of clonidine therapy. PMID- 2575328 TI - Stimulation of tyrosinase by dihydroxy phenyl derivatives. AB - Isoprenaline (0.3 mM) moderately increased the tyrosinase activity of cultured human melanoma cells, while another beta-adrenoceptor agonist, terbutaline (1-3 mM) and a catechol compound, dopac (0.1-0.3 mM) induced a several fold increase in the enzyme activity. Isoprenaline (0.3-1 mM) and dopac (0.3-1 mM) also exerted pronounced toxic effects on the cells. The data suggest: 1) a possible role for beta-adrenoceptors in the regulation of human melanogenesis; 2) two different ways of action for isoprenaline in inducing tyrosinase elevation; 3) the possible usefulness of dopac as a chemotherapeutic agent. PMID- 2575329 TI - Acquired pigmented macules in human piebald lesions. Ultrastructure of melanocytes in hypomelanotic skin. AB - Two cases of piebaldism are reported. The first patient was a 9-month-old girl with inborn hypopigmented areas on the frontal region of the scalp and both knees. There were no melanocytes in the lesions. In the second case, we observed the patient from 2 months of age for a period of 9 years. Many hyperpigmented spots appeared on the hypomelanotic areas on the frontal region of the scalp, abdomen and both knees. Electron-microscopic examinations of the hypomelanotic skin disclosed an area with regularly distributed melanocytes as well as an area with no melanocytes. Most of the melanosomes were ellipsoidal and lamellar. They were in stage II to III, which signified delayed pigmentation. Hyperpigmented spots were slightly enlarged following PUVA treatment. PMID- 2575330 TI - Plasmin-like proteinase associated with high molecular weight complexes in blister fluid of bullous pemphigoid. AB - Blister fluid from tense bullae of 10 patients with bullous pemphigoid was investigated using a radial caseinolysis assay and zymography. Proteolytic activity, varying from 4.7 to 10 micrograms/ml, was found in 3 out of 10 patients, by using the caseinolysis assay. Zymography revealed that a major part of this caseinolytic activity co-migrated with plasmin standard. In addition, in the zymography, proteolytically active high molecular weight complexes were seen. This characteristic pattern was seen in the zymography of both positive and negative samples in the caseinolysis assay. These high molecular weight complexes were not seen in the zymography of the blister fluid of 2 patients with epidermolysis bullosa or in the suction blister fluid of 3 healthy control patients. These findings suggest that plasmin is generated at some phase of the blister formation, being possibly involved in the pathomechanism of bullous pemphigoid. PMID- 2575331 TI - Xeroderma pigmentosum: squamous cell carcinoma of the tongue. AB - A case report is presented of a 9-year-old boy with xeroderma pigmentosum complementation group C, who died from a squamous cell carcinoma arising from the tip of the tongue. Treatment with etretinate and in a later phase with indomethacin and prednisolone was not effective, except for a limited initial response of the tumour to etretinate. PMID- 2575332 TI - Familial sarcoidosis: high ethnic prevalence. AB - We report three sisters of Irish extraction who all developed sarcoidosis. The cases emphasize both the familial and ethnic preponderance of sarcoidosis which has not been adequately emphasized in the dermatology literature. PMID- 2575333 TI - Clinical findings in 61 patients with progressive systemic sclerosis. AB - In this report the case histories and working conditions of 61 patients with progressive systemic sclerosis (PSS) were evaluated and compared with those of age- and sex-matched controls. An extreme female predominance was found and the sclerodermal involvement of the trunk was also commonly demonstrated. Prior occupational exposure to chemicals (mainly organic solvents) was found in 28% of the patients. Furthermore a high proportion of menstrual bleeding disturbances was found. PMID- 2575334 TI - Retinoids plus PUVA (RePUVA) and PUVA in mycosis fungoides, plaque stage. A report from the Scandinavian Mycosis Fungoides Group. AB - Sixty-nine patients with mycosis fungoides, plaque stage, were treated in an open study with photochemotherapy (PUVA) or the combination of oral retinoids and PUVA (RePUVA). The response rate of Re-PUVA was equal to that of PUVA, with complete remission in 73% and 72%, respectively. Remissions were obtained with fewer PUVA sessions, and with a lower UVA dosage, if PUVA was combined with retinoids. A lower UVA dosage was needed if treatment was given four times weekly in stead of twice weekly. The duration of the remissions tended to be prolonged if retinoids were given as maintenance therapy. PMID- 2575335 TI - Low doses of zinc gluconate for inflammatory acne. AB - The effect of zinc on acne is unclear. In this study, only patients with an inflammatory acne were included in a double-blind trial using low doses of zinc gluconate (200 mg/day, corresponding to 30 mg zinc metal). We obtained a significantly different result between zinc and placebo groups in the inflammatory score (p less than 0.02). This efficiency could be explained by the action of zinc on inflammatory cells, especially granulocytes. PMID- 2575336 TI - Unilateral skin conditions after hemiparesis. PMID- 2575337 TI - The management of 138 psoriatic arthritic patients. AB - Clinical experience obtained in the management of 138 patients of psoriatic arthritis is reported. The correct recognition of arthritic subtype (according to Moll and Wright classification) always resulted essentially in the choice of the therapy. Our programme included rehabilitative, pharmacologic and surgical approaches. Our data suggest that psoriatic arthritis is a mild articular disease when compared to other affections such as rheumatoid arthritis or ankylosing spondylitis. Notwithstanding an accurate therapeutical programme, it is necessary to control atypical cases which not infrequently can occur. PMID- 2575338 TI - The role of catecholamines in estradiol and progesterone secretion by cultured explants and cells of human term placentae. AB - The effects of physiological concentrations of the native catecholamines norepinephrine and epinephrine upon term placental hormonal function were examined by measuring estradiol and progesterone secretion by organ and cell culture systems. Results show that, in explants, both catecholamines caused a significant increase in the secretion of both sex steroids, p less than 0.05. Estradiol secretion was blocked by the alpha and beta adrenergic receptors antagonists, phenoxybenzamine and propranolol, respectively, p less than 0.05. Norepinephrine but not epinephrine dependent progesterone secretion was blocked by propranolol. In cells, epinephrine stimulated cyclic AMP generation and caused a 30% increase in estradiol secretion, p less than 0.05. Both were abrogated by propranolol. Norepinephrine increased secretion by 25%, p less than 0.05. This was inhibited by yohimbin and prazosin, alpha-1 and -2 receptors antagonists, respectively. In conclusion, the placenta in vitro is a target organ for catecholamines. The marked response of the explant system as compared with the marginal response of the cell culture system indicates that cell to cell contact/communication is required for full expression of catecholamine effect. PMID- 2575339 TI - Effect of isoprenaline on the output of melatonin from fetal and newborn lamb pineal glands in vitro. AB - We have measured the output of melatonin in vitro from the pineal glands of lambs in late gestation (135-143 days) and the early newborn period (4-8 days). The basal output of melatonin/mg pineal tissue was significantly lower in the fetal group (16.3 +/- 3.9 pg melatonin.(30 min)-1.mg-1) than in the newborn group (148.1 +/- 43.6 pg melatonin.(30 min)-1.mg-1). Addition of the beta-adrenergic agonist, isoprenaline (10(-5) mol/l) significantly stimulated melatonin output from both the fetal (to 24.9 +/- 3.9 pg melatonin.(30 min)-1.mg-1) and newborn pineals (to 247.7 +/- 67.3 pg melatonin.(30 min)-1.mg-1). Pineals from newborn lambs produced 9-10-fold more melatonin than the fetal pineal glands, before, during and after addition of isoprenaline. These results show that functional beta-adrenergic receptors are present before birth on the sheep pinealocyte and that there is a marked increase in the melatonin synthetic capacity of the pineal in the newborn period. PMID- 2575340 TI - Transplacental effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on brain dopaminergic neurons in the mouse. An immunohistochemical study. AB - Immunohistochemical studies of monoamine neurons were performed to evaluate toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on young adult mice and compare them with those of their offspring. Mice, 9-11 weeks old (C57BL/6J), injected subcutaneously with a large dose of MPTP (17 mg/kg per day) during pregnancy on Day 9 and 12 of gestation (G9 and G12) miscarried and were examined at 13 weeks of age. Conversely, mice treated during pregnancy with sequential low dose of MPTP (2.8 mg/kg per day at G9-G17 for 8 days) successfully delivered their babies and were examined at the age of 15 weeks. Baby mice were examined at 1 and 6 weeks of age. The tyrosine hydroxylase-, aromatic L-amino acid decarboxylase- and dopamine (DA)-immunoreactive density of caudoputamen was reduced in 13-week-old mice treated with high dose of MPTP but not in the 15-week old mothers exposed to a low dose of MPTP as compared to their respective controls. The DA-immunoreactive density of the caudoputamen was the only staining that was reduced in both 1- and 6-week-old baby mice. In conclusion, these results demonstrate that MPTP injected to pregnant mice causes a DA depletion in the striatum of their offspring indicating a transplacental effect of MPTP. The findings also indicate that fetal brain is more susceptible to MPTP toxicity than the brain of young pregnant mice. PMID- 2575341 TI - Effect of combination of drugs with acupuncture on analgesic efficacy. AB - In rabbit experiments, some drugs used in clinics were selected and combined with electroacupuncture to observe the effect of drugs on acupuncture analgesia (AA). According to the effect of drugs on AA, the drugs were divided into three kinds: (1) Drugs with potentiating effect: fentanyl, pethidine, droperidol, perphenazine, metoclopramide, fenfluramine, tetrahydrocannabinol, fentanyl plus droperidol, fentanyl plus fenfluramine. (2) Drugs with reducing effect: ketamine and diazepam, (3) Drugs with no effect: sulpiride. PMID- 2575342 TI - Electro-acupuncture modifies humoral immune response in the rat. AB - The immunomodulating properties of "Shangqiu" (LP-5), "Ququan" (H-8), and "Rangu" (R-2) points were studied in several experiments performed on male Wister rats treated bilaterally by acupuncture (A) or electro-acupuncture (EA). On the stimulation day 3, the sheep-red-blood cells (SRBC) antigen was injected intraperitoneally and four days later, the immunological tests (plaque forming cells-PFC, direct microhemagglutination) were performed. Also, the relative weights of lymphoid organs (spleen and thymus) and adrenal gland were derived after sacrifice. The results obtained suggest pronounced immunomodulating properties of 200 Hz cathodal current stimulation at H-8 point. The immunosuppression observed reflected in a decreased number of PFC and reduced relative weights of adrenal gland revealed in all A- or EA-treated groups. PMID- 2575343 TI - Acupuncture as therapy of traumatic affective disorders and of phantom limb pain syndrome. AB - Functional isomorphism holds between four essential properties of acupuncture and of meditation, namely, 1) alpha rhythm prominent in electro-encephalograms (EEG); 2) deep general relaxation; 3) high degree of unresponsiveness to ordinarily painful stimuli; 4) participation of virtually the entire body. It is postulated, subject to experimental test, that a "stillness" prevails during acupuncture similar to the quiet of meditation. The quiet of meditation and by postulate, the "stillness" of acupuncture, provide high degree of unresponsiveness to aversive components of conditioned stimuli which had habitually reactivated affective trauma. This marked unresponsiveness accounts for the "stillness" and its EEG alpha rhythm. With its low noise level the "stillness" also provides the cerebral cortex better resolved, more intense signals relative to background and more comprehensive, clear information. The cortex can then call upon newly mobilizable, more precise regulation for removing imbalances throughout the body. The same factors apply to the therapy by acupuncture of phantom limb pain syndrome if the pain impulses from the limb, while attached, is the unconditioned stimulus of a reflex in which impulses from inner organs function as conditioned stimuli. Successful therapy of the syndrome using laser-stimulated acupuncture points is discussed accordingly. Emphasized is the desirability to maximize the "stillness," possibly by monitoring the course of therapy by displayed EEG. PMID- 2575345 TI - An hypothesis for the prolonged effect of acupuncture. AB - A comparison of acupuncture treatment methods, schedules, and results with the training methods, and results of the experiments involved in the training of various autonomic functions, shows many similarities. Both require a number of treatments or training sessions, both utilize a reward, and both produce an effect that lasts for a length of time after the last treatment or training session. From this information, it would appear that it is possible that the mechanism for the prolonged effect of acupuncture in treating chronic pain is that the repeated activation of the physiological systems by which acupuncture inhibits pain, by the repeated acupuncture treatments, trains the body to continue this activity and thereby maintains the pain relief for a period of time after the last treatment. PMID- 2575344 TI - Change of Leu-enkephalin- and B-endorphin-like immunoreactivity in the hippocampus after electroconvulsive shock and electroacupuncture. AB - To determine whether the effect of electroacupuncture (EA) on electroconvulsive shock (ECS) was through affecting endogenous opioid peptidergic system in the hippocampus, we used radioimmunoassay (RIA) to measure leu-enkephalin- and beta endorphin-like immunoreactivity (L-E-LI and Beta-E-LI) in the hippocampal perfusate after ECS and EA treatments. Wistar rats were given ECS stimulation, which caused behavioral and electroencephalogram (EEG) convulsions. However, EA could suppress ECS-elicited convulsions (including both behavioral and EEG abnormalities). The results of RIA showed that after repeated ECS treatments, the contents of L-E-LI and Beta-E-LI increased significantly by 136% and 157%, respectively. In contrast, EA treatment depleted alterations of L-E-LI and Beta-E LI induced by ECS, depleting L-E-LI by 32% and Beta-E-LI by 85%. These observations suggest that anticonvulsive action of EA is related to the release of L-E and Beta-E in hippocampus, probably through decreasing their release, thus to exert EA action. PMID- 2575346 TI - Diagonal ear-lobe crease: possible significance as cardio-vascular risk factor and its relationship to ear-acupuncture. AB - The diagonal ear-lobe crease, detectable especially after the age of 40, is still accepted as a sign of coronary heart disease risk. In the literature some authors report an association between anxiety and coronary heart disease. In our work a group of 143 patients with ear-lobe crease showed - in both sexes and in all examined decades (5th, 6th, 7th) - higher levels of anxiety than in the control group. The possible significance of the crease has been considered on the grounds of present knowledge of ear-acupuncture and the somatotopic mapping of CNS on the ear-lobe. PMID- 2575347 TI - Connections found between each meridian (heart, stomach, triple burner, etc.) & organ representation area of corresponding internal organs in each side of the cerebral cortex; release of common neurotransmitters and hormones unique to each meridian and corresponding acupuncture point & internal organ after acupuncture, electrical stimulation, mechanical stimulation (including shiatsu), soft laser stimulation or QI Gong. AB - Using the "Bi-Digital O-Ring Test Imaging Technique", the author has been able to accurately localize meridians and acupuncture points that correspond to specific internal organs and has found that most general patterns of meridians and the number of acupuncture points on each of the meridians of specific internal organs of the 12 main internal organs described in the literature of ancient Chinese medicine, are more or less correct, with the exception of some variations and inaccuracies. Each meridian of specific internal organs was found to be connected to the organ representation area in the cerebral cortex of specific internal organs. The acupuncture point has an area and occupies 3-dimensional space. It has a circular or slightly oval boundary with diameter in the range of 3 mm to 2.7 cm, although 6-12 mm are the most common diameters in human adults, with the exception of the area outside the corners of the nailbeds of the fingers and toes. Using the "Bi-Digital O-Ring Test Molecular Identification Method", the author also found that within the boundary of most acupuncture points and meridian lines (including Heart, Stomach, and Triple Burner) were high concentrations of neurotransmitters and hormones, including Acetylcholine, Methionine-Enkephalin, Beta-Endorphin, ACTH, Secretin, Cholecystokinin, Norepinephrine, Serotonin, and GABA. On all these meridian lines, in addition to the above neurotransmitters and hormones, Dopamine, Dynorphin 1-13, Prostaglandin E1 (PGE1) and VIP were found, but the latter do not usually exist within the boundary of the acupuncture point with the exception of the center midline of the acupuncture point where the meridian line is situated. Serotonin, Norepinephrine, and Cholecystokinin appeared in either one of the above 2 patterns, depending on the individual. Usually, no significant amounts of these neurotransmitters and hormones were found at the surrounding area outside of meridian and acupuncture points. However, the essential amino acid L-Tryptophan (which is a precursor of Serotonin), was usually found outside of the boundary of the acupuncture point and the meridian but not within the boundary of the acupuncture point and the meridian. Wherever Serotonin appeared, L-Tryptophan disappeared significantly and when the Serotonin disappeared, L-Tryptophan reappeared. In addition to the above common neurotransmitters and hormones, the Heart meridian had additional Atrial Natriuretic Peptide in both the meridian and its acupuncture points. Similarly, the Stomach meridian had additional Gastrin in both the meridian and its acupuncture points. Likewise,the Triple Burner meridian had additional Testosterone (in the male) and Estrogen (especially Estriol and Estradiol in the female. PMID- 2575348 TI - Profound toxicity of deoxyadenosine and 2-chlorodeoxyadenosine toward human monocytes in vitro and in vivo. AB - Deoxyadenosine is known to be toxic to both proliferating and resting lymphocytes that lack adenosine deaminase (ADA) activity. We now show that human monocytes are also highly sensitive in vitro to nanomolar concentrations of deoxyadenosine plus the ADA inhibitor deoxycoformycin, and to the ADA-resistant analogue 2 chlorodeoxyadenosine (CdA). Monocytes exposed to deoxyadenosine or to CdA in vitro accumulate massive DNA damage detectable within 1 hour. The DNA damage in monocytes exposed to CdA is associated with a decrease in protein synthesis and with inhibitions of phagocytosis and IL-6 secretion. However, unlike lymphocytes with similar DNA damage, the monocytes show no significant NAD or ATP depletion until cell viability declines. The selective toxicity of CdA to monocytes was confirmed by in vivo studies. In almost all patients receiving CdA infusion chemotherapy for cutaneous lymphoma, the blood monocytes counts fell to near 0 during one week of therapy. Our results suggest that CdA and related compounds may have potential clinical use in the therapy of immune disorders associated with monocyte/macrophage activation. PMID- 2575349 TI - The mechanism of 2-chlorodeoxyadenosine-induced cell death. PMID- 2575350 TI - Recovery of the activities of IMP dehydrogenase and GMP synthase after treatment with tiazofurin and acivicin in hepatoma cells in vitro. PMID- 2575351 TI - Kinetic properties of IMP dehydrogenase purified from rat hepatoma 3924A. PMID- 2575353 TI - [Undescended testis cancer: report of two cases--review of the literature of 179 cases in Japan]. AB - Recently, we experienced two cases of testicular tumor in patients with cryptorchidism. Case 1: A 35-year-old man was admitted because of right inguinal mass. He had a tumor of right undescended testis and underwent right orchiectomy. Case 2: A 45-year-old man, who was pointed out to have bilateral cryptorchidism was admitted because of right groin mass. He underwent right orchiectomy and left orchiopexy. Histological examination of two cases were seminoma. Testicular tumor in undescended testis was made with 179 reported cases from the Japanese literature. PMID- 2575352 TI - Two distinct target sites on IMP dehydrogenase in chemotherapy. PMID- 2575354 TI - Enzymes of glutamine metabolism in inflammation associated with skeletal muscle hypertrophy. AB - Glutamine synthesis and utilization were studied in the plantaris muscle after removal of its functional synergists, the soleus and gastrocnemius muscles. Rat plantaris muscle was compared with unoperated controls at 7, 14, and 30 days after synergist ablation and induction of hypertrophy. Glutamine synthetase activity increased from 6.17 +/- 1.77 to 33.92 +/- 2.23 nmol.h-1.mg protein-1, and glutaminase activities increased from 98.63 +/- 23.05 to 478.70 +/- 64.17 nmol.h-1.mg protein-1 7 days after surgery and remained elevated at 14 and 30 days. Sham-operated controls examined 7 days after surgery did not exhibit significantly increased glutamine synthetase activity. Histological examination revealed a large proliferation of connective tissue cells, as well as cells involved in tissue repair and inflammation; this influx was maximal 1 wk after surgery. The activity of the oxidative enzymes of the pentose phosphate pathway increased from 3.08 +/- 4.31 to 20.86 +/- 1.13 nmol.min-1.mg protein-1 1 wk after surgery. The time course of changes in pentose phosphate pathway enzymes was similar to that of the increases in glutamine synthetase, glutaminase, and cellular infiltration. Increases in muscle wet weight followed a different time course than changes in glutamine synthetase, glutaminase, and pentose phosphate pathway activities. It is concluded that the initial increases in plantaris muscle weight are probably due to edema, connective tissue proliferation, and cells involved in tissue repair and inflammation. The increase in glutamine synthetase activity appears to occur in skeletal muscle, whereas the changes in glutaminase and pentose phosphate pathway activities appear to represent infiltrating inflammatory cells. Furthermore, the increase in glutamine synthetase activity may serve to support the infiltrating cells, which appear to lack substantial capacity for glutamine production. These results represent a functional relationship between skeletal muscle glutamine synthesis and utilization by cells mediating inflammation and connective tissue repair and synthesis. PMID- 2575355 TI - Role of the gamma-glutamyl cycle in the regulation of amino acid translocation. AB - Amino acid translocation was studied in the mammary gland of lactating rats and in the placenta of pregnant rats. The uptake of amino acids by the mammary gland is maximal on days 10-14 of lactation and is minimal on days 19-21. However, on day 19 maximal uptake can be restored by injection of 1) small amounts of gamma glutamyl amino acids, 2) 5-oxoproline, and 3) an inhibitor of 5-oxoprolinase. A severe decrease in uptake of amino acids at the peak of lactation is provoked by anthglutin, an inhibitor of gamma-glutamyltranspeptidase (GGT). Simultaneous injection of 5-oxoproline blocks these effects of anthglutin. In pregnant rats, inhibition (79%) of placental GGT activity by acivicin results in a 50% decrease of placental L-[U-14C]-alanine transfer and 70-80% decrease in its incorporation into the placental and fetal proteins. Infusion of 5-oxoproline to mothers previously treated with acivicin restored the L-[U-14C]-alanine transfer. Acivicin or 5-oxoproline did not modify the transfer and metabolism of D [U14C]glucose by the fetal placental unit. These results show that the gamma glutamyl cycle should not be considered a mechanism for amino acid transport but rather a generator of extracellular signals, gamma-glutamyl amino acids, that are converted intracellularly to 5-oxoproline, which activates uptake and/or metabolism of amino acids. PMID- 2575356 TI - Catecholamines relax portal and mesenteric veins from normal and portal hypertensive rats. AB - The relaxation by catecholamines of superior mesenteric veins and portal veins, precontracted by 65 mM KCl, was studied after a 2-h exposure to phenoxybenzamine. The veins were obtained from portal-hypertensive and sham-operated rats. The beta 2-selective antagonist ICI 118551 attenuated the relaxation caused by epinephrine and isoproterenol but did not change the relaxation caused by norepinephrine in superior mesenteric veins. The beta 1-specific antagonist CGP 20712A reduced the relaxation caused by norepinephrine but only marginally attenuated those caused by epinephrine and isoproterenol in superior mesenteric veins. The combination of ICI 118551 and CGP 20712A abolished the relaxation caused by the catecholamines in superior mesenteric veins. The relaxation caused by norepinephrine, epinephrine, and isoproterenol was markedly reduced by ICI 118551 in portal veins. The pattern of antagonism was similar in veins from portal-hypertensive and sham-operated rats. The results suggest that both beta 1- and beta 2 adrenoceptors mediate relaxation induced by catecholamines in superior mesenteric veins. Relaxation of portal veins appears to be mediated mostly by beta 2 adrenoceptors. PMID- 2575357 TI - Cellular and molecular mechanisms of chemical synaptic transmission. AB - During the last decade much progress has been made in understanding the cellular and molecular mechanisms by which nerve cells communicate with each other and nonneural (e.g., muscle) target tissue. This review is intended to provide the reader with an account of this work. We begin with an historical overview of research on cell-to-cell communication and then discuss recent developments that, in some instances, have led to dramatic changes in the concept of synaptic transmission. For instance, the finding that single neurons often contain multiple messengers (i.e., neurotransmitters) invalidated the long-held theory (i.e., Dale's Law) that individual neurons contain and release one and only one type of neurotransmitter. Moreover, the last decade witnessed the inclusion of an entire group of compounds, the neuropeptides, as messenger molecules. Enormous progress has also been made in elucidating postsynaptic receptor complexes and biochemical intermediaries involved in synaptic transmission. Here the development of recombinant DNA technology has made it possible to clone and determine the molecular structure for a number of receptors. This information has been used to gain insight into how these receptors function either as a ligand gated channel or as a G protein-linked ligand recognition molecule. Perhaps the most progress made during this era was in understanding the molecular linkage of G protein-linked receptors to intramembranous and cytoplasmic macromolecules involved in signal amplification and transduction. We conclude with a brief discussion of how synaptic transmission leads to immediate alterations in the electrical activity and, in some cases, to a change in phenotype by altering gene expression. These alterations in cellular behavior are believed to be mediated by phosphoproteins, the final biochemical product of signal transduction. PMID- 2575358 TI - Inhibitory effect of adenine nucleotides and anti-allergic drugs on phosphorylation of phosphatidylinositol in rat mast cell granules. AB - Rat mast cell granules were obtained by sonication of highly purified rat mast cells and isolated in a Percoll gradient. Phosphorylation of endogenous phosphatidylinositol in rat mast cell granules, which is catalyzed by phosphatidylinositol kinase in the granules, was assayed by measuring the incorporation of 32P from [gamma 32P]ATP into phosphatidylinositol 4-phosphate. Lipids were isolated with methanol/chloroform/HCl and were separated by thin layer chromatography on oxalic acid impregnated silica gel plates. Phosphatidylinositol 4-phosphate areas were identified by staining with iodine, scraped and measured for 32P radioactivity. The phosphorylation reaction was inhibited by 50-500 microM adenosine, ADP and 500 microM AMP in a concentration dependent manner. Among several anti-allergic drugs investigated. 100-1000 microM theophylline and 10-100 microM azelastine inhibited the phosphorylation reaction, but disodium cromoglycate and ketotifen had little effect. PMID- 2575359 TI - Derivatization of gamma-glutamyl semialdehyde residues in oxidized proteins by fluoresceinamine. AB - Oxidative modification of proteins is implicated in a number of physiologic and pathologic processes. Metal-catalyzed oxidative modification usually causes inactivation of enzymes and the appearance of carbonyl groups in amino acid side chains of the protein. We describe use of fluoresceinamine to label certain of those carbonyl groups. Fluoresceinamine reacted with those carbonyl groups to form a Schiff base which was reduced by cyanoborohydride to yield a stable chromophore on the oxidized residue. The high molar absorbtivity of the fluorescein moiety conferred high sensitivity upon the method. Labeled peptides were readily identified after tryptic digestion of oxidized glutamine synthetase. Further, acid hydrolysis of labeled glutamine synthetase allowed isolation of the derivatized, oxidized residue. The oxidized amino acid was identified as gamma glutamyl semialdehyde. During metal-catalyzed oxidation, the inactivation of glutamine synthetase paralleled the appearance of gamma-glutamyl semialdehyde. PMID- 2575360 TI - Restriction fragment length polymorphisms for growth hormone, prolactin, osteonectin, alpha crystallin, gamma crystallin, fibronectin and 21-steroid hydroxylase in cattle. AB - Genomic DNAs from animals representing six breeds of cattle (Angus, Brahman, Hereford, Holstein, Jersey and Texas Longhorn) were screened with cloned gene probes in a search for restriction fragment length polymorphisms (RFLPs). Eleven RFLPs were identified using seven different probes: growth hormone, prolactin, osteonectin, alpha A-crystallin, gamma crystallin, fibronectin and 21-steroid hydroxylase. The frequencies of the alleles identified by each probe were calculated and compared in a limited sampling of the six bovine breeds. These polymorphisms greatly enhance the pool of immunogenetic, biochemical and molecular markers available in cattle for linkage analysis, testing of parentage, and distinction of breeds. PMID- 2575361 TI - Mapping human disease-associated genes. PMID- 2575362 TI - [Bronchial manifestation of drug-induced complications]. AB - Bronchial side effects of drugs are varied and numerous. The most frequent are the hypersensitivity type 1 and 3 reactions of asthma. Asthma is primarily caused by anti-infectious agents but also by protein drugs (and many others). At the present time, attention is being focused on excipients and solvents: cremophore, anti-oxidative sulfites (E 220 to E 227), found in over 700 drugs and responsible for severe side effects. Other bronchospasms are due to direct or indirect potentiation of parasympathetic bronchomotor tonus, chiefly with alpha-agonists, and perhaps with beta-agonists but this remains to be proven. Asthmatic reactions caused by interference in mediator synthesis are another current topic of study; some are well known, such as histamine release and interference in arachidonic acid metabolism (non-steroidal antiinflammatory drugs). Other side effects are the result of local irritation, obstruction or bronchial stenosis. A drug-induced cough could be a consequence of local irritation or of the action of converting enzyme inhibitors on bradykinin catabolism. PMID- 2575363 TI - [Systemic eczematous contact type dermatitis]. PMID- 2575364 TI - Correlation between the effects of rT3 and IMP dehydrogenase inhibitors on normal and trisomic 21 lymphocyte cultures. AB - 3,3'5'-triiodothyronine (rT3) levels have been documented to be low in patients with Down syndrome but the metabolic implications of this finding remain unknown. A highly significant correlation was found between the in vitro variations of the mitotic index in lymphocyte cultures when rT3 or known inhibitors of inosine monophosphate dehydrogenase: mycophenolic acid, 6-mercaptopurine or 2-3 diphosphoglycerate were added. No significant difference was found between the response of trisomy 21 or normal lymphocytes. The finding suggests that rT3 may be a physiological modulator of inosine monophosphate dehydrogenase. The implications on cellular differentiation are discussed. PMID- 2575365 TI - [Transmission cycles of the West-Nile virus in Madagascar, Indian Ocean]. AB - Virological, serological and entomological research conducted in Madagascar since 1975, reveal the wide-spread presence of West-Nile virus on the island. This arbovirus has been isolated from humans, parrots and egrets. Vectors belong to the genus Culex (e.g. Cx. decens, Cx. quinquefasciatus, Cx. antennatus, Cx. univittatus), however the virus has also been isolated from Aedes and Anopheles. Serological tests carried out on over 1,600 human and almost 1,000 animal sera, revealed that human beings could be infected throughout the island. Other potential vertebrate hosts, apart from birds, are oxen and bats. Insectivores, rodents and lemurs are probably involved in the transmission cycles only to a very small extent. PMID- 2575366 TI - [Empirical antibiotic therapy of wounds complicated by anaerobic non-clostridial infection]. AB - Antibacterial activity of 14 drugs against clinical strains of asporogenic anaerobes causing wound infections in the soft tissues i. e. Bacteroides fragilis and Bacteroides melaninogenicus as well as anaerobic gram-positive++ cocci was assayed with the method of serial dilutions in agar. It was shown that among the investigated species B. fragilis had the most marked resistance since out of the 14 drugs only 8 were sufficiently active against it i.e. carbenicillin, levomycetin, lincomycin, dioxidine, metronidazole, thinidazole, nitrazole and erythromycin. The choice of drugs for treating infections caused by B. melaninogenicus and anaerobic grampositive cocci unlike those caused by B. fragilis offered no difficulty since practically++ all the investigated drugs were highly active against the causative agents. There was observed relationship between the frequency of asporogenic anaerobes and the wound genesis. The characteristic features of the species composition connected with localization of the suppurative foci were indicated. The detected specific antimicrobial profiles of the asporogenic anaerobes causing wound infections and the peculiarity of their participation in development of purulent infections of the soft tissues provided a differential approach to empirical antibacterial therapy prior to the pathogen bacteriological investigation and availability of the antibioticograms. PMID- 2575367 TI - [Antihypertensive effectiveness and tolerance of cicletanine. Results obtained with bitherapy]. AB - In a multicentre open trial involving 229 investigators, cicletanine, a new antihypertensive agent, was administered orally in doses of 50 to 100 mg/day either alone (1,238 patients) or combined with another drug (430 patients). In this second group of patients with essential hypertension whose BP had not been normalized by a beta-blocker (n = 157), a calcium inhibitor (n = 67), an angiotensin-converting enzyme inhibitor (n = 134) or an alpha-blocker (n = 7), cicletanine normalized BP (less than 160/95 mmHg) in 48.8% of the patients and significantly lowered BP values which fell from 177.7 +/- 15.9/103.3 +/- 6.3 mmHg to 157.2 +/- 17.6/88.8 +/- 8.7 mmHg. The addition of cicletanine to treatments with beta-blockers, calcium inhibitors and angiotensin-converting enzyme inhibitors normalized BP in 48%, 52% and 47% of patients respectively. A significant reduction of symptoms was noted, notably as regards headache, dizziness, palpitations, lower limb oedema, asthenia, auditory disorders and dyspnoea. The side-effects reported (headache, dizziness, gastralgia, nausea, pruritus) were minor and non-specific; they accounted for the withdrawal of only 8 patients. The only significant, though moderate, biochemical variations observed were decreases in natremia and cholesterolaemia unconfirmed by qualitative analysis. Altogether, cicletanine proved to be effective and well tolerated when administered in combination with other antihypertensive drugs belonging to three main therapeutic classes. PMID- 2575368 TI - [Cicletanine administered with other antihypertensive agents]. AB - The antihypertensive effectiveness and the clinical and biochemical safety of cicletanine were evaluated in 84 patients (28 women, 56 men) presenting with permanent essential hypertension without severe cardiovascular complications. The hypertension was insufficiently controlled by a beta-blocker, a centrally acting antihypertensive drug or nifedipine. After 3 months of treatment during which cicletanine was added to each of these three classes of drugs, there was a significant fall of systolic arterial pressure (-18 mmHg with beta-blockers, -17 mmHg with central agents and -26 mmHg with nifedipine) and diastolic arterial pressure (-22, -21 and -28 mmHg respectively), resulting in normalization of blood pressure (less than 160/95 mmHg) in 63%, 43% and 50% respectively of patients in each therapeutic group. The fall of blood pressure was accompanied by a significant decrease of functional symptoms (headache, palpitations, dizziness); in the nifedipine group, the addition of cicletanine resulted in complete regression of anginal attacks. The therapeutic combinations were well tolerated; only two patients were excluded from the study for undesirable effects unascribable to cicletanine. Otherwise, the side-effects observed were minor. The biochemical values measured did not significantly vary, and the variations noted were of small amplitude. PMID- 2575369 TI - [Evaluation of the effectiveness and tolerance of cicletanine in patients with essential hypertension treated with beta-blockers]. AB - The effectiveness and safety of cicletanine hydrochloride, the first representative of the furopyridine family, were evaluated in a 90-day double blind study involving 120 patients with moderate essential hypertension poorly controlled after at least one month of treatment with a beta-blocker. After a 30 day pre-inclusion period during which a placebo capsule was given together with a stable dose of the beta-blocker, the patients were randomised to one of three therapeutic groups: group 1 (placebo, n = 40), group 2 (cicletanine 50 mg/day, n = 41), group 3 (cicletanine 100 mg/day, n = 39). All three groups were matched in every respect. Eight patients in group I were excluded (5 for ineffectiveness, 2 for unexpected effect, 1 for intercurrent disease) as was 1 patient in group 3 for unexpected effect. On entering the active phase of treatment, supine blood pressures were 171.3 +/- 13.6/103.9 +/- 6.1 mmHg in group 1, 173.5 +/- 12.7/103.6 +/- 5.2 mmHg in group 2 and 171.8 +/- 15.4/104.5 +/- 5.9 mmHg in group 3. A significant (p less than 0.0001) treatment effect on SBP was found in groups 2 and 3 and on DBP in all three groups. The improvement observed in both SBP and DBP was similar in groups 2 and 3 and highly significant when compared with group 1 (p 0.001). At the end of the trial, 5% of group 1 patients, 51.2% of group 2 patients and 74.4% of group 3 patients had normal blood pressure values. The drug was well tolerated clinically and biochemically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575370 TI - Potential histamine H2-receptor antagonists: twin compounds containing diaminofurazan substructure. PMID- 2575371 TI - The differential diagnosis of negative symptoms in chronic schizophrenia. AB - Negative symptoms in schizophrenic patients can have many causes. This paper briefly reviews some of those factors which may contribute to negative symptoms apart from the schizophrenic illness itself. Making these distinctions is crucial for accurate diagnosis, management and prognosis. PMID- 2575372 TI - CNS stimulant controversies. AB - Controversies in the use of central nervous system stimulant medications in children with attention deficit hyperactivity disorder are discussed. Diagnostic issues, age of optimal use, side effects, effects on learning and ethical considerations are current issues. An animal model for the effects of chronic long-term high dose regimes is proposed. PMID- 2575373 TI - Tardive dystonia. AB - Unlike tardive dyskinesia (TD) which is much better known by clinicians, tardive dystonia is a more recently recognised complication of neuroleptic use. It refers to chronic dystonia related to the use of neuroleptic drugs and may be an even more disabling condition than TD. This article reviews its epidemiology, clinical features and treatment aspects, and suggests that it should be separated from TD as a distinct entity. PMID- 2575374 TI - Fast, slow and sudden reductions in fear. AB - An experiment was carried out on 30 spider-fearful and 30 snake-fearful subjects in an attempt to replicate the finding of a correlation between the rapid reduction of fear and the reduced likelihood of significant fear returning after an interval (low return of fear). It was also hoped to observe and closely examine the occurrence of sudden and enduring reductions in fear. The results from the two groups of fearful subjects were reassuringly similar. The fears of both groups were significantly reduced in a relatively brief session, and small but significant returns of fear were observed after a 2 week interval, with the slow responders reporting a higher return of fear than fast responders. The time taken to reduce the fear correlated 0.36 with the return of fear. A minority of subjects did experience a subjectively important, abrupt change in their fears, these 'glass-jar' experiences were associated with faster (overall) reductions in fear, a lower return of fear, and subjective estimates of permanent and generalized reductions of the fear. PMID- 2575375 TI - Breathing retraining, exposure and a combination of both, in the treatment of panic disorder with agoraphobia. AB - The present study investigates the differential effectiveness of three treatment packages for agoraphobia. Patients suffering from panic disorder with agoraphobia (DSM-III-R) received one of three treatments: Breathing Retraining with Cognitive Restructuring (BRCR), graded self-exposure in vivo (EXP), or a combination of BRCR and EXP. Treatments consisted of 8 sessions. Assessment consisted of self report measures for panic, phobic anxiety and avoidance, depression, general anxiety, somatic complaints and fear of body sensations, and of two respiratory measures (respiratory rate and alveolar pCO2). The treatments resulted in a reduction in symptomatology on all self-report measures, except panic frequency, and in a decrease in respiratory rate. There was no evidence for a differential efficacy for any of the treatments on any of the variables. Contrary to expectation, and at odds with findings from earlier studies, BRCR had no significant effect on panic frequency. A detailed comparison of sample characteristics of patients in our study and previous studies, did not yield insight into possible causes for the failure to replicate earlier results. The limited effectiveness of breathing retraining in reducing panic, as observed in the present study, leads us to conclude that the role of hyperventilation in panic is less important than previously thought. PMID- 2575376 TI - Instructions to focus upon or distract from internal cues during exposure treatment of agoraphobic avoidance. AB - Instructions to focus upon feared somatic sensations were compared to instructions to engage in distracting tasks, while practising in vivo exposure to feared agoraphobic situations. Thirty individuals assigned a primary diagnosis of Panic Disorder with moderate to severe Agoraphobia were assigned randomly to one of the two treatment conditions. Assessments were conducted pre, post and 6 months following treatment completion, using subjective, behavioral and clinician rated measures of change. Composite outcome criteria indicated a trend for distracted exposure to yield a higher percentage of improvement than focused exposure, at post assessment. However, focused exposure group members improved to a greater extent over the follow-up interval than members of the distracted group. These trends were relatively weak, given the absence of significant group by time interactions in terms of individual variable analyses. The results were discussed with reference to the role of distraction in fear reduction. PMID- 2575377 TI - Site-specific alteration of Gly-24 in streptokinase: its effect on plasminogen activation. AB - Oligonucleotide-directed mutagenesis was carried out to replace glycine-24 of streptokinase with histidine, glutamic acid, or alanine. Substitutions with either histidine or glutamic acid resulted in almost complete loss of streptokinase activity but streptokinase replaced with alanine retained its activity. Although streptokinases with histidine-24 or glutamic acid-24 bound normally to human plasminogen, they were not able to generate active plasmin, whereas those with alanine-24 or glycine-24 (wild-type) could generate active plasmin. The results indicate that the small, uncharged alkyl group side-chain on the 24th amino acid residue of streptokinase is indispensable for the activity of the human plasminogen-streptokinase complex. PMID- 2575378 TI - Involvement of protein kinase C in activation of human granulocytes and peritoneal macrophages by type 1 fimbriated (mannose specific) Escherichia coli. AB - Specific binding of bacteria to phagocytic cells mediated by antibody and complement (opsonins) or by lectin-carbohydrate interactions is required for their efficient uptake and killing by opsonophagocytosis or lectinophagocytosis, respectively (Ofek and Sharon, Infect. Immun. 56, 539, 1988). An early step in these processes is activation of the phagocytes by the bound bacteria, as evidenced by appearance of an oxidative burst. Previous work has shown that protein kinase C (PKC) is involved in activation of human granulocytes by opsonized Escherichia coli. In the present study, we used three inhibitors of PKC to examine the possible involvement of the enzyme in activation of human granulocytes and peritoneal macrophages by type 1 fimbriated (mannose-specific) Escherichia coli in the absence of opsonins. Activation, as measured by chemiluminescence, was completely inhibited by sphingosine (50 microM) and only partially (50%) by 100 microM H-7 [1-(5-isoquinolinesulfonyl)-2 methylpiperazine]; in both cases it was fully reversible. The third inhibitor, K252a, also inhibited almost completely the activation at 1 microM. The inhibitors acted similarly on activation of the phagocytic cells by opsonized bacteria or by phorbol-12-myristate-13-acetate (0.1 microM). Down regulation of the kinase, by pretreatment of the human granulocytes or macrophages with a high concentration (1.6 microM) of phorbol myristate acetate, abolished their ability to respond to stimulation by the bacteria. Our findings provide evidence for the involvement of PKC in the activation of phagocytic cells by type 1 fimbriated bacteria. PMID- 2575379 TI - beta-Amyloid precursor is a PEST protein. AB - The beta-amyloid peptide is generated by proteolytic processing of a family of beta-amyloid precursor proteins. Here we report that beta-amyloid precursor proteins have a primary structure motif known as a PEST sequence, which is predictive of the class of most protease-sensitive rapidly turning over proteins. Consistent with this, the precursors were extraordinarily susceptible to degradation by the calcium-dependent protease calpain I. The identification of beta-amyloid precursors as PEST sequence-containing proteins has implications for both the normal cellular function of beta-amyloid precursor proteins and the mechanisms regulating their expression and processing. PMID- 2575380 TI - Highly specific inhibition of human immunodeficiency virus type 1 by a novel 6 substituted acyclouridine derivative. AB - A novel 6-substituted acyclouridine derivative, 1-[(2-hydroxy-ethoxy) methyl]-6 phenylthiothymine (HEPT), has proved to be a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) in vitro. HEPT inhibits HIV-1 replication in various T4 cell cultures as well as peripheral blood lymphocytes and macrophages. The 50% antiviral effective concentration for HIV-1 (HTLV-IIIB) in MT-4 cells is 7.0 microM, while the 50% cytotoxic concentration for mock infected MT-4 cells is 740 microM. Although HEPT is inhibitory to various strains of HIV-1, it has no effect on the replication of other retroviruses including HIV type 2. In contrast with the dideoxynucleoside (i.e. azidothymidine) 5' triphosphates, the triphosphate of HEPT does not interact with HIV-1 reverse transcriptase. The mechanism of action of HEPT remains subject of further study. PMID- 2575381 TI - The direct activation of human multidrug resistance gene (MDR1) by anticancer agents. AB - Enhanced expression of a multidrug-resistance gene (MDR1) is observed in some cancer patient, but any regulatory mechanisms of MDR1 gene expression in this phenomenon is not yet known. In this study, the regulation of MDR1 gene was analysed by transient expression assays in the presence of anticancer agents. We found that MDR1 promoter could be activated directly on the addition of anticancer agents including vincristine, daunomycin, adriamycin and colchicine. The results suggest that the level of MDR1 mRNA expression is associated with previous chemotherapy, including drugs that select the multidrug resistance phenotype. PMID- 2575382 TI - Expression of normal and abnormal porcine kidney D-amino acid oxidase in Escherichia coli: purification and characterization of the enzymes. AB - Expression plasmids for normal and abnormal porcine D-amino acid oxidases (E.C. 1.4.3.3, DAO) have been constructed from cloned cDNA that encodes the entire protein sequence of DAO, and the enzymes were expressed in Escherichia coli cells on a large scale. The expressed enzymes were purified to apparent homogeneity. The molecular weight of the normal DAO (38 kD) was identical with that of DAO purified from porcine kidney, whereas that of the abnormal DAO was 39 kD, which comprised the normal DAO with an additional decapeptide at its amino terminus. However, the specific activities of the two enzymes were comparable with that of natural DAO. The results indicate that the bulky decapeptide does not affect the structure necessary for the catalytic function of DAO in the amino-terminal region. The use of a GTG triplet in the 5'-untranslated region of DAO cDNA as the initiation codon for the synthesis of the abnormal DAO is suggested. PMID- 2575383 TI - Atypical multidrug resistance in CCRF-CEM cells selected for high level methotrexate resistance: reactivity to monoclonal antibody C219 in the absence of P-glycoprotein expression. AB - A series of CCRF-CEM sublines selected for extreme resistance to methotrexate has been shown previously to exhibit cross resistance to a number of agents belonging to the multidrug resistance phenotype (J.Natl.Cancer Inst.1989; 81, 1250-1254). The role of the mdr1 gene and its product (P-glycoprotein) in this atypical pattern of multidrug resistance has now been investigated. Southern and Northern analyses failed to demonstrate any amplification, rearrangement or over expression of the mdr1 gene in the drug-resistant cells. Similarly, monoclonal antibodies MRK16 and JSB1 revealed no increase in the amount of P-glycoprotein present. By contrast, monoclonal antibody C219 detected a 170 kDa protein in all sublines, and in highest concentration in the most resistant cells. The results raise the possibility that a novel, C219-reactive protein may mediate resistance to both methotrexate and members of the multidrug resistance family. PMID- 2575384 TI - A protein target site in an early replicated human DNA sequence: a highly conserved binding motif. AB - We have previously reported that a human nuclear factor, probably corresponding to the USF/MLTF protein [1,2], is able to bind specifically to a DNA sequence present in DNA replicated at the onset of S-phase [3]. Here we demonstrate that the same factor binds also to several other similar sequences, present in eukaryotic and viral genomes. Mutations or methylation in a CpG dinucleotide, central in the palindromic binding site, completely abolish binding. Furthermore, we present evidence for the existence of at least two other nuclear proteins in human cells with the same DNA binding specificity. The data presented suggest a strong evolutionary conservation, among distantly related organisms, of the binding motif, which is probably the target of a number of nuclear factors that share the same DNA binding specificity albeit in the context of different functions. PMID- 2575385 TI - Partial agonist activity of celiprolol as assessed in conscious unrestrained dogs in comparison with those of pindolol and labetalol. AB - The effects of celiprolol on the heart rate (HR) and the total peripheral resistance (TPR) were studied in chronically instrumented conscious dogs in comparison with those of pindolol, propranolol and labetalol. Intravenous injection of pindolol, celiprolol and labetalol increased the HR and decreased the TPR dose-dependently, whereas propranolol did not. The ratios of doses that elicited 12% changes in both parameters (HR12/TPR12) were 4.85 +/- 2.63, 0.61 +/- 0.03 and 0.42 +/- 0.11 for celiprolol, pindolol and labetalol, respectively, indicating the preferential reduction of TPR by celiprolol. Changes in HR and TPR produced by these three agents were antagonized by propranolol dose-dependently. However, inhibition by 3 mg/kg of propranolol was incomplete in the cases of labetalol-induced decrease in the TPR at the dose of TPR12 (51%) and celiprolol induced increase in the HR at the dose of HR12 (89%). These results suggest that changes produced by celiprolol as well as pindolol and labetalol were mostly explainable by partial agonist activity via beta-adrenoceptors. However, the contribution of the alpha-blocking activity must also be taken into consideration in the case of the reduction of the TPR by labetalol. In addition, there is a possibility that celiprolol may increase HR via its direct action. PMID- 2575386 TI - [Is there a drug therapy for sero-mucotympanum?]. AB - A critical review of the literature (including the authors' own randomized double blinded studies) does not support the widespread use of drugs for treatment of otitis media with effusion (secretory otitis media).--Neither mucolytic agents, nor decongestants, nor antihistamines have any favourable effect on the course of the disease. Success with steroids or antibiotic agents in selected cases is very limited. PMID- 2575387 TI - Septic arthritis following puncture wound of the foot. PMID- 2575388 TI - Instrumental assessment of lingual motor instability in tardive dyskinesia. AB - Instrumental measurement of fine tongue instability was carried out in 28 psychiatric patients (13 with and 15 without tardive dyskinesia [TD]) and 11 normal controls. All of the 13 TD patients and 4 of the 15 non-TD patients had instability of tongue greater than 2 standard deviations of the normal control mean. The tongue instability correlated with lingual (but not total body) dyskinesia rating and with age in the psychiatric patients. Our findings suggest that spectral analysis of fine tongue position is sensitive to overt as well as subclinical dyskinesia associated with neuroleptic usage. PMID- 2575389 TI - Allosteric regulation of the state of adenylylation of glutamine synthetase in permeabilized cell preparations of Rhodopseudomonas sphaeroides. AB - Following a freeze-thaw cycle, and the treatment of Rhodopseudomonas sphaeroides with the nonionic detergent Lubrol PX, the permeabilized cell suspensions can be assayed directly both for the intracellular levels of glutamine synthetase and the state of adenylylation (i.e. the average number n of adenylylated subunits/dodecameric molecules). It seems that all components of the bicycle system are retained if cells grown with low concentrations of ammonia as the sole nitrogen source are used. The value of n was dependent upon the concentration of substrates (ATP, Pi) and allosteric effectors (ATP, glutamine and alpha ketoglutarate) of adenylytransferase. The value of n affected by UTP, the specific substrate of the uridylyltransferase shows first the evidence that the bicycle cascade control system studied in Escherichia coli may exist in this phototrophic bacterium. PMID- 2575390 TI - Suppression of the response to murine alloantigens: four-cell-type clusters, function-flipping and idiosyncratic responses. AB - Specific immune suppression develops under certain well-defined conditions of exposure to antigen, where it is evident as a diminution of the immune response due to the activity of antigen-specific suppressor cells, usually T cells. Although subject to intensive study over the last two decades, interest in suppression has declined recently because of failure to make progress in defining molecular mechanisms or the precise cells involved. This review outlines present information, and then goes on to present three new ideas that emerge from study of murine alloantigens: (1) how the formation of four-cell-type clusters might mediate suppression; (2) a classification of means whereby class II MHC molecules may mediate suppression that includes a suggestion to account for the anomalous behaviour of H-2Ab; and (3) the value of idiosyncratic responses as probes of suppressor mechanisms. It does not provide an exhaustive coverage review of the literature, but recommends certain other reviews that do so. PMID- 2575391 TI - Insulin-determinant recognition by helper and suppressor T cells. PMID- 2575392 TI - The V-J-intergenic region of the human kappa locus. AB - The 23-kb region between the V kappa and J kappa gene clusters was investigated in some detail. The region was found to be free of V kappa genes or V kappa gene like structures, confirming the previous supposition that the V kappa gene B3 is the J kappa proximal V kappa gene. The B3-J kappa distance of 23 kb was found to be the same in the DNAs of several individuals. A HindIII restriction fragment length polymorphism was detected within this region. A sequence of 533 bp located approximately in the middle of the region has a highly homologous counterpart (called homox) on another chromosome. The two sequences are 96% identical. Possible mechanisms for the generation of such a duplicate are discussed. PMID- 2575393 TI - Biodegradability of synthetic branched polypeptide with poly(L-lysine) backbone. AB - A detailed investigation is reported about the biodegradation of poly[Lys(DL Alam)], m approximately 3, (AK) the common inside area of a branched polypeptide model system developed by our group over the last decade. Enzymatic hydrolysis was carried out by the exopeptidase aminopeptidase M, or the endopeptidase trypsin, or their mixture. Ion-exchange column chromatography, paper electrophoresis and thin-layer chromatography were utilised to achieve separation of metabolites. Breakdown products were identified by the aid of synthetic oligopeptides representing the potential fragments (DL-Ala2, DL-Ala3, Lys(DL Alam), m = 1-3). The kinetics and the degree of enzymatic degradation were determined. The ratio of peptide/amino acid amounts in the hydrolysate was found to be 1.07 after 24 h treatment with aminopeptidase M, 3.0 with trypsin and 1.3 with aminopeptidase - trypsin mixture. The overall results indicated that the proteolysis of AK by an aminopeptidase M and trypsin mixture proceeds stepwise at multiple sites on the polypeptide chain. The degradation is significantly retarded as compared to that of alpha- or epsilon-polylysine. A mechanism of degradation is suggested based on the experimental results. PMID- 2575394 TI - Protective effects of certain natural and synthetic complexans on the toxicity of chromium and tin to a N2-fixing cyanobacterium, Anabaena doliolum. AB - The effects of chromium and tin on survival, growth, carbon fixation, nitrate reduction, ammonia assimilation, and nitrogenase activity of a N2-fixing cyanobacterium. Anabaena doliolum, and their amelioration by synthetic and natural complexans, viz., EDTA, nitrilotriacetic acid (NTA), pyridine dicarboxylic acid (PDA), and citrate, have been studied. Chromium proved to be much more toxic than tin, as it inhibited growth yield (49%), carbon fixation (53%), and nitrate reductase (79%), glutamine synthetase (30%), and nitrogenase activities (77%) at its sublethal concentration, whereas tin induced less inhibition of growth yield (42%), carbon fixation (50%), and nitrate reductase (66%), glutamine synthetase (32.4%), and nitrogenase activities (70%). Despite its inhibitory effects at 10 micrograms ml-1. EDTA supplementation in metal spiked medium counteracted the toxicity of chromium and tin more significantly than NTA, PDA, and citrate. When supplemented with LD50 of Cr, EDTA protected growth, carbon fixation, NR, GS, and N2ase, respectively, by 32.6, 50.0, 33.3, 17.7, and 65.4%. However, EDTA-induced restoration of the above parameters at a sublethal concentration of tin was only 30.2, 50.0, 28.1, 27.7, and 61.5%, respectively. Although NTA and citrate at 10 micrograms ml-1 each were stimulatory to various processes of test cyanobacterium, they were comparatively less effective than EDTA in the amelioration of metal toxicity. On the basis of these observations, a generalized hierarchical sequence of protective efficiency of synthetic and natural complexing ligands may be given as EDTA greater than NTA greater than citrate greater than PDA. It seems plausible that the toxicity of various heavy metals may be regulated by a large array of organic complexing agents of the aquatic environment because they possess various metal binding sites. PMID- 2575395 TI - T cell accessory molecules mediating cell adhesion and signal transduction. PMID- 2575396 TI - T-cell strategies in AIDS vaccines: MHC-restricted T-cell responses to HIV proteins. PMID- 2575397 TI - Markers for progression in HIV infection. PMID- 2575398 TI - A recombinant clone of HIV-1 preferentially transmitted in normal peripheral blood mononuclear cells. AB - To study biologic properties associated with specific regions of HIV-1, a chimera, pHX-JY1, was constructed by exchanging the vif-env region of a Zairian molecular clone (JY1) with that of pHXB2gpt, a full-length biologically active proviral clone of North American origin. Virus was produced by transfection of permissive cells with parental and recombinant clones, and the biologic and molecular properties of these viruses were compared. Virus derived from pHXB2gpt infected phytohemagglutinin (PHA)-activated normal peripheral blood mononuclear cells (PBMC) and CD4+ leukemic T cell lines equally well. In contrast, virus derived from pHX-JY1 was transmitted slowly to both PBMC and cell lines, and the infectivity of pHX-JY1 virus was two orders of magnitude greater for PBMC than for T cell lines. All essential viral genes in the exchanged JY1 vif-env region were intact and functioned comparably to those of the parent clone in transfected COS-1 cells. The findings suggest differences in these regions of the HIV-1 genome may play an important role in differential cell tropism. PMID- 2575399 TI - Downregulation of HLA class I antigens in HIV-1-infected cells. AB - By means of indirect immunofluorescence analysis we investigated the effect of HIV-1 infection on HLA class I surface antigens. We report here that in CD4+ HeLa cells, in H9 cells, and in peripheral T lymphocytes HLA class I antigens are downregulated following infection with HIV-1. The downregulation is effected at a posttranscriptional level since the amounts of HLA class I specific mRNA are similar in infected and uninfected cells. This phenomenon is not only correlated with the state of infection, that is, the presence of P24 of HIV-1 in the cells, but also depends on the time of infection. Upon HLA class I downregulation by HIV infection, the specific lysis of peripheral blood cells by allogeneic CTL is reduced. PMID- 2575400 TI - Accelerated recovery from neuromuscular block. PMID- 2575401 TI - Benorylate hydrolysis by human plasma and human liver. AB - 1. Benorylate (4-acetamido phenyl-O-acetylsalicylate) hydrolysis in vitro by human plasma and by human liver microsomes and cytosol has been investigated. 2. Benorylate was hydrolysed by a route involving initial hydrolysis of the acetyl group to yield phenetsal followed by hydrolysis to paracetamol and salicylate. Hydrolysis via acetylsalicylate was minor. 3. Benorylate was more actively hydrolysed by liver cytosol than microsomes and about 10 times faster than plasma. 4. Following a single oral dose benorylate (4 g) to volunteers only salicylate and paracetamol were detected in the plasma. 5. The therapeutic effects of benorylate appear to be mediated by salicylate and paracetamol. PMID- 2575403 TI - Interspecies pharmacokinetic scaling of metazosin, a novel alpha-adrenergic antagonist. AB - Based on pharmacokinetic data from mice, rats, and rabbits, the prediction of pharmacokinetics of intravenous metazosin in man has been performed. The correlations were based upon allometric scaling of plasma clearance and the volume of distribution at steady-state. A one-compartment body model approximating clinical pharmacokinetics fits well the elimination phase of subsequently measured metazosin concentrations in volunteers. Fitting human pharmacokinetic data to allometric equations enabled us to superimpose pharmacokinetic curves from different species. PMID- 2575402 TI - Multiple XbaI polymorphisms for carrier detection and prenatal diagnosis of haemophilia A. AB - Three XbaI restriction fragment length polymorphisms (RFLPs) can be detected using the factor VIII-intron 22 probe (p482.6) in a XbaI-KpnI double digest of genomic DNA. The XbaI (A) site had been reported by Wion et al (1986) to be in intron 22, while the two additional sites. XbaI (B) and XbaI (C), are shown here to be X-linked and close to the XbaI (A) site. The frequencies of heterozygosity for these three sites are 0.49, 0.18 and 0.30 respectively. In 75 females the observed heterozygosity rate for the XbaI (A) site is 0.41 and this increased to 0.57 with the two additional sites. Care should be exercised when interpreting the XbaI RFLPs, since the 1.4 kb XbaI/KpnI fragment and the 4.8 kb XbaI fragment are associated with both positive XbaI (A) and XbaI (B) sites. By the combined use of the multiple XbaI polymorphisms with the BclI site in intron 18, the carrier detection rate would increase to 67%. Four prenatal diagnoses had been performed using the multiple XbaI polymorphisms. PMID- 2575404 TI - Functional diversity of bioactive peptides in the nervous system itself: "how the brain may understand". AB - The interactions involving cells of the nervous system are a complex form of intercellular communication. Biosynthesis of peptide hormones or active neuropeptides is generally through a precursor which provides increased product choices as a function of the processing pathway. Proteolytic processing as well as other molecular modifications lead to a wide range of mature products which may vary in different tissues even though they are derived from the same precursor. Also the same neuropeptide may exhibit different bioactivities for different target cells. Finally, by means of collective packaging in secretory organelles, a cell may be able by synergism to further broaden its biologic effects. In these ways, what is seen as added complication in the CNS, may be from the point of view of the cell, a successful attempt to increase its survival ability to adapt and influence its bioenvironment. PMID- 2575405 TI - [The role of the neurochemical mechanisms of the medial raphe nucleus in anxiety states formed by various aversive actions]. AB - The experimental studies on rats with microinjections of a number of monoamines and amino acids into median raphe nuclei showed functional importance of neither dofamine nor glutamat but of 5-HT or 5-HT- and GABA-ergic mechanisms of median raphe nuclei formation in anxiety states formed by aversive actions of diverse biological importance. PMID- 2575408 TI - Immunomodulators and feeding regulation: a humoral link between the immune and nervous systems. AB - Cells of the nervous and immune systems have specific receptors for humoral substances that originate in both systems. These elements establish a bidirectional information exchange network between the nervous and immune systems. In particular, neuroregulators (neurotransmitters and neuromodulators) can modulate specific immune system function(s) and immunoregulators (immunomodulators) can modulate specific nervous system function(s). Modulation of immune functions by neuroregulators has been receiving considerable attention; however, modulation of nervous system functions by immunomodulators has been little studied. The presence of immunomodulators in the brain and cerebrospinal fluid may represent local synthesis by astrocytes, microglia, endothelial cells, intrinsic macrophages and blood-derived lymphocytes which cross the blood-brain barrier, or the concentration of substances derived from the peripheral blood. Acute and chronic inflammatory processes, malignancy, and immunological reactions stimulate the synthesis and release of immunomodulators in various cell systems. These immunomodulators have pivotal roles in the coordination of the host defense mechanisms and repair and induce a series of endocrine, metabolic, and neurologic responses. This paper focuses on the effects of immunomodulators (interleukins, tumor necrosis factor, tuftsin, platelet activating factor, and others) on the central nervous system (CNS), in particular, on feeding regulation. It is proposed that an immunomodulatory system regulates food intake by a direct action in the CNS through a specific neuro-immuno interaction. This regulatory system may be operative during acute and chronic disease. PMID- 2575407 TI - Growth inhibition of MXT mammary carcinoma by enhancing programmed cell death (apoptosis) with analogs of LH-RH and somatostatin. AB - BDF female mice inoculated with MXT mammary adenocarcinoma were treated for 30 days with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist D-Trp-6-LH-RH (releasing 25 micrograms/day for 30 days), microcapsules of the somatostatin agonist RC-160 (liberating 25 micrograms/day for one month), or the combination of these peptides. Bilateral surgical ovariectomy was performed in one group which served as an additional control. Tumor volume was measured weekly during the treatment period of 30 days. When tumor volume changes in the treated groups were compared to the corresponding changes in controls, the combination of D-Trp-6-LH-RH and RC-160 was the most effective in inhibiting tumor growth and approached the effect of surgical ovariectomy. At the conclusion of the experiment, tumor weights were also measured. All peptide analogs inhibited tumor weight by 42 to 63%. In the D-Trp-6-LH-RH treated group, ovarian weights and uterine weights decreased by 48% and 52%, respectively, as compared to controls. Histologically, the regressive changes in tumors caused by the treatment with RC-160, D-Trp-6-LH-RH and their combination were characterized by the coexistence of apoptosis (programmed cell death) and coagulation necrosis. The transition of apoptosis into coagulation necrosis was a common finding. The term 'apoptotic index' is proposed for the ratio of tumorous glands containing apoptotic cells. The apoptotic index was higher in the treated groups than in the control. PMID- 2575406 TI - Endocrine effects of combined somatostatin analog and bromocriptine therapy in women with advanced breast cancer. AB - In this pilot clinical trial conducted in 10 postmenopausal women with advanced breast cancer, we evaluated the endocrine effects and toxicity of combined somatostatin analog and dopaminergic therapy in the attempt to suppress both growth hormone (GH) and prolactin (PRL) secretion. The patients' mean age was 63 years (range: 54-77) and the average number of previous treatments was 4.8 +/- 2 (SD). All patients were treated with the somatostatin analog SMS 201-995 (100-200 micrograms s.c. in a.m. and h.s.) and bromocriptine (2.5 mg orally twice a day). During treatment, GH levels following provocative testing (either L-DOPA or insulin-induced hypoglycemia) were suppressed in 7/9 patients. Basal somatomedin S (Sm-C) levels declined in 6/9 women. Both GH and Sm-C levels decreased in 4 patients, while in the remaining 5 only one of the two parameters was lowered on treatment. PRL secretion (during provocative TRH testing) was almost totally abolished in 8/9 patients. The treatment did not affect circulating levels of FSH, LH, E1, E2, E1-S, T4, T3RU, or cortisol. Seven patients experienced no side effects. Nausea occurred in 3, but was severe enough in only one to require discontinuation of therapy. One patient experienced disease stabilization consisting of less than 50% regression of skin nodules and pleural effusion, a decline in CEA titer, and an improved performance status lasting 7 months. We conclude that combined SMS 201-995 and bromocriptine therapy is safe and frequently suppresses GH and PRL secretion. Its role in the treatment of metastatic breast cancer should be tested in patients with less advanced disease. PMID- 2575409 TI - Origin of noradrenergic innervation of the spleen in rats. AB - Noradrenergic (NA) sympathetic innervation of the spleen was examined in young adult Sprague-Dawley rats (200-250 g) following surgical removal of the superior mesenteric-celiac ganglia (SM-CG) and/or bilateral transection of the subdiaphragmatic vagus nerve. Sham-operated and unoperated rats served as controls. NA sympathetic innervation of spleens from sham-operated and unoperated controls, and from vagotomized rats, was qualitatively similar, with fibers distributing to the capsule, trabeculae, vasculature, and parenchyma of the white pulp. Complete ganglionic extirpation resulted in almost total denervation of NA fibers in all compartments of the spleen. High-performance liquid chromatography with electrochemical detection (LCEC) for catecholamines (CA) and quantitative morphometry of the density of NA varicosities confirmed these observations. LCEC revealed a greater than 85% depletion of norepinephrine (NE) in the spleen following superior mesenteric-celiac ganglionectomy. Stereological evaluation of NA varicosities with a point counting method revealed a decline of 99% in the volume density of NA terminals that occurred uniformly in all compartments of spleens from ganglionectomized rats. In addition, stereological analysis revealed a loss of total NA varicosities (approximately 31% decrease) in spleens from sham operated rats. This loss in volume density occurred largely due to a loss in parenchymal fibers (approximately 45% decrease). Bilateral subdiaphragmatic vagotomy blocked the effect on NA innervation produced by the surgical stress of sham operation. Retrograde tracing following injection of either fluorogold or true blue into the spleen, coupled with immunocytochemical localization of tyrosine hydroxylase (TH), demonstrated abundant fluorogold (true blue)-labeled neurons in the SM-CG; many, but not all, of these neurons also were TH-positive. These findings indicate that the SM-CG neurons supply NA innervation to the spleen, providing sympathetic innervation as the second neuron in the classical two-neuron sympathetic chain, and suggest additional non-NA innervation of the spleen as well. This study also suggests that surgical stress of sham operation may alter directly the NA innervation of the spleen, possibly by inducing temporary retraction of NA fibers of the parenchymal compartment, which is likely to reduce the availability of NE for interaction with cells of the immune system that possess adrenoceptors and are present adjacent to NA varicosities in this region.4+ Bilateral vagotomy ameliorated the effects of sham operation on NA innervation; since the vagal nerve does not distribute fibers to the spleen, this effect is likely to occur through altered feedback circuits effecting sympathetic outflow, or through altered neuroendocrine outflow.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2575410 TI - Neuroleptic and anti-depressant drug treatment abolishes conditioned immunosuppression in mice. AB - Mice previously exposed to cyclophosphamide in the presence of saccharin-flavored water will show a decreased antibody response to challenge with sheep erythrocytes if simultaneously they are again given saccharin to drink. These mice also show conditioned taste aversion. Treatment of conditioned animals with chlorpromazine or amitriptyline after challenge with erythrocytes in the presence of saccharin reduced the degree of immunosuppression and, though to a lesser degree, the conditioned taste aversion. PMID- 2575411 TI - Interleukin-1 beta and muramyl dipeptide can prevent decreased antibody response associated with sleep deprivation. AB - A single, brief (8 h) period of sleep deprivation (DEP) was found to suppress secondary antibody response to sheep red blood cells in rats. This decrease could be totally prevented if either interleukin-1 beta (IL-1) or muramyl dipeptide (MDP) was administered at the beginning of the DEP vigil. Twenty-five units of IL 1 or 250 micrograms/kg MDP was found to be immunosuppressive in sleeping rats but, paradoxically, the combination of such doses with DEP alleviated this effect. Increased colonic temperatures associated with antigen and/or adjuvant administration were not related to the differences in antibody levels between sleeping and DEP animals. Activation of hypothalamic dopamine in IL-1-treated rats following DEP suggests that this monoamine transmitter system may participate in the observed protective activity of IL-1. The present findings extend the immune adjuvant effects of both IL-1 and MDP to protection of the host against behaviorally induced immunosuppression. PMID- 2575412 TI - Two management policies for patients after myocardial infarction: Does exercise testing and a more intensive approach make any difference? PMID- 2575413 TI - Diagnostic and therapeutic efficacy of barium meal examination: a prospective evaluation in general practice. AB - OBJECTIVE: To assess the efficacy of barium meal examinations in managing patients with dyspepsia in general practice. DESIGN: Prospective study by questionnaires completed by general practitioners before and within three to six months after the barium meal examination. Information was requested about the patients' symptoms, current treatment, reason for requesting the examination, and the working diagnosis, including degree of certainty and, after the examination, about any change in diagnosis, diagnostic confidence, or management and to determine whether the examination was judged to be helpful or not. SETTING: Inner city health district. PATIENTS: 133 Patients with dyspepsia referred by general practitioners for outpatient barium meal examination, 31 of whom failed to attend for the examination, or refused it on arrival, or did not have fully completed questionnaires. Two patients were not available for follow up. MAIN OUTCOME MEASURES: Prevalence of radiological abnormalities and the influence of the examination result on management, particularly changes in drug treatment. RESULTS: Fully completed pairs of questionnaires were available for 100 patients, 58 of whom were aged below 50. Most of the barium meal reports (64) were to confirm the clinical diagnosis; only 22 were to exclude serious disease. Ninety nine patients were already receiving treatment, with 39 taking an H2 receptor antagonist. Fifty eight barium meal examinations showed abnormalities (31 major abnormalities); there were no cancers and in only 18 patients was the working diagnosis changed as a result of the findings. Although the barium meal result increased management confidence (63 patients) and allayed patients' anxiety (46), changes in management attributed directly to the examination occurred in only 22 patients. Management changes were minor, usually comprising interchange of antacids and H2 receptor antagonists. CONCLUSIONS: Young patients (aged below 50) with dyspepsia are still being overinvestigated. Although barium meal examination improves diagnostic confidence and allays patients' anxiety, fully utilising communication skills at the initial consultation might allay anxiety more economically. PMID- 2575414 TI - Evidence that different regional sympathetic outflows vary in their sensitivity to the sympathoinhibitory actions of putative 5-HT1A and alpha 2-adrenoceptor agonists in anaesthetized cats. AB - 1. An investigation was carried out to determine whether the centrally acting hypotensive drugs whose mechanisms of action are due either to activation of 5 HT1A receptors (flesinoxan, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and urapidil--also an alpha 1-adrenoceptor antagonist) or to activation of alpha 2-adrenoceptors (clonidine and moxonidine) cause differential sympathoinhibition. 2. Cats were anaesthetized with alpha-chloralose and simultaneous recordings were made of whole cardiac, splanchnic and renal nerve activity, blood pressure and heart rate. Cumulative dose-response (i.v.) curves were constructed in separate experiments for the above hypotensive agents on these parameters. 3. Renal nerve activity was found to be more sensitive to the sympathoinhibitory action of flesinoxan and 8-OH-DPAT when compared with cardiac nerve activity, whereas the reverse was observed for clonidine and moxonidine, cardiac being more sensitive than renal nerve activity. Splanchnic nerve activity was similarly affected by all drugs. Furthermore at the highest dose, all drugs tended to cause complete inhibition in all regional sympathetic nerve outflows. 4. Urapidil differed from all the above hypotensive drugs in that it caused a similar degree of sympathoinhibition in all sympathetic outflows at all doses. It is suggested that this may be due to the ability of urapidil to block central alpha 1-adrenoceptors in addition to stimulation of 5-HT1A receptors. PMID- 2575415 TI - Effect of cromakalim on contractions in rabbit isolated renal artery in the presence and absence of extracellular Ca2+. AB - 1. The inhibitory effects of the K+ channel activator, cromakalim, upon contractions to noradrenaline, histamine and caffeine were examined in rabbit isolated renal artery. For comparison, the effects of pinacidil, dazodipine and sodium nitroprusside were also studied in some experiments. 2. In normal Krebs solution, cromakalim (1 microM) produced a 39.1% reduction in area under the curve (AUC) of the noradrenaline concentration-response, and a 61.8% reduction in the histamine AUC. Ca2+ removal (with EGTA 0.1 mM) gave an 80.0% reduction in the noradrenaline AUC and a 74.5% reduction in the histamine AUC. The combination of Ca2+ removal and cromakalim (1 microM) had no further effect on the noradrenaline responses (a reduction of 78.4% in AUC), but produced a significantly greater reduction in the histamine AUC (86.2%). 3. LaCl3 (1 mM) reduced the noradrenaline AUC by 74.8% and gave an 81.8% reduction in the response to a single (EC90) histamine concentration. LaCl3 (1 mM) plus cromakalim (1 microM) produced no further reduction in the noradrenaline AUC (71.9%) but gave a significant further reduction of the histamine response (94.6%). 4. Pinacidil (3 microM) reduced the noradrenaline AUC by 35.5%. Pinacidil (3 microM) plus LaCl3 (1 mM) produced the same reduction in the noradrenaline AUC (80.9%) as LaCl3 alone (80.9%). 5. In both normal and Ca2+-free Krebs solution, cromakalim (0.1, 1.0 and 10 microM) produced concentration-related inhibition of the contraction to caffeine (10 mM). This inhibition was antagonised by the K+ channel blocker, glibenclamide (3 microM). Similarly, pinacidil (0.3, 3.0 and 30 microM) produced a glibenclamide sensitive inhibition of the caffeine contraction. At equi-vasorelaxant concentrations, dazodipine (0.01, 0.1 and 1.O microM) and sodium nitroprusside (0.03, 0.3 and 3.0 microM) had no significant effect on caffeine contractions. 6. The data show that the K+ channel activators, cromakalim and pinacidil, unlike the Ca2+ channel blocker, dazodipine, or the guanylate cyclase activator, sodium nitroprusside, can inhibit the contraction which results from caffeine-induced Ca2+ release. Cromakalim and pinacidil, however, inhibit only the component of the noradrenaline response resulting from Ca2+ influx (tonic component) and not that resulting from Ca2 + release (phasic component). Cromakalim may affect both components of the histamine contraction. PMID- 2575418 TI - Neuropeptide Y modulates non-adrenergic, non-cholinergic neural bronchoconstriction in vivo and in vitro. PMID- 2575416 TI - Direct evidence for the atypical nature of functional beta-adrenoceptors in rat adipocytes. AB - 1. The nature of the rat epididymal adipocyte beta-adrenoceptor was investigated by studying the effects of beta 1- and beta 2-selective antagonists on lipolysis induced by (-)-isoprenaline and the lipolytically selective agonist BRL 37344. 2. From 10 nM to 10 microM, the potent and highly selective beta 1-adrenoceptor antagonist CGP 20712A did not influence the concentration-response curve (CRC) of BRL 37344 whereas small but consistent shifts to the right of the (-) isoprenaline-induced CRC were observed. Clear rightward shifts of the CRCs induced by both (-)-isoprenaline and BRL 37344 were produced only at 100 microM CGP 20712A with the corresponding pA2 values being 4.80 and 4.61, respectively. 3. When the beta 2-selective antagonist ICI 118,551 was used at 10 microM and higher, clear and concentration-dependent shifts to the right of the CRCs of both agonists were observed. The slopes of the Schild plots did not deviate significantly from unity, the pA2 values being 5.49 and 5.33 against (-) isoprenaline and BRL 37344, respectively. 4. The results demonstrate that (-) isoprenaline-induced lipolysis in rat white adipocytes is mediated predominantly by atypical beta-adrenoceptors, whereas the typical beta 1-adrenoceptors play a small, subordinate role. The lipolytically selective agonist BRL 37344 acts solely through atypical beta-adrenoceptors. PMID- 2575417 TI - Local application of omega-conotoxin GVIA to sympathetic nerve terminals in the guinea-pig isolated vas deferens. AB - Staphylococcus aureus 502A was grown in the presence of one-third of the minimal inhibitory concentration of clindamycin. Phagocytosis of the antibiotic-treated bacteria by human polymorphonuclear leukocytes was significantly enhanced, compared with that of the untreated control (P less than 0.001). Study of opsonization kinetics by a chemiluminescence assay demonstrated that clindamycin treated staphylococci were opsonized more rapidly than control bacteria and that the serum concentration required for sufficient opsonization was lower. Complement was consumed much faster, and the opsonic fragment C3b was fixed more rapidly to the bacterial surface when the staphylococci were preincubated with clindamycin. Electron micrographs showed an alteration of the staphylococcal cell wall after clindamycin treatment. PMID- 2575419 TI - Effects of clozapine and other neuroleptics on binding of [3H]-Q ICS 205-930 to central 5-HT3 recognition sites. PMID- 2575420 TI - The effects of l-vesamicol on transmitter release from rat motor nerve terminals at high frequencies of nerve stimulation. PMID- 2575421 TI - Paradoxical intervention. PMID- 2575422 TI - Drug treatments of dementia. AB - Present drug treatments for the more common types of dementia are largely palliative or symptomatic, but the promise of drugs to prevent the development of dementia does not seem unrealistic. Neuropharmacological strategies that aim to improve behavioural or cognitive symptoms in dementia are subdivided into drugs that modify central cholinergic, serotonergic, dopaminergic, GABAnergic, and peptidergic transmission. There are no clear clinical guidelines for the management of demented patients who are also hypertensive. The early identification of patients with incipient dementia, the detection of slight but theoretically important beneficial effects, the optimum method of drug administration, more soundly based treatment of behavioural symptoms, and the evaluation of drug combinations are all identified as areas requiring further research. PMID- 2575423 TI - Correlates of positive and negative schizophrenic syndromes in Nigerian patients. AB - The two-syndrome concept of schizophrenia was investigated in a sample of 70 Nigerian schizophrenic patients. The positive and negative syndromes were studied in relation to demographic, historical, neurological and psychometric measures. The negative syndrome was associated with cognitive impairment, behavioural deterioration and left eye dominance, and also with poor pre-morbid educational achievement and longer length of current stay in hospital. The positive syndrome was unrelated to any of the independent variables. The two syndromes were not significantly related, supporting the view that they represent relatively independent dimensions of pathology. This provides further support for the validity of the Type I-Type II subtyping of schizophrenia in populations of patients from different cultural backgrounds, and suggests that the negative syndrome is related to the presence of neurodevelopmental deficits that possibly antedate the schizophrenic illness. PMID- 2575424 TI - Brief intermittent neuroleptic prophylaxis for selected schizophrenic out patients. PMID- 2575425 TI - Lipopigment in the CNS. PMID- 2575426 TI - Tardive dystonia. PMID- 2575427 TI - Depression-dependent exacerbation of TD. PMID- 2575428 TI - Fertility after orchiopexy for cryptorchidism: a new approach to assessment. AB - Fifty-six patients treated surgically for cryptorchidism between 1950 and 1975 were assessed for fertility. Their age at the birth of their first child was used as the parameter. A direct comparison with the normal population of different regions was available from the General Register Office of Scotland, obviating the need to use female statistics for comparison. The results showed that only very late surgical treatment of unilateral cryptorchidism affected fertility. PMID- 2575429 TI - The inner ear of the common rhea (Rhea americana L.). AB - The morphology of the inner ear in rheas was examined by light and electron microscopy. The shape is typically bird-like with very long semicircular canals. The anterior and posterior cristae have small septa cruciata. The vestibular sensory epithelia contain two main types of hair cell innervation; bouton innervated hair cells and calyceal hair cells characterized by a surrounding nerve calyx. The utricular macula has a single zone of calyceal hair cells, while all other previously examined birds, except the mute swan, have 2 zones. The height of the tallest sensory hairs of the cristae is 20-30 microns. In the utricular and lagenar macula, the hairs are 5-7 microns in the striola and 10-20 microns in the main parts of the sense organs. Along the edges of the maculae the longest hairs may reach 20-30 microns. The number of stereovilli on mature vestibular hair cells is 40-60. The sensory hairs of the hearing organ, the basilar papilla, are generally shorter but more numerous than the vestibular sensory hairs. In the proximal end, the tallest of the 175-200 stereovilli are 2.8-3.7 microns; in the distal end of the papilla, the number of stereovilli decrease to 65-100, and their height increases gradually to 7.3-8.7 microns. The neural sensory hairs are generally taller than those of the abneural side. PMID- 2575430 TI - Tyrosine hydroxylase immunoreactivity in a subpopulation of granule cells in the olfactory bulb of teleost fish. AB - The distribution of tyrosine hydroxylase (TH)-like immunoreactivity in the olfactory bulb was studied in three species of teleosts, the tench Tinca tinca, the Mediterranean barbel Barbus meridionalis and the rainbow trout Salmo gairdneri, by using an indirect immunoperoxidase method. The antiserum used displayed a characteristic pattern of immunostaining in the three species, and four main conclusions can be drawn: (1) there is a large population of TH-like positive cell bodies and fibers in the olfactory bulb in fish, mainly in the granule cell and plexiform layers; (2) the immunolabeled cells are identified as granule cells, but only one group of granule cells is positive; (3) specific quantitative variations exist in the pattern of TH immunoreactivity, with use of the same fixative, antibody and localization method, among the three species studied, and (4) the pattern of TH immunoreactivity in the olfactory bulb in teleosts is completely different from that described previously in amniotes. PMID- 2575431 TI - Glutamate-immunoreactivity in the retina and optic tectum of goldfish. AB - Glutamate was immunohistochemically localized in the goldfish retina and tectum at the light and electron microscopic (E.M.) levels using double affinity purified antisera against glutaraldehyde conjugated L-glutamate. In retina, glutamate-immunoreactivity (Glu+) was observed in cone inner segments, cone pedicles, bipolar cells, a small number of amacrine cells and the majority of cells in the ganglion cell layer. The latter were shown to be ganglion cells by simultaneous retrograde labeling. Centrally, Glu+ was observed in axons in the optic nerve and tract, and in stratum opticum and stratum fibrosum et griseum superficialis (SFGS) of the tectum. The Glu+ in the optic pathway disappeared four days after optic denervation and was restored by regeneration without affecting the Glu+ of intrinsic tectal neurons. In tectum, Glu+ was also observed in torus longitudinalis granule cells, toral terminals in stratum marginale, some pyramidal neurons in the SFGS, multipolar and fusiform neurons in stratum griseum centrale, large multipolar and pyriform projection neurons in stratum album centrale, and many periventricular neurons. Glu+ was also localized within unidentified puncta throughout the tectum and within radially oriented dendrites of periventricular neurons. At the E.M. level, a variety of Glu+ terminals were observed. Glu+ toral terminals formed axospinous synapses with dendritic spines of pyramidal neurons. Ultrastructurally identifiable Glu+ putative optic terminals formed synapses with either Glu+ or Glu- dendritic profiles, and with Glu- vesicle-containing profiles, presumed to be GABAergic. These findings are consistent with the hypothesis that a number of intrinsic and projection neurons in the goldfish retinotectal system, including most ganglion cells, may use glutamate as a neurotransmitter. PMID- 2575432 TI - The role of N-methyl-D-aspartate receptors in the generation of short-term potentiation in the rat hippocampus. AB - The effects of stimulus intensity and the N-methyl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonovalerate (AP5) were studied on the induction of short-term potentiation (STP) and long-term potentiation (LTP) in CA1 of the rat hippocampal slice. A tetanus of very weak intensity stimuli produced STP, and also LTP providing the stimuli were applied in the form of a series of high frequency trains rather than one continuous train. Increasing the intensity of the stimuli to just threshold for spike initiation produced larger amplitude STP and LTP. AP5 strongly inhibited the STP as well as the LTP produced by a series of high frequency trains, indicating a large component of this STP was generated by activation of NMDA receptors. A further residual component of STP in AP5, which was associated with a decrease in paired pulse facilitation, is probably generated by a presynaptic increase in the probability of transmitter release. PMID- 2575433 TI - Acetylcholine causes nicotinic depolarization in rat dorsal motor nucleus of the vagus, in vitro. AB - Action of acetylcholine (ACh) on the electrophysiologically identified preganglionic neurons in the dorsal motor nucleus of the vagus (DMV) were investigated in slice preparations of rat medulla oblongata by using conventional intracellular recording technique. Applications of ACh to the DMV neurons resulted in a marked depolarization, which was not abolished in Ca-free superfusing solution, indicating the direct action of ACh on the cells. This depolarization was associated with an increase in membrane conductance and markedly reduced in the Na-free superfusate. The extrapolated reversal potential of ACh response was about -35 mV, indicating that both sodium and potassium conductances are likely responsible for the ACh depolarization. Application of nicotine caused similar depolarization to that of ACh, while muscarinic agonists (muscarine and oxotremorine) did not have any effect. Additions of the nicotinic antagonists hexamethonium and D-tubocurarine to the bathing solution reversibly attenuated the ACh-induced depolarization, while the muscarinic antagonist atropine did not have any effect. The nicotinic properties of ACh action in the DMV neurons presented here form a striking contrast to previous autoradiographic findings. Though endogenous cholinergic inputs to the DMV have not been identified, ACh may have a strong influence on vagal control by depolarization through nicotinic receptors of the DMV preganglionic neurons. PMID- 2575434 TI - Glutamate in the spinal sympathetic intermediolateral nucleus: localization by light and electron microscopy. AB - Glutamate immunoreactivity was examined in the sympathetic intermediolateral nucleus (IML) of the thoracic spinal cord using an antibody (Hepler et al., J. Histochem. Cytochem., 36 (1988) 13-22) to hemocyanin-conjugated L-glutamate and the peroxidase-antiperoxidase (PAP) technique. Glutamate labeling was seen in punctate varicosities throughout the IML, in IML neurons and their dendritic processes extending into the lateral funiculus, and diffusely in the IML neuropil. Glutamate labeling was unaffected by preabsorption of the antibody with a conjugate of L-aspartate (100 micrograms/ml) to bovine serum albumin (BSA), but was abolished by similar treatment with a conjugate of L-glutamate (1.7 microgram/ml) to BSA. Glutamate immunoreactivity in the IML was eliminated caudal to T3 spinal transection, while that in the dorsal horn was preserved. Ultrastructural examination of the IML revealed that glutamate was localized within round clear vesicles in axon terminals ranging in diameter from 0.6 to 2.5 microns, and containing several mitochondria, but no dense-core vesicles. Glutamate-containing terminals made primarily asymmetric synapses on small dendrites of IML neurons. These synapses were usually enveloped by processes of astrocytic glia which could also contain glutamate immunoreactivity. The findings provide an anatomic substrate for glutamatergic excitation of sympathetic nerve discharge through a descending spinal pathway terminating in the IML. These data support the hypothesis that sympathoexcitation elicited by stimulation of the rostral ventrolateral medulla may be mediated by a direct glutamatergic pathway to the IML. PMID- 2575435 TI - Potentiation of [3H]inositol phosphate formation by receptor activation and membrane depolarization in brain cortical slices (I). AB - Potentiation of [3H]inositol phosphate ([3H]IP) accumulation by receptor agonists combined with depolarizing agents was studied in rat brain cortical slices, prelabeled with [3H]inositol. Muscarinic agonists, alpha 1-adrenergic, histaminergic and serotonergic agonists remarkably enhanced (2-7-fold) the accumulation of [3H]IP in the presence of KCl (30 mM). The potentiated levels of [3H]IP were strongly dependent on K+ concentration and displayed a dose-response relationship with the agonist. Other depolarizing agents such as veratridine and ouabain induce potentiation of [3H]IP formation similarly to that observed by KCl, but to a lesser extent. The production of elevated levels of [3H]IP is Ca2+ dependent with maximal effect at 0.6 mM which is similar to the Ca2+ dependency observed for the agonist and the depolarizing agent alone. Enhanced [3H]IP levels induced by agonists in the presence of depolarizing agents affect Vmax values only, since the apparent half maximal effective concentration of carbachol (CCh) induced-IP-formation (1.2 x 10(-4) M) and of the phenylephrine-induced IP formation (8 x 10(-6) M), were not affected in the presence of either K+ or veratridine. In addition the efficacy of various muscarinic agonists as inducers of IP-accumulation was conserved under depolarizing conditions as compared to IP accumulation under normal conditions. In the presence of KCl (30 mM) the maximal degree of potentiation was at a range of 5-7-fold, with order efficacy of ACh greater than CCh greater than Oxo M greater than arecoline much greater than pilocarpine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575437 TI - Basal forebrain and mesopontine tegmental projections to the reticular thalamic nucleus: an axonal collateralization and immunohistochemical study in the rat. AB - Using a double fluorescence retrograde labeling procedure, the present study sought to determine the degree to which basal forebrain and mesopontine tegmental neurons have axons that innervate both the reticular thalamic nucleus and the cerebral cortex. Immunofluorescence for choline acetyltransferase, somatostatin, and the calcium-binding protein parvalbumin was also performed to elucidate the neurochemical identity of basal forebrain and mesopontine tegmental inputs to the reticular thalamic nucleus. A significant portion (10-15%) of neurons in the basal forebrain and mesopontine tegmentum that were retrogradely labeled from the reticular thalamic nucleus were also found to be retrogradely labeled from the cortex. Many of these neurons stained positively for choline acetyltransferase. Of the basal forebrain neurons retrogradely labeled from the reticular thalamic nucleus, approximately 20% were found to be immunoreactive to choline acetyltransferase, whereas none was stained for somatostatin. A larger portion (up to 50%) of the basal forebrain neurons that were retrogradely labeled from the reticular thalamic nucleus were parvalbumin-immunoreactive, and some of these were also retrogradely labeled from the cortex. These results suggest that a subpopulation of cholinergic and non-cholinergic neurons in the basal forebrain and the mesopontine tegmentum may influence simultaneously the activity of neurons in the reticular thalamic nucleus and the cerebral cortex. PMID- 2575436 TI - Neuronotoxic effects of monoclonal anti-Thy 1 antibody (OX7) coupled to the ribosome inactivating protein, saporin, as studied by suicide transport experiments in the rat. AB - As a first attempt to develop suicide transport agents based upon antineuronal antibodies, we studied an immunotoxin directed against the Thy 1 antigen which is on rat neurons. The immunotoxin was composed of mouse monoclonal anti-Thy 1 antibody (OX7) and the ribosome-inactivating protein, saporin, and was prepared using the heterobifunctional cross linker, SPDP, which provides a disulfide linkage between the two protein components. This immunotoxin reliably and selectively destroyed ipsilateral vagal motor and sensory neurons after injection into the cervical vagus. Injection of the immunotoxin into the caudate nucleus produced destruction of the ipsilateral substantia nigra, pars compacta and intralaminar thalamic nuclei (parafascicular and central median). Anti-mouse IgG immunoperoxidase staining confirmed axonal transport of OX7 by vagal sensory and motor neurons and by caudate afferents and efferents. Systemic toxicity was not observed with OX7-saporin. The neuronotoxic effects of OX7-saporin were specific since injections of a similarly constructed immunotoxin of irrelevant specificity or a mixture of OX7 and saporin were without suicide transport activity. These results show the feasibility of using immunotoxins as suicide transport agents. PMID- 2575438 TI - MIF-1 and Tyr-MIF-1 augment muscimol-stimulated chloride uptake in cerebral cortex. AB - The peptides MIF-1 (Pro-Leu-Gly-NH2) and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) recently have been found to augment the effects of gamma-aminobutyric acid (GABA) on benzodiazepine receptor binding and chloride channel binding (Tyr-MIF-1) at the GABAA receptor complex. To determine whether these peptides affect the function of this complex in chloride transport, we evaluated chloride uptake stimulated by the GABA analog muscimol in synaptoneurosome preparations. In mice treated with either MIF-1 or Tyr-MIF-1 (1 mg/kg IP), maximal chloride uptake in cortex was increased compared with controls. The two peptides had similar effects in cortical preparations, but in cerebellum neither peptide altered chloride uptake. No differences from controls were observed in cortical synaptoneurosomes treated in vitro with either MIF-1 or Tyr-MIF-1. These results suggest that the brain peptides MIF-1 and Tyr-MIF-1 alter function at the GABAA receptor complex, perhaps by binding at a specific peptide receptor. PMID- 2575439 TI - The paradox of alpha 2 adrenergic regulation of prolactin (PRL) secretion. I. The PRL-releasing action of the alpha 2 receptor agonists. AB - Systemic (IV) administration of the alpha 2 receptor agonist clonidine is known to stimulate secretion of PRL and growth hormone (GH) suggesting a stimulatory role of the central alpha 2 receptors in the regulation of the two hormones. The present work confirms this notion for GH but indicates that the alpha 2 agonists stimulate PRL release by a peripheral action not involving central alpha 2 receptors. This conclusion is based on the following findings: 1) The minimum effective IV dose of clonidine or UK 14304 was four times larger for activation of PRL than GH secretion and had already manifest extracentral effects (elevation of arterial BP). 2) Subcutaneous injection of UK 14304 (220 micrograms/kg) elevated plasma GH but not PRL levels indicating that an effective activation of the central alpha 2 receptors does not stimulate PRL release. 3) Peripherally acting alpha 2 agonists (p-aminoclonidine, oxymetazoline) had no effect on GH secretion but stimulated PRL release in a manner identical with the effect of clonidine or UK 14304. 4) The peripherally acting alpha 2 antagonist DG-5128 blocked only the PRL secretory response to UK 14304 whereas the peripherally and centrally active yohimbine blocked the PRL and GH responses. PMID- 2575440 TI - The paradox of alpha 2 adrenergic regulation of prolactin (PRL) secretion. II. PRL-releasing action of the alpha 2 receptor antagonists. AB - It has been suggested that the stimulation of the secretion of PRL by the alpha 2 adrenergic receptor antagonists (yohimbine, piperoxane) results from blockade of an inhibitory influence imposed on PRL release by the central alpha 2 receptors (7, 15). Our present results do not support these conclusions for the following reasons: 1) The effectiveness of the alpha 2 receptor antagonists yohimbine (YOH), rauwolscine (RAU), Wy 26392 and idazoxan (IDAZ) respectively to activate secretion of PRL was not related to their alpha 2 antagonist potencies. RAU was more effective in activation of PRL secretion than either YOH or Wy 26392 although it had a similar alpha 2 antagonist activity, while IDAZ, the most potent alpha 2 blocker among the four compounds, did not stimulate PRL secretion. 2) The PRL-releasing effect of YOH or Wy 26392 was reversed by the alpha 2 agonist clonidine but the same effect of RAU was not, speaking against a common alpha 2-mediated mechanism of action of the three antagonists. 3) The PRL stimulating effect of YOH, RAU or Wy 26392 persisted following inhibition of NE synthesis and presumably release with FLA 63, DDC or combination of reserpine and DDC. 4) Conversely, we found no indication for an inhibiting influence of activation of the alpha 2 receptors on the secretion of PRL. We conclude that the stimulation of PRL secretion by the alpha 2 receptor antagonists is not derived from blockade of the central alpha 2 receptors but from other, not yet defined properties of the drugs. PMID- 2575441 TI - Passage of Tyr-MIF-1 from blood to brain. AB - Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) has been shown to be transported from the brain to blood by a saturable system shared with Met-enkephalin and a few other substances. It is not known whether a similar system exists in the opposite direction. Accordingly, the entry rate of 125I-Tyr-MIF-1 from blood to brain was measured by a method involving perfusion of the test substances into the common carotid artery. The rate of entry was obtained from the slope of the line determined by brain to blood ratios at multiple points of time. Penetration of 125I-Tyr-MIF-1 across the blood-brain barrier was found to be 4.444 x 10(-3) ml/g/min, an entry rate significantly higher than that of the vascular marker 125I-albumin. Competition with Tyr-MIF-1 or nonradioactively labeled 127I-Tyr-MIF 1 showed no difference in rate of entry, indicating that the penetration of 125I tyr-MIF-1 was not saturable. Met-enkephalin and Leu-enkephalin also failed to affect entry of 125I-Tyr-MIF-1. The results indicate that Tyr-MIF-1 can enter the brain from the blood to a greater extent than does albumin, but that this penetration does not involve a saturable system. PMID- 2575442 TI - Differential effects of Tyr-MIF-1 and naloxone in two animal models involving benzodiazepine. AB - It has been shown previously that the endogenous brain peptide Tyr-MIF-1 (Tyr-Pro Leu-Gly-NH2) can act as an antiopiate and can also increase binding and function at the GABAA/benzodiazepine receptor complex. We now describe the effects of this tetrapeptide in two models in which the antiopiate naloxone has been reported to decrease the activity of benzodiazepines. Unlike naloxone, Tyr-MIF-1 and MIF-1 neither prevented chlordiazepoxide-induced locomotor hyperactivity in mice on a tilting floor nor suppressed chlordiazepoxide-induced eating in rats. Thus, in these two systems, Try-MIF-1 did not act as an antiopiate or alter the effects of a benzodiazepine, indicating a selectivity in the actions of Tyr-MIF-1. PMID- 2575443 TI - Contribution between dorsal and ventrolateral regions of medulla oblongata in vasomotor function of cats. AB - In cats anesthetized with alpha-chloralose and urethane, the medulla oblongata was explored with electrical and/or chemical stimulation for vasopressor actions. Chemical stimulation included semimicroinjection of sodium glutamate or microinjection of dl-homocysteic acid (DLH). The dorsal (DM), particularly its dorsomedial (DMM) portion, and the ventrolateral (VLM) regions were found to be most sensitive to both electrical and chemical stimulation. In between these two regions there was an area in the ventral portion of the gigantocellular and the parvocellular reticular nuclei that was sensitive to electrical and somewhat sensitive also to chemical stimulation. The responses to chemical stimulation indicate the existence of perikarya in these three areas for vasopressor actions. The most active response of VLM followed microinjection of DLH into the region of nu. paragigantocellularis lateralis (PGL) and subretrofacial nu. These responses were about 30% greater than those from DM where the most active area was found in the DMM region including the nu. and tractus solitarius. When an extensive area of VLM was lesioned bilaterally with kainic acid (KA, 1 micrograms/100 nl), the resting systemic arterial blood pressure (SAP) fell 42% and the pressor response on DM stimulation fell by more than 80%. In contrast, after similar KA bilateral destruction of DM the resting SAP fell 38% and the pressor responses from 67%. When only a limited area in the PGL/subretrofacial nu. of the rostral VLM (3-4 pressor sites, 1 mm apart) on one side was lesioned, the resting SAP remained unaltered while the pressor response on the ipsilateral DMM decreased 76%. On the other hand, when a similar smaller KA lesion (3-4 sites) was made in the DMM, although the resting SAP did not change, the pressor response on stimulation of the ipsilateral rostral VLM decreased 28%. Further lesioning of the contralateral DMM then decreased the rostral VLM pressor response 62% without much alternation in the resting SAP. Results of the present experiments are in accordance with our previous results that neuronal perikarya for vasopressor action exist not only in VLM but also in DM (18,34) with the function of VLM slightly predominant over DM. It seems highly possible that reciprocal innervation exists between DM and VLM, at least between DMM and the PGL/subretrofacial nu. region. PMID- 2575445 TI - In vitro studies of Tyr-MIF-1 with human lymphocytes. AB - Our previous report showed that the brain peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) blocks the inhibitory effect of morphine sulfate on E-rosette formation by human peripheral blood lymphocytes (PBL). In this study, additional in vitro effects of Tyr-MIF-1 on human PBL were studied. The percentages of positive cells for CD 2, a sheep erythrocyte receptor, CD 4 and CD 8 were unchanged after incubation of PBL with morphine or morphine plus Tyr-MIF-1. Tyr-MIF-1 was not mitogenic by itself. The addition of Tyr-MIF-1 did not increase the proliferative response of PBL to Con A, although morphine did. Tyr-MIF-1 did not activate PBL to produce IL 2 nor did it affect the production of IL 2 by Con A-stimulated PBL. The results suggest that Tyr-MIF-1 does not directly modulate CD 2, CD 4 and CD 8 expression, does not alter the proliferative response of PBL, and does not affect the production of IL 2. PMID- 2575444 TI - Serotonin microinfusion into the ventral tegmental area increases accumbens dopamine release. AB - The effects of microinfusion of serotonin (5-HT) agents as well as glutamate and muscimol into the ventral tegmental area (VTA) on dopamine (DA) release in the ipsilateral nucleus accumbens (ACC) were investigated in freely moving rats, using a push-pull perfusion procedure. The baseline values for DA, 3,4 dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5 hydroxyindoleacetic acid (5-HIAA) were approximately 0.24, 8.4, 2.1 and 2.7 pmol/15 min, respectively, in the push-pull perfusate of the ACC. When microinfused into the VTA, glutamate (0.74 microgram) significantly (p less than 0.05) increased the contents of DOPAC (110%) and HVA (90%) over baseline levels in the perfusate. On the other hand, 0.5 microgram muscimol (a gamma-amino-n butyric acid, GABA, agonist) significantly, (p less than 0.05) decreased both DA (40%) and DOPAC (20%) levels relative to baseline values. Administration of 2 micrograms 5-HT into the VTA caused a significant (p less than 0.05) elevation in the perfusate levels of DOPAC (80%) and HVA (70%) over baseline values. A similar effect was obtained with a nonselective 5-HT1 agonist but not with a selective 5 HT1A agonist. The results suggest that 5-HT innervations in the VTA may have an excitatory action possibly via 5-HT1B rather than 5-HT1A receptors on the mesolimbic DA system projecting to the ACC and that this DA system may also be regulated by glutamatergic and GABAergic (via GABAA receptors) inputs. PMID- 2575446 TI - Effect of ganglionic stimulating and blocking agents on the fast components of colonic myoelectrical activity in the rat. AB - The presence of two types of fast myoelectrical activities, medium fast activity and fast activity, has been demonstrated previously in the electromyogram of colon in normal children and in the rat by the authors. An absence of medium fast activity in Hirschsprung's disease and in experimental aganglionosis of colon in the rat has also been described. In the present study the fast components of colonic myoelectrical activity were analysed during the procedures affecting ganglionic transmission. It was observed that ganglionic stimulants, such as balloon inflation, and intra-arterial injections of acetylcholine and small amounts of nicotine, increased the spike activity and the frequency of medium fast activity without affecting fast activity. The intra-arterial injections of ganglionic blocking agents, such as nicotine in large amounts and pentolinium tartrate, completely abolished the medium fast activity. These observations suggest that the ganglionic activity is responsible for the genesis of medium fast activity and that the absence of cholinergic ganglionic transmission is the most important single factor for the reported altered electromyogram pattern in aganglionosis. PMID- 2575447 TI - Altered release of growth hormone from dispersed adenohypophysial cells of streptozotocin diabetic rats. I. Effects of growth hormone releasing factor and somatostatin. AB - As growth hormone has been implicated in the "dawn phenomenon," an early morning rise in serum glucose, we have studied the control of growth hormone release in diabetes using an acutely dispersed system of adenohypophysial cells from normal or diabetic rats (65 mg/kg streptozotocin, 8 days before sacrifice; serum glucose, 490 +/- 17 mg/dL). Growth hormone release is normally controlled by the two hypothalamic hormones, growth hormone releasing factor and somatostatin. We have found cells of the diabetic rats exhibit changes in sensitivity that result in increased growth hormone release in static incubation. In normal cells, rat growth hormone releasing factor increases growth hormone release three- to four fold with an EC50 of 151 +/- 27 pM (n = 7). In contrast, in cells from diabetic rats, there was a significant (twofold) increase in sensitivity to growth hormone releasing factor (EC50 = 75 +/- 15 pM, n = 7) which resulted in increased growth hormone release with lower but not maximal (10 nM) growth hormone releasing factor. Basal nonstimulated release was unchanged. Somatostatin inhibition of stimulated growth hormone release was reduced (n = 7); half-maximal inhibition occurred with 0.21 +/- 0.03 nM (normal) and 0.76 +/- 0.17 nM somatostatin (diabetic). In perifusion the peak secretion rate was significantly lower for diabetic cells stimulated by a maximal dose of growth hormone releasing factor. These studies suggest somatotrophs of diabetic rats have altered sensitivity in vitro to the controlling hormones growth hormone releasing factor and somatostatin. PMID- 2575448 TI - National childhood injury prevention conference. PMID- 2575449 TI - Hypersexuality with antiparkinsonian therapy. AB - Thirteen parkinsonian patients drawn from two large parkinsonism clinics experienced hypersexuality as a consequence of anti-parkinsonian therapy. The cases include only those whose sexual behavior on treatment became a concern to the patient's family or a social agency. The majority of patients were men and had a relatively early onset of parkinsonian symptomatology. There was no relation between functional improvement and increased sexuality. Most patients showed some element of dose dependency between antiparkinsonian drugs and the hypersexual behavior. Prior sexual profile included from no sexual outlet to hypersexuality. Neither the prior history of psychiatric illness nor brain damage predisposed to such response on treatment, and in most patients, it was not a part of hypomania or a more diffuse psychiatric disturbance. We propose that hypersexuality on antiparkinsonian drugs is consequent to inhibition of prolactin secretion. PMID- 2575450 TI - Effects of terguride in patients with Huntington's disease. AB - trans-Dihydrolisuride, a partial dopamine receptor agonist, was tested for its effects on chorea in a double-blind, crossover clinical study in 10 patients with Huntington's disease. In eight patients, a neurophysiological evaluation was also performed. No reduction in choreic movements or improvement in voluntary movement performance was observed. However, in some patients, there was a slight improvement in patients' alertness and a reduction of the movement reaction time. PMID- 2575452 TI - Synthesis of N-beta-D-glucopyranosyl derivatives of barbital, phenobarbital, metharbital, and mephobarbital. AB - The condensation of per(trimethyl)silylbarbital and -phenobarbital with 1,2,3,4,6 penta-O-acetyl-beta-D-glucopyranose in the presence of stannic chloride in dichloroethane gave moderate yields of the beta-coupled barbiturate N-D glucopyranosyl derivatives. Reaction of metharbital and mephobarbital under the same conditions was unsuccessful. The homologous N-methylglucosides were prepared by reaction of the barbital and phenobarbital N-glucosyl derivatives with diazomethane. The diastereomers of the phenobarbital and mephobarbital derivatives were resolved by use of C-18 reverse-phase h.p.l.c. 1H- and 13C n.m.r. spectroscopy, and thermospray 1.c.-m.s. proved to be the most useful methods for characterizing the barbiturate glucosides. PMID- 2575451 TI - Posterior fossa subdural empyema in the term neonate. AB - A case of posterior fossa subdural empyema following neonatal meningitis is reported. Computerized tomography (CT) carried out on the 11th day after birth showed an obstructive hydrocephalus with diffuse cerebellar swelling. Ventricular drainage was carried out to control the hydrocephalus and antibiotics were given intravenously. A second CT scan taken on the 21st day after birth revealed a loculated subdural empyema in the retrocerebellar space. Serial CT scans showed a diminution in the size of the empyema. PMID- 2575453 TI - A comparison of the efficacy and tolerability of diflunisal and dextropropoxyphene napsylate with acetaminophen in the management of mild to moderate pain after arthroscopy of the knee. AB - We conducted an open-label randomized clinical trial comparing the efficacy and tolerability of diflunisal and dextropropoxyphene napsylate with acetaminophen (DPN-A) in the management of mild to moderate pain following arthroscopic surgery of the knee. Patients used a self-rating pain scale to evaluate the analgesia provided by each medication. Twenty-six patients completed the study; 12 received diflunisal and 14 received DPN-A. The physicians found no significant differences between the two groups in their preoperative or postoperative assessment of pain, tenderness, swelling, and active range of motion. There were no statistically significant differences between the two groups' mean pain scores or assessment of the overall efficacy of their respective drugs. No patient in either treatment group reported any adverse effects. PMID- 2575454 TI - Ultracytochemical localization of guanylate cyclase in early human placenta. AB - Previous biochemical and cytochemical studies have indicated that in human term placenta the enzyme guanylate cyclase (GC) is associated mostly with the cytosolic fraction of homogenates and localized on the syncytiotrophoblast microvillous border. In the present study we have shown cytochemically the GC particulate form in early human placenta using guanylyl-imidodiphosphate [Gpp(NH)p] as substrate and NaN3 as activator. In samples of placental villi taken from the 6th to 12th week of pregnancy, the GC reaction product was always found on the apposing Langhans cytotrophoblast and syncytiotrophoblast plasma membranes. Furthermore, GC was present on cells in mitosis of the Langhans cytotrophoblast. From the 11th week GC was also visible on basal plasma membranes of Langhans cytotrophoblast and on endothelial cells of fetal capillaries. In samples of human term placenta GC was detectable on the syncytiotrophoblast microvillous border. This suggests a shift of enzyme localization during pregnancy. PMID- 2575455 TI - The human tyrosine hydroxylase gene. AB - 1. Tyrosine hydroxylase (TH) is a rate-limiting enzyme for catecholamine biosynthesis, and it is a pterin-requiring monooxygenase. Both cDNAs and genomic DNA of human TH have been cloned and the nucleotide sequence has been determined. 2. Four similar but distinct mRNAs encode human TH. The results of Southern blot analysis and the nucleotide sequence of the human TH genomic DAN indicate that the four types of human TH mRNA are produced through alternative splicing from a single gene. 3. The human TH gene was split into 4 exons and 13 introns. The 12 bp insertion sequence is encoded by the 3'-terminal portion of the first exon. The 81-bp insertion sequence corresponds to the second exon. Two kinds of alternative splicing are involved: the alternative use of two donor sites in the first exon and the inclusion/exclusion of the second exon. 4. The four types (type 1-4) were expressed in COS cells, and all had enzymatic activities. The type 1 enzyme had the highest homospecific activity (activity per enzyme protein), the values for the other enzymes ranging from 30 to 40%. The Km values of the four types for L-tyrosine and 6-methyl-5,6,7,8-tetrahydropterin were similar. PMID- 2575456 TI - Cyclin/PCNA immunostaining as an alternative to tritiated thymidine pulse labelling for marking S phase cells in paraffin sections from animal and human tissues. AB - Paraffin sections from animal or human tissues fixed in different fixatives were submitted to immunostaining with the mouse monoclonal antibody 19A2, developed by Ogata et al. (1987a) against cyclin/PCNA. Detection of the bound antibody was performed by the indirect method with biotinylated sheep antibody and streptavidin-biotin-peroxidase complexes. No, or faint, nuclear staining was seen in material fixed in ethanol, Bouin, Bouin-Hollande, Carnoy or formaldehyde, whereas readily detectable immunocytochemical reaction was constantly observed over nuclei of methanol-fixed tissues. Hydrolysis with 2 N HCl prior to immunocytochemistry (as currently performed to render incorporated BrdU accessible to antibodies) somewhat improved the results with Bouin or Carnoy and markedly augmented the intensity of the peroxidase reactions in formaldehyde and in methanol-fixed tissues. The distribution of the positive nuclei in the two latter cases coincided with the proliferative compartment. On the other hand, double labelling with [3H]-thymidine and with the cyclin/PCNA antibody revealed that in methanol-fixed tissues the cyclin/PCNA labelling index did not differ by more than 6% from the [3H]-thymidine index. Besides the two labels overlapped in a proportion of labelled cells that was in reasonable agreement with expectation considering cells flow in and out of S phase since the time of [3H]-thymidine injection. This indicates that both labels recognize the same cells in this material. In contrast, in formaldehyde-fixed tissues, the cyclin/PCNA labelling index markedly exceeded the [3H]-thymidine labelling index. From this it is concluded that cyclin/PCNA immunostaining can be used: (1) In formaldehyde-fixed tissues (including existing material stored as paraffin blocks): for defining and mapping the proliferative (or germinative) compartment. (2) In methanol-fixed tissues as a substitute to the [3H]-thymidine autoradiographic labelling index. From this, a method is proposed (derived from classical 'double-labelling' technique) for measuring S phase duration in tissues fixed at a known interval time after a single labelling with [3H]-thymidine (or BrdU) and submitted to cyclin/PCNA immunocytochemical detection and to autoradiography (or to BrdU immunostaining). PMID- 2575457 TI - Are adrenergic neurons subject to a serotoninergic influence in the nucleus tractus solitarii? A morphological and biochemical study in the rat. AB - The possible relationships between adrenaline-synthesizing neurons and serotoninergic afferent fibers in the nucleus tractus solitarii of the rat were investigated both morphologically and biochemically. Adrenergic elements (cell bodies, dendrites and nerve endings) were detected simultaneously with serotoninergic axonal varicosities in the same electron-microscopic sections by means of combined phenylethanolamine-N-methyltransferase immunocytochemistry and [3H]serotonin-uptake radioautography. Among some 500 serotoninergic varicosities scanned in the areas of significant overlap between the 2 types of labeling, only 3 were directly apposed to an adrenergic process, identified as a dendrite in each case. No synaptic membrane differentiations were seen at these occasional sites of contact. Destruction of the serotonin input by 5,7-dihydroxytryptamine had no significant effect on the tyrosine hydroxylase dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase enzymatic activities in the C2 adrenergic region, but induced 22% and 38% increases of tyrosine hydroxylase and dopamine-beta-hydroxylase activities, respectively, in the neighboring A2 noradrenergic area. Taken together, these results suggest that serotoninergic and adrenergic neurons do not significantly interact in the nucleus tractus solitarii; this implies that the possible catecholaminergic relays for the action of serotonin in autonomic regulation at this level could consist of noradrenergic neurons rather than of their adrenergic counterparts. PMID- 2575458 TI - Intracellular calcium and hormone secretion in clonal AtT-20/D16-16 anterior pituitary cells. AB - Intracellular ionized Ca2+ concentration was measured in clonal mouse anterior pituitary tumor cells with the fluorescent Ca2+ indicator Quin-2. In control physiological solution, free cytoplasmic Ca2+ concentration was found to be 139 +/- 11 nM. Replacement of 50 mM NaCl by 50 mM KCl in the extracellular fluid caused a 29 mV depolarization and a 4.2-fold increase in the concentration of free cytoplasmic Ca2+. Under comparable depolarizing conditions, a specific influx of 2.66 nmole of 45Ca2+ per mg protein was detected 1 min after addition of high K+, accompanied by a marked increase in the initial rate of beta endorphin secretion. In the absence of external Ca2+, depolarization by K+ produced little or no increase in either intracellular free Ca2+ or hormone release. Incubation of AtT-20/D16-16 cells in the secretagogue norepinephrine led to a depolarization accompanied by an increase in spontaneous action potential frequency and a marked elevation in cytosolic Ca2+ concentration. Exposure of cells to somatostatin, an inhibitor of hormone release, led to only transient decreases in burst frequency and no significant reduction in intracellular Ca2+ levels. These results indicate that in addition to intracellular Ca2+, other factors also control secretory activity in AtT-20/D16-16 anterior pituitary cells. PMID- 2575459 TI - Existence of two calcium currents recorded at normal calcium concentrations in single frog atrial cells. AB - A low threshold calcium current (ICALT) was found in Cs+-loaded frog atrial cells in addition to the classical (high threshold) calcium current (ICaHT), and was investigated at physiological Ca2+ concentrations using the whole-cell patch clamp technique. The threshold potentials were approximately -60 mV for ICaLT and -40 mV for ICaHT. The amplitude and time course of ICaLT were almost unaffected by exchanging Ca2+ for Ba2+ or Sr2+, while those of ICaLT were modified. ICaLT was inhibited by Ni2+ (40 x 10(-6) M) but was not affected by Cd2+ (20 x 10(-6) M) while ICaHT was inhibited by Cd2+ and only slightly reduced by Ni2+ at the same concentrations. Co2+ (10(-3) M) inhibited both types of calcium currents while La3+ (5 x 10(-6) M) had a greater blocking effect on ICaHT. ICaLT was neither modified by dihydropyridines (nisoldipine, Bay K) nor by adrenergic agonists (adrenaline, noradrenaline, isoprenaline), in contrast with the effects of these agents on ICaHT. Angiotensin II (40 x 10(-9) M) increased and atrial natriuretic factor (0.1 x 10(-6) M) decreased ICaLT while ICaHT, was not modified by these two substances. PMID- 2575460 TI - Solution syntheses of two enkephalin-containing peptides, peptide E and dynorphin(1-24), using Nin-(2,4,6-triisopropylphenylsulfonyl)tryptophan. AB - Two enkephalin-containing peptides, peptide E and dynorphin(1-24), were synthesized by conventional solution methods employing a new Trp derivative, Nin (2,4,6-triisopropylphenylsulfonyl)tryptophan [Trp(Tps)]. All protecting groups employed including the Tps group were removed by treatment with 1 M trifluoromethanesulfonic acid (TFMSA)-thioanisole in trifluoroacetic acid (TFA) at the final steps of these syntheses. Subsequent purifications by Sephadex G-25 chromatography, CM-Biogel A ion exchange chromatography, and reversed-phase high performance liquid chromatography afforded highly purified samples. Both synthetic peptide E and dynorphin(1-24) exhibited high in vitro opioid activity. The usefulness of this new tryptophan derivative for practical peptide synthesis was established through these syntheses of complex Trp-containing peptides. PMID- 2575462 TI - Bioisosteric transformation of H1-antihistaminic benzimidazole derivatives. AB - With the aim of obtaining new H1-antihistaminic agents, transformations of previously reported antihistaminic benzimidazoles were performed on the basis of the concept of bioisosterism. Among the compounds prepared, imidazo[4,5 b]pyridine (8) and 4(3H)-quinazolinone (11) exhibited significant H1 antihistaminic activity. PMID- 2575461 TI - Synthesis and pharmacological evaluation of procaterol derivatives having a tert amino group. AB - A series of procaterol derivatives having a tert-amino group was synthesized. Among them, a morpholino derivative (4a, R1 = H, NR2R3 = morpholino) showed beta selective and rather potent adrenoceptor stimulant activities in an in vivo assay using anesthetized dogs. On the other hand, a morpholinopropanol analogue (4j, R1 = CH3, NR2R3 = morpholino) showed 400 times less potent bronchodilator activity than that of 4a. Some of the compounds showed weak bronchodilator activities and weak effects on the heart. It seems that steric hindrance around the nitrogen atom of catecholamines has a significant influence on beta-adrenoceptor stimulant activities. Compound 4a also showed anti-allergic action estimated in terms of the inhibition of homologous passive cutaneous anaphylaxis in rats. PMID- 2575463 TI - A nitrocellulose membrane-based ELISA for the detection of Plasmodium infections in mosquitos. AB - A nitrocellulose (NC) membrane was evaluated as a solid-phase support for the detection of malaria-infected mosquitos using monoclonal antibodies (MAb) with a laboratory model based on Plasmodium inui and Anopheles dirus. MAbs produced against sporozoites of the N34 strain of P. inui, and selected by immunofluorescence assay and the circumsporozoite precipitin test, were used. A one-site indirect NC-ELISA that used unlabelled MAb and enzyme-labelled anti mouse IgG was developed. Its sensitivity was about 200 sporozoites and it reliably detected one infected mosquito in a pool of 20. This indirect NC-ELISA has the advantage that it does not require direct conjugation of the MAb to an enzyme or biotin. In the direct one-site NC-ELISA, which is also reported, the relatively simple biotinylation procedure was an alternative to the enzyme- or radiolabelled MAbs. The NC-ELISAs were simple and rapid. Furthermore, the indirect NC-ELISA can be used to detect sporozoite antigen localized in various body sectors of mosquitos. PMID- 2575465 TI - Effect of ischaemia on the activities of human hepatic acyl-CoA:cholesterol acyltransferase and other microsomal enzymes. AB - The effect of ex vivo ischaemia at 37 degrees C on the activities of human hepatic acyl-CoA:cholesterol acyltransferase (ACAT), acyl-CoA hydrolase and carboxylesterase and on the microsomal cholesterol and total phospholipid concentrations was determined in liver tissue from two patients. ACAT activity decreased exponentially with ischaemia, corresponding to half-lives of 59 and 54 min in the two samples. Acyl-CoA hydrolase activity of microsomes was not affected by ischaemia, whereas carboxylesterase activity of microsomes decreased with a corresponding increase in cytosolic carboxylesterase activity. No changes in microsomal cholesterol and total phospholipid concentrations corresponding to the changes in ACAT or carboxylesterase activity were observed. ACAT activity was also determined in microsomes prepared from twenty human liver samples obtained at surgery with in vivo warm ischaemia times ranging from 5-120 min. The data obtained agree well with the ex vivo results, showing a half-life of 57 min for the loss of ACAT activity. Therefore, in comparing ACAT activities in liver samples with different ischaemia times, an appropriate correction must be made for warm ischaemia time. PMID- 2575464 TI - Selective retardation of the development of the basal forebrain cholinergic and pontine catecholaminergic nuclei in the brain of trisomy 16 mouse, an animal model of Down's syndrome. AB - Brain development, examined at embryonic day 17, was retarded in murine trisomy 16 (Ts16). Ts16 is considered to serve as a model of the human trisomy 21 (Down's syndrome) by virtue of the presence in the mouse chromosome 16 of a set of genes located in humans in the segment of chromosome 21 that is requisite to produce the phenotypic features of Down's syndrome when present in triplicate. In addition to a reduction in brain size and cortical thickness, we observed a severe reduction throughout the brain in the density of muscarinic receptors, assessed by autoradiographic detection of specifically bound tritiated N-methyl scopolamine, and by the failure of the development of the differentiated pattern of receptor distribution in the brainstem. The effect of gene dosage was also examined on specific neuronal populations. The distribution of acetylcholine esterase (AChE)-, tyrosine hydroxylase (TH)- and 5-hydroxytryptamine (5-HT) positive cells in the trisomic brain was similar to that observed in chromosomally balanced littermates. On the other hand, the number of AChE positive cells was 60-70% of the estimates in littermate controls in regions containing the septum, the vertical and horizontal limbs of the diagonal band and the basal forebrain cholinergic nuclei. Similarly, the number of TH-positive cells was reduced by about 30% in the pons. In contrast, in the trisomic foetuses the number of TH-positive cells in the mesencephalon and the diencephalon was similar to that in littermate controls, while that of 5-HT-positive cells in the mesencephalic nuclei was only slightly affected, if at all. Ts16 results, therefore, in a selective retardation of some neuronal systems, and this may lead to a perturbation of brain development. Furthermore, the systems whose development was retarded selectively are those which in Down's syndrome adults exhibit pronounced deficits of cells that--in case the murine Ts16 is a valid model--may also involve developmental disorders. PMID- 2575466 TI - Assay of methylmalonyl CoA mutase with high-performance liquid chromatography. AB - An assay for methylmalonyl CoA mutase activity is described. Succinyl CoA produced in this method is separated from the substrate, methylmalonyl CoA, by reverse-phase high-performance liquid chromatography and is quantified. This method is useful to differentiate mutase apoenzyme deficiency (mut0, mut-) and the defect in deoxyadenosylcobalamin synthesis using fibroblasts cultured in high concentration of supplementary hydroxocobalamin. In methylmalonic acidemia, measurement of lymphocytes mutase activity offers therapeutical and prognostic informations. PMID- 2575467 TI - A lack of coordination in the release of urinary lysosomal and brush border enzymes following renovascular surgery. AB - The urinary secretion of two lysosomal enzymes, N-acetyl-D-glucosaminidase (NAG, EC 3.2.1.30) and beta-glucuronidase (GLR, EC 3.2.1.31), and two brush border enzymes, alanine aminopeptidase (AAP, EC 3.4.11.2) and gamma-glutamyltransferase (GGT, EC 2.3.2.2), was examined in apparently healthy individuals and in patients before and after renovascular surgery for treatment of hypertension. Eight out of nine patients had elevated levels of at least one enzyme before surgery. The ranking in their frequency of elevation was NAG greater than AAP greater than GLR greater than GGT. In comparing the release of any two enzymes in apparently healthy individuals, the release was coordinated except for GGT and GLR. In individual patients following surgery the excretion of the lysosomal enzymes was highly coordinated whereas the release of the brush border enzymes was less coordinated. Comparisons of lysosomal to brush border enzyme activities revealed dissimilar release patterns between these two classes of enzymes. Analysis of variance over the entire hospitalization period showed that NAG/GLR (p = 0.42) and AAP/GGT (p = 0.12) did not vary significantly whereas all comparisons of lysosomal to brush border enzymes varied significantly (p less than or equal to 0.03). These results indicate that enzymes derived from different subcellular organelles, lysosomes or brush borders, have similar release patterns. However, the lack of a significant correlation between lysosomal and brush border enzyme excretion implies that the two processes are not interdependent. These studies further suggest that the transient pathophysiological changes that occur within renal cells following renovascular surgery affect these cellular components in different ways. PMID- 2575468 TI - Simultaneous assay of thyroid adenylate cyclase- and growth-stimulating antibodies using FRTL-5 cells. Evidence suggesting their identity in patients with Graves' disease. AB - The relationship between thyroid growth-stimulating antibodies (TGSAb) and thyroid adenylate cyclase-stimulating antibodies (TSAb) in patients with Graves' disease is still a matter of controversy. To investigate this problem, we have developed an assay for the simultaneous measurement of TSAb and TGSAb using FRTL 5 cells. TSAb was detected by its ability to stimulate iodide (I-) uptake and TGSAb by the 3H-thymidine ([3H]-Tdr) incorporation assay. Thirty-four immunoglobulin G (IgG) preparations from patients with active Graves' disease were selected from a previous series in order to include both TSAb-negative IgGs (n = 9) and TSAb-positive IgGs (n = 25) by the cAMP stimulation assay, with a wide range of stimulatory activity. With one exception, the TSAb-positive IgGs produced a significant stimulation of I- uptake; 20 of them were also TGSAb positive. The nine IgGs negative in the cAMP assay, were also negative in the I uptake and the [3H]-Tdr incorporation assays. The majority of samples had a similar potency in the two assays and a significant positive correlation was found (r = 0.76; P less than 0.001). Two IgGs previously shown to inhibit TSH stimulated adenylate cyclase in FRTL-5 cells produced an almost complete inhibition (80-90%) of both TSH- and Graves' IgG-stimulated I- uptake and [3H] Tdr incorporation. In conclusion, using a simultaneous assay for thyroid growth and adenylate cyclase stimulation, TGSAb in Graves' patients were found only in TSAb-positive IgGs; both Graves' IgG-stimulated activities were inhibited by antibodies blocking the TSH-dependent adenylate cyclase stimulation. Our data strongly suggest that the same antibody may be responsible for both goitre and thyroid hyperfunction of Graves' disease. PMID- 2575469 TI - Diuretics and other antihypertensive drugs and glycemic control in non-insulin dependent diabetics with hypertension. A survey by the Fukuoka Diabetes Clinic Group. AB - We compared the levels of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1) in non-insulin-dependent diabetics with hypertension who were treated with monotherapy of diuretics or other antihypertensive drugs (AHD) and in those who were not given any AHD. Total 162 patients were divided into the four groups; the control group without AHD (n = 45), the diuretics group (n = 42), the beta-blocker group (n = 30) and the Ca-antagonist group (n = 45). FPG and HbA1 levels were 153 +/- 44 mg/dl and 10.0 +/- 2.3% for the control group, 145 +/- 55 mg/dl and 9.8 +/- 2.2% for the diuretics, 165 +/- 63 mg/dl and 10.2 +/ 2.1% for the beta-blocker and 158 +/- 42 mg/dl and 10.4 +/- 2.0% for the Ca antagonist, respectively. There were no significant differences in the levels of FPG and HbA1 among the four groups. Multivariate analysis also revealed no difference in glycemic control even when anti-diabetic treatment (diet alone, oral hypoglycemic agents or insulin), body mass index, serum potassium, systolic and diastolic blood pressures and age were taken into account. Blood pressure levels did not differ among the groups except control and they were well controlled at the low doses of AHD. Our results suggest that the choice of low dose diuretics for the treatment of hypertension in non-insulin-dependent diabetics might not be necessarily excluded by the only reason of the possible deleterious influence on glycemic control. PMID- 2575470 TI - Interleukin-4 suppresses immunoglobulin production by peripheral blood lymphocytes of patients with common variable immunodeficiency (CVI) induced by supernatants of T cell clones. AB - Supernatants of both CD4+ and CD8+ alloreactive T cell clones induced IgM, IgG and IgA synthesis by peripheral blood lymphocytes (PBL) of healthy donors in vitro. These supernatants were also tested on their capacity to induce immunoglobulin production by PBL of four patients with CVI and one patient with CVI and thymoma. A low degree of IgM, IgG and IgA production was induced in one patient with CVI. In the patient with CVI and thymoma, induction of IgG and IgA synthesis was in the normal range, whereas IgM production was reduced. In the three other patients only a low production of IgM was induced. Interestingly, pre incubation of the PBL for 24 h with interleukin-4 (IL-4) suppressed immunoglobulin production both by PBL of the patients with CVI and healthy donors. The strongest inhibitory effects were observed on IgA synthesis. These data indicate that B cells of three patients with CVI can not be induced to switch to IgG or IgA producing cells in vitro. In contrast, B cells of the patient with CVI and thymoma were able to respond to the relevant B cell growth and differentiation factors present in the T cell clone supernatants, suggesting that the T cells of this patient may fail to produce these factors. However, the proliferative responses of the T cells to phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM), were normal in all five patients tested. In addition, the interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production by PBL of the five patients was also in the normal range. Although only a small number of patients was tested, these results support the view that defects in both regulatory T cell functions and/or intrinsic B cell defects may contribute to the pathogenesis of CVI. PMID- 2575471 TI - CR1 polymorphism in hydralazine-induced systemic lupus erythematosus: DNA restriction fragment length polymorphism. AB - The contribution of genetic factors in the reduction in erythrocyte CR1 levels observed in hydralazine (Hz) induced systemic lupus erythematosus (SLE) was investigated by determining the frequency of a HindIII restriction fragment length polymorphism (RFLP) in the CR1 gene. This RFLP is associated with quantitative erythrocyte CR1 expression. Individuals who have developed SLE as a reaction to Hz therapy, consanguinous relatives of the Hz-SLE patients, controls who had been treated with Hz without any adverse reaction, and the consanguinous relatives of these controls were included in this study. No difference was found in the frequency of occurrence of the alleles associated with CR1 expression between the Hz-SLE patients and the control groups (P greater than 0.2). Individuals from the Hz-SLE group who were homozygous for the 7.4 kb 'high expressor' allele had lower mean levels of erythrocytes CR1 (564 +/- 65) than the corresponding homozygous subgroups within the Hz-SLE relative group (774 +/- 46), the Hz control group (756 +/- 80) and the Hz control relatives group (825 +/- 66). In addition, 50% of the Hz-SLE patients in the 'high expressor' subgroup who had less than 500 CR1 per erythrocyte had elevated levels of circulating immune complexes. This study suggests that individuals who are genetically low expressors of erythrocyte CR1 are not predisposed to developing SLE in response to Hz therapy, and that in a subgroup of genetically 'high expressors', low CR1 levels are associated with elevated levels of circulatory immune complexes. PMID- 2575472 TI - Increase of IgA-specific switch T cells in patients with IgA nephropathy. AB - Enumeration and functional analysis of CD4+ T cells with receptors for the Fc portion of IgA (i.e. T alpha 4 cells) in the peripheral blood of patients with IgA nephropathy, their relatives and age-matched controls were performed to elucidate polyclonal activation of IgA production in this disease. Enumeration of T alpha 4 cells was performed by a fluorescence activated cell sorter, and functional analysis was carried out by separation of T alpha 4 cells, and IgM-, IgA- and IgG-bearing lymphocytes using panning methods followed by cultures of these cells for 7 days with pokeweed mitogen. There was a significant increase in the amount of peripheral blood T alpha 4 cells in patients with IgA nephropathy and their relatives. T alpha 4 cells specifically enhanced the switch of IgM bearing cells to IgA-bearing cells, and this switch activity was inhibited by addition of human myeloma IgA. It is suggested that T alpha 4 cells may be responsible for polyclonal activation of IgA production in IgA nephropathy. PMID- 2575474 TI - Cardiovascular effects of rilmenidine, a new alpha 2-adrenoceptor agonist, and clonidine in conscious spontaneously hypertensive rats. AB - 1. The acute and chronic effects of rilmenidine, a partial agonist of alpha 1- and alpha 2-adrenoceptors with antihypertensive properties, were compared to those of clonidine on blood pressure (BP), heart rate (HR) and the urinary excretion of catecholamines, which was used as an index of sympathetic activity. 2. As these drugs are known to interfere centrally and peripherally with the sympathetic nervous system, long-term arterial blood pressure recordings in freely moving unstressed adult spontaneously hypertensive rats (SHR) were used. 3. Acute i.v. administrations of rilmenidine (0.3 mg/kg at 1200 h, 1.2 mg/kg at 1700 and 2200 h) and clonidine (12 micrograms/kg at 1200 h, 50 micrograms/kg at 1700 and 2200 h) induced short-lasting increases in BP associated with a decrease in HR, which were followed by prolonged, dose-dependent decreases in BP without bradycardia. The pressor effect was less marked and the associated bradycardia was more marked in active SHR with physiologically high sympathetic activity than in resting SHR. 4. A 12-day oral treatment with rilmenidine (6.0 mg/kg daily) or clonidine (150 micrograms/kg daily) induced moderate decreases in BP without change in HR. Rilmenidine but not clonidine decreased normetanephrine (NMN) excretion in active but not in resting SHR. 5. Finally, during the 24 h following the cessation of the treatments, BP returned to normal, without significantly exceeding that of untreated controls. However, upswings in BP or HR were observed, more markedly and frequently after clonidine than after rilmenidine. 6. In conclusion the effects of alpha 2-adrenoceptor agonists appear to be influenced by the pre-existing sympathetic tone. The general agreement between these data and those observed in patients demonstrates that the use of conscious unstressed animals is of value to determine the cardiovascular effects of drugs which act on the sympathetic nervous system. PMID- 2575475 TI - Effects of adenosine antagonism and beta-blockade during low-flow ischaemia in rat heart. AB - 1. The effects of adenosine antagonism (8-phenyltheophylline) and beta-blockade (1-propranolol) were examined during low-flow ischaemia (0.5 mL/min per g for 20 min) in rat heart. 2. Myocardial adenosine release, heart rate, and left ventricular developed pressure were monitored to determine whether endogenous adenosine affected ischaemic function directly, and/or via interaction with endogenous catecholamines. 3. Adenosine release increased more than 10-fold during low-flow ischaemia. Release displayed a phasic pattern, with maximal release occurring at 10 min. Ischaemia produced bradycardia (-180 beats/min) which was reduced by 8-phenyltheophylline infusion (P less than 0.001, n = 10). Adenosine antagonism also significantly increased left ventricular developed pressure in the initial 5 min of ischaemia (P less than 0.001, n = 10). 4. beta blockade alone was without effect in ischaemic hearts, however, beta-blockade significantly reduced the initial increases in heart rate and developed pressure observed during infusion of 8-phenyltheophylline (P less than 0.001, n = 10). The effect of beta-blockade was transient, occurring in the initial 5-6 min of ischaemia. 5. The data indicate that endogenous adenosine directly mediates greater than 30% of the bradycardia associated with low-flow ischaemia, and that endogenous adenosine inhibits the release and/or the effects of endogenous catecholamines produced during the initial 5-6 min of ischaemia. PMID- 2575473 TI - T cell-dependent chronic neutrophilia during mycobacterial infections. AB - Euthymic (nu/+) C57BL/6 mice intraperitoneally inoculated with 2.5 x 10(6) colony forming units (CFU) of Mycobacterium avium developed a chronic peritoneal neutrophilic granulocytosis during the 30 days of infection studied; in contrast, congenitally athymic nude (nu/nu) mice of C57BL/6 background did not show such persistent neutrophil influx. The acute phase of peritoneal infection, characterized by an extensive accumulation of neutrophils peaking at 6 to 12 h post-inoculation, was similar in euthymic and athymic mice. Subcutaneous vaccination of C57BL/6 mice with BCG enhanced the peritoneal influx of granulocytes after the i.p. inoculation of 2.5 x 10(60 CFU of M. avium. Finally, spleen cells from M. avium-infected mice pulsed in vitro with mycobacterial antigen induced a higher neutrophil accumulation after inoculation into the peritoneal cavity of naive recipient mice than unpulsed spleen cells or spleen cells from noninfected mice. These data indicate that the immune system is involved in the regulation of the chronic neutrophil influx during mycobacterial infection. PMID- 2575476 TI - Histamine enhances hypoxia-induced ventricular arrhythmias in isolated rat hearts. AB - 1. The effects of hypoxia, histamine-receptor agonist perfusion, and their combination on cardiac rhythm were studied in isolated rat hearts. 2. While hypoxia induced a high incidence of ventricular tachycardia or fibrillation, only a few preparations developed ventricular arrhythmias in response to perfusion with high concentration of histamine, 2-pyridylethylamine or impromidine. 3. The times of onset of hypoxia-induced ventricular arrhythmias were significantly shortened by perfusion with either histamine, 2-pyridylethylamine or impromidine. The accelerated occurrence of hypoxia-induced ventricular arrhythmias by histamine was significantly abolished by pretreatment with either diphenhydramine or cimetidine. 4. The results indicate that hypoxia and histamine can increase ventricular vulnerability of the rat heart to each other. It is also suggested that the arrhythmogenic actions of histamine in hypoxic rat hearts are mediated by both histamine H1-and H2-receptors. PMID- 2575477 TI - Sulphasalazine and ankylosing spondylitis: an open pilot study. PMID- 2575478 TI - Transglutaminase-dependent lymphocyte transformation in type 2 diabetes mellitus. AB - The transglutaminase involvement in phytohaemagglutinin (PHA) stimulated lymphocyte transformation (measured as (3H)thymidine incorporation) was studied in lymphocytes from 20 patients with type 2 diabetes mellitus and 20 healthy controls by including in the system the specific transglutaminase pseudosubstrate monodansylthiacadaverine (MDTC). In the presence of MDTC, (3H)thymidine incorporation was significantly and concentration-dependently reduced in both groups but more pronouncedly in the diabetes patients. The MDTC concentration needed to give a 50% reduction of the PHA-stimulated (3H)thymidine incorporation was significantly lower in lymphocytes from diabetic patients than in those from controls (p less than 0.02). The data suggest impaired lymphocyte transglutaminase function in type 2 diabetes mellitus. PMID- 2575479 TI - [Evaluation of the efficacy of the magnesium salt of N-acetyl-aspartyl-glutamic acid in the treatment of acute rhinitis]. AB - The object of the above study was to evaluate the tolerability and possible therapeutic use of MgNAAGA (Mg salt of N-acetyl-aspartyl-glutamic acid) in patients with allergic rhinitis. Out of 22 subjects with respiratory allergy, 12 were treated for 15 days with MgNAAGA and 10 with DSCG for the same length of time. During this period, patients kept a diary in which they recorded the following symptoms: rhinorrhea, itching, sneezing and nasal obstruction. The trial drug was found to be well tolerated and not to give rise to relevant side effects. The therapeutic efficacy was similar to that of DSCG. PMID- 2575480 TI - Bopindolol in the treatment of hypertension: a double blind study comparing bopindolol and metoprolol. AB - The article presents the experience gained with a new betablocker- bopindolol-in the treatment of hypertension. Using a three-month double blind study conducted in 2 centres, the antihypertensive effect of bopindolol and metoprolol was compared in a total of 86 patients. The incidence of undesirable effects was determined, and biochemical parameters before and after therapy were followed up. Both drugs were equally effective in controlling blood pressure. In 70% of patients with mild and moderate hypertension, diastolic pressure values less than 95 mmHg were obtained in monotherapy with a betablocker. The incidence of undesirable effects was low, the drug was tolerated well. Biochemical parameters did not change within the three months of study. PMID- 2575481 TI - Cultured human retinal pigment epithelial cells express basic fibroblast growth factor and its receptor. AB - Basic fibroblast growth factor (bFGF) has been implicated in the maintenance of neuronal differentiation, the induction of neovascularization and intravitreal proliferative diseases. We have found that human retinal pigment epithelial (RPE) cells grown in vitro transcribe the bFGF gene and synthesize a peptide that crossreacts with anti-bFGF antibodies. In culture, these cells appear to release activity with biological and biochemical properties similar to bFGF. RPE cells have specific bFGF receptors and proliferate in response to bFGF. Thus, it is possible that the RPE cell is an important source of retinal bFGF and may respond to bFGF in an autocrine manner. PMID- 2575482 TI - Localization of gamma glutamyl transpeptidase in bovine retina. AB - Gamma-glutamyl transpeptidase (GGTP) is a membrane bound enzyme which has an important role in regulation of glutathione and glutamate in the retina. We have used histochemical and colorimetric enzyme assays to localize GGTP in the bovine retina and choroid. Our results demonstrate that (i) GGTP is present in retinal microvessels but not choroidal microvessels. (ii) Retinal microvascular endothelium loses the ability to express GGTP in cultured cells. (iii) GGTP is present in Muller cells. (iv) Isolated and purified rod outer segments contain high levels of GGTP. (v) Retinal pigment epithelial cells (RPE) in vivo and in culture contain GGTP. The findings of this study lend support to the concept that GGTP may be a biochemical marker for cellular systems which are part of specialized diffusion barriers. PMID- 2575483 TI - Autosomal dominant aniridia linked to the chromosome 11p13 markers catalase and D11S151 in a large Dutch family. AB - In a large pedigree with autosomal dominant aniridia, we found close linkage between the aniridia locus AN2 and the markers catalase (CAT) (zeta = 7.27 at theta = 0.00) and D11S151 (zeta = 3.86 at theta = 0.10) flanking the AN2 locus on 11p13. Positive lod scores were also obtained for the 11p13----11p14 markers D11S16 and FSHB with the linkage group CAT/AN2/D11S151. We conclude that the autosomal dominant aniridia in this family is due to a mutation at the AN2 locus on 11p13. We have excluded linkage (zeta less than -2 at theta less than 0.18) between the aniridia and the chromosome 2p25 marker D2S1 (linked to ACP1). PMID- 2575484 TI - Localization of two alkaline phosphatase genes to the proximal region of mouse chromosome 1. AB - Using a human cDNA clone encoding the intestinal form of alkaline phosphatase, we have identified and mapped by RFLP analysis in a Mus spretus x C57BL/6J interspecies backcross two alkaline phosphatase genes which segregate independently on the proximal part of mouse Chromosome 1. The gene order and intergene distances were determined by standard backcross analysis as: centromere Len-2 - 19.0 cM - Akp-3 - 20.0 cM - Akp-4 - 2.0 cM - Ren-1. PMID- 2575485 TI - Chromosomal localization to 3q21----qter and two TaqI RFLPs of the human prostate specific acid phosphatase gene (ACPP). AB - The chromosomal location of the gene encoding human prostate-specific acid phosphatase (ACPP) was determined by Southern blotting analysis of panels of human x rodent (mouse or Chinese hamster) somatic cell hybrids, using the PAP 1007 and PAP-1004EP ACPP cDNA probes. The ACPP gene was assigned to chromosome 3, which was confirmed by screening a chromosome 3-specific genomic library. Sublocalization of this gene was carried out using hybrids that had retained only various portions of human chromosome 3. The ACPP gene was found to segregate specifically with the chromosomal segment 3q21----qter. Analysis of Southern blots of TaqI-digested DNAs from unrelated individuals and members of large families from northern Finland revealed two simultaneous diallelic restriction fragment length polymorphisms (RFLPs), A and B, when using either PAP-1004EP or PAP-1006A ACPP cDNA probes, but not the 5' flanking PAP-1007 probe. Allele frequencies for polymorphism A were .09 (A1) and .91 (A2), and for polymorphism B, .38 (B1) and .62 (B2). There appears to be only a very minor linkage disequilibrium (chi 2 = 1.12, 0.35 greater than P greater than 0.25) between the two TaqI RFLPs at the ACPP locus. For reasons presently unknown, homozygotes for polymorphism B appear to be overrepresented. These polymorphisms could be of importance in characterizing human prostate cancer. PMID- 2575487 TI - Criteria for aspiration cytology for the diagnosis of seminoma. AB - Fine-needle aspiration cytology was performed in two cases of intra-abdominal tumors, one from retroperitoneal lymph nodes and one from a cryptorchid testis. The cytological diagnosis was consistent with seminoma in both cases. Cytological features included uniform neoplastic malignant cells with round nuclei and nucleoli. The cytoplasm, easily observed on May-Grunwald-Giemsa-stained smears, contained large vacuoles or lacunes filled with glycogen. Alkaline phosphatase activity was strictly located to one cytoplasmic area of the cells. This cytological and cytoenzymatic pattern is different from that observed in other intra-abdominal tumors, including adenocarcinoma, large-cell lymphoma, and embryonal carcinoma. PMID- 2575486 TI - Human satellite III DNA: genomic location and sequence homogeneity of the TaqI deficient polymorphic sequences. AB - Human Satellite III DNA is a major tandem repeat in the human genome and presents a TaqI-specific hypervariable restriction fragment length polymorphism when a Satellite III related sequence (228S) is used as a probe. In situ examination shows this sequence to be near specific for the region 9qh on chromosome 9 when it is used at low probe concentrations. However the region 9qh does not appear to be the only or even the primary source of the TaqI-deficient polymorphic sequences (TDPS). Rather, such sequences appear to be mostly present in chromosomes 20, 21, and 22, and these represent the largest regions of homogeneous Satellite III in the genome; they are also resistant to digestion with a range of other restriction endonucleases. The TDPS do not arise from either of the two currently recognized Satellite III-enriched genomic regions, namely autosomal 'K-domains', which form part of 15p in chromosome 15 or the heterochromatin of chromosome Y. PMID- 2575488 TI - Differential regulation of oncogenic and cellular p185 by serine/threonine kinases. AB - 185c-neu is a member of a family of growth factor receptors with tyrosine kinase activity. A point mutation in the transmembrane region leads to activation of the enzymatic domain. We demonstrate that TPA (phorbol-12-myristate-13-acetate) stimulates the phosphorylation of p185c-neu on serine and threonine residues coincident with the inhibition of its intrinsic tyrosine kinase and the proliferation of cells that express it. The tyrosine kinase activity as well as the phosphorylation pattern of serine and threonine residues of oncogenic p185 (p185neu) and the growth of p185neu-expressing cells are not influenced by TPA. These observations indicate that the functional activity of p185c-neu can be regulated through protein kinase C (PKC) but the transmembrane point mutation present in p185neu renders it refractory to serine/threonine kinase regulation. PMID- 2575489 TI - A rapid procedure for cloning genes from lambda libraries by complementation of E. coli defective mutants: application to the fabE region of the E. coli chromosome. AB - I describe a general and rapid procedure allowing the isolation of specialized lambda transducing phages from a lambda library by lysogenic complementation of defective mutants of Escherichia coli. As an example, the cloning of the E. coli fabE gene and of two other adjacent genetic determinants is presented. Subcloning and determination of its nucleotide sequence reveals that fabE codes for the biotin carboxyl carrier protein (BCCP), one of the three subunits of acetyl coenzyme A carboxylase. PMID- 2575490 TI - Cloning of ovine insulin-like growth factor-I cDNAs: heterogeneity in the mRNA population. AB - We have isolated and characterized lamb liver cDNAs encoding ovine insulin-like growth factor-I (oIGF-I) precursor polypeptide to study IGF-I gene expression in ruminants. Four cDNA clones were sequenced revealing two different exon 1 sequences (designated 1A and 1B) and four different putative poly(A) adenylation sites. cDNAs containing exon 1A or exon 1B encode precursor polypeptides of 138 or 154 amino acids, respectively. A 130-amino-acid peptide is encoded by all cDNAs examined. These precursors include a hydrophobic leader peptide of varying lengths, the 70-amino-acid oIGF-I, and a 35-amino-acid carboxyl terminal extension peptide. The predicted amino acid sequence of the oIGF-I peptide differs from the human, bovine, and porcine IGF-Is at a single amino acid (at position 66, alanine is substituted for proline) and differs from rat and mouse IGF-Is at 4 and 5 positions, respectively. Both the amino- and carboxy-terminal extension peptides showed regions of extensive sequence homology. Ovine IGF-I amino-terminal peptides are 1 amino acid longer than other mammalian IGFs due to the presence of an extra amino acid (glutamine) present at the proposed boundary of exon 1 and exon 2. Northern blot analysis revealed multiple oIGF-I transcripts in a broad band at 800-1,100 nucleotides and other transcripts of higher molecular weight in liver. There was no detectable expression in either spleen or brain. PMID- 2575492 TI - Comparative pharmacokinetics of 3'-azido-3'-deoxythymidine (AZT) and 3'-azido 2',3'-dideoxyuridine (AZddU) in mice. AB - The pharmacokinetics of 3'-azido-3'-deoxythymidine (AZT) and 3'-azido-2',3' dideoxyuridine (AZddU, CS-87), active anti-HIV compounds, were characterized in uninfected mice. Sensitive and specific HPLC techniques were used to quantitate AZT and AZddU concentrations in serum and brain homogenates following iv doses of 50 mg/kg and 250 mg/kg. The pharmacokinetic parameters of t1/2, CIt, and Vss were similar for both compounds at each dose; however, CIt and Vss decreased at the higher dose, indicating a dose dependency. At the 50 mg/kg doses, the CIt of AZddU and AZT was 1.27 liters/hr/kg and 1.38 liters/hr/kg, respectively, which is analogous to the clearance value of AZT observed in humans. Brain/serum concentration ratios for AZddU tended to be greater than those obtained for AZT and were significantly different at the 50 mg/kg dose, being 0.234 +/- 0.282 for AZddU and 0.064 +/- 0.025 for AZT. PMID- 2575491 TI - Disposition and pharmacokinetics of naltrexone after intravenous and oral administration in rhesus monkeys. AB - The purposes of this investigation were to determine the disposition of naltrexone (NTX) in monkeys and assess the role of first-pass metabolism and enterohepatic cycling in the disposition process. Concentrations of naltrexone and three metabolites were determined in plasma and urine as a function of time after po and iv NTX administration in six monkeys. Urinary recovery of NTX and metabolites 0-48 hr after iv administration (10 mg/kg) totaled 52% of the dose. Recovery in feces was minimal. Total urinary excretion of NTX and metabolites after po administration was 89% of that after iv administration, suggestive of good absorption of NTX from solution. However, the area under the plasma level time curve for NTX after po administration was only 3.6% of that after iv administration, indicating a very high first-pass effect. The calculated extraction ratio was 0.96-0.99. Analysis of plasma level-time and urinary excretion rate-time data for NTX, conjugated NTX, beta-naltrexol, and conjugated beta-naltrexol after iv administration revealed that 1) the decline of plasma levels or urinary excretion rates with time for the conjugated metabolites was parallel to the decline for the apparent precursor; 2) the decline of plasma levels or urinary excretion rates for beta-naltrexol was slower than for naltrexone; and 3) there is evidence for a pronounced enterohepatic cycling of conjugated NTX and conjugated beta-naltrexol that influences the plasma level time profile of these conjugates and the unconjugated compounds as well. PMID- 2575493 TI - Pharmacokinetic analysis of cyclosporine in adjuvant arthritic rats. AB - Cyclosporine A (CsA) has been shown to be effective in patients with rheumatoid arthritis and to prevent the development and improve the symptoms of adjuvant induced arthritis in rats. Since abnormal drug disposition has been reported in inflammatory conditions, we have evaluated the pharmacokinetics of CsA in this animal model of arthritis. We found a statistically significant decrease in the rate of disappearance of blood concentrations of CsA following iv administration to arthritic rats. The plasma half-life of CsA increased with a corresponding decrease in total body clearance. The volume of distribution remained unchanged. This abnormality in CsA kinetics was not observed in these animals until 10 days after adjuvant injection. The administration of CsA (15 mg/kg ip) twice daily to arthritic rats for 8 days produced a 39.8% and 49.5% inhibition of swelling in the right and left hindpaw, respectively. There was also a 63.5% decrease in the arthrogram score. Trough levels of CsA in arthritic animals were initially higher than in controls during this treatment but returned to control values after 8 days of dosing, suggesting reversal of abnormal disposition with improvement of the disease. The addition of indomethacin to the dosing regimen resulted in a significant increase in trough levels of CsA, indicating a drug interaction between these two compounds. Possible mechanisms responsible for these observations with CsA are discussed. PMID- 2575494 TI - Enterohepatic circulation of T-2 toxin metabolites in the rat. AB - The enterohepatic circulation of T-2 toxin and its conjugated metabolites was examined in bile duct-cannulated male rats. Rats administered tritiated T-2 toxin intraduodenally (id) eliminated 44.65% and 57.25% of the administered dose in the bile within 4 and 8 hr post-dosing, respectively. TLC profiles of the T-2 metabolites were similar after intravascular and id administration. The major metabolites detected were 3'-OH-hydroxytryptamine-2 (HT-2), glucuronic acid conjugates, T-2 tetraol (TOL), 4-deacetylneosolaniol (4-DN), and HT-2. Tritium labeled glucuronides obtained from the bile of rats administered [3H]T-2 toxin intravascularly were extracted and purified using C-18 and silica column chromatography. Enzymatic hydrolysis followed by TLC and GC/MS indicated that the aglycone portion of the glucuronides were composed of 3'-OH HT-2, HT-2, 4-DN, and TOL. After id administration of the glucuronides the rats eliminated 6.01% (4 hr) and 11.86% (8 hr) of the dose in the bile. No free metabolites of T-2 toxin were detected in the bile of any animals administered the purified glucuronides. Oral treatment of the rats with the beta-glucuronidase inhibitor, saccharolactone, did not produce a significant decline in the amount of radioactivity recovered in the bile following administration of the tritium-labeled glucuronides. These studies substantiate the enterohepatic circulation of T-2 toxin metabolites. PMID- 2575495 TI - Metabolism of a nitrogen-containing steroid by rat hepatocytes and hepatic subcellular fractions. AB - Freshly isolated rat hepatocytes metabolized the nitrogen-containing steroid N,N diethyl-4-methyl-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta- carboxamide (I) to six products analyzed by reverse phase HPLC. The major metabolite, which could account for greater than 50% of the total I-related material, exhibited chromatographic, NMR, and mass spectral properties identical to those of the authentic 4-carbinolamide of I. Thus, the major biotransformation pathway in hepatocytes was hydroxylation of the N-methyl group of I to form a stable carbinolamide intermediate of N-demethylation. Desmethyl-I was observed as a minor metabolite. Another metabolite which accounted for approximately 10% of the total I-related material had chromatographic and spectral properties identical to those of the authentic monoethyl analog of I. The other three metabolites were formed in variable quantities and were unstable when isolated. Mass spectral data suggested that one metabolite was the carbinolamide intermediate of N deethylation. Treatment of rats with phenobarbital or dexamethasone increased the formation of the monoethyl metabolite of I in hepatocytes but had no effect upon the formation of the 4-carbinolamide metabolite. Rat hepatic microsomes catalyzed the NADPH-dependent metabolism of I to the same metabolites in the same relative amounts as observed with intact hepatocytes. Studies with alternative substrates and inhibitors demonstrated that microsomal cytochrome P-450 was responsible for the metabolism of I. Dog and human hepatic microsomes metabolized I to the same products as rat hepatic microsomes, but monoethyl I was the major metabolite. PMID- 2575496 TI - Metabolism, disposition, and mutagenicity of 2,6-diaminotoluene, a mutagenic noncarcinogen. AB - 2,6-Diaminotoluene (2,6-DAT) is a major industrial chemical; approximately 100 million pounds are used annually in the synthesis of 2,6-toluene diisocyanate. 2,6-DAT is mutagenic in Salmonella typhimurium TA98 requiring metabolic activation, but has been previously shown to be a noncarcinogen in male and female F344 rats and male and female 86C3F1 mice dosed orally in 2-year bioassays. 2,6-DAT was rapidly and extensively absorbed following oral administration, indicating that its lack of carcinogenicity is not due to poor absorption from the gastrointestinal tract. 2,6-DAT was also rapidly excreted, with 85% of 2,6-DAT-associated radioactivity being recovered in the urine within 24 hr. Resolution of the urine by reverse phase HPLC demonstrated the presence of four metabolites, but none of the parent 2,6-DAT. Therefore, the lack of carcinogenicity of 2,6-DAT is not due to lack of biotransformation in vivo. Following separation by HPLC, the metabolites were analyzed by electron impact and fast atom bombardment mass spectroscopy and by NMR spectroscopy. The metabolites were identified as a) 3-hydroxy-2,6-DAT, b) 4-hydroxy-2-acetylamino-6 aminotoluene, c) 2-acetylamino-6-aminotoluene, and d) 2,6-di(acetylamino) toluene. Metabolites b and d were found to be mutagenic in Salmonella typhimurium TA98 and then only in the presence of an activation system. Results of this study indicate that 2,6-DAT, which is a mutagen in in vitro tests, is also metabolized by the rat to compounds which are proximate mutagens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575497 TI - Biotransformation of etretinate and developmental toxicity of etretin and other aromatic retinoids in teratogenesis bioassays. AB - Developmental toxicity of the anti-psoriatic drug etretinate (Tegison) and some features of its metabolic conversion to etretin and isoetretin were investigated in in vivo and in vitro teratogenesis bioassays. We found that a single dose of etretinate administered orally to pregnant mice on day 11 of gestation was a potent teratogen (ED50 = 26 mg/kg). Etretin (acitretin, Neotigason), given as a single dose, was about 8-fold less active as a teratogen than etretinate. A ring substituted congener of etretinate, Ro 11-4768, was essentially inactive under similar conditions. Although the mechanisms which operate to make Ro 11-4768 inactive in teratogenesis are unknown and intriguing, it is suggested that the differences between etretinate and etretin may be dependent on individual pharmacokinetic characteristics. The in vitro chondrogenesis bioassay confirmed previous reports that the presence of an acidic endgroup was necessary for suppression of chondrogenesis, and that on that basis etretin was an active inhibitor of chondrogenesis, whereas etretinate was not. Introduction of esterase into the culture medium resulted in complete hydrolysis of etretinate and a quantitative conversion to acid congeners sufficient to account for an appropriate suppression in chondrogenesis. Although limb bud cells were virtually incapable of converting etretinate to etretin in the absence of exogenous esterase, they did influence the metabolism so that in the presence of esterase, isoetretin rather than etretin was the major endproduct of etretinate hydrolysis. Since etretinate therapy endangers the conceptus for a prolonged period of time even after cessation of therapy, further studies are necessary to determine the nature and the extent of hazard posed by the storage and/or metabolism of etretinate. PMID- 2575498 TI - Metabolism of the antianxiety drug buspirone in the rat. AB - The metabolism of an orally administered, 10-mg single dose of the antianxiety drug buspirone was studied in the rat. Samples of bile and urine were collected for 6 hr and were treated with beta-glucuronidase/arylsulfatase. The deconjugated metabolites were isolated and purified by HPLC. Structural analysis was carried out by combined gas chromatography/electron impact mass spectrometry as their trimethylsilyl derivatives and by 1H-NMR spectroscopy. Structures of the metabolites were further confirmed by co-elution on HPLC with authentic standards when possible. In addition to the already known metabolites 5-hydroxy-buspirone and 1-pyrimidinylpiperazine, seven major metabolites were unambiguously identified together with unchanged drug. Ten minor metabolites were partially characterized. Hydroxylation alpha to the glutaramidyl carbon at the 6'-position on the bicyclo ring system, hydroxylation on the pyrimidine aromatic ring, and N dealkylation of the butyl side chain were observed as major routes of metabolism. Minor routes of metabolism observed were: 3'-hydroxylation on the bicyclo ring system and formation of the methylated catechol derivatives. The identified metabolites accounted for greater than 90% of the total metabolites excreted in the rat bile and urine samples. PMID- 2575499 TI - Metabolism of the antianxiety drug buspirone in human subjects. AB - The metabolism of an oral dose (20 mg) of the antianxiety drug buspirone labeled with 14C/15N was studied in human subjects. 15N was incorporated in the molecule to facilitate structural characterization of the metabolites by mass spectrometry. Urine samples were collected at intervals up to 24 hr and analyzed for radioactivity. Cumulative urinary excretion accounted for 50% of the dose in 24 hr. The urine was hydrolyzed with beta-glucuronidase/arylsulfatase and the deconjugated metabolites were isolated and purified by HPLC. The purified metabolites were identified by GC/MS, 1H-NMR, and comparison with authentic standards when available. Seven metabolites of buspirone were identified unambiguously, together with unchanged drug. Hydroxylation alpha to the glutarimidyl carbonyl at the 6'-position on the spiro ring system, hydroxylation at the 5-position on the pyrimidine ring, and N-dealkylation of the butyl substituted side chain were major routes of metabolism. The identified metabolites accounted for 88% of the total radioactivity in the urine. A scheme for metabolism of buspirone in human subjects has been proposed. PMID- 2575500 TI - The pharmacokinetics of [3H]1-[1-(2-thienyl)cyclohexyl]piperidine (TCP) in Sprague-Dawley rats. AB - Using adult male Sprague-Dawley rats, we examined the blood protein binding and pharmacokinetics of the potent phencyclidine (PCP) receptor ligand 1-[1-(2 thienyl)cyclohexyl]piperidine (TCP). The average percentage of unbound [3H]TCP in rat serum was 42 +/- 6% and the [3H]TCP blood to plasma ratio was 0.98 +/- 0.03 (mean +/- SD, n = 5 in both studies). For the pharmacokinetic studies, [3H]TCP and 1 mg/kg unlabeled TCP were administered as an iv bolus dose. The average [3H]TCP elimination half-life was 2.1 hr. In contrast, total radioactivity in the plasma had a much longer half-life, suggesting much slower metabolite elimination. The average distribution volumes were 27 +/- 17, 15.6 +/- 6.2, and 5.6 +/- 3.0 liters/kg for V beta, Vss, and Vc, respectively. Total body and renal clearance values were 132 +/- 45 and 1.1 +/- 0.4 ml/min/kg, respectively. When TCP pharmacokinetic parameters were compared to PCP pharmacokinetic data in rats from a previous study, a strikingly similar pharmacokinetic profile was found. These data indicated that TCP and PCP are equivalent, from a pharmacokinetic point of view, and that the higher pharmacological potency of TCP over PCP is probably due to receptor-mediated differences. PMID- 2575501 TI - Influence of pregnancy on the pharmacokinetic disposition of two aromatic retinoids (etretinate and acitretin) in the rat. I. Intravenous studies. AB - The influence of pregnancy on the disposition of two related aromatic retinoids (etretinate and its metabolite, acitretin) was evaluated in a rodent model. The plasma concentrations of etretinate and acitretin were monitored by a specific HPLC method following iv bolus doses to 17-day pregnant and nonpregnant Sprague Dawley rats. The systemic clearance of etretinate was significantly lower in the pregnant rats compared to nonpregnant controls (129 vs. 185 ml/hr, respectively; p less than 0.05). This decrease was entirely due to a lower formation clearance of acitretin (acid) from etretinate (ester) in the pregnant animals (96 vs. 146 ml/hr; p less than 0.05). The in vitro plasma hydrolysis rate of etretinate was also lower in the pregnant animals. By contrast, the systemic clearance of acitretin was greater in the pregnant compared to the nonpregnant control animals (184 vs. 145 ml/hr, respectively; p less than 0.05). The apparent volumes of distribution for both retinoids were comparable in the pregnant and nonpregnant animals. Etretinate infusions in nonpregnant animals yielded systemic clearances (mean = 164 ml/hr) which were similar to those obtained for bolus dose experiments. Acitretin clearance increased (plasma levels decreased) following acitretin infusion to nonpregnant rats over the time course of the infusion. The results illustrate the marked effect of pregnancy on the disposition of these retinoids and suggest that acitretin may pose less of a teratogenic hazard than the parent compound etretinate. PMID- 2575502 TI - Influence of pregnancy on the pharmacokinetic disposition of two aromatic retinoids (etretinate and acitretin) in the rat. II. Single and multiple oral dosing studies. AB - During a multiple dose regimen of etretinate, steady state trough plasma concentrations of etretinate in nonpregnant female rats reached their peak levels (15 ng/ml) by day 10 and remained between 10 and 15 ng/ml through day 19. Steady state trough concentrations of acitretin in nonpregnant animals following etretinate multiple dosing reached their peak levels (53 ng/ml) at day 7 and declined to 16 ng/ml at day 19. A similar decline was observed following multiple oral dosing of acitretin itself, suggesting autoinduction of acitretin clearance. In single dose studies, the apparent oral bioavailability of etretinate was similar (4-5%) for both pregnant and nonpregnant rats (p greater than 0.05). The ratio of the AUC of acitretin to etretinate following etretinate administration was 10-fold greater than that reported for iv studies. Acitretin bioavailability was 10-fold greater than that for etretinate (57%); again, there was no difference between the pregnant and nonpregnant groups (p greater than 0.05). The apparent mean residence time and t1/2 of both etretinate and acitretin were similar for both groups (pregnant and nonpregnant). However, the time course of both etretinate and acitretin was greatly prolonged compared to iv studies. These studies suggest that the marked differences in the bioavailability (etretinate vs. acitretin) and in the time course of these retinoids (iv vs. oral) could have a substantial impact on their apparent toxicity. PMID- 2575503 TI - Metabolism, disposition, and pharmacokinetics of a potent anticonvulsant, 4-amino N-(2,6-dimethylphenyl)benzamide (LY201116), in rats. AB - The metabolism, disposition, and pharmacokinetics of 4-amino-N-(2,6 dimethylphenyl)benzamide (LY201116) have been studied in rats. 14C-LY201116 was well absorbed (approximately 94%) from the gastrointestinal tract following oral administration. Of the dose administered, 64.5% was excreted in the urine and 29% in the bile; with the majority being excreted during the first 24 hr. Peak plasma levels of LY201116 were observed at 0.75 hr, whereas peak plasma concentrations of radioactivity were seen at 2 hr after dosing. Maximum levels of radioactivity were observed at 2 hr in all of the tissues studied. The elimination of radioactivity from the tissues was monophasic with a mean half-life of 3.4 hr. Biotransformation of LY201116 in rats was investigated by quantitating and isolating metabolites from urine and plasma. The major route of metabolism was N acetylation to form 4-(acetylamino)-N-(2,6-dimethylphenyl)benzamide (ADMP), and subsequent hydroxylation to form 4-(acetylamino)-N-(2-hydroxymethyl-6 methylphenyl)benzamide (HADMP). Two hr after oral dosing with 14C-LY201116, ADMP and HADMP comprised 92% of the total radioactivity in the plasma. The major urinary metabolite, accounting for 63% of the radioactivity in the urine, was HADMP. The elimination of LY201116 from the systemic circulation following iv administration was monophasic, with a terminal t1/2 of 9.4 min. The volume of distribution was 911 ml/kg and the plasma clearance was 66.9 ml/min/kg. PMID- 2575504 TI - In vivo metabolism of isoxicam in rats, dogs, and monkeys. AB - Isoxicam is a long half-life nonsteroidal anti-inflammatory agent which undergoes extensive metabolism prior to elimination in animals and man. The major route of isoxicam transformation is hydroxylation of the methylisoxazole functionality to form hydroxymethylisoxicam, and cleavage of its benzothiazine moiety to give an oxoacetic acid metabolite. The metabolic pathway for scission of the benzothiazine moiety to the oxoacetic acid metabolite and to other potential metabolites is not known. To gain additional information on the metabolic fate of isoxicam, 14C-isoxicam labeled on the N-methyl group was administered to rats, dogs, and monkeys with urine and feces collected for metabolic profiling and identification. Identified as new metabolites of isoxicam were an open-ring sulfonamide, N-methylsaccharin, and saccharin. The formation of these metabolites suggests that isoxicam undergoes direct oxidative scission of its benzothiazine ring at carbon atom 3 to generate the observed open-ring sulfonamide, N methylsaccharin, and oxoacetic acid metabolites. PMID- 2575505 TI - Physiological disposition of CGS 16617 in rat, dog, and man. AB - The disposition and metabolism of CGS 16617 (3-[(5-amino-1-carboxy-1S pentyl)amino],2,3,4,5-tetrahydro-2-oxo-3S-1H-1 - benzazepine-1-acetic acid), and angiotensin l-converting enzyme inhibitor, were investigated in rats, dogs, and man. In rats, a single oral dose of 10 mg/kg 14C-CGS 16617 afforded peak plasma concentrations of drug between 0.5 and 6 hr of dosing. The AUC was on average 9.6% of that after iv administration of the same dose, indicating low oral absorption of the drug. The apparent volumes of distribution, V1 and Vdss, were 0.45 and 2.5 liters/kg, respectively. Disappearance of the drug from plasma after the iv dose was biphasic, with mean half-lives of 0.5 and 13 hr, respectively, for the lambda 1 and lambda 2 phases. After single iv doses (10 mg/kg) to dogs and rats, 14CGS 16617 was almost exclusively eliminated by the renal route, with urinary recoveries of greater than 90% of dose. The same dose administered orally gave urinary recoveries of less than 10% of the dose in rats and about 15% in the dog. The remainder of the dose was eliminated in the feces. Bile duct-cannulated rats excreted less than 3% of an oral 10 mg/kg dose in the bile, in 24 hr. In man (N = 4), a single oral dose of 100 mg 14C-CGS 16617 resulted in peak plasma concentrations of 0.02-0.07 microgram of drug eq/ml between 4 and 6 hr of dosing. The mean terminal half-life was estimated at 81 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575506 TI - Oral idazoxan bioavailability in rat. Relevance of intestinal and hepatic first pass effect. AB - The alpha 2-antagonist idazoxan (2-(2-(1,4-benzodioxanyl)-2-imidazoline) was administered iv, hepatoportally, and orally to Sprague-Dawley rats at 1, 3, and 10 mg/kg. Idazoxan plasma levels were determined by a HPLC method. A noncompartmental treatment of data was used to estimate the main pharmacokinetic parameters. After iv administration, idazoxan exhibited a linear kinetic profile. Half-life and mean residence time values ranged from 24.4 to 27.9 and from 34.2 to 40.5 min, respectively. Total plasma clearance values and volume of distribution at steady state values ranged from 0.057 to 0.078 (liters/kg)/min and 1.95 to 3.18 liters/kg, respectively. After the oral administration of idazoxan, time to peak values ranged from 5 to 10 min. When the oral 10 mg/kg dose was compared with both 1 and 3 mg/kg doses, significant statistical differences were observed in AUC levels and in dose-normalized peak concentration values (p less than 0.05, t test). Bioavailability values obtained after the oral administration of idazoxan ranged from 12.6 to 31.5%. The bioavailability range observed after the hepatoportal administration exceeded largely and significantly the range denoted after the oral route and displayed a saturable character already noted at the 3 mg/kg dose (p less than 0.01, t test). PMID- 2575508 TI - Biotransformation of 5-(2-chloroethyl)-2'-deoxyuridine in male NMRI mice. AB - When the selective anti-herpes agent [2-14C]-5-(2-chloroethyl)-2'-deoxyuridine [( 14C]CEDU) was administered as a single oral dose to mice, 87.9% of the radioactivity was excreted in the urine and 11.2% in the feces within 72 hr. Compounds accounting for 84% of the 14C radioactivity in the 0- to 24-hr urine were isolated by various chromatographic techniques and identified by MS, NMR, IR, and CD analysis. Approximately 25% of the radioactivity found in the urine was the parent compound (CEDU). According to the 14C-metabolites detected in the urine, one may infer that [14C]CEDU is metabolized, first, by cleavage of its N glycosidic bond, resulting in the formation of 5-(2-chloroethyl)uracil (38.7%) and, second, by stereoselective hydroxylation of the alpha carbon atom of the haloalkyl side chain of 5-(2-chloroethyl)uracil, resulting in the formation of 5 (1-hydroxy-2-chloroethyl)uracil (29.6%). CEDU was absorbed rapidly from the gastrointestinal tract and the bloodstream, and did not show any particular accumulation in mouse tissues, as revealed by whole body autoradiography. PMID- 2575507 TI - Dose-related effects of phenobarbital on hepatic glutathione-S-transferase activity and ligandin levels in the rat. AB - To determine which individual parameters contribute to the increased bilirubin clearance which follows phenobarbital administration in the rat, dose response studies are being conducted relating changes in various aspects of bilirubin transport to the dose of phenobarbital administered. The relationships between phenobarbital dose, immunoreactive ligandin concentrations, and cytosolic glutathione-S-transferase (GSHT) enzymatic activities were determined in the 100,000g liver cytosol obtained from non-fasted male Sprague-Dawley rats, treated for 6 days (ip) with either phenobarbital at various doses ranging from 1 to 125 mg/kg/day or distilled water. Ligandin levels were measured by radioimmunoassay employing an antiserum which reacts with both GSHT-1 (Ya) and -2 (Yc) subunits. Ligandin concentration increased in a dose-dependent fashion, achieving a maximal observed value of 278% of control at the highest administered phenobarbital dose. Values were significantly elevated compared to controls at doses as low as 3 mg/kg/day. GSH-dependent delta 5-3-ketosteroid isomerase (KSI) activity, which reflects predominantly GSH transferase subunit 1, and GSHT activity against 1 chloro-2,4-dinitrobenzene (CDNB) also increased over the entire range of phenobarbital doses administered. Both of these enzymatic activities were highly correlated with immunoreactive ligandin levels (KSI: r = 0.89, p less than 0.005; GSHT (CDNB): r = 0.92, p less than 0.001). By contrast, GSHT activity against 1,2 dichloro-4-nitrobenzene (DCNB), which resides principally on GSHT subunits not present in ligandin, did not correlate significantly with measured ligandin concentrations. These studies indicate that phenobarbital is capable of inducing immunoreactive ligandin concentrations and related enzymatic activities at doses as small as 5% of those commonly employed to demonstrate this effect. PMID- 2575509 TI - The uptake of clodronate (dichloromethylene bisphosphonate) by macrophages in vivo and in vitro. AB - Clodronate (dichloromethylene bisphosphonate) accumualtes extensively in the bone by binding to apatite crystals. We found recently that the drug also accumulates in the spleen and, to a lesser extent, in the liver of mice and rats. In the present study, the role of macrophages in soft tissue accumulation was studied in mice by autoradiography and macrophage-depleting techniques, and also by isolated rat peritoneal macrophages. The localization of [14C]clodronate in mouse spleen showed that the drug concentrates in the marginal zone between the white and red pulp, which is known to be rich in macrophages. Pretreatment of mice with pure clodronate did not change the accumulation of [14C]clodronate in the spleen. However, when splenic and hepatic macrophages were eliminated by the liposome encapsulated clodronate, only a weak [14C]clodronate accumulation occurred in these organs. Isolated macrophages did not take up free [14C]clodronate, but the addition of ferrous iron to the incubate resulted in the uptake of 14C activity by macrophages. They were probably stimulated by the insoluble clodronate-iron complex. The results suggest that 1) macrophages are involved in the accumulation of clodronate in the spleen and liver, and 2) combination of clodronate with extracellular iron is a prerequisite for the activation of macrophages to take up the drug complex. Since the spleen and, to a lesser extent, the liver are rich in iron released from destroyed red cells, accumulation of clodronate takes place in these organs. PMID- 2575510 TI - Sensitivity of the rat liver microsomal oxidation of pyrazole to antibody raised against the ethanol-inducible rabbit liver cytochrome P-450 isozyme. AB - Pyrazole is oxidized to 4-hydroxypyrazole by rat liver microsomes in a cytochrome P-450-dependent reaction and this oxidation can be increased by prior treatment of rats with pyrazole, 4-methylpyrazole, or chronic ethanol feeding. The induction pattern suggests that pyrazole may be an effective substrate for oxidation by P-450 IIE.1. This P-450 isozyme is recognized by antibody (anti-3a IgG) raised against the ethanol-inducible P-450 in rabbits. Experiments were carried out to evaluate the ability of anti-3a IgG to inhibit pyrazole oxidation by microsomes from controls and from rats treated with inducers of P-450 IIE.1. Immunoblots with anti-3a IgG or with the anti-pyrazole P-450 IgG were identical and indicated increased staining of the pyrazole P-450 with microsomes from rats treated with pyrazole, 4-methylpyrazole, or ethanol, relative to saline controls; very little staining occurred with microsomes from pair-fed controls or phenobarbital-treated rats. Rates of pyrazole oxidation were highest with microsomes from rats treated with the inducers of P-450 IIE.1 and lowest with pair-fed controls or rats treated with phenobarbital. Anti-3a IgG produced about a 60% decrease of pyrazole oxidation in microsomes from rats treated with inducers of P-450 IIE.1 and about a 25% decrease with the saline controls; no inhibition was found with microsomes from the phenobarbital-treated rats. The anti-3a IgG-resistant rate of pyrazole oxidation was similar with all the microsomal preparations, and was not due to interaction of pyrazole with hydroxyl radicals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575511 TI - Disposition of sandostatin, a new synthetic somatostatin analogue, in rats. AB - The distribution, excretion, and metabolism of Sandostatin, a long-acting octapeptide analogue of somatostatin, have been studied in the rat after iv administration. Similar plasma levels and excretion values were observed by using radioimmunoassay and HPLC-liquid scintillation techniques. For the latter technique Sandostatin was radiolabeled with either 14C or 3H. The plasma pharmacokinetics of Sandostatin were as follows: Vdss = 0.4 liter/kg, C/t = 4.2 ml/min, and t1/2 2.0 hr; this half-life was by far longer than that of somatostatin. The in vitro protein binding amounted to 59% in rat plasma; no Sandostatin was taken up by blood cells. The tissue concentrations of Sandostatin were similar when determined either by radioimmunoassay or by quantitative whole body autoradiography; this suggests that the distribution of 3H or 14C radioactivity observed 0.5 hr after iv administration mostly represented unchanged Sandostatin. Kidney and liver were the only tissues in which Sandostatin levels were higher than in blood; high radioactivity levels were observed in the blood vessel walls, whereas levels in brain were insignificant. Unchanged drug accounted for most of the radioactivity found in plasma, urine, and bile, whereas only traces of unchanged drug were detected in feces. These results demonstrated the metabolic stability of Sandostatin in the tissues, primarily in the liver, and suggested an extensive degradation in the intestinal tract. The degradation products consisted of smaller peptides and free amino acids. About 50% and 20% of the applied dose were excreted as unchanged Sandostatin in bile and urine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575512 TI - Amiodarone-digoxin interaction in rats. A reduction in hepatic uptake. AB - The interaction amiodarone-digoxin results in a marked increase in the digoxin serum concentrations. The mechanism of this interaction is still unexplained. The influence of amiodarone on digoxin hepatic extraction in rats was investigated. The digoxin hepatic extraction coefficients were determined using the isolated perfused livers of control and amiodarone-treated (25, 50, and 100 mg/kg/day for 5 days) rats. When plotted as a function of time, an inverse relationship between the extraction coefficients and the dose of amiodarone was evident. Significant dose-related reductions were observed in hepatic clearances calculated after 16 and 20 min of digoxin infusion when steady state was achieved. Analysis of the hepatic effluent by HPLC revealed only digoxin in the effluent of both control and amiodarone-treated rats; no metabolites were detected. Using liver homogenates, no differences were found in the ability of control or amiodarone treated (50 mg/kg/day for 5 days) rats to metabolize digoxin. These changes occur without significant lesion of the hepatocytes, inasmuch as the serum concentrations of glutamic-pyruvic and glutamic-oxaloacetic transaminases were not affected by the administration of amiodarone (50 or 100 mg/kg/day for 5 days). Furthermore, a microscopic study of the hepatocytes revealed light cytoplasmic vacuolization, normal Kupffer cells, and no evidence of macrophage proliferation. It was concluded that amiodarone increases digoxin serum concentrations by inhibiting its uptake into the hepatocytes. PMID- 2575513 TI - Regional differences in adrenal activation of spironolactone: relationship to steroid 17 alpha-hydroxylase activity. PMID- 2575515 TI - Expression pattern of homeobox-containing genes during chick embryogenesis. AB - We have isolated, sequenced and examined the expression pattern of two tandemly arranged homeobox-containing genes from the chicken. The predicted amino acid sequences of the homeodomain and the adjacent carboxyterminal portion of the protein of the first gene is virtually identical (99%) to that of murine homeobox 2.1 and hence we refer to it as Ghox 2.1 (Gallus homeobox). The closest mouse homologue of the second homeodomain is Hox 2.2 (95% identical within the homeobox), and hence referred to as Ghox 2.2. Northern analysis of embryonic RNA reveals major transcripts of 2 kb for Ghox 2.1 and 1.7 kb for Ghox 2.2. To investigate the transcript pattern, embryos of various stages were dissected into heads, trunks and limb buds and the RNA was analysed by Northern blotting and RNase protection assays. Ghox 2.1 transcripts are present in all three regions. Ghox 2.2 RNA is found in trunks and limb buds, but it is strikingly absent from the developing head. In situ hybridization with 35S-labelled antisense riboprobes derived from Ghox 2.1 demonstrates that this gene is expressed at high levels in spinal chord, myelencephalon and mesonephros. Dorsal root ganglia and the lung rudiment also contain Ghox 2.1 message, but in somewhat lower amounts. Mid- and forebrain, the heart, presomitic mesenchyme and notochord do not contain detectable levels of Ghox 2.1 mRNA. Of particular interest is the expression of Ghox 2.1 in a well-defined patch of mesenchymal tissue situated in an anterioproximal region of the limb bud. PMID- 2575514 TI - Octopod, a homeotic mutation of the moth Manduca sexta, influences the fate of identifiable pattern elements within the CNS. AB - Octopod (Octo) is a mutation of the moth Manduca sexta, which results in the homeotic transformation of the ventral surface of the first (A1) and less often the second (A2) abdominal segments in the anterior direction. The extent of the transformation ranges from a slight deformation of the ventral cuticle, up to the formation of miniature thoracic legs on A1. The extent of the transformation is always less within A2 as compared to A1. A genetic analysis revealed that Octo is an autosomal mutation which shows incomplete dominance. The effect of this mutation on the central nervous system (CNS) was assessed by examining the distribution and fate of the postembryonic neuroblasts in the segmental ganglia of Octo larvae. In each of the thoracic ganglia of wild-type larvae, there is a set of 45-47 neuroblasts; a reduced but homologous array of 24 and 10 neuroblasts are found in A1 and A2, respectively. Ganglion A1 of Octo larvae had 1 to 6 supernumerary neuroblasts, and 20% of the A2 ganglia showed a single ectopic neuroblast. The supernumerary neuroblasts corresponded to identifiable neuroblasts normally found in more anterior ganglia. The Octo mutation also influenced the mitotic activity of stem cells normally present in A1. In this case, the neuroblasts generated a lineage of cells that were typical of a thoracic location rather than A1. These data demonstrate that homeotic mutations can influence the fate of identifiable pattern elements within the CNS of an insect. PMID- 2575516 TI - Genetic structure of the abd-A gene of Drosophila. AB - We report the embryonic and adult phenotypes of a number of mutations of the abd A gene of the bithorax complex. Some of them result in loss of abd-A function in the whole abd-A domain and are usually lethal. These probably eliminate or inactivate abd-A protein products. Other mutations affect only part of the abd-A domain. These are viable, appear to map outside the abd-A transcription unit, and presumably alter the normal spatial regulation of abd-A products. We propose a model of abd-A structure based on a protein-coding region and two cis-regulatory regions. Regulatory region 1, 3' to the transcription unit, contains positive and negative regulatory elements. Regulatory region 2, 5' to the transcription unit, establishes the correct level of abd-A activity in the abdominal metameres. PMID- 2575518 TI - A theoretical study of glucosamine synthase. Part I. Molecular mechanics calculations on substrate binding. AB - Glucosamine synthase transfers the gamma-amino group of glutamine to fructose, producing 1-glucosamine which is the key constituent of bacterial and fungal cell walls. In this study, model calculations were performed on substrate binding to the enzyme active site. Two models of the active site of glucosamine synthase were proposed, which assume two different sequences of aminoacids, Cys-Gly-Ile and Cys-Ala-Cys, the first one being the N-terminal sequence of the Escherichia coli enzyme. Several initial geometries were assumed for these tripeptides, the energy was then optimized by means of molecular mechanics. It has been found that the structure which is both energy optimal and satisfies the assumed cysteine sulphur arrangement consists of combinations of C7eq and C7ax conformations of single residues. Molecular mechanics calculations were then performed on glutamine and D-fructose-6-phosphate, which are the substrates of the enzymatic catalysis, and on their complex with the enzyme glutamine-binding site. The spatial configuration of the compounds under study, which is optimal as far as the reaction path is concerned, also turned out to be an energy minimum. PMID- 2575517 TI - [Melatonin and schizophrenia]. AB - Many research studies have been conducted with melatonin, a pineal hormone, in psychiatry. Studies with melatonin in schizophrenic patients are rare. Blood plasma samples were drawn at 24 hours and 12 hours in 23 schizophrenic subjects and 26 controls, during the same season. Plasma melatonin levels were obtained using a specific radioimmunoassay technique. The 24 hours levels significant decreased in schizophrenic patients compared with controls (p less than 0.01). Methodology, specificity of results and concomitant study of cortisol levels are discussed. PMID- 2575519 TI - Effects of NMDA antagonists on picrotoxin-, low Mg2+- and low Ca2+-induced epileptogenesis and on evoked changes in extracellular Na+ and Ca2+ concentrations in rat hippocampal slices. AB - The anticonvulsant properties of ketamine and 2-APV were compared on 3 types of convulsant activity in hippocampal area CA1: the 'picrotoxin-epilepsy,' the 'low magnesium epilepsy' and the 'low calcium epilepsy.' In particular the spontaneous activity, the synaptically evoked responses and the changes in [Ca2+]0 were examined, since in many cases of epilepsy, Ca2+ uptake into cells is enhanced. In normal medium, ketamine and 2-APV have nearly no effect on stimulus evoked decreases in [Ca2+]0, although they clearly depress NMDA-induced ionic changes. However, ketamine and 2-APV prevent to some extent the augmentation of stimulus induced changes in [Ca2+]0, observed after treating slices with picrotoxin or Mg2+-free medium. This extra Ca2+ uptake is probably mediated by NMDA operated channels. Our findings also show that ketamine, like 2-APV, has a stronger anticonvulsant effect on the low Mg-than on the picrotoxin-induced epileptiform activity. Responses to iontophoretically applied NMDA are facilitated in the 'low calcium epilepsy' and can be selectively blocked by ketamine. Spontaneous epileptiform activity occurring in low calcium can be blocked by ketamine only when some synaptic transmission is still present. PMID- 2575520 TI - Pharmacological approaches in the treatment of senile dementia. AB - The pathogenesis of primary degenerative dementia is still unknown and current therapeutic approaches can aim only at ameliorating some of the symptoms associated with this brain disease. At present, most approaches, attempt to correct a cholinergic deficit. Although the therapeutic benefits obtained so far with currently available cholinergic drugs are generally modest, it appears that there exists a subgroup of responders. This offers some hope that more potent and more selective cholinergic drugs might be more effective. Recent findings suggest that the neurochemical pathology in degenerative dementia is not restricted to the cholinergic system but also includes pathways using monoamines as transmitters. Alternative strategies should therefore include drugs able to correct disturbances in monoaminergic systems. Hydergine and the novel drug CBM 36-733 are suitable candidates. Hydergine is approved by the FDA as being effective for the treatment of selected symptoms of cognitive decline in the elderly. Preliminary results of a 2-month study indicate that CBM 36-733 has beneficial effects in patients with mild to moderate degrees of degenerative dementia. Interestingly, CBM 36-733 also counteracts age-related decreases in choline acetyltransferase, a marker for cholinergic nerve terminals in experimental animals. It will therefore be of interest to clinically evaluate in long-term studies the potential of this drug to slow down the progression of neurodegenerative processes. PMID- 2575522 TI - The pharmacokinetics of clotiazepam after oral and sublingual administration to volunteers. AB - We have studied the single dose pharmacokinetics of 5 mg clotiazepam drops, oral tablets, and sublingual tablets in a cross-over study in 6 healthy volunteers (median age 28 years). The formulations had similar systemic availability. Compared with oral tablets the sublingual route gave a lower peak concentration and a delayed peak time, while drops gave a greater maximum concentration with a similar peak time. The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially in the elderly. PMID- 2575523 TI - The alpha 2-adrenoceptor antagonists idazoxan and yohimbine can unmask the postsynaptic dopamine agonist effects of B-HT 920. AB - Administration of B-HT 920 alone produced weak stereotypy in a small percentage (4-8%) of rats. In contrast, after combined administration of idazoxane and B-HT 920, stereotyped behaviors (sniffing and licking) were consistently produced in all rats. The appearance of stereotypy after combined treatment with yohimbine and B-HT 920 was inversely related to the dose of yohimbine. These data suggest that the alpha 2-adrenoceptor agonist effects of B-HT 920 can mask it's postsynaptic dopamine agonist effects. PMID- 2575521 TI - Evaluation of the metabolic responses to inhaled salbutamol in the measurement of beta 2-adrenoceptor blockade. AB - The aim of the present study was to evaluate whether metabolic responses to inhaled salbutamol may be used to measure the cardioselectivity of beta adrenoceptor antagonists. We therefore studied the effects of oral doses of atenolol 50 mg, 100 mg, 200 mg (A50, A100, A200), propranolol 40 mg (P40), and placebo (Pl) on the hypokalaemic (K) and hyperglycaemic (Glu) responses to inhaled salbutamol in five healthy subjects. Increasing doses of atenolol were associated with a progressive attenuation of delta K compared with placebo: -0.72 mmol.l-1 (Pl) vs -0.20 mmol.l-1 (A200). However, delta K with A200 was significantly different from the response with P40: +0.12 mmol.l-1. There were partial reductions in the hyperglycaemic response with the beta-adrenoceptor antagonists, although this was only significant (compared with Pl) for P40: delta Glu 1.92 mmol.l-1 (Pl) vs 0.76 mmol.l-1 (P40). These results show that beta 2 adrenoceptor blockade by atenolol is a dose-dependent phenomenon, which may be measured by the attenuation of salbutamol-induced hypokalaemia. However, beta 2 adrenoceptor blockade by atenolol 200 mg was less than that by propranolol 40 mg. The glucose response to salbutamol was only partially blocked by propranolol and may therefore not be suitable to assess beta 2-adrenoceptor antagonism. PMID- 2575524 TI - Clonidine produces mydriasis in conscious mice by activating central alpha 2 adrenoceptors. AB - Intraperitoneal (i.p.) injection of the alpha 2-adrenoceptor agonist clonidine (1 3000 micrograms/kg) produced dose-dependent pupil dilatation in conscious C57/Bl/6 mice with an ED50 of 54 micrograms/kg (95% confidence limits 40-74 micrograms/kg). This response was rapid in onset and of approximately 30 min duration. The alpha 2-adrenoceptor antagonists idazoxan (1 or 3 mg/kg i.p.) and yohimbine (1 or 3 mg/kg i.p.) both produced dose-related miosis, but the alpha 1- and beta-adrenoceptor antagonists prazosin (1 or 3 mg/kg i.p.) and pindolol (1 or 3 mg/kg i.p.) were without effect. These doses of idazoxan and yohimbine potently reversed the mydriasis induced by clonidine (100 micrograms/kg i.p.), while prazosin and pindolol were again ineffective. Clonidine-induced mydriasis was also unaltered by the 5-HT antagonists, methysergide (2.5 mg/kg i.p.) and ketanserin (0.1 mg/kg i.p.) or 0.1 mg/kg i.p. of the dopamine antagonists, haloperidol, SCH 23390 and BRL 34778. A dose of 0.25 microgram clonidine, which was ineffective when administered i.p., produced marked mydriasis after intracerebroventricular (i.c.v.) injection. In addition, the mydriasis produced by i.p. injection of clonidine (100 micrograms/kg) was abolished by i.c.v. dosing of 2.5 micrograms idazoxan or yohimbine, but again not by prazosin or pindolol. Together, these data provide strong evidence to indicate that clonidine-induced mydriasis is exclusively mediated via central alpha 2-adrenoceptors and that this response provides a useful model for studying the function of these receptors. PMID- 2575525 TI - A direct non-opiate interaction of dynorphin-(1-13) with the N-methyl-D-aspartate (NMDA) receptor. PMID- 2575526 TI - Identification of 5-HT1A recognition sites in human ganglioneuroblastoma. PMID- 2575527 TI - Effects of a peripherally acting alpha 2-adrenoceptor antagonist (L-659,066) on hemodynamics and plasma levels of catechols in conscious rats. AB - L-659,066 is a new alpha 2-adrenoceptor antagonist which does not enter the central nervous system after systemic administration and therefore can be used to examine effects of blockade of peripheral alpha 2-receptors on hemodynamics and plasma levels of catechols. After i.v. administration to conscious rats, L 659,066 produced dose-related, small decreases in mean arterial pressure (MAP) and large increases in heart rate (HR), arterial plasma levels of norepinephrine (NE), and levels of the intraneuronal NE metabolite, dihydroxyphenylglycol (DHPG). After administration of L-659,066, HR, but not MAP, was strongly correlated with NE levels (r = 0.93, P less than 0.001). Levels of DHPG and dihydroxyphenylalanine (DOPA) also were strongly correlated with NE levels (r = 098 and r = 0.71). After comparison with responses during hypotension induced by the vasodilator, nitroprusside, the results indicated that L-659,066 increases sympathetically mediated NE release and catecholamine turnover due to inhibition of presynaptic alpha 2-receptors as well as due to reflexive sympathetic activation related to blockade of alpha 2-receptors on arterial smooth muscle cells. PMID- 2575528 TI - Activation of alpha 2-adrenoceptors attenuates the inotropic effect of field stimulation in atria. AB - Guinea-pig left atria were driven to contract at a rate of 0.5 Hz by stimulation with punctate electrodes. For additional field stimulation, a train of one to eight field pulses (30 V; 0.05-0.4 ms duration) was applied during each refractory period. Cholinergic effects were blocked by atropine and thus the resulting increase of the contractile force was caused by noradrenaline released from sympathetic nerve endings. Trains of several short field pulses delivered in the refractory period after each contraction produced a significantly greater inotropic effect than one single pulse of the same total duration delivered in each refractory period. Phentolamine, rauwolscine and idazoxan, by blocking prejunctional alpha 2-adrenoceptors selectively increased the inotropic effect of single field pulses. Selective blockers of alpha 1-adrenoceptors (prazosin, corynanthine) were ineffective in this respect. The effect of alpha 2 adrenoceptor blockers persisted in the presence of noradrenaline uptake blockers (cocaine or desipramine plus corticosterone) or phenylephrine, but was overcome by the alpha 2-adrenoceptor agonists, clonidine and guanabenz. It is concluded that activation of presynaptic alpha 2-adrenoceptors limits the release of noradrenaline by long-lasting single field pulses. Autoinhibition of transmitter release was not seen with trains of short field pulses. PMID- 2575530 TI - The neuropeptide, Org 5878 (desenkephalin-gamma-endorphin, DE gamma E), affects local cerebral glucose utilization in freely moving rats. AB - The effect of the antipsychotic peptide, Org 5878 (desenkephalin-gamma-endorphin, beta-endorphin-(6-17), on local cerebral glucose utilization was studied in freely moving male Wistar rats. Org 5878 (20 micrograms/kg, i.v.) or saline were given acutely and local cerebral glucose utilization was measured in 116 brain structures. Glucose uptake was not altered by Org 5878 in most brain areas, including areas of the nigrostriatal system, the cortex and the thalamus. However, significant reductions in glucose uptake were observed in the ventral tegmental area, the diagonal band complex, the hippocampus, the amygdala, the interpeduncular nucleus, the reticular nucleus of the thalamus and the cerebellum. These results indicate that the nigrostriatal and cortico-thalamic systems remain unaffected but the activity of the mesolimbic ventral tegmental area and of major target areas of cholinergic basal forebrain structures is selectively reduced following Org 5878 administration. It is concluded that the effect of Org 5878 on local cerebral glucose utilization is distinct from and more selective than that of antipsychotics currently used in the clinic. PMID- 2575529 TI - Pulse duration and alpha 2-adrenoceptors modify noradrenaline release from field stimulated atria. AB - In guinea-pig atria preloaded with 10 muCi [3H]noradrenaline, field stimulation during the refractory period increased the release of radioactivity and the force of contraction. Both effects were dependent on the extracellular Ca2+ concentration and were abolished by 3 x 10(-8) mol/l tetrodotoxin. When applied during each refractory period, two short (0.05 ms) pulses released significantly more radioactivity than one pulse of 0.1 ms duration applied during each refractory period. Similarly, a train of four pulses (0.05 ms each) was more effective than one pulse lasting 0.2 ms. The radioactivity released by single, long-lasting pulses in each refractory period was increased by phentolamine, idazoxan and N-ethylmaleimide. A small increase was also obtained with prazosin. The effect of phentolamine was antagonized by clonidine but not by phenylephrine. Clonidine did not prevent the effect of N-ethylmaleimide (all drugs 3 x 10(-5) mol/l; atropine 10(-7) mol/l and cocaine 3 x 10(-6) mol/l present in all experiments). It is concluded that activation of prejunctional alpha 2 adrenoceptors reduces the amount of noradrenaline release by one long field pulse in each refractory period. In most experiments, the inotropic effect of the two stimulation protocols was not significantly different. However, when atria were stimulated with four pulses immediately before stimulation with one pulse, the autoinhibition thus caused was strong enough to also reduce the inotropic effect of this stimulation protocol. PMID- 2575531 TI - Beta-adrenoceptor-mediated cAMP accumulation in cardiac cells: effects of nebivolol. AB - The effects of nebivolol, the racemic mixture of the SRRR and RSSS enantiomers, on beta-adrenoceptor-mediated cAMP accumulation in living cardiac cells were compared to those of beta-adrenoceptor antagonists. Serum-free cultivation of cardiac cells from ventricles of 2 to 3-day-old Wistar rats resulted in a population of contractile cardiac cells almost free of mesenchymal non-myocardial cells. Isoproterenol stimulated beta 1- as well as beta 2-adrenoceptor sites. Selective beta 1- and beta 2-receptor site occlusion, in the presence of an appropriate concentration of the selective beta 2-adrenoceptor antagonist, ICI 118-551, or the selective beta 1-adrenoceptor antagonist, CGP 20712-A, showed that the receptor population consisted of mostly the beta 1-adrenergic subtype. The latter could be specifically stimulated by noradrenaline. Nebivolol and d nebivolol (SRRR) inhibited noradrenaline-induced cAMP accumulation with IC50 values of 22 and 15 nM, respectively. CGP 20712-A was 10 times more active and atenolol was 7 times less active than nebivolol. Both assays, beta-adrenoceptor binding and cAMP accumulation, evidenced beta-adrenoceptor antagonistic properties only for the d-enantiomer of nebivolol (SRRR). 1-Nebivolol (RSSS) showed no beta-adrenergic activity. PMID- 2575532 TI - The effects of the enantiomers of the dopamine agonist N-0437 on food consumption and yawning behaviour in rats. AB - The enantiomers of the potent and selective dopamine (DA) D-2 receptor agonist 2 (N-propyl-N-thienylethyl-amino)-5-hydroxytetralin, N-0437, were tested for their effects on palatable food consumption and yawning behaviour in rats. (-)-N-0437 (1.0 and 5.0 mumols/kg). This confirms the agonistic action of (-)-N-0437 on postsynaptic receptors as food consumption is considered to be related to stimulation of postsynaptic DA receptors. Yawning behaviour was stimulated by (-) N-0437 (0.5 mumol/kg) and could be antagonized by the autoreceptor-selective antagonist (+)-UH 232 (25 mumols/kg), which suggests an agonistic action on DA autorecptors. (+)-N-0437 (5.0 and 10.0 mumols/kg) also reduced food consumption and the effect could be antagonized by YM 09151-2 (0.03 mumol/kg). The weaker effect of (+)-N-0437 on food intake in comparison to that induced by (-)-N-0437 can be explained if it assumed that (+)-N-0437 is a partial agonist. (+)-N-0437 did not induce yawning behaviour in rats, suggesting that autoreceptors mediating the release of DA may be involved in stimulating yawning by DA agonists. PMID- 2575533 TI - Antigen challenge modifies the cyclic AMP response of inflammatory mediators and beta-adrenergic drugs in alveolar macrophages. AB - Adenylate cyclase activity was determined in alveolar macrophages (AMs) obtained from bronchoalveolar lavage (BAL) fluids of naive and antigen-challenged guinea pigs. After the anaphylactic reaction in ovalbumin-sensitized guinea pigs, the basal levels of cyclic AMP in AMs were significantly increased compared to the levels in naive AMS (1.87 +/- 0.22 versus 5.26 +/- 0.45 pmol cyclic AMP/5.10(6) cells). Prostaglandin E2 (PGE2), prostacyclin (DC-PGI2), histamine, isoprenaline and salbutamol stimulated adenylate cyclase activity more effectively in AMs obtained from sensitized guinea pigs after the booster injection compared to AMs obtained from non-treated animals. Moreover, DC-PGI2 and histamine, which were hardly able to induce a rise in cyclic AMP levels in naive AMs, become effective activators in AMs obtained after antigen challenge (100 and 60% increase in the response, respectively). Using selective receptor ligands, we have shown that beta 2-adrenoceptors and H2-subtype histamine receptors are functionally coupled to macrophage adenylate cyclase activity. The present data indicate that sensitization does not affect the configuration of the receptor on the outer membrane (no change in affinity constants), but affects other parts of the transmembrane signal system leading to the intracellular production of cyclic AMP (e.g. regulatory binding proteins or increases in the number of receptors). PMID- 2575534 TI - Stimulation of alpha 1-adrenoceptors increases electrically evoked [3H]acetylcholine release from the rat phrenic nerve. AB - The modulation by sympathomimetic amines of the electrically evoked [3H]acetylcholine release from the motor nerve was investigated. Phenylephrine (10 mumol/l), alpha-methylnoradrenaline (10 mumol/l) and adrenaline (1 mumol/l) enhanced the electrically evoked [3H]acetylcholine release from the rat phrenic nerve. The enhancing effect of phenylephrine was completely prevented by low concentrations of prazosin (0.1 or 0.01 mumol/l) whereas a high concentration of yohimbine (1 mumol/l) was necessary to abolish the effect of phenylephrine. The simultaneous blockade of alpha- and beta-adrenoceptors, i.e. propranolol (0.1 mumol/l) together with prazosin (0.01 mumol/l) or yohimbine (1 mumol/l), was required to abolish the enhancing effect of alpha-methylnoradrenaline. Likewise, the enhancing effect of adrenaline could be abolished only by a combination of two antagonists (propranolol together with yohimbine or prazosin). Neither clonidine nor oxymetazoline (1 or 10 mumol/l) modulated the evoked [3H]acetylcholine release. The experiments showed the existence of alpha adrenoceptors which are present on the motor nerve and whose stimulation mediates an increase in evoked transmitter release. The different potencies found for prazosin and yohimbine indicate that an alpha 1-subtype of the receptors was involved. Increased sympathetic activity may facilitate neuromuscular transmission by stimulation of presynaptic alpha- and beta-adrenoceptors. PMID- 2575535 TI - Two pharmacological classes of quisqualate-induced electrical responses in rat retinal ganglion cells in vitro. AB - The pharmacological properties of steady state responses elicited by the excitatory amino acid agonists quisqualate and alpha-amino-3-hydroxy-5 methylisoxazole-4-propionate (AMPA) have been examined in isolated rat retinal ganglion cells with patch electrodes. Based upon testing retinal ganglion cells with both agonists at saturating concentrations (30 microM for quisqualate and 60 microM for AMPA), these neurons can be grouped into three different categories: (a) type I cells, in which AMPA steady state responses were larger than those induced by quisqualate; (b) type II cells, in which quisqualate steady state responses were larger than or equal to those produced by AMPA; and (c) type III cells, in which neither AMPA nor quisqualate elicited responses. Regardless of cell type (I or II), AMPA responses were substantially inhibited by the antagonists kynurenate (750 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM). In contrast, the effects of these antagonists on quisqualate responses varied depending on the cell type, with both kynurenate and CNQX being more effective in type II than in type I cells. Based upon further pharmacological manipulations, it is proposed that quisqualate-induced steady state responses in retinal ganglion cells are divisible into two pharmacological classes that exist in varying proportions in these cells in vitro. PMID- 2575537 TI - Cholinergic modulation of hippocampal epileptic activity in vitro. PMID- 2575538 TI - Effects of chronic in vivo replacement of choline with a false cholinergic precursor. AB - Chronic administration to rats of a diet in which all choline is replaced by NADe, an unnatural choline analog, results in a classical hypocholinergic syndrome characterized by progressive loss of learning and memory, hyperkinesis, hyperreactivity and hyperalgesia. Discontinuation of the artificial diet results in rapid elimination of NADe from both free and phospholipid-bound pools in all tissues studied, but the behavioral effects recede more slowly and incompletely. These results are consistent with a model in which choline and NADe compete in both acetylcholine and phospholipid synthesis, resulting in selective vulnerability of cholinergic neurons. Histological studies are in progress to determine whether microanatomical changes are also consistent with this model. PMID- 2575536 TI - Actions of excitatory amino acid antagonists on synaptic potentials of layer II/III neurons of the cat's visual cortex. AB - Actions of excitatory amino acid (EAA) antagonists on the responses of cells in layers II/III and IV of the cat's visual cortex to stimulation of layer VI and the underlying white matter were studied in slice preparations. Antagonists used were 2-amino-5-phosphonovalerate (APV), a selective antagonist for the N-methyl-D aspartate (NMDA) type of EAA receptors, and kynurenate, a broad-spectrum antagonist for the three types of EAA receptors. In extracellular recordings it was demonstrated that most of the layer II/III cells were sensitive to APV, while the great majority of the layer IV cells were not. By contrast, kynurenate suppressed the responses completely in both layers. Excitatory post-synaptic potentials (EPSPs) evoked by stimulation of layer VI and the while matter were recorded intracellularly from layer II/III neurons. To determine whether the EPSPs were elicited mono- or polysynaptically, the synaptic delay for each EPSP was calculated from a pair of onset latencies of EPSPs evoked by stimulation of the two sites. Forty-two percent of the layer II/III cells were classified as having monosynaptic EPSPs. In 60% of these monosynaptic cells, the rising slope of the EPSPs was reduced by APV while in the other 40%, it was not. In the former (APV-sensitive cells), subtraction of the APV-sensitive component from the total EPSP indicated that the onset latency of the NMDA receptor-mediated component was roughly equal to that of the non-NMDA component. In the latter (APV-resistant cells), only the slowly-decaying component was in part mediated by NMDA receptors. The conduction velocities of the afferent fibers innervating APV resistant cells were slower than those of the APV-sensitive cells, suggesting that both types of cells are innervated by different types of afferents. The polysynaptic EPSPs of almost all layer II/III cells were sensitive to APV. The subtraction method indicated that the NMDA component had about the same magnitude as the non-NMDA components. When the slices were superfused by a Mg2+-free solution, the EPSPs were potentiated dramatically, but this potentiation was reduced to the control level during the administration of APV. Similarly, APV sensitive components were potentiated during the administration of bicuculline, a selective antagonist for gamma-aminobutyric acid receptors of A type. These results suggest that NMDA receptors participate, at varying degrees, in excitatory synaptic transmission at most layer II/III cells in the cat's visual cortex, and their actions appear to be regulated by intracortical inhibition. PMID- 2575540 TI - [Diurnal changes in the effectiveness of mental activity of the operators during shift-type work]. AB - Significant variations in the efficiency of the mental activities during the day are not detected at the shift operative work according to the average-group data. Significant differences are detected for 15% of the investigated at the level of P greater than 95%, for 45%--at the level of 80 less than P less than 95%. Significant differences within the mental activity indices under the given conditions are estimated as a decrease of adaptability of the organism. PMID- 2575539 TI - [Insulin and the central nervous system]. AB - Data from literature concerning the neurobiological, electrical and metabolic effects of insulin are reviewed. Emphasis is laid on insulin distribution in the CNS, on distribution and localization of the insulin brain receptors, on insulin transport through the hemato-encephalic barrier. Data concerning insulin effect on the electrical activity of various CNS neurons, particularly, on those of the feeding and satiety centres. The effects of insulin on the brain metabolism are discussed. Insulin shares many properties with the nerve growth factor and may be considered as specific neurotransmitter and neuromodulator. PMID- 2575541 TI - [Local neuroendocrine regulation of the cerebral vessels in acute disorders of cerebral blood circulation]. AB - The functional condition of lateral endocrine (melanocytes, mast cells) and neurogenic (adrenergic plexus) arterial apparatus of the cat brain during occlusion of the right common carotid artery for 5, 20, 35 min, was studied. The maximal decrease of the melanocytes occurred on the 20th min in the vessels of the right side of the Willis circle. An increased concentration of the mast cells and nervous fibers was found on the 20th min followed by its reduction by the 35th min on the side of ischemia. The reaction of the blood supply was evident as a gradual increase of the mast cells, longitudinal and transversal adrenergic fibers on the 35th min of the experiment. PMID- 2575542 TI - [The effect of prostacyclin on hemodynamics in blockade of the adreno- and M cholinoreactive structures]. AB - The alpha- and beta-adrenoceptors were found to strengthen a depressor effect of prostacyclin and to increase the heart rate in dogs. The blockade of M cholinoreactive structures increased the systolic volume alone. PMID- 2575543 TI - [The behavior of dipeptidyl peptidase IV in PUVA therapy of patients with psoriasis]. PMID- 2575544 TI - Collagen cross-linking. PMID- 2575545 TI - Modification of ornithine decarboxylase activity by adrenergic stimulation in cultured chicken spleen cells. AB - 1. In vivo, adrenergic agonists promote an increase of ornithine decarboxylase activity (ODC) in chicken spleen, as opposed to a decrease in thymus and bursa of Fabricius. The increase is not due to the cell fraction separated on Lymphoprep, i.e. the spleen cells, but it could be due to the macrophages. 2. With spleen cells in culture, a marked increase of ODC activity is observed during the first 3 hr, followed by a decrease. 3. cAMP drastically decreases after 10 min in culture. 4. Adrenergic agonists promote a decrease of activity, both alpha and beta receptors being involved in these modifications. TPA promotes partial desensitization. 5. Selenite, which in vivo has the same effect as epinephrine, enhances ODC activity in culture. Propranolol partially counteracts this effect, while prazosin has a synergistic effect. TPA partially desensitizes spleen cells to selenite. PMID- 2575546 TI - Regulation of particulate guanylate cyclase by Escherichia coli heat-stable enterotoxin: receptor binding and enzyme kinetics. AB - 1. Escherichia coli heat-stable enterotoxin (ST) induces a secretory diarrhea by binding to receptors on brush borders of intestinal villus cells, activating particulate guanylate cyclase and increasing intracellular concentrations of guanosine 3',5'-cyclic monophosphate (cyclic GMP). 2. However, little is known concerning coupling of receptor-ligand interaction to enzyme activation. 3. This study compares the kinetics of toxin-receptor binding and enzyme activation to better understand this transmembrane signal cascade. 4. Toxin receptor binding was linear and saturable with 50% of maximum displacement of [125I]ST by unlabeled toxin observed at 1.1 x 10(-7) M. ST increased the maximum velocity (Vmax) of guanylate cyclase with magnesium or manganese as the cation substrate without altering the affinity of the enzyme for its substrate or its positive cooperativity. 5. The concentration of toxin yielding half-maximum stimulation of guanylate cyclase was 1.2 x 10(-6) M, 10-fold higher than the affinity of the ligand for its receptor. 6. These data are consistent with the suggestion that ST receptor interaction is coupled to activation of particulate guanylate cyclase. 7. However, the discrepancy between the affinity of ST for its receptor and its efficacy in activating the enzyme suggests that this coupling is complex. 8. Possible mechanisms underlying this coupling are discussed. PMID- 2575548 TI - Pancreatic D-cell disorder in coxsackievirus B4-induced diabetic mice. AB - Pancreatic D-cell disorder was analyzed in Coxsackievirus B4-induced diabetic mice employing molecular hybridization with a radiolabelled probe to quantitate somatostatin mRNA, and specific immunoprecipitation to measure somatostatin synthesis and its release. Many infected mice showed blood glucose lower than noninfected control animals at 72 h postinfection and 85% became hyperglycemic at 6-8 weeks postinfection. Pancreatic somatostatin decreased by 24% and 43% at 72 h and 6 weeks postinfection, respectively, while somatostatin release in islets from the infected mice increased by 2-fold or more. Residual islet somatostatin content after release was initially higher than control at 72 h and then declined at 6 weeks. Islet cellular RNA content decreased by 35% at 6 weeks, somatostatin mRNA content decreased by approximately 45% at 72 h and 6 weeks postinfection. D cell disorder - somatostatin mRNA supply, synthesis, and release - is clearly evident in this model, which could be of significance in type I diabetes. PMID- 2575547 TI - Dopamine D2-receptor messenger RNA is differentially regulated by dopaminergic agents in rat anterior and neurointermediate pituitary. AB - Hypothalamic dopamine (DA), acting at DA D2-receptors (D2-R) on pituitary target cells, mediates peptide release and biosynthesis of rat pituitary anterior lobe (AL) prolactin, and neurointermediate lobe (NIL) pro-opiomelanocortin (POMC). We were interested in determining if dopamine agonists and antagonists were capable of modifying D2-R gene expression in these pituitary cells. Utilizing the recently published sequence of the rat D2-R, we isolated a rat D2-R cDNA clone by polymerase chain reaction, and have synthesized RNA probes to quantitate levels of D2-R mRNA by solution hybridization/nuclease protection assay. We report here that 5-day administration of the DA antagonist haloperidol led to significant increases in both D2-R mRNA and POMC mRNA in the NIL; the DA agonist bromocriptine caused a significant decrease in NIL POMC mRNA with no parallel change in D2-R mRNA. In contrast, no significant changes in D2-R mRNA in AL were observed following treatment with either the DA agonist or antagonist. These data provide evidence for tissue-specific regulation of D2-R mRNA in response to dopaminergic manipulation. PMID- 2575549 TI - Hormonal and paracrine regulation of gamma-glutamyl transpeptidase in rat Sertoli cells. AB - The effects of follicle-stimulating hormone (FSH) and testosterone on Sertoli cell gamma-glutamyl transpeptidase (gamma-GTP) activity have been studied in vitro. Addition of FSH to Sertoli cell cultures for 5 days induced stimulation of gamma-GTP activity. No testosterone effect was observed alone or in combination with different doses of FSH. Time course studies for a supramaximal dose of FSH showed that enzyme induction could be achieved after a 48 h stimulation. Furthermore, a gradual stimulation of gamma-GTP activity in response to increasing numbers of germinal cells (GC) added in coculture, was observed. Stimulation was also demonstrated with germinal cell-conditioned medium (GCCM). Stimulatory effects of GC and GCCM were additive with those of FSH, suggesting that different mechanisms were involved. PMID- 2575550 TI - Clinical, controlled trial of somatostatin with ranitidine and placebo in the control of peptic hemorrhage of the upper gastrointestinal tract. AB - There are many controversies concerning the treatment of hemorrhages of the upper gastrointestinal tract. In order to determine whether some currently used drugs, such as somatostatin (SST) and ranitidine, may be useful in the control of hemorrhages, we have conducted a controlled (not blind) study with alternate assignment in 220 accurately selected patients affected with hemorrhage secondary to acute peptic ulcer disease. We divided the patients into three groups on the basis of the severity of disease (moderate, serious, massive); a subgroup of each group underwent one of the three studied treatments (SST, ranitidine, placebo). After careful clinical and laboratory assessment, we followed the patients over a period of 72 h. The criteria to assess the efficacy of the treatment were: number of patients who had stopped bleeding; time needed to stop the hemorrhage, and the number of recurrences of bleeding in every group and subgroup. At the end of the study, SST and ranitidine were more effective in the control of hemorrhage than placebo. SST was more effective than ranitidine, especially in patients with moderate and serious hemorrhages; it achieved a recovery of nearly 100% in the group with moderate bleeding. PMID- 2575551 TI - Comparison of telenzepine, pirenzepine and atropine on gastric acid and pepsin secretion in response to histamine, pentagastrin, bethanechol, sham-feeding and feeding. AB - This study was designed to compare gastric antisecretory effects of telenzepine, a new antimuscarinic agent, with those of pirenzepine and atropine in dogs. None of these antimuscarinics affected gastric acid secretion induced by histamine but all of them caused a dose-dependent inhibition of acid secretion from the gastric fistula (GF) and Heidenhain pouches (HP) stimulated by pentagastrin and bethanechol, telenzepine being 5-9 times more potent than pirenzepine and equipotent with atropine. All antimuscarinics were also effective inhibitors of acid responses to sham feeding and ordinary feeding. The inhibitory effect of telenzepine and pirenzepine were not accompanied by any major alterations in plasma gastrin or somatostatin but those of atropine were related to significant increase in plasma gastrin and to significant decrease in plasma somatostatin levels, suggesting the involvement of M2 receptors in the cholinergic control of these hormones. All three antimuscarinics were effective inhibitors of pepsin secretion induced both from the GF and HP by all secretagogues used. Neither telenzepine nor pirenzepine administered in various doses affected the heart rate while atropine caused a significant increase in heart rate confirming that the former agents are selective M1 receptor antagonists. This study provides evidence that telenzepine is more potent than pirenzepine in the inhibition of gastric secretion induced by pentagastrin, bethanechol, sham-feeding and ordinary feeding and that, unlike atropine, it does not increase plasma gastrin responses to meat feeding. In fact, telenzepine and pirenzepine alike reduced plasma gastrin concentrations under these conditions. No influence of these antimuscarinics on plasma somatostatin levels was observed. PMID- 2575552 TI - Anterior boundaries of Hox gene expression in mesoderm-derived structures correlate with the linear gene order along the chromosome. AB - The developmental expression patterns of four genes, Hox 1.1, Hox 1.2, Hox 1.3 and Hox 3.1, were examined by in situ hybridization to serial embryonic sections. The three genes of the Hox 1 cluster, used in this study, map to adjacent positions along chromosome 6, whereas the Hox 3.1 gene maps to the Hox 3 cluster on chromosome 15. The anterior expression limits in segmented mesoderm varied among the four genes examined. Interestingly, a linear correlation exists between the position of the gene along the chromosome and the extent of anterior expression. Genes that are expressed more posterior are also more restricted in their expression in other mesoderm-derived tissues. The order of expression anterior to posterior was determined as: Hox 1.3, Hox 1.2, Hox 1.1 and Hox 3.1. Similarly, genes of the Drosophila Antennapedia and Bithorax complex specifying segment identity also exhibit anterior expression boundaries that correlate with gene position. The data suggest that Hox genes may specify positional information along the anterior-posterior axis during the formation of the body plan. PMID- 2575553 TI - Immunohistochemical analysis of stratum corneum components in oral squamous epithelia. AB - The generation of a stratum corneum in squamous epithelia involves marked changes in morphology and in the expression of cell products. We have examined the expression of some of the components involved in this process in oral squamous epithelia with different terminal differentiation patterns by use of immunofluorescent techniques. Involucrin and transglutaminase are involved in formation of cornified envelopes consistently seen in the stratum corneum. Both components were present in keratinized oral epithelia (palatal epithelium and hyperkeratinized buccal epithelium). The nonkeratinized normal buccal epithelium stained positive as well. Filaggrin, a protein derived from a precursor present in keratohyalin granules, is proposed to aggregate keratin filaments in the cornified layer. Although the staining differed markedly in quantity, this component was likewise detected in both keratinized and nonkeratinized epithelia. The staining patterns for different keratin polypeptides, however, showed qualitative differences between the different epithelia. Thus, it seems that the keratin composition shows differentiation-specific characteristics, whereas the presence of other important components needed to generate a stratum corneum is not as closely related to the terminal differentiation pattern of oral epithelia. PMID- 2575554 TI - Systemic effect of ipecac on acute toxicity of phenobarbital and theophylline in rats. AB - The emetic agent ipecac is widely used for the initial treatment of acute oral drug overdose. Its emetic and gastric evacuative efficacies have been studied extensively but its potential for pharmacologic interactions with various drugs and other possible poisons has not been explored. The purpose of this investigation was to determine if ipecac can alter the acute toxicity of two widely used drugs that act on the central nervous system, phenobarbital and theophylline. Ipecac syrup, 5 ml/kg, was administered by gavage to male Lewis rats either 1 hr before or 15 or 30 min after the start of an iv infusion of phenobarbital or theophylline. Control animals received the syrup vehicle only. Ipecac elicited vomiting-like behavior (frequent, wide opening of the mouth) for more than 1 hr. The drug infusion was stopped immediately after onset of the loss of righting reflex (phenobarbital) or maximal seizures (theophylline). Samples of cerebrospinal fluid, blood (for serum), and the brain were obtained at that time for analysis of drug concentrations. There were no significant differences between control and ipecac-treated animals with respect to the dose requirements and drug concentrations in cerebrospinal fluid, serum, and brain at the respective pharmacologic endpoint. It is concluded that ipecac has no apparent effect on the acute toxicity of phenobarbital and theophylline in rats. PMID- 2575555 TI - [Beta1- and beta2-adrenergic effects on thrombocytopoiesis in rats]. AB - The influence of beta 1- and beta 2-adrenergic agent injections to rats during 3 days, on the main parameters of thrombocytopoiesis: platelet number and per cent of build up 75seleno-methionine in newly-formed platelets of rats has been studied. It is established that beta 1-adreno-stimulation with dobutamine (DB) increases both the number of platelets and the per cent of build up isotope. Practolol (PC), a beta 1-adrenergic blocking agent, used separately, and combined application of PC + DB lowered significantly the parameters studied. Salbutamol stimulation of beta 2-adrenergic receptors induced an insignificant rise in the thrombocytopoiesis parameters. beta 1-adreno-stimulation with DB results in activation, while beta 1-adrenoblocking with PC--in suppression of thrombocytopoiesis. Pretreatment with PC prevents DB stimulating effect on thrombocytopoiesis, thus evidencing the beta 1-adrenoceptor dependence on the process. PMID- 2575556 TI - Recognition of Fusobacterium nucleatum subgroups Fn-1, Fn-2 and Fn-3 by ribosomal RNA gene restriction patterns. AB - DNA from representative strains of Fusobacterium nucleatum subgroups Fn-1, Fn-2 and Fn-3 was digested with restriction enzymes EcoRI and TaqI and the electrophoretically separated fragments hybridized with a 32P-16S rRNA gene probe from E. coli. The rRNA gene restriction patterns from DNA digested with either enzyme allowed the clustering of strains into the three subgroups. However, TaqI digested DNA yielded a wider distribution of taxonomically useful bands (ca 0.65 +/- 14.3 kbp) and the pattern produced was characteristic of each subgroup. The present method is a simple and reliable means of identifying the three subgroups of F. nucleatum and provides a useful method for further studies of the heterogeneity of F. nucleatum. PMID- 2575557 TI - Genetic analysis of prototrophic natural variants of Candida albicans. AB - To facilitate genetic analysis of Candida albicans natural variants, we have isolated a dominant mycophenolic acid-resistant mutant. Mycophenolic acid resistant auxotrophs were used to analyze prototrophic natural variants by spheroplast fusion. The fusion products were shown to be heterozygous for many of the parental chromosomes by molecular and genetic criteria. Using this approach, we have found that one type of morphologic variation is due to a recessive change and identified three dominant 5-fluorocytosine-resistant mutants. Rare fusion products express recessive parental markers. These exceptional progeny should be useful for linkage analysis and strain construction. PMID- 2575558 TI - Two TFIIIA activities regulate expression of the Xenopus 5S RNA gene families. AB - Immunoblotting experiments with polyclonal and monoclonal anti-transcription factor IIIA (TFIIIA) antibodies reveal different electrophoretic forms of TFIIIA in extracts from immature and mature oocytes of Xenopus laevis. The well characterized 39-kD TFIIIA species is present in approximately 10(12) copies per cell in stage I-III previtellogenic oocytes and declines in abundance by 10- to 20-fold during oogenesis. An immunologically related protein of apparent molecular mass of 42 kD is present at 2-4% of the level of 39-kD TFIIIA in immature oocytes, and the level of this protein increases dramatically during oogenesis. Both the 39- and 42-kD proteins are complexed with 5S RNA in 7S ribonucleoprotein (RNP) particles. High-level transcription of the oocyte-type 5S genes in vitro requires 39-kD immature oocyte TFIIIA, whereas both 39-kD TFIIIA and the mature oocyte TFIIIA species of 42 kD support somatic-type 5S transcription. TFIIIA of 42 kD does not support oocyte-type 5S transcription in a fractionated transcription system derived from mature oocytes. Both proteins, however, bind the oocyte-type and somatic-type genes with comparable affinities and exhibit similar DNase footprints on both genes. These results suggest a model for the developmental regulation of 5S RNA gene transcription where 42-kD TFIIIA serves as an activator of somatic-type 5S transcription and as a repressor of oocyte-type transcription during early embryogenesis. PMID- 2575559 TI - Cloning and characterization of the yeast chaperonin HSP60 gene. AB - The heat-shock protein, HSP60, is abundant in prokaryotes and eukaryotes and is required in the assembly of specific proteins. We have cloned the Saccharomyces cerevisiae HSP60 gene from a lambda gt11 genomic library using monoclonal antibodies, have obtained its sequence, determined its transcription start point, and shown that it exists as a single copy. The predicted HSP60 contains a mitochondrial target sequence and exhibits striking amino acid sequence similarity to its counterparts in bacteria, plants, and humans. These data indicate a high level of evolutionary conservation and are consistent with the suggestion of evolutionarily conserved function [Hemmingsen et al., Nature 333 (1988), 330-334]. PMID- 2575560 TI - A new vector using the human multidrug resistance gene as a selectable marker enables overexpression of foreign genes in eukaryotic cells. AB - A new vector, pSK1.MDR, has been constructed for expressing nonselectable genes in eukaryotic cells. The vector uses the human multidrug resistance gene, MDR1, as a dominant selectable marker and contains an additional transcription unit plus a unique SalI cloning site for inserting nucleotide sequences to be expressed. To test this expression system, a cDNA (IL2R) for the 55-kDa interleukin-2 receptor was inserted into the SalI site, and the resulting plasmid was transfected into NIH3T3 cells. Cells which acquired the MDR1 gene were selected with colchicine, and cells with high levels of MDR1 expression were selected by growth in increasing concentrations of the drug. Drug resistant cells also expressed the cotransferred, nonselected IL2R gene, and its expression was increased to 740,000 receptors per cell by growing cells in high concentrations of colchicine. The MDR1 system represents a very efficient method for synthesizing large amounts of protein in a wide variety of eukaryotic cells. PMID- 2575561 TI - Ascorbate activates soluble guanylate cyclase via H2O2-metabolism by catalase. AB - Conditions necessary for the activation by ascorbic acid of soluble guanylate cyclase purified from bovine lung have been examined. Ascorbic acid (0.1-10 mM) did not directly activate the enzyme, nonetheless, pronounced activation by ascorbate (3-10 mM) was observed in incubation mixtures containing 1 microM bovine liver catalase. Superoxide dismutase (SOD) and mannitol did not affect the catalase-dependent activation of guanylate cyclase elicited by ascorbate, suggesting that superoxide anion and hydroxyl radical were not mediating the activation of the enzyme. However, SOD enhanced the relatively low level activation of the enzyme elicited by catalase in the absence of added ascorbate. Pronounced inhibition (both with and without added ascorbate) was observed of catalase-dependent activation of guanylate cyclase by either ethanol (100 mM) or a fungal catalase preparation. Neither ethanol nor fungal catalase inhibited activation of guanylate cyclase by S-nitrosyl-N-acetyl-penicillamine (SNAP), a source of the nitric oxide free radical. These observations indicate that autoxidation of ascorbic acid or thiols present with the guanylate cyclase preparation leads to generation of H2O2, and its metabolism by bovine liver catalase mediates the concomitant activation of guanylate cyclase. The mechanism of activation appears to be associated with the presence of Compound I of catalase and to be inhibited by superoxide anion. PMID- 2575562 TI - [New developments in tocolysis]. PMID- 2575563 TI - [Prenatal diagnosis]. PMID- 2575564 TI - [Serotonin and blood pressure regulation--antihypertensive mechanism of ketanserin]. AB - The role of serotonin (5-HT) in blood pressure (BP) regulation was reviewed. Central and peripheral 5-HT receptors can be divided into three receptor subtypes: 5-HT1 (5-HT1A, 5-HT1B, 5-HT1C), 5-HT2 and 5-HT3 receptors. The selective agonists and antagonists of these receptor subtypes are useful for investigating the BP regulation by 5-HT. The central 5-HT1A receptor agonist 8 hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) produced hypotension and decreases in sympathetic nerve activity (SNA). This suggests that central 5-HT may cause decreases in both BP and SNA via 5-HT1A receptors. Since the 5-HT2 receptor antagonist ketanserin, which has an antihypertensive effect, decreased SNA and the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) increased SNA, central 5-HT2 receptors may be connected with the 5-HT-induced increases in both BP and SNA. On the other hand, ketanserin's antihypertensive effects via its 5-HT2 receptor blocking action in the vascular system indicates that peripheral 5-HT may contribute to the initiation or the maintenance of elevated vascular resistance in several forms of hypertension including essential hypertension. However, ketanserin also possesses alpha 1-adrenoceptor blocking action, and its precise antihypertensive mechanism has not been established. Further study of the antihypertensive mechanism of ketanserin will help clarify the precise role of 5-HT in BP regulation. PMID- 2575565 TI - [Non-adrenergic, non-cholinergic inhibitory innervation to the gastrointestinal tract]. AB - The smooth muscles of the gastrointestinal tract and blood vessels are innervated by non-adrenergic, non-cholinergic (NANC) inhibitory neurons. The transmitter(s) in relation to NANC inhibitory neurons remains unknown, but there are two main working hypotheses, the purinergic and VIPergic nerve hypotheses, at present. Although there is a large amount of data supporting the purinergic hypothesis, definitive evidence is still lacking. VIP seems to be regarded as a likely candidate for the neurotransmitters of some NANC inhibitory neurons. However, the data presented are still incomplete. For the purinergic hypothesis, the discrepancies seem to be greater in the stomach and oesophagus and those for the VIPergic hypothesis, in the guinea pig taenia coli. Moreover, there are many examples of the co-existence of peptides or of peptides and synthesizing enzymes of amines or acetylcholine in the gastrointestinal tract. Therefore, it is possible that NANC inhibitory neurons liberate more than one active inhibitory substance and/or there are different types of NANC inhibitory neurons in the gastrointestinal tract. Much more evidence seem to be needed before the neurotransmitter(s) of NANC inhibitory neurons in the gastrointestinal tract and blood vessels can be identified. PMID- 2575567 TI - [Materials science studies on the soldering of different orthodontic wires]. AB - In orthodontic technique both soldering and welding are standard methods for the application of auxiliaries and for the modification of force systems by joining wires of different cross-sections. Two cobalt-chromium alloys (Blue Elgiloy, Crozat) and an austenitic stainless steel alloy (Remanium) were soldered by an electrochemically generated hydrogen-oxygen flame forming an overlapped joint design. For characterization of the soldered joint testing procedures included microhardness tests, metallographic examination, tension-shear tests and surface analysis of the fractured joints by scanning electron microscopy. For any given soldering technique with an overlapped joint design the correct joint length is determined by the ratio t/s = 3 (t = overlapped length; s = diameter of the smaller wire). PMID- 2575566 TI - [Neuroleptic properties of Y-20024, a new benzofurancarboxamide derivative]. AB - N-[(1-butyl-2-pyrrolidinyl)methyl]-2-methyl-5-sulfamoyl-2,3- dihydrobenzofuran-7 carboxamide hydrochloride (Y-20024) was synthesized in our laboratories in anticipation of developing a new psychotropic drug. In the present study, the pharmacological properties of Y-20024 were compared with those of sulpiride (SPR) and haloperidol (HPD). Administered orally, Y-20024 was 10 times stronger than SPR in inhibiting apomorphine (0.5 mg/kg, s.c.)-induced hyperactivity in mice; administered intravenously or intracerebroventricularly, it was 2 times or one third as strong, respectively. Y-20024 was almost equipotent to SPR in antagonizing apomorphine (0.1 mg/kg, s.c.)-induced vomiting in dogs. Combined with methamphetamine (5 mg/kg, i.p.), Y-20024 and SPR induced mortality dose dependently in rats, but HPD did not. The mammotropic activity of Y-20024 administered orally once a day for 5 days was almost equipotent to that of SPR. From these results, Y-20024, pharmacologically similar to SPR, but superior in bioavailability and penetration through the blood brain barrier, may have potential usefulness as an antipsychotic drug. PMID- 2575568 TI - [Anterior tooth injury/anterior tooth loss--the epidemiological and orthodontic aspects]. AB - Trauma to incisors, especially loss of permanent anterior teeth, often effects aesthetics, function, psychology and phonetics. The following article describes the frequency, cause and effect of incisors lost as a result of the trauma. The treatment possibilities are discussed with respect to the specific orthodontic considerations. In addition, the indications for space closure by orthodontic or prosthetic procedures are discussed. PMID- 2575569 TI - SK&F 89124, a potent and selective agonist at prejunctional dopamine receptors. AB - SK&F 89124 (4-[2-(N,N-di-n-propylamino)ethyl]-7-hydroxy-2(3H) indolone) can be considered as a derivative of N,N-di-n-propyldopamine (DPDA) in which the meta hydroxyl is replaced by a cyclic amide function. SK&F 89124 is at least one order of magnitude more potent than DPDA as an agonist at peripheral inhibitory prejunctional dopamine receptors (DA2 receptors) in the isolated perfused rabbit ear artery. A potent agonist action of SK&F 89124 at the DA2 receptor can also be demonstrated by inhibition of radioactive overflow from prelabelled canine coronary artery or saphenous vein, and in the anesthetized dog as an inhibition of the tachycardia induced by cardioaccelerator nerve stimulation or the increase in hind-limb perfusion pressure induced by stimulation of the lumbar sympathetic chain. SK&F 89124 is a potent inhibitor of the binding of [3H]spiroperidol to D2 receptors in bovine pituitary homogenates. High concentrations of SK&F 89124 do not activate the adenylate cyclase D1 receptor in rat caudate homogenates, nor produce activation of alpha 2-adrenoceptors or H2-histamine receptors in the guinea pig atrium. Although some alpha 1-adrenoceptor mediated vasoconstriction is produced in the rabbit ear artery and rabbit aorta, the concentrations required are several orders of magnitude higher than those active at the DA2 receptor. From these data it is evident that this structural modification can increase both the potency and selectivity of DPDA as a DA2 receptor agonist. The potency and selectivity of SK&F 89124 make this agent a useful tool for determination of the functional role of the DA2 receptor. PMID- 2575570 TI - Effect of apomorphine on adrenal medullary catecholamine levels. AB - The effects of the dopamine receptor agonist, apomorphine, on the total catecholamine content of the adrenal medulla were studied in normotensive rats. Apomorphine (3, 15, 30 mg/kg SC) induced a dose-dependent decrease in catecholamine content of the adrenal gland. The action of apomorphine was suppressed by previous treatment with the non specific dopamine receptor antagonist, haloperidol (9 mg/kg IP), or the D2 antagonist domperidone (2 mg/kg IP), but not by the D1 antagonist SCH 23390 (1 mg/kg IP). The apomorphine-induced decrease in adrenal catecholamine concentration was suppressed by denervation of the adrenal medulla, i.e. unilateral section of splanchnic fibers performed 5 days before. These results show that, under our experimental conditions, the effect of apomorphine is due to the activation of D2 dopamine receptors probably located on splanchnic nerve endings and suggest the existence of a peripheral D2 dopaminergic system which modulates adrenal medullary catecholamine content. PMID- 2575571 TI - The effect of an oral morning dose of nizatidine and ranitidine on gastric acid secretion in duodenal ulcer patients. AB - The aim of this study was to compare the inhibitory effect and duration of action of a new H2-antagonist, nizatidine (150 mg per os), with ranitidine (150 mg per os) in a group of 10 patients with healed duodenal ulcer. The total inhibitory effect on acid output observed under basal conditions (30 min), during pentagastrin stimulation (120 min) and after stimulation (60 min), is overlapping. However, nizatidine showed a more rapid inhibitory activity -80%, and 31% higher than ranitidine with regard to basal acid output and maximum acid output, during the first hour of stimulation. On the other hand, ranitidine has a more prolonged antisecretory action--more than 27% and 54%, respectively, with regard to maximum acid output during the second hour and the period after hormonal stimulation. Also, variations in pepsin and acid output resulted in overlapping. In conclusion, these results, explainable by the pharmacodynamic property of the two drugs, confirmed the excellent inhibitory capacity of nizatidine, and furnish another reason for its use in clinical practice. PMID- 2575572 TI - Somatostatin as adjuvant therapy in the management of obstructive ileus. AB - The adjuvant use of somatostatin in the clinical management of obstructive ileus was studied prospectively. Fifty-four consecutive patients suffering from total obstructive ileus were managed over a period of one year. A double-blind clinical trial involving the administration of somatostatin for two days was carried out. Twenty-seven non-selected patients received somatostatin, while the other twenty seven did not. Of the 27 patients who did not receive somatostatin, 12 (44%) were operated on, while only 6 (22%) of those who had received the agent required surgery. As little as 16% of the patients who received somatostatin pre operatively exhibited severe dilatation and necrosis of the intestine proximal to the area of destruction as compared with 83% of those patients who did not receive somatostatin before the operation. It was concluded that while the administration of somatostatin to patients suffering from obstructive ileus may not be directly related to a reduction in surgery, it does reduce the effects of intestinal dilatation on the healthy gut proximal to the area of destruction. PMID- 2575573 TI - Involvement of adrenergic mechanism in hyperglycemia due to SCN stimulation. AB - Previously we found that in rats, electrical stimulation of the suprachiasmatic nucleus (SCN) of the hypothalamus elicited hyperglycemia associated with hyperglucagonemia without immediate hyperinsulinemia. To clarify the mechanism of these responses, we examined the effects of blockers of the autonomic nervous system on these responses. Hexamethonium, a ganglion blocker, suppressed the hyperglycemic and hyperglucagonemic responses to electrical stimulation of the SCN. Both bunazosin, an alpha 1-adrenergic blocker, and yohimbin, an alpha 2 adrenergic blocker, increased the level of insulin before stimulation, but only the latter suppressed the hyperglycemic and hyperglucagonemic responses. Propranolol, a beta-adrenergic blocker, partially inhibited the responses. These findings suggest that alpha 2- and beta-adrenergic mechanisms are involved in the hyperglycemic and hyperglucagonemic responses to SCN stimulation. PMID- 2575574 TI - Plasma somatostatin and vasoactive intestinal polypeptide responses to an oral mixed test meal in obese patients. AB - Ten obese and 10 control subjects were studied in basal conditions and after ingestion of a standard mixed test meal. Blood glucose, insulin, somatostatin (SLI) and vasoactive intestinal polypeptide (VIP) concentrations were determined before and 30, 60, 90, 120, 180 and 240 min after the start of the meal. Basal SLI levels in the obese (14.4 +/- 0.7 ng/l) were not significantly different from those in the controls (15.5 +/- 0.8 ng/l), whereas after the meal a blunted secretory response was recorded. Baseline plasma VIP levels were higher in the obese (29.7 +/- 1.5 ng/l) than in the control subjects (19.8 +/- 1.3 ng/l) and, similarly to the controls, were unaffected by meal ingestion. Data suggest that in the course of obesity an enhanced VIP secretion in association with a diminished SLI responsiveness to meals occurs. PMID- 2575575 TI - Inhibition of basal insulin secretion induces insulin resistance in normal man: evidence for a tonic effect of insulin on carbohydrate metabolism. AB - Insulin resistance has been demonstrated both in insulin deficiency and insulin excess in man and in animals. This study was carried out in normal man to evaluate the role of insulinopenia in the pathogenesis of insulin resistance. Insulin suppression was obtained by 4 h somatostatin (SRIF) infusion. Insulin receptors on circulating monocytes were evaluated before and after SRIF infusion; an insulin tolerance test (ITT) was performed after SRIF, saline or SRIF and replacing basal insulin secretion. Insulin binding to circulating monocytes did not change after 4 h insulinopenia (2.19 +/- 0.30 vs. 2.35 +/- 0.80%), while insulin sensitivity appeared decreased after SRIF (KITT = 0.97 +/- 0.13) as compared with saline (KITT = 3.30 +/- 0.42), and this effect was prevented by insulin (KITT = 2.46 +/- 0.38). A relationship was detected between KITT and plasma insulin concentration before ITT (r = 0.85, p less than 0.01), suggesting that insulin deficiency is the main cause of the phenomenon observed. The present data suggest that basal insulin concentration plays an essential role in the control of insulin sensitivity. If insulin binding on monocytes mimics the behavior of major insulin target tissues, it is possible that the impaired insulin action after 4 h of insulin deficiency is related to a post binding effect. PMID- 2575576 TI - Involvement of central somatostatin in the alteration of GH secretion in starved rats. AB - In order to determine the central or peripheral origin of the starvation-induced modifications of growth hormone (GH) and thyroid-stimulating hormone (TSH) secretions, the effects of starvation were studied in freely moving male rats with hypothalamo-hypophyseal disconnection. Five days after the disconnection GH secretion exhibited lower maximal values and higher trough levels and ultradian pulsatile secretion was lost as compared to controls. TSH levels were also decreased. The lesion did not modify pituitary somatostatin (SRIF) receptors as assessed by 125I-Tyr-O-D-Trp-8-SRIF binding or inhibition of adenylate cyclase activity. On the other hand, the growth hormone releasing factor (GRF) capacity to stimulate adenylate cyclase was strongly reduced by the lesion without modification of the affinity. Exposure to 72 h food deprivation decreased GH pulses and TSH levels in control rats but did not modify GH secretory profiles or TSH levels of lesioned rats. Plasma glucose and insulin levels were equally decreased after fasting in control and lesioned rats. Altogether, our results demonstrate that starvation-induced modifications of GH and TSH secretions are of central origin while glucose and insulin changes are peripherally triggered. They suggest that the hypothalamus is the only source of SRIF implicated in this effect. PMID- 2575577 TI - Genetic screening of endocrine tumour syndromes with DNA probes: the example of medullary thyroid carcinoma. AB - Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal-dominant syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and parathyroid hyperplasia. Recent reports have assigned the locus of MEN2A to the pericentromeric region of chromosome 10. Through the 'Groupe d'Etude des Tumeurs a Calcitonine', we have evaluated the ability to predict the carrier state using DNA probes. Our results suggest that the restriction fragment length polymorphism method can be used to identify individuals at risk within MEN2A families. They may then be followed by conventional endocrine methods for the onset of neoplastic changes, limiting the risk of subsequent metastatic disease. The method also permits the exclusion of further screening for family members at very low risk. Extension of the screening program can now be anticipated for other inherited forms of MTC, such as familial MTC without pheochromocytoma or other endocrinological tumor syndromes such as MEN1 for which the locus has also recently been mapped. PMID- 2575578 TI - Multiple endocrine neoplasia type II: clinical, biological and epidemiological features. French Medullary Study Group. AB - Medullary thyroid carcinoma (MTC) is a particularly interesting model of gene expression in cancer. As a matter of fact, it is remarkable from many points of view: it occurs in two forms: (1) MTC only or part of a multiple endocrine neoplasia II (MEN II), and (2) it is sporadic or inherited and benefits from a specific and sensible marker, calcitonin; the gene responsible for the hereditary form is localized on chromosome 10. Taking into account clinical, biological, genealogical and epidemiological features of the disease as supporting one another, a French collective study has been initiated; preliminary analysis of data allows to conclude on the value of such national collaboration for early diagnosis, prognosis and estimation of the incidence of the disease. PMID- 2575579 TI - HPLC analysis of somatostatin peptides secreted by a rat pancreatic endocrine cell line (RINT3): stimulation studies. AB - A combination of anion exchange and reverse phase HPLC leading to the purification of a 15-kd proform of somatostatin from culture medium of the pancreatic tumoral endocrine RINT3 cell line is described. Elevation of extracellular calcium concentration causes a dose-dependent stimulation of somatostatin release; maximal stimulation (2.8-fold over basal) was reached with 5 mM Ca. Furthermore, 0.01 microM TPA induced a stimulation of about the same amplitude while forskolin had a low effect. These data suggest that secretion of somatostatin in this model can be regulated by the Ca/C protein-kinase pathway. PMID- 2575581 TI - Multilocus linkage analysis with the human argininosuccinate synthetase gene. AB - We have identified three restriction fragment length polymorphisms (RFLPs) from within the argininosuccinate synthetase (ASS) gene which maps to human chromosome 9q34-qter. Although RFLPs at pseudogene loci are detected by the cDNA, these are the first polymorphisms reported at the ASS locus. The three RFLPs are in linkage equilibrium with each other, and haplotypes for the ASS locus are highly informative. Two-locus recombination estimates between ASS and seven other 9q markers indicated that ASS is closest to the ABO blood group with a recombination fraction of 0.04 (0.005-0.11). A multilocus lod score analysis with these seven 9q markers indicated that ASS maps between ABL and MCT136 close to ABO, but it is uncertain if ASS is centromeric or telomeric to ABO. PMID- 2575580 TI - Transposition, amplification, and divergence in the origin of the DNF15 loci, a polymorphic repetitive sequence family on chromosomes 1 and 3. AB - The loci DNF15S1 and DNF15S2 are members of a small repetitive sequence family at discrete chromosomal locations, namely, 1p36 and 3p21, respectively. Studies of the structure, arrangement, and interrelations of the family suggest that the single copy on chromosome 3 is the original member and that this gave rise to the several members on chromosome 1 by transposition, partial duplication, and amplification. Several restriction fragment length polymorphisms have been discovered at the DNF15S1 locus and these have been assigned to the different subfamilies of the repeat at this locus. The existence of these RFLPs, and the nonallelic restriction site variation also found in this sequence family, suggests that transposition and amplification occurred as discrete events. We sequenced across the ancient junction between chromosomes 1 and 3 and noted features which might explain the mechanics of the transposition and amplification events. PMID- 2575582 TI - Level of expression and chromosome mapping of the mouse cholecystokinin gene: implications for murine models of genetic obesity. AB - Cholecystokinin (CCK) is a neuropeptide which is present in brain and intestine and which stimulates gall bladder contraction and pancreatic secretion. Additional studies have demonstrated an appetite-suppressing effect of CCK in vivo. These data have aroused speculation that the physiology of this hormone could be relevant in the pathogenesis of the mouse obesity mutations ob on chromosome 6 and db on chromosome 4. In order to determine whether abnormalities of this hormone could be the primary defect in these obesity mutations, we have used three separate approaches to map the mouse Cck gene to distal chromosome 9, where it is part of a syntenic group between mouse chromosome 9 and human chromosome 3. These data therefore exclude cholecystokinin as the etiologic factor in the pathogenesis of any of the known mouse obesity syndromes. In order to exclude the possibility that there are differences in mutant animals in the level of CCK RNA, we have used an S1 nuclease protection assay as well as a novel radioimmunoassay that detects the CCK precursor, to show that there are no gross differences in CCK mRNA or protein precursor levels between ob/ob and wild-type animals. PMID- 2575583 TI - Localization of the muscle, liver, and brain glycogen phosphorylase genes on linkage maps of mouse chromosomes 19, 12, and 2, respectively. AB - Mammalian glycogen phosphorylases comprise a family of three isozymes, muscle, liver, and brain, which are expressed selectively and to varying extents in a wide variety of cell types. To better understand the regulation of phosphorylase gene expression, we isolated partial cDNAs for all three isozymes from the rat and used these to map the corresponding genes in the mouse. Chromosome mapping was accomplished by comparing the segregation of phosphorylase restriction fragment length polymorphisms (RFLPs) with 16 reference loci in a multipoint interspecies backcross between Mus musculus domesticus and Mus spretus. The genes encoding muscle, liver, and brain phosphorylases (Pygm, Pygl, and Pygb) are assigned to mouse chromosomes 19, 12, and 2, respectively. Their location on separate chromosomes indicates that distinct cis-acting elements govern the differential expression of phosphorylase isozymes in various tissues. Our findings significantly extend the genetic maps of mouse chromosomes 2, 12, and 19 and can be used to define the location of phosphorylase genes in man more precisely. Finally, this analysis suggests that the previously mapped "muscle deficient" mutation in mouse, mdf, is closely linked to the muscle phosphorylase gene. However, muscle phosphorylase gene structure and expression appear to be unaltered in mdf/mdf mice, indicating that this mutation is not an animal model for the human genetic disorder McArdle's disease. PMID- 2575584 TI - The mouse neurological mutant weaver maps within the region of chromosome 16 that is homologous to human chromosome 21. AB - Utilizing the backcross C57BL/6 wv/wv x (C57BL/6 wv/wv x MOLD/Rk), the mouse neurological mutation weaver (wv) was mapped less than 1 cM proximal to Ets-2 and Mx on mouse chromosome 16 (0.96 +/- 0.1% recombination). This region is known to include eight genes that are found on human chromosome 21 (HSA 21) and appears to be highly conserved between the two species. We therefore predict that the normal human homolog of wv will be located on HSA 21 and would be in dosage imbalance in individuals with Down syndrome. PMID- 2575585 TI - Chromosome assignment of the murine Hox-4.1 gene. AB - The murine homebox gene 4.1 was assigned to chromosome 2 by Southern analysis of somatic cell hybrids and by in situ hybridization. This assignment and the report of Featherstone et al. (M. S. Featherstone, A. Baron, S. J. Gaunt, M. G. Mattei, and D. Duboule, 1988, Proc. Natl. Acad. Sci. USA, 85, 4760-4764) indicate that a fourth group of homeobox genes is located on chromosome 2 in the mouse (in addition to the homeobox gene clusters on chromosomes 6, 11, and 15). PMID- 2575586 TI - At least four different chromosomal regions are involved in loss of heterozygosity in human breast carcinoma. AB - Three chromosome regions, i.e., 11p15, 13q, and 17p, were previously reported by three independent groups to be specifically reduced to hemizygosity in human primary breast cancer. We examined the DNA of 64 mammary tumors for loss of heterozygosity (LOH) with 28 polymorphic DNA markers dispersed on 10 arms of 8 different chromosomes. Complete or near-complete absence of LOH was observed on 5 arms (5 chromosomes). LOH at all three previously invoked regions was confirmed, and the highest frequency was found on 17p (67% of heterozygous patients). Allele loss of a marker from chromosome 3 (region p14-p21) was found in 7 of 15 informative cases. Concurrent LOH at 2 to 4 loci was noted in 20 of the 43 tumors showing LOH. Allele losses did not correlate with any of the six clinico histopathological variables investigated, but in a group of patients in which we were unable to demonstrate LOH, the absence of distant metastases was statistically significant (P less than 0.05). These results suggest that some of the observed allele losses reflect random events, possibly as a result of genetic instability, but are not without biological significance for the progression of particular subclasses of breast tumors. PMID- 2575587 TI - Isolation of a novel mildly repetitive DNA sequence that is predominantly located at the terminus of the short arm of chromosome 4 near the Huntington disease gene. AB - A novel mildly repetitive DNA sequence that is reiterated approximately 20 times in the human genome has been isolated and characterized. Most of the repeat units are localized very near the terminus of the short arm of chromosome 4 (4p) in the region known to contain the Huntington disease (HD) gene. A cloned probe that detects the repeated sequence reveals a restriction fragment length polymorphism that is close to and/or distal to the most distal genetic locus on 4p. This probe, therefore, provides a new genetic marker very close to and possibly flanking the HD gene. In addition, this probe should prove very useful for detailed physical mapping of the most distal region of 4p around the HD gene. The few (two or three) copies of this repeat not located near the terminus of 4p are located near the ends of two other chromosomes, 14 and 21. PMID- 2575588 TI - A multipoint linkage map around the locus for myotonic dystrophy on chromosome 19. AB - Employing 16 polymorphic DNA markers as well as the chromosome 19 centromere heteromorphism, we have performed a genetic linkage study in 26 families with myotonic dystrophy. Fourteen of these markers had been assigned previously to one of five different intervals of the 19cen-19q13.2 segment by using somatic cell hybrids. For the long arm of chromosome 19, a genetic map that encompasses 9 polymorphic markers and the DM gene has been constructed. Our studies indicate that the DM and CKMM genes map distal to the ApoC2-ApoE gene cluster and to the anonymous polymorphic markers D19S15 and D19S16, but proximal to the D19S22 marker. The orientation of DM and CKMM remains to be determined. PMID- 2575589 TI - Mouse melanoma growth stimulatory activity gene (Mgsa) is polymorphic and syntenic with the W, patch, rumpwhite, and recessive spotting loci on chromosome 5. AB - Melanoma growth stimulatory activity (Mgsa) is a polypeptide growth factor originally detected in culture medium of the human malignant melanoma cell line Hs294T and may have an autocrine role in neoplastic growth. Mgsa is a member of the small inducible gene (SIG) family and shares homology with beta thromboglobulin and platelet factor 4. Mgsa was localized to chromosome 5 using a cDNA probe for mouse Mgsa and somatic cell hybrids and is thus syntenic with Kit (W), Ph, Rw, and rs loci. The results eliminate Mgsa as the product of the Steel locus on chromosome 10, but raise the possibility that Mgsa might be synonymous with a chromosome 5 locus affecting skin pigmentation. PMID- 2575590 TI - A PstI polymorphism for the human erythrocyte surface protein band 3 (EPB3) demonstrates close linkage of EPB3 to the nerve growth factor receptor. AB - Erythrocyte surface protein band 3 (EPB3) plays an important role in CO2 transport in the blood. We have isolated a recombinant lambda bacteriophage that contains coding sequence for the human gene. Sequence analysis demonstrated that the human insert contains a portion of exon 13. A 1.1-kb BamHI fragment revealed a two-allele polymorphism with PstI. Alleles of 1.4 and 0.9/0.5 kb were present in Caucasoids at frequencies of 0.74 and 0.26, respectively. EPB3 has previously been mapped to 17q21-qter by in situ hybridization, and linkage analysis showed that EPB3 is tightly linked to the gene for the nerve growth factor receptor (NGFR). The maximum likelihood estimate of recombination (theta) is 0.00, with a lod score of 11.40 and confidence interval of 0.00 to 0.04. PMID- 2575591 TI - Linkage genetics of mouse ornithine decarboxylase (Odc). AB - Ornithine decarboxylase (ODC) is synthesized as a single polypeptide in the mouse, but DNA sequences reactive with ODC cDNA probes have been mapped to multiple mouse chromosomes. A DNA fragment from the untranscribed 5' flank of a transcriptionally active ODC gene has been used as a probe to define a restriction fragment length polymorphism associated with the gene. The pattern of inheritance of this polymorphism in recombinant inbred strains of mice and in progeny of a conventional backcross localized it to proximal chromosome 12. This result confirms previous experiments with somatic cell hybrids that mapped the gene to chromosome 12 and further defines the linkage group conserved between proximal chromosome 12 and human chromosome 2p. The other ODC homologs are tentatively identified as cDNA-like pseudogenes. PMID- 2575592 TI - Linkage of the mouse LDL receptor gene on chromosome 9. AB - We identified restriction fragment length variants of the mouse low-density lipoprotein receptor gene and used these to map the gene, designated Ldlr, to the proximal region of chromosome 9. An interspecific backcross between strains MEV and CAST/Ei yielded the following gene order and distances in centimorgans: Ldlr 18.8 +/- 5.6-Apoa-4-7.3 +/- 3.5-Mpi-1-10.2 +/- 3.9-Emv-3 or dilute. Analysis of recombinant inbred strains also indicated that Ldlr is tightly linked to a previously unmapped retroviral marker, Xmmv-67. PMID- 2575593 TI - X-chromosomal DNA polymorphisms in two ethnic groups from India. AB - Four polymorphic sites of the short arm of the X chromosome were studied in two racial groups from India, the Assamese and the Malayalee. Since the allelic frequencies of the two groups did not differ markedly from each other, the data from the two populations were pooled. The frequency of the A2 allele was 0.57 for the L1.28 probe, 0.20 for the RC8 probe, 0.28 for the pD2 probe and 0.11 for the L754 probe. The A3 allelic fragment of the RC8 probe was not found among 67 Indians, and in one Assamese woman an additional 7.0-kilobase fragment was found. The differences between the Indian population and other ethnic groups were analyzed. PMID- 2575594 TI - Interzeta-globin gene hypervariable regions in Chinese: application to genetic diagnosis of adult polycystic kidney disease. AB - In order to investigate the interzeta-globin gene hypervariable regions (IZHVR) in Chinese, DNA samples from 114 unrelated normal individuals were analyzed using the restriction endonuclease BglII and hybridized with a 32P-labeled zeta-globin probe. Four polymorphic fragments containing IZHVR with different frequencies were found: 11.3 kb, 0.24; 10.8 kb, 0.50; 10.4 kb, 0.05, and 10.0 kb, 0.21. Using these polymorphic fragments as linkage markers, we were able to trace the affected siblings in a three-generation Chinese family with a history of adult polycystic kidney disease. PMID- 2575595 TI - X chromosome restriction fragment length polymorphisms in five racial groups: rare variant detected with the RC8 (DXS9) probe in the Marathi population, India. AB - Restriction fragment length polymorphisms were investigated in five racial groups using the X chromosome probes DXS9 and DXS7. The allele frequencies of these polymorphisms showed significant differences and both DNA fragments were found to be highly polymorphic in the populations of south and southeast Asia. In the Marathi population of India, a rare allele B*3 (3 kilobases; kb) and an altered 7 kb fragment instead of the 6.6-kb constant band were found with DXS9. This is the first time that the rare B*3 allele is found in a non-European population. PMID- 2575596 TI - Tissue-type plasminogen activator restriction fragment length polymorphism in the Chinese, Indians and Malays of Singapore. AB - A total of 215 subjects comprising 95 Chinese, 66 Malays and 54 Indians were investigated for restriction fragment length polymorphisms of the tissue-type plasminogen activator (PLAT) gene at an EcoRI site using the probe ptPA-4352. The phenotypic distribution showed a good agreement with the Hardy-Weinberg equilibrium. The gene frequencies of PLAT*1 were found to be 0.47 in the Chinese, 0.52 in the Malays and 0.41 in South Indians. PMID- 2575597 TI - Interleukin 2 production by alloantigen-stimulated CD4+ and CD8+ human T cell subsets: frequency of HLA class I or class II-reactive precursor cells and clonal specificity of activated T cells. AB - A recently developed limiting dilution (LD) method was used to analyze the frequency and specificity of IL2-producing cells within alloantigen-stimulated human CD4+ and CD8+ T cell subsets. Cell sorter-separated CD4+ and CD8+ responder cells were cocultured under LD conditions with HLA class I and/or class II different Epstein Barr virus (EBV)-transformed lymphoblastoid cells line (LCL) stimulator cells in the absence of additional factors. After 3 days, IL2 in cell free culture supernatants was measured by a colorimetric assay on IL2-dependent murine CTLL cells. Under these conditions, one out of 200-500 CD4+ and one out of 300 to 1000 C8+ T cells produced IL2 when stimulated by HLA class I and class II disparate LCL. By using selected responder and stimulator cells differing only in HLA class I (A, B, C) or class II (DR) antigens, it was found that CD4+ T cells produced IL2 in response to HLA class II antigens, while CD8+ T cells produced IL2 in response to HLA class I antigens. Surprisingly, high frequencies of IL2 secreting CD4+ T cells were noted in certain HLA-DR-identical responder stimulator combinations. To investigate whether HLA class II antigens other than DR (i.e., DQ or DP) activate CD4+ cells to IL2 secretion, we analyzed a set of HLA-A,B,C and -DR,DQ-identical responder-stimulator cells which differed only in DP antigens. In several of these instances, we measured high frequencies (f = 1/1000 to 1/2000) of HLA-DP-reactive CD4+ IL2 producers, while the frequencies in LD cultures stimulated with autologous LCL were low (f = 1/10,000 to 1/30,000). The specificity of alloantigen-activated IL2-secreting T cells was assayed by restimulation with the original or HLA-mismatched third-party LCLs. CD4+ responder cells could be efficiently and specifically restimulated to IL2 production after a resting period of 3 to 4 days, while CD8+ cells were refractory to restimulation under these conditions. Together these data demonstrate that: 1) CD4+ and CD8+ cells are stimulated to IL2 production by HLA class II and class I antigens, respectively; 2) alloantigen-activated CD4+ IL2 producers are highly specific for stimulating HLA antigens as shown by a split culture and restimulation approach; and 3) significant numbers of CD4+ IL2 producing T cells can be activated by selected HLA-DR-identical, DP-different stimulator cells. PMID- 2575598 TI - Coexistence of antigen-specific TH1 and TH2 cells in genetically susceptible BALB/c mice infected with Leishmania major. AB - CD4-positive T cell clones with specificity for the protozoan parasite Leishmania major (L. major) of both the protective TH1 and the disease-exacerbating TH2 subtype were isolated from a diseased L. major-infected mouse of the susceptible BALB/c strain. In addition, TH2 cells were isolated from the lesion-draining lymph nodes of an animal clinically healed nine months after sublethal irradiation and subsequent infection. Our data support the notion that the differential outcome of the disease in non-irradiated versus irradiated BALB/c mice reflects the regulation of the two CD4+ T cell subsets. These data also argue against the possibilities that: 1) TH2 cells and their precursors are totally eliminated by irradiation and that 2) TH2 cells are capable of completely hindering the expansion of TH1 cells in diseased animals. PMID- 2575600 TI - Role of peptide-leukotrienes in liver injury in mice. AB - The role of peptide leukotrienes (p-LTs), especially LTC4 and LTD4 in liver disease, was investigated in mice experimental liver injury models. The liver injury was induced by the injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum pretreated mice. Carbon tetrachloride (CCl4)-induced liver injury in mice was used as a standard model. In both injury models, extensive liver parenchymal cell damage was observed by the elevation of glutamate transaminase (GOT and GPT) activity and confirmed by significant histopathological changes in the liver. Moreover, significant elevation of LTC4 in the liver was observed in both models 1 and 6 h after the onset of disease. Administration of AA-861, a selective 5-lipoxygenase inhibitor (0.5, 1, and 2 mg/kg) and LY-171883, a p-LT receptor antagonist (50 and 200 mg/kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes in both experimental liver injury models. In addition, when authentic LTC4 or LTD4 was injected into the mouse, clear elevation of serum GOT and GPT and histopathological changes of the liver were observed. These results suggest that p-LTs play a role in the onset of liver diseases in mice. PMID- 2575599 TI - Variable stimulation of adenylate cyclase activity by vasoactive intestinal-like peptides and beta-adrenergic agonists in murine T cell lymphomas of immature, helper, and cytotoxic types. AB - We examined several cultured murine T cell lymphomas, induced by a radiation leukemia virus MuRadLV, including cell lines derived from immature T cells (5 clones of the BL/VL3 cell line), antigen-specific T helper cells (5 lines of the TL2 series), and one T cytotoxic cell line (NS8). With one exception (the TL2-9 cell line), these cells showed common characteristics: 1) an efficient adenylate cyclase system; 2) increased cyclic AMP production in response to at least one type of neurotransmitter, i.e., to the catecholamine isoproterenol and/or the neuropeptide VIP; 3) on the basis of adenylate cyclase stimulation, beta adrenoceptors were of the beta 2 subtype and VIP receptors were of a "helodermin preferring" subtype previously encountered in a human T lymphoblast cell line. Although we analyzed only a limited number of cell lines, it appeared that the immature T BL/VL3 clones responded to peptides of the VIP family with higher potency and efficacy than T helper and T cytotoxic cells. The membranes from the specific TL2-9 helper cell line were without adenylate cyclase activity in the presence of Gpp[NH]p, NaF, and GTP alone or GTP in the presence of isoproterenol or VIP. They produced cyclic AMP in the presence of Mn2+ and forskolin only, suggesting a defect in Gs as in S49 cyc- mouse lymphosarcoma cells. This was further demonstrated by the absence of cholera toxin-stimulated ADP-ribosylation in TL2-9 membranes. PMID- 2575601 TI - The gastroenteropancreatic endocrine system and related tumors. AB - Up to 16 types of endocrine cells have been characterized morphologically (and most of them also functionally) in the gastroenteropancreatic area. Four main groups of pancreatic endocrine tumors (with several subtypes) have been identified: islet cell, ectopic, nonfunctioning, and poorly differentiated tumors. A detailed classification system that combines cytologic and clinicopathologic patterns has been developed for the study of 132 pancreatic tumors. Among a large series (more than 120 cases) of endocrine tumors arising in the gastrointestinal tract, serotonin-producing argentaffin carcinoids have been separated from hindgut trabecular carcinoids, producing glucagon- and pancreatic polypeptide-related peptides, paragangliomas, somatostatin cell tumors, gastrinomas, and argyrophil ECL cell carcinoids. The clinicopathologic profile of the various pancreatic and gastrointestinal tumor entities has been delineated and involvement in the multiple endocrine neoplasia syndrome has been analyzed in detail. PMID- 2575602 TI - Recent advances in the management of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. AB - Several histamine H2 receptor antagonists and the H+,K(+)-ATPase inhibitor, omeprazole, have been shown to be capable of controlling gastric acid secretion safely and effectively in patients with Zollinger-Ellison syndrome. The relative merits of these agents are discussed, and their use in the acute and long-term control of acid hypersecretion and in special circumstances that require particular care are described. The surgical approaches to the control of acid secretion are described, and the current place of surgery in the management of acid hypersecretion is discussed. PMID- 2575603 TI - Immunosuppression and in vivo T cell function in granulomatous inflammation. AB - Subcutaneous grafts of fresh or freeze-dried hepatic schistosome egg granulomas in inbred mice caused increased numbers of total cells, T cell subsets, and elevated DNA synthesis in regional lymph nodes. This in vivo T cell activation was not apparent by in vitro tests. Spleen cells were unaffected both in vivo and in vitro. Immunosuppressive therapy with ciclosporin or monoclonal antibodies to T cell subsets profoundly depressed the T cell numbers and function, even when primed by a prior graft. Subsequent grafting partly reversed these effects, and T cells became activated. The findings indicate that in vitro assessment of activation and suppression of T cell function does not necessarily correspond to the events occurring in vivo. PMID- 2575604 TI - The effect of 2-acetyl-4-tetrahydroxybutylimidazole on lymphocyte subsets in peripheral blood of the rat. AB - A constituent of Ammonia Caramel, 2-acetyl-4-tetrahydroxybutylimidazole (THI), is known to cause a reduction in the number of circulating lymphocytes when fed to rats. In the present study the effect of giving THI 1 mg/kg by gavage daily for 7 days on the numbers of lymphocytes in subsets has been monitored in peripheral blood. Both immunoglobulin light chain-bearing B-cells (MARK-1+) and CD5 marker bearing T-cells (OX-19+) were reduced in number within 1 day of treatment. Within the pan-T-cell population, Class II MHC reactive helper T-lymphocytes (W3/25-) were more reduced than the Class I MHC reactive cytotoxic/suppressor T cells (OX 8+). The number of null cells (MARK-1-, OX-19-) was not affected; the majority of these cells appeared to be large granular lymphocytes. PMID- 2575605 TI - Synthesis and in vivo characterization of D-(+)-(N1-[11C]methyl)-2-Br-LSD: a radioligand for positron emission tomographic studies of serotonin 5-HT2 receptors. AB - D-(+)-N1-Methyl-2-Br-LSD (MBL), which displays high affinity and selectivity for serotonin receptors in vitro, has been labeled with carbon-11 for localization of cerebral serotonin 5-HT2 receptors by positron emission tomography. [11C]MBL was prepared from [11C]iodomethane and D-(+)-2-Br-LSD within 20 min from end of bombardment. The average specific activity of [11C]MBL was 2300 mCi/mumol and the average radiochemical yield was 17%, both at end of synthesis. The in vivo regional distribution of radioactivity in brain after i.v. administration of [11C]MBL to mice paralleled the known density of serotonin 5-HT2 receptors. The maximum specific binding, defined by a frontal cortex to cerebellum radioactivity concentration ratio of 5.4 to 1, was reached 30 min postinjection. Administration of ketanserin, a potent serotonin 5-HT2 receptor antagonist, markedly blocked radioligand binding in all brain regions examined except cerebellum. PMID- 2575606 TI - Variations of a Y chromosome repeated sequence across subspecies of Mus musculus. AB - The complex species Mus musculus is widespread in Eurasia and consists of four parapatric genetical entities (subspecies) that have recently radiated. Two of them (M. m. domesticus and M. m. musculus) are known to interact through a narrow zone of hybridisation across which autosomal and mitochondrial exchanges are very limited and Y chromosome exchange is absent. We extend here the study of this group by the genetical analysis of 22 Asian strains of various origins (China, Korea, Japan, Taiwan, Philippines and Indonesia). A survey of protein variation at ten polymorphic loci confirmed that these animals belong to either the subspecies M. m. musculus (northern type in Asia, ranging westwards to Eastern Europe) or to M. m. castaneus (southern Asian type) and revealed a certain degree of intergradation between the two taxa. Y chromosome variations were assessed in these strains using a Y specific DNA probe representing part of a small multigene family and also in four M. m. domesticus (the Western European house mouse) strains of various origins and one M. m. bactrianus (from Pakistan). Musculus and castaneus were identically monomorphic for one type of organisation of this Y repeated family, while domesticus and bactrianus were very similar to each other, showing slightly different types of organisation. Introgression of a bactrianus Y chromosome into the territory of castaneus was found in Indonesia. The present distribution of the Y types among the four subspecies is not phylogenetically concordant with the known distributions of autosomal and mitochondrial variants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575608 TI - Multidrug resistance in cultured human leukemia and lymphoma cell lines detected by a monoclonal antibody, MRK16. AB - Forty cultured human leukemia and lymphoma cell lines never exposed to anticancer agents in culture, apart from doxorubicin (ADM)-resistant K562/ADM, were examined for reactivity with a monoclonal antibody, MRK16 in F(ab')2 form [MRK16-F(ab')2], which recognizes P-glycoprotein (P-gp). The relative resistance index to various drugs was calculated by dividing the 50% growth inhibitory concentration (IC50) of the test cell line by IC50 of K562, which was the negative control in the antibody experiment. MRK16-F(ab')2 reacted with four cell lines, K562/ADM, KYO-1, HEL and CMK, which had relative resistance index values of 2 or more to vincristine (VCR), vindesine, vinblastine, ADM, daunorubicin, mitoxantrone (MIT), etoposide (VP-16) and actinomycin-D (ACT-D). The level of resistance to VCR and ADM in these cell lines decreased significantly in the presence of 10 microM verapamil in vitro. Significant expression of mRNA of P-gp gene was also detected in K562/ADM, KYO-1 and HEL. MRK16-F(ab')2 did not react with 36 other cell lines. Among them, three cell lines, PL-21, P31/FUJ and KOPM-28, had relative resistance index values of 2 or more to anthracyclines, MIT and VP-16, but not to vinca alkaloids or ACT-D. The level of ADM-resistance in these cell lines did not decrease significantly in the presence of 10 microM verapamil. Five cell lines, ATL-1K, HL-60, KMOE-2, ML-1 and U266, had relative resistance index values of 2 or more to some of the drugs, but not to the others, and 19 other cell lines did not. These results indicate that the reactivity of MRK16-F(ab')2 correlates with a relative resistance index of 2 or more to all these drugs in cultured human leukemia and lymphoma cell lines. PMID- 2575607 TI - Association of dopaminergic fibers with corticotropin releasing hormone (CRH) synthesizing neurons in the paraventricular nucleus of the rat hypothalamus. AB - Catecholamines are known to exert a central influence on the hypothalamo hypophyseal-adrenal neuroendocrine system. The selective dopaminergic innervation of the hypothalamic paraventricular nucleus (PVN) and putative relationships between dopaminergic fibers and corticotropin releasing hormone (CRH) synthesizing neurons were studied in the male rat by means of immunocytochemistry following the elimination of noradrenergic and adrenergic inputs to the hypothalamus. A 3.0-mm-wide coronal cut was placed unilaterally in the brain at the rostral level of the mesencephalon. All neuronal structures from the cortex to the ventral surface of the brainstem, including the ascending catecholaminergic fiber bundles were transected. This surgical intervention resulted in the accumulation of dopamine-beta-hydroxylase (DBH)-immunoreactivity in axons proximal to the cut, and an almost complete disappearance of DBH activity in those located distal to the lesion. Two weeks following the operation, DBH immunoreactivity was significantly diminished in the PVN located on the side of lesion, while tyrosine hydroxylase (TH)-immunoreactivity was present in a substantial number of fibers in the same nucleus. Both DBH- and TH immunoreactive axons were preserved in the contralateral PVN. Simultaneous immunocytochemical localization of either DBH- or TH-IR fibers and corticotropin releasing hormone-synthesizing neurons in the hypothalami from brainstem lesioned, colchicine treated animals revealed that the distribution of catecholaminergic fibers and CRH neurons is homologous within the PVN of the intact side. Only a few scattered DBH-immunoreactive axons were detected among CRH-producing neurons in the PVN on the side of the lesion. In contrast, many tyrosine hydroxylase containing neurons and neuronal processes were observed on the lesioned side and the TH-IR fibers established juxtapositions with CRH synthesizing neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575609 TI - Co-amplification of c-myc and c-erbB-2 oncogenes in a poorly differentiated human gastric cancer. AB - c-erbB-2 oncogene has been reported to be frequently amplified in differentiated, tubular type of gastric cancer. Here we report a human gastric cancer which bore co-amplified c-myc and c-erbB-2 oncogenes: a portion of the amplified c-erbB-2 oncogene was found to be rearranged. Furthermore, c-myc and c-erbB-2 oncogenes were over-expressed in the tumor cells. In contrast to the previous reports, this gastric adenocarcinoma was classified as a poorly differentiated type, and was highly tumorigenic in nude mice. These results might suggest that activated c-myc and c-erbB-2 oncogenes co-operate and influence the malignant state of some gastric carcinomas. PMID- 2575611 TI - Immunological and genetical relatedness of type-1 and type-2 fimbriae in salmonellas of serotypes Gallinarum, Pullorum and Typhimurium. AB - The fimbriae of 50 strains of serotype Gallinarum and 35 strains of serotype Pullorum of the genus Salmonella were compared with the type-1 fimbriae of serotype Typhimurium strains by immune electron microscopy and dot blot hybridization tests with gene probes for type-1 fimbriation in Typhimurium. The fimbriae of Gallinarum and Pullorum strains were coated with Typhimurium type-1 fimbrial antiserum and probes hybridized strongly with DNA of Gallinarum and Pullorum strains under stringent conditions. Furthermore, when Typhimurium type-1 fimbrial antiserum, that had been absorbed with fimbriate Gallinarum or Pullorum bacteria, was used in immune gold labelling experiments, it was shown that residual antibody recognized sites of possible adhesin incorporation at intervals along the length of Typhimurium type-1 fimbriae. These findings suggest that the type-2 fimbriae produced by all Gallinarum and Pullorum strains are non-adhesive forms of adhesive, type-1 fimbriae. This observation is of interest because type 1 fimbriae have never been reported in naturally occurring strains of these two avian-adapted serotypes. PMID- 2575610 TI - Expression of P-glycoprotein mRNA in human gastric tumors. AB - We have isolated a cDNA clone, pCA12-2, from a lambda gt11 cDNA library of an adriamycin-resistant subline of human myelogenous leukemia K562 (K562/ADM) by plaque hybridization with the 2.6 kb genomic probe of P-glycoprotein reported previously. The cDNA pCA12-2 was identified as the 3'-part of P-glycoprotein cDNA by dideoxy sequencing. By using the cDNA probe, expression of P-glycoprotein mRNA was examined in human gastric xenograft lines transplanted in nude mice and clinical samples of human gastric normal tissues and tumors. Five gastric tumor xenograft lines expressed low but significant levels of P-glycoprotein mRNA. The extent of expression was higher in some cases than that observed for R1-3, a weakly drug-resistant subline of K562. Normal gastric tissues from three patients expressed similar levels of P-glycoprotein mRNA and the extent of expression was slightly higher than that of R1-3. Two of three gastric tumor samples expressed higher levels of mRNA than normal gastric tissues. These results suggest that the intrinsic insensitivity of human gastric cancers to chemotherapy could be partly explained by the expression of P-glycoprotein. PMID- 2575612 TI - Aminopeptidase M from human liver. I. Solubilization, purification, and some properties of the enzyme. AB - Aminopeptidase M [EC 3.4.11.2] was purified 772-fold to homogeneity from the microsomal fraction of human liver, with a yield of 18.9%, by a combination of solubilization with 0.5% Triton X-100 and then 1 M urea and chromatography on columns of DEAE-cellulose, hydroxylapatite, Butyl-Toyopearl, and Sephacryl S-300. The purified enzyme had a molecular weight of 140,000 by SDS-polyacrylamide gel electrophoresis and of 280,000 by gel filtration on a column of TSK gel 2000 SW. It was reconstituted into proteoliposomes with asolectin, showing its amphiphilic nature. The aminopeptidase M from liver was found to be efficiently inhibited by bile acids. The enzyme was almost completely inhibited by chenodeoxycholic acid and 70-90% inhibited by cholic acid at a concentration of 6 mM. The extent of inhibition by conjugated and unconjugated bile acids was in the order: unconjugated greater than glycoconjugated greater than tauroconjugated bile acid, independent of the nature of the substrates used. The inhibition by the various bile acids was totally reversible. Further, it was immunochemically revealed that a considerable amount of liver aminopeptidase M was released into the bile duct. The role of the aminopeptidase M on the bile canalicular membrane and of the enzyme released in the bile duct is discussed in relation to the effects of bile acids. PMID- 2575613 TI - Aminopeptidase M from human liver. II. Kinetic analysis of inhibition of the enzyme by bile acids. AB - The mechanism of inhibition of aminopeptidase M by bile acids was analyzed by application of the specific velocity plot that was introduced by Baici [Eur. J. Biochem. 119, 9-14 (1981)]. Kinetic studies with three bile acids (cholic acid, deoxycholic acid, and chenodeoxycholic acid) and three substrates (Leu-Met, Leu Gly, and Leu-pNA) showed that the inhibition constants Ki for the bile acids were appreciably different from each other, but that the Ki for each was not affected by the substrates used, being 0.89-1.03 mM for cholic acid, 0.42-0.66 mM for deoxycholic acid, and 0.24-0.31 mM for chenodeoxycholic acid. The values of the kinetic coefficient alpha [(apparent Ks in the presence of inhibitor)/Ks] for cholic acid with Leu-Met and Leu-Gly were 9.0 and 2.5, respectively. These values were very similar to those for chenodeoxycholic acid (7.0 and 2.7) but smaller than those for deoxycholic acid (21 and 11). The values of the other kinetic coefficient beta [(apparent kp in the presence of inhibitor)/kp] were 0 except in the case of the combinations of Leu-Gly with cholic acid (0.33) and Leu-Gly with chenodeoxycholic acid (0.13). On the basis of these kinetic parameters, the inhibitions by bile acids were classified into 4 types: competitive noncompetitive linear mixed type (1 less than alpha less than infinity, beta = 0), noncompetitive-uncompetitive linear mixed type (0 less than alpha less than 1, beta = 0), pure noncompetitive type (alpha = 1, beta = 0), and hyperbolic mixed type (1 less than alpha less than infinity, 0 less than beta less than 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575614 TI - Comment on 'The Influence of Running Velocity and Midsole Hardness on External Impact Forces in Heel-Toe-Running'. AB - Researchers not sufficiently sensitive to statistical power may interpret non significant results as demonstrating that the conditions made no difference. Related issues include performer variability, sample size and effect size as they relate to experimental design. Examination of these factors suggests that caution must be exercised when interpreting the results of experimental data. PMID- 2575615 TI - ATP, alpha,beta-methylene ATP and suramin as tools for characterization of vascular P2x receptors in the pithed rat. AB - 1. In pithed rats, the blood pressure effects of ATP, alpha,beta-methylene ATP (mATP), alpha-adrenoreceptor agonists and of electrical stimulation of the thoracolumbar sympathetic outflow were studied in the absence and presence of mATP, suramin and adrenoreceptor antagonists. 2. ATP elicited an initial rise in mean blood pressure followed by a decrease and a second increase. mATP produced a short-lived increase in blood pressure, whereas equieffective doses of noradrenaline, methoxamine and B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H thiazolo-(5,4-d)-azepine) produced a more prolonged, biphasic pressor response. 3. In the presence of high doses of prazosin, rauwolscine plus propranolol, the initial vasopressor and the vasodepressor effect to ATP were not affected, whereas the delayed vasopressor response to ATP, the vasopressor response to electrical stimulation and even more so that to noradrenaline were suppressed. 4. Suramin, which by itself produced a short-lived decrease, followed by a persistent increase in blood pressure, decreased the pressor responses to ATP (initial phase), to mATP and to electrical stimulation without affecting the fall and second rise in blood pressure elicited by ATP and the pressor response to noradrenaline. 5. Desensitization of P2x receptors by a low dose of mATP abolished the initial vasopressor response to ATP but failed to affect the subsequent blood pressure effects of ATP as well as the pressor responses to noradrenaline and electrical stimulation. A high dose of mATP, in addition, decreased the vasopressor responses to noradrenaline, methoxamine, B-HT 920 and electrical stimulation; the delayed effects of ATP on blood pressure were not changed. 6. The electrically induced increase in blood pressure subsequent to administration of high doses of prazosin, rauwolscine plus propranolol was diminished by suramin and by the low and high dose of mATP. 7. The present study suggests that under certain circumstances ATP, which, added exogenously, has a triphasic effect on mean blood pressure, contributes to the electrically induced vasopressor response by activation of P2x receptors. PMID- 2575616 TI - Towards an in vitro system for studying clathrin-coated pit function. AB - To elucidate the molecular basis of coated pit function, we are developing a method for reconstituting the endocytic cycle in a cell-free system. Using purified membranes attached to a solid substratum, we have successfully reconstituted coated pit assembly. We now show that the endogenous coated pits on these membranes spontaneously round up and leave the membrane at 37 degrees C. As measured by radioimmunoassay, clathrin loss is both pH- and temperature dependent. The loss is also inhibited by pretreating the membranes with apyrase at 37 degrees C, which suggests that nucleotide triphosphates are required. PMID- 2575617 TI - Cross-linking of microtubules by microtubule-associated proteins (MAPs) from the brine shrimp, Artemia. AB - Microtubules induced with taxol to assemble in cell-free extracts of the brine shrimp, Artemia, are cross-linked by microtubule-associated proteins (MAPs). When the MAPs, extracted from taxol-stabilized microtubules with 1 M-NaCl are co assembled with purified Artemia or mammalian neural tubulin, reconstitution of cross-linking between microtubules occurs. The most prominent non-tubulin protein associated with reconstituted cross-linked microtubules has a molecular weight of 49,000 but we cannot yet exclude the possibility that other proteins may be responsible for the cross-linking. Cross-linkers are separated by varying distances while cross-linked microtubules, prepared under different conditions, are 6.9-7.7 nm apart. Cross-linking of microtubules by MAPs occurs whether MAPs are added to assembling tubulin or to microtubules, and it is not disrupted by ATP. The MAPs are heat-sensitive and do not stabilize microtubules to cold. Immunological characterization of Artemia MAPs on Western blots indicates that Artemia lack MAP 1, MAP 2 and tau. Our results clearly demonstrate that Artemia contain novel MAPs with the ability to cross-link microtubules from phylogenetically disparate organisms in an ATP-independent manner. PMID- 2575618 TI - Monoclonal antibody against the centrosome. AB - A monoclonal antibody, MPM-13, raised against mitotic HeLa cell extracts recognized a perinuclear area in interphase cells and spindle poles in mitotic cells of human, mouse, Chinese hamster and sea urchin. On immunoblots MPM-13 recognized a major protein band at 43 X 10(3) Mr and a variable minor band at 56 X 10(3) Mr in both mitotic and interphase HeLa cells. These antigens were detectable in a variety of mammalian cells as well as in the unicellular ciliate Tetrahymena. In cells arrested in mitosis by colcemid and stained with MPM-13 by indirect immunofluorescence, numerous fluorescent speckles were seen throughout the cytoplasm. Reversal of colcemid block in Chinese hamster ovary (CHO) cells by washing resulted in the reappearance of a fluorescent patch at the poles of the re-formed spindles. In HeLa cells arrested in mitosis by the microtubule stabilizing drug taxol, MPM-13 stained a large fluorescent patch encircled by dark metaphase chromosomes. This pattern indicated the failure of centrioles to move to the opposite poles in the presence of taxol. These data indicate that the MPM-13 antigens are associated with the colcemid-sensitive pericentriolar material from which microtubules originate but not with the centrioles themselves. It is also clear that these antigens are highly conserved during evolution. PMID- 2575619 TI - Undertreating pain--caution or cruelty? PMID- 2575620 TI - Automated high-performance liquid chromatographic assay for the beta-carboline derivative Abecarnil in plasma. PMID- 2575621 TI - Simultaneous determination of (R)- and (S)-celiprolol in human plasma and urine: high-performance liquid chromatographic assay on a chiral stationary phase with fluorimetric detection. AB - The quantitative enantiospecific determination of the beta 1-selective adrenergic antagonist (R,S)-celiprolol in human plasma and urine is described. It involves a two-step liquid-liquid extraction of celiprolol from biological material and separation of the underivatized enantiomers by high-performance liquid chromatography on a chiral stationary phase (cellulose tris-3,5-dimethylphenyl carbamate, coated on silica gel) with fluorimetric detection. R-(+)-Propranolol was used as an internal standard. The detection limits of 1.5 ng/ml enantiomer in plasma and 2.5 ng/ml enantiomer in urine at signal-to-noise ratios higher than 3 permit the performance of pharmacokinetic studies after therapeutic doses. PMID- 2575622 TI - Is pregnancy the best treatment for hyperprolactinaemia? AB - This paper reports the changes in prolactin levels after 12 spontaneous and 52 induced pregnancies in 54 women with unambiguous hyperprolactinaemia (median plasma prolactin levels 67.5 ng/ml, range 40-400). Twenty-three of the patients showed radiological evidence of prolactinoma. The pregnancies were induced in 37 patients by bromocriptine, in nine by metergoline, in two by lisuride and in four by other treatments. Of the 64 pregnancies, 16 ended in spontaneous abortion, while 48 went to term. Follow-up was continued for at least 6 months after delivery or until the end of lactation. In a control group of 32 hyperprolactinaemic women (median prolactin 70 ng/ml, range 40-400) not wishing to become pregnant, prolactin changes were similarly registered over a mean period of 15 months without any treatment (range 6-38 months). After pregnancy, a significant downward trend of plasma prolactin was observed in the puerperal women with a 'normalization' rate of 17%. No changes were observed in the 32 controls who did not become pregnant. PMID- 2575623 TI - Localized myxedema on the nasal dorsum in a patient with Graves' disease: report of a case. AB - We report the case of a 56-year-old Japanese female with Graves' disease associated with localized myxedema on the nasal dorsum. The patient developed localized myxedema concomitantly with hyperthyroidism before antithyroid therapy was given. The lesion was totally removed surgically, as it was small and well circumscribed. Although unusual locations of localized myxedema have been reported elsewhere, there is to date no case of localized myxedema on the nasal dorsum without involvement of the pretibial area reported in the literature. We discuss this unique feature of our patient. PMID- 2575624 TI - Pre- and peroperative diagnosis of metastatic pheochromocytoma in multiple endocrine neoplasia type 2a. AB - A 37-year-old woman with a multiple endocrine neoplasia type 2a underwent bilateral adrenalectomy and total thyroidectomy with parathyroidectomy in 1977. The left-sided pheochromocytoma was considered to be malignant. Seven yr after the initial operation, an enhanced urinary excretion-ratio of N methyladrenaline/adrenalin suggested the possible presence of either persistent or metastatic pheochromocytoma Iodine-123-labeled metaiodobenzylguanidine scintigraphy (I-123 MIBG) showed a hot spot in the right lung. However, repeated chest-X-rays and computed tomographic scanning of the thorax remained negative. Anatomical localization of the lesion was finally obtained with magnetic resonance imaging. The surgical removal of the small pheochromocytoma was guided by the gamma-ray emission of I-123 MIBG administered iv before the operation. This case report illustrates the usefulness of new analytical methods and of new imaging techniques in the diagnosis and management of metastatic pheochromocytoma. PMID- 2575626 TI - Enterobacter cloacae in a haematology/oncology ward--first impressions. AB - The observation that Enterobacter cloacae has emerged as a cause of infection in a haematology/oncology ward prompted a prospective study over an eight-month period. Sensitivity to antibiotics, plasmid screening and typing methods were used to describe the epidemiology of the organism which was isolated from 22 patients. There was evidence of a limited amount of cross infection. No common sources were found. A large number of distinct strains were identified. E. cloacae infection was associated with prolonged profound leucopenia and broad spectrum antibiotic therapy. PMID- 2575627 TI - Two sources of contamination of a hydrotherapy pool by environmental organisms. AB - As a result of occasional water discolouration, the hydrotherapy pool of a large teaching hospital was monitored for free and combined chlorine, alkalinity, calcium hardness, total dissolved solids and cyanuric acid levels together with bacteriological analysis. The hose pipe supplying the pool and the dual water pumps were also examined as potential sources of bacterial contamination. The pool water yielded high counts of Pseudomonas vesicularis, Pseudomonas aeruginosa, and CDC Group IV C2, even in the presence of adequate levels of free chlorine. This was found to be due to high concentrations of cyanuric acid which resulted in a 'chlorine lock'. The source of the P. vesicularis and CDC Group IV C2 was found to be the pool hose and this problem was alleviated by flushing it with water each day before use. The source of the P. aeruginosa was the pool pumps, and was eradicated by regularly shock dosing them with 6-8 ppm of free chlorine. PMID- 2575629 TI - A laboratory-confirmed outbreak of rifampicin-methicillin resistant Staphylococcus aureus (RMRSA) in a newborn nursery. AB - The routine laboratory monitoring of methicillin-resistant strains of Staphylococcus aureus (MRSA) at a large teaching hospital led to the detection of a new, multiply-resistant strain of MRSA, which was resistant not only to penicillin, oxacillin, methicillin, cephamandole, erythromycin, tetracycline, kanamycin and gentamicin but also to rifampicin and sulphamethoxazole trimethoprim. The rifampicin-methicillin resistant strain of S. aureus (RMRSA) was first detected in blood cultures of babies from the newborn nursery. A bacteriological investigation of the nursery revealed the source to be a paediatric medical officer who was colonised with the resistant strain, and who at the time was receiving rifampicin for pulmonary tuberculosis. The rifampicin resistance was presumably acquired during rifampicin therapy. The outbreak in the nursery was brought to an abrupt end by treatment of the colonised medical officer with mupirocin, applied nasally twice a day for a week, and by the introduction of standard infection-control measures. Reference laboratory assistance was needed to confirm the initial assumption that the outbreak was caused by a single strain. PMID- 2575628 TI - The prevention of infection with Staphylococcus aureus in continuous ambulatory peritoneal dialysis. AB - We describe the control of wound infection with Staphylococcus aureus in patients undergoing continuous ambulatory peritoneal dialysis at St. Thomas' Hospital. Forty-nine percent of 61 catheters inserted in 1985 and 1986 became infected, and the majority of these infections were acquired in hospital. Infection was impossible to eradicate and was frequently associated with the subsequent development of S. aureus peritonitis, which was the most important cause of catheter loss. Strict adherence to aseptic techniques for catheter insertion and care, combined with eradication of S. aureus carriage, reduced the infection rate to 12% for the 50 catheters inserted in 1987, abolished hospital-acquired infection and reduced the S. aureus peritonitis rate tenfold, without the use of prophylactic antibiotics. S. aureus infection is a serious but avoidable complication of continuous ambulatory peritoneal dialysis. PMID- 2575630 TI - The acquisition of antibiotic resistant coagulase-negative staphylococci by aortic graft recipients. AB - The staphylococcal flora of the groin and perianal area was studied in 12 patients undergoing aortic grafts and 3 patients having repair of ventral abdominal hernias. A total of 892 isolates of coagulase-negative staphylococci (CNS) were identified and their antibiotic resistance determined. The species most frequently isolated were S. epidermidis and S. haemolyticus with the latter showing the highest incidence of antibiotic resistance. Five of 15 patients had CNS resistant to methicillin and gentamicin on admission. The effect of pre operative bathing with chlorhexidine was studied in 6 patients and appeared to reduce the acquisition of multi-resistant CNS in the week after operation. PMID- 2575625 TI - Diagnostic problems in pheochromocytoma. PMID- 2575631 TI - Are ECG Welsh cup electrodes effectively cleaned? AB - Re-usable Welsh electrocardiograph (ECG)-electrodes are potential vehicles for cross infection. This study confirmed that in-use ECG-electrodes are frequently contaminated with organisms such as coagulase-negative staphylococci and Gram negative bacilli. The efficacy of five cleaning procedures was evaluated. Immersing the electrodes in water at 60 degrees C for one hour was the most effective method of decontamination tested, following challenge with a standardised suspension of Staphylococcus saprophyticus. Significant contamination persisted following simple cleaning measures. It is suggested that this was promoted by the inadequate removal of electrode gel which provided a protective environment for microorganisms. PMID- 2575633 TI - The effect of air on the moist-heat resistance of Bacillus stearothermophilus spores. AB - The presence of air in an autoclave chamber and load is generally considered to reduce the lethal effect of the process on bacterial spores. In this study, the heat inactivation of spores of Bacillus stearothermophilus (NCIB 8224) was measured in the presence and absence of air at 100% relative humidity. The results confirm that air significantly enhances the lethality of moist-heat on this strain of B. stearothermophilus. PMID- 2575632 TI - Air bacterial and particle counts in total hip replacement operations using non woven and cotton gowns and drapes. AB - Air bacterial and particle counts were obtained in a conventionally ventilated operating theatre, during 8 operations for total hip replacement performed using synthetic non-woven fabrics as drapes for the patients and gowns for the staff (trousers and stockings were of conventional cotton material), ('non-woven' group), and in 8 corresponding operations using conventional cotton fabrics ('cotton' group). No significant difference between the groups with regard to air bacterial counts was observed. The use of cotton fabrics was associated with substantially higher particle counts, probably due to particles from the cotton textiles themselves. No significant correlation was observed between the bacterial and particle counts, indicating that these came from different sources and that the particles were mainly of sterile origin. Thus, the benefit of the synthetic, non-woven fabrics in hip replacement surgery, when these fabrics are used to cover theatre staff only partially in the form of gowns, seems questionable with regard to the reduction of air bacterial counts. On the other hand, the surgical textiles of non-woven material improve the purity of the operating theatre since unlike cotton fabrics they do not produce and disperse particles in the air. PMID- 2575634 TI - Nosocomial gastroenteritis in paediatric patients. AB - Between November 1982 and April 1985, 2228 children under the age of 5 years with acute gastroenteritis were admitted to the paediatric isolation ward of Queen Mary Hospital, Department of Paediatrics, University of Hong Kong. In 56.2% the causative agent was identified as rotavirus, Salmonella, Campylobacter, Shigella, Escherichia coli or a combination of these pathogens. Our isolation procedures included cohort nursing of all diarrhoeal patients in two separate rooms (each accommodating 6 patients), barrier gowns and stringent handwashing with chlorhexidine. A total of 163 cases (13.4% of all positive cases) were identified as nosocomial infections. Rotavirus was the responsible agent for nosocomial infection in 128 cases (20% of all rotavirus infection). There were 35 patients with bacterial nosocomial infection, (7% of all the bacterial positive cases). Nosocomial rotavirus gastroenteritis was 3.4 times more frequent than nosocomial gastroenteritis due to bacterial pathogens. We conclude that modification of our present isolation procedures is necessary in order to reduce rotavirus nosocomial infection. PMID- 2575635 TI - Methicillin-resistant Staphylococcus aureus: a ten-year survey in a Dublin hospital. AB - We undertook a retrospective, longitudinal survey to monitor the changing incidence, phage types and patterns of antibiotic resistance of methicillin resistant Staphylococcus aureus (MRSA) in St Laurence's Hospital (SLH), Dublin over the last 10 years. Following a peak in 1979, the incidence of MRSA has gradually decreased to around 17% of S. aureus isolates in 1986, almost identical to its incidence 10 years before. However, the spectrum of antibiotic resistance among these organisms remains broad and this seems to be at least partially related to antibiotic usage. Many strains could not be phage typed and others were typable only by the additional phage 90. This has severely limited the usefulness of phage typing in the tracing of sources of outbreaks. Thus, there is a need for a more specific method of typing as well as a rational antibiotic policy, to successfully monitor and curtail the hospital spread of MRSA. PMID- 2575636 TI - An outbreak of acinetobacter septicaemia in a neonatal intensive care unit. AB - We describe an outbreak of Gram-negative septicaemia due to a rare, non fermenting, aerobic organism, Acinetobacter calcoaceticus var. lwoffi. The outbreak occurred on a neonatal unit and was confined to babies who were receiving parenteral nutrition. Seven babies developed septicaemia within 24 hours. The source of the outbreak was never firmly established, but contamination of the parenteral nutrition fluid was considered most likely. All 7 babies recovered uneventfully after a week's course of intravenous ceftazidime. Thrombocytopenia was an unexpected feature of this infection. PMID- 2575637 TI - Hospital Infection Research Laboratory, Birmingham--25th anniversary. PMID- 2575638 TI - Pseudomonas paucimobilis in purified water for hospital use. PMID- 2575640 TI - Environmental hazards from a hospital incinerator. PMID- 2575639 TI - Survey of viruses of the gut in 10,477 children admitted to general paediatric wards from 1981 to 1986. PMID- 2575641 TI - Surveillance skin cultures in central venous catheter sepsis. PMID- 2575642 TI - Methicillin-resistant Staphylococcus aureus in a general hospital in Brazil. PMID- 2575643 TI - Gross genetic differences among substrains of NZB mice. AB - Substrains of NZB mice have been compared by Southern blot analysis using several probes. The restriction fragment length polymorphism of probes derived from the Igh-V, Igk-V, Tcr alpha-C loci and of the long terminal repeat of the mouse mammary tumour virus revealed that NZB/BlLwPtIbm were grossly different from NZB/BlNJ and NZB/BlOla. Comparison with mouse strains of the Igk-V haplotypes a and d suggested that NZB/BlLwPtIbm contain genetic material of the C58 mouse strain. PMID- 2575644 TI - [Gastric microflora in patients receiving H2-blocker]. AB - The gastric microflora of 21 cases receiving histamine H2-receptor antagonists (H2-blocker) were studied. Patients not given H2-blocker were also examined for gastric microflora. The gastric pH of patients who were receiving H2-blocker ranged from 1.91 to 6.51 (mean, 4.32). The gastric pH of over 5.00 was seen in 10 cases. Aerobic bacteria were isolated from 20 cases (95%). Aerobic bacterial counts per ml of gastric aspirates correlated positively with the pH of those aspirates but was little correlation between the pH of the gastric aspirates and the number of anaerobic bacteria of the samples, which were positive in 7 cases (33%). Candida and Staphylococcus were predominant isolates with positive rates of 82% and 41%, respectively. While Fusobacterium was isolated from 33% of the samples, none of the Bacteroides fragilis group organisms were isolated. It was also observed in the control group that aerobic and anaerobic bacteria were isolated from the gastric aspirates with high pH. These results suggest that in patients receiving H2-blocker anaerobes as well as aerobes may have the possibility to become pathogen for aspirate pneumonia and so on because of the overgrowth of anaerobic bacteria in the gastric fluid. PMID- 2575647 TI - Evolutionary and contemporary biology of elasmobranchs. PMID- 2575646 TI - Gamma-glutamyltransferase: evaluation of a new method. AB - The determination of gamma-glutamyltransferase using a new donor substrate, L gamma-glutamyl-3,5-dibromo-4-hydroxyanilide, was evaluated in two laboratories. Between-run and within-run precision are excellent and comparable with those of other methods for the determination of gamma-glutamyltransferase. The activity concentrations of gamma-glutamyltransferase from human sera obtained with the new donor substrate were slightly higher than those obtained with L-gamma-glutamyl-4 nitroanilide. The reverse was found for sera enriched with gamma glutamyltransferase of animal origin. Temperature conversion factors (activity 37 degrees C/activity 30 degrees C) are given. The advantages of this method are discussed. The new assay appears to provide a good alternative for the method with L-gamma-glutamyl-4-nitroanilide or one of its derivatives as substrate. PMID- 2575645 TI - Cryptorchidism: a registry based study in Sweden on some factors of possible aetiological importance. AB - STUDY OBJECTIVE: To examine the epidemiological characteristics of boys with cryptorchidism. DESIGN: Cohort survey using the Swedish personal identification code and Medical Birth Registry to link cryptorchid boys with their pregnancy and delivery data. They were compared with the total population of male births during the same period. SUBJECTS: 2861 cryptorchid boys born in Sweden between 1973 and 1982 were identified. Of these 437 could not be linked with their Medical Birth Registry information for various reasons, or were excluded because they were under 1 year of age at the end of 1982, leaving 2424 cases for study. The reference population comprised all boys born in Sweden during the same period (n = 458,601). MEASUREMENTS AND MAIN RESULTS: For each study variable, the observed number of cases among boys with cryptorchidism was compared with the expected number calculated from the whole population. A significant increase in intensity ratio for cryptorchidism was found with the first birth, caesarean section, toxaemia of pregnancy, and certain congenital abnormalities (hypospadias and subluxation of the hip). It was also more common in small for dates infants. There was a seasonal variation in cryptorchidism, with increased incidence in January-March. CONCLUSIONS: Cryptorchidism may be caused by hormonal influences during pregnancy, which could be affected by utero-placental factors involving placental dysfunction or by daylight hours, through pineal activity. PMID- 2575648 TI - Chromosome markers and karyology of selachians. AB - Among vertebrates, chondrichthyans exhibit peculiar karyotypes and total amount and composition of DNA very different from those of tetrapods and teleosteans. Selachians have relatively large genome sizes (more than 30 pg/N), which are inversely related to the fraction rich in adenine-thymine. Moreover, they show a high chromosome number (2n = 60-100), decreasing in the most specialized species. The karyotypes of Scyliorhinus stellaris, Torpedo ocellata, and T. marmorata have been investigated by several techniques in order to distinguish particular genome fractions along the chromosome arms. C-banding appears to be positive in most telomeric regions in Scyliorhinus and at the interstitial level in the two torpedo species. Studies with restriction enzymes (RE) have just been started in selachians, employing ALU I and HIND III in Scyliorhinus stellaris. The former digests the whole chromosome except the telomeric regions, revealing patterns similar to the C-bands. The latter cuts the chromosomes into several interstitial regions, producing G-bands. Other RE are being studied, which will allow identification in situ of qualitative differences in the various DNAs. PMID- 2575649 TI - Flagellar cells and ciliary cells in the renal tubule of elasmobranchs. AB - Flagella or cilia are present on most epithelial cells in the renal tubule of elasmobranch fishes (little skate, spiny dogfish, smooth dogfish, Atlantic sharpnose, scalloped hammerhead, cow-nosed ray). Flagellar cells, those with numerous flagella ordered in one, two, or more rows on the luminal surface, are shown here for the first time in a vertebrate. The flagellar cells are intercalated among other epithelial cells, each bearing a single cilium, from Bowman's capsule to the third subdivision of the intermediate segment of the nephron. The flagella form undulated ribbons up to 55 microns long. In every ribbon the axis of the central pair of microtubules in the axoneme is oriented parallel to the long axis of the flagellar row. This suggests a beat perpendicular to these two axes. The arrangement of the flagella in ribbons most likely promotes movement of glomerular filtrate down the renal tubule. Cells bearing numerous cilia occur in the large collecting ducts of spiny dogfish but without apparent preferential orientation of the cilia. PMID- 2575650 TI - Regulation of spermatogenesis: the shark testis model. AB - Spermatogenesis is a unique developmental sequence dependent on FSH and androgen. Due to the complex organization of the mammalian testis, however, mechanistic details of regulation are largely unknown. Using the dogfish shark (Squalus acanthias) in which there is a cystic mode of spermatogenesis and a topographic separation of different germ cell stages within the testis, we have obtained new information of general relevance on stage-related biochemical and morphological changes and have proposed a model in which steroids serve as parahormonal regulators of the spermatogenic progression. In addition, techniques developed for culturing staged spermatocysts (intact Sertoli/germ cell units) and isolated, staged Sertoli cells demonstrate the usefulness of this model for studying spermatogenic regulation under defined conditions in vitro. PMID- 2575651 TI - Brain variation and phylogenetic trends in elasmobranch fishes. AB - A cladistic analysis utilizing the out-group criterion to establish the phylogenetic polarity of neural features among living chondrichthyans leads to the conclusion that the earliest chondrichthyans possessed relatively small brains. Relative brain size appears to have increased independently in some myliobatiforms and in the common ancestor of heterodontid and galeomorph sharks. Furthermore, the brains of the earliest chondrichthyans must have exhibited a wide rhomboid fossa of the medulla, an unfoliated cerebellar corpus divided into anterior and posterior lobes, a bilobed and laminated optic tectum with the majority of the cell bodies located periventricularly, a moderately developed midbrain octavolateralis complex, and a telencephalon consisting of sessile olfactory bulbs and paired cerebral hemispheres with extensive lateral ventricles and thin walls. The corpus of the cerebellum has increased dramatically in size and has become complexly foliated independently in some batoids and galeomorph sharks. Similarly, the majority of tectal neurons have migrated away from a periventricular zone in all living elasmobranchs resulting in two distinctly derived patterns, compared to that in holocephalimorphs, but the polarity of these patterns among elasmobranchs is uncertain. The midbrain octavolateralis complex is uniquely derived in all living batoids, but two patterns appear to occur in other chondrichthyans, and, again, their polarity is uncertain. Different portions of the telencephalic roof appear to have hypertrophied in holocephalimorphs, in some batoids, and in some galeomorphs. An examination of pertinent details of chondrichthyan general biology reveals that the biological significance of most chondrichthyan neural trends is unknown. PMID- 2575652 TI - Regulation of cGMP levels by guanylate cyclase in truncated frog rod outer segments. AB - Cyclic GMP is the second messenger in phototransduction and regulates the photoreceptor current. In the present work, we tried to understand the regulation mechanism of cytoplasmic cGMP levels in frog photoreceptors by measuring the photoreceptor current using a truncated rod outer segment (tROS) preparation. Since exogenously applied substance diffuses into tROS from the truncated end, we could examine the biochemical reactions relating to the cGMP metabolism by manipulating the cytoplasmic chemical condition. In tROS, exogenously applied GTP produced a dark current whose amplitude was half-maximal at approximately 0.4 mM GTP. The conductance for this current was suppressed by light in a fashion similar to when it is activated by cGMP. In addition, no current was produced in the absence of Mg2+, which is known to be necessary for the guanylate cyclase activity. These results indicate that guanylate cyclase was present in tROS and synthesized cGMP from exogenously applied GTP. The enzyme activity was distributed throughout the rod outer segment. The amount of synthesized cGMP increased as the cytoplasmic Ca2+ concentration of tROS decreased, which indicated the activation of guanylate cyclase at low Ca2+ concentrations. Half maximal effect of Ca2+ was observed at approximately 100 nM. tROS contained the proteins involved in the phototransduction mechanism and therefore, we could examine the regulation of the light response waveform by Ca2+. At low Ca2+ concentrations, the time course of the light response was speeded up probably because cGMP recovery was facilitated by activation of the cyclase. Then, if the cytoplasmic Ca2+ concentration of a photoreceptor decreases during light stimulation, the Ca2+ decrease may explain the acceleration of the light response during light adaptation. In tROS, however, we did observe an acceleration during repetitive light flashes when the cytoplasmic Ca2+ concentration increased during the stimulation. This result suggests the presence of an additional light dependent mechanism that is responsible for the acceleration of the light response during light adaptation. PMID- 2575654 TI - Escherichia coli tolQ mutants are resistant to filamentous bacteriophages that adsorb to the tips, not the shafts, of conjugative pili. AB - The tolQ (previously fii) mutation in Escherichia coli K12 inhibits infection by filamentous bacteriophages f1 and IKe but not by RNA-containing phage f2. This work extends these observations to other plasmid-specific bacteriophages including various filamentous. RNA-containing, and lipid-containing isolates. Only tip-adsorbing filamentous phages were affected by tolQ and not shaft adsorbing ones. Electron microscopy showed that RP4-specific filamentous phage Pf3 was one of the latter kind. Several tip-adsorbing filamentous phages inhibited conjugation between tolQ strains carrying their specific plasmids, implicating the phage receptors (conjugative pili) as mating organelles. tolQ mutant strains were as proficient as their parents in conjugation mediated by a wide range of plasmids. PMID- 2575653 TI - Ammonium assimilation by Candida albicans and other yeasts: evidence for activity of glutamate synthase. AB - Activities and properties of the ammonium assimilation enzymes NADP+-dependent glutamate dehydrogenase (GDH), glutamate synthase (GOGAT) and glutamine synthetase (GS) were determined in batch and continuous cultures of Candida albicans. NADP+-dependent GDH activity showed allosteric kinetics, with an S0.5 for 2-oxoglutarate of 7.5 mM and an apparent Km for ammonium of 5.0 mM. GOGAT activity was affected by the buffer used for extraction and assay, but in phosphate buffer, kinetics were hyperbolic, yielding Km values for glutamine of 750 microM and for 2-oxoglutarate of 65 microM. The enzymes GOGAT and NADP+ dependent GDH were also assayed in batch cultures of Saccharomyces cerevisiae and three other pathogenic Candida spp.: Candida tropicalis, Candida pseudotropicalis and Candida parapsilosis. Evidence is presented that GS/GOGAT is a major pathway for ammonium assimilation in Candida albicans and that this pathway is also significant in other Candida species. PMID- 2575655 TI - The effects of temperature on growth and production of the antibiotic granaticin by a thermotolerant streptomycete. AB - The synthesis of granaticin, a polyketide-derived antibiotic synthesized as a secondary metabolite by Streptomyces thermoviolaceus strain NCIB 10076, was studied at different growth temperatures. Quantitative measurements of the antibiotic made during batch fermentations showed that the yield was greatest at 45 degrees C, whereas the rate of synthesis was most rapid at 37 degrees C. The timing of the appearance of granaticin in culture could not be assigned to any particular phase of growth or to de-repression due to depletion of any particular nutrient. However, at all temperatures, appearance of the antibiotic coincided with a rise in ammoniacal nitrogen presumably due to deamination of glutamate, the carbon source for growth. We have previously shown that production of the antibiotic is pH sensitive and that some carbon sources result in higher titres than others. This paper examines the effect of temperature on the physiology of growth and on antibiotic production in more detail under conditions that also allow an exact measurement of granaticin yield. PMID- 2575656 TI - DNA polymorphism among isolates from multiple sites of a patient with chronic herpes simplex virus, type 1 infection. AB - DNA polymorphisms among independent isolates of herpes simplex virus (HSV) type 1 were studied from a 7-year-old male patient with recurrent infections of the skin and internal organs. In the patient's serum, HSV antibodies could not be detected by complement fixation, enzyme-linked immunosorbent assay (ELISA), or neutralization tests. ELISA tests for the presence of antibodies to human immunodeficiency virus were also negative. One HSV isolate was obtained from mesenteric nodes biopsied in 1983; one from skin in 1984; and three (postmortem) from brain, lungs, and liver in 1985. Restriction enzymes Eco RI, Bgl II, Hind III, Kpn I, and Bam H1 digestion patterns of the five isolates were similar. However, Sal I digests of isolates from skin, mesenteric nodes, lungs, and liver showed variations that were distinct from that of the brain isolate. Although Sal I digests of skin, mesenteric nodes, lungs, and liver isolates share a common variation in lacking F and G, the liver isolate can be further differentiated because of the gain of a restriction site on the H fragment. Thus, the three distinct variants observed were the isolates from brain (variant 1); from skin, mesenteric nodes, and lungs (variant 2); and from liver (variant 3). The fragments involved in variations among these isolates (presence or absence of Sal, G and H) are from the unique short and long regions (invariable regions) of the genome and therefore do not show heterogeneity in size. The extent of variation among these isolates is less than that seen among epidemiologically unrelated strains, suggesting that they originated from a single infecting strain, probably the brain isolate. PMID- 2575657 TI - Are mosquitoes gourmet or gourmand? AB - The scientific contributions of Professor Brian Hocking are summarized, especially his writings on the specificity of blood feeding. Mosquito host seeking behavior and feeding success are discussed within the context of human pest and vector species and in light of anticipated social and environmental changes. PMID- 2575658 TI - Review of new Nearctic mosquito distributional records north of Mexico, with notes on additions and taxonomic changes of the fauna, 1982-89. AB - During the past 7 years, 24 species of Nearctic mosquitoes have had extensions to their known distribution in the form of 32 new state and province records in the United States and Canada. They are included in this report along with relevant references. Additionally, 3 new United States country records have been established, 3 species have had name changes, a new species of Anopheles and sibling species of another anopheline have been described. Details of these occurrences are covered. PMID- 2575659 TI - Sampling, seasonal abundance, and mermithid parasitism of larval Coquillettidia perturbans in south-central Michigan. AB - Seasonal abundance of immature Coquillettidia perturbans was studied at 3 sites in south-central Michigan in 1987 and 1988. A modified boat bilge pump and funnel separators proved to be good sampling and sorting devices. Pupae were found in late May to early July, first and second instars were most abundant in July and August, while third and fourth instars were present year-round. Overall, larvae were most numerous in August and September, indicating that Cq. perturbans has a single generation per year in Michigan, with midsummer to fall as the main period of larval development, and with third and fourth larval instars as overwintering stages. Parasitism of Cq. perturbans larvae by a previously undiscovered mermithid nematode was documented at 2 sites in late summer. PMID- 2575660 TI - An improved semi-micro manipulator for precise injection into mosquito larvae. PMID- 2575661 TI - The effect of beta-blockade and angiotensin converting enzyme inhibition on kidney function in diabetic nephropathy. AB - Diabetic nephropathy is characterized by persistent albuminuria, a decline in glomerular filtration rate (GFR) and elevated blood pressure. About 40% of all insulin-dependent diabetic patients will develop nephropathy, thus increasing their morbidity and mortality. The effect of early aggressive antihypertensive treatment with metoprolol, frusemide or thiazide in insulin-dependent diabetic patients with nephropathy has shown a significant reduction in albuminuria and in the rate of decline in the GFR (from 0.94 to 0.29 and 0.10 ml/min per month over 72 months of antihypertensive treatment). The effect of angiotensin converting enzyme (ACE) inhibition on kidney function in diabetic nephropathy showed that the GFR is not dependent on angiotensin II (Ang II), and that ACE inhibition diminished albuminuria, probably by lowering glomerular hypertension. In conclusion, antihypertensive treatment with ACE inhibitors or beta-blockers combined with a diuretic protects kidney function and reduces albuminuria in diabetic nephropathy. Angiotensin converting enzyme inhibitors can be considered as first-line drugs for hypertensive patients with diabetic nephropathy. PMID- 2575662 TI - Oklahoma blood center to study human retroviruses in donors. PMID- 2575663 TI - Pharmacokinetics of an antiallergic agent, 1-(2-ethoxyethyl)-2-(hexahydro-4 methyl-1H-1, 4-diazepin-1-yl)-1H-benzimidazole difumarate (KG-2413) after oral administration: interspecies differences in rats, guinea pigs and dogs. AB - The pharmacokinetics of an antiallergic agent, 1-(2-ethoxyethyl)-2-(hexahydro-4 methyl-1H-1, 4-diazepin-1-yl)-1H-benzimidazole difumarate (KG-2413) after oral administration were studied in rats, guinea pigs and dogs. Maximum plasma level (Cmax) appeared at 23, 32 and 51 min after dosing in rats, guinea pigs and dogs, respectively. Plasma half-lives of the terminal phase were comparable to those after intravenous administration in each animal species. Pronounced interspecies differences were observed in the Cmax/dose and area under the plasma concentration-time curve (AUC)/dose, namely, these values were high in guinea pigs and low in rats and dogs. The extents of bioavailability were 0.036 in rats (20 mg/kg), 0.50 in guinea pigs (2 mg/kg) and 0.052 in dogs (2 mg/kg). These variations in the pharmacokinetic parameters in the animals were assumed to be mostly due to the species difference in the hepatic intrinsic clearance. PMID- 2575664 TI - Liquid chromatographic analysis of atenolol enantiomers in human plasma and urine. AB - A sensitive, stereospecific high-performance liquid chromatographic assay of atenolol (AT) enantiomers in human plasma and urine was developed. After addition of internal standard (IS, methoxamine) and alkalinization of the plasma, the drug and IS were extracted with ethyl acetate. The organic layer was evaporated and, after addition of saturated sodium carbonate, the residue was derivatized with ( )-menthyl chloroformate at ambient temperature; the reaction was complete within 30 s, with an efficiency of 97.2 +/- 2.6%. The diastereomeric derivatives of AT and IS were then extracted into chloroform and analyzed on a C18 column with a mobile phase consisting of water: acetonitrile: methanol. The samples were detected utilizing a fluorescent detector. Water-diluted urine samples were derivatized directly and then subjected to the same procedure as plasma. Under these conditions, AT diastereomers were separated with a resolution factor of 1.94, free of any interfering peak. An excellent linear relationship (r greater than or equal to 0.998) was obtained between the peak area ratios and the corresponding concentrations in the ranges 12.5-250 and 250-2500 ng/mL for plasma and urine, respectively. The applicability of the method is demonstrated by analysis of plasma and urine concentrations of individual enantiomers of AT after oral administration of a single 100-mg dose to a healthy subject. PMID- 2575665 TI - A study of synchronization of quantal transmitter release from mammalian motor endings by the use of botulinal toxins type A and D. AB - 1. The effects of botulinum toxin (BoTx) types A and D on spontaneous and evoked phasic transmitter release were studied in the isolated extensor digitorum longus muscle of the rat or the levator auris longus muscle of mice. 2. The toxins were injected subcutaneously into the hindleg of adult rats or the dorsal aspect of the neck of mice. At various times after the injection the muscles were removed from the anaesthetized animal and neuromuscular transmission examined in vitro by conventional intracellular techniques. 3. Both toxins reduced spontaneous transmitter release recorded as the frequency of miniature end-plate potentials but BoTx type D was less effective in that respect than the type A toxin. 4. With both toxins the block of evoked phasic transmitter release, recorded as end-plate potentials, was almost complete. As previously reviewed by Simpson (1986) the block produced by BoTx type A was partially reversed by procedures which elevate the intraterminal level of calcium ions. However, in BoTx type D-paralysed muscles such procedures failed to restore phasic transmitter release but caused a period of high-frequency asynchronous transmitter release following each nerve impulse. 5. To investigate if the lack of synchronization of evoked transmitter release observed in BoTx type D-paralysed muscles was due to alterations in presynaptic currents we examined, by perineural recordings, the Na+, fast K+, slow K+, K+-Ca2+-dependent and the Ca2+ currents in BoTx type D-paralysed muscles. These presynaptic currents were not altered as compared to unpoisoned controls. 6. We suggest that there exists a presynaptic process, which in addition to Ca2+ influx participates in transmitter synchronization and which is a main target for BoTx type D action. PMID- 2575667 TI - Genetic heterogeneity and mitochondrial DNA heteroplasmy in Leber's hereditary optic neuropathy. AB - Analysis of mitochondrial DNA from patients with Leber's hereditary optic neuropathy and their relatives showed that the previously reported mutation at base pair (bp) 11778, shown by loss of a recognition site for the restriction endonuclease SfaNI, was present in only four out of eight families. This mutation was associated with a poor prognosis for visual recovery, whereas four of five affected males without the 11778 bp mutation followed for four years or more had regained useful vision. All but one of the subjects showing the SfaNI site loss had a variable mixture of mutant and normal mitochondrial DNA in peripheral blood, and the relative proportions appeared to be correlated with the risk of developing or transmitting Leber's hereditary optic neuropathy. PMID- 2575666 TI - The electrophysiological effects of neurotensin on neurones of guinea-pig prevertebral sympathetic ganglia. AB - 1. The membrane effects of neurotensin on neurons of guinea-pig prevertebral ganglia were investigated by means of intracellular recording techniques in vitro. 2. Neurotensin (2-5 microM) applied by superfusion caused depolarizing responses in fifty-seven of seventy-four neurones tested in the inferior mesenteric ganglion and thirty-seven of forty-seven neurones tested in the coeliac plexus. The remaining neurones tested showed no membrane response. 3. Responses to neurotensin could be discriminated into two different types of membrane depolarizations on the basis of their different time courses and pharmacological characteristics: a steady-state type of depolarization and a transient type of depolarization. Seven of fifty-seven responsive neurones tested in the inferior mesenteric ganglion and ten of thirty-seven responsive neurones tested in the coeliac plexus responded to neurotensin with a depolarization which was maintained constant as long as neurotensin was superfused over the preparation (steady-state type). Forty-eight of fifty-seven responsive neurones tested in the inferior mesenteric ganglion and twenty of thirty-seven responsive neurones tested in the coeliac plexus responded with a transient depolarization which was followed by a repolarization in the maintained presence of neurotensin (transient type). A combination of both types of responses was observed in two neurones tested in the inferior mesenteric ganglion and in seven neurones tested in the coeliac plexus. 4. Steady-state type responses were characterized by a slowly developing membrane depolarization which reached a plateau and lasted throughout the presence of neurotensin. Amplitude and time course of this response were not altered in a solution containing hexamethonium (10 microM) and atropine (10 microM) or by a solution low in calcium (1 mM) and high in magnesium (15 mM). 5. Transient type depolarizations evoked by neurotensin were faster in reaching their maximum and were followed by a repolarization during the maintained presence of neurotensin. Responses similar in time course and amplitude were obtained in solutions containing hexamethonium (10-100 microM) and atropine (10 microM). However, transient responses were abolished in a solution low in calcium (1 mM) and high in magnesium (15 mM) and were markedly attenuated in ganglia treated with capsaicin (3 microM). 6. Both types of depolarizations were associated with increases in membrane input resistance. Both responses converted subthreshold depolarizing electrotonic potentials and subthreshold fast EPSPs to action potentials. 7. Both types of depolarizations were observed when the C-terminal hexapeptide fragment neurotensin 8-13 was used.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2575669 TI - Presymptomatic detection and prenatal diagnosis for myotonic dystrophy by means of linked DNA markers. AB - The close genetic linkage between the loci for apolipoprotein CII (ApoCII) and myotonic dystrophy makes presymptomatic detection and prenatal diagnosis feasible. We report three years' service experience of providing presymptomatic detection and prenatal diagnosis for myotonic dystrophy in 99 families. Careful clinical study of older family members remains important. The introduction of new probes (CKMM and BCL4) has helped to solve the problem of uninformativeness owing to unhelpful genotype distribution in a family. Nevertheless, informativeness cannot be guaranteed and families should be studied before pregnancy is undertaken whenever possible. Presymptomatic testing and prenatal diagnosis for myotonic dystrophy are soundly based. All affected subjects should have DNA banked for future use when other family members may require genotype information. PMID- 2575668 TI - Genetic studies on a new deficiency gene (PI*Ztun) at the PI locus. AB - During a study of the alpha 1 antitrypsin (AAT) protein and its locus (PI) by high resolution isoelectric focusing and direct molecular analysis of 106 PIZ probands and their families, a new allele (Ztun) was identified that resembles Z in many of its properties. Two sibs, both compound heterozygotes for Ztun and Z, showed similar evidence of mild liver involvement that was indistinguishable from that associated with classical ZZ homozygotes. The Ztun protein appeared to be deficient in the plasma to about the same degree as the Z protein. Allele specific oligonucleotide analysis of amplified genomic DNA indicated that the new allele is the result of a mutation in exon V that is identical to the classical G ---A transition at codon 342 that results in the Glu----Lys substitution characteristic of the Z allele. An analysis of DNA haplotypes constructed from polymorphic restriction enzyme recognition sites in and around the PI locus confirmed that Ztun probably represents a new mutation at codon 342 that has occurred on an M2-like genetic background. PMID- 2575670 TI - Misdiagnosed normal fetus owing to undetected germinal mosaicism for DMD deletion. PMID- 2575671 TI - Effects on intestinal nutrient uptake and brush border membrane enzymes in response to atherogenic diet in rhesus monkeys. AB - Transport of nutrients and kinetic parameters (Vmax and Km) of brush border membrane (BBM) enzymes were studied in duodenum, jejunum, and ileum from atherogenic diet-fed monkeys. The Km remained unaltered while feeding of atherogenic diet resulted in higher Vmax of sucrase, maltase, and alkaline phosphatase and lower Vmax of gamma-glutamyltranspeptidase and leucine aminopeptidase compared to controls. Na+-dependent D-glucose transport was higher in duodenum and jejunum and unaltered in ileum. In contrast to D-glucose transport, the transport of amino acids was decreased in all three intestinal segments from atherogenic diet-fed monkeys. PMID- 2575672 TI - Glutamine synthetase II in Rhizobium: reexamination of the proposed horizontal transfer of DNA from eukaryotes to prokaryotes. AB - We have determined the DNA sequence of a Rhizobium meliloti gene that encodes glutamine synthetase II (GSII). The deduced amino acid sequence was compared to that of Bradyrhizobium japonicum GSII and those of various plant and mammalian glutamine synthetases (GS) in order to evaluate a proposal that the gene for this enzyme was recently transferred from plants to their symbiotic bacteria. There is 83.6% identity between the R. meliloti and B. japonicum proteins. The bacterial GSII proteins average 42.5% identity with the plant GS proteins and 41.8% identity with their mammalian counterparts. The plant proteins average 53.7% identity with the mammalian proteins. Thus, the GS proteins are highly conserved and the divergence of these proteins is proportional to the phylogenetic divergence of the organisms from which the sequences were determined. No transfer of genes across large taxonomic gaps is needed to explain the presence of GSII in these bacteria. PMID- 2575674 TI - [Liver mitochondrial respiration during hyperthermia]. AB - The influence of hyperthermia on liver mitochondrial respiration and liver metabolites levels was studied by increasing body temperature to 41.0 degrees C in rats under oxygen and nitrous oxide anesthesia maintaining constant PaCo2. At 41.0 degrees C, the increase in ATP and energy charge level (EC) by Atkinson and the increase of state 3 and RCR in NADH linked substrate were observed. After maintaining body temperature at 41.0 degrees C for 30 minutes, the decrease in ATP, EC, state 3, RCR and ADP/O were observed. The degree of change from 38.0 degrees C to 41.0 degrees C in state 3, state 4, RCR and ADP/O was greater in NADH linked substrate than in non-NADH one. After keeping body temperature at 38.0 degrees C for 30 minutes by the whole body cooling, the recovery of EC, state 3 and RCR was observed. The effects of cooling with drugs (dantrolen or methyl-prednisolone) had no consistent effect. These findings suggest that the hyperthermic stress on mitochondrial respiration is focused on complex I in electron transport system. PMID- 2575673 TI - Cardiovascular effects of detomidine, a new alpha 2-adrenoceptor agonist, in the conscious pony. AB - The cardiovascular effects of detomidine and xylazine were compared in six chronically instrumented, conscious ponies. Ponies were instrumented with a micromanometer in the left ventricular chamber, a Doppler flow probe on a coronary artery and sonomicrometer crystals in the left ventricular free wall. Heart rate, ventricular systolic pressure, stroke work, dP/dtmax, minute work and coronary blood flow were measured for 4 h following intravenous injection of detomidine at several doses or xylazine at 1.1 mg/kg. Both drugs caused a profound hypertensive response at 15 s post-injection. The magnitude of the pressure change did not increase with detomidine doses greater than 20 micrograms/kg. There was a dose-dependent effect on the duration of the hypertension. Bradycardia and A-V blockade of similar magnitude followed the hypertension at all drug doses. Both drugs caused a negative inotropic effect on the heart at all doses. Minute work, a mechanical index of myocardial O2 demand, and coronary flow decreased to a similar extent following all drug treatments. With the exception of a greater hypertensive response, detomidine at the dosages studied, produced cardiovascular effects that were very similar to those of the recommended dosage of xylazine. PMID- 2575675 TI - [APRT deficiency in Japanese]. PMID- 2575676 TI - [Close correlation between restriction fragment length polymorphism of the L-myc gene and metastasis of lung cancer and prognosis]. PMID- 2575677 TI - [Serum diagnosis of cancer with monoclonal antibodies]. PMID- 2575678 TI - [Characteristics of gamma glutamyl transferase in melanoma]. AB - Gamma glutamyl transferase (GGT) is widely distributed in mammalian tissues, and its biological heterogeneity has been demonstrated among various tissues. In order to investigate the biological characteristics of GGT in melanomas, enzyme histochemical and biochemical studies were performed using amelanotic/melanotic and murine/human melanomas as materials. Enzyme-histochemically, GGT activity appeared to be present only in melanogenic cells in vitro. Biochemical assays of tissue extracts revealed that the specific activity was much higher in melanotic melanomas than in amelanotic. In addition, analysis of GGT-isoenzymes demonstrated that an isoenzyme band at approximately 110KD was expressed in tumorigenic or highly-metastatic tissues. These findings suggest that GGT in melanoma is closely related to the ability of melanin production and that the possible existence of a unique isoenzyme may reflect the intensity of tumorigenic and/or metastasis. PMID- 2575679 TI - Changes in release of N-acetyl-beta-D-glucosaminidase, gamma-glutamyl transpeptidase and leucine aminopeptidase from renal tubular cells under anaerobic conditions. AB - Although the urinary excretion of NAG and gamma-GTP has been employed as an index of renal injury, the mechanism of release of these enzymes remains unclear. In the case of renal ischemic injury, we recently reported that u-NAG and u-gamma GTP were not correlated well with the degree of renal damage especially in the late phase of ischemic injury [1]. In order to elucidate the relationship between release of these enzymes and renal ischemic injury, we devised an in vitro model of anoxic injuries to renal tubular cells and measured the time-course release of NAG (a lysosomal enzyme), gamma-GTP and LAP (brush border enzymes) at 37 degrees C under five different aerobic and anaerobic conditions (95% O2, 20% O2, 10% O2, 3% O2 and 0% O2). The ATP and lactate levels in the system were also measured to estimate the metabolic state of the tubular cells. In the 3% O2, 10% O2 and 20% O2 groups, NAG, gamma-GTP and LAP were released into the media at a similar rate to that in the 95% O2 group, and anaerobic damage to the renal tubular cells was not observed. In the 0% O2 group, the NAG in the medium increased from 60 to 180 min at a significantly higher rate than that of the 95% O2 group, and a linear relationship was observed between NAG concentration and incubation time (r = 0.73), although NAG did not increase significantly at 30 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575680 TI - [Clinical evaluation of serum sialyl Lewis X-i (SLX) in diffuse panbronchiolitis]. AB - Clinical comparison of SLX with other tumor-associated antigens such as CA19-9, CA125, and CEA, was made in benign respiratory diseases including diffuse panbronchiolitis (DPB), bronchiectasis (BE), bronchial asthma (BA), and pulmonary emphysema (PE). Sensitivities of each marker (greater than 38.0 U/ml) on DPB were 79.4% in SLX, 68.0% in CA19-1, 46.7% in CA125, and 35.7% in CEA. Serum levels of SLX in DPB and BE were significantly higher than those in BA and PE. There seemed to be no relationship between serum levels of SLX and CRP, ESR, and the volume of sputum. Immunohistochemical studies showed positive staining on the surface of respiratory bronchioles and alveolar walls in DPB and these findings were not observed in normal lung tissues. We consider that the high value of serum levels of SLX in DPB can be explained by these findings. PMID- 2575681 TI - [Comparison of carbohydrate antigens--sialylated Lewisx and sialylated SSEA-1 in the sera from patients with primary lung cancer]. AB - Serum levels of sialylated Lewisx (SLEX) and sialylated SSEA-1 (S-Xi) in 136 cases of diagnosed lung cancer (63 adenocarcinoma, 45 squamous cell carcinoma, 20 small cell carcinoma and 8 large cell carcinoma) and 111 cases of benign pulmonary disease were measured. The positive rate of these markers in the primary lung cancer group was significantly higher than those in benign pulmonary diseases. The positive rates of serum SLEX and S-Xi in all lung cancer cases were 27.2% and 27.9%, respectively. The antigen levels in the sera were higher in adenocarcinoma as compared to other histologic types, and increased as the stage advanced. It was concluded that SLEX and S-Xi are very useful markers of lung cancer for diagnosis and monitoring the clinical status. PMID- 2575682 TI - [Changes in the platelet-vascular system of hemostasis in patients with ischemic heart disease and hypertension after the treatment]. AB - The status of platelet aggregability, cyclic nucleotides and the thromboxane prostacyclin system was examined in 40 patients with Functional Class II-III angina pectoris treated with perdipine, a calcium antagonist, and in 40 patients with Stage II hypertensive disease treated with tenolol, a beta-adrenoblocker. The therapy was found to modify the initially abnormal parameters of platelet vessel hemostasis both in coronary heart disease and hypertension. When the initial parameters of platelet functional activity were normal, the treatment with perdipine and tenolol caused no noticeable changes. PMID- 2575683 TI - [Drugs in secondary prevention of ischemic heart disease: achievements, problems and prospects]. AB - The paper provides critical reviews of the progress made in the past 25 years in studies on long-term drug prophylaxis of coronary heart disease. Particular attention is given to general problems, including those in the application of three major groups of antianginal agents, namely, nitrates, beta-adrenoblockers, and calcium antagonists to the prolonged secondary prevention of the disease. It has been shown that there is every prospects of future studies in this area. A general conclusion is drawn from a number of investigations performed at the Preventive Pharmacological Department, All-Union Cardiology Research Center, and in the All-Union Research Center of Preventive Medicine, USSR Ministry of Health over the past 5 years. These involve methodologically complicated matters of choice and long-term usage of drugs, including antianginal drugs within the collaborative studies. PMID- 2575684 TI - [Successful replantation of the foot in a child]. PMID- 2575685 TI - [Thermometry as a method of evaluating the status of the peripheral sympathetic nervous system in patients with hemorrhagic fever with nephrotic syndrome]. AB - The inference on irritation of sympathetic nervous system and predominant location of the the process in the thoracic and iliac parts of the sympathetic chain is drawn from investigation of skin temperature at various sites of the body and catecholamines excretion in 30 patients with hemorrhagic fever and renal syndrome. Norepinephrine, excretion enhancement and changes in the picture of skin temperatures were the underlying evidence. PMID- 2575686 TI - [Reflections on a trip to Korea. At the 19. Congress of the International Council of Nurses, May 28-June 2, 1989 in Seoul/South Korea]. PMID- 2575687 TI - [Current aspects of stress ulcer prevention]. PMID- 2575688 TI - Molecular analysis of Japanese Gaucher disease. PMID- 2575689 TI - 3-Ketothiolase deficiency: heterogeneity in a defect of mitochondrial acetoacetyl CoA thiolase biosynthesis in fibroblasts from four patients. PMID- 2575691 TI - Biochemical studies on ghalakinoside, a possible antitumor agent from Pergularia tomentosa. PMID- 2575690 TI - Effects of cryptolepine alone and in combination with dipyridamole on a mouse model of arterial thrombosis. AB - The effects of cryptolepine alone and in combination with other antiplatelet agents have been investigated using a mouse model of arterial thrombosis. Intraperitoneal premedication with crytolepine produced 25% maximal protection at 1 mg/kg while dipyridamole producedd a 20% maximal effect at 2 mg/kg. Higher doses of cryptolepine showed a reduced effect. In contrast, indomethacin and aspirin produced a dose-related and higher degree of protection. A combination of cryptolepine and dipyridamole was more effective than when the individual drugs were used alone. The use of 20% ethanol as a dosage vehicle enhanced the protective effects of all drugs tested and the ethanol vehicle alone provided 45% protection. PMID- 2575692 TI - [Benzodiazepine antagonists in the treatment of heptic encephalopathy]. AB - For the first time a causal treatment of hepatic encephalopathy may be possible by the benzodiazepine antagonist flumazenil. In contrast to all other treatments used so far by flumazenil hepatic encephalopathy improves within minutes. Flumazenil is the first benzodiazepine antagonist which can be used in humans and is a well established for treatment of benzodiazepine overdose. For treatment of hepatic encephalopathy development of a new antagonist with a longer half-life is desirable. However, ut should be stressed that the current experience with flumazenil is limited and that the effects of flumazenil on hepatic encephalopathy is not proven by randomized controlled studies. Therefore, this drug should only be used in clinical studies. PMID- 2575693 TI - [Helicobacter pylori-induced cost-benefit risk considerations]. PMID- 2575694 TI - Caffeine and regional brain monoamine utilization in mice. AB - Caffeine (100 and 200 mg/kg, 30 min., i.p.) selectively altered the regional utilization of monoamines in the brains of mice. This depended upon the specific neurotransmitter and metabolite studied. Caffeine increased serotonin (5HT) utilization a dramatic ten-fold in the OB but decreased 5HT utilization in the HT. No 5HT changes were seen in other brain regions. Caffeine markedly increased norepinephrine (NE) utilization in the olfactory bulbs (OB), olfactory tubercles (OT), prefrontal cortex (PC), amygdala (AMY), hypothalamus (HT) and hippocampus (HC). Caffeine increased dopamine (DA) utilization in the OB, OT, PC, septum (SP), HT and thalamus (TH) but by various metabolic routes. The selective regional alterations in monoamine utilization produced by caffeine may be relevant to caffeine's central stimulatory effects. Limbic structures are predominantly involved. These changes may have important clinical and research implications. For example, the profound effect of caffeine on OB monoamines indicates that it may serve as a meaningful tool in olfactory research, including the bulbectomy model. Caffeine may also be useful in other limbic system behavioral models. PMID- 2575695 TI - Isolation of a rat adrenal cDNA clone encoding phenylethanolamine N methyltransferase and cold-induced alterations in adrenal PNMT mRNA and protein. AB - Cold stress is known to increase the synthesis and release of catecholamines in the sympathoadrenal system. Previously, we have demonstrated that cold exposure results in a 3- to 4-fold increase in adrenomedullary tyrosine hydroxylase (TH) activity, which is mediated by concomitant alterations in TH mRNA and protein levels. To further investigate the effects of stress on the expression of the catecholamine biosynthetic enzymes, we have isolated a rat cDNA clone encoding the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT). The cDNA clone is 905 nucleotides in length and contains a single open reading frame corresponding to 270 amino acids. The amino acid sequence predicted from this nearly full-length cDNA is 89% and 86% identical to that of bovine and human PNMT, respectively. Using the rat PNMT cDNA as a hybridization probe, we have measured the effects of cold stress on the relative abundance of adrenomedullary PNMT mRNA. Levels of PNMT protein were also estimated using an immunoblot analysis. As in the case of TH, cold exposure resulted in a rapid and prolonged increase in PNMT mRNA abundance, followed by concomitant increases in PNMT immunoreactivity. However, there appear to be quantitative and qualitative differences in the adaptive response of TH and PNMT to cold stress. PMID- 2575697 TI - [The role of the feldsher in propagandizing the optimal methods for regulating the birth rate]. PMID- 2575696 TI - The role of Ca2+ channels of the L-type in neurotransmitter plasticity of cultured sympathetic neurons. AB - We have studied the effects of Ca2+ antagonists and agonists on the development of choline acetyltransferase (ChAT), tyrosine hydroxylase (TOH) and acetylcholinesterase (AChE) in cultures of rat sympathetic neurons maintained for 6-9 days in low K+ (5 mM) or high K+ (35 mM) medium. Previous experiments have shown that high K+ medium increases TOH activity and TOH-mRNA level up to 3.5 fold and depresses the development of AChE, in particular of its asymmetric A12 form. Moreover, high K+ medium inhibits ChAT induction by 90% in muscle conditioned medium (Raynaud et al., Dev. Biol., 119 (1987) 305-312; 121 (1987) 548-558). None of the Ca2+ antagonists tested affected the development of ChAT, TOH or AChE in low K+ medium. In high K+ medium, nitrendipine (3 microM) or fluspirilene (1 microM) fully restored ChAT induction by conditioned medium to the level observed in low K+ medium. Other drugs (1 microM) gave partial reversion: flunarizine greater than (+)-PN 200-110 greater than (-)-D-888 greater than cinnarizine = lidoflazine. On the other hand, ChAT induction was not restored by a calmodulin inhibitor, calmidazolium (1 microM). Fluspirilene, PN 200-110, and nitrendipine also totally abolished TOH induction by high K+ medium; fluspirilene (1 microM) suppressed the inhibitory effect of high K+ medium on AChE development and restored the development of A12 AChE. Conditioned medium also depresses AChE and blocks the development of A12 AChE (Swerts et al., Dev. Biol., 103 (1984) 230-234), but these effects were insensitive to fluspirilene. The Ca2+ agonist Bay K 8644 (1 microM) potentiated the effects of elevated K+ on both ChAT and TOH. The data suggest that the effects of long-term depolarization on ChAT, TOH and AChE are mediated by Ca2+ entry specifically through voltage sensitive channels of the L-type. Our results on cultured sympathetic neurons raise the possibility that Ca2+ antagonists, which are widely used clinically, may affect the expression of neurotransmitter phenotypic traits in vivo and interfere with trans-synaptic induction of enzymes. PMID- 2575698 TI - [The work of a rural district drug abuse office (from the work experience of the drug abuse office of Belgorod District)]. PMID- 2575699 TI - Restriction-map variation associated with the G6PD polymorphism in natural populations of Drosophila melanogaster. AB - Restriction-map variation was studied in 126 copies of the G6pd region in X chromosome lines of Drosophila melanogaster from North America, Europe, and Africa. Special attention was focused on the distribution of variation relative to the geographically variable polymorphism for two electrophoretic variants. Nucleotide heterozygosity as determined by eight six-cutter restriction enzymes for the 13-kb region is estimated, on the basis of the worldwide sample, to be 0.065%, which is the lowest value reported for any comparable region in the D. melanogaster genome. Significant linkage disequilibrium between electrophoretic alleles and restriction-site variation is observed for several sites. In contrast to published studies of other genetic regions, there are large insertions that reach significant frequencies and are found across considerable geographic distances. There is a clustering of this variation inside the first large intervening sequence of the G6PD gene. PMID- 2575700 TI - Genetic activity of a trans-regulatory locus in hepatoma hybrid cells. AB - Tissue-specific extinguisher-1 (TSE1) is a genetic locus on mouse chromosome 11 that can repress expression of several liver genes in trans. The activity of this locus is apparent in rat hepatoma microcell hybrids that retain chromosome 11 from mouse fibroblasts: such hybrids fail to accumulate particular hepatic mRNAs, including those encoding tyrosine aminotransferase (TAT) and phosphoenolpyruvate carboxykinase (PEPCK). In this report, we show that TSE1 from a TAT-, PEPCK- mouse hepatoma cell line expressing a fetal liver phenotype also induced TAT and PEPCK extinction when transferred into rat hepatoma recipients. Thus, TSE1 appears to be active in TAT-, PEPCK- cells of both hepatic and non-hepatic lineages. This suggests that TSE1 may play a role in the developmental regulation of hepatic gene expression in the liver. PMID- 2575702 TI - CRP/cAMP- and CytR-regulated promoters in Escherichia coli K12: the cdd promoter. AB - Transcriptional regulation of the deoP2 promoter by the cyclic AMP/cyclic AMP receptor protein complex (cAMP/CRP) and the CytR repressor requires two high affinity CRP targets located around -41 and -93 bp preceding the start site for transcription. Here we report the structure of cddP, another CRP/CytR-regulated promoter. In common with what was found in deo, the cdd promoter also contains multiple CRP targets. Thus, using the DNasel footprinting procedure, tandem CRP binding sites were identified around -41 and -93. These findings support a general model for CytR binding and CytR regulation, in which (i) CytR and the CRP/cAMP complex bind to similar or identical targets, (ii) two or more targets are necessary for proper binding of CytR to a promoter region, and (iii) CytR represses transcription by antagonizing cAMP/CRP activation. PMID- 2575701 TI - Structural and functional analysis of the mini-circle, a transposable element of Streptomyces coelicolor A3(2). AB - The mini-circle is a transposable element which is present in Streptomyces coelicolor A3(2) in both free circular and chromosomally integrated linear forms. The nucleotide sequences of the mini-circle and its preferred site of integration in the Streptomyces lividans TK64 chromosome were determined. Three putative open reading frames were identified in the mini-circle sequence. The mini-circle does not appear to cause a target site duplication on transposition and does not have perfect terminal inverted repeats. The observed site-specificity of the mini circle is not mediated by extensive homology between the element and the chromosomal integration site. Transposition of the mini-circle into the S. lividans chromosome was demonstrated and found to be some two orders of magnitude less efficient than integration of the circular form of the element, suggesting that the circular form of the mini-circle might be a normal intermediate in the transposition process. PMID- 2575703 TI - Molecular characterization of a gene from Saccharopolyspora erythraea (Streptomyces erythraeus) which is involved in erythromycin biosynthesis. AB - A 7.3 kbp DNA fragment, encompassing the erythromycin (Em) resistance gene (ermE) and a portion of the gene cluster encoding the biosynthetic genes for erythromycin biosynthesis in Saccharopolyspora erythraea (formerly Streptomyces erythraeus) has been cloned in Streptomyces lividans using the plasmid vector pIJ702, and its nucleotide sequence has been determined using a modified dideoxy chain-termination procedure. In particular, we have examined the region immediately 5' of the resistance determinant, where the tandem promoters for ermE overlap the promoters for a divergently transcribed coding sequence (ORF). Disruption of this ORF using an integrational pIJ702-based plasmid vector gave mutants which were specifically blocked in erythromycin biosynthesis, and which accumulated 3-O-alpha-L-mycarosylerythronolide B: this behaviour is identical to that of previously described eryC1 mutants. The eryC1-gene product, a protein of subunit Mr 39,200, is therefore involved either as a structural or as a regulatory gene in the formation of the deoxyamino-sugar desosamine or in its attachment to the macrolide ring. PMID- 2575704 TI - Upstream activating sequences that are shared by two divergently transcribed operons mediate cAMP-CRP regulation of pilus-adhesin in Escherichia coli. AB - Transcription of the genes encoding pilus-adhesin of serotype F13 in digalactoside-binding Escherichia coli required activation by the cAMP-CRP complex. Analysis of protein-DNA interaction in vitro showed that CRP bound in a cAMP-dependent manner to a sequence located 0.2 kb upstream of the point of transcription initiation of the pilus subunit operon. The cAMP-CRP activation included, in addition to the main pilus operon, the oppositely oriented operon encoding the Papl regulatory protein. Furthermore, the auto-regulatory product of the promoter-proximal gene (papB) in the pilus subunit operon was found to stimulate the papl transcriptional unit. Thus the cAMP-CRP complex and PapB might act in concert and indirectly promote pili synthesis by stimulating expression of the Papl positive regulator. The results of trans-complementation experiments and analyses using lacZ operon fusion derivatives showed that the cAMP-CRP activation also operated directly in cis on the pilus subunit operon. The region containing the CRP binding site appeared to function as an upstream activating sequence since deletion abolished expression even when the pap regulatory proteins Papl and PapB were supplied in trans. The implications for possible mechanisms of transcriptional activation by the cAMP-CRP complex at this novel location between the two oppositely oriented operons are discussed. PMID- 2575705 TI - Myosin heavy chain gene amplification as a suppressor mutation in Caenorhabditis elegans. AB - In the nematode, Caenorhabditis elegans, the body wall muscles contain paramyosin and two different types of myosin heavy chain, MHC A and MHC B. In mutants that do not express MHC B or that express defective paramyosin, muscle structure is disrupted and movement is impaired. Second site mutations in the sup-3 locus partially reverse these defects and are correlated with a 2- to 3-fold increase in the accumulation of the MHC A isoform. The sup-3 mutations occur at a high frequency (10(-4] after ethyl methanesulfonate (EMS) mutagenesis. This is comparable to the average EMS-induced mutation rate per gene in C. elegans. In this paper we show that the sup-3 mutation is an amplification of the structural gene for the MHC A protein, myo-3. We employed genomic Southern hybridization with MHC gene-specific probes in order to measure the copy number of the myo-3 gene relative to that of the MHC B gene, unc-54. We have identified the putative amplification junctions for these sup-3 alleles using a set of cosmid clones which encompass myo-3 region. Although it has been suggested that gene amplification plays an important role in evolution, there are few known cases of gene amplification in the germ line cells of multicellular organisms. The results shown here provide a clear example of a heritable gene amplification event that occurs at a high frequency in the germ line. Similar events may thus represent the initial event in the evolution of new function and in the formation of multigene families. PMID- 2575706 TI - Transformation by integration in Podospora anserina. III. Replacement of a chromosome segment by a two-step process. AB - We have developed in Podospora anserina a two-step procedure for DNA sequence replacement through transformation which might be applicable to other filamentous fungi. Targeting of transforming DNAs to their homologous locus is achieved provided a cosmid vector is used. Southern blot analysis of genomic DNAs from a set of transformants is presented. The data confirm that cosmids integrate into the chromosome through mostly homologous recombination which leads to a duplicated sequence separated by the vector. This event was found to be unstable in crosses. We show that this instability is due to the frequent excision of the vector together with the selective marker and one copy of the duplication, either the resident or foreign sequence. The two sequences can be distinguished because they exhibit restriction fragment length polymorphism. Therefore, Podospora anserina treats duplications occurring through transformation in a way differing from that exhibited by Neurospora crassa and Ascobolus immersus. PMID- 2575707 TI - Use of a DNA probe to analyse the dynamics of infection with rodent malaria parasites confirms that parasite clearance during crisis is predominantly strain- and species-specific. AB - A DNA probe, PCsv4.1, isolated from Plasmodium chabaudi chabaudi AS, generates in Southern blotting experiments restriction fragment length polymorphisms specific to a particular rodent malaria parasite line. It was used to develop an assay which allows identification and semi-quantitative compositional analysis of sample parasite populations in which one or more strains, subspecies or species were present. In experiments where mechanisms effecting parasite clearance during crisis were studied, the assay was used to determine the composition of parasite populations present in P. c. chabaudi AS infected mice challenged during crisis with homologous or heterologous parasites. It was thus confirmed that clearance mechanisms during crisis operate in a predominantly specific manner. PMID- 2575708 TI - Inhibition of N-methyl-D-aspartate (NMDA)- and L-glutamate-induced noradrenaline and acetylcholine release in the rat brain by ethanol. AB - The influence of ethanol on stimulation-evoked 3H-transmitter release was examined in slices of the rat brain cortex and corpus striatum preincubated with 3H-noradrenaline and 3H-choline, respectively. 3H-Transmitter release was stimulated by NMDA, L-glutamate, electrical impulses, reintroduction of Ca2+ ions ("Ca2(+)-evoked release", after superfusion with Ca2(+)-free, K(+)-rich solution) or veratridine. In cortical slices preincubated with 3H-noradrenaline and superfused with Mg2(+)-free, otherwise physiologically composed salt solution, ethanol inhibited the NMDA- or L-glutamate-induced tritium overflow (IC50 45 and 37 mmol/l, respectively). In contrast, the tritium overflow in response to electrical stimulation, reintroduction of Ca2+ ions or veratridine was not affected by ethanol at concentrations up to 320 mmol/l; these experiments were carried out in cortical slices superfused with solution containing a physiological Mg2+ concentration. Ethanol also failed to inhibit Ca2(+)-evoked release in the absence of Mg2+ ions. In the presence of 1 mumol/l veratridine, but not in its absence, NMDA induced tritium overflow even when cortical slices were superfused with salt solution containing a physiological Mg2+ concentration; again, ethanol inhibited this NMDA-evoked tritium overflow (IC50 73 mmol/l. In striatal slices preincubated with 3H-choline and superfused with Mg2(+)-free "physiological" salt solution the NMDA-evoked tritium overflow was also, although at lower potency, inhibited by ethanol (IC50 192 mmol/l). In spite of the differences between the IC50 values of ethanol determined for the inhibition of cortical noradrenaline and striatal acetylcholine release, it may be concluded that the NMDA receptor-ion channel complex is one of the sites of action underlying the ethanol-induced inhibition of neurotransmitter release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575709 TI - Inhibition by vecuronium of carbachol-induced influx of 22Na+, 45Ca2+ and secretion of catecholamines in cultured bovine adrenal medullary cells. AB - In cultured bovine adrenal medullary cells, vecuronium, pancuronium and D tubocurarine reduced carbachol-induced 45Ca2+ influx and catecholamine secretion by inhibiting 22Na+ influx via nicotinic receptor-ion channel complex with IC50 values of 0.43, 7.6 and 3.9 mumol/l, respectively. IC50 values of pancuronium and D-tubocurarine observed in adrenal medulla were one order of magnitude higher than the plasma concentrations of these muscle relaxants reported to produce 50% neuromuscular blockade, while IC50 of vecuronium was quite close between adrenal medulla and skeletal muscle. PMID- 2575710 TI - Dopamine D1 receptors labelled with [3H]SCH23390 in rabbit cerebral cortex and neostriatum. Equilibrium binding, kinetics and selectivity. AB - The binding characteristics of the novel benzazepine compound SCH23390 were studied using membrane preparations from rabbit cerebral cortex (CTX) and neostriatum (CPU; caudate putamen). The association kinetics of [3H]SCH23390 to membranes from CTX and CPU were rapid, while the dissociation kinetics were extremely slow and only around 40-60% of the binding was displaced two hours after the addition of either S(+)-butaclamol or 30 volumes of buffer. The saturation curves revealed that [3H]SCH23390 bound with high affinity in both tissues, with densities of 133 fmol/mg protein for CTX (Kd 25 degrees C = 0.31 nM) and 664 fmol/mg protein for CPU (Kd = 0.13 nM). the specificity of binding to the cortical D1 receptor was verified in competition experiments with a variety of dopaminergic agents. The rank order of potency of these compounds was consistent with the pharmacology of the dopaminergic D1 site. All competition curves were better fitted to a one-site model with Hill coefficients around one, indicating that [3H]SCH23390 was binding to a single cortical site. The stereoselectivity of the cortical [3H]SCH23390 binding site could be demonstrated by the use of enantiomer pairs of dopaminergic drugs. This study provides compelling evidence that [3H]SCH23390 binds to dopamine D1 receptors in the neostriatum and cerebral cortex of the rabbit. PMID- 2575711 TI - Dual action of clonidine on insulin release: suppression, but stimulation when alpha 2-adrenoceptors are blocked. AB - As shown previously clonidine reduces glucose-stimulated insulin release and this effect is mediated by inhibitory postsynaptic alpha 2-adrenoceptors. The present experiments demonstrate that clonidine has the additional property to also stimulate insulin release. This became evident when the alpha 2-adrenoceptors of isolated islets were blocked by benextramine, and thus protected from being stimulated by clonidine. In the presence of benextramine, clonidine no longer reduced, but on the contrary enhanced, the release of insulin in response to glucose. In control experiments benextramine by itself failed to affect insulin release from isolated islets. These results show that the imidazoline derivative clonidine shares the property of other imidazoline compounds to enhance the insulin response to glucose. All of these agents may stimulate insulin by binding to "imidazoline-preferring" sites, that clearly differ from alpha-adrenoceptors. PMID- 2575712 TI - Women's health: life lines. PMID- 2575714 TI - Electrophysiological responses of rat pituitary cells in somatotroph-enriched primary culture to human growth-hormone releasing factor. AB - The in vitro effects of human growth hormone releasing factor (hGRF, 1-44) were studied in somatotroph-enriched cultures (75-85%) obtained from adult male rat pituitaries. Cells perifused with hGRF showed an up to 800% increase in growth hormone (GH) release over basal values in a dose-dependent manner. Calcium current blockers (5 mM of Co2+, Ni2+ or Cd2+) completely inhibited this stimulating effect but sodium-free (choline) medium did not. Using a single intracellular-electrode recording technique, it was found that hGRF induced a dose-dependent depolarizing response concomitant with a decrease in membrane resistance in 38% of the cells recorded (98 of 258 cells). The reversal potential of this response was close to -40 mV. This depolarizing response was recorded in both excitable and unexcitable cells with no marked difference. Co2+ and Ni2+ (5 mM) completely and reversibly inhibited the membrane response to hGRF. Application of hGRF and somatostatin (SRIF), a hormone that inhibits GH release, to the same cell cultures showed the existence of two subpopulations: one was responsive to both hGRF and SRIF (53%, n = 62), another was only responsive to SRIF (47%, n = 62). Human GRF did not affect prolactin release and did not modify the electrical properties of cells responding to dopamine and therefore considered as lactotrophs. These results suggest that (1) hGRF leads to an increase in growth hormone release and a modification of membrane electrical properties by means of an extracellular Ca2+-dependent pathway, and (2) according to their responses to SRIF and hGRF, there are at least two subpopulations of somatotrophs. PMID- 2575713 TI - [The concept of suppressor genes in the molecular biology of central nervous system tumors]. AB - Recently, major advances have resulted from the application of molecular biology to the understanding of central nervous system neoplasia. Schematically, two fundamental mechanisms of tumorigenesis have been described: the activation of oncogenes, and the inactivation of so called recessive "tumor suppressor" genes or "anti-oncogenes". The present report deals with the second mechanism. We discuss its basic concept and techniques, and illustrate it by specifc examples of recent work on brain tumors. The goal of this review is to familiarize Neurosurgeons with the terminology and techniques in this field. Molecular genetics suggest that cancer is a molecular disease which involves regulator genes. These play a major role in growth control, differentiation, and physiology. In the near future molecular biology may identify the structure of proteins coded by suppressor genes, possibly allowing a better tumor classification creating a new "genetic therapy", based on a better comprehension of the role of these genes in dividing and differentiating cells. PMID- 2575715 TI - Dual effects of lephetamine on spontaneous and evoked neuronal firing in the somatosensory cortex of the rat. AB - Lephetamine is a central analgesic, recently shown to be abused by drug addicts and to induce dependence in humans. The drug was applied microiontophoretically on single neurones of the somatosensory cortex of the rat in vivo. Its activity on the spontaneous and evoked firing rate was recorded. Morphine and naloxone were employed to verify the hypothesis that a mu-opiate mechanism of action could be involved. The most frequent response evoked by lephetamine was a dose dependent excitation non-reversible by naloxone. On the other hand, units inhibited or apparently unaffected by the drug, showed a selective anti-glutamate (and partly anti-acetylcholine) effect, which was reversed by either systemically or iontophoretically-administered naloxone. Long-lasting (8-12 min) applications of lephetamine caused a progressive desensitization of cortical neurones to the inhibitory and anti-glutamate effect. The inhibitory activity of lephetamine and morphine was additive and an increased neuronal excitability was shown by a post inhibitory rebound of glutamate-induced neuronal activity. The action exerted by lephetamine on glutamate-induced excitations and on postsynaptic excitability, its reversibility by naloxone and the occurrence of acute tolerance allow the conclusion that only the inhibitory effect of lephetamine is mediated by an opioid mechanism. The lephetamine-induced excitations, not reversed by naloxone, are difficult to interpret as opioid-mediated. PMID- 2575716 TI - Pyroglutamyl peptidase II inhibition specifically increases recovery of TRH released from rat brain slices. AB - Pyroglutamyl peptidase II (EC 3.4.19-) is a highly specific membrane-bound thyrotropin releasing hormone (TRH) degrading enzyme. To study the functional significance of pyroglutamyl peptidase II in TRH degradation, we synthesized the reversible inhibitor N-1-carboxy-2-phenylethyl (Nimbenzyl)-histidyl-beta naphthylamide (CPHNA). CPHNA inhibited the enzyme with a Ki of 8 microM, but had no effect no TRH receptors or no prolyl endopeptidase (EC 3.4.21.26). It weakly inhibited cytosolic pyroglutamyl peptidase I (EC 3.4.19.3). CPHNA at a concentration of 10(-4) M increased both the basal and potassium stimulated recovery of TRH released from hypothalamic slices by approximately two-fold. An even higher recovery was observed in slices from brain regions with relatively high levels of pyroglutamyl peptidase II. CPHNA had no effect on the basal recovery of gamma-aminobutyric acid or Met-enkephalin released from brain slices but decreased the potassium stimulated recovery of both Metenkephalin and gamma aminobutyric acid. These data further support the involvement of pyroglutamyl peptidase II in the extracellular inactivation of brain TRH. PMID- 2575718 TI - Neuroleptic-induced extrapyramidal symptoms and serum calcium levels. Results of a pilot study. AB - In a prospective study, the association between neuroleptic-induced extrapyramidal symptoms (EPS) and serum calcium levels with special regard to ionized calcium was investigated. The sample included 24 newly admitted psychotic patients who received neuroleptic treatment. The 11 patients in whom EPS developed had significant lower ionized calcium levels and a significant lower ionized calcium/total calcium ratio in the predrug period than the 13 patients without EPS. The difference in predrug total calcium between the same two groups did not reach significance. There was no decrease of calcium levels at the time of onset of EPS. pH values showed a significant negative correlation to ionized calcium levels. Protein levels were within the normal limits during neuroleptic treatment. PMID- 2575717 TI - Somatostatin, neuropeptide Y, GABA and cholinergic enzymes in brain of pentylenetetrazol-kindled rats. AB - We studied the effect of pentylenetetrazol (PTZ)-induced kindling (35 mg/kg, i.p., daily) on somatostatin-like immunoreactivity (SOM) with special attention to the duration of changes (rats were sacrificed either 10 days or 4 months after the development of kindling) and to transmitters or modulators related to somatostatin (neuropeptide Y (NPY), GABA, choline acetyltransferase (ChAT), acetylcholinesterase (AchE]. In rats sacrificed 10 days after the last kindled seizure, SOM was elevated in frontal cortex and striatum (p less than 0.01); NPY was elevated in frontal cortex, striatum and hippocampus (p less than 0.05) of kindled or prekindled rats (i.e., rats which were treated daily with PTZ but did not express three consecutive generalized seizures). ChAT activity was slightly decreased (p less than 0.05) in cortex. GABA levels and AchE activity were unchanged in kindled cortex. In rats sacrificed 4 months after the development of kindling none of the parameters analyzed differed from controls. The present study suggests that the cortical and striatal neurons containing SOM/NPY are affected by PTZ-kindling. The cortical cholinergic system is affected to a much smaller extent. The neuropeptide changes are not persistent, as is the lowered seizure threshold, so they are probably not involved in the maintainance of the latter. PMID- 2575719 TI - Comparison of sensorimotor and cognitive performance of acute schizophrenic inpatients treated with remoxipride or haloperidol. AB - 29 acute schizophrenic patients according to DSM III and ICD-9 underwent examination of performance regarding cognitive and sensorimotor tasks at the beginning and the end of a 28-day neuroleptic treatment with remoxipride or haloperidol in a double-blind design. Psychopathological symptoms were assessed by Brief Psychiatric Rating Scale and Clinical Global Impression, extrapyramidal side effects (ESE) were rated by Simpson-Angus scale. A significant treatment effect for acoustic reaction time tasks, naming of colored stripes and interference could be demonstrated, whereas tapping revealed a significant effect of duration of treatment. Interaction effects regarding time of faults in line tracing, visual sensorimotor reaction time task and interference factor (Stroop test) could be observed. ESE and impairment of performance occurred simultaneously and ESE vanished with clinical improvement. Performance deficits were more pronounced in patients assigned to remoxipride treatment. Possible differential effects on performance under neuroleptic drug treatment will be discussed. PMID- 2575720 TI - Clinical management of dentoalveolar trauma: a discussion of current philosophy and methodology and a review of a case. PMID- 2575721 TI - [Muscular rigidity caused by alfentanil: prevention]. AB - We studied three groups of 30 patients each, undergoing minor orthopaedic surgery, anaesthetized with alfentanil (30 micrograms/kg bolus followed by an infusion of 0.3 micrograms/kg/min), thiopental 3 mg/kg and 70% N2O via facial mask. Patients in group I were treated, three minutes before induction, with vecuronium 0.02 mg/kg i.v., while those in group II were premedicated with diazepam 0.15 mg/kg i.m. 30-45 minutes before induction. Group III served as control. Muscular rigidity was evaluated clinically with a subjective score based on a scale of 0 (no rigidity) to 3 (severe rigidity). Diazepam did not give significant protection from muscular rigidity. Vecuronium administration did not significantly reduced the number of patients who became rigid, but significantly decreased the incidence of severe rigidity (p less than 0.005), the mean rigidity score (p less than 0.05) and the incidence of rigidity at the induction of anaesthesia (p less than 0.0005). We also observed a progressively increasing incidence of rigidity with increasing age (not significantly) and body weight (p less than 0.05 total rigidity, p less than 0.01 severe rigidity). PMID- 2575722 TI - Localization of tyrosine hydroxylase and phenylethanolamine N-methyltransferase immunoreactive cells in the medulla of the dog. AB - The tyrosine hydroxylase (TH)- and phenylethanolamine N-methyltransferase (PNMT) immunoreactive cells of the medulla are closely associated with cardiovascular control in both the cat and rat. Although it is often the species of choice for cardiovascular studies, no previous study had characterized these cell groups in the dog. The TH- and PNMT-immunoreactive cells of the dog were distributed much as they are in both cat and rat but with some species variations, which may be indicative of their functional role. PMID- 2575724 TI - Stimulation of the septal complex increases local cerebral blood flow in the hippocampus in anesthetized rats. AB - The effects of focal stimulation, either electrically or chemically, of the septal complex (i.e. the medial septal nucleus and the nucleus of the diagonal band) on the local hippocampal cerebral blood flow (Hpc CBF) measured by laser Doppler flowmetry were examined in anesthetized rats. Electrical stimulation of the septal complex produced a current-dependent increase in Hpc CBF that was accompanied by an increase in extracellular acetylcholine (ACh) release in the hippocampus. Microinjection of L-glutamate (50-100 nmol) into the septal complex also produced an increase in Hpc CBF. The L-glutamate-induced vasodilative response of Hpc CBF was markedly attenuated after administration of nicotinic cholinergic blocking agent, mecamylamine (2 mg/kg, i.v.). It was suggested that the cholinergic septohippocampal nerve fibers act as an intracerebral vasodilative neural system by releasing ACh from the nerve terminals in the hippocampus and by activating the nicotinic cholinergic receptor. PMID- 2575723 TI - Involvement of non-NMDA receptors in picrotoxin-induced epileptiform activity in the hippocampus. AB - The ability of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) to suppress picrotoxin-induced epileptiform burst activity was examined. Intracellular recordings were obtained from hippocampal CA1 and CA3 pyramidal neurons maintained in vitro. Bath application of CNQX (5 microM) significantly reduced or abolished evoked paroxysmal depolarizing shifts (PDSs) in all CA1 and CA3 neurons tested. In cells where a CNQX-insensitive component in the PDS was manifest, this remaining activity was abolished by the N-methyl-D aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (20 microM), suggesting the existence of a NMDA-mediated synaptic potential. Our results indicate that non-NMDA receptor antagonists are capable of markedly reducing picrotoxin-induced epileptiform activity and that these receptors play an important role in generation of PDSs. PMID- 2575725 TI - Excitatory amino acid receptors in the parallel fibre pathway in rat cerebellar slices. AB - The grease-gap technique was used on young rat cerebellar slices to study the synaptic pharmacology of the parallel fibre pathway. Electrical stimulation of the parallel fibres produced a characteristic response in Purkinje cells: a sharp negative (N) potential, representing the population action potential and underlying parallel fibre EPSP, followed by a slow positive (P) wave, the population inhibitory postsynaptic potential (IPSP). In the presence of 1.2 mM Mg2+, D-2-amino-5-phosphonovalerate (APV, 30 microM) had no effect but both potentials could be inhibited by 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX, 10 microM). Removal of Mg2+ had no effect on the N-potential but enhanced the P wave in an APV-sensitive fashion, particularly when CNQX was present. The results provide further evidence that glutamate is the parallel fibre transmitter and suggest that its acts only on non-NMDA (non-N-methyl-D-aspartate) receptors at synapses with Purkinje cells but on both NMDA and non-NMDA receptors at synapses with inhibitory interneurones. At the latter synapses, the NMDA system is likely to be brought into operation in an activity-dependent manner. PMID- 2575726 TI - CGP 31358 binds to a site on the NMDA receptor that is coupled to both the transmitter recognition site and the channel domain. AB - CGP 31358, a novel triazole, inhibited the binding of L-[3H]glutamate and [3H]MK 801 to the N-methyl-D-aspartate (NMDA) receptor complex in rat brain synaptic membrane fractions, and showed anticonvulsant activity in mice. It had no effect on the strychnine-insensitive binding of [3H]glycine. Saturation and Hill analyses indicated that CGP 31358 binds to a site on the NMDA receptor which is separate from, but coupled to, both the transmitter recognition site and the channel domain. Available data indicate that this site is distinct from those with which tricyclic antidepressants and ifenprodil interact. CGP 31358 is a new chemical entity with a novel mechanism of action at the NMDA receptor, and as such may form a tool for understanding the molecular pharmacology of this receptor-channel complex. PMID- 2575728 TI - BOAA selectively enhances L-glutamate release from guinea pig hippocampal mossy fiber synaptosomes. AB - The neurotoxic amino acids beta-N-oxalylamino-L-alanine (BOAA) and beta-N methylamino-L-alanine (BMAA) were evaluated for possible effects on spontaneous and stimulus-evoked release of L-glutamate (L-Glu) and dynorphin A(1-8)-like immunoreactivity (LI) from guinea pig hippocampal mossy fiber synaptosomes. BOAA (200 microM), but not BMAA (1 mM), was found to significantly increase both basal cytosolic and KCl-stimulated vesicular release of L-Glu. Neither BOAA nor BMAA had any effect on dynorphin A(1-8)-LI release from these synaptosomes. This is the first report describing a presynaptic facilitatory action of BOAA upon L-Glu release; an effect which may contribute to the neurotoxic properties of this proposed environmental toxin. PMID- 2575727 TI - Effect of several vasoactive agents on guanylate cyclase activity in isolated rat brain microvessels. AB - We tested the ability of the following putative vasoactive agents to stimulate guanylate cyclase activity in isolated rat cerebral microvessels: angiotensin II, arginine vasopressin, atrial natriuretic peptide, bradykinin, carbachol and thrombin; at concentrations ranging between 10(-3) and 10(-9) M. The ability of cerebral microvessels to increase their cyclic GMP generation was ascertained in the presence of sodium nitroprusside. Of all the agents tested, only atrial natriuretic peptide stimulated cyclic GMP generation in isolated rat cerebral microvessels. Such stimulation was dose-dependent, reaching its maximum at 1 microM concentration. These results are consistent with the finding of atrial natriuretic peptide receptors in brain microvessels, and suggest that this peptide has an important role in modulating the function of brain capillaries, which constitute the blood-brain barrier. If receptors for the other vasoactive agents exist in brain microvessels, their action does not seem to be mediated by cyclic GMP as a second messenger. PMID- 2575729 TI - Dynorphin-containing pilomotor neurons in the superior cervical ganglion of guinea pigs. AB - Retrograde axonal tracing and double-labelling immunofluorescence have been combined to determine the neuropeptide content of identified pilomotor neurons in the superior cervical ganglion of guinea pigs. These neurons lacked immunoreactivity to neuropeptide Y (NPY) but they generally contained low levels of immunoreactivity to prodynorphin-derived peptides, including dynorphin A(1-8), dynorphin A(1-17), and alpha-neo-endorphin. Thus pilomotor neurons are neurochemically distinct from superior cervical ganglion cells which contain immunoreactivity to NPY and prodynorphin-derived peptides and which innervate the iris and most of the vasculature in the head of guinea pigs. They are also distinct from sympathetic secretomotor neurons which lack both NPY and prodynorphin-derived peptides. PMID- 2575730 TI - Cerebellar granule cell survival and maturation induced by K+ and NMDA correlate with c-fos proto-oncogene expression. AB - Persistent depolarization with a high K+ concentration (30 mM) or sustained activation of N-methyl-D-aspartate (NMDA) receptors (12.5 mM K+ plus 100 microM NMDA) enhance both survival and maturation of mouse cerebellar granule neurons in vitro taking as criteria the amount of protein and DNA and the release of endogenous glutamate respectively. K+ and NMDA neurotrophic effects are associated with c-fos protein expression in the nucleus of these cells suggesting that c-fos protein could play a role in the survival and/or maturation of granule neurons. PMID- 2575731 TI - Quisqualate and N-methyl-D-aspartate synergistically excite cerebellar Purkinje cells as a long-term effect. AB - Interactions between the excitatory amino acids (EAAs) quisqualate (QUIS) and N methyl-D-aspartate (NMDA) were investigated in order to explore mechanisms which may help to explain long-term changes in synaptic efficacy induced by these agents. In 93% of the cerebellar Purkinje (Pnj) cells recorded extracellularly which responded to iontophoretic application of QUIS with increases in discharge of up to 100% above spontaneous levels. NMDA administration sensitized the neuron to further QUIS stimulation by 40-200% over control levels of response. NMDA enhanced QUIS responses reached maximal levels after termination of NMDA application and persisted for up to 2 h post-NMDA. The NMDA receptor blocker 2 amino-5-phosphonovalerate (APV) prevented the observed effect only when administered before but not after NMDA application, suggesting that a long lasting post-receptor mechanism may be involved in the observed synergistic interaction of QUIS and NMDA. PMID- 2575733 TI - [Transmitters in early embryogenesis (new data)]. AB - New author's findings and published experimental data on participation of transmitters in first cleavage divisions are discussed. The data on qualitative peculiarities of intracellular transmitter receptors (or their functional equivalents), functional coupling of transmitters with secondary messengers and role of cortical cytoskeleton in realization of transmitter functions are confirmed. PMID- 2575732 TI - Co-localization of adrenergic receptors and vitamin-D-dependent calcium-binding protein (calbindin) in the dopaminergic amacrine cells of the rat retina. AB - Using antisera against tyrosine hydroxylase (TH) and purified beta 2-adrenergic receptors (beta 2-AdR), we found that TH- and AdR-like immunoreactivities coexisted in large amacrine cells. These findings indicated an association between dopamine-containing amacrine cells and adrenergic amacrine cells. The present study also showed that amacrine cells with TH-like immunoreactivity have vitamin-D-dependent calcium-binding protein (calbindin, 27,000 kDa)-like immunoreactivity as well, suggesting that calbindin plays an important postsynaptic role in dopaminergic amacrine cells. PMID- 2575735 TI - [In vitro stimulation of alkaline phosphatase and gamma- glutamyltransferase in the kidney of hypophysectomized rat by the mixture of 1,25 and 24,25 dihydroxycholecalciferols]. AB - The present study was undertaken to investigate the in vitro effects of two cholecalciferol metabolites 1,25(OH)2CC and 24,25(OH)2CC on the renal cortex alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) and acid phosphatase (ACP) activities in hypophysectomized rats. We found that both 1,25-CC and 24,25 CC stimulated ALP and GGT. An additive effect was obtained on ALP and GGT after incubation with one with the other metabolites. When 1,25-CC was used alone, it increased ACP; in presence of 24,25-CC, this stimulating effect disappeared. In the rat, together 1,25-CC and 24,25-CC correct in vitro ALP and GGT activities decreased by hypophysectomy. Physiological signification of these effects remains again unknown. PMID- 2575734 TI - [Free flow electrophoresis. Application to the separation of 2 populations of proximal tubule cells from the rabbit kidney]. AB - Two cell populations from the proximal tubule of the rabbit kidney were separated by free flow electrophoresis from a pure suspension of proximal tubular cells obtained by a combination of a Ca-binding agent, gentle mechanical forces and differential sifting. Before the electrophoretic separation, distal and proximal enzyme activities were measured on the cortical homogenates, on the proximal tubule suspensions and on the isolated cell samples in order to assess the purity of the cell preparation. The isolated cells were very poor in distal tubule marker activities and were enriched in proximal tubule marker enzymes. Cell oxygen consumption was measured before and after the electrophoretic run were similar and reflected high cell metabolic capacity. The cells in the slow-moving electrophoresis fractions had a high gamma-glutamyl transpeptidase activity and the fast moving cells showed a high glucose-6-phosphatase activity. These results point out a separation of viable cells from straight and convoluted portion of the proximal tubule from the rabbit kidney. These two cell populations can be suitable for further use in biochemical and physiological studies. PMID- 2575736 TI - Antihistamines in allergic rhinitis. PMID- 2575738 TI - Routine HLA-DP typing by RFLP analysis. AB - HLA-DP typing using the Primed Lymphocyte Test (PLT) is a long and cumbersome technique requiring DP sensitized clones and bulk reagents. We describe here the use of restriction fragment length polymorphism (RFLP) analysis. This method is quicker and was found to be reliable after comparative analysis of the results between PLT and RFLP in 15 local families and 72 core cell lines from the Tenth International Histocompatibility Workshop. PMID- 2575737 TI - Carrier detection in hemophilia using pedigree analysis coagulation tests and DNA probes. AB - Hemophilia A and B are hereditary X-linked recessive bleeding disorders due to an anomaly or absence of the gene coding for coagulation factors VIII or IX. Until recently, carrier detection was performed on standard pedigree analysis and clotting factor assays. Due to lyonisation, the results obtained by these methods were only probabilistic. Recombinant DNA procedures have now been applied to the identification of molecular defects and carrier detection in inherited diseases. Because of the great heterogeneity of the molecular defects in hemophilia, the diagnosis of carrier status has to be made by the study of restriction fragment length polymorphisms (RFLP) genetically linked to factor VIII or factor IX genes. In a large number of cases, gene probing provides certain diagnosis. We studied some 300 individuals belonging to 70 families with hemophilia A or B. We used two probes to explore hemophilia A: an intragenic probe, p114.12, which detects an RFLP with the enzyme BclI and the extragenic polymorphic probe, St 14, which reveals an RFLP with the enzyme TaqI. For hemophilia B a genomic probe comprising exons b, c, d was used to detect an RFLP linked to a TaqI site. Despite the risk of recombination due to its extragenic location, the St 14 probe proved to be very useful because of the high informativity obtained in the families with hemophilia A. In contrast, the low informativity of the factor IX probe necessitates a search for other RFLPs in or near the factor IX gene. A comparison of the different methods used for carrier detection showed the possibility of misdiagnosis when using only pedigree analysis and biologic data and the improved certainty of diagnosis by gene probing. PMID- 2575739 TI - Management of allergic rhinitis: focus on intranasal agents. AB - The clinical manifestations of allergic rhinitis are the result of an immune mediated process after exposure of a sensitized individual to airborne allergens. The primary symptomatology includes nasal congestion, rhinorrhea, nasal and conjunctival pruritus, and sneezing. Principles of management include allergen avoidance, palliative therapy, immunotherapy, and pharmacotherapy. Oral decongestants stimulate alpha-adrenergic receptors in the nasal cavity, resulting in vasoconstriction and decreased edema. Oral antihistamines block histamine1 (H1) receptors, and may relieve rhinorrhea, sneezing, and nasal and conjunctival pruritus. Topical decongestants have a local effect on adrenergic receptors in the nasal mucosa, resulting in rapid, marked vasoconstriction. Intranasal corticosteroids inhibit mediator release from mast cells and basophils, and reduce edema of the nasal mucosa. Dexamethasone sodium phosphate, beclomethasone dipropionate, and flunisolide are currently available for intranasal administration. Cromolyn sodium inhibits allergen-induced degranulation and mediator release from sensitized cells, and is useful primarily as a prophylactic agent. Several agents, including the corticosteroids budesonide and flucortin butylester, the mast cell-stabilizing agent nedocromil sodium, the anticholinergic agent ipratropium bromide, and the H1 receptor antagonist levocabastine are being investigated for intranasal use in the management of allergic rhinitis. PMID- 2575740 TI - [Hopes raised in connection with erythropoietin treatment of patients with chronic renal failure]. PMID- 2575741 TI - CD 15 antigen in Hodgkin's disease. AB - A retrospective analysis of 117 cases of Hodgkin's disease treated at the Centre G.F. Leclerc between 1976 and 1985 was performed with three objectives: 1): to re evaluate the histologic subtype by the Lukes-Rye classification according to recent data; 2): to demonstrate the frequency of CD 15 antigen by an indirect, three stage immunoperoxidase technique on initial node biopsy histologic sections; 3): to study the prognostic value of this antigen. Histologic reclassification disclosed that 9 cases were in fact non Hodgkin's lymphoma. The remaining 108 cases were classified as lymphocyte predominant (n = 11), nodular sclerosis (n = 77), and mixed cellularity (n = 17), with no cases of either lymphocyte depletion or nodular paragranuloma of Poppema and Lennert identified. In these specimens, fixed in Bouin's solution and embedded in paraffin, CD 15 antigen was detected in the Reed-Sternberg cells and the mononuclear variety of Hodgkin cells in 64 patients (59%). The presence of this antigen was independent of histologic subtype, patient age or sex, clinical stage and the presence of systemic symptoms. Both actuarial disease-free and overall survivals showed that the prognosis of Hodgkin's disease is more favorable in CD 15 positive cases. PMID- 2575743 TI - Recurrent renovascular hypertension in Takayasu's disease. PMID- 2575742 TI - Does a common pathophysiological basis exist in the association of ulcerative colitis and Takayasu's aortitis? Report of a case. AB - A case of a young Japanese woman with long-standing ulcerative colitis complicated by preinfarction angina due to Takayasu's aortitis is presented. Successful emergency aorto-coronary bypass operation was performed. Whether the association of these two diseases can be explained by a common mechanism is discussed. PMID- 2575744 TI - Benzodiazepine dependence. AB - Though safer than their predecessors, the side-effects make the long-term use of benzodiazepines hazardous. Withdrawal can often be achieved, although some individuals will probably remain dependent for the rest of their lives. PMID- 2575745 TI - Autosomal dominant polycystic kidney disease: prenatal diagnosis by DNA analysis and sonography at 14 weeks. AB - A pregnant woman affected with autosomal dominant polycystic kidney disease (ADPKD) had a history of an affected fetus, diagnosed by sonography at 29 weeks of pregnancy. The proband's father was also affected. DNA analysis performed on chorionic villi at 11 weeks during a second pregnancy predicted an affected fetus, and sonographic examination at 14 weeks confirmed the diagnosis. PMID- 2575746 TI - A novel stereospecific synthesis of 14C labeled 1-glutamic acid. AB - A stereospecific synthesis of 4-14C-1-glutamic acid was completed in five steps from sodium 2-14C-acetate. The morpholine derived enamine of ethyl pyruvate was reacted with ethyl 2-14C-bromoacetate to give after hydrolysis diethyl 4-14C-2 oxoglutarate. The 2-oxoglutarate was reacted with hydroxylamine hydrochloride to give diethyl 4-14C-2-hydroxyiminoglutarate which was then reduced with a LiAlH4, (-)-N-methylephedrine and 3,5-dimethylphenol mixture to give 4-14C-1-glutamic acid. The 4-14C-1-glutamic acid was used in investigations into the biosynthesis of gamma-lactones in sherries. PMID- 2575748 TI - On the spatial spread of the grey squirrel in Britain. AB - We present a diffusion-competition model to describe the interaction between the externally introduced grey squirrel and the indigenous red squirrel in Britain. We estimate the model parameters from field data. Solution of the model predicts waves of grey squirrel invasion with speed of invasion typical of that observed in the field. Numerical solution of the model on a two-dimensional domain gives population distributions qualitatively similar to those observed. We suggest that competition alone could account for the observed displacement of the red squirrel by the grey in large regions of Britain. The solutions are qualitatively similar to those for a single species spreading in the absence of competition. The quantitative difference is because competition slows down the speed of advance of the invading species. PMID- 2575747 TI - Effect of ionizing radiation on haemoglobin: the oxy-derivative of haemoglobin Iwate. AB - It is well established that exposure of oxyhaemoglobin to ionizing radiation results in remarkably selective electron addition to the (FeO2) unit, giving a novel species, (FeO2)-, in which the extra electron is largely localized on iron and dioxygen. This work has now been extended to haemoglobin (Hb.) Iwate. The haemoglobin M. Iwate used is a mutant haemoglobin having only Fe(III) alpha chains by oxy beta-chains (alpha 2 Met beta 2 oxy). The haem iron atoms in the alpha-chains are coordinated in the fifth site by a proximal tyrosine in place of histidine. This unit is a high-spin Fe(III) with axial symmetry and prominent electron spin resonance (ESR) features in the g = 6 and g = 2 regions. On exposure to 60Co gamma-rays at 77 K, efficient electron addition occurred at both types of iron centre, giving Fe(II) and (FeO2)- units. The former was monitored by the decrease of the g = 6 feature for Fe(III) and the latter by the growth of g-features at 2.254 (gx), 2.149 (gy) and 1.967 (gz). These values are close to those for the FeO2- centre formed in the beta-chains of normal oxyhaemoglobin. On annealing above 77 K, two changes occurred: first there was a small but clear increase in gx and gy, followed by a marked reduction in gx and gy giving g values close to those for the centre formed directly in the alpha-chains of the normal protein. Finally, this intermediate species gave a centre having gx = 2.310, gy = 2.180 and gz = 1.935. These values are typical of low-spin Fe(III) haemoglobin and are assigned to the protonated complex, Fe(III)O2H. Ultimately at ca. room temperature, this was converted into the high-spin, met-form, with a gain in the g = 6 feature. These results established that the beta-chain centre in Hb. Iwate behave in the same way as isolated beta-chains. They also confirm that electron addition to the oxy-units is facile, even in the presence of Fe(III) units in each tetramer. The results also confirm that electron capture to give (FeO2)- units is not followed by internal electron-transfer to give Fe(II) from the Fe(III) centres in the alpha-chains. PMID- 2575749 TI - Doubly modifiable synapses: a model of short and long term auto-associative memory. AB - Synapses that can be strengthened in temporary and persistent manners by two separate mechanisms are shown to have powerful advantages in neural networks that perform auto-associative recall and recognition. A multiplicative relation between the two weights allows the same set of connections to be used in a closely interactive way for short-term and long-term memory. Algorithms and simulations are described for the storage, consolidation and recall of patterns that have been presented only once to a network. With double modifiability, the short-term performance is dramatically improved, becoming almost independent of the amount of long-term experience. The high quality of short-term recall allows consolidation to take place, with benefits from the selection and optimization of long term engrams to take account of relations between stored patterns. Long-term capacity is greater than short-term capacity, with little or no deficit compared with that obtained with singly modifiable synapses. Long-term recall requires special, simply implemented, procedures for increasing the temporary weights of the synapses being used to initiate recall. A consolidation algorithm is described for improving long-term recall when there is overlap between patterns. Confusional errors are reduced by strengthening the associations between non overlapping elements in the patterns, in a two-stage process that has several of the characteristics of sleep. PMID- 2575750 TI - Changes in cytosolic calcium monitored by inward currents during action potentials in guinea-pig ventricular cells. AB - Action potentials were recorded from single cells isolated from guinea-pig ventricular muscle. Contraction was measured with an optical technique. Tail currents thought to be activated by cytosolic calcium were recorded when action potentials were interrupted by application of a voltage-clamp. A family of tail currents was recorded by interrupting the action potential at various times after the upstroke. The envelope of tail current amplitudes was taken as an index of changes in cytosolic calcium. Consistent with this interpretation, tail currents were negligible following intracellular loading with the calcium chelator BAPTA to suppress calcium transients. The cytosolic calcium transient estimated from the envelope of tails reached a peak approximately 50 ms after the upstroke of the action potential, and fell close to diastolic levels before repolarization was complete; 10 mM caffeine delayed the time to peak contraction, and caused a prolongation of the cytosolic calcium transient estimated from the envelope of tail currents. Caffeine also induced the appearance of a distinct late plateau phase of the action potential. Intracellular BAPTA suppressed the late plateau, contraction and tail currents in cells exposed to caffeine. Exposure to caffeine increased the time constant for decay of tail currents (from approximately 25 to 70 ms). When action potentials were greatly abbreviated by interruption with a voltage-clamp, a progressive decline occurred in the subsequent three contractions and tail currents. There was a progressive reversal of these effects over four responses when the full action potential duration was restored. None of these effects was observed in cells exposed to caffeine. Calcium-activated tail currents appear to be a useful qualitative index of changes in cytosolic calcium. The observations are consistent with the suggestion that cytosolic calcium is reduced during the plateau by a combination of calcium extrusion through Na-Ca exchange and calcium uptake into caffeine-sensitive stores. It also appears that reduction of stores loading during abbreviated action potentials reduces subsequent contraction in cells not exposed to caffeine. PMID- 2575751 TI - Immunocytochemical localization of nicotinic acetylcholine receptors in the terminal abdominal ganglion of the cockroach (Periplaneta americana). AB - A polyclonal, monospecific antiserum raised against a nicotinic acetylcholine receptor protein affinity-purified from insect nervous tissue, was employed to demonstrate the localization of antigenic sites in the neuropile of the terminal (sixth) abdominal ganglion of the cockroach Periplaneta americana. In agreement with previously published autoradiographic mapping of specific [125I]alpha bungarotoxin binding sites, specific areas of the central neuropile of this ganglion were densely stained, but not the cercal afferent axons. No staining was detected corresponding to the dense, peripheral, partly non-specific binding of alpha-bungarotoxin seen in autoradiographs of the same tissue. Certain peripherally located neuronal cell bodies, including the cell body of giant interneuron 2, contained intracellularly located antigenic sites. PMID- 2575752 TI - Inositol 1,4,5-trisphosphate-induced calcium mobilization is localized in Xenopus oocytes. AB - Injection of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) into the animal pole of Xenopus oocytes induced membrane depolarization due to the internal mobilization of calcium, which activates a chloride conductance. Repetitive injections of Ins(1,4,5)P3 results in desensitization probably as a result of depletion of the internal store of calcium. Desensitization was restricted to the region surrounding the site of injection. Injection of Ins(1,4,5)P3 at one position induced desensitization, which failed to spread to a neighbouring region (ca. 200 microns away). Even when sufficient Ins(1,4,5)P3 was injected to induce calcium oscillations, there was still no evidence for the effects of Ins(1,4,5)P3 spreading to neighbouring regions. The fact that periodic calcium transients could also be established by the repetitive injection of small amounts of Ins(1,4,5)P3 suggests that calcium oscillations may also be localized. It is concluded that the Ins(1,4,5)P3-sensitive store of calcium comprises separate local compartments that can be activated independently of each other. PMID- 2575753 TI - Evolution of resistance with sequential application of insecticides in time and space. AB - The effect, on the evolution of resistance, of alternating two unrelated insecticides in space or in time (or both) is studied. Transient polymorphism is shown to occur under certain conditions of mating, selection and migration. In some situations, the transient polymorphism can show a sharp decline before the alleles recover to fixation. Alternating a single insecticide in space, and in space and time, is also considered. Neither alternation in space nor in time shows any advantage with regard to delaying the onset of resistance. The most promising mode is to alternate the presence and absence of a single insecticide in both space and time, especially if it is applied at the larval stage and if some form of biological control is used in the regions where no insecticide is applied. PMID- 2575754 TI - Large deletions encompassing the entire alpha- and beta-like globin gene clusters in humans. PMID- 2575756 TI - DNA haplotypes and the beta s globin gene. PMID- 2575755 TI - The spectrum of beta-thalassaemia in Burma. AB - The molecular defects causing beta-thalassaemia (beta-thal) have been analyzed in 63 unrelated Burmese patients. The patients include 49 with Hb E/beta-thal, 13 with beta-thal major and 1 with Hb S/beta-thal. Using synthetic oligonucleotide probes and aided by the polymerase chain reaction 64/76 (84%) of the alleles have been characterized. To date 6 mutations have been identified. The most common mutation is the splicing defect at IVS-1 nt 1 which accounts for 32% of the alleles. Complete characterization of these alleles should aid the initiation of a prenatal diagnosis programme for beta-thalassaemia in the Burmese population. PMID- 2575757 TI - Effect of dietary restriction on triglyceride levels in the uterus isolated from pregnant rats. Influences of prostaglandins and indomethacin. AB - Triglyceride (TGs) concentrations in uterine strips isolated from 14 or from 21 days-pregnant rats, either normal-fed or following a restricted-diet rats (50% food intake for 14 days), were measured. Determinations were made immediately after killing (0 min time or post-isolation) as well as after a period of incubation in glucose-free medium (60 min time or post-incubation). The post isolation levels of TGs (0 min) in the uterus from normal-fed animals at 14 or at 21 days of pregnancy, were significantly higher in implantation sites than in the interembryonic segments. These values of TGs (0 time) did not change, in comparison to post-incubation concentrations (60 min), either without additions or in the presence of indomethacin (5 X 10(-6) M) or of prostaglandins (PGs) E1, E2 or F2 alpha (10(-7) M). At 0 time, uterine TGs of rats subjected to dietary restriction, increased as pregnancy progressed, more than in normal-fed controls. The post-incubation (60 min) pattern was different depending on the days of pregnancy; i.e. at 14 days, incubation in Krebs-Ringer Bicarbonate-medium (KRB) led to a significant fall unaffected by the addition of propranolol (10(-6) M). However, in the presence of indomethacin, TGs values had a level similar to the initial one (0 time). Furthermore, exogenous PGE1 or PGE2 failed to alter the effect of indomethacin, as PGF2 alpha did.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575758 TI - Effects of (+-)3,4-methylenedioxymethamphetamine (MDMA) on brain dopaminergic activity in rats. AB - Acute treatment with (+-)3,4-methylenedioxymethamphetamine (MDMA) at high doses (10 and 30 mg/kg, IP), but not lower doses increased locomotor activity in male rats. MDMA did not consistently produce any other stereotyped behaviors at any dose. Dopamine (DA) turnover rate as estimated by the ratio of brain tissue levels of 3,4-dihydroxyphenylacetic acid (DOPAC) over DA was decreased in the striatum for up to two hours after acute treatment with 10 mg/kg of MDMA. DA turnover rate was inconsistently decreased in the olfactory tubercle and medial basal hypothalamus, and was unchanged in the medial prefrontal cortex and the substantia nigra/ventral tegmental area. Two hours after a 30 mg/kg injection of MDMA, DA turnover rate was decreased in all brain areas tested. MDMA and d amphetamine partially reversed a haloperidol-induced elevation of striatal DOPAC levels. In contrast, the nonamphetamine stimulant, amfonelic acid, enhanced haloperidol's effect. In chloral hydrate-anesthesized rats, MDMA injected IV partially inhibited spontaneous firing rate of DA neurons in the substantia nigra (34% decrease at 4 mg/kg of MDMA). Seventeen days after subchronic MDMA treatment (10 or 20 mg/kg, IP, twice per day for four days), DA and DOPAC levels were unchanged in all brain areas tested as compared to levels in control rats. It is concluded that acute treatment with high but not low doses of MDMA has a weak amphetamine-like effect on nigrostriatal as well as mesolimbic/mesocortical and tuberoinfundibular DA neurons in rats. Repeated treatment with MDMA does not appear to be toxic to mesotelencephalic or tuberoinfundibular DA neurons. PMID- 2575759 TI - Stimulus effects of N-monoethyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDE) and N-hydroxy-1-(3,4-methylenedioxyphenyl)-2-aminopropane (N-OH MDA) in rats trained to discriminate MDMA from saline. AB - Tests of stimulus generalization were conducted using rats trained to discriminate 1.5 mg/kg of N-monomethyl-1-(3,4-methylenedioxyphenyl)-2 aminopropane HCl (MDMA) from saline in order to determine if two structurally related analogs (MDE and N-OH MDA) would produce similar stimulus effects. The MDMA-stimulus (MDMA, ED50 value = 0.76 mg/kg) generalized both to MDE (ED50 value = 0.73 mg/kg) and N-OH MDA (ED50 value = 0.47 mg/kg). Administration of (+)amphetamine resulted in partial generalization (maximum of 49% MDMA appropriate responding) in the MDMA-trained animals. Taken together with our previous studies showing that MDMA substitutes for the phenylisopropylamine stimulant (+)amphetamine, but that neither MDE nor N-OH MDA substitute for (+)amphetamine or for the phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4 methylphenyl)-2-aminopropane (DOM), the present results [i.e., MDMA-stimulus generalization to MDE, N-OH MDA, but not to (+)amphetamine] suggest that 1) MDMA produces effects other than those that may be considered amphetamine-like, and 2) MDE and N-OH MDA are MDMA-like agents with even less of an amphetamine-like component of action than MDMA itself. PMID- 2575760 TI - Reversal of a mecamylamine-induced cognitive deficit with the D2 agonist, LY 171555. AB - Pharmacological blockade of either nicotinic or muscarinic cholinergic receptors has been found to impair choice accuracy in the radial-arm maze. Simultaneous blockade of both of these receptor types causes an additive impairment. However, despite these common effects, nicotinic and muscarinic receptors have been found to have differential involvement with dopamine receptors. The cognitive impairment caused by the muscarinic antagonist scopolamine is reversed by the D1 antagonist SCH 23390 but is unaffected by the D2 antagonist raclopride. In contrast, the cognitive impairment caused by the nicotinic antagonist mecamylamine is unaffected by SCH 23390 but is potentiated by raclopride. In the current study, the D2 agonist LY 171555 was found to be effective in reversing the radial-arm maze choice accuracy impairment caused by mecamylamine. In contrast, the D1 agonist SKF 38393 was not found to be effective. Thus, we have found selective dopaminergic D1 and D2 treatments which counteract the adverse cognitive effects of either nicotinic or muscarinic blockade. A combination of these treatments may be useful in treating the cognitive effects of generalized cholinergic underactivation. PMID- 2575761 TI - [Application of dipeptidylpeptidase IV in formation of the peptide bond]. AB - According to the increasing importance of enzyme catalysed peptide synthesis the capability of the protease dipeptidyl peptidase IV is shown to form the peptide bond. To our best knowledge, it's the first time that has been used successfully proline as one of the amino acids. The formation of the peptide bond is kinetically controlled. Free amino acids have been used as nucleophiles. The reaction media contain 50 vol.-% glycerol. A first approach to a kinetic treatment is shown. PMID- 2575762 TI - In vitro pharmacologic profile of the novel beta-adrenoceptor antagonist and vasodilator, carvedilol. AB - The pharmacologic profile of the novel beta-adrenoceptor antagonist/vasodilator, carvedilol, has been investigated in vitro. Carvedilol produced competitive antagonism of the beta 1-adrenoceptor mediated positive chronotropic response to isoproterenol in guinea pig atria, and the beta 2-adrenoceptor mediated relaxation to isoproterenol in carbachol (1 mumol/l) precontracted guinea pig trachea, with a dissociation constant (KB) for beta 1-adrenoceptors of 0.8 nmol/l and beta 2-adrenoceptors of 1.3 nmol/l. At slightly higher concentrations, carvedilol produced competitive inhibition of the alpha 1-adrenoceptor mediated contractile response to norepinephrine in rabbit aorta with a KB of 11 nmol/l. Carvedilol had no significant effect on the contractile response to angiotensin II in rabbit aorta at concentrations up to 10 mumol/l, thus demonstrating the lack of nonspecific vasodilator actions in arteries. In canine saphenous vein, carvedilol produced noncompetitive blockade of alpha 2-adrenoceptor mediated vasoconstriction, indicative of some additional activity. In estrogen-primed rat uterus precontracted by depolarization with KCl (70 mmol/l), carvedilol produced concentration-dependent relaxation (IC50 of 7.6 mumol/l), consistent with the notion that carvedilol may be a calcium channel antagonist. Support for this hypothesis was obtained in KCl (70 mmol/l) depolarized rabbit aorta where carvediol (10 mumol/l) produced a 10-fold parallel rightward shift in the concentration-response curve to calcium chloride. These studies demonstrate that carvedilol is a potent beta 1-, beta 2- and alpha 1-adrenoceptor antagonist, and a moderately potent calcium channel antagonist. These multiple activities of carvedilol may contribute to the antihypertensive activity of the compound. PMID- 2575763 TI - Clinical and pharmacokinetic evaluation of zuclopenthixol acetate in Viscoleo. AB - The purpose of the present study was to evaluate zuclopenthixol acetate in Viscoleo, a new preparation to be administered once every 3 days, in the early treatment of acute psychotic episodes and acute deterioration of chronic psychosis. 21 cases were included in the study: patients received 1 to 3 injections. Clinical evaluation was made at 24, 48 and 72 hours after each injection, using the Clinical Global Impressions (CGI) and the Brief Psychiatric Rating Scale (BPRS). Results at end-point indicated a marked or moderate therapeutic effect in the 11 cases of acute psychosis. A statistically significant decrease was observed for the total BPRS score as well as for its subscales. Among 8 cases of exacerbation of chronic psychosis, 4 patients showed a moderate therapeutic effect, and minimal or no effect was found in the other 4 subjects. The total BPRS decreased significantly, but to a lesser extent than for acute psychosis. Two patients suffering from mania showed a moderate therapeutic effect according to CGI. 8 cases of acute psychosis and 5 cases of chronic psychosis did not suffer from any neurological side-effects. Plasma concentration measurements suggest that a dose of 50 mg per 3 days may be sufficient for early treatment of most acutely ill psychotic patients. PMID- 2575764 TI - Pharmacological studies on perazine and its primary metabolites. AB - The study served to answer the question whether metabolites possibly contribute to the clinical actions of the neuroleptic drug perazine. The primary metabolites demethylperazine and perazine sulfoxide were investigated with regard to influences on behavior in mice, to an antiemetic action in dogs, and to a modification of the pressor effect of noradrenaline in rats. In contrast to perazine, none of the metabolites exhibited effects that can be interpreted to indicate neuroleptic or antidepressive properties of the compounds. PMID- 2575765 TI - The efficacy of Cavain in patients suffering from anxiety. AB - The therapeutical efficacy of Cavain should be proved in the treatment of patients suffering from abnormal anxiety, psychosomatic complaints and psychoreactive disorder. Thus two randomized groups of patients (26 each) were treated in double-blind technique with either 2 x 200 mg daily Cavain or placebo for a period of 28 days. Prior to the beginning of the investigations and within 14 days intervals the Hamilton Anxiety Scale (HAMA) and the Adjective Check List (Janke and Debus) were applied. The global therapeutical improvement and compatibility were documented after 14 and 28 days. A significant superiority of Cavain in comparison to placebo could be found. Cavain acted anxiolytically and promotive on the subjective vitality-related performance. Therapeutical conclusions are discussed. PMID- 2575766 TI - A comparative study of suriclone, lorazepam and placebo in anxiety disorder. AB - In a four-week double-blind randomized trial preceded by a one-week single-blind placebo treatment, the efficacy and the side-effects of suriclone (1.50-2.25 mg/d) (n = 24), lorazepam (5.0-7.5 mg/d) (n = 19) and placebo (n = 21) were compared in 64 outpatients with a DSM-III diagnosis of generalized anxiety disorder (n = 56) or panic disorder (n = 8). Efficacy was measured weekly by means of a global clinical impression scale, the Hamilton Anxiety Rating Scale, the Zung Anxiety Self-Assessment Scale and a target symptom scale. Side-effects were evaluated weekly by an adverse events scale, which recorded the spontaneous complaints and the complaints elicited by an extensive somatic inventory questionnaire. The three groups showed a statistically significant and clinically relevant improvement early on in the treatment: this improvement was maintained during the remaining period. Early on in the treatment there was some indication of a better response, but also of more side-effects, in the suriclone and the lorazepam groups. After four weeks of treatment no difference was found between the three groups either in efficacy or in side-effects. The effect size achieved in the placebo group was not inferior to that of benzodiazepines in general. PMID- 2575767 TI - Phylogenetic relations between microbats, megabats and primates (Mammalia: Chiroptera and Primates). AB - We examine the paraphylectic hypothesis of bat origins, both in the light of previous discussions, and in the light of new evidence from our analyses of neurological traits and wing morphology. Megabats share with primates a variety of complex details in the organization of neural pathways that have not been found in any other mammalian group, particularly not in microbats. The features previously used to link microbats and megabats have been examined and found to be questionable bases for support of a monophyletic origin. In particular, morphological analyses of the musculoskeletal adaptations associated with the flight apparatus are consistent with two separate origins of the mammalian wing. Taken together, these analyses suggest that megabats evolved from an early branch of the primate lineage. This branch was comprised of moderate-sized, phytophagous gliders, of which the other living descendants are the dermopterans. Microbats, in contrast, probably evolved much earlier from small, agile insectivores whose forelimbs had long metacarpals in relation to their phalanges. PMID- 2575768 TI - The pachypleurosaurids (Reptilia: Nothosauria) from the middle triassic of Monte San Giorgio (Switzerland) with the description of a new species. AB - The largest and most diverse collection of Pachypleurosauridae (Nothosauria, Reptilia) comes from Monte San Giorgio, Switzerland. Several hundred complete skeletons were collected from four distinct horizons of bituminous limestones and shales of Anisian-Ladinian boundary to early Ladinian age (Middle Triassic). Serpianosaurus mirigiolensis comes from the oldest strata, the Grenzbitumenzone Beds. The three younger strata, all in the Lower Meride Limestone, yield three species of Neusticosaurus. Neusticosaurus pusillus comes from the Cava Inferiore horizon, Neusticosaurus peyeri, new species, from the Cava Superiore horizon, and Neusticosaurus edwardsii, new combination, from the Alla Cascina horizon. Neusticosaurus pusillus is biostratigraphically important because it is one of the rare species reported from both the Germanic and the Alpine Triassic. Neusticosaurus pusillus and N. peyeri are small and very similar in their anatomy. Neusticosaurus species are easiest separated by their number of presacral vertebrae. Ornamentation of the bone surface is distinctive for all four pachypleurosaurids. Soft parts are rarely preserved, except for one partial squamation. The biological age of Neusticosaurus individuals can be determined by skeletochronology (aging by bone annuli). Small species of Neusticosaurus were sexually mature after three to four years and lived for six to nine years. Taphonomic analysis of the small species indicates attritional mortality and suggests weak bottom currents in the Monte San Giorgio basin during early Ladinian times. Morphometric comparison of all four pachypleurosaurids indicates that the changing vertebral numbers between species are largely due to a change in number of segments. All Monte San Giorgio pachypleurosaurids are sexually dimorphic in forelimb development. Sex x has poorly differentiated and relatively short humeri whereas sex y has well differentiated and relatively long humeri. The sexes are of about the same size and represented in roughly equal numbers. Identification of gender was not possible. Good growth series, especially of Neusticosaurus peyeri, from embryo to large adult permitted qualitative and quantitative study of ontogeny. The skull grows with negative allometry; the humerus grows isometrically or with positive allometry, depending on sex and species; the femur grows isometrically. The adult size range in N. peyeri is considerably larger than in modern reptiles. The Monte San Giorgio pachypleurosaurids are a monophyletic group. The phylogeny of this group is congruent with the stratigraphic distribution of its members. PMID- 2575769 TI - An allometric study of pulmonary morphometric parameters in birds, with mammalian comparisons. AB - Comprehensive pulmonary morphometric data from 42 species of birds representing ten orders were compared with those of other vertebrates, especially mammals, relating the comparisons to the varying biological needs of these avian taxa. The total lung volume was strongly correlated with body mass. The volume density of the exchange tissue was lowest in the charadriiform and anseriform species and highest in the piciform, cuculiform and passeriform species. The surface area of the blood-gas (tissue) barrier, the volume of the pulmonary capillary blood and the total morphometric pulmonary diffusing capacity were all strongly correlated with body mass. The harmonic mean thickness of both the blood-gas (tissue) barrier and the plasma layer were weakly correlated with body mass. The mass specific surface area of the blood-gas (tissue) barrier (surface area per gram body mass) and the surface density of the blood-gas (tissue) barrier (i.e. its surface area per unit volume of exchange tissue) were inversely correlated (though weakly) with body mass. The passeriform species exhibited outstanding pulmonary morphometric adaptations leading to a high specific total diffusing capacity per gram body mass, consistent with the comparatively small size and energetic mode of life which typify passeriform birds. The relatively inactive, ground-dwelling domestic fowl (Gallus gallus) had the lowest pulmonary diffusing capacity per gram body mass. The specific total lung volume is about 27% smaller in birds than in mammals but the specific surface area of the blood-gas (tissue) barrier is about 15% greater in birds. The ratio of the surface area of the tissue barrier to the volume of the exchange tissue was also much greater in the birds (170-305%). The harmonic mean thickness of the tissue barrier was 56-67% less in the birds, but that of the plasma layer was about 66% greater in the birds. The pulmonary capillary blood volume was also greater (22%) in the birds. Except for the thickness of the plasma layer, these morphometric parameters all favour the gas exchange capacity of birds. Consequently, the total specific mean morphometric pulmonary diffusing capacity for oxygen was estimated to be about 22% greater in birds than in mammals of similar body mass. This estimate was obtained by employing oxygen permeation constants for mammalian tissue, plasma and erythrocytes, as avian constants were not then available.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2575770 TI - The phylogenetic regression. PMID- 2575773 TI - Treating ulcers in patients receiving anti-arthritic drugs. PMID- 2575771 TI - Asymmetry of neuroleptic-induced rigidity: development of quantitative methods and clinical correlates. AB - Twenty-six medicated schizophrenic patients and 14 normal controls underwent laboratory assessment for the presence and asymmetry of neuroleptic-induced rigidity to evaluate the sensitivity, reliability, and validity of a quantitative procedure. Measures of muscle stiffness were made in the upper extremities. Results indicated that 65% of the patients exhibited pathological rigidity. Moreover, 76% of these patients exhibited asymmetric rigidity, while the remaining 24% exhibited bilateral symptoms. Newly treated patients exhibited a greater laterality of rigidity toward the right side compared with patients who were on stable treatment regimens for at least 3 months. Since parkinsonism reflects dopamine receptor blockade by neuroleptic medication, probably in the striatum, we suggest that the lowered susceptibility of the right striatum to drug-induced parkinsonism supports the hypothesis that striatal dopaminergic activity may be asymmetric and more marked in the right striatum among recently treated patients. PMID- 2575772 TI - The dynamics of the organism: implications of recent biological thought for psychosomatic theory and research. PMID- 2575775 TI - A glutamate mechanism in the intermediolateral nucleus mediates sympathoexcitatory responses to stimulation of the rostral ventrolateral medulla. PMID- 2575774 TI - [Morphofunctional characteristics of the cells of the APUD system of the adrenal glands and the duodenum in the cerebral form of acute radiation sickness]. AB - Changes of a phase nature develop in the APVD system cells of rats, dogs, and monkeys exposed to electron radiation of doses inducing a cerebral form of radiation sickness. These changes in the morphofunctional status of APVD system cells may be considered as a syndrome displaying acute radiation apudopathies. PMID- 2575776 TI - Chemical neuroanatomy of the parapyramidal region of the ventral medulla in the rat. PMID- 2575777 TI - Nucleotide sequence and expression of the glutamine synthetase structural gene, glnA, of the archaebacterium Methanococcus voltae. AB - The sequence of a 2,746-bp DNA fragment of Methanococcus voltae carrying the glnA gene for glutamine synthetase (GS), was established. A 1,338-bp open reading frame (ORF), encoding a 446-amino-acid polypeptide of 50,142 Da, was defined as glnA on the basis of its similarity to other glnA genes and on the ability of a DNA fragment carrying this ORF to complement an Escherichia coli Gln- mutant. No sequence homology was found between sequences flanking the M. volae glnA gene and other eubacterial glnA genes. In M. voltae, the gene was transcribed as a monocistronic unit and GS synthesis was partially repressed at high ammonia concentrations. At the amino acid sequence level, the highest similarity was found with GS of Bacillus subtilis and Clostridium acetobutylicum. PMID- 2575778 TI - Amino acid neurotransmitters in iron-induced epileptic foci of rats. AB - Injection of iron salts into the rodent cortex has been shown to cause chronic or recurrent seizures. Amino acid levels in the cerebral cortex were examined 1, 3, 6, 9, 24, 48 hours and 4 weeks after an injection of ferric chloride solution to the left sensory motor cortex of rats. Aspartate level decreased 9 and 24 hours after the injections with ferric chloride. No significant change was observed in glutamate level, though glutamine level decreased 3 and 48 hours after the injection. GABA level decreased 6 hours after the injection. On the contrary, alanine and glycine levels increased 1 and 24 hours, and 24 hours after the injection, respectively. These results suggest that these amino acid neurotransmitters are involved in the acute seizure mechanism and in the process of chronic focus formation in the iron-induced epilepsy of rats. PMID- 2575779 TI - Replication of certain recently classified viruses in Toxorhynchites amboinensis mosquitoes and in mosquito and mammalian cell lines, with implications for their arthropod-borne status. AB - Thirty-one viruses recently placed in taxa were studied for their replication in Toxorhynchites amboinensis by intrathoracic inoculation. Results were compared to those obtained in vitro in mammal and insect cell cultures. These findings provide presumptive evidence for the association of eighteen of these viruses with arthropod vectors. PMID- 2575780 TI - [Reciprocal actions among anti-asthmatic drugs]. PMID- 2575782 TI - [Hypoxic ventilatory depression]. PMID- 2575781 TI - [The effect of bunazosin vs captopril on hemodynamic and neurohumoral parameters in patients with congestive heart failure]. AB - The hemodynamic parameters (right atrial pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac index, heart rate, blood pressure) and neurohumoral responses (alpha-ANP, plasma renin activity, aldosterone, angiotensin II) of Captopril, oral ACE inhibitor, and Bunazosin, oral alpha 1-blocker, were investigated in 28 patients with congestive heart failure at rest and after exercise. These data were analysed in both acute and chronic phases. 1) Acute effect. Captopril produced significant improvement of neurohumoral factors at rest and also after exercise. Bunazosin reduced alpha ANP, but other neurohumoral factors did not change. Bunazosin produced significant hemodynamic improvement both at rest and after exercise. 2) Chronic effect. Captopril produced significant hemodynamic improvement both at rest and after exercise. Improvement of neurohumoral factors in acute phase was also preserved at chronic phase. On Bunazosin, improvement of hemodynamics at acute phase was also preserved at chronic phase without deterioration of neurohumoral factors. PMID- 2575783 TI - The multidrug resistance gene in renal cell carcinoma. PMID- 2575784 TI - Genetics of renal cell carcinoma. PMID- 2575785 TI - [Changes in the symptoms of fatigue among junior high school students as a result of the reforms of the educational programs]. AB - The purpose of this study was determination of changes in the prevalence of subjective feeling of tiredness among students in the first classes of colleges before and after introduction of changes in education programmes. In view of this in 1986 and 1987 an inquiry interview was carried out of 584 students in 5 province capitals. According to the results of this inquiry the students were divided into 3 groups: without symptoms of tiredness, with slight symptoms and with evident tiredness. The analysis of the data showed that evident symptoms of tiredness were present in about half the students, and their frequency was significantly greater among girls. The introduction of changes in the education programmes in the first class of colleges led to a greater prevalence of tiredness symptoms, especially among girls. PMID- 2575786 TI - Cardiac effects of secretin; an approach to its mechanisms of action as shown by beta-adrenergic blockade and measurement of left ventricular dimensions in dogs. AB - In previous studies, the peptide secretin has demonstrated the ability to increase cardiac output and peripheral organ flow. In this investigation the mechanisms of the myocardial effects of secretin were studied. The secretin effects on cardiac output, stroke volume and systemic resistance were unaltered after propranolol, whereas the effect on LVdP/dt was reduced and the heart rate effect negligible. Systemic pressure, myocardial blood flow and myocardial oxygen consumption were unchanged by secretin infusion both before and after beta receptor blockade. Secretin caused reduction of all three end-systolic left ventricular diameters. Thus, an inotropic effect by secretin was confirmed. Beta receptor blockade reduced the inotropic effect and almost abolished the chronotropic effect, whereas the vasodilating effect was unaltered. The main haemodynamic effect of secretin was caused by activation of receptors other than the beta-adrenergic receptors. PMID- 2575787 TI - Plasma glutamate--a prognostic marker of cancer and of other immunodeficiency syndromes? AB - Elevated plasma levels of glutamate (GLU) have been reported to occur in patients with malignancies and other immunodeficiency syndromes (IDS). To evaluate, whether GLU is useful as prognostic indicator, the plasma concentrations were determined in patients with colorectal carcinoma (CRC), with breast cancer (BRC), and with HIV-infection (HIV). The results were correlated with the disease stages, and compared with data obtained from patients with benign diseases of the same organ, as well as from sex-matched healthy volunteers. GLU concentrations (volunteers: 27.4 +/- 17.6 mumol/l) were elevated in all BRC patients (range of mean values: 53.5-83.2 mumol/l), in CRC patients with T2-T4-tumours (means: 46.8 85.9), and in HIV+ patients of stage WR 5, 6 (means: 53.9-69.7 mumol/l). All CRC- and BRC-patients with metastases showed highly significant elevations of GLU concentrations (p less than 0.001), but there were no direct correlations between disease stages and GLU levels. Pre-operative patients with benign diseases (diverticulitis, adenoma = GID; and mastopathy = MTP) showed increased GLU levels, which were comparable to those of the tumour patients. The glutamine/GLU ratios (volunteers: 19.3 +/- 15.0) were decreased only in HIV-WR 6 (7.6 +/- 2.1), and BRC-stage 4 (8.0 +/- 1.7). From these results we deduce that the plasma GLU concentrations do not allow a discrimination either between patients with malignancies and without, and between persons of different disease stages. PMID- 2575788 TI - Oxmetidine in the short term treatment of active duodenal ulcer. A review and commentary. AB - Oxmetidine is an H2-antagonist like cimetidine containing an imidazole ring in its molecule, but differing from cimetidine in that it contains in the side-chain a substituted isocytosine moiety in place of the cyanoguanidine group. Nine controlled clinical trials are critically analysed in detail. The overall results show that the antiulcer activity of oxmetidine is not significantly different from that of cimetidine with mean healing rates by week 4 of 74.9% and 75.3%, respectively. Healing rates proved to be lower in smokers than in non-smokers in all trials but one. Satisfactory response as regards symptoms was obtained both with oxmetidine and cimetidine. A certain degree of variability with regard to the untoward effects was found, but in all cases failed to prove significant from the clinical point of view. However, a better definition of oxmetidine safety requires a study on a large number of patients and for a longer period. PMID- 2575790 TI - Action of the new H2-receptor antagonist oxmetidine on the duodenum of different species. AB - The new H2-receptor antagonist, oxmetidine was studied for its effects on the motility of the duodenum of different species. Oxmetidine did not modify basal motility of the rat and guinea pig duodenum but it reduced or abolished the contractions elicited by different spasmogenic compounds (acetylcholine, BaCl2, KCl, eledoisin). In the rabbit duodenum, oxmetidine reduced in a dose-dependent fashion the basal motility. The effect of this compound appears to be indirect on the smooth muscle and not mediated through specific receptors. Experiments performed in Ca++-free and K+-depolarizing solution suggest that oxmetidine acts through interference with the transport and/or utilization of intracellular Ca++ions. PMID- 2575789 TI - Campylobacter pylori and gastroduodenal ulcer disease. A prospective study in a Swedish population. AB - In a consecutive prospective series of 208 Swedish primary peptic ulcer patients, 146 gastric, 55 duodenal and 7 in both sites, gastroduodenitis was found in 97.6% of the cases. The mucosal inflammation was associated with CP in 87% and 91% of the gastric and duodenal ulcer cases respectively. No significant correlation was found between CP colonisation and the type or severity of mucosal inflammation. Gastric metaplasia was present in only 8% of 48 bulbar ulcer cases. Ulcer healing and eradication of CP was achieved in 52% of patients treated with bismuth subnitrate in combination with erythromycin or according to the triple approach. PMID- 2575791 TI - Managing recurrent oesophagitis. PMID- 2575792 TI - Drug therapy of reflux oesophagitis: an update. AB - The various therapeutic approaches for reflux oesophagitis are to enhance oesophageal clearance, to coat damaged tissue, to increase the competence of the reflux barrier, to reduce the volume and pH of gastric contents, and to improve gastric emptying and pyloric sphincter competence. Unfortunately, drug therapy of reflux oesophagitis is not yet ideal. Of the prokinetic agents, cisapride is the only drug with proven benefit. Single-agent therapy with the H2-receptor antagonists or sucralfate results in similar degrees of symptom relief and healing. Rapid symptom relief and healing are achieved by omeprazole; however, the significance of sustained achlorhydria remains to be established. Dinnertime dosing of cimetidine appears to be a rational method of suppressing late-evening gastric acidity. Patients with severe or recalcitrant disease should not be treated with conventional therapy alone; the results of controlled studies of combination therapy with the H2-receptor antagonists and sucralfate or cisapride will be viewed with interest. PMID- 2575794 TI - Depot neuroleptics. PMID- 2575793 TI - Prognostic value of immunologic abnormalities and HIV antigenemia in asymptomatic HIV-infected individuals: proposal of immunologic staging. AB - The prognostic value of various immunologic tests was investigated in 150 HIV seropositive homosexual men, who were initially without HIV-related symptoms or AIDS and who were followed for a median of 12 months (range 3-28 months). The laboratory investigations included HIV antigen in serum, total lymphocyte count, T-helper (CD4) and T-cytotoxic/suppressor (CD8) counts, and lymphocyte transformation responses to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM), and to antigenic extracts from Candida albicans and cytomegalovirus. 24 individuals developed HIV-related symptoms or AIDS (11 cases). All parameters except the CD8 count were of prognostic value, but a multivariate analysis of symptom-free survival showed that HIV antigenemia, a CD4 count less than 0.5 x 10(9)/l, and relative response to PWM below 25% of controls contained all the prognostic information. Individuals abnormal at entry for these 3 variables had a theoretical 36 times as high hazard of developing symptoms within the observation period as had individuals with normal parameters. There was no significant covariation between HIV antigenemia on the one hand and CD4 count and response to PWM on the other. Although, the latter 2 variables covaried, each of them provided independent information, and both were used to classify the degree of the immunodeficiency in 3 stages: Im-0 with normal values, Im-1 with one, and Im-2 with both tests abnormal. Individuals in stage Im-2 had a 10 times increased risk of developing symptoms. The immunologic staging correlated significantly with the clinical grouping (CDC criteria). This staging improved in only 1, but deteriorated in half of 36 individuals observed for at least 18 months. Thus, the staging is likely to prove useful when attempts to arrest the immunodeficiency of HIV-infected individuals has to be monitored. PMID- 2575795 TI - Tardive dyskinesia. PMID- 2575796 TI - A comparative study of pipothiazine palmitate and fluphenazine decanoate in the maintenance of remission of schizophrenia. AB - This paper reports a randomized, controlled, partially-blinded, flexible dose, parallel group, comparative study of the efficacy and tolerance of pipothiazine palmitate and fluphenazine decanoate in patients in remission from Schizophrenia over a 28 week period. The results show that pipothiazine palmitate is at least as efficacious and well-tolerated as fluphenazine decanoate in preventing relapses from maintained Schizophrenia. PMID- 2575797 TI - Tardive dystonia in Chinese. AB - Three Chinese patients with the under-recognized condition of tardive dystonia are described. This is a physically and socially handicapping complication of neuroleptic treatment. A past history of acute dystonia does not appear to predict the future development of tardive dystonia. The need for judicious indication of neuroleptics is emphasised. PMID- 2575798 TI - [Postoperative agitation]. PMID- 2575799 TI - Spinal subdural empyema complicating cervical discography. PMID- 2575800 TI - Immunoregulatory T cell subsets and T cell activation in rheumatoid arthritis. A need for analysis on the clonal and molecular level. PMID- 2575801 TI - Prevention of lung infections associated with human immunodeficiency virus infection. AB - Current evidence indicates that the length of survival for patients with the acquired immunodeficiency syndrome (AIDS) is increasing, thereby affording a greater opportunity for strategies designed to prevent the infectious diseases that mark the syndrome. Because these infections may occur at different stages of immunosuppression caused by the human immunodeficiency virus (HIV), effective application of preventive measures depends not only on detection of HIV infection but also on the use of staging indicators. The diseases that serve to define AIDS, such as Pneumocystis carinii pneumonia, tend to occur late in the course of HIV infection and often when the T helper lymphocyte (CD4+ cells) count is less than 0.2 x 10(9)/l. Other infections, such as tuberculosis and pyogenic bacterial pneumonia, may develop at any point after HIV infection has occurred. Given this relation between the degree of immunosuppression and the occurrence of particular pulmonary infections, different preventive interventions should be applied at different times. It is now known that the incidence of several of the pulmonary infections that are common in patients with HIV infection can be reduced by prophylactic measures. Pneumocystis pneumonia is decreased in frequency by any one of several prophylactic agents, the best established being pentamidine administered as an inhaled aerosol. The role of isoniazid in the chemoprophylaxis of tuberculosis in patients not infected with HIV is well established. Although there is little evidence of benefit so far from isoniazid in HIV infected patients with a positive tuberculin skin test response, it is logical to assume that there could be some effect. The use of pneumococcal polysaccharide vaccine may also be of some benefit in reducing the frequency of pneumococcal pneumonia in patients with AIDS. In addition to these specific measures, the antiretroviral agent zidovudine decreases both the frequency and the severity of opportunist infections, at least during the first few months of treatment. A comprehensive strategy for prevention of HIV associated lung infection first requires detection of HIV seropositivity, staging the immunosuppression by the CD4+ cell count, and determining whether tuberculous infection is present by a tuberculin skin test. All seropositive individuals should be given pneumococcal vaccine and those with evidence of tuberculosis infection should be treated with isoniazid for one year. Zidovudine should probably be started when CD4+ cell counts are in the range 0.4 0.5 x 10(9)/l and prophylaxis against pneumocystis infection when CD4+ cell counts are in the range 0.2-0.3 x 10(9)/l. PMID- 2575803 TI - Allele-specific occurrence of multiple C4 and Slp mRNAs. AB - The H-2 S region genes C4 (fourth complement component) and Slp (sex-limited protein) are highly homologous. In males with C4high, Slpa alleles, both proteins are expressed in plasma and the two genes are each transcribed in a single species of mRNA which is indistinguishable in length. The Sk region of the H-2k haplotype carries C4low, Slpo alleles, characterized by very low C4 protein levels in plasma and absence of Slp protein in plasma. We show that mice carrying the Sk region express multiple C4 and Slp mRNAs (RNA doublets) in contrast to mice with any other S region. This represents a genetic polymorphism at the level of RNA multiplicity. The RNA doublets do not result from the use of an alternative upstream initiation site of transcription. We hypothesize that their existence is caused by alternative splicing; however, the use of alternative polyadenylation signals cannot be ruled out. The occurrence of multiple RNA species in strains which carry the C4low, Slpo alleles is possibly related to the very low level of C4 protein expression characteristic for these alleles. PMID- 2575802 TI - Alpha 2-adrenoceptors and platelet function in patients with variant angina. AB - We have previously reported that platelets of patients with variant angina exhibited pronounced hyperactivity to epinephrine, as assessed by aggregation study. To determine whether this is associated with a change in surface alpha adrenoceptor status, we investigated the capacity and affinity of binding sites for [3H]dihydroergocryptine, a potent alpha-antagonist, of platelet lysates prepared from 22 patients with ischemic heart disease and 13 control subjects of similar age. [3H]DHE binding capacity to platelets from control subjects, 6 patients with acute myocardial infarction, 9 with effort angina and 7 with variant angina were 233 +/- 44 (SD), 226 +/- 53, 252 +/- 58 and 348 +/- 48 fmol/mg protein and its affinity were 2.05 +/- 1.40, 0.98 +/- 0.46, 1.59 +/- 0.37 and 1.49 +/- 0.66 nM, respectively. The patients with variant angina had significantly higher capacity of platelet alpha-adrenoceptor than controls (49% increase) or patients with other types of ischemic heart disease. In contrast, the affinity for [3H]DHE was not significantly different as compared with other three groups. Similar increments in the binding capacity for [3H]-rauwolscine, alpha 2 antagonist, were found in platelet lysates prepared from 6 patients with variant angina. These results suggest that increased capacity of platelet alpha adrenoceptor may explain enhanced reactivity to epinephrine in patients with variant angina. PMID- 2575804 TI - Cytochemical localization of a D-amino acid oxidizing enzyme in peroxisomes of Drosophila melanogaster. AB - A peroxide generating oxidase is demonstrated cytochemically in the peroxisomes of adult and larval Drosophila melanogaster, Oregon R and Rosy-506 strains. This enzyme activity is demonstrable using D-pipecolate or D-proline, but not L proline, as substrate and is inhibited by kojic acid. Thus this enzyme shares cytochemical characteristics with vertebrate D-amino acid oxidase. PMID- 2575805 TI - Microtubules, organelle transport, and steroidogenesis in cultured adrenocortical tumor cells. 2. Reversibility of taxol's inhibition of basal and ACTH-induced steroidogenesis is unaccompanied by reversibility of taxol-induced changes in cell ultrastructure. AB - Taxol inhibits the basal and ACTH-stimulated steroidogenesis of cultured mouse adrenocortical tumor cells, presumably by preventing the arrival of cholesterol in mitochondria. In these cells, taxol polymerizes and rearranges microtubules, disperses SER masses, disrupts the Golgi, and impedes the formation of cholesterol-containing lysosomes. However, taxol's alterations in ultrastructure appear likely to permit both a microtubule-based organelle transport proposed to bring mitochondria of unstimulated cells close to alternate sources of cholesterol--the SER and lipid droplets--and postulated ACTH-caused increases in these encounters. Conceivably, taxol may prevent the transfer of cholesterol from the SER and lipid droplets to mitochondria, once the meetings are achieved. To investigate this possibility, we determined the reversibility of taxol's ultrastructural effects and inhibition of steroidogenesis. Primary cultured adrenal tumor cells were incubated for 4 hr with and without ACTH (10 mU/ml). with taxol (50 micrograms/ml), and with ACTH and taxol 50 simultaneously. Some cultures from each set were washed with fresh medium and re-incubated for 1.5 hr. with and without ACTH. Media taken from cultures at the ends of pre- and post washout incubations were analyzed for the presence of secreted steroids. Sample cultures were fixed for electron microscopy at the ends of both incubations. Data derived from pre-washout incubations confirmed previous reports of taxol's ultrastructural changes and inhibition of steroidogenesis. When cells recovered from taxol in the absence of ACTH, the inhibition of steroidogenesis was completely reversed. In the presence of ACTH, ex-taxol-treated cells demonstrated a "rounding up' and an increased steroid production that are characteristic responses to the hormone. However, in all cases, there was a persistence of taxol's alterations in organelle numbers and arrangements. Our findings establish that the ultrastructural effects of taxol which we recorded cannot prevent mitochondria of unstimulated and ACTH-stimulated adrenal tumor cells from gaining cholesterol. They strengthened the possibility that in pre-washout incubations, taxol allowed organelle motility to bring mitochondria adjacent to cholesterol containing SER tubules and lipid droplets, but inhibited steroidogenesis by preventing the cholesterol transfer. Taxol might limit the availability of a protein required for the transfer, an effect not visible in our electron micrographs. PMID- 2575806 TI - Palytoxin acts through Na+,K+-ATPase. AB - Palytoxin is the most potent animal toxin, with a unique structure. The author's group has searched for its mode of action with the following results: 1. Palytoxin (1 pM and less) causes a fast K+ outflow from erythrocytes; 2. Extracellular Ca2+ and borate, and intracellular ATP enhance, but ouabain potently inhibits the palytoxin effects; 3. Palytoxin increases the permeability for Na+ and K+ but not for Ca2+; 4. Palytoxin in comparatively high concentrations (100 nM and above) inhibits Na+,K+-ATPase; 5. Palytoxin can be radiolabeled with 125I. Its receptor is very similar to, but not identical to that of ouabain. A reaction scheme has been delineated which allows an explanation to be obtained for all the known actions of palytoxin. It centers on the hypothesis that palytoxin binds to Na+,K+-ATPase and converts the enzyme or its close vicinity into an open channel with the permselectivity measured on erythrocytes. Patch clamp data from myocytes were obtained in other laboratories. They prove the presence of the predicted palytoxin channel. PMID- 2575807 TI - Traffic of mature lymphocytes into the mouse thymus. AB - The thymus is not generally considered to participate in bi-directional peripheral lymphocyte recirculation. We have demonstrated the entry of peripheral lymph node T cells using transfers between Thy-1 congenic mice. These peripheral T cells that enter the thymus bear an essentially medullary (or peripheral) phenotype and on section stains are confined to the medulla where they constitute 0.2-0.3% of the cells. These cells are remarkable for their frequent expression of the peripheral node homing receptor MEL-14 and for their persistence. Using transferred fluorescent labeled cells we also identify the entry of peripheral B cells into the thymus. Possible roles for peripheral B and T cells in the thymus include participation in thymocyte maturation or selection, the generation of thymic pathology and reactions to thymic pathologic processes. PMID- 2575808 TI - Are CD4+ cells responsible for protection against salmonellosis? Remarks from studies on athymic and thymus-grafted rats. PMID- 2575809 TI - Isolation of Japanese encephalitis virus from mosquitoes collected in Karnataka state, India from 1985 to 1987. AB - Detection and isolation of Japanese encephalitis (JE) virus using mosquito inoculation and immunofluorescence techniques were attempted from female mosquitoes collected in JE endemic areas of Kolar and Mandya districts of Karnataka state, India, from 1985 to 1987. 65,388 mosquitoes consisting of 19 species in 1541 pools were processed. Of these, 18 pools showed the presence of JE virus antigen. JE virus was isolated from 9 pools, 3 of Culex gelidus, 2 of C. tritaeniorhynchus, and one each of C. quinquefasciatus, C. fuscocephala, C. vishnui and Anopheles peditaeniatus. Isolation of JE virus from C. gelidus, C. fuscocephala, C. quinquefasciatus and An. peditaeniatus is reported for the first time in India. PMID- 2575810 TI - Characterization of Leishmania donovani stocks by genomic DNA heterogeneity and molecular karyotype. AB - A hypervariable deoxyribonucleic acid (DNA) probe was isolated by screening a Leishmania donovani genomic DNA library with L. donovani total DNA. The probe was used to characterize L. donovani stocks on the basis of restriction fragment length polymorphisms (RFLPs). The molecular karyotype of the same stocks was examined by orthogonal field alternation gel electrophoresis. On the basis of the observed RFLPs Mediterranean L. donovani infantum and South American L. donovani chagasi stocks were more similar to one another than they were to Indian L. donovani donovani or African L. donovani stocks. This conclusion was also supported by the studies on molecular karyotype. The probe also showed African L. donovani stocks to be heterogeneous in their restriction fragment patterns: the patterns of Indian stocks were, by contrast, relatively homogeneous. Certain L. donovani stocks that appeared to be closely related on the basis of RFLPs and isoenzyme data were markedly different in karyotype, demonstrating the rapidity of chromosome evolution in Leishmania donovani. PMID- 2575811 TI - Enzyme immunoassay for the detection of dengue IgG and IgM antibodies using infected mosquito cells as antigen. AB - The detection of immunoglobulin (Ig)G and IgM antibodies to dengue 1 virus was studied by a simple enzyme immunoassay, in which infected cultured cells infected with dengue virus were used as antigen (EIA-ICC). Detection of anti-dengue 1 IgG by EIA-ICC was correlated with haemagglutination assays. EIA-ICC anti-dengue 1 IgM detection was less sensitive than IgM capture enzyme-linked immunosorbent assay. IgG and IgM responses in dengue 1 infection were studied by EIA-ICC, using sera collected at different intervals after onset of illness: IgM and IgG appeared on the 4th day of disease; the highest IgM mean titres were detected on the 7th day and IgM was not detected in sera obtained after the 60th day; the highest mean titres of anti-dengue 1 IgG were seen in sera obtained between 22 and 30 d after onset of illness. EIA-ICCs for 6 flaviviruses and 1 alphavirus were conducted with sera from patients infected with dengue 1, and primary and secondary infections of other flaviviruses. The results showed that anti-dengue 1 IgG detection was sensitive, and the antibodies were cross-reactive among the flaviviruses. Anti-dengue 1 IgM detected in dengue 1 patients was mostly type specific. The pattern of secondary dengue infection, i.e. the presence of IgG and a low titre or absence of IgM antibodies, was observed in the sera of 6 patients obtained in the first week after onset of illness. EIA-ICC is useful for dengue diagnosis, surveillance and sero-epidemiological studies. PMID- 2575814 TI - Peripheral blood T lymphocyte subpopulations in patients with tuberculosis and the effect of chemotherapy. AB - Peripheral blood T lymphocytes and their subsets were determined in 30 patients with pulmonary tuberculosis (15 smear positive and 15 smear negative) and 11 healthy individuals. All patients were assessed clinically, radiologically, bacteriologically and by tuberculin testing, and their lymphocyte counts were repeated after completion of 3 months chemotherapy. The mean ratio of putative helper/suppressor T cell subsets (CD4/CD8) of healthy individuals was 1.8 (range 1.1-2.5). These ratios were independent of tuberculin reactivity and were unaffected by BCG vaccination. In both smear positive and smear negative patients there was a reduction in the total T cell and CD4 counts and an increase in the CD8 count, with a concomitant reduction in the CD4/CD8 ratio. Following successful chemotherapy, the mean CD4/CD8 ratios reverted from 0.82 to 1.57 in smear positive patients and 0.88 to 1.52 in smear negative patients, these being near normal values. PMID- 2575813 TI - A game with shifting mirrors. PMID- 2575812 TI - Novel antihypertensive drug reveals unexpected complexities in beta-adrenoceptor pharmacology. PMID- 2575815 TI - Activation of a ribosomal S6 protein kinase in rapidly emerging diethylnitrosamine-induced gamma-glutamyltranspeptidase-positive hyperplastic liver lesions of the rat. AB - The gamma-glutamyl transpeptidase (GGT)-positive hyperplastic liver lesions which developed in the Fisher 344 rat 7 and 60 days following a single carcinogenic dose of diethylnitrosamine (DENA, 200 mg/kg body weight), short-term dietary exposure to 0.02% 2-acetylaminofluorene (AAF) to suppress the growth of normal hepatocytes, and partial hepatectomy to actuate rapid growth of DENA altered hepatocytes not suppressed by AFF, showed an increased activity of a kinase which specifically phosphorylates the ribosomal S6 protein in vitro. Sham-operated animals showed, on the contrary, no GGT-positive cells and low S6 kinase activity, under the same conditions. After partial hepatectomy, activation of S6 kinase and elevated levels of phosphorylated S6 protein in vitro were detected in the early phases of "normal" hepatocyte proliferation, during liver regeneration, in DENA-treated, GGT-negative preparations, when the "selection" agent AAF was omitted from the diet. The observed activation of S6 kinase in GGT-positive hepatocytes and/or liver nodules could represent an early manifestation of the enhanced proliferation of altered hepatocytes during tumor induction and/or promotion under these conditions. PMID- 2575816 TI - Detection of the 170 kDa P-glycoprotein in neoplastic and normal tissues. AB - A membrane purification procedure and an immunoblotting assay have been designed to allow screening of human solid tumors for overexpression of the GP170 glycoprotein without employing a disaggregation method to obtain cell suspensions. The electrophoresed membrane proteins were probed, after Western Blotting, with the C219 monoclonal antibody and iodinated Protein A. The labeling intensity of the bands on the autoradioimmunoblots were quantified by densitometry. To test for the presence of GP170, we used membranes from the UV 2237 fibrosarcoma line and its adriamycin-resistant variant ADMR, grown in vitro or as solid tumor in mice. Membranes of human normal and tumor tissues obtained from previously untreated patients were also tested. An immunoreaction was observed in the adriamycin-resistant UV 2237 lines grown in vitro or in vivo. Quantitatively, the binding of the resistant cell line grown in vitro was higher than that observed in cells grown in mice. Bands in the GP 170 region were observed in 4/7 normal and in 7/7 tumor colon tissues and in the normal medulla from 2 patients with cancer of the renal cortex. No reaction could be found in samples from normal tissue, primary tumor or nodal metastasis from 7 patients with breast cancer. PMID- 2575817 TI - Zinc phosphide ingestion: a case report and review. AB - We present the case of a patient who attempted suicide by ingestion of the rodenticide zinc phosphide. Zinc phosphide manifests its immediate toxicity through production of phosphine gas. Signs and symptoms of toxicity include nausea, vomiting, dyspnea, and changes in mental status; immediate death results from pulmonary edema. Delayed effects are secondary to the absorption of phosphide, affecting primarily the liver, heart and kidneys. Delayed deaths are related to a direct cardiotoxicity. Treatment is mainly symptomatic and supportive; aggressive airway management and circulatory support are critical to a successful outcome. PMID- 2575818 TI - Circadian variation in the mitotic rate of the rat corneal epithelium. Cell divisions and migration are analyzed by a mathematical model. AB - A stathmokinetic method was used to study the diurnal variation in the mitotic rate (MR) of the rat corneal epithelium, and in the adjacent conjunctival epithelium. A prominent circadian variation in cell proliferation was observed in both epithelia, both showing almost the same pattern, which may indicate that both tissues are submitted to the same regulatory mechanisms. The average rate of cell renewal during a 24 h period indicated a mean cell renewal time of 12.3 days. This is longer than previously assumed. The MR declined toward the central cornea. Based on the above observations and the known centripetal migration of cells in the corneal epithelium, we have developed a mathematical model showing isomorphism with the renewal of the corneal epithelium. PMID- 2575819 TI - Flow DNA-cytometric findings of paraffin-embedded primary cutaneous melanomas related to prognosis. AB - In a retrospective study flow cytometry was performed in 82 paraffin-embedded clinical stage I cutaneous melanomas. A significant correlation of ploidy to melanoma thickness was found. Using a log rank test ploidy was found significant for prognosis. However, using the Cox's proportional hazard test the influence of ploidy vanished and melanoma thickness or Clark level of invasion together with sex and location were the factors most important for prognosis. PMID- 2575820 TI - Computer aided cytometry in high grade malignant non-Hodgkin's lymphomas and tonsils. AB - The aim of the study is to establish quantitative cytological criteria for reliable diagnoses in high grade malignant non-Hodgkin's lymphomas (NHL). For this purpose Pappenheim-stained cytologic imprints from 15 cases of high grade malignant NHL and ten cases of chronic tonsillitis have been analysed using a TV microscope system, high resolution color scanning (13.3 pixel/microns), and image processing on a computer. The highly reliable computer-extracted cell features can be used to discriminate the different cell types of malignant NHL. Because of a considerable overlap, no feature on its own is sufficient to discriminate all the different cells. Only multivariate analysis of a suitable combination of features allows reliable discrimination. The results show that the different cells defined by subjective morphological criteria in the Kiel-classification of malignant NHL also form distinctive subpopulations with regard to their objective mathematical cell features and show distinctive differences when compared with their benign counterparts derived from reactive lymphatic tissue. PMID- 2575821 TI - The distribution of endocrine cells along the mouse small intestine. Bombesin and somatostatin producing cells. AB - The topographical distribution and incidence of endocrine cells in the crypt and villus epithelium and along the length of the mouse intestine was studied. Cells containing somatostatin and bombesin like reactivity were stained by immunocytochemical techniques using polyclonal antiserum. Most of the somatostatin cells were found in the duodenum, jejunum and ileum, and these cells were generally more frequent on the villus compared to the crypts. This may indicate that the somatostatin cells develop late in the endocrine cell lineage. Bombesin like cells were rare in occurrence, and were only present in measureable numbers in the ileum, where they were observed in the crypt and villi. The application of ELISA assays to determine the specificity of the antisera for these peptides is also discussed. PMID- 2575822 TI - Synaptophysin and chromogranins/secretogranins--widespread constituents of distinct types of neuroendocrine vesicles and new tools in tumor diagnosis. AB - Normal and neoplastic neuroendocrine (NE) cells have been identified for many years by morphological criteria only. With the advent of immunocytochemistry, antibodies against NE-specific polypeptides have been used to identify NE cells that had been missed by conventional techniques, thus improving the diagnosis of NE cells. In this review article we discuss (i) the biochemical, cell biological and molecular biological data obtained so far for two major types of NE markers, synaptophysin, which is characteristic of the small "transparent-looking" neurosecretory vesicles, and the chromogranins/secretogranins, which are widespread constituents of the larger "dense-cored" secretory granules; (ii) the immunohistochemical data obtained for these marker proteins in normal and neoplastic human NE cells and tissues; and (iii) future possible developments involving these as well as other proteins that are associated with these two distinct secretory organelles of NE cells and may serve as potential markers in NE cell diagnosis. PMID- 2575823 TI - Sustained cytopenia after leukapheresis for collection of peripheral blood stem cells in small children. AB - Marked and persistent cytopenia was observed in two 3-year-old children with cancer, after lymphopheresis to collect peripheral blood stem cells (PBSC) for autotransplantation after high-dose chemotherapy. This finding suggests that PBSC are a major component of the hematopoietic cells in small children and, hence, that special care is necessary in the construction of a protocol for collection of stem cells from young children. PMID- 2575825 TI - Synthetic peptide immunoassay for diagnosis of HIV 2 infection. PMID- 2575824 TI - Autoantibodies against CD4- and CD8-positive T lymphocytes in HIV-infected hemophilia patients. AB - The presence of IgG, IgM, C3d, or gp120 on the surface of T lymphocytes was analyzed by flow cytometry in blood samples from 73 hemophilia patients and 56 healthy controls. IgG and IgM autoantibodies against CD4+ lymphocytes were found in HIV + patients but not in HIV-patients or healthy controls (p less than 0.001). IgM autoantibodies were more frequent than IgG autoantibodies. Autoantibody formation increased with disease progression. However, within the same disease risk category, patients with autoantibodies were not "more immunologically abnormal' than patients without autoantibodies. HIV + patients who possessed autoantibodies had similar CD4+ and CD8+ lymphocyte counts as HIV + patients without autoantibodies. There was no significant difference in the number of patients with abnormal CD4/CD8 ratios, serum neopterin levels, or in vitro responses to allogeneic stimulator cells or mitogens between autoantibody positive or -negative patients of the same risk category. Our data suggest that autoantibodies against CD4+ lymphocytes may be helpful as indicators of disease progression, however, their immunopathogenetic role remains unclear. PMID- 2575826 TI - Diagnosis and prevalence of HIV-2 antibodies in different population subsets in The Netherlands. AB - A serum panel obtained from male homosexuals (n = 278); i.v. drug abusers (n = 99), patients attending a VD clinic (n = 390), blood donors who visited Central or West Africa (n = 573), blood donors who had sexual contact with natives from Central or West Africa (n = 38), blood donors from Surinam, South America (n = 481), individuals positive for anti-HIV-1 (n = 94), individuals with indeterminate HIV-1 western blot (WB) reactions (n = 73), African patients with AIDS or AIDS-related symptoms (n = 30), and random Dutch blood donors (n = 555), was tested with HIV-2 ELISA (ELAVIA-2). Of these 2,611 samples, 32 (1.2%) were repeatedly reactive. Antibodies to gp140/105env were found in 4/32 by HIV-2 WB, and in 1/4 by radioimmunoprecipitation (RIPA). These 4 HIV-2 WB-positive samples were also reactive with gp160/120env in HIV-1 WB, suggesting cross-reactivity. In a spot test with synthetic peptides of the transmembrane glycoprotein of both HIV types, 3/4 were only HIV-1 positive and 1/4 was strongly HIV-2 positive and weakly HIV-1 positive. In inhibition assays with soluble HIV-1 or HIV-2 synthetic peptides in HIV-1 and HIV-2 peptide ELISA, cross-reactivity was excluded, which indicates an HIV variant or HIV-1/HIV-2 double infection. It is concluded that for the moment HIV-2 infection is at low prevalence in risk groups in The Netherlands, and that in addition to WB and RIPA, synthetic peptide assays are useful for differentiation between HIV-1 and HIV-2 antibodies. PMID- 2575827 TI - [Clinico-immunologic evaluation of the efficacy of bikarfen in allergic dermatoses]. AB - It was found that the new native antihistamine and antiserotonin drug bicarphen possesses in patients with allergic dermatoses (eczema and neurodermatitis) more active antihistaminic, anti-inflammatory, antipruritic and antiallergic properties than commonly used drugs, particularly in cases with prevalence of exudative and allergic reactions of the immediate type. Normalization of rosette forming T-lymphocytes and A and G immunoglobulins was essential. PMID- 2575829 TI - Nitric oxide and cytosolic guanylate cyclase: components of an intercellular signalling system. AB - Endothelial cells, neutrophils, macrophages, and probably various other cells synthesize nitric oxide or a labile NO-containing compound from L-arginine. NO and various NO-containing compounds activate the cytosolic guanylate cyclase, which catalyzes the formation of the second messenger cyclic GMP. This cyclic nucleotide is involved in the regulations of certain target cells as vascular smooth muscle and platelets. Thereby, NO or a labile NO-containing compound and the cytosolic guanylate cyclase are components of an intercellular signalling system. PMID- 2575828 TI - Long-term prognostic value of serum bile acids in liver cirrhosis: a prospective study. AB - The long-term prognostic significance of serum bile acid (SBA) levels in liver cirrhosis was prospectively evaluated in a 3-year follow-up of 111 patients. The predictive value of SBA levels, of Child classification, and of some commonly used clinical and laboratory parameters were compared analyzing the survivorship functions by means of Life-table method and chi-square Logrank test. SBA determinations showed a high prognostic significance, comparable with the one of the multiparameteric Child classification and significantly higher than the ones of any considered single clinical or laboratory parameter. SBA levels by themselves seem therefore to be of some value in establishing an approximate survivorship prediction in liver cirrhosis, thus representing a possible alternative to multiparametric predictive models in routinary clinical practice. PMID- 2575830 TI - Endothelium-dependent regulatory mechanisms in human coronary bypass grafts: possible clinical implications. AB - The internal mammary artery and saphenous vein are used as grafts in patients undergoing coronary bypass surgery. Different biological properties of arterial and venous grafts might contribute to the better graft function, lower patient mortality and higher patency rate of the mammary artery. We investigated the role of endothelium-derived relaxing factor (EDRF), which is a vasodilator and inhibitor of platelet function, in arterial and venous grafts. In mammary arteries, acetylcholine, thrombin, adenosine diphosphate, histamine and the calcium ionophore A23187 evoked endothelium-dependent relaxations blocked by hemoglobin or methylene blue, but not by cyclooxygenase inhibitors delineating EDRF as the mediator; in vascular smooth muscle cells, this was associated with a rise in intracellular cyclic GMP. Exogenous nitric oxide evoked potent endothelium-independent relaxations. In the saphenous vein, endothelium-dependent relaxations to all agonists, except the calcium ionophore, were weak, indicating heterogenous endothelium-dependent vascular reactivity as compared to the artery. The mammary and saphenous vein exhibited an enhanced sensitivity to nitric oxide. The greater release of EDRF in the internal mammary artery, particularly in response to platelet derived products, could contribute to the higher patency rate of arterial as compared to venous grafts and give new insights into mechanisms involved in graft function and vascular occlusion in man. PMID- 2575831 TI - Extragenic factor IX gene RFLP is useful for detecting carriers of Japanese hemophilia B. AB - Seventy-eight X chromosomes from 25 normal Japanese subjects and 22 family members with hemophilia B (coagulation factor IX deficiency) were examined with an extragenic factor IX DNA probe, pX58dIIIc at DXS99 locus. In contrast to the previously described nonpolymorphic RFLPs in the factor IX gene, DXS99 locus RFLP produced by SacI digestion was detected among those Japanese subjects with allelic frequencies of 0.48 and 0.52. The estimated heterozygosity rate of this extragenic RFLP among Japanese females was about 50%. The study of hemophilia B family members showed that DXS99 locus RFLP was informative in 9 out of 13 families tested (69.2%). No recombination events between the factor IX gene locus (F9) and DXS99 locus have been noted among nine families analyzed. DXS99 SacI RFLP is a useful gene indicator of carrier-ship of hemophilia B. PMID- 2575832 TI - Selective vulnerability of pigmented dopaminergic neurons in Parkinson's disease. AB - From a neuropathological point, the diagnosis of Parkinson's disease is confirmed by a neuronal cell loss and the presence of Lewy bodies in the substantia nigra. In Parkinson's disease, the precise type of nigral neuron which degenerate still remains unknown. Are all types of neuron similarly injured, are only subpopulations of neurons vulnerable? In an attempt to answer the question, a qualitative and quantitative analysis of the distribution of dopaminergic cells, as identified by immunohistochemistry with a specific antibody against tyrosine hydroxylase, was performed in the ventral mesencephalon of control subjects and patients who died with a clinical diagnosis of Parkinson's disease. In control brains, two types of catecholaminergic neurons were evidenced; some contain visible-neuromelanin, others do not. In patients with Parkinson's disease, the tyrosine hydroxylase positive cells which contained the pigment were the most vulnerable. PMID- 2575834 TI - [Studies on the analysis of some narcotic analgesics and CNS-stimulants]. AB - Procedures for the separation and identification of 12 narcotic analgesics and 2 CNS-stimulants are described using GC/FID, GC/NPD and GC/MSD. The TFA and TMS derivatives were prepared by adding TFAA, MB TFA and MSTFA to the standard drugs. The mixture was heated at 70 degrees C for 30 min and chromatographed on FS capillary columns (SE-54, HP-5). Preliminary results show that all the derivatization with TFAA is better than that with MBTFA, but not much different from MSTFA derivatization. The method is reliable, fast and simple and may be used to screen these drugs and further applied to the analysis of biological fluids such as plasma and urine. PMID- 2575833 TI - Effect of beta-receptor blockers on uterine contractility in a puerperal model. AB - beta-receptor blockers are increasingly used in the treatment of pregnancy induced hypertension. Hitherto an oxytocic effect on the myometrium could not be excluded. We investigated the effect of 0.8 resp 1.6 mg pindolol on uterine activity in a double blind study in comparison with a placebo group, using a puerperal model. A "paradoxical" decline in uterine activity could be demonstrated, speaking in favor of a further propagation of beta-blockers in obstetric practice. PMID- 2575835 TI - Determination of taxol in the extract of taxus chinensis by reversed phase HPLC. PMID- 2575836 TI - [The blocking and partial agonistic actions of jatrorrhizine on alpha adrenoceptors]. AB - Jatrorrhizine (Jat) competitively antagonised the effects of phenylephrine on rabbit aortic rings and clonidine on electrically stimulated rat vas deferens with pA2 values of 5.73 and 5.86, respectively. It (5 mg/kg iv) also diminished the pressor responses induced by either thoracic sympathetic stimulation (T7-T9) or noradrenaline (2 micrograms/kg iv) in pithed rats. Furthermore the dose response curves for methoxamine and B-HT 920 were shifted parallely to the right by iv Jat 10 mg/kg. Below 1 mumol/L, Jat alone showed the depression of the contraction of rat vas deferens stimulated electrically. This effect, however, was less evident at higher concentrations of Jat and was reversed by yohimbine (0.1 mumol/L). Similarly, at very low concentration (1 nmol/L), Jat shifted the dose-response curves for clonidine parallely to the left. In pithed rats, the increase of heart rate evoked with electrical stimulation of spinal segment (C7 T1) was attenuated by Jat (1 mg/kg) and clonidine (30 micrograms/kg), but argumented by large doses of Jat (10 mg/kg) and yohimbine (50 micrograms/kg). The above results showed that: firstly, Jat has blocking actions on both alpha 1- and alpha 2-adrenoceptors, which may be relevant to its hypotensive and anti arrhythmic actions; secondly, the demonstration of dualistic actions of Jat on adrenoceptors, which has never been documented before, may be also present in other homologues of the protoberberines. PMID- 2575837 TI - Prevention of postischemic reperfusion damage on isolated working rat hearts by bopindolol and propranolol. AB - Reperfusion after 30-min regional or global ischemia of the isolated working rat hearts did not restore the cardiac functions (as measured by cardiac output and power production), but exacerbated the existing damages. The lipid peroxidation product malondialdehyde (MDA) in the regional and global ischemic-reperfused myocardium increased by 37.6 and 45.2%, respectively. Bopindolol 0.1 mumol/L and propranolol 10 mumols/L protected the myocardium against the postischemic reperfusion damages, accelerated the recovery of cardiac functions during reperfusion and decreased the MDA content in the ischemic-reperfused myocardium. It is postulated that the prevention of cardiac cells from lipid peroxidation injury is related to the protection afforded by the drugs to the ischemic reperfused hearts. PMID- 2575838 TI - [Effects of xylazole on heart rate and blood pressure in conscious dogs]. AB - Xylazole (Xyl) is an analogue of xylazine (Xyn) synthesized by Lanzhou Institute of Chinese Traditional Veterinary Medicine. The effects of Xyl on heart rate and blood pressure were studied in 5 conscious dogs. Xyl 1 mg/kg iv was similar to Xyn in producing bradycardia and an initial transient hypertension followed by a lasting hypotension which was less significant than Xyn. Yohimbine (0.1 and 0.3 mg/kg), an alpha 2-adrenoreceptor blocking agent, antagonized bradycardia and hypotension induced by Xyl. Tolazoline (3.3 mg/kg), a nonselective alpha adrenoreceptor blocking agent, reversed the bradycardia and hypotensive effect. Prazosin (1 mg/kg), an alpha 1-adrenoreceptor blocking agent, did not change Xyl induced bradycardia and hypotension. Atropine (20 micrograms/kg) not only antagonized Xyl-induced bradycardia but also changed from bradycardia to tachycardia, and greatly potentiated Xyl-induced hypertension for more than 30 min. The results suggested that Xyl-induced cardiovascular effects are similar to Xyn that mediated by alpha 2-adrenoreceptor. PMID- 2575839 TI - Organic and inorganic calcium blockers on voltage and receptor operated channels of resistance arteries of the rat. AB - The vasoconstrictor responses induced by noradrenaline (NA), adrenaline (AD), serotonin (ST) and vasopressin (VP) on the anterior mesenteric artery of the rat and its branches, were maintained, although somewhat reduced when perfused with a Ca free solution that depletes extracellular Ca. The vasoconstrictor responses were abolished when Lanthanum, EDTA, Verapamil or Nifedipine were added to the Ca free solution. These drugs are known to displace plasmalemmal bound Ca that triggers vasoconstriction when the agonists attach to the receptors thus blocking the vasoconstrictor responses. When the mesenteric arteries were perfused with a Ca containing solution, to block the vasoconstriction induced by the agonists the concentration of La3+, EDTA, Verapamil and Nifedipine must be raised. Thus these drugs appear to compete with extracellular ionic Ca for the membranal sites involved in the activity of the agonists. K induced vasoconstriction was abolished when extracellular Ca was depleted by a Ca free solution and with lower concentrations of the anticalcic drug than those used to cancel the effect of the agonists. Ca appears to be attached to voltage operated channels less firmly than to receptor operated channels. NA, AD, ST and VP showed different sensitivity to the blocking effect of the various anticalcic drugs. This is probably explained by small differences in the structure of the Ca channels operated by the agonists. PMID- 2575840 TI - Glucagon secretion and alpha-cell sensitivity to somatostatin in genetically diabetic mice C57BL/KsJ-mdb. AB - In previous studies in C57BL/KsJ mdb/mdb mice, we observed alterations in glucose induced insulin secretion in vitro, and a defective inhibitory effect of somatostatin on insulin secretion. In this work we studied glucagon secretion patterns under arginine-glucose stimulation, in perifused pancreatic slices from genetically diabetic mice aged 20 to 90 days. We also explored whether alpha cells present a diminished sensitivity to somatostatin. Results showed that: a) in mdb/mdb mice aged 20 to 90 days, glucagon secretion patterns exhibited basal hypersecretion and a diminished first peak; b) somatostatin inhibited stimulated glucagon secretion below baseline values in mdb/mdb mice aged 20 to 30 days. In later stages (40 to 90 days), somatostatin exerted a lower inhibitory effect since glucagon levels remain above basal values. This could indicate a progressive impairment in alpha-cell sensitivity to somatostatin, as it was previously observed in beta-cells. PMID- 2575841 TI - Effects of intravenous calcitonin gene-related peptide (CGRP) on local blood flow in the cat. AB - The effects of i.v. calcitonin gene-related peptide (CGRP) on regional blood flow, vascular resistance, heart rate and cardiac output in cats were studied using the microsphere method. Three series of experiments were performed. In the first there was no pre-treatment of the animals. In the second the animals were pre-treated with indomethacin (5 mg kg-1) in order to prevent the formation of prostaglandins. In the third series the ganglionic blocking agent hexamethonium bromide (80 mg kg-1) was given in order to prevent autonomic reflexes. CGRP was given as an i.v. infusion. Two doses were tested in each series. Animals with no pre-treatment and those pre-treated with indomethacin received first 60 pmol kg-1 infused over a 5-min period and then 180 pmol kg-1 infused over a 3-min period. Animals under ganglionic blockade received the same dose as the total infusions in the other series (240 pmol kg-1) infused over 4 min and a second infusion of 1.2 nmol kg-1 over 5 min. Vasodilatory effects were observed in most of the tissues tested, but there were marked differences in sensitivity. The most sensitive tissues seemed to be the lacrimal, submandibular and parotid glands, the nictitating membrane, the tongue and the gallbladder. The patterns of sensitivity were similar in all the series, indicating that neither prostaglandins nor autonomic reflexes were involved in the effects. In experiments with animals under ganglionic blockade, an increase in blood pressure, concomitant with an increase in heart rate, was seen 5 min after the infusions ended. Thus, it is likely that the peptide exerts a direct positive chronotropic effect on the feline heart. PMID- 2575842 TI - Cardiovascular responses to intravenous calcitonin gene-related peptide (CGRP) in the albino rabbit. AB - The regional sensitivity of different vascular beds to i.v. CGRP was investigated in the albino rabbit by using the microsphere method. Experiments were performed without pre-treatment on both conscious and pentobarbital-anaesthetized animals. In addition, in one series on conscious animals, rabbits were pre-treated with indomethacin in order to reduce the formation of prostaglandins. In another series, anaesthetized rabbits were subjected to ganglionic blockade with hexamethonium bromide in order to abolish reflexes involving the autonomic nervous system. 120 pmol kg-1 of CGRP was given to all the animals, the conscious animals receiving the peptide in one infusion lasting 4 min. In the anaesthetized animals, the dose was divided into first a 5-min infusion of 30 pmol kg-1 followed some minutes later by a 3-min infusion of 90 pmol kg-1. The most pronounced vasodilatory effects were seen in the pancreas, gallbladder, stomach, duodenum, tongue, teeth and the conjunctiva/nictitating membrane. In some series marked effects were also seen in the dura mater, choroid plexus and some parts of the brain. In the anaesthetized animals almost no statistically significant effects on local blood flows were seen following the first, smaller, dose, but following the larger dose more pronounced effects were observed. Pre-treatment with indomethacin did not to any great extent affect the responses, which contradicts the involvement of prostaglandins. The pattern of the responses was unaffected by the ganglionic blockade, but the variability of response was reduced. In conclusion there are great regional variations in the sensitivity to circulating CGRP. The patterns shows a resemblance to that obtained in other species, but there are some marked differences, The tissues most susceptible to the peptide are those easily exposed to noxious stimuli and containing CGRP in the sensory nerve endings, observations in agreement with the proposed role for the peptide in neurogenic defence mechanisms. PMID- 2575843 TI - Temperature dependence of 'local' and 'upstream' regulation of sympathetic transmitter secretion in mouse vas deferens. PMID- 2575845 TI - Individual variations in potency of alpha,beta-methylene ATP as inhibitor of the excitatory junction current in mouse vas deferens caused by sympathetic nerve stimulation. PMID- 2575844 TI - Is 'upstream' control of sympathetic transmitter release dependent on the length of varicosity strings? PMID- 2575846 TI - [Synthesis of new aminoalkanol derivatives of benzofuran with potential beta adrenolytic activity]. AB - Two routes of synthesis of 2-acetyl-7-hydroxy-6-methoxy-3-methylbenzofuran and some of its aminoalkanol ethers are described. Six compounds proved to exert the expected antiarrhythmic and hypotensive effects. PMID- 2575847 TI - [Analysis of 5-pyrazolinone derivatives in pharmaceutical products. I. Spectrophotometric analysis of two-component drugs containing propyphenazone]. AB - Two new methods for the determination of active components in the preparations Gardan P (propyphenazone + noramidopyrine) and Pabialgin P (propyphenazone + allobarbital) have been elaborated. The first one is a direct spectrophotometric method based on measurements of absorption at two wave lengths; at lambda = 218 and 270 nm for Pabialgin P, and at lambda = 232 and 260 nm for Gardan P. The second method, the chromatographic-spectrophotometric method has been based on separation of individual components by thin-layer chromatography followed by their spectrophotometric determination. The results obtained by the above two methods were compared with the results given by the titrimetric method according to the producer's standard. Statistic analysis by the Student's and F-Snecodor's tests has shown that all these methods are equally precise but differ in accuracy, sensitivity and selectivity. The spectrophotometric determination of allobarbital has proved to show the highest accuracy (Wz = 1.4), while the acidimetric determination of propyphenazone in the non-aqueous medium has appeared least accurate (Wz = 3.7). Sensitivity of the tested methods was found to range from 3 x 10(-4) g/cm3 for the titrimetric methods to 6 x 10(-6) g/cm3 for direct spectrophotometric measurements. In respect of selectivity, only the chromatographic-spectrophotometric method has proved to be enough selective and to give quite correct results. PMID- 2575848 TI - Roles of calcium in the regulation of tyrosine hydroxylase. PMID- 2575849 TI - Loss of suppressor-inducer T-cells in chronic-progressive multiple sclerosis: preliminary results. PMID- 2575850 TI - Lymphocytic choriomeningitis virus-specific delayed-type hypersensitivity reaction in mice. PMID- 2575851 TI - [A new general orthopedic universal intramedullary nail for the tibia. Clinical development and experiences]. AB - The new AO-Universal-Nail was developed through intensive cooperation between fundamental research, technicians and clinical application. We are now able to transfer the concept of a Universal-Nail (initially for the femur) to the tibia as well. The existing technique of the medullary nail was maintained as far as possible. Special features to be highlighted: The new AO-bend obtains better impact behavior and a more anatomical stabilization of the bone cavity. The tapered tip eases the gliding of the tip of the nail along the inner wall of the dorsal corticalis and past the fracture. Proximal locking is obtained through three transverse extending holes. They offer many choices for optimal placement of the locking bolts. Interlocking from anterior to posterior has been logically abandoned, due to danger for nerves and vessels. Distal looking offers a large selection for stabilization through one a.p.-hole and two transverse holes for the locking bolts. The design from anterior to posterior entables the protection of the soft tissue. The Universal-nail can either be inserted with or without interlocking. A free decision is possible during the operation. The new AO Universal-Nail for the tibia (as for the femur) maintained reliable aspects and was consequently converted to meet new demands and findings. The basic fundamentals of the AO, namely the observance and application of biomechanical principles and safe operation procedure were attained through simple instrumentation and have been proved successful for clinical application. PMID- 2575852 TI - [A treatment concept using external transfixation in unstable defect trauma of the knee joint]. AB - The main problems in the treatment of severe knee injuries with extensive soft tissue damage, ligamentary lesions and compound fractures consist in the high risk of infection and complex instability of the joint. 20 patients suffering such type of trauma were treated by a schedule comprising an extensive debridement and a combination of minimal internal osteosynthesis and external transfixation. Secondary operations were always performed as a second look in all patients and various surgical reconstructions of the soft tissue coverage under continuous protection of the external fixation. Most patients obtained satisfactory functional results, only 2 cases ended up with arthrodesis due to deep infection. PMID- 2575853 TI - [Preclinical and clinical primary therapy of multiple fractures of the leg]. AB - A successful clinical primary treatment of multiple fractures of the lower extremities depends on a rapidly administered preclinical therapy with short care periods. The early biomechanically stable osteosynthesis leads to improved haemodynamics by haemostasis and elimination of pain. Early functional treatment and hypostasis therapy will promote the prophylaxis of pneumonia. 14 patients with multiple fractures of the lower extremities were treated by the concept that provides for preclinical emergency therapy and clinical primary treatment as a unit. PMID- 2575854 TI - [Management of femur shaft fracture in the growth age with the fixateur externe]. AB - Non-operative management is still the treatment of choice today for femoral shaft fractures in children. Indications for operative intervention would include: - the child with multiple injuries, particularly with severe head injuries, in those patients with severe soft tissue damage associated with the fracture; in cases where the reduction is difficult to maintain, as in subtrochanteric fractures; and in children who are not suitable for management with traction. Since 1984, 16 children have had their femoral shaft fractures stabilized by external fixation (Monofixateur) here in the Trauma Department of the Hannover Medical School. The mean age of the patients was 10.3 years (seven to sixteen years). All cases were closed fractures with mild or moderate soft tissue damage. Eleven of the patients had a multiple injury, and four had subtrochanteric fractures. The external fixation remained in place for a mean of 63 days in those patients exclusively treated by this method. In four of the earlier cases there was a Schanz's screw infection and three of these required removal of the external fixation and treatment in a hip spica. After modifying the technique of Schanz's screw insertion, no further infections were seen. Fourteen of the sixteen children were reviewed, with a mean follow up of 21.7 months. None of the children who had been completely managed by this fixation had any clinically relevant malalignment. Six cases had leg lengthening of up to two centimetres. Leg length differences were seen more frequently and more severely in those cases where external fixation was delayed. PMID- 2575855 TI - [Developments in the treatment of fractures of the coxal end of the femur]. AB - The therapeutic concept for proximal femur fractures has changed to varying degrees from 1978 to 1988 in the Department of Traumatology and Reconstructive Surgery at Steglitz Medical Center. In general, conservative therapy has been abandoned. Alloplastic joint replacement is performed in patients with coxarthrosis in the fracture area. A head prosthesis is chosen for those with a life expectancy of less than eight years. Clearly favourable results have been achieved in our department with the Duokopf prosthesis. Patients with a higher life expectancy are submitted to a total hip endoprosthesis, preference being given in cases of collum femoris fractures to the combination of a Spotorno shaft and a Morscher acetabulum. Loading should only be partial for five weeks in patients treated with this cement-free total endoprosthesis. We use the Duokopf prosthesis in the combination of a Spotorno shaft with a Uni-Hip head. We submit these patients to full loading primarily. --We have completely abandoned Ender nailing. We prefer the dynamic hip screw for per- and intertrochanteric femur fractures. For subtrochanteric femur fractures, we use the condyl plate. For lateral collum femoris fractures we have used the four-hole angle plate until 1988. Since 1989 we also use the dynamic hip screw. The one-hole angle plate is used for osteosynthesis in cases of medial collum femoris fractures. PMID- 2575856 TI - [Differential diagnosis of shoulder dislocation with special reference to posterior dislocation]. AB - Evaluation of a dislocated shoulder must classify the direction of dislocation and describe additional injuries as well as the recurrence rate. This is required in all types of dislocations by recording the case history in detail, and by examining the shoulder clinically as well as radiographically in two planes. Ultrasound and arthro-computer tomography are valid methods to demonstrate injuries of bony and ligamentous structures. They may therefore influence surgical treatment. In posterior dislocation of the shoulder quite often early diagnosis is missed. If this injury is suspected, careful clinical and radiographical evaluation is most important. PMID- 2575857 TI - [Resorbable implants and their use exemplified by fracture of the head of the radius]. AB - First a short survey of the variety of experiments concerning absorbable implants is given. The result of those experiments, especially with large implants are still quite unsatisfactory. For small osteosynthesis the development of Polydioxanon-Pins seems to open new perspectives of therapy. Also some selected indications in the field of hand surgery as well as maxillary surgery are mentioned. Promising characteristics of PDS-Pins, such as gentle application, complete absorbability, no late infections and no removal of metal plates, made us implant these pins in eight patients aged 35 to 58 suffering from radial head fractures (type Ib and Ic according to Vogt). Early functional treatment showed very good results. Two exemplary cases are illustrated. PMID- 2575858 TI - [Instability of the wrist joint--diagnosis and therapy]. AB - Wrist-joint instability can be caused by injuries to ligaments or bones, it can be intermittent or permanent. Clinical symptoms and pain sensations are non characteristic. The X-ray findings are the clue to the diagnosis. In this article recommendations are given for exact X-ray positions of the hand and their evaluation. The classification of instability is corresponding to the X-ray findings. Further investigations like radiographs under stress, dynamic investigations or the arthrography of the wrist-joint can be helpful to find out the exact pathologic changes. They are variable and are ranging from dysharmonic movement to a complete destruction of the carpal bones. Treatment is according to the pathologic changes and their causes. Fresh ligamentous injuries (e.g. additional injuries to a Colles' fracture or a perilunate luxation) should not be discarded lightly. Most cases we saw presented very late, the patients showed already osteoarthritic changes of the carpal bones with destruction of the cartilage. The late results of ligamentous reconstructions have not fulfilled their expectations, the current trend is towards a partial arthrodesis of the carpal joints in order to reconstruct the joint stability under preservation of partial mobility. This method of treatment has certain disadvantages: Pathologic wrist-joint movements, impingement syndromes and undue stress reactions within the neighbouring joints. Recommendations for the different indications are given. PMID- 2575859 TI - [A back rehabilitation school for patients with vertebral fractures]. AB - This paper describes the conception and the evaluation of a back school for patients with vertebral fractures. The school curriculum includes detailed information for the patient as well as physiotherapy, training in the proper way of performing the ordinary activities of the everyday-life, systematic self observation and relaxation training. From October 1987 until July 1989, 136 patients with vertebral fractures have completed the back school program. The effectiveness of the program was evaluated by a knowledge test and by an obstacle course. Both in the pre-post-confrontation as well as in the experimental group control group comparison we obtained significant differences in the goals. In conclusion, the present results imply that the described back school for patients with vertebral fractures is an efficient addition to conventional programs with physiotherapy only. PMID- 2575861 TI - [Data processing in trauma surgery. Experiences with the optical mark reader assisted data processing system Askitron MTF]. AB - Complications of recently used coding systems, error sensitivity and limited reliability of results of data in daily use still do not match with the benefit of data processing in trauma surgery. The relevant advantages of an optical mark reader based data processing system are presented. PMID- 2575860 TI - [Carbon fiber reinforced polysulfone implants for tumor surgery of the spine]. AB - Anterior tumor removal, cord decompression and spinal stabilization gain in significance in surgical treatment of vertebral tumors. An implant system, consisting of a basket as vertebral body replacement, plates and screws, was developed using carbon fibre reinforced polysulfone. This system allows to perform individually shaped, stable and short-distance spine fusions from an anterior approach. Moreover its radiolucence facilitates postoperative care and irradiation. Operative technique and clinical experience are demonstrated in two patients. PMID- 2575862 TI - [Facilitating the repositioning maneuver especially of the femur with external fixation. Temporarily attached "grips" in a 3-tube modular technic with a general orthopedic tube system]. PMID- 2575863 TI - In vitro development of metacyclic Trypanosoma simiae derived from bloodstream trypomastigotes. AB - A stock of Trypanosoma simiae was transformed into procyclic forms at 26 C in a semi-defined maintenance medium. After transformation, the trypanosomes were maintained in a modified Eagle's MEM medium. On day 35 of cultivation, epimastigotes attached to the bottom of the culture flask. From day 44 onwards, metacyclic-like trypanosomes were observed. Subcutaneous injections into pigs of trypanosome suspensions obtained from cultures on day 10 were not infective, whereas culture-derived metacyclics (days 44, 63 and 69) were highly pathogenic. PMID- 2575864 TI - Occupational exposure to hepatitis B virus in hospital personnel in Cairo, Egypt. AB - To identify hospital occupational categories at potential risk of hepatitis B virus infection, a serologic survey was conducted for hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) by enzyme-linked immunosorbent assay in 765 employees at 4 hospitals in Cairo, Egypt. Overall, 3% HBsAg and 28% anti-HBs seromarkers. Combined HBsAg and anti-HBs frequencies by occupational group were: nonprofessional staff (60%), dentists (32%), graduate nurses (33%), physicians (29%), and student nurses (26%). The main risk factors for hepatitis B infection were frequency of exposure to patients' blood (for physicians, p less than 0.001) and to patients with jaundice (for dentists, p less than 0.01), and years of exposure to patients, as reflected by duration of occupation (for physicians, p less than 0.001) and by age of health care worker. Seropositivity by sex was greater for males (p less than 0.01). Physician specialties with highest risk of infection (29 to 53%) were surgery, infectious diseases, obstetrics-gynecology, and emergency medicine. PMID- 2575865 TI - Binding of lectin-gold conjugates by two Trypanosoma cruzi strains in ampullae and rectum of Triatoma infestans. AB - The ampullae and recta of Triatoma infestans infected with Trypanosoma cruzi were incubated with lectin-gold conjugates of wheat germ agglutinin (WGA) and soy bean agglutinin (SBA) and investigated by electron microscopy. T. cruzi colonized the whole lumen of the ampullae. The rectal pads with their intensive intracellular membrane system and thin cuticle were often covered by a compact layer of flagellates, whereas the remaining rectal sac- recognizable by a thick layered cuticle - was colonized less densely. All freely accessible stages of T. cruzi strain 'Chile 5' (Zymodeme 1) showed a reaction with SBA-gold complexes but not with WGA, revealing that N-acetyl-galactosamine and/or galactose but no N-acetyl glucosamine residues were present on the surface. T. cruzi strain 'Chile 7' (Zymodeme 2) also reacted with SBA. WGA-bovine serum albumin-gold conjugates bound strongly to the surface of epimastigotes of this strain, in variable amounts to stages in transition to trypomastigotes, but not to metacyclic trypomastigotes. PMID- 2575866 TI - The use of Phytolacca dodecandra berries in the control of trematode-transmitting snails in Zimbabwe. AB - Phytolacca dodecandra, a plant with berries of a known molluscicidal potency, was cultivated in Chiweshe. Studies on the snail population density of Bulinus globosus and Lymnaea natalensis as well as schistosome infection rates in the former were carried out in two streams, in one of which a water extract of P. dodecandra berries was applied in late April and May 1987. Snail sampling was carried out twice a month from April 1986 to April 1988, that is for 12 months prior to and after the mollusciciding exercise. B. globosus snails obtained from both streams were examined for infection by cercarial shedding before they were returned to their sites of collection. The 8-h water extract of P. dodecandra was applied to human watercontact points. The two applications were aimed at achieving a concentration of 50 mg/l. No snails were recovered from the experimental sites for a period of 7 months after the mollusciciding exercise. Snails were recovered in the treated sites only after the onset of the rainy season. PMID- 2575867 TI - 2,2'-Dicarbomethoxyamino-5,5'-dibenzimidazolyl ketone--a new antifilarial agent. AB - The activity of 2,2'-dicarbomethoxyamino-5,5'-dibenzimidazolyl ketone (II, C.D.R.I. Comp. 82/437) has been evaluated for its micro- and macro-filaricidal efficacy against Litomosoides carinii in rodents. A dose of 3 mg/kg (i.p.) and 50 mg/kg (oral) x 5 days of Comp. 82/437 was found to eliminate almost 100% of adult worms and microfilariae of L. carinii in cotton rat. It also killed 100% and 97% of adult worms and microfilariae of Dipetalonema viteae and Brugia malayi in Mastomys natalensis respectively, at 150 and 200 mg/kg x 5 days orally. The compound also exhibited marked chemoprophylactic and in vitro activity against L. carinii. PMID- 2575868 TI - Application of a biochemical key to study transmission of malaria and Bancroftian filariasis in sibling species of the Anopheles gambiae complex in north-eastern Tanzania. AB - A biochemical key was applied in order to study transmission of malaria and Bancroftian filariasis in Anopheles gambiae sensu stricto, An. arabiensis and An. merus in different localities in north-eastern Tanzania. The technique was found to be a useful additional taxonomic tool for field entomologists. Significant differences between species in the rate of infection with Bancroftian filariasis were obtained between An. gambiae s.s. and An. funestus (P less than 0.005) and between An. funestus and An. arabiensis (P less than 0.0001). There were also significant differences between most of the investigated localities in the rate of filarial infection. However, there were no significant differences between the three species or between localities with respect to malaria sporozoite rates. Possible reasons for the observed variation between species and localities with respect to vectorial activity for Bancroftian filariasis are discussed. PMID- 2575869 TI - Mediterranean spotted fever in Salamanca, Spain. Epidemiological study in patients and serosurvey in animals and healthy human population. AB - Mediterranean spotted fever is a spotted fever group rickettsiosis caused by Rickettsia conorii. The fever has a recognized incidence in large geographic areas, and its presence in Salamanca Province (Spain) has been well documented since 1981. This work presents the results of the centralized prospective survey carried out in this area and was designed to study the epidemiological behavior of the disease and the prevalence of antibodies against R. conorii among animals and healthy human population. In 110 patients with confirmed diagnosis by an immunofluorescent antibody test we have observed a bimodal temporal curve of incidence of Mediterranean spotted fever in our zone and their predominant origin in villages under 2000 inhabitants. The serosurvey in a statistically representative sample of the human population of Salamanca shows a rate of 73.5% of reactive sera and percentages as high as 82% in samples from small villages. The seroepidemiological study of 300 animals reveals a widespread response to rickettsial antigens throughout the province. Immunofluorescent antibody titers of greater than or equal to 1:40 are present in 93% of dogs and high rates and titers are detected in other domestic mammals, suggesting their feasible epidemiological role in Mediterranean spotted fever. PMID- 2575870 TI - Immunological alterations in uncomplicated Plasmodium falciparum malaria. Relationship between parasitaemia and indicators of macrophage activation. AB - Numerical alterations of circulating lymphocytes were investigated in 37 Brazilian patients with uncomplicated Plasmodium falciparum malaria and in a group of 15 healthy controls. The number of CD4+ T helper/inducer cells was significantly lower in patients than controls, whereas absolute numbers of CD8+ suppressor/cytotoxic T cells did not differ between the groups. TNF and neopterin levels were markedly increased in the plasma of patients and remained slightly elevated after chemotherapy with clindamycin. Neopterin, but not TNF levels, were significantly correlated with parasitaemia. TNF was inversely related to monocyte counts. Interferon gamma could not be detected in the plasma of control subjects and was observed in only one patient. We conclude that in uncomplicated falciparum malaria the distribution of phenotypes of circulating lymphocytes are altered slightly and that the high plasma levels of TNF and neopterin indicate excessive release of these molecules by activated macrophages and the activation of cellular immune mechanisms during the infection. PMID- 2575871 TI - In vitro drug sensitivity test for Trypanosoma brucei subgroup bloodstream trypomastigotes. AB - An in vitro test has been developed to determine drug sensitivities of bloodstream trypomastigotes of Trypanosoma (T.) brucei isolates. The incorporation of [14C]leucine, [3H]thymidine and [3H]hypoxanthine into bloodstream forms in vitro was compared and different sensitivity test procedures with trypanocidal drugs were evaluated. Bloodstream forms were added to a microtiter plate with serial dilutions of trypanocidal drugs containing a cell free culture medium supplemented with a mammalian serum, which allows continuous cultivation of the bloodstream stages. After a preincubation period of 16 h, [3H]hypoxanthine was added, and after another 8 h, the cells were harvested with a cell harvester. The glass fiber filters on which the cells were collected were counted in a liquid scintillation counter and the percent inhibition determined as percentage of the control counts. This method gave accurate, reproducible results for T. (T.) brucei isolates tested with the trypanocidal drugs suramin, berenil, samorin, lomidine and Mel W. PMID- 2575873 TI - [XII World Congress of Obstetricians and Gynecologists]. PMID- 2575872 TI - In vitro drug sensitivity of Trypanosoma gambiense isolates. AB - Drug sensitivities of seven Trypanosoma b. gambiense isolates from patients in the Ivory Coast were measured for Mel B, suramin and lomidine using an in vitro incorporation test. Bloodstream forms were isolated from Mastomys natalensis, incubated in serial drug dilutions in a microtiter plate, after 24 h, radiolabeled hypoxanthine was added, and the plate incubated for another 15 h. Trypanosomes were then harvested onto glass fiber filters with a cell harvester and incorporation of label was determined in a liquid scintillation counter. From the incorporation inhibition curves IC50 and IC75 values were calculated. IC50 values for Mel B ranged from 0.5 to 4.6 ng/ml, for suramin from 7.2 to 30.5 micrograms/ml, and for lomidine from 2.1 to 7.0 ng/ml. Isolate TH-1/78E(031) was the least sensitive to all three drugs while TH-1/78E(020), TH-64/78E(020) and TH 31/78E(025) were the most sensitive to the drugs used. THDAL 1030R, an isolate from a patient who relapsed after three consecutive Mel B treatments, showed an IC50 value for Mel B of 1.20 ng/ml. The in vitro drug sensitivity test gave reproducible results for the T b. gambiense isolates tested. PMID- 2575874 TI - Bradycardia associated with vecuronium. PMID- 2575876 TI - Fluorescence diagnosis and photochemical treatment of diseased tissue using lasers: Part I. AB - Lasers are useful in many applications in medicine and biology. Historically, most laser use has involved heat generated in the interaction of the laser beam with the tissue. Today, however, the spectroscopic aspects of this laser use are playing a more dominant role in a number of applications. In this two-part series, Sune Svanberg and co-workers present illustrations of emerging clinical applications from cooperative work performed by the Lund Institute of Technology and the Lund University Hospital. Part I includes a survey of laser techniques for atomic and molecular analyses of samples of medical interest, spectroscopic analysis of the laser-induced plasma obtained when a high-power pulsed laser beam interacts with tissue, and the use of tumor-seeking agents in combination with laser radiation to provide new possibilities for malignant tumor detection and treatment. Part II, which will appear in the January 1, 1990, issue, describes the use of laser-induced fluorescence for tumor and plaque diagnostics. Different lasers have been used, and research efforts increasingly are being focused on excimer lasers and lasers in the IR region for the ablation of atherosclerotic plaques, cell layer by cell layer. PMID- 2575875 TI - [Sufentanil: the effect on cardiocirculatory parameters and intubation conditions on administration of pancuronium or vecuronium]. AB - A lack of uniform methodology used in the assessment of moderate doses of sufentanil in combination with non-depolarizing neuromuscular blocking drugs formed the basis of the current study which compared under randomized conditions the effects of sufentanil-pancuronium versus sufentanil-vecuronium on hemodynamics, intubating conditions and chest wall rigidity during induction of anesthesia. MATERIAL and METHODS. One hundred and twenty ASA physical status I and II patients aged between 20 and 40 years of age who were undergoing elective urological surgery were included in the study. Premedication consisted of 0.15 mg kg-1 diazepam, given orally 60 min prior to induction of anesthesia. Patients were randomly divided into eight groups of 15 each to receive 0.5 microgram kg-1 sufentanil or placebo in combination with pancuronium (groups I-IV) or vecuronium (groups V-VIII) Within each group, patients were randomly allocated to receive the relaxant either as a single bolus dose of 0.095 mg kg-1 pancuronium or 0.1 mg kg-1 vecuronium, or in divided doses (the priming principle), the smaller priming dose (0.015 mg kg-1 pancuronium or 0.015 mg kg-1 vecuronium) being administered 2 min before induction of anesthesia with 5 mg kg-1 thiopentone, followed by the second intubating dose of 0.080 mg kg-1 pancuronium or 0.085 mg kg-1 vecuronium. To maintain blind study conditions in the groups, the patients given the relaxants in one dose were given an equivalent volume of saline 2 min prior before 5 mg kg-1 thiopentone. Intubating was attempted 60 s after administration of the main dose of the relaxant, and conditions were assessed on a four-point scale: excellent, satisfactory, fair, or poor. Neuromuscular transmission was monitored with the Datex Relaxograph, a neuromuscular transmission analyzer, that utilizes the integration of the EMG response. Producing train-of-four (TOF) stimuli, with a pulse width of 100 microseconds and a frequency of 2 Hz every 20 s the following parameters were recorded by the Datex Relaxograph: The percentage of first twitch amplitude compared with the reference (T1), and the train-of-four (TOF) ratio, i.e., the ratio of last twitch height to first height. Measurements were taken after premedication in the operating room, the value which served as a baseline (t0), 1 min after sufentanil or placebo (t1), 1 min after priming or placebo (t2), 1 min after thiopentone (t3), and 1 min after intubation (t4).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2575877 TI - Determination of underivatised efaroxan and idazoxan in blood plasma by capillary gas chromatography with mass-selective detection. AB - Sensitive and specific methods for the determination of efaroxan and idazoxan in blood plasma have been developed based on solvent extraction, chromatographic separation and quantification by selected-ion monitoring using a quadruple mass selective detector. The use of a short non-polar bonded-phase capillary gas chromatography (GC) column facilitated rapid separation of the compounds of interest from internal standards, metabolites and endogenous material. Of equal significance was the ability to chromatograph these basic compounds without prior derivatisation. The application of bonded-phase capillary GC coupled to selected ion monitoring resulted in robust analytical procedures with sub-ng ml(-1) sensitivity and high selectivity. PMID- 2575878 TI - Effects of fenoldopam on cecal blood flow and mechanical activity in horses. AB - Lateral cecal arterial blood flow, carotid arterial pressure, heart rate, and mechanical activity in the duodenum, right ventral colon, cecal body, and cecal apex were measured in 6 conscious healthy horses for 60 minutes during and for 120 minutes after IV infusion of 0.9% NaCl solution (control) or fenoldopam. There were no significant changes in these measurements during or after infusion of 0.9% NaCl (saline) solution. Fenoldopam, a selective dopamine-1 receptor agonist, was administered in saline solution at dosages of 0.01, 0.05, and 0.1 micrograms/kg/min. Intravenous infusion of fenoldopam at 0.01 microgram/kg/min significantly increased heart rate, but did not change average carotid arterial pressure or lateral cecal arterial blood flow. Intravenous infusion of fenoldopam at both 0.05 and 0.1 microgram/kg/min significantly increased heart rate, significantly decreased average carotid arterial pressure, and significantly increased lateral cecal arterial blood flow. Intravenous infusion of fenoldopam at 0.01, 0.05, and 0.1 microgram/kg/min did not significantly change the mechanical activity measured by the area under the strain gauge deflection curve for the duodenum, right ventral colon, cecal body, or cecal apex. These results suggest that dopaminergic-1 receptors are present on the colonic vasculature of horses. There was no evidence, however, that dopaminergic-1 receptors exist on the visceral smooth muscle of the duodenum, right ventral colon, cecal body, or cecal apex of horses. PMID- 2575879 TI - [Fragile X syndrome: what do we know today?]. PMID- 2575880 TI - [Current facts on ulcer disease]. AB - In the second half of this century, some important changes characterized the peptic ulcer history. The overall incidence of ulcer disease markedly decreased, with some differences in the various geographic areas and according to socioeconomic development of population. Peptic ulcer seems now more frequent in women and in the elderly patients, in comparison with the past. The appearance of H2-Receptor Antagonists determined a decline of ulcer surgery, because the ulcer is become a medical disease. Pyloric stenosis also, after ten years of H2 Receptor Antagonists treatment, markedly decreased. Indeed, the problem of acute complications is still actual. The detailed analysis of patients hospitalized, shows significative decrease of acute complications in patients with chronic ulcer and a marked anamnestics. The efficacy of medical treatment in the control of acute ulcer complications, seems to be balanced with new etiopathogenetic factors, which are able to start the appearance of acute complications of the disease (increased assumption of ulcerogenic drugs; smoke and alcohol abuse; increased socio-politic engagement of women and improved resuscitations technics). PMID- 2575881 TI - [Retroperitoneal and mediastinal fibrosis complicating periarteritis nodosa]. PMID- 2575882 TI - [Ki-1 large cell lymphoma with secondary xanthomatous infiltration of the lesions by chemotherapy]. PMID- 2575883 TI - Motile aeromonas infection of striped (grey) mullet Mugil cephalus. AB - Infection of striped mullet (Mugil cephalus) with Aeromonas hydrophila results in an acute septicemic disease. The disease can be experimentally induced by intramuscular injection, skin or gill scarification or by the oral route using pellets purposely seeded with bacteria. The organism was isolated from the blood 1-2 days after infection and from all organs 24 hr or longer after infection. The disease is characterized by early inflammatory and proliferative changes and later necrotic changes. Enteritis and hepatic necrosis are constant findings in aeromonad disease of M. cephalus but surface lesions are not pathognomic for these infections in mullet. Death of infected fish may be attributed to bacterial toxins which cause necrosis of parenchymal organs and soft tissue structure. PMID- 2575884 TI - Observations on the seasonal incidence and diel oviposition periodicity of Haemagogus mosquitoes (Diptera: Culicidae) in Trinidad, W.I.: Part I. Haemagogus janthinomys Dyar. AB - The diel oviposition periodicity of sylvan Haemagogus janthinomys Dyar in the Pt. Gourde Forest, Trinidad, West Indies was monitored weekly for 53 weeks using conventional ovitraps. During the wet season (September to November 1981 and May to September 1982) a large well-defined unimodal peak occurred six to eight hours after sunrise (comprising 94% of eggs laid and 91% occurrences). During the dry season (December 1981 to May 1982), a small less-well-defined peak occurred two to four hours before sunset (comprising 6% of eggs laid). The combined data showed a diurnal oviposition pattern with eggs laid from noon to sunset. The numbers of eggs and of used ovitraps found during the wet season were significantly (P less than 0.001) higher than those found during the dry season. PMID- 2575886 TI - Study of the negative inotropic action of somatostatin. AB - Somatostatin was evaluated as a chronotropic and inotropic agent in isolated, spontaneously beating guinea-pig atria. Somatostatin (3 x 10(-5)-1 x 10(-3) mM) caused a concentration-dependent negative inotropic effect and a small reduction of atrial rate. The negative inotropic effect of somatostatin was evaluated at different concentrations of extracellular calcium, on the positive inotropic response induced by calcium and on the positive chronotropic response induced by adrenaline. Small, nonsignificant changes in atria response to somatostatin were found both with the lowest (1.25 mM) and with the highest (5 mM) calcium concentration in the medium. Somatostatin (1 x 10(-4)-1 x 10(-3) mm) did not substantially modify the positive inotropic action of calcium; this substance (1 x 10(-3 mM) caused a parallel shift to the right of the adrenaline concentration response curve. These results suggest that the negative inotropic and chronotropic actions of somatostatin do not appear to be due to an action on the voltage-sensitive calcium channels, but rather to an action on the calcium channels excited by the stimulation of beta-receptors, whose function is probably cooperative with that of the voltage-sensitive channels. PMID- 2575885 TI - Interaction of rilmenidine and clonidine with pre- and postjunctional alpha adrenoceptors in rat and rabbit blood vessels and in rat kidneys. AB - In several blood vessels, the influence of the alpha 2-adrenoceptor agonists rilmenidine and clonidine was compared. In aortas of rat and rabbit and in the rabbit pulmonary artery, both compounds evoked contractions due to stimulation of postjunctional alpha 1-adrenoceptors. In the aorta of the rat, but not in that of the rabbit, removal of the endothelium markedly enhanced the contractions to rilmenidine and clonidine. At the alpha 1-adrenoceptors, clonidine was about 135 times more potent than rilmenidine. The activity of both substances at post- and prejunctional alpha 2-adrenoceptors was compared in the rabbit saphenous vein. Rilmenidine and clonidine evoked contractions of the vein by stimulating postjunctional alpha 2-adrenoceptors and decreased the stimulation-induced overflow of [3H]-noradrenaline by activating the prejunctional alpha 2 adrenoceptors. At the post- and prejunctional alpha 2-adrenoceptors, clonidine was about 30 times more potent than rilmenidine. These data illustrate that, although less potent than clonidine, rilmenidine is 5 times more specific for the alpha 2-adrenoceptors. In the isolated perfused rat kidney, rilmenidine and clonidine antagonized the vasoconstrictions induced by noradrenaline. Although the exact mechanism of this inhibitory response remains to be elucidated, our results indicate that rilmenidine may possess some interesting properties at the level of the renal circulation. PMID- 2575887 TI - Positive chronotropic and inotropic effects of pimobendan (UD-CG 115 BS) in isolated, cross-circulated canine heart preparations. AB - The effects of pimobendan on the sinus node pacemaker activity and atrial contractility and on the left ventricular contractility were investigated in the isolated, cross-circulated right atrial and left ventricular preparations of the dog. Pimobendan, at a dose range of 1 to 1,000 nmol, injected into the sinus node artery of the isolated atrium, induced dose-dependent positive inotropic and chronotropic responses. At the same doses, it also induced dose-dependent increases in the left ventricular contractile force, similar to those in the atrial one, although the norepinephrine (NE)- and isoproterenol-induced positive inotropic effects in the ventricles were less than those in the atria. The positive cardiac effects were not inhibited by propranolol but they were depressed by intramural vagal nerve stimulation. These results suggest that pimobendan increases left ventricular contractility more effectively than atrial contractility in comparison with a beta-adrenoceptor agonist and that the positive cardiac effects of pimobendan were partially induced by a phosphodiesterase inhibition but not by a beta-adrenoceptor activation in the dog heart. When pimobendan, at a dose of 10 to 1,000 micrograms/kg, was cumulatively administered into the jugular vein of the support dog, a decrease in arterial blood pressure and an increase in heart rate were dose-dependently observed in the support dog. Half a minute after administration, the positive inotropic and chronotropic responses were induced in the isolated atrium in a dose-related manner. The pimobendan-induced positive cardiac effects were not inhibited by i.v. administration of propranolol, whereas the isosorbide dinitrate-induced positive chronotropic effects were significantly inhibited. These results indicate that pimobendan directly increases cardiac contractility and heart rate with vasodilatation in anesthetized dogs. PMID- 2575888 TI - Benzodiazepines facilitate the stimulatory action of gamma-aminobutyric acid (GABA) on basal and veratridine-evoked catecholamine release from cultured bovine adrenal chromaffin cells. AB - Effects of benzodiazepines were investigated on the gamma-aminobutyric acid induced modulation of the basal and veratridine-evoked catecholamine release from cultured bovine adrenal chromaffin cells. GABA by itself, caused catecholamine release and facilitated veratridine-evoked catecholamine release. Midazolam enhanced the GABA-evoked catecholamine release in a dose-related fashion and further facilitated the enhancement by GABA of the veratridine-evoked catecholamine release. Clonazepam, a selective central-type benzodiazepine receptor agonist, also enhanced the GABA-induced catecholamine release, whereas ethyl-beta-carboline-3-carboxylate, an inverse agonist of the benzodiazepine receptor, reduced the GABA-evoked catecholamine release. The dose-response curve of the GABA-evoked catecholamine release was shifted to the left by midazolam without affecting the maximal response to GABA. Facilitation by midazolam and clonazepam of the GABA action or inhibition by ethyl-beta-carboline-3-carboxylate was antagonized by RO15-1788, which by itself had no effect on the basal or GABA- and veratridine-evoked catecholamine release. These results suggest that the central-type benzodiazepine receptor participates in the GABAergic modulation of the catecholamine release from adrenal chromaffin cells. PMID- 2575889 TI - Beta-adrenoceptor agonists do not reduce hydrogen peroxide production from superoxide radicals. AB - Recently, it has been reported that beta-adrenoceptor agonists containing a catechol moiety, reduce hydrogen peroxide production by alveolar macrophages, an effect suggested to be due to scavenging by the catecholamines of superoxide, the precursor of hydrogen peroxide. However, catecholamines interfere with the method used, in that study, to determine hydrogen peroxide formation. We re-examined the obtained results using two independent methods for measuring hydrogen peroxide that are not affected by catecholamines. We found that catecholamines, in a concentration up to 10(-5) M, had no effect on hydrogen peroxide formation out of superoxide. It was, furthermore, established that reduction of hydrogen peroxide formation by scavenging of superoxide by catecholamines is not very likely. PMID- 2575890 TI - Interactions of R(+) and S(-) isomers of befunolol, a partial agonist with high and low affinity sites of beta-adrenoceptors in guinea-pig taenia caecum. AB - The beta-adrenomimetic and beta-adrenolytic activities of R(+) and S(-) isomers of befunolol, a beta-adrenergic partial agonist, were studied in the guinea-pig taenia caecum. The pA2 value (9.38) of the S(-) isomer against S(-) isoprenaline was significantly different from that (7.94) of the R(+) isomer, while the pD2 values and intrinsic activities of R(+) and S(-) isomers were not significantly different from each other. The competitive inhibition curves of the specific binding of [3H]befunolol (50 nM) to the microsomal fraction from the guinea-pig taenia caecum by S(-) and R(+) isomers were biphasic, suggesting two different affinity binding sites. The affinity ratio of the R(+) isomer against the S(-) isomer to the high affinity site was 0.081 while the affinities of R(+) and S(-) isomers to the low affinity site were not significantly different from each other. The affinity ratio of the R(+) isomer against the S(-) isomer to the high affinity site resembled their potency ratio in beta-adrenergic blocking action. These findings suggest that beta-adrenoceptors contain two different affinity binding sites and that the high affinity binding site for isoprenaline is more stereoselective than the low affinity binding site. PMID- 2575891 TI - [Use of 2 internal mammary arteries in coronary bypass. Combination with a bypass using the gastroepiploic artery in 2 cases]. AB - Coronary revascularisation by bilateral internal mammary artery grafting was performed in 39 patients. The left internal mammary was anastomosed to the left anterior descending (N = 22), the left lateral (N = 12) or diagonal artery (N = 5). The right internal mammary was implanted on the right coronary (N = 17), the left anterior descending (N = 16), the left lateral (N = 3) or diagonal artery (N = 3). In two cases, the inferior myocardial segments were revascularised by grafting the gastroepiploic artery. Three patients died and one patient had signs of postoperative myocardial infarction. Respiratory complications, usually mild, occurred in 5 patients. Bilateral internal mammary artery grafting should be reserved for: 1) young patients, 2) those without usable leg veins (varicose veins, previous stripping or coronary bypass surgery). The gastroepiploic artery is a useful arterial graft for revascularizing regions of the heart inaccessible to the internal mammary arteries. PMID- 2575892 TI - Lymphocyte gamma-glutamyl transferase activity in Behcet's disease. AB - In this study the activity of a membrane-bound enzyme, gamma-glutamyl transferase GGT (gamma-glutamyl transpeptidase - GGTP), was investigated in the peripheral blood lymphocytes (PBL) from patients with Behcet's disease. Lymphocyte GGT activity in Behcet's disease was found to be significantly lower than that of control lymphocytes (p less than 0.01). This altered activity may be due to the abnormality in the membrane of lymphocytes of Behcet's disease patients. PMID- 2575894 TI - [A 2-component tumor of the breast with carcinoid syndrome]. AB - The structures of a well-differentiated apudoma were combined with the foci of colloid carcinoma in a mammary gland tumour described. Two types of cells with argyrophil grains are distinguished depending on the argyrophil grain size, localization in the tumour cell cytoplasm and the ability to react with hormonal antisera. The first type cells correspond to the true apudocytes and produce serotonin and beta-endorphine. The smallest silver granules imitate the endocrine granules in the cells of the second type. The peculiar feature of this observation is in its clinical manifestations typical for the carcinoid syndrome. PMID- 2575893 TI - Mechanism of urinary excretion of methylmercury in mice. AB - To elucidate the mechanisms by which methyl-mercury (MeHg) is eliminated from organisms, male C57BL/6N mice were orally administered with MeHg chloride (5 mg/kg) and the chemical forms of its metabolites in plasma, urine and kidney were determined by column chromatographic analysis. Orally administered MeHg rapidly entered the circulation, accumulated in the kidney and other tissues, and was slowly excreted in the urine. Ultrafiltration and gel filtration analysis revealed that most of plasma MeHg was accounted for by its albumin conjugate. Cell fractionation analysis revealed that about 80% of renal MeHg was recovered from the 15,000 g supernatant fraction of the kidney homogenate. If the kidney was homogenized in the presence of serine-borate complex, a potent inhibitor of gamma-glutamyltranspeptidase (gamma-GTP), about 50% of the MeHg in the supernatant fraction was recovered as its glutathione S-conjugate while the rest was bound to cytosolic protein(s). The major part of urinary MeHg was accounted for by its cysteine conjugate. However, urinary excretion of its glutathione conjugate increased significantly if animals were pretreated with acivicin, an affinity labeling reagent for gamma-GTP. These and other results suggested that MeHg bound to albumin accumulated in the kidney predominantly via some non filtrating peritubular mechanism, and localized in renal cytosolic compartment as its glutathione- and protein-bound forms. The glutathione S-conjugate of MeHg in the tubule cells might be transferred to the lumenal space, hydrolyzed to the cysteine S-conjugate, and then excreted in urine. These sequential events might constitute an important eliminatory pathway for a hazardous mercurial metabolite in mice. PMID- 2575895 TI - [Antiplatelet agents: specific agonist inhibitors]. PMID- 2575897 TI - Mitochondrial DNA polymorphism in native Philippine cattle based on restriction endonuclease cleavage patterns. AB - An analysis of patterns of cleavage of mtDNA by restriction endonucleases was performed for nine individuals from the Philippine population of native cattle. MtDNA polymorphisms were detected in the restriction patterns generated by the following six enzymes, BamHI, BglII, EcoRV, HindIII, PstI, and ScaI. The restriction patterns showing polymorphisms were distributed nonrandomly among the nine individuals examined from the Philippine population of native cattle, indicating the existence of two separate types of mtDNA. These two types of mtDNA are very different from each other, at the level of subspecies. Since the native Philippine cattle are considered to represent an admixture of European and Indian cattle, the two types of mtDNA must be derived from the mtDNAs of both varieties. The polymorphic sites in mtDNA have been located on a restriction map, and the nucleotide substitutions at some of the sites have also been estimated. PMID- 2575896 TI - Effects on infarct size of reperfusion and pretreatment with beta-blockade and calcium antagonists. AB - The "mass of tissue at risk" and the myocardial infarct developed was studied in dogs subjected to either 24-h occlusion of the left anterior descending coronary artery or 2-h occlusion followed by 22-h reperfusion. The "mass of tissue at risk" was defined under anaesthesia at the time of occlusion using the microsphere technique. Twenty-four hours later the hearts were removed, sliced transversely and stained with 2,3,5-triphenyltetrazolium chloride to define the infarcted tissue. All myocardial tissue was mapped and cut into small pieces for weighing and radioactive counting. Radioactivity was present in all tissue, including the infarct. In the centre of the infarct, counts remained low and then increased very rapidly with distance just beyond the edge. Tissue at risk from infarction was taken as that with less than 15% of the peak left ventricular (non ischaemic) counts. A linear relationship was found between the mass of the left ventricular infarct and the left ventricular "mass of tissue at risk". The effect of 22 hours reperfusion was examined by this method and expressed by a regression equation. There was a significant decrease in slope for the regression line of the reperfusion data, (p less than 0.05, analysis of covariance), indicating less infarcted tissue for each gram of underperfused tissue. None of the drug pretreatments explored had any effect on infarct size in the 24-h occlusion model. With reperfusion, propranolol and flunarizine diminished infarct size compared with reperfusion only (p less than 0.05 for reduced slope, the new slope being not significantly different from zero). The effect of diltiazem was not so marked. Thus infarct size can be reduced with pretreatment, as long as the myocardium is reperfused. PMID- 2575898 TI - Genetic and synteny mapping of parathyroid hormone and beta hemoglobin in cattle. AB - Parathyroid hormone and the beta hemoglobin gene cluster, which are closely linked on human chromosome 11p15, were localized to bovine syntenic group (U7) with the gene for catalase by the use of bovine x hamster hybrid somatic cells. Restriction fragment length polymorphisms (RFLPs) were followed through informative pedigrees to determine a linkage map distance of 15.6 +/- 5.4 cM between the parathyroid hormone and hemoglobin genes. Allelic frequencies of the DNA fragment were compared in a small sampling of cattle from five different breeds. PMID- 2575899 TI - Novel restriction fragment length polymorphism of the growth hormone gene in inbred rats. AB - A novel restriction fragment length polymorphism in inbred rats was detected by Southern blot analysis with rat growth hormone cDNA as a probe. Four alleles, characterized by PstI fragments of 1.2, 1.1, 0.9, and 0.7 kb, respectively, were detected in 27 strains examined. The same distribution of polymorphisms was observed on digestion of DNAs of these strains with three other enzymes, PvuII, HindIII, and BamHI. Moreover, the same differences in length of allelic restriction fragments were obtained with these restriction enzymes as with PstI. These findings suggested that the polymorphism was caused by insertion or deletion of variable DNA segments in the second intron of the growth hormone gene. Linkage analyses using backcross progeny provided no evidence for close linkage between the restriction fragment length polymorphism locus and 10 other loci examined. PMID- 2575900 TI - Purification and characterization of a cytosolic transglutaminase from a cultured human tumour-cell line. AB - Transglutaminases are a family of Ca2(+)-dependent enzymes that catalyse the formation of isopeptide bonds between the side chains of glutamine and lysine residues. The enzymes have been hypothesized to be involved in a wide range of cellular processes, including growth and differentiation and stabilization of the cytoskeleton. The human epidermal carcinoma-cell line, A431 cells, have relatively high amounts of a cytosolic transglutaminase activity that varies upon treatment of the cells with epidermal growth factor. We demonstrate here that this cytosolic activity has the biochemical and immunological properties of a tissue transglutaminase. We also report the purification of this enzyme to apparent homogeneity by a protocol which involves a novel affinity-elution step. Polyclonal antibodies to the transglutaminase were raised and used to identify the enzyme by Western blotting. The availability of purified transglutaminase and antitransglutaminase antibodies will permit further study of the role of this enzyme in the growth of this hormone-responsive human tumour-cell line. PMID- 2575902 TI - Basal activities of adenylate and guanylate cyclase in lymphocytes and platelets of alcoholics. AB - Basal activities of adenylate cyclase and guanylate cyclase were determined in lymphocytes and platelets of alcoholics with different severity of alcoholic withdrawal syndrome. Compared to controls, significant changes were found in the basal activities of adenylate and guanylate cyclase in all groups of patients. Adenylate cyclase activity in lymphocytes has a positive correlation to the severity of the clinical states. Although we found increased guanylate cyclase activities in lymphocytes and decreased activities in platelets compared to controls, similar values of activities were obtained in all groups of alcoholics independently of their clinical state. PMID- 2575901 TI - Benzoate stimulates glutamate release from perfused rat liver. AB - In isolated perfused rat liver, benzoate addition to the influent perfusate led to a dose-dependent, rapid and reversible stimulation of glutamate output from the liver. This was accompanied by a decrease in glutamate and 2-oxoglutarate tissue levels and a net K+ release from the liver; withdrawal of benzoate was followed by re-uptake of K+. Benzoate-induced glutamate efflux from the liver was not dependent on the concentration (0-1 mM) of ammonia (NH3 + NH4+) in the influent perfusate, but was significantly increased after inhibition of glutamine synthetase by methionine sulphoximine or during the metabolism of added glutamine (5 mM). Maximal rates of benzoate-stimulated glutamate efflux were 0.8-0.9 mumol/min per g, and the effect of benzoate was half-maximal (K0.5) at 0.8 mM. Similar Vmax. values of glutamate efflux were obtained with 4-methyl-2 oxopentanoate, ketomethionine (4-methylthio-2-oxobutyrate) and phenylpyruvate; their respective K0.5 values were 1.2 mM, 3.0 mM and 3.8 mM. Benzoate decreased hepatic net ammonia uptake and synthesis of both urea and glutamine from added NH4Cl. Accordingly, the benzoate-induced shift of detoxication from urea and glutamine synthesis to glutamate formation and release was accompanied by a decreased hepatic ammonia uptake. The data show that benzoate exerts profound effects on hepatic glutamate and ammonia metabolism, providing a new insight into benzoate action in the treatment of hyperammonaemic syndromes. PMID- 2575903 TI - Bradykinin action in the rat duodenum: Ca2(+)-dependent effects of bradykinin on the activity of particulate guanylate cyclase. AB - The nonapeptide bradykinin has been found to exert opposite effects on cGMP synthesis in a plasma membrane fraction from the rat duodenum. In the absence of exogenous Ca2+ BK increased the activity of the duodenal particulate guanylate cyclase which is decreased, in contrast, in a medium containing 1 mM exogenous Ca2+. In a Ca2(+)-free medium, on the other hand, both BK effects are completely prevented. The results suggest a presumable role of pGC in BK signal transmission in the rat duodenum with calcium ions as a mediator and/or essential cofactor. PMID- 2575904 TI - [A membrane-bound alanine aminopeptidase from Acinetobacter calcoaceticus. 1. Isolation and purification of the enzyme]. AB - The alanine aminopeptidase of Acinetobacter calcoaceticus was found to be bound to the inner membranes only. The enzyme was solubilized by Triton X-100 and purified approximately 480-fold by gel filtration and affinity chromatography on alanine methyl ketone-AH-Sepharose 4B. The purified alanine aminopeptidase has a molecular mass of 212 kDa, estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme selectively catalyses the hydrolysis of N-terminal alanine residues of peptides. The enzyme is inhibited by p-hydroxy mercuribenzoate, 1,10-phenanthroline, and puromycin, but was activated by CO2(+) ions. PMID- 2575905 TI - [A membrane-bound alanine aminopeptidase from Acinetobacter calcoaceticus. 2. Substrate specificity of the enzyme]. AB - The substrate specificity of the membrane-bound alanine aminopeptidase from Acinetobacter calcoaceticus was investigated with a series of substituted amides of alpha-amino acids. In contrast to mammalian AAP forms, the rate of hydrolysis of the AAP from Acinetobacter calcoaceticus is higher using 4-nitranilide than 2 naphthylamide substrates. The enzyme affinity is very high for alanine substrates and decreases in the series of the amide substituents, from methyl coumarylamides, 4-nitranilides, 4-methoxynaphthylamides to the 2-naphthylamides. The alanine aminopeptidase shows its highest affinity to Ala-MCA (Km = 77 mumol(s)/1). PMID- 2575907 TI - Transfer of metaclazepam and its metabolites into breast milk. AB - Ten young women took part in this study a few days after delivery (day 3 and day 5 post partum). Lactation had developed normally but the newborn infants were not breast-fed. The study was intended to investigate whether metaclazepam (Talis), a new 1,4-benzodiazepine, and some of its metabolites were present in breast milk. Levels were measured in the plasma and milk. The levels in the milk showed that metaclazepam, N-desmethylmetaclazepam and two of its metabolites with a lactam structure could be found in small amounts. Differences in metaclazepam and N desmethylmetaclazepam concentrations in the breast milk on days 3 and 5 post partum are discussed. PMID- 2575906 TI - Ketone body utilization in duodenum. Differential effect of fasting on lipogenesis from acetoacetate and 3-hydroxybutyrate. AB - The effect of fasting and refeeding on oxidation, lipogenesis and amino acid synthesis from ketone bodies has been studied in neonatal chick duodenal mucosa. Oxidation and amino acid synthesis were higher from acetoacetate and were stimulated by fasting from both 3-hydroxybutyrate and acetoacetate. On the contrary, lipogenesis was always higher from 3-hydroxybutyrate and fasting reduced lipogenesis rate from acetoacetate (by 66%) but not from 3 hydroxybutyrate. Results suggests the existence of a cytosolic fast-dependent acetoacetyl-CoA synthetase in chick duodenal mucosa which is involved in phospholipid synthesis. PMID- 2575908 TI - The significance of T suppressor cells in the development of autoimmunity. AB - Despite intensive research, autoimmune-disease pathogenesis is still an enigma, but in the past decade Ts-cell defects have assumed a central role in this pathogenesis. Ts-cell dysfunctions have been reported in numerous autoimmune diseases (e.g. SLE, autoimmune thyroid disease, myasthenia gravis) and in animal models of autoimmune diseases. Therefore, it is currently believed that Ts cells are responsible for maintaining self-tolerance and that perturbations in suppressor functions may initiate development of autoimmune diseases. Ts-cell abnormalities can result from LCTA production, intrinsic biochemical alterations, genetic susceptibility, or environmental factors. Since Ts-cells dysfunctions are believed to initiate autoimmunity, it may be possible to treat autoimmune diseases by correcting the suppressor defects, and indeed, preliminary trials in this direction are promising. PMID- 2575909 TI - Immunology of bacteria and parasites. PMID- 2575910 TI - Immunity to Schistosoma mansoni in vivo: contradiction or clarification? AB - In recent years controversy and contradiction have hindered the elucidation of the immune effector mechanisms that are most effective against Schistosoma mansoni - an essential goal for the development of an effective vaccine. However, recent in-vivo studies have clarified the relative contributions of such mechanisms to protection. Here, Dario Vignali and colleagues summarize current evidence that suggests that both antibody and CD4+ T cells, in cooperation with macrophages, are crucial for the development of an effective response. In addition, a model is presented that may account for some of the discrepancies observed and which could be used as a basis for future research. PMID- 2575911 TI - Potential mechanisms for the cytopathic properties of HIV. PMID- 2575912 TI - Prediction of progression to AIDS by analysis of CD4 lymphocyte counts in a haemophilic cohort. AB - Serial CD4 lymphocyte counts were recorded in 112 anti-HIV-positive haemophiliacs who were followed for up to 8 years after seroconversion. The patients remained at low risk of developing AIDS until their CD4 lymphocyte count fell to 0.25 X 10(9)/l. From this point, the risk increased as their count approached zero. Using this result and on the assumption (which is evaluated) that the underlying trend over time in CD4 lymphocyte counts is linear, the predicted rate of progression to AIDS was calculated for the cohort. It was estimated that 73% (95% confidence limits 60-86%) of the cohort will develop AIDS within 15 years of HIV seropositivity. During 8 years of follow-up, this cohort had shown similar rates of progression to AIDS to other cohorts--haemophilic and otherwise--suggesting that this estimate may well have general applicability. The method described could be used to plan the provision of health-care resources for groups of anti HIV-positive patients as it allows the number of new cases of AIDS to be predicted year by year, even when the patients' dates of seroconversion are unknown. PMID- 2575914 TI - Do negative symptoms respond to pharmacological treatment? PMID- 2575915 TI - Negative symptoms, tardive dyskinesia and depression in chronic schizophrenia. PMID- 2575913 TI - Severe clinical manifestations of primary HIV infection. AB - Three cases of oesophageal candidiasis in association with primary HIV infection are described. In each case the candidiasis was associated with a decreased number of circulating CD4+ cells and responded well to treatment with ketoconazole. Clinicians should be aware that severe opportunistic infections may develop during this stage of infection, presumably as a result of transient immunodeficiency. We argue that the definition of primary HIV infection should be extended to include severe opportunistic infections and neurologic presentations. PMID- 2575916 TI - Substitution of amino acids in helix F of bacteriorhodopsin: effects on the photochemical cycle. AB - The effects of amino acid substitutions in helix F of bacteriorhodopsin on the photocycle of this light-driven proton pump were studied. The photocycles of Ser 183----Ala and Glu-194----Gln mutants were qualitatively similar to that of wild type bacteriorhodopsin produced in Escherichia coli and bacteriorhodopsin from Halobacterium halobium. The substitution of a Phe for either Trp-182 or Trp-189 significantly reduced the fraction of photocycling bacteriorhodopsin. The amino acid substitutions Tyr-185----Phe and Ser-193----Ala substantially increased the lifetime of the photocycle without substantially increasing the lifetime of the M photocycle intermediate. Similar results were also obtained with the Pro-186--- Gly substitution. In contrast, replacing Pro-186 with the larger residue Leu inhibited the formation of the M photocycle intermediate. These results are consistent with a structural model of the retinal-binding pocket suggested by low temperature UV/visible and Fourier transform infrared difference spectroscopies that has Trp-182, Tyr-185, Pro-186, and Trp-189 forming part of the binding pocket. PMID- 2575917 TI - Substitution of membrane-embedded aspartic acids in bacteriorhodopsin causes specific changes in different steps of the photochemical cycle. AB - Millisecond photocycle kinetics were measured at room temperature for 13 site specific bacteriorhodopsin mutants in which single aspartic acid residues were replaced by asparagine, glutamic acid, or alanine. Replacement of aspartic acid residues expected to be within the membrane-embedded region of the protein (Asp 85, -96, -115, or -212) produced large alterations in the photocycle. Substitution of Asp-85 or Asp-212 by Asn altered or blocked formation of the M410 photointermediate. Substitution of these two residues by Glu decreased the amount of M410 formed. Substitutions of Asp-96 slowed the decay rate of the M410 photointermediate, and substitutions of Asp-115 slowed the decay rate of the O640 photointermediate. Corresponding substitutions of aspartic acid residues expected to be in cytoplasmic loop regions of the protein (Asp-36, -38, -102, or -104) resulted in little or no alteration of the photocycle. Our results indicate that the defects in proton pumping which we have previously observed upon substitution of Asp-85, Asp-96, Asp-115, and Asp-212 [Mogi, T., Stern, L. J., Marti, T., Chao, B. H., & Khorana, H. G. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 4148-4152] are closely coupled to alterations in the photocycle. The photocycle alterations observed in these mutants are discussed in relation to the functional roles of specific aspartic acid residues at different stages of the bacteriorhodopsin photocycle and the proton pumping mechanism. PMID- 2575919 TI - [Autograft of blood stem cells]. AB - Autologous blood stem cell transplantation (ABSCT) is a new technique which has been increasingly used in recent years. It is now well established that ABSCT can be performed as safely as autologous bone marrow transplantation (ABMT) when high numbers of hemopoietic precursors are infused. Multiple leukophoreses are performed during marrow regeneration following chemotherapy-induced aplasia. Hemopoietic recovery (predominantly the granulocytic series) is probably faster after ABSCT than after ABMT. Among other advantages there may be minimal contamination by residual tumor cells in buffy-coats; however, this has not been fully investigated. PMID- 2575918 TI - Spontaneous rupture of the internal elastic lamina in the rat: the manifestation of a genetically determined factor which may be linked to vascular fragility. AB - The spontaneous rupture of the internal elastic lamina (IEL) in various arteries occurs to different extents in different rat strains. We have quantified this phenomenon in the caudal and renal arteries and abdominal aorta in two normotensive inbred strains: the Brown Norway (BN) and Long Evans (LE) strains. At 5 weeks of age, BN rats of both sexes exhibited small numbers of interruptions in the IEL of the caudal artery, whereas LE rats did not. Postpubertal male and female BN rats presented large numbers of IEL interruptions in the caudal artery and significant numbers in the renal artery and abdominal aorta, whereas LE rats showed few in the caudal artery and none in the other arteries. Treatment with beta-aminopropionitrile (BAPN, an inhibitor of lysyl oxidase, the enzyme involved in the formation of cross-links in elastin and collagen) increased the formation of IEL ruptures in both strains in the caudal and renal artery and in the abdominal aorta in BN rats, but not in the abdominal aorta of LE rats. Apart from IEL ruptures, which were more prevalent in BN rats, no differences were observed in the ultrastructure of the aortic elastic fibers between the two strains, either in controls or in BAPN-treated rats. When male rats of both strains were made hypertensive by unilateral nephrectomy and administration of deoxycorticosterone and salt, mortality was more precocious in the BN strain although blood pressure was significantly higher in the BN strain at only one time point. The incidence of cerebrovascular hemorrhage was 48% in BN rats and 0% in LE rats. Hypertension increased the formation of ruptures in the IEL in some arteries - to a greater extent in the BN than in the LE rats. These results raise the possibility that the propensity to spontaneous rupture of the IEL, which is in part genetically determined, may reflect a latent form of vascular fragility which becomes significant in hypertension, resulting in poor survival and susceptibility to cerebrovascular accidents. PMID- 2575920 TI - [Personal experience in the study of thyroid autoimmunity and endocrine exophthalmos]. AB - Most of the thyroid disorders are considered as being autoimmune diseases. It is the case for autoimmune thyroiditis where various antibodies are found. In Graves' Basedow disease, one or several immunoglobulin(s) which stimulate(s) the thyroid were found. In simple goitre, autoimmune origin is probable. We have measured the presence of anti-alpha-galactosyl antibody in various thyroid disorders. An increase titre was observed in progressive Graves' ophthalmopathy, untreated Graves' disease, progressive simple goitres and in autoimmune thyroiditis. Therefore, we think that the measure of anti-alpha-galactosyl antibodies represents reproducible parameter in order to know if the thyroid disease is or not in progression. PMID- 2575921 TI - Patterns of benzodiazepine use in Great Britain as measured by a general population survey. AB - In a general population survey by Gallup in Great Britain of 4148 subjects, 7.7% had taken benzodiazepines within the last year (male:female ratio 106:212). Younger subjects tended to take anxiolytics for shorter periods compared with older subjects, who often took hypnotics chronically. This pattern was most marked among females. Dosage escalation, tolerance, high daily dose usage, and hoarding were not common. A substantial proportion of current users had experienced difficulty in stopping their medication. Withdrawal problems were associated with being older than 45 years and consuming benzodiazepines for over 12 months. This lends support to the idea of benzodiazepine dependency. However, the appropriateness of long-term therapy for chronic symptoms cannot be ruled out. PMID- 2575922 TI - Neuroleptic malignant syndrome and psychotic illness. AB - A typical case of NMS and its successful treatment with bromocriptine is described. The authors noticed an inverse relationship between the process of recovery from NMS and the pre-existing psychotic illness. PMID- 2575924 TI - [ Neuro-depressive properties of essential oil of lavender]. AB - Toxicity for albino rats is very low. In mice an anxiolytic effect is exhibited and the pentobarbital evokated sleeping time is increased in animals given essential oil, but this effect disappears if they are administrated during five days. PMID- 2575923 TI - [Immunohistochemical absence of adrenergic neurons in the dorsal part of the solitary tract nucleus in sudden infant death]. AB - The immunohistochemical distribution of TH and PNMT containing neuronal elements was investigated utilizing peroxidase anti-peroxidase methods in newborn control and sudden infant death syndrome (SIDS) brainstems. The TH immunoreactive neurons, within the medulla oblongata, displayed a similar distribution in both control and SIDS tissue. However, PNMT immunoreactive neurons seen in the dorsal part of the nucleus of tractus solitarius in control tissue were not observed in SIDS tissue. This alteration of adrenergic neurons in the dorsal part of NTS (region reported to be implicated in the control of blood pressure and respiration) could explain the cardiorespiratory disorders in SIDS. PMID- 2575925 TI - [Morphologic and enzymatic characteristics of healthy human kidney epithelial tubular cells in culture]. AB - The present study defines morphological and enzymatic characteristics of human healthy renal tubular cells in primary culture, and during three passages. The results confirm the ability to culture human renal tubular cells and to quantitatively evaluate the activity of specific tubular enzymes in the cells and in the culture medium. Such determinations can be compared to similar enzyme activity research in renal biopsies or in urines, to investigate human renal cell functions, in clinical, pharmacological or toxicological approaches. PMID- 2575926 TI - [A study of DNA fingerprinting in China]. AB - A recombinant DNA insert which could be hybridized with variable number of tandem repeat (VNTR) sequence probe was obtained from the screening of human genomic DNA library and it was cloned into plasmid for using as a probe designated as ph 296. Highly individual specific DNA fingerprints was produced by hybridizing radioactive labelled ph 296 with restriction endonuclease Hinf I digested genomic DNA of Chinese individuals of Han origin. The number of DNA fragments greater than or equal to 4 kb per individual was 13.6 +/- 3.0; the frequency of shared DNA fragments in unrelated random-paired individuals was 0.25; and the probability that all fragments were detected in both random-paired individuals was 2.0 x 10(-9). ph 296 is an locus-specific probe. The application of DNA fingerprinting is discussed. PMID- 2575927 TI - [Infection of human endothelial cells by the virus causing hemorrhagic fever with renal syndrome]. PMID- 2575928 TI - [Gene diagnosis of hemophilia A]. AB - Hemophilia A is the most common inherited bleeding disorder in man. The disease is caused by a deficiency in the gene for factor VIII. A genetic marker in the form of RFLP within or tightly linked to the factor VIII gene may serve as a tag for the hemophilia gene, thus allowing both accurate carrier detection and earlier prenatal diagnosis. Five RFLP (BclI/FVIII-e18, XbaI/FVIII-i22, BclI/St14, TaqI/St14 and BglII/DX13), which are related to hemophilia gene, were studied. The frequencies of allele of TaqI/St14 and BglII/DX13 in Chinese are obviously different from those in Caucasian. By the use of RFLP, 21 families with hemophilia A were analysed. The feasibility and strategy of gene diagnosis of hemophilia A by the use of RFLP are discussed. PMID- 2575929 TI - [Relation of c-Ha-ras point mutation to the prognosis and metastasis of gastric carcinoma]. AB - Mouse fibroblast cell line NIH 3T3 was transfected with oncogene c-Ha-ras containing mutation at the 12th codon, which was cloned from a gastric cancer cell line. After the transformants were injected subcutaneously into the nude mice, metastatic foci in the lung were found. The exogenous c-Ha-ras and its transcript were identified in the cells of the metastatic foci. This shows that the expression of the mutated c-Ha-ras is responsible for the acquisition of the metastatic phenotype for the cells. Furthermore, PCR-RFLP analysis was used to determine the point mutation of c-Ha-ras in gastric cancer. 11 of 27 fresh tissues and cell lines from gastric cancer were identified to contain the mutation at the 12th codon, and a correlation was found between the point mutation and metastasis to the distant organs and the survival time after surgical operation. PMID- 2575931 TI - Decreased gamma-aminobutyric acid (GABA) modulatory effect on rat vas deferens neurotransmission after chronic administration of imipramine. AB - 1. Chronic (10 mg/kg, i.p., once daily for 14 days) but not acute (10 mg/kg, i.p., 24 hr) administration of imipramine resulted in a decrease in both the responsiveness and the sensitivity of the contractions of the isolated rat vas deferens elicited by field stimulation to GABA and (-)-baclofen. 2. In contrast, clonidine and isoproterenol effects were not altered by either treatment. 3. This study shows for the first time that GABA action in the peripheral nervous system is altered by chronic treatment with antidepressants, possibly by inducing changes in a postreceptor element. PMID- 2575932 TI - [Sulfasalazine in the treatment of chronic juvenile arthritis]. AB - In 38 children with juvenile chronic arthritis the authors tested Sulphasalazine in an open clinical trial. The drug was administered for 26 weeks, 20-30 mg/kg/day. The action of the drug was followed up with regard to clinical (number of criteria of juvenile chronic arthritis, functional state, period of morning stiffness, number of affected joints painfulness of joints) and laboratory (red cell sedimentation rate, circulating immunocomplexes) indicators. A favourable effect (improvement of at least five of the above indicators) was recorded in 42.1% of the children. Undesirable effects were found in 11 children (30%) incl. six where they were the cause of discontinuation of treatment. All undesirable effects were reversible. The majority of them (exanthema, headache, leukopenia, microscopic haematuria) developed during the first 3-4 weeks of treatment. PMID- 2575930 TI - Coexisting peptides in hypothalamic neuroendocrine systems: some functional implications. AB - 1. Coexisting with oxytocin or vasopressin in the cell bodies and nerve terminals of the hypothalamic-neurohypophysial system are smaller amounts of other peptides. For a number of these "copeptides" there is strong evidence of corelease with the major magnocellular hormones. Guided by the location of their specific receptors we have studied the effects of three copeptides, dynorphin, cholecystokinin (CCK), and corticotropin releasing hormone (CRH), on the secretion of oxytocin and vasopressin from isolated rat neural lobe or neurointermediate lobe preparations in vitro. 2. Dynorphin is coreleased with vasopressin from neural lobe nerve terminals and acts on neural lobe kappa-opiate receptors to inhibit the electrically stimulated secretion of oxytocin. Naloxone augments oxytocin release from the neural lobe in a manner directly proportional to the amount of vasopressin (and presumably dynorphin) released. 3. Cholecystokinin, coreleased with oxytocin by neural lobe terminals, has been shown to have high-affinity receptors located in the NL and to stimulate secretion of both oxytocin and vasopressin. CCK's secretagogue effect was independent of electrical stimulation and extracellular Ca2+ and was blocked by an inhibitor of protein kinase C. 4. CRH, coreleased with OT from the neural lobe, has receptors in the intermediate lobe of the pituitary, but not in the neural lobe itself. CRH stimulates the secretion of oxytocin and vasopressin from combined neurointermediate lobes but not from isolated neural lobes. Intermediate lobe peptides, alpha and gamma melanocyte stimulating hormone, induced secretion of oxytocin and vasopressin from isolated neural lobes. Their effect was, like that of CCK, independent of electrical stimulation and extracellular Ca2+ and blocked by an inhibitor of protein kinase C. 5. Among the CRH-producing parvocellular neurons of the paraventricular nucleus, in the normal rat, approximately half also produce and store vasopressin. After removal of glucocorticoid influence by adrenalectomy, virtually all of the CRH neurons contain vasopressin. 6. The two subtypes of CRH neurosecretory cells found in the normal rat possess different topographical distributions in the paraventricular nucleus, suggesting the possibility of differential innervation. Stress selectively activates the vasopressin containing subpopulation of CRH neurons, indicating that there are separate channels of regulatory input controlling the two components of the parvocellular CRH neurosecretory system. PMID- 2575933 TI - [Usefulness of long-term follow-up of gastric ulcer: a case load contribution to the natural history of gastric ulcer in relation to treatment with H2 blockaders]. AB - Thorough long-term clinical, endoscopic and biopsy follow-up (from 6 months to greater than 8 years; mean follow-up: 3 years 3 months) of a group of 202 cases of apparently benign gastric ulcer has enabled us to evaluate the natural history of gastric ulcer in relation to medical therapy with H2-blockers and to patient compliance when using such drugs. The results confirm the efficacy of H2 antagonist therapy in gastric ulcer healing and in the prevention of relapse. Thorough follow-up, moreover, made it possible to keep surgical operations for non-neoplastic causes down to very low numbers, only 3 patients (1.5%) being operated on for haemorrhagic emergencies and 12 (6%) for non-response to therapy. PMID- 2575934 TI - Structure of the ornithine transcarbamylase (OTC) gene and DNA diagnosis of OTC deficiency. AB - Complementary and genomic DNA clones corresponding to human ornithine transcarbamylase (OTC) have been isolated and analyzed. Restriction fragment length polymorphisms (RFCPs) on OTC gene locus were analyzed in Japanese female population. Based on these data, a prenatal diagnosis of OTC deficiency was carried out in a risk family. A C-to-T substitution was found in exon 5 of OTC gene is an another female patient. PMID- 2575935 TI - Separation of hepatoma-associated gamma-glutamyltransferase isoenzyme on cellulose acetate media with Triton X-100 and concanavalin A. PMID- 2575936 TI - Enhancement of the activity of thyroid-stimulating antibodies by anti-human IgG antibodies in vitro. AB - In an attempt to determine whether or not anti-human IgG antibodies could influence the activity of thyroid-stimulating antibodies (TSAb), we investigated the effects of anti-human Fc antibody (anti-Fc antibody) and IgG from rheumatoid arthritis patients (RA-IgG) on TSAb activity using FRTL-5 cells. It was found that these anti-human IgG antibodies enhanced the TSAb activity in vitro. FRTL-5 cells were first incubated with Graves' disease IgG for 30 min at 37 degrees C, then washed and incubated in Hanks' balanced salt solution with anti-human IgG antibodies for 60 min at 4 degrees C, and then for a further 120 min at 37 degrees C. The level of cAMP accumulated in the medium was determined by RIA. Anti-Fc antibody significantly augmented the cAMP formation stimulated by 16 out of 24 Graves' IgGs, whereas anti-F(ab')2 antibody did not potentiate cAMP accumulation. Three of five RA-IgGs, which are usually defined as specific antibodies for the Fc fragment of human IgG, mimicked these stimulatory effects. Protein A also potentiated the cAMP formation stimulated by Graves' IgGs. Furthermore, there was a significant correlation between the TSAb titres of these Graves' IgGs and the potentiating effects of anti-Fc antibody (r = 0.495, P less than 0.05, n = 21). These results suggest that the interaction of TSH receptor antibody with anti-human IgG antibodies might modulate thyroid function in Graves' disease. PMID- 2575938 TI - Genetics of the German cockroach. PMID- 2575939 TI - Do glia contribute to behaviour? A neuromodulatory review. AB - 1. The links between behavioural state, gross electrophysiology and the activity of neurons and astrocytes are reviewed to stimulate interest in the contributions that glia make to behaviour. 2. Behavioural arousal in which neuronal responsivity ("sensitivity") is elevated is also associated with a sustained (0.5 10 sec) potential shift (SPS). 3. There is powerful and accumulating evidence that the SPS is primarily of glial origin. 4. In epilepsy neurons are hyperactive and there is a massive SPS during seizures. In seizure free periods, epileptic animals frequently have elevated arousal responses and increased neuronal sensitivity, indicating that seizures may be due to elevation of the activity of a normally adaptive sensitizing mechanism. 5. The common finding of an astrocytic pathology in epilepsy and the links between arousal, neuronal sensitization, SPSs and seizures implicates a modulatory role for astrocytes in both health and disease. 6. Glia, especially astrocytes, may modulate neuronal responsiveness by regulation of the microenvironment. 7. At the current state of knowledge, regulation of extracellular ionic K+, Ca2+ and neurotransmitter glutamate and GABA seem to be the most important candidates for modulating neuronal sensitivity in arousal and abnormally for seizure genesis. 8. Both in phylogeny and in ontogeny, glia and neurons have intimate associations. 9. The functional astrocytic syncitium is in a prime position to control the ecology of neuronal populations and thereby their activity. 10. The physiology and biochemistry of glia-neuronal interactions offers exciting new prospects for developments in behavioural neuroscience. PMID- 2575937 TI - New perspectives on left ventricular hypertrophy: anatomy, physiology, and significance. AB - The advent of echocardiography has added an important and sensitive tool for assessment of left ventricular hypertrophy (increased left ventricular mass). Recent echocardiographic studies in large population-based samples suggest an epidemic of left ventricular hypertrophy. Preliminary data suggesting important prognostic importance for such left ventricular hypertrophy (independent of standard risk factors) has fueled interest in the development, determinants, and other features of the hypertrophy. Hemodynamic and neurohumoral factors are the most prominent stimuli to adaptive (physiologic) myocardial hypertrophy, which can progress to maladaptive (pathologic) hypertrophy. The overall blood pressure experience, overweight, the cardiovascular response to recurrent psychosocial stress and physical activity level are four important correlates and potential determinants of left ventricular mass in various urban-suburban populations. Determination of the relative contributions and interrelations of these and other factors (such as heredity) to various forms of left ventricular hypertrophy found in various demographic groups warrants intensive investigation. PMID- 2575940 TI - Vitamin C amelioration of the adrenal stress response in broiler chickens being prepared for slaughter. AB - 1. At 32 hr prior to slaughter, broiler chickens were treated for 24 hr with either: 1200 ppm of L-ascorbic acid (AA; Vitamin C) in their drinking water or with no-AA supplementation (controls; simultaneously maintained on tap water). 2. Following the dietary treatments, birds were stressed by cooping/starvation for 8 hr before being hauled to an abattoir for processing. As indices of stress status, blood corticosterone (B) levels and heterophil/lymphocyte (H/L) ratios were determined at 32 and 8 hr prior to slaughter, and immediately before slaughter (0 hr). 3. The results indicated that AA supplementation reduces the stress response (i.e. elevated plasma B levels and H/L ratios) evident in broiler chickens being prepared for processing. PMID- 2575941 TI - Renin release responses to in vitro prostaglandin challenge in the summer-active ground squirrel, Spermophilus lateralis. AB - 1. Using a renal cortical slice preparation from the summer-active ground squirrel, Spermophilus lateralis, resting renin release (RR) and tissue cyclic AMP content (TcAMPC) levels were found to be significantly higher and lower, respectively, than those previously reported for its hibernating counterpart. 2. At a 10(-5) M dose, PGE2 but not PGE1, PGF2-alpha or PGA1, significantly stimulated RR in the summer-active ground squirrel (SAGS). 3. Addition of agents which normally increase TcAMPC significantly potentiated the effect of PGE1, while preventing that of PGE2, on RR and TcAMPC. 4. Opposite TcAMPC changes may mediate the in vitro RR responses to PGE1 and PGE2 administration in the SAGS. PMID- 2575942 TI - Non-cutaneous peripheral thermosensitivity in the goat (Capra hircus). AB - 1. A 0.2 m2 area of the trunk skin was denervated and its center was externally cooled or warmed, when central body temperature was lowered. 2. When the denervated skin was cooled, the central body temperature, at which shivering occurred, was significantly higher than with warming of the denervated skin. 3. It is concluded that the difference was caused by temperature signals originating from thermoreceptors in tissue layers underneath the denervated skin. PMID- 2575943 TI - Allometry of resting metabolic rate in cockroaches. AB - 1. Resting VO2 at 22.7 degrees C was 0.217 +/- 0.007 ml O2/g/hr in Nauphoeta cinerea of 0.51 +/- 0.008 g body mass. 2. Whole animal resting metabolic rate for 11 cockroach species scaled allometrically: VO2 = 0.261 M0.776. 3. Allometry of resting VO2 among cockroach species is similar to that in vertebrates, and is consistent with models based on both "elastic similarity" and "biological similitude." PMID- 2575944 TI - Ionic basis of salt-induced receptor potential in frog taste cells. AB - 1. The ionic basis of the receptor potential elicited by salt stimuli in a frog taste cell was studied with intracellular microelectrodes and lingual artery perfusion. 2. The amplitudes of the receptor potentials induced by salts were decreased by 32-60% when interstitial Na+ and Ca2+ were replaced with choline+, tetramethylammonium+ and tetraethyl-ammonium+. 3. After removal of Na+ and Ca2+ from both interstitial and superficial fluids, the reversal potentials of NaCl induced receptor potentials changed depending upon the stimulus concentrations. 4. These results indicate that the direct influx of Na+ across the receptor membrane, as well as the influx of interstitial Na+ across the basolateral membrane, occurs during NaCl stimulation. PMID- 2575945 TI - The effects of norepinephrine and nutritional status on resting metabolic rates in the LA/N-cp rat. AB - 1. The effects of diet and norepinephrine (NE) on resting metabolic rate (RMR) were determined using indirect calorimetry in 6-month-old lean and corpulent LA/N cp rats. RMRs of lean rats were greater than the corpulent. 2. Ingestion of carbohydrate (CHO) in the unfasted and fasted states increased the RMR of both groups, especially in the lean phenotype when compared to oil. 3. Serum T3 and glucose concentrations were similar in both phenotypes. 4. The effects of NE on RMR were maximal after a 200 micrograms NE/kg body weight injections. PMID- 2575946 TI - Sugar best single chorda tympani nerve fiber responses to various sugar stimuli in rat and hamster. AB - 1. Sugar best single chorda tympani nerve fiber of rat and hamster were tested with six sugars. 2. Fibers were selected for this experiment, only if they responded to 1.0 M sucrose or 1.0 M maltose and they responded poorly to 0.1 M NaCl. 3. In rat, some single fibers gave larger responses to maltose than to sucrose, while in hamster nearly all nerve fibers responded best to sucrose. 4. The order of effectiveness of sugars was maltose greater than fructose greater than or equal to lactose greater than sucrose greater than glucose greater than galactose in rat and sucrose greater than fructose greater than or equal to glucose greater than or equal to galactose greater than maltose greater than lactose in hamster. PMID- 2575948 TI - The effects of increased dietary cellulose on the anatomy, physiology and behaviour of captive water voles, Arvicola terrestris (L.) (Rodentia: Microtinae). AB - 1. Wild water voles and captives on high fibre diets had significantly longer and heavier digestive tracts (especially the caecum) than captives fed a low fibre diet. 2. Increasing dietary cellulose increased food intake, faecal output and metabolic rate, and decreased digestibility. Some but not all added cellulose was digested. 3. The passage of food through the digestive tract was significantly faster on the diet with added cellulose. 4. Coprophagy included eating directly from the anus and eating faecal pellets from the floor of the cage. The frequency of the latter type increased significantly for animals on a high fibre diet. PMID- 2575947 TI - How do avian embryos breathe? Oxygen transport in the blood of early chick embryos. AB - 1. Chick embryos with primary circulation, up to about 3 days of development, show no hemoglobin-mediated transport of oxygen. 2. In embryos with secondary circulation, between 3 and 6 days of incubation, the vascular area acts as the respiratory organ. Its efficiency in the oxygen uptake is less than that of the chorioallantois of later embryos. On the contrary, oxygen release to the tissues is highly efficient. 3. A full efficient hematic uptake of oxygen is reached at about the 6th incubation day, when chorioallantois acts as the embryonic respiratory organ. 4. The different respiratory mechanisms of developing chick embryo are closely related to the functional properties of the various hemoglobins which are produced during the embryonic life. PMID- 2575949 TI - Reticulo-ruminal motility in cattle (Bos indicus) and water buffaloes (Bubalus bubalis) fed a low quality roughage diet. AB - 1. The effect of A and B sequence contractions of the reticulo-rumen on passage rate of digesta was compared in buffaloes and cattle fed low quality rhodes grass. 2. Both species ate the same amount per unit body weight but buffaloes spent 53% more time ruminating than cattle. 3. Buffaloes had fewer A and B sequence contractions each day and the rate of these contractions during eating, ruminating and at rest were slower. 4. A larger pool of fine feed particles in the rumen of buffaloes, generated by extra ruminating activity was associated with the 30% shorter mean residence time of particulate matter in the forestomach compared with cattle. 5. It is concluded that the difference in the number and frequency of contractions between the species was insufficient to affect passage rate of digesta from the stomach. PMID- 2575950 TI - Comparative milk composition of the bottlenosed dolphin (Tursiops truncatus), humpback dolphin (Sousa plumbea) and common dolphin (Delphinus delphis) from southern African waters. AB - 1. Gross compositional data for milk samples of Tursiops truncatus, Sousa plumbea and Delphinus delphis are presented and compared with existing cetacean milk values. 2. Two factors appear to govern fat content and calorific value of the milk: (a) habitat, and (b) the stage of lactation. 3. Delphinus milk is unusual in that it has a higher P than Ca content. 4. The Fe content in cetacean milk is higher than that for terrestrial mammals and may be related to improved O2 binding requirements. PMID- 2575951 TI - Altitudinal distribution and blood values in the toad, Bufo spinulosus Wiegmann. AB - 1. Red blood cell (RBC) count, RBC size, hematocrit, cell and blood hemoglobin concentrations and plasma total solid concentration were measured in 16 lowland (from near sea level up to 2700 m) and 18 highland (3200 up to close to 4500 m) adult toads (Bufo spinulosus). 2. Lowland toads showed higher hematocrit values than highland toads, but their blood hemoglobin concentration and plasma solid concentration were not significantly different. 3. Highland toads had smaller RBC size, higher corpuscular hemoglobin concentration, a trend toward larger RBC count and a considerably smaller body size. These features may contribute to their successful life at high altitude. PMID- 2575952 TI - Amiloride does not block taste transduction in the mouse (Slc:ICR). AB - 1. The receptor potential of the mouse taste cell was recorded with an intracellular microelectrode while taste stimuli were applied to the tongue surface of the anesthetized mouse. 2. A membrane depolarization accompanied by an increase in membrane resistance was observed after a sucrose stimulus. 3. A sodium-chloride stimulus initiated a membrane depolarization accompanied by a decrease in membrane resistance. 4. Amiloride elicits a depolarization of the membrane and is accompanied by an increase in membrane resistance. 5. Pre adapting the tongue to amiloride, which is known as a potent sodium channel blocker, did not alter the responses to sodium-chloride and other taste stimuli. PMID- 2575953 TI - A model for the oxygen-paradox in mouse cardiac muscle. AB - 1. Mouse ventricle strips provide a good model system for studying cellular damage in mammalian cardiac muscle. 2. Anoxia rapidly causes destruction of the myofilament apparatus that is characteristic of calcium-triggered damage in muscle cells, and it is suggested that anoxia promotes release of calcium from the mitochondria. 3. Oxygen exacerbates this damage which is independent of extracellular calcium; it is suggested that it initiates myofilament damage by activation at an intracellular site, probably the sarcoplasmic reticulum. PMID- 2575954 TI - Long-term heat adaptation results in an enhanced efficiency of muscarinically induced water secretion in rat submaxillary glands. AB - 1. Carbamylcholine-induced 86Rb+ and 36Cl- efflux, as markers of calcium mobilization and water secretion, respectively, were studied during 30 days of heat acclimation (at 34 degrees C) in rat submaxillary gland slices using perifusion techniques. 2. The fractional rate of 36Cl- efflux was markedly elevated with acclimation, reaching its maximal level on day 30, while that of 86Rb+, after an initial rise, returned to non-acclimated control levels. The total carbamylcholine-induced efflux of both ions markedly increased throughout the 30 days' acclimation. 3. The rapid increase in ion fluxes was accompanied by a transient increase in Na+ concentrations in the gland and a decrease in the saliva. 4. The data suggest that the acclimation-induced increase in secretory capacity is bi-phasic: initially, a rapid transient rise in ion fluxes accompanies a transient rise in muscarinic receptor density (Kloog et al., 1985). 5. Long term acclimation is characterized by increased efficiency of the cellular secretory mechanism(s), as demonstrated by the chronically increased efflux of ions. PMID- 2575955 TI - Effect of 3-methylindole on the plasma and lung concentrations of prostaglandins and thromboxane B2 in goats. AB - 1. The role of prostanoids in 3-methylindole (3MI)-induced lung disease was investigated. Goats were infused with 3MI in propylene glycol at a dose of 35 mg 3MI/kg body weight. Control goats were infused with propylene glycol alone. 2. Blood was collected at regular intervals starting 24 hr before and ending 72 hr following 3MI infusion. In a second experiment, 3MI-treated goats were killed at 2, 6, 12, 24, 48 and 72 hr post-infusion. The concentrations of PGF2 alpha, PGE, 6-keto PGF1 alpha and TXB2 in plasma and lung of 3MI-infused and control goats were determined by radioimmunoassay. 3. Comparison of individual prostanoid concentrations showed that 3MI-infused and control goats exhibited similar plasma profiles for all four prostanoids measured. 4. In addition, prostanoid concentrations in lungs did not seem to be affected by 3MI infusion. 5. Thus, plasma and lung prostaglandin and TXB2 concentrations do not appear to be altered in 3MI-induced lung disease. PMID- 2575956 TI - Effect of fasting and acute heat stress on body temperature, blood acid-base and electrolyte status in chickens. AB - 1. The tolerance of chickens to acute heat stress, evaluated by the time required to reach the critical body temperature (Tr) of 44.5 degrees C, was markedly enhanced as the period of fasting was extended. 2. Fasting reduced the rates of heat-induced changes in blood acid-base and electrolyte status. 3. Changes in Tr were correlated with changes in blood pH, pCO2, [Cl-] and [Pi] but not with changes in [Na+] or [K+]. 4. Blood acid-base and electrolyte status were related to Tr rather than time of exposure to heat stress. PMID- 2575957 TI - Blood biochemistry values of sheep (Ovis aries ligeriensis). AB - 1. Analysis of biochemical parameters were carried out on material pooled from 30 female sheep (Ovis aries ligeriensis). 2. The values determined were for the common metabolites and enzymes utilized for specific studies in general metabolism (urea, glucose, cholesterol, lipids, bilirubin, uric acid, creatinine, alkaline phosphatase, GOT, GPT, LDH, LAP, CGT, CK and amylase). 3. Results of these studies were compared with values from normal human adults. 4. The differences obtained in human and sheep ranges can be explained by the different physiology of the two species. 5. This study gives values for the sheep as an experimental animal in biomedical research. PMID- 2575958 TI - The effects of macrophage-derived cytokines on lipid metabolism in chicken (Gallus domesticus) hepatocytes and adipocytes. AB - 1. The effects of avian and mammalian cytokines on avian lipid metabolism were compared using cultured chicken hepatocytes and adipocytes. 2. Conditioned medium from an endotoxin-stimulated chicken macrophage cell line was used as a source of chicken cytokines. Incubation of chicken adipocytes with conditioned medium greatly decreased their lipoprotein lipase activity. 3. Inhibition of lipoprotein lipase synthesis in similar experiments in mammals has been attributed to the effects of TNF-alpha and/or IL-1, but recombinant human TNF-alpha and IL-1 had no effect on lipoprotein lipase activity in chicken adipocytes. 4. Conditioned medium from chicken macrophages produced a 2-fold increase in lipogenesis in chicken adipocytes but had no effect on lipogenesis in chicken hepatocytes. 5. The results point to major differences between mammals and birds in the way that lipid metabolism responds to cytokines and provide further evidence that mammalian cytokines are ineffective in birds. PMID- 2575959 TI - Aerobic training effects on maximum oxygen consumption, lactate threshold and lactate disappearance during exercise recovery of dogs. AB - 1. Dogs were submitted to an aerobic training schedule and its maximum oxygen consumption, lactate threshold and lactate concentration during recovery were compared among the following conditions: not trained (UT), after 1 month of training (T1), after 2 months of training (T2) and after detraining (DT). 2. Maximum oxygen consumption increased significantly in relation to UT condition only at T2 condition. The detraining reversed this alteration. 3. Lactate threshold when expressed as Vo2 or absolute work load increased significantly after aerobic training (T2) but did not present any alteration when it was expressed as % of Vo2 max. 4. The lactate decreasing during recovery did not differ between the four experimental conditions (after 10 min). 5. The latency time for the lactate concentration to reach the top values was reduced by aerobic training (T2). PMID- 2575960 TI - Chronic in situ monitoring of the free calcium ion concentration in the uterine tubes and horns of the sheep. AB - 1. A system was developed for the chronic implantation of Ca2+ selective electrodes in the uterine horns and tubes of ovariectomised ewe. 2. Recordings were made over a 3-week period. 3. Resting free [Ca2+] was of the order of 1 mM. 4. Progesterone increased only the uterine horn [Ca2+], whereas oestrogen caused a transient rise only in the tubal [Ca2+]. PMID- 2575961 TI - Avian gonadotropin-releasing hormones I and II in brain and other tissues in turkey hens. AB - 1. Radioimmunoassays were developed for measuring avian gonadotropin-releasing hormones I and II (cGnRH I and II) in tissue extracts during the reproductive cycle. 2. Hypothalamic concentrations of cGnRH I and II were qualitatively similar being lowest in non-photostimulated hens, greater in laying hens and greatest in incubating hens. 3. cGnRH II concentrations were similar in paraolfactory lobe and hypothalamic fragments while lesser amounts were found in cerebrum, cerebellum, duodenum, shell gland, and pineal. 4. These results suggest that cGnRH II has unknown functions in turkeys quite distinct from traditional functions associated with GnRHs. PMID- 2575962 TI - Mandibular fluoride concentration and its relation to age in roe deer (Capreolus capreolus L.). AB - 1. Mandibular fluoride content was recorded in 63 roe deer (33 males, 30 females) between 9 months and 10 years of age, taken from an area in SW Germany not exposed to increased fluoride deposition. 2. Bone fluoride level was positively correlated with age (t-test, P less than or equal to 0.001), the increase in concentration being higher in younger animals and declining in older deer. 3. In the sample studied, no significant sex specific difference in mean mandibular fluoride concentration was found (t-test, P greater than 0.05). PMID- 2575963 TI - Serum cortisol levels in camels (Camelus dromedarius) during the reproductive cycle. AB - 1. Cortisol concentrations were measured in sexually mature female camels (N = 18), two newborn camels and one adult male. 2. The study revealed a significant difference in the amounts of cortisol in pluriparous mated camels (N = 7) during the breeding season before (8.0 +/- 1.3 ng/ml) and immediately after mating, 45.0 +/- 11.9 ng/ml (P less than 0.01). 3. At the start of parturition (N = 7), the maternal serum cortisol level rose suddenly from the basal value, 11.4 +/- 1.3 ng/ml, 3 days pre partum, to 45.3 +/- 5.0 ng/ml (P less than 0.005). 4. Immediately after birth, serum levels of cortisol in the newborn camels were 35.9 ng/ml and 37.0 ng/ml, respectively; in the dams, the concentrations of serum cortisol were 60.0 and 57.0 ng/ml, respectively. 5. In the female camels (N = 2) in seasonal anoestrus the amount of serum cortisol did not exceed 8 ng/ml. 6. During the breeding season the level of serum cortisol in the male was 1.15 ng/ml; 10 min post coitus the serum cortisol level rose to 9.92 ng/ml. PMID- 2575964 TI - Stimulatory activity of cysteamine on juvenile hormone release in adult females of the cockroach, Blattella germanica. AB - 1. A study of the activity of cysteamine in relation to juvenile hormone (JH) production in adult females of Blattella germanica was carried out. 2. In vivo assays showed that cysteamine stimulates protein synthesis in the left colleterial gland and, in some instances, enhances oocyte growth. 3. In vitro assays demonstrated that cysteamine enhances JH release by incubated corpora allata (CA), and that this effect is more pronounced when using CA from 10-day old females (period of ootheca transport), either connected to the corpora cardiaca (CC) or to the CC and to the brain. 4. Possible antiallatostatic effects of cysteamine are discussed. PMID- 2575965 TI - Independent pathways causing cellular damage in mouse soleus muscle under hypoxia. AB - 1. Mouse soleus muscle incubated in vitro released creatine kinase (CK) and underwent ultrastructural damage under hypoxic conditions. 2. Both events were exacerbated by contractile activity following field stimulation. 3. Ultrastructural damage preceded CK release. 4. Omission of extracellular Ca2+ protected against CK release whereas ultrastructural damage was unaffected. 5. Excessive contractile activity for 30 min under normoxic conditions caused myofilament damage, but this was not accompanied by CK release. 6. The results support the hypothesis that the pathways leading to myofilament breakdown and to CK release are separate and independent. 7. The results are discussed in relation to changes in the supply of high energy phosphates and consequently in the regulation of Ca2+-homeostasis under hypoxia. 8. Both pathways are believed to be triggered by rises in [Ca2+]i. 9. A high rate of oxygenation (10 ml sec-1) had no damaging effects, unlike its action on mouse diaphragm in vitro. 10. Since damage is exacerbated under N2, there is no evidence to support the view that O2 metabolites are necessarily implicated in cell damage in skeletal muscle. PMID- 2575966 TI - Insulin-like growth factor-I, GH, insulin and glucagon concentrations in bovine colostrum and in plasma of dairy cows and neonatal calves around parturition. AB - 1. The IGF-I concentrations in colostrum on days 1 and 2 after parturition were higher than those in cow and neonate plasma. 2. The modest increase in GH concentrations in cow plasma around parturition would not be enough to stimulate IGF-I release by tissues. 3. The concentrations of insulin, GH and glucagon in colostrum were substantially lower than those in plasma. PMID- 2575967 TI - Lower fat deposition and energy utilization of growing rats fed diets containing sorbose. AB - 1. Growing rats were fed diets containing graded levels (0, 100, 200 and 300 g/kg diet) of sorbose for 6 weeks. Protein, fat and energy deposition were determined by carcass analysis. 2. The values for growth, serum insulin level, digestible energy (DE), metabolizable energy (ME) and fat and energy deposition declined with the increment of dietary sorbose. 3. The efficiency of protein utilization (protein retained/protein consumed) was hardly affected by dietary sorbose. The DE and ME of sorbose per se was calculated as 14.09 and 12.35 kJ/g respectively. The efficiency of energy utilization (energy retained/ME intake) decreased with the increase of dietary sorbose, although sorbose had an ME. 4. The relative weights of gastro-intestinal tract and liver were positively associated with dietary sorbose level, although the reverse was true for the amount of stomach content, being heavier with higher dietary sorbose. 5. It is suggested that dietary sorbose, as a sweetener as well as a bulky agent, seems to be a suitable sugar for the obese and diabetic with special reference to lower body fat and energy deposition without reducing protein utilization. PMID- 2575968 TI - Altered adrenocortical response to acute stressors or ACTH(1-24) in intensively housed pigs. AB - In two experiments, the effect of intensive housing on behavior and adrenocortical reactivity was studied in 68 castrated male German Landrace pigs. In both experiments, half of the pigs were tethered on a partially slatted floor without straw and half were kept, as controls, in groups on straw. Prior to the study, 32 of the pigs used in the first experiment were selected according to their reaction to halothane anesthesia; for the second experiment, 36 pigs were selected according to their adrenocortical response to azaperone-metomidate anesthesia. During the 4- to 6-wk experimental period, behavioral activity was observed and adrenocortical reactivity was analyzed after stimulation with synthetic ACTH(1-24), azaperone-metomidate anesthesia, insulin-induced hypoglycemia and neostigmine-atropine. Although no difference was found in general activity between groups, tethered pigs revealed a significantly higher cortisol increase after stimulation with ACTH(1-24) in both experiments and after insulin stimulation in the second experiment. Similarly, the area below the cortisol response curve after ACTH stimulation was significantly larger in tethered pigs in the second experiment. The individual reaction pattern was positively correlated between tests, indicating this pattern is a relatively constant, individual characteristic. In contrast, no correlation was found between behavior or adrenocortical reaction pattern and sensitivity to halothane. The results suggest that tethering on a partially slatted floor constitutes a chronic stressor which changes the adrenocortical response to an additional acute stressor. This increased reactivity is revealed most clearly after stimulation with ACTH(1-24) when individual responsiveness is taken into consideration. PMID- 2575969 TI - Effect of triglycerides on growth hormone (GH)-releasing factor-mediated GH secretion in newborn calves. AB - The effect of triglycerides (Tg) on GRF-mediated GH secretion was examined in 2 groups of twelve ten-day old male calves. Twelve calves were intravenously infused with a lipid-heparin solution (5 mg Tg and 0.3 IU heparin/kg body wt/min for 90 min). The twelve control calves received in the same way, the same volume of saline. Thirty minutes after the start of infusion, GRF 1-29 (human amide, 0.16 micrograms/kg body wt) was intravenously injected in six animals of each group. Mean plasma GH levels reached peak concentrations in the 2 groups 5 min after GRF injection. However the area under the GH response curve, when lipid heparin was given, was significantly diminished compared to the response when saline was given. In the same time, lipid-heparin treatment increased plasma SRIF concentration. These data suggest that an increase in plasma Tg concentration, induced by lipid-heparin infusion, inhibits GRF-mediated GH secretion, possibly through stimulation of SRIF secretion. PMID- 2575970 TI - Regulation of nitrogenase activity by reversible ADP ribosylation. PMID- 2575971 TI - [The effect of prolyl-leucyl-glycine (MIF-1) and 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine on dopamine levels of the striatum]. AB - We report that large dose MPTP-treated mice bring about a reduction in the levels of DA, 5-HT and their metabolites in the striatum. In the mice pretreated with PLG, although the striatal DA level was also reduced, mean DA and 5-HT levels were significantly higher than in mice given MPTP alone. It is concluded that PLG can prevent, at least partially, the neurotoxic effect of MPTP. We assume that the mechanism of action of PLG may directly or indirectly reduce MPTP-induced dopaminergic neurotoxicity in the nigrostriatal system or reduce the affinity of MPP+ to melanin in DA cells. PMID- 2575972 TI - [Changes in humoral substances in induced cirrhosis and their effects on portal hemodynamics]. AB - The change of humoral substances in the blood of cirrhotic rat was studied at different stages of development, together with their effects on the portal hemodynamics. The profiles of humoral substances and hemodynamics in two different cirrhotic rat models, as well as the changes of portal hemodynamics in the normal rats after perfusion with the arterial blood from cirrhotic rats were also investigated. It was found that: during the development of cirrhosis, glucagon increased markedly at all stages, histamine and vasoactive intestinal polypeptide (VIP) increased at early stage only, while serotonin (5-HT) and somatostatin(SS) increased at middle and advanced stages. In the CCl4 induced cirrhosis, glucagon was the main humoral substance, whereas in the thioacetamide (TAA) induced cirrhosis, histamine and 5-HT were mainly elevated. The portal hemodynamics altered differently in different stages during the development of cirrhosis and in the two different cirrhotic rat models. The perfusion with the arterial blood from cirrhotic rats caused an increase of portal venous pressure and portal venous flow in normal rats. PMID- 2575974 TI - Patient preference in antianginal therapy. Proceedings of a symposium. Madeira, 21-22 October, 1988. PMID- 2575973 TI - Profile of an ideal antianginal agent. AB - Many antianginal agents are available for the treatment of coronary artery disease. These agents act by influencing the determinants of myocardial oxygen supply and demand. The 3 main classes of agents are the nitrates, beta-adrenergic blocking agents and the calcium entry blockers. Agents from all 3 classes have shown efficacy in treating both symptomatic and asymptomatic myocardial ischaemia. However, some patients cannot be treated with these agents because of side effects or contraindications. An ideal antianginal drug should effectively treat both angina and silent ischaemia. Additionally, it should be free of side effects, allow for maintenance of physical performance and be metabolically neutral. New agents are being developed which strive for this goal. PMID- 2575975 TI - Pharmacokinetics of epanolol (ICI 141,292) in healthy young volunteers and comparative data in elderly patients with angina and subjects with renal or hepatic impairment. AB - Single doses of epanolol (ICI 141,292) were administered to 12 healthy young male volunteers in a randomised crossover study. Each volunteer received a 200mg tablet, 200mg in solution or 5mg intravenously under fasting conditions, or a 200mg tablet with food. Venous blood samples were collected up to 72 hours after oral administration and 12 hours after intravenous administration. The concentrations of epanolol in plasma were determined by use of a radio immunoassay technique, whereas those in urine samples were measured by a high pressure liquid chromatographic (HPLC) method. Analysis of variance was used to assess the significance of the differences between the groups. Epanolol plasma concentrations declined biexponentially with time after an intravenous dose, with a half-life of 7 minutes for the first phase and about 3 hours for the second. Plasma clearance was high (2.1 L/min). Peak plasma concentrations of about 30 to 40 ng/ml were observed at mean times of about 1 to 1.5 hours after oral administration. After the peak, plasma concentrations declined biexponentially, with a terminal phase half-life of about 20 hours. The bioavailability of epanolol for the tablet and solution administered to fasted volunteers was similar (7-8%), but it was about 25% lower when administered as a tablet with food. Urinary recovery of epanolol was about 25% of the administered intravenous dose, but recoveries were much lower (about 1%) following oral administration. These data have been compared with those obtained after single oral doses of epanolol 200mg to elderly patients with angina and subjects with renal or hepatic impairment. PMID- 2575976 TI - Clinical pharmacology of epanolol. Pharmacodynamic aspects. AB - Epanolol has been shown in animal models to be a selective beta-adrenoceptor partial agonist with agonist activity about 20 to 25% of that of the full agonist isoprenaline. Evidence is presented in this review supporting the conclusion that epanolol has the same pharmacological properties in man and that the agonist activity at the beta-adrenoceptor is less than the activity present in pindolol, but greater than that present in acebutolol. The pharmacodynamic consequences in man of the degree of agonist activity possessed by the beta 1-selective partial agonist epanolol include little reductions at rest in heart rate, blood pressure, various measures of cardiac haemodynamic parameters, peripheral blood flow and renal function. On exercise there is attenuation of the heart rate and systolic blood pressure responses, with less perceived exertion than with atenolol. Evidence is available which shows that attenuation of the tachycardia of exercise persists for 24 hours after a single dose of epanolol 200mg, a dose which retains selectivity for the beta 1-adrenoceptor. This pharmacological profile of epanolol in man suggests that it would be an effective antianginal agent when 200mg once daily is administered. Moreover, its unique profile (compared with other antianginal agents) may make it more tolerable to patients than existing antianginal therapy. PMID- 2575977 TI - Epanolol. A new once-daily antianginal agent: dose finding and long term efficacy. AB - Epanolol is a new once-daily agent for the treatment of angina pectoris. This study was conducted in 2 parts. Firstly, a dose-finding study was performed using placebo and epanolol 100, 200, 300 and 400mg to assess the efficacy and safety of the drug. Once-daily epanolol 200mg was an effective dose, significantly reducing angina attack rate and increasing exercise duration and work output. At the same time, an improvement was noted in the patients' well-being and their ability to undertake normal daily activities. The 200mg dose regimen was used in a long term (12 months) assessment of the efficacy and safety of epanolol in the second part of this study. The efficacy of epanolol was clearly maintained throughout the full treatment period without adverse events or withdrawals as a result of treatment. The effectiveness and safety of epanolol are attributed to its selective beta 1-partial agonist activity. At rest, the degree of agonist activity (about 20% of that of isoprenaline) may prevent some of the untoward effects occasionally seen with full beta-blockers. During exercise, the antagonist activity becomes apparent and cardiac ischaemia is reduced. PMID- 2575978 TI - Dose finding in angina--results with epanolol. PMID- 2575979 TI - Effect of partial agonist activity on the side effects of beta-blockade in patients with chronic stable angina. AB - Some side effects of the beta 1-adrenoceptor blocker atenolol may result from depression of cardiac output at rest. They may, therefore, be reduced by the use of drugs with beta 1-partial agonist activity, such as epanolol. We compared once daily atenolol 100mg and epanolol 200mg in 20 patients reporting side effects while taking atenolol for chronic stable angina. A double-dummy, double-blind, crossover design was used to assess side effects by use of visual analogue scales and interviews, and antianginal efficacy by treadmill exercise tests and diary cards. In a comparison with atenolol, no significant differences in exercise time (686 +/- 11 seconds vs 685 +/- 10 seconds, maximum ST depression (1.02 +/- 0.09mm vs 1.07 +/- 0.08mm), time to 1mm ST depression (8.4 +/- 1.9 minutes vs 9.0 +/- 2.0 minutes), or days without angina (median 100% in both) were shown. All visual analogue scores were higher with epanolol (subjective energy 58.3 +/- 1.7 vs 54.3 +/- 1.5, well-being 61.8 +/- 1.8 vs 58.6 +/- 1.5 and warmth of extremities 68.4 +/- 3.6 vs 62.0 +/- 3.1). Although these differences did not attain statistical significance, 11 patients expressed a preference for epanolol and only 6 for atenolol. We conclude that, in this study, epanolol is as effective as atenolol as an antianginal agent for chronic stable angina. It improved the side effect profile in some but not all patients. PMID- 2575980 TI - Results of a long term multicentre study in Sweden. PMID- 2575981 TI - Rationale and statistical methodology for the VISA studies. AB - After examination of the epanolol ('Visacor') clinical package it became clear that, although efficacy and safety of epanolol were equivalent to efficacy and safety with other antianginal therapies, tolerability was improved. It was decided to initiate 2 studies with 500 patients in each to quantify the improved tolerability and examine patient preference for antianginal treatments. One study was a comparison of epanolol 200mg daily with metoprolol 100mg twice a day and the other compared epanolol 200mg daily with nifedipine retard 20mg twice a day. The rationale, design and statistical methodology are presented, together with a summary of the geographical spread of the study. PMID- 2575982 TI - Comparative multicentre study of the tolerability and efficacy of epanolol versus metoprolol in patients with stable angina pectoris. AB - The tolerability of epanolol, a new antianginal agent given as a single daily oral dose of 200mg, has been compared with the oral formulation of metoprolol (100mg twice daily) in a multicentre, randomised, double-blind, crossover study in 573 patients with stable angina (VISA 1). Patient preference for treatment was determined and efficacy was also monitored. Four weeks' treatment with one agent was followed by 4 weeks' treatment with the alternative agent. At the end of the study, patients were asked to express a preference, where possible, for 1 of the 2 treatments. The preliminary results of the study show that the preference question was answered by 524 patients (91.9%), and although 30 more patients preferred epanolol (45% preferred metoprolol, 55% preferred epanolol), the trend did not reach statistical significance (p = 0.137). Reasons for preference for epanolol were largely based on patients having fewer adverse effects, with fewer angina attacks and a general improvement in well-being as secondary reasons. Reasons for preference for metoprolol, however, were evenly divided between fewer adverse effects and fewer angina attacks, with a general improvement in well being of less importance. Responses to a tolerability questionnaire consisting of 43 questions on 7 different body systems showed that epanolol had a significantly better profile than metoprolol for 10 of the side effects, particularly those associated with beta-blocker treatment. Responses to only one question indicated that patients tolerated metoprolol better than epanolol. Two patients died during the study (one on metoprolol treatment and one on epanolol treatment). Neither death was attributed to the study treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575983 TI - Comparative multicentre study of the tolerability and efficacy of epanolol versus nifedipine in patients with stable angina pectoris. AB - The primary aim of this multicentre, randomised, double-blind, crossover study in 529 patients with stable angina pectoris was to compare the tolerability of epanolol, a novel antianginal agent, administered as a single oral daily dose of 200mg, with an oral retard formulation of twice-daily nifedipine 20mg and to determine patient preference (VISA 2). Confirmation of equal efficacy and safety monitoring were secondary aims of the study. Treatment consisted of 4 weeks on each therapy, and at the end of the study each patient was asked to state their treatment preference. 448 patients (85%) answered the preference question. Preliminary analysis of the data showed that 61% of patients preferred epanolol vs 31% who preferred nifedipine (p less than 0.001). Reason for a preference for epanolol were mainly fewer adverse experiences (11% vs. 23% with nifedipine), a general improvement in well-being (16% vs 10% with nifedipine) and a decrease in the number of angina attacks (11% vs 10% with nifedipine). A tolerability questionnaire comprising 43 questions and covering 7 different body systems showed that epanolol had a better profile than nifedipine for the following 7 side effects: poor sleep, abdominal pain, flushing, swollen ankles, palpitations, headache and a general feeling of being unwell. Four patients died during the study; none of the deaths were associated with the study treatment. Treatment with nifedipine resulted in 63 patient withdrawals compared with 31 patient withdrawals during epanolol treatment; there were 5 patient withdrawals from both treatments. The main reasons for withdrawal of patients from nifedipine treatment were adverse events (9% vs 4% with epanolol) and a lack of efficacy (3% vs 2% with epanolol).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2575984 TI - Efficacy of epanolol versus metoprolol in angina pectoris. Results from the Swedish Multicenter Study of Exercise Tolerance. The Swedish Multicenter Study Group. PMID- 2575985 TI - Effects of epanolol and metoprolol on the heart measured by 24-hour holter monitoring. AB - Continuous 24-hour ECG monitoring was performed as an additional objective in 87 patients from 5 centres in the VISA 1 study. The aim of the study was to compare the continuous 24-hour ECG recordings before the study and during treatment with epanolol ('Visacor') or metoprolol. Parameters of particular interest were heart rate and premature ventricular contractions (PVCs). Using the Oxford 4000 system with a 5-lead recorder, 24-hour monitoring was carried out on entry to the study (no antianginal therapy was allowed, with the exception of short acting nitrates), and at the end of both treatment periods. Measurements included the total number of heart beats and PVCs and the incidence of bradycardia. 87 patients, of mean age 59 (range 32 to 80) years, were included in the study. 62 patients had evaluable tapes available on both active treatment periods. The mean heart rate during 24 hours was significantly lower with metoprolol compared with epanolol treatment (64 vs 72 beats/min, respectively, p less than 0.001). The total number of PVCs in 24 hours was similar in both treatment groups and not significantly different from the value recorded at entry. The median total duration of bradycardia (heart rate less than 60 beats/min) in 24 hours was significantly (p less than 0.001) less for epanolol (60 minutes) than metoprolol (428 minutes). Plots of the mean hourly heart rates show that during daytime, epanolol was associated with a mean heart rate in between the rate observed without treatment and with metoprolol treatment. At night-time, almost identical values were found in the groups treated with epanolol compared with the non treatment period, whereas the metoprolol treatment induced significant lower heart rate levels. Thus, it was shown that there was greater heart rate reduction with metoprolol than with epanolol (p less than 0.001), and that there was no heart rate reduction at night with epanolol. No arrhythmogenic effect was seen for either drug. PMID- 2575986 TI - Left ventricular function during treatment with either metoprolol or epanolol. PMID- 2575987 TI - The effects of epanolol on quality of life. AB - The concept of quality of life is used to determine clinically relevant aspects of subjective symptoms and well-being, and refined psychometric instruments are now being developed to assess changes in well-being during pharmacological therapy. In order to evaluate general well-being, subjective symptoms and common side effects during cardiovascular therapy, workers at this hospital have designed a quality of life questionnaire. This consists of a generic section for the evaluation of 3 global aspects of well-being (hedonic tone, activity and relaxation) and a specific symptoms section for assessing 21 common side effects of cardiovascular drugs. The test is based on visual analogue scales. This questionnaire was used in a Swedish subsample (n = 211) of the epanolol versus metoprolol study in patients with stable angina pectoris (VISA 1). In this double blind crossover study, there were no significant differences between epanolol and metoprolol as regards general well-being with this sample size. The frequency of some specific symptoms (fatigue, sleep disturbances, vivid dreams and cold digits) was somewhat lower during epanolol treatment, but the differences did not attain statistical significance. PMID- 2575989 TI - Blood pressure control and mortality--is there a J-shaped curve? PMID- 2575988 TI - An overview of clinical trial experience with epanolol. AB - This overview of the safety and efficacy of the antianginal agent epanolol presents key features of the data from an international trial programme involving 1274 subjects. Additional information on the most frequently occurring possible adverse reactions is drawn from 2506 patients, which includes those in ongoing studies. Pooled analyses show that epanolol is as effective as reference therapies (nifedipine and atenolol), as assessed by work output during exercise tests, and in studies of anginal attack rate or work output during 12 months of treatment there was no evidence of tachyphylaxis with epanolol. Epanolol has a favourable safety profile, which compares well with those for placebo and for active antianginal therapies. PMID- 2575990 TI - Effects of beta-adrenergic blockers with different ancillary properties on lipid peroxidation in hyperthyroid rat cardiac muscle. AB - To determine whether beta-blockade protects rat heart against thyroxine (T4) induced accelelation of lipid peroxidation, in vivo effects of 3 beta-blockers with different ancillary properties on the mitochondrial oxidative enzyme, antioxidant enzymes and lipid peroxide were investigated. The rats were rendered hyperthyroid by adding T4 to their drinking water for 3 weeks and were treated simultaneously with either carteolol (a blocker with partial agonist activity; 30 mg/kg/day), atenolol (50 mg/kg/day) or arotinolol (a blocker with weak alpha blocking action; 50 mg/kg/day). The T4-induced tachycardia was alleviated completely by either atenolol or arotinolol, but only partially by carteolol. Cytochrome c oxidase activity in the heart muscle was increased by T4 with a parallel increase in manganese (mitochondrial) superoxide dismutase. Atenolol, but neither carteolol nor arotinolol, suppressed this increase. Similarly, the T4 induced acceleration of lipid peroxidation was suppressed by atenolol alone. Glutathione peroxidase was markedly decreased, and both copper zinc (cytosolic) superoxide dismutase and catalase were also decreased or tended to be decreased by T4. The levels of these 3 enzymes were only minimally affected by the beta blocker treatments. These results suggest that beta-blockade suppresses mitochondrial hypermetabolism and protects heart muscle against oxidative stress in hyperthyroidism, and that the ancillary properties of beta-blockers such as partial agonist activity and alpha-blocking action negate the protection. PMID- 2575991 TI - TSH-binding inhibitor immunoglobulin (TBII) in thyroidal venous blood and histological grade of intrathyroidal lymphocyte appearance in Graves' disease. AB - The aim of this study is to investigate the possibility of determining the appropriate amount of thyroid tissue to leave behind as remnant weight in subtotal thyroidectomy for Graves' disease by measuring the TBII value, and correlating the outcome to the grade of intrathyroidal lymphocyte infiltration. We therefore have investigated the levels of TBII in the thyroidal (T-TBII) and peripheral (P-TBII) venous blood, and the grade of lymphocytic infiltration and lymph follicle formation in the intrathyroidal tissue. There was no parallel relationship between the T-TBII value and the grade of lymphocytic infiltration and lymph follicle formation. There was no marked difference between the T-TBII value and the P-TBII value. It was thus not possible to use these data to determine the proper remnant weight of Graves' thyroid tissue at the time of surgery. PMID- 2575992 TI - Flow-dependent regulation of coronary vasomotor tone. AB - Large coronary artery calibres are regulated by humoral factors (autacoids) released from the endothelial cell lining. Several hormones, transmitters and platelet-derived products like serotonin and ATP or acetylcholine, noradrenaline, and histamine, stimulate such an autacoid release and thus an endothelium mediated dilation in addition to their direct constrictor effect on the vasculature. Another mechanical stimulus is the flow-induced shear stress acting as viscous drag upon the endothelial surface along with the pulsatile stretching of the endothelial lining, which causes, in a moment to moment fashion, a continuous adjustment of coronary calibres. With endothelial function impaired or absent as in atheromatosis or after balloon catheter denudation this adjustment is compromised. Thus unbalanced constrictor effects may become effective especially in the presence of a simultaneously reduced platelet antiaggregation. PMID- 2575993 TI - Selective effects of [D-Ser2(O-t-butyl),Leu5]enkephalyl-Thr6 and [D-Ser2(O-t butyl),Leu5]enkephalyl-Thr6 (O-t-butyl), two new enkephalin analogues, on neurotransmitter release and adenylate cyclase in rat brain slices. AB - The selectivity and potency of two new enkephalin-derived delta-opioid receptor agonists, DSTBULET ([D-Ser2(O-t-butyl),Leu5]enkephalyl-Thr6) and BUBU ([D-Ser2(O t-butyl),Leu5]enkephalyl-Thr6(O-t-butyl] were determined with functional tests in vitro of mu-, delta- and kappa-opioid receptor activation in the rat brain. Both peptides concentration dependently (1 nM-1 microM) inhibited the release of radiolabeled acetylcholine (ACh) from striatal slices (pD2 7.6-7.9), an effect exclusively mediated by delta-opioid receptor activation. Fentanyl isothiocyanate (FIT), an irreversible delta-antagonist, completely blocked the inhibitory effects of DSTBULET and BUBU. Up to a concentration of 1 microM, the peptides did not affect striatal [3H]dopamine (DA) release nor cortical [3H]noradrenaline (NA) release, processes which are known to be inhibited by opioids activating kappa and mu-receptors, respectively. Furthermore, both DSTBULET and BUBU caused a strong inhibition (pD2 8.2-8.3) of D-1 dopamine receptor-stimulated cyclic AMP efflux from striatal slices, an effect known to be mediated by mu- and/or delta opioid receptor activation. However, the peptides were without effect when D-1 and D-2 dopamine receptors were stimulated simultaneously, a situation in which only mu-agonists are able to inhibit the resulting cAMP efflux. In conclusion, DSTBULET and BUBU appear to display a high selectivity and potency toward functional delta-opioid receptors in the brain. PMID- 2575994 TI - Response of rat globus pallidus neurons to microintophoretically applied mu and kappa opioid receptor agonists. AB - The effects of the microiontophoretic application of dynorphin A-(1-13) (DYN 13) and the benzomorphans ethylketocyclazocine (EKC), bremazocine and MRZ 2549, (kappa) opioid agonists, and of morphine and morphiceptin, (mu) opioid agonists, were compared on spontaneous or glutamate-evoked discharge of globus pallidus (GP) neurons in rat. Our results demonstrate that mu and kappa opioid agonists are able to depress the excitability of pallidal neurons, possibly by interacting with mu and kappa opioid receptor subtypes, respectively. In addition, the mu agonists and dynorphin A-(1-13), but not the benzomorphans, enhanced the excitability of a number of pallidal neurons. We have proposed a presynaptic site as the basis for this opioid-induced excitation, possibly also mediated by a mu opioid receptor. The selectivity of dynorphin A-(1-13) for benzomorphan kappa opioid receptors in the rat GP appears to be low and dynorphin A-(1-13) may elicit effects that are different from those produced by the benzomorphan kappa agonists by virtue of its ability to interact with other opioid receptor subtypes, for example mu opioid receptors. PMID- 2575995 TI - Affinity profiles of BTM-1086 and BTM-1041 at muscarinic receptor subtypes and at H1- and alpha 1-receptors. AB - The affinities of the (+) and (-) enantiomers of the antimuscarinic benzothiazepinone derivative, cis-2,3-dihydro-3-(4-methyl-1-piperazinylmethyl)-2 phenyl-1,5-benzoth iazepin-4 (5H)-one (BTM-1041 and BTM-1086), for muscarinic receptor subtypes, histamine H1-receptors and alpha 1-adrenoceptors were determined in vitro using isolated organs: field-stimulated rabbit vas deferens (M1-receptors), guinea-pig left atrium (M2-receptors), guinea-pig ileum (M3- and histamine H1-receptors) and rat vas deferens (alpha 1-adrenoceptors). We also assessed the binding profile of BTM-1041 and BTM-1086 at muscarinic receptor subtypes in guinea-pig cortex (M1), heart (M2) and salivary glands (M3) as well as at alpha 1-adrenoceptors in rat cerebral cortex. Functional and binding experiments showed that the (-) enantiomer (BTM-1086) had a high affinity (pA2 = 7.98-8.81; pKi = 8.31-9.15) for the three muscarinic receptor subtypes, whereas the (+) enantiomer (BTM-1041) showed a low antimuscarinic potency (pA2 = 4.87 5.31; pKi = 4.85-5.55). This results in an extremely high stereoselectivity for these optical isomers [-)/(+) ratios = 1023 to 6918). The affinity of the (-) enantiomer BTM-1086 was lower for both histamine H1- and alpha 1-receptors than for muscarinic receptors, whereas the reverse was true for the (+) enantiomer, BTM-1041. Thus, the stereochemical demands for the two optical isomers were most stringent at muscarinic receptors but were inverse and less pronounced at histamine H1- and alpha 1-receptors (stereoselectivity ratios = 0.16-0.22). PMID- 2575996 TI - Acetylcholine is an indirect inhibitory transmitter in the canine ileocolonic junction. AB - The effects of cholinergic agents, electrical stimulation and vasoactive intestinal polypeptide (VIP) were studied on transverse muscle strips of the canine ileum, ileocolonic junction and colon. Acetylcholine, methacholine and carbachol caused concentration-dependent contractions in the three gut tissues. Only acetylcholine (greater than 10(-5) M) evoked transient relaxations in the ileum and the ileocolonic junction before the onset of contractions. During contractions by noradrenaline, acetylcholine induced relaxations, which were enhanced by atropine; electrical stimulation also caused frequency-dependent relaxations. Propranolol or naloxone did not affect the relaxations. Hexamethonium, cocaine or lidocaine inhibited the relaxations induced by acetylcholine but not those evoked by electrical stimuli. Tetrodotoxin inhibited all relaxations, VIP did not evoke relaxation in the ileocolonic junction. These data indicate that acetylcholine stimulates nicotinic receptors on non-adrenergic non-cholinergic neurons, which do not release VIP or opioids. It is thus suggested that there is a nicotinic inhibitory innervation at the canine ileum and ileocolonic junction. PMID- 2575997 TI - Intrinsic sympathomimetic activity of beta-adrenoceptor antagonists: down regulation of cardiac beta 1- and beta 2-adrenoceptors. AB - Prolonged treatment of cultured rat heart muscle cells containing beta 1- and non muscle cells containing beta 2-adrenoceptors with beta-adrenoceptor antagonists devoid of intrinsic sympathomimetic activity had no effect on beta-adrenoceptor density. In contrast, antagonists with intrinsic sympathomimetic activity decreased beta-adrenoceptor density and response (adenylate cyclase stimulation) in both heart muscle (beta 1) and non-muscle cells (beta 2) by a maximum of about 50%. An even larger down-regulation of beta-adrenoceptors and loss of receptor stimulated adenylate cyclase activity was induced by the full endogenous agonist, noradrenaline, with the beta-adrenoceptors of heart muscle cells (beta 1) being much more sensitive to the beta 1-selective noradrenaline than the heart non muscle cell beta 2-adrenoceptors. When combined with noradrenaline, the antagonists with intrinsic sympathomimetic activity prevented the action of noradrenaline at both beta 1- and beta 2-adrenoceptors, thereby leading to an apparent up-regulation of receptor density and response. This apparent reversal from an agonist to an antagonist action was observed at much lower concentrations of noradrenaline at beta 1- than at beta 2-adrenoceptors. The data presented indicate that the beta-adrenoceptor antagonists with intrinsic sympathomimetic activity, but not those without, upon prolonged treatment decrease the density and responsiveness of both beta 1- and beta 2-adrenoceptors in cultured rat heart cells. This suggests that the intrinsic sympathomimetic activity of these agents is not a subtype-selective component. Furthermore, the agonist and antagonist activity of these agents apparently depends on the concomitant presence of an endogenous full agonist and an its own affinity and that of the partial agonist for the beta-adrenoceptor subtype. PMID- 2575998 TI - Imidazolinic radioligands for the identification of hamster adipocyte alpha 2 adrenoceptors. AB - Imidazolinic radioligands ([3H]UK 14304, [3H]idazoxan and [3H]RX 821002) were used for the identification of alpha 2-adrenoceptors on hamster fat cell membranes since there are limitations to the use of [3H]yohimbine and [3H]clonidine, which suggest alpha 2-adrenoceptor heterogeneity. Biological assays (lipolysis measurements) were performed on isolated fat cells and binding studies were carried out on fat cell membranes. The imidazolinic derivative, UK 14304, was a full agonist as compared to clonidine. Idazoxan and RX 821002 (2-(2 methoxy-1,4-benzodioxan-2yl)-2-imidazoline), a recently developed alpha 2 antagonist, were more potent alpha 2-antagonists than yohimbine in this fat cell model. [3H]UK 14304 was the most suitable agent for the quantification of the 'high-affinity state' alpha 2-adrenoceptors in binding studies since it did not exhibit the sensitivity to the composition of the buffer shown by [3H]clonidine. Although it is a potent alpha 2-antagonist, [3H]idazoxan had major limitations for use in the identification of alpha 2-adrenoceptors in this cell model since it also bound to 'non-adrenaline displaceable' binding sites which were revealed when imidazolinic derivatives (phentolamine) were used instead of adrenaline to determine the non-specific binding. We demonstrated that [3H]RX 821002 was a more suitable radioligand than [3H]yohimbine for labelling hamster fat cell alpha 2 adrenoceptors (KD = 1.0 +/- 0.1 nM, Bmax = 776 +/- 60 fmol/mg protein). Moreover, since it exhibited low affinity for 'imidazoline-preferring sites', it represents a valuable ligand even in tissues possessing such binding sites. We suggest that [3H]RX 821002 can be used to identify alpha 2-adrenoceptors in various tissues when these sites cannot be labelled with [3H]yohimbine. PMID- 2575999 TI - The effects of dopamine D-1 and D-2 receptor agonists on body temperature in male mice. AB - The effect of dopamine D-1 and D-2 receptor stimulation on body temperature has been investigated in male mice. The selective D-2 receptor agonists, quinpirole and LY 163502, and the mixed D-1/D-2 agonist, apomorphine, induced a dose dependent hypothermia, whereas the selective D-1 receptor agonists, SK&F 81297, SK&F 38393 and SK&F 75670, induced hyperthermia. The hyperthermic responses of these agents were of a similar magnitude although the relative efficacies determined in vitro with the adenylate cyclase assay were different. The peripherally acting D-1 agonist, fenoldopam, did not influence body temperature, indicating that the hyperthermia is mediated, centrally. Studies with combinations of quinpirole and SK&F 38393 showed that the effect of one of the substances could be counteracted by the other. Furthermore, antagonist studies showed that the hypothermia induced by quinpirole could be inhibited by the D-2 selective antagonist, YM 09151-2, and by the mixed D-1/D-2 antagonist, cis(Z) flupentixol, but not by the D-1-selective antagonist, SCH 23390. Similar results were found for apomorphine-induced hypothermia. SK&F 38393-induced hyperthermia could be antagonized by all three antagonists. These results suggest that the two receptor subtypes act differentially on body temperature, and that they influence a common out-put system, but in opposite directions. These findings are opposite to those of behavioural studies, where a synergistic function of D-1 and D-2 receptors has been demonstrated in the regulation of motor function. PMID- 2576000 TI - Effects of seganserin, a 5-HT2 antagonist, and temazepam on human sleep stages and EEG power spectra. AB - The effects of seganserin, a specific 5HT2 antagonist, on human sleep were assessed in two experiments and compared to the effects of temazepam and sleep deprivation. During daytime recovery sleep after sleep deprivation, seganserin did not significantly enhance visually scored slow wave sleep (SWS, stages 3 + 4) or the EEG power density in the delta frequencies. Under these conditions temazepam reduced the power density in the delta and theta frequencies. During nighttime sleep after a nap in the evening, seganserin caused an increase in SWS, a reduction in intermittent wakefulness, and an enhancement of the power density in the delta and theta frequencies during non-rapid eye movement (NREM) sleep. Temazepam induced a reduction in the power density in the delta and theta frequencies. It is concluded that the 5HT2 antagonist, seganserin, can induce SWS. However, since the spectral results showed that the changes in the sleep EEG were not identical to those induced by sleep deprivation it seems premature to conclude that 5HT2 receptors are primarily involved in NREM sleep regulation. PMID- 2576002 TI - [The prevention of cardiovascular diseases]. PMID- 2576003 TI - [Hygiene instruction and education of the population in the prevention of cardiovascular diseases]. PMID- 2576001 TI - Renal hemodynamic responses to 5-hydroxytryptamine (5-HT): involvement of the 5 HT receptor subtypes in the canine kidney. AB - The study was designed to define the serotonin (5-HT) receptor subtypes in the canine kidney. An intrarenal infusion of 5-HT at a dose of 5 micrograms/min in anesthetized dogs resulted in a biphasic response of renal blood flow which decreased transiently then increased above the control level during prolonged infusion. The decrease of renal blood flow was abolished by infusion of methysergide but not by ketanserin, and the subsequent increase was abolished by infusion of either ketanserin or methysergide. Terazosin, an alpha1-adrenoceptor antagonist, did not modify the renal action of 5-HT. These findings suggest that the renal blood flow response induced by 5-HT did not depend on an indirect effect via the sympathetic nervous system, the initial vasoconstriction was mediated via a 5-HT1-like receptor, and that the latter vasodilatation was mediated via a 5-HT2 receptor. The infusion of 5-HT also increased urine flow and urinary excretion of sodium. These increases were reversed by pretreatment with ketanserin and abolished by methysergide. We propose that 5-HT may exert its antidiuretic action via a 5-HT1-like receptor in the tubules but that the renal hemodynamic changes induced by 5-HT may overcome its antidiuretic action. The present results suggest the existence of a 5-HT1-like and 5-HT2 receptor in the renal vasculature and a 5-HT1-like receptor in the renal tubules. PMID- 2576004 TI - [The quality control of the drinking water supply performed by the health officer's assistant]. PMID- 2576005 TI - Combined effect of growth hormone and cortisol on late posthypoglycemic insulin resistance in humans. AB - The occurrence and mechanisms for late (6.5- to 7.5-h) posthypoglycemic insulin resistance were studied with the euglycemic clamp in 19 healthy subjects. Comparisons were made with a control study with the same insulin infusion rate but where hypoglycemia was prevented by glucose infusion. Glucose production and utilization were studied with D-[3-3H] glucose infusions. Hypoglycemia induced marked insulin resistance shown by lower glucose infusion rates compared with the control study 3.1 +/- 0.3 vs. 6.0 +/- 0.7 mg.kg-1.min-1, P less than .001). This late posthypoglycemic insulin resistance was mainly due to a decreased insulin effect on glucose utilization. Infusion of propranolol did not prevent insulin resistance, whereas somatostatin partially prevented its appearance. Somatostatin plus metyrapone completely normalized posthypoglycemic insulin resistance. A positive correlation (r = .72, P less than .001) was found between initial insulin sensitivity and percent reduction of the insulin effect after hypoglycemia. Thus, hypoglycemia is followed by prolonged (6- to 8-h) insulin resistance. In contrast to early-phase (2- to 3-h) resistance, long-term resistance is not due to beta-adrenergic stimulation but to the combined effect of growth hormone and cortisol. This resistance is also more pronounced in subjects with initially high insulin sensitivity. PMID- 2576007 TI - Genetic control of diabetogenesis in NOD/Lt mice. Development and analysis of congenic stocks. AB - Genetic outcross and backcross analysis of nonobese diabetic (NOD/Lt) mice with a related but diabetes-resistant strain, nonobese normal (NON/Lt), has demonstrated that susceptibility to insulin-dependent diabetes mellitus is controlled in a recessive fashion by multiple genetic loci, including one (Idd-1s) associated with H-2 on chromosome 17 and another (Idd-2s) associated with Thy-1b/Apoa-1b (formerly Alp-1) on chromosome 9. To analyze the separate pathogenic contributions of Idd-1s and Idd-2s, two distinct congenic stocks of NOD/Lt mice homozygous on chromosomes 17 and 9 for NON/Lt linkage markers for the respective resistance alleles (Idd-1r and Idd-2r) were developed. The recessive nature of Idd-1s was confirmed at the fifth backcross generation in that 83% of females and 29% of males homozygous for NOD H-2 haplotype developed diabetes, whereas no diabetes occurred in any of the mice homozygous or heterozygous for the NON haplotype. However, codominant and recessive MHC-associated susceptibility genes in this congenic stock were indicated by the finding that at least one copy of the NOD/Lt MHC was required for insulitis development. Virtually no insulitis was detected in the pancreases of mice homozygous for NON haplotype at 42 wk of age, whereas heavy generalized insulitis was present in 3 of 19 H-2 heterozygotes and in 7 of 7 diabetic and 3 of 5 nondiabetic mice homozygous for NOD haplotype. Further indication of the presence of MHC-associated codominant and recessive MHC associated susceptibility genes was the observation that the NOD MHC haplotype correlated in a codominant fashion with a relative increase in the percentage of splenic T-lymphocytes bearing the Ly-2 surface marker. Severe insulitis and concomitant high diabetes incidences occurred in all genotypic classes of congenic mice carrying Thy-1/Apoa-1 linkage markers for either NOD or NON alleles at Idd-2. Molecular analysis indicated that the NON-derived Idd-2r resistance allele had been replaced by recombination with Idd-2s from NOD. Restriction fragment-length polymorphism analysis of two polymorphic markers proximal to Thy 1, low-density lipoprotein receptor Ldlr and Ets-1, a protooncogene, confirmed a recombinant chromosome 9, because homozygosity for NOD genomic fragments was found centromeric to an NON congenic segment of at least 20 centiMorgans spanning the Thy-1 and Mod-1 loci.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2576006 TI - Muscarinic stimulation and antagonism and glucoregulation in nondiabetic and obese hyperglycemic mice. AB - Plasma glucose and insulin responses to a muscarinic agonist (bethanechol chloride) and a muscarinic antagonist (atropine) were evaluated in obese C57BL/6J ob/ob mice and in lean C57BL/6J + /? mice. In lean +/? mice, plasma glucose decreased in response to 1 and 2 micrograms/g bethanechol chloride, whereas insulin increased significantly. In ob/ob mice, insulin increased remarkably in response to bethanechol administration (saline, 632 +/- 80 microU/ml; 2 micrograms/g bethanechol chloride, 1794 +/- 97 microU/ml; n = 10), but surprisingly, plasma glucose also rose significantly (saline, 230 +/- 14 mg/dl; 2 micrograms/g bethanechol chloride, 363 +/- 18 mg/dl, n = 10). This exaggerated hyperglycemia in ob/ob mice was not associated with significant changes in plasma glucagon. Furthermore, administration of propranolol hydrochloride did not diminish bethanechol chloride-induced hyperglycemia in ob/ob mice. Administration of atropine (2.5, 5, and 10 mg/kg body wt) induced a significant decrease in plasma insulin without changes in plasma glucose in ob/ob mice, whereas neither plasma insulin nor plasma glucose changed in lean mice. Finally, conversion of [14C]alanine to glucose was increased in ob/ob mice after bethanechol chloride administration, indicating that muscarinic stimulation increases gluconeogenesis in an animal model of type II (non-insulin-dependent) diabetes. PMID- 2576008 TI - One-month inhalation toxicity study of tulobuterol hydrochloride in rats and dogs. AB - Tulobuterol hydrochloride (HCl) has beta 2-adrenergic agonist activity and is under development for use in the treatment of chronic obstructive lung disease. The purpose of this study was to determine the toxicity of inhaled tulobuterol HCl in rats and dogs. Rats were whole-body exposed to aerosol gravimetric concentrations of 0, 0.03, 0.22, or 1.1 mg/liter of tulobuterol HCl, 60 min/day for 28 days. Dogs were exposed (via insufflation) to estimated daily doses of 0, 0.2, 1.0, or 6.0 mg/kg for an equal period. Plasma levels of tulobuterol were determined following exposure on Days 1, 8, and 28 using a high-pressure liquid chromatographic method developed for this study. Results indicated that plasma tulobuterol levels were highly correlated with tulobuterol doses (p less than 0.001 for rats and dogs). No dose-related changes in body weight food consumption, hematological, or serum chemistry parameters were observed in either species. Anterior nasal cavity lesions were observed by light microscopy in rats exposed to 0.22 and 1.1 mg/liter tulobuterol HCl at an incidence of 14 and 93%, respectively. These lesions involved the nasal septum, turbinates, and/or the dorsolateral wall of the nasal cavity and consisted of suppurative rhinitis and necrosis. The corresponding mean plasma tulobuterol levels on Day 28 in mid- and high-dose rats were approximately 1000 and 15,000 ng/ml. Nasal lesions were not observed in rats allowed to recover for 2 weeks. No gross or microscopic lesions were detected in lungs or other tissues of either species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576009 TI - Preclinical toxicology studies with nizatidine, a new H2-receptor antagonist: acute, subchronic, and chronic toxicity evaluations. AB - Nizatidine (NIZ), a new antiulcer drug, was evaluated for toxicity in acute, subchronic, and chronic tests. Acute toxicity studies were conducted in rats, mice, dogs, and monkeys. Median lethal doses (MLD) in rodents were greater than 1600, 230, and 1000 mg/kg by oral (po), iv, and sc administration, respectively. No deaths occurred in dogs given single doses of 800 mg/kg (po), 75 mg/kg (iv), or 225 mg/kg (im) or in monkeys given 1200 mg/kg (po) or 200 mg/kg (iv). Rats survived up to 1.0% dietary NIZ (daily intake ranging from 24 to 800 mg/kg/day) for 1 year. Slight decreases in body weight gain and increases in liver and kidney weights occurred. Slight decreases in erythrocytic parameters at 3 months were not present at 6 or 12 months. Mice survived up to 1.5% dietary NIZ for 3 months and effects were limited to slight decreases in body weight gain and increases in relative liver weight. Dogs survived oral doses up to 800 mg/kg/day for 3 months but had numerous clinical signs of toxicity and body weight loss. All dogs given oral NIZ doses up to 400 mg/kg/day survived except for one high dose dog that was killed in a moribund condition following convulsions in the 41st week of treatment. Effects in dogs included miosis, body weight loss, increased thrombocyte counts, and decreased hepatic microsomal enzyme activity and P450 content. The increase in thrombocyte counts was unaccompanied by changes in thrombocyte function and did not reoccur in a subsequent study. A decrease in plasma testosterone in two of three surviving male dogs given 400 mg/kg/day for 1 year was unaccompanied by effects on the size or morphology of testes or prostate. Peak plasma levels of NIZ in all species tested were in excess of human plasma levels after therapeutic doses. In conclusion, there was no evidence of significant toxicity in organs or tissues including those sites (gastric mucosa, male sex organs, and liver) that have been affected by some agents of this therapeutic class. PMID- 2576010 TI - BKm minisatellite sequences are not sex associated but reveal DNA fingerprint polymorphisms in rainbow trout. AB - GATA-GACA repetitive sequences first isolated from a female snake (termed BKm sequences) and associated with sex chromosomes in some species were hybridized to DNA from rainbow trout (Salmo gairdneri). Genomic DNA was studied from three groups of rainbow trout: (i) randomly selected males and females from an outbred group, (ii) androgenetic individuals from an inbred strain, and (iii) parents and offspring of an outbred strain. Three restriction enzymes (EcoRI, HaeIII, or HinfI) were used to digest the genomic DNA. The DNA was electrophoresed in agarose gels, transferred to nylon membranes, and the GATA-GACA repetitive sequence probe was hybridized to this DNA. There was no evidence of sex associated patterns of hybridization with the enzymes used. However, the sequences reveal DNA fingerprint polymorphisms which appear to be inherited in a stable manner. PMID- 2576011 TI - The mec-3 gene of Caenorhabditis elegans requires its own product for maintained expression and is expressed in three neuronal cell types. AB - The homeo-box-containing gene mec-3 of the nematode Caenorhabditis elegans, is expressed in several sensory neurons, as assayed by expression of a mec-3-lacZ fusion. These cells are the touch receptors, which mediate the response to gentle touch, and the FLP and PVD neurons. PVD mediates a response to harsh mechanical stimuli, and FLP has an ultrastructure suggestive of a mechanoreceptor, but its function is unknown. mec-3 is necessary for the differentiation of the touch receptors, because in mec-3 mutants, the touch receptors do not function and have none of their distinguishing features. mec-3 is also needed for PVD function: The PVD neurons no longer mediate a response to harsh mechanical stimuli in the mutants. The expression of the mec-3-lacZ fusion, and presumably mec-3 itself, is altered by mutations in several genes originally identified by their effects on touch cell development. unc-86, another homeo-box-containing gene, is necessary for all mec-3-lacZ expression, but also affects several other lineages and cells in which mec-3 is not expressed. mec-3 activity appears to be required for maintained expression of the mec-3-lacZ fusion in all cells in which it is expressed. In a mec-17 mutant, mec-3-lacZ expression is not maintained in the touch receptors, but is not affected in the FLP and PVD neurons. These findings suggest that combinatorial mechanisms of gene regulation control both the expression of mec-3 itself and its action in promoting the terminal differentiation of various cell types. PMID- 2576012 TI - Expression and embryonic function of empty spiracles: a Drosophila homeo box gene with two patterning functions on the anterior-posterior axis of the embryo. AB - Using the even-skipped homeo box as a probe to identify diverged homeo box genes in the Drosophila genome, we isolated the empty spiracles (ems) gene. Structural and functional comparisons between ems and other embryonic patterning genes of Drosophila suggest that ems acts, in part, as a homeotic selector gene, specifying the identity of some of the most anterior head segments. Mutant embryos lacking ems protein have severe patterning defects in the anterior head and are missing tracheal structures, including the filzkorper, which are normally developed by the eighth abdominal segment. ems has two different spatial patterns of expression during embryogenesis. The early, head-specific pattern consists of a single anterior stripe at the syncytial and cellular blastoderm stages. The later, metameric pattern consists of bilateral patches of ems expression in neural and ectodermal cells of every head and body segment. Variations of the ems expression pattern in bicoid mutants suggests that the morphogen protein produced by bicoid has a concentration-dependent regulatory role in the establishment of head-specific ems expression. In contrast, the metameric ems pattern is initiated independently of bicoid protein, and ems becomes expressed at high levels in the primordia of the duplicated filzkorper that develop in the anterior half of bicoid mutant embryos. PMID- 2576013 TI - Bicaudal-D, a Drosophila gene involved in developmental asymmetry: localized transcript accumulation in ovaries and sequence similarity to myosin heavy chain tail domains. AB - The Bicaudal-D (Bic-D) gene is essential for the differentiation of the oocyte in Drosophila. Dominant gain-of-function mutations result in the formation of double abdomen embryos. The Bic-D gene was cloned and identified using restriction fragment length polymorphisms, Northern analysis, and transformation rescue. Bic D RNA accumulates in the oocyte during the earliest stages of oogenesis and is localized anteriorly in later stages. The predicted protein contains several extended amphipathic helices, and its similarity to myosin heavy chain tails, paramyosin, and kinesin suggests a similar type of coiled-coil protein interaction. PMID- 2576014 TI - Type 1 fimbriae of Escherichia coli as carriers of heterologous antigenic sequences. AB - A strategy has been designed for the construction of recombinant bacterial strains which eventually may become useful as live vaccines and which may also be relevant for the preparation of conventional vaccines. The approach used is the fusion of small antigenic peptide sequences into specific segments of a protein whose location on the bacterial surface ensures that the recombinant organism is able to present the inserted antigen to the host (animal or human) infected by the bacterium. The chosen surface protein is a naturally occurring polymer of Escherichia coli, viz., type 1 fimbriae. The results obtained show that fusion of such foreign sequences into selected points of the structural protein of the fimbriae results in the production of functionally normal type 1 fimbriae. Furthermore, hybrid fimbriae carrying such small epitope sequences can be recognized by antibodies directed against the foreign parent protein. This observation is an important prerequisite for the eventual design of useful vaccines. The analysis of the fimbrial protein and its potential as a carrier of foreign peptides from hepatitis B surface antigen, foot-and-mouth disease virus and poliovirus indicated that there may be several positions in the protein which may turn out to be relevant for this purpose and be important fusion sites. PMID- 2576015 TI - Nucleotide sequence of the structural gene, tcpA, for a major pilin subunit of Vibrio cholerae. AB - The toxin co-regulated pilus (Tcp) of Vibrio cholerae appears to be a major protective antigen. By cosmid cloning we have isolated a number of clones capable of converting Tcp- El Tor strains of V. cholerae to Tcp+. A synthetic oligodeoxyribonucleotide probe based upon the N-terminal amino acid sequence of TcpA, has been used to localize the structural gene within the cosmid clones. Using suitable subclones, the nucleotide sequence of the tcpA gene has been determined. The gene encodes a 23.3-kDa pre-protein which in its mature form has a size of 20.3 kDa. The N-terminal leader peptide or signal sequence is atypical and does not conform with the usual rules of such sequences. The TcpA protein shows some similarities to the major pilins of the methylated phenylalanine type or type-4 pili from other bacteria; however, it is sufficiently different that it may represent a new class. PMID- 2576016 TI - [Neural modulation of immune system]. PMID- 2576017 TI - Milrinone enhances cytosolic calcium transient and contraction in rat cardiac myocytes during beta-adrenergic stimulation. AB - We have investigated the mechanism that underlies the absence of a positive inotropic effect of milrinone on rat myocardium. The twitch characteristics of enzymatically dissociated left ventricular myocytes from the adult rat and guinea pig were assessed by edge tracking during field stimulation. In some rat myocytes loaded with the ester derivative of the Ca2+ probe Indo-1 we simultaneously measured changes in cell length and in the associated cytosolic Ca2+ (Cai) transient. Our results show that in guinea pig myocytes bathed in 0.5 mM [Ca2+] and field stimulated at 1 Hz, milrinone (10 microM) had a positive inotropic effect. In contrast milrinone had no effect on the contractile properties of rat myocytes studied under similar conditions and field stimulated at 0.2 Hz. In rat myocytes bathed in 0.5 mM [Ca2+] and stimulated at 0.2 Hz isoproterenol (1 nM) increased the amplitude and shortened the duration of the contraction and of the associated Cai transient; these effects of beta-adrenergic stimulation were further enhanced by the addition of milrinone (10 microM) in the presence of isoproterenol. Under conditions of higher cell Ca2+ loading achieved by raising bathing [Ca2+] to 1 mM and isoproterenol to 3 nM the positive inotropic effect of milrinone (10 microM) in rat myocytes saturated when spontaneous oscillatory Ca2+ release appeared in the diastolic intervals between electrically stimulated twitches. Our results suggest that an enhancement in the baseline beta-adrenergic stimulation is required for milrinone to exercise a positive inotropic action on rat myocardial tissue. PMID- 2576018 TI - Rapid epidemiologic assessment of cataract blindness. The Aravind Rapid Epidemiologic Assessment Staff. AB - A major constraint to obtaining reliable information about blindness and its causes in developing countries is the limited availability of ophthalmologists for diagnosis in population-based surveys. This study in rural south India assessed the feasibility of using non-ophthalmologists to make diagnoses in a population-based survey. Ten men in their early twenties with 12 years of schooling were recruited and trained as ophthalmic assistants through a six week course in basic ophthalmology. All people aged 40 and older in households in 24 villages were enumerated and invited to have an eye examination. At a central site, 1309 subjects were independently examined by an ophthalmologist and two different ophthalmic assistants. Ophthalmic assistant cataract diagnosis is both sensitive and specific relative to the ophthalmologist's diagnosis. Sensitivity and specificity estimates were used to adjust prevalence estimates obtained from ophthalmic assistant examinations conducted at the central site as well as at the doorstep of sample households. The findings indicate that epidemiologic assessment of cataract blindness can be completed using non-ophthalmologists to diagnose cataract. PMID- 2576019 TI - Diagnosis, complications and treatment of Takayasu's arteritis. AB - Takayasu's arteritis is a large vessel vasculitis involving the aorta and it's major branches. Clinical diagnosis in the early stage is important as the disease may then be treatable. We present the first two cases ever reported in the Irish literature. PMID- 2576020 TI - Does T4 lymphocyte depletion predispose to HIV infection? PMID- 2576022 TI - Myocardial chronotropic and inotropic responsiveness in vitro after chronic alpha 1-adrenoreceptor blockade in the rat. AB - 1. Positive chronotropic and inotropic myocardial responses to different adrenoreceptor agonists were studied using isolated right atria and left ventricular papillary muscles from rats treated orally for 5 weeks with prazosin, an alpha 1-antagonist, or vehicle (distilled water). 2. Chronotropic responses to the beta-adrenoreceptor agonists isoprenaline and salbutamol were similar in atria from both groups of rats, with no differences in their basal rates, maximum rate increases or pD2 values for either agonist. 3. Basal contractile force of field-stimulated papillary muscles was similar in both prazosin-treated (0.089 +/ 0.014 g mg-1) and control groups (0.104 +/- 0.035 g mg-1). In response to noradrenaline, force increased maximally by 145 +/- 30% and 131 +/- 30% above resting levels respectively, and pD2 values for this beta- and alpha-agonist showed no changes after chronic prazosin treatment. Inotropic responses to isoprenaline were also not different with maximum increases in force of 94.5 +/- 20.2% for prazosin-treated and 84.5 +/- 18.5% for controls, and similar pD2 values. 4. However, in response to the alpha 1-agonist phenylephrine (in the presence of propranolol), maximum increases in force were greater in relation to the noradrenaline maxima after prazosin treatment (48.8 +/- 4.2%) than in controls (32.0 +/- 4.3%, P less than 0.02). pD2 values for phenylephrine were also significantly higher after long-term alpha 1-blockade (5.71 +/- 0.10 vs 5.30 +/- 0.19 for controls, P less than 0.05). 5. Long-term alpha 1-blockade in the rat therefore led to supersensitivity of alpha 1-mediated inotropism in the heart, but both beta-mediated inotropic and chronotropic responses were unaffected. These results show selectivity of action of chronic prazosin treatment on alpha 1-receptors in the rat heart. PMID- 2576021 TI - Relapsing spinal cord and cranial nerve syndromes in Takayasu's arteritis. AB - Isolated spinal cord and cranial nerve syndromes are extremely rare manifestations of Takayasu's arteritis and relapsing syndrome has not been described. A report of 31 year old lady is presented who had four distinct neurological syndromes over a period of six years with involvement of spinal cord and cranial nerves. Significance of this presentation is discussed. PMID- 2576023 TI - Effects of some antipsychotic drugs on cardiovascular catecholamine receptors in the rat. AB - 1. Experiments were performed to determine the activity of four antipsychotic drugs on several catecholamine receptors that control the sympathetic cardiovascular responses in rats. 2. Chlorpromazine, thioridazine (0.03 and 0.1 mg kg-1) and haloperidol (0.3 and 1 mg kg-1) inhibited methoxamine-induced diastolic blood pressure increases in the pithed rat, whereas sulpiride (1 and 3 mg kg-1) was without effect. 3. Only sulpiride (3 mg kg-1) antagonized the pressor responses induced by xylazine. 4. Xylazine inhibited the heart rate increase induced by electrical stimulation of the spinal cord (C7-Th1) in the pithed rat. This effect was partially prevented by sulpiride (1 and 3 mg kg-1) and chlorpromazine (0.3 mg kg-1). A higher dose of chlorpromazine (1 mg kg-1) abolished the inhibitory effect of xylazine. 5. Apomorphine infusion inhibited the pressor responses induced by electrical stimulation (Th5-L4) in pithed rats. This effect was reversed by sulpiride (0.01, 0.03 and 0.1 mg kg-1) and partially antagonized by haloperidol (0.1 mg kg-1). 6. The depressor response to fenoldopam in anaesthetized rats was only inhibited by the higher dose of chlorpromazine and thioridazine (3 mg kg-1). 7. Our results suggest that, in the peripheral nervous system of the rat, haloperidol and sulpiride act as antagonists of DA2 receptors while chlorpromazine and thioridazine antagonized DA1 receptors. Furthermore, thioridazine and haloperidol show alpha 1-adrenoreceptor antagonist properties, whereas sulpiride antagonizes alpha 2-adrenoreceptors. Chlorpromazine shows mixed alpha 1/alpha 2-adrenoreceptor antagonism. PMID- 2576024 TI - Prejunctional alpha 2-adrenoreceptors modulate the stimulated release of noradrenaline in isolated follicle strips from bovine ovaries. AB - 1. Strips from the follicle wall of bovine ovaries were incubated in Krebs-Ringer solution containing 3H-noradrenaline for measurement of transmitter liberation during electrical field stimulation (5 Hz frequency, 1 ms pulse duration, 10 V between the electrodes). The effects of noradrenaline as well as selective alpha adrenoreceptor agonists and antagonists were studied on the electrically induced efflux of radioactivity. 2. Noradrenaline (1 microM) inhibited the stimulated release of radioactivity. The alpha 2-adrenoreceptor agonist, oxymetazoline, significantly reduced the release of radioactivity in concentrations as low as 0.01 microM. The alpha 1-adrenoreceptor agonist, phenylephrine (0.01-1 microM), was without significant effect. 3. Phentolamine (0.01-1 microM) and the selective alpha 2-adrenoreceptor antagonist, idazoxan (0.01-1 microM) significantly enhanced the electrically evoked release. The alpha 1-adrenoreceptor antagonist, prazosin (0.01-1 microM), was without effect. Idazoxan (0.1 microM) reversed the inhibitory effect of oxymetazoline (0.1 microM). 4. It is concluded that administration of noradrenaline or the alpha 2-adrenoreceptor agonists reduces the release of labelled noradrenaline by acting on prejunctional alpha 2 adrenoreceptors in the noradrenergic nerves distributed in the wall of the bovine ovarian follicle. This is one of several prejunctional receptor mechanisms that modulate the activity of the sympathetic nerves innervating the smooth musculature of the follicle wall. PMID- 2576026 TI - The role of DNA-binding proteins in differentiation and transformation. PMID- 2576025 TI - Autonomic control of secretion of gastric acid and pepsin. PMID- 2576027 TI - Lymphoproliferative disease of granular lymphocytes in a patient with concomitant hepatitis B virus infection of CD4 lymphocytes. AB - In this report we studied a 35-year-old male who developed an abnormal expansion of granular lymphocytes (GL) which spontaneously regressed over a period of 2 years. The immunological and molecular characterizations of expanded cells showed the CD3+,CD8+,HNK-1+ phenotype, a polyclonal organization of the T-cell receptor beta-chain gene and normal natural killer activity. At the time of presentation, spot and blot hybridization techniques revealed the presence of viral hepatitis B virus (HBV) DNA sequences only in highly enriched CD4+ T cells, while proliferating GL were negative. With this as a background, we addressed the question of whether in our case the polyclonal GL proliferation represented an immunoreactive response against CD4+ infected cells. In particular, we tested the possibility that expanded GL could be cytotoxic against autologous infected CD4+ cells. At the time of the first determination, when several of the CD4+ cells harbored HBV, GL showed a minimal degree of cytotoxicity against 51Cr-labeled CD4+ cells; 2 years later, when GL became capable of lysing these targets, the appearance of the specific cytotoxicity was concomitant with the disappearance of the HBV-infected CD4+ cells and with the recovery of granular lymphocytosis. Taken together, our data suggest that in this case GL proliferation could represent an immunoreactive process against CD4+ cells. PMID- 2576028 TI - Blood levels of glucometabolic hormones and urinary saturation with stone forming phases after an oral test meal in male patients with recurrent idiopathic calcium urolithiasis and in healthy controls. AB - Male patients with recurrent calcium (Ca) urolithiasis (RCU) with idiopathic hypercalciuria (I-HC, n = 12) or normocalciuria (NC, n = 12), and age, sex, and weight-matched controls (C, n = 12) were evaluated before and after a carbohydrate-rich synthetic meal for blood glucose, free fatty acids (FFA), alpha amino-nitrogen, several glucometabolic hormones and parathyroid hormone (PTH), and urine Ca, phosphate, oxalate, and cyclic adenosine monophosphate (cAMP) levels as well as saturation. Fasting serum Ca was significantly higher and PTH significantly lower in I-HC than in controls, whereas in fasting urine cAMP and phosphate were unchanged. There were only minor differences between fasting blood glucose levels and postprandial glucose tolerance of RCU patients and controls. However, serum insulin was significantly elevated in I-HC versus C, but serum C peptide, plasma glucagon, and somatostatin levels were comparable in RCU and C. FFA were significantly lower in RCU than C. Postprandial phosphaturia and urinary saturation with Ca-phosphates were significantly higher in RCU versus C, whereas urinary cAMP, pH, and oxalate were similar. We conclude that: (1) in RCU patients some postabsorptive steps in glucose metabolism may be abnormal; (2) those with I HC have enhanced postprandial Ca and phosphate excretion concomitantly with disordered insulin metabolism; and (3) RCU patients may suffer from a postprandial renal phosphate leak, which may make their urine more lithogenic. PMID- 2576030 TI - High technology and tradition--both contribute. PMID- 2576029 TI - An embryonic Ca++ mobilizing muscarinic system in the chick embryo heart. AB - In the embryonic and in the adult heart muscarinic stimulation reduces the heart rate. Here we demonstrate that in the embryonic heart an additional muscarinic system is present, which is characterized by Ca++ mobilization and corresponds to the embryonic muscarinic system in other organ anlagen. In suspensions of embryonic chick heart cells we measured release of Ca++ from intracellular stores and influx of extracellular Ca++ with fura-2 and chlorotetracycline after muscarinic stimulation and determined the [3H]quinuclidinylbenzilate binding sites. We observed intense Ca++ mobilization at day 4, weaker reactions between day 4.5 and 11, and no Ca++ response at day 13. The pharmacological profile was identical to the profile of Ca++ mobilization in cells from other embryonic tissues in which the general embryonic muscarinic system is expressed. In parallel, we studied the effect of muscarinic agonists and antagonists on the heart rate of isolated embryonic hearts at day 4 and 5 in a perfusion chamber. Oxotremorine and bethanechol being antagonists or weak partial agonists in Ca++ mobilization, behaved as full agonists in frequency regulation. Thus, the pharmacological profile of the transient embryonic muscarinic system was different from that of the definitive adult form. PMID- 2576031 TI - [Prognostic factors in HIV seropositive children by materno-fetal transmission]. AB - Ninety-four cases with HIV seropositive children who were found in the Hospital Necker Enfants Malades in France from April 1983 till September 1988 due to materno-fetal transmission were surveyed for immunological studies as well as the relationship between clinical symptoms and the prognosis. Lymphoadenopathy and/or hepatosplenomegaly were found in 98% of the total cases. Opportunistic infections, severe neurological problems and LIP were found in 28%, 16% and 15%, respectively. At the first laboratory examination, cases showing under 500/mm3 of OKT4 lymphocytes and with negative antigen-induced proliferative responses were observed in 24% and 44% of the cases, respectively. Negative serological profiles of antibodies to P18 and P25 HIV antigens appeared to show low values of OKT4 lymphocytes and abnormal responses to antigens. The survival cases with these findings were minimum. These data indicate that it is very much worth, while to estimate the degree of immunological deficiency and infectious complications. PMID- 2576032 TI - Electron microscopy of adhesive interactions between Gardnerella vaginalis and vaginal epithelial cells, McCoy cells and human red blood cells. AB - Exfoliated vaginal epithelial cells with attached bacteria, termed 'clue cells', which were procured from a patient with non-specific vaginitis, were stained with ruthenium red and examined by transmission electron microscopy. The attached bacteria appeared to adhere by means of an outer fibrillar coat. An epithelial tissue culture cell line (McCoy) and human red blood cells to which strains of Gardnerella vaginalis attached were similarly examined. The adherence of G. vaginalis to the epithelial cell line appeared to be mediated by an outer fibrillar coat while adherence to red cells appeared to be mediated by fimbriae. Transmission electron microscopy was performed on the Gardnerella strains used. Thin sections of tissue-culture-adherent strains revealed a dense outer fibrillar coat whereas the surface of the haemagglutinating strains showed fine fimbriae. Negative staining of haemagglutinating strains demonstrated fimbriae on a minority of organisms. PMID- 2576033 TI - Properties of adherence factor plasmids of enteropathogenic Escherichia coli and the effect of host strain on expression of adherence to HEp-2 cells. AB - EPEC adherence factor (EAF) plasmids from three strains of enteropathogenic Escherichia coli (EPEC) - E2347/69 (O127:H6), E20517 (O111:H2) and E24582 (O142:H6) - were examined. The EAF plasmids were all marked with ampicillin resistance by transposition of Tn801 to give pDEP1, pDEP2 and pDEP11, respectively. All three plasmids showed incompatibility with an FIme and an FIV plasmid and had some similarity in restriction enzyme digest patterns. Plasmid pDEP1 differed from pDEP2 and pDEP11 in being autotransferring and fertility inhibition positive. An EAF probe consisting of a 1 kb BamHI-SalI restriction endonuclease fragment of the prototype EAF-associated plasmid pMAR2 hybridized to similar-sized SalI-BamHI fragments of pDEP1 and pDEP11 but to a different-sized fragment of plasmid pDEP2. Loss of the EAF plasmids from EPEC strains resulted in a marked reduction in the ability of these strains to adhere to HEp-2 cells. The EAF-plasmid-negative variants did not express a 94 kDa outer-membrane protein (OMP). When these EAF plasmids were reintroduced into EAF-plasmid-negative EPEC strains a high level of adherence equivalent to that of the parent EPEC strains was restored and a 94 kDa OMP was usually expressed. However, when EAF plasmids were transferred into E. coli K12 or non-EPEC E. coli the host strains either did not adhere or adhered poorly to the HEp-2 cells. These transconjugants did not express a 94 kDa OMP. PMID- 2576034 TI - Characterization of a putative colonization factor (PCFO166) of enterotoxigenic Escherichia coli of serogroup O166. AB - Enterotoxigenic Escherichia coli (ETEC) of serogroup O166 gave mannose-resistant haemagglutination (MRHA) with bovine and human erythrocytes. The strains did not react with antisera prepared against the known colonization factors CFA/I, CFA/II, CFA/III, CFA/IV and PCFO159:H4. Strain E7476 of serotype O166:H27, which produced heat-stable enterotoxin (ST), was examined initially. It produced fimbriae about 7 nm in diameter. On SDS-PAGE two possible fimbrial polypeptides of molecular mass 15.5 and 17.0 kDa were seen. When variants of strain E7476 were isolated, loss of ST and MRHA together was associated with loss of a 98 MDa plasmid, while loss of ST alone correlated with plasmid deletion. An absorbed anti-strain E7476 antiserum reacted specifically with the 15.5 and 17.0 kDa polypeptides in Western immunoblotting and bound to the intact fimbriae by immuno electron microscopy. When this antiserum was used in an ELISA to examine other strains of serogroup O166, a positive reaction was obtained with all the ST- and MRHA-positive strains. One strain of serotype O71:H27 and two strains of serotype O98:H- also reacted with the absorbed anti-strain E7476 antiserum. The antiserum did not react with ETEC carrying known colonization factors. E. coli K12 and a number of E. coli of different serotypes carrying a plasmid coding for ST transferred from strain E7476, all gave MRHA and reacted with the absorbed anti strain E7476 antiserum. The term putative colonization factor O166 (PCFO166) is proposed to describe the adhesive factor(s) on ETEC of serogroup O166 because of the similarity of properties with those of known colonization factors. PMID- 2576035 TI - Active immunization of homosexual men using a recombinant hepatitis B vaccine. AB - Twenty homosexual men [13 anti-human immunodeficiency virus (HIV)-positive, seven anti-HIV negative] without HBsAg, anti-HBs, and anti-HBc were vaccinated with three 20 micrograms doses of a recombinant hepatitis B vaccine. All anti-HIV positive homosexuals were nonresponders independent of the initial number of CD4 positive cells. Among seven anti-HIV-negative individuals, five responded. After three doses of the vaccine, CD4-positive cells fell in anti-HIV positive individuals by 22.4%. A similar fall in CD4-positive cells of an average 24.9% was noted in 17 matching, but nonvaccinated, anti-HIV-positive homosexuals. The study indicates that the efficacy of vaccination in anti-HIV-positive individuals is questionable. There is, however, no evidence that vaccination against hepatitis B might be harmful to anti-HIV-positive subjects. PMID- 2576036 TI - The long-term effects of a single injection of taxol upon peripheral nerve axons. AB - To study the long-term effects of a single injection of the microtubule stabilizing drug taxol in vivo, the compound was injected into rat sciatic nerve and the ensuing morphological changes followed for 8-25 weeks after injection. In accord with previously published works, taxol-induced giant axonal bulbs were common and were most marked at 8-10 weeks. From 12 weeks onwards these giant axons decreased in diameter with concomitant remyelination. By 20 weeks axonal bulbs could not be seen. The recovery of axons from taxol intoxication began 8-12 weeks after injection with the growth of axonal sprouts, longitudinally and laterally, from the distal aspect of the proximal stump. During recovery, from 12 weeks onwards, axons showed apparent reorganization of the axoplasmic cytoskeleton where microtubules diminished and neurofilaments became more numerous. By 16 weeks only small groups of microtubules remained, often encircling a mitochondrion. By 25 weeks taxol-treated nerves showed no apparent taxol-induced changes. A common ultrastructural finding up to 16 weeks was the appearance within axons of tubular profiles covered by a double membrane. These structures were sometimes arranged as crystalloid aggregates. The diameter of these profiles was 85 nm, they were most common at 12 weeks and it is proposed that they may be derived from mitochondria. The present results show taxol to have a long-lasting and local effect upon axoplasmic organization in vivo. The cytoskeletal reorganization described supports the concept of the differential movement of axoplasmic neurofilaments and that neurofilaments stabilize axonal structures. PMID- 2576037 TI - The long-term cellular response to taxol in peripheral nerve: Schwann cell and endoneurial cell changes. AB - Taxol, an agent known to stabilize and increase the assembly of microtubules, causes long-lasting nerve damage when injected into peripheral nerve. In the present study, the cellular response to taxol in rat sciatic nerve was studied for up to 6 months after a single injection. The initial response of Schwann cells to taxol at the lesion site involved the accumulation of cytoplasmic microtubules which persisted up to 4 months after injection. Some novel microtubule-related cytoplasmic structures were also noted; these included microtubule-lined cytoplasmic crypts and channels. Despite these structural abnormalities, Schwann cells were able to produce myelin sheaths around taxol induced axonal bulbs. This myelination showed some anomalies up to 4 months consisting of the widening of myelin lamellae, variability in sheath thickness, paranodal myelin infoldings and myelin protrusions. With time the diameter of the axonal bulbs decreased and, concomitant with this, more normal-appearing remyelination occurred. By 5 months, the previously noted myelin abnormalities were rare. By 6 months only a few naked axonal segments occurred at the lesion site. In endoneurial fibroblasts and macrophages cytoplasmic lamellar microtubule formations were frequent at 10 weeks. Needle-like cytoplasmic structures appeared within endoneurial cells at the site of the lesion after 10 weeks. By 3 months these inclusions were numerous and were often surrounded by extended cytoplasmic processes. The needles were up to 50 microns long and 3 microns wide and probably represented cholesterol. By 4 months the number of cytoplasmic needles decreased and at 5 months onwards none was observed. The present findings confirm and extend previous findings that taxol has a long-lasting effect upon both Schwann cells and endoneurial cells and that this is related to abnormal tubulin synthesis. PMID- 2576038 TI - The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. AB - Feeding rats diets containing oils that have a low alpha-linolenic acid [18:3(n 3)] content, such as sunflower oil, results in reduced amounts of docosahexaenoic acid [22:6(n-3)] in all brain cells and organelles compared to rats fed a diet containing soybean oil or rapeseed oil. During the period of cerebral development there is a linear relationship between the n-3 fatty acid content of the brain and that of food until alpha-linolenic acid represents approximately 200 mg/100 g food [0.4% of the total dietary energy for 18:3(n-3)]. Beyond that point brain levels reach a plateau. Similar values are also found for other organs. The level of 22:6(n-3) in membranes is little affected by the dietary quantity of linoleic acid [18:2(n-6)] if 18:3(n-3) represents approximately 0.4% of energy. In membranes from rats fed diets containing sunflower oil, Na+, K(+)-ATPase activity in nerve terminals was 60%, 5'-nucleotidase in whole brain homogenate was 80%, and 2',3'-cyclic nucleotide 3'-phosphodiesterase was 88% of that in membranes from rats fed diets containing soybean oil. A diet low in alpha-linolenic acid leads to anomalies in the electroretinogram, which partially disappear with age. It has little effect on motor activity, but it seriously affects learning tasks as measured with the shuttle box test. Rats fed a diet low in alpha-linolenic acid showed an earlier mortality in response to an intraperitoneal injection of a neurotoxin, triethyltin, than did rats fed a normal soybean oil diet. PMID- 2576040 TI - The disposition of the enantiomers of warfarin following chronic administration to rats: relationship to anticoagulant response. AB - A model of chronic anticoagulation has been used to investigate the whole liver and subcellular disposition of the individual enantiomers of warfarin in the Wistar rat in relation to anticoagulant response. Consistent pharmacodynamic responses were achieved by dosing daily with R-warfarin (0.4, or 0.8 mg kg-1 day 1 i.p.) or S-warfarin (0.1 mg kg-1 day-1 i.p.). After the administration of increasing doses of R-warfarin, prothrombin times were dose-dependent (16.3 +/- 0.5 s, 0.1 mg kg-1 day-1; 21.6 +/- 1.7 s, 0.4 mg kg-1 day-1; 55.1 +/- 9.0 s, 0.8 mg kg-1 day-1; results all measured 24 h after the final dose). Increasing doses of R-warfarin also produced increases in plasma, whole liver, and cytosolic concentrations of warfarin. However, there were no significant differences between the microsomal concentrations of R-warfarin in the three groups. The dose of S-warfarin required to produce a consistent and significant increase in the prothrombin time was four-fold lower than the dose of R-warfarin required to cause a similar effect. Plasma concentrations of S-warfarin were not significantly different from those seen after 0.4 mg kg-1 day-1 R-warfarin. Whole liver and cytosolic concentrations of the S-enantiomer were lower than those observed after a dose of 0.4 mg kg-1 day-1 R-warfarin. However, consistent with microsomal concentrations following increasing doses of R-warfarin, there was no significant difference between microsomal concentrations of R(+)- and S(-) warfarin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576039 TI - Formulation studies of tableted oral rehydration salt mixtures. AB - Dehydration following non-specific diarrhoea may be prevented by oral administration of a simple glucose/salt mixture. A solution tablet of this mixture would have advantages of stability under environmental exposure and transport if the costs could be held within reasonable limits. The moisture adsorption and compression characteristics of Oral Rehydration Salts (ORS) ingredients have been studied. Combinations of ingredients resulted in a moisture adsorption higher than that of the individual components. This may be explained in terms of critical relative humidity, RHo, and environmental relative humidity RHi. Preparation of a stable ORS solution tablet therefore requires protection of moisture adsorbing components from the environment. The present UNICEF ORS mixture compacted easily by direct compression but gave fragile tablets, which were hygroscopic. This can be reduced by film coating the electrolyte component as granules with a resin (Eudragit L), or by simulating direct compression of the glucose as a compression-coating around the precompressed electrolytes. The packaging of compression-coated solution tablets in inexpensive polyethylene bags may lengthen the shelf-life and make the preparation less costly than the currently supplied ORS powders packed in laminated aluminium sachets. The increased dissolution lag time for the compacted tablet is a disadvantage that can be overcome by instructions to crush the product immediately before use. PMID- 2576041 TI - Stimulation of gastric and colonic mucosal eicosanoid synthesis by plantain banana. AB - Extracts of plantain banana (Musa sapientum Linn var. paradisiaca) were studied on the accumulation of eicosanoids in incubates of human gastric and colonic mucosa. The ethanolic extract caused a concentration-dependent increase in the eicosanoid accumulation but the water extract was ineffective. Since all the eicosanoids studied tended to increase, banana may act by increasing the availability of arachidonate. In control tissues the accumulation of PGE and TXB2 in the incubates decreased with time while that of 6-keto-PGF1 alpha increased (colon only, studied). PMID- 2576042 TI - Excitatory effect of morphine and opioid peptides in the rat isolated colon. AB - Morphine and the opioid peptides cause isolated segments of rat colon to contract and relax rhythmically. This study re-examines two hypotheses to explain this phenomenon: Release of 5-hydroxytryptamine (5-HT)/acetylcholine by morphine or inhibition of a tonically active non-adrenergic, non-cholinergic (NANC) inhibitory mechanism. Rhythmic contractions induced by morphine (5 x 10(-6) M) were naloxone sensitive (10(-6) M) but unaffected by methysergide (10(-6) M), atropine (10(-6) M) or pretreatment of rats with p-chlorophenylalanine (200 mg kg 1 i.p. for four days) which lowered the 5-HT level in the colon from 3.73 +/- 0.83 mg g-1 in controls to 0.41 +/- 0.06 mg g-1 (P less than 0.001). The pattern of rhythmic contractions produced by morphine was unlike those produced by 5-HT (5 x 10(-6) M), acetylcholine (5 x 10(-6) M) or potassium chloride (30 mM). Tetrodotoxin (10(-6) M), apamin (10(-8) M), clonidine (2 x 10(-8) M), phentolamine (10(-5) M) or oxprenolol (10(-5) M) caused rhythmic contractions which were unaffected by naloxone. Clonidine contractions were inhibited by yohimbine (10(-7) M) but not by prazosin (10(-6) M). Electrical field stimulation at the peak of a contraction induced by morphine, apamin or clonidine, produced an inhibitory response which was unaffected by atropine, phentolamine, propranolol and guanethidine (all 10(-5) M). It persisted in colon segments from the rats with reserpine or 6-hydroxydopamine. These results suggest that neither the 5-HT/acetylcholine hypothesis nor inhibition of the NANC mechanism adequately explains the excitatory effect of morphine in the rat colon. PMID- 2576043 TI - On the relevance of non-steroidal anti-inflammatory drugs in the prevention of paralytic ileus in rodents. AB - In the mouse, the gastrointestinal transit of a charcoal marker, halved following the intraperitoneal administration of acetic acid, was no longer inhibited after pretreatment with the non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin, ketoprofen, piroxicam or ximoprofen (0.25-2.5 mg kg-1 orally). In the fasted rat, the migrating myoelectric complex pattern of the small intestine which was disrupted for about one hour by acetic acid was unaltered by pretreatment with indomethacin or ximoprofen (0.5 mg kg-1 i.p.). In the anaesthetized rat, the inhibition by about 50% of the gastrointestinal transit due to laparotomy, did not occur following treatment with NSAIDs. It is concluded that NSAIDs prevent the occurrence of chemically-induced and postoperative ileus in rodents, an effect probably related to the analgesic properties of NSAIDs. PMID- 2576044 TI - Effect of meptazinol on evoked responses in rat vas deferens. AB - Responses of rat isolated vas deferens to electrical stimulation through field electrodes (400 mA, 1 ms duration, single shocks at 5 min intervals) were potentiated by meptazinol (10 to 300 microM) in whole tissues and also in the separated prostatic and epididymal portions. The effect was fast in onset, reproducible and easily reversed by washing. Prazosin (0.1 microM) practically abolished the response of the epididymal portion to electrical stimulation while the response of the prostatic portion was only slightly reduced (less than 20%). In the presence of prazosin, meptazinol still produced potentiation of the response of the prostatic portion. Nifedipine (2 microM) practically abolished the response of the prostatic portion to electrical stimulation while the response of the epididymal portion was only slightly reduced (less than 20%). In the presence of nifedipine, meptazinol no longer produced potentiation of the response of the epididymal portion. Exogenous ATP (5 microM to 1 mM) and phenylephrine (1 to 50 microM) produced a contractile response which was potentiated in the presence of meptazinol (100 microM) but in the presence of meptazinol (100 microM) and nifedipine (5 mM) together, potentiation of phenylephrine no longer occurred. It is suggested that potentiation by meptazinol of electrically induced responses in this tissue is due to a direct action on the smooth muscle. PMID- 2576045 TI - Blood pressure, the renin-angiotensin system and neurogenic vasoconstriction in pithed rats. AB - The influence of changing baseline blood pressure by various means, both related or unrelated to the renin-angiotensin system, on the pressor responses to spinal cord stimulation has been examined in the pithed rat. Mean arterial pressure and neurogenic vasoconstriction were higher in pithed rats with intact kidneys (2 kidney rats) than in nephrectomized pithed rats. Increasing blood pressure by infusion of vasopressin increased the pressor response to nerve stimulation in both 2-kidney and nephrectomized pithed rats. Decreasing blood pressure produced by administration of enalaprilat or hydralazine in 2-kidney pithed rats or by administration of hydralazine in nephrectomized pithed rats, decreased the pressor responses to nerve stimulation. Our results showed a positive correlation between the mean arterial blood pressure and the response to nerve stimulation in pithed rats. Therefore, we conclude that the pithed rat is an animal model which should be used with caution to study the interaction between the sympathetic nervous system and drugs which change baseline blood pressure. PMID- 2576046 TI - Rectal absorption of E-2078 (dynorphin analogue peptide) in rats. AB - The plasma levels in rats of a dynorphin analogue peptide (E-2078) after rectal administration have been studied. The bioavailabilities of E-2078 after rectal administration, subcutaneous injection, intramuscular injection, and oral administration were 21.6, 67.8, 67.1, 0.7%, respectively. The effect of dose, pH, osmolarity and viscosity on the rectal absorption of E-2078 were studied. A sigmoid relationship between the dose and the AUC was observed on rectal administration, while there was a linear relationship on intramuscular administration. The AUC was increased in acidic solution and highly viscous solution. The osmolarity did not affect the absorption of E-2078. In microscopic studies, E-2078 caused little or no damage to the rectal mucosa in rats. PMID- 2576047 TI - Biocompatibility of wound management products: standardization of and determination of cell growth rate in L929 fibroblast cultures. AB - To facilitate the development of a bioassay procedure by which the biocompatibilities of materials used in wound management may be assessed and compared, those environmental factors affecting cell growth in mouse L929 fibroblast cultures have been identified. Standardization of the initial cell number and frequency of change of medium resulted in the virtual elimination of variation of growth curves of L929 cells cultured in flasks of specified surface area. In addition, three methods for assessing fibroblast growth rate in the presence of alginate products used in wound management were evaluated. These were the haemacytometer counting chamber method, the Coulter counting method, and a liquid scintillation counting method. The first two methods determine the number of cells in a given volume of a cell suspension, whereas the third method determines the rate of synthesis of deoxyribonucleic acid (DNA), and hence cell growth, by measuring the incorporation of [3H]thymidine. The haemacytometer method had significant advantages over the other two procedures in providing both qualitative and quantitative data on culture morphology and cell growth response. PMID- 2576048 TI - Biocompatibility of wound management products: the effect of various monosaccharides on L929 and 2002 fibroblast cells in culture. AB - The effects of various monosaccharides on the growth of human 2002 and mouse L929 fibroblast cultures have been investigated. Eleven monosaccharides having acidic, neutral, and basic characteristics were evaluated in a bioassay procedure developed for the investigation of biocompatibility of wound management materials. Rate of growth in both cell lines was inhibited by D-galacturonic acid and by D-glucuronic acid. Although most neutral sugars produced no significant change in the growth rate or in the morphology of the cells, galactose produced a significant increase in the growth rate of both cell lines whilst L-fucose caused a significant decrease in growth of the L929 cells but did not significantly affect the growth of 2002 cells; xylose increased the growth rate of L929 but not 2002 cells. D-Glucosamine, a basic sugar, produced inhibition of growth which followed a different pattern from that produced by the acidic sugars; N acetylglucosamine produced a species specific increase in cell growth of L929 cells. The results show that the effects produced by the monosaccharides on the cultured fibroblasts are related to their chemical structure and to cell line, and suggest that the use of galactose as a possible aid to wound healing should be investigated. PMID- 2576049 TI - Suppression of pentobarbitone-induced hyperactivity by past experience in mice. AB - Locomotor activity of CD-1 mice, tested in an unfamiliar environment (toggle floor box), was increased either by a subhypnotic dose (20 mg kg-1) of pentobarbitone or after recovery from pentobarbitone-induced (50 mg kg-1) anaesthesia. On the contrary, when mice were tested 6 h after a single exposure to the apparatus, pentobarbitone in either case failed to produce hyperactivity. The results demonstrate that mice recovering from barbiturate anaesthesia maintain susceptibility to the exteroceptive stimuli provided by a novel environment and knowledge of the environment acquired during past experience. PMID- 2576050 TI - The plasma disposition of sheep antibody (Fab) fragments in the guinea-pig and rabbit. AB - The plasma elimination of sheep digoxin-specific Fab (fragment antigen-binding) antibody fragments has been studied after intravenous injection (1 mg kg-1) in guinea-pigs and rabbits using an enzyme-linked immunosorbent assay. The log concentration versus time profiles were best described by biexponential and triexponential functions for the response in the guinea-pig and rabbit, respectively. However, the elimination half-lives and apparent volumes of distribution were similar in both species (about 140 min and 120 mL kg-1, respectively). The value for the Fab distribution volume suggests that the antibody fragments distribute out of the vascular compartment but do not fully occupy the extracellular space. Our estimates of the latter, using thiocyanate as a marker, ranged from 220 to 327 mL kg-1 (rabbits and guinea-pigs, respectively). The distribution of Fab fragments in these two species differs significantly from that in the rat, where our earlier studies have shown that these antibody fragments are confined to the intravascular compartment with a distribution volume approximately equivalent to that of plasma (about 40 mL kg-1). PMID- 2576051 TI - Brain tyrosine increases after treating with prodrugs: comparison with tyrosine. AB - After mice had been treated with L-tyrosine, O-phospho-L-tyrosine, L-tyrosine methyl ester or N-acetyl-L-tyrosine, tyrosine was assayed by HPLC coupled with fluorometric detection. O-Phospho-L-tyrosine behaved as a tyrosine prodrug after its hydrolysis by acid and alkaline phosphatases. After the intraperitoneal administration of O-phospho-L-tyrosine or the methyl ester, there was a substantial increase in bioavailability in terms of the effect of tyrosine. The two prodrugs were as powerful as tyrosine following oral administration. N-Acetyl L-tyrosine was the least effective prodrug tested. The stability, solubility and bioavailability of O-phospho-L-tyrosine are consistent with proposing it for use as a tyrosine prodrug. In addition, it can be used parenterally. The use of a tyrosine aminotransferase inhibitor is necessary for limiting the hepatic breakdown of tyrosine and for increasing its bioavailability. PMID- 2576052 TI - Factors in snake venoms that increase capillary permeability. AB - Capillary permeability increasing (CPI) activity is a phenomenon of the microvasculature caused by many agents such as snake venoms, histamine, 5 hydroxytryptamine (5-HT), prostaglandins and leukotrienes. Since no systematic study has been done to determine what components of snake venom cause CPI activity, a CPI factor from Naja naja atra (Taiwan cobra) venom was isolated using intravenous injections of Evan's blue dye as the indicator of increased permeability and the factor's properties were extensively studied. Cardiotoxin from Naja naja kaouthia (Thailand cobra) and Mojave toxin from Crotalus scutulatus scutulatus (Mojave rattlesnake) venoms demonstrated CPI activity. Postsynaptic neurotoxins from an elapid and a hydrophid and myotoxin a from Crotalus viridis viridis (prairie rattlesnake) showed no CPI activity at the dose studied. The purified CPI active component from Naja naja atra venom was found to have cardiotoxic activity. Therefore, Elapidae cardiotoxins are CPI active factors. However, CPI activity is not due to cardiotoxins alone as the presynaptic neurotoxin, Mojave toxin, also showed CPI activity. Selective inhibitors were used to indicate possible mechanisms of action on the capillaries by Naja naja atra venom and Crotalus scutulatus scutulatus venom. The histamine H1-receptor blockers diphenhydramine, promethazine, and cyproheptadine were effective against both venoms in preventing increased capillary permeability. These results suggested that histamine release activity is the most likely mechanism resulting in CPI activity from these venoms. PMID- 2576053 TI - Transport of cephalosporin antibiotics in rat renal basolateral membranes. AB - Transport mechanisms of cephalosporin antibiotics in rat renal basolateral membranes have been studied in isolated membrane vesicles. Uptake of [14C]p aminohippurate, a typical organic anion, by basolateral membrane vesicles was enhanced when membrane vesicles were preloaded with unlabelled p-aminohippurate (counter-transport). Cephalosporins such as cephradine, cephalexin, and cefazolin inhibited the counter-transport of [14C]p-aminohippurate, as did unlabelled p aminohippurate and probenecid. In contrast, cephalexin did not affect the uptake of [3H]tetraethylammonium, an organic cation, by basolateral membrane vesicles. These results suggest that most cephalosporins are transported via organic anion transport systems in rat renal basolateral membranes. PMID- 2576054 TI - Vascular effects of propofol: smooth muscle relaxation in isolated veins and arteries. AB - Isolated hepatic portal veins and aorta taken from the rat were used to investigate the direct action of the intravenous anaesthetic propofol. This compound is known to produce a fall in blood pressure in man and animals and it has been suggested that the hypotension may result from a direct vasodilator action on the veins and arterioles. In our experiments propofol caused a dose related decrease of potassium-induced tone in both types of blood vessel. However, the concentrations required to produce this effect in the experiments on veins were significantly lower than those required to produce similar changes in the isolated artery preparation. We conclude that this direct action may contribute towards the hypotensive effects of propofol. PMID- 2576055 TI - Effectiveness of insulin suppositories in diabetic patients. AB - Experimental insulin suppositories regulated postprandial hyperglycaemia in diabetic patients. The insulin suppositories seemed also to avoid hyperinsulinaemia. The formulation with more rapid dissolution of insulin, which contained a solid dispersed form of insulin, effectively reduced the insulin dose required. PMID- 2576056 TI - Vasocontractile action of daunorubicin. AB - Daunorubicin (35.5-142 mumol L-1) induced in rat aortic strips a contraction with slow onset and a gradual development of tension on which neither phentolamine nor bromophenacyl bromide pretreatment had an effect. The contraction was not altered by removal of the endothelium but it was suppressed in calcium-free solution or by preincubation with nifedipine. These results suggest that daunorubicin directly stimulates vascular smooth muscle and induces a contractile response which is mainly dependent upon extracellular calcium. PMID- 2576057 TI - The systemic availability of buprenorphine administered by nasal spray. AB - The kinetics and systemic bioavailability of intranasally administered buprenorphine have been investigated in 9 healthy volunteers in an intranasal/intravenous cross-over study. Each subject received a nominal 0.3 mg dose of buprenorphine intranasally followed one week later by a matched dose intravenously. For the intranasal administration mean tmax and mean Cmax were 30.6 min and 1.77 ng mL-1, respectively. Mean intranasal bioavailability was 48.2 +/- 8.35% (mean +/- s.e.m.) of the intravenous value. Intranasal administration may represent a valuable new delivery route for buprenorphine. PMID- 2576058 TI - Decreased 5-hydroxytryptamine turnover in striatum and other brain regions after administration of 5-methoxy-3-(di-n-propylamino)chroman to rats. AB - 5-Methoxy-3-(di-n-propylamino)chroman (5-MeO-DPAC) caused a dose-dependent decrease in the accumulation of 5-hydroxytryptophan after decarboxylase inhibition in rat striatum, hippocampus and frontal cortex. The decreased 5 hydroxytryptamine (5-HT) turnover may have resulted from activation of 5-HT receptors on cell bodies of 5-HT neurons that project to the striatum and other brain regions, since 5-MeO-DPAC had earlier been reported to lack affinity for striatal binding sites. PMID- 2576059 TI - The effect of monoamine depletors on metrazol induced convulsions and brain gamma aminobutyric acid (GABA) contents in rats. AB - The thresholds for metrazol (pentylenetetrazol) clonic convulsions and brain gamma-aminobutyric acid contents were significantly reduced after treatment with the monoamine depletors reserpine, tetrabenazine and p-chlorophenylalanine. Moreover, alpha-methyltyrosine, and alpha-methyl-m-tyrosine also lowered metrazol threshold seizures, but had no effect on brain alpha-aminobutyric acid contents. Furthermore, neither 5-hydroxytryptophan nor tranylcypromine had a significant effect on metrazol threshold seizures or brain alpha-aminobutyric acid contents, but blocked the changes previously induced by p-chlorophenyl alanine and reserpine. PMID- 2576061 TI - [Determination of small intestinal transit time in beagle dogs using salicylazosulfapyridine]. AB - The method for the assessment of small intestinal transit time (SITT) in beagle dogs was investigated by using the time for the first appearance of sulfapyridine in the plasma (TFA) after oral administration of salicylazosulfapyridine (SASP). After administration of SASP into the small intestine or the cecum of anesthetized dogs, sulfapyridine (SP) was detected in the plasma only in the latter case. These results indicate that TFA could be an index of arrival time in the cecum, an index of SITT in dogs. A remarkable inter-individual variation of TFA was observed after oral administration of SASP to fasting dogs, and the mean value of TFA was about 3 h. As for intra-individual variation of TFA, both variable and less variable dogs were observed. TFA was prolonged significantly by atropine (0.1 mg/kg, i.v.) and shortened significantly by metoclopramide (0.5 mg/kg, i.v.). As the pharmacological modification of gastrointestinal motility was thus mirrored by TFA, SASP method is considered to be useful for the assessment of SITT in beagle dogs. PMID- 2576060 TI - [Selective and sensitive determination of an antiallergic agent, emedastine difumarate (KG-2413), in human plasma by the radioreceptor assay combined with a high-performance liquid chromatography]. AB - The selective and sensitive method for the determination of a new antiallergic agent, 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-1H-b enzimidazole difumarate (emedastine difumarate, KG-2413), in the human plasma has been developed. Emedastine was determined by the receptor assay after the separation from its metabolites by the use of high-performance liquid chromatography (HPLC). This combined method (HPLC-radioreceptor assay (RRA) method) allowed us the quantification only of 0.3 ng/ml of emedastine in the human plasma. The intra-assay coefficients of variation for the determination were below 12%. Furthermore, the total pharmacologically active metabolites, including unchanged emedastine, was determined by the extraction of the unconjugated metabolites in the human plasma with chloroform followed by the receptor assay (RRA method). The human plasma concentrations measured by the HPLC RRA method were in good agreement with those by the RRA method. These results suggested that in human pharmacological activities occurred by unchanged emedastine itself. PMID- 2576062 TI - Influence of the endothelium and alpha-adrenoreceptor antagonists on responses to noradrenaline in the rabbit basilar artery. AB - 1. Noradrenaline (10(-6)-10(-2) M) produced slow, concentration-dependent depolarization of smooth muscle cells in the rabbit basilar artery, which preceded the onset of contraction by around 8 s (n = 18). 2. With concentrations greater than 10(-4) M, noradrenaline produced action potentials and fast rhythmic depolarizations superimposed on the slow depolarization. Each fast event was followed by a clear increase in the rate of smooth muscle contraction. The selective alpha 1-adrenoreceptor agonist phenylephrine produced very similar membrane and contractile responses. 3. Action potentials were not produced in artery segments where the endothelium had been removed. In these segments, the amplitude of both contraction and slow depolarization to noradrenaline was similar to that observed in segments with an intact endothelium, but the tension increased more slowly; 84 s compared to the 52 s required to produce 50% of total contraction when the endothelium was functional. 4. The selective alpha 1 antagonist prazosin (10(-6) M) either abolished or significantly reduced both the slow depolarization (with concentrations less than 10(-3) M-noradrenaline) and smooth muscle contraction to noradrenaline. When prazosin was present, action potentials with 10(-3) M-noradrenaline were only produced in 50% of the cells studied. 5. Irreversible blockade of alpha-adrenoreceptors with benextramine (10( 5) M for 20 min) abolished action potentials and both the depolarization and contraction produced with all but the highest concentrations of noradrenaline. With 10(-3) M-noradrenaline, depolarization was produced but it was significantly reduced and usually not associated with smooth muscle contraction. 6. The results show that smooth muscle depolarization, contraction and possibly endothelium dependent action potentials are produced by alpha-adrenoreceptor stimulation. They also show that noradrenaline-induced action potentials produce smooth muscle contraction, and that slow depolarization is an important, but not absolute requirement for contraction. The fact that action potentials were produced in response to high concentrations of noradrenaline in the presence of prazosin, but not after benextramine, suggests that these concentrations of noradrenaline can surmount competitive antagonism with prazosin. PMID- 2576063 TI - The probability of quantal secretion at release sites in different calcium concentrations in toad (Bufo marinus) muscle. AB - 1. The number of quanta secreted from visualized release sites along terminal branches at toad (Bufo marinus) neuromuscular junctions in different extracellular concentrations of calcium ions. [Ca2+]o, and during facilitation was determined. Terminal branches were visualized by prior staining with the fluorescent dye, 3-3 diethyloxardicarbocyanine iodide (DiOC2(5)). 2. Increasing [Ca2+]o between 0.25 and 0.4 mM gave a similar proportional increase in the mean quantal content of the end-plate potential recorded with an extracellular electrode (me) at all sites along terminal branches. Thus the length constant for the experimental decline in me along terminal branches (the quantal length constant) remained constant with an increase in [Ca2+]o. The increase in m with [Ca2+]o followed a fourth power relation at both proximal and distal release sites. 3. The increase in me with [Ca2+]o was almost entirely due to an increase in the binomial probability for secretion, pe, which increased as the third to fourth power of [Ca2+]o. However, at higher [Ca2+]o there was an increasing tendency for the binomial parameter ne to increase. It is shown that when ne increases by about 1 there is very little change in pe, suggesting that the new release site recruited at high [Ca2+]o has a relatively low probability for secretion. 4. Test impulses gave a similar proportional increase in me following a conditioning impulse at all sites along terminal branches. The quantal length constant remained constant for both conditioning and test values of me. The increase in me for the test impulse increased linearly with an increase in me for the conditioning impulse at all release sites. 5. Facilitation of me declined exponentially with an increase in the test-conditioning interval. The time constant for this decline (30-40 ms) was similar at both proximal and distal release sites. Changes in facilitation of me were almost entirely due to changes in pe except at very short test-conditioning intervals of about 10 ms. At these intervals ne frequently increased by about 1 and there was very little change in pe. Again, this suggests that additional release sites recruited at short intervals have relatively low probability for secretion. 6. The results indicate that relatively low probability release sites exist in close juxtaposition to relatively high probability release sites which themselves decline in probability along the length of terminal branches. PMID- 2576064 TI - The probability of quantal secretion at release sites of different length in toad (Bufo marinus) muscle. AB - 1. The evoked quantal secretion recorded with an extracellular microelectrode (me) at selected sites along motor terminal branches visualized with the fluorescent dye 3-3 diethyloxardicarbocyanine iodide (DiOC2(5)) was compared with the maximum length of the synaptic contact at these release sites reconstructed from serial sections examined with the electron microscope. In addition the relationship between the binomial probability of secretion at release sites (pe) and the length of the synaptic contact was determined in an extracellular calcium. [Ca2+]o, of 0.35 mM. 2. Three of the six terminal branches studied in this way showed a decline in synaptic contact length of release sites from near the point of nerve entry (proximal) to the end of the branch (distal). The remaining three branches showed an increase in synaptic contact length near their middle, and in each case this was associated with a Schwann cell nucleus: contact length then declined to the end of the branches. 3. Both me and pe increased linearly with an increase in the maximum length of the synaptic contact over a range from 0.4 to 4.0 microns. This occurred independently of how the synaptic contact length varied along the length of terminal branches. The value of pe increased by about 0.05 for each 1 micron increase in synaptic contact length in a [Ca2+]o of 0.35 mM. 4. The decrease in synaptic contact length along the proximal parts of terminal branches, in which this occurs, is mostly due to a decrease in the length of close opposition (less than 0.2 micron) between the nerve terminal membrane and the postsynaptic membrane: the decrease in more distal parts of branches is due to the progressive encroachment of Schwann cell processes between the presynaptic and postsynaptic membranes as well as a decrease in synaptic contact length. PMID- 2576065 TI - Inhibitory interactions between motoneurone terminals in neonatal rat lumbrical muscle. AB - 1. Evoked synaptic potentials and currents were recorded in neonatal rat fourth deep lumbrical muscle during the period of polyneuronal innervation. Signs of inhibitory interactions between converging mononeurone terminals were detected. 2. Muscle fibres innervated by axons from the lateral plantar nerve (LPN) and from the sural nerve (SN) were studied. In unblocked preparations the muscle contracted, and electrode tips were mounted on flexible wires to prevent loss of impalements. 3. In voltage recordings from unblocked preparations, paired two shock stimulation of one nerve revealed synaptic depression: the second response was smaller than the first. When the two stimuli were delivered to different nerves (SN and LPN), the second response was smaller than its own control. 4. In voltage clamped, unblocked preparations, a similar result was obtained. Conditioning stimulation of one nerve (SN, for example) inhibited the response to test stimulation of the other nerve (LPN). The inhibition was greater with larger conditioning responses, was maximal when the conditioning and test stimuli were approximately superimposed, and decayed with a time course of several tens of milliseconds. Several tests showed that the end-plate was well clamped: the observed inhibition could not be explained by voltage escape at the end-plate. 5. The inhibition was not constant during the tail of the test end-plate current (EPC). Instead, it declined during the EPC tail, suggesting that the mechanism of inhibition was active, though diminishing, throughout the time course of the test EPC. 6. The amount of inhibition was not noticeably affected by altering the muscle membrane potential (two cells studied). 7. Treatment with curare or alpha bungarotoxin to block most ACh receptors reduced the inhibition. In about half of the fibres studied, no inhibition was evident: in the others, up to 50% inhibition was observed. The average inhibition for all receptor-blocked fibres was about 15%. 8. In six alpha-bungarotoxin-treated cells, multiple conditioning stimuli were delivered. In most cases, the amount of inhibition increased with increasing numbers of conditioning stimuli. 9. Several possible mechanisms of inhibition are discussed, including reduction of current through ACh channels during the test response owing to alterations in synaptic cleft ion concentrations produced by the conditioning response, presynaptic inhibition of transmitter release, and postsynaptic receptor saturation. PMID- 2576066 TI - Excitatory amino acid-receptor-mediated EPSPs in rat dorsolateral septal nucleus neurones in vitro. AB - 1. Intracellular recordings were made from rat dorsolateral septal nucleus (DLSN) neurones in vitro. We investigated depolarizations resulting from pressure application of excitatory amino acids and compared these to synaptically evoked excitatory postsynaptic potentials (EPSPs). 2. EPSPs evoked by focal fimbrial afferent stimulation in saline with 30-50 microM-bicuculline and 1.2 mM-Mg2+ yielded a linear amplitude-voltage relationship: their reversal potential was -3 mV. These EPSPs exhibited little sensitivity to 2-amino-5-phosphonopentanoate (APV), an N-methyl-D-aspartate(NMDA)-receptor-specific antagonist, but were markedly depressed by kynurenic acid, a broad-spectrum excitatory amino acid antagonist. 3. In Mg2(+)-free solution, the amplitude and the duration of EPSPs were increased markedly masking the following inhibitory postsynaptic potential (IPSP) and the late hyperpolarizing potential (LHP). These facilitated and broadened EPSPs were sensitive to APV or Mg2+. The APV or Mg2(+)-sensitive component of the EPSP obtained by digital subtraction suggests a slower time course for the NMDA-receptor-mediated EPSP compared to the non-NMDA-receptor mediated EPSP. On the other hand, in normal Mg2+ solution an EPSP evoked by either a single strong stimulus or by repetitive stimuli had APV-sensitive components. 4. The depolarizing potentials induced by pressure application of glutamate, kainate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), quisqualate or NMDA were compared. The amplitude-voltage relationship of depolarizations induced by NMDA obtained in a normal Mg2+ solution was non linear, but approached linearity when the same responses were recorded in a Mg2(+)-free solution. Depolarizations induced by kainate, AMPA and quisqualate were linear in their amplitude-voltage relationship in the presence or absence of Mg2+. APV blocked NMDA-induced depolarizations specifically, while kynurenic acid blocked all the depolarizations induced by NMDA, quisqualate, or kainate. 5. Our data demonstrate the existence of NMDA-receptor-mediated synaptic potentials in the rat DLSN, the characteristics of which are similar to those in other central nervous system regions. PMID- 2576067 TI - Bicuculline- and phaclofen-sensitive components of N-methyl-D-aspartate-induced hyperpolarizations in rat dorsolateral septal nucleus neurones. AB - 1. Intracellular recordings were made from rat dorsolateral septal nucleus (DLSN) neurones in vitro. Pressure application (puff) of N-methyl-D-aspartate (NMDA) usually produced a hyperpolarization followed by a depolarization in normal Mg2+ solution. 2. A hyperpolarizing response and a depolarizing response could be evoked separately by appropriate positioning of the puff pipette. The NMDA induced hyperpolarization was blocked by a low-Ca2+ solution or a tetrodotoxin (TTX)-containing solution, but under these conditions the NMDA-induced depolarization was spared. The amplitude of NMDA-induced hyperpolarizations was 7.7 +/- 2.7 mV (n = 13) at the resting membrane potential level. 3. An NMDA induced hyperpolarization had two components. A fast component reversed at about 76 mV and a slow component reversed at -90 mV. The reversal potential of the slow component shifted in the depolarizing direction of hyperpolarizing direction when the slice was bathed in a high or low-K+ solution, respectively. 4. The reversal potentials of NMDA-induced hyperpolarizations were similar to the synaptic potentials evoked by fimbrial stimulation. The reversal potentials of the fast and slow components were close to the IPSP reversal potential (-70 mV) and the late hyperpolarizing potential (LHP) reversal potential (-95 mV), respectively. 5. NMDA-induced hyperpolarizations were blocked by the specific NMDA receptor antagonist 2-amino-5-phosphonopontanoate (APV). The fast component of an NMDA induced hyperpolarization was blocked by the specific GABAA receptor antagonist, bicuculline, and the slow component was depressed by the specific GABAB receptor antagonist, phaclofen. 6. Glutamate receptor subtype-specific agonists, such as kainate or quisqualate, could induce similar hyperpolarizations which had bicuculline-sensitive and insensitive components. These non-NMDA-type agonist induced hyperpolarizations were not affected by APV (50 microM) but were blocked by kynurenic acid (1 mM). 7. We conclude that these excitatory amino acid-induced hyperpolarizations observed in the rat DLSN are mediated by GABAergic interneurones which have both non-NMDA-type and NMDA-type receptors. PMID- 2576068 TI - Dependence of spontaneous release at frog junctions on synaptic strength, external calcium and terminal length. AB - 1. The calcium dependence of spontaneous transmitter release from nerve terminals of different lengths was examined at neuromuscular junctions in frog muscle. Miniature endplate potential (MEPP) frequency was positively correlated with the endplate potential (EPP) quantal content and was dependent on external Ca2+. The higher the resting MEPP frequency in a 0.25 mM-Ca2+ Ringer solution, the greater the dependence on external Ca2+. MEPP frequency in all terminals dropped to approximately the same low level in a Ca2(+)-free Ringer solution containing EGTA. This suggests that terminals with higher release levels have a larger Ca2+ influx at rest. 2. Several tests were done to try to characterize the mode of Ca2+ entry into resting terminals. omega-Conotoxin (omega-CgTx) blocked evoked release and reduced MEPP frequency, but not as effectively as zero Ca2(+)-EGTA Ringer solution. Some component of Ca2+ influx thus appears to enter through channels insensitive to omega-CgTx. Tetrodotoxin (TTX) did not affect MEPP frequency, indicating that the Ca2+ did not enter through TTX-sensitive Na+ channels that might be opening spontaneously at rest. Hyperpolarization of the terminal by reducing the K+ in the Ringer solution caused no consistent differences in MEPP frequency, suggesting that the Ca2+ influx is relatively insensitive to small changes in membrane potential around the resting level. Strong buffering of the Ringer solution with citrate, to overwhelm any differences in Ca2+ buffering within different junctional clefts, had no significant effect on the MEPP frequency. 3. Evidence that the Na(+)-Ca2+ exchanger helps set the internal Ca2+ level was obtained. Reduction of the Na+ concentration in the Ringer solution caused increases in MEPP frequency ranging from 6 to 440%. However, these changes were not correlated with resting MEPP frequency, hence differences in MEPP frequency probably are not the result of differences in Na(+)-Ca2+ exchanger function in terminals having a uniform Ca2+ leak. 4. Although MEPP frequency was generally correlated with quantal content, in subsets of junctions grouped according to their similar quantal contents, there was a positive correlation between MEPP frequency and terminal length. 5. In zero Ca2(+)-EGTA Ringer solution, the low residual MEPP frequency is independent of terminal length, even when MPP frequency is sharply increased by tetanic stimulation. PMID- 2576069 TI - Participation of the kallikrein-kinin-receptor system in reflexes arising from neural afferents in the dog epicardium. AB - 1. Reflexogenic effects of bradykinin, lysyl-bradykinin and endogenously formed kinins on neural afferents of the left ventricular epicardium were studied in anaesthetized, open-chest dogs. 2. Epicardial application of either bradykinin (0.01-10 micrograms), lysyl-bradykinin (0.01-10 micrograms) or tissue kallikrein (0.003-1 U) consistently resulted in dose-related increases in blood pressure and heart rate. The pressor and heart rate responses to epicardial kallikrein were slower in onset and longer lasting than those evoked by bradykinin or lysyl bradykinin. The effects of kallikrein, but not those of exogenous kinins, were subject to tachyphylaxis. The application of higher doses of kallikrein (0.1 or 1 U) also resulted in long-lasting desensitization of the epicardium to the effects of bradykinin. 3. Treatment of the epicardium with a proteinase inhibitor, aprotinin, prevented the reflexogenic effects of kallikrein but not those of bradykinin or lysyl-bradykinin. Treatment with aprotinin also counteracted post kallikrein desensitization of sensory receptors of the ventricular epicardium to the reflexogenic effect of bradykinin. 4. Superfusion of the epicardium with a selective B2 receptor antagonist, D-Arg[Hyp3,Thi5,8,D-Phe7]-bradykinin, was equally effective in antagonizing the reflexogenic effects of kallikrein, bradykinin and lysyl-bradykinin. 5. We conclude that the response to epicardial application of kallikrein indicates an ample presence of endogenous substrate for local formation of bradykinin and/or related kinins. These then initiate reflex activation of the cardiovascular system by interacting with specific B2 receptors associated with sympathetic afferent neurones in the dog epicardium. We suggest that the kallikrein-kinin-receptor system has a role in the reflex function of the cardiac sympathetic afferents in both physiological and pathological conditions. PMID- 2576071 TI - Inhibition of acid formation and stimulation of somatostatin release by cholecystokinin-related peptides in rabbit gastric glands. AB - 1. The purpose of the present study was to investigate the role of somatostatin in the inhibition of acid production induced by caerulein and cholecystokinin (CCK) in isolated rabbit gastric glands. Acid production was estimated by the aminopyrine technique. 2. Exogenous somatostatin 14 and somatostatin 28 (10(-7) M) reduced to a similar extent the aminopyrine uptake produced by 5 x 10(-5) M histamine during the course of 40 min incubation. 3. Significant inhibition of histamine-stimulated aminopyrine accumulation occurred at a somatostatin 14 concentration of 10(-9) M. 4. Caerulein and CCK octapeptide (10(-13)-10(-7) M) were found to release somatostatin from isolated gastric glands in a dose dependent manner. The dose-response relationships for somatostatin release and inhibition of aminopyrine uptake were similar. Thus, the half-maximal dose approximations for somatostatin release and inhibition of aminopyrine uptake were 0.5 and 1.4 x 10(-9) M respectively for CCK octapeptide and 0.9 and 2.5 x 10(-11) M for caerulein. Heptadecapeptide gastrin proved to be a very poor releaser of somatostatin in the system used. The CCK octapeptide-induced somatostatin release was time dependent and the concentrations of somatostatin that accumulated in the incubation medium were similar to those of exogenous somatostatin that were needed to evoke inhibition. 5. The present results support the concept that cholecystokinin inhibits gastric acid secretion by releasing somatostatin from endocrine-like cells in the gastric mucosa. It is suggested that cholecystokinin related peptides may play a physiological role in inhibiting gastric acid secretion. A similar role for gastrin is not supported by the present study. PMID- 2576072 TI - [Mesenteric hematoma disclosing periarteritis nodosa. Apropos of a case]. AB - A 59 year old woman, asthmatic and hypertensive, presented with unexplained abdominal pains and signs of internal hemorrhage. Ultrasonography and CT demonstrated mesenteric hematomas. Theses hematomas had been related to fissured aneurysms of branches of superior mesenteric artery in course of polyarteritis nodosa and proved by angiography. PMID- 2576070 TI - Further observations on the behaviour of ouabain-insensitive sodium efflux towards proctolin in barnacle muscle fibres. AB - 1. A further study has been made of the stimulatory action of proctolin on the ouabain-insensitive Na+ efflux in single muscle fibres from the barnacle, Balanus nubilus. 2. (i) Strontium (Sr2+) behaves as a substitute for external Ca2+. In this case, however, the response to proctolin fails to decay. (ii) Injection of Sr2+ stimulates the ouabain-insensitive Na+ efflux. This effect is mimicked by injecting Ca2+. 3. Depolarization of the fibre membrane with 30 and 100 mM external K+ augments the response to proctolin. 4. Pre-injection of GTP or Gpp(NH)p (sodium 5-guanylylimidodiphosphate) prevents the response to proctolin from completely decaying. 5. Pre-injection of guanine nucleotides in conjunction with membrane depolarization stops the response to proctolin from decaying. 6. Measurements of Em before and during treatment with proctolin indicate a prompt but small and reversible fall in the membrane potential. 7. (i) The aequorin response of fibres pre-treated with ouabain to proctolin is monophasic or multiphasic, and concentration dependent, the minimal effective concentration being in the nanomolar range. (ii) The duration of these signals is usually less than 5 min; this is about half the time it takes for the stimulated Na+ efflux to reach a maximum. (iii) The aequorin response to proctolin occurs quite often in fibres suspended in nominally Ca2(+)-free artificial sea water. (iv) Sudden graded elevations in external K+ following complete decay of the aequorin response to proctolin are rapidly followed by stepwise transitory increments in light emission. (v) The aequorin response to 100 mM-external K+ is frequently a triplet. 8. (i) Together, these results are in line with the view that the action of proctolin on the ouabain-insensitive Na+ efflux is the result of a temporary fall in internal pCa and that its point of action is the Ca2+ channel, where a putative G protein in the presence of GTP or Gpp(NH)p is able to maintain constancy of the hormonal effect. (ii). They strengthen the argument that the barnacle muscle fibre as a preparation is especially suitable for studies of this kind. PMID- 2576073 TI - The benzodiazepine withdrawal syndrome and its management. AB - The literature on benzodiazepine dependence and withdrawal is reviewed with an emphasis on social and psychological considerations. The problems of when to prescribe, identifying withdrawal symptoms, effective communication with the patient, the structure of withdrawal programmes, and the use of drugs, psychological approaches and other services are discussed. PMID- 2576074 TI - The health of general practitioners: a cause for concern? PMID- 2576076 TI - [Clinical significance of glycylprolyl dipeptidyl-amino peptidase analysis in biochemical laboratory tests]. PMID- 2576075 TI - [Clinical significance of blood total testosterone and free testosterone analysis in endocrine tests of the gonadal and placental system]. PMID- 2576078 TI - [Significance of urinary alanine aminopeptidase analysis in clinical tests]. PMID- 2576077 TI - [Clinical significance of gamma-glutamyl transpeptidase analysis in biochemical laboratory tests]. PMID- 2576079 TI - [Significance of urinary gamma-glutamyltranspeptidase analysis in clinical tests]. PMID- 2576080 TI - [Significance of formiminoglutamic acid analysis in clinical tests]. PMID- 2576081 TI - Relationships between the effects of peripherally administered salmon calcitonin on calcaemia and brain biogenic amines. AB - The effects of s.c. administered salmon calcitonin on the biogenic amine neurotransmitters and metabolites were studied in discrete brain sections in order to evaluate the relationships between these central effects and the fall of serum calcium and to investigate the mechanisms of calcitonin-induced behavioral changes. The biogenic amines and metabolites were simultaneously determined by high-performance liquid chromatography with electrochemical detection in tissue samples obtained from rats treated with 10-80 MRC U/kg of the peptide. Some rats were pretreated with calcium lactate to inhibit the calcitonin-induced hypocalcaemia. Most of the effects, consisting of signs of serotonergic system activation, have been observed in the hypothalamus, accounting for some behavioral effects of the peripherally administered salmon calcitonin. It was speculated that the activation of the brain serotonergic system could result from two indirect and separate mechanisms: the first, which would involve enhanced serotonin synthesis, seemed to be facilitated by calcium availability. A second possible mechanism, which would involve enhanced serotonin release from the neurons, seemed to be mediated by the fall of calcium levels in the blood. PMID- 2576082 TI - Behavioral analysis of zopiclone on the basis of their discriminative stimulus properties in the rat. AB - Zopiclone is a new cyclopyrrolone derivative which exerts pharmacological activities similar to those of benzodiazepines in behavioral and biochemical studies. In order to clarify the discriminative stimulus properties of zopiclone, 8 rats were trained to discriminate the interoceptive stimulus induced by zopiclone (3.2 mg/kg, i.p.) from those of saline. Following discrimination acquisition, administration of zopiclone resulted in drug-appropriate responding with an ED50 of 1.3 (1.0-1.8) mg/kg. The zopiclone discriminative stimulus generalized to the benzodiazepines diazepam (1.8 mg/kg), nitrazepam (10 mg/kg) and alprazolam (10 mg/kg). A non-benzodiazepine, suriclone, at 3.2 mg/kg, generalized to the zopiclone stimulus in 5 out of 7 rats, but meprobamate, hydroxyzine, tracazolate and muscimol did not. The benzodiazepine antagonist Ro 15-1788 (1 mg/kg) completely blocked zopiclone stimulus. In contrast, however, bicuculline and pentetrazol failed to antagonize it. The serotonin antagonist cinanserin and ritanserin neither generalized to the zopiclone stimulus nor did they exhibit antagonism. These results suggest that the zopiclone discriminative stimulus is mediated by binding to benzodiazepine receptors and appears not to be related to GABAergic or serotonergic system. PMID- 2576083 TI - Heterogeneity of beta-adrenoceptor in canine veins: comparison among the facial, portal and saphenous veins. AB - A study was made on the characteristics of beta-adrenoceptors in the isolated canine facial, portal and saphenous veins. Ring segments of the facial and saphenous veins and longitudinal strips of the portal vein were suspended in tissue baths containing Krebs solution oxygenated and maintained at 37 degrees C. They were moderately contracted with prostaglandin F2 alpha before examining their relaxation responses. The facial and saphenous veins fully relaxed to isoproterenol, while the portal vein relaxed to a small extent (20% of maximum relaxation) even in the presence of an alpha-adrenoceptor blockade. In contrast, both forskolin, a direct activator of adenylate cyclase, and membrane-permeable dibutyryl cyclic AMP similarly relaxed all the veins studied. Thus, the reduction of coupling between beta-adrenoceptors and the adenylate cyclase system may be involved in the decreased responsiveness of the portal vein to beta-adrenoceptor agonists. In addition, analyses of beta-adrenoceptor agonism and antagonism, using selective (beta 1: T-1583, beta 2: procaterol) and non-selective (isoproterenol) agonists as well as selective (beta 1: atenolol, beta 2: ICI 118,551) and non-selective (propranolol) antagonists, confirmed that beta adrenoceptors in the canine facial vein are not homogeneous, with the beta 1 subtype predominating over the beta 2-subtype, and that the canine saphenous vein has a homogeneous population of the beta 2-subtype, as reported in the other species. PMID- 2576084 TI - Effects of clenbuterol on resting tension and contractile response in vesicourethral smooth muscle of rabbits. AB - The effects of clenbuterol, a selective beta 2-agonist, on isolated smooth muscle preparations from the rabbit bladder body, bladder base and proximal urethra have been investigated. The inhibitory effects on resting tension and acetylcholine- and field stimulation-induced contractions in the bladder body were compared with those of flavoxate, atropine, and verapamil. Clenbuterol (10(-10)-10(-7) M) had a strong, concentration-dependent relaxant effect on resting tension of the bladder body, and the relaxant effect was antagonized by propranolol. However, clenbuterol had little effect on the bladder base or proximal urethra. Isoproterenol, a non-selective beta agonist, gave a similar result, but was less potent than clenbuterol. Flavoxate failed to reduce the resting tension, but rather enhanced the spontaneous rhythmic contraction in a concentration-dependent manner. Atropine had little effect. Verapamil produced a concentration-dependent relaxation in the bladder body. Acetylcholine-induced contraction in the bladder body was completely inhibited by pretreatment with atropine (10(-7) M). Clenbuterol, flavoxate, and verapamil concentration-dependently inhibited acetylcholine-induced contraction. Field stimulation-induced contraction in the bladder body was not completely inhibited by atropine. However, the residual contraction was completely inhibited by tetrodotoxin. Clenbuterol, flavoxate, and verapamil concentration-dependently inhibited field stimulation-induced contraction. The inhibitory effects of clenbuterol and verapamil were antagonized by an application of propranolol and an increase in external Ca, respectively. The data suggest that the selective relaxant effect of clenbuterol on the bladder body is due to beta 2-antagonistic action, resulting in the inhibition of the contractile response to acetylcholine or field stimulation. Also, its response was different from that of the other drugs used. PMID- 2576085 TI - Effect of alpha 2-adrenergic receptor antagonist (midaglizole) on gastrointestinal motility in conscious dogs. AB - To clarify the physiological role of the mechanism that adrenergic nerve inhibits Ach release from intramural cholinergic nerve endings, the influence of Midaglizole, alpha 2-adrenergic receptor antagonist, to postprandial gastrointestinal motilities in conscious dogs was investigated. Postprandial motilities of gastric antrum, duodenum, ileum, and colon were significantly enhanced by Midaglizole (3.0-5.0 mg/kg body weight, i.v.). These excitatory responses were abolished by atropine (0.05-0.1 mg/kg body weight, i.v.). On the other hand, in most cases (29 cases out of 32), when Midaglizole was administered during quiesent phase of IMC, no change occurred in gastrointestinal motility. However, after subliminal dose of pentagastrin or cisapride, which stimulated Ach release from intramural cholinergic neuron without development of motility, was administered, Midaglizole induced phasic, postprandial motility-like contraction in gastrointestinal tract. Even in the fasted state, when Midaglizole was administered intragastrically, irregular contractions with high amplitude occurred in every regions from gastric antrum to colon. And these excitatory responses were abolished by atropine. Similar reaction was observed also in truncal vagotomized dogs. These results suggest that it is the physiological mechanism that adrenergic nerve presynaptically inhibits Ach release from intramural cholinergic neuron, which is the main mechanism of development of postprandial motility, acting on alpha 2-adrenergic receptor, and has tonic control of postprandial motility. PMID- 2576086 TI - [Anti-cholinesterase activity of dopamine D2 receptor antagonist: its clinical significance]. AB - Anti-cholinesterase activity of dopamine D2 receptor antagonist, domperidone was studied by means of chronically implanted force transducers in the gastrointestinal (GI) tract in five conscious dogs. Cisapride was used as a drug to stimulate endogenous release of acetylcholine. In the digestive state, cisapride (0.25 mg/kg) stimulated 18.6 +/- 5.6% increase in the motor index of the gastric antrum alone, however, combined administration with domperidone (1.0 mg/kg-hr) significantly enhanced the motor index in the gastric antrum and duodenum. In the gastric antrum, the increase was 68.1 +/- 7.2%. During the interdigestive state, cisapride did not always induce the interdigestive migrating contractions (IMC)-like contractions in the GI tract, but the background infusion of domperidone significantly increased the incidence of the occurrence of IMC-like contractions by cisapride. In in vitro study, weak but significant anti-cholinesterase activity was found in domperidone, the activity being about 1/1,000 of that of neostigmine. In dog experiment, similar enhancement of motor stimulating activity of cisapride was observed when neostigmine was given at 1.0 micrograms/kg-hr. In conclusion, domperidone has anti-cholinesterase activity and acts to enhance motor stimulating activity of cisapride through inhibition of cholinesterase activity in the upper digestive tract. PMID- 2576087 TI - Deficient oxidation of trihydroxycoprostanic acid in liver homogenates from patients with peroxisomal diseases. AB - The activation of palmitate and trihydroxycoprostanic acid and the peroxisomal oxidation of palmitate, trihydroxycoprostanic acid and their CoA esters were measured in homogenates prepared from fresh liver tissue of patients undergoing hepatic surgery and from frozen postmortem liver specimens of controls, patients with Zellweger syndrome and a patient with pseudo-Zellweger syndrome, a deficiency of peroxisomal 3-oxoacyl-CoA thiolase. In contrast to the findings in control livers, peroxisomal beta-oxidation of palmitate and of palmitoyl-CoA was severely impaired, and oxidation of trihydroxycoprostanic acid and its CoA ester could not be detected in the livers of the patients affected by peroxisomal diseases. The finding in this paper, that the oxidation of trihydroxycoprostanoyl CoA can be measured reliably in small amounts of human liver, will be of valuable help in the differential diagnosis and classification of peroxisomal disorders and will help to elucidate the exact nature of some of the defects present in these disorders. PMID- 2576088 TI - [The somatostatin analog: current and future perspectives]. PMID- 2576089 TI - [DNA polymorphisms as implant markers in allogeneic bone marrow transplantation. Preliminary evaluation]. AB - After allogeneic bone marrow transplantation (BMT), patient hematopoietic and lymphoid cells are replaced by cells derived from the donor marrow. To document and characterize successful engraftment, host and donor cells must be distinguished from each other. We have used DNA sequence polymorphism analysis in 6 patients, at times varying, to determine reliably the host or donor origin of posttransplant cell populations and to compare these results with those obtained using red blood cell antigens and cytogenetics. Initially full engraftment was documented in all patients. In 1 patient a mixed lymphohematopoietic chimerism was documented 6 months after BMT and it reverted to donor hematopoiesis at 1 year post BMT. Posttransplant leukemic relapse was studied in two patients and shown to be of host origin in both cases. The DNA restriction fragment length polymorphisms (RFLP), are a powerful tool for the documentation of engraftment after BMT, to document mixed lymphohematopoietic chimerism and for the evaluation of leukemic relapse. PMID- 2576090 TI - Reactivity of Haemophilus influenzae type b anti-pili antibodies. AB - The reactivity of anti-pilus antibodies to native and denatured Haemophilus influenzae b (Hib) pili was studied using rabbit serum prepared against piliated H. influenzae b strain M43 (p+) and adsorbed with its non-piliated variant, strain M42 (p-). The specificity of the adsorbed serum for Hib pili was documented by immunogold electron microscopy and by immunoprecipitation, which revealed the 24 kDa pilin band from strain M43 (p+) that was not seen on strain M42 (p-). In immunodot assays, the anti-pilus antibodies reacted with the native pili present on the outer membrane of strain M43 (p+), but on Western blot assay using denatured outer membranes, the anti-pilus antibodies did not react with the 24 kDa pilin subunit. These data demonstrate that the anti-pilus antibodies in the adsorbed serum recognize conformational epitopes that depend on the tertiary or quaternary structure of Hib pili. PMID- 2576091 TI - The toxin-coregulated pilus (TCP) of Vibrio cholerae: molecular cloning of genes involved in pilus biosynthesis and evaluation of TCP as a protective antigen in the infant mouse model. AB - A serum containing antibodies to non-lipopolysaccharide (non-LPS) protective antigens of Vibrio cholerae has been used, after extensive absorption, to facilitate the cloning of genes involved in the synthesis of toxin-coregulated pili (TCP). A gene bank was constructed from V. cholerae Z17561 DNA using a mobilizable cosmid vector in Escherichia coli, and subsequently transferred by conjugation into V. cholerae O17. This strain does not produce TCP in vitro and lacks non-LPS protective antigens. Eight positive clones were isolated, and of these, four produced TCP as determined by electron microscopic and immunoblotting analyses. TCP-positive O17 clones were 70-fold more virulent than TCP-negative clones or O17 in the infant mouse cholera model. Only the former could remove protective antibodies from the clone-probing serum by absorption. As a corollary, serum containing antibodies to TCP protected mice from challenge with TCP positive clones, but not with TCP-negative clones or O17. Our data indicate that TCP can function as both a virulence determinant and a protective antigen in the infant mouse model. PMID- 2576092 TI - DNA fingerprints from hypervariable mitochondrial genotypes. AB - Conventional surveys of restriction-fragment polymorphisms in mitochondrial DNA of menhaden fish (Brevoortia tyrannus/patronus complex) and chuckwalla lizards (Sauromalus obesus) revealed exceptionally high levels of genetic variation, attributable to differences in mtDNA size as well as in restriction sites. The observed probabilities that any two randomly drawn individuals differed detectably in mtDNA genotype were 0.998 and 0.983 in the two species, respectively. Thus, the variable gel profiles provided unique mtDNA "fingerprints" for most conspecific animals assayed. mtDNA fingerprints differ from nuclear DNA fingerprints in several empirical respects and should find special application in the genetic assessment of maternity. PMID- 2576093 TI - Variances of the average numbers of nucleotide substitutions within and between populations. AB - Statistical methods for computing the variances of nucleotide diversity within populations and of nucleotide divergence between populations are developed. Both variances are computed by finding the phylogenetic relationships of the DNA sequences studied through the unweighted pair-group method or some other tree making method. The methods developed are applicable to both DNA sequence and restriction-site map data. PMID- 2576094 TI - Genes for biosynthesis and assembly of CS3 pili of CFA/II enterotoxigenic Escherichia coli: novel regulation of pilus production by bypassing an amber codon. AB - The complete nucleotide sequence of the 4746bp HindIII fragment encoding the genes for the biosynthesis and assembly of CS3 pili has been determined. By site directed mutagenesis in conjunction with analysis of the plasmid-encoded proteins in minicells, the actual reading frames for the various products have been determined. This demonstrated that the genes for four of the proteins (63 kD, 48 kD, 33 kD, and 20 kD in size) are encoded entirely within the same open reading frame as a fifth protein (104 kD). However, for synthesis of this latter protein, suppression or readthrough of an internal amber codon is required. Termination at this codon is also necessary for synthesis of the former proteins. Two further proteins are also encoded within the HindIII fragment: a 27 kD precursor of a periplasmic protein and the 17.5kD precursor of the major CS3 fimbrial subunit. PMID- 2576095 TI - Analysis of genes coding for the sialic acid-binding adhesin and two other minor fimbrial subunits of the S-fimbrial adhesin determinant of Escherichia coli. AB - The S fimbrial adhesin (Sfa) enables Escherichia coli to attach to sialic acid containing receptor molecules of eukaryotic cells. As previously reported, the genetic determinant coding for the Sfa of an E. coli O6 strain was cloned, the gene coding for the major fimbrial subunit was identified and sequenced and the S specific adhesin was detected. Here we present evidence that in addition to the major subunit protein SfaA three other minor subunit proteins, SfaG (17 kD), SfaS (14 kD) and SfaH (31 kD) can be isolated from the S-specific fimbrial adhesin complex. The genes coding for these minor subunits were identified, mutagenized separately and sequenced. Using haemagglutination tests, electron-microscopy and quantitative ELISA assays with monoclonal anti-SfaA and anti-SfaS antibodies the functions of the minor subunits were determined. It was determined that SfaS is identical to the S-specific adhesin, which also plays a role in determination of the degree of fimbriation of the cell. The minor subunit SfaH also had some influence on the level of fimbriation of the cell, while SfaG is necessary for full expression of S-specific binding. It was further shown that the amino terminal protein sequence of the isolated SfaS protein was identical to the protein sequence calculated from the DNA sequence of the sfaS gene locus. PMID- 2576096 TI - Diversity of the outer membrane protein P2 gene from major clones of Haemophilus influenzae type b. AB - In previous studies, it has been demonstrated that outer membrane protein P2 from Haemophilus influenzae type b has porin activity and that antibody directed against P2 is protective in an infant rat bacteraemic model. Outer membrane protein subtyping has been employed to subclassify type b Haemophilus isolates. Strain MinnA has the outer membrane protein subtype 1H and is representative of the dominant clonal group of disease-producing isolates in the United States. In the present study, the P2 gene from strain MinnA was employed to probe EcoRI- and Pvull-digested chromosomal DNA from 24 Haemophilus influenzae type b isolates representative of the common outer membrane protein subtype groups observed throughout the world. Restriction fragment length polymorphisms were identified for the members of the outer membrane protein subtype 3L group, but not for the other subtypes examined. The P2 gene from each of four prototype isolates was then cloned, sequenced and compared to the previously reported sequence of the strain MinnA gene. The P2 gene from each of two isolates with the outer membrane protein subtype 3L was identical to the MinnA P2 sequence. The P2 gene from a subtype 2L isolate differed by a single nucleotide and the gene from a subtype 6U isolate differed by 13 nucleotides. Thus, the P2 protein is highly conserved among type b isolates. PMID- 2576097 TI - [Intensification of the growth and development of Bacillus thuringiensis H14 266/2-1 by optimizing the nutrient medium]. AB - The mathematical method of experimental design was used to develop a new enzymic medium for cultivation of Bacillus thuringiensis H14 266/2-1, a bactoculicide producer. The optimized medium based on corn flour enzyme lysate as a carbon source and fodder yeast enzyme lysate as a source of nitrogen amine made it possible to increase twice the titre biomass yield for 24 h cultivation as compared to the initial medium. The above medium does not yield to the initial production medium in the insecticide activity. PMID- 2576098 TI - Health for all children by the year 2000. PMID- 2576099 TI - [Treatment of schizophrenia from the viewpoint of the patient. Studies on the course of treatment and neuroleptic treatment from a personal perspective]. PMID- 2576100 TI - B-waves in healthy persons. AB - The objective of this study was to determine, whether 0.5-2/min oscillations in intracranial pressure ('B-waves') are a physiological phenomenon. In a group of 5 patients 0.5-2/min oscillations of ventricular pressure simultaneous with oscillations in the middle cerebral artery (MCA) flow velocity, as assessed by transcranial Doppler sonography, were observed. Similar oscillations in MCA blood flow velocity were demonstrated in 8 out of 10 healthy subjects with an amplitude of about 10% of the mean flow velocity. We speculate that oscillations both in ventricular pressure and middle cerebral artery blood flow velocity are caused by rhythmic diameter changes of cerebral vessels with concomitant cerebral blood volume oscillations. Our data support the suggestion that B-waves may be physiological. PMID- 2576101 TI - Single pulse pressure wave analysis by fast Fourier transformation. AB - Pressure recordings from 16 patients with normal pressure by hydrocephalus were analysed during controlled intracranial hypertension. Single pulse pressure wave (PPW) analyses were performed on a computer system with programs for automatic computation of mean intracranial pressure (MICP), pulse amplitude (PA), rise time coefficients (RT) and fast Fourier transformation (FFT). We found good correlation between the first harmony, MICP and PA, and between the fifth harmony and RT. The PPW is mainly composed of low-frequency components, but with increasing RT more high-frequency components are present. RT changes as compliance of the brain changes. Therefore the high-frequency components of the FFT may predict changes in the cerebral compliance, although there was no correlation between any of the harmonies and the pressure volume index (PVI). In this investigation PVI was found difficult to perform and evaluate. PMID- 2576102 TI - Intracranial pressure changes following primate subarachnoid haemorrhage. AB - In 29 anaesthetized baboons avulsion of a small intracranial artery was used to produce a subarachnoid haemorrhage, in a closed-skull situation. Intracranial pressure was measured by extradural transducers, and arterial pressure was also measured continuously, with periodic measurements of cerebral blood flow. After haemorrhage there was an immediate fall in cerebral perfusion pressure in nearly all cases, reaching zero in 9 animals. In 18 there was a significant pressor response in the systemic circulation, but perfusion pressure usually remained low in spite of this response. Perfusion pressure recovered after a few minutes in most cases. In the 19 cases where intracranial pressure was measured on both sides, differences occurred in 11, with the higher pressure always on the same side as the haemorrhage. The difference was evident very soon after haemorrhage in 9 cases, and lasted over half an hour in 5 of them. The mechanism of arrest of bleeding was, in most of this series, not that of a zero perfusion pressure. Explanations for this and for the occurrence of differential pressures are discussed. PMID- 2576103 TI - Observations on cerebral ischaemia in cats at injury threshold levels. AB - The potential for recovery of brain tissue subjected to ischaemia at a threshold level of injury was evaluated in cats subjected to 20 min middle cerebral artery occlusion. In addition to assessment of regional cerebral blood flow and water content, the permeability of the bloodbrain barrier and morphological changes detected by light microscopy were studied at various time intervals. Our observations revealed that although a similar reduction of blood flow during arterial occlusion was found both in the caudate nucleus and the cerebral cortex, the reactive hyperaemia was consistently higher in the caudate nucleus than in the cortex. After 24 h the caudate nucleus also revealed a significantly higher water content and increased vascular permeability than the cortex. Morphological observations at 24 h in areas affected by ischaemia showed widespread, marked ischaemic neuronal injury, whereas at 3 d there was, in addition, a vigorous proliferative reaction of vascular elements. Cats sacrificed at 14 d revealed a remarkably good preservation of neurons, both in the caudate nucleus and cortex which otherwise showed a few circumscribed, small, infarcts surrounded by normal nerve cells. Our study suggests that neurons injured at threshold level have a considerable capacity for recovery. Otherwise, with a similar degree of ischaemia, the caudate nucleus appears more prone to increased vascular permeability and oedema than the cerebral cortex. PMID- 2576104 TI - Oxygen-free radicals in traumatic brain oedema. AB - Oxygen-free radicals have been implicated as causative factors in ischaemic and traumatic processes. Oxygen-free radical scavengers can be used potentially to treat brain oedema. We investigated the effects of superoxide dismutase and dimethylthiourea on brain oedema. Vasogenic brain oedema was produced in 44 cats by a cortical freezing lesion. Animals were separated into three groups: (1) cold induced oedema with sacrifice at 6, 24 and 48 h; (2) cold-induced oedema with sacrifice at 6, 24 and 48 h: subgroup A was pretreated with 10,000 u./kg polyethylene glycol and superoxide dismutase; subgroup B received a bolus injection of free superoxide dismutase (4 mg/kg) and then 1 mg/kg/min for 20 min; (3) cold-induced oedema with sacrifice at 6 and 24 h: this group was pretreated with 500 mg/kg dimethylthiourea. Brain water content was measured by the specific gravity method. Detection of superoxide radicals was carried out by the direct cortical application of nitroblue tetrazolium. Free and polyethylene glycol superoxide dismutase did not prevent the development of brain oedema, but superoxide radicals were detected in the cold lesion. Dimethylthiourea prevented the development of brain oedema in the white matter adjacent to the lesion at 6 h but not at 24 h. These findings indicate that oxygen-free radicals are generated by the brain following cold injury and the demonstration of these radicals offers an important clue in the genesis of traumatic brain oedema. PMID- 2576105 TI - Natural and surgically imposed anastomoses of the circle of Willis. AB - The efficacy of the circle of Willis as a flow equalizer is well known. Most cerebral macrovasculatures also contain other natural anastomoses which are activated in times of stenotic stress. For the past several decades, neurosurgeons have surgically augmented the cerebral network with additional vessels which further increase the flow of blood to a defrauded region of the brain. It is desirable to know quantitatively what role these anastomoses play in the delivery of blood. Apart from computer simulation, such knowledge remains out of reach to the medical community but with modern simulation techniques, a wealth of information can be made available. This paper presents both time-dependent and period-averaged results of a detailed study of cerebral anastomoses. Four different models of the macrovasculature in the circle of Willis vicinity have been developed, two of which contain an extracranial-intracranial (EC-IC) anastomosis. Five cases were developed to show how the amount of blood flow is related to the sizes of the anastomoses. Since the EC-IC bypass is only marginally beneficial in those patients whose cerebral circulations are well equipped with naturally occurring anastomotic vessels, procedures should be developed to screen for their presence or absence. The fluid mechanics associated with the EC-IC bypass operation dictate a beneficial result. Since the surgical procedures fail to consistently show reduction in risk even when good grafts have been made, there is an enigma in the study group results. PMID- 2576106 TI - Neurotrophic effect of cholecystokinin on ventral spinal cord in culture. AB - Studies of the effect of cholecystokinin on organotypic cultures of rat ventral spinal cord revealed that concentrations of 10(-4) to 10(-14) M exert a marked growth-stimulating effect. In the presence of cholecystokinin, the neuritic extension of the ventral spinal cord exceeds control values 3.5-6.5 times. The growth zone of spinal cord explants increases in cholecystokinin-treated cultures. The possible mechanism of the trophic effect of cholecystokinin on the ventral spinal cord is discussed briefly. PMID- 2576107 TI - Analysis of neural dynamics and memory organization. AB - We analysed neural network dynamics by a Caianiello type of equation with special reference to memory organization and the corresponding synaptic connection matrix. Global analysis of the dynamics yielded only stable equilibrium configurations and no periodic solutions. PMID- 2576108 TI - Congenital lumbosacral lesions with late onset in adult life. AB - Seven adult patients with congenital lumbosacral lesions and clinical onset in adult life are reported. All also had an abnormally low and tethered spinal cord. A thickened filum terminale and a spinal lipoma are the most common lesions in adults, whereas others, including diastematomyelia, fibrous adhesions, previous meningocele repair and dermal sinus are more rare. Although water-soluble myelography visualizes the abnormally low conus well and may diagnose a diastematomyelia and a thickened filum, computerized tomography, CT myelography and magnetic resonance may provide a better diagnostic definition of the other abnormalities. Surgical treatment should be performed in all adult patients with progressive symptoms. Transection of the thickened filum or of fibrous adhesions and the removal of a spinal lipoma, diastematomyelia septum or dermal sinus tract, result in remission of the pain and improvement of the sensorimotor deficits, or at least prevent the progression of the neurological troubles. PMID- 2576109 TI - Analysis of reruptured cerebral aneurysms and the prophylactic effects of barbiturate therapy on the early stage. AB - During the past seven years, we have studied 661 cases of ruptured intracranial aneurysms. Rebleeding occurred in 65 cases (10%) and, within this group, 43 cases (70%) rebled within the first 6 hours after initial subarachnoid haemorrhage (SAH). Analysis of these 43 cases led to the following conclusions: 22 patients incurred rebleeding from causes such as transfer (6 cases), neuroradiological examinations (13 cases), and tracheal intubation during anaesthesia etc. (3 cases), while no special causative factors were discovered in the other 21 cases. Rebleeding occurred in 19 patients even while on absolute bed rest and in 11 patients who had induced systemic arterial hypotension (under 140 mmHg) through treatment. Six cases experienced rebleeding while undergoing angiography within 6 hours after the first subarachnoid haemorrhage. Eight of 17 reruptured anterior cerebral complex (Acom) aneurysm cases and 8 of 11 reruptured middle cerebral artery (MCA) aneurysm cases had an intracerebral haematoma on initial CT-scan following the first attack, demonstrating that the risk of rebleeding was very high in cases of intracerebral haematoma. The mortality rate for these rebleeding cases was high i.e. 65%. Therefore, because the time factor could precipitate rebleeding, early transfer and operation was considered optimal for minimizing rebleeding soon after an aneurysm rupture, even though angiography within 6 hours of the first SAH was a serious risk. Barbiturate therapy, performed as early as possible for serious cases, was considered to be effective in preventing rebleeding. PMID- 2576110 TI - Fructose-added glycerol (Glyceol) for therapy of elevated intracranial pressure: analysis of the side effects of long-term administration in a multi-institutional trial. AB - The effects of long-term administration of fructose-added glycerol solution (Glyceol): 10% glycerol, 5% fructose, 0.9% sodium chloride; 600-2000 ml/d intravenously for 7-63 d) were evaluated in a multi-institutional trial involving 1346 cases. Improvement of the neurological signs and symptoms of elevated intracranial pressure was recognized by responsible physicians in close association with the administration of Glyceol (75.1%). The intracranial pressure measured directly also decreased in most cases following the administration of Glyceol (81.2%). No significant changes were observed in serum electrolytes and osmolarity at the end of the long-term administration. Unfavourable changes in clinical conditions which were considered very likely or suspected to be due to the long-term administration of Glyceol were recorded in 2 cases (0.1%) or 13 cases (1.0%), respectively. Most of these changes were abnormalities of serum electrolytes. It appeared, however, that the abnormalities of serum electrolytes may be readily correctable, and rarely induced if standard care of the serum water-electrolyte balance is carried out and unless too large doses are employed. Other changes appeared to be related more to preexistent complications and/or the administration of other drugs, rather than to the administration of Glyceol alone. Thus, administration of Glyceol appeared feasible for the therapy of elevated intracranial pressure over the long term. PMID- 2576111 TI - Effects of a high molecular weight toxin from Physalia physalis on glutamate responses. AB - The effects of a high molecular weight toxin from Physalia physalis (P3) were investigated on glutamate evoked potentials in snail (Zachrysia guanesis) neurons and in crayfish (Cambarus clarkii) neuromuscular junction. The glutamate evoked potentials of snail neurons were reversibly blocked by P3 in a dose-dependent manner (2-200 microM). A reversible blocking action was also found for P3 on excitatory junctional potentials and on glutamate potentials of crayfish at a concentration range of 6 nM-60 microM. Experiments carried out with independent stimulation of the excitatory and inhibitory nerves showed that the effect of P3 (60 nM-10 microM) was exerted predominantly on excitatory junctional potentials. However, at higher doses (greater than 10 microM) a slight reduction of the inhibitory potentials was also observed. These results suggest that P3 reversibly blocks glutamate receptors. Thus, it could be a promising tool for further studies on glutamatergic transmission. PMID- 2576112 TI - Excitatory amino acids mediate responses elicited in vitro by stimulation of cortical afferents to reticularis thalami neurons of the rat. AB - The effects of the excitatory amino acids on the nucleus reticularis thalami were examined by intracellular recordings from rat thalamic slices. Non-N-methyl-D aspartate receptor agonists and glutamate induced a membrane depolarization and a reduction in input resistance, while N-methyl-D-aspartate and aspartate induced a prolonged discharge, which in some neurons took the form of a burst firing associated with an apparent increase in membrane input resistance. Both the N methyl-D-aspartate and the aspartate effects were blocked by D-2-amino-5 phosphonovalerate, while the effects of glutamate, kainate and quisqualate were not. The excitatory postsynaptic potential evoked by corticothalamic fiber stimulation shows two components: an early, short-lasting, 2-amino-5 phosphonovalerate-insensitive portion, and a late, 2-amino-5-phosphonovalerate sensitive decay phase. It is suggested that glutamate acts in nucleus reticularis thalami cells preferentially on the non-N-methyl-D-aspartate receptors, while aspartate shows an N-methyl-D-aspartate-like effect. The two excitatory amino acids glutamate and aspartate play a determinant role in the modulation of thalamic activity driven by corticothalamic projection. PMID- 2576113 TI - Bilateral tectal projection of single nigrostriatal dopamine cells in the rat. AB - Employing fluorescent retrograde double/triple labeling techniques, we found that a substantial population of substantia nigra pars reticulata cells send divergent axon collaterals to both the ipsilateral striatum and bilateral superior colliculi in the rat. These multi-collateralized neurons were localized predominantly in the ventrolateral portion of the substantia nigra pars reticulata at its rostral level. Furthermore, tyrosine hydroxylase immunofluorescence histochemistry combined with fluorescent retrograde tracing techniques showed that the vast majority (more than 85%) of such specifically branched cells are dopaminergic. This novel nigral cell population seems to be in a strategic position to evoke dopamine-mediated motor impairments (i.e. abnormal saccadic eye movements in Parkinsonism) and/or behavioral syndromes (i.e. compulsive turning behavior) through the GABA-containing nigrotectal pathway. PMID- 2576114 TI - [Clinical evaluation of the use of somatostatin (VAL 787) in the treatment of upper digestive hemorrhage]. AB - Personal experience with 30 patients treated with Somatostatin for upper gastrointestinal bleeding is reported. The conclusion is drawn that this drug, reducing chloro-peptic secretion and hepatic portal blood flow, can reduce and control bleeding and postpone the surgical operation, which has a high rate of mortality. PMID- 2576115 TI - [The effect of beta blockers on the QT interval: the possible role of mechanisms other than beta block]. AB - The authors evaluated QT interval changes after 7 and 14 days of treatment with 3 different betablockers--acebutolol, atenolol and penbutolol--in 3 groups of hypertensive patients. Acebutolol (400 mg u.i.d.) prolonged QTc interval in a statistically significant fashion, atenolol (100 mg u.i.d.) induced a significant and constant reduction, whereas QTc interval was shortened by penbutolol only after the first week, shifting toward pretreatment values during the second week. The physiological correlation between QT and RR was slightly modified by acebutolol and penbutolol, but markedly reduced after atenolol. Such differences might be of importance in clinical practice because are likely to be linked to different mechanisms intrinsic to each agent. PMID- 2576117 TI - [Takayasu's arteritis. The report of a clinical case]. AB - The etiopathogenic features and noninvasive diagnosis of Takayasu's arteritis are reviewed in brief and the case of a young man suffering from the disease (type I in Ueno's classification) is reported. PMID- 2576116 TI - [Takayasu's disease. A review of the literature. A study of a familial case of Takayasu's arteritis and the possible associations with type-1 diabetes mellitus]. AB - After a brief review of the literature on Takayasu's disease with particular emphasis on its relationship with the HLA system, the case of a mother and daughter both suffering from Takayasu's type systemic arteritis is presented with particular reference to a possible association with type-I diabetes mellitus (IDDM) in the light of the patient's HLA typing results. PMID- 2576118 TI - Pupil response: a psychophysiological measure of fear during analogue desensitization. AB - 15 highly aroused snake phobics individually constructed fear hierarchies by selecting colored photographs of snakes. Subjects either imagined fear scenes based on their photographs or were exposed to duplicate projected slides during desensitization. Pupillary responses of the Slide Group were also recorded before, during, and after desensitization. Fear of snakes was significantly reduced for both groups within five or fewer desensitization sessions. Changes in pupil size of the Slide Group appear to reflect arousal of fear as well as reduction of fear after treatment. Current technology makes pupillary response a viable psychophysiological measure of fear. PMID- 2576119 TI - Evidence for a respiration-modulated cholinergic action on the activity of medullary respiration-related neurons in the rabbit. An iontophoretic study. AB - Effects of the iontophoretically administered cholinergic agonists acetylcholine, bethanechol and DMPP on the activity of medullary respiration-related neurons were examined in urethane-anaesthetized rabbits. Inhibitory effects prevailed over excitatory effects. Analysis of cholinergic effects by cycle-triggered averaging revealed three major types of neuronal responses: (i) constant alterations of spike-density throughout the whole period of activity ("constant effects"), (ii) effects increasing during the progression of the burst of discharge or effects restricted to a particular fraction of the burst ("phasic effects") and (iii) effects which were characterized by an excitation during one respiratory phase and an inhibition during the other phase ("bi-phasic effects"). The latter type of effects was observed in phase-spanning respiration-related neurons. Phasic effects were mainly observed in inspiration-related neurons which were predominantly inhibited by stimulation of muscarinic receptors. Inspiratory R beta-neurons in no case were phasically affected by cholinergic agents. The mean muscarinic inhibition of inspiration-related neurons increased with the progression of inspiration. The mean nicotinic inhibition of expiration-related neurons decreased with the progression of expiration. Results suggest that the efficacy of (i) a central inspiration terminating mechanism and (ii) the onset of discharge of expiratory neurons is modulated by acetylcholine. PMID- 2576121 TI - Shifts in the voltage dependence of synaptic release due to changes in the extracellular calcium concentration at nerve terminals on muscle of crayfish and frogs. AB - The rate of release of transmitter quanta, elicited by variable depolarization pulses applied to a nerve terminal by means of a macro-patch-clamp electrode, was measured in muscles of crayfish and frogs. The electrode was perfused with solutions containing different Ca concentrations, Cae. The bath was superfused separately, usually with solutions containing nominally no Cab and elevated Mgb. A fixed depolarization pulse followed the variable test pulse within 7-10 ms, and facilitation, Fc, of release after the fixed pulse was determined as a measure of Ca-inflow during the test pulse. As described before, Fc always showed a peak, Fc, at depolarization amplitudes of the test pulse below the saturation level of release. When Cae was changed, the depolarization levels generating Fc shifted in a negative direction if Cae was lowered, and in a positive direction if Cae was increased. These shifts agreed with the known dependence of the effective membrane potential (controlling e.g. Ca inward current) on Cae which is due to shielding of surface changes by Ca2+ (cf. Hille 1984). Changes of Cab, at constant Cae, did not affect the depolarization dependence of Fc. It is concluded that Ca inflow is not the only factor controlling quantal release, and that at least in depolarizations beyond those eliciting Fc another potential dependent factor increases release while Ca inflow presumably falls. PMID- 2576120 TI - Calcium dependence of quantal release triggered by graded depolarization pulses to nerve terminals on crayfish and frog muscle. AB - Quantal transmitter release was measured in small portions of neuromuscular junctions by means of a perfused macro-patch-clamp electrode. Release was elicited by graded current pulses through the recording electrode (excitation blocked by TTX). On increasing the stimulation current from a threshold amplitude, release rose steeply for several orders of magnitude and finally approached a saturation level of about 10 quanta/pulse. Reduction of the Ca concentration in the perfusate of the electrode, Cae, depressed the saturation level of release relatively little and had practically no effect on the threshold current amplitude, as long as the Ca concentration in the superfusion of the bath, Cab, remained high. When Cab was reduced too, the depression of release was more severe. The dependence of release on Cae was determined for a large range of Cae for saturating depolarization pulses. In crayfish, at 0 Cab, in double logarithmic release-Cae plots the maximum slope was on average 3.9, and this slope dropped to on average 2.1 in 13.5 mM Cab. In frog, at 0 Cab, the respective double-logarithmic slope was 3.5, while in 1.8 mM Cab this slope declined dramatically, the rate of release decreasing on average only by a factor of 3.8 from 10 mM to 0.02 mM Cae. These results are interpreted by the assumption that the resting Ca concentration in the terminal, Cair, has strong influence on the rate of release due to depolarization pulses in low Cae, and that Cab has control on Cair in the terminal. PMID- 2576122 TI - Calcium and depolarization dependence of twin-pulse facilitation of synaptic release at nerve terminals of crayfish and frog muscle. AB - Transmitter quanta were elicited from nerve terminals of crayfish and frog muscle by depolarization pulses through a macro-patch-clamp electrode. The rates of quantal release for twin pulses and their ratio, twin pulse facilitation, Fd, were determined. When the electrode was perfused with normal Cae (13.5 mM for crayfish, 1.8 mM for frog), Fd was low for threshold depolarizations, increased to a maximum at medium depolarizations, decreased when the rate of release due to the first pulse approached saturation, and increased again for larger depolarizations. If under these conditions the superfusion of the muscle outside the electrode was changed from normal to 0 Cab and high Mgb solution, Fd increased. When the Ca concentration around the terminal, Cae, was reduced to levels at which release did not reach the saturation level for large depolarizations, Fd in dependence on depolarization did not show the minimum at higher depolarizations. The amplitude of Fd measured for large, constant depolarization pulses showed a maximum at a Cae below that of the normal solution. The maximum of Fd was much higher if the superfusion of the bath contained 0 Cab and high Mgb than when normal bathing solution was superfused. The maxima of Fd at a low value of Ca inflow are predicted by the "residual Ca" theory of facilitation, if release is influenced by a resting low internal Ca concentration, Cair, and reaches a saturation level for large Ca-inflow. It is also predicted that decreasing Cair (as in low Cab) will increase Fd. PMID- 2576124 TI - Comparative studies of somatostatin-14 and some of its fragments on passive avoidance behavior, open field activity and on barrel rotation phenomenon in rats. AB - Behavioral effects of somatostatin-14, and some of its fragments [somatostatin(3 8), somatostatin(9-14), somatostatin(7-10)] after intracerebroventricular (ICV) administration have been investigated in male rats. In a passive avoidance learning test, somatostatin-14 (0.6 nM) given immediately after the learning session increased the avoidance latency at 24 hr after the injection, when compared to a somatostatin(3-8) (0.6 nM)-treated group. However, compared to a saline-treated group, the peptides did not significantly influence the avoidance latency. Somatostatin-14 administered in higher dose (6.0 nM) decreased the avoidance latency compared to the saline-treated group, while its fragments did not influence it. In an open field behavioral test, immediately after the 24-hr passive avoidance test, 6 nM of somatostatin-14 decreased the rearing activity, while the fragments did not influence this behavior. Somatostatin-14 produced barrel rotation in a dose-related manner, but after the injection of a high dose of the peptide (12 nM) all of the animals died in cardiorespiratory failure (apnea, pulmonary oedema). The fragments did not produce barrel rotation. PMID- 2576123 TI - Twin pulse facilitation in dependence on pulse duration and calcium concentration at motor nerve terminals of crayfish and frogs. AB - Phasic release from motor-nerve terminals of crayfish and frogs was elicited and recorded by means of a macro-patch-clamp electrode through which the terminal was depolarized in graded pulses. The tip of the electrode was perfused and the Ca concentration around the terminal, Cae, was controlled independent from that in the superfusion of the muscle, Cab. Release increased with pulse duration with a double-logarithmic slope of 5 to 9 in crayfish and frogs, which represents a form of "early facilitation" (Katz and Miledi 1968). In crayfish, this relation was shifted to longer pulse durations on lowering Cae, while in frogs, in addition, the saturation level of release was suppressed at low Cae. Responses to twin pulses with intervals of 7-10 ms showed facilitation, Fd. When pulse duration of the twin pulses was increased, starting from about 0.5 ms, Fd increased to a maximum, but declined for longer pulses which elicited release approaching the saturation range. On lowering Cae, the maximum of Fd, Fd, increased in amplitude and was shifted to larger pulse durations. Also reduction of Cab increased Fd. The effects of pulse duration and of Cae and Cab on Fd are predicted by the residual Ca theory of facilitation, if it is assumed that changes of Cae produce corresponding changes in Ca inflow during depolarization, and if the resting intracellular Ca concentration is influenced by the extracellular Ca concentration. The large values of early facilitation can not be explained by the residual Ca theory of facilitation and may indicate the action of another depolarization dependent factor which joins in the control of release. PMID- 2576126 TI - Effects of corticotropin-releasing factor (CRF), tuftsin and dermorphin on behavior of squirrel monkeys maintained by different events. AB - The effects of intracerebroventricular (ICV) administration of ovine CRF (0.1 30.0 micrograms/kg), dermorphin (0.3-30.0 micrograms/kg) and tuftsin (10-3000 micrograms/kg) were examined in squirrel monkeys trained to respond under a multiple 3-min fixed-interval schedule of food presentation and either shock presentation or stimulus-shock termination. Initial administration of the 41 amino acid polypeptide CRF increased food-maintained responding by 150-200% in 2 of 3 subjects. However, no other doses tested affected response rates, a result that may have been due to the rapid development of tolerance. The tetrapeptide tuftsin selectively increased responding maintained by food presentation at doses that decreased shock-maintained responding. The heptapeptide dermorphin selectively increased food-maintained responding when responding in the other component of the multiple schedule was maintained by shock presentation. When responding was maintained by a multiple food, stimulus-shock termination schedule, dermorphin decreased response rates in both components. Dermorphin's rate increases were blocked by the opiate antagonist naloxone, indicating that dermorphin's actions were mediated through the opiate receptor. These results indicate that the behavioral effects of tuftsin, dermorphin, and perhaps CRF, depend on the manner in which responding is controlled by its consequences. While the actions of tuftsin and dermorphin are believed to be mediated through the opiate system, the behavioral effects observed in primates appear different from the effects of morphine under similar schedule conditions. PMID- 2576125 TI - Developmental expression of corticotropin releasing hormone messenger RNA and peptide in rat hypothalamus. AB - We have examined corticotropin releasing hormone (CRH), arginine vasopressin (AVP) and somatostatin (SOM) mRNA expression and peptide content in the rat hypothalamus from day 20 of fetal life (F20) to the fifteenth day of postnatal life (P15). During this time, hypothalamic CRH mRNA levels did not change significantly, whereas there was a gradual six-fold rise in CRH peptide levels. AVP mRNA levels fell three-fold between F20 and P1 and increased six-fold between P1 and P15. AVP peptide levels increased three-fold, with most of the rise occurring between P1 and P15. From F20 to P15, SOM mRNA and peptide levels rose four- and eight-fold, respectively. The changes in the levels of these three hypothalamic gene products correlate with the previously described alterations in the responsiveness of the HPA axis observed in fetal and early postnatal rats, suggesting a role for these neuropeptides in the modulation of the HPA axis during this developmental period. PMID- 2576127 TI - Solitary hypothalamic neurons inherently express vasopressin and tyrosine hydroxylase. AB - Hypothalamic neurons were grown as single cells in three-dimensional culture. Solitary neurons lacking cell contacts were immunocytochemically examined for inherent expression of vasopressin (VP), tyrosine hydroxylase (TH), and luteinizing hormone releasing hormone (LHRH). Immunoreactive VP and TH were detected within a day. Sixty to eighty-five percent of neurons displayed homogeneously distributed reaction product for VP or TH. One percent exhibited intense punctate staining of somas and varicosities. Few neurons stained for LHRH. Results indicate that hypothalamic neurons can express appropriate neuropeptides and transmitter-specific products without contacting other neurons or nonneuronal cells. Thus, this culture system may provide a useful model to study intrinsic neuronal processes. PMID- 2576129 TI - Modern techniques of differentiating the various phenotypes of phenylketonuria. AB - Recognition of various phenylketonuria phenotypes has led to a variety of descriptive terms but classical phenylketonuria (PKU) may be defined as phenylalanine (PA) tolerance of 10-20 mg/kg/day at 5 years. The term 'mild PKU' indicates PA tolerance of 20-50 mg/kg/day whereas children with benign hyperphenylalaninaemia show normal development and are able to eliminate 100 mg/kg within 24 hours. The genetic basis for PKU has been investigated by reverse transcription via mRNA of the genes for phenylalanine hydroxylase (PH) present on chromosome 12q 22-24.1. The resulting complementary DNA sequence has been studied and the normal genes characterized. Following digestion of DNA from PKU patients and their families with restriction endonucleases, haplotype analysis has allowed identification of 12 restriction fragment length polymorphism haplotypes associated with normal and mutant PH alleles. Four haplotypes accounted for 91% of all mutant alleles in the Danish population studied. For heterozygotic parents it is possible to determine the haplotype associated with the normal allele and the mutant allele. Correlation between the different haplotypes and PKU phenotypes has allowed identification of the mutation responsible for classical PKU. Fifty eight per cent of mutant PKU alleles in the Danish population were found to be associated with 2 haplotypes and this is consistent with a founder effect in which the spread of mutant alleles passively follows the spread of these haplotypes in the European population. The phenotypical diversity of PH deficiency arises from multiple mutant alleles. Two mutations account for the majority of classical PKU in Denmark and since 75% of the Danish PKU population are heterozygotes for PH haplotypes, the various phenotypes reflect the composite activity and interactions of gene products from two mutant alleles. PMID- 2576128 TI - The metabolic neuropeptides of the corpus cardiacum from the potato beetle and the American cockroach are identical. AB - Two neuropeptides with adipokinetic activity in Locusta migratoria and hypertrehalosaemic activity in Periplaneta americana were purified by high performance liquid chromatography from the corpus cardiacum of the Colorado potato beetle, Leptinotarsa decemlineata. The sequences of both peptides, designated Led-CC-I and Led-CC-II, were determined by pulsed-liquid phase sequencing employing Edman degradation after deblocking enzymatically the N terminal pyroglutamate residue. The C-terminal of both peptides were blocked and neither molecule was cleaved by carboxypeptidase. Both peptides were found to be octapeptides; Led-CC-I has the primary structure pGlu-Val-Asn-Phe-Ser-Pro-Asn-Trp NH2, and Led-CC-II has the primary sequence pGlu-Leu-Thr-Phe-Thr-Pro-Asn-Trp-NH2. These structures are identical to the two hypertrehalosaemic hormones from the American cockroach. Preliminary experiments show that the synthetic peptides are apparently involved in the control of amino acid metabolism during flight of the potato beetle. PMID- 2576130 TI - Pharmacokinetics of sulfasalazine metabolites in rats following concomitant oral administration of riboflavin. AB - Sulfasalazine, 60 mg/kg, was administered orally to groups of rats (n = 4) along with 1, 5, or 10 mg/kg of riboflavin. Plasma and urine were assayed for 5 aminosalicylic acid, acetyl-5-aminosalicylic acid, sulfapyridine, and acetyl sulfapyridine using an HPLC method. The mean percent of dose recovered as total metabolites in urine was significantly greater (alpha = 0.01) for the group receiving 10 mg/kg riboflavin compared to the controls or the group receiving 1 mg/kg riboflavin. Plasma AUC and Cmax values were also significantly greater (alpha = 0.05) for the 10 mg/kg riboflavin group. These results suggest that at higher doses, a significant fraction of riboflavin reaches the colon intact and stimulates more efficient reduction of the azo bond in sulfasalazine. Since the concentrations of 5-ASA achieved in the colon may be directly related to the efficacy of sulfasalazine in treating inflammatory bowel disease, concomitant administration of riboflavin may enhance sulfasalazine's efficacy in humans. PMID- 2576131 TI - The SHR exhibits less "anxiety" but increased sensitivity to the anticonflict effect of clonidine compared to normotensive controls. AB - The behaviour of the adult (16 weeks) spontaneously hypertensive rat (SHR) was compared to that of age-matched normotensive Wistar (WISTAR) and Wistar-Kyoto (WKY) rats in two animal models of anxiety, Vogel's conflict test (VT) and Montgomery's conflict test (MT). With respect to "inborn anxiety", the three strains ranked differently in the two tests, WISTAR greater than WKY = SHR in the VT, but WKY greater than WISTAR greater than SHR in the MT. However, the SHR was the least "anxious" strain in both tests. The SHR also appeared more active and reactive than both the other strains. In the SHR and in the WKY, but not in the WISTAR, the alpha 2-adrenoceptor agonist clonidine in a narrow low dose-range produced anxiolytic-like effects of similar magnitudes. The SHR, however, responded in a ten-fold lower dose than did the WKY. The present findings, in conjunction with previous data, are not in all parts compatible with the locus ceruleus hypothesis of anxiety and may indicate that the anticonflict effect of clonidine is mediated through activation of postsynaptic alpha 2-adrenoceptors rather than of alpha 2-autoreceptors. PMID- 2576132 TI - [The hypophyseal-testicular system in cryptorchism patients following surgical treatment]. AB - The status of the hypophyseal-testicular system was studied in 80 patients at various time after operation to assess the results of surgical treatment of cryptorchidism. In patients operated on for unilateral cryptorchidism the level of FSH exceeded normal values in 23% of cases, LH--in 13%, the level of testosterone was lowered in 15%. In patients after orchiopexy for bilateral cryptorchidism a rise of the FSH level was 3-fold more frequent (78%), of the LH level--5-fold (64%) and the level of testosterone decreased 2-fold more frequently (34%). A conclusion is that in a majority of patients with bilateral cryptorchidism FSH and LH values do not return to normal in the postoperative period whereas in unilateral cryptorchidism they do not differ significantly from their normal values. The most severe hormonal disorders were noted in patients operated on at later time. Therefore it necessitates early surgical treatment of cryptorchidism. Severe hormonal disorders were usually combined with considerable changes in spermatogenesis, especially in patients with bilateral retention operated on in the post pubertal period. PMID- 2576133 TI - Three-dimensional structure of the neurotoxin ATX Ia from Anemonia sulcata in aqueous solution determined by nuclear magnetic resonance spectroscopy. AB - With the aid of 1H nuclear magnetic resonance (NMR) spectroscopy, the three dimensional structure in aqueous solution was determined for ATX Ia, which is a 46 residue polypeptide neurotoxin of the sea anemone Anemonia sulcata. The input for the structure calculations consisted of 263 distance constraints from nuclear Overhauser effects (NOE) and 76 vicinal coupling constants. For the structure calculation several new or ammended programs were used in a revised strategy consisting of five successive computational steps. First, the program HABAS was used for a complete search of all backbone and chi 1 conformations that are compatible with the intraresidual and sequential NMR constraints. Second, using the program DISMAN, we extended this approach to pentapeptides by extensive sampling of all conformations that are consistent with the local and medium-range NMR constraints. Both steps resulted in the definition of additional dihedral angle constraints and in stereospecific assignments for a number of beta methylene groups. In the next two steps DISMAN was used to obtain a group of eight conformers that contain no significant residual violations of the NMR constraints or van der Waals contacts. Finally, these structures were subjected to restrained energy refinement with a modified version of the molecular mechanics module of AMBER, which in addition to the energy force field includes potentials for the NOE distance constraints and the dihedral angle constraints. The average of the pairwise minimal RMS distances between the resulting refined conformers calculated for the well defined molecular core, which contains the backbone atoms of 35 residues and 20 interior side chains, is 1.5 +/- 0.3 A. This core is formed by a four-stranded beta-sheet connected by two well-defined loops, and there is an additional flexible loop consisting of the eleven residues 8-18. The core of the protein is stabilized by three disulfide bridges, which are surrounded by hydrophobic residues and shielded on one side by hydrophilic residues. PMID- 2576134 TI - MDMA transiently alters biogenic amines and metabolites in mouse brain and heart. AB - (+-)-3,4-Methylenedioxymethamphetamine (MDMA) (10, 20, and 40 mg/kg) was administered to male CF-1 mice which were sacrificed 3, 6, or 24 hours posttreatment for analysis of brain and cardiac biogenic amines and metabolites. In contrast to reported effects of MDMA in the rat, the highest dose of MDMA transiently elevated mouse brain 5-hydroxytryptamine (5-HT) 3 hours following drug treatment. Levels of dopamine were not significantly affected. 5 Hydroxyindoleacetic acid and dihydroxyphenylacetic acid were significantly lowered by MDMA at the two early time points. The highest dose of MDMA produced a transient depletion of norepinephrine in mouse brain and heart tissue. Only the effects of MDMA on cardiac norepinephrine were prevented by pretreatment of animals with desipramine. A regimen consisting of four daily doses of 40 mg/kg MDMA only produced significant declines in 5-HIAA, dopamine and homovanillic acid levels one week following the last dose. These data confirm previous reports that mice are resistant to the neurotoxic effects of MDMA suggesting that a species variation in response to MDMA exists. PMID- 2576135 TI - Isolation-induced social behavioral deficit test: effect of tranquilizing drugs. AB - Mice were reared in isolation for one week. Then, one isolated and one group reared mouse were observed together under an inverted beaker for two minutes. The number of escape attempts of the isolated mouse were half of those of the grouped mouse. This is considered as a social behavioral deficit. The present study was undertaken to assess the effect of neuroleptics and various anxiolytic agents on this behavioral deficit. Neither acute administration of chlorpromazine, levomepromazine, sulpiride, flupentixol, pipotiazine, pimozide and haloperidol nor the subchronic (5 days) administration of flupentixol, pipotiazine and pimozide impaired the behavioral deficit. Diazepam and triazolam increased, chlordiazepoxide, hydroxyzine and buspirone did not modify the behavioral deficit. It is concluded that neuroleptics and anxiolytic agents did not impair the isolation-induced social behavioral deficit either because of inadequate doses or duration of administration or because this behavioral state is unresponsive to neuroleptics and anxiolytic agents. PMID- 2576136 TI - Anxiolytic properties of 1-aminocyclopropanecarboxylic acid, a ligand at strychnine-insensitive glycine receptors. AB - The effects of 1-aminocyclopropanecarboxylic acid were investigated on performance in an elevated plus-maze. This compound is a high-affinity, partial agonist ligand at strychnine-insensitive glycine receptors of the N-methyl-D aspartate receptor complex. Like chlordiazepoxide, 1-aminocyclopropanecarboxylic acid increased in a dose-dependent manner both the percent entries into and the percent time spent in the open arms of the plus-maze. However, 1 aminocyclopropanecarboxylic acid was significantly less efficacious than chlordiazepoxide in these measures and increased, while chlordiazepoxide decreased, the time spent in the middle platform of the plus-maze. These findings indicate that ligands acting through strychnine-insensitive glycine receptors on the N-methyl-D-aspartate receptor complex may represent a new class of anxiolytic agents with a profile which differs from the benzodiazepines. PMID- 2576137 TI - Effect of YM-09151-2, a putative D2 dopamine receptor antagonist, on dopamine metabolism in the striatum of rats. AB - YM-09151-2, a novel benzamide derivative, significantly increased the concentrations of dopamine (DA) metabolites, both 3,4-dihydroxyphenylacetic acid and 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid). The maximum increase in such metabolites was about 4-fold the concentration in control animals, and was observed at 2 hr after oral administration. 3-Methoxy-4 hydroxyphenylethylene glycol, a metabolite of noradrenaline, was slightly increased in its concentration exhibiting a transient effect, but 5 hydroxyindoleacetic acid was not. YM-09151-2 antagonized the decreasing effects of apomorphine, a nonselective DA agonist, and LY-171555, a selective D2 DA receptor agonist, on the concentrations of DA metabolites in the brain. In contrast, SCH-23390, a selective D1 DA receptor antagonist, did not antagonize the effects of DA agonist. These results strongly suggest that YM-09151-2 is a selective antagonist of D2 DA receptor and a candidate as a new antipsychotic agent for clinical use. PMID- 2576138 TI - Serotonergic innervation of the rat caudate following a neonatal 6 hydroxydopamine lesion: an anatomical, biochemical and pharmacological study. AB - 6-Hydroxydopamine (6-OHDA) treatment of neonatal rats resulted in a dose-related loss of striatal dopamine (DA). These reductions corresponded closely with the loss of tyrosine hydroxylase-containing terminals at this brain site. Striatal serotonin (5-HT) concentration increased only after DA was maximally depleted by the highest dose of 6-OHDA. Quantitative immunohistochemistry revealed that the increased 5-HT content after neonatal 6-OHDA lesioning was due to a proliferation of 5-HT nerve terminals. The density of immunoreactive 5-HT-containing terminals appeared to increase more than did the 5-HT content. The present study examined whether 5-HT hyperinnervation was playing a role in behavioral responses induced by D1-DA agonists and antagonists in neonatally lesioned rats, because reports have suggested that these drugs may interact with 5-HT receptors. However, SCH 23390, the D1-DA antagonist (0.3 mg/kg), did not alter behavioral responses to 5 HTP and SKF-38393 (3 mg/kg), a D1-DA agonist did not produce any signs of activating 5-HT receptors in 5,7-DHT-lesioned rats. These data indicate that these compounds affecting D1-DA receptors do not have a significant effect on 5 HT function at doses which have maximal effects on D1-DA receptor function. Pretreatment with the 5-HT antagonist methysergide did not produce a change in apomorphine-induced locomotion and did not antagonize the self-mutilation or the other behaviors produced by L-DOPA or SKF-38393 in neonatally lesioned rats, suggesting that 5-HT hyperinnervation is not responsible for these drug-induced changes in neonatal 6-OHDA-lesioned rats. PMID- 2576139 TI - The antinociceptive effects of 3,4-methylenedioxymethamphetamine (MDMA) in the rat. AB - The antinociceptive effects of MDMA and morphine were examined in rats using the tail-flick and hot-plate analgesiometric tests. MDMA, in the dose range of 1.5 6.0 mg/kg IP, produced a dose-dependent elevation in hot-plate latency, but did not elevate tail-flick latency. In contrast, morphine (2-8 mg/kg, IP) produced analgesia on both the tail-flick and hot-plate tests in a dose-dependent manner. Neither the opiate antagonist naltrexone nor the adrenoceptor antagonist phentolamine effectively attenuated MDMA-induced analgesia. Conversely, the serotonin antagonist methysergide significantly reversed the analgesic effects of MDMA on the hot-plate test. These findings suggest that the antinociceptive effects of MDMA are serotonergically mediated. Furthermore, the results verify earlier findings describing the test-specific effects of serotonin-induced pain modulation. PMID- 2576140 TI - Mechanisms involved in the respiratory depressant actions of nicotine in anesthetized rats. AB - In the urethane-pentobarbital anesthetized rat, the respiratory depressant and lethal effects of intravenously infused (-)-nicotine (120 micrograms/kg/min) or (+)-nicotine (600 micrograms/kg/min) were effectively prevented by pretreatment with the opioid antagonist, naltrexone, whereas the lethal effect of (-)-nicotine (120 micrograms/kg/min) was not altered by bilateral adrenalectomy. Further, pretreatment with either the nicotinic ganglion-blocker, mecamylamine, a secondary amine, or the quarternary nicotinic ganglion-blocker, hexamethonium, completely prevented the lethal effects of (-)-nicotine (120 micrograms/kg/min). These data suggest that central opioidergic and nicotinic processes are involved in nicotine's respiratory depressant and lethal effects. PMID- 2576141 TI - Discriminative stimulus properties of CL218872 and chlordiazepoxide in the rat. AB - Rats were trained to discriminate either CL218872 (5 mg/kg PO) or chlordiazepoxide (5 mg/kg PO) from vehicle in a 2-lever discrimination task on an FR20 schedule. The discriminative cues produced by these two drugs generalised to a range of benzodiazepine receptor agonists and partial agonists. Nitrazepam, diazepam, RU32698 and RU32514 were less potent in substituting for the CL218872 cue than the chloridiazepoxide cue. Zopiclone, RU31719 and RU43028 substituted for both cues with similar potency, whilst zolpidem and CL218872 were clearly more potent in substituting for the CL218872 cue. Chlordiazepoxide substituted only partially for the CL218872 cue, even at doses which decreased the rate of responding. CGS9896 substituted partially for both cues, but was less effective with the CL218872 cue. RU39419 substituted for the chlordiazepoxide cue, but antagonised the CL218872 cue. CGS8216 and FG7142 antagonised both cues. The contributions of benzodiazepine receptor subtypes or partial agonism to the generation of the CL218872 cue is discussed. PMID- 2576142 TI - Lifetime antipsychotic-drug exposure, dyskinesia and related movement disorders in the developmentally disabled. AB - The relationship between dyskinesia and related movement disorders was examined as a function of cumulative exposure to antipsychotic drugs (APD). Lifetime drug exposure histories were obtained for 162 developmentally disabled (DD) persons; drug-exposed groups were compared to nondrug-exposed groups. There were no statistically significant relationships between dyskinesia and the amount of lifetime APD exposure, nor between dyskinesia and the number of long-term APDs, mean exposure, peak exposure, recency of exposure, duration of exposure, changes in medication levels, number of drug interruptions, age, gender, cerebral palsy, epilepsy, or IQ. Of the other movement disorders, a positive relationship was noted only between akathisia and long-term APD exposure; the increased prevalence of akathisia persisted beyond four years after APD withdrawal. PMID- 2576143 TI - The effects of ondansetron (GR38032F) in rats and mice treated subchronically with diazepam. AB - Using rat and mouse models of aversive behaviour, we have further investigated the properties of the 5-HT3 receptor antagonist ondansetron (GR38032F) that are relevant to its proposed use as an anxiolytic agent. Tolerance to the disinhibitory properties of diazepam was readily demonstrated in the social interaction test in the rat, but did not occur after subchronic treatment with ondansetron. In both the light/dark exploration test in mice and the social interaction test in rats, withdrawal from subchronic treatment with diazepam increased behavioural suppression, whereas this was not observed with ondansetron. The behavioural suppression and weight loss induced by either the withdrawal of diazepam or the administration of the benzodiazepine receptor antagonist, flumazenil, in animals treated subchronically with diazepam, was prevented or antagonised by diazepam or ondansetron. Buspirone was ineffective. It is concluded that, in rats and mice, tolerance to the disinhibitory effects of ondansetron does not occur, that withdrawal from subchronic treatment with ondansetron is not associated with any behavioural disturbances and that ondansetron is highly effective in preventing the behavioural suppression and weight loss following withdrawal from subchronic diazepam treatment. These data suggest that ondansetron may have major therapeutic advantages over currently available anxiolytic agents, particularly in patients who have previously received prolonged benzodiazepine therapy. PMID- 2576144 TI - Nicotine-induced tail-tremor and drug effects. AB - Tail-tremor induced by repeated and daily administration (0.5 mg/kg SC x 6 times/day) of nicotine as well as effects of various drugs on this response were investigated in Wistar strain male rats. Daily administration of nicotine in doses of 0.5 mg/kg SC caused tail-tremors to appear beginning on the 3rd day. Tail-tremor induced by the first injection of each day gradually increased with the daily injections, however, the heightened effect of this first injection at the beginning of each day decreased during the day upon repeated administration of 6 times/day at 2-hr intervals. Basically, tail-tremor appeared about 5 min after SC administration of nicotine and reached a peak approximately 7-9 min after injection, declining to zero afterwards. Different drugs showed various effects on this response. While mecamylamine (0.5 and 1.0 mg/kg IP) abolished nicotine-induced tail-tremor, arecoline (0.5 and 1.0 mg/kg IP), atropine (2.5 and 5.0 mg/kg IP), scopolamine (1.0 and 2.0 mg/kg IP) and hexamethonium (0.5 and 1.0 mg/kg IP) showed no such effects. Furthermore, physostigmine (0.1 mg/kg IP) actually potentiated this action. These results suggest that tail-tremor induced by nicotine may be mediated through central nicotine receptor system. PMID- 2576145 TI - Preferential stimulation of D1 or D2 receptors disrupts food-rewarded operant responding in rats. AB - Rats were trained to lever-press for food on a variable interval 30-sec schedule. Following stabilization of response rates, separate groups of rats were treated with saline, the nonselective DA agonists amphetamine or apomorphine, the D1 agonist SKF 38393, or the D2 agonist quinpirole prior to placement in the operant chamber. Treatment with SKF 38393 or quinpirole produced dose-dependent reductions in overall response rates which were similar to those observed with either amphetamine or apomorphine. In addition, treatment with the D2 agonist produced a gradual decline in responding within each test session. These data suggest that preferential stimulation of either D1 or D2 receptors is sufficient in disrupting food-reinforced lever-pressing; furthermore, the extinction-like intrasession decline in responding induced by the D2 agonist suggests that this drug, unlike the others, may have disrupted responding by reducing the reinforcing efficacy of the food. PMID- 2576146 TI - Regional distribution of somatostatin receptor affinity states in rat brain: effects of divalent cations and GTP. AB - In the present work, we have characterized by film radioautography the effects of divalent cations and guanine nucleotide on specific receptor for somatostatin (SRIF) using 125I-TyrO-DTrp8-SRIF14 (125I-ToD8-SRIF) as a ligand. The experiments were performed on coronal 20-microM-thick sections cut at the level of the amygdala, thus allowing to study binding sites in several regions enriched in binding sites (frontal cortex, hippocampus CA1 and dentate gyrus, habenula, basolateral nucleus of the amygdala). In a preliminary set of experiments using brain cortical membranes it was found that 3 mM Mg2+ ions doubled the specific binding of 125I-ToD8-SRIF. However, Mg2+ enhanced equally by a factor of 3 affinities of high- and low-affinity binding sites as evidenced by SMS 201.995 displacement curves without modifying the ratio between high and low affinity sites. In radioautographic studies while SRIF14 and SRIF28 elicited monophasic displacement curves, SMS 201.995 displaced 125I-ToD8-SRIF binding in a biphasic manner in all regions tested but the baso-lateral nucleus of the amygdala. Radioautographic distribution of 125I-ToD8-SRIF binding sites was identical whether the sections were incubated with MgCl2 or with MnCl2 and almost undetectable in the absence of ions. In all structures investigated increasing concentrations of GTP totally inhibited 125I-ToD8-SRIF binding with an IC50 value of 3 microM. In conclusion, our results demonstrate that 125I-ToD8-SRIF-binding sites in brain occur on two different affinity states as assessed by a displacement curve using endogenous ligands and SMS 201.995. According to the comparable effects of divalent cations and GTP, the two subtypes of 125I-ToD8 SRIF-binding sites discriminated by SMS 201.995 are likely to correspond to interconvertible forms of the same receptor coupled to a G protein-transducing system. PMID- 2576147 TI - [Usefulness of determining 2 cell membrane enzymes in bronchial aspirate and lung tissue in patients with cancer of the lung]. AB - The cell membrane enzymes, Alkaline Phosphatase and Gamma Glutamyl Transferase, have been studied in lung aspirates from healthy subjects and lung cancer patients. These enzymes were studied, in the latter, both in healthy and in neoplastic tissue. The enzymatic activity both in the lung aspirate and in the neoplastic tissue was significantly lower in poorly differentiated cancers when compared to well or moderately differentiated tumors. Similarly, analysis revealed that there was a statistically significant decrease in the activity of both enzymes in lung aspirates from patients with bronchogenic tumors when compared to healthy controls. The results obtained in this present work, together with the easiness of obtaining a lung aspirate suggest that these enzymes should be determined in order to obtain further information about the histological origin of lung cancer. These enzymatic changes could be explained with the "fatalism" theory for neoplastic tissue as we explain in this work. PMID- 2576148 TI - The presence of HCO3- does not inhibit alpha-adrenergic increases in proximal tubular intracellular pH. AB - Hormonal stimulation of Na+/H+ exchange increased intracellular pH (pHi) in a dose-dependent manner in proximal tubules suspended in Krebs-Henseleit buffer (KHB) supplemented with 25 mM HCO3- and CO2 (KHB + HCO3). The maximum increase in pHi was approximately 45% of the response observed with segments suspended in bicarbonate-free buffer (KHB-HCO3) and the time required to achieve maximum pHi alterations was significantly increased (p less than 0.05) in the presence of KHB + HCO3 when compared to responses obtained in KHB - HCO3. Dose-response curves for agonist-induced pHi increases were shifted to the right by a factor of 10 for segments suspended in KHB + HCO3. Increases in pHi induced by agonists in KHB + HCO3 were effectively blocked by pretreatment with 10 microM ethylisopropyl amiloride but not with the Cl-/HCO3- inhibitor, DIDS (0.1 mM, 30 min). We conclude that stimulation of alpha-adrenergic receptors on proximal nephrons increased pHi due to activation Na+/H+ exchange and can be detected in the presence of HCO3- although the time course and maximum level of change differ significantly from those observed in a HCO3(-)-free buffer. PMID- 2576149 TI - Modification of membrane protein expression and protein secretion in LLC-PK1 cultures grown on different carbohydrates. AB - Membrane glycoproteins and glycolipids play an important role in epithelial organization, transport and function. To study the effects of exogenous carbohydrates on the expression of glycoproteins, cells of the renal epithelial line LLC-PK1 were cultured on different nutritive carbohydrate sources and on uridine, which is, despite striking differences, known to substitute all essential nutritive functions of glucose. LLC-PK1 cultures were long-term adapted to growth in culture medium containing 0.5, 5, 10 and 25 mM glucose, and 5 mM fructose, galactose and uridine, respectively, as the sole carbohydrate source. These growth conditions elicited adaptive changes in the expression of enzyme activities of alkaline phosphatase and gamma-glutamyltranspeptidase, integral membrane glycoproteins exclusively localized in the apical membrane of LLC-PK1 cells. SDS-PAGE of membrane preparations of adapted LLC-PK1 cells revealed a strong induction of several protein bands between 13.5 and 47 kD in fructose grown cells, while in plasma membranes of cells grown in galactose several protein bands between 62 and 70 kD decreased. Changes in the secretion pattern of proteins into the culture medium were most prominent in uridine-grown cells compared to controls grown on 25 mM glucose. PMID- 2576150 TI - MHC class II glycoprotein expression and resistance to mycobacterial growth. PMID- 2576151 TI - Conjugation system of IncC plasmid RA1, and the interaction of RA1 pili with specific RNA phage C-1. AB - RA1 was the only IncC plasmid that was slightly temperature-sensitive for replication and transfer. At 30 degrees C, RA1 determined constitutive synthesis of conjugative pili and yet was transfer-repressed. Attachment of shaft-adsorbing RNA phage C-1 virions prevented the probable retraction of pili under heat stimulus (55 degrees C). Electron microscopy showed single adsorbed virions at pilus bases where they were thought to have stopped retraction. PMID- 2576152 TI - Pathology of pulmonary vasculitis. PMID- 2576153 TI - [Dysthyroidism in the post-partum period]. AB - Post-partum dysthyroidism are not well understood by obstetricians, but are rather frequent (5.5% of the cases); they usually are the manifestation of a lympho-plasmocytic thyroidism with auto-immune origin. They are encouraged by a genetic predisposition and sometimes by food with a high iodine content. The disease starts with a phase of early thyreotoxicosis, 1 to 3 months following delivery, then later with hypothyroidism (from the 3rd to the 9th month), associated with menstrual disorders, an amenorrhea-galactorrhea syndrome or still, the occurrence of a goiter. Most of the time, the course is favorable, even in the absence of treatment with spontaneous return to euthyroidism within a few months, although the chance of permanent hypothyroidism is however non negligible. The diagnosis is difficult, and the treatment should be the least aggressive possible: beta-blocker during the thyreo-toxicosis phase, supplemental treatment during the hypothyroidism phase. There is a risk of recurrence during subsequent pregnancies. PMID- 2576154 TI - Preparation and developmental toxicity of monoclonal antibodies against rat visceral yolk sac antigens. AB - Thirty clones producing monoclonal antibodies (MCAs) to rat visceral yolk sac (VYS) antigens have been prepared. These MCAs localized by immunofluorescence in the VYS endoderm in vitro and were tested for developmental toxicity by intraperitioneal injection of ascites fluid into pregnant rats on day 9 of gestation. Five of the hybridomas produced MCAs that induced embryonic death, malformation, and growth retardation; the other MCAs had no developmental toxicity. Five MCAs, three teratogenic and two nonteratogenic, were tested for their ability to inhibit pinocytosis in the isolated day 17-VYS. Only the teratogenic MCAs were inhibitory, providing further evidence for the hypothesis that teratogenic antibodies interfere with the nutritional supply to the embryo. PMID- 2576156 TI - The circadian variation of blood pressure and heart rate in patients with hyperthyroidism. AB - The circadian variation of blood pressure (BP) and heart rate (HR) was examined in 18 normal subjects, 15 patients with essential hypertension treated with beta blockers and 21 patients with hyperthyroidism. Most of the patients with hyperthyroidism were also treated with beta-blockers. The 24 hr BP was measured with an ambulatory blood pressure monitoring device (UBP-100) every 5 min. A nocturnal fall in BP and HR was observed in the patients with essential hypertension treated with beta-blockers and the patients with mild to moderate hyperthyroidism as well as normal subjects. On the other hand, in patients with severe hyperthyroidism the nocturnal fall was observed in HR alone, and the fall was small in its amplitude. There was a significant negative correlation between triiodothyronine (T3) level and percentage amplitude of the nocturnal fall in systolic BP (n = 21, r = -0.5, p less than 0.01). However, this relation was not significant in diastolic BP and HR. These results indicate that excess thyroid hormone may modulate the circadian variation of BP and HR. PMID- 2576155 TI - [Treatment of chronic heart failure with positive inotropic agents]. AB - Prognosis of heart failure patients remains poor and stimulates research of new active drugs and therapeutic improvements. Besides diuretic and vasodilating agents, the place of positive inotropic drugs remains to be defined. Long term benefit remains to be demonstrated for Milrinone, Enoximone and Digitalis. However, absence of benefit has been established with Amrinone and beta adrenoceptor agonists. Too many uncontrolled studies have complicated the accurate evaluation of efficacy of these positive inotropic drugs. Purpose of heart failure treatment remains to improve functional status without deterioration of myocardial fibers contractility. The respective roles of cAMP, gAMP and intracellular calcium concerning myocardial fiber longevity remains to be clarified. PMID- 2576157 TI - Evidence for normal thymic export of lymphocytes and an intact RT6a gene in RT6 deficient diabetes prone BB-rats. AB - Diabetes prone BB-rats develop an insulin-dependent diabetes mellitus between postnatal day 60 and 120 in a high incidence. Moreover, even before onset of the diabetes, these animals are deficient in the RT6+ subset of T lineage cells. We here put forward evidence that the export of cells from the thymus is normal in these rats, suggesting a maturational block in the periphery. We show furthermore by Southern blot analysis that diabetes prone BB-rats possess the RT6a gene which is not grossly altered in comparison to that of diabetes resistant strains. PMID- 2576159 TI - Interaction between immune and endocrine systems: effect of luteotrophic hormone (LH) and thymic hormone on surface antigens (Thy1-2, Lyt1 and Lyt2) expression. PMID- 2576158 TI - Thymus-derived and non-thymus-derived T-like cells: the origin and function of cells bearing gamma delta receptors. PMID- 2576160 TI - Immunotechniques for epidemiology of malaria: appropriate tools for integration of primary health care with malaria research and control. AB - Community-based malaria control with integrated primary health care appears to be the most feasible approach for endemic countries in their struggle against malaria. To plan and implement personal protection and vector control measures, there is the need for comprehensive information about local modes of transmission. Experience with insecticide-based vector control programmes and entomological data accumulated over the years has revealed vector systems of extraordinary heterogeneity, creating multifaceted transmission situations. The primary health care-system offers an appropriate structure to collect and evaluate microepidemiological information countrywide. Community and health workers trained and supervised by qualified personnel could be involved in the assessment of clinical, parasitological and entomological indices. Community participation is facilitated if personnel are taught the use of immunotechniques. Tests can be performed on dried material which allows samples to be stored for months without refrigeration, so that transport to and processing in a central laboratory are not subject to time constraints. This paper describes and discusses enzyme-linked immunosorbent assays to determine if antibodies to sporozoites are present in blood collected as dried spots and to identify the origin of bloodmeals using dried mosquito abdomens. PMID- 2576161 TI - The microepidemiology of malaria and its importance to malaria control. AB - Recent studies in West Africa and in Papua New Guinea have shown that the prevalence of malaria can vary widely between neighbouring villages and within different parts of the same village. Both genetic and environmental factors are likely to contribute to these variations. Clustering in households of genetically determined red cell abnormalities, and possibly of immune response genes, may contribute to differences in the prevalence of malaria within a village. Environmental factors probably play the major part in explaining differences between villages. The position of a village in relation to mosquito breeding sites, the design of houses and the level at which anti-mosquito measures are used will all influence the degree to which its inhabitants are exposed to infection. Attitudes to the treatment of a case of malaria may also contribute to local variations in the prevalence of malaria. Malaria parasitaemia and splenomegaly will be less frequent in a community where effective treatment is given immediately at home, or sought promptly from a primary health care worker, than in a neighbouring community where there is a much greater reliance on traditional medicines. Recognition of local variations in the prevalence of malaria is important because identification of the factors responsible for a low prevalence in one village but a high one in a neighbouring community may indicate a possible control measure. Local variations in the epidemiology of malaria must also be taken into account when any kind of malaria intervention trial is planned. PMID- 2576162 TI - Malaria in migrants and travellers. AB - Imported malaria is a growing problem in the world. In part this is a result of greatly increased and more rapid travel and in part a result of a resurgence of malaria in areas partially or completely cleared. Migrants, either refugees or those looking for better opportunities in life, have contributed to the movement of malaria to previously free areas. Failure of travellers to take appropriate action to prevent infection has contributed to the increased incidence of imported malaria. Vectors of malaria may also become travellers and thus contribute to the spread of infection. PMID- 2576163 TI - Current studies related to the development of transmission-blocking malaria vaccines: a review. AB - Transmission-blocking malaria vaccines are expected to induce an immune response which, acting in the mosquito, will prevent its infection. It is generally considered that antigametocyte antibody is one factor in this effect, but there is also evidence that phagocytes and lymphocytes may contribute to blocking mosquito infection. Transmission-blocking immunity develops naturally. Antibody capable of interfering with infection of mosquitoes was shown to persist for 4 months after parasitaemia disappeared. Titres of antibody to a 230 kDa protein in developing Plasmodium falciparum oocysts correlated with the transmission blocking capacity of serum. Monoclonal antibodies have been raised which are capable of blocking infection of mosquitoes by P. falciparum. Some of these interfere with fertilization. The antibodies react with protein expressed in freshly emerged gametes. It should be emphasized that despite progress in laboratory studies of transmission-blocking immunity, there remains a great need for specific epidemiological studies to determine the role of transmission blocking immunity in endemic areas. PMID- 2576165 TI - [Polymyalgia rheumatica, Takayasu's disease and the aortic arch syndrome]. AB - The authors discuss the causes of the aortal arch syndrome in a 65-year-old female patient, whom they observed in conjunction with rheumatic polymyalgia probably associated with Takayasu's disease. During corticoid treatment subjective as well as objective symptoms receded. When the doses were reduced, the original clinical symptoms and laboratory findings reappeared. It is probable that this course escapes attention and is ascribed to other diagnosis. If more attention will be paid to the aortal arch syndrome, it will be possible to diagnose it more often. PMID- 2576164 TI - Possible role for acetylcholine as a neurotransmitter in canine penile erection. AB - In 15 adult dogs, the possible role of acetylcholine as a parasympathetic neurotransmitter in canine penile erection was investigated. Intracavernous injection of increasing dosages of acetylcholine (0.1-100 micrograms) induced a dose-dependent erectile response with increased arterial flow, cavernous smooth muscle relaxation, and venous occlusion. This erectile response was completely abolished after muscarinic blockade by intracavernous injection of 0.1 mg atropine. After cavernous nerve stimulation, atropine injection significantly reduced the pudendal arterial flow (by 25%) and likewise caused a significant reduction in cavernous outflow restriction. Histologic staining showed acetylcholinesterase-positive fibers around the cavernous arteries and within the cavernous erectile tissue. PMID- 2576166 TI - Tardive dyskinesia in outpatients on depot phenothiazine. AB - Two hundred and thirty-two psychiatric Outpatients on depot fluphenazine decanoate for more than six months were examined for Tardive Dyskinesia (TD), using the AIMS rating scale, and the prevalence rates of TD at different criteria of severity were assessed. The prevalence rates ranged from 7% for patients with severe TD to 45% for patients with any degree of TD. The sex distribution of patients with TD showed no bias but the female patients were significantly older than the male patients. Increases in prevalence rates of TD were associated with the combination of an anticholinergic anti-Parkinsonian drug with the depot neuroleptic, and with the concomitant use of an oral neuroleptic with the depot preparation. Implications of these findings for the long-term management of schizophrenia are discussed. PMID- 2576167 TI - [Cordipine in the treatment of patients with exacerbated coronary disease]. AB - The results of pharmacological treatment are presented in a group of 60 patients with exacerbation of coronary disease. The patients were divided into two subgroups: subgroup 1 of 26 patients with intensification of angina of effort, subgroup II of 34 patients with unstable angina. Combined pharmacological treatment was given: nitrates, B-adrenolytic drugs and nifedipine (Cordipin, Krka) Addition of Cordipin produced clinical and electrocardiographic improvement in 44 cases (73%): all patients in subgroup I and 18 (53%) in subgroup II. Cordipin was well tolerated, and produced no serious side effects. PMID- 2576168 TI - [Incidence of accessory adrenal cortex tissue of the inguinal region in the child -results of a prospective study]. AB - Aberrant adrenal cortical tissue is often found in close contact to the urogenital system. In a prospective study covering 150 operations for inguinal hernia, and 110 operations for undescended testes, we looked for aberrant adrenal cortical tissue. In 5.2% of the inguinal hernias and 10.9% of the undescended testes, aberrant adrenal cortical tissue was found. The frequency was higher than reported in the literature. The aberrant adrenal cortical tissue is of clinical importance only in the very rare cases of development of malignant tumours in this tissue. PMID- 2576169 TI - [Imaging diagnosis of central nervous system involvement in panarteritis nodosa]. AB - Central nervous system involvement of periarteritis nodosa is a rare complication of this disease. The diagnosis of CNS manifestation in vasculitis has been improved by using imaging techniques (i.e., magnetic resonance tomography, computed tomography, positron emission tomography). A case of polyarteritis nodosa with CNS involvement is presented; the diagnostic value of magnetic resonance imaging and positron emission tomography is discussed. PMID- 2576170 TI - [The inhibition of succinate, beta-oxybutyrate and glutamate transport in the liver mitochondria of hibernating susliks]. AB - Studies have been made on the permeability of the inner membrane of the liver mitochondria from hibernating and active ground squirrels for succinate, glutamate, hydroxybutyrate and inorganic phosphate. The permeability was calculated from the rate of mitochondrial swelling in 100 mM ammonium salts of the substrates and phosphate. It was shown that the rate of mitochondrial swelling in hibernating animals is 2--3 times lower than in active ones, being essentially identical in a solution of ammonium phosphate. It was concluded that the permeability of the inner mitochondrial membrane for the substrates decreases in hibernating animals, remaining unaffected for phosphate. Calcium-induced activation of membrane phospholipase A2 facilitates the transport of oxidative substrates into the mitochondria of hibernating ground squirrels, significant increase in the mitochondrial respiration being simultaneously observed. The data obtained suggest that inhibition of transport of oxidative substrates is one of the main factors which account for a low respiration rate in the mitochondria of hibernating animals. PMID- 2576172 TI - The effect of sufentanil on intracranial pressure (ICP) in anesthetized dogs. AB - The use of sufentanil in neuroanesthesia has been questioned because of a potential increase in intracranial pressure (ICP) in dogs and humans. The effect of sufentanil administration on ICP was studied in 6 dogs with normal and elevated baseline ICP, anesthetized with nitrous oxide and an intravenous piritramide infusion. No significant change in ICP could be demonstrated over a 30 minute observation period after administration of 2 micrograms/kg of sufentanil. The results indicate that this dose of sufentanil does not increase ICP in moderately hyperventilated dogs under stable anesthetic conditions. PMID- 2576171 TI - [The heterogeneity of the excitatory synaptic inputs in the spinal motor neurons of the frog Rana ridibunda]. AB - The synaptic responses induced in motoneurones by the stimulations of the dorsal root (DR), single afferent fibres and reticular formation (RF) were intracellularly recorded in the isolated frog spinal cord. It was shown that argiopine (the selective blocker of glutamate receptors of non-NMDA type) in concentrations ranging from 3.10(-7) to 1.10(-5) M effectively suppressed the di- and polysynaptic, but not the monosynaptic components of EPSP's induced by DR stimulation. The initial reaction to argiopine consisted of the increase of this monosynaptic component of EPSP. In the same concentrations range, argiopine reduced both mono- and polysynaptic EPSP, evoked by RF stimulation. 2-amino phosphonovaleric acid (1.10(-4) M) did not affect, whereas the kinurenate (1- 2.10(-3) M) completely blocked the amplitude of all kinds of synaptic responses. The various effects of argiopine on the responses induced by microstimulation of presynaptic nerve terminals were observed. The data obtained speak in favour of heterogeneity of monosynaptic excitatory inputs in the motoneurones of frog spinal cord. Being the glutamatergic by nature, the inputs differ in the properties of postsynaptic receptors. All of these receptors concerning to non NMDA-type can be divided to argiopine-sensitive and argiopine-resistant. The first seem to be involved in the monosynaptic connections of RF and the second- in those of primary afferents with motoneurones. PMID- 2576173 TI - Effects of adrenaline, an alpha 2-adrenoceptor agonist, the volume of injection, and the global pain state of the animal on the activity of epidural sufentanil. AB - A study was made of the effects of different volumes of injection product, adrenaline, the alpha 2-adrenoceptor-agonist medetomidine and Mycobacterium butyricum on epidural sufentanil in the rat. Increasing the volume of epidural sufentanil, and similarly decreasing the concentration of the injection product, resulted in a potentiation of the analgesic properties of epidural sufentanil without affecting the effects of the drug on the pinna and cornea reflexes and on muscle tonus. An analogue effect was observed if rats were tested for epidural analgesia during a chronic pain phase after inoculation with Mycobacterium butyricum. Adding adrenaline to epidural sufentanil also resulted in an increased analgesia but there was also a minor potentiation of all other behavioural parameters measured. The alpha 2-adrenoceptor-agonist medetomidine, clearly potentiated all behavioural effects induced by epidural sufentanil. As a consequence, there was no gain in specificity for epidural analgesia. Medetomidine, however, clearly reversed the normally observed skeletal muscle rigidity into a muscle hypotonia. Globally, these results thus indicate that manipulations of the volume of injection, the additional treatment with other drugs and the pain state of the animal can alter the activity of epidural sufentanil. Therefore, it might be concluded that the differences in the duration of analgesia observed with epidural sufentanil between human and animal studies can be partially explained in terms of differences between the experimental conditions. PMID- 2576174 TI - Cerebrospinal fluid neurotransmitters of the newborn with neonatal asphyxia. AB - (1) This is the first study to demonstrate that CSF 5HTP, HVA and DOPAC of asphyxiated newborns are higher than those of healthy newborn infants. (2) This study shows Neurochem, a newly developed neurochemical analyzer, is useful equipment in neonatal neurological research. PMID- 2576175 TI - [Blocking actions of l-stephanine, xylopine and 7 other tetrahydroisoquinoline alkaloids on alpha adrenoceptors]. AB - The blocking action and selectivity of 9 tetrahydroisoquinoline alkaloids on alpha adrenoceptors have been investigated in isolated tissues. Dehydrostephanine and berbamine suppressed the inhibition of clonidine for the electrically stimulated twitch response of rat vas deferens, with pA2 values of 5.36 and 5.49, respectively. l-Crebanine, l-tetrahydrocoptisine, berberine, l-stepholidine and l tetrahydropalmatine had obvious blocking effects on alpha 1 and alpha 2 adrenoceptors. l-Stephanine and xylopine could competitively inhibit anococcygeus muscle contraction induced by phenylephrine with pA2 values of 6.76 and 6.68, respectively. These 2 alkaloids showed no effect on the inhibition of clonidine for contractile response of rat vas deferens to field stimulation, and their selectivity ratios to block alpha 1 and alpha 2 adrenoceptors were 57.5 and 47.9, respectively. These results indicate that l-stephanine and xylopine are 2 potent and highly selective alpha 1 adrenoceptor blockers. PMID- 2576176 TI - Accident simulation as a new therapy technique for post-traumatic stress disorder. A case study. AB - Data are presented from clinical interviews and psychological tests of a helicopter pilot who had survived a helicopter crash. Within a week, the pilot developed severe stress reactions after the crash, dominated by guilt feelings, nightmares and fear of not being able to fly. Helicopter-accident training simulating a helicopter crashing into the water was used as part of the treatment. The therapeutic value and limitations of this type of treatment are discussed. The main benefit seemed to be the extinction of traumatic helplessness and the reestablishment of a positive response-outcome expectancy. Existential conflicts were not covered by the simulator training. PMID- 2576177 TI - Treatment of some cases in child psychiatry with incisive neuroleptic drugs. AB - The authors report on the administration of incisive neuroleptic drugs in child psychiatry. The drugs were applied in schizophreny, obsessive syndromes and especially in tics. They administered pimozide, haloperidol, penfluridol and isofloxythepin. The results were often better than in the case of sedatives. The authors believe that incisive neuroleptic drugs deserve greater application in these indications as well as in child psychiatry. PMID- 2576178 TI - Clinical and molecular impact of inhibition of IMP dehydrogenase activity by tiazofurin. AB - The impact of tiazofurin on inhibition of IMP dehydrogenase was discussed at the clinical and molecular levels. 1. Evidence was provided for the role of IMP dehydrogenase and guanylates in the expression of the neoplastic program in cancer cells with particular relevance to human leukemic cells. 2. The argument for expecting an impact of tiazofurin in human myelocytic cells was provided. 3. Similarity of the kinetics of human leukemic cell IMP dehydrogenase to the rat hepatoma enzyme was documented. 4. New evidence was provided for the role of salvage in chemotherapy and the function of hypoxanthine in inhibiting guanine salvage. 5. The action of tiazofurin and retinoic acid was reported in HL-60 leukemic cells. 6. The effect of tiazofurin and retinoic acid on proliferation and cytotoxicity was outlined for hepatoma 3924A cells. 7. The effect of guanine on induced differentiation by tiazofurin and retinoic acid was examined. 8. Biochemical basis was provided for the lack of development of resistance in patients treated with tiazofurin. 9. Presumptive evidence was provided that tiazofurin treatment induced differentiation of leukemic cells in the patients. 10. The molecular biology of tiazofurin-induced differentiation in K-562 cells was reviewed with the possible relevance to clinical treatment that tiazofurin might also act through down-regulation of ras oncogene. PMID- 2576179 TI - Regulation of the activity of tyrosine hydroxylase in the central nervous system. AB - Among a variety of factors known to affect the activity of tyrosine hydroxylase, catecholamines, cyclic AMP-dependent protein kinase, calmodulin-dependent protein kinase II, and polyanions resulted in the reversible modulation of the enzyme activity to a greater extent than the other factors. The in vitro experiments suggested that the inactivation of the enzyme by catecholamines, the end products of the enzyme, and the activation by cyclic AMP-dependent protein kinase might be most important in controlling the activity of the enzyme. Incubation of the enzyme with catecholamines at a concentration as low as 10-100 nM resulted in a rapid inactivation, and the inactivated enzyme was found to be more stable than the original uninactivated enzyme. The inactive/stable form of the enzyme exhibited no activity under the physiological conditions. Several lines of evidence indicated that tyrosine hydroxylase might usually exist as the catecholamine-induced inactive/stable form in the nervous system. This inactive form of the enzyme was markedly activated by cyclic AMP-dependent protein kinase. This conversion of the enzyme induced by cyclic AMP-dependent protein kinase was a dramatic one from the almost completely inactive form to the extremely active form having an activity as high as 2,800 units per mg of protein, which was the highest so far reported when the enzyme activity was measured at the physiological pH (pH 7). The co-operative action of cyclic AMP-dependent protein kinase, calmodulin-dependent protein kinase II, and polyanion were also examined. Most of the studies on the regulatory mechanism for tyrosine hydroxylase so far reported have been done with the enzyme from the rat. Tyrosine hydroxylase from human pheochromocytoma was found to be remarkably activated by cyclic AMP dependent protein kinase. Calmodulin-dependent protein kinase II and polyanion also modulated the activity of the human enzyme. These results suggest that tyrosine hydroxylase may be regulated in a similar manner in the human and the rat. PMID- 2576180 TI - Characterization of genomic DNA, mRNA and enzyme protein in cases of HPRT deficiency. AB - 1. Immunological quantitation of the HPRT proteins, together with DNA and RNA studies have defined further the heterogeneous nature of HPRT-deficiency in our patients. 2. These studies have dictated possible approaches for further characterisation of the HPRT enzyme in our patients. In the two Lesch-Nyhan patients, both the protein and the usual cDNA approach would appear difficult. 3. A BamHI polymorphism has been detected in Patient A. 4. Sequence data confirmed the creation of this BamHI site by a single C----T transition at position 602 in the coding sequence. 5. Sequencing of other patients is proceeding and use is being made of the Polymerase Chain Reaction (PCR)10 for amplification of specific segments of HPRT coding sequence. PMID- 2576181 TI - Activity of 2-chloro-2'-deoxyadenosine in chronic lymphocytic leukemia, hairy cell leukemia, and autoimmune hemolytic anemia. PMID- 2576182 TI - Purine and pyrimidine metabolism of normal and leukemic lymphocytes. PMID- 2576183 TI - Restriction fragment length polymorphisms of HPRT and APRT genes in Japanese population. PMID- 2576185 TI - Molecular-genetic study of Duchenne and Becker muscular dystrophies: deletion analyses of 45 Japanese patients and segregation analyses in their families with RFLPs based on the data from normal Japanese females. AB - This study consisted of 1) molecular deletion analyses in patients with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) using the entire cDNA for the DMD gene as hybridization probes, 2) RFLP analyses in a large number of Japanese normal women using 11 DMD-linked cloned DNAs as probes, and 3) segregation analyses with these RFLP data in 17 DMD families in which prenatal or carrier diagnosis was required. The deletion study showed that 18 (43%) of 42 male DMD patients had a deletion within the DMD gene, while no detectable deletion was found in 3 BMD patients. These deletions were preferentially observed at the 5' end of the DMD gene, while no deletion was found in the 3' portion of the gene. Of a total of 15 RFLPs detected with the 11 probes, one was a new RFLP (probe/enzyme: P20/MspI). In 6 RFLPs, the allele frequencies in the Japanese were statistically different from those in the Caucasian. Based on the RFLP data combined with the result of the deletion study, an estimated diagnostic rate for prenatal diagnosis and/or carrier detection in the Japanese DMD families was 63%. The real diagnostic rate obtained from the prenatal and carrier diagnoses, which were practically performed in 17 families, corresponded to the estimation. A protocol useful for the diagnosis in Japanese DMD families is presented. PMID- 2576184 TI - [Novel immunotherapeutic models for neoplastic diseases of the urogenital tract with special attention to bladder carcinoma]. AB - In this review article some novel immunotherapeutic models as well as some new concepts concerning the unspecific and specific T-cell stimulation are discussed briefly. Some of these immunotherapeutic models are restricted to bladder cancer; the others have a generalized meaning. One model, restricted to bladder cancer, is based on the enzymatic++ pretreatment of effector-cells (macrophages, NK cells), followed by their instillation in the patient's bladder. The other bladder tumor restricted model includes the direct in situ activation of effector cells by proteases and lipases. A third model for the treatment of bladder tumor implies a presensitization of patient's TD/TDTH-cells, followed by the treatment of patient's bladder tumor cells by some, common haptenic group. In addition, some novel ways of immune stimulation, partly by circumventing the (tumor specific) immune tolerance, based on the cross-linking of crucial membrane structures on T4- and T8-cells or on a managed, controlled APC: T-cell interaction, are discussed. The details inclusively the comprehensive special literature can not be brought in this review article; they should be dealt with in special papers being in preparation. PMID- 2576186 TI - Impact of media on drug consumption. AB - A patient with chronic tranquilizers abuse which decided according to the media to consume "natural and soft products" is described. The implication of such a decision is discussed and a pharmacological approach in such situation is suggested. PMID- 2576187 TI - [Antibodies directed against the cytoplasm of granulocytes. Diagnostic value in vasculitis]. AB - The demonstration of antibodies directed against granulocyte cytoplasm in Wegener's disease and in the microscopic forms of polyarteritis nodosa led to the proposal that these antibodies could be used as a diagnostic tool and a means to monitor the evolution of these diseases. However, the presence of these antibodies in different pathological situations and, in particular, in syndromes not related to vasculitides, poses the question as to their specificity. In addition, the observation of dissociated reactions between the methods available for the detection of these antibodies (indirect immunofluorescence, radioimmunological assay), like the existence of different morphological aspects seen in immunofluorescence, favor the hypothesis of different antigenic determinants, whose recognition could contribute to the nosology and pathophysiology of these diseases. We performed a retrospective study based on 42 positive results (paired execution of both detection techniques), in order to characterize the corresponding anatomic and clinical states. We confirmed the classical positivity in Wegener's disease and microscopic forms of polyarteritis nodosa, justified the paired running of both detection assays because of dissociated results and false positives found by immunofluorescence, corroborated the presence of antibodies in conditions apparently unrelated to vasculitides, and specified the different aspects observable by immunofluorescence, thus demonstrating the reality of different antigenic determinants. PMID- 2576188 TI - Restriction fragment length polymorphism of human mitochondrial DNA in a sample population from Apulia (southern Italy). AB - Restriction fragment length polymorphism (RFLP) of human mitochondrial DNA was analysed in a sample of 87 subjects from Apulia (South Italy) by the restriction enzymes HpaI, BamHI, HaeII, MspI, AvaII, and HincII using total blood cell DNA probed by human mtDNA from placenta. Five BamHI morphs were observed, two of which are new (BamHI-4 and -5), as well as one new AvaII morph (AvaII-28). The association BamHI-4/AvaII-28 enables us to demonstrate for the first time two polymorphic BamHI sites present together in the same mtDNA molecule. In agreement with historical data the Apulian sample has been shown to be the most heterogeneous Italian population so far tested. PMID- 2576189 TI - Mitochondrial DNA polymorphism detected with the restriction enzymes BstNI and BclI in a French Canadian population. AB - The enzymes BstNI and BclI were used to detect various human mitochondrial DNA RFLPs in a sample of 104 unrelated French Canadians. These sequence variations were found in total white blood cell DNA probed with whole human mitochondrial DNA. With BstNI, 6 mitochondrial DNA restriction patterns (morphs) were identified. BstNI morphs 2-6 each differ from morph 1 by one single distinct restriction site gain or loss on the mitochondrial DNA molecule. Although BstNI morph 1 was found in most of the subjects (80%), each other morph was observed at a frequency of at least 3%. With the enzyme BclI, 4 different morphs were detected. Morphs 2-4 also result from different single restriction site alteration as compared with BclI morph 1. The morph 1 was clearly the most frequent (95%) while morphs 3 and 4 were present in only 1% of the subjects. These data indicate that the enzyme BstNI and, to a much lesser extent, the enzyme BclI detect mitochondrial DNA polymorphism in Caucasians. They are therefore of interest for population genetics studies. PMID- 2576190 TI - Subtypes of HLA-DQ and -DR defined by DQB1 and DRB1 RFLPs: allele frequencies in the general population and in insulin-dependent diabetes (IDDM) and multiple sclerosis patients. AB - We have used the HLA-DQB1 gene as a Southern hybridization probe with TaqI digested genomic DNA in a study of 600 haplotypes from unrelated individuals and have characterized HLA-DQB1 RFLP patterns associated with the DR specificities DR1-DRw10 and DN1. For six of the specificities (DR2, 4, w6, 7, w8 and 9), we have also identified subtypes (multiple DQB1 band patterns). In a previous study (Cox et al. 1988), we identified RFLPs and subtypes with a DRB1 probe. Using the present results from DQB1 RFLPs to supplement those from DRB1 RFLPs, it was possible to discriminate among all the DR specificities with the exception of a minority of DR7 and DR9 subtypes. A comparison of DQB1 and DRB1 subtypes in the same subjects showed strong linkage disequilibrium for subtypes of some but not all DR specificities. We have also determined the allele frequencies of the DQB1 subtypes in controls and in patients with insulin-dependent diabetes mellitus (IDDM) or multiple sclerosis (MS). A consideration of subtypes in patients and controls indicated that for most DR specificities, neither IDDM nor MS was more strongly associated with any of the DQB1 subtypes than with the serologically defined DR antigens. The exceptions were the DQB1 patterns corresponding to the DQw3.2 subtype of DR4 and the rarer subtype of DR2, which were found in higher frequency in IDDM patients, as has been previously reported. PMID- 2576191 TI - [Endocorporeal lithotripsy using a pulsed laser]. AB - Intracorporeal lithotripsy of urinary calculi by pulsed dye laser has recently enriched the urologist's therapeutic arsenal. We recall the in vitro studies and animal experimentations which demonstrated the feasibility of laser lithotripsy and the absence of harmful tissue damage. The ideal indications for intracorporeal lithotripsy are ureteral stones accessible by rigid and, more especially, flexible ureteroscopy. The results of the first published series using this technique are very encouraging. PMID- 2576192 TI - Evaluation of the antifibrillatory activity of fluorinated derivatives of indenolol and nadolol in isolated rabbit and rat hearts: comparison with propranolol. AB - The effects of indenolol and nadolol and of their respective fluorinated derivatives on ventricular fibrillation threshold were compared with propranolol in Langendorff-perfused rabbit hearts. Their effects on aconitine-induced ventricular tachycardia and fibrillation were also evaluated in Langendorff perfused rat hearts. Propranolol, indenolol and indenolol fluorinated derivative produced significant dose-dependent increases in ventricular fibrillation threshold at all tested concentration levels. These compounds have also caused significant increases in the amount of aconitine required to produce ventricular tachycardia and fibrillation. Nadolol and nadolol fluorinated derivative did not produce any significant changes in the above-mentioned parameters except a small, but statistically significant, increase in ventricular fibrillation threshold produced by the highest concentration (2.64 microM) tested of nadolol fluorinated derivative. On a dosage basis, the order of potency of these compounds is indenolol fluorinated derivative greater than propranolol greater than indenolol greater than nadolol fluorinated derivative greater than nadolol. These results suggest that additional properties of beta-adrenergic blockers, such as membrane stabilizing effects, may contribute to their antifibrillatory activity and that fluorination may tend to increase it. PMID- 2576193 TI - Beta-blockade in the ischemic reperfused working rabbit heart: dissociation of beta-adrenergic blocking and protective effects. AB - The cardioprotective effects of the beta-blocking drugs (dl-nebivolol, d nebivolol, propranolol, atenolol, dilevalol and pindolol) were tested in the isolated working rabbit heart. The effects of l-nebivolol, having little beta adrenoceptor blocking activity, were also studied. The hearts were subjected to 25 min ischemia, followed by 30 min of reperfusion. In solvent-treated hearts, ischemia resulted in a considerable loss of function. The mean functional recovery of one of the most sensitive parameters, i.e. aortic flow, was only 6%. Pretreatment either with dl-nebivolol, d-nebivolol, l-nebivolol or propranol significantly improved cardiodynamic function. Recovery after pretreatment with atenolol, dilevalol and pindolol (less than 10 mg/l) was not significantly improved when compared to solvent-treated hearts. The results suggest that the protective effects of some beta-blockers are most probably not related to beta adrenoceptor blocking activity. PMID- 2576194 TI - Blood pressure lowering action and alpha-adrenolytic effect of adimolol in rats. AB - Adimolol is a new antihypertensive agent with strong nonselective beta- and moderate alpha-adrenolytic properties. In order to elucidate whether the alpha adrenoceptor blockade by adimolol may contribute to the blood pressure lowering action of the compound, we tested 1) the effect on heart rate and blood pressure in conscious spontaneously hypertensive rats after oral administration and 2) the influence on the pressor effect of intra-arterially injected noradrenaline in autoperfused rat hindquarters after i.v. administration. Adimolol was compared with propranolol, labetalol, prazosin and combinations of propranolol plus low dose prazosin. In conscious spontaneously hypertensive rats, labetalol, propranolol plus low-dose prazosin and adimolol lowered blood pressure considerably in parallel with heart rate. Propranolol alone acutely lowered heart rate, but not blood pressure. Low-dose prazosin alone lowered blood pressure and heart rate only moderately. In autoperfused hindquarters, the pressor-response curve to noradrenaline was dose-dependently shifted to the left by propranolol and to the right by labetalol or prazosin. The leftward shift by propranolol could be antagonized dose-dependently by addition of low doses of prazosin. Adimolol, at doses of 0.1, 10 and 20 mg/kg, did not significantly influence the pressor-response curve to noradrenaline in this model, whereas a slight but significant shift to the left was observed with 1 mg/kg. In summary, the cardiovascular effects of adimolol in rats cannot completely be explained by beta adrenoceptor blockade. They can be mimicked by the concomitant administration of a beta-adrenoceptor blocking and an alpha-adrenoceptor blocking agent. We conclude that the alpha-adrenolytic activity of adimolol can be demonstrated in vivo and may contribute to the blood pressure lowering action of the compound in rats. PMID- 2576196 TI - Verapamil interacts in vitro with alpha 2-adrenoceptors but does not modify alpha 2-receptivity in vivo. AB - The kind of interaction of two structurally different calcium channel blockers (verapamil and nicardipine) with both alpha 2-adrenergic agonist and antagonist binding on human platelets was investigated. Only verapamil, but not nicardipine, interacted in vitro with platelet alpha 2-adrenoceptors on [3H]-yohimbine or [3H] UK 14,304 binding. Verapamil behaves as a weak antagonist competitor for alpha 2 adrenoceptors. In patients with mild essential arterial hypertension, the number of platelet alpha 2-adrenoceptors as well as velocity of aggregatory response to adrenaline, are significantly decreased: -21 and -25%, respectively (p less than 0.05). Verapamil (120 mg t.i.d. orally during 1 month) failed to modify the platelet alpha 2-adrenoceptor number or the adrenaline-induced platelet aggregation in hypertensive patients. These results show that, although interacting in vitro, verapamil does not modify the alpha 2-adrenergic receptivity after 1 month treatment in humans. PMID- 2576195 TI - Alpha 2-adrenoceptor-mediated inhibition of gastric acid secretion by medetomidine is efficiently antagonized by atipamezole in rats. AB - The effect of a novel highly selective alpha 2-adrenoceptor agonist, medetomidine (4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole), was studied on gastric secretion in conscious and anaesthetized rats. Medetomidine (3-30 micrograms/kg s.c.) inhibited basal gastric acid and fluid output in conscious rats in a dose dependent manner, while in anaesthetized rats no effect was observed when administered i.v. at the doses of 1-1000 micrograms/kg. Furthermore, medetomidine did not modify gastric acid output stimulated by infusion of histamine i.v. in anaesthetized rats, suggesting also that a medetomidine-induced change in gastric secretion does not involve any action on histamine H2-receptors. Furthermore, evidence was given indicating that alpha 2-adrenoceptors mediate the antisecretory action of medetomidine, since a low dose (0.1 mg/kg s.c., -30 min) of a selective alpha 2-adrenoceptor antagonist, atipamezole [MPV 1248, 4-(2-ethyl 2,3-dihydro-1H-inden-2-yl)-1H-imidazole] efficiently antagonized the effects of medetomidine (30 micrograms/kg s.c.) in conscious rats. In summary, medetomidine inhibits gastric secretion in the rat via alpha 2-adrenoceptor activation, the antisecretory action being blocked by atipamezole. Probably due to its high specificity for alpha 2-adrenoceptors, medetomidine did not show a stimulatory effect on gastric acid secretion in anaesthetized rats. PMID- 2576198 TI - [Transdermal treatment using the betablocker mepindolol]. PMID- 2576197 TI - Synthesis and biological properties of novel triazolopyrimido-pyrimidine-5,8 diones. AB - The synthesis of novel 1,2,4 triazolo[2,3,4-c,d]pyrimido[4,5-d]pyrimidine derivatives has been described from N-substituted amides of 1,2,3,4-tetrahydro-6 methyl-2-oxo-4-thio-5-pyrimidinecarboxylic acid 1. Amides 1 treated with 80% hydrazine hydrate, followed by aqueous-ethanolic formaldehyde form substituted triazolo[4,3-c]pyrimidines which cyclize in pyridine to triazolopyrimidopyrimidine derivatives 4. Attention has been paid to the synthesis of the 4-arylidenehydrazinopyrimidines 3. Some compounds have been tested for antibacterial and anticancer activities and for action on CNS. PMID- 2576199 TI - [Human pharmacologic studies on transdermal administration of mepindolol. Pharmacodynamic and orienting pharmacokinetics]. AB - The pharmacodynamic effects of acute and repeated application of a transdermal patch (BIO TSD) containing 20 mg of the beta-receptor blocking agent mepindolol were assessed in 13 normotensive male volunteers. Orienting measurements of mepindolol serum levels were performed additionally. At rest, the effects on blood pressure and heart rate were very limited. However, during submaximum ergometer exercise, significant systemic beta-blocking effects were observed, especially after 5 days treatment. Repeated administration did not induce tachyphylaxis but resulted in an enhanced efficacy. The mepindolol serum concentrations were markedly lower than those measured after oral application of the drug. No systemic or local adverse reactions nor any relevant changes in laboratory parameters were observed. PMID- 2576200 TI - Transdermal delivery of mepindolol and propranolol in normal man. 1st communication: study design, clinical and pharmacodynamic aspects. AB - In the present study the beta-adrenoreceptor blocking effects of acute and repeated transdermally delivered mepindolol (20 mg/9.8 cm2 patch) and propranolol (40 mg/9.8 cm2 patch) on supine and stimulated circulatory function (isoprenaline infusion, isometric hand grip, delayed auditory feed-back) in nine healthy male volunteers were assessed. The study was conducted in a placebo-controlled double blind cross-over fashion, with three one-week treatment courses randomly allocated in a period-balanced fashion. Treatment phases were separated by a one week wash-out phase. The placebo and mepindolol patch were well tolerated, whereas the propranolol patch caused skin irritation and itching in most subjects, and even vesicular lesions in 3/9 subjects. Acute and repeated 24 h application of the propranolol patch caused only small and clinically not relevant changes of heart rate and blood pressure. Acute application of the mepindolol patch induced only mild blunting of the diastolic blood pressure and heart rate responses to isoprenaline i.v. infusion at 8 h. However, the isoprenaline responses were nearly abolished after one week repeated 24 h application of the mepindolol patch, in a stable and protracted fashion. The circulatory responses to isometric handgrip and delayed auditory feedback tended to be reduced, but to a smaller extent than for the isoprenaline test. Repeated application of mepindolol via the investigational device for transdermal drug delivery (BIO TSD) thus resulted in stable and protracted beta-adrenoreceptor blockade. PMID- 2576201 TI - Transdermal delivery of mepindolol and propranolol in normal man. 2nd communication: pharmacokinetic and neuro-endocrine aspects. AB - The plasma and urinary pharmacokinetics of mepindolol and propranolol were assessed in nine healthy volunteers after single and 1-week daily repeated application of the drugs by a novel transdermal delivery system (BIO TSD). Qualitatively, the time courses of the plasma concentrations for both compounds were similar and indicative of effective drug input. On the first day of the treatment courses plasma levels rose slowly, reaching their observed maximum after 24 h. The latter still was in the rising phase of the curve and further input on longer application is likely. After 1 week daily repeated application apparent steady state conditions were reached. The plasma concentrations were low in comparison to the levels reported for oral dosing. Only small amounts of unchanged drug were excreted via urine. The effects of the investigational treatments on supine-resting and stimulated neuroendocrine variables were assessed also. A blunting of the adrenaline response to delayed auditory feed back mental stress testing (DAF) was consistently observed after propranolol, but not after mepindolol. Noradrenaline responses to DAF were not altered. No consistent effects were observed in terms of the adrenaline responses to 3 min isometric handgrip testing (IHG). Noradrenaline responses to IHG were slightly blunted, relative to placebo on the first day when propranolol and mepindolol were applied. This was probably related to the usually high responses to placebo as reference. At the end of 1 week repeated application of the patches mean supine resting plasma renin activity (PRA) was significantly reduced by propranolol but not by mepindolol, and the mean PRA responses to 5 min i.v. infusion of isoprenaline was reduced by both. PMID- 2576202 TI - Evaluation of the therapeutic effect of transdermal beta-blocker therapy in patients with essential hypertension. AB - Transdermal drug delivery has been applied to various agents in an effort to decrease the frequency of drug administration and improvement of the patients compliance. In the present study, it could be demonstrated that transdermal monotherapy (BIO TSD) with a beta-blocker (20 mg mepindolol) in patients with essential hypertension led to an effective 24 h blood pressure lowering effect within 1 week (160.1 +/- 6.1 mmHg/95.8 +/- 8.3 mmHg vs. 136.8 +/- 7.2 mmHg/84.3 +/- 5.0 mmHg; p less than 0.05). Also a reduction of excessive blood pressure peaks in the circadian blood pressure profiles was observed. Studies comparing transdermal with oral beta-blocker administration in hypertensive patients would further substantiate the value of this new therapeutic system as an antihypertensive treatment. PMID- 2576203 TI - [Anti-ischemic action of the transdermally applied beta-receptor blocker, mepindolol in patients with stable angina pectoris]. AB - A new transdermal system (BIO TSD) containing the beta-adrenergic blocker mepindolol was assessed in a placebo controlled clinical trial in 12 patients with coronary heart disease. On therapy, the number of anginal attacks and the consumption of oral nitroglycerin (glyceryl trinitrate) were reduced significantly. During ergometer exercise the exercise tolerance was improved and the ischemic ST-segment depression was reduced significantly. Holter monitoring revealed significant reductions of the number of manifest and silent episodes and the total duration of ischemia. No relevant side effects were observed. PMID- 2576204 TI - Influence of various adrenergic compounds on plasma potassium levels in conscious dogs and anaesthetized domestic pigs. AB - The influence of various compounds with affinity to beta-adrenoceptors on plasma potassium levels was investigated in conscious dogs and anaesthetized pigs. There was a marked fall, amounting to about 1 mmol/l following salbutamol and pirbuterol but nearly no effect following dobutamine and xamoterol. In dogs the hypokalaemic effect of salbutamol was augmented when prazosin was additionally applied. It is concluded, that the plasma potassium level is reduced mainly by beta 2-adrenoceptor stimulation. Blocking of alpha-adrenoceptors enhanced this effect and should therefore be avoided when beta 2-agonists are used therapeutically. PMID- 2576205 TI - Exercise testing of the chronic effects of bunazosin hydrochloride on dilated cardiomyopathy. AB - Bunazosin hydrochloride (Detantol) was administrated in 3-mg oral doses to 10 patients (6 males and 4 females, average 49.9 years) with dilated cardiomyopathy (DCM) of class II in the NYHA functional classification. The patients were observed for changes in their hemodynamics at rest, chest X-ray, echocardiography, humoral factors and symptom-limited exercise tolerance with treadmill testing before treatment and 4 and 8 weeks after administration. All but the left ventricular end-diastolic diameter after 8 weeks were unchanged. Of the humoral factors, only aldosterone decreased significantly during the treatment. On the other hand, the duration of symptom-limited exercise was prolonged significantly, and for a given exercise load, a reduction of heart rate and systolic blood pressure as well as a drop in the pressure-rate product occurred at 8 weeks after administration. Therefore, bunazosin appears to improve cardiac function and exercise tolerance in the patients with DCM, at dosages which do not affect hemodynamics at rest. PMID- 2576206 TI - A double-blind comparative trial of astemizole and terfenadine for the treatment of hay fever. AB - Astemizole, a new long acting and non sedative antihistamine, and Terfenadine, an H1 antagonist widely used, were compared in a randomized double-blind study over 4 weeks in 55 patients suffering from hay fever. The clinical symptoms were recorded daily from each patient on a 4-point scale from 0 = none to 3 = severe. After 2 weeks of therapy and at the end, the total clinical score was evaluated and both the investigator and the patient made an overall assessment of the therapeutic effect. Both drugs were effective in reducing nasal and ocular symptoms, but the clinical response tended to be better with Astemizole than Terfenadine. The difference between the two drugs, however, was statistically significant (p less than 0.05) only after 2 weeks of treatment. Some side effects, including drowsiness, were observed with similar incidence in both treatment groups. Astemizole appears to be a simple, effective and safe therapy for hay fever. PMID- 2576208 TI - [Dental traumatology and present day pedodontic care]. PMID- 2576207 TI - Conformational changes induced by the transforming amino acid substitution in the transmembrane domain of the neu oncogene-encoded p185 protein. AB - The neu oncogene is frequently found in certain types of human carcinomas and has been shown to be activated in animal models by nitrosourea-induced mutation. The activating mutation in the neu oncogene results in the substitution of a glutamic acid for a valine at position 664 in the transmembrane domain of the encoded protein product of 185 kda (designated p185), which, on the basis of homology studies, is presumed to be a receptor for an as yet unidentified growth factor. It has been proposed that activating amino acid substitutions in this region of p185 lead to a conformational change in the protein which causes signal transduction via an increase in tyrosine kinase activity in the absence of any external signal. Using conformational energy analysis, we have determined the preferred three-dimensional structures for the transmembrane decapeptide (residues 658-667) of the p185 protein with valine and glutamic acid at the critical position 664. The results indicate that the global minimum energy conformation of the decapeptide from the normal protein with Val at position 664 is an alpha-helix with a sharp bend (CD conformation at residues 664 and 665) in this region, whereas the global minimum conformation for the decapeptide from the mutant transforming protein with Glu at position 664 assumes an all alpha-helical configuration. Furthermore, the second highest energy conformation for the decapeptide from the normal protein is identical to the global minimum energy conformation for the decapeptide from the transforming protein, providing a possible explanation why overexpression of the normal protein also has a transforming effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576209 TI - NGF receptor reexpression and NGF-mediated cholinergic neuronal hypertrophy in the damaged adult neostriatum. AB - Adult cholinergic interneurons of the neostriatum are not immunoreactive for monoclonal antibody to NGF receptor, whereas the developing neostriatum is immunoreactive for this same antibody. Chronic NGF infusion into the adult neostriatum resulted in reexpression of the NGF receptor such that many cholinergic interneurons became immunoreactive for NGF receptor. NGF infusion dramatically increased the size and choline acetyltransferase immunoreactivity of these same cholinergic neurons. Additionally, in situ hybridization demonstrated an increase in the number of cells expressing NGF receptor mRNA in the NGF infused striatum. These findings indicate that central cholinergic neurons which lose their NGF receptors during postnatal development will resume their NGF responsiveness when the tissue is damaged. Such a damage-induced mechanism may act to enhance the action of trophic factors, including NGF, released at the site of injury and enhance the responsiveness of damaged CNS neurons to exogenously administered trophic factors. PMID- 2576211 TI - Recombination events suggest potential sites for the Huntington's disease gene. AB - The Huntington's disease gene (HD) maps distal to the D4S10 marker in the terminal 4p16.3 subband of chromosome 4. Directed cloning has provided several DNA segments that have been grouped into three clusters on a physical map of approximately 5 X 10(6) bp in 4p16.3. We have typed RFLPs in both reference and HD pedigrees to produce a fine-structure genetic map that establishes the relative order of the clusters and further narrows the target area containing the HD gene. Despite the large number of meiotic events examined, the HD gene cannot be positioned relative to the most distal cluster. One recombination event with HD suggests that the terminal-most markers flank the disease gene; two others favor a telomeric location for the defect. Efforts to isolate the HD gene must be divided between these two distinct intervals until additional genetic data resolve the apparent contradiction in localization. PMID- 2576210 TI - Proliferation and differentiation of embryonic chick sympathetic neurons: effects of ciliary neurotrophic factor. AB - At early developmental stages (embryonic day 7, E7), chick paravertebral sympathetic ganglia contain a cell population that divides in culture while expressing various neuronal properties. In an attempt to identify factors that control neuronal proliferation, we found that ciliary neurotrophic factor (CNTF) specifically inhibits the proliferation of those cells expressing neuronal markers. In addition, CNTF affects the differentiation of sympathetic ganglion cells by inducing the expression of vasoactive intestinal peptide immunoreactivity (VIP-IR). After 1 day in culture, tyrosine hydroxylase immunoreactivity (TH-IR) was expressed by about 86% of the cells whereas VIP-IR was virtually absent. In the presence of CNTF, 50%-60% of the cells expressed VIP IR after 4 days in culture; however, none of the cells expressed VIP-IR in the absence of CNTF. These results, and the demonstration of cells that express both VIP and TH-IR, indicate that VIP is induced in cells that initially express tyrosine hydroxylase. The findings suggest a potential role for CNTF as a factor affecting the proliferation and differentiation of developing sympathetic neurons. PMID- 2576212 TI - Intercellular signaling as visualized by endogenous calcium-dependent bioluminescence. AB - Bioluminescence in the hydrozoan coelenterate Obelia results from calcium activation of a photoprotein contained in light-emitting cells (photocytes) scattered in the animal's endoderm. The influx of calcium into nonluminescent endodermal cells through conventional voltage-dependent calcium channels is required for the excitation-luminescence coupling. Our results suggest that the subsequent diffusion of this calcium, via gap junctions, into the neighboring photocytes triggers a localized luminescence response. Following intense stimulation, the local rise in calcium elicits a secondary wave of luminescence that is supported by a voltage-independent calcium permeability mechanism in the photocyte plasma membrane. These two mechanisms for elevating internal calcium in light-emitting cells can account for the spatial and temporal features of intracellular luminescence in Obelia. PMID- 2576213 TI - Glutamate receptor desensitization and its role in synaptic transmission. AB - Responses of excitatory amino acid receptors to rapidly applied glutamate were measured in outside-out membrane patches from chick spinal neurons. The peak current varied with glutamate concentration, with a half-maximal response at 510 microM and a Hill coefficient near 2. Currents activated by 1 mM glutamate desensitized and recovered in two phases. The faster time constant was identical to the time constant of decay of synaptic currents, suggesting that glutamatergic synaptic currents are terminated, in part, by receptor desensitization. Steady state desensitization was evident following application of only 2-3 microM glutamate, concentrations comparable to levels in the extracellular space in the intact brain. Thus, glutamate receptor desensitization can affect synaptic efficacy in two ways: at high concentrations, rapid desensitization of receptors may curtail synaptic currents; at low concentrations, there is a significant reduction in the number of activatable receptors. PMID- 2576214 TI - Specific inhibitors of protein kinase C block transmitter-induced modulation of sensory neuron calcium current. AB - Modulation of neuronal, voltage-dependent calcium current has been described for a number of transmitters and peptides, but the biochemical basis for this phenomenon has not been completely identified. In several cases protein kinase C (PKC) is thought to mediate transmitter inhibition of calcium current; however, a lack of specific PKC inhibitors has hampered a direct physiological test of this idea. We have used the whole-cell, tight-seal configuration of the patch-clamp technique to apply intracellularly two specific PKC inhibitors to the cell bodies of embryonic chick sensory neurons. Both inhibitors, a 17 kd protein purified from bovine brain and a synthetic 13 amino acid "pseudosubstrate" peptide, blocked inhibition of calcium current by either norepinephrine or an exogenously applied PKC activator. These results provide strong evidence that activation of PKC is a prerequisite for the modulation of sensory neuron calcium current by norepinephrine. PMID- 2576216 TI - Rapid tracheal intubation with vecuronium: the timing principle. AB - A method of administration of vecuronium for intubation that allows excellent intubating conditions in 60 seconds after the induction of anesthesia is described. Patients were divided into three groups based on the dose of vecuronium given. These patients were given either 0.10 mg/kg, 0.15 mg/kg, or 0.20 mg/kg of vecuronium intravenously. Intubating doses of vecuronium were given prior to the induction of anesthesia with sodium thiopental. Administration of the sodium thiopental was timed to the onset of clinical weakness in each patient. PMID- 2576215 TI - Cycling of actin assembly in synaptosomes and neurotransmitter release. AB - We have investigated the regulation of actin assembly in whole mouse brain synaptosomes and how that regulation modulates neurotransmitter release. During a 30 s depolarization with high K+, filamentous actin (F-actin) levels, monitored by staining with rhodamine phalloidin, increase dramatically (up to 300% in 3 s), decrease, and increase once again. This F-actin cycling is regulated by pathways both dependent and independent of Ca2+ influx and is markedly affected by exposing synaptosomes to Li+, tetrodotoxin, and diacylglycerol. Measurement of [3H]norepinephrine release from synaptosomes containing entrapped agents that modulate actin assembly (DNAase I or phalloidin) indicates that actin depolymerization is necessary for normal release and that repolymerization limits release. PMID- 2576217 TI - Pharmacodynamic effects of vecuronium: a dose response study. AB - Vecuronium was administered to patients in dosages of 0.1, 0.2, 0.3, and 0.4 mg/kg to determine the clinical efficacy of large doses of vecuronium. Onset times shortened with larger doses up to 0.3 mg/kg. With 0.4 mg/kg, however, there was no significant improvement in onset time and the duration of action became unpredictable and often prolonged. Mean onset times were 172, 138, 106, and 100 seconds for the four groups, respectively. Prolonged duration of action (43, 96, 111, and 174 minutes, respectively) was observed with increasing dosages. Recovery rates for the first twitch response of the train-of-four stimulus from 10% to 25% were similar in all groups. There were no adverse hemodynamic effects secondary to large doses of vecuronium. PMID- 2576218 TI - Characterization of two major populations of lung fibroblasts: distinguishing morphology and discordant display of Thy 1 and class II MHC. AB - We have determined that murine lung fibroblasts are divisible into two major subpopulations based on expression of Thy 1. Twenty-four to fifty-three percent of freshly isolated lung cells displayed Thy 1 and were separated using FACS into Thy 1+ and Thy 1- fractions for morphologic examination. Analysis by electron microscopy revealed that both the Thy 1+ and Thy 1- fractions contained fibroblasts. Freshly isolated lung cells cultured for 2 wk consisted of greater than 95% fibroblasts, with 28 to 49% displaying Thy 1. These cells were sorted by FACS into Thy 1+ and Thy 1- lines that maintained a stable phenotype over many weeks and that were used as a source to obtain stable fibroblast clones. Adherent pulmonary fibroblasts are not phagocytic and lack the markers of macrophages, dendritic cells, B lymphocytes, and T lymphocytes (with the exception of Thy 1). Interestingly, the Thy 1- fibroblasts spread more and contained a more extensive microfilament and microtubule network than did the spindly and often lipid containing Thy 1+ population. Both populations of fibroblasts synthesized collagen. Class I MHC expression was very low on Thy 1+ and Thy 1- fibroblasts, but high levels were displayed after gamma-IFN treatment. Most exciting was the unexpected finding that only the Thy 1- lines and clones displayed class II MHC (Ia) in response to treatment with gamma-IFN. Moreover, only the Thy 1- fraction (gamma-IFN-treated) presented antigen to T lymphocyte clones, an observation that suggests that this subset of cells may be involved primarily in promoting chronic lung inflammation, which is associated with developing fibrosis. Thus, two populations of pulmonary fibroblasts exist, defined by the expression of Thy 1, distinguishing morphology, inducibility for Ia expression, and antigen-presenting function. It should now be possible, using these characteristics, to ascertain the role of pulmonary fibroblast subpopulations in developing fibrosis. PMID- 2576219 TI - Differential inhibition by cyclosporin A reveals two pathways for activation of lymphokine synthesis in T cells. AB - Two pathways for the activation of lymphokine synthesis in murine T cell clones and polyclonal T cell blast populations were identified. One was induced by ligands of the T cell receptor (TCR) and led to high production of GM-CSF, IFN gamma, and IL-3. The other was induced by IL-2 and led to production of lower levels of GM-CSF and IFN-gamma with relatively little IL-3 synthesis. Cyclosporin A (CsA) markedly inhibited TCR-independent production of lymphokine mRNA and protein at concentrations where IL-2-dependent stimulation of lymphokine production and proliferation was unaffected. Stimulation of lymphokine synthesis by phorbol myristate acetate (PMA) and the Ca2+ ionophore ionomycin, or by ionomycin alone, mimicked the TCR-dependent response. PMA on its own was a preferential stimulus for GM-CSF production, but, whereas CsA did not inhibit PMA stimulation of polyclonal T cell blasts, T cell clones displayed a biphasic response in which CsA only inhibited stimulation by high PMA concentrations. The data suggest that Ca2(+)-independent (CsA-resistant) T cell activation induces synthesis of GM-CSF and IFN-gamma but is a poor stimulus for IL-3 production. On the other hand, when Ca2(+)-dependent (CsA-sensitive) pathways are activated by TCR binding or by a Ca2+ ionophore, production of high levels of all three lymphokines can be induced. PMID- 2576220 TI - Use of indium-111 oxine to study pulmonary and hepatic leukocyte sequestration in endotoxin shock and effects of the beta-2 receptor agonist terbutaline. AB - The dynamic behavior of indium-111 oxine-labeled leukocytes was simultaneously recorded in multiple organs during endotoxin shock in sheep. Also, the effects of the beta-2 receptor agonist terbutaline were studied. An experimental protocol was designed to mimic a clinical condition in an intensive care setting as far as possible. The animals were ventilated with 50% oxygen to avoid hypoxemia and were given large amounts of intravenous fluids to reduce adverse effects of hypovolemia. A moderate dose of E. coli endotoxin (10 micrograms/kg bwt) was given by intravenous infusion to 14 adult sheep, seven of them receiving continuous intravenous infusion of terbutaline (20 micrograms/kg/hr) during 4 hr, starting 30 min after endotoxin, when signs of lung injury had developed. The other seven acted as controls. A marked pulmonary and hepatic leukocyte sequestration together with a sharp drop in leukocyte counts in peripheral blood occurred within minutes after start of the endotoxin infusion in both groups. However, no changes were observed in the kidneys or the gut. After 60 min and until the end of the experiment, there was a significantly lower activity in the lungs and in the liver of the animals treated with terbutaline than in the controls (P less than .01). Furthermore, less marked hemodynamic and respiratory alterations occurred in the terbutaline group compared with the controls. This study confirms the results of other investigators showing that significant leukocyte sequestration occurs in the lungs during endotoxemia, but it also demonstrates that leukocytes sequestrate in the liver, although slightly less than in the lungs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576221 TI - Left ventricular volume and function changes during beta-blockade and accompanying atrial pacing. AB - Radionuclide ventriculography was performed at rest and during transoesophageal pacing on nine anaesthetized baboons (Papio ursinus), alternatively with and without administration of a beta-blocker. Left ventricular volumes, cardiac output, and ejection fraction were determined at each heart rate. A gradual decrease in end-diastolic, end-systolic, and stroke volume followed with increasing heart rate, significantly more pronounced under beta-blockade. Cardiac output and ejection fraction showed no significant changes, although tendencies to increase were observed without beta-blockade. Comparisons of these parameter changes were drawn to those previously observed during the first 5 h of septic shock (E. coli). We conclude that the tachycardia present during this phase of shock is not the only contributory factor to cardiac function changes but that other depressant influences prevail as the added effect of the beta-blocker seems to suggest. PMID- 2576222 TI - Characterization of factor XIIIa positive dermal dendritic cells in normal and inflamed skin. AB - The immunocytochemical identification and characterization of indigenous dermal dendritic cells (dermal dendrocytes) using a rabbit polyclonal antibody to clotting enzyme factor XIII subunit A (FXIIIa) was carried out on normal and inflamed human cutaneous tissue. The immunophenotype of FXIIIa positive dendritic cells was analysed with a panel of 18 monoclonal antibodies using immunoperoxidase and double immunofluorescence staining techniques. The antibody against FXIIIa detected highly dendritic dermal cells located particularly in the upper reticular and papillary dermis. Double fluorescence microscopy showed that FXIIIa positive cells were bone marrow derived (HLe-I+) and co-expressed monocyte, macrophage or antigen presenting cell markers (HLA-DR+, LFA-I+, HLA DQ+, OKM5+, Mo I+, Mono-I+, Leu M3+). No labelling was obtained with cell markers for Langerhans cells (CDI), T lymphocytes (CD2), granulocytes (LeuMI) fibroblasts (Te7), intercellular adhesion molecule-I (ICAM-I) or endothelial cells (Factor VIII related antigen). Gamma interferon induced increased expression of HLA-DR and co-expression of ICAM-I on FXIIIa+ dermal dendritic cells in normal skin in organ culture. Moreover, in benign inflammatory dermatoses such as atopic eczema and psoriasis there was an increased number of FXIIIa+, DR+, ICAM-I+ cells in the upper dermis and foci of FXIIIa+ cells in the epidermis closely associated with lymphocytes. FXIIIa positive cells in human skin represent a specific population of bone-marrow dermal dendritic cells, distinct from Langerhans cells, that share some features common to mononuclear phagocytes (monocyte/macrophages). In addition, the detection of HLA-DQ on 48% of FXIIIa+ cells and the lack of OKMI in combination with high OKM5 expression suggests an antigen-presenting cell phenotype. PMID- 2576223 TI - Mullerian inhibiting substance is present in testes of dogs with persistent mullerian duct syndrome. AB - Breeding studies in a strain of miniature schnauzer dogs with Persistent Mullerian Duct Syndrome (PMDS) indicate this syndrome is inherited as an autosomal recessive trait, as it is in man. Testes of neonatal dogs affected with PMDS and normal male littermates were examined for Mullerian Inhibiting Substance (MIS) production by immunohistochemistry and bioassay. MIS immunoactivity was detected in Sertoli cells of normal and affected pups using an avidin-biotin complex-enhanced method. Rat embryonic Mullerian ducts regressed when cocultured with testis fragments of both normal and affected pups in a graded organ culture bioassay, demonstrating that the MIS produced was bioactive. These findings indicate that Mullerian duct persistence in affected dogs is not due to a mutation in the structural gene for MIS, but rather, by inference, to a failure of response to MIS at the receptor level. PMID- 2576224 TI - [Autonomic innervation of the ovaries]. PMID- 2576225 TI - Efficacy and safety of the combination therapy Pilogel/beta-blocker: interim results. AB - The interim results of a multicentered clinical trial with the combination therapy therapy Pilogel/topical beta-blocker (twice daily) in patients with primary open angle glaucoma or ocular hypertension are discussed. Six patients were treated with Pilogel and a topical beta-blocker for one month. Four out of six patients responded well to the combination therapy. Most patients experienced some difficulty in applying the gel and their eyelids stuck together on awakening. In two patients a superficial punctate keratitis was observed. We found an average decrease in intra-ocular pressure (IOP) of 22.5% 22.5 hours after Pilogel administration, but there was some tendency towards higher evening values compared to morning values. In view of the appearance of a corneal haze as described by Johnson et al. during long-term treatment, longer follow-up is necessary. PMID- 2576226 TI - Beta-adrenoceptor blockade in rats enhances the ambulation induced by 5-HT1A receptor agonists. AB - The mixed beta-adrenoceptor and 5-HT1A receptor antagonists, (-)-pindolol and propranolol, enhance rather than inhibit the hyperlocomotion induced in rats by the 5-HT1A receptor agonist, 8-OH-DPAT. The mechanism of this effect was now investigated. The rats were pretreated with the beta-adrenoceptor antagonist or saline and with the agonist 45 min later. Ambulation was quantified as the number of quadrants entered during a 15 min observation period. (-)-Pindolol, alprenolol, betaxolol, ICI 118,551 and a combination of betaxolol and ICI 118,551 (all at 1 mg/kg) significantly enhanced the locomotion induced by 8-OH-DPAT (0.24 mg/kg). Timolol (1 and 10 mg/kg) given 45 min before 8-OH-DPAT was inactive; however, given at 10 mg/kg 15 min prior to 8-OH-DPAT, the compound enhanced locomotion. (-)-Pindolol (1 mg/kg) also enhanced the locomotion induced by the putative selective 5-HT1A receptor partial agonists, flesinoxan and ipsapirone, but not that induced by 5-OH-DPAT, a DA2 receptor agonist. These results suggest that beta 1- or beta 2-adrenoceptor antagonism can enhance the locomotion induced by 5-HT1A receptor agonists. In the case of mixed 5-HT1A and beta-adrenoceptor antagonists, the beta-adrenoceptor-mediated effect may mask the inhibition of locomotion expected from 5-HT1A receptor antagonism. PMID- 2576227 TI - Dopamine uptake by the human platelet: effects of dopamine receptor agonists. AB - The uptake of dopamine by human platelets has been shown to be temperature- and energy-dependent and not to occur as a result of dopamine binding to and then being internalised with the dopamine D-1 or D-2 receptor. However, occupancy of these receptors could affect dopamine uptake by platelets through their second messenger systems. We have therefore studied the effect of dopamine receptor agonists, which stimulate receptor second messenger systems, on dopamine uptake by platelets. Uptake of [3H]dopamine by human platelets was not affected by the dopamine D-1 receptor agonist SKF 38393 or the dopamine D-2 receptor agonists, quinpirole and bromocriptine. In contrast, the uptake of [3H]dopamine was decreased by the mixed dopamine receptor agonists dopamine and 2-amino-6,7 dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN). Furthermore, [3H]ADTN, like [3H]dopamine, was taken up by platelets. In conclusion ADTN, a compound structurally similar to dopamine appears to complete for the dopamine uptake system on the human platelet. Thus, our data further support the hypothesis that a selective dopamine uptake system is present on the human platelet and that this system is not influenced by the dopamine D-1 or D-2 receptor. PMID- 2576228 TI - Comparison of [3H]YM-09151-2 with [3H]spiperone and [3H]raclopride for dopamine d 2 receptor binding to rat striatum. AB - The Kd value of [3H]YM-09151-2, a potent and highly selective dopamine D-2 antagonist, for binding to rat striatum was about 20 pM (half of that for [3H]spiperone and one-fiftieth of that for [3H]raclopride). The Bmax of [3H]YM 09151-2 binding was about 30% higher than that of [3H]raclopride or [3]spiperone. The ratio (bout 3%) of non-specific to specific binding of [3H]YM-09151-2 was smaller than that of [3H]spiperone and [3H]raclopride. The Hill coefficient values of dopamine D-2 antagonists, SCH23390, mianserin and phentolamine for the inhibition of binding of [3H]YM-09151-2 were near 1.0, and their Ki values with [3H]YM-09151-2 were consistent with those for inhibiting [3H]raclopride and [3H]spiperone binding to D-2 receptors. Thus, [3H]YM-09151-2 may be the most suitable ligand for the labelling of dopamine D-2 receptors in the brain. PMID- 2576229 TI - Effects of SCH 23390 on thyrotropin-releasing hormone-induced behaviour in rabbits. AB - The influence of the dopamine D-1 receptor antagonist, SCH 23390, on thyrotropin releasing hormone (TRH)-induced behaviour was assessed in adult male rabbits. SCH 23390 prevented the effects of TRH (100 micrograms i.c.v.), starting at a very low dose (0.01 mg/kg i.v.). This finding seems to indicate that dopamine D-1 receptors are involved in TRH-induced behaviour. PMID- 2576230 TI - Dopamine D-1 and D-2 receptor agonists and antagonists and neuropeptide-induced excessive grooming. AB - The administration of the dopamine D-1 receptor antagonist, SCH 23390, but not of the dopamine D-2 receptor antagonist, sulpiride, suppressed the excessive grooming induced by a new environment or by various neuropeptides. In addition, administration of the dopamine D-1 agonist, SK & F 38393, induced excessive grooming but that of the dopamine D-2 agonist, quinpirole, did not. It is suggested that dopamine D-1 rather than D-2 receptor stimulation is an important mechanism underlying novelty-induced as well as neuropeptide-induced excessive grooming. PMID- 2576231 TI - Excitation of hippocampal neurons by stimulation of glutamate Qp receptors. PMID- 2576233 TI - [Amino acid neuromediators]. PMID- 2576232 TI - [A pharmacological analysis of the anxiolytic action of derivations of benzodiazepine, GABA and beta-carboline in various tests of tension reaction]. AB - In the test of avoidance of an "illuminated platform" and "precarious situation" intraperitoneal administration of derivatives of benzodiazepine, GABA and beta carboline was shown to attenuate anxiety states in rats. The similar effect was also observed at local administration of serotonin and beta-carboline into the median raphe nuclei. At the same time microinjections of GABA, chlordiazepoxide, phenibut and baclofen into this formation of the brain exerted the anxiolytic effect only in the test of an "illuminated platform". Different spectra of the anxiolytic effect of the tested psychotropic agents is suggested to be due to diverse degrees of the involvement of serotoninergic and GABA-ergic systems of the median raphe nucleus in the anxiety states formed by various aversive actions. PMID- 2576234 TI - Activation of CD4-positive T cells by polysaccharide fractions isolated from the Cupressaceae Thuja occidentalis L. (Arborvitae). PMID- 2576236 TI - Search for genes critical for the early and/or late events in carcinogenesis: studies in Xiphophorus (Pisces, Teleostei). AB - Southern blot analyses of the xiphophorine genome with probes specific for 15 viral and cellular oncogenes revealed that only three v-erbB related EcoRI fragments comprising 4.9 kb of a certain X, 11.5 kb of another X, and 6.7 kb of both a Y and a Z chromosome are inherited in parallel with the Tu complex and melanoma formation. They are accessory in the genome, and are highly homologous with each other and with an ubiquitous autosomal 7.5-kb fragment. The latter one is probably linked to the indispensable Tu complex that is postulated to be present in all individuals of Xiphophorus irrespective of whether they possess or lack the capacity to form melanoma in interspecific hybrids. Three restriction fragments, the X-chromosomal 4.9-kb, the Y-chromosomal 6.7-kb and the ubiquitous Tu-nonlinked 5.5-kb EcoRI fragments were cloned and sequenced. The X- and the Y chromosomal fragments show perfect identity in the regions of the putative exons C and D of the EGF receptor gene and minor but significant differences to the putative exon C (exon D not identified) of the Tu-nonlinked fragment of 5.5 kb, indicating that at least two different types of x-erb B genes coding for slightly different EGF-receptors exist in the fish. Northern blot analyses revealed expression of the Tu-linked x-erbB genes (x-gfrB genes) in both transformed and nontransformed tissue, suggesting their essential role in regulation of normal cell proliferation and in carcinogenesis. We conclude that the indispensable x egfrB genes remain unchanged and strictly regulated, while the sex chromosomal accessory x-egfrB genes possibly undergo dramatic changes in structure and/or function (e.g., unscheduled expression, ectopic expression, point mutations, truncation) leading to activation of the oncogenic potential of these genes, which in turn could induce several cellular events involved in the switch from the normal to the transformed state of the cell. In contrast, none of the x-erbA restriction fragments could be assigned to the Tu-complex or to any regulatory gene (R or S). These results, however, do not exclude the existence of a structural and/or functional relation between x-erbA genes and R and S genes. We therefore analyzed x-erbA genes by cloning, sequencing, and expression studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2576235 TI - Genetic markers for oncogenes, growth factors, and cystic fibrosis. PMID- 2576237 TI - ras gene mutations and clonal analysis using RFLPs of X-chromosome genes in myelodysplastic syndromes. PMID- 2576239 TI - Restriction fragment length polymorphism of the c-Ha-ras-1 proto-oncogene as a marker of genome alterations and susceptibility to the development of some human carcinomas. PMID- 2576238 TI - Hematopoietic growth control by the T-cell CD2 determinant is exerted at a pretranslational level. PMID- 2576240 TI - Genetic characterization of a human endogenous retroviral element located on chromosome 18q21. PMID- 2576241 TI - Treatment of cryptorchidism with human chorionic gonadotrophin (hCG) or gonadotrophin releasing hormone (GnRH); reply. PMID- 2576242 TI - Functional studies of stable L cell transfectants expressing intercellular adhesion molecule 1 [ICAM-1]. AB - High molecular weight DNA isolated from human tonsil was transfected into mouse L cells to produce transfectants expressing the human intercellular adhesion molecule [ICAM-1]. The transfected ICAM-1 molecule was highly expressed on the cell membrane and our studies show that the transfected ICAM-1 molecule was a fully functional adhesion protein. All leucocyte subtypes showed specific binding to the ICAM-1 transfectants, their adhesion being inhibited by Fab1 fragments of W-CAM-1 antibody and LFA-1 MoAb (leucocyte function antigen). B cell lines (RAJI, Nalm1) showed the highest degree of ICAM-1 mediated adhesion. Normal lymphoblasts showed comparable levels of binding whilst normal neutrophils (both resting and activated by (N-formyl-methionyl-leucyl-phenylalanine) fMLP) showed the least ICAM-1-mediated adhesion. Despite a significant level of adhesion to ICAM-1 transfectants shown by T lymphoblasts generated in a two way MLR there was no evidence of cytolysis of ICAM-1 transfectants. These studies demonstrate the potential of ICAM-1 transfectants as tools for analysis of the role of ICAM-1 in lymphoid adhesion. PMID- 2576243 TI - Murine Ly-3 restriction fragment length polymorphism and transcript size differences. PMID- 2576244 TI - Use of laparoscopy in children with impalpable testes. AB - Our experience in Manchester using laparoscopy in children with impalpable testes is detailed. Eighty-seven testes were investigated in 77 patients. Of these, 36% had no testes, although in 28% evidence of a vas was found. In those testes which were found, surgery was performed, either orchidopexy or, if positioned high, microsurgery. Orchidectomy was rarely carried out (5 testes only). PMID- 2576245 TI - Serum levels and urinary excretion of mequitazine after a single oral dose. AB - Pharmacokinetics of mequitazine, a recently introduced peripheral H1-histamine receptor antagonist of phenothiazine type, was followed up to 72 h after the single oral dose of 5 mg of the drug to eight fasted healthy volunteers. Each subject was treated thrice with a dosing interval of 15 days or more. Thus all the results were triplicated. Serum mequitazine was measured by mass fragmentography using a gas-liquid chromatograph/mass spectrometer set in the electron impact mode. Urine phenothiazines were determined fluorometrically before and after cleaving phenothiazines from their glucuronide conjugates. Peak concentration of mequitazine in serum was 3.19 +/- 1.70 (s.d.) ng.ml-1, time to peak concentration 5.67 +/- 1.68 h, elimination half-life 45 +/- 26 h, and elimination rate constant 0.018 +/- 0.007 h-1. Only 10.9 +/- 3.3% of the dose appeared in urine in unconjugated plus the glucuronidated form during the first 72 h. About 46% of the urinary phenothiazines were glucuronide conjugates. The results suggested that after the oral administration only low mequitazine concentrations appeared in serum, most of the drug seemed to be deactivated by the extrarenal route, and the kinetic properties of the drug resembled those of several phenothiazines used for psychiatric therapy. PMID- 2576246 TI - Chronopharmacological study of bunazosin hydrochloride in healthy subjects. AB - Bunazosin, an alpha-1 adrenoreceptor blocking agent, was given orally to six healthy subjects in the morning or in the evening in order to examine the time dependent variations in the pharmacological effects of the drug. The study was carried out on four occasions in a placebo controlled cross-over design. No significant change was observed in blood pressure either after the morning or the evening dosage. Finger skin blood flow (FSBF) assessed by laser Doppler flowmetry increased significantly after the morning dosage, but not after the evening trial. The plasma concentration of bunazosin in the morning in general had a tendency to be greater than that in the evening. A significant correlation was observed between the plasma concentrations and the increments in the FSBF. These results indicate that the pharmacological effects of bunazosin are greater following morning dosage. The present study supports the concept that the time dependent differences in the effect of bunazosin are, at least, caused by the time-dependent changes in plasma drug concentration. PMID- 2576247 TI - Gestodene: new clinical perspectives on progestogen efficiency. Proceedings of a symposium held at the XIIth World Congress of Gynecology and Obstetrics. Rio de Janeiro, Brazil, October 1988. PMID- 2576248 TI - Maximizing the clinical benefits of steroidal contraception: an international outlook. Proceedings of a symposium. New York City, October 22, 1988, and Rio de Janeiro, October 26, 1988. PMID- 2576249 TI - Inhibition of ovulation by a new low-dose monophasic contraceptive containing gestodene. AB - Twenty-five healthy women volunteers were selected to evaluate ovulation inhibition by a monophasic oral contraceptive preparation containing 75 micrograms gestodene and 30 micrograms ethinyl estradiol. Each subject participated for eight consecutive cycles, consisting of a pretreatment cycle, six treatment cycles, and a posttreatment cycle. During five explored cycles, serum LH, FSH, estradiol, and progesterone levels were measured daily on cycle days 8 through 17; in addition, progesterone was measured once, around cycle day 21. Pelvic ultrasounds were performed on cycle days 6, 8, 10, 12, 14, and 16. In the 18 volunteers completing the entire study, LH and FSH levels were strongly depressed, in equivalent degree, during the first, third, and sixth treated cycles. From treated cycle days 8 to 17, a significant decline of LH and FSH levels occurred, reaching values on the lower limit of detection. Luteal activity was not detected in any of the treated cycles. Follicular activity, as reflected by estradiol levels, was more strongly depressed during the first treated cycle (first contraceptive pill taken on day 1 of menstruation) than in the third and sixth treated cycles (the first pill taken after a seven-day pill-free interval). The excellent inhibition of follicular maturation was confirmed by ultrasonic assessment of the ovaries. Restoration of ovarian function during the first posttreatment cycle was excellent, showing a midcycle hormonal profile identical to that of the pretrial cycle. PMID- 2576250 TI - The current and future contraceptive needs of Japanese women. PMID- 2576252 TI - The pharmacologic and metabolic effects of oral contraceptives. AB - The oral contraceptive formulations in use today consist of three types. One type has a fixed dose of a combination of a synthetic estrogen and a synthetic progestin, the second has varying doses of each of these steroids, and the third consists of a fixed dose of a progestin without an estrogen. The estrogen in the older formulations contained mestranol, while all those developed since 1974 contain ethinyl estradiol. The estrogen is combined with varying dosages of nine different progestins to produce a wide variety of formulations. The major metabolic effects of the estrogen are an increase in hepatic production of globulins, some of which cause hypercoagulability, and an increase in blood pressure in certain users. By varying HDL-cholesterol, the estrogen has a beneficial effect upon lipids. Other estrogenic effects include fluid retention, depression, and breast tenderness. Most of the progestins have androgenic effects, being derived from 19-nortestosterone. These include peripheral insulin resistance, a lowering of HDL-cholesterol, nitrogen retention, and nervousness. Both the estrogen and progestins metabolic effects are dose-related and with the newer, low-dose formulations, the adverse metabolic and clinical effects are minimal. Thus the results of the epidemiologic studies performed 10 to 15 years ago, when women were using high-dose formulations, are not relevant to the oral contraceptive formulations in use today. Recent epidemiologic studies show that healthy, nonsmoking women using oral contraceptives do not have an increased risk of developing cardiovascular disease. PMID- 2576251 TI - The current status of oral contraceptive clinical development in Japan. AB - Since the oral contraceptive guideline was issued in April 1987, Japanese pharmaceutical firms have been asking physicians to perform clinical studies of the low-dose OCs. At present, eight products from six companies are under clinical development. Ethinyl estradiol (30-35 micrograms per tablet) as an estrogen component is common to all the test drugs. The progestin component in each OC is norethindrone, levonorgestrel, or desogestrel. Phase I clinical studies on small numbers of healthy volunteers showed that they could tolerate the test drugs without any serious complaints. The effects on endocrine systems, including the inhibition of ovulation, were also examined. Pharmacokinetic parameters of active ingredients were comparable to those of Western women, and no substantial difference seemed to exist between Japanese and Western women. As an example, the results of phase I studies of OJK-777 (Ortho-Novum 7/7/7) are mentioned. Phase III clinical studies, which are "open studies," are now under progress with more than 3,000 women. The major objectives are to examine (1) how well the drugs are tolerated, and the dropout rates; (2) the effects on cycle control, especially bleeding patterns; (3) effects on the cardiovascular system, including coagulation and lipid metabolism; (4) effects on hormone secretions. Although some women have been taking the test drugs for more than 12 cycles, overall statistics are not yet available, because the guideline requires long term administration (for more than 24 cycles). However, some characteristic features observed thus far are discussed. PMID- 2576254 TI - Results of oral contraceptive epidemiologic studies regarding neoplastic and cardiovascular effects. AB - Over the past three decades, much of the research on oral contraceptives has focused on cardiovascular and neoplastic effects. Results of recent United States studies have shown no increased risk of death among users of oral contraceptives, although an increased risk of idiopathic venous thromboembolism has been a consistent finding. There is compelling evidence that oral contraceptive use provides significant protection against endometrial and ovarian cancer, and that this protection lasts at least 15 years. In addition, no clear association has been found between oral contraceptive use and breast cancer or cervical cancer. Data on hepatocellular carcinoma and malignant melanoma are inconclusive. PMID- 2576253 TI - A multicenter clinical evaluation of a new monophasic combination: Minulet (gestodene and ethinyl estradiol). AB - The safety and efficacy of a low-dose monophasic oral contraceptive (OC) containing a new progestogen, gestodene (GTD), combined with ethinyl estradiol (EE) is being investigated in two ongoing multicenter trails. In this interim analysis, the formulation was found to be effective and well tolerated. Subject compliance was excellent; no pills were missed in 91.2% of the cycles. The number of women who withdrew from the study was low (15%), indicating good subject acceptance. GTD + EE provided optimal cycle control. Of the total number of OC cycles analyzed, spotting occurred in 8.1%, breakthrough bleeding in 1.8%, and both spotting and breakthrough bleeding in 3.3%. The incidence of spotting decreased fairly steadily during OC administration. Amenorrhea occurred in 0.5% of the cycles. There were no unexpected or serious side effects. The incidence of side effects was low and declined with increased duration of OC use. There were no clinically significant changes in weight or blood pressure. Virtually all of the systolic and diastolic blood pressure readings were in the normal range. The results of this interim analysis indicate that the GTD + EE formulation is a safe and reliable contraceptive. PMID- 2576255 TI - Comparison of two monophasic oral contraceptives: gestodene/ethinyl estradiol versus desogestrel/ethinyl estradiol. AB - The contraceptive efficacy, cycle control, safety, and subject acceptance of the new contraceptive (OC) preparations containing gestodene (GTD) plus ethinyl estradiol (EE) are being compared with the combination containing desogestrel (DSG) plus EE in a randomized, open-label outpatient study. Interim data from six cycles of this ongoing study were obtained for 378 women receiving 75 micrograms GTD + 30 micrograms EE per day and 384 women receiving 150 micrograms DSG + 30 micrograms EE per day. Each group received OCs for 21 days per cycle. There were no pregnancies in subjects receiving either OC during 1,658 cycles of GTD + EE or 1,707 cycles of DSG + EE use. The continuation rates were similar in the two groups, and no major differences in type or incidence of side effects were observed. There were also no clinically significant changes in blood pressure or body weight in either group. Slightly better cycle control was observed for subjects taking GTD + EE, since the incidence of spotting and breakthrough bleeding was slightly greater for women taking DSG + EE. The incidence of amenorrhea (missed periods) tended to be lower for the subjects taking the GTD containing preparation: 7 (0.5%) cycles compared with 12 (0.9%) DSG + EE cycles. The GTD + EE-treated subjects also had a lighter menstrual flow. Fewer subjects taking GTD + EE withdrew because of side effects typically associated with OCs. The data from this study indicate that the new combination of GTD + EE provides safe and effective oral contraception, with good tolerance and cycle control. PMID- 2576256 TI - The effects of oral contraceptives on reproduction. AB - Early reports linking the use of contraceptive steroids to congenital malformations have not been substantiated. There is a delay in the return of fertility after cessation of oral contraceptive use, but this may be concentrated in childless women aged 30 to 34. Oral contraception does not influence the rate of infertility. After the cessation of oral contraceptive use, there is no increase in the incidence of spontaneous abortion in subsequent pregnancies, nor is there an increased risk of pregnancy complications. Women who use oral contraceptives do not breast-feed as long as nonusers, but no differences can be detected between the growth and development of the children of oral contraceptive users and nonusers. There is no relationship between oral contraceptive use and pituitary adenomas, or between oral contraceptive use and subsequent amenorrhea. PMID- 2576257 TI - A clinical overview of a new triphasic contraceptive containing gestodene. AB - In three ongoing open studies conducted by 50 investigators in Europe, South America, and New Zealand, 639 subjects followed a new triphasic regimen of gestodene (GTD) and ethinyl estradiol (EE) for 3,020 cycles. One study used GTD + EE only, but in each of the other two studies a comparator oral contraceptive (OC) also was given: norethisterone (NET) + EE in one and desogestrel (DSG) + EE in the other. The objective of all three studies was to assess the efficacy, cycle control, and safety of the triphasic GTD + EE. The following is a report of the interim results. Statistical analysis was performed only on differences between groups in the incidences of bleeding irregularities. During six treatment cycles, subjects either followed the GTD + EE regimen (50 micrograms GTD + 30 micrograms EE for 6 days, 70 micrograms GTD + 40 micrograms EE for 5 days, and 100 micrograms GTD + 30 micrograms EE for 10 days) or took triphasic NET + EE or monophasic DSG + EE. Each cycle concluded with a seven-day hiatus in study medication. No pregnancies occurred with any of the contraceptive preparations (Pearl Index = 0). Compliance was good in all studies and a majority of subjects were still participants at cycle 6. Normal bleeding was reported during 92% of the total evaluable cycles of GTD + EE use. Cycle control with GTD + EE was superior to that with NET + EE or DSG + EE: Breakthrough bleeding occurred in 1.5% of the pooled GTD + EE cycles versus 6.6% of the NET + EE cycles and 2.6% of the DSG + EE cycles; spotting occurred in 4.5% of the GTD + EE cycles versus 9.7% of the NET + EE cycles and 10.3% of the DSG + EE cycles; and breakthrough bleeding plus spotting occurred in 2.1% of the GTD + EE cycles versus 8.1% of the NET + EE cycles and 4.6% of the DSG + EE cycles. Amenorrhea occurred in 2.0% of the cycles with NET + EE, but was reported by only 0.3% of all the subjects given GTD + EE and 0.7% of those given DSG + EE. Cycle length and intensity of bleeding changed little during the use of any of the study preparations. Mean length of withdrawal bleeding during the GTD + EE regimen shortened from 4.5 days (prestudy) to 4.0 days. With each OC, the subjects' mean weight during cycles 3 and 6 differed less than 0.5 kg from baseline values.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2576258 TI - Cardiovascular effects of oral contraceptives: a review. AB - The evidence for and against the association of oral contraceptives (OCs) with vascular disease is reviewed, along with the possible pathophysiologic mechanisms for such an association, including effects on coagulation, circulating lipoproteins, and glucose metabolism. The new, low-dose estrogen OCs appear to affect coagulation minimally, and anticoagulant as well as procoagulant effects have been documented. Such concomitant factors as cigarette smoking, obesity, a family history of thrombosis, lack of physical activity, and blood type influence coagulation more strongly. Myocardial infarction and stroke are strongly correlated with the levels and pattern of circulating lipoproteins. The estrogen components of OCs have a favorable effect on lipids, while the effect of progestins, particularly potent androgenic progestins, is unfavorable and could be significant. OCs containing high-dose androgenic progestins can produce abnormal glucose tolerance resulting in increased cardiovascular risk. Low-dose OCs are associated with early, transient breakthrough bleeding. However, educating patients in the management of breakthrough bleeding can help reduce the number of women who must be switched to higher-dose OCs. Epidemiologic evidence confirms the safety of low-dose OCs. By selecting patients carefully, the risk of vascular disease from oral contraception can be reduced to very low levels. PMID- 2576259 TI - Metabolic aspects of the new low-dose oral contraceptives. PMID- 2576260 TI - Noncontraceptive clinical benefits of oral contraceptives. AB - The contraceptive benefits of oral contraceptives have become well known since the introduction of this birth control method in the 1960s. Since that time, a more sophisticated understanding of the hormonal components of the medication has developed, along with reduction in the dosages of these hormones. During the past decade in particular, the medical literature has documented a number of noncontraceptive benefits delineated by studies conducted in Europe and the United States. Users of oral contraceptives have reduced rates of both endometrial and ovarian cancer, and this protection persists even when oral contraceptive use is discontinued. The risk of ectopic pregnancy is reduced up to tenfold among oral contraceptive users and the risk of pelvic inflammatory disease (salpingitis), two- to fourfold. The necessity for performing surgical excision of benign breast cysts or functional ovarian cysts is substantially reduced in women who take oral contraceptives. There also is evidence that the risk of rheumatoid arthritis is reduced in oral contraceptive users. Finally, women who take oral contraceptives have less menstrual dysfunction, such as menorrhagia and dysmenorrhea, than do nonusers. In the United States, it has been estimated that as many as 50,000 hospital admissions are prevented annually because of the noncontraceptive benefits of these drugs. Accordingly, these benefits should be taken into account when discussing contraceptive methods with patients. PMID- 2576262 TI - The worldwide use of steroidal contraception. AB - Historically, concerns about rapidly growing populations and resources that could not support them persuaded governments of developing countries to initiate family planning programs. Between the early 1960s and the early 1980s, the number of governments supporting these programs increased from 7 to approximately 120. Today, 52 governments in developing countries provide support to family planning programs because of the demographic rationale, and 65 governments do so because of human rights and health considerations: The effective use of family planning significantly diminishes infant, child, and maternal mortality and morbidity. Forty-five percent of married women of reproductive age worldwide are practicing contraception today; however, 69% do so in East Asia and only 11% in Africa. Female sterilization and use of intrauterine devices are the most popular methods in developing countries, and oral contraceptives and condoms, in developed countries. Of the 400 million women of reproductive age, 140 million (35%) are relying on family planning methods requiring male cooperation and less than 60 million (15%) are using oral contraceptives. More than half of these oral contraceptive users live in four countries: the United States, Brazil, France, and the Federal Republic of Germany. On the other hand, the percentage of currently married women, aged 15 to 19 years, who have never used any form of contraception is as high as 85% to 90% in Bangladesh, Sudan, and Pakistan. In many developing countries, there is a statistically significant correlation between women's use of contraception and years of education. Other important factors influencing contraceptive prevalence include the established or perceived side effects of currently available methods, the status of women, the political climate, and a number of behavioral and social determinants. PMID- 2576263 TI - Epidemiologic studies of oral contraception. AB - Epidemiologic studies of oral contraception are of two main types: case-control and cohort. The best known cohort studies are the Royal College of General Practitioners' study and the Oxford-Family Planning Association study, both of which have been conducted in the United Kingdom. Combination oral contraceptives- both the older, higher-dose type, and the newer, lower-dose type--are highly effective if used properly. Noncontraceptive benefits of combination oral contraceptives include protective effects against menstrual disorders, anemia, benign breast disease, functional ovarian cysts, ovarian cancer, endometrial cancer, pelvic inflammatory disease, and uterine fibroids. Adverse effects include various cardiovascular problems, liver tumors, and the temporary impairment of fertility after stopping use, especially in older, nulliparous women. Effects, if any, on breast cancer and cervical cancer are still under evaluation. The often quoted cardiovascular risks of combination oral contraceptives are derived from studies of the older, higher-dose pills used in an outmoded way. There is evidence that modern pills, used by properly selected young women who are subsequently kept under surveillance, carry a minimal cardiovascular risk. A national study is currently in progress in the United Kingdom to try to confirm this. PMID- 2576261 TI - Effect of two monophasic oral contraceptives containing gestodene or desogestrel on serum lipoprotein lipid levels. AB - Forty-nine healthy women aged 20-35 years who had not been pregnant or using an oral contraceptive (OC) for the previous 3 months were randomized into two groups, one group taking an OC containing 75 micrograms gestodene (GTD) and 30 micrograms ethinyl estradiol (EE), and the other group using an OC with 150 micrograms desogestrel (DSG) and 30 micrograms EE. Fasting blood samples were taken before treatment, and after cycles 3 and 6, between the 18th and the 22nd day of the cycle. Blood lipoprotein lipid levels were measured. Serum total cholesterol did not change significantly in both groups. However, in the first three cycles, serum triglyceride increased by 46% and 40% and HDL-cholesterol by 14% and 8% in the GTD and DSG groups, respectively. The serum LDL level decreased by 6.2% and 11.8%, respectively. Between the third and sixth cycle, no further significant changes were observed, nor did these changes differ significantly between the two groups. In conclusion, both OC preparations exerted small and probably favorable effects on serum lipoprotein lipid levels. PMID- 2576264 TI - Effects of oral contraceptives on circulating lipids and lipoproteins: maximizing benefit, minimizing risk. PMID- 2576265 TI - The importance of the worldwide contraceptive experience ot Japanese physicians. AB - Oral contraceptives (OCs) have been used by more than 50 million women worldwide. About 30 years ago, Japan also wished to develop and introduce oral contraceptives. Regrettably, the government was not supportive. As a result, Japanese women have not had access to this form of contraception. After two years of intensive discussions at the Special Committee level, the Japanese Ministry of Welfare (KOSEISHO) published guidelines in 1987 to allow clinical trials of oral contraceptives to begin. This article discusses the relevance and importance of the worldwide experience with oral contraceptives to the Japanese physician. Despite the long wait, the Japanese physician looks forward to being able to apply clinically what has been learned worldwide. PMID- 2576266 TI - Noncontraceptive health benefits and risks of steroidal contraception. PMID- 2576268 TI - Community health representatives: a valuable resource for providing coronary heart disease health education activities for Native Americans. PMID- 2576267 TI - Long-acting steroidal contraception: an update. AB - Long-acting, injectable contraceptives first became available in the 1960s. It is currently estimated that almost 3.5 million women are now using depo medroxyprogesterone acetate (DMPA); 800,000 are using norethindrone enanthate (NET-EN), and another few hundred thousand are using a variety of once-a-month injectables comprised of progestin plus estrogen. The advantages of injectable contraceptives are that they are highly effective, independent of coitus, easily administered, and they ensure regular contact with health services personnel. The last factor may be considered a disadvantage by some, since contact is more frequent than would be required for routine health services. The major disadvantage of the progestin-only formulations is disruption of normal menses, giving rise to unpredicted episodes of bleeding and spotting. With the once-a month formulation, on the other hand, there are few discontinuations due to disruption of menses. For a long-acting method to be used longer than 6 months, it is desirable to choose an implant, since the method can be discontinued at will. The first implant system to be developed was Norplant, a set of six rubber capsules filled with levonorgestrel and implanted under the skin. The implant releases sufficient levels of medication to protect against pregnancy. For the first 5 years, the average failure rate was four or five per thousand users per year. The failure rate for women using standard oral contraceptives is approximately 20 to 50 per thousand. The most common side effect of the implant method is the disruption of the menstrual cycle, an effect that is particularly marked in the first month of use.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576269 TI - Analysis of benzodiazepines and tricyclic antidepressants in serum using a common solid-phase clean-up and a common mobile phase. AB - A single, rapid and specific solid-phase clean-up procedure was developed for the analysis of benzodiazepines and tricyclic antidepressants using a carefully selected wash step and specific sequential elution. Benzodiazepines were eluted from the solid-phase column using as mixture of water-methanol-acetonitrile (2:3:3) followed by the elution of tricyclic antidepressants with methanol containing 0.6% diethylamine. A 30% solution of acetonitrile in phosphate buffer containing dimethyloctylamine was used as a common isocratic mobile phase for the analysis of benzodiazepines and tricyclic antidepressants on a reversed-phase column and detection was carried out at 242 nm. The sensitivity limit of the assay for benzodiazepines and tricyclic antidepressants was 25 ng/ml in serum with recoveries of 95-105% for benzodiazepines and 76-95% for tricyclic antidepressants. The results were linear for benzodiazepines over the range 50 2000 ng/ml and for tricyclic antidepressants over the range 25-500 ng/ml. Analysis for benzodiazepines and tricyclic antidepressants gave good precision, with a coefficient of variation of less than 5.0%. The method described here will be suitable for use in a clinical setting, where there is a concomitant use of benzodiazepines and tricyclic antidepressants. PMID- 2576270 TI - Quantitative gas chromatographic-mass spectrometric analysis of acrivastine and a metabolite in human plasma. PMID- 2576271 TI - Modification of spino-bulbar autonomic cholinergic systems by activation of alpha adrenergic receptors. AB - Intrathecal (i.t.) injection of neostigmine was employed to activate spinal cholinergic neurons mediating a hypertensive response in freely-moving rats. Our earlier studies have demonstrated that stimulation of central alpha-adrenergic receptors inhibits the pressor response following inhibition of brain cholinesterase. Clonidine (0.5-5 micrograms) pretreatment by i.t. injection did not alter the magnitude of the pressor response to i.t. injection of neostigmine, but did significantly delay the onset of the response. Since systemic administration of clonidine abolished the pressor response to i.t. neostigmine, clonidine was administered by the intracisternal (i.c.) route to determine whether higher centers mediated the inhibitory response. In this situation, clonidine pretreatment significantly inhibited the pressor response to i.t. injection of neostigmine. I.t. injection of norepinephrine (1-10 micrograms) was more effective, but i.c. pretreatment less effective than clonidine in inhibiting the pressor response to i.t. neostigmine. In order to confirm the ascending nature of the spinal cholinergic system, hemicholinium-3 was injected i.c. to deplete medullary levels of acetylcholine. Carbachol was then injected i.t. (since carbachol is a direct-acting agonist, it is not affected by local depletion of acetylcholine). Depletion of medullary acetylcholine significantly blocked the pressor response to i.t. injection of carbachol. These findings are consistent with the concept of an ascending spinal cholinergic pressor pathway. The pressor response to activation of spinal cholinergic receptors is not sensitive to local injection of clonidine, but, the medullary cholinergic component of the system is inhibited by alpha-receptor stimulation. PMID- 2576272 TI - Use of the subcutaneous tissue expander for delayed primary closure of flaps. AB - Two cases of deforming, painful scars on the dorsum of the foot are presented. Simple excision and primary closure of these wounds was not possible. Subcutaneous tissue expanders were implanted proximal to the scar and inflated gradually. Once adequate expansion was obtained, the expanders were removed, and scars excised. Closure was obtained by a pedicle and rotational advancement flap, without stress on the skin over the defect. A discussion of the indications, techniques, and pitfalls of tissue expansion is provided. PMID- 2576274 TI - Diagnostic imaging of trauma to the ankle and foot: Part II. PMID- 2576273 TI - One-stage treatment of gunshot wounds. AB - Delayed primary closure has been advocated for the treatment of gunshot wounds owing to the fact that they are highly contaminated. The authors believe that with meticulous debridement, contaminants are removed; thus, early wound coverage with meshed split-thickness skin graft allows for drainage along with faster healing of all tissues. Split-thickness skin excision was found to be a useful procedure in the immediate management of gunshot injuries. PMID- 2576275 TI - Podiatric imaging quiz. PMID- 2576277 TI - [Role of neuropeptides]. PMID- 2576276 TI - Selective linkage of beta-adrenergic receptors to functional responses in developing rat lung and liver: phosphatidic acid phosphatase, ornithine decarboxylase and lung liquid reabsorption. AB - Neurotransmitter receptors may exhibit transient linkage to specific developmental processes involved in physiological adaptation to extrauterine life and in cell maturation. We have examined the responsiveness of the developing rat lung to beta-adrenergic agonists, using fluid reabsorption, phosphatidic acid phosphatase (an enzyme involved in surfactant synthesis) and ornithine decarboxylase (an enzyme related to cellular development) as markers of these activities. The ability of beta-adrenergic agonists to stimulate phosphatidic acid phosphatase and to cause liquid reabsorption first appeared just before birth, a period in which few receptor binding sites are present; the reactivity of both these processes declined after birth, but the enzymatic stimulation reached a second peak of response during the second and third postnatal weeks. The ability of beta-adrenergic challenge to elicit stimulation of lung phosphatidic acid phosphatase then declined into adulthood, despite the fact that receptor binding sites are increasing during the same period. Lung ornithine decarboxylase activity was poorly linked to beta-receptors in the immediate perinatal period and reached a peak of reactivity during the late postnatal period in which the coupling to phosphatidic acid phosphatase was lost. The pattern for phosphatidic acid phosphatase and liquid content was selective for the lung, as no stimulatory effects were seen for these variables in the liver, despite the comparable beta-adrenergic effects on ornithine decarboxylase in the two tissues. These data suggest that, during development, the coupling of receptors to specific cellular events is more important than the number of receptor sites in determining the pattern of physiological and cellular responses mediated by neurotransmitters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576278 TI - [Growth hormone--physiological roles of endogenous GRF and SRIF]. PMID- 2576279 TI - Inhibition of adenylate cyclase in bovine ciliary process and rabbit iris ciliary body to alpha 2-adrenergic agonists. AB - Alpha 2-adrenergic inhibition of adenylate cyclase in bovine ciliary processes and rabbit iris ciliary body (ICB) was studied. With bovine ciliary process membrane, it was found that cAMP production in the presence of 1 microM isoproterenol was increased with increasing NaCl concentrations from 0 to 200 mM. Clonidine, an alpha 2-adrenergic agonist, produced a NaCl concentration-dependent inhibition of cAMP production in the presence of isoproterenol with a maximum inhibition at 200 mM NaCl (P less than 0.05). NaCl concentrations had no effect on basal adenylate cyclase activities and activity in the presence of clonidine alone. The alpha 2-adrenergic agonists, lofexidine, clonidine and p-amino clonidine were tested for their ability to inhibit isoproterenol-stimulated adenylate cyclase in bovine ciliary process membrane in the presence of 200 mM NaCl. Their dose-response curves showed that they had similar IC50's but the maximum inhibition differed among these agonists. Clonidine was found to be a partial agonists producing 55% of the inhibition obtained with lofexidine. The specificity of inhibition of isoproterenol-stimulated adenylate cyclase by alpha 2-agonists and blockade by pertussis toxin was examined by adenine labelling in rabbit ICB. The results demonstrate that alpha 2-adrenergic receptors exert specific inhibitory effects on adenylate cyclase activity in rabbit ICB, which are mediated by an inhibition guanine nucleotide regulatory protein, Gi. PMID- 2576280 TI - [A familial case of multiple endocrine neoplasia (MEN IIb). Diagnosis of medullary thyroid cancer]. AB - The familial observations of multiple endocrine neoplasia are rare such that there are only four known cases in France. In our family, two children and their mother are affected. Their mother, at the age of 16, was operated on a medullary thyroid cancer (MTC) and now presents with a phaeochromocytoma. Vanessa also presents with a MTC but without either phaeochromocytoma nor hyperparathyroidism. Her sister was then systematically screened and the only positive test was Pentagastrin. This allowed us to practice a thyroidectomy which will confirm the presence of a medullary thyroid cancer. In all three cases, the Marfan-like features, the abnormal facies and lingual neuromas are all features of the disease. These observations are of interest for the systemic familial screening of MTC by tumour markers (calcitonin, ACE) and by the Pentagastrin test, while awaiting for the use of specific probes on chromosome 10. PMID- 2576282 TI - British Pharmaceutical Conference 1989. Science proceedings. 126th meeting, Keele, September 11-14, 1989. PMID- 2576281 TI - [DNA amplification in the study of polymorphisms linked to the cystic fibrosis gene]. AB - The highly specific polymerase chain reaction recently described can be used to amplify selectively several polymorphic regions of DNA genetically close to the cystic fibrosis gene. This method, providing automated, revolutionizes the classical methods of prenatal diagnosis and carrier detection. PMID- 2576283 TI - [Identification of the metabolites of an antiallergic agent, 1-(2-ethoxyethyl)-2 (hexahydro-4-methyl-1H-1,4-diazepine-1-yl)-1H- benzimidazole difumarate (KG 2413), in rats]. AB - The urinary and biliary metabolites of a new antiallergic agent, 1-(2 ethoxyethyl)-2-(hexahydro-4-methyl-1H-1,4-diazepine-1-yl)-1H-b enzimidazole difumarate (KG-2413) in rats were identified by using a 14C-labelled drug and instrumental analyses, e.g., high performance liquid chromatography, gas chromatography (GC), 1H nuclear magnetic resonance, mass spectrometry (MS) and GC/MS. A slight amount of KG-2413 free base was detected only in the unconjugated fraction of urine. The main pathways of biotransformation of KG-2413 in rats were: (a) aromatic hydroxylation in the benzimidazole ring, (b) N-oxidation and N demethylation in the 1,4-diazepine ring, (c) alpha-carbon oxidation (lactam formation) in the 1,4-diazepine ring (d) O-deethylation in the N-ethoxyethyl side chain. Regioselectivity was observed for aromatic hydroxylation, as only two of the four possible monohydroxylated metabolites could be detected. Furthermore, N oxidation and lactam formation reactions were found to be regiospecific, that is, the former took place only at the position of 4-N atom and the latter at 5-C atom, respectively. PMID- 2576284 TI - Aortitis syndrome (Takayasu's arteritis) associated with systemic lupus erythematosus. AB - Nine cases of the aortitis syndrome associated with systemic lupus erythematosus (SLE) have been reported. We describe a 10th case of this unusual association. Our patient was the oldest of any reported and the only one in whom SLE developed before the onset of the aortitis syndrome. PMID- 2576285 TI - Evaluation of the nephrotoxicity of aromatic nitro-amino compounds by urinary enzyme activities. AB - Nephrotoxicity of some aromatic nitro-amino compounds were evaluated by urinary enzyme activities and renal histopathological changes. Male Fischer 344 rats were intraperitoneally injected with aniline, p-aminophenol, acetyl-p-aminophenol, p chloroaniline, p-chloronitrobenzene, p-anisidine, or p-nitroaniline at 1.0 mmol/kg. In the rats injected with p-aminophenol, necrosis of renal tubular epithelial cells and remarkable elevation of urinary N-acetyl-beta-D glucosaminidase (NAG) and gamma-glutamyltranspeptidase (gamma-GTP) activities were observed. Injection with p-chloroaniline caused significant elevation of the urinary NAG and gamma-GTP activities. p-Anisidine and p-nitroaniline induced swelling of the tubular epithelial cells and a significant elevation in urinary NAG activities in rats, which was also caused by p-chloronitrobenzene. However, administration of aniline or acetyl-p-aminophenol did not change either the urinary enzymes or renal histopathology. These results indicate that p aminophenol is a highly nephrotoxic substance, and that nephrotoxicity of p chloroaniline, p-chloronitrobenzene, p-anisidine and p-nitroaniline exceed that of acetyl-p-aminophenol which has been known to cause a renal damage. PMID- 2576286 TI - Noninfectious anterior uveitis in patients infected with human T-lymphotropic virus type I. AB - A consecutive series of 34 patients with HTLV-I-associated myelopathy (HAM), a neurological disease associated with human T-lymphotropic virus type I (HTLV-I), were studied with reference to endogenous ocular disorders. These patients were examined at the Kagoshima University Hospital between 1986 and 1988. Five of the 34 HAM patients showed noninfectious, granulomatous anterior uveitis responding to corticosteroid therapy and/or retinal microvascular changes such as isolated cotton-wool spots; one of the patients had recurrent uveitis. Additionally, twelve of 30 patients who had been infected with HTLV-I but remained healthy systemically had ocular manifestations similar to those in HAM patients were included in this study. The ocular lesions in these patients were not explained by any established disorders that manifest uveitis or retinal microangiopathy. Some of the HTLV-I-seropositive patients with ocular disorders showed antibodies against HTLV-I in the aqueous humor. This might have resulted from diffusion of serum antibodies through a damaged blood-aqueous barrier or local synthesis of antibodies. The HTLV-I infection might be primarily responsible for a certain form of endogenous anterior uveitis that has remained hitherto etiologically undefined. PMID- 2576287 TI - Psychosis of epilepsy--an approach to a biological basis for postictal and interictal psychoses. AB - Postictal and interictal changes in behavior and the corresponded neurochemical data in the kindling model of epilepsy are reviewed briefly to explore a biological base for epileptic psychosis. Kindling can be a potent animal model to study this problem. A possible participation of both TRH and opioid system in prolonged postictal behavior disorder and of TRH, mesolimbic system and/or PI response to excitatory amino acid in interictal behavior disorder are discussed. A further experimental study is required to disclose the basic mechanism of epileptic psychosis. PMID- 2576288 TI - Effectiveness of bromazepam in children with complex partial seizures. PMID- 2576289 TI - [Familial spontaneous pneumothorax in three siblings including identical twins]. AB - Two identical twin brothers and their sister who suffered from spontaneous pneumothorax (ages at onset, 18, 22 and 20 years) were admitted to our hospital. Their symptoms and clinical courses were similar and all three were finally treated by thoracotomy. No other members of their family had any history of spontaneous pneumothorax. None of these cases presented any abnormal level of serum ACE or alpha 1-antitrypsin. In order to establish the monozygosity of the brothers more accurately, we examined restriction fragment length polymorphisms (RFLPs) which were shown as the band patterns of hypervariable minisatellite regions in human genomes. However there have been few reports of spontaneous pneumothorax in identical twins, but the onset of the disease tends to be the same as in our cases, suggesting a genetical background of spontaneous pneumothorax. PMID- 2576290 TI - [Anti-bacterial defense mechanism of the urinary bladder. Role of mannose in urine]. AB - Bacterial adherence to mucosa is thought to be an initial and important stage to cause urinary tract infection. Among some mechanisms of bacterial adherence, the role of fimbriae and its receptor is worthy of notice. In particular, type 1 fimbriae, for which mannose is assumed as a receptor, is reported as the most common type and called "common fimbriae". Therefore if a certain amount of mannose is present in urine, it will cover the fimbriae of bacteria and competitively block the bacterial adherence to bladder mucosa. As the first step, we tried to detect mannose in urine by high performance liquid chromatography (HPLC). Sugar can be measured by detecting the fluorescence which is produced by a sugar separated by ion exchange, reacting with arginine at high temperature. The results using standard sugar samples should have highly stable retention time and concentration curve with the minimum detectable mannose concentration of 0.02 microgram. We investigated mannose in urine from 186 cases. Since the mannose peak was often masked by near unidentified peaks, the peak of mannose could be detected only in 80 cases and its concentration could be measured only in 24 cases. Mannose concentration in the urine of the 24 cases was between 2.6 and 108.7 micrograms/ml and in most of cases it was lower than 20 micrograms/ml. Secondary, we examined the possibility of a mannose in urine to prevent bacterial adherence to mucosa by the hemagglutination test using guinea pig erythrocytes and type 1 fimbriated E. coli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576291 TI - [Significance of lipid peroxidation in the pathogenesis of hemorrhagic fever with nephrotic syndrome]. AB - Lipid peroxidation as shown by plasma levels of malonic dialdehyde and acyl hydroperoxides was studied in 92 patients with hemorrhagic fever with renal syndrome (HFRS). It was found that intensity of lipid peroxidation rose and reached maximum values in severe course of the disease. This phenomenon and causes underlying it are under discussion. Disturbances in lipid peroxidation in HFRS patients may play a role in the genesis of pathophysiological processes observed in the above patients including DIC syndrome. In addition, the authors consider prognostic relevance of the recorded shifts. PMID- 2576292 TI - [Use of adrenergic blockaders for correction of pulmonary functions in the treatment of acute cholecystitis]. AB - The assessment of external respiration during a 2-day management of acute pain attack produced by cholecystitis disclosed a 1.2-1.5-fold decrease in the parameters of the function resultant from poor ventilation of the pulmonary zones and loss of coordination between the ventilation and relevant blood flow. On day 3 of the attack treatment of external respiration returned to normal functioning though in patients over 60 this return took a week, as they had a 1.2-2-fold drop in the blood flow and pulmonary ventilation. The attempts of administration of adrenoblockers in combined treatment of acute cholecystitis succeeded in restoration of pulmonary function during 3 days and in more rapid attenuation of attacks in acute cholecystitis. PMID- 2576293 TI - [Characteristics of neurohumoral regulation in combined lesions of the esophagus, stomach and duodenum]. PMID- 2576294 TI - [Protective function of the skin]. AB - This paper reviews published data concerning the protective function of skin and discusses factors that may affect its bactericidal capability, including space flight factors that are known to reduce its protective effect. Various concepts of the mechanisms of the bactericidal function are discussed. It is shown that in an enclosed environment the species composition of the resident autoflora and pH value of the skin of an essentially healthy man may change. The qualitative composition of the water-oil film as a source of nutrition and a skin microflora environment is discussed. Its effect on the autoflora composition and localization in various skin areas and, consequently, on the bactericidal capability of different skin areas is described. The skin bactericidal function results from an interaction of various factors that should be taken into consideration when developing flight-oriented hygienic requirements because space flight induces changes in the skin status. PMID- 2576295 TI - Epidermal growth factor receptors in breast cancer: association with early relapse and death, poor response to hormones and interactions with neu. AB - Epidermal growth factor receptors (EGFRs) were measured in 221 primary breast cancers by ligand binding with 125I-labelled EGF, and high-affinity sites were quantitated. There was a highly significant inverse relationship between oestrogen receptor (ER) and EGFR (15 EGFR-positive [EGFR+]ER+ and 92 EGFR negative [EGFR-]ER+: 54 EGFR- ER- and 60 EGFR+ ER-). The relapse-free survival and overall survival were significantly shorter for EGFR+ vs EGFR- tumours (P less than 0.001) by about 2 yr in the case of relapse-free survival. When ER- tumours were substratified by EGFR status, the EGFR- ER- tumours had a prognosis almost as good as the ER+ tumours. In 31 of 184 cases, high expression of neu, correlating with amplification, was found. Expression of neu conferred similar poor prognosis to EGFR expression in all prognostic subgroups. Coexpression of neu and EGFR had an additive adverse effect. Epidermal growth factor receptors (EGFR) and oestrogen receptors (ER) were analysed in 221 patients with primary operable breast cancer by means of radioligand assays. After median follow-up of 24 months (range 3-60 months), there had been recurrences in 99 patients, of whom 72 (median age 56 yr, range 32-77 yr) received tamoxifen alone as first-line treatment for recurrence. 14 patients (19%) showed a response to this therapy and 58 (81%) did not. Of 32 ER+ tumours, 12 (37.5%) showed an objective response to tamoxifen compared with only 2 of 40 (5%) ER- tumours (P less than 0.005). Of 35 EGFR+ tumours, 3 (8.5%) achieved an objective response compared with 11 of 36 (30%) EGFR tumours (P less than 0.05). Only 1 of 28 EGFR+, ER- tumours achieved an objective response. Including patients whose disease remained stable for more than 6 months with the responders, however, EGFR status was a better predictor of response to tamoxifen; 15 of 37 EGFR- patients and 5 of 35 EGFR+ patients responded (P less than 0.01). PMID- 2576296 TI - Multiple sites of action of the vitamin D endocrine system: FSH stimulation of testis 1,25-dihydroxyvitamin D3 receptors. AB - 1,25-Dihydroxyvitamin D [1,25(OH)2D] receptors exist in numerous unexpected tissues. These include, for example, rat lung, heart, testis, and uterus, but not prostate and bladder. The issues of 1,25(OH)2D effects on and receptor location in the testis were addressed by (a) physiological and pharmacological manipulations of tubule cell types and (b) histological examination of testes of vitamin D-deficient rats. FSH treatment in hypophysectomized adult rats increased 1,25(OH)2D receptor levels by 135% (P less than 0.01). Busulfan treatment reduced testis receptor levels by 35% (P less than 0.05) after 35 days (maximum effect), and the effect was reversed after recovery (85 d). Cryptorchidism for 5 or 50 days resulted in modest (33%, P less than 0.05) or substantial (79%, P less than 0.001) reductions in receptor levels. Only the FSH treatment and 50 days cryptorchidism reduced receptor levels in the residual tissue. The testes of vit. D-deficient rats showed incomplete spermatogenesis and degenerative changes. Although interpretation is complicated by the intricate communication among testis cell types, these data suggest that the Sertoli cell is a primary site of action of 1,25(OH)2D in the testis. Moreover, these data indicate that 1,25(OH)2D receptor function in the testis relates to germ cell division/maturation, although this may be an indirect effect via the Sertoli cells. PMID- 2576297 TI - Testicular steroid sulfatase in a cryptorchid rat strain. AB - Steroid sulfatase (STS) activity was studied in scrotal and abdominal testes from genetically unilateral cryptorchid rats. Specific STS activity was significantly increased in microsomes from abdominal and scrotal testes of the cryptorchid animals as compared to that of control ones. When expressed per gonad, STS activity was only enhanced in the scrotal testis. No difference in the enzyme affinity was observed between descended and undescended testes. Testosterone content was markedly reduced in the abdominal testes. Normal plasma testosterone levels together with elevated LH levels were measured in the cryptorchid rats. The existence of differences in STS expression between descended and undescended testes gives additional support for this enzymatic activity being implicated in testicular function. PMID- 2576298 TI - Effects of several neuroleptics, antidepressants and monoamine uptake blockers on ATPase activity and related oxygen uptake in rat brain in vitro. AB - An experimental trial was conducted to study the effects of phenoxybenzamine, cocaine, carbamazepine, loxapine, clozapine, clothiapine, thiothixene, droperidol, alprazolam, imipramine, maprotiline, dibenzepin, nomifensine, trazodone, mianserin, viloxazine, doxepin and amoxapine on photocolorimetrically rated ATPase activity and on related oxygen uptake, determined by manometrical means, within a concentration range of 0.1-0.001 mM. Phenoxybenzamine, clothiapine and maprotiline at 0.1 mM inhibited sodium-potassium ATPase activity and related QO2 by 30-40%. Loxapine, trazodone, amoxapine and alprazolam at 0.1 mM inhibited sodium-potassium ATPase activity by 25-35%. Imipramine, nomifensine and droperidol at 0.1 mM inhibited QO2 by 20-35%. Cocaine, at all concentrations assayed, inhibited ouabain insensitive ATPase. The remaining drugs did not produce significant modifications. PMID- 2576299 TI - Pharmacokinetics of falintolol II. Absorption, distribution and elimination from tissues and organs following ocular administration and intravenous injection of falintolol in albino rabbits. AB - The absorption, distribution and elimination of falintolol maleate was studied in various ocular and extraocular tissues and organs following ocular instillation, intravenous injection of a 0.5% 14C-falintolol ophthalmic solution and repeated ocular instillations of a 1% non-labeled falintolol ophthalmic solution into albino New Zealand rabbits. Falintolol was distributed in all studied tissues and organs after both routes of administration. After ocular instillation, levels of total radioactivity were distinctly higher in ocular tissues than after intravenous injection. Thus, the level was 475 times more important in cornea, 72 times in aqueous humor and 36 times in iris and ciliary body after ocular instillation. On the other hand, levels of total radioactivity in extraocular tissues and organs were 30-50% higher after intravenous injection compared to ocular instillation of the same dose. Peak levels of total radioactivity were generally achieved between 30 min and 1 h after ocular instillation, while 1.5 h after intravenous injection an increase in the declining part of the curve occurred. This increase, characteristic of an enterohepatic reabsorption, was also observed in blood and plasma 1 h after intravenous injection. Urinary elimination was the major means of excretion since 79.6% of total radioactivity was found in urine 6 h after intravenous injection and 74.5% 12 h after ocular instillation. But after ocular instillation, only 5% was excreted as unchanged falintolol. Whatever the route of administration, after single or repeated application, no drug accumulation was evident. PMID- 2576300 TI - [Anti H2 receptors and perforated peptic ulcer. Review of 442 cases]. AB - H2 blockers have accelerated the reduction in elective peptic ulcer surgery but appear to have had no equivalent effect on the incidence of perforated ulcer success. A 13 year (1975-1987) review of perforated peptic ulcer is presented. The mean annual number of operations for perforation fell from 8.21% to 4.93% after 1980, while the number of operations for perforated gastric ulcer in this period was almost unchanged. A significant reduction was found in mean annual rates for perforated duodenal ulcer from 6.86% to 3.82% after 1980, while the number of operations for perforated gastric ulcer in this period was almost unchanged. PMID- 2576302 TI - Influence of inducers and inhibitors on the metabolism in vitro and neurochemical effects in vivo of MDMA. AB - (S)-(+)- and (R)-(-)-3,4-methylenedioxymethamphetamine (MDMA) were metabolized in vitro by rat liver microsomes via N-demethylation to 3,4 methylenedioxyamphetamine (MDA). Whereas no difference was found in the biotransformation of the two enantiomers in the male rat or in the phenobarbital (PB) treated animals of either sex, more than twice as much MDA was formed from (S)-(+)- than from (R)-(-)-MDMA in the untreated female rat. Although 3 methylcholanthrene (3MC) pretreated rat liver microsomes were less active than those from the untreated rats of the same sex, they formed more MDA from (+)- than from (-)-MDMA. The enantioselective metabolism thus appears to be associated with the relative abundance of individual cytochrome P-450 isozymes. (S)-(+)- and (R)-(-)-MDMA.HCl (20 mg/kg) were about equipotent in depleting serotonin (5-HT) levels in the frontal cortex at 3 hrs and 1 wk following oral administration to female rats. Pretreatment of rats with SKF-525A attenuated and that with PB enhanced the 5-HT depleting potential of either isomer at 3 hrs. The 5-HT depleting potency of (+)-MDMA was significantly greater than that of its (-) antipode at 3 hr in PB pretreated, but not in SKF-525A pretreated animals. The results suggest that the neurochemical effects of MDMA are caused by the formation of an active metabolite in vivo, and since both enantiomers were N demethylated in vitro to approximately the same extent by PB pretreated rat liver microsomes, the active metabolite may be other than MDA. PMID- 2576301 TI - Effects of gestational exposure to phencyclidine: distribution and neurochemical alterations in maternal and fetal brain. AB - Phencyclidine is a widely used drug of abuse and is known to produce a wide variety of psychoactive effects. PCP abuse by pregnant women has been reported to result in the birth of infants exhibiting irritability, jitteriness and hyperactivity with high pitched cries. The present study was designed to evaluate the distribution of PCP in the maternal and fetal brain and the neurochemical effects produced by gestational exposure. Pregnant Sprague-Dawley rats were treated sc with 5 mg/kg PCP on 3 consecutive days (GD 9-11, 12-14, 15-16, or 18 20). On gestational day (GD) 21 all rats were killed by decapitation and maternal and fetal blood was collected for PCP analysis. Brains were dissected from dams and fetuses for PCP and neurochemical analyses. On GD 21 after exposure on GD 18 20, the fetal: maternal ratio of brain PCP concentrations was 11:1. PCP exposure on GD 12-14, 15-17, and 18-20 significantly decreased fetal brain PCP binding sites on GD 21, whereas maternal values were unchanged. Fetal dopaminergic and muscarinic cholinergic receptor binding and neurotransmitter concentrations were unaffected by prenatal PCP exposure. These data demonstrated that maternal PCP exposure resulted in prolonged exposure of the developing CNS and also indicated that gestational exposure to PCP decreased high affinity binding sites of PCP in term fetal brain. PMID- 2576303 TI - Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain. AB - THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the [35S]TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of [35S]TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects. Results from these experiments suggest that chronic exposure to THC does not produce significant alterations in catecholamine or indoleamine neurotransmitter systems or in opiate or GABA receptor systems in the rat brain. PMID- 2576304 TI - Behavioral and neurochemical effects of orally administered MDMA in the rodent and nonhuman primate. AB - MDMA (methylenedioxymethamphetamine) is a recreational drug of abuse known as "Ecstasy" which markedly decreases regional brain serotonin (5-HT) content and produces 5-HT nerve terminal degeneration in forebrain areas of the rat. In order to determine the acute and chronic behavioral effects of MDMA, adult rats were given MDMA at 0, 5 or 10 mg/kg, po for 4 consecutive days. Alternatively, parachloroamphetamine (PCA) at 5 mg/kg was administered under the same regimen. Within 30 min after the first dose, the MDMA-treated rats exhibited the serotonin motor syndrome consisting of straub tail and splayed hindlimbs comparable to that seen in the PCA-treated rats. This serotonin motor syndrome, with a duration of about 2 hr, was less pronounced after subsequent doses. At 2-4 wk after the last dose, no significant differences between control and treated rats were seen in emergence, hot plate response, auditory startle response or complex maze behavior even though a significant dose-related decrease (50%) in 5-HT concentration was observed in the frontal cortex and hippocampus of these rats 4 wks after the last dose. Adult female monkeys dosed po with 5 or 10 mg/kg of MDMA twice/day for 4 consecutive days demonstrated no spontaneous behavioral changes or weight loss compared to controls, but forebrain 5-HT concentration was reduced by 80% 1 mon after dosing. These data indicate that at doses only 2-3 times the human dose, MDMA produces significant forebrain 5-HT decreases but does not produce detectable residual behavioral alterations as assessed by these behavioral paradigms. PMID- 2576305 TI - Benzodiazepine-like behavioral effects following withdrawal from chronic delta-9 tetrahydrocannabinol administration in rats. AB - Chronic exposure to cannabis extract or delta-9-tetrahydrocannabinol (THC) has been reported to produce hippocampal neuropathology in rats, as well as classical "hippocampal" behavioral deficits. In an attempt to replicate and extend these findings, male rats were exposed to THC for 13 consecutive weeks, beginning in early adolescence. Drugs were administered five consecutive days a week (Monday through Friday). There were five dose levels: vehicle control, 5, 10, or 20 mg/kg, p.o., and 20 mg/kg THC four days a week (Monday-Thursday), followed by 60 mg/kg on Friday. Following THC exposure, all animals were withdrawn from drugs for seven weeks prior to behavioral testing. Three behavioral tasks previously shown to be sensitive to hippocampal damage were assessed. These were habituation of open-field activity, 24-hr passive avoidance response retention, and complex maze performance. A fourth task, emergence latency, was also included because it has been determined to be sensitive to "anxiety" levels. To facilitate interpretation of the complex maze data, two additional experiments are also reported. One experiment tested rats exposed to trimethyltin (TMT, a potent hippocampal neurotoxicant) on the complex maze. The second assessed the affects of chronic/acute benzodiazepine (BZ) exposure upon maze performance. Test results did not suggest that chronic THC exposure produced behavioral deficits resembling those seen following hippocampal damage. Habituation rates in an activity monitor were identical for all exposure groups, and there was no passive avoidance retention deficit. Further, while TMT caused pronounced abnormalities in the complex maze, chronic THC exposure at the two highest dose levels significantly improved maze performance, similar to BZ effects on this task. Chronic THC also appeared to reduce freezing on the emergence task, another anxiolytic-like effect. These results support other reports of persistent long-term behavioral effects of chronic THC exposure. However, they suggest that some behavioral effects may more closely resemble the effects of minor tranquilizers rather than hippocampal damage. PMID- 2576306 TI - Role of endogenous excitatory amino acid neurotransmitters in the pathogenesis and evolution of acute brain injury. PMID- 2576307 TI - [Use of lasers in gastroenterology]. PMID- 2576308 TI - The macromolecular organization of human centromeric regions. PMID- 2576309 TI - Molecular characterization of human minichromosomes in Chinese hamster/human somatic cell hybrids. PMID- 2576310 TI - The selective dopamine D1 receptor agonist SK&F 38393: its effects on palatability- and deprivation-induced feeding, and operant responding for food. AB - A series of experiments investigated the involvement of the dopamine D1 receptor subtype in relation to feeding responses. The selective D1 agonists, SK&F 38393 (1.0-20 mg/kg) and SK&F 75760 (5 mg/kg), significantly reduced palatable food consumption in nondeprived rats. The anorectic effect of SK&F 38393 (10 mg/kg) was additive with that of the selective D2 receptor agonist, N-0437 (0.3 mg/kg). In nondeprived mice, SK&F 38393 had a stereoselective effect to reduce palatable food intake. At a peripherally-selective dose (3.0 mg/kg), the peripheral dopamine D1 receptor agonist, fenoldopam, had no effect on food intake. At 10 mg/kg, however, it exhibited anorectic properties, although this may have been due to some penetration of the blood-brain barrier. In rats adapted to a food deprivation schedule, SK&F 38393 (3.0-30 mg/kg) produced significant dose dependent reductions in consumption of powdered chow and in lever-pressing for food pellets on a FR8 schedule of reinforcement. In rats adapted to a water deprivation schedule, SK&F 38393 (3.0-30 mg/kg) was substantially less effective in reducing water intake. The results are discussed in terms of a possible selective effect of D1 agonist activity on feeding behaviour. PMID- 2576311 TI - Levodopa-induced dyskinesias in parkinsonian monkeys: relationship to extent of nigrostriatal damage. AB - The relationship between severity of dopa-induced parkinsonian symptoms and the latency and severity of dopa-induced dyskinesias was studied in monkeys exposed to the toxin MPTP. Levodopa and D-2 receptor agonist-induced dyskinesias appeared early, between 2 and 12 days after initiation of dopa therapy in severely parkinsonian animals. In these animals, it was difficult to find a dose of L-dopa which had beneficial effects clinically and no dyskinesia-producing effects. These animals were all found to have massive (greater than or equal to 95%) striatal dopamine loss. A monkey with mild parkinsonian symptoms never developed dyskinesias similar to those produced in the severely affected animals. Stereotypies could be induced in this animal with excessively high doses of L dopa or the dopamine D-2 receptor agonist, LY-171555. These movements were controlled by reducing the drug dose. This animal had less severe striatal dopamine loss (less than 80%) than the former group of monkeys. These results suggest that dopa dyskinesias in parkinsonian monkeys may be related to the extent of damage sustained by the nigrostriatal system. PMID- 2576312 TI - Effects of dopamine D1 and D2 receptor antagonists on oral activity in rats. AB - Two experiments were performed to investigate the actions of the selective D1 blocker SCH 23390 and the selective D2 blocker sulpiride, on oral movements in rats; these were quantified by a human observer scoring vacuous chewing movements (VCMs), jaw tremor and head movements, as well as a computer analysis system which measured the amplitude and slope of each movement. In the first experiment it was found that both SCH 23390 and sulpiride decreased VCMs and head movements in a dose-dependent manner, with SCH 23390 more effectively decreasing head movements and sulpiride more effectively decreasing VCMs. In a second experiment, the effectiveness of these two drugs in blocking the actions of selective D1 (SKF 38393) and D2 (LY 171555) agonists was studied. The SKF 38393-induced increase in computer-scored movement was attenuated by both sulpiride and SCH 23390, whereas the LY 171555-induced decrease in VCMs was attenuated by sulpiride, while SCH 23390 exacerbated it. These findings, together with our earlier results, suggest a simple relationship of D1 receptors to oral movement, with increased activation resulting in increased oral movement and decreased activation resulting in decreased oral movement. The relationship of D2 receptors to oral movement shows a more complex pattern, with both stimulation and blockade decreasing oral movement. One possibility may be the existence of more than one subpopulation of D2 receptors mediating these effects. PMID- 2576313 TI - Mediation of rat postejaculatory 22 kHz ultrasonic vocalization by dopamine D2 receptors. AB - We investigated the role of dopamine receptor subtypes in the regulation of ultrasonic vocalization and masculine copulatory behavior. Intact sexually experienced male Long-Evans rats were treated with saline, selective dopamine D1 (SKF 38393) and D2 (LY 171555) receptor agonists and with selective dopamine D1 (SCH 23390) and D2 (raclopride) receptor antagonists 15 and 30 min before the 30 min test session, respectively. Mating stimuli were ovariectomized female rats injected SC with estradiol benzoate (8 micrograms/0.1 ml/rat) and progesterone (200 micrograms/0.1 ml/rat), 48 and 4 hr before the test session, respectively. We found a decrease in the number of intromissions required to reach ejaculation in animals treated with SKF 38393 (10 mg/kg/IP), LY 171555 (doses ranging from 0.01 to 0.5 mg/kg/SC) and with raclopride (0.1 mg/kg/SC). LY 171555 reduced the postejaculatory vocalization (PEV) in a dose-dependent fashion with complete suppression at the highest dose. No other parameters of sexual behavior were affected by this treatment. Raclopride, a dopamine D2 receptor antagonist, antagonized the suppressive effects of the D2 agonist LY 171555 on the PEV (and also decreased the number of intromissions to reach ejaculation), whereas SCH 23390, a dopamine D1 receptor antagonist, did not. Raclopride, given alone at the dose of 0.5 mg/kg/SC, almost completely suppressed all behavioral activity, whereas the lower dose (0.1 mg/kg) decreased intromission frequency and increased the length of the 22 kHz PEV. Therefore, we suggest that 22 kHz PEV is under the control of dopamine D2 receptors. PMID- 2576315 TI - Corticotropin-releasing factor: putative neurotransmitter in the noradrenergic nucleus locus ceruleus. AB - The effects of hemodynamic stress produced by i.v. infusion of nitroprusside on discharge characteristics of noradrenergic locus ceruleus (LC) neurons were compared to those produced by central administration of corticotropin-releasing factor (CRF). Like CRF, both nitroprusside infusion and blood volume withdrawal increased LC spontaneous discharge. Additionally, nitroprusside disrupted the response of LC cells to repeated sciatic nerve stimulation in a manner similar to CRF. The neuronal effects of nitroprusside were prevented by prior administration of a CRF antagonist, alpha helical CRF9-41, but not by dexamethasone, which blocks CRF release into the hypophysial portal circulation. These results suggest that LC activation by hemodynamic stress is mediated by neuronal CRF release onto LC neurons. alpha Helical CRF9-41 had no effect on the magnitude or timecourse of nitroprusside-elicited hypotension, suggesting that LC activation by nitroprusside is not important for maintaining hemodynamic homeostasis. Finally, chronic administration of desmethylimipramine (DMI) attenuated the response of LC cells to nitroprusside, but not to CRF, suggesting that antidepressant therapy may inhibit stress-induced CRF release. This study supports the concept that CRF serves as a neurotransmitter in the LC in the initiation of stress responses. PMID- 2576316 TI - Acute treatment response and short term outcome in schizophrenia: first results of the NIMH treatment strategies in schizophrenia study. Treatment Strategies in Schizophrenia Collaborative Study Group. PMID- 2576314 TI - Different roles of alpha-noradrenergic receptor subtypes in regulating lordosis. AB - Ovariectomized guinea pigs were given free estradiol (E) at hr 0 and 28, and progesterone (P) at hr 39. Experiment 1: The alpha-1 noradrenergic antagonist prazosin, but not the alpha-2 noradrenergic antagonist idazoxan, prevented display of lordosis behavior when administered systemically 30 min prior to E injections at either hr 0 or 28, or 30 min prior to both injections. Experiment 2: Multiple injections of idazoxan (i.e., 30 min prior to and 60 and 120 min after each E injection) failed to prevent display of lordosis. Experiment 3: E primed animals were given a single injection of idazoxan 1 hr before P, or 5 hr after P. In those animals given idazoxan 1 hr before P, display of lordosis was not prevented. However, in animals given idazoxan once lordosis display had begun (i.e., 5 hr after P) ongoing lordosis behavior was blocked. These data suggest differential roles of alpha-noradrenergic receptor subtypes in regulation of lordosis: noradrenergic transmission through the alpha-1 subtype may mediate hormone-priming processes leading to lordosis, whereas transmission through the alpha-2 subtype may modulate ongoing lordosis responses. PMID- 2576317 TI - Actions of typical and atypical antipsychotics on tuberoinfundibular dopamine neurons. AB - The activity of tuberoinfundibular dopamine neurons, as judged from the accumulation of dihydroxyphenylalanine (DOPA) after the inhibition of decarboxylase activity, was unaltered following the acute administration of the typical antipsychotics haloperidol, cis-flupentixol, chlorpromazine, or fluphenazine. In contrast, a significant increase in the activity of tuberoinfundibular dopamine neurons was elicited by the purported atypical antipsychotics clozapine, melperone, thioridazine, setoperone, and RMI 81582. The clozapine-induced increase in the activity of tuberoinfundibular dopamine neurons was antagonized by the D1 agonist SKF 38393, but not by the D2 agonist quinpirole. The stimulatory effects of atypical antipsychotics on the activity of these hypothalamic dopamine neurons was mimicked by neurotensin and its analogue [D-Trp11]-neurotensin. Moreover, like typical antipsychotics, neurotensin and its analogue also increased serum concentrations of corticosterone. The production of an acute activation of tuberoinfundibular dopamine neurons, which is sensitive to D1 receptor activation and may be mediated by neurotensin, appears to be an effect that distinguishes typical and atypical antipsychotics. PMID- 2576318 TI - The effects of clozapine and fluperlapine on the in vivo release and metabolism of dopamine in the striatum and in the prefrontal cortex of freely moving rats. AB - The effects of the two atypical neuroleptics clozapine and fluperlapine on the dopaminergic function in the striatum and in the prefrontal cortex were studied using the transversal microdialysis technique in awake, freely moving rats. Although neither drug induced catalepsy in rats, both increased the release of dopamine (DA) and the output of its metabolites in a similar way in both areas. Unlike classical neuroleptics, after clozapine and fluperlapine administration, the stimulation of DA release was strictly coupled to that of the metabolites, and a second injection was able to renew it. Pretreatment with the selective D1 agonists SKF 38393 or CY 208-243, by themselves ineffective on the release of DA, antagonized the effects of low doses and substantially reduced those of higher doses of clozapine and fluperlapine, indicating that these two atypical drugs act, depending on the dose, selectively or partially through D1 receptors. PMID- 2576320 TI - Partial brain dopamine D2 receptor agonists in the treatment of schizophrenia. AB - Partial dopamine agonists showing high affinity but low efficacy at D2 receptors can act as dopaminergic "buffers," reducing dopaminergic activity when it is excessive, and promoting it when reduced. This makes them of interest as potential therapeutic agents for the treatment of both positive and negative symptoms in schizophrenia, where they should also result in fewer or less severe motor disturbances than classical neuroleptics. SDZ 208-911 and SDZ 208-912 are amino-ergolines exhibiting partial agonistic properties in the rat, where they inhibit apomorphine-induced stereotypies, are only weakly cataleptogenic, induce varying degrees of circling behavior after unilateral lesioning of the nigrostriatal pathway, and strongly suppress prolactin secretion. The least agonistically acting agent, SDZ 208-912, should be effective against positive symptoms, whereas SDZ 208-911 could be suitable for the treatment of negative symptoms. In addition to possible therapeutic effects, the clinical testing of this class of agent should help to elucidate the status of central dopaminergic function in schizophrenic psychosis. PMID- 2576319 TI - The ratios of serotonin2 and dopamine2 affinities differentiate atypical and typical antipsychotic drugs. AB - Atypical antipsychotic drugs such as clozapine, fluperlapine, and melperone produce weak catalepsy in rodents, and minimal extrapyramidal symptoms and serum prolactin elevations in humans, compared to typical antipsychotic drugs such as haloperidol. The biological basis for these differences has been attributed to relatively weak blockade at D2 dopamine (DA) receptors, various effects at D1 receptors, or potent serotonin2 (5-HT2) antagonism, although other possibilities exist. To clarify the relative importance of actions at D1, D2, and 5-HT2 receptors for identification of candidate typical and atypical drugs, we determined the negative log of the Ki (pKi) value of 21 typical and 17 atypical antipsychotic drugs for the striatal D1 and D2 and frontal cortex 5-HT2 receptors of rodent brain. Cluster analysis identified that the 5-HT2/D2 ratio was the most successful means of utilizing this data to classify typical and atypical antipsychotic drugs correctly. A 92 percent accuracy was achieved. PMID- 2576321 TI - Akathisia: selective beta-blockers and rating instruments. AB - beta-Blockers, particularly propranolol, have been shown to be an effective treatment for neuroleptic-induced akathisia (NIA). To examine the relative contribution of beta-1 and beta-2 receptor blockade to the therapeutic effect of propranolol, we studied a beta-1 selective agent (low dose metoprolol) and a beta 2 specific blocker (ICI 118,551). Both agents ameliorated NIA. To further evaluate instruments for quantifying NIA we compared (a) two sets of clinical ratings during the metoprolol study and (b) clinical and electromechanical ratings of NIA during the ICI 118,551 study. The changes in clinical ratings of NIA after metoprolol were similar for most patients; however, the changes in electromechanical and clinical ratings after ICI 118,551 were similar in less than half of the patients studied. PMID- 2576322 TI - Smooth pursuit eye movements in schizophrenia: effects of neuroleptic treatment and caffeine. AB - Abnormal smooth pursuit eye movement (SPEM) has been proposed as a trait marker in schizophrenia. We utilized high resolution infra-red oculography to measure SPEM in 11 neuroleptic-treated schizophrenic patients, 10 drug-free schizophrenic patients, and 11 normals. The most characteristic abnormality was a significant increase in saccadic intrusions during SPEM in schizophrenic patients (p less than .001). SPEM gain was reduced in schizophrenic patients (p less than .005). No significant effects of neuroleptic treatment on SPEM were found, including analysis of seven patients in whom paired data was available. We also measured SPEM prior to and after caffeine ingestion (10 mg/kg) in 10 normals. We found reduced saccadic interruptions as a result of caffeine ingestion compared with placebo (p less than .05). As caffeine has been shown to selectively increase dopaminergic neurotransmission in mesocortical neurons, further study utilizing dopamine agonists during SPEM in schizophrenic patients is warranted. PMID- 2576323 TI - Botulinal neurotoxins as tools in studies of synaptic mechanisms. PMID- 2576324 TI - [Dental autograft: a supplementary dimension in dental practice]. AB - This article deals with the possibilities and limitations of autogenous transplantations. In properly selected cases (trauma, missing teeth,...), this procedure might be a valuable alternative treatment. The indications for transplantation, the surgical technique, the recipient site and the choice of the transplant are discussed. The most important parameters which influence the success of a transplantation are: the stage of root formation, the atraumatic removal and insertion of the germ, the final position of the transplant and the post-operative fixation. Clinical examples will illustrate some indications. PMID- 2576325 TI - [Bronchial peptidergic control and concepts of neurogenic inflammation]. PMID- 2576326 TI - [Neuropeptides and respiratory diseases: prospects in the treatment of asthma]. AB - The autonomic nervous system includes, side by side with the sympathetic and parasymathetic systems, a third, non-adrenergic and non-cholinergic system called NANC. The mediators in this system are peptides acting as neurotransmitters, i.e. neuropeptides. The NANC system has two components: bronchodilator and bronchoconstrictor. The bronchial relaxant system, called non-adrenergic inhibitory system, has several neurotransmitters, viz.: vasoactive intestinal peptide (VIP), isoleucine histidine peptide (IHP) and methionine histidine peptide (MPH), all derived from a common precursor: pre-pro VIP. MHP has been described in man and IHP in some animal species. VIP relaxes the bronchial smooth muscle, is vasodilator and exerts cellular effects in phagocytes, lymphocytes and mast cells. VIP receptors are present on cells. The other component, called non cholinergic excitatory system, has tachykinins as neuromediators, including substance P, neurokinins A and B, neuropeptide K and calcitonin gene related peptide (CGRP). Substance P contracts the bronchi, increases mucus secretion, dilates vessels and also exerts cellular effects in lymphocytes and phagocytes. Tachykinins act through receptors 3 types of which are now known: NK 1, NK 2 and NK 3. Other neuropeptides have been isolated, including galanin, neuropeptide Y, bombesin, gastrin releasing peptide, enkephalins and katacalcin. The coexistence, in pre- and post-synaptic positions, of the conventional mediators (noradrenaline, acetylcholine) and neuropeptides leads to the concept of co transmission and makes the notion of nerve impulse transmission more complex. The development of neuropeptide agonists and antagonists opens new therapeutic prospects in the management of asthma. PMID- 2576328 TI - [Beta-2 adrenergic stimulants in the treatment of asthma: myths and realities]. AB - In this review paper the authors describe the reasons, sometimes complex, which have given birth to such myths as the abuse of beta 2-stimulants generating status asthmaticus, or patients developing clinical tachyphylaxis to this type of drug. While there is no solid ground to believe that beta 2-stimulants can be blamed for the overmortality due to asthma, and while the indications of beta 2 stimulants delivered by metered-dose aerosols can be extended to chronic asthma, it is still necessary to apply certain safety rules when these drugs are inhaled in high doses or given parenterally. Some patients must be encouraged to use inhaled beta 2-stimulants prophylactically, sometimes combined with cromolyn or inhaled corticosteroids, but these patients, their relatives and their doctor should be taught to evaluate lung function by means of a peak-flow meter. A lack of response to beta 2-stimulants must be taken as a warning that systemic corticosteroids and in some cases admission to hospital are needed. PMID- 2576327 TI - [Combination of theophylline and beta-adrenergic agonists in the treatment of asthma: efficacy and tolerance. Review of the literature]. AB - Theophylline and beta 2-mimetic agents have long been used concomitantly in the treatment of asthma, but divergent opinions are lingering on concerning the safety and effectiveness of this combination in both chronic and acute asthma. In this article, the effectiveness and safety of the combined treatment are reviewed on the basis of published experimental studies and controlled clinical trials. Altogether, these publications demonstrate that the combination is more effective in chronic asthma than either of the two drugs taken separately, but the results obtained are more discordant in acute asthma. Concerning the cardiovascular system, some experimental and epidemiological data have probably led to overestimate the cardiotoxicity of the combined treatment. In clinical studies the incidence of severe arrhythmia is low and certainly not higher than with a single drug therapy in both chronic and acute asthma. Owing to its safety, the theophylline-beta 2-mimetic combination can be prescribed widely in order to improve the treatment of the different forms of asthma. PMID- 2576329 TI - [Takayasu's disease localized exclusively in the pulmonary artery]. AB - A 35 year-old woman exhibited a stenotic lesion of the right pulmonary artery with a severe inflammatory syndrome. A diagnosis of Takayasu arteritis was made, although no aortographic abnormality was present. Involvement of pulmonary arteries during the course of Takayasu arteritis is frequent, but a localisation of the disease to the pulmonary arterial tree alone is a very rare condition. PMID- 2576330 TI - Drug interactions with non steroidal anti-inflammatory drugs (NSAIDs). AB - Drug interactions occur when the pharmacologic profile of one drug is altered by the administration of another drug. These interactions may be due to changes in absorption, distribution, metabolism or excretion. NSAIDs are associated with drug interactions but only a proportion are clinically relevant. Many are due to displacement of a drug from its plasma protein binding sites by NSAIDs which are tightly protein-bound. They may not occur with all NSAIDs but might be selective: most NSAIDs do not have clinically important interactions with oral hypoglycemic agents whereas phenylbutazone, azaprozone & aspirin prolong their half-life. Similarly phenylbutazone and azaprozone prolong coumadin's half-life. Lithium clearance may be decreased by indomethacin, piroxicam, phenylbutazone and diclofenac. Methotrexate (MTX) may be displaced from its binding protein sites by NSAIDs. This is generally not clinically relevant with low doses of MTX as utilized in rheumatoid arthritis patients with normal renal function. NSAIDs also may reduce renal blood flow, tubular excretion of drugs & renal prostaglandin production and may attenuate the effect of anti-hypertensive drugs. Renal failure & hyperkalemia have been reported in patients receiving triamterene & indomethacin. The clinician should be aware of important drug-drug interactions prior to prescribing NSAIDs. Continued scrutiny of these effects are indicated to increase the safety profile. PMID- 2576331 TI - [What intensity of the incisional pain in the postoperative period?]. PMID- 2576332 TI - [Inhibition of gastric acid secretion by vascularly perfused secretin and somatostatin in isolated rat stomach]. AB - Effects of secretin and somatostatin on acid secretion and its relation to prostaglandin E, I2 release in the totally isolated vascularly perfused rat stomach were studied. The results showed: (1) Secretin and somatostatin both markedly inhibited acid secretion stimulated by pentagastrin. Indomethacin could reverse the inhibitory effects of acid secretion by secretin and somatostatin. (2) Secretin increased PGE and PGI2 metabolite 6-Keto-PGF1 alpha release significantly. Somatostatin only increased PGE release. Indomethacin could block stimulatory affects of secretin on PGE, 6-Keto-PGF1 alpha release and somatostatin on PGE release. These results indicated that: (1) inhibition of acid secretion by secretin was mediated by PGI2 and PGE release; (2) inhibition of acid secretion by somatostatin was mediated only by PGE release. PMID- 2576333 TI - [Effects of histamine H2-receptor antagonists on hemopoietic reconstruction in bone marrow]. AB - The effects of histamine H2-receptor antagonists (cimetidine and ranitidine) on bone marrow hematopoiesis of normal and sublethally irradiated mice were investigated. It was found that non-toxic dosage of cimetidine had no significant effect on CFU-s of the normal mouse, but it inhibited CFU-GM growth with a dosage dependent relationship and the recovery of CFU-s formation from sublethal gamma ray irradiation. These results suggest that histamine may play a role in bone marrow regeneration after sublethal irradiation. Histamine H2-receptor antagonists can inhibit hemopoietic reconstruction in regenerating bone marrow. PMID- 2576334 TI - Effects of non-psychotropic drugs on conditioned behavior of cats. AB - Cats were trained to obtain food pellets under a cycle reward condition in 4-6 weeks. These conditioned-behavior cats were then used for testing a group of non psychotropic drugs, and any modification of the feeding cycle (FC) was considered as a side effect of the drug on conditioned behavior. All drugs were given orally. Of the 16 non-psychotropic drugs studied, only indomethacin caused a loss and irregularity in the FC. Antihistamines, acetylsalicylic acid, phenoxybenzamine and amantadine reduced the number of FC by about 50%. Studies of conditioned behavior in the cat appear to be useful for both the investigation of drug interactions and the detection of side effects of drugs not ordinarily considered to have central nervous system effects. PMID- 2576336 TI - [Comparison of soldering and welding of non-precious-alloys]. PMID- 2576335 TI - [Expert opinion on accidental teeth injuries. Principles and case histories]. AB - There are considered the principles to be noticed in the expert opinion on teeth injuries resulting from accidents. The corresponding table of physical damage is shown and 3 clinical cases are presented. PMID- 2576337 TI - Restriction fragment length polymorphism analysis in healthy Japanese individuals and Japanese families with Gaucher disease. AB - We analysed the restriction fragment length polymorphism (RFLP) of 30 unrelated, healthy Japanese individuals and the members of seven Japanese families with Gaucher disease (5 Type I, 2 Type III) with the cDNA for human glucocerebrosidase, to investigate the frequency of the RFLP among healthy Japanese individuals and to determine the feasibility of the use of this probe DNA for carrier detection and prenatal diagnosis in Japanese families with Gaucher disease. In the Pvu II polymorphism, the common allele reported by Sorge et al was the rare allele for healthy Japanese individuals. The frequency of the common allele (+) in Japanese was 0.75 and the rare allele (-) was 0.25. The RFLP study was informative for carrier detection in the family in which both parents were heterozygous for the Pvu II polymorphism. Even in the family in which only one parent was heterozygous, carrier detection was feasible by combining the clinical history and the RFLP, although prenatal diagnosis was not feasible. The Kpn I polymorphism was not detected. It is necessary for precise carrier detection and prenatal diagnosis to investigate other restriction endonucleases which reveal the RFLP. PMID- 2576338 TI - Relationship between acupuncture-induced immunity and the regulation of central neurotransmitters in the rabbit: VI. The influence of NDR stimulation on acupuncture regulation of immune function in rabbit. AB - T-lymphocyte transformation ability decreased and the function of the B lymphocyte and mononuclear leucocyte/macrophage system increased when the activity of central serotonergic neurons was enhanced by the stimulation of nucleus dorsal raphe (NDR). These changes induced by NDR stimulation were not effected by electroacupuncture (EA) when EA was performed on the background of NDR stimulation. By comparing these results with the previous resultant that immunoreactions were affected by locus coeruleus (LC) stimulation and LC stimulation plus EA, some regularity had been discovered. So, a hypothesis was put forward by us that the catecholaminergic system plays a main role in EA regulation of cellular immunity while the serotonergic system plays such a role in EA regulation of humoral immunity. PMID- 2576339 TI - Informed consent in the practice of acupuncture. AB - Early records reveal a parental, beneficent attitude, but an uncommunicative approach to the patient. The Nuremberg trials of 1946 demonstrated the need for ultimate responsibility of the physician, and for a well-informed, consenting patient in experimental procedures (Nuremberg Code of 1947). A later report, the Belmont Report (1975) emphasized the difference between therapeutic research and research unrelated to improving the patient's state of health. Acupuncture has the status of an experimental modality, and requires the informed consent discussion and signature on the form by the patient for each procedure. PMID- 2576341 TI - Towards the development of a mathematical model for acupuncture meridians. AB - Traditional concepts of classical acupuncture and Chinese medicine come from a culture which is very different from ours, and there has been considerable problems in their accurate presentation. Our approach is to attempt the development of a mathematical language that links these traditional concepts theoretically to models that can be experimentally tested. We first review some of Manaka's findings, confirmed also by our results, having to do with low intensity stimuli. In particular, Manaka applied polarized agents such as Cu(+) and Zn(-) to nonacupuncture points on a meridian and to the so called "mother and child" points on a meridian. In both cases he observed the pressure pain reaction which increased for one orientation of Cu and Zn on the meridian and decreased for the opposite orientation. Note that in the case of "mother and child" points the observed reaction was in agreement with the so called "five phase (five element)" theory. Also, in the case of the "mother and child" points the effect usually lasted considerably longer than in the case of nonacupuncture points on a meridian. Taking into account the connection between Manaka's results and skin electrical measurements by some electrodermal diagnostic instruments such as Motoyama's AMI, we discuss some equivalent electric circuits for a single meridian and relate them to the nervous system response. In particular, an electrical circuit model similar to the synapse membrane with two ionic channels seems to be especially useful when we try to explain Manaka's clinical results and Motoyama's results on the velocity of propagation of electrical impulses along meridians. We also develop a mathematical model in the form of a linear five dimensional dynamical system of the so called "five phase (five element)" laws such as "creative" cycle, "controlling" cycle, etc., in the case of a single meridian. We connect this model with the membrane type model mentioned above by assuming a simple mass action law, for the dependence of the conductances in the ionic channels on the input signals. This combined model is used to describe the development of a "disease" and its treatment according to the "five phase" theory. Here we interpret the "disease" as a blockage in a meridian, while the treatment initiates the unblocking process. PMID- 2576340 TI - Electro-acupuncture in the treatment of enuresis nocturna. AB - In the present survey, 162 subjects with enuresis nocturna were given electro acupuncture therapy. Specially chosen points were inserted once a day throughout a ten day period. After the therapy term, the success rate was evaluated as 98.2%. PMID- 2576342 TI - Acupuncture induced immunoregulatory influence on the clinical state of patients suffering from chronic spastic bronchitis and undergoing long-term treatment with corticosteroids. AB - 36 patients suffering from chronic spastic bronchitis were treated with acupuncture. The patient group consisted of 13 men and 23 women varying in age from 26 to 64 years, with an average age of 42.2 years. The therapy consisted of two or three months of acupuncture treatment in alternation with an equal period (2 or 3 months) of recess during which no treatment was administered. Before acupuncture, patients had taken corticosteroids either orally and/or intramuscularly for a period of 2 to 24 years. For those taking corticosteroids orally the daily dosages ranged from 10 to 40 mg Encorton (Polfa, Poland). The patients took intramuscular injections of 40 to 60 mg Kenalog (Squibb) every three or four weeks. Acupuncture sessions were twice a week. All the patients had 42 acupuncture sessions. Before the treatment all the patients, and 30 healthy volunteers, made leukocytes migration tests [(in vivo, using the Rebuck method (1) as modified by Southam (2)]. It was found that patients suffering from chronic spastic bronchitis have leukocytes migration defect. This defect increases in patients who have taken corticosteroids. We have also found that after 42 acupuncture sessions the amount of leukocytes in the tissue pool comes close to the value found in healthy persons during leukocyte migration, [(tested in vivo, using the Rebuck method as modified by Southam (2)]. PMID- 2576343 TI - The arterial pulse analyzer as a potential replacement for manual pulse palpation in Oriental medicine. AB - Application of the arterial pulse analyzer now makes it possible to automatically diagnose such geriatric disorders as arteriosclerosis by using simple electrocardiograms and radial, carotid and posterior tibial artery pressure pulse wave charts. If the arterial pulse analyzer is adopted for use in Oriental medical clinics, there will no longer be a need for manual pulse palpation. In brief, applying the arterial pulse analyzer to the 8 key pulses of Oriental medicine yields the following results: 1) 'Slow' or 'rapid' pulses can be defined by the S-S interval (almost identical to the R-R interval of the ECG). 2) 'Slippery' or 'hesitant' pulses can be defined by the S-P time and the Dh/Ch% (P time & Incisura) ratio. 3) 'Floating' or 'submerged' pulses can be defined by the Ph/Ch% (pressure pulse wave to height) ratio. 4) 'Scattered' or 'moderate' pulses can be defined by the S-C- time (E time). Thus, by employing the arterial pulse analyzer, subjectivity problems inherent in the manual pulse palpation used by Oriental medicine for over 1500 years can be analyzed objectively. PMID- 2576344 TI - 5th Annual International Symposium on Acupuncture and Electro-therapeutics. October 19-22, 1989, New York City. Abstracts. PMID- 2576346 TI - Hypertensive crisis during coronary vessel surgery. PMID- 2576345 TI - [Pharmacokinetics of dextromoramide in the surgical patient]. AB - The pharmacokinetics of dextromoramide were studied in nine patients undergoing peripheral vascular surgery. All the patients were anaesthetised with thiopentone and vecuronium. After tracheal intubation, anaesthesia was maintained with 0.5 to 1.5 vol % halothane and a 60%-40% vol nitrous oxide-oxygen mixture. Once the patient's status was stable, a 0.8 mg.kg-1 bolus of dextromoramide was given intravenously. Blood samples were obtained 2, 5, 10, 30, 60, 90, 120, 180, 240, 300, 360, and 420 min afterwards by an arterial catheter. Dextromoramide serum concentrations were measured with high performance liquid chromatography after extraction with an original technique. The pharmacokinetic parameters were calculated by computer using TRIOMPHE. In five patients, a bi-exponential equation best fitted the results, whereas a tri-exponential equation was necessary for the other four. Mean elimination half-life was 215.3 +/- 78.4 min, and the apparent final volume of distribution was 0.58 +/- 0.20 l.kg-1. Hepatic extraction was low, as shown by a mean systemic clearance of 2.0 +/- 0.9 ml.kg 1.min-1. Liposolubility of this drug is the highest of all opiates, with a heptane/water partition coefficient of 12.3. These parameters demonstrate that, in the opiate drug group, dextromoramide has a place apart from the others. PMID- 2576347 TI - Treatment of postoperative hypertensive crises in vascular surgery. PMID- 2576348 TI - [Effect of alpha inhibitors on risk cofactors in patients with hypertension]. AB - Treatment of hypertension aims at preventing strokes and coronary events although diuretics and beta-blockers lowered blood pressure effectively and allowed prevention of strokes in large-scale trials, they did not reduce the incidence of myocardial infarction or coronary death. The failure of diuretics and beta blockers to afford cardiac protection may be due in part to the unfavorable effects of these agents on associated risk factors like hyperlipidemia and smoking. Hyperlipidemia is more prevalent in hypertensive patients than in matched normotensive controls, and the combination of hyperlipidemia and smoking is more frequent than can be expected to occur by chance. Diuretics and beta blockers affect lipid metabolism negatively. Unlike these agents, alpha-blockers do not alter serum lipids and might reduce triglyceride and cholesterol levels. Several trials have shown that the outcome of treatment with beta-blockers was less favorable in smokers than in non-smokers in terms of blood pressure control and prevention of coronary events. A possible explanation is provided by acute experiments in which beta-blockade enhanced the systemic and coronary vasocontriction elicited by smoking, while alpha-blockade had the opposite effect. Although there is reason to believe that alpha-blockers may be preferable to diuretics and beta-blockers for the treatment of high risk hypertensive patients who smoke and/or exhibit high levels of serum lipids, there is a need for larger and longer trials to test their ability to reduce cardiovascular risk. PMID- 2576349 TI - Reciprocal correlation between expression of P-glycoprotein and accumulation of rhodamine 123 in human tumors. AB - The aim of this investigation was to determine whether a correlation exists between expression of the multi-drug-resistance associated P-glycoprotein 170 (P gp170) and the accumulation of rhodamine 123 in human tumors. We investigated a panel of inherently resistant cell lines originating from human kidney tumor specimens and chemotherapeutically pretreated leukemias. The expression of P gp170 was evaluated by means of two different immunohistological methods using two monoclonal antibodies against P-gp170. We found a significant reciprocal correlation between expression of P-gp170 and accumulation of rhodamine 123. This supports the view that P-gp170 might function as efflux pump in human tumors, as previously described for experimental models. PMID- 2576350 TI - Sulfasalazine alters the character of dimethylhydrazine-induced colorectal carcinoma in rats. AB - The etiologic variables involved in the increased incidence of colorectal carcinoma in patients with chronic ulcerative colitis have not been defined. Sulfasalazine is the most commonly used medication in the treatment of ulcerative colitis. It is not known whether the pharmacologic treatment of ulcerative colitis alters the incidence of cancer in man, but a drug related to sulfasalazine has been shown to reduce the incidence of colorectal carcinoma in rats. In this study we examined the effect of sulfasalazine on the development of 1,2-dimethylhydrazine-induced (DMH) colorectal carcinogenesis in rats. Daily oral ingestion of sulfasalazine in doses equivalent to human daily doses resulted in serum salicylate levels in those animals that were comparable to human therapeutic serum salicylate levels. Sulfasalazine administration did not significantly effect the incidence of DMH-induced colorectal tumors. However, sulfasalazine treated animals were found to have significantly smaller tumors and to show a trend towards multiple, flat, sessile, frequently microinvasive tumors compared to the fewer, larger, exophytic tumors observed in animals treated only with DMH. These results demonstrate that in the doses given, sulfasalazine treatment alters the character of DMH-induced colorectal tumors without significantly effecting tumor incidence. PMID- 2576351 TI - Analysis of the estrogen receptor gene structure in human breast cancer. AB - We studied the structure of the human estrogen receptor (ER) gene by Southern blot analysis in 34 tumor samples and normal breast tissues or peripheral blood samples from the same patients. No rearrangement or amplification of the ER gene was seen in either ER-positive or ER-negative breast tumors. One patient showed an apparent constitutional deletion of a non-allelic ("invariant") restriction fragment in DNAs from both normal leukocytes and bilateral breast tumors. Of 20 patients constitutionally heterozygous for an ER gene RFLP, only one showed tumor specific loss of heterozygosity. This is consistent with the ER gene change we noted overall. At the c-myb locus on chromosome 6q adjacent to the ER gene, allele loss occurred in 1 out of 15 informative cases. In addition, tumor specific allelic loss at the c-H-ras1 locus on chromosome 11p occurred in 4 of 22 informative cases, and at the D17S28 locus on chromosome 17p in 2 of 7 informative cases. PMID- 2576353 TI - Chemical synthesis of picumast dihydrochloride. AB - The chemical synthesis of the antiallergic substance picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin dihydrochloride) is described. PMID- 2576352 TI - Restriction fragment length variations and chromosome mapping of two mouse metallothionein genes, Mt-1 and Mt-2. AB - Restriction endonuclease fragment length variations (RFLVs) were found through the use of cDNA probes for metallothionein genes 1 (Mt-1) and 2 (Mt-2) in the mouse. RFLVs were detected in restriction patterns generated by BglII and XbaI in the Mt-1 gene and by PvuII in the Mt-2 gene. All laboratory strains carry the Mt 1a and Mt-2a alleles. Among strains of wild origin, some Western European subspecies (Mus mus domesticus and M. m. brevirostris) also carry the Mt-1a and Mt-2a alleles. In contrast, a European subspecies (M. m. musculus) and the great majority of subspecies from East Asian countries (M. m. molossinus, Chinese mice of wild origin, and M. m. yamashinai) carry the Mt-1b and Mt-2b alleles. A domesticus strain from Bulgaria and two castaneus strains from Thailand and Philippines carry the intermediate combination of Mt-1b and Mt-2a alleles. Using the RFLVs, we mapped the Mt-1 and Mt-2 genes on chromosome 8, and they appear to be very closely linked since no recombination was observed between them in any of the mice examined. Data from three-point cross tests showed that the recombination frequencies are 4.31% between Os and Mt, 15.52% between Mt and Prt 2, and 19.83% between Os and Prt-2. The gene order of Os-Mt-1,Mt-2-Prt-2 has been confirmed. PMID- 2576354 TI - Antiallergic activity of picumast dihydrochloride in several animal species. AB - Picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1 yl]propoxycoumarin dihydrochloride) was compared with cromoglycate, ketotifen and mepyramine as an inhibitor of allergic and anaphylactoid reactions. 1. In guinea pigs, pretreatment with picumast dihydrochloride given intravenously, orally or by inhalation prevented bronchospasm induced by antigen or histamine. The fraction of the bronchospasm remaining after mepyramine pretreatment was further reduced by picumast dihydrochloride. 2. Systemic administration of picumast dihydrochloride inhibited antigen-induced conjunctivitis, whereas mepyramine and ketotifen were inactive. 3. Intravenous and oral pretreatment with picumast dihydrochloride inhibited the antigen-induced mast cell degranulation in rat mesentery. The effective doses of cromoglycate given intravenously were twice as high as those of picumast dihydrochloride. Picumast dihydrochloride did not inhibit antigen-induced bronchoconstriction in rats. 4. The cutaneous reaction induced with Ascaris antigen in atopic monkeys was insensitive to the antihistaminic action of ketotifen, whereas it was inhibited by low doses of picumast dihydrochloride. Both compounds suppressed skin reactions induced by histamine. 5. Picumast dihydrochloride decreased IgE production in atopic high responder mice. It did not prevent autoimmune nephritis in NZB/W mice. 6. In rats, picumast dihydrochloride did not reduce cotton pellet granuloma, nor adjuvant arthritis. The inhibition of carrageenin oedema is presumably due to its anti-oedematous properties rather than to an antiproliferative activity. In conclusion, the inhibition of allergic and anaphylactoid reactions by picumast dihydrochloride can be attributed to a combined inhibition of liberation and action of histamine and other mediators. PMID- 2576355 TI - Metabolism of picumast after administration of picumast dihydrochloride and antiallergic activity of the main metabolites. AB - The present experiments were carried out to elucidate the chemical structure and the pharmacological activity of the main metabolites of picumast (3,4-dimethyl-7 [4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin ). The metabolic pathways were identical in animals and man, but there were major quantitative differences. The fraction of the radioactivity in the plasma attributable to the parent compound 0.5 to 3 h after oral administration of picumast dihydrochloride was less than 15% in animals but 95% to 57% in man. Inhibition of the C3-zymosan-induced chemilumiescence of human leucocytes was taken as an indicator of the diminished liberation of mediators and inhibition of the histamine-induced contraction of isolated guinea-pig lung strips as an example for the antagonism of picumast dihydrochloride to mediators of allergic reactions. Stepwise oxidation of the 3 methyl substituent of the coumarin ring to the alcohol and the carbonic acid increased the histaminolytic potency, but decreased the inhibition of chemiluminescence. Another metabolite formed by cleavage of the piperazine containing side chain was inactive in both tests. PMID- 2576356 TI - Pharmacokinetics of picumast after administration of 14C-picumast dihydrochloride in dogs, rats, rabbits and monkeys. AB - In dogs, rats, monkeys and rabbits, picumast (3,4-dimethyl-7-[4-(4 chlorobenzyl)piperazine-1-yl]propoxycoumarin ) is eliminated from the plasma by metabolic clearance. Its main metabolic pathway is oxidation of the 3-methyl group of the coumarin ring. After oral administration, the parent compound accounted for less than 15% of the concentration of radioactivity in the plasma. In rats the hydroxylation product M2 was the main metabolite in the plasma; in the other species it was the carbonic acid M1. The hydroxylation of picumast was highly saturable, whereas further oxidation was independent of the dose in dogs and only slightly dose-dependent in rats. Picumast, M1 and M2 are pharmacologically active and potentially toxic. The sum of all three was defined as active compounds. The renal clearance of the active compounds, particularly of picumast, was very low. The terminal half-lives of the active compounds varied between 11 h in rats and 26 h in monkeys. The low plasma concentrations of other metabolites are at least partly due to their renal clearance. In dogs the bioavailability of the parent compound was 14%, the absorption of radioactivity 68%. Of radioactivity injected intravenously 54.8% was recovered from the faeces, 21.8% from the urine. The minimum toxic plasma concentrations of the active compounds were calculated from the minimum toxic dose (MTD) found in chronic or reproduction toxicity studies and the ratio Cl/f of total body clearance/bioavailability determined in the present investigations. The results showed that the differences between the MTDs in dogs and rats and on administration in rats by gavage or in the diet are largely due to differences in total body clearance and bioavailability. PMID- 2576357 TI - Effect of picumast dihydrochloride on antigen-induced early and late airway responses in allergic sheep. AB - In this study the effects of picumast dihydrochloride (3,4-dimethyl-7-[4-(4 chlorobenzyl)piperazine-1-yl]propoxycoumarine++ + dihydrochloride) a novel antiallergic agent, on antigen-induced early and late responses in allergic sheep were examined. For all studies picumast dihydrochloride was administered as an aerosol approximately 20 min before airway challenge with Ascaris suum antigen. Allergic sheep were challenged on four occasions each greater than or equal to 14 days apart: one placebo trial and after 1 mg, 2.5 mg, and 5 mg picumast dihydrochloride aerosol (total dose nebulized). Specific lung resistance (SRL) was used as an index of the airway response to antigen and was measured before and serially after antigen challenge. In the placebo trial (n = 11) antigen challenge resulted in significant early and late airway responses (i.e. 382% and 185% increases in SRL, respectively). Picumast dihydrochloride at 1.0 mg (n = 7) did not protect against the antigen-induced increases in SRL. At 2.5 mg (n = 7), picumast dihydrochloride gave 48% and 55% (both p less than 0.05) protection against the early and late airway responses, respectively. These effects were slightly enhanced with 5 mg picumast dihydrochloride (n = 7) giving 63% protection against the early response and 81% against the late response. These results suggest that the antiallergic agent picumast dihydrochloride may provide some benefit in the treatment of allergic airway disease. PMID- 2576358 TI - Pharmacokinetics of picumast dihydrochloride and its active metabolites M1 and M2 in humans. AB - The pharmacokinetics of picumast dihydrochloride (3,4-dimethyl-7-[4-(4 chlorobenzyl)piperazine-1-yl]propoxycoumarin dihydrochloride) and the pharmacodynamically active metabolites M1 and M2 as well as the absolute bioavailability of picumast dihydrochloride have been studied in healthy volunteers after oral administration of the drug in doses which were considerably higher than therapeutically used. After intravenous administration of 10 mg picumast dihydrochloride a peak concentration of 182 ng/ml was achieved at the end of the 1 h infusion. Picumast dihydrochloride was extensively distributed to the tissues (Vz = 130 l) and almost exclusively eliminated by hepatic metabolism (total clearance 95 ml/min, amount of unchanged compound excreted in urine below detection limit). Median elimination half-life was 16.5 h. The absolute bioavailability reached 57%. The relative bioavailability of picumast dihydrochloride was 20% higher after a meal. After a 20 mg oral dose maximum concentrations between 129 and 284 ng/ml were achieved within 1.3 h. The elimination half-life ranged from 10-26 h. No difference existed between oral (14.5 h) and intravenous administration. The metabolites M1 and M2 in human plasma peaked at 3.4 and 4 h. With 41 h (M1) and 34 h (M2) they exhibited longer half-lives than the parent compound. So under steady state conditions the average plasma concentration of these metabolites amounted to about 68% and 40%, resp., of the unchanged drug as calculated by the ratio of the total areas. The total amount of metabolites M1 and M2 recovered in urine was 6.88% of the oral dose administered, i.e. 6.8% M1 and 0.08% M2. The renal clearance was determined as 28 and 0.5 ml/min for M1 and M2, resp. PMID- 2576360 TI - Pharmacokinetics of picumast dihydrochloride in patients with liver cirrhosis. AB - In a randomized parallel group design the pharmacokinetics of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1 yl]propoxycoumarine++ + dihydrochloride) and its active metabolites M1 and M2 were studied after intravenous or oral administration of a single dose of 10 mg picumast dihydrochloride in two groups of 8 patients with liver cirrhosis. After intravenous administration, the terminal half-life of 65 h was about 4 times longer than in healthy subjects although the total body clearance of 87 ml/min was only 7.4% lower. The 3.6-fold increase in the steady-state volume of distribution (351 l) may be due to a higher uptake by the liver and other tissues and/or to a slower re-diffusion from these tissues into the circulation. Only negligible amounts of picumast dihydrochloride appeared in the urine. Picumast dihydrochloride is almost exclusively eliminated by hepatic metabolism. After oral administration peak concentrations were reached at 1.4 h; plasma elimination half-life was considerably longer (107 h), however, without being significantly different from i.v. administration. The two patient groups differed with respect to their drug metabolizing capacity, therefore the absolute biovailability could not be established. The maximum concentration of the metabolites was reached 1.4 to 3.4 h later than Cmax of the parent drug. As compared to healthy subjects the clearance of the metabolites appeared to the reduced to a greater extent than that of the parent compound, so that under steady-state conditions in patients with liver disease these active metabolites will contribute more to the overall therapeutic effect than in normal individuals. 10.4% to 12.8% of the dose were recovered from the urine als M1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576361 TI - Double-blind study on the influence of picumast dihydrochloride on safety-related performance. AB - The antiallergic drug picumast dihydrochloride (3,4-dimethyl-7-[4-(4 chlorobenzyl)piperazin-1-yl]propoxycoumar ine dihydrochloride) was tested in two doses, 2 mg/d and 4 mg/d, in a double-blind group comparison versus placebo using a sample of 48 healthy adult volunteers to determine any effects on safety related performance in the initial phase of treatment and at steady state. Besides seven test procedures covering concentration and reaction performance, visual orientation, eye-hand coordination and vigilance, a survey of subjective well-being was taken using two different methods. Additionally, after reaching steady state, the tests took place and the survey of well-being was carried out in combination with 0.5% blood alcohol concentration. With both doses of picumast dihydrochloride neither statistically significant nor clinically relevant effects were established in the performance or the well-being of the subjects. This also applies in the case of combination with ethyl alcohol. PMID- 2576359 TI - Study of potential kinetic interactions of picumast dihydrochloride and theophylline in vitro and after oral administration in man. AB - The kinetic interaction of picumast dihydrochloride (3,4-dimethyl-7-[4-(4 chlorobenzyl)piperazine-1-yl]propoxycoumarin dihydrochloride) and theophylline has been studied in vitro (displacement from protein binding) and in vivo in healthy male non-smokers after oral administration. In a randomized, three-way cross-over study, 12 subjects received at weekly intervals either separated or combined single doses of picumast dihydrochloride (10 mg) and theophylline (7 mg/kg b.w.) Picumast and its metabolites were analysed in plasma and urine up to 24 h and theophylline was assayed in plasma during the same time. Theophylline pharmacokinetic parameters like time to peak concentration, peak concentration, elimination half-life, area under the plasma concentration-time curve and oral clearance were not changed after a concomitant dose of picumast dihydrochloride. The combination of theophylline and picumast dihydrochloride revealed no significant changes in the picumast pharmacokinetic parameters t1/2, tmax and CLR. However, Cmax and AUC0-24 decreased significantly by 11% and 7%, resp. Additional theophylline administration significantly increased peak concentration of the intermediate active metabolite M2 by 23% from 7 to 8.6 ng/ml. The absorptive parameters, i.e. time to peak and peak concentration of M1 as well as the AUC calculated from 0-24 h and the renal clearance did not differ in single or combined picumast dihydrochloride administration. A supplementary in vitro study showed no change in plasma protein binding of picumast (100 ng/ml) in the presence of theophylline (20 micrograms/ml) and vice versa. In all volunteers picumast dihydrochloride proved to be safe and well tolerated and treatment was not negatively influenced by theophylline co-administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576362 TI - Double-blind controlled crossover study comparing the protective effect of picumast dihydrochloride versus placebo following nasal allergen challenge. AB - The efficacy of picumast dihydrochloride (3,4-dimethyl-7-[4-(4 chlorobenzyl)piperazine-1-yl]propoxycoumarine++ + dihydrochloride) in a dosage of 2 mg o.d. (loading dose = 2 b.i.d. over the first three days) vs. placebo after nasal challenge was investigated in 20 patients with allergic rhinitis in a double-blind, controlled crossover study. The primary objective was the decrease in determinable nasal flow as a result of obstruction caused by swelling of the mucous membrane of the nose following nasal challenge with grass pollen. In addition, picumast dihydrochloride's effect on subjective symptoms elicited by nasal challenge, such as "runny nose" and "irritation", was also assessed. Picumast dihydrochloride's ability to inhibit nasal obstruction after challenge was significantly better than that of placebo in statistical terms. Nasal secretion after challenge with grass pollen was far less pronounced with picumast dihydrochloride than placebo. A positive effect on irritation was not seen after nasal challenge. The results of this study show that picumast dihydrochloride inhibits nasal obstruction and secretion in patients allergic to grass pollens following allergen challenge. It is also expected that picumast dihydrochloride will be able to clearly reduce allergic nasal reactions during times of natural, seasonally-high pollen counts. PMID- 2576363 TI - A placebo-controlled comparison of the efficacy and tolerability of picumast dihydrochloride and terfenadine in patients with seasonal allergic rhinitis. AB - Of 99 evaluable patients with seasonal allergic rhinitis, 33, 35, and 31 were treated with picumast dihydrochloride (3,4-dimethyl-7-[4-(4 chlorbenzyl)piperazine-1-yl]propoxycoumar in dihydrochloride) 1 mg, terfenadine 60 mg, and placebo, respectively, twice daily for 3 weeks. After 7 days' treatment physicians' assessments of symptomatic improvement showed that the effects of the two active drugs were similar and significantly superior to those of placebo. Some further improvement occurred over the remainder of the study, with no significant differences in efficacy appearing between picumast dihydrochloride and terfenadine. After 2 and 3 weeks of treatment the efficacies of both picumast dihydrochloride and terfenadine were "very good/good" in over 90% of patients. The tolerability of all three treatments was classified as "very good" in 60% to 70% of patients. Physicians were prepared to represcribe the study medication in about 90% of patients given picumast dihydrochloride or terfenadine compared with 52% administered placebo. Similar assessments performed by the patients generally agreed with these results. Withdrawal due to lack of efficacy occurred in 13, 2 and 0 patients treated, respectively, with placebo, terfenadine, or picumast dihydrochloride. Few adverse effects were reported. It is concluded that picumast dihydrochloride offers a comparable alternative to terfenadine in the treatment of seasonal allergic rhinitis. PMID- 2576364 TI - Double-blind multicenter controlled clinical study comparing the efficacy of picumast dihydrochloride versus astemizole and placebo in patients with seasonal allergic rhinitis. AB - The efficacy of picumast dihydrochloride (3,4-dimethyl-7-[ 4-(4 chlorobenzyl)piperazine-1-yl]propoxycoumarine dihydrochloride) in a dosage of 2 mg o.d. vs. astemizole (10 mg o.d.) and placebo was investigated in a double blind, controlled multicenter study. During the first 3 days of treatment, the patients were administered double their assigned dose as loading dose. A total of 119 patients were enrolled in the study, of whom 103 were evaluable for efficacy (picumast dihydrochloride n = 35, astemizole n = 35 and placebo n = 33). The primary objective was the number of patients for whom the investigator scored the effectiveness of study medication as adequate or better over a treatment period lasting at least 4 days. A statistically significantly improved efficacy over placebo was demonstrated by picumast dihydrochloride in terms of the primary objective as was a trend to improved efficacy over astemizole. Observation of the length of participation of the patients in the study up to the point of premature stopping due to inadequate efficacy, adverse events or non-compliance demonstrated that clearly more patients in both active drug groups remained in the study over the planned duration of 28 days compared with patients in the placebo group. In this respect, more patients on astemizole dropped out of the study prematurely compared with patients on picumast dihydrochloride. Serious adverse events did not occur.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576365 TI - Efficacy and tolerability of picumast dihydrochloride in comparison with placebo in asthmatic patients. AB - In a randomized double-blind study, 107 patients with extrinisic, intrinsic or mixed bronchial asthma and impaired lung function received either picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1 yl]propoxycoumarin dihydrochloride) 1 mg or placebo twice daily for 6 weeks after a 2-week placebo phase. Patients given picumast dihydrochloride demonstrated significant improvements compared with baseline in morning and evening peak flow and asthmatic symptoms like morning tightness, cough, dyspnoea, obstruction, number of asthma attacks during night and day, sum of asthmatic symptom scores, in vital capacity and Tiffeneau index, and a significant reduction of inhaled adjuvant medications. In contrast, placebo recipients improved significantly only in daytime asthma attacks, obstruction, sum of symptom scores, and Tiffeneau index. The differences between the picumast dihydrochloride and placebo groups significantly favoured picumast dihydrochloride for improvements in mean number of daytime asthma attacks, morning tightness, aerosol use and sum of symptom scores. Adverse reactions were minor and infrequent; no tiredness occurred with picumast dihydrochloride. Tolerability of both picumast dihydrochloride and placebo was rated as "good" to "very good" by patients and physicians. PMID- 2576366 TI - A one-year double-blind clinical study of the efficacy and tolerability of picumast dihydrochloride versus ketotifen in patients with bronchial asthma. AB - The efficacy and tolerability of picumast dihydrochloride (3,4-dimethyl-7-[4-(4 chlorobenzyl)piperazine-1-yl]propoxycoumarin dihydrochloride) (2 mg twice daily orally) in comparison with ketotifen (1 mg twice daily orally) was investigated in 400 patients with bronchial asthma (picumast dihydrochloride n = 202, ketotifen n = 198) in a double-blind, controlled, parallel group study. Assessment of therapeutic and preventative efficacy was by means of symptom scores, quantitative measurements (accumulatory threshold dose) of the bronchial hyperreactivity by means of inhalatory acetylcholine provocation, measurements of peak expiratory flow, vital capacity (VC) and 1-s capacity (FEV1) as well as global assessment of efficacy by the doctor and patient. Tolerability was assessed by recording side effects and global assessment of tolerance on a rank scale at the end of the treatment as well as by means of clinico-chemical parameters. Picumast dihydrochloride and to a lesser extent ketotifen both led to a clinically relevant and statistically significant increase in the inhalatory provocation dose (PD50) for acetylcholine. There was a moderate improvement in the symptom scores and a rise in peak flow values in both treatment groups. The mean total score of asthmatic symptoms of both drugs showed a clear but quantitatively low improvement after 12 months' treatment. The differences in efficacy between picumast dihydrochloride and ketotifen were not statistically significant. During the course of the study, adverse reactions were recorded on 117 occasions (picumast dihydrochloride n = 41, ketotifen n = 76).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576367 TI - Acceptability, safety and efficacy of picumast dihydrochloride on long-term use in patients with perennial bronchial asthma. AB - 104 adult patients with predominantly extrinsic perennial asthma who were maintained on bronchodilator or glucocorticoid therapy, were entered into a one year open study designed to evaluate the efficacy, safety and acceptability of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1 yl]propoxycoumarin dihydrochloride) (2 mg twice daily). 74 patients completed the 12-month treatment period and a further 18 (total 92) were followed up for at least 2 months. Adverse drug reactions were reported in 14 patients and 5 of them were withdrawn from the trial for only non serious reactions. 12 patients were excluded from the analysis of efficacy because they dropped out early and no sufficient data were available for a judgement. Although this was an open study, analysis of diary card measurements and clinical assessments indicate that picumast dihydrochloride could represent a new and effective prophylactic therapy in the long-term management of bronchial asthma. Picumast dihydrochloride improved forced expiratory volume in 1 s (FEV1), peak flow and subjective asthmatic symptoms in 51%, 64% and 70% of the patients, respectively. 92% of those who participated in this study were willing to take the study drug again. PMID- 2576368 TI - Buthionine sulfoximine inhibition of glutathione biosynthesis enhances hepatic lipid peroxidation in rats during acute ethanol intoxication. AB - A single intraperitoneal injection of DL-buthionine-S,R-sulfoximine (BSO) (4 mmol/kg) to overnight-starved rats caused a 70% inhibition of hepatic gamma glutamylcysteine synthetase and induced a decrease in liver-reduced glutathione (GSH) for several hours. There was, however, no difference in hepatic lipid peroxidation, as assessed by malondialdehyde accumulation, between the control and BSO groups. During acute ethanol intoxication (5 g/kg), hepatic lipid peroxidation was increased by approx. 40% within 6 hr. Hepatic [GSH] was also significantly decreased by ethanol. The effect of ethanol on GSH level was not observed in rats pretreated with BSO, though the ethanol-induced enhancement of hepatic lipid peroxidation was potentiated by the BSO pretreatment. Under these conditions there were no apparent effects on blood concentrations of ethanol and acetaldehyde nor on activities of hepatic alcohol dehydrogenase, aldehyde dehydrogenase, glutathione-dependent detoxifying enzymes, superoxide dismutase or catalase. These results suggest that, although a decrease (by BSO) in GSH by itself does not alter the degree of endogenous lipid peroxidation, it is associated with a potentiation of the enhancement of hepatic lipid peroxidation caused by acute ethanol intoxication. PMID- 2576369 TI - [European Conference on Nursing, 21-24 June 1988]. AB - This paper is a description of the European Conference on Nursing held in Vienna, Austria from 21 to 24 June in 1988. The most important papers, statements and speeches presented, are outlined. The "Market Place" and the discussions in the works groups are described. The students views for the conference are also present. PMID- 2576370 TI - [Prokinetic drugs in gastrointestinal motility. Their application in pediatrics]. AB - In this article, the neurophysiology and neurobiochemistry of the digestive system are reviewed briefly. The pharmacology of the main gastrointestinal prokinetic drugs and their indications, side effects and dosages in pediatric patients are described. PMID- 2576371 TI - Retinoids, homeobox genes, and limb morphogenesis. PMID- 2576372 TI - Synthesis of a homodimer neurohormone precursor of locust adipokinetic hormone studied by in vitro translation and cDNA cloning. AB - The homodimer neurohormone precursor P1, consisting of 41 residue subunits or A chains, is synthesized by the glandular neurosecretory cells of the corpora cardiaca (CC) of the locust Schistocerca gregaria. Processing of P1 generates two copies of a 10 amino acid peptide neurohormone (AKH I) and one copy of a homodimer peptide (APRP 1). Here we show that the P1 dimer is formed from two independent A-chain translation products. Translation of CC mRNA in vitro produces a prominent 6.4 kd protein, the synthesis of which can be blocked by oligonucleotides hybridizing to mRNA encoding the A-chain. Northern blot experiments suggest that the 6.4 kd protein is produced by an integral of 500 base mRNA. cDNA cloning reveals a pre-A-chain structure in which a single copy of the A-chain is preceded by a 22 amino acid signal peptide. This evidence indicates that the P1 dimer is synthesized by coupling of very small translational products rather than by folding and processing of a larger protein containing more than one copy of the A-chain. PMID- 2576373 TI - Human gene for torsion dystonia located on chromosome 9q32-q34. AB - Torsion dystonia is a movement disorder of unknown etiology characterized by loss of control of voluntary movements appearing as sustained muscle contractions and/or abnormal postures. Dystonic movements can be caused by lesions in the basal ganglia, drugs, or gene defects. Several hereditary forms have been described, most of which have autosomal dominant transmission with variable expressivity. In the Ashkenazi Jewish population the defective gene frequency is about 1/10,000. Here, linkage analysis using polymorphic DNA and protein markers has been used to locate a gene responsible for susceptibility to dystonia in a large, non-Jewish kinship. Affected members of this family have a clinical syndrome similar to that found in the Jewish population. This dystonia gene (ITD1) shows tight linkage with the gene encoding gelsolin, an actin binding protein, and appears by multipoint linkage analysis to lie in the q32-q34 region of chromosome 9 between ABO and D9S26, a region that also contains the locus for dopamine-beta-hydroxylase. PMID- 2576374 TI - Traumatic neuronal injury in vitro is attenuated by NMDA antagonists. AB - Pure traumatic neuronal injury was modeled in dispersed neocortical cell cultures derived from fetal mice. A plastic stylet was used to tear the neuronal and glial cell layer; medium oxygen content, pH, and glucose remained unchanged. Adjacent to this local disruption, many neurons developed acute swelling and went on to degenerate over the next day, but glia were relatively spared. If the same mechanical insult was delivered in the presence of the N-methyl-D-aspartate (NMDA) antagonists dextrorphan or D-2-amino-5-phosphonovalerate, resultant neuronal degeneration was markedly reduced. The protective effect of these NMDA antagonists was concentration-dependent between 1 and 100 microM, with EC50 near 10 microM for both compounds. Present findings suggest that endogenous excitatory amino acids may participate significantly in the propagation of central neuronal cell loss in response to a purely mechanical insult. PMID- 2576375 TI - Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. AB - Glutamate binds to both excitatory neurotransmitter binding sites and a Cl(-) dependent, quisqualate- and cystine-inhibited transport site on brain neurons. The neuroblastoma-primary retina hybrid cells (N18-RE-105) are susceptible to glutamate-induced cytotoxicity. The Cl(-)-dependent transport site to which glutamate and quisqualate (but not kainate or NMDA) bind has a higher affinity for cystine than for glutamate. Lowering cystine concentrations in the cell culture medium results in cytotoxicity similar to that induced by glutamate addition in its morphology, kinetics, and Ca2+ dependence. Glutamate-induced cytotoxicity is directly proportional to its ability to inhibit cystine uptake. Exposure to glutamate (or lowered cystine) causes a decrease in glutathione levels and an accumulation of intracellular peroxides. Like N18-RE-105 cells, primary rat hippocampal neurons (but not glia) in culture degenerate in medium with lowered cystine concentration. Thus, glutamate-induced cytotoxicity in N18 RE-105 cells is due to inhibition of cystine uptake, resulting in lowered glutathione levels leading to oxidative stress and cell death. PMID- 2576376 TI - Lineage, migration, and morphogenesis of longitudinal glia in the Drosophila CNS as revealed by a molecular lineage marker. AB - Previous studies described three different classes of glial cells in the developing CNS of the early Drosophila embryo that prefigure and ensheath the major CNS axon tracts. Among these are 6 longitudinal glial cells on each side of each segment that overlie the longitudinal axon tracts. Here we use transformant lines carrying a P element containing a 130 bp sequence from the fushi tarazu gene in front of the lacZ reporter gene to direct beta-galactosidase expression in the longitudinal glia. Using this molecular lineage marker, we show that 1 of the "neuroblasts" in each hemisegment is actually a glioblast, which divides once symmetrically, in contrast to the typical asymmetric neuroblast divisions, producing 2 glial cells, which migrate medially and divide to generate the 6 longitudinal glial cells. As with neuroblasts, mutations in Notch and other neurogenic genes lead to supernumerary glioblasts. The results indicate that the glioblast is similar to other neuroblasts; however, the positionally specified fate of this blast cell is to generate a specific lineage of glia rather than a specific family of neurons. PMID- 2576377 TI - A comparison of vecuronium by continuous infusion with either isoflurane or fentanyl-nitrous oxide anesthesia. AB - The average infusion rate and efficacy of vecuronium bromide continuous infusions for surgical relaxation in human subjects was evaluated. Nineteen adult patients requiring more than 120 min of neuromuscular blockade for surgery were randomized to receive either fentanyl-nitrous oxide (Group 1) or isoflurane-fentanyl-nitrous oxide (Group 2). Neuromuscular function was monitored using train-of-four evoked electromyography (EMG). Following an intubating dose of 0.08 mg/kg of vecuronium bromide, the first twitch was allowed to return to 10% of its control value. An infusion of vecuronium at an initial rate of 60.0 micrograms/kg/h was then started and adjusted to maintain the first twitch at 10% of control. The average infusion rate (total infusion dose divided by the duration of the infusion) was 57.2 +/- 14 micrograms/kg/h in Group 1 (n = 10) and 42.4 +/- 12 micrograms/kg/h (n = 9) in Group 2, approximately 25% less (p = 0.02). There was a significant decrease in the infusion rate with time in Group 1 (p = 0.02), but this decrease was not observed in Group 2. PMID- 2576379 TI - Pharmacologic modulation by cetirizine-2 HCl of cutaneous reactions and pruritus in man after experimental mosquito bites. PMID- 2576378 TI - Serum potassium concentrations following succinylcholine in patients undergoing beta-adrenoceptor blocking therapy. AB - Efflux of serum potassium following succinylcholine was compared in surgical patients undergoing low-dose, long-term beta 1-adrenoceptor or beta 1,2 adrenoceptor blocking therapy and in those receiving neither of these therapies. There were no significant differences in serum potassium concentration prior to, and over a study period of, 2 hours following succinylcholine administration among the three groups of patients. PMID- 2576380 TI - Transcription factors. PMID- 2576381 TI - Sorting signals. PMID- 2576382 TI - Synaptic vesicles. PMID- 2576383 TI - Clathrin-coated vesicles. PMID- 2576384 TI - Ion-coupled neurotransmitter transport. PMID- 2576386 TI - Knowledge-based design of artificial worlds. AB - We review the concepts of knowledge representation and modelling and simulation methodology which facilitate computer exploration of alternative artificial worlds, such as self-sufficient human habitats. An object-oriented computer environment which supports such simulation studies is briefly described. A simplified example of an artificial world model is given to demonstrate the power of the approach. PMID- 2576385 TI - [Subdural empyema successfully treated with medical therapy]. PMID- 2576387 TI - Elimination of T cells from human bone marrow and peripheral blood by means of E rosettes and density gradient centrifugation. PMID- 2576388 TI - New strategies in the treatment of immunological and other inherited diseases: allogeneic stem cells transplantation. PMID- 2576389 TI - Autologous bone marrow or peripheral blood stem cell transplantation for patients with chronic myelogenous leukaemia in chronic phase. AB - The progressive and fatal course of chronic myelogenous leukemia has not been affected significantly by chemotherapeutic agents that control the benign phase of the disease. Combination chemotherapy and aggressive treatments may offer some advantages: however, these approaches do not appear to produce stable suppression of Ph1 chromosome or to prolong chronic phase and survival of these patients. Only allogeneic bone marrow transplantation has been demonstrated to be capable of inducing a stable, complete suppression of Ph1+ cells. Recently alpha Interferons (IFN) have been shown to control myeloid proliferation in patients with CML and to determine a progressive and persistent decline of Ph1+ bone marrow cells in some cases. The hypothesis that in most newly diagnosed patients with CML various amount of Ph1 negative cells must still be present, albeit in suppressed state in the bone marrow (BM) or in the peripheral blood (PB), have led some Authors to treat patients with high-dose chemotherapy followed by reinfusion of stem cells collected at diagnosis or after a response to cytoreductive treatments. We report 34 patients with CML treated in chronic phase with Busulohan and Melphalan conditioning regimen followed by reinfusion of BM or PB stem cells. PMID- 2576390 TI - [Spinal neurotransmitters: chemical neuroanatomy of the human spinal cord and the cultured sensory neurons of the adult rat]. AB - The purpose of this paper is to illustrate the advantages of immunocytochemical studies of spinal neurotransmitters in human pathology and in animal experiments the distribution of transmitters, mainly of neuropeptides in the human spinal cord is summarized. Data obtained on pathological material are able to determine the origin of certain peptidergic afferents to the spinal cord and suggest that the early selective disappearance of substance P-fibers plays a role in the pathogenesis of amyotrophic lateral sclerosis. Transmitter immunocytochemistry is useful for assessing the plasticity of spinal neurons in chemically induced degeneration of the gray matter and in a model of spinal cord trauma. Finally, a newly developed culture system of adult rat and human dorsal root ganglia demonstrates that the phenotypic expression of neurotransmitters can be modulated experimentally, which offers new perspectives for studying their neurobiological role and for the tentative repair of central nervous system lesions by autografts. PMID- 2576391 TI - Inter-observer variation in assessment of undescended testis. Analysis of kappa statistics as a coefficient of reliability. AB - In a prospective study the inter-observer variation in the diagnosis of undescended testis was analysed. Two physicians assessed independently the position and motility of the testes of 37 boys referred for undescended testis. The boys were examined in the supine and squatting positions. The observed agreement rate between the observers was 0.90 to 0.97. Using kappa (kappa) statistics, the values were adjusted for the expected chance agreement; kappa values between 0.47 and 0.81 were obtained, slightly higher values for patients in the supine position. Complete agreement on all observations was reached in 13.5% of the patients. Inter-observer variation may be a substantial source of bias in diagnosing the undescended testis and one of the reasons for the varying results in studies of hormonal treatment of this condition. It is also a fact that the number of orchiopexies in some countries exceeds the incidence of this condition. PMID- 2576392 TI - [The effect of ethanol on gamma-aminobutyric acid in the brain]. AB - The effect of acute and chronic ethanol administration on the level of gamma aminobutyric acid (GABA), glutamate, aspartate, and glutamine was investigated. The level of GABA rose both after acute and chronic ethanol administration. In chronic experiments also the level of glutamate, aspartate and glutamine were increased. In acute experiments the incorporation from glucose into the studied amino acids (neuronal compartment) increased, while in chronic experiments a decreasing trend was observed. In the glial compartment the incorporation increased only into glutamate and glutamine in acute experiments, while in chronic experiments a decreased incorporation into glutamine was recorded. The activities of three enzymes were studied in seven parts of the brain after acute ethanol administration. The activity of glutamic acid decarboxylase increased in the hypothalamus and brain cortex and decreased in the medulla oblongata. The activity of GABA transaminase did not change and the activity of glutamine synthetase decreased only in the hippocampus. In accordance with several other studies, the presented results show that ethanol interferes with the GABA system in the brain. It is suggested that the primary effect of ethanol is exerted on the cell membranes with preference for the regions connected with the GABA system. PMID- 2576393 TI - Incorporation of intraportally infused [15N]ammonia into urinary uric acid in cockerels pretreated with methionine sulfoximine. AB - 1. Measurements were made in situ to determine the incorporation of intraportally infused ammonia-15N into urinary uric acid in cockerels pre-treated with methionine sulfoximine (MSM), a glutamine synthetase inhibitor. 2. The incorporation of 15N into urinary uric acid was 34% of the infused amount in MSM treated birds. This was not significantly different from the value of 46% for control birds. 3. Pre-treatment with MSM inhibited the activity of liver glutamine synthetase to 7% of the control value and decreased the incorporation of the infused ammonia-15N into plasma glutamine amide-N to 3% of the control. 4. Increases in glutamine concentrations in the blood, liver and kidney caused by the infusion of ammonia were also completely inhibited by the MSM treatment (P less than 0.05). 5. It is concluded that in the cockerel ammonia-N can be incorporated into uric acid other than by glutamine formation. PMID- 2576394 TI - Effect of glucocorticoids on the response of airway smooth muscle to catecholamine and resorcinol beta-agonists. AB - The influence of hydrocortisone (11 beta, 17 alpha, 21-trihydroxy-pregn-4-ene 3,20-dione) or of methylprednisolone (6 alpha-methyl-11 beta, 17 alpha-21 trihydroxy-1,4-pregnadiene-3,20-dione) on the response of airway smooth muscle to a variety of beta-adrenergic bronchodilators was evaluated using incubated guinea pig tracheal rings, preconstricted with histamine. The adrenergic agonists chosen for this study included the nonselective beta 1- and beta 2-catecholamine, isoproterenol, the selective beta 2-catecholamine, rimiterol, and the selective beta 2-resorcinols, fenoterol and terbutaline. When the incubated rings were pretreated with 10-50 micrograms/mL of the steroids, there was a significant enhancement in smooth muscle sensitivity and reactivity to rimiterol and isoproterenol. Tracheal response to fenoterol or terbutaline, on the other hand, was not altered by the glucocorticoids. When used alone, neither steroid exerted an inotropic influence on the tracheal smooth muscle. The results of our study indicate that glucocorticoid enhancement of adrenergic bronchodilators is selective for catecholamines, and not for resorcinols. PMID- 2576395 TI - Adrenergic interactions in uterus and vascular smooth muscle in rats in vivo. AB - Simultaneous blood pressure and uterine responses to norepinephrine infusions were recorded in urethane-anesthetized, pentolinium-indomethacin treated rats in natural estrus under conditions in which no blockers or blockers of alpha 1-, alpha 2-, and beta-adrenergic receptors or of "reuptake" of norepinephrine were present. The contributions of alpha 1- and alpha 2-adrenergic receptors to the blood pressure response were similar during the initial portion of the response. At later times, however, alpha 1-adrenergic receptors were responsible for the major portion of the response. The tachyphylaxis of the pressor response that occurs during norepinephrine infusion could be prevented by preventing norepinephrine "reuptake" with imipramine. In the uterus, the initial small alpha adrenergic contractile response (seen only at the lowest infusion rate) was quickly overwhelmed by a beta-adrenergic relaxing component. Administration of the beta-adrenergic receptor blocker, propranolol, during norepinephrine infusion caused similar increases in blood pressure in control, yohimbine-, and prazosin treated rats. Uterine contractions, in contrast, were only significantly elevated during beta-adrenergic receptor blockade when yohimbine or imipramine had also been administered. PMID- 2576396 TI - Percutaneous transluminal angioplasty in nonspecific aortoarteritis (Takayasu's disease): experience of 16 cases. AB - Sixteen patients with aortoarteritis underwent percutaneous transluminal angioplasty for dilatation of 19 stenotic arteries. Sites included renal arteries (9), subclavian arteries (5), innominate artery (1), abdominal aorta (2), and descending thoracic aorta (2). Angiographic success was obtained in 14 lesions (74%) and partial success in 1 stenosis. The procedure was unsuccessful in 3 renal and 1 subclavian stenoses (21%). There were three complications. Clinically, there was cure of hypertension in three patients and improvement in six patients who had hypertension. Relief of claudication or return of pulsations was observed in seven patients. There was no evidence of any recurrence in the follow-up period (2-33 months). We conclude that percutaneous transluminal angioplasty is a safe and effective procedure for treating symptomatic stenotic lesions in aortoarteritis. PMID- 2576397 TI - Effect of CV 205-502 in hyperprolactinaemic patients intolerant of bromocriptine. AB - CV 205-502 (Sandoz), an octahydrobenzol [g]quinoline, is a long-acting dopamine agonist which inhibits prolactin secretion. We conducted a phase 2 clinical study in 10 hyperprolactinaemic women (nine of whom were previously intolerant of bromocriptine) in order to determine (1) the dose at which CV 205-502 exerted its prolactin-lowering effect; (2) the nature of adverse reactions associated with long-term therapy; and (3) whether patients who were intolerant of bromocriptine could tolerate CV 205-502. At first patients were randomized to take initial doses of either 0.02 or 0.05 mg daily at bedtime. Thereafter these doses of medication were gradually increased either to the point of normalizing serum prolactin (to 0.70 IU/l or 20 ng/ml) or to a maximum dose of 0.14 mg daily. The lower initial dose was ineffective and had to be increased in all patients. The higher initial dose (0.05 mg) normalized prolactin in three of five women within 24 h. During chronic administration of the final dose of CV 205-502 (mean 0.09 mg a day), serum prolactin decreased from a mean level of 9.19 +/- 4.9 (SEM) IU/l to a mean level of 1.55 +/- 0.49 IU/l (n = 10 patients). Prolactin was normalized in five patients. Two patients, one of whom had been previously unresponsive to bromocriptine, and another unresponsive to pergolide with regard to prolactin inhibition, were also unresponsive to CV 205-502. Nausea, the side-effect responsible for these patients' previous intolerance of bromocriptine, occurred in six of 10 patients taking CV 205-502 but was much less disabling and did not cause any of the patients to stop this medication. Only one patient taking CV 205 502 discontinued treatment because of adverse effects (light-headedness). PMID- 2576398 TI - Thyroid autoimmunity in endemic goitre caused by excessive iodine intake. AB - The pathophysiology of endemic goitre caused by excessive iodine intake is not well defined. By interacting with the immune system, iodine excess may trigger the development of autoimmune thyroid disease such as lymphocytic Hashimoto's thyroiditis (LT). In an attempt to examine this further, we compared the presence of thyroid autoantibodies in 29 goitrous children, from an iodine excess area, and in 26 healthy children, from an iodine sufficient area, of north central China. Serum was tested for antimicrosomal (MAb), anti-thyroglobulin (TgAb), second colloid antigen antibodies (CA2-Ab) and TSH binding inhibitory immunoglobulins (TBII). Affinity chromatographically purified IgG was tested for thyroid growth-stimulating activity (TGI) by two different methods: a sensitive cytochemical bioassay (CBA) using guinea-pig thyroid explants and a mitotic arrest assay (MAA) employing a continuous rat thyroid cell line (FRTL-5). We found no increased prevalence of LT in patients with endemic iodine goitre. The levels of MAb, TgAb and CA2-Ab did not differ significantly between the two groups of children. Further, TBII were not present in either group. Thyroid growth-stimulating immunoglobulins (TGI) were the major autoantibodies found in children with goitres caused by iodine excess. In the CBA, 12 of 20 (60%) goitrous children and 0 of 12 (0% P less than 0.05) healthy children were positive for TGI. Similar results were found in the MAA, and a good correlation between results of the CBA and MAA was found (P = 0.003). Maximal TGI activity in dose-response CBA showed a good relation with clinical goitre size (r = 0.63; P less than 0.05) indicating a possible pathophysiological role for these antibodies. We conclude that endemic iodine goitre is not associated with Hashimoto's lymphocytic thyroiditis. Nevertheless, autoimmune growth factors such as TGI may play a primary role in the pathogenesis of thyroid growth in this condition. PMID- 2576399 TI - Bimodal and graded expression of the Xenopus homeobox gene Xhox3 during embryonic development. AB - A Xenopus laevis homeobox gene, Xhox3, has been isolated using the homeobox of the Drosophila pair-rule gene even skipped as a hybridization probe. Xhox3 is first transcribed at the midblastula transition; RNA levels peak at the early neurula stage and decrease thereafter. During the early period of Xhox3 expression, the gastrula and neurula stages, transcripts are found in a graded fashion along the anteroposterior (A-P) axis in the mesoderm and are most concentrated at the posterior pole. In the late period of expression, the tailbud and tadpole stage, transcripts are concentrated at the two ends of the embryo: in the anterior nervous system and posterior tail bud. Analysis of Xhox3 expression in experimentally perturbed embryos shows that different A-P fates in the mesoderm are correlated with different levels of Xhox3 expression. Based on these results and those with other frog homeobox genes, we propose a role for homeobox genes in the patterning of the A-P embryonic axis. PMID- 2576400 TI - Mouse homeo-genes within a subfamily, Hox-1.4, -2.6 and -5.1, display similar anteroposterior domains of expression in the embryo, but show stage- and tissue dependent differences in their regulation. AB - By use of in situ hybridization experiments on mouse embryo sections, we compare the transcript patterns of three homeo-genes from the Hox-1.4 subfamily (Hox-1.4, -2.6 and -5.1). Genes within a subfamily are true homologues, present in the genome as a result of duplication of an ancestral homeo-gene cluster. We show that Hox-1.4, -2.6 and -5.1 are similar, although apparently not identical, in the limits of their transcript domains along the anteroposterior axis. Within the prevertebral column of the 12 1/2 day embryo, for example, the anterior boundary of transcripts for each of the three genes was most obvious at the junction of the first and second prevertebrae. Similarly, all three genes showed an anterior boundary of transcripts within the central nervous system that was located in the mid-myelencephalon of the hindbrain. Both in the prevertebral column and hindbrain, however, Hox-2.6 and Hox-5.1 transcripts extended slightly anterior to the anteriormost limits detected for Hox-1.4. In spite of close similarities in the positions of their transcript domains, Hox-1.4, -2.6 and -5.1 displayed striking stage- and tissue-dependent differences in the relative abundance of their transcripts. For example, Hox-5.1 transcripts were abundant within mesoderm and ectoderm of early stages (8 1/2 and 9 1/2 days), yet were detected only weakly in mesodermal components of the lung and stomach at 10 1/2 days, and were apparently absent from these tissues at 12 1/2 days. In contrast, Hox-1.4 and Hox 2.6 transcripts were relatively weakly detected at 8 1/2 and 9 1/2 days, but were abundant within the lung and stomach at 12 1/2 days. Our findings suggest, but do not prove, that genes within the Hox-1.4 subfamily might be coordinately regulated in their expression. We discuss the patterns of mouse homeo-gene expression now observed in terms of models originally devised for Drosophila. We also propose how our new findings may help to explain any selective advantage to the vertebrates of homeo-gene duplication to form subfamilies. PMID- 2576401 TI - [Effect of various beta-adrenolytic drugs on heart rate and changes in left ventricular systolic time intervals in patients with hyperthyroidism and simple goiter]. AB - The effects of a short-term application of various beta-adrenolytic drugs on heart rate and on the changes in subperiods of left ventricle contraction have been studied in 71 patients with untreated hyperthyroidism and in 72 patients with simple goiter. The following drugs were used: propranolol, metoprolol, atenolol, pindolol, nadolol and acebutolol. It was found that those betaadrenolytic drugs which have no sympathomimetic action cause a significant decrease in heart rate both in patients with hyperthyroidism and in those with simple goiter. The effect of these drugs on heart rate was not related to the changes in blood serum concentrations of thyroxine and triiodothyronine. None of the drugs tested influenced appreciably the contraction subperiods of left heart ventricle, both in the patients with hyperthyroidism and in those with simple goiter. PMID- 2576402 TI - Fat distribution and gamma-glutamyl transferase in relation to serum lipids and blood pressure in 38-year old Dutch males. AB - In this study we describe the associations between indicators of fatness, fat distribution, and alcohol consumption (gamma-glutamyl transferase) with serum lipids and blood pressure in a random selected group (n = 69) of 38-year old men. Waist circumference, subscapular skinfold and body mass index all had similar positive associations with total cholesterol, triglycerides and diastolic blood pressure. Gamma-glutamyl transferase levels were associated with indicators of fatness and fat distribution (waist circumference, waist/hip ratio, body mass index, and subscapular skinfold) and serum lipids (total cholesterol, LDL cholesterol, triglycerides). Gamma-glutamyl transferase and body mass index both made independent contributions to the explanation of the waist/hip ratio. In multiple regression analysis, gamma-glutamyl transferase levels were (after adjustment for waist/hip ratio and body mass index) associated with serum lipids (total cholesterol, LDL-cholesterol, and triglycerides), but not with HDL cholesterol and blood pressure. Body mass index only showed an independent relation to triglyceride levels, whereas the waist/hip ratio was only associated with diastolic blood pressure in multiple regression. It is concluded that gamma glutamyl transferase levels are a potentially important indicator of abdominal fat distribution and unfavourable lipoprotein profiles. PMID- 2576404 TI - The polymorphic human chaperonin protein HuCha60 is a mitochondrial protein sensitive to heat shock and cell transformation. AB - The HuCha60 protein, a polymorphic protein on two-dimensional gels of human lymphocytes, is found to be structurally and functionally related to the Escherichia coli groEL gene product: The structural homology is evident from the N-terminal amino-acid sequence analysis and from the immunological cross reactivity with an antiserum against the E. coli groEL gene product. The functional homology is suggested by the heat sensitivity and the growth dependence of this protein. Both genetic variants of the HuCha60 occurring on the two-dimensional protein pattern of lymphocytes, the common "a" variant and the rare "b" variant, are strongly enhanced after heat shock. The expression of the HuCha60 in resting or normally growing cultures human cells is in general low, whereas in mitogen-stimulated cells or transformed cell lines the synthesis of the HuCha60 is strongly enhanced. After cell fractionation and subsequent two dimensional gel electrophoresis and immunoblotting, the HuCha60 has been found to be mainly expressed in mitochondria. In the cytosol fraction two different molecular weight forms of the HuCha60 have been observed with low expression. Also in the nuclear fraction, HuCha60 is present in low concentration. PMID- 2576403 TI - Effects of capping on the non-ionic detergent solubility of rat thymocyte glycoproteins. AB - The non-ionic detergent solubility of surface antigens during capping, following their cross-linking by specific antibodies, was investigated for three rat thymocyte glycoproteins, the leucocyte-common antigen (L-CA), the leucocyte sialoglycoprotein (LSGP) and Thy-1, using a combination of immunofluorescence microscopy, covalent surface radiolabeling and quantitative analysis using a radiolabeled antibody. Prior to the addition of cross-linking antibody, both L-CA and LSGP were soluble in the non-ionic detergent Triton X-100, while Thy-1 was largely insoluble. Addition of sufficient antibody to induce capping led to a significant reduction in the solubility of L-CA and LSGP, even prior to warming to induce capping of the antigen under investigation. Subsequent capping did not increase the amount of insoluble antigen, suggesting that ligand binding, rather than the process of capping itself, is sufficient to cause this partial Triton insolubility. These results indicate the formation of an association between these liganded glycoproteins and the cell's detergent-insoluble cytoskeleton. In contrast, the Thy-1 antigen became progressively more extractable by Triton X-100 as the antigen was capped, suggesting that the insertion of the Thy-1 lipid tail into the plasma membrane was progressively more easily perturbed by the non-ionic detergent during the capping process. The reciprocal maintenance of solubility of either LSGP or L-CA during the capping of the other shows that the majority of the 180 kDa thymocyte L-CA molecules play no role in the mechanism of capping of LSGP. Furthermore, immunoprecipitates of solubilized L-CA contained no detectable amounts of the cytoskeletal protein fodrin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576405 TI - Chemotherapy for resistant and relapsing multiple myeloma. AB - This report summarizes a broad experience in the treatment of patients with multiple myeloma resistant to standard chemotherapy. The VAD regimen has induced remissions in about 50% of relapsing patients but in only about 25% of previously unresponsive patients. In patients resistant to VAD, high-dose therapies with intravenous melphalan, a CBV combination (cyclophosphamide-BCNU-VP-16) or an EDAP regimen (VP-16 -platinum) produced responses in about 40% of patients. However, these treatments usually required autologous bone marrow or blood stem cell support and the median duration of control was only 6 months. With an even more intensive program using high-dose melphalan and total body irradiation supported by autologous bone marrow, all patients who survived the early treatment period responded for a median duration of about 1 year. Results indicated a dose response effect of chemoradiotherapy on VAD-resistant myeloma with the potential that such intensive regimens will prolong disease-free survival time. PMID- 2576407 TI - [The reactivity and functional heterogeneity of the cerebral arteries]. AB - The reactivity and functional heterogeneity of cerebral arteries are maintained by the participation of the endothelium in the regulation of the smooth muscles and by the influence of vasoactive peptides upon the neurotransmitter mechanisms. The initial level of the basal tone plays a major role, too. PMID- 2576408 TI - [The role of a neurogenic mechanism in regulating cerebral circulation]. AB - The literature and own data on the efferent innervation of cerebral vessels, its sources and the structure of neurogenic regulation of intracranial hemodynamics, are summed up. Diverse mechanisms of the cerebral vessels' innervation involve polymodal efferent fibers and terminals associated with existence of numerous transmitters, the participation of some bulbar nuclei along with the sympathetic system in the innervation. The diversity of the controlling factors seems to be the result of an imperfection of cerebral blood supply system due to its accelerated development in the course of phylogenesis. PMID- 2576406 TI - [Experience in raising the qualifications of the feldsher to render medical care to children]. PMID- 2576409 TI - [The interaction of humoral, metabolic and myogenic regulation of the cerebral circulation in unilateral occlusion of the internal carotid artery]. AB - Transcranial dopplerography revealed an asymmetry in middle cerebral arteries in unilateral occlusion of the inner carotid artery. The reactivity of cerebral vessels to carbonic acid diminishes on the side of the occlusion. In absence of the brain tissue infarction, surgical revascularization leads to a partial normalizing of the reactivity. The data obtained suggests a considerable alteration of the interaction among humoral, metabolic and myogenic regulations of cerebral blood flow in unilateral occlusion of the inner carotid artery. PMID- 2576410 TI - [The role of the oscillation of the tail vessels in unanesthetized rats in regulating the blood flow during heat exposure]. AB - Studies of the changes in the rat tail blood vessels in heating shows a considerable increase in slow oscillation frequency, apart from the rheographic index elevation. The hyperthermic effect became considerably lesser in elimination of these oscillations with ganglio- or adrenoblocking agents. The mechanism of hyperemia in heating associated with modulation of mechanic contractions of vascular smooth muscles, are discussed. PMID- 2576411 TI - [Coupling of inhibitory GTP binding protein to somatostatin receptors on rat cerebrocortical membranes]. AB - We studied the interaction between somatostatin receptors and inhibitory GTP binding protein in rat cerebrocortical membranes. Guanine nucleotides reduced [125I-Tyr1] somatostatin binding to cerebrocortical membranes in a dose-dependent manner with rank order of potency being guanyl-5'-yl-imidodiphosphate (Gpp(NH)p) greater than GTP greater than GMP. Maximum reduction of the binding to 32% of control was observed in the presence of 10(-5) M Gpp(NH)p. Scatchard analysis of the labeled somatostatin binding revealed that the decrease in the binding by Gpp(NH)p was due to the decrease in the binding affinity for somatostatin. Divalent cations, such as Mg++, Mn++, and Ca++, caused an increase in labeled somatostatin binding to membranes with the maximum binding observed at a concentration of 10, 10, 1 mM, respectively. However, Na+ decreased a labeled somatostatin binding in a dose-dependent manner, and half maximum inhibition of the binding was observed at 10 mM Na+. Moreover, Gpp(NH)p and Na+ lowered labeled somatostatin binding in an additive fashion. When cerebrocortical membranes were treated at 37 degrees C for 40 min with various concentrations of Islet Activating-Protein (IAP), which had been preactivated with dithiothreitol, subsequent labeled somatostatin binding to the membranes was decreased in a dose dependent manner. 30 micrograms/ml IAP treatment caused a decrease in the binding to 50% of control, which was characterized by the decreased binding affinity without a significant change in the binding capacity. Furthermore, exposure of IAP plus NAD to cerebrocortical membranes caused ADP-ribosylation of a membrane protein with Mr = 41,000 on autoradiogram. Such an IAP treatment of cerebrocortical membranes abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in adenylate cyclase activity. These results suggest that somatostatin receptors in the brain couple to inhibitory GTP binding protein, which mediates adenylate cyclase inhibition by somatostatin. PMID- 2576412 TI - Association of particulate transglutaminase with the nerve-muscle synapse. PMID- 2576413 TI - Intracellular events responsible for the inhibition of insulin secretion by somatostatin. PMID- 2576414 TI - Characterization of rat liver beta-adrenoceptors during lactation. PMID- 2576415 TI - Effect of chronic alcohol feeding with a low-fat diet on acetyl CoA carboxylase and fatty acid synthase activities in rat liver. PMID- 2576416 TI - Polyadenylation and U7 snRNP-mediated cleavage: alternative modes of RNA 3' processing in two avian histone H1 genes. AB - The six chicken histone H1 genes have 3'-processing sequences typical of replication-dependent histone genes, which are expressed as poly(A)- mRNAs. However, by Northern analysis of RNA from several adult chicken tissues, as well as from embryonal skeletal muscle in vivo and in vitro, we have observed histone H1 transcripts longer than those predicted on the basis of the published genomic sequences. These RNAs are polyadenylated transcripts of the genes H1.01 and H1.10, which encode the 'c fraction' H1 protein subtypes. Both transcripts contain an internal stem-loop and purine-rich box associated with the 3' processing of poly(A)- histone mRNAs. The 2-kb poly(A)+ H1.01 transcript is present at high steady-state levels in tissues with low rates of DNA synthesis, has a longer half-life than the poly(A)- mRNA from the same gene, and is polyribosomal in embryonal skeletal muscle. The 1-kb poly(A)+ H1.10 RNA is the major H1.10 transcript in adult skeletal muscle. The properties of these RNAs suggest that they may contribute to the relaxed replication dependence of c fraction subtype expression. The polyadenylation signals of both genes are unusual in their association with processed (nonhistone) pseudogene-like elements, an arrangement with possible implications for the mechanism of alternative 3'-end formation in these genes. PMID- 2576417 TI - The structural biology of CD2. AB - The CD2 molecule is a 50-55KD transmembrane glycoprotein expressed on the vast majority of thymocytes and virtually all peripheral T lymphocytes. Its functions are two-fold: adhesion and activation. CD2 serves to facilitate conjugate formation between the T-lineage cell and its cognate partner via intermolecular interaction of CD2 and LFA-3 on the former and latter cells, respectively. Perturbation of the CD2 extracellular segment by certain combinations of anti-CD2 MAbs or LFA-3 and a single anti-CD2 MAb activate T-lineage function. These CD2 mediated activation events also synergize with signals mediated through the TCR to augment T-cell response. Based on microchemical analysis of immunoaffinity purified human CD2 and cDNA and genomic cloning of mouse and human molecules, considerable structural information is now available. The mature surface human CD2 molecule consists of 327 amino acids: a 185 aa extracellular segment; a 25 aa hydrophobic transmembrane segment; and a 117 aa cytoplasmic domain rich in prolines and basic residues. The CD2 gene is comprised of five exons which span approximately 12 Kb on chromosome 1. A similar protein structure and gene exon organization is found for the mouse CD2 homologue. The CD2 adhesion domain is approximately 103 aa in length and is encoded by a single exon (exon 2). This domain is resistant to proteolysis, even though it lacks any intrachain disulfides and, like the entire extracellular segment protein expressed in a baculovirus system, binds to its cellular ligand, LFA-3. The latter occurs with a micromolar Kd. This relatively low affinity suggests that multivalent interactions among CD2 monomers on the T cells and individual LFA-3 structures on the cognate partner are important in enhancing the avidity of the T-cell interaction with its target or stimulator cell. The affinity of the CD2 extracellular segment for LFA-3 is not affected by truncations in the CD2 cytoplasmic domain, implying that ligand binding is not regulated by intracellular mechanisms. Given that CD2 mRNA expression and surface CD2 copy number are increased by more than one order of magnitude post-TCR stimulation, it is more likely that adhesion via CD2 is modulated by alteration in surface copy number. Analysis of early transduction events occurring via CD3-Ti (TCR) and CD2 including single channel Ca2+ patch-clamp recordings on living human T lymphocytes indicate a virtual identity of signals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2576418 TI - Activation of T lymphocytes via monoclonal antibodies against rat cell surface antigens with particular reference to CD2 antigen. AB - In the rat, monoclonal antibodies (mAbs) against the T-lymphocyte receptor (TCR), CD3 antigen and CD2 antigen are mitogenic for T lymphocytes. Antibodies against CD43 (leukosialin) and CD5 are not, but can enhance the effects of other stimuli. Activation of a T-lymphocyte cell line in terms of triggering an increase in free cytoplasmic Ca2+ [( Ca2+]i) was mediated by mAbs against Class 1 MHC and CD4 in addition to the mitogenic mAbs. In the presence of non-activating levels of anti TCR mAb a strong synergistic signal was seen with anti-CD4, but incubation with anti-CD4 prior to activation with anti-CD3 inhibited the CD3 signal. Stimulation of DNA synthesis in resting T cells via anti-CD2 mAbs required a combination of two non-competitive antibodies and addition of a third anti-CD2 mAb inhibited the activation. The anti-CD2 mAbs were active on all types of mature T cells from peripheral lymphoid organs and the thymus, but cells in the thymus that lacked a TCR could not be activated via CD2. Rat CD2 was transfected into Jurkat cells and cross-linking with anti-rat CD2 mAbs gave an increase in [Ca2+]i similar to that seen with an anti-human CD3 mAb. All three types of anti-rat CD2 mAbs gave a signal including the mAb that inhibited mitogenesis. Signal transduction via CD2 was not seen in L cells and was only weakly observed in TCR-ve Jurkat cells that had been transfected with rat CD2. The cytoplasmic domain of transfected CD2 was shown to be important for the signal transduction since no increase in [Ca2+]i could be triggered in cells expressing mutant CD2 that lacked the cytoplasmic domain. Mutant forms with increasing lengths of cytoplasmic domain showed functions that progressively approached that of the native function. PMID- 2576419 TI - Restriction fragment length polymorphism: a recent approach in plant breeding. PMID- 2576420 TI - Structure-activity relationships in diphenyl ethers for insect growth regulating activity against mosquitoes. AB - Out of the 30 substituted diphenyl ethers synthesized and tested for insect growth regulating (IGR) activity against mosquitoes, three compounds viz., DPE 16, 19 and 28 showed promising IGR activity. While DPE-16 and 19 were found to be effective against all three vector species tested viz., Culex quinquefasciatus, Aedes aegypti and Anopheles stephensi, with the respective EI50 values of 0.1485, 0.3650, 0.2225 mg/l and 0.1474, 0.1392, 0.1145 mg/l, DPE-28 was found to be highly effective against C. quinquefasciatus with an EI50 value of 0.0022 mg/l. The structure-activity relationship in the diphenyl ethers with respect to their octanol-water partition coefficients showed an increase of lipophilicity when both the ortho positions of the phenolic moiety are substituted by tertiary butyl group. The simulated field trial carried out with DPE-16, 19 and 28 showed that these compounds were effective for 7, 7 and 9 days respectively at 0.1 mg/l against C. quinquefasciatus. PMID- 2576421 TI - Restriction endonuclease analysis of DNA in sickle cell lesions among tribals of Bihar, Madhya Pradesh, Gujarat & Rajasthan. AB - Restriction endonuclease analysis of DNA was undertaken in blood samples from individuals who were normal (110), had sickle cell trait (44) and homozygous sickle cell disease (6) from the tribal populations of Bihar, Madhya Pradesh, Gujarat and southern Rajasthan. DNA was prepared from all the blood samples and processed for restriction enzyme digestion, agarose electrophoresis, prehybridization, Nick-translation hybridization and autoradiography. A polymorphic HpaI restriction endonuclease recognition site on the 3' side of the beta-globin gene was used to analyse to determine the beta-globin gene mutant S. It was found that mutation has resulted within the normal 7.6 Kb HpaI fragment among the tribal populations studied. On comparing the results with those from Middle East and East Africa it appears that the sickle gene mutation in India, Saudi Arabia and Kenya arose separately from that in West Africa. PMID- 2576422 TI - Aggressive behaviour--basic & clinical frontiers. PMID- 2576423 TI - Temazepam withdrawal in elderly hospitalized patients: a double blind randomised trial comparing abrupt versus gradual withdrawal. AB - 31 of 36 elderly mainly confused hospitalized patients (69-98 years) taking temazepam 10 mgs nocte for more than one month completed a double blind randomised placebo controlled trial comparing abrupt versus gradual withdrawal of temazepam. Hours of sleep were recorded for all patients during a 7 day baseline period while taking temazepam 10 mg nocte. Then the abrupt withdrawal (AW) group (n = 15) received placebo for 10 nights and the gradual withdrawal (GW) group (n = 16) received temazepam 5 mg for the first 4 nights, 2 mg for the next 4 nights and placebo for the last 2 nights. There was no significant difference in mean hours of nightly sleep during the baseline period between the AW group (5.9 +/- 1.1 SD) and GW group (5.8 +/- 1.1 SD) and between the baseline and withdrawal periods in each group (withdrawal periods, AW 5.6 +/- 1.2, GW 5.6 +/- 1.0). There was no rebound insomnia when temazepam was withdrawn either abruptly or gradually in long-term hospitalised elderly patients and may not be effective as a long term hypnotic. PMID- 2576424 TI - Chromosome 5 allele loss in human gastric, ampullary and pancreatic carcinomas. AB - Chromosome 5 allele loss is a genetic alteration occurring during the multistep progression of colon carcinogenesis. To determine whether a similar genetic alteration occurs in other gastrointestinal malignancies, the authors have analyzed DNA extracted from freshly frozen normal and neoplastic tissue from nineteen patients who underwent radical resections for gastric, ampullary and pancreatic adenocarcinomas at the University of Chicago. Loss of heterozygosity for alleles on the long arm of chromosome 5 was detected in tumor DNA compared to normal tissue DNA from the same patient using restriction fragment length polymorphisms (RFLPs). Eleven patients were informative using the restriction endonuclease TaqI to generate RFLPs for chromosome 5 probes C11 P11 and pTP5E. Loss of heterozygosity was found in one of eight informative gastric carcinomas (12.5%) and in one of two informative ampullary carcinomas. The only informative pancreatic adenocarcinoma was heterozygous. It is concluded that chromosome 5 allele loss occurs in a variety of gastrointestinal malignancies and suggest that common genetic origins may underlie these different tumors. PMID- 2576425 TI - Association of elevated expression of the c-erbB-2 protein with spread of breast cancer. AB - We analyzed amplification and expression of the c-erbB-2 gene in human breast cancers. Southern blot hybridization analysis demonstrated amplification of the c erbB-2 gene in 10 out of 50 tumor DNAs examined. The degree of amplification was three- to twenty-fold relative to normal placenta. The c-erbB-2 protein could be analyzed in 39 tumor tissues of the 50 samples by immuno-blotting, and elevated expression of the c-erbB-2 protein was found in 15 cases. On the other hand, expression of the c-erbB-2 products was not detected in normal breast tissues either by immuno-blotting or by immuno-histological analysis. These data indicate that transcriptional and/or translational activation of c-erbB-2 might occur in some breast cancers in addition to activation by gene amplification. The elevated expression of the c-erbB-2 protein was most strongly correlated with lymph-node metastasis (P less than 0.001), suggesting that c-erbB-2 expression is involved in promotion of the lymph-node metastasis of human breast cancers. Therefore, immuno-histological diagnosis with anti-c-erbB-2 antibody might be useful as an indicator to predict lymph-node involvement in breast cancer. PMID- 2576426 TI - Further characterization of the human adrenal-derived P-glycoprotein recognized by monoclonal antibody MRK 16 reacting with only human P-glycoprotein. AB - This paper describes further characterization of the 170-180-kDa glycoprotein (P glycoprotein) recognized by the monoclonal antibody MRK 16 in the human adrenal. By electron microscopy, P-glycoprotein was observed in the adrenal cell membranes. However, MRK 16-defined P-glycoprotein was not found in cow, pig, horse, monkey or rabbit adrenal, indicating that MRK 16 recognizes the non homologous part of P-glycoprotein of various species. Eleven out of 16 adrenal tumors including 4 cases of primary aldosteronism and 7 cases of Cushing syndrome were intensely stained with MRK 16, whereas pheochromocytoma, non-functioning adrenocortical adenoma with no associated increase of serum adrenal-derived hormones and myolipoma of the adrenal were not. Finally, P-glycoprotein-MRK 16 protein A-Sepharose complex derived from human adrenal possessed marked ATPase activity. Taken together, these data suggest that P-glycoprotein may play a physiological role in the human adrenal. PMID- 2576427 TI - Cutaneous polyarteritis nodosa: a clinical and histopathological study of 20 cases. AB - Twenty cases diagnosed as cutaneous polyarteritis nodosa (CPN) and confirmed by skin biopsy over the last 17 years were reviewed in our department. Based upon their clinical features, laboratory findings, and long-term observation of the disease course, they were divided into three groups. 1) Group 1 comprised 16 cases which were classified as the mild cutaneous form. The disease was confined to the skin with occasional involvement of peripheral nerves and skeletal muscles of the affected extremity. They generally followed a benign course. 2) Group 2 comprised 2 cases classified as the severe form. Despite severe clinical manifestations and several abnormal laboratory findings, the disease was limited to the skin, muscles, and peripheral nerves without any visceral involvement over follow-up periods of 11 years and 5 years, respectively. 3) Group 3 comprised 2 cases of the progressive form; in these the disease had begun with a cutaneous lesion and progressed to the systemic form after 19 and 18 year periods of recurrent episodes of cutaneous lesions, respectively. One died of gastrointestinal bleeding. In group 3, serum antinuclear antibodies and rheumatoid factor were positive. The autoimmune mechanism seems to play a role in this group. It is clear from the results of this study that not all patients whose vasculitic lesions are apparently limited to the skin remain in a benign course. Long-term follow-up is essential. PMID- 2576428 TI - Changes in pancreatic exocrine secretion after repeated haloperidol administration. AB - The effect of repeated administration of haloperidol on the pancreatic secretion was studied in urethane-anesthetized Swiss mice. Haloperidol (2 mg/kg) injected daily i.p. for 7 days, increase the volume and protein content of the basal pancreatic juice significantly. This secretory activity was partially blocked by i.p. injection of atropine (5 mg/kg), both in control and treated animals. The volume of the secretory response to bethanechol, a cholinergic agonist, was decreased by haloperidol without any change in amylase release. From these findings it is concluded that repeated haloperidol treatment produces an increase of basal pancreatic secretion, which is probably the result of changes in the sensitivity of dopamine receptors of the gland. PMID- 2576430 TI - Remodelling of the heart in DOCA-salt hypertensive rats by propranolol and by an alpha-2 agonist, rilmenidine. AB - The effects of rilmenidine [(N-dicyclopropylmethyl) amino-2-oxazoline; S 3341], an alpha 2 agonist, on the hypertensive rat heart have been compared with those of propranolol, using a model of deoxycorticosterone acetate (DOCA)-salt hypertension. One week after nephrectomy and initial treatment with DOCA-salt, which was continued for an additional 7 weeks, the two drugs were added to the rats drinking water at a concentration of 10 mg/kg per day for rilmenidine and 15 mg/kg per day for propranolol. Both drugs had a slight and similarly significant antihypertensive effect at their respective concentrations [systolic blood pressure in controls, 141 +/- 15 mmHg (n = 20); after DOCA-salt, 209 +/- 22 mmHg (n = 24); after propranolol, 182 +/- 19 mmHg (n = 20, P less than 0.01); after rilmenidine, 192 +/- 15 mmHg (n = 19, P less than 0.05)]. They also lowered the systolic blood pressure x frequency product (P less than 0.001). Propranolol, but not rilmenidine, significantly reduced the left ventricular weight: body weight ratio [in controls, 2.00 +/- 0.2 mg/g; after DOCA-salt, 3.04 +/- 0.5 mg/g; after propranolol, 2.67 +/- 0.4 mg/g (P less than 0.05); after rilmenidine, 3.13 +/- 0.6 mg/g (P = NS)]. However, both propranolol and rilmenidine reduced left ventricular weight [in controls, 676 +/- 57 mg; after DOCA-salt, 827 +/- 114 mg; after propranolol, 732 +/- 108 mg (P less than 0.01); after rilmenidine, 760 +/- 100 mg (P less than 0.05)].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576429 TI - The Na,K-ATPase alpha 2 subunit gene displays restriction fragment length polymorphisms between the genomes of normotensive and hypertensive rats. AB - The Na,K-adenosine triphosphatase (ATPase) alpha 2 subunit gene was found to display restriction fragment length polymorphisms (RFLPs) between the genomes of normotensive and hypertensive rats when digested with the restriction enzymes Bgl II and Hind III. In normotensive rats, we tested the spontaneously hypertensive rat (SHR) and its substrain, the stroke-prone spontaneously hypertensive rat (SHR SP). Rat (SD) complementary (c) DNA encoding the alpha 2 subunit of Na,K-ATPase was used as a probe. When the probe was dissected these RFLPs were found to occur in the vicinity of the genomic locus encoding the middle part of the messenger (m) RNA for the alpha 2 subunit of Na,K-ATPase. A Northern blot analysis indicated that these RFLPs did not influence the alpha 2 subunit with regard to either size or amount of mRNA. PMID- 2576431 TI - Beta-adrenoceptor blockade and sympathetic neurotransmission in the pithed rat. AB - The effects of the beta 1-adrenoceptor blocking drug atenolol and the beta 2 adrenoceptor blocking drug ICI 118551 (ICI, Melbourne, Australia) on noradrenaline release and blood pressure were investigated using the pithed rat, which was subjected to continuous electrical stimulation of the spinal sympathetic outflow (pulses at 3 Hz). This stimulation increased blood pressure but not heart rate. The noradrenaline release rate was calculated by infusing [3H] noradrenaline and measuring the steady-state concentrations of both endogenous and infused noradrenaline. Atenolol (0.2 mg/kg bolus plus 0.1 mg/kg per h, intra-arterially) had no effect on the noradrenaline release rate or heart rate, but significantly decreased blood pressure. On the other hand, ICI 118551 (0.2 mg/kg bolus plus 0.1 mg/kg per h. intra-arterially) had no significant effect on blood pressure or heart rate, but did inhibit the noradrenaline release rate. The sympathoinhibitory effect of ICI 118551 was not observed in animals which had been adrenal medullectomized, suggesting that its effect on noradrenaline release was due to blockade of activation of facilitatory prejunctional beta 2-adrenoceptors by adrenaline. The reduced noradrenaline release in the presence of ICI 118551 was not accompanied by a reduction in blood pressure. This may be because ICI 118551 also blocked vasodilatory beta 2 adrenoceptors on vascular smooth muscle. Indeed, in unstimulated pithed rats, infusions of adrenaline which were non-pressor were found to be pressor after ICI 118551 was administered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576432 TI - Effects of D-timolol on intraocular pressure (IOP), beta blocking activity, and the dynamic changes of drug concentrations in aqueous humor. AB - L-timolol has been used successfully in the treatment of glaucoma. Because of its powerful beta blocking activity, however, more and more side effects have been reported. D-timolol, an optic isomer of L-timolol with much less beta blocking activity, was noted to have similar ocular hypotensive effects through inhibition of aqueous production as L-timolol. Thus, it is expected that D-timolol may reduce the side effects considerably if it is used in the clinics. In this study, we observed the ocular hypotensive effect of 0.5% D-timolol in normotensive and water-loaded rabbits as well as in patients with glaucoma or ocular hypertension. A significant reduction of intraocular pressure (IOP) which lasted at least six hours was observed. No side effects, either locally or systemically, were found. The concentration of D-timolol was traced in rabbits' aqueous humor after topical administration. The drug quickly appeared in the aqueous 30 minutes after instillation of 100 microliters 1% D-timolol. The peak concentration was 1916.5 ng/ml. It declined to a minimum in four hours, although the hypotensive effect could last at least six hours. For estimating the beta blocking potency of D timolol, radioligand binding assay was employed to calculate the Ki value from isolated cell membrane of rabbits' lung. It showed that the beta blocking potency of D-timolol was much less than that obtained from L-timolol. It is concluded that D-timolol may be a valuable antiglaucoma agent comparable to L-timolol in lowering the IOP. The side effects induced by beta blocking agents we are using currently might be considerably reduced with D-timolol. PMID- 2576433 TI - Effects of dopamine antagonists injected through vortex veins on intraocular pressure. AB - In order to avoid the factors of the corneal barrier and tearing washout on absorption of eye drops, dopamine and antagonists were injected into rabbit eyeballs through vortex veins. Many dopamine antagonists, such as haloperidol, moperone, metoclopramide, trifluperidol, lenperone, and fluoropipamide, lowered the intraocular pressure (IOP), whereas a few of them, such as chlofluperol and trifluoperazine, raised the IOP. Furthermore, it was found that dopamine agonists also could either increase or decrease the IOP. The ocular hypertensive effect of dopamine was blocked by haloperidol as expected. However, when the hypotension inducing dopamine agonist, bromocriptine, and antagonist, haloperidol, were combined, the IOP remained unchanged. It was concluded that dopamine agonists and antagonists act at different sites and changes in IOP resulted from a combined summary of these complex effects. As a result, dopamine agonists and antagonists, while they may both lower the IOP when given alone, can antagonize each other through different sites and produce no net change in IOP. PMID- 2576434 TI - Binding of timolol to iris-ciliary body and melanin: an in vitro model for assessing the kinetics and efficacy of long-acting antiglaucoma drugs. AB - Topical beta blockers are used to treat glaucoma patients. These drugs inhibit aqueous production for prolonged periods of time. The purpose of this study was to determine whether timolol maleate (a non-specific beta blocker) binds to human iris-ciliary body (CB) melanin and to elucidate the binding characteristics of the drug to melanin. Timolol bound to bovine iris and ciliary body by two possible mechanisms. The binding kinetics indicate that the binding is probably of a nonspecific nature. There was no statistically significant differences between the melanotic tissues (CB, iris) and the nonmelanotic tissues (lens, cornea, liver, kidney) regarding the amount of timolol bound. However significantly more timolol was bound to the isolated melanins than the whole tissues. Timolol was released from the nonmelanotic tissues at a much faster rate than from the melanotic tissues. The amount of timolol bound to iris-CB from albino and pigmented rabbits showed that the amount of timolol bound to these tissues diminished in the following order: black or gray greater than brown greater than albino. It was also found that the rate of timolol release decreased in the following order: albino greater than gray greater than brown or black. Our results demonstrate the binding of beta blocker to human, bovine and rabbit iris CB and consequent slow release of timolol from these tissues. PMID- 2576435 TI - Recurrent gastroesophageal symptoms and precordial pain in a gastrectomized man improved by amitriptyline. Physiologic, metabolic, endocrine, neurochemical and psychiatric findings. AB - A 57-year-old white man presenting frequent recurrent chest and precordial pain, heartburn (pyrosis) and post-prandial vomiting for the previous 33 years (one to two years after Bilroth II gastrectomy) was submitted to cardiovascular, endoscopic, radiologic and biochemical studies with negative results. Doctors recommended surgical operation because of an excessively long afferent loop, Several biologic markers were performed at our hospital (intestinal pharmacomanometry, i.m. clonidine test, plasma neurotransmitters plus hormones, oral glucose tolerance test, plasma insulin, etc.), revealing an autonomic nervous system (ANS) imbalance characterized by hyperactivity of the cholinergic plus hypoactivity of the noradrenergic central system. Psychiatric evaluation demonstrated Dysthymic Depression. Treatment with a small daily dose of amitriptyline (a drug which enhances central noradrenergic activity and exerts powerful anticholinergic effects) suppressed symptoms, normalized physiological plus hormonal plus neurochemical parameters and made depressive manifestations disappear. The results suggest that the ANS imbalance was related to depressive syndrome and potentiated by neurohumoral disorders depending on duodenal and jejunal exclusion, and on intestinal post-prandial hyper-osmolarity. PMID- 2576436 TI - Polymorphic repetitive DNA sequences in Mycobacterium tuberculosis detected with a gene probe from a Mycobacterium fortuitum plasmid. AB - Clinical isolates of Mycobacterium tuberculosis were shown by Southern blotting to contain DNA sequences hybridizing to a probe derived from a Mycobacterium fortuitum plasmid. Two such M. tuberculosis DNA fragments, isolated from a gene library, were used as probes to show restriction fragment length polymorphism in M. tuberculosis strains by detecting a repetitive sequence apparently located at different points on the chromosome. This could indicate the presence of a transposable element in M. tuberculosis which is partly homologous to a region of the M. fortuitum plasmid. The probes described can be used to fingerprint M. tuberculosis isolates, and in addition are capable of distinguishing M. tuberculosis from Mycobacterium bovis and BCG. PMID- 2576437 TI - Regulation of nitrogen catabolic enzymes in Streptomyces clavuligerus. AB - The levels of several enzymes involved in assimilation of different nitrogen compounds were investigated in Streptomyces clavuligerus in relation to the nitrogen source supplied to the cultures. Threonine dehydratase, serine dehydratase, proline dehydrogenase, histidase and urocanase were not decreased in the presence of ammonium. The latter two enzymes were induced by histidine in the culture medium, while proline dehydrogenase was induced by proline. Glutamine synthetase, urease and ornithine aminotransferase levels were higher with poor nitrogen sources and were repressed by ammonium. Arginase was induced by arginine and repressed by ammonium. Glutamine synthetase was rapidly inactivated upon addition of ammonium to the culture, and could be reactivated in vitro by treatment with snake venom phosphodiesterase, which suggested that adenylylation is involved in the inactivation. Three previously isolated mutants with abnormal glutamine synthetase activities showed pleiotropic effects on urease formation. All these data point to a mechanism controlling preferential utilization of some nitrogen sources in this species. PMID- 2576438 TI - Isolation and characterization of nitrogen-deregulated mutants of Streptomyces clavuligerus. AB - Two screening methods for isolation of mutants of Streptomyces clavuligerus with altered control of nitrogen metabolism enzymes are described. Thirty-eight prototrophic mutants with simultaneous deregulation of urease and glutamine synthetase were isolated. Nine mutants were examined in more detail and they also showed deregulated formation of arginase and ornithine aminotransferase. Different patterns of altered control of all four enzymes were observed. Inactivation of glutamine synthetase after ammonium shock took place to different extents in these nine strains, and seven of them had a thermosensitive glutamine synthetase activity. It is concluded that a system of nitrogen control, in which glutamine synthetase has a key role, is present in S. clavuligerus. Cephalosporin production was depressed by ammonium in all the mutants, irrespective of the alterations in nitrogen control of primary metabolism. PMID- 2576439 TI - The identification of Candida albicans strains by restriction fragment length polymorphism analysis of DNA. AB - Digestion of total DNA from Candida albicans isolates with the restriction enzyme HinfI generated simple, readily interpretable band patterns on ethidium bromide stained gels. The procedure, which was highly reproducible, was used to detect restriction fragment length polymorphisms in 47 isolates of this species. PMID- 2576440 TI - The uptake and translocation of latex nanospheres and microspheres after oral administration to rats. AB - Non-ionic and carboxylated fluorescent polystyrene microspheres (100, 500 nm, 1 and 3 microns in diameter), were fed by gavage (2.5% w/v; 1.25 mg kg-1) daily for 10 days to female Sprague Dawley rats. Peyer's patches, villi, liver, lymph nodes and spleen of animals fed the non-ionic microspheres from 100 nm to 1 micron showed unequivocal evidence of uptake and translocation of the particles. Heart, kidney and lung showed no evidence of the presence of microspheres. Carboxylated microspheres were taken up to a lesser degree than the non-ionised particles. Experiments with 125I radiolabelled 100 nm and 1 micron particles showed a higher uptake of the smaller particles, which were concentrated in GI tissue and liver. Particles were not distributed randomly in the tissues, but were concentrated at the serosal side of the Peyer's patches and could be seen traversing the mesentery lymph vessels towards the lymph nodes. The results demonstrate a need to re-examine the possibilities of particulate oral delivery, as well as the potential toxicity of ingested particulates. PMID- 2576441 TI - Albumin microspheres as vehicles for the sustained and controlled release of doxorubicin. AB - Biodegradable albumin microspheres have been prepared with the intention of targeting doxorubicin preferentially to tumour tissue. A high-yielding microsphere manufacturing process has been developed that involved the denaturation of an aqueous protein emulsion by chemical and/or thermal crosslinking methods. Microspheres can be closely sized to a diameter of 25.3 +/- 2.6 microns with the aid of micro-sieves. The in-vitro release of doxorubicin from albumin microspheres was measured using a continuous flow system. Doxorubicin release can be sustained for up to 10 days and the rate of release could be controlled by manipulating protein denaturation conditions between the temperatures 110-135 degrees C in the presence of 0-2% glutaraldehyde. Release of doxorubicin was significantly faster in human plasma compared with isotonic saline. PMID- 2576442 TI - Effect of auranofin on ion transport by rat small intestine. AB - Auranofin, applied either mucosally or serosally, increased the potential difference and short-circuit current generated by stripped sheets of rat mid intestine in a concentration-dependent manner. In-vivo auranofin induced a net fluid secretion, suggesting that the rise in electrical activity represented a stimulation of anion secretion. Removal of chloride or addition of frusemide inhibited the auranofin-induced increase in short-circuit current, indicating that chloride was the anion involved and in the case of serosal auranofin this was confirmed by direct measurement of ion fluxes. The effects of both mucosal and serosal auranofin were calcium-dependent. The gold component of the auranofin molecule is probably responsible for its secretory actions as these were mimicked by chlorauric acid. The ability of auranofin to stimulate intestinal secretion may contribute to its diarrhoeagenic action. PMID- 2576444 TI - Pharmacokinetics of 2',3'-dideoxycytidine in rats: application to interspecies scale-up. AB - The effects of dose on the pharmacokinetics of 2',3'-dideoxycytidine (DDC), a potent inhibitor of HIV replication, have been studied in rats. DDC was administered intravenously at doses of 10, 50, 100 and 200 mg kg-1. Plasma and urine drug concentrations were determined by HPLC. Non-compartmental pharmacokinetic parameters were calculated by area/moment analysis. DDC plasma concentrations declined rapidly with a terminal half-life of 0.98 +/- 0.18 h (mean +/- s.d.). No statistically significant differences were observed in pharmacokinetic parameters between the four doses. Total, renal and non-renal clearance values were independent of dose and averaged 1.67 +/- 0.24, 0.78 +/- 0.11, and 0.89 +/- 0.27 L h-1 kg-1, respectively. Approximately 50% of the dose was excreted unchanged in urine. Steady state volume of distribution was also independent of dose and averaged 1.2 +/- 0.21 L kg-1. Protein binding of DDC to rat serum proteins was independent of drug concentration with the fraction of drug bound averaging 0.45 +/- 0.12. Thus, the disposition pattern of DDC in the rat is independent of the administered dose even at high doses. Significant interspecies correlations were found for total, renal and non-renal clearance and steady state volume of distribution. Interspecies scaling resulted in superimposable plasma DDC concentration-time profiles from four laboratory animal species and man. Thus, plasma DDC concentrations in humans can be predicted from pharmacokinetic parameters obtained in laboratory animals. PMID- 2576443 TI - [3H]acetylcholine release from the guinea-pig distal colon: comparison with ileal [3H]acetylcholine release and effect of adrenoceptor stimulation. AB - To study cholinergic function in the guinea-pig colon, resting and electrically evoked 3H release after preincubation with [3H] choline has been compared in colonic and ileal myenteric plexus preparations. Fractional spontaneous colonic 3H release was significantly higher than ileal 3H release, while the reverse was true for electrically evoked 3H outflow. Electrically evoked 3H outflow in the colon was linearly related to stimulation frequency (0.2-3 Hz range) and current intensity (300-600 mA range), while 3H outflow per pulse was inversely related to stimulation frequency. Electrically evoked 3H outflow was prevented in Ca2(+) free solution, indicating that it probably mirrored neuronal exocytotic [3H]acetylcholine release. Both noradrenaline and clonidine concentration dependently inhibited electrically evoked 3H outflow, clonidine being more potent but less efficacious than noradrenaline. For both noradrenaline and clonidine, the potency and efficacy for inhibition of 3H outflow were close to the values previously reported for the inhibition of electrically evoked endogenous acetylcholine output from colonic preparations. In conclusion, these data indicate that 3H release after incubation with [3H]choline is a valid alternative to measurement of endogenous acetylcholine output to study colonic cholinergic neuronal function in the guinea-pig. PMID- 2576445 TI - Anaesthetic concentrations of enflurane and methoxyflurane in rat brain in-vivo and in-vitro. AB - We measured concentrations of enflurane and methoxyflurane in brains of anaesthetized rats and established conditions for reproducing these concentrations in brain tissue in-vitro. Despite a 12-fold difference in inspired potency, brain concentrations resulting in anaesthesia were similar for both compounds. However, substantially lower concentrations in the equilibrating gas were necessary to achieve similar tissue concentrations in-vitro, probably because anaesthetic-induced respiratory depression or changes in cardiac output causes incomplete equilibration in-vivo. These studies provide direct evidence that brain concentrations associated with anaesthesia are similar for anaesthetics with different inspired potencies. They also suggest that lower concentrations in the equilibrating gas should be used in-vitro to reproduce clinically relevant tissue concentrations that are necessary to cause anaesthesia in-vivo. PMID- 2576447 TI - Correlation between hydrophobicity of N-alkylxanthine derivatives and their biological activities on guinea-pig isolated tracheal smooth muscle. AB - Cyclic (c) AMP phosphodiesterase (PDE) inhibitory activities of N-alkylxanthine derivatives (3-methyl-,3-ethyl-,3-propyl-,3-butyl-,1,3-dimethyl-,1-methyl-3-ethyl ,1-methyl - 3-propyl- and 1-methyl-3-butyl xanthines) and their relaxant effects on carbachol-induced contraction and on resting tone guinea-pig isolated tracheal smooth muscle have been investigated. The PDE inhibition constant (Ki) and the concentration producing 50% tracheal smooth muscle relaxation in-vitro (EC50) were determined. Significant correlations between the -log Ki values and the -log EC50 values on the carbachol-induced contraction or on the resting tone were found (r = 0.902 and 0.892). The apparent partition coefficient (P) between n octanol and pH 7.4 phosphate-buffered saline (PBS) was measured as an index of hydrophobicity of the xanthine derivatives. There were significant correlations between log P and both -log EC50 values and between the log P and -log Ki values. These findings suggest that the cAMP PDE inhibitory activity of N-alkylxanthine derivatives contributes to the mechanism of bronchodilatory action, and that an increase in hydrophobicity of the xanthine molecule enhances the biological activity. PMID- 2576446 TI - An in-vitro study of the interactions between intravenous induction agents and the calcium antagonists verapamil and nifedipine. AB - Thiopentone, propofol and etomidate inhibit the contractions of the rat isolated atria and portal vein. The actions of thiopentone and propofol summate with those of verapamil and nifedipine. Verapamil potentiates the action of etomidate on both preparations. The depressant actions of thiopentone and propofol on the portal vein are associated with a reduced response to calcium. Etomidate does not reduce the response to calcium in this preparation. PMID- 2576449 TI - Characteristics of hydrogel as disintegrant in solid dose technology. AB - A comparison between a hydrogel and the disintegrants Ac-di-sol, Avicel, maize starch and Primojel has been made using theophylline as the test drug in direct compression tableting. Results indicate that the disintegrant action of the hydrogel is comparable with that of the other disintegrants used, with no adverse effect on the dissolution of theophylline from these tablets as observed by thermal analysis study. The hydrogel's physicomechanical performance in direct compression processing appears to have no undesirable effect on the physical properties of tablets. Scanning electron micrographs of freeze-etched samples of hydrogel demonstrated its internal structure. These results strongly suggest that hydrogels have great potential as efficient disintegrants in solid dosage formulations. PMID- 2576448 TI - In-vitro characterization of blood-brain barrier permeability to delta sleep inducing peptide. AB - The diffusion of delta sleep-inducing peptide (DSIP) across the blood-brain barrier (BBB) has been investigated with an in-vitro model comprised of primary cultures of brain microvessel endothelial cell (BMEC) monolayers. The BMEC monolayers were mounted in a side-by-side diffusion apparatus and the transendothelial flux of DSIP analysed by HPLC with UV detection at 280 nm. The transendothelial flux of the peptide was linear with time and increasing concentrations of DSIP (non-saturable), but was not altered by reduced temperature. The apparent permeability coefficient for DSIP penetration of BMEC monolayers was in a range similar to water-soluble substances (e.g. fluorescein, fluorescein isothiocyanate dextrans) that penetrate the blood-brain barrier to a limited degree based on molecular weight. DSIP flux across the BMEC monolayers was also found to be bidirectional, insensitive to metabolic inhibitors, and not altered by high concentrations of tryptophan. Little degradation (apparent t1/2 about 10 h) of DSIP to major metabolites, tryptophan (trp) and des-trp DSIP, occurred over the time of the diffusion experiments. The results of these studies support and confirm observations in-vivo indicating that intact DSIP crosses the BBB by simple transmembrane diffusion. PMID- 2576450 TI - Ionization constants, octanol partition coefficients and cholinesterase inhibitor constants for chlorpromazine and its metabolites. AB - The relationship between the lipophilic character of chlorpromazine and seven of its metabolites and their ability to inhibit horse serum cholinesterase (Ki) has been investigated. Log(1/Ki) values were correlated with log P octanol partition coefficients (r = 0.88, P less than 0.01, n = 8). The inhibitor values ranged from 2.7 x 10(-6) M for chlorpromazine to 48.6 x 10(-6) M for monodesmethylchlorpromazine sulphoxide. Ionization constants were determined by limiting solubility, spectrophotometry and pH-partition characteristics. Demethylated metabolites were more basic than the tertiary amines and the sulphoxides were slightly less basic than the corresponding sulphides. PMID- 2576451 TI - Increased influence of endothelium in obese Zucker rat aorta. AB - The ability of endothelium to alter contractile events in phenylephrine (PE) triggered contraction has been tested on ring segments of the thoracic aorta removed from obese Zucker rats (plasma cholesterol 3.63 mM; n = 8) and from age matched lean rats (plasma cholesterol 2.38 mM; n = 8). In normal medium, PE (1 microM) elicited similar contractions in endothelium-denuded arteries of both strains. However, the presence of endothelium reduced these contractile events and the endothelium-dependent relaxation induced by carbachol (10 microM) was higher in obese rats. In rings incubated in Ca2+ free medium containing EGTA (1 mM), PE (1 microM) induced a phasic contraction and a sustained contraction following addition of Ca2+ (2.5 mM) to the medium. The phasic contraction was due to intracellular Ca2+ release, whereas the sustained response was dependent on extracellular Ca2+ influx. In endothelium-free preparations, the size of both the phasic and sustained contraction was similar for the two strains. The Ca2+ antagonist gallopamil (1 microM) reduced the sustained contraction of lean (24%) and obese (34%) rats without affecting the phasic contraction. In preparations possessing endothelium, the sustained, but not the phasic contraction, of both strains was inhibited. This inhibitory effect of endothelium on the sustained contraction was significantly higher in obese than in lean rats. Thus, it can be concluded that phenylephrine elicited quantitatively and qualitatively similar contractions in obese and lean rats. In both strains, the endothelium diminished the contraction induced by PE, however, this effect was more pronounced in obese rats than in lean ones. These results may explain, in part, the described absence of atherosclerotic lesions in the obese strain. PMID- 2576452 TI - Apparent down-regulation of rat brain mu- and kappa-opioid binding sites labelled with [3H]cycloFOXY following chronic administration of the potent 5 hydroxytryptamine reuptake blocker, clomipramine. AB - This study examined the effect of chronic clomipramine administration on opioid mu- and kappa-binding sites. Clomipramine (5 mg kg-1 day-1) or saline was administered to rats via osmotic minipumps for 3 days or 28 days. Lysed-P2 brain membranes were prepared and preincubated for 60 min without (control membranes) or with 1 microM of the mu-selective acylating agent, 2-(4-ethoxybenzyl)-1 diethylaminoethyl-5-isothiocyanatobenzimid azole-HC1 (BIT), to deplete membranes of mu-binding sites. [3H]6-Desoxy-6 beta-fluoronaltrexone ( [3H]cyclo FOXY) was used to label mu and kappa-binding sites. Weighted nonlinear least squares analysis of cycloFOXY binding surfaces permitted determination of the Kd and Bmax values of mu- and kappa-binding sites in control and treated rats. Subacute (3 days) administration of rats with clomipramine had no significant effect on [3H]cycloFOXY binding. Chronic (28 days) administration of clomipramine produced a small (approximately 10%) but statistically significant decrease in the Bmax. These findings are discussed in reference to other studies that have examined the effect of chronic antidepressant administration on opioid receptors, and speculate that the endogenous opioid systems may play a role in obsessive compulsive disorder. PMID- 2576453 TI - Salivatory effects induced by pirenzepine, atropine, metacine and hexamethonium in preganglionar chronically denervated human parotid gland. AB - Both classical (atropine) and non-traditional (pirenzepine, metacine) antagonists of the muscarinic cholinoreceptors induce, rather than block, an intense and prolonged salivary response in chronically denervated human parotid glands and thus are capable of discriminating between neuronal and aneuronal receptors. Hexamethonium (benzohexonium) a ganglion-blocking agent (0.4 mL, 2.5%) completely inhibits this paradoxical salivation to atropine, benzilylcholine (metacine) and pirenzepine in the chronic preganglionically denervated human parotid gland. The authors discuss the essence of the revealed paradoxical phenomena. PMID- 2576454 TI - Excretion of proguanil in human saliva. AB - After a single oral administration of a 300 mg dose of proguanil to six volunteers, the presence of the drug in saliva was established by chromatographic and spectrophotometric methods. The tmax and elimination half-life of proguanil derived from salivary levels were 4.0 +/- 1.26 h and 15.1 +/- 1.8 h, respectively. These results are in agreement with values previously reported for the drug using plasma level data. The mean saliva: plasma proguanil concentration ratio was 0.41 +/- 0.17 and this was not time dependent. There was a correlation (r = 0.82) between the saliva and simultaneous plasma proguanil concentration. The results suggest that proguanil is passively secreted into saliva and that saliva levels may be useful in the determination of pharmacokinetic parameters and the therapeutic monitoring of the drug. PMID- 2576455 TI - Sustained release of buserelin acetate, a luteinizing hormone-releasing hormone agonist, from an injectable oily preparation utilizing ethylated beta cyclodextrin. AB - The possible use of heptakis (2,6-di-O-ethyl)-beta-cyclodextrin (DE-beta-CyD) as a parenteral sustained-release carrier for buserelin acetate, a luteinizing hormone-releasing hormone superagonist, has been examined. The in-vitro release of buserelin from the oily suspension was significantly retarded by the complexation with DE-beta-CyD, mainly due to the poor water solubility of the complex. A single subcutaneous injection of the suspension containing the buserelin-DE-beta-CyD complex to rats provided an effective continuous plasma level of buserelin lasting for at least one month, indicating a potential therapeutic efficacy for the treatment of the endocrine-dependent diseases. These results suggest that DE-beta-CyD serves as an injectable sustained-release drug carrier suitable for chronic treatment with buserelin acetate. PMID- 2576456 TI - Supersensitivity of atherosclerotic rabbit aorta to ergometrine is mediated by 5 HT2 receptors. AB - The concentration response curve of ergometrine in aortae from rabbits fed a high cholesterol diet for 12 weeks is biphasic. The first phase of the biphasic curve is antagonized by ketanserin, spiperone and cyproheptadine, but not by prazosin. pKB values are compatible with a 5-HT2 receptor mediated effect. The second phase is shifted to the right by prazosin, ketanserin and spiperone but not by cyproheptadine. In this case the pKB values are compatible with an alpha 1 adrenoceptor mediated effect. The concentration response curves for ergometrine and phenylephrine in aortae from control rabbits are monophasic and pKB values again indicate an alpha 1-adrenoceptor mediated response. Thus, ergometrine contracts the aortae of normal and cholesterol-fed rabbits via activation of alpha 1-adrenoceptors. The supersensitivity observed in atherosclerotic strips seems to reflect the appearance of a high affinity component mediated by 5-HT2 receptors. PMID- 2576457 TI - A simple intravenous infusion method in rodents for determining the potency of anticonvulsants acting through GABAergic mechanisms. AB - A simple method of intravenous infusion of convulsant drugs (pentetrazol and bicuculline) into the tail vein of rats has been used to determine seizure threshold and construct log-dose seizure threshold response curves for several anticonvulsant drugs (diazepam, phenobarbitone, pentobarbitone, chlormethiazole and valproate). It has been shown that an index of the dose required to increase seizure threshold by 50% (TI50) can be obtained using small numbers of animals. The advantages of this method over that of the subcutaneous pentetrazol method are several: small numbers of animals required, speed and reproducibility. The data also demonstrate the concordance between TI50 values obtained using pentetrazol and bicuculline as the convulsant agent. It is suggested that this method can be used routinely in screens of anticonvulsant drugs thought to work through GABAergic mechanisms. PMID- 2576458 TI - Effect of long-term treatment with beta-blocker on cardiac hypertrophy in SHR. AB - Recent studies suggest that beta-blocker treatment may attenuate cardiac hypertrophy induced by pressure overload in the spontaneously hypertensive rat (SHR), but the effect of this therapy on the reconstitution of the intracellular constituents in the heart that occurs during the development of cardiac hypertrophy has not been examined. In this study, we investigated the effect of chronic administration of carteolol (4 mg/kg/day p.o.) or propranolol (20 mg/kg/day p.o.), beta-blockers with distinct modes of action, on the composition of cardiac myosin isozymes and histological findings as well as heart weight. Therapeutic periods were 4, 12 or 30 weeks. Though blood pressure was not significantly reduced, the development of cardiac hypertrophy was suppressed as evidenced by left ventricular weight in both groups of carteolol- and propranolol treated SHR for all therapeutic periods. Again, beta-blocker treatment for 12 weeks alleviated myocardial degeneration and reactive fibrosis which were observed in all cases of age-matched untreated SHR. However the extent of the transition of cardiac myosin isozymes from V1 to V2 or V3 were essentially the same among all groups including untreated SHR. These results indicate that chronic administration of beta-blockers attenuates the development of cardiac hypertrophy and degeneration without affecting the transition of myosin isozymes which is thought to be a kind of biochemical adaptation of the myocardium to overload. PMID- 2576459 TI - Angiotensin converting enzyme inhibitor ingestion in children. AB - The effect of angiotensin converting enzyme inhibitors on children is not well documented. A recent increase in popularity of the angiotensin converting enzyme inhibitors has resulted in an increased availability in the home with resulting heightened probability of accidental ingestion of angiotensin converting enzyme inhibitors by children. In response to this we did a retrospective study of angiotensin converting enzyme inhibitor ingestions in children (ages 1-5 years) from two regional poison centers certified by the American Association of Poison Control Centers. The records of the Delaware Valley Regional Poison Control Center and the New Jersey Poison Information Education Systems were reviewed for 1986 and 1987. Forty-eight angiotensin converting enzyme inhibitor exposures in children 1-5 were identified. Twenty exposures (12.5-300mg captopril, 5-15mg enalapril) were managed with syrup of ipecac in a hospital emergency room. All 20 remained asymptomatic for their stay. None required admission to the hospital. Seven exposures (12.5-75mg captopril, 5-10mg enalapril) were managed at home with syrup of ipecac and 1-, 4-, 24-hour follow up by telephone. All 7 remained asymptomatic. 16 exposures (12.5-100mg captopril, 5-30mg enalapril) were managed by phone at home with observation alone and 4-6 hour follow up. All 16 remained asymptomatic. Five exposures were lost to follow up. A larger series is needed to determine risk, but home monitoring seems adequate for children ingesting no more than the therapeutic dose for adults (12.5-100 mg captopril, 5-30 mg enalapril). PMID- 2576460 TI - [Standardization of a method for determining the irritability of mosquitoes (Diptera, Culicidae) to insecticides]. AB - The method for determining mosquito irritability with insecticides recommended by the WHO has some drawbacks, which make the results less valuable. An improved method for determining the irritability is developed, in which WHO standard instruments and WHO insecticide paper are applied. It is suggested that the same specimens be used both in experiment and control, and spontaneously active females be removed from the experiment. It is recommended to calculate mosquito distribution from the degree of irritability. In determining the degree of irritability some motor activity in between flights should be taken into account. In each group average number of flights is calculated within 10 min. contact with insecticide. It is shown that a single experiment with every population is sufficient for obtaining true results if the size of experimental sample is 50 females. PMID- 2576461 TI - [Multiyear ecologic faunistic research on Culicidae in Dnepropetrovsk Province. 1]. AB - Hydrologic characteristic of Dnepropetrovsk, which is situated in drought steppe zone, is presented. Comparative study of bloodsucking mosquito fauna in 4 regions of the town with different urbanization degree was carried out. The fauna in a town differs considerably from natural biotopes. Penetration of forest-steppe and forest mosquitoes into town is explained by the features of the microclimate and hydrologic status of the town. Active season of some species lasts longer in town conditions. Higher density of mosquito larvae is marked in town ponds. The poorest fauna is in regions with dense construction (1st degree of urbanization as stated by WHO), where Culex pipiens molestus dominate. In a region with park forest plantations (2nd degree of urbanization) Aedes cantans, usual for forest zone, dominate. PMID- 2576462 TI - Cryptic human growth hormone gene sequences direct gonadotroph-specific expression in transgenic mice. AB - Our laboratory reported previously that chimeric genes encoding either rat somatostatin (SS) or human GH (hGH), but containing the identical mouse metallothionein-I (MT) promoter/enhancer sequences and hGH 3'-flanking sequences, were selectively expressed in the gonadotrophs of transgenic mice. The experiments reported here were designed to identify the DNA sequences responsible for this unexpected cell-specific expression within the anterior pituitary. We produced new transgenic mice expressing fusion genes that tested separately the requirement of the MT or 3'-hGH sequences for gonadotroph expression. A fusion gene that retained the original MT and SS sequences, with a simian virus 40 polyadenylation signal exchanged for the 3'-hGH sequences, no longer directed strong pituitary expression, but was active in the liver. In contrast, a cytomegalovirus promoter/enhancer-SS-hGH fusion gene was expressed at the same high level in the anterior pituitaries of transgenic mice as the originally studied MT-SS-hGH gene. Immunohistochemical analysis indicated that pituitary expression of the cytomegalovirus promoter/enhancer-SS-hGH fusion gene was also restricted to gonadotroph cells in adult mice. These studies indicate that sequences within the 3'-flanking region of the hGH gene can direct expression of chimeric genes to pituitary cells that do not normally produce growth hormone. PMID- 2576463 TI - Displacement of excitatory amino acid receptor ligands by acidic oligopeptides. AB - A number of L-glutamyl and L-aspartyl dipeptides, glutathione, gamma-D glutamylglycine and gamma-D-glutamyltaurine, were tested for their efficacy to displace ligands specific for different subtypes of excitatory amino acid receptors from rat brain synaptic membranes. In general, the L enanthiomorphs of gamma-glutamyl peptides were more potent displacers than gamma-D-glutamylglycine and -taurine but the latter were more specific for the quisqualate type of receptors. gamma-L-glutamyl-L-glutamate was the most effective dipeptide in displacing the binding of glutamate, 2-amino-3-hydroxy-5-methylisoxazole-4 proprionate (AMPA) and 2-amino-5-phosphonoheptanoate (APH), whereas gamma-L glutamyl-L-aspartate was the most effective in the binding of kainate. Both oxidized and reduced glutathione were inhibitory, being most potent in the binding of AMPA. gamma-L-Glutamylaminomethylsulphonate was most effective in the binding of APH. The most potent gamma-L-glutamyl peptides (glutathione, gamma-L glutamyl-L-glutamate, -L-aspartate, and -glycine) may act as endogenous modulators of excitatory aminoacidergic neurotransmission. PMID- 2576465 TI - Endogenous opioid peptides and farm animal reproduction. PMID- 2576464 TI - [Current indications for percutaneous transhepatic cholangiography (PTC)]. AB - Percutaneous transhepatic cholangiography (PTC) showed its widest diffusion during the late '70s while since the early '80s it was gradually replaced by endoscopic retrograde cholangiopancreatography (ERCP). Anyway, a well definite role for PTC still exists. PTC was performed in 60 of 131 cases of obstructive disease of the biliary tree: the indications are illustrated in detail. The statistical indicators utilized to choose this examination were: echographic determination of the diameter of the biliary tree, bilirubinemia, alkaline phosphatase (ALP) and serum gamma-GT. Data collected during this study showed that biliary dilation has a significant correlation to serum levels of ALP, while bilirubin has not. Biliary dilation is currently well established by echography: in some instances, however, biliary obstruction is earlier suggested by elevated serum enzymes of biliary stasis, while it is clearly demonstrated that biliary dilation is a precursor of jaundice, better defined as an expression of biliary hypertension. Based on these observations and on the review of the literature, the Authors believe that PTC still remains a second choice examination as compared to ERCP: when the latter be not effective for diagnosis or decompression of the biliary tree, then PTC can be resolutive. PMID- 2576466 TI - Pharmacokinetics in pregnancy and placental drug transfer. AB - Total body water increases in pregnancy and while the uterus, placenta, fetus, and amniotic fluid constitute part of this increase, the largest component is in the extracellular water. Fat stores also increase and thus the distribution volumes of all drugs expand, but the major effect is seen in polar drugs which are confined to the extracellular space. Cardiac output and renal function also increase and elimination of polar drugs is accelerated. In contrast, the elimination of lipophilic drugs may be retarded, and the effect on intermediate drugs is variable. Polar drugs cross the placenta slowly and accumulate in amniotic fluid and therefore in the fetal gut lumen. Lipophilic drugs cross the placenta rapidly and their transplacental distribution is dependent on relative maternal and fetal affinity: this is determined largely by protein binding on either side of the placenta. The fetus and neonate dispose of all drugs less rapidly than adults, the most efficient elimination processes being sulphate conjugation and renal excretion. PMID- 2576467 TI - [The hormonal and mediator imprinting of neuroendocrine pathology]. PMID- 2576469 TI - [Somatostatin-like activity (SLI) in the blood during metformin treatment of obese patients with diabetes mellitus type 2]. AB - Plasma somatostatin-like activity (SLI) was measured in obese women with type 2 diabetes in fasting condition and after a test meal (714 kcal: 27% carbohydrates, 8% protein, 73% fat). The tests were done twice: first, after a week of dietetic treatment and then 7 days of metformin administration, 1.5 g a day. Blood glucose and insulin concentration (IRI) were also followed throughout the test. The plasma SLI on fasting and after the test meal, before and after treatment with metformin did not show any significant differences. Blood glucose was lower in the fasting state significantly and serum insulin showed a tendency to decrease at the end of the test. These findings contradict the hypothesis of a possible role of somatostatin in peripheral blood in the enteric effect of metformin. The local (paracrine?) action of SLI secreted after metformin administration cannot be excluded. PMID- 2576468 TI - [Digestive enzyme activity during immobilization stress and its pharmacologic correction with adrenoblockaders]. AB - The change from relative digestive rest to the phase of digestion is characterized by various dynamics of the activity of enterokinase, amylase, and intestinal isoenzyme of alkaline phosphatase. The effect of the food stimulus in 3-hour immobilization can be considered antistress because the activity of the intestinal enzymes is almost the same as that in intact animals. It was found that the intestinal digestive enzymes become adapted to repeated short-term immobilization stress. Administration of alpha- and beta-adrenergic blocking agents changes the response of the digestive enzymes to stress by lowering their activity. PMID- 2576470 TI - Hantavirus-related acute interstitial nephritis in western Europe. Expansion of a world-wide zoonosis. AB - We report the clinical, biological and serological characteristics of 76 cases of Hantavirus-induced acute interstitial nephritis diagnosed in Belgium and France between 1977 and 1986. The disease is characterized by a fever of sudden onset promptly accompanied by pain in the loin or abdomen, nausea and vomiting, myalgias and occasionally with acute myopia and conjunctival injection. Within a week acute renal failure develops, necessitating haemo- or peritoneal dialysis in up to 10 per cent of patients. Transient proteinuria, microscopic haematuria and leukocyturia are observed simultaneously. Thrombocytopenia and mild elevations of hepatic enzymes, LDH and CPK, as well as biological signs of acute inflammatory reaction are observed, lasting for a few days. Spontaneous complete recovery is the rule. This picture is virtually identical with that of nephropathia epidemica, a Hantavirus nephropathy observed in northern Europe. This conclusion is supported by the observation of elevated antibody titres against the Puumala virus, the agent of nephropathia epidemica. This rodent-borne infection is markedly milder than that caused by other Hantaviruses such as the Hantaan or the Seoul virus in Asia. Acute interstitial disease due to Hantavirus should be included in the differential diagnosis of febrile acute renal failure. PMID- 2576471 TI - [Current approaches in the treatment of Parkinson disease]. AB - The latest improvements in Parkinson's disease therapy are reviewed with particular emphasis on the management of long-term treatment syndrome, which has become the chief problem for Parkinson patients since the introduction of levodopa. Current research is directed at overcoming this effect by 1) combining levodopa with new dopamine agonists such as cabergoline or terguride, which have useful pharmacological properties; 2) administering the drugs in different ways to improve their bioavailability (intravenous or subcutaneous infusion); 3) understanding the neurobiological implications of cellular brain grafting; 4) safely transferring the surgical procedure from the experimental to the clinical field. PMID- 2576472 TI - Effects of non-genotoxic hepatocarcinogens phenobarbital and nafenopin on phenotype and growth of different populations of altered foci in rat liver. AB - Non-genotoxic hepatocarcinogens share the ability to induce liver growth in rodents. Phenobarbital (PB), as one prototype compound, promotes the development of liver tumors; altered cell foci of the clear-eosinophilic phenotype, also identified by gamma-glutamyltransferase expression, appear to be precursor lesions. These foci seem to over-respond to the growth-inducing effect of PB. In contrast, the question as to whether peroxisome inducers are also tumor promoters is still unsettled. We will present evidence which strongly suggests that the peroxisome inducer, nafenopin (Naf), promotes tumor development in rat livers by stimulating selective growth of a hitherto undescribed subtype of altered foci. This subtype is characterized by weak diffuse cytoplasmic basophilia of its hepatocytes. Initiation in rats by aflatoxin B1 followed by promotion with Naf produced numerous adenomas and carcinomas; their morphology resembled that of the weakly basophilic foci. Both clear-eosinophilic and weakly basophilic foci appear "spontaneously" in the liver of aging rats. Promotion of such lesions by PB-type compounds or peroxisome inducers may explain cancer formation by these non genotoxic agents. PMID- 2576473 TI - [Tubulointerstitial changes in patients with a history of hemorrhagic fever with renal syndrome]. AB - Altogether 85 patients with a history of hemorrhagic fever and the nephrotic syndrome (HFNS) were examined at different stages after the disease, characterizing the status of the tubulointerstitial apparatus of the kidneys. Almost half of the patients who suffered this disease manifested a decrease in the capacity of the kidneys for osmotic concentration of urine under the conditions of deprivation for 36 hours, and in acid-secretory function of the kidneys under induced acidosis and clearance of uric acid. Ultrasonic studies demonstrated that part of the patients had uni- or bilateral indurations in the renal parenchyma. In 16% of the examined, these alterations may be related to superaddition of pyelonephritis after HFNS. The nature of tubulointerstitial lesions remains unknown in other cases and thus requires a further study. The recovery of tubular functions of the kidneys following HFNS continues for 3 years. In view of this fact patients with a history of this disease need prolonged follow-up. PMID- 2576474 TI - A DQA1 allele is strongly associated with idiopathic membranous nephropathy. AB - The high molecular weight genomic DNA from 31 patients with idiopathic membranous nephropathy (IMN) has been digested with a restriction endonuclease Taq I, electrophoresed, blotted and hybridised with probes to the HLA-DRB, -DQA, -DQB, DPA and -DPB genes. The restriction endonuclease Msp I was also used with the HLA DPA and -DPB probes. The resulting restriction fragment length polymorphism (RFLP) has been analysed and compared with 55 controls treated in the same way. There was a significant increase in the DRB restriction fragments associated with HLA-DR3 (Fisher's p = 0.011), in particular with a sub-division of DR3 (Fisher's p = 0.0038). These results confirm at the DNA level serological correlations observed for IMN. A 4.5 Kb DQA RFLP was significantly raised in IMN patients (Fisher's p = 0.002) and is proposed as a major disease susceptibility factor. PMID- 2576475 TI - Lack of informative HLA restriction fragment length polymorphisms in autoimmune chronic active hepatitis. AB - Autoimmune chronic active hepatitis (CAH) is strongly associated with HLA-B8, DR3. Accordingly, DNA was isolated from 10 HLA-B8, DR3 control subjects and 11 patients with autoimmune CAH and analyzed for informative restriction fragment length polymorphisms using HLA-DQ beta and DR beta probes, and six enzymes, Hinc II, Bgl II, Bam HI, Rsa I, Taq I and Msp I. None of the polymorphic fragments demonstrable was discriminatory for autoimmune CAH. A genetic polymorphism in the HLA-B8, DR3 region predisposing to autoimmune CAH may not have been detecting owing to an insufficient number of probes or enzymes used, or alternatively HLA DR3 is predisposing by an effect on immune regulation or suppression. PMID- 2576476 TI - Association of RFLP of HLA class I genes with Chinese ankylosing spondylitis patients. AB - By serum typing, it is indicated that HLA B27 may be associated with the susceptibility to ankylosing spondylitis (AS). We analyzed DNA restriction fragment length polymorphism (RFLP) in 28 Chinese AS patients and 99 healthy controls, using a 1.4 Kb HLA class I cDNA probe. The results showed that the frequencies of the 8.1 Kb EcoRI, 5.2 Kb EcoRI and 21.9 Kb XbaI fragments were found to be significantly increased in affected patients (P less than 0.0001, P = 0.0015, respectively), but that of 19.2 Kb XbaI fragment was decreased (P = 0.0021). The data suggest that AS may be a polygenic disease; furthermore, B27 and 8.1 Kb EcoRI band may be two different factors responsible for the susceptibility or just in linkage disequilibrium with the susceptible gene(s). PMID- 2576477 TI - A simple and rapid method for HLA-DQA1 genotyping by digestion of PCR-amplified DNA with allele specific restriction endonucleases. AB - The second exon of the HLA-DQA1 genes was selectively amplified from genomic DNAs of 72 HLA-homozygous B cell lines by the polymerase chain reaction (PCR). Amplified DNAs were digested with HaeIII, Ddel, ScrFI, FokI and RsaI, which recognize allelic sequence variations in the polymorphic segments of the DQA1 second exon, and then subjected to electrophoresis in polyacrylamide gels. Eight different polymorphic patterns of restriction fragments were obtained, and seven were identical to patterns predicted from the known DNA sequences, correlating with each HLA-DQw type defined by serological typing. The remaining one pattern cannot be explained from the sequence data, suggesting the presence of a novel DQA1 allele at the nucleotide level. This PCR-RFLP method provides a simple and rapid technique for accurate definition of the HLA-DQ types at the nucleotide level, eliminating the need for radioisotope as well as allele specific oligonucleotide probes and can be extended and applied to HLA-DR, -Dw DP typing. PMID- 2576478 TI - Molecular analysis of HLA-D region genes in seropositive rheumatoid arthritis. AB - Analysis of HLA DRB1 and DQB1 Bam HI RFLPs revealed four DRB1 (4.8, 5.2, 6.0 and 7.0 kb) fragments and a 3.2 kb DQB1 fragment to be significantly increased in Caucasians with seropositive RA compared to healthy individuals. The 4.8, 5.2 and 7.0 kb DRB1 fragments were found in 86.5% of RA patients and in 56% of the controls (p = 10(-3), relative risk (RR) = 5.0), while the 6.0 kb fragment was found in 79% of RA patients compared to 32% of controls (p = 2 x 10(-5), RR = 8.0). The 3.2 kb DQB1 fragment was observed in 63.5% of RA patients versus 38.0% of controls (p = 10(-2), RR = 2.8). Analysis of these fragments relative to HLA phenotypes revealed that the 4.8, 5.2 and 7.0 kb DRB1 fragments were strongly correlated with DR4, -7, -9 and -w53 serotypes, the 6.0 kb RFLP with DR4 and the 3.2 kb DQB1 fragment with DR1 and DQw1. Using probes specific for the 5' or 3' regions of the DRB1 gene, the 5.2 and 6.0 kb DRB RFLPs were mapped to the 5' end and the 4.8 and 7.0 kb RFLPs to the 3' end of the DRB1 gene. A probe generated from the second exon of the DRB4 (DRw53) gene recognized only the 5.2 and the 6.0 kb RFLPs corroborating the 5' location of these RFLPs. Family studies further confirmed that these RFLP's segregated with HLA phenotypes. PMID- 2576479 TI - Trilateral retinoblastoma in transgenic mice. PMID- 2576481 TI - [A case of Kussmaul-Meier disease]. PMID- 2576482 TI - [The relation of disorders of the blood acid-base equilibrium to immunologic and neurohumoral changes in patients with eczema]. AB - A study of patients with real and microbial eczema showed a direct relation between blood pH, partial pressure, oxygen saturation of the blood and excess of bases and an inverse relation between these values and partial pressure of blood carbon dioxide. A marked inverse relationship was found between the concentration of histamine, serotonin, immunoglobulin G, local autohemolysis and extension of the eczematous process on the one hand and blood pH, partial pressure of oxygen, blood oxygen saturation, excess of bases on the other. The revealed changes give the possibility to design an assumed scheme of development of the eczematous process. PMID- 2576480 TI - Mapping the gene for X-linked cataracts and microcornea with facial, dental, and skeletal features to Xp22: an appraisal of the Nance-Horan syndrome. PMID- 2576484 TI - [Rest position of the eyes and its effect on viewing distance and visual fatigue in computer display work]. AB - A deviation between the angle of convergence during visual work and the resting level of the vergence system (vergence discrepancy) should be associated with costs; subjects should tend to reduce these costs by increasing the observation distance. The remaining costs should contribute to visual fatigue. Both hypotheses were tested using a sample of 40 subjects, mainly students. In agreement with the first hypothesis, subjects with large initial vergence discrepancy increased their observation distance more in the course of 1 1/2 hours of visual work than subjects with smaller initial vergence discrepancy. Visual fatigue was assessed using a set of questions developed in two pilot studies. Contrary to the second hypothesis, visual fatigue did not depend on effective vergence discrepancy, that is, the deviation between the resting level of the vergence system and the actual angle of convergence. In addition, such a relationship was not found for further dependent variables (performance, BMS questionnaire, critical flicker frequency, evaluation of conditions of work, postural complaints). The results are discussed with respect to the role of tonic and dynamic components of the vergence system for visual fatigue. PMID- 2576483 TI - [Pathologic changes in selected laboratory parameters in patients with delirium tremens]. PMID- 2576485 TI - Reserve capacity of the elderly in aging sensitive tests of fluid intelligence: a reanalysis via a structural equation modelling approach. AB - In the last decade there has been a growing interest among developmental psychologists to investigate whether the cognitive performance of older adults can be improved by means of training programs. A number of cognitive training studies involving aging sensitive abilities of fluid intelligence have been performed with healthy older adults (Willis et al. 1981; Baltes et al., 1984/1986). In this paper we reanalyse data from Baltes et al. (1986) concerning the ADEPT Induction, ADEPT Figural Relations, Induction Standard and the Raven's Advanced Progressive Matrices Tests. In contrast to the above study, where the data analysis was based on a MANOVA approach, usually carried out when experimental data were gathered, this discussion implements an approach to change measurement for which the structural equation of different aspects of change in means as manifested in the moment matrices. The results here confirm these by Baltes et al. (1986), and suggest conclusions concerning change in means over time in the experimental and control groups, which are not implied by their study. PMID- 2576486 TI - [Possibilities of objective assessment of the course of activation in ideomotor training]. AB - An active exploration of movement tasks is accompanied with central nervous activation. Its systematical examination needs a teamwork of scientists of various branches of knowledge (i.e. physiology, psychology, sport sciences). Mental training (motor imagination - MI) was chosen as a model for such examinations. In connection with the execution of MI there are characteristic chances of the mean alpha frequency of the EEG, heart rate, respiration rate and skin conductance. The time course of these parameters depends on the number, the duration and the sequence of MI. A graduated submaximal load on ergometer has no influence on the course of the examined parameters. Our investigation allows the conclusion that different activation processes go on within different subsystems during the execution of MI. From a physiological point of view it seems to be necessary that a concrete paradigm of MI must be examined concerning the course of the parameters and, thus, to guarantee the effort of MI. PMID- 2576487 TI - [Analysis of consonant substitutions by dysarthria patients and Spanish speaking Broca's aphasia patients of the La Plata area]. AB - The speech behaviour of 11 patients with exclusively or almost exclusively phonological disorders (2 anarthical patients and 9 with aphasis of the Broca type) is being tested with an one word repetition procedure. This paper only demonstrates the analysis of the consonant substitutions and of the consonant variables under the impact of substitution. The results can be summarized as follows: 1. There is a negative correlation between the amount with which consonant phonemes are substituted and the amount of their use in normal subjects. 2. The group of phonemes which is acquired latest in speech development of the child is also influenced mostly by substitutions. 3. In the majority of substitutions we find a differentiation in one or more variables of the substituent and the substitute. 4. The variables which are influenced by substitutions show an internal hierarchy in the system of language. PMID- 2576489 TI - [Post-infarction stenocardia: comparative evaluation of the results of surgical and conservative treatment]. PMID- 2576488 TI - [Endovascular laser methods in the treatment of arteriosclerotic cardiovascular diseases]. AB - Employment of laser for restoration of adequate blood flow in atherosclerotic vessels is a radically new approach to treatment of cardiovascular diseases of atherosclerotic genesis. Since 1983, wide-scale experimental work has been done at A.N. Bakulev Institute of Cardiovascular Surgery, USSR Academy of Medical Sciences, which has formed the basis for transluminal laser angioplasty (vascular recanalisation with high-intensity laser beam), laser atherolysis (regression of atherosclerotic formations under low-intensity laser beam), and their combinations. Clinical application of these procedures was started in 1985. Sixty two patients with ischaemic heart disease, Takayasu's and Leriche's syndromes, chronic occlusion of pelvic and lower-limb arteries, and with combined lesions of the arterial bed were exposed to targeted transluminal laser. Laser endovascular therapy alone and in combination with balloon angioplasty or bypass surgery was used. Application of these methods showed their high efficacy. Successful recanalisation and restoration of adequate flow (confirmed by Doppler echography and angiography) were achieved in 93 per cent cases; results were poor (no effect, complications) in 7 per cent cases. PMID- 2576491 TI - [Biologic validation of nosologic constructs]. PMID- 2576492 TI - Drugs recently released in Belgium. Recombinant human erythropoietin--nizatidine. PMID- 2576490 TI - [The role of neurochemical mechanisms of the dorsal raphe nucleus in various models of anxiety states in rats]. AB - Dopamine and serotonin microinjection in the dorsal raphe nucleus of rats does not influence the alarm state in the test of "threatening situation" avoidance, but increases or weakens the state of alarm in the rest of "illuminated site" avoidance. Local injection of GABA in this midbrain formation weakens the alarm state in the test of "threatening situation" avoidance but is not effective in the test of "illuminated site" avoidance. Chemical stimulation of the raphe nucleus by glutaminic acid does not influence the two different experimentally modelled states of alarm, but modulates the mechanisms controlling the instinct of darkness preference by rats. PMID- 2576494 TI - Molecular genetic approach to the analysis of clonal proliferation in hematologic disorders. AB - The clonal composition of each cell population was determined from the characteristic methylation pattern of DNA and the restriction fragment length polymorphism (RFLP) of the hypoxanthine phosphoribosyltransferase (HPRT) and phosphoglycerate kinase (PGK) genes, both located on the X chromosome. About 71% of Japanese females are heterozygous in terms of the RFLP of either HPRT or PGK genes, which was demonstrated by using 5' genomic DNA or cDNA probes for these genes. All 3 cases of chronic myeloproliferative disorders showed monoclonal patterns. AML or ALL cases demonstrated either monoclonal or polyclonal patterns depending upon the percentage of blastic cells. Monoclonal patterns were seen in 3 of 4 cases of myelodysplastic syndromes and both PNH cases. PMID- 2576493 TI - Insulin secretion induced by alloantigens. Mechanisms of action. AB - Basal insulin secretion stimulated by allogeneic lymphocyte injection was inhibited by SRIF, diazoxide and verapamil but was not affected by theophylline or imidazole. Glucose stimulated insulin secretion induced by alloantigens was inhibited by imidazole. Maximum insulin secretion was achieved with 2.1 mg/ml theophylline in allogeneized mouse pancreata and with 4.2 mg/ml in control pancreata. Propranolol also blocked allogen-induced glucose-stimulated insulin secretion. Phentolamine enhanced insulin secretion from both experimental groups, but phentolamine plus epinephrine only stimulated insulin secretion in control pancreata. Verapamil, diazoxide and SRIF diminished insulin secretion in both experimental groups. These results suggest that: a) basal insulin secretion induced by alloantigens may be mediated by an increase in calcium translocation, and b) glucose-stimulated insulin secretion induced by alloantigen may be mediated by a rise in B-cell cAMP. PMID- 2576495 TI - [Modifications in neurotransmission in degenerative dementia]. PMID- 2576496 TI - [Biochemical and molecular study of amyloid protein A4 deposited in senile plaques]. PMID- 2576498 TI - [Effects of neurotransmitters and blockers on electroretinogram c-wave and light peak of the chick]. AB - Effects of neurotransmitters (GABA, glycine) and their antagonists (picrotoxin, strychnine) on retinal potentials were investigated in the chick. Electroretinogram (ERG) c-wave and light peak of the standing potential of the retina were recorded from the eyes of anesthetized chicks by a standard method of direct current recording after intravitreal injection of various concentrations of GABA, glycine, picrotoxin and/or strychnine. The amplitude of the c-wave was measured at 2 and 5 sec after onset of the light stimulus, using as indices the fast-rise c-wave (cF-wave) and the slow-rise c-wave (cs-wave), respectively. GABA (10(-6)M) and glycine (10(-5)M) enhanced the amplitude of the c-wave but maintained normal waveform. Picrotoxin (3mM) reversed the polarity of the cs-wave from positive to negative, whereas the cF-wave maintained normal polarity. An injection of strychnine (10mM) alone depressed the c-wave amplitude but did not change the waveform. The amplitude of the light peak of the retinal standing potential increased by administration of GABA or glycine, whereas it decreased with picrotoxin or strychnine. Post d-trough and post d-peak were enlarged by picrotoxin, while they were suppressed by strychnine. The results suggest that GABA and glycine are possibly related to generation of the c-wave and the light peak. PMID- 2576497 TI - The 3' untranslated region of the A4 amyloid mRNA stimulates the translation. PMID- 2576499 TI - [Alpha-adrenoblockers and adrenoreceptor function in obstetrical pathology]. PMID- 2576500 TI - [Neuromediators and memory. From research to therapy]. PMID- 2576501 TI - [Efficacy of long-acting somatostatin in refractory diarrhea in 2 patients with AIDS]. PMID- 2576502 TI - Evidence for increased calcium buffering in motor-nerve terminals of aged rats. PMID- 2576504 TI - The discovery of new chemical modulators of the N-methyl-D-aspartate receptor. PMID- 2576503 TI - Neuronal Ca2+ channels and their regulation by excitatory amino acids. PMID- 2576505 TI - Glutamate neurotoxicity, calcium, and zinc. PMID- 2576506 TI - Neurotoxicity at the N-methyl-D-aspartate receptor in energy-compromised neurons. An hypothesis for cell death in aging and disease. AB - Our results demonstrated that the neurotoxicity of glutamate and closely related agonists was mediated by the NMDA receptor in rat cerebellar granule cells. Evidence was presented to support our hypothesis that the pivotal event in the transition of these EAAs from neurotransmitters to neurotoxins is relief of the voltage-dependent Mg++ block of the NMDA channel due to changes in membrane potential which can be caused by depletion of highly phosphorylated nucleotides or by other depolarizing stimuli. Persistent stimulation of NMDA receptors whose channels are unblocked by Mg++ can permit excessive influx of Na+ and Ca++ and neuronal death can follow by a mechanism not yet understood. Glutamate is not toxic at kainate receptors although they are present on these cells. These findings underline the potential importance of perturbations in energy metabolism in a variety of neurodegenerative disorders and in the normal process of aging which share the common feature of the loss of neurons. PMID- 2576507 TI - Calcium, excitotoxins, and neuronal death in the brain. PMID- 2576508 TI - Calcium-induced neuronal degeneration: a normal growth cone regulating signal gone awry (?). AB - The neuronal growth cone is involved in neurite elongation, directional pathfinding, and target recognition. These activities are essential for proper assembly of functional circuits within the developing nervous system, for regeneration of functional circuitry following damage, and also, perhaps, for remodeling of the nervous system in response to environmental stimuli. Our studies of both molluscan and mammalian neurons in culture have shown that neurite outgrowth can only proceed when intracellular calcium levels lie within a specific outgrowth-permissive range. Cessation of outgrowth can be induced by a variety of signals normally used for communication within the adult nervous system, including neurotransmitters, and action potentials; all of these signals elevate levels of intracellular calcium above the outgrowth-permissive range. For example, glutamate, whether added to the medium or released from co-cultured entorhinal explants, can selectively inhibit dendritic outgrowth. Conversely, inhibitory neurotransmitters can block the outgrowth-inhibitory effects of glutamate and actually promote expansion of dendritic arbors. Dendritic outgrowth is therefore regulated by a balance between excitatory and inhibitory neurotransmitter activity. Extreme excitatory imbalance in neurotransmitter input to pyramidal neurons causes cell death. Each of these changes in neuroarchitecture is mediated by changes in levels of intracellular calcium. We therefore put forward the hypothesis that key mechanisms which normally control the development and plasticity of neural circuitry, are also involved in neurodegeneration. Local, moderate elevations in calcium result in dendritic pruning. Higher, global elevations in calcium result in cell death. This cell death may serve an important function during normal development; aging may result in the same mechanism being employed pathologically. When intracellular calcium levels are not regulated within normal limits, as may occur in aging, neurodegeneration may occur. PMID- 2576509 TI - Regulation of calcium in isolated nerve terminals (synaptosomes): relationship to neurotransmitter release. PMID- 2576510 TI - Possible involvement of free radicals in neuroleptic-induced movement disorders. Evidence from treatment of tardive dyskinesia with vitamin E. PMID- 2576511 TI - [A century of dermatology. The history of the French Society of Dermatology and Syphiligraphy]. PMID- 2576512 TI - [Neonatal erythroderma. Conceptual development over 100 years: from 1889 to 1989]. PMID- 2576513 TI - [Acquired bullous diseases. Development of idea over a century. Congress of 1889]. PMID- 2576514 TI - [Trichophyton: a century of progress]. PMID- 2576515 TI - [22 June 1889. The founding of the French Society of Dermatology and Syphiligraphy]. PMID- 2576516 TI - [Interaction of rilmenidine with renal imidazoline-guanidine sites]. AB - Several studies have suggested that clonidine, guanfacine and rilmenidine decrease systemic blood pressure by stimulating central alpha 2-adrenergic receptors. However, we have shown that these molecules interact not only with alpha 2-adrenergic but also a new type of "non catecholamine" receptor in rabbit and human renal proximal tubules. This receptor, which we have called the imidazoline-guanidium receptor site (IGRS) seems to be pharmacologically, biochemically and fractionally distinct from alpha 2-adrenergic receptors. In order to determine the relative affinity of rilmenidine for these two types of receptor, we studied its capacity to inhibit the liaison of (H3)-idazoxan, a ligand with a high affinity for the IGRS, and of (H3)-rauwolscine, a ligand selective for alpha 2-adrenergic receptors in the rabbit kidney. The results based on the apparent constants of inhibition (Ki) of the two radioligands [231 +/- 34 nM for (H3)-idazoxan and 2440 +/- 322 nM for (H3)-rauwolscine] showed that the selectivity of rilmenidine was 10 times greater for IGRS than for alpha 2 adrenergic receptors. This preferential activity on IGRS was confirmed by studies of the influx of Na22 into isolated renal proximal tubule cells of the rabbit. They showed that rilmenidine, in contrast to catecholamines, inhibited the transport of Na22 into the renal cells. In conclusion, the data from our studies shows that rilmenidine interacts with renal IGRS and inhibits cellular transport of sodium by a mechanism other than the stimulation of alpha 2-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576517 TI - Neuroendocrine control of blood tonicity and volume. AB - The numerous studies cited in this chapter clearly show that very complex mechanisms are involved in the cardiovascular and osmotic regulation of AVP release. Information from peripheral receptors within the cardiovascular system and from central osmoreceptors is carried by multisynaptic neural inputs to the SON and PVN. This information is co-ordinated at one or more sites within the hypothalamus, the brain stem, or even the neurohypophysis itself, to ensure release of the appropriate amount of AVP. In many cases the origin of the pathway and the nature of the neurotransmitter is known, but further studies are needed to establish their physiological role in AVP release. PMID- 2576518 TI - [The (15N) ammonium test in clinical research]. AB - By use of the [15N]-ammoniumtest the liver function is investigated under influence of hormonal contraceptives in women and in liver diseases in children. With the described noninvasive nonradioactive isotope test the ammonia detoxification capability and the urea synthesis capacity of the liver is determined by measuring of the 15N-exceretion in ammonia and urea in the urine after oral administering of [15N]-ammonium chloride. The [15N]-ammonium test shows a significant influence of the hormonal contraceptives on the liver function and gives diagnostic evidence for liver diseases in children. PMID- 2576519 TI - Posttranscriptional control of human homeobox gene expression in induced NTERA-2 embryonal carcinoma cells. AB - We have studied the expression of four human homeobox genes representative of four different clusters (i.e., HOX-1, HOX-2, HOX-3 and HOX-5) in the embryonal carcinoma (EC) cell line NT2/D1. Following treatment with retinoic acid (RA), these cells differentiate into several cell types, including neurons, and steadily accumulate polyadenylated transcripts derived from the genes in a period ranging from 18 hr to 14 days of RA treatment. The sizes of major transcripts in differentiated EC cells coincide with those previously detected by the same probes in human embryos. Nuclear run-on transcriptional analysis showed no difference in the transcription rate of the four homeobox genes in differentiated vs. undifferentiated EC cells. Inhibition of protein synthesis by 5-18 hr of treatment of undifferentiated cells with cycloeximide causes accumulation of some homeobox transcripts at levels comparable to those observed after 18 hr of RA induction, although it does not cause superinduction in fully differentiated cells. These data suggest that the activation of homeobox gene expression in RA induced EC cells is controlled, at least in part, by posttranscriptional mechanisms. PMID- 2576520 TI - BstEII restriction fragment alleles and haplotypes of the human IGHG genes with reference to the BamHI/SacI RFLPs and to the Gm polymorphism. AB - In previous studies, we have described, for each of the five human immunoglobulin IGHG (C gamma) genes, BamHI, SacI and BamHI/SacI allelic restriction fragments. Further, we have determined BS (BamHI/SacI) linkage groups of alleles for the whole of the IGHG loci and we have demonstrated correlation with the Gm alleles and haplotypes. In this paper we characterize more precisely the polymorphism of the IGHG genes and, consequently, the structure and evolution of this multigene family, using the restriction enzyme BstEII and two different probes, a IGHG (C gamma) probe and a G3 (C gamma 3) specific probe. Alleles and haplotypes of the BstEII restriction fragments have been defined with reference to the BS alleles and haplotypes. New RFLPs of the IGHG genes are described and unambiguous correlations have been established with most of the Gm alleles and haplotypes. Thus, the IGHG gene RFLPs strengthen the Gm polymorphisms as powerful tools for the characterization of populations, disease and genetic marker linkage analyses, forensic medicine and evolution of these IGHG genes. PMID- 2576521 TI - A family with an apparent HLA-DR triplet: evidence for exchange of functional HLA DR beta-genes between different haplotypes. AB - Serological and protein analysis showed that HLA-DR1 and DR2 short (s) segregated together as one haplotype, resulting in a HLA-DR triplet as found in a family study. Both DR1 and DR2 molecules were coordinately expressed and were shown to function as restriction elements in antigen presentation assays. This unique HLA DR1, 2s haplotype was further studied by Southern blot analysis. Based upon well known restriction fragment length polymorphisms for the involved gene sets, i.e. DR1 and DR2 along with the DR type from the other haplotype, the genes as identified by restriction fragment length polymorphism of the triplet could be established. Pseudogenes, which are included in the previously described gene sets of HLA-DR1 and DR2 are apparently lacking in the triplet. We therefore postulate that during an unequal crossing-over event the DR beta-pseudogene of DR2 could be exchanged by a functional DR1 beta-gene. PMID- 2576522 TI - Oral vaccination of rats with live avirulent Salmonella derivatives expressing adhesive fimbrial antigens of uropathogenic Escherichia coli. AB - The avirulent Salmonella typhimurium F885 was transformed with a plasmid carrying the cloned S fimbriae genes of a uropathogenic Escherichia coli. The resulting transformant (F885-1) produced efficiently E. coli S fimbriae and was used for live oral vaccination of rats. For comparison rats were immunized subcutaneously with isolated S fimbriae. Both routes of vaccination resulted in a significant IgG antibody response to S fimbriae. In addition live oral vaccination induced a serum IgA response against S fimbriae. After transurethral infection of rats with a S fimbriae producing E. coli a 10-fold reduction of bacterial counts in the kidney was observed in rats orally vaccinated with F885-1 as compared to unvaccinated controls. This study suggests that the avirulent Salmonella F885 may be used as a fimbrial antigen carrier for oral vaccination against renal infections. PMID- 2576523 TI - DNA analysis of histocompatibility antigens of a sample of the Sao Paulo population. AB - 1. Human major histocompatibility complex (HLA) antigens have attracted great interest because of their prominent role in cell-mediated immune response and thus in graft rejection. An enormous variety of histocompatibility antigens has been demonstrated and the number of known antigens increases every year. 2. The objective of the present study was to apply restriction fragment length polymorphism (RFLP) analysis to the normal population of Sao Paulo in order to confirm and extend the scope of our laboratory's cell panel for HLA typing. 3. DNA typing of class I antigens has not been very productive since only some specificities correlate with DNA fragments demonstrable with Southern blots. In contrast, DNA typing of class II antigens is a valuable tool for reclassifying cells previously typed by anti-HLA sera. Since antisera for recently described HLA antigens are not easily available, the development of a well-characterized panel is essential for the correct screening of incoming sera. These sera, in turn, permit the accurate typing of donor-recipient pairs in kidney and bone marrow transplantation. PMID- 2576524 TI - On the mechanism which mediates the effects of long-term administration of fencamfamine in rats. AB - This study analyzes the changes in the sensitivity of striatal dopaminergic (DA) receptors to apomorphine following withdrawal from long-term treatment with fencamfamine (10 mg/kg, for 40 days). Fencamfamine treatment decreased (34.8 +/- 3.2 vs 25.8 +/- 2.8, P less than 0.05) the stereotyped behavior induced by apomorphine (2.0 mg/kg, sc), but potentiated the effect of apomorphine (0.02 mg/kg, sc) in reducing the striatal levels of homovanillic acid (HVA) (0.41 +/- 0.02 micrograms/g vs 0.31 +/- 0.03 micrograms/g, P less than 0.01) and dihydroxyphenylacetic acid (DOPAC) (0.45 +/- 0.04 micrograms/g vs 0.34 +/- 0.03 micrograms/g, P less than 0.01). These results suggest that changes in pre- or postsynaptic DA receptors may underlie the tolerance and sensitization to the effects of fencamfamine. PMID- 2576525 TI - Human buccal epithelial cell receptors of Pseudomonas aeruginosa: identification of glycoproteins with pilus binding activity. AB - Adherence of Pseudomonas aeruginosa to a patient's epithelial surface is thought to be an important first step in the infection process. Pseudomonas aeruginosa is capable of attaching to epithelial cells via its pili, yet little is known about the epithelial receptors of this adhesin. Using nitrocellulose replicas of polyacrylamide gels of solubilized human buccal epithelial cells (BECs), glycoproteins (Mz: 82,000, and four bands between 40,000 and 50,000) that bound purified pili from P. aeruginosa strain K (PAK) were identified by immunoblotting with a pilus-specific monoclonal antibody that does not affect pilus binding to BECs (PK3B). All pilus-binding glycoproteins were surface localized, as determined by surface radioiodination of intact BECs. Binding of pili to all of the glycoproteins was inhibited by Fab fragments of monoclonal antibody PK99H, which inhibits PAK pili binding to BECs by binding to or near the binding domain of the pilus, but not by Fab fragments of monoclonal antibody PK41C, which binds to PAK pilin but does not inhibit pili binding to BECs, demonstrating that pilus binding to these glycoproteins is likely via the same region of the pilus that binds to intact BECs. Periodate oxidation of the blot eliminated pili binding to all glycoproteins, indicating that a carbohydrate moiety is an important determinant for pilus-binding activity. However, not all of the glycoproteins exhibited the same degree of sensitivity to periodate oxidation. Furthermore, monosaccharide inhibition of pilus binding to BECs implicated L-fucose and N acetylneuraminic acid as receptor moieties. PMID- 2576526 TI - Interaction of amineptine with agents modifying dopaminergic transmission. AB - Amineptine, administered at increasing doses (5-40 mg/kg, i.p.) in mice, induces a dose-dependent hyperactivity (measured either in classical activity cages or in a DIGISCAN actimeter) which persists for about 8 h at 20 mg/kg. The increase of locomotor activity induced by 20 mg/kg amineptine is dose-dependently antagonized by metoclopramide (1.25-120 mg/kg i.p.), by SCH 23390 (7.5-8,000 micrograms/kg s.c.) and by amisulpride (1.56-50 mg/kg i.p.). Nevertheless, whereas the increase of locomotor activity induced by amineptine is completely antagonized at a relatively low dose of the discriminant benzamide derivative amisulpride (50 mg/kg i.p.), it is completely antagonized only at high doses of the selective D-2 antagonist metoclopramide (80 mg/kg i.p.) and of the selective D-1 antagonist SCH 23390 (4,000 micrograms/kg s.c.). The increase in locomotor activity induced by amineptine is significantly reduced (a) by low doses of apomorphine (25-300 micrograms/kg s.c.) stimulating dopamine autoreceptors; (b) by a pretreatment with reserpine (4 mg/kg s.c. 24 h prior to testing), which depletes the vesicular stores of monoamines; and (c) by gammabutyrolactone (100 mg/kg i.p. 30 min after amineptine), which inhibits the firing rate of dopaminergic neurons. Similar results are also obtained with the selective dopamine uptake inhibitor GBR 12783 (10 mg/kg i.p.) but not with dexamphetamine (5 mg/kg i.p.), the effects of which persist in reserpine-pretreated mice in gamma-butyrolactone-treated mice. Finally, the study of the interaction of increasing doses of amineptine with dexamphetamine (5 mg/kg i.p.) indicates that a low dose of amineptine (5 mg/kg) potentiates dexamphetamine-induced hyperactivity, whereas a high dose of amineptine (40 mg/kg) reduces dexamphetamine-induced hyperactivity. These data indicate that the stimulation of dopamine receptors induced by amineptine depends to a large degree on the dopamine released from the vesicular stores by the firing rate of dopaminergic neurons. The similarity of the results obtained with amineptine and with the selective dopamine uptake inhibitor GBR 12783 suggests a common mechanism of action that differs from that of dexamphetamine. PMID- 2576527 TI - [Pathogenesis of Parkinson's disease, a molecular genetic approach]. AB - In juvenile parkinsonism (JP), unlike naturally occurring Parkinson's disease, high frequency of familial onset is observed, which suggests the involvement of some genetic factor(s) in the pathogenesis of the disease. In an attempt to conduct a molecular genetic approach to JP, we tried to isolate tyrosine hydroxylase (TH) cDNA from human pheochromocytoma, and demonstrated the existence of four types of cDNA (type 1, 2, 3 and 4), differing in the 5'-terminal region. All four cDNAs had the same sequence in common from ATG of the translation start codon to 90th nucleotide. However, in types 2, 3 and 4, characteristic sequences were inserted between 90th and 91 st nucleotides of type 1 cDNA. TH genomic DNA cloning showed that the multiple form of mRNA were produced from a single gene through alternative splicing. Four types of cDNA was expressed in COS cells. They exhibited different homospecific activities: type 1 TH having the highest activity, others less than 40% of type 1 TH. The question whether possible change in TH gene is related to the pathogenesis of JP is now being pursued based on these molecular biological understanding of TH gene. PMID- 2576528 TI - [Neuronal degeneration and glutamate]. AB - Pathological conditions which interfere with normal brain energy metabolism causes similar neuronal degeneration. Cerebral ischemia, hypoglycemia, and status epilepticus are well known examples of such disease processes. Recently, it has come to be realized that the similarity of the pattern of neuronal degeneration is probably due to the toxicity of a putative neurotransmitter glutamate. Ischemic hippocampal damage in rodents has been studied as a typical experimental model. Following brief ischemia, the rodent hippocampus recovers completely and then starts degenerating over a few days. The delayed neuronal death of the hippocampus could be accounted for by excitotoxic action of glutamate. There is a considerable body of evidence to support this hypothesis. Extracellular glutamate actually increases following brief ischemia. Preceding destruction of glutamatergic input to the hippocampal CA1 (deafferentation) partially prevents ischemic neuronal damage in CA1. Various drugs are reportedly effective in preventing ischemic CA1 damage and some of them have a property of glutamate antagonist. However, why glutamate brings about cell necrosis is still not fully understood. Further study of basic mechanism is awaited. PMID- 2576530 TI - An overview of nephrology in China. PMID- 2576529 TI - Sigje, a member of the small inducible gene family that includes platelet factor 4 and melanoma growth stimulatory activity, is on mouse chromosome 11. AB - Stiles and coworkers originally identified a gene they termed JE that is transcriptionally activated in mouse fibroblasts early after treatment with platelet derived growth factor or serum. This gene, now named Sigje, can encode a 148-amino acid secreted, basic polypeptide that belongs to the small inducible gene (SIG) family whose members include, for example, platelet factor 4, melanoma growth stimulatory activity (Mgsa), and interferon inducible protein 10. SIG family members share a conserved array of cysteine and proline residues and a similar predicted secondary structure, and may have evolved from a common ancestral gene. Several members of the SIG family have been assigned to the proximal long arm of human chromosome 4, to a region that has genetic homoeology with a portion of mouse Chromosome 5. We report here that mouse Sigje, in contrast to Mgsa, is on Chromosome 11. Sigje restriction fragment length polymorphisms in Mus spretus DNA were identified with the enzymes TaqI, MspI, BclI, and XbaI, and will be useful in mapping by meiotic recombination. PMID- 2576531 TI - Thresholds for the physiologic effects of adrenergic agents: a methodologic appraisal. AB - For hemodynamic responses to adrenergic agents, classical pharmacodynamic theory describes differences between agents in receptor specificity, potency and pharmacologic profile from derived parameters such as the ED50 or half-maximal concentration. However, pharmacodynamic parameters are derived exclusively from in vitro studies. We describe a method of analysis which permits derivation of the 'threshold' or minimum plasma drug concentration associated with discernible effects. The threshold is derived by graphic analysis of in vivo dose response data. We provide examples of both animal and human data which demonstrate agreement of experimental results with predicted responses. This approach permits more direct comparison of studies from different investigators, from different patient or diagnostic categories or at different developmental ages. PMID- 2576532 TI - Liver gamma-glutamyl transpeptidase activity following chronic treatment with acetylsalicylic acid in rats. AB - In the present study, rats were administered acetylsalicylic acid (ASA), at low and high doses, by means of a gastric tube for 30 days. Chronic administration of a high dose of ASA (200 mg/kg body weight) resulted in a significant increase in liver plasma membrane gamma-glutamyl transpeptidase activity, cholesterol, and phospholipid levels. The enzymatic activity and lipid levels appeared not to be affected by ASA when given at a lower dose (50 mg/kg body weight). The changes in the enzymatic activity of plasma membrane were positively correlated to membrane cholesterol content. These findings suggest that the hepatotoxicity of high doses of ASA should not be overlooked during clinical use of the drug. PMID- 2576533 TI - Prenatal diagnosis of cystic fibrosis. Analytical evaluation of microvillar enzyme determinations in amniotic fluid. AB - The activity of gamma-glutamyltranspeptidase and total alkaline phosphatase and its isoenzymes has been determined in 261 amniotic fluid samples taken from pregnant women with known normal outcome and in 30 amniotic fluid samples from pregnant women with a 1:4 risk for cystic fibrosis (CF). Preliminarily, 114 amniotic fluid samples were assayed in parallel in three different laboratories, and a good correlation was found even though different assays were used. From the results obtained in control amniotic fluids, normal range and CF-predictive cutoff values were established. No false-negative results were found in this study. Among the predicted affected pregnancies 7 were terminated, and 3 went to term: 1 resulting in a CF-affected child and the other 2 in healthy children. CF was confirmed in all the aborted fetuses. In 1 case the results were inconclusive. In this study numerical results obtained for samples with a 1:4 risk of CF analyzed in the three laboratories were always virtually identical. PMID- 2576534 TI - Different effects of ANP and nitroprusside on cyclic GMP extrusion of isolated aorta. AB - Atrial natriuretic peptide (ANP) and sodium nitroprusside have potent vasodilator effects on the noradrenaline-precontracted isolated rabbit aorta. A distinct elevation of cyclic GMP in the aortic tissue was observed after both vasodilators. In contrast to sodium nitroprusside, ANP-(5-28) induced a dose dependent cyclic GMP extrusion from the tissue into the medium. Thus, release of cyclic GMP appears to be specific for activation of particulate guanylate cyclase and provides a mechanism in addition to synthesis and degradation by which the cells can regulate their internal concentrations of cyclic GMP. PMID- 2576535 TI - In vitro secretion of hormones from the islets of pancreas with acinar atrophy- influence of digestion with collagenase. AB - The release of insulin, glucagon and somatostatin from islets isolated by microdissection, and islets isolated by aid of different duration of collagenase digestion from pancreases with exocrine atrophy was assessed. Prior collagenase digestion caused an increased release of insulin and glucagon, but not somatostatin; also, the non-suppressibility of glucagon secretion despite high glucose concentration in the medium was characteristic for those islets. Additional data suggest that in the absence of intrinsic pancreatic proteases the nature of the damage conferred by collagenase to islet B- and A-cells is different. In the light of action of epinephrine, an inhibitor of insulin secretion, possible mechanisms responsible for disturbed hormone release in the presence of proteolytic enzymes are discussed. PMID- 2576536 TI - Evaluation of ophthalmoscopy by nonophthalmologists in diagnosing chronic glaucoma in West Africa. PMID- 2576538 TI - Amniotic fluid prolactin levels in rhesus isoimmunized patients. AB - The concentration of prolactin in the amniotic fluid (AFPRL) was measured in 75 samples obtained in the third trimester of 14 isoimmunized women. There was a uniform decline in prolactin levels with advancing gestation in each pregnancy (r = -0.89 to -0.99). The decline in AFPRL was similar in uncomplicated pregnancies. AFPRL levels were not predictive of umbilical cord hemoglobin or bilirubin levels and amniotic fluid lecithin/sphingomyelin ratio. PMID- 2576537 TI - Pregnancy outcome in unmarried teenage nulligravidae in Singapore. AB - Singapore, like other newly industralized countries, has seen a dramatic transformation in the social standards of its population in a particularly short space of time. Unfortunately, this period of development has been accompanied by an escalation in the number of pregnancies to unmarried teenage girls. This paper examines the obstetric and social implications of 150 such pregnancies in younger and older teenagers. Poor intrauterine growth in the younger teenager appears to be the most important adverse obstetric outcome in that mean birthweight was significantly reduced (2738 g compared to 3054 g; P less than 0.02). We believe this to be an important explanation for the five-fold increase in perinatal mortality seen in this group of mothers. Unlike some other reports, we found no significant increase in the incidence of cephalopelvic disproportion, anemia or pregnancy induced hypertension in these mothers. The social implications of teenage pregnancy in Singapore are also examined and recommendations made for methods to curb the problem. PMID- 2576539 TI - The outcome of labor at the University Teaching Hospital (CHU), Yaounde, Cameroon. AB - The University Teaching Hospital, Yaounde, Cameroon became operational in 1982. This retrospective study analyses the performance of the maternity unit during the first 5 years. Data was obtained from casenotes, annual reports, delivery and operation registers. The maternal mortality rate (MMR) is one of the lowest in Africa. The perinatal mortality is low but could be improved upon. The reasons for the low MMR is discussed. It is possible to reduce the appalling MMRs of developing countries without sophisticated technologies. PMID- 2576540 TI - Biomagnetic measurements of the brain activity of preeclamptic pregnant women using a superconducting quantum interference device. AB - Biomagnetic brain activity was studied in 17 full-term pregnant women with symptoms of pre-eclampsia using the biomagnetometer SQUID. The results show obvious differences both in the waveforms and in the spectra that obtained from statistical Fourier analysis by comparing them with the corresponding results from 87 pregnant women with normal full-term pregnancies. Specifically, in the pathological pregnancies the high magnetic field activity emitted from points of the mother's brain is distributed in the 2-7 Hz band frequency range whereas in normal pregnancies we found low magnetic field activity distributed over the 7 Hz band frequency. PMID- 2576541 TI - A needs assessment study of traditional birth attendants in rural Kenya. AB - For several reasons traditional birth attendants (TBAs) still deliver the majority of women in many developing areas of the world. A needs assessment study of TBAs serving one area of Kenya was conducted for the purpose of designing an appropriate intervention program. Thirty-six TBAs were interviewed. Together, they had attended to a total of 116 deliveries within 1 month. The local hospital was conducting an average of 37 deliveries per month. Although most TBAs were good at abdominal palpation, they did not conduct routine prenatal checks and rarely referred their clients to hospital. Several risky practices were identified from which a training program has been designed. The findings and their implications are discussed within the context of improved MCH/FP services. PMID- 2576542 TI - Breastfeeding and return to ovulation in Bangkok. AB - Twenty-seven breastfeeding mothers and nine non-breastfeeding postpartum comparison mothers in Bangkok, Thailand were followed longitudinally until ovulation resumed. A simple set of guidelines is described involving three obvious milestones for the breastfeeding mother to safely use the natural contraceptive benefit of breastfeeding. Those milestones are the first menses, the initiation of supplementation and the child's monthly birthday. In the absence of menses and supplementation, 93% of breastfeeding mothers remained anovular for 3 months postpartum and 88-89% for up to 6 months. Further, the work of other investigators suggests that the proportion ovulatory provides an overestimate of those at risk of pregnancy. The guidelines suggest a way to estimate the period of lactational infertility and may be most useful on a programmatic level. PMID- 2576543 TI - Mortality in acute gynecology: a developing country perspective. AB - Over a 20-month period 109 deaths were recorded in the Acute Gynecology Ward, Kenyatta National Hospital, Nairobi; a rate of 5 deaths per month. Forty-one percent of the deaths were directly attributable to pregnancy and 46% were due to malignancy (mainly cervical carcinoma). Of the dead, 12.4% were teenagers and 63% below 35 years in age. They were generally of low parity. A tragic picture is presented of death of young women in their prime from almost entirely preventable causes. The need for improved maternal care, including family planning and cytological screening for cervical carcinoma is discussed and emphasized. PMID- 2576544 TI - Endometriosis: incidence among the Igbos of Nigeria. AB - A retrospective study of the incidence of endometriosis among the Igbos was undertaken. The incidence was 4.3% in patients with pelvic operations. This is the highest incidence ever reported for Nigeria. Differences in educational standards, ethnic habits and improved diagnostic resources of this hospital were the possible influencing factors; 90.8% of the cases were not diagnosed before operation, demonstrating the lack of awareness. Differential diagnostic considerations for menstrual disorders should include endometriosis in this environment. PMID- 2576545 TI - Factors relating to the volume of surgical knots. AB - The suture's knot site represents the highest amount and density of foreign body material of a knotted suture loop. The volume of a knot is directly related to the total amount of inflammatory reaction surrounding the knot. We measured the volume of seven surgical knots frequently used in surgical practice. Two different suture materials and two different sizes were tested. Suture size was found to contribute significantly more to the volume of all knots tested than the number of throws of which the knots were composed. Knots made with coated multifilament polyglactin-910 were significantly larger than the knots made with monofilament nylon. Clinical implications of these findings are discussed. Surgical techniques keeping the volume of knots to a possible minimum, are encouraged. PMID- 2576547 TI - Perforated adenocarcinoma of the colon during pregnancy. AB - Performated carcinoma of the colon in pregnant women is a rare event. Only six cases have been reported in the literature, all except one in the recto-sigmoid. We present a case of perforated adenocarcinoma of the colon located above the peritoneal reflection and discuss the problem of diagnosis and management. PMID- 2576548 TI - Recurrent trophoblastic neoplasia. AB - An unusual case of recurrent benign trophoblastic growth occurring for the fourth time in a gravida 4, para 0, 30-year-old woman is reported. Prophylactic chemotherapy was instituted to avert the disaster again, without success. The question of her future obstetric outcome poses a formidable dilemma and no radical measures could be undertaken, as the patient hoped for a normal pregnancy. PMID- 2576549 TI - Malignant degeneration of a mature ovarian teratoma. AB - Malignant components are present in 1-2% of mature teratomas (dermoid cysts) and historically have been associated with a very poor prognosis. Patients with malignant mature cystic teratomas typically are postmenopausal and may present with a rapidly enlarging tumor or systemic symptoms suggestive of malignancy. However, the diagnosis is rarely made pre-operatively and, if the tumor is not metastatic, may not be made until the tumor is examined microscopically. Squamous cell carcinoma is the most common malignancy found in mature cystic teratomas. We present a 26-year-old woman with this cancer in whom the disease proved fatal. A surgical approach to patients with malignant mature teratomas is suggested. Prognostic factors and adjuvant therapy are discussed. PMID- 2576546 TI - Rudimentary horn pregnancy associated with pre-eclampsia. AB - The unusual association of pre-eclampsia with a pregnancy in the rudimentary horn of the uterus in a multigravid patient is reported. The infrequent development of rudimentary horn pregnancy beyond the twentieth week of gestation may explain the rarity of this complication. The possible effect of rapid distension of the rudimentary horn with exposure of the myometrial surface to overwhelming fetal antigenic proteins may be of relevance in the development of pre-eclampsia in this case. PMID- 2576550 TI - Haemophilus influenzae bacteremia following first trimester abortion. AB - While genital tract infections with Haemophilus influenza (H. influenzae) are recognized with increasing frequency, this organism still remains an uncommon cause of maternal infection. The association of this pathogen with spontaneous abortion is extremely rare and has been described only in cases of midtrimester abortion. We report a case of H. influenzae bacteremia following first trimester spontaneous abortion and review the literature. PMID- 2576551 TI - Psychosexual aspects of virilization syndrome. AB - A case is reported of a 35-year-old black woman with marked hirsuitism. The focus is on the psychosexual aspects of her illness. Physicians must attend to the potentially devastating effects of virilization syndrome on their female patients. PMID- 2576552 TI - HIV antibody screening in a gynecology and obstetrics clinic Ankara, Turkey. AB - In 416 pregnant women, admitted to our outpatient obstetric clinic for antenatal care between December 1987 and August 1988, HIV antibody assessments were performed by ELISA technique. No seropositive case was reported. PMID- 2576554 TI - [Dermatotoxicity caused by Chrysaora hysoscella. Presentation of a case]. AB - Chrysaora hysoscella L. rarely occurs in coastal waters of the Adriatic sea and is usually considered an innocuous jellyfish. In June 1989, P.D.N., a 29 year old healthy female, biologist at the Marine Biology Laboratory of Trieste, treated some samples of Chrysaora hysoscella captured that day. She took the animals from the transport tanks and cut the tentacles and oral arms from their bell. About ten minutes later she felt itching and burning of her hands, especially the right one. Twenty minutes later erythematous and slightly edematous lesions appeared on her fingers. These lesions spontaneously disappeared in about 2 hours. We decided to test Chrysaora hysoscella dermotoxicity on healthy volunteers by cutting a Chrysaora hysoscella tentacle and placing it on a gauze soaked in a solution of 3% NaCl and applying then to the volar side of the right wrist for one minute. Both volunteers presented itching and burning within forty seconds of contact. Three minutes later erythematous and vesicular lesions appeared on the sting site. To the best of our knowledge this is the second reported but first documented report of the dermotoxic effect of Chrysaora hysoscella. We underline that the absence of other previous reports may be due to both the relative rarity of this jellyfish and to the fact that people often confuses Chrysaora hysoscella with other more common jellyfish. PMID- 2576553 TI - [Preparation and evaluation of anti-human growth hormone immunoserum]. AB - Using small dosage of human growth hormone to immunize rabbit or guinea pig, it is able to induce anti-hGH antibody formation with high titre and high affinity that could be applied to hGH RIA. In the present study five rabbits and three guinea pigs were immunized with 125-200 micrograms and 250-285 micrograms per animal of hGH respectively, followed by boosters of 10-20 or 160-250 micrograms of hGH at 2-4 week intervals for 6 or 3 months. Blood was drown 1-2 weeks before each booster for determination of antibody formation. Antibody titre and affinity were successively observed and specificity of antibody was determined for the final bleeding. It was shown that titres of immune sera from guinea pigs were much higher than those of rabbit immune sera, but vice versa for antibody affinity. This might be due to larger immunogen dose used for guinea pigs than for rabbits. Fourteen different peptide hormones were tested in reference to cross-immunoreactivity to anti-hGH antibody. It could be demonstrated that the major cross-reactive hormones are hFSH and hLH, and hTSH also reacts to rabbit anti-hGH immune sera at a lesser degree. These cross reactivities are obviously owing to the molecular homogeneities between hGH and these hormones especially of their alpha-subunits. PMID- 2576556 TI - Extracellular ciliary axonemes associated with the surface of smooth muscle cells of ctenophores. AB - We describe the first example of bare ciliary axonemes existing outside eukaryotic cells. The axonemes run in longitudinal invaginations of the surface membrane of giant smooth muscle cells in ctenophores. No motility of the surface associated axonemes has been detected in living muscles. The axonemes are truly extracellular and in direct contact with the extracellular matrix (mesoglea), as shown by the ultrastructural tracer horseradish peroxidase. The axonemes appear partially degraded and disorganized, and individual doublet microtubules are difficult to distinguish. Nevertheless, immunofluorescence microscopy shows that the axonemes retain antigenic sites reacting with mouse monoclonal anti-beta tubulin. The origin of the extracellular axonemes is unknown: no attached basal bodies (extracellular or intracellular) have been found. The muscle-associated axonemes may play a unique role in smooth muscle function and/or development, and may be related to the evolution of muscle cells in soft-bodied invertebrates that exploit cilia for a wide variety of functions. PMID- 2576555 TI - Immunohistochemical demonstration of tyrosine hydroxylase, serotonin and neuropeptide tyrosine in the epithelioid cells within arterial walls and carotid bodies of chicks. AB - By immunolight and electron microscopy, the epithelioid, granule-containing cells within the wall of circumscribed portions of the thoracic aorta, the common carotid artery, the carotid body artery and those composing the carotid body itself of newly hatched chicks were shown to contain serotonin (5-HT), neuropeptide tyrosine (NPY) and tyrosine hydroxylase (TH). No nerve fibres immunoreactive for any of these three substances were found in relation to the granule-containing cells. All the granule-containing cells were immunoreactive for 5-HT. The proportion of 5-HT cells simultaneously immunoreactive for NPY or TH in the total cell population varied in different portions of the arteries and the carotid body: NPY-immunoreactive cells were more numerous in the thoracic and common carotid arterial walls, while TH-immunoreactive cells were much more numerous in the carotid body. Since the granule-containing cells within the arterial wall, because of similarities in their anatomical features to the carotid body, are presumed to function as the arterial chemoreceptor, the difference in content of the amines and peptides among the granule-containing cells in different locations may reflect some differences in the chemoreceptive mechanism between the cells in different locations along the thoracocervical arterial tree. PMID- 2576557 TI - Severe T lymphocyte immunodeficiency associated with hypogammaglobulinemia: defective lymphokine secretion but enhanced autologous mixed lymphocyte reaction. AB - The multiparameter immunologic study of T cells of a patient with acquired hypogammaglobulinemia was investigated, since he had a normal B-cell number and function. His peripheral blood lymphocytes were found to contain predominant CD4+ CD45R+ T cells with a clear deficiency of CD4+ CDw29+ as well as CD8+ T cells. His T cells proliferated in response to phytohemagglutinin (PHA) and pokeweed mitogen (PWM), but no immunoglobulin was secreted in PWM-induced patient's T-cell and normal B-cell differentiations. His T cells were also found to possess concanavalin A (Con A)-induced suppressor function when cocultured with normal T cells, as well as IgG-, IgA-, and IgM-specific suppressor function on PWM-induced normal T- and B-cell differentiations. The patient's T cells were found to secrete elevated amounts of interleukin-2 but failed to secrete two important B cell stimulating factors, B-cell growth factor and B-cell differentiation factor, in response to PHA. An investigation of immunoregulatory T-cell function in the autologous mixed lymphocyte reaction (AMLR) and allogeneic mixed lymphocyte reaction (MLR) indicated that the patient's T cells produced an enhanced AMLR but were deficient in MLR. These results suggest that the abnormalities we have identified in this patient with hypogammaglobulinemia reflect an intrinsic defect of T cells in the humoral immune response to produce three major immunoglobulins. PMID- 2576559 TI - Arthroscopic evaluation of traumatic injuries to the ankle and foot. Part I: Acute injuries. AB - Traumatic osseous and soft tissue injuries of the ankle have enjoyed significant attention in the world literature. Technologic advances over the past 3 decades have allowed investigators to develop parallel methods of treatment of surgical approaches to fractures and soft tissue injuries of diarthrodial joints. The result is the art, science, and technology of arthroscopic surgery. PMID- 2576561 TI - Traumatic classifications of the foot and ankle. AB - Many authors have presented classification systems for traumatic injuries to the foot and ankle. These systems of classification have been based on many factors (e.g., mechanism of injury, fracture pattern, fracture position and location). The most commonly used traumatic classification systems of the foot and ankle are reviewed. The staging, mechanism of injury, radiologic appearance, diagrammatic and radiologic examples are discussed. PMID- 2576558 TI - Serum and effector-cell antibody-dependent cellular cytotoxicity (ADCC) activity remains high during human immunodeficiency virus (HIV) disease progression. AB - The activity of both serum and effector cell antibody-dependent cellular cytotoxicity (ADCC) against human immunodeficiency virus (HIV-1, HIV) was assessed in HIV-infected individuals. The goal was to relate ADCC levels with the stage or progression of HIV disease. Serial serum samples, usually collected at 6 month intervals, from individuals at defined stages of HIV disease (seroconversion, the HIV-seropositive period before AIDS, and around the time of clinical AIDS diagnosis) were tested. HIV-coated CEM tumor cells were used as targets. Effector-cell ADCC activity was evaluated using fresh peripheral blood mononuclear cells (PBMC) from HIV-infected individuals at different stages of HIV disease. Samples were obtained from male homosexual participants in the Multicenter AIDS Cohort Study (MACS). In seroconverters, ADCC-inducing HIV specific antibodies were detected at the time that the ELISA antibody test was first positive. Within several months, serum ADCC activity stabilized in each individual. In 29 HIV-seroprevalent individuals (HIV seropositive on their first visit), serum ADCC activity remained constant regardless of whether the individual's HIV disease was stable (high stable CD4; n = 9) or rapidly deteriorating (sharply declining CD4, n = 10; AIDS progressors, n = 10). With respect to effector-cell activity, PBMC from HIV-infected individuals with or without AIDS were capable of mediating ADCC with heterologous and usually with autologous sera. Although the level of NK cytotoxic activity and the level of antibody-armed effector cell activity have been reported to decline as disease progresses, our results support previous observations that ADCC effector-cell activity against antibody-coated targets does not decline in HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576560 TI - Isolated fractures of the cuboid bone: two case reports with review of the literature. AB - Two rare cases of isolated fractures of the cuboid bone caused by indirect trauma are presented, in order to review the present literature. Hitherto, nine cases have been published. A possible mechanism of indirect trauma leading to isolated fracture of the cuboid bone is described. Fracture of the cuboid bone in both cases, results in development of arthritis around the cuboid. The management applied was immediate immobilization for 6 weeks followed by, respectively, an arthrodesis and an arthroplastic operation. Follow-up evaluation revealed unsatisfactory results in both cases. PMID- 2576562 TI - Diagnostic imaging of trauma to the ankle and foot. Part V: Midfoot injuries. AB - The authors have provided a series of dialogues dealing with the subject of trauma to the foot and ankle. Previous information was presented on ankle fractures, ligament injuries, talar and calcaneal maladies. The present discussion reviews pathology of the midfoot region. PMID- 2576563 TI - [Loss of heterozygosity in human tumors]. PMID- 2576564 TI - Observation on 38 cases of drug-induced myospasm treated with massage over the acupoints. PMID- 2576565 TI - [Neurohormones coming from the normal and tumoral human anterior pituitary. Secretion and regulation in vitro]. AB - Several neuropeptides, classically associated with the hypothalamus have been found in the anterior pituitary and their local synthesis has been hypothesized. Using normal and tumoral human pituitaries we found in the tissue itself different neuropeptides (TRH, SRIH, GHRH) and dopamine in variable quantities according to the nature of the tissue. They were all present in normal pituitaries while only stimulatory neurohormones like TRH and GHRH were found in tumoral tissue implying an imbalance between the stimulatory and inhibitory control of hypophyseal hormones (PRL and GH) in pituitary adenomas. Fragments from normal pituitaries and dispersed cells from GH, PRL and nonsecreting adenomas, were perifused for 4 hours in a Krebs-Ringer medium collected every 2 min and GH, PRL, TRH, GHRH and SRIH were measured by RIA under basal conditions and in the presence of 10(-6) mol/L DA, TRH or SRIH. Neuropeptides and DA were characterized by HPLC. Both normal and tumoral pituitaries released TRH, SRIH and GHRH in large amounts suggesting their local synthesis. There was an in situ regulation between SRIH and GH as their secretion profile was negatively correlated, GH secretion decreasing while SRIH secretion was increasing. Moreover the release of TRH was stimulated 5 to 20 folds by DA, while PRL decreased at the same time. Pulses of TRH and SRIH had differential effects on GHRH and SRIH release according to the nature of the tissue as TRH stimulated SRIH release from normal pituitary while it inhibited SRIH release from adenoma. These results indicate that anterior pituitary cells can release neuropeptides which are probably endogenously synthesized and have a local regulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576566 TI - [Course of acute hepatitis B in alcoholism]. AB - Clinical course of the acute hepatitis B has been analysed in 29 men chronically abusing alcohol. The most frequent source of the infection was surgery and hospitalizations. Clinical course and biochemical findings were similar in this group and in 30 men not drinking alcohol. A sole difference concerned higher GGTP activity in alcoholics. The persistence of HBs antigen was similar in both groups. Chronic alcohol abuse does not seem to have a significant effect on the course and convalescent phase of the acute hepatitis B. PMID- 2576567 TI - [Neurotransmitter mechanisms in stress and their role in the pathogenesis of depression; preclinical tests]. PMID- 2576568 TI - Prediction of change in borderline personality disorder. AB - Prediction of change in borderlines is an important effort because it may illuminate the character of this tentatively defined, complex disorder. In future years the disorder will be defined differently in light of its network of relationships with other variables. Presently, the strongest predictors of change in borderlines are receipt of neuroleptics and presence of target symptoms that are affected by these drugs. Other drugs and other treatments may also be found to have a selectively differential effect in which case receipt of these drugs will also predict change but perhaps on other target symptoms. Preliminary evidence implicates monoamine oxidase inhibitors (MAOIs), lithium, and carbamazepine. Response to thiothixene has been found to be related to the patient's Minnesota Multiphasic Personality Inventory (MMPI) profile prior to treatment. Biological predictor variables studied in other disorders have been found to be abnormal in borderlines, but how these variables might relate to change has not been studied. The program of research that is necessary includes other drug treatments, nonphysiological treatments, family history, and personality variables. PMID- 2576569 TI - [AIDS--the most important events in 1988. The London Declaration. Resolution on avoiding discrimination]. AB - Two documents are discussed whose acceptance the author considers as the most important events in 1988 in the control of AIDS, that is the London Declaration and the Resolution of the 41st World Health Assembly concerning avoiding of discrimination of subjects infected with HIV and AIDS patients. Both these documents are of essential epoch-making importance for facilitation of the trend of the further prophylactic actions conducted for halting the AIDS epidemic in the whole world. PMID- 2576571 TI - [Use of beta blockaders in pulmonary hypertension in patients with liver diseases]. PMID- 2576570 TI - [Adult Culicidae mosquitoes in the irrigated culture of rice in the Vale do Ribeira, State of Sao Paulo, Brazil]. AB - A collection of adult Culicidae was carried out during the period from May 1984 to September 1985, in a rice field in the polder of the Experimental Station of Pariquera-Acu, in the Ribeira Valley (S. Paulo State, Brazil). CDC miniature traps, supplemented with dry ice, were used. A total of 2,686 mosquitoes were collected. The most frequent were the Coquillettidia and Mansonia genera (nearly 55% of the specimens caught). Aedes scapularis, as an isolated species, contributed with near by 11% of the total catch. Culex (Melanoconion) represented almost 24% of the mosquitoes caught. The sequence of events involved in the flooding of rice seems be associated with the production of Coquillettidia and Mansonia. Ae. scapularis seems to profit from the artificial ecotope represented by the irrigated rice field as a means by which to increase its adaptation to the artificial human environment. No evidence was obtained on the association between Culex (Melanoconion) catches and the cultivation of the rice field. It seems that cultivation exercises no influence on the local Anopheles and Psorophora species. PMID- 2576572 TI - [Evaluation of the value of testicular phlebography]. AB - The authors use testicular phlebography since 1979; they examined so far 72 patients (62 children and 10 adults). Phlebography was indicated in 54 patients with varicocele and in 18 children with an unpalpable testicle. The authors evaluate the method with regard to the surgical procedure in the treatment of varicocele. In unpalpable testicles phlebography proves in some cases useful in the differential diagnosis. The authors evaluate the importance of the examination. The new findings regarding anatomical and functional aspects are, no doubt, valuable. On the other hand, the authors draw attention to the complicated examination (in particular in children) to the invasive character of the examination and the irradiation load. PMID- 2576573 TI - [Tumors of the adrenal medulla: nosologic profile and diagnostic technics]. AB - A nosologic re-arrangement of medullo-adrenal neoplasms has been looked for in this article, with particular regard to their common relationship to the complex histogenic system descending from the neuroectoderma-neural crista. The morpho biologic features of these clinical entities are also reviewed, as well as the up to date laboratory and imaging techniques, with a stress on the high sensibility and specificity levels afforded, e.g., for some of these tumours by selected radio-isotopic examinations, due to their histogenetic, thereby biologic peculiarities. PMID- 2576574 TI - Guidelines for the use of psychopharmaca in geriatric cases. AB - The use of psychotropic drugs in elderly patients requires special knowledge of both clinician and general practitioner. Considering the pharmacokinetic and pharmacodynamic changes characteristic of the senile organism, relatively few of the great variety of psychotropic drugs may be used in geriatrics. After giving a survey of the kinetics and mechanism of action of drugs from geriatric aspects the use, indications and contraindications, unwanted side-effects, the risks of interactions of neuroleptics, antidepressants, minor tranquillizers and hypnotics have been discussed in detail. The principles of gerontological lithium therapy have been summarized and the clinical importance of the so-called geriatrics (including the so-called nootropics) has been subjected to criticism. The author emphasizes the primary importance of psychotherapy and sociotherapy as adjuvants to psychotropic treatment. PMID- 2576575 TI - Results obtained with Loderix tablet in chronic rhinitis patients. AB - The place of histamine among primary mediators in allergic rhinitis and the mechanism of action of antihistamines have been discussed. The use of Loderix was tried in 40 chronic rhinitis patients by the open method. According to the observations the second generation Loderix may be successfully used in allergic rhinitis and "eosinophil" type vasomotor rhinitis cases. The side-effects of Loderix did not differ from those of the other antihistamine products. PMID- 2576577 TI - [Periarteritis nodosa with clinical manifestations of acute cholecystitis]. AB - A 69-year-old male patient is reported with clinical symptoms and signs of acute cholecystitis in whom microscopic examination of the surgically removed gallbladder showed evidence of periarteritis nodosa. PMID- 2576576 TI - [Epidural anesthesia with a combination of narcotic analgesics and local anesthetics in the surgical treatment of arterial occlusion of the leg]. AB - Comparative characteristics of epidural anesthesia with local anesthetics and a combination of the latter with narcotics in the reconstruction of arterial segments of lower extremities in 123 patients were given. The use of narcotics decreases the frequency of introduction of the drugs into the epidural space, does not induce persistent arterial hypotension and practically excludes different complications associated with epidural anesthesia. PMID- 2576578 TI - [Hemorheologic effects of calcium antagonists in comparison with beta receptor blockers]. AB - Normalizing rheological deficits may enhance perfusion. Both betablockers and calcium antagonists induce such effects in various populations due to differing mechanisms. In the case of calcium antagonists, this could synergistically contribute to a reduction of the peripheral resistance, predominantly caused by vascular changes. This hypothesis requires experimental testing. PMID- 2576579 TI - Typing of Listeria monocytogenes for epidemiological studies using DNA probes. AB - We have investigated the possibility of using restriction fragment length polymorphisms (RFLPs) to distinguish different strains of Listeria monocytogenes. Cloned DNA fragments (probes) were selected from a bacteriophage lambda gene library of L. monocytogenes (L1428). DNAs from two lambda clones consisting of a total of approximately 20kb of probe DNA were labelled with biotinylated dUTP for use in these experiments. The criteria for probe selection were the ability both to hybridise with all strains of L. monocytogenes and to reveal RFLPs. Southern blots of restriction endonuclease (Nci I) digested DNAs from test strains of L. monocytogenes were hybridized to the probe. Following washing, biotinylated probe remaining bound to the filters was detected using the Blugene reagents (Gibco/BRL). Under these experimental conditions strain-specific restriction fragments were revealed. We have examined 64 strains of L. monocytogenes belonging to serogroup 1/2 which were not apparently epidemiologically associated and 19 patterns were observed. Epidemiologically related strains gave identical patterns of restriction fragments. PMID- 2576580 TI - In situ detection of DNA-binding proteins in herpes simplex virus type 1-infected cells. AB - An in situ assay for detecting DNA-binding proteins in herpes simplex virus type 1 (HSV-1)-infected cells is described. Seventeen HSV-induced DNA-binding species were visible with nicked, double-stranded DNA as a substrate, while fourteen virus-induced DNA-binding fractions were present in gels containing nuclease treated, single-stranded DNA. The effects of HSV on cellular DNA-binding protein expression could also be seen. The resolution of DNA-binding fractions was dependent upon the type of DNA substrate utilized, high salt extraction of DNA binding components and their physical separation from infected cell DNAs, dialysis of the high salt and the length of DNase treatment of gels following electrophoresis. PMID- 2576581 TI - BLV-p24 expression in BLV infected cattle and detection of BLV-p24 receptors in cattle afflicted with tumorous leukosis in vivo. AB - Noncultivated and short-term cultivated blood leukocytes of BLV-infected cattle both with and without tumorous leukosis have been investigated for BLV-p24 antigen expression and for their capacity to bind BLV-p24 antigen. In animals with persistent lymphocytosis using cell extracts of 3-6 X 10(8) non-short-term cultivated blood leukocytes, BLV-p24 antigen could be identified by means of competitive RIA. In cattle with tumorous leukosis, the antigen detection in non short-term cultivated leukocytes may be masked by the presence of antigen-binding receptors. The capacity of p24 antigen binding is likely to be a phenotypical marker for the cells occurring in the tumour phase only. PMID- 2576582 TI - Semipurified human leukocyte ultrafiltrate in herpes zoster. I. Large-scale preparation and biochemical analysis. AB - Nine batches of lysed human leukocyte ultrafiltrate (LLU) prepared from buffy coats of random healthy donors, as well as their semipurified subfractions--P2/II -were compared in terms of protein, orcinol-reactive material (ORM) content, and ratios of the average values of their ORM and protein contents. Two-step ethanol precipitation and size exclusion chromatography on Sephadex G-15 were used for partial purification and concentration. In comparison to the starting material, approximately 4.4 - fold increase in the ORM/protein ratio of P2/II has been effected. Relatively high variation in both, protein and ORM content of the crude LLU individual batches (ranges: 365 micrograms/1 ml - 962 micrograms/1 ml; 157 micrograms/1 ml - 660 micrograms/1 ml, respectively), as well as of those of P2/II fractions (ranges: 16.5 micrograms/1 ml - 207.5 micrograms/1 ml; 150 micrograms/1 ml - 480 micrograms/1 ml, respectively) could be observed. The suggested combined purification procedure removed from the LLU about 85% proteins and 33% ORM. The removed material contained inhibitors of the cell-mediated immunity (CMI)-inducing and/or augmenting properties of LLU. This is in good agreement with the observed improved therapeutic effect of P2/II fraction in herpes zoster treatment of otherwise noncompromised adults, as described in the companion paper. PMID- 2576583 TI - Increased migration inhibition factor production by leukocytes of patients with herpes zoster given the leukocyte ultrafiltrate. AB - Using the direct leukocyte migration inhibition assay, the cell-mediated immune response was followed in together 47 patients suffering from herpes zoster. Of these, 19 persons were treated with partially purified and concentrated lysed leukocyte ultrafiltrate. Enhancement and/or earlier production of the leukocyte migration inhibition factor--in the presence of varicella-zoster virus antigen- was observed by leukocytes from patients given the ultrafiltrate on days 2-3 since the onset of the vesicular stage of the disease. Highly significant (alpha = 1%, P less than 0.01) differences in the migration inhibition values were observed between non-treated patients and patients given one dose of the ultrafiltrate during the days 3-12 after appearance of the first herpes zoster vesicles; on days 13-30 these values were not significant. PMID- 2576584 TI - Some immunological characteristics of subjects suffering from frequent herpes simplex virus recrudescences. AB - Some parameters of specific and non-specific immunity were tested in a group of 44 subjects suffering from frequent herpes simplex type 1 (HSV-1) or herpes simplex type 2 (HSV-2) recrudescences. The tests performed included determinations of (i) HSV complement-independent and complement-dependent neutralizing antibodies, (ii) antibodies to glycoprotein C of HSV-1 and glycoprotein G of HSV-2, (iii) antibodies to viral capsid and early antigens of Epstein-Barr virus, (iv) antibodies to tetanus toxoid, (v) serum levels of IgM, IgG, IgA, transferrin, prealbumin and C'3 and C'4 components of complement, (vi) active and total T lymphocytes, (vii) phagocyting activity of polymorphonuclear neutrophils, eosinophils and mononuclear cells, (viii) skin reactivity to tuberculin, toxoplasmin, candidin, tetanus and diphtheria toxoids. In the patients the following deviations from the control groups were noted: (i) Antibody levels to homotypic but not to heterotypic HSV were enhanced, (ii) serum IgM levels were elevated, (iii) percentages and numbers of active and total T lymphocytes were decreased, (iv) phagocyting activity of neutrophils was depressed but that of eosinophils was increased. PMID- 2576585 TI - Restriction endonuclease analysis of the DNA of Rickettsia prowazekii vaccine strain E and its revertant. AB - The DNA of Rickettsia prowazekii vaccine strain E was analysed by restriction analysis with 17 endonucleases in comparison with its virulent revertant - Evir and the virulent reference strain Breinl. The DNA of cloned and uncloned strains showed identical restriction endonuclease patterns. In spite of stable differences in virulence, strains E and Evir displayed a totally identical DNA cleavage pattern indicating the absence of marked structural differences between their genomes. On the other hand 9 endonucleases showed differences in the restrictograms of the DNA strain Breinl as compared with strains E and Evir. PMID- 2576586 TI - Interaction between Dermacentor reticulatus cells and Coxiella burnetii in vivo. AB - By electron microscopy the distribution of Coxiella burnetii was followed in females of Dermacentor reticulatus injected intracoelomally in a dose of about 10(3) EID50 per tick. The heaviest infestation with coxiellae was noticed in the cells of haemolymph, fat body, Malpighian tubulus and tracheal complex. No rickettsiae were found in Gene's organ. Unexpected was the propagation of rickettsiae in muscle fibres. C. burnetii multiplied in all organs affected. Heavy infection resulted at the marked damage of cell components. Coxiellae were evident in the haemocytes; in organs they formed small and large cell variants; endospore formations were observed free in the haemolymph. PMID- 2576587 TI - Cell-mediated immune response to Coxiella burnetii antigens in Q fever convalescents and vaccinees. AB - Cellular immunity against phase I and II Coxiella burnetii antigens was evaluated by the lymphocyte blast transformation test in a) Q fever convalescents; b) persons immunized with a chemovaccine against Q fever; and c) control persons. The first two groups consisted of workers in a ricketsiology department. Of the 9 convalescents, all (100%) were positive against phase I antigen and 4 (44.4%) against phase II antigen. Of the 22 vaccinees, 77.3% were positive against phase I antigen and all were negative against phase II antigen. All 10 controls were negative against both antigens. PMID- 2576588 TI - Viral vaccines: achievements and challenges. AB - In this review the present state of vaccination as a means to control viral diseases is discussed, and the needs and directions for future investigations are considered. The history of viral vaccines already in use is surveyed for guidance in what steps and background knowledge of the viral agents and the host responses to infection were necessary to their successful development. The steps requisite for demonstrating efficacy and safety of a viral vaccine also are summarized, and the features of the target populations to be protected are noted as they affect the final requirement for a successful vaccine: that it be administered in proper dosage and potency to those who need it. General remarks on the proper use of current vaccines are followed by an overview of various developments toward prospective vaccines, along with the predicted time-frames for their coming into general use. Vaccines considered include vaccines to be administered locally at the portal of entry, subunit vaccines, viruses attenuated by genetic manipulation, use of viral vectors, vaccines developed by means of recombinant DNA, synthetic peptides, and anti-idiotype vaccines, as well as new vaccines being developed by more conventional methods. PMID- 2576589 TI - Classification of tick-borne flaviviruses. PMID- 2576590 TI - Isolation of human immunodeficiency virus from the blood of lymphadenopathy patient from Bratislava. PMID- 2576591 TI - Expression of envelope glycoprotein (E) of Japanese encephalitis virus by recombinant vaccinia virus. AB - Vaccinia virus recombinants inserted with cDNA clones of Japanese encephalitis (JE) virus envelope glycoprotein (E) gene were constructed. The E gene product was detected in the recombinant virus-infected BHK21 cells by immunofluorescence (IF) and Western blotting. The intensity of IF observed was higher by the recombinant of the TK promoter--P7.5 promoter--inserted cDNA construct than by the P7.5 promoter--TK promoter--inserted cDNA construct. The E gene product was hardly detected by the recombinant carrying the TK promoter only upstream to the inserted cDNA, although the glycoprotein E mRNA had been transcribed. PMID- 2576592 TI - Inhibition of influenza virus haemolytic and haemagglutination activities by monoclonal antibodies to haemagglutinin glycopolypeptides HA1 and HA2. AB - Acid treatment of influenza virus enhanced haemagglutination inhibiting (HI) activity of some anti-HA1 monoclonal antibodies (MoAbs). These changes in the HI activity could be either due to alteration in the mutual orientation of MoAb (e.g. IC8, IB8) binding epitope to receptor site or to an increase in the number of epitopes accessible to the corresponding MoAbs (e.g. IVA1). HI test with pH 5 virus revealed similar (although not identical) antigenic differences among related virus strains as the HI test with pH 7-virus. Anti-HA2 MoAbs were negative in the HI test with both pH 5- and pH 7-virus. Anti-HA1 MoAbs showed a HI activity with pH 5-treated BHA similar to that with pH 5-treated virus. Surprisingly one out of eight anti-HA2 MoAbs (IIF4) exhibited a relatively high HI activity to pH 5-BHA-mediated haemagglutination. Virus-induced red blood cell haemolysis was efficiently inhibited with several anti-HA1 MoAbs (e.g. IC8, IB8, and IIB4) while other anti-HA1 antibodies, including IVA1 and IVG6 with preferential reactivity with pH 5-treated antigens in RIA, gave no inhibition. As a rule, anti-HA2 MoAbs were poor haemolysis inhibitors. PMID- 2576594 TI - Complement-dependent cytotoxicity of antibodies reactive with HIV-induced cell surface antigens in HIV-carrying haemophiliacs. AB - Sera obtained from HIV-infected as well as uninfected haemophiliacs and from healthy subjects were investigated for the presence of lymphocytotoxic antibodies. Using the 51Cr-release test, HIV-infected haemophiliacs were found to produce serum antibodies exerting complement-dependent cytotoxic effect on HIV infected T4 cells. The antibodies were reactive mainly when HIV-infected target cells were stimulated with concanavalin-A. Results of complement-dependent antibody cytotoxicity and indirect membrane immunofluorescence tests suggest that envelope antigen(s) of HIV may be the target(s) for cytotoxic antibodies. PMID- 2576593 TI - Involvement of carbohydrates in vesicular stomatitis virus-cell early interaction. AB - The role of N-acetylneuraminic acid and N-acetyl-D-glucosamine containing molecules in vesicular stomatitis virus-cell interaction was studied using specific lectins (limulin and wheat germ agglutinin) and esoglycosidases (neuraminidase, beta-galactosidase, alpha-mannosidase, alpha-fucosidase, beta-N acetyl-D-glucosaminidase). Lectin treatment of vesicular stomatitis virus (VSV) indicated that carbohydrates of the VSV G envelope glycoprotein were not required for virus infectivity, whereas sialic acid appeared directly involved in the attachment of virus to erythrocytes. The comparative results obtained after enzymatic digestion of cell membrane carbohydrates or their cross linking by lectins demonstrated that whereas VSV infectivity was strongly reduced by pretreatment of chick embryo cells, virus binding to erythrocytes was unaffected by such treatments. We conclude that sugar residues may participate at the host cell attachment site which differs, at least in part, from the membrane binding site of erythrocytes. PMID- 2576595 TI - Rabies-related Yuli virus; identification with a panel of monoclonal antibodies. AB - Yuli virus was isolated by intracerebral (i.c.) inoculation of suckling mice with a 10% brain suspension from 11-year-old patient who died under signs of atypical hydrophobia after a bat bite into lower lip. Identification with a panel of monoclonal antibodies (MoAb) to nucleocapsid protein (NP) confirmed that Yuli virus belongs to Lyssavirus genus, as an antigenic variant of the European Duvenhage virus. PMID- 2576596 TI - Murine monoclonal antibodies against human fibroblast (beta) interferon. Correlation of the neutralization of antiviral and antiproliferative activities. AB - Eight mouse hybridoma lines secreting monoclonal antibodies (MoAb) to human fibroblast interferon (HuIFN-beta) were established. All MoAbs were capable of neutralizing two different biological activities of HuIFN-beta: the antiviral activity and the antiproliferative activity. Positive correlation was demonstrated between the ability of hybridoma culture supernatants to neutralize the antiviral and antiproliferative effects of human fibroblast IFN. The neutralizing capacity of individual hybridoma culture supernatants depended on the concentration of MoAb in the sample. Only one of IFN-neutralizing MoAbs has shown binding capacity to human fibroblast IFN when used in enzyme immunoassay as solid-phase antigen. This MoAb was purified to homogeneity and its specific neutralizing activity against HuIFN-beta was calculated (3.5 X 10(4) I.U. per mg). PMID- 2576597 TI - The process of baculovirus deproteinization. AB - The localization and function of alkaline protease inside the supervirion capsids (granules, inclusion bodies) of granulosis virus and nuclear polyhedrosis virus have been determined with the help of electron microscopy. It has been shown that deproteinization of baculoviruses proceeds in several steps. The first two stages (the release of virus from supervirion capsids and the release of nucleocapsids from the internal and external coats, were accomplished in the intestine of the insects, while the third stage (the release of nucleic molecules from the nucleocapsids) took place in the nucleoplasm of intestinal epithelial cells. PMID- 2576598 TI - Enhancement of plaque formation of herpes simplex virus (HSV) and varicella zoster virus (VZV) by subinhibitory dose of acyclovir (ACV). AB - Acyclovir (9-/2-hydroxyethoxymethyl/guanine) enhanced the plaque formation of HSV and VZV at subinhibitory dose and inhibited at higher concentration but not in thymidine kinase deficient viruses. The enhancement was neutralized by thymidine. Induction of viral thymidine kinase activity was not affected with ACV. These results suggest that the enhancement may be mediated by viral thymidine kinase. PMID- 2576599 TI - Lack of antiviral activity of ketoconazole alone or in combination with the acyclic nucleoside ganciclovir against a herpes virus type 2 infection in mice. AB - Ketoconazole and ganciclovir were tested for antiviral activity, each alone and in combination, against a herpes simplex virus type 2 (HSV-2) systemic infection in Swiss-Webster mice. When given once daily for 5 days starting 24 hr after infection, the ED50 for ketoconazole either alone or in combination was greater than 60 mg/kg; for ganciclovir, the ED50 was 7.1 mg/kg alone and 10.8 mg/kg in combination. Thus, ketoconazole did not potentiate or antagonize the antiviral activity of an acyclic nucleoside. Consequently, AIDS patients could perhaps receive ketoconazole and ganciclovir simultaneously for fungal and viral opportunistic infections without interference with their respective efficacies. PMID- 2576601 TI - Virus-like particles in Dermacentor reticulatus ticks. AB - Virus-like particles were found in the brain and salivary glands of Dermacentor reticulatus ticks double infected with Coxiella burnetii and Rickettsiella phytoseiuli. The particles were spherical (diameter of about 70 nm) and consisted of an electron-dense inner core and a dense external coat. PMID- 2576600 TI - Further evidence of the circulation of PMV-4 and influenza viruses with N2-1957 enzyme in the migratory waterfowls. AB - In the years 1980-1984, one paramyxovirus type 4 and 11 influenza viruses were isolated from cloacal swabs collected from migratory waterfowls in Fed. Rep. Germany. One influenza virus of H4N8 subtype was isolated from swabs of commercial ducks collected at an abbatoir. Seven of 10 influenza strains, isolated from mallard ducks and coot were identified as a mixture of 2-3 strains of H1, H4, and H5 subtype; 3 virus strains from the same locality relate antigenically to subtype H4 with enzyme serologically identical with N2- Singapore/57 as demonstrated by means of polyclonal and monoclonal antibody. PMID- 2576602 TI - An alternative approach for induction of chromosomal banding and preservation of chromosomal morphology for virus DNA mapping by in situ hybridization. AB - I report on the use of acetic/saline/Giemsa technique for the induction of chromosome banding and an additional fixation (prior hybridization) to preserve the chromosome morphology as regards in situ hybridization under stringent conditions. This approach results in high quality banding resolution for grain localization of integrated sites of virus DNA sequences on both metaphase and prometaphase chromosomes. PMID- 2576603 TI - The preparation of antiidiotypic antibodies against human beta-interferon. PMID- 2576604 TI - The pathogenic potency of rotaviruses. PMID- 2576605 TI - [Complications and failures in lumbar disk surgery]. PMID- 2576606 TI - [Surgical approaches in intra- and extracanalicular lumbar intervertebral disk displacement. Technical considerations]. PMID- 2576607 TI - [An extra-foraminal approach to extreme lateral disk hernia]. PMID- 2576608 TI - [Chronic lumbar vertebragenic pain, pathomechanism and diagnosis]. PMID- 2576609 TI - [Painful postoperative lumbosacral fibrosis and its treatment with electrical posterior cord stimulation]. PMID- 2576610 TI - [Facet denervation following disk surgery]. PMID- 2576611 TI - [Experiences with thermorhizotomy of the Luschka nerve in persistent ischialgia following unsuccessful intervertebral disk surgery]. PMID- 2576612 TI - [Surgery of the lumbar spine: results of a survey of 868 patients]. PMID- 2576613 TI - [Postoperative lumbar intervertebral discitis]. PMID- 2576614 TI - [Pelvic malposition as a cause of postoperative pain]. PMID- 2576616 TI - [Narrow lateral recess as a cause of recurrent radicular complaints]. PMID- 2576615 TI - [Results of 137 reoperations following treatment of lumbar disk hernia: the significance of osseous stenosis]. PMID- 2576617 TI - [Instability of the operated mobile segment following lumbar disc surgery]. PMID- 2576618 TI - [Instability following unilateral foraminectomy in extreme lateral disk hernia]. PMID- 2576619 TI - [Procedures in instability of the operated mobile segment following lumbar intervertebral disk surgery]. PMID- 2576620 TI - [Spondylolisthesis and disk hernia]. PMID- 2576621 TI - [Reoperation following intervertebral disk surgery]. PMID- 2576622 TI - [Transmission cycles of arboviruses in Madagascar]. AB - Some arboviruses are highly pathogenic for Men or animals. Arboviruses epidemiological patterns in Madagascar were determined by entomological, serological, and virological surveys. We listed potentials arboviruses vectors in Madagascar. Entomological results generated by us during five years, as well as prior to, are shown. We caught more than 150,000 hematophagous arthropods, belonging to 107 species at least. 3 of these species were new. 4183 inoculation pools were done. We studied serollogically (by HI test) samples collected from 563 animals and 626 Men. Our data, in agreement with others collected from 1965 to 1982, demonstrate that arboviruses circulate in the whole island. Positive reactions were obtained mainly with Flavivirus, in particular with West-Nile. Nine various arboviruses, including dengue-2 virus isolated from an individual having travelled to La Reunion, have been isolated. Dakar-Bat and Mengo virus have been observed. We studied transmission cycles of the following viruses: Babanki, West-Nile, Rift Valley Fever, Crimean-Congo Hemorrhagic Fever, MMP 158, Ngari, Perinet and Andasibe; the last 2 being endemics. In relation to Madagascar biogeographic characteristics (long-term isolation, scarce communications, high endemicity, and low vertebrate density), we evaluated the risk of potential introduction and amplification of various arboviruses (dengue, yellow fever, japanese encephalitis, Sindbis and Chikungunya). The risk is very high for dengue due to the presence of susceptible mosquitoes strains while the virus circulates in East Africa and in the Indian Ocean area. This risk seems to be very low for yellow fever, and intermediate for other arboviruses. PMID- 2576623 TI - [Age-related morphology today and tomorrow]. PMID- 2576624 TI - Multidrug resistance and P-glycoprotein expression in human cancer. PMID- 2576625 TI - [Amino acid sequence of a neurotoxin from the anemone Radianthus macrodactylus]. AB - Amino acid sequence of neurotoxin I isolated from the anemone Radianthus macrodactylus, and consisted of 48 amino acid residues, including six cysteines, was determined by analysis of products of its trypsin and chymotrypsin digestion. PMID- 2576626 TI - Few-minutes tests for the identification of group A streptococci and enterococci with chromogenic substrates. AB - The usefulness of paper strip tests for rapid identification of Streptococcus pyogenes and enterococci cultured on blood agar plates was investigated. The paper strips used contain dried chromogenic substrates for pyrrolidonyl peptidase (PYRase) and beta-glucosidase (beta-Gluc). Material from only a few colonies needed to be applied to the test strips. The reactions could be read after two min (PYRase) and 5-7 min (beta-Gluc), respectively. Results from testing 503 streptococcal strains were evaluated. The reactions proved very useful for rapid differentiation of S. pyogenes and enterococci from human sources. Nearly all strains of these streptococcal species showed positive reactions in the PYRase test whereas only the enterococci (E. faecalis and E. faecium) were positive for both enzymes. PMID- 2576627 TI - Efficacy of rifabutin in the treatment of AIDS-related complex. AB - We performed a phase 1-2 antiviral dose escalation trial of rifabutin, a rifamycin antibiotic with anti-HIV-1 activity in vitro. We followed 16 men with AIDS-related complex (ARC) for a mean duration of 29 weeks; the maximum toxicity limited dose of rifabutin was 2400 mg/day, which was achieved in two patients. There was some evidence of anti-HIV-1 activity in two patients, one of whom had an improvement in immune status, but 11 of the 16 patients showed a deterioration in either virologic or immunologic status. The majority of the patients under study remained clinically stable during the trial, but there was clinical deterioration in the three who entered with CD4 cell counts of less than 100 x 10(6)/l. On the basis of this trial, rifabutin as a single antiviral agent does not appear to be beneficial to ARC patients. PMID- 2576628 TI - Pilot phase I study using zidovudine in association with a 10-day course of anti CD4 monoclonal antibody in seven AIDS patients. AB - Experimental evidence has demonstrated that monoclonal antibody (MAb) 13B8.2, a workshop-qualified anti-CD4 MAb, (1) inhibits in vitro syncytium formation as well as in vitro HIV infection of CD4+ T cells; (2) delivers negative signals to T cells, thus preventing T-cell activation and viral replication; (3) contributes to CD4+ T-cell clearance by its Fc portion, and (4) induces an immune response by the patient, contributing potentially to an anti-idiotypic response of interest for the control of the immune parameters of the disease. On this basis a phase I study combining zidovudine treatment and a 10-day course of anti-CD4 MAb was performed in seven AIDS patients (Centers for Disease Control group IV). The treatment was well tolerated. MAb dosage and schedule were adjusted on the basis of circulating CD4+ cells and MAb pharmacokinetics; immunological and virological parameters were also monitored. One patient presented a transient increment in CD4+ T cells associated with augmented T-cell function, the suppression of p24 in the serum and a negative RT assay. A second patient had a steady increment of CD4+ T cells after completion of the treatment, with a transient decrease of serum p24 5 days after completion of the anti-CD4 protocol. PMID- 2576629 TI - Lack of activity of zidovudine in AIDS-associated Kaposi's sarcoma. AB - The efficacy of zidovudine (AZT) for treatment of patients with Kaposi's sarcoma as the initial manifestation of AIDS was determined in a non-randomized, phase-II clinical trial. Twenty-two patients were treated with zidovudine (300 mg 4 times daily for 8 weeks). In patients with stable disease or showing a response, treatment was continued. After 12 weeks the total daily dose was changed to 1000 mg. Only two of all 22 evaluable patients achieved a response (one complete and one partial response), of only brief duration (2 and 4 months, respectively). There was no such association between antiretroviral activity, increase in CD4+ cells and tumour response, as was reported during treatment with human recombinant interferon alpha (IFN-alpha). These findings do not support the use of zidovudine as a first-line treatment for patients with AIDS-associated Kaposi's sarcoma. PMID- 2576630 TI - An open study of interferon in HIV-antibody-positive men. AB - Alpha-2a-recombinant interferon (Roferon A) was given subcutaneously in a dose of 3 mega units twice weekly for 15-18 months to 14 HIV-antibody-positive, p24 antigen-negative men with minimal HIV-related disease. Interferon was well tolerated and safe. Although there was either improvement or lack of deterioration initially in 22 out of 26 HIV disease markers, including lymphadenopathy, thrombocytopenic purpura and nail fungal infection, there were 11 instances of HIV disease indicators appearing during the study. At 15 months, six patients were withdrawn from the study because of clinical and immunological deterioration. PMID- 2576631 TI - Improved genomic blot hybridization. AB - For restriction fragment length polymorphism (RFLP) and other molecular biology experiments, well prepared (undamaged) genomic DNA is needed, which is then digested with restriction enzymes, transferred to nitrocellulose paper and hybridized with radioactive or nonradioactive probe. DNA damage occurs in fields such as clinical genetics and forensic medicine in the form, for example, of single stranded breaks. If these DNAs are treated with T4 DNA ligase prior to restriction endonuclease digestion, the damaged DNA is repaired. This "repaired DNA" gives improved Southern hybridization results with single copy gene or repeated genes. PMID- 2576632 TI - Maturation promoting factor, cyclin and the control of M-phase. PMID- 2576633 TI - Hereditary factors in Takayasu disease. III. Polymorphism of human complements. AB - Genetic polymorphisms in C2, C4, C6, C7 and BF alleles of human complement were studied in 80 Japanese patients with Takayasu disease, and compared with those of 433 normal Japanese. Statistically significant high frequencies of C4A2 (chi 2: 27.2; p less than 0.01) and C4BQ0 allotype (chi 2: 8.7; p less than 0.01) were found in patients with Takayasu disease. Furthermore, all patients carrying C4A2 were found to be associated with C4BQ0. In addition, patients with HLA Bw52 were strongly associated with C4A2BQ0. In 5 patients homozygous C4BQ0 was found. These data suggest that some genetic factor(s) may contribute to the pathophysiological condition of Takayasu disease, which is strongly associated with the complotype of HLA Bw52-C4A2BQ0. PMID- 2576634 TI - Linkage of the Dao-1 gene for D-amino-acid oxidase to the pgm-1 gene for phosphoglucomutase-1 on the mouse chromosome 5. AB - Linkage of the Dao-1 gene controlling D-amino-acid oxidase to the Pgm-1 gene controlling phosphoglucomutase-1 on the mouse chromosome 5 was examined. Mutant ddY/DAO- mice carrying a null Dao-1c allele had a Pgm-1a allele. Mutant mice were crossed to C3H/HeN and NZB/Kl mice carrying the Dao-1+ and Pgm-1b alleles. The hybrid F1 mice were backcrossed to the ddY/DAO- and their progeny were examined for alleles for D-amino-acid oxidase and phosphoglucomutase-1. In both backcrosses, the progeny with recombinant-type combinations of the alleles were significantly less than the progeny with the parental-type combinations, indicating the linkage of the Dao-1 and Pgm-1 genes. The recombination frequency between these loci was estimated to be 19.8 +/- 4.0%. PMID- 2576635 TI - [Neuro-hormonal mechanisms in heart insufficiency--from physiopathology to treatment]. AB - This review updates some recent advances of a new and exciting developments in basic and clinical cardiology: a) the role, in the congestive heart failure (CHF), of the neurohormonal systems (NHS) which act to maintain circulatory homeostatic equilibrium, and b) the therapeutic implications of such a role. Six NHS, acting in CHF, have presently been identified: three of them induce vasoconstriction and sodium retention (sympathetic nervous systems, renin angiotensin-aldosterone system and arginine-vasopressine system); the remaining three offset or balance the former ones, acting, therefore as "counterregulators" (prostaglandins--PGE2 and PGI2--, dopaminergic system and atrial natriuretic factor). Each one of these NHS influences the "compensatory" mechanisms of heart failure, acting on the target-organs both by direct effects and by interaction with other NHS; consequently, in heart failure, all the NHS are stimulated with the respective increase in the plasma levels of their agents. In asymptomatic stages of ventricular dysfunction the stimulation of the vasodilator-and natriuretic systems appears to be predominant and able to maintain circulatory equilibrium. However, as the heart dysfunction increases and becomes symptomatic, the vasoconstrictor and sodium-retaining forces appear to predominate; this phenomenon becomes increasingly apparent as the functional class becomes more advanced. The hyperstimulation of these last systems has an extremely important role in the pathophysiology and clinical manifestations of congestive heart failure, as well as in its prognosis. Therefore, the attempts to correct these neurohormonal imbalance in patients with heart failure has a sound rational basis, not only to improve the symptoms and the exercise capacity but also to increase the survival of these patients. At the present time, amongst the potential pharmacological interventions acting on NHS in CHF, the blockade of the SRA system with ACE-inhibitors is generally accepted as the most feasible, the safer and the most effective therapeutic tool. In fact, its application has broadened from an earlier use in severe CHF to other symptomatic stages of cardiac failure, including the milder forms. In addition, preliminary data strongly suggest its unique usefulness in asymptomatic phases of ventricular dysfunction. Looking back at the medical therapy of heart failure, it can be concluded that we are starting a new era. Throughout 200 years (since the introduction of digitalis) the therapeutic goal in CHF has been the improvement of symptoms. With the developments of the present decade, a new and exciting goal is being offered to these patients, called by Packer "the second frontier", that is, the prolongation of their lives. PMID- 2576637 TI - [Epidural empyema; a complication of frontal sinusitis]. AB - Two patients are presented with extradural empyema originating from the frontal sinus. The infection spread was in the first case via the diploic veins through the intact sinus wall, and in the second case after the destruction of the posterior wall of frontal sinus. The early diagnosis methods and surgical drainage are discussed. Braid scan and Computed tomography are the most useful methods for the evaluation of this pathology. PMID- 2576636 TI - [Role of beta-blockers in the pharmacologic treatment of congestive heart failure]. AB - Beta-blockers are generally considered contra-indicated in heart failure. Some authors have claimed that in dilated cardiomyopathy and in pos myocardial infarction patients with heart failure beta-blockers can improve symptoms and survival. These trials and their conclusions are revised and the rationals of pathologic physiology of heart failure for this treatment are discussed. PMID- 2576638 TI - Immunohistochemical studies on the development of tyrosine hydroxylase- and serotonin-immunoreactive neurons in fetal dorsal raphe tissue transplanted into the anterior eye chamber of adult rats. AB - Pieces of tissue containing dorsal raphe nuclei of fetal rat brains were transplanted into the anterior eye chambers of adult rats. The differences between the developmental patterns of catecholaminergic and serotonergic neurons- especially the extension of their axonal processes--in the grafts were immunohistochemically examined using tyrosine hydroxylase (TH) and serotonin antisera. At an early stage after transplantation (3 days), TH-positive neurons appeared in grafts that had and had not been pretreated with a monoamine oxidase inhibitor (MAOI, Nialamide), while serotonin-positive neurons were demonstrated only in the grafts that had undergone MAOI pretreatment. Morphological differences in the growth pattern in the experimental milieu between the TH and serotonin neurons were also demonstrated: at this early stage, the somata of the TH neurons were multipolar and stellate shaped and possessed several distinct processes, while the serotonin neurons were ovoid shaped and lacked such processes. One week to 1 month after transplantation, the number of TH-positive fibers gradually increased, but their distribution was restricted to the area surrounding the cell bodies of the TH neurons in the graft. However, the processes of the serotonin neurons formed a dense plexus in the graft, and a small number of these fibers extended into the host iris 1 week after transplantation. By one month after the operation, the density of the serotonin fibers had gradually increased throughout the graft, and protruding serotonin fibers formed a network of varicose fibers in the host uveal tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576639 TI - Nephrotoxicity of cyclosporin A and contrast media. A comparison between diatrizoate and iohexol in rats. AB - Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 22 h or 8 days after intravenous injection of diatrizoate, iohexol or saline in 30 adult Wistar rats in which nephrotoxicity was induced by daily peroral administration of 25 mg/kg body weight cyclosporin A over a 14-day period. Another 10 rats which had the vehicle of the cyclosporin A solution (placebo) and saline injected intravenously served as controls. The effect of iohexol and saline on the albumin excretion was similar, whereas diatrizoate increased it significantly. Both contrast media caused significantly increased excretion of all three enzymes. The contrast media had no effect on the excretion of glucose and sodium. Except for the fact that the excretion of NAG was significantly higher following iohexol than following diatrizoate 24 to 46 h after injection no significant differences between the two media were found from 24 h after injection among the rats given cyclosporin A. No contrast medium related changes were found by light microscopy of the kidneys. Neither iohexol nor diatrizoate potentiate acute cyclosporin A nephrotoxicity. PMID- 2576640 TI - Lessons from past experience in cancer immunotherapy and their application to cancer and AIDS treatment and prophylaxis. AB - Passive immunotherapy which we attempted in 1957 using polyclonal antibodies from immunized donors aggravated tumor evolution: we suspected that blocking by Ig, tumor cell antigen epitopes which are necessary to enhance or even maintain the T lymphocyte effector role in anti-cancer immunity could be the reason for this tumor aggravation by "specific" antibodies. Today the very limited results of monoclonal antibodies in cancer treatment favors this hypothesis. The aggravation of HIV by (some) antibodies suggests that the same phenomenon may also happen in this condition. In 1957, on the other hand, we described the therapeutically beneficial cytostatic targetting effect of polyclonal antibodies, an effect which has often been quoted and widely confirmed. Does the reason for the poor results of monoclonal antibody targetting in tumor treatment reside in cancer antigen heterogeneity? This is what an experiment we conducted with Olsson on AkR leukemia indicated, suggesting that several monoclonals should be simultaneously combined for most patients, to be determined by the antigenic study not only of each tumor but of each localisation. We shifted our cancer immunotherapy approach to an adoptive form in 1959; a), after establishing partial and transient, then total and permanent allogeneic marrow graft and chimerism in man; b), after describing the graft versus leukemia (GvL) action of the graft versus host (GvH) effect in leukaemic mice; c), and the same phenomenon in humans. Our observations on human allogeneic grafted bone marrow GvH and GvL were statistically confirmed in 1979 by the Seattle group. In the 1970s we attempted to induce strong GvL with weak GvH by replacing allogeneic bone marrow graft by allogeneic lymphocyte transfusions without host conditioning. Remarkable results were registered in mice, and in patients with acute leukaemia--5 complete remissions out of 7 patients who developed moderate GvH, and only 3 out of 70 in those who did not develop GvH. As we now know that CD4-, CD8+ lymphocytes are not all MHCl restricted, we consider that the allogeneic CTL approach is worth trying as reinforcement treatment of (at least) severe hematopoietic malignancies. If it is indeed worthwhile in some severe neoplasias to include the adoptive form of immunotherapy in the multi-treatment program, the replacement of the patient's bone marrow by engrafted allogeneic stem cells has not been proven necessary, as the persistence in "ALL cured" chemotherapy patients of abnormally differentiated cells does not reduce the expectancy of cure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2576641 TI - Translation in a cell-free system, and in Xenopus oocytes, of mRNA which specify a cadmium-binding protein in Nereis diversicolor (Annelida, Polychaeta). AB - The presence in the marine worm Nereis diversicolor of a low molecular mass protein with the capacity to bind cadmium has been previously demonstrated. Poly(A)(+)-mRNA were extracted from coelomocytes of Nereis diversicolor and were translated either in vitro, using a rabbit reticulocyte lysate, or in vivo into Xenopus laevis oocytes. Analysis of synthesized polypeptides by enzyme-linked immunosorbent assay (ELISA) and by Western blotting, using a specific monoclonal anti-MP II antibody, showed that this metalloprotein was translated both in in vitro and in vivo translation systems, with an apparent molecular mass of 11-13 kDa. Two other products, with 26.5 and 28 kDa molecular mass, cross-reacted with the monoclonal anti-MP II antibodies. The present work confirms that coelomocytes are sites of important synthesis of MP II-mRNA. PMID- 2576642 TI - [An evaluation of the use of a cross leg flap in the early treatment of severe trauma of the foot. Report of 16 cases]. PMID- 2576643 TI - [Clinical application and improvement of an anterolateral thigh flap]. AB - Since 1984, the authors performed 15 anterolateral thigh cutaneous and myocutaneous flaps with vascular anastomosis and 1 island flap. Among them, 1 failed and 15 survived completely with satisfactory results. The sizes of the flaps used ranged from 6 x 7 cm to 11 x 20 cm. The flap seemed to have a constant vascular anatomy with a long pedicle and a large diameter, so that dissection of the flap can be accomplished easily. The quality of the flap was good and suitable for the repair of soft tissue defect of the hand and foot. In this paper, improvement of operative technique and two representative cases are presented. PMID- 2576644 TI - Synthesis of procaterol derivative having a piperidylmethanol group and its beta adrenoceptor stimulant activities. AB - A procaterol derivative (6) having a piperidylmethanol group was synthesized by the nucleophilic reaction of a 5-formylcarbostyril derivative with pyridyllithium, followed by selective catalytic reductions to afford the erythro isomer. Compound 6 showed non-selective beta-adrenoceptor agonist activities like those of l-isoproterenol in an in vivo assay using anesthetized dogs. PMID- 2576645 TI - [Central and peripheral alpha-agonist and antagonist drugs in pharmacology and therapy]. AB - Recent evidence has allowed to characterize the physiological role of adrenergic alfa-receptors either at the level of SNC or at peripheral level. Therefore it has been possible in this review to mention the mechanism of action, the therapeutical use of drugs acting on alfa-receptors and finally to suggest new applications of these drugs in therapeutics. PMID- 2576646 TI - [Familial forms of endocrine tumors of the pancreas. Apropos of 4 cases in the same family]. AB - Four cases of endocrine tumors of the pancreas and, more generally, of the diffuse endocrine system, are presented here. Included are all the data relative to the inherited character of the disease covering two generations. Two brothers had Zollinger-Ellison syndrome--one of them probably, the other one proven (first case recorded in France). Both patient's only sons are currently treated for endocrine tumor of the pancreas and Zollinger-Ellison syndrome, respectively. PMID- 2576647 TI - [2 cases of familial multiple endocrine neoplasia syndrome]. AB - Two cases of familial multiple endocrine neoplasia syndrome (MEN) are reported. Case 1. A 31-year-old woman began to have repeated attacks of coma in 1970. Blood examination showed fasting sugar as low as 2.05 mmol/L (37 mg/dl). Her disease was cured after the removal of two insulinomas in 1972. However, coma occurred again in 1982. Examination revealed the ratio of concentrations of serum insulin and sugar being more than 0.3. Another operation with removal of 19 insulinomas were performed in our hospital in 1985. After operation, the level of blood sugar returned to normal. Her father had suffered from Zollinger-Ellison Syndrome; the entire stomach and a part of pancreas were removed in 1967. So we examined her brother. His serum calcium level was 2.5-2.9 mmol/L (10.0-11.6 mg/dl) and plasma iPTH level 49.5-115.5 ng/L (normal value 21.4 +/- 7.7 ng/L n = 71). The high level of iPTH could not be suppressed by calcium load test. The total of two and a half of the remaining two parathyroid glands were removed. Pathology confirmed hyperplasia of parathyroid glands. The levels of serum calcium and iPTH returned to normal after operation. Case 2. A 25-year-old woman suffered from hypertension at the age of ten. Adrenal tumor with pheochromocytoma (2 x 2 x 1.5 cm3) was diagnosed and removed at that time. She complained of intermittent coma for 10 months and was thus admitted to our hospital in Nov. 1984. The level of blood sugar was 1.5-3.8 mmol/L (26-67 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576648 TI - The mouse Hox-1.4 gene: primary structure, evidence for promoter activity and expression during development. AB - This study reports the structure of the mouse homeobox-containing gene Hox-1.4 of the HOX-1 cluster, as well as its expression pattern during embryonic and fetal development. The overall structure of this gene includes two major exons, the second of which encodes the homeo-domain. The putative Hox-1.4 protein displays similarities with products of homologous genes located at the same relative positions in other HOX clusters. A fragment extending 360 base pairs (bp) upstream of a transcriptional start site was shown to be able to promote transcription in transfected cells. This fragment is GC-rich and contains binding sites for the Sp1 transcription factor. In situ hybridization studies revealed the Hox-1.4 expression pattern during development. As already reported for several other murine Hox genes, Hox-1.4 is expressed in the fetal central nervous system (CNS), in structures derived from somitic mesodermal condensations (sclerotomes, prevertebrae) as well as in several mesodermal components of various organs and structures such as lungs, gut, stomach, intestine and meso- and metanephros. This expression pattern is in good agreement with recent proposals concerning the involvement of such genes in the establishment of the vertebrate body plan as well as the relationship between the positions of these genes within their clusters and the anteroposterior restriction of their expression domains. PMID- 2576649 TI - Sodium butyrate enhances the activities of membranal enzymes and increases drug sensitivity in a cell line from ascitic fluid of an ovarian carcinoma patient. AB - The effect of sodium butyrate was examined on the growth and phenotypic expression of a cell line derived from the ascitic fluid of an untreated patient with ovarian carcinoma. The chemical inducer of differentiation, sodium butyrate, markedly enhances the activity of the membrane-bound glycoprotein enzymes, alkaline phosphatase and gamma-glutamyl transpeptidase. The alkaline phosphatase corresponds to placental Regan type. Sodium butyrate (1 mM) alone has only a small inhibitory effect on cell growth. However, it was shown to potentiate the anti-proliferative effect of Adriamycin and to render the cells sensitive to cis platinum. PMID- 2576650 TI - Failure to detect the P-glycoprotein multidrug resistant phenotype in cases of resistant childhood acute lymphocytic leukaemia. PMID- 2576651 TI - Long-range mapping in the research and diagnosis of genetic disease. AB - This paper reviews current genetic and molecular biological methods that may be used in the so-called "reverse genetics" approach. These methods are the mapping, isolation, and study of the chromosomal DNA containing a previously unidentified gene responsible for a genetic disease, beginning with its chromosomal localization. In principle, the reverse genetics methodology follows the same path for different diseases studied. An overall outline of the steps to be undertaken is given and discussed. Several stages are illustrated with reference to current research in the fields of Duchenne muscular dystrophy, Huntington's disease, and polycystic kidney disease. PMID- 2576652 TI - Organization of human class I homeobox genes. AB - We report the genomic organization of 20 human class I homeoboxes and the predicted primary sequence of the encoded homeodomains. These homeoboxes are clustered in four complex HOX loci on chromosomes 2, 7, 12, and 17. The homeoboxes of one HOX locus can be aligned to the homeoboxes of the other HOX loci so that corresponding homeodomains in all loci can share the maximal peptide sequence identity. This correspondence of individual homeoboxes in different chromosomal loci suggests the hypothesis of large-scale duplications of a single complex locus. The existence of an ancestral complex locus might have predated the divergence of vertebrates and invertebrates. PMID- 2576653 TI - Expression vectors for human adenosine deaminase gene therapy. AB - Somatic gene transfer offers a possible new approach for treatment of human genetic disease. Defects affecting blood-forming tissues are candidates for therapies involving transfer of genetic information into hematopoietic stem cells. Adenosine deaminase (ADA) deficiency is being used as a model disease for which gene transfer techniques can be developed and evaluated. We describe here the construction and testing of 20 retroviral vectors for their ability to transfer and express human ADA in vitro and in vivo via a mouse bone marrow transplantation model. After infection of primary bone marrow with one fo these vectors (p delta NN2ADA), human ADA was detected in 60-85% of spleen colonies at day 14 and maintained long term in the blood of fully reconstituted mice. This system offers the opportunity to assess methods for increasing efficiency of gene transfer, for regulation of expression of foreign genes in hematopoietic progenitors, and for long-term measurement of the stability of expression in these cells. PMID- 2576654 TI - Potential DNA methods for measuring the human heritable mutation rate. AB - Potential methods are reviewed for estimating human heritable mutation rates by comparing the DNA of parents of offspring. In the 4 years since the Alta Workshop on this subject, information has accumulated on several of the six methods detailed in that meeting. Some of the methods now appear to be infeasible, and all continue to be too inefficient for practical implementation. Newer DNA approaches are discussed, including several that could become practical enough for implementation. Finally, DNA-oriented methods using human sperm are considered as possible alternatives to the heritable approaches. PMID- 2576655 TI - Functionally different HTLV I-infected T cell lines with the same phenotype derived from a patient with melanoma. AB - Two autologous T cell lines infected with HTLV I are described. T cells from a patient with malignant melanoma were infected with HTLV I by co-culture with a HTLV I-producing T cell line, SLB I. Both T cell lines express identical phenotype (CD3+, CD4+, 4B4+, 2H4-) but they demonstrate marked differences in growth characteristics and function. One of these two lines, referred to as TFTx, established from the autologous tumor activated peripheral blood lymphocytes (PBL), grows in culture without any exogenous interleukin-2 (IL-2), secretes no detectable amount of IL-2 or gamma interferon (IFN) or tumor necrosis factor (TNF) alpha or beta. The other line (TFATx), established from a co-culture between the autologous PBL, lethally irradiated TFTx and the autologous melanoma cells TF-M, is IL-2-dependent for growth, secretes IFN gamma and TNF alpha and beta. TFTx exerts profound suppression of generation of cytotoxicity in the autologous PBL in co-culture with the autologous melanoma cells TF-M. In contrast, the TFATx enhances the cytotoxic response in similar co-culture. In addition to suppression of cytotoxic response, supernatant from TFTx suppresses the lectin-activated proliferation of PBL. In 4-h chromium release microcytotoxicity assays, neither line exhibits conventional characteristics of cytotoxic cells. Thus, phenotypically identical HTLV I-infected CD4+ T cell lines derived from the same individual exhibit opposite regulatory functions. PMID- 2576656 TI - Eye movement desensitization: a new treatment for post-traumatic stress disorder. AB - The use of saccadic eye movements for treating post-traumatic stress disorder is described. The procedure involves eliciting from clients sequences of large magnitude, rhythmic saccadic eye movements while holding in mind the most salient aspect of a traumatic memory. This results in (1) a lasting reduction of anxiety, (2) changes in the cognitive assessment of the memory, and (3) cessation of flashbacks, intrusive thoughts, and sleep disturbances. The procedure can be extremely effective in only one session, as indicated by a previous controlled study and a case history presented here. It does not require a hierarchical approach, as in desensitization, or the elicitation of disturbingly high levels of anxiety over a prolonged period of time, as in flooding. Some speculations are offered concerning the basis for the effectiveness of the procedure. PMID- 2576657 TI - Treatment of recurrent nightmares by the dream reorganization approach. AB - Dream reorganization is introduced as a new theoretical and treatment approach to the alleviation of recurrent nightmares, derived from the principles of the Seligman and Yellen (1987) theory of dream construction. The cognitive-behavioral dream reorganization treatment package consists of two treatment components. Systematic desensitization with coping self-statements is employed to alter the emotional episode by counterconditioning a relaxation response to anxiety-evoking nightmare content. Guided rehearsal of mastery endings to dream content hierarchy items is added to modify the secondary visual stimuli associated with recurrent nightmares. The dream reorganization approach is presented in the case of a 10 year-old male with a fear of sleeping alone due to recurrent nightmares. Following treatment, the client reported 100% reduction in nightmares and demonstrated 100% reduction in night time arrival in the parents' room. The present report provides a theoretical rationale for dream reorganization, and future directions for research in the treatment of recurrent nightmares. PMID- 2576658 TI - A new method for isolation of salivary neutrophils and determination of their functional activity. AB - The purposes of this study were to develop a new method for isolating salivary neutrophils (SPMNs), and to determine their functional activity. Studies of neutrophils in the oral cavity have been largely limited to crevicular PMNs, because of difficulties in obtaining viable SPMNs free of epithelial cells. A method to obtain SPMNs is presented. Donors performed rapid sequential rinsings by placing in their mouths 15 mL of Hanks' balanced salt solution [free of calcium or magnesium ions (HBSS-CMF)], which contained 0.1% gelatin, then swishing the solution for 30 s, and expectorating into a polypropylene receptacle containing 400 mL 4 degrees C HBSS-CMF. This sequence was repeated for 20 min. The collected solution was stirred for 10 min, the cells were washed, and the re suspended pellet was passed sequentially through a 20-microns and a 10-microns nylon mesh. The cells consisted of 97.7 +/- 1.7% SPMNs, only 2.3% epithelial cells, and were almost free of oral debris. The SPMNs were studied for CD11b expression, H2O2 production, and F-actin polymerization. SPMNs had significantly higher resting values for CD11b, H2O2 production, and F-actin polymerization compared with blood neutrophils (BPMNs). SPMNs responded to stimulation by chemotactic peptide or phorbol ester in a dose-dependent fashion, with levels of CD11b, H2O2, and F-actin comparable with BPMNs at optimal stimulant concentrations. The elevated resting levels of CD11b, H2O2, and F-actin for SPMNs were probably caused by exposure to gingival and oral bacteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576659 TI - Glutamine assimilation pathways in Neurospora crassa growing on glutamine as sole nitrogen and carbon source. AB - Neurospora crassa wild-type is almost unable to grow on glutamine as sole nitrogen and carbon source but a GDH-; GS +/- double mutant strain, lacking NADP dependent glutamate dehydrogenase and partially lacking glutamine synthetase did grow. Under these conditions, the double mutant had a higher chemical energy content than the wild-type. Enzyme assays and labelling experiments with glutamine indicated that in the double mutant glutamine was degraded to ammonium and to carbon skeletons by glutamate synthase, the catabolic (NADH-dependent) glutamate dehydrogenase and the glutamine transaminase-omega-amidase pathway. PMID- 2576660 TI - A genetic locus for the GltII-glutamate transport system in Escherichia coli. AB - Growth of Escherichia coli on glutamate as sole carbon source only occurs in strains carrying mutations that increase the expression of genes encoding glutamate transport systems. From an analysis of mutants able to grow on glutamate we have identified a genetic locus that when mutated elevates the expression of the GltII glutamate/aspartate transport system. The mutants exhibit increased sensitivity to the toxic aspartate analogues cysteate and DL-threo-beta hydroxyaspartate. Data from the analysis of mutants that are impaired in this transport activity are consistent with the presence of the structural gene for the transport system at the same genetic locus. The locus was mapped by P1 transduction to a region of the E. coli chromosome lying at approximately 92.5 min on the E. coli genetic map. PMID- 2576661 TI - Interstrain restriction fragment length polymorphism in the c-src correlates with Na,K cotransport and calcium content in hybrid rat erythrocytes. AB - Twenty-six F2 hybrids between spontaneously hypertensive (SHR) and normotensive control (WKY) rats [(SHR x WKY)F2] were segregated according to their c-src genotype into SS and WW homozygous groups, corresponding to SHR or WKY and a WS heterozygous group. The Na,K cotransport in erythrocytes in the WW group was equal to that of WKY and differed significantly from that of the WS and SS groups (the rate of Na,K cotransport in the latter groups was close to that of the SHR). The calcium content of the erythrocytes in the WW group was equal to that of the WKY, but lower than that of the WS and SS groups which, in turn, was significantly lower than that in the SHR, indicating polygenic control of the trait. We concluded that the c-src locus itself or some other loci inherited in conjunction with the c-src determines the increase in Na,K cotransport and in calcium content in erythrocytes of SHR. PMID- 2576662 TI - Blood pressure rather than humoral factors regulate arterial wall trophicity in rats with an aortocaval fistula. PMID- 2576663 TI - Reduction of blood pressure in obese hyperinsulinaemic hypertensive patients during somatostatin infusion. AB - Hypertension in the obese may be related to hyperinsulinaemia. To investigate this relationship further, we infused somatostatin (250 micrograms/h in 100 ml saline) or saline, single-blind and in a random order, for 10 h in seven obese hyperinsulinaemic hypertensive patients and in seven normo-insulinaemic hypertensive controls. Every 2 h, blood pressure, plasma insulin, glucose, sodium, potassium, renin, cortisol and aldosterone concentrations and the urinary sodium:creatinine ratio were determined. Two hours after the somatostatin infusion was started, mean arterial blood pressure was significantly reduced in the obese hyperinsulinaemic patients (from 128 +/- 11 to 114 +/- 11 mmHg, P less than 0.05) but not in the controls and this reduction persisted throughout the study. The somatostatin infusion reduced plasma insulin and increased plasma glucose similarly in both groups. Plasma sodium, potassium, renin, cortisol and aldosterone concentrations and the urinary sodium:creatinine ratio were unchanged after the somatostatin infusion. These results suggest that hyperinsulinaemia could help sustain the blood pressure rise in obesity. PMID- 2576664 TI - The cardiovascular effect of intracerebroventricular endothelin in rats. AB - To investigate the cardiovascular action of endothelin within the central nervous system, we studied the effect of intracerebroventricular endothelin in conscious Wistar rats. The endothelin increased blood pressure and the heart rate in a dose related way. The increase in mean blood pressure produced by 100 ng/kg of endothelin (45 +/- 6 mmHg, mean +/- s.e.m., n = 10) was much greater than that produced by the same amount of intravenous endothelin (4 +/- 1 mmHg, n = 7). Pretreatment with intravenous hexamethonium significantly attenuated the rise in blood pressure elicited by intracerebroventricular endothelin. Combined administration of hexamethonium and a vasopressin antagonist abolished the pressor response. These results indicate that centrally administered endothelin raises blood pressure through activation of the sympathetic nervous system and vasopressin. It is suggested that endothelin may play a role in the central regulation of cardiovascular function. PMID- 2576665 TI - Verapamil and nebivolol improve carotid artery distensibility in hypertensive patients. AB - The effects of verapamil (a calcium antagonist) and nebivolol (a novel, selective beta 1-adrenoceptor blocker) on carotid artery distensibility and cross-sectional compliance were studied non-invasively in hypertensive patients with the use of a high-resolution multigate pulsed Doppler system. Arm blood pressure measurements were made with an automated device (Dinamap). After a 4-week washout period, 19 patients (aged 21-73 years) with essential hypertension entered a double-blind randomized placebo-controlled crossover study with 120 mg verapamil or placebo three times a day for 4 weeks. After the administration of verapamil, carotid artery distensibility and cross-sectional compliance were significantly larger (P less than 0.05) than after placebo. Using the same protocol, 29 patients (aged 25 70 years) were given 5 mg nebivolol or placebo once a day for 4 weeks. After the administration of nebivolol, carotid artery distensibility and cross-sectional compliance were significantly larger (P less than 0.05) than after placebo. In both studies no significant differences in diameter and pulse pressure were found between placebo and verapamil or nebivolol. Blood pressure was decreased similarly with both verapamil and nebivolol. These results indicate that both verapamil and nebivolol favourably influence carotid artery distensibility and cross-sectional compliance of the common carotid artery, resulting in a better management of the systolic pressure pulse. The improved carotid artery distensibility may help to protect the patient against atherosclerotic complications of hypertension. PMID- 2576666 TI - Carvedilol and atenolol once daily in the treatment of hypertension. AB - Fifty milligrams of carvedilol and 100 mg atenolol were administered in a random order once a day for 2 months to 43 patients with mild to moderate hypertension, in a double-blind crossover study. Blood pressure, heart rate and peripheral blood flow parameters (n = 11) were recorded 2 and 24 h after the drug administration. Supine blood pressure was the same 2 h after both carvedilol and atenolol administration, but carvedilol caused a greater decrease in standing systolic blood pressure 2 h after the administration (P less than 0.05). The heart rate decreased less with carvedilol (P less than 0.01). There was no difference in the effects exerted by the two therapies on systolic blood pressure and the heart rate 24 h after drug administration, but the diastolic blood pressure was higher in patients given carvedilol (92 versus 88 mmHg; P less than 0.05). Forearm blood flow, forearm vascular resistance and calf blood flow did not change significantly with either of the therapies. In conclusion, 50 mg carvedilol once a day is an effective antihypertensive therapy, though its duration of action did not reach that of 100 mg atenolol once a day. Peripheral vasodilation was similar with both therapies. PMID- 2576667 TI - Comparison of a vasodilating beta-blocker and a cardioselective beta-blocker in long-term treatment of hypertension: a European multicentre study. AB - The therapeutic effectiveness and safety of indenolol, a vasodilating beta blocker with beta 2-agonism, was compared with that of atenolol, a cardioselective beta-blocker, in a 1-year double-blind trial. A total of 143 hypertensive patients (diastolic blood pressure 95-115 mmHg after 1 month of placebo) were randomly allocated to either atenolol, 50 mg/day, or indenolol, 60 mg/day. If the target diastolic blood pressure (less than or equal to 90 mmHg) was not reached after 1 month, the beta-blocker was doubled. If the target was still not reached, a diuretic was added after 2 months and doubled after 4 months. There was a higher overall responsiveness and monotherapy was more effective in the atenolol group, but at the lower dose indenolol was more effective than atenolol; however, no differences between drugs were significant. Although the drop-out rate was higher with indenolol, withdrawals due to side effects were similar in both groups. Indenolol was as effective and safe as atenolol in long-term antihypertensive therapy. PMID- 2576668 TI - Additional benefits of combining beta-blockade and renal vasodilation in the treatment of mild to moderate hypertension: Tertatolol International Multicentre Study results. PMID- 2576670 TI - Effect of urapidil on the performance of ischaemic myocardium in anaesthetized dogs. AB - The effect of urapidil on the ischaemic myocardium was studied in eight anaesthetized dogs. Stenosis of the left descending coronary artery reduced blood flow and systolic contraction of the post-stenotic myocardium by about 50%; the end-diastolic length of the post-stenotic myocardium and the end-diastolic pressure increased, while aortic pressure slightly decreased. Subsequent administration of urapidil (0.25 + 0.25 + 0.5 + 1.0 mg/kg intravenously) did not affect the systolic shortening and end-diastolic length of the myocardium supplied by the left circumflux coronary artery, while the stroke volume and the systolic shortening of the ischaemic myocardium increased. The latter was correlated with a decrease in the heart rate (r = -0.92), but not with the reduction in aortic pressure. Urapidil by itself does not impair the performance of the ischaemic myocardium, but might be beneficial in decreasing the heart rate or suppressing reflex tachycardia during reduction of the afterload. PMID- 2576669 TI - Plethysmographic effects of doxazosin in essential hypertensive patients. AB - In the treatment of hypertensive patients with peripheral vascular disease, alpha 1-adrenoceptor blockers may be considered first-choice drugs since they reduce the total peripheral resistance and do not decrease the plasma volume. As a preliminary step, we investigated the plethysmographic effects of doxazosin (1-8 mg for 6 weeks) on calf flow in 32 uncomplicated hypertensive patients. Despite the fall in sitting and standing blood pressure (from 163 +/- 18/101 +/- 6 to 147 +/- 19/94 +/- 8 mmHg and from 162 +/- 18/107 +/- 9 to 145 +/- 18/95 +/- 8 mmHg, respectively; both P less than 0.001) the calf flow was not decreased at rest and after ischaemia. Resting resistance was not significantly reduced (from 49.5 +/- 35 to 38.9 +/- 33 mmHg/100 ml per min) but its fall was significantly correlated with the fall in mean blood pressure (rs = 0.35, P less than 0.05). These findings confirm that doxazosin may be useful in the treatment of hypertension complicated by peripheral artery disease. PMID- 2576672 TI - Regression of left ventricular hypertrophy in hypertension with alpha-adrenergic blockade: physiological basis and therapeutic implications. AB - Left ventricular hypertrophy may be a serious consequence of chronic untreated hypertension since it may accentuate the risk of congestive heart failure, arrhythmias, coronary ischaemias and sudden death. Although haemodynamic factors may play a role in the genesis of left ventricular hypertrophy, certain neurohumoral mechanisms such as the adrenergic nervous system may induce left ventricular hypertrophy in patients with hypertension. There is considerable evidence to implicate adrenergic activation in the pathogenesis of left ventricular hypertrophy. Thus, adrenergic blockade may have a favourable impact on the course of left ventricular hypertrophy. Recent studies discussed in this paper have demonstrated that postsynaptic alpha-adrenergic blockers cause a significant reduction in the left ventricular mass. It is concluded that alpha adrenergic blockers can be added to the list of antihypertensive drugs which can cause regression of left ventricular hypertrophy in patients with hypertension. PMID- 2576671 TI - Diuretic and natriuretic properties of fenoldopam in chronic renal failure. AB - The effect of intravenously administered fenoldopam on diuresis and natriuresis was investigated in a group of 10 patients with advanced chronic renal failure. After an initial basal period of 1 h, a fenoldopam infusion was started and maintained for 12 h at rates varying between 0.025 and 0.1 microgram/kg per min. During the study, blood pressure was measured every 10 min and urine volume, natriuresis and creatinine clearance were measured hourly. Fenoldopam induced a significant increase in urine volume, natriuresis and creatinine clearance (P less than 0.05-0.001) accompanied by a small but significant drop in blood pressure (P less than 0.05-0.01). These results show that for advanced chronic renal failure, fenoldopam has diuretic and natriuretic properties that could be of clinical relevance. PMID- 2576673 TI - The role of glutathione in the induction of hepatic gamma-glutamyltransferase by phenobarbitone. AB - The effect of hepatic glutathione concentration on the induction of gamma glutamyltransferase (GGT) activity by phenobarbitone was investigated. A single dose of phenobarbitone 100 mg/kg weight was given to rats, and the concentration of hepatic glutathione and GGT activity were measured. The study results show a sharp drop of hepatic glutathione concentration within a few hours of injection. This drop precedes the increase in enzyme activity. PMID- 2576674 TI - [Evaluation of nursing information at a congress]. PMID- 2576675 TI - Effects of exercise, cold, and immobilization stresses on gamma glutamyltransferase activity in rat kidney. AB - Effects of acute and chronic stresses (exercise, cold, and immobilization) on gamma-glutamyltransferase (gamma GT) activity in the rat kidney were investigated. In the extramicrosomal fraction there were significant decreases in acute-exercised rats but significant increases in cold-adapted and immobilized rats. In the microsomal fraction, on the other hand, the gamma GT activity of acute-exercised rats increased definitely. The results suggest that different types of stresses have different effects on gamma GT activity in the rat kidney. PMID- 2576676 TI - [Surgical correction of cryptorchism]. PMID- 2576677 TI - [A device for postoperative autoanalgesia]. PMID- 2576678 TI - [Vistagan-Liquifilm in the treatment of simple glaucoma]. AB - Thirty patients (60 eyes) with bilateral open angle glaucoma in whom normalization of the IOP could not be obtained by a conservatory treatment with miotics are presented. In the period of 3 months they were given twice daily a 0.5% solution of Vistagan-Liquifilm, a compound blocking as well the beta 1 as the beta 2 receptors. After 2 weeks 76.7 p.c. of the treated eyes showed a normalization of the intraocular pressure and 23.3 p.c. an improvement. After 3 months the IOP was normalized in 73.3 p.c.; an improvement showed 26.7 p.c. of the eyes. The compound was well tolerated and did not cause any complications from the side of the respiratory or circulatory system. PMID- 2576679 TI - [Vasoactive intestinal polypeptide: a potential neurotransmitter]. AB - A review of current advances in anatomy, physiology and pharmacology of vasoactive intestinal polypeptide (VIP) is presented. VIP is a basic 28-aminoacid peptide of molecular weight 3300. Nerves immunoreactive to VIP are in the heart, lung, digestive and genitourinary tract, eye, skin, ovaries and thyroid gland. In the central nervous system VIP-ergic neurons are found primarily in telencephalic areas. Here, VIP provokes the excitation, vasodilatation and together with noradrenaline participates in the regulation of cortical energy metabolism. VIP ergic neurons are mainly present in afferent pathways of the spinal cord with higher density in the sacral segments. Anatomic distribution of VIP-ergic neurons suggests involvement in pain transmission and integration of the sacral autonomic reflex pathways. The biologic effects of VIP in periphery are the vasodilatation, relaxation of smooth muscle and influence on exocrine glands secretion. In the endocrine system VIP stimulates the secretion of different hormones (prolaction, growth hormone, oxytocin, vasopressin, ovarial and thyroid hormones). VIP-ergic innervation is changed in some organs during the diseases of those organs. Practical exploatation of this knowledge is limited at present because effective, non-polypeptide agonists and antagonists are not available yet. PMID- 2576680 TI - Clinical pharmacology of alpha2-agonist and beta-adrenergic blocker. AB - The pharmacological properties of centrally acting alpha2-receptor agonists such as clonidine suggest a potentially important role as ideal adjuvants for anesthesia since they produce sedation, analgesia anxiolysis, xerostomia and cardiovascular stability without respiratory depression, development of tolerance or addiction liability. Further clinical experience with this exciting development will undoubtedly establish the ultimate role and optimal use of alpha2 -receptor agonists in anesthetic practice. Beta-blockage can result in significant bradycardia, atrial ventricular conduction problems, bronchospasm and left ventricular contractile dysfunction. Thus, the use of long-acting beta blockers is of limited value in the perioperative period. Esmolol, because of its ultrashort action, cardioselective properties and titratability, has been shown to be safe and effective for the treatment of tachycardia and hypertension. Doses from 50 to 300 micrograms/kg/min for up to 7 hours in the perioperative period have been shown to cause no apparent cumulative effect. It has been used in the treatment of asthmatic patients with tachycardia and hypertension without significant increases in airway resistance. Studies using esmolol during general anesthesia have demonstrated no significant interaction with several anesthetic regimens. PMID- 2576681 TI - Effects of hormones on mitochondrial processes. PMID- 2576682 TI - [Acetyl-CoA-carboxylase: modification of ATP-binding site of the active center by 2',3'-dialdehyde derivative of ATP]. AB - The interaction of rat liver acetyl-CoA carboxylase with a 2',3'-dialdehyde derivative of ATP (oATP) has been studied. The degree of the enzyme inactivation has been found to depend on the oATP concentration and the incubation time. ATP was the only reaction substrate which provided protection from inactivation. Acetyl-CoA did not affect inactivation, while HCO3- accelerated the process. Ki values for oATP in the absence and the presence of HCO3- were 0.35 +/- 0.04 and 0.5 +/- 0.06 mM, and those of the modification constant (k) were 0.11 and 0.26 min-1, respectively. oATP completely inhibited the reaction of [14C]ADP in equilibrium ATP exchange, whereas produced actually no effect on [14C]acetyl-CoA equilibrium with malonyl-CoA exchange. Incorporation of about one equivalent of [3H]oATP per acetyl-CoA carboxylase subunit has been shown. No restoration of the modified enzyme activity has been observed in Tris or beta-mercaptoethanol containing buffers, and treatment with NaB[3H]4 has not led to 3H incorporation. The modification process involves elimination of the triphosphate chain of oATP. The results obtained indicate the affinity character of oATP-mediated modification of acetyl-CoA carboxylase. The reagent apparently interacts selectively with the epsilon-amino group of lysine in the ATP-binding site to form a morpholine-like structure. PMID- 2576683 TI - [Lack of evidence of genetic heterogeneity in a family with adult polycystic kidney (autosomal dominant) distinguished by early onset]. AB - Molecular hybridization experiments with the 3' HVR probe, located near the alpha globin gene, with DNAs coming from the different members of an unusual family with adult polycystic kidney disease, but with early manifestation, shows cosegregation between one of the marker's allele and the susceptibility gene of this disease; these results provide no evidence for a different gene locus responsible for the "adult-type" onset in this family. PMID- 2576684 TI - [Atracurium, vecuronium and pancuronium. Results of a polygraphic study]. AB - The Authors have studied three nondepolarizing muscle relaxants widely used: pancuronium v/s atracurium and vecuronium. The Train of Four was used to detect the magnitude of the neuromuscular blockade. The intubation follows 90 minutes after administration of the drugs and for each patient the Authors valued: 1) the T1 and TR values at intubation; 2) the onset-time; 3) the duration of neuromuscular blockade; 4) the recovery time. Furthermore, the degree of neuromuscular blockade was clinically checked both at the time of induction and at recovery. The results of the present study show, in accordance with the literature, that all three drugs tested are capable of obtaining complete muscle relaxation. Atracurium and vecuronium particularly allow an adequate intubation at the adopted doses (0.6 mg/kg and 0.1 mg/kg respectively) with a relatively short onset-time (medium values 136" in the group of atracurium and 146" in the group of vecuronium) and a restoration time faster than pancuronium. PMID- 2576686 TI - Neurotransmitters involved in the habenular control of raphe-hippocampal circuit. PMID- 2576685 TI - [The non-depolarizing myorelaxants in orotracheal intubation. A clinical comparison]. AB - The present study was designed to compare the rapidity of onset of neuromuscular blockade after administration of 5 different neuromuscular relaxants (succinylcholine, d-tubocurarine, pancuronium, atracurium and vecuronium) in 75 patients, randomly allocated in 5 treatment groups. The facilitation for endotracheal intubation was evaluated using a clinical score. The for onset relaxation was shorter when using succinylcholine. Among non-depolarizing relaxants an adequate facilitation for endotracheal intubation was observed, two minutes after administration of atracurium and vecuronium, while endotracheal intubation was difficult when using d-tubocuranine and pancuronium. PMID- 2576687 TI - Does chronic imipramine facilitate neurotransmission at dopamine-D1 receptor level? PMID- 2576688 TI - Binding affinity profile of somatostatin (SS-14) to rat CNS receptors. PMID- 2576689 TI - Contrasting quantitative alterations in CD4+ and CD8+ lymphocytes in HIV-infected African Americans compared with the Caucasian population. AB - Enumeration of circulating T lymphocytes is crucial in the investigation of AIDS and related conditions. The single best measure of disease progression and prognosis is the absolute number of helper/inducer T lymphocytes in the peripheral blood. Although the phenotypic identification of a particular subset reflects no direct information on the function of the population, the information provided by the analysis furnishes new insight regarding racial differences in the immune deficiency associated with AIDS. The severity of the HIV illness in the African American population, as reflected by a decrease in the absolute number of circulating CD4+ lymphocytes, was marked compared to the Caucasian population with AIDS. Consequently, the CD4/CD8 ratio was lower in the African American HIV+ population. A higher level of activated mononuclear lymphocytes and NK cells in this population may indicate active disease. The incidence of life threatening opportunistic infections such as PCP was greater in the adult/adolescent African Americans compared to Caucasians. In contrast, PGL was found more frequently in the Caucasian participants. Although the rate of HIV infection in the adult/adolescent African American population was not different from population estimates for the area under study, the incidence in the pediatric African American population was twice the population estimates for the race. This increased rate occurred in the parent-at-risk as well as in the hemophiliac group. PMID- 2576690 TI - [Root canal treatment and esthetic reconstruction in traumatology]. AB - The use of calcium hydroxide in the treatment of traumatic injuries are reviewed in this paper and demonstrated by some clinical cases. The necessity of a proper crown reconstruction is also emphasized as it is impossible to use posts in these treatments. PMID- 2576691 TI - [Calcium hydroxide in the treatment of traumatized teeth]. AB - Calcium hydroxide is used in the treatment of different traumatized teeth. New concepts about the effects of calcium hydroxide on vital pulps and immature non vital teeth are developed. Some clinical techniques and their results are described. PMID- 2576692 TI - [Endemic foci of hemorrhagic fever with renal syndrome in the North-Western region of the European part of the USSR]. AB - For the detection of specific antigens of hemorrhagic fever with renal syndrome (HFRS) virus, examinations were carried out covering 8.061 animals of 23 species trapped in the Murmansk, Archangelsk, Vologda, Novgorod, Pskov, Leningrad regions, the Komi ASSR, Estonian SSR, Latvian SSR, and Lithuanian SSR in 1984 1987. Different activity and variable species-specific composition of animal virus carriers in the north, south, and west of the north-western region were demonstrated. Circulation of HFRS virus of the first, "eastern", serotype has first been detected in the European USSR. PMID- 2576693 TI - [The use of immunoenzyme assay for detecting antigens of California group virus and Bunyamwera group virus (Bunyavirus, Bunyaviridae) in mosquito pools]. PMID- 2576694 TI - [Tubular lesions in the nephrotic syndrome]. AB - The problem of accompanying tubular lesions in nephrotic syndrome (NS) is not yet sufficiently clarified. The tubular changes were studied by the urine excretion of sensitive markers: beta 2-microglobulin (beta 2m), alaninaminopeptidase (AAP) and gammaglutamyltranspeptidase (gamma GTP). Beta 2m was determined by ELISA method and AAP and gamma GTP--electrophoretically. 75 patients were examined--37 patients with idiopathic nephrotic syndrome (INS), 27 patients with membranous glomerulonephritis (MGN), 11 patients with membranous-proliferative glomerulonephritis (MPGN). The most sensitive index AAP was elevated in the urine of 97,4% of the patients with nephrotic syndrome, beta 2m was elevated in 64,3% and gamma GTP--in 46,2% of the patients. There is a positive correlation between the excretion of APP and the quantity of proteinuria (r = 0,73, p less than 0,001). The comparison of the results of the patients with and without nephrotic syndrome established that in the patients with idiopathic nephrotic syndrome as well as in the patients with membranous glomerulonephritis the presence of nephrotic syndrome determines the higher excretion of AAP (p less than 0,02). The presence of nephrotic syndrome increases the frequency and the severity of the tubular impairment in glomerulonephritis. The tubular impairment is independent of the histologic type but is in positive correlation with the proteinuria. PMID- 2576696 TI - The P300 amplitude of the event-related brain potential indicates changes within a frame-of-reference. AB - The starting point of this study was the fact that investigations in the frame-of reference research were mostly performed on the behavioural level. The present study aimed at studying behaviour of P300 amplitude of the event-related brain potential in a frame-of-reference investigation. Ten healthy volunteers participated in the investigation. Test material consisted of horizontal bars of different lengths presented successively on a screen. Each bar (serial stimulus) was preceded by a prestimulus (anchor) of constant length. Each serial stimulus was to be evaluated according to a 9 step rating scale. There were no significant differences in the overt length judgements of the serial stimuli depending on the 3 different anchor lengths. However, the mean P300 amplitude increased with growing dissimilarity between the length of the anchor and serial stimulus length. Thus, it is assumed that the adaptation level on the internal dimension of stimulus length, which was assumed to be influenced by the anchor stimuli, led to the different behaviour of P300 amplitude. PMID- 2576695 TI - [The sociobiological ideas of Arthur Schopenhauer]. AB - Starting from the basic ideas of sociobiology we prove that Schopenhauer, in his "Metaphysics of Sexual Love", has to pass for a precursor of sociobiological thinking. Several consequences of this parallel are discussed: The quest for strategic principles of organismic growth and evolution as a positive characteristic of both approaches--the hypothesis of a dominant genetic determination of human behaviour as an outcome of a typical bourgeois view of mankind connecting Schopenhauer and sociobiologists--the necessity of taking into consideration biological predispositions of flexible (learned) behaviour as elements of sociobiological models enjoying the same rights as genetical ones- the utility of Schopenhauer's natural philosophy for the purpose of complementing historical knowledge of many disciplines (also psychology). PMID- 2576698 TI - [The rheumatic elbow joint]. PMID- 2576697 TI - Effects of vitamin C long-term loading on the serum gamma-glutamyltranspeptidase activity in human subjects. AB - In an attempt to assess dietary effects on the serum enzyme activity of long-term vitamin C supplementation, the serum gamma-GTP(1) fraction was studied in five healthy men. In this study, they were maintained on ordinary meals for the initial one year and the last 7 months of the 43 month experimental period, and on ordinary meals with 1 g/day of vitamin C powder for the intermediate 2 years. The serum gamma-GTP(1) fraction during the first year (ordinary meals alone) was higher than that for the second or third year (ordinary meals with addition of vitamin C). The decrease after vitamin C supplementation was statistically significant. The serum vitamin C concentration tended to rise in winter. Vitamin C supplementation at 1 g/day raised the concentrations up to 1.6 mg/dl on average, where the serum was practically saturated with vitamin C. PMID- 2576699 TI - [The elbow joint--a historical presentation on the occasion of the meeting of the Society of Rheumatologic Orthopedics in Bad Abbach 1988]. PMID- 2576700 TI - [Controlled partial weight bearing--a concept for shoe construction]. PMID- 2576702 TI - [Functional anatomy of the elbow joint]. PMID- 2576701 TI - [The Society of Rheumatologic Orthopedics documentation exemplified by elbow joint synovectomy]. PMID- 2576703 TI - [Forms of destruction of the head of the radius in chronic polyarthritis]. PMID- 2576704 TI - [The value of ultrasound examination of the rheumatoid elbow joint]. PMID- 2576705 TI - [Possibilities for the use of elbow joint arthroscopy in rheumatology]. PMID- 2576706 TI - [Radiosynoviorthesis of the elbow joint]. PMID- 2576708 TI - [Resection-interposition arthroplasty of the elbow joint in chronic polyarthritis -indications and results]. PMID- 2576707 TI - [Differential indications, surgical technics and follow-up treatment concepts of elbow joint surgery in polyarthritis]. PMID- 2576709 TI - [Results of synovectomy of the elbow joint in chronic polyarthritis]. PMID- 2576711 TI - [Early results with the Souter/Strathclyde elbow joint prosthesis in patients with chronic polyarthritis (rheumatoid arthritis)]. PMID- 2576710 TI - [The effect of resection of the head of the radius on the results of synovectomy of the elbow joint in chronic polyarthritis]. PMID- 2576712 TI - [Long-term results with the GSB III elbow arthroplasty]. PMID- 2576713 TI - [Shoulder joint arthroplasty--joint replacement]. PMID- 2576714 TI - [Extension of the "dorsal wrist stabilization" by radio-ulnar arthrodeses in chronic polyarthritis]. PMID- 2576715 TI - [Plate arthrodesis with homologous bone transplant in the extremely destroyed wrist joint in the polyarthritis patient--technical contribution]. PMID- 2576716 TI - [Use of opiates in obstetric epidural analgesia]. PMID- 2576717 TI - [Rapid sequence muscular relaxation: vecuronium versus succinylcholine]. AB - Onset times and conditions of endotracheal intubation were compared in 340 patients. They were all classified ASA I or II and free from any condition which might interfere with the pharmacokinetics or pharmacodynamics of muscle relaxants. The patients were randomly assigned to 4 groups where different muscle relaxation techniques with vecuronium were used: "priming" group (n = 150, 10 micrograms.kg-1 followed by 100 micrograms.kg-1 4 min later), "high dose" group (n = 70, 250 micrograms.kg-1), "control" group (n = 60, 100 micrograms.kg-1) and "succinylcholine" group (n = 60, 1 mg.kg-1). All anaesthetic conditions were otherwise similar. Electromyographic monitoring of the hypothenar muscles displayed no impairment in the reaction to a train-of-four stimulus during the pre-relaxation period (4 min) in the "priming" group. No incident was observed in these patients. Ten % of control response were obtained in 61, 86, 135 and 210 s respectively, whereas maximum muscle blockade was obtained in 97, 174, 314 and 74 s respectively. Intubation scoring showed that optimum conditions were obtained when muscle responses were almost fully abolished. These data are in disagreement with those reports on the priming technique where intubation is carried out 60 s after administration of the relaxing dose. PMID- 2576718 TI - [Use of epidural and intrathecal opiates in obstetrics]. AB - The discovery of opiate receptors and naturally occurring opiate-like substances in the central nervous system started a new era in pain control. Epidural and spinal opiates have been increasingly used since 1979. However, applying these analgesic techniques in obstetrics has been criticized because of possible side effects on the mother and foetus. In this literature survey, their advantages and disadvantages are analyzed. Maternal side-effects include pruritus, nausea, urinary retention, and, most of all, respiratory depression. As a general rule, these side-effects are greater with the intrathecal route, high doses, and the use of morphine. The effects on the course of labour are small, and neonatal status is not altered. Spinal and epidural opiates are efficient analgesic techniques for labour and caesarean section. They provide a dose-related, but not surgical, analgesia. Currently, there is a great deal of interest in mixtures of a diluted local anaesthetic agent and a lipophilic drug for use during labour or caesarean section. An opiate alone may not consistently provide satisfactory analgesia during labour, and it cannot be recommended for routine use, except for patients in whom the cardiovascular effects of routine regional anaesthesia are to be avoided. The choice of a lipid-soluble opiate like fentanyl is safe. However, when considering new drugs, great care must be taken to avoid unforeseen problems. A good knowledge of the problem and a cautious approach combined with careful monitoring of the respiratory rate and adequacy of ventilation are the keys to the safe use of spinal and epidural opiates. PMID- 2576719 TI - [Entomological results of the malaria program of the Pasteur Institute in the Malagasy Highland Plateaux in 1987-1988]. AB - An entomological survey carried out between october 1987 and july 1988 in Manarintsoa, a village 30 Km West of Antananarivo, shows that An. gambiae s.l. and An. funestus are both vectors of malaria. The sporozoite rate was estimated at 0.71%, and the annual risk about 2 infectious bites per person. In all, more than 16,000 mosquitoes, belonging to at least 15 species, were caught over a period of 294 nights. PMID- 2576720 TI - [A comparative study of the effectiveness of regulatory peptides in acute experimental pancreatitis]. AB - The effect of regulatory peptides on the functional activity of pancreatic cells and phagocytic cells of reticuloendothelial system were determined in intact dogs against the background of acute experimental pancreatitis. Assessment of the efficacy of regulatory peptides was made with the aid of scintigraphic studies in gamma chamber using for this purpose colloid 198Au and 75Se-methionine. It was established that introduction of regulatory peptides to dogs leads to inhibition of capture of labeled methionine by pancreatocytes, practically not influencing the elimination of colloid gold from circulation. PMID- 2576721 TI - [The Children's Rights convention]. AB - A Convention project about Children Rights will be soon submitted for ratification to all member states of the United Nations. It is the continuation of several anterior declarations which principles it recalls in its preamble: fundamental responsibility of the family for the care and the protection of the child, necessity of a social and juridical child protection depending on the state, vital role of an international cooperation so that the children rights will become a reality. After having largely analysed the needs of the child in the world, the project proposes the creation, inside the United Nations, of a Committee of the Children Rights with 10 members. Though a progress in comparison with the anterior declarations, many articles won't be easy to apply immediately: furthermore, the problems differ from the industrialized countries to the most disfavored countries. Nevertheless the Convention constitutes an engagement and a line of conduct for the future. PMID- 2576722 TI - [Nature, origin and role of fatty acids of the nervous system: an essential fatty acid, an alpha-linolenic acid, changing the structure and the cerebral function]. AB - Saturated and monounsaturated fatty acids are synthetized in cytosol, endoplasmic reticulum and mitochondria. Their mechanisms of synthesis and fate are different according to the organelle. For some of them, a nutritional origin is not excluded. Minimum dietary linoleic and alpha-linolenic acid to ensure normal brain structure and function are respectively 2.4% and 0.4% of the calories. Alpha-linolenic acid deficiency alters membrane composition and fluidity, changes the fluidizing effect of ethanol, reduces some enzymatic activities (ATP ase, 5' nucleotidase), diminishes the efficiency of the blood-brain barrier, affects electroretinogram, reduces learning capacities and makes the animals more fragile in the presence of neurotoxins. Very long polyunsaturated chains, which could be the essential fatty acids for the brain, must be considered at the level of nutrition, pharmacology and toxicology (alteration of structures and peroxidations). PMID- 2576723 TI - [Fetal curarization during exchange transfusions carried out in utero for the treatment of severe rhesus isoimmunization. Clinical study of vecuronium bromide. Preliminary results]. PMID- 2576724 TI - Cytotoxicity of cholesterol oxidase to cells of hypercholesterolemic guinea pigs. AB - 1. A high cholesterol diet caused guinea pig erythrocytes to become sensitive to lysis by cholesterol oxidase (CO), a protein not hemolytic to normal cells. 2. Lysis was associated with conversion of membrane cholesterol to its oxidation product (delta-4-cholesten-3-one). 3. Intravenous injection of CO to hypercholesterolemic guinea pigs produced a reduction in serum cholesterol, but was not lethal as it was in rabbits. 4. Homogenized spleen, liver and kidney from the hyperlipidemic animals were sensitive to in vitro cholesterol oxidation while tissues from non-lipemic animals were resistant to modification. PMID- 2576725 TI - Cisplatin: nephrotoxic action in vertebrates and its prevention. AB - 1. The kidney of frog and black sculpin appeared to be much less sensitive to the toxic action of CP in comparison with rat and pigeon. 2. The impairment of renal function after CP administration resulted in increased serum urea in rat, uric acid in pigeon and magnesium in black sculpin. 3. Kidney swelling is important feature of CP nephrotoxicity in rat and pigeon but not in frog and fish. 4. Pretreatment with choline chloride, PAH, furosemide and ethacrynic acid reduced the nephrotoxic action of CP in rat but did not prevent the accumulation of platinum in renal tissue which appeared to be a function of the dose injected to investigated animals. PMID- 2576726 TI - Effects of AF64A on cholinergic neurotransmission in the sixth abdominal ganglion of the cockroach. AB - 1. The effects of ethylcholine mustard aziridinium ion (AF64A) on the cholinergic neurotransmission in the sixth abdominal ganglion of the cockroach were studied electrophysiologically and morphologically. 2. The pre- and post-synaptic compound action potentials (CAPs) elicited via electrical stimulation of the presynaptic fibers were recorded extracellularly. 3. The amplitude of both CAPs was depressed by AF64A (50-400 microM) in a concentration- and time-dependent manner. 4. At a high concentration, they were abolished but 100 microM of carbachol still evoked the postsynaptic event. 5. Electron microscopic observation of AF64A-treated ganglia showed that nerve terminals containing small lucent vesicles could not be observed but those containing dense core or large granular vesicles changed only slightly in shape. 6. These results suggest that AF64A is selectively neurotoxic for the presynaptic cholinergic neurons in the sixth abdominal ganglion of the cockroach. PMID- 2576727 TI - Thermal salivation in rats, anesthetized with barbiturates, chloralose, urethane and ketamine. AB - 1. The relationship between thermal salivation (TS) and thermoregulation was studied in anesthetized rats. 2. Of the 6 anesthetics used, ketamine-anesthetized rats secreted the largest amount of saliva. Salivation, however, was thermal and not induced by ketamine itself. 3. Ketamine-anesthetized rats readily secreted saliva at core temperatures less than 40 degrees C but TS was remarkably enhanced by hyperthermia of 40-42.5 degrees C. 4. The equilibrium phase in the triphasic heat response of core temperature was a consequence of equilibrium between heat gain and heat loss by salivation. PMID- 2576728 TI - Temperature and adrenoceptors in the frog heart. AB - 1. Cardiac adrenergic receptors in a frog, Rana tigrina, were examined in winter and summer months using isolated atria preparation maintained at 24 degrees, 14 degrees and 6 degrees C. Treatments included an examination of the atrial responses to selective alpha and beta adrenergic agonists (phenylephrine and isoproterenol respectively) and antagonists (phentolamine and propranolol). 2. Basal atrial beating rates differed between summer and winter months and increased with temperature. 3. Phenylephrine produced dose-dependent increases in the atrial beating rate and tension in the winter frogs only at 6 degrees C. These increases were blunted by phentolamine. 4. Isoproterenol produced positive chronotropic effects of 14 degrees and 24 degrees C but not at 6 degrees C in both summer and winter frogs; these effects were abolished by propranolol. Further, at 6 degrees C, the contractile response of the atrial tissue to isoproterenol was very sensitive. 5. Data suggests that the alpha adrenoceptor might be physiologically important to the frog in the low temperature environment of the cold season, during which period the cardiac beta adrenergic activity would be minimal or even absent. PMID- 2576729 TI - Studies on the properties of muscarinic cholinergic receptor sites in bovine pineal gland. AB - 1. Using the tritiated muscarinic receptor antagonist, quinuclidinyl benzilate ([3H]QNB) as a ligand, muscarinic cholinergic receptors have been identified and characterized in the pineal glands of cow and swamp buffalo. 2. At 25 degrees C, the specific binding reached equilibrium within 60 min and remained constant for an additional two hours. Furthermore, the specific binding was saturable, reversible and tissue dependent in nature. 3. The kinetic analyses of muscarinic cholinergic receptor sites revealed KD values of 0.423 +/- 0.01 nM and 0.218 +/- 0.01 nM, and Bmax values of 69.75 +/- 20.91 fmol/mg protein and 74.19 +/- 32.73 fmol/mg protein for the cow's- and the swamp buffalo's pineal glands, respectively. 4. The presence of muscarinic cholinergic receptor sites originating from cholinergic innervation of the pineal gland is suggested. PMID- 2576730 TI - Relaxing action of a holothurian toxin on mammalian smooth muscle. AB - 1. The crude epidermal mucous secretion produced by the sea cucumber Holothuria mexicana Ludwig inhibits the tonus and spontaneous mechanical activity of rabbit ileum at concentrations of 0.1 mg/ml and higher. 2. This effect, similar to that of epinephrine, is attributed to a compound referred to as mucotoxin (MuTX). 3. MuTX also relaxes strips of the rabbit aorta contracted by 10(-8) M norepinephrine and exerts a similar, less marked, effect on the same strips contracted in high potassium solutions. 4. These observations suggest that the relaxing effect of MuTX on mammalian smooth muscle is not mediated by an adrenergic mechanism. PMID- 2576731 TI - Effect of DDE on ionic and fluid movement in rat colon in vitro. AB - 1. The effect of DDE on ionic (Na+ and K+) and fluid movement was studied in rat colon in vitro. 2. DDE (10(-7) M) increased net K+ secretion while inhibited the net flux of Na+ and fluid movement inducing net secretion. 3. DDE added before or after aldosterone caused an inhibition on the net influx of Na+ and fluid movement and potassium secretion. 4. DDE also inhibited (Na+ and K+)-ATPase from the same tissue suggesting that the inhibition of DDE is due to an action of this organochlorine compound on the sodium pump. PMID- 2576732 TI - Serotonin receptors for chloride secretion in hen colon. AB - 1. The effect of serotonin on chloride secretion in hen colon was studied under short circuit conditions. 2. Serotonin added to the serosal side induced a short lived peak increase in Cl(-)-secretion (6.2 +/- 1.0 mumole.cm-2.h-1), in short circuit current (5.4 +/- 0.7 mumole.cm-2.h-1) and in cord conductance (8.1 +/- 0.7 mS.cm-2) with an apparent EC50 around 8 microM, and a more prolonged rise in chloride secretion of around 3.0 mumole.cm-2.h-1. 3. The short circuit current is a reasonable measure of net chloride secretion at the peak. 4. Several specific and non-specific serotonin receptor antagonists were studied for their influence on the serotonin induced peak response in short circuit current and cord conductance. 5. These antagonists covered the whole range of currently defined serotonin receptor types and subtypes: 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2, and 5-HT3. 6. Adrenergic, cholinergic and histaminergic receptor antagonists were also tested for an interaction at the serotonin receptor involved in Ca(-) secretion. 7. None of the antagonists had any influence on the serotonin response in short circuit current or cord conductance. PMID- 2576733 TI - Comparison of the pharmacological profiles of adrenergic drugs (including BRL agonists) at [3H]prazosin and [3H]CGP-12177 binding sites in brown adipose tissue. AB - 1. In order to determine the selectivity of classical and novel adrenergic agents for alpha 1- and beta-adrenergic receptors in brown adipose tissue, the ability of these agents to compete for binding sites labelled with [3H]prazosin and [3H]CGP-12177, respectively, was investigated. 2. The beta-antagonist propranolol, known to inhibit norepinephrine-induced respiration in micromolar concentrations, bound to the [3H]CGP-12177 site with nanomolar affinity. 3. Among agonists, only isoprenaline showed high selectivity for beta-receptors, and only oxymetazoline for alpha 1-receptors. 4. Unexpectedly, the novel thermogenic agonists (BRL-agonists), shown to be potent and selective stimulators of brown fat thermogenesis, were unselective and bound only with low affinity to the [3H]CGP-12177 binding sites. 5. These results suggest that the beta-adrenergic binding site in brown adipose tissue identified here with [3H]CGP-12177 may not be the one (or not the only one) coupled to thermogenesis. PMID- 2576734 TI - Inotropic response elicited by nematocyst contents of Hydra oligactis (Coelenterata: Hydrozoa). AB - 1. Intact, isolated nematocysts from the non-toxic, freshwater coelenterate Hydra oligactis contain soluble material(s) capable of producing a sustained increase in the rate of developed force in the vertebrate myocardium. 2. The positive inotropic effects of this material(s) appear grossly comparable to those described for Anthopleurin-A (AP-A) and Toxin II (ATX-II) from sea anemones. 3. The effects of the nematocyst material are distinct from those of known vasoactive peptides reported to occur in Hydra. PMID- 2576736 TI - Binding of [3H] muscimol to the retina of rabbit and turtle. AB - 1. We studied the binding of [3H]muscimol to membrane preparations of the retina of rabbit (Lepus cuniculus) and turtle (Pseudemys scripta elegans). 2. In both species, [3H]muscimol binding was maximal at 0 degrees C and decreased with increasing temperature, it was saturable, protein concentration dependent and specific. Muscimol, GABA and bicuculline were the most effective displacers, whereas baclofen and diaminobutyric acid were ineffective. 3. In the turtle retina, Scatchard analysis indicated the presence of a single site with a KD of 20.81 nM, and a Bmax of 3.620 pmol/mg prot. 4. In the rabbit, a single site could be identified in the nanomolar concentration range (KD of 12.8 nM, Bmax of 1.327). A study of the association rate of [3H]muscimol binding revealed a faster kinetics in turtle, as compared to rabbit. PMID- 2576735 TI - Binding of [3H]batrachotoxinin A-20-alpha-benzoate to a high affinity site associated with house fly head membranes. AB - 1. [3H]Batrachotoxinin A-20-alpha-benzoate (BTX-B), a radioligand that labels the alkaloid activator recognition site of the voltage-sensitive sodium channel, was bound specifically to high affinity, saturable sites in a subcellular preparation from house fly (Musca domestica L.) heads that was shown previously to contain binding sites for other sodium channel-directed ligands. 2. Specific binding of [3H]BTX-B was observed in the presence of 140 mM sodium or potassium and was inhibited by choline ion. 3. Saturating concentrations of scorpion (Leiurus quinquestriatus) venom stimulated the specific binding of [3H]BTX-B four-fold, increasing the proportion of specific binding of 10 nM [3H]BTX-B from less than 15% to 40%. Equilibrium dissociation studies in the presence of scorpion venom gave an equilibrium dissociation constant (KD) for [3H]BTX-B of 80 nM and a maximal binding capacity (Bmax) of 1.5 pmol/mg protein. 4. Parallel experiments in the absence of venom gave a KD value of 140 nM and a Bmax of 1.3 pmol/mg protein, indicating that scorpion venom stimulated [3H]BTX-B binding by increasing the affinity of this site approximately two-fold. 5. The specific binding of [3H]BTX-B was inhibited by the sodium channel activators aconitine and batrachotoxin and, to a lesser extent, by the anticonvulsant diphenylhydantoin. However, several other sodium channel-directed neurotoxins known to exert allosteric effects on the binding of [3H]BTX-B to mammalian brain preparations did not affect the binding of [3H]BTX-B to house fly head membranes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576737 TI - Brain cholinergic enzymes and cortical EEG activity in young and old rats. AB - 1. Cholinergic enzymes (ChAT, AChE) in different areas of the brain and cortical electroencephalography (EEG) activity were investigated in young and old rats. 2. In old rats, ChAT activity was low in the striatum, but high in the amygdala. Compared to young rats, ChAT activity in old rats was unchanged in the frontal, parietal/occipital and entorhinal cortex as well as in the hypothalamus, midbrain, hippocampus and brain stem. 3. AChE activity in old rats was lower than in young animals in the parietal/occipital cortex, hippocampus, striatum and brainstem. In other areas of the brain AChE activity was unchanged. 4. In old rats the peak frequency (Fp) of cortical EEG activity (mobility-related) was significantly lower than in young animals, both frontally and occipitally. The power of 5-10 Hz frequency band was markedly lower than in young rats. During immobility, the power of the 1.5-3 Hz and 3-5 Hz bands was lower in the frontal cortex of old rats. The power of 3-5 Hz, 5-10 Hz and 10-20 Hz bands was lower in the occipital cortex of old rats. In all of the old rats, but not in any of the young ones, symmetric high voltage activity was observed in the frontal pole of the cortex. 5. These results suggest that the age-related decrease of higher frequencies of cortical EEG activity may be related to the decrease of AChE activity in the parietal/occipital cortex. This decrease in AChE may reflect degeneration of the cholinergic synapses. PMID- 2576738 TI - Sensitivity to dicholines of membranes from vertebrate and invertebrate muscles. AB - 1. The depolarizing effectiveness of azelainylcholine (AzCh, a 7-C-chain dicholine) is about 10 times higher than that of succinylcholine (SCh, a 2-C chain dicholine) in skeletal muscles of chick, frog and fish, and in body muscles of the earthworm. 2. In the chicken anterior latissimus dorsi (ALD) muscle, AzCh is about 100 times more effective than SCh. 3. In contrast to that in mammalian muscles, the AzCh-SCh sensitivity difference is not increased by denervation in frog muscles. 4. d-Tubocurarine is equally effective in the ALD and in other chicken muscles; its effectiveness is not decreased by denervation in frog muscles. 5. Cells containing muscarinic acetylcholine receptors are weakly sensitive to dicholines or not at all. PMID- 2576739 TI - Ketamine-induced tongue protrusions in rats. AB - 1. The purpose of this study was to demonstrate that ketamine anesthesia (100 mg/kg) induces tongue protrusions (P) in addition to retrusions (R) and swallows (S) in adult rats. 2. These linguo-pharyngeal events occur alone or combined in various sequential patterns. 3. The SPR sequence is not the predominant pattern in all preparations suggesting profound disruption of physiological linkages by ketamine. 4. Haloperidol administration suppresses these events for 1-120 min depending on the dose (0.75-2.5 mg/kg). 5. Swallows are the least vulnerable to haloperidol. 6. This and previous findings provide further evidence that ketamine induced linguo-pharyngeal activity can serve as a model for acute or tardive dyskinesia better than stereotypies. PMID- 2576740 TI - Modulation of swimming activity in the medicinal leech by serotonin and octopamine. AB - 1. The monoamines serotonin (5-HT) and octopamine (OA) enhance the expression of swimming activity in the medicinal leech (Willard, 1981; Belanger and Orchard, 1988). We explored further the effects of these monoamines and related agents on swimming activity observed in isolated leech nerve cords. 2. We confirmed that swimming activity is induced reversibly following exposure of the nerve cord to 5 HT (50 microM); the half-maximal rate of swimming activity develops in about 15 min. Swimming activity returns to control levels about 30 min after drug washout. 3. Swim-induction by 5-HT is blocked by the presence of 10 microM cyproheptadine (a 5-HT antagonist). 4. Although apparently less effective than 5-HT, OA application to nerve cords also induced swimming activity. 5. Depletion of endogenous amines from nerve cords by acute exposure to reserpine (10-150 microM) blocked stimulus-evoked swimming activity within 4 hr. 6. Subsequent application of 5-HT (50 microM) or OA (100 microM) reinstated stimulus-evoked swimming and induced repeated episodes of non-triggered swimming activity. 7. Application of cAMP and cAMP analogs, as well as phosphodiesterase inhibitors (theophylline and IBMX), mimicked the effects of the monoamines, suggesting that 5-HT and OA may activate swimming activity by increasing neuronal cAMP. 8. We obtained episodes of swim-like activity from individual, isolated ganglia exposed to 5-HT or OA. Such episodes were usually brief, with variable cycle period. 9. We conclude that individual nerve cord ganglia contain the complete neuronal circuitry required to generate the rudiments of swimming activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576741 TI - Influence of ormetoprim on the bioavailability, distribution, and pharmacokinetics of sulfadimethoxine in rainbow trout (Oncorhynchus mykiss). AB - 1. Half lives of distribution and elimination phases of 14C-sulfadimethoxine following i.v. dosing of sulfadimethoxine/ormetoprim (SDM/OMP, 42/8 mg/kg) were 0.4 and 16.1 hr respectively. The apparent volume of distribution was 503.9 ml/kg. 2. In vitro plasma protein binding of 14C-SDM was not altered by increasing concentrations of unlabeled OMP. Similarly, binding of 14C-OMP was not altered by SDM. 3. Peak plasma concentrations of 14C-SDM following oral administration of SDM/OMP were observed at 20 hr with an apparent bioavailability of 38%. 4. Oral dispositional studies revealed the highest concentrations of 14C SDM in bile, intestine, liver and fat. 5. Parent SDM and N-acetylated SDM were detected in plasma from i.v. and orally dosed animals. 6. The pharmacokinetics and distribution of 14C-SDM were not influenced by OMP co-administration. PMID- 2576742 TI - Inhibition by taurine of Na(+)-Ca2+ exchange in sarcolemmal membrane vesicles from bovine and guinea pig hearts. AB - 1. Taurine, but not GABA, beta-alanine and glycine, inhibited Na(+)-dependent Ca2+ uptake in bovine cardiac sarcolemmal membrane vesicles in a dose-dependent manner. 2. The inhibition of Na(+)-dependent Ca2+ uptake was noncompetitive with respect to Ca2+ concentration. 3. The inhibitory effect of taurine on the exchange was also observed in cardiac sarcolemmal vesicles prepared from guinea pig, but not from rat. 4. Taurine did not affect Na(+)-dependent Ca2+ efflux nor ATP-dependent Ca2+ uptake in the bovine cardiac membranes. PMID- 2576743 TI - Effects of emulsified perfluorochemicals on liver cytochromes P-450 in rats. AB - 1. The effects of intravenous (i.v.) injection of various perfluorochemical (PFC) emulsions or different fractions of the non-ionic poloxamer surfactant, Pluronic F-68, have been studied separately in male and female rats. 2. Injection of 10 ml/kg body wt of either Fluosol-DA 20% (F-DA) or a novel perfluorodecalin emulsion containing a C-16 oil additive in male rats increased liver weight up to 7 days later; no corresponding effect occurred in response to injection of Oxypherol (FC-43). 3. Liver weight was also increased in female rats at 72 hr after injection of the novel emulsion but this was less pronounced than in males; liver weight in female rats was unchanged in response to injection of either F-DA or FC-43. 4. Mean liver microsomal cytochromes P-450 concentrations in male rats were increased 2-3 fold at 72 hr after injection of either F-DA or the novel emulsion with a less pronounced increase also seen at 7 days in animals receiving the novel emulsion. No significant alterations in cytochrome concentration occurred in response to injection of FC-43 or either commercial grade or purified pluronic solution. 5. Liver cytochromes P-450 concentrations in female rats were unaffected by any of the experimental treatments. 6. These results show that injection of a single low dose of emulsified PFCs into male rats can increase hepatic microsomal cytochromes P-450 concentration but the response is highly variable, depending on composition of emulsion injected. PMID- 2576744 TI - Effect of adafenoxate on different rat brain structures monoamine oxidase activity in vitro. AB - 1. The effect of the nootropic drug adafenoxate on monoamine oxidase (MAO) activity in rat brain cortex, striatum, hypothalamus and hippocampus has been studied using the following substrates: tyramine (total MAO), serotonin (MAO A) and beta-phenylethylamine (MAO B). 2. In a series of increased concentrations (from 5 x 10(-4) up to 1 x 10(-5) M) adafenoxate inhibits total MAO, MAO A and MAO B in the brain structures studied. 3. The adafenoxate IC50 values obtained illustrate its inhibitory properties and its lack of selectivity toward MAO in the brain structures isolated. 4. The results of our research prove the participation of MAO in the mechanisms through which adafenoxate affects the brain monoaminergic systems and realises its central effects. PMID- 2576745 TI - Alterations in rat mineral metabolism induced by acute ammonium acetate infusion. AB - 1. Acute ammonium intoxication in rat was produced by an i.v. overload of 1000 nmoles of ammonium acetate infunded during 15 min. 2. The load of ammonium produced sodium and potassium accumulation in muscle and plasma, minor in liver, and decreased these metal levels in kidney. 3. Blood and muscle magnesium content was strongly altered as a result of ammonium intoxication. 4. Calcium plasma levels, iron blood levels and iron hepatic stock diminished after the ammonium infusion. 5. Copper and zinc homeostasis were insignificantly altered. PMID- 2576746 TI - Evidence for the existence of the same endogenous digitalis-like factor in several mammalian species. AB - 1. Endogenous digitalis-like activity was studied comparatively in four mammalian species: guinea pig, dog, cow and rat. 2. Water extracts were prepared from guinea pig, dog, cow and rat hearts and assayed by ouabain radioreceptorassay, digoxin radioimmunoassay and digitoxin radioimmunoassay. Extracts were further analysed by fractionation by gel permeation chromatography with Sephadex G-25. 3. A similar behaviour was observed with the four species in the three assays. Extracts displaced tritiated ouabain binding to its receptor and labeled digoxin analogue binding to antidigoxin antibodies in a competitive manner. Displacement of labeled digitoxin analogue to antidigitoxin antibodies did not follow Michaelis-Menten kinetics. IC50 ratios between assays were similar for the four species studied. 4. Extracts from the four species exhibited a similar pattern when fractionated with Sephadex G-25. Endogenous digoxin-like immunoreactivity eluted after the salts, suggesting that the active material is of a molecular weight of less than 1000. 5. Results suggest that a similar endogenous factor endowed with digitalis-like characteristics is present in all mammalian species. PMID- 2576747 TI - Comparison of acetylcholine and alpha-bungarotoxin binding sites in insects and vertebrates. AB - 1. The nervous tissue of locusts contains high affinity as well as low affinity binding sites for acetylcholine which display a similar nicotinic pharmacology. 2. Hill plot analysis indicated a non-cooperative binding of acetylcholine. 3. In membrane preparations from locust ganglia and mouse brain the number of binding sites for ACh was about ten fold lower than for BGTX, whereas in membranes from electric tissue both sites occurred in similar concentrations. 4. Drug binding studies suggest that the high affinity binding sites for ACh and BGTX in preparations from insect and mouse are different; whereas in electric tissue both sites are very similar. 5. Precipitation experiments using immobilized BGTX and specific antibodies indicated that in insect nervous tissue as in electric tissue the ACh and BGTX binding sites are located on the same receptor molecule and occupy distinct partially overlapping binding sites, whereas in the vertebrate brain both sites are located on distinct binding proteins. PMID- 2576748 TI - Comparative incidence of experimental fascioliasis on corticosteroid pharmacokinetics in sheep. AB - 1. The kinetics of intravenously administered prednisone (0.5 mg/kg) and methylprednisolone hemisuccinate (4 mg/kg) were compared in two groups of four young male sheep before and regularly after experimental infestation with 150 metacercariae of Fasciola hepatica and 5 or 7 weeks following a flukicidal treatment administered post-infection at week 25. 2. Parasitic pathology was ascertained by clinical observation and by the increase in plasma antibodies directed against liver flukes. 3. The disposition of prednisone was altered with a significant decrease of plasma clearance occurring from eleven weeks after infection onwards. This change was parallel to an increase in the mean residence time of prednisone and of its major metabolite (prednisolone). 4. The same parasitic burden provoked only a slight decrease in the elimination half-life of methylprednisolone alcohol when its hemisuccinate ester was administered. PMID- 2576749 TI - Role of glutathione in the susceptibility of Trypanosoma cruzi to drugs. AB - 1. Glutathione (G-SH) concentration, gamma-glutamyltranspeptidase and glutathione S-transferase activities were studied in several strains of T. cruzi epimastigotes. GSH varied from 1.04 mM for the LQ strain to 0.61 mM for the Tulahuen strain. 2. Cultures of the LQ strain presented more resistance to drugs than those of the Tulahuen. It was necessary a concentration of nifurtimox 4 times higher and one of benznidazole 10 times higher in order to inhibit approximately to 50% the growth of LQ strain cultures when compared with the Tulahuen strain. 3. Buthionine sulfoximine decreased the concentration of glutathione to about 50% in the LQ and Tulahuen strains and potentiated the toxicity of nifurtimox and benznidazole in T. cruzi epimastigote cultures. These results suggest that glutathione is an important factor in the resistance of T. cruzi to nifurtimox and benznidazole. PMID- 2576750 TI - Uptake of copper from the bloodstream and its relation to induction of metallothionein synthesis in the rat. AB - 1. Female rats of the Wistar strain (12 weeks old; body wt, 200 g) were injected intravenously with a single dose of cupric chloride (0.8 mg Cu/kg body wt) and the uptake of copper (Cu) by the liver and kidneys was determined in relation to the disappearance of Cu from the bloodstream and the excretion to bile and urine. 2. Serum Cu level decreased rapidly within 30 min and then returned slowly to the control level by 3 hr post-injection, while the hepatic uptake of Cu continued linearly after the injection up to 4 hr post-injection. 3. The time lag between the disappearance of Cu from the blood serum and the uptake of Cu by the liver was not explained by the temporal distribution to red blood cells or by the enterohepatic circulation. 4. Cu taken up by the liver and distributed to its soluble fraction was bound to metallothionein, suggesting that the uptake of Cu by the liver depends on the induction of metallothionein synthesis. 5. Rapid uptake of Cu by the kidneys was observed at the beginning, which may indicate the role of the existing metallothionein in the control rat. PMID- 2576751 TI - Effect of GRF and somatostatin on 7B2 secretion by rat GH1 cells. AB - A novel pituitary protein "7B2" was secreted by GH1 cells. The secretion of 7B2 was increased in the presence of human GRF in a dose-responsive manner. In contrast, a somatostatin analog, SMS 201-995, revealed the inhibitory effects on the basal- and GRF-induced secretion of 7B2 at the concentration of 10(-7) M. These findings suggest that 7B2 is a secretory protein of rat GH1 cells under certain conditions. PMID- 2576752 TI - [AIDS. Dogmas and uncertainties]. PMID- 2576753 TI - A comparison of genomes of sheep pox virus isolates. AB - Sheep pox virus DNAs from field isolates and vaccine strains were analysed by digestion with the restriction enzymes PstI and Bam HI. The restriction profiles generated by these enzymes show very close relationship between isolates from different geographical regions. The patterns of isolates can be grouped by the animal of origin (e.g. a cattle pox isolate can be differentiated from sheep pox isolate). The molecular weights of the genomes of different isolates varied from 91 to 94 MDa. The restriction enzyme patterns can be used as a molecular epidemiological tool for differentiating field and vaccine isolates. PMID- 2576754 TI - Abnormal findings associated with undescended testis in Nigerian children. AB - Children between the ages of 6 years and 12 years numbering 2200, were examined for general physical development and external abnormality to correlate these anomalies with frequency of undescended testis. Whereas the overall frequency of undescended testis in this population was 0.5%, this condition was present in 1% of boys with peri-umbilical hernia. Undescended testis should be looked for in children with external congenital anomalies, particularly of the anterior abdominal wall. PMID- 2576755 TI - Kuwait drug addiction scene: a changing pattern? AB - Sociocultural considerations and persistence of indiscriminate prescription habits for addicts may have contributed in shifting the pattern of misused drugs from traditional alcohol and illicit drugs to predominantly iatrogenic dependence on benzodiazepines. The clinical profile and the rationale for the long-adopted detoxification treatment of 120 patients were studied. Multiple-drug misusers were found to suffer significantly more anxiety-type symptoms suggestive of benzodiazepine withdrawal. Poor correlation of detoxification medication with patient variables suggests that such treatment lacks the rationale for its continuation and should be replaced by treatments based on proper physical and psychiatric evaluation. Benzodiazepine dependence should be recognized as a clinical entity requiring relevant treatment strategies. PMID- 2576756 TI - Preclinical detection in Japanese families with myotonic dystrophy using polymorphic DNA markers. AB - Myotonic dystrophy (DM) is a genetic disease inherited by an autosomal dominant trait and characterized by multi-organ disorders. Although its biochemical basis has been unknown, the DM locus is closely linked to D19S19 and APOC2 on the long arm of chromosome 19 both in Japanese and Caucasian populations. Linkage studies of Japanese DM families using these polymorphic DNA markers detected two asymptomatic gene carriers in two unrelated families. PMID- 2576757 TI - Hypervariable polymorphism of autosomal origin detected by the Y-chromosome derived probe, pHY10. AB - A recombinant DNA probe (pHY10) hybridizing specifically to human DNA family DYZ1, 3,000 copies of which are present on the long arm of the Y chromosome, was used for probing human genome DNA digested with various restriction enzymes. To our surprise, the probe detected a hypervariable polymorphism of autosomal origin in human DNA when digested with TaqI. None of other 12 restriction enzymes revealed polymorphic patterns. Codominant segregation of the polymorphism was established in family studies. This probe has been widely used in the detection of the Y chromosome. Its ease of availability as well as highly discriminating polymorphic pattern makes it potentially very useful for forensic and human genetic purposes. PMID- 2576758 TI - Allele frequencies of MYCL and MYB protooncogenes in unrelated healthy Japanese. PMID- 2576759 TI - Morphological approach to the neurotransmission system. PMID- 2576760 TI - Growth hormone--physiological roles of endogenous GRF and somatostatin in its regulation. PMID- 2576761 TI - [P-glycoprotein and treatment with plicamycin + hydroxyurea in myeloid blastic crisis of chronic myeloid leukemia]. AB - The authors studied P-glycoprotein (P-gp) expression in three patients affected by myeloid blast crisis of chronic myeloid leukemia undergoing chemotherapy with plicamycin + hydroxyurea. P-gp is the molecular marker of multidrug resistance (MDR), and is able to promote the efflux of various drugs (including plicamycin) from the neoplastic cell. When resistance towards plicamycin and hydroxyurea association was observed, the blasts obtained from the three patients were found to express P-gp. Although P-gp may be not the unique mechanism responsible for resistance towards plicamycin and hydroxyurea association, the MDR phenotype may play an important role in the resistance towards this treatment protocol in the blast crisis of chronic myeloid leukemia. PMID- 2576762 TI - Histamine-mediated hyposmotic stimulation of gastric acid secretion. AB - Gastric glands incubated in hyposmotic medium (200 mOsm) accumulated aminopyrine, a measure of acid secretion, to the same extent as that of paired glands in isomotic medium containing histamine (10(-4) M). These maximal responses to hyposmolality and histamine were not additive. The hyposmotic response peaked earlier than the histamine response. Hyposmotic stimulation was nearly abolished by preincubation of the glands with metiamide and cimetidine, H-2 histamine antagonists. In the presence of histaminase, no hyposmotic stimulation occurred. The response to forskolin, a stimulant of adenylate cyclase, was equivalent in hyposmotic and isosmotic media. These results indicate that hyposmolality releases histamine from a paracrine cell in the gastric gland and that histamine binds to H-2 receptors on the parietal cell to initiate a cyclic AMP-mediated stimulation of acid secretion. PMID- 2576763 TI - Nitric oxide synthesis in endothelial cytosol: evidence for a calcium-dependent and a calcium-independent mechanism. AB - Release of nitric oxide (NO) from endothelial cells critically depends on a sustained increase in intracellular free calcium maintained by a transmembrane calcium influx into the cells. Therefore, we studied whether the free cytosolic calcium concentration directly affects the activity of the NO-forming enzyme(s) present in the cytosol from freshly harvested porcine aortic endothelial cells. NO was quantified by activation of a purified soluble guanylate cyclase co incubated with the cytosol. In the presence of 1 mM L-arginine, 0.1 mM NADPH and 0.1 mM EGTA, endothelial cytosol (0.2 mg of cytosolic protein per ml) stimulated the activity of guanylate cyclase 5.0 +/- 0.5-fold (from 31 +/- 9 to 153 +/- 15 nmol cyclic GMP formed per min per mg guanylate cyclase). Calcium chloride increased this stimulation further in a concentration-dependent fashion by up to 136 +/- 15% (with 2 microM free calcium; EC50 0.3 microM). The calcium-dependent and -independent activation of guanylate cyclase was enhanced by superoxide dismutase (0.3 microM) and was inhibited by the stereospecifically acting inhibitor of L-arginine-dependent NO formation NG-nitro-L-arginine (1 mM) and by LY 83583 (1 microM), a generator of superoxide anions. Our findings suggest a calcium-dependent and -independent synthesis of NO from L-arginine by native porcine aortic endothelial cells. PMID- 2576764 TI - [Acute abdomen in a patient with polyarteritis nodosa: report of a case]. AB - The authors present the case of a 31 year old woman admitted with abdominal pain, fever, weight loss and malignant hypertension. The ultrasonographic examination showed an image suggesting chronic nephropathy. On the 3rd day of hospitalization an exploratory laparotomy was performed with the diagnosis of acute abdomen. There was purulent peritonitis and a segment of ileum with multiple perforations, which was resected. The anatomopathologic finding of the surgical specimen revealed polyarteritis nodosa. The patient developed multiple organ failure and evolved to death. The difficulty in establishing the diagnosis is commented and, the authors according with some studies suggest treatment with plasmapheresis because the conventional therapy with methylprednisolone and cyclophosphamide proved to be insufficient in severe cases. PMID- 2576765 TI - A novel, fully automated rotometer for the study of turning behavior. Comparison of results under different experimental conditions. AB - The turning or circling activity of the rat is a very useful experimental model for the study of dopaminergic cerebral pathways. Quantification of turning makes it applicable to follow changes of pattern evolution in the same subject or for comparison between animals under different experimental conditions. Automated quantitative evaluation of turning has the advantage of its reliability, eliminates subjective inaccuracies and allows longer periods of observation. Therefore a fully automated rotometer aimed to accomplish these objectives was developed. It consists of a sensor box to transduce the circling movement of animals into computed information to be processed by a microprocessor and a printer for recording of results. The sensor was designed with a 16 holes perforated disc and two infrared receiver/emitter units. Pulses generated in the sensor box are computed and stored by the microprocessor. Reading of results may be made in manual or automated mode from the display or listed through the printer connected on-line. The reliability and validity of the rotometer were tested in animals submitted to different experimental conditions. Rats with unilateral chemical lesions (6-hydroxy-dopamine or kainic acid) of substantia nigra pars compacta rotated vigorously contraversive to lesion side after apomorphine injection (0.5 and 1 mg/kg, s.c.). Electrolytic lesion of the same nucleus made animals rotate ipsiversive to the lesion after apomorphine. To attain significant level of circling activity, the electrolytic lesion should be placed in the external boundaries of substantia nigra (265.8 +/- 53.4 turns/60 min for group with external placed lesion; (n = 5); 97.3 +/- 19.5 for group with internal placed lesion (n = 3); t = 2.31; p less than 0.05). Unilateral striatal lesion with ibotenic acid made animals rotate ipsilaterally with apomorphine as well as with the selective D-2 agonist bromocriptine (10 and 30 mg/kg, i.p.). Qualiquantitative differences in circling were observed between these two dopaminergic agonists. Comparison of circling activity on semispherical and flat surfaces showed a non significant trend to rotate more intensively on spherical surfaces but only in those animals turning greater than or equal to 3 turns/min. The results obtained with the automated rotometer herein described agree with those currently reported in the literature about the subject. They demonstrate also that this apparatus is adequate and reliable for the study of turning behavior under different experimental conditions. Interestingly enough, our observation on the specificity of electrolytic lesions placed in the lateral boundaries of substantia nigra to induce rotation is worth further investigation. PMID- 2576766 TI - Influence of 6-hydroxydopamine on ethanol narcosis in mice. AB - The effects of 6-hydroxydopamine (6-OHDA) i.c.v. on ethanol-induced narcosis were studied in mice, either untreated or pretreated with alpha-methyl-p-tyrosine (AMPT), p-chlorophenylalanine (PCPA) or 5-hydroxytryptophan (5-HTP). Mice treated with 6-OHDA 200 micrograms i.c.v., exhibited longer ethanol narcosis time than untreated controls. This effect was significantly increased when mice treated with 6-OHDA received AMPT (inhibitor of catecholamine biosynthesis) or 5-HTP (precursor or serotonin biosynthesis). After administration of PCPA (inhibitor of tryptophan hydroxylase) 6-OHDA did not prolong ethanol narcosis. Alcohol blood levels at awakening time were not significantly influenced by 6-OHDA. These results are consistent with the idea that a decrease in brain noradrenaline as well as an increase in brain serotonin enhance the narcotic action of ethanol, while both, the increase in brain noradrenaline and the decrease in brain serotonin shorten ethanol narcosis. PMID- 2576768 TI - HTLV-I associated myelopathy in Brazil: a preliminary report. AB - In this preliminary report the authors present the finding of a high prevalence (37.5%) of seropositivity of antibodies to HTLV-I tested by Western blotting in a sample of 16 Brazilian patients with chronic myelopathies of undetermined origin. PMID- 2576767 TI - [A clinical study of prevention of stress ulcer]. AB - The authors have studied the possibilities of preventing digestive bleedings caused by "stress ulcers" in a large number of risk-patients recovered in the Reanimation Center of St. Camillo in Rome. On 1012 patients recovered from 1985 to 1987 the authors have pointed out 69 cases of bleeding by "stress ulcer" (6.9%). The mortality was in these patients 75%. In every patient with risk factors the Authors have performed a prophylactic treatment. This treatment, achieved with randomized standards, has been performed in a group of 311 patients with ranitidine and in a second group of 170 patients with ranitidine and somatostatin joined. In the group of patients treated with ranitidine alone the incidence of digestive bleeding was of 30 patients (9.9%), in the second group treated with ranitidine and somatostatin the incidence was of 18 patients (10%). In a previous study the authors have noted an incidence of digestive bleeding by "stress ulcers" in the 16.6% of patients prophylactically treated with cimetidine and in the 8.66% in a first group of patients treated with anti-acids and in the 11.92% of a second group of patients equally treated with anti-acids. The authors point out that their results are disappointing in opposition to the good results relieved by other Authors possibly in connection with the seriousness, the number and the length of the risk factors in the patients they have treated. They believe that the results will be better when it will be possible to dispose of effective treatment able to increase the defensive powers of the gastric mucosa, seriously impaired by the stress factors. PMID- 2576769 TI - [Soldering for fixed prostheses. A critical analysis]. AB - In this study about in fixed prosthodontics, it's observed that casts must be built in one piece in bridges with rigid frame. Thus, occlusal contacts must fall upon closeness the abutments of bridges. PMID- 2576770 TI - Cellular activation and human immunodeficiency virus infection. PMID- 2576771 TI - The cellular immune response to the human immunodeficiency virus. PMID- 2576773 TI - [The effect of regulator peptides on pancreatic endocrine function in experimental acute pancreatitis]. AB - The comparative analysis of the influence on the glucose metabolism of rats in acute pancreatitis of synthetic analogues was made: somatostatin, calcitonin, leu enkefalin-dalargin. It was shown that dalargin has the maximum normalizing effect as a result of its antistress qualities. Physiological reaction of beta-cells is preserved in infusion of somatostatin. However, infusion of calcitonin results in the distortion of counterregulatory action of insulin and glucagon. PMID- 2576772 TI - Antiviral effects of CD4 derivatives. PMID- 2576774 TI - Immunohistochemical, morphometric, and ultrastructural investigations of the early development of insulin, somatostatin, glucagon, and PP cells in foetal human pancreas. AB - Fresh autopsy specimens of pancreas, taken from 18 human foetuses at the 10th (n = 4), 12th (n = 7), and 14th (n = 7) weeks of gestation, were analyzed immunohistochemically for the presence of islet parenchymal cells, immunoreactive with antisera raised against insulin (B cells), somatostatin (D cells), glucagon (A cells), and pancreatic polypeptide (PP cells). All four islet cell types were found sporadically within or near the epithelium of the small excretory ducts at the 10th week of development. At the 12th week, their presence appeared to be no longer restricted to the duct epithelium, as some B cells were found also in small clusters outside the ducts. At the 14th week of development, the B cells formed large clusters in the neighborhood of the excretory ducts. It is at this stage that the first parenchymal cells with Grimelius argyrophilia could be found. They were supposed to represent A cells. The B cells were found to be the predominating type of islet cells (about 50%) at the 10th week of gestation. The relative volume density was about 25% for the D cells, about 15% for the A cells, and about 10% for the PP cells. At the 12th and 14th weeks of development, the relative numbers of B and PP cells decreased somewhat (to 36 and 6%, respectively), whereas those of the D and A cells were found to increase (to 30 and 27%, respectively). The relative volume density of the total islet parenchyma was about 2, 6, and 21% at the 10th, 12th, and 14th weeks of development, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576775 TI - Carbon tetrachloride-induced liver cell injury in the Mongolian gerbil (Meriones unguiculatus). AB - 1. Male Mongolian gerbils (Meriones unguiculatus) liver activates CCl4 to free radicals that bind covalently to cellular components (CB) and stimulate a lipid peroxidation (LP) process to a larger extent than the rat liver. 2. CCl4 administration results in a less intense necrogenic effect in gerbils than in rats and does not cause fatty liver. 3. CCl4 causes less intense effects on liver ultrastructure or calcium metabolism but more marked depression of glucose 6 phosphatase activity (G6P-ase) in gerbils than in rats. 4. Results suggest that a better ability of gerbil liver to keep calcium homeostasis than rat liver might be the cause of their relative resistance to necrosis. Higher intensity of CB and LP in gerbils than in rats might explain more intense effects on G6P-ase. PMID- 2576776 TI - Deltamethrin causes changes in protein phosphorylation activities associated with post-depolarization events in the synaptosomes from the optic lobe of squid, Loligo pealei. AB - 1. Deltamethrin causes a significant change in protein phosphorylation activities which follow depolarization. 2. The most significant change caused by deltamethrin was the prolonged elevation of the level of phosphorylation on a number of key synaptic proteins beyond the normal time of their recovery to the dephosphorylated state. 3. The best marker proteins reacting to deltamethrin in this manner were calcium-calmodulin dependent protein kinase and synapsin I. PMID- 2576777 TI - Catalase is needed to avoid tissue peroxidation in Rana perezi in normoxia. AB - 1. In order to clarify the relative role of catalase (CAT) and glutathione peroxidases (GSH-Px) at normal and high O2 tensions, Rana perezi frogs were chronically treated with aminotriazole (AT), hyperoxia, or both. 2. A 100% survival was observed with both treatments. Hyperoxia increased liver catalase and kidney TBA-RS and decreased GSH-Px. 3. AT caused quantitatively higher alterations than hyperoxia in both organs: CAT was depleted, TBA-RS increased (114% in kidney) and GSH-Px decreased. 4. It is concluded that in Rana perezi (a) CAT, in spite of its much higher KM and Vmax in relation to GSH-Px, is needed to avoid oxidative stress even in normoxia; (b) normoxic tissues have significative amounts of H2O2; (c) GSH-Px does not compensate the lack of CAT. PMID- 2576778 TI - Seizures in the Mongolian gerbil are related to a deficiency in cerebral glutamine synthetase. AB - 1. Seizure prone (SP)-gerbils (Meriones unguiculatus) tested repeatedly in an open field exhibited habituation of seizures after one or two trials and subsequently showed more ambulatory activity than non-seizure prone (NSP) individuals. 2. A subset of 5 SP and 5 NSP animals were killed and portions of each cerebral hemisphere, the cerebellum and the brainstem medulla were analysed for glutamine synthetase (GS). 3. GFAP immunohistochemistry was used on forebrain sections to assay astrocyte density. 4. It was found by MANOVA, PCA and regression analyses that seizures and ambulatory activity were related to a deficiency in cerebral GS. 5. Rearing behaviour was related to medullary brainstem and cerebellar GS concentrations. 6. The decreased GS of the seizure prone gerbils was not apparently associated with a deficiency of astrocytes, perhaps the reverse. 7. The results are discussed in relation to glial-neuronal interactions modulating arousal and the propensity for seizures. PMID- 2576779 TI - Endothelium attenuates contractile responses of goat saphenous arteries to adrenergic nerve stimulation. AB - 1. Field electrical stimulation of perfused segments (15 mm long) of the goat saphenous artery caused frequency-dependent increases in perfusion pressure which were blocked by tetrodotoxin, phentolamine or prazosin. 2. Mechanical removal of the endothelium augmented both resting perfusion pressure and responses to electrical stimulation. 3. Methylene blue enhanced responses with intact endothelium only. It is likely that the endothelium exerts part of its inhibitory influence through the activation of guanylate cyclase. PMID- 2576780 TI - In vitro metabolism of the pro-carcinogen aflatoxin B1 by liver preparations of the calf, nurse shark and clearnose skate. AB - 1. Liver postmitochondrial supernatant preparations of calf, clearnose skate, and nurse shark were able to metabolize the fungal toxin aflatoxin B1 to various metabolites. 2. Calf liver produced aflatoxin M1 and Q1 as the major chloroform soluble metabolites, with small amounts of aflatoxicol formed during incubation. 3. Liver preparations of the elasmobranchs, however, produced aflatoxicol as the major chloroform soluble metabolite with no other metabolite being detected. 4. The water soluble metabolite profiles for the three species were also quite different with the tris diol adduct being produced to a much greater extent in calf liver preparations. 5. Aflatoxicol production by the elasmobranch liver homogenates was reversible with the skate reconverting a large amount (30%) of aflatoxicol to AFB1. The nurse shark, however, appeared to convert a portion of aflatoxicol to an unknown metabolite more polar than AFB1. 6. Calf liver DNA bound approximately 3 x more 3H-AFB1 than shark liver DNA. PMID- 2576781 TI - Biogenic amines and active peptides in extracts of the skin of thirty-two European amphibian species. AB - 1. Extracts prepared from fresh or dried skins of 32 European amphibian species were submitted to chemical (colour reactions) and biological screening to determine the occurrence and contents of biogenic amines and peptides active on smooth muscle preparations and blood pressure. 2. Only indolealkylamines were detectable in the skins. They were represented by tryptamine, 5 hydroxytryptamine, and its N-methylated, cyclized and sulphoconjugated derivatives. 3. The peptide families identified in the extracts were as follows: bombesins (bombesin and alytesin), bradykinins (bradykinin, bradykinin 1-8, bradykinin 1-7), chemotactic peptides (RECP I, II and III), bombinins and TRH. Bombesins, bombinins and TRH (thyrotropin-releasing hormone) were isolated from skin extracts of discoglossid frogs; chemotactic peptides and again TRH from extracts of ranid frogs. 4. Further research will certainly lengthen the list of active peptides in the skin of European amphibians, as is the case with Australian, American and African amphibians. PMID- 2576783 TI - The identification, localization, and pharmacology of FMRFamide-related peptides and SCPB in the penis and crop of the terrestrial slug, Limax maximus. AB - 1. The molluscan neuropeptides FMRFamide, pQDPFLRFamide, and SCPB were tested on the isolated crop and penis of the terrestraial slug, Limax maximus. FMRFamide and pQDPFLRFamide stimulated the penis and inhibited contractions of the crop. In contrast, SCPB either stimulated or relaxed the penis and increased the tone of the crop. 2. Fibers and varicosities containing immunoreactive (ir-) FMRFamide and ir-SCPB were located in the penis and crop. 3. Extracts of penes, crops, ganglia, and whole animals all contained FMRFamide, FLRFamide, SDPFLRFamide, NDPFLRFamide, and pQDPFLRFamide. 4. These results suggest that the FMRFamide related peptides and SCPB are involved in the regulation of the reproductive and digestive activities of Limax. PMID- 2576782 TI - Xenobiotic biotransformation in the Pacific oyster (Crassostrea gigas). AB - 1. Oyster visceral mass and gill tissues possessed measurable flavin-containing monooxygenase (FMO) activity. 2. FMO activity was confirmed in visceral mass microsomes by oxygen uptake experiments utilizing various nitrogen and sulfur containing chemicals along with measurement of N,N-dimethylaniline (DMA) N oxidase and methimazole oxidation activities. DMA N-oxidase and methimazole oxidation activities also were present in gill microsomes. 3. Excluding oyster gill methimazole oxidation, there were no consistent seasonal differences in FMO activity in oyster gill or visceral mass microsomes. 4. Although lacking spectral evidence for cytochrome P-450, a peak at 418 nm was observed along with NADPH cytochrome c reductase activity in visceral mass and gill microsomes suggesting the presence of a denatured cytochrome P-450 system. 5. NADPH-independent benzo(a)pyrene hydroxylase (BPH) activity was observed in both oyster visceral mass and gill microsomes suggesting a co-oxidation pathway possibly involving a one electron transfer of oxygen from a lipid hydroperoxide. PMID- 2576784 TI - Continuous administration of 5-hydroxytryptamine alters cellular immunity in chickens. AB - 1. 5-Hydroxytryptamine administered continuously through osmotic pumps altered the PHA wattle response and in vitro leukocyte capillary tube migration in UNH 105 chickens. 2. Administration of 100 ng/hr 5-hydroxytryptamine for 48 hr significantly suppressed the PHA wattle response. 3. In vitro leukocyte migration was significantly enhanced by 72 hr exposure to 5-hydroxytryptamine at a dose of 100 ng/hr. PMID- 2576785 TI - Effects of paraoxon on spike initiation and conduction block in the giant interneurons of the American cockroach, Periplaneta americana. AB - 1. The effects of paraoxon were studied on spike initiation and conduction in the giant interneurons (GIs) of the American cockroach, using electrophysiological techniques. 2. Paraoxon treatment induced high-frequency bursts in GI axons. During these bursts, overshooting spikes recorded in the sixth abdominal ganglion were replaced, in phase, by small, decremental potentials. 3. These small potentials were not EPSPs since current injection could modulate their frequency. 4. An analysis of anteriorly conducted spikes indicates that the site of spike initiation is located near the dendritic region of the GI and is unchanged by paraoxon treatment. PMID- 2576786 TI - Image analysis of the sympathetic innervation of the myenteric plexus in the small intestine of mammalian species. AB - 1. The arrangement of the sympathetic innervation of the myenteric plexus varies between mammalian species. 2. In larger mammals the density of sympathetic innervation of the myenteric plexus is significantly less than in small (less then 1 kg) species. 3. The number of varicosities on the terminal parts of sympathetic neurons innervating the gut is significantly less in larger mammals. PMID- 2576787 TI - Effects of phenobarbital and 3-methylcholanthrene on the hepatic cytochrome P-450 metabolism of various alkoxyresorufin ethers in the cotton rat (Sigmodon hispidus). AB - 1. Microsomes isolated from phenobarbital and 3-methylcholanthrene induced cotton rats (Sigmodon hispidus) were tested for o-dealkylase activity with methoxy-, ethoxy-, pentoxy- and benzoxyresorufin ethers. 2. The activity of 3 methylcholanthrene induced microsomes was greater than controls. 3. Activity of phenobarbital induced microsomes was not different from controls. 4. There was a distinct difference between male and female animals. 5. The results obtained from cotton rats are markedly different from results obtained from Sprague-Dawley (S D) rats. PMID- 2576788 TI - Acetylcholine sensitivity of the spine-test articular capsule of the sea urchin Eucidaris tribuloides. AB - 1. The changes in the consistence of the spine-test articular capsule, or ligament, of the primary spines of Eucidaris tribuloides induced by acetylcholine (ACh) have been studied. Two complementary techniques were used: (a) "forced vibration", which detects variations in the stiffness of the ligament along a single diametral plane; and (b) "forced-rotation" which records the spatial distribution of those changes. 2. ACh (1 microM to 1 mM) caused a rapid increase in the resistive force opposed by the ligament to passive stretching. Similar effects were elicited by several monoquaternary, N-substituted derivatives of trimethylammonium. 3. The opposite effect, i.e. softening, was induced by decamethonium, dimethylphenylpiperazine, and 2-ketoamyltrimethylammonium. 4. The involvement in these effects of ACh-binding groups with pharmacological properties similar to those of the "anionic sites" of nicotinic ACh receptors is suggested. PMID- 2576789 TI - Diurnal alterations of catecholamines, indoleamines and their metabolites in specific brain regions of the mouse. AB - 1. The diurnal variations of regional brain concentrations of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and metabolites were determined in unperturbed male CD-1 mice. Determinations were made every 4 hr for 24 hr. 2. The most striking and significant variations in biogenic amines were seen in the hypothalamus, where concentrations of NE, DA and 5-HT varied in a rhythmic pattern and as much as two-fold during this period. 3. In some cases, daily alterations in parent biogenic amines were reflected by concurrent changes in their metabolites. 4. Since concentrations of neurotransmitters in the brain are often used as an indicator of stress and/or toxicity, these data should provide an accurate data base allowing for more accurate interpretation of results. PMID- 2576790 TI - Rat kidney function related to tissue glutathione levels. Effects of different glutathione depletors. AB - 1. Rat renal function was evaluated during acute depletion of glutathione (GSH) produced by different doses of diethyl-maleate (DEM) or buthionine-sulfoximine (BSO). 2. Similar alterations in renal function were observed when similar GSH levels were obtained independently of the GSH depletor employed. 3. These results confirm the relationship between GSH levels and renal function. PMID- 2576791 TI - Impaired surfactant function in 3-methylindole-induced lung injury in goats. AB - 1. This study was designed to monitor the changes in surfactant quantity and function in the 72 hr following 3-methylindole (3MI) infusion in goats. 2. 3MI, at 35 mg/kg body wt, caused an increase in surfactant phospholipid isolated from lamellar bodies and lavage fluid. 3. The function of surfactant isolated from lavage fluid was tested using the pulsating bubble surfactometer. The results indicated a serious impairment in the ability to lower surface tension in vitro. 4. Results suggested 3MI caused an impaired surfactant function rather than surfactant synthesis in response to epithelial damage. PMID- 2576792 TI - Cytochrome P-450-dependent metabolism of xenobiotics. A comparative study of rat hepatic and plant microsomal metabolism. AB - 1. A comparison was made between rat hepatic and plant microsomal cytochrome P 450 and cytochrome P-450 linked enzymic activities. 2. The results show that, compared with plant microsomes, rat hepatic microsomal protein concentrations were 165-fold higher, and rat hepatic cytochrome P-450 concentration were 32-fold higher. 3. Rat hepatic Cytochrome P-450 linked enzyme activities were 1765-fold and 25-fold greater when compared with plant microsomes using aldrin and biphenyl as substrates, respectively. 4. Rats metabolised biphenyl to 2- and 4 hydroxybiphenyl, whereas plants produced only the latter metabolite. 5. Pretreatment of rats and plant tissues with biphenyl, Aroclor 1248 and the sodium salt of phenobarbital increased significantly the microsomal protein concentrations, and enzyme activities linked to cytochrome P-450. 6. Unlike rat microsomes, those of plants were unable to metabolise halosubstituted biphenyls at measurable rates. PMID- 2576793 TI - In vitro effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on muscarinic cholinergic receptors in mouse striatum. AB - 1. MPTP significantly lowered Kd of the binding of [3H]QNB to muscarine receptor without affecting Bmax values compared with those of control. Hill coefficients (nH) of control and MPTP (250 microM) added group were 1.15 +/- 0.127 and 0.56 +/ 0.202, respectively. 2. Prior addition of pargyline to MPTP did not prevent the decrease of [3H]QNB binding. The patterns of displacement of [3H]QNB by MPTP and MPP+ were similar to those by some muscarinic agonists, such as acetylcholine, carbamyl choline and methacholine. 3. These results suggest that MPTP might be muscarinic agonist and might play a role to produce Parkinsonism through directly affecting the muscarinic cholinergic receptors in vivo. PMID- 2576794 TI - Effect of cholecystokinin octapeptide and somatostatin on the motility of guinea pig and canine gallbladder. AB - Species differences have been observed in the effect of cholecystokinin octapeptide (CCK OP) on the canine and guinea pig gallbladder smooth muscle motility. 1. CCK OP was more potent stimulant in canine than in guinea pig gallbladder smooth muscles. Its pD2 values were 10 and 9.2, respectively. 2. The acetylcholine (10(-4) M)-induced maximum contractions in canine gallbladder muscle strips were by 50% lower as compared to the CCK OP (10(-8) M) maximum responses while in guinea pig gallbladder muscle strips the acetylcholine (ACh) maximum responses were by 20% lower than the CCK OP maximum responses. 3. CCK OP increased [3H]ACh release by 27% in canine gallbladder and by 40% in guinea pig gallbladder. 4. Somatostatin (SOM) had not any direct myogenic effect in guinea pig and canine gallbladder but it decreased [3H]ACh release from gallbladder intrinsic cholinergic neurons. PMID- 2576795 TI - Inducibility of liver cytosolic aldehyde dehydrogenase activity in various animal species. AB - 1. The inducibility of hepatic cytosolic aldehyde dehydrogenase activity was studied in rat, mouse, guinea pig, chicken, frog, salamander and rainbow trout, by using two different types of inducers of drug metabolism. 2. Phenobarbital (a type I inducer of drug metabolizing enzymes) increased total liver cytosolic aldehyde dehydrogenase activity (up to 20-fold) in a genetically defined substrain of responsive rats (RR) and only slightly, if at all, in a non responsive substrain (rr). On the contrary, both types of rats showed a highly induced aldehyde dehydrogenase activity after treatment with methylcholanthrene (a type II inducer). Phenobarbital is affecting mainly an isozyme of aldehyde dehydrogenase which is best measured with propionaldehyde as the substrate and NAD as the coenzyme (P/NAD). 3. Administration of phenobarbital to mice produced only a slight increase (2-fold) in the P/NAD aldehyde dehydrogenase activity. 4. Methylcholanthrene treatment caused a 2-fold increase of the hepatic P/NAD aldehyde dehydrogenase activity in the chicken. 5. In the guinea pig, phenobarbital produced an approximate 3-fold increase of the P/NAD activity. Methylcholanthrene had a similar effect, although to a lesser extent. 6. In the salamander, a 4-fold increase was detected in the enzyme activity measured with benzaldehyde as the substrate and NADP as the coenzyme (B/NADP), after treatment with either phenobarbital or methylcholanthrene. 7. The hepatic aldehyde dehydrogenase activities were found unchanged in the rainbow trout, after treatment with phenobarbital or 2,3,7,8-tetrachlorodibenzo-p-dioxin. 8. The rat model remains the only one examined that shares with human hepatocytes strong inducibility of the B/NADP aldehyde dehydrogenase isozyme upon treatment with polycyclic aromatic hydrocarbons. PMID- 2576796 TI - Drug metabolism components in liver microsomes from Hypostomus punctatus, a Brazilian benthic fish (Cascudo). AB - 1. The major components of hepatic drug biotransformation system were identified in a Brazilian freshwater benthic fish. 2. Cytochrome P-450 difference spectra were obtained adding 0.02 mM phenazine ethosulphate and 2 mM ascorbate to microsomal suspensions. Basal levels of P-450 were high (0.9 nmol/mg of microsomal protein) and were not induced by 3-MC. 3. Microsomal NADPH-cytochrome C reductase activity was determined in presence of 1.3 x 10(-4) M NADPH, 3.3 x 10(-5) M cytochrome C, 1.0 x 10(-4) M EDTA, 66 micrograms of microsomal protein per ml in a 0.3 M Tris-HCl buffer, pH 8.6. Basal levels of NADPH-cytochrome C were 152.7 nmoles/min/mg of microsomal protein. PMID- 2576797 TI - Measurement of the relative binding affinity of zearalenone, alpha-zearalenol and beta-zearalenol for uterine and oviduct estrogen receptors in swine, rats and chickens: an indicator of estrogenic potencies. AB - 1. The relative binding affinity of zearalenone, alpha-zearalenol, and beta zearalenol for estrogen receptors was determined in the pig, rat and chicken. 2. Similar relative binding patterns were observed, with alpha-zearalenol exhibiting greater affinity than zearalenone and beta-zearalenol the least binding affinity in all species. 3. The relative binding affinity of alpha-zearalenol was greater in pig, than in rat and significantly greater than in chicken. 4. Interspecies differences in zearalenone sensitivity may be due to the binding affinity of alpha-zearalenol for estrogen receptors and differences in zearalenone metabolites formed. PMID- 2576798 TI - The ribonucleoprotein structures along the pathway of mRNA formation. AB - Heterogeneous nuclear RNAs (hnRNAs), some of which are mRNA precursors, and the mature mRNAs are associated in eukaryotic cells with specific proteins to form ribonucleoprotein complexes (RNP). The RNP proteins are likely to play a major role in the formation, packaging, processing, and function of mRNA. The major proteins that interact with hnRNA and with mRNA were identified by photochemical RNA-protein cross-linking in intact cells and monoclonal antibodies to several of these proteins were produced. Using these antibodies the hnRNP proteins were characterized and the hnRNP complex was isolated from vertebrate cell nuclei. The hnRNP complex is a unitary structure of consistent, defined and conserved components. The proteins of the hnRNP complex were identified and the general organization of hnRNA and proteins in the hRNP complex were studied. PMID- 2576799 TI - [Usefulness of transesophageal electrophysiological study during the ergometric test in the evaluation of supraventricular paroxysmal tachycardia occurring during exertion]. AB - Transesophageal electrophysiologic study has recently been proposed for the evaluation of supraventricular arrhythmias. In this report we present 13 cases, with palpitations occurring only during effort, due to a suspected supraventricular tachycardia, in which the usefulness of the transesophageal electrophysiologic study performed during stress test was evaluated. Of these 13 patients, nine were male and four were female, mean age was 29 yrs. Twelve cases had no heart disease, one had a moderate mitral valve insufficiency. Nine cases had a normal ECG, four had a WPW pattern. In 9/13 cases no significant arrhythmia was ever documented, in 1/13 ventricular premature beats were present in the basal ECG, in 1/13 a atrial fibrillation and in 2/13 a supraventricular reciprocating tachycardia was recorded. In all cases a maximal exercise test and a 24-hour Holter monitoring were performed. In all pts a transesophageal electrophysiologic study was performed both at rest and during extra-stimuli and incremental atrial pacing. The end point of transesophageal study was the induction of a sustained (greater than 30") supraventricular tachycardia. RESULTS. Maximal exercise test was negative in 11/13 cases; it showed ventricular premature beats in one case and initiated a supraventricular tachycardia in one. The 24 hour Holter monitoring was negative in 12/13 cases while it showed frequent ventricular premature beats in one. Resting transesophageal electrophysiologic study revealed dual A-V nodal pathways in six pts: in one of them a junctional re-entry was induced; in two a single echo beat was observed, while in three no reentry was observed. In three cases a supraventricular tachycardia was induced which was sustained in one and unsustained (7" and 24") in two cases. In 4 cases transesophageal electrophysiologic study gave no information. Transesophageal stimulation during exercise induced a greater than 30" reciprocating tachycardia in all patients, at work loads of 30-180 watts. Six pts had an intranodal tachycardia (V-A less than 70 msec) a further six pts had a atrioventricular tachycardia involving a Kent bundle (V-A greater than or equal to 70 msec), which was concealed in two, and one had a atrial tachycardia. In four cases (3 with intranodal and 1 with atrioventricular tachycardia), exercise transesophageal study was repeated after chronic therapy with betablockers (sotalol 240 mg/die or metoprolol 200 mg/die). In all cases, after therapy, the induced tachycardia had a longer cycle and in two cases it was induced at a higher work load. In a further two cases flecainide (200 mg/die) was tested. In one case (with atrial tachycardia), the arrhythmia was no longer inducible after therapy, in another case (with intranodal tachycardia) the drug had no effect. CONCLUSIONS. In patients with paroxysmal supraventricular tachyarrhythmias occurring during effort the basal ECG is normal or shows a WPW pattern. The maximal exercise test and 24 hour Holter monitoring give no information in over 90% of cases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2576800 TI - Changes in the morphological status of some internal organs in animals exposed to the action of chemicals. PMID- 2576801 TI - Treatment and prevention of nonsteroidal anti-inflammatory drug induced gastrointestinal mucosal injury. AB - It is generally recognized that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can cause varying degrees of gastroduodenal mucosal damage. These agents are most frequently used by physicians for rheumatic diseases because of their high effectiveness in reducing joint pain and swelling. Four classes of drugs, namely histamine (H2) blockers, antacids, sucralfate and prostaglandins are available for treatment of gastric mucosal damage caused by NSAIDs. All these drugs are very effective in healing gastric and duodenal injury if nonsteroidal anti-inflammatory drugs are discontinued. However, current data suggest that if nonsteroidal anti-inflammatory drugs are continued while gastrointestinal damage is present there may be significant differences among these drugs in healing of gastric mucosal damage. Synthetic prostaglandins are therapeutically superior over other forms of treatment when nonsteroidal anti-inflammatory drugs are continued in the presence of gastric mucosal injury. This article is a review of such data from the literature for a) the treatment and b) the prevention of gastrointestinal damage due to aspirin and nonsteroidal anti-inflammatory drugs. PMID- 2576803 TI - Different respiratory patterns elicited by microinjection of L-glutamic acid into the ventrolateral nucleus of the tractus solitarius in cats. AB - Only limited information relating neurotransmitters to central regulation of the respiratory system exists. L-glutamic acid has been proposed as the primary neurotransmitter in the nucleus of the tractus solitarius (NTS) of cats. To test whether or not glutamic acid has an effect on the respiratory center, we microinjected L-glutamic acid (1 M, 0.1 microliter) via a 1 microliter Hamilton microsyringe into the ventrolateral area of the NTS dorsal respiratory groups (DRG) of unanesthetized, decerebrated cats at two-second intervals with continuous monitoring of tidal volume (VT), respiratory rate (f), end tidal CO2, blood pressure and heart rate. The results showed that glutamate induced the following respiratory changes: VT and f increased; VT and f decreased; and VT decreased but f increased. In addition to VT or f changes elicited by glutamate microinjection, changes in other rhythmic patterns such as apnea, apneusis and irregular respiration were observed. Glutamic acid appears to play a significant role in the modulation of the respiratory drive in the DRG. We, therefore, suggest that the excitatory amino acid L-glutamic acid may be involved in central respiratory control. PMID- 2576802 TI - Polyarteritis nodosa. An unusual cause of acute abdomen. AB - Two cases of acute abdomen operated on twice and biopsy specimens confirmed are presented. The diagnosis of a systemic necrotizing vasculitis group of polyarteritis nodosa was established. The syndrome affects predominantly males between the second and forth decade of life. The gastrointestinal tract is involved in approximately 50% of the cases. While a negative laparotomy may be considered as a surgical pit-fall, nevertheless, it is the only way of establishing the diagnosis and treating the complications of the disease in some of the cases. PMID- 2576805 TI - The T-cell receptor alpha, beta and gamma polymorphism in Japanese. AB - Polymorphism in the genes encoding the alpha (alpha), beta (beta) and gamma (gamma) chains of the human T-cell receptors was analyzed both in population and family studies. Against twelve unrelated Japanese, several out of the 15 restriction endonucleases tested, revealed restriction fragment length polymorphism. The segregation of the polymorphic fragments were confirmed among 15 members of three families. In most of the cases paternal and/or maternal haplotypes could be assigned. By testing the polymorphic enzymes among the random healthy Japanese, the frequency of each polymorphic fragment was then determined. Although the polymorphism found in this study was similar to that reported in Caucasians, some differences were observed. Such differences are discussed. The restriction fragment length polymorphism in both population and family studies, derived from alpha, beta and gamma chains of the T-cell receptor found in this report, might be useful markers for genetic analysis of the T-cell function in relation to immunological disorders. PMID- 2576804 TI - Metabolism of gamma-linolenic acid in primary cultures of rat hepatocytes and in Hep G2 cells. AB - Incorporation and metabolism of gamma-linolenic acid (GLA) in both rat hepatocytes and Hep G2 cells were compared to those of oleic (OA), linoleic (LA), alpha-linolenic (LLA), and dihomo-gamma-linolenic (DGLA) acids. The incorporation of GLA into both types of cells was higher than LLA and DGLA, but lower than OA and LA. It was efficiently converted into DGLA in both types of cells and increased the concentration of DGLA. LLA was converted to a small amount of C20:4 (n-3) only in Hep G2 cells. Incubation with LA, GLA, LLA, and DGLA did not increase the concentration of arachidonic acid (AA) in both types of cells. LA. GLA, LLA, and their metabolites were incorporated into phosphatidylcholine, but only GLA and its metabolite, DGLA, were also incorporated into phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. The coexistence of GLA and LLA during their catabolism diminished the amounts of respective metabolite in Hep G2 cells. The presence of GLA inhibited completely the formation of C20:4(n-3) from LLA. The results indicate that GLA is more effective in raising the ratio of DGLA/AA. Also, polyunsaturated fatty acids of n 3 and n-6 series have competitively catabolized in both types of hepatocytes. PMID- 2576806 TI - Restriction fragment length polymorphisms of X chromosome among Japanese population. AB - Restriction fragment length polymorphisms were studied among the Japanese using 13 polymorphic DNA probes on the X chromosome. For 6 probes (pPA4B, cpX203, p58 1, pHPGK-7e, cpX289 and 7b) the allelic frequencies were the same as those for Caucasians, but they were quite different (p less than 0.01) for 4 probes (dic56, pOTC (MspI), pTAK8B and pXG-16 (HindIII)). No polymorphisms were observed for 4 probes (pG95 alpha 1-7dIII/RI (n (chromosome number studied) = 54), pXG-16 (TaqI) (n = 50, p8 (n = 108), and pXG-17 (n = 76). These results suggest that not a small number of DNA probes currently available are useless for linkage analysis in Japan. PMID- 2576807 TI - [The treatment of male infertility with the preparation vitaton]. AB - Thirty men with fertility disorders, 21 to 42 years of age (mean 29 years) and mean duration of sterile matrimony 4 years 7 months received Vitaton treatment. The patients were divided in three groups: 8 with cryptorchidism, 12 having undergone resection of v. testicularis interna sin for varicocele and 10 with idiopathic oligospermia. In the first group of patients with bilateral cryptorchidism and azoospermia the control spermatograms showed persistence of azoospermia, i.e. in none of these patients was fertility reestablished. The second group of patients who had been operated for idiopathic varicocele experiences significant improvement in spermatozoid motility. In the third group (with idiopathic oligospermia) spermatozoid viability was improved--more than 50 per cent motility and more than 10 mu/sec speed of the spermatozoa. Application of Vitaton in andrologic practice gives justifiable hopes for improvement of spermatozoid motility and speed, which are the most important parameters for male inseminating capacity. PMID- 2576808 TI - [2 cases of gastrinomas, one of which is combined with multiple endocrine neoplasms]. PMID- 2576809 TI - Expression of the Thy-1 gene and Thy-1-derived fusion genes in transgenic mice. PMID- 2576810 TI - Some central effects of repeated treatment with fluvoxamine. AB - We investigated the effect of repeated treatment with fluvoxamine, a selective serotonin uptake inhibitor, on behavioral effects of dopaminomimetics and methoxamine and on the animal behavior in the "behavioral despair" test. A repeated treatment with fluvoxamine (twice daily for 14 days) potentiated in mice and in rats (weaker) the amphetamine-induced hyperactivity. The hyperactivity induced by nomifensine in mice remained unaffected by fluvoxamine. The stimulation of locomotor activity by intracerebroventricularly administered methoxamine was not affected by repeated treatment with fluvoxamine. Given three times fluvoxamine had no effect on the immobilization time in the "behavioral despair" test in rats. The results indicate that fluvoxamine given repeatedly acts differently than citalopram, another selective serotonin uptake inhibitor, and differs also from other antidepressant drugs. PMID- 2576811 TI - Pharmacological studies on the central action of novel benzylidene imidazothiazolone derivatives. AB - Pharmacological studies on the central action of novel benzylidene imidazothiazolone derivatives were carried out on mice and rats. The highest activity showed two compounds: a chloro- and a methoxy- derivative. They produced analgesic, anticonvulsant, anti-anxiety and "antidepressant" effects in mice. PMID- 2576812 TI - [Denopamine responsive pulmonary hypertension in a patient with collagen disease]. AB - We report a 52-years-old female patient with collagen disease and pulmonary hypertension. Denopamine, beta-adrenergic agonist, decreased her high pulmonary arterial pressure and improved dyspnea on exercise after long term use. She had suffered from Raynaud's phenomenon, pulmonary fibrosis, shortening of lingual frenulum and positive ANA and RA test. Although her pulmonary fibrosis had been well controlled by azathioprine, dyspnea on exercise became worse, so she admitted to our hospital for further examination in Feb 1988. Right heart catheterization revealed her high pulmonary arterial pressure (mean 29 mmHg). Under right heart catheterization, denopamine markedly decreased her pulmonary arterial pressure and increased her cardiac output. After about 6 weeks' use of denopamine, her mean pulmonary arterial pressure decreased to 15 mmHg, PO2 increased from 43 to 62 mmHg and dyspnea improved. Denopamine has been regarded as a selective beta 1-adrenergic agonist. In this case, denopamine might have beta 2-agonist effect to dilate pulmonary vasculature, or have secondary effect to increase PO2 by the improvement of cardiac function. Denopamine might be useful for pulmonary hypertension with collagen diseases. PMID- 2576813 TI - Chromosomal aberrations as a contributing factor for tumor promotion in the mouse skin. AB - Tumor promotion in mouse skin can be dissected in two stages: stage I (conversion) and stage II. Whereas for stage II clonal expansion of transformed cells is believed to play a major role, the mechanism(s) underlying conversion is still a matter of debate. Because conversion can be achieved upon treatment with phorbol ester tumor promoters prior to initiation, it is unlikely to represent simply proliferative stimulation of initiated cells (due to epigenetic changes induced). Since tumor promoters exert clastogenic activities and, on the other hand, the clastogen methyl methanesulfonate proved to be convertogenic, the possibility arises that chromosomal changes are involved in conversion. Based on this hypothesis, several findings concerning the action of tumor promoters and the process of tumor promotion in the mouse skin system are discussed and interpreted: the frequency, reversibility, and transient nature of conversion, dependence of tumor promotion on DNA synthesis, induction of DNA breaks by tumor promoters, and the protecting effect of scavengers of free radicals. A model is presented suggesting tumor formation in mouse skin (and other systems) to proceed in discrete, genetically determined steps. Initiation is considered to be due to the induction of point mutations in a dominant-acting oncogene that becomes thereupon activated, whereas the decisive event in the conversion stage of tumor promotion is the induction of numerical and/or structural chromosomal changes with the consequence of loss or inactivation of gene(s) involved in suppression of the tumor phenotype. PMID- 2576814 TI - Tetrachloroethane, pentachloroethane, and hexachloroethane: genetic and biochemical studies. AB - Tetrachloroethane (TTCE), pentachloroethane (PCE), and hexachloroethane (HCE) were tested in diploid strain (D7) of the yeast Saccharomyces cerevisiae in suspension test with and without mammalian metabolic activation (S9). TTCE, PCE, and HCE gave positive results on cells harvested from logarithmic growth phase; only PCE induced a significant increase (P less than or equal to .01) of mitotic gene conversion and point reverse mutation on cells from stationary growth phase with metabolic activation (S9). The in vivo effects on cytochrome P450 content (cyt. P450), pentoxyresorufin O-dealkylase (P450-like, class IIB, PROD), and ethoxy-resorufin O-deethylase (P448-like, class IA, EROD) activities were examined in hepatic microsomes from mice 24 h after acute intoxication. All the halogenated hydrocarbons displayed a marked toxic effect as shown by the significant decrease in cyt. P450 levels (maximum of 76% decrease, with TTCE 753.2 mg/kg) and EROD (maximum of 69% decrease, with PCE 925.4 mg/kg), and to a lesser extent in PROD (maximum of 52.4% decrease, with HCE 3150 mg/kg). Although a general decrease of P450 functions was observed, the toxic effects of TTCE and PCE seem to be preferentially related to P448 forms. PMID- 2576816 TI - Methotrexate resistance in NIH3T3 cells expressing polyoma virus oncogenes. AB - NIH3T3 cell lines expressing different polyoma virus oncogenes were found to differ by almost three orders of magnitude in frequencies of methotrexate resistant (MTXr) cells in single-step selections. Cells expressing the polyoma small T antigen showed the highest frequencies of MTX resistance, whereas cells expressing the polyoma middle T antigen showed the lowest frequencies of MTX resistance. Amplification of the dihydrofolate reductase (dhfr) gene was not a mechanism of MTX resistance in these cell lines. Cells expressing large T antigen also showed a high frequency of MTXr colonies with only two of 20 such colonies showing evidence of marginal (less than threefold) dhfr gene amplification. Cells carrying the cloning vector without an oncogene showed intermediate frequencies of MTX resistance, and in contrast to the oncogene expressing lines, two-thirds of these MTXr colonies showed marked dhfr gene amplification. The results suggest that the plasticity of the genome as measured by frequency or extent of dhfr gene amplification is not increased by expression of either immortalizing or transforming polyoma oncogenes. These oncogenes may, however, influence MTX resistance through epigenetic mechanisms. In addition, there appears to be no relationship between frequency of methotrexate resistance and frequency of dhfr gene amplification. It is clear that mechanisms of resistance other than dhfr gene amplification can be exclusively associated with either very high or very low frequencies of resistance. PMID- 2576815 TI - Thioethers, mutagens, and D-glucaric acid in urine of operating room personnel exposed to anesthetics. AB - Mutagenic hazards related to occupational exposure to nitrous oxide and enflurane was studied in the personnel of five operating rooms using a coupled environmental and biological monitoring approach. The environmental monitoring revealed air concentrations of the two anesthetics exceedings the TLVs by 10-15 fold. These values were correlated individually with the concentrations of the two anesthetics in the expired air of the exposed subjects. The biological monitoring was carried out by determining two parameters associated with mutagen exposure (urinary mutagenicity and thioethers) and a parameter associated with the enzymatic induction (D-glucaric acid) in the urine of exposed and unexposed subjects (N = 64 and N = 37, respectively). The results showed no difference in the two groups for urine mutagenicity and D-glucaric acid, but urine thioethers were significantly increased among highly exposed subjects. PMID- 2576817 TI - Clastogenic effects of benzo[a]pyrene in postimplantation embryos with different genetic background. AB - Certain strains of mice vary in their enzyme inducibility by polycyclic hydrocarbons, i.e., the strain C57 shows high and the strain DBA shows low inducibility of aryl hydrocarbon hydroxylase (AHH) by benzo[a]pyrene (BaP). The effect of this genetically determined difference on the clastogenic response to BaP was studied in 11 day old embryos after transplacental treatment. The four possible crosses, C57 and DBA inter se, C57 X DBA and DBA X C57, were used to determine the influence of the genetic background on the aberration yields in the embryos. Constitutive and induced AHH levels were measured in liver, bone marrow, and placenta of the pregnant females and in their embryos. Enzyme inducibility was high in tissues of C57 dams and in their homozygous or heterozygous embryos. In contrast, induction of AHH activity was low in tissues of DBA females and their homozygous embryos. The high BaP-induced AHH activity found in heterozygous embryos of DBA dams is in agreement with the dominant mode of inheritance for high AHH inducibility. The cytogenetic results showed that the clastogenic response was lowest in homozygous C57 embryos and highest in hybrid embryos independent of the genetic constitution of the dams. Homozygous DBA embryos showed an intermediate aberration yield. The AHH inducibility by BaP did not correlate quantitatively with the induced aberration rates. However, the data suggest that BaP activation in embryonic tissue on day 11 of pregnancy is sufficient to account for the clastogenicity in the fetuses. It is concluded that the genetic endpoint chromosomal breakage is not only determined by the formation of active BaP metabolites but also by genetically controlled detoxification of BaP, repair process, and the rate of transformation of primary DNA lesions into true DNA discontinuities. PMID- 2576818 TI - Effect of beta-adrenergic and serotoninergic agents on the stress-induced behaviour of "learned helplessness" in rats. AB - The phenomenon of "learned helplessness" is characterized by elements of motor, cognitive and emotional deficit, and it is particularly suitable to be used as a "model" of behavioural depression. There is no doubt about the central role of the cerebral noradrenaline and serotonin in the stress-induced behavioural deficit. The effects of two known beta-adrenoceptor agonists--salbutamol and trimetoquinol--and the beta-adrenergic blockers propranolol and compound 3B, with beta-blocking activity equipotent to that of propranolol, were investigated under conditions of "prophylactic" and "therapeutic" administration in rats subjected to stress by modelling of the behaviour of learned helplessness. Among the serotoninergic agents, the effects of 5-hydroxytryptophane and of the inhibitor of serotonin synthesis, parachlorophenylalanine, were studied. The experimental results show a favourable effect on the behavioural deficit, caused by the blocking of the adrenergic transmitter system and by increasing the activity of the serotoninergic system. PMID- 2576819 TI - Active substance from the serum of laying hens and its effect on uterine smooth muscles. AB - Blood serum from laying hens has an excitatory effect on isolated uterine smooth muscles of laying hens. This excitatory effect is not observed for the blood serum of pullets and cocks. After ultrafiltration and gel filtration on Sephadex G25, it was found that the excitatory effect of the blood serum was due to a low molecular substance (m.w. below 5000 Da). The effect of this active substance was found to be inhibited by indomethacin, brufen and SC 19220. The presence of this substance in the serum of laying hens and its contractile effects, which are probably associated with prostaglandin mechanisms of regulation in the uterine smooth muscles, suggests that it is associated in the processes of oviposition in hens. PMID- 2576821 TI - GABA-induced biphasic response in the submandibular ganglion cell. PMID- 2576820 TI - Mechanisms of abnormal endothelium-dependent vascular relaxation in atherosclerosis: implications for altered autocrine and paracrine functions of EDRF. AB - The present studies were performed to determine if abnormal endothelium-dependent vascular relaxation in atherosclerosis is due to decreased production or release of endothelium-derived relaxing factor (EDRF) by atherosclerotic rabbit vessels or if atherosclerotic vessels are less sensitive to the relaxing effects of EDRF. EDRF release was quantified using two approaches, by the response of bioassay detector vessels and also by the activation of guanylate cyclase within cultured endothelial cells. Using these assays, atherosclerotic vessels were found to release significantly less EDRF than normal vessels in response to both receptor- and nonreceptor-mediated stimuli. Relaxations of normal and atherosclerotic vessels to luminally applied EDRF (derived from normal rabbit aortas stimulated by the calcium ionophore, A23187) and nitric oxide, a putative EDRF, were also studied. Atherosclerotic vessels were more sensitive to EDRF than normal vessels, and equally sensitive to nitric oxide. Additional studies performed in organ chambers failed to demonstrate augmented constriction of atherosclerotic vessels in response to acetylcholine in the presence or absence of methylene blue or LY83583, compounds which inhibit the effect of EDRF. We conclude that decreased EDRF release is the principal underlying mechanism responsible for abnormal endothelium-dependent vascular relaxation in atherosclerosis. PMID- 2576822 TI - Treehole breeding of mosquitoes in Nadiad, Kheda district (Gujarat). PMID- 2576823 TI - [Treatment of histamine-dependent allergic dermatoses with a 120-mg terfenadine tablet once a day]. AB - Terfenadine, an anti-H1-selective antihistaminic drug has been used in an experimental clinical study. The effectiveness and tolerance of the compound in the treatment of pruritic dermatitis such as urticaria, atopic dermatitis and topical dermatitis, have been evaluated. Terfenadine, administered in 120 mg tablets in a single daily dose in 30 patients demonstrated a fully satisfactory therapeutic activity and reliability of use. PMID- 2576824 TI - One year under Rivers: drug refusal in a New York State psychiatric facility. PMID- 2576825 TI - HLA antigens and neuroleptic response in clinical subtypes of schizophrenia. AB - The frequency of HLA antigens of A and B loci was examined in a carefully selected sample of 91 schizophrenic patients from central Italy. This population showed no increase in antigens compared with the control group. However, in agreement with previous studies, a slight increase in A1 was observed in the hebephrenic subgroup and, in a lesser extent, an increase of A2 was found in the paranoid subgroup. Although these increases are more prominent when the subgroups are compared and tend to support the case for genetic heterogeneity, they fail to reach statistical significance. Response to neuroleptic treatment was studied in an attempt to further subdivide the clinical subgroups. A1-negative and A2 positive paranoid patients demonstrated a statistical better response to neuroleptics. The findings suggest that schizophrenia should be considered a heterogenous disease and that response to neuroleptics can be employed as an instrument of biological subclassification. PMID- 2576826 TI - A potential mechanism underlying the voluntary suppression of tardive dyskinesia. AB - Many clinicians have observed that patients with tardive dyskinesia (TD) can voluntarily suppress the movements to some extent. The mechanism by which voluntary control is exerted most likely involves peripheral feedback. Quantitative analyses of isometric and isotonic jaw stability were conducted in patients with and without TD to test the general hypothesis that involuntary movements of TD may be brought under voluntary control via one of two receptor mechanisms; muscle length and/or muscle force. Results indicated that in the absence of length feedback patients with TD exhibited significantly greater instability while patients without TD performed within normal limits. This suggests that patients with TD utilized muscle length feedback to suppress motor instability but were unable to utilize muscle force feedback to suppress instability. Implications for the use of laboratory procedures in the measurement and clinical management of TD are discussed. PMID- 2576827 TI - Bilateral kidney rupture with severe retroperitoneal bleeding in polyarteritis nodosa. AB - A patient is described with nontraumatic subcapsular haematomas of both kidneys, complicated by severe retroperitoneal bleeding. A diagnosis of polyarteritis nodosa was reached using renal angiography. Bilateral nephrectomy had to be performed because of uncontrollable renal bleeding. A review of the literature on this complication of polyarteritis nodosa is given. PMID- 2576828 TI - First sporadic case of Hantavirus nephropathy, recognised in The Netherlands. PMID- 2576829 TI - [Health status of schoolchildren under five-day-week school program]. AB - The effect of a five-day educative programme is studied with respect to the health status and morbidity of schoolchildren--from entering VIIth class in the Unified secondary professional school to completion Xth class. The data received are compared with the results from health exam on children, trained on six-day week. The results from the investigation show more favorable dynamics of the chronic, acute and neuro-psychic morbidity, the per cent of those frequently taken ill and is increased the number of healthy schoolchildren. In comparison with the traditional educative organization the five-day week programme has higher prophylactic effectiveness in the health protection of schoolchildren. PMID- 2576830 TI - NHLBI-CNR workshop on 'usefulness and perspectives of bronchoalveolar lavage', Parma, June 13-14, 1988. PMID- 2576831 TI - [Dental trauma: quo vadis]. AB - As figures stand now, dental trauma will in the forseeable future probably surpass dental caries and periodontal disease as the most significant threat to dental health among youth, affecting approximately 50% of schoolchildren before they reach school leaving age. This threat will also be accompanied by just as significant economic consequences. Despite the frequency and severity of dental trauma, little has been done in the dental academic world to examine the cause and effect relationship between, e.g. trauma and later healing complications or acute treatment and the same. Moreover, knowledge about long-term prognosis after trauma is fragmentary. 1989 has been declared by the European Community as children's safety year. Perhaps this year will bring the traumatized child into focus and trigger the research needed to understand the etiology of trauma, its treatment and its consequences. PMID- 2576832 TI - [Biology of traumatic dental injuries]. AB - As it is shown in Tables 1 and 2, there exist large gaps in the experimental basis for the treatment of dental trauma in both the primary and secondary dentitions. It can be seen that approximately 12% of presently accepted therapy are based on experimentally supported treatment principles. This has resulted in a myriad of varying and often conflicting treatment procedures. A systematic investigation of the effect of an acute dental trauma and various treatment procedures on the individual cellular systems would require tremendous scientific manpower. In contrast to this need, the extremely limited research activity in the area of dental trauma is cause for worry. Unless this research area is upgraded nationally and internationally, there is little hope that the random and empirical basis accepted in the treatment of traumatic dental injuries will ever be replaced by a scientifically based set of treatment principles which respect and enhance wound healing in the pulp and periodontium. Only by the fulfillment of this goal will the long-term prospects of traumatized dentitions be improved. PMID- 2576833 TI - [Epidemiology of dental trauma in Denmark: overview and some new points of information]. AB - It is virtually impossible to compare the results of the many studies of traumatic dental injuries, primarily because information is lacking or inaccurate. Another reason, however, is that the basic materials differ substantially. Most studies are based on special groups comprising trauma patients exclusively, and furthermore these are often selected patients, although this fact is not always made clear. In recent years a number of Danish studies have attempted to examine the trauma problem on a population basis. The results of these studies are discussed, a few new results are added and attention is pointed out to problems needing further investigation. PMID- 2576834 TI - [Dental trauma--economic consequences: general observations on insurance possibilities]. PMID- 2576835 TI - [Autotransplantation of premolars in treatment of tooth loss in the anterior maxilla]. AB - The value of autotransplantation of premolars to the anterior region is demonstrated in three cases where respectively one, two and four maxillary incisors were lost due to trauma. It is stressed that a careful analysis should precede this treatment approach. PMID- 2576836 TI - Treatment of traumatic dental injuries: a shift in strategy. PMID- 2576838 TI - Neurotransmitter effects on inhibitory burst neurons in the cat. AB - The present experiment was designed to determine which neurotransmitter influences the burst pattern in the firing of the inhibitory burst neurons (IBN) during vestibular nystagmus. Cats were anesthetized with ether and mounted in a stereotaxic apparatus on a turntable, implanted stimulation electrodes, removed occipital bone and aspirated the vermal part of cerebellum. After the operation ether was discontinued. The recordings took place with the cats in an alert condition created by upper cervical cord transsection, artificial respiration and local anesthesia by infiltrating 0.5% lidocaine into the semilunar ganglions every two hours. We also employed iontophoretic application of the various drugs: GABA, muscimol, glycine, serotonin (5-HT) and bicuculline through seven-barrelled glass micropipettes. GABA or muscimol did not influence nystagmus rhythm, but both chemicals caused strong suppression of burst activities in IBN. Since this inhibitory effect of GABA was suppressed by the simultaneous application of bicuculline, IBNs appear to be controlled by GABAA receptor. Glycine and 5-HT did not change the firing pattern of IBN. Application of bicuculline itself caused an increase of tonic discharges of IBN. These findings suggest that IBN receive inhibitory impulses from the higher GABAergic neurons. PMID- 2576837 TI - [Studies on the mechanism of blood pressure variability]. AB - Blood pressure variability has been known in the cardiovascular clinic for a long time. The mechanisms of the variations are largely unknown; it was the aim of the present work to approach this question. In a first group of studies, the role of the adrenergic receptors was examined. The results have shown that the adrenergic system does not play an important role in this phenomenon as administration of beta and of alpha blocking agents is unable to diminish the amplitude of the blood pressure variations; this was confirmed by other studies showing no correlation between blood pressure variability and the response to sympathetic function tests. However, there was a positive correlation with the level of blood pressure. In a second part, the role of the cholinergic system was investigated; atropine was found to diminish, both in dogs as in men, the amplitude of blood pressure variability. No decrease of blood pressure variability was seen with calcium antagonists. Thus, blood pressure variability is depending on the level of blood pressure and cholinergic activity; since these mechanisms only explain part of blood pressure variability, further research will be needed to unravel this challenging question. PMID- 2576839 TI - Localization and origins of calcitonin gene-related peptide containing fibres in the vestibular end-organs of the rat. AB - The distribution, origin and fine structure of nerve terminals immunoreactive to calcitonin gene-related peptide (CGRP) were investigated in the vestibular end organs of the rat by means of immunocytochemistry. Dense plexus of CGRP-like immunoreactive (CGRPI) fibres were observed just beneath the sensory epithelial layers of the ampullary crista of the semicircular canal, and utricular and saccular maculae of the otolith organ. Some CGRPI fibres left the plexus to enter the sensory epithelial layer. Parasagittal transection of the brain just medial to the cochlear nucleus revealed the presence of a few CGPRI fibres in the vestibular end-organs ipsilaterally, indicating that these fibres originate in the central nervous system. A combination of retrograde tracing and immunocytochemistry was then used to identify the origins of CGRPI fibres found in the vestibular end-organs. After injection of fast blue dye (FB) into the vestibular cistern, CGRPI neurons in the area dorsolateral to the genu of the facial nerve were labelled by FB bilaterally. The present ultrastructural study has revealed that most of the CGRPI fibres in the vestibular end-organs form direct contacts with afferent nerve terminals which surround type I vestibular sensory cells. PMID- 2576841 TI - Structure and absolute configuration of two stereoisomers of alpha,alpha' [iminobis-(methylene)]bis(3,4-dihydro-2H-1-benzopyran-2- methanol) hydrobromide. AB - alpha,alpha'-1,1'-Bis(3,4-dihydro-2H-benzopyran-2-yl)-2,2'-iminodieth anol hydrobromide. (I) C22H28NO4+.Br-, Mr = 450.37, orthorhombic, P2(1)2(1)2(1), a = 5.1278(1), b = 13.1699(6), c = 30.858(2) A, V = 2083.9(2)A3, Z = 4, Dm = 1.44, D chi = 1.436 Mg m-3, lambda(Cu K alpha) = 1.54178 A, mu(Cu K alpha) = 2.915 mm-1, F(000) = 936, room temperature, final R = 0.054 for 2086 observed reflections. (II) C22H28NO4+.Br-, Mr = 450.37, orthorhombic, P2(1)2(1)2(1), a = 5.1292(2), b = 13.1764(9), c = 30.847(3) A, V = 2084.8(3)A3 lambda(Cu K alpha) = 1.54178A, mu(Cu K alpha) = 2.915 mm-1, F(000) = 936, room temperature, final R = 0.054 for 2676 observed reflections. The two structures are mirror images and the central C--C- N--C--C chain adopts the anti-periplanar-synclinal conformation. The active beta 1-selective adrenergic receptor blocker [isomer (I)] has the S,R,R,S absolute configuration while the inactive isomer (II) has the R,S,S,R configuration. Endless chains are formed by (N-)H...Br hydrogen bonds in the a direction and by (O-)H...Br hydrogen bonds in the b direction. PMID- 2576840 TI - [Tooth mutilation in the scope of ritual mutilation]. AB - Study of the motivations and description of ritual dental mutilation techniques. All initiation rites have one thing in common: blood must flow. Some tribes give the choice between circumcision or the pulling of one or several teeth. Proposal of analysis of the transfer in modern life of the primitive "obsession of the borders" described by ethnologists. PMID- 2576842 TI - [Neuromodulators in otorhinolaryngology]. AB - We comment on basic principles on neuromodulators and some aspects dealing with the new information that these substances may bring to the knowledge of neurobiology in ENT. PMID- 2576844 TI - [New aspects of beta-blocker therapy. Pharmacological findings and therapeutic relevance. Satellite symposium of the European cardiology congress in Vienna]. PMID- 2576843 TI - Growth inhibition and induction of phenotypic alterations by L-histidinol in B16 mouse melanoma cells. AB - L-Histidinol, a histidine analog was recently shown to be an inducer of differentiation in the promyelocytic cell line HL-60. In the present study we show that L-histidinol inhibits the growth of B16 melanoma cells in vitro. Growth inhibition is accompanied by phenotypic alterations that include a marked increase in the activities of NADPH cytochrome c reductase and gamma glutamyl transpeptidase, lipid accumulation and cell enlargement. These phenotypic alterations are similar to those induced by other chemical inducers of differentiation in melanoma cells. PMID- 2576845 TI - [Cardiology meeting: mechanism of action and effects of modern beta blockers]. PMID- 2576846 TI - Replication of SV40 in vitro using proteins derived from a human cell extract. AB - In the presence of large T antigen and plasmids containing a functional origin of replication, extracts from a human cell line will support multiple rounds of simian virus 40 (SV40) replication in vitro. Fractionation of this extract has led to the identification of several factors, some of which have been purified to homogeneity. The characterisation of these proteins has led to the separation of SV40 replication in vitro into multiple stages. Two proteins, the cell cycle regulated proliferating cell nuclear antigen and replication factor-C, have been shown to be essential for coordinating leading and lagging strand synthesis in this system. Another protein, replication factor-A, is a multi-subunit protein of 70, 34 and 11K (K = 10(3) Mr) polypeptides which, because of its high affinity for DNA, is thought to function as a eukaryotic single-stranded DNA binding protein. Interactions between other cellular factors are also described that effect the initiation of DNA replication, but are not required in a more purified system. In addition a model for a hypothetical replication fork is described, which suggests a role for both alpha- and delta-polymerases in this system, and may be applicable to higher eukaryotes. PMID- 2576847 TI - DNA replication and cell cycle control in Xenopus egg extracts. AB - Aspects of the regulation of DNA replication and mitosis have been studied using a cell-free extract of Xenopus eggs. The extract is characterized by repeated cycles of DNA replication and mitosis, which are accompanied by periodic synthesis and degradation of cyclins as well as fluctuations in the level of Histone H1 kinase activity. DNA replication in this system is dependent upon the formation of a nucleus. However, while nuclear structures are clearly required for initiation, a complete nuclear membrane does not appear to be necessary. Indirect immunofluorescence and DIC microscopy indicate that nuclear reformation from chromosomes occurs asynchronously around individual chromatids. Lamin polymerization, biotin-11-dUTP incorporation and association of polymerases with chromatin occur before membrane formation is complete. S phase nuclei are typified by the co-distribution of both anti-DNA polymerase alpha and anti-PCNA antibodies as discrete spots of fluorescence which align the chromatin. However, as DNA replication is terminated, PCNA fluorescence fades and DNA polymerase alpha dissociates from the chromatin and is redistributed throughout the nucleoplasm. By inhibiting DNA replication with aphidicolin, both DNA polymerase alpha and PCNA remain associated with the chromatin throughout prolonged incubation. Under these conditions mitosis is delayed by up to 70 min, although both the general rate of protein synthesis and more importantly the rate of cyclin synthesis and histone kinase activation are unaffected. Upon nuclear envelope breakdown and lamin dispersal, cyclins degrade; however, no chromosomes are formed, and both PCNA and DNA polymerase alpha remain associated with the chromatin. Also, histone kinase activity is maintained at elevated levels. PMID- 2576848 TI - Localization of human placenta lysyl oxidase on human placenta, skin and aorta by immunoelectronmicroscopy. AB - Polyclonal antibodies to human placenta lysyl oxidase (Kuivaniemi et al., 1984) were used to localize the enzyme at ultrastructural level in human placenta, skin and aorta, by using the indirect immunogold method. The antibodies were tested on thin sections of tissues fixed and embedded in various experimental conditions. With all methods employed, the immunoreaction was always positive on collagen fibers in all tissues examined, independently of the age of the subjects. In placenta, the reaction was also slightly positive on matrix microfilaments and cells. In dermis, fibroblasts and elastin were scarcely positive in a normal 5 day-old child, in a child with skin hyperelasticity, and in two babies with osteogenesis imperfecta type II; whereas they were negative in two 16 and 40 year old normal subjects. In aorta, the immunoreaction was always positive on collagen, scarcely positive on cells and on elastin of a 24 week-old fetus, of a normal child, and of two babies who died of complications associated with O.I. type II; on the contrary, the reaction was negative on cells and elastin fibers of a 16 week-old fetus, and of a normal 19 year-old girl. When present on elastin, gold particles were localized mostly inside the fibers. Contrary to what was observed by Kagan and coworkers on bovine aorta by using antibodies against aortic lysyl oxidase (Kagan et al., 1986), no specific localization of gold particles could be observed on or adjacent to the elastin/associated microfibrils. The results indicate that antibodies raised against placenta lysyl oxidase recognize collagen-associated as well as elastin-associated epitopes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576849 TI - [Somatostatin in the emergency treatment of upper digestive hemorrhage in patients with portal hypertension]. AB - During a 2-yr period 15 patients (17 episodes) with variceal bleeding (VB) and 7 with cirrhosis and acute gastroduodenal haemorrhage (GDH) received intravenous somatostatin (250 mcg per hr after a bolus of 250 mcg). Initial control of bleeding was achieved in 13 (76%) with VB and in all with GDH. Three of the 4 patients with VB and 2 with GDH who rebled during treatment were controlled increasing the infusion to 500 mcg/hr. Patients with VB received somatostatin for 24 hrs, time selected for initiating injection sclerotherapy, and those with GDH for 48-72 hrs. At 24 hrs 71% of patients with VB and all with GDH were free of bleeding. Combining different therapies VB was controlled in 16 of the 17 episodes (94%) with only one death. No complications were observed in any of the 22 patients treated. PMID- 2576850 TI - [Advances in the knowledge of peptic-acid dependent diseases]. PMID- 2576851 TI - [Synthesis of new derivatives of 5H-furo[3,2-g][1]benzopyran-5-one with potential beta-adrenolytic activity]. AB - With the purpose of obtaining new compounds with antiarrhythmic activity, nine novel aminoalkanol derivatives of 5H-furo[3,2-g] [1]benzopyran-5-one were synthetized. In pharmacological studies, compound IX proved to display strong antiarrhythmic action, which in chloroform-induced arrhythmia was stronger from that of propranolol at three times lower acute toxicity. PMID- 2576852 TI - The effect of ACTH-treatment on gastric acid secretion and gastric regulatory peptides in young pigs. PMID- 2576853 TI - [Opioid analgesia during extracorporeal shockwave lithotripsy of gallstones]. AB - Gallstone lithotripsy is a new and noninvasive therapeutic option for approximately 20% of patients who harbor cholesterol gallstones. Technologically advanced second-generation lithotripters such as the Dornier MPL 9000 device have greatly simplified biliary lithotripsy with a consecutive reduction in anesthetic requirements. Despite these technical improvements, patients still can experience considerable pain and discomfort during biliary ESWL. Due to its relatively predictable pharmacokinetic profile and its short duration of action, alfentanil appeared to be a suitable drug for pain relief during stone fragmentation. In order to analyze the degree and distribution of pain during gallstone lithotripsy and to evaluate pain control by alfentanil, 44 consecutive patients (ASA I-II) with no previous ESWL therapy were studied. Pain intensity and degree of opioid induced sedation during shock wave application were evaluated according to 5 point verbal scales that ranged from 0 = no pain to 4 = unbearable pain and 0 = patient awake to 4 = patient asleep. All patients were treated while in the prone position and received oxygen at 6 l/min. After stone focusing, an alfentanil infusion at an initial rate of 2.5 micrograms/kg min was started. Single shock waves were released as test shocks after approximately 2 min. If they were well tolerated, stone fragmentation was begun. If not, more alfentanil was allowed to accumulate until continuous treatment was tolerated. Further in- or decreases of the infusion rate were titrated according to patient response. Registered variables included the required alfentanil loading dose, maintenance and total doses, and the applied shock wave energy approximated by multiplication of shock wave number and voltage squared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2576854 TI - [Neuromuscular blockade using vecuronium in dermatomyositis]. AB - The significant features of neuromuscular blockade with vecuronium in a patient with dermatomyositis are described: vecuronium 0.08 mg/kg resulted in 90%, 0.12 mg/kg in 100% neuromuscular blockade. In contrast to claims made in some previous publications, dermatomyositis did not produce increased sensitivity to vecuronium. Onset time and duration of action were also within normal limits in our patient. Time of spontaneous recovery until antagonism with neostigmine was markedly prolonged, but the dermatomyositis was only one of various possible explanations. Although there are potential hazards in the use of neostigmine in patients with dermatomyositis, antagonism of the neuromuscular block with 2 mg neostigmine was without problems in our patient. Our data support recent suggestions to reconsider the implications of dermatomyositis for anesthesia. PMID- 2576855 TI - Purification of soluble guanylate cyclase enzyme from human platelets. AB - Soluble guanylate cyclase enzyme was purified from human platelets. The soluble fraction of the lysed platelets was sequentially chromatographed over DEAE sepharose, GTP-agarose and HPLC size-exclusion columns. About 0.1 mg of purified enzyme could be obtained from 2000 ml of platelet rich plasma. The purified enzyme had the specific activity of 205 nmoles cGMP/mg/min with Mn2+ as cofactor. The enzyme eluted at the 160,000 daltons position from the size-exclusion column. Electrophoresis in the presence of sodium dodecyl sulfate under reducing conditions revealed two subunits of 83,000 and 71,000 daltons respectively. PMID- 2576856 TI - Interaction of erythrocyte transglutaminase with calcium ions. AB - We have investigated the interaction between calcium ions and erythrocyte transglutaminase and the enzyme activation. The binding involves both high and low affinity sites, but only the former ones are relevant for activation. The binding of calcium and the activation are modified by treatment with NBD-Cl and with PLP suggesting the presence of cysteine and lysine residues at the high affinity binding sites. The interaction of the enzyme with calcium is not calmodulin dependent and is easily detected as a shift in electrophoretic mobility in the presence of SDS. PMID- 2576857 TI - The homeobox in vertebrate development. PMID- 2576858 TI - Neurite guidance molecules. PMID- 2576860 TI - Drosophila development. PMID- 2576859 TI - Caenorhabditis elegans development. PMID- 2576861 TI - [Interruption of early viremia in patients with epidemic hemorrhagic fever]. AB - Kinetic changes of viremia were observed in 287 patients with epidemic hemorrhagic fever (EHF) in whom ribavirin was administered with a double blind random controlled study by means of virus isolation, indirect immunofluorescence technique and ELISA. The positive rate of viremia was 79.7%, and the positive rate of EHF IgM was 85.0% before treatment. Viremia could be interrupted by ribavirin. In the ribavirin group, the positive rate of viremia decreased, duration of viremia was shortened, viral antigen products, viral titer and EHF IgG level were reduced as compared with the control group. These showed that viremia is very frequent in patients in the febrile phase, and ribavirin is an effective antiviral drug in treatment of EHF during the febrile phase. Dosage of the drug and the course of treatment are discussed. PMID- 2576862 TI - The role of coated vesicles in recycling of synaptic vesicle membrane. AB - The uptake of extracellular tracers into synaptic nerve terminals has been a phenomenon of persistent interest. Uptake is into synaptic vesicles, hence vesicles spend part of their life in continuity with the plasma membrane, as expected if exocytosis underlies the quantal discharge of neurotransmitters. However, exactly how or when synaptic vesicles acquire extracellular tracers has not been unambiguously determined. Two schools of thought have developed, one holding that vesicles acquire tracers directly via a reversible exo/endocytotic sequence in which they consistently maintain their biochemical identity during their transient continuity with the plasma membrane, the other holding that synaptic vesicles acquire tracers indirectly, via the formation of clathrin coated vesicles which are spatially and temporally separate from exocytosis and reverse a temporary loss of the vesicles' individual identity upon merger with the plasma membrane. Efforts to distinguish between these two alternatives have generated an interesting diversity of electron microscopic experiments, many of which are reviewed here. However, definitive determination of which view is correct may ultimately require direct visualization of synaptic vesicle turnover in living nerve terminals. To this end, we here review the results of visualizing endocytosis in tissue cultured cells, where light microscopy can provide sufficient resolution to reveal membrane dynamics in living cells. This has allowed visual discrimination of two different types of endocytosis, one clathrin mediated (coated vesicle formation) and the other actin-mediated (macropinocytosis). Current work is also reviewed which aims at determining experimental methods for inhibiting each type of endocytosis selectively. Hypertonicity and severe cytoplasmic acidification turn out to inhibit coated vesicle formation, while cytochalasin D and mild cytoplasmic acidification selectively inhibit macropinocytosis. Applied to nerves, these various treatments affect synaptic vesicle turnover in a manner that supports the notion that synaptic vesicle membrane recycles via the "indirect" route of coated vesicle formation. PMID- 2576863 TI - Intracellular mechanism of neurotransmitter-induced modulations of voltage dependent Ca current in snail neurons. AB - This paper reviews our work on the modulation of voltage-dependent Ca currents in identified snail neurons. Ca currents of snail neurones are enhanced or decreased by neurotransmitters. Serotonin and acetylcholine enhance the Ca current of identified neurons, the effect of serotonin being mediated by cGMP and cGMP dependent protein kinase. Cholecystokinin (CCK8) and dopamine both decrease the Ca current of identified neurons. The effect of CCK8 is irreversible and involves the activation of protein kinase C. The dopamine-induced decrease in Ca current is reversible and involves an alpha 40 subunit of a snail G protein immunologically and functionally related to alpha o of mammalian brain. PMID- 2576864 TI - Neurotransmitter release: the neuromuscular junction. Bruno Ceccarelli Memorial Symposium. A satellite of the 12th European Neuroscience Meeting. Milan, September 2-3, 1989. Proceedings. PMID- 2576865 TI - [An electron microscopic study of viral infected peripheral mononuclear cells in epidemic hemorrhagic fever]. AB - Ultrathin sections of peripheral blood cells from 7 patients of early stage epidemic hemorrhagic fever (EHF) were reexamined under transmission electron microscope. Virus particles were found in the cytoplasmic vacuoles of mononuclear cells from two patients. The morphology and morphogenesis of the matured virus were identical with those of Hantaan virus of the Bunyaviridae family. Additionally, abnormal aggregations of tubuloreticular structure (TRS) were sometimes encountered in the dilated cisternae of endoplasmic reticulum in the lymphoid cells regardless of whether there are virus particles present in the cytoplasm. PMID- 2576866 TI - Efficacy of inactivated vaccine containing cyto-hemagglutinin against epidemic hemorrhagic fever in rabbits. AB - Using the Z-10 strain of epidemic hemorrhagic fever virus (EHFV) as seed, and the primary cell of Meriones unguiculatus kidney tissue as incubation cell, a propiolactone inactivated epidemic hemorrhagic fever (EHF) vaccine was prepared, according to a similar procedure required for the production of biological products such as the Japanese B encephalitis vaccine. Besides the EHFV antigen detected by ELISA or reversed passive hemagglutination test (RPHA) as were used for the formalin inactivated vaccine, higher titres (1:128-1:1024) of EHFV hemagglutinin antigen was also detected in this EHFV vaccine. Immunization with twice intramuscular injection of this vaccine produced high titred (1:20-1:160) neutralizing antibody and low titred (1:10-1:20) hemagglutination antibody, in addition to the immunofluorescence (IF) and reversed passive hemagglutination inhibition (RPHI) antibodies. These results indicated an apparent difference in the immunogenicity between the beta-propiolactone and formalin inactivated EHF vaccines. With the approval of the Ministry of Health, human test is now underway in this laboratory. PMID- 2576867 TI - Molecular approaches to vertebrate limb morphogenesis. AB - It has long been proposed that concentration gradients of morphogens provide cues to specify cell fate in embryonic fields. Recent work in a variety of vertebrate systems give bona fide evidence that retinoic acid, the biologically active form of vitamin A, is a candidate for such a morphogen. In the developing chick wing, for example, locally applied retinoic acid triggers striking changes in the pattern along the anteroposterior axis. Instead of giving rise to a wing with the normal 234 digit pattern, wing buds treated with retinoic acid develop a 432234 mirror-image symmetrical digit pattern. For this review, we focus on three aspects of limb morphogenesis. (1) We summarize the experimental evidence supporting the notion that retinoic acid is a candidate morphogen. (2) Limb buds contain high levels of cellular retinoic-acid-binding protein (CRABP). Using order of magnitude calculations, we evaluate how the concentration of CRABP might affect the occupancy state of the retinoic acid receptor. (3) We discuss the spatio-temporal expression pattern of homeobox-containing genes in the developing limb and speculate about the possibility that retinoic acid influences the pattern of expression of homeobox genes. PMID- 2576869 TI - Control of mosquito breeding in wells by the application of expanded polystyrene (EPS) beads. PMID- 2576868 TI - Mosquito breeding in rice fields and its role in malaria transmission in Mandla district, M.P. AB - A study of the breeding of mosquitoes in the rice field agro-ecosystem was carried out in Mandla district during 1987 and 1988. Results revealed that mosquito breeding commences in July and ends in October. Mosquito breeding in rice fields is inversely proportional to the distance from village. A. culicifacies breeds in rice fields up to a plant height of 20 cm and then gradually declines and becomes scarce, and is taken over by A. theobaldi and A. splendidus. A. fluviatilis breeds in irrigation channels almost throughout the rice growing season. There were a large number of other mosquito breeding sites which increased enormously with the onset of rains. The precise role of rice fields in maintaining high malaria transmission could not be established but the rice field agro-ecosystem contributed significant vector populations. PMID- 2576870 TI - [Madrepore as a bone filler]. AB - The authors studied the behaviour of the porite type coral which has been previously implanted in man in order to get a reparation of osseous and parodontal defects. The histomorfological exam (at the optical microscope, SEM and X-Ray microscope) of a non decalcified bioptic piece, which had been obtained with an appropriate instrument, shows a deposition of neoformed bone around the coral. Six months after the implantation the tissue was stable without any osteoclasts in activity; even the implanted coral grains had not been attached by them. The Authors agree with most of the statements made by Souyris et Al., but they do not believe in the total substitution of the coral with the bone, at least not in short terms: therefore further scientific works will be necessary to clear this point. PMID- 2576871 TI - A case of bulimia successfully treated by cue exposure. AB - In the present case-study, a 22-year-old female patient with a 7-year history of bulimia nervosa was treated by cue-exposure. During cue-exposure sessions the relationship between CS (stimuli associated with binge-eating behaviour) and UCS (the sensations related to the intake of binge food) was broken. As predicted, the patients' craving for food declined within as well as between cue exposure sessions and a radical decrease in the frequency of binge-eating persisted for at least nine months. Although during the therapy no explicit attention was paid to the patient's low mood and irrational self-talk, mood was improved and beliefs were less irrational after cue-exposure and at the follow-ups. The data suggest that cue exposure may be an effective part of the treatment of bulimia nervosa. PMID- 2576872 TI - Molecular analysis of a novel glutamine synthetase of the anaerobe Bacteroides fragilis. AB - The nucleotide sequence of a 2777 bp DNA segment containing the Bacteroides fragilis glnA gene was determined. The B. fragilis glnA open reading frame of 2187 bp encoded a glutamine synthetase (GS) subunit of 729 amino acid residues with a calculated Mr of 82,827. The apparent Mr of the GS subunit determined by SDS-PAGE was approximately 75,000. A single mRNA transcription start point was identified upstream of the B. fragilis glnA open reading frame. The B. fragilis GS subunit is approximately 270 and 400 amino acids longer than the GSI and GSII subunits, respectively, of other prokaryotes and eukaryotes. The GSI and GSII holoenzymes are dodecamers and octamers respectively, whereas the GS of B. fragilis is a hexamer. Although GSI and GSII subunits show amino acid similarity in five conserved regions, this similarity is not strongly conserved in the B. fragilis GS. The GS of B. fragilis is not regulated by adenylylation and lacks the adenylylation site. It also lacks the Trp residue associated with the active site in GSI and GSII enzymes from other prokaryotes and eukaryotes. PMID- 2576873 TI - Restriction fragment polymorphism in mitochondrial DNA of Cryptococcus neoformans. AB - The restriction patterns of mitochondrial DNA from 20 isolates of the two varieties of Cryptococcus neoformans were compared. The patterns exhibited extensive heterogeneity among the isolates regardless of their serotype or varietal status. Hybridizations with cloned fragments of the conserved cytochrome oxidase gene from Saccharomyces cerevisiae exhibited at least seven patterns among the 20 isolates. There were, however, similarities in the restriction patterns among isolates within the same serotype that were not shared by isolates of other serotypes. Intra-varietal similarities were observed in the restriction patterns among the isolates of C. neoformans var. neoformans which were not present in the restriction patterns among the isolates of C. neoformans var. gattii. Hybridization of some cloned mitochondrial DNA fragments to total DNA digests of various isolates revealed polymorphic as well as variety-specific patterns of homology. These findings agree with the antigenic heterogeneity among the isolates and support the current taxonomic classification of C. neoformans into two varieties. PMID- 2576875 TI - [Tolerance and tachyphylaxis during the long-term local treatment of different forms of glaucoma with Arutimol]. PMID- 2576874 TI - Production of the fimbrial adhesin 987P by enterotoxigenic Escherichia coli during growth under controlled conditions in a chemostat. AB - The effects of growth conditions on the production of 987P fimbriae by the enterotoxigenic Escherichia coli strain 1592 were examined in steady state chemostat experiments at different specific growth rates. The amount of fimbriae produced by fimbriate cells (P+) was dependent on the specific growth rate (mu). Under aerobic growth conditions fimbriae production increased with higher mu values till mu = 0.40 h-1 and decreased again at mu values close to mu max (0.48 h-1). Under anaerobic growth conditions the maximal production was comparable to that under aerobic growth conditions, and was also maximal close to mu max (0.16 h-1). Phase variation, measured as the percentage of fimbriate cells in a particular population, was independent of mu. The composition of the growth medium influenced both phase variation and overall production of fimbriae. A shift from minimal to a complex medium induced a rapid reduction in the amount of fimbriae per P+ cell and a slower reduction in the percentage of P+ cells. A shift from complex to minimal medium resulted in an increase in the percentage of P+ cells and a constant amount of fimbriae per P+ cell. The frequency of the phase switch was calculated for different growth conditions. The frequency of the P+----P- switch between two steady states was 2.7 x 10(-2). In batch culture the frequency of the P(-)----P+ switch was minimally 2.9 x 10(-2). The results indicate that phase variation and the production of 987P fimbriae by fimbriate cells are under independent physiological control. PMID- 2576876 TI - [The therapeutic efficacy of Arutimol in open-angle glaucoma]. PMID- 2576877 TI - [Morphologic and functional aspects of cells of the "diffuse neuroendocrine system" of the airways]. PMID- 2576878 TI - [Endocrinology of cryptorchidism]. AB - The testicular descent into the scrotum depends on a series of complex endocrine and mechanical interactions. The first stage or transabdominal that occurs during the first 3 months of gestation is probably produced by the differential growth of the fetus and is believed to be mediated by the Mullerian inhibiting hormone. The second stage or transinguinal migration that occurs during the 8th month of gestation is a complex event depending on the interaction between the hypothalamic-pituitary-testicular hormonal axis and mechanical factors as gubernaculum, intra-abdominal pressure, epididymis. This stage is believed to be androgen dependent. Although hormonal involvement in testicular descent appears clear-cut, there is nevertheless some discrepancy in the literature as to whether cryptorchid children show abnormalities in their hypothalamic-pituitary testicular axis. Certainly cryptorchidism is a syndrome with various causes. Few cases show primary anatomical abnormalities or are associated to complex congenital anomalies or to clear hormonal defects. Most cases do not recognize an evident cause and an endocrinological abnormality has been suggested. A deficiency in LH and testosterone secretion has been reported in the cryptorchid child. PMID- 2576879 TI - Calmodulin and the transmitter release at the neuromuscular junction. Contradictory results obtained with trifluoperazine. AB - Calmodulin seems to be strongly involved in the process of transmitter release. By activating a specific proteinkinase system, calmodulin could initiate the phosphorylation of some axolemal or vesicular protein, thus triggering the exocytosis of the synaptic vesicles and the transmitter release. Under these conditions it was to be expected that a calmodulin blocking agent such as trifluoperazine, used in appropriate concentrations for this effect, should block the transmitter release. Contradictory results determined us to reexamine the question under extended experimental conditions. Our data suggest that calmodulin could both activate and block the transmitter release through probably different mechanisms. PMID- 2576880 TI - Modulation of protein degradation in mammalian cells by ligands and stress. AB - Two types of environmental effect on intracellular proteolysis in mammalian cells are surveyed. One is the effect of products on the in vivo half-lives of certain enzymes. The other is the effect of stress on the degradation of cellular proteins. The degradation rates of glutamine synthetase (GS), ornithine decarboxylase (ODC) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase are markedly accelerated by their products. The ligand binding sites responsible for the product-accelerated degradation of the enzymes are unknown. In all three cases the labilizing effect of the product molecule is not due to its attachment to the catalytic site. The modes of action of product molecules on GS and ODC degradation have many features in common. Heat shock or other stress cause damage to cellular proteins and induce the synthesis of a small set of heat shock proteins (hsp). Many stressing agents or conditions also accelerate the breakdown of cellular proteins. Current evidence supports the view that the ubiquitin system is responsible for the disposal of aberrant proteins formed by stress. Many observations support the hypothesis that hsp gene expression is induced when abnormal proteins are produced in amounts that exceed the cell's degradative capacity. However, it is still not clear how aberrant proteins induce hsp. PMID- 2576881 TI - Proteolysis induced by metal-catalyzed oxidation. AB - Many enzymes are now known to be subject to site-specific, covalent modification mediated by activated oxygen species. Oxidatively modified enzymes generally lose catalytic activity, gain carbonyl groups in their side chains, and become susceptible to proteolytic degradation. Thus, oxidative modification is one of the covalent alterations which marks proteins for degradation. This degradation is mediated by specific intracellular proteinases which degrade only the modified proteins. One can then view the turnover as occurring in two distinct steps: 1) Metal-catalyzed oxidative modification marks the protein for degradation. 2) The marked protein is degraded by a specific proteinase. Utilizing a model metal catalyzed oxidation system (ascorbate/iron/oxygen) studies on bacterial glutamine synthetase revealed several functional and structural changes. Analysis of the time courses of these changes established correlations between specific structural alterations and increased susceptibility to proteolytic degradation. PMID- 2576882 TI - Regulatory peptides in the thyroid gland. PMID- 2576883 TI - Research in rehabilitation. Austria. PMID- 2576884 TI - [Sipple's syndrome. Review of the literature and personal case load]. AB - A family with Sipple's syndrome was studied over three generations. The syndrome is transmitted as a dominant autosomic hereditary trait with high penetrance and varying expressiveness. Our series include 13 patients of three generations: 1) husband and wife who were 1st degree cousins; 2) 4 sisters and 1 brother; 3) 5 sisters and 1 brother. In the first generation we did not find any sign that could be related to the syndrome, in the second generation 2 thyroid carcinomas and a pheochromocytoma were present, and in the third one 2 sisters had these neoplasias, one pheochromocytoma and the other thyroid cancer, another one had marfanoid habitus and the fourth one had pheochromocytoma. This series includes 11 subjects of the second and third generation; the Sipple's syndrome was present in 7 females. The incidence of the syndrome was 63.8% and present only in female subjects. The high incidence rate could be caused by the strict relation between the grandparents. The diffusion of this pathology may be related to the high penetrance of the gene(s) involved whereas the clinical variations may be interpreted to the variable expressiveness and, even more so, as evidence that the other manifestations of the syndrome may occur later in time. PMID- 2576885 TI - [The growth hormone/somatomedin C system from the first years of life to young adulthood. Physiological aspects and physiopathologic involvement in diabetic syndrome]. AB - The growth hormone (GH)/somatomedin-C (Sm-C) endocrine system plays a fundamental role in human anabolism. Whereas from a physiological point of view GH conforms to the classic hormone behaviour, Sm-C appears to follow a peripheral and local pattern of action with autocrine or paracrine involvement. The hormonal GH system interacts with the functional pattern of insulin and other hormones, and in addition with entire maturation process. On the basis of several reports, the puberal age seems to represent the first real "maturative-tumultuous" event managed by the operative GH/Sm-C system. It is thus possible to hypothesise that alterations to this system, as found in dysmetabolic diseases (e.g. diabetes), may either be seen as a cause or consequence of the disease process. It can therefore also be supposed that such alterations may interact with the development of the entire organism, above all when they occur during the delicate puberal phase. PMID- 2576886 TI - [Effects of somatostatin peridurally administered in the treatment of postoperative pain]. AB - Somatostatin (SMS), a hormone extensively found within the CNS, has shown to have a powerful analgesic effects administered either via the epidural or subdural route. The aim of the present study was to evaluate the efficacy of SMS administered epidurally compared with placebo, for the treatment of post operative pain in patients receiving epidural anaesthesia for surgery. Of the 86 patients observed, 58 entered the study and were randomized to receive either SMS or placebo in a double blind fashion. They were also divided into 3 groups according to the site of the operation (group A: procto-anal; group B: inguino crural; group C: other), 28 of them receiving SMS and 30 placebo. The post operative pain evaluation was obtained via VAS at the moment of request of treatment (basal) and after an hour. Twenty-eight of the 86 observed (32.5%) didn't complain of pain that necessitated analgesic treatment. A statistically significant difference in reduction of intensity of pain was observed in the somatostatin treated group (6.42 +/- 0.37 vs 3.64 +/- 0.59) and in the somatostatin treated subgroup A and B (6.4 +/- 0.4 vs 3.8 +/- 0.7 and 6.3 +/- 0.8 vs 3.0 +/- 0.6 respectively). No adverse reactions of any kind were observed. SMS has shown to be a safe and effective drug, reducing by 50% the intensity of pain in patients undergone procto-anal or inguino-crural surgery. PMID- 2576888 TI - [The psychoprophylactic importance of treatment with depot neuroleptics in schizophrenia]. AB - The authors refer to the analysis of a sample of 104 schizophrenic inpatients treated with depot neuroleptics. The study relates to the duration of the illness, the number of admissions, social and professional integration and the patient's and family attitude to the long term treatment. The analysis and the interpretation of the data allow the estimation of the efficiency of the depot neuroleptics in outpatient schizophrenia reflected by social integration, the prophylaxis of recurrences and severe developments, the stabilization of symptoms and shortening of hospitalization span. The psychoprophylactic significances of the treatment with depot neuroleptics in schizophrenia confirms chemical correlations with pharmacological data and brings into relief the unsubstituting value of the fashion of psychoprophylactic and recovering care delivery on the background of existential relationships. PMID- 2576887 TI - [Biological markers in the accurate diagnosis of chronic alcohol intoxication. The significance of gamma-glutamyl transpeptidase]. AB - The late diagnosis of severe alcoholism--often after the onset of somatic complaints and the appearance of psychic disorders needs extensive research able to identify new objective clinical and paraclinical markers to allow early and accurate identification of alcoholism also after various periods of abstinence. The scores obtained are the consequence of alcohol abuse and not of nutritional deficiencies or some other associated visceral-humoral sufferings. The authors underline the significance of gamma-GTP in assessing early severe alcoholism state and the necessity and importance of finding certain specific biological markers--early and sensitive for etillic intoxication--that would considerably simplify the manner of diagnosis and an efficient therapy. The identification of certain significant and specific markers before the onset of visceral-humoral disorders would improve the psychoprotective measures before the onset of tolerance and withdrawal--determinant factors of severe etillic intoxication. PMID- 2576889 TI - [Current developments in the pharmacology of the dopaminergic receptors. III]. PMID- 2576890 TI - Effect of alpha-adrenergic receptor blockers on the vulnerability of cat heart to ventricular fibrillation. AB - Recently, alpha-adrenergic receptors have been implicated in the precipitation of arrhythmias associated with myocardial ischemia and reperfusion. The present investigation has been undertaken to study the effect of alpha-adrenoceptor antagonists on electrically induced ventricular fibrillation. The effect of ventricular fibrillation on the alpha-adrenergic receptor population in myocardium and its modification by phentolamine pretreatment has also been investigated. Phentolamine and prazosin raised the ventricular fibrillation threshold significantly. However, yohimbine was protective at high doses only (3 and 5 mg/kg). There was no change in alpha-receptor population and affinity after ventricular fibrillation. Cyclic AMP levels increased in the fibrillating myocardium. Pretreatment with phentolamine did not prevent the decrease in blood flow observed after electrically induced ventricular fibrillation. It is concluded that alpha 1-adrenergic receptor blockade is protective against ventricular fibrillation in cats. PMID- 2576891 TI - Effects of chronic oral administration of a new beta-blocker, bopindolol, on serum lipoprotein concentrations and blood pressure of spontaneously hypertensive rats. AB - The effects of chronic oral administration of bopindolol (twice daily for 12 weeks beginning at 5 weeks of age) on serum lipoprotein concentrations, blood pressure and heart rate, were studied in spontaneously hypertensive rats. They were compared with those of two other beta-blockers. Bopindolol and propranolol (15 mg/kg) attenuated the increase in heart rate. Pindolol produced a similar, gradual change in heart rate, but only after the 6th week of treatment. Propranolol and bopindolol attenuated the development of hypertension, whereas pindolol showed no such effect. Pindolol and bopindolol produced a significant increase in high-density lipoprotein cholesterol concentration, but did not produce an increase in serum creatine phosphokinase activity. Administration of these drugs in an acute regimen at 10 weeks of age, provoked changes in blood pressure and heart rate, reflecting partial agonist activities of varying degree, in agreement with the results obtained in chronic experiments with regard to serum lipoprotein concentrations. Pindolol (5 mg/kg) provoked a larger decrease of blood pressure without decrease of heart rate, while the decrease of blood pressure after bopindolol (5 and 15 mg/kg) was associated with a decrease of heart rate. It was concluded that bopindolol is a beta-adrenergic blocking agent with a mild partial agonist activity and devoid of adverse effects on lipid metabolism. PMID- 2576893 TI - Interactions of carteolol and other beta-adrenoceptor blocking agents with serotonin receptor subtypes. AB - The importance of the anti-serotonergic activity of carteolol and other beta adrenoceptor blockers in their efficacy as anti-migraine agents has been examined in the membrane fraction of rat brain frontal cortex and pig choroid plexus, using radioligand binding methods. Carteolol and l-propranolol, which are suggested to have anti-migraine activity in man, were found to be active inhibitors of the binding of [125I]ICYP to 5-HT1B recognition sites and of [3H]-8 OH-DPAT to 5-HT1A recognition sites. Carteolol is devoid of activity at 5-HT1C and 5-HT2 recognition sites, whereas l-propranolol shows substantial affinity for these receptor subtypes. Atenolol, another beta-adrenoceptor blocker with anti migraine activity, is devoid of activity at any of the 5-HT receptor subtypes examined. The possibility that carteolol and other beta-adrenoceptor antagonists exert their pharmacological effects through central 5-HT receptor subtypes is discussed in relation to the potential mechanism of the anti-migraine activity of carteolol. PMID- 2576894 TI - [The primary and secondary pathological changes in the brain in patients with epidemic hemorrhagic fever]. AB - Pathological changes of brain in 12 patients died of epidemic hemorrhagic fever were analysed. Those cases having clinical history of hypotension and typical shock showed ischemic changes and necrosis of brain and its seguelae accompanying synchronous with infarct-like necrosis of the kidneys or pituitary gland (secondary change). One patient who died in the febrile stage showed scattered necrosis of nerve cells with neuronophagia (primary change). Immunocytochemical study on one recent case showed diffusely distributed positive virus antigen in neurons and glial cells of various kinds and even occasional positive reaction was seen in the nuclei. PMID- 2576892 TI - Role of beta 2-receptor stimulation in the peripheral vascular actions of the antihypertensive dilevalol. AB - Dilevalol (SCH 19927) is a potent, long-acting, nonselective beta-blocker with marked vasodilator actions. Unlike classical beta-blockers, dilevalol promptly lowers blood pressure and vascular resistance in animal models of hypertension. The present studies address the peripheral vascular effects of dilevalol and explore the role of beta-receptor agonism in the acute vasodilator and antihypertensive effects of the compound. In the denervated dog hindlimb preparation, dilevalol (0.1, 0.3, 1.0 and 3.0 micrograms, i.a.) significantly increased femoral blood flow by 12 +/- 6, 27 +/- 6, 84 +/- 31 and 132 +/- 41 ml/min, respectively. In contrast, celiprolol, a beta-blocker with purported vasodilator activity, caused a significant increase in flow of 31 +/- 9 ml/min at a dose of 30 micrograms i.a. Systematic pretreatment with the selective beta 2 antagonist ICI 118,551 virtually abolished dilevalol's vasodilator effect in the dog hindlimb. In conscious spontaneously hypertensive rats, 3 mg/kg i.v. dilevalol reduced blood pressure by 58 +/- 8 mmHg (P less than 0.05) and vascular resistance by 171 +/- 27 dyne.sec.cm-5/100 g (P less than 0.05) but did not change cardiac output significantly. Pretreatment of spontaneously hypertensive rats with ICI 118,551 significantly reduced both dilevalol's antihypertensive and resistance-lowering effects. Oral doses of 10 and 25 mg/kg dilevalol lowered blood pressure by 19 +/- 3 (P less than 0.05) and 37 +/- 5 mmHg (P less than 0.05) in spontaneously hypertensive rats with chronically implanted Doppler flow probes. The lower dilevalol dose reduced mesenteric vascular resistance 38 +/- 6% (P less than 0.05) while the higher dose significantly lowered vascular resistance in the hindlimb, mesenteric and renal vascular beds of spontaneously hypertensive rats by 18 +/- 8, 33 +/- 2 and 43 +/- 4%, respectively. Propranolol lowered neither blood pressure nor regional vascular resistances at the above doses in spontaneously hypertensive rats. Thus, dilevalol promotes a generalized fall in vascular resistance. Furthermore, the present studies illustrate that beta 2-receptor stimulation plays an obligatory role in both the vasodilatory and antihypertensive actions of dilevalol. PMID- 2576895 TI - [Effect of H2 blockers on the surgical indications for peptic ulcer]. AB - The effects of introduction of cimetidine therapy were studied by an analysis of all cases of peptic ulcer who came to be operated at the Hospital das Clinicas of the University of Sao Paulo in the period between 1966 and 1985. A reduction in the frequency of surgical interventions especially after 1978, was verified. Ten percent of all cases operated between 1973 and 1985 and chosen at random were studied in a more detailed way. A reduction in the number of operations for gastric and duodenal ulcers was found. There was a greater interval between diagnosis and surgery, an increased number of operations for stenosis and hemorrhagic peptic ulcers and a reduction in frequency of operations for perforated peptic ulcer. There were no significant differences as to the sex and age of patients, except in cases of perforated peptic ulcer, with a larger number of female patients. PMID- 2576896 TI - [Salicylic derivatives in the clinical treatment of inflammatory bowel disease: new perspectives]. AB - Sulfasalazine is one of the most used drugs in the clinical management of inflammatory bowel disease. Nevertheless up to 30% of the patients experiment side effects related to the drug and end up having the drug diminished or withdrawn. The new salicylic-derivate compounds emerge as a reliable alternative for these patients. The authors review the new preparations and discuss their characteristics, indications and side effects. PMID- 2576897 TI - [Soldering with laser radiation. A future technic for the dental laboratory]. PMID- 2576899 TI - Drug therapy in patients with diabetes mellitus: an audit. AB - The drug therapy prescribed for 412 diabetic patients attending an outpatient clinic over a 12 week period was recorded to try and identify potential therapeutic problems. Over 90% of the patients were prescribed at least one drug (including insulin) with oral hypoglycaemic agents prescribed for 86% of non insulin requiring diabetics. 19% of patients were prescribed more than three drugs and few patients took drug combinations. Of patients prescribed either glibenclamide or chlorpropamide, 63% were aged 65 yr or older. Despite their potential adverse clinical and biochemical effects, diuretics and beta-blockers were commonly prescribed, especially in hypertension. The prescribing of "newer" anti-hypertensive drugs, combination products in patients taking a multiple drug regimen, and the potential dangers of sulphonylureas in the elderly are three areas where alteration of prescribing habits may be of value. PMID- 2576898 TI - Modulation of arachidonic acid metabolism has limited effects on the development of type I diabetes in animal models. AB - The therapeutic potential of modulators of arachidonic acid metabolism was probed in two animal models of type I (insulin-dependent) diabetes. Sulphasalazine treatment (50 and 400 mg/kg) did not affect diabetes development in the low dose streptozotocin model in male CD-1 mice nor in diabetes prone BB/WorD rats (100 mg/kg). Administration of acetyl salicylic acid (50 mg/kg) or BW755C (60 mg/kg) caused partial suppression of hyperglycaemia in male C57BL/6 mice after low dose streptozotocin. Twice daily treatment of BB rats with acetyl salicylic acid (5 mg/kg) did not significantly alter the course of diabetes development. We conclude that modulation of arachidonic acid metabolism has limited effects on immune-mediated diabetes. PMID- 2576900 TI - An evaluation of tricalcium phosphate as a treatment for endodontic perforations. AB - In the rat, perforations of maxillary molars were created and treated with either tricalcium phosphate (Synthograft) or Cavit. At four time intervals (1 day, 1 wk, 2 wk, and 1 month), four evaluative factors (inflammation, bone resorption, cementum and dentin resorption, and epithelial proliferation) were analyzed and compared for the two materials. For the individual time periods, there were no statistically significant differences between the two materials. However, when all four time periods were combined, there was a statistically significant better result for tricalcium phosphate than for Cavit with respect to decreased inflammation (p less than 0.05). PMID- 2576901 TI - Meige's syndrome during long-term neuroleptic treatment. AB - Two patients developed difficulties in eyelid opening following long-term neuroleptic treatment of more than 6-8 years. Tardive dyskinesia and dystonia apart from the face were not found in either case. The symptoms fluctuated in their severities on a daily basis and were easily aggravated by various stimuli, e.g., stress, walking, reading and watching television. Electromyographic studies of their faces clearly indicated that the symptoms resulted from spontaneous blepharospasm and were analogous to idiopathic Meige's syndrome. Therefore, the patients' difficulties in opening their eyes were considered to be the so-called drug-induced Meige's syndrome and/or facial tardive dystonia. It must be stressed that this syndrome is extremely distressing to patients and is a severe complication accompanying a long-term neuroleptic treatment. PMID- 2576903 TI - Treatment of asthma with beta-adrenergic drugs. PMID- 2576904 TI - Salmonella meningitis complicated with subdural empyema, brain abscess and purpura fulminans: report of one case. AB - There exists high incidence of bacteremia, sepsis and meningitis in young infants with Salmonella infection. However, focal intracranial abscesses due to Salmonella infections are rare. We reported a 2-month-old male baby presenting salmonella infection with brain abscess and purpura fulminans. The patient's clinical course was fulminant. He was admitted due to fever, irritability, anemia and leukopenia. He developed cardiac arrest, shock and skin diathesis on his second hospitalization day. After resuscitation he became comatous and showed acrocyanosis and gangrenous skin over the hands, feet and left ear lobe. Both blood and cerebrospinal fluid cultures were Salmonella Group B. The patient got worse rapidly in spite of vigorous treatment. Subdural empyema, ventriculitis and later brain abscess were detected by serial brain sonograms. He died of central nervous system failure, gastrointestinal bleeding and renal failure on the eighteenth hospitalization day. PMID- 2576902 TI - [The effect of parenteral gold preparations on heart function in rheumatoid arthritis patients (based on echocardiographic data)]. AB - A total of 30 patients were treated by chrisanolum and myocrisin. The course of treatment lasted more than 2 years. The authors observed clear positive effect of parenteral preparations of gold on the contractile and pumping function of the heart in RA patients; clinical and laboratory manifestations of the disease were decreased. PMID- 2576905 TI - [Determination of unchanged clobazam in plasma by gas-liquid chromatography]. AB - A method has been developed for gas-chromatographic determination of clobazam in human plasma using a nitrogen-selective detector. The unchanged drug was extracted from the plasma at pH 9 by benzene. The method used methyl-1-clonazepam as internal standard. Calibration graphs were linear in the range of 20 to 10,000 ng/ml. The recovery of the compound was 102.29%. The sensitivity of the method was adequate for determination of the drug at toxic concentrations and at therapeutic doses. It was a simple, rapid, reproductible method for determination of clobazam and most of the commercialized benzodiazepines. The method has been tested in a few number of clinicals cases. No interferences occurred in plasma from patients treated with various drugs. PMID- 2576906 TI - [Infective complications of the central nervous system (CNS) in addicts to parenterally administered drugs]. AB - Given the high rate of infection by HIV in the APAD in our country, the description of localized infectious problems in the CNS secondary to drug addiction should always take into account opportunistic infections or tumours occurring there. The initial clinical evaluation should highlight or rule out the presence of clinical indications (specially polyadenia and oral candidiasis) which suggest a clinical condition of immunodepression. Septic embolization due to bacteremia and fungemia is common among drug-addicts, sometimes causing, although not very often in comparison with other sites, various infectious complications in the CNS (meningitis, cerebral abscess, subdural empyema or epidural abscess), "Staphylococcus aureus" being the micro-organism most frequently involved. From 1977 to 1986 the work-group for the study of infections among drug-addicts has listed 6,481 infections. Disseminated candidiasis (582 cases) and infectious endocarditis (506 cases) were the most frequent types of primary infection. Only 33 cases of infection of the CNS were observed, meningitis being the most frequent (57%). The usual empirical antibiotic treatment for meningitis is cefotaxime or cefotriaxona plus cloxacillin, and for cerebral abscess we substitute metronidazole for isoxazolic penicillin. Given the sexual habits frequently associated with APAD, neurosyphilis is suspect, since immunodepression secondary to infection by HIV causes changes in its natural behaviour. Tetanus is the most serious and uncommon infectious complication connected with drug-addiction. In our society, up to 1986 only 5 cases had been described. As for paludism, the cases detected in this country have belonged to two small outbreaks: one with four cases in Madrid with "Plasmodium vivax" and the other with three cases in Tortosa (Tarragona) with "P. falciparum". PMID- 2576907 TI - New training for new roles. AB - Assistant medical practitioners in Sri Lanka are justifiably dissatisfied with their training, which should be modified so that they are enabled to function more effectively in the country's predominantly rural communities. Furthermore, in order to motivate these health professionals to the greatest possible extent, they should be offered an attractive career structure. PMID- 2576908 TI - CD4 and the immunopathology of AIDS. PMID- 2576909 TI - Enhanced accessory cell function by alveolar macrophages from patients infected with the human immunodeficiency virus: potential role for depletion of CD4+ cells in the lung. AB - Mononuclear phagocytes, including alveolar macrophages (AM), can be infected by the human immunodeficiency virus (HIV). Acting as accessory cells (AC), AM could infect CD4 lymphocytes through cell-to-cell contact and by inducing T cell proliferation, which increases lymphocyte susceptibility to infection. Using normal allogeneic T cells as responders, AM from infected individuals demonstrated an enhanced ability to stimulate a Con A and pokeweed mitogen lymphocyte proliferation assay compared with normal AM. Exogenous IL 1 enhanced the stimulation of a mitogen response by normal AM, but not from HIV-positive individuals, suggesting increased levels of this cytokine may explain the observed enhancement. However, increased IL 1 secretion by AM from HIV-infected patients could not be demonstrated, either in a bioassay or antigenically using an ELISA for IL-1 beta. Syncytia formation was observed when AM from asymptomatic HIV-positive individuals were cultured with normal T cells, suggesting viral transmission was occurring. Finally, in individual patients the stimulation of a mitogen response was inversely correlated with the CD4/CD8 ratio and total CD4 count, suggesting that enhanced AC function and CD4 cell depletion may be related in vivo. These findings indicate that enhanced AM accessory cell function is seen in HIV-infected individuals and could be a potential mechanism for CD4 cell depletion in the lung. PMID- 2576910 TI - [Use of dystrophin c-DNA for the direct diagnosis of Duchenne muscular dystrophy in female carriers]. AB - DNA polymorphisms have been widely used as genetic markers for identification of the X chromosome that carries the mutation for Duchenne Muscular Dystrophy (DMD) in affected families, but serious limitations are associated with this approach. The complementary DNA (c-ADN) of the DMD gene has recently been isolated and shown to detect partial gene deletions in a large proportion of patients. We present the study of five DMD families in which we have shown the existence of a partial deletion in the DMD gene in the affected boys. We have evaluated the usefulness of this direct approach to diagnose DMD carriers in these families using the c-DNA derived probes. In all cases we have obtained satisfactory results. The method seems to be more reliable, more rapid and less expensive than linkage studies with DNA polymorphisms. PMID- 2576911 TI - [The use of vecuronium for intubation in general surgery]. PMID- 2576912 TI - [Analeptics and anesthesia]. PMID- 2576913 TI - PAF-acether-induced mortality in mice: protection by benzodiazepines. AB - Intraperitoneal injection to mice of platelet-activating factor (PAF) induces severe shock symptoms, leading to death. The effects of various drugs which are potential specific or non-specific PAF inhibitors were tested. Salbutamol, a beta 2-agonist, showed a partial protection, whereas the specific PAF antagonists CV 3988 or BN 52021 induced an important beneficial action against PAF-induced lethal effects. The effects of drugs related to benzodiazepines were also studied: alprazolam administered p.o. prior to PAF challenge provides almost complete protection against PAF toxicity. Thus PAF-induced death in mice represents a useful model of systemic anaphylaxis; moreover, studies of benzodiazepine-related compounds may be interesting for investigating the mechanisms of the biological actions of PAF. PMID- 2576914 TI - Reasons for seeking treatment after traumatic dental injuries. AB - The purpose of this study was to determine the reasons why parents of children seek treatment after traumatic injuries to primary teeth. The sample consisted of 114 5-month to 8-year-old children with 196 injured primary teeth. The reason for parents seeking treatment varied according to the type of injury. Parents of children with enamel fractures and enamel-dentin fractures without pulpal exposure were more concerned about esthetics. Of the patients presenting concussions, parents were more responsive to color change of the tooth and to the tooth response to the trauma, mainly abscess formation. In luxations and lateral displacements, the parents sought dental treatment because of their own reaction to the clinical situation, i.e., blood, crying. Very few were concerned with possible consequences to the primary and/or permanent teeth. In no category of injury were the parents most concerned about the consequences to the primary and/or permanent teeth. PMID- 2576915 TI - A requirement for low concentration of hepatic glutathione for induction of gammaglutamyltransferase by phenobarbitone. AB - The effect of low concentration of hepatic glutathione on the induction of GGT by phenobarbitone was investigated. Rats were treated with diethyl maleate to decrease the hepatic concentration of GGT and with cysteine to increase glutathione concentration in the liver. All animals were then treated with phenobarbitone. The study shows that the induction of GGT is promoted by low concentration of hepatic glutathione. PMID- 2576916 TI - Cardiopulmonary complications of selective beta 2 adrenergic tocolytic therapy. PMID- 2576917 TI - [Activity of gamma-glutamyltranspeptidase in clear cell carcinomas of the human kidney and renal cortex]. AB - In 30 operated patients (23 men and 7 women) we determined the activity of GGTP in the tissue of renal clear-cell carcinomas and in their renal cortex. It was found that the enzyme activity was constantly lower in the tumours than in the spared kidney however with a correlation between the enhancement of GGTP activity in the renal cortex and clear-cell carcinomas originating in the tissue of the cortex. In contrast we did not observe a relation between the degree of morphological differentiation of the neoplasms and GGTP activity. The authors discuss the problem in the light of literature data. PMID- 2576919 TI - The effect of isofloxythepine in EEG. PMID- 2576918 TI - [Calcitonin as an alternative treatment for root resorption]. AB - Inflammatory root resorption is a common finding following trauma and will cause eventual destruction of the tooth root if left untreated. This study examined the effects of intrapulpal application of calcitonin, a hormone known to inhibit osteoclastic bone resorption, on experimental inflammatory root resorption induced in monkeys. Results were histologically evaluated using a morphometric technique and revealed that calcitonin was an effective medicament for the treatment of inflammatory root resorption. It was concluded that this hormone could be a useful therapeutic adjunct in difficult cases of external root resorption. PMID- 2576920 TI - Isofloxythepin in restless oligophrenic children. PMID- 2576921 TI - Some parameters of the immune system at schizophrenia therapy with chlorpromazine and zetidoline. PMID- 2576922 TI - Controlled cross-over comparison of carbamazepine with perphenazine in schizophrenic psychoses. PMID- 2576923 TI - First experience with the application of 7-methoxytacrine to psychiatric patients. PMID- 2576924 TI - Dose-dependent effects of vasoactive intestinal polypeptide on somatostatin release from hypothalamic fragments in vitro. AB - 1. Vasoactive intestinal polypeptide (VIP) is present in high concentrations in the hypothalamus and appears to be involved in the modulation of growth hormone (GH) secretion. The effects of VIP on hypothalamic somatostatin (SMS) release are, however, controversial. 2. To further elucidate the mechanism of action of this peptide on GH secretion we studied the effects of VIP on SMS secretion from incubated rat hypothalamic fragments in vitro. 3. At 10(-6) M, VIP induced a significant increase in basal SMS release (P less than 0.01), whereas at 10(-10) M it had an inhibitory effect. 4. We suggest that the increase in GH after in vivo administration of VIP may be modulated, at least in part, by a direct effect of this peptide on SMS neurons, while the stimulatory effect of high doses of VIP on SMS release may represent a pharmacological interaction of this peptide with growth hormone releasing hormone, peptide histidine isoleucine, or glucagon receptors. PMID- 2576925 TI - [Role of the pyloric antrum plexus in gastric peristalsis]. PMID- 2576926 TI - [Anticholinesterase effect of histamine H2 receptor blockaders on gastric motility]. PMID- 2576927 TI - [Activity and molecular form of intestinal gamma-glutamyltransferase (GGT) EC 2.3.2.2. in celiac disease]. AB - It has been shown that GGT activity in the duodenal biopsy homogenates of the children with coeliac disease (n-10) in remission (1 to 3 years of gluten-free diet) is lower than in those with other gastrointestinal tract diseases (n-6). In children with coeliac disease after gluten challenge (1 g of gluten) kg BW for 3 to 6 months) the GGT activity decreased fourfold (n-10). After a few months of gluten challenge there was in coeliac children (n-5) a marked predominance of GGT without sialic acid (the asialic GGT). Similarly there was a prevalence of this form (n-5) in the gut tissue of 3 month old human fetus. In the homogenates of the duodenal bioptates of the children with other gastrointestinal tract diseases (n-6) there was a predominance of the sialic form of the GGT. In the gut tissue of children older than 3 years (n-6) and adults who died of reasons other than gastrointestinal a marked predominance of the sialic form of GGT was found. It has been suggested that presence of asialic form of GGT in coeliac disease is connected with the lectin-like activity of gluten. The process of sialization or desialization takes place within or outside enterocytes. It changes the gut permeability and causes a secondary reaction to the penetrating allergens. PMID- 2576928 TI - HIV-1-stimulated expression of CD11/CD18 integrins and ICAM-1: a possible mechanism for extravascular dissemination of HIV-1-infected cells. AB - To identify mechanisms which might facilitate emigration of HIV-1-infected cells from the circulation, we studied the effect of HIV-1 infection on T lymphocyte and monocytoid cell expression of molecules involved in adherence and translocation of leukocytes across endothelial cell barriers. CD11a, CD18, and ICAM-1 were demonstrated on up to 80% of HIV-1-infected H9 T cells by flow cytometry; these molecules were not evident on uninfected H9. CD18 mRNA was detected in HIV-infected, but not in uninfected H9 T cells. Cell surface expression of CD11a and CD18, but not ICAM-1, was increased on HIV-infected, as compared to uninfected U937 and THP1 monocytoid cells. Increased cell surface expression of the leukocyte integrins was associated with a significantly increased tendency of HIV-infected monocytoid cells to adhere to human umbilical vein endothelial cell monolayers or aggregate homotypically. Preincubating the monocytoid cells with anti-CD18 or anti-CD11a or preincubating endothelial cells with anti-ICAM-1 suppressed these cell to cell interactions. These studies suggest that HIV-1 infection stimulates cell surface expression of molecules involved in leukocyte adherence and transendothelial migration in vitro. Similar mechanisms may influence leukocyte trafficking, in vivo, and may play a role in the localization of HIV-1 infected cells in the central nervous system and other tissues. PMID- 2576929 TI - The growth hormone receptor gene in the African pygmy. AB - Multiple studies indicate that the pygmy responds poorly to GH. A GH-binding protein, which is a fragment of the GHR is markedly diminished in pygmy serum, suggesting a defect in the GHR. Full analysis of the molecular nature and function of the GHR gene is incomplete, but with one enzyme BstNI restriction fragment length, polymorphism was noted in pygmies located in an intron. This was an uncommon finding in other non-pygmy populations. The alteration noted may be in linkage disequilibrium with an effective mutation responsible for changes in the GHR of the pygmy. This is most likely in the regulatory regions of either the 3' or 5' extensions. PMID- 2576930 TI - Cardiovascular responses of rats to electrical stimulation of the fastigial nucleus and local microinjection of amino acids. AB - The cardiovascular response to electrical stimulation of the fastigial nucleus (FN) and microinjection of L-glutamate, kainic acid, glycine and GABA into the FN of anesthetized rats were studied. Electrical stimulation of FN produced pressor or depressor responses with a decrease or no change in heart rate depending upon the intensity or site of the stimulation. Microinjection of L-glutamate or kainic acid into the FN elicited pressor or depressor response with bradycardia, while that of glycine or GABA did not affect blood pressure or heart rate. L-glutamate or kainic acid microinjected into the FN did not affect epinephrine-induced pressor response, but attenuated the bradycardic response. These results indicate that L-glutamate in the FN may play a role in modulation of the cardiovascular regulation. PMID- 2576931 TI - Induction of rifampicin metabolism during treatment of tuberculous patients with daily and fully intermittent regimens containing the drug. AB - Self-induction of rifampicin metabolism during daily and intermittent chemotherapy was studied by monitoring the changes in the serum half-life of the drug over a 4-week period in patients with pulmonary tuberculosis. Rifampicin 450 mg was administered to 8 patients who received treatment daily, 7 on thrice weekly and 7 others on twice-weekly treatment. Serum half-life was computed from concentrations of the drug determined at 3, 4 1/2 and 6 hours after drug administration, on admission and at 1, 2 and 4 weeks after start of treatment. In the daily series, the mean serum half-life decreased from 4.9 hours on admission to 3.6 hours at 1 week (P = 0.02), and treatment beyond this had no further effect. In the thrice-weekly series, maximal induction was observed at the 2nd week, the mean values on admission and at 2 weeks being 5.8 and 3.7 hours, respectively (P less than 0.01). In the twice-weekly series, maximal induction was observed only at the 4th week, the mean values on admission and at 4 weeks being 4.9 and 3.7 hours, respectively (P less than 0.01). Serum activity of gamma glutamyl transferase was not found to be a suitable in vivo marker to monitor induction of the hepatic microsomal enzymes as no significant changes were observed in the activity of this enzyme in any of the 3 series during the 4-week period. PMID- 2576932 TI - Department of Health and Human Services, Public Health Service, National Institutes of Health. Recombinant DNA Advisory Committee. Minutes of meeting, October 6, 1989. PMID- 2576933 TI - Gamma interferon induces different keratinocyte cellular patterns of expression of HLA-DR and DQ and intercellular adhesion molecule-I (ICAM-I) antigens. AB - With indirect immunofluorescence techniques we demonstrated that recombinant gamma-interferon induced the expression of the class II antigens HLA-DR and HLA DQ as well as intercellular adhesion molecule-I (ICAM-I) on normal, cultured human keratinocytes grown in low-calcium, serum-free medium. Each antigen displayed a distinctive cellular staining pattern. HLA-DR was strongly localized to perinuclear zones with intense cell surface expression; HLA-DQ displayed a perinuclear accentuation, but with minimal cell surface staining, and ICAM-I was strongly expressed in a diffuse cytoplasmic pattern with intense cell surface expression. Keratinocytes grown in medium supplemented with 10% fetal calf serum underwent differentiation, with a diminished expression of all three antigens as compared to those grown in low-calcium, serum-free medium. These results confirm that gamma interferon can differentially regulate HLA-DR and HLA-DQ expression; that there are probably different biochemical metabolic pathways by which these three molecules are expressed on keratinocytes, and that the expression is also a function of the degree of keratinocyte differentiation. The strong cell surface expression of ICAM-I is suggested to be of major importance as the recognition molecule, by which T cells bind to gamma interferon exposed keratinocytes, and suggests an integral role for this molecule in epidermal lymphocyte trafficking. PMID- 2576934 TI - Vibratory angioedema: lesion induction, clinical features, laboratory and ultrastructural findings and response to therapy. AB - We report the investigation and treatment of a 28-year-old woman with the rare condition of non-familial vibratory angiodema. Lesions were reproduced using a vibrator set at pre-determined frequencies and amplitudes, applied for a fixed time period. There was no indication of the production of tolerance in the patient with repeated vibration, but terfenadine produced a good therapeutic response. There was no evidence of mast cell degranulation at the ultrastructural level. The patient also had mild delayed pressure urticaria and dermographism, thus demonstrating the clustering frequently found in the physical urticarias. PMID- 2576935 TI - Heparin-induced increase in plasma and serum gamma-glutamyl transpeptidase activity. AB - gamma-Glutamyl transpeptidase (GGT) activity may be a sensitive index of hepatobiliary dysfunction. GGT activity, however, has been shown to be affected by several factors in different clinical situations. The present study was designed to determine the effect of heparin on serum and plasma GGT activity. Blood samples were collected from 15 normal male Wistar rats weighing 200-250 g for the determination of GGT activity in plasma prepared with heparin (group P(H), N = 10), in serum (group S, N = 15) and in serum with heparin added (group S + H, N = 10). GGT activity was 45.1 +/- 9.5 U/l (mean +/- SD) for serum compared with 161.2 +/- 46.1 U/l for serum plus heparin and 93.3 +/- 30.9 U/l for plasma prepared with heparin. The mean for each group was significantly different from the means for the other groups. These data demonstrate that GGT activity measurements should be made on serum in the absence of heparin, which produces elevated results. PMID- 2576937 TI - Early detection of hereditary medullary thyroid cancer with polymorphic DNA probes. Groupe d'Etude des Tumeurs a Calcitonine. AB - We have performed linkage analysis on 32 families with hereditary medullary thyroid cancer (MTC) with seven polymorphic DNA probes situated near the centromere of chromosome 10. Nineteen of these families were affected with multiple endocrine neoplasia type 2A (MEN 2A), and the remainder had MTC without pheochromocytoma. There were no instances of recombination between the MEN 2A susceptibility gene and the IRBP.H4 marker. Two other probes, TB14.34 and MCK2, are also tightly linked (theta = 0.00 and theta = 0.02, respectively). Because TB14.34 and IRBP.H4/MCK2 are situated on opposite sides of the MEN 2A gene, screening with flanking DNA markers is now feasible. PMID- 2576936 TI - Closing in on the MEN2A locus. AB - The mapping of the locus for multiple endocrine neoplasia type 2A (MEN 2A) to chromosome 10 using linkage is briefly reviewed including a discussion of linkage strategy and reference to some of the exclusions before the assignment. The subsequent development of the map of the centromeric region of the chromosome and the linking of what appear to be the four closest flanking markers and the centromeric alphoid sequence to the disease locus are reviewed. To date no recombination has been observed between the centromeric marker and the MEN2A locus among, at least, 26 informative meioses, 11 of which are phase known. While no obligate recombination has been observed between the markers FNRB, D10S34, and RBP3 and the MEN2A locus in males, it has been observed in females and is as much as 10% for the marker RBP3. The sex difference in recombination frequency is significant. The four polymorphic flanking markers, FNRB, D10S34, RBP3, and D10S5, along with the centromeric marker D10Z1 will prove to be useful for management of the families with the disease. It will be possible in most families to give a very high (or low) probability for "at risk" members of the families and in some cases the DNA results will be virtually diagnostic. PMID- 2576938 TI - Hereditary medullary thyroid carcinoma: genetic annalysis of three related syndromes. Groupe d'Etude des Tumeurs a Calcitonine. AB - Hereditary medullary thyroid carcinoma (MTC) appears in three forms: 1) in association with pheochromocytomas and parathyroid hyperplasia (multiple endocrine neoplasia type 2A [MEN 2A]); 2) with pheochromocytomas, neuromas of the mucous membranes, and a marfanoid appearance (MEN 2B); and 3) without pheochromocytoma. Despite these differences in presentation, age of onset, and clinical severity, limited genetic studies suggest that the three MTC variants may be due to inherited mutations at the same gene locus. We present further data in support of the hypothesis that allelic variation may underlie the diversity of these endocrine neoplasia syndromes. PMID- 2576939 TI - Allele loss on chromosome 10 and point mutation of ras oncogenes are infrequent in tumors of MEN 2A. AB - The multiple endocrine neoplasia type 2A (MEN 2A) gene has been mapped to the centromeric region of chromosome 10 by linkage analysis. We examined 36 medullary thyroid carcinomas (MTCs) (16 hereditary and 20 sporadic) and ten pheochromocytomas (eight hereditary and two sporadic) to detect loss of alleles on chromosome 10 using seven polymorphic DNA markers mapped to this chromosome. Of 20 informative cases, only one (5%) sporadic MTC showed loss of heterozygosity at the locus RBP3. Allele loss at the RBP3 locus was not found in pheochromocytomas from six heterozygotes. All tumors retained constitutional heterozygosity at six other loci on chromosome 10 (D10S17, D10S34, D10S24 on the short arm, D10S15 in the pericentromeric region, D10S20, and D10S4 on the long arm). Our findings suggest that the second hit for tumorigenesis in MEN 2A may not be loss of function of the normal allele at the homologous locus on the other copy of chromosome 10. Mutated ras oncogene was found only in one of 18 MTCs at the codon 61 of H-ras. PMID- 2576941 TI - Screening for medullary thyroid cancer in France: a national effort. French Medullary Study Group (GETC). AB - Screening for medullary thyroid cancer (MTC) in France is based on a protocol that has been widely distributed nationally. A network of coordinators utilizing a common questionnaire provides for an effective national screening program. Calcitonin stimulation procedures are systematically used for all first-degree relatives of MTC patients. Pathological studies utilize special immunopathologic techniques. Genealogic information is obtained on all index cases, and blood specimens are collected for establishing permanent cell lines. The data collected are used not only to establish the diagnosis of the hereditary or sporadic form of the disease but also to expand the screening as appropriate. This common protocol has benefited patients and their families by improving early detection of cases, increasing the number of families available for follow-up, and improving the prognosis of this cancer. Studies on these families have contributed significantly to the localization of the multiple endocrine neoplasia type 2 gene. PMID- 2576940 TI - Genetic mechanisms of neoplasia in MEN 2. AB - Several possible mechanisms for the initiation and progression of tumors in multiple endocrine neoplasia type 2 (MEN 2) merit consideration. Localization of MEN2A to the pericentromeric area of chromosome 10 indicates the site of the initial mutagenic event but does not explain the tissue specificity observed. The consistency of tissue involvement within families, despite the variability between families, suggests that the tumors result from separate but contiguous tissue-specific genes arranged in a particular linear order. Linkage studies in MEN 2A and 2B families are compatible with this contiguous gene theory. Data suggest that Knudson's two-mutational-event theory is applicable in MEN 2, with cellular hyperplasia resulting from the initial heritable mutation. The second event could be a homozygous allelic mutation, but the lack of consistent loss of heterozygosity of chromosome 10 markers in tumors suggests other mechanisms. Observations in MEN 2 may be explained by the heritable chromosome 10 mutation causing hyperplasia, with the hyperplastic cells being converted to cancer cells by second mutations at any of many possible sites. Tumor progression probably involves subsequent events at other loci. These hypotheses may have important clinical implications. PMID- 2576942 TI - The importance of screening for medullary thyroid carcinoma in families of patients with MEN 2. AB - Family screening for medullary thyroid cancer (MTC) is important for detecting members of multiple endocrine neoplasia type 2 (MEN 2) families who may be gene carriers but show no clinical evidence of the disease. Most members of our MEN 2 families are screened yearly by measuring basal and pentagastrin-stimulated calcitonin (CT) levels. A 15-year-old first-degree relative of an affected member of the D-kindred showed a normal basal and an elevated stimulated CT level. Clinical examination, ultrasonography, and scintigraphy were normal. Thyroidectomy and bilateral neck dissection revealed a multicentric MTC with no lymph node involvement. In the O-kindred we detected elevated basal and/or stimulated CT levels in three asymptomatic first-degree relatives. At surgery we found a small multicentric MTC in one family member, C-cell hyperplasia in another member, and bilateral lymph node metastases in one member who had been previously thyroidectomized. Basal and stimulated CT estimations in MEN 2 family members provide an effective method for detecting MTC in early, treatable stages. PMID- 2576944 TI - MEN 2A: update on the Northern Ireland and Australian family. AB - The Northern Ireland/Australian family with multiple endocrine neoplasia type 2A (MEN 2A) originally described in 1987 is presented with a revised and enlarged pedigree. Four members of the first generation studied have died. A seventh member of the second generation studied has developed medullary thyroid carcinoma and has progressed to surgery. None of the third generation members studied has shown any conclusive abnormality in metabolic screening tests. Each member of the third and fourth generations has had genetic counseling and (if appropriate) DNA analysis with gene probes close to the MEN 2A gene locus on chromosome 10. All members of this highly penetrant family have remained asymptomatic for their disease. PMID- 2576943 TI - Results of a screening program for multiple endocrine neoplasia type 2A: a clinical study of a Japanese family. AB - A Japanese family of 87 members in five generations with multiple endocrine neoplasia type 2A (MEN 2A) is described regarding the utility of screening tests for early detection of medullary thyroid carcinoma and the potential for DNA diagnosis of MEN 2A gene carriers. The screening programs for family members in this series include measurements of plasma calcitonin concentrations after intravenous injection of pentagastrin (0.5 micrograms/kg/5 sec) and 24-hour urinary excretion of catecholamines. While 18 MEN 2A patients had been previously diagnosed, these screening programs revealed five additional patients with MEN 2A (aged 16, 19, 35, 37, and 57). Prediction of MEN 2A gene carriers by DNA analysis has been attempted but is not yet possible in this family. PMID- 2576945 TI - Screening for pheochromocytoma in the MEN 2 syndrome. AB - Twenty-two patients with the multiple endocrine neoplasia type 2 (MEN 2) syndrome were screened for pheochromocytoma since it is a major cause of morbidity in MEN 2 families. Clinical symptoms, biochemical parameters, ultrasound, computed tomography or magnetic resonance imaging, and meta-iodo-benzylguanidine (MIBG) scintigraphy were evaluated for detection of adrenal tumors. Clinical symptoms and plasma or urine catecholamines appeared to be nonspecific, whereas MIBG scintigraphy was highly specific and the most sensitive parameter. Patients older than age 30 should be scintigraphically screened at least once despite the radiation exposure. Demonstration of only slight uptake is not an indication for surgery but rather for careful follow-up. PMID- 2576946 TI - Diagnosis, management, and pathogenetic studies in medullary thyroid carcinoma syndrome. AB - A retrospective study of 224 patients with medullary thyroid carcinoma (MTC) diagnosed between 1963 and 1988 was performed to 1) establish the diagnosis of MTC in early childhood, 2) establish the role of prophylactic regional lymphadenectomy in patients with MTC, 3) study the effect of chemotherapy on MTC patients with metastatic disease, 4) study the effect of somatostatin analog 201 995 (Sandoz Pharmaceuticals) on the frequency of diarrhea in MTC, and 5) locate the common region(s) of gene deletion on chromosome 1 and examine the loss of heterozygosity on chromosome 10 in tumors. Our data indicated that a progressive rise of serum calcitonin in early childhood (rather than the expected fall with age seen in normal subjects) is diagnostic of MTC. No differences in clinical course of prognosis were observed between patients with MTC localized to the thyroid who had prophylactic neck node dissection and those who did not. Conventional chemotherapy had no significant benefit in the treatment of patients with metastatic disease. The somatostatin analog was found to be an effective drug in the treatment of diarrhea associated with MTC. Allelic losses were frequently found in MTCs and pheochromocytomas, and the loss of DNA sequences in these tumors appeared to involve the distal third of the short arm of chromosome 1, with a common breakpoint at 1p32. PMID- 2576947 TI - Postoperative pentagastrin-stimulated serum calcitonin concentrations in patients with medullary thyroid carcinoma: reoperations in patients with concentrations bordering the detection limit. AB - The case reports on two patients with medullary thyroid carcinoma show that even postoperatively stimulated serum calcitonin (CT) concentrations near the detection limit (using a polyclonal antibody against synthetic CT) can demonstrate persistent disease. Stimulated CT concentrations can be lowered to nondetectable levels by a second and third operation if a meticulous technique is used for dissection of the lymph compartments. The patient can then be assumed to be cured. Diagnostic accuracy at very low CT concentrations can be improved by selective venous catheterization with blood sampling for CT after stimulation. PMID- 2576948 TI - Comparison of sporadic and hereditary forms of medullary thyroid carcinoma. AB - Between 1960 and 1988, 185 patients with medullary thyroid carcinoma (MTC) were followed at the Institut Gustave Roussy in France. The screening of the family members by calcitonin measurement (basal or after pentagastrin stimulation) has led to the characterization of 38 sporadic cases and 44 hereditary cases. Among the hereditary cases are seven families with MTC only and two families with multiple endocrine neoplasia type 2A (MEN 2A). MTC only cases and MEN 2B cases are present as apparently sporadic forms. Hereditary cases consisted of 26 females and 18 males; the male:female ratio was 21:17 in sporadic cases. Ten of the sporadic patients were deceased (mean age 46 years) compared to three of the hereditary cases (mean age 59 years). The age at diagnosis was 44 years for the sporadic patients and 35 years for the hereditary MTC only patients with clinical manifestations. Histologic data from the sporadic and hereditary patients showed that the tumor is mostly unilateral without C-cell hyperplasia in sporadic cases and bilateral with C-cell hyperplasia in hereditary cases. The location of tumors was quite variable among the sporadic cases and mostly localized to the middle part of the thyroid lobes in the hereditary cases. Our data suggest that the age at diagnosis is later in sporadic forms of MTC and that the age at diagnosis is later in the hereditary forms of MTC only compared to those with MEN 2A. PMID- 2576949 TI - Cutaneous lichen amyloidosis associated with multiple endocrine neoplasia type 2A. AB - We have previously described a kindred with hereditary medullary thyroid carcinoma and pheochromocytoma (multiple endocrine neoplasia type 2A [MEN 2A]) with localized pruritic cutaneous manifestations present only in affected members. Although the initial skin biopsies reported did not show amyloidosis, subsequent skin biopsy results reported here have demonstrated amyloid which stained for keratin but not for calcitonin and established that this family represents an association of a rare autosomal dominant form of lichen amyloidosis with MEN 2A. PMID- 2576950 TI - Familial cutaneous lichen amyloidosis in association with multiple endocrine neoplasia type 2A: a new variant. AB - Multiple endocrine neoplasia type 2A (MEN 2A) is a rare hereditary disease transmitted in families as an autosomal dominant trait. We have identified a family in which the expression of a rare autosomal dominant form of cutaneous lichen amyloidosis appears to cosegregate with MEN 2A. In this family the skin lesion presented as multiple infiltrated papules overlying well demarcated plaques over the scapular area (right or left). Immunohistochemical studies demonstrated amyloid which stained for keratin but not calcitonin. A total of 19 members were screened. Three members of the family have the characteristic skin lesion and MEN 2A; two additional members have MEN 2A but have not manifested observable skin changes of lichen amyloidosis. Another unrelated Italian family with a similar type of pruritic skin rash and MEN 2A has been reported recently. Although the initial skin biopsies were negative for amyloidosis, subsequent biopsy established the association of MEN 2A with amyloidosis in this family also. When these kindreds are combined, several conclusions can be drawn. First, the syndrome of cutaneous amyloidosis and MEN 2A appears to be a clearly defined autosomal dominant hereditary syndrome. Whether this syndrome can be linked to chromosome 10 is not yet known. Second, the dermal amyloid appears to be caused by deposition of keratin-like peptides rather than calcitonin-like peptides. Third, we believe that patients with the hereditary form of cutaneous amyloid should be screened for medullary thyroid carcinoma to determine the true frequency of this syndrome. PMID- 2576951 TI - Use of somatostatin analog SMS 201-995 in medullary thyroid carcinoma. AB - We have studied seven subjects with medullary thyroid carcinoma. Each had elevated basal serum calcitonin (CT) levels following total thyroidectomy. After subcutaneous administration of 100 micrograms of SMS 201-995, blood samples were collected at 60-minute intervals for six hours. Two patients showed a marked decrease of CT levels (patient A: baseline 565 pg/mL, nadir 150 pg/mL; patient B: baseline 1,632 pg/mL, nadir 416 pg/mL). The other five patients showed no significant change in comparison with saline infusion. Two patients were treated with SMS 201-995 (300 micrograms/day) for 90 days. One of these patients responded to the acute SMS 201-995 test and had CT levels persistently 50% lower than pretreatment values during this 90-day period. The other patient, whose CT levels did not decrease during the acute test, had persistently high values during this 90-day period but had relief of watery diarrhea even after the therapeutic trial was discontinued. PMID- 2576952 TI - Adrenal cortex transplantation after bilateral total adrenalectomy in the rat. AB - An experimental animal model with adrenal cortex transplantation was developed to study adrenal cortex replacement therapy in patients with multiple endocrine neoplasia type 2 who have had bilateral adrenalectomy for pheochromocytomas. Adrenal cortex of syngenetic rats was isolated from the medulla by collagenase digestion and a defined sedimentation. The cell suspension of the cortical cells was implanted under the kidney capsule of untreated syngenetic rats. After two weeks the recipients were bilaterally adrenalectomized. Serum corticosterone levels were measured as an estimate of function of the grafts. All recipients were healthy throughout the observation period, whereas all adrenalectomized controls died within 18 days. Vital cortex cells could be demonstrated in the explanted grafts by immunohistochemistry. Corticosterone levels of transplanted animals were nearly normal (9.5 ng/100 mL +/- 0.4) compared to the controls (0.20 ng/mL +/- 0.06). This animal model of adrenal cortex transplantation allows the separation of medullary from cortical cells. After transplantation, these cortical cells survived for eight weeks and were able to replace the adrenal cortex function. PMID- 2576953 TI - Surgical treatment of medullary thyroid carcinoma in a thirteen-year-old girl with MEN 2B. AB - Patients with palpable medullary thyroid carcinoma (MTC) have lymph node metastases in 90% of cases. In most series such patients continue to have elevated serum calcitonin (CT) levels after surgery indicating residual tumor tissue. We attempted a microdissection technique for the treatment of MTC. "Micro" refers not to a small incision or a limited exploration but to a more safe operation associated with good lighting and magnification and minimal bleeding. This technique was used in a 13-year-old girl with multiple endocrine neoplasia type 2B (MEN 2B). The prognosis for MTC in MEN 2B is worse than for sporadic MTC and the MTC of MEN 2A. Every possible effort should be made to remove all tumor tissue in MEN 2B patients with MTC. In this case the pathologist found bilateral MTC and metastases in eight of 129 lymph nodes removed. The preoperative stimulated CT levels, which were markedly elevated, decreased to near normal postoperatively. PMID- 2576954 TI - Quality of life after bilateral adrenalectomy in MEN 2. AB - Pheochromocytoma is a major cause of morbidity and mortality in the multiple endocrine neoplasia type 2 (MEN 2) syndrome. For the physician, surgical treatment seems well justified even though bilateral adrenalectomy will induce iatrogenically complete loss of adrenocortical function. For the patient this treatment may be a cause of medical problems as well as worry. We have evaluated quality of life after bilateral adrenalectomy in 27 MEN 2 patients through a combined oral and written approach. Mortality was low (one of 27), as was serious morbidity. Most patients had adapted well to the postadrenalectomy state. However, fatigue, worry, and noncompliance with daily medication often caused problems. PMID- 2576955 TI - Living with a hereditary form of cancer: experiences and needs of MEN 2 patients and their families. AB - Unlike the purely medical research done in multiple endocrine neoplasia type 2 (MEN 2) families, little work has been done on the psychosocial aspects of the disease. To assess the severely stressful influences and the consequences of that stress on the family network, a small-scale survey was carried out during a national meeting. The goal of the study was to obtain more information about the experiences and needs of MEN 2 patients and their relatives. Of the 59 respondents, 85% were satisfied with the medical information provided, 81% were satisfied with the medical knowledge of the specialist, but only 12% were satisfied with the medical knowledge of the general practitioner regarding MEN 2. Furthermore, 63% of the parents had difficulties in talking about the disease with their children. The need expressed for contact with fellow sufferers and their families is expected to lead to the establishment of an interest group for MEN 2 families. PMID- 2576956 TI - Experience in imaging medullary thyroid carcinoma using 99mTc (V) dimercaptosuccinic acid (DMSA). AB - 99mTc (V) dimercaptosuccinic acid (DMSA) is a new tumor imaging agent that has been successfully used to image patients with medullary thyroid carcinoma (MTC). Since 1986, studies have been performed in 32 patients with histologically proven MTC at Guy's Hospital, London, England. Five patients with primary tumor were studied prior to surgery, four patients were studied after successful removal of the primary tumor, and 26 patients with biochemical evidence of recurrence were studied. Eight patients were studied serially to assess progression of disease, and four patients were studied before and after surgery. Twenty-one of the 26 patients with disease had positive scans with four false-negative scans and three true negative scans. One patient had a false-positive scan (sensitivity 80%, specificity 75%). Two of the false-negative scans were obtained in patients with moderate but stable elevations of calcitonin but no other evidence of recurrence. One false-negative scan was obtained in a patient who was discovered on screening to have an abnormal pentagastrin response, and a small 1 cm tumor was subsequently removed. Uptake in local neck recurrence was frequently intense, but uptake at sites of bone metastases was less marked. 99mTc (V) DMSA is an inexpensive radiopharmaceutical which produces good quality images and has been shown to have an acceptable sensitivity and specificity in the follow-up of patients with MTC and thereby contributes significantly to the management of these patients. PMID- 2576957 TI - Contribution of different scintigraphic techniques to the management of medullary thyroid carcinoma. AB - We compared three different scintigraphic techniques for the localization of neck recurrences and metastases in seven patients with medullary thyroid carcinoma one month to eight years after the first surgical intervention. Three successive scintigraphic studies were performed in five patients (6 x 3 studies) within two weeks using 201Tl chloride, 111In-labeled F(ab')2 fragments of the anti carcinoembryonic antigen (anti-CEA) monoclonal antibody (MoAb) BW 431/31, and 131I meta-iodo-benzylguanidine (MIBG). Additionally, 11 studies were performed with the 111In-labeled MoAb fragment BW 431/31 (seven studies) or the 99mTc labeled intact anti-CEA MoAb BW 431/26 (four studies). The gold standards for classifying scintigraphic results were biopsy, histology, surgery, and cytology. Six regions were classified as positive or negative in each study: thyroid region, four quadrants (lymph node regions) around the thyroid, and the region of the upper mediastinum. Of 36 sites, 201Tl was true positive (TP) in seven sites, false-positive (FP) in one site, true negative (TN) in 22 sites, and false negative (FN) in six sites, resulting in a sensitivity of 54% and a specificity of 96%. 131I MIBG was TP in four sites, FP in none of the sites, TN in 23 sites, and FN in nine sites, with a sensitivity of 31% and a specificity of 100%. Immunoscintigraphy (102 sites overall) was TP in 16 sites, FP in five sites, TN in 77 sites, and FN in four sites, resulting in a sensitivity of 80% and a specificity of 94%. Immunoscintigraphy with 111In/99mTc anti-CEA F(ab')2 fragment/intact antibody is superior to scintigraphy with 201Tl and 131I MIBG. PMID- 2576958 TI - The role of radiopharmaceuticals MIBG and (V) DMSA in the diagnosis of medullary thyroid carcinoma. AB - The diagnostic value of 123/131I meta-iodo-benzylguanidine (MIBG) and 99mTc (V) dimercaptosuccinic acid (DMSA) was investigated in 12 patients with proven medullary thyroid carcinoma (MTC). Scintigraphic imaging with DMSA was negative in nine of 12 patients. Scintigraphy with MIBG was positive in only one case. In proven primary or recurrent disease, DMSA sensitivity was 50% and MIBG sensitivity was 25%. Such sensitivities become much lower in subjects with high calcitonin (CT) levels who have had negative surgical explorations: DMSA 17% and MIBG 0%. DMSA detected tumor in 25% of the patients and MIBG in only 8%. The positivity of these scintigraphies appears to be unrelated to carcinoembryonic antigen and CT plasma levels. Such data suggest that scintigraphies with MIBG and DMSA are only modestly useful in the diagnosis of MTC. PMID- 2576959 TI - Diagnostic and therapeutic potential of new radiopharmaceutical agents in medullary thyroid carcinoma. AB - Recently developed radiopharmaceuticals have been proposed for imaging medullary thyroid carcinoma (MTC) with some having therapeutic potential. This study compares the imaging results obtained with radioiodinated meta-iodo benzylguanidine (MIBG), 99mTc (V) DMSA, and 131I F(ab')2 anti-carcinoembryonic antigen (anti-CEA) in a group of MTC patients. In 23 patients 131I MIBG imaging showed a high specificity (no false-positive results) but a less satisfactory sensitivity (50%). In 12 patients 99mTc (V) DMSA revealed a better sensitivity (77%) but a lower specificity (three false-positive results). Positive results were obtained in two of three patients studied with 131I F(ab')2 anti-CEA. These data suggest that the highly sensitive 99mTc (V) DMSA should be considered as a first choice procedure followed by the highly specific radioiodinated MIBG to confirm the initial results. Since radioiodinated MIBG imaging may have therapeutic usefulness, 131I MIBG was evaluated in an integrated treatment protocol in four cases of proven MTC. The preliminary results obtained were encouraging. PMID- 2576960 TI - DNA cytophotometric findings in pheochromocytoma. AB - Fifty adrenalectomy specimens containing normal (n = 3), hyperplastic (n = 4), or neoplastic (n = 43) medullary tissue were subjected to quantitative measurements of DNA content. Of the 43 pheochromocytomas, 16 were neoplasms inherited in the setting of multiple endocrine neoplasia type 2A. Five of 27 sporadic pheochromocytomas followed a malignant clinical course. Follow-up data were available in 25 patients. In normal medulla and adrenomedullary hyperplasia either diploid or euploid DNA distributions were found. In contrast, 87% (33 of 38) of the benign and all five malignant pheochromocytomas exhibited nondiploid or aneuploid DNA histograms. No differences in DNA content existed between sporadic and hereditary tumors. In contrast to earlier reports, in this study DNA cytophotometry was not suitable to discriminate benign from malignant adrenomedullary tumors. In addition, DNA measurements appeared not to be a useful tool to assess the prognosis of an individual malignant pheochromocytoma. PMID- 2576962 TI - The Third International Workshop on Multiple Endocrine Neoplasia Type 2 Syndromes. Heidelberg, West Germany, September 28-30, 1989. Proceedings. PMID- 2576961 TI - A novel parathyroid hormone-related gene product. AB - A parathyroid hormone-related protein (PTHrP) has been invoked as being responsible for the humoral hypercalcemia of malignancy. Eight of the first 13 amino acids of PTHrP are identical with those in PTH, but there is no other significant homology. The PTHrP gene is located on chromosome 12, whereas that for PTH is on chromosome 11, and the two genes are probably related by a duplication process. Antisera against PTHrP(1-34), which cross-react poorly or not at all with PTH, and antisera against other parts of PTHrP not homologous to PTH were used in immunocytochemistry using a peroxidase-antiperoxidase method, to identify PTHrP in the cytoplasm of cells in a series of unselected parathyroid adenomata. The study was based on our evidence that PTHrP is produced by fetal parathyroid and may be the predominant calcium-regulating hormone in the mammalian fetus. Glands from five patients with parathyroid hyperplasia secondary to chronic renal failure also stained positively for PTHrP. No evidence was obtained for PTHrP in sections from five patients with primary parathyroid chief cell hyperplasia or in a small group of patients with the multiple endocrine neoplasia type 1 or type 2 syndromes. PMID- 2576963 TI - [Clinical and histological evaluation of a new filling material: natural coral]. AB - A clinical and histological study was performed to evaluate the effects of natural coral micro-granules in the treatment of infrabony defects. 12 defects in 11 patients were selected for treatment. The therapy was assessed using standardized radiographs, pocket probings and gingival margin levels 12 months after treatment. The mean initial pocket depth was 9.6 +/- 1.5 mm and at the bony defect 6.08 +/- 2.53 mm. Results showed a gain in attachment of 3 +/- 1.5 mm and a mean reduction in pocket depth of 3.9 +/- 2 mm. Two biopsies taken at 8 and 18 months post-operatively show different stages of bone formation around the coral particles. PMID- 2576964 TI - Course of psychosis in Algeria and in France: about 342 cases observed from 1975 to 1985. AB - The aim of this study was to compare the evolution of psychotic patients in Algeria and in France. In 1975, 105 patients were selected in Algeria and 237 in France. Ten years later, in 1985, all these patients were interviewed. In 1985, we investigated for each subject the evolution of the following parameters: sex, age, DSM-III axis 1 and 5, marital status, social welfare work, and treatment variables. Our results indicate that the improvement of the psychosocial adaptation (DSM-III axis 5) is slightly better in Algeria than in France. Medical and social support seems to be quantitatively less important in Algeria. PMID- 2576965 TI - Japanese encephalitis in Indonesia. PMID- 2576966 TI - Vectors of Japanese encephalitis virus (JEV): species complexes of the vectors. AB - The vectors of JEV are Cx. tritaeniorhynchus, Cx. vishnui, Cx. pseudovishnui, Cx. gelidus, Cx. fuscocephala, Cx. quinquefasciatus, Cx. pipiens pallens, Cx. bitaeniorhynchus, Cx. annulirostris, Aedes togoi, Ae. japonicus, Ae. vexans nipponii, Anopheles annularis and An. vagus. Cx. tritaeniorhynchus is in the tritaeniorhynchus complex, breeds in rice fields, ground pools in vast areas. Two types of mating behavior, eurygamy and moderate stenogamy were detected. In the case of the eurygamy type, the mosquitoes were from Southern Thailand and hilly areas near Kanchanaburi, Thailand. Female mosquitoes are usually dark in color, the cibarial armature has rod teeth and the posterior end of the cibarial armature is bowl shaped with a typical rim. The rim of the bowl is everted. The moderate stenogamy type were mosquitoes from the plain areas such as Bangkok, Ayutthaya, Suphan Buri and Saraburi. The posterior end of the cibarial armature is bowl shaped with a stout rim. The larvae were characteristic in their siphon index, antennal index, hair O of prothoracic segment, and comb scale number and arrangement. Cx. tritaeniorhynchus summorosus from Japan, Los Banos and Luzon, Philippines, differed from Cx. tritaeniorhynchus in that on the lateral plate of the phallosome tritaeniorhynchus teeth are somewhat weakly developed and only gently curved whereas in tritaeniorhynchus summorosus they are strongly developed, considerably longer, and sharply recurved. The siphons of larvae are short, the sides parallel and the apex truncate in tritaeniorhynchus whereas in tritaeniorhynchus summorosus they are long and slender. Cx. tritaeniorhynchus var. siamensis is possibly present. Colonies have been maintained in the Department of Medical Entomology for 31 generations. The characteristics are in hair O (short, less than 20 branches, and without secondary branching and the larval siphon (short and broad where the others are long). Cx. vishnui and Cx. pseudovishnui are in the vishnui complex. Cx. quinquefasciatus and Cx. pipiens pallens are in the Cx. pipiens complex comprising: (1) Cx. pipiens; (2) Cx. quinquefasciatus Say; (3) Cx. molestus Forskal; (4) Cx. pipiens pallens; (5) Cx. australicus; (6) Cx. globocoxitus. Anopheles annularis is a species complex evidenced by two types of polytene chromosomes. PMID- 2576967 TI - Studies on Japanese encephalitis vectors in Indonesia. AB - Entomologic surveys indicated that JE vectors in Indonesia are Cx. tritaeniorhyncus and Cx. gelidus. In most study areas, the former were predominant among all the culicine mosquitoes. The seasonal abundance of the two JE vector species was correlated significantly with the rainfall. The virus activity was parallel to the seasonal fluctuation of the vectors suggesting that the transmission of the disease would depend on the population dynamics of the vectors. PMID- 2576968 TI - Strategies for control of Japanese encephalitis mosquito vectors in the Philippines rice fields. PMID- 2576969 TI - Japanese encephalitis vectors in Thailand during 1978-1985. PMID- 2576970 TI - Feasibility of wing beat sound trap for the control of mosquito vectors. AB - Early observations suggested that the female sound was a possible cause of mating. Attempts had been made for introduction of female wing beat sound for removal male mosquitoes from the population for the control purpose. The traps emitted female wing beat sound, were set on black clothes as a swarm marker, could collect a large number of male Cx. tritaeniorhynchus in Japan. Those traps were later improved with introduction of two attractants, hamster and dry ice. Consequently, two systems were adopted for efficiency trapping of males and females. A cylinder trap with 350 Hz of wing beat frequency was introduced for male Cx. tritaeniorhynchus collection, while the cage trap with 530 Hz was for female collection. The traps were set every other days after sun set for three weeks in a paddy field. Although there was no decrease of population density, the reduction of parous rate was evident. For future effective control, it may suggest the need to distribute more wing beat sound traps to cover all larva breeding paddy field and near by blood sources. On the other hand, other control methods should be integrated. PMID- 2576971 TI - Orthodontic silver brazing alloys. AB - Orthodontic silver brazing alloys suffer from the presence of cadmium, excessive flow temperatures, and crevice corrosion on stainless steel. Seven alloys were examined. Two alloys contained cadmium. The lowest flow temperature observed was 629 degrees C for a cadmium alloy and 651 degrees C for two cadmium free alloys. Three alloys had corrosion resistance superior to the other solders. Addition of low melting temperature elements gallium and indium reduced flow temperature in some cases but produced brittleness in the brazing alloy. PMID- 2576972 TI - In vitro multidrug resistance of P388 murine leukemia selected for resistance to diaziquone. AB - P388 leukemia sublines were isolated from leukemia-cell-bearing CD2F1 mice that had been treated in vivo with increasing amounts of diaziquone (AZQ). The sublines isolated for in vitro studies were AZQ19 and AZQ30 which corresponded to the 19th and 30th in vivo passages, respectively. The AZQ19 subline displayed a very low degree of resistance to AZQ (1.5-fold), whereas the AZQ30 subline was sensitive. Both sublines, however, had much higher degrees of resistance to Adriamycin than to AZQ (24-fold for AZQ30 cells and 10-fold for AZQ19 cells). Both cell lines were also more resistant to actinomycin D, colchicine, and vincristine than to AZQ. The AZQ19 line was resistant to the alkylator thio-TEPA to the same degree that it was to AZQ, but the AZQ30 line was sensitive to thio TEPA. On the other hand, AZQ30 cells were resistant to hydrogen peroxide with a very low degree of resistance (1.27-fold, P less than 0.05), whereas the AZQ19 line was sensitive. Drug accumulation experiments indicated that AZQ-resistant cells differed from the parental line in that they did not accumulate Adriamycin or vinblastine. In the case of AZQ, however, resistant and parental lines accumulated the same amounts of exchangeable AZQ. Using the immunoblotting technique, no P-glycoprotein was found in resistant cells. The resistant lines consumed oxygen at greater rates than the parental line. Oxygen consumption (Mean +/- SD) in sensitive cells was 2.0 +/- 0.4% O2 consumed/min, whereas in resistant cells it was nearly 3.1 +/- 0.6% O2 consumed/min. The increase in oxygen consumption with drug resistance was statistically significant (P less than 0.01). The kinetics of production of hydroxyl free radicals and of AZQ free radicals were faster in the resistant lines reflecting, in essence, their increased oxygen consumption. It appears that the two sublines analyzed here show resistance mechanisms that may have been elicited by the two distinct chemical constituents of AZQ. Therefore, in the AZQ19-resistant line, the alkylating aspect of AZQ was emphasized, whereas in the AZQ30 line, the quinone and, thus, free radical aspect was emphasized. This is consistent with AZQ30 cells being sensitive to the alkylator thio-TEPA and resistant to hydrogen peroxide, and the AZQ19 line being resistant to thio-TEPA and sensitive to hydrogen peroxide. In addition, the AZQ30 cell line was relatively more resistant than the AZQ19 line to Adriamycin. PMID- 2576973 TI - Progressive resistance to doxorubicin in mouse leukemia L1210 cells with multidrug resistance phenotype: reductions in drug-induced topoisomerase II mediated DNA cleavage. AB - Cells selected for resistance to doxorubicin (DOX) express the multidrug resistance (MDR) phenotype, and resistance has been suggested to be due primarily to enhanced cellular efflux of drug. A progressively DOX-resistant (10- and 40 fold) L1210 mouse leukemia model system, which does not exhibit enhanced DOX efflux as a primary mechanism of resistance, was found to display the MDR phenotype, based on overexpression of P-glycoprotein in western blots and cross resistance to vinca alkaloids. Cross-resistance to another topoisomerase II inhibitor, etoposide (VP-16), was similar to that of DOX (10- and 40-fold), whereas resistance to N-[4-(9-acridinylamino)-3-methoxyphenyl]methanesulfonamide (m-AMSA) was 5-fold lower. In contrast, no cross-resistance to camptothecin, an inhibitor of topoisomerase I, was observed. Topoisomerase II decatenation activity in nuclear extracts from 10- and 40-fold DOX-resistant cells was 2- and 4-fold lower, respectively, when compared to sensitive cells. In these cells, however, marked reductions in m-AMSA- and VP-16-induced topoisomerase II mediated DNA cleavage were found to exceed decreases in the catalytic activity of the enzyme. Results from this study demonstrated that, in progressively DOX-resistant L1210 mouse leukemia cells with the MDR phenotype, a better relation existed between the degree of resistance and reduced VP-16- and m-AMSA-induced topoisomerase II mediated DNA cleavage, than between increases in P-glycoprotein and concomitant reduction in DOX accumulation. PMID- 2576974 TI - Modulation of drug resistance in a daunorubicin resistant subline with oligonucleoside methylphosphonates. AB - Human K562 erythroleukemia cells were selected in sequential steps for resistance to daunorubicin (K562/III) and found to be cross-resistant to a number of drugs, including vincristine, dactinomycin, doxorubicin, etoposide, and teniposide. In this paper, we report that the K562/III subline showed amplification of an mdr1 gene and its 4.5 kb transcript. Our results also show that non-ionic oligonucleoside methylphosphonates, complementary to the initiation codon and 15 bases upstream of the mdr1 gene, can completely inhibit the synthesis of P glycoprotein and partially increase the toxicity of daunorubicin. PMID- 2576975 TI - Protein phosphorylation in multidrug resistant Chinese hamster cells. AB - Protein phosphorylation is altered in multidrug resistant, reverse transformed Chinese hamster cells selected for resistance to vincristine (DC-3F/VCRd-5L) or actinomycin D (DC-3F/AD X), as compared to drug-sensitive parental DC-3F cells. Evidence for this was obtained by gel electrophoretic analysis of proteins phosphorylated in vitro in the presence of [gamma -32P]ATP. In general, the level of incorporation of 32P into resistant cell proteins was higher than into proteins of sensitive cells, when reactions were carried out in either the presence or absence of exogenous protein kinase modulators. Phosphorylation of P glycoprotein a multidrug resistance-related protein, and of sorcin, a 22 kDa calcium-binding protein overproduced in many multidrug resistant cells including DC-3F/VCRd-5L, was demonstrated. Analysis of proteins metabolically labeled with [32P]-orthophosphate suggests that protein phosphorylation differences in cell free extracts are representative of events in the intact cells. Data support the probability that a variety of kinase and/or phosphatase activities were altered in the multidrug resistant cells. These may be associated with resistance development, P-glycoprotein function, reverse transformation, state of differentiation, inhibition of cellular proliferation, or all of these components. PMID- 2576976 TI - Cloning of the cDNA and sequence of the human proliferating-cell nucleolar protein P120. AB - The 120 kDa proliferating-cell nucleolar antigen described by Freeman et al. (Cancer Res. 48:1244; 1988) is the most cancer specific of the proliferation associated nucleolar proteins identified thus far. It is localized in a novel nucleolar microfibrillar structure recently described by Ochs et al. (Cancer Res. 48:6523; 1988). The amino acid sequence has been determined by a combination of cDNA and genomic DNA sequences. This molecule contains, consecutively, four major domains: a basic domain, an acidic domain, a hydrophobic and methionine-rich domain, and a domain rich in cysteine and proline residues. The isolated cDNA was shown to code for the HeLa P120 protein as shown by a similarity in immunoreactivity, mobility on sodium dodecylsulfate-polyacrylamide gel electrophoresis, and patterns of partial digestion of the Escherichia coli expressed P120 and the HeLa nucleolar P120 protein. This protein is of special interest because it is expressed in early G1 and, in studies to date, it has not been detected in benign tumors and most normal resting tissues. PMID- 2576977 TI - Proteolytic processing in endosomal vesicles. PMID- 2576978 TI - A TCR gamma delta cell recognizing a novel TL-encoded gene product. PMID- 2576979 TI - Proteolytic activity in black-pigmented bacteroides species. AB - Black-pigmented Bacteroides species are frequently found in dentoalveolar abscesses. One general mechanism of bacterial virulence is the production of extracellular enzymes which degrade connective tissue or molecules associated with host defense. In this study the proteolytic activity of 18 bacterial strains from 9 black-pigmented Bacteroides species was examined. Bacteroides gingivalis degraded the greatest number of substrates studied and produced the highest levels of enzymatic activity. B. gingivalis was the only species that degraded collagen and produced high levels of enzymes that degraded N-benzoyl-DL-arginine (BANA) and N-CBz-glycyl-glycyl-arginine. Bacteroides intermedius degraded several substrates including PZ peptide. Bacteroides endodontalis produced enzymes that degraded beta-naphthylamide derivatives of glycylproline and glycylphenylalanine. There were considerable differences in enzyme production between strains of the same species. Such heterogeneity between strains in the production of proteolytic enzymes may be relevant to the in vivo infections produced in the host. PMID- 2576980 TI - A comparison of marker proteins in precancerous lesions of oral mucosa and liver. PMID- 2576981 TI - [Researches on the forensic application of DNA probe. I. The determination of paternity and the identification of individual using PYNH24 probe]. AB - Restriction fragment length polymorphism of genomic DNA digested with MspI was analyzed using specific probe PYNH 24. The clear and readable patterns were obtained. Of 190 unrelated individuals tested, the polymorphism is 95%. Inheritance of alleles in 45 related individuals of 8 families is consistent with Mendelian Law. PMID- 2576982 TI - Human breast carcinoma cell levels of MDR-1 (P-glycoprotein) transcripts correlate in vivo inversely and reciprocally with tumor progesterone receptor content. AB - Sixteen human breast carcinomas were subjected to molecular biological and biochemical analyses to determine tumor cell MDR-1 (P-glycoprotein) levels and progesterone receptor content. The results of these analyses disclosed a strong reciprocal and inverse correlation between levels of tumor cell-specific MDR-1 complementary hybrids and progesterone receptor content. These results suggest that the mechanisms which control expression of the P-glycoprotein gene and the progesterone receptor are interrelated and antagonistic, a result with obvious molecular biological, physiological, and clinical implications. PMID- 2576984 TI - Welding implants in the mouth. PMID- 2576983 TI - Gimlet implant system and intra-oral welding. AB - An experienced implantologist introduces a new, flexible, and versatile endosteal implant system. Requiring only a single bur, the implant may be used immediately or permitted to osteointegrate. Since intra-oral welding techniques may be used, parallelism of implants is not a requisite for the successful completion of mesiostructure double-railed bars. A variety of prosthetic techniques may be incorporated into the Gimlet system, and the implants themselves can be used in a number of locations and employed for multiple purposes. PMID- 2576985 TI - [DNA diagnosis of hereditary diseases]. PMID- 2576987 TI - [Sterile conditioning of sealed PETP foil for hot air sterilization (dry heat)]. PMID- 2576986 TI - [Effect of metipranolol on the cardiovascular system of the rabbit in vivo during spontaneous and paced heart rhythm]. AB - The effects of i.v. administration of metipranolol (Trimepranol, Biotika; 0.03; 0.15 and 0.3 mg.kg-1) and saline (1.0 ml.kg-1) on the cardiovascular system of rabbits in vivo have been determined under the conditions of the paced and non paced heart. The administration of saline in the control group led to a mild decrease of dP/dtmax, minute blood flow through the abdominal aorta and slowing down the cardiac frequency without significant changes in blood pressure in a. femoralis and stroke blood flow through the abdominal aorta. No practically important differences between the paced and non-paced conditions were found. The administration of Trimepranol led to a significant, dose dependent decrease in dP/dtmax, which was less expressed in the paced heart (in comparison with the non paced heart) after the lowest dose of the drug; no such a difference was found after higher doses of Trimepranol. Reactions of blood pressure (no significant changes) and minute blood flow through the abdominal aorta (a mild decrease) to the administration of Trimepranol were similar both in the paced and in non-paced heart. A significant slowing-down of the spontaneous cardiac frequency after Trimepranol was dose-dependent and, in relation to this fact, a significant increase in stroke blood flow through the abdominal aorta was found. On the basis of the above-mentioned results, it is possible to conclude that the paced heart conditions do not unfavourably influence the effects of Trimepranol on the cardiovascular system of rabbits in vivo. PMID- 2576988 TI - Effects of alpha 1-adrenoceptor blocker prazosin on microcirculation in terminal rabbit ileum. AB - The influence of the specific alpha 1-blocker prazosin on the microcirculation of the terminal ileum was examined in 10 rabbits. For this purpose an isotope clearance test was carried out by administering 133-Xenon solution into the intestinal wall before and after the intra-arterial injection of prazosin (1.0 mg) via the superior mesenteric artery. These experiments were supplemented by haemodynamic and thermographic measurements in a further group of 5 rabbits. Due to the systemic circulatory effect of prazosin, i.e. the drug-induced hypotension, the bowel segment exhibited, contrary to expectations, significantly delayed values for isotope elimination indicating a reduced local tissue clearance and blood supply. Thermographic observations also confirmed the impairment of mesenteric blood flow after prazosin. Therapeutic applicability of alpha 1-adrenoceptor blockers to treat intestinal circulatory disturbances in diseases of vascular genesis thus remains dubious. PMID- 2576991 TI - [Human rights and psychiatry]. PMID- 2576989 TI - Effects of somatostatin on intestinal circulation and oxygen consumption. AB - The effects of intraarterial administration of somatostatin upon intestinal blood flow, intestinal capillary surface area, oxygen consumption and intestinal motor activity were measured in anesthetized dogs. Blood flow to the segment of distal ileum was measured with an electromagnetic blood flow meter, and arteriovenous oxygen difference (AVO2) was determined spectrophotometrically. Intestinal oxygen consumption was calculated as the product of AVO2 and total blood flow. The clearance of 86Rb was measured to estimate the density of the perfused intestinal capillaries. Changes in blood flow distribution were estimated from the distribution of radiolabelled microspheres. Intestinal motor activity was monitored from changes in intraluminal pressure. Somatostatin induced a dose related decrease in intestinal blood flow, capillary surface area and intestinal oxygen consumption. A significant increase in intestinal motor activity was also observed. The data of this study indicate that somatostatin acts on smooth muscle of both arterioles and precapillary sphincters and results in a potent vasoconstriction in the intestinal microcirculation. PMID- 2576990 TI - [Haloperidol decanoate: results of a 6-month open trial in paranoid schizophrenia]. AB - An open clinical trial with Haloperidol Decanoate was carried out in order to determine its therapeutic efficacy, side effects, and tolerance. The sample population was a 30 male-and-female-psychotic-patient group (15 in-patients and 15 out-patients treated at a private psychiatric institution). A marked stabilizing effect with no relapses was observed. Therefore, it can safely be said that Haloperidol Decanoate helped in controling these patients satisfactorily, and getting a positive social reintegration. PMID- 2576993 TI - Oncogenes. PMID- 2576992 TI - Oncogenes and proto-oncogenes: general concepts. PMID- 2576996 TI - The platelet-derived growth factor system. PMID- 2576995 TI - The epidermal growth factor receptor and its ligands. PMID- 2576994 TI - src-related protein tyrosine kinases. PMID- 2576997 TI - Transforming growth factors-alpha and -beta and their potential roles in neoplastic transformation. PMID- 2576998 TI - Oncogenes in human solid tumors. PMID- 2576999 TI - Oncogenes in human leukemias and lymphomas. PMID- 2577000 TI - Molecular biology: concepts and techniques. PMID- 2577001 TI - Human retrovirus-associated malignancy. PMID- 2577002 TI - The human DNA tumor viruses: human papilloma virus and Epstein-Barr virus. AB - HPV and EBV are common infectious agents that persist after primary infection in a latent state with occasional shedding of virus. Therefore, one of the fundamental questions in the etiology of those cancers that are linked to infection with such ubiquitous viruses is why cancer develops in a few people when many are infected. Because only a small subset of infected people will develop specific cancers, it has been suggested that the presence of the viral genomes in the malignancies merely indicates a persistent or latent infection. However, if the viral infection was not an etiologic factor in the development of the specific cancers, then one would predict that the proportion of cancers that contained the viral genome would reflect the proportion of infected people and that the same cancers could develop in uninfected people. The sporadic detection from nonendemic areas of Burkitt's lymphoma without EBV initially suggested that EBV infection was not etiologic. However, the rate of incidence of BL in infected populations of children is disproportionately greater than the very low incidence in uninfected children, which suggests that EBV infection is an important contributing factor. Moreover, the development of EBV-induced lymphomas in the immunocompromised and the consistent detection of EBV in specific epithelial malignancies such as NPC suggest that EBV infection is essential in the induction of specific cancers. Similarly, the consistent detection of particular HPV types in certain types of cancer suggests that HPV is also an etiologic factor. There are several strikingly similar aspects of infection with HPV and EBV. In latent infection, both of the viral genomes persist as an extrachromosomal episome with an origin of replication that is activated by binding to a virally encoded polypeptide. The state of viral infection appears to be linked with the state of cellular differentiation such that latent infections are activated into a replicative state as the cells differentiate. Moreover, elevated levels of expression of the putative transforming genes are linked to transformation. However, perhaps most importantly, the malignancies are clonal with regard to the viral infection; HPV-associated malignancies have unique integrative events and EBV-associated malignancies have clonal episomal forms. This reveals that the specific cancers are clonal cellular proliferations that developed after viral infection. In vitro, the initially polyclonal cell lines produced by EBV infection rapidly evolve to oligoclonality or monoclonality. This could be due to a slightly faster rate of growth such that the progeny of one clone rapidly predominate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2577004 TI - Therapeutic applications of oncogenes. PMID- 2577003 TI - Molecular biology of the human retinoblastoma gene. PMID- 2577005 TI - The myc family of nuclear proto-oncogenes. AB - Several members of the myc family of proto-oncogenes have been described, and some (c-, N-, and L-myc) have been characterized in considerable detail. They are united by a common gene structure and nucleotide homologies that were used to identify some of them initially. Their protein products also have scattered regions of amino acid identity or homology. Although the cellular activities of the various proteins are unknown, some members may play a role in regulating cell growth and differentiation. They share the ability to cooperate with an activated ras gene and cotransform embryonic rodent cells. In naturally occurring tumors, the members of the myc family of oncogenes appear to be activated by genetic changes (proviral insertion, chromosomal translocation, and gene amplification) that augment or otherwise disrupt normally regulated expression. The members of this family of genes differ markedly in their tissue specificity and developmental regulation of expression. This may account in part for the frequent appearance of activated c-myc genes in a wide variety of neoplasms and the limited appearance of activated N- and L-myc genes in tumors of embryonic or neural origin. The c-myc gene may be activated in tumors by a variety of mechanisms, whereas N- and L-myc appear to be activated only by gene amplification. Regulation of expression of the different myc genes also appears to occur by different mechanisms. Finally, the products of the different genes differ in may regions of the protein, and this divergence probably reflects their specific and individual functions. PMID- 2577006 TI - The ras family of oncogenes. PMID- 2577007 TI - Studies on histaminergic compounds, Part VII. Histamine H2-binding on guinea-pig cerebral cortex compared to histamine (ant)agonism. AB - The pKD values of series of H2-active compounds, obtained from displacement curves of 3H-tiotidine from a guinea-pig cerebral cortex homogenate were compared with the pA2/pD2 values of these compounds on the right atrium of the same animal species. A good correlation was found between the cortex pKD value and the pharmacological activity on the right atrium, especially with the antagonists, the partial agonists and the agonistic impromidine analogues (guanidines). The poor correlation between cortex pKD and atrium pD2 of some other agonists (the amines) might be explained by the presence of spare receptors for these compounds. The different number of spare receptors for the guanidines and the amines might be explained by the differences in base strength of these compounds. PMID- 2577008 TI - Characterization of rat cerebral cortical beta adrenoceptor subtypes using (-) [125I]-iodocyanopindolol. AB - (-)-[125I]-Iodocyanopindolol [-)ICYP), used to characterize beta adrenoceptors on membrane preparations from rat cerebral cortex, was shown to have affinity for both beta adrenoceptors and serotonin receptors. Therefore, 10 microM serotonin was added to the assays to prevent (-)ICYP binding to serotonin receptors. Under these conditions, (-)ICYP binding to the cortical membrane preparation was reversible and saturable, and the association reaction was very slow. The dissociation reaction was also very slow, and revealed two affinity states corresponding to a high and a low affinity state. Scatchard analysis showed a single class of binding sites with an equilibrium dissociation constant (KD) of 20.7 pM, and a maximal density of binding sites (Bmax) of 95.1 fmol/mg membrane protein. Displacement binding analyses revealed a potency series of (-) isoproterenol greater than (-) epinephrine equal to (-) norepinephrine, suggesting a predominance of the beta 1 adrenoceptor subtype. Detailed competition ligand binding studies with the selective beta 1 adrenoceptor antagonist ICI-89406 and the selective beta 2 adrenoceptor antagonist ICI-118551, showed that about 70% of the beta adrenoceptor population in the rat cortex is of the beta 1 subtype with the remainder being of the beta 2 subtype. We conclude that since (-)ICYP binds to both beta adrenoceptors and serotonin receptors, it is important to prevent the binding of (-)ICYP to serotonin receptors by adding a suppressing ligand like excess cold serotonin when assaying beta adrenoceptors. We have presented the first such characterization of rat cerebral cortical beta adrenoceptors with (-)ICYP in this study. PMID- 2577009 TI - [HLA and disease in Argentina. Serologic and genomic polymorphism]. AB - In this report we discuss the results of the association of chronic active hepatitis (B virus) and coeliac disease with HLA class I and class II antigens, in patients of Latin American Caucasian origin. Evidence is presented showing that the alleles involved differ from those reported in other Caucasian populations of different ethnic background. Differences were observed both at the serology and at the DNA (RFLP) level. The relevance of these findings regarding the clinical implications as well as the molecular mechanisms involved in the associations are discussed. PMID- 2577010 TI - [Entomologic situation regarding arbovirus circulation in the Guajaibon area]. AB - The collections of culicidae made in the Guajaibon area, North coast of Havana province, are analyzed with arbovirologic purposes. The predominance of Aedes scapularis in the human bait collections is confirmed. The possibility of arbovirus circulation in the area is suggested. PMID- 2577012 TI - [Immunobiological arguments favoring regional treatments in cancer]. PMID- 2577011 TI - [The detection and treatment of asymptomatic myocardial ischemia to reduce morbidity and mortality from ischemic cardiopathy]. AB - The paper reports and assesses the most topical data having led to delimiting the asymptomatic myocardial ischemia as the most precocious form of manifestation of ischemic cardiopathy. The role of asymptomatic myocardial ischemia involvement in angina pectoris, myocardial infarction and serious arrhythmias leading to sudden cardiac death are also underlined from the viewpoint of prognosis severity. Likewise, the authors discuss; the prevalence of asymptomatic myocardial ischemia as a distinct manifestation form of myocardial ischemia; the way of selecting the cases; the anti-ischemic treatment that gave good results in diminishing morbidity and mortality induced by ischemic cardiopathy. PMID- 2577013 TI - [Digestive manifestations during systemic scleroderma]. AB - A 3 years' study was performed on a group of 32 patients with systemic scleroderma. 23 of them had digestive manifestations involving the whole digestive tract. The diagnosis was based on the clinical, radiological, echographic, endoscopic and anatomopathological examinations. In the prolonged forms of the disease, successive associations appeared in various segments of the digestive tract, the esophageal one being always the first. In all cases, the digestive manifestations followed the cutaneous involvement and were constantly correlated to Raynaud's syndrome presence. Digestive manifestations did not influence the prognosis of the substrate disease. PMID- 2577014 TI - [The bioavailability of nifedipine in different solid pharmaceutical preparations for oral use]. AB - The paper reports on the bioavailability of niphedipine in various pharmaceutic preparations administered in a single dose of 10 mg, per os, to volunteer subjects: Niphedipine dragees (Terapia, Cluj-Napoca), Adalat capsules (Bayer); Adalat coated tablets (Bayer and Birlasik Alman Ilac Fabricalari, Istanbul) and Corinfar dragees (VEB Arzneimittelwerk, Dresden). In the blood samples collected, niphedipine was determined by a gas-chromatographic procedure. Pharmacokinetic analysis of the experimental data was made by a digital computer. Bioavailability of niphedipine was the best with Adalat capsules. The relative bioavailability of the other products was: tablets (Adalat); 93%; dragees (Niphedipine): 92%; dragees (Corinfar 86%). Absorption speed of Niphedipine decreases in the order: capsules, tablets, indigenous and imported dragees. Statistical analysis (Student test) shows that the differences in bioavailability among the preparations are not important. Efficiently therapeutic plasmatic concentrations are maintained for about 6 hours after a single dose of 10 mg administered as tablets and dragees and for 8 hours in the case of capsules. Important differences exist between the maximum concentration of niphedipine in blood, following some differences in the absorption speed, achieved after administration of capsules, on the one hand, and of tablets and dragees on the other hand. Choosing the type of tablet depends, therefore, on the nature of the affection treated. Niphedipine (Terapia) has corresponding biopharmaceutic properties and is useful in treating hypertension and for preventing and treating anginal attacks. PMID- 2577016 TI - [An echocardiographic evaluation of pure and isolated mitral stenosis. Comparisons with other noninvasive methods]. AB - In 94/116 (81%) cases of pure and isolated mitral stenosis (MS), ECO-2D permitted the correct determination of the surface of the mitral opening (SMO). The cases were divided in terms of the SMO size into: extended MS (SMO greater than 2 cm2, n = 28), moderate MS (SMO between 1.1 and 2 cm2, n = 54), and narrow MS (SMO less than or equal to 1 cm2, n = 12). The SMO size influenced significantly the values of several noninvasive indices of the MS severity: the Wells index, the 2-C1DM noise interval, the NYHA class, the cardiothoracic index (expressed as an average, the +/- standard deviation for each group), and also the incidence of the atrial fibrillation, AQRS greater than or equal to 70 degrees, of the radiographic aspect of the pulmonary stasis or of the right cardiac failure (given in percent for each group). Anyhow, none of these parameters, taken alone, permitted the correct assessment of the MS severity. The sensibility, specificity and predictive value of the above-mentioned criteria were not sufficient for the detection of the narrow MS (SMO less than or equal to 1 cm2). ECO-2D is the most exact noninvasive method for appreciating the anatomical state of the mitral valvular apparatus in MS and for selecting the patients for the surgical correction. PMID- 2577015 TI - [The treatment of hypertensive crisis with nifedipine as the basis]. AB - In 48 patients (p) with hypertensive crisis (HC) the effect of nifedipine (N) sublingual 10-20 mg alone (group I, n = 19, mean control AH +/- SD 232 +/- 15.3/132.5 +/- 4.9 mmHg) or associated with furosemide and clonidine (group II, n = 29, AT 249 +/- 21/131.8 +/- 13.6 mmHg). In both groups the AT fell significantly starting five minutes after the administration of N (except diastolic AT in group II); the values measured at 45 min. being 177 +/- 32/105.4 +/- 13 mmHg in group I and 164.6 +/- 44.4/100.1 +/- 16.3 mmHg in group II (the mean proportional difference at 45 min. for systolic AT was 24.6 +/- 11.4% in group I and 28.7 +/- 12.2% in group II; for diastolic AT 20.5 +/- 9.4% in group I, and 27 +/- 12.2% for group II). The good clinical results consisted of lowering of the AT values below critical levels and clinical improvement in 42 p (87.5%). Tolerance to N was good, in a single case was hypotension associated with fainting, both being promptly treated by simple means. CONCLUSIONS. 1. N administered sublingual, 10-20 mg, alone or associated with furosemide has in most patients a rapid hypotensive effect, lowering AT below critical limits within 45 min; 2. the drug is readily administered and without the risk of side effects and can be used in the field in the emergency treatment of hypertension. PMID- 2577017 TI - [Sudden death from coronary thrombosis and myocardial infarct correlated with blood alcohol]. AB - The authors analyze the medicolegal files including 3,786 consecutive autopsies, of which 402 sudden coronary cardiac deaths. Autopsy was completed by histologic examination and toxicologic tests (alcoholemia). In the category of coronary cardiac sudden deaths there were 53 coronary thromboses (13.2%) and 36 recent myocardial infarction (8.95%). In 1,196 (31.6%) of 3,786 alcoholemia determinations the results were positive in 111 (27.6%), the difference between the two frequencies not being statistically significant (t less than 1.96). Alcoholemia was positive in 6 of 53 cases of coronary thromboses (11.3%, p less than 0.01), and in 36 cases of recent myocardial infarction alcoholemia was positive in 7 cases (19.5%; t less than 1.96). PMID- 2577018 TI - [The relations between the morphology of the postresection gastric stump after a gastroduodenal ulcer and the dumping syndrome]. AB - Of a group of 272 patients subjected to gastric resection for gastric-duodenal ulcer, the "dumping" syndrome was found in 46 (17%). The most frequent (39.7%) was in the Reichel-Polya anastomosis type and the less frequent (9%) in pyloroplasties. The test of induced hyperglycemia by ingesting 15 g/kg body glucose did not show differences in the values of the maximum glycemia in the patients with the "dumping" syndrome versus the other group. The surface of the anastomosis opening and the length of the gastric stump were appreciated with a central imaging endoscope. The surface of the anastomosis opening was found larger in those with a "dumping" syndrome and Reichel-Polya's resection, although the differences are not statistically significant; likewise, there seems to be a less length of the gastric stump and a higher weight difference in those with the "dumping" syndrome. The lack of pyloric sphincter seems to be very important in producing the "dumping" syndrome due to the fact that the alimentary bolus is not fractionated and its sequential evacuation in duodenum and jejunum does not take place. PMID- 2577019 TI - [Splenic lymphosarcoma evolving under the mask of Banti's syndrome]. PMID- 2577021 TI - [AIDS: a challenge to health policy and the law]. PMID- 2577020 TI - [Loxoscelism in Chile. Epidemiologic, clinical and experimental studies]. AB - A panoramic sight of epidemiological, clinical and experimental studies, referring to Loxosceles laeta and loxoscelism, carried out in 1955-1988, in Santiago, Chile is presented. Two-hundred and sixteen cases of loxoscelism were studied. The most relevant features were: 84.3% corresponded to cutaneous loxoscelism (CL) and 15.7% to viscerocutaneous loxoscelism (VCL); 73.6% occurred in hot season; in 86.6% of cases the accident happened in the house, particularly in bedrooms, while the people were sleeping or dressing. The spider was seen in 60.2% of cases and identified in the laboratory as L. laeta in 10.6% of all cases. The sites more frequently bitten were the limbs with 67.6%; a burning stinging was the most frequent initial symptom. Pain, edema and livedoid plaque, which developed later into a necrotic eschar, were the predominant local manifestations. In VCL, hematuria and hemoglobinuria were constant, while jaundice, fever and sensorial involvement were present in most of the cases. CL patients were parenterally treated with antihistaminic drugs or corticoids, while VCL ones were treated with corticoids by injection. The condition of patients in the last follow up was: complete cure in 75.5%, cure with a scarfed sequela in 8.3%, death in 3.7% (all VCL) and abandonment in 12.5%. Additionally, a series of experimental studies, both in vivo and in vitro, has been performed in order to clarify basic aspects on L. laeta venom and the treatment of loxoscelism. PMID- 2577022 TI - [Traumatic injuries of the teeth]. PMID- 2577023 TI - The biology of human CD2. PMID- 2577024 TI - Structure-function relationships of the human T lymphocyte CD2 antigen. PMID- 2577026 TI - [Periosteal reaction in periarteritis nodosa in children]. AB - Bone involvement has exceptionally been reported in children with periarteritis nodosa. A 5-year old girl was admitted to hospital for fever and arthralgias. Three months later, myalgias and painful subcutaneous nodules developed on the legs and ankles. Skin biopsy yielded a diagnosis of periarteritis nodosa. X-ray films revealed a bilateral periosteal reaction with images of laminae in the tibia and fibula. After a 4-year remission under corticosteroid therapy, the periosteal reaction persisted. PMID- 2577025 TI - Structure and regulation of the leukocyte adhesion receptor LFA-1 and its counterreceptors, ICAM-1 and ICAM-2. PMID- 2577027 TI - [Lymphadenopathy due to sulfasalazine in rheumatoid polyarthritis]. PMID- 2577028 TI - [Treatment of chronic coronary insufficiency]. PMID- 2577030 TI - [Dental injuries and their endodontic implications]. PMID- 2577029 TI - [Pathophysiological analysis of rapidly progressive periodontitis]. AB - Pathophysiological features were studied on 7 patients with rapidly progressive periodontitis but without any evidence of systemic disease, to analyse the clinical pathogenesis. The patients consisted of 5 females, 2 males, between the ages of 32 and 42 years. All patients had severe and rapid alveolar bone destruction on the basis of radiographic measurement. Abnormal serum levels of IgG and IgM were detected in some patients. Higher IgG level was found in 4 patients and higher IgM level was found in 2 patients. The proportion of lymphocyte subsets was calculated in mononuclear cells from peripheral blood of patients. Higher OKT4/OKT8 ratio was found in all patients. The percentage of OKT4 positive cells in 2 patients was higher than that in normal subjects while the percentage of OKT8 positive cells in 4 patients was lower than that in the healthy controls. Microorganisms from periodontal pockets were examined in 5 patients. Bacteriodes was isolated in all 5 patients and Haemophilus actinomycetemcomitans in 2 patients. PMID- 2577031 TI - Clinical effectiveness of analgesics in chronic pain states. PMID- 2577032 TI - Use of the formalin test in evaluating analgesics. PMID- 2577034 TI - Clinical implications of PCP, NMDA and opiate receptors. PMID- 2577033 TI - Cerebral pathways activated by PCP-like compounds: relevance to neurotransmitters and their receptors. PMID- 2577035 TI - Novel [D-Pen2, D-Pen5]enkephalin derivatives with increased sigma receptor potency and selectivity: potential tools for opioid pharmacology. PMID- 2577036 TI - Intracerebroventricular (ICV) clonidine produces an antianalgesic effect through spinal dynorphin A(1-17) mediation. PMID- 2577037 TI - Characterization of dynorphin A(1-17)-induced place preference in rats. PMID- 2577039 TI - Comparison of the behavioral and neurochemical effects of 5,7-DHT, MDMA and D,L fenfluramine. PMID- 2577038 TI - Psychostimulant properties of MDMA. PMID- 2577041 TI - The association between non-recreational benzodiazepine use and other substance abuse. PMID- 2577040 TI - Relative abuse liability of benzodiazepines in methadone maintained populations in three cities. PMID- 2577042 TI - Sedative/tranquilizer use and abuse in alcoholics currently in outpatient treatment: incidence, pattern and preference. PMID- 2577043 TI - Oral naloxone treatment of narcotic induced constipation: dose response. PMID- 2577045 TI - Can buspirone substitute for benzodiazepines in all anxious patients? PMID- 2577044 TI - Responses to i.v. L-tryptophan in MDMA users. PMID- 2577046 TI - Abuse liability of diphenhydramine in sedative abusers. PMID- 2577048 TI - Effects of D1 and D2 dopamine antagonists on heroin-trained drug discrimination. PMID- 2577047 TI - Effects of buspirone in the benzodiazepine dependent rat. PMID- 2577049 TI - MK-801 attenuates the methamphetamine induced decreased in tryptophan hydroxylase activity. PMID- 2577050 TI - One-trial conditioned rotation in rats. PMID- 2577051 TI - Opioid dependence after continuous intrathecal infusion of mu and delta opioids in the rat. PMID- 2577052 TI - Pain modulation: opiates and chronic pain. PMID- 2577054 TI - [Evaluation of three concentrations of beta-blocker eyedrops. Criteria for choosing and efficacy]. AB - The problems posed by the treatment of open angle glaucoma, are long term clinical efficacy and local and general tolerance. Beta-blocking eye-drops used in monotherapy constitute a first rate treatment. The authors describe their experience with Metipranolol at three different concentrations of 0.1%, 0.3%, 0.6%. They detail the selection criteria for the best adapted concentration through the evaluation of the beneficial result. Risk ratio. PMID- 2577056 TI - Modeling the regulation of the bithorax complex in Drosophila melanogaster: the phenotypic effects of Ubx, abd-A and Abd-B heterozygotic larvae, and a homozygous Ubx- abd A hybrid gene. AB - As an intermediate step in the development of a defined quantitative model of pattern formation during Drosophila segmentation, we present here a model capable of predicting the experimentally determined levels of gene activity and their phenotypic consequences. In its present form, the model includes only four genes: the three genes of the bithorax complex (Ubx, abd-A and Abd-B) and Antennapedia. It is shown that the model is quite robust, predicting many properties in the behavior of these genes. A previously undescribed property is that all of these genes should phenotypically exhibit some kind of haploinsufficiency when present in only a single dose in the genetic background of the animal. This is shown both by the model and by a new method of quantitatively analyzing the differences in the more obvious cuticular features of the larvae, i.e., the patterns in the ventral denticle belts. The model is also capable of dealing with a complicated genetic situation, a hybrid gene of Ubx and abd-A produced by the C1 deletion. PMID- 2577055 TI - Effect of prenatal exposure to alcohol on membrane-bound enzymes during astrocyte development in vivo and in primary culture. AB - In the present work we have analyzed the effect of prenatal ethanol exposure on the activity of several glial marker and functional enzymes during the development of astrocytes isolated from rat brain as well as in primary culture. The activity of marker enzymes glutamine synthetase and butylcholinesterase showed no differences between isolated astrocytes from 15 and 70 day old control rats. However, the activity of the membrane-bound enzymes (Na+K)ATPase and 5' nucleotidase was higher in astrocytes from 70 day old control rats than in those from 15 day old animals. Although the pattern found in astrocytes from alcohol exposed rats was similar to that of controls, the levels of activity of the enzymes were lower in alcoholic than in control animals. When control astrocytes in primary culture were used, the activity of (Na+K)ATPase and 5'-nucleotidase increased throughout the entire culture period. In contrast, the maximal activity of glutamine synthetase was found at 7 days of culture. Ethanol also induced a decrease in the activity of all enzymes, which was more evident at the end of the culture period. These results indicate that the activity of the enzyme markers analyzed increased mainly during the first weeks of life and remained constant after this period. By contrast, the membrane-bound enzymes studied showed a progressive increase with age. In conclusion, since these astrocyte enzymes are important in the regulation of several neuronal functions through the control of the composition of extracellular fluid, the effect of ethanol on their activities could explain some of the neuronal alterations reported in children and animals exposed to ethanol during development. PMID- 2577053 TI - [Retinal vascular beta-adrenergic receptors in man]. AB - Beta-blockers are widely used in the primary open angle glaucoma treatment. The molecular mechanism by which these drugs reduce intraocular pressure is essentially based on the blockade of beta-adrenergic receptors localized on the ciliary processes. Vascular effects of beta-blockers, which are difficult to exhibit clinically, have been recently reported for some drugs with intrinsic sympathomimetic activity. In this study, we attempted to investigate the presence of beta-adrenergic specific binding sites on the human retinal vessels, by means of an in vitro autoradiographic technique. These receptors are localized both on arteries and veins; displacement studies indicated that they are mainly of beta-2 subtype. PMID- 2577057 TI - [Practice of pain therapy in tumor patients. What is the value of the morphine myth, placebo and the danger of addiction?]. PMID- 2577058 TI - New facts and trends in bacteriological control of mosquitoes. PMID- 2577060 TI - Some central effects of opioid antagonists. Part I. AB - This study concerned the influence of opioid antagonists: naloxone, naltrexone and diprenorphine on amphetamine hyperactivity in mice and rats, apomorphine hyperactivity in rats, amphetamine and apomorphine stereotypy in rats, and stereotyped gnawing induced by methylphenidate in mice. Naloxone, naltrexone and, in higher doses, diprenorphine attenuated the amphetamine hyperactivity in rats. In mice in the same test all antagonists at some doses produced attenuation. However they did not affect the apomorphine hyperactivity in rats. Both naloxone and naltrexone attenuated amphetamine and apomorphine stereotypy, while the effect of diprenorphine was different: it slightly attenuated the amphetamine stereotypy, but slightly potentiated the stereotypy induced by apomorphine. The influence of various antagonists on methylphenidate-induced stereotyped gnawing varied: naloxone had no effect, while naltrexone and diprenorphine showed a tendency to potentiate the response. The results suggest that naloxone and naltrexone show some actions resembling hose of antipsychotics, but of a mechanism different to that characteristic of typical neuroleptics. PMID- 2577059 TI - The development of Bacillus thuringiensis and Bacillus sphaericus as biocontrol agents: from research to industrial production. PMID- 2577061 TI - Effect of antidepressant drugs and different receptor antagonists on the grooming induced by the dopamine D-1 agonist SKF 38393. AB - The effect of four antidepressant drugs: imipramine (IMI), amitriptyline (AMI), citalopram (CIT) and mianserin (MIA), as well as various receptor antagonists: prazosin (alpha 1), yohimbine (alpha 2), ritanserin (5-HT2), atropine (Ach), chlorpyramine (H1) and SCH 23,390 (D-1) on grooming potentiated by the selective D-1 receptor agonist SKF 38,393, as well as on spontaneous grooming was studied. Antidepressant drugs inhibited in a dose-dependent manner the SKF-38,393-induced grooming, as well as spontaneous grooming in rats and mice. A similar, dose dependent inhibitory effect was shown by all the compounds mentioned above, which block various receptors. The results indicate that the inhibitory effect of antidepressants on the SKF 38,393-induced grooming is not specific. PMID- 2577062 TI - Synthesis and pharmacological properties of new derivatives of 1 diphenylacetamide-2-butanol. AB - Newly synthesized derivatives of 1-diphenylacetamide-2-butanol were investigated pharmacologically for their central properties in mice and rats. The most active were 2 compounds: racemic (RS) and enantiomer S (+) form of N-diphenylacetamide-2 butanol which produced hypothermia in normothermic mice, showed anxiolytic action in the four-plate test and reversed reserpine-induced hypothermia. PMID- 2577063 TI - Synthesis and pharmacological properties of diphenylimidazolidine acetic and propionic acids derivatives. AB - Several derivatives of diphenylimidazolidine-2,4-dione and diphenylimidazolidin-4 one acetic and propionic acids have been synthesized. Some of them were screened for their effect on the CNS in mice and rats. All the investigated compounds showed an analgesic activity. The most active one was 1-benzyl-5,5-diphenyl-3 imidazolidine-2,4-dione acetic acid. That compound exerted an inhibitory activity against the CNS, anxiety-relieving, anticonvulsant and antidepressive effects. PMID- 2577064 TI - N-aminoalkylderivatives of 1,2,3,4-tetrahydro-beta-carboline-1-spiro-4'-N'- benzylpiperidine--a putative way to novel anxiolytic agents. AB - A series of aminoalkylderivatives of 1,2,3,4-tetrahydro-beta-carboline-1-spiro-4' N'-benzylpiperidine were synthesized by means of chloroacetylation of the title compound and substitution of chlorine atom with various heterocyclic amines in DMSO, followed by LAH reduction of the carbonyl group. Of the ten tested compounds (4a-4e, 5a-5e), compound 5d given ip, but not orally, showed an anxiolytic activity in the four-plate test in mice and in the conflict test in rats. Compound 5d is devoid of an anticonvulsant or neurotoxic action. The activity of compound 5d resembles this of buspirone. PMID- 2577066 TI - Binding of pig small intestinal mucin glycopeptides to fimbriated enterotoxigenic Escherichia coli. AB - Fimbriated enterotoxigenic Escherichia coli were found to specifically bind mucin glycopeptides from pig small intestine. Bacteria with N-acetyl galactosamine specific fimbriae (F41) were found to have two populations of binding sites for mucin glycopeptides. High affinity sites (5 X 10(2) per cell) with a dissociation constant of 1 X 10(-7) M. Bacteria with sialic acid specific fimbriae (K99) were estimated to possess 3 X 10(3) binding sites per cell with a dissociation constant of 6 X 10(-7) M. PMID- 2577065 TI - Marine invertebrate mucus--agglutinating and antibacterial activity, with emphasis on Metridium senile. AB - The agglutinating and antibacterial activities of mucus from marine invertebrates are described. Mucus from eleven species was tested for the presence of haemagglutinins using a range of vertebrate erythrocytes. Mucus from Metridium senile, Ophiocomina nigra and Branchiostoma lanceolatum yielded positive results and was investigated further. The haemagglutinin of M. senile was purified, characterized and shown to be mannose-specific. Mucus from this animal was subsequently assayed for antibacterial activity using seawater isolates and verified marine and terrestrial cultures. Only two test organisms were inhibited, while the majority showed significantly enhanced growth. Possible functions of the mucus barrier in marine invertebrates are discussed. PMID- 2577068 TI - Hodgkin's disease in children: controversies and current practice. PMID- 2577069 TI - Current management and controversies. A surgeon's view. PMID- 2577070 TI - Indications for staging laparotomy and partial splenectomy. PMID- 2577067 TI - Leucoagglutinin induces differential proliferation of lymphocyte subsets. AB - In this study we have established culture conditions that allow the preferential and rapid expansion of either T cell receptor (TCR)+/CD3+16- T lymphocytes or TCR /CD3-16+ natural killer (NK) cells, or the non-selective outgrowth of both subsets. Optimal proliferation of lymphocytes was obtained using a combination of irradiated allogeneic peripheral blood lymphocytes (PBL) and irradiated Epstein Barr virus (EBV) transformed lymphoblastoid B cell lines (B-LCL). Addition of 1 microgram/ml leucoagglutinin to the culture medium induced a preferential outgrowth of TCR+/CD3+16- T lymphocytes. The proportion of TCR-/CD3-16+ NK cells was decreased to 5% or less, although still a 2000-fold multiplication of TCR /CD3-16+ NK cells was obtained at day 13. Without leucoagglutinin a 1000-fold increase of about 70% pure TCR-/CD3-16+ NK cells was obtained at day 13. Intermediate concentrations of leucoagglutinin (0.1-0.3 micrograms/ml) resulted in a non-selective expansion of both NK cells and T cells. Irrespective whether leucoagglutinin was added or not, the number of TCR+/CD3+8+ lymphocytes increased more rapidly relative to the TCR+/CD3+4+ lymphocytes resulting in an increased TCR+/CD3+8+ population size. Also under limiting dilution conditions leucoagglutinin increased the frequency of proliferating cells. In contrast to the preferential outgrowth of TCR+/CD3+8+ lymphocytes in bulk cultures, approximately 80% of the clones generated was TCR+/CD3+4+, demonstrating a growth promoting effect of TCR+/CD3+4+ lymphocytes on TCR+/CD3+8+ lymphocytes in PBL bulk cultures. PMID- 2577072 TI - Current management and controversies. A radiotherapist's view. PMID- 2577071 TI - Current management and controversies. The chemotherapist's view. PMID- 2577073 TI - Current management and controversies. The patient's view. PMID- 2577074 TI - Salvage treatment for patients with multiply relapsed Hodgkin's disease. PMID- 2577075 TI - Late effects of Hodgkin's disease treatment in children. PMID- 2577076 TI - Areas of neglect and controversy in the dental care of children with Hodgkin's disease. PMID- 2577077 TI - Hodgkin's disease in Indian children. PMID- 2577079 TI - The Pediatric Oncology Group. Studies in Hodgkin's disease. PMID- 2577078 TI - Pediatric Hodgkin's disease. Later results and toxicity--the Toronto experience. PMID- 2577080 TI - Current practice in Hodgkin's disease. The United Kingdom Children's Cancer Study Group. PMID- 2577081 TI - Results of therapy for Hodgkin's disease in childhood. The Argentine Group for Treatment of Acute Leukemia. PMID- 2577083 TI - Conclusions from Hodgkin-derived cell lines. PMID- 2577082 TI - The German cooperative therapy studies. An approach to minimize treatment modalities and invasive staging procedures. PMID- 2577086 TI - Hodgkin's disease monograph. PMID- 2577084 TI - Hodgkin's disease in children and adolescents. Experiences from the Memorial Sloan-Kettering Cancer Center, New York. PMID- 2577085 TI - Results of therapy for Hodgkin's disease at St. Jude Children's Research Hospital. PMID- 2577087 TI - Clinical overview of Hodgkin's disease. PMID- 2577089 TI - Evidence for a B-cell origin of the proliferating cells. PMID- 2577088 TI - The Sternberg-Reed cell. A cell-fusion product? PMID- 2577090 TI - The immune derangement and strategies for immunotherapy. PMID- 2577091 TI - Prognostic factors including clinical markers. PMID- 2577092 TI - Circulating cells in Hodgkin's disease. PMID- 2577093 TI - Laboratory screening: pitfalls and clinical relevance. PMID- 2577094 TI - Genetic markers and testing. PMID- 2577095 TI - Precancerous lesions. PMID- 2577096 TI - [The Edinburgh Declaration]. AB - The Edinburgh Declaration was the final document of the World Conference on Medical Education held in Edinburgh from August 7 to 12, 1988. It was intended to attain the revolutionary significance of the Flexner Report or the Declaration of Alma Ata. The social and politics aspects involved in medical education are stressed and well known educational strategies are outlined. However, the Declaration lacks internal consistency and falls short in new ideas to improve medical education. Crucial aspects of this activity are not discussed, such as the relations between medical practice and culture, between social orientation of medical students and the nature of health institutions in which they receive education. The importance of developing an ethical background in the students is also missing. Implicit in the Declaration is a charge to Medical Schools for injustices in health delivery to the population without due regard to restrictions and limitations derived from local social, political and economic conditions. In contrast to the Declaration, the background document for the Conference is an outstanding synthesis of matters with great educational significance. Specific recommendations and proposed, courses of action are clearly outlined and may be used by Medical Schools to identify problems, evaluate their current status and design policies and strategies for future development. PMID- 2577097 TI - [Pharmacokinetics and metabolic investigations of a new, atypical analeptic (GYKI 52322)]. PMID- 2577098 TI - Japanese encephalitis virus infection in mosquitoes reared from field-collected immatures and in wild-caught males. AB - Immature stages of mosquitoes collected in JE endemic areas of Karnataka, India between 1985 and 1987 were reared to adults and processed for the detection and isolation of Japanese encephalitis (JE) virus in an attempt to find naturally occurring vertical transmission of the virus. Males collected during 1985-1986 were also processed. A total of 15,785 adults reared from immatures and divided into 445 pools and 1,756 wild-collected males divided into 128 pools were processed using mosquito inoculation and immunofluorescence techniques. JE virus antigen was detected in 9 pools, 4 of which yielded JE virus. These were 2 pools of males and 1 pool of female Culex tritaeniorhynchus and 1 pool of male C. pseudovishnui, suggesting vertical transmission of JE virus in the mosquitoes. PMID- 2577099 TI - Cancer chemotherapy: concepts, clinical investigations and therapeutic advances. PMID- 2577100 TI - Phase I trials: role of the nurse investigator. AB - The role of nurses in the development, conduct, and reporting of phase I trials has in recent years become that of a clinical investigator. In collaboration with physicians and other team members, nurses are involved in every aspect of the clinical trial process and have had a favorable impact on the quality of research conducted and quality of patient care delivered. As phase I trials have achieved increasing sophistication, nursing participation at this level has become both necessary and more widely recognized. This chapter has emphasized the multifaceted and detailed responsibilities that nurses may have in phase I trials. The overall conduct and goals of phase I testing are delineated with specific nursing procedures outlined. It is of importance to recognize the contributions that skilled nurses make and the pivotal role that they play in the conduct of clinical investigation. Given the opportunity, nurses have responded to a need for their participation in clinical trials. As long as cancer continues to be a leading cause of morbidity and mortality in our society, cancer research and the development of new drug therapies will remain a priority. As the number of physicians in medical oncology approaches saturation, fewer practitioners will be trained in this subspecialty. Hence, there will be a reduction in personnel available to conduct clinical trials. With this, one may anticipate a growing need for nurses skilled in drug development and cancer treatment trials. PMID- 2577101 TI - The role of chemotherapy in the treatment of squamous cell tumors of the esophagus. PMID- 2577102 TI - Systemic chemotherapy of transitional cell carcinoma of the urothelium. PMID- 2577103 TI - Nasopharyngeal cancer, undifferentiated type: the medical oncologist's viewpoint. PMID- 2577106 TI - Alkylating agents: mechanisms and modulation. PMID- 2577104 TI - Primary central nervous system lymphomas. PMID- 2577107 TI - Laboratory aspects of multidrug resistance. PMID- 2577105 TI - Reduced folates and fluoropyrimidine antitumor efficacy. PMID- 2577108 TI - Multidrug resistance: clinical findings and implications. PMID- 2577109 TI - Current status of trimetrexate, a folate antagonist with antineoplastic and antiprotozoal properties. PMID- 2577110 TI - Daunomycin and doxorubicin Lym-1-drug conjugates for the treatment of malignant lymphomas. PMID- 2577111 TI - Disease-modifying antirheumatic drugs: gold, penicillamine, antimalarials, and sulfasalazine. PMID- 2577112 TI - Clinical trials referral resource. Adjuvant treatment of colon cancer. PMID- 2577113 TI - TNF-alpha gene polymorphisms: association with type I (insulin-dependent) diabetes mellitus. AB - The localization of TNF genes on the short arm of chromosome 6 between HLA B and the complement genes focused attention to that genetic region which harbors many immunologically relevant genes and is also thought to hold susceptibility genes for a variety of autoimmune diseases that are linked to specific alleles of particular loci in the HLA D region. Since the recently established HLA-DR-DQ variation accounts only for part of the genetic susceptibility to insulin dependent diabetes mellitus (IDDM) we searched for genomic variation of the tumour necrosis factor (TNF) alpha. We have identified a TNF-alpha restriction fragment length polymorphism (RFLP) with NcoI and analysed diabetic patients including their families, controls and homozygous typing cell lines (HTC) defined by the 10th International Histocompatibility Workshop. Segregation analysis in families and HTC results show a strong linkage of the TNF-alpha 5.5 kb allele with DR types in particular with A1B8DR3. This tight linkage of TNF-alpha alleles with extended haplotypes and the significant increase of heterozygotes in patients could lead to some explanation of the DR3 association with a variety of autoimmune diseases particularly IDDM. PMID- 2577114 TI - IL-6 gene polymorphism in rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, systemic lupus erythematosus, and in healthy Danes. AB - The restriction enzymes MspI and BglII identify two different two-allele restriction fragment length polymorphisms (RFLP) in the human IL-6 genes of healthy Danes. Co-dominant segregation was demonstrated for both marker-systems and the test for Hardy-Weinberg equilibrium showed no significant deviation from expectations. There is a strong correlation between the two marker systems. The two IL-6 RFLP's were studied in Danish patients with rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, and systemic lupus erythematosus. The frequencies of the MspI and BglII marker phenotypes did not differ between healthy controls and the three disease groups. No extra or missing DNA fragments were observed in the disease groups when compared with controls. PMID- 2577116 TI - Short-term effects of temazepam in the EEGs of healthy volunteers. AB - In this study effects of temazepam on the EEGs of 10 healthy volunteers were detected using a standardized EEG registration procedure applied in a controlled environment. The EEGs were recorded both before and after administration of 20 mg temazepam as well as before and after placebo. A mean power spectrum was computed for each EEG from the 'eyes closed' condition, and the Student t test was used to detect differences in the spectra of the pre- and posttreatment EEGs in both placebo and drug conditions. For all 10 subjects the drug condition was easily distinguishable from the placebo condition based on the results of the t test. PMID- 2577115 TI - Increased activated T-lymphocytes and normal thyrotropin receptor antibody levels in Graves' disease in long-term remission. AB - The involvement of the immune system in the attainment and maintenance of carbimazole-induced remission in Graves' disease is poorly understood. We have investigated levels of T-lymphocytes expressing the HLA DR marker of activation and levels of thyrotropin receptor antibody (TRAb) in patients in sustained, carbimazole-induced, long-term remission from Graves' disease (median duration of remission 29 months, range 7-64). Levels of activated T-lymphocytes were increased in patients with long-term remission compared with controls (p less than 0.05) and were no different from the high levels found in patients with active Graves' disease. In contrast, levels of TRAb were normal in patients in long-term remission but high in patients with active disease (p less than 0.01). These results show that increased activated T-lymphocytes but normal levels of antibody to the thyrotropin receptor characterize patients in carbimazole-induced long-term remission of Graves' disease suggesting that activated T-lymphocytes may be important in the maintenance of remission. PMID- 2577117 TI - Rapid tranquilization: a reevaluation. AB - Years of experience have indicated that the widespread and frequent use of rapid tranquilization is not based on demonstrated efficacy. Multiple high-dose administration of neuroleptics parenterally does not produce rapid relief of psychosis and, at the same time, exposes the patient to risk of severe side effects. Rapid tranquilization may only have a limited and specific applicability; therefore, it is important to reexamine its clinical indications and to search for safer alternatives. PMID- 2577118 TI - In situ hybridization of peptide mRNAs on vibratome sections. AB - In situ hybridization procedures that have been used successfully for the localization of somatostatin and cholecystokinin mRNAs in neurons on cryostat sections of rat brain, were tested for applicability to vibratome sections of rat and guinea pig brain. Somatostatin and cholecystokinin mRNAs were localized to neurons in 30 microns thick vibratome sections of brain from both species by use of 32P labelled oligodeoxyribonucleotide (oligomer) probes. Somatostatin mRNAs was localized to neurons in the periventricular region of the preoptic area of rat, and guinea pig brain. Cholecystokinin mRNAs were localized to neurons of rat hippocampus. Hybridization signal, background and resolution achieved with vibratome sections were comparable to those obtained with the more commonly used cryostate sections. PMID- 2577119 TI - [The immunological basis of vaccination against carious disease. Microorganism interactions. Specific host defense system. Immunological protection of the oral cavity]. AB - The authors describe the very complex interactions of the microorganisms of the oral cavity and among these latter and the guest organism. There are described the mechanisms of aspecific defense of the oral cavity and give some outlines of the anatomy and of the physiology of the organs and of the glandular structures of the specific immune defence of the oral cavity through blood and saliva. PMID- 2577120 TI - Adenosine A1 receptors inhibit both adenylate cyclase activity and TRH-activated Ca2+ channels by a pertussis toxin-sensitive mechanism in GH3 cells. AB - The present study has examined the effects of adenosine A1 receptors on second messenger processes in GH3 cells. A1 receptors are present which are shown to inhibit adenylate cyclase in a GTP-requiring manner. Hormone (VIP) stimulation is also absolutely required for the observation of inhibition. Adenosine A1 receptor analogues also inhibit TRH-stimulated [Ca2+]i-mobilization in GH3 cells. Both effects of the adenosine receptor agonists are apparently mediated by pertussis toxin substrates, of which there are two--41,000 and 40,000 daltons respectively- in these cells. Somatostatin exerts analogous effects to the adenosine agonists in GH3 cells. Thus it may turn out that a general property of 'cyclase inhibitory receptors' is also to inhibit [Ca2+]i-mobilization in the same cells, when such mechanisms are present. PMID- 2577121 TI - Phospholipid metabolism and T cell activation: receptor triggering is associated with the inhibition of phosphatidylserine synthesis. AB - Activation of Jurkat T lymphocytes to produce IL2 is accompanied by a strong inhibition of phosphatidylserine (PS) synthesis. This inhibition was obtained either with the mitogenic lectin PHA, anti-CD3 monoclonal antibodies (mAb), anti CD2 mAb or anti-Ti mAb. Bypassing membrane receptor signalling, by using a Ca2+ ionophore or a protein phosphatase inhibitor, sodium ortho-vanadate, also results in a marked inhibition of PS synthesis. Activators of phospholipid -Ca2+ dependent protein kinase C (PKC) did not significantly modify PS synthesis, suggesting that the observed changes only involve the transduction of the first activation signal. PS being a necessary cofactor for PKC, our results strongly suggest that the inhibition of PS synthesis induced by receptor triggering exerts a feed back control on PKC therefore leading to a transient activation of the enzyme upon full lymphocyte activation. PMID- 2577122 TI - Intraepithelial lymphocytes contain virus-specific, MHC-restricted cytotoxic cell precursors after gut mucosal immunization with reovirus serotype 1/Lang. AB - Reovirus 1 has been intraduodenally administered to mice to determine whether virus-specific cytotoxic cells can be elicited within the intestinal epithelium. We have found that reovirus-stimulated, but not control mice, generate virus specific cytotoxic effector cells when isolated intraepithelial lymphocytes are restimulated in vitro. These effector cells are restricted by major histocompatibility complex (MHC) class I determinants and thus appear to utilize the T cell antigen receptor and to be of the T cell lineage. These results raise the possibility that cytotoxic T lymphocytes (CTL) may be an important component of the host immune response in the intestinal epithelium. PMID- 2577123 TI - Type II collagen-induced murine arthritis. II. Genetic control of arthritis induction is expressed on L3T4+ T cells required for humoral as well as cell mediated immune responses to type II collagen. AB - The present study investigates the cellular and molecular mechanisms responsible for expressing genetic control of type II collagen-induced murine chronic arthritis. Analyses were made for both humoral and cellular immune responses, since the induction of arthritis required synergy between both types of immunities. Immunization of high (DBA/1) and low (C57BL/6, C3H/He, BALB/c) responder mice with native bovine type II collagen resulted in the production of the respective high and low levels of anti-collagen antibody. However, polyclonal in vitro stimulation of normal spleen cells from high or low responder mice with lipopolysaccharide (LPS) induced a comparable magnitude of anti-collagen antibody responses, indicating the localization of the genetic defect at cellular levels other than B cells themselves. In contrast to immunization with native collagen, sensitization of DBA/1 mice with heat-denatured collagen failed to stimulate B cells, but resulted in selective generation of L3T4+ T cell-mediated immunity. These included anti-collagen delayed-type-hypersensitivity (DTH) responses and the generation of various interleukins (IL) responsible for antibody production as well as DTH responses. It was demonstrated that there was appreciable difference in the magnitudes of these responses between lymphoid cells from high and low responder mice. Differential effects of sensitization with heat-denatured collagen in high versus low responders were reflected on the genetic difference in the development of chronic arthritis. A typical arthritis was induced neither in denatured collagen-sensitized DBA/1 mice nor in unsensitized mice transferred with anti-collagen antiserum. However, the antiserum transfer into denatured collagen-sensitized DBA/1 mice induced chronic perpetuating arthritis. This sharply contrasted with the failure of the same aliquot of the antiserum to induce a chronic arthritis when inoculated into denatured collagen-sensitized low responder mice. These results indicate that the genetic control of the induction of arthritis is expressed on L3T4+ T cells which are required for generating anti collagen humoral as well as cell-mediated immunities as assessed by DTH responses in vivo or lymphokine productions in vitro. PMID- 2577125 TI - The development of the International Classification of Impairments, Disabilities, and Handicaps in France. AB - Until recently there has been little satisfactory information about people with disabilities in France, partly due to reluctance by those framing legislation to formulate a definition of handicap. A preliminary translation of the ICIDH in 1981 stimulated interest in the problem, and the National Technical Centre on Handicaps issued a definitive translation in 1988. The word 'handicap' caused difficulties in French as it approximates to the global term disablement. This report describes how the difficulties were surmounted, and how the National Technical Centre then proceeded to undertake activities to extend awareness of the ICIDH. The impact of the classification is reviewed, and applications in social administration, rehabilitation and geriatrics, epidemiological surveys, and education and training are discussed. In 1989 the National Centre was appointed as a WHO collaborating centre for the ICIDH, and future aims are described. PMID- 2577124 TI - Paradoxical effects of isothiocyanate analog of tolazoline on rat aorta and human platelets. AB - The isothiocyanate analog (IBI) of tolazoline produced contraction of the rat aortic strip, with an ED50 value of 1.63 x 10(-5) M. The maximum contraction of the analog was nearly equal to that of tolazoline or phenylephrine. At 27 degrees C the tissue reactivity of phenylephrine and IBI was similar. When compared at equiactive concentrations, the total duration of contraction of IBI was three times longer than that of tolazoline. Thus, the longer duration of action of IBI may be attributed to the S=C=N group substitution of the molecule. IBI at 10(-6) M shifted the dose-response curve of phenylephrine to the right with reduction in maxima. Phentolamine and other alpha 1 or alpha 2 adrenoceptor blockers failed to block the responses of IBI in aorta, whereas verapamil or nifedipine blocked the response significantly. It appears that IBI is acting through calcium-channel sensitive or calcium-receptor-related mechanism(s). In aspirin-treated platelets from human plasma, a distinct phase of aggregation induced by epinephrine can be blocked by IBI with KB of 2 x 10(-5) M. This indicates a small but selective alpha 2 related action of IBI. The aggregation induced by ADP or second component of aggregation induced by epinephrine were also blocked by IBI at concentrations comparable to that of the alpha 2-adrenoceptor-mediated response. This indicates a lack of specificity of IBI in differentiating various phases of aggregation. Therefore, as compared to tolazoline, IBI presents an interesting paradox in its interaction with various receptors or mechanisms in the vascular tissue and platelets. PMID- 2577126 TI - Multiple receptor regulation of cyclic nucleotides in rat pinealocytes. PMID- 2577127 TI - Mechanisms subserving brain water-electrolyte homeostasis. PMID- 2577128 TI - NMDA receptor antagonists disrupt the retinotectal topographic map. AB - We tested the effect of two NMDA receptor antagonists, APV or MK801 (with NMDA), and the receptor agonist NMDA on the maintenance of retinal topography in frogs. Topography was assayed by measuring the dispersion of retrogradely labeled ganglion cells following a local HRP injection into the tectum. In untreated tadpoles, labeled cells covered about 5% of the retinal area. In APV- or MK801/NMDA-treated tadpoles, labeled ganglion cells covered 17% and 10% of the retinal area, respectively. Neither treatment with L-APV nor with NMDA disrupts the fidelity of the retinotectal projection. Neither APV- nor NMDA-treated ganglion cell terminals differed from untreated terminals with respect to tangential area, branch number, or branch density. These data support a role for the NDMA receptor in visual system development. PMID- 2577129 TI - Long-term potentiation of hippocampal mossy fiber synapses is blocked by postsynaptic injection of calcium chelators. AB - The role of intracellular calcium in an APV-insensitive form of long-term potentiation (LTP) has been studied at the hippocampal mossy fiber synapse. Intracellular calcium was buffered by iontophoretic injection of either BAPTA or QUIN-2, into CA3 pyramidal neurons. The slow calcium-dependent after hyperpolarization was used as an indicator of buffering. LTP was elicited in control and in APV-treated cells (6/6 and 4/5 cell, respectively). In contrast, LTP was observed in only 2/9 BAPTA-loaded cells and in 1/4 QUIN-2-loaded cells. The magnitude of LTP for control and APV-treated cells were not significantly different, but both groups showed significantly greater LTP than BAPTA-loaded cells. These results suggest that an increase in postsynaptic calcium is required for the induction of mossy fiber LTP. PMID- 2577130 TI - Synaptic vesicles immunoisolated from rat cerebral cortex contain high levels of glutamate. AB - L-Glutamate is regarded as the major excitatory neurotransmitter in the mammalian CNS. However, whether the released transmitter originates from a cytosolic pool or is discharged from synaptic vesicles by exocytosis (vesicle hypothesis) remains controversial. A problem with the general acceptance of the vesicle hypothesis is that the enrichment of glutamate in synaptic vesicles has not been convincingly demonstrated. In the present study, we have analyzed the glutamate content of synaptic vesicles isolated from rat cerebral cortex by a novel immunobead procedure. A large amount of glutamate was present in these vesicles when a proton electrochemical gradient was maintained across the vesicle membrane during isolation. Compared with the starting fraction, glutamate was enriched more than 10-fold relative to other amino acids. Addition of N-ethylmaleimide prevented glutamate loss during isolation. Isotope exchange experiments revealed that exchange or re-uptake of glutamate after homogenization is negligible. We conclude that rat brain synaptic vesicles contain high levels of glutamate in situ. PMID- 2577131 TI - Drug resistance: the clinical problem. PMID- 2577132 TI - Drug resistance in cancer therapy. PMID- 2577133 TI - Phosphoprotein, protein kinase C, and second-messenger system changes in human multidrug-resistant cancer cells. PMID- 2577134 TI - Alkylating agent resistance. PMID- 2577135 TI - Mathematical models of drug resistance and chemotherapy effects. PMID- 2577136 TI - Mechanisms of resistance to cisplatin and alkylating agents. PMID- 2577137 TI - Glutathione S-transferase and drug resistance. AB - GST isozymes are an important part of the normal cellular defense against toxic xenobiotics and carcinogens. These multifunctional proteins can interact with a broad range of substrates in a variety of ways. In particular, GSTs have been implicated in the detoxication of many antineoplastic agents. Elevated levels of certain GST isozymes have been associated with malignant transformation and with experimental drug resistance. Although the role of GST in antineoplastic drug resistance is unclear, recent studies have shown increased activity of GST in many human tumors relative to normal tissues. These findings raise the possibility that the presence of certain GST isozymes may be a marker for malignant transformation in some human tumors, and that GSTs may play a role in de novo and acquired drug resistance. Identifying the factors which regulate the expression of these drug-metabolizing enzymes as well as agents which inhibit their activities may provide new insights into the therapy of tumors clinically refractory to chemotherapy. PMID- 2577139 TI - Multidrug resistance in human tumors. PMID- 2577138 TI - Tumor cell drug and radiation resistance: does an interrelationship exist? PMID- 2577140 TI - Structure and function of P-glycoprotein. AB - P-glycoprotein remains the best understood molecule that has been implicated in the multidrug resistance phenomenon. As I have attempted to show, our understanding of this molecule is still in its infancy, with many questions as yet unanswered. It is anticipated that the answers to these questions will contribute to our understanding of drug resistance, as it relates to cancer, and also to our understanding of what appears to be a fundamental transport system. PMID- 2577141 TI - Anthracycline resistance. PMID- 2577142 TI - Circumvention of drug resistance with calcium channel blockers and monoclonal antibodies. PMID- 2577143 TI - P-glycoprotein in breast cancer. PMID- 2577144 TI - The interaction of the enantiomers of carvedilol with alpha 1- and beta 1 adrenoceptors. AB - The stereoselectivity of carvedilol, a novel beta-adrenoceptor antagonist and vasodilator with one asymmetric carbon atom, was examined at alpha 1- and beta 1 adrenoceptors in vitro and in vivo. (-)-(S)-Carvedilol is a potent, competitive antagonist of the beta 1-adrenoceptor-mediated positive chronotropic response to isoproterenol in guinea pig atrium, with a dissociation constant (KB) of 0.4 nM. (+)-(R)-Carvedilol was more than 100-fold less potent than the (-)-S-enantiomer as an antagonist of beta 1-andrenoceptors, having a KB of approximately 45 nM. Consistent with these findings (-)-(S)-carvedilol (0.1 mg/kg, i.v.) produced a 25 fold rightward shift in the beta 1-adrenoceptor-mediated positive chronotropic response to isoproterenol in pithed rats, whereas the (+)-R-enantiomer had no beta 1-adrenoceptor blocking activity in vivo at this dose. In contrast to the marked degree of stereoselectivity observed at beta 1-adrenoceptors, both (-)-(S) and (+)-(R)-carvedilol produced equal antagonism of the alpha 1-adrenoceptor mediated vasoconstrictor response to norepinephrine in rabbit aorta, with KB values of 14 and 16 nM, respectively. Furthermore, in the pithed rat, the alpha 1 adrenoceptor-mediated pressor dose-response curve to cirazoline was shifted approximately 6-fold to the right by both the (+)-R- and (-)-S-enantiomers of carvedilol at a dose of 1 mg/kg, i.v. In anesthetized spontaneously hypertensive rats, (-)-(S)-carvedilol was 6-fold more potent as an antihypertensive than (+) (R)-carvedilol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2577145 TI - Are boys with the syndrome of agenesis of the anterior abdominal wall muscles always infertile when they grow up? PMID- 2577147 TI - P-fimbriae vaccines. II. Cross reactive protection against pyelonephritis. AB - Protection against acute pyelonephritis was induced by immunization of baboons with purified P-fimbriae of Escherichia coli as vaccines. To test for cross protective capacity of two different P-fimbriae vaccines we vaccinated baboons with P-fimbriae purified from either E. coli strain ER2 or strain JR1 and subsequently challenged the animals with E. coli strain JR1. All vaccinated animals showed elevated antibody titers to P-fimbriae from both of the E. coli strains used. Both vaccines tended to reduce the time of bacteriuria. They partially prevented pyelonephritis and protected against loss of renal function. PMID- 2577146 TI - P-fimbriae vaccines. I. Cross reactive antibodies to heterologous P-fimbriae. AB - To test for cross-protective capacity of two different P-fimbriae vaccines we vaccinated baboons with fimbriae purified from either Escherichia coli strain ER2 or strain JR1. The vaccinated animals showed elevated antibody titers to P fimbriae from each of the E. coli strains used, suggesting cross-reactivity as was expected from the results of immunoprecipitation of the fimbriae. Enzyme linked immunosorbent assay inhibition by heterologous P-fimbriae proved this to be true immunologic cross-reactivity. PMID- 2577148 TI - Study of lymphocyte populations and natural killer activity in severe aplastic anaemia. AB - Thirty-one patients (pts) with aplastic anaemia (AA) were studied whose probable etiology were: idiopathic (16 pts), nocturnal aroxysmal haemoglobinuria (NPH) (2 pts), benzene (4 pts), agrotoxics (5 pts), pharmaceutical drugs (2 pts) and insecticides (2 pts). A decrease in total lymphocyte counts was seen in 10 pts belonging mainly to the NPH and pharmaceutical drug groups, whereas, in the benzene group the opposite was found. B cell levels were low in 9 out of 20 pts. T cell levels varied, the majority of patients had normal levels, 13 presented low levels and 4 had increased numbers. CD4 levels were low in 14 pts and T cell numbers were compensated in some by an increase in CD8 cells. Our results show that there is a great heterogeneity among the patients and there might be differences in the immunological profile of aplastic anaemia depending on the causative agent of the disease. PMID- 2577150 TI - H2-antagonists: synthesis and activity of 2-amino-5-thiazolyl derivatives. AB - 2-Amino- and 2-guanidinothiazole derivatives having in position 5 a methylthioalkyl side-chain with urea-equivalent moieties were prepared for comparison with H2-antagonists of cimetidine and tiotidine series. Examination of the pharmacological results obtained from experiments on guinea pig atria and in cat gastric fistula, suggests some general observations about the structure activity relationship of the compounds synthesized. The activity trend of these products is different from that of H2-imidazole antagonists while it is similar to that of the tiotidine series. Unlike the tiotidine similar compounds, the 2 guanidino-5-thiazolyl derivatives are less potent than the corresponding 2-amino 5-thiazolyl products. The activity of the latter ones is reduced in comparison to that of tiotidine or cimetidine. PMID- 2577149 TI - A search for common immunological abnormalities at the onset of murine lupus in two genetically different strains. AB - Mice of the genetically different BXSB and MRL/lpr strains develop murine lupus spontaneously at about three months of age. Polyclonal B-cell activation is thought to play a major role in the development of the syndrome in each strains, but the immunological events which lead to this activation are not known. We therefore examined the immune characteristics of mice aged 10-16 weeks, at the onset of the disease. We found consistent abnormalities in the percentages of lymphocyte sub-populations in both male BXSB, and male and female MRL/lpr mice. In particular, the ratio of helper to suppressor/cytotoxic T cells was found to be significantly lower in male BXSB, and in male and female MRL/lpr mice than in normal, control, DBA2 mice. Significant increases in serum IgG and IgA concentrations, indicative of polyclonal B cell activation, were present in each strain. The histological appearance of the lymphoid organs and the functional responses to mitogen stimulation were, however, distinctly different. We conclude that defective immunoregulation is likely to be significant in the initiation of murine lupus, since it is detectable at the onset of disease in two genetically distinct strains. It may be associated, however, with different immunological phenomena in strains of different genetic backgrounds. PMID- 2577152 TI - [Drug therapy of pheochromocytoma]. AB - The Authors briefly review the clinical findings, the diagnostic biochemical procedures and the management of pheochromocytoma. The most recent pharmacological approaches with calcium-channel blockers or angiotensin converting enzyme inhibitors are particularly discussed. PMID- 2577151 TI - Synthesis of the new alpha- and beta-adrenergic antagonist 1-[1-(2 benzodioxanylmethyl)-4-piperidyl]amino-3-(1-naphthoxy)-2- propanol. AB - The synthesis and in vitro alpha- and beta-adrenergic blocking potency of 1-[1-(2 benzodiaxanylmethyl)-4-piperidyl]amino-3-(1-naphthoxy-2-pr opanol (I) are described. Thus, N-benzyl-4piperidone was protected and debenzylated to the carbamate (V), which upon alkaline hydrolysis and acylation gave benzodioxanic amide (IX). Reduction of the amide group, deprotection of the ketone function of (X), and reductive amination gave the 4-aminopiperidine (XIII), which was finally condensed with the appropriate epoxide to yield the aminopropanol (I). Compound (I) is formally derived from a combination of piperoxan (II) and propranolol (III), and was approximately 10 times less potent than each one of these drugs, as an alpha- and beta-adrenergic blocker respectively. PMID- 2577155 TI - Treatment of soft tissue sarcomas. PMID- 2577153 TI - Human multidrug resistant KB cells overexpress protein kinase C: involvement in drug resistance. AB - Among the many phenotypic characteristics of multidrug resistance (MDR), the presence of P-glycoprotein is nearly always observed, and it appears that the plasma membrane of the multidrug resistant cell is integrally involved in controlling drug resistance. Another membrane-associated protein kinase, protein kinase C (PKC), has been shown to regulate the flow of information to the cell interior and to control the efflux of a number of different compounds. We therefore initiated a study of PKC and MDR. We found that multidrug resistant sublines from both mouse sarcoma 180 and human KB lines exhibited 80-90% increases in basal PKC activity. The mechanism of the increase appears to be quite different in the two cell lines. The human KB cells overexpress the alpha isozyme of PKC, commensurate with the increase in alpha-PKC protein, whereas the mouse cells do not overexpress alpha-mRNA but increase alpha-PKC protein. Furthermore, it appears that PKC activity plays a functional role in drug resistance, since inhibition of endogenous PKC activity by staurosporine resulted in decreased resistance to Adriamycin. We also found that phosphorylation of MDR cell membrane vesicles by purified PKC, followed by immunoprecipitation of P glycoprotein with monoclonal antibody C219, resulted in a level of phosphorylation of P-glycoprotein that was greater than the endogenous phosphorylation level. The data presented indicate that MDR cells of diverse species exhibited enhanced PKC activity but that the mechanisms were different. The increased kinase activity may have biological relevance to MDR since PKC appears to be coupled to P-glycoprotein function. PMID- 2577154 TI - Modulation of multidrug resistance in Chinese hamster cells by liposome encapsulated doxorubicin. AB - A Chinese hamster cell line (LZ), selected for multidrug resistance (MDR), exhibits a 3,000-fold resistance to doxorubicin, compared to parental V-79 cells. These drug resistant cells have amplified MDR genes, overexpress P-glycoprotein, and in the presence of doxorubicin show reduced intracellular drug accumulation. Using liposome-encapsulated doxorubicin (Rahman et al. Cancer Res. 45:796-803; 1985), we observed partial reversal of the resistance of LZ cells to this drug and a higher intracellular drug accumulation, compared to free drug. Parental V 79 cells, however, did not exhibit differences in survival or in drug accumulation when treated with encapsulated or free doxorubicin. Comparison of the effect of liposome-encapsulated doxorubicin with that of verapamil in reversing drug resistance showed that the liposomal preparation was as effective as verapamil used at its maximum clinically relevant concentration (1.5 microM). These results suggest that the use of liposomes as carriers of anticancer drugs may offer a strategy for overcoming MDR in tumor cells. PMID- 2577156 TI - Pathology of soft tissue sarcomas. PMID- 2577157 TI - Preoperative intra-arterial chemotherapy. AB - The major factors affecting prognosis of patients with soft tissue sarcomas are local control, size of the primary tumor, and the grade of the tumor. The only factor that can be influenced following appropriate diagnostic procedures is local control. Surgery alone, even radical surgery or amputation, is insufficient to control large, poorly differentiated tumors in many cases. Preoperative therapy has been shown to be a highly effective method for local disease control. Intra-arterial therapy appears to have several advantages in the treatment of extremity sarcomas. (1) Intra-arterial therapy results in at least a sixfold increase in the concentration of drug in the blood perfusing the tumor. If combined with proximal occlusion of blood flow (balloon occlusion or tourniquet occlusion), the concentration of drug being delivered to the tumor may increase by 30-fold [32]. This high local concentration of chemotherapy is achieved in most cases without the high systemic toxicity that would be required by intravenous therapy. (2) Chemotherapy infusion prior to surgery allows administration of cytotoxic therapy through an undisturbed blood supply. This allows for an improved effect of therapy at the tumor margin, which is the area at risk for seeding the wound at the time of extirpative surgery. This may facilitate limb salvage in patients with bulky tumors. (3) Responses to this preoperative therapy allows an in vivo evaluation of the efficacy of the drug against the individual tumor. This may aid in determining efficacy of using the drug for postoperative adjuvant therapy. (4) Preoperative therapy allows treatment of the tumor while awaiting construction of custom prostheses, especially in patients with osteosarcomas of the extremities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2577159 TI - Treatment of soft tissue sarcomas. Diagnostic imaging. PMID- 2577160 TI - Musculoskeletal tumor staging: 1988 update. PMID- 2577158 TI - Thermochemotherapy for soft tissue sarcoma. PMID- 2577161 TI - Surgery of soft tissue sarcomas. PMID- 2577162 TI - The role for radiation therapy in the management of patients with sarcoma of soft tissue in 1988. PMID- 2577163 TI - Chemotherapy in advanced soft tissue sarcomas. PMID- 2577164 TI - Adjuvant chemotherapy for soft tissue sarcomas. PMID- 2577166 TI - Basic and clinical concepts of lung cancer. PMID- 2577165 TI - Lung cancer in developed and developing countries. PMID- 2577167 TI - Autocrine growth factors and lung cancer. PMID- 2577169 TI - Clinical correlation of tumor endocrine markers in lung cancer. PMID- 2577170 TI - The impact of prophylactic methods in the control of lung cancer in the U.S.A. PMID- 2577168 TI - Cytogenetic abnormalities in lung cancer. PMID- 2577172 TI - Current staging of lung cancer: an overview of current and newer approaches. AB - The purpose of this chapter is to update some of the current approaches to the pretreatment assessment of patients with lung cancer. We will place emphasis on both standard staging and newer techniques. Because of their clinical relevancy, small-cell (SCLC) and non-small-cell (NSCLC) lung cancers have been divided to emphasize the special needs and approaches to each. PMID- 2577171 TI - Can human small-cell lung cancer cell lines be applied for optimizing chemotherapy? PMID- 2577173 TI - Prognostic factors in adenocarcinoma of the lung. PMID- 2577174 TI - Surgical adjuvant therapy of non-small-cell lung cancer. PMID- 2577175 TI - High-dose chemotherapy of small-cell lung cancer with and without bone marrow transplantation. PMID- 2577176 TI - CNS therapy in small-cell lung cancer. PMID- 2577177 TI - Late complications associated with the treatment of small-cell lung cancer. PMID- 2577178 TI - Psychosocial aspects of patients with lung cancer in controlled clinical trials. PMID- 2577179 TI - Advances in the diagnosis of lung tumors. PMID- 2577181 TI - Immunohistochemistry of lung cancer: cell differentiation and growth properties. PMID- 2577180 TI - Observer variability studies of the WHO classification of lung cancer. PMID- 2577182 TI - Oncogenes and human lung cancer. PMID- 2577184 TI - Urologic oncology. PMID- 2577183 TI - Prostatic ultrasound for the early detection of prostate cancer. PMID- 2577185 TI - Laser treatment of transitional cell cancer of the bladder and upper urinary tract. AB - Nd:YAG laser therapy now has a well-defined role in the treatment of superficial bladder cancer, that is, it is indicated only when one needs to destroy present tumors. Available results suggest that tumor recurrence is reduced, but definitive evidence of this is lacking. The laser's main advantage is that the procedure is carried out without anesthesia on an outpatient basis, because it is a noncontact technique that is associated with minimal morbidity and reduced pain and bleeding. Nd:YAG laser use in invasive bladder cancer would appear to be adequate for palliation only. For this indication, its benefits must be compared with conventional palliative TUR and/or radiation therapy. Laser therapy of tumors in the upper urinary tract is still in its infancy. Urothelial cancer is a multifocal disease, and the critical caveat, as in the case of bladder cancer, is tumor recurrence. Routine access to the upper tract and accurate assessment of the grade and stage of the tumor and the multifocality of the disease are of paramount importance and are not yet perfected. Photodynamic therapy is an intriguing modality. It has much potential for future development, but at present, because of its reduced ability to control superficial cancer, particularly when compared with other available forms of treatment such as intravesical BCG, and because of its significant associated morbidity, its use remains investigational. PMID- 2577186 TI - Systemic chemotherapy in the management of bladder cancer. AB - The treatment of bladder cancer is in a state of evolution. With the advent of effective chemotherapy, multimodal treatment planning is needed to ensure the best results. This requires the participation of the urologist, medical oncologist, radiologist, and radiation therapist in order to determine the optimal treatment strategy for each patient. Currently, radical cystectomy should be considered standard therapy. Neoadjuvant or true adjuvant chemotherapy are still investigational. Randomized trials should be designed to define those patients who will benefit from combined modality therapy, the sequence in which it should proceed, and its impact on disease-free and total survival. Certain principles in patient management require emphasis. 1. The patient must be carefully staged prior to treatment and later restaged thoroughly; whenever possible pathologic confirmation is recommended. Following chemotherapy, all sites of measurable and evaluable disease should be reassessed. Patients with residual masses may have only fibrosis, or microscopic tumor, and complete resection may result in prolonged disease-free survival. 2. Cystectomy after chemotherapy appears to be indicated when this is the only site of disease. If a patient responds systemically with a CR, but has residual disease in the bladder, salvage cystectomy may translate into a prolonged survival. Similarly, a patient who relapses in the bladder following chemotherapy should have surgery. It is unclear if patients with initially unresectable disease who are downstaged (PR) to a resectable lesion should undergo surgery or be consolidated with radiation therapy. 3. Adequate renal function is needed to give optimal doses of chemotherapy. Patients with ureteral obstruction often benefit from a nephrostomy tube. The creatinine clearance may improve following urinary diversion to allow full-dose chemotherapy. PMID- 2577187 TI - The role of radical prostatectomy in the treatment of cancer of the prostate. PMID- 2577188 TI - Mesenchymal-epithelial interactions in the growth and development of the prostate. PMID- 2577189 TI - Biological basis for chemohormonal therapy for prostatic cancer. PMID- 2577190 TI - Mechanisms of action of intravesical bacillus Calmette-Guerin for bladder cancer. AB - Though superficial bladder-cancer patients have been treated with intravesical BCG since 1976, the mechanisms of action remain unknown. Evidence points towards an immune mechanism of BCG-induced antitumor activity. Although specific antitumor immunity may play a role in BCG immunotherapy, additional work is needed to more clearly define this possibility. Several investigators have noted a clinical association between favorable response to BCG therapy and a systemic response (DTH) to BCG antigen, indicated by conversion to a positive purified protein derivative (PPD) skin test. Additional animal studies have, in turn, documented evidence of specific binding between BCG and fibronectin found in the urothelial basement membrane, which appears necessary for the development of both the DTH response and antitumor activity. Other studies have suggested which cellular components of the immune system and lymphokines may be involved in the antitumor response. Further work will be needed to better understand BCG mechanisms, as these findings may be important to other forms of cancer therapy. Questions of immune suppression, genetic influence on the immune response, and immunocompetence at the time of surgery may assume increasing importance. A strong effort will therefore be needed to better understand these mechanisms so that patients may be selected, treated, and followed in a more effective manner. PMID- 2577191 TI - Adoptive immunotherapy of urologic tumors. PMID- 2577192 TI - Modified retroperitoneal lymphadenectomy for patients with clinical stage I testicular cancer. PMID- 2577193 TI - Penile carcinoma: the case for primary lymphadenectomy. AB - In the preceding sections, the authors have presented an approach to the management of patients with squamous-cell carcinoma of the penis selected to maximize the therapeutic benefits in high-risk patients while minimizing morbidity in low-risk patients. A clinical staging system is presented in order to approach this problem in a logical fashion. Patients with stage I penile carcinomas are all managed by eradication of the primary lesion followed by expectant management of the inguinal lymph nodes. Persistent inguinal adenopathy after treatment of the primary lesion has been a very rare occurrence in this group of patients in our experience. Patients with stage II penile carcinoma are managed by eradication of the primary lesion, 6-8 weeks of antibiotic therapy, and inguinal lymphadenectomy. The available literature suggests a high incidence of inguinal lymphatic metastases in this group of patients and supports the need for early lymphadenectomy. Finally, patients with clinical stage III disease, i.e., persistent adenopathy after eradication of the primary lesion and 6-8 weeks of antibiotic therapy, all undergo inguinal lymphadenectomy. This group is at extremely high risk and does poorly without aggressive surgical management. PMID- 2577194 TI - Recent advances and controversies in the management of Wilms' tumor. PMID- 2577195 TI - Alternative forms of urinary diversion after cystectomy. PMID- 2577196 TI - Endometrial cancer. PMID- 2577197 TI - Epidemiology of endometrial cancer. PMID- 2577198 TI - Multiagent chemotherapy of endometrial carcinoma. PMID- 2577199 TI - In vitro sensitivity of human endometrial cancer to cytotoxic and biologic agents. PMID- 2577200 TI - Surgical management of endometrial cancer. PMID- 2577201 TI - Peritoneal cytology in endometrial carcinoma. AB - The ultimate role played by peritoneal cytologic evaluation in endometrial cancer remains somewhat ill-defined. Proper assessment of peritoneal cytology as an independent risk factor awaits a prospective study in which patients with malignant peritoneal cytology and surgical Stage I lesions are not treated and survival is compared to controls with negative cytology. Such a study is unlikely to be done, given results available from retrospective analyses and the large number of patients needed to complete such a trial. Whether therapy is needed and which type to use in patients with malignant cytology remain uncertain. Half of these patients will presumably require pelvic radiotherapy for adnexal, nodal, or other pelvic spread. Potish et al. have advocated the use of whole-abdominal radiotherapy in such patients, with favorable results. In patients without extrauterine spread, Creasman et al. have championed the postoperative use of intraperitoneal radioactive phosphate. They based their recommendation on survival results in a group of 23 patients with positive washings who were treated with intraperitoneal radioactive chromic phosphate. In this group, the recurrence rate was reduced, when compared to historic controls, to 13% (3/23), all of whom had extra-abdominal recurrences. Soper et al. confirmed the safety of postoperative radioactive chromic phosphate in doses of approximately 15 millicuries in patients with endometrial cancer. In their study of 65 patients, 56 had percutaneous catheter placement under local anesthesia after laparotomy. In one patient, the catheter could not be used because of poor distribution of the technetium Tc 99m sulfur colloid tracer, and in a second subject, fever and peritoneal signs suggesting bowel perforation led to removal of the insertion catheter. No other significant problems were encountered in 48 patients treated with radioactive chromic phosphate without other therapy. In contrast, five of seventeen patients who received external pelvic radiotherapy in addition to radioactive chromic phosphate suffered bowel complications requiring surgical intervention. Two of these patients died of operative complications, suggesting that radioactive chromic phosphate cannot be safely combined with standard dose external radiotherapy. In a retrospective series, Mazurka et al. intimated that adjunctive chemotherapy might be useful in patients with malignant cytology, but such an approach is untested. A prospective randomized study of radioactive chromic phosphate, whole abdomen radiotherapy, or adjunctive chemotherapy versus no treatment in patients with malignant peritoneal cytology is clearly needed. PMID- 2577202 TI - The role of preoperative radiotherapy in the treatment of carcinoma of the endometrium. PMID- 2577203 TI - Radiotherapy in the management of nodal and peritoneal metastases. PMID- 2577204 TI - Carcinoma of the endometrium and hormonal receptors. PMID- 2577205 TI - Systemic therapy with single agents for advanced or recurrent endometrial carcinoma. PMID- 2577206 TI - [Fowler-Stephens orchidopexy]. AB - The authors, after a short report on intraabdominal cryptorchidism and its surgical problems, illustrate the Fowler-Stephens' technique with its advantages as they result from their experience, although limited. Some operative stages, considered essential, are emphasized. PMID- 2577208 TI - [Role of gonadal phlebography in the diagnosis of cryptorchidism]. AB - The authors describe the diagnostic procedures for testicular localization in patients with non palpable undescended testes. They consider the procedures as invasive and non invasive. The first procedures include ultrasonography, C.T. and N.M.R., the second ones laparoscopy, selective arteriography and venography of the spermatic vessels. Anatomy of spermatic venous system and catheterization techniques are described. Conclusions are that when non invasive procedures fail to localize the testis, gonadal venography is the procedure of choice for the correct diagnosis. Preoperative testicular localization often reduces the extent of surgical exploration and the anesthesia time. These patients have to undergo surgical treatment also when gonadal venography shows a blinding end vein in the inguinal canal, because of the intra-abdominal testis possible degeneration. PMID- 2577207 TI - [Somatostatin in the treatment of acute pancreatitis and prevention of postoperative acute pancreatitis. Personal experience]. AB - Authors' personal experience is reported in the use of somatostatin for the treatment of acute pancreatitis and after bilio-pancreatic surgery. The drug has proved to be highly effective in reducing the pain and in controlling the biohumoral balance. The preliminary results appear to confirm the opinion that somatostatin is a major therapeutic tool in the treatment of bilio-pancreatic diseases. PMID- 2577209 TI - [Effect of external divalent cations on beta action of isoprenaline in the smooth muscle of guinea pig taenia coli]. PMID- 2577210 TI - [Effects of adrenergic beta receptor agonists on tracheal smooth muscle of rabbits and the desensitization phenomenon]. PMID- 2577211 TI - [Effect of beta 2 agonists on smooth muscles of the bladder and on striated muscles of the urethra]. PMID- 2577213 TI - [The use of restriction fragment length polymorphisms for diagnosis: the estimation of diagnosable rate of more than one genetic markers]. AB - As a codominant genetic marker, restriction fragment length polymorphisms, referred as RFLPs, has been widely applied to the prenatal diagnosis of some genetic diseases. To evaluate the usefulness of the genetic markers in prenatal diagnosis, a parameter, the diagnosable rate or the proportion of diagnosable matings is proposed in the cases of two or more genetic markers. The estimation is applicable to the cases of autosomal recessive and dominant disease, as well as those of X-linked recessive and dominant diseases. The diagnosable rate of two or more genetic markers is based on the distribution of haplotypes. Thus in the case when n genetic markers being used, the disagnosable rate, or the fraction of matings in which the A2A2 fetus could be confirmed or ruled out by the fetal restriction fragment patterns in the A1A2 X A1A2 matings, is expressed as follows: [formula: see text] where A2 is a recessive deleterious gene, yi is the frequency of the genotype of ith type individuals, and M is the total number of combination of n markers. It is a valuable strategy to use more than one genetic markers in order to increase the diagnosable rate. By using the data of the distribution of haplotypes, it is easy to find the most usable genetic markers or their combinations. PMID- 2577212 TI - [Enzymatic diagnosis of alcoholism-induced damage of internal organs]. AB - ++Post-alcoholic lesion of liver, pancreas, and heart muscle was estimated by measurement of some enzymes activity. Alcoholic in-patients were divided into two groups in regard to the age and the length of the disease. The activity of enzymes in the blood was measured by kinetic methods using the RA-1000/Technicon analyser. It was shown that the increase of activity of alanine aminotransferase (AlAT), gamma-glutamyltransferase (GGTP), and alcohol dehydrogenase (ADH) may indicate the ++post-alcoholic liver damage, while increase of activity of alpha-+ amylase and ++leucine aminopeptidase (LAP) may be useful for the diagnosis of pancreas lesion, and creatine kinase (CK) as well as lactate dehydrogenase (LDH) for the evaluation of postalcoholic lesion of the heart muscle. PMID- 2577214 TI - Neuromodulation of mucosal immunity. PMID- 2577215 TI - First conference of the European Society for Analytical Cellular Pathology, Schloss Elmau, FRG, 12-17 November 1989. Abstracts. PMID- 2577216 TI - Second International Congress on Schizophrenia Research. San Diego, California, April 1-5, 1989. Abstracts. PMID- 2577217 TI - [Neuromas of the oral cavity]. PMID- 2577218 TI - Changes in the activity of glutamate related enzymes in cerebral cortex, during insulin-induced seizures. AB - The activity of glutamate related enzymes and the concentration of glutamine, glutamate and gamma-amino n-butyric acid (GABA) were investigated in the cerebral cortex of rats, in different stages of insulin-induced hypoglycemia. Hypoglycemia was produced by intraperitoneal injection of insulin 0.05-100 units per kg body weight. The minimum required dose to produce irreversible severe hypoglycemia was 0.5 units/kg. In 85% of the cases an insulin induced hypoglycemic convulsion, was achieved 130-150 minutes after injection. Blood glucose levels during insulin induced seizures ranged between 8-15 mg%. In the range of 0.5-100 u insulin/kg the degree of hypoglycemia and the onset of convulsions were identical. The concentration of glutamine was significantly reduced during convulsive and postconvulsive stages. Glutamate and GABA concentrations were reduced significantly in all stages of insulin-induced hypoglycemia. The decrease in glutamine concentration was concurrent with an increase in the activity of its degradative enzyme, glutaminase. This was apparent at the preconvulsive, convulsive and postconvulsive stages. The activity of other enzymes related to energy production such as glutamate dehydrogenase (GDH), glutamate transaminase (GPT) and aspartate aminotransferase (AAT) were also increased. The activity of glutamine synthase (GS) was unaffected by hypoglycemia. Insulin induced changes in glutamine, glutamate and their related enzymes could not be attributed to convulsion since a similar pattern of changes was observed in the preconvulsive and postconvulsive stages, and no changes were detected following picrotoxin induced seizures. PMID- 2577220 TI - Effects of single oral doses of bromazepam, buspirone and clobazam on performance tasks and memory. AB - Three anxiolytic drugs (bromazepam 3 mg, buspirone 10 mg, and clobazam 10 mg p.o.) were evaluated for their effects on memory, psychomotor performance and subjective response in a double-blind, placebo-controlled, crossover study in 20 healthy volunteers. At each session, measurements were made before and 2 and 6 h after drug administration. The psychometric tests used were the images test, digit/symbol substitution test (DSST), choice reaction time (CRT), and critical fusion frequency (CFF). Free recall after 30 s in the 2-hour session was altered for all 3 drugs as compared to placebo (p less than 0.01), but in the 6-hour session only bromazepam showed a significant difference (p less than 0.05). The number of symbols reproduced by subjects during DSST was significantly decreased by bromazepam and buspirone as compared to placebo (p less than 0.05), whereas clobazam showed no differences with placebo. Analysis of variance for all four treatments (the 3 drugs and the placebo) showed no differences at recognition time or for motor response in CRT, except between bromazepam and clobazam after 6 h (p less than 0.05). None of the drugs altered performance during CFF (except bromazepam), and clobazam actually improved performance. All the drugs studied disturbed acquisition phenomena or restitution of memory; however, only bromazepam and buspirone significantly modified performance during DSST and disturbed the recognition and processing of sensory data. PMID- 2577219 TI - The induction of T cell-mediated cytolysis by monoclonal antibodies against the T cell receptor/CD3 complex. PMID- 2577221 TI - Release of [3H]dopamine from rat prefrontal cortex: modulation through presynaptic cholinergic heteroreceptors. AB - The release of tritiated dopamine ([3H]DA) from slices of the rat prefrontal cortex was studied using a superfusion technique. Release appeared to be voltage dependent and also dependent on external Ca2+, suggesting the presence of a specific neurotransmitter release mechanism. gamma-Aminobutyric acid (GABA), aspartate, glutamate and serotonin had no effect on either basal DA release or K(+)-stimulated release. Carbachol, a cholinergic agonist, inhibited K(+) stimulated DA release. The results demonstrate that cholinergic heteroreceptors on dopaminergic terminals of the prefrontal cortex modulate DA release. PMID- 2577222 TI - Benzodiazepines decrease the release of [3H]noradrenaline and of [3H]acetylcholine in the cat superior cervical ganglion. AB - The effects of two benzodiazepines, diazepam and clonazepam, were studied on the release of [3H]noradrenaline and of [3H]acetylcholine elicited by preganglionic stimulation of the cat isolated superior cervical ganglion and on the contractile responses evoked by either nerve stimulation or exogenous noradrenaline in the cat isolated nictitating membrane. Both 10 microM diazepam and 10 microM clonazepam reduced by approximately 50% the release of [3H]noradrenaline and of [3H]acetylcholine in the cat ganglion whereas they did not modify the contractile responses in the nictitating membrane. It is concluded that benzodiazepines are also peripheral neuroactive agents and that they exhibit a tissue-selective action within the same animal species. PMID- 2577223 TI - Modulation of mechanosensory threshold in Aplysia by serotonin, small cardioactive peptideB (SCPB), FMRFamide, acetylcholine, and dopamine. AB - Mechanosensory threshold of tail sensory neurons in Aplysia was tested after injecting the tail with neuromodulators known to affect defensive behavior in this animal. Serotonin (5-HT) and small cardioactive peptide (SCPB) reduced peripheral threshold, while FMRFamide, acetylcholine (ACh), and dopamine increased threshold. FMRFamide and ACh also reduced spontaneous activity of sensory neurons. Glutamate and taurine had no effect. SCPB effects persisted for 15-30 min after washout. Functional similarities between peripheral and central effects of these neuromodulators support the hypothesis of coordinate modulation of both regions of the sensory neuron by the same set of modulators following noxious stimulation. PMID- 2577224 TI - Low-frequency activation of the NMDA receptor system can prevent the induction of LTP. AB - In rat hippocampal slices bathed in Mg2(+)-free medium tetanic stimulation generally failed to elicit long-term potentiation (LTP) in the Schaffer collateral-commissural pathway. However, LTP could be induced in the same slices following the re-introduction of 1 mM Mg2+. In Mg2(+)-free medium, LTP could be induced in the presence of 20 microM D-2-amino-5-phosphonovalerate (APV) but was blocked by increasing the APV concentration to 200 microM. The lower concentration of APV is sufficient to prevent N-methyl-D-aspartate (NMDA) receptor activation during low-frequency transmission but not during the tetanus. We suggest therefore, that certain types of activation of the NMDA receptor system can disable the LTP induction mechanism. PMID- 2577225 TI - Responses of spinal dorsal horn neurones evoked by myelinated primary afferent stimulation are blocked by excitatory amino acid antagonists acting at kainate/quisqualate receptors. AB - The effects of excitatory amino acid antagonists on responses, evoked by myelinated primary afferent stimulation, in neurones of the spinal cord dorsal horn has been investigated in an isolated hemisected spinal cord preparation from the neonatal rat. The first evoked action potential of most responses was reversibly blocked by either 5 mM kynurenic acid (80%) or 10 microM CNQX (91%). The small latency variability and the ability of some of these responses to follow repetitive stimulation suggested that they were evoked monosynaptically. The selective NMDA receptor antagonist, CPP, blocked some later components of responses consisting of bursts of action potentials but not the first evoked action potential. The results support the suggestion that myelinated primary afferents release excitatory amino acids which act at kainate/quisqualate receptors. PMID- 2577226 TI - The interaction of cholecystokinin and its fragments with norepinephrine in the circulatory system of diabetic rats. AB - The interaction of cholecystokinin (CCK-33) and its fragments, C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4) with norepinephrine (NE) was studied in rats with streptozotocin (STZ)-induced diabetes. The rats, male Wistar, were divided into three groups: control, diabetic and insulin-treated diabetic. Twenty-eight days after STZ administration, the systolic and diastolic arterial blood pressure, heart rate and the function of the heart isolated by the Langendorff method were studied. NE caused a rise in systolic blood pressure in the control and insulin-treated diabetic rats, the opposite effect of NE was observed in diabetic rats. NE had no effect on heart rate in any of the groups studied. CCK-33 potentiated the hypertensive effect of NE in the control rats reduced the hypertensive effect of this amine in diabetic rats treated with insulin and its hypotensive effect in the diabetic rats. CCK-8 did not change the NE effect on arterial blood pressure in the control and insulin-treated diabetic rats but did reduce the hypotension caused by NE in diabetic rats. CCK-4 did not change the effects of NE in any of the groups. NE induced an increase in cardiac contraction amplitude in all rats but its positive inotropic action was found to be the weakest in the diabetic rats. Administration of CCK-33 did not change the positive inotropic effect of NE in any of the groups but did, however, weaken its influence on heart rate in diabetic rats and insulin-treated diabetic rats. CCK-8 reduced the positive inotropic action of NE but did not affect its chronotropic effect. CCK-4 had no effect on the action of NE in any of the groups. Diabetes can change the response of alpha-adrenergic system to CCK-33 and NE. Insulin partially normalized the circulatory system response in the diabetic rats. PMID- 2577227 TI - [Clinico-therapeutic observations in the neuroleptic malignant syndrome]. AB - The special literature of the last two decades has mentioned repeatedly the occurrence of a "malignant neuroleptic syndrome", a severe, and not too rare complication of therapy with neuroleptic drugs. The authors make an analysis of 17 cases, and discuss the conditions of the development, the symptomatology and the treatment of the malignant neuroleptic syndrome. Due to the fact that the use of neuroleptics has been introduced in other fields of medicine the authors consider that information of physicians of all specialties with regard to this severe complication of neuroleptic therapy is useful. PMID- 2577228 TI - [Laborious conditions]. PMID- 2577229 TI - Glutamine synthetase in Lupinus luteus. Identification and preliminary characterization of nodule-specific cDNA clone. AB - Two glutamine synthetase (GS) cDNA clones from L. luteus were identified and characterized. The nucleotide sequence analysis proved that they represent highly homologous but distinct mRNA species. Northern blot hybridization revealed that pc LINGS encodes the nodule-specific subunit of the GS while pcLIGS1 represents the nonspecific one present in nodule tissue as well as in uninfected roots. PMID- 2577231 TI - 3rd Cardiovascular Pharmacotherapy International Symposium. October 15-19, 1989. Abstracts. PMID- 2577230 TI - Haplotype analysis of phenylalanine hydroxylase alleles in polish families with phenylketonuria. AB - Eight polymorphic restriction enzyme sites at phenylalanine hydroxylase locus from the parental chromosomes in Polish families with phenylketonuria were analyzed. Among 28 chromosomes studied, we identified haplotypes found within the Danish population. Haplotype 2 has been found in 25% of affected alleles. One of the patients studied is homozygous for this haplotype. PMID- 2577233 TI - The molecular basis of beta thalassaemia in Bulgaria. AB - Bulgaria is in a geographical area where beta thalassaemia is relatively common. The frequency of carriers is 2 to 3% of the population. Data on the molecular characteristics of the disorder were obtained from the study of 33 homozygous patients and 57 beta thalassaemia carriers. As in other Mediterranean ethnic groups, haplotype I and the splicing mutation in IVS-1 nt 110 are the most common. Haplotype V is second in frequency and is associated with three different mutations. The second most common mutation, beta null 39, is found in association with haplotype II in 80% of cases. A rare haplotype, possibly resulting from a crossover between a haplotype II and a haplotype V chromosome, was found in two thalassaemia carriers in association with frameshift 6. Altogether four mutations (IVS-1 nt 110, beta null 39, frameshift 6, and IVS-1 nt 6) account for 67% of the thalassaemia chromosomes. Their detection would permit direct fetal DNA analysis in 84% of the families studied (45% fully informative). RFLP analysis (haplotype plus AvaII psi beta) is 100% informative in 79% of the high risk families. PMID- 2577234 TI - [Distribution of the main species of medically important Culicidae on the Isle of Youth]. AB - The distribution of the main culicide species of medical significance in the Isle of Youth is determined, and an assessment of the major areas of influence of these species as well as future prospects is made. Twenty-seven culicide species from 8 genera--19 of which are reported as medically significant in the literature--are found. By way of conclusion recommendations for vector control in the Isle of Youth are provided. PMID- 2577232 TI - Eye movements during sleep. PMID- 2577235 TI - [The RFLPs of St14/Taq I in Chinese and its application to gene analysis and prenatal diagnosis of hemophilia A]. AB - The genomic DNA fragment St14 (DXS52) is located in q28 region of X chromosome that also contains the hemophilia A locus. The RFLPs of St14/Taq I in Chinese were studied. The frequency of allele 7A (3.6 kb) is 31%, which is obviously different from the data reported abroad. By use of the RFLPs, 8 families with hemophilia A were analysed, including 1 case for first trimester prenatal diagnosis at risk of hemophilia A. PMID- 2577236 TI - [Role of somatostatin in the treatment of intestinal fistulas]. AB - Somatostatin is a peptide hormone which inhibits the secretion of the growth hormone, and has proved to be a powerful inhibitor of exocrine pancreatic, gastric and intestinal secretion. It was therefore used as an adjuvant therapy in the conservative treatment of two children of eight and nine years old with fistulas of the small intestine. The first case was a colonic fistula for cecal defect, surgical intervention was carried out because treatment during 14 days with hormonal treatment after the third consecutive day of somatostatin application. In this study the authors present their experience with somatostatin, with particular emphasis on the indications contraindications, doses and lines for administration. PMID- 2577237 TI - [Biochemical profile of the liver of calves aged 1 to 10 days]. AB - The biochemical hepatic profile analysis was performed in 252 neonatal Holstein Friesian calves, aged from 1 to 10 days. The activities of glutamic oxalacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase and gamma glutamyltransferase as well as beta-glucuronidase were estimated in blood serum and in faeces. A significant decrease in glutamic oxalacetic and glutamic pyruvic transaminase, alkaline phosphatase as well as gamma-glutamyltransferase was observed in the blood serum while in the faeces the peak of activity took place between 4-5 days for beta-glucuronidase and glutamic pyruvic transaminase and 7-8 days for glutamic oxalacetic transaminase, alkaline phosphatase and gamma glutamyltransferase. No significant relation was found between activities of the examined enzymes in blood serum and faeces. Determination of GOT and GPT, AP, GGTP in serum may be used to describe liver function in neonatal calves. No changes in total bilirubin and total protein levels in blood serum and faeces were observed during the first 10 days of calf life. PMID- 2577239 TI - [Effect of adrenergic drugs and exploitation on sexual reflexes and semen properties in Polish large white boars aged 2-3 years]. AB - The effect of exploitation and adrenergic system drugs on sexual reflexes and properties of the semen in somatically mature Polish Large White boars has been presented. At the first stage 8 males were exploited twice a week. Then, previous to semen collection, the animals were given beta-adrenolytic (Propranolol- Polfa), after 30 minutes followed by the preparation Levonor--Polfa (alpha adrenomimetic). 15 minutes after last injection the semen was collected, this procedure having been repeated twice a week. At the second stage of the experiment the same males were exploited once a week. Like in the first stage, the animals were given the same doses of the drugs in the same sequence. 15 minutes after last injection the semen was collected once a week. At the third stage of the experiment the boars were exploited every day. Again, like in the previous stages, the animals were given the above mentioned beta-adrenolytic and alpha-adrenomimetic to collect the semen 15 minutes after last injection. In all the stages of the experiment 6-8 ejaculates were collected from each boar. Apart from preliminary assessment of concentration and morphology of spermatozoons there was determined the level of protein and activity of selected enzymes in the semen. The sexual drive as well as the time of searching reflex and ejaculation were observed. The drugs applied have been proved to be able to prolong the time of ejaculation reflex. Simultaneous application of beta-adrenolytic and alpha adrenomimetic to animals exploited twice a week appeared to increase the number of spermatozoons in the whole ejaculate, the percentage of spermatozoons with proper movement and the activity of GGT and fucosidase. Intensive exploitation of a boar with parallel application of the preparations described bring about a gradual decrease in spermatozoons and protein in the ejaculate as well as in the activity of hyaluronidase in its plasma and in conversion to mg protein of semen plasma. PMID- 2577238 TI - [Usefulness of selected enzymatic methods for coprological examination of calves]. AB - Methodical analysis of glutamic oxalacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase and gamma-glutamyltransferase activity in calves faeces was performed. The faeces from both healthy and diarrheic Holstein Friesian calves, aged from 1 to 10 days, were used. For each enzyme the repetition and representativity of single determination was examined respectively in soft and dry matter. The results of our analysis show that normal enzymatic methods may be used for the determination of glutamic oxalacetic and glutamic pyruvic transaminases as well as gamma-glutamyltransferase. Further investigation methods are needed for determination of alkaline phosphatase activity in faeces. PMID- 2577241 TI - Depression as a public health issue. A satellite international symposium of the XVth Congress of the International Association of Suicide Prevention. Proceedings. PMID- 2577240 TI - Expression of homeobox genes in human erythroleukemia cells. AB - Because homeobox-containing genes play a major role in embryogenesis and tissue identity in Drosophila and because similar genes encode tissue-specific transcription factors in mammalian cells, we hypothesized that homeobox genes might plan a role in hematopoietic differentiation and lineage commitment. We therefore surveyed a number of human leukemic cell lines for expression of homeobox-containing genes by Northern gel analysis with probes from the Hox 2 cluster of homeobox genes on chromosome 17. We observed transcripts for Hox 2.1, 2.2, 2.3 and 2.6 in the erythroid line HEL and for Hox 2.3 and 2.6 in the erythroid line K562. Using homeobox-specific probes we confirmed that the transcripts visualized contained the homeodomains for each gene as well as the flanking sequences. The myeloid lines HL60, KG1 and U937 did not express specific transcripts for any of the 4 genes studied. However, all these cell lines demonstrated bands when probed at low stringency with certain Hox 2 probes, indicating the expression of other homologous but as yet unidentified homeobox genes. Expression of Hox 2.3 and 2.6 was seen in some T and B lymphoid cell lines. Induction of differentiation in HEL cells resulted in complex modulation of expression of the Hox 2 genes. We have therefore observed erythroid-restricted expression of certain Hox 2 homeobox containing genes in human erythroid cell lines and modulation of that expression with differentiation, suggesting a role for these genes in the regulation of hematopoiesis. Different homeobox genes appear to be expressed in non-erythroid leukemic cell lines. PMID- 2577242 TI - Moving ahead yet falling behind. A critical appraisal of some trends in contemporary depression research. AB - The progress of psychiatry over the past few years is impressive. That process, however, is nonlinear and in this paper three developments in depression research are discussed and thought to be counterproductive. First, the depression classification as institutionalized by the DSM-III is an unfocused and confusing one. The regular revisions, moreover, largely based on the opinions of experts rather than on the research by experts, add to the confusion. Second, the preoccupation of biological psychiatry with nosology is seen as a growth inhibiting factor. The functional/dimensional approach searching for correlations between biological and psychological dysfunctions, an approach we have been advocating for many years, seems to have great potential and deserves to be included in mainstream biological psychiatry. Finally, the 'biologization' of depression research went too far. The conception of depression as a brain disease is a 'terrible simplification', even for the syndrome considered to be the most 'biological' of all: major depression, melancholic type. Psychological determinants of the brain dysfunctions underlying depressive disorders deserve as much scientific scrutiny as their biological counterparts. The mind should not be the soft belly of (biological) psychiatry. PMID- 2577243 TI - 10th World Congress of the International College of Psychosomatic Medicine. Madrid, October 7-11, 1989. Proceedings. PMID- 2577244 TI - [Benzodiazepines tolerance and dependence: a case report]. AB - This is a case report of benzodiazepine abuse and dependence with tolerance to some (psychomotor sedative) but not all (memory) of the BDZ effects. A withdrawal syndrome which included intensification of paranoid personality traits, was observed. PMID- 2577245 TI - Superantigens: interaction of staphylococcal enterotoxins with MHC class II molecules. AB - We have shown that the staphylococcal enterotoxins and TSST specifically bind to MHC class II molecules. This binding to class II molecules is a prerequisite for the function of these bacterial exotoxins as T cell mitogens in vitro. While SEA bound all class II molecules tested with respect to isotype and allotype, the other enterotoxins were limited in binding by the class II isotype. In contrast to conventional antigen, the nature of enterotoxin interactions with MHC enables them to stimulate class I-restricted CD8+ T cells, most likely due to the ability of SEs to engage the T cell receptor based solely on V beta usage. Finally, in addition to activating adjacent T cells, the enterotoxins and TSST can evoke responses from the class II-bearing cells to which they bind. Enterotoxin/TSST effects on cells that bear class II molecule "receptors", in addition to their induction of T cell hormones such as interleukin-2 and interferon-gamma, provide possible explanations for some of the symptomatology seen with these bacterial exotoxins and also implicate MHC class II molecules as signal-transducing receptors. PMID- 2577247 TI - Antinociceptive effects of localized administration of opioids compared with lidocaine. AB - To study possible antinociceptive effects of perineurally administered opioids, the rat infraorbital nerve block (IONB) model was employed for investigations of opioids (morphine, meperidine, buprenorphine, ethylketocyclazocine, and fentanyl) of differing receptor selectivity and physicochemical properties such as lipid solubility. Only meperidine in doses greater than 1 mg/kg produced localized analgesia, the duration of which increased dose-dependently. Naloxone failed to counteract the analgesic effects of meperidine. It is concluded that meperidine exerted its effect by a local anesthetic action and not by the activation of opioid receptors in the peripheral nerve. The local anesthetic potency of meperidine was compared with that of lidocaine in peripheral nerve blocks (IONB in rats and sciatic nerve block in guinea pigs), in central nerve blocks (epidural anesthesia in guinea pigs and spinal anesthesia in mice), and in infiltration anesthesia in guinea pigs. Time to onset of block was generally longer for meperidine. Equal amounts of the drugs produced motor blocks of similar durations except in epidural anesthesia where meperidine was clearly shorter. Sensory blocks were longer with meperidine than with lidocaine when applied in equal amounts to the infraorbital nerve and subarachnoidally. The two agents caused a similar duration of sensory block in infiltration anesthesia. Meperidine was shorter than lidocaine in epidural anesthesia. The characteristics of blocks induced by the two agents may be explained by structural differences and associated differences in physicochemical properties such as lipid solubility and pKa. PMID- 2577248 TI - [Formation of the functional synapse in the cultured nerve cell]. AB - Recent progress concerned with the formation of the functional synapse among cultured nerve cells was reviewed. By means of newly developed techniques, such as the patch-clamp method, selective nerve-cell culture and optical measurement of the intracellular Ca concentration, our knowledge about presynaptic and postsynaptic functions markedly increased in this decade. Especially in the fields of differentiation of the neurotransmitter synthesis and releasing mechanism, neurite-outgrowth and specific cell-to-cell adhesion, identification of neurotransmitters-receptors and corresponding second messenger systems, great progress has been made. Actually functional synapses were formed between neurons cultured from spinal cord, cerebellum, hippocampus, cerebral cortex and other brain regions. Basic problems such as identification of neurotransmitters and their receptors, analysis of network functions, synchronized activities and cell death mechanism have been studied using above culture systems. Although molecular mechanism underlying the specific synapse formation has not been understood well, this problem would be resolved in the near future using the nerve cell culture. PMID- 2577246 TI - Leukocyte adhesion proteins: their role in neutrophil function. AB - In conclusion, the leukocyte proteins of the CD11/18 complex are highly conserved members of the integrin family in mammalian species. They play a key role in phagocytic and adherence mediated activities of neutrophils and appear to be centrally involved in adhesion to endothelial cells as well as transendothelial migration. Their importance in these processes has been documented by the occurrence of the disease now called leukocyte adhesion deficiency and the functional effects of a variety of monoclonal antibodies directed at different epitopes on the heterodimeric glycoprotein chains. These antibodies, as well as those directed at endothelial cell ligands for leukocyte adhesion proteins or peptides which mimic the functional epitopes, offer opportunities to manipulate or modify the inflammatory response in vivo where neutrophil accumulation or action can be harmful. They can also be employed to dissect out the role of PMNs in various repair processes such as wound healing. While bone marrow transplantation can ameliorate the deleterious consequences of severe LAD, continued elucidation of the multiple molecular mechanisms responsible for this disease will pave the way for its future genetic correction. PMID- 2577249 TI - [Current advances in neural transplantation]. AB - In the present study, we obtained genetically manipulated non-neuronal cells which synthesize a catecholamine precursor for future use in the intracerebral grafting. Human type 1 tyrosine hydroxylase (TH, EC 1. 14. 16. 2) cDNA was inserted into eukaryotic expression vector pKCRH2 and was co-transfected into C6 cells with plasmid pSV2neo. Expression of the TH minigene was screened by immunocytochemical staining with TH antibody and immunoblotting analysis. Several clones of the C6 transfectants that produce TH molecules were obtained. These cells showed TH activity and the product, L-DOPA, was detected intracellularly due to the absence of L-amino acid decarboxylase (AADC, EC 4. 1. 1. 28) activity. It was found that a large amount of L-DOPA was released from the cells into the culture medium. These transfectants were transplanted into rat brain and the expression of TH was examined immunohistochemically. At the 10th day following transplantation, a mass of C6 cells which was heavily stained with TH antibody was observed in the brain. These findings may provide us an opportunity to investigate the effects of intracerebral transplantation of non-neuronal cells that produce catecholamine or its precursor. PMID- 2577250 TI - [Human neuroblastoma cell line TNB1 and its biological characteristics]. PMID- 2577251 TI - Continuous high thoracic epidural administration of bupivacaine with sufentanil or nicomorphine for postoperative pain relief after thoracic surgery. AB - In a prospective study, 40 patients who had undergone thoracotomy for lung resection were investigated. During operation, all patients received intravenous anesthesics, halothane and an initial dose of bupivacaine 0.5% with epinephrine 5 micrograms.ml-1 (5 to 10 ml) by thoracic epidural catheter. One hour after the initial dose of bupivacaine 0.5% with epinephrine, patients were divided in two groups for analgesia, the sufentanil group (50 micrograms sufentanil in 60 ml bupivacaine 0.125%) or the nicomorphine group (3 mg nicomorphine in 60 ml bupivacaine 0.125%) by a continuous epidural infusion (5 to 10 ml.h-1) for three days. Cardiovascular differences between the sufentanil group and the nicomorphine group were not statistically significant per- or postoperatively. The minimum respiratory frequency on either Day 1, 2, or 3 was 12 breaths.min-1 in the sufentanil group, corresponding to a PaCO2 of 32 mmHg, and 11 breaths.min 1, corresponding to a PaCO2 of 41 mmHg in the nicomorphine group. On Day 1, the PaCO2 in the sufentanil group was significantly lower (p less than 0.01), but in both groups the PaCO2 on Day 1 was significantly higher than the preoperative value. An inverse visual analogue pain scale (0 to 10 IVAS) showed mean scores above 7.5 for all patients during the three days. Scoring pain relief during exercise showed a significant difference in favor of the sufentanil group on Days 1, 2, and 3 (p less than 0.0008). The mean plasma bupivacaine level doubled every day, 138 ng.ml-1 on Day 1, 290 ng.ml-1 on Day 2, and 596 ng.ml-1 on Day 3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2577252 TI - Epidural sufentanil for analgesia for labor and delivery. AB - Six groups of ten women each in active labor at term had epidural catheters placed in the usual manner and received a 3 mL test dose of 2% lidocaine with epinephrine. Groups 1-6 received, respectively, 5, 10, 20, 30, 40 and 50 micrograms of sufentanil diluted to 10 mL with normal saline. Significantly effective analgesia was provided at all sufentanil doses studied, with pain scores decreasing from 8.1 +/- 0.2 at baseline to 2.9 +/- 0.3 at 10 minutes and 1.1 +/- 0.2 at 30 minutes (mean +/- SEM, average for all groups). The duration of analgesia showed a significant (p less than 0.05) relation to sufentanil dose, increasing from 79.1 +/- 11.3 minutes (5-micrograms group) to 137.8 +/- 17.2 minutes (50-micrograms group). There were no serious maternal side effects, although ten patients developed pruritus, four became dizzy, two experienced mild sedation, and one had transient hypotension. No neonatal side effects occurred. Maternal serum sufentanil levels remained below the sensitivity of the assay, or 0.1 ng/ml. PMID- 2577253 TI - Maternal analgesia and neonatal effects of epidural sufentanil for cesarean section. AB - This study was designed to evaluate the maternal intraoperative and postoperative analgesia and neonatal effects of adding sufentanil to epidural anesthesia for cesarean section before the skin incision. Forty-five multipara were randomized in three equal groups to receive sufentanil 80 micrograms, 50 micrograms, or saline with the epidural lidocaine. Intraoperative and postoperative analgesia and side effects were recorded. Infants were evaluated by Apgar score at one and five minutes and by Neurologic and Adaptive Capacity Score and Early Neonatal Neurobehavioral Scale at one, four and 24 hours of life. Superior analgesia, with no intraoperative requirements for supplemental narcotics, was obtained when either 80 micrograms or 50 micrograms sufentanil were added to lidocaine. Postoperative analgesia was prolonged after sufentanil, but side effects increased with the greater dose. The infants whose mothers received 80 micrograms sufentanil showed a mild neurobehavioral depression. It is therefore concluded that the addition of 50 micrograms of sufentanil improves both intraoperative and postoperative analgesia without significant neonatal effects. PMID- 2577254 TI - Epidural sufentanil for cancer pain control in outpatients. AB - Fifteen patients with cancer pain refractory to other methods of pain control were treated with epidural sufentanil. They all suffered from very severe or unbearable pain but had expressed the wish to spend the last period of their lives at home. On the first day of hospitalization, an epidural catheter and a portal catheter were implanted under local anesthesia. Sufentanil was delivered by a portable infusion pump into the portal catheter. The patients remained a further 2-3 days in hospital to titrate the infusion rate to their specific needs and to monitor pain relief and possible side effects. In the home situation, the patients were supervised by their general practitioners. Nine patients had epidural sufentanil as their sole analgesic till they died; six patients needed adjunctive nonepidural medications. There were no epidural- or portal-catheter related infections or cases of respiratory depression. After 1651 patient treatment days, we have found continuous epidural sufentanil infusion to be a safe and effective method for cancer pain control in outpatients. PMID- 2577255 TI - Role of blocking TSH receptor antibodies on the development of hypothyroidism and thyroid atrophy in primary myxedema. AB - We studied blocking type TSH receptor antibodies in 28 patients with primary myxedema and 21 patients with goitrous Hashimoto's thyroiditis by measuring the ability of their IgG to inhibit TSH binding to its receptor, and to inhibit TSH stimulated cAMP increases and 3H-thymidine incorporation in a rat thyroid cell line, FRTL-5. The incidences of TSH binding inhibitor immunoglobulin (TBII), thyroid stimulation blocking antibody (TSBAb) and thyroid growth blocking antibody (TGBAb) in patients with primary myxedema were 53.6%, 75% and 65.2%, respectively. However, in goitrous Hashimoto's thyroiditis, these were 14.3%, 0% and 17.7%, respectively. These antibodies inhibited the receptor binding of 125I bTSH dose-dependently, and also inhibited dose-dependently not only TSH stimulated but also Graves' IgG-stimulated cAMP increase and 3H-thymidine incorporation. TBII activities of patients with primary myxedema were significantly correlated with both their TSBAb (r = 0.665; p less than 0.01) and TGBAb (r = 0.618; p less than 0.01) activities. Thirteen patients whose TBII activities were more than 50% had both strong TSBAb (75.1-100%) and TGBAb (57.4 100%) activities. Transient neonatal hypothyroidism was found in an infant born to a mother having potent TBII activities. Serum of the baby also had potent TBII activities and the baby's IgG inhibited TSH-stimulated cAMP increase and 3H thymidine incorporation. These data suggest that a significant proportion of patients with primary myxedema have potent blocking type TSH receptor antibodies. These might play a role in primary myxedema causing hypothyroidism and thyroid atrophy through inhibition of TSH-stimulated cAMP generation. PMID- 2577257 TI - A clinical study of hemorrhagic fever with renal syndrome caused by Seoul virus infection. AB - The clinical findings of 29 patients with hemorrhagic fever with renal syndrome (HFRS) caused by Seoul virus were evaluated and compared with the previously reported clinical findings of classic Korean hemorrhagic fever (KHF). The diagnoses of these patients were made by hemagglutination inhibition test. The results were as follows: 1) The disease occurred predominantly in males with a high incidence in the third and fourth decades of life. 2) The highest incidence of the disease occurred in October-December. 3) Major symptoms were fever, abdominal or flank pain, vomiting and myalgia. 4) Major signs were petechia, CVA tenderness, pharyngeal injection, and conjunctival infection, but these signs were much less common than in patients with classic KHF. 5) The treatments were mainly conservative and there was no fatal case in the study subjects. These findings suggest that the clinical course of Seoul virus infection may be much milder than that of classic KHF and the outcome may be more favorable. PMID- 2577256 TI - Pathogenetic role of thyrotropin receptor antibody in the development of hyperthyroidism following primary hypothyroidism. AB - The authors measured thyrotropin binding inhibitory immunoglobulin (TBII), thyroid stimulating antibody (TSAb), and thyroid stimulation blocking antibody (TSBAb) sequentially in patients who developed hyperthyroidism following primary hypothyroidism, and compared changes in these various functional parameters of thyrotropin receptor antibody (TRAb) with clinical manifestations, in order to investigate the role of TRAb in the development of hyperthyroidism following primary hypothyroidism. In a patient with goitrous chronic thyroiditis, TBII, TSAb and TSBAb were not detected at the initial hypothyroid phase. But with appearance of TBII and TSAb, the patient developed hyperthyroidism. In a patient with primary nongoitrous myxedema, initially high TBII and TSBAb were detected without TSAb activity. His TSBAb disappeared and TSAb appeared with development of goiter growth and hyperthyroidism. These two mechanisms, that is, appearance of previously absent TSAb and conversion of TSBAb to TSAb, might play a causative role in the development of hyperthyroidism following primary hypothyroidism. These phenomena might be evidence that Graves' disease, chronic thyroiditis, and primary nongoitrous myxedema are on a continuing spectrum of a common syndrome sharing similar pathophysiology, at least with respect to TRAb. PMID- 2577258 TI - Treatment of social phobia by homework exposure. AB - Ten consecutive patients suffering from DSM-III-R social phobia were treated by homework exposure assignments, without therapist-aided exposure or other cognitive-behavioral methods. The 7 patients who completed therapy displayed highly significant decreases in social phobic symptoms and anxiety. Such improvements were maintained on a 1-year follow-up. PMID- 2577259 TI - N-ras mutation in chemically induced rat brain tumour. AB - Rat brain tumour was induced by treatment with N-ethyl-nitrosourea. Using Southern blot analysis, restriction fragment length polymorphism of N-ras gene was identified. Comparative studies showed that new restriction site did not occur in the DNA of DMN induced renal and liver tumours. The data suggest that the mutation occurring may be specific to the "target" cell or to the structure of carcinogens. PMID- 2577260 TI - Abstracts of the XXII Nordic Paediatric Congress. Reykjavik, Iceland, June 12-16, 1988. PMID- 2577261 TI - Critical review on quantitative autoradiography of D1 and D2 dopaminergic receptors in the striatum of the mammalian brain: differential localization and plastic changes after pharmacological manipulation and dopaminergic input disruption. AB - Major technical progress in the development of computer-based image analysis systems has made possible the entry of autoradiographic and immunohistochemical techniques into a new era where quantification via densitometry and morphometry has become easily accessible. In this context, quantitative biochemical data can be adapted to anatomical and histological resolution. This adaptation is most efficient in the neuroscience fields because of the huge importance of cellular communication via neuronal networks in the nervous system. Therefore, any experimental approach to the brain which considers the brain as a 'black box' appears now as very crude. In fact, subtle heterogeneity in the distribution of biochemical markers can now be demonstrated, as illustrated here by the use of quantitative autoradiography of D1 and D2 dopaminergic receptors in the striatum of the mammalian brain. Also, local adaptive changes resulting from chronic blockade of the dopaminergic input can be detected after repeated treatments with dopaminergic antagonists selective for D1 or D2 receptors or with surgical lesioning of the dopaminergic nigrostriatal pathway. The resulting plastic changes are unevenly distributed throughout the striatal target organ and vary according to the mode of suppressing the dopaminergic flow: direct destruction of the dopaminergic pathway or selective pharmacological manipulation without physical elimination of the dopaminergic cells themselves. All these results are discussed and reviewed in light of the most recent reports in this field. PMID- 2577262 TI - Mitochondrial DNA polymorphism in Calabria (southern Italy). AB - Restriction Fragment Length Polymorphism (RFLP) of mitochondrial DNA (mtDNA) has been investigated in a sample from Calabria (Southern Italy). Seven restriction endonucleases (HpaI, BamHI, HaeII, MspI, AvaII, HincII and PstI) have been employed on 60 mtDNAs from placentas. Two new morphs have been identified (PstI 3Cal and AvaII-24Cal) and the respective polymorphic sites have been located by double digestion. Two new types (74 and 75) have also been identified and their possible origin from other known mtDNA types has been suggested. PMID- 2577264 TI - Characterization of guanylate cyclase in squid photoreceptors. AB - Light causes a rapid, 1.7-fold increase in cyclic GMP concentration in intact squid retinas (Johnson et al. (1986]. To determine whether light-induced changes in cyclic GMP concentration result from activation of guanylate cyclase, we have studied the regulation of guanylate cyclase activity in squid (Loligo pealei) photoreceptors. The enzyme is membrane-associated and activity is enhanced by the detergents Triton X-100 or digitonin. The enzyme requires divalent cations, Mn2+ being preferred over Mg2+. The dependence of enzyme activity on the MnGTP concentration deviates from simple Michaelis-Menten kinetics. Under conditions where a light-induced binding of GTP to the guanine nucleotide regulatory protein can be observed, no light-induced change in guanylate cyclase could be detected. PMID- 2577263 TI - Dopamine synthesis and metabolism in rhesus monkey retina: development, aging, and the effects of monocular visual deprivation. AB - The normal postnatal development, the influence of age, and the effects of visual deprivation on the dopamine system in the retina of rhesus monkeys were examined. The lowest level of retinal dopamine was found at birth. By 3-4 weeks of age, the dopamine concentration had more than doubled. This level remained relatively constant in the retinas of older infants and of adult monkeys up to 34 yr of age. The level of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and the activity of tyrosine hydroxylase did not significantly change as a function of age during the postnatal life span. Monocular occlusion of newborn or infant monkeys for 1-15 months with opaque contact lenses resulted in decreases in the retinal concentrations of dopamine and DOPAC relative to the concentrations in the same animals' unoccluded eyes. Occlusion also resulted in a lower level of tyrosine hydroxylase activity in the retina. Monocular eyelid suture from birth to 15 months of age resulted in less consistent alterations of retinal dopamine and DOPAC levels; tyrosine hydroxylase activity, however, was consistently reduced by lid suture. Thus, dopamine synthesis and metabolism, and the ontogenetic increase of the retinal dopamine level of rhesus monkey are reduced by light deprivation. PMID- 2577265 TI - Effects of CNQX, APB, PDA, and kynurenate on horizontal cells of the tiger salamander retina. AB - Effects of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 2-amino-4 phosphonobutyrate (APB), cis-2,3-piperidine dicarboxylic acid (PDA), and kynurenate (KYN) on the depolarizing actions of glutamate and kainate on horizontal cells (HCs) were studied in the larval tiger salamander retina. APB, PDA, and KYN hyperpolarized the HCs, but they failed to block either the actions of glutamate and kainate, or the HC light responses. APB and PDA did not cause membrane polarizations in either rods or cones, suggesting that the HC hyperpolarizations were not mediated by presynaptic actions of these compounds. CNQX, the newly synthesized non-NMDA (N-Methyl-D-Aspartate) receptor antagonist, blocked the HC light responses and the action of kainate, but not that of glutamate. These results suggest that the synaptic receptors in the tiger salamander HCs are probably non-NMDA although extra-synaptic NMDA receptors may exist in these cells. PMID- 2577267 TI - Darkness stimulates rapid synthesis and release of melatonin in rat retina. AB - The presence of melatonin in retina has been widely reported for over two decades although studies of its functional importance within the retina have only recently been emphasized. We have analyzed the biochemical characteristics of melatonin synthesis and release, focusing on rapid changes in response to light/dark conditions. Our major findings are consistent with the following conclusions: (1) melatonin synthesis is stimulated within minutes after exposure to darkness, and may reflect an increase in N-acetyl transferase activity; (2) melatonin is not stored, but rather it diffuses freely throughout the retina immediately after it is synthesized; and (3) the dark-induced increase in retinal melatonin release is a synthesis-coupled response and does not involve separate secretion mechanisms. The characteristics of melatonin synthesis and release described herein would be consistent with the proposed role of melatonin as a local paracrine effector of dark-adaptive responses in retina. PMID- 2577266 TI - Biochemical and physiological evidence that histamine is the transmitter of barnacle photoreceptors. AB - We tested the hypothesis that histamine is the transmitter released by barnacle photoreceptors. Median and lateral ocelli were incubated with 3H-histidine and found to synthesize 3H-histamine, identified by high-voltage electrophoresis. Synthesis could be blocked by the histidine decarboxylase inhibitor (S)-alpha fluoromethylhistidine. Histamine was applied to I-cells either by superfusion or by pressure ejection from a pipette (100 microM or 1 mM histamine) positioned close to the I-cell's soma. When bath-applied at concentrations ranging from 5 100 microM, histamine hyperpolarized the I-cell in a dose-dependent fashion and increased its conductance. At 100 microM, histamine abolished the I-cell's response to light. The response to a pulse of pressure-applied histamine was a hyperpolarization whose amplitude was graded with dose (determined by the duration of the pulse). This response persisted in concentrations of Co2+ and Cd2+ that blocked synaptic transmission from the photoreceptors. Cimetidine, an antagonist of mammalian H2 receptors, markedly decreased the cell's responses both to HA and to light at 100 microM and blocked both responses at 1 mM. Pyrilamine and triprolidine, H1 antagonists, had a complex effect on the I-cell's responses to histamine and to light. Neither H1 nor H2 antagonists, nor histamine itself, affected the voltage or light responses recorded in the presynaptic terminal region, or any phase of calcium-dependent action potentials induced in the terminal in the presence of tetraethylammonium ion. Thus, biochemical, immunocytochemical, and physiological evidence suggests that HA is the transmitter from these photoreceptors to the I-cells. Although gamma-aminobutyric acid (GABA) is also present in the photoreceptors, it did not affect the I-cell's responses to light or to histamine when bath-applied at 100 microM. Thus, GABA does not appear to modulate transmission from the photoreceptor to the I-cell. PMID- 2577268 TI - Pharmacological actions of peptides and indoleamines on turtle retinal ganglion cells. AB - In the turtle retina the peptides met-enkephalin (metENK), somatostatin (SS), neurotensin (NT), and the indoleamine serotonin (5-HT) modulate ganglion cell (GC) activity. The predominant action of the peptides is excitatory, generally enhancing spontaneous firing and light-evoked activity. In contrast, 5-HT usually inhibits these GC activities. MetENK has both direct synaptic input onto GC and indirect action possibly via a GABA inhibitory interneuron. The metENK actions appear mediated via a mu-opiate receptor; morphine and D-ala-metENK-amide (DALA), a stable analog of metENK, are agonists. Naloxone antagonizes the actions of metENK and its agonists. DALA occasionally inhibits GC. This inhibition is antagonized by picrotoxin, while concurrent excitatory action on GC is enhanced. DALA enhances GC response at high spatial frequencies; naloxone attenuates it. The enhancement by DALA suggests a narrowed receptive-field (RF) center, possibly due to changes in a GABA-mediated inhibitory surround. 5-HT inhibitory actions are also mediated via direct and indirect synaptic pathways. 5-methoxy-dimethyl tryptamine and methoxy-phenyl-piperazine are agonists of 5-HT action. They are both specific 5-HT1 agonists. LSD (lysergic acid diethylamide) and cyproheptadine, which act on 5-HT2 receptors, antagonize 5-HT actions in this retina. Strychnine enhances GC activity, probably by antagonizing glycine mediated inhibitory inputs. It does not block the inhibitory action of 5-HT, which suggests that the indirect 5-HT inhibition is not mediated via a glycinergic interneurone. 5-HT suppresses directional selectivity (DS) and attenuates high spatial frequencies in some GC. This may be mediated via inhibition of GABAergic amacrines subserving DS and the RF inhibitory surround. PMID- 2577269 TI - Cat-301 antibody selectively labels neurons in the Y-innervated laminae of the cat superior colliculus. AB - Cat-301 is a monoclonal antibody which recognizes a cell surface associated antigen of selected neurons in the central nervous system (CNS). In the visual system, cat-301 selectively labels Y-like cells in several visual structures, including portions of the lateral geniculate nucleus complex and visual cortex. The cat superior colliculus (SC) also receives Y input and contains cells driven by Y input which are selectively distributed in the deep superficial gray and deeper laminae. If cat-301 is selective to the Y-cell system in SC, labeled cells should be restricted to those laminae. To test this hypothesis, we have examined quantitatively the laminar distribution, percentage, size, and morphology of cells in SC labeled by the cat-301 antibody. Cat-301 labeled a variety of cells in the cat SC. Labeled cells were found within the deep portion of the superficial gray layer (6.6%), optic layer (27.6%), intermediate gray layer (26.9%), and the deep gray and white layers (38.5%). By contrast, only 2 of 667 labeled cells (0.3%) were found within that part of the upper superficial gray layer innervated exclusively by W input and thought to contain only W-driven cells. When considered as a percentage of the total cell population, cat-301 labeled cells represented less than 3% of cells in the superficial gray layer and approximately 15% in the deeper layers. Neurons labeled by cat-301 were all of medium to large size (mean average diameter = 33.3 microns; range = 15-84 microns) and included vertical fusiform and stellate cells in the upper layers and the very large neurons found in the intermediate gray and deeper layers. These results provide further evidence that the cat-301 antibody selectively recognizes the Y channel of the cat visual system. PMID- 2577271 TI - Molecular genetic analysis of tumors in von Recklinghausen neurofibromatosis: loss of heterozygosity for chromosome 17. AB - The most common inherited syndrome in man predisposing to neoplasia is neurofibromatosis-1 (von Recklinghausen disease) (NF1). We investigated the hypothesis that affected individuals carry a single inactive allele at the NF1 locus in the germline and that a tumor arises from a cell in a susceptible tissue in which the remaining normal allele has been lost or inactivated. DNA from tumor and nontumor tissue from 27 NF1 patients was analyzed with three markers closely linked to the NF1 locus and two additional markers from chromosome 17. No loss of heterozygosity was observed in neurofibromas, plexiform or not. For other tumor types analyzed, seven of 14 showed a loss. A loss of heterozygosity was observed in six of 11 of the malignant peripheral nerve tumors analyzed. Of the seven malignancies demonstrating a loss, five involved a neurofibrosarcoma. These findings suggest that the pathogenesis of neurofibrosarcoma in NF1 involves a deficiency of the NF1 gene product. In any given patient, loss of heterozygosity was detected at some marker loci but not others. Thus the mutations demonstrated in these tumors comprise a set of overlapping mutations, which may facilitate more precise localization of the NF1 gene. PMID- 2577270 TI - Neurotransmitters, receptors, and neuropeptides in the accessory optic system: an immunohistochemical survey in the pigeon (Columba livia). AB - Immunohistochemical techniques were used to survey the distribution of several conventional transmitters, receptors, and neuropeptides in the pigeon nucleus of the basal optic root (nBOR), a component of the accessory optic system. Amongst the conventional neurotransmitters/modulators, the most intense labeling of fibers/terminals within the nBOR was obtained with antisera directed against glutamic acid decarboxylase (GAD) and serotonin (5-HT). Moderately dense fiber plexuses were seen to label with antibodies directed against tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT). GAD-like immunoreactivity (GAD-LI) was found in many small and medium-sized perikarya within the nBOR. Some of the medium-sized cells were occasionally positive for ChAT-LI. Cell body and dendritic staining was also commonly seen with the two tested antisera against receptors-anti-GABA-A receptor and anti-nicotinic acetylcholine receptor. The antisera directed against various neuropeptides produced only fiber labeling within the nBOR. The densest fiber plexus staining was observed with antiserum against neuropeptide Y (NPY-LI), while intermediate fiber densities were seen for substance P (SP-LI) and cholecystokinin (CCK-LI). A few varicose fibers were labeled with antisera against neurotensin (NT), leucine-enkephalin (L-ENK), and the vasoactive intestinal polypeptide (VIP). Unilateral enucleation produced an almost complete elimination of TH-LI in the contralateral nBOR. SP-LI and CCK-LI were also decreased after enucleation. No apparent changes were seen for all other substances. These results indicate that a wide variety of chemically specific systems arborize within the nBOR. Three of the immunohistochemically defined fiber systems (TH-LI, SP-LI, and CCK-LI fibers) were reduced after removal of the retina, which may indicate the presence of these substances in retinal ganglion cells. In contrast, the fibers exhibiting ChAT-LI, GAD-LI, 5-HT LI, NPY-LI, NT-LI, L-ENK-LI, and VIP-LI appear to be of nonretinal origin. Two different populations of nBOR neurons exhibited GAD-LI and ChAT-LI. However, these two populations together constituted only about 20% of the nBOR neurons. PMID- 2577272 TI - Frequency and extent of allelic loss in the short arm of chromosome 3 in nonsmall cell lung cancer. AB - DNA was prepared from tumour and normal tissue from 48 patients representing all common histological types of nonsmall-cell lung cancer. Using eight DNA probes, which detect nine restriction enzyme fragment length polymorphisms (RFLP) on chromosome 3, we established that among the 44 informative patients 32 had lost alleles on the short arm of one of their copies of chromosome 3. Of these 32, at least 13 had also lost alleles on the long arm of chromosome 3, suggesting that the whole chromosome might be lost. For one patient, cytogenetic analysis indicated that the mechanism of allelic loss was reciprocal translocation followed by chromosomal loss of one of the reciprocal products. Two patients with allelic loss distal to the D3S3 locus (which maps to 3p13-14) retained heterozygosity at that locus. These results indicate that loss of alleles on the short arm of chromosome 3 is a common event in lung tumours of the nonsmall-cell type, that this loss occurs by a variety of chromosomal mechanisms, and that the minimally deleted region is 3p13-14----3pter. PMID- 2577273 TI - Dysphoric and depressive symptoms in chronic schizophrenia. AB - This study suggests that depressive symptoms are less common in severe, chronic, schizophrenic inpatients than would be predicted if these symptoms were manifestations of negative symptoms or drug-induced parkinsonism. The findings further suggest that depressive symptoms in such patients are independent phenomena which conform to a depressive syndrome. This depression does not represent a misidentification of the negative symptoms affective flattening and alogia, as measured by the SANS, or parkinsonism or akathisia. The study findings fail to support the view that long-term depot antipsychotic medication plays an important role in the genesis of depression and dysphoria in chronic schizophrenic patients. Depressive symptoms were found to occur as frequently, and dysphoria more frequently, in schizophrenic patients in the year after drug withdrawal compared with patients continuing on maintenance drug treatment for the same period. PMID- 2577274 TI - Strategies for linkage studies in schizophrenia. AB - Significant advances in linkage studies have occurred the past decade based on the use of polymorphic DNA markers known as restriction fragment length polymorphisms (RFLPs). This approach has led to the chromosomal localization of a number of important genetic diseases, and is being increasingly applied to schizophrenia. We discuss two strategies for performing linkage studies in schizophrenia, one based on methodical testing of the human genome, and the other based on selective use of markers. The selective approach uses data from the mode of transmission, previous linkage studies, cytogenetic studies, association studies, case reports, and candidate genes to identify markers that may have an increased likelihood for linkage. PMID- 2577275 TI - Medication effect on lymphocyte morphology in schizophrenia. AB - Past studies on the occurrence of atypical lymphocytes in the blood of individuals with schizophrenia are contradictory; some researchers have argued that such cells are a genetic marker of the disease while others have explained the cells simply as an effect of antipsychotic drugs. The present study blindly measured atypical lymphocytes in 14 schizophrenics on medication for at least 6 weeks and off medication for at least 4 weeks, ten Huntington's disease patients on antipsychotic medication, and ten normal controls. The patients with schizophrenia (P less than 0.05) and those with Huntington's disease (P less than 0.02) both had significantly more atypical lymphocytes than the normal controls. However no difference was found in the percentage of atypical lymphocytes in patients with schizophrenia on and off medication. The authors cite the need for studies of first-admission, never-tested patients to definitively settle this question. PMID- 2577276 TI - cDNA cloning of human calpastatin: sequence homology among human, pig, and rabbit calpastatins. AB - cDNA of human calpastatin, an inhibitor protein specific for calpain (EC 3.4.22.17; Ca2(+)-dependent cysteine proteinase) was isolated by screening of a library prepared from human liver mRNA with pig calpastatin cDNA fragment as a probe. The primary structure of human calpastatin was deduced from the nucleotide sequence of the cDNA and compared with that of pig and rabbit calpastatins already reported. Human calpastatin consisted of 673 amino acid residues and had 78% and 77% identity to pig or rabbit calpastatins, respectively. Human calpastatin had a domain structure with four internally repetitive sequences and one N-terminal non-homologous sequence like the other calpastatins. Human calpastatin had two deletions, 22 and 13 residues long in domain L and domain 1, respectively, compared to pig or rabbit calpastatins. PMID- 2577277 TI - NMR study of the interaction of beta-blockers with sonicated dimyristoylphosphatidylcholine liposomes in the presence of praseodymium cation. AB - The interaction of a series of beta-adrenoreceptor blocking agents with unilamellar dimyristoylphosphatidylcholine (DMPC) liposomes has been studied by proton nuclear magnetic resonance (1H-NMR) in the presence of praseodymium cation (Pr3+) at 30 degrees C. Addition of Pr3+ increased the splitting of the trimethylammonium group signals arising from the phospholipid molecules located at the internal and external surfaces of the bilayers. Adding Pr3+ caused a considerable downfield shift of the external peak but only a slight upfield shift of the internal peak (approximately 3%). The difference in chemical shift of the external and internal peaks (delta Hz) increased linearly as a function of Pr3+ concentration up to 10 mM. The addition of beta-blockers reversed the effect of Pr3+, and propranolol exerted the most pronounced effect, causing complete reversal of the splitting at a concentration of 5 mM. Much higher concentrations of other beta-blockers were required to displace Pr3+. A linear correlation between Pr3+ displacement (P) and logarithm of the apparent partition coefficient (K'm) in DMPC liposomes was obtained for hydrophobic beta-blockers, but hydrophilic beta-blockers did not fit this correlation. It appears that beta blockers that have ortho or meta substitution require penetration of the liposome bilayers before significant polar group interaction can occur. On the other hand, beta-blockers that have para substitution and low K'm values are able to interact with the polar surfaces of the liposomes without penetration to cause displacement of Pr3+. PMID- 2577278 TI - RFLP analysis of HLA-DR beta and -DQ beta genes in the Korean patients with insulin-dependent diabetes mellitus. AB - Human genomic DNA samples from 19 Korean patients and 31 controls of known serological DR antigen specificity were studied for insulin-dependent diabetes mellitus (IDDM)-associated variation in HLA-DR beta and -DQ beta restriction fragment length polymorphisms (RFLPs). Genotyping allowed for accurate assignment of HLA-DR types. For HLA-DRw6, a 12kb/DR beta/Taq I fragment was decreased in Korean IDDM (p less than 0.05). However, we could not find an increased frequency of a 12kb/DQ beta/Bam HI fragment or decreased frequency of a 3.7kb/DQ beta/Bam HI fragment in Korean IDDM. These results suggest a possible protective role of the HLA-DRw6 specificity in IDDM, irrespective of ethnic background, the absence of a specific DQ beta RFLP pattern associated with IDDM in Koreans, and the difference of the Korean population in the genetic of IDDM, compared to the Caucasoid population. PMID- 2577279 TI - [Uropathogenic Escherichia coli (UPEC) strains in Erzurum]. AB - In this study, urine-isolated microorganisms from urinary tract infections were generally evaluated, and among these microorganisms, 407 E. coli strains have been researched if they are uropathogenic E. coli (UPEC) by testing for the pilus formation and the hydrophobicity. We observed that 266 of the 407 E. coli strains have produced various types of pilus, and 250 of them have hydrophobic characteristics. PMID- 2577280 TI - Effect of beta-adrenergic blockade on hormonal responses during continuous and intermittent exercise. AB - The modifying effect on exercise performance and neuroendocrine response of the nonselective beta blocker timolol (10 mg b.i.d. for 5 days) and the beta 1 selective beta blocker metoprolol (100 mg b.i.d. for 5 days) was studied. The hormones studied were growth hormone, prolactin, cortisol, renin, epinephrine, dopamine, and norepinephrine. The response was studied during short-term maximal dynamic exercise, using two different exercise protocols; continuous (n = 11) and intermittent (n = 9) bicycle ergometry, in normal healthy young men. Accumulated work on placebo was nearly identical in the two studies, but was significantly reduced by 10.4% and 6.6% with timolol and by 4.7% and 6.7% with metoprolol, during continuous and intermittent exercise, respectively. During continuous exercise, accumulated work was 5.8% lower (p less than 0.05) with timolol than with metoprolol. The hormonal plasma concentrations of all hormones except renin were higher during continuous exercise than during intermittent exercise. Beta blockade had no effect on baseline hormonal levels, but the response was markedly changed during exercise. Maximum epinephrine, cortisol, and prolactin responses increased after beta blockade; dopamine remained nearly unchanged; while the renin responses were attenuated. Norepinephrine concentrations were slightly increased during continuous exercise by beta blockade and rose in direct proportion to the increase in workload. During intermittent exercise, maximum norepinephrine levels were significantly reduced by beta blockade compared with placebo. Thus the effect of beta 1-selective and nonselective beta receptor blockade on circulating hormones does not seem to explain the reduced exercise capacity following beta blockade. PMID- 2577281 TI - Myocardial, coronary, and peripheral effects of xamoterol (ICI 118,587) in open chest pigs. AB - The hemodynamic and coronary effects of increasing doses of xamoterol, a beta adrenoceptor partial agonist, were assessed in an anesthetized pig preparation in which cardiovascular reflexes were abolished and sympathetic tone was modified by infusion of noradrenaline (NA). Xamoterol, in basal conditions, increased heart rate (HR) from 104 +/- 12 to 120 +/- 13 beats/min (p less than .001); systolic, diastolic, and mean blood pressure, respectively, from 77 +/- 8 to 103 +/- 17 mmHg (p less than .01), from 48 +/- 7 to 70 +/- 12 mmHg (p less than .01), and from 58 +/- 7 to 84 +/- 14 mmHg (p less than .01); left ventricular dP/dT max from 2098 +/- 564 to 4205 +/- 937 mmHg/sec (p less than .001); and systemic vascular resistance (SVR) from 1745 +/- 564 to 2270 +/- 739 dynes sec cm-5 (p less than .01). The increase in HR and dP/dT max brought about by xamoterol was about 37% and 56%, respectively, of the maximum increase produced by NA. At the highest level of sympathetic tone, xamoterol reduced HR from 148 +/- 11 to 122 +/ 11 beats/min (p less than .001) and no significant change was observed in dP/dT max. The increase in blood pressure and SVR induced by xamoterol was maintained at each level of sympathetic tone. On the contrary, SVR did not change after NA, as expected, since receptors were fully blocked. For a given inotropic effect, xamoterol and NA produced a similar increase in coronary blood flow and myocardial O2 consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2577282 TI - Drugs interacting with alpha adrenoceptors. AB - Alpha adrenoceptors should be divided into various subtypes, comprising pre/postsynaptic and alpha 1/alpha 2-subpopulations, respectively. This classification implicates important functional differences between the various alpha-receptor subtypes, including certain differences in signal transduction following receptor stimulation. After a brief synopsis of the modern classification of alpha-adrenoceptors and its functional implications, the emphasis of the present survey is laid upon the various drugs that interact with the different alpha-adrenoceptor subtypes. Accordingly, agonists and antagonists towards alpha 1- and alpha 2-adrenoceptors are discussed with respect to the pharmacologic basis of their therapeutic activity. Some attention is paid to alpha 1-adrenoceptor antagonists with additional pharmacological activities, e.g., labetalol, ketanserin, and urapidil. Finally, the indirect and rather subtle interaction of calcium antagonists and ACE inhibitors with alpha adrenoceptor-triggered vasoconstriction is also dealt with, in particular with respect to the influence of these drugs on receptor-operated calcium channels and signal transduction following receptor stimulation. PMID- 2577283 TI - Digoxin and xamoterol in patients with moderate chronic heart failure. A double blind, randomized, controlled study. AB - Xamoterol is a partial beta 1 adrenoceptor agonist with positive inotropic properties. Treatment with xamoterol and digoxin was compared in 19 patients with cardiac failure (NYHA class II-III). The study consisted of a short-term and a long-term phase. The former was a randomized, double-blind, crossover study with 6-week treatment periods. In the 15 patients who completed this phase, there was no significant difference between exercise duration on digoxin and on xamoterol. Exercise duration increased on digoxin by 27% and on xamoterol by 17% relative to baseline. Comparing digoxin and xamoterol, maximum exercise heart rate (p less than 0.001), blood pressure (p less than 0.01), and the pressure-rate product during maximum exercise were significantly lower on xamoterol treatment. The systolic time interval was shorter on digoxin than on xamoterol (p less than 0.001). No changes occurred in the echocardiographic parameters. After the short term study, 13 patients were followed 3-6 months on the drug to which they had responded best (digoxin 7, xamoterol 6). The results of the short-term study were maintained during this period. In conclusion, we found that xamoterol may be an alternative to digoxin in patients with mild to moderate heart failure. PMID- 2577285 TI - Study of ridazolol on isolated canine and human coronary arteries. AB - Experiments were performed on isolated canine and human coronary arteries to study the alpha- and beta-adrenolytic properties of ridazolol. On canine coronary arteries precontracted with prostaglandin F2 alpha 2 microM and pretreated with phentolamine 1 microM, ridazolol competitively antagonized the isoproterenol induced relaxations, with a pA2 value of 8.5 (7.8-9.1). Thereafter the alpha adrenolytic activity of ridazolol was assessed on these same canine coronary vessels. Ridazolol activity was compared with that of prazosin on dose-response curves to norepinephrine in the presence of cocaine (30 microM) and propranolol (3 microM). Schild plots for both drugs gave straight lines, with slopes not different from unity. The pA2 value was 7.1 (6.8-7.3) for ridazolol and 8.1 (7.9 8.4) for prazosin. In another set of experiments the alpha-adrenolytic activity of ridazolol was compared on canine and human coronary arteries. A submaximal contraction with norepinephrine (10 microM) was first assessed in the presence of propranolol 3 microM. The addition of ridazolol 3 microM significantly decreased the norepinephrine (10 microM)-induced contractions of both preparations. However, the inhibition was more pronounced on canine coronary arteries. In conclusion, ridazolol is a potent beta-adrenergic antagonist with moderate alpha adrenolytic activity. The weaker inhibition of the norepinephrine-induced contraction observed in human preparations suggests the presence of a heterogeneous population of postjunctional alpha adrenoceptors. PMID- 2577286 TI - The costs of treatment of hypertension in Switzerland and worldwide. AB - Extrapolation from one country to another concerning costs of treatment of essential hypertension has to be made with caution because of wide variation of socio-economic differences and governmental price setting attitudes. The worldwide antihypertensive drug market shows a strong increase in the last few years and reflects the evolution away from diuretics and toward the more expensive ACE inhibitors and calcium antagonists, with a decreasing percent market of beta-blockers and absolute stagnation in other antihypertensives outside these four groups of drugs. PMID- 2577287 TI - Virgin and memory T cells have different requirements for activation via the CD2 molecule. AB - T cells can be divided into unprimed virgin (T0) and primed memory (T') subpopulations by their expression of different isoforms of the leukocyte common antigen. We have separated the CD4+ T cells into T0 and T' subpopulations and examined their capacity to respond to activation signals via the CD2 receptor molecule. On stimulation with a mitogenic combination of anti-CD2 antibodies, the T' population was induced to express IL-2 receptor, increased levels of the 4F2 antigen and to proliferate, whereas the response of the T0 populations was reflected solely by a minimal increase in the 4F2 antigen. The addition of IL-2 or monocytes to T0 cells stimulated with anti-CD2 antibodies did not enhance their expression of the IL-2 receptor or proliferation. However, T0 cells stimulated with the triad of anti-CD2 antibodies, monocytes, and IL-2 responded with high levels of IL-2 receptor expression and proliferation. The T0 subpopulation could also be induced to respond when cultured with anti-CD2 antibodies and phorbol myristate acetate. The results suggest that in order to respond to stimulation via the CD2 molecule, virgin T helper cells require additional signals that can be jointly provided by monocytes and IL-2. In contrast, memory T helper cells can be activated via CD2 signal transduction alone. PMID- 2577288 TI - CD2 expression in murine B cell lineage. AB - CD2 expression in murine B cell lineage was examined by flow cytometric and immunoprecipitation studies with anti-murine CD2 mAb and by Northern blot analysis. Cell surface expression of CD2 was demonstrated on all peripheral B cells and cell lines of B lineage. The murine CD2 transcript of 1.3 kb was detected in these B cells. An identical glycoprotein of 55-67 KD was precipitated from the lysates of surface radioiodinated thymocytes, splenic T and B cells, T and B lymphomas, RL male 1 and BCL-1, with anti-murine CD2 mAb. The majority of bone marrow B cells and a half of pre-B cells were found to be positive for CD2 expression. These results indicate that murine CD2 is expressed on B cell lineage at certain differentiation stages. PMID- 2577284 TI - Calcium channel antagonism and beta blockade in combination--a therapeutic alternative in cardiovascular disorders. A review. AB - Calcium-channel antagonists and beta-adrenergic blocking agents have become important modalities in the cardiovascular therapeutic armamentarium. These drugs are often administered as monotherapy to a wide range of cardiological patients with angina pectoris, hypertension, arrhythmias, congestive heart failure, and other diseases. Since within each class these drugs exhibit pharmacologic differences, it follows that their effectiveness varies in different disease states and that they exhibit a wide variety of side effects. In an attempt to optimize therapy, the individual drugs from these two classes can be combined; and the efficaciousness and side-effect profile of various combinations between calcium-channel antagonists and beta blockers are discussed in this review. Recommendations as to which patients may benefit from a combination and as to which patients may be harmed by the combination therapy will be made. Very few studies have compared the safety and efficacy of a single agent with the combination and with placebo in a controlled randomized fashion. To determine which therapy is superior and to determine which combination one should recommend under what circumstances, such placebo-controlled, randomized trials are a necessity, and will hopefully be performed although the complexity is enormous. PMID- 2577289 TI - Polymorphism of the human T cell receptor alpha chain variable genes: identification of a highly polymorphic V gene probe. AB - In this study, we report the RFLP of the human T cell receptor (TCR) alpha chain variable gene segments. Using DNA samples from 20 individuals and three restriction endonucleases (BamHI, EcoRI and HindIII), the degree of RFLP of a number of different V gene segments was defined. Half of the V alpha subfamilies (6/12) were characterized by a predominant hybridization pattern, with only a few individuals displaying a second pattern. However, one particular V gene family, V alpha 6, has at least five allelic forms that segregated consistently in familial studies. The V alpha polymorphisms revealed in this study, together with those exhibited by V beta gene subfamilies, should prove useful in studying possible associations between TCR gene usage and disorders of the immune system. PMID- 2577290 TI - Financing patient education in arthritis and musculoskeletal and skin diseases. PMID- 2577295 TI - Beta-blockade and calcium antagonism in practice. PMID- 2577291 TI - The use of long-acting neuroleptics in impala (Aepyceros melampus). AB - The long-acting neuroleptics perphenazine enanthate and pipothiazine palmitate were found to be effective for the long-term tranquilization of newly-captured and captive impala (Aepyceros melampus). Perphenazine enanthate (1.5 to 5.7 mg kg 1) produced a favourable state of tranquilization with a maximum effect lasting up to 7 d. Pipothiazine palmitate (4.5 mg kg-1) produced tranquilization lasting 16 d. The animals accepted humans inside their pens, at a distance of 0.5 to 4 m, without showing any excitement. No untoward side-effects were observed. PMID- 2577294 TI - Synthesis of 5-substituted 5-hydroxy-2-pyrrolidones, metabolites of the antipsychotic benzamide remoxipride. AB - This paper describes the synthesis of 5-[(3-bromo-2,6-dimethoxybenzamido)-methyl] 5-hydroxy-2-pyrrolidon e (3) and its 1-ethyl analogue 2, two urinary metabolites of the dopamine D-2 antagonist remoxipride [1, (S)-3-bromo-N-[(1-ethyl-2 pyrrolidinyl)methyl]-2, 6-dimethoxybenzamide]. Two synthetic schemes leading to a common intermediate, 5-benzamido-4-oxopentanoic acid 4, were developed. This key intermediate permits conversion into either metabolite. Reaction of 4 with isobutyl chloroformate furnished a mixed carbonic anhydride, which upon treatment with ethylamine or ammonia gave the 4-oxopentanamides 5 and 6, respectively. Ring closure afforded the corresponding 5-hydroxy-2-pyrrolidones 2 and 3. PMID- 2577292 TI - The use of long-acting neuroleptics, perphenazine enanthate and pipothiazine palmitate in two horses. AB - Two Arabian horse stallions with behavioural problems were treated with long acting neuroleptics in order to facilitate corrective training. Perphenazine enanthate, administered intramuscularly at a dose of 0.5 mg kg-1 had an effect for 30 d. Pipothiazine palmitate (1 mg kg-1) induced tranquilization of 30 d duration as well as extra-pyramidal clinical signs, ataxia and aphagia. Neither horse showed prolapse of the penis or haemolysis. PMID- 2577293 TI - Meeting report: thirteenth annual interdisciplinary cancer research workshop. PMID- 2577298 TI - Combination therapy with calcium-entry blockers and beta-adrenoceptor antagonists in hypertension. AB - The use of more than one drug to control blood pressure may be necessary in up to 50% of hypertensive patients seen in clinical practice. A rational basis for combination therapy includes 1) the use of drugs that act on different physiological systems involved in blood-pressure control and 2) using a second drug to counteract reflex responses, which may limit the effectiveness of the first, and, 3) as is less commonly practiced, the use of low doses of two drugs that act on the same or different physiological systems to avoid the side effects encountered with higher doses of single agents. The hemodynamic effects of calcium-entry blocking drugs and beta-adrenoceptor blockers are complementary and synergism might be anticipated, particularly with the dihydropyridines and beta blockers, since the latter prevent the short-term reflex increase in sympathetic activity occurring as a consequence of vasodilation. Although there are many studies advocating the benefits of such combinations, caution is required with combinations of beta-blockers and verapamil or diltiazem because of potential cardiac depressant effects resulting from the more complex effects of these calcium-channel blockers on cardiac myo-cytes and conducting tissue. Such problems would be more likely to be encountered in patients with long-standing hypertension and in whom poor left ventricular function and coro-nary artery disease may be present. PMID- 2577299 TI - [Clinical classification of traumatic dental injuries]. AB - In the world stomatological literature many more or less extensive clinical classification of posttraumatic damage to teeth are available. In the Polish stomatological school Ellis classification is used most frequently. However, this classification comprising nine classes of traumatic teeth damage is not sufficiently precise in the descriptions qualifying various classes. Moreover, the successive classes are not always logically arranged depending on the degree of damage. In view of this, the author has evolved another clinical classification of traumatic dental damage based on own clinical material and other classifications. The new classification is used in the Department of Developmental Age Stomatology in Zabrze. The base of the classification is the degree of damage to the dental tissues and the used therapeutic methods. Two-year experience with the classification showed that it is simple, sufficiently precise and easy for application by students and stomatologists. PMID- 2577297 TI - Beta-adrenoceptor antagonists plus nifedipine in the treatment of chronic stable angina pectoris. AB - The antianginal effects of beta-adrenoceptor antagonists are achieved by a reduction in myocardial oxygen demand. This is a rational approach to treatment in patients whose angina is caused by a fixed stenosis. However, dynamic coronary vasospasm is an important factor in patients with chronic stable angina. Nifedipine increases myocardial oxygen supply by reducing coronary vascular tone and is a logical approach to treatment in these patients. For monotherapy of angina, nifedipine is less effective than the beta-adrenoceptor antagonists, but the combination has additive effects in reducing the frequency of anginal episodes and improving exercise tolerance. Plasma concentrations of nifedipine are closely related to clinical efficacy, and the variable first-pass metabolism of the drug leads to wide interindividual differences in peak concentrations and duration of action. Increasing the size of individual doses of nifedipine carries a risk of enhanced side effects due to high peak plasma concentrations. Optimal treatment may be more appropriately achieved in some patients by a slow release formulation, but with an increased frequency of administration. PMID- 2577300 TI - Conceptual and methodological issues in studies of obsessive-compulsive and Tourette's disorders. AB - An association between recurrent motor and phonic tics and obsessive-compulsive behaviors has been noted since Tourette's Syndrome (TS) was first described. Obsessive-compulsive disorder (OCD) until recently was considered a rare disorder with poor prognosis. Currently, OCD is considered among the most common psychiatric diagnoses, and new treatments have spurred the development of considerable clinical, epidemiological, genetic, and biological research. Recent studies suggest a high rate of obsessive-compulsive symptoms in Tourette's Syndrome patients. A high rate of OCD among relatives of TS probands, both with and without OCD symptoms, suggest that some forms of OCD may represent an alternative expression of factors responsible for TS and/or chronic motor tics. Areas of conceptual controversy in the differentiation of tics, impulsions, and compulsions are discussed, confusing aspects of differential diagnosis are explored, and the relationship of diagnostic issues to clinical and familial studies are highlighted. There is considerable evidence for neuropsychiatric abnormalities in both OCD and TS; however, no studies have directly compared both disorders with similar methodological design. While studies of neurotransmitter function have primarily implicated dopaminergic dysfunction in TS and serotonergic function in OCD, other systems may be involved in each disorder, and neurotransmitter systems may be tightly linked, such that alterations of one system will affect other systems. This article reviews and discusses some of the conceptual and methodological issues associated with clinical, familial, neuropsychiatric and biological studies attempting to elucidate the association among tics, obsessive-compulsive disorder, and Tourette's Syndrome. PMID- 2577296 TI - Pharmacology of acute effort angina. AB - From the pharmacologic point of view, each of the major types of antianginal agents--calcium antagonists, beta-blockers, and nitrates--seem to act at least in part by an improvement of the myocardial blood supply. The recently elucidated mechanism of action of nitrates, acting on a common pathway with the endothelium derived relaxation factor (EDRF), suggests an important role for guanylate cyclase and cyclic GMP in maintaining coronary artery patency in patients with coronary atheroma. The efficacy of calcium antagonists, even in effort-induced angina, is in accord with a current hypothesis that physical exercise in the presence of coronary stenosis can cause relative coronary vasoconstriction, or at the least, failure of full dilation. Therefore, calcium antagonists all act, at least in part, on the "supply" side of the supply-demand equation. Beta adrenergic blockers appear to have as their major mode of action a reduction of heart rate, which not only reduces the oxygen demand but, through an anti ischemic effect, also appears to improve the endocardial blood supply (in relation to the heart rate). Thus beta-blockade indirectly enhances the supply side of the equation. The intriguing situation arises whereby all three major types of antianginal compounds may also act by a common mechanism of anginal relief, namely, improvement in the coronary blood supply, in addition to the diverse mechanisms specific to each type of compound. That conclusion does not mean the the "demand" side of the equation can be ignored. Rather, the critical importance of a reduced myocardial blood supply in the production of anginal syndromes is highlighted. PMID- 2577301 TI - Drug treatment of panic disorder--a critical review of controlled clinical trials. AB - The clinical efficacy of drug treatment for panic disorder has been evaluated in several studies, especially in the last decade. In this paper we reviewed double blind controlled clinical trials of antidepressants and benzodiazepines in the treatment of panic disorder. Tricyclic antidepressants (principally imipramine) and benzodiazepines were equally effective in reducing panic symptomatology. This evidence does not support the hypothesis that panic-related symptomatology is a psychopathological entity, requiring a specific antidepressant drug treatment. The combination of psychological therapy with drug treatment was associated with even better outcome. On the other hand, the efficacy of MAOI remains to be demonstrated. Better compliance with benzodiazepines may favor the clinical use of these drugs rather than antidepressants. However, more prospective controlled studies including follow-up examinations are required, in order to assess the risk/benefit ratio of these treatments after long-term therapy. PMID- 2577302 TI - Long-term stability of anorexia nervosa treatments: follow-up study of 218 patients. AB - We are reporting about the stability of n = 218 female in-patient treatments of Anorexia nervosa carried out at the University Clinic at Hamburg-Eppendorf from 1965 to 1979 mainly by a special program: introductory interview (with the family present), in-patient medical treatment (bed-rest, phenothiazines, tube-feeding), strict regimen and addressing the patients' conflict situation. The average interval between the end of therapy and the follow-up examination was 9.8 years. We were able to collect data about 93 per cent (n = 202) of the former patients concerning their somatic, psychological and psychosocial status. Based on these data we could assess 30 patients (14 per cent of our basic sample) as free of symptoms while 84 patients (39 per cent) presented slight symptoms so that 53 per cent of the former patients could exercise their profession without being considerably handicapped and able to keep up a relationship with a partner. On the other hand, 39 patients (18 per cent) still showed marked symptoms at follow up and with 19 patients (9 per cent) there were manifestations of severe or extreme symptoms. Thirty former patients (14 per cent) had died with the mortality rate distinctly increasing over the years. Possible interpretations of our results and consequences for therapy are presented. PMID- 2577303 TI - Genetic correction of hereditary disease. AB - Several hereditary disorders may be potentially correctable by the introduction and incorporation of the normal gene into human tissues using a variety of systems. Although technical issues surrounding integration, stable expression and potential insertional mutagenesis to the treated cells has not yet been fully resolved, enough scientific progress has already been made to consider somatic cell gene therapy acceptable from both the scientific and ethical viewpoints. Tissue-specific stem cell and embryonic stem cell transplantation will allow therapy earlier in the developing embryo. As technical problems are eliminated, these procedures will become morally permissible, as they will allow the correction of devastating hereditary disease. PMID- 2577305 TI - Challenging problems in peritoneal dialysis therapy. Abstracts of the IX Annual Conference on Peritoneal Dialysis. Dallas, Texas, February 23-25, 1989. PMID- 2577306 TI - Proceedings of the First Congress of the International Society of Ocular Toxicology. Toronto, Canada, June 1988. PMID- 2577304 TI - Prevention and treatment of fetal lung immaturity. AB - In the last 10 years the strategy for the prevention of neonatal respiratory distress syndrome (RDS) has been directed towards the acceleration of fetal lung maturity in utero by means of drugs administered to the mother, the most thoroughly investigated being glucocorticoids (GC), and to the development of surfactant substitutes for the treatment of surfactant deficiency at birth or following the development of RDS. GC decreases the incidence of RDS in the neonate delivered between 28 and 32 weeks and weighing less than 1,500 g. The type of GC and the drug-delivery interval are critical. Harmful potential side effects of GC have led to the testing of other drugs capable of accelerating fetal lung maturity, among which are ambroxol and aminophylline. Ambroxol has been shown to significantly reduce RDS compared to placebo without causing important adverse effects in either mother or baby. Our experimental studies on aminophylline have shown that the drug exerts only minor beneficial effects on fetal lung maturation and surfactant production. We have evaluated the association of GC with inositol. The sugar alcohol administered to the mother dramatically affected fetal lung mechanics, reducing GC adverse effects such as the decrease of lung protein content. More recently supplementary surfactant instilled into the trachea has been shown to improve oxygenation of premature babies and to reduce the severity of RDS. PMID- 2577307 TI - Drug-induced changes in dogs after long term application of a beta-blocker. AB - Ocular irritation studies are important in the safety evaluation of ocular formulations. There are many reports on acute ocular irritation studies, but almost nothing about prolonged ocular instillation of ophthalmic formulations. This report discusses the predominantly lymphocytic infiltrates seen in the limbus corneae and eyelids of dogs treated with 1 and 2% solutions of L-653,328, an ocular hypotensive beta-adrenoceptor antagonist, for up to 53 weeks. The number of animals affected and severity of the lesions increased with time and concentration. A minimal effect was seen microscopically with the 2% solution as early as 14 weeks. Rabbits treated similarly for 14 weeks had no such changes. The first and only clinical sign in dogs was diffuse pinkness of the bulbar conjunctiva seen from Drug Week 22 onwards. Although not seen with similar molecular structures, given the equivocal results in sensitization studies and the long time required for the development of change, delayed contact hypersensitivity was suspected as the cause of the ocular infiltrates. Simple chronic irritation was not ruled out, however. These findings suggest that delayed contact hypersensitivity in dogs may be a phenomenon not limited to skin, but may also involve the eye after repeated ocular instillation. PMID- 2577308 TI - Treatment of neuroleptic-induced akathisia with propranolol: a controlled replication study. AB - Twelve DSM-IIIR diagnosed schizophrenics, with neuroleptic-induced akathisia (NIA), were treated with either propranolol or matched placebo for two days, followed by a treatment crossover phase for five more days. Raters and patients were "blind" to treatment. This study shows that 120 mg of propranolol a day is more effective than placebo in reducing akathisia, and that propranolol's antiakathisic effect may require several days of treatment. PMID- 2577309 TI - Treatment of resistant schizophrenia with valproate and neuroleptic drugs. AB - Four cases of resistant Schizophrenia treated with valproate association with different neuroleptic drugs (thioridazine in three cases and loxapine in one) are presented. After a mean period of three months with this treatment, clinical improvement, consisting in a reduction of positive symptoms, as measured by the BPRS, and a normalization of hostile/disruptive behavior, was observed, and hospital discharge was possible. Reduction of symptoms was still present after a follow-up of 4 to 24 months. As valproate is a drug with gabaergic properties, a GABA involvement in the pathogenesis of schizophrenia is discussed. The association of valproate to neuroleptic drugs should be considered in the treatment of resistant Schizophrenia. PMID- 2577310 TI - [Extra-hormonal aspects of the central action of thyroliberin (TRH)]. PMID- 2577311 TI - [Contribution to the study and treatment of cryptorchism]. AB - Multiple series of undescended testes reported in the 1970's shown a significant decrease in spermatogonia content and tubular growth. After that most pediatric surgeons perform elective orchiopexy earlier. Pathologic studies in undescended testes shown significant complications. We studied 82 patients who were surgical treated between 1 to 13 years and we studied the tubular fertility index (TFI), mean of tubular diameter and Sertoli cells index (SCI). We found no correlation between age of patients and lesions. In our point of view the alterations of undescended testes is secondary to primary disease no to remain out of the scrotum. Current evidence suggests that the optimal time for performing orchiopexy is between four to seven years. PMID- 2577314 TI - Cell surface antigen Thy-1. Immunology, neurology, and therapeutic applications. PMID- 2577312 TI - The hemodynamic properties of amlodipine in anesthetised and conscious dogs: comparison with nitrendipine and influence of beta-adrenergic blockade. AB - The hemodynamic actions of the new dihydropyridine calcium-channel blocker amlodipine were assessed and compared with those of nitrendipine using anesthetised dogs and were also investigated in conscious dogs with and without beta-adrenergic blockade. After bolus intravenous administration, amlodipine (25 to 1600 micrograms/kg) or nitrendipine (1 to 128 micrograms/kg) was administered to anesthetised dogs at 30-minute intervals, caused dose-related reductions in systemic and coronary vascular resistances with corresponding increases in cardiac output and coronary flow. Nitrendipine, unlike amlodipine, caused marked acute hypotension. The onset of action of amlodipine was markedly slower than that of nitrendipine, and effects were maintained for 30 minutes--recovery from nitrendipine was largely complete at 30 minutes. In conscious dogs, amlodipine (250, 500, 1000 micrograms/kg IV) caused dose-related reductions in systemic vascular resistance that approached maximum within 5 minutes and persisted for over 4 hours. Reflex increases in heart rate, cardiac output, and cardiac contractility were attenuated by prior treatment with propranolol, resulting in earlier and greater falls in blood pressure, but no marked adverse effects on cardiac contraction or conduction. In the absence of propranolol, maximum falls in blood pressure occurred 3 to 4 hours after the dose, possibly as a result of the changed baroceptor sensitivity induced by amlodipine. These results show amlodipine to have the basic hemodynamic profile of other dihydropyridine calcium channel blockers, but in addition it demonstrates a slower onset and longer duration of action; the reasons behind these pharmacodynamic properties are discussed. PMID- 2577315 TI - Expression of Thy-1 in the nervous system of the rat and mouse. PMID- 2577317 TI - The human Thy-1 molecule. PMID- 2577316 TI - Rat Thy-1 antigen and its relation to RT-6. PMID- 2577318 TI - Distribution of Thy-1 in invertebrates and ectothermic vertebrates. PMID- 2577313 TI - Effects of cardiovascular disease on pharmacokinetics. AB - The pathophysiologic changes occurring in cardiovascular disease can affect the kinetics of drugs in several different ways. The present review examines these modifications and the underlying mechanisms. The kinetics of specific agents, such as antiarrhythmic, antihypertensive, cardiotonic, and other drugs are considered, and the clinical implications are outlined. The clinician should be aware of these modifications, because they require an adjustment of the dosage regimen. A rational basis for a correct therapeutic choice can be provided by adequate knowledge of these modifications. PMID- 2577319 TI - Cellular expression of the Thy-1 glycoprotein: analysis using interlineage hybrids, somatic cell mutants, and transfectants. PMID- 2577320 TI - Structural organization of the Thy-1 gene. PMID- 2577321 TI - Maturation of hematolymphoid cells that express Thy-1. PMID- 2577322 TI - The discovery of Thy-1 and its development. PMID- 2577323 TI - Genetic control of the immune response to the Thy-1 antigens--ten years later. PMID- 2577324 TI - The regulation of antibody responses to antigens of the cell surface: studies with Thy-1 and H-2 antigens. PMID- 2577325 TI - Relationship between the T-cell receptor-T3 complex and Thy-1. PMID- 2577326 TI - The structure of Thy-1 antigen. PMID- 2577327 TI - Treatment of murine lymphoma with anti-Thy-1.1 antibodies. PMID- 2577328 TI - Anti-Thy-1 in bone marrow transplantation. PMID- 2577329 TI - Treatment of autoimmune disease with monoclonal anti-CD4 antibodies. PMID- 2577330 TI - The function of Thy-1. PMID- 2577331 TI - Anchoring of Thy-1 to the cell membrane. PMID- 2577333 TI - Determination of pipothiazine in human plasma by reversed-phase high-performance liquid chromatography. AB - A method is described for the determination of pipothiazine in human plasma, based on reversed-phase HPLC. The method has been applied in a pharmacokinetic study of pipothiazine in six psychiatric patients receiving repeated depot intramuscular injections for six months. A number of compounds likely to be taken concurrently by patients were tested for potential to interfere with the assay. There was no evidence of "dose-dumping" in the period following injection. Comparison of the pharmacokinetic profiles after the first and sixth injections showed no evidence of drug accumulation. PMID- 2577334 TI - Genetic basis for carcinogenesis. Tumor suppressor genes and oncogenes. PMID- 2577332 TI - Characterization of Thy-1 with monoclonal antibodies and evidence of Thy-3. PMID- 2577335 TI - Nakahara memorial lecture. Hereditary cancer, oncogenes, and anti-oncogenes. AB - Dominantly heritable predisposition to cancer is well known, even if rare. Such heritable cases are known for most cancers. Predisposition is usually to one or a few specific cancers, and the kinds of pedigrees that are found suggest the existence of an array of 50 or so such cancer genes. Penetrance is usually high, as is the relative risk for a particular tumor. The inherited event is insufficient to cause cancer; at least one other (somatic) event must occur. For one tumor, retinoblastoma, the total number of necessary events seems to be two for both the hereditary and non-hereditary forms, and those events involve mutation or loss of the two copies of a tumor suppressor gene on chromosome 13. Analyses of tumors with polymorphic syntenic DNA probes and for abnormality of the gene itself have provided a picture of the kinds of first and second events that can occur. Several other tumors may follow the retinoblastoma scenario, including tumors associated with multiple endocrine neoplasia type 1 and with neurofibromatosis type 2, and identify the loci of several other putative anti oncogenes. Still other hereditary cancer genes have been mapped, but evidence that they are suppressor genes is incomplete. It is possible that the inherited mutation may sometimes occur in an oncogene, although no such cases have been validated. In most, perhaps all, tumors, further genetic changes occur. In some instances these appear to be in oncogenes, and sometimes in anti-oncogenes. Some of these events appear to play a role similar to that of promotion in experimental carcinogenesis, whereas others are clearly important in progression. The process is particularly complicated in some of the common carcinomas, where changes in both oncogenes and anti-oncogenes are common. PMID- 2577336 TI - The evidence for human tumor suppressor genes. AB - The evidence for human tumor suppressor genes is reviewed. Initial evidence was provided by somatic cell hybridization, where somatic cell hybrids derived from the fusion of malignant and normal parental cells were found to be transformed but nontumorigenic. Tumorigenic segregants appeared at later intervals and were associated with the loss of specific normal chromosomes. Evidence for loss of tumor suppressor genes in many human malignancies was provided by a combination of cytogenetic and restriction fragment length polymorphism analyses. Functional analyses, using monochromosome transfer from normal cells into cancer cells, have confirmed the existence of suppressor genes and their critical role in control of tumor formation. Recently, the tumor suppressor gene Rb-1 has been cloned and also shown to have tumor-suppressing properties. Most recently, a candidate tumor suppressor gene on chromosome 17 (p53) has been implicated in colorectal carcinomas and other human malignancies. It is of interest to note that this gene was originally described as an oncogene. The biological mechanism of tumor suppression has been linked to the induction of differentiation in both somatic cell hybrids and osteosarcoma cells transfected with the normal Rb-1 gene. However, recent studies with monochromosome transfer into neuroblastoma cells indicates that differentiation may be dissociated from tumor suppression. Tumor suppressor genes do not act directly as negative regulators of conventional "dominantly-acting" oncogenes and therefore cannot be considered as anti oncogenes in the sense of directly interacting with and regulating the expression of such oncogenes as ras and myc. However, it is speculated that they may negatively regulate an, as yet undiscovered, family of oncogenes which would not be dominantly expressed. PMID- 2577337 TI - Multiple genetic alterations in small-cell lung carcinoma. AB - By restriction fragment length polymorphism (RFLP) analysis, it was found that loss of heterozygosity (LOH) at three different chromosomal loci, 3p, 13q, and 17p, occurs simultaneously in nearly 100% of small-cell lung carcinomas (SCLC). This was observed even in stage I tumors and an untreated tumor, and it occurred prior to NMYC amplification. The common region of LOH on chromosome 3p was 3p14 24.1, and this region was also frequently lost in carcinoma of the uterine cervix (100% at D3S2 on 3p14-21) as well as renal cell carcinoma (56% at ERBA beta on 3p22-24.1), suggesting the presence of tumor suppressor gene(s) for these cancers in this region. On chromosome 13, LOH was observed commonly in the region between 13q12 and 13q22, including the RB locus on 13q14, and normal RB protein was not detected in any of 9 SCLC cell lines by immunoprecipitation analysis. The common region of LOH on chromosome 17 was 17p13 and is the same as that in colon carcinoma and osteogenic sarcoma. Since LOH is supposed to unmask the recessive mutation of tumor suppressor gene in the remaining allele, these results may imply that at least six genetic alterations are necessary to convert a normal cell into a fully malignant cancer cell in SCLC. RFLP analysis was performed on several other types of human cancers, including carcinoma of the uterine cervix, neuroblastoma, hepatocellular carcinoma, pheochromocytoma, and stomach cancer to determine the chromosomal loci of putative tumor suppressor genes in each tumor. Chromosomal loci showing frequent LOH were different among these tumors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2577338 TI - Regulation of expression and transforming ability of the c-erbB-2 gene. AB - The human c-erbB-2 gene encodes a growth factor receptor-like protein that is highly homologous to the epidermal growth factor (EGF) receptor. Previous studies have shown that the c-erbB-2 gene is preferentially expressed in fetal epithelial cells, suggesting that the ligand of the gene product controls the growth of these cells. Molecular analysis of the c-erbB-2 promoter region revealed three regulatory systems: they are a typical set of CCAAT and TATA boxes, GC boxes, and Myb binding sites. Binding of the c-myb and B-myb gene products to the promoter region seems to down-regulate the c-erbB-2 mRNA synthesis. Elevated expression of this gene is often associated with adenocarcinomas such as breast cancers and stomach cancers and is correlated with the spread of the former. Involvement of the c-erbB-2 gene in the tumor development is further demonstrated by induction of B-lymphomas in transgenic mice carrying normal or mutated forms of this c-erbB 2 gene. In addition, the transforming potential of the c-erbB-2 gene is closely correlated with elevated tyrosine kinase activity of the gene product, which is negatively regulated by its carboxy-terminal sequence of about 230 amino acid residues. PMID- 2577339 TI - [Study of the relations between small cell lung cancer and the APUd system based on the analysis of clinical, biological and molecular-genetic properties]. AB - The paper presents the latest opinions dealing with biological features (the hormone production) and histogenesis of the small cell lung cancer (SCLC). The authors try to explain the problem of the rapid progression of SCLC as well as the rapid insensitivity to radiation and chemotherapy following initial responsiveness of SCLC. PMID- 2577340 TI - [Working hypothesis for the pharmacologic research in the glutamatergic approach to Alzheimer's disease]. PMID- 2577341 TI - [Pharmacologic effects of glycerolformal on the central nervous system]. AB - Glycerolformal is not devoid of action on mice psychomotor behaviour. Administered through the digestive tract with infralethal doses, it can exercice depressing effects on muscular strength and sensitivity to pain without affecting inquisitiveness. It opposes the stimulating effects specific to pentetrazol, amphetamine and apomorphine and is a protection against electric convulsions but tends to increase the toxicity of tryptamine. PMID- 2577342 TI - Molecular recognition: Its role in chemistry and biochemistry. Sopron, Hungary 24 27 August 1988. PMID- 2577343 TI - Telling the players without a scorecard. Gene Cascades and Second Messengers in Cancer Sponsored by the Research Institute of Molecular Pathology, Vienna, Austria, May 20-22, 1989. PMID- 2577344 TI - Coping with stress. International Workshop on Genetic Response to Environmental Adversity sponsored by the National Institute of Child Health and Human Development, Airlie, VA, USA April 23-26, 1989. PMID- 2577345 TI - Busy signals. Intercellular Communication in Growth and Development Sponsored by the Fogarty International Center and the National Institutes of Health, Bethesda, MD, USA, May 15-17, 1989. PMID- 2577346 TI - Mouse versions of fly developmental control genes: legitimate or illegitimate relatives? AB - Embryo development requires a complex order of events that must occur at the correct time and in the correct space. A series of decisions takes place as cells divide and become committed to increasingly specialized and limited domains of the embryo. Many genes that are important in orchestrating this process were originally identified in the fruitfly Drosophila melanogaster. Conserved sequences from the fly genes have been used to clone homologous genes in vertebrates, including mice. Studies of the pattern of expression of these genes during murine development in conjunction with the use of new functional assays suggest that not only DNA sequences, but also functional roles during embryogenesis, have been conserved. Thus, we may have the tools in hand to begin to understand how vertebrate development and cell differentiation take place. PMID- 2577347 TI - The natural history of HIV infection. PMID- 2577348 TI - Recent advances in clinical management. PMID- 2577350 TI - Health education. PMID- 2577349 TI - AIDS counselling. PMID- 2577351 TI - Worried well and psychological issues. PMID- 2577352 TI - African contributions on AIDS/HIV. PMID- 2577353 TI - Progress for developing countries. PMID- 2577354 TI - Neuropsychiatry of AIDS. PMID- 2577355 TI - AIDS and drugs. PMID- 2577356 TI - HIV and haemophilia. PMID- 2577357 TI - The economic impact of AIDS. PMID- 2577358 TI - AIDS and women. PMID- 2577359 TI - Correlations between age and rat dermis modifications. Ultrastructural morphometric evaluations and lysyl oxidase activity. AB - The extracellular matrix is a complex, integrated macromolecular system which plays a crucial role in the economy of each organ. In this study we focused our attention on the correlations between age and rat skin dermis. The latter was chosen as a model of the connective tissue, and was analyzed by means of electron microscopy and by measurement of the activity of lysyl oxidase, the enzyme involved in collagen and elastin crosslink formation. Ultrastructural and morphometric evaluations associated to body weight growth, showed a progressive increase in the amounts of extracellular components and a progressive reduction in the cell density. Skin from adult animals appeared characterized by a well organized matrix; by contrast, in old rats, we observed several degenerative features such as the disorganization of collagen bundles, the vacuolization of elastic fibers, and the atrophy of the mesenchimal cells. Morphometric evaluations in old animals showed a slight but significant reduction in the percentage of the total collagen measured, a fair stability in the area occupied by the elastin fibers, and an increase of the apparently non-structured matrix. The fact that lysyl oxidase activity was diminished in old rats does not corroborate the observation by several authors that increased collagen insolubility is a consequence of higher intra- and intermolecular crosslinking. This would suggest that other chemical modifications, such as crosslink oxidation or non enzymatic glycosylation, might be involved during the aging of connective tissue. The qualitative and quantitative modifications observed at all ages illustrate the correlation between connective tissue modifications and structural and/or functional properties of the skin. PMID- 2577361 TI - Hemorrhagic fever with renal syndrome: separation of human peripheral blood T and B cells and detection of viral antigen. AB - Total lymphocytes in peripheral blood were prepared from patients with hemorrhagic fever with renal syndrome by a density gradient on Ficoll-Hypaque, and then T and B cells purified by passing the lymphocytes over a nylon column with modifications. Also, after modification of cell fixation and use of a spinner for smear drying, the number of cells were increased and the duration for slide preparation was shortened, thus resulting in quality slides. Detection of viral antigen by immunofluorescence assay using monoclonal antibodies to Hantavirus (HTNV) showed that the total lymphocytes, T cells and B cells were infected with HTNV during the early stages of the illness and no specific fluorescence was seen in the cells from the late diuretic phase to convalescent phase. PMID- 2577360 TI - Peritoneal functional parameters after five years on continuous ambulatory peritoneal dialysis (CAPD): the effect of late peritonitis. AB - Functional stability of the peritoneum is essential for patients on long-term continuous ambulatory peritoneal dialysis (CAPD) treatment. Sixteen patients on CAPD treatment for at least 4 years were studied. Their mean age was 47 +/- 15 years, 5 were males, and none were diabetic. Residual creatinine clearance at the beginning was 2.1 +/- 2.6 mL/min. Once yearly since starting CAPD, we have evaluated their peritoneal ultrafiltration (UF) and diffusion capacities by calculating the peritoneal mass transfer coefficient (MTC, mL/min) for urea and creatinine. Patients were categorized so that we could distinguish the effect of peritonitis, betablockers, and hypertension. For all patients the average initial and final MTCs and UF values were not different. Early episodes of peritonitis (those occurring less than 36 months after starting CAPD) did not influence long term function. However, late peritonitis (occurring greater than 36 months since initiation) induced a decrease in urea-MTC (22.3 +/- 6 to 15.8 +/- 3.9, p less than 0.05), creatinine-MTC (9.4 +/- 3.1 to 7.4 +/- 2.5, p less than 0.05), and a corresponding increase in UF (1.25 +/- 0.4 to 1.4 +/- 0.3, mL/min, p less than 0.05). Age, sex, betablockers and hypertension did not influence the peritoneal parameters followed. After 5 years on CAPD, functional stability of the peritoneum is evident, except for patients who suffer late episodes of peritonitis. We speculate that the peritoneum in patients who have been on long term CAPD are more susceptible to injuries, such as peritonitis, and that this results in functional deterioration. PMID- 2577362 TI - Molecular genetic variation in the centromeric region of the X chromosome in three Drosophila ananassae populations. II. The Om(1D) locus. AB - Restriction-site and sequence-length polymorphism in the Om(1D) locus region on the X chromosome in Drosophila ananassae was investigated for three natural populations (from Burma, India, and Brazil), by using hexanucleotide-recognizing restriction enzymes. The estimates of average heterozygosity per nucleotide (pi) were 0.0085, 0.0043, and 0.0004 for the Burma, India, and Brazil populations, respectively, and the average frequencies of insertions/deletions were 0.078, 0.054, and 0.007/chromosome/kb. While the pi values at this locus are similar to the estimates obtained from other euchromatic loci in D. ananassae or in other Drosophila species, the frequencies of insertions/deletions are much higher than those previously reported from Drosophila. The exceptionally high frequencies of length polymorphisms in the Burmese sample and, to a lesser extent, in the Indian sample indicate that the hypermutability of Om(1D), caused by the frequent insertion of the transposable element tom, may be due to locus-specific rather than to tom element-specific properties. The low level of nucleotide variation in the Brazilian population seems to be due to a recent bottleneck of population size. This population was apparently founded in recent years by a small number of individuals and has been relatively isolated ever since. PMID- 2577363 TI - [Hiccup: towards the (re)discovery of an often neglected sign]. PMID- 2577364 TI - [Periarteritis nodosa with heart valve disease disclosed by occlusion of the central artery of the retina]. AB - We report a case of periarteritis nodosa revealed by blindness due to occlusion of the central retinal artery. The disease appeared after a serous otitis and was accompanied by thrombocytosis. Its outcome was favourable under corticosteroid therapy, but it was complicated by aortic valve regurgitation. Lesions of fibrinoid necrosis were found on the aortic cusps removed during surgical replacement. It seems highly probable that the ocular and valvular lesions were specific, although this cannot be directly demonstrated. The case presented here is exceptional, and the relevant literature is reviewed. PMID- 2577365 TI - Clinical significance of HIV-2 infection in West Africa. PMID- 2577366 TI - Out of control. Molecular Aspects of Growth Control sponsored by the Japanese Cancer Association and the American Association for Cancer Research, Honolulu, HI, USA, May 28-31, 1989. PMID- 2577367 TI - The company they keep. Fifth Annual Meeting on Oncogenes sponsored by the Foundation for Advanced Cancer Studies, Inc., Frederick, MD, USA, June 27-July 1, 1989. PMID- 2577368 TI - Depression to ecstasy. The Neuropharmacology of Serotonin sponsored by the New York Academy of Sciences, New York, NY, USA, July 10-13, 1989. PMID- 2577369 TI - Evidence for a single glutamate receptor of the ionotropic kainate/quisqualate type. AB - The kainate (KA) and the quisqualate (QUIS) receptors that activate cation channels in the central nervous system have previously been defined as two of the major glutamate receptor types. In amphibian brain, an exceptionally rich source of these sites, they can be coextracted by octylglucoside and shown to behave as one entity in all analyses made in solution. When partly purified by lectin affinity, ion-exchange chromatography or by sucrose gradient centrifugation, the two activities comigrate in a 1:1 ratio. When the QUIS component is bound to an immobilized specific QUIS agonist, the KA component is extracted in parallel with it. There are equivalent numbers of the QUIS and KA sites and the two sites show a single affinity series for the binding of glutamatergic agonists. We deduce that KA or QUIS select different conformations of a single KA/QUIS receptor binding site, leading thus to the different channel-opening events that have been reported for these two agonists. PMID- 2577371 TI - [Modulators of multidrug resistance in neoplastic cells]. PMID- 2577370 TI - [Multidrug resistance of neoplastic cells--facts and hypotheses]. PMID- 2577372 TI - What is your experience in the use of beta-blockers post radial keratotomy in cases of overcorrection? PMID- 2577373 TI - First International Conference on Confocal Microscopy and the Second International Conference on 3-D Image Processing in Microscopy. March 15-17, 1989. Academisch Medisch Centerm, in Amsterdam, The Netherlands. PMID- 2577374 TI - A graphical representation of the electrostatic potential and electric field on a molecular surface. AB - The graphics program presented, ARCHEM, draws the molecular electrostatic potential (MEP) on a molecular surface color-coded according to the magnitude of the potential. Vectors can be drawn on the surface to show the electric field surrounding the molecule and color-coded according to the magnitude of the field. The electrostatic potential (ESP) calculated from the wave function or from net atomic charges using GAUSSIAN 80 UCSF1.2 can be plotted at points on a shell surrounding the molecule. For the neurotransmitter glycine zwitterion, the MEP is calculated from the wave function and from different point charge models, and the results are represented graphically. PMID- 2577375 TI - Elevated plasma glutamate concentrations in HIV-1-infected patients may contribute to loss of macrophage and lymphocyte functions. AB - We tested the hypothesis that the loss of immunological reactivity in HIV-1 infected persons may result partly from a virus-induced metabolic disorder. Patients who are infected with the acquired immunodeficiency syndrome (AIDS) associated human immunodeficiency virus 1 were found to have, on average, markedly elevated and highly variable plasma glutamate concentrations. A similar elevation of the extracellular glutamate concentration was found to inhibit DNA synthesis in cultures of mitogenically stimulated lymphocytes. An even stronger inhibition was seen with the structural analogue quisqualate, and a moderate inhibition was seen with N-methyl-D-aspartate and kainate, i.e. with well established pharmacological probes for the excitatory glutamate receptors in the vertebrate central nervous system. The inhibitory effect of glutamate was compensated by adding cysteine or relatively large numbers of 'splenic adherent cells' to the culture. Elevated extracellular glutamate levels were also found to reduce the capacity of murine macrophages, human blood monocytes, and murine fibroblastoid cells (L929 cells) to release acid-soluble thiol (cysteine) into the extracellular space. The three cell types differed, however, with respect to their sensitivity against the three structural analogues of glutamate. The elevated glutamate concentration was not non-specifically toxic for cultured macrophages, since glycolytic activity and arginase activity were not inhibited. Implications of these observations for the pathogenetic mechanism of AIDS are discussed. PMID- 2577376 TI - CD4-, CD8- gamma/delta cells from normal mice respond to a syngeneic B cell lymphoma and can induce its differentiation. AB - Lymph nodes and spleens from normal unimmunized mice contain small numbers of CD3+, CD4-, CD8- (double negative, DN) T cells. Of these, approximately one-third express the marker Ly-5(B220) in a form previously seen only on normal B cells and a population of DN T cells found in mice genetically prone to develop autoimmunity. DN T cells proliferate when co-cultured with a syngeneic surface Ig+ lymphoma, CH12. After one cycle of stimulation with CH12 almost all of the responding CD3+ DN cells express Ly-5(B220), suggesting that it is an activation marker for some DN T cells. The CH12 responding population also contains cells with two other phenotypes, Thy-1+, CD4-, CD8-, Ly-5(B220)+, sIgM-, CD3- and Thy 1+, CD4+, CD8-, Ly-5(B220)-, sIgM-, CD3+. The Ly-5(B220)+, CD3- population is no longer found after repeated stimulation. While the relationship between these three populations is unknown, DN T cells can proliferate in the absence of CD4+ or CD8+ cells and therefore their proliferation is not dependent on the presence of other T cells or lymphokines produced by CD4+ or CD8+ T cells. Anti-CD3 immunoprecipitation of CH12-responding cells reveals at least seven different receptor proteins of which five can also be precipitated with an anti-(C gamma 1/C gamma 2) monoclonal antibody. Thus at least three different TCR gamma-delta heterodimers are expressed by CH12-responding T cells. The Thy-1+, CD4-, CD8-, Ly 5(B220)+ cells can provide help to CH12 cells for Ig secretion even in the absence of the nominal antigen for the B lymphoma cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2577377 TI - A double-blind placebo-controlled study of the efficacy and tolerability of ebastine against hayfever in general practice patients. AB - Ebastine is an H1 antihistamine. Using a double-blind, parallel group randomized study design, the efficacy and the tolerability of oral ebastine (10 mg daily escalating to 40 mg daily according to clinical need) was compared over 4 weeks during 1986 with matching placebo in 40 general practice patients suffering from hayfever. Ebastine (19 patients) was more effective (P less than 0.05) than placebo (21 patients) against symptoms of running nose, itching nose, sneezing and blocked nose. Ebastine was superior to placebo in respect of the total symptom score as well as when judged by the investigators' and the patients' opinion of overall efficacy. Ebastine caused few adverse events, none of which resulted in a patient being withdrawn from treatment. Significantly more patients were withdrawn because of inefficacy from the placebo (n = 12) than from the ebastine (n = 3) treatment group (P less than 0.02). It is concluded that ebastine (10-40 mg daily) is an effective and well tolerated treatment for hayfever. PMID- 2577378 TI - Inhibition of aminopeptidase M by alkyl D-cysteinates. AB - Ethyl D-cysteinate is a potent competitive inhibitor (Ki = 3.5 x 10(-7) M) of aminopeptidase M. D-cysteine and ethyl L-cysteinate inhibit more than two orders of magnitude less effectively. Inhibition studies on several n-alkyl esters of D cysteine reveal an optimum at the n-butyl ester (Ki = 1.8 x 10(-7) M). The results are consistent with the hypothesis that the thiol group coordinates to Zn+2 at the active site and the alkyl group occupies the hydrophobic binding site for the side chain of the amino-terminal residue of substrates. Cytosolic leucine aminopeptidase is not significantly inhibited by ethyl D-cysteinate. PMID- 2577381 TI - [32d Fall Congress of the Japanese Society of Periodontal Disease, October 5-6, 1989 at Kurashiki. Abstracts]. PMID- 2577379 TI - [Follow-up investigation of the effect of Ca(OH)2 on the teeth with necrotic pulps and immature root development and surrounding periodontal tissues]. AB - In this study Ca(OH)2 + distilled water was applied to the traumatized necrotic incisor teeth with immature root development. After necessary mechanical and chemical root canal disinfection the paste was applied to 13 teeth of 9 patients. Periodontologic problems in vestibule gingiva of the teeth prior to the treatment doubted if the primary lesion was the necrotic pulp or periodontal infection. After control periods (6 weeks, 3 months, 6,9,12,18,24 months) the cases were evaluated roentgenographically whether the apical closure was obtained. After observation of calcified tissue in the apex the canals were filled with sectioned warm gutta percha with vertical condensation. All the cases were successful except one and after treatment restorations were performed. In case all the patients experienced periodontologic problems from the teeth prior to treatment, after endodontic treatments and application of Ca(OH)2 to the canal, healing of periodontal tissues were also observed. This finding shows the importance of differential diagnose of periodontal problems caused by pulpal necrosis. PMID- 2577380 TI - Proceedings of the HIV and Work Environment Congress. Pavia, November 25, 1989. PMID- 2577382 TI - Immunological differences between squamous cell cancer patients treated with and without biological response modifier (OK-432): evaluation at a period of more than one year after the last treatment. AB - The cellular immunity of peripheral blood was analyzed to evaluate the efficacy of OK-432 between 3 groups of patients with oromaxillary squamous cell cancer, which were composed of 14 patients in the pretreatment stage, 8 patients who were free from cancer more than one year after the last cancer therapy and had been continuously treated with OK-432, and 14 patients who had undertaken cancer therapy without OK-432 and were also free from cancer for at least one year. As parameters of cellular immunity, leucocyte counts, percent composition of T cells, percent compositions of T-lymphocyte subsets (OKIal+, OKT3+, OKT4+, and OKT8+) and the ratio of OKT4+ and OKT8+, PPD skin test, and lymphocytic blastogenesis induced by PHA and Con-A, were examined. The results showed no significant difference between the patients treated with and without OK-432. Nor was there any significant difference between the pretreatment group and the posttreatment groups with and without OK-432 treatments in any of the examined immunologic parameters. PMID- 2577383 TI - [Displacement and distortion of non-precious ceramometal fixed bridges during the laboratory procedure. Non-precious metal]. AB - The purpose of this study is to measure the three-dimentional displacement and distortion in the Non-precious (Ni-Cr) ceramometal bridges during laboratory procedure. At the time of pre-soldering stage, the author examined the phosphatic investment (low and high thermal expantion: ph, ps) to addition of gypsum investment which was usually to used to fix the position for soldering. The following results were obtained. 1. The displacement of the framework at the pre soldering stage, in case of using phosphatic investment mixed by water (ph), it was small on the horizontal and vertical plane. And in the other case of mixing by 100% colloidal silica (ps), a kind of displacement was seen where the curve of the bridge opened as result of the position of two soldering bodies getting out of order from each other. So that phosphatic bonded investment, it can be used to because thermal expantion can be controlled, the soldering block. 2. Throughout the surface grinding of framework to grazing, displacement was minimal, at the time of opaque porcerain firing, the curve of the bridge closed but it had no effect on clinical adaptation. 3. In the case of assembling multi-unit non precious ceramometal bridge mainly the displacement caused at pre-soldering stage, so it is important to check the adaptation after soldering. PMID- 2577384 TI - [Traumatic injuries to the teeth for children]. AB - For modern medical care, social background may be an essential factor, and medical care through out the individual's life time appears to have significant meaning. From this point of view, total dental care throughout childhood is being carried out in the field of pediatric dentistry. It can be stated that we pedodontists have a degree of farsight in the treatment of traumatic injuries to the teeth regarding children (the theme of the lecture), since the injured teeth are treated not only as items to be restored but also as a part of the growing body with careful consideration on the effects with regard to orlo-facial growth. It is obvious that epidemiological surveilance is necessary to understand the cause of dental injuries, and also careful attention ought to be paid to the activity of the children to grasp the potential background of dental trauma. Here, I would like to explain the consequences of the serial work on the traumatic injuries to teeth which were carried out in our department. 1) The prevalence of dental injuries in children appeares to be on the increase according to a judgement based on the surveilances form in and out of the country. Also as the parental recognition for dental injuries became higher, more patients visited dental clinic or hospital looking for improved treatment techniques. 2) Careful consideration must be paid to the succedaneus permanent tooth germ, when a deciduous tooth suffered from traumatic injury. The effect of the direction applied and the area of the traumatic force on the root of the deciduous tooth, the successor and the surrounding tissue was investigated by means of kinetic analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2577385 TI - Marrow transplantation in the treatment of patients with lymphoma. PMID- 2577386 TI - Effect of roxatidine acetate for handicapped patients under general anesthesia. PMID- 2577387 TI - The use of graphitized carbon black in solid phase extraction: comparison with C18 bonded silica gel. AB - Preliminary studies on the properties of a commercially available graphitized carbon black for the solid-phase (or liquid-solid) extraction of drugs and metabolites from biological fluids such as urine and plasma are described. A variety of basic drugs, all of the beta-blocker type, were efficiently extracted from dog plasma and subsequently recovered from the adsorbent using chloroform methanol mixtures. Similarly metabolites of the non-steroidal anti-flammatory drug ibuprofen also were efficiently extracted from human urine. The proportions of methanol and chloroform used for elution were found to be critical to ensure complete recoveries of adsorbed material. Proton NMR studies of the column eluates from both carbon and C18 bonded silica gel extraction cartridges revealed differences in capacity and selectivity following the application of ibuprofen containing metabolite samples. PMID- 2577388 TI - Advances in peritoneal dialysis/1989. Selected papers from the Ninth Annual Conference on Peritoneal Dialysis. Dallas, Texas, February 1989. PMID- 2577389 TI - Ca++ and 1,25(OH)2D3 enhance peritoneal macrophage (PMPhi) antimicrobial functions in CAPD. AB - Ca++ has been proposed as an intracellular second messenger for the activation of immune cells. An immune regulatory role for 1,25(OH)2D3 has also been suggested. We therefore evaluated the role of Ca++ and 1,25(OH)2D3 in the depressed antibacterial functions of 8 CAPD patients with relapsing bacterial peritonitis by evaluating in vitro the effects of escalating concentrations of 1,25(OH)2D3 and/or Ca++ on: 1. peritoneal macrophage (PMO) cytoplasmic Ca++; 2. PMO superoxide generation; 3. PMO leukotriene B4 release, 4. PMO bacterial killing. Results showed a dose-dependent increase in all parameters for Ca++ concentrations from 500 to 3,000 microM while with both a CA(++)-free medium and with Ca++ concentrations of 5,000 microM of medium all the aforementioned functions were abrogated. Addition of low doses of 1,25(OH)2D3 strongly potentiated the stimulatory effect of Ca++ on cell functions, while high doses were inhibitory. These in vitro data underline the importance of Ca++ and 1,25(OH)2D3 in PMO antibacterial functions in CAPD patients, and may be useful in the prophylaxis and therapy of peritonitis. PMID- 2577391 TI - Measurement of peritoneal lymph flow in CAPD using different osmotic agents. AB - No differences in lymphatic absorption ratio were observed using different osmotic agents (Glucose, Amino acid, glycorol). The differences in UF rate and intraperitoneal volumes during dialysis with these osmotic agents are soley dependent on the interactions between the osmotic agents (nature, strength) and the peritoneal membrane. PMID- 2577390 TI - Effects of Ca++ and 1,25(OH)2D3 on peritoneal immune-cell cytokine release and fibroblast proliferation in CAPD patients. AB - We have demonstrated the role in some CAPD patients with ultrafiltration (UF) loss of an increased peritoneal lymphocyte (PLy) and macrophage (PMO) Ca++ concentration in the release of large amounts of gamma-Interferon (gamma-IFN) and Interleukin-1 (IL-1), which stimulate peritoneal fibroblast proliferation. We have also shown in vitro and in vivo that the calcium channel blocker verapamil (VPM) is able to normalize the previously high Ca++ PLy and PMO concentration and cytokine release, to decrease fibroblast proliferation, and to increase UF in only 60% of the CAPD patients with UF loss due to a cytokine-mediated hyperproliferation of peritoneal fibroblasts, while in the remaining 40% there is little improvement in UF (VPM responders and low-responders, respectively). To evaluate which mechanisms in addition to passive Ca++ influx can play a role in the Ca(++)-dependent activation of peritoneal immune-cells, we evaluated in 6 CAPD VPM low-responder patients the effects of in vitro of different doses of Ca++ and 1,25(OH)2D3 on: 1) PLy and PMO cytoplasmic Ca++ levels in the PLy and PMO cytoplasm; 2) gamma-IFN and IL-1 release by PLy and PMO; 3) peritoneal fibroblast proliferation. Results showed a direct correlation between Ca++ levels in the medium and the PLy and PMO Ca++ concentrations, IL-1 and gamma-IFN release, and peritoneal fibroblast proliferation. These effects were enhanced by the addition of low doses of 1,25(OH)2D3 to the medium, while both high 1,25(OH)2D3 doses and verapamil abrogated the Ca+(+)-induced PLy and PMO activation. These results underline the importance of both Ca++ and 1,25(OH)2D3 in peritoneal immune-cell activation and peritoneal fibroblast proliferation, and may offer a new prophylactic approach for preventing UF loss in CAPD. PMID- 2577392 TI - First exchange neutrophilia is not always an index of peritonitis during CAPD. AB - To date, the medical literature suggests that CAPD patients with peritonitis have an increase in the dialysate white cell count (greater than 100 cells mL) with neutrophilia (greater than 50%). In order to explore the differential composition of the peritoneal fluid cells (P.F.C.), we have followed 21 patients (PTS) twice a month over a 30-month period. Nine hundred and fifty samples obtained either from the 24 hours (hrs) drained CAPD fluid, or from the "First Morning Exchange" (F.M.E.) during the same day, when possible, were estimated with the "Millipore Filter" (5-8 Micron (lw) pore size), stained by the Papanicolau method. The results can be so summarized: (1) 13 PTS (62%) showed constantly a low polynuclear count (3-32%); (2) 8 non-infected PTS (38%) showed constantly a higher neutrophilia (40-80%); and (3) from time to time the PTS of the two groups showed a higher neutrophilia and an increased cellularity during clinical infection. In all the samples, the differential P.F.C. count was not affected by the dialysate composition and no difference was observed between the 24 hrs samples and the F.M.E. samples made on the same day. Differential peritoneal cell count may be useful when there are important changes in the stable individual composition. PMID- 2577394 TI - Vancomycin therapy for gram-positive peritonitis in patients on CAPD. AB - We describe the use of vancomycin in the therapy of gram-positive peritonitis in patients on CAPD. Two ways of administration were in comparison: a) the intraperitoneal (IP) route, with the intraperitoneal administration of 30 mg/l vancomycin for 10 days and b) the intravenous (IV) route with 2 infusions of 1 gram of vancomycin, the first one on the day of the diagnosis of gram-positive peritonitis and the second 7 days later. Each one of these therapeutic schedules was applied at random for 20 episodes of peritonitis out of 40 episodes with gram positive organisms (28 Staph. albus, 10 Staph aureus and 2 Streptococcus). Remission of clinical symptoms occurred in 49-72 hours in both groups, while macroscopic clearing of dialysate effluent and sterilization of cultures were observed in 4-7 days. Recurrence of peritonitis was seen in 4 patients of the IV group 2 weeks after the administration of the second dose of vancomycin. We conclude that the use of vancomycin with either of the two ways of administration is of great value in the treatment of gram-positive peritonitis. The IV infusion was less successful but it seems to be useful for the out-patient treatment of gram-positive peritonitis. PMID- 2577393 TI - Are intracellularly penetrating antibiotics warranted in CAPD-related peritonitis? AB - Survival and growth of bacteria within peritoneal macrophages has been implicated as causes of recurrences and relapses of Staphylococcus epidermidis peritonitis. We compared the effect of cephradine--known not to penetrate into peritoneal macrophages--with that of clindamycin--known to concentrate in phagocytes--on the intracellular killing of S. epidermidis by human peritoneal macrophages. Clindamycine (q.i.d. 300 mg) or cephradine (q.i.d. 250 mg) was taken orally for one day in a randomized cross-over setting by 8 stable CAPD patients. On both days peritoneal macrophages were isolated from the overnight effluents and their capacity to phagocytize and kill S. epidermidis was measured. Phagocytes isolated from and incubated in effluents containing clindamycin, showed better bacterial uptake (32 vs 17%, p less than 0.01) and killing (70 vs 42%, p less than 0.01) compared to cephradine. Moreover, clindamycin prevented S. epidermidis to multiply intracellularly (-0.33 decrease in log colony forming units (cfu)/ml after 18 h). In sharp contrast, phagocytes incubated with cephradine allowed S. epidermidis to increase over 18 h (+1.48 increase in log cfu/ml; p less than 0.01 compared to clindamycin). We conclude that antibiotics with the ability to suppress intracellular bacterial growth may provide a more optimal treatment of CAPD-related peritonitis. PMID- 2577396 TI - Antibiotic activity against Staphylococcus epidermidis biofilms in dialysis fluids. AB - Infection associated with medical devices may be resistant to conventional antibiotic therapy. A potential mechanism explaining this variable therapeutic response is the presence of bacterial biofilms on the surface of the prosthetic material which may confer a biologically important protective function to the entrapped bacteria. To study these questions, we prepared standardized biofilms and conventional fluid phase cultures from a panel of ten Staphylococcus epidermidis strains. All ten strains showed in the fluid phase a variable pattern of sensitivity to seven antibiotics but were uniformly sensitive to rifampin and vancomycin. In the biofilm phase they demonstrated solid antibiotic resistance with the variable exception of rifampin. The nature of the milieu was a major variable. Fresh peritoneal dialysis solution enhanced the activity of rifampin but this effect was not present with spent or neutral dialysis fluids. PMID- 2577395 TI - Intraperitoneal Vancoled does not cause chemical peritonitis. AB - A prior report has suggested that loading doses of intraperitoneal Vancoled (vancomycin, Lederle) cause chemical peritonitis in patients with catheter infections. The present open-label study was conducted to determine the effects of a 30 mg/kg intraperitoneal loading dose of Vancoled given to five patients with a culture-positive, erythematous, draining exit-site infection. Prior to dosing, all dialysate was drained and sent for baseline cell count and culture. The loading dose was added to the dialysate and infused in the usual fashion. A sample of dialysate was drained at two hours and sent for cell count and culture. The entire exchange was drained at four hours and also sent for cell count and culture. Serum vancomycin concentrations wer measured at four hours. Baseline dialysate contained less than 9 white blood cells per microliter in all patients. Two and four hour samples contained less than 4 and less than 11 white blood cells per microliter, respectively. All fluid was sterile. WB C differential counts were unremarkable. No adverse effects occurred. The mean serum vancomycin concentration was 26.5 micrograms/ml. Intraperitoneal Vancoled did not cause chemical peritonitis and was well-tolerated by patients with exit-site infections. PMID- 2577397 TI - The effects of heparin on rifampin activity against Staphylococcus epidermidis biofilms. AB - Rifampin shows unique antimicrobial activity against Staphylococcus epidermidis biofilms, although in the in vitro situation rifampin resistance emerges rapidly by the selection of preexisting resistant mutants present in a small number in any large bacterial population. Fresh peritoneal dialysis solution is synergistic with rifampin suppressing rifampin resisters. The antimicrobial properties of rifampin are affected by heparin and protamine in entirely different directions. Heparin blocks the action of rifampin whereas protamine is synergistic producing a total bactericidal outcome. Protamine, when combined with heparin, unexpectedly did not influence the ability of heparin to antagonize rifampin. The mechanisms involved are unknown. The results are discussed in terms of known characteristics of the drugs and of the biofilm surface. PMID- 2577398 TI - Effect of monophosphoryl lipid A (MPLA) on peritoneal leukocyte function. AB - We analyzed the in vitro effects of monophosphoryl lipid A (MPLA), a nontoxic bacterial endotoxin-derived immunomodulant, on the depressed immune functions of peritoneal lymphocytes (PLy) and macrophages (PMO) of 6 CAPD patients with relapsing bacterial peritonitis. MPLA was also tested for its capacity to stimulate the peritoneal fibroblast proliferation as determined by 3H-thymidine incorporation. In vitro incubation of PLy and PMO with escalating doses of MPLA up to 5 micrograms/ml, resulted in a dose-dependent enhancement of Gamma Interferon (Gamma-IFN) and Interleukin-2 (IL-2) production by PLy, and Interleukin-1 (IL-1) by PMO. There was also an increase in PMO bacterial killing and membrane Fc receptor number, while no change in peritoneal fibroblast proliferation was seen with any of the MPLA concentrations tested. These results suggest that the peritoneal leukocyte abnormalities observed in some high peritonitis rate CAPD patients may be reversed, to some degree, by MPLA, without directly inducing a potentially deleterious peritoneal fibrosis. PMID- 2577399 TI - The effect of dwell time on peritoneal phagocytic defense of chronic peritoneal dialysis patients. AB - We studied the phagocytic capacity of peritoneal macrophages (PM) isolated from effluents after 4 different dwell times (1.5 to 15 hours) in six stable CAPD patients. In addition IgG and C3 levels as well as opsonic activity of the effluents were measured. Both IgG levels and opsonic activity increased significantly with prolonged dwell times. The same held true for the number of phagocytes and their phagocytic capacity. Thus prolonged dwell time enhanced both opsonic activity and phagocytic capacity significantly. As in CCPD the dwell time period between (dis)connection procedures is much longer than in CAPD, this might play an important role in the lower peritonitis rate among CCPD-treated patients. PMID- 2577400 TI - Serum and effluent lysozyme (muramidase) activity in CAPD patients. AB - The elevated serum lysozyme activity in 13 chronic renal failure patients (n = 26) dropped significantly during their first three months of CAPD and subsequently returned to initial levels. When compared with peritoneal mass transfer of lysozyme and serum creatinine levels, a distinct correlation was observed between these and the fluctuations in serum lysozyme activity recorded up to three years of CAPD (r = 0.319, P less than 0.05 and r = 0.425, P less than 0.025, respectively). A notable drop in the mass transfer of this low molecular weight protein took place after the first hour of dialysis. We concluded that long-term CAPD does not affect serum lysozyme activity and that passive loss across the peritoneal membrane could account for the lysozyme found in the effluent fluid. PMID- 2577401 TI - Quantitative method of measuring anti-viral activity of peritoneal dialysis effluent. AB - We have previously documented the presence of anti-viral activity in the peritoneal effluent of uremic patients treated by peritoneal dialysis. Anti-viral activity was determined by recording the inhibition of the cytopathic effect (CPE) of various viruses on Vero cells in a semi-quantitative manner based on observer's subjective judgment of the degree of inhibition of CPE. This degree of inhibition is a measure of the anti-viral activity. Although peritoneal dialysis effluent (PDE) was consistently seen to inhibit CPE we sought a quantitative method to accurately assess such anti-viral activity. To this end, the CPE of Parainfluenza virus (Para-3) on human kidney (Hu-K) cells was evaluated. The CPE of this virus is manifested by distinct plaques which can be easily counted after staining the tissue culture plate. Eighty-three (83) samples of PDE (0.5 ml) were added to Hu-K cells after which Para-3 was added. As control para-3 on Hu-K was used. The number of plaques obtained by virus control was taken as 100% CPE. The anti-viral activity of PDE was then recorded as the percentage of the CPE shown by virus control and averaged 20.9 +/- 28.6% (p less than 0.001 vs virus control). In addition PDE was diluted down to 1/64 concentration and the inhibitory effect again determined. Percent CPE of undiluted, 1/2, 1/64 PDE samples were 18.11 +/- 24.2, 33.57 +/- 18.16 and 77.93 +/- 17.4% respectively (p less than 0.01 between undiluted and 1/64 PDE). These data reaffirm that PDE possesses an inherent anti-viral activity which can now be quantitatively assessed using Para-3 on Hu-K cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2577402 TI - Atrial natriuretic peptide (ANP) is removed by peritoneal dialysis in humans. AB - Atrial natriuretic peptide (ANP) is a hormone liberated from the heart during atrial stretch (volume overload). In order to determine if ANP levels are altered in patients on continuous ambulatory peritoneal dialysis (CAPD) or affected by the dialysis procedure itself, we measured plasma ANP in patients before and after peritoneal infusion of two liters of 1.5% Dianeal dialysate and in dialysate subsequently drained from these patients. Plasma ANP is elevated in CAPD patients, but is not affected by infusion of dialysate. ANP is cleared from plasma by peritoneal dialysis. PMID- 2577404 TI - Hypophosphatemic effect of 1% amino acid dialysis solution. AB - Orally administered essential amino acids and their nitrogen free analogues have been shown to ameliorate hyperphosphatemia in uremic patients. The aim of the study was to assess the effect on serum phosphate and ionized calcium of a mixture of non-essential and essential amino acids, administered intra peritoneally as a 1% solution to a group of uremic patients who had been on continuous ambulatory peritoneal dialysis (CAPD) for at least three months. Serum phosphate and ionized calcium were measured at fortnightly intervals during the study period which lasted 16 weeks. All patients performed four 2 liter exchanges with dextrose dialysis solution for the first 4 weeks. Two of the four exchanges were then replaced by a 1% amino acid (AA) dialysis solution for a period of 8 weeks after which all patients reverted to their original regimen. Serum phosphate and calcium were measured fortnightly for a further 4 weeks. Serum phosphate fell significantly after introduction of the AA dialysis solution despite unchanged dietary protein and phosphate intake and no increase in the dose of oral phosphate binders taken by 2 of the 7 patients. Serum ionized calcium remained unchanged during the study period. PMID- 2577403 TI - Insulin influence (used as an additive to dialysate) on the mitogenic-induced effect of the peritoneal effluent in CAPD patients. AB - Peritoneal effluent in CAPD patients is the result of the interaction between dialysate and patient through the peritoneal membrane. Among the factors transferred from the patient to dialysate are solutes capable of stimulating fibroblasts: Interleukin-I, Interferon-gamma, and other proteins. Insulin is a well known mitogenic coadjuvant able to act sinergistically with other mitogens in the stimulation of fibroblast proliferation under experimental conditions. Our objective has been to study the effect of insulin added to dialysate in vivo on the in vitro mitogen-induced capacity of the nocturnal peritoneal effluent in 8 diabetics. Two different samples were studied: basal and with in vivo added insulin with the patients' usual doses. A Swiss 3T3 line of mice fibroblasts was used for studies, adding 50 microliters of peritoneal effluent. To confirm in vivo potential mitogenic activity, we also added PDBu (Phorbol dibuturate), a well known mitogenic agent, to both samples. Furthermore, another growth factor, EGF (Epidermal growth factor), was also added to 5 other samples. Insulin addition to the CAPD bag transforms a non-mitogenic peritoneal effluent into a mitogenic one (mean: 4.4 times over basal). At the doses used in vivo there is no linear correlation between insulin dose and DNA synthesis (r: -0.28, NS). Both PDBu and EGF in vitro addition induced a remarkable increment in the mitogenic capacity of the peritoneal effluent. We conclude that insulin added to CAPD bags behaves as a remarkable mitogenic coadjuvant for mice fibroblasts. Consequently, its long-term and universal clinical use should be reconsidered. PMID- 2577405 TI - Bone histology in CAPD patients: a comparison with hemodialysis and conservatively treated chronic uremics. AB - Thirteen patients treated with CAPD, 22 patients maintained on hemodialysis (HD) using aluminium-free water and matched for duration of treatment and 15 conservatively treated uremic patients (CONS) were evaluated by iliac bone biopsy to analyse the influence of CAPD on bone histomorphometry. CAPD patients were significantly (p less than 0.05) older (63.1 +/- 14.0, HD 52.7 +/- 13.3, CONS 53.3 +/- 11.7). Compared to HD the results were as follows: CAPD patients required significantly less aluminium to control hyperphosphatemia (0.16 vs. 0.49 g, p less than 0.005). They had a significantly lower incidence of symptomatic bone disease (p less than 0.05). Histomorphometry showed significantly lower osteoid volume (4.3 + 2.8% vs. 8.6 + 5.5%, p less than 0.05) and aluminium labelling intensity (0.15 vs. 1.0, p less than 0.05). Apart from bone mass indices, other histomorphometric variables showed an insignificantly more favourable trend in CAPD patients compared to HD. CONS patients had a significantly lower bone formation rate than CAPD (p less than 0.05), but otherwise no histomorphometric differences were observed. We conclude that CAPD patients require less aluminium therapy, have a lower risk of aluminium bone contamination, and may have a lower risk of developing uremic osteodystrophy. PMID- 2577406 TI - The effectiveness of protein supplementation on the nutritional management of patients on CAPD. AB - Repeated episodes of peritonitis cause malnutrition in CAPD patients because of increased protein loss into the dialysate, a high protein catabolic rate (PCR), and/or a decrease in appetite. The purpose of this study was to investigate whether protein supplements could improve the nutritional status of CAPD patients and secondarily reduce their incidence of peritonitis. Eight patients on CAPD were studied for 2 months as a baseline, then given protein supplementation for 4 months. There was significant (p less than .05) increase in dietary intake and nitrogen balance, with supplementation. The PCR decreased significantly (p less than .05). There was a concomitant decrease in the incidence of new episodes of peritonitis. In conclusion, protein supplementation can improve the catabolic state of CAPD patients. PMID- 2577407 TI - Comparative study of two different routes for insulin administration in CAPD diabetic patients. A multicenter study. AB - CAPD has been considered an appropriate method for treatment of diabetics in renal failure. Up to now the choice of route for insulin administration in these patients has not been definitely defined, although there is a general consensus for employing the intraperitoneal route for this purpose. However, contradictory data have appeared on this subject. Our aim has been to investigate whether the subcutaneous or intraperitoneal route makes any difference to metabolic control, and if so what is the price in terms of the incidence of peritonitis. Two groups of diabetic patients from three different hospitals with a similar peritonitis incidence and training protocols were studied. Of the 30 patients, 15 were treated with subcutaneous insulin (sc group) and in the other 15 the intraperitoneal route was employed (ip. group). The average follow-up period was 20.8 +/- 7.5 months for sc group and 18.7 +/- 8 months for ip. group. Insulin requirements were 30 +/- 11 u./day in the sc. and 110 +/- 60 u/day in the i.p. group (p less than 0.05) and remained constant during the study period. Metabolic controls (home glucose levels, HbA1C, hospital fasting glucose levels) were similar for both groups. However, the incidence of peritonitis was 4 times greater in the ip. group. In the ip. group 18 peritonitis episodes were registered in 280 patient-months vs 5 episodes in sc. group in 312 patient months. We conclude that the intraperitoneal route for insulin administration in diabetic CAPD patients produces a higher risk of suffering peritonitis with no real metabolic improvement in the medium term. PMID- 2577409 TI - Acid base correction in bicarbonate CAPD patients. AB - Bicarbonate has been proposed as buffer in CAPD solutions in recent years instead of lactate and acetate. The present study is designed to evaluate peritoneal bicarbonate kinetics using bicarbonate solutions. Seventy kinetic studies have been performed in 7 patients treated with 2 CAPD solutions containing 35 mmol/l (A) and 27 mmol/l (B) of bicarbonate. The changes in dialysate bicarbonate concentration at different dwell times were correlated with bicarbonate blood levels. Furthermore after 2 hours of dwell time and at subsequent observations, no differences in dialysate bicarbonate concentration were found between A and B solutions at the same bicarbonatemia. Thus a feedback between bicarbonate absorption and bicarbonate blood concentration was observed. If the amount of bicarbonate transferred to the patient is over the metabolic acid production, bicarbonatemia will rise: consequently bicarbonate dialysate absorption will decrease. After a few days, an equilibrium point will be reached. In this condition the bicarbonate absorption is equal to metabolic acid production and, in stable clinical conditions, a stable acid base status will be maintained by the patient. Our studies empirically demonstrated that the equilibrium is reached when a difference of 5 mmols between blood and inlet dialysate bicarbonate concentration is observed. Consequently to achieve 25 mmol/l of bicarbonatemia, the bicarbonate concentration of CAPD solution should be about 30 mmol/l. PMID- 2577408 TI - Variability of peritoneal clearances for apolipoprotein and its relationship to susceptibility for atherosclerotic changes in CAPD. AB - Apolipoprotein Clearance and Atherogenicity in CAPD: Protein and lipoprotein loss is one of the disadvantages of CAPD. The impact of these losses on serum constituents is not fully understood. Lipoprotein disorders are observed in patients with chronic or acute renal failure or undergoing dialytic therapy with resultant increase in atherosclerotic clinical events yet these phenomenon are poorly understood, underinvestigated and underreported. Thus the impact of dietary and pharmacological steps to prevent these events are limited by lack of clinical facts. The recent emergence of effective lipid lowering agents makes a rapid analysis of parameters important. We studied the relationships between peritoneal clearance of apolipoproteins and serum atherogenicity indicators in a preliminary study of 10 CAPD patients with and without peritonitis. We measured total cholesterol (TC), HDL-Cholesterol (HDL-C), Apo A-I and Apo B and dialysate levels of Apo A-I and Apo B. Apo levels were determined immunotubidimetrically, and dialysate was concentrated by ultrafiltration. A subsequent prospective group of 10 additional patients was studied to test the relationship found in the preliminary study. In both preliminary and prospective nonperitonitis groups, the ratio of peritoneal clearance of Apo A-I to Apo B correlated strongly with the serum TC/HDL-C (r = 0.9 preliminary, r = 0.78 prospective group). There was an inverse correlation between the clearance ratio and both serum HDL-C (r = -0.71 preliminary, r = -0.77 prospective group) and serum Apo A-I/Apo B (r = -0.74 preliminary, r = -0.62 prospective group).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2577410 TI - Serum B2 microglobulin (B2M) in CAPD. AB - Twenty-six chronic uremic pts (8F and 18M, mean age 64 yrs) on CAPD for 15 months on the average, were studied as regards the levels of B2M measured by radioimmunoassay in fasting serum samples. Considering residual renal function, 2 pts groups were identified: 11 pts with a diuresis greater than or equal to 500 cc/day and 15 pts with a diuresis less than 500 cc/day. Serum B2M was significantly decreased in the first group (24.8 +/- 8.1 vs 34.7 +/- 7.1 mg/l; p less than 0.02). Considering the incidence of peritonitis episodes, 12 pts without and 14 pts with one or more peritonitis episodes were noted. The group with no peritonitis showed significantly decreased serum B2M values (25.1 +/- 7.6 vs 35.03 +/- 4.8 mg/l; p less than 0.005). No relationship was found as regards primary renal diseases, sex and age of pts. We conclude that residual renal function and peritonitis episodes modify serum B2M levels in CAPD. The long term follow up of pts could be of interest for better defining the role of these factors as regards the incidence of pathologic lesions associated with B2M deposition. PMID- 2577411 TI - Plasma levels of atrial natriuretic peptide and digoxin-like immunoreactive substances in intermittent peritoneal dialysis. AB - Plasma atrial natriuretic peptide (ANP) and digoxin-like immunoreactive substances (DLIS) levels were assayed in 10 patients on intermittent peritoneal dialysis (IPD) before and after a 12 hour dialysis session. Ultrafiltration volumes and blood pressures, pre and post dialysis were recorded. Left atrial diameter (LAD), as determined by M-mode echocardiography was measured prior to and at the end of each dialysis session. Ten age matched patients on hemodialysis (HD) served as controls. Predialysis plasma ANP was significantly higher in HD as compared to IPD patients and dialysis resulted in a significant decrease of plasma ANP in IPD and HD patients (37.9 +/- 28.0 to 23.1 +/- 28.5 and 201.9 +/- 110.7 to 117.0 +/- 75.6 pg/ml, respectively, p less than 0.05). Ultrafiltration volumes in IPD averaged 1840 +/- 645 ml/dialysis. The corresponding decrease in body weight in HD was 2000 +/- 220 g. Total DLIS levels in IPD and HD did not change with dialysis. LAD decrease significantly post dialysis (41.3 +/- 5.0 to 38.6 +/- 5.7 cm, p less than 0.001). Calculated ANP clearance during IPD was 5.6 +/- 3.9 ml/min. Plasma ANP correlated significantly with ultrafiltration volumes and LAD. It thus appears that ANP is sensitive to volume status in dialysed patients. Its dialysance, in IPD, approaches that of other middle molecules. Under the conditions tested ANP does not influence DLIS levels. PMID- 2577412 TI - Peritoneal equilibration curve for beta-2-microglobulin (B2M) in CAPD patients. AB - To evaluate B2M removal during CAPD, the equilibration curve was determined in 9 CAPD patients (aged 67.9 +/- 6.5 years, treated for 19.0 +/- 17.4 months). The study was carried out on 2 consecutive days using 1.36% (day 1) and 3.86% (day 2) dextrose dialysis solutions for 6 hours each day. The B2M plasma value was the mean of 4 samples taken at the start and after 2, 4 and 6 hours. Dialysate values were determined on 3 ml samples taken every 30 minutes. The curve was fitted for dialysate to plasma B2M ratio (D/P) versus time to define the B2M equilibration curve. Our results showed that the value had a linear regression with both types of solution in all patients. The D/P B2M ratio was linear during the 6 hours of dwell time. Furthermore, there was no significant difference between the 2 solutions used. In conclusion, standard CAPD allows a low but constant B2M removal. An increase or a reduction in dwell time do not seem to have any influence on the B2M removal, which could be improved by methods other than varying dwell time and/or solution osmolarity. PMID- 2577413 TI - Automated peritoneal dialysis therapies--patient selection and dialysis prescription. AB - The various modalities of automated peritoneal dialysis are discussed with emphasis on advantages and disadvantages, relative efficiency in states of normal and abnormal peritoneal permeability, and patient selection. The importance of residual renal function, peritoneal solute transport, body mass, protein intake and catabolic rate in formulating peritoneal dialysis prescription is reviewed. PMID- 2577415 TI - Cycler dialysis evolution. AB - Use of automated cycler equipment is currently limited to a fraction of the peritoneal dialysis population. Various technical barriers combined in the past to inhibit its wider application. We have treated forty-seven patients over an eight year period with cycler dialysis, and have observed the evolution of this modality from a treatment of last resort to a first choice therapy for many patients--especially those who work. PMID- 2577414 TI - Continuous cyclic peritoneal dialysis--is it worth the extra effort? AB - Despite theoretical advantages of CCPD, only 1 of 13 patients trained in this modality continue on CCPD in a 3 year review period. Average duration on CCPD was only 7 months. When compared with our CAPD population higher transplant rates, death rates, and dissatisfaction with the dialysis technique, but not higher peritonitis rates were reasons for terminating CCPD. PMID- 2577416 TI - Freedom Set II--a Y-set CAPD system with a novel design. AB - The Freedom Set II is designed with a three-way valve to control the direction of dialysate flow thus simplifying the procedure and decreasing training time. Twenty-four patients from two centers were trained on the Freedom Set II and were observed for ninety patient months. Five patients who had been on other bagless systems expressed their preference for the Freedom Set II. The peritonitis rate for the observation period was one episode every 21 patient months. We conclude that the Freedom Set II provides safe, cost-effective dialysis and simplifies the CAPD procedure. PMID- 2577417 TI - Comparison of peritonitis rates with CCPD, manual CAPD, Y-sets, O-sets, UV devices and sterile weld. AB - The peritonitis rates observed with various peritoneal dialysis techniques and connectors are analyzed based on literature results and a large center experience. It is apparent that techniques sharing an initial dialysate flush following a connection are superior in reducing the rate of peritonitis. Connecting and sterilizing devices may help prevent peritonitis in high risk groups and often facilitate the connecting procedure by serving as patient assist devices. PMID- 2577418 TI - Comparison of two non-disconnect CAPD delivery systems. AB - Intraluminal transmission of bacteria remains a significant factor in the morbidity and procedural success of CAPD. A worsening rate of peritonitis in a longstanding CAPD program (first patients 1978) led to a search for a system which might allow a lesser rate of peritonitis. Simplicity in the procedure was a requirement. For this reason disconnect systems were not considered. The Travenol spike system was prospectively compared with Delmed leur lock in terms of rate of peritonitis and difficulty in training. The former had been used by the center since inception of the CAPD program. 28 patients new to CAPD were alternately assigned to each system without other bias, including diagnosis, age, sex, or race. The study, while ongoing, was analyzed at 12 months. 66 patient months were involved with each system. The peritonitis rates were: 2.2 episodes: patient year with the Travenol; 0.9 episode:patient year for the Delmed systems. The Delmed system appears to provide a lower rate of peritonitis. In addition, less manual dexterity, steadiness, and hand eye coordination are necessary. PMID- 2577419 TI - Soft tissue complications of Tenckhoff catheters. AB - Soft tissue complications (STC) involving the catheter tract and exit site continue to be a significant source of morbidity (40%) and cause for catheter removal (8%). Inner cuff infections, accompanied by peritonitis and managed with catheter removal, occurred in 6% of catheters. All other STC can be managed without catheter removal. STC presenting without peritonitis have not been associated with an increase in peritonitis related catheter loss. PMID- 2577420 TI - Induced changes of the peritoneal diffusion capacity by smoking, intraabdominal hypertension and omentectomy. AB - Peritoneal membrane suffers in some CAPD patients changes which modify its functionalism. In order to know whether these changes could be expected or appropriate, it is necessary to explore the general and particular conditions which can alter peritoneal physiology. Three aspects, smoking, intraabdominal hyperpressure and and omentectomy are situations which have not been included in the studies of peritoneal physiology. PATIENTS: The control group was constituted by 23 patients. Diabetics were studied as a separate group, with their own 10 patient controls. Smokers (1-20 cigarettes per day): 15 were non-diabetic patients, 9 were females. Diabetic smokers: 7 patients. Intraabdominal hyperpressure was determined by two big polycycstic kidneys (PCKD) in 8 patients, none diabetic. Omentectomy was performed in 6 non-diabetic and 9 diabetic patients. In all cases the procedure was prescribed because of an early catheter entrapment. Smoker patients show significant higher MTCs values for urea and creatinine than controls, but the slightly lower ultrafiltration value did not reached significant difference. Polycystic kidney patients showed lower MTCs values in respect to controls. Ultrafiltration capacity was similar. Omentectomized patients did not show any differences in respect to controls. In the diabetic patients group, neither ultrafiltration nor MTCs values presented significant differences between the established subgroups. So, smoking did not seem to induce higher MTC values as in the non-diabetic group. In conclusion, and according to the present results, two more situations should be taken into account in the evaluation of the peritoneal membrane dialyzing capacities: smoking, which increases diffusion capacity except for diabetics and PCKD with tow big kidneys, which decreases this capacity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2577422 TI - Low peritoneal clearances--differential diagnosis and management. AB - The magnitude of peritoneal solute clearance is analyzed in terms of: 1) population mean, 2) preservation during long-term therapy, 3) values obtained with hemodialysis, and 4) requirements to maintain patients free of uremic signs and symptoms. The peritoneal equilibration test (PET) has been used successfully to characterize peritoneal solute transport rates and to formulate more adequate dialysis prescription. Serial PET's can also provide a valuable prognostic index of peritoneal membrane function. The experience with mechanical and physical maneuvers to enhance peritoneal clearance is reviewed. PMID- 2577421 TI - Changes in peritoneal membrane transport rates in patients on long term CAPD. AB - Peritoneal equilibration tests (PET's) are a simple means of monitoring peritoneal membrane function in C.A.P.D. patients. Findings on initial testing have been proposed as having prognostic value for a patient's course on peritoneal dialysis. 177 serial P.E.T.'s were performed in 49 patients at six monthly intervals using a 2 litre 4.25% dextrose exchange and a four hour dwell and equilibration ratios were calculated for urea (D/P U), creatinine (D/P C) and glucose (D/Do G). Alterations in equilibration ratios with time were not significant in the group as a whole. However, a subgroup of 12 patients was identified in whom there were significant increases in D/P U (p .02) and in D/P C (p .003) and decreases in D/Do G (p .025) between zero and 18 months. A subgroup of five patients in whom D/P U decreased significantly (p .05) was also identified. These subgroups did not differ significantly in clinical characteristics although peritonitis was more frequent in the group with increasing transport. As results of P.E.T.'s alter with time in many patients prognostication based on initial values only may not be valid. PMID- 2577423 TI - Relationship between upper gastrointestinal symptoms and lesions on CAPD patients. AB - In order to establish a relationship between upper GI symptoms and CAPD therapy, 34 CAPD patients underwent UGI endoscopy and X-ray studies. Endoscopy is more specific than upper GI X-ray series in the diagnosis of gastrointestinal lesions. PMID- 2577424 TI - Cardiac output with CO2 rebreathing method in CAPD patients. AB - The aim of this study is to evaluate cardiac output (CO) with CO2 rebreathing method (RCO2) in patients (pts) on CAPD. We have studied 15 pts on CAPD from at least 6 months, the mean (+/- SD) age was 55 +/- 4 years, mean (+/- SD) hemoglobin was 10 +/- 2 gr/dl. The respiratory tests excluded obstructive or restrictive broncopneumopathies. Electrocardiograms and B-mode echocardiograms were normal. RCO2 was evaluated using the FICK formula: CO = VCO2/CvCO2 - CaCO2 where VCO2 is CO2 production; CvCO2 is the CO2 content in venous mixed blood; CACO2 is arterial CO2. VCO2 was obtained by collecting expired air into a Douglas bag during respiration at rest for 4 minutes. CvCO2 was obtained after 10-15 seconds of respiration in a mixture of 7% CO2 in O2. CaCO2 was obtained at CO2 end-tidal capnogram. RCO2 was performed in CAPD with full and empty abdomen. The mean (+/- SD) CO was 2.3 +/- 1.04 l/min with both full and empty abdomen, values below those theoretically calculated, taking into account the age and body surface (4.7 +/- 0.6 l/min P less than 0.0005). The reduction of CO is not induced by left ventricular insufficiency, but such phenomenon could be attributed to a redistribution of body fluid between intra and extracellular, in favour of the intracellular compartment. Therefore the increase in hematocrit and total plasma proteins can be fictitious. PMID- 2577425 TI - The influence of dialysis solution on the exercise capacity in patients on CAPD. AB - The present study was conducted to see whether the exercise capacity can be altered by intraperitoneal dialysis solution in patients on CAPD. Symptom-limited progressive treadmill tests with respiratory gas analysis were performed in patients on long-term CAPD, and exercise time (ET), maximal oxygen uptake (VO2 max) and ventilatory anaeorbic threshold (AT) were obtained. The treadmill tests were carried out before and after the drainage of 2-liters of dialysis solution. The dialysate bag with the fluid had either been carried by patients on their backs (test A) or been kept apart from their bodies (test B) during exercise, i.e. an apparent body weight in test B without the CAPD bag decreased by 2 kg as compared with the control. VO2max, AT or ET in test A did not change, whereas ET in the test B was prolonged after the drainage of dialysis solution (before: 437 +/- 170 sec, after: 479 +/- 158 sec, n = 10, p less than .01). No change was noted in VO2max or AT in test B. We conclude that the dialysis solution retained in the peritoneal cavity affects ET by acting as an extra-weight, although the solution has no influence on VO2max and AT. PMID- 2577426 TI - Dialysis for the elderly: survival and risk factors. AB - We evaluated survival and risk factors in 86 elderly patients (pts) who underwent dialysis at one center throughout the last 10 years. Thirty-five pts received hemodialysis (HD), 32 intermittent peritoneal dialysis (IPD), and 19 continuous peritoneal dialysis (CAPD). Risk factors included: treatment, age, sex, underlying disease, heart failure (HF), peripheral vascular disease (PVD), diabetes mellitus (DM) and malignancy. Median age was 65 years for both HD and CAPD, and 69 for IPD (p less than 0.05). Survival evaluation demonstrated a longer life span for HD vs. IPD (p = 0.02) for CAPD vs. IPD (p = 0.03) and no difference between HD and CAPD pts. Cox analysis showed higher death odds ratio (OR = 2.4) for IPD vs. HD and lower ratio for CAPD vs. IPD (OR = 0.3). Other OR positive risk factors were: HF, PVD, DM and malignancy. The median value of risk factors for each group was higher for both IPD and CAPD vs. HD. Both life span and death OR for CAPD were equal to HD in spite of higher risk factors in CAPD group. The lower survival of the IPD group may be due to its older age. CAPD should represent the elective treatment for elderly uremics while HD or IPD should be reserved for selected patients. PMID- 2577427 TI - CAPD versus hemodialysis (HD): 7 years of experience. AB - The purpose of this work is to compare survival and drop-out in 2 groups of patients undergoing either CAPD (42 pts) or standard HD (48 pts) as first treatment, from November 1981 to December 1988. Mean age and number of risk factors were not significantly different. At the end of the study 50.0% of pts on CAPD and 37.5% on HD were still on first treatment; clinical problems were the most frequent cause of drop-out. The total period of observation was significantly higher in the CAPD group (1391.0 months vs 850.4), but the life table analysis showed no significant differences in the incidence of death and of drop-out in the two groups. The follow-up of the CAPD group was subdivided into two periods, due to the fact that a scheme for clinical and social survey of patients undergoing dialysis and a policy of more frequent home visits were introduced at the end of 1985. A significant decrease of peritonitis episodes was observed in the second period. PMID- 2577429 TI - Recovery of renal function in patients treated by CAPD. AB - Recovery of renal function was observed in 10 out of 300 patients (3.3%) treated by CAPD. These 10 patients presented the following primary renal diseases: 4 nephroangiosclerosis, 4 interstitial nephropathies, 1 diabetic nephropathy, 1 unknown nephropathy, and were treated by CAPD for a mean period of 10.2 +/- 5.5 months. CAPD was discontinued when residual renal function reached 12 ml/min. After recovery 8 patients were still alive, including 1 patient who returned to dialysis. 2 patients died. When risk factors such as uncontrolled hypertension, cardiac failure, severe nephrotic syndrome, rapidly progressive renal failure, analgesics or non steroidal anti-inflammatory drug treatments or abuses, chronic urinary obstruction, cholesterol emboli were associated with end stage renal failure, CAPD should be the dialysis treatment of choice, expecting the preservation of the kidney capacities and further a recovery of renal function. PMID- 2577428 TI - CAPD in a large population: a 7-year experience. AB - In this report we evaluate the results obtained with CAPD in uremic patients in Piedmont, a Northern Italian region (4.4 million inhabitants) during the last 7 years. Data are gathered from the computerized records of the regional dialysis and transplantation registry, which collects information on 3,567 pts, 2,243 of which entered since Jan. 1981 and 1,808 alive at Dec. 1987. Among these, 193 (11%) were on CAPD, a figure almost constant in the last 7 years. However CAPD diffusion is not uniform among the 20 centers of the region, ranging from 0 to 49.5% of the patients on dialysis. CAPD is particularly employed in the elderly (47.5% of the patients being older than 60 years and 19.5% over 70). This treatment was the first choice in 16% of the patients admitted to dialysis between 1981-87; this figure reaches 33% for the diabetics. High drop out rates still represent a major problem, in a 6 year follow up 66% of the patients being transferred to another dialysis treatment. Peritonitis is the main cause of drop out (22%), while loss of peritoneal membrane efficiency accounts for 7%, patient's choice 14%, catheter complications 14%, inability to cope 8%, clinical problems 20% and other reasons 15%. Drop out rate is not influenced by the presence of high risk condition or age. Survival curves show no significant difference for CAPD in comparison to hemodialysis in all the age groups considered. This epidemiological survey, based on a global 522 pts experience extended over a 7 year period, indicates that CAPD is a competitive mode of treatment in chronic uremia. PMID- 2577430 TI - Need of a partner on home peritoneal dialysis (HPD): incidence and an alternative choice. AB - Among 63 patients (pts) on HPD 26 (41.7%) had need of a partner (PN) in conducting dialysis. In most cases the role of a partner is performed by the consort (26.9%) or by a son or daughter (19.3%). Forty-four percent of all partners worked in the home. The PN is significantly higher (P = 0.0001) in pts aged 65 or more. The most frequent cause of PN (38.6%) was a memory and learning deficiency (MLD) of the exact sequence of dialysis maneuvers, in particular in elderly pts. The Talking Cricket (TC), a tape recorder device with a series of automated and safety features, conceived and settled in our center to guide the patient through the dialysis procedures at home, represents a valid alternative choice to the partner in pts with MLD. Seven pts with MLD, aged between 69 and 80 years, used the TC at home with a Y-set with Amuchina. During a follow-up of 84.4 months we observed 3 peritonitis episodes, 4 accidental infusions of disinfectant in to the peritoneal cavity; and 3 pts discontinued the use of the TC. The TC has been used in the hospital to train 5 pts undergoing CAPD: standardization and uniformity of teaching facilitates both learning by the patients and teaching by the nurses. PMID- 2577431 TI - A clinical study of 2.5 liter exchange volumes. AB - Comparisons of peritoneal clearances, hematologic and biochemical assays were performed on eleven CAPD patients using 2 liter and 2.5 liter daily exchanges. Group 1 consisted of 8 patients substituting all four daily 2 liter exchanges. These patients experienced statistically significant increases in urea and creatinine clearance (an average of 15% and 10% respectively). Corresponding reductions in serum levels occurred (8% and 9% respectively). Ultrafiltrate volume increased by an average of 12%. Group II consisted of 3 patients that substituted one 2 liter exchange. These patients also experienced increases in urea and creatinine clearance (8% and 11% respectively) and decreases in corresponding serum levels (1% and 4% respectively). Ultrafiltrate volume increased an average of 12%. After one month on the 2.5 liter regimen, patients were surveyed for their reactions to larger exchange volumes. Ninety-one percent of patients decided to continue using the 2.5 liter volume. Reasons cited included feeling better and having better weight and fluid control. None of the patients demonstrated complications such as catheter leakage or hernias. The use of four daily 2.5 liter exchanges can provide over 20% more clearance for many CAPD patients currently using 2 liter exchanges. This survey demonstrates most patients tolerate 2.5 liters, and they feel better. A 2.5 liter regimen may be indicated for patients who could benefit from more dialysis and for those at risk of dropping out of CAPD due to inadequate dialysis. PMID- 2577432 TI - A collection of problems in CAPD. AB - Several isolated problems, which in magnitude may appear small, yet can be enormous management problems, are discussed. In most instances experience is limited and literature is sparse. An attempt has been made to collate personal experience with that from the literature in arriving at guidelines for management of these problems. PMID- 2577433 TI - The effect of calcium antagonists on the peritoneal membrane in patients on CAPD. AB - In order to evaluate the effect of Calcium Antagonists on the permeability of the peritoneal membrane in patients on CAPD, the peritoneal clearances, the mass transfer, the ultrafiltration and the mass transfer area coefficient (MTAC) were measured. We studied 10 patients before and after the instillation of 10 mg (5 mg/L) of Verapamil into the peritoneal cavity. Our results showed a significant (p less than 0.05) increase of urea, creatinine and uric acid clearances. A significant increase (p less than 0.05) in the ultrafiltration and MTAC was also observed, while the mass transfer of electrolytes K+, Na+ and Ca++ was unchanged. These findings indicate that the intraperitoneal use of verapamil may induce an increase in the peritoneal permeability in patients on CAPD. PMID- 2577434 TI - A review of management of pleuroperitoneal communication in five CAPD patients. AB - Development of massive hydrothorax is well known in CAPD patients. Five CAPD patients at one center have developed some form of pleuroperitoneal communication as evidenced by pleural effusion. Temporary discontinuation of CAPD, tetracycline instillation, and surgical patch grafting of the diaphragm have been used as treatments for the communication. PMID- 2577435 TI - Indirect inguinal hernia in CAPD patients with polycystic kidney disease. AB - We have experienced a high incidence of indirect inguinal hernias occurring in the first few months of starting CAPD in male patients with autosomal dominant polycystic kidney disease (PKD). Out of 13 patients with P.C.K. on CAPD one (7.7%) had inguinal herniorraphy at an early age and six (46.2%) developed bilateral indirect inguinal hernia during CAPD. In comparison only one of 30 other male patients on CAPD developed indirect inguinal hernia and none had any evidence of previous inguinal herniorrhaphy or of indirect inguinal hernia on clinical examination. Five out of seventeen (29.4%) male patients with P.C.K. on hemodialysis or conservative treatment of renal impairment had history of inguinal herniorrhaphy or an evidence of inguinal hernia on clinical examination. This compares with a rate of herniorrhaphy performed for indirect inguinal hernia approximately 1.5 per 1000 population. In one patient on CAPD a peritoneogram using 99m Tc sulfur colloid suggested a patent processes vaginalis to account for scrotal edema on one side; the patient subsequently developed an indirect inguinal hernia on the other side just a few months after the repair. In view of high association of patent processus vaginalis with P.C.K. we recommend it is routinely searched in this group of patients and repaired at time of CAPD catheter insertion. PMID- 2577436 TI - Grey-Turner's sign in sclerosing peritonitis. AB - A 41-year-old CAPD patient developed Grey-Turner's sign during the course of bacterial peritonitis due to Pseudomonas aeruginosa. At the same time a diagnosis of sclerosing peritonitis was made by CT-scanning of the abdomen. We think that Grey-Turner's flank staining could either have been caused by synthesis of proteases by the Pseudomonas bacteria or by reduced mesenteric flexibility and increased vascularization of the peritoneum due to the sclerosing peritonitis. This could have led to spontaneous mesenteric bleeding with leakage to the retroperitoneal tissues. A possible relationship with an ascites puncture is less likely. PMID- 2577437 TI - Hypertension in dialysis patients: does CAPD provide an advantage? AB - We considered the hypothesis that CAPD is a superior treatment to HD in patients with dialysis-refractory hypertension. We compared 12 HD patients to 22 CAPD patients entered to our program over a one year period. All had been treated for hypertension before dialysis. We found that systolic blood pressure decreased in CAPD patients compared to HD patients, even though medications were more commonly reduced in CAPD patients compared to HD patients. Ten CAPD patients required no medications after one year's treatment. These preliminary data in this small pilot study support the notion that CAPD is superior to HD in blood pressure management of hypertensive patients. A large, multicenter study may be warranted to determine if CAPD favorably influences the risk of cardiovascular complications in dialysis patients compared to HD. PMID- 2577438 TI - A hemostasis study in CAPD patients during fibrinolytic intraperitoneal therapy with urokinase (UK). AB - Catheter obstruction due to fibrin deposits during CAPD can cause poor outflow of peritoneal fluid and recurrent peritonitis. In order to treat this complication, 75,000 IU of diluted Urokinase (UK) were infused into catheters obstructed by fibrin in 10 CAPD patients (4 of which had peritonitis), without adverse reactions. After 60 minutes, a 2 liter exchange of peritoneal fluid was performed. In all the cases a normal outflow was restored. Hemostasis parameters (PT, PTT, TT, Fibrinogen, FDP, Fibrin monomers, BT, AT III) and blood cells count (RBC, HGB, HCT, WBC, PTL), were assayed before and two hours after the UK infusion, and did not show any significant variation, except for a decrease of white blood cells, which remained, however, within the normal range. No peritonitis episode occurred in the follow-up period. UK fibrinolytic therapy is safe and effective in treating fibrin obstruction of CAPD catheters without catheter removal and prevents recurrent peritonitis. PMID- 2577439 TI - Neuronal calcium channels: kinetics, blockade and modulation. PMID- 2577440 TI - Ontogeny of amino acids related to excitatory amino acidergic transmission in the rat forebrain. AB - Developmental changes in the concentration of putative amino acid neurotransmitters were investigated in the forebrain of prenatal and postnatal rats. Glutamate and aspartate, which interact with three-typed agonist sites of excitatory amino acid receptors, decreased until birth and then increased with maturation. Agonists for strychnine-insensitive glycine sites, i.e., glycine, serine and alanine, showed progressive decreases in the postnatal period. Although alanine rapidly decreased in preterm, there was no change in glycine and serine contents in this period. These developmental patterns of the compounds related to EAA transmission differed from those of inhibitory amino acid transmitters. GABA showed a steady increase during ontogeny. Taurine increased until birth and then decreased to the adult level. These results suggested that the ontogenic profile for EAA is different from that for the glycine receptor agonists and that other inhibitory amino acid transmitters develop with patterns different from those of amino acids related to EAAergic transmission. PMID- 2577441 TI - [Chlordesmethyldiazepam and prolactinemia during surgical stress]. AB - The per-operative plasma prolactin levels in 16 male patients undergoing plastic reconstructive surgery were studied. 8 patients received chlordesmethyldiazepam 0.1 mg/kg-1 i.v. (group C), 8 sodium thiopental 5 mg/kg-1 i.v. (Group T) in anaesthesia induction. All patients were premedicated by diazepam 0.15 mg/kg-1 by mouth 90 min. before anaesthesia induction and atropine 0.007 mg/kg-1 i.v. just before induction, and received succinylcholine 1 mg/kg-1 i.v. and an endotracheal tube for mechanically controlled ventilation. Anaesthesia maintenance was assured by isoflurane 0.5-2.5% in a N2/O2 (2/1) gas mixture. Blood samples were collected from each patient at the following times; 24 h before surgery (t0); 30 min after skin incision (t1); 30 min after extubation (t2). Significant variation of blood prolactin levels are not been shown. PMID- 2577442 TI - A Markov process based model of the neurotransmitter-receptor binding process in the brain--comment. PMID- 2577443 TI - Antigen-specific immune regulation. PMID- 2577444 TI - Human gene mapping and linkage analysis. PMID- 2577445 TI - Human T-lymphotropic viruses. PMID- 2577446 TI - Drug analysis. The Third International Symposium. May 1989, Antwerp, Belgium. PMID- 2577447 TI - Oxidation of beta-blocking agents--VII. Periodate oxidation of labetalol. AB - The oxidation of labetalol with sodium metaperiodate is described. In spite of the bulky substituent on the amino group of labetalol, glycol cleavage of the molecule occurred. Spectrometric methods verified that the aromatic aldehyde formed was 2-hydroxy-5-formylbenzamide and that the amine was 1-methyl-3 phenylpropylamine. The polarographic behaviour of the aldehyde was examined as well. The half-wave potential in Britton-Robinson buffer pH 5.68 was -1.24 V. Direct linearity (r = 0.9999) was observed between the diffusion current and the concentration of the aldehyde. Quantitation of labetalol was carried out polarographically by measuring the concentration of 2-hydroxy-5-formylbenzamide formed in the oxidation. PMID- 2577448 TI - The determination of fenspiride in human plasma and urine by liquid chromatography with electrochemical or ultraviolet detection. AB - A selective and sensitive method for the determination of fenspiride in biological fluids is described. The method involves liquid-liquid extraction followed by separation on a reversed-phase column with electrochemical detection for low levels of the drug in plasma (less than or equal to 100 ng ml-1) or UV absorption for higher concentrations in plasma or urine. The method is suitable for pharmacokinetic analyses and drug monitoring studies. PMID- 2577449 TI - High-performance liquid chromatography of deacetylmetipranolol in plasma. AB - A sensitive high-performance liquid chromatographic method with electro-chemical detection is developed for the determination of deacetylmetipranolol (DMP), an active metabolite of beta-sympatholytic drug metipranolol (MP). DMP is extracted from the plasma after basifying with dichloromethane. After evaporation, the residue is reconstituted in the mobile phase, injected onto the reversed-phase ODS column and chromatographed at 50 degrees C. The sensitivity of the method is 2 ng of DMP in 1 ml plasma. Pindolol, another beta-blocking agent is used as internal standard. The method is used for a pharmacokinetic investigation of MP in healthy volunteers and in the patients with liver cirrhosis. PMID- 2577450 TI - [Type 1 fimbriae and P fimbriae in E. coli producing chronic prostatitis]. AB - The fimbriated adhesines constitute a factor of virulence of E. coli in the urinary tract infections. The presence of type 1 fimbriae and fimbriae P was evaluated in 23 E. coli strains isolated with patients with chronic bacterial prostatitis. For the diagnosis of prostatitis the Stamey test was used. The detection of the type 1 fimbriae was carried out by agglutination of the E. coli strains with Saccharomyces cerevisiae and that of fimbriae P with PPA test. 95.7% of the evaluated strains had type 1 fimbriae and 52.2% had fimbriae P. It is concluded that type 1 fimbriae are common in all strains associated with urinary tract infection, without any relationship between their presence and the localization of infection, and that the presence of fimbriae P is not a constant feature of the E. coli strains associated with chronic prostatitis. PMID- 2577451 TI - A strategy for the determination of beta blockers in plasma using solid-phase extraction in combination with high-performance liquid chromatography. AB - This paper describes a general approach for the therapeutic drug monitoring of 13 different beta blockers in plasma. The chromatographic system contains a cyanopropyl-bonded phase as a stationary phase in combination with a mobile phase composed of acetonitrile and phosphate buffer (pH = 3, mu = 0.05). Two modes of detection are used, namely, UV detection and fluorescence detection. The sample pretreatment is performed with a nitrile-sorbent in combination with methanol phosphate buffer (pH = 3, mu = 0.05) or with methanol containing 0.1% propylamine as eluent. Acceptable recoveries are obtained for practolol, acebutolol, pindolol, oxprenolol, mepindolol, atenolol, propranolol, prenalterol, alprenolol, metoprolol, sotalol and nadolol. For labetalol, however, the elution recovery has to be improved. Finally, this approach is illustrated by the assay of nadolol in the plasma of patients suffering from hypertension, who had received an oral formulation of the drug. PMID- 2577452 TI - The simultaneous determination of active ingredients in cough-cold mixtures by isocratic reversed-phase ion-pair high-performance liquid chromatography. AB - A simple, rapid and accurate method for the simultaneous determination of active ingredients in cough-cold mixtures using isocratic reversed-phase ion-pair high performance liquid chromatography has been developed. It involves the use of an octadecylsilane column as the stationary phase with methanol, water, tetrahydrofuran, phosphoric acid mixtures as mobile phase including sodium dioctylsulphosuccinate as the ion-pair agent. The pH of the mobile phase was adjusted to 4.6 by means of phosphoric acid and ammonium hydroxide solutions. The proposed method involves the simple dilution of the samples with the mobile phase and the addition of metoclopramide hydrochloride as the internal standard. The active ingredients under investigation were chlorpheniramine, codeine, diphenhydramine, ephedrine, ethylmorphine, phenylephrine, phenylpropanolamine and pholcodine, which exist as various combinations in cough-cold mixtures. The optimum composition of the mobile phase and the optimum flow rate were determined and are reported. The method was applied to the determination of active ingredients in seven commercially available cough-cold mixtures. PMID- 2577453 TI - Potentiometric and calorimetric assay of mephenoxalone. PMID- 2577454 TI - The National Heart, Lung and Blood Institute workshop on antihypertensive drug treatment: The benefits, costs, and choices. Bethesda, Maryland, June 11-12, 1987. PMID- 2577455 TI - Antihypertensive drug use. Trends in the United States from 1973 to 1985. AB - Hypertension, a major public health problem, often requires drug therapy. We examined trends in outpatient antihypertensive drug use in the United States from 1973 to 1985. The numbers of prescriptions and the diagnostic and drug treatment information were obtained from the National Prescription Audit (Ambler, Pa, IMS America, 1985) the National Disease and Therapeutic Index (Ambler, Pa, IMS America, 1985), ongoing surveys of pharmacies, and office-based physicians. We adjusted drug-use data for the fact that several antihypertensive drugs also have other uses. During the study period, the annual numbers of prescriptions for treatment of hypertension progressively increased from 128.1 to 208.6 million, an average change of 5% per year. In 1973, the three leading classes of antihypertensive drugs were thiazide diuretic agents, peripheral neuronal inhibitors, and central alpha-adrenergic receptor stimulators. By 1985, the thiazide drugs were still the leader, followed by beta-adrenergic receptor blockers and potassium-sparing diuretic drugs. The use trends presented are consistent with surveys indicating increased drug therapy of hypertension from 1960 to the present. PMID- 2577457 TI - alpha 1-antagonists in the treatment of hypertension. AB - A number of agents are now available to treat hypertension. One relatively new class of agents is the selective alpha 1-inhibitors, which have distinct advantages over earlier nonselective alpha-adrenergic receptor-blocking agents. Three alpha 1-inhibitors are reviewed in this article: prazosin, terazosin, and doxazosin. These alpha 1-inhibitors are similar in chemical structure and pharmacological action. alpha 1-Inhibitors lower blood pressure by reducing vascular tone in resistance and capacitance vessels. alpha 1-Inhibitors are similar in effectiveness in blood pressure lowering to other commonly used antihypertensive agents like the thiazide diuretic drugs and beta-blockers, which are efficacious as monotherapy in lowering pressure, as initial agents, or in combination with other antihypertensive agents in multidrug therapeutic regimens. alpha 1-Inhibitors are associated with a reasonably low incidence of serious adverse effects and are essentially free of any adverse metabolic effects. alpha 1-Inhibitors have been shown to beneficially effect blood lipids in several studies. The favorable lipid effect makes alpha 1-inhibitors especially appropriate to use in diabetic hypertensive and other patients with elevated serum lipid levels. The beneficial lipid effects may enhance the ability of alpha 1-inhibitors to prevent coronary heart disease, an outcome that has been difficult to demonstrate in thiazide-based trials. PMID- 2577458 TI - Cost-effectiveness of antihypertensive treatment. General considerations. AB - Cost-effectiveness analysis, a set of methods for estimating the costs and health effects of medical interventions, helps decision makers to compare alternative treatments and to decide which interventions are appropriate in which situations. This article outlines some fundamental principles of cost-effectiveness analysis and discusses the characteristics necessary if alternative therapies are to be more cost-effective than traditional drug treatment for hypertension. The discussion focuses primarily on the newer drugs like angiotensin converting enzyme inhibitors, alpha-adrenergic receptor blockers, and calcium antagonists. PMID- 2577456 TI - Traditional first-line therapy. Overview of medical benefits and side effects. AB - When diuretic-based stepped care was first advocated for the treatment of hypertension, there were fewer classes of antihypertensive medication than there are today. In 1984, the third Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC) for the first time suggested an alternative initial treatment with a beta-blocker in selected hypertensive patients, and the fourth JNC report has recommended the alternatives of calcium channel blockers or angiotensin converting enzyme inhibitors for step-one therapy as well. However, only the diuretic drugs and beta-blockers have been shown to reduce cardiovascular morbidity and mortality in prospective, long-term, controlled trials. Moreover, 30 years' experience with diuretic agents and 20 years' experience with beta-blockers have defined the advantages, disadvantages, and potential side effects of these drugs more precisely than is possible for newer agents. The diuretic drugs and beta-blockers remain excellent choices in the management of hypertension. PMID- 2577459 TI - Antihypertensive drug therapy and survival by treatment status in a national survey. AB - The National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study, an investigation of a cohort originally examined during the period 1971-1975, provided an opportunity to assess the frequency of antihypertensive drug therapy in the United States during the period 1982-1984. For most age-sex-race subgroups, the frequency of medication use during 1982-1984 was higher than that observed during 1976-1980 based on the NHANES II. In the interval 1982-1984, diuretic agents were the most frequent medications prescribed (47% of drugs prescribed), and beta-blockers were second (17%). At the time of the initial survey in 1971-1975, participants had their blood pressures measured and a history of diagnosis and treatment of hypertension ascertained. Follow-up for vital status was 93% complete by 1984 (average length of follow-up, 9 years). In white men and women aged 50 years and older, the relative risk of death increased steadily, from those with elevated blood pressure (systolic blood pressure greater than or equal to 160 mm Hg or diastolic blood pressure greater than or equal to 95 mm Hg) but no history of hypertension to those treated for hypertension but whose blood pressure was still elevated. Regardless of history or treatment, those with an elevated blood pressure had about a 25-30% excess risk of death. Evidence from these national studies shows a high frequency of antihypertensive drug therapy in 1982-1984 and suggests the importance of adequate blood pressure control for optimal survival. PMID- 2577460 TI - Diuretic agents versus beta-blockers. Comparison of effects on mortality, stroke, and coronary events. AB - Three recently concluded large randomized clinical trials have compared the preventive effects of diuretic agents and beta-blockers in the treatment of approximately 22,000 subjects with hypertension. In the Medical Research Council trial, bendrofluazide (10 mg daily) was compared with a dose of propranolol (as much as 240 mg daily), a nonselective beta-blocker without intrinsic sympathomimetic activity. Two selective beta-blockers, atenolol (100 mg daily) and metoprolol (200 mg daily), were compared with bendrofluazide (5-10 mg daily) and hydrochlorothiazide (50-100 mg daily) in the Heart Attack Primary Prevention in Hypertension trial. In the International Prospective Primary Prevention Study in Hypertension, 160 mg of slow-release oxprenolol, a beta-blocker with intrinsic sympathomimetic activity, was compared with a diuretic-based regimen not containing beta-blockers. In each trial, similar reductions in mean diastolic blood pressure were achieved with diuretic and beta-blocker treatment that lasted for several years. All-cause mortality and fatal and nonfatal stroke and coronary event rates were also similar in the treatment groups. Thus, it appears that beta blockers are as effective as diuretic agents in improving survival and in preventing major morbid events. Regarding cigarette smoking and stroke incidence, observations based on post hoc subgroup analyses of the Medical Research Council trial were not supported by subgroup findings in the Heart Attack Primary Prevention in Hypertension and the International Prospective Primary Prevention Study in Hypertension trials, and these observations should not form the basis for any treatment recommendations. PMID- 2577461 TI - Diuretic agents and beta-blockers in the treatment of hypertension. AB - Benzothiadiazine diuretic agents and beta-adrenergic receptor-blocking drugs are two of the main groups of drugs used to treat mild hypertension. Recently, questions have been raised about their relative efficacy in preventing morbidity and mortality from vascular disease in addition to their effect on lowering blood pressure. Attention has been focused on the unfavorable metabolic effects of diuretic drugs and the proven value of beta-adrenergic receptor blockade in secondary prevention after myocardial infarction. Four randomized controlled trials comparing drugs in these two classes have been published: the Medical Research Council trial, the International Prospective Primary Prevention Study in Hypertension, the Heart Attack Primary Prevention in Hypertension trial, and the Metoprolol Atherosclerosis Prevention in Hypertension study. These trials, especially that of the Medical Research Council, have raised some questions about the relative efficacy of these two classes of drugs in preventing stroke in smokers and nonsmokers. Overall, there is little evidence of a reduction in morbidity and mortality after myocardial infarction. The predicted advantage of beta-adrenergic receptor blockade over diuretic therapy has not been realized although there are sufficient hints of a differential benefit to encourage the performance of further trials. PMID- 2577462 TI - [First Scientific Meeting of Medicine and Surgery Departments: Parma- Semmelweis]. PMID- 2577463 TI - [Gamma-glutamyltranspeptidase activity and glutathione content in the mammary gland during the processes of pregnancy and lactation in chronically malnourished rats]. AB - The influence of early and chronically dietary protein and energy restriction on gamma glutamyl transpeptidase (GGTP: E.C.2.3.2.2.) activity of the mammary gland of pregnant and lactating rats, was studied. Rats fed a restricted amount of a 25% casein diet throughout gestation and lactation decreased mammary gland weight, DNA, and protein content. The GGTP activity in the mammary gland of the malnourished group was significantly decreased during all of the experimental trial period, and a decrease of offspring weight gain was also observed in that group. The inhibition of GGTP activity in the mammary gland caused by effects of maternal protein and energy undernutrition, could have depressed mammary uptake of amino acids, suggesting a reduced milk protein content and/or milk output. PMID- 2577465 TI - Hong Kong-Canadian Conference of Gastroenterology and Hepatology. Hong Kong, 30 November-3 December 1989. Abstracts. PMID- 2577464 TI - Gastrin and somatostatin cells in dyspeptic patients with and without duodenal ulcer: a quantitative study based on multiple biopsy specimens. AB - The numbers of immunoreactive gastrin and somatostatin cells in gastric and duodenal mucosal biopsy specimens from dyspeptic patients with duodenal ulcers and dyspeptic controls without ulcers were calculated using a morphometric method. The levels of gastrin and somatostatin in the tissue were also measured by the radioimmunoassay. The results showed no significant difference in the number of G cells and the level of gastrin in the tissue between the ulcer and non-ulcer groups. However, the number of D cells and the level of somatostatin in the tissue in ulcer patients were remarkably reduced in comparison with those in non-ulcer patients (P less than 0.01 and P less than 0.05, respectively). The G:D cells and gastrin:somatostatin ratios in ulcer patients were much higher than those in the non-ulcer control group. It is considered that the reduction of D cells and the relative lack of somatostatin in duodenal ulcer patients might have a role in the mechanism of the duodenal ulceration. PMID- 2577466 TI - WHO's European member states look at quality assurance. Report on the technical discussions at the thirty-eighth session of the Regional Committee for Europe. AB - This paper is the report on the technical discussions on "Quality assurance of health services" at the 38th session of the WHO Regional Committee for Europe, one of the activities aiming at achieving WHO's regional health for all target 31, which requests WHO's Member States to establish a quality assurance mechanism. Attended by national health authorities and experts in quality assurance, the technical discussions identified the European context for developing quality assurance and looked at national initiatives. Having agreed that the question is no more, "Is there a need for quality assurance of health services?" but, "How can it best be carried out?", the participants identified a range of quality assurance activities at national and international levels, including national strategies and financial incentives, criteria for clinical practice, information systems and coordination and management mechanisms. The report concludes with recommendations for Member States on, for example, inclusion of quality assurance in national health policies, dissemination of information, research on quality assurance, information systems and role of professional organizations. PMID- 2577467 TI - [Soldering of a low gold content alloy (46%)]. AB - This is the third part of a research about a low gold content alloy (Au 46%, Pd 4%, Ag 40%, Cu and Zn), involving the study of soldered joints. Transverse test was used to evaluate mechanical resistance of bars joined by soldering. Comparativily were considered the following "soldering" condution: entire bars without investing and without soldering; entire bars with investing and without soldering but simulating thermal cycle and quenched in water after one and five minutes; with investing, soldering and quenched in water after one and five minutes. Of the "soldered" alloy were obtained also Brinell and Vickers hardness numbers. Corrosion resistance test was performed for six month at vapors of acetic acid solution, saturated with hydrogen sulfide. From the results it was possible to conclude: the soldered joints of the alloy reach good corrosion resistance; the soldered joints do not become brittle; thermal cycling as elapsed from soldering procedure and water quenched after five minutes increases the strength of the alloy and the soldered joints. PMID- 2577468 TI - Detection of DNA sequence polymorphisms by enzymatic amplification and direct genomic sequencing. AB - The discovery of RFLPs and their utilization as genetic markers has revolutionized research in human molecular genetics. However, only a fraction of the DNA sequence polymorphisms in the human genome affect the length of a restriction fragment and hence result in an RFLP. Polymorphisms that are not detected as RFLPs are typically passed over in the screening process though they represent a potentially important source of informative genetic markers. We have used a rapid method for the detection of naturally occurring DNA sequence variations that is based on enzymatic amplification and direct sequencing of genomic DNA. This approach can detect essentially all useful sequence variations within the region screened. We demonstrate the feasibility of the technique by applying it to the human retinoblastoma susceptibility locus. We screened 3,712 bp of genomic DNA from each of nine individuals and found four DNA sequence polymorphisms. At least one of these DNA sequence polymorphisms was informative in each of three families with hereditary retinoblastoma that were not informative with any of the known RFLPs at this locus. We believe that direct sequencing is a reasonable alternative to other methods of screening for DNA sequence polymorphisms and that it represents a step forward for obtaining informative markers at well-characterized loci that have been minimally informative in the past. PMID- 2577470 TI - Parental origin of the extra chromosome in trisomy 18. AB - The parental origin of the supernumerary chromosome 18 was investigated by RFLP analysis in 23 individuals with Edwards syndrome. All families were studied with the DNA probe pERT-25, which recognizes a locus of highly polymorphic tandemly repeated DNA sequences on chromosome 18. The extra chromosome was found to be of maternal origin in 19 patients (95%), of paternal origin in one patient (5%), and indeterminate in three patients. In one of the three indeterminate cases, a mosaic, an apparent recombination event had taken place within the pERT-25 locus. The overall high degree of informativeness of pERT-25 illustrates the power of a chromosome-specific variable-number tandem repeat probe (VNTR) in parental origin studies of aneuploidy. PMID- 2577471 TI - Recent advances in molecular biology of childhood and adolescent gynecologic disorders. PMID- 2577472 TI - Applications of molecular genetics to gastrointestinal and liver diseases. II. Clinical relevance. AB - The use of DNA probes within or near disease genes is becoming increasingly important in clinical medicine. Probes are available for prenatal and carrier diagnosis for several of the more than 100 genetic diseases of the gastrointestinal tract and liver. These include familial adenomatous polyposis, haemochromatosis, cystic fibrosis, alpha 1-antitrypsin deficiency and the hereditary porphyrias. This review uses examples drawn from such diseases to show the relevance of these approaches to the clinician. PMID- 2577473 TI - [Panarteritis nodosa and hepatic involvement]. PMID- 2577469 TI - Localization of HeLa cell tumor-suppressor gene to the long arm of chromosome II. AB - Cytogenetic and molecular genetic analyses of human intraspecific HeLa x fibroblast hybrids have provided evidence for the presence of a tumor-suppressor gene(s) on chromosome 11 of normal cells. In the present study, we have carried out extensive RFLP analysis of various nontumorigenic and tumorigenic hybrids with at least 50 different chromosome 11-specific probes to determine the precise location of this tumor-suppressor gene(s). Two different hybrid systems, (1) microcell hybrids derived by the transfer of a normal chromosome 11 into a tumorigenic HeLa-derived hybrid cell and (2) somatic cell hybrids derived by the fusion of the HeLa (D98OR) cells to a retinoblastoma (Y79) cell line, were particularly informative. The analysis showed that all but one of the nontumorigenic hybrid cell lines contained a complete copy of the normal chromosome 11. This variant hybrid contained a segment of the long arm but had lost the entire short arm of the chromosome. The tumorigenic microcell and somatic cell hybrids had retained the short arm of the chromosome but had lost at least the q13-23 region of the chromosome. Thus, these results showed a perfect correlation between the presence of the long arm of chromosome 11 and the suppression of the tumorigenic phenotype. We conclude therefore that the gene(s) involved in the suppression of the HeLa cell tumors is localized to the long arm (q arm) of chromosome 11. PMID- 2577474 TI - Effect of somatostatin-14 on gastric emptying and on gastrin and insulin release after ingestion of a mixed solid-liquid meal in man. AB - The effect of somatostatin-14 on gastric emptying, as well as on serum concentrations of gastrin, insulin, glucose, calcium, and phosphorus after ingestion of a mixed solid-liquid meal was examined in seven healthy men in a double-blind placebo-controlled study. An i.v. bolus injection of 61 nmol somatostatin was followed by 244 nmol infused at a constant rate over 90 minutes. Gastric emptying of a radiolabelled meal was surveyed with the use of a gamma camera. A weak delaying effect of somatostatin on gastric emptying of a solid meal did not prove to be statistically significant. Somatostatin decreased significantly the postprandial gastrin release: the area under the gastrin curve, AUC0-90, 9954 +/- 2287 ng.l-1 min (placebo) vs 5327 +/- 718 ng.l-1 min (somatostatin), p less than 0.05. At the same time suppression of the postprandial insulin release by somatostatin was observed--area under the insulin curve, AUC0-90, 1450 +/- 161 mU.l-1 min (placebo) vs 501 +/- 60 mU.l-1 min (somatostatin), p less than 0.002. The postprandial increase in serum glucose concentration was initially attenuated, and shifted towards the end of somatostatin infusion, when referred to the placebo situation. Somatostatin did not change significantly the serum calcium or phosphorus concentrations. The results obtained indicate that somatostatin's effect on gastric evacuation is less pronounced in contrast to the significant inhibitory influence of somatostatin on release of gastrointestinal hormones. PMID- 2577475 TI - Alpha interferon treatment in HIV infected patients restores gamma interferon production in vitro. AB - We studied gamma interferon (IFN) production in vitro by lymphocytes from 5 patients with AIDS and 2 with advanced AIDS-related complex (ARC) before and during treatment with r-alpha 2a IFN at low doses, for up to 12 months. Patients were divided in responders (three) and non responders according to clinical data after six months of treatment. No immunological parameter was predictive of the clinical results. We found that subpopulations of T lymphocytes and lymphoproliferative response were not significantly modified in responders, while severely decreased in non responder patients. In 5/7 cases we observed a small but significant increase of gamma IFN production after six months of therapy, which rose to normal values after 12 months in responders. PMID- 2577476 TI - [Prevalence of anti-HIV-2 antibodies in a population at risk attending the drug dependence center of the Rho hospital]. AB - We have evaluated the prevalence of anti HIV-2 antibodies in a population of 139 individuals at risk for AIDS, attending the center for drug addiction of the Rho hospital. 79.85% of our patients were positive for anti HIV-1 antibodies. 51 patients (36.69%) were positive for anti HIV-2 antibodies in an immunoenzymatic method, but only 16 patient (11.51%) have been confirmed in Western Blot. We stress, therefore, the necessity of confirming the positivity for anti HIV-2 antibodies with the Western Blotting method. 14.41% of our anti HIV-1 positive patients were also anti HIV-2 positive, but no one showed an isolate positivity for anti HIV-2 antibodies. PMID- 2577477 TI - Restriction map of large plasmid pFW1 in Bacillus sphaericus strain 10. AB - Some strains of Bacillus sphaericus have been found to be toxic to mosquito larvae (1). They differ from Bacillus thuringiensis var. israelensis (BTI) (2,3) in the following aspects: BTI is relatively ineffective in polluted water, and its residual activity in most habitats is limited to a few days after treatment, whereas BS isolates are effective in such habitats, particularly against species of Culex; BS also remains effective longer, as a result of either persistence or recycling. B. sphaericus strain 10 (BS10) was isolated by the Lixiahe Institute of Agricultural Sciences in Jiangsu Province. Its larvicidal activity is much higher than that of BS1593, which was recommended by the World Health Organization for widespread use as a standard strain (1). The mosquito-larvicide gene of BS1593 has been cloned and expressed in E. coli and B. subtilis (4, 5). In the present study, BS10 was investigated to establish whether it contains the plasmid and whether homology exists between the mosquito-larvicide gene in BS and that in BTI. PMID- 2577478 TI - Omeprazole in acute and long-term treatment of Asian patients with peptic ulcer refractory to H2-antagonists. AB - Twenty-seven patients with peptic ulcer (19 with duodenal ulcer (DU) and eight with gastric ulcer (GU] refractory to H2-antagonists were treated with 40 mg of omeprazole once daily for 4-8 weeks, depending on the rate of ulcer healing. Clinical assessment, endoscopy and laboratory tests were performed at entry, after 2 and after 4 weeks, and if unhealed, also after 8 weeks' treatment. Ten healed patients were given a maintenance therapy of omeprazole 20 mg daily for up to 12 months during which the patients returned for endoscopy, gastric biopsy and laboratory tests at 3-monthly intervals. The initial treatment healed 15 of 19 (79%) DU patients in 2 weeks and all DU patients by 4 weeks. Seven of eight (87%) GU patients healed in 4 weeks and only one required 8 weeks' treatment. Symptom relief was rapid, with most patients being symptom-free within the first day of treatment. Six patients received 12 months' continuous maintenance therapy, one patient 9 months and three patients 6 months' treatment. All patients remained in remission whilst on omeprazole therapy. No adverse events were reported throughout the study. There were no clinically significant changes in haematology or blood chemistry after healing or during the long-term treatment. Biopsy samples revealed no histological changes in the gastric mucosa at any stage. Omeprazole 40 mg therefore was found to produce rapid healing and symptom relief in Asian patients with H2-antagonist-resistant peptic ulcers. Maintenance therapy with omeprazole 20 mg daily was shown to be safe and effective in preventing recurrence of peptic ulceration. PMID- 2577479 TI - [CD4+ and CD8+ lymphocyte subpopulations in bone marrow deficiency anemias]. AB - The study of CD4-CD8 lymphocytary sub-populations in 13 anaemic patients led the authors to note an increase in the CD8+ population in 61.5% of the cases, which resulted in the inversion of their CD4/CD8 ratio. This increase in the CD8 sub population is connected with marrow-deficient anaemia, which leads them to suggest that marrow-deficient anaemia could well be classified according to the lymphocytary sub-populations. PMID- 2577480 TI - The use of single locus and multilocus minisatellite probes to diagnose specific individuality. PMID- 2577481 TI - [Milan, 15-21 July 1990, the Second World Congress on Surgery and Surgical and Oncological Disciplines at the University of Milano]. PMID- 2577482 TI - Determining the optimal dosage regimen for H2-receptor antagonist therapy--a dose validation approach. AB - A large number of clinical studies have been performed to establish the safety and efficacy of H2-receptor antagonist therapy. Few if any of these studies have attempted to address the rationale for the dosage and/or dosage regimens being studied. This study is the first large-scale clinical trial, the purpose of which is to validate the chosen regimen and to address the issue of an optimal therapy for a specific patient population. A regimen of a single nightly dosage is generally acknowledged to offer the potential for improved patient compliance. Furthermore, recent research had suggested that suppression of nocturnal acid secretion is all that is required to heal duodenal ulcers. Hence such a regimen offered the potential for an effective lowered dosage of cimetidine with minimal interference with gastric physiology, increased safety and substantial efficacy. This multicentre, double-blind, placebo-controlled trial therefore evaluated a 4 week course of single night-time dosage of cimetidine. After 4 weeks of treatment the cumulative, endoscopically proven, ulcer healing rate with an 800 mg regimen was 73%, which was statistically higher and significantly superior to the 41% healing seen with placebo (P less than 0.001). The 400 mg nocte dosage regimen of cimetidine normally used as maintenance therapy was significantly inferior to the 800 mg nocte regimen (P = 0.01), and increasing the dosage to 1600 mg nocte for 4 weeks failed to provide a significant improvement in healing over the 800 mg nocte regimen. This 800 mg nocte regimen provided rapid pain relief, with 75% of the patients being free of night-time pain and 65% free of day-time pain, by the end of the first week. The 400 mg 'maintenance dosage' was unable to provide this degree of rapid, complete and early relief to patients with a duodenal ulcer. Furthermore, increasing the dosage to 1600 mg nocte failed to increase the level of early pain relief significantly, perhaps because the extensive response of duodenal ulcer patients to the 800 mg nocte regimen leaves little room for improvement. Based both on the early symptom relief and the ulcer healing rate during 4 weeks of treatment, it is concluded that an 800 mg night-time dosage of cimetidine may be an optimal regimen for many duodenal ulcer patients, particularly those who in the physician's opinion will benefit from a once-daily regimen. PMID- 2577483 TI - Comparative efficacy of coated, oral 5-aminosalicylic acid (Claversal) and sulphasalazine for maintaining remission of ulcerative colitis. International Study Group. AB - The safety and efficacy of Claversal (coated, oral 5-aminosalicylic acid (5-ASA) 0.75 g/day) and sulphasalazine 1.5-2.0 g/day were compared for the maintenance treatment of ulcerative colitis in a 1-year double-blind trial. Three hundred and thirty-four patients, whose disease was controlled on a stable dose of sulphasalazine (1.5-2.0 g/day) for a 1-month pre-trial, entered the study. On entry, patients were assigned in a random manner to continue sulphasalazine or to switch to coated 5-ASA. One hundred and thirty-one patients in the coated 5-ASA group and 142 on sulphasalazine were analysed for efficacy. No significant difference was observed between treatments with respect to the cumulative rate of relapse. Over the 12 months, 30 (28%) of the coated 5-ASA patients versus 29 (23%) of those treated with sulphasalazine had an exacerbation of their disease (log rank test P = 0.7011). The incidence of drug-related adverse events and subsequent withdrawals was similar. The high incidence of side-effects usually associated with sulphasalazine was not observed, probably due to the fact that this population was tolerant of sulphasalazine pre-trial. Of the 37 patients who reported adverse events with previous sulphasalazine therapy, however, only two (8%) of the 24 experienced those events when randomized to coated 5-ASA while five (38%) of the 13 who continued on sulphasalazine reported those same events. Coated 5-ASA is a safe, effective therapy for maintaining ulcerative colitis in remission. PMID- 2577484 TI - [MEN I (multiple endocrine neoplasia): patient screening and new tumor markers]. AB - Multiple endocrine neoplasia type I (men I) associates hyperparathyroidism with pancreatic tumors. The evaluation included the patient and its family, periodically. A good patient medical history, biochemical blood tests, carried out regularly and in an organised fashion, brings to the fore the diagnosis without difficulties. Tumoral markers are now being considered an important test for diagnosis and follow-up (gastrin, pancreatic peptid, prolactin...). The newest chromogranin is a polypeptidic group which increases in the blood of patients with endocrine neoplasias (including hyperparathyroidism and tumors of pancreatic islet cells). The specific neural enolase is increase in pancreatic islet cells tumor. The evaluation of S-100 substance, 7-B2 protein, neurotensin, alpha sub-unit of chorionic gonadothrophin and other markers will soon be of help in the diagnosis of men I. PMID- 2577485 TI - Second International Workshop on Cytokines. Hilton Head Island, South Carolina, December 101-4, 1989. Program and abstracts. PMID- 2577486 TI - [Nodular regenerative hyperplasia of the liver associated with a CREST syndrome with multiorgan involvement]. AB - A 52 year old woman with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal hypomotility and telangiectasia) and visceral involvement of the kidneys, lungs and liver is presented. The hepatic implication was a focal nodular hyperplasia of the liver which is a component not frequently recognized. Another 4 cases of this syndrome, associated to different forms of scleroderma, were described previously. Because of the way in which this case developed, this disease should be suspected when alkaline phosphatase and gamma glutamyltranspeptidase levels are elevated. We comment on the utility of the laparoscopy and liver biopsy in diagnosing the diseased and the situation found. Finally, we discuss the pathogenic implications of the disease with scleroderma, owing to the vascular mechanism. PMID- 2577487 TI - [Prenatal diagnosis: molecular basis and techniques used in the diagnosis of monogenic hereditary diseases]. PMID- 2577488 TI - [Prolonged febrile syndrome. A presentation + form of Takayasu's arteritis]. PMID- 2577489 TI - [A quantitative study of the consumption of antihypertensives in Management Area 5 of the ICS (Costa de Ponent). Institut Catala de la Salut]. AB - The use of antihypertensive drugs (AHD) in the area n degrees 5 of the Institut Catala de la Salut was evaluated for the period October 1986-December 1987. The unit of measure was the DDD (daily defined dose) per 1,000 population individuals per day. The overall use of AHD in 1987 was 49.31 DDDs/1,000 individuals/day; it was distributed among diuretics (53.5% of all AHD), beta-blockers (11.3%), and other AHD (35.2%). The most commonly prescribed drugs, by decreasing frequency order, were combinations of low ceiling diuretics with potassium sparing drugs, and of rauwolfia alkaloids with diuretics, followed by nifedipine, chlortalidone and furosemide. The interannual evaluation disclosed an increase of 18.6% in 1987 as compared with the preceding year, mostly at the expense of beta-blockers. On the other hand, there was a tendency to refrain from the use of fixed dose drug associations. This is a criterion of better use of antihypertensive therapy. PMID- 2577490 TI - Lack of effect of methimazole on thyrocyte cell-surface antigen expression. AB - The nature of the immunosuppressive effect of antithyroid drugs has been a subject of controversy. It has been claimed that these agents exert a direct effect on the immune system, although we and others have suggested that the drugs affect the thyroid cells primarily with consequent reduced thyrocyte-immunocyte signalling. This may occur from reduced thyroid hormone production and/or reduced antigen presentation by the thyrocytes to local T lymphocytes. Using a cytotoxicity assay system, with chromium-51 labelling, monoclonal antibodies against thyroperoxidase (TPO) and HLA-DR, and complement, we have measured the expression of TPO and HLA-DR on cultured normal human thyroid cells; we have also measured thyroglobulin (Tg) release by radioimmunoassay into the medium of the cultured cells. The thyroid cells were stimulated with TSH or thyrotropin binding inhibitory immunoglobulin (TBII) for 48 hours before measuring for TPO induction, and with interferon gamma (IFN-gamma) (with or without TSH or TBII) for thyrocyte HLA-DR expression. A dosage of 1.6 milliunits per ml of TSH resulted in a significant increase in TPO expression on thyrocytes when compared with control unstimulated thyroid cells (p less than 0.001). The concentrations of Tg released into the medium with TSH or TBII were also significantly higher than those of the control thyrocytes. IFN-gamma at 200 units per ml induced HLA-DR expression, but did not induce thyrocyte TPO expression, or Tg release. Addition of the antithyroid drug, methimazole (MMI), at different concentrations, in addition to the other stimulators, IFN-gamma, TSH, or TBII, did not result in any inhibition of TPO, Tg release, or HLA-DR expression on the thyroid cells. It would thus appear that the pathways for stimulation for the expression of TPO and HLA-DR appear to be different. Finally, MMI does not cause its immunosuppressive effect by any reduction of thyroid antigen expression or release. PMID- 2577491 TI - Assays of TSH-receptor antibodies in 576 patients with various thyroid disorders: their incidence, significance and clinical usefulness. AB - The incidence and the significance of TSH-receptor antibodies in Graves' disease and in various thyroid disorders have been evaluated. TSH-binding inhibiting antibodies (TBIAb) and thyroid stimulating antibodies (TSAb) were detected in a large proportion of Graves' disease patients (TBIAb in 68.8% and TSAb in 77.8%), in a small number of patients with idiopathic myxoedema or Hashimoto's thyroiditis, and were not detected in patients with endemic euthyroid goitre, differentiated thyroid carcinoma and toxic adenoma. Furthermore, TSH-receptor antibodies were present in some patients with toxic multinodular goitre (TBIAb in 12.7% and TSAb in 15.9%). When TSH-receptor and other thyroid autoantibodies were compared, it was found that 13 of the 15 Graves' patients with negative tests for thyroglobulin and thyroid microsomal antibodies were positive for TSH-receptor antibodies. On the other hand, 9 of the 11 patients with toxic multinodular goitre who had positive TSH-receptor antibody tests, also had serum thyroglobulin and/or thyroid microsomal antibodies. No significant differences in the prevalence of TSH-receptor antibodies were found in Graves' patients irrespective of the presence of ophthalmopathy or pretibial myxoedema. Elevated TBIAb activity at the end of anti-thyroid drug treatment was found in 52.9% of Graves' patients who subsequently relapsed, while in Graves' patients in remission TBIAb was always negative. TSH-receptor antibody results were not predictive of the outcome of radioiodine treatment in Graves' disease. Finally no correlation could be found between TBIAb and TSAb in Graves' disease and Hashimoto's thyroiditis. IN CONCLUSION: the high incidence of TSH-receptor antibodies in Graves' disease confirms their pathogenetic role in the development of hyperthyroidism; TSH receptor antibodies in Graves' disease are not significantly associated with the presence of ophthalmopathy or pretibial myxoedema; TSH-receptor antibody assays may be useful for the diagnosis of Graves' disease in the absence of other signs of autoimmunity. TBIAb seems to be a good predictor of relapse in Graves' patients treated with anti-thyroid drugs; a fraction of toxic multinodular goitre could be a nodular variant of Graves' disease. PMID- 2577492 TI - Derivation of non-lymphopenic BB rats with an intercross breeding. AB - Previous studies have suggested that the development of diabetes in the BB rats does not require the expression of T lymphopenia. In order to derive non lymphopenic diabetic rats and define the relationship between the T cell abnormalities, MHC genotype, and diabetes, we performed a cross between BB/H and diabetes resistant BB/control followed by an intercross of the F1. In the F2, the overall incidence of diabetes and lymphopenia was 30% and 27%, respectively. Lymphopenia was strongly associated with diabetes (p less than 0.001) and was seen in 76% of the diabetic F2's. However, 6 of the diabetic were non-lymphopenic (24%) and 3 of the non-diabetics were lymphopenic (5%). In the non-lymphopenic diabetic animals, all T cell levels were within the normal range, but diabetes occurred at an earlier age than their lymphopenic littermates (p less than 0.001). In contrast to the strong association between the inheritance of lymphopenia and diabetes, no relationship between diabetes and Class I MHC restriction fragment length polymorphisms was found. We conclude: 1) Diabetes and lymphopenia are strongly associated inherited abnormalities in the BB rat and are not associated with Class I RFLP defined genotypes within the RTIu haplotype, 2) Animals in whom diabetes occurs in the absence of lymphopenia can be derived using this breeding approach 3) In our non-lymphopenic rats, diabetes occurred at an earlier age possibly reflecting the restoration of quantitative or qualitative T cell defects found in lymphopenic BB rats. PMID- 2577493 TI - The major histocompatibility complex and insulin dependent (type 1) diabetes. AB - The majority of the genetic component in insulin dependent (Type 1) diabetes mellitus can be explained by associations with genes on short arm of chromosome 6 located in the major histocompatibility complex. With the advent of cloning of the HLA Class II region genes it has been possible to refine the previous known association of HLA-DR3 and DR4 with this disease. Strong associations of IDDM have now been shown to exist with the DQB1 gene and/or linked genes, although this does not completely explain the HLA susceptibility to this disease. PMID- 2577494 TI - Lymphokines in inflammation. PMID- 2577496 TI - Cloning and nucleotide sequence of the alpha-galactosidase cDNA from Cyamopsis tetragonoloba (guar). AB - Polyadenylated mRNA was purified from the aleurone cells of Cyamopsis tetragonoloba (guar) seeds germinated for 18 h and used for the construction of a cDNA library. Clones with the alpha-galactosidase encoding gene were identified using oligo-nucleotide mixed probes based on the NH2 terminal amino acid sequence and on the sequence of an internal peptide. The nucleotide sequence of the cDNA clone showed that the enzyme is synthesized as a precursor with a 47 amino acid NH2 terminal extension. This pre-sequence most likely functions to target the protein outside the aleurone cells into the endosperm. Based upon structural features, it is proposed to divide the precursor into a pre-(signal sequence) part and a glycosylated pro-part comparable with those of the yeast mat A/alpha factor and killer factor. A comparison of the derived amino acid sequence of this alpha-galactosidase from plant origin revealed significant stretches of homology with respect to the amino acid sequences of the enzymes from Saccharomyces cerevisiae and from human origin but only to a minor extent compared with the alpha-galactosidase from Escherichia coli. PMID- 2577495 TI - The isolation and characterization of a cDNA clone encoding Lupinus angustifolius root nodule glutamine synthetase. AB - Glutamine synthetase, purified from Lupinus angustifolius legume nodules, was carboxymethylated and succinylated prior to chemical or enzymatic cleavage. Peptides were purified and sequenced. An oligonucleotide probe was constructed for the sequence MPGQW. This probe was used to identify a glutamine synthetase cDNA clone, pGS5, from a lupin nodule cDNA library constructed in pBR322. pGS5 was sequenced (1043 bp) and computer-assisted homology searching revealed a high degree of conservation between this lupin partial cDNA clone and other plant glutamine synthetases at both the amino acid (greater than 90%) and nucleotide (greater than 80%) level. Northern and Southern analyses using pGS5 supported the conclusion that a multigene glutamine synthetase family exists in lupin which is differentially expressed in both an organ-specific and temporal manner. Western and Northern blot analyses indicated the accumulation of a glutamine synthetase specific mRNA species during nodule development corresponded to the appearance of a novel glutamine synthetase polypeptide between 8 and 10 days after rhizobial inoculation. PMID- 2577497 TI - Three cDNA sequences coding for glutamine synthetase polypeptides in Oryza sativa L. PMID- 2577498 TI - Can higher doses of an H2-receptor antagonist accelerate duodenal ulcer healing? AB - Drugs that inhibit gastric acid secretion heal duodenal ulcers at a rate that correlates with the ability of individual treatment regimens to decrease 24-h intragastric acidity. As current therapeutic regimens of ranitidine decrease 24-h intragastric acidity submaximally, higher dosages may expedite duodenal ulcer healing. To test this hypothesis a randomized, double-blind clinical trial was conducted in 245 patients with duodenal ulcer to compare the effects of standard dose (300 mg nocte) and high-dose (300 mg q.d.s.) ranitidine. Patients were assessed after 2 weeks of treatment and, if unhealed, after a further 2 weeks of therapy. The therapeutic gain in ulcer healing at the 2-week endoscopy of the higher dose over the lower dose of ranitidine was 22% (68% vs 46%, P less than 0.001). The cumulative ulcer healing rates at the 4-week endoscopy were 88% and 92% for the standard and high-dose ranitidine groups, respectively (N.S.). By 2 weeks, 61% of patients treated with standard ranitidine therapy and 79% of those receiving 300 mg ranitidine q.d.s. were pain-free (P less than 0.01). A further 2 weeks of therapy enabled 88% and 97% of patients (N.S.) to become pain-free on these two regimens, respectively. The drug regimens were equally well tolerated. Thus higher-dose ranitidine can significantly accelerate the healing of duodenal ulcer with improvement in pain relief. PMID- 2577499 TI - The effect of a new selective alpha 2-adrenoreceptor antagonist, idazoxan, and the agonist, clonidine, on fasting antroduodenal motility in healthy volunteers. AB - Studies were carried out on 16 healthy male volunteers to investigate whether intravenous administration of the alpha 2-adrenoreceptor antagonist, idazoxan, could affect fasting antroduodenal motility with and without administration of the agonist, clonidine. Contractile activity was recorded using an oral tube with perfused side holes positioned in the stomach and duodenum. Clonidine decreased antral contractile activity, an effect that idazoxan did not restore. Idazoxan alone did not affect antral motility. In the duodenum, clonidine decreased the number of contractions significantly and idazoxan restored them. Idazoxan alone did not increase duodenal motility but clonidine induced phase-III activity within the first 15 min after administration. The observations indicate that regulation of antroduodenal motility is influenced by alpha 2-adrenoreceptor drugs. Idazoxan may have potential as a motility restoring drug, for example, in postoperative ileus. PMID- 2577500 TI - The effect of SK&F 94482 (BMY-25368) on 24-hour intragastric acidity and plasma gastrin concentration in healthy subjects. AB - In a double-blind, placebo-controlled study of SK&F 94482 (BMY-25368) (400-mg, post-evening meal, for 7 days in 11 healthy subjects), there was a significant 75% decrease in median integrated 24-h intragastric acidity during dosing with the drug (218 mmol h/L) compared with placebo (883 mmol h/L; P = 0.003). The single daily dose of 400 mg SK&F 94482 decreased median hourly intragastric acidity until the time of the next dose 24 h later. There was also a sustained and significant 80% rise in median 24-h integrated plasma-gastrin concentration during dosing with SK&F 94482 (364 pmol h/L) when compared with placebo (202 pmol h/L; P = 0.003). The study demonstrates a significant inverse correlation between 24-h integrated intragastric acidity and 24-h plasma gastrin concentration (rs = 0.484; P less than 0.001). The study shows that a single oral daily dose of an H2 antagonist can provide control of intragastric acidity throughout the day and night, decreased acidity being associated with statistically significantly, but modestly elevated plasma-gastrin levels. PMID- 2577501 TI - Mesalazine in childhood inflammatory bowel disease. AB - A study was undertaken in paediatric patients suffering from ulcerative, Crohn's or indeterminate colitis. This aimed to compare the occurrence and tolerance of side-effects arising during treatment with position-release mesalazine (Asacol) with those occurring during previous treatment with sulphasalazine (Salazopyrin). The drugs were used to maintain remission from colitis. The occurrence of adverse reactions was also monitored. Sixty-seven children were assessed for a period of 6 months; 45 of these children received mesalazine after previous treatment with sulphasalazine. The results show that the majority of patients were maintained in remission with either drug, but they reported a preference for position-release mesalazine with respect to ease and frequency of administration when compared to sulphasalazine. No serious adverse reactions arose during mesalazine treatment, compared with three such events during previous sulphasalazine treatment. PMID- 2577502 TI - [Primary health care in the British and Andalusian national services: similarities and discrepancies]. PMID- 2577503 TI - [Increase of gamma-glutamyl transpeptidase: an insufficient marker of alcoholism]. PMID- 2577504 TI - [Rheumatoid arthritis in primary care]. PMID- 2577505 TI - Proceedings of the international symposium on portal hypertension and digestive organs, Tokyo, 25 February 1989. PMID- 2577506 TI - Deletion analysis of the polyadenylation signal of a pea ribulose-1,5 bisphosphate carboxylase small-subunit gene. AB - The polyadenylation signal of a pea gene for the small subunit of ribulose-1,5 bisphosphate carboxylase/oxygenase (rbcS) has been analyzed by deletion mutagenesis and Ti plasmid-mediated gene transfer. Sequences between 6 and 137 bases upstream from the normal polyadenylation sites in this gene (bases -6 to 137) are required for functioning of these sites. In addition, bases -111 to -235 can affect 3' end formation by altering the pattern of 3' termini seen in various transcription units. Sequences between 37 and 95 bases upstream from a cryptic polyadenylation site in this gene [A. G. Hunt, DNA 7: 329-336 (1988)] are necessary for mRNA 3' end formation at this site. At least two different parts of the 3' region of this rbcS gene can serve as a downstream element for polyadenylation at the normal poly(A) addition sites in this gene. Our studies indicate that: 1. the upstream sequences required for polyadenylation in plants are different from those defined in mammalian RNA polymerase II transcription units; 2. sequences 100 or more bases upstream and downstream from poly(A) addition sites in this gene can affect poly(A) addition site choice; and 3. there are apparently redundant downstream elements for polyadenylation in this gene. PMID- 2577508 TI - Bisoprolol--another cardioselective beta blocker. PMID- 2577507 TI - Molecular analysis of the ADH1-Cm allele of maize. AB - The Adh1-Cm allele and each gene in the Adh1-FCm duplication have been cloned and restriction-mapped. Of the Cm allele 6 kb was sequenced. A single amino acid substitution of aspartate for tyrosine at residue 52 accounts for the altered enzymatic properties of the Cm protein. Comparison of the nucleotide sequence to that of Adh1-1F and Adh1-1S shows structural and restriction site polymorphisms in the 3' flanking DNA. Cm lacks the insertion sequence present in 1F and 1S and contains a complex sequence composed of two direct repeats and an inverted repeat. The two genes of the duplication allele have similar restriction maps to Cm and each other. PMID- 2577509 TI - Photoaffinity labeling of melanocyte-stimulating hormone receptors. PMID- 2577510 TI - Peripheral dopaminergic nerves. PMID- 2577511 TI - The pharmacology of alpha 1- and alpha 2-adrenoceptors: evidence for and against a further subdivision. PMID- 2577512 TI - Clinical pharmacology of anxiolytics and antidepressants: a psychopharmacological perspective. PMID- 2577513 TI - Traumatic dental injuries in children. 2. Treatment of injuries to permanent teeth. PMID- 2577514 TI - Management of traumatic tooth injuries. An overview. PMID- 2577515 TI - Immunoprotection of guinea pigs against experimental acute pyelonephritis after the administration of Escherichia coli purified fimbriae. AB - Experimental results of the present study evidenced the following aspects: a) the antigen, prepared from type I Escherichia coli purified fimbriae (H. 2946 strain), induced immunity at urinary tract level; b) the immunoprotection induced by oral vaccination with multiple doses of fimbriated antigen produced a significant decrease of acute pyelonephritis in newborn guinea pigs and at the same time, a local protection of the urinary tract; c) the immunoprophylaxis by vaccine prepared from fimbriae represents a preferential solution for urinary tract infections prevention in general and especially in children; d) the frequency distribution differences between "protected" and "non-protected" animals were evaluated by chi-square--test with YATES correction and proved to be statistically significant at probability levels. PMID- 2577516 TI - Preliminary field trials of personal protection against mosquitoes in The Gambia using deet or permethrin in soap, compared with other methods. PMID- 2577517 TI - A laboratory investigation of mosquito larval predation by Toxorhynchites moctezuma on Aedes aegypti. AB - 1. Functional responses of predatory Toxorhynchites moctezuma (Dyar & Knab) larvae feeding on Aedes aegypti (L.) larvae (Diptera: Culicidae) were found to be type II of Holling (1959) and Rogers (1972). 2. Estimates of searching rate were generally higher for later instar predators. The search rate of second instar predators declined as prey instar increased, but fourth instar Tx. moctezuma had the highest search rate for second instar Ae. aegypti. 3. Prey handling times were higher for early instar predators and late instar prey. 4. When presented with mixtures of two instars of Ae. aegypti, second instar Tx. moctezuma showed frequency independent selectivity for the early instars, whereas fourth instar predators showed frequency independent selectivity for the late instars of Ae. aegypti. There was no evidence of frequency dependent predation. Preferences appeared to be transitive. 5. Extended random predator equations, using parameters derived from the functional responses, did not adequately describe the outcome of predation in the prey mixture experiment, even when the possibility of optimal switching behaviour was accounted for. PMID- 2577518 TI - Oviposition habitat preferences of Toxorhynchites moctezuma mosquitoes in four types of tropical forest in Trinidad. AB - 1. Oviposition of the mosquito Toxorhynchites moctezuma Dyar & Knab was investigated in four types of tropical forest in Trinidad, West Indies, using surrogate and natural ovitraps. Larvae of Tx. moctezuma are obligate predators that might be useful for the biological control of Aedes aegypti (L). 2. Significantly more oviposition occurred in seasonal-deciduous forest than in either montane or evergreen-seasonal forest. 3. Oviposition in surrogate containers (black-painted polystyrene cups, 90 mm diameter) was compared with that occurring in typical natural containers (nutpots of Lecythis zapucajo Aublet). Surrogate ovipots were relatively insensitive indicators of oviposition activity, and would be an inefficient means of harvesting Tx. moctezuma eggs. 4. Implications for the collection, culture and mass release of Tx. moctezuma are discussed. PMID- 2577519 TI - Laboratory tests of the effects of p-cresol and 4-methylcyclohexanol on oviposition by three species of Toxorhynchites mosquitoes. AB - Laboratory experiments tested the effects of p-cresol or 4-methylcyclohexanol at concentrations of 1, 10 and 50 ppm, on oviposition by the mosquitoes Toxorhynchites brevipalpis Theobald, Tx. amboinensis (Doleschall) and Tx. splendens (Wiedemann). A 5 + 5 ppm mixture of the two chemicals was also tested. All three species laid significantly more eggs in cups containing p-cresol, whereas only Tx. brevipalpis and Tx. amboinensis responded similarly to 4 methylcycohexonol and to the mixture of both chemicals. Tx. brevipalpis was, to a relatively limited degree, the most responsive of the three species. Ancillary experiments indicated that the chemicals were acting as attractants, causing more females to fly to treated cups. No stimulant effects were detected either in terms of the proportion of females that initiated oviposition flight (after flying to the cups) or in terms of the number of looping flights executed prior to ejection of an egg. PMID- 2577520 TI - Identification of metabolites of 3,4-(methylenedioxy)methamphetamine in human urine. PMID- 2577521 TI - [3rd National Convention, Household Risks and Prevention. Pavia, 18-20 March, 1990]. PMID- 2577522 TI - [Usefulness of the GOT, GPT, and GGT parameters in determining the etiology of cirrhosis]. PMID- 2577523 TI - Inhibition of hepatic drug metabolism by phenothiazine tranquilizers: quantitative structure-activity relationships and selective inhibition of cytochrome P-450 isoform-specific activities. AB - Twelve phenothiazine tranquilizers were investigated for the capacity to inhibit rat hepatic microsomal cytochrome P-450 (P-450) isoform-specific drug oxidation in vitro. All congeners were substituted in the 2-(carbocyclic) and 10- (thiazinyl nitrogen of the thiazine ring) positions. Cytochrome P-450 PB-B mediated 7-pentylresorufin O-depentylase and P-450 BNF-B-mediated 7 ethylresorufin O-deethylase activities were effectively inhibited by most of the compounds. Structure-activity correlations revealed the apparent importance of the lipophilicity of the 2-substituent, and the negative effect of flexibility in the 10-position substituent, on anti-P-450 PB-B potency. On the other hand, inhibition of P-450 BNF-B activity was promoted by bulkiness and branching within the 10-substituent and the shape/bulk of the 2-group. From this analysis it is likely that the active site of P-450 PB-B is relatively small with at least one lipophilic region that may be involved in substrate and inhibitor binding. The active site of P-450 BNF-B is relatively large, and steric properties, rather than lipophilic character, appear to determine inhibition by phenothiazines. Derivatives with piperidinyl and piperazinyl ring systems in the 10-position were relatively active inhibitors of P-450 PCN-E (or an immunochemically related form of P-450) that catalyzes androst-4-ene-3,17-dione 6 beta-hydroxylation, and P-450 UT-A-mediated 16 alpha-hydroxylase activity. In contrast, steroid 7 alpha hydroxylation (P-450 UT-F) and N-nitrosodimethylamine N-demethylation (P-450j) were refractory to inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2577524 TI - Food restriction and short-term effects of aflatoxin B1 feeding on putative preneoplastic biochemical markers. AB - The susceptibility of experimental rats to Aflatoxin B1, a well known hepatocarcinogen, during chronic food restriction was studied, using a few putative preneoplastic biochemical markers. Gamma-Glutamyl transpeptidase was the most sensitive among the various enzymes studied, at the dose of 10 micrograms/day/100 gm body weight of Aflatoxin B1 fed over a period of three weeks after a twelve chronic food restriction in experimental rats. It was significantly elevated in the underfed untreated group, thus suggesting that preneoplastic changes may be precipitated during chronic undernutrition and carcinogen exposure. PMID- 2577525 TI - Increase of brain ammonia after microwave irradiation and its mechanism. AB - Microwave irradiation at 4kW for 0.4 sec applied to the heads of mice produced an increase in brain ammonia. This increase resulted from stimulated breakdown of glutamine initiated by microwave irradiation and proceeded until freezing of the brain. Two glutamine-related enzymes, in the brain, phosphate-dependent glutaminase (assayed in the presence of 200mM phosphate) and glutamine synthetase, were inactivated by microwave irradiation in a similar fashion. On the other hand, glutaminase activity in the presence of 10mM phosphate increased. This is considered to be a probable cause of the increase in brain ammonia. The increased 10mM-phosphate glutaminase activity remained stable in the precipitate fraction even after 5% Triton X-100 treatment. PMID- 2577526 TI - Esmolol for the treatment of hypercyanotic spells in infants with tetralogy of Fallot. PMID- 2577527 TI - [Proceedings of the 106th Meeting of the German Society of Surgery, 29 March- 1 April 1989]. PMID- 2577528 TI - [Effect of magnetic resonance tomography on therapy planning in incontinence after anal atresia]. AB - Five healthy children and 16 children, ages 6-17 years, who had been operated on for anorectal atresia underwent magnetic resonance (MR) imaging of the pelvis. The development of sphincter muscles and the location of the pulled-through intestine in relation to the sphincter muscles were evaluated by a muscle score. There was good correlation between MR muscle score and clinical continence score. MR imaging provides additional information for therapeutic management and surgical procedures to improve continence. PMID- 2577529 TI - [Value of intra-anal ultrasound study for structural analysis of the continence organ--initial results]. AB - Endorectal ultrasound gives a fairly precise anatomical view of the muscular components of the continence organ. The strength of the puborectalis and the external anal sphincter can be measured with an accuracy slightly under one millimeter and consistency can be gauged roughly. Another major use is for the diagnosis of pelvic, particularly retrorectal, processes such as abscesses, tumours or duplication. Short distances between ultrasound probe and process yield a high resolution. The procedure is quick and does not cause any radiation effects (as opposed to CT). PMID- 2577530 TI - [Quality of life as deciding criterion in routine practice and in research by the surgeon]. AB - Symptoms and their effects on quality of life are reasons for the patient to consult the physician. They are the basis for active treatment, choice of therapeutic concepts and evaluation of success. However, quality of live parameters are rarely used and accepted as relevant endpoints to be determined after surgical interventions. 5 typical clinical situations demonstrate that only evaluating different dimensions of quality of life parameters can help to examine the success of surgical interventions. It is therefore emphasized that such parameters should be more widely used in everyday clinical case as well as in surgical research. PMID- 2577531 TI - [Methods and instruments for measuring and evaluating quality of life]. AB - The measurement of quality of life is a new and methodologically difficult approach for assessing the outcome of an operation. It is not a degenerated slogan of a superficial "recreation society". It must be determined by a team of surgeons and professionals using psychometry and social sciences. If possible, only validated test procedures should be employed in clinical trials. The quick development of new procedures should be avoided. The quality of life is today generally a more sensitive criterion for the success of an operation than perioperative mortality. PMID- 2577532 TI - [Quality of life--criterion in the treatment strategy of severely injured patients]. AB - A cohort study of 202 patients showed that all different aspects of quality of life--physical function, psychological function, social function and symptoms- were altered after multiple injury. Sixty-three percent of the patients rated their quality of life after trauma as average or bad. Since the quality of life is a relevant problem after trauma, it is necessary to use it as an important endpoint to judge results after multiple injury. Findings from such studies must be integrated into existing diagnostic and therapeutic concepts. PMID- 2577533 TI - [Quality of life as a justification for high risk therapeutic concepts--pouch or simple reconstruction]. AB - The classic endpoints of mortality and morbidity are no longer sufficient to evaluate new therapeutic concepts. Since significant differences are rarely found between the different patient groups, e.g. pouch vs simple reconstructions in the intestinal tract. Patients undergoing total gastrectomy have a better quality of life after receiving a Hunt-Lawrence-Rodino-pouch than after simple esophagojejunostomy. Similarly ileoanal pouch reconstruction in the pelvis after total colectomy impairs a patient's well-being less than classic enterostomas. Colonic pouch after following very low anterior resections could provide a new approach by substituting for rectum capacity. PMID- 2577534 TI - [Quality of life from the viewpoint of a general practitioner]. AB - Permanent loss of physical or mental abilities in the course of disease or trauma changes a person's lifestyle, causes uncertainty and cancels general standards. The patient feels a diminishment of his quality of life and becomes aware of being a living creature. He must not despair. He needs help to come to terms with his illness. What has he lost? What has remained? What are his new possibilities? In his search for a new concept of life he should not be left alone. This is a task for a good doctor. PMID- 2577535 TI - [Continued education at a university clinic with integrated specialties]. AB - During a 14 year period 145 medial doctors were employed at the Chirurgische Universitatsklinik Koln 45 became certified general surgeons after a mean of 7.2 years. 18 received a PhD. 4800 operations year permitted the training and qualification of 0.7 doctors for the subspeciality vascular surgery and 0.8 doctors for traumatology per year. Despite extended selection 53 did not accomplish board certification for surgery in the hospital of their initial training. PMID- 2577536 TI - [Continuing education in a department system (Hannover Medical School)]. AB - Among 100 surgical trainees (1/89; chief residents: n = 24) 34 finished their program (median age: 34.5 Y) after a mean of 6.3 years. During the program the trainees rotated in at least three different clinics and performed the required number of operations. Since 50% of the trainees are in the first 3 years of training 63.8% of all operations are currently performed by chief residents. This allows only three operations/month/trainee. Until 1988 the concept of qualified surgical training in a department was ensured. Due to an increase in trainees (+36%) the training will be prolonged in the near future. PMID- 2577537 TI - [Continued education from the viewpoint of the young surgeon]. AB - Acquired operation skills suffer due to the gap filling gathering of surgical experiences in the operating room. The up to date passing on of information to surgical housemen can be improved by replacing it in part by training programs. The proposed dynamic program of an operation syllabus helps to achieve a better surgical education of housemen. Research programs should be installed as a part of surgical training. Due to the extend of their surgical duties and extra lectures housemen need a new syllabus regulation that meets the requirements stated above. PMID- 2577538 TI - [Contents and curriculum in continued education for surgeons]. AB - The need for continuing medical education results from the challenge of retaining competence in treating patients. The quality of care is thus directly related to continuing medical education. Contents are knowledge as well as behaviour. Methods should be orientated towards personal needs and problems encountered. Selective and critical reading is of paramount importance. Of equal impact are more or less formalized personal interactions. Learning by teaching is an effective means of continuing medical education. PMID- 2577540 TI - [The academy for surgical postgraduate education and practical continued education of the Professional Society of German Surgeons]. AB - The aim of the academy is to present an up-to-date knowledge of all fields of surgery to young surgeons in the 5th/6th year of education. The main topics are taken from general, trauma, vascular, pediatric, neuro- and heart-surgery. The meetings are held once per year in five different cities in Germany. The second branch of the academy is an annual symposium dealing with five different current events that will be discussed each for half a day. Furthermore there is offered a course for ultrasound and another for endoscopy. PMID- 2577539 TI - [Legal requirements for continuing education and legal control]. AB - The patient has a claim to treatment commensurate with the standard of an experienced specialist. He who performs a service in which he is incompetent or no longer competent increases the risk of the treatment and at the same time exposes himself to the accusation of criminal responsibility. The systematic provision of continued education and advance training is essential to guarantee professional qualifications. This also includes the requisite organization (procedural quality) and the provision of appropriate personnel, equipment and premises (structural quality) at the place of surgery. PMID- 2577541 TI - [Morphologic aspects of the infected pleural effusion]. AB - Acute empyema is characterized by purulent effusions. Fibrinous adhesions may form between the pleural surfaces. If the purulent exudate is insufficiently resorbed, pronounced organisation and demarcation of the exudate occurs in the intermediate stage. This leads to scar formation or to completely demarcated empyema remnants in late stages. Besides its classic causes traumatic and iatrogenic injuries are increasingly causing empyema. Differential diagnosis must include empyema-like effusions in cancer patients. The course of the disease depends on the virulency and the type of infection, as well as on the immunological state of the patient and the therapeutic regimen. PMID- 2577542 TI - [The pathogen spectrum in acute and chronic pleural empyema]. AB - A retrospective analysis of the causative organisms was performed in 162 cases of empyema: 132/162 (= 81.5%) cases had positive cultures. Twenty-two different organisms were cultured from 235 isolates. The aerobic gram-positive bacteria were the largest group (61.7%), followed by aerobic gram-negative rods (21.7%), anaerobic bacteria (8.5%), and mycobacteria (5.1%). 1.8 bacterial species were recovered for each case of empyema. Polymicrobial empyema accounted for 48% of the cases. Therefore more than one antimicrobial agent should be administered to ensure adequate coverage. PMID- 2577543 TI - [Dangers and errors in pleural puncture and placing suction drainage]. AB - Mistakes during puncture and drainage of the pleural space can result in serious complications. A few case reports are presented. Injuries of intrathoracic and intraabdominal organs can occur-, the latter mainly due to underestimating the elevated level of the diaphragm. Trauma of the liver and spleen are mainly observed in such cases. To avoid such life-threatening complications "blind" puncture and drainage should be avoided and visual aids such as fluoroscopy, CT and ultrasonography should be used more frequently. PMID- 2577544 TI - [Early and late pleural decortication--indications and technique]. AB - Our experience with 224 decortications performed between 1957 and 1987 is reported. Insufficient drainage of tuberculous and unspecific pleural empyema was the main indication. Haemothorax, pleural loculation and chronic serofibrinous pleuritis were indications of secondary importance. Mortality following decortication was on the order of 0.1% and postoperative morbidity, 3%. However, in the past 10 years there has been a general reduction of aggressive surgical treatment. Whereas decortication and thoracoplasty account for 12% and 4% respectively of our surgical pulmonary procedures, therapy with closed-tube drainage has increased to 84%. PMID- 2577545 TI - [Functional aspects of pleural empyema and pleural induration]. AB - Decortication for pleural empyema with or without residual cavities was performed in 161 patients. Indications were sanitation of infection sites and improvement of respiratory function. A total of 73.3% of the patients had a non-specific and 22.4% a tuberculous empyema. Postoperative complications included 8.7% wound infections and 1.2% recurring empyema. Operative mortality was 0.6%. To estimate pulmonary function, the preoperative values of blood gas analysis and vital capacity were assessed in 75 patients and compared with those obtained after one year. A relatively slight improvement was seen only in those patients who had a preoperative reduction of vital capacity amounting to more than 40%. An indication for decortication solely to improve pulmonary function is rare. As a rule decortication is indicated for the simultaneous removal of septic foci and functional improvement. PMID- 2577546 TI - [Therapy of parenchyma and bronchus fistula in chronic pleural empyema and the remaining empyema cavity]. AB - The peripheral bronchial fistula, which is not visible by direct endoscopic examination, is closed by endoscopic application of fibrin glue. Sometimes only conservative therapy with irrigation of the pleural space is sufficient and effective. The postlobectomy fistula of the bronchus stump is treated by preoperative puncture and irrigation of the pleural space, followed by a corrective reamputation of the stump of the bronchus or a sleeve resection with end-to-end anastomosis. The post-pneumonectomy fistula has to be corrected by preoperative irrigation of the pleural space and a corrective second amputation by an extrapleural transmediastinal procedure. Sometimes it is necessary to use an opposite posterior access. An alternative is to cover the stump by an intercostal muscle flap without directly closing the fistula by suture. The remaining pleural space must be obliterated by using an additive pedunculated muscle flap of the thoracic wall. PMID- 2577547 TI - [Pleural empyema in childhood]. AB - Empyema is a rare parapneumonic complication in children. The use of antibiotics and closed-tube thoracostomy drainage has superseded operative procedures like decortication even in anaerobic infections. Only a few authors still recommend early decortication. However empyemas based on malformations such as lobar emphysema or cystic lung should be treated surgically. PMID- 2577548 TI - [Results and complications of treatment of acute and chronic pleural empyema--a retrospective analysis of the last 5 years]. AB - In 162 patients treated surgically for pleural empyema, 212 surgical interventions were necessary. As primary treatment cest-tube drainage was more effective than closed chest tubes. Decortication, which was carried out in 43 patients, was followed by further surgical procedures in three patients. If primary treatment is not effective early decortication is indicated to avoid septic complications (30-day mortality amounted to 7.4%). Two patients died from septic complications. PMID- 2577549 TI - [Pleural empyema as a complication of gastrointestinal interventions]. AB - The diagnosis of empyema following gastrointestinal operations is usually established at an early stage (Stage I/II in 23 of our own 29 patients). The decisive factor in therapy is the careful and precise insertion of a drainage tube under radiologic control (ultrasound, CT) followed by efficient suction drainage. Nevertheless mortality in this special group of postoperative septic complications was 56%, since extrathoracic sepsis could not always be eliminated promptly enough when diffuse peritonitis was the source of sepsis. PMID- 2577550 TI - [Pathophysiologic principles of modern liver surgery]. AB - Successful liver surgery depends on the regeneration of the liver. Most of our knowledge about regeneration stems from experimental studies in rats. While morphological regeneration occurs early more sophisticated functions such as bile salt production and bile salt conjugation takes a long time to normalize. A review is given of the many factors that contribute to regeneration. The object of most current interest is the role of fibronectin. After experimental hepatectomy the secretion of plasma fibronectin increases. This might be the single most important factor involved in hepatic regeneration. PMID- 2577551 TI - [Liver surgery in the repertoire of the general surgeon]. AB - In 1987, 2082 operations of the liver were performed in Germany by 196 of 230 consulted surgical departments in general hospitals. Surgery for liver injuries predominates in suburban hospitals, where as planned interventions are more often performed in main clinics. Our hospital resections of 1-6 subsegments of the liver in 134 patients averaged a mortality of 4.5%. Problems of benign and malignant tumours as well as of the chronic inflammed Echinococcus cyst are mentioned. The standards of the apparative assistance is interpreted and procedures are explained. PMID- 2577552 TI - [The European liver surgery topic--recent developments in liver surgery (in situ protection and ex situ operation)]. AB - Ex situ operations on the liver, a new surgical approach, and operations on a vascularly isolated and in situ hypothermic-perfused liver were performed in 12 patients. The indications for either approach were limited to patients for whom a conventional approach was impossible or seemed insufficiently radical. In one case a huge symptomatic focal nodular hyperplasia in segment IV became resectable only with the ex situ-technique. Our first experience showed that preoperative cholestasis is a high-risk factor for postoperative hepatic insufficiency; three patients with marked preoperative cholestasis died. In patients with good preoperative liver function these two approaches allow a more radical liver resection and are the only possibility for tumor resection in particular situations. PMID- 2577553 TI - [Surgery of liver metastasis]. AB - Technical improvements in liver resection therapy have forced optimism towards an extended indication for treatment. Operative mortality has improved, and a median survival time of 30 months, and 5 year survival rates of about 30% are reported. Perioperative course of CEA, time of onset of liver metastases, intrahepatic distribution and extrahepatic disease are factors of prognostic relevance. However, the intensity of follow-up, statistical artefacts and the time period reported on, severely influence survival curves. Additional therapeutic efforts are necessary to improve the number of patients that may benefit from surgical therapy of colorectal liver metastases. PMID- 2577554 TI - [Combined oncologic methods in primary tumors and metastases of the liver]. AB - In the past ten years 74 patients with carcinomas of the liver and 575 patients with liver metastases have been treated at the surgical clinic in Giessen. The median survival time of patients suffering from primary liver cancer was 364 days with combined treatment, but only 123 days with monotherapy. Similar results were obtained in patients with metastases (median survival time 365 days after combined therapy, 216 days after monotherapy). The results of this retrospective study suggest that a combined therapy is superior to single treatment regimen. PMID- 2577555 TI - [European topic: liver surgery II--regional chemotherapy]. AB - The most important methods of regional chemotherapy are exemplified by 657 cases of primary and secondary liver only malignancies. I. Adjuvant portal therapy of the liver with resection of the colorectal primary malignancy seems to be advantageous for advanced tumors. II. It is still unresolved whether survival is prolonged by adjuvant treatment of the liver following curative resection of colorectal liver metastases. III. The median survival time (FUDR, pump) is 17 months for palliative local chemotherapy of unresectable colorectal liver metastases. IV. Primary non-resectable liver malignancies show the best results after chemoembolisation (Frankfurt method). PMID- 2577556 TI - [The procedure in recurrent tumors of the liver]. AB - From 1981 to 1988, 13 patients with liver metastasis and 7 patients with primary hepatic tumors underwent a second hepatic resection for tumor recurrence. A second resection was feasible even after an extensive first resection. Several patients experienced tumor recurrence shortly after the first resection, but lived a long time after the second resection. The actuarial survival after a second resection for colorectal metastasis was similar to that after the first resection. Therefore a second resection for tumor recurrence is reasonable and may prove especially important in individual situations. PMID- 2577557 TI - [Liver transplantation in tumors]. AB - According to the European Liver Transplant Registry the percentage of patients selected to receive liver grafts for malignant liver disease decreased from 40% in 1983 to 23% currently. This development is due to disappointing results: 2 year survival rates of about 25-30% have been reported for malignant diseases compared to about 70% for benign diseases. Correlating the stage of the primary tumor and the survival time according to TNM-grading recent publications now show that the T1-3 and N-0 stage are clearly prognostic for long-term survival in contrast to a T-4 or N-1 stage which indicate a limited prognosis for about 90% of patients with HCC and Klatskin carcinoma during the first postoperative year. PMID- 2577558 TI - [Surgery of benign liver tumors]. AB - The most frequent benign liver tumors are hemangioma, focal nodular hyperplasia (FNH) and adenoma. It is essential for the diagnosis to differentiate these lesions from malignant tumors. While sonography, bolus-CT scan, chole-/bloodpool scintigraphy usually yield a safe diagnosis of hemangioma or FNH, adenomas do not show characteristic features. Operation is indicated for hemangioma of FNH only in case of tumor growth and/or symptoms. Operation for adenoma is as a rule indicated because of possible malignant transformation or uncertain differentiation from malignoma. Operative procedures include anatomical/atypical liver resection, ex situ resection or liver transplantation. PMID- 2577559 TI - [Shunt surgery with reference to indications for liver transplantation]. AB - Sclerotherapy and protosystemic shunt surgery are established procedures for treating bleeding esophageal varices. Liver transplantation (OLT) has not yet been established as primary therapy of portal hypertension. In a series of 43 patients with uncontrollable bleeding, shunt surgery was employed in 26 patients with contra-indications to OLT and in 2 whose liver disease had not progressed. In the remaining 15 patients, OLT was performed in urgent (n = 8) and emergency settings (n = 7). The results obtained indicate that immediate shunting in nontransplant candidates results in one-year survival for 67-83% of Child's class A or B Patients and only 42% Child's C category regardless of the type of shunt procedure performed. In transplant candidates with a similar risk status (Child's B and C) 5 of 8 patients receiving an urgent transplant and 4 of 7 patients receiving emergency OLT during active bleeding survived for one year or more. These results indicate that bleeding varices can be treated successfully by OLT. PMID- 2577560 TI - [Medical aspects of the artificial liver]. AB - Artificial liver support may be indicated in cases of fulminant toxic or drug induced liver failure, in fulminant viral hepatitis, after surgical procedures such as extended liver resections or liver transplantation with primary graft failure, and in some cases of chronic endstage liver disease. Neither artificial nor biological liver support systems have shown any convincing results, whereas plasma exchange combined with intensive medication is suitable for temporary liver failure or for providing support until a donor organ for liver transplantation becomes available. PMID- 2577561 TI - [Laser qualities and areas of application, current status and perspectives]. AB - Laser beams are used in a variety of surgical applications and promise to become even more meaning in the next years with the advent of new technology. Depending on the energy density, application time and wavelength of the laser beam, a variety of interactions takes place with tissue. Some of these are now standard procedures for cutting, welding and coagulating. Other interaction are being used experimentally in therapeutic and diagnostic procedures, e.g. stone destruction and angioplasty. Laser induced fluorescence and holography have opened a wide range of spectroscopic analysis. Raman-spectroscopy will allow respiratory gas analysis in a split second. Photoablation holds great promise for athermic cutting, angioplasty and the spectroscopic differentiation of tissue. PMID- 2577562 TI - [Laser surgery of parenchymatous organs]. AB - Several physical methods of cutting and/or coagulating are available in addition to CO2 or Nd:-YAG-lasertechnology for surgery of the parenchymal organs. The promising experimental results obtained in partial hepatectomies were not reduplicated in clinical situations. Exceptions are the contact Nd-YAG laser which had good or excellent results and the use of lasers in pediatric surgery of parenchymal organs, depending on the patient's physiological condition. If the corresponding technological requirement are realized, new applications of lasers will emerge, above all those using sonographic or endoscopic techniques. PMID- 2577563 TI - [Endoscopic use of the neodymium YAG laser in the upper and lower gastrointestinal tract]. AB - Endoscopic neodymium-YAG laser therapy for the gastrointestinal tract has been proved since 1975. Mortality and time of convalescence of patients treated with laser for acute or potential bleeding lesions have been markedly reduced in contrast to surgery. Sessile neoplastic polyps can be removed endoscopically by laser. Laser recanalization of obstructed carcinoma or scars in the upper and lower gastrointestinal tract to relieve dysphagia or ileus improves the patient's quality of life and has benefits for subsequent operations. PMID- 2577565 TI - [Types of equipment, technical developments and peculiarities of extracorporeal lithotripsy--problems in locating the calculus]. AB - Three methods are used for the extracorporeal distintegration of gallstones and kidney stones. Shock waves can be generated by an underwater spark, the discharge of piezoelectric crystals, or electromagnetic waves. The shock waves must then be focussed to disintegrate the stones. Depending on how they are generated the focus of the shock waves is like a dot or an ellipsoid. In most cases the stones can be localized by ultrasound. X-ray localization should also be possible. PMID- 2577566 TI - [Does the lithotripter change gallstone surgery?]. AB - Extracorporeal shock-wave lithotripsy (ESWL) is a new method for treating gallstones. ESWL is an alternative method to cholecystectomy for treating symptomatic gallbladder stones--complicated cases excluded--in about 15% of all cases. The risk of stone recurrence with all its consequences (symptoms, complications, late mortality) has to be weighed against the higher morbidity and mortality of surgical treatment. ESWL can be used for bile duct stones instead of endoscopy. Concrements cannot be removed mechanically (10-20%) have been treated with a high success rate (80%) using ESWL. In summary, at present ESWL is restricted to a small number of selected cases. PMID- 2577564 TI - [Current state and perspectives of laser use in vascular surgery]. AB - We report on a project to determine the feasibility of treating carotid artery stenosis with the argon laser (1985) and the clinical results of recanalising peripheral arteries. Training for the above-mentioned project showed that sapphire-tipped Nd:YAG laser optical fibers are the proper instruments for recanalisation. New attempts with new catheter material should make the recanalisation of the carotid artery possible in the future. PMID- 2577567 TI - [New technical and methodologic developments in surgery: mechanical suture technique]. AB - Mechanical suture is possible by linear, circular and so-called anastomotic devices. Linear staplers work with metal clips and polyglactin, while circular stapler-anastomoses function with metal clips and the Murphy principle. Compared to hand suturing staplers have not only the advantage of saving time but they also provide for a simple closure of the duodenal stump, the bronchus and the safe anastomosis of the rectum and the esophagus. The clipless compression anastomosis seems to have a promising future. Its advantages include the absence of a foreign body, larger diameter of the anastomosis and no risk of postoperative haemorrhage. Our results with staplers (1987-1988) prove their superiority: there were only three insufficiencies among 140 circular anastomoses of the esophagus and the rectum. No complications occurred in 153 applications of linear staplers on the bowel and the lung. PMID- 2577568 TI - [Technical prerequisites for performing controlled studies with the goal: postoperative quality of life after gastrectomy]. AB - A study of 78 cases of gastrectomy in which two reconstruction procedures Roux-en Y + pouch and interposition + pouch were compared and which is still in progress, yielded the following results: 1. It is possible to use both methods only with staplers and have few complications in a time-saving procedure. 2. A Roux-en-Y + pouch takes mean = 50 min; an interposition + pouch requires mean = 90 min (net time of reconstruction). 3. It is sometimes impossible for anatomical reasons to use an interposition + pouch. 4. The more complex procedure--the interposition + pouch--does not have a higher rate of complications. 5. Technical development permits controlled studies investigating the long-term target: quality of life. PMID- 2577569 TI - [Tricks, errors and dangers in use of staplers in the upper gastrointestinal tract]. AB - Special technical procedures are the prerequisite for the successful use of stapling techniques in surgery of the upper GI tract. Organ surfaces which are to be connected by staplers have to be cleaned meticulously of all fat and mesenterium. Purse string sutures in the hiatus oesophagei should be done by hand. The instrument has to be inserted carefully to avoid leasons of the mesenterium. Kinking of bowel segments has to be avoided; the bowel or gastric segments must be spread over the circular staplers. Anastomoses should be checked for bleeding and patency. Thus stapling can be done successfully in routine resections of the stomach and in the transabdominal approach to cardia region and lower esophagus. PMID- 2577571 TI - [Tricks, errors and dangers in use of staplers in the colorectal area]. AB - Ten years' experience of performing 970 operations in which circular colorectal anastomoses were stapled chiefly in the lower two-thirds of the rectum according to the open standard method is reviewed. The deeper the anastomosis and the narrower the pelvis, the higher the rate of complications, especially leakages. This is not only due to pathological, anatomical reasons or technical difficulties, but also to inappropriate application and handling of the staplers. Accurate diagnosis and a systematic procedure after sufficient training can reduce this rate. A precise analysis of the mistakes and risks resulted in a number of standard techniques and tricks which perfect the use of this technology. PMID- 2577570 TI - [Stapler-dependent surgical procedures in the colorectal area]. AB - Since its introduction, stapling has gained considerable interest in colon surgery. The double stapling technique is a further development. From 1984 to 1989, 110 low anterior resections were performed at the Department of General Surgery, University of Goettingen. In 73 patients anastomosis was performed by double stapling; in 37 cases the EEA stapler was used. The double stapling group had an insufficiency rate of 2.7% compared with 5.4% in the EEA group. Another useful indication for stapler techniques is a reconstructive operation according to the Hartmann procedure. In none of 43 such interventions between 1983 and 1988 was insufficiency of the anastomosis seen. Another useful employment of staplers is construction of colonic reservoirs after proctocolectomy. PMID- 2577572 TI - [Technical aids by staplers in lung surgery]. AB - Linear stapling devices ensure a safe resection in lung surgery. They are not only convenient for closing the bronchial stump, but also highly efficient for dividing the main pulmonary artery or lobar veins. The superiority of stapling is immediately obvious in the division of fissures and tangential resections of lung parenchyma. Bronchopleural fistulas can be easily avoided. The safe and appropriate use of stapling divices makes a standardized procedure in lung surgery possible. PMID- 2577573 TI - [Errors and dangers in use of the surgical stapler in lung surgery]. AB - The staple closure of the bronchus, like the manual technique, depends on some essential prerequisites: vascular supply, the length and thickness of the bronchial stump, the resection line, the type of stapler and the size of staples used. GIA 55 or 90 instruments allow safe and simple closure of lung parenchyma. Familiarity with the stapling technique is essential for success. PMID- 2577574 TI - [Anatomy of the knee joint and its clinical relevance]. AB - The stability of the knee joint is ensured by dynamic and static structures. The most important medial structures are the medial collateral ligament, medial capsular ligament, posterior oblique ligament, semimembranous muscle, and the pes anserinus group. The main supportive structures on the lateral side include the iliotibial band, lateral collateral ligament, lateral capsular ligament, popliteal tendon, arcuate ligament, and the biceps muscle. The cruciate ligament pillar is the center of rotation. The classification of knee instability requires new orientation that places the main emphasis on the translation of the joint compartments and the description of the injured structures. PMID- 2577575 TI - [Diagnosis of fresh combined injuries of the knee ligaments (clinical and technical diagnosis)]. AB - Detailed information about the cause of the accident, possible previous injuries and a meticulous clinical examination are essential for a correct diagnosis. The Lachman test has been demonstrated to detect an ACL injury. Its reliability however is dependent on avoiding an inappropriate internal rotation and may be curtailed by voluminous musculature and a bucket-handle tear. Reproducible testing of the pivot shift can be carried out only under anaesthesia. Magnetic resonance imaging (MRI) is of high diagnostic validity in acute ACL injuries. With the aid of arthroscopy even partial tears of the ACL, chondral lesions and injuries of the dorsal parts of the joint are detected. Sometimes prior to an arthrotomy diagnostic and therapeutic arthroscopy are combined. PMID- 2577576 TI - [Treatment of fresh, combined injuries of the knee ligaments: conservative treatment]. PMID- 2577577 TI - [Open knee joint injuries (including vascular and nerve lesions)]. AB - Immediate definitive reconstruction of all damaged structures leads to better results than delayed operations. If direct closure of the joint is not possible, local rotational flaps, muscle flaps or free skin-fat tissue flaps (i.e. a scapular flap) may be used. In injuries of the popliteal artery, the interposition of a saphenic vein graft is preferable to local reconstruction of the artery. Nerve injuries are the only exception to comprehensive primary repair. Reconstruction in these lesions is usually done later when all wounds are healed. The postoperative treatment includes the use of continuous passive motion whenever possible. PMID- 2577578 TI - [Quality of life and general surgery]. AB - Currently the concept of quality of life is being discovered, analyzed and adequately defined for the field of surgery. The objective finding is being supplemented by a higher measure of subjective assessment. The aim is to intensify the individual side of the dialogue in order to achieve an approximately symmetrical partnership. As in the 19th century the faculty of medicine, including surgery, still understands itself as psychosomatic medicine; at the same time it has competency in the natural and humanistic sciences. The concept of quality of life adds useful and above all comparable parameters. PMID- 2577579 TI - [Early complications, concomitant and follow-up treatment of fresh combined knee ligament injuries]. AB - A graduated, concomitant and follow-up treatment of fresh knee-joint ligament injuries helps to reduce pain, restore mobility and increase muscular strength. By slowly increasing joint mobility, secondary ligament slackening is avoided. Likewise static loading should be increased gradually. Physiotherapeutic exercise techniques to restore proprioceptive ligamentous control mechanisms as well as transcutaneous electrical neurohpysiological stimulation, ice treatment, ultrasound and isokinetic training techniques support these measures. Early complications include infection and stagnating mobility despite intensive exercise treatment. Both require consistent, purposeful action. PMID- 2577580 TI - [External fixators in treatment of severe fractures of the pelvis]. AB - The use of external fixation for pelvic injuries is mainly determined by the type of pelvic girdle fracture and by the severity of the general injury. Exact diagnosis of the extent of injuries can be made with a pelvic X-ray a.p. Pennal's technique and CT imaging. The iliosacral joint can be repositioned by transduced compression via Schanzscrews inserted above the acetabulmum and directed toward the iliosacral joints. Triangular compression frame construction is applied along the plane of the pelvic inlet. The advantages include easier intensive care, early functional mobilization, minimised trauma and decreased blood loss. Disadvantages are the risk of pin tract infection and patient discomfort. Of 92 patients treated thus, these were 11 cases of ankylosis of the iliosacral joint, two malunions and two persistent instabilities of the pelvic girdle. PMID- 2577581 TI - [Change in external fixator and when in multiple trauma patients]. AB - External fixation of fractures in polytraumatized patients normally should be regarded as temporary. After the patient's general condition is stabilized, in most cases it is necessary to change the procedure in order to provide sufficient mobility of joints, timely bony healing and early mobilisation. The earlier the transition toward internal osteosynthesis, the lower the complication rate. The follow up of 37 polytraumatized patients who were subjected to 50 changes of method after primary external fixation is described. PMID- 2577582 TI - [Functional adjustment of joints with different mechanical stress]. AB - The density of osseous tissue and the alignment of the cancellous trabeculae of the hip joint depend on magnitude, direction and position of the resultant force affecting the hip joint. The cancellous architecture surrounding the acetabulum moreover is influenced by forces acting at the symphysis and the iliosacral joints. The articular bones of the ankle joint are subjected to compressive stress. In the lateral areas of the joint a bending stress which results from tensile forces exerted by the collateral ligaments is superimposed on the compressive stress. PMID- 2577584 TI - [Functional treatment of joint fractures]. AB - The absence of functional load causes damage to different extents in various structures of the joint. Especially cartilage, joint capsule and ligaments are affected. Although operative functional treatment provides better prerequisites for avoiding such damage compared to conservative procedures, the results are not satisfactory in nearly 25% of the cases. Functional treatment of fractures of the joint by extension and continuous passive motion are suitable wherever operative reconstructions do not seem successful or have been proven to be superior as in fractures of the calcaneus. PMID- 2577583 TI - [Current state of functional therapy. Definition and indications]. AB - Functional treatment can be defined as a form of therapy in which the involved segment of the locomotor system is either not immobilized at all or the immobilization is incomplete and lasts only for a limited time. Function of the involved segment is therefore restored during the treatment. Many fractures, especially those of the upper extremity, stable fractures as well as a number of joint injuries such as AC-joint dislocation, ankle ligament rupture and Achilles tendon rupture can be treated functionally. Functional Treatment is an integral part of regular conservative fracture treatment and also important for the operative management of fractures and joint injuries. PMID- 2577586 TI - [General principles and techniques of osteosynthesis in pathologic fractures]. AB - Skeletal metastasis and pathologic fractures are signs of progressing neoplastic disease, but they are not life-threatening events. Stabilization is necessary to diminish pain and to maintain mobility. Principles of surgical stabilization include rigidity for long-term functional use, nondependence on bone healing and salvage of as much bone as possible to maintain muscle attachment for limb function. This is achieved by integrating bone, polymethylmetacrylate and implant into a solid unit. In the treatment of pathologic fractures not caused by malignancy biologic factors such as bone transplantation play a predominant role. In case of infection stability and vascularity of the bone is of utmost importance. Vascularity is achieved by pediculed or free-tissue transfer. PMID- 2577585 TI - [Pathologic bone fractures: definition and classification]. AB - A bone fracture is a complete or incomplete discontinuity of bone caused by a direct or indirect force. A pathological bone fracture is a bone fracture which occurs without adequate trauma and is caused by a preexistent pathological bone lesion. Causes include resorption of bone mass (osteoporosis), reduction of bone quality (osteomalacia, osteonecrosis), insufficient bone production (osteogenesis imperfecta, fibrous dysplasia), augmented bone resorption (giant cell granulomas, aneurysmal bone cyst), pathological bone remodelling (Paget's disease), or local bone destruction due to tumorous growths. A pathological bone fracture has to be detected clinically as well as radiologically and its cause diagnosed histologically in order to ensure adequate therapy. PMID- 2577587 TI - [Quality of life after trauma surgery interventions]. AB - Integral factors of a patient's Quality of life include the absence of pain, unimpaired mobility, intact capacity to think and judge, as well as access to a good social environment. Surgery for injuries provides a prime example of how much surgery can influence the quality of life. The abrupt change from psychosomatic integrity to a more or less reduced quality of life, especially in trauma patients, is particularly upsetting to the patient. Thus all possibilities of effecting a rapid change together with improvement by operative measures are especially important. Injured patients expect an operation to give quick and, if at all possible, complete reinstatement of the their condition before the injury. The great progress that has been made in surgery, especially in accident surgery, however, should not delude us that there are still technical and biological limits to full recovery. PMID- 2577588 TI - [Osteoporosis as a cause of pathologic fracture]. AB - Estrogen deficiency causes loss of trabecular bone, leading to fractures of the spine. One-third of all postmenopausal females suffers from type I osteoporosis, which is characterized by chronic pain, hump and height reduction. Fluorides, calcium plus vitamin D3 are effectively treat of the disease if given over 3-4 years. Calcitonin blocks pain episodes in more than 50% of the patients. Calcium deficiency and reduced mobility together with unknown reasons cause type II osteoporosis, which also affects males. Fifty thousand hip fractures occur annually in the Federal Republic of Germany and require additional surgical therapy. PMID- 2577589 TI - [Benign and semi-malignant bone tumor and tumorous lesions as a cause of pathologic fracture]. AB - The aim of the treatment in cases of impending or manifest fracture within the area of a benign of semimalignant bone neoplasm is total osseous healing with a complete as possible preservation of function. In case of benign tumors and tumorlike alterations satisfactory results are often achieved by thorough curettage, perforation of sclerotic ridges and extensive cancellous tissue grafts. Relapses are often due to inadequate operative techniques. Semimalignant osteoclastomas require frozen section. Even in cases of disadvantageous localisations (neck of the femur, proximity to acetabulum, proximity to wrist), meticulously executed electrocauterisation allows a more radical operation and the maintenance of function of the joint. PMID- 2577590 TI - [Bone infection as a cause of pathologic fracture]. AB - A long persisting chronic recurring ostitis disturbs above all the differentiated conversion of fibrous bone into strong lamellar bone. The more that other factors disturb the vitality and vascularity of the bone, the more dystrophy, sclerosis and so-called crenae develop. Together this leads to new pathological refractures during inflammatory bone processes. To avert these dangers adequate infection prophylaxis and therapy are necessary as well as consistent observance of biomechanical and biological principles. PMID- 2577591 TI - [Malignant tumor (including metastasis) as a cause of pathologic fracture]. AB - Pathological fractures due to primary malignant bone tumors are extremely rare. The first step in their treatment is biopsy and stabilization with external or internal fixation including bone cement. The tumor is then typed, graded and staged. A multimodal therapy follows. In cases of bone metastases the tumor is immediately removed and internal fixation or endoprostheses are used for stabilization. Operative procedures and results are demonstrated in patients with metastases of the proximal femur. PMID- 2577592 TI - [Endoscopy and sonography change a specialty: exemplified by gynecology]. AB - Pelviscopy, a surgical technique employing new apparatuses and instruments, has replaced the classic laparotomy in gynecology in over 75% of cases. According to an organ-oriented surgical catalogue, pelviscopic surgery has proven to be successful in the treatment of ectopic pregnancy (nearly 100%), ovarian cyst enucleation, oophorectomy, and myoma enucleation. In cases of extensive bowel and omental adhesiolysis, pain-free status is achieved in 60%. Second-look and repelviscopy enhance the success rate of adhesiolysis. The results achieved in Kiel have been statistically proven in over 15,000 peliviscopies. PMID- 2577593 TI - [Gastrointestinal hemorrhage--change in therapy concepts by endoscopy]. AB - Since the introduction of endoscopy in diagnosis and treatment of gastrointestinal bleeding in the early seventies, emergency endoscopy has changed the therapeutic concept of this disease. At first the task of emergency endoscopy was limited to location of the bleeding site. In the eighties endoscopic hemostasis was established in many hospitals. In addition, preselection of patients who will benefit from surgery has become possible by endoscopic means. These factors have reduced significantly mortality due to GI bleeding. PMID- 2577594 TI - [Endoscopy in diseases of the bile ducts and pancreas]. AB - The results of endoscopic therapeutic methods (EST, TPCD), which changed the therapy of the frequent biliary duct and of the diseases of the pancreas, are discussed and the literature and treatment of our own patients are discussed. The choice of optimal therapy for the patient is possible only if endoscopic methods are part of a combined endoscopic-surgical concept of therapy selected in close cooperation with the surgeon. The therapy of cholelithiasis and acute pancreatitis are used as examples. PMID- 2577595 TI - [Quality of life after heart surgery interventions including transplantation]. AB - The results of cardiac surgery thus far have been objectified mainly by clinical and hemodynamic parameters. However, there is a striking discrepancy between the operative success and the quality of life, especially as regards the patient's return to work, which seemingly correlates with a multitude of socioeconomical and psychological factors. Increased attention therefore should be given to encouraging patients who have undergone heart surgery to resume as broad as possible a range of normal life activities. PMID- 2577596 TI - [Microscopic endoscopic tumor surgery. What is possible?]. AB - The technique of transanal endoscopic microsurgery was used to remove sessile polyps which involved the whole circumference and were up to 8 cm long. This defect is always closed endoscopically by transverse continuous suture; in case of segmental resection end-to-end anastomosis is performed. The complication and recurrence rate is lower than that of conventional procedures. Moreover the postoperative course is shorter and the patient is free of pain. A second example of minimal invasive surgery is the endoscopic-microsurgical dissection of the esophagus. Here the whole esophagus is exposed endoscopically using the newly developed operating mediastinoscope. The definite superiority of this new technique to conventional procedures was proven by a controlled randomized experimental animal study. PMID- 2577597 TI - [Ultrasound in surgery--value and dangers of a new development]. AB - The value of US in enlarging the spectrum of diagnostic examination has been recognized. This also true for surgery in elective as well as emergency and intraoperative situations. Problems with US may arise when used by surgeons who do not have time enough for qualified training in this field due to intensive operation schedules or in cases where a 24-h US service is unavailable. Intensive education in diagnostic US for surgeons can help to avert this problem. PMID- 2577598 TI - [Knee arthroscopy today]. AB - Arthroscopy is not only the most reliable diagnostic tool in disorders of the knee joint but it also allows a one-step procedure of diagnosis and therapy in many cases. Most arthroscopic operations can be performed without hospitalisation. Post-operative morbidity is usually low. An excellent or good result was achieved in 91% of arthroscopic partial meniscectomies. Costs were reduced by sFr 6000 to 7000 for arthroscopic operations compared with arthrotomy. The advantage of most arthroscopic procedures performed today has been proven; however, the clinical value of others (i.e. arthroscopic suture of meniscal tears, repair of cruciate ligaments and abrasion-arthroplasty) is still not clear. The frequency of complications is low (0.56%), and infections occur in less than 1%. PMID- 2577599 TI - [Effect of endoscopy on surgery of veins]. AB - Endoscopic techniques influence the diagnosis and management of surgical problems more and more. The endoscopic subfascial dissection (ESDP) of incompetent venous perforators, which are often found in conjunction with a venous stasis ulcer, is a prime example. The two principles of surgical management, the interruption of blood flow through the perforators and the performance of a medial paratibial fasciotomy, are fulfilled with this technique. The evaluation of this new operative extraluminal endoscopic procedure using specific criteria suggests that it will become increasingly wide-spread. PMID- 2577600 TI - [Quality of life after thoracic surgery]. AB - Quality of life is difficult to define. The Karnofsky-Index has little contributed to the objective evaluation and self assessment appears to be rather important. A study of 88 patients of which 58 were subjected to thoracic surgery revealed, that quality of life following thoracic surgery is basically dependent on the postoperative physical condition. Following surgery of the esophagus the ability to swallow, after lung resection the respiratory capacity are important for the postoperative well being. PMID- 2577601 TI - [Value of triad operation in multilevel occlusion]. AB - A triad procedure, i.e., aorto iliac inflow repair + profundaplasty + lumbar sympathectomy, offers a simple and effective approach for revascularisation in patients with multilevel arterial occlusive disease. Approximately 85% of the affected limbs at stage III-IV may return to a stage I or II. Only 10% require an additional distal bypass. Indications, technical aspects and late results are presented. PMID- 2577602 TI - [Bypass spanning the knee joint with synthetic prosthesis]. AB - Synthetic tubes are the second choice for below-knee bypass materials. The ring reinforced thin-walled Goretex-PTFE graft is an approved material which was tested in a multicenter study. The primary 3 years patency for below-knee femoral popliteal bypass was 64%, for crural bypass 39%. A total of 195 grafts have been implanted. Long-term patency depends very much on the run-off conditions (81% in good and 43% in bad cases). The over-all limb salvage rate was 80% after 3 years. PMID- 2577603 TI - [Revascularization of the isolated popliteal segment]. AB - An alternative to crural reconstruction of obliterations of the popliteal vascular axis and an angiographically ascertained isolated popliteal segment is a bypass to the isolated popliteal segment. A patency rate of 82.7% was found 1 year after bypass; after 3 years the patency totaled 76%, and after 4 years the cumulative patency rate amounted to 59%. A comparison of these results with those of crural reconstruction (a patency rate of no more than 60% after 3 years) proved the superiority of the bypass. PMID- 2577604 TI - [Femoro-crural bypass--orthotopic]. AB - From 1980 to 1988 248 femoro-distal bypass procedures were performed in anatomical position for limb salvage due to peripheral artery disease. Bypass material strongly influenced bypass patency rate. The analysis showed a highly significant difference between venous and prosthetic grafts over a period of 3 years (p less than 0.0001). Use of the composite jump craft technique increased patency rates after 3 years to 58%, which is close to that of vein bypasses (63%). Use of prosthetic bypass material alone achieved a patency rate of only 38%. It is concluded that technically more difficult procedures such as the composite jump graft technique are superior to prosthetic bypasses. PMID- 2577605 TI - [Extra-anatomic crural reconstruction]. AB - In the difficult field of crural surgery technical details are very important. However only if we succeed in demystifying the crural bypass and integrating it in to general surgery, will we succeed in drastically lowering the number of amputations. To achieve this aim PTFE graft was used as extraanatomic bypass. Based on experience with more than 500 operations (since 1. January 1980), the Linton patch, and not the AV-fistula, is the best additional measure for treating distal anastomosis. PMID- 2577606 TI - [Cost-benefit analysis of saving the leg]. AB - To acquire cost-benefit analysis data for limb salvage a prospective study was performed between 1. January 1988 und 30. Juni 1988, including 128 admissions for AOD Stage IV or acute complete ischemia. After dividing the patients into three groups--limb salvage (LS), limb loss (LL) and primary amputation (PA)--the average total costs per admission were calculated. In the LS group these costs amounted to DM 14,652 for all cases and DM 14,069 for the survivors, in the LS group to DM 25,364 and DM 27,583 and in the PA group to DM 22,946 and DM 28,186. Therefore in light of the total costs alone every effort should be made to salvage threatened limbs. PMID- 2577607 TI - [How much foot is better than none?]. AB - The long-term analysis of ten cases of borderline amputations at midfoot level permits the following conclusions. The functional result of borderline amputation ad midfoot level depends on several parameters, including the elevator effect of the muscle antagonists; the quality of the integument; the traction between full thickness skin and split-thickness skin grafts; local pressure over prominent bones; osteoarthropathy and osteolysis, especially in the diabetic foot; and subjective circumstances including general state of the health, age and activities. PMID- 2577608 TI - [Current state of amputation surgery]. AB - Upper extremities: Traumatic amputations should be re-planted whenever possible. Lower extremities: Traumatic amputations must never be replanted! Arterial occlusive diseases cause the majority of amputations (ref. to indication, technique, rehabilitation). Borderline amputations are considered only after arterial reconstruction (profundaplasty) or in diabetics. The major preferential amputation is the knee disarticulation, since it results in less trauma and promotes quick rehabilitation, especially in geriatric patients. PMID- 2577609 TI - [Determining the amputation level]. AB - The peripheral amputation level (at the knee or below the knee) is the most important factor in obtaining optimal functional results and reducing the relatively high operative mortality of above-knee amputations in patients with occlusive arterial disease. Measurement of transcutaneous oxygen tension has proved to be a helpful tool for realizing this therapeutic principle. Comparison with another group of amputees without pO2 measurement indicates that the ratio of above-knee to below-knee amputation or knee disarticulation could be changed from 2:1 to 1:4. The reduced number of above-knee amputations also resulted in decreased operative mortality (3.2% vs 11.4%). PMID- 2577610 TI - [Minor amputations in treatment of the diabetic foot]. AB - Major amputation is a radical therapeutic principle which should not be undertaken without angiographic evaluation. Since the goal of limb salvage is to limit the ischemic tissue lost in an acral area, it favours minor "borderline" amputation. Of 597 stage IV patients 362 underwent arterial reconstruction (40% diabetics). Limb salvage was performed in 75% of the patients. Followup after 6 years showed that 33% of the patients were able to walk, and 17% had had a secondary major amputation. PMID- 2577611 TI - [Lower leg amputation--vascular surgery aspects]. AB - Of 2,816 arterial reconstructions performed between 1984 and 1988 at the AK Hamburg, 341 amputations were necessary. Only 32 lower-leg amputations were possible. Although all facts indicate that the knee joint is best preserved, it is not always possible due to underlying arteriosclerosis. If a well-vasculated dorsal skin-patch can be formed, the operation is surgically unproblematic. PMID- 2577612 TI - [Knee exarticulation: technique for amputation of ischemic extremities]. AB - A knee disarticulation or a trough-knee amputation stump is superior to an above knee stump. Knee disarticulation does not require that bone be sectioned or muscle cut. The stump allows total end-load capacity. The muscle balance remains undisturbed. Due to the bulbous shape of the stump prosthetic fitting of modern appliances no longer presents problems. An operative technique especially developed for vascular patients is described in detail, including the postoperative treatment and the principles of prosthetic fitting. PMID- 2577613 TI - [When is primary amputation of the upper leg indicated?]. AB - Every patient suffering from arterial occlusive disease has to be considered a candidate for a bilateral amputation. Infragenual amputation is preferable if at all possible. Poor wound healing and reamputation at a higher level are factors to be expected in 20-30% of these patients. Therefore primary above-knee amputation is indicated only if a more distal amputation level is not possible, or if lower amputation offers no advantage to the patient. The question must be answered in each individual case. PMID- 2577615 TI - [Prosthetic management of amputees]. AB - The prosthesis of a lower limb amputee usually consists of a socket custom made out of wood, glass fiber, reinforced resin or other plastic material. This is also true for modern flexible sockets. Individually selected components depending on the amputee's level of activities, such as hip, knee and ankle joints, torsion adapter and different prosthetic feet, are produced by the orthopaedic industries. Function, however, depends significantly on the quality of the stump created by the surgeon. Even a skilled prosthetist cannot improve the stump. PMID- 2577614 TI - [Subtotal and total traumatic extremity amputation--when replantation, when amputation?]. AB - The major problems besetting replantation of a limb are the very limited tolerance of muscle tissue to ischemia (in our experiences 5 h) and the possibility of severe postischemic complications either in the limb itself (capillary thrombosis, muscle necrosis) or systemically (kidney failure, speticemia). Between 1975 and 1988, 66 limb replantations (57 arms, 9 legs) were carried out. All nine legs had to be reamputated. Forty-five of the 57 reattached upper extremities (80%) healed without any major complications, 60% exhibited good or very good results (Grade II or I, Classification by Chen). PMID- 2577616 TI - [Rehabilitation of amputees]. AB - An optimal rehabilitation result following amputation in each individual case depends on the smooth cooperation of the surgery department and the rehabilitation clinic. Equally important ist the good cooperation between physicians, physical therapists and orthopedic technicians. A decisive influence on the outcome of rehabilitation is already exercised with the choice of height of the amputation site and the operative technique. A positive development can be intensified by an early prosthesis fit and practice. It is imperative that the amputation be seen as the beginning of the patient's rehabilitation and not as a failure and the end of efforts to preserve the extremity. The degree of mobility achievable depends very decisively on the patient's remaining ability and will to succeed. PMID- 2577618 TI - [Deep rectal cancer: selection of surgical methods in relation to site and extension]. AB - The procedure of choice for most pT1 and a few pT2 tumors in the lower-third of the rectum is excision or local endoscopic polypectomy. In 602 radically resected low rectal carcinomas, the local recurrence rate for LAR was 18% and for APE 17%. There was no difference in local recurrence for UICC stage I and II tumors with a small (less than or equal to 2 cm) versus a large (greater than or equal to 3 cm) distal margin. However, in UICC stage III B and III C there was a statistically significant difference between a small (56%) and a large (22%) distal margin for LAR, while the local recurrence was 29% for APE. LAR in stage III B + C should be performed only when a distal margin of 3 cm is guaranteed. PMID- 2577617 TI - [Prognostic factors in rectal cancer]. AB - After surgical resection of rectal carcinoma the R (residual tumor) classification and pTNM are independent prognostic factors. In patients with residual tumor, presence or absence of distant metastases influences prognosis. The pTNM-defined stage and substage is of prognostic influence for patients without residual tumor. In a study of 597 patients multivariate analysis was used to identify additional prognostic factors for individual substages. Similar studies on larger patient material are needed for further clarification of these prognostic factors. PMID- 2577619 TI - [Principles, technique and results of short continence resection]. AB - Ultra-short resections of the rectum have been recommended for rectal carcinomas that extend less than 8 cm above the dentate line in order to preserve anal continence. Resection of the main lymphatic pathways together with the adjacent lamellae is important. Valves in the rectal lymph vessels allow lymph fluid to drain only cranially. There are no lymph nodes behind the dorsal adjacent lamella. We recommend a transano-abdominal approach. A five-year survival rate of 50% was found in 156 patients with rectal carcinomas who underwent rectal resections and colostomies, 62% in those receiving low anterior resections and 69% in those with ultra-short sphincter-preserving resections. PMID- 2577620 TI - [Anastomosis techniques in deep rectal resection]. AB - Low anterior resection is defined as a procedure restoring continuity when rectal cancer is located within 12 cm of the dentate line. Rates on anastomotic leakage are similar for stapled and sutured anastomoses. Critical for the success of either procedure are sufficient mobilisation of the left hemicolon to achieve tension-free anastomosis, precise lymphadenectomy according for these standards of surgical oncology and adequate vertical and horizontal dissection of tissue adjacent to the tumor. The local recurrence rate is determined by tumor stage an safety margin. PMID- 2577622 TI - Local recurrence after anterior resection. AB - Local recurrence after anterior resection is due to both pathological and surgical factors. The pathological factors include level of tumour, pathological stage, histological grade and the occurrence of perforation. Particularly important is the extent of local spread, which can be identified clinically by digital palpation and by endoluminal ultrasound. Extensive local spread identified preoperatively is related to local recurrence after surgical treatment. Surgical reports of the incidence of local recurrence from less than 5 30%. There is strong evidence of a surgeon-related variable. Mesorectal excision may be associated with a low rate of local recurrence. Pathological involvement of the lateral margin of excision is related to local recurrence. Implantation by viable tumour cells is likely to be related to anastomotic recurrence. PMID- 2577621 TI - [Functional results after continuity resection of the rectum]. AB - Disturbances of anal continence and bladder and sexual functions are frequently a consequence of low anterior resection. In a prospective study of 60 patients anal continence and bladder control were examined for objective results in function. Within the first 3 months after surgery 50% of the patients had a deficiency in anal continence due to reduced reservoir function. This was not evident in cases with good anastomosis healing in the second postoperative half-year. Especially male patients (46%) developed a dysfunction in micturition which required urologic treatment. PMID- 2577623 TI - [Deep rectal cancer: local excision--methods, results, complications, recurrences]. AB - Early rectal carcinoma of the lower rectum without involvement of the muscularis propria should be considered for local treatment. Factors indicating a poor prognosis can be identified histologically by "total biopsy". Definitive management depends on the postoperative tumor stage, type, histologic grading, lymphatic invasion and incomplete surgical excision. Survival rates after limited procedures or radical surgery do not differ, provided that clinical and histologic criteria are observed. PMID- 2577624 TI - [Pouch formation in resection of deep rectal cancer: a recommendable method?]. AB - A degree of urgency and increased bowel movements are experienced by 25% of patients who have a low colorectal or coloanal anastomosis. The construction of a J-shaped colonic pouch seems a reasonable way to improve reservoire continence. We used this new technique in five patients and worked up the preliminary results in connection with a survey of the literature. Increased bowel movements and urgency were reduced postoperatively, but some patients reported pouch evacuation problems, having to use enemas or suppositories to empty their reservoirs. To estimate the value of this new technique, innovative endpoints such as overall well-being and quality of life, might be more important than conventional endpoints which measure only functional results. PMID- 2577625 TI - [Basic principles of rectal excision]. AB - Rectal excision has decreased by half in favour of anterior resection of the rectum. The following points should be observed during operation: (1) dissection close to the rectal wall to avoid injury to the sacral veins and nerves for both bladder and sexual function; (2) ligature of the sup. rectal artery; ligature of the inf. mesent. artery has not been established to be advantageons; (3) avoidance of tumor perforation; (4) primary occlusion of the sacral cavity with extravulnar suction drainage. The results are as follows: 5-6% death rate in the literature and 2.4% in our own patients; bladder dysfunction in 3.5-59%; sexual dysfunction 14-36%; impotence 14-28%; local recurrence 39-57% with and 34% without perforation. PMID- 2577626 TI - [Value and complications of pre- and postoperative radiotherapy from the viewpoint of the surgeon]. AB - If radical surgery of rectal cancer can achieve local/regional recurrence rates lower than 15%, preoperative radiation will not improve these results. If the tumor cannot be removed radically, radiation should be used for tumor reduction. Up until now survival could be improved only with a combination of postoperative radiation and chemotherapy, which was associated with higher complication rates. Here controlled studies are needed. The postoperative radiation must be accounted for in the primary operative concept. PMID- 2577627 TI - [Indications for construction of stoma pouches]. AB - Despite the advances of reconstructive surgical techniques, there are still indications for enterostoma constructions. Terminal colostomies are constructed after abdominoperineal rectal amputations. The terminal ileostomy is the procedure of choice after total colectomies for Crohn's disease. Loop colostomies are still a possibility for stool diversion procedures and for decompression in acute colonic obstruction. Loop ileostomies reduce load before ileal anastomoses and are increasingly used as diverting stomas in cases of colonic anastomoses. The cecal tube fistula, which does not divert the fecal stream completely, has the special advantage of easy, spontaneous closure. PMID- 2577628 TI - [The continent stoma]. AB - Stomatic continence is not comparable to the complicated system of the anorectal organ. Therefore, the definition of continence is ability to arbitrarily determine defecation but with some restriction. It further means the nonreliance on a stoma bag for the intervals between defecation. Continence is achieved by special diet, irrigation, laxatives and clysters. It can be supported by passive and active implants as well as surgical techniques which use smooth and striated muscle functions to imitate, to a certain extent, the muscular components of the anorectal organ. PMID- 2577629 TI - [Quality of life after surgical interventions--vascular surgery]. AB - Vascular surgery is primarily a reconstructive discipline that contributes appreciably to the patient's quality of life (QL) by improving many organ and system functions. The definition of QL includes a variety of specific and very individual aspects. The postoperative evaluation of QL must be based on the one hand on hard data and common clinical parameters, and, on the other, on the individual feeling of the patient, who compares preoperative sequelae and postoperative functional improvement. PMID- 2577630 TI - [The value of irrigation]. AB - Twenty percent of our patients who have had colostomy use irrigation to regulate the bowels. This decision is made by the patient himself after careful deliberation. By means of an irrigation set the large intestine is irrigated with approximately 1-1.5 l of water at body temperature. Subsequently there is a stool free period of 24-28 h and a reduction of flatulence. The duration of irrigation is 45-60 min. Side effects are occasionally pressure sensation and mild convulsive symptoms, but there are no significant complications. Irrigation can begin after complete healing of the stoma, but is absolutely contraindicated in inflammatory intestinal diseases and relatively contraindicated in prolapse, hernia, stenosis, and intestinal damage by radiation. PMID- 2577631 TI - [Value of the stoma therapy specialist in the clinic]. AB - In clinical centers in which colorectal surgery is carried out, stoma therapy units should be set up. The stoma therapist is the most important partner of the surgeon in providing pre- and postoperative care, and giving instruction and information to stoma patients and their relatives. For various reasons, this has been realized only insufficiently but has been implemented in some cases. It should, however, not be overlooked that further developments in stoma therapy have meanwhile had positive effects in other fields of surgery and nursing. Engaged stoma therapists have not only assisted surgeons in patient care but have also imparted new knowledge and shown competence in surgical therapy. PMID- 2577632 TI - [Value of ambulatory clinic-associated stoma therapy, analysis of expenses, success and cost effectiveness from the public economic viewpoint]. AB - A pilot project providing ambulant, hospital-associated stoma care for the affected patients both in the hospital and at home has been in progress in the Kiel/Neumunster area since 1982. An evaluation of the stoma therapist's activities in 1988 and a survey in 1989 demonstrated that patients and family physicians are increasingly accepting the project. Besides a markedly better quality of life, a cautious cost analysis is proved that more than DM 200,000 can be saved annually by avoiding hospitalization and adapting the care system to the needs of the patients. PMID- 2577633 TI - [Pathophysiology of pelvic floor insufficiency]. AB - The muscles of the pelvic floor form a complexly built sustaining structure, which bears the whole weight of the visceral column. The pelvic floor is reinforced by a supporting framework of fasciae. Some of the pelvic muscles are important sphincteric elements for occlusion of the anal canal, the vagina and the urethra. Any weakening of the ingenious construction of the pelvic diaphragm consequently reduces its functions of support or continence. Possible effects are visceral prolapse and incontinence. PMID- 2577634 TI - [Diagnostic measures in anal and rectal prolapse]. AB - As incontinence and outlet obstruction are major problems for patients with anal and rectal prolapse, the following diagnostic procedures are used in addition to the usual examination to plan a more selective therapy and followup: measurement of anal pressure, EMG, anal reflex latency and proctogram. PMID- 2577635 TI - [Surgical methods in anal and rectal prolapse]. AB - Anal prolapse in adults is cured by the Milligan-Morgan procedure. Operation for the rectal prolapse has to repair procidentia, incontinence and obstipation. Procidentia and incontinence in low-risk patients are best repaired by abdominal rectopexy with or without plastic materials (Ripstein's procedure is preferred). Obstipation remains a long-term problem. Rectopexy in combination with sigmoid resection (Goldberg) improves obstipation, but there is leakage in 4% of the patients. The perineal approach offers no technical advantage. Perineal rectopexy, prolapse resection and Thiersch ring with modifications are preferred in high-risk cases. Posterior levator plastic improves remaining incontinence. PMID- 2577636 TI - [Perineal resection of rectal prolapse in risk patients]. AB - A method for perineal resection of rectal prolapse in high-risk patients which uses a circular stapling device was evaluated. After the external rectal layer was dissected 2 cm above the dentate line, the sigmoid colon was mobilized distally as far as possible. An anastomosis was then performed with the stapler under gentle tension on the sigmoid colon. None of the eight patients died; mucosal prolapse recurred in one patient. Continence was improved in six of the eight patients. PMID- 2577637 TI - [Anatomy and pathophysiology of hemorrhoids]. AB - The internal (hemmorrhoidal) plexus consists of two groups of veins separated by the musculus canalis ani. The submucosal group forms the zona hemorrhoidalis. A direct communication between arteries and veins is the characteristic sign of this functional part of rectal circulation. In the nutrient part, the arterioles divide into capillaries. The vessels of the zona hemorrhoidalis are wrapped in by a system of elastic fibers, which split with age. Common pathogenetic factors of hemorrhoids may involve the spasm of anal sphincters and the absence of elastic fiber support of the plexus. PMID- 2577638 TI - [Surgical progress and quality of life--plastic surgery]. AB - Since its beginnings, Plastic surgery has aimed to restore not only physical health but also self-esteem and thereby contribute to the patient's healthy frame of mind. Special attention is paid to restoring the psychosocial function of normal appearance. Plastic surgery also contributes to the quality of life by what has exaggeratedly been called "psychotherapy with the scalpel". PMID- 2577639 TI - [Surgical techniques and long-term results for hemorrhoids from the clinical viewpoint]. AB - The decongestion of the hemorrhoidal cushion is the main principle in treating piles. This is achieved with a diet high in roughage. Although severe hemorrhoids are not cured by buld-forming agents, they are of central importance to prevent recurrences. Hemorrhoidectomy should be performed mainly in cases of hemorrhoidal prolapse. Results of the three most often used techniques (Milligan-Morgan, Parks, Ferguson) are more or less comparable, although the presentation of the details in the literature is contradictionary. Each surgeon should use the technique that suits him best. We prefer the closed operation described by Ferguson. PMID- 2577640 TI - [Diagnosis and principles of treatment for fissure in ano]. AB - The diagnosis of an anal fissure can be made definitively on the basis of history and inspection. Therapy aims to stop the vicious circle of increased resting pressure, decreased perfusion, pain and obstipation. Chronic fissures are complicated by an incomplete fistula-in-ano. It is treated by laying open the fistula and sphincterotomy. PMID- 2577641 TI - [Diagnosis and treatment of anal fistula]. AB - Anorectal fistulas can only be cured by operative treatment based on a thorough knowledge of anal anatomy. Recurrences are frequently a result of the surgeon's failure to expose the entire fistula tract out of fear of impaining anal continence. Surgery can provide a permanent cure in 95% of all such cases. Curative treatment of fistulas in patients with colitis, Crohn's disease or AIDS may not be feasible, but some improvement can be achieved. Anal sphincter function should be measured prior to surgery. The anal sphincter is always stronger in males than in females, who are more likely to experience permanent damage of anal continence. This is also true for patients with recurrent disease. Some cases of complicated fistulas are reported. PMID- 2577642 TI - [Responsibility of the surgeon in intensive care units]. AB - Intensive care facilities in most hospitals are concentrated in one or more specialised units. There are different forms of organisation. The leadership of the surgeon or the anesthesiologist is common in operative intensive care. However, operative intensive care is an interdisciplinary task, and the surgeon is responsible for all problems connected to or resulting from the operation. PMID- 2577643 TI - [Intensive care--forensic problems from the viewpoint of divided responsibility]. AB - The agreements between surgery/anesthesiology (1970) differentiate between specialist and indisciplinary intensive care units. In the specialist unit the surgeon is also responsible for intensive care therapy. In the interdisciplinary units the surgeon is responsible for the treatment of the primary disease and the anesthesiologist is responsible for the intensive care therapy. Their cooperation is determined by a strict division of labor and the principle of confidence. The agreements, which have proven successful legally, leave the decision about a more detailed delimitation of the tasks to local arrangements. It is suggested that a concretization of the agreements of 1970 should perhaps be considered. PMID- 2577644 TI - [Score systems, their importance for the intensive care patient]. AB - Scoring systems are a technique for defining patients for scientific and management purposes. A hypothetical, severely ill patient with cirrhosis, peritonitis, renal insufficiency and coagulation problems can be precisely classified: Child C, Mannheim-Peritonitis-Index 34 and APACHE II score 27 which results in a mortality of at least 70% of patients. At our own hospital, the continuous APACHE score (CAPS) has been developed and tested. The CAPS performed better than daily APACHE scores and provided useful trend information for the individual patient. PMID- 2577645 TI - [Treatment of infection in intensive care patients]. AB - A basic prerequisite of successful treatment of sepsis in intensive care patients is early recognition. Aside from the classic clinical signs of infection, minute changes in volume demand, respiratory need, kidney function and cardiovascular regulation may indicate a septic complication. The surgical/mech. elimination of septic foci is still the paramount therapeutic principle. Volume and respiratory therapy, hemofiltration, cardiovascular and antibiotic medication may add to the standard procedure of intensive care. Contact site inhibitors, mediator antagonists, and antibodies targeted against endotoxin, bacteria or leukocyte surface antigens are either still controversial or undergoing preclinical evaluation. PMID- 2577646 TI - [Pulmonary complications within the scope of multiple organ failure]. AB - The adult respiratory distress syndrome (ARDS) is the pulmonary manifestation of multiple organ failure. Respiratory distress, alveolar consolidation and hypoxemia refractory to oxygen are the result of uniform and unspecific morphological reactions of the alveolo capillary membrane. The development of ARDS is most commonly associated with risk factors such as sepsis, trauma, shock or pneumonia. A causal therapy for ARDS is not known. Treatment of the underlying disease, maintenance of arterial oxygenation and prevention of secondary complications are the most important therapeutic measures. PMID- 2577647 TI - [Primary rehabilitation of the burn patient]. AB - The treatment of burn victims in a specialized fully equipped center with specialized staff has as its goal the primary, definitive, somatic and psychosocial rehabilitation, of the patient. Not only are the chances of survival to be increased, but an optimal quality of life is to be restored. PMID- 2577648 TI - [Primary excision of third degree burns]. AB - Fresh third-degree burns with a diameter up to that of a hand should be excised primarily and the wound edges closed under tension. Fasciocutaneous flaps can be designed for wound closure especially on the extremitites. This treatment requires half the time of skin grafting. Since patients with huge burn areas often react with hypertrophic scarring for years, a simple reduction of the areas by wide excision and closure under tension appears to be the method of first choice. In contrast to scar tissue healthy skin has a natural ability to stretch when wound margins are closed under maximal tension. The efficacy of possibilities is proven by the many favourable results. PMID- 2577649 TI - [Reconstruction of the cranial vault and soft tissues of the skull after electrotrauma]. AB - Of 550 patients treated in our burn unit 5.1% had electrical injuries. Injuries of the skull and scalp were caused by entry of electrical current. The classic reconstruction of the scalp and skull is performed after sequestration of the necrotic bone, a time-consuming process which frequently has complications. An alternative is to induce regeneration of the vitalized bone by covering it early with a vascular tissue flap. Skeletal scintigraphy has the advantage of allowing early and safe assessment of the vitality of the injured bone and helps to control vitalization. PMID- 2577650 TI - [Quality of life after surgical interventions in pediatrics]. AB - Quality of life is a complex entity without "normal finding" and can be judged by objective and subjective criteria. Quality of life of a child results out of the main factors which are connected to each other and represent the actual specific profile of a personality. The disease or dysplasia itself, personality of the patient, personality of the attending physician as well as of the parents. Quality of life of a child consists of five interwoven spheres: bodily function of the child; psychological well-being; social interactions; physical state; and parents. PMID- 2577651 TI - [Immediate functional reconstruction of the upper extremity after high voltage electric burns]. AB - Large soft tissue defects on the upper arm and the forearm of a 14-year-old boy caused by electrical trauma were repaired with a free latissimus dorsi flap on the left forearm and a neurovascular lat. dorsi island flap to the right upper arm. Both extremities were saved, the defects covered and good functional repair was achieved. The latissimus dorsi flap is a save and easy procedure with a high variability. It is especially suitable for primary repair of large soft tissue defects. PMID- 2577652 TI - [Limits in the possibilities for rehabilitation of lye burns of the face]. AB - Several cases of lye burns of the face are presented. The most common causes are explosions. Primary treatment includes continuous irrigation, debridement by dermabrasion and split-thickness skin grafts. The problems resulting from deep burns with loss of the eyelids and exposure of the alar cartilages, can be solved satisfactorily only with distant pedicled flaps. PMID- 2577653 TI - [Procedures in reconstructive interventions in the area of the face and neck after burn injuries]. AB - Hypertrophic scars and tissue defects are the most common cause of functional and aesthetic problems in the head and neck of burn patients. For reconstructive surgery full-thickness or split thickness skin grafts are preferred. Pedicled flaps or free flaps are mostly used to correct contractures in the neck. The transplantation of bone or cartilage and tissue expansion are also used for special indications. PMID- 2577654 TI - [Serial excision of large surface burn scars]. AB - Serial excisions of large defined burn scars often improve the aesthetic appearance as well as reduce subjective complaints such as itching and sensory disturbance. The natural elasticity of undamaged skin allows stepwise excision of areas up to the size of a hand. Ideally, a linear scar the length of the original scar area results. Shrinkage, contour and pigment deficiencies, often seen after skin grafting, are not a problem. PMID- 2577655 TI - [Plastic correction of thoracic wall burns with reference to the female breast]. AB - Neck and shoulder contractures, large scars of the thoracic wall and breast defects require plastic surgery. If possible, local flaps are the best solution for contractures, eventually enlarged by skin expanders. Full thickness skin grafts, Z-plasties and simple excisions with primary wound closure are alternative methods. For breast reconstruction early skin grafts or secondary local flaps are used. Myocutaneous flaps from the latissimus dorsi or rectus abdominis are seldom indicated. PMID- 2577656 TI - [Reconstructive possibilities after burns of the female breast]. AB - Reconstruction of the adolescent female breast after full-thickness burns differs from that of the mature female breast. Whereas a final correction is aspired to in the adult, the operative procedure should be adjusted to the evolution of the breast in the adolescent. Our therapeutic guidelines as well as the advantages and disadvantages of the different procedures are discussed. PMID- 2577657 TI - [Burn sequelae of the hand and face, when full-thickness skin transplant, when flap?]. AB - Full-thickness skin grafts if possible and flap plasties if necessary are our common guideline for reconstruction of the face and hands after burns injuries. If the mobility of the lips, the eyelids or the fingers is limited by contracted scars, the interposition of full-thickness skin grafts is generally very helpful. This is also true for the face and the hands. Flaps are necessary for the hands if there are tendons to be covered or joints to be closed. PMID- 2577658 TI - [Timing indications for plastic surgery interventions in burns in the area of the neck and across joints]. AB - From 1985 to 1988, 120 patients underwent opertations. 200 times because of deep dermal or total dermal thermal injury. On the basis on the pathophysiology of tissue repair and scar contracture after burns as well as our experience we conclude that the first aim of the surgeon should be to avoid granulation tissue, the precursor of contracting scars. Only the immediate transplantation of autologous skin onto the surgically created wound after excision of burned tissue can halt the repair process. Flaps are the treatment of choice for reconstruction of existing contracturs deep in the fascia. PMID- 2577659 TI - [Corrective osteotomies of the thigh after faulty healing of infected burn wounds]. AB - The occurrence of burn injuries and fractures of the extremities often necessitates that vital precautions be taken first and the possibility of osseous defective healing be initially accepted. After the vital functions have been stabilized, late corrective procedures become necessary. Two cases of the treatment strategy for femur fractures which healed defectively are reported. PMID- 2577660 TI - [Corrective possibilities of burn contractures of the large joints]. AB - Major joint movement is frequently limited following full-thickness burns of the extremities due to scar contractures. After operative correction of the contractures physical therapy is absolutely necessary. Skin contractures are treated with Z-plasty, skin graft, local flaps, pedicled flaps and free tissue transfer. The advantages and disadvantages of those procedures are described. PMID- 2577661 TI - [Pathology of premalignant and malignant diseases of the female breast]. AB - There are three frequent, basic diagnoses of breast lesions: fibroadenomas, fibrocystic diseases and carcinomas. The atypical fibroadenoma, the phyllodes tumour, the atypical ductal and/or lobular hyperplasia and the atypical papilloma are important because they may be a premalignant condition. For therapy it is important to know that the non-invasive carcinomas are often plurifocal, multicentric and bilateral. Women with manifest invasive breast cancer have a very high risk of contralateral cancer, but generally the cancer on the opposite side is microfocal. PMID- 2577662 TI - [Indications, technique, results and value of breast saving surgery in breast cancer]. AB - Breast preservation is by no means a standard treatment modality for breast cancer. An increasing number of unsatisfactory results have been observed despite the fulfillment of requirements necessary for adequate treatment. Excellent surgical technique is a solid basis for good cosmetic result. According to the interim analysis of the German breast preservation study a tumor biopsy with a small margin of healthy tissue together with a lower axillary dissection can be considered a sufficient surgical procedure. The relationship between tumor size and size of the breast is one of the most important factors determining contraindications for breast preservation. Adequate instruction of the patient still remains a major problem for most doctors. If the patient is properly informed about the operation quality of life is not substantially altered after mastectomy and breast reconstruction compared with breast preservation therapy. PMID- 2577663 TI - [Indications, technique, results and value of modified radical mastectomy]. AB - Modified radical mastectomy is the most frequent operation performed for therapy of primary breast cancer. In T1 breast cancer patients the breast-conserving therapy is used in up to 40-60% of the patients. In T2 breast cancer patients modified radical mastectomy is still the most frequently used regimen (72-79%). Tumor, breast and psychological characteristics as well a technical facilities must be considered, when determining if modified radical mastectomy is indicated. The operation technique is presented. PMID- 2577664 TI - [Mastectomy and primary breast reconstruction]. AB - Primary breast reconstruction after mastectomy may be proposed individually after careful consultation of the patient. Whereas postoperative chemotherapy or hormone therapy are not contraindications, radiotherapy is a relative contraindication. Methods include the submuscular silicone implant (+/- expansion), mobilisation of the abdominal skin or flap reconstruction (thoracoepigastric or latissimus flap). The indications, pros and cons, are discussed. Mastectomy and primary reconstruction are good alternatives to the so called conservative treatment with irradiation. PMID- 2577665 TI - [Surgical procedure for secondary breast reconstruction after mastectomy]. AB - The type of reconstruction is determined by the mastectomy deformity and requirements for symmetry. There are five basic techniques. A silicone breast implant placed submuscularly beneath the available tissues is the most straight forward procedure. Latissimus dorsi flap is used with a silicone breast implant when additional skin and/or muscular cover is needed. Transverse rectus abdominis musculocutaneous utilizes excess lower abdominal tissue for reconstruction of the breast with autogenous tissue. The tissue expander is most frequently used following modified radical mastectomy. The external oblique rectus abdominis musculofascial turn-over flap is an attractive new technique. PMID- 2577666 TI - [Treatment of radiation sequelae after breast cancer]. AB - Defects of the chest wall after radiation for carcinoma of the breast cannot be closed by means of simple split-skin graft or compound flaps because of the decreased blood supply. Only transposition flaps will survive because of their own vascularisation. Musculocutaneous flaps, the latissimus island flap or the vertical or transverse rectus abdominis-flap, which also can be used for the reconstruction of a bid pendolous breast, are the safest. PMID- 2577667 TI - [Surgical indications in severe abnormalities with reference to the expected quality of life]. AB - An explanation of the term "quality of life" must consider the view of the person concerned, the view of the therapist and society. Patients with MMC who have the prerequisites for a satisfactory quality of life are often unable to realize it in practice. Prenatal diagnostics has not yet provided new indications for operation. The malformation in the seven last admitted children with MMC was not known before the 23rd week of pregnancy. A selection after birth is considered problematical. PMID- 2577668 TI - [Progress in surgery and quality of life, quality of life after organ transplantation]. AB - Kidney and liver transplantations are well established surgical procedures. During the past years survival rates have improved 3% of kidney transplantations have 1-year mortality. Subjective quality of life and professional rehabilitation are associated with the graft function parameters of successful therapy. Seventy six percent of liver-transplanted patients consider their quality of life improved after the operation. 52% are able to return to work. Future efforts must focus on improving immunosuppression for specific tolerance and sensitizing the public to the problems of obtaining organs for transplantation. PMID- 2577670 TI - [Short bowl syndrome and quality of life in childhood]. AB - From 1985 to 1988, six patients suffered from short gut syndrome due to congenital malformations. The children were aged 4-24 months at the time of the operation in which the gut was doubled in length by a Bianchi procedure. It is necessary to interview the parents about their own and the child's psychological and physical stress during the pre- and postoperative periods. Collective reactions were found which must be considered for indication and time of operation. PMID- 2577669 TI - [Esophageal atresia and quality of life]. AB - To evaluate the quality of life of patients with esophageal atresia 122 questionnaires about children who underwent operations in several centres in the Federal Republic of Germany were analysed. On the basis of this information, the literature and our own cases, we found that these patients early childhood is complicated by operations, dilatations, difficulties of swallowing and frequent pulmonary infections. These problems improved in most cases during the first years of life. Subsequently the quality of life can be regarded as good. PMID- 2577671 TI - [Bladder exstrophy and quality of life]. AB - The primary objectives of operative management of exstrophy of the urinary bladder are to obtain secure closure of pelvic girdle and abdominal wall, unimpeded voiding, urinary continence, absence of reflux, preservation of renal function, functional and cosmetically acceptable external genitalia, and the absence of malignancy. These objectives cannot be fully achieved by only one of the established procedures such as functional bladder closure, internal or external urinary diversion and epispadias repair. Early individual and creative surgical management including changing concepts when needed and careful life-long followup are thought to provide the basis for a satisfying social adjustment and quality of life. PMID- 2577672 TI - [Long term results and quality of life of children with omphalocele and gastroschisis]. AB - Thirty-six children who underwent operations for omphalocele or gastroschisis were followed up at an average age of 7.4 years by medical examination. The majority of those who survived the initial treatment showed no signs of physical or psychological disorder linked with their abdominal wall defects. Those children without severe associated malformations were able to conduct a normal life. PMID- 2577673 TI - [Initial measures in newborn infants with surgically correctable abnormalities]. AB - In newborns with surgically correctable malformations the quality of primary care has considerable influence on the results of the eventual surgical repair. This is particularly true for extensive diaphragmatic and abdominal wall defects as well as for esophageal and intestinal atresia, exstrophy of the bladder and urogenital malformations. The neonatal management comprises measures generally valid for all diseased newborns and measures specific for the particular malformation. The general care concerns heat regulation, fluid balance and other vital functions. Specific regimens are necessary as primary care for diaphragmatic hernia, esophageal atresia, abdominal wall defects and neonatal bowel obstruction. Furthermore this primary management must be extended to include the care of the pregnant mother. Already in utero infants with diaphragmatic and esophageal malformations should be referred to the gynecological-neonatal center. PMID- 2577674 TI - [Complications after surgical interventions in the neonatal period and their relevance for quality of life]. AB - In a retrospective study the postoperative course was examined of 296 neonates who had a birthweight of more than 1500 g and a congenital malformations between 1981 and 1987. A questionnaire was sent to the parents of the 242 surviving children in which they were asked about their children's current quality of life (average age 5.3 years). Of the 151 parents responding, 42% were of the opinion that the quality of their children's life had been reduced. The main reason was the operated malformation or accompanying illnesses. Only in 5% of the cases were postoperative complications considered responsible for the decline in quality of life. PMID- 2577675 TI - [Partial continence and quality of life]. AB - Incontinence, even if it is only partial, always affects quality of life. The degree of suffering differs in the various age groups. The young child suffers mainly from localized painful lesions, the older child due to environmental factors. For adolescents, the range of professional and interpersonal options is greatly restricted. The task of the pediatric surgeon is to influence positively the quality of life by means of a carefully planned primary operation, appropriate corrective procedures and psychological supportive measures. PMID- 2577676 TI - [The importance of primary operation for continence]. AB - Between 1962 and 1987, 434 patients with anorectal (AR) malformations underwent operations at the hospital for sick children in Cologne. On the basis of continence results from these patients, the influence of the primary operation on postoperative anorectal continence is discussed. It can be concluded that a number of operations used in earlier times such as the cut-back procedure, the primary or secondary abdominoperineal pull-through procedure, should not be used with the advent of more detailed and sophisticated radiologic investigations and never anatomyrelated surgical techniques, AR continence results can be improved. The anatomical principles of these primary procedures are discussed. PMID- 2577677 TI - [Improving continence by reoperation]. AB - Between 1969 and 1988, 191 children underwent operations for anorectal anomalies in the Pediatric Surgical Department of Mainz University Hospital. Ninety-six had deep and 84 had intermediate or high malformations; the type was unknown in 11. Of these patients 53 had impaired continence and 8 still have a protective colostoma. 37 of the remaining 45 children had check-ups and reoperations (5 were deep types). After reoperation there was full continence in 14 patients, partial continence in 11, persisting incontinence in 11 and one case could not be assessed. Our results recommend reoperation using modern surgical methods of patients with continence. PMID- 2577678 TI - [Improving continence by biofeedback conditioning]. AB - In the last 10 years biofeedback training (BFT) has been used in 72 patients with anal continence disturbances following rectoanal agenesis, constipation, MMC, etc. Using the BF-method we treated 35 children with incontinence following rectoanal agenesis (5 infralevator, 30 supralevator). Visual analog feedback was used in the first 10 cases. Since 1982 simultaneous audiovisual analog signals have been preferred. The detailed analysis and personal followup over 6.5 years of these patients suggests that BFT improves the threshold of rectal sensation, voluntary contraction and thereby benefits anal continence. PMID- 2577679 TI - [Biofeedback training and functional electrostimulation for improving incontinence in children with anal atresia]. AB - Eleven children with anal incontinence following a pull-through operation for anorectal agenesis (4 low, 7 high anomalies) were treated with a conservative continence training program (optic/acoustic biofeedback, transcutaneous electrical stimulation, physical therapy, contraction exercises and sensibility training). All patients with one exception showed subjective and objective improvement of continence. Sphincter contraction increased by 80% in high and by 40% in low anomalies. For a short time electrostimulation provided an improvement of up to 20% in sphincter pressure. One additional success was improved coordination. Beside surgical therapy and other methods continence training is always indicated. PMID- 2577680 TI - [Anorectal abnormalities--incontinence and abnormalities]. AB - The quality of life of incontinent patients was analysed in a group of 494 children treated over 20 years. The ratio of incontinent children was constant above an age of 10 years. Incontinence correlates with social status of the family; it is better in single children and worse in single-parent families. School outcome and professional status is significantly better for continent patients. The main problems of the children and adults were analysed. Compensatory mechanisms and the importance of early care of incontinent patients are mentioned. PMID- 2577681 TI - Composition of nerve biomembranes and nutritional fatty acids. PMID- 2577682 TI - Beta 2-adrenoceptor stimulation inhibits ganglionic transmission in ferret trachea. AB - To study the effect of beta-adrenoceptor stimulation on the transmission through airway parasympathetic ganglia, we used an in vitro nerve-muscle preparation of ferret trachea. Isometric muscle contractions were induced for 20 s every 2 min alternating with postganglionic activation by electrical field stimulation (EFS) or with preganglionic activation by direct nerve stimulation (DNS). The pulse frequency was always 12 Hz. A possible modulation of ganglionic transmission was assessed by comparing contractions induced by DNS to contractions induced by EFS. In 9 experiments isoprenaline initially reduced the response to EFS and DNS to the same extent, indicating an effect on postganglionic structures. After 20-30 min exposure the response to preganglionic activation by DNS was further reduced indicating an inhibition of ganglionic transmission. The concentration/response relationship for the ganglionic effect of isoprenaline was shifted about ten times to the right by 0.1 microM propranolol (n = 5) and by a beta 2-adrenoceptor antagonist (0.1 microM ICI 118.551) (n = 8), whereas a beta 1-adrenoceptor antagonist (10 microM practolol) had no, or only slight, effect. In two experiments pretreatment by 0.1 microM phenoxybenzamine for 20 min did not prevent ganglionic inhibition by 0.3 microM isoprenaline. We conclude that parasympathetic ganglia in ferret trachea have beta-adrenoceptors mediating inhibition of ganglionic transmission, and that these probably are of the beta 2 type. Tentatively these receptors could be operated upon by circulating catecholamines. PMID- 2577683 TI - Radio-immunoassay of somatostatin from isolated rat pancreatic islets. AB - Certain aspects of radio-immunoassay of somatostatin from isolated rat pancreatic islets are described. Somatostatin-14, and not somatostatin-28, is secreted from isolated rat pancreatic islets. Less somatostatin secretion is measured per islet owing to purity of tracer in the radio-immunoassay. Theophylline apparently cross reacts with somatostatin in the assay described, and this has to be taken into consideration when studying somatostatin release induced by theophylline in isolated islets. PMID- 2577684 TI - Somatostatin secretion from isolated rat pancreatic islets. AB - Certain aspects of somatostatin secretion from isolated rat pancreatic islets are described. A considerable, but falling basal secretion of somatostatin was observed in the pre-incubation periods. Both glucose and theophylline stimulation gave significant increases in somatostatin secretion, whereas carbachol inhibits the somatostatin secretion at 25 mmol l-1 glucose but not at 5 mmol l-1 glucose. The glucose effect on somatostatin secretion required a normoglycaemic pre incubation level of 5.5 mmol l-1 glucose. Our results indicate that somatostatin secretion from isolated pancreatic islets is strongly dependent on the experimental conditions. PMID- 2577685 TI - Symposium: The Practicing Physician's Approach to the Difficult Headache Patient. Cincinnati, April 16-17, 1988. PMID- 2577687 TI - Acute pain service. Symposium. Washington, D.C., September 10, 1988. PMID- 2577686 TI - Lidocaine treatment of painful diabetic neuropathy and endogenous opioid peptides in plasma. AB - Intravenous infusion of lidocaine has a pain-relieving effect in patients with painful diabetic neuropathy. We measured plasma beta-endorphin (beta-EP), dynorphin immunoreactivity (DYN), and met-enkephalin (MET) before and after lidocaine infusion in 8 patients with painful diabetic neuropathy and in 10 controls. The pretreatment level of beta-EP and DYN was identical in the two groups. After lidocaine, beta-EP increased in diabetic patients from 3.4 to 5.5 pmol/L (median) (p less than 0.02) and in controls from 3.4 to 5.0 pmol/L (p less than 0.02). The concentration of DYN was stable, and MET was undetectable before and after lidocaine. Lidocaine reduced symptoms and pain score in diabetic patients was uncorrelated with the changes in beta-EP. Intravenous lidocaine increased plasma beta-EP and diminished complaints in patients with painful diabetic neuropathy. PMID- 2577688 TI - Pharmacology of narcotic analgesics. AB - Opioid receptors are described and differentiated by their affinities for specific agonists and antagonists. Their sites of action and receptor activities are discussed. Tachyphylaxis and tolerance are described and methods for overcoming these problems are recommended. Suggestions are made regarding future drugs to act at specific receptors. PMID- 2577689 TI - The distribution and ontogeny of gastrin/CCK-, somatostatin- and neurotensin immunoreactive cells in the gastrointestinal tract of the chicken. AB - The distribution and time of appearance of cells with gastrin/CCK-, neurotensin- and somatostatin-like immunoreactivity were studied in samples from eight regions of the gastrointestinal tract of chick embryos from 11 days of incubation to hatching. No immunoreactive cells were found in any region at 11 days of incubation. Somatostatin- and neurotensin-immunoreactive cells appeared for the first time in the proventriculus, pyloric region and duodenum at 12 days of incubation with cells immunoreactive for neurotensin occurring in the rectum at the same stage. Gastrin/CCK-immunoreactive cells were detected in the small intestine first at 14 days and in the pyloric region two days later. Cells immunoreactive for somatostatin and neurotensin appeared in the upper and lower ileum at 14 days of incubation for the first time; neurotensin-immunoreactive cells, present in the caecum at 14 and 16 days, were rare. Cells of all three types were plentiful in the pyloric region by 17 1/2 days of incubation. No immunoreactive cells were detected in the gizzard at any stage studied. Endocrine cells were present in the relatively undifferentiated surface epithelium which occurs throughout the gastrointestinal tract of chick embryos at 12 days of incubation. Thereafter cells of all three types were detected in the glandular epithelium at or very soon after morphogenesis and differentiation of the latter had occurred. PMID- 2577690 TI - Reduced responsiveness of bronchoalveolar cells from sensitised guinea-pigs to the cyclic AMP--stimulating effect of prostaglandin E2 and beta-adrenoceptor agonists. AB - Prostaglandin E2 and the beta-adrenoceptor agonist salbutamol were less effective in increasing the intracellular cAMP content of bronchoalveolar cells and adherent alveolar macrophages from ovalbumin-sensitised as compared to control guinea-pigs. This refractoriness to the cyclic AMP-stimulating effects of PGE2 and salbutamol induced by the sensitisation procedure may be relevant to the altered bronchopulmonary responsiveness in asthma. PMID- 2577691 TI - On the predictive value of experiments in vitro in the evaluation of the effect duration of bronchodilator drugs for local administration. AB - Six bronchodilating beta-adrenoceptor agonists, clinically documented with respect to the duration of action after inhalation, were included in this study in vitro on the guinea-pig trachea. Relaxation of carbachol contracted trachea strip preparations and inhibition of contraction of a vagus nerve-tracheal tube preparation were measured. The relaxing effects of salbutamol and fenoterol (both with relatively short duration in man) were rapid in onset and easily reversed by washing in a drug-free medium. The relaxation by salmeterol (long duration) and D2343 (intermediate duration) developed more slowly, resisted washing but was reversed by propranolol. Formoterol (long duration) and salmefamol (intermediate duration) showed properties between these two extremes. All test compounds inhibited the vagally-induced contractions of tracheal concentration dependently. The EC50 values for the hydrophilic compounds salbutamol and fenoterol were higher with intra- as compared with extratracheal administration. For the more lipophilic compounds formoterol, salmefamol, salmeterol and D2343, this difference was less pronounced. A high lipophilicity and a retention by the tissue in vitro of a beta-adrenoceptor agonist may be factors contributing to a long effect duration after inhalation but a further selection has to be made in vivo since metabolic and circulatory effects may influence the effect kinetics. PMID- 2577692 TI - Effects of dilevalol, a beta-adrenoceptor antagonist with intrinsic sympathetic activity in asthmatic patients. AB - The effects on baseline ventilation as well as beta 2-receptor stimulant-induced bronchodilation and tremor of atenolol and dilevalol, a beta-blocking agent with non-selective beta-antagonistic properties and intrinsic activity on the beta 2 receptor were evaluated in 8 patients with stable asthma. Both atenolol and dilevalol were found to significantly decrease both forced expiratory volume during 1 s (FEV1) and forced vital capacity (FVC). This decrease was significantly more pronounced after atenolol. Both agents decreased systolic and diastolic blood pressure as well as heart rate to a similar degree. Increased activation of beta 2-adrenoceptors by terbutaline infusion resulted in increased FEV1 and FVC as well as beta 2-adrenoceptor mediated reflex tachycardia and skeletal muscle tremor. The dose response curves for all these parameters were significantly shifted to the right and a decrease of the maximum relative response was seen after atenolol pretreatment. This effect was more pronounced after treatment with dilevalol with a further shift to the right of the response curve and a decrease of the maximum relative response. The haemodynamic and ventilatory effects of dilevalol are consistent with a non-selective beta adrenoceptor blockade combined with intrinsic activity on the beta 2-receptors. PMID- 2577693 TI - Closing the window on AIDS. Proceedings of a symposium. New York, New York, April 22, 1988. PMID- 2577694 TI - Effect of BMY-25368, a potent and long-acting histamine H2-receptor antagonist, on gastric secretion and aspirin-induced gastric lesions in the dog. AB - BMY-25368, 1-amino-2-[3-(3-piperidinomethylphenoxy) propylamino]-1-cyclobutene 3,4-dione, a new histamine H2-receptor antagonist, has been compared to ranitidine as an inhibitor of gastric acid secretion in the Heidenhain pouch dog. Intravenous infusion of BMY-25368 antagonized histamine-stimulated gastric secretion in a competitive manner. BMY-25368 also antagonized gastric secretion stimulated by pentagastrin, bethanechol and food. When compared to ranitidine in histamine-stimulated dogs, BMY-25368 was nine times more potent after bolus intravenous administration. Oral potency relative to ranitidine and ranged from 2.8 to 4.4, depending on the secretagogue used. BMY-25368 also exhibited a significantly longer duration of action than ranitidine. Thus, its potency relative to ranitidine after oral administration, in histamine-stimulated dogs, increased from 3.2 to 28 when determined 1-3 and 10-12 h post dose, respectively. BMY-25368 administered orally also antagonized aspirin-induced gastric lesions in the dog and was nine times more potent than ranitidine in this respect. PMID- 2577695 TI - Natural history of Campylobacter pylori in duodenal ulceration treated with an H2 antagonist. AB - Campylobacter pylori has been associated closely with active antral gastritis and duodenal ulcer but its pathogenetic role remains uncertain. The present longitudinal study examined, prospectively, the endoscopic antral biopsies of 45 patients with duodenal ulceration, taken before and after healing of the duodenal ulcer, during remission and at relapse. The biopsies were examined for the activity and degree of chronic inflammation of the gastritis and for the occurrence and density of C. pylori by Warthin-Starry stain. Before treatment the frequency of chronic active antral gastritis was 100% and the occurrence of C. pylori was 97%. Compared with the pre-treatment state, there was no significant change in either the frequency and severity of antral gastritis, or in the occurrence and density of the bacteria in the antral mucosa at the time the duodenal ulcer healed, during remission, or at relapse. The occurrence of the bacteria was significantly more frequent during remission, than at the time when the ulcer had healed initially (P less than 0.05). These results suggest that the bacterium may not play an important pathogenetic role in ulcer healing and relapse, when patients are managed using an H2-blocker. PMID- 2577696 TI - Adverse events of anti-glaucoma beta-blockers: presentation of an original HPLC determination procedure. AB - A HPLC method is described for the identification and quantification in plasma and urine of beta-blockers (betaxolol, carteolol, metipranolol, and timolol) topically used in the therapy of glaucoma. An extraction method is presented using pindolol as an internal standard. Separation is performed on an RSIL CN 10 microns column with a mobile phase of water/acetonitrile/pH 3.0 0.1 M NaH2PO4 buffer solution (60:30:10, v/v). The lower detection limits were found to be 4 to 27 ng/ml. This method is simple, rapid and sensitive; moreover, it allows the determination of 8 other beta-blockers. PMID- 2577697 TI - Novel heptapeptide somatostatin analog displays anti-tumor activity independent of effects on growth hormone secretion. AB - A series of heptapeptide somatostatin (SRIF) analogs containing mercaptopropionic acid (Mpa) and based on the parent structure Mpa-Tyr-[D]Trp-Lys-Val-Cys-Thr-NH2 were synthesized by solid-phase methodologies and assayed for their effects on rat growth hormone (GH) secretion and their ability to displace [125I]Tyr11-SRIF bound to various tissues in vitro. Structural modifications consisted primarily of aromatic substitutions for Thr. All analogs were less potent than SRIF in inhibiting GH secretion in vitro from 4-day primary cultures of rat pituitary cells (0.04-21% that of SRIF). Higher GH inhibitory potencies were observed in an acute 15 min in vivo potency assay probably reflecting increases in plasma half life of the analogs as compared to native SRIF. All analogs had extremely low binding affinity for rat cerebral cortex (0.05-4% that of SRIF), while binding potency for rat pancreas ranged from 3-130% of SRIF. Several analogs exhibited enhanced binding to human small cell lung carcinoma cells (SCLC; NCI-H69) as compared to SRIF. One of these, containing Phe at the C-terminus, exhibited an affinity 3.5 X greater than SRIF itself and was further tested for possible effects on the proliferation of SCLC and rat pancreatic tumor cells (AR42J) in vitro. The proliferation of both tumor types was inhibited 32 and 60%, respectively (p less than 0.01). The data suggest that SRIF and certain analogs may have a direct action on proliferating tumors independent of endocrine effects and that the anti-tumor activity of SRIF analogs can be further dissociated from the other actions of native SRIF, thereby providing for potentially more selective therapeutic analogs. PMID- 2577698 TI - The investigation of Fmoc-cysteine derivatives in solid phase peptide synthesis. AB - Fmoc-Cys(t-Bu)-OH, Fmoc-Cys(Acm)-OH, and Fmoc-Cys(Trt)-OH exhibit excellent synthesis characteristics when used in Fmoc solid phase peptide synthesis on the Applied Biosystems Model 431A peptide synthesizer. The actual 5% scavenger mixture will vary according to the particular amino acid residues present. As was previously mentioned, an anisole/ethanedithiol/ethylmethylsulfide mixture (3:1:1) works well as a general scavenger solution for TFA cleavage of Fmoc synthesized peptide resins. It also may be possible to use lower acid (TFA) concentrations. The syntheses and workups of the peptide Somatostatin utilizing these derivatives demonstrate the ease of using these cysteine derivatives with the Fmoc chemistry approach. The use of either the t-Bu or the Acm moiety produces a peptide containing protected thiol groups after cleavage with 95% TFA. The Fmoc-Cys(Trt) OH derivative is efficiently deprotected using 95% TFA. This investigation should provide further insight into synthesis options and cleavage protocols when working with cysteine-containing peptides. PMID- 2577699 TI - Specific inhibition of bacterial and bovine urocanases by glycylglycine. AB - Urocanase (EC 4.2.1.49) purified from Pseudomonas putida was unexpectedly inhibited by the dipeptide glycylglycine. Using a spectrophotometric assay for urocanase activity, we characterized the inhibition. The inhibition was temperature-, concentration-, and time-dependent; 0.1, 0.5 and 1.0 mM glycylglycine inhibited the enzyme by 20%, 50% and 78%, respectively, in 60 min at 30 degrees C. Dithiothreitol and reduced glutathione did not prevent the process. The inhibition was a pseudo first-order reaction. Three ligands that bind to the active site, urocanate, imidazole-propionate (a competitive inhibitor) and sulfite, protected the enzyme from glycylglycine inhibition. The inhibition was very specific for glycylglycine, because fifteen related biochemicals, including glycine, triglycine, and tetraglycine, were not effective. Ethylenediaminetetraacetic acid and other chelators did not inhibit urocanase. Bovine liver urocanase was also inhibited by this peptide. The characteristics of this inhibition suggest that glycylglycine acts at the active site, does not function by metal binding and that minor alterations in the glycylglycine molecule preclude the inhibition. A specific inhibition of urocanases by glycylglycine has been observed. PMID- 2577700 TI - [Desensitization during play situation for children with negative behaviour in stomatological environment]. AB - A new form of desensitization during play situation for children, aged from to six, is applied. The method includes a fictitious treatment of the children with the participation of a figurative toy and a play-sketch. The children have shown fear reactions and negative behaviour in stomatological environment before the desensitization. The results from the study confirm the effectiveness of that form in influencing the fear and behaviour of the children in stomatological environment. PMID- 2577701 TI - Total parenteral nutrition as all in one. Clinical advantages and technical aspects. Symposium proceedings. Deauville, France, June 11-13, 1989. PMID- 2577702 TI - Intravenous labetalol for the treatment of hypertension after carotid endarterectomy. AB - Hypertension after carotid endarterectomy has a variable incidence ranging up to 56%. Blood pressure (BP) control is essential due to possible increased risk of morbidity from neurologic deficits or cardiovascular complications. This study evaluated intravenous labetalol for control of hypertension after carotid endarterectomy. Sixty ASA II-IV patients were studied; 20 developed BP high enough for treatment with labetalol. The anesthetic technique was standardized. Labetalol was administered at the conclusion of surgery as a 20-mg bolus over two minutes followed by 40 mg every 10 minutes until the desired BP was achieved (BP less than or equal to 10% above average preoperative BP or less than 150 mmHg, systolic) or 300 mg had been given. The mean total dose of labetalol was 42.0 +/- 33.0 mg (mean +/- SD) and mean time to reach the desired BP was 16.2 +/- 21.4 minutes. Systolic, diastolic, mean arterial pressure and heart rate significantly decreased after labetalol treatment and remained so for the remainder of the 180 minute study period. There was no hypotension, bradycardia, evidence of myocardial ischemia or central nervous system dysfunction present with labetalol treatment. Blood samples were obtained for determination of plasma renin activity, epinephrine, and norepinephrine in 10 patients who developed hypertension and received labetalol, and 10 patients who did not develop hypertension. In the patients developing hypertension, there was a significant elevation in epinephrine just before treatment, that decreased by 30 minutes after treatment. Norepinephrine levels became significantly elevated five minutes after labetalol treatment in the group with hypertension and remained elevated for 120 minutes. Concomitantly, there was a significantly lower plasma renin activity seen in this group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2577703 TI - Hemodynamic effects of dopexamine in patients following coronary artery bypass surgery. AB - Dopexamine is a new dopamine analogue, with combined agonist properties on dopamine receptors and the beta 2-adrenoceptor. The aim of this study was to evaluate the short-term hemodynamic effects of dopexamine at different dosage rates in postoperative coronary artery bypass (CABG) patients, especially with respect to the right ventricle, using a right ventricular ejection fraction pulmonary artery catheter. With a dose of 2 micrograms/kg/min of dopexamine, significant increases in heart rate (25%), cardiac index (33%), and right ventricular ejection fraction (20%) were observed. Pulmonary vascular resistance decreased with a dose over 1 microgram/kg/min (15%). Mean arterial blood pressure and pulmonary artery pressures were not affected. At 4 micrograms/kg/min, cardiac index was further increased. In conclusion, dopexamine could be beneficial to patients with a compromised right ventricle by lowering afterload and improving ventricular performance after CABG. PMID- 2577704 TI - Case conference 4--1989. A 4-year-old, 17-kg boy with panhypopituitarism, cryptorchidism, developmental delay, and second-degree heart block. PMID- 2577705 TI - Esmolol in tetralogy of Fallot. PMID- 2577707 TI - Peripheral vascular effects of dopexamine hydrochloride during cardiopulmonary bypass. PMID- 2577706 TI - Prolonged infusion of varied doses of dopexamine hydrochloride for circulatory failure after cardiac surgery. PMID- 2577708 TI - Hemodynamic effects of dopexamine hydrochloride administered by an intracoronary infusion technique. PMID- 2577709 TI - The use of dopexamine hydrochloride in patients with low cardiac output after cardiac surgery. PMID- 2577710 TI - Tubular enzymuria in cardiac surgery and bypass. Comparison with general surgery. PMID- 2577712 TI - Cardiovascular collapse and refractory bronchospasm following administration of vancomycin, esmolol, and heparin. PMID- 2577711 TI - Diltiazem withdrawal before coronary artery bypass surgery. AB - The authors studied the effects of withdrawing oral diltiazem therapy on the subsequent course of coronary artery bypass graft surgery. Patients with severe coronary artery disease were divided into three groups using a prospective, controlled, randomized protocol. In group D (diltiazem-continuation) patients, diltiazem was administered 2.1 +/- 0.1 hours (mean +/- SEM) before anesthetic induction (n = 10). Group DW (diltiazem-withdrawal) patients received their final diltiazem dose 17.3 +/- 2.9 hours before anesthesia (n = 10). Group R was a reference group of patients not receiving diltiazem (n = 11; not randomized). Anesthesia was induced and maintained with fentanyl and pancuronium without use of halogenated anesthetics. No clinically important differences were detected in measured hemodynamics or drug requirements. Group D patients did not have a lower systemic vascular resistance (SVR) index (P greater than 0.31) or mean arterial pressure (P greater than 0.08) compared with group DW. Also, no evidence for a diltiazem withdrawal response was found, because group DW did not have either a higher SVR index (P = 0.99) or a higher pulmonary vascular resistance index (P = 0.99) compared with group R, and no severe myocardial ischemia, coronary artery spasm, or postoperative heart block were seen. Plasma diltiazem concentrations decreased significantly during CPB (P less than 0.0001), but showed overlap between groups D and DW. Plasma diltiazem concentration did not correlate significantly with simultaneous SVR. These data show the benign effects of both diltiazem administration and its acute withdrawal before coronary artery bypass surgery with high-dose fentanyl anesthesia. PMID- 2577713 TI - Multivariate analysis of monoamine indices in patients with chronic schizophrenia. AB - Levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid and serum levels of prolactin (PRL) and dopamine-beta-hydroxylase (DBH) were measured in 42 chronic schizophrenic inpatients grouped according to their scores on the Brief Psychiatric Rating Scale (BPRS) and the Abnormal Involuntary Movement Scale (AIMS). Factor analysis was carried out on various combinations of variables. In patients with tardive dyskinesia (TD), cerebrospinal fluid DA, DOPAC, HVA, NA, and serum DBH were distributed into three factors; in patients without TD, these substances were assembled in only one factor. Cerebrospinal fluid DA, DOPAC, and HVA were dispersed in two factors in patients with severe positive symptoms versus one factor in subjects with mild productive signs. Factor structures diverged only when the variables listed above were included in the analysis. These findings support the hypothesis that both the dopaminergic and the noradrenergic system contribute to TD and that positive schizophrenic symptoms are associated with dopaminergic dysregulation. PMID- 2577715 TI - Proceedings of the XIVth Congress of the International Academy of Legal Medicine and Social Medicine. Liege, Belgium, 11-17 September 1988. PMID- 2577714 TI - Successful use of clozapine in a patient with a history of neuroleptic malignant syndrome. AB - Reinstitution of antipsychotic medication is problematic in patients with a history of neuroleptic malignant syndrome (NMS). In this case, a patient with a history of probable neuroleptic malignant syndrome caused by administration, as single agents, of haloperidol, molindone, and lithium was later treated successfully with the novel antipsychotic clozapine. The propensity of various antipsychotic agents to cause NMS is discussed. PMID- 2577717 TI - Simultaneous HPLC determination of floctafenine and its main metabolites. PMID- 2577716 TI - Exclusion of paternity by DNA analysis in addition to blood group testing in a family case. AB - Three men, all related to the mother were involved in a paternity case. Only one of them, an uncle of the mother, could be excluded by conventional blood testing of 22 polymorphic systems including HLA and Gm. Because it was not possible to exclude the other men (the brother and the father of the mother) by these systems restriction fragment length polymorphisms as detected by the probes YNH24 and hMF1 were analyzed. The results with probe hMF1 did not reveal additional information. Both Taq I and Pst I digests, probed with YNH24 excluded the father of the mother from paternity of the child under investigation. PMID- 2577718 TI - Neurotensin-like immunoreactivity in cerebrospinal fluid of patients with schizophrenia, depression, anorexia nervosa-bulimia, and premenstrual syndrome. AB - Neurotensin (NT) concentrations in cerebrospinal fluid (CSF) were measured by a sensitive and specific radioimmunoassay in psychiatric patients and age- and sex matched normal controls. No increase in CSF NT concentrations was observed after antipsychotic drug treatment. CSF NT concentrations were significantly lower in one group of schizophrenic subjects. NT concentrations were unaltered in patients with depression, anorexia/bulimia, or premenstrual syndrome, and no rostral caudal gradient for NT in CSF was evident. NT concentrations were not related to age or sex, and probenecid treatment did not alter CSF NT concentrations. Finally CSF NT concentrations were unaltered in paranoid schizophrenic subjects. These findings confirm and extend previous studies of CSF NT that showed certain patients with schizophrenia, nonparanoid type, have reduced CSF concentrations of this tridecapeptide. PMID- 2577719 TI - Psychiatric presentations of intracranial cysts. AB - Eight patients with intracranial cysts presenting with primary psychiatric diagnoses were studied. The cysts were visible on computed tomography (CT) and magnetic resonance imaging (MRI), and they produced neurologic, electroencephalographic (EEG), and neuropsychologic abnormalities. Descriptions of psychiatric manifestations associated with intracranial cysts are rare, and their potential neuropsychiatric significance has been minimized. This study demonstrates that intracranial cysts can cause neuropsychiatric symptoms, that surgical intervention may resolve the psychiatric manifestations in selected cases, and, in cases not warranting surgery, that psychopharmacological therapy to treat the behavioral manifestations is indicated. These cases mandate consideration of intracranial cysts in the diagnostic and therapeutic formulation of atypical neuropsychiatric disorders. PMID- 2577721 TI - The combination of amantadine and neuroleptics plus time may cure tardive dyskinesia. PMID- 2577720 TI - Receptor mechanisms in antipsychotic drug action: focus on sigma receptors. AB - The principal antischizophrenic neuroleptic drugs in current clinical use act by blocking dopamine receptors, which mediate extrapyramidal side effects and tardive dyskinesia. As an alternative strategy, researchers have sought agents that do not influence dopamine receptors but whose behavioral effects in animals resemble those of neuroleptics. Some promising "new generation" candidate drugs have shown beneficial effects in schizophrenic patients in early clinical trials. These new agents share a selective, high affinity for sigma receptors, sites where psychotomimetic opiates act. A systematic screen for drugs that block sigma receptors may provide a valuable strategy in identifying novel antischizophrenic agents and in clarifying the pathophysiology of psychosis. PMID- 2577722 TI - Characterization of SSEA-1 glycolipids from the brain of a patient with fucosidosis. AB - Neutral glycolipids from the brain of a patient with Fucosidosis were analyzed and two complex glycolipids containing five and eight sugars were isolated from the cortical grey matter. These two glycolipids reacted with antibodies recognizing the SSEA-1 [Le(x)(X)] carbohydrate determinant. SSEA-1 glycolipids are normally expressed in human embryonic brain but are found in only small amounts in postnatal human brain. The accumulation of the two SSEA-1 glycolipids in Fucosidosis brain thus represents a defect which affects the normal developmentally regulated decrease in postnatal expression of these glycolipids, and may be a contributing factor in the abnormal brain development associated with the disease. Chemical characterization of the two isolated glycolipids by gas chromatographic and mass spectrometric analyses has identified the two glycolipids as lacto-N-fucopentaosylceramide (III) and difucosyl neolactonorhexaosylceramide. PMID- 2577723 TI - Molecular characterization of an aberrant allele for the Gy3 glycinin gene: a chromosomal rearrangement. AB - The soybean variety Forrest contains an aberrant allele for the Gy3 glycinin gene. The aberrant allele is designated gy3 because mRNA for the G3 glycinin subunit is reduced to below detectable amounts in the seed. Molecular and genetic characterization of gy3 show it to be associated with a chromosomal rearrangement that causes the 5' halves and 3' halves of the gene to become separated from one another in the genome. An inversion is the simplest structural model that accounts for the genetic and molecular features of the chromosomal rearrangement involving gy3, although more complex models that involve reciprocal translocations are also consistent with the data. PMID- 2577724 TI - Several proteins imported into chloroplasts form stable complexes with the GroEL related chloroplast molecular chaperone. AB - Nine different proteins were imported into isolated pea chloroplasts in vitro. For seven of these [the large and small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), beta-subunit of ATP synthase, glutamine synthetase, the light-harvesting chlorophyll a/b binding protein, chloramphenicol acetyltransferase, and pre-beta-lactamase], a fraction was found to migrate as a stable high-molecular-weight complex during nondenaturing gel electrophoresis. This complex contained the mature forms of the imported proteins and the groEL related chloroplast chaperonin 60 (previously known as Rubisco subunit binding protein). Thus, the stable association of imported proteins with this molecular chaperone is widespread and not necessarily restricted to Rubisco subunits or to chloroplast proteins. With two of the imported proteins (ferredoxin and superoxide dismutase), such complexes were not observed. It seems likely that, in addition to its proposed role in assembly of Rubisco, the chloroplast chaperonin 60 is involved in the assembly or folding of a wide range of proteins in chloroplasts. PMID- 2577725 TI - Photorespiration and light act in concert to regulate the expression of the nuclear gene for chloroplast glutamine synthetase. AB - In Pisum sativum, distinct chloroplast and cytosolic forms of glutamine synthetase (GS) are encoded by homologous nuclear genes that are differentially expressed in vivo (Tingey, S. V., Tsai, F.-Y., Edwards, J. W., Walker, E. L., and Coruzzi, G. M. [1988]. J. Biol. Chem. 263, 9651-9657). In leaves, light selectively affects the expression of the nuclear gene for chloroplast GS2. Differences in the maximal levels of GS2 mRNA in etiolated plants treated with red or white light indicate that only part of the white-light-induced accumulation of GS2 mRNA is due to a phytochrome-mediated response. The kinetics of GS2 mRNA accumulation in response to white-light illumination of etiolated or dark-adapted green plants indicates that GS2 mRNA accumulates more rapidly in plants containing mature, photosynthetically competent chloroplasts. Other evidence that GS2 mRNA levels are affected by the metabolic status of chloroplasts concerns the selective induction of GS2 mRNA in plants grown under conditions that result in the production of photorespiratory ammonia. These results indicate that the light-induced accumulation of GS2 mRNA in leaves results from the action of phytochrome as well as light-induced changes in chloroplast metabolism. PMID- 2577728 TI - Engrailed gene expression in the abdominal segment of Oncopeltus: gradients and cell states in the insect segment. AB - A monoclonal antibody that recognizes the product of the segmental gene, engrailed (en), of Drosophila has been used to analyse expression of the homologous gene of Oncopeltus. engrailed expression in the abdominal segment of larval Oncopeltus is confined to a narrow band of epidermal cells localized immediately anterior to the segment border. Expression varies in intensity during postembryonic development: no gene product is detectable in newly moulted larvae, but reappears soon after initiation of intermoult activities. One possible function of en in this system is revealed by a series of operations confronting cells from different anteroposterior levels in the segment. New segment borders are generated only when en-expressing cells confront cells from the anteriormost region of the segment. All other combinations result in intercalation of intermediate intrasegmental levels. It is therefore suggested that the most important function of en is the establishment of new, and presumably the maintenance of existing, segment borders. PMID- 2577726 TI - Rubisco assembly: a model system for studying the mechanism of chaperonin action. PMID- 2577727 TI - Two glutamine synthetase genes from Phaseolus vulgaris L. display contrasting developmental and spatial patterns of expression in transgenic Lotus corniculatus plants. AB - The gln-gamma gene, which specifies the gamma subunit of glutamine synthetase in Phaseolus vulgaris L., has been isolated and the regulatory properties of its promoter region analyzed in transgenic Lotus corniculatus plants. A 2-kilobase fragment from the 5'-flanking region of gln-gamma conferred a strongly nodule enhanced pattern of expression on the beta-glucuronidase reporter gene. Parallel studies on the promoter of another glutamine synthetase gene (gln-beta) showed that a 1.7-kilobase fragment directed 20-fold to 140-fold higher levels of beta glucuronidase expression in roots than in shoots. Histochemical localization of beta-glucuronidase activity in nodules of the transgenic plants indicated that the chimeric gln-gamma gene was expressed specifically in the rhizobially infected cells; expression of the gln-beta construct was detected in both cortical and infected regions of young nodules, and became restricted to the vascular tissue as the nodule matured. We conclude that gln-beta and gln-gamma genes are differentially expressed both temporally and spatially in plant development and that the cis-acting regulatory elements responsible for conferring these contrasting expression patterns are located within a 2-kilobase region upstream of their coding sequences. PMID- 2577729 TI - Role of Escherichia coli type 1 pilus in colonization of porcine ileum and its protective nature as a vaccine antigen in controlling colibacillosis. AB - This study was designed to evaluate the role of Escherichia coli type 1 pili in adherence of the organism to porcine small intestines and the efficacy of pili as a vaccine antigen in controlling neonatal colibacillosis. Our results demonstrated that an E. coli phase cloned to express type 1 pili readily attached to the small intestines of colostrum-deprived newborn pigs. Immunofluorescent staining of intestine sections revealed the presence of E. coli expressing type 1 pili only on the brush border, suggesting involvement of type 1 pili in the colonization process. Administration of anti-type 1 serum to newborn pigs prior to challenge reduced the level of gut-associated E. coli sixfold compared with controls. Purified type 1 pilus vaccine induced significant protection against colibacillosis in newborn pigs following challenge with E. coli expressing type 1 pili. Pigs born to vaccinated gilts scoured less and gained more weight than pigs born to control gilts. Our results demonstrate that type 1 pili are a virulence factor, as well as an effective vaccine antigen. PMID- 2577731 TI - Physicochemical properties of bacterial surfaces. PMID- 2577730 TI - Amino acid sequences of pilins from serologically distinct strains of Bacteroides nodosus. AB - Amino acid sequences of pilin from a strain of Bacteroides nodosus from serogroup B (234) and serogroup C (217) were determined. The amino-terminal N methylphenlalanine residue of both proteins was followed by a hydrophobic sequence of 30 residues closely related to the N-terminal sequence of other pili having an amino-terminal residue of N-methylphenylalanine. These data lend support to the hypothesis that in pilins of this type, the amino-terminal sequence functions as a transport signal necessary for pilin to reach its external environment, as well as promoting intersubunit interactions for maintenance of the structural integrity of the pilus. Two hydrophilic hypervariable regions can be discerned across the pilin sequences, indicating possible locations of antigenic domains. PMID- 2577732 TI - When do metal complexes protect the biological system from superoxide toxicity and when do they enhance it? AB - Many copper and iron complexes can be reduced by O2- as well as by H2O2. According to the rates of reduction and the concentration of O2- and H2O2, the metal complexes may serve either as catalyst of O2- dismutation or as catalysts of the reaction between O2- and H2O2 to form OH. radical (Haber-Weiss reaction). Various factors which influence whether metal complexes protect the biological systems from superoxide toxicity or enhance it are discussed. PMID- 2577734 TI - Aspects to consider when detecting and measuring lipid peroxidation. PMID- 2577733 TI - Hydroxyl free radical adduct of deoxyguanosine: sensitive detection and mechanisms of formation. AB - DNA or 2-deoxyguanosine reacts with hydroxyl free radical to form 8-hydroxy deoxyguanosine (8-OH-dG). We found that 8-OH-dG can be effectively separated from deoxyguanosine by high pressure liquid chromatography and very sensitively detected using electrochemical detection. The sensitivity of electrochemical detection is about one-thousand fold enhanced over optical detection. Utilizing deoxyguanosine in bicarbonate buffer it was found that ferrous ion, but not ferric ion, was effective in forming 8-OH-dG. The hydroxyl free radical scavenging agents, thiourea and ethanol, were very effective in quenching Fe(11) mediated 8-OH-dG formation, but superoxide dismutase had very little effect. PMID- 2577735 TI - Pro-oxidant action of superoxide dismutase in the autoxidation of rifamycin SV. PMID- 2577736 TI - Comparison of pharmacokinetic and cell binding properties of turkey Cu-SOD and E. coli Mn-SOD. AB - The pharmacokinetics in rats and cell fixation properties of coli Mn-SOD are compared with those of Cu-SODs extracted from turkey blood. Despite similarities in molecular weight and pl the different enzymes show different characteristics. The results are discussed with respect to the mechanism of anti-inflammatory activity of superoxide dismutase. PMID- 2577738 TI - The effect of vitamin E-deficiency in isolated rat heart on the cellular defence system against free radicals during normal reperfusion after hypoxic, ischemic and Ca(2+)-free perfusion. AB - We investigated whether vitamin E plays a role in the protection against potential free radical formation and related biochemical changes in hypoxic, ischemic and Ca(2+)-depleted rat heart upon normal reperfusion. In the heart of normally fed rats a decrease in the activity of superoxide dismutase and the capacity of the glutathione system, factors of the cellular protective mechanisms against free radicals, occurred upon exposure to the above mentioned treatments. This decrease was not further enhanced if vitamin E-deficient rat hearts were treated. Vitamin E-deficiency, however, led to detectable peroxidation of lipids if Ca(2+)-depleted or hypoxic hearts were reperfused. Lipid peroxidation was measured as the formation of thiobarbituric acid reactive material, which is readily formed during this process. Reflow after ischemia did not induce lipid peroxidation either in normal or in vitamin E-deficient rat heart. Since changes in Ca(2+)-homeostasis are thought to be primarily responsible for the Ca(2+) reperfusion injury, a role for Ca(2+)-ions in lipid peroxidative processes, either directly or indirectly, seems indicated. Furthermore the results imply that even a sharp and extensive decrease of reduced glutathione, as seen upon Ca(2+)-repletion after a period of Ca(2+)-depletion, does not necessarily induce peroxidation of lipids in heart tissue. Obviously, vitamin E is very important in the protection of cardiac membranes. Replenishment of the water-soluble protective factors in the heart seems, however, more important during above mentioned treatments, especially since repair of the vitamin E-free radical is dependent on water-soluble factors. PMID- 2577737 TI - The role of plasma in oxidative haemolysis. PMID- 2577739 TI - [Unilateral vertical posterior insufficiency syndrome of the face. Clinical and therapeutic aspects]. PMID- 2577741 TI - [Temporomandibular joint injuries. Disability evaluation according to quantitative and qualitative aspects]. AB - Presently the calculation of the grade of invalidity of the temporomandibular joint due to trauma, according to Belgian law, poses a number of problems concerning applicability and differentiation. This article proposes a reviewed version of article 27 based on recent representative literature. PMID- 2577742 TI - [Facial malformations and asymmetries due to first and second branchial arch syndromes]. AB - The first and second branchial arch syndrome is a congenital affection, among whom one can range as well hereditary as non-hereditary entities. They always cause a badly mutilating facial asymmetry. In this article, the first and second branchial arch syndrome were divided in hemifacial and bilateral dysostoses. We pointed out the hemifacial microsomia, the most occurring entity in these series. From two case reports, we attempt to give a treatment synopsis of this syndrome, which is always done by a multi-disciplinary team, including dentists, orthodontists, maxillofacial surgeons and plastic surgeons. PMID- 2577743 TI - [Reproducibility of the lip position at rest and when laughing]. PMID- 2577745 TI - [General review of maxillofacial mycoses]. AB - It is interesting and useful to review the different mycoses which can affect oral and maxillofacial tissues. In this review, all mycoses which can involve these tissues are described, based on a simple classification into superficial and deep mycoses. The superficial mycoses described are the dermatophytoses, the Tineas, the piedras, but also the candidoses, which are superficial opportunistic infections. The deep mycoses are subdivided into subcutaneous, systemic, and opportunistic mycoses. Subcutaneous fungal infections are sporotrichosis, lobomycosis, rhinosporidiosis, entomophtoromycoses, and chromomycoses. Systemic fungal infections are paracoccidioidomycosis, blastomycosis, cryptococcosis, histoplasmosis, histoplasmosis duboisii, and coccidioidomycosis. Opportunistic mycoses are aspergillosis, mucormycosis, geotrichosis, torulopsosis (considered nowadays as a candidosis), basidiomycosis, cephalosporiomycosis, alternariosis, cercosporomycosis, paecilomycosis, and fusariomycosis. Eumycotic mycetomas are also cited. PMID- 2577746 TI - [Are Ag-points, gutta percha and amalgam still applicable for apical sealing?]. AB - Nowadays Ag-points, gutta percha and amalgam are widely used as orthograde or retrograde root-filling materials. The biocompatibility of these materials however remains debatable. Ag-points are easy to manipulate and when used together with an appropriate cement, offer an adequate seal. Yet an important disadvantage is the susceptibility to corrosion resulting in argyrosis and inflammatory reaction. Tissue cultures proved these corrosion by products to be highly cytotoxic. Other investigations, reported that the inflammatory tissue response seen with gutta percha, may be due to small amounts of additives included in gutta percha. Equally, there is no unanimity concerning the biocompatibility of amalgam, and the extent of corrosion and inflammatory reaction is possibly related to the composition of the amalgam used. Nevertheless in vivo studies demonstrated that, when freshly mixed amalgam, gutta percha or Ag points are implanted in the femur of rats, mature bone was formed in direct contact with these materials. PMID- 2577748 TI - [Comparative study between pirprofen (Rengasil) and piritramid (Dipidolor) for postoperative pain in maxillofacial surgery]. AB - In this clinical single-blind trial, the potential analgesic effect of pirprofen (Rengasil) was compared to the analgesic effect of piritramide (Dipidolor). The two compounds were tested intramuscularly in patients submitted to maxillofacial surgery. Pirprofen and piritramide seem to have an equivalent analgesic effect but pirprofen (Rengasil) seems to act a little faster and to be better tolerated than piritramide. Therefore, pirprofen may be utilized with success to treat postoperative pain in patients who undergo maxillofacial surgery: its advantage is avoiding secondary effects of the morphinomimetic compounds. PMID- 2577747 TI - [Fine-needle puncture of salivary gland tumors]. AB - Fine needle aspiration cytology of major salivary glands is easy to perform at a low cost. Its predictive value is 100% for malignancy. Its main indications are: the diagnosis of inflammatory lesions, of malignant growths (either epithelial or lymphoma or metastases) and the follow-up of benign lesions which are not immediately amenable to surgery. PMID- 2577749 TI - [2 infrequent tumors of the mandible. Removal and reconstruction]. AB - Odontogenic myxoma and particularly juvenile fibromatosis are rare benign tumors in the maxillo-facial region. The aggressive local and sometimes voluminous development of these tumors may necessitate partial mandibulectomy. Autologous bone graft from the iliac crest is the best material for mandibular reconstruction because of its functional and esthetic results. If osteosynthesis of the graft is achieved by means of internal wiring, several weeks of intermaxillary fixation are required, whereas internal rigid fixation with plate and screws allows the patient to open the mouth more rapidly. PMID- 2577750 TI - [Interventional procedures in the region of the external carotid artery]. PMID- 2577751 TI - [Biocompatible materials for use in apicotomy]. AB - The use of more biocompatible materials in comparison with silver, gutta-percha and amalgam was introduced a decade ago. First titanium was used, later followed by alumina. Both clinical as well as radiological results favor their use. Yet it appears that the system is mainly confined to the maxillary front teeth and mandibular canines. PMID- 2577752 TI - 16th Bethesda Conference: Cardiovascular abnormalities in the athlete: recommendations regarding eligibility for competition. October 3-5, 1984. PMID- 2577753 TI - [Allergological assessment]. PMID- 2577754 TI - [Bronchial reactivity tests]. PMID- 2577756 TI - [Evaluation of alveolo-capillary exchange, using the method of global ductance of O2 and CO2, in early, preradiologic,diagnosis of pulmonary asbestosis]. PMID- 2577755 TI - [Radioisotopic study of the permeability of the alveolo-capillary barrier in man]. PMID- 2577757 TI - [Bronchoscopic assessments]. PMID- 2577759 TI - [The pulmonary surfactant system]. PMID- 2577758 TI - [Physico-chemical and biologic characteristics of bronchial secretions]. PMID- 2577760 TI - [Ciliary movement and radioisotopic parameters of the mucociliary function in respiratory pathology]. PMID- 2577761 TI - [The bronchiolo-alveolar microenvironment]. PMID- 2577762 TI - [Alveolar clearance dysfunction caused by air pollutants (study with DTPA Tc99m)]. PMID- 2577763 TI - [Bronchial hypersecretion]. PMID- 2577764 TI - [Bronchial reactivity]. PMID- 2577765 TI - [Methods for the study of reversible bronchial obstruction]. PMID- 2577767 TI - [Methods for the study of respiratory injury caused by the environment to assess the pathologic components present in the respiratory system]. PMID- 2577766 TI - [Bronchopulmonary infective components]. PMID- 2577768 TI - [Non-biologic microparticulate air pollutants]. PMID- 2577769 TI - ["Allergic or immunologic" bronchopathies, pneumopathies, bronchopneumopathies]. PMID- 2577770 TI - [Occupational bronchopathies, pneumopathies, bronchopneumopathies]. PMID- 2577771 TI - [Main non-specific respiratory tract infections associated with the environment]. PMID- 2577772 TI - [Pulmonary tuberculosis in contaminated environments]. PMID- 2577773 TI - [Natural course of chronic bronchitis as a disease determined by environmental risk factors]. PMID- 2577774 TI - [Infective superinvasions as the cause of chronic bronchitis progression]. PMID- 2577775 TI - [Pulmonary emphysema: morphogenesis and pathogenesis of the lesion]. PMID- 2577776 TI - [Emphysema and pulmonary dystrophy: morphologic and hemodynamic profiles of the pulmonary circulation]. PMID- 2577777 TI - [Interstitial disease and pulmonary fibrosis]. PMID- 2577779 TI - ["Prevention of bronchopneumopathy in childhood"]. PMID- 2577778 TI - [Possible factors of early sensitization in infant allergic asthma]. PMID- 2577780 TI - [Pulmonary tumors and the environment]. PMID- 2577781 TI - [Air-dispersed dust of environmental origin as carcinogenic risk factor]. PMID- 2577782 TI - [The role of occupational exposure in the etiology of pulmonary tumors]. PMID- 2577783 TI - [Tobacco use and health: a preventable epidemics]. PMID- 2577784 TI - [Pulmonary metabolic activity in relation to carcinogenic substance exposure]. PMID- 2577785 TI - [Correlation between chronic bronchopneumopathy and carcinoma of the lung]. PMID- 2577786 TI - [Biological prognostic factors in the natural history of bronchopulmonary tumors]. PMID- 2577787 TI - [Biological tumor markers]. PMID- 2577788 TI - [Secondary prevention of pulmonary carcinoma]. PMID- 2577789 TI - [Diagnosis, staging and follow-up of pulmonary carcinoma: current aspects]. PMID- 2577790 TI - [Usefulness of the administration of retinol palmitate to patients operated on for non-small-cell lung carcinoma in first 'A' stage]. PMID- 2577791 TI - [Situation and choice of antimicrobial agents with effects on the so-called "non specific" respiratory infections]. PMID- 2577792 TI - [Current approaches in antitubercular therapy]. PMID- 2577793 TI - [Treatment of infective recurrences of chronic bronchopneumopathies with Klebsiella pneumoniae extracts]. PMID- 2577794 TI - [Immunodeficiency syndrome: "thymopentin"]. PMID- 2577795 TI - [Cancer of the lung. New perspectives in medical treatment]. PMID- 2577796 TI - [Mucolytic agents. Polycentric study of a carbocysteine-sobrerol combination]. PMID- 2577797 TI - [Ambroxol in the prevention of chronic bronchitis reactivation]. PMID- 2577798 TI - [Sobrerol and chronic bronchitis]. PMID- 2577800 TI - [Models of therapy for extrinsic allergic alveolitis]. PMID- 2577799 TI - [Acetylcysteine: up-date and perspectives of its future use]. PMID- 2577801 TI - [Bronchial dysreactive syndromes: bamifylline]. PMID- 2577802 TI - [Effect of procaterol in dosed aerosol and the procaterol-theophylline combination]. PMID- 2577803 TI - [Disodium cromoglycate in the prevention of bronchial hyperreactivity in the allergic asthmatic]. PMID- 2577804 TI - ["Anti-allergic" therapy for acute bronchial obstruction with a new glucocorticoid having an improved risk/benefit index]. PMID- 2577805 TI - [The use of nimesulide in respiratory disease]. PMID- 2577806 TI - [Restrictive broncho-obstructive dysventilatory syndromes]. PMID- 2577807 TI - [Hypoxic and hypoxemic-hypercapnic syndromes in respiratory diseases caused by the environment]. PMID- 2577808 TI - ["Pulmonary cardiopathy"]. PMID- 2577809 TI - [The suitable timing for prevention]. PMID- 2577810 TI - [Organization of the rehabilitative intervention]. PMID- 2577811 TI - [Airway clearance]. PMID- 2577812 TI - [Possibility of application of biofeedback in respiratory rehabilitation]. PMID- 2577813 TI - [Physical exercise retraining]. PMID- 2577814 TI - [Oxygen and ventilation therapy in long-term domiciliary care]. PMID- 2577815 TI - [Disability related to environmental respiratory disease: medico-legal problems]. PMID- 2577816 TI - [Health program for an effective primary prevention of carcinoma of the lung]. PMID- 2577817 TI - [Operative structure, policy and organization in pulmonary diseases of social interest in the national health system]. PMID- 2577818 TI - [Radiologic and radioisotopic assessment in the study of environmental respiratory disease]. PMID- 2577819 TI - [Assessment of respiratory function in the evaluation of disabling respiratory lesion]. PMID- 2577820 TI - [Blood gas analysis and oxygen transport. Notes on measured, estimated and special parameters]. PMID- 2577821 TI - [Cardiohemodynamic pulmonary assessment in environmental respiratory disease]. PMID- 2577823 TI - Where do we go from here? PMID- 2577822 TI - Physician contribution to indigent care. The experience of Volusia County. PMID- 2577824 TI - A hospice Christmas. PMID- 2577825 TI - The need to reform indigent care. PMID- 2577826 TI - Questions on chelation therapy. PMID- 2577827 TI - More tales about chelation therapy. PMID- 2577828 TI - Are two dead doctors enough? PMID- 2577829 TI - More Medicare woes. PMID- 2577830 TI - Postmortem often still needed. PMID- 2577831 TI - Stable isotope ratio analysis of leucine and ketoisocaproic acid in blood plasma by gas chromatography/mass spectrometry. Use of tertiary butyldimethylsilyl derivatives. PMID- 2577832 TI - Mass spectrometry of 3,4-dihydroquinazol-4-ones of pharmaceutical interest. Part 2: Common structure of the C8H4N2R+ ions from 3-isoxazolyl-3-pyrazolyl-, and 3-o tolyl-2-R-substituted derivatives. PMID- 2577833 TI - Effects of sample matrix and high performance liquid chromatography eluent composition on the thermospray response for polar compounds. PMID- 2577834 TI - Neopentane as a possible replacement for isobutane in chemical ionization mass spectrometry. PMID- 2577835 TI - A continuous-flow probe high performance liquid chromatography interface to a liquid secondary-ion time-of-flight mass spectrometer. PMID- 2577836 TI - The determination of protein, oligonucleotide and peptide molecular weights by ion-spray mass spectrometry. AB - The mass spectra of several compounds with molecular weights in the 2500-20,000 Da range were obtained with a quadrupole mass spectrometer equipped with an atmospheric pressure ion source. Average molecular weight determinations of mellitin (2846.4 Da), a synthetic oligonucleotide (4262.8 Da), myoglobin (16,950.4 Da) and on the subunits of beta-lactoglobulin (18,277.1 Da) requiring as little as 1 pmol of material were achieved with accuracies and precisions of +/- 1 Da. An ion-spray interface was used to produce ions via the ion evaporation process, producing mass spectra containing a series of multiply-charged molecular species. A simple method for calculating the molecular weight of unknown compounds from the spectra containing multiply-charged ions is described. PMID- 2577837 TI - Reversible reductions of oxazine dyes induced by primary particle bombardment in liquid secondary-ion mass spectrometry. PMID- 2577838 TI - A convenient route to stable-isotope-labelled compounds for use in quantitative gas chromatography/mass spectrometry. PMID- 2577839 TI - Application of continuous-flow liquid chromatography/fast-atom bombardment mass spectrometry to the analysis of diagnostic acylcarnitines in human urine. AB - Acylcarnitine profiles of diagnostic value were generated from the equivalent of 0.1 microL of raw urine using the continuous-flow liquid chromatography/fast-atom bombardment mass spectrometry (LC/FAB-MS) interface for sample introduction. Further analysis was accomplished by gradient LC/MS using a commercially available packed fused-silica microbore column. PMID- 2577840 TI - Thermospray mass spectrometry of thiazides. A novel elimination and rearrangement resulting from a molecular adduct ion. PMID- 2577841 TI - Evidence for competitive intramolecular trimethylsilyl rearrangement to oxygen and sulfur in beta-trimethylsilylethylthiolesters. PMID- 2577842 TI - Atmospheric pressure chemical ionization and electrospray mass spectrometry of some organoarsenic species. PMID- 2577843 TI - Plasma desorption mass spectrometric analysis of glycosylated ovomucoid third domain from Japanese quail. PMID- 2577844 TI - Fast atom bombardment/collisional activation mass spectrometry of beta-D-mannosyl (1----4)-beta-D-N-acetylglucosaminyl (1----N) urea and related compounds. AB - A new compound, obtained during the isolation of oligosaccharides from the urine of two brothers affected with inherited beta-mannosidase deficiency, has been investigated using fast atom bombardment ionization and MS/MS techniques. The compound could be characterized as an N-acetylglucosamine molecule linked to a hexose and a urea molecule. PMID- 2577845 TI - Tandem mass spectrometry of prostaglandins: a comparison of an ion trap and a reversed geometry sector instrument. PMID- 2577846 TI - Fast atom bombardment and plasma desorption mass spectrometry of degraded insulins in intermediate and long-acting preparations. PMID- 2577847 TI - Cytidylate cyclase activity: identification of cytidine 3',5'-cyclic monophosphate and four novel cytidine cyclic phosphates as biosynthetic products from cytidine triphosphate. AB - Identification of cytidine 3',5'-cyclic monophosphate (cyclic CMP) as one of the products resulting from the incubation of dialysed cell-free preparations from rat brain, liver and kidney with cytidine 5'-triphosphate (CTP) is described. The non-acidic precipitable products after incubation of the tissue preparations with unlabelled, with 14C-single labelled, and with 14C- and 32P-dual labelled CTP were examined by thin-layer chromatography and high-pressure liquid chromatography, isotopic ratio determination, UV absorbance spectrophotometry, selective hydrolysis with nucleotidase, phosphodiesterase and acid, and by fast atom bombardment mass spectrometry with mass-analysed ion kinetic energy spectrum scanning. In addition to cyclic CMP and unchanged CTP, the products of the reaction were found to include cytidine monophosphate (CMP) and cytidine diphosphate (CDP) together with four novel cytidine compounds identified as cytidine 3',5'-cyclic pyrophosphate, cytidine 2'-monophosphate 3',5'-cyclic monophosphate, cytidine 2'-O-aspartyl-3',5'-cyclic monophosphate and cytidine 2' O-glutamyl-3',5'-cyclic monophosphate. The evidence presented constitutes conclusive proof of the natural occurrence of cytidylate cyclase activity; the four novel cytidine cyclic phosphates described provide a feasible explanation of the discrepancies in previous reports which have led to the controversy which exists concerning the existence of cytidylate cyclase activity. PMID- 2577848 TI - Collisionally activated decomposition of leucine-enkephalin and analogues using a hybrid tandem mass spectrometer. PMID- 2577849 TI - Competition between protein/protein interactions and protein/substrate interactions studied by plasma desorption mass spectrometry. PMID- 2577850 TI - A pulsed time-of-flight mass spectrometer for liquid secondary ion mass spectrometry. AB - The design and performance of a new time-of-flight mass spectrometer is reported. The instrument combines the advantages of a pulsed drawout TOF analyzer with a liquid secondary ion source. Differences from commercially available pulsed TOF analyzers (Wiley/McLaren type) are discussed with regard to operation with ion desorption from a liquid matrix. PMID- 2577851 TI - Fractal aggregates. AB - In recent years it has been shown that the structures of a wide variety of colloidal aggregates can be described in terms of the concepts of fractal geometry. The purpose of this review is to discuss some of the evidence for fractal geometry in experimental systems and indicate how fractal geometry can be used to develop a better understanding of their aggregation kinetics and physical properties. At the present time much of our understanding of the structure and properties of fractal aggregates has come from computer simulations. Consequently, a major part of this paper is concerned with the role played by simple computer models in understanding the origins of fractal aggregates as well as their physical and chemical properties. The main emphasis is on models for colloidal aggregation but a brief description of a few other models for non equilibrium growth and aggregation processes which have been of particular interest during the past few years has been included. PMID- 2577852 TI - Biomembrane structure and dynamics viewed by fluorescence. PMID- 2577854 TI - Fluorescence polarization to evaluate the fluidity of natural and reconstituted membranes. PMID- 2577853 TI - Time-resolved fluorescence depolarization techniques in model membrane systems. Effect of sterols and unsaturations. PMID- 2577856 TI - Spectroscopic analysis of the structure of bacteriorhodopsin. PMID- 2577855 TI - Fluidity of thyroid plasma membranes. PMID- 2577857 TI - Structure and dynamics of the liver microsomal monoxygenase system. PMID- 2577858 TI - Fluorescence studies on prokaryotic membranes. PMID- 2577859 TI - The study of cytoskeletal protein interactions by fluorescence probe techniques. PMID- 2577860 TI - Fluorescent probes for the acetylcholine receptor surface environments. PMID- 2577861 TI - Structural basis and physiological control of membrane fluidity in normal and tumor cells. PMID- 2577862 TI - Fusion of enveloped viruses with biological membranes. Fluorescence dequenching studies. PMID- 2577863 TI - Dynamic structure of membranes and subcellular components revealed by optical anisotropy decay methods. PMID- 2577864 TI - Principles of frequency-domain fluorescence spectroscopy and applications to cell membranes. PMID- 2577866 TI - Identification of a transforming activity suppressing sequence in the c-raf oncogene. AB - Our previous study revealed that the rat c-raf was activated by a rearrangement leading to replacement of the amino-terminal half of the product. Therefore, we suggested that some sequences present in the amino-terminal half might prevent c raf from becoming an active oncogene. To examine this possibility, we constructed a series of deletion mutants of c-raf cDNA by the random linker insertion method. By transfection of NIH3T3 cells with these mutants, a region whose deletion resulted in activation of c-raf was identified. This region is located at amino acid residues 245 to 261, immediate upstream of the kinase domain of the c-raf product and is rich in serine and threonine residues. This region includes a sequence of six amino acids, RSTSTP, which is conserved in the products of normal raf gene families of various species. This sequence is the best candidate for suppressing transforming activity of c-raf. PMID- 2577865 TI - Multiple negative elements upstream of the murine c-myc gene share nuclear factor binding sites with SV40 and polyoma enhancers. AB - We previously identified a 716 bp DNA segment, 424 to 1140 bp 5' of the murine c myc gene, which exhibited the properties of a transcriptional 'dehancer' because it negated the effects of the SV40 enhancer (Remmers et al., 1986). Here, we show that this 716 bp 'dehancer region' is composed of multiple negative elements each of which functions at a distance of > 1 Kb to inhibit the SV40 enhancer. One of these negative elements displays lymphoid cell specificity. HeLa cell nuclear factor binding sites are found within these negative effector sequences. One of these binding sites is related to that of the Py EF-C transcription factor which recognizes a short dyad symmetry element within the polyoma enhancer. Interestingly, a dimer of the Py EF-C recognition sequence exhibited a strong 'dehancer effect' in the pSV2CAT expression vector. These negative elements may function by interfering with transcription factors required for SV40 enhancer activity. PMID- 2577868 TI - Mutational analysis of a phosphotransfer motif essential for v-fps tyrosine kinase activity. AB - The catalytic domains of protein-tyrosine kinases such as the P130gag-fps oncoprotein contain the sequence HRDLAARN, followed thirteen residues C-terminal by DFG (P130gag-fps residues 1041-1048 and 1061-1063). These residues define a structural motif conserved among eucaryotic protein kinases (-RD----N, DFG) and shared with several procaryotic 3'aminoglycoside phosphotransferases (H-D----N, D G). Functional analysis of mutant v-fps proteins employing bacterial and mammalian expression systems indicated that this motif is critical for P130gag fps kinase activity and oncogenicity. In particular, conservative substitutions of the two invariant aspartates (asp1043, asp1061) with glutamate or asparagine completely eliminated enzymatic activity, suggesting that these residues are essential for catalysis. In contrast, substitution of arg1042 with glutamate decreased but did not eliminate v-fps kinase activity in bacteria. The effects of these and other amino acid substitutions within the phosphotransfer motif and at the nearby autophosphorylation site (tyr1073) of P130gag-fps indicate that these conserved residues are intrinsically essential to the execution or regulation of catalytic activity, and suggest that tight spatial constraints operate within the active centre of the v-fps tyrosine kinase domain. PMID- 2577867 TI - The avian cellular homolog of the oncogene jun. AB - We have isolated chicken genomic and cDNA clones representing the jun oncogene of avian sarcoma virus 17 (ASV17). The genomic clone lacks intron sequences within its protein coding domain, contains a CAAT box, seven SP-1 consensus sequences and TATA box-like elements upstream and two poly(A) addition signals downstream of the coding domain. The cellular jun protein is 310 amino acids in length. Cellular and viral jun proteins differ by three nonconservative amino acid substitutions of which two are located in the DNA-binding domain, by a 27-amino acid deletion in the amino terminal third of the viral jun protein, by eleven cell-coded amino acids that link the cellular jun coding domain to the viral gag domain and by the partial gag sequences constituting the amino terminal of the viral gag-jun fusion protein. The availability of a cellular jun cDNA now allows the construction of reciprocal recombinants between the viral and the cellular gene which will define the structural features required for the oncogenicity of v jun. PMID- 2577869 TI - A study of ras gene mutations in colonic adenomas from familial polyposis coli patients. AB - Using an in vitro amplification step (polymerase chain reaction) followed by oligonucleotide dot blot analysis, DNA samples from 29 familial polyposis coli patients (75 polyp-derived and 26 'normal' colon samples with no epithelial atypia) were screened for the presence of K-, N-, and H-ras mutations. Only 5 polyps contained ras mutations (7%)--all in K-ras codon 12. In each case 'normal' colon DNA was available and found to be negative in this assay. We also report the detection of K-ras codon 12 mutations in a stably non-tumorigenic immortal adenoma-derived cell line, PC/AA, and in a tumorigenic colorectal carcinoma cell line, PC/JW. Both epithelial cell lines were derived from different FPC patients. An activated K-ras gene was also found in cell line S/AN, isolated from a sporadic villous adenoma. These results provide further evidence that there are common molecular events involved in sporadic and hereditary colorectal carcinogenesis and that K-ras mutations can precede the development of malignancy. To our knowledge PC/AA is the first reported example of a human cell line bearing a mutant ras gene that is not tumorigenic and shows that the presence of an activated ras gene even in an immortal human cell line is insufficient for malignancy. PMID- 2577870 TI - Chromosome localization and expression pattern of Lmyc and Bmyc in murine embryonal carcinoma cells. AB - Using Southern blot analysis of DNA from mouse-hamster somatic cell hybrids, we have mapped Lmyc and Bmyc, two members of the myc family of genes, to mouse chromosomes 4 and 2, respectively. Furthermore, we have compared the regulation of Lmyc and Bmyc expression under different growth conditions and during in vitro differentiation of the murine EC line F9 and considered the findings in relation to our previous studies on Nmyc and c-myc expression in the same line (Sejersen et al., 1987). Lmyc was down-regulated at an early stage of visceral endoderm differentiation, similarly to c-myc and Nmyc, while Bmyc was expressed at a constant low level at all stages. Lmyc, but not c-myc and Nmyc, was upregulated in terminally differentiated visceral endoderm cells. Inhibition of protein synthesis by cycloheximide for 4 h induced a 70% increase in Lmyc and 30% increase in Bmyc transcript levels, indicating that the expression of these genes is negatively regulated by a short-lived protein. Mitogenic stimulation with insulin and transferrin did not affect Lmyc and Bmyc mRNA levels. Lmyc transcripts have a half life of 30 min, whereas the Bmyc transcript is highly stable, with a half life of 6 h. The half-lives of the c-myc and Nmyc transcripts have been estimated previously as 40 and 130 min, respectively. PMID- 2577872 TI - Distribution of the c-myc oncoprotein in normal and neoplastic tissues of the rat colon. AB - A rat model of 5-azoxymethane induced colon cancer was studied in order to correlate histopathological changes and the differential distribution of the c myc protein. Weanling Fisher 344 rats were injected with three, one week apart, subcutaneous injections of 5-azoxymethane (AOM) (15 mg kg-1) and the animals were divided into low and high fat diet groups. Nine colon tumors, of varying degrees of malignancy, that developed in the AOM-treated rats, and sections of normal colonic mucosa were examined. A rabbit polyclonal anti-c-myc antibody produced nuclear staining at 1:100 dilution in cryostat frozen sections of the normal rat colonic mucosa and the colon tumors when prepared with a Cryostat Frozen Sectioning Aid (CFSA). The tissue localization of the c-myc antibody staining revealed: (1) in normal mucosa, nuclei of the basal portion of the mucosa; (2) in adenomatous polyps, nuclei at all levels of the mucosa; and (3) in a carcinoma in situ, intense staining of glandular epithelial cell nuclei at all levels within the tumor. This procedure may provide a sensitive method for detecting abnormal cells in the colonic epithelium that have an altered proliferative capacity. PMID- 2577871 TI - The T-ALL specific t(11;14)(p13;q11) translocation breakpoint cluster region is located near to the Wilms' tumour predisposition locus. AB - A breakpoint cluster region (T-ALLbcr) has been previously described on 11p13 for T-ALL carrying t(11;14)(p13;q11). One further T-ALL breakpoint is described bringing to 5 out of 6 such translocations which are found to break within a maximum of 6.7 kb on chromosome 11p13. Studies of somatic cell hybrids derived from t(11;14)(p13;q11) T-ALL placed the T-ALLbcr between the genes for catalase (CAT) and the beta-subunit of follicle stimulating hormone (FSHB). This suggested a link between the T-ALLbcr and the Wilms' tumour predisposition locus (WT) since constitutional 11p13 deletions predispose to Wilms' tumour. Utilising somatic cell hybrids from patients with Wilms' tumours and aniridia, we show that while the T-ALLbcr maps distal to the catalase gene at 11p13, it maps outside the shortest region of overlap of a series of 11p13 deletions associated with Wilms' Aniridia. The data suggest the order of genes at 11p13 to be: centromere-CAT-T ALLbcr-WT-aniridia-FSHB-telomere. Therefore, the T-ALLbcr must lie very close to but may be distinct from the Wilms' predisposition locus at 11p13. PMID- 2577873 TI - The FGF-related oncogenes hst and int.2, and the bcl.1 locus are contained within one megabase in band q13 of chromosome 11, while the fgf.5 oncogene maps to 4q21. AB - Prompted by the observed co-amplification at the DNA level of the int.2 and hst fibroblast growth factor-related oncogenes in some tumor cells, we have investigated the precise localization of these two loci known to reside in band q13 of chromosome 11. We demonstrate by pulsed field gel analysis that these two genes are separated by only 40 kb, locate three HTF islands in their neighbourhood, and show that the bcl.1 locus (translocation breakpoint in B-cell proliferative malignancies) is not more than 1050 kb away. We also show that the fgf.5 gene which belongs to the same family is not part of this cluster and is located in band q21 of chromosome 4. PMID- 2577874 TI - Activation of a mcf.2 oncogene by deletion of amino-terminal coding sequences. AB - The mcf.2 transforming sequence was previously identified by tumorigenicity-assay of the mammary carcinoma cell line MCF-7, molecularly cloned and localized to Xq27 by in situ hybridization. cDNA clones representing both the activated gene and the corresponding portion of its normal counterpart were isolated and their nucleotide sequence determined. Sequence analysis showed that the mcf.2 gene was activated by rearrangement and loss of 5' sequences and no other alteration. Comparison of the mcf.2 nucleotide sequence with the recently published dbl sequence (Eva, A., G. Vecchio, D. Rao, S. Tronick & S. Aaronson (1988) Proc. Natl. Acad. Sci. USA, 85, 2061-2065) revealed that mcf.2 and dbl represent two different activated versions of the same proto-oncogene. PMID- 2577875 TI - The induction of Friend erythroleukaemia differentiation is markedly affected by expression of a transfected c-myb cDNA. AB - A minigene containing a cDNA encoding the normal mouse p80c-myb protein under strong promoter control was used to transfect Friend erythroleukaemia cells. Expression of the transfected gene was found to result in elevated levels of p80c myb which were not subject to rapid down-modulation by inducers of Friend cell differentiation as was the product of the endogenous c-myb gene. Continued synthesis of p80c-myb was found to be associated with a marked decrease in differentiation of Friend cells and we concluded that normal down-regulation of c myb expression may be a necessary event in differentiation of these cells. PMID- 2577876 TI - Transforming growth factor type beta 3 maps to human chromosome 14, region q23 q24. AB - Type beta transforming growth factors (TGF-betas) are polypeptides that act hormonally to control the proliferation and differentiation of multiple cell types. Recently, we reported the isolation of a cDNA encoding a new member of this gene family, which we have termed TGF-beta 3. Here we show by Southern analysis using a human probe specific for TGF-beta 3, the presence of a related single copy gene in a wide range of animal species. Chromosomal localization of the TGF-beta 3 gene was performed by Southern blot analysis of DNA prepared from 24 human-Chinese hamster somatic cell hybrids using a specific TGF-beta 3 cDNA probe. The human specific restriction fragments segregated only with human chromosome 14. For all other human chromosomes high discordancy scores were obtained. Using in situ hybridization of human metaphase chromosomes, the regional location could be identified. Hybridization of the TGF-beta 3 cDNA probe resulted in specific labeling of chromosome 14, bands q23-24. PMID- 2577877 TI - Resistance to retransformation by adenovirus but not by heterologous oncogenes in an E1-positive transformation revertant cell line may be mediated by a cellular function. AB - Using an indirect selection method based on drug-resistance, we have previously reported the isolation of flat revertants from adenovirus 2 transformed rat cells. Here, we demonstrate that one of these revertants has suffered a mutation in a cellular effector gene specifically required for the adenovirus-mediated expression of the transformed phenotype. Evidence for this conclusion includes the following: (1) the cells contain a 16-times amplified copy of the E1 region, thus reducing the chances of viral mutations, (2) the cells synthesized E1a and E1b proteins indistinguishable from those of the transformed parent, (3) the mutation has been stable for over 2 years, and most importantly (4) the revertant was resistant to re-transformation by E1 but not by c-myc, N-ras or polyoma middle t oncogenes. PMID- 2577878 TI - A region of the Epstein-Barr virus nuclear antigen leader protein and adenovirus E1A are identical. PMID- 2577879 TI - Application of restrained least-squares refinement to fiber diffraction from macromolecular assemblies. PMID- 2577880 TI - Current status of radioimmunoglobulins in the treatment of human malignancy. AB - Radioimmunoglobulin therapy is a new treatment modality that is easily administered, well tolerated, and can be given on an outpatient basis. It is not, however, as simplistic an approach to cancer therapy as commonly thought. It incorporates the sciences of immunology, physiology, radiobiology, chemistry, and physics, as well as oncology, all of which must be understood if radioimmunoglobulin therapy is to reach its potential. Partial and complete remissions have been achieved while the clinical teams involved in this research are still in the process of defining materials, methods, and future clinical approaches. The authors enumerate the varied problems in the development of radioimmunoglobulin therapy, and report on the current status of clinical trials. PMID- 2577882 TI - Can fat intake be lowered sufficiently to reduce risk of breast cancer? An interview with Ernst Wynder. Interview by Charlotte Kotkiewicz. PMID- 2577881 TI - Conservative management of invasive rectal cancer: alternative to abdominoperineal resection. AB - The standard treatment for patients with distal invasive rectal cancer who are unable to undergo a low anterior resection (LAR) is an abdominoperineal resection (APR). Although an APR offers excellent cure rates, it is associated with complications such as urological dysfunction, male impotence, and requires a permanent colostomy. Local excision alone is not adequate. If there is no evidence of gross disease in the pelvis, sphincter-sparing surgery (with negative margins) with adjuvant pelvic radiation therapy may be an alternative to abdominoperineal resection. Further follow-up will be needed to determine if this approach ultimately achieves local control and survival rates similar to an APR. PMID- 2577883 TI - Management of intestinal obstruction in ovarian cancer. AB - Bowel obstruction often is a sign of progression of ovarian carcinoma and is a major cause of death in this disease. Its treatment is still being debated. Options range from long tube decompression of the GI tract to bowel surgery. The authors review the management of bowel obstruction associated with ovarian carcinoma and provide guidelines helpful in selection of patients for surgical or medical management. Practical aspects of patient care are described in detail and the old adage "Never let the sun set or rise on a bowel obstruction" is examined in light of current surgical and medical management techniques. PMID- 2577884 TI - Recognizing and managing the late effects of cancer treatment. AB - Treatment for cancer too often adversely affects the very patients it is meant to help, especially children. Long-term damage can be found in the skeleton and soft tissues, in cardiopulmonary and renal function, and endocrine and neurologic function. The authors survey these late effects, including generalized growth suppression, dental and maxillofacial deficits, and pulmonary disorders, and suggest ways to prevent or alleviate them. PMID- 2577927 TI - [Long-term bougienage treatment of corrosive strictures of the esophagus]. AB - The value of long term bougienage of corrosive esophageal strictures is analysed in 21 patients. 67 bougienages have been performed with a 7.4 percent risk of perforation (5 cases), 4 patients whose symptoms were refractory to bougienage underwent operative therapy. Esophageal cancer developed in 2 patients and was operated in one of them. 70 percent of the 14 patients, who are still in the bougienage program report a good quality of life. We believe bougienage therapy of chronic corrosive esophageal strictures to be the method of choice in patients with high operative risk and satisfying response to the dilatations. PMID- 2577885 TI - Current management of non-squamous carcinoma of the cervix. AB - The incidence of non-squamous carcinoma of the cervix, relative to squamous cell carcinoma, seems to have been increasing over the past 15 years, and adenocarcinomas currently constitute 10 to 18% of cervical cancers. Uncertainties regarding the clinical behavior and management of women with non-squamous cervical cancer persist. Certain cell types and grade of adenocarcinomas play a role in prognosis and treatment selections. Treatment via irradiation or radical surgery for Stage I, small, garden variety cervical adenocarcinomas will result in excellent survival. Conversely, survival may be poor in early stage non squamous lesions if they are of high grade or of certain cell types, such as adenosquamous carcinoma. Patients with advanced cancers of other organ systems can now achieve an increase in progression-free interval with neoadjuvant chemotherapy or concomitant irradiation/chemotherapy. Such treatments might also benefit patients with non-squamous cervical cancers. PMID- 2577928 TI - Prognosis in synchronous colorectal carcinomas. AB - The prognosis of synchronous colorectal carcinomas is a matter of controversy. 5 year survival rates are reported to be either better or worse in comparison with single carcinomas. In this study 736 cases with histologically proven malignancies oft the large intestine were reviewed. 22 patients (3 per cent) showed multiple primary tumors. Patients with multiple tumors had associated adenomas in 72 per cent vs 14 per cent of the patients with single cancers (P < 0.01). 77 per cent of the synchronous tumors were located in the left colon. Only in 5 patients (23 per cent) two different lymphatic drainage areas were involved. 15 patients (68 per cent) presented without lymph node or distant metastases. A radical procedure was performed in 82 per cent. The overall 5-year survival rate was 54.5 per cent for multiple and 44.5 per cent for single carcinomas. The better survival rate seems to be due to the higher rate of early detection because of rectal bleeding in patients with synchronous tumors. PMID- 2577929 TI - [Bacterial hemoglobin degradation in feces--the cause of false-negative occult blood tests. Results of an in vitro study]. AB - Possible causes of false negative tests for occult fecal bleeding are hemoglobin concentrations too low to be detected or a bacterial degradation of fecal hemoglobin. In the present in vitro study the degradation of hemoglobin was assessed in cultures of fecal bacteria or in homogenates of human feces. At a hemoglobin concentration of 1.5 mg per gram stool a 48 h incubation caused a decrease of test positivity for hemoglobin of 88% (aerobic conditions) or 52% (anaerobic conditions). Thus, bacterial degradation is one of the causes of false negative test results when testing for occult fecal bleeding. These findings should be considered by the clinician when the efficiency of currently available occult blood tests in detecting right sided colonic lesions is to be assessed. PMID- 2577930 TI - [Comparison of quantitative liver function tests to clinical, laboratory chemical and biopsy findings in patients with liver diseases]. AB - Quantitative liver function tests (QLFT), e.g. 1) galactose elimination capacity (GEK) and 2) fractional indocyanine-green elimination constant k (ICG) were performed in patients with various liver diseases. Retrospectively the results of QLFT were compared to clinical, histological and laboratory findings which are known to reflect severity of liver disease. Patients showing clinical symptoms like ascites and/or encephalopathy demonstrated lower values for GEK and ICG. In addition similar data were obtained for those patients who showed histological evidence of cirrhosis. When dividing up the group of cirrhotics according to PUGH's classification, correspondingly lower results of QLFT were observed between different PUGH classes, however, due to a substantial overlap an individual classification could not be achieved by QLFT. Compared to routine laboratory tests which might estimate hepatic functional impairment the following correlations were found: GEK to albumin: r = 0.47, p < 0.01, to Quick: r = 0.44, p < 0.001, to bilirubin: r = -0.23, p < 0.05, ICG to albumin: r = 0.45, p < 0.01, to Quick: r = 0.53, p < 0.001, to bilirubin: r = -0.42, p < 0.001. No correlation could be demonstrated to transaminase activity. The results obtained support the view that QLFT are capable of estimating hepatic function, however, compared to conventional characteristics of advanced liver disease only moderate correlations were detected. A superiority of quantitative liver function tests could not be detected. PMID- 2577931 TI - [Rheumatologic syndrome in gastrointestinal diseases. Clinical and pathogenetic aspects]. AB - Patients with reactive arthritis, sacroiliitis, spondylitis or Reiter's syndrome following intestinal infection from Yersinia, Salmonella, Shigella or Campylobacter organisms have been reported from endemic areas and after epidemic dysenteries. Possession of the antigen HLA B27 affects severity and prognosis of the arthritis and is more often associated with spondylitis and Reiter's syndrome. Articular manifestations are also quite common systemic complications of chronic inflammatory bowel disease. The clinical picture, pathogenetical aspects and treatment of arthritis associated with Crohn's disease, ulcerative colitis and Whipple's disease are reviewed. In only few cases, coeliac disease can be complicated by arthritis. In patients undergoing intestinal bypass surgery systemically absorption of intestinal bacterial antigens and immune complex formation may contribute to the development of bypass-arthropathy and dermatologic manifestations. PMID- 2577932 TI - [A specific surface antigen of intestine-associated lymphocytes]. PMID- 2577933 TI - [Principles of particle resorption in the gastrointestinal tract]. PMID- 2577935 TI - Practice activity analysis. PMID- 2577934 TI - A cytochemical study of myeloid bodies in the retinal pigment epithelium of the newt Notophthalmus viridescens. AB - It has been suggested (Yorke and Dickson 1984) that myeloid bodies (MBs) in the retinal pigment epithelium (RPE) of the newt, Notophthalmus viridescens, may represent areas of endoplasmic reticulum where lipids, such as 11-cis retinal derived from phagocytized outer segment tips, accumulate prior to esterification. Experiments in which an artificial ester substrate was added during in-vitro incubations have shown that esterase activity is represented in all areas of the newt RPE endoplasmic reticulum, including sites adjacent to all MBs. In related tests in which the localization of enzyme activity was restricted to areas of the cell where there had been accumulations of naturally-occuring (endogenous) esters, the products of ester hydrolysis were restricted to profiles of endoplasmic reticulum associated with lipid droplets, and with the interior of about 20% of those MBs that appeared completely circular in sections. This enzyme activity was not associated with other MB configurations. Results from endogenous ester hydrolysis were identical to those obtained after staining with ZIO. This ZIO-reactive was not affected by pre-incubation with agents that blocked or protected sulphydryl groups, and ZIO-reactive sites associated with MBs did not form complexes with digitonin. These observations suggest that MBs are a site of lipid-ester formation, but that they do not represent unique intracellular areas for this activity. PMID- 2577936 TI - The contribution of academic general practice to undergraduate medical education. PMID- 2577937 TI - Statistical methods in cancer research. IARC Workshop 25-27 May 1983. PMID- 2577938 TI - An atlas of bedside microscopy. PMID- 2577939 TI - Working together--learning together. PMID- 2577940 TI - Course organizers in general practice. AB - In August/September 1984 a survey of the 267 course organizers in post in England and Wales was carried out. Eighty-two per cent replied to a questionnaire asking for details about their work and personal status. All 16 regions in England and Wales completed a questionnaire about levels of staffing and remuneration of those involved in general practice postgraduate education. The results show that there are considerable variations between regions in the role and responsibilities of course organizers, in their training, and in the facilities that are provided for them. The majority of course organizers reported a workload greater than the number of sessions for which they were remunerated. The effects of these factors on recruitment, tenure of post, and job satisfaction are discussed. Recommendations are made for improving the situation, including the removal of course organizer pay from the scale of trainers' pay, so that there can be flexibility in the number of sessions which can be held, improvement in training and certain facilities, and the implementation of national and local job descriptions. PMID- 2577941 TI - Continuing education for general practitioners. AB - This research was conducted to investigate patterns of attendance at continuing education meetings and examine which factors encourage or inhibit attendance by comparing the characteristics of general practitioners who attend regularly with those who attend occasionally or not at all. The findings provide course organizers with a detailed insight into the attitudes and perceptions of frequent and infrequent attenders. The research identifies a need for greater personal contact in changing attitudes to continuing education and bringing about greater involvement. It is concluded that the role of general practitioner tutor should be enhanced to provide more direct contact and influence with small groups of doctors. PMID- 2577942 TI - Priority objectives for general practice vocational training. Oxford Region Course Organizers and Regional Advisers Group. PMID- 2577943 TI - Booking for maternity care. A comparison of two systems. PMID- 2577944 TI - [Is an obsessive-compulsive disorder in children an anxiety disorder?]. AB - Concerning the update reconsideration of anxiety disorders of children, should childhood obsessive-compulsive disorder be assimilated as an anxiety disorder? Authors attempted to answer to this question by taking into account various levels of consideration which lead them to position childhood obsessive compulsive disorder in the vicinity of anxiety disorders. PMID- 2577945 TI - [Acute paroxysmal anxiety in children]. AB - Authors study acute anxiety disorders in children. They distinguish two clinical forms, depending on the knowledge of outer triggering factor: anxious paroxysm and panic attack. PMID- 2577946 TI - [Suicide prevention: past, present and future]. AB - Efforts to prevent suicide are reviewed. Recent studies have shown that suicide prevention centers may be effective in preventing suicide, at least among females. However, in recent years, more attention has been directed toward the possibility that restricting access to methods for suicide may be an effective way for preventing suicide. In addition, there is a growing body of research on which medications and which techniques of psychotherapy may be most effective in decreasing the risk of suicide in depressed patients. PMID- 2577947 TI - [Crisis intervention in the emergency service of a general hospital]. AB - Two general hospitals of Brussels tapped, in 1977, 47% of all the emergency ambulance traffic. More than 50,000 patients were examined there in one year. A randomized sample of 12,000 records were analyzed. From this file, 1707 psychosocial cases were carried out. The study will follow the progression of the patients during this crisis situation. Statistic tests pinpoint that the most determining variable is the symptoms. Seven symptoms cover more than 95% of the interventions. These symptoms are: alcoholism, suicide attempts, abnormal behavior, psychologic complaints, somatic complaints, violence, drug-addiction. Statistical analysis reveals that the two most important variables to draws crisis interventions at the emergency room were the time used by patient and the frequency of call of the psychiatrist. Other variables used to draw up the progression of the patients were: way of arrival, diagnosis and final destination. PMID- 2577949 TI - Estimated mechanical properties of synergistic muscles involved in movements of a variety of human joints. AB - One of the most challenging aspects of biomechanical modelling is parameter estimation. Parameter values that define the nonlinear relations within the classic Hill-based muscle model structure have been estimated for a large number of muscles involved in movements of a number of joints. The technique used to estimate these parameters is based on combining information on muscle as a material with geometrical data on muscle-joint anatomy. The resulting relations are compatible with available human experimental data and with past modelling estimates. An estimation of the relative importance of the various synergistic muscle properties during dynamic movement tasks is also provided, aided by examples of muscle load-sharing as a function of optimization criteria including measures of position error, muscle stress and neural effort. PMID- 2577948 TI - An analysis of the sources of musculoskeletal system impedance. AB - When antagonistic muscles co-contract, the impedance of musculoskeletal systems to applied loads is known to increase. In this paper a physiologically-based, higher-order, nonlinear antagonistic muscle-joint model is utilized to clarify the sources of impedance modulation during a variety of tasks, ranging from resisting transient loads to holding steady loads to making fast movements in unpredictable surroundings. It is shown that impedance modulation occurs automatically as a function of the specific operating ranges utilized during a given task by each of four different muscle-joint mechanical relations. The relative contribution of each relation depends on the type of task, with impedance during quasi-static conditions sensitive to muscle tension-length and sometimes joint parallel elastic properties and during dynamic tasks dominated by the series element and muscle force-velocity properties. Elimination of any of these causes a decrease in built-in biomechanical capabilities. These findings raise questions concerning past theories on stiffness-impedance modulation which appear to underestimate the role of inherent biomechanical properties. PMID- 2577950 TI - A numerical method for simulating the dynamics of human walking. AB - This paper presents a general method for simulating the movement of the lower extremity during human walking. It is based upon two separate algorithms: one for single support (an open kinematic chain), and the other for the double support phase (a closed-loop linkage). Central to each of these is the recursive Newton Euler inverse dynamics algorithm, applicable, as given, to any serial, spatial linkage. For the unconstrained single support model, the Newton-Euler scheme is applied directly to numerically generate the equations of motion. In the case of double support, however, the kinematic constraint equations are used to first eliminate the redundant degrees of freedom, and then solve for the unknown ground reactions under the constrained limb. The attractiveness of the method is that it offers a compact alternative to manually deriving the equations defining a mathematical model for human gait. PMID- 2577951 TI - Synthesis of human walking: a planar model for single support. AB - A mathematical model for the single support phase of normal, level, human walking is formulated. The motion of the lower extremity is synthesized using a preprogrammed set of inputs, recognized by the model as a simple collection of applied joint moments. Two mechanisms are forwarded as candidates for producing the observed peaks in the vertical ground reaction. The first, stance knee flexion-extension, generates the necessary level of whole-body vertical acceleration during the initial region of single support (opposite toe-off to heel-off). A model accounting for the determinants of foot and knee interaction then predicts the second peak to be the result of an increasing ankle moment in the region from heel-off to opposite heel-strike. PMID- 2577952 TI - An experimental and analytical study of impact forces during human jumping. AB - Impact forces during landing in dismounts from the horizontal bar onto regulation gymnastic mats and in jumping from a height of 0.45 m onto a hard surface were measured. A two degree-of-freedom dynamic model was developed to predict the forces in landing on the hard surface. The periods of the two peaks that can be identified from experimental data were used in the determination of the system parameters. The peak forces recorded in gymnasts' landing ranged from 8.2 to 11.6 times the body weight. Maximum forces in jumping from 0.45 m, which ranged from 5.0 to 7.0 times the body weight, were accurately predicted by the model. PMID- 2577953 TI - The biomechanical relation between incisal and condylar guidance in man. AB - The arrangement, form and movement of incisal and condylar guidance allow representation of the stomatognathic system by a gearing with positive drive and closed linkage. Because of problems of stability, this gearing has to be a throttle crank. Therefore, the stomatognathic elements have to fulfill the condition of Grashoff. The analysis of 14 Class I patient data confirms this condition and yields that their stomatognathic systems seem to be determined by only two parameters. The properties of these systems are largely independent of the jaw's growth if the momentary growth takes place in the direction of the initial inclination of hinge-axis movement out of centric relation. PMID- 2577954 TI - The neuropeptide head activator loses its biological acitivity by dimerization. AB - On molecular sieve columns the neuropeptide head activator elutes at two distinct positions corresponding to apparent mol. wts of 700 and 1400 daltons. The low mol. wt component is stable only under high ionic conditions and represents the monomeric state of the head activator. Only this form is biologically active. The higher mol. wt component, which is reapidly formed under physiological conditions, is the dimeric head activator and is biologically inactive. We suggest that this dimerization is of biological relevance as a mechanism for inactivation of neuropeptides. PMID- 2577955 TI - [IGFs/somatomedins: physiological and physiopathological significance]. PMID- 2577956 TI - [Diabetes and pregnancy: management and results for the period 1981-1984]. PMID- 2577959 TI - [The silent allele of complement C4 BQ0 is associated with increase risk if insulin-dependent diabetes (IDDM)]. PMID- 2577957 TI - [Monozygotic twins and genetic aspects of diabetes]. PMID- 2577958 TI - [Hypotheses on the etiology of insulin-dependent diabetes: published and recent ideas]. PMID- 2577960 TI - [Mechanism and genetic control of the autoimmune response directed against beta pancreatic cells in insulin-dependent diabetes]. PMID- 2577961 TI - [Glomerular hyperfiltration during sugar diabetes]. PMID- 2577962 TI - [Glucose and insulin in glucose homeostasis in the liver]. PMID- 2577963 TI - [Metabolic and immunologic effects of cyclosporine administration in new insulin dependent diabetics]. PMID- 2577964 TI - [Immunologic parameters and HLA groups in 50 Portuguese families with insulin dependent diabetes. Clinical and laboratory correlation]. PMID- 2577965 TI - [Conclusions of the study of genetic syndromes with extreme resistance to insulin]. PMID- 2577966 TI - [History of diabetic associations. Point of view of the Karen Bruni Center of Turin]. PMID- 2577967 TI - [Role of the gastric phase of digestion on the bioavailability of carbohydrates and their metabolic effects]. PMID- 2577968 TI - [Food technology and bioavailability of starch]. PMID- 2577969 TI - [Dietary fats and prevention of atheroma in diabetes]. PMID- 2577970 TI - [Vegetable fiber and diabetic diet]. PMID- 2577971 TI - [Do simple sugars have a place in the diabetic diet?]. PMID- 2577972 TI - [Apollinaire Bouchardat Award 1984. In vivo measure of glucose and amino acid metabolism by continuous perfusion of substrates labelled with stable isotopes]. PMID- 2577973 TI - [Apollinaire Bouchardat Award 1985. Insulin receptor: oligomeric structure and molecular interactions with major histocompatibility complex antigens]. PMID- 2577974 TI - [Action of metformin in insulin resistance]. PMID- 2577975 TI - [Physiopathology of non insulin-dependent diabetes. Action of gliclazide]. PMID- 2577976 TI - [Hormones of counter-regulation and metabolism of carbohydrates]. PMID- 2577978 TI - [Regulation of glucose utilization in vivo in man]. PMID- 2577977 TI - [Role of gastrointestinal hormones in carbohydrate metabolism]. PMID- 2577979 TI - [Intensive insulin therapy by multiple sub-cutaneous injections or CSII: indications and role of diabetic patient education]. PMID- 2577980 TI - [Beneficial effect of insulin therapy by pump on the development of diabetic retinopathy]. PMID- 2577981 TI - Synthesis and calcium channel antagonist activity of alkyl cycloalkyl esters of nifedipine containing pyridinyl substituents. AB - Alkyl cycloalkyl esters of nifedipine (1a) analogues, in which the ortho nitrophenyl group at position 4 is replaced by pyridinyl (5-19) were synthesized and evaluated as calcium channel antagonists using the muscarinic receptor mediated Ca(2+)-dependent contraction of guinea pig ileal longitudinal smooth muscle. The relative activity profile for unsymmetrical esters (5-15), which indicated the effect of cycloalkyl ring size on activity, was cyclopentyl > cyclohexyl > cyclobutyl. In addition unsymmetrical esters, possessing one R2 cyclohexyl substituent, exhibited an activity profile dependent upon the nature of the R1-alkyl ester substituent with Me > Et, i-Pr, i-Bu > cyclohexyl > t-Bu. The point of attachment of the C-4 pyridinyl substituent was also a determinant of activity for unsymmetrical compounds (R1 = Me, i-Pr; R2 = cyclohexyl, cyclobutyl) where the relative potency order was 2-pyridinyl > 3-pyridinyl > 4 pyridinyl. In contrast, when the R1 and R2-substituents are larger in size (R1 = R2 = cyclohexyl or R1 = i-Pr, R2 = cyclopentyl) the relative activity profile was 3-pyridinyl = 4-pyridinyl > 2-pyridinyl. The C-3 and C-5 ester substituents therefore appear to provide important interdependent contributions to calcium channel antagonist activity, and hence to interaction with the 1,4 dihydropyridine receptor site. PMID- 2577982 TI - Enzyme replacement therapy in porphyrias--V. In vivo correction of delta aminolaevulinate dehydratase defective in erythrocytes in lead intoxicated animals by enzyme-loaded red blood cell ghosts. AB - Resealed erythrocyte ghosts are potential in vivo carriers of exogenous therapeutic enzymes. In the present work, the effect of administering delta aminolaevulinate dehydratase (ALA-D) encapsulated in autologous red blood cell ghosts (RBCg) to lead intoxicated and normal mice was investigated. Administration of ALA-D loaded RBCg to intoxicated mice produced an immediate and permanent recovery in erythrocytic ALA-D activity; the effect was also noticeable in liver and spleen and absent in kidney, indicating that the entrapped enzyme was significantly stabilized to allow retention of activity in both circulating and phagocytized cells. Administration of ALA-D loaded ghosts to normal mice did not produce significant changes in ALA-D activity in blood, liver, spleen or kidney. Administration of free exogenous enzyme or blood transfusion during lead intoxication was also ineffective; spontaneous recovery of the poisoned animals was very slow. We show that circulating as well as phagocytized ALA-D entrapped in autologous erythrocyte ghosts can be safe and beneficial in the treatment of lead poisoning. Clinical trial in patients is recommended. PMID- 2577983 TI - Tumor-localizing properties of porphyrins. In vitro studies using the porphyrin precursor, aminolevulinic acid, in free and liposome encapsulated forms. AB - Tumor, liver, skin and brain explants from tumor-bearing mice were cultured for 6, 12 and 22 hours in the presence of 0.06, 0.1 and 0.2 mM aminolevulinic acid (ALA). It was found that in all organs, synthesis of porphyrins increased with time and ALA concentration. The synthesising activity of tumor was high, of the same order as that of liver, and nearly twice that of skin and brain. The tissue/tumor porphyrin concentration ratios were lower than 0.5 at longer times and higher ALA concentration. In the case of skin/tumor the lowest ratio was about 0.2 and was obtained with 0.2 mM ALA. Chromatographic analysis of individual porphyrins showed that the whole heme pathway was functional in all organs studied, including tumor. Porphyrin synthesis by different organs from tumor bearing and normal mice was comparatively investigated using free and liposome encapsulated ALA. After 22 hours of incubation with 0.4 mM ALA, porphyrin formation was greater when encapsulated ALA was used. Accumulation of porphyrins in tumor was very high. The levels of activity were the same in each pair of organs in either the tumor-bearing mice or the control. These results indicate that free or encapsulated ALA may be used for the detection of tumors and in photodynamic therapy. PMID- 2577984 TI - Scleroglucan sustained-release oral preparations. Part I. In vitro experiments. AB - Experiments performed in vitro with tablets and capsules indicate that the fungal polysaccharide scleroglucan is suitable for the formulation of sustained-release, oral dosage forms. Delivery of model drugs from the non-disintegrating matrix was studied in solutions buffered at different pH values. The effect on drug release of drug concentration, the physico-chemical properties of the drug, and the compression force used in the preparation of the matrix are reported, and the possible mechanisms of release are discussed. PMID- 2577985 TI - Promoting effect of 2-n-alkylcyclohexanones on the percutaneous absorption of indomethacin. AB - We previously evaluated the promoting effects of 2-tert-butylcyclohexanone and its analogues on the percutaneous absorption of indomethacin (IMC), and showed that the 2-position of the cyclohexanone ring plays an important role in drug permeability through the skin. The present study investigates the in vitro penetration enhancement of IMC by five 2-n-alkylcyclohexanone derivatives. 2-n Octylcyclohexanone was the most effective enhancer, but the other four enhancers also had significant promoting actions on skin permeability of IMC. Maximum absorption enhancement was associated with a defined range of enhancer lipophilicity. We propose that the enhancer penetrates into the stratum corneum and improves skin permeability of a drug by dissolving some of the hard lipid components or modifying the dense lipid stratum corneum. PMID- 2577986 TI - Application of PHYCON 6600 to achieve sustained release of an antitumor drug (carmofur). AB - This study attempted to develop sustained release implantable dosage forms based on PHYCON 6600, a new silicone gel. The solid gel is prepared at ambient temperature by polymerization of two basic components (PHYCON A and PHYCON B solutions) for about 1 h. The application we explored was the use of implantable PHYCON-drug composites in tumor therapy. Carmofur (1-hexylcarbamoyl-5 fluorouracil, HCFU) was chosen as a practical antitumor drug. Using an in vitro dissolution test, near zero-order release rate was observed over a period of about 35 days. The amount of drug released by the 'burst phenomenon' was found to be less than the HCFU toxic dose. In vivo studies of antitumor activity were carried out by measuring the lifespan of lymphoma-inoculated mice (ILS). The increase in lifespan (38.5%) following intraperitoneal administration of the PHYCON formulations was similar to that (36.4%) following injection of the drug alone for 5 days. Our results suggest that the injectable and implantable sustained release formulations of the antitumor drug in PHYCON might be suitable for tumor chemotherapy. PMID- 2577987 TI - Buoyant sustained release granules based on chitosan: comments on the article by Inouye et al. PMID- 2577988 TI - A QSAR study on renin inhibitors. AB - Quantitative structure-activity relationships (QSAR) were studied in a series of chain-modified peptide analogues of the active site of angiotensinogen. The activity of these renin inhibitors was found to be significantly correlated with Kier's first-order valence molecular connectivity index (1 chi v) and with the molecular weight (MW) of the molecules. The activity was less well correlated with the van der Waals volume (Vw), and not at all with the hydrophobic character (log P) of the molecules. These findings suggest that there is a strong dispersion interaction between the inhibitor molecules and the enzyme, and that hydrophobicity plays little part in the interaction. PMID- 2577989 TI - QSAR study of phosphodiesterase inhibitory activity of imidazo[2,1-b] quinazolines: active site analysis. AB - Published c-AMP phosphodiesterase inhibitory activities of 7-substituted-1,2,3,5 tetrahydro-2-oxoimidazo[2,1-b]quinazolines are used in a QSAR study to analyse a proposed model of the c-AMP PDE (type IV) active site. Based on the regression equations involving hydrophobic parameters and activities, additional subsites G1 and G2 are identified in the secondary binding region G, and steric hydrophobic tolerance at these subsites is discussed. PMID- 2577990 TI - Chemical delivery systems for drugs containing an amino group: synthesis and properties of some pyridine derivatives of desipramine. AB - Seven chemical delivery systems (CDS) based on a dihydropyridine<-->quaternary pyridinium salt type redox system and analogous to the naturally occurring NADH<- >NAD+ coenzyme system were applied in the case of the antidepressant drug desipramine. The pyridine moiety-containing carriers were linked to the amino function of desipramine either as amides or substituted carbamates. Lipophilic properties were expressed in terms of chromatographic Rm values. Oxidative stability of the dihydropyridine forms of the CDSs were determined in vitro. The amide type derivatives were stable toward hydrolysis in buffers and in biological fluids, whereas the carbamates released the parent drug in a very efficient manner. In a behavioral despair test, the CDSs did not show improved activity when compared to desipramine. In vivo distribution studies of one of the CDS did not show more efficient delivery of the desipramine into the rat brain but did show a prolonged presence at a constant level. PMID- 2577991 TI - Analysis of DNA fingerprinting data in cases of disputed paternity. AB - DNA fingerprinting is proving to be of great use in the establishment of the relatedness between individuals. Models are presented to assess the probabilities of DNA fingerprints as a means of establishing the paternity of a disputed offspring. The simplest models make a variety of unrealistic assumptions and an outline is presented of how the assumptions of fingerprint band population frequency equality and mutation rate constancy can be relaxed to produce a more realistic and powerful model. PMID- 2577992 TI - Steady-state spatial patterns in a cell-chemotaxis model. AB - We investigate a simple cell-chemotaxis model for the generation of spatial patterns in cell aggregations. For simple boundary-value problems, we analyse the local and global bifurcation of spatially heterogeneous patterns away from the uniform equilibria as the total number of cells is varied. We also discuss the existence of periodic spatially structured solutions for the cells and chemoattractant in the infinite domain. PMID- 2577993 TI - An automatic algorithm for immunoassay curve calibration using controlled quadratic splines. AB - An algorithm is described for the calibration of immunoassay curves. It employs a quadratic spline as the approximating function. The number and positions of the knots of the spline are chosen adaptively. The behaviour of the spline is controlled so that it preserves the key properties of the underlying function. PMID- 2577994 TI - Epidemics in heterogeneous populations: aspects of optimal vaccination policies. AB - Three models for epidemics among m groups with applications to human disease, especially socially and geographically heterogeneous populations, are considered. It is shown that the initial growth of each is an increasing function of the Frobenius root of R0, the matrix of reproductive ratios. A new way of looking at optimal vaccination is presented by linking policies to the growth rate of a new epidemic. Aspects of how to minimize the initial growth rate are analysed. In particular, we see that, when R0 has positive eigenvalues, we can find an explicit solution for the final optimal policy, and that there exists an extension of this policy which always gives the least possible growth rate at all stages of vaccination. PMID- 2577995 TI - A methodological study of a nonlinear stochastic model of an AIDS epidemic with recruitment. AB - A nonlinear stochastic model of an AIDS epidemic with recruitment of infectives, susceptibles, and AIDS cases into a randomly mixing population of male homosexuals was formulated and studied from a methodological point of view through intensive computer experimentation. Probability generating functions were used to formulate a model for the monthly probability that a susceptible individual becomes infected with HIV, under the assumption that the probability of infection per sexual contact varies as a function of the duration of infection. A method for taking into account the use of condoms to prevent infection with HIV was also introduced. Nonlinear difference equations, resembling deterministic epidemic models, were embedded in the stochastic population process by iterating an initial conditional expectation. Examples of Monte Carlo experiments are presented, illustrating that solutions of these nonlinear difference equations are not always good measures of central tendency for variations in the sample functions of the process. Two important substantive conclusions drawn from the Monte Carlo experiments were that efforts should be made to collect quantitative information on the probability of infection per sexual contact as a function of duration of infection and the frequency of condom use within and among risk categories in a population. PMID- 2577996 TI - A two-type population epidemic problem. AB - We consider a two-type population such that the birth rate of the second type depends on the size of the population of the first type. This problem was formulated by Kendall (1949) and Goodman (1953), then solved for constant parameters by Tapaswi & Roychoudhury (1984) and Gani & Tin (1984) (where the first type was female, and the second type, male). We generalize the known results to cases where the parameters are time dependent. Analytic expressions for the first two moments are found. For constant parameters, we derive the asymptotic law for the process. PMID- 2577997 TI - Trials, tribulations, and triumphs of the EM algorithm in pedigree analysis. AB - The EM algorithm is an iterative method for finding maximum-likelihood estimates. Its advantages often include numerical stability, simplicity of computer implementation, and natural incorporation of parameter constraints. However, the EM algorithm must be tailored to each specific problem. Smith (1957) and Ott (1977, 1979) have accomplished this for a variety of problems in human pedigree analysis. The present paper clarifies their theory by presenting it from a modern perspective. Five practical numerical examples are also given in an attempt to assess the value of the EM algorithm in realistic genetic modelling. These examples deal with racial admixture, linkage homogeneity, classical segregation analysis, a Mendelian latent trait model for schizophrenia, and a heterozygote detection assay for Ataxia-telangiectasia. Comparison with a quasi-Newton method of optimization reveals that the EM algorithm generally converges more slowly, but also more stably. PMID- 2577998 TI - On the role of variable incubation periods in simple epidemic models. AB - The paper formulates a simple stochastic model which can be used to describe the early spread of an epidemic in a large population. Comparison of the behaviour of the epidemic under different assumptions for the distribution of the incubation period are made using the concept of partial ordering between random variables. It is shown that the process describing the infectious contacts between individuals has a major effect on the comparison of the different models. These results have important implications for modelling the AIDS epidemic. PMID- 2577999 TI - Drawbacks of selection methods for synchronous cell growth: simulation techniques. AB - Investigations of Koch & Schaecter's (1962) model for the fission of a bacterium were carried out to resolve some conflict in the findings due to Takahasi et al. (1968) and Marr et al. (1969). A computer simulation procedure was used to reexamine the work of Takahasi et al. Our results confirm their findings that a simple formulation of Koch & Schaecter's model predicts a synchronous growth curve which fits the data reasonably well. This contrasts with the predictions of a poor fit given by the complex formulations of Marr et al. However, there is a disagreement between our results and those obtained by Takahasi et al. It involves a relationship between independence of the life length of daughter and mother cells and the degree of synchrony in growth. The practical implications of the simulation results are that selection methods are unlikely to give perfect synchrony. PMID- 2578000 TI - The generalized equation for the radiotracer clearance method of measurement of regional microcirculation. AB - The intratissual diffusion of a tracer and the geometry of the detection system are considered and a generalization of Kety's equation for the measurement of regional microcirculation is derived. Non-monoexponential shapes of time-activity curves are examined and explained. PMID- 2578001 TI - [Respiratory Diseases of the Environment. Conference proceedings. Positano, Italy, 24 April-2 March 1987]. PMID- 2578002 TI - Oncogene detection at the single cell level. AB - We describe strategies for the detection of oncogenes at the single-cell level and for the positive identification of under-represented oncogenic alleles in mixed populations of normal and tumor cells. By combining the Polymerase Chain Reaction (PCR) technique with a liquid hybridization and gel retardation assay, we have been able to detect H-ras sequences in single cells, including in one fertilized mouse ovum. We also describe a modification of the PCR protocol involving the use of mismatched primers. This procedure allows for the creation of novel Restriction Fragment Length Polymorphisms (RFLP) diagnostic of specific point mutations. This experimental approach has allowed us to detect ras oncogenes in a single heterozygous cell in the presence of 10(5) normal cells. PMID- 2578006 TI - Preventive care of the elderly: a review of current developments. Papers from the National Workshop on the Role of the Primary Care Team in Screening and Case Finding of Elderly Patients. Harrogate, March 1986. PMID- 2578003 TI - New biologic prognostic factors in breast cancer. AB - Long-accepted prognostic factors for breast cancer patients include the number of axillary lymph nodes positive for cancer; size of the primary; histopathologic features such as nuclear grade, histologic grade, and mitotic index; and the estrogen and progesterone receptor status. Unfortunately, these factors are relatively insensitive in predicting which women are particularly at risk of relapse. Newer discoveries which are or may be better prognosticators of a breast cancer patient's future course include growth factors, oncogenes, thymidine labeling index, and measurement of DNA ploidy status by flow cytometry. PMID- 2578007 TI - [Molecular genetics of juvenile diabetes]. PMID- 2578008 TI - [Possible role of opioid peptides in the control of energy homeostasis]. PMID- 2578009 TI - Potentiation and overshadowing in preweanling and adult rats. AB - Four experiments compared the aversion acquired by 18-day-old and 60-day-old rats to a flavor that was either tasted alone or in combination, simultaneously or successively, with another flavor when paired with illness. The purpose was to study temporal variables and theoretical issues pertinent to potentiation and overshadowing while investigating ontogenetic differences in these phenomena. When either the preweanlings or the adults were presented a simultaneous compound flavor (sucrose/coffee) followed by lithium chloride-induced illness, greater sucrose aversions were found than for animals conditioned on sucrose alone--that is, potentiation. Preweanlings demonstrated greater potentiation than did adults, whether the conditioned stimulus-unconditioned stimulus (CS-US) delay was 0 or 1 hr. This potentiation was eliminated by nonreinforced presentations of the alternative CS element. Potentiation was not seen when the two flavors were presented successively as the CS; instead, overshadowing occurred. Tests of configuring by extinction procedures indicated a tendency for these animals to form a configured representation of the simultaneous compound solution. This disposition for configuring tended to be more pronounced for preweanlings than for adults. Ontogenetic differences in response to configuration, CS saliency, and generalization decrement seem consistent with at least one model of potentiation and the ontogenetic differences in potentiation seen in the present experiments. PMID- 2578010 TI - Inhibition as a "slave" process: deactivation of conditioned inhibition through extinction of conditioned excitation. AB - Rats were used in a conditioned-suppression paradigm to investigate why a conditioned inhibition (CS-) does not extinguish when presented alone. Experiment 1 assessed the role of blocking by excitatory contextual cues and/or an evoked representation of the conditioned excitor (CS+), which had been nonreinforced in compound with the CS-. When the CS+ and context were extinguished prior to presentations of the CS- alone, the CS- showed a retardation effect, evidently reflecting latent inhibition, because no inhibition was detected in controls for which presentations of the CS- alone had been omitted. Experiment 2 showed that the loss of conditioned inhibition (CI) was due to excitatory extinction and not to time since conditioning. Furthermore, when excitation was reconditioned to the extinguished CS+ (Experiment 1), or to a novel CS in the same context (Experiment 2), CI was restored. Two other experiments evaluated whether the maintenance of CI depended upon excitation that was generic in form or associatively tied to the training context. They showed no loss of CI when groups received CS+ extinction in that context, along with concomitant presentations in a different context of the US by itself, for a novel CS, or correlated either positively or negatively with the original CS+. Collectively, the findings argue that CI is a "slave" to excitation, for when excitation is extinguished, CI is deactivated; and yet when excitation is reconditioned to the original or a new CS+ in the same or a different context, CI is restored. PMID- 2578011 TI - Relative novelty of conditioning context influences directionality of glycemic conditioning. AB - Previous experiments in which insulin was administered in a Pavlovian conditioning procedure obtained both hyperglycemic and hypoglycemic conditioned responses (CRs). In the present experiment the relationship of the conditioning context and the housing environment was varied. Two environments, wastebasket (WB) and metal cage (MC), were varied factorially as housing and conditioning contexts. Subgroups were injected with either insulin or saline for 6 days and then, on a test day for conditioning, all animals were administered saline. The results suggested that a hyperglycemic CR could be expected when the conditioning context is different from the housing context, but a hypoglycemic CR could be expected when the conditioning context and housing context are similar. The magnitude and reliability of conditioning were greater when it was conducted in the WB context than when conditioning was conducted in the MC context. These results are discussed in terms of stress arising from relative novelty of the conditioning environment and in terms of the salience of the conditioned stimulus (CS) used in glycemic conditioning studies. PMID- 2578012 TI - Clinical stages I and II Hodgkin's disease: a specifically tailored therapy according to prognostic factors. AB - The H5 program in clinical stage (CS) I to II supradiaphragmatic Hodgkin's disease (HD) was tailored to prognostic factors identified in former European Organization for the Research and Treatment of Cancer (EORTC) studies. Among the 494 adult patients included in the study, the 237 patients belonging to the favorable group (H5F) underwent a staging laparotomy (Sx) in order to select the patients who could be treated with limited radiotherapy (RT) only. Thus, 198 patients (84%) with negative laparotomy were treated with RT alone and randomized to either mantle irradiation (M) or extended field mantle plus para-aortic (M + PA) irradiation. Complete remission (CR) was achieved in 99% of the patients. There was no difference in the 6-year relapse-free survival (RFS) rate (74% and 72%, respectively) or survival rate (96% and 89%). Therefore, Sx helped to define those patients who could be treated with M alone in contrast to those who required more aggressive therapy. The 39 patients with positive laparotomy were treated as the unfavorable group (H5U) from onset and randomized to either total/subtotal nodal irradiation (TNI/STNI) or a sandwiched mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) X 3, M irradiation, MOPP X 3 protocol (3M). Although the RFS rate was higher in the 3M arm (100% v 53%; P = .002), the 6-year survival was not significantly different between the two arms (overall, 92%). In the 257 patients with initial unfavorable disease, the Sx was avoided. They were randomized to either TNI/STNI or 3M. In complete responders (96%), the 6-year RFS was 91% in the 3M arm and 77% in the TNI/STNI arm (P = .02). The pattern of failure differed in the two arms: the inverted Y and spleen irradiation controlled occult infradiaphragmatic disease better than MOPP; conversely, less patients begun on MOPP recurred in the involved mantle areas. The difference in 6-year actuarial total survival (TS) (89% and 82%; P = .05 in favor of the 3M arm) was not retrieved after exclusion of the unrelated deaths from the analysis. The two arms produced similar TS in patients under 40 years of age. TNI retains interest, especially in young men wishing to preserve fertility. The overall result shows that when treatment is tailored to initial prognostic factors, excellent results can be obtained in all patient subgroups at minimal morbidity and toxic cost. PMID- 2578013 TI - The effect of the secretory leukocyte protease inhibitor on leukocyte proteases released during phagocytosis. AB - The human secretory leukocyte protease inhibitor effectively binds and blocks the digestive activity of elastase released from PMN leukocytes during phagocytosis of opsonized yeast particles. About 25% of the alpha 1-protease inhibitor present in the incubation medium is inactivated during the phagocytosis, while the secretory leukocyte protease inhibitor retains more than 90% of its inhibiting capacity. PMID- 2578014 TI - Allergy testing. American College of Physicians. PMID- 2578015 TI - The left ventricular vibration mode in the ventricular transfer function method and at the moment of the first heart sound. AB - Several investigators have aimed to clarify the patient's left ventricular (LV) physical properties by free vibration analysis of heart sound. Recently we have developed a transfer function (TF) method to calculate the LV viscoelasticity. To clarify whether this TF method and a clinical first heart sound (1 HS) analysis are based on the identical ventricular vibration mode analysis, we examined (1) the visualized LV vibration image in the TF method and (2) the quantitative relationship between the peak frequency of the 1 HS spectrum and that of TF curve in the early and late phase of the 1 HS. Isolated isovolumic potassium arrested canine left ventricles were used to visualize the vibration mode in describing the TF (N = 2). Examination of stroboscopically illuminated, slow-motion images revealed the oscillation of the ventricle to be of mode 2 behavior. To analyze the quantitative relation between the TF method and 1 HS analysis we used ten open-chest dogs. The correlation was good (r = 0.917) when the peak frequency of the TF curve at the early phase of the 1 HS was compared to the peak frequency of the 1 HS. We concluded that both the TF method and 1 HS analysis were based on the common, second-order ventricular vibration mode. Therefore, some information on the ventricular physical properties suggeted by the TF method could also be included in the clinical data obtained by 1 HS analysis. PMID- 2578016 TI - [Viral hepatitis: clinical interpretation of antigens and antibodies in the serum]. PMID- 2578018 TI - Psychiatric assessment and temporal lobectomy. PMID- 2578017 TI - Breast cancer in relation to the occurrence and time of induced and spontaneous abortion. AB - The authors evaluated whether an induced or spontaneous abortion during the first six months of gestation, particularly if it occurs before the first term pregnancy, increases the risk of breast cancer. Data from a case-control study of women under 70 years of age were used: 3,200 cases of breast cancer were compared with 4,844 controls with nonmalignant nongynecologic conditions. Among both nulliparous and parous women, the risk of breast cancer was not related to the number of induced or spontaneous abortions. After allowance for all identified potential confounding factors, the estimated relative risk for nulliparous women with an induced abortion relative to those who had never been pregnant was 1.3 (95% confidence interval (CI) 0.8-2.2), and for spontaneous abortion, the corresponding estimate was 0.9 (95% CI 0.5-1.5). Among parous women, the estimated relative risks were 1.2 (95% CI 0.9-1.6) for an induced abortion and 0.9 (95% CI 0.8-1.0) for a spontaneous abortion, relative to never having had an abortion of any type. The time of the abortion had little effect: The relative risk estimates were 0.9 (95% CI 0.5-1.4) for induced abortion before the first term birth, 1.4 (95% CI 1.0-1.9) for induced abortion first occurring after the first term birth, 0.9 (95% CI 0.7-1.2) for spontaneous abortion before the first term birth, and 0.9 (95% CI 0.7-1.0) for spontaneous abortion first occurring after the first term birth. Similar results were evident for women under age 40, among whom the frequency of induced abortion was relatively high. These data suggest that the risk of breast cancer is not materially affected by abortion, regardless of whether it occurs before or after the first term birth. PMID- 2578019 TI - A state-by-state report from the CDC on deaths from breast cancer. PMID- 2578020 TI - Biology and treatment of small non-cleaved cell lymphoma. AB - Small non-cleaved cell lymphoma occurs predominantly in the first two decades of life, and in this age group can be divided into two major types, both of which are associated with non-random chromosomal translocations. The endemic form occurs at high frequency in equatorial Africa, and the sporadic form occurs at low frequency throughout the world. Treatment consists primarily of chemotherapy; surgery has an important role in resectable abdominal disease, but radiation is of limited value. Prophylactic treatment of the central nervous system is recommended in nearly all patients. The most effective regimens result in cure in almost all patients who have limited disease, and in a high proportion of patients with extensive disease. Patients with bone marrow or central nervous system involvement have a poor prognosis with most regimens. Therapy for recurrent disease continues to be a challenge, and remains largely experimental. PMID- 2578021 TI - Experimental approaches for the prevention of hematogenous metastasis. AB - With improvements in surgical procedures and cure rates, the probable course of cancer for the majority of patients is now largely determined by metastasis rather than growth of the primary tumor itself. Thus, metastasis has received increasing attention over the past decade. These studies have led to the identification of several of the molecular events crucial for metastatic dissemination, information which is now being used to design therapeutic strategies to inhibit metastasis formation. Even though the molecular events involved in the dissemination of malignant disease are only partially known, several promising agents are now being tested for their capacity to limit the spread of cancer. A few clinical trials have shown benefit in prolonging survival and disease-free state, particularly when such therapy is employed on an adjuvant basis. PMID- 2578022 TI - Aminopeptidase and cathepsin A activity in vitreous humor in relation to causes of death. AB - Brain autolysis happens rapidly, especially when environmental temperatures are high, and poses serious limitations for evaluating damage using morphologic methods. In the present study we have measured total proteins, cathepsin A and aminopeptidase activity in the vitreous humor in relation to cause of death and survival time. We have studied vitreous humor samples from 106 cadavers autopsied in the I.A.F. of Granada. The samples were classified according to causes of death as follows: myocardial infarction; hanging; other mechanical asphyxias; multiple trauma; craniocerebral trauma; other violent death; pulmonary functions; and other natural deaths. Total protein was measured by Lowry's method, and cathepsin A and aminopeptidase activity by the Bowen and Davison (1973) and Greenberg (1962) methods, respectively. Results are expressed in IU/l and in mIU/mg of protein. We found higher values of aminopeptidase and cathepsin A activity in groups with severe brain damage (craniocerebral trauma, multiple trauma, etc.) and lower values in groups of natural deaths. We believe, therefore, that aminopeptidase activity in vitreous humor may be a useful parameter for evaluating brain damage. PMID- 2578023 TI - Structural organization of the rat acyl-peptide hydrolase gene. PMID- 2578024 TI - Outpatient treatment of patients with chronic pain: an analysis of cost savings. AB - To control costs, the University of Tennessee Center for Pain Management added an ambulatory pain rehabilitation program to its existing inpatient hospitalization program. The impact of this program was assessed by comparing the first 25 patients treated in 1985 (prior to the introduction of outpatient management) with the first 25 patients treated in 1987 (after outpatient management was established). Twenty of the 25 patients seen in 1985 required hospitalization, while in 1987 nine patients were hospitalized and 10 patients were placed in outpatient rehabilitation. The total cost for treating 25 patients in 1985 was $571,200 but decreased to $191,000 in 1987. Hospital charges were the greatest single cost factor in 1985 ($321,500) but were only $61,000 in 1987. Success rates as measured by a return to previous employment were not significantly changed (13 of 25 returned to work in 1985, and 11 of 25 returned to work in 1987). PMID- 2578025 TI - Proposition 65. PMID- 2578026 TI - Reporting the proportions of variance explained (PVE) PMID- 2578027 TI - Helicopter rescues and deaths among trekkers in Nepal. AB - Trekking in Nepal is a popular recreational activity that involves approximately 45,000 persons each year. The health risk of trekking in Nepal has never been calculated. We retrospectively studied all helicopter evacuations and deaths among trekkers in Nepal between Jan 1, 1984, and June 30, 1987. A total of 148,000 persons obtained trekking permits during that time. Twenty-three persons died and 111 were rescued by helicopter. The risk of dying while trekking was 15 deaths per 100,000 trekking permits. The frequency of helicopter rescue was 75 per 100,000 trekking permits. The most frequent cause of death was trauma (11 persons), followed by illness (eight persons) and acute mountain sickness (three persons). Deaths occurred equally at all altitudes from 1000 m to over 5000 m, although the number of persons at risk at different altitudes could not be calculated. These data suggest that trekking in Nepal is a relatively safe activity, but a decision to embark on a trek in Nepal should be individualized, with an understanding of the problems related to remoteness, altitude, and illness in the absence of medical facilities. PMID- 2578028 TI - Conformational changes of cytochromes P-450cam and P-450lin induced by high pressure. AB - Absorbance and fluorescence spectra of bacterial cytochrome P-450cam and cytochrome P-450lin have been studied as a function of pressure. These pressure induced spectral perturbations fall into two categories, which are interpreted as resulting from denaturation domains and are discussed in terms of protein structural dynamics. The results presented herein support a view that these two bacterial cytochromes have large structural differences and suggest a picture in which the gellike cortex of each protein may play an essential role in stability and function. PMID- 2578029 TI - Mass spectrometric analysis of anatoxin-a. AB - Secondary ion mass spectrometry (SIMS), gas chromatography/mass spectrometry (GC/MS), desorption chemical ionization/mass spectrometry (DCI/MS), and thermospray/mass spectrometry (TSP/MS) were evaluated for the detection of a low molecular weight biological toxin, anatoxin-a. The lowest detection limit was obtained using isobutane or ammonia DCI/MS. Tandem mass spectrometry (MS/MS) was used to enhance the selectivity and sensitivity of the analysis. The detection limit for the pure material is 10 pg, and 100 pg of the toxin can be analyzed directly from urine using DCI/MS/MS. PMID- 2578031 TI - Comparison of immune response to rubella virus proteins in early and late natural infections. AB - The immunological response to rubella virus structural proteins was analyzed by immunoprecipitation assay in sera collected in Cordoba, Argentina, during early convalescence and after remote natural infections. All of the viral structural proteins, the two glycoproteins E1 and E2, and the nucleocapsid C protein, were precipitated by sera obtained from patients soon after infection. By contrast, C reactive antibodies were not detected in sera from remote infections. These results suggest that E1 and E2 play a major role in the long-lasting protective immunity to rubella virus. PMID- 2578033 TI - Newer drugs in management. Calcium antagonists. AB - Ca2+ ions are critical to the functions of the various cells involved in the pathogenesis of asthma. Interest has developed regarding the potential use of Ca2+ antagonists in the management of asthma and allergic diseases. The information accumulated to date suggests that Ca2+ entry blockers may decrease airway smooth muscle responses to contractile agonists and may also reduce chemical mediator release from mast cells. Both processes would be expected to modify favorably the pathophysiology of asthma. This seems to have been demonstrated with the findings that certain Ca2+ entry blockers may inhibit exercise-induced bronchospasm and cold air- and antigen-induced airway narrowing. In several but not all experiments a direct bronchodilating effect of nifedipine was found in some subjects. In asthmatic patients with coexistent cardiovascular disease requiring beta-blocker therapy, it would be appropriate to use drugs such as the currently available Ca2+ entry blockers in place of the contraindicated beta-blocking agents. It appears that the currently available Ca2+ entry blockers have not provided a breakthrough class of therapeutic agents for the treatment of asthma. However, it seems highly likely that new Ca2+ antagonist drugs can be expected which will have greater specificity for airway smooth muscle and perhaps other cell types involved in the pathogenesis of asthma. PMID- 2578032 TI - Regulation of airway secretions. PMID- 2578030 TI - The skin in diabetes mellitus. PMID- 2578034 TI - Prolactin-mediated progesterone secretion by cultured rat granulosa cells: regulation by purified human glycoprotein hormones and their subunits. AB - The effects of purified alpha- and beta-subunits of human glycoprotein hormones on initial luteinization and subsequent prolactin-mediated progesterone responses of cultured rat granulosa cells were studied. Granulosa cells, obtained from immature female rats 50 h after PMSG treatment, were incubated for 24 h in control medium lacking added hormones or in medium containing hCG or the alpha- or beta-subunit of human (h) FSH, LH, CG, or TSH at 0.1, 0.5, and 1.0 microgram/ml. Cultures were maintained subsequently for 6 days in medium containing 1.0 microgram/ml bovine PRL (bPRL), with medium changes every 48 h. Indices of luteotropic stimulation in response to bPRL were provided by 1) elevated progesterone concentrations determined by RIA of spent media samples, and 2) cytoplasmic lipid accumulation assessed by osmium tetroxide staining following fixation of monolayers after 7 days of culture. Progesterone concentrations in media from cultures incubated in 0.5 or 1.0 microgram/ml hCG were 6-fold higher than in cultures incubated in control medium, while those in media from cultures incubated in 0.5 or 1.0 microgram/ml hFSH alpha, hLH alpha, hCG alpha, hTSH alpha, hLH beta, or hCG beta (but not in hFSH beta or hTSH beta) were from 2- to 4-fold higher than those in control cultures. This enhancement was not evident when subunits were added to the incubation media at the lowest concentration. Progesterone secretion corresponded directly with the degree of cytoplasmic osmiophilia. These results suggest that the alpha-subunit of each of the glycoprotein hormones as well as the beta-subunit of hLH and hCG have the ability to promote progesterone secretion during initial luteinization and to regulate subsequent PRL-mediated steroidogenesis by rat granulosa cells in vitro. Furthermore, these effects are greater than can be accounted for by potential contamination of subunit preparations with undissociated hormones, as demonstrated by dose-response curves. PMID- 2578035 TI - Glycosylated human prolactin. AB - A glycosylated form of human PRL (G-hPRL) was isolated from pituitary glands. The glycoprotein was separated from the major form of PRL on columns of lentil lectin Sepharose 4B. The major form of PRL did not bind to the lentil lectin, whereas the glycosylated modification did and could be eluted with methyl-alpha-D mannopyranoside. By gel electrophoresis in sodium dodecyl sulfate, a mol wt of 25,000 was estimated for the glycosylated PRL. The mol wt of hPRL is 23,000. In a RIA for hPRL, the glycosylated hormone was about one third as reactive as the principal form. Since there is only one Asn-X-Ser(Thr) sequence in hPRL, the asparagine at position 31 is the likely point of N-linked glycosylation. PMID- 2578036 TI - Epidermal growth factor induces maturation of rat follicle-enclosed oocytes. AB - Gonadotropin-induced differentiation of ovarian granulosa cells in culture is inhibited by epidermal growth factor (EGF). The present study was undertaken to test a possible inhibitory effect of EGF on LH-induced maturation of rat follicle enclosed oocytes. We have found that EGF not only failed to affect LH action but served by itself as an inducer of maturation of follicle-enclosed oocytes. EGF action on the oocytes was dose and time dependent and could be prevented by (Bu)2 cAMP. The response of the oocytes was specific to EGF and could not be elicited by other growth factors such as nerve growth factor and insulin. The response to EGF was not limited to the large antral follicles, as oocytes enclosed by small antral follicles (less than 0.4 mm) were induced to mature by EGF as well. In addition, we have demonstrated that oocytes, induced to mature by EGF, are concomitantly uncoupled from the follicular cells. Based on these results we suggest that EGF may terminate the transfer of a follicular inhibitor to the oocyte. It is also possible, however, that EGF induces oocyte maturation by a mechanism independent of its effect on communication between the cellular components of the follicle. PMID- 2578037 TI - Effect of epidermal growth factor on the development of rat gastric mucosa. AB - Epidermal growth factor (EGF) has been shown to stimulate the growth of adult rat gastric mucosa and to increase DNA synthesis of mouse small and large intestinal mucosa. This study examines whether EGF affects the functional and structural development of the rat gastric mucosa. Rats were injected with 20 micrograms/kg EGF three times/day for 5 days beginning on the 10th day after birth. A control group of animals received saline injections of identical volume. All rats were killed on day 15. EGF significantly increased the weight of the whole stomach and the DNA, RNA, and protein content of the oxyntic gland mucosa, but had no effect on the RNA/DNA ratio, or antral and serum gastrin levels. Two groups of similarly treated rats, were anesthetized with ether, pylorus-ligated, and injected with either saline or pentagastrin (250 micrograms/kg) after they had recovered from anesthesia. EGF-treated rats had significantly higher rates of basal acid secretion and pentagastrin-stimulated acid secretion than the saline-treated controls. EGF, however, did not alter basal or pentagastrin-stimulated pepsin secretion nor did it change mucosal pepsinogen content. These results indicate that EGF stimulates oxyntic mucosal growth in unweaned rats but that it does not lead to precocious maturation or functional development. PMID- 2578038 TI - Enteroglucagon cell hyperfunction in rat small intestine after gut resection. AB - The ultrastructural characteristics of immunoreactive enteroglucagon cells from three groups of experimental rat models (i.e., massive small bowel resection alone, massive small bowel resection with bombesin infusion, and transection with bombesin infusion) have been investigated. The results show that the cells did not undergo significant change in size or in the area of cytoplasm. All three groups displayed highly significant decreases of between 200% and 400% in the area of cytoplasm occupied by the secretory granules (expressed as volume density) and highly significant increases between 150% and 200% in the area occupied by the rough endoplasmic reticulum. Significant decreases (7%-10%) in secretory granule diameter were found in the two bombesin-treated groups, whereas resection alone was without significant effect on granule size. These results indicate that the enteroglucagon cells in these three groups are in a hyperfunctional state. PMID- 2578039 TI - Effect of a meal on human whole blood serotonin. AB - Levels of whole blood serotonin and tryptophan were measured in 11 human subjects after the consumption of a meal. Blood samples were obtained at 30 and 15 min before the meal and at 15, 30, and 60 min postcibal. One-hour urine specimens were collected for 5 subjects at 0, 60, and 120 min. Whole blood serotonin and tryptophan and urinary 5-hydroxyindoleacetic acid were measured using specific high-performance liquid chromatographic methods. A precibal mean (+/- SEM) serotonin level of 136 +/- 8 ng/ml (n = 22) was observed; means at 15, 30, and 60 min after the meal were 138 +/- 20 ng/ml (n = 9), 145 +/- 18 ng/ml (n = 11), and 138 +/- 16 ng/ml (n = 11), respectively. At no time were postcibal levels of whole blood serotonin significantly higher than baseline levels (paired t-test). Urinary excretion of 5-hydroxyindoleacetic acid also was unchanged; mean hourly rates were 230 +/- 23 micrograms/h before the meal, and 196 +/- 17 micrograms/h and 190 +/- 33 micrograms/h (n = 5) during the first and second hour postcibal, respectively. The absence of a postcibal increase of serotonin in circulating whole blood indicates that serotonin is probably not a human gastrointestinal hormone in the usual sense. PMID- 2578041 TI - Specificities of antibodies to human growth hormone (hGH) in patients treated with hGH: longitudinal study and comparison with the specificities of animal antisera. AB - The specificities of human and animal antibodies (Abs) against human GH (hGH) were analyzed using competition experiments with five monoclonal antibodies to hGH (MAbs). The results indicate that 1) the Abs produced by patients receiving long term hGH therapy as well as Abs of goat, rabbit, and mouse origin recognized the various hGH epitopes defined by the MAbs; 2) the proportion of each Ab population, with a given specificity, differed markedly in different patients and also with time in the same patient; 3) the titer of certain Ab populations was very low in some patients, and 4) polyclonal mouse Abs and some human Abs enhanced the binding of [125I] hGH to insolubilized MAbs. PMID- 2578040 TI - Effect of substance P on somatostatin release from the isolated perfused rat stomach. AB - The effect of substance P (SP) on the release of gastric somatostatinlike immunoreactivity (SLI) was studied. Substance P inhibited both basal SLI release and SLI release stimulated by gastric inhibitory polypeptide or 1-isoproterenol. This inhibitory action of SP was not blocked by atropine or hexamethonium, suggesting that a cholinergic mechanism was not involved. The SP-suppressed SLI release was also not reversed by the administration of naloxone, which indicated that enkephalinergic involvement was absent. However, the SP antagonist [D-Pro2, D-Trp7,9]-SP abolished the inhibition of SLI release by SP. It is concluded that SP might be involved in the control of gastric SLI release and that the inhibitory action of SP was probably mediated directly or indirectly on the gastric D cells through SP receptors. PMID- 2578042 TI - Membrane vesicles shed by murine melanoma cells selectively inhibit the expression of Ia antigen by macrophages. AB - We previously demonstrated that membrane vesicles shed by the F10 variant of the murine B16 melanoma cell line inhibited the induction by interferon-gamma (IFN) of murine macrophage immune response region-associated (Ia) antigen expression. In this paper we present evidence that the inhibition of macrophage Ia antigen expression is a selective effect of vesicles and characterize its temporal requirements. Membrane vesicles shed from F10 cells did not affect the expression of macrophage H-2K or H-2D antigens under conditions shown to profoundly inhibit Ia antigen expression. Similarly, the induction of plasminogen activator and interleukin 1 from macrophages was not inhibited by the vesicles. The vesicles did not measurably decrease total cellular RNA or protein synthesis. Macrophages were sensitive to the inhibitory effects of the vesicles during the induction and maintenance phases of Ia expression. Pretreatment of macrophages with vesicles before culture with IFN did not reduce the induction of Ia. The rate of decline of Ia expression after removal of IFN was unaffected by the presence of vesicles. Removal of vesicles from cultures of IFN-treated macrophages resulted in only a partial recovery of Ia expression, suggesting that the inhibition of Ia expression may be a slowly reversible process. The selective and partially reversible inhibition of Ia expression by vesicles shed from the plasma membrane of tumor cells is a possible mechanism whereby tumor-bearing hosts may become immunocompromised. PMID- 2578043 TI - Differences in T15 expression of primary and secondary anti-PC responses with T cells from T15+ and T15- donors. AB - The expression of T15 idiotype dominance with T cells from T15- mice was investigated. It was found that T15 dominance in the T-dependent response to phosphorylcholine (PC) could be generated by unprimed BALB/c B cells with T cells from T15+ and xid T15- mice. T15 dominance was also expressed when T15 neonatally suppressed BALB/c were used as T cell donors. With PC-primed B cells, however, T15 dominance was not established until 3 wk after adoptive co-transfer with T helper cells from xid NBF1 mice. To further study the different efficiencies of T cells for T15 dominance, limiting dilution analysis was performed. The data demonstrate that T15-specific T cell populations in BALB/c mice and NBF1 male mice differ in their precursor frequencies. In BALB/c mice, a frequent set of T15/M167-recognizing T helper cells is present; a corresponding frequent set of cells is absent in NBF1 males. This difference is likely to be one of the reasons why dominance is not immediately established after transfer of T cells from xid mice. PMID- 2578044 TI - The human thymic microenvironment. Phenotypic characterization of Hassall's bodies with the use of monoclonal antibodies. AB - The human thymic microenvironment is important in promotion of T cell maturation, particularly during early stages of thymic ontogeny. Hassall's bodies (HB) are epithelial swirls in the human thymic medulla that are thought to be derived from endocrine medullary thymic epithelium. To study the ontogeny and function of various components of the human thymic microenvironment, we have produced four monoclonal antibodies (TE-8, TE-15, TE-16, and TE-19) that selectively reacted in thymus with HB. Antibodies TE-8 and TE-16 reacted with the cells forming the outer rim of the HB swirl. Antibody TE-19 reacted with the entire cellular portion of HB and with epithelial cells immediately surrounding HB. Granular foci in the cellular swirls of greater than 90% of HB reacted with antibody TE-15. During thymic ontogeny, the antigens defined by antibodies TE-8, TE-15, TE-16, and TE-19 were first detected in fetal thymus on HB beginning at 16 wk gestation, the age when HB morphologically appear in the thymus. Aberrant expression of the antigens corresponding to antibodies TE-8, TE-15, TE-16, and TE-19 was observed on thymic tissue from individuals with severe cellular immunodeficiency disease. In human skin, antibodies TE-8, TE-16, and TE-19 reacted with the stratum granulosum; antibody TE-15 reacted with the stratum corneum. Thus, with the use of antibodies TE-8, TE-15, TE-16, and TE-19, we have identified HB as antigenically distinct regions of endocrine thymic epithelium. Furthermore, we have shown that these anti-HB reagents also selectively react with epidermal keratinocytes in the terminal stages of keratinocyte maturation. PMID- 2578045 TI - Activation of human thymocytes via the 50KD T11 sheep erythrocyte binding protein induces the expression of interleukin 2 receptors on both T3+ and T3- populations. AB - Recent studies have demonstrated that the 50KD T11 molecule is a surface component of a macrophage-independent alternative pathway of human T cell activation that is unrelated to the T3/Ti antigen-MHC receptor complex. Given the expression of T11 on all human thymocytes, it was of interest to determine whether they could be activated via this pathway. The triggering of T11 by monoclonal antibodies anti-T112 and anti-T113, directed at two unique epitopes on the molecule, induced IL 2 receptor expression on both T3+ and T3- thymocytes but did not induce IL 2 production. Consequently, in contrast to peripheral blood T cells, thymocytes did not proliferate in response to anti-T112 and anti-T113 in the absence of exogenous IL 2. These studies suggest that IL 2 receptor gene activation precedes IL 2 gene activation in T cell development. The ability of the alternative pathway of T cell activation to induce IL 2 receptor expression on T3- thymocytes implies that the T11 molecule may have an important role in early thymocyte ontogeny. PMID- 2578046 TI - Studies on the synthesis and secretion of interleukin 1. I. A 33,000 molecular weight precursor for interleukin 1. AB - Previous studies have suggested that murine interleukin 1 (IL 1) may be synthesized as a high m.w. precursor. Using specific antibodies against murine IL 1, we have analyzed the primary form of IL 1 synthesized by normal peritoneal macrophages and P388D1 cell line macrophages, and in vitro using poly (A)+ RNA from stimulated normal and cell line macrophages. In all cases, the labeled protein immunoprecipitated with the anti-IL 1 antibodies exhibited a m.w. of 33,000 on SDS gels. This 33,000 m.w. protein was not an aggregate of low m.w. IL 1. Addition of excess purified low m.w. IL 1 completely blocked the immunoprecipitation of the 33,000 m.w. protein. When cells were pulsed with [35S]methionine for 1 to 5 hr and then incubated in medium containing unlabeled methionine for 19 hr, labeled low m.w. IL 1 was detected in the culture fluid. If cells were pulsed with [35S]methionine to label the 33,000 m.w. protein and then incubated in the presence of a maximally effective concentration of the protein synthesis inhibitor, cycloheximide, the low m.w. IL 1 was still found in the culture fluid. Our results indicate that IL 1 is synthesized as a 33,000 m.w. precursor that is converted to the low m.w. form that is found in the culture fluid of stimulated murine macrophages. PMID- 2578047 TI - Interleukin 1 production by the human monocyte cell line U937 requires a lymphokine induction signal distinct from interleukin 2 or interferons. AB - A soluble product from cloned human T lymphocytes is capable of stimulating U937 cells, a line of human monocytes, to produce interleukin 1 (IL 1). We previously reported that U937 cells exposed to T lymphocyte-conditioned medium secrete mononuclear cell factor (MCF), which increases collagenase and prostaglandin E2 production by adherent rheumatoid synovial cells. Whereas structural and functional homologies between lymphocyte-activating factor (LAF, or IL 1) and MCF were described, previous attempts to measure LAF secretion by lymphokine stimulated U937 cells were unsuccessful. Although the crude supernatants of cultured U937 cells exposed to medium from lectin-stimulated peripheral blood or cloned T lymphocytes contained MCF activity, no LAF activity was detected. After these crude supernatants were chromatographed on Ultrogel AcA54, however, and the fractions were individually assayed for IL 1, MCF and LAF activities were coeluted with apparent m.w. approximately 14,000 to 23,000. The inability to detect LAF activity in the unfractionated medium was accounted for by an inhibitor of lymphocyte proliferation present in fractions of higher m.w. The T lymphocyte product that stimulated U937 cell maturation and monokine production was secreted in response to lectin-stimulation in a dose-dependent fashion. Although we have previously demonstrated that the hormone 1,25-dihydroxyvitamin D3 caused maturational changes in U937 cells, and other investigators have reported effects of alpha and gamma interferon, these changes are dissociable from IL 1 production. Thus, a distinct lymphocyte-derived signal, necessary for the production of IL 1 by U937 cells, can be identified and dissociated from other biologic products that cause "maturational" changes. The detection of LAF activity in U937 cell supernatants requires the removal of an inhibitor of lymphocyte proliferation. PMID- 2578048 TI - Interaction of monoclonal antibodies with MHC class I antigens on mouse spleen cells. II. Levels of expression of H-2K, H-2D, and H-2L in different mouse strains. AB - The numbers of MHC class I molecules expressed by spleen cells from various mouse strains were determined by using MHC-specific monoclonal antibodies and a radioactive binding assay. Although small differences were found to exist in some cases, our general conclusion is that different mice of the same strain, congenic mice of different haplotypes, and syngeneic mice of varying background all express similar numbers of class I antigens. B10.A mice (8 to 10 wk old), for example, express 5.3 X 10(4) Kk molecules/cell, 5.4 X 10(4) Dd molecules/cell, and 2.2 X 10(4) Ld molecules/cell. Some of the differences observed in class I antigen expression included: 1) the level of Kk expression increased to a small but significant extent with age in B10.A mice; 2) female B10.A mice expressed slightly higher amounts of Kk than male mice; and 3) B10.A(2R) and B10.A(4R) recombinant strains expressed elevated levels of K-end antigens and slightly decreased levels of D-end antigens when compared with the unrecombinant B10.A strain. In several strains, F1 mice express approximately 50% as many copies of each parental antigen as do the homozygous parents. B10 mice, which are negative for the L antigen, nevertheless express the same total number of D-end molecules as do B10.A mice. The data suggest that the levels of expression of MHC class I molecules are controlled by at least two factors: gene dosage and another factor(s) that gives rise to the small variations in class I antigen expression seen with age, sex, and strain, and to the low expression of Ld relative to Dd and Kk. PMID- 2578049 TI - Identification of epitopes associated with hCG and the beta hCG carboxyl terminus by monoclonal antibodies produced against a synthetic peptide. AB - We have produced a library of monoclonal antibodies directed against a 37-amino acid synthetic polypeptide analogous to the carboxyl terminus of hCG. Five antibodies, designated FB01, FB02, FB03, FB04, and FB00, were developed and analyzed with respect to affinity and specificity for epitopes on human chorionic gonadotropin (hCG) and beta hCG by enzyme-linked immunoabsorbent and radioimmunoassays (RIA). All monoclonal antibodies demonstrated low affinity constants (approximately 10(-7) liters/mol) compared with those obtained by immunization with native beta hCG. One antibody, namely FB00, bound only to the synthetic peptide, whereas all other monoclonal antibodies recognized either free native beta hCG or both beta hCG and HCG. Antibodies produced against the synthetic peptide did not cross-react with other glycoprotein hormones such as LH, TSH, and FSH. Characterization of the monoclonal antibody-binding sites revealed the presence of at least four separate and distinct epitopes on the last 35 amino acids of beta hCG. Indeed, one epitope recognized by FB01 is located between residues 109 and 118, whereas another antigenic region recognized by FB04 appears to be present on the 109-121 portion of the molecule near or at position 118. One additional antigenic site was localized between residues 118 and 136. Finally, FB00 recognized an epitope located on the last 10 amino acids (136-145) of beta hCG. With the use of such antibodies, two- and three-site monoclonal RIA were developed and employed to detect free beta hCG and hCG in sera of patients with choriocarcinoma. These assays may be useful in the detection of beta hCG- and hCG-producing tumors and subsequent monitoring of patients in response to surgery and/or chemotherapy. PMID- 2578050 TI - Normal function of CR1 on affected erythrocytes of patients with paroxysmal nocturnal hemoglobinuria. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia in which affected erythrocytes (E) are abnormally sensitive to lysis by autologous complement. Affected E from patients with PNH (PNH-E) are deficient in an E membrane regulatory protein of complement, decay-accelerating factor (DAF). Because a functional defect in a second membrane regulatory protein of complement, CR1 (C3b receptor), has also been hypothesized, severely affected PNH E (type III PNH-E) were tested for abnormalities in CR1 by four methods. E from two patients with 100% type III PNH-E had 3201 and 6783 sites per cell for binding of 125I-labeled rabbit polyclonal F(ab')2 anti-CR1. These values fall within the normal range of CR1 antigenic sites per cell (1267 to 7915, mean = 5,014 +/- 155 SEM) established by assaying the E from 113 healthy donors. The Ka of CR1 on type III PNH-E for 125I-labeled C3b dimer was 2.06 X 10(7) M-1, and the Ka values for the binding of the same ligand to the E from two healthy individuals were 2.45 X 10(7) M-1 and 1.58 X 10(7) M-1. In an assay designed to measure the capacity of human E (Eh) to accelerate the decay of the classical C3 convertase deposited on 1 X 10(7) bystander sheep E (EAC1gp,4bh,2agp), the half life (t 1/2) of this convertase was diminished from 18.1 min (range 15.2 to 22.9) to 8.1 min (range 7.4 to 8.5) by the addition of 1 X 10(7) normal Eh, to 6.2 min by 100% type III PNH-E, and to 7.5 min by Eh pretreated with an IgG fraction of human antiserum directed against the D antigen of the Rh system. In contrast, Eh (t 1/2 = 7.4) pretreated with a saturating dose of F(ab')2 anti-CR1, and CR1 deficient Eh (less than 10 CR1 molecules/E) from a patient with systemic lupus erythematosus, showed a loss of convertase decay-accelerating capacity to t 1/2 = 11.6 and t 1/2 = 12.4, respectively. Type III PNH-E pretreated with anti-CR1 demonstrated a total loss of their decay-accelerating capacity (t 1/2 = 19.9). In an assay of I cofactor activity, soluble C3b was rapidly converted to iC3b by purified I plus Eh or type III PNH-E, whereas CR1-deficient Eh exhibited less than 5% the I cofactor activity of normal Eh.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2578051 TI - Monoclonal antibodies against human mast cell tryptase demonstrate shared antigenic sites on subunits of tryptase and selective localization of the enzyme to mast cells. AB - Two murine monoclonal antibodies were prepared against tryptase, the major neutral protease and protein component of human mast cells. The antibodies were termed G5 (IgG2B-kappa) and H4 (IgG1-kappa). They were specific for tryptase by an enzyme-linked immunosorbent assay and an immunotransblot technique. The latter procedure showed that H4 and G5 each bind to the 35,000 and 37,000 m.w. subunits of tryptase, indicating immunologic cross-reactivity between the subunits. The monoclonal antibodies reacted only with tryptase subunits in an extract of dispersed lung cells. By immunofluorescence microscopy, tryptase was further identified to be present only in cytoplasmic granules of Alcian Blue-stained mast cells in dispersed pulmonary cell preparations. No evidence for a mast cell subtype lacking tryptase was detected. In addition, a procedure for the purification of tryptase to homogeneity from dispersed pulmonary cells containing less than 10% mast cells was developed; this procedure involved high salt extraction, ammonium sulfate precipitation, and sequential chromatography with decyl-agarose, DEAE-agarose, and heparin-agarose. The procedure resulted in a higher yield even with less pure starting material than reported previously. Tryptase is a selective marker for mast cells in dispersed pulmonary cells, and can be detected with specific anti-tryptase antibodies. PMID- 2578052 TI - Morphologic and immunologic characterization of human basophils developed in cultures of cord blood mononuclear cells. AB - Selective growth of human basophilic granulocytes was obtained in suspension cultures of mononuclear cells from umbilical cord blood. Approximately 50 to 80% of nonadherent cells recovered from 2- to 3-wk-old cultures contained metachromatic granules, and these cells were identified as human basophilic granulocytes by electron microscopy. Histamine content of cultured human basophils was comparable to that in peripheral blood basophils. Cultured basophils bear 2.7 to 3.7 X 10(5) IgE receptors per cell that bind both human IgE and rodent IgE with comparable affinity. Average equilibrium constants of the receptors for human IgE and mouse IgE were 2.56 +/- 0.88 X 10(9) M-1 and 1.85 +/- 0.86 X 10(9) M-1, respectively. The cell-surface component of the IgE receptors on cultured basophils has a m.w. of 64,000. Cultured basophils could be passively sensitized with human IgE and mouse IgE monoclonal antibody, and sensitized basophils released characteristic cytoplasmic granules and both histamine and arachidonate upon challenge with either anti-human IgE or antigen. Incubation of cultured basophils with ionophore A23187 or F-Met-Leu-Phe resulted in histamine release. However, compound 48/80 failed to induce histamine release from the cells. PMID- 2578054 TI - Characterization of the effects of phorbol esters on rat mast cell secretion. AB - When applied to the skin, phorbol esters (PEs) elicit signs of acute inflammation, suggesting they may induce the release of mediators from mast cells. Therefore, we have studied the effects of PEs on purified rat peritoneal and thoracic mast cells both alone and in conjunction with the calcium ionophore, A23187, and various other secretagogues that interact with immunoglobulin E (e.g., anti-IgE and Con A) or other cell surface receptors, e.g., somatostatin and compd 48/80. PEs alone caused little or no release of histamine. However, the PE 12-O-tetradecanoylphorbol-13-acetate (TPA, 10 ng/ml) tremendously potentiated release induced by the calcium ionophore A23187, reducing the EC50 for A23187 from 832 ng/ml to 56 ng/ml. In the presence of suboptimal A23187 (50 ng/ml), only active tumor promoting PEs elicited histamine release. The EC50 values of the various active PEs were: TPA 5 ng/ml; 4 beta-PDD, 83 ng/ml; and 4-O-methyl-TPA, 807 ng/ml, with maximal histamine release ranging from 54 to 80%. TPA synergistically enhanced stimulation of histamine release by anti-IgE and Con A over the entire concentration-response range. In contrast, this synergism was absent when cells were stimulated with somatostatin and compd 48/80. Phorbol esters may act by increasing the activity of a calcium/phospholipid-dependent protein kinase (Ca/PL-PK). Mast cells do have Ca/PL-PK activity, and TPA in the presence of suboptimal A23187 induces protein phosphorylation comparable with other secretagogues. These results suggest that in the purified mast cell, PE induced mediator release increases the sensitivity of release mechanisms for calcium, acts syngergistically with secretagogues interacting with IgE, and as suggested from structure-activity relationships, occurs via a specific mechanism of action perhaps involving the Ca/PL-PK. PMID- 2578053 TI - Complement- and IgE-mediated release of histamine from basophils in vitro. V. Differential effects of drugs modulating arachidonic acid metabolism. AB - Basophil degranulation probably plays a significant role in the pathogenesis of different hypersensitivity reactions. These cells can be stimulated to secrete lysosomal histamine in vitro in response to various secretagogues. We compared the effects of drugs, modulating arachidonic acid (AA) metabolism, on histamine release (HR) from human basophils stimulated by anti-IgE antibody or C5a anaphylatoxin. Leukocytes from normal donors were preincubated with drug for 15 min at 22 degrees C, followed by the addition of C5a or anti-IgE for 30 min at 37 degrees C. Bromophenacyl bromide, an inhibitor of AA formation by phospholipase, blocked the effects of C5a and anti-IgE (greater than or equal to 3.3 X 10(-6) M, p less than 0.05 and p less than 0.01, respectively). 3-Amino-1-(3 trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW755C, greater than or equal to 3.3 X 10(-5) M) and 5, 8, 11, 14-eicosatetraynoic acid (greater than or equal to 3.3 X 10(-4) M), known inhibitors of both cyclooxygenase (COX) and lipoxygenase (LPX) pathways of AA metabolism, blocked both C5a- and anti-IgE induced HR (p less than 0.01). Nordihydroguaiaretic acid, an inhibitor of LPX, decreased HR induced by anti-IgE (greater than or equal to 3.3 X 10(-6) M, p less than 0.01) and allergens, but reduced C5a-initiated HR only at a higher concentration (greater than or equal to 7 X 10(-5) M, p less than 0.01). Indomethacin (INDO), an inhibitor of COX, significantly reduced HR caused by C5a (greater than or equal to 3.3 X 10(-8) M, p less than 0.01) and its degradation product C5adesArg, but had no effect or caused slight enhancement of HR initiated by anti-IgE. We confirmed that INDO augments allergen-induced HR. Our findings suggest that there are basic differences in the regulation of C5a- and IgE mediated basophil degranulation. PMID- 2578055 TI - Antiprotozoan activity of nonspecific cytotoxic cells (NCC) from the channel catfish (Ictalurus punctatus). AB - Nonspecific cytotoxic cells (NCC) obtained from channel catfish (Ictalurus punctatus) kill Tetrahymena pyriformis, an opportunistic parasite in fish. Based upon this fact, a new mechanism for nonspecific cellular anti-parasitic immunity in fish is proposed. Optimum in vitro conditions for NCC killing of deciliated T. pyriformis were first obtained. Lysis of T. pyriformis by NCC occurred by 10 hr of cocultivation of effector and target cells. During this time period, 50 to 60% cytotoxicity occurred. Fish anti-T. pyriformis serum enhanced NCC killing of T. pyriformis either by prolonging immobilization (after the cilia regeneration period) or by delaying cilia regeneration. Shared antigenic determinants between T. pyriformis, Ichthyophthirius multifiliis, and NC-37 target cells were demonstrated by binding-depletion experiments. For these studies, NCC were depleted from anterior kidney cells (the hemopoetic organ in fish) by preincubating formalin-treated T. pyriformis, I. multifiliis, or viable NC-37 target cells with NCC for 3 hr. Conjugates of effector and target cells were removed by overlaying on fetal bovine serum. Unconjugated fish anterior kidney cells were tested for cytotoxic activity against NC-37 or T. pyriformis target cells. Cold target inhibition experiments by using a 4-hr 51chromium cytotoxicity assay also demonstrated these shared antigenic determinants. Target-specific antisera, used to mediate the killing of T. pyriformis by NCC, were required only for immobilizing the targets, and did not function in an antibody-dependent cell mediated (ADCC)-like mechanism. Scanning electron micrographs of NCC-T. pyriformis conjugates additionally demonstrated NCC binding to both cilia and cell surface determinants. PMID- 2578056 TI - Amino acid sequence of porcine myelin basic protein. AB - The myelin basic protein (BP) of pig brain was cleaved into its constituent tryptic peptides and the amino acid composition of each was determined. Those tryptic peptides that had not been sequenced previously were cleaved with dipeptidyl peptidases and the resulting dipeptides were trimethylsilated, separated by gas chromatography, and identified by mass spectrometry. Carboxypeptidases B and Y were used to establish the COOH-terminal sequences of some of the tryptic peptides; one tryptic peptide (sequence 76-92) was cleaved with thermolysin and the thermolytic peptides were analyzed. From the results of the present study together with those reported previously, it has been possible to determine the complete amino acid sequence of the protein. The protein consists of 172 residues and has a theoretical molecular weight of 18,604. Its amino acid sequence is identical with that reported for the homologous bovine protein with the following exceptions: Ser replaces (bovine) Ala2; His-Gly is inserted between Arg9 and Ser10; Ala replaces Ser45; His and Gly replace Gly76 and His77, respectively; Pro replaces Ser131 and Ser135; Ala is inserted between Gly142 and His143; and Gln replaces His143. PMID- 2578057 TI - Chromatin proteins share antigenic determinants with neurofilaments. AB - Antigenic determinants common to distinct proteins may be unambiguously identified by the use of monoclonal antibodies. Some monoclonal antibodies to mammalian neurofilaments have recently been shown to cross-react with the neurofibrillary tangles found at high density in the brains of senile dements with Alzheimers disease (SDAT). Here, we show that these antibodies also cross react with chromatin proteins, including the linker histones H1 and H1(0). Elevated levels of histone H1(0) have also been reported in SDAT brains. PMID- 2578058 TI - Protein turnover in brain of the rat fetus. AB - Protein synthesis in vivo was studied in whole brain of rat fetuses using continuous intravenous infusion of L-[U-14C]tyrosine into unrestrained pregnant rats at 19 and 21 days gestation. Protein degradation (KD) was calculated by subtracting fractional growth rate of brain protein (KG) from the fractional synthesis rate (KS). KS was high at both gestational ages (0.42 +/- 0.03 days-1 at day 19, 0.47 +/- 0.029 days-1 at 21 days), comparable to values previously reported for newborn rat cerebral hemispheres, and threefold higher than is seen in adult animals. KD was similar at both 19 and 21 days gestation (0.19-0.24) and lower than that reported in neonatal rat brain using similar techniques. Protein accretion during the most rapid phase of brain growth (fetus) is accomplished by similar rates of protein synthesis, but decreased rates of degradation when compared with a slower growth phase (newborn). KD in the brain of the rapidly growing fetus is slightly higher than in adult cerebral hemispheres. PMID- 2578059 TI - Comparative ontogenesis of brain tryptamine, serotonin, and tryptophan. AB - The pattern of ontogenetic development of tryptophan (TP), tryptamine (T), indole 3-acetic acid (IAA), 5-hydroxytryptamine (5-HT; serotonin), and 5-hydroxyindole-3 acetic acid (5-HIAA) in the brains of rats aged 1-45 days is presented. Analysis of the five components in each brain allows the calculation of the acid/amine and amine/amino acid ratios. These metabolic indexes are a useful tool to study and compare the metabolic origins and fates of both amines. The ontogenetic patterns of TP, T, and IAA are very similar, especially during the first week postpartum. The highest and lowest levels found for T were 2.2 ng/g and 0.1 ng/g at the 1st and 5th day, respectively. The temporal relationship between the T/TP and IAA/T ratios suggests the existence of mechanisms protecting T against monoamine oxidase (MAO) which develop in parallel to synaptogenesis. Significant correlations were found between TP and IAA during the whole period studied and between TP and T during the first week after birth. The 5-HT peak found during the first postpartum week could be due to a non-neuronal pool of 5-HT protected against MAO and possibly contained in mast cells. Preliminary determinations on leptomeningeal membranes suggest the existence of such a pool. PMID- 2578060 TI - Reversible dihydropyridine isothiocyanate binding to brain calcium channels. AB - Voltage-dependent calcium channels from ileal smooth muscle can be affinity labeled with a [3H]dihydropyridine isothiocyanate radioligand. We examined the binding of this agent to brain membranes, to compare the properties of calcium channel drug binding sites in brain with those previously described in ileum. In brain, the [3H]dihydropyridine isothiocyanate labels sites that correspond in number and pharmacologic characteristics to binding sites for the classic calcium entry blocker, [3H]nitrendipine. However, in contrast to the covalent nature of dihydropyridine isothiocyanate binding in ileum, brain calcium channels are labeled reversibly. This difference in binding properties may reflect structural variations in voltage-dependent calcium channels in different tissues. PMID- 2578061 TI - Free and conjugated amines in human lumbar cerebrospinal fluid. AB - Significant amounts of acid-hydrolyzable conjugates of 3,4 dihydroxyphenylethylamine, norepinephrine, and 5-hydroxytryptamine were detected in lumbar CSF from 22 awake unpremedicated healthy individuals. In the CSF samples, the amounts of conjugated amines almost always exceeded the amounts of free amines, but were less than the amounts of the acid metabolites 3,4 dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid. PMID- 2578062 TI - Sidedness of phosphatidylcholine-synthesizing enzymes in rat brain microsomal vesicles. AB - The sidedness of CDP-choline:1,2-diradylglycerol choline phosphotransferase (EC 2.7.8.2) and of the choline base-exchange activity has been studied in rat brain microsomal vesicles. Proteases (trypsin and pronase) and mercury-dextran have been used as reagents for membrane surface components. All of them could inactivate both enzymes to a good extent, without affecting the morphology or the permeability to sucrose of the vesicles. It is therefore concluded that CDP choline:1,2-diradylglycerol choline phosphotransferase and the choline base exchange activity are localized on the outer surface of rat brain microsomal vesicles. PMID- 2578063 TI - Dopamine, serotonin, and acid metabolites in brain regions from the developing offspring of ethanol-treated rats. AB - Female rats were pair-fed control or ethanol liquid diets on a chronic basis prior to parturition. Six brain regions (hypothalamus, cerebellum, brain stem, cortex, corpus striatum, and hippocampus) were dissected from 19- and 35-day-old rat offspring for the determination of dopamine (DA), serotonin (5-HT), 3,4 dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA). DA, 5-HT, and the acid metabolites were separated simultaneously by reverse-phase HPLC and were quantitated using electrochemical detection. Between 19 and 35 days of age in control rats we observed an increase in the concentration of 5-HT and 5-HIAA in the corpus striatum and hippocampus and a decrease in these compounds in the cerebellum. In addition, there was a development-related decrease of 5-HIAA in the hypothalamus and an increase in the brain stem. During the same age period the concentration of dopamine increased in the hypothalamus and corpus striatum. There was also a development-related decrease in the concentration of DOPAC in the corpus striatum and an increase in the cortex as well as a decrease in HVA in the cerebellum and cortex. In comparison to age-matched control animals the 19- and 35-day-old offspring of ethanol-treated rats had a lower concentration of 5-HT and/or 5-HIAA in the cortex, cerebellum, and brainstem. In addition the 35-day-old offspring of ethanol-treated rats exhibited a decrease in DA and HVA in the cortex. The results of the present study suggest that in utero ethanol exposure affects both the serotonergic and dopaminergic systems in brain. PMID- 2578064 TI - Evaluation of postoperative intratumoral injection of bleomycin for craniopharyngioma in children. AB - Total excision is the treatment of choice in preventing the relapse of craniopharyngioma, but for tumors involving an extensive area, it is often associated with increased risks of complications. The efficacy of postoperative radiotherapy has not yet been established. The authors have performed minimal tumor excision followed by intensive injection of bleomycin into the remaining tumor as postoperative adjuvant therapy in seven children with craniopharyngioma. Long-term outcome in the children with cystic-type tumors containing little or no solid tissue has proven the regimen to be more advantageous than total excision. PMID- 2578065 TI - Immunotherapy in genitourinary neoplasia. PMID- 2578066 TI - Comparison of the effects of primary prostaglandins on isolated human urinary bladder. AB - The effects of primary prostaglandins (PGs) on the dome and trigone of the human urinary bladder were investigated in vitro. In the dome preparations, PGE1 (10( 9) to 10(-6) gm./ml.) showed a weak contractile effect, while PGE2 (10(-9) to 10( 6) gm./ml.) produced dose-dependent contractions. PGF2 alpha (10(-9) to 10(-6) gm./ml.) induced contractions greater than those induced by PGE1 and PGE2. In the trigone preparations, PGE1 (10(-9) to 10(-6) gm./ml.) had no effect, and PGE2 (10(-9) to 10(-6) gm./ml.) produced only a weak contractile response. PGF2 alpha (10(-9) to 10(-6) gm./ml.) showed a greater contractile potency than PGE2. Contractile responses of both preparations to PGE1, PGE2 and PGF2 alpha were not affected by pretreatments of atropine, hexamethonium and phentolamine. These results suggest that the order of potency of primary PGs to induce contractile responses is PGF2 alpha greater than PGE2 greater than PGE1 in both the dome and the trigone preparations, and that the contractile effects of PGE1, PGE2 and PGF2 alpha may not be mediated by activation of muscarinic, nicotinic or adrenergic alpha-receptors. PMID- 2578067 TI - Auto-injection of the corpus cavernosum with a vasoactive drug combination for vasculogenic impotence. AB - Intracavernous injection of papaverine hydrochloride with phentolamine mesylate rapidly produces transitory penile tumescence, which can be followed by erection and coitus provided there is sexual stimulation. Coital penetration was possible in 59 of 62 patients with impotence of divers etiologies (vascular, diabetic, iatrogenic and Peyronie's disease) who underwent injection and were sent home to attempt coitus. One patient had a prolonged erection that was treated successfully with aspiration of a corpus. When coitus was successful the patient was offered training in self-injection. With self-injection 18 patients have had satisfactory coitus without a noteworthy complication; 5 for more than 12 months. The long-term effects of intracavernous injections remain unknown. Intracavernous injection of vasoactive substances (chemical prosthesis) may become a useful alternative treatment. Administration should be restricted to urologists able to manage the possible complication of priapism. PMID- 2578068 TI - Mitogenic factors in prostatic tissue and expressed prostatic secretion. AB - Expressed prostatic secretions and extracts of benign prostatic hyperplasia tissue contain a polypeptide growth factor(s) that stimulates the uptake of tritium-labeled thymidine by cultured 3T3 fibroblasts. Mitogenic activity was present in expressed prostatic secretions and extracts of benign prostatic hyperplasia tissue. The apparent molecular weights of the mitogenic fractions were estimated to be 300,000, 150,000 and 60,000 daltons for prostatic tissue extracts, and 30,000 daltons for expressed prostatic secretions. Bioassays yielded a mean of 27 units of mitogenic activity per mg. protein in expressed prostatic secretions obtained from men with normal and enlarged prostate glands. There was no difference in bioassayable mitogenic activity in the expressed prostatic secretions from normal and benign prostatic hyperplasia samples but gel filtration studies revealed a high molecular weight component present only in samples from men with prostatic enlargement. A dialyzable low molecular weight inhibitor of fibroblast growth was found in the prostatic tissues and expressed prostatic secretions. We report the characterization studies and discuss the possible roles of growth factors in the pathogenesis of benign prostatic hyperplasia. PMID- 2578069 TI - Beta 2-microglobulin and the acquired immunodeficiency syndrome in a low incidence area. PMID- 2578070 TI - Magnetic resonance imaging of the prostate. AB - Twenty-two normal volunteers and 32 patients with either benign prostatic hypertrophy or prostatic carcinoma were examined by magnetic resonance imaging (MRI). The images were of high quality and clearly demonstrated the prostate gland and the surrounding anatomy but were of limited value in differentiating between benign and malignant prostatic disease. Using a specific pulse sequence, the authors were able to visualize what they believed to be the periprostatic venous plexus and suggest that the demonstration of this venous plexus may be of value in showing extraglandular spread of carcinoma of the prostate. PMID- 2578071 TI - Two distinct populations of calcium channels in a clonal line of pituitary cells. AB - The whole-cell variant of the patch clamp technique was used to study calcium channels in GH3 cells. Two distinct populations of calcium channels, first recognized from their closing kinetics, were observed. The slowly closing channels are activated in a relatively negative voltage range and are inactivated within 100 milliseconds. They conduct barium and calcium about equally well. The fast closing channels are activated at more positive voltages, are not inactivated during a 100-millisecond pulse, conduct barium in preference to calcium, and are activated slightly more rapidly than the slowly closing channels. PMID- 2578072 TI - Intraoperative localization of parathyroid glands using methylthionine chloride / tetramethylthionine chloride in secondary hyperparathyroidism. AB - Over an 18 month interval at the University of Louisville Affiliated Hospitals, 40 patients were evaluated in a nonrandomized prospective study to determine the value of methylthionine chloride / tetramethylthionine chloride (methylene blue- MB) as an aid for the rapid intraoperative identification of parathyroid hyperplasia of end-stage renal disease (ESRD). Patients assigned to the MB infusion subgroup had infusion of 1 per cent MB (5.5 milligrams per kilogram) over a time interval of 25 to 60 minutes (mean of 43.9) prior to anesthetic induction. A total of 159 glands were identified in both the control and MB infusion groups (3.98 glands per patient) of which the predominant histopathologic diagnosis on frozen section was chief cell hyperplasia (78.3 per cent). Of 91 hyperplastic glands submitted for analysis after subtotal parathyroidectomy in those in the MB infusion group, 82 glands (90.1 per cent) were observed to have positive staining with identifiable differentiation from surrounding tissues. Analyses of the correlation of the serum calcium value and probability of MB staining or its relation to serum intact parathyroid hormone (intact-PTH) values were not statistically significant (p greater than 0.05, correlation coefficient equals 0.149). Furthermore, no relationship existed between the glandular size (millimeter to the third power) and probability of MB staining (chi-square equals 1.750, p greater than 0.05) or between hyperplastic size and serum intact-PTH value (correlation coefficient equals 0.068). Conversely, analysis of MB gland staining with regard to intact PTH concentration disclosed 59 of 59 glands stained intensely with MB when intact-PTH concentration was not less than 700 picograms per milliliter (p less than 0.01). Non-staining of hyperplastic parathyroid tissue was observed in 28.1 per cent of glands submitted for histopathologic analysis in which preoperative intact PTH values were more than 699 picograms per milliliter. Time of operation was reduced from 119.0 +/- 47.53 minutes (mean +/- S.E.M.) in control patients to 92.1 +/- 20.12 minutes (mean +/- S.E.M.) for the MB infusion group (V per cent equals 21.85, p less than 0.01). Furthermore, this technique appears to have value in the detection of ectopically located parathyroid tissue as demonstrated by the in vivo staining of seven ectopic glands in six patients of the infused group. Complications were restricted to the patients in the MB infusion group (21.7 per cent) and included: pseudo-cyanosis in three; pain in the infusion site in two, wound hematoma in one patient, pancreatitis in one and angina in one.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2578073 TI - Esophagogastrectomy without thoracotomy for carcinoma of the cardia and lower part of the esophagus. AB - Between 1 October 1979 and 1 September 1983, 34 patients with 25 adenocarcinomas and nine squamous cell carcinomas of the cardia and lower part of the esophagus have been treated with resection of the celiac lymph nodes (metastasis in 83 per cent of the patients), the lesser curvature of the stomach, cardia and total esophagus without thoracotomy. There was transmural spread of the cancer in 88 per cent of the patients. The esophagus was replaced by a tube made from the greater curvature of the stomach, which was brought through the mediastinum and anastomosed to the cervical esophagus. There was a hospital mortality of 2.9 per cent and the median hospital stay was 15 days. Morbidity included seven anastomotic leaks which closed spontaneously, intrathoracic bleeding (one), secretion retention (six), transient hoarseness (12), persistent dysphagia (one) and transient dumping syndrome (four). No patient has complained of aspiration or reflux of gastric juices. Satisfactory long term relief of dysphagia was achieved in 94 per cent of the patients. There have been no recurrences of tumor at the site of the anastomosis. The one year survival rate is 70 per cent and the median survival time is 19 months. PMID- 2578074 TI - Primary lymphoma of the gastrointestinal tract. AB - Forty-six instances of gastrointestinal tract lymphoma are reviewed with attention to clinical features, diagnostic studies, surgical approach and adjuvant therapy. Gastrointestinal tract lymphoma may be present at any age in individuals with pain, abdominal mass or other abdominal findings, and all ulcers and other endoscopically accessible lesions require biopsy, without regard for roentgenologic or endoscopic appearance of benignity. Resection is recommended when cure is possible; adjunctive therapy is regarded as beneficial. There is a good prognosis for those patients surviving two to three years beyond diagnosis. PMID- 2578075 TI - Premature ventricular beats in a previously healthy child. AB - A 12-year-old girl presented to the emergency department with a chief complaint of left-sided chest pain. On physical examination she was noted to have an irregular pulse, and an electrocardiogram revealed 30 to 50 premature ventricular contractions per minute with periods of bigeminy. The patient was admitted to the intensive care unit and treated with antiarrhythmic medication without resolution of her premature ventricular contractions. A diagnostic workup, including echocardiogram, Holter monitoring, and exercise stress testing, was performed. It was determined that the cardiac dysrhythmia, consisting of unifocal premature ventricular contractions with a characteristic configuration on the electrocardiogram, was benign in nature and did not require antiarrhythmic therapy. PMID- 2578076 TI - Absence of a surface-connected canalicular system in bovine platelets. AB - Human platelets possess a surface-connected canalicular system (SCCS) which has been postulated to subserve endocytosis as well as secretion. Platelets of most animal species studied to date, including those of cattle, function similarly. However, ultrastructural analysis of freeze-fractured bovine platelets or thin sectioned bovine platelets treated with electron-dense tracers failed to delineate a SCCS. This observation may throw an entirely new light on the role of this organelle. PMID- 2578077 TI - William Withering and digitalis, 1785 to 1985. PMID- 2578078 TI - Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. AB - Combined hepatocellular-cholangiocarcinoma is a rare form of primary liver cancer showing features of both hepatocellular and biliary epithelial differentiation. In a review of 24 cases of this tumor, three histologic types were encountered. Four cases were Type I or "collision tumors," apparently a coincidental occurrence of both hepatocellular carcinoma and cholangiocarcinoma in the same patient. Twelve cases were Type II or "transitional tumors," in which there were areas of intermediate differentiation and an identifiable transition between hepatocellular carcinoma and cholangiocarcinoma. Eight cases were Type III or "fibrolamellar tumors" which resembled the fibrolamellar variant of hepatocellular carcinoma but which also contained mucin-producing pseudoglands. Type III tumors differ from other combined tumors, occurring at a younger age, in the absence of cirrhosis, and having a slightly longer survival. Immunohistochemical (immunoperoxidase) staining for intracellular antigens showed that alpha-fetoprotein is a fairly specific, although insensitive, marker of hepatocellular differentiation in primary liver cancers, being present in 50% of typical hepatocellular carcinomas and in hepatocellular areas in 29% of combined tumors, but in no cholangiocarcinomas or cholangiocellular areas of combined tumors. Keratin is a good marker of biliary epithelial differentiation, being found in 90% of cholangiocarcinomas and in 52% of combined hepatocellular cholangiocarcinomas, but in no hepatocellular carcinomas. Alpha-1-antitrypsin, fibrinogen, IgG, and carcinoembryonic antigen may be found in both hepatocellular carcinoma, cholangiocarcinoma, and in combined tumors; these antigens are therefore of limited use in differential diagnosis. PMID- 2578079 TI - Serum alpha-fetoprotein subfractions in patients with primary hepatoma or hepatic metastasis of gastric cancer. AB - Alpha-fetoprotein (AFP) subfractions were studied in 38 sera including 34 patients with primary hepatoma and 4 from patients with hepatic metastasis of gastric cancer. Fractionation of AFP was carried out by concanavalin A (Con A) or lentil lectin (LCH) crossed-line affinity immunoelectrophoresis. With use of Con A, fetal-liver-originated subfraction (peak a) was commonly found in both primary hepatoma and metastatic liver cancer, while yolk-sac-originated subfraction (peak b) was detected in 7 of 34 (20.6%) primary hepatomas and 4 of 4 (100%) metastatic liver cancers. With use of LCH, fetal-liver-originated subfractions (peaks A and/or C) were commonly found in both primary hepatoma and hepatic metastasis of gastric cancer, while yolk-sac-originated subfraction (peak B) was found only in metastatic liver cancer. These findings suggest that glycosylation of AFP in primary hepatoma differs from that in hepatic metastasis of gastric cancer. It is also suggested that AFP synthesized in hepatic cancers and fetal liver are differently glycosylated and AFP synthesis of hepatic malignancies are not always retrogenetically expressed, as in case of the fetal liver. Clinically, different patterns of AFP subfraction identified by Con A or LCH crossed-line affinity immunoelectrophoresis facilitate a differential diagnosis of primary hepatoma and hepatic metastasis of gastric cancer, in cases of elevated serum AFP levels. In the current study, attention was also given to the retrogenetic expression of AFP synthesis in hepatic metastasis of gastric cancer. PMID- 2578080 TI - Atypical fibroxanthoma distinguishable from spindle cell carcinoma in sarcoma like skin lesions. A clinicopathologic and immunohistochemical study of 21 cases. AB - A clinicopathologic study was done of 21 cutaneous, sarcoma-like lesions previously diagnosed as atypical fibroxanthoma, spindle cell carcinoma, or dermal sarcoma. These lesions were most commonly presented as a solitary, often ulcerated nodule, occurring on exposed skin of the face in the elderly or, occasionally, on roentgen-damaged or burnt skin of the head, leg, or hand. Microscopic features of the 21 lesions were, however, not alike, thereby implying that such sarcoma-like lesions had derived from heterogeneous origins. The immunohistochemical staining in a comparative study with two other cases of unequivocal spindle cell squamous carcinoma suggested that these lesions could be histogenetically divided into two different groups: (1) the major group of true atypical fibroxanthoma, consisting of 19 cases, and (2) the minor group of probable spindle cell squamous carcinoma, consisting of 2 cases. Despite a wide histologic spectrum and of heterogeneity of these lesions, there was a benign clinical course in the majority, due in part to the small size and superficial location of the lesions. PMID- 2578081 TI - Palliative and curative electrocoagulation for rectal cancer. Experience and results. AB - The 18-year experience with electrocoagulation of rectal cancer in 51 patients is reported. The "boiling" technique used in this study is described. Electrocoagulation for palliative purpose was carried out in 18 patients. One patient is alive without evidence of disease after 4 years. The remaining 17 patients died within 2 years. Electrocoagulation for cure was performed in 33 patients. In two patients abdominoperineal resection was needed for residual tumor. All cases were strictly followed, and none of the patients died of cancer. Recurrent tumor was never seen, and the crude 5-year survival was 71%. The authors describe the criteria for selection any patient should meet in order to be eligible for electrocoagulation with curative purpose and advocate caution in making the choice between radical and local surgery. PMID- 2578082 TI - Combined modality therapy for mediastinal Hodgkin's disease. Prognostic significance of constitutional symptoms and size of disease. AB - Combined modality therapy was used in an attempt to increase the complete remission rate and survival of previously untreated patients with Hodgkin's disease. MOPP (nitrogen mustard, vincristine, procabazine, prednisone) chemotherapy was followed by radiotherapy. The median duration of follow-up exceeded 5 years. Complete remissions were achieved in 63 of 71 patients (89%) with mediastinal masses. The actuarial survival of 10 years was 72% for patients with small mediastinal masses (mediastinal mass ratio less than 0.35) and 46% for patients with large mediastinal masses (P less than 0.05). The corresponding disease-free survival figures were 69% and 46%, respectively (P less than 0.05). A small mediastinal mass did not affect prognosis. Systemic symptoms especially affected the prognosis in patients with a large mediastinal mass, since in symptomatic patients the actuarial survival and freedom from relapse were 19%, whereas all asymptomatic patients survived without relapse. In patients with a small mediastinal mass, systemic symptoms had no significant effect on the actuarial survival or disease free survival. Age and stage did not affect the prognosis in patients with large mediastinal masses. It was concluded that MOPP chemotherapy followed by radiotherapy was an adequate treatment for asymptomatic patients with large mediastinal disease. However, in symptomatic patients with large mediastinal masses, this treatment was clearly inadequate. PMID- 2578083 TI - Enhancement of natural killer cell activity and 2-5A synthetase in operable breast cancer patients treated with polyadenylic; polyuridylic acid. AB - Treatment of operable breast cancer patients with a single injection of 60 mg poly(A); poly(U) (polyadenylic, polyuridylic acid) resulted in an enhancement of natural killer (NK) cell cytotoxicity against human myeloid K562 target cells. Furthermore, the level of 2-5A synthetase in peripheral blood lymphocytes of such patients was increased after the treatment. Both of these effects, measured 24 and 48 hours after the injection of poly(A); poly(U), were statistically significant compared to their respective levels before the treatment. These events, therefore, may be used as markers to monitor the immediate response of patients toward treatment with this synthetic double-stranded RNA. PMID- 2578084 TI - Immunoperoxidase study on adenomatoid tumor of the epididymis using anti mesothelial cell serum. AB - The mesothelial origin of epididymal adenomatoid tumor is supported by the current study for the presence of mesothelial antigen in the tumor cells. By an indirect immunoperoxidase technique, anti-mesothelial cell serum showed positive cytoplasmic staining in five of the six adenomatoid tumors studied. Previous findings of the presence of strong cytoplasmic keratin and the absence of carcinoembryonic antigen and Factor VIII-related antigen in these tumor cells are also confirmed by this study. PMID- 2578086 TI - Serum albumin in Hodgkin's disease. AB - Serum albumin levels were measured by electrophoresis in 552 evaluable patients with Hodgkin's disease. Determinations were made on all patients at onset, on 224 after induction therapy and on 78 in relapse after remissions of variable length. At onset a discrete hypoalbuminemia was evident, inversely related to stage and more marked in symptomatic cases and elder patients. Little or no differences in albumin levels were found with relation to histologic subtypes, sex and presence of weight loss or hepatic damage. Posttherapeutic normalization of serum albumin occurred only after achievement of complete remission and failed after partial remission, while a new clear decrease became evident in relapse. On the basis of 799 albumin measurements during active disease and in remission, the albumin/alpha 2-globulin ratio demonstrated a clear and useful clinical advantage over either albumin or alpha 2-globulin fractions alone as indicator of active disease and relapse. If defective synthesis is the most accepted mechanism for hypoalbuminemia in Hodgkin's disease, these results suggest a casual factor somehow related to the tumoral mass. PMID- 2578085 TI - Androgen receptor binding activity in human prostate cancer. AB - Androgen binding (cytosol and nucleus) was measured in tissue obtained from 223 untreated patients with proven prostate cancer (199 primary tumor, 24 malignant lymph nodes), 19 patients with hormone refractory cancer, and 46 patients with benign prostatic hyperplasia (BPH). The mean binding in both the cytosol and nucleus was significantly higher for patients with cancer than for those with BPH. Binding appeared to correlate with tumor stage. Androgen binding in malignant nodes can differ from that in the primary tissue and can vary from node to node in the same patient. Results obtained from an assay using a single saturating concentration of R1881 correlated well with those calculated from a full six-point Scatchard analysis when an adequate amount (500 mg) of tissue was available. However, binding results obtained from a single-point analysis performed on needle biopsy specimens (about 50 mg) obtained before complete surgical removal of the prostate correlated poorly with those derived from a full six-point analysis performed on tissue (500-1000 mg) removed from the center of the malignancy. Androgen binding in nuclear extracts of histologically benign tissue adjacent to the malignancy was significantly higher than in nuclear extracts of BPH tissue. Cytosolic androgen binding in tissue removed from patients who were refractory to hormonal therapy was higher than in tissue from untreated cancer patients. The binding of estradiol by extracts of benign and malignant prostate tissue was low or absent and, thus, did not appear to be a significant phenomenon. PMID- 2578087 TI - Clinically occult bladder cancer diagnosis. Trial using ultraviolet cystoscopy. AB - Ultraviolet cystoscopy was used to demonstrate flat cancerous and precancerous bladder lesions by two techniques based on different principles: the loss of epithelium blood group antigenic expression using immunofluorescence reaction, and submucosa neoangiogenesis after fluorescein intravenous injection. The results obtained with these two techniques were disappointing, but do not preclude the use of ultraviolet cystoscopy in this type of study. PMID- 2578088 TI - The histopathology of bleeding from polyps and carcinomas of the large intestine. AB - Carcinomas, adenomas and nonneoplastic polyps of the large intestine were examined histopathologically for evidence of recent and old hemorrhage. Three percent of the carcinomas lacked evidence of hemorrhage, as did 7% of the adenomas. Fifty percent of hyperplastic polyps were negative for hemorrhage, but 23% had considerable hemorrhage or hemosiderin. These findings may have a bearing on the results in fecal occult blood testing for the detection of cancer. Carcinomas bleed mainly from erosions on their luminal surface, but adenomas rarely show this feature. Twisting and bending of polyps, leading to fracture of fronds, and vascular obstruction, with passive congestion and stromal hemorrhage, appear to be the main sources of bleeding in polyps. Adenomas on the left side of the large intestine showed greater evidence of bleeding than did lesions on the right, but carcinomas did not show this relationship. Factors correlated with more severe hemorrhage were size, pedunculation, and villous growth of adenomas; for carcinomas, they were size, lack of mucin content, and lower differentiation. The age and sex of the patient and the extent of spread of carcinomas did not correlate with hemorrhage. PMID- 2578089 TI - Argyrophilic prostatic carcinoma. Case report with literature review on prostatic carcinoid and "carcinoid-like" prostatic carcinoma. AB - An unusual prostatic neoplasm characterized by a carcinoid-like light microscopic pattern together with argyrophilia of tumor cells is described. Immunoperoxidase stain for prostatic specific antigen, however, was positive, indicating that this neoplasm was an argyrophilic prostatic carcinoma. Although the clinical significance of a carcinoid-like pattern and/or argyrophilia in prostatic carcinoma is currently unknown, pathologic recognition of these features is of paramount importance because prostatic carcinoma with these features has to be distinguished from true primary prostatic carcinoid tumor or, in areas of metastasis, from metastatic carcinoid originating from other sites such as the gastrointestinal or respiratory tracts. The value of the immunoperoxidase technique for prostatic specific antigen as well as prostatic acid phosphatase in this differentiation is stressed. PMID- 2578090 TI - Amplified sequences from chromosome 15, including centromeres, nucleolar organizer regions, and centromeric heterochromatin, in homogeneously staining regions in the human melanoma cell line MeWo. AB - Homogeneously staining regions (HSRs) in the human melanoma cell line, MeWo, are located on an X and a der(15) chromosome. These regions are homogeneously stained with quinacrine fluorescence, but stain differentially with conventional Giemsa, G-banding, C-banding, and distamycin A/4',6-diamidino-2-phenylindole. There are five and six blocks of positively staining material on the X and der(15) HSRs, respectively. Hybridization in situ with a cloned repetitive Kpn I family member has confirmed the amplification of this sequence along the HSRs. With silver staining of the nucleolar organizer regions (NORs) there appear to be three very strong and two weaker pairs of NORs along the HSR of the X chromosome and four strong and one weaker pair on that of the der(15) chromosome. There was little NOR staining on the normal acrocentric chromosomes in these cells, suggesting preferential transcription of the NORs in the HSRs. Centromere-dot staining revealed a distribution of multiple centromeres similar to the NORs along the two HSRs. These data suggest that a unit composed of the short arm and centromere of chromosome #15 has been amplified and that the HSR present on the X chromosome probably arose by a translocation from chromosome #15. PMID- 2578092 TI - Mechanism of resistance of a variant of P388 leukemia to L-(alpha S,5S)-alpha amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin). AB - Acivicin [L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid; NSC 163501] is a fermentation-derived amino acid antibiotic antagonistic to L glutamine which exhibits potent oncolytic properties. We have developed a variant of P388 leukemia resistant to acivicin (P388/ACIA) and compared its properties with those of the parent line (P388/S). An examination of the enzymes utilizing L glutamine revealed that the basal specific activities of L-asparagine synthetase and L-glutaminase were 1-to 3-fold higher in the parent line. The activities of carbamoyl phosphate synthetase II, L-asparagine synthetase, formylglycinamide ribonucleotide amidotransferase, and guanosine monophosphate synthetase were about equally inhibited in the two cell lines, while there was a partial inhibition of 5-phosphoribosyl-1-pyrophosphate amidotransferase, fructose-6 phosphate amidotransferase, and L-glutaminase activities, found only in the sensitive line. Cytidine triphosphate synthetase activity was not inhibited in either line. There was no difference in the dose response or restitution of L glutamine utilizing enzyme activities between the two lines. Acivicin treatment produced a 2- to 3-fold augmentation of the L-glutamine pools only in the sensitive line. Drug injection induced increased 5-phosphoribosyl-1-pyrophosphate levels in both lines. Acivicin perturbed guanosine nucleotide pools only in the sensitive line, indicating that the primary mechanism of action of acivicin in P388 leukemia may be directed at guanosine monophosphate synthetase. Transport studies demonstrated a restricted uptake of acivicin by the resistant cells. These studies suggest that the transport of acivicin and L-glutamine plays an important role in determining the sensitivity or resistance to acivicin in these tumors. PMID- 2578091 TI - Disposition and metabolism of aniline in Fischer 344 rats and C57BL/6 X C3H F1 mice. AB - We examined the metabolism and disposition of aniline, which induces spleen hemangiosarcomas in rats but no tumors in mice, in normal and predosed Fischer 344 rats, and C57BL/6 X C3H F1 mice administered low (50 and 100 mg/kg, respectively) or high (250 and 500 mg/kg, respectively) doses. Of 11 tissues examined, the highest levels of binding of [14C]aniline to DNA were in the kidney, large intestine, and spleen of high-dose rats that had received prior dosing; these tissues had covalent binding indices of 14.2, 4.3, and 3.7 mumol/mol nucleotides/dose, respectively. Protein and RNA were the major macromolecular targets for binding of radioactivity from [14C]aniline. Relative to controls, most tissues from predosed mice (low dose and high dose) showed less binding to protein and RNA; but for most tissues from predosed rats administered 50-mg/kg doses of [14C]aniline, there was more extensive binding. Also relative to controls, binding of radioactivity in the spleen of predosed rats given [14C]aniline (50 mg/kg) was 148% greater for protein and 302% greater for RNA. For rats administered 250 mg of [14C]aniline per kg, however, there were no outstanding differences in binding to RNA and protein between normal and predosed animals. The profiles of urinary metabolites produced by rats and mice were not appreciably different in animals predosed with aniline. For rats, however, the profiles were different for the low and high doses, suggesting that the main metabolic pathway was saturated at the higher dose. p-Acetamidophenyl sulfate represented over 70% of the total radioactivity recovered from the urine of rats dosed with 50 mg of aniline per kg but only 30% in the urine of those dosed with 250 mg/kg. The urine of the high-dose rats contained greater percentages of p aminophenyl sulfate, p-acetamidophenyl glucuronide, and unconjugated metabolites. In mouse urine, p-acetamidophenyl glucuronide, representing 29 to 32% of the total radioactivity, was the major metabolite. Nevertheless, mice produced more ortho derivatives than did rats, for in acid-treated urine, the ratio of p- to o aminophenol was 8.1 for rats and 1.6 for mice. Predosing of rats and mice did not change the kinetic values for liver aniline p-hydroxylase or N-hydroxylase but increased the amount of mouse liver cytochrome P-450 from 0.231 to 0.491 nmol/mg protein. For p-hydroxylase of rat liver, the apparent Km value was higher, and the apparent Vmax value lower than in mouse liver. Kinetic values for rat and mouse N-hydroxylase were similar.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2578093 TI - Enhancement of mitomycin C cytotoxicity to hypoxic tumor cells by dicoumarol in vivo and in vitro. AB - Previous work by our laboratories demonstrated that dicoumarol can increase the enzymatic activation of mitomycin C (MC) to alkylating species by tumor cell sonicates under hypoxic conditions. To determine whether this increased generation of reactive metabolites would result in increased cytotoxicity, we examined the effect of this combination on the viability of EMT6 cells treated in vitro under hypoxic and oxygenated conditions. Dicoumarol increased the cytotoxicity of MC to these neoplastic cells under hypoxic conditions and decreased the toxicity of the antibiotic to aerobic cells. These findings suggested that dicoumarol might enhance the toxicity of MC to the hypoxic cells of solid tumors, without increasing the toxic side effects of the antibiotic to the host. Treatment of EMT6 tumor-bearing animals with both dicoumarol and MC significantly decreased the survival of the radioresistant hypoxic tumor cells from that obtained with MC alone. In contrast, the leukopenia produced by the antibiotic was not exacerbated by the addition of dicoumarol. These results suggest that a treatment regimen combining dicoumarol and MC might be a useful adjunct to radiation therapy for the eradication of the radioresistant hypoxic cells in solid tumors. PMID- 2578094 TI - Prevention of methotrexate cytotoxicity by asparaginase inhibition of methotrexate polyglutamate formation. AB - Escherichia coli asparaginase (Asnase) pretreatment of Asnase-sensitive L5178Y cells in vitro is thought to antagonize methotrexate (MTX) cytotoxicity through nonspecific inhibition of protein synthesis and MTX uptake. We have reexamined the mechanism of this interaction in view of recent data demonstrating the importance of MTX metabolism to polyglutamate derivatives (MTXPGs) in the cytotoxic effects of the antifolate. After a 3-hr exposure to 0.5 microM MTX, 67% of intracellular drug was in the form of MTXPGs containing a total of 2 to 5 glutamyl residues (MTX-Glu2-5), and cloning efficiency in drug-free medium was only 7% of untreated control. After a 3-hr pretreatment with E. coli Asnase (0.1 unit/ml), [3H]thymidine incorporation dropped by 29%, MTXPG formation during subsequent MTX exposure decreased by more than one-half (MTX-Glu2 unchanged; MTX Glu3 and 4 decreased to 51.7 and 18.5% of levels achieved in cells not pretreated with Asnase; no MTX-Glu5 formed), and cloning efficiency increased to 71% of untreated control. This effect was not due to decreased MTX uptake into L5178Y cells or to decreased intracellular free L-glutamate or L-glutamine levels. A 3 hr exposure of L5178Y cells to media lacking L-isoleucine, an essential amino acid for cell growth, prior to MTX exposure inhibited [3H]thymidine incorporation by 37%, decreased subsequent MTXPG formation by 62%, and increased subsequent cloning in drug-free medium to control levels. Decreased MTXPG formation was responsible for the prevention of MTX cytotoxicity seen after both pretreatments. Unmetabolized MTX rapidly left L5178Y cells after removal of extracellular MTX. Consequently, lower levels of unbound intracellular drug, a prerequisite of drug activity, were maintained in pretreated than in control cells after passage in drug-free medium. Asnase pretreatment protects L5178Y cells from the cytotoxic effects of MTX, possibly through inhibition of cell growth which nonspecifically decreases MTXPG formation. PMID- 2578095 TI - Demonstration of kallikrein in a rat pancreatic acinar cell carcinoma. AB - Kallikrein was identified immunohistochemically and biochemically in a transplantable pancreatic acinar cell carcinoma of the rat. The concentration of immunoreactive kallikrein in tumor homogenates was the same as in the pancreas. Kallikrein in tumor cells exists as a proenzyme and is released into blood in high concentrations. The impact of the presence of a kallikrein-producing tumor on other kallikrein-containing organs and other possibly interrelated systems was investigated. The concentration of kallikrein in the submandibular gland and pancreas of host rats was not significantly different from that of control rats. Urinary kallikrein secretion was significantly increased, although this may be a result of the high plasma glandular kallikrein concentration combined with kidney damage. The plasma concentration of kininogen, kininase, and renin was not significantly different from control rats. Rats with tumor had significantly lower blood pressure than did control animals, and blood pressure was inversely related to the concentration of glandular kallikrein in plasma. However, it was not proven that the low blood pressure was due to the high concentration of kallikrein. Nephrectomized tumor rats gave a smaller hypotensive response to kininase inhibition than was expected from their high concentration of circulating kallikrein. This may be explained by the absence of the "free kallikrein" fraction in plasma of host rats. PMID- 2578097 TI - Expression of the c-myb oncogene in human small cell lung carcinoma. AB - We have found that the oncogene c-myb is differentially expressed in human lung cancer cell lines and that myb-homologous RNA can be detected only in small cell lung cancer (SCLC) cell lines. Polyadenylic acid-RNA from 13 established cell lines was examined by Northern blotting for its ability to hybridize to a radiolabeled v-myb probe. A 3.5-kilobase RNA transcript homologous to v-myb is present in four of four lines of classic SCLC and in three of four SCLC variant lines but not in five of five non-small cell lung cancer lines tested. This transcript is the same size as that found in the immature myeloid cell lines KG1, but the amount of RNA is only about 10% of that in the KG1 line. A second transcript hybridizing to v-myb, 2.4 kilobases in size, is also present in the variant SCLC lines and the COLO 320 line, all of which have amplification of the c-myc gene and markedly increased c-myc messenger RNA. The presence of myb transcripts in SCLC suggests that the myb gene may have a specific role in the initiation or maintenance of an important human epithelial tumor. PMID- 2578096 TI - Generation and immunohistological characterization of human monoclonal antibodies to mammary carcinoma cells. AB - The purpose of this study was to identify human antibodies generated against autologous breast tumor cells by the host's immune response. Accordingly, lymphocytes from lymph nodes of seven different patients with metastatic breast carcinomas were immortalized by fusing them with a nonsecreting variant of murine myeloma cells. The screening for binding of antibodies to tumor cells was performed by indirect immunoperoxidase staining of paraffin-embedded tissue sections of the autologous tumor. The selected hybrid cells, after being cloned three times, were stable for the secretion of immunoglobulins for over 2 years. A total of 81 human immunoglobulin-producing clones was obtained from an initial 595 wells with hybrid growth. Nine of these clones produced immunoglobulin M, none of which showed detectable binding to tissue antigens in breast. Seventy-two clones produced immunoglobulin G monoclonal antibodies, and 15 of these showed preferential binding to breast carcinoma cells. Three of these immunoglobulin G monoclonal antibodies were subjected to detailed immunohistological evaluations. Using these antibodies at concentrations ranging from 10 to 100 ng/tissue section, the morphologically normal mammary epithelial cells could be discriminated from their malignant counterparts. The antibodies showed diffuse staining of cytoplasmic components in the malignant counterparts. Under these conditions, lymphocytes, erythrocytes, and stromal cells in breast tissues were unstained. The antibodies showed variable reactivity with malignant epithelial cells of colon and stomach, and with normal epithelial cells lining the renal tubules and sebaceous glands in skin. Antigenic heterogeneity of malignant mammary epithelial cells was revealed. The antibodies may have value in the characterization of tumor-associated antigens responsible for inducing autologous immune responses. PMID- 2578098 TI - Characterization of the placental alkaline phosphatase-like (Nagao) isozyme on the surface of A431 human epidermoid carcinoma cells. AB - A431 human epidermoid carcinoma cells monophenotypically express the placental alkaline phosphatase (PLAP)-like enzyme shown by its catalytic and antigenic characteristics, properties which are shared by the Nagao isozyme. More specifically, it is L-leucine sensitive just as is the rare placental D-variant of PLAP and the testicular heat-stable enzyme. Collectively, these are all referred to as PLAP-like enzymes. The enzyme was localized to the surface of the plasma membrane since it was released in an active form by bromelain treatment of cells. The number of molecules per A431 cell was estimated by radioimmunoassay at 7.5 X 10(5), a value significantly higher than that observed for HeLa TCRC-1 cells (5 X 10(4) which express the S-variant of PLAP, also referred to as the Regan isozyme. The quantity of the enzyme was increased significantly (10-fold) by treating the cells with modulating agents including sodium butyrate, prednisolone, and hyperosmolar sodium chloride. The identification of a cell line such as A431 with enhanced expression in the amount of the PLAP-like enzyme and which can be further enhanced by modulating agents will facilitate studies of the differences and the similarities between this protein and other variants of PLAP. The A431 cell line now takes its place with other cell lines which are phenotypically restricted in their expression of alkaline phosphatase. Finally, the A431 cell line is also shown here to be a suitable model system for in vivo tumor studies such as immunolocalization. PMID- 2578099 TI - Impaired in vitro interferon, blastogenic, and natural killer cell responses to viral stimulation in acquired immune deficiency syndrome. AB - The in vitro immune response to herpes simplex virus (HSV), type 1, strain 539, HSV type 2, strain 316D, and cytomegalovirus was studied in 20 patients (14 with acquired immune deficiency syndrome, four with the acquired immune deficiency syndrome-related symptom complex, and two sexually active asymptomatic homosexuals) and 18 heterosexual healthy controls. Peripheral blood mononuclear cells were cultured with 2 X 10(5) plaque-forming units of heat-inactivated viruses, their lymphocyte blastogenic responses were measured after 5 days in culture by [3H]-thymidine incorporation, their interferon production was measured after 24 hr and 5 days, and natural killer (NK) cell activation was measured after 24 hr and 5 days of culture. Blastogenic responses to viruses were significantly low for only HSV, type 1:1.75 X 10(3) cpm in patients' cells compared to 6.36 for controls. Interferon responses to all three viruses were significantly low at both 24 hr and 5 days; e.g., HSV, type 1:139 IU/ml in patients' cells compared to 777 for controls at 24 hr. NK cell responses of patients were lower than those of controls when tested fresh and after 24 hr of incubation: 6.1 versus 11.7% and 9.2 versus 16.8% target cell lysis, respectively. Exposure to viruses boosted NK cell responses of both patients' and controls' cells, but boosting was generally greater among the normal rather than the patients' cells. The abnormalities of response were present in all three patient groups. Addition of interleukin-2 in vitro increased the patient and control blastogenic and NK responses but did not augment the interferon responses. The in vitro responses to both HSV, type 1, and HSV, type 2, correlated significantly with our conventional assays of the percentage and absolute level of T4+-helper lymphocytes in the blood and the blastogenic responses to mitogens, such as phytohemagglutinin, pokeweed mitogen, and concanavalin A. This system should be useful for the study of host defense in acquired immune deficiency syndrome patients and those in high-risk groups, and also for the in vitro evaluation of immunomodulators. PMID- 2578100 TI - Effects of ionizing radiation on cells from Fanconi's anemia patients. AB - The lymphocytes from some Fanconi's anemia patients appeared to be more radiosensitive than normal as measured by the number of X-ray-(or bleomycin-) induced chromosome aberrations seen following G2 treatment. Fibroblasts from the same patients, however, all showed the same degree of colony survival as normals following exposure to gamma-rays [Do, 1.13 +/- 0.072 (S.E.) Gy and 1.14 +/- 0.077 Gy for Fanconi's anemia and normal fibroblasts, respectively]. The lack of increased radiosensitivity in Fanconi's fibroblasts was also observed by the same degree of inhibition of DNA synthesis as seen in normals following gamma irradiation. The results show clearly that there is no increase in radiosensitivity common to all cell types from Fanconi's patients, although an apparent increase in chromosomal radiosensitivity may be seen in the lymphocytes from an occasional patient. PMID- 2578101 TI - Formation of 7-hydroxymethotrexate polyglutamyl derivatives and their cytotoxicity in human chronic myelogenous leukemia cells, in vitro. AB - The rapid synthesis of poly-gamma-glutamyl derivatives of 7-hydroxymethotrexate (7-OH-MTX) and their selective intracellular retention are reported in human chronic myelogenous leukemia cells, K-562. After a 30-min exposure to 5 microM [3H]7-OH-MTX, three different polyglutamyl derivatives were detected by high performance liquid chromatography. When extracellular 7-OH-MTX was removed, the 7 OH-MTX diglutamate level declined slowly in comparison to the monoglutamate, but the higher polyglutamyl derivative levels increased. Within 10 min after exposure of cells to 7-OH-MTX, the level of these polyglutamyl derivatives far exceeds the dihydrofolate reductase binding capacity. Gel filtration or charcoal binding analysis followed by high-performance liquid chromatography analysis of the bound component showed intracellular binding of virtually all 7-OH-MTX tetraglutamate at a level 4-fold higher than that of the dihydrofolate reductase binding capacity. No bound 7-OH-MTX diglutamate or triglutamate could be detected. Treatment of the 7-OH-MTX tetraglutamate: protein complex with 100 microM unlabeled methotrexate (MTX) for 15 min resulted in only a partial dissociation of this complex to an extent compatible with the dihydrofolate reductase level. The residual 7-OH-MTX tetraglutamate remained bound to a site with a molecular weight of approximately 25,000 to 35,000 as assessed by Bio-Gel P-60 analysis and could not be displaced by folic acid, 5-formyltetrahydrofolate, 7-OH-MTX, or the tetraglutamate of MTX. 7-OH-MTX and MTX cytotoxicities were compared by clonogenic assay in agar and by their effects on cell growth. After a 2-hr exposure, the 50% inhibitory concentrations for 7-OH-MTX and MTX in cells growing in agar were 10(-5) and 10(-6) M, respectively. A 10-fold difference in cytotoxicity was also observed in cells growing in suspension. Continuous exposure to glycine: adenosine: thymidine completely protects cells from a sustained exposure to 7-OH-MTX over the entire period of clonal growth. However, even a brief exposure to 7-OH-MTX also requires continuous exposure to glycine: adenosine: thymidine for protection. This suggests that, as observed for MTX, the 7-OH-MTX polyglutamyl derivatives that are retained within the cells have a sustained cytotoxic effect after the monoglutamate is removed. PMID- 2578102 TI - Efficiency in the diagnosis of acute pancreatitis increased by improved electrophoresis of amylase isoenzyme P3 on cellulose acetate. AB - Serum from patients who have suffered acute pancreatitis contains P3, an isoenzyme of pancreatic-derived amylase (EC 3.2.1.1). Heretofore, complete resolution of P3 from the major salivary isoenzyme in serum, S1, has not been possible, thus compromising the diagnostic potential of P3 for pancreatitis. I describe an electrophoretic method for the essentially complete resolution of P3 from S1 by including CaCl2, 1 mmol/L, in the Tris barbiturate electrophoresis buffer (25 mmol/L, pH 8.8). I evaluated the clinical utility of the method for 129 consecutive patients suspected of having pancreatitis, by using receiver operating characteristic curve analysis for results for total amylase, P2, and P3 activity. For a true-positive rate of 90% with a prevalence of pancreatitis of 7.8%, the diagnostic efficiency was increased from 82% (total amylase) to 91% (P2) to 98% (P3). Thus, including P3 activity in the diagnostic criteria will eliminate most false-positive results for pancreatitis based on total amylase activity alone, and should decrease the need for expensive radiologic procedures currently required to confirm the presence of pancreatitis. I conclude that P3 can be of significant value in the differential diagnosis of pancreatitis from other syndromes with hyperamylasemia. PMID- 2578103 TI - Autoantibodies to the basal cells of squamous epithelium react with thymic epithelial cells. AB - Sera from carriers of hepatitis B surface antigen (17 out of 21), which reacted in immunofluorescence with the basal cell layer (BCL) of squamous epithelium, were also shown to react with a thymic stellate epithelial cell (SEC) characterized by long, dendritic-like cytoplasmic processes. Absorption of the autoantibodies against BCL of squamous epithelium (BCL-Ab) with a thymic homogenate abolished the reactivity with BCL and SEC, demonstrating that the same antigenic determinant was recognized in both cells. In the human thymus, SEC were present both in the cortex and in the medulla. In the outer cortex SEC delineated the septal spaces. SEC were also stained by anti-HLA-DR (Ia) but not by antiactin monoclonal antibodies. The morphology and distribution of SEC were similar to those of the previously described thymic epithelial cells containing alpha-1 thymosin (K. Hirokawa, J. E. McClure, and A. L. Goldstein, Thymus 4, 19, 1982). BCL-Ab were also found to react with five human epithelial thymomas. BCL-Ab seemed to be useful for further characterization of the thymic epithelial cells and for the immunodiagnosis of thymoma. PMID- 2578104 TI - IgM class antibodies to intercellular substance in massive cutaneous hyalinosis: occurrence and relation to antigluten and antihyalin antibodies. AB - High levels of circulating IgM class antibodies to intercellular substance were found in massive cutaneous hyalinosis, a systemic kappa light chain disease characterized by hyalin deposits in skin and gut. A strong humoral immune response to the accumulating mannose-rich hyalin glycoprotein and to wheat gluten was also demonstrated. Both gluten and the hyalin protein, when added to serum, abolished the immunofluorescence staining of the intercellular cement, suggesting that there may exist common antigenic sites in the hyalin protein, gluten, and intercellular substance. PMID- 2578105 TI - Inhibition by alpha-fetoprotein fractions of hemagglutination reactions between A and B antigens of human red blood cells and specific antisera. AB - It is shown that fetal alpha-fetoprotein (AF)-rich fractions, isolated by chemical methods, can inhibit the agglutination reaction of human AB red blood cells (RBC) with specific antisera. Hemagglutination was not inhibited by other amniotic fluid or umbilical cord serum proteins in equivalent concentrations or by other pregnancy-associated hormones. The inhibitory effect is related to the amount of antibodies and AF fractions. It seems that AF interferes with the interaction between the antibody and the cell-surface antigens by preventing the binding of the antibodies to the cells. It is suggested that the ability of AF to inhibit hemagglutination reactions in vitro may play a role during pregnancy on the immune reaction between anti-A and anti-B antibodies and the corresponding RBC antigens, as well as on the manifestations or hemolytic disease of the newborn. PMID- 2578106 TI - Differences in lithium effects in depressed and healthy subjects. AB - To evaluate the neurotransmitter actions of lithium without the confounding biochemical abnormalities associated with affective disorders, Li was given to 12 hospitalized healthy young men. After a 600-mg loading dose, subjects were placed on "therapeutic" Li doses averaging 1225 +/- 300 mg for 1 wk, reaching steady state plasma levels of 0.82 +/- 0.17 mEq/l. Cardiovascular function at rest and diastolic blood pressure and pulse on standing were not altered by Li. Average baseline plasma norepinephrine (NE) concentration in the supine position (1.07 +/ 0.50 pmol/ml) did not change after 1 wk of Li dosing (1.16 +/- 0.57 pmol/ml). There was similar variability, without mean change, in plasma NE increments after orthostatic challenge and in plasma 3-methoxy-4-hydroxyphenylglycol concentrations before and during Li dosing. Urine volume was stable throughout the week of drug dosing, during which daily NE excretion was constant. In contrast to earlier data obtained in patients with depression receiving Li, there were no Li-related decrements in average whole-body NE or dopamine turnover. Mean daily urinary excretion rates of serotonin and its major metabolite 5 hydroxyindoleacetic acid did not change throughout the study. Our and other studies suggest that Li has a corrective action in patients with depression and hypothesized neurotransmitter abnormalities, but Li does not affect individuals without affective disorders. PMID- 2578108 TI - Serum amylase in pancreatitis. PMID- 2578107 TI - Effects of verapamil on exocrine pancreatic secretion in man. AB - Calcium ions are thought to mediate hormonal and cholinergic stimulation of exocrine pancreatic secretion. In order to further eludicate the role of calcium ions in stimulus-secretion coupling of the pancreas, the effect of the calcium antagonist verapamil, which inhibits transmembrane calcium influx, was studied on pancreatic secretion in 35 healthy male volunteers. Every subject had two stimulation periods of 2 hr each with a 3-hr period between the two. Pancreatic secretion was stimulated by cholecystokinin in 12 subjects, by secretin in 14 subjects, and by sham feeding in 6 subjects. Three subjects were studied without any secretory stimulus. Verapamil as an intravenous bolus of 150 micrograms/kg followed by an intravenous infusion of 150 micrograms/kg/hr or saline were given during the two 2-hr stimulation periods in a randomized order. The pancreatic secretory responses to stimulation by cholecystokinin, secretin, or sham feeding, as well as the basal pancreatic secretion without a secretory stimulus were left unaffected by verapamil when compared to the saline control. The results, therefore, call into question the hypothesis that transmembrane calcium influx is a major mediator of pancreatic secretion in response to hormonal or cholinergic stimulation in man. PMID- 2578109 TI - Monoclonal antibodies to the human laminin receptor recognize structurally distinct sites. AB - Laminin, a glycoprotein of basement membranes, binds to a specific receptor on the surface of neoplastic and non-neoplastic cells. The laminin receptor purified from human breast carcinoma plasma membranes was used as an antigen to generate two types of monoclonal antibodies (mAbs). Both types of mAbs bind to (a) the purified receptor coated on a solid phase; (b) isolated breast carcinoma plasma membranes; and (c) the surface of cultured MCF-7 human breast carcinoma cells by immunohistology. Using immunoblotting, both types of mAbs recognize a single 67 000 Dalton protein among all the proteins extracted from breast carcinoma plasma membranes. The mAbs differed in their ability to block binding of laminin to the plasma membrane receptor. Antibody LR1 inhibited virtually 100% of the specific binding of laminin to both the isolated human breast carcinoma plasma membranes or the living MCF-7 cells. In contrast, antibody LR2 had no effect on laminin binding under identical conditions. Thus, the two types of mAbs may recognize structurally distinct sites on the laminin receptor. These mAbs should be useful to dissect the biology and the molecular genetics of the laminin receptor. PMID- 2578110 TI - Accumulation of autolysosomes after receptor-mediated introduction of Ep459 asialofetuin conjugate into lysosomes in rat hepatocytes. AB - Administration of Ep459-asialofetuin conjugate (Ep459-AF) and pepstatin asialofetuin conjugate (Ps-AF) to rats effectively inhibited lysosomal BANA hydrolase and cathepsin D in the liver, respectively, at a very low dose. Ep459 AF treatment also led to an accumulation of autolysosomes in rat liver. There was a close correlation between the accumulation of autolysosomes and the inhibition of BANA hydrolase activity. However, as opposed to the inhibition of thiol proteases, the inhibition of cathespin D did not cause accumulation of autolysosomes in the rat liver. These results suggest that autophagy in rat hepatocytes is a common occurrence under normal physiological conditions and that thiol proteases are digestive enzymes essential for the autolysomes. PMID- 2578111 TI - Monoclonal antibodies to mitochondrial coupling factor B. AB - Two monoclonal antibodies (MAb I and IV) have been prepared which showed high and specific reactions towards bovine heart mitochondrial coupling factor B (FB). Both have been identified as sub-type IgG1 of mouse immunoglobulins. MAb I reacts with purified and functionally active FB, alkylated or oxidized forms of FB and even with peptides formed on digestion of FB with trypsin. When used together, MAb I and IV reacted with FB in immunoblots of normal and urea treated samples of mitochondria, submitochondrial particles, ammonia-EDTA extracted particles, and H+-ATPase. Both MAbs inhibited FB-stimulated ATP-dependent reverse electron flow activity when FB was incubated with the antibody either before or after its addition to FB-deficient AE-particles. Reactivity of MAb I towards FB declined upon exposure of FB to guanidine HC1 while reactivity of MAb IV remained unaltered. PMID- 2578112 TI - pH-sensitive liposomes mediate cytoplasmic delivery of encapsulated macromolecules. AB - Negatively charged liposomes are endocytosed by the coated vesicle system and accumulate in acidic intracellular vesicles. Liposomes that become unstable at acidic pH improve cytoplasmic delivery of membrane-impermeant macromolecules such as calcein (CAL) and FITC dextran (18 or 40 kDa). Oleic acid (OA): phosphatidylethanolamine (PE) (3:7 mole ratio) liposomes become permeable to CAL at pH less than 7.0. Control liposomes of phosphatidylserine:PE or OA:phosphatidylcholine are stable at pH 4-8. OA:PE liposomes promote cytoplasmic delivery of encapsulated CAL to CV-1 cells, as evidenced by the emergence of diffuse, cytoplasmic CAL fluorescence. Delivery requires metabolic energy and is partially inhibited by chloroquine or monensin, which raise the pH of intracellular vesicles. PMID- 2578113 TI - Monoclonal antibodies localize the exchangeable GTP-binding site in beta- and not alpha-tubulins. AB - A combination of several methods was used to localize the exchangeable GTP binding site in the alpha/beta-tubulin heterodimer: direct photoaffinity labeling with [alpha-32P]GTP, specific labeling of alpha- and beta-tubulin by tyrosylation and phosphorylation, respectively, and immunoprecipitation with specific monoclonal antibodies. Direct evidence was obtained that GTP binds exclusively to beta- and not alpha-tubulins. PMID- 2578114 TI - Acridine orange male fertility test. PMID- 2578115 TI - Polyploid tissues in the nematode Caenorhabditis elegans. AB - During larval development, the number of somatic nuclei in C. elegans hermaphrodites increases from 558 to 959 (J. E. Sulston and H. R. Horvitz, Dev. Biol. 56, 110-156, 1977; J. E. Sulston et al., Dev. Biol. 100, 64-119, 1983). At the same time, the animals increase about 60-fold in volume. We have measured the DNA contents of several classes of nuclei by quantitating the fluorescence of Hoescht 33258 stained DNA (D. G. Albertson et al., Dev. Biol. 63, 165-178, 1978). Probably all embryonic nuclei, including those of neurons, muscles, hypodermis, and intestine, are diploid at hatching. Neurons, muscles, and nondividing hypodermal nuclei remain diploid throughout larval development. The DNA content of the intestinal nuclei doubles at the end of each larval stage, reaching 32C by the adult stage. New hypodermal cells, generated by division of seam cells in the larval stages, undergo an additional round of DNA replication before fusing with the major syncytium (hyp7, Sulston et al., 1983). Thus the larval hyp7 syncytium comprises a fixed number of diploid embryonic nuclei plus an increasing number of tetraploid postembryonic nuclei. Some of the endoreduplications that occur in the intestinal and hypodermal lineages of C. elegans may correspond to nuclear or cellular divisions in another nematode Panagrellus redivivus (P. W. Sternberg and H. R. Horvitz, Dev. Biol. 93, 181-205, 1982). PMID- 2578116 TI - Embryonic origin of substance P containing neurons in cranial and spinal sensory ganglia of the avian embryo. AB - The ontogeny of the neurons exhibiting substance P-like immunoreactivity (SPLI) was examined in the spinal and cranial sensory ganglia of chick and quail embryos. It was shown that in dorsal root ganglia (DRG) virtually all neuronal somas occupying the mediodorsal (MD) region of the ganglia are SPLI-positive while the larger neurons of the lateroventral (LV) area are SPLI-negative. In the cranial nerve ganglia, both types of neurons coexist in the trigeminal ganglion but with a different distribution: small neurons with SPLI are proximal while large neurons without SPLI occupy the maxillomandibular and ophthalmic lobes. The distal ganglia of nerves VII and IX (i.e., geniculate, petrosal) do not show cell bodies with SPLI in the two species considered. A few of them only (about 12%) are found in the nodose (distal ganglion of nerve X). The proximal ganglia of nerves IX and X (i.e., superior-jugular complex) are composed of small neurons which virtually all exhibit SPLI. Chimaeric cranial sensory ganglia were constructed by grafting the quail hind-brain primordium into chick embryos. Revelation of SPLI was combined with acridine orange staining on the same sections in order to ascertain the placodal (chick host) or neural crest (quail donor) origin of the SP-positive neurons in each type of ganglion. We found that all the neurons showing SPLI are derived from the neural crest in the trigeminal and in the superior and jugular ganglia. In the geniculate, petrosal, and nodose all the neurons are derived from the placodal ectoderm. The small number of SPLI positive cells of the nodose ganglia are not an exception to this rule. Therefore, generally speaking, the sensory neurons of the cranial ganglia that express the SP phenotype are derived from the crest, with the exception of some neurons present in the nodose of both quail and chick embryos and which are of placodal origin. The vast majority of placode-derived neurons do not have amounts of SP that can be detected under the conditions of the present study. PMID- 2578117 TI - Three cell recognition changes accompany the ingression of sea urchin primary mesenchyme cells. AB - At gastrulation the primary mesenchyme cells of sea urchin embryos lose contact with the extracellular hyaline layer and with neighboring blastomeres as they pass through the basal lamina and enter the blastocoel. This delamination process was examined using a cell-binding assay to follow changes in affinities between mesenchyme cells and their three substrates: hyalin, early gastrula cells, and basal lamina. Sixteen-cell-stage micromeres (the precursors of primary mesenchyme cells), and mesenchyme cells obtained from mesenchyme-blastula-stage embryos were used in conjunction with micromeres raised in culture to intermediate ages. The micromeres exhibited an affinity for hyalin, but the affinity was lost at the time of mesenchyme ingression in vivo. Similarly, micromeres had an affinity for monolayers of gastrula cells but the older mesenchyme cells lost much of their cell-to-cell affinity. Presumptive ectoderm and endoderm cells tested against the gastrula monolayers showed no decrease in binding over the same time interval. When micromeres and primary mesenchyme cells were tested against basal lamina preparations, there was an increase in affinity that was associated with developmental time. Presumptive ectoderm and endoderm cells showed no change in affinity over the same interval. Binding measurements using isolated basal laminar components identified fibronectin as one molecule for which the wandering primary mesenchyme cells acquired a specific affinity. The data indicate that as the presumptive mesenchyme cells leave the vegetal plate of the embryo they lose affinities for hyalin and for neighboring cells, and gain an affinity for fibronectin associated with the basal lamina and extracellular matrix that lines the blastocoel. PMID- 2578118 TI - Role of histamine in the cell turnover changes associated with experimental gastric ulceration in the mastomys. AB - Using an animal model of gastric ulceration, in vivo and in vitro methods were developed to assess the importance of histamine in the cell turnover abnormalities previously found to occur in the preulcerous phase of gastric ulceration induced by mucosal anaphylaxis, and by using specific H1- and H2 receptor agonists and antagonists to define which receptors were involved. In ovalbumin-immunized animals, intramucosal ovalbumin injection led to a highly significant increase in cell turnover as measured by [3H]thymidine uptake (p less than 0.001). This increase was not affected by treatment with the H2 antagonist cimetidine, but was significantly reduced by the H1 antagonists promethazine and clemastine (p less than 0.01). A cell culture method was then used to examine the effects of added histamine and its antagonists. Histamine at a concentration of 10(-7) M was found to have a significant stimulatory effect on cell proliferation (p less than 0.001), and this effect was blocked by promethazine and clemastine but not by cimetidine. In contrast, histamine at a concentration of 10(-2) M had an inhibitory effect on cell proliferation which was accentuated by cimetidine and partially reversed by promethazine and clemastine. The H1 agonist betahistine was found to have stimulatory effects similar to those of histamine in low concentration (10(-7) M and 10(-6) M), but the H2 agonist 4-methyl histamine did not affect thymidine uptake at these concentrations. Both H1 and H2 agonists had a similar inhibitory effect at a concentration of 10(-2) M. It is concluded that histamine probably plays an important part in the changes in cell kinetics associated with gastric ulceration induced by this method, and that the trophic effects of histamine are mediated by H1-receptors. H2-receptors appear to have only a limited role in the control of cell proliferation. PMID- 2578119 TI - Nufenoxole, a new antidiarrhoeal agent, inhibits fluid secretion in the human jejunum. AB - Nufenoxole is an orally active antidiarrhoeal agent which binds to opioid receptors in the brain and myenteric plexus of the intestine. A perfusion technique has been used to investigate the effect of nufenoxole (1 mg/kg intrajejunally) on water and solute transport stimulated by the secretagogue, dioctyl sodium sulphosuccinate, in the human jejunum in vivo. Nufenoxole reversed the direction of jejunal transport of salt and water from net secretion to net absorption. These changes in water and electrolyte transport were inhibited by intravenous naloxone, the opioid antagonist. Nufenoxole possesses potent antisecretory properties, which are mediated via opioid receptors and may contribute to its antidiarrhoeal action in man. PMID- 2578120 TI - Effect of phenethyl alcohol on Staphylococcus aureus alpha-lysin production. AB - Phenethyl alcohol, at the maximum concentration which did not inhibit growth (0.3% [vol/vol]), inhibited the production of alpha-lysin and exoproteases but not that of delta-lysin in Staphylococcus aureus Wood 46. The inhibition of alpha lysin was reversible, and transient accumulation of cell-associated alpha-lysin occurred in the presence of PEA. A precursor of alpha-lysin ca. 3,000 daltons larger than extracellular alpha-lysin was immunologically detected in the sodium dodecyl sulfate extracts of membranes and whole cells of phenethyl alcohol treated S. aureus cultures. Also, a degraded form of alpha-lysin was detected in membranes prepared from cells lysed by lysostaphin but not in membranes from cells lysed with an X-press. PMID- 2578121 TI - A minor high-molecular-weight outer membrane protein of Haemophilus influenzae type b is a protective antigen. AB - Cell surface-exposed antigenic determinants of several high-molecular-weight outer membrane proteins of Haemophilus influenzae type b (Hib) have been shown to be consistently immunogenic in human infants convalescing from Hib meningitis. A monoclonal antibody (mab), 6G12, directed against one of these cell surface exposed outer membrane proteins that has an apparent molecular weight of 98,000 (98K) was identified by radioimmunoprecipitation analysis. Of 120 clinical isolates of Hib, 83 were found to possess antigenic determinants which reacted with mab 6G12 in a colony blot-radioimmunoassay procedure, indicating that the antigenic determinant recognized by mab 6G12 is present in the majority of Hib strains. A different radioimmunoassay, which uses whole Hib cells as antigen, confirmed that strains reactive with mab 6G12 in the colony blot-radioimmunoassay procedure possessed a cell surface-exposed and antibody-accessible antigenic determinant recognized by this mab. Hib strains which did not react with mab 6G12 were found to lack a 98K protein. Passive immunization with mab 6G12 reduced the level of bacteremia that developed in infant rats challenged with the homologous Hib strain against which this mab was raised. In contrast, no protection was observed when the challenge strain was one which lacks the antigenic determinant recognized by mab 6G12. Radioimmunoprecipitation analysis of sera from human infants convalescing from Hib meningitis detected an antibody response directed against the 98K protein. The protection against experimental Hib disease provided by antibody to the 98K protein, the immunogenicity of this protein in human infants, and its presence in a majority of Hib strains indicate that the 98K outer membrane protein may have potential for vaccine development. PMID- 2578122 TI - Factors affecting binding of galacto ligands to Actinomyces viscosus lectin. AB - The specificity requirements for the binding of Actinomyces viscosus T14V were examined by testing simple sugars, oligopeptides, and glycoproteins as inhibitors of the aggregation of glycoprotein-coated latex beads and washed A. viscosus cells. Lactose was the most inhibitory simple sugar; D-fucose and D-galactose were equally inhibitory, methyl-alpha-D-fucoside was slightly less inhibitory, and L-fucose and raffinose were not inhibitory. The concentration of galactose residues required for 50% inhibition of aggregation was 15 times higher in the form of lactose than in the form of asialoglycoprotein, suggesting an enhancement of lectin binding when galactose residues are clustered. However, when the inhibitory power of bi-, tri-, and tetraantennary asialooligopeptides of alpha 1 acid glycoprotein was compared with that of equivalent concentrations of galactose in the form of lactose, the biantennary form was slightly less effective than lactose, the triantennary form was approximately as effective as lactose, and the tetraantennary form was slightly more effective than lactose. Steric interference may prevent this type of clustering from enhancing lectin binding. The O-linked asialooligopeptides of asialofetuin were 10 times more inhibitory than an equivalent concentration of galactose in the form of N-linked asialooligopeptides. Thus, galactose beta-1----3 linked to N-acetylgalactosamine exhibits greater specificity for the A. viscosus lectin than does galactose beta 1----4 linked to N-acetylglucosamine. These results, taken together with previously reported data, are consistent with a lectin of low affinity, binding enhanced by multivalency, and specificity for beta-linked galactose. PMID- 2578123 TI - Effects of phospholipase A2 inhibitors on ruthenium red-induced Ca2+ release from mitochondria. AB - The pharmacologic agents verapamil, nifedipine, diltiazem, prenylamine, N oleoylethanolamine, R 24571, trifluoperazine, dibucaine, and quinacrine are examined as potential inhibitors of rat liver mitochondrial phospholipase A2 acting on endogenous phospholipid. Their potency as inhibitors of the enzyme is compared to their activities as inhibitors of phospholipase A2-dependent swelling and ruthenium red-induced Ca2+ release in intact mitochondria. For verapamil, diltiazem, trifluoperazine, dibucaine, and quinacrine, there is complete agreement between the relative potencies as inhibitors of phospholipase A2 and the two other processes. Nifedipine and prenylamine, which are weak inhibitors of phospholipase A2, produce a permeable inner membrane, provided that the mitochondrial have accumulated Ca2+. R 24571, which strongly inhibits the enzyme, disrupts mitochondria by a Ca2+-independent mechanism. N-Oleoylethanolamine, which is an effective inhibitor of swelling, does not inhibit phospholipase A2 or ruthenium red-induced Ca2+ release. The results support a proposed scheme wherein ruthenium red-induced Ca2+ release is viewed as reverse activity of the Ca2+ uptake uniporter occurring subsequent to decline in the proton motive force. The latter effect is proposed to arise from a specific phospholipase A2-dependent increase in inner-membrane H+ conductance of mitochondrial subpopulations. It is further shown that mitochondrial membranes display cyclic oscillations in free fatty acid content which are not dependent on the presence of Ca2+ or on the capacity to generate acylcoenzyme A. PMID- 2578124 TI - Correlation of chloroplast and bacterial ribosomal proteins by cross-reactions of antibodies specific to purified Escherichia coli ribosomal proteins. AB - Immunological homology between chloroplast ribosomal proteins (r-proteins) from a higher plant (Spinacia) and bacterial r-proteins was examined using antibodies prepared against 35 purified Escherichia coli r-proteins. Cross-reactions were determined on cellulose acetate gels and on nitrocellulose paper, after electrophoretic transfer of r-proteins from one- and two dimensional polyacrylamide gels, using peroxidase and fluorescein-conjugated second antibodies for detection (immunoblotting). The specificity of positive cross reactions was confirmed by absorption experiments using purified E. coli r proteins. Antisera against five proteins of the small subunit and six proteins of the large subunit of E. coli ribosome (i.e. anti-S7, -S9, -S11, -S12, and -S19; anti-L1, -L2, -L3, -L6, -L13, and -L17) gave cross-reactions. As an inference from this work, and a recent study on the synthesis of certain chloroplast r proteins in isolated chloroplasts (Eneas-Filho, J., Hartley, M. R., and Mache, R. (1981) Mol. Gen. Genet. 184, 484-488), we suggest that chloroplast r-proteins S7 and L2 are encoded in the organelle DNA. PMID- 2578125 TI - The kinetics of activation of normal and gamma-carboxyglutamic acid-deficient prothrombins. AB - The kinetics of activation of normal and gamma-carboxyglutamic acid (Gla) deficient prothrombins isolated from cattle maintained for extended periods on the vitamin K antagonist dicoumarol were studied. The catalyst was prothrombinase, comprising isolated Factor Xa, Factor Va, phospholipid vesicles, and calcium ion. The Km and kcat values for prothrombins with 0, 1, 2, 5, 7, and 10 Gla residues were determined both by initial rate analysis and by integrated Michaelis-Menten-Henri analysis. Each of the Gla-deficient prothrombins exhibited kcat values similar to that of normal 10-Gla prothrombin but Km values that were 8- to 20-fold greater than that of the normal molecule. The increased Km coincided with a loss of Ca2+- and phospholipid-binding properties of the Gla deficient prothrombins. The magnitude of the defect in both the kinetics of activation and Ca2+ and phospholipid binding is not progressive with the loss of Gla residues but rather appears abruptly with the loss of as few as 3 of the 10 Gla residues present in the normal substrate. The theoretical relationship between Km(app) and the dissociation constant (Kd) of the prothrombin phospholipid interactions was derived. According to the result, the increase in apparent Km observed with the Gla-deficient prothrombins corresponds to at least a 100- to 1000-fold decrease in affinity for phospholipid compared to the affinity of normal prothrombin. In addition, the products of the activation of 10 Gla prothrombin were found to inhibit the activation of the Gla-deficient prothrombins. PMID- 2578126 TI - Purification of an active EGF receptor kinase with monoclonal antireceptor antibodies. AB - A method is described for a rapid two-step purification of the membrane receptor for epidermal growth factor (EGF) from cultured human A-431 cells. After solubilization of the cells with Triton X-100, the receptor is immobilized on an immunoaffinity column containing a monoclonal antibody directed against the receptor. In the second step of purification, the receptor, eluted from the antibody column, is adsorbed and specifically eluted from a lectin-agarose column. The molecular species obtained is mainly the 170,000-dalton EGF receptor polypeptide. The activity of the pure receptor depends on the conditions used for the desorption from the immunoaffinity beads. High-yield elution is obtained with acidic buffer and the receptor so purified specifically binds EGF, but is devoid of the kinase activity. When the elution is done with alkaline buffers or with buffer containing urea, a fully active receptor kinase is purified (yield of 10%). The pure receptor binds 125I-EGF with a Kd of 4 X 10(-8) M and retains EGF sensitive protein kinase activity which phosphorylates tyrosine residues on the receptor itself. An additional protocol is described for large-scale purification (yield of 55%) of EGF receptor for the analysis of its primary structure. In this procedure, the EGF receptor is first purified by immunoaffinity chromatography which is followed by preparative gel electrophoresis of the 32P internally labeled receptor to remove minor protein contaminants. PMID- 2578127 TI - A reinvestigation of the amino acid sequences of bovine, rabbit, monkey, and human myelin basic proteins. AB - In order to determine whether bovine, rabbit, and monkey myelin basic proteins (BPs) have the sequence Gly-His or His-Gly at positions corresponding to bovine sequence 76-77, we isolated the tryptic peptides encompassing the sequence in question in these proteins and cleaved them into dipeptides with dipeptidyl aminopeptidase I (EC 3.4.14.1). Analysis by gas chromatography/mass spectrometry of the dipeptides released showed that in no case did His follow Gly or Gly precede His. The identification of peptides Ala-Gln and His-Gly (bovine BP) and Ser-His and Gly-Arg (rabbit and monkey BPs) established the His-Gly sequence. A similar sequence analysis of tryptic peptide (80-91) of human BP confirmed the sequence Thr-Gln-Asp-Glu-Asn-Pro (80-85). PMID- 2578128 TI - Characterization of human beta-interferon-binding sites on human cells. AB - Radioiodinated recombinant human beta-interferon (rHuIFN beta Ser), with almost full (greater than 90%) biological activity, was used to study the binding of human beta-interferon to Daudi cells. Specific binding was not observed with less biologically active (less than or equal to 10%) radioiodinated interferon. The bound radioiodinated interferon was shown to compete with human beta-interferon (HuIFN beta), rHuIFN beta Ser, human alpha-interferon (HuIFN alpha) and with human gamma-interferon (HuIFN gamma). Scatchard plot analyses suggest the presence of about 10,000 binding sites for HuIFN beta/Daudi cell. About 6,600 of these sites can be blocked by HuIFN alpha and 3,700 sites can be blocked by HuIFN gamma. The apparent Kd for HuIFN beta is 2.7 nM. The apparent Kd values for HuIFN alpha and HuIFN gamma are 3.7 and 1.1 nM, respectively. It was possible to demonstrate the cross-linking of HuIFN beta to two macromolecular components of Mr = 128,000 and 103,000. We propose the existence of at least two binding sites for HuIFN beta in Daudi cells, one site recognizing both HuIFN beta and HuIFN gamma, the other site recognizing both HuIFN beta and HuIFN alpha. Each site is capable of recognizing only HuIFN gamma or HuIFN alpha. PMID- 2578130 TI - Cyclic AMP-independent processes mediate Kirsten sarcoma virus-induced changes in collagen production and other properties of cultured cells. AB - Previous studies suggested that the decreased collagen production observed in Kirsten sarcoma virus (Ki-MSV)-transformed BALB 3T3 cells could be reversed by treating cells with Bt2cAMP. We examined the relationship between intracellular cAMP, collagen production, and other properties in NRK and BALB 3T3 cells transformed by Ki-MSV. Two 3T3 transformants (Ki-3T3-234 and Ki-3T3Cl1) had lower cAMP levels than nontransformed cells. The level in a temperature-sensitive transformant, tsKi-3T3-714, was similar to the level in its parent, 3T3-714, and when it was shifted to a temperature nonpermissive for transformation (40 degrees C), intracellular cAMP did not increase although the growth and morphological properties were normal. The relative rate of collagen production also increased to the normal level. These results indicate that transformation-induced changes were regulated independently of cAMP. Further observations supported this conclusion. Intracellular cAMP in a flat revertant of Ki-3T3Cl1 was lower, rather than higher, than in the transformant, although the relative rate of collagen production was higher. Treatment of Ki-3T3-234 and tsKi-3T3-714 with cholera toxin plus isobutylmethylxanthine increased intracellular cAMP concentrations to 2-20 times the level in untreated cells, levels much higher than in nontransformed 3T3. In spite of this, collagen production was not increased by these agents in tsKi-3T3-714 and it was only partially restored in Ki-3T3-234 relative to the level in the nontransformed cells. In contrast, these agents inhibited growth on a substratum or in soft agar and produced a flattened morphology in both lines. Similarly, collagen production in transformed NRK cells (K-NRK) was only 3% of normal but treatment with Bt2cAMP or cholera toxin plus isobutylmethylxanthine increased production to only one-third the normal level while increasing cAMP to four times the normal level. We conclude that in Ki-MSV transformed BALB 3T3 cells, changes in cAMP may be secondary effects and not related to maintenance of the transformed phenotype. The high levels of cAMP induced by exogenous agents may act on similar targets as those affected by transformation, but reversal of the transformed phenotype by these agents probably occurs by a different mechanism than that originally used to impose the changes. PMID- 2578131 TI - Urokinase-type plasminogen activator and its inhibitor secreted by cultured human monocyte-macrophages. AB - Human blood monocytes in culture differentiate to macrophagelike cells within 1 week. Coinciding with this morphological transition the cells started releasing increasing amounts of the serine proteinase plasminogen activator (PA; Mr 56,000) of the urokinase (u-PA) type and the proteinase inhibitor alpha-2-macroglobulin (alpha 2M). Unlike the cell-associated PA activity, which was also readily detected in fresh monocytes, the activity secreted into the serum-free culture medium could be measured only after treatment of the samples with sodium dodecyl sulphate. Heat or acid treatment of the medium was not sufficient to reveal the PA activity, suggesting that, apart from alpha 2M, another PA-inhibiting substance was present in the culture medium. The inhibitor (Mr 65,000) was found to be synthesized by macrophages and specifically inhibited u-PA activity but not tissue-type PA (t-PA) or plasmin activity. Dexamethasone decreased the secretion of PA by differentiated macrophages without affecting the production of alpha 2M or the PA inhibitor. Dexamethasone also inhibited the morphological differentiation of the cells when added to the monocyte-phase cells. PMID- 2578129 TI - The organizational fate of intermediate filament networks in two epithelial cell types during mitosis. AB - Intermediate filaments (IF) appear to be attached to the nuclear envelope in various mammalian cell types. The nucleus of mouse keratinocytes is enveloped by a cagelike network of keratin-containing bundles of IF (IFB). This network appears to be continuous with the cytoplasmic IFB system that extends to the cell surface. Electron microscopy reveals that the IFB appear to terminate at the level of the nuclear envelope, frequently in association with nuclear pore complexes (Jones, J. C .R., A. E. Goldman, P. Steinert, S. Yuspa, and R. D. Goldman, 1982, Cell Motility, 2:197-213). Based on these observations of nuclear IF associations, it is of interest to determine the fate and organizational states of IF during mitosis, a period in the cell cycle when the nuclear envelope disassembles. Immunofluorescence microscopy using a monoclonal keratin antibody and electron microscopy of thin and thick sections of mitotic mouse keratinocytes revealed that the IFB system remained intact as the cells entered mitosis and surrounded the developing mitotic spindle. IFB were close to chromosomes and often associated with chromosome arms. In contrast, in HeLa, a human epithelial cell, keratin-containing IFB appear to dissemble as cells enter mitosis (Franke, W. W., E. Schmid, C. Grund, and B. Geiger, 1982, Cell, 30:103-113). The keratin IFB in mitotic HeLa cells appeared to form amorphous nonfilamentous bodies as determined by electron microscopy. However, in HeLa, another IF system composed primarily of a 55,000-mol-wt protein (frequently termed vimentin) appears to remain morphologically intact throughout mitosis in close association with the mitotic apparatus (Celis, J.E., P.M. Larsen, S.J. Fey, and A. Celis, 1983, J. Cell Biol., 97:1429-34). We propose that the mitotic apparatus in both mouse epidermal cells and in HeLa cells is supported and centered within the cell by IFB networks. PMID- 2578133 TI - Decreased urinary 5 alpha-androstane-3 alpha,17 beta-diol glucuronide excretion in patients with benign prostatic hyperplasia. AB - Urinary testosterone and 3 alpha-androstanediol (3 alpha diol G) glucuronides together with plasma testosterone, 5 alpha-dihydrotestosterone (DHT), and delta 4 androstenedione (delta 4) were measured in 43 normal young men (18-36 yr old), 23 elderly men without clinically evident prostatic pathology (54-89 yr old), 68 elderly men with benign prostatic hyperplasia (BPH group; 54-91 yr old), and 26 elderly men with well differentiated cancer of the prostate (K group; 63-97 yr old). Plasma testosterone decreased slightly with age in all 3 elderly groups (from 591 to 438, 479, and 444 ng/100 ml, respectively). Plasma DHT, on the contrary, was significantly (P less than 0.01) higher in the BPH group than in the other three groups (68 vs. 30, 37, and 32 ng/100 ml, respectively). Plasma delta 4 was significantly lower (P less than 0.01) in the elderly K group than in all other groups (59 vs. 109, 83, and 78 ng/100 ml, respectively). Urinary testosterone glucuronide decreased with age in all 3 elderly groups (from 109 to 55, 38, and 44 micrograms/24 h, respectively) as a result of decreased androgen production rates with age. All 3 elderly groups also had decreased urinary 3 alpha diol G, from 194 to 123, 55, and 118 micrograms/24 h, respectively. The group of elderly patients with BPH had the lowest mean urinary 3 alpha diol G excretion together with the highest mean plasma DHT. This low urinary 3 alpha diol G excretion, which reflects a decrease in both androgen production and DHT metabolism, suggests a decrease in 3 alpha-hydroxysteroid dehydrogenase activity, which, in turn, could explain the increased DHT availability and tissue retention in most target organs. Moreover, the extent of these modifications in androgen metabolism specific to the BPH condition raises the question of an overall alteration of androgen metabolism in patients with BPH which could be the cause of the disease. PMID- 2578132 TI - Modulation of beta-adrenergic response in rat brain astrocytes by serum and hormones. AB - Purified astrocyte cultures from neonatal rat cerebrum respond to isoproterenol, a beta-adrenergic agonist, with a transient rise in cAMP production. This astroglial property was regulated by serum, a chemically defined medium (serum free medium plus hydrocortisone, putrescine, prostaglandin F2 alpha, insulin, and fibroblast growth factor) and epidermal growth factor. Compared to astrocytes grown in serum-supplemented medium, astrocytes grown in the chemically defined medium were nonresponsive to isoproterenol stimulation, and this difference did not appear to be due to selection of a subpopulation of cells by either medium. The data suggest that a decreased beta-adrenergic receptor number and an increased degradation of cAMP may account for the reduced response to beta adrenergic stimulation. The nonresponsive state of astrocytes in the defined medium was reversible when the medium was replaced with serum-supplemented medium. An active substance(s) in serum was responsible for restoring the responsiveness of astrocytes. Each of the five components of the defined medium had little effect by itself; however, together they acted synergistically to desensitize astrocytes to beta-adrenergic stimulation. On the other hand, epidermal growth factor, a potent mitogen for astrocytes, was very competent by itself in reducing the cAMP response of astrocytes to beta-adrenergic stimulation. Thus purified astrocytes grown in the chemically defined medium appear to be a good model for the study of hormonal interactions and of serum factors which may modulate the beta-adrenergic response. PMID- 2578134 TI - Pulsatile secretion of immunoreactive alpha-subunit in man. AB - We compared the secretion of uncombined alpha-subunit with LH secretion, as measured by RIA in six normal men, an agonadal adult man, and an adult woman with testicular ferminization. Blood samples were drawn every 10 min for 12 h to evaluate pulsatile LH and free alpha secretion. Spontaneous alpha pulses occurred every 120 +/- 60 min (mean +/- SD; range, 40-260) in eugonadal men. The mean alpha pulse amplitude was 0.49 +/- 0.11 ng/ml, representing an increase of 60 +/- 18% above the preceding nadir value. alpha pulses were generally associated with LH pulses, and the amplitudes of concordant alpha and LH pulses were highly positively correlated (r = 0.58; P less than 0.01). The absolute amplitude of concordant alpha peaks was 1.5 +/- 0.7% that of corresponding LH peaks. Additional alpha pulses were noted in each subject for which simultaneous LH fluctuations failed to meet the criteria for pulses. Studies in the agonadal man and in the patient with testicular feminization revealed that the frequency of both spontaneous alpha and LH pulses was increased to approximately twice that in normal men. Gel filtration analysis indicated that all alpha radioimmunoactivity in normal male sera coeluted with [125I]alpha. By contrast, in hypogonadal sera, only 50-60% of alpha immunoreactivity coeluted with [125I]alpha, the remaining activity appeared in the region of LH and FSH and resulted from RIA cross reactivity. We conclude that uncombined alpha-subunit, as well as LH is normally released into the peripheral blood in discrete pulses. In the absence of exposure to androgen, the frequency of these pulses increases, presumably as a consequence of the accelerated release of LRH. However, alpha RIAs overestimate the concentration of uncombined alpha in hypogonadal sera. We propose that the coanalysis of LH and alpha secretory episodes may prove useful in resolving some of the complexities associated with gonadotropin secretory patterns. PMID- 2578135 TI - Experimental allergic encephalomyelitis in guinea pigs. Influence of thymosin fraction V on the disease. AB - Experimental allergic encephalomyelitis (EAE) was induced in strain 13 guinea pigs by sensitization with 10 micrograms of myelin basic protein (BP) in complete Freund's adjuvant (CFA). These animals were treated with saline or with thymosin factor V in 3 different doses in 3 separate experiments. Thymosin had no suppressive effect on the incidence and severity of EAE. PMID- 2578136 TI - Characterization of an antiserum against an axolemma-enriched fraction. AB - An antiserum was raised to rat central nervous system (CNS) axolemma-enriched fractions (AEF), which showed no cross-reactivity with myelin proteins or liver microsomes yet gave an endpoint titer of 1:51 200 to CNS AEF by the enzyme-linked immunosorbent assay (ELISA). Immunochemical staining of electroblotted proteins from rat CNS and peripheral nervous system (PNS) AEFs separated by gel electrophoresis identified a major reactive band at 38.5 kD. CNS AEF also showed major immunoreactivity at 91 kD (+/- 3 kD) and a broad band from 110 kD to 130 kD. By immunoperoxidase staining the antiserum specifically recognized the axolemma of peripheral nerve and synaptic terminals in the CNS. The significance of the specificity is discussed with respect to anti-synaptosome antisera. PMID- 2578137 TI - Acute canine idiopathic polyneuropathy (ACIP) serum demyelinates peripheral nerve in vivo. AB - We examined the in vivo demyelinating activity of serum from dogs with acute canine idiopathic polyneuropathy (ACIP), a Guillain-Barre syndrome (GBS)-like illness. Sera from 6 ACIP cases demyelinated rat sciatic nerves more intensely than 11 control sera. Serum activity increased after guinea pig serum (gps) was added, although gps alone had little effect. ACIP sera did not bind more to whole nerve cross sections or Schwann cells in vitro than control sera, and did not contain elevated antigalactocerebroside titers. We do not as yet know the pathogenic importance of the demyelinating factor in ACIP and control dog serum, or understand its relationship to the demyelinating constituent in serum from humans with GBS. PMID- 2578138 TI - Molecular defect in the sickle erythrocyte skeleton. Abnormal spectrin binding to sickle inside-our vesicles. AB - Although functional abnormalities of the sickle erythrocyte membrane skeleton have been described, there is little quantitative data on the function of the proteins that compose the skeleton. We have examined the association of spectrin, the major skeletal protein, with ankyrin, its high-affinity membrane binding site, and found sickle erythrocytes to have markedly reduced binding. Binding is assayed by incubation of purified 125I-spectrin with spectrin-depleted inside-out vesicles (IOVs) and measurement of the label bound to IOVs. Sickle IOVs bind approximately 50% less ankyrin than do controls IOVs (P less than 0.001). Control experiments show that this reduced binding is not a function of faulty composition or orientation of sickle IOVs, or of reticulocytosis per se. Our least symptomatic patient has the highest binding capacity, suggesting that this abnormality may be related to clinical severity. This trend is supported by experiments showing that asymptomatic subjects with sickle trait, sickle cell anemia and high fetal hemoglobin, and sickle beta +-thalassemia have normal binding, whereas a symptomatic patient with sickle beta zero-thalassemia has abnormal binding. In contrast to what we see with ankyrin in situ on the IOV, when isolated and studied in solution, sickle ankyrin binds normally to spectrin. This discrepancy may be related to preferential purification of the normal ankyrin species or to an abnormal topography of the membrane near the spectrin attachment site. We hypothesize that sickle hemoglobin or perhaps the metabolic consequences of sickling damage the protein skeleton. This damage may alter the surface of the erythrocyte and result in abnormal cell-cell interactions which may be related to clinical severity. PMID- 2578139 TI - Binding of a monoclonal anti-DNA autoantibody to identical protein(s) present at the surface of several human cell types involved in lupus pathogenesis. AB - A monoclonal anti-DNA antibody PME77, spontaneously produced in autoimmune B/W mice, has been found to recognize identical protein(s) present at the surface of several human cell types involved in the pathogenesis of systemic lupus erythematosus: glomeruli, platelets, erythrocytes, T and B cells, and neuronal tissue. Data indicate that protein(s) could represent a major stimulus or the target of anti-DNA autoimmunity and could account for tissue lesions observed in this disease. PMID- 2578140 TI - Quantitative immunocytochemistry of hypothalamic and pituitary hormones: validation of an automated, computerized image analysis system. AB - A limiting factor in the use of immunocytochemistry in experimental endocrine studies has been the lack of a suitable procedure for quantification of immunoreactive hormones. The objective of the present study was the development of an automated, computerized image analysis system adapted to the quantitative analysis of light microscopic immunocytochemical reaction product. Reaction conditions that result in optimum, standardized, and quantitatively linear development of reaction deposit are described for H2O2 and diaminobenzidine concentrations, antiserum dilutions, and substrate incubation times. In addition, evaluation techniques, including the use of a standard control section to monitor variance and incorporate it into the statistical analysis of the results are documented. For each of the reaction variables, the immunostaining was linear over the range of specific staining. When the optimum conditions were exceeded, marked over-estimations of hormone levels occurred due to the detection of nonspecific background features reaching the detection threshold. Application of this quantitative immunocytochemical (QICC) method to the analysis of variations in hypothalamic and pituitary hormone levels was validated by comparing values obtained with QICC to those with radioimmunoassay (RIA). The relative changes in both hypothalamic gonadotropin-releasing hormone and pituitary luteinizing hormone induced by manipulation of gonadal steroid levels, as measured by RIA and QICC, were highly correlated. Two-way analysis of variance revealed that the two techniques were not significantly different in their detection of changes in either hormone. Thus, under optimally defined conditions, quantitative immunocytochemistry using computerized image analysis has been validated for the accurate measurement of pituitary and brain hormones in precise regions. PMID- 2578141 TI - Methodologic and genetic influence on immunohistochemical demonstration and semiquantitation of blood group antigen A in human ureter urothelium. AB - In order to improve the accuracy and prognostic value of ABH blood group antigen loss in urothelial tumors, the effect of Lewis blood type and methodologic factors on detectability and distribution of blood group antigen A in human formalin-fixed, paraplast-embedded urothelium and endothelium was investigated by means of the Tween 20-modified indirect immunoperoxidase staining technique. Urothelium of Lea-b+ and Lea-b- individuals expressed significant higher amounts of blood group antigen A compared to urothelium of Lea+b- individuals. The expression on endothelial cells was related to vessel type and size, but not related to Lewis types. Compared to human anti-A, monoclonal anti-A demonstrated blood group antigen A with higher sensitivity and, due to reduced background staining, higher specificity. Consequently monoclonal anti-A detected blood group antigen A in the urothelium of Lea+b- individuals where human anti-A failed to stain, and different staining patterns became apparent. Both a two- to fourfold variation in the proportion between tissue section area and volume, and the volume of anti-A applied induced minor changes in sensitivity and specificity. The monoclonal anti-A method and knowledge about erythrocyte Lewis types might prove valuable in evaluating changes in blood group antigen-A expression in urothelial tumors. PMID- 2578142 TI - Conjugated avidin binds to mast cell granules. AB - The glycoprotein, avidin, conjugated either to the enzyme horseradish peroxidase, or to the fluorochrome dyes, fluorescein or rhodamine, identifies the granules of mast cells in both tissues and cell suspensions. In the absence of prior fixation, mast cells were not identified with conjugated avidin; however, granules released from these cells were stained with this labeled glycoprotein. The specificity of avidin for mast cells was confirmed by the absence of conjugated avidin-positive cells in the skin of mice (S1/S1d) deficient in mature dermal mast cells. Electron microscopic studies confirmed that avidin binds specifically to individual mast cell granules rather than to other cellular structures. Rodent and human mast cells were readily stained with avidin conjugated to horseradish peroxidase or to either of the fluorochrome dyes. The conjugated avidin staining technique is a reliable and simple method for identifying rodent and human mast cells, one that is useful as both an investigative and a clinical tool. PMID- 2578143 TI - Histochemical localization of galactose-containing glycoconjugate at peripheral nodes of Ranvier in the rat. AB - Lectin-horseradish peroxidase conjugates were used to study glycoconjugates in paraffin sections of dorsal roots of the rat spinal cord. Griffonia simplicifolia B4 isolectin (GSA I-B4) and peanut agglutinin (PNA) stained strongly the nodes of Ranvier, localizing, respectively, terminal alpha- and beta-D-galactose. Sialidase digestion did not increase staining with PNA at the node of Ranvier, suggesting the presence of a neutral glycoconjugate. Staining of the nodal but not the internodal axolemma was observed with PNA. The outer surface of the myelin sheath in axons of the dorsal root stained strongly with GSA I-B4 but only weakly with PNA, demonstrating an abundance of terminal alpha-galactose. PNA staining was enhanced in this site by sialidase digestion, showing terminal sialic acid-beta-galactose dimers. The presence of sialic acid here was further evidenced by labeling of these membranes with the lectin derived from the slug, Limax flavus (LFA). Affinity for a high iron diamine-Alcian blue (pH 2.5) sequence demonstrated, in addition, the presence of sulfate esters in glycoconjugates on the outer myelin membrane. GSA I-B4 imparted strong reactivity to nonmyelinated fibers in the dorsal root and the spinal nerve. The present findings appear to reflect several localizations of biochemically described nervous system glycoproteins containing O-glycosidically linked side chains terminated by alpha- and beta-D-galactose. PMID- 2578144 TI - An improved method of preparing nuclei for absorption cytophotometry. AB - An improved method of isolating nuclei from tissue for Feulgen-DNA measurements has been developed. The optimal nuclear isolation medium (NIM) was found to be a solution of 2% polyethylene glycol (PEG) and 0.6% NP40 in phosphate-buffered saline. The disaggregation procedure consists of gentle mechanical disruption of the tissues, followed by a 10 min incubation in the NIM at room temperature. The mixture is then syringed four times through a 27-gauge needle, and the nuclei are placed onto slides with a cytocentrifuge. Nuclei prepared in NIM without PEG had obvious DNA leakage and tended to form clumps. Addition of PEG to the NIM led to separation of nuclei without any DNA leakage, thus greatly increasing the accuracy of the DNA cytophotometry results. G0/G1 nuclei at the appropriate ploidy levels were found for non-transformed and transformed tissues prepared with this technique. In addition, S-phase liver nuclei prepared in this manner showed the expected incorporation of (3H) thymidine after a 1/2 hr pulse in vivo. PMID- 2578145 TI - A double fluorescence method for determining doxorubicin distribution and vascular supply in the mouse kidney. AB - Freeze-sectioning followed by freeze-drying completely preserves the topographic distribution of soluble substances, with the additional advantage of permitting permanent mounting. This rapid and effective technique was applied to study the distribution of fluorescence of the cytotoxic drug Doxorubicin in microscopic slices from in vivo treated animals. A fluorescent conjugate of different fluorescence, Blankophor-G-Dextran, which remained in the vessels, was used in the same living animals to characterize the vascular supply in the kidney of treated mice in relation to Doxorubicin distribution. PMID- 2578146 TI - An improved method to determine cell viability by simultaneous staining with fluorescein diacetate-propidium iodide. AB - A rapid, simultaneous double-staining procedure using fluorescein diacetate (FDA) and propidium iodide (PI) is described for use in the determination of cell viability in cell suspension. Air-dried slide preparations can be made from the cell suspensions so that an accurate estimate of the viability of the cells in the original suspension can be made up to 1 week later. Viable cells fluoresce bright green, while nonviable cells are bright red. Furthermore, when FDA-PI staining is compared to trypan blue dye exclusion as a method to determine cell viability, FDA-PI is found to be more consistent over prolonged periods of exposure to the dyes. Therefore, double staining with FDA-PI is a rapid, convenient, and reliable method to determine cell viability. PMID- 2578147 TI - Stimulated rat T cell-derived inhibitory factor for cellular DNA synthesis (STIF). II. Kinetics of the production and characterization of the producer. AB - Kinetics of the production of a stimulated T cell-derived inhibitory factor for cellular DNA synthesis (STIF) (1) from Con A-stimulated SD rat spleen cells, and the cells involved in the production of the factor, were examined comparatively with those of interleukin 2 (IL 2) and interferon (IFN). STIF activity in the culture supernatants reached a plateau 24 hr after the culture, and the plateau level was maintained during an additional culture for 72 hr. Characterization of the cells involved in STIF production by means of negative selection of unfractionated or nylon-fractionated spleen cells with anti-rat T cell serum or monoclonal antibodies plus complement revealed that the cells are nylon nonadherent T cells bearing a suppressor T cell marker. The nylon-nonadherent T cell population did not require additional macrophages for STIF production. In vivo pretreatment of rats with cyclophosphamide (25 to 100 mg/kg) reduced or abolished the production of STIF from the Con A-stimulated spleen cells of the rats. The STIF production from Con A-stimulated spleen cells was inhibited by the addition of indomethacin at 10 ng/ml, indicating a regulatory role of prostaglandin(s) in STIF production. The above characteristics distinguish a T cell subset for STIF production from those for IL 2 and IFN production. PMID- 2578149 TI - Co-expression of an epitope on human free kappa-light chains and on a cytoplasmic component in activated T cells. AB - K-1-21 is a murine monoclonal antibody that reacts with human kappa-light chains in free form but not when they are associated with immunoglobulin heavy chains. K 1-21 was unexpectedly shown to bind to a determinant, STA (Sezary T cell antigen), detected by immunofluorescence in the cytoplasm but not on the surface of Sezary T cells isolated from peripheral blood (4/4 cases) and in Sezary T cells from lymph node and bone marrow (one patient). STA was detected in F2/F7, CCRF-CEM, Molt-4, and CCRF-HSB (four human T ALL cell lines), in JURKAT (a human T cell leukemia line), and in MLA144 (a Gibbon T cell lymphoma line). It also occurred in Leu-3a+ antigen-specific T cell clones (6/6 tested). Moreover, although STA was absent from freshly isolated normal T cells, its expression could be evoked in E+ cells from peripheral blood by in vitro culture with phytohemagglutinin. Thus, STA appears to be a cytoplasmic marker for activated T cells. Cytoplasmic inhibition immunofluorescence studies indicated that K-1-21 binding to STA in Sezary cells or T cell lines was inhibited by preincubation of the K-1-21 antibody with purified kappa-Bence Jones protein. STA from radiolabeled MLA144 cell lysates was immunoprecipitated by K-1-21 and was identified on polyacrylamide gel electrophoresis under reducing conditions as a protein of m.w. 57,000. Additional experiments are underway to define the molecular basis of the interesting cross-reactivity between a determinant in T cells and the K-1-21 reactive epitope on free kappa-light chains. PMID- 2578148 TI - Natural killer (NK) cell activating factor released from murine thymocytes stimulated with an anti-tumor streptococcal preparation, OK-432. AB - Natural killer (NK) activity of mouse splenocytes was significantly augmented when the splenocytes were incubated for 3 to 4 hr with culture supernatants of mouse thymocytes stimulated by OK-432, an antitumor preparation from the Streptococcus pyogenes SU-strain. Antiviral activity was also detected in the culture supernatants, but IL 2 activity was not. When the culture supernatants of thymocytes stimulated by OK-432 were fractionated on a column of Blue Sepharose CL-6B, NK enhancing activity and antiviral activity were observed in partly overlapping fractions that bound to the column. However, the antiviral activity in the Blue Sepharose-bound fraction was neutralized completely by treatment with anti-IFN (alpha, beta) antiserum, whereas significant NK cell enhancing activity was still observed after treatment with anti-IFN (alpha, beta) antiserum. When the Blue Sepharose-bound fraction was subjected to gel filtration, the NK cell enhancing activity was detected in the 25,000 to 35,000 and 40,000 to 67,000 m.w. regions, but antiviral activity was observed in the over 67,000 m.w. region. These results indicate that a new kind of lymphokine, called natural killer cell activating factor (NKAF), distinct from IFN and IL 2, was found. The NKAF was found to have the following properties: its pI value is between pH 5.5 and 6.5, it binds to concanavalin A- and lentil agglutinin-Sepharose, and it is stable with pH 2-24 hr treatment. In addition, NKAF-producing cells were peanut agglutinin (PNA)-thymocytes when thymocytes were fractionated by the agglutination-sedimentation method with the use of PNA. PMID- 2578151 TI - Modulation of cytoplasmic calcium in human platelets by the phospholipid platelet activating factor 1-O-alkyl-2-acetyl-SN-glycero-3-phosphorylcholine. AB - The calcium-sensitive, fluorescent dye Quin 2 was used to quantitate changes in free intracellular calcium [( Ca2+]i) induced in platelets by the phospholipid platelet-activating factor 1-O-alkyl-2-acetyl-SN-glycero-3-phosphorylcholine (AGEPC). The Ca2+]i of unstimulated platelets was 91 +/- 18 nM (mean +/- SD, n = 8), and treatment with 1 to 16 nM AGEPC increased [Ca2+]i in a dose-related manner, with 16 nM AGEPC increasing [Ca2+]i by 102 +/- 20 nM. [Ca2+]i was not increased by analogs of AGEPC which do not activate platelets including the lysophospholipid precursor of AGEPC, the optical isomer, and a C-2 benzoyl analog. The capacity of AGEPC to increase [Ca2+]i exceeded that required to induce maximal platelet aggregation. In four experiments, 100% platelet aggregation was induced by 4.5 +/- 2.4 nM AGEPC (mean +/- SD) and was associated with a submaximal increase in [Ca2+]i of 56 +/- 22 nM. Pretreatment of platelets with AGEPC rendered the platelets specifically unresponsive to repeat stimulation with AGEPC in terms of both platelet aggregation and increased [Ca2+]i, whereas the platelet response to thrombin was undiminished by pretreatment with AGEPC. In contrast, the platelet response to 0.5 microM calcium ionophore A23187 was undiminished by pretreatment with the same concentration of ionophore, suggesting that AGEPC does not activate platelets by an ionophore-like mechanism. IgG aggregates and AGEPC in combination activate platelets synergistically, as shown by the observation that a 1-min exposure of platelets to 60 micrograms/ml of IgG aggregates increased the platelet aggregation response to 2 nM AGEPC from 44 to 100%. In contrast, sequential exposure of platelets to IgG aggregates and AGEPC increased [Ca2+]i additively, suggesting that increased [Ca2+]i contributes to but does not fully mediate synergistic platelet activation by IgG aggregates and AGEPC. Quantitation of free intracellular calcium with the fluorescent dye Quin 2 is a highly sensitive technique for delineating the role of calcium in mediating platelet activation. PMID- 2578150 TI - Recognition and display of the predominant idiotype among members of the regulatory circuitry controlling the anti-lysozyme immune response. AB - The in vitro suppression of lysozyme (HEL)-primed helper T cell function (AgTh) is dependent on both suppressor inducer T cells (Tsi) (bearing the Lyt-1 and I-J surface antigens) and suppressor effector T cells (Tse) (bearing the Lyt-2 and I A cell surface antigens). The AgTh and Tsi appear in draining lymph nodes of antigen-primed mice within 10 days of footpad immunization, whereas the Tse is detected in the lymph node around 21 days. Tse are localized to the spleen after i.p. immunization and represent the predominant functional T cell subset. In an attempt to understand the idiotypic relationships that exist among the three T cell types associated with anti-HEL responses in genetic low responder mice, each subset was characterized for expression of the predominant idiotype of anti lysozyme antibodies, IdXL, by treatment with a cytotoxic anti-IdXL antibody and for IdXL-specificity by binding to IdXL-coated plates. Only the Tse was found to bear IdXL. The Tsi, on the other hand, binds to IdXL, and the AgTh belongs to a distinct idiotypic universe. These results suggest that the mode of communication between the Tsi and Tse is via idiotypic complementarity. PMID- 2578153 TI - A monoclonal antibody-based immunoradiometric assay for detection of circulating antigen in Bancroftian filariasis. AB - A monoclonal antibody designated Gib 13 has been used in an immunoradiometric assay (IRMA) to detect circulating antigen in the sera of Wuchereria bancrofti infected subjects from an endemic area of Papua New Guinea. A clear association between the presence of patent infection and the Gib 13 target epitope in serum was established because 93% of microfilaremic individuals were antigen-positive. Moreover, there was a significant correlation between levels of serum antigen and blood microfilarial counts. Detection of circulating antigen in amicrofilaremic subjects with acute symptoms of lymphatic filariasis, and 53% of asymptomatic amicrofilaremic subjects, but not in nonendemic controls, suggests that the Gib 13 IRMA will also be of value in the diagnosis of occult filariasis. However, as in all IRMA based on detection of potentially immunogenic molecules in man, antibodies can be expected to be the major contributor to reduced sensitivity of the assay. PMID- 2578152 TI - Rejection of ticks from guinea pigs by anti-hapten-antibody-mediated degranulation of basophils at cutaneous basophil hypersensitivity sites: role of mediators other than histamine. AB - Previous studies have established that recruitment of basophils to sites of tick feeding in guinea pigs is required to effect immune resistance. In the current study, actively sensitized guinea pigs treated three times daily with H-1 (mepyramine) and H-2 (cimetidine) histamine receptor antagonists, during the challenge tick infestation period, expressed normal resistance to Amblyomma americanum larvae. Similarly, naive guinea pigs treated with anti-histamines four times daily, beginning 7 days before transfer of immune serum and tick challenge and continuing through the tick infestation period, also expressed normal antibody-mediated resistance to A. americanum. These results indicated that histamine was not an important basophil mediator of the resistance response. Ticks allowed to feed on tissue rich in basophils that were induced by sensitization and subsequent local challenge with non-tick protein antigen, keyhole limpet hemocyanin (KLH), expressed normal yield. Ticks that fed on similar tissue rich in basophils induced by sensitization and challenge with KLH, in which the basophils expressed anti-picryl specificity due to systemic passive transfer of anti-picryl antibodies, were rejected when basophils were induced to degranulate by i.v. challenge with picryl antigen at 6 hr (29% rejection), 12 hr (18% rejection), 24 hr (22% rejection), and 48 hr (37% rejection) post-tick attachment. However, basophil degranulation at 18, 72 and 96 hr post-tick attachment had no adverse effect on tick feeding. These hosts were protected from systemic anaphylaxis by treatment with the anti-histamine mepyramine. Release of histamine occurred at tick feeding sites, but vasoactive effects were blocked by mepyramine treatment as evidenced by a lack of increased vascular permeability (bluing) at these sites compared with non-tick-infested tissues, or to cutaneous basophil hypersensitivity (CBH) sites of animals not protected with mepyramine. These results indicate that local recruitment and subsequent degranulation of basophils via immune mechanisms dependent on non-tick antigens can lead to tick rejection, and that basophil-derived mediators other than histamine are involved in this immune resistance response to A. americanum ticks. The identity of the crucial basophil mediator(s) is not known. The significant susceptibility of ticks to basophil-mediator release at 6 to 12 hr and 24 to 48 hr post-attachment coincides with the tick attaching and fast-feeding phases, respectively, suggesting that these phases of tick parasitism are particularly susceptible to the effect of basophil mediators other than histamine. PMID- 2578154 TI - Filarial parasite-specific T cell lines: induction of IgE synthesis. AB - The development of T lymphocyte lines and clones of defined specificity has provided an important method for investigating T cell recognition of foreign antigens as well as T cell influence on B cell activity. We described previously a parasite-specific T cell line (TCL) derived from a patient with a naturally acquired filarial infection and elevated levels of serum IgE. The TCL is composed of Leu-3+ helper cells and is maintained independent of exogenous growth factors. In the present study, we used these T cells to investigate their immunoregulatory function on the in vitro IgE response. These parasite-specific T cells can provide isotype-specific help for antigen-induced IgE production by B cells in vitro. Autologous T cells profoundly suppress IgE production in a concentration dependent manner. Furthermore, soluble factors generated from these filarial specific TCL after antigen stimulation are able to induce the production of IgE in normal human cells not already synthesizing measurable amounts of IgE in vitro. Partial physicochemical characterization of this factor has shown that it is heat labile, has an m.w. between 10,000 and 30,000 M(r), and is a mannose-rich glycoprotein. PMID- 2578155 TI - Monoclonal antibodies to parasite antigens found in the serum of Dirofilaria immitis-infected dogs. AB - We recently reported that parasite antigens are detectable in the serum of Dirofilaria immitis-infected dogs by counterimmunoelectrophoresis (CIE). Hybridoma cell lines that produce monoclonal antibodies specific for these antigens were obtained by immunizing mice with a partially purified antigen preparation, fusing spleen cells with SP-2 myeloma cells, and screening cell culture supernatants for antibody by ELISA and CIE inhibition. Antibodies specific for two epitopes shared by the two major circulating parasite antigens were identified. Immunoperoxidase studies showed that the epitopes recognized by the monoclonals were widely distributed in D. immitis, but the female uterus and eggs were particularly strongly labeled. A monoclonal antibody-based ELISA was developed to measure parasite antigens in dog sera. Parasite antigens were detected in 45 of 46 sera from infected dogs but were absent in sera from uninfected dogs and sera from dogs infected with Dipetalonema reconditum. Serum antigen content was significantly correlated with the number of female worms recovered from infected dogs (r = 0.82, p less than 0.001). Antigenemia was first detected 6 mo after infection, and antigen levels remained fairly stable between 9 and 21 mo after infection. Parasite antigen detection with this monoclonal antibody-based ELISA appears to be superior to previously described diagnostic methods for canine dirofilariasis in terms of sensitivity, specificity, and relation to infection intensity. PMID- 2578156 TI - Epitope-specific antibody response to murine hepatitis virus-4 (strain JHM). AB - Monoclonal hybridoma antibodies to the structural proteins of murine hepatitis virus-4, strain JHM (MHV-4) were used in a competition binding enzyme immunoassay to analyze at the epitope level the antibody response of mice after infection with MHV-4. Colonized mice often had pre-existing MHV antibodies directed against epitopes on the E2 glycoprotein, the E1 glycoprotein, and the nucleocapsid protein. These mice generated a secondary antibody response after virus inoculation, reaching peak levels 7 days after infection. In contrast, Nude/+ mice raised in a pathogen-free colony had no detectable circulating MHV antibodies and generated a primary antibody response which gradually increased to peak levels 14 to 28 days after infection. Kinetics of antibody responses against specific epitopes usually correlated well with measured total virus-specific antibody responses, but variation was observed. Mice injected with three antigenically distinct strains of MHV made antibody responses to conserved epitopes but not to an antigenic determinant absent in these strains. Measurement of epitope-specific responses in a polyclonal population of viral specific antibodies is feasible and a valuable adjunct in understanding viral immunity. PMID- 2578157 TI - Enhancement of tumor growth correlates with suppression of the tumor-specific cytolytic T lymphocyte response in mice chronically infected by Trypanosoma cruzi. AB - The immunity of BALB.B mice to syngeneic Gross murine leukemia virus (MuLV) induced B.GV cells was studied at various times after infection by Trypanosoma cruzi. BALB.B mice chronically infected by the parasite do not develop an effective immune response against B.GV tumor cells, and B.GV tumor growth in vivo is consequently facilitated. The tumor-specific cytolytic T lymphocyte (CTL) compartment in these mice was studied in vitro because CTL are known to participate actively in syngeneic tumor rejection. These analyses showed that: a) CTL differentiation is suppressed in mice with chronic T. cruzi infections; b) suppression is at the level of CTL precursor cell activation; c) suppression is not antigen-specific; and d) suppression is mediated by macrophages and Lyt-2+ T lymphocytes. PMID- 2578158 TI - Is the NK lytic process involved in the mechanism of NK suppression of antibody producing cells? PMID- 2578159 TI - Molecular localization of allogeneic and self determinants recognized by bulk and clonal populations of cytotoxic T cells. AB - The localization of MHC-encoded determinants recognized by hapten- and allo specific cytotoxic T cells was analyzed with the use of cell lines expressing recombinant H-2Dd and H-2Ld MHC products. Bulk cultures of CTL against TNP-self, FITC-self, and AED-self recognized self determinants associated with the N/C1 domains of both Dd and Ld products. A number of allo- and hapten-specific CTL clones were also tested for recognition of the recombinant MHC products. The allo clones specific for Ld or Dd antigens recognized the respective N/C1-associated determinants. In addition, all clones generated against H-2q and known to cross react with H-2Dd antigens recognized determinants associated with the N/C1 associated Dd determinants. Thus, some of the results obtained with CTL parallel, whereas others contrast with, those findings obtained with monoclonal anti-H-2 antibodies. Similar to the observations made with the monoclonal antibodies, no determinant as defined by T cells has been found to be lost as a result of the interaction between the N/C1 and C2/M domains of the Ld and Dd proteins. Nor did our studies detect the presence of new antigens resulting from the interaction of these gene products. However, the present T cell findings continue to contrast previous results demonstrating that antibody interaction with class I products includes recognition of C2/M-associated epitopes. PMID- 2578160 TI - Functional heterogeneity in allospecific cytotoxic T lymphocyte clones. II. Development of syngeneic cytotoxicity in the absence of specific antigenic stimulation. AB - Two out of four long-term murine allospecific cytotoxic T lymphocyte (CTL) clones tested could develop high levels of cytotoxicity against syngeneic target cells when cultured under appropriate conditions. All CTL clones maintained strict allospecificity so long as they were cultured with both appropriate allogeneic stimulator cells and growth factor (supernatant from secondary mixed lymphocyte cultures). In two of the clones, syngeneic reactivity rapidly developed when the allogeneic stimulator cells were replaced with syngeneic or third party stimulator cells, and when the supernatant from EL4 thymoma cells stimulated with phorbol ester was used as growth factor. In addition to killing the appropriate allogeneic target, clones with syngeneic reactivity could kill both syngeneic C57BL/6 targets and H-2-congenic BALB.B targets but not third party unrelated targets, suggesting that the self structure recognized was coded for within the major histocompatibility complex. Such clones did not kill the natural killer (NK) target YAC. The results obtained from cold target inhibition and from subcloning at limiting dilution of clones with syngeneic reactivity suggested that both allogeneic and syngeneic reactivity could be expressed by the same individual cell in the CTL clone. The specificity for syngeneic H-2 as opposed to third party H-2 and NK-sensitive target cells, and the observation that both allospecific and syngeneic killing could be partially blocked by anti-Lyt-2 antibody treatment of the CTL, strongly suggested that different recognition structures are involved in CTL-mediated syngeneic cytotoxicity and NK cytotoxicity. PMID- 2578162 TI - Epidermal cells as accessory cells in the generation of allo-reactive and hapten specific cytotoxic T lymphocyte (CTL) responses. AB - The capacity of epidermal cells (EC) to stimulate T cell activation is a Langerhans cell (LC)-dependent phenomenon. In all in vitro assays probed, LC subserve antigen-presenting cell functions in that they display surface-bound foreign or altered-self structures and thereby activate T cell responses. In contrast, attempts to demonstrate accessory cell (ACC) function of LC-containing EC have yielded negative results, i.e., EC lacking foreign cell surface antigens were not able to restore cytotoxic T lymphocyte (CTL) responses in Ia+ adherent cell-depleted cultures. Reasoning that the ACC function of EC might be critically linked to cluster formation between LC and other cell types involved, we tested the ACC function of EC under experimental conditions that allow a close physical contact between the cell types involved (round-bottomed microtiter plates and brief centrifugation of culture plates). By using these modifications, the failure of highly purified B6 T cells to develop alloreactive CTL activity when stimulated with either highly purified, mitomycin C-treated C3H or B6CF1 T cells was restored by the addition of B6 EC. The CTL thus generated produced significant lysis of Con-A-stimulated C3H or BALB/c, but not B6, spleen cell targets. In a similar fashion, TNP- or FITC-specific CTL were generated when (in a syngeneic system) mitomycin C-treated TNP- or FITC-modified stimulator T cells and responder T cells were co-cultured in the presence, but not in the absence, of unmodified EC. The capacity of EC to restore CTL activity in a culture system depleted of Ia-bearing cells was not dependent upon their H-2 type, but was critically linked to the presence of Ia-bearing LC. We therefore conclude that LC containing EC can subserve the ACC function in the generation of H-2-restricted CTL, provided that culture conditions are chosen that allow a close physical contact between the cell types involved. PMID- 2578161 TI - T cell regulation of antibody responses: an I-A-specific, autoreactive T cell collaborates with antigen-specific helper T cells to promote IgG responses. AB - In earlier studies we showed that hapten-specific inducer T cell clones specifically induce B cells from immunized donors to secrete IgM antibodies. However, IgG responses were not observed, suggesting that an additional signal(s) was required. In this report, we show that an autoreactive T cell clone produces a factor(s) that collaborates with antigen-specific inducer T cells to promote specific IgG responses. This factor is not restricted by antigen or MHC determinants and promotes IgG production both in vivo and in vitro. These findings suggest that autoreactive cells may play an important role in the regulation of isotype expression. PMID- 2578163 TI - Effect of priming with antigen on the expression of C3 receptors on murine B cells and the responses to TI-2 antigens. AB - The effect of priming with DNP-Ficoll on the expression of receptors for the third component of complement (CR) on B cells was studied. B cells from mice primed with antigen were separated into CR- and CR+ populations by rosetting and density gradient centrifugation, and they were examined for antibody responses to TI-2 antigens in vitro. CR- B cells in spleen cells from mice primed with antigen responded well in contrast with the low responsiveness of CR- B cells from unprimed mice. These CR- B cells from primed mice reached their peak responses 1 day earlier than CR+ B cells from primed or unprimed mice. The response of these CR- B cells was specific for the hapten used for priming, and the priming effect was most conspicuous in spleen cells from mice primed with antigen 3 days previously, and it decreased thereafter. The CR- B cells from primed mice also showed better responses than CR+ B cells to all polyclonal B cell activators (PBA) tested. When CR+ B cells were primed in vitro with DNP-Ficoll for 3 days, the major cell population responsive to the antigen in secondary culture was found to be CR- B cells. On the other hand, CR- B cells in spleens could not respond to DNP-Ficoll challenge after in vitro priming with the antigen for 3 days. These results indicate that B cells lose CR by priming with antigen, although they retain their responsiveness to antigens and PBA. The role of CR on B cells in the antibody response is discussed. PMID- 2578164 TI - Non-cross-reactive monoclonal antibodies to human chorionic gonadotropin generated after immunization with a synthetic peptide. AB - Noncross-reactive monoclonal antibodies specific for human chorionic gonadotropin (hCG) were obtained after pre-selection for submolecular specificity with a synthetic peptide immunogen. Mice were immunized with a synthetic peptide representing a segment unique to the beta-subunit of hCG (amino acid residues 109 145), conjugated to diphtheria toxoid. We then derived nine different hybridomas that secreted monoclonal antibodies reactive with both native hCG and isolated C terminal peptide, after somatic cell hybridization of immune spleen cells with a nonsecretory myeloma cell line. None of the nine monoclonal antibodies, termed beta-hCG-CTPa1----a9, reacted with hLH, hFSH, or hTSH, although these pituitary hormones display extensive amino acid sequence homology with hCG. The noncross reactive anti-beta-hCG monoclonal antibodies show apparent association constants on the order of 10(9) to 10(10) M-1. A sandwich-type enzyme-linked immunosorbent assay was set up with cut-off values of around 5 mIU/ml. These antibodies might have important implications for: a) improving the diagnosis and clinical management of pregnancy; b) monitoring the course of development of carcinomas which secrete the hormone, through in vitro assays or in vivo radioimmunodetection; c) evaluating the antibodies' therapeutic potential against such carcinomas; d) studying the biologic functions of the C-terminal segment of beta-hCG; and e) addressing the anti-fertility effect of antibodies raised against that segment. PMID- 2578165 TI - Experimental autoimmune myasthenia gravis: can pretreatment with 125I-labeled receptor prevent functional damage at the neuromuscular junction? AB - Rats were immunized with purified receptor from electric fish to induce experimental autoimmune myasthenia gravis (EAMG). It is implied by the clonal selection theory that antigens react only with receptors on specific immunocompetent cell subpopulations. In an attempt to damage these specific cells with the aid of highly radioactive antigen, one group of rats was pretreated with an additional injection of radiolabeled receptor of high specific activity 3 days before the basic immunization. The success of the immunization was monitored by measuring changes in the following three parameters: antibody titers against nicotinic acetylcholine receptor; number of alpha-bungarotoxin-binding sites at endplates; and number of acetylcholine-operated ionic endplate channels, using quantitative electrophysiologic methods. Conventionally immunized animals showed the classical signs of EAMG: elevated antibody titers against nicotinic acetylcholine receptor and a reduction of the number of alpha-bungarotoxin binding sites, as well as reduction of the number of acetylcholine-operated ionic channels. The same symptoms were found in animals pretreated with unlabeled receptor and in animals pretreated with radioactive albumin. Animals pretreated with radioactively labeled receptor showed far less reduction of functional nicotinic acetylcholine receptor and only slightly raised antibody titers. This study suggests that preimmunization with radioactive antigen selectively eliminates immunocompetent cells, thus precluding the production of antibodies by a subsequent immunization procedure. The same protective effect cannot be obtained by either preimmunization with unlabeled antigen or by radioactively labeled unspecific antigen. PMID- 2578166 TI - Antigenic stimulation regulates the expression of IL 2 receptors in a cytolytic T lymphocyte clone. AB - We have isolated and characterized an H-2Kb-specific CTL clone, B1.8, whose growth is strictly dependent on IL 2 and periodic exposure to stimulator cells. A single, brief encounter with antigen induces on resting B1.8 cells the expression of high-affinity IL 2 receptors, which is maintained for several days, thus allowing cells to undergo at least six rounds of division in the presence of affinity-purified IL 2. We show with the use of monoclonal anti-Lyt-2 or -H-2Kb antibodies, which block specific antigen recognition by B1.8 cells, that continuous antigenic stimulation is not required during this period of growth. After this time, B1.8 cells lose their ability to respond to IL 2 and revert to a resting state, a process that is reversed upon addition of fresh stimulator cells. The decline and subsequent arrest of cell growth correlates with a loss of IL 2 receptors; growth-arrested cells express a 10-fold lower number of receptors than actively growing cells. PMID- 2578167 TI - Comparative effects of various classes of mouse interferons on macrophage activation for tumor cell killing. AB - The effects of mouse interferon-alpha (MuIFN-alpha), -beta (MuIFN-beta), and gamma (MuIFN-gamma) on macrophage activation for tumor cell killing were determined by using proteose peptone-elicited peritoneal macrophages from C3H/HeN and C3H/HeJ mice under conditions that either included or were free of detectable endotoxin. Alone, under the conditions used, none of the interferons was able to activate macrophages directly for tumor cell killing. However, with a second signal provided to responsive macrophages by contaminating endotoxin, added bacterial lipopolysaccharide (LPS), or heat-killed Listeria monocytogenes (HKLM), all three types of interferon induced cytolytic activity, with MuIFN-gamma approximately 500 to 1000-fold more active than either MuIFN-alpha or -beta. Thus, all three interferons were able to prime macrophages for killing but required a second signal before cytolytic activity could be expressed. When MuIFN gamma was mixed with either MuIFN-alpha or -beta and placed on macrophages, little or no killing developed. Mixtures of MuIFN-gamma with either MuIFN-alpha or -beta did increase the sensitivity of macrophages to triggering by LPS, however, compared with macrophages treated with MuIFN-gamma alone. The results are collectively important because they i) confirm that significant quantitative differences exist between the various interferons with regard to their capacity to prime macrophages for tumor cell killing; ii) indicate that to be an efficient activator each type of interferon must be combined with a second stimulus, such as LPS or HKLM; iii) show that neither MuIFN-alpha nor -beta can provide an efficient second triggering signal for macrophages that are primed by MuIFN gamma; and iv) document that mixtures of MuIFN-gamma with either MuIFN-alpha or beta are most efficient at inducing priming, compared with any one of the interferons used alone. PMID- 2578169 TI - Cytokeratin typing of cutaneous tumors: a new immunochemical probe for cellular differentiation and malignant transformation. PMID- 2578168 TI - Bone marrow-derived macrophages: development and regulation of differentiation markers by colony-stimulating factor and interferons. AB - To investigate the role of specific cytokines in the development of the fully mature macrophage, we have employed murine bone marrow cells that were grown in the presence of CSF-1, a colony-stimulating factor that has been shown to induce the proliferation and differentiation of macrophages from their precursor cells. The CSF-1 employed in these studies was partially purified to ensure removal of contaminating interferon (IFN) from the preparations. After 1 to 2 wk in the presence of the partially purified CSF-1, the adherent macrophages were removed from flasks enzymatically and were recultured at known densities in the absence of CSF-1. Cell surface antigens (Mac-1 and Ia) and Fc receptor capacity (as assessed by Fc-mediated phagocytosis) were examined as markers of macrophage differentiation. Basal levels of Fc receptor capacity and Mac-1 antigen were markedly influenced by exposure to CSF-1, and appear to be modulated by CSF induced, macrophage-derived IFN. When the bone marrow-derived macrophages were exposed to exogenous IFN in the absence of CSF-1, they proved to be extremely inducible with respect to Fc-mediated phagocytosis (IFN-beta and rIFN-gamma) and Ia antigen expression (rIFN-gamma) when compared with thioglycollate-elicited macrophages. Thus, macrophage growth factors, such as CSF-1, promote macrophage maturation by inducing the production of autostimulatory signals, such as macrophage-derived IFN. In addition, exogenous cytokine stimuli, such as IFN gamma, further amplify the differentiative potential of these cells. Bone marrow derived macrophages, propagated under well-defined conditions and never exposed to eliciting agents, provide a powerful model for studying the role of cytokines, such as CSF-1 and IFN, in the differentiative pathway of macrophages. PMID- 2578170 TI - Studies on histamine secretion from enzymically dispersed cutaneous mast cells of the rat. AB - A method has been developed for the enzymic dissociation of rat skin into its component cells. The resulting suspensions contained 3-5% mast cells. The latter were intact as judged by light microscopy and exhibited a low spontaneous release of histamine. Cells obtained from actively sensitized animals released histamine on challenge with specific antigen. The process was rapid, being essentially complete within 1 min, and was both calcium-and temperature-dependent. The cells also responded to antirat IgE and to calcium ionophores but showed a selective, time-dependent reactivity toward defined chemical histamine liberators. On the basis of these results the properties of the cutaneous mast cell are compared with those previously reported for mastocytes from other sources and discussed in terms of the general heterogeneity of this cell population. PMID- 2578171 TI - Cells of extramammary Paget's disease express cytokeratins different from those of epidermal cells. AB - The patterns of expression of cytokeratin polypeptides which are closely correlated to routes of differentiation of epithelial cells were studied in extramammary Paget's disease. Cytokeratins of uninvolved and involved epidermis were analyzed by two-dimensional gel electrophoresis of microdissected tissue preparations as well as by immunofluorescence microscopy using cytokeratin antibodies with different specificities. In uninvolved epidermis, cytokeratins Nos. 1, 5, 6, 10, 11, 14, and 16, characteristic of keratinocytes, were found. Epidermis infiltrated by Paget's cells contained the same components and, in addition, cytokeratins Nos. 7, 8, 18, and 19, the latter being characteristic of simple and glandular epithelia, including apocrine and eccrine skin glands. By immunohistochemistry, broad-spectrum antibodies to cytokeratins decorated both keratinocytes and Paget's cells. Antibodies selective for cytokeratins Nos. 1, 10, and 11 stained suprabasal keratinocytes but not Paget's cells. In contrast, antibodies to cytokeratin No. 18 were negative on keratinocytes but the Paget's cells were selectively stained, as were the secretory cells but not the ductal cells in apocrine and eccrine glands. The results show that the cytoskeleton of Paget's cells is different from that of keratinocytes and ductal cells of skin glands and suggest that these tumor cells express the glandular type cytokeratins Nos. 7, 8, 18, and 19. This provides cell biologic support for a relationship of cells of Paget's disease to secretory cells of apocrine and eccrine glands. The histogenesis of extramammary Paget's cells is discussed in relation to these findings. PMID- 2578173 TI - Ultrastructural localization of keratin proteins in human skin using low temperature embedding and the protein A-gold technique. AB - Human skin was embedded in Lowicryl K4M and keratin proteins were localized by incubation with antikeratin antisera, followed by protein A-gold. The antikeratin antisera labeled all intermediate filament (tonofilament) structures in all layers of the epidermis. The association of keratin filaments with hemidesmosomes, desmosomes, and keratohyaline granules was clearly visualized. Desmosomes and keratohyaline granules were not labeled by the antikeratin antisera. No nonfilamentous structures were labeled. The technique described is suitable for studying the distribution of keratin filaments in normal and diseased tissue. PMID- 2578172 TI - Interferon enhancement of HLA-DR antigen expression on epidermal Langerhans cells. AB - Langerhans cells (LCs) are dendritic epidermal cells whose ability to function as accessory/stimulatory cells in initiating the immune response is, like that of macrophages, dependent on the expression of class II major histocompatibility antigens. In normal human skin approximately 50% of LCs identified by cell surface T6 antigenicity also express HLA-DR histocompability determinants. We report here that recombinant DNA-derived human interferon (IFN)-gamma, but not IFN-alpha 2, induces the expression of HLA-DR antigens by the population of human epidermal LCs on which such antigens normally are not detected. IFN-gamma effectively induced HLA-DR on both neonatal and adult epidermal LCs and such induction was blocked by neutralization with a murine monoclonal antibody to IFN gamma. IFN-gamma induction of LC HLA-DR expression is inhibited by prostaglandin E2 (PGE2) and is mimicked by the presence of fatty acid cyclooxygenase inhibitors, known to reduce PGE2 production. These results suggest that IFN-gamma may play a role in regulating skin-associated immune responses through enhanced expression of HLA-DR antigens on LCs and that such enhancement may be mediated by alterations in arachidonic acid metabolism. PMID- 2578175 TI - Phagocytosis, chemiluminescence, and cell volume of alveolar macrophages from neonatal and adult pigs. AB - Broncho-alveolar cells lavaged from the lungs of 1- and 7-day-old piglets and adult pigs were examined to determine their alveolar macrophage content, cell size, and ability to phagocytyze emulsified oil droplets and to chemiluminesce in response to opsonized zymosan particles. Alveolar macrophages were identified by specific cytochemical stains and differential cell counts as being 95%, 97%, and 90% of the cell populations, respectively. The cell volume of macrophages from 1 day-old pigs was 383 +/- 40 microns3; while the cell volumes from 7 day and adult pigs were 1,660 +/- 265 and 1,411 +/- 310 microns3. Alveolar macrophage from 1 day-old piglets possessed little ability to engulf oil droplets; however, macrophages from 7-day-old piglets phagocytized these opsonized droplets at a rate equivalent to alveolar macrophages obtained from adult pigs. The phagocytosis of oil droplets by both 7-day and adult alveolar macrophages manifested similar characteristics. Both rates can be described by saturation kinetics, and while temperatures from 37 degrees to 30 degrees C had little effect, the rate declined rapidly between 30 degrees and 16 degrees C. Alveolar macrophages from 1-day-old piglets displayed a lower magnitude of chemiluminescence than cells from 7-day-old and adult pigs and did not always respond to zymosan exposure. On the other hand, 7-day-old and adult pig alveolar macrophages were quite similar in their ability to chemiluminesce. Increasing extracellular glucose from 1 to 20 mM induced a concomitant increase in chemiluminescence. The findings suggest that functionally competent alveolar macrophages emerge in the pig lung approximately 1 week after birth. PMID- 2578174 TI - Secretion of macrophage-derived growth factor during acute lung injury induced by bleomycin. AB - Monocytes are capable of producing a growth factor which causes fibroblasts to replicate in vitro. This macrophage-derived growth factor (MDGF) may be particularly important in controlling the proliferation of mesenchymal cells in the pulmonary interstitium following acute lung injury. To evaluate the role of macrophages in modulating the proliferative capacity of fibroblasts, we added serum-free culture medium from lavage-derived rat lung macrophages to confluent monolayers of quiescent adult rat lung fibroblasts and monitored their return to the cell cycle both by 3H-thymidine incorporation and by increases in cell number. Growth factor activity secreted in 24 h by untreated macrophages was compared to that from normal macrophages stimulated in vitro by bacterial lipopolysaccharide (LPS) and from macrophages retrieved from lungs injured by intratracheal administration of bleomycin. Unstimulated macrophages from control animals secreted minimal amounts of MDGF; addition of LPS to normal macrophages increased MDGF secretion 3- to 4-fold. Adherent cells obtained by lung lavage of bleomycin-treated animals spontaneously secreted near maximal levels of nondialyzable MDGF with little further stimulation by LPS. The MDGF secreted by LPS-stimulated control cells and by macrophages retrieved from injured lungs share identical elution profiles from DEAE-Sephacel anionic exchange columns, and heat stability profiles. The substance acts as a competence factor when tested on rat lung fibroblasts. These shared physical and biologic properties suggest that the growth factor secreted by cells lavaged from injured lungs is identical to MDGF secreted in response to LPS. Because MDGF release could not be induced by direct exposure of freshly isolated macrophages to bleomycin, we suggest that augmented release of MDGF is an indirect feature of acute lung injury in this model. PMID- 2578176 TI - Axonal transport of glycoconjugates in the rat visual system. AB - Long-Evans rats at 45 days of age were injected intraocularly with 25 mu Ci of [3H]glucosamine. Incorporation of radioactivity into retinal gangliosides, glycoproteins, and glycosaminoglycans (GAGs) was determined at various times after injection. Portions of all three classes of radioactive macromolecules were committed to rapid axonal transport in the retinal ganglion cells. With respect to gangliosides about 60% of those synthesized in the retina were retained in that structure, 30% were committed to transport to regions containing the nerve terminal structures (lateral geniculate body and superior colliculus), and about 10% were deposited in stationary structures of the axons (optic nerve and tract). With the exception of ganglioside GD3 the molecular species distribution of gangliosides synthesized in the retina matched that committed to transport. In contrast to gangliosides a smaller fraction of newly synthesized retinal glycoprotein (less than 12% of that synthesized in the retina) was committed to rapid transport to nerve ending regions and only about 0.5% was retained in the nerve and tract. The molecular-weight distribution of glycoproteins committed to transport differed quantitatively from that of the retina. With respect to GAGs an even smaller portion (1-2%) of that synthesized in the retina was committed to rapid transport; of this portion almost all was recovered in nerve terminal containing structures. A constant proportion of each retinal GAG species was transported to the superior colliculus. We suggest that most of the retinal gangliosides are synthesized in neurons and preferentially in ganglion cells (possibly a function of the large surface membrane area supported by these cells). Subcellular fractionation experiments indicated that transported gangliosides, glycoproteins, and GAGs may be preferentially distributed into different subcellular compartments. PMID- 2578177 TI - Regulation of myelination: Schwann cell transition from a myelin-maintaining state to a quiescent state after permanent nerve transection. AB - Permanent nerve transection of the adult rat sciatic nerve forces Schwann cells in the distal nerve segment from a myelin-maintaining to a quiescent state. This transition was followed by serial morphometric evaluation of the percentage fascicular area having myelin (myelin percent of area) in transverse sections of the distal nerve segment and revealed a rapid decline from a normal value of 36.6% to 3.2% by 14 days for the sciatic nerve to less than 1.0% throughout the remaining time course (up to 105 days). No evidence of axonal reentry into the distal nerve segment or new myelin formation was observed at times under 70 days. In some of the distal nerve segments at 70, 90, and 105 days, new myelinated fibers were observed that usually consisted of only a few myelinated fibers at the periphery and in the worst case amounted to 1.6% (myelin percent of area). Radioactive precursor incorporation of [3H]mannose into endoneurial slices at 4 and 7 days after transection revealed two species of the major myelin glycoprotein, P0, with Mr of 28,500 and 27,700. By 14 days after nerve transection, only the 27,700 Mr species remained. Incorporation of [3H]mannose into the 27,700 Mr species increased progressively to 35 days after transection and then began to decline at 70 and 105 days. Alterations in the oligosaccharide structure of this down-regulated myelin glycoprotein accounted for the progressive increase in mannose incorporation. Lectin affinity chromatography of pronase-digested P0 glycopeptides on concanavalin A-Sepharose revealed that the 28,500 Mr species of P0 had the complex-type oligosaccharide as the predominant oligosaccharide structure (92%). In contrast, the high mannose-type oligosaccharide was the predominate structure for the 27,700 Mr form, which increased to 70% of the total radioactivity by 35 days after nerve transection. Since the biosynthesis of the complex-type oligosaccharide chains on glycoproteins involves high mannose-type intermediates, the mechanism of down regulation in the biosynthesis of this major myelin glycoprotein, therefore, results in a biosynthetic switch from the complex-type oligosaccharide structure as an end product to the predominantly high mannose-type oligosaccharide structure as a biosynthetic intermediate. This biosynthetic switch occurs gradually between 7 and 14 days after nerve transection and likely reflects a decreased rate of processing through the Golgi apparatus. It remains to be determined if the high mannose-type oligosaccharide chain on P0 can undergo additional processing steps in this permanent nerve transection model. PMID- 2578179 TI - Determinants of deoxyglucose uptake in cultured astrocytes: the role of the sodium pump. AB - Glucose utilization in primary cell cultures of mouse cerebral astrocytes was studied by measuring uptake of tracer concentrations of [3H]2-deoxyglucose ([3H]2 DG). The resting rate of glucose utilization, estimated at an extracellular K+ concentration ([K+]o) of 5.4 mM, was high (7.5 nmol glucose/mg protein/min) and was similar in morphologically undifferentiated and "differentiated" (dibutyryl cyclic AMP-pretreated) cultures. Resting uptake of [3H]2-DG was depressed by ouabain, by reducing [K+]o, and by cooling. These observations suggest that resting glucose utilization in astrocytes was dependent on sodium pump activity. Sodium pump-dependent uptake in 2-3-week-old cultures was about 50% of total [3H]2-DG uptake but this fraction declined with culture age from 1 to 5 weeks. Uptake was not affected by changes in extracellular bicarbonate concentration ([HCO3-]o) in the range of 5-50 mM but was significantly reduced in bicarbonate free solution. At high [HCO3-]o (50 mM) uptake was insensitive to pH (pH 6-8), whereas at low [HCO3-]o (less than 5 mM) uptake was markedly pH-dependent. Elevation of [K+]o from 2.3 mM to 14.2-20 mM (corresponding to extremes of the physiological range of [K+]o) resulted in a 35-43% increase in [3H]2-DG uptake that was not affected by culture age or by morphological differentiation. Our results indicate a high apparent rate of glucose utilization in astrocytes. This rate is dynamically responsive to changes in extracellular K+ concentration in the physiological range and is partially dependent on sodium pump activity. PMID- 2578178 TI - Quinolinic acid phosphoribosyltransferase in rat brain. AB - Because of the possible participation of quinolinic acid in brain function and/or dysfunction, the characteristics of its catabolic enzyme, quinolinic acid phosphoribosyltransferase (QPRTase; EC 2.4.2.19), were examined in rat brain tissue. For this purpose, a sensitive radiochemical assay method, based on the conversion of quinolinic acid to nicotinic acid mononucleotide (NAMN), was developed. For brain QPRTase, the Mg2+ dependency, substrate specificity, and optimal assay conditions were virtually identical to those of the liver enzyme. Kinetic analyses of brain QPRTase revealed a Km of 3.17 +/- 0.30 microM for quinolinic acid and Km = 65.13 +/- 13.74 microM for the cosubstrate phosphoribosylpyrophosphate. The respective Vmax values were: 0.91 +/- 0.08 pmol NAMN/h/mg tissue for quinolinic acid and 11.65 +/- 1.55 fmol NAMN/h/mg tissue for phosphoribosylpyrophosphate. All kinetic parameters measured for the brain enzyme were significantly different from those determined for liver QPRTase, indicating structural differences or distinct regulatory processes for the brain and liver enzymes. Phthalic acid was a potent competitive inhibitor of brain QPRTase. Examination of the regional distribution of QPRTase in the rat CNS and retina indicated a greater than 20-fold difference between the area displaying the highest activity (olfactory bulb) and those of only moderate activity (frontal cortex, striatum, retina, hippo-campus). Enzyme activity was present at the earliest age tested, 2 days, and tended to increase in older animals. Brain QPRTase activity was preferentially located in the nerve-ending (synaptosomal) fraction. Enzyme activity was stable over extensive periods of storage at -80 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578180 TI - Influence on 5-[3H]hydroxytryptamine binding site development in chick embryo by serotonergic compounds. AB - Saturable and specific binding sites for 5-[3H]hydroxytryptamine (5-HT, serotonin) characterized by a KD of 3.5-4.5 nM were detected in the chick embryo brain and were shown to develop linearly as a function of age, weight, and protein content. Saturation and displacement studies using unlabeled 5-HT as the displacing ligand suggested a single population of binding sites. However, displacement studies using 5-methoxytryptamine, lysergic acid diethylamide (LSD), 2-bromo-lysergic acid diethylamide (BOL), methysergide, and spiperone as competing ligands suggested the existence of subclasses of [3H]5-HT binding sites because the Hill coefficients were less than unity. When compared with the reported [3H]5-HT binding sites (5-HT1) in the rat forebrain, the IC50 values of the competing ligands were similar. However, the Hill coefficients for LSD and methysergide were less than unity which suggested that the [3H]5-HT binding sites in the chick embryo brain may be more similar to those found in rat spinal cord than rat forebrain. To study [3H]5-HT binding site regulation and development, various serotonergic compounds were injected into the chorioallantoic fluid of the eggs at different times during embryonic development. Multiple pretreatments with d,l-5-hydroxytryptophan, 5-HT, or BOL were found to have no significant effects on either the affinity (KD) or number (Bmax) of specific [3H]5-HT binding sites. Multiple pretreatments with p-chlorophenylalanine were found to increase the Bmax of specific [3H]5-HT binding by 23% (p less than 0.01) whereas multiple pretreatments with LSD were found to decrease the Bmax of specific binding by 45% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578181 TI - Polymorphism of pseudocholinesterase in Torpedo marmorata tissues: comparative study of the catalytic and molecular properties of this enzyme with acetylcholinesterase. AB - We report the existence, in Torpedo marmorata tissues, of a cholinesterase species (sensitive to 10(-5) M eserine) that differs from acetylcholinesterase (AChE, EC 3.1.1.7) in several respects: (a) The enzyme hydrolyzes butyrylthiocholine (BuSCh) at about 30% of the rate at which it hydrolyzes acetylthiocholine (AcSCh), whereas Torpedo AChE does not show any activity on BuSCh. (b) It is not inhibited by 10(-5) M BW 284C51, but rapidly inactivated by 10(-8) M diisopropylfluorophosphonate. (c) It does not exhibit inhibition by excess substrate up to 5 X 10(-3) M AcSCh. (d) It does not cross-react with anti AChE antibodies raised against purified Torpedo AChE. This enzyme is obviously homologous to the "nonspecific" or pseudocholinesterase (pseudo-ChE, EC 3.1.1.8) that exists in other species, although it is closer to "true" AChE than classic pseudo-ChE in several respects. Thus, it shows the highest Vmax with acetyl-, and not propionyl- or butyrylthiocholine, and it is not specifically sensitive to ethopropazine. Pseudo-ChE is apparently absent from the electric organs, but represents the only cholinesterase species in the heart ventricle. Pseudo-ChE and AChE coexist in the spinal cord and in blood plasma, where they contribute to AcSCh hydrolysis in comparable proportions. Pseudo-ChE exists in several molecular forms, including collagen-tailed forms, which can be considered as homologous to those of AChE. In the heart the major component of pseudo-ChE appears to be a soluble monomeric form (G1). This form is inactivated by Triton X 100 within days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578183 TI - Axoplasmic transport and turnaround of neurotoxic esterase in hen sciatic nerve. AB - We have recently found that there is a proximo-distal delay in the recovery of neurotoxic esterase (NTE) following inhibition along the sciatic nerve of the hen. To determine whether this delay could be due to a requirement for the transport of newly synthesized NTE from the cell body, we investigated the transport of NTE by measuring the rate of accumulation of activity at either one or two ligations. Although rapid turnaround of accumulated protein confounds calculation of the transport rate, it appeared that NTE is transported down the hen sciatic nerve at a rate close to 300 mm/day. Acetylcholinesterase (AChE) was found to be transported at a rate of about 500 mm/day, which is close to the expected rate of fast axoplasmic transport in the chicken. The relatively rapid turnaround of NTE compared with the retrograde transport rate precluded the estimation of a retrograde transport rate. A model is presented that accounts for turnaround as a result of exchange between mobile and stationary transport pools. Exchange of NTE between pools may account for the rapid turnaround of NTE described in this paper and for the proximo-distal delay in recovery as a dilution of newly synthesized NTE in the anterograde fast transport pool by inhibited protein as it travels down the nerve. PMID- 2578182 TI - Temporal profiles of proteins responsive to transient ischemia. AB - The responses of long and short half-lived proteins to ischemia were measured in rat brain during 6 days of recovery from 30 min of transient forebrain ischemia produced by four-vessel occlusion. At the end of the ischemic interval, the neocortical activities of four vulnerable enzymes [ornithine (ODC) and S adenosylmethionine (SAMDC) decarboxylases, and RNA polymerases I and II] were unchanged, but within 30 min of reperfusion, their activities dropped by 25-50%. The loss of substance P in the striatum and substantia nigra was slower, reaching about 50% by 12 h. On the other hand, the activities of 5 long half-lived enzymes did not change in the neocortex at 5 and 15 h of reperfusion and regional protein concentrations were essentially unaffected over 6 days survival. The rate and extent of normalization of the amounts or activities of the vulnerable proteins varied. RNA polymerase II and ODC activities were restored within 4 h, and ODC showed a biphasic increase in activity, with peaks at 10 h and 2-3 days. RNA polymerase I and SAMDC activities were restored by 18 h and 5 days, respectively, whereas substance P concentrations did not completely recover, even at 6-15 days. The greater the regional reduction of blood flow during ischemia, the larger the net change (gain or loss) of SAMDC or ODC activity and the longer the time required to normalize the activities of these enzymes. The average rate of proteolysis, assessed by measuring the rate of clearance of 14C from protein prelabeled with [14C]bicarbonate, was abnormal during the first 2 days of reperfusion. Postischemic changes in both protein synthesis and degradation could affect the amounts of some of the proteins responsive to transient ischemia. PMID- 2578184 TI - Sites in myelin basic protein that react with monoclonal antibodies. AB - The epitopes (antigenic sites) for seven monoclonal antibodies (MAbs) evoked in rats or mice by guinea pig or monkey myelin basic protein (BP) have been located in four different sequences of the BPs extracted from various species. Six of the MAbs were evoked by guinea pig BP. (1) One epitope, possibly a pair, is included within residues 1-14 of all BPs tested and reacts with two rat IgG MAbs. (2) A definite pair of overlapping epitopes includes the central Phe91-Phe92 sequence. One epitope is contained entirely within sequence 90-99 and reacts with a rat IgG MAb. The substitution of Ser in chicken BP for Thr97 destroys this epitope. The other epitope appears to include residues on the amino side of Phe44 and even of His32 and suggests some tertiary structure in BP. This epitope reacts with a mouse IgM MAb that does not recognize the chicken substitution. (3) The third epitope lies within residues 114-121, specifically including Trp118, and reacts with a rat IgG MAb. A cross-reacting epitope probably includes residues 44-45 in certain species (guinea pig and bovine but not rabbit). (4) Another pair of epitopes is located within residues 131-140 but is severely species-restricted. This region in guinea pig BP evoked a species-specific mouse IgM MAb. The same region in monkey BP evoked the seventh MAb, a mouse IgG, which reacts with human, chimpanzee, monkey, bovine, and rat-18.5 kDa BPs and to a lesser extent rabbit BP but not with guinea pig, pig, or chicken BPs. Some tertiary structure in guinea pig BP is also suggested by the reactivities with the IgM MAb. All of the MAbs react with myelin in histologic preparations, but the optimum method of preparation of the tissue varies with each. PMID- 2578185 TI - Immunocytochemical studies of substance P and Met-enkephalin in the basal ganglia and substantia nigra in Huntington's, Parkinson's and Alzheimer's diseases. AB - Immunocytochemical studies of the distribution and intensity of Substance P and Met-enkephalin staining in the basal ganglia and substantia nigra were carried out in five cases each of brains from patients with Huntington's disease, Parkinson's disease, Alzheimer's disease, and normal controls. The usefulness of the peroxidase-antiperoxidase method for human autopsy material was confirmed. Substance P and Met-enkephalin fibers were distributed in essentially the same pattern as described in experimental animals and in human brains. In Huntington's disease brains decreased Substance P staining was found in the internal globus pallidus and the substantia nigra, in agreement with radioimmunoassay studies by others. Met-enkephalin staining in the external globus pallidus was of normal intensity, although present within a shrunken area. In Parkinson's and Alzheimer's diseases there was intense immunoreactivity for Substance P in the globus pallidus and substantia nigra, and for Met-enkephalin in the globus pallidus, at variance with reported decreases in Parkinson's disease by radioimmunoassay, but in essential agreement with other immunocytochemical studies. Immunocytochemical methods complement radioimmunoassays of human brain and may help in mapping neuropeptidergic pathways and in pinpointing abnormalities in these pathways in basal ganglia disorders. PMID- 2578186 TI - Specific changes in axonally transported proteins during regeneration of the frog (Xenopus laevis) optic nerve. AB - Labeled proteins in intact and regenerating optic nerves of juvenile Xenopus clawed frogs were examined at three different time points (2 to 4 hr, 18 hr, and 5 to 9 days) following [35S]methionine injection into the eye. The distal axon tips of optic nerves were transected at the margin of the tectal lobe and regeneration of the nerve was followed by three methods: autoradiography, tissue section counting following [3H]proline injection into the eye, and electrophysiological mapping of the visual field projection. By these methods, regrowth was found to occur 2 weeks after transection, but the fibers had not yet sorted their retinotopic pattern. Two-dimensional gel separation of labeled nerve proteins revealed 250 to 300 identifiable proteins, 89 of which (including all spots which differed consistently upon direct comparison of regenerating versus normal nerves) were selected for quantitative treatment. Nine of these spots (240, 135, 65, 64, 58, 54, 56, 31, and 26 kilodaltons) were shown to increase and six (56, 49, 42, 29, 17, and 15 kilodaltons) were shown to decrease significantly in regenerating nerves. By using a crush control and tracking the labeled proteins into the tectum over time, these proteins were shown to be axonally transported proteins. In addition, four other nonaxonally transported proteins also changed during regeneration. PMID- 2578187 TI - Digestibility of native and modified starches: in vitro studies with human and rabbit pancreatic amylases and in vivo studies in rabbits. AB - The effects of cooking and chemical modification of purified starches on the relative rates and extent of their hydrolysis were studied in vitro by using purified human and rabbit pancreatic amylases. Comparison was made with an in vivo study of postprandial glucose and insulin response in adult rabbits. Uncooked starches showed negligible hydrolysis in vitro, whereas cooking (10 min, 100 degrees C) increased both the rate and extent of hydrolysis of all starches. Soluble potato starch was the most and potato amylose the least hydrolyzed. Unmodified tapioca and waxy corn starch were hydrolyzed at the same rate and to the same extent as soluble potato starches. In most cases chemical modification did not change the rate and extent of hydrolysis of the starches. Minor differences between human and rabbit pancreatic amylase exist, but there is a general resemblance between the two amylases in their starch-hydrolyzing properties (correlation coefficient = 0.90; P less than 0.001). The in vivo study showed that uncooked starches elicited no detectable glucose and insulin responses, whereas all the cooked starches except amylose caused glucose and insulin responses comparable to the response seen when feeding glucose. Chemically modified starches (especially waxy corn acetylated distarch adipate) seemed to promote a faster rate of absorption, but the total glucose response (i.e., for the entire 180-min duration) was similar for modified starches and their unmodified counter-parts. The in vivo results showed an overall qualitative similarity to the in vitro results but presented a quantitative difference in the magnitude of the responses for various starch preparations. A good correlation exists between the in vitro and in vivo results (correlation coefficient = 0.84; P less than 0.01). This indicates that the action of pancreatic amylases is an important determinant in the digestion and absorption of these carbohydrates. PMID- 2578188 TI - Inhibition of acid secretion and gastric lesions in rats by the prostanoid Ro 22 6923. AB - The synthetic prostanoid Ro 22-6923 was studied for its ability to inhibit gastric secretion and to protect the gastric mucosa against the injurious effects of stress, indomethacin and ethanol. Ro 22-6923 inhibited basal acid secretion when administered intragastrically or intraduodenally to animals with a gastric fistula. The pH of the gastric juice promptly increased and remained above 5 for 3 h after an intragastric dose of 10 micrograms/kg and the pH remained above 4 for more than 3 h after this dose given intraduodenally. The increase in pH was associated with reduction of acid concentration and H+ output. Ro 22-6923 inhibited histamine-stimulated gastric secretion in a perfused stomach preparation with an ED50 of 15 micrograms/kg compared to values of 43, 126 and 289 micrograms/kg for prostaglandin (PG)E2, ranitidine and cimetidine, respectively. The synthetic prostanoid protected the gastric mucosa from the injurious effects of stress (oral ED50 values of 0.2 and greater than 1.0 mg/kg for Ro 22-6923 and PGE2, respectively) and indomethacin (oral ED50 0.07 and 0.06 mg/kg for Ro 22-6923 and PGE2, respectively). Cimetidine and ranitidine, at high doses, were effective against the mucosal damage produced by stress (ED50 values greater than 100 mg/kg) and indomethacin (ED50 values greater than 10 mg/kg). Ro 22-6923, but not PGE2 or 16, 16-dimethyl PGE2, inhibited dibutyryl cyclic AMP induced [14C]aminopyrine accumulation by isolated parietal cells, indicating that the prostanoid has a direct inhibitory effect on H+ secretion. The results on the antisecretory and cytoprotective properties of Ro 22-6923 suggest this drug could be potentially useful in the pharmacotherapy of peptic ulcer disease. PMID- 2578189 TI - Is antagonism by Bay k 8644 of the negative dromotropic effect of nifedipine pharmacological? AB - The dromotropic effect of Bay k 8644 and its interaction with the negative dromotropic effects of nifedipine, verapamil, MnCl2 and tetrodotoxin were investigated by use of isolated, blood-perfused atrioventricular (AV) node preparations of dogs. These agents were injected into the AV node artery. Single injections of Bay k 8644 (0.1-10 micrograms) shortened AV conduction time, but the decrease remained only about 9 msec at 10 micrograms. This effect was not modified by nadolol. Dose-response curves for the negative dromotropic effect of nifedipine were shifted to the right by about 0.5 log units with infusions of Bay k 8644 into the AV node artery at rates of 3 and 10 micrograms/min. A similar shift of dose-response curves to verapamil occurred at 10 micrograms/min of Bay k 8644. However, Bay k 8644 (3 and 10 micrograms/min) failed to modify dose response curves to MnCl2 and tetrodotoxin. Bay k 8644 (10 micrograms) produced a greater decrease in AV conduction time during the negative dromotropic effect of verapamil (10 or 30 micrograms) and a far greater decrease during the negative dromotropic effect of nifedipine (3 or 10 micrograms) than under control conditions. In contrast, Bay k 8644 (10 micrograms) produced a decrease in AV conduction time nearly to the same extent during the negative dromotropic effect of MnCl2 (10 or 30 mumol) or tetrodotoxin (10 or 30 micrograms) as under control conditions. From these results Bay k 8644 can be described as a rather specific pharmacological antagonist for dihydropyridine slow channel blockers. PMID- 2578190 TI - Synthesis and characterization of selected heteroarotinoids. Pharmacological activity as assessed in vitamin A deficient hamster tracheal organ cultures. Single-crystal X-ray diffraction analysis of 4,4-dimethylthiochroman-6-yl methyl ketone 1,1-dioxide and ethyl (E)-p-[2-(4,4-dimethylthiochroman-6 yl)propenyl]benzoate. AB - There is reported the first four members of heteroarotinoids, the names of which are ethyl (E)-p-[2-(4,4-dimethylthiochroman-6-yl)propenyl]benzoate (1b), ethyl (E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoate (1c), ethyl (E)-p-[2-(4,4 dimethyl-1-oxothiochroman-6-yl)propenyl]benzoate (1d), and (E)-p-[2-(4,4 dimethylchroman-6-yl)propenyl]benzoic acid (1e). IR, 1H NMR and 13C NMR data have been recorded for each compound and support the structural assignments. To provide a firm basis for comparison purposes of future analogues, an X-ray analysis was performed on a single crystal of ethyl (E)-p-[2-(4,4 dimethylthiochroman-6-yl)propenyl]benzoate (1b) and a precursor 4,4 dimethylthiochroman-6-yl methyl ketone 1,1-dioxide (18). These data for the heteroarotinoid 1b revealed that the two aryl ring systems were nearly perpendicular in each of the two molecules present in the unit cell (86.37 degrees and 84.17 degrees, respectively). The space group for both molecules was P1 in triclinic systems. Unit cell dimensions (at 15 degrees C) are as follows: for 1b, a = 20.568 (6) A, b = 14.760 (3) A, c = 7.679 (2) A, alpha = 113.33 (2) degrees, beta = 79.45 (2) degrees, gamma = 79.98 (2) degrees, Z = 4; for 18, a = 9.292 (5) A, b = 9.291 (5) A, c = 7.951 (3) A, alpha = 102.16 (3) degrees, beta = 77.49 (3) degrees, gamma = 79.60 (4) degrees, Z = 2. The sulfur-containing ring is in a distorted half-chair in 1b and the methyl carbon C(12) is shown to be trans to H(13) at the C(11)-C(13) bond. The biological activity of these arotinoids was determined in the tracheal organ culture assay and compared with trans-retinoic acid for ability to reverse keratinization in vitamin A deficient hamsters. The ester 1b displayed activity about one-half log unit less than that of the reference while 1c and 1e had activity nearly one log until less than trans-retinoic acid. The sulfoxide was the least active of the heteroretinoids. PMID- 2578191 TI - The covalent linking of two nucleotide analogues to antibodies. AB - Two anticancer drugs, antagonists of nucleic acids, were covalently linked to antibodies specifically reactive with B leukemia cells and thus with a potential possibility of drug targeting to the tumor site. The drugs cytosine 1-beta-D arabinoside and 5-fluorouridine, competitive inhibitors of enzymes involved in DNA synthesis, were linked to antibodies via a dextran bridge. Cytosine 1-beta-D arabinoside was linked to periodate-oxidized dextran and fluorouridine to dextran hydrazide. The dextran derivatives were in turn linked to antibodies that recognized a specific membrane IgM on B leukemia cells. The drug-antibody conjugates maintained most of the original antigen-binding capacity of the antibody and the full pharmacological activity of the drugs. PMID- 2578192 TI - [1,4]Benzoxazine-2,3-diones as antiallergic agents. AB - The synthesis of a series of [1,4]benzoxazine-2,3-diones and a new class of compounds, benzobisoxazinetetrones, is described. These compounds were evaluated for their effect in the rat mast cell (RMC) test passively sensitized in vitro with rat antiovalbumin serum and for their effect in inhibitory passive cutaneous anaphylaxis (PCA) in the rat. Some of these compounds are of the same potency level as disodium cromglycate in the RMC test and some are effective orally in PCA. PMID- 2578193 TI - Epitopes of herpes simplex virus type 1 glycoprotein gC are clustered in two distinct antigenic sites. AB - Epitopes of herpes simplex virus type 1 (HSV-1) strain KOS glycoprotein gC were identified by using a panel of gC-specific, virus-neutralizing monoclonal antibodies and a series of antigenic variants selected for resistance to neutralization with individual members of the antibody panel. Variants that were resistant to neutralization and expressed an antigenically altered form of gC were designated monoclonal antibody-resistant (mar) mutants. mar mutants were isolated at frequencies of 10(-3) to 10(-5), depending on the antibody used for selection. The epitopes on gC were operationally grouped into antigenic sites by evaluating the patterns of neutralization observed when a panel of 22 antibodies was tested against 22 mar mutants. A minimum of nine epitopes was identified by this process. Three epitopes were assigned to one antigenic site (I), and six were clustered in a second complex site (II) composed of three distinct subsites, IIa, IIb, and IIc. The two antigenic sites were shown to reside in physically distinct domains of the glycoprotein, by radioimmunoprecipitation of truncated forms of gC. These polypeptides lacked portions of the carboxy terminus and ranged in size from approximately one-half that of the wild-type molecule to nearly full size. Antibodies recognizing epitopes in site II immunoprecipitated the entire series of truncated polypeptides and thereby demonstrated that site II resided in the N-terminal half of gC. Antibodies reactive with site I, however, did not immunoprecipitate fragments smaller than at least two-thirds the size of the wild-type polypeptide, suggesting that site I was located in the C-terminal portion. Sites I and II were also shown to be spatially separate on the gC polypeptide by competition enzyme-linked immunosorbent assay with monoclonal antibodies representative of different site I and site II epitopes. PMID- 2578194 TI - Demonstration of three major species of pseudorabies virus glycoproteins and identification of a disulfide-linked glycoprotein complex. AB - The glycoproteins of pseudorabies virus (PRV) Phylaxia were characterized with monoclonal antibodies as specific reagents. Three major structural glycoproteins with molecular weights of 155,000 (155K) (gC), 122K (gA), and 90K (gB) could be identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. We investigated the processing of glycoproteins gA, gB, and gC by in vitro translation, pulse-chase experiments, and in the presence of the ionophore monensin which inhibits glycosylation. gA and gB were found to compose a single polypeptide, whereas gC was found to be a disulfide-linked glycoprotein complex. Immunoprecipitates formed with the aid of anti-gC monoclonal antibodies gave rise to three glycoprotein bands (gC0 [120K], gC1 [67K], and gC2 [58K]) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Limited proteolysis of gC0, gC1, and gC2 resulted in peptide maps of gC0 related to those of both gC1 and gC2. No common peptide bands between gC1 and gC2, however, were seen. We suggest that (i) gC1 and gC2 arise by proteolytic cleavage from the same precursor molecule and stay joined via disulfide bridges and (ii) gC0 is an uncleaved precursor. PMID- 2578195 TI - Analysis of herpesvirus saimiri structural proteins with monoclonal antibodies. AB - Herpesvirus saimiri is a lymphotrophic virus isolated from squirrel monkeys that causes highly malignant lymphomas in owl monkeys, marmosets, and rabbits, but not in its natural host. We have been interested in exploring immunological and biological aspects of this phenomenon and describe in this report the isolation of 27 monoclonal antibodies (MCAs) to herpesvirus saimiri which were grouped into 11 distinct sets based on the proteins they immunoprecipitated. In total, these 11 groups of MCAs identify the majority of the proteins present in the virion. Immunofluorescence was used to study how the viral antigens are compartmentalized in infected cells. One antibody produced intense nuclear staining and immunoprecipitated both the largest protein seen in gels (150,000 daltons) and one of the smallest (13,000 daltons). All of the other groups of MCAs principally stained the cytoplasm of infected cells. One of the unexpected results of this study was the observation that a majority of the MCAs precipitated more than one protein (15 of 27 antibodies, 7 of 11 groups). Whereas one group of MCAs, which normally precipitated four proteins, identified only single polypeptides after dithiothreitol pretreatment, the other sets of antibodies continued to recognize two or more viral antigens under reducing conditions. Immunoprecipitation of viral proteins with polyvalent sera obtained from virus-infected rabbits and monkeys was carried out to verify and extend previously published reports on the proteins of herpesvirus saimiri. PMID- 2578196 TI - RNase H-mediated release of the retrovirus RNA polyadenylate tail during reverse transcription. AB - By examining enzymatic reactions in vitro, we found that an early event during reverse transcription of the avian myeloblastosis virus RNA genome is the release of the 3' polyadenylate tail from the viral RNA template. By using specially constructed molecules containing minus-strand, strong-stop DNA and the 3' end of the viral RNA genome, we found that the reverse transcriptase-associated RNase H is responsible for the endonucleolytic release of polyadenylate. PMID- 2578197 TI - Preliminary characterization of an epitope involved in neutralization and cell attachment that is located on the major bovine rotavirus glycoprotein. AB - The 38,200-molecular weight (unreduced)/41,900-molecular-weight (reduced) glycoprotein of bovine rotavirus, isolate C486, was identified as the major neutralizing antigen. This glycoprotein as well as the corresponding glycoprotein of another bovine rotavirus serotype also specifically attached to cell monolayers under normal conditions for virus adsorption in vitro. Further support for this glycoprotein being directly responsible for virus attachment to cells was that (i) infectious virus of both serotypes could compete with the C486 glycoprotein for cell surface receptors, and (ii) neutralizing monospecific antiserum and neutralizing monoclonal antibodies directed toward the glycoprotein could block this virus-cell interaction. Preliminary epitope mapping of the glycoprotein with monoclonal antibodies further localized the neutralization adsorption domain to a peptide with an approximate molecular weight of 14,000. The effect of two protein modifications, glycosylation and disulfide bridging, on the reactivity of this peptide with antibodies and cell surface receptors was investigated. It was demonstrated that, whereas glycosylation did not appear to affect these reactivities, disulfide bridging seemed to be essential. PMID- 2578199 TI - Small cell lung cancers contain intermediate filaments of the cytokeratin type. PMID- 2578198 TI - Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis: analysis of mutants selected with monoclonal antibodies. AB - With the aid of monoclonal antibodies directed against a specific site on the hemagglutinin-neuraminidase surface glycoprotein, four mutants of the Kilham neurotropic strain of mumps virus were isolated. All four mutants had increased neuraminidase activity. Two mutants (M10 and M12) lost their hemagglutination capacity with human O erythrocytes but retained their ability to agglutinate guinea pig erythrocytes at 4 degrees C. A third mutant (M11) showed a change in the molecular weight of the hemagglutinin-neuraminidase glycoprotein. These three mutants (M10, M11, and M12) showed unaltered capacity to infect tissue cultures and to cause encephalitis in newborn hamsters. A fourth mutant (M13) retained its hemagglutination activity and capacity to infect Vero cell cultures but showed significantly lower neurovirulence in the suckling hamster brain than did the parental Kilham strain and the other three mutants. Both the number of infected neurons and the amount of infectious virus in the brain was reduced. On the other hand, there were no apparent differences in the occurrence of viral antigen in ependymal cells, indicating a selective change in affinity for neurons in the brain. These results suggest that certain changes in the hemagglutinin neuraminidase glycoprotein may lead to an alteration of the neuropathogenicity of the Kilham strain of mumps virus. PMID- 2578200 TI - Reaction of oligodendrocytes and astrocytes to trauma and implantation. A combined autoradiographic and immunohistochemical study. AB - Small excision wounds were made in the parietooccipital cortex of adult mice, and in some of the animals a variety of fetal and adult tissues were implanted into the defect. The response of the oligodendrocytes to trauma and implantation was studied autoradiographically and immunohistochemically and compared to that seen in other glia. The results following trauma alone resembled those seen following implantation. Within 3 days of the surgery a marked proliferative response was seen in mature oligodendrocytes, as judged by uptake of tritiated thymidine in the nuclei, both around the wound and at distant sites extending even into the opposite hemisphere. Labeled astrocytes, microglia (macrophages), and endothelial cells were also found in the same distribution. Immunohistochemical examination using the myelin proteins, myelin basic protein and myelin-associated glycoprotein, failed to show any difference in staining characteristics from normal, in contrast to the marked increase in glial fibrillary acidic protein accompanying the division of astrocytes. The results of this experiment demonstrate that mature oligodendrocytes can proliferate and undergo mitosis in response to nonspecific damage to the central nervous system, in a manner similar to that seen with other glia. This response is, however, not linked to a nonspecific production of myelin proteins, which obviously require some other stimulus for their production. PMID- 2578201 TI - Cytokeratin expression during neoplastic progression of human transitional cell carcinomas as detected by a monoclonal and a polyclonal antibody. AB - Antibodies to intermediate filament proteins were used to study different cell layers in normal human transitional epithelium, 16 human transitional cell carcinomas, and two cell lines derived from human bladder carcinomas. Conventional rabbit antisera to human skin keratins stained all layers of the transitional epithelium from bladder, ureter, and kidney. A slightly higher staining intensity was found in the basal and superficial layers as compared with the intermediate cell layers. A monoclonal antibody to cytokeratin 18 (RGE 53), however, stained only the superficial cell layer of transitional epithelium, the so-called umbrella cells. In well-differentiated (grade I) transitional cell carcinomas, RGE 53 stained only the superficial cells of papillary structures. In higher grade papillary tumors, RGE 53 also stained cells within the basal and intermediate layers, whereas in high-grade, invasive tumors almost all tumor cells were RGE 53 positive. These results show that monoclonal antibodies to cytokeratins can provide both an indication of processes involved in neoplastic progression of bladder tumors and a means of studying the molecular relationship of the tumor cells to normal cells. PMID- 2578202 TI - Dipstick method for human chorionic gonadotropin suitable for emergency use on whole blood and other fluids. PMID- 2578203 TI - Prenatal diagnosis of neural-tube defects with a monoclonal antibody specific for acetylcholinesterase. AB - An immunoassay for acetylcholinesterase (AChE), based on a monoclonal antibody (AE-2), gave the following results when applied to a panel of amniotic fluids: (a) among 651 samples with normal outcome and normal alphafetoprotein (AFP) values there were 2 (0.31%) false positives; (b) of 9 samples with normal outcome and raised AFP values 1 had a raised AChE titre; (c) all 48 samples from anencephaly cases had raised AChE values; (d) among 49 samples from open spina bifida cases (2 of which had normal AFP values), 48 had raised AChE titres. It is suggested that a monoclonal-antibody-based immunoassay may displace polyacrylamide gel electrophoretic analysis of AChE as a complementary test to AFP in prenatal diagnosis of neural-tube defects, since it is a quantitative test largely independent of operator skill and experience. PMID- 2578204 TI - Non-A, non-B hepatitis and intravenous immunoglobulin. PMID- 2578205 TI - Prognostic factors in advanced non-seminomatous germ-cell testicular tumours: results of a multicentre study. Report from the Medical Research Council Working Party on Testicular Tumours. AB - Multivariate analysis of prognostic factors for 458 patients with metastatic non seminomatous germ-cell testicular tumours treated with chemotherapy between 1976 and 1982 in 6 British centres showed a 3-year survival rate of 75%. 3 prognostic groups with survival rates of 91%, 72%, and 47% could be identified by means of tumour volume, serum alphafetoprotein, and human chorionic gonadotropin concentrations. Patient age and year in which the chemotherapy was given were additional variables independently related to outcome. Delay from first symptom to start of treatment was related to tumour volume and marker levels as well as survival time and is an important potentially reversible determinant of long-term survival. This study provides the basis for defining subgroups for future randomised trials and suggests that tumour volume and serum marker levels are important and complementary as prognostic indicators. PMID- 2578206 TI - Interaction of alpha and beta adrenergic stimulation on aortic ornithine decarboxylase activity. AB - The interaction between beta and alpha adrenergic agonists on regulation of cockerel aortic ornithine decarboxylase (ODC) activity was examined. The beta adrenergic agonist isoproterenol both reduced basal aortic ODC activity and prevented induction of the decarboxylase by the alpha adrenergic agonist methoxamine. 3-Isobutyl-1- methylxanthine (IBMX) similarly reduced basal ODC activity and blocked induction of the enzyme by methoxamine. When given ten minutes before or after methoxamine, isoproterenol prevented aortic ODC induction, but not large sustained increases in blood pressure evoked by the alpha adrenergic agonist. In contrast, when injected three hours after methoxamine, isoproterenol had no effect on already elevated levels of enzyme activity. Addition of isoproterenol (10(-7)M), IBMX (1 mM) or dibutyryl cAMP (2.5 mM) to isolated aortic segments cultured in minimal salts-glucose media evoked decreases in basal levels of ODC activity resembling those observed in the intact animal. These results suggest that the balance between alpha and beta adrenergic stimulation may be an important feature of the regulation of polyamine biosynthesis in artery wall cells. PMID- 2578207 TI - Effects of K+-deficiency and serum supplementation on protein turnover and nucleic acid synthesis in HeLa cells. AB - When most of the K+ in a chemically defined medium was replaced with Rb+, cell growth of HeLa cells was strongly inhibited. The growth was partially but significantly restored by an addition of 5% dialyzed calf serum to the medium. The inhibition of cell growth in Rb+-substituted medium was partly due to suppression of protein synthesis by K+ deficiency, but the key mechanism of inhibition is still unknown. Rb+ substitution did not influence protein degradation or nucleic acid synthesis. The restoration of cell growth on addition of serum took place chiefly through stimulation of DNA synthesis. Protein and RNA syntheses were not affected by addition of serum, and serum-induced prevention of protein degradation was less in Rb+-substituted medium than in normal K+ medium. PMID- 2578208 TI - Evidence for an adenosine A2/Ra receptor on human basophils. AB - 5'-N-ethylcarboxamideadenosine (NECA) greater than 2-chloroadenosine greater than adenosine greater than (-)-N6-(R-phenyl-isopropyl)-adenosine greater than (+)-N6 (S-phenylisopropyl)-adenosine, in that order of potency, inhibited in vitro antigen-induced histamine release from human basophils in a dose-dependent fashion. Inhibition occurred only during the first stage of antigen-induced histamine release and the nucleosides failed to inhibit the release caused by the Ca2+ ionophore, A23187. 6-nitrobenzylthioinosine and dipyridamole, which inhibit adenosine uptake, and erythro-9-(2-hydroxy-3-nonyl)adenine, which blocks adenosine metabolism, did not impair the inhibition caused by NECA and adenosine. 8-phenyltheophylline and theophylline, two competitive antagonists of adenosine receptors, blocked the inhibition caused by NECA and adenosine. These data suggest that NECA and other adenosine analogs activate a specific cell surface adenosine receptor which possesses properties similar to those of an adenosine A2/Ra receptor. PMID- 2578210 TI - Management of cancer pain. A practical approach. AB - One in five deaths in Australia is due to cancer. Pain is an important symptom in many of these patients, but it is often either unrelieved or poorly controlled. Misconceptions about the nature of cancer pain and its control are detailed, and the practical management of these patients is discussed in the light of personal experience. Proper use of older therapeutic methods is still important, as recent advances allow better results only in a minority of cases. Special attention is given to the use of regular oral doses of morphine. Many of the interacting factors affecting pain perception are considered, so that the sense of impotence in those faced with the management of a progressive incurable disease may be reduced through an understanding of the causes of pain and its correct management. PMID- 2578209 TI - Electrophysiological and pharmacological evidence that peripheral type benzodiazepine receptors are coupled to calcium channels in the heart. AB - PK 11195, an antagonist of the peripheral type benzodiazepine receptor, does not affect either the duration of the action potential or the tension of the guinea pig papillary muscle. However, it antagonized the effects of the calcium channel blockers, nitrendipine, verapamil, diltiazem, and of BAY K8644, a calcium channel agonist in this heart preparation. On the other hand, PK 11195 does not change the increase in the action potential duration provoked by the potassium channel blocker tetraethylammonium. RO5-4864, an agonist of the peripheral type benzodiazepine receptor, decreased the tension of the guinea pig papillary muscle. The effect was reversed by increasing extracellular Ca2+ concentrations up to 4 mM. These results suggest that in the heart the peripheral type benzodiazepine receptors are coupled to calcium channels. PMID- 2578211 TI - Specific binding of [3H-Tyr8]physalaemin to rat submaxillary gland substance P receptor. AB - [3H]Physalaemin [( 3H]PHY) binds to a single class of noninteracting sites on rat submaxillary gland membranes suspended in high ionic strength media with a KD of 2.7 nM, a Bmax of 240 fmol/mg of protein, and low nonspecific binding. The relative potencies of substance P (SP) and its fragments in competing with [3H]PHY correlate with their relative salivation potencies. This indicates that [3H]PHY interacts with a physiologically relevant SP receptor. In low ionic strength media, the KD of [3H]PHY does not change, but SP and some of its fragments are more potent than PHY in competing with [3H] PHY. Computer-assisted analysis of [3H]PHY and [3H]SP binding in high and low ionic strength media demonstrated that both peptides are equipotent in high ionic strength but that the affinity of SP increases by 70-fold in low ionic strength. The SP fragments that contain a basic residue in positions 1 and/or 3 also display an increased affinity in low ionic strength. These findings document that [3H]PHY binding in high ionic strength (mu = 0.6) accurately reflects the pharmacological potencies of agonists on the SP-P receptor. The binding of [3H]PHY, like that of [3H]SP, increases by the addition of divalent cations (Mg2+ greater than Ca2+ greater than Mn2+). Guanine nucleotides decrease [3H]PHY binding by decreasing the Bmax to the same level (160 fmol/mg of protein), in the presence or absence of Mg2+. PMID- 2578212 TI - Long-term follow-up of asymptomatic healthy subjects with frequent and complex ventricular ectopy. AB - From 1973 to 1983 we followed 73 asymptomatic healthy subjects who were discovered to have frequent and complex ventricular ectopy. Ventricular ectopy in these subjects was measured by 24-hour ambulatory electrocardiography, which showed a mean frequency of 566 ventricular ectopic beats per hour (range, 78 to 1994), with multiform ventricular ectopic beats in 63 per cent, ventricular couplets in 60 per cent, and ventricular tachycardia in 26 per cent. Asymptomatic healthy status was confirmed by extensive noninvasive cardiologic examination, although cardiac catheterization of a subsample of subjects disclosed serious coronary artery disease in 19 per cent. Follow-up for 3.0 to 9.5 years (mean, 6.5) was accomplished in 70 subjects (96 per cent) and documented one sudden death and one death from cancer. Calculation of a standardized mortality ratio (Monson's U.S. data, 8th revision) for 448 person-years of follow-up indicated that 7.4 deaths were expected, whereas 2 occurred (standardized mortality ratio, 27; P less than 0.05). A comparison of survival of the study cohort with that of persons without coronary artery disease or with mild disease, patients with moderate disease, and men with unrecognized myocardial infarction showed a favorable prognosis for the study cohort over 10 years. We conclude that the long term prognosis in asymptomatic healthy subjects with frequent and complex ventricular ectopy is similar to that of the healthy U.S. population and suggests no increased risk of death. PMID- 2578213 TI - Sharing of antigenic determinants between the nicotinic acetylcholine receptor and proteins in Escherichia coli, Proteus vulgaris, and Klebsiella pneumoniae. Possible role in the pathogenesis of myasthenia gravis. PMID- 2578214 TI - Ventricular extrasystoles in healthy subjects. PMID- 2578215 TI - Lipohypertrophy and glomerulonephritis after the use of aprotinin in an insulin dependent diabetic. PMID- 2578216 TI - RNA polymerase heterogeneity in Streptomyces coelicolor. AB - Two forms of RNA polymerase holoenzyme have been identified in the filamentous differentiating bacterium Streptomyces coelicolor. They contain different species of sigma factor and are distinguishable by their ability to recognize different promoter classes. These and other holoenzyme forms may in part determine the selective expression of different gene sets in this morphologically-complex bacterium. PMID- 2578217 TI - Protein kinase C regulation of the receptor-coupled calcium signal in histamine secreting rat basophilic leukaemia cells. AB - It has been proposed that protein kinase C mediates cellular responses evoked by external stimuli, leading to alterations in internal free calcium concentrations. We have shown previously that histamine-secreting rat basophilic leukaemia cells (RBL-2H3), which degranulate on aggregation of the receptors for immunoglobulin IgE, contain a Ca2+- and phospholipid-dependent protein kinase (kinase C). The partially purified enzyme is activated directly by the tumour-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). In intact RBL cells, TPA potentiates histamine release induced by the Ca2+-ionophore A23187 (similar to the synergy reported for platelets, neutrophils and rat peritoneal mast cells). Although TPA at concentrations below 15 nM synergizes with the antigen, higher TPA concentrations inhibit secretion. This selective inhibition suggested that kinase C is involved in both the activation and termination of the secretory process. To examine this possibility, we have determined the effect of TPA on changes in free cytosolic Ca2+ concentration during antigen-induced release. We report here that TPA completely blocks the increase in Ca2+ concentration induced by antigen. Our results strongly suggest that protein kinase C is involved in the regulation of receptor-dependent Ca2+ signalling. PMID- 2578220 TI - Antibodies to myelin basic protein in multiple sclerosis. PMID- 2578218 TI - Functional expression of HLA-DP genes transfected into mouse fibroblasts. AB - The HLA class II antigens are a highly polymorphic family of dimeric cell-surface glycoproteins, expressed predominantly on the surface of immunocompetent cells. They are intimately involved with the induction of the T-cell response to extrinsic antigen and are important predisposing factors for a wide spectrum of autoimmune diseases. We describe here the expression of a class II product from the HLA-DP (new WHO nomenclature, formerly SB) subregion after transfer of cloned genes into mouse fibroblasts. The transfected DP antigen is recognized by several HLA class II monoclonal antibodies and, though present in a mouse cell background, is able to function in the presentation of influenza antigen to cloned DP-restricted human T lymphocytes. PMID- 2578219 TI - Inositol 1,4,5-trisphosphate mimics muscarinic response in Xenopus oocytes. AB - The enhanced metabolism of phosphoinositides, which is associated with a wide variety of stimuli and physiological responses, has been studied intensively. Berridge and his collaborators demonstrated that the first measurable reaction following cell membrane receptor activation is a rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), and that the product of this reaction, inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), could cause a release of non-mitochondrial calcium. These findings have been verified in other systems. Although the relationship between the hydrolysis of PtdIns(4,5)P2 and the mobilization of intracellular calcium was clearly demonstrated, the direct link between Ins(1,4,5)P3 production and the physiological response was only implied. We have investigated the possibility that the intracellular release of Ins(1,4,5)P3 mediates the muscarinic-cholinergic response is Xenopus oocytes, and we show here that intracellularly injected Ins(1,4,5)P3 mimics the muscarinic depolarizing chloride current in Xenopus oocytes. This is the first demonstration of a direct link between phosphoinositides metabolism and a neuro-transmitter induced physiological response. PMID- 2578221 TI - Treatment of dysplasia of the cervical epithelium with an interferon gel. PMID- 2578222 TI - Management of the newborn with myelomeningocele: time for a decision-making process. AB - The relationship between time of surgical intervention and eventual outcome was examined in 110 newborns with myelomeningocele. Numerous earlier reports have cited a significant increase in mortality and morbidity associated with delay of surgery beyond 48 hours. Within the study population of infants, 52 infants (47%) had "early" surgery within the first 48 hours of life, 32 infants (29%) had "delayed" surgery between 3 and 7 days of age, 12 infants (11%) had "late" surgery between 1 week and 10 months of age, and 14 infants (13%) never had surgery by parental decision. Survival rates were similar between those with early, delayed, or late surgery as 92%, 94%, and 100%, respectively, were alive at age 10 months. Also, no significant association existed between time of surgery and development of ventriculitis, developmental delay, or worsening of paralysis. From these observations, it is concluded that there is no urgency in surgical intervention for the initial management of newborns with myelomeningocele. Rather, there is time for comprehensive discussions, counseling, and emotional support for those parents in need of a decision-making process before establishing consent for or against surgical management of their newborn. PMID- 2578223 TI - Development of carbohydrate absorption in the fetus and neonate. AB - Maturation of mechanisms for carbohydrate absorption occurs in a defined sequence during human fetal development. The intestinal enzymes, lactase, sucrase, maltase, isomaltase, and glucoamylase, are at mature levels in the term fetus. Mature levels of pancreatic amylase activity and glucose transport occur postnatally, and levels are low in both the term and preterm neonate. In the preterm infant, sucrase, maltase, and isomaltase are usually fully active, but lactase activity, which increases markedly from 24 to 40 weeks, may be low depending upon fetal age. Despite these developmental patterns, clinical lactose intolerance is uncommon. Postnatal adaptive responses to ingested carbohydrates lead to competent carbohydrate absorption. Inadequately absorbed carbohydrates are salvaged by colonic flora through fermentation of carbohydrates to hydrogen gas and short-chain fatty acids; the latter are readily absorbed by the colon. In this setting, carbohydrate tends to be absent from the stool. Noninvasive reflection of the status of carbohydrate absorption may be obtained from breath hydrogen testing, a technique of particular value in young infants. PMID- 2578224 TI - RNA metabolism in cultures of corneal stromal cells from patients with keratoconus. AB - Total cellular RNA was extracted from cultured keratoconus and normal human corneal stromal cells. The translational activity of these RNAs was examined in a cell-free translation system derived from reticulocyte lysate. Results indicated that keratoconus cells can be separated into two groups, as has been shown previously. Group I keratoconus cells contained the same amount of total RNA as normal cells. RNA activity and the rate of mRNA synthesis in this group of keratoconus cells were also normal. By these criteria it seems that the protein synthesizing system is functioning properly, and group I keratoconus cells should have a normal rate of protein synthesis. These results correlate well with previous findings. Group II keratoconus cells, in contrast, contained more RNA than normal cells. The translational efficiency of RNA was so markedly reduced that the elevation in RNA content did not compensate for the decrease in translational efficiency. It is likely that the reduced protein and collagen synthesis in this group of cells is related to the reduction in the RNA activity. An inhibitory component was present in the keratoconus RNA which affected synthesis of all proteins and suppressed translation of normal RNA. PMID- 2578225 TI - Myosin: a link between streptococci and heart. AB - Murine monoclonal antibodies to Streptococcus pyogenes reacted with skeletal muscle myosin. High molecular weight proteins in extracts of human heart tissue that reacted with an antibody to S. pyogenes also reacted with a monoclonal antibody to ventricular myosin. Adsorption of the antibody to streptococci with S. pyogenes simultaneously removed reactivity of the antibody for either S. pyogenes or myosin. These results indicate that myosin shares immunodeterminants with a component of S. pyogenes. PMID- 2578226 TI - Fluorogenic substrate detection of viable intracellular and extracellular pathogenic protozoa. AB - Viable Leishmania promastigotes and amastigotes were detected by epifluorescence microscopy with fluorescein diacetate being used to mark living parasites and the nucleic acid-binding compound ethidium bromide to stain dead cells. This procedure is superior to other assays because it is faster and detects viable intracellular as well as extracellular Leishmania. Furthermore, destruction of intracellular pathogens by macrophages is more accurately determined with fluorescein diacetate than with other stains. The procedure may have applications in programs to develop drugs and vaccines against protozoa responsible for human and animal disease. PMID- 2578228 TI - The role of hemoglobin denaturation and band 3 clustering in red blood cell aging. AB - As hemoglobin begins to denature, it forms hemichromes that cross-link the major erythrocyte membrane-spanning protein, band 3, into clusters. These clusters provide the recognition site for antibodies directed against senescent cells. These antibodies bind to the aged red cell and trigger its removal from circulation. PMID- 2578227 TI - Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). AB - The nucleotide sequence of molecular clones of DNA from a retrovirus, ARV-2, associated with the acquired immune deficiency syndrome (AIDS) was determined. Proviral DNA of ARV-2 (9737 base pairs) has long terminal repeat structures (636 base pairs) and long open reading frames encoding gag (506 codons), pol (1003 codons), and env (863 codons) genes. Two additional open reading frames were identified. Significant amino acid homology with several other retroviruses was noted in the predicted product of gag and pol, but ARV-2 was as closely related to murine and avian retroviruses as it was to human T-cell leukemia viruses (HTLV I and HTLV-II). By means of an SV-40 vector in transfected simian cells, the cloned gag and env genes of ARV-2 were shown to express viral proteins. PMID- 2578230 TI - Results of an aggressive surgical approach to gastric carcinoma during a twenty three-year period. AB - The early work of Dr. William Longmire with total gastrectomy for gastric carcinoma prompted us to initiate an aggressive surgical approach to gastric carcinoma in 1960: in curative resections radical total gastrectomy with hepaticoceliac-left gastric arterial node dissection was to be performed for tumors involving the entire stomach or upper two thirds and radical 80% to 90% subtotal gastrectomy with similar node dissection for tumors located in the antrum. During a 23-year period 213 patients with confirmed gastric carcinoma were studied. Celiotomy was performed in 192: advanced gastric cancer was found in 185 and seven had early gastric cancer. In only 80 patients could resections for "cure" be done. In 31 patients who underwent total or extended total gastrectomy the operative mortality rate was 9.6%, and life table survival curves show a better survival rate than in 49 patients treated by subtotal gastrectomy, with an operative mortality rate of 16.3%. The study shows the urgent need for diagnosis of early gastric cancer by gastroscopic screening of adults at risk and the meager salvage by radical resection in advanced disease. PMID- 2578229 TI - The surgical treatment of pancreatic carcinoma. AB - This is a report on 501 pancreatic and periampullary cancers treated at the Mannheim Surgical Clinic during the past 11 years. Modern diagnostic measures (computerized axial tomography, endoscopic retrograde cholangiopancreatography, and angiography), while failing to detect the early operable tumors, have contributed to a rise in the rate of resectability of cancers of the pancreatic head (from 5% to 21%). Tactical problems of surgical treatment include the extent of resection required (total or partial), the rationale of preliminary biliary decompression, the symptomatic but unidentified mass in the head of the pancreas, and concomitant celiac artery stenosis. In 118 duodenopancreatectomies performed for cancer and 81 performed for severe and complicated chronic pancreatitis, the operative and hospital mortality rate was 2.5%. Of the 28 patients whose pancreatic resections for cancer occurred more than 5 years ago, 10 reached the 5 year survival limit. PMID- 2578231 TI - Effect of chlordecone (Kepone) on the rat brain concentration of 3-methoxy-4 hydroxyphenylglycol: evidence for a possible involvement of the norepinephrine system in chlordecone-induced tremor. AB - 3-Methoxy-4-hydroxyphenylglycol (MHPG) is the major metabolite of norepinephrine (NE) in the rat brain. A single injection of tremorigenic doses of chlordecone to adult male Fischer-344 rats resulted in significant increases in MHPG concentrations in hypothalamus, brain stem, cerebellum, and caudate nucleus. The increase in MHPG was accompanied by a decrease in NE in the hypothalamus, suggesting that chlordecone treatment caused an increase in the turnover of NE in the brain. There was a dose- and time-related correlation between the increases in the concentrations of MHPG in hypothalamus, brain stem, and cerebellum and tremor in rats. The increase in MHPG in hypothalamus and brain stem occurred as early as 1 hr postdosing; this preceded the earliest measurable sign of tremor and initial hypothermia. Whether the alterations in the brain NE system are involved in the expression of the tremor and the initial hypothermia induced by chlordecone or whether they are merely associated with these changes is not clear. PMID- 2578232 TI - Malondialdehyde-like material and beta-thromboglobulin plasma levels in patients suffering from transient ischemic attacks. AB - Beta-thromboglobulin (betaTG) and malondialdehyde-like material (MDA-LM) plasma levels were studied in patients affected by transient ischemic attacks (TIA) after 2-4 months from the last episode. BetaTG and MDA-LM values were significantly higher in TIA patients than in 20 controls matched for age. No correlation between MDA-LM and betaTG was seen. This study suggests that in vivo platelet activation and, likely, increase of platelet cyclo-oxygenase activity can be detectable in TIA patients. PMID- 2578233 TI - The very low birth weight infant: sensory experience and development. PMID- 2578234 TI - Occurrence of posttransplant donor-specific cell-mediated lympholysis nonreactivity in renal allograft recipients with perioperative transfusions only. PMID- 2578235 TI - The impact of low donor-specific MLR versus HLA-DR compatibility on kidney graft survival. AB - We have analyzed the predictive value on cadaver kidney graft survival of a low stabilized relative response (SRR) in donor-specific mixed lymphocyte culture (MLC). Thirty-eight recipients and donors of cadaver kidneys constituted the case material. The 12-month survival of cadaveric grafts was 83% when the SRR values of the mixed lymphocyte reaction (MLR) between recipient and donor were below or equal to 50 and 40% when the SRR values were above 50. The difference was statistically significant (P less than 0.006). A higher (though not significantly so) graft survival rate was obtained in transplant groups when the recipients and donors were well matched for DR antigens. The 12-month survival was 70% when no DR incompatibilities could be demonstrated and 50% when one or more DR antigens were incompatible. The primary role of MLR matching for the outcome of kidney graft survival is supported by the observation that the influence of the MLR is still significant when stratified for DR matching (P less than 0.05). In conclusion, when adequately stabilized, the specific MLC reactivity of the recipient against the donor is a very important predictive factor for the outcome of cadaver kidney transplantation, which stresses the importance of improvements in serological DR typing. PMID- 2578236 TI - Immune response to ultraviolet-induced tumors. I. Transplantation immunity developing in syngeneic mice in response to progressor ultraviolet-induced tumors. AB - Ultraviolet-light-induced murine skin tumors were analyzed for the ability to induce transplantation immunity and cytotoxic lymphocytes in syngeneic mice. A correlation was found between tumor regression and the induction of cytotoxic T cells with specificity for a unique tumor-associated antigen. Processing tumors possessed tumor-associated transplantation antigens (TATA), which could be demonstrated by transplantation in hyperimmunized mice. Progression correlated with a lack of splenic cytotoxic T cell reactivity. High levels of in situ cytotoxic reactivity could be induced by presenting the tumor-specific antigen on nongrowing tumor cells. Tumor-bearer hosts were shown to be sensitized to TATA because cultured tumor-bearer T cells adoptively transferred protection against tumor outgrowth. Mechanisms of the in vivo suppression of antitumor immunity are discussed. PMID- 2578237 TI - A monoclonal antibody to a formaldehyde-resistant epitope on the nonpolymorphic constant part of the HLA-DR antigens. PMID- 2578238 TI - Monoclonal antibodies to the P protein of Sendai virus define its structure and role in transcription. AB - Four monoclonal antibodies specific for Sendai virus nucleocapsid protein P were used to examine both the antigenic structure of P and its role in transcription. Three distinct antigenic regions were delineated on P by competitive radioimmunoassays (RIAs), and through Western blot analysis all three sites were mapped to a 40,000-MW (40K) Staphylococcus aureus protease V8-digestion fragment, which remains associated with the neucleocapsid structure. To study the function of P, nucleocapsids were treated with saturating amounts of anti-P monoclonal antibodies and it was found that transcription in vitro was inhibited by 60-90%. Data, therefore, are consistent with the conclusion that the P protein is required for transcription and that the 40K protease-resistant core contains the functionally important portion of the molecule. Further analysis of the P structure showed that some of the 40K fragments were linked by disulfide bonds. These results suggest that the protease-resistant 40K fragment is in the carboxyl terminal half of P, since the three cysteine residues of P are found there (C. Giorgi, B. M. Blumberg, and D. Kolakofsky (1983), Cell 35, 829-836). PMID- 2578239 TI - Replication strategy of Kunjin virus: evidence for recycling role of replicative form RNA as template in semiconservative and asymmetric replication. AB - Only three forms of Kunjin virus-specified RNA were isolated from cytoplasm early after the latent period (about 15 hr) viz., 44 S genomic-sized single-stranded RNA, 20 S double-stranded "replicative form" (RF), and 20-28 S partially ribonuclease-resistant (about 70%) "replicative intermediate" (RI). The RF and RI were resolved by electrophoresis in aqueous-agarose gel only following LiCl fractionation. The RI did not enter urea-polyacrylamide gels. After denaturation of untreated or RNase-treated RI and RF, only 44 S RNA was present in electropherograms. RNA polymerase activity at 8 hr postinfection was detected by in vitro assays of cytoplasmic extracts and reached a maximum at 24 hr, the only major labeled product being RF; a trace amount of free 44 S RNA was also produced. These results, and the kinetics of incorporation of [3H]uridine into RI, RF, and 44 S RNA in pulse and pulse-chase experiments, formed the basis of a model in which flavivirus RF functions as a recycling template for semiconservative and (mainly) asymmetric replication, on which only one nascent strand is synthesized per cycle. PMID- 2578241 TI - Torsade de pointes associated with elevated N-acetylprocainamide levels. PMID- 2578240 TI - The requirement of protein synthesis for VSV inhibition of host cell RNA synthesis. AB - Published ultraviolet (uv) inactivation data and in vitro transcription studies have suggested that vesicular stomatitis virus (VSV) leader RNA was solely responsible for the inhibition of host cell RNA synthesis by this virus. Since no protein product is encoded in leader RNA, this conclusion implied that no protein synthesis should be required for this effect. Therefore, the inhibitory activity of VSV was examined in the presence of the protein synthesis inhibitors, cycloheximide, pactamycin, and emetine. Protein synthesis inhibitors are known not to interfere with VSV primary transcription, but in their presence viral replication and amplification of transcription do not take place. Although at 39 degrees the VSV mutant tsG22 could undergo only primary transcription, maximum inhibition of host cell RNA synthesis took place. However, in the presence of the protein synthesis inhibitors the VSV mutant was no longer able to interfere with host cell RNA synthesis. These results could not be explained by a change in the concentration of intracellular leader RNA which remained unaltered by the drugs. Similar results were also obtained with wild-type VSV in the presence of cycloheximide. Upon removal of the drug, inhibition of host cell RNA synthesis was reestablished in parallel with the restoration of protein synthesis. It is concluded that protein synthesis is required for the inhibitory activity of VSV, presumably because the active inhibitory complex is a nucleoprotein containing leader RNA and either a cellular protein or the viral N protein. The cellular protein would have to be in limiting supply since de novo protein synthesis was required for the inhibition to take place. PMID- 2578243 TI - Control of cardiac arrhythmias by selective lengthening of repolarization: theoretic considerations and clinical observations. PMID- 2578242 TI - QT prolongation and arrhythmia suppression. AB - It seems possible to draw some overall conclusions from the data on antiarrhythmic drug-induced QT prolongation and its role in drug effects. At one end of the spectrum are patients with highly exaggerated QT responses during therapy, most often in the setting of hypokalemia and long cycle lengths (post ectopic pauses, bradycardia). These patients may be at high risk for development of arrhythmias during therapy. It should also be remembered that the presence of hypokalemia may render antiarrhythmic agents less effective in general. On the other hand, modest QT prolongation in the course of therapy with an antiarrhythmic drug may well be a marker of reduction of dispersion of action potential durations or refractory periods and hence represent an antiarrhythmic effect. The clinical actions of these drugs in patients with arrhythmias strongly suggest that this is the case. New agents with the ability to reduce dispersion of repolarization or of refractoriness without inducing arrhythmias may well become the agents of choice for the treatment of serious cardiac rhythm disturbances. PMID- 2578244 TI - Polymorphic ventricular tachycardia and ventricular fibrillation due to N-acetyl procainamide. PMID- 2578245 TI - Chronic lorcainide therapy for symptomatic premature ventricular complexes: efficacy, pharmacokinetics and evidence for norlorcainide antiarrhythmic effect. AB - Chronic premature ventricular complexes (PVCs) have been effectively suppressed by oral lorcainide as reported in previous short-term studies. The plasma level effect relation of lorcainide may be affected by the possible cardioactivity of norlorcainide, a metabolite that accumulates after repeated oral doses. This study evaluated the long-term efficacy of lorcainide in suppressing chronic symptomatic PVCs, and examined the relation of arrhythmia suppression to plasma concentrations of lorcainide and norlorcainide. Fourteen patients were treated with lorcainide, 200 to 400 mg/day, 12 of whom achieved nearly complete suppression of arrhythmias after treatment for 1 year. Chronic lorcainide treatment was well tolerated; no patient discontinued treatment because of adverse effects. Lorcainide and norlorcainide plasma concentrations remained stable after the first week of therapy. Antiarrhythmic activity persisted throughout the year. Upon drug withdrawal, the mean lorcainide washout half-life was 14.3 +/- 3.7 hours and the mean norlorcainide washout half-life was 31.9 +/- 8.9 hours. The return of arrhythmias occurred well after the lorcainide plasma concentration had decreased to subtherapeutic levels, suggesting an antiarrhythmic effect of norlorcainide. Thus, long-term lorcainide therapy is effective in treating chronic symptomatic PVCs and is well tolerated by most patients. The metabolite norlorcainide appears to have antiarrhythmic activity independent of lorcainide. PMID- 2578246 TI - Fast Papanicolaou stain. PMID- 2578248 TI - Relationship of ventricular ectopy to nocturnal oxygen desaturation in patients with chronic obstructive pulmonary disease. AB - Sudden death and oxyhemoglobin desaturation are known to occur during sleep in patients with chronic obstructive pulmonary disease. The present study was undertaken to determine the frequency with which nocturnal oxygen desaturation promotes an increase in ventricular ectopic activity, since such a relationship could represent a potential pathophysiologic mechanism for sudden death during sleep. Forty-two clinically stable subjects with moderately severe obstructive airways disease, mean ratio of one-second forced expiratory volume to forced vital capacity = 51 +/- 12 percent, underwent overnight polygraphic sleep study. Oxyhemoglobin saturation was monitored by ear oximetry, and electrocardiographic leads CC5 and CM5 were employed for arrhythmia detection. Premature ventricular complexes were detected in 27 (64 percent) of the subjects and were complex (multifocal, repetitive, or both) in 17. No significant relationship between premature ventricular complex frequency and arterial oxygen saturation was detected for the group as a whole. In part, this result can be attributed to the relatively mild hypoxemic stress experienced by the 22 subjects in whom arterial oxygen saturation remained greater than 80 percent. In contrast, six (30 percent) of the 20 patients who had desaturation to less than 80 percent showed a greater than 150 percent increase in premature ventricular complex frequency with oxygen desaturation. These results suggest that nocturnal hypoxemia, if of sufficient magnitude, is capable of increasing ventricular ectopy during sleep in a substantial number of patients with chronic obstructive pulmonary disease. PMID- 2578247 TI - Nonspecific staining of mast cells by avidin-biotin-peroxidase technic. PMID- 2578249 TI - Heroin: facts and comparisons. PMID- 2578250 TI - Genetic counseling for low maternal serum alpha-fetoprotein. PMID- 2578251 TI - The psychological impact of false positive elevations of maternal serum alpha fetoprotein. AB - The purpose of this study was to assess the psychological impact of maternal serum alpha-fetoprotein screening on pregnant women with false positive elevations of maternal serum alpha-fetoprotein and on their male partners. Subjects with maternal serum alpha-fetoprotein elevations and their partners exhibited significantly heightened anxiety as measured by the State-Trait Anxiety Inventory following notification of the elevation, and this anxiety persisted until normal results were obtained by further testing. Heightened anxiety was not alleviated by counseling prior to definitive testing. Once normal results were obtained, anxiety returned to control levels and heightened anxiety was not observed throughout the remainder of pregnancy. Maternal serum alpha-fetoprotein elevations had little effect on maternal attitudes toward pregnancy as measured by the Maternal Attitudes to Pregnancy Inventory. Similarly, no differences were observed between subjects with normal and elevated maternal serum alpha fetoprotein levels with regard to depression, marital discord, work attendance, or work productivity. PMID- 2578252 TI - Subretinal choroidal neovascularization in birdshot retinochoroidopathy. AB - We studied four eyes of two patients with bilateral birdshot retinochoroidopathy which developed subretinal choroidal neovascular membranes involving the macula. The subretinal choroidal neovascular membranes in our patients developed six months to five years after the onset of the disease. Both patients described decreasing visual acuities at the time when the choroidal neovascular membranes were identified. Adjacent to the classic depigmented areas of birdshot retinochoroidopathy were increased pigmentation, hemorrhage, or fluid indicative of subretinal neovascularization. Fluorescein angiography confirmed the presence and demonstrated the location of these membranes. PMID- 2578253 TI - Electrical activity, cAMP concentration, and insulin release in mouse islets of Langerhans. AB - The influence of forskolin and 3-iso-butyl-1-methylxanthine (IBMX) on mouse pancreatic beta-cell electrical activity, whole islet cAMP content, and insulin release were investigated. The two drugs potentiated to a similar extent both glucose-stimulated electrical activity and insulin release. In terms of the electrical response, both drugs potentiated the silent depolarization of the membrane in response to low (substimulatory) glucose concentrations, whereas at higher (stimulatory) glucose concentrations they caused an increase in the plateau fraction, with a response similar to the effect of increasing the glucose concentration. Both phases of insulin release were increased by each of the drugs. Ten micromolar forskolin and 100 microM IBMX caused an increase in intraislet adenosine 3',5'-cyclic monophosphate (cAMP) in the presence of 11.1 mM glucose, the former a 17-fold and the latter a 2-fold increase over the cAMP concentration in the presence of glucose alone. Because the two drugs lead to an increase in islet cAMP content, it is proposed that protein phosphorylation resulting from an activation of beta-cell cAMP-dependent protein kinases is responsible for the potentiation of the glucose-induced insulin release and beta cell electrical activity. The observed effects on electrical activity are compatible with the hypothesis that cAMP-dependent phosphorylation induces alteration of the kinetics of the calcium-sensitive potassium permeability of the beta-cell plasma membrane. The increase in calcium entry into the beta-cell that would result from these alterations may be responsible for the cAMP-dependent potentiation of insulin release. PMID- 2578254 TI - Oncogenes, ions, and phospholipids. AB - Recent discoveries in tumor virology, lipid biochemistry, and ion transport studies promise to revolutionize our understanding of cell proliferation, differentiation, and tumorigenesis. A model is proposed, based on similar schemes presented recently by others, that incorporates these discoveries and provides a focus for future research on the functions of oncogene proteins. The model suggests that the early (competence) events in the initiation of cell proliferation are triggered by activation of phosphatidylinositol (PI) turnover, which releases two second messengers, 1,2-diacylglycerol (1,2-DG) and inositol 1,4,5-trisphosphate (IP3). PI turnover is proposed to be regulated by the oncogene protein kinases (src, ros, abl, fps) either directly (acting as PI kinases) or indirectly (as tyrosine kinases). The IP3 triggers Ca2+ release from internal stores, and the elevation of cytosolic Ca2+ acts synergistically with 1,2-DG to activate the Ca2+- and phospholipid-dependent kinase C. Kinase C copurifies with the receptor for the tumor-promoting phorbol esters. It is suggested that kinase C then activates the Na+-H+ exchange system, resulting in an elevation of cytosolic pH and Na+, and that these ionic signals (including the change in Ca2+), either in concert or individually, induce further events, including expression of the protooncogene c-myc, which together commit the cell to initiate replication. Evidences in support of this model are reviewed, together with complications indicating its present inadequacies, particularly recent data suggesting that 1,2-DG may activate tyrosine kinases independent of kinase C. PMID- 2578256 TI - Mediation of muscarinic stimulation of pepsinogen secretion in the frog. AB - The in vitro release of pepsinogen secretion by the isolated esophagus of the American bullfrog was studied with an improved model system. The tissue was mounted in a double chamber that preserves mucosal polarity and provides both control and test segments, each 1 cm2 from the same tissue. Pepsinogen secretion was severalfold higher than previously found with mucosal strips and could be sustained for several hours. Bethanechol (BCh) caused concentration-dependent (0.1-50 microM) pepsinogen secretion with a Vmax of 74 +/- 12 micrograms X mg prot-1 X h-1 or 50-60% of total pepsinogen; Km was 3 microM and 500 microM BCh stimulated at less than the Vmax value. Atropine specifically blocked BCh and pA2 = 9.3. In the presence of 100 microM isobutylmethyxanthine, BCh produced a dose dependent increase in tissue cAMP but not cGMP. BCh remained effective in Ca2+ free medium. In calcium-free medium EGTA concentration dependently (0.2-5 mM) suppressed the pepsinogen response to BCh. The evidence thus far suggests that cholinergic stimulation of pepsinogen secretion in the tissue acts via both cAMP and Ca2+. More specific studies would be required for absolute confirmation of either or both apparent mechanisms and to resolve how they interact. PMID- 2578255 TI - Reserpine is a calcium channel antagonist in normal and GH3 rat pituitary cells. AB - Reserpine exerts direct effects on several tissues, including inhibition of hormone release from rat anterior pituitary cells. To test the hypothesis that reserpine may be acting as a calcium channel antagonist, normal or GH3 rat anterior pituitary cells were preincubated in reserpine or the conventional calcium channel blocker, D-600, followed by exposure to 45Ca2+ together with stimulants of calcium uptake: maitotoxin, a potent calcium channel activator; A23187, a calcium ionophore; or 50 mMK+. After incubation, the cells were harvested by vacuum filtration and cell-associated radioactivity determined. In normal cells, reserpine blocked both basal and K+-stimulated calcium uptake. Reserpine selectively blocked maitotoxin but not A23187-induced calcium uptake. In GH3 cells 9 microM reserpine and 30 microM D-600 were equally effective in blocking maitotoxin-stimulated calcium uptake. Reserpine appears to block voltage dependent calcium channels in pituitary cells in a concentration-dependent manner but not calcium uptake caused nonspecifically by A23187. PMID- 2578257 TI - N-terminal fragments of CCK-(26-33) as cholecystokinin receptor antagonists in guinea pig pancreatic acini. AB - In the present study we synthesized different N-terminal fragments and analogues of the C-terminal octapeptide of cholecystokinin [CCK-(26-33)] and examined their actions on dispersed acini prepared from guinea pig pancreas. None of the N terminal fragments or analogues altered basal amylase release. Analogues of CCK (26-32), CCK-(26-31), and CCK-(26-30) inhibited CCK-(26-33)-stimulated amylase, and there was a close correlation between the ability of an analogue to inhibit stimulated amylase and the analogue's ability to inhibit binding of 125I cholecystokinin. N-acetyl-CCK-(26-29)-amide at concentrations as high as 100 microM did not inhibit CCK-(26-33)-stimulated amylase release or binding of 125I CCK. For those analogues that antagonized CCK-(26-33)-stimulated amylase release the antagonism was of the competitive type and was specific for those secretagogues that interact with the cholecystokinin receptor. Removing the C terminal amide from N-acetyl-CCK-(26-31)-amide caused a 10-fold decrease in the inhibitory potency, whereas removing the C-terminal amide from N-acetyl-CCK-(26 30)-amide did not alter the inhibitory potency of the peptide. Removing the sulfate ester from the tyrosine residue in position 27 of N-acetyl-CCK-(26-31) did not alter the inhibitory potency of the peptide, whereas removing the sulfate ester from the tyrosine residue in position 27 of N-acetyl-(26-30) caused a three to fivefold decrease in the inhibitory potency of the peptide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578258 TI - Biochemical markers for suicidal behavior. PMID- 2578259 TI - Early colonic dysplasia: comparison of differential mucin staining and tritiated thymidine labeling. AB - Controversy has arisen regarding the interpretation and significance of histochemical changes in the mucin produced by the globlet cells in colonic mucosa. The shift from sulfomucin to sialomucin, which is readily identified utilizing high iron diamine-alcian blue staining techniques, has been alternately interpreted as a specific, early dysplastic and premalignant change or a nonspecific generalized response to trauma and inflammation, among others. An attempt to clarify this issue was made by comparing mucin changes identified by high iron diamine-alcian blue staining techniques with increases in DNA synthetic activity identified utilizing autoradiographic analysis of tritiated thymidine uptake. Male Holtzman rats were treated with 15 weekly subcutaneous injections of dimethylhydrazine (30 mg/kg per week) (10 rats) or placebo (10 rats). The colons were prepared and fixed, sequential sections were stained with hematoxylin-eosin or high iron diamine-alcian blue, autoradiography was performed. Analyses of labeling index showed no difference in normal background crypts between the control and treatment groups nor in crypts adjacent to those displaying abnormal mucin staining. Crypts with abnormal mucin production (sialomucin dominant) had significantly higher labeling indexes when compared with those of control animals (p less than 0.005). These findings indicate that the shifts in mucin production identified with high iron diamine-alcian blue staining represent crypts with increased and abnormally distributed mitotic activity that is an early dysplastic response to the carcinogenic stimulus. PMID- 2578261 TI - Segmental effect of lumbar epidural hydromorphone: a case report. PMID- 2578260 TI - Inhibition of epinephrine absorption by dextran. PMID- 2578262 TI - Familial exercise-induced anaphylaxis. AB - An 18-year-old hispanic male, his two brothers, father, two paternal uncles, and paternal grandfather experienced cutaneous and cardiorespiratory symptoms during vigorous exercise beginning at about 10 years of age. The propositus was challenged by running to exhaustion and by immersion in hot water. In neither case were allergic signs or symptoms noted; however, plasma histamine rose from undetectable levels to 1.0 and 3.7 ng/ml, respectively. Furthermore, C2 and C5 were significantly reduced and fell during exercise. PMID- 2578264 TI - Workshop on airway smooth muscle. Summary of a conference held September 25-27 1983. AB - Airway smooth muscle contraction and the extreme sensitivity of the airway smooth muscle responses to various stimuli are accepted as key factors in the pathogenesis of asthma and are recognized to be important in other diseases (e.g., bronchitis and cystic fibrosis). A Workshop on Airway Smooth Muscle sponsored by the National Heart, Lung and Blood Institute (September 25 to 27, 1983) identified various avenues of future research. Smooth muscle anatomists pointed to the paucity of quantitative information on airway smooth muscle structure, especially electron microscopic information and details of the neural arrangement. Investigations of the neural network, similar to those that have led to important discoveries in the gut, are urgently needed. Now that intramural ganglia can be studied electrophysiologically (and in vivo!), new information concerning possible local neural modulation can be examined. A similar lack of information was found in the biochemical study of airway smooth muscle. Among potential causes of abnormalities in asthmatic muscles are alterations in membrane channels and pumps, receptor transduction processes, cGMP-mediated processes, and other metabolic pathways. Inflammation and inflammatory mediators appear to play important roles in disease of airway smooth muscle. Utilization of cell isolation and culture, and immunologic and other cell biologic and biochemical methods will accelerate the study of the various cells in the airways, their interactions, and their roles in disease. Of special potential importance are peptide and lipid mediators produced by various airway cells. Development of synthetic analogues and antagonists, including monoclonal antibodies, will provide more specific tools for dissecting these cell-to-cell interactions. Regardless of the level of study--from examination of the whole organism to molecular mechanisms--the fact is that there is no entirely satisfactory animal "model" of asthma or asthmatic muscle, presumably because we do not fully understand the etiology and pathogenesis of asthma. This makes it all the more important to take appropriate opportunities to obtain tissue from asthmatics for laboratory study. Relatively simple, careful studies of asthmatic smooth muscle may prove important, unique insights into its possible abnormalities. PMID- 2578263 TI - Studies of nasal surface basophilic cells. AB - Nasal surface basophilic cells (NSBC), located in both the mucosal and epithelial layer of the human nasal mucous membrane, were studied to elucidate whether or not they are one kind of mucosal mast cells (MMC). Nasal scrapings were collected and used as specimen of NSBC. The results demonstrate that NSBC had functional properties common to MMC in their response to antigen, formalin and compound 48/80. PMID- 2578265 TI - Substance P stimulation of chloride secretion by canine tracheal mucosa. AB - We investigated the effect of a neuropeptide, substance P, on the electrical and ion transport properties of dog trachea. Posterior mucosal tissues were mounted in Ussing chambers and bathed with Krebs-Henseleit solution, pH 7.4, at 37 degrees C. The solution was gassed with 95% O2, 5% CO2. Substance P (10(-7)M) added to the mucosal bath elicited within seconds a rapid rise in short circuit current with a peak response of 23 microA.cm-2 and an increase in tissue conductance of 0.63 mS.cm-2 (p less than 0.001, n = 20). In 6 experiments, 36Cl and 22Na fluxes were measured under short circuit conditions and they revealed that net Cl secretion increased from 1.46 +/- 0.41 to 2.30 +/- 0.74 mueq.cm-2 X h 1 (mean +/- SE, p less than 0.05). This increase was brought about by enhancement of unidirectional submucosa to lumen flux. Net Na absorption of 0.63 +/- 0.09 did not change significantly (0.49 +/- 0.16). Short circuit current response to substance P was not modified by prior tissue incubation with atropine, phenoxybenzamine, propranolol, or naloxone. Removal of mucosal bath calcium and the presence of calcium channel blocker verapamil did not abolish tissue response to substance P. These findings suggest that nerve fibers containing substance P may play a role in regulation of ion transport across the trachea. This action does not appear to be related to the cholinergic, adrenergic, or oplate receptors. PMID- 2578266 TI - Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies. AB - Forty-four patients, including 26 adults and 18 children under 15 years of age, were referred for evaluation of recurrent or persistent illnesses, with symptoms including pharyngitis, lymphadenopathy, fever, headaches, arthralgia, fatigue, depression, dyslogia, and myalgia. Thirty-nine patients were positive for Epstein Barr virus antibody with antibody levels compatible with active infection for at least 1 year. Antiviral capsid antigen and anti-early antigen titers of patients were significantly greater (p less than 0.001) than age-group-matched controls. The frequency, number, duration, and patterns of symptoms, as well as patient sex, were compared by age in study patients seropositive and seronegative for Epstein-Barr virus. Illness patterns were not associated with changes in specific antibody titers or clinical findings. Lymphocyte phenotype and function analyses were done in 11 of the 39 patients positive for Epstein-Barr virus antibody; no consistent differences from normal were found. Only 1 of 32 patients had circulating interferon, in contrast to 7 of 7 patients with acute infectious mononucleosis. There were many adverse consequences of the illness. Epstein-Barr virus infection may not be self-limiting, and the virus may be associated with clinically recognizable illness other than infectious mononucleosis in children as well as in adults. PMID- 2578267 TI - Disseminated infection caused by Cunninghamella bertholletiae in a patient with beta-thalassemia. Case report and review of the literature. AB - Rare cases of acute mucormycosis in immunocompromised persons have been attributed to Cunninghamella bertholletiae. We report the first known case of this organism causing a chronic, indolent, systemic disease clinically similar to entomophthoramycosis. Cunninghamella bertholletiae is an opportunistic pathogen whose morbidity may be underappreciated because it is usually considered to be a laboratory contaminant. PMID- 2578268 TI - Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection. AB - Clinical, serologic, virologic, and immunologic evaluations for 31 adults with chronic illness and fatigue suggested that 23 had persisting Epstein-Barr virus infection. Among these 23 patients, cellular immune mechanisms were generally normal, but 4 had mild immunoglobulin deficiencies. However, 20 patients had abnormal serologic profiles specific for Epstein-Barr virus shown by significantly elevated titers of antibodies to the viral capsid antigen or early antigen, or by a deficiency of late-appearing antibodies. In 11 of 15 patients tested, circulating immune complexes were found. Circulating interferon was not found in 18 patients tested, but the activity of 2-5 oligoadenylate synthetase, an interferon-induced enzyme, was increased in 5 patients studied. Of 19 patients, 18 had persisting suppressor T-cell activity typically found in patients recovering from acute infectious mononucleosis. We believe that the Epstein-Barr virus may be associated with chronic illness in adults. PMID- 2578269 TI - Percutaneous cervical cordotomy: results and complications in a recent series of 100 patients. AB - One hundred and twenty-two percutaneous cervical cordotomies were performed in 100 patients. Of these, 95 suffered from pain associated with malignant disease. Complete pain relief was achieved in 64% of patients, partial relief in 23% and no relief in 13%. Mortality was 6% and exclusively related to postoperative respiratory dysfunction. The results and complications observed in this recent series are discussed in relation to our previous and other authors' experience. For selected patients with cancer pain, percutaneous cordotomy is the most effective operative method available at the present time. PMID- 2578271 TI - An intact hydrophobic N-terminal sequence is critical for binding of rat brain hexokinase to mitochondria. AB - The N-terminal sequence of rat brain hexokinase (ATP: D-hexose-6 phosphotransferase, EC 2.7.1.1) has been determined to be X-NH-Met-Ile-(Ala, Gln) Ala-Leu-Leu-Ala-Tyr-, where X is a blocking group on the N-terminal methionine, probably an N-acetyl group. Modification of this hydrophobic N-terminal segment by endogenous proteases in crude brain extracts resulted in loss of the ability to bind to mitochondria, but had no effect on catalytic activity, resulting in the appearance of nonbindable enzyme reported by several previous investigators to be present in purified hexokinase preparations. Similar results can be obtained by deliberate limited digestion with chymotrypsin (cleavage points marked by arrows in sequence above). Both bindable and nonbindable enzyme, the latter generated either by endogenous proteases or with chymotrypsin, have an identical C-terminal dipeptide sequence, Ile-Ala. The great susceptibility of the N-terminus to proteolysis plus the marked effect that its proteolytic modification has on binding of hexokinase to anion exchange or hydrophobic (phenyl-Sepharose) matrices suggest that this N-terminal segment is prominently displayed at the enzyme surface. Epitopes recognized by two monoclonal antibodies which block binding of hexokinase to mitochondria (but have no effect on catalytic activity) have been mapped to a 10K fragment cleaved from the N terminus by limited tryptic digestion. Thus the binding of hexokinase to mitochondria appears to occur via a "binding domain" constituting the N-terminal region of the molecule, with maintenance of an intact hydrophobic sequence at the extreme N-terminus being critical to this interaction. A resulting specific orientation of the molecule on the mitochondrial surface is considered to be a prerequisite for the observed coupling of hexokinase activity and mitochondrial oxidative phosphorylation. PMID- 2578270 TI - One-carbon metabolism in lectin-activated human lymphocytes. AB - Serine is an essential amino acid for the lectin-mediated transformation of human peripheral blood lymphocytes due to the inability of this cell to synthesize sufficient quantities via either the phosphorylated pathway or by reversal of the serine hydroxymethyltransferase reaction to meet the metabolic demands. The level of intracellular serine is tightly regulated, and the culture medium concentration for optimum cellular transformation falls within a relatively narrow range. The three-carbon atom of serine is the major source of one-carbon units required for purine and pyrimidine nucleotide biosynthesis, but the key effect of both serine deprivation and of high medium serine levels would appear to be on protein synthesis. Although an alternative source of one-carbon units, as provided by high levels of formate in the culture medium, can partially reverse the effects of serine deprivation, the only other demonstrable source of one-carbon units, tryptophan, requires serine for its incorporation and subsequent metabolism. Methionine is also essential for lymphocyte transformation and is involved in the synthesis of a small amount of phosphatidylcholine, although most of this phospholipid is provided by choline and lysophosphatidylcholine from the serum-supplemented culture medium. PMID- 2578273 TI - [Preparation and observation of chromosomes staining]. PMID- 2578272 TI - Lignoceroyl-CoA ligase activity in rat brain microsomal fraction: topographical localization and effect of detergents and alpha-cyclodextrin. AB - Lignoceroyl-CoA ligase activity has been detected in microsomal fractions prepared from rat brain. The synthesis of lignoceroyl-CoA from [1-14C]lignoceric acid and CoASH by this enzyme had an absolute dependence on ATP and Mg2+; ATP could not be replaced by GTP [I. Singh, M. S. Kang, and L. Phillips (1982) Fed. Proc. 41, 1192]. The product has been characterized as lignoceroyl-CoA by the following criteria: Rf on thin-layer chromatography; incorporation of [1 14C]lignoceric acid and [3H]CoASH into the product; acid hydrolysis and identification of the radiolabel in lignoceric acid; and methanolysis and identification of the radiolabel in methyl lignocerate by thin-layer chromatography. The optimal concentrations for CoASH, ATP, and Mg2+ were about 100 microM, 10 mM, and 5 mM, respectively. Lignoceric acid, solubilized by alpha cyclodextrin, Triton X-100, and deoxycholate, was utilized by the lignoceroyl-CoA ligase, but lignoceric acid solubilized by Triton WR-1339 was not. Topographical localization of lignoceroyl-CoA ligase in the plane of rat brain microsomal membranes was determined by the use of Triton X-100, trypsin, and mercury Dextran, and was compared with the marker enzymes, ethanol acyltransferase and thiamine pyrophosphatase, which are known to be localized on the luminal (inner) surface of the microsomal vesicles. Mercury-Dextran (100 microM) and trypsin (trypsin:microsomes, 1:56 w/w) treatment of the microsomes inhibited the lignoceroyl-CoA ligase activity by 70 and 90% without disrupting the microsomal vesicles. Disruption of the vesicles with Triton X-100 increased the activity of both ethanol acyltransferase and thiamine pyrophosphatase by 400% but there was no increase in lignoceroyl-CoA ligase activity. These results suggest that lignoceroyl-CoA ligase is localized on the cytoplasmic surface of the microsomal vesicles. PMID- 2578274 TI - [Current status in the treatment of inoperable non-small cell lung cancer (NSCLC)]. AB - Advances in the treatment of inoperable non-small cell lung cancer (NSCLC) have been falling behind the recent results obtained for small cell lung cancer (SCLC) which had been considered the more malignant type with the shortest survival time. Recently, however, with the introduction of cisplatin, the results of combination chemotherapy for NSCLC have shown a degree of advancement so that an average response rate of 40% and a median survival time (MST) of 8-10 months can be obtained. Our method of combination chemotherapy, PPM (cisplatin, peplomycin, mitomycin C), resulted in an overall response rate of 44% (40% squamous, 29% adeno, 64% large) and an MST of more than 23.3 months in responders. With PFM (cisplatin, 5FU, mitomycin C), response rate was 35% and an MST of 18.7 months was obtained for adenocarcinoma responders. It can therefore be said that we have achieved a new degree of success in the treatment in NSCLC. PMID- 2578275 TI - [Experimental studies on combination chemotherapy of cisplatin with peplomycin against human squamous cell carcinomas in nude mice]. AB - Combination chemotherapy of cisplatin (CDDP) with bleomycin (BLM) or peplomycin (PEP) has exhibited clinical efficacy against squamous cell carcinomas. The combination of CDDP with PEP was studied using five human squamous cell carcinomas in nude mice. When CDDP was administered before PEP treatment, the combination effect was more pronounced than when CDDP was administered after PEP treatment. Especially, when CDDP was administered 5 or 3 days before PEP treatment, marked delay in growth was shown in 4 out of the 5 human carcinomas. From these results, it is thought that human heterotransplanted tumors in nude mice may provide important information in studies of combination chemotherapy. PMID- 2578278 TI - Hydroxyethyl starch in CABG. PMID- 2578276 TI - Biochemical identification of patients with gallstones associated with acute pancreatitis on the day of admission to hospital. AB - Current trends in the treatment of gallstone pancreatitis require rapid diagnosis of cholelithiasis. This study evaluates the diagnostic potential of plasma aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin on the day of admission to hospital in 215 attacks of acute pancreatitis. The optimal diagnostic cut-off level for AST was 60 IU/1. A transient elevation above 60 IU/1 was recorded in 111 (84.1%) of 132 attacks associated with gallstones, but in only 12 (14.5%) of 83 attacks without stones, and was unrelated to the severity of the attack. Elevated levels of alkaline phosphatase and bilirubin were also more common in attacks associated with gallstones but were less reliable for the identification of cholelithiasis than AST. As a sensitive indicator of hepatocyte disruption, the early and transient rise in plasma AST is consistent with the concept of transient ampullary obstruction in gallstone pancreatitis, and may be useful in identifying patients who require urgent surgical or endoscopic disimpaction. PMID- 2578279 TI - Retro-endocytosis of low density lipoprotein by cultured human skin fibroblasts. AB - A fraction of the low-density lipoprotein (LDL) internalized by cells via receptor-mediated endocytosis follows a short-circuit pathway, termed "retro endocytosis," that results in the rapid exocytosis of ligand. Results from the current study suggest that retro-endocytosis of LDL in human fibroblasts is caused by resurfacing of endocytotic vesicles that contain both free and receptor bound ligand, resulting in discharge of vesicular contents and in spontaneous dissociation of LDL from its receptor. The bulk of the released LDL particles had the same size, density, and immunogenic properties as native LDL, indicating that they were discharged intact. Some of the retro-endocytosed LDL was larger than native LDL, and some exhibited altered sedimentation properties. When fusion of endosomes with lysosomes was inhibited by chilling cells to 18 degrees C, the proportion of intracellular LDL subsequently released was unaffected, suggesting that retro-endocytosis does not require lysosomal participation. Furthermore, the shorter the internalization phase the greater was the proportion of LDL subsequently released, suggesting that LDL was discharged from compartments formed early in endocytosis. Retro-endocytosis of LDL was stimulated by agents that neutralize acid intracellular compartments, such as ionophores (monensin) and weak bases (chloroquine and methylamine). Monensin increased the proportion of intracellular LDL released, suggesting that it had a direct effect on retro endocytosis. The effect of weak bases appeared to be secondary to their ability to promote cellular accumulation of undegraded LDL. Thus, retro-endocytosis of LDL becomes a major pathway when intracellular compartments fail to maintain a low pH or where the intracellular concentration of LDL reaches abnormal levels. PMID- 2578277 TI - The pentagastrin test in the diagnosis of the carcinoid syndrome. Blockade of gastrointestinal symptoms by ketanserin. AB - The levels of 5-hydroxytryptamine (serotonin, 5-HT) and substance P (SP) were assayed (using high performance liquid chromatography-electron capture and radioimmunoassay methods) in the peripheral blood of 17 patients with known mid gut carcinoids, 16 of whom had hepatic metastases. All patients had supranormal basal levels of 5-HT and SP. The clinical and hormonal changes induced by two provocation tests, intravenous pentagastrin (PG) and calcium infusion, were compared. Pentagastrin caused flushing in all the patients, induced gastrointestinal symptoms in all but one of the patients with hepatic involvement, and universally elevated circulating 5-HT levels. Pretreatment with a 5-HT2-receptor blocking agent, ketanserin, abolished the gastrointestinal effects but had virtually no influence on either 5-HT levels or flushing induced by intravenous pentagastrin. In contrast, calcium infusion induced carcinoid symptoms in only two of six patients, and this was consistently associated with stimulation of circulating serotonin levels. The authors conclude that 1) 5-HT may be responsible for the gastrointestinal symptoms in carcinoid patients, but it does not seem to play any role in flushing; 2) ketanserin may be a useful therapeutic agent in alleviating gastrointestinal symptoms in carcinoid patients; 3) differential responses to PG suggests that SP is released from a site different from that of 5-HT; 4) it is possible that SP may contribute to the mediation of flushing, but it cannot be the sole agent causing this symptom; and 5) the pentagastrin test with measurements of 5-HT levels in peripheral blood seems to be superior to calcium infusion as a provocative test in documenting the diagnosis of carcinoid disease. PMID- 2578281 TI - Production of a monoclonal antibody-mitomycin C conjugate, utilizing dextran T 40, and its biological activity. PMID- 2578280 TI - Arachidonic acid metabolism in cultured aortic endothelial cells. Effect of cAMP and 3-isobutyl-1-methylxanthine. AB - To investigate the hypothesis that cyclic AMP (cAMP) regulates arachidonic acid metabolism in vascular tissue, we have studied the effects of forskolin (FSK), an activator of adenylate cyclase, and 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, on hormone-stimulated prostacyclin (PGI2) synthesis in porcine aortic endothelial cells grown in culture. In these experiments, bradykinin (1 microgram/ml) and A23187 (0.2 microM) potently stimulated PGI2 biosynthesis (9- and 10-fold respectively). However, prostaglandin synthesis in response to either of these agents was not affected by FSK even though FSK elevated intracellular levels of cAMP 10-fold. IBMX failed to elevate basal cAMP levels when incubated with unstimulated cells. Stimulation of IBMX-treated (0.1 but not 1.0 or 4.0 mM) cells with bradykinin, however, did result in increased cAMP levels, presumably due to PGI2 formation and subsequent activation of adenylate cyclase. In addition to phosphodiesterase inhibition, IBMX inhibited PGI2 formation (72% at 1 mM) in a dose-dependent manner so that, at higher doses of IBMX, cAMP levels returned to baseline. Thus, prostacyclin synthesis inhibition by IBMX could not be attributed to elevated cAMP. In other experiments, IBMX (1 mM) was found to directly inhibit arachidonic acid release (32%) and arachidonic acid metabolism (65%) in endothelial cells and to inhibit arachidonic acid conversion to PGE2 by sheep seminal vesicle microsomes (65%). These data suggest that IBMX directly inhibits both phospholipase and cyclooxygenase activities. These experiments do not support the contention that cAMP regulates these enzymes in cultured aortic endothelial cells. PMID- 2578282 TI - Surface antigen specificity of cold-reactive IgM antilymphocyte antibodies in systemic lupus erythematosus. AB - Monoclonal antibodies to known surface antigens on B cells and on resting and activated T cells of various types were used in several approaches to examine the specificity of IgM antilymphocyte antibodies in systemic lupus erythematosus (SLE). Surface determinants that were sought included: T3, T11, Leu-1, Leu-8 (pan T); T4, T8 (T subset); beta 2-microglobulin (beta 2m); L243, Leu-10 (DR and DS/DC framework, respectively); anti-Tac (interleukin-2 receptor); 5E9 (transferrin receptor); and 4F2, AA1 (other activation antigens). The first strategy was based on inhibition of rosette formation between mouse monoclonal antibody-coated targets and anti-mouse IgG-coated erythrocytes by SLE sera, either directly at 4 degrees C or after modulation of IgM antilymphocyte antibody-reactive target cell antigen at 37 degrees C. Significant rosette inhibition, defined as greater than 2 standard deviations from the mean value for 10 control sera, was seen only for beta 2m (13 of 20 SLE sera were positive; inhibition = 15-58%). Next, relative fluorescence intensity of lymphocyte staining by monoclonal antibodies was assessed by flow microfluorometry after preincubation of cells with SLE serum at 4 degrees C or after modulation of SLE antibody-reactive antigen. Modulation markedly reduced or eliminated SLE antilymphocyte antibody IgM staining. Except for beta 2m, neither cold nor warm temperature preincubations altered the relative fluorescence intensity for the known surface antigens. These data confirm anti-beta 2m as a common antibody specificity in SLE and suggest that antilymphocyte antibodies in this disorder are not directed to Ia or to certain other defined lymphocyte antigens of functional interest. PMID- 2578283 TI - Heterogeneity of colorectal adenocarcinomas evaluated by flow cytometry and histopathology. AB - Flow cytometry and histopathology were utilised in evaluating 50 primary and 16 metastatic colorectal carcinomas to determine the influence of heterogeneity and proportion of dying cells on pathological assessments. A new procedure was developed for staining unfixed whole cells with acridine orange and ethidium bromide to quantify DNA and RNA content and number of dead and dying cells. Attempts were made to reduce interobserver variation in histological assessment and to determine whether flow cytometry could refine current grading and staging procedures. Interobserver variation in grading was not improved by estimating proportions of differing grades in multiple samples from individual tumours. Considerable heterogeneity was observed within tumours although this was less apparent when defining ploidy status than histological grade. No consistent differences were observed between superficial and deep parts of tumours or between primary and secondary tumours by either method of analysis. The proportion of dead and dying cells varied widely between tumours but there was no correlation with tumour grade or stage. Non-diploid tumours were not of more advanced stage or poorer histological grade than diploid tumours. Since ploidy status may be an important prognostic factor, analysis of colorectal carcinomas by flow cytometry could be of greater value than conventional grading and staging procedures. PMID- 2578285 TI - The prognostic value of the monoclonal antibodies HMFG1 and HMFG2 in breast cancer. AB - The monoclonal antibodies HMFG1 and HMFG2 identify antigens of the milk fat globule membrane which are also found on breast epithelial cells. Immunohistochemical staining was performed using both antibodies on formalin fixed, paraffin embedded sections of 93 breast carcinoma, 36 histologically benign lesions and 29 histologically normal breast tissue blocks. In both normal and benign breast disease the staining was largely extracellular whilst in malignant tissue the staining was variable and often intracellular. Nine carcinomas did not stain with either antibody. The staining patterns of malignant tissues were graded and no correlation was found between the grades and survival or indices of prognosis, (the oestrogen receptor status, Bloom's grade and the presence or absence of metastases to the axillary nodes.) This study indicates that with the present methods available for grading staining patterns, although of diagnostic value, these monoclonal antibodies are unlikely to assist in determining either the degree of tumour differentiation or prognosis in breast carcinoma. PMID- 2578284 TI - Heterogeneous expression of cell-surface antigens in normal epithelia and their tumours, revealed by monoclonal antibodies. AB - Most monoclonal antibodies that have been raised to human epithelial tumours bind to only some of the cells in a tumour, showing that tumour cells are very heterogeneous in their expression of antigens. Normal epithelia show the same heterogeneity of antigen expression, as also do cell lines and clones of epithelial cells in culture. It is not related to the mitotic cell cycle. Many, probably most of the antigenic determinants to which the antibodies bind are carbohydrate structures. It is not clear whether variations in antigen expression reflect variations in the differentiated state of the cells or merely variations in the carbohydrate structures on otherwise identical cells, nor is ir clear whether antibodies could be made that bind to all tumour cells by avoiding antibodies to carbohydrate structures. The normal and apparently reversible nature of this heterogeneity of antigen expression conflicts with conventional views that heterogeneity among cells of a tumour is due to permanent genetic change. The heterogeneity within normal clones suggests that cloning is not an adequate way to study heterogeneity in tumour cells. The implications of heterogeneous expression of antigens within tumours for therapeutic and diagnostic application of antibodies are discussed. PMID- 2578286 TI - Placental protein and hormone measurements in twin pregnancy. AB - Maternal serum levels of human placental lactogen (hPL), schwangerschaftsprotein 1 (SP1), pregnancy-associated plasma protein A (PAPP-A), placental protein 5 (PP5) and total oestriol (E3) were measured serially in 35 twin pregnancies during the third trimester. Eighteen pregnancies had major complications including dysmaturity of one or both fetuses in nine, premature labour in six, and placental abruption in three. Serum levels of all five variables were higher than in singletons, this distinction being greatest for hPL and lowest for SP1 and E3. The levels of hPL, PP5 and E3 just before delivery were significantly correlated with the total birthweight, a correlation with placental weight being evident only for hPL and PP5. A significant correlation between the five biochemical variables at 33-34 weeks was only seen between hPL and PAPP-A. Protein and hormone levels in the abnormal twin pregnancies were not apparently different from those in the normal twin pregnancies. These data suggest that only hPL levels biochemically reflect this extreme of fetal and placental growth, but that neither the levels of hPL nor any of the other biochemical indices examined are altered in abnormalities in twin pregnancy. PMID- 2578287 TI - Does ultrasound examination render biochemical tests obsolete in the prediction of early pregnancy failure? AB - Serum levels of fetal, placental and maternal hormones and proteins [alpha fetoprotein (AFP), human chorionic gonadotrophin, human placental lactogen, schwangerschaftsprotein 1, pregnancy associated plasma protein-A (PAPP-A), oestradiol-17 beta, progesterone, pregnancy zone protein] were measured in 108 women with bleeding during the first half of pregnancy. Ultrasound examination at the time of each blood sampling revealed a fetal heart action on at least one occasion in 77 women. Spontaneous abortion occurred in 42 pregnancies, 31 of these showed no ultrasound sign of fetal life, whilst the fetal heart action was observed repeatedly until abortion in the remaining 11 women. Abnormally low levels of PAPP-A were most likely to indicate pregnancy failure, in particular if the fetal heart action was seen at the time of blood sampling. The predictive value, sensitivity and relative risk of a single depressed PAPP-A level were respectively 49, 89 and 41%, the predictive value of a normal result being 99%. With the exception of AFP, all other biochemical indices examined were consistently in the normal range in this group of women. If ultrasound findings were not considered, the biochemical indices were of comparable value in the prediction of spontaneous abortion. PAPP-A levels were uniformly depressed in all patients who spontaneously aborted, frequently weeks before this event, in the presence of a live fetus. PMID- 2578289 TI - Stimulation by calcium and carbamoylcholine of the ouabain-sensitive uptake of 86Rb+ in isolated rat pancreatic acinar cells. AB - The uptake of 86Rb+ was assayed in isolated rat pancreatic acinar cells to determine the effect of calcium and carbamoylcholine on the ouabain-sensitive and ouabain-insensitive components. The presence of calcium in the medium bathing the cells during the preincubation and the main incubation periods was needed to preserve in optimum conditions the uptake of 86Rb+, the stimulation by carbamoylcholine and the sensitivity to ouabain. In the presence of calcium, the ouabain-sensitive component of 86Rb+ uptake was higher than the ouabain insensitive. The ouabain-sensitive component was 3-times lower in cells incubated in a medium lacking calcium and containing 1 mM EGTA, as compared to cells incubated in the presence of calcium. Carbamoylcholine, at 5 X 10(-4) M, stimulated the uptake of 86Rb+ and this effect depended on the presence of calcium in the bathing medium. Maximal stimulation by carbamoylcholine was reached at 0.2 mM calcium. The nett stimulation by carbamoylcholine was inhibited up to 85% by 1 mM ouabain. As judged by digitonin-disruption of plasma membrane, the above-indicated effects were limited to a cytoplasmic pool of 86Rb+ and a leaky plasma membrane could be ruled out. The results suggest that in rat pancreatic acinar cells, carbamoylcholine stimulated the ouabain-sensitive uptake of 86Rb+ and required the presence of calcium in the bathing medium. PMID- 2578288 TI - Effects of Mg2+ on calcium accumulation by two fractions of sarcoplasmic reticulum from rabbit skeletal muscle. AB - Calcium accumulation by two fractions of sarcoplasmic reticulum presumably derived from longitudinal tubules (light vesicles) and terminal cisternae (heavy vesicles) was examined radiochemically in the presence of various free Mg2+ concentrations. Both fractions of sarcoplasmic reticulum exhibited a Mg2+ dependent increase in phosphate-supported calcium uptake velocity, though half maximal velocity in heavy vesicles occurred at a much higher free Mg2+ concentration than that in light vesicles (i.e., approx. 0.90 mM vs. approx. 0.02 mM Mg2+). Calcium uptake velocity in light vesicles correlated with Ca2+ dependent ATPase activity, suggesting that Mg2+ stimulated the calcium pump. Calcium uptake velocity in heavy vesicles did not correlate with Ca2+-dependent ATPase activity, although a Mg2+-dependent increase in calcium influx was observed. Thus, Mg2+ may increase the coupling of ATP hydrolysis to calcium transport in heavy vesicles. Analyses of calcium sequestration (in the absence of phosphate) showed a similar trend in that elevation of Mg2+ from 0.07 to 5 mM stimulated calcium sequestration in heavy vesicles much more than in light vesicles. This difference between the two fractions of sarcoplasmic reticulum was not explained by phosphoenzyme (EP) level or distribution. Analyses of calcium uptake, Ca2+-dependent ATPase activity, and unidirectional calcium flux in the presence of approx. 0.4 mM Mg2+ suggested that ruthenium red (0.5 microM) can also increase the coupling of ATP hydrolysis to calcium transport in heavy vesicles, with no effect in light vesicles. These functional differences between light and heavy vesicles suggest that calcium transport in terminal cisternae is regulated differently from that in longitudinal tubules. PMID- 2578290 TI - Antigenic variation of trypanosomes. PMID- 2578291 TI - Biochemical and immunological characterization of an H2A variant from the mouse testis. AB - A histone H2A variant, protein 'A', has been isolated and purified from the mouse testis. Amino acid composition analysis and electrophoretic properties indicate it to be apparently similar to H2A X X variant present in the mouse L1210 cells. Specific antibodies against protein 'A' have been generated in rabbits and used to study tissue and species distribution in mammals. Protein transfer experiments indicate the presence of antigenically similar proteins in somatic tissues of the mouse. Immunologically similar proteins were also detected in other mammalian testes. The data further indicate that protein A is antigenically distinct from the other members of the H2A family, H2A X 1, H2A X 2 and H2A X Z. PMID- 2578292 TI - Trichotoxin A40. Purification by counter-current distribution and sequencing of isolated fragments. AB - The isolation of the membrane-modifying polypeptide antibiotics from the mycelium of Trichoderma viride 5242 was optimized via extraction with dichloromethane and chromatography on Sephadex LH-20. The components trichotoxin A40 and A50 were separated from each other and purified by multiplicative counter-current distribution. The sequence of proteinase-resistant trichotoxin A40 was determined by combined gas chromatography and mass spectrometry of three isolated N acetylated dodecapeptides and two N-prolylhexapeptides obtained after selective trifluoroacetolysis. Including amino acid exchanges due to natural microheterogeneity, the sequence is Ac-Aib-Gly(LAla)-Aib-LLeu-Aib-LGln-Aib-Aib Aib(LAla )-LAla-Aib-Aib-LPro-LLeu -Aib-DIva(Aib)-LGlu-LValol. In contrast to the eicosapeptide alamethicin, trichotoxin A40 contains only 18 residues, with a higher proportion of alpha-aminoisobutyric acid (Aib), C-terminal L-valinol (Vol), one D-isovaline (Iva) and no proline at the N-terminal part. PMID- 2578293 TI - Inhibition of pancreatic colipase by antibodies and Fab fragments. Selective effects of two fractions of antibodies on the functional sites of the cofactor. AB - Rabbit antiserum was raised against porcine pancreatic colipase and Fab fragments were prepared by papain digestion of purified antibodies followed by purification on protein A-Sepharose. Fab fragments showed inactivation toward porcine colipase activity similar to that of antiserum and purified antibodies. From inactivation studies carried out by incubating porcine colipase and lipase with Fab fragments in the absence of lipid or in the presence of triolein and sodium deoxycholate, it could be concluded that polyclonal antiporcine colipase antibodies contain fractions that bind specifically to epitopes at or near the functional regions of the porcine cofactor. Studies with an enzyme-linked immunosorbent assay showed that cross-reactivity of horse or chicken colipase with antiporcine colipase antiserum was lower than that of the human or porcine protein. Results of immunoactivation kinetic studies performed with the same proteins, fully confirmed these observations. Partial cross-reactivity between porcine and chicken colipases allowed us to fractionate antibodies by immunoaffinity chromatography on immobilized chicken colipase. Fraction I contains antibodies absorbed on porcine colipase not accessible when the cofactor is bound to lipid. Antibodies of fraction II, nonadsorbed on chicken colipase, inactivate porcine colipase preincubated with triolein/deoxycholate. Lipase had a protective effect against inactivation. Antibodies of fraction II bind likely to epitopes close to the specific region of colipase interacting with lipase. Our conclusions are in good agreement with analysis of the sequence of porcine, equine and human colipases by calculating local hydrophilicity indices. PMID- 2578294 TI - Immunoprecipitation of lipid transfer protein activity by an antibody against human plasma lipid transfer protein-I. AB - Two lipid transfer proteins, designated lipid transfer protein-I (Mr 69 000) and lipid transfer protein-II (Mr 55 000), each of which facilitates the transfer of radiolabelled cholesteryl ester, triacylglycerol and phosphatidylcholine between plasma lipoproteins, were purified from human plasma. Immunoglobulin G was prepared from goat antiserum to human lipid transfer protein-I (i.e., anti-human LTP-I IgG). The progressive addition of anti-human LTP-I IgG to buffered solutions containing either a highly purified mixture of human lipid transfer protein-I and lipid transfer protein-II, or highly purified rabbit lipid transfer protein (Abbey, M., Calvert, G.D. and Barter, P.J. (1984) Biochim. Biophys. Acta 793, 471-480) resulted in specific immunoprecipitation and the removal of increasing amounts, up to 100%, of cholesteryl ester, triacylglycerol and phosphatidylcholine transfer activities. However, similar precipitation studies on human and rabbit lipoprotein-free plasma resulted in the progressive removal of all cholesteryl ester and triacylglycerol transfer activities but only 30% (human) or 20% (rabbit) of phosphatidylcholine transfer activity. In all cases more anti-human LTP-I IgG was required to precipitate rabbit lipid transfer activity than human lipid transfer activity. These results suggest that lipid transfer protein-I and lipid transfer protein-II have antigenic sites in common, allowing precipitation of both proteins by specific antibody to lipid transfer protein-I. Most plasma phosphatidylcholine transfer activity is mediated by a protein (or proteins) other than lipid transfer protein-I and lipid transfer protein-II. In lipoprotein-free plasma all cholesteryl ester and triacylglycerol transfer activity, and some phosphatidylcholine transfer activity, is mediated by lipid transfer protein-I (or lipid transfer protein-I and an antigenically similar protein, lipid transfer protein-II. PMID- 2578295 TI - Production and characterization of a monoclonal antibody to dog hepatic lipase. AB - Partially purified dog hepatic lipase was used as antigen to produce monoclonal antibodies in mice. In addition to enzyme-linked immunosorbent assay (ELISA), a reliable and efficient procedure for screening antibodies reacting to hepatic lipase has been developed. A method to distinguish antibodies directing to active site or non-active site epitopes has also been described. We obtained three positive clones that survived after subcloning and expansion. All three monoclonal antibodies possess gamma one (gamma 1) heavy chains and kappa (kappa) light chains. Specificity of monoclonal antibody LDHL No. 537 to dog hepatic lipase was demonstrated by passing post-heparin plasma through its immunoaffinity column. Only dog hepatic lipase was removed by LDHL No. 537 from post-heparin plasma. The immunoaffinity chromatography also demonstrated the co-existence of three enzyme activities (mono- and triacylglycerol lipase and phospholipase A1) on the dog hepatic lipase molecule. The subunit weight of dog hepatic lipase has been estimated at 57500 +/- 600 (n=3) by using immunoaffinity chromatography and the combination of immunoprecipitation and autoradiography methods. PMID- 2578297 TI - Presence of a Ca2+-dependent K+ channel in brown adipocytes. Possible role in maintenance of alpha 1-adrenergic stimulation. AB - We have previously demonstrated mobilization of Ca2+ in and efflux of Rb+ (K+) from isolated hamster brown adipocytes as a consequence of norepinephrine stimulation. We have now investigated the adrenoceptor subtype specificity of these responses and found them both to be of the alpha 1-subtype. Further, we have found that the Rb+ (K+) efflux was dependent upon a primary Ca2+ mobilization event in response to the alpha 1-adrenergic stimulation, since the Rb+ efflux could also be demonstrated by the addition of the Ca2+ ionophore A23187 to the cells. The norepinephrine- and A23187-stimulated Rb+ effluxes were both inhibited by the Ca2+-dependent K+-channel blocker apamin. Apamin also significantly attenuated Ca2+ mobilization in cells in response to a submaximal concentration of norepinephrine. We conclude that alpha 1-adrenergic stimulation of brown fat cells leads to a mobilization of intracellular Ca2+ which, in itself or via other mechanisms, leads to an increase in cytosolic Ca2+ concentration which, in turn, activates a Ca2+-dependent K+ channel, leading to a K+ release from these cells. A possible role for this channel to sustain and augment the response to alpha 1-adrenergic stimulation is discussed. PMID- 2578296 TI - Kinetic analysis of various heparin fractions and heparin substitutes in the thrombin inhibition reaction. AB - Kinetic characteristics of several heparin preparations and substitute heparins were determined to help understand the bases for activity differences. Several materials were highly active in factor Xa inhibition and the reaction rate at constant factor Xa concentration appeared to be predicted by the extent of intrinsic antithrombin III fluorescence change induced by the polysaccharide. Heparin fractions of different molecular weight and affinity for antithrombin III showed similar kinetic parameters in catalysis of the thrombin-antithrombin III reaction when these parameters were expressed on the basis of antithrombin III binding heparin. The latter was determined by stoichiometric titration of the antithrombin III fluorescence change by the heparin preparation. However, the various heparin fractions showed very different specific activities per mg of total polysaccharide. This indicated that functional heparin molecules had similar kinetic properties regardless of size or antithrombin III-binding affinity and is possible because the Km for antithrombin III is determined by diffusion rather than by binding affinity. Substitute heparins and depolymerized heparin were poor catalysts for thrombin inhibition, due at least partially to their affinity for thrombin. This latter binary interaction inhibits thrombin reaction in the heparin-catalyzed reaction. PMID- 2578298 TI - [Lipid peroxidation and the functioning of the Ca pump of the sarcoplasmic reticulum of skeletal muscle in hypercholesterolemia]. AB - During prolonged hypercholesterolemia (HCh), there was a reduction in the efficacy of Ca-pump function of the sarcoplasmic reticulum (SR) of rabbit skeletal muscles, an increase in cholesterol content, and intensification of lipid peroxidation in SR membranes. Supplementation of the cholesterol-rich diet with alpha-tocopherol effectively prevented dysfunction of the SR Ca-pump and reduced the enhanced LPO level in SR membranes without having any effect on cholesterol content in blood serum and SR membranes. The increase in the LPO level seems likely to be primarily responsible for abnormalities in the SR Ca pump during HCh. PMID- 2578299 TI - Platelet agonist synergism by the acute phase reactant C-reactive protein. AB - C-reactive protein is the prototypic acute phase reactant. A self-complexed form (H-CRP) can induce isolated platelets to undergo aggregation, secretion of dense and alpha-granule constituents, and generation of thromboxane A2, but fails to function in platelet-rich plasma (PRP) as a direct agonist. In contrast, when PRP was activated with an amount of adenosine diphosphate (ADP) that produced only reversible platelet aggregation, the presence of H-CRP resulted in irreversible aggregation and the secretion of adenosine triphosphate (ATP). Following a maximum stimulus with ADP alone, where platelet secretion occurred late during the aggregation response, the presence of H-CRP shifted and increased the secretory burst to a time simultaneous with the onset of aggregation. This hypersecretion required H-CRP to be present prior to platelet stimulation or to be added within 15 to 30 seconds following the addition of ADP. H-CRP also potentiated platelet activation stimulated with epinephrine, thrombin, and collagen. When the synergism generated in PRP by H-CRP in the presence of ADP or epinephrine was compared to the synergism similarly produced by aggregated human IgG, collagen, or thrombin, it more closely resembled that of collagen, as reflected by the kinetics and characteristics of synergism and sensitivity to creatine phosphate/creatine phosphokinase or 5,8,11,14-eicosatetraynoic acid. These data provide a philosophically ideal niche for the acute phase (and C reactive protein) in that a platelet-directed activity associated with this acute phase reactant is not utilized unless platelets are otherwise challenged. PMID- 2578300 TI - Non-seminomatous germ cell testicular tumours: residual masses after chemotherapy. AB - Twenty-three consecutive patients with metastatic non-seminomatous germ cell testicular tumours were treated with a combination of cisplatinum, vinblastine and bleomycin. Nineteen had elevated serum tumour marker levels (alpha fetoprotein and beta-subunit HCG) prior to chemotherapy. In 11 of the 19, residual masses were present on the completion of induction chemotherapy despite normal serum tumour marker levels (residual mass after chemotherapy). The management of these 11 patients was based on a policy of observation rather than routine resection of residual deposits and all are currently alive (32-58 months) with ten free of active disease. Two of the eleven required additional chemotherapy when serial tumour marker levels became elevated during follow-up. Another six have been observed without further intervention and have remained well with stable or diminishing deposits. The remaining three have required resection of residual masses, in each case because of mass enlargement despite persistently negative tumour marker levels. None of the masses showed histological evidence of malignancy. A more selective approach to resection of residual masses after chemotherapy is advocated. PMID- 2578301 TI - Teaching terminal care. PMID- 2578302 TI - Prognostic factors for Stage IV Hodgkin's disease treated with MOPP, with or without bleomycin. AB - Prognostic factors for 53 previously untreated patients with Stage IV Hodgkin's disease were analyzed for their effects upon complete remission rate, survival, and disease-free survival following treatment with mechlorethamine, Oncovin (vincristine), procarbazine, and prednisone (MOPP) or MOPP plus bleomycin (MOPP Bleo). Although 75% of those patients with only one site of extranodal disease achieved complete remission, only 25% of those with more than one site of involvement entered complete remission. Seven of the eight patients with more than one extranodal site were dead of disease at 4 years, compared with a 5-year survival of 75% for those with only one site of involvement. Disease-free survival from complete remission was dependent upon the percentage of planned doses of nitrogen mustard actually administered. Patients who received higher doses of nitrogen mustard had significantly longer freedom from relapse and survival after attaining complete remission than those who received reduced doses. Age, symptoms, pathologic features, and presence or size of mediastinal disease did not affect the couple remission rate, survival, or disease-free survival. Patients with Stage IV disease treated with MOPP alone should receive the highest tolerable dose of nitrogen mustard early in their treatment, since those receiving lower doses have a higher risk of relapse. PMID- 2578303 TI - Significance of human chorionic gonadotropin, alpha-fetoprotein, and pregnancy specific beta-1-glycoprotein in the detection of tumor relapse and partial remission in 126 patients with nonseminomatous testicular germ cell tumors. AB - After surgery and initial treatment, 126 patients with nonseminomatous germ cell tumors of the testis were followed by estimation of serum human chorionic gonadotropin (HCG), alpha-fetoprotein (AFP), and pregnancy-specific beta-1 glycoprotein (SP-1). The median follow-up time was 39 months (range, 12-69 months). An evaluation was made of the sensitivity, specificity, and predictive value of these markers to detect tumor relapse (TR) and partial remission (PR) rates. Five of the 35 (14%) Stage I patients had a TR, and in 4 the TR was recognized early by increasing serum levels of HCG (four times) and AFP (one time). In Stage II and III disease 17 of the 91 (18%) patients had a TR or PR. In 15 of the 17 patients TR and PR were associated with elevated serum levels of HCG (nine times), AFP (seven times), and SP-1 (five times). Rising levels of HCG and/or AFP preceded a clinical confirmation of TR and PR by 4 to 8 weeks. Serum SP-1 did not add useful information. The combined use of serum HCG and AFP gives a sensitive indicator for TR and PR: 19 of 22 (86%) of such patients were recognized. The specificity (98% and 100%, respectively) and the predictive value of positive tests (87% and 100%, respectively) were high for both HCG and AFP. PMID- 2578304 TI - Adamantinoma of the tibia. An ultrastructural and immunohistochemical study. AB - The light microscopic, ultrastructural, and immunohistochemical characteristics of two tibial adamantinomas are presented. The immunohistochemical studies utilized specific antibodies against Factor VIII-related antigen and keratin protein, considered as markers for endothelial and epithelial cells, respectively. These revealed positive staining for keratin in the tumor cells of both cases, whereas Factor VIII was not found in either. Ultrastructurally, both tumors had tonofilaments, desmosomes, gap junctions, microvillous-like projections, and basement membranes. Patient 1 had disease that was histologically of the classic spindle cell type; the disease of Patient 2 was atypical and closely resembled an epithelioid angiosarcoma. Immunohistochemical and ultrastructural findings in each case indicate an epithelial component in tibial adamantinoma. PMID- 2578305 TI - Differential cytokeratin and alpha-fetoprotein expression in morphologically distinct epithelial cells emerging at the early stage of rat hepatocarcinogenesis. AB - The various liver cell populations emerging during the transitory reappearance of alpha-fetoprotein (AFP) in serum of 3'-methyl-4-dimethylaminoazobenzene-ingesting rats were analyzed in situ and in vitro on isolated cell preparations in terms of their cytokeratin and AFP expression using single and double indirect immunofluorescence microscopy. A polyclonal guinea pig antibody raised against cow hoof prekeratin, which recognized a Mr 52,000 cytokeratin, was found to react with bile ductular epithelial cells and oval cells but not with hepatocytes. A monoclonal antibody against a Mr 55,000 cytokeratin reacted not only with bile ductular and oval cells but also with hepatocytes. In contrast, a polyclonal antibody against porcine eye lens vimentin reacted with sinusoidal cells and stroma cells. To assess further the heterogeneity of the emerging cell populations, liver cells were isolated after 4 weeks of treatment and fractionated according to cell size and ploidy level into 4 fractions (I to IV) by velocity sedimentation at 1 X g. A cell-type analysis using AFP and albumin as functional markers revealed the presence of AFP-producing cells in Fraction IV at a mean velocity equivalent to that of newborn diploid rat hepatocytes, whereas most of the albumin-producing cells were distributed in Fractions I to III at velocities similar to those of adult tetraploid rat hepatocytes. A similar analysis based on the differential expression of Mr 52,000 and Mr 55,000 cytokeratins and vimentin in bile ductular and other diploid epithelial cells, hepatocytes, and mesenchymal cells showed that large cells in Fractions I to III were tetraploid hepatocytes, whereas viable cells present in Fraction IV were diploid epithelial cells and mesenchymal cells in proportion of 62 and 38%, respectively. These cell populations could be resolved further by changing the sedimentation time. A subsequent examination of the Mr 55,000 cytokeratin containing diploid epithelial cells in Fraction IV using double immunofluorescence microscopy resolved three cell populations with respect to Mr 52,000 cytokeratin and AFP expression, namely, two cell populations expressing either protein marker and a third one containing both markers. These results suggest a ductular origin of oval cells and a possible relation to immature hepatocytes. PMID- 2578306 TI - Tumor phenotype and susceptibility to progression as an expression of subpopulations of initiated murine cells. AB - Currently, it is conceived that a number of events, or hits, are required for the induction of tumors by chemical agents. The first phase of this sequence, initiation, is considered to result from at least one event in the genetic apparatus. Analyses of this sequence, however, usually give little consideration to the nature of the target cell or to the characteristics of the resultant tumors. Vesselinovitch et al. (Cancer Res., 38: 2003-2010, 1978) have reported that a single, small pulse of carcinogen can induce early and numerous liver tumors when administered neonatally to mice with a genetic predisposition to hepatotumorigenesis. In the current study, the nonpredisposed strain C57BL/6N was also shown to be highly susceptible to diethylnitrosamine during the neonatal period. C57BL/6N demonstrated large numbers of two of the three types of liver tumors seen in livers of genetically predisposed mice, one of which required the additional stimulus of dietary phenobarbital for growth. Tumors of more malignant phenotype were demonstrated only in genetically predisposed mice (C57BL/6N X C3H/HeN F1) that received one dose of carcinogen. These findings suggest that the phenotype of a tumor that results from a pulse of a chemical carcinogen may depend upon the target cell. The initiated cells that result from this hit may vary from those that demonstrate very little progression in cell type and may or may not require exogenous enhancement of growth to those that can progress very rapidly to fully malignant behavior. The latter might arise from a hit in a genetically initiated cell, the result of which is a more rapid progression in tumor type. PMID- 2578307 TI - Malignant transformation of a cloned, nontumorigenic mouse epidermal keratinocyte cell line, MSK-C3H-NU, by 7,12-dimethylbenz(a)anthracene. AB - MSK-C3H-NU, a cloned mouse epidermal keratinocyte cell line, was established from the epidermis of C3H/HeN mammary tumor virus-positive nude mice. Although it has lost its diploid chromosome number, the cell line is nontumorigenic, has been stable during serial subcultivations for over 2 years, and has retained some differentiated biological characteristics of normal keratinocytes. MSK-C3H-NU cells were cultured in growth medium containing 7,12-dimethylbenz(a)anthracene. After 2 months, colonies exhibited marked changes in cell morphology, cell arrangement, and keratinization pattern that appeared. The transformation frequency per 10(5) survivors in 7,12-dimethylbenz(a)anthracene-treated (10, 100, and 500 ng/ml) subgroups was 0, 119, and 1370 for Experiment I and 3.9, 238, and 2500 for Experiment II, respectively. Most of these transformed cells became malignant and formed tumors in nude mice. Histologically, the tumors were well differentiated, keratinizing, squamous cell carcinomas showing papillary growths. In 7,12-dimethylbenz(a)anthracene-treated subgroups, cells from colonies that retained the original morphological characteristics did not form tumors in animals, and in control groups, no cell population showed tumorigenicity. In the MSK-C3H-NU cell system, the morphological alterations seem to be strongly associated with malignant conversion. PMID- 2578309 TI - Disulfide bonding of a human prostate tumor-associated membrane antigen recognized by monoclonal antibody D83.21. AB - Previous reports from our laboratory have described the binding specificity of a monoclonal antibody, D83.21, prepared by fusing P3X63/Ag8 mouse myeloma cells with mouse lymphocytes immunized against the DU145 human prostate adenocarcinoma cell line. The D83.21 monoclonal antibody displayed preferential binding to human prostate and bladder carcinoma cell lines and tissues. This antibody was not reactive with a variety of other normal and malignant human cell lines or tissues. Immunofluorescence analysis indicated that the D83.21 antigen was located on the plasma membrane. Biochemical characterization of the target antigen was performed by subjecting detergent-soluble extracts of [3H]glucosamine labeled cells to D83.21 monoclonal antibody affinity chromatography. The radioactive material that was specifically bound and eluted from the affinity column was analyzed by sodium dodecyl sulfate:polyacrylamide gel electrophoresis and fluorography. In the absence of 2-mercaptoethanol, the antigen displayed two prominent bands with molecular weights of 180 and 110 kilodaltons. In the reduced form, the antigen is composed of an Mr 60,000 heavy chain and an Mr 28,000 light chain. The antigen was further resolved using two-dimensional (intact/reduced) sodium dodecyl sulfate: polyacrylamide gel electrophoresis. These analyses indicated that the Mr 180,000 chain was composed entirely of Mr 60,000 subunits, whereas the Mr 110,000 band consisted only of Mr 28,000 subunits. The antigen recognized by the D83.21 monoclonal antibody is therefore a membrane glycoprotein with a subunit structure cross-linked together through disulfide bonds. PMID- 2578308 TI - Isolation and characterization of a monoclonal antibody specific for epithelial cells. AB - Monoclonal antibodies were generated to antigens on human foreskin keratinocytes to identify epithelial-specific molecules. Spleen cells from BALB/c mice, immunized with membrane preparations from primary explants of foreskin epithelial cells, were fused with the NS-1 mouse myeloma line. Hybridoma supernatants were screened for the desired immunological reactivity using enzyme-linked immunosorbant binding assays. Hybridomas secreting antibodies reacting with epithelial cells, but not fibroblasts or lymphocytes, were cloned by limiting dilution, and two stable clones producing immunoglobulin M K antibodies were selected for study. Evaluation of fixed paraffin-embedded human tissue by an indirect immunoperoxidase technique revealed that the antibodies bound most strongly to normal stratified squamous and transitional epithelium, and squamous and transitional cell carcinomas. Antibodies from the cloned hybridomas also reacted with primary cell cultures of foreskin keratinocytes, pulmonary epithelium, fetal liver, and amnion cells, but not with primary cultures of nonepithelial cells. Further testing by enzyme-linked immunosorbent assays revealed that the antibodies reacted with some long-term cell lines derived from epithelial tumors. Nonepithelial cell lines were not stained by the antibodies. Indirect immunofluorescent studies indicated that staining was confined to the cell surface. These antibodies may prove useful in studies of differentiation markers of human epithelial cells. PMID- 2578310 TI - High-molecular-weight glycoproteins of human teratocarcinoma defined by monoclonal antibodies to carbohydrate determinants. AB - Three mouse monoclonal antibodies to distinct cell surface antigens were derived from immunizations with cells of Tera-1, a human teratocarcinoma cell line, and a membrane preparation of placental tissue. The distribution of the antigens on 165 cultured lines of various human tumors and normal cells was determined by mixed hemadsorption assays and on fresh tissues by immunofluorescence staining. K4 antigen is expressed on cell lines derived from teratocarcinomas but not on any other cultured cell tested. Normal adult colonic epithelium, some fetal tissues, and specimens of testicular teratocarcinoma were also K4 positive. K21 antigen was detected on teratocarcinoma cell lines and, at more than 100-fold lower levels, on cultures of normal and malignant kidney epithelium but not on other cultured cells. K21 expression in normal tissues is restricted to the epithelium of fetal intestine and bronchus. Other fetal tissues and all adult normal tissues tested lacked K21. A subset of teratocarcinoma specimens (5 of 8) was reactive with antibody K21. P12 antigen is represented on a wide range of cell lines and tissues, including a subset of teratocarcinomas. AbK4, AbK21, and AbP12 react with carbohydrate sequences present on high-molecular-weight glycoproteins. AbK21 and AbP12 recognize the lacto-N-tetraose and lacto-N-fucopentaose III (X-hapten) structures, respectively, whereas AbK4 reacts with a neuraminidase-sensitive determinant. PMID- 2578311 TI - Keratin expression in normal esophageal epithelium and squamous cell carcinoma of the esophagus. AB - The 8-nm keratin filament is a major component of the cytoskeleton of epithelial cells and epithelial-derived cancers (carcinomas). Recently, it has been shown that the pattern of keratins produced by an esophageal epithelial cell undergoes change upon malignant transformation. In order to evaluate the potential importance of these differences in providing improved diagnostic techniques for pathology, we have investigated the consistency of the patterns of keratins expressed in normal esophageal epithelium, squamous cell carcinoma (SQCC) of the esophagus, and cultured esophageal epithelial cells. In six patients, the keratin pattern expressed by SQCC of the esophagus and corresponding normal esophageal epithelium was consistently different as judged by immunoblot analysis of electrophoretically separated protein extracts. Whereas the SQCCs typically expressed major keratins with molecular weights of 58,000, 56,000, 50,000, and 46,000, the normal esophageal epithelium produced two major keratins with molecular weights of 58,000 and 52,000 and a minor keratin with a molecular weight of 56,000. When normal esophageal epithelial cells were grown in tissue culture, their keratin pattern changed, and keratins with molecular weights of 58,000, 56,000, 52,000, 50,000, 46,000, and 40,000 were expressed. Although some minor variations in keratin patterns were seen, the major differences in keratin pattern expressed by normal esophageal epithelial tissue, SQCC of the esophagus, and cultured esophageal cells were consistent and reproducible. PMID- 2578312 TI - Transcriptional regulation of c-myc during chemically induced differentiation of HL-60 cultures. AB - Previous studies have demonstrated both an elevated level of cellular myc homologous RNA in HL-60 cultures and a decrease in this messenger RNA following the chemically induced differentiation of HL-60 cells. A nuclear transcription system isolated from HL-60 cells was used to investigate whether an alteration in the rate of transcription of the c-myc gene was associated with this decrease in myc RNA. Five days after the addition of either 180 mM dimethyl sulfoxide or 60 nM 12-O-tetradecanoylphorbol-13-acetate to HL-60 cultures, transcription of the c myc gene was markedly reduced when compared with control cultures. This specific decrease was not accompanied by an alteration in either the bulk rate of transcription of the c-myc copy number. This suggests that the decreased cellular myc RNA levels are due to decreased transcription of the myc protooncogene. PMID- 2578313 TI - Prognostic importance of prostate-specific antigen for monitoring patients with stages B2 to D1 prostate cancer. AB - To evaluate the prognostic value of prostate-specific antigen (PA) for detection of tumor growth after definitive therapy, 602 sera from 70 patients with stages B2 to D1 prostate cancer (26 of whom recurred) were analyzed in a blind study. Using Cox's proportional-hazards model, a highly significant association was found between serially measured PA and disease-free survival time (p = 0.0002). A positive predictive value of 100% was found for some markedly elevated PA levels and confirmed recurrence of disease. In fact, this study suggested that once a PA level of 88 ng/ml was reached, there was an average time of less than 2 months before a recurrence was clinically confirmed. Tumor growth in patients who recurred was indicated by a PA elevation before recurrence in 92% (24 of 26) as opposed to 20% (9 of 44) in disease-free patients. Additionally, in these 24 of 26 patients, levels of PA were elevated 12 months (mean lead time) before a confirmed disease recurrence. In patients who were still disease free, serial PA appeared to increase concurrently with putative tumor growth as shown by the initial surgical stage. Generally, the greater the PA level the more advanced was the stage of disease (B2 to D1). These data suggest that PA may be a useful adjuvant marker for monitoring tumor growth in patients with regionally confined prostate cancer. PMID- 2578314 TI - Chemotherapy for esophageal cancer with mitoguazone, methotrexate, bleomycin, and cisplatin. AB - Eighteen patients with measurable or evaluable lesions from squamous cancer of the esophagus received a regimen combining four active agents on an outpatient basis. Nine of 14 evaluable patients (64%, or 50% of 18 patients entered) responded: four of five with previously untreated regional disease and five of nine with recurrent or metastatic disease. Median duration of response in the latter group was 5 months (longest response, 13). Treatment was well-tolerated in all patients but one, who developed signs of severe methotrexate toxicity and died of sepsis. PMID- 2578315 TI - Electrophoretic and cytological evidence for heterogeneity of pancreatic acinar cell responsiveness to carbachol, caerulein and secretin. AB - Incubation of rat pancreatic lobules for 90 min with optimal concentrations of caerulein, carbachol or secretin caused the release of about 30% of the amylase content. Combination of secretin with carbachol or caerulein increased the amylase output to about 40%. With secretin, as with carbachol or caerulein, heterogeneity of cellular responsiveness was observed, some acini being partially or completely depleted of their zymogen granules, whereas others appeared to be resting. When secretin was combined with carbachol or caerulein, granule depletion, originally confined to small groups of neighbouring acini, spread to form large areas of degranulated cells, sometimes comprising a whole section of a lobule. In dispersed acini, under the same conditions, carbachol caused the release of about 60% of the amylase content, and secretin 40%. When both secretagogues were combined, a significant increase to 78% was observed. Under these conditions, there was some important cellular damage, as indicated by the release of 20% of the amylase content and between 6 and 12% of lactate dehydrogenase into the media, in the absence of stimulus. These results were corroborated by cytological observations. On the basis of their secretory response two groups of acini can be distinguished, those that respond to carbachol, caerulein or secretin and those that respond to the combination of secretin with carbachol or caerulein. Electrophoretic patterns of secretory proteins released by lobules stimulated by these different types of secretagogues were essentially similar. The pattern was quite different, however, in the absence of a stimulus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578316 TI - Origin and distribution of neuropeptide Y-, vasoactive intestinal polypeptide-and substance P-containing nerve fibers in the urinary bladder of the rat. AB - The origin and distribution in the urinary bladder of nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and substance P (SP) were investigated in rats. Experimental procedures comprised preganglionic decentralization or postganglionic denervation of the bladder and also chemical sympathectomy as well as capsaicin treatment of newborn rats. Nerve fibers containing NPY were richly distributed in the detrusor muscle and also in the pelvic ganglia. Numerous NPY-containing nerve cell bodies were found in pelvic ganglia. A rich occurrence of VIP fibers and a more sparse distribution of SP containing fibers were also found in the bladder as well as a relatively rich representation of VIP-containing nerve cell bodies in the pelvic ganglia. After decentralization the intensity of VIP and NPY immunofluorescence increased in nerve cell bodies of the pelvic ganglia and in nerve fibers in the wall of the bladder. Postganglionic denervation, on the other hand, eliminated all peptides examined in the bladder wall. After postganglionic denervation the situation in the ganglia was approximately the same as after decentralization. Chemical sympathectomy (6-OHDA) did not seem to change significantly the frequency and distribution of VIP-, SP- and NPY-fibers in the muscle layer of the bladder or in the pelvic ganglia, while the NPY-containing nerve fibers in the submucosal layer and around blood vessels of the bladder disappeared. Adrenergic nerve fibers in the wall of the bladder (visualized by histofluorescence) were markedly reduced in number after administration of 6-OHDA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578317 TI - Neuropeptide Y-, substance P- and VIP-immunoreactive nerves in cat spleen in relation to autonomic vascular and volume control. AB - Neuropeptide Y (NPY)-immunoreactive (IR) nerve fibres were found around both arteries and veins and in smooth muscle trabeculae of the cat spleen with the highest density on the arterial side. Considerably more tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH)-positive than NPY-IR nerves were seen in the trabeculae and splenic capsule. The NPY-IR nerves in the spleen most likely originated in the coeliac ganglion, since (1) splanchnic nerve sectioning did not change the splenic NPY-IR nerves, (2) most neurones in the coeliac ganglion were NPY-IR, as well as DBH- and TH-positive, and (3) NPY-IR was transported axonally from the coeliac ganglion towards the spleen via the splenic nerve. Local NPY infusion in the isolated, blood-perfused cat spleen caused a marked increase in splenic vascular resistance and a small volume reduction. NA caused a comparatively larger reduction in splenic volume than NPY in addition to vasoconstriction. VIP-IR cell bodies in the coeliac ganglion were NPY- and TH negative. VIP-IR nerves were seen both around the splenic artery and vein as well as around arterioles and within venous trabeculae of the spleen. VIP infusion caused reduction of splenic perfusion pressure (i.e. vasodilation) as well as an increase in splenic volume. Substance P-IR nerves, most likely of splanchnic afferent origin, were present in the coeliac ganglion around the splenic artery and arterioles of the spleen. Infusion of substance P induced marked reduction in perfusion pressure and a reduction in splenic volume. Enkephalin-immunoreactive nerves of splanchnic origin surrounded some TH- and NPY-positive, coeliac ganglion cells. It is concluded that several vasoactive peptides are located in splenic nerves. NPY is present in noradrenergic neurones and causes mainly increased vascular resistance. VIP occurs in non-adrenergic neurones of sympathetic origin and induces vasodilation and relaxation of the capsule. Finally, substance P is present in peripheral branches of spinal afferent nerves and causes vasodilation and capsule contraction. Stimulation of the splenic nerves may thus release several vasoactive substances in addition to noradrenaline, exerting a variety of actions. PMID- 2578318 TI - The flightless Drosophila mutant raised has two distinct genetic lesions affecting accumulation of myofibrillar proteins in flight muscles. AB - We have used a combination of histological, molecular, and genetic techniques to investigate the flightless Drosophila mutant raised. Electron microscopy of indirect flight muscles of raised homozygotes confirms that they are grossly abnormal, lacking thin filaments and Z discs. These defects correspond to aberrant protein accumulation in thoraces, where several myofibrillar components are reduced or absent. Utilizing the germ-line transformation technique we demonstrate that one genetic lesion associated with the raised phenotype resides within the act88F actin gene, which, as a result, fails to specify normal mRNA accumulation during thoracic muscle differentiation. We also provide evidence for a distinct second genetic lesion, which apparently eliminates proper posttranslational modification of two myofibrillar proteins, one of which is actin. PMID- 2578319 TI - Nuclear segregation of U2 snRNA requires binding of specific snRNP proteins. AB - We analyzed the mechanism by which snRNAs are accumulated in the cell nucleus by introducing in vitro mutations into a cloned Xenopus U2 snRNA gene. The mutant genes were then expressed by microinjection into living oocytes. Using autoimmune antisera we localized the binding sites of snRNP proteins on the mutant U2 snRNAs. Sm antigen, a component shared by most U snRNPs, requires for binding a sequence containing AUUUUUG, a feature partly conserved in U1, U2, U4, and U5 snRNAs. A U2-specific protein defined by a second antiserum requires the two 3' loops of the U2 RNA molecule for binding. Mutant U2 transcripts unable to bind Sm antigen do not accumulate in the nucleus. Since Sm antigenic proteins are cytoplasmic and excluded from the oocyte nucleus when not bound to snRNA, we propose that a karyophilic domain may become exposed on formation of the RNA protein complex. PMID- 2578320 TI - Cell surface expression of an in vitro recombinant class II/class I major histocompatibility complex gene product. AB - Chimeric histocompatibility genes encoding the amino-terminal (beta 1) domain of the class II Ak beta polypeptide and the carboxy-terminal (C2, transmembrane, and intracytoplasmic) domains of either the class I H-2Ld or H-2Dd molecules were stably introduced into mouse L cells. Although both were transcribed, only 5' Ak beta/3' H-2Dd transformants had significant cell membrane expression of a 30-40 kd, heterogeneous glycoprotein containing Ak beta 1 and H-2Dd (C2) serological epitopes. These transformants had a unique pattern of reactivity with monoclonal antibodies previously identified as requiring the Ak beta 1 domain for recognition of complete I-A molecules. These results allow new insight into the structural requirements for cell surface expression of proteins and provide unique cellular reagents for the dissection of humoral and cell-mediated recognition of MHC molecules. PMID- 2578321 TI - Developmentally controlled and tissue-specific expression of unrearranged VH gene segments. AB - It is generally accepted that unrearranged immunoglobulin VH gene segments are not expressed and that assembly of a complete heavy chain gene is required to activate a previously silent VH promoter. We report that unrearranged VH gene segments are indeed expressed at a high level, but only in a developmentally controlled and tissue-specific manner. Unrearranged VH expression is limited to the very early stages of the B-lymphocyte differentiation pathway, and it is most prominent in cells undergoing VH to DJH rearrangement. Germ-line VH expression is independent of the heavy chain enhancer, may be controlled by 5' sequence elements, and is repressible by LPS. In contrast to earlier interpretations, our results demonstrate that the lack of unrearranged VH segment expression in mature, Ig-secreting cells is due to the inactivation of a previously active locus. These findings may provide insight into the mechanisms that control ordered rearrangement and allelic exclusion. PMID- 2578322 TI - Sex-specific regulation of yolk protein gene expression in Drosophila. AB - Many of the genes in the regulatory hierarchy controlling sex determination in Drosophila melanogaster are known. Here we examine how this regulatory hierarchy controls the expression of the structural genes encoding the female-specific yolk polypeptides. Temperature shift experiments with a temperature-sensitive allele of the sex determination regulatory gene transformer-2 (tra-2) showed that tra-2+ function is required in the adult for both the sex-specific initiation and maintenance of YP synthesis. Control of the YP genes by this regulatory hierarchy is at the level of transcription, or transcript stability. The results of temperature shift experiments with abdomens isolated from tra-2ts homozygotes support the notion that the tra-2+ function acts in a cell-autonomous manner to control YP synthesis. These results provide a paradigm for the way this regulatory hierarchy controls the terminal differentiation functions for sexually dimorphic development. PMID- 2578323 TI - 5-Azacytidine permits gene activation in a previously noninducible cell type. AB - We previously reported that silent muscle genes in fibroblasts could be activated following fusion with muscle cells to form heterokaryons. This activation did not require changes in chromatin structure involving significant DNA synthesis. We report here that muscle gene activation was never observed when HeLa cells were used as the nonmuscle fusion partner. However, if HeLa cells were treated with 5 azacytidine (5-aza-CR) prior to fusion, muscle gene expression was induced in the heterokaryons. The genes for both an early (5.1H11 cell surface antigen) and a late (MM-creatine kinase) muscle function were activated, but were frequently not coordinately expressed. These results suggest that the expression of two muscle genes, which is usually sequential, is not interdependent. Furthermore, changes induced by 5-aza-CR, presumably in the level of DNA methylation, are required for muscle genes in HeLa cells to be expressed in response to putative trans-acting regulatory factor(s) present in muscle cells. PMID- 2578324 TI - Movement of organelles along filaments dissociated from the axoplasm of the squid giant axon. AB - Cytoplasmic filaments, separated from the axoplasm of the squid giant axon and visualized by video-enhanced differential interference contrast microscopy, support the directed movement of organelles in the presence of ATP. All organelles, regardless of size, move continuously along isolated transport filaments at 2.2 +/- 0.2 micron/sec. In the intact axoplasm, however, movements of the larger organelles are slow and saltatory. These movements may reflect a resistance to movement imposed by the intact axoplasm. The uniform rate of all organelles along isolated transport filaments suggests that a single type of molecular motor powers fast axonal transport. Organelles can attach to and move along more than one filament at a time, suggesting that organelles have multiple binding sites for this motor. PMID- 2578325 TI - Single microtubules from squid axoplasm support bidirectional movement of organelles. AB - Single filaments, dissociated from the extruded axoplasm of the squid giant axon and visualized by video-enhanced differential interference contrast microscopy, transport organelles bidirectionally. Organelles moving in the same or opposite directions along the same filament can pass each other without colliding, indicating that each transport filament has several tracks for organelle movement. In order to characterize transport filaments, organelle movements were first examined by video microscopy, and then the same filaments were examined by electron microscopy after rapid-freezing, freeze-drying, and rotary-shadowing. Transport filaments that supported bidirectional movement of organelles are 22 nm to 27 nm in diameter and have a substructure indicative of a single microtubule. Immunofluorescence showed that virtually all transport filaments contain tubulin. These results show that single microtubules can serve as a substratum for organelle movement, and suggest that an interaction between organelles and microtubules is the basis of fast axonal transport. PMID- 2578326 TI - Establishment of four mouse mastocytoma cell lines. AB - Four mastocytoma cell lines were isolated from four different mouse mastocytoma tumors. The tumors had been induced in mice treated with tetramethylpentadecane (pristane) and infected with Abelson murine leukemia virus. The cell lines have been carried in culture for over a year and can induce tumors when injected into the mouse strain in which the tumor originated. The cells contain histamine, have high affinity IgE receptors and release histamine by IgE, immune complex or ionophore A23187-induced reactions. This histamine release reaction requires Ca2+, is optimal at 37 degrees C, and is blocked by a number of metabolic inhibitors. There is no requirement for phosphatidylserine. Cloned sublines have been obtained which will be useful for Fc epsilon R, Fc gamma R; and histamine release studies. PMID- 2578327 TI - Effect of prostaglandin E2 on the gamma-interferon induction of antigen presenting ability in P388D1 cells and on IL-2 production by T-cell hybridomas. AB - The effect of prostaglandin E2 on the gamma-interferon (IFN-gamma)-mediated induction of Ia expression and antigen-presenting activity in macrophage cell lines was studied. Using a lymphokine preparation obtained from the T-cell hybridoma FS7-20.6.18 (known to produce interferon) to induce the expression of Ia in P388D1 cells, the influence of PGE2 on this phenomenon was studied. Screening of the cell cultures by indirect immunofluorescence using an anti-I-Ad monoclonal antibody confirmed the inhibitory effect of PGE2 in the induction of I Ad. However, the inhibition of the antigen-presenting ability of these cells, as measured by their capacity to stimulate interleukin 2 (IL-2) production by antigen-specific, I-region-restricted (Ag/I) T-cell hybridomas, was more difficult to demonstrate and was only evident when using low concentrations of Ia inducing lymphokines or when using "low avidity" T-cell hybridomas. The latter were distinguished by the limited response (in the form of IL-2 production) that was observed when they were tested with P388D1 cells that had been induced with IFN-gamma. By contrast, PGE2 had profound inhibitory effects on the ability of T cell hybridomas to secrete IL-2 in response to Ag/I or concanavalin A. These results suggest that although PGE2 inhibits the full induction of Ia on macrophages, it has little effect on the induction of Ag/I presentation by the same cells, probably because most T cells require relatively low levels of Ia on the surface of presenting cells. T-cell responses to Ag/I are inhibited, however, because of the effects of PGE2 on the T cells themselves. PMID- 2578328 TI - The roles of two peritoneal T-lymphocyte populations in the in vivo rejection of methylcolanthrene-induced sarcoma. AB - Two phenotypically distinct T-lymphocyte populations infiltrating the peritoneal site of active tumor rejection were found to have specific reactivity against methylcolanthrene (MCA)-induced sarcoma(s) in two separate biological assays. One, expressing a Lyt 1+2- phenotype, mediates specific delayed type hypersensitivity (DTH) reaction to the immunizing MCA tumor transplantation antigen, and the other, expressing a Lyt 1+2+ phenotype, transfers in vivo protection against the MCA tumor in Winn assay. This latter antitumor immunity was specific for individually distinct transplantation antigens of each MCA sarcoma line. In contrast, standard transplantation tests by direct (whole animal) challenge demonstrated considerable tumor cross-reactivity. These findings and the relative contributions of the two T-cell populations are discussed in terms of effector mechanism. PMID- 2578330 TI - The role of the thymus in the maintenance of natural killer cells in vivo. AB - This report describes a model for investigating the role of the thymus in regulating natural killer (NK) cell activity in vivo. Evidence is presented that the thymus can regulate NK cells, and that at least some NK cells can develop without thymic help. Marrow from thymectomized rats depleted of circulating T cells by thoracic duct cannulation was transplanted into rats without a thymus (1 degree ATX.BM). These 1 degree ATX.BM rats had NK cell levels above controls 3 months after reconstitution but markedly depressed NK cell levels by 9 months. When 1 degree ATX.BM marrow was used to reconstitute rats with or without a thymus, those without a thymus (2 degrees ATX.BM) exhibited low NK cell levels after 3 months, and a similar result was obtained when 2 degrees ATX.BM marrow was used to reconstitute 3 degrees ATX.BM rats. The low NK cell levels in 2 degrees and 3 degrees ATX.BM rats were due to a deficiency in spontaneously cytotoxic NK cells, as they had normal numbers of interferon-responsive pre-NK cells. Spleen cells from 2 degrees and 3 degrees ATX.BM rats produced less interferon than control spleen cells when cultured with P815 tumor cells in vitro. However, 2 degrees and 3 degrees ATX.BM rats had higher numbers of large granular lymphocytes than controls despite their low NK cell levels. In marked contrast to 2 degrees and 3 degrees ATX.BM rats, spleen cells from 4 degrees ATX.BM rats had higher levels of cytotoxicity and a higher frequency of both spontaneously cytotoxic and pre-NK cells than controls. The 4 degrees ATX.BM rats also had the highest frequency of large granular lymphocytes in the spleen. PMID- 2578329 TI - Pretreatment of rats with anticollagen IgG renders them resistant to active type II collagen arthritis. AB - Intravenous administration of 24 mg of affinity-purified rat anticollagen IgG induced a polyarthritis in recipient rats within 48 hr. This polyarthritis was transient and hind paw diameters returned to normal values within 12 days. IgG and C3 could be detected on the articular cartilage by immunofluorescence up to 16 days after antibody administration. Administration of 24 mg of rat anticollagen IgG to these antibody-treated rats did not induce a second phase of polyarthritis. In addition, recovered rats that had been pretreated with antibody were resistant to arthritis when Type II collagen was administered intradermally. In these rats, serum anticollagen IgG levels were significantly lower than in control rats which were not treated with antibody. Pretreatment of rats with anticollagen IgG did not have an effect on the severity or the incidence of adjuvant-induced arthritis. In addition, pretreatment of rats with anticollagen IgG did not have an effect on the development of a humoral response to ovalbumin. PMID- 2578331 TI - In vitro growth and maintenance of two morphologically distinct populations of thymic epithelial cells. AB - Cultures of thymic epithelial cells were generated and maintained in valine-free minimum essential medium (MEM) supplemented with 690 mg/liter of D-valine. These cultures have been maintained for 1 year through multiple passages by trypsinization of 60-70% confluent monolayers. Large and small epithelial cells were present in early cultures. They were separated into two stable subpopulations based on (1) their differential growth rates and (2) their differential adherence to the culture substratum. These morphologically distinct cell populations, TECS and TECL, were 100% keratin positive and contained cells with desmosomes and tonofilaments, all characteristics of epithelial cells. Esterase analysis of both cell populations revealed a 1 and 9% esterase-positive cell population in cultures of keratin-positive small (TECS) and large (TECL) cells, respectively. The percentages of esterase-positive cells corresponded to the 2 and 10% populations of TECS and TECL, respectively, that contained both desmosomes and phagolysosomes. These results establish conditions for the long term propagation of pure thymic epithelial cells. Such cultures can be used to study the functional interactions between epithelial cells and lymphoid cells. Morphologic and histochemical analyses have identified subsets of these cells which may prove to have differential effects on thymocyte proliferative and developmental processes. PMID- 2578332 TI - The acquisition of encephalitogenicity after sensitized cells are conditioned with myelin basic protein or concanavalin A. AB - When cells from rats immunized against neural antigens are incubated with myelin basic protein or concanavalin A, their ability to transfer experimental allergic encephalomyelitis (EAE) is greatly increased. Using the rapid, localized form of EAE, we have shown that the increased encephalitogenicity of these cells was not manifest, or not fully manifest, in 1 day after passive transfer. Expression of the increased encephalitogenic potency required a period of residence in the recipient animal and this period did not depend on the duration of incubation in vitro. Conditioned cells were fully capable of eliciting the neutrophilic form of EAE, which is consistent with the notion that the recipient's mononuclear cells were not essential for the expression of the encephalitogenic potential of conditioned donor cells. PMID- 2578333 TI - [Will enzyme tests replace biological methods of determining interferon?]. PMID- 2578334 TI - 5-azacytidine potentiates initiation induced by carcinogens in rat liver. AB - To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA. PMID- 2578335 TI - Ryanodine as a tool to determine the contributions of calcium entry and calcium release to the calcium transient and contraction of cardiac Purkinje fibers. AB - Our object was to assess the relative roles of transsarcolemmal calcium entry and intracellular calcium release in the contraction of cardiac Purkinje fibers. We observed intracellular calcium transients, membrane potential, and contraction in aequorin-injected canine cardiac Purkinje fibers exposed to highly selective pharmacological modifiers of excitation-contraction coupling. To influence selectively the release of calcium from the sarcoplasmic reticulum, we used the plant alkaloid, ryanodine. To influence calcium entry, selectively, we used either the calcium channel antagonist, nitrendipine, or the calcium channel agonist, Bay k 8644. Ryanodine alone (1 microM) reduced both components of the intracellular aequorin luminescence signal (L1 and L2). In three muscles, the luminescence signals were 3% of control in amplitude (standard error of the mean, 2%) without two distinct components and the twitch tension was 2% of control (standard error of the mean, 3%), whereas the action potential was prolonged. The aequorin signal and twitch remaining in ryanodine were abolished by the calcium antagonist nitrendipine (10 microM), which also lowered the action potential plateau, consistent with the block of functional calcium channels. In two experiments, the calcium-channel agonist, Bay k 8644, in the presence of ryanodine, increased the aequorin luminescence and the contraction, but only to a very small fraction of their control values. Sodium withdrawal in potassium-free, ryanodine-containing solution produced large slow increases in calcium and tension, showing that tension could still be produced, that aequorin remained functional, and that sodium/calcium exchange was not inhibited by ryanodine. Caffeine increased intracellular calcium, showing that calcium stores were not depleted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578336 TI - A dihydropyridine (Bay k 8644) that enhances calcium currents in guinea pig and calf myocardial cells. A new type of positive inotropic agent. AB - Bay k 8644 is a structural analog of nifedipine with positive inotropic activity. The mechanism of drug action was evaluated by measuring the effects of Bay k 8644 on twitch tension, action potential configuration, and calcium channel currents in myocardial cells. Bay k 8644 increases twitch tension in guinea pig atria without changing the time course of tension development. The drug does not occlude the effect of isoproterenol on twitch tension. The effects of Bay k 8644 on atrial twitch tension are highly dependent on the frequency of stimulation. Maximal inotropic effects are observed at approximately 0.5 Hz, but no inotropic effect occurs at 0.003 Hz (a rested-state contraction). Since positive inotropic effects only occur with frequent electrical stimulation, they are not due to an intracellular action or to mechanisms that elevate cell calcium in quiescent muscle, such as inhibition of the Na,K-ATPase. Bay k 8644 increases the action potential duration of calf ventricular muscle and Purkinje fibers. Effects on action potential duration are occluded by 1 microM nisoldipine, which specifically blocks calcium channels. The interaction of Bay k 8644 with calcium channels in calf Purkinje fibers was studied using the two-microelectrode voltage clamp technique. Strontium was used as a charge carrier to minimize current through calcium-activated channels and to avoid changes in calcium conductance due to changes in intracellular calcium. Bay k 8644 increases strontium currents and alters the time- and voltage-dependence of channel opening. The greatest percent increase in strontium current occurs for weak depolarizations. For strong depolarizations, strontium current is increased most at the beginning of a test pulse. The drug-induced changes in calcium channel gating are inconsistent with a calcium- or cyclic adenosine monophosphate-mediated effect, and indicate a novel mechanism of action on calcium channels. Thus, Bay k 8644 is the first positive inotropic agent shown to act specifically and directly on calcium channels. PMID- 2578338 TI - Modified critical conditions for prestaining human serum proteins with Remazol Brilliant Blue and separation by disc electrophoresis. PMID- 2578337 TI - Comparison of improved precipitation methods for quantification of high-density lipoprotein cholesterol. AB - We compared the standard Lipid Research Clinics heparin-Mn2+ (46 mmol/L) method and five improved precipitation methods for quantification of high-density lipoprotein (HDL) cholesterol. Three of these methods--a dextran sulfate-Mg2+ procedure, reported as a Selected Method, a modified heparin-Mn2+ (92 mmol/L) method, and a modified phosphotungstate-Mg2+ procedure--all gave similar results. Three other methods--the standard heparin-Mn2+ (46 mmol/L) method and two polyethylene glycol methods (75 g/L or pH 10 reagent at 100 g/L final concentrations)--gave slightly higher values for HDL cholesterol. Addition of NaCl or glucose to specimens did not significantly change protein precipitation. In terms of sedimentation effectiveness with hypertriglyceridemic specimens, the methods were ranked in the following order: polyethylene glycol (pH 10, 100 g/L) greater than dextran sulfate-Mg2+ greater than heparin-Mn2+ (92 mmol/L) = polyethylene glycol (75 g/L) greater than phosphotungstate-Mg2+ greater than heparin-Mn2+ (46 mmol/L). PMID- 2578339 TI - Laser microprobe mass analysis: a tool for evaluating histochemical staining of trace elements. PMID- 2578340 TI - The role of xenoantigen in the human autologous mixed lymphocyte reaction: ability to respond in the absence of exposure to xenoantigen depends on the method of T-cell preparation. AB - Recent reports have suggested that the autologous mixed lymphocyte reaction (AMLR) is attributable to contaminating xenoantigen. T-cell populations separated from peripheral blood mononuclear cells (PBM) over Percoll fail to produce an AMLR in the absence of xenoantigen. However, T-cell populations that do not adhere to plastic and to nylon wool will in the absence of added xenoantigen produce an AMLR comparable to that obtained with E-rosetted populations. In the nonadherent cells separated sequentially by passage through nylon wool and Percoll, the presence of two lymphocyte subpopulations was demonstrated. One is xenoantigen dependent, the other xenoantigen independent in the AMLR. Further, the xenoantigen-independent population may provide help to the dependent population. In the previous reports with Percoll-separated cells that attributed the AMLR to contaminating xenoantigen, the xenoantigen-independent T-cell population was excluded from the responding fraction. PMID- 2578341 TI - Factors controlling the DNA-synthesis in 3T3 and EAT cells. AB - Beta globulins, (Cohn Fr. III), are a major source of molecules affecting the DNA synthesis of 3T3 and EAT cells. Growth inhibitors for both cell types, chromatograph at the same position, corresponding to a mol. wt of about 50,000. A very basic, (pI 10.1), factor is isolated by gel electrofocusing, which stimulates the DNA-synthesis of 3T3 and EAT cells. Because of its extremely high cationic charge and its adsorption on gels, the estimation of the exact molecular weight and its preparative isolation, becomes very difficult. Some of the above mentioned molecules are heat-stable and express their action even after boiling for 10 min at pH 3. PMID- 2578342 TI - Biochemistry of human alpha amylase isoenzymes. AB - The purpose of this article is to review recent literature on the isoenzymes of alpha amylase. Although some studies are cited from the literature of fields other than clinical biochemistry, the aim is to bring together findings that may be of interest to clinical laboratory physicians and scientists. It is hoped that this will be useful in suggesting further studies of amylase. To this end, the review is more selective than exhaustive. The review will discuss the history and chemistry alpha amylases, the measurement of amylase and amylase isoenzymes, posttranslational modifications of human amylases, and the genetics of human pancreatic and salivary amylases. Finally, we will discuss other tissue sources of amylase with emphasis on "genital" amylases and their relationship to the amylase found in serous ovarian tumors. PMID- 2578343 TI - Making title slides: a guide for physicians. AB - Using modern photographic equipment, new Kodak Vericolor slide film, and a little know-how, physicians can produce their own title slides for use in lectures. Slide-making is both easy and inexpensive. A step-by-step approach is outlined herein. PMID- 2578344 TI - Identification of inverted duplicated #15 chromosomes using bivariate flow cytometric analysis. AB - A dual laser FACS IV cell sorter has been used to obtain bivariate flow histograms of human metaphase chromosomes stained with the DNA-specific dyes, 33258 Hoechst and chromomycin A3. Approximately twenty distinct chromosomal fluorescence populations can be resolved using this double staining technique and the flow cytometer which has been modified only by the substitution of a specially designed air-spaced achromat for the standard focusing lens. Metaphase chromosomes from two different cell lines bearing inverted duplicated #15 autosomes have been subjected to bivariate chromosome analysis. In both cases, the inverted duplicated #15 chromosomes have been identified in the bivariate flow histogram. This identification was supported by experiments in which doubly stained chromosomes were counterstained with either netropsin or distamycin A, resulting in a relative increase in the 33258 Hoechst fluorescence intensity of the structurally abnormal #15 chromosomes, compared with the other chromosomes, as predicted by cytological studies. The possibility of identifying and separating small abnormal autosomes using commercially available instrumentation should facilitate the use of recombinant DNA techniques for the construction of libraries which are highly enriched for DNA sequences from limited autosomal subregions important in the study of chromosomal abnormalities such as deletions, translocations and inversion duplications. PMID- 2578346 TI - [Physiological proteinuria in the newborn]. AB - The levels of the individual proteins albumin, caeruloplasmin, immunoglobulin G, and alpha 2-macroglobulin were determined by Laurell's electroimmunoassay in the serum and urine of 127 children. Their age ranged from 29 gestational weeks to 13 years. Highest levels of the proteins in the urine were found during the first days of life. The values did not depend on gestational age. The urine concentrations are influenced by glomerular filtration and the reabsorption of proteins and water. The steady state of these functions can be characterized by the serum/urine concentration ratios and the clearance of the proteins. In the first days after birth the permeability of the renal barrier is maximal, the concentration ratios are low and increase markedly up to the end of the first three months; after that, they continue to rise only slightly. The clearances of all the examined individual proteins decrease between term and the third month of life, thereafter increasing until late childhood. The selectivity of the glomerular filtration also shows its highest rate of development during the first days after term. PMID- 2578347 TI - Quantitative analysis of occipital EEG in different stages of Alzheimer's disease. AB - EEG frequency analysis by Fast Fourier Transform (FFT) was studied in different stages of Alzheimer's disease (AD), defined according to the neuropsychological test score. It was observed that in mild AD the percentage power of the theta band, the ratio of powers in the alpha and theta bands and the mean frequency (range 1.46-20.02 c/sec) differed significantly from the old healthy controls. The percentage power of the alpha band, the occipital peak frequency and the ratio of powers in the alpha and delta bands decreased linearly in different stages of AD. These variables did not differ significantly in mild AD from the control values. Distinct slowing of the occipital peak frequency and distinct accentuation of the percentage power of the delta band occurred in advanced AD. Slowing of the dominant occipital rhythm and accentuation of the diffuse irregular slow waves, which are usually regarded as the main EEG criteria for AD, do not describe mild but advanced disease. PMID- 2578348 TI - Electrophysiological studies of myoclonus in sialidosis type 2. AB - Electrophysiological investigation was performed in 3 patients with beta galactosidase and sialidase deficiencies (sialidosis type 2) in order to elucidate the underlying mechanism of intention myoclonus. It is a rare neuronal storage disease that begins in childhood with mental retardation, skeletal abnormalities, progressive myoclonus and cherry-red spots in the macula. Electrophysiological studies showed paroxysmal activities in the EEG, consistent temporal relationship between the EEG spikes and myoclonic jerks demonstrated by jerk-locked averaging, high amplitude somatosensory evoked potentials with altered wave form, and enhanced long-loop reflexes. These results suggest that there is a hyperexcitability of the cerebral cortex, which results in induction of intention myoclonus. The intention myoclonus in sialidosis type 2 is consistent with 'cortical reflex' myoclonus described in progressive myoclonic epilepsy due to various etiologies. PMID- 2578349 TI - Neurophysiological signs of brain damage due to glue sniffing. AB - Recordings of the brain electrical responses to pattern reversal (checkerboard) visual stimuli showed significantly increased latencies in a group of 12 young people who had been sniffing glue over a prolonged period. Only small improvements were observed in two people who had repeat recordings after 6 months' abstinence. These results show that chronic glue sniffing can lead to long lasting brain damage. PMID- 2578345 TI - Effect of chronic ethanol consumption on the pancreas of the hamster. AB - The purpose of this study was to determine the effect of chronic ethanol consumption on pancreatic morphology and biochemistry in the hamster, with special attention to lipid changes. A control group of Syrian golden hamsters fed a synthetic liquid diet was compared to an ethanol group pair-fed the same diet with ethanol substituted for 35% of the carbohydrate calories. The animals were sacrificed at 7 weeks and 3, 6, 9, and 12 months. After 12 months of ethanol consumption, a significant decrease in pancreatic triglycerides and a significant increase in pancreatic RNA was seen. These changes were associated with a rise in pancreatic weight and protein content in the ethanol group, reversing a six-month decline in these values. This rise in RNA and protein in the ethanol-treated group corresponded with the appearance of large abnormal zymogen granules. Other ultrastructural features such as lipid droplets, mitochondria, and endoplasmic reticulum were not altered by ethanol. Ethanol did increase the water content of the pancreas. Although ethanol had no effect on the fasting levels of insulin or pancreatic polypeptide, the fasting serum gastrin immunoreactivity was significantly lower in the ethanol animals. This study shows that chronic ethanol consumption produces a metabolic change in the hamster by 12 months which is suggestive of increased protein synthesis with a decrease in pancreatic triglycerides and no lipid droplet formation. PMID- 2578350 TI - Somatosensory evoked potentials in abetalipoproteinemia. AB - Visual, brain-stem auditory, and somatosensory evoked potentials (SEPs) were obtained on a patient with known abetalipoproteinemia. Only the SEP was abnormal, and it correlated with the reported neuropathology of this disease. Serial SEP studies remained stable, as had the clinical condition of this patient on vitamin E therapy. The SEP may supplement clinical examination in follow-up of patients under treatment. PMID- 2578351 TI - Pattern of electrical activity and force in normal and pathological muscle: S index of turns and amplitude. AB - Cenkovich et al. (1982) found that a rotated hyperbolic curve fitted the relationship between the logarithm of cumulative amplitude (log A) and the logarithm of turns (log T). They found the intercept of the hyperbola (S-index) to be independent of force and suggested to use the S-index without measurement of the force as a diagnostic criterion. We have applied this modification of the method to our material previously published. In controls we found a slight increase in S-index with increasing force. The S-index was often increased in patients with myopathy and decreased in patients with neurogenic disorders, mostly at low to moderate force. The S-index was not better in discriminating patients from controls than the ratio of turns to mean amplitude. PMID- 2578353 TI - Locomotor limb synergism through short latency afferent links. AB - Reports of facilitation of lower limb synergists through afferent stimulation in resting humans lead to study of short latency reflex responses during activity of the legs. Four synergistic muscles of the right leg were examined following electrical stimulation of low threshold afferents of the posterior tibial (PTN) and femoral (FN) nerves. Four males cycled on an ergometer with pedals modified to measure the force applied. Movement frequency was 0.8 Hz with 15 N ergometer resistance for two 6 min trials, one involving PTN and the other FN. Collection of EMGs of soleus, lateral gastrocnemius, vastus medialis and rectus femoris lasted for 200 msec after stimulation, which was triggered when the pedal was 56 degrees beyond top-dead-center. Control EMGs were similarly collected during intervening, non-stimulated, pedal cycles within the same work bout. Collection of force on pedals occurred over the same 200 msec period as well as the following two complete pedal revolutions. From PTN stimulation short latency increase occurred not only in homonymous EMGs but also in heteronymous as distant as rectus femoris. FN stimulation similarly resulted in short latency changes in quadriceps and also in triceps surae. Pedal force changes accompanied the EMGs. M response confounding in many cases resulted in only tentative identification of the reflex force evoked. Little change with stimulation was seen in the force in subsequent cycles. The responses represent a net of pathways which could affect within-limb coordination of muscles during human locomotion and extend previous investigations of Ia projections in spinal cats and resting humans. PMID- 2578352 TI - Sleep EEG effects of exercise with and without additional body cooling. AB - The aim of the study was to help clarify the equivocal findings with slow wave sleep (SWS) stages 3 and 4, following running in physically trained individuals. Six females (22-24 years) ran at 75% of their VO2max for 2 X 40 min periods on two separate occasions, 14.30-17.30 h: once under hot conditions, causing a rectal temperature (Tr) increase averaging 2.3 degrees C, and once with additional cooling, reducing the Tr rise to an average of 1.0 degree C. Compared with baseline nights, no significant sleep effects were found on the cool run. However, after the hot run, SWS, particularly stage 4 sleep, showed significant increases, and REM sleep was decreased. It was concluded that body heating effects during running may play a key role in SWS changes, and that additional cooling seems to eliminate any potential SWS increase. PMID- 2578354 TI - Hippocampal theta rhythm during paradoxical sleep. Effects of afferent stimuli and phase relationships with phasic events. AB - Hippocampal theta rhythm and phasic events (i.e., vibrissa, body and ocular movements and ponto-geniculo-occipital (PGO) spikes) were recorded in rats and cats during paradoxical sleep (PS). Single pulse stimulation of some afferent structures (i.e., medial septum, mesencephalic reticular formation and entorhinal cortex) were performed during PS. Hippocampal afferent stimulation determined the phase resetting of hippocampal theta waves during PS in a similar form to that during wakefulness. All studied phasic events tend to occur at a preferred phase of the theta cycle. Theta waves begin to synchronize some time before movements. These results suggest that PS is an active state during which hippocampal theta rhythm may have functions similar to those occurring during wakefulness, e.g. sensorimotor integration. PMID- 2578355 TI - Threshold of synaptically elicited cortical spreading depression: drug-induced changes in rats. AB - The role played by synaptic phenomena in the initiation of Leao's spreading depression (SD) was examined in 30 rats anaesthetized with pentobarbital. SD was elicited by a train of 8 electrical pulses (0.1-0.3 msec, 10 Hz) applied through bipolar electrodes to the exposed cortical surface. The slow potential waves of SD were recorded from the stimulated site and from a remote cortical area. Threshold stimulus intensity (40 V) was increased above 80 V when low frequency stimulation (0.3 Hz, 10 V) was applied through the same electrodes. SD penetration into the stimulated area was blocked with higher stimulus rates (3-10 Hz) and intensities (20 V). Systemic application of the pyrrolopyrimidine drug BE 58-271 decreased SD threshold from 40 V to 7 V and reduced also the intensity and frequency of stimulation inducing the SD blockade. Similar effects were obtained with local application of 2 microliters of 10(-3) M 4-amino-pyridine to the stimulated cortex. The SD threshold was reduced from 40 V to 5 V, probably by prolonged depolarization of axon terminals and increased output of transmitters. Estimation of SD threshold revealed a biphasic effect of locally applied penicillin: an initial threshold decrease which gradually changed with the development of regular interictal discharge into a threshold increase and eventual SD blockade. It is concluded that sudden synaptic activation of cerebral cortex elicits SD whereas prolonged continuous stimulation decreases SD susceptibility, probably by enhancing the K+ clearance. PMID- 2578357 TI - Electrophysiologic studies in neonatal adrenoleukodystrophy. AB - Recent electrophysiologic studies have focussed attention on the X-linked adrenoleukodystrophy (ALD) and its myeloneuropathic variant. No organized studies are, however, yet available on its relatively recently described neonatal variant. We conducted electroencephalographic, electroretinographic and evoked response studies in 2 patients with neonatal ALD. In one patient, an infant, initial EEG, hypsarrhythmic in waking and somewhat periodic in sleep, showed dramatic improvement on ACTH therapy accompanied with a seizure-free status. The EEG and clinical improvement, however, were temporary. No improvement occurred following pyridoxine therapy. Her electroretinogram (ERG), visual evoked responses (VERs) and far-field short latency brain-stem auditory evoked responses were also abnormal. The latter studies probably reflected photoreceptor degeneration, optic nerve involvement, cochlear and/or auditory nerve involvement respectively in neonatal ALD. The other patient, a 3.5-year-old girl, also had an EEG characterized by a moderate- to high-amplitude slow background activity and high-amplitude multifocal, generalized or periodic paroxysmal discharges, but presence of some better formed theta frequencies in background activity precluded a hypsarrhythmic label on her EEG. Her ERGs and VERs were totally extinct but in contrast to the first patient, she had clear-cut optic atrophy and retinitis pigmentosa on ophthalmological examination. PMID- 2578356 TI - Spectral analysis of hippocampal EEG in the freely moving rat: effects of centrally active drugs and relations to evoked potentials. AB - Hippocampal EEG signals derived from chronically implanted electrodes in the freely moving rat were recorded before and after administration of centrally acting drugs, and analyzed by power and coherence spectra. Eserine, ether or urethane induced a low frequency (3-6 c/sec) theta power and coherence peak in the immobile rat, which was sensitive to atropine or scopolamine. After phencyclidine, theta that occurred during walking (7-8 c/sec) was virtually abolished by atropine while in the normal rat, absolute theta power was not affected by atropine. The residue spectrum, defined as the EEG spectrum with the theta harmonics removed, was sensitive to centrally acting drugs. Ether, urethane and pentobarbital suppressed fast waves of 50-100 c/sec, and under some conditions, enhanced 15-50 c/sec waves. Eserine enhanced (30-60 c/sec) fast waves during walking while atropine suppressed fast waves and increased irregular slow activity (less than 30 c/sec). The main effects of drugs and behavior on the residue spectra and on the average evoked potentials following stimulation of the Schaffer collaterals could be explained by a previously proposed model (Leung 1982) which suggests a continuum of hippocampal 'activation' (tonic input) under the various conditions. PMID- 2578358 TI - A method for chronically recording brain-stem and cortical auditory evoked potentials from unanesthetized mice. AB - Anesthetizing or sedating animals affords control over movement artifact during electrophysiological recording. However, the use of chemical restraint leads to unwanted side effects such as drug-induced hypothermia. Hypothermia is problematic because BAEP amplitudes and latencies are affected significantly by core temperature changes. Moreover, several recent studies have indicated that anesthetics and sedatives may significantly alter the BAEP and CAEP even in thermoregulated subjects. There is a need, therefore, to develop a practical technique for obtaining chronic BAEPs and CAEPs in restrained, unanesthetized animals. The present report describes a technique that permits the gathering of consistent, reliable evoked potential recordings over time in unanesthetized mice. The preparation is useful for studying the CNS effects of pharmacological agents, pathological conditions, aging and development in the mouse and could be adapted for use with other small animals as well. PMID- 2578359 TI - Quantitative analysis of 'organization' by feature extraction of the EEG power spectrum. AB - Quantitative analysis of 'organization' of the background EEG activity was made by applying a new method of approximating the optimal intensity-fitting function to the EEG records of healthy college students. The parametric intensity-fitting function used in this study to approximate the power spectrum of EEG was a gaussian type function. Among the quantitative parameters obtained by the new method, the ratio of the integrated power of alpha rhythm to that of all rhythms and the standard deviation of the alpha frequency proved to be the most important organization parameters by inspecting the Pearson product-moment correlation coefficient. Next the automatic scoring of 'organization' was successfully performed by using the linear regression of those two organization parameters. PMID- 2578360 TI - Instantaneous frequency meter with averaging capability based on interval duration measurement. AB - The instantaneous frequency meter described uses an inexpensive hybrid module for on-line interval to frequency conversion and also has a digital low pass filter function. The device is not only a frequency to voltage converter but also is well suited to serve as an interface to a digital computer. PMID- 2578361 TI - Postalcoholic diseases: diagnostic relevance of computerized EEG. AB - In 48 patients with sequels of chronic alcoholism automatically analysed EEGs were taken twice: (1) some 2 days after cessation of acute delirious or predelirious states; (2) some 18 days later, after clinical recovery. EEG results were supplemented by neuropsychological, biochemical and clinical data. Complementary analyses in the time (Hjorth's descriptors) and frequency (spectral analysis) domains at the first time operationally identified EEG correlates of a hallucinatory syndrome vs. personality deterioration ("depravation'), together with specific effects of drinking habits and withdrawal. The second examination disclosed prognostically different types of EEG reactions to chronic alcoholism. PMID- 2578362 TI - Visual evoked potentials (VEPs) in senile dementia (Alzheimer type) and in non organic behavioural disorders in the elderly; comparison with EEG parameters. AB - Forty-two patients with senile dementia of the Alzheimer type were compared with normal subjects (51) and with elderly patients with nonorganic psychiatric disorders (40). All were examined by EEG (routine visual inspection and power spectrum density analysis) and VEP (pattern reversal) testing. In dementia the late components (N130, P165, N220) of the VEP are delayed, but the EEG was abnormal more often than the VEP. PMID- 2578363 TI - Click spatial position influences middle latency auditory evoked potentials (MAEPs) in humans. AB - Middle latency auditory evoked potentials (MAEPs) were elicited by monaural and binaural clicks. The Na component (latency 15.8 msec) was larger in amplitude and shorter in latency at electrodes contralateral to the stimulated ear in monaural conditions, but showed no evidence of binaural occlusion. The Pa (28.4 msec) and Nb (42.0 msec) components did not change in amplitude or distribution as a function of the ear of stimulus delivery, but were smaller following binaural stimulation than would have been predicted from separately recorded monaural responses. These results indicate that functionally distinct generator systems are responsible for different components of the MAEP. The generators of the Na are more effectively activated by contralateral inputs. In contrast, the generators of the Pa and Nb receive equally effective and convergent inputs from the two ears. PMID- 2578364 TI - The relationship between mean power frequency of the EMG spectrum and muscle fibre conduction velocity. AB - Models of the behaviour of the surface EMG signal during fatigue have assumed that there is a linear relationship between the mean power frequency of the EMG spectrum and muscle fibre conduction velocity. They attribute the fall in mean power frequency during fatigue to a proportionate fall in fibre velocity. Experiments have been performed on human vastus lateralis in which forces ranging from 10% to 90% of the maximum force were sustained for times such that the product of the target force and the time was constant. Muscle fibre conduction velocity was estimated using a cross-correlation technique to determine the lag between two EMG signals. The results confirmed the linearity between mean power frequency and fibre velocity. It is still possible, however, that other factors such as de- and recruitment of fibres and change in motor unit firing rates contribute to the fall in mean power frequency during fatigue. Even if these factors are important, the primary assumption of current EMG models relating mean power frequency and muscle fibre velocity has been confirmed. PMID- 2578365 TI - Movement related slow potentials. II. A contrast between finger and foot movements in left-handed subjects. AB - Finger and foot movement related potentials (MRPs) were recorded over the frontal, central and parietal areas of both hemispheres in 20 left-handed subjects. A unilateral flexion of the index finger and a plantar flexion of the foot were studied on either side. MRPs were larger preceding foot movements than preceding finger movements, their onset being earlier also. Prior to a finger flexion amplitudes were larger over the hemisphere contralateral to the movement than over the ipsilateral hemisphere. Preceding a foot movement, however, amplitudes were larger over the ipsilateral hemisphere. These results indicate differently localized sources of the MRPs in the two kinds of movement, in accordance with data obtained in right-handed subjects. No indication of a hemisphere effect, possibly related to motor dominance, was found in left handers. This is in contrast to a slight hemisphere effect found with foot movements in right-handed subjects in the former study. PMID- 2578366 TI - Effects of body temperature elevation on auditory nerve-brain-stem evoked responses and EEGs in rats. AB - ABRs and EEGs were recorded in anaesthetized rats during whole body hyperthermia. ABR amplitudes were decreased during warming, with little recovery as body temperature was lowered. The latencies of the ABR waves decreased with warming and increased with subsequent cooling. The major latency changes were in the later ABR waves. Warming was accompanied by suppression of the EEG. These results point out that ABR evaluation of patients must take into account elevated body temperatures. Since it has been shown that the rat can serve as a model of the effects of heat on man, an attempt is made to relate these ABR and EEG findings in rats to studies of human psychomotor performance during heat exposure. PMID- 2578367 TI - Night-time sleep EEG changes following body heating in a warm bath. AB - Six healthy female volunteers (22-24 years), physically untrained (unfit), sat in baths of warm or cool water for 90 min, between 14.30 h and 17.30 h, on separate occasions. In the former condition (HOT), rectal temperature (Tr) rose by an average of 1.8 degrees C, and in the latter (COOL), a thermoneutral condition, there was a nil Tr change. All-night sleep EEGs were monitored after both occasions and on baseline nights. Following COOL, there was no significant change in any sleep parameter. After HOT there were significant increases in: sleepiness at bed-time, slow wave sleep, and stage 4 sleep. REM sleep was reduced, particularly in the first REM sleep period. PMID- 2578368 TI - Physiological sleep myoclonus in baboons. AB - Physiological sleep myoclonus (sleep onset myoclonus and myoclonus during paradoxical sleep) was recorded from the tails of 6 baboons (2 Papio hamadryas and 4 Papio papio) and its relationship with spontaneously occurring EEG paroxysmal discharges was studied. It was observed that during light slow wave sleep tail myoclonus (sleep onset myoclonus) was almost always associated with EEG paroxysmal discharges predominating in the fronto-rolandic cortex. During deep slow wave sleep the number of EEG paroxysmal discharges decreased and tail myoclonus disappeared. In contrast, during paradoxical sleep tail myoclonus became more frequent even in the absence of cortical paroxysmal discharges. Though at present we do not know whether sleep onset myoclonus is triggered or not by cortical paroxysmal discharges, we propose that sleep myoclonus (sleep onset myoclonus and myoclonus of paradoxical sleep) is independent of these discharges but that, at a given moment, the two phenomena may be coupled by a hypothetical subcortical pacemaker. PMID- 2578370 TI - A general-purpose automatic multichannel electronic switch for EEG artifact elimination. AB - A general-purpose automatic multichannel electronic switch is described for eliminating artifact from EEG recordings. Although primarily intended for computer processing of EEG data, the device may on occasion be useful in clinical EEG (e.g., during electro-cautery). The switch is activated from a separate artifact-monitoring channel of the electroencephalograph (e.g., accelerometrically monitored head movement, electro-oculographically monitored eye movements or blinks), or from an EEG channel itself, if the artifact in the latter is very marked. Optionally, a sine wave can replace the EEG during the artifact period, and a separate output signal (e.g., for interrupting computer processing) is available for indicating the occurrence of artifact. PMID- 2578369 TI - Computer characterization of trace alternant and REM sleep patterns in the neonatal EEG by adaptive segmentation--an exploratory study. AB - The possible utility of the computer technique of adaptive segmentation in the comparative quantitative characterization of trace alternant (TA) and REM sleep in the neonatal EEG has been explored in a pilot study of the EEGs of 3 full-term infants of ages 1, 13 and 23 days. The technique of adaptive segmentation, originally developed by its authors for automatically delimiting and characterizing different types of patterns within the same EEG recording, had previously been found effective for this purpose for normal and abnormal adult EEGs. The same computer program parameter values that had been found to be optimal for segmentation of adult EEGs were also found to be optimal for the neonatal ones, as typified by segmentation or demarcation of the bursts and interburst periods in trace alternant. Adaptive segmentation, in conjunction with clustering of the resulting segments and computation of temporal profiles showing the times of occurrence of the different types of activity in a given phase of sleep together with the mean amplitude and mean frequency of each, supplemented by the respective power spectra, was found to be an effective way of characterizing these EEGs, including certain types of artifact. Further characterization was afforded by statistical summaries of segment durations. PMID- 2578371 TI - Multichannel data acquisition system for recording the acoustic brainstem response. AB - A system has been developed to sample and average multi-channel ABR data. All channels are sampled simultaneously. The simple design incorporates one sample and-hold amplifier and one analog-to-digital converter in each channel. For sampling of 13 channels or less, sampling interval must exceed 36 microseconds for full 10-bit resolution. For sampling more than 13 channels, data transfer to the host computer limits minimum sampling interval to 20 + (1.2 X N) microsecond, where N is the number of channels sampled. PMID- 2578372 TI - The EEG of the early premature. AB - EEGs were taken of 33 premature babies of 27-32 weeks of conceptional age who were considered normal for their conceptional age by clinical criteria. The EEGs were divided into epochs of 1 min each and their characteristics of temporal and spatial organization as well as amount and distribution of special patterns were coded and analyzed. The records were mostly discontinuous, with synchronous and symmetric bursts. There was much rhythmic activity in all frequencies and some patterns were consistently asymmetric. At least one pattern, the sawtooth, seems to be characteristic of this early conceptional age. Follow-up EEGs and clinical examinations were done on 17 children at 6-8 months of age post term. Three more died before 6 months and on one a telephone report was obtained from the mother. The characteristics of the neonatal EEGs were compared with those published on smaller groups of early prematures and those on later premature babies. PMID- 2578373 TI - Color imaging of parietal and frontal somatosensory potential fields evoked by stimulation of median or posterior tibial nerve in man. AB - Somatosensory evoked potentials (SEPs) to median or fingers or posterior tibial nerve stimulation were recorded with earlobe reference in normal young adults. A system of 16 electrodes on the scalp served to create bit-mapped images of the potential fields at 1 msec intervals. The P14 (median SEP) or P30 (tibial SEP) far fields thought to reflect the afferent volley in the medial lemniscus produced widespread positivity over the scalp. Subsequent components had a characteristic focal distribution suggesting that they reflected one or more generators in cortical areas. For the median SEP, the parietal N20 and the prerolandic P22 showed differences in onset and offset times as well as distribution that precluded their being related to the same generator. While N20 was contralateral, P22 extended ipsilaterally. P22 may be generated in the motor area 4 and the supplementary motor area. P22 was also distinct from the P27 field restricted to the contralateral parietal region. The frontal N30 had a bilateral distribution and the P45 presented variable features. For the tibial SEP, no phase reversal was confirmed between the parietal P38 (midline-ipsilateral focus) and N33 (contralateral focus). N37 over the contralateral prerolandic region might reflect a generator in the motor region. P58 was more symmetrically distributed than P38, possibly because it reflected generators more posteriorly on the parietal convexity. N75 had a widespread field with focus on the ipsilateral side of midline. PMID- 2578374 TI - Multimodality evoked potentials in patients and carriers with adrenoleukodystrophy and adrenomyeloneuropathy. AB - A combination of brain-stem auditory evoked potentials (BAEPs), short latency somatosensory evoked potentials (SEPs) and pattern reversal visual evoked potentials (VEPs), were studied in two patients with adrenoleukodystrophy (ALD) and one patient with adrenomyeloneuropathy (AMN), as well as in one female carrier of each of the respective diseases. Abnormalities in at least 1 of the 3 evoked potentials were found in every case, including the carriers of ALD and AMN. The two most common findings were prolongation of the I-V interval of the BAEP and the N13-N20 interval of the SEP. These abnormalities were recorded either alone or in combination in all 5 cases. This finding suggests delayed conduction time in the central sensory pathways in both diseases, probably due to demyelination. The remarkable result, which distinguished AMN from ALD, even in their respective carriers, was delay of the N9 latency of the SEP, indicating slowing in conduction velocity of the peripheral nerve. Multimodality evoked potentials are useful not only in raising the detection rate for abnormal findings, but also in providing additional information about the functional state of separate afferent pathways. It is also of value in detecting and differentiating the carriers of ALD and AMN. PMID- 2578375 TI - Effects of expectation on negative potentials during visual processing. AB - ERPs were recorded during several RT tasks: simple RT; oddball choice RT; a LIE condition in which subjects were told stimuli would infrequently change, but did not; differential responding to two equiprobable stimuli that were randomized in one condition and alternated in another condition. Subtracting ERPs elicited during simple RT from those elicited during the other conditions, it was found that a negative component, NA, was enhanced, relative to simple RT, in all the other RT tasks. The data of the LIE condition indicated that NA was enhanced by the expectation that unpredictable stimulus changes would occur, even when they did not. The data of the 50/50 alternating RT condition indicated that stimulus changes by themselves enhance NA, even when they are predictable. There appear to be several deflections that comprise NA. NA was obtained with a variety of subtractions that balanced stimulus probability, the structure of the stimulus sequence and task instructions. Similar results were obtained whether subjects made a finger lift response or counted stimuli. PMID- 2578376 TI - Two bilateral sources of the late AEP as identified by a spatio-temporal dipole model. AB - A new spatio-temporal dipole model is presented, which enables prediction and analysis of scalp potential wave forms due to spatio-temporal overlap of multiple generators. Each generator is thought to represent a local neural subset, the electric activity of which can be modelled by an equivalent dipole with stationary location and orientation closely related to the spatial organization of the neural subset. The temporal course of dipole magnitude is assumed to depict the external far field due to the compound discharge processes of the generator. Simulations of uni- and bilateral dipoles within the temporal lobe, oriented vertically and horizontally, demonstrate how spatio-temporal overlap mag bring about the 'vertex response' of the late AEP and the wave form changes observed over temporal sites. Analyses of late AEPs reported for a coronal chain of electrodes by Peronnet et al. (1974) and Vaughan et al. (1980) revealed that the wave forms in the 60-250 msec range could be perfectly matched at all electrodes by model wave forms due to 2 bilateral sources within the temporal lobe. Their locations, orientations and their latency difference of about 30 msec suggest consistently that the sequential activation of primary and secondary auditory cortices is the predominant source to the late AEPs. PMID- 2578377 TI - Somatosensory evoked potentials in minor cerebral ischaemia: diagnostic significance and changes in serial records. AB - Frontal, central and parietal short and middle latency somatosensory evoked potentials (SEPs) arising after stimulation of the contralateral median nerve were studied in 10 normal adults. Stable SEPs were recorded: a frontal P21-N30 complex and an N20-P23-P28-N35-P42 complex in the centro-parietal region. The use of a chin reference electrode allowed identification of (the thalamic) P15 and N18. SEP studies of 20 patients with unilateral cerebral ischaemia were also performed, about 4 and 18 days after the stroke. In 13 out of 18 patients with a minor stroke (TIA, RIND and PNS) abnormalities of the frontal and/or parietal SEPs were demonstrated. Improvement in these SEPs occurred in 5 cases. In two patients who suffered from a major ischaemic deficit, the SEPs were highly abnormal and did not show any change in the course of time. SEP studies may be useful for the diagnosis of minor cerebral ischaemia as well as quantification of recovery; an even more important indication for this neurophysiological method might be detection of subclinical lesions in patients who have suffered from transient cerebral ischaemia even weeks before the SEP studies are carried out. PMID- 2578378 TI - Binaural interaction in auditory brain-stem responses: effects of masking. AB - Binaural interaction (BI) in auditory brain-stem responses (ABRs) can be shown by comparing a binaurally elicited ABR to the algebraic sum of monaurally elicited ABRs. Subtracting the summed monaural ABR from binaural ABR yields a wave form assumed to contain response components attributable to BI. It has been suggested that acoustic crosstalk accounts for some of the 'BI' seen with this technique and that contralateral masking should be used during monaural stimulation to eliminate crosstalk. However, this practice might in itself confound the results, even if the masking noise were not intense enough to affect the opposite ear, by 'central masking' of brain-stem neural activity. We studied the effects of contralateral wide-band masking on BI/ABR in 10 normal adult subjects. Clicks were presented at levels from 55 to 115 dB peSPL, at 10 dB intervals. Masking was presented at 73 dB SPL (47 dB effective masking level); based on pilot studies of interaural attenuation, this was a level expected to be at, or just below, the threshold of audibility in the contralateral ear. BI/ABR wave forms were not noticeably affected by the addition of contralateral noise in the monaural trials. In addition, BI/ABR was seen (as previously reported) at levels well below any possibility of crossover artifact. Thus, BI/ABR is not simply attributable to crossover. Contralateral masking is not necessary in recording BI/ABR, within the limits of the stimuli and transducers used in this study. PMID- 2578380 TI - Source derivation of the visual evoked response to pattern reversal stimulation. AB - This study demonstrates that the source derivation procedure described by Hjorth (1975) reveals lateralisation of the visual evoked response to pattern reversal stimulation in accord with the anatomical data. PMID- 2578379 TI - Non-linearity of visual evoked potentials in cerveau isole and midpontine pretrigeminal cats. AB - Characteristics of the visual evoked responses to the flickering flash stimulation were studied in the cerveau isole and midpontine pretrigeminal cats. The flash stimulation frequency was changed stepwise between 1 and 30 Hz in increasing and decreasing order. In all cases of both preparations, with drawing of fixed sweep speed of 200 msec in whole length, P1 and N1 latencies in the successive response slightly prolonged progressively 1 to about 20 Hz and thereafter shortened about 20-30 Hz stimulus frequencies in the course of the increasing phase, and vice versa in the course of the decreasing phase. Moreover, no difference in each latency (P1, N1, P2, N2) was found at the same stimulus frequency during increasing and decreasing phases. In the amplitude taken from the P1-N1 component, the peak was found in 5-9 Hz frequency bands. This peak was higher during the decreasing phase than during the increasing phase, which indicated a hysteresis phenomenon. A peak of power for the 1st harmonics was found at 3-6 Hz driving frequency bands, and that of the 2nd harmonics at 6-10 Hz. In the state without flash stimulus, no peaks or valleys in the power spectrum were found in specific frequencies, for example 3-10 Hz. The peak in the amplitude and that in the power spectrum at 3-10 Hz stimulus frequency bands suggested an entrainment phenomenon induced by forced oscillation. The phenomena of entrainment and hysteresis suggest the existence of a non-linear structure in the oscillation generating systems of visual evoked response. PMID- 2578381 TI - Changes in flash but not pattern evoked cortical potentials after subchronic application of a monoamine oxidase (MAO) type A inhibitor in man. AB - Changes in flash but not pattern evoked cortical potentials after subchronic application of the MAO type A inhibitor pirlindole in man are reported. Pirlindole affects the deamination of serotonin and noradrenaline in the central nervous system and has serotonin reuptake inhibiting properties. Flash and pattern evoked cortical potentials were recorded in 6 healthy men before and after a 7 day period of treatment with 3 X 75 mg/day of pirlindole. After drug treatment, an increase in P100 latency to flash stimuli was seen without a change in the latency to pattern stimuli. This indicates that different neuronal systems process flash and pattern stimuli. PMID- 2578382 TI - Temporal sequence of prolactin actions on phospholipid biosynthesis in mouse mammary gland explants. AB - Studies were carried out to determine the effect of PRL on the metabolic fate of 32PO4 in cultured mammary gland explants derived from 12 to 14-day pregnant mice. Explants were initially cultured for 24-36 h with 10(-7) M cortisol and 1 microgram/ml insulin. PRL (1 microgram/ml) was then added to certain of the cultures and incubation continued for 2-24 h. Tissues were pulse labeled with 5 microCi/ml 32PO4 during the final 2 h of culture. Tissues were fractionated by the method of Bligh-Dyer. Radioactivity was determined in the organic fraction (containing phospholipids), the aqueous fraction, and an insoluble fraction containing macromolecules. In all these fractions, PRL effected a greater than 2 fold increase in radioactivity content; the onset of the PRL responses was 8-12 h after PRL exposure and PRL effected responses at concentrations of 2.5 ng/ml and above. The enhanced rate of 32P incorporation in the macromolecular fraction was found to occur in both the RNA and phosphoproteins in that fraction. As determined by TLC, PRL was also found to increase 32P incorporation into all phospholipid fractions. This was confirmed by observing that [3H]inositol and [3H]choline incorporation into their respective phospholipids was also increased by PRL; the time sequence of response was similar to that when 32PO4 incorporation was determined. The magnitude of the PRL stimulation of 32PO4 incorporation, however, was about 2-fold higher than either the [3H]inositol or [3H]choline incorporation. The magnified response when 32PO4 was employed may reflect a PRL effect on phosphate uptake into the mammary cells; this is supported by the fact that the radioactive content of the aqueous fraction was significantly elevated in the Bligh-Dyer extract. The effect of PRL on phospholipid synthesis probably reflects the initiation of the packaging process involved in the assimilation of milk products. PMID- 2578383 TI - The effects of maitotoxin on 45Ca2+ flux and hormone release in GH3 rat pituitary cells. AB - Maitotoxin has been reported to activate calcium channels and stimulate calcium dependent functions in several tissues, but a thorough investigation of 45Ca2+ fluxes is lacking. To characterize the influence of maitotoxin on 45Ca2+ flux in greater detail, we incubated dispersed GH3 pituitary tumor cells in 45Ca2+ with maitotoxin and other agents affecting calcium channels. Within 10 sec of exposure, maitotoxin induced a net calcium influx in cells at isotopic equilibrium. Calcium uptake was concentration dependent between 0.4 and 40 ng/ml maitotoxin and was inhibited by antagonists of voltage-dependent calcium channels but not by inhibitors of sodium channels. PRL and GH release from perifused GH3 cells was stimulated within 1 min by maitotoxin. We conclude that maitotoxin causes a rapid, concentration-dependent influx of calcium through presumed voltage-dependent endogenous calcium channels, culminating in enhanced hormone release. This potent toxin may provide a more precise understanding of the role of calcium in the stimulus-secretion coupling process. PMID- 2578384 TI - Evidence for a role for adenosine 3',5'-monophosphate in progesterone secretion by human chorion. AB - Experiments were performed to determine whether cells from human chorion can synthesize and release progesterone. Cells were isolated from term chorion laeve by collagenase-DNAse digestion and incubated in RPMI-1640 medium. Freshly isolated cells contained 9.9 +/- 1.1 ng progesterone/10(6) cells, and released 72.0 +/- 7.1 ng/10(6) cells X 24 h in the absence of precursors. When 25 hydroxycholesterol (25HC) served as a precursor, progesterone release into the medium was concentration and time dependent from 1-20 micrograms/ml up to 8 h. When pregnenolone served as a precursor, progesterone secretion followed Michaelis-Menten kinetics (Km = 6.7 microM; maximum velocity, 1.02 nmol/10(6) cells X h). In the presence of 25HC (20 micrograms/ml), progesterone release increased significantly on exposure to cholera toxin (1 microgram/ml), methylisobutylxanthine (0.1 mM), forskolin (0.1 mM), or (Bu)2cAMP (1 mM). Cells maintained in culture released progesterone when fetal calf serum (10%) or 25HC served as precursors. These studies show that trophoblasts from fetal membranes can synthesize and release progesterone from endogenous and exogenous precurors and support the suggestion that cAMP is an important mediator in this process. PMID- 2578385 TI - Vasoactive intestinal peptide binding to specific receptors on rat parotid acinar cells induces amylase secretion accompanied by intracellular accumulation of cyclic adenosine 3'-5'-monophosphate. AB - Specific binding sites for vasoactive intestinal polypeptide (VIP) were characterized in dispersed rat parotid acini. The binding of [125I]VIP was rapid, saturable, reversible, and temperature dependent. Scatchard analysis indicated two functionally independent classes of receptor sites: 41,000 high affinity-low capacity sites per cell with a dissociation constant (Kd) of 6.4 nM and 420,000 low affinity-high capacity sites per cell with a Kd of 150 nM. A peptide with N terminal histidine and C-terminal isoleucine and secretin, which are structurally related to VIP, inhibited the tracer binding 30 and 200 times less strongly, respectively, than VIP. Epinephrine and carbachol did not inhibit [125I]VIP binding to parotid acinar cells. VIP stimulated cAMP accumulation in parotid lobules and induced amylase secretion in a dose-dependent manner. A peptide with N-terminal histidine and C-terminal isoleucine and secretin were less potent than VIP regarding cAMP accumulation (1/12 and 1/80 of VIP, respectively) and amylase secretion (1/40 and 1/500 of VIP, respectively). Substance P did not stimulate cAMP accumulation but stimulated amylase secretion more strongly than VIP. These observations clearly demonstrated the presence of VIP receptors coupled to adenylate cyclase system in the rat parotid gland, which plays an important role in the regulation of the amylase secretion. The regulation of parotid function by VIP was independent of the adrenergic or muscarinic regulatory system and of the influence of substance P. PMID- 2578386 TI - Morphological and biochemical responses of cultured thyroid cells to thyrotropin. AB - In the thyroid gland, TSH stimulates cAMP formation, exocytosis of precursor (noniodinated) thyroglobulin, endocytosis of thyroglobulin, and proteolytic processing of the thyroglobulin to form thyroid hormones. In this report we describe TSH effects on cAMP levels, microtubules, microfilaments, myosin fibrils, and the morphology of cultured thyroid follicle cells. The cells were normally cultured in the presence of 10 mU/ml TSH, and fresh TSH produced no stimulation when assayed for cAMP production in a 15-min assay. When such cells were cultured for up to 72 h in the absence of TSH and then assayed for cAMP production, the basal levels were much reduced, but fresh TSH stimulated cAMP levels half-maximally at 1 mU/ml and up to 50-fold at 20 mU/ml. Microtubules, myosin fibers, and microfilaments were demonstrated by indirect immunofluorescent staining. Fluorescent staining of fibers was observed in cells fixed before lysis and in cells lysed before fixation. In control cells grown without hormone, microtubules originated near the nucleus and extended to the cell periphery. Myosin-containing fibrils traversed the cell or radiated from foci. Microfilaments spanned the cell in a stress fiber pattern. After incubation with 20 mU/ml TSH and 4 mM isobutylmethylxanthine (IBMX) for 10-20 min, the microtubules in up to half of the cells appeared altered and more granular, and the cell periphery was scalloped. After 15-30 min with TSH and IBMX, normal myosin fibers were replaced with a fine lattice-work, peripheral staining disappeared, and the proportion of nonfibrous myosin increased. Stress fibers demonstrated with antibody to actin also disappeared, and the peripheral structures observed in normal cells became fragmented. Incubation with forskolin or TSH and IBMX for 2-3 h resulted in arborization of 30-60% of the cells that contained bundles of microtubules, myosin fibers, or microfilaments into dendrite like processes and increased staining near the nucleus. At 5 h, more than 80% of the cells were arborized. These morphological changes were less pronounced with IBMX alone and minimal with TSH alone. The time course of cAMP levels observed basally or after TSH, forskolin, or TSH and IBMX was consistent with the relative effects of these agents on arborization. These studies are consistent with effects of cAMP on microtubules, myosin-containing fibrils, and microfilaments and may provide a basis for the morphological response to TSH. PMID- 2578387 TI - The effects of terbium (III) on the Ca-activated, K channel found in the resealed human erythrocyte membrane. AB - Incorporated terbium, Tb3+, activates the Ca-activated K channel found in the resealed erythrocyte ghost membrane and allows the net efflux of K. As in the case of Ca activation, low levels of external K stimulate the net efflux of K. The action of incorporated Tb3+ seems to be analogous to that of incorporated Ca. Externally applied Tb3+, however, inhibits the net efflux of K after either Ca or Tb3+ activation. The net-efflux of K can be inhibited by Tb3+ even after partial digestion of the channel by low levels of incorporated trypsin. Furthermore, the channel when incorporated into planar bilayers, can be inhibited by Tb3+. Externally applied Tb3+ does not seem to inhibit net K efflux indirectly via inhibition of the pathways for the co-transported anions. In addition because of the low concentrations of Tb3+ required for inhibition, it seems unlikely that an alteration of surface potential is responsible for the observed effects. PMID- 2578388 TI - Effects of the ribosomal subunit association on the chemical modification of the 16S and 23S RNAs from Escherichia coli. AB - 70S ribosomes and 30S and 50S ribosomal subunits from Escherichia coli were modified under non-denaturing conditions with the chemical reagent dimethylsulfate. The ribosomal 23S and 16S RNAs were isolated after the reaction and the last 200 nucleotides from the 3' ends were analyzed for differences in the chemical modification. A number of accessibility changes could be detected for 23S and 16S RNA when 70S ribosomes as opposed to the isolated subunits were modified. In addition to a number of sites which were protected from modification several guanosines showed enhanced reactivities, indicating conformational changes in the ribosomal RNA structures when 30S and 50S subunits associate to a 70S particle. Most of the accessibility changes can be localized in double helical regions within the secondary structures of the two RNAs. The results confirm the importance of the ribosomal RNAs for ribosomal functions and help to define the RNA domains which constitute the subunit interface of E. coli ribosomes. PMID- 2578389 TI - Sheep keratins: characterization of cDNA clones for the glycine + tyrosine-rich wool proteins using a synthetic probe. AB - cDNA clones coding for the high-glycine + tyrosine (HGT) proteins of sheep wool keratin have been isolated and sequenced. Clones were identified using a 25-base synthetic oligonucleotide probe, deduced from the amino acid sequence of a HGT protein present at about 0.4% in the wool fibre. Southern and Northern blot analysis suggest that the gene is present as a single copy in the genome and is transcribed as an mRNA species, 600 bases in size. PMID- 2578390 TI - Human plasma actin-depolymerizing factor. Purification, biological activity and localization in leukocytes and platelets. AB - The plasma and serum of humans and various animal species exert an actin depolymerizing activity. Human actin-depolymerizing factor (ADF) has been purified by ammonium sulfate fractionation, DEAE-cellulose and blue-Sepharose chromatography. It is a single polypeptide of approximately 90 kDa, with a pI between 6.0 and 6.5. ADF is heat and trypsin-sensitive, inactivated by EGTA, not stained by HIO4/Schiff on sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE), and not retained on a concanavalin-A-Sepharose column. Incubation of ethanol-fixed cultured cells or unfixed cryostat tissue sections with ADF abolishes immunofluorescent actin staining, by a mechanism which involves extraction of actin from the preparations. ADF promotes fragmentation and depolymerization of actin filaments as shown by electron microscopy, differential ultracentrifugation and DNAse I inhibition assay. This depolymerized actin retains its mobility on SDS/PAGE and is able to repolymerize in the presence of EGTA. Human white blood cells and platelets (but neither human fibroblasts nor white blood cells and platelets from pig, rat and rabbit) contain a 90-kDa protein reacting with an antibody raised in rabbit against human ADF as judged by immunofluorescence and immunoblotting techniques. Immunoblots of human granulocyte subcellular fractions suggest that the protein reacting with ADF antibody is present in the soluble cytoplasmic fraction. ADF may play a role in solubilization of plasma actin and in the intracellular organization of actin, and should be useful for the evaluation of the relative stability of cytoplasmic actin filaments in various physiological and pathological processes. PMID- 2578391 TI - Biosynthesis and secretion of alpha 1 acute-phase globulin in primary cultures of rat hepatocytes. AB - Experimental inflammation in rats led to a sevenfold increase in serum levels of alpha 1 acute-phase globulin. This increase is correlated with elevated levels of translatable mRNA for alpha 1 acute-phase globulin in the liver. Biosynthesis and secretion of alpha 1 acute-phase globulin were studied in rat hepatocyte primary cultures. An intracellular form of alpha 1 acute-phase globulin with an apparent relative molecular mass of 63 500 and a secreted form of 68 000 were found. The intracellular form of alpha 1 acute-phase globulin could be deglycosylated by endoglucosaminidase H treatment indicating that its oligosaccharide chains were of the high-mannose type. The secreted form of alpha 1 acute-phase globulin was not sensitive to endoglucosaminidase H, but was susceptible to the action of sialidase reflecting carbohydrate side-chains of the complex type. Pulse-chase experiments revealed a precursor-product relationship for the high-mannose and the complex type alpha 1 acute-phase globulin. In the hepatocyte medium newly synthesized alpha 1 acute-phase globulin was detected 30 min after the pulse. Unglycosylated alpha 1 acute-phase globulin was found in the cells as well as in the medium when the transfer of oligosaccharide chains onto the polypeptide chains was blocked by tunicamycin. Tunicamycin led to a marked delay in alpha 1 acute-phase globulin secretion. PMID- 2578392 TI - Rat alpha 1-microglobulin. Purification from urine and synthesis by hepatocyte monolayers. AB - Rat alpha 1-microglobulin was isolated from the urine of rats treated with sodium chromate, and was purified by the use of gel chromatography, affinity chromatography on concanavalin-A-Sepharose and ion-exchange chromatography. The protein was heterogeneous in charge, had a tendency to form dimers, and was associated with a brown-coloured chromophore. The size of the protein (25 kDa) was similar to guinea pig alpha 1-microglobulin but smaller than the human protein, when measured with sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Immunological cross-reaction with human and guinea pig alpha 1 microglobulin was demonstrated. The concentration of alpha 1-microglobulin in rat serum was 16.4 mg/l (SD = 8.5 mg/l, n = 13) and rat serum alpha 1-microglobulin was eluted from a gel chromatography column at two different positions corresponding to monomeric alpha 1-microglobulin and IgA. The latter alpha 1 microglobulin activity could be absorbed by anti-IgA serum. Rat alpha 1 microglobulin and albumin were continuously released into the medium of rat hepatocyte monolayers, and alpha 1-microglobulin was isolated from the medium by the use of immunoprecipitation with anti-(alpha 1-microglobulin). Tritiated leucine, added to the medium, was incorporated into the protein, suggesting a de novo synthesis of alpha 1-microglobulin by the hepatocytes. The size of hepatic alpha 1-microglobulin was similar to that of purified urinary rat alpha 1 microglobulin, when determined with sodium dodecyl sulfate/polyacrylamide gel electrophoresis. PMID- 2578394 TI - Strain-dependent variation in ribosomal DNA arrangement in Absidia glauca. AB - Restriction analysis of total DNA from the zygomycete Absidia glauca reveals a pattern of prominent bands on a homogeneous background. By Southern blot analysis with 32P-end-labelled ribosomal RNA most of these bands could unequivocally be identified as repetitive copies of ribosomal DNA. There are marked differences in restriction patterns of rDNA between all seven strains tested, even of strains belonging to mating type pairs, presumably isolated from the same location. By using purified rRNAs as probes in hybridization experiments, evidence is presented that 5S rRNA is part of the ribosomal repetitive unit. A more detailed analysis of one strain pair [A. glauca CBS 100.48 (+)/101.48 (-)] provided evidence that the (+) strain, in addition to one rDNA repeat unit common to both strains, contains a second one, derived from the common form by a small deletion. PMID- 2578393 TI - Purification of RNA polymerase and transcription-termination factor Rho from Erwinia carotovora. AB - Erwinia carotovora RNA polymerase consists of the holoenzyme structure sigma 2 beta beta' sigma as found in Escherichia coli and other bacteria. E. carotovora RNA polymerase can synthesize RNA using lambda, T7 of T4 DNA as templates; however, it is two times less active on these templates and is more temperature sensitive than the E. coli enzyme. The alpha subunit of the E.. carotovora enzyme is lower in molecular mass than its E. coli counterpart. The sigma factors from E. coli and E. carotovora are similar in size and in their ability to stimulate RNA synthesis by core enzyme on DNA templates such as T7 DNA. An additional protein of 115 000 Da molecular mass, termed gamma, is found associated with E. carotovora RNA polymerase. The gamma protein is tightly associated with the polymerase subunits as it is not dissociated by gel filtration in buffer containing 0.5 M NaCl. It can be purified by passing the Agarose 1.5 m enzyme through coupled Bio-Rex 70 and DEAE-cellulose columns. The gamma-protein, when present in excess over the sigma subunit, inhibits holoenzyme activity on T7 DNA but not on poly[d(A-T)]and may thus interfere with sigma activity. The gamma protein by itself cannot transcribe T7 DNA or poly[d(A-T)], nor does it stimulate core enzyme activity on T7 DNA. E. carotovora rho has a subunit molecular mass of 48 000 Da and exhibits RNA-dependent phosphohydrolysis of adenosine ribonucleoside triphosphate. E. coli and E. carotovora rho are indistinguishable immunologically, as total fusion of precipitin bands is observed. E. carotovora rho elutes from a phosphocellulose column at a salt concentration of about 0.21 M KCl, compared to that of 0.29 M KCl for E. coli rho. The poly(C)-dependent ATPase activity of E. carotovora rho is more-temperature sensitive and is six to ten times less active than that of E. coli rho. E. carotovora rho is capable of terminating RNA transcripts, as indicated by a decrease in RNA synthesis using lambda or T7 DNA as template and E. carotovora or E. coli polymerase as the transcribing-enzyme. PMID- 2578395 TI - Quantitation of multiple sclerosis specific central nervous system antigens in various regions of MS brains. AB - We have estimated the levels of partially purified multiple sclerosis (MS) specific glycoproteins (MSG2) in gray matter, white matter, spinal cord and brain stem of MS autopsy brains by an enzyme immunoassay in which antisera to a pooled MSG2 was employed. Similarly, the levels of KG2 (non-MS brain isolate corresponding to MSG2) were assayed in various topographic areas of non-MS autopsy brains. Comparison of data on MS and non-MS groups revealed that the MS specific antigens may be preferentially located in the normal appearing white matter of MS brains. The concentration of MS antigens was found to be highest in the normal appearing white matter of MS brains, followed by periplaque and finally plaque. These results indicate that the MS specific antigens are not the degraded products of MS brains. They further support the view that normal appearing white matter of MS brains should be the target tissue for the isolation of MS specific antigens. PMID- 2578396 TI - HLA-DR-, MB- and novel DC-related determinants restrict purified protein derivative of tuberculin (PPD)-stimulated human T cell proliferation. AB - Class II major histocompatibility complex determinants restricting recognition of tuberculin antigens (purified protein derivative; PPD) were studied by using monoclonal antibodies (mAb) to block lymphoproliferative responses. Anti-class II mAb were shown to exert inhibitory effects at the level of the antigen-presenting cells, without inducing suppressive lymphocytes or macrophages. Using panels of HLA-typed antigen-presenting cells and nonalloreactive proliferative T cell lines, derived by limiting dilution, restriction elements for PPD responses appeared to correlate with the donor's HLA-DRw6 specificity (one clone), MB1 (one clone), MB3 (one clone), or no established class II (or class I) specificity (three clones). mAb TU22, reacting with nonpolymorphic DC-like determinants, strongly inhibited stimulation of all clones except that restricted by DR antigens, suggesting the DC-like character not only of the MB1- and MB3 associated, but also of the unassigned, restriction elements of these cloned lines. In contrast, stimulation of the DR-restricted line was strongly inhibited by DR/SB-specific mAb which only weakly inhibited the stimulation of clones restricted by DC-like determinants. These results suggest that clonally distributed PPD-reactive proliferative lymphocytes from a single donor may be restricted by at least three different class II determinants (HLA-DR, MB, or a second, novel, DC-related molecule). PMID- 2578398 TI - Cytotoxic T cell clone-specific monoclonal antibodies used to select clonotypic antigen-specific cytotoxic T cells. AB - Two rat monoclonal antibodies (mAb) have been produced which recognize a clone specific determinant on the alloreactive cytotoxic T lymphocyte (CTL) clone 3 F9. CTL clone 3F9 of BALB/c origin is specific for H-2Db and can be grown by weekly restimulation with irradiated stimulator spleen cells expressing H-2Db in the presence of interleukin 2. Two mAb against T cell clone 3F9, 44-22-1(IgG2a) and 46-6 B5(IgM), have been proven to be clone specific: they inhibit cytotoxic activity of 3F9 only and bind specifically to 3 F9 when compared in a panel of different CTL clones, or cells from different mixed lymphocyte cultures (MLC), BALB/c thymus and spleen cells. The mAb 44-22-1 has been used to sort cells from a primary MLC BALB/c anti-H-2Db by fluorescence-activated cell sorter (FACS) to select CTL expressing 3 F9 clonotype-specific determinants. The lymphocytes reactive with 44-22-1 represent a minor subpopulation of the CTL of the primary MLC. The specific alloreactive cytotoxicity of unsorted lymphocytes of the bulk primary MLC could not be inhibited by the mAb 44-22-1 and 46-6 B5 whereas the sorted 3 F9 clonotype-positive cultures could be inhibited very effectively. All the CTL clones derived from the FACS-sorted clonotype-positive culture show all the same properties and are identical with clone 3 F9 with respect to antigen specific cytotoxicity, inhibition of cytotoxicity by the mAb and surface markers. PMID- 2578397 TI - Analysis of immunological tolerance to major histocompatibility complex antigens. I. High frequencies of tolerogen-specific cytotoxic T lymphocyte precursors in mice neonatally tolerized to class I major histocompatibility complex antigens. AB - Injection of (CBA X A)F1 cells into neonatal CBA mice rendered them tolerant to skin grafts of (CBA X A)F1 origin. Limiting dilution analysis revealed a very low frequency of tolerogen-inducible cytotoxic T lymphocyte precursors (CTL-P) in spleens of tolerant mice. Two in vitro procedures allowed, however, the induction of tolerogen-specific CTL-P of high frequencies in tolerant mice: (a) the "by pass" activation of spleen cells from tolerant mice by concanavalin A under short term bulk culture conditions followed by culture of limiting numbers of activated responder cells, and (b) absorption of spleen cells from tolerant mice on monolayers of tolerogen-activated T cells from normal syngeneic mice. Furthermore, spleen cells from tolerant mice, recently challenged with a tolerogen-bearing skin graft, specifically suppressed the activation of tolerogen reactive splenic CTL-P from normal CBA mice under limiting dilution conditions. These data confirm the presence of tolerogen-specific CTL-P of high frequency in tolerant mice and suggest their functional inactivation through a suppressive mechanism. PMID- 2578399 TI - The murine thymic nurse cell: an isolated thymic microenvironment. AB - The thymic nurse cell (TNC) consists of an epithelial cell enclosing lymphoid elements and is found in enzymic digests of the thymus. Although these structures have been implicated in the normal intrathymic development of T lymphocytes, little is known about the in situ structure of this unusual cell complex. In this study, various dyes were introduced into the intact thymus and their differential permeability was used to demonstrate that the TNC exists as a sealed structure in situ. The lymphocytes within the TNC were shown to be isolated from the general thymic environment. Preliminary studies on these lymphocytes and the physiology of their active release from individual, micromanipulated TNC in microcultures are reported. PMID- 2578400 TI - T cell-replacing factor in specific antibody responses to influenza virus by human blood B cells. AB - In man, B cell maturation factors obtained from T cells or T cell lines have been shown to induce antibody formation in mitogen or anti-immunoglobulin activated B cells, and in some continuous B cell lines, but the relationships between these factors and B cell differentiation factors in antigen-specific antibody responses is unclear. We have now shown that supernatants from phytohemagglutinin-activated tonsil cells, or from the Gibbon Ape T cell line MLA-144, can substitute for T cells in the specific antibody response by human blood B cells to influenza virus. Thus, T cell-depleted non-rosette-forming (E-) cells prepared from peripheral blood mononuclear cells made antibody when cultured with antigen and factor together, whereas control cultures of E- cells with either antigen or factor alone did not. Moreover, E- cells cultured with factor and influenza virus strain A/X31 made antibody to A/X31, but not the non-cross-reacting strain, B/HK (and vice versa) showing that the response was antigen specific. The activity in these supernatants, therefore, fulfilled the functional definition of T cell replacing factor (TRF). The possibility that interleukin 2 (IL 2) present in the TRF-containing supernatants was expanding residual T cells in the E- preparations to provide normal T cell help was excluded in three different ways. First, E- cells depleted of T (Leu4+) cells to undetectable levels made normal amounts of antibody when cultured with antigen and TRF. Secondly, a limiting dilution technique was employed to show that help in cultures of E- cells and TRF was not mediated by antigen-specific T helper cells. Thirdly, TRF-containing supernatants depleted of IL2 retained activity, whereas purified IL2 was inactive. Preliminary purification of TRF by gel filtration on Ultrogel AcA54 columns showed that all the activity eluted in a single peak between 35 000 and 43 000 molecular weight. This distinguishes human TRF from IL 2 and from other B cell maturation factors with a molecular weight range of 15 000-20 000 which act on continuous B cell lines. In addition to TRF, supernatants from phytohemagglutinin-activated tonsils also contained a factor which could induce polyspecific IgM production, but only in cultures containing significant numbers of T cells. This additional activity may have been due to IL 2, and provides an explanation for the apparent T cell dependent effects sometimes observed in experiments designed to test B cell differentiation factors on T cell-depleted normal B cells. PMID- 2578401 TI - Investigation of early T cell activation: analysis of the effect of specific antigen, interleukin 2 and monoclonal antibodies on intracellular free calcium concentration. AB - The three mitogenic anti-T3 antibodies, UCHT1, anti-Leu-4 and WT-32, all produce a rapid increase in T cell intracellular Ca2+ ( [Ca2+]i) in all individuals, as measured by quin 2 tetra-acetoxymethyl ester fluorescence. This indicates that the lack of responsiveness of approximately 30% of individuals to UCHT1 in proliferation assays is not due to failure of the antibody to elicit Ca2+ mobilization and that a rise in [Ca2+]i is per se not adequate to induce cell division. Another mitogenic antibody, WT-31, which is directed against the constant portion of the T cell receptor, did not, however, produce a rapid calcium rise in peripheral blood T cells. The clone HA1.7 gave a similar Ca2+ response to UCHT1. WT-31 did not induce a rise in [Ca2+]i, nor did the specific antigen to which the clone responded. Accessory cells may be required to induce Ca2+ mobilization with these ligands. There was no response to IL2, or an antibody (anti-Tac) to the IL2 receptor. In contrast to peripheral blood T cells treatment of HA1.7 with WT-31 led to an enhancement of the calcium response to subsequent UCHT1 addition. Furthermore, cross-linking of WT-31 on the surface of HA1.7 cells did produce a small rise in [Ca2+]i. The IL2-independent malignant T cell line, HUT78, exhibited a calcium response to both UCHT1 and WT-32. Both of these responses occurred without cross-linking. The T cell receptor is closely associated with cell-surface proteins, including the T3 antigen and these studies confirm the importance of the T3 antigen in T cell activation. They also suggest that the relationship between the T cell receptor and the T3 antigen may vary in T cells in different proliferative states. PMID- 2578402 TI - Antigen-specific cytotoxic T cell and antigen-specific proliferating T cell clones can be induced to cytolytic activity by monoclonal antibodies against T3. AB - T3 is a human differentiation antigen expressed exclusively on mature T cells. In this study it is shown that anti-T3 monoclonal antibodies, in addition to their capacity to induce T cells to proliferate, are able to induce antigen-specific cytotoxic T lymphocyte clones to mediate antigen nonspecific cytotoxic activity. It is furthermore shown that anti-T3 reagents are able to trigger lytic activity in T cell clones characterized as noncytotoxic antigen-specific proliferating T cells. The data presented indicate that perturbation of T3 can trigger the lytic machinery in cytolytic as well as noncytolytic T cell clones. PMID- 2578403 TI - Clonal variations in keratin. Intermediate filament expression by human somatic cell hybrids. AB - The intermediate filament composition of differentiated vertebrate cells provides a stable phenotype which appears to be specifically regulated in each cell type. In order to analyse the regulation of intermediate filament expression we have constructed human somatic cell hybrids from the fusion of the HeLa-derived cell line HEB7A and a normal human diploid fibroblast, GM2291. These parental cells differ with respect to the presence or absence of keratin intermediate filaments. Isolation of independently arising clones produced two classes of hybrids. One class expresses keratin in a stable manner and the other class lacks keratin altogether. Indirect immunofluorescence of hybrid cells using antikeratin antiserum demonstrates that there are variations in the intensity and organization of cytoskeletal keratin staining. SDS-PAGE comparisons of cell extracts from these hybrids indicates that there are quantitative differences in the relative amounts of individual keratin polypeptides as well. These clonal variations have allowed us to begin assessing the consequences of genetic interactions between cell types that are normally capable of closely regulating different subsets of intermediate filament genes. PMID- 2578404 TI - Monoclonal antibodies to epitopes on different regions of the 200 000 dalton neurofilament protein. Probes for the geometry of the filament. AB - Neurofilaments in mammalian nervous tissues have three subunit proteins. These subunit proteins have apparent molecular masses of 200 (NF200), 150 (NF150) and 68 (NF68) kD. Biochemical assembly studies have indicated that the NF68 protein forms the core of the filament and that the other two proteins are associated proteins. Electron microscopy immunolocalization studies have been performed previously on isolated filaments and on filaments from neurons in culture, and have confirmed the localization of NF68 as a core filament protein and NF200 as a peripheral protein. We have raised two monoclonal antibodies to the NF200 components. Using immunogold labelled protein A, we have been able to localize these antibodies to tissue sections of adult cerebellum at the EM level. With this method, we have found that one of the monoclonal antibodies (NF2) shows a linear arrangement of gold particles directly on the filament, whereas the second monoclonal antibody (NF111) reacts with the filaments to give a periodic arrangement of gold particles. By immunoblotting against chymotryptic fragments of the NF200 protein, we have found that the mAB-NF111 reacts solely with a 160 kD piece, whereas the other monoclonal antibody reacts with both the 160 kD piece and the 40 kD piece. The latter piece was shown to be associated to the filament by binding studies with iodinated NF68. Thus the EM localization studies and the biochemical studies indicate that the two monoclonal antibodies react with different parts of the NF200 molecule, one binding to a part of the molecule which is located closer to the filament, and one to a more peripheral part of the molecule. PMID- 2578405 TI - Quantitation of metabolic cooperation by measurement of HGPRTase activity. AB - A method for the quantitation of metabolic cooperation between cells is described. The method depends upon measuring the increase in HGPRTase activity that occurs between HGPRT+ cells and the HGPRT-LN (Lesch-Nyhan) cells. The variables upon which this method depends and their effect on the final determination are discussed. PMID- 2578406 TI - Intracellular degradation of asialoglycoproteins in hepatocytes starts in a subgroup of lysosomes. AB - Isolated rat hepatocytes take up and degrade [125I]tyramine-cellobiose-labelled asialofetuin [( 125I]TC-AF). The labelled degradation products are trapped at the site of degradation. The intracellular transport of [125I]TC-AF was studied by means of cell fractionation in Nycodenz gradients. The labelled ligand was kept in a small, slowly sedimenting vesicle during the first minutes after uptake in the cells, and was then transferred to a larger endosome. Labelled degradation products first appeared in an organelle with the same density distribution as the larger endosome and then in a denser organelle. These observations suggest that two types of lysosome, 'light' lysosomes and 'dense', are sequentially involved in the degradation of the asialoglycoprotein. The bulk of the lysosomal enzymes is associated with the dense lysosome. PMID- 2578408 TI - Rat pancreatic islet cells in primary culture: occurrence of giant cells amenable to patch clamping. AB - Neonatal and adult rat pancreatic islet cells were maintained in dissociated cell culture for up to three weeks. The unexpected occurrence of giant (40-50 micron) cells was noted, some of which reacted positively to an insulin antiserum, indicating the presence of insulin. The giant cells were amenable to study using the extracellular patch clamp technique, which was used to demonstrate a population of membrane channels gating outwardly directed current in these cells. PMID- 2578407 TI - Tumor-derived angiogenesis factors from rat Walker 256 carcinoma: an experimental investigation and review. AB - Angiogenesis, the process of developing a hemovascular network, is an essential feature of the growth of solid tumors, and is induced by factors secreted by tumor cells. Assay procedures suitable for the investigation of angiogenesis, and for the screening of angiogenesis factors during purification are reviewed; and a number of reports describing the purification of angiogenesis factors, primarily from the rat Walker 256 carcinoma as starting material, are discussed. Work from the authors' laboratory is also presented. Walker 256 cells grown in large-scale culture were the source of a reproducible and homogeneous source of angiogenic material. Factors secreted by these cells were isolated by a series of chromatographic steps. Ion exchange chromatography on carboxymethyl-Sephadex produced two active fractions, one of which was fractionated into several macromolecular species by lectin affinity and hydrophobic adsorption chromatography. The other gave a high mol.wt, active fraction that was resolved into a low mol.wt, active component and a non-angiogenic but possibly carrier molecule with a mol.wt of 140,000. While none of the angiogenic factors were identified chemically, the results demonstrate the existence of both high and low mol.wt tumor-secreted angiogenic substances, confirming the hypothesis for tumor induced angiogenesis and predicting potential means to interfere with the process of tumor growth. PMID- 2578409 TI - Bicuculline and picrotoxin block gamma-aminobutyric acid-gated Cl- conductance by different mechanisms. AB - Using isolated, internally perfused bullfrog dorsal root ganglion cells we have studied the dose-response curves for gamma-aminobutyric acid (GABA) in the presence of internally or externally applied GABA antagonists. With external application of antagonists the inhibition of the GABA current by bicuculline was competitive and that by picrotoxin was noncompetitive. Picrotoxin but not bicuculline blocked when internally perfused. PMID- 2578410 TI - Serum-induced stimulation of snRNA synthesis in mouse 3T3 fibroblasts. AB - Small nuclear RNAs (snRNAs) from quiescent and serum-stimulated 3T3 cultures, labeled with [3H]uridine [( 3H]U), were electrophoresed in polyacrylamide-urea slab gels and revealed by staining with ethidium bromide and by fluorography. Judged by labeling with [3H]U, synthesis of 7S and U1-U6 RNAs was very low or absent in quiescent cultures. The serum-induced transition of 3T3 cells from a resting to a growing state was accompanied by an early, apparently sequential stimulation of snRNA synthesis; stimulated synthesis of 7S, U1, U2, U3, U4 and U6 RNAs coincided in time with serum-induced stimulation of 45S pre-ribosomal RNA (pre-rRNA) and heterogeneous nuclear RNA (hnRNA) synthesis. PMID- 2578411 TI - Hydrodynamic studies of a DNA-protein complex. Elongation of single stranded nucleic acids upon complexation with the gene 32 protein of phage T4 deduced from electric field-induced birefringence experiments. AB - Short DNA and RNA fragments complexed with the helix destabilizing protein of bacteriophage T4, GP32, have been studied in solution by electric birefringence and circular dichroism. The birefringence of the complexes is positive and the magnitude indicates that the DNA and RNA fragments become linear and rigid upon protein binding. The field free decay is biphasic. On the basis of a rigid rod approximation the slow relaxation time leads to a base-base distance along the helix axis in the complex from 4.3 to 5.6 A, an elongation of at least 50% compared to single-stranded DNA. PMID- 2578413 TI - The effect of bilayer order and fluidity on detergent-induced liposome fusion. AB - Surfactants induce fusion (or increase in size) of sonicated liposomes. This phenomenon is enhanced by cholesterol and inhibited by the intrinsic polypeptide gramicidin A. By comparison with previous physical studies we conclude that liposome 'fusion' is facilitated when both fluidity and static order of the bilayer are high. PMID- 2578412 TI - Elucidation of cathepsin B-like activity associated with extracts of human myelin basic protein. AB - Myelin basic protein (MBP) extracted from human delipidated white matter was found to be degraded at pH 3.0 by endogenous proteolytic activities of extracts. Electrophoretic peptide patterns were consistent with limited proteolysis of MBP. Based on pH, activation by EDTA and DTE, and inhibition by p-CMPS, E-64 and, in particular, by leupeptin, the protease involved was tentatively identified as cathepsin B or a cathepsin B-like enzyme. As pepstatin failed to inhibit acid proteolysis of MBP cathepsin D was ruled out. PMID- 2578414 TI - Phorbol ester (TPA) potentiates noradrenaline and acetylcholine-evoked amylase secretion in the rat pancreas. AB - The effect of the phorbol ester 12-O-tetradeconyl-phorbol-13-acetate (TPA) on noradrenaline (NA) and acetylcholine (ACh)-evoked amylase secretion in isolated segments of rat pancreas was investigated. TPA alone evoked a relatively small increase in amylase output. However, when combined with either noradrenaline or ACh, the phorbol ester markedly enhanced the secretagogue-induced amylase secretion. These effects were dose related. TPA also enhanced the amylase secretion evoked by either the Ca2+ ionophore A23187 or dibutyryl cyclic AMP. This potentiation by TPA of noradrenaline, ACh, Ca2+ ionophore A23187 and dibutyryl cyclic AMP-evoked amylase output may suggest the existence of a third pathway controlling enzyme secretion in the pancreas. PMID- 2578416 TI - Reactivity in human cerebral artery: species variation. AB - It is becoming obvious that the reactivity of vascular smooth muscle to vasoactive agents is not homogeneous in different arteries (cerebral vs. other arteries) from the same animal species or in cerebral arteries from different species. In this communication, the reactivity of human cerebral arteries to norepinephrine (NE), dopamine (DA), small amounts of K+ and ouabain and their mechanisms of action are compared with those in monkey and dog cerebral arteries. NE produces moderate contractions in the primate arteries, mediated by alpha 1 adrenoceptors, and slight contractions in the dog arteries, possibly mediated by alpha 2 receptors. DA relaxes human and monkey cerebral arteries but contracts the dog arteries. The primate artery relaxation mediated by dopaminergic receptors is large enough to predominate over the alpha 1 receptor-mediated contraction. Minute amounts of K+ preferentially relax cerebral arteries from humans, monkeys, and dogs, possibly activating the electrogenic Na+ pump. Ouabain, a Na+ pump inhibitor, contracts these cerebral arteries with low concentrations. Human and monkey cerebral arteries respond similarly to vasoactive agents presented so far, and appear to share the same mechanisms of action; however, the responsiveness of dog cerebral arteries differs. PMID- 2578415 TI - A complete regulatory loop between the immune and neuroendocrine systems. AB - Infection of lymphocytes with Newcastle disease virus induces the cells to synthesize immunoreactive (ir) adrenocorticotropin (ACTH) and endorphins. The irACTH is synthesized de novo, and common properties of lymphocyte and pituitary ACTH include: antigenicity, bioactivity, molecular weight, and retention time on reverse phase high-pressure liquid chromatography. The irACTH appears to be active in vivo because a rise in serum corticosterone levels in hypophysectomized mice corresponds with spleen cell production of irACTH. Furthermore, preliminary experiments showed that B cell depletion blocked the normal rise in serum corticosterone levels after herpes simplex virus infection of intact mice. It seems that a similar system operates in vivo in humans. Typhoid vaccine, which induces lymphocyte-derived irACTH production in vitro, caused a time-dependent increase in the number of irACTH-positive lymphocytes in both hypopituitarism and normal short children. A rise in serum cortisol levels was seen in one patient with hypopituitarism and all normal patients. The above regulatory circuit also seems able to act in the reverse direction. Pituitary ACTH and alpha-endorphin can behave like lymphokines by being immunosuppressive at 0.5 microM in an in vitro antibody synthesis system. Further, lymphocytes were shown to have high affinity receptors for both of these hormones. Thus, it appears that the immune and neuroendocrine systems have the ability to signal each other through common or related peptide hormones and receptors. PMID- 2578417 TI - Production and characterization of monoclonal antibodies directed against connective tissue proteoglycans. AB - Monoclonal antibodies have been raised against determinants present in cartilage proteoglycan. Characterization of the specificity of these antibodies indicated that they recognize determinants present in the keratan sulfate glycosaminoglycan chain and on chondroitin sulfate oligosaccharide stubs attached to the proteoglycan core protein after chondroitinase digestion of the proteoglycan (i.e., delta-unsaturated 4- and 6-sulfated and unsulfated chondroitin sulfate on the proteoglycan core). The antibody recognizing keratan sulfate has been used to demonstrate the presence of a keratan sulfate-rich proteoglycan subpopulation that increases with increasing age of animal compared with chondroitin sulfate rich proteoglycans. Monoclonal antibodies recognizing determinants on chondroitinase-treated proteoglycan have been used in immunohistochemical localization studies determining the differential distribution of 4- and 6 sulfated and unsulfated proteoglycans in tissue sections of cartilage and other noncartilaginous tissues. Digestion with chondroitinase ABC or ACII can be used to differentiate between chondroitin sulfate and dermatan sulfate proteoglycan in different connective tissues. In addition, the presence of a 6-sulfated chondroitin sulfate proteoglycan that is associated with membranes surrounding nerve and muscle fiber bundles is described. Monoclonal antibodies were also raised against the link protein(s) of cartilage proteoglycan aggregate. They have been used in peptide map analyses of link protein and in demonstrating the presence of a high-mannose oligosaccharide chain of the link proteins. The presence of high-mannose oligosaccharide structures on the link protein(s) accounts for the microheterogeneity of the link proteins (link proteins 1, 2, or 3) that is observed on sodium dodecyl sulfate-polyacrylamide gels. PMID- 2578418 TI - Perifusion of a clonal cell line of Simian virus 40-transformed beta cells. Insulin secretory dynamics in response to glucose, 3-isobutyl-1-methylxanthine, and potassium. AB - A perifusion system for the study of insulin secretory dynamics of a clonal, Simian virus 40-transformed hamster pancreatic beta cell line (HIT cells) is described. After a change from glucose-free to higher glucose levels in the perifusate, insulin secretion increased rapidly in a dose-dependent manner. The pattern of glucose-stimulated insulin release was monophasic and was not sustained during a continued glucose stimulus. Perifusing the cells with low glucose (0.3 mg/ml) before a glucose stimulus of 3.5 mg/ml resulted in more rapid insulin release with lower peak secretory rates than those seen after a glucose free period. The combined stimulus of high glucose and 100 microM 3-isobutyl-1 methylxanthine (IBMX), a phosphodiesterase inhibitor, significantly enhanced the acute insulin secretory response and also resulted in a biphasic secretory pattern that was sustained throughout the 60-min stimulation period. Insulin secretion stimulated by IBMX required a nonstimulatory level of glucose in the perifusing media, and, if this requirement was met, the immediate release of insulin was similar to that evoked by high glucose alone. High potassium (40 mM) also triggered a monophasic release of insulin. These studies demonstrate that glucose or high K+, which depolarizes the plasma membrane, and IBMX, an agent presumed to increase intracellular cyclic AMP levels, can signal the acute release of insulin from these beta cells. This cell line is a unique model system for studying the mechanism of insulin secretion. PMID- 2578419 TI - Galanin inhibits insulin secretion and induces hyperglycemia in dogs. AB - Intravenous administration of galanin into fasted conscious dogs produced a dose dependent hyperglycemia accompanied by decreases in plasma insulin levels, but with no elevation of plasma glucagon levels. Galanin infusions produced greater parenteral glucose-induced rises in plasma glucose levels along with markedly blunted insulin responses compared with glucose and insulin responses to control glucose infusions. Immediately after cessation of the galanin infusions, elevation of plasma insulin levels occurred in the basal state and after parenteral glucose loading. These results suggest that galanin's hyperglycemic activity is predominantly mediated by a reversible inhibition of insulin secretion. PMID- 2578420 TI - Gastric endocrine cell hyperplasia and carcinoid tumors in pernicious anemia. AB - Endoscopic screening in 123 patients with pernicious anemia (PA) yielded 4 patients with solitary and 1 patient with multiple gastric carcinoid tumors. Quantitative histologic studies of multiple standardized biopsy specimens showed a significantly increased number of fundic mucosal argyrophil endocrine cells in 40 patients with PA when compared with 15 patients with simple fundic atrophic gastritis (p = 0.002) or 8 normal controls (p = 0.0001). Patients with simple atrophic gastritis had increased numbers of fundic mucosal argyrophil cells as compared with normal controls (p = 0.02). A significant difference was also noticed in the number of antral mucosal argyrophil cells between patients with PA and normal controls (p = 0.01), but not between patients with PA and patients with simple atrophic gastritis. It is concluded that, in addition to having hyperplasia of gastric mucosal argyrophil endocrine cells, patients with PA run an increased risk of developing gastric argyrophil cell carcinoid tumors, which should be regarded as potentially malignant. PMID- 2578421 TI - Comparative efficacy of adenine arabinoside 5' monophosphate and prednisone withdrawal followed by adenine arabinoside 5' monophosphate in the treatment of chronic active hepatitis type B. AB - Thirty-eight patients with chronic active hepatitis type B received antiviral therapy. In one trial, 22 patients were randomized to either no treatment or treatment with a 28-day cycle of adenine arabinoside 5' monophosphate (ARA-AMP); in a second trial, 13 patients were randomized to no treatment or treatment with two 28-day cycles of ARA-AMP separated by a 4-wk rest interval; during a third trial, 11 individuals were treated with 8 wk of prednisone therapy followed by 28 days of ARA-AMP therapy. The response rate (73%) to the regimen with prednisone was significantly greater than that achieved in the first or second trial (0% and 15%, respectively). The data indicate that the combination of short-term prednisone and ARA-AMP therapy may offer more promise for successful treatment of chronic active hepatitis type B than does ARA-AMP alone. Synergism may possibly occur by the combined effects of immune rebound provided by corticosteroid withdrawal and the inhibition of viral proliferation by ARA-AMP. PMID- 2578422 TI - Detection of gall stones after acute pancreatitis. AB - Four methods of gall stone diagnosis after an attack of acute pancreatitis are analysed. Of 128 consecutive patients with acute pancreatitis, 99 patients were discharged from hospital without a definite aetiology. These patients had biochemical tests performed on admission and ultrasonography and oral cholecystography performed six weeks later. The sensitivity for ultrasonography was 87% and the specificity was 93%; the respective figures for oral cholecystography were 83% and 90%. The predictive value of positive ultrasonography was 100% and of negative ultrasonography 75%; the respective values for oral cholecystography were 95% and 68%. A combination of ultrasonography and oral cholecystography failed to detect nine of 70 patients with gall stones (13%). Of 35 patients with normal ultrasonography and oral cholecystography, 33 patients had an endoscopic retrograde cholangiogram (ERCP) which showed gall stones in a further seven patients. All three methods failed to reveal gall stones in two patients, confirmed by laparotomy. The sensitivity of admission biochemical analysis was 73% and the specificity was 94%; the predictive value of a positive result was 97% and of a negative result was 57%. Biochemical analysis predicted gall stones in six of the seven patients shown by ERCP. Only 9% of patients were finally considered to be idiopathic. In conclusion ultrasonography is the investigation of choice and ERCP should be undertaken in all patients who have normal ultrasonography and/or oral cholecystography but have biochemical criteria indicative of gall stones. PMID- 2578425 TI - Impaired insulin-induced RNA synthesis secondary to a genetically defective insulin receptor. AB - The stimulation of glucose uptake and RNA synthesis by insulin was studied in cultured fibroblasts from patients with an inherited affinity defect of the insulin receptor. Additional cell cultures were set up of two patients with Alstrom syndrome, a genetic disease with insulin resistance but normal insulin receptor, and of eight healthy individuals. In receptor-defective patients we found a corresponding defect of the insulin-mediated stimulation of RNA synthesis but a normal stimulation of glucose uptake. We conclude that both postreceptor effects are controlled by different insulin-directed mechanisms. PMID- 2578424 TI - The prophase stages in human foetal oocytes studied by light and electron microscopy. AB - The progression of the prophase stages of meiosis in human foetal ovaries is reported from a series of aborted foetuses spanning the first two trimesters of gestation. A surface-spreading technique allowed cells to be examined at both light and electron microscope levels. The pachytene stage was specifically examined for evidence of synaptic or other abnormalities. Two observations of interest are the relatively high incidence with which errors of pairing occur and second the state of thickening observed when such unpaired axes are stained with silver. PMID- 2578426 TI - High resolution R banding in amniotic fluid cells using the BrdU-Hoechst 33258 Giemsa (RBG) technique. AB - While standard Giemsa banding is generally adequate for amniotic fluid chromosome analysis, small deletions, duplications, or translocation breakpoints involving G negative bands may be difficult to appreciate. We report a method for producing high resolution R banding in human amniotic fluid cultures using the BrdU-Hoechst 33258-Giemsa (RBG) technique. RBG banding can be useful in confirming and precisely defining structural abnormalities in amniotic fluid cultures. PMID- 2578427 TI - Establishment of hybridomas secreting monoclonal antibodies against C epsilon 2 and C epsilon 4 domains of human IgE. AB - Three kinds of hybridomas secreting monoclonal antibodies (MAbs) against the epsilon chain of human IgE were constructed by somatic cell hybridization between mouse myeloma P3U1 cells and spleen cells from BALB/c mice immunized with human IgE purified from the culture supernatant of U-266 cells. These MAbs were used effectively for the purification and determination of human IgE. The recognition site in the IgE molecule of each antibody was examined by using various epsilon chain fragment peptides produced in Escherichia coli. From these experiments, it was suggested that one recognized C epsilon 2 and the second C epsilon 4. The third did not recognize the C epsilon 1-C epsilon 4 domains of the recombinant epsilon chain from E. coli, although it bound to the epsilon chain of natural human IgE. PMID- 2578423 TI - Maternal serum alpha-fetoprotein screening for neural tube defects. Report of a combined study in Germany and short overview on screening in populations with low birth prevalence of neural tube defects. AB - The basis of maternal serum alpha-fetoprotein (AFP)-screening for neural tube defects is discussed. A report is given of a large scale screening study in the Federal Republic of Germany combining the experiences in Giessen and Hannover on over 50,000 pregnant women, about evenly distributed among both centers. Published and known forthcoming data from other low incidence populations, particularly of European countries, are reviewed briefly. The conclusion is reached that general screening could effectively be instituted and in the final result should also be cost-beneficial. PMID- 2578429 TI - Reversibility of lymphokine-induced NK-like activity in virus-specific cytotoxic T-lymphocyte clones. AB - A limiting dilution microculture system, supplemented with a source of interleukin-2 (IL-2), was employed to evaluate the frequency of Moloney-murine leukaemia/sarcoma virus (M-MuLV/M-MSV)-specific cytotoxic T-lymphocyte precursors (CTL-p) which also exhibited NK-like activity. Spleen cells, obtained from M MuLV/M-MSV regressor mice, were restimulated in bulk secondary mixed leucocyte tumour cell cultures (MLTC), and subsequently plated in a culture medium supplemented with two different supernatants (SN) produced following PMA stimulation of the same EL-4 thymoma cell line. SN 20, obtained from the cell line maintained in vitro, contained IL-2 and only negligible amounts (less than 3 U/ml) of interferon (IFN), while SN 19, obtained after passage of the ascitic form of EL-4 thymoma in syngeneic mice, contained both IL-2 and IFN in high titres. The frequency of CTL-p specific for MBL-2 lymphoma cells was high and comparable in cultures supplemented with both SN (1/2 X 84 cells and 1/2 X 40 cells, respectively), while the frequency of CTL-p directed against NK susceptible YAC-1 target cells was low in SN 20 (1/90 cells) and high in SN 19 (1/5 X 40 cells). An analysis of individual microcultures established at low cell dose (1 cell/well) indicated that specific and NK-like activity could be ascribed to the same precursor cells. Furthermore, using different long-term CTL clones, we observed that, after passage in SN 20, double-reactive clones gradually lose the capacity to lyse NK-susceptible targets, while most of MBL-2 specific clones acquired NK-like activity following a few passages in SN 19. Therefore, the induction of NK-like activity is reversible and may be modulated by soluble factors present in supernatant in which CTL clones are maintained. Double reactive clones were unable to lyse NK-resistant allogeneic tumour cells or normal syngeneic blast cells. A few clones cross-reacting with H-2d alloantigens also exhibited NK-like activity when maintained in SN 19. The different pattern of CTL clone activity was associated with a morphological change in the clones themselves: the acquisition of double activity was accompanied by an increase in cell size and the appearance of numerous cytoplasmic granules. All CTL clones were phenotypically Thy-1+ and Lyt-2+ on indirect immunofluorescence and complement-dependent cytotoxicity investigation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2578428 TI - Specificity of the passive antibody-induced suppression of the humoral immune response of mice to surface antigens on human cells. AB - The effect of passively administered antibody on the humoral immune response of BALB/c mice to antigenic determinants on human cells has been examined. Antiserum raised by immunizing mice with the human leukaemic cell line K562, which lacks HLA-A,B,C antigens, was administered to mice, together with the HLA-A,B,C positive cell line, BALM-1. The antibody response to the unique antigen was assessed by measuring the ability of the resultant antiserum to inhibit the binding to BALM-1 cells of a labelled monoclonal antibody, 7B6, which is specific for a monomorphic HLA-A,B,C determinant. As an indication of the immune response to antigens common to K562 and BALM-1, the ability of the same antiserum to inhibit the binding of monoclonal antibody 6B1, which detects an epitope common to both cell lines, was measured. Passive antibody to K562 blocked the immune response of mice to the common antigen on BALM-1 cells. However, the response to the antigen not recognized by the passive antibody was unaffected, even though the two antigens were present on the same immunizing cell. Thus, the effect of passive antibody was 'determinant specific'. Similar results were obtained, irrespective of whether the i.v. or i.p. route of immunization was used, and whether the passive antibody was adsorbed onto the immunizing cells prior to injection, or administered separately. The blocking of the immune response did not depend on simple masking of the antigenic determinants by the passive antibody, since non-saturating amounts of antibody were effective. In addition, blocking activity was dependent on antibody class and on an intact Fc region. The latter considerations also imply that the outcome of passive antibody administration in this system was determined by factors other than the ability of the antigen-antibody complexes to interact directly with B cells, and indicate the importance of antigen processing and/or a mechanism such as antigen-reactive cell opsonization. PMID- 2578430 TI - Isolation of specific antigen-reactive T-cell clones from nude (nu/nu) mice infected with Mesocestoides corti. AB - Infection of nude mice with Mesocestoides corti results in spleen enlargement, with a decrease in percentage positive, but overall increase in Thy-1 positive cells. A low frequency of both parasite antigen-specific and alloantigen-reactive T-cell clones were isolated from the spleen, mesenteric lymph nodes, peritoneal exudate and Peyer's patches. The T-cell clones from spleen were found to express the antigens Thy-1, Lyt-1 and Lyt-2; furthermore, after stimulation with antigen in the absence of exogenous T cell growth factor (IL-2), they produced normal levels of haemopoietic growth factor (IL-3), bone marrow proliferation activity and eosinophil differentiation activity. A higher proportion produced IL-2 compared to clones from normal mice. The isolation of antigen-specific T-cell clones showing normal T-cell characteristics from young nude mice adds weight to suggestions that exposure to antigen results in significant extra-thymic T-cell maturation. PMID- 2578432 TI - Suppression of lymphoproliferation by hapten-specific suppressor T lymphocytes from mice exposed to ultraviolet radiation. AB - Application of a contact-sensitizing agent to the skin of mice previously exposed to UV radiation at a different site results in the induction of hapten-specific suppressor T lymphocytes. When splenic lymphocytes from such mice were cultured with normal lymphocytes and hapten-conjugated splenic adherent cells, the primary proliferative response was suppressed. The cell responsible for the suppression in vitro was a T lymphocyte, and two signals were required for its induction, ultraviolet radiation and hapten sensitization. The T cell suppressing lymphoproliferation was specific for the hapten applied after UV radiation. The UV-induced T suppressor cell inhibited only primary lymphoproliferation; the response of lymphocytes from immunized mice was unaffected. The activity of the UV-induced suppressor cell was not affected by mitomycin C treatment. Thus, suppression of the primary proliferative response of lymphocytes to hapten modified syngeneic cells in vitro correlates with in vivo suppression of contact hypersensitivity by these UV-induced suppressor cells. This suggests that the suppressor cells act by preventing the proliferation of hapten-specific responder clones. Use of this in vitro assay system should facilitate investigation of the characteristics of these cells and the mechanism by which these regulatory T lymphocytes inhibit contact sensitization. PMID- 2578431 TI - Enhancement of immunity against RSV-induced sarcomas by generation of hapten reactive helper T lymphocytes. AB - Previous work from this laboratory has shown that preimmunization of syngeneic hosts with Rous sarcoma virus (RSV)-transformed cells elicits a strong immune response against the growth of transplantable RSV sarcomas, mediated by T lymphocytes expressing the surface phenotype of helper cell precursors (Prat, Di Renzo & Comoglio, 1983). This paper shows that anti-tumour immunity may be elicited in tumour-bearing animals by triggering an experimentally pre-amplified T-helper cell population at the site of tumour growth. Mice were treated with cyclophosphamide (which inactivates suppressor T cells) followed by skin sensitization to trinitrochlorobenzene (TNCB) according to a protocol that has been shown to induce an appreciably amplified generation of trinitrophenyl (TNP) reactive helper T cells (Fujiwara et al., 1984). Five weeks after TNCB painting, mice were transplanted s.c. with a lethal dose of RSV-induced syngeneic sarcoma cells; the injection at the tumour site of TNCB induced the regression of the tumour in mice in which the TNP-helper cell population has been amplified, but not in controls, including those injected with a non-related hapten or sensitized to TNCB without inactivation of suppressors. PMID- 2578433 TI - Effect of liposomal amphotericin B on murine macrophages and lymphocytes. AB - The effect of liposome-encapsulated amphotericin B on mouse macrophages and on T- and B-lymphocyte functions in vitro was compared with that of free amphotericin B. Liposomal amphotericin B was generally less toxic than the free form of the drug. Low concentrations of free amphotericin B completely inhibited the serum dependent induction of transglutaminase, a marker for macrophage differentiation, and production of superoxide anion by macrophages, whereas encapsulation of the drug within liposomes protected the cells from these adverse effects. Liposomal amphotericin B did not affect the blastogenic response of T cells compared with the free drug, which was inhibitory at high concentrations. Antibody production in vivo was inhibited partially by both free and liposomal amphotericin B. These results thus suggest that encapsulation of amphotericin B in liposomes reduces the immunosuppressive effects exerted by free amphotericin B. This provides further justification for therapeutic use of liposomal amphotericin B in systemic fungal infections (G. Lopez-Berestein, R. Mehta, R. L. Hopfer, K. Mills, L. Kasi, K. Mehta, V. Fainstein, M. Luna, E. M. Hersh, and R. L. Juliano, J. Infect. Dis. 147:939-945, 1983). PMID- 2578434 TI - Relation of capsular materials and colony opacity to virulence of Vibrio vulnificus. AB - Colonies which varied in opacity were isolated from the four strains of Vibrio vulnificus. Opaque and translucent colonial types of the strains were distinguished from the corresponding parent strains. Variation in the opacity of colonies formed by each strain was accompanied by variation of capsular material formation, which was clarified by electron microscopy of the organisms stained with ruthenium red. The opaque-type colonies of the strains had capsular materials. On the other hand, three translucent-type colonies had no observable capsular materials, and one had incomplete capsular materials, in contrast to the corresponding opaque type. The corresponding opaque and translucent types of the strains were compared for points of virulence in mice and guinea pigs. By having capsular materials, the bacterial strains acquired resistance to serum bactericidal action, antiphagocytic activity, high lethality for mice, and strong invasiveness in the subcutaneous tissue of guinea pigs. Capsular materials of V. vulnificus were considered to be important for the expression of virulence. PMID- 2578435 TI - Immune response to a thymus-independent antigen (DNP-Ficoll) in the guinea pig. AB - Guinea pigs immunized with DNP30-Ficoll produced IgM antibody only. No IgG1, IgG2, IgE antibodies or delayed hypersensitivity were detected in these animals. However, Arthus reactions, induced by the hapten coupled to a foreign carrier or the whole antigen, were found. The time course of the IgM response was limited and the response to reinjection of the antigen reduced. Cyclophosphamide (CY), given 3 days before primary immunization, prolonged the IgM response. Given on the day of immunization or 3 days after CY reduced this response. CY given on days +3 or +7 after primary immunization completely suppressed the response to antigen reinjected 42 days later. Arthus reactions were totally suppressed by CY given on the day of immunization, or 3 or 7 days later. PMID- 2578436 TI - Three epitope-specific monoclonal antibodies against the hapten penicillin. AB - Three monoclonal antibodies (Pen 4, Pen 7 and Pen 9) were raised against the benzylpenicilloyl group and used to investigate the antigenicity of this group. The binding of Pen 4 to carrier-bound penicillin derivatives was shown in an ELISA to be dependent on the structure of the side chain in the derivative. Hence Pen 4 recognizes this side chain. From the difference in binding to carrier-bound penicillin derivatives in a competitive enzyme immunoassay it was concluded that Pen 7 mainly recognizes the new antigenic determinant which emerges from the binding of the penicillin derivative to a carrier. The binding of Pen 9 to carrier-bound penicillin derivatives was not influenced by the nature of the side chain. Neither was the bound or free nature of the derivative of influence on the binding. Therefore it is concluded that Pen 9 mainly recognizes the thiazolidine ring of penicillin. This study thus shows that in the benzylpenicilloyl group at least three epitopes can be recognized. PMID- 2578437 TI - Inhibition of rat peritoneal mast cell histamine secretion by protoporphyrin and incandescent light. AB - Rat peritoneal mast cells (RPMC) exposed to protoporphyrin (PP) and incandescent light (IL) become refractory to the stimulatory effects of compound 48/80. Once initiated, this refractory state continues to develop even after removal of the light source and is essentially complete within 30 min. While this state of unresponsiveness appears to be relatively permanent in the dark, prolonged incubation in the light (greater than 80 min) induces cell lysis. We have shown that the resistant state is not specific for the mast cell stimulator compound 48/80. Mast cells passively sensitized with IgE and illuminated for 30 min in the presence of 100 ng/ml PP also fail to release histamine upon stimulation by anti rat IgE, anti-rat F(ab')2, concanavalin-A (Con-A), and the calcium ionophore A23187. The inability to respond to immunological stimuli could not be ascribed to the reversible loss of membrane-bound IgE from its receptor. While the binding of either the inducer to IgE or IgE to its receptor may actually be impaired in refractory cells, the significance of such impairments on the development of the resistant state in these cells is precluded by the inability of A23187 to either increase intracellular 45Ca2+ levels or induce histamine release. The data suggest that the RPMC refractory state develops as a result of covalent inter- and/or intramolecular cross-linking of membrane proteins. Furthermore, this cross linking may involve sulfhydryl or amino groups essential to either stimulus transduction, or the histamine secretory process itself. PMID- 2578438 TI - Standardization of allergenic extracts of Aspergillus fumigatus. Liberation of IgE-binding components during cultivation. AB - During cultivation of Aspergillus fumigatus a rapid liberation of IgE-binding components was found reaching maximum values during the logarithmic phase of growth (phase I). After a fall in IgE-binding titers during phase II, appearance of additional IgE-binding components was noted during the period of lysis of the microorganism (phase III). These latter allergenic components are different from the phase I IgE-binding components, as was shown by crossed-inhibition studies. The number of precipitating antigenic components was not related with the corresponding IgE-binding titers and showed an increase during all phases of growth. The rapid changes in both IgE- and IgG-binding properties and the discrepancies between precipitating properties and IgE binding are discussed in relation to standardization and quality control of aspergillus extracts. PMID- 2578439 TI - Murine monoclonal antibody LAM2 defines cell membrane determinant with preferential expression on human lung small-cell carcinoma and squamous-cell carcinomas. AB - Murine monoclonal antibodies (MAbs) were generated against a human undifferentiated lung carcinoma cell line. The hybridoma designated LAM2 produced an IgM kappa MAb with reactivity to the cell membrane. Indirect immunofluorescence staining and radioimmunoassay showed LAM2 antibody to react preferentially with lung small-cell carcinoma (SCC) cell lines and squamous-cell carcinoma (SQC) cell lines. LAM2 antibody also stained primary cultures of normal bronchial epithelial cells, but was unreactive with human erythrocytes and nucleated marrow cells. Indirect immunofluorescent staining with LAM2 antibody was performed on frozen sections of human tumor tissues and normal tissues. LAM2 antibody stained all 8 SCC carcinomas, 4 of 5 SQC of the lung and head and neck region, and 2 or 4 lung large-cell carcinomas. No staining was seen on lung adenocarcinomas, breast carcinomas, ovarian carcinomas, renal cell carcinomas, colon carcinomas, or mesotheliomas. Staining was present on sections of normal bronchus, but not on normal lung parenchyma, liver, kidney, adrenal or skin. While LAM2 antibody was highly reactive with all SCC examined, its antigenic determinant was not expressed in other cell lines and tumors of presumed neuroectodermal origin, including neuroblastoma, melanoma, and bronchial carcinoid. Radioimmunoprecipitation showed the antigen defined by LAM2 antibody to have two major bands of approximate molecular weights of 45,000 and 125,000. The selective reactivity of LAM2 antibody with SCC and SQC, but not with most other tumor tissues and normal tissues, makes it a good candidate for use in clinical diagnosis and possibly serotherapy. PMID- 2578440 TI - AFP-synthesis induction in mouse hepatomas. AB - Highly differentiated, spontaneous hepatomas occurring in 13- to 15-month-old CBA mice were unable to produce embryo-specific serum protein alpha-fetoprotein (AFP). AFP synthesis, however, was induced in such tumors by minimal mechanical damage (small incisions of the tumors). On the 3rd day following surgery, AFP positive cells were detected in two zones: (1) along the inflammatory shaft arising around the peripheral parts of incisions, and (2) near large blood vessels draining the damaged areas. It is suggested that mechanisms regulating AFP synthesis in highly differentiated hepatomas are similar to those of the normal liver and are related to local structural rearrangements. PMID- 2578442 TI - Induction of the expression of HLA class I antigens on K562 by interferons and sodium butyrate. AB - Using sodium butyrate and alpha, beta, and gamma interferons as inducing agents it has been possible to demonstrate the triggering of HLA class I antigen synthesis in the K562 cell line. This cell line, widely used to study hemopoietic differentiation, does not naturally express HLA antigens. This effect was confirmed by the detection of HLA class I antigens on the cell membrane with specific monoclonal antibodies, by immuneprecipitation, and by isolation of specific HLA ABC messenger RNA, in the induced cells. No synthesis of HLA class II antigens was observed. Because leukemic cells can be considered as a model representing certain stages of normal hemopoietic differentiation, the expression of HLA antigens on K562 cells induced to differentiate could be interpreted as an event related to the process of differentiation itself. The lack of expression of DR antigens may result from a genetic defect as observed for beta 2-microglobin in Daudi cells. PMID- 2578441 TI - HTLV-positive and -negative T-cell lymphomas. Morphological and immunohistochemical differences between European and HTLV-positive Japanese T cell lymphomas. AB - A total of 56 cases of malignant lymphoma presumed to be of peripheral T-cell origin were investigated with regard to histological and immunohistochemical features. The goal of the study was to determine whether virus-associated T-cell lymphomas can be morphologically or immunohistochemically distinguished from presumably virus-negative T-cell lymphomas. The cases came from endemic and non endemic regions of Japan, the United Kingdom (including 4 Caribbean cases) and the Federal Republic of Germany. Sera of all Japanese and Caribbean patients and 8 German patients were tested for antibodies to adult T-cell leukaemia virus associated antigen HTLV-A. In all cases sections were examined blind by 5 well trained histopathologists. In most cases cryostat sections could be prepared from fresh tissue specimens and stained with a large panel of monoclonal antibodies. All HTLV-A-positive cases were morphologically classifiable as the pleomorphic type of T-cell lymphoma. Approximately 70% of the tested cases of pleomorphic T cell lymphoma, however, showed a positive serum reaction for HTLV-A. All other types of peripheral T-cell lymphoma (T-immunoblastic lymphoma, chronic lymphocytic leukaemia of T type, T-zone lymphoma, "AILD type" and lymphoepithelioid cell lymphoma) were HTLV-A-negative and mostly observed in European patients. Thus virus-associated T-cell lymphomas appear to be invariably of the pleomorphic type; but pleomorphism is not specific to HTLV-A-positive cases. This was also evident from the results of an experiment in which 2 Japanese histopathologists attempted to recognize HTLV-A positivity in a blind study of pleomorphic T-cell lymphomas. A maximum of about 80% of cases were correctly identified, with about 10% false-positive diagnoses (in HTLV-A-negative or presumably negative cases) and 10% false-negative diagnoses. The immunohistochemical analysis revealed not only many common features but also 2 distinct differences between HTLV-A-positive and -negative T-cell lymphomas. All but one of the HTLV-A-positive cases showed reactivity with anti-Tac and all cases in the virus-positive group were negative for TU14. All other cases were Tac-negative and approximately 65% of these cases exhibited reactivity with TU14. Preliminary cytogenetic observations suggest that there are also differences in specific chromosome aberrations. PMID- 2578443 TI - The major histocompatibility complex of the cynomolgus monkey: absorption analysis of 24 CyLA antisera. AB - The major histocompatibility complex (MHC) of the cynomolgus monkey consists of at least 35 serologically defined specificities, 14 of which have been assigned to the CyLA-A locus, 10 to the B locus, and six to the newly identified C locus. Selected specificities and antisera were further studied by the analysis of data obtained from absorptions with single donor platelets of known CyLA type. These data confirmed the existence of four groups of cross-reactive specificities identified by serological typing and revealed that three other well-defined specificities could be divided into two or more subtypes. Seven sera were shown to contain two or more populations of distinct, probably noncross-reactive antibodies that could be readily separated by absorption. Of the 24 sera analyzed, only three could be considered likely to contain antibodies reactive with a single CyLA specificity. At least three antibody specificities, after repeated absorption attempts, could not be readily removed by platelets and may reflect poor expression of the determinants on the platelet membrane. The complexity and degree of polymorphism of the CyLA system approaches that known for the human HLA complex. This homology of genetic organization and serologic features provide additional evidence in yet another species for the important role that these systems of alloantigens play in the organism. PMID- 2578444 TI - High surface tension pulmonary edema induced by detergent aerosol. AB - The effect of the detergent dioctyl sodium sulfosuccinate on pulmonary extravascular water volume (PEWV) was studied in adult anesthetized mongrel dogs. The detergent was dissolved as a 1% solution in a vehicle of equal volumes of 95% ethanol and normal saline and administered by ultrasonic nebulizer attached to the inspiratory tubing of a piston ventilator. Two hours following detergent aerosol PEWV measured gravimetrically was increased compared with either animals receiving no aerosol or those receiving an aerosol of vehicle alone. Loss of surfactant activity and increased alveolar surface tension were demonstrated by Wilhelmy balance studies of minced lung extracts, by a fall in static compliance, and by evidence of atelectasis and instability noted by gross observation and by in vivo microscopy. No significant changes in colloid oncotic pressure or pulmonary microvascular hydrostatic pressure were observed. These data suggest that pulmonary edema can be induced by increased alveolar surface tension and support the concept that one of the major roles of pulmonary surfactant is to prevent pulmonary edema. PMID- 2578445 TI - Compartmental analysis of the efflux of l-[3H]norepinephrine from isolated perfused rat lungs. AB - Isolated rat lungs, pretreated with 100 microM pargyline and 100 microM U-0521 (3',4'-dihydroxy-2-methylpropriophenone) to block metabolism of norepinephrine (NE), were perfused with 0.3 microM 3H-labeled l-norepinephrine (1-[3H]-NE) for 30 min. Efflux samples were then collected for 30 min during washout of the tissue with amine-free Krebs solution. Compartmental analysis (nonlinear least squares regression) of the efflux of tissue l-[3H]NE content vs. time indicates that NE is accumulated in a large slowly equilibrating compartment (t 1/2 = 58.15 +/- 6.84 min) in addition to distribution in the vascular (blue dextran tracer) and extracellular ([3H]sorbitol tracer) fluid compartments of the lung. Pretreatment of the lungs with 100 microM cocaine hydrochloride reduces the total l-[3H]NE space from 7.44 +/- 1.91 to 2.48 +/- 0.23 ml/g (P less than 0.05) by selectively decreasing the size of the slow NE compartment from 6.99 +/- 1.97 to 1.67 +/- 0.14 ml/g (P less than 0.05). The large size, cocaine sensitivity, and long efflux half time of this compartment suggest that neuronal uptake contributes to the pulmonary vascular inactivation of l-[3H]NE. PMID- 2578446 TI - In vitro RNA polymerase interaction with a restriction fragment containing the Escherichia coli origin of replication. AB - The interaction of RNA polymerase with a restriction fragment containing the origin of Escherichia coli replication (oriC) was examined by methods used to investigate transcription promoter activities. Interactions of RNA polymerase with oriC were determined and characterized by agarose gel exclusion under conditions of polymerase binding and RNA synthesis initiation. These interactions were further demonstrated and defined by nitrocellulose retention experiments under various reaction conditions. The binding of RNA polymerase to the oriC fragment was compared to binding to the tetracycline promoter (tet), a known strong promoter of transcription. Specific localization of the RNA polymerase oriC interaction was determined by restriction protection experiments. The binding of RNA polymerase was determined to be located near the HindIII site of oriC. These methods allowed the observation and characterization of a specific association of RNA polymerase with the origin of E. coli DNA replication. PMID- 2578447 TI - Two control systems modulate the level of glutaminyl-tRNA synthetase in Escherichia coli. AB - We studied the regulation of in vivo expression of Escherichia coli glutaminyl tRNA synthetase at the transcriptional and translational level by analysis of glnS mRNA and glutaminyl-tRNA synthetase levels under a variety of growth conditions. In addition, strains carrying fusions of the beta-galactosidase structural gene and the glnS promoter were constructed and subsequently used for glnS regulatory studies. The level of glutaminyl-tRNA synthetase increases with the increasing growth rate, with a concomitant though much larger increase in glnS mRNA levels. Thus, transcriptional control appears to mediate metabolic regulation. It is known that glnR5, a regulatory mutation unlinked to glnS, causes overproduction of glutaminyl-tRNA synthetase. Here we showed that the glnR5 product enhances transcription of glnS 10- to 15-fold. The glnR5 mutation does not affect metabolic control. Thus, glnS appears to be regulated by two different control systems affecting transcription. Furthermore, our results suggest post-transcriptional regulation of glutaminyl-tRNA synthetase. PMID- 2578448 TI - Cloning, sequence analysis, and expression of alteration of the mRNA stability gene (ams+) of Escherichia coli. AB - The ams+ gene, which influences the stability of mRNA in Escherichia coli was cloned in pBR322. The product of the gene, which is a 17,000-dalton protein, was expressed in expression vector pRC23, a derivative of pBR322. The molecular weight is consistent with sequencing analysis which shows that the gene contains 595 nucleotides and has an open reading frame of 149 amino acids. We discussed the possible role(s) of the ams+ gene product in affecting mRNA stability. PMID- 2578449 TI - Germination-initiated spores of Bacillus brevis Nagano retain their resistance properties. AB - Initiated spores and vegetative cells of the gramicidin S-producing Bacillus brevis Nagano were compared with respect to their resistance to various forms of stress (osmotic shock-starvation, exposure to ethanol, sonic oscillation, and heat). The resistance of initiated spores to all of these stress situations was considerably greater than that of vegetative cells and approached that of dormant spores. The period during which the initiated spores remained resistant to heat was extended by addition of gramicidin S. The antibiotic may therefore be of survival value to the species in nature by slowing down the development of initiated spores in the outgrowth phase of germination, thereby extending the period during which the cells are resistant to environmental stress. PMID- 2578450 TI - Quantitative immunochemical studies of myosin in Dictyostelium discoideum. AB - We have isolated monoclonal antibodies against myosin from the eukaryotic microorganism Dictyostelium discoideum. Immunoblot analysis using chymotryptic fragments of myosin has shown that the 17 antibodies are directed against at least five different sites on the myosin heavy chain. Using an antibody (M342) that reacts with an epitope on the tail portion of the myosin molecule, we have developed an assay to quantitate myosin in whole cells and subcellular fractions. Samples are deposited on nitrocellulose paper using a filtration manifold and are probed with metabolically labeled M342 antibodies. The assay is rapid and sensitive; it permits the measurement of myosin even in crude cell lysates that contain detergent. By use of the filtration immunoassay, we have found that myosin constitutes 0.72% of the total protein in vegetative amoebae. We have also determined that Triton-resistant cell residues (cytoskeletons or cortical actin matrices) prepared in the absence of ATP contain nearly half of the cell's myosin. If ATP is present, 98% of that myosin is released, although actin levels do not diminish. PMID- 2578451 TI - Antibodies recognizing different domains of the polymeric immunoglobulin receptor. AB - The receptor responsible for the transepithelial transport of IgA dimer antibodies is a transmembrane glycoprotein known as membrane secretory component (SCm). During transport, the membrane anchoring domain is cleaved and the ectoplasmic domain of the receptor (SCs) remains tightly bound to the IgA dimer in exosecretions. We have produced monoclonal antibodies with distinct specificities against both cytoplasmic and ectoplasmic epitopes of rabbit SCm. One antibody (anti-SC303) reacted both with SCm and free SCs but not with SCs bound to IgA dimer (SIgA). Therefore, it recognized an epitope close to the IgA dimer binding site. The other monoclonal antibody (anti-SC166), which was unable to react with SCs, bound to the 15-kDa cytoplasmic extension of the membrane spanning domain of the receptor. A polyclonal antibody (GaR-SC), raised in a goat against rabbit milk SCs, reacted with a subpopulation of SCs not recognized by the anti-SC303 monoclonal antibody and in addition also reacted with covalently bound sIgA. The three antibodies cross-reacted with rat SCm. We demonstrate the ability of the anti-SC166 monoclonal antibody to immunoadsorb subcellular organelles as a result of the cytoplasmic orientation of its epitope. Our data indicate that there are functional differences between the high- and low molecular-weight families of SC in terms of IgA dimer binding. PMID- 2578452 TI - Exposure of antigenic sites during immunization. Monoclonal antibodies to monomer of lactose repressor protein. AB - Monoclonal antibodies specific for the lactose repressor protein have been purified from three mouse hybridoma cell lines, and ascitic fluids from five other cell lines producing repressor antibodies have been assayed for immunoglobulin subclass and antigenic specificity. The chymotryptic core region (amino acids 57-360) of the repressor reacted with all antibodies examined, while no reaction with the NH2-terminal domain (1-56) could be detected. All of the purified antibodies and ascitic fluids reacted with the carboxyl-terminal fragment (amino acids 281-360) produced by cyanylation and base-catalyzed cleavage at the cysteine residues. Although none of the purified antibodies associated with native, tetrameric lac repressor, reaction was observed with repressor which had been denatured or dissociated into monomers by treatment with low levels of sodium dodecyl sulfate. Additionally, a mutant repressor which exists as a monomer in solution reacted with the antibodies in the absence of any denaturing treatments. These data indicate the carboxyl-terminal region is inaccessible in the intact repressor tetramer and further suggest that denaturation/dissociation of a protein during the initial immunologic challenge may result in the production of monoclonal antibodies to antigenic areas of the protein which are not exposed in the native conformation. PMID- 2578453 TI - Immunologic identification of a glycogen synthase 93,000-dalton subunit from rat heart and liver. AB - A polyclonal sheep antibody to rat heart glycogen synthase has been used for immunoblot analysis and immunoprecipitation of both rat heart and liver synthase. The purified antibody completely inhibits glycogen synthase activity in rat heart preparations and specifically blots to a 93-kDa band in the 10,000 X g supernatants of both heart and liver homogenates. Immunoprecipitation of in vitro translation products from rat heart or liver poly(A+) RNA yields a unique band with a molecular mass of 93 kDa. Thus the subunit molecular mass of active glycogen synthase in rat heart is 93 kDa. In rat liver at least one form of glycogen synthase also appears to have a molecular mass of 93 kDa. Protocols used to purify rat liver synthase yield a subunit of 80-87 kDa, which retains activity, but which is no longer recognized by the antibody. This suggests that 1) a specific antigenic sequence has been proteolytically removed from the NH2 or COOH terminus of the protein, or 2) that limited proteolysis has led to a conformational change in the enzyme such that the antibody binding site is no longer recognized. Either or both of these possibilities represent a significant alteration in the enzyme due to proteolysis. In vitro studies using synthase preparations having molecular masses less than 93 kDa must be interpreted with caution due to possible structural changes which occur during purification which may alter the regulation or covalent modification of synthase. PMID- 2578454 TI - 1,25-Dihydroxycholecalciferol and glucocorticosteroid regulation of adenylate cyclase in an osteoblast-like cell line. AB - To study regulation of the parathyroid hormone (PTH)-responsive adenylate cyclase of osteoblast-like cells by 1,25-dihydroxyvitamin D (1,25(OH)2D), cAMP levels and adenylate cyclase activity were assayed in the hormone-responsive ROS 17/2.8 rat osteosarcoma cell line. Treatment of cells with 1,25(OH)2D3: alone markedly attenuated the cAMP response to subsequent PTH; decreased adenylate cyclase stimulated by PTH; and completely antagonized the positive regulatory effects of cell treatment with glucocorticosteroid (GC) on these responses to PTH. Sterol receptor mediation was indicated by specificity for the 1,25(OH)2D metabolite and high sensitivity (half-maximal attenuation at 7 X 10(-11) M). The effects of 1,25(OH)2D and GC were primarily on the maximal activity of adenylate cyclase and not on sensitivity to Mg2+, guanine nucleotide, or PTH. GC augmentation of ROS 17/2.8 cell cAMP accumulation was also seen with another receptor agonist (beta adrenergic), cholera toxin or forskolin; 1,25(OH)2D antagonized all these GC effects. Opposing effects of GC and 1,25(OH)2D were seen as well on activation of the guanine nucleotide-binding regulatory protein (Ns) by guanyl-5'-yl imidodiphosphate and F- and on activation of the catalyst (C) by Mn2+. In contrast, with the activators other than PTH, cell treatment with 1,25(OH)2D in the absence of GC produced only minor attenuation of cAMP accumulation and no effect on adenylate cyclase activities. The data suggest that GC acts strongly on or near the PTH receptor-Ns complex in ROS 17/2.8 and to a lesser degree on the Ns-C interaction. Direct GC enhancement of C could not be concluded because of the influence of Ns on forskolin action and present data that Mn2+ does not uncouple Ns from C in this system. A GC effect on membrane structure or composition, as seen in other cell types, could explain these changes in adenylate cyclase function without the need to postulate multiple mechanisms. The data dissociate two 1,25(OH)2D effects, direct attenuation of activation of Ns via the PTH receptor and interference with the as yet undefined mechanism(s) of GC augmentation. These may represent dissimilar pathways of 1,25(OH)2D action on osteoblasts. PMID- 2578455 TI - Murinoglobulin, a novel protease inhibitor from murine plasma. Isolation, characterization, and comparison with murine alpha-macroglobulin and human alpha 2-macroglobulin. AB - Two glycoproteins having trypsin-protein esterase activity were purified to apparent homogeneity from murine plasma. One was alpha-macroglobulin, a homologue of human alpha-2-macroglobulin, while the other, tentatively named murinoglobulin, did not correspond to any of the known plasma protease inhibitors that have been well characterized in men or other mammals. Murinoglobulin contained about 7.6% carbohydrate and was composed of a single-polypeptide chain of Mr = 180,000 as judged by the equilibrium sedimentation analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Murinoglobulin did not cross-react immunologically with mouse alpha-macroglobulin nor with human alpha-2-macroglobulin. Protease-inhibiting properties of murinoglobulin were compared with those of mouse alpha-macroglobulin and human alpha-2-macroglobulin. All the three proteins inhibited trypsin, papain, and thermolysin, although they differed considerably in both the degree of inhibition and the binding stoichiometry of protease-inhibitor complexes. The two macroglobulins inhibited pepsin at pH 5.5, whereas murinoglobulin was inactivated at this pH. Murinoglobulin was more sensitive to methylamine than the two macroglobulins. No protein corresponding to murinoglobulin was detected in human plasma. PMID- 2578457 TI - Antigen-antibody interaction. The immunodominant region of EDP208 pili. AB - The EDP208 pilus contains a major antigenic determinant in the N-terminal dodecapeptide, as shown by E. A. Worobec, A. K. Taneja, R. S. Hodges, and W. Paranchych ((1983) J. Bacteriol. 153, 955-961). This peptide was chemically synthesized, coupled to bovine serum albumin with N-hydroxysuccinimidyl p-azido benzoate, and used in immunoblot and enzyme-linked immunosorbent assays to show it was capable of reacting with anti-EDP208 pilus antibodies. Antibodies raised against the synthetic peptide conjugate were also capable of reacting with whole pili in these assays. To further examine the specific residues responsible for the antigenicity of this site, several peptide analogs were chemically synthesized. The relative affinity of these peptides for anti-EDP208 pilus antibodies was determined by a competitive enzyme-linked immunosorbent assay using the Fab fragment of anti-EDP208 pilus immunoglobulin G. From these results we established that the antigenic region of this peptide was the N-terminal pentapeptide, N-acetyl-Thr-Asp-Leu-Leu-Ala, and the key residues responsible for the antibody-antigen interaction are the N-acetyl-Thr1, Leu3, and Leu4. Hydrophobic interactions involving the methyl of the acetyl group and the leucine side chains make the largest contributions to the antigen-antibody interaction, while a lesser contribution is made by the Thr1 hydroxyl. The side chains of Asp2 and Ala5 contribute only weakly to the stabilization of the antigen-antibody complex. PMID- 2578456 TI - Exit of nonglycosylated secretory proteins from the rough endoplasmic reticulum is asynchronous in the exocrine pancreas. AB - The path and synchrony of intracellular transport of 12 secretory proteins of the guinea pig exocrine pancreas have been studied in pulse-chase amino acid labeling experiments by quantitative analysis of the individual proteins recovered in subcellular fractions and extracellular samples. Protein fractionation was accomplished by two-dimensional isoelectric focusing/SDS-gel electrophoresis. Use of a double-label protocol allowed correction of the data on a protein-by-protein basis for leakage and adsorption artifacts which accompany tissue homogenization. All the labeled secretory (pro)enzymes, including their isoenzymic forms, were recovered in rough microsomal, Golgi-enriched and granule fractions during their transport to the cell surface. However, major asynchrony was observed at four levels: exit from the rough endoplasmic reticulum; transit through the Golgi complex; entry into granules; and discharge from the cell. Rapid transport rates were observed for trypsinogen, chymotrypsinogen 2, procarboxypeptidase A2, and lipase 2. Slow transport rates were observed for amylase and procarboxypeptidase B. In the presence of carbamylcholine or cholecystokinin stimulation, the times required for 40% discharge of labeled chymotrypsinogen 2, trypsinogen, amylase, and procarboxypeptidase B were 98, 102, 148, and 180 min, respectively. Transport rates did not correlate with isoelectric point, molecular weight, or the presence of carbohydrate. These data suggest that interactions occur within the rough endoplasmic reticulum, either between secretory (nonglyco)-proteins themselves or between such proteins and the cisternal face of the rough endoplasmic reticulum. PMID- 2578458 TI - A new moderately repetitive rat DNA sequence detected by a cloned 4.5 SI DNA. AB - 4.5 SI RNA is an abundant, noncapped, small nuclear RNA found in rodent cells. The 4.5 SI RNA is 98 or 99 nucleotides long and contains no modified nucleotides; it is synthesized by RNA polymerase III, is partly hydrogen-bonded to poly(A+) hnRNA, and was the first small nuclear RNA to be purified and sequenced (Busch, H., Reddy, R., Ruthblum, L., and Choi, Y. C. (1982) Annu. Rev. Biochem. 51, 617 654). In studies on the structure and organization of genes coding for this abundant RNA, it was found that this RNA is homologous to an apparently novel family of repetitive sequences. Two clones were characterized; one clone showed that its sequence is identical to the RNA in the first 92 residues and differed only in the last six nucleotides. In addition, the 3'-end of the sequence contained an A,T-rich region, and the sequence was flanked by a 15-nucleotide long direct repeat of AAAATATAGACACTG. The second clone characterized contained nucleotide sequences 1-57 corresponding to the RNA and was flanked by a 15 nucleotide long direct repeat. The structural features of these two DNAs are consistent with RNA-mediated DNA synthesis and integration of this DNA into the genome at random sites. It is estimated that there are about 10,000 copies of this family of sequences in the haploid rat genome. PMID- 2578459 TI - Bombolitins, a new class of mast cell degranulating peptides from the venom of the bumblebee Megabombus pennsylvanicus. AB - Five structurally related heptadecapeptides rich in hydrophobic amino acids have been discovered in the venom of the bumblebee Megabombus pennsylvanicus. We have named them bombolitin I (Ile-Lys-Ile-Thr-Thr-Met-Leu-Ala-Lys-Leu-Gly-Lys-Val-Leu Ala-His-Val-NH2 ), bombolitin II (Ser-Lys-Ile-Thr-Asp-Ile-Leu-Ala-Lys-Leu-Gly-Lys Val-Leu-Ala-His-Val-NH2 ), bombolitin III (Ile-Lys-Ile-Met-Asp-Ile-Leu-Ala-Lys Leu-Gly-Lys-Val-Leu-Ala-His-Val-NH2 ), bombolitin IV (Ile-Asn-Ile-Lys-Asp-Ile-Leu Ala-Lys-Leu-Val-Lys-Val-Leu-Gly-His-Val-NH2 ), and bombolitin V (Ile-Asn-Val-Leu Gly-Ile-Leu-Gly-Leu-Leu-Gly-Lys-Ala-Leu-Ser-His-Leu-NH2 ). Bombolitins are structurally and functionally very similar. They lyse erythrocytes and liposomes, release histamine from rat peritoneal mast cells, and stimulate phospholipase A2 from different sources. The threshold dose is 0.5-2.5 micrograms/ml depending on the peptide and the bioassay. Bombolitin V is as potent as the well-known melittin in lysing guinea pig erythrocytes (ED50 = 0.7 microgram/ml = 4 X 10(-7) M) and is 5 times more potent than mastoparan in causing mast cell degranulation, making it one of the most potent degranulating peptides discovered so far (ED50 = 2 micrograms/ml = 1.2 X 10(-6) M). The bombolitins represent a unique structural class of peptides but they have the same biological properties as melittin (from honeybees), mastoparan (wasps, hornets, and yellow jackets), and crabrolin (European hornets). This unusual circumstance (peptides with different amino acid sequences having the same biological properties) may be a manifestion of their amphiphilic nature, a property these peptides have in common. PMID- 2578460 TI - Structure of a precursor to the yeast mitochondrial tRNAMetf. Implications for the function of the tRNA synthesis locus. AB - A transcript from the yeast mitochondrial tRNAMetf gene has been isolated from a petite deletion mutant, ND40. RNA sequence analysis demonstrates that it has a 5' unprocessed extension of 28 nucleotides, and capping experiments with guanylyltransferase reveal that the first nucleotide has a 5' di- or triphosphate. A comparison of the RNA sequence with the tRNAMetf gene sequence reported here shows that transcription initiation occurs at a sequence homologous to a nonanucleotide segment implicated as a promoter element of yeast mitochondrial DNA. The 3' end of this transcript is identical to the mature tRNAMetf and carries a CCA sequence. The transcript can be processed in vitro to yield a mature tRNAMetf and thus appears to be a bona fide tRNA precursor. This tRNA precursor accumulates in the absence of the mitochondrial tRNA synthesis locus whereas mature tRNAMetf can be made from the same gene in the presence of the locus. This data provides clear and convincing evidence that the synthesis locus codes for a 5' tRNA processing function. PMID- 2578461 TI - Demonstration of two distinct tachykinin receptors in rat brain cortex. AB - Eledoisin and substance P are members of a class of peptides termed tachykinins. They share a similar spectrum of biological activities but their relative potencies in various pharmacological assays differ. We have investigated whether there is more than one receptor for these tachykinins in rat brain cortex membranes. 125I-Bolton Hunter-conjugated eledoisin specifically binds to rat brain cortex membranes with high affinity. The binding is inhibited over 95% by unlabeled eledoisin (6.6 microM). Scatchard analysis of the binding of this ligand is curvilinear suggesting that there are two binding sites with KD values of 0.9 +/- 0.7 nM and 20 +/- 10 nM. We tested various analogs and fragments of substance P and eledoisin for their ability to inhibit the binding of 125I-Bolton Hunter-conjugated eledoisin and 125I-Bolton Hunter-conjugated substance P to these membranes. The following peptides are more potent as inhibitors of the 125I Bolton Hunter-conjugated eledoisin binding site than of the 125I-Bolton Hunter conjugated substance P binding site: nonradioactive Bolton Hunter-conjugated eledoisin (greater than 100-fold), eledoisin (12-fold), kassinin (22-fold), neuromedin K (greater than 58-fold), and pyroglutamyl substance P(6 11)hexapeptide (4-fold). In contrast, substance P (21-fold), physalaemin (8 fold), and substance P methyl ester (1200-fold) were more potent as inhibitors of 125I-Bolton Hunter-conjugated substance P binding. These results suggest that these two ligands may bind to distinct receptors. 125I-Bolton Hunter-conjugated substance P binds specifically to rat parotid cell receptors, but 125I-Bolton Hunter-conjugated eledoisin does not, indicating that parotid cells contain only one of the receptor subtypes. The cortex membrane binding of both ligands is stimulated by low concentrations of MnCl2 (ED50 = 0.05 mM) and is inhibited by guanylyl-5'-(beta, gamma-imido)diphosphate (IC50 = 0.5 microM). PMID- 2578462 TI - Nucleotide sequence and expression of a Drosophila metallothionein. AB - A Drosophila melanogaster cDNA clone was isolated based on its more intense hybridization to RNA sequences from copper-fed larvae than from control larval RNA. This clone showed strong hybridization to mouse metallothionein I cDNA at reduced stringency. Its nucleotide sequence includes an open reading segment which codes for a 40-amino acid protein; this protein is identified as metallothionein based on its similarity to the amino-terminal portion of mammalian and crab metalloproteins. The 10 cysteine residues present occur in five pairs of near vicinal cysteines (Cys-X-Cys). This cDNA sequence hybridized to a 400-nucleotide polyadenylated RNA whose presence in the cells of the alimentary canal of larvae was stimulated by ingestion of cadmium or copper; in other tissues this RNA was present at much lower levels. Mercury, silver, and zinc induced metallothionein to a lesser extent. The level of metallothionein RNA increased very soon after the initiation of metal treatment and reached a maximum after approximately 36 h. PMID- 2578463 TI - The regulation of human factor XIIa by plasma proteinase inhibitors. AB - Studies of the inactivation of factor XIIa by plasma protease inhibitors in purified systems and in plasma were initiated to determine the relative importance of these inhibitors to the neutralization of factor XIIa. Factor XIIa was measured by the amidolysis of H-D-prolyl-L-phenylalanyl-L-arginine-p nitroanilide dihydrochloride or by coagulant activity. C1 inhibitor (C1INH), alpha 2-antiplasmin (alpha 2AP), alpha 2-macroglobulin (alpha 2M), and antithrombin III (ATIII) inhibited factor XIIa with second-order rate constants of 2.2 X 10(5), 1.1 X 10(4), 5.0 X 10(3), and 1.3 X 10(3) M-1 min-1. Factor XIIa activity was not affected by alpha 1-proteinase inhibitor. Incubation of 125I radiolabeled factor XIIa resulted in 1:1 stoichiometric complexes with C1INH (Mr 190,000), ATIII (Mr 125,000), and alpha 2AP (Mr 150,000 and 125,000) using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Incubation of 125I-Factor XIIa with alpha 2M resulted in a component of Mr 85,000 on a reduced sodium dodecyl sulfate-polyacrylamide gel, indicating that a subunit of factor XIIa was covalently bound to a proteolyzed portion of alpha 2M. The relative effectiveness of each inhibitor at plasma concentrations was 61:2:3:1 for C1INH, alpha 2AP, alpha 2M, and ATIII, respectively. Kinetic studies of the inactivation of purified factor XIIa added to various plasmas containing different concentrations of C1INH verified the predictions from the purified systems. Gel filtration of radiolabeled factor XIIa incubated with plasma confirmed that factor XIIa-C1INH was the major complex. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the complexes in plasma had the same molecular size as those with purified inhibitors. C1INH functions as the predominant inhibitor of factor XIIa in plasma. PMID- 2578464 TI - Pausing of RNA polymerase during in vitro transcription through the ilvB and ilvGEDA attenuator regions of Escherichia coli K12. AB - Synchronized single-round transcriptions, in vitro, from templates encoding the leader RNA of the ilvB and ilvGEDA operons result in the accumulation of a transcript consistent with RNA polymerase pausing after the 1:2 stem that could form in each of the leader RNAs. Addition of L-factor or guanosine 5' diphosphate,3-diphosphate extended the pause half-life obtained with the ilvB template; addition of L-factor and guanosine 5'-diphosphate,3'-diphosphate together had an additive effect on the pause half-life. L-factor also extended the pause half-life of the pause obtained with the ilvGEDA template; however, addition of guanosine 5'-diphosphate,3'-diphosphate did not. The results obtained are consistent with the model for attenuation proposed by Yanofsky et al. (Yanofsky, C., Das, A., Fisher, R., Kolter, R., and Berlin, V. (1984) UCLA Symposium of Gene Expression (Hamer, D., and Rosenberg, M., eds) pp. 295-310, Alan R. Liss, Inc., New York) in which transcriptional pausing after the synthesis of the 1:2 stem-loop closely couples transcription and translation of the leader region. PMID- 2578465 TI - The primase activity of DNA polymerase alpha from calf thymus. AB - The nearly homogeneous 9 S DNA polymerase alpha from calf thymus contains a primase activity that allows priming of DNA synthesis on single-stranded templates in the presence of ribonucleoside triphosphates. Both on synthetic and natural single-stranded templates, RNA primers of 8-15 nucleotides in length are formed. In the absence of dNTPs, primers of some hundred nucleotides in length are observable. ATP and/or GTP are required for the priming reaction. UTP and CTP cannot initiate the RNA synthesis. M13 single-stranded DNA can be converted to the nicked double helical form upon primase-primed replication by the 9 S enzyme. Priming occurs mostly at specific sites on the M13 genome and replication products of up to 6000 nucleotides in length are formed. In the presence of the single-stranded DNA binding protein from Escherichia coli, specificity of priming is strongly increased. The primase is inhibited by salt and actinomycin; it is insensitive to alpha-amanitin and N-ethylmaleimide. Due to the strong complex formation between DNA polymerase and primase, it has not been possible to separate the two activities of the multisubunit 9 S enzyme. PMID- 2578467 TI - Expression of the Caenorhabditis elegans collagen genes col-1 and col-2 is developmentally regulated. AB - The total collagen gene expression as well as the specific expression of two sequenced Caenorhabditis elegans collagen genes, col-1 and col-2, has been investigated. Northern blots of RNA isolated from animals at different developmental stages were probed under conditions that allow cross-hybridization of all collagen sequences. The majority of hybridization is to transcripts of 1.1 1.4 kilobases (kb) in length, with weak hybridization to some larger transcripts. Different size patterns, within the 1.1-1.4-kb ranges, are seen in RNAs from different developmental stages. Gene-specific probes were produced from the C. elegans collagen genes col-1 and col-2, and each was shown to hybridize to a single size transcript in the 1.1-1.4-kb region. The col-1 transcript was found in all the developmental stages examined, but its abundance varied between stages. The col-2 transcript was detected only in a single developmental stage, during formation of the dauer larvae. The 5' and the 3' ends of the col-1 and col 2 transcripts were determined by S1 nuclease digestion experiments. Both genes have the common "TATA" and "CAAT" box sequences preceding the 5' end of their transcripts and there is strong sequence homology in their 5' untranslated regions. Multiple copies of an eight-nucleotide repeat sequence were found upstream from both col-1 and col-2. PMID- 2578466 TI - Enzymatic modification of Novikoff hepatoma lamins A and C. AB - A significant increase in the molecular weights of lamin A and more so of lamin C was observed when isolated Novikoff hepatoma chromatin was incubated in the presence of Ca2+. This increase did not occur to any significant degree in similar preparations of normal rat liver nuclei. Although detectable in Coomassie Brilliant Blue stained gels, this increase to a higher molecular weight (by approximately 2000 Mr) was much more visible when the electrophoretically separated lamins were transferred to nitrocellulose sheets and stained (using peroxidase-antiperoxidase) with polyclonal antiserum to the three major lamin proteins. This modification could also be induced when whole Novikoff hepatoma cell lysates were incubated in the presence of calcium. Again, this change did not occur in normal rat liver cells treated in the same manner. Further analysis has provided evidence that this modification is most likely mediated by the transaminating activity of an intrinsic nuclear transglutaminase forming a cross link between the affected lamins and an unknown low molecular weight (approximately equal to 2000 Mr) moiety. PMID- 2578468 TI - Calcium flux and endogenous calcium content in isolated mammalian growth-plate chondrocytes, hyaline-cartilage chondrocytes, and hepatocytes. AB - The role of chondrocyte mitochondria in endochondral ossification has been the subject of intensive investigation and controversy. The purpose of this study was to quantitate the endogenous calcium content and the maximum capacity for calcium accumulation and release in isolated mammalian growth-plate chondrocytes and hyaline-cartilage chondrocytes. The results indicated that the mitochondria of the isolated growth-plate and hyaline-cartilage chondrocytes possess a greater endogenous calcium content, a greater capacity for calcium accumulation, and a larger labile Ca+2 pool than do the mitochondria of hepatocytes. Growth-plate and hyaline-cartilage mitochondria had an endogenous calcium content of 908 and 142 nanomoles of Ca+2 per milligram of mitochondrial protein. The growth-plate mitochondria had a maximum calcium capacity of 5249 nanomoles of Ca+2 per milligram of mitochondrial protein. In comparison, the mitochondria of hepatocytes had a much smaller endogenous-calcium content and a smaller maximum Ca+2 capacity: twenty-one and 3262 nanomoles of Ca+2 per milligram of mitochondrial protein, respectively. The mitochondrial labile-calcium pool in both growth-plate and hyaline-cartilage chondrocytes was twofold greater than that in the mitochondria of hepatocytes. Chondrocyte mitochondria released approximately 2400 nanomoles of Ca+2 per milligram of mitochondrial protein, whereas hepatocyte mitochondria released 1200 nanomoles of Ca+2 per milligram. These results suggest that the chondrocyte mitochondria are specialized for calcium transport and are important in the calcification of the extracellular matrix of the growth plate. PMID- 2578469 TI - Prophylaxis of deep-vein thrombosis after total hip replacement. Dextran and external pneumatic compression compared with 1.2 or 0.3 gram of aspirin daily. AB - The efficacy of three prophylactic regimens against deep venous thrombosis was assessed in 135 patients who were more than thirty-nine years old and had a total hip replacement. The three regimens were 1.2 grams of aspirin daily, 0.3 gram of aspirin daily, and external pneumatic compression of the calf and thigh combined with low-molecular-weight dextran that was given for three days, beginning during the operation. In all patients, detection of fresh thrombi was by the fibrinogen uptake test, cuff-impedance plethysmography, and venography. New venous thromboses developed in twenty-nine of forty-eight patients receiving 1.2 grams of aspirin and in twenty-six of forty-three receiving 0.3 gram of aspirin, indicating that the lower dose of aspirin had no advantage. Thromboembolic disease developed in only nine of forty-four patients who were on the regimen of external compression and dextran. This combination was significantly better than aspirin in both men and women. Dextran appeared to be associated with excessive bleeding when given in doses of more than 500 milliliters during the operation, but not when given in less than that amount. PMID- 2578470 TI - Treatment of human cell lines with 5-azacytidine may result in profound alterations in clonogenicity and growth rate. AB - Liquid medium cultures of three human cell lines (B-lymphoma, myeloma, and squamous lung carcinoma) with population-doubling times (PDT) and cloning efficiencies (CE) in the range of 32-43 h and 0.01-5.6%, respectively, were exposed to 5-azacytidine (5-azaC) for 3 d. The doses used (1-3 microM) were found to be nontoxic as measured by cell growth in liquid and semisolid agar medium and to be nonmutagenic as measured by the rate of generation of ouabain- and 6 thioguanine-resistant cell variants. After 5-azaC treatment, cell samples were subsequently harvested every day and assayed for their CE in semisolid agar medium. For each cell line, 30 to 42 individual clones were harvested at the day of maximal CE and expanded in liquid culture medium. PDT and CE were determined for each subclone about every 6 wk for 12 mo. The majority of the subclones had unaltered PDT and CE compared to the original lines. However, several clones had profoundly changed proliferative activity with PDT on approximately 12-14 h and/or CE 5 to greater than 50%. Some of the clones with altered growth properties reverted to PDT and/or CE values of untreated clones. However, a few clones of each line had stable alterations with PDT on 12-14 h and CE 5 to greater than 50%; these clones were all significantly hypomethylated. It is concluded that the human gene repertoire does contain genes that appropriately activated can result in growth properties with very short PDT and high CE (and comparable to animal cell lines), and that this activation may be obtained by 5 azaC treatment. It is conceivable that the procedure here described to alter growth properties of human cell lines may be applied to experimental situations, where alterations of cell growth properties are desired. PMID- 2578471 TI - Immunohistochemical localization of short chain cartilage collagen (type X) in avian tissues. AB - Monoclonal antibodies were produced against the recently described short chain cartilage collagen (type X collagen), and one (AC9) was extensively characterized and used for immunohistochemical localization studies on chick tissues. By competition enzyme-linked immunosorbent assay, antibody AC9 was observed to bind to an epitope within the helical domain of type X collagen and did not react with the other collagen types tested, including the minor cartilage collagens 1 alpha, 2 alpha, 3 alpha, and HMW-LMW. Indirect immunofluorescence analyses with this antibody were performed on unfixed cryostat sections from various skeletal and nonskeletal tissues. Only those of skeletal origin showed detectable reactivity. Within the cartilage portion of the 13-d-old embryonic tibiotarsus (a developing long bone) fluorescence was observed only in that region of the diaphysis containing hypertrophic chondrocytes. None was detectable in adjacent regions or in the epiphysis. Slight fluorescence was also present within the surrounding sleeve of periosteal bone. Consistent with these results, the antibody did not react with the cartilages of the trachea and sclera, which do not undergo hypertrophy during the stages examined. It did, however, lightly react with the parietal bones of the head, which form by intramembranous ossification. These results are consistent with our earlier biochemical analyses, which showed type X collagen to be a product of that subpopulation of chondrocytes that have undergone hypertrophy. In addition, either it or an immunologically cross reactive molecule is also present in bone, and exhibits a diminished fluorescent intensity as compared with hypertrophic cartilage. PMID- 2578472 TI - Subpopulations of fibroblasts from mouse skeletal muscle defined by clonal variation for 5' nucleotidase expression. AB - A primary cloning technique has been employed for the isolation of nine spontaneously transformed cell lines from mouse skeletal muscle. Four of these lines were isolated after selection for partial resistance to the purine (adenine) analog 2'6'diaminopurine and five were isolated from non-selected control dishes. Four of the nonselected lines and three of the selected lines demonstrated a fibroblastoid morphology in vitro. The other two cell lines (one from each group) were epithelioid. Two of the three selected fibroblastoid lines were found to contain significant quantities of the enzyme 5'nucleotidase (EC3.1.3.5), whereas the four nonselected fibroblastlike lines, one selected fibroblastlike line, and the two epithelioid lines did not. In the two cell lines expressing 5'nucleotidase activity, this expression was stable in the absence of selective pressure. Histochemical staining of mouse skeletal muscle for 5'nucleotidase activity demonstrated positive staining in the cells of small blood vessels and in a subset of the connective tissue cells. The bulk of the skeletal muscle tissue, however, had no detectable 5'nucleotidase activity. We propose that the two cultivatable types of fibroblastoid cell lines represent distinct classes of fibroblastlike cells in vivo, reflecting alternative states of stable cellular differentiation involving 5'nucleotidase expression. PMID- 2578473 TI - Production and characterization of interferon from endothelial cells. AB - The capacity of cultured bovine aortic, capillary, and corneal endothelial cells as well as of human umbilical cord endothelial cells to produce interferon (IFN) was investigated. The endothelial cells of the two species produced significant amounts of IFN in response to various viruses and poly (I) poly (C). The IFN produced by human umbilical cord endothelial cells was a mixture of alpha- and beta-IFN, as determined by neutralization with antibodies directed against these two types of IFNs as well as by measuring the antiviral activity on heterologous cells. Bovine endothelial cells also produced a mixture of at least two IFN subspecies, one of them labile at pH 2 and active on human cells and the other stable at pH 2 and inactive on human cells. PMID- 2578474 TI - Bacterial lipopolysaccharide induction of ornithine decarboxylase in the macrophage-like cell line RAW264: requirement of an inducible soluble factor. AB - Ornithine decarboxylase (ODC, EC 4.1.1.17) activity is induced in the RAW264 macrophage-like cell line by bacterial lipopolysaccharide (LPS). As little as 0.1 ng/ml LPS promoted an increase in ODC activity, while maximal ODC activity (30 fold above control) was induced with 1.0 microgram/ml LPS. An increase in ODC activity was detectable within 90 min of LPS addition. The LPS-induced increase in ODC activity was prevented by inhibitors of protein and RNA synthesis. The induction of the enzyme by LPS was not dependent on prostaglandin production. However, PGE2 (1 microgram/ml) and 8-bromo-cyclic AMP (1 mM), neither of which had an effect on ODC activity when added alone, each acted synergistically to enhance the LPS induction of ODC activity. Enzyme induction was not associated with an alteration in Km for ornithine, which remained constant at 0.04 mM. The extent of the increase in ODC in response to LPS increased with increasing cellular density. This relationship was dependent not on absolute cell density of the monolayer but on the cell number in relation to medium volume, and this dependence could be extrapolated to the origin. Addition of conditioned media from LPS-stimulated but not unstimulated cultures enhanced the ODC increase in sparsely plated cultures in response to a maximal concentration of LPS. The addition of polymyxin B, a reagent that blocks the effects of LPS, including the increase in ODC activity, did not totally inhibit the conditioned medium stimulation. This data indicates that two signals, LPS and a LPS-induced mediator, are involved in the induction of ODC activity in RAW264 cells. PMID- 2578476 TI - Adaptive regulation of neutral amino acid transport System A in rat H4 hepatoma cells. AB - Substrate regulation of System A transport activity in rat H4 hepatoma cells is described. The uptake of several amino acids was tested in the presence of system specific inhibitors. System A activity was increased in a RNA- and protein synthesis-dependent manner by amino acid deprivation of the cells (adaptive regulation), whereas transport by Systems ASC, N, y+, and L was unaffected. Unlike human fibroblasts, the H4 cells did not require serum to exhibit the depression of System A. At cell densities between 88 X 10(3) and 180 X 10(3) cells/cm2, the degree of adaptive regulation was inversely related to cell density. Both transport of AIB and adaptive regulation of System A were nearly abolished if either K+ or Li+ was substituted for Na+ in the medium. The presence of cycloheximide or tunicamycin blocked further increases in starvation-induced activity within 1 hr of addition, suggesting the involvement of a plasma membrane glycoprotein. In contrast, if the medium was supplemented with actinomycin after the stimulation of System A had begun, the activity continued to increase for an additional 2 hr before being slowed by the inhibitor. The contributions of trans inhibition and repression to the amino acid-induced decay of System A activity were estimated for several representative amino acids. In general, the System A activity in normal rat hepatocytes was much less sensitive to trans-inhibition than the corresponding activity in H4 hepatoma cells. The half-life values for the amino acid-dependent decay of System A ranged from 0.5 to 2.0 hr. PMID- 2578477 TI - The effects of lysosomotropic amines on protein degradation, migration of nonhistone proteins to the nucleus, and cathepsin D in lymphocytes. AB - Various lysosomotropic amines have two parallel effects in human lymphocytes: they inhibit the degradation of cellular proteins and increase the migration of nonhistone proteins (NHP) from the cytoplasm to the nucleus. The increased nuclear level of NHP is associated with increased cellular binding of [3H] actinomycin D, indicating an altered structure of chromatin. The agents inhibit the degradation of short- and long-lived proteins equally. Fractionation of the [3H] NHP of the nucleus according to pH 2.5-6.5 shows that [3H] NHP with a high rate of degradation in untreated cells correspond to [3H] NHP with a high rate of migration in cells treated with the agents. Eserine, amantadine, nicotine, atropine, benzylamine, and propranolol inhibit cathepsin D in concentrations causing proteolytic inhibition in cell cultures or in concentrations believed to be attained in lysosomes. The agents strongly inhibit the cellular accumulation of [3H] chloroquine. The data support the proposal that the migration of NHP from the cytoplasm to the nucleus is the direct consequence of inhibited degradation of these proteins in lysosomes by the amines. PMID- 2578475 TI - Linear relationship of phlorizin-binding capacity and hexose uptake during differentiation in a clone of LLC-PK1 cells. AB - With a clone of (Cl 4) of LLC-PK cells, which develop a high capacity for Na+ dependent hexose uptake over time (days) in culture, we show that increasing uptake capacity is paralleled by an increase in the number of phlorizin-binding sites in the population. The linear relationship between binding and hexose transport is the same whether the cells differentiate spontaneously or are induced by either methylisobutylxanthine or hexamethylene bisacetamide. The constancy of the relationship suggests that the primary factor in transport development is the number of transporters in the cells rather than other possible factors like a change in membrane potential or decreased efflux. The Kd for phlorizin binding is .08 +/- .04 microM, and corresponds to Ki of 0.10 microM for transport inhibition. The turnover number of the transporter is estimated to be 170 +/- 40 molecules per second of alpha-methyl glucoside. PMID- 2578478 TI - Antigenic analysis of Campylobacter flagellar protein and other proteins. AB - Outer membrane proteins of Campylobacter jejuni and other campylobacter species were analyzed for their antigenic potentials by immunoblotting. Polypeptides were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred electrophoretically, and reacted with rabbit antisera to C. jejuni. Each Campylobacter species analyzed demonstrated a unique outer membrane protein antigenic profile; interspecies antigen sharing was observed to be compatible with the degree of DNA relatedness between the species. The most highly conserved outer membrane protein antigen was the flagellum (molecular weight, 62,000). An aflagellate mutant was found to be untypable with the heat-labile system, in contrast to its parental isolate. The immunogenic potentials of C. jejuni proteins were examined by immunoblot analysis of sera from infected humans. Sera of convalescent patients, reacted with their homologous C. jejuni isolates, recognized a variety of campylobacter proteins. The most consistent immunogen in human infection was the flagellar protein. Patient sera assayed by the immunoblot technique were easily distinguished from control sera, which did not recognize specific campylobacter antigens. These findings suggest that the campylobacter flagellar protein is an essential determinant of the heat-labile antigen typing scheme and is the dominant immunogen recognized during C. jejuni infections in humans. PMID- 2578479 TI - Western blot analysis of the human antibody response to Campylobacter jejuni cellular antigens during gastrointestinal infection. AB - Western blot analysis was used to identify antigenic components of Campylobacter jejuni whole cells and outer membranes that elicit antibody responses in patients with campylobacter enteritis. Acute- and convalescent-phase sera from eight patients were analyzed for antibody activity against their homologous infecting strains and heterologous clinical isolates. Whole-cell and Sarkosyl-insoluble membrane components were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred electrophoretically to nitrocellulose paper for immunoblotting experiments. After the separated components were probed with patient sera, antibody binding was detected by autoradiography with 125I-protein A. Using this method, we detected several immunogenic components in whole cells and outer membranes. In the acute-phase response of some patients to infection, two to three components with approximate molecular weights of 66,000 (p66), 43,000 to 46,000 (major outer membrane protein), and 12,000 (p12) were detected in immunoblots. Convalescent-phase sera showed a more broad array of antibody binding to cell components. p66, shown to be campylobacter flagellin, was the major immunodominant component in almost all sera tested, however, p66 was not a major protein in Coomassie blue-stained gels. The major outer-membrane protein also bound to antibody, but with less intensity than p66. In general, the antibody specificity of patient sera was not limited to the homologous infecting strain, and antibodies cross-reacted with most components in heterologous strains. A low-molecular-weight component, identified as lipopolysaccharide with a modified silver stain, showed serological specificity for some patient sera. The results of this study showed that the antibody response of patients with campylobacter enteritis to C. jejuni antigens is variable. Flagellin appeared to be the major immunodominant component during infection. PMID- 2578480 TI - Specific and cross-reacting antigens of Staphylococcus aureus of human and canine origins. AB - Biotype -specificity of Staphylococcus aureus of human and canine origins has been found to be associated with thermolabile agglutinogens represented in S. aureus strains 17 and 61218, respectively. Both strains also have exhibited a common thermostable antigen. On that basis, absorbed antisera have been developed for the differentiation of S. aureus of the two biotypes. In the present study, still another thermostable agglutinogen was established, shared by strain 17 and some S. aureus strains of canine origin, as represented by S. aureus strain 887. These findings led to modification and enhanced specificity of the serological method of distinguishing S. aureus of the human biotype from S. aureus of the canine biotype. PMID- 2578481 TI - Fine needle aspiration cytology. AB - Fine needle aspiration cytology is an inexpensive, atraumatic technique for the diagnosis of disease sites. This paper describes the technique and illustrates how it may be applied to the management of tumours throughout the body. The limitations of the method, the dangers of false positive reports, and the inevitability of false negative diagnoses are emphasised. In a clinical context the method has much to offer by saving patients from inappropriate operations and investigations and allowing surgeons to plan quickly and more rationally. It is an economically valuable technique and deserves greater recognition. PMID- 2578482 TI - Serodiagnosis of ocular toxocariasis: a comparison of two antigens. AB - This study was designed to compare the sensitivity and specificity of enzyme linked immunosorbent assay (ELISA) for the serodiagnosis of ocular toxocariasis using Toxocara canis embryonated egg antigen (TEE) and toxocara excretory secretory or exoantigen (TEX) produced in vitro. TEE and TEX ELISA were comparably sensitive, but TEX ELISA was better able to discriminate between serum samples from patients with ocular toxocariasis and those from patients with retinoblastoma. In addition, preabsorption of sera with Ascaris suum embryonated egg antigen seemed to be essential to prevent false positive results with TEE ELISA but was not so critical for TEX-ELISA. Further studies are still required to standardise TEX for serodiagnosis. PMID- 2578483 TI - Demonstration of Mycobacterium tuberculosis in epoxy resin sections by the Ziehl Neelsen technique. PMID- 2578484 TI - Argentaffin and argyrophil reactions and serotonin content of endocrine tumours. AB - Sixty carcinoid tumours were tested in a retrospective study with an immunoperoxidase technique using a monoclonal antibody against serotonin immunoreactive sites, with argyrophil staining using the Grimelius technique, and with argentaffin staining using the Masson-Fontana technique. A good correlation between all three techniques in the diagnosis of ileal carcinoid tumour was found, but the immunoperoxidase technique showed greater sensitivity than the Masson-Fontana technique and greater specificity than the Grimelius technique in the diagnosis of foregut and hindgut carcinoid tumours. The immunoperoxidase technique with a monoclonal antibody against serotonin immunoreactive sites (YC5/45) is recommended as a sensitive and specific test for carcinoid tumours. The reactions in other endocrine tumours are also included. PMID- 2578486 TI - Ziehl-Neelsen staining of urine deposits in the diagnosis of genitourinary tuberculosis. PMID- 2578485 TI - Liver aspiration in the diagnosis of hepatocellular carcinoma in the Gambia. AB - Fine needle aspiration was used for the cytological diagnosis of hepatocellular carcinoma in 151 Gambian patients. Of 133 with hepatic tumours a correct positive cytological diagnosis was obtained in 116 (87.2%). This simple test was a safe and accurate diagnostic procedure. It is particularly suitable for use in countries where medical resources are limited and hepatocellular carcinoma is prevalent. PMID- 2578487 TI - Syva MicroTrak stains: their use in a routine laboratory. PMID- 2578488 TI - Substance P in the interpeduncular nucleus of the rat: normal distribution and the effects of deafferentation. AB - The interpeduncular nucleus (IPN) is a midbrain structure that receives its major afferents from the medial habenulae via the fasciculi retroflexi. Among the axons projecting to the IPN is a population of substance P (SP)-containing axons. The IPN has been subdivided into the central, dorsal, intermediate, rostral, and lateral subnuclei using cytoarchitectonic criteria. The distribution of SP among these subnuclei was determined by using Sternberger's ('79) peroxidase antiperoxidase technique. In the normal IPN the rostral subnucleus can be subdivided into two sectors on the basis of SP content. The ventral sector contains a moderate amount of SP and scattered SP positive perikarya. The dorsal cap of the rostral subnucleus contains denser SP than the ventral sector and it is continuous with the SP found in the dorsal subnucleus. The lateral subnuclei contain the densest SP found in the IPN and appear as laterally placed columns that expand in size caudally. The central and intermediate subnuclei contain very sparse SP. The fasciculus retroflexus was destroyed in 30 animals unilaterally or bilaterally and animals were perfused 4 days to 3 months postoperatively. After unilateral fascicular lesion, the SP in the rostral part of the ipsilateral lateral subnucleus is almost abolished, but caudally the decrease is confined to its lateral aspect. There is no visible decrease contralateral to the lesion. SP in the rostral part of the cap of the rostral subnucleus is decreased ipsilaterally but no loss is seen contralaterally or caudally. Animals with bilateral lesions show a great decrease in staining in the dorsal cap of the rostral subnucleus and the lateral subnuclei, with no decrease seen in the central, dorsal, or intermediate subnuclei. These results confirm that the origin of most of the SP in the IPN is fasciculus retroflexus fibers, but some of the SP arises from intrinsic SP perikarya located in the ventral sector of the rostral subnucleus and some may also arise from other sources. The areas of the IPN that receive bilateral SP projections from the fasciculus retroflexus (parts of the lateral and rostral subnuclei) show evidence for replacement of SP after lesion. This replacement implies sprouting or an increase in production of SP by remaining systems. PMID- 2578490 TI - Effect of conditioning lesion on axonal sprout formation at nodes of Ranvier. AB - The effect of a conditioning lesion on the time-course of axonal sprout formation after a subsequent testing lesion was evaluated in myelinated axons of the rat sciatic nerve. Transmission electron microscopy of longitudinal nerve sections was used to examine nodes of Ranvier located 200-500 micron proximal to the testing lesion. The conditioning lesion was a cut of the tibial nerve at the ankle; the testing lesion, made 2 weeks later, was a crush of the sciatic nerve at the hip. Sprouts were defined as unmyelinated evaginations of the nodal axolemma that (1) had reached the basement membrane of the Schwann cell, and (2) were located between the myelin sheath of the distal paranode and the basement membrane. Photomicrographs of the nodes at 9, 18, and 27 hours after the testing lesion were assigned to one of seven categories: normal, retracted, myelin degeneration, axonal degeneration, type A sprout formation (cytoskeleton absent), type B sprout formation (cytoskeleton present), and type B sprout degeneration. By 9 hours after the testing lesion, type B sprout formation was found in 9% of the nodes in control nerves (testing lesion alone) and 33% of those in conditioned nerves (P less than .01). A 33% incidence of type B sprout formation was not reached in control nerves until 27 hours after the testing lesion. Since the conditioning lesion was located 50 mm distal to the testing lesion and did not induce neuronal death, earlier sprout formation can be attributed to a neuronal response to the conditioning lesion rather than to a putative factor that arises from pre-degenerated fibers and acts on newly formed sprouts. PMID- 2578489 TI - Synaptic organization of substance P-like immunoreactive amacrine cells in goldfish retina. AB - A class of amacrine cells in the goldfish retina displays substance P-like immunoreactivity (SPIR). We studied the synaptic organization of SPIR amacrine cells by electron microscopical immunocytochemistry. Amacrine cells showing SPIR have processes which ramify in a very narrow band in layer 3 of the inner plexiform layer. SPIR is restricted to large dense-cored vesicles (DCVs), which are distributed throughout the dendrites. Processes labeled with SPIR contain a mixture of DCVs and numerous small agranular vesicles. Of 88 synaptic contracts analyzed, SPIR processes occurred as the presynaptic element 57 times and as the postsynaptic element 31 times. SPIR processes made synapses upon amacrine and ganglion cell dendrites with equal frequency and received synaptic input from both amacrine and bipolar cells. The stratification of SPIR amacrine cells in proximal sublamina a suggests that their synaptic interactions are restricted to "off" and "on-off" neurons. However, this is in contrast to published electrophysiological data. Possible explanations for this discrepancy are discussed in detail. PMID- 2578492 TI - Mechanisms of action and therapeutic role of corticosteroids in asthma. PMID- 2578491 TI - Dynamic computed tomography during arterial portography: the most sensitive examination for small hepatocellular carcinomas. AB - The efficacy of dynamic sequential CT with table incrementation during arterial portography (DSCTI-AP) in the detection of small hepatocellular carcinomas (HCC) (less than 3 cm in diameter and less than three in number) was analyzed in comparison with other imaging methods including radionuclide (RN) liver scans, ultrasound (US), CT, selective celiac angiography (SCA), and infusion hepatic angiography (IHA). The sensitivity of each study in detecting 19 cases of small HCC was as follows: RN, 16%; US, 63%; CT, 58%; SCA, 58%; IHA, 83%; and DSCTI-AP, 95%. Three of 19 cases were diagnosed only by DSCTI-AP and one case that could not be visualized by DSCTI-AP was opacified by IHA. Dynamic sequential CT with table incrementation during arterial portography was superior to IHA in visualizing small HCCs. PMID- 2578493 TI - Inhibitory effect of hydroxyzine on antigen-induced histamine release in vivo. AB - By use of a modified heat-suction, skin blister technique, we found that oral hydroxyzine, 25 mg four times a day, inhibits antigen-induced ultrastructural changes of mast cells and in vivo histamine release in the skin of ragweed sensitive individuals. To our knowledge this is the first demonstration that an orally active antihistamine can inhibit in vivo cutaneous anaphylactic reactions. PMID- 2578494 TI - The association between Dermatophagoides mites and the increasing prevalence of asthma in village communities within the Papua New Guinea highlands. AB - The prevalence of asthma among adults but not children living in eight South Fore villages of the Eastern Highlands of Papua New Guinea has risen dramatically over the past decade and now is 6 per 1000 in the age group less than 20 yr and 73 per 1000 in the age group more than 20 yr. Allergy to house dust mites appears to be a significant feature in the disease pathogenesis, and it is likely that this is associated with modifications to traditional lifestyles by the recent introduction of blankets and changes in sleeping habits that promote a more fertile environment for growth and multiplication of mites. Asthma is now provoked by a wide range of factors such as exertion, stress, and antecedent respiratory tract infections, which have always been common features of the South Fore way of life. This suggests that allergic reactivity may be the precursor of bronchial hyperreactivity that, once manifested, can be triggered by a variety of stimuli, not all of which are immunologic in origin. PMID- 2578496 TI - Monoclonal anti-human IgG antibodies for quantitation of allergen-specific IgG in human sera. AB - Eight monoclonal anti-human IgG antibodies were fully characterized and evaluated as possible reagents in solid phase radioimmunoassay for quantitating allergen specific IgG antibody. Four monoclonal antibodies (HG24D, HG2-14, HG2-18, and HG2 25) recognize CH2 domain of human IgG and bind to human IgG fixed to microtiter plate with high affinities. These monoclonal antibodies were more suitable than polyclonal rabbit anti-human IgG antibody in Phadebas RAST for honey bee venom specific IgG antibody. Nonspecific binding was much lower, and the slopes of standard curves were much steeper. In contrast to polyclonal antibody, the standard curve was hardly influenced by human serum IgG in sample diluent. These advantages of monoclonal antibodies that recognize CH2 domain of human IgG made it possible to quantitate egg white- and Dermatophagoides pteronyssinus-specific IgG antibodies with use of allergen disks prepared for IgE RAST. This property allows a single system to be used for measurement of IgG and IgE antibodies against clinically relevant allergens. PMID- 2578495 TI - The international collaborative study establishing the first international standard for timothy (Phleum pratense) grass pollen allergenic extract. AB - A selected candidate international reference preparation of timothy grass (Phleum pratense)-pollen extract was studied together with two other freeze-dried timothy pollen allergenic extracts in a multinational study. The collaborators used RAST inhibition, histamine release, quantitative immunoelectrophoresis (crossed immunoelectrophoresis/crossed radioimmunoelectrophoresis and rockets), isoelectric focusing, and other methods. The total allergenic potencies measured in RAST inhibition were evaluated for validity of linearity and parallel-line response. The relative concentrations of some important individual allergenic components were measured. The relative potencies for the total allergenic activity and the timothy components studied in each preparation were expressed relative to the selected candidate. This preparation was established in 1983 by the World Health Organization expert committee on biologic standardization as the international standard for timothy grass-pollen extracts with assigned units of 100,000 IU per ampule. PMID- 2578498 TI - A modified histochemical technique to visualize acetylcholinesterase-containing axons. AB - An improved histochemical method for light microscopic demonstration of acetylcholinesterase (AChE) has been developed. Axonal, dendritic, and perikaryal staining are well delineated, both in areas of low AChE content, such as cerebral cortex, and in areas of high AChE content, such as neostriatum. Axonal staining, including arborizations, stands out against a clear background devoid of diffuse reaction product. PMID- 2578497 TI - Nutrition intervention in developmental disabilities: an interdisciplinary approach. AB - The nutritional status of developmentally disabled persons is influenced by variables infrequently encountered in normal nutrition. The multitude of factors requires an approach to care that must incorporate information and assistance from a variety of disciplines. A model for viewing the network of variables is proposed as a tool for identifying voids in nutrition care and for developing appropriate plans that include interdisciplinary interactions for those persons with special needs. PMID- 2578499 TI - Immuno-ultrastructural localization of involucrin in squamous epithelium and cultured keratinocytes. AB - Involucrin immunoreactivity was localized ultrastructurally with protein A--gold in epidermis and cultured keratinocytes embedded in Lowicryl K4M. In the skin, immunoreactivity was found predominantly in cells of the granular layer and inner stratum corneum. The label was associated primarily with amorphous cytoplasmic material and especially keratohyaline granules. Some labeling was observed at the cell periphery, but little with keratin filaments. Tissue samples examined without aldehyde fixation showed relatively greater labeling in the outer stratum corneum than fixed tissue. In cultured cells, the labeling was also associated primarily with cytoplasmic granular material and to a lesser extent with the cell periphery. Upon treatment with the ionophore X537A, keratin filaments were found in aggregated arrays and the plasma membranes became convoluted. That involucrin immunoreactivity persisted in the cytoplasm in cultured cells and in vivo after cross-linking occurs could account for considerable isopeptide bonding detected in epidermal keratin fractions and indicates that not all the involucrin participates in envelope formation. PMID- 2578500 TI - An economical minichamber for immunohistochemical incubation. AB - A simple and economical "slide-minichamber" method for incubating tissue sections with antisera in immunohistochemical (peroxidase-antiperoxidase) staining procedures is described. The technique requires only materials routinely used in the laboratory. The method permits prolonged incubation of tissue sections with antiserum at 4 degrees C or at room temperature, use of small quantities of antiserum, and simultaneous incubation of two tissue sections with the same small quantity of antiserum, thereby allowing use of very dilute antisera and conservation of antisera when availability is limited. PMID- 2578501 TI - The use of monoclonal antibodies to estrogen receptors (ER) for immunoperoxidase detection of ER in paraffin sections of human breast cancer tissue. AB - Two monoclonal antibodies against MCF-7 human estrogen receptors were used for immunoperoxidase staining of paraffin sections of human breast cancer tissue. The staining was predominantly located in the nucleus of epithelial cells. Variation in the staining intensity was observed among individual cells. A significant positive correlation between the number of positively stained cells and cytosol estrogen receptor content (fmol of bound estrogen/mg of protein) was observed. The potential and the limitations of the present techniques are discussed. PMID- 2578502 TI - The cytolytic T lymphocyte receptor repertoire of H-2 disparate cells obtained from double parent chimeras. PMID- 2578503 TI - Specific accumulation of hapten-reactive T cells in contact sensitivity reaction sites. PMID- 2578504 TI - An in vitro system for the generation of suppressor cells and the requirement for B cells in their induction. AB - An in vitro method for the generation of effector suppressor cells (Ts3) was developed. By utilizing this protocol, it was possible to investigate both the cellular and genetic requirements for suppressor cell induction. It was determined that populations containing Ts3 cells can be induced after a 4-day culture of spleen cells and antigen. These Ts3 cells are similar to Ts3 cells generated by in vivo immunization. Both populations are I-J+, bind NP hapten, bind NP hapten, bear receptors which share NPb idiotypic determinants with anti NP antibodies, function during the effector phase of the immune response, and require activation with Ts2 cells. Generation of Ts3-containing populations required both nylon wool-nonadherent T cells and a nylon-adherent, B cell enriched population from an Igh-identical donor. T cells cultured with antigen alone or with syngeneic macrophages and antigen did not develop suppressive activity. Lytic treatment of the nylon-adherent population with a B cell-specific monoclonal antibody (J11d) removed the ability to generate suppressor cells. These results imply that the induction of suppressor T cells requires B lymphocytes, and that this induction process is dependent on Igh-linked gene products. PMID- 2578505 TI - Helper effects required during in vivo priming for a cytolytic response to the H Y antigen in nonresponder mice. AB - Induction of H-Y-specific cytotoxic T lymphocyte (CTL) responses in nonresponder female mice was attempted by i.v. injection of allogeneic male cells, followed by in vitro restimulation of recipient spleen cells with syngeneic male cells. Responses were obtained only in two strain combinations in which the recipients, although phenotypically nonresponders, carried responder alleles at class I major histocompatibility complex (MHC) loci, and the immunizing cells differed from the recipients at class II MHC loci. The two positive strain combinations were B10.A(2R) anti-B10.A(4R), and B10.GD anti-B10.D2(R101). In the first combination, both recipient and donor are nonresponders to H-Y, and the CTL are induced via a bystander effect of another CTL response to a previously undetected minor histocompatibility (H) antigen. This "carrier" antigen can only induce CTL against H-Y and itself when the immunizing cells express class II MHC molecules. Furthermore, the presence of H-Y and the carrier antigen on the same cell is a prerequisite for the generation of H-Y-specific CTL. In the second combination, the recipient is a nonresponder, whereas the donor is a responder. The two strains differ at only E alpha and E beta class II MHC loci. For the induction of CTL, H-Y and the foreign E molecule must be expressed on the same cells. Thus, the B10.D2(R101) cells that express E molecules on their surface probably provide the E-nonexpressor B10.GD recipients with a stimulus for the generation of H-Y specific T helper cells. The data are consistent with the notion that antigen specific class II MHC-restricted T helper cells are involved in the initiation of CTL responses to minor H antigens. PMID- 2578506 TI - LPS and specific T cell responses: interleukin 1 (IL 1)-independent amplification of antigen-specific T helper (TH) cell proliferation. AB - Lipopolysaccharide (LPS) fraction of endotoxin induces a significant potentiation of the antigen-specific proliferative response of T helper (TH) cell lines. This effect was obtained with LPS from different bacterial sources and reproduced with the lipid A moiety of endotoxin. Purified adherent spleen cells used as antigen presenting cells (APC) support this LPS-enhanced TH cell proliferation. In addition, the effect of endotoxin on specific TH cell responses was found to be absolutely dependent on the interaction between TH lymphocytes and APC through antigen-specific recognition. Thus, it was not observed in the absence of specific antigen or when monoclonal antibodies against class II MHC products or against L3T4 antigens were used to inhibit the T cell-APC interaction. Similarly, it was found that APC from the B6.CH-2bm12 mutant do not support the LPS-mediated enhancing effect. Furthermore, interleukin 1 (IL 1) appears not to be involved in LPS-mediated enhancement, and this effect is not reproduced by muramyl dipeptide (MDP)-mediated activation of APC. PMID- 2578507 TI - Regulation of clones responding to dextran B1355S. III. The thymic-independent and thymic-dependent antibody responses. AB - The primary antibody response of different mouse strains challenged with two antigenic forms of alpha (1-3) dextran, dextran B1355S and dextran-hemocyanin, was examined. Only BALB/c mice responded with both kappa and lambda antibodies. The kappa to lambda ratio was affected by factors such as the antigenic form of dextran, the time at which the serum was analyzed, and the priming regimen. Surprisingly, priming with hemocyanin in adjuvant increased the kappa portion of the response not only to dextran-hemocyanin but also to dextran B1355S. Other strains of mice responded with only lambda antibodies. These results extend our previous results on the analysis of dextran-specific B cell precursors. PMID- 2578508 TI - The use of haptenated-immunoglobulin molecules to induce tolerance in B cells from neonatal mice. AB - The role of the Fc region of trinitrophenylated (TNP)-immunoglobulins (Ig) in their ability to induce tolerance in immature B cells was examined. With the use of B cells from neonatal mice, tolerogens that could or could not bind to Fc receptors were assessed for their ability to induce tolerance. This was accomplished by tolerizing spleen cells in bulk culture and assessing the degree of tolerance by challenging the cells with the thymus-independent antigen TNP Brucella abortus (TNP-BA) in limiting dilution cultures. It was found that by using tolerogens containing 10 to 11 haptens per Ig molecule, immature B cells were very susceptible to tolerance induction. Mature B cells were not as susceptible. This increased susceptibility was independent of the Fc portion of the tolerogen, because TNP11-HGG and a TNP10-F(ab')2 induced equivalent degrees of unresponsiveness. When the TNP density was lowered to approximately five haptens per Ig molecule, those Ig molecules that contained Fc portions were superior tolerogens with the use of B cells from 6-day-old mice. Thus, a TNP4 HGG, TNP7-mouse IgG1, and TNP6-mouse IgG2a were more effective tolerogens than either TNP5-F(ab')2 or TNP6-mouse IgG3. These results confirm previous findings that immature B cells are inherently more susceptible to tolerance induction than mature B cells. They also suggest that very lightly haptenated Ig molecules may depend on Fc receptor-binding for effective tolerance induction. Finally, by means of a cytofluorograph, the surface IgD (sIgD) and sIgM phenotypes of splenic B cells from neonates of increasing age were determined. When comparing the phenotype of maturing cells with their tolerance susceptibilities, a correlation between the appearance of sIgD and the acquisition of resistance to tolerance was observed. PMID- 2578510 TI - Longitudinal analysis of three intrathecally produced immunoglobulin subpopulations in an MS patient. AB - Four murine anti-idiotypic (a-Id) hybridoma antibodies were produced against immunoglobulins (Ig) present in the cerebrospinal fluid (CSF) obtained from an MS patient 2 mo after the onset of disease. The four a-Id antibodies were shown to delineate idiotopes present on three distinct Ig subpopulations designated ID-19, ID-40, and ID-97. All three Ig subpopulations were produced in part by intrathecally localized B cells, together making up approximately 5% of the total CSF-Ig 2 mo after the onset of disease. Longitudinal analysis of the concentration of these Ig subpopulations in CSF showed that two subpopulations, ID-40 and ID-97, exhibited a regular relation to the clinical course of the disease, i.e., were decreased (ID-40) or increased (ID-97) in the first CSF sample obtained after two consecutive exacerbations. Screening of sera from 52 optic neuritis patients and 51 heterologous MS patients revealed that one MS patient's serum contained an Ig subpopulation that was idiotypically cross reactive with ID-97. So far, screening of these Ig subpopulations for reaction with several viruses (measles, parainfluenza type 1, influenza type A, cytomegalovirus, herpes simplex virus, rubella virus, poliovirus, murine encephalomyelitis viruses, and reovirus) and myelin basic protein has failed to reveal their antigen specificities. PMID- 2578511 TI - Measles-specific T cell clones derived from a twin with multiple sclerosis: genetic restriction studies. AB - The association between multiple sclerosis (MS) and HLA-DR2 suggests that the disease may be associated with an aberrant immune response, likely directed against an antigen of either viral or host origin. We have used measles virus specific T cell clones derived from a patient with MS to study genetic restriction patterns of antigen presentation by macrophage-enriched (E-) populations. Twenty-two clones proliferated in response to measles-infected Vero cells but not to mumps-infected or uninfected Veros. E- cells from both the autologous subject and her healthy, measles nonresponder identical twin were capable of presenting antigen to all clones. Studies with E- cells obtained from a panel of cell donors demonstrated clones which recognized antigen in association with D2/DR2, DR4, subgroups of DR4, and SB3. Three clones recognized antigen only in association with the autologous or twin's cells, but not with other sets of HLA-matched E-cells obtained from healthy donors or from other patients with MS. These studies indicate that the differing responses to measles virus demonstrated by these two identical twins are not explained by alterations in the interactions between antigen-presenting cells and T cells. Furthermore, at the clonal level, no preferential role is seen for HLA-DR2 as the restricting element for presentation of measles virus to these clones. PMID- 2578509 TI - Lymphoma models for B cell activation and tolerance. I. Conditions for the anti mu-dependent stimulation of growth in NBL, a nude B cell lymphoma. AB - NBL is a spontaneous B cell lymphoma that originated in NIH Swiss nude mouse, and has been maintained as an in vitro line for 4 yr in our laboratory. It is surface IgM positive and expresses several B cell markers including Fc receptors, as well as Ly-1. Although clones of NBL will grow in serum-containing medium, this cell line enters a quiescent state in serum-free culture. However, in the presence of affinity-purified or monoclonal anti-mu reagents, NBL increases its rate of proliferation as measured by thymidine incorporation or in absolute cell numbers. This stimulation is specific for mu-chain, because it does not occur with anti beta 2 microglobulin, irrelevant nonbinding antibodies, or with monoclonal anti-B cell lineage markers. Bivalent anti-mu is required, and no consistent Fc-mediated inhibition of growth has been detected. Stimulation of NBL occurs optimally at critical cell densities (greater than 3 X 10(3)/well) in the absence of serum. Therefore, we reasoned that NBL either produced or was receptive to known B cell growth factors. Although no classic IL 1 was detected in NBL supernatants, some BCGF-I-like activity was found. Finally, in the presence of LPS, both spontaneous and anti-mu-stimulated NBL growth was inhibited, a result suggesting maturation of this lymphoma. These results suggest that NBL represents an excellent model to study the growth and differentiation of B cell subsets. PMID- 2578512 TI - The nature of the defect in experimental allergic encephalomyelitis (EAE) resistant Lewis (Le-R) rats. AB - Recently, a colony of Lewis rats has been described which is resistant to experimental allergic encephalomyelitis (EAE). These rats, termed Le-R, are still histocompatible with other Lewis rats. The genetic defect which results in EAE resistance was shown not to be linked to the RT1.B (Ir) region of the MHC. Myelin basic protein (BP)-sensitization of Le-R rats induces cells capable of mounting a proliferative response to BP in culture but incapable of transferring EAE after culture with BP. The present study demonstrates that the latter deficiency can be overcome either by incorporating lipopolysaccharide (LPS) in the BP-culture medium or by simultaneous transfer of LPS-activated antigen-nonspecific spleen cells with the BP-sensitized cells. The BP-sensitized Le-R cells fail to transfer EAE due to their inability to initiate lesions in the CNS. LPS, working through an antigen-nonspecific cell or cell products, can correct the defect in the Le-R cells such that the antigen-specific cells become capable of initiating CNS lesions which lead to development of clinical EAE. PMID- 2578513 TI - Monoclonal antibodies to murine gamma-interferon which differentially modulate macrophage activation and antiviral activity. AB - Four monoclonal IgG antibodies to purified, recombinant murine gamma-interferon (rIFN-gamma) have been produced by fusion of immune hamster splenocytes with HAT sensitive murine myeloma cells. Specificity was confirmed either with an enzyme linked immunosorbent assay (ELISA) that used immobilized rIFN-gamma or with a radioimmunoassay that employed soluble 125I-rIFN-gamma and heat-killed, fixed Staphylococcus aureus-bearing Protein A. Competition binding experiments suggested that the monoclonal antibodies (MoAb) displayed two distinct epitope specificities: one displayed by H1 and H2, and the other displayed by H21 and H22. By using murine-human recombinant IFN-gamma hybrid molecules, the H1/H2 epitope was shown to depend on the amino-terminus of IFN-gamma, whereas the H21/H22 epitope was formed by the carboxy-terminal amino acid sequence. The MoAb also reacted with natural IFN-gamma. When bound to a surface, all four MoAb, but not normal hamster IgG, removed 100% of the antiviral and MAF activities present in supernatants of cultures of the murine 24/G1 T cell hybridoma. In free solution, all four antibodies inhibited IFN-gamma dependent antiviral activity, but with different efficiencies. Soluble H21/H22 also blocked all of the 24/G1 derived activity that induces nonspecific tumoricidal activity in macrophages (MAF) while H1/H2 enhanced MAF activity. The differential inhibitory or enhancing activities of H21 or H1 reflected their ability to inhibit or enhance binding of 125I-rIFN-gamma to macrophages, respectively. Soluble H21/H22 and solid-phase H1/H2 inhibited 100% of the MAF, microbicidal, and Ia-inducing activities from lymphokine preparations produced by mitogen stimulation of normal murine splenic cells. These results help to establish definitive structure-function relationships for the IFN-gamma molecule, and indicate that IFN-gamma is the primary lymphokine responsible for inducing nonspecific tumoricidal activity and Ia antigen expression, and for enhancing microbicidal activity in macrophages. PMID- 2578514 TI - TCGF (IL 2)-receptor inducing factor(s). I. Regulation of IL 2 receptor on a natural killer-like cell line (YT cells). AB - A continuous cell line (YT cells) with inducible receptor for T cell growth factor (TCGF)/interleukin 2 (IL 2) was established from a 15-yr-old boy with acute lymphoblastic lymphoma and thymoma. YT cells were tetraploid, having 4q+ chromosomal markers, and proliferated continuously in vitro without conditioned medium (CM) or IL 2. They were weakly positive for OKT9, OKT11, and Tac antigen (Ag), a determinant closely associated with the receptor for IL 2 (IL 2-R), and were negative for OKT1, OKT3, OKT4, and OKT8 Ag. YT cells also expressed HNK-1 Ag and Fc receptors for IgG, which are expressed on natural killer (NK) cells. They retained a killing activity against human cell lines, including K562 (myeloid), T, and B cell lines. Unlike Tac Ag/IL 2-R(+) cell lines derived from adult T cell leukemia (ATL), YT cells were negative for HTLV, as proved by Southern blotting with cDNA for viral DNA. The expression of Tac Ag was markedly enhanced in 18 hr, when YT cells were incubated with CM from PHA-stimulated peripheral blood leukocytes (PBL) or spleen cells, as determined by immunofluorescence by using flow cytometry and binding assay with 125I-anti-Tac antibody (Ab). The binding study with 125I-labeled recombinant IL 2 showed 3.2 X 10(4) IL 2 receptor sites on YT cells precultured with CM. PHA-P and Con A neither agglutinate nor enhance the expression of IL 2-R/Tac antigen on these non-T cell line cells. Furthermore, neither recombinant IL 2 nor gamma-interferon could induce IL 2-R on YT cells, suggesting the presence of a unique IL 2-R inducing factor in PBL or spleen CM. Unlike Tac Ag on HTLV(+), ATL-derived cell lines (Hut-102, MT-1, ATL-2), the expression of Tac Ag on YT cells was down-regulated by anti-Tac Ab. The induction of Tac Ag/IL 2-R on YT cells seemed specific, because the enhancement of Tac Ag expression was not associated with that of Ia Ag and T9/transferrin receptor. PMID- 2578515 TI - Investigations into the nature of Igh-V region-restricted T cell interactions by using antibodies to antigens on methylcholanthrene-induced sarcomas. I. Analysis of an Igh-V-restricted suppressor-inducer factor. AB - We have previously demonstrated the relationship between antigens on BALB/c methylcholanthrene (MC)-induced fibrosarcomas and T cell regulatory molecules by using a variety of antisera raised to these sarcomas in BALB/c and BALB/c X C57BL/6 (CB6F1) mice. One such pool of antiserum, a CB6F1 anti-CMS 4 (Pool XIV) serum, was used to investigate the nature of the T cell regulatory structures recognized by these antibodies. Pool XIV antiserum was capable of blocking the induction of feedback suppression by Ly-1 TsiF, an SRBC-specific suppressor T cell factor secreted by Ly-1+, 2- I-J+ T cells. Ly-1 TsiF induces suppression by interacting with an Ly-1+,2+ I-J+ T cell target. Successful interaction of Ly-1 TsiF with its target cell requires genetic homology between inducer and target cells at the variable region of the immunoglobulin heavy chain gene complex (Igh V). The addition of Pool XIV antiserum to primary in vitro anti-SRBC cultures resulted in blocking the ability of Ly-1 TsiF from Igha (BALB/c) and Ighj (CBA/J) mice to induce suppression on syngeneic cells, whereas suppression induced by Ly 1 TsiF in Ighb (B6), Ighc (DBA/2), Ighd (A/J), and Ighe (AKR) mice are unaffected by addition of the Pool XIV antiserum. The ability of Pool XIV antiserum to block Ly-1 TsiF activity is linked to the Igh region, because Pool XIV antiserum can block Ly-1 TsiF from BALB/c (H-2d, Igha) and the Igh congenic B.C9 (H-2b, Igha) while not affecting Ly-1 TsiF activity on B6 (H-2b, Ighb) or its Igh congenic C.B20 (H-2d, Ighb). In CB6F1 animals, Pool XIV antiserum could block the ability of CB6F1 Ly-1 TsiF to suppress BALB/c spleen cells but not B6 spleen cells. Conversely, Pool XIV antiserum could block the ability of BALB/c Ly-1 TsiF to suppress CB6F1 spleen cells, whereas B6 Ly-1 TsiF showed normal suppressive activity in the presence of Pool XIV antiserum. In contrast, Pool XIV was capable of blocking the ability of Ly-1 TsiF from BALB/c into CB6F1 bone marrow chimeras (BMC) to suppress both BALB/c and B6 mice, whereas the activity of Ly-1 TsiF from B6 into CB6F1 BMC on BALB/c or B6 spleen cells was unaffected by the addition of Pool XIV antiserum. We then investigated the molecular nature of the molecule recognized by Pool XIV antiserum on the Ly-1 TsiF.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2578517 TI - In vivo activity of affinity-purified helper factor from antigen-specific helper clone. AB - Supernatant from culture of a virally transformed OVA-specific helper T clone (C 41) was examined for the presence of soluble helper factor. Inoculation of helper clone supernatant into DNP-KLH-primed mice enhanced the IgG anti-DNP response when given with DNP-OVA. The C-41 supernatant did not trigger the DNP-primed B cells in mice when injected with hapten (DNP) coupled to an unrelated carrier (BSA). The carrier-dependent helper activity of C-41 supernatant in vivo demonstrates the presence of an antigen-specific T helper factor in the media of the cultured helper clone. Extensive immunization of F1(C57BL X BALB/c) mice with the helper clone resulted in the production of anti C-41 antibodies. Monoclonal antibodies prepared from the immunized mice were screened for specificity of binding to other transformed T lines and clones, some specific to OVA. Monoclonal antibodies that stained the C-41 cells exclusively were considered clone specific. Supernatants of the helper clone were passed over columns of anti-clone specific antibodies. The eluates from three antibodies were active as antigen specific helper factor, i.e., they elevated the IgG anti-DNP response in vivo in a linked recognition fashion in the presence of DNP-OVA. The affinity-purified factor was inactive when injected with DNP-BSA or DNP-BSA + OVA. Thus, we describe the antigen-specific immune function of a clone-produced helper factor in normal mice. PMID- 2578516 TI - Pregnancy-associated growth factor. II. A T-dependent polyclonal activator of human adult peripheral blood lymphocytes (PBL). AB - This study examined the ability of pregnancy-associated growth factor (PAGF), a substance found in crude human chorionic gonadotropin (hCG), to induce plaque forming cells (PFC) in cultured human peripheral blood lymphocytes (PBL). PAGF, 0.25 to 1 mg/ml, induced maximal PFC at 6 to 7 days as measured by the staphylococcal protein A-coupled SRBC reverse hemolytic plaque assay with a rabbit anti-human Ig antiserum. PAGF-induced PFC/culture ranged from 1800 to 39,000 with a mean of 11,524 in unfractionated PBL (N = 24), as compared to 540 to 77,840 with a mean of 17,303 for pokeweed (PWM) (N = 22). Comparison of PAGF- and PWM-induced PFC showed that both induced specific IgG, IgA, and IgM PFC. In most individuals, PAGF induced more IgM and PWM more IgG PFC. The kappa: lambda ratio was 1.5 for unstimulated PBL, and approximately 3.5 for PAGF and PWM. To see if PAGF was a T-dependent polyclonal activator of B cells, T and non-T populations were obtained by SRBC rosettes and negatively selected T4 and T8 cells by complement-mediated lysis of SRBC+(T) cells. Only the recombined subsets which included T4 cells and non-T cells supported PAGF- and PWM-induced PFC. These data indicate that PAGF, a substance derived from commercial extracts of pregnancy urine, is a T4-dependent polyclonal activator of normal human B cells. PMID- 2578518 TI - Murine transfer factor. II. Transfer of delayed hypersensitivity to synthetic antigens. AB - Synthetic polyaminoacid antigens were used to examine the specificity of transfer of delayed-type hypersensitivity with spleen cell dialysates in mice. Dialysates from GAT10-sensitized donors sensitized recipients to GAT10, but not GLA5 or cytochrome c. Dialysates from GLA5-sensitized donors sensitized recipients to GLA5, but not GAT10 or cytochrome c. We interpret these findings as consistent with the concept that passive transfer of delayed hypersensitivity with dialyzable materials is an immunologically specific event. PMID- 2578519 TI - Polymorphism of murine major histocompatibility Class I antigen: assignment of putative allodeterminants to distinct positions of the amino acid sequence within the first external domain of the antigen. AB - Forty-five new monoclonal antibodies reacting with the mouse H-2Dd antigen have been established. The specificities of 34 of these antibodies were mapped into the first external domain (N) of the Dd antigen by testing reactivities with the products of mosaic H-2 genes in which the coding sequences of the first and/or the second external domains of the H-2Dd genes were recombined in vitro with the remaining portion of the H-2Ld gene. These antibodies reacted with at least 13 distinct allodeterminants located in the N domain, composed of 91 amino acids, as judged from panel tests carried out on various H-2 haplotypes. To assign possible positions of antigenic determinants of these and other anti-H-2Dd antibodies, we compared primary sequences of seven H-2 antigens and searched for correspondence between the pattern of amino acid substitutions in the N domain, allowing 15 positions to be assigned for the antigenic sites. These putative antigenic determinants were assessed for possible relationships with several parameters of protein secondary structure postulated according to predictive methods. Many of these sites appear to be associated with greatest local hydrophilicity, known to correlate with sites of antibody binding in various proteins. We therefore propose that some of the correspondences found in this work represent structural correlates of allodeterminants. PMID- 2578520 TI - Delineation of three subsets of class I human T antigens (HTA) on Molt-4 cells: serologic and regulatory relationship to HLA class I antigens. AB - Three subsets of class I human T antigens (HTA) were serologically identified on the surface of the Molt-4 T lymphoma cell line. The HTA 1 subset is defined by NAI/34, D47, or 10H3.9 cross-reactive m.Ab. and by BL6 m.Ab. The HTA 2 and HTA 3 subsets are defined by M241 and 4A7.6 m.Ab., respectively. We obtained no evidence of any additional HTA subset. The different HTA antigens share only few epitopes with human leukocyte antigens (HLA-A, -B, and -C). Interestingly, these epitopes all belong to the same cluster defined on HLA class I molecules, but differ from one HTA subset to another. These results would therefore suggest that HTA and HLA class I antigens display a limited structural homology, but have a conserved epitopic area whose detailed structure differs for each HTA subset. Furthermore, the cell surface expression of each HTA class I molecule type is differently enhanced by natural interferon (IFN)-alpha or -gamma. This result additionally supports the serologic delineation of HTA subsets, and suggests that the corresponding genes in Molt-4 cells, are subjected to distinct regulations. PMID- 2578521 TI - Evidence that autoreactive T hybridomas recognize multiple epitopes on the I-Ak molecule. AB - In this study we attempt to define the number of determinants on the I-Ak molecule recognized by a panel of autoreactive I-Ak-specific T cell hybridomas. The recognition sites or histotopes of a panel of autoreactive I-Ak-restricted T cell hybridomas was determined in two ways: 1) by their ability to be activated by a panel of A betak and A alphak mutant antigen-presenting cell lines, and 2) by inhibition of activation by anti-I-Ak monoclonal antibodies. The results are most consistent with the presence of multiple distinct recognition sites on the I Ak molecule. However, an alternative explanation, that the T cell hybridomas recognize the same self epitope on Class II molecules, but with different affinity, cannot be excluded. PMID- 2578523 TI - Release of histamine and arachidonate from mouse mast cells induced by glycosylation-enhancing factor and bradykinin. AB - Stimulation of normal rat splenic T cells with pertussigen (lymphocytosis promoting factor from Bordetella pertussis) resulted in the release of a soluble factor that enhanced the assembly of N-linked oligosaccharides to IgE-binding factors during their biosynthesis. The glycosylation-enhancing factor (GEF) is a kallikrein-like enzyme and is purified by absorption to p-aminobenzamidine Agarose followed by elution with benzamidine. Incubation of normal mouse mast cells with affinity-purified GEF or bradykinin, a product of cleavage of kininogen by kallikrein, resulted in the release of histamine and arachidonate from the cells. Passive sensitization of mast cells with mouse IgE antibody, followed by pretreatment of the cells with a suboptimal concentration of GEF, resulted in an enhancement of antigen-induced histamine release. It was found that GEF and bradykinin induced the same biochemical events in mast cells as those induced by bridging of IgE receptors. Both GEF and bradykinin induced phospholipid methylation and an increase in intracellular cyclic AMP (cAMP). Incorporation of 3H-methyl groups into phospholipids and intracellular cAMP levels both reached a maximum 30 sec after challenge with GEF or bradykinin, and then declined to base-line levels within 2 to 3 min. These biochemical events were followed by 45Ca influx and histamine release; 45Ca uptake reached a plateau value at 2 min, and histamine release reached a maximum at 5 to 8 min. The initial rise in cAMP induced by GEF (or bradykinin) was not inhibited by indomethacin, indicating that the activation of adenylate cyclase is not the result of prostaglandin synthesis. In both IgE-mediated and GEF-induced histamine release, inhibitors of methyltransferases, such as 3-deaza adenosine and L homocysteine thiolactone, inhibited not only phospholipid methylation but also the cAMP rise and subsequent Ca2+ uptake and histamine release. The results indicate that GEF induces activation of methyltransferases and that phospholipid methylation is involved in the cAMP rise, Ca2+ uptake, and histamine release. The induction of the same biochemical events in the same sequence by bridging of IgE receptors and by GEF (bradykinin) supports the hypothesis that receptor bridging induces the activation of serine protease(s) and cleavage products of this enzyme in turn activate methyltransferases in mast cells. PMID- 2578522 TI - Activation of the alternative pathway of complement by human peripheral nerve myelin. AB - Destruction of peripheral nerve myelin (PNM) occurs as a consequence of a variety of pathologic conditions affecting the peripheral nervous system. In certain primary demyelinating neuropathies, several lines of evidence implicate complement in the pathogenesis of demyelination. In this study we demonstrate that human PNM consumes complement in vitro in the absence of specific antibody or C1 activation. Furthermore, activation of complement by PNM via the alternative pathway was shown by cleavage of C3 in normal human serum (NHS) and of B in C2-deficient serum (C2d-HS). Increasing consumption of hemolytic activity of C3 in Mg-EGTA-treated NHS was also noted with increasing amounts of PNM. Pronase treatment of PNM abolished C3 consumption, suggesting that a protein component exposed on the surface of myelin participated in the alternative pathway activation. When P0, the major amphiphilic glycoprotein of PNM, was incorporated into artificial lipid bilayers, the Po-liposomes consumed C3 activity in NHS containing Mg-EGTA. Pronase treatment of Po-liposomes abolished C3 consumption to the level of control liposomes, indicating that P0 was responsible for at least part of the activation seen with peripheral myelin. PMID- 2578524 TI - Subspecies- and species-specific antigens of Leishmania mexicana characterized by monoclonal antibodies. AB - Monoclonal antibodies have been produced that are specific for the reference stocks of Leishmania mexicana species and subspecies L. mexicana mexicana(L11, M379), L. mexicana amazonensis (WR303, H6, LV72), and L. mexicana pifanoi (L20). The specificities of these antibodies were confirmed by analyses employing an indirect radioimmune binding assay and 107 stocks of New World Leishmania. The molecules associated with these species- and subspecies-specific determinants have been characterized by Western blot analysis and consist of mainly low m.w. (11,000 to 50,000) membrane-associated components. PMID- 2578525 TI - Induction of protective immunity against Schistosoma mansoni by a nonliving vaccine is dependent on the method of antigen presentation. AB - A preparation of nonliving parasite antigens containing both soluble and particulate components of frozen-and-thawed invasive larvae was used to immunize C57BL/6J mice against challenge Schistosoma mansoni infection. The method of antigen presentation was observed to be critical to the ability of this preparation to induce protective immunity, because intradermal administration in conjunction with a bacterial adjuvant (BCG) resulted in strong protection against challenge parasites (51% reduction in worm burden in six experiments), whereas i.v. injection of the same antigenic preparation was completely ineffective. Induction of resistance was accompanied by specific immune responsiveness toward schistosome antigens. Protection correlated more closely with sensitization for specific delayed hypersensitivity than with elicitation of circulating antibodies to larval surface antigens or immediate hypersensitivity in these models. These results suggest that it will be possible to design a defined vaccine against S. mansoni infection, but that identification of the route of antigen presentation that most effectively elicits relevant immune effector mechanisms will be crucial to the success of any vaccination protocol involving nonliving antigens. PMID- 2578526 TI - Selective localization of tumor-immune spleen cells at the tumor challenge site after adoptive transfer of line 10 tumor immunity in strain 2 guinea pigs. AB - In this study, the distribution of immune spleen cells was investigated after adoptive transfer of immunity in inbred strain 2 guinea pigs. Spleen cells obtained from line 10 immune donor animals became specifically restimulated in vitro with 3 M KCl-extracted line 10 soluble proteins, but not with 3 M KCl extracted line 1 or liver proteins. After 4 days culture in vitro, these specifically restimulated immune spleen cells retained their antitumor activity in vivo after adoptive transfer. The specifically restimulated immune spleen cells were radiolabeled with [3H]thymidine, 1 X 10(8) viable cells were adoptively transferred in tumor-bearing guinea pigs, and their distribution was investigated. As controls for the specific localization of the immune cells at the line 10 tumor, the presence of labeled cells was studied in the contralateral transplanted line 1 hepatoma as well as in cellular inflammatory reactions elicited by injection with incomplete Freund's adjuvant (IFA) and complete Freund's adjuvant (CFA). A significantly higher localization of the labeled immune spleen cells in the line 10 tumor and the first and second draining lymph nodes of the line 10 challenge site were found when compared to the influx of these cells in the line 1 tumor and the nontumor antigen-related inflammatory reactions. Because our immune donor animals were immunized with a mixture of line 10 cells and BCG, these animals are immune to both. Line 10 immune spleen cells were restimulated in vitro with PPD and were radiolabeled. These PPD-restimulated immune spleen cells showed no preferential localization at the line 10 tumor challenge site but, as expected, a tendency for localization at the CFA (H37Ra) injection site. Furthermore, PPD-reactive spleen cells from BCG-immunized guinea pigs showed a significantly higher accumulation at the CFA injection site compared to the IFA injection site and the line 10 and line 1 tumor challenge site. From the results, it is concluded that line 10 tumor-immune and BCG-immune spleen cells are two distinct cell populations, and that the existence of cross reacting antigens between BCG and the line 10 hepatocarcinoma are of no importance for the rejection of the line 10 tumor by immune spleen cells. PMID- 2578527 TI - Histologic distribution of staining by a monoclonal antibody (psi-3) in psoriasis and occurrence of psi-3 antigen in other cutaneous diseases. AB - psi-3 is a monoclonal antibody that recognizes a 135,000 molecular weight structural component of maturing keratinocytes in psoriasis (the psi-3 antigen) but fails to bind to any constituent of keratinocytes in normal epidermis. This paper describes the occurrence of the psi-3 antigen in a variety of dermatopathologic conditions using immunoperoxidase (biotin-avidin-peroxidase) and immunofluorescence methods which show excellent concordance. In 35 of 36 specimens of psoriasis vulgaris, psi-3 antibody consistently immunolabels the cytoplasm of keratinocytes above the basal layer. At the edges of psoriatic plaques, psi-3 antibody staining extends for a variable distance into lesion-free epidermis. A similar pattern has been found in a certain number of other conditions described in the paper, including squamous cell carcinoma and condyloma acuminatum, but not Darier's disease, basal cell carcinoma, nor lamellar ichthyosis. In all but one condition, the outermost or basal layer of cells is never stained. The only disease in which the lowermost cell layer is stained is a lichen planus-like lesion. The occurrence of psi-3 antigen cannot be correlated with any histologic feature of psoriasis such as acanthosis, loss of the granular layer, or hyperproliferation. The antigen appears to be a unique keratinocyte constituent which is expressed in certain pathologic conditions and which is not detected by any other histologic or immunophenotyping method. It is a potentially valuable addition to the panel of antibodies available for characterizing epithelial cells. PMID- 2578529 TI - Epidermal growth factor stimulates tyrosine phosphorylation of pig epidermal fibrous keratin. AB - Epidermal growth factor (EGF) stimulated phosphorylation of pig epidermal proteins, one of which was pig epidermal keratin. In order to further characterize phosphorylated proteins and specify the EGF-dependent protein phosphorylation, we attempted to identify phosphorylated keratin proteins and to analyze phosphorylated phosphoamino acids of keratin proteins stimulated by EGF. Four major polypeptide bands of pig epidermal keratin were immunoprecipitated by antihuman callus keratin antibody which reacted with fine networks of fibrous keratin of pig epidermal cells grown in vitro. Four major polypeptide bands were greatly phosphorylated by EGF in a dose-dependent manner. The analysis of phosphorylated phosphoamino acids revealed that EGF stimulated tyrosine phosphorylation of pig epidermal fibrous keratin. PMID- 2578528 TI - Immunologic properties of enzymatically degraded human keratin intermediate filaments. AB - In order to gain insight into the metabolism of keratin intermediate filaments (KIF) as well as the ability of KIF degradation products to interact with the immune system, we performed enzymatic degradation of purified KIF and examined their interaction with anti-KIF autoantibodies and their ability to act as immunogens. Aliquots of KIF aggregates were exposed to 3 different enzymes, that is, alpha-chymotrypsin, plasmin, and trypsin, in dose- and time-dependent experiments. The effect of the digestion was monitored sequentially by polyacrylamide gel electrophoresis and simultaneously by transmission electron microscopy. Furthermore, the KIF degradation proteins were then examined for their ability to bind anti-KIF autoantibodies by immunoblot and for their immunogenicity. In addition, preincubation of KIF with anti-KIF autoantibodies prior to the digestion procedure was performed to investigate a possible protective effect of this treatment against proteolytic degradation. The experiments demonstrated that: (1) KIF are degraded by serine proteinases, (2) with prolonged incubation time intact KIF are progressively replaced by more granular-amorphous material in transmission electron microscopy, (3) anti-KIF autoantibodies bind to KIF degradation proteins, (4) preincubation of KIF with anti-KIF autoantibodies does not exert any major protective effect for KIF against proteolytic degradation, and (5) the enzymatic degradation products of KIF can function as effective immunogens causing the formation of high-titer anti KIF antibodies. PMID- 2578530 TI - Antirespiratory and antiproliferative activity of anthralin in cultured human keratinocytes. AB - The effect of anthralin and its oxidation products, anthralin-dimer and anthralin quinone, on protein content and thymidine incorporation as well as CO2 production from glucose and glutamine has been studied in transformed human keratinocytes in vitro. Anthralin exhibited the strongest inhibition, the dimer was generally less active and the quinone inactive. Respiration and thymidine incorporation were the most sensitive cellular functions showing 50% inhibition at about 1 and 3 microM anthralin, respectively. Comparison of the inhibition kinetics of anthralin with those of antimycin A and mitomycin C showed that anthralin behaved as an inhibitor of mitochondrial function rather than of DNA replication. The biologic effects were triggered in the first minutes of exposure to the cells when anthralin became rapidly associated with the cell membranes. Labeling experiments with [14C]anthralin revealed that the manifestation of the biologic response occurring after a latency phase of some hours coincided with the accumulation of radioactivity in the intracellular particulate fraction. The cytosol remained essentially unlabeled. PMID- 2578531 TI - Freeze-fracture cytochemical study of membrane systems in human epidermis using filipin as a probe for cholesterol. AB - Filipin (a polyene antibiotic) interacts specifically with cholesterol in membranes, producing characteristic 25 nm-diameter deformation (pitlike lesions) within the membrane plane detectable by freeze-fracture electron microscopy. Utilizing this probe, the distribution of cholesterol molecules in membranes and in lamellar structures between horny cells was investigated in human skin. The plasma membranes of basal, spinous, and granular cells reacted extensively with filipin except for desmosomal membrane portions. However, the plasma membranes of horny cells were rarely labeled with filipin, while lamellar structures between horny cells were well labeled. These observations indicate the distinct difference in susceptibility to filipin among the plasma membranes of viable cells and horny cells, and the lipid lamellar structures. Whenever horny cell plasma membranes were affected with filipin, they revealed a low deformability showing shallow pits or low protrusions. This low deformability may be due to greater membrane rigidity rather than a lower content of cholesterol, although the possibility of a low amount of cholesterol cannot be excluded. Lamellar bodies in granular cells were well labeled in the limiting membranes but poorly labeled in the internal lamellar structures. The regions of gap junctions were absolutely unlabeled. Filipin-cholesterol complexes were produced very close to the junctional strands but did not appear to disrupt the junctional structure of tight junctions. Nuclear membranes were affected only in the outer membrane with filipin. These results suggest that keratinocytes undergo a distinctive reduction in membrane deformability or in free-cholesterol content at the transition from living to dead cells, and display a heterogeneity in cholesterol distribution in human epidermal cell membranes. PMID- 2578532 TI - Exploitation of phylogenetic distance in cell surface immune labeling: studies with beta 2-microglobulin. AB - Beta 2-microglobulin (beta 2M) is part of the HLA molecule, and is found on the cell surface of human nucleated cells. In certain skin tumors, malignant change has been associated with a loss of this surface beta 2M, indicating a possible diagnostic value for this marker. At present beta 2M is best identified in paraffin-embedded tissue by means of a triple-layer peroxidase-antiperoxidase technique, using mammalian polyclonal antisera. Recently a polyclonal antiserum against human beta 2M has been produced in chickens. Because of the phylogenetic differences between the species, the resulting antiserum is likely to recognize more epitopes on the beta 2M and show greater sensitivity than antisera raised in mammalian species. To confirm this hypothesis, the avian antiserum was compared to both mammalian polyclonal (rabbit) and monoclonal (mouse) antibody in vitro. beta 2M fixed to plastic surfaces combined with more avian than mammalian antibody. Furthermore, insolubilized chicken antibody could bind more secondary antibody-horseradish peroxidase conjugate than could insolubilized mammalian antibody, thus showing even greater enhancement with this system. Immunohistochemical analysis of these systems confirmed that the chicken strategy has greater sensitivity, and can be used in an indirect system with consequent reduction in nonspecific background activity. It is the most suitable technique for the investigation of the distribution of beta 2M in paraffin-embedded tissue. PMID- 2578533 TI - Neuraminidase production by streptococci from patients with glomerulonephritis. AB - Autoantigenic events in acute poststreptococcal glomerulonephritis (APSGN) may result from neuraminidase-induced alterations in immunoglobulin levels. Whether streptococci from patients with APSGN produced neuraminidase and, if so, what substrates could be used for screening purposes and what were of potential clinical relevance were determined. Group A streptococci cultured from 20 patients with APSGN and four patients with acute rheumatic fever and group B, C, D, and G streptococci cultured from other individuals were reacted with the substrates to determine neuraminidase activity by the thiobarbituric acid assay. Neuraminidase production was detected in 16 of 20 streptococci from patients with APSGN. Partial purification by Sephadex G-150 chromatography gave two peaks, and polyacrylamide gel electrophoresis gave two bands with neuraminidase activity. Bovine mucin was the most useful substrate to detect neuraminidase production by nephritogenic streptococci, and with respect to human substrates, IgM was the most sensitive and renal basement membrane the least sensitive to enzyme action. PMID- 2578535 TI - Measurement and management of tinnitus. Part II. Management. PMID- 2578534 TI - Purification of functional RNA from human granulocytes. AB - The presence, in granulocytes, of high levels of nuclease activity makes it difficult to isolate intact RNA from these cells. We have developed a method that allows purification of functional RNA from normal granulocytes as determined by capability for reverse transcription and in vitro translation. We have shown that a considerable amount of ribonuclease activity remains in granulocyte lysates, even after the addition of heparin or vanadyl ribonucleoside complexes. RNA isolated from such lysates demonstrates only minimal binding to oligothymidylic cellulose and does not serve as a template for reverse transcription or in vitro translation. However, the extraction of frozen granulocytes into phenol in the presence of both heparin and vanadyl ribonucleoside allows the purification of relatively large quantities of RNA, which serves as an excellent template for reverse transcription and in vitro translation. Purification of granulocyte RNA by this method will facilitate study of granulocyte gene expression. PMID- 2578536 TI - Evidence that X-irradiation and 4-hydroperoxycyclophosphamide affects different lymphocytes that respond to specific antigen in vitro. AB - The present study examined the effect of pulse treatment with the in vitro active synthetic derivative of cyclophosphamide (CY), 4-hydroperoxycyclophosphamide (4 HPCY), and exposure to X-irradiation on the in vitro Concanavalin A (ConA), lipopolysaccharide (LPS), and antigen-specific blastogenic responses of in vivo primed lymph node cells. Primed lymph node cells from CY-pretreated, aggregated (A) human IgG-complete Freund's adjuvant (AHGG-CFA)-immunized mice were untreated, exposed to various doses of irradiation, or pulse treated with different concentrations of 4-HPCY before being cultured in medium alone or in medium containing HGG, ConA, or LPS. The results show that HGG-responding and LPS responding cells exhibited similar dose-inactivation profiles following exposure to irradiation or pulse treatment with 4-HPCY. More than 75% of reactivity was eliminated by exposure to 100 rads or pulse treatment with 20 microM 4-HPCY. In contrast to preculture pulse treatment with 4-HPCY, however, when primed lymph node cells were cultured in medium containing 4-HPCY (culture treatment) LPS responding cells were shown to be more sensitive to inactivation than HGG responding cells. The data further show that the effect of low-dose irradiation and of culture treatment with 4-HPCY on the HGG-specific response of primed lymph node cells was additive, suggesting that these agents inactivate different cell subtypes that contribute to the HGG-specific response in vitro. PMID- 2578537 TI - Macrophage activation by cross-linked dextran. AB - Cross-linked dextran (Sephadex) has been reported as an effective inducer of peritoneal exudates resulting in a large yield of macrophages after injection into mice, and macrophages obtained in this manner have been used for a variety of studies. We examined the possibility that cross-linked dextran not only induces peritoneal exudate but functions also as a macrophage activator. Following confirmation of a markedly increased yield of macrophages in Balb/c mice injected with preswollen Sephadex G-25 beads, glass adherence and migration in agarose of these macrophages were compared with the activities of cells isolated following the injection of saline, thioglycollate, or complete Freund's adjuvant (CFA). Dextran administration resulted in a significant increase in these activities in relation to saline and thioglycollate injections, and resembled CFA in the magnitude of its effect. Dextran-induced macrophages were then examined for activation as defined by nonspecific antitumor activity. Cells of a transplantable fibrosarcoma line and a urethane-induced primary lung adenoma served as targets. As compared with macrophages isolated from saline-injected mice, cells induced by Sephadex showed an approximately fivefold and twofold increase in activity against adenoma and fibrosarcoma targets, respectively. To examine the ability of Sephadex to induce macrophage antitumor activity in vitro, peritoneal macrophages were cultured in the presence of the dextran for 24 hours and tested against adenoma targets. The tumoricidal/static activity of such macrophages was significantly increased relative to controls and was nearly identical to the activity of macrophages induced by Sephadex in vivo. It is clear that cross-linked dextran in the form of Sephadex G-25 can function both as an inducer of peritoneal exudate and as an effective macrophage activator with regard to the activation criteria studied. PMID- 2578538 TI - Possible roles of calcium and calmodulin in mammary gland differentiation in vitro. AB - In response to insulin, cortisol and prolactin, mammary gland explants from virgin mice will undergo differentiation, as measured by lactose synthetase activity and casein synthesis. W-13 (N-(4-aminobutyl)-5-chloro-2 naphthalenesulphonamide), a calmodulin inhibitor, reduced prolactin-induced differentiation by 80% while inhibiting insulin- and cortisol-induced RNA synthesis only 40%. However, tissue levels of calmodulin did not change during a 3-day culture, with or without prolactin, suggesting that the regulatory component of the calcium-calmodulin system was the intracellular calcium concentration. In support of this hypothesis, verapamil, a calcium channel blocker, also preferentially inhibited prolactin-induced differentiation and prolactin did stimulate calcium accumulation (from a control value of 3.8 +/- 1.3 (S.E.M.) pg calcium/mg wet tissue per 15 min to 61.4 +/- 7.0). On the other hand, A23187, a calcium ionophore which mimicked prolactin actions on calcium accumulation, was not able to induce differentiation in the absence of prolactin; in fact, high concentrations of either A23187 or extracellular calcium actually inhibited lactose synthetase activity, although casein synthesis was relatively unaffected. Therefore, it appears that the calcium-calmodulin system is involved in prolactin-induced differentiation of mammary gland explants but that it cannot be the only mediator of prolactin actions; i.e. it is necessary but not sufficient. There also appears to be another, separate action of calcium on casein synthesis which involves increasing the mammary epithelial sensitivity toward prolactin with respect to casein synthesis but not lactose synthetase activity. PMID- 2578539 TI - Multiple, heart-cross-reactive epitopes of streptococcal M proteins. AB - We present evidence that a highly purified pepsin extract of type 5 streptococcal M protein (pep M5) contains at least three epitopes that are cross-reactive with sarcolemmal membrane proteins of human myocardium. The tissue-cross-reactive determinants of pep M5 are also partially shared with pep M6 and pep M19. Three rabbits immunized with a single 300 micrograms dose of pep M5 developed significant levels of heart-cross-reactive antibodies, as determined by indirect immunofluorescence tests. All three sera also contained antibodies that cross reacted with pep M6 and pep M19. The heart tissue--specific antibodies that were eluted from sarcolemmal membranes opsonized types 5, 6, and 19 streptococci, indicating that they were directed against protective M protein epitopes on the surface of virulent organisms. Immunofluorescence inhibition tests, using purified M proteins as soluble inhibitors of heart-cross-reactive antibodies, revealed the number and M protein serotype distribution of the tissue-cross reactive epitopes. Immunoblot analyses demonstrated the sarcolemmal membrane proteins containing the various cross-reactive antigenic determinants. PMID- 2578540 TI - Polymorphism of a high molecular weight schizont antigen of the human malaria parasite Plasmodium falciparum. AB - Intraspecies antigenic diversity in the blood stages of the human malaria parasite Plasmodium falciparum was investigated using a collection of murine monoclonal antibodies and clones of the parasite. The results were as follows: (a) The schizont and merozoite stages of the parasite express on their surface clonally restricted antigens detectable by strain-specific antibodies in indirect immunofluorescence tests. (b) These restricted antigens are phenotypically stable characteristics of clones grown in vitro. (c) The molecules carrying the specific antigens were isolated by immunoprecipitation and were found to be parasite proteins ranging in size from Mr 190,000 to 200,000 between clones. (d) Comparative immunoprecipitation and peptide mapping of these molecules showed that each parasite clone expresses a protein that is antigenically and structurally distinct from the equivalent products of several other clones. (e) The different clonal products are, however, immunologically interrelated, since they possess determinants in common with all tested isolates of the parasite. (f) These polymorphic molecules are closely related to a previously described schizont protein of P. falciparum that is posttranslationally cleaved into fragments located on the merozoite surface. These findings show the existence of a family of related polymorphic schizont antigens (PSA) of P. falciparum, whose expression is clonally restricted, and indicate that these proteins have regions of constant and variable antigenicity. We propose that a system of immunological classification of the parasite can be developed based on the polymorphism of these proteins. PMID- 2578541 TI - Use of monoclonal antibodies for the characterization of novel DNA-binding proteins recognized by human autoimmune sera. AB - Autoantibodies to a DNA-binding heterodimer consisting of 70,000 and 80,000 dalton subunits were identified in 30-50% of human autoimmune sera from patients with systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and scleroderma. Three murine monoclonal antibodies (mAb) against the heterodimer were produced in BALB/c mice by immunizing with isolated human B cell nuclei. By immunofluorescence, the mAb and autoimmune sera demonstrated both speckled nucleoplasmic staining and diffuse nucleolar staining in all human cell types examined. The nucleoplasmic staining was sensitive to DNase but not RNase pretreatment, while the nucleolar staining was sensitive to RNase but not DNase pretreatment. Biochemical characterization of the 70,000 and 80,000 dalton proteins using the mAb indicated that two forms of the antigen, with different mobilities on sucrose gradients, are present in human B cells. A 10 S form consists of the physically associated 70,000 and 80,000 dalton proteins, while a larger, 10-20 S form probably represents the same two proteins bound to DNA. Binding of the proteins to nucleolar RNA could not be confirmed in biochemical studies. These studies indicate that non-histone, DNA-binding proteins may be more frequently recognized by autoantibodies in SLE, MCTD, and scleroderma than has been previously recognized. Along with previous studies on RNA-binding proteins such as Sm, RNP, Ro, and La, the present findings suggest that nucleic acid-binding proteins, as a class, may be particularly frequent targets of autoimmunity in SLE and related disorders. PMID- 2578542 TI - Immune complexes can trigger specific, T cell-dependent, autoanti-IgG antibody production in mice. AB - Immunization of mice with a combination of passively administered syngeneic IgG (anti-p-azophenylarsonate [anti-Ars]) antibody and a soluble, multivalent form of the antibody's corresponding antigen (Limulus polyphemus hemocyanin conjugated with Ars [Lph-Ars]) resulted in specific autoanti-IgG Fc (rheumatoid factor) production. The response was rapid and only anti-IgG of the IgM isotype is found. Because immunization with either the IgG antibody or the antigen alone did not result in rheumatoid antibody production, immune complexes appear to be the active form of the immunogens. Antibody/antigen ratios that resulted in maximal anti-IgG antibody responses were the same as those required for peak in vitro immunoprecipitation, i.e., equivalence. Previous exposure of the mice to the exogenously supplied antigen was not required for the response. The response to immune complexes is specific because mice immunized with IgG2a-containing complexes produced autoanti-IgG2a, while mice immunized with IgG1-containing complexes produced anti-IgG1 with little reactivity to other IgG isotypes. IgG2a blocked in its complement-fixing capacity was more effective in eliciting the anti-IgG2a response than native IgG2a, suggesting a possible role for the complement system in modulating the anti-IgG2a response. Induction of rheumatoid factor production by immune complexes could be induced in xid mice but not in nu/nu mice, indicating T lymphocyte dependence of the response. In contrast, the B lymphocyte activator lipopolysaccharide was able to elicit vigorous rheumatoid factor production in both nu/nu and normal mice, demonstrating that nu/nu mice contain B cells capable of making the response. Rheumatoid antibody produced in the immune complex- or LPS-induced responses is Fc specific and has relatively low affinity for IgG that is not bound to antigen. PMID- 2578544 TI - Identification of a specific HLA DR2 Ia molecule as a restriction element for measles virus-specific HLA class II-restricted cytotoxic T cell clones. AB - By using a panel of HLA-D-defined subtypes of HLA-DR2 HCL with known beta chain structural variabilities, we have demonstrated that HLA-DR2, OKT4+ cytotoxic T lymphocyte (CTL) clones specific for measles virus are apparently restricted to a distinct DR beta chain. The presence of this DR beta 2 molecule correlated precisely with the susceptibility of measles virus-infected HLA-DR2 HCL to lysis by these CTL clones. These studies demonstrate that delineation of HLA-DR2 into various subgroups can have a functional significance that parallels the structural differences within the HLA-D region. These results are discussed in the context of the possible association of HLA class II-restricted, measles virus specific CTL and multiple sclerosis. PMID- 2578543 TI - Interferon enhances the susceptibility of virus-infected fibroblasts to cytotoxic T cells. AB - Interferon (IFN) pretreatment of low-passage mouse embryonic fibroblasts (MEF) infected with lymphocytic choriomeningitis virus or vaccinia virus rendered these cells two to three times more susceptible to lysis by H-2 restricted, virus specific cytotoxic T lymphocytes (CTL) than control, virus-infected MEF. The increased sensitivity to lysis correlated with increased expression of surface H 2 antigens, but not viral antigens. Continuous cell lines already highly sensitive to CTL-mediated lysis and already expressing high levels of surface H-2 antigens were unaffected by IFN pretreatment. These results suggest that IFN treatment, by increasing surface H-2 levels, may result in increased association of surface H-2 and virus antigens, leading to enhanced recognition and lysis by virus-specific CTL. PMID- 2578545 TI - T cell receptors for responses to Mls determinants and allo-H-2 determinants appear to be encoded on different chromosomes. AB - Previous studies have shown that T cell clones specific for strong Mlsa,d determinants concomitantly display apparently random reactivity to allo-H-2 determinants. One explanation for this finding is that T cell recognition of Mlsa,d and allo-H-2 determinants is controlled by separate sets of receptors. If these receptors were chromosomally unlinked, karyotypically unstable T cell hybrids with dual reactivity for Mlsa,d and particular allo-H-2 determinants would be expected, occasionally, to lose reactivity for one set of determinants, but not the other. The results presented here provide direct support for this prediction. PMID- 2578547 TI - Rheumatoid factor (RF) production during anamnestic immune responses in the mouse. III. Activation of RF precursor cells is induced by their interaction with immune complexes and carrier-specific helper T cells. AB - IgG1 immune complexes were identified as the humoral stimuli responsible for the synthesis of IgG1-specific IgM rheumatoid factor (RF), which occurs in the mouse during the early stages of secondary immune responses to protein antigens. The specificity of this phenomenon was illustrated by the fact that complexes made with IgG1 F(ab')2 fragments or with antibodies of a different isotype failed to induce significant anti-IgG1 RF synthesis. The importance of immune complexes in the induction of RF was further underscored by the substantial increase in the titers of isotype-specific RF observed in the serum of mice immunized with IgG1- or IgG2a-complexed antigen rather than with antigen alone. The RF-inducing capacity of the complexes varied with the antigen/antibody ratio: it was maximal in antibody excess or at equivalence, but dramatically reduced in large antigen excess. The importance of T cell priming in RF precursor cell activation by immune complexes was demonstrated by the failure of T cell-deprived spleen cells to reconstitute the capability of irradiated mice to produce RF, and by the optimal RF responses observed after reconstitution of irradiated recipients with primed T cells and naive B cells. The involvement of T cells in this process could not be explained by the release of nonspecific B cell activators, because antigenic stimulation of primed T cells failed to enhance the activation of RF precursor cells by immune complexes of unrelated antigen. PMID- 2578546 TI - Idiotype connectance in the immune system. II. A heavy chain variable region idiotope that dominates the antibody response to the p-azobenzenearsonate group is a minor idiotope in the response to trinitrophenyl group. AB - We describe the recurrence of a cross-reactive idiotope (CRIAD8) in antibody responses to different epitopes, and explore factors leading to its dominance in some responses, but not others. Serological and genomic DNA analyses showed that CRIAD8 is a marker of the CRIa heavy chain variable region (VH) that encodes the majority of anti-p-azobenzenearsonate (anti-ABA) antibodies. The independence of CRIAD8 from any particular light chain or antigen specificity was underscored by the fact that we could isolate hybridomas that secrete antitrinitrophenyl (TNP) antibodies expressing CRIAD8, with lambda 1 light chains. CRIAD8 is dominant in anti-ABA responses, recurrent but nondominant in anti-TNP and anti-chicken gammaglobulin responses, and is virtually absent in other antihapten responses, including that to p-azobenzenephosphonate (ABP), which contains an ABA-cross reactive component (approximately 5-40%). Dominance in the anti-TNP response could not be achieved by immunization with doubly haptenated TNP-ABA-KLH (keyhole limpet hemocyanin), where the anti-ABA response was dominated by CRIAD8. These observations suggest that, while the CRIAD8 VH region is necessary for idiotypic dominance, it is not sufficient. Apparently, an additional specificity is required. Since immunization with ABA calls up anti-ABP antibodies that express CRIAD8, but not vice versa, it is possible that the additional specificity is ABA itself. This possibility imposes a new constraint on the specificity of the putative idiotype-specific regulation that may establish dominance in the CRIa system. PMID- 2578550 TI - Studies on the herpes simplex virus alkaline nuclease: detection of type-common and type-specific epitopes on the enzyme. AB - Five monoclonal antibodies to the alkaline nuclease of herpes simplex virus (HSV) types 1 and 2 have been used in immunoperoxidase tests to demonstrate the nuclear localization of the enzyme within HSV-1- and HSV-2-infected cells and to purify the enzyme from cells infected with either virus by immunoadsorbant chromatography. Affinity chromatography with a 32P-labelled extract of HSV-2 infected cells has enabled us to demonstrate that the nuclease eluting from the immunoadsorbant is a phosphoprotein, hence confirming the nuclease to be identical to the phosphorylated polypeptide previously referred to as ICSP 22 (HSV-2) or ICP 19 (HSV-1). In addition, the results clearly demonstrate that monoclonal antibodies Q1, CC1 and CH2 are directed against HSV type-common epitopes while V1 and T2T1 antibodies are against HSV-2-specific epitopes on the enzyme. Using the type-specific monoclonal antibodies in an immunoperoxidase test, the enzyme specified in cells infected with intertypic recombinants has been typed; correlation of these data with restriction endonuclease maps of the recombinants has enabled us to map the position of the active site of the nuclease gene to map units 0.168 to 0.184 on the genomes of both HSV-1 and HSV-2. Taken with the data mapping the mRNA encoding this enzyme, the nuclease active site can be mapped to 0.168 to 0.175 on the genome. Finally, the use of monoclonal antibodies in immunofluorescence tests on infected cells has demonstrated that the nuclease is synthesized within 2 h post-infection. PMID- 2578548 TI - Temperature effects on sodium pump phosphoenzyme distribution in human red blood cells. AB - Phosphorylation of red cell membranes at ambient temperatures with micromolar [32P]ATP in the presence of Na ions produced phosphoenzyme that was dephosphorylated rapidly upon the addition of ADP or K ions. However, as first observed by Blostein (1968, J. Biol. Chem., 243:1957), the phosphoenzyme formed at 0 degrees C under otherwise identical conditions was insensitive to the addition of K ions but was dephosphorylated rapidly by ADP. This suggested that the conformational transition from ADP-sensitive, K-insensitive Na pump phosphoenzyme (E1 approximately P) to K-sensitive, ADP-insensitive phosphoenzyme (E2P) is blocked at 0 degrees C. Since the ATP:ADP exchange reaction is a partial reaction of the overall enzyme cycle dependent upon the steady state level of E1 approximately P that is regulated by [Na], we examined the effects of temperature on the curve relating [Na] to ouabain-sensitive ATP:ADP exchange. The characteristic triphasic curve seen at higher temperatures when [Na] was between 0.5 and 100 mM was not obtained at 0 degrees C. Simple saturation was observed instead with a K0.5 for Na of approximately 1 mM. The effect of increasing temperature on the ATP:ADP exchange at fixed (150 mM) Na was compared with the effect of increasing temperature on (Na + K)-ATPase activity of the same membrane preparation. It was observed that (a) at 0 degrees C, there was significant ouabain-sensitive ATP:ADP exchange activity, (b) at 0 degrees C, ouabain sensitive (Na + K)-ATPase activity was virtually absent, and (c) in the temperature range 5-37 degrees C, there was an approximately 300-fold increase in (Na + K)-ATPase activity with only a 9-fold increase in the ATP:ADP exchange. These observations are in keeping with the suggestion that the E1 approximately P ---E2P transition of the Na pump in human red cell membranes is blocked at 0 degrees C. Previous work has shown that the inhibitory effect of Na ions and the low-affinity stimulation by Na of the rate of ATP:ADP exchange occur at the extracellular surface of the Na pump. The absence of both of these effects at 0 degrees C, where E1 approximately P is maximal, supports the idea that external Na acts through sites on the E2P form of the phosphoenzyme. PMID- 2578549 TI - Sodium channel activation in the squid giant axon. Steady state properties. AB - Treatment of giant axons from the squid, Loligo pealei, with pronase removes Na channel inactivation. It was found that the peak Na current is increased, but the activation kinetics are not significantly altered, by pronase. Measurements of the fraction of open channels as a function of voltage (F-V) showed an e-folding at 7 mV and a center point near -15 mV. The rate of e-folding implies that a minimum of 4 e-/channel must cross the membrane field to open the channel. The charge vs. voltage (Q-V) curve measured in a pronase-treated axon is not significantly different from that measured when inactivation is intact: approximately 1,850 e-/micron2 were measured over the voltage range -150 to 50 mV, and the center point was near -30 mV. Normalizing these two curves (F-V and Q V) and plotting them together reveals that they cross when inactivation is intact but saturate together when inactivation is removed. This illustrates the error one makes when measuring peak conductance with intact inactivation and interpreting that to be the fraction of open channels. A model is described that was used to interpret these results. In the model, we propose that inactivation must be slightly voltage dependent and that an interaction occurs between the inactivating particle and the gating charge. A linear sequence of seven states (a single open state with six closed states) is sufficient to describe the data presented here for Na channel activation in pronase-treated axons. PMID- 2578551 TI - Preliminary characterization of a persistent infection of HeLa cells with human rhinovirus type 2. AB - We were able to initiate a persistent infection (PI) in HeLa cells with a temperature-sensitive (ts-) mutant of rhinovirus type 2 (TS-1), but not with the corresponding wildtype (wt) virus. The ability to initiate a PI may be related to the multiplicity of infection. Persistence was established at 37 degrees C but not at 32 degrees C and the virus isolated from the PI was no longer temperature sensitive. Infectious virus was continually produced at low levels throughout the course of the PI and cell cultures underwent multiple episodes of partial destruction (crisis) and subsequent recovery. PI virus and the initiating virus were neutralized to the same extent by hyperimmune polyclonal TS-1 antiserum indicating that no significant change had occurred with respect to serological type. The presence of either interferon or virus-related interfering activity could not be demonstrated in the PI cultures. Superinfection experiments in cells that were 'cured' of PI virus indicated the selection of a cell population during persistence that could no longer support the growth of homologous-type virus. This effect became less pronounced upon further passage of the cured cells. When compared with the wt and ts viruses, the PI virus yielded comparable amounts of infectious virus in HeLa cells but with decreased synthesis of RNA. PMID- 2578552 TI - Stabilization by host cell components and Mg2+ of the neutralization epitopes of poliovirus. AB - When type 1 poliovirions were extracted from infected HeLa cells and heated at 56 degrees C in the presence of 1 mM-Mg2+, RNA-free, pluri-antigenic particles were formed. These particles possessed neutralization epitopes as well as epitopes associated with H antigen and with the isolated capsid protein VP3. The heating caused the formation of exclusively H antigenic particles when the Mg2+ concentration was 10(-4) M or lower, or when the virus was further purified in order to remove remaining cellular components. The ability of purified virus to form pluri-antigenic particles upon heating could be restored by incubation at 37 degrees C with infected cell extract. PMID- 2578553 TI - In vitro cleavage of Pr65gag by the Moloney murine leukaemia virus proteolytic activity yields p30 whose NH2-terminal sequence is identical to virion p30. AB - In vitro cleavage of Gazdar murine sarcoma virus Pr65gag, which has all of the antigenic determinants of Moloney murine leukaemia virus Pr65gag, i.e. p15, p12, p30 and p10, by the Moloney murine leukaemia virus proteolytic activity yielded a p30 whose partial NH2-terminal sequence was identical to Moloney murine leukaemia virus. Both [3H]leucine-labelled and unlabelled Pr65gag were used to generate the cleaved p30. PMID- 2578554 TI - How useful are serum and CSF interferon levels as a rapid diagnostic aid in virus infections? AB - Specimens from a total of 162 patients were studied prospectively using a rapid nucleic acid synthesis inhibition assay and a plaque-reduction assay to detect interferon levels in serum and cerebrospinal fluid. The specificity, consistency, and diagnostic applications of the rapid assay were evaluated by intensively investigating each patient for possible viral illness. Forty-one percent of patients with proven acute virus infections (excluding those with acute hepatitis and infectious mononucleosis) had unequivocal detectable interferon in serum or cerebrospinal fluid, compared with only two patients with bacterial infections (7%) who had equivocal interferon in the serum. Retrospective analysis showed the test to have high specificity for virus infections, but in patients with clinical syndromes of uncertain aetiology the test was not a particularly sensitive indicator of the presence of subsequently detected virus. The presence of interferon was not related to the time during the illness at which the sample was taken, nor to the numbers of lymphocytes in the cerebrospinal fluid, nor to the patients' general symptoms. PMID- 2578556 TI - Chronic myelogenous leukemia: is aggressive treatment indicated? PMID- 2578555 TI - Suicidal fantasies in normal children. AB - This study of a randomly selected sample of 101 schoolchildren, who had no history of previous psychiatric symptomatology, showed that approximately 12% of the children had suicidal impulses. Verbatim statements of the children about their suicidal tendencies are presented. Case vignettes illustrate the common occurrence of parental depression and suicidal behavior and the child's identification with these depressed parents. Clinical implications of these findings are discussed. PMID- 2578557 TI - Tamoxifen flare in advanced endometrial carcinoma. AB - Tamoxifen citrate has recently been shown to be effective palliative therapy in advanced endometrial carcinoma. Flare reactions from tamoxifen are well known in treatment of metastatic breast carcinoma and are not an indication for stopping therapy. We report a patient being treated with tamoxifen for advanced endometrial cancer who developed acute abdominal pain as a manifestation of a flare reaction and the significance of this observation. PMID- 2578559 TI - Loss of tissues in female rats subjected to food restriction during lactation or during both gestation and lactation. AB - The effects of food restriction (50% of ad libitum-fed controls) on maternal tissues during lactation (LR) or during both gestation and lactation (GLR) were examined in rats. Skeletal muscle protein, RNA and fiber diameter were reduced in response to the LR and GLR treatments, but muscle DNA and fiber number were unchanged. Mean body weights of the pregnant (GLR) and nonpregnant female rats were not significantly different after the first 3 wk of food restriction (after delivery in pregnant GLR rats). Compared to the controls, pups of the GLR females had a significantly smaller mean birth weight. The LR females lost weight and catabolized fat pads, organs, and skeletal muscles while nonlactating females gained weight when given a similar amount of food. These results indicated that the demands of gestation did not significantly add to the loss of maternal body weight due to the restriction of food intake. However, the demands of lactation caused the food-restricted females to catabolize significant amounts of maternal tissues. PMID- 2578560 TI - Fibrin degradation and angiogenesis: quantitative analysis of the angiogenic response in the chick chorioallantoic membrane. AB - Fibrin deposition and removal is a feature common to major pathological processes such as wound healing, chronic inflammation and tumour invasion: processes involving the ingrowth of new blood vessels. Low molecular weight fibrin degradation products (MW less than 50,000) are now shown to induce angiogenesis in the chick chorioallantoic membrane (CAM). This effect has also been shown by new quantitative assays to be associated with stimulation of both DNA and protein synthesis. Autoradiography indicates that all cell types in the CAM are stimulated to divide, and it is proposed that fibrin degradation products are a pathological growth factor. PMID- 2578558 TI - Transplantation of adrenal medullary tissue to striatum in parkinsonism. First clinical trials. AB - Autologous adrenal medullary tissue was transplanted to the striatum in two patients with severe parkinsonism. The aim was to provide the striatum with a new cellular source of catecholamines. Some rewarding effects were registered. This is the first time that such tissue has been transplanted in the human brain. The results merit further clinical trials. PMID- 2578561 TI - Ultrastructural and immunohistochemical features of lobular carcinoma of the breast. AB - Twenty cases of infiltrating lobular carcinoma (12 of classical type, five of trabecular type and three of alveolar type) and one case of lobular carcinoma in situ were studied by transmission electron microscopy. The in situ component in three of the infiltrating carcinomas was also studied. The ultrastructure of the tumour cells in the alveolar variant of infiltrating lobular carcinoma was the same as seen in the tumour cells of lobular carcinoma in situ. The tumour cells in infiltrating lobular carcinoma of the classical and trabecular types had more irregular nuclei and were more organelle- and filament-rich. Immunohistochemical staining for the presence of alpha-lactalbumin was proved in 19 per cent of the cases, casein 81 per cent, CEA in 65 per cent and prekeratin in 90 per cent. The light microscopic separation of some subgroups of infiltrating lobular carcinoma may be difficult, in particular the distinction between the classical and the trabecular variants. Unfortunately, our study shows that these distinctions cannot easily be made either by electron microscopy or by light microscopic immunohistochemistry with antibodies against prekeratin, CEA, casein and alpha lactalbumin. PMID- 2578562 TI - Mechanism by which serotonin attenuates contractile response of canine mesenteric arterial smooth muscle. AB - We investigated the mechanism by which prior exposure to serotonin (5-HT) attenuates contractile response to norepinephrine (NE) in dog mesenteric artery. Helically cut strips from dog mesenteric artery were mounted in muscle baths for isometric force recording. Prior treatment with 5-HT (10(-8) to 2 X 10(-7) M) attenuated the response to 2.5 X 10(-7) M NE by 26 to 61%. The attenuation lasted approximately 30 min. The attenuation is not affected by adrenergic denervation, endothelial removal, propranolol, indomethacin or arachidonate. Prior treatment with 5-HT also attenuated responses to: methoxamine, clonidine, prostaglandin F2 alpha, KCl and 5-HT itself. Inhibition of sodium influx by amiloride or inhibition of the electrogenic pump by ouabain diminished the NE attenuation. Verapamil, a calcium channel blocker, diminished the attenuation by 5-HT whereas ryanodine, an intracellular calcium release blocker, had no effect. Prior treatment with 5-HT caused a reduction in the 45Ca influx stimulated by NE. Ketanserin, a 5-HT blocker, exaggerated the attenuation of the NE response caused by 5-HT. Methysergide and cyproheptadine, also 5-HT blockers, diminished the attenuation. These results are compatible with the following interpretation: 1) 5 HT attenuates both receptor- and nonreceptor-mediated contractions of vascular smooth muscle; 2) this attenuation is the result of an increased sodium influx that stimulates the electrogenic sodium pump to cause membrane hyperpolarization and decreased stimulated calcium influx; and 3) the effects of 5-HT are mediated by 5-HT receptors that are blocked by methysergide and cyproheptadine but not by ketanserin. PMID- 2578563 TI - Propranolol-induced elevation of pulmonary collagen. AB - Current concepts of collagen metabolism suggest that fibroblasts tightly control collagen production. One of the possible mechanisms of control is via the cyclic nucleotides, cyclic AMP (cAMP) and cyclic GMP (cGMP). Beta adrenergic agonists, by elevating intracellular cAMP levels, have been shown in vitro to suppress fibroblast collagen production; whereas beta adrenergic antagonists were effective in removing this suppression by blocking the rise in cAMP. In the present study with mice, we showed that administration of the beta adrenergic antagonist, propranolol, at a dose demonstrated to decrease the ratio of cAMP to cGMP, resulted in an elevation in total lung collagen in vivo. The increase in collagen was evident only when propranolol was administered before and during acute lung damage induced by either butylated hydroxytoluene, bleomycin or high concentrations of oxygen. There was no increase in lung collagen when propranolol administration was delayed after injury or when given to an undamaged lung. We propose that via beta adrenergic blockade by propranolol, fibroblasts involved in the normal reparative process may have lost a mechanism for regulatory control, resulting in excessive deposition of collagen. PMID- 2578564 TI - Effects of ethanol and other intoxicant-anesthetics on voltage-dependent sodium channels of brain synaptosomes. AB - Ethanol, diethylether, halothane and enflurane inhibited the veratridine dependent uptake of 24Na by synaptosomes isolated from rodent brain. The inhibitory action of ethanol was similar for uptake periods of 1 to 10 sec and also was observed with batrachotoxin-stimulated sodium uptake, demonstrating an inhibition of sodium influx through voltage-dependent channels. The inhibitory action of tetrodotoxin on sodium uptake was not altered by ethanol, indicating this site on the sodium channel was not altered by ethanol. The action of ethanol was selective for different brain regions and was more potent in inhibiting sodium uptake in cortex than in cerebellum. Investigation of the effects of temperature on veratridine-stimulated uptake and ethanol actions demonstrated that an increase in temperature (13 degrees-33 degrees C) decreased both the apparent KD of veratridine and the Vmax of the uptake. Ethanol decreased the apparent Vmax at all temperatures and decreased the apparent KD at low 13 degrees and 18 degrees C) but not at higher (30 degrees and 33 degrees C) temperatures. Thus, an increase in temperature mimicked some, but not all, of the effects of ethanol. These results, together with those from other studies, suggest that the disordering of membrane lipids by ethanol and other intoxicant-anesthetic drugs is an important factor in the inhibition of sodium channel function by these drugs. PMID- 2578565 TI - Actions of ethanol on voltage-sensitive sodium channels: effects on neurotoxin stimulated sodium uptake in synaptosomes. AB - Exposure of rat brain synaptosomes to ethanol in vitro reduced the neurotoxin stimulated uptake of 22Na+. This effect of ethanol was concentration-dependent, occurred with concentrations of ethanol achieved in vivo and was fully reversible. The inhibitory effect of ethanol on neurotoxin-stimulated sodium uptake was due to a decrease in the maximal effect of the neurotoxins. Ethanol reduced the rate of batrachotoxin-stimulated sodium uptake when measured at 3, 5 and 7 but not 10 or 20 sec after the addition of 22Na+. In a series of aliphatic alcohols, there was a good correlation between potency for inhibition of batrachotoxin-stimulated 22Na+ uptake and the membrane/buffer partition coefficient, suggesting that a hydrophobic site in the membrane was involved in the action of the alcohols. Ethanol did not affect the scorpion venom-induced enhancement of batrachotoxin-stimulated sodium uptake. The inhibitory potency of tetrodotoxin was also unaffected by ethanol. These results demonstrate that ethanol has an inhibitory effect on neurotoxin-stimulated sodium influx occurring in voltage-sensitive sodium channels of brain tissue. PMID- 2578566 TI - Electrophysiologic effects of amiloride in canine Purkinje fibers: evidence for a delayed effect on repolarization. AB - Amiloride, a potassium-sparing diuretic, inhibits Na+ transport, Na+-H+ exchange and possibly Na+-Ca++ exchange in a variety of cellular and epithelial tissues. Similar membrane ion transport mechanisms exist in cardiac tissue, yet there are little data on possible interference by amiloride with ion transport in the heart. Given recent evidence for a delay in amiloride uptake into erythroid cells, we studied the electrophysiologic effects of amiloride after prolonged drug exposure in canine Purkinje fibers using standard microelectrode techniques. Amiloride (1-10 microM) led to a progressive lengthening of action potential duration with a tau of 1.8 +/- 0.5 hr (n = 15). At long cycle lengths (greater than or equal to 2000 msec) early afterdepolarizations and oscillations around the plateau were seen. To determine the etiology of the afterdepolarizations, Purkinje fibers treated for 2 hr with 10 microM amiloride were then exposed to tetrodotoxin, manganese and nisoldipine. Tetrodotoxin (7.8 X 10(-7) M) reversed completely all amiloride effects rapidly and reversibly. MnCl2 (4 mM) increased the afterdepolarizations, and arrest occurred at the plateau potential routinely. Nisoldipine (10(-6) M), a more selective blocker of slow inward current, shortened action potential duration somewhat but did not reverse fully the effects of amiloride. We conclude that amiloride has a pronounced effect on repolarization in the canine Purkinje fiber and this effect is manifest only after prolonged exposure to the drug. PMID- 2578567 TI - delta 9-Tetrahydrocannabinol decreases turnover of brain histamine. AB - Histamine (HA) is a neurotransmitter present in the brain. As there is little information on the effect of delta 9-tetrahydrocannabinol (delta 9-THC) on brain histaminergic activity, the possible delta 9-THC-induced changes in brain HA turnover were studied in rats and mice. Whereas various doses of delta 9-THC had no influence on the brain HA levels in these species, high doses of delta 9-THC reduced the content of tele-methylhistamine (t-MH), a predominant HA metabolite in the brain, in mice. A moderate dose of delta 9-THC was effective in decreasing the brain t-MH content in the rats. Pargyline (65 mg/kg i.p.) caused a 101 ng/g accumulation of t-MH in mice and an 80 ng/g accumulation of t-MH in rats 105 min after the injection. delta 9-THC significantly suppressed the pargyline-induced t MH accumulation at 50 mg/kg in mice whereas only 2 mg/kg of this compound was effective in rats, when administered i.v. 15 min after pargyline treatment. delta 9-THC (50 mg/kg i.v.) delayed the depletion of neuronal HA in the mouse brain, as induced by treatment with a specific histidine decarboxylase inhibitor alpha fluoromethylhistidine (50 mg/kg i.p.). delta 9-THC (30 and 100 microM) significantly inhibited the K+-induced release of endogenous HA from guinea-pig hypothalamic slices. These results suggest that delta 9-THC decreases HA turnover in the brain. PMID- 2578569 TI - Specificity of antibodies for T sites and F sites of streptolysin O. AB - Antistreptolysin antibody (ASO) inhibits haemolysis of erythrocytes coated with streptolysin O (SLO), but antistreptolysin activity may also be due to the presence in sera of peptide fragments of altered beta lipoproteins. SLO-mediated haemolysis results from activity of a molecular site (the t site) distinct from that at which the SLO becomes attached to the cell (the f site), and both sites might be expected to function antigenically. Absorption studies with SLO-coated latex particles, and with SLO-coated erythrocytes in the cold, provide evidence for the existence of both classes of antibody. Results also suggest explanations for the frequent observation of false-negative and false-positive latex tests. PMID- 2578568 TI - Dual effects of dynorphin-(1-13) on cholinergic and substance P-ergic transmissions in the rabbit iris sphincter muscle. AB - In the rabbit iris sphincter muscle, transmural electrical stimulation produces cholinergic and substance P-ergic responses. In the present work, the effects of dynorphin-(1-13), an endogenous ligand of the kappa opioid receptor, on these two neurogenic responses were examined pharmacologically and the data compared to findings in case of other opioid agonists. Dynorphin-(1-13) (10(-7) to 10(-6) M) enhanced the cholinergic responses and attenuated the substance P-ergic response, in a concentration-dependent manner, and these actions of dynorphin-(1-13) were more apparent in the case of low-frequency stimulation. These effects of dynorphin-(1-13) were antagonized by naloxone (10(-5) M). Dynorphin-(1-13) had no effects on the responses to exogenously applied acetylcholine, carbachol and substance P. The augmenting effect on the cholinergic transmission was unique in kappa agonists, as the cholinergic responses were also augmented by other kappa agonists such as dynorphin-(1-17) and ethylketocyclazocine, but attenuated by other opioid agonists (Met-enkephalin, beta-endorphin and morphine) and not affected by SKF-10,047 and nalorphine. On the other hand, the substance P-ergic response was attenuated by all the opioids used. These results suggest that dynorphin-(1-13) presynaptically increases the release of acetylcholine from the parasympathetic postganglionic nerves and reduces the release of substance P from the trigeminal nerve, mediated by kappa type of opioid receptors. PMID- 2578571 TI - Reverse transcription of retroviral genomes: mutations in the terminal repeat sequences. AB - The process of reverse transcription of retroviral genomes begins with the synthesis of a short DNA molecule near the 5' end of the RNA template. This molecule, termed minus-strand strong-stop DNA, is then translocated to the 3' end of the viral RNA by means of a repeated sequence, the R region, present at both ends of the template. The translocation should result in the transfer of genetic information from the 5' R region to the 3' R region. We have generated a series of mutants of Moloney murine leukemia virus with alterations in the R regions by in vitro mutagenesis of a cloned DNA copy of the viral genome. The altered DNAs were introduced into mouse cells by transfection, and the translocation of the mutations during viral replication was assessed. Some mutations were not transferred from the 5' R region to the 3' R region; these results were not in accord with current models for reverse transcription. The results can be explained if DNA molecules shorter than strong-stop DNA, formed by premature termination of synthesis, are sometimes translocated. A number of mutants with large deletions in the R region were tested and were able to replicate with normal strong-stop DNA translocation. Thus, short stretches of homology can be used by the virus to carry out strong-stop translocations. PMID- 2578570 TI - Bacteriophage T4 unf (=alc) gene function is required for late replication in the presence of plasmid pR386. AB - The bacteriophage T4 unf gene, known to be involved in the arrest of transcription from cytosine-containing DNA, is unessential except in Escherichia coli strains containing plasmid pR386. Comparative genetic and biochemical analyses of parameters of unf+ and unf- phage growth in host cells isogenic except for the presence or absence of plasmid pR386 have shown that unf gene function is required for late phage DNA synthesis in the presence of the plasmid. Shutoff of host DNA, RNA, and protein syntheses, degradation of host DNA, adsorption, injection, and early phage DNA, RNA, and protein syntheses all occurred with normal or near-normal kinetics in unf- infections, even in the presence of the plasmid. The switch from early to late protein synthesis occurred in plasmid pR386-containing cells infected with unf+ or unf- phage. However, this switchover was slow in both cases and may be slower in unf- infections than in unf+ infections. Net incorporation of [3H]thymidine terminated at about 30 min after infection of pR386-containing cells with unf- phage at 30 degrees C. Alkaline sucrose gradient studies of the intracellular pools of replicative DNA in unf-infected plasmid pR386-containing cells indicated that this DNA is not detectably nickel or cleaved at the time that DNA synthesis aborts. The addition of chloramphenicol subsequent to early enzyme synthesis prevented the arrest of DNA synthesis in plasmid-containing cells infected with unf-phage. PMID- 2578573 TI - DNA-binding protein associated with herpes simplex virus DNA polymerase. AB - Purified preparations of herpes simplex virus type 2 DNA polymerase made by many different laboratories always contain at least two polypeptides. The major one, of about 150,000 molecular weight, has been associated with the polymerase activity. The second protein, of about 54,000 molecular weight, which we previously designated ICSP 34, 35, has now been purified. The purified protein has been used to prepare antisera (both polyclonal rabbit serum and monoclonal antibodies). These reagents have been used to characterize the protein, to demonstrate its quite distinct map location from that of the DNA polymerase on the herpes simplex virus genome, and to demonstrate the close association between the two polypeptides. PMID- 2578572 TI - Treatment of mice with polyinosinic-polycytidilic polyribonucleotide reduces T cell involvement in a localized inflammatory response to vaccinia virus challenge. AB - Mice inoculated intracerebrally with 10(3) PFU of vaccinia virus developed a nonfatal meningitis which was maximal 7 days after challenge. Intravenous administration of an interferon (IFN) inducer, polyinosinic-polycytidilic polyribonucleotide [poly(I)-poly(C)], on days 4 and 6 postinjection was associated with a three- to fourfold decrease in the number of T lymphocytes present in cerebrospinal fluid, reflected primarily by a decreased number of vaccinia virus-specific cytotoxic T-lymphocyte precursors. The lack of a concomitant reduction in the overall cytotoxic activity of cerebrospinal fluid cells directed against virus-infected target cells seemed to be largely due to an increase in natural killer cell activity. IFN was implicated as mediating the effect of poly(I)-poly(C) because high systemic levels of IFN were evident after injection, and neither the magnitude of the inflammatory response nor the T-cell levels were affected when poly(I)-poly(C)-treated mice were also given anti-IFN antiserum. However, the poly(I)-poly(C)-induced IFN did not seem to reduce the localized inflammatory response by affecting viral replication in brain tissue because the vaccinia virus titers present on days 6 through 8 of infection were similar to the titers in phosphate-buffered saline controls. These findings are consistent with either an effect of IFN on T-cell recruitment to the central nervous system or an inhibition of proliferation of cells participating in the response. These findings suggest that there is a potential source of complications for clinical protocols that use IFN or inducers to enhance T-cell function in various disease situations, and this effect of IFN may be a contributing factor to the immunosuppression often associated with many viral infections. PMID- 2578574 TI - MC29 virus-coded protein occurs as monomers and dimers in transformed cells. AB - The MC29 virus-coded protein p110gag-myc was found exclusively in the nucleus of transformed Japanese quail (Q8) cells, and time course experiments indicated that the protein had a half-life of about 30 min. When extracts of either Q8 or chicken embryo cells infected with MC29 virus were prepared with nondenaturing detergents and then sedimented in sucrose gradients, p110 was found in the fractions expected to contain monomers (5.9S), dimers (9.3S), or mixtures of the two. The same extracts treated with denaturing detergent (0.2% sodium dodecyl sulfate) exhibited p110 only in fractions expected for the monomeric protein, but beta-mercaptoethanol had no effect on the original distribution. Gradients prepared with 0.5 or 1.0 M NaCl failed to dissociate the faster-sedimenting form. No other protein or polyribonucleotide which could increase the sedimentation rate of p110 was found, and neither RNase nor DNase altered the sedimentation pattern of p110 in nondenatured extracts. A reassociation of monomeric p110 into dimers discernible by gel electrophoresis was demonstrated. PMID- 2578575 TI - HBc and HBe antigenicity and DNA-binding activity of major core protein P22 in hepatitis B virus core particles isolated from the cytoplasm of human liver cells. AB - Highly purified hepatitis B virus core particles were obtained in large amounts from the cytoplasm of infected human liver cells. This DNA polymerase-negative core preparation had only hepatitis B core antigen-specific antigenicity and showed a surprising stability. Two forms of a single protein of 22,000 molecular weight, P22, were resolved electrophoretically; the slower moving species, P22a, appeared to be a reduced form of the protein, and the faster moving species, P22b, could have represented a conformational isomer containing an intramolecular disulfide bond(s). The immunological properties and DNA-binding activity of the reduced form, P22a, were examined following separation by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by transfer onto nitrocellulose membranes (Western blotting). We found that the hepatitis B virus C gene protein shared the antigenic site responsible for both hepatitis B core and e antigen reactivity. We also demonstrated that the core protein(s) bound specifically the genomic hepatitis B virus DNA in comparison with a plasmid DNA (pBR322). This last observation was further substantiated by a radioimmunological method. P22a was also found to be phosphorylated in vitro by the endogenous protein kinase activity, copurified with the hepatitis B core antigen particles. These findings suggest that P22 is a multifunctional protein which is incorporated into core particles within the cytoplasm of the host cell before DNA encapsidation. A critical role of this protein in hepatitis B virus assembly is suggested. PMID- 2578578 TI - Neutralizing monoclonal antibodies to Theiler's murine encephalomyelitis viruses. AB - Theiler's murine encephalomyelitis viruses (TMEV) are serologically related picornaviruses which cause both enteric and neurological disease in mice. The biological activities of TMEV vary between the two different TMEV subgroups (TO and GDVII) and with different passage histories of the same TMEV strain (e.g., mouse brain-passed versus tissue culture-passed DA strain of the TO subgroup). We raised neutralizing monoclonal antibodies (mAbs) against tissue culture-passed DA and GDVII strains of TMEV. We produced two mAbs against the DA strain which neutralized all members of the TO subgroup, but not the GDVII subgroup strains (GDVII and FA); these two DA mAbs reacted similarly with both mouse brain-passed DA and tissue culture-passed DA. Of six neutralizing GDVII mAbs, four reacted only to GDVII and FA, whereas two neutralized TO strains as well. These mAbs demonstrate the presence of TMEV group-specific as well as subgroup-specific neutralization and substantiate the division of TMEV into two distinct subgroups. On Western immunoblots one of the two DA mAbs reacted against isolated DA VP1, two GDVII mAbs (which were TMEV group specific) reacted against isolated GDVII VP1 and DA VP1, and the other DA mAb and four other GDVII mAbs required an intact virion conformation for reactivity. An analysis of the epitopes recognized by these mAbs may elucidate sites important in TMEV biological activities. PMID- 2578576 TI - Small and middle T antigens contribute to lytic and abortive polyomavirus infection. AB - Using three different polyomavirus hr-t mutants and two polyomavirus mlT mutants, we studied induction of S-phase by mutants and wild-type virus in quiescent mouse kidney cells, mouse 3T6 cells, and FR 3T3 cells. At different times after infection, we measured the proportion of T-antigen-positive cells, the incorporation of [3H]thymidine, the proportion of DNA-synthesizing cells, and the increase in total DNA, RNA, and protein content of the cultures. In permissive mouse cells, we also determined the amount of viral DNA and the proportion of viral capsid-producing cells. In polyomavirus hr-t mutant-infected cultures, onset of host DNA replication was delayed by several hours, and a smaller proportion of T-antigen-positive cells entered S-phase than in wild-type-infected cultures. Of the two polyomavirus mlT mutants studied, dl-23 behaved similarly to wild-type virus in many, but not all, parameters tested. The poorly replicating but well-transforming mutant dl-8 was able to induce S-phase, and (in permissive cells) progeny virus production, in only about one-third of the T-antigen positive cells. From our experiments, we conclude that mutations affecting small and middle T-antigen cause a reduction in the proportion of cells responding to virus infection and a prolongation of the early phase, i.e., the period before cells enter S-phase. In hr-t mutant-infected mouse 3T6 cells, production of viral DNA was less than 10% of that in wild-type-infected cultures; low hr-t progeny production in 3T6 cells was therefore largely due to poor viral DNA replication. PMID- 2578577 TI - Localization of epitopes of herpes simplex virus type 1 glycoprotein D. AB - We previously defined eight groups of monoclonal antibodies which react with distinct epitopes of herpes simplex virus glycoprotein D (gD). One of these, group VII antibody, was shown to react with a type-common continuous epitope within residues 11 to 19 of the mature glycoprotein (residues 36 to 44 of the predicted sequence of gD). In the current investigation, we have localized the sites of binding of two additional antibody groups which recognize continuous epitopes of gD. The use of truncated forms of gD as well as computer predictions of secondary structure and hydrophilicity were instrumental in locating these epitopes and choosing synthetic peptides to mimic their reactivity. Group II antibodies, which are type common, react with an epitope within residues 268 to 287 of the mature glycoprotein (residues 293 to 312 of the predicted sequence). Group V antibodies, which are gD-1 specific, react with an epitope within residues 340 to 356 of the mature protein (residues 365 to 381 of the predicted sequence). Four additional groups of monoclonal antibodies appear to react with discontinuous epitopes of gD-1, since the reactivity of these antibodies was lost when the glycoprotein was denatured by reduction and alkylation. Truncated forms of gD were used to localize these four epitopes to the first 260 amino acids of the mature protein. Competition experiments were used to assess the relative positions of binding of various pairs of monoclonal antibodies. In several cases, when one antibody was bound, there was no interference with the binding of an antibody from another group, indicating that the epitopes were distinct. However, in other cases, there was competition, indicating that these epitopes might share some common amino acids. PMID- 2578580 TI - Vesicoureteral reflux in patients with obstructive prostatic disease. AB - We present our experience during a 22-year period with the management of 53 patients in whom vesicoureteral reflux was associated with obstructive prostatic disease. There were 45 cases of benign prostatic hyperplasia and 8 cases of carcinoma of the prostate. After prostatectomy medical management of reflux was successful in controlling urinary infection in 34 patients and an operation was performed in 19. Each patient was followed for at least 1 year. PMID- 2578579 TI - Human glioblastoma cells persistently infected with simian virus 40 carry nondefective episomal viral DNA and acquire the transformed phenotype and numerous chromosomal abnormalities. AB - A stable, persistent infection of A172 human glioblastoma cells with simian virus 40 (SV40) was readily established after infection at an input of 450 PFU per cell. Only 11% of the cells were initially susceptible to SV40, as shown by indirect immunofluorescent staining for the SV40 T antigen at 48 h. However, all cells produced T antigen by week 11. In contrast, viral capsid proteins were made in only about 1% of the cells in the established carrier system. Weekly viral yields ranged between 10(4) and 10(6) PFU/ml. Most of the capsid protein producing cells contained enormous aberrant (lobulated or multiple) nuclei. Persistent viral DNA appeared in an episomal or "free" state exclusively in Southern blots and was indistinguishable from standard SV40 DNA by restriction analysis. Viral autointerference activity was not detected, and yield reduction assays did not indicate defective interfering particle activity, further implying that variant viruses were not a factor in this carrier system. Interferon was also not a factor in the system, as shown by direct challenge with vesicular stomatitis virus. Persistent infection resulted in cellular growth changes (enhanced saturation density and plating efficiency) characteristic of SV40 transformation. Persistent infection also led to an increased frequency of cytogenetic effects. These included sister chromatid exchanges, a variety of chromosomal abnormalities (ring chromosomes, acentric fragments, breaks, and gaps), and an increase in the chromosome number. Nevertheless, the persistently infected cells continued to display a bipolar glial cell-like morphology with extensive process extension and intercellular contacts. PMID- 2578581 TI - The regionalization of perinatal services. Summary of the evaluation of a national demonstration program. AB - The success of modern perinatal management techniques has led to the recommendation of the regional organization of perinatal services. This report summarizes the evaluation of a national demonstration program of such regionalization that was funded by the Robert Wood Johnson Foundation (RWJF) in 1975. In both funded regions and comparison areas, the neonatal mortality rates decreased sharply over the decade of the 1970s. This decline was linked to shifts in the hospital of delivery that indicated antepartum risk identification and transfer of management of high-risk pregnancies to tertiary centers for delivery, a change in service pattern consistent with some aspects of regionalization. The centralization of high-risk deliveries appeared so widespread that the special effect of the RWJF program could not be detected. Surveys of surviving 1-year-old infants showed that the decrease in neonatal mortality was accompanied by a decrease in selected morbidity. PMID- 2578582 TI - Cytologic manifestations of cervical and vaginal infections. II. Confirmation of Chlamydia trachomatis infection by direct immunofluorescence using monoclonal antibodies. AB - We found inflammatory patterns of transparent lymphocytes on increased numbers of histiocytes suggestive of chlamydial infection in 68 (56%) of 121 cervical cytologic smears. Chlamydia trachomatis was isolated from 36 (53%) of those with and only two (4%) of those without such inflammatory patterns. Direct stain with fluorescein-conjugated monoclonal antibodies demonstrated elementary bodies of C trachomatis in 30 (79%) of the 38 culture-positive patients, including 29 of the culture-positive patients who had an inflammatory cytologic pattern suggestive of C trachomatis infection. Thus, Papanicolaou smears can be screened for inflammatory pattern, and separate endocervical smears from patients with a pattern suggestive of chlamydial infection can then be stained by immunofluorescence to confirm the presence of C trachomatis infection. This two step approach detected 29 of 38 infections confirmed by culture in the present study, giving a sensitivity of 76%, a specificity of 100%, and a positive predictive value of 100% in a population having a 31% prevalence of C trachomatis infection. PMID- 2578584 TI - Suppression of experimental hepatic fibrosis by administration of vitamin A. AB - The effect of vitamin A on experimental hepatic fibrosis in rats induced by administration of carbon tetrachloride (CCl4) and pig serum was studied. Vitamin A content in the CCl4-induced cirrhotic liver decreased significantly. Administration of pig serum caused hepatic fibrosis without hepatocytic damage. Vitamin A suppressed induction of experimental hepatic fibrosis by CCl4 and pig serum. Neither hepatocytic injury nor increased activities of serum aspartate aminotransferase and glutamic pyruvic transaminase induced by CCl4 was diminished by vitamin A. These data provide evidence that vitamin A inhibits hepatic fibrogenesis and that this effect may be mediated by an action on stellate cells rather than hepatocytes. PMID- 2578583 TI - Identification of three types of granules in neutrophils of ruminants. Ultrastructure of circulating and maturing cells. AB - The production of three populations of granules during maturation and their occurrence in the neutrophils of a number of ruminants is described. Bone marrow samples from cows, sheep, and goats were fixed, reacted for peroxidase, and examined by transmission electron microscopy. Granule formation was found to occur at three subsequent stages. As in other species including man, it begins with the production of peroxidase-positive granules and is concluded with the production of moderately dark-staining, peroxidase-negative granules of similar size. These two organelles have the characteristics of the azurophil or primary and specific or secondary granules of other species. At an intermediate stage, a different type of peroxidase-negative granule, the large granule, is formed. Its profile is round and markedly larger than those of azurophil and specific granules. The large granules initially have a loose, undulated membrane and fill gradually with matrix which in early forms consists of a central core. Fully developed large granules have a sharply defined membrane and a pale, very uniform content. The two types of peroxidase-negative granules can be distinguished by their sizes and times of formation and also by the appearance of their content which is more coarse and darker in the specific granules. Mature neutrophils from cows, goats, sheep, and an ibex were also examined. Two features are common to all cells viewed: the presence of three types of granules and the preponderance of the large granule population. The results of this study, together with evidence from cell fractionation experiments, suggest that the large granules are a characteristic property of the neutrophils of ruminants. PMID- 2578585 TI - Peribronchiolar fibrosis in lungs of cats chronically exposed to diesel exhaust. AB - This study reports the quantitative changes in the pulmonary proximal acinar region following chronic exposure to diesel exhaust and following an additional 6 months in clean air. Cats (13 months of age) from a minimum disease colony were exposed to clean air (eight cats for 27 months and nine cats for 33 months), diesel exhaust for 8 hours/day, 7 days/week (nine cats for 27 months), or diesel exhaust for 27 months followed by 6 months in clean air (10 cats). Morphologic and morphometric evaluation using light microscopy and scanning and transmission electron microscopy revealed two major exposure-related lesions in proximal acinar regions of lungs of cats: peribronchiolar fibrosis associated with significant increases in lymphocytes, fibroblasts, and interstitial macrophages containing diesel particulate-like inclusions and bronchiolar epithelial metaplasia associated with the presence of ciliated and basal cells and alveolar macrophages containing diesel particulate-like inclusions. Peribronchiolar fibrosis was greater at the end of the 6 months in clean air following exposure, whereas the bronchiolar epithelial metaplasia was most severe at the end of exposure. Following an additional 6 months in clean air the epithelium more closely resembled the control epithelial cell population. The labeling index of terminal bronchiolar epithelium was significantly increased at the end of exposure but was not significantly different from controls or exposed cats following an additional 6 months in clean air. The ultrastructural appearance of epithelial cells remained relatively unchanged following diesel exhaust exposure with the exception of diesel particulate-like inclusions. Total lung collagen, expressed as hydroxyproline per left caudal lobe, was apparently increased (although the difference was not significant) in lungs of cats allowed to recover 6 months in clean air. Newly synthesized collagen (evaluated as the amount of cross-link-derived aldehydes in collagen) was significantly increased to more than twice the control values. The ratio of collagen aldehydes to hydroxyproline was also significantly increased. These observations imply that chronic exposure to diesel exhaust has a persistent fibrogenic effect on the proximal acinar region of the lung. PMID- 2578586 TI - Histochemical examination of glycoconjugates of epithelial cells in the human fallopian tube. AB - In human fallopian tubes, secretory cells made up about 70% and ciliated cells most of the remainder of the epithelium. At the light microscopic level, lectin peroxidase conjugates and other methods demonstrated on secretory cells a surface glycocalyx containing glycoconjugates with fucose residues, terminal sialic acid beta-galactose disaccharides, and sulfate esters. Secretory cells also expressed ABO blood group antigens, on their surface, staining for terminal alpha-N acetylgalactosamine and alpha-galactose in blood group A and B subjects, respectively. The glycocalyx coating the cilia of all ciliated cells contained an acidic glycoconjugate with terminal sialic acid-beta-galactose disaccharides. Ciliated cells ranged from strongly positive to negative in staining for blood group ABO antigens, fucose, and terminal beta-galactose. The glycocalyx on the surface of cilia differed from that on the secretory cell surface in lacking sulfate esters and possessing terminal sialic acid-beta-galactose disaccharides cytochemically unlike those on secretory cells. Cytoplasmic granules, presumably secretory in nature, stained for blood group antigen in secretory cells of some specimens. Two lectin conjugates with affinity for the core region of N glycosidically linked oligosaccharides revealed bodies interpreted as lysosomes in ciliated and secretory cells of most specimens. The latter lectins also stained mast cells intensely, presumably because of affinity for N acetylglucosamine. The luminal surface of endothelial cells stained heavily for fucose and for a terminal sialic acid-beta-galactose disaccharide like that on the surface of cilia. The staining for carbohydrate did not vary qualitatively, and the ratio of secretory to ciliated cells did not differ with the phase of the menstrual cycle. The salpingeal epithelium in two patients with inactive endometrium did not differ from the others. The epithelium in a specimen from a patient with uterine fibroids showed foci of mucous metaplasia, containing a nonsulfated sialylated glycoconjugate. At the electron microscopic level, fucosylated glycoconjugate was visualized with a specific lectin conjugate on the surface of the secretory cells but not on the surface of ciliated and endothelial cells. Infrequent cytoplasmic granules containing mucosubstance apparently provided the cell mechanism in secretory cells for collecting and transporting material from biosynthetic sites to the glycocalyx.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2578587 TI - Production of monoclonal antibodies directed against antigenic determinants common to the alpha- and beta-chain of bovine brain S-100 protein. AB - BALB/c mice were immunized with S-100 protein, which was isolated from bovine brain. The first fusion resulted in the cloning of three stable hybridoma lines (S1-61-64, S1-61-65, S1-87-4) that produced monoclonal antibodies against S-100 protein. The hybridoma lines obtained from a second fusion (S2-20, S2-95) were not stable and antibody production ceased early during cloning. Immunoblotting results showed that all antibodies reacted with antigenic determinants shared by both the alpha- and beta-subunit of S-100 protein. These antigenic sites appeared to differ from the calcium-binding site since immunoblotting against other calcium-binding proteins sharing this site (calmodulin, carp parvalbumin, oncomodulin) was negative. Despite the fact that the immunoblotting reactions of the antibodies obtained from both fusions were indistinguishable, different immunohistologic labeling patterns could be observed. These antibodies have proven to be excellent reagents for the immunocytochemical detection of S-100 in normal and pathologic human tissue. PMID- 2578588 TI - The continuing problem of carcinoma of the pancreas. AB - The courses of 208 patients with adenocarcinoma of the pancreas were reviewed. The lesion was located in the head of the pancreas in 142 patient, (68%) and of these, in 22 patients the diagnosis was confirmed histologically at postmortem examination; 21 patients underwent laparotomy and biopsy with a 33% operative mortality and a 3.4-month average survival; 89 patients underwent biliary and/or gastric bypass with a 24% mortality and 4.8-month average survival; 10 patients underwent pancreaticoduodenectomy with a 20% mortality and 14.6-month average survival. The lesion was located in the body or tail of the pancreas in 77 patients (32%); and, of these, 15 patients had histologic confirmation of clinical diagnoses at postmortem examination; 19 patients underwent biopsy of extra-abdominal metastases and survived an average of 1.4 months; 27 patients underwent laparotomy and biopsy with a 26% operative mortality and 3.5-month average survival; 4 patients underwent gastric and/or biliary bypass with a 50% mortality and 4.5-month average survival; one patient underwent noncurative distal pancreatectomy and survived 1 month postoperatively. No patient was cured of his disease. Of the 55 operative survivors of biliary bypass alone for carcinoma of the head of the pancreas, 5 (9%) required subsequent gastroenterostomy for duodenal obstruction. PMID- 2578589 TI - Dermatofibrosarcoma non-protuberans: description and report of five cases of a morpheaform variant of dermatofibrosarcoma. AB - Five cases of dermatofibrosarcoma are reported. All showed features typical of dermatofibrosarcoma protuberans except that in four cases, and a portion of the fifth case, no protusion of the tumor was noted clinically despite the rather advanced stage of growth of the tumor. These lesions resembled morphea or a morpheaform basal cell carcinoma clinically but could be recognized as "dermatofibrosarcoma non-protuberans" by physicians who had observed a previous case. PMID- 2578590 TI - An apparent danazol-induced primary hepatocellular carcinoma: case report. AB - This paper presents an apparent case of danazol-induced primary hepatocellular carcinoma in a 49-year-old patient, following two years of continuous therapy with this inhibitor of pituitary gonadotrophin. Discontinuation of the drug failed to cause regression of the tumour. PMID- 2578591 TI - Amelioration of the deleterious effects of platelets activated during cardiopulmonary bypass. Comparison of a thromboxane synthetase inhibitor and a prostacyclin analogue. AB - Thrombocytopenia and platelet dysfunction are commonly seen after cardiopulmonary bypass. In addition, the microvascular bed of ischemic myocardium is a potent stimulus for platelet deposition and microvascular plugging. Thus, it would appear theoretically advantageous to provide pharmacologic protection of platelets by inhibiting their response to activating agents and thereby preventing their loss into the extracorporeal circuit; this would further inhibit myocardial platelet deposition and the deleterious effects therein. Twenty-one mongrel dogs were placed on cardiopulmonary bypass with 30 minutes of normothermic global ischemia. They were randomly assigned to receive pretreatment with an infusion of saline (control, n = 8), a thromboxane synthetase inhibitor (RO-22-4679, n = 5), or a prostacyclin analogue that does not produce hypotension (ZK 36,374, n = 8). The platelet count in those animals treated with ZK 36,374 was significantly higher at the end of the experiment than in the control group (102.8 +/- 10.7 X 10(3) versus 69.7 +/- 10.6 X 10(3), p less than 0.01); the animals treated with RO-22-4679 had a platelet count between the other two groups (92.8 +/- 14.8 X 10(30)), which was not significantly different from either. Myocardial platelet deposition was measured with indium 111-labeled platelets. Those animals treated with ZK 36,374 had a much lower level of platelet deposition than the group of controls; again the RO-22-4679 group had values between the other two. Finally, myocardial blood flow after global ischemia and cardiopulmonary bypass, measured with radioactive microspheres, was significantly higher in the ZK 36,374 group than in the control group. We conclude that ZK 36,374 prevents platelet consumption during cardiopulmonary bypass over and above that seen with inhibition of thromboxane synthesis alone. It also prevents deposition of platelets into the myocardium after global ischemia and we presume by that mechanism increases myocardial blood flow. PMID- 2578592 TI - Inosine pranobex and mucocutaneous herpes. PMID- 2578593 TI - Low maternal serum alpha-fetoprotein and Down syndrome. PMID- 2578594 TI - Matrix proteins of influenza A and B viruses possess common antigenic determinants. PMID- 2578595 TI - Amniotic fluid AFP levels and Down syndrome. PMID- 2578596 TI - [Synchronization therapy as a palliative measure in incurable head and neck tumors]. AB - Despite all progress in the therapy of malignant head and neck tumours, about 50% of our patients succumb to their carcinoma or its metastases. For these patients, palliative measures which, at least temporarily, will improve their general condition and the function of respiration as well as food intake, are missing. One, and at the presents perhaps the best, palliative therapy seems to be the so called synchronization therapy. This therapeutic concept will be discussed here in consideration of experimental basic research and the clinical results. Radiation treatment after partial synchronization of the tumour cells leads with acceptable side effects in more than a half of all cases to a satisfactory or good general condition and food intake, and in nearly one-third of the patients to a distinct prolongation of their life under tolerable circumstances. Additionally, the abatement of tumorous pain and the possibility of ingestion give rise to a clear improvement of the psychic situation of the patient. PMID- 2578597 TI - Analgesic effects of antihistaminics. AB - The literature provides considerable evidence indicating that several, but not all antihistaminics, are indeed analgesic agents and some are analgesic adjuvants as well. Those for which effectiveness is reported includes diphenhydramine, hydroxyzine, orphenadrine, pyrilamine, phenyltoloxamine, promethazine, methdilazine, and tripelennamine. The proposed mechanisms of analgesic action of antihistaminics are reviewed and discussed. The literature suggests that more than one mechanism of action exists for them. There is considerable evidence suggesting that histaminergic and serotoninergic central pathways are involved in nociception and that antihistaminic drugs can modulate their responses (1). The evidence for a role for norepinephrine and dopamine and the effects of antihistaminics on them are less well established. Still other pathways have been proposed. A greater understanding of pain mechanisms will aid in elucidating the role of antihistaminics in analgesia. PMID- 2578598 TI - Alpha-fetoprotein favours accumulation of estrone but not arachidonic acid into the fetal and new-born rat brain. AB - Tritriated estrone or arachidonic acid, two high affinity ligands for rat alpha fetoprotein (AFP), were injected into adult, pregnant or newborn Sprague Dawley rats in order to evaluate their possible transfer into the brain. This study shows that the developing brain accumulates the estrogen but not the fatty acid, suggesting that the uptake of AFP by the developing brain is a mechanism for transporting estrogens, but not fatty acids. PMID- 2578599 TI - Effect of proteases on the beta-thromboglobulin radioimmunoassay. AB - Rat peritoneal mast cells and mast cell granules were evaluated by radioimmunoassay for the presence of beta-thromboglobulin and platelet factor 4. The initial assays indicated that a beta-thromboglobulin cross reacting material was released from mast cells by compound 48/80 in a similar dose-dependent manner as histamine release. The material was also found to be associated with purified granules. However, the use of protease inhibitors in the buffers completely abolished the positive assays. Further evaluation of the effects of various proteases on the beta-thromboglobulin assay indicated that elastase would also generate a false positive assay which could then be neutralized by the use of alpha 1-antitrypsin as a protease inhibitor. There was no protease effect on the platelet factor 4 radioimmunoassay which always showed no detectable amounts with mast cells, granules or proteases. These results clearly indicate the artifactual positive assays which can arise when using certain radioimmunoassay tests in the presence of cell proteases. The use of protease inhibitors is a necessary control when applying a radioimmunoassay to a system with potentially active proteases. PMID- 2578600 TI - Various proteinase inhibitors decrease prolactin and growth hormone release by anterior pituitary cells. AB - Proteinase inhibitors were tested for their ability to inhibit prolactin (PRL) and growth hormone (GH) release by cultured anterior pituitary cells of the rat. Inhibitors of microbial origin (chymostatin, elastatinal, leupeptin) had either no or a moderate effect on hormone release while some tripeptide aldehydes, especially those with lysine at their C terminus, inhibited markedly PRL and to a lesser extent GH release. Boc-DPhe-Phe-lysinal was the most effective on lactotrophs inhibiting PRL release more than 50% at 10(-4) M. The site(s) of action of tripeptide aldehydes remain to be elucidated. PMID- 2578601 TI - Curriculum evaluation: status and options. AB - A questionnaire was used to ascertain: the status of the curriculum; curriculum characteristics; factors which have been useful in facilitating and improving the curriculum; opinions of the teaching staff on various ways of improving the educational process; and frequency of utilization of various teaching methods and audio-visual aids. The questionnaire was sent to 100 randomly selected faculty members (about 60% of total faculty members). The responses were statistically analysed to explain and elucidate the nature of the curriculum, factors or agents which have influenced the curriculum, the pattern of utilization of teaching methods and audio-visual aids, and the problems which have inhibited the rate of change. The implications of these findings for facilitating and improving the educational process are discussed. PMID- 2578602 TI - Ascending myelopathy after chemotherapy for central nervous system acute lymphoblastic leukemia: correlation with cerebrospinal fluid myelin basic protein. AB - Ascending myelopathy developed in a previously irradiated 10-year-old boy after intraventricular methotrexate and cytosine arabinoside were given for central nervous system relapse of acute lymphoblastic leukemia. The course was fatal in 10 weeks. Cerebrospinal fluid myelin basic protein levels, indicating a demyelinative process, rose prior to the onset of clinical symptoms and remained at very high levels until death. Myelin basic protein may be useful as a predictor of chemotherapy-associated neurotoxicity. PMID- 2578603 TI - Desensitization of beta-adrenergic receptor-mediated vascular smooth muscle relaxation. AB - Responsiveness to catecholamines may be blunted after prolonged exposure to an agonist; this phenomenon, termed desensitization, is often mediated by receptor down-regulation. beta-Adrenergic receptors mediate relaxation of vascular smooth muscle. We have examined the possibility that this response may be desensitized after prolonged exposure to increased concentrations of epinephrine. Rats were treated with epinephrine infusions (300 micrograms/kg/hr from a minipump) for 7 days and had levels of plasma epinephrine 70-fold greater than those of controls. The mesenteric artery rings from the epinephrine-treated rats contracted normally when exposed to serotonin; however, the extent of relaxation promoted by the beta adrenergic agonist isoproterenol was blunted (86 +/- 4 vs. 43 +/- 9%; p less than 0.05). Acetylcholine and nitroglycerine, which may act through a cyclic GMP mechanism, caused virtually identical relaxation responses in both control and epinephrine-treated groups. To determine the mechanism for the loss in responsiveness to isoproterenol, we measured adrenergic receptors in individual mesenteric arteries using [125I]cyanopindolol. Specific binding of [125I]cyanopindolol was found to have the expected characteristics of interaction with beta receptors. There was no difference in the number of beta-adrenergic receptors between control and epinephrine-treated animals (24 +/- 5 vs. 26 +/- 6 fmol/mg of protein), although there was significantly marked down-regulation of beta-adrenergic receptors in hearts (23 +/- 2 vs. 10 +/- 1 fmol/mg of protein; p less than 0.001) and lungs (172 +/- 29 vs. 76 +/- 7 fmol/mg of protein; p less than 0.01) in the same rats. The ability of isoproterenol to stimulate cyclic AMP production in the mesenteric arteries from the two groups was not significantly different (20.3 +/- 3.5 vs. 23.8 +/- 4.7 pmol of cAMP/mg of protein/2 min). Furthermore, mesenteric artery relaxation was found to be decreased in response to the cyclic AMP analogue dibutyryl cyclic AMP (45 +/- 2.0 vs. 28 +/- 2.0%; p less than 0.001) in the epinephrine-infused rats. These data suggest that the desensitization of beta-adrenergic receptor-mediated smooth muscle relaxation may be caused by a mechanism distal to cyclic AMP production. PMID- 2578604 TI - Triphenylmethylphosphonium blocks the nicotinic acetylcholine receptor noncompetitively. AB - Triphenylmethylphosphonium (TPMP) blocked the nerve-elicited twitch tension of frog sartorius muscles by 50% at a concentration of about 20 microM. This neuromuscular blockade by TPMP, which originated at the level of the nicotinic receptor, was due in part to the ability of the drug to block the quiescent receptor by degrees that depended on the TPMP concentration and on membrane potential. In addition, the blockade was markedly enhanced when the receptor was activated by acetylcholine. Finally, TPMP shortened the lifetimes of ACh activated ion channels. These findings were interpreted as follows. Under resting conditions, TPMP shifted the equilibrium of the receptor channel complex toward the desensitized state. TPMP united with the activated ion channel to shorten channel lifetime and to deepen the blockade. High concentrations (greater than or equal to 50 microM) of TPMP altered muscle action potentials and often increased, by about 30-fold, the frequency of miniature endplate potentials. PMID- 2578605 TI - Assay and time course of 5-fluorouracil incorporation into RNA of L1210/0 ascites cells in vivo. AB - A method for determination of levels of incorporation of nonradiolabeled 5 fluorouracil (FUra) into RNA (F-RNA) in tissue samples is shown to be applicable to tissues in vivo. BDF1 mice bearing L1210 ascites cells were injected intraperitoneally with [14C]FUra, 100 mg/kg. The time course of F-RNA levels in L1210 cells was determined by following the radiolabeled drug, and by NaB3H4 labeling of isolated and derivatized nucleoside. RNA ribonucleotides were obtained by KOH hydrolysis of perchloric acid precipitates of cell sonicates. FUMP nucleotides were separated from remaining nucleotides by DEAE-cellulose chromatography. FUMP fractions were treated with alkaline phosphatase, and FUrd was separated from non-FUrd nucleoside contaminants by additional DEAE-cellulose chromatography. FUrd was quantitated by periodate oxidation of ribose and NaB3H4 reduction of the resulting nucleoside dialdehydes. Isolation of tritiated FUrd trialcohol from remaining tissue contaminants and background radioactivity was done by silica gel thin layer chromatography. Comparison of results obtained by isolation of [14C]FUrd with results of NaB3H4 labeling of the same samples showed parallel results with comparable biological standard deviations, although the tritium method consistently gave slightly lower values. The peak level of F-RNA at 3 hr was 1 base substitution per 174 normal nucleotides. The level of F-RNA after 3 hr declined slowly, so that at 96 hr there still remained 1 FUra base per 597 normal nucleotides. Serial determinations of RNA content showed marked decreases, on the basis of either DNA or protein level, that continued up to 96 hr after FUra administration. These biochemical effects are among the most prolonged reported for FUra, suggesting the possibility that F-RNA represents a storage compartment for release of toxic metabolites and emphasize the need for additional study of RNA effects at long time points. Our method for assay of F RNA appears to be suitable for study of biopsy specimens of tumors and normal tissues following nonradiolabeled-FUra administration. PMID- 2578606 TI - Cytotoxicity and the inhibition of ribosomal RNA processing in human colon carcinoma cells. AB - The effects of six nucleoside and base analogs, 5-fluorouracil, 5-azacytidine, sangivamycin, toyocamycin, 8-azaguanine, and tubercidin, on ribosomal RNA processing and cell viability were examined in the colon carcinoma cell line HT 29. Exposure of HT-29 cells to various concentrations of each of these compounds for 24 hr produced two distinct types of results. Toyocamycin, 5-fluorouracil, and tubercidin caused an exponential type of cell lethality resulting in 3-4 log reduction of cell viability, while sangivamycin, 8-azaguanine, and 5-azacytidine produced a gradual and self-limiting type of cell lethality resulting in no greater than a 1 log reduction of cell viability. Likewise, the effects of these drugs on rRNA processing resulted in their classification into two groups: toyocamycin, 5-fluorouracil, and tubercidin caused an abnormal accumulation of the 45 S precursor to rRNA, while sangivamycin, 8-azaguanine, and 5-azacytidine did not cause an accumulation of 45 S RNA. Sangivamycin, 8-azaguanine, and 5 azacytidine all produced an inhibitory effect on protein synthesis, while tubercidin inhibited protein synthesis at a concentration similar to that which caused the accumulation of 45 S RNA, and toyocamycin and 5-fluorouracil had no effect on protein synthesis at concentrations at which 45 S RNA accumulated. These results show that cells are much less capable of resuming normal proliferative activity after exposure to nucleoside or base analogs which cause the accumulation of 45 S rRNA precursor, than to those which act by other mechanisms. PMID- 2578607 TI - Photodecomposition of 1-nitropyrene and other direct-acting mutagens extracted from diesel-exhaust particulates. AB - The effect of irradiation with wavelengths of 320-418 nm on direct-acting mutagenicity of 1-nitropyrene (1-NP) and particulate-matter extracts of a direct injecting diesel engine was examined. The activity of samples in the Ames test with and without addition of S9 mix in Salmonella typhimurium strain TA98, TA100 and TA1538 decreased with increasing irradiation energy. Visible light was sufficient to destroy the mutagenicity of a 0.1-mM 1-NP solution. The same was true for particulate matter crude extracts as well as the transitional and oxygenate subfractions isolated by column chromatography. UV spectroscopy, thin layer chromatography and GC-MS analysis were performed to characterize the irradiation products of 1-NP. The mechanism of photodecomposition of 1-NP at different wavelengths and the significance of this finding for the evaluation of health risks from diesel vehicles are discussed. PMID- 2578608 TI - The assessment of the mutagenic potential of vehicle engine exhaust in the Ames Salmonella assay using a direct exposure method. AB - A method for the assessment of the mutagenic activity of vehicle engine exhaust in the Ames assay is described in which the bacterial strains used (TA98 and TA98/DNP) are exposed to the freshly produced engine exhaust using a "Cassella' slit sampler. The method is found to be effective both in the presence and absence of metabolic activation, using Aroclor-1254-induced rat liver S9 fractions. A comparison is made between the direct exposure method and the standard methods involving the collection of particulate samples on glass fibre filters and the testing of various extracts of these samples. Possible uses of the direct exposure testing method are suggested and the effect of sampling techniques on the results obtained in the Ames assay is also discussed. PMID- 2578609 TI - Delay in the fetal globin switch in infants of diabetic mothers. AB - In the normal fetus, a switch from production of hemoglobin F (alpha 2 gamma 2) to hemoglobin A (alpha 2 beta 2) occurs at 28 to 34 weeks of gestation. In the fetus with beta-hemoglobinopathy or beta-thalassemia, this switch proceeds despite the morbidity that results when production of beta-globin is abnormal or reduced. Since insulin has recently been shown to induce renewed expression of some inactive genes, we studied globin biosynthesis during the natural evolution of the fetal globin switch under conditions of hyperinsulinemia, which occurs in infants of diabetic mothers. Such infants develop in a hyperglycemic environment, which produces reactive hyperinsulinemia. The normal increase in beta-globin production from pre-switch levels did not occur in 9 of 10 such infants at term, as compared with 11 normal infants, in whom the switch occurred by 36 to 39 weeks of gestation (P less than 0.0001). The delay in the switch from gamma-globin to beta-globin in this unique clinical setting may allow identification of physiologic factors that can modulate developmental gene suppression. PMID- 2578610 TI - Controlled clinical trial of peritoneal lavage for the treatment of severe acute pancreatitis. AB - We performed a multicenter, randomized, controlled clinical trial of therapeutic peritoneal lavage (2 liters per hour for three days) in 91 patients with severe acute pancreatitis. Patients were entered into the study if severe pancreatitis was indicated by multiple laboratory criteria or diagnostic peritoneal lavage. All patients received full supportive treatment. The median time between the onset of symptoms and randomization was 38 hours. Forty-six patients were assigned to the control group and 45 to the lavage group. There were 13 deaths (28 per cent) and 16 patients with major complications (35 per cent) in the control group, as compared with 12 deaths (27 per cent) and 17 patients with major complications (38 per cent) in the lavage group. Lavage did not appear to modify the length of survival, the incidence of pancreatic collections (pseudocysts or abscesses), or the plasma amylase concentration. Considering the statistical power of the design, we conclude that the outcome of severe pancreatitis was not greatly, if at all, influenced by the regimen of peritoneal lavage used in this study. PMID- 2578611 TI - Common epithelial cancer of the ovary (2). PMID- 2578612 TI - Virus vaccines. PMID- 2578613 TI - Regulation of a protein synthesis initiation factor by adenovirus virus associated RNA. AB - A small RNA accumulating late in adenovirus infection is required for efficient protein synthesis, although not specifically for the translation of viral proteins. This RNA maintains the activity of an initiation factor catalysing the earliest step of polypeptide chain initiation. PMID- 2578614 TI - Haemoglobin switching in human embryos: asynchrony of zeta----alpha and epsilon-- -gamma-globin switches in primitive and definite erythropoietic lineage. AB - Haemoglobin switching in humans provides a unique model for investigating the mechanisms underlying expression of a developmentally regulated gene family. Numerous studies have focused on the switch from fetal to adult (that is, gamma-- -beta) globin, but little is known about the embryonic----fetal (that is, zeta--- alpha and epsilon----gamma) switches, as well as the transition from 'primitive' yolk sac to 'definitive' liver erythropoiesis. Here we have studied the embryonic ---fetal haemoglobin switches in yolk sac, liver and circulating blood erythroblasts from 25 embryos and 6 fetuses. Globin synthesis was also evaluated in purified 'primitive' and 'definitive' erythroblasts. Primitive erythroblasts synthesize essentially zeta and epsilon chains at 5 weeks and alpha- and epsilon globin with a minor aliquot of zeta and gamma chains at 6-7 weeks, whereas definitive erythroblasts produce alpha and epsilon + gamma + beta-globin at 6 weeks but only alpha and gamma + beta chains from 8 weeks onward. In both lineages the zeta----alpha and the epsilon----gamma switches are asynchronous, the former preceding the latter. Furthermore, zeta- and beta-globin synthesis is restricted to primitive and definitive erythroblasts respectively. These findings are discussed in terms of a monoclonal model for haemoglobin switching in early human ontogeny. PMID- 2578615 TI - Complete nucleotide sequence of the AIDS virus, HTLV-III. AB - The complete nucleotide sequence of two human T-cell leukaemia type III (HTLV III) proviral DNAs each have four long open reading frames, the first two corresponding to the gag and pol genes. The fourth open reading frame encodes two functional polypeptides, a large precursor of the major envelope glycoprotein and a smaller protein derived from the 3'-terminus long open reading frame analogous to the long open reading frame (lor) product of HTLV-I and -II. PMID- 2578616 TI - Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment. AB - Vertebrate rod photoreceptors hyperpolarize when illuminated, due to the closing of cation-selective channels in the plasma membrane. The mechanism controlling the opening and closing of these channels is still unclear, however. Both 3',5' cyclic GMP and Ca2+ ions have been proposed as intracellular messengers for coupling the light activation of the photopigment rhodopsin to channel activity and thus modulating light-sensitive conductance. We have now studied the effects of possible conductance modulators on excised 'inside-out' patches from the plasma membrane of the rod outer segment (ROS), and have found that cyclic GMP acting from the inner side of the membrane markedly increases the cationic conductance of such patches (EC50 30 microM cyclic GMP) in a reversible manner, while Ca2+ is ineffective. The cyclic GMP-induced conductance increase occurs in the absence of nucleoside triphosphates and, hence, is not mediated by protein phosphorylation, but seems rather to result from a direct action of cyclic GMP on the membrane. The effect of cyclic GMP is highly specific; cyclic AMP and 2',3' cyclic GMP are completely ineffective when applied in millimolar concentrations. We were unable to recognize discrete current steps that might represent single channel openings and closings modulated by cyclic GMP. Analysis of membrane current noise shows the elementary event to be 3 fA with 110 mM Na+ on both sides of the membrane at a membrane potential of -30 mV. If the initial event is assumed to be the closure of a single cyclic GMP-sensitive channel, this value corresponds to a single-channel conductance of 100 fS. It seems probable that the cyclic GMP-sensitive conductance is responsible for the generation of the rod photoresponse in vivo. PMID- 2578617 TI - Enhancement of calcium current in Aplysia neurones by phorbol ester and protein kinase C. AB - One of the molecular mechanisms capable of regulating the physiological properties of neurones is the phosphorylation of ion channels and other cellular components by cyclic AMP-dependent protein kinase. Another protein kinase present in high concentrations in the mammalian brain is protein kinase C (a calcium/phosphatidylserine/diacylglycerol-dependent protein kinase), but there is no direct evidence, as yet, for the involvement of this enzyme in the control of neuronal excitability. We now present evidence that activation of endogenous protein kinase C by the tumour-promoting phorbol ester TPA (12-O-tetradecanoyl- phorbol-13-acetate), or intracellular injection of the purified enzyme, enhances the voltage-sensitive calcium current in bag cell neurones of the mollusc Aplysia. PMID- 2578619 TI - G to A substitution in the distal CCAAT box of the A gamma-globin gene in Greek hereditary persistence of fetal haemoglobin. AB - The sequence 5'TTGGPyCAAT 3' (the 'CCAAT box') is a constituent of the promoter region of many eukaryotic and prokaryotic genes and is believed to play a part in promoter function. A characteristic of the two fetal human globin genes (A gamma and G gamma) is a duplication of a 12-base pair (bp) sequence containing the CCAAT box. Here we report a G----A substitution in the TTG sequence of the distal CCAAT box of the A gamma-globin gene in an individual with the A gamma (Greek) type of hereditary persistence of fetal haemoglobin (HPFH). This represents the first report of a natural mutation of the CCAAT box in a eukaryotic gene. The fact that this transition is associated with inappropriate expression of the A gamma gene in adult life suggests that the CCAAT box (or its surrounding sequences) may have a role in the developmental control of gamma-globin genes. PMID- 2578618 TI - Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle. AB - The recent development of techniques for recording currents through single ionic channels has led to the identification of a K+-specific channel that is activated by cytoplasmic Ca2+. The channel has complex properties, being activated by depolarizing voltages and having a voltage-sensitivity that is modulated by cytoplasmic Ca2+ levels. The conduction behaviour of the channel is also unusual, its high ionic selectivity being displayed simultaneously with a very high unitary conductance. Very little is known about the biochemistry of this channel, largely due to the lack of a suitable ligand for use as a biochemical probe for the channel. We describe here a protein inhibitor of single Ca2+-activated K+ channels of mammalian skeletal muscle. This inhibitor, a minor component of the venom of the Israeli scorpion, Leiurus quinquestriatus, reversibly blocks the large Ca2+-activated K+ channel in a simple biomolecular reaction. We have partially purified the active component, a basic protein of relative molecular mass (Mr) approximately 7,000. PMID- 2578621 TI - Too much hype. PMID- 2578620 TI - A point mutation in the A gamma-globin gene promoter in Greek hereditary persistence of fetal haemoglobin. AB - Hereditary persistance of fetal haemoglobin (HPFH) is a benign condition characterized by the production in adulthood of more than 1% fetal haemoglobin (HbF, alpha 2 gamma 2) in the absence of erythropoietic stress. Several genetic types have been discerned based on the level of HbF produced, the relative contributions of the duplicated fetal (G gamma and A gamma) globin genes, and the presence or absence of deletions involving the beta and delta genes in cis to the mutation. Greek HPFH is a non-deletion variety in which heterozygotes produce 10 20% HbF, predominantly due to overproduction of the A gamma chain. We have cloned a 40-kilobase (kb) region of the beta-globin cluster from a Greek HPFH allele and report here that a point mutation (G----A) occurs 117 base pairs (bp) 5' to the cap site of the A gamma-globin gene, just upstream of the distal CCAAT sequence. The corresponding region of the G gamma-globin gene is normal. We discuss the implications of this finding for the developmental regulation of globin gene expression. PMID- 2578622 TI - Unique allelic restriction fragments of the human Ha-ras locus in leukocyte and tumour DNAs of cancer patients. AB - White blood cell DNA from cancer patients and DNA from tumours and tumour-derived cell lines frequently demonstrated allelic restriction fragments of the Harvey ras oncogene locus not found in the unaffected population. The presence of such unusual alleles may be linked to susceptibility to cancer. PMID- 2578623 TI - Cyclic AMP-dependent protein kinase closes the serotonin-sensitive K+ channels of Aplysia sensory neurones in cell-free membrane patches. AB - Selected actions of neurotransmitters and hormones on ion channels in nerve and muscle cells are now thought to be mediated by cyclic AMP-dependent protein phosphorylation. Although the cyclic AMP-dependent protein kinase (cAMP-PK) affects the cellular properties of several neurones, its mode of action at the single-channel level has not been characterized. In addition, little is known about the identity or subcellular localization of the phosphoproteins that control channel activity and, in particular, whether the critical substrate proteins are cytoplasmic or membrane-associated. In Aplysia sensory neurones, serotonin produces a slow modulatory synaptic potential mediated by cAMP-PK that contributes to presynaptic facilitation and behavioural sensitization. Previously, we have found that serotonin acts on cell-attached membrane patches to produce prolonged all-or-none closures of a specific class of K+ channels (S channels) whose gating is weakly dependent on voltage and independent of intracellular calcium. We demonstrate here that in cell-free membrane patches from Aplysia sensory neurones, the purified catalytic subunit of cAMP-PK produces all-or-none closures of the S channel, simulating most (but not all) aspects of the action of serotonin on cell-attached patches. This result suggests that protein kinase acts on the internal surface of the membrane to phosphorylate either the channel itself or a membrane-associated protein that regulates channel activity. PMID- 2578625 TI - Activation of chromaffin cell Ca2+ channels by novel dihydropyridine. PMID- 2578624 TI - Unique structure of murine interleukin-2 as deduced from cloned cDNAs. AB - Interleukin-2 (IL-2) is a lymphokine originally described as a humoral factor required for the continued proliferation of activated T-cell clones. It also seems to be involved in the mitogenic response of thymocytes, in augmenting natural killer cell activity, in the generation of cytotoxic T cells and in the induction of other lymphokines such as gamma-interferon and a B-cell growth factor (BCGF-1). More recently, there has been evidence for the involvement of IL 2 per se in the stimulation of B-cell growth (ref. 10 and T. Kishimoto and J. Vilcek, personal communications). We have reported previously the cloning and expression of a human IL-2 complementary DNA. The cDNA encodes biologically active IL-2 which would consist of 153 amino acids, including a signal sequence. Because so much of the work on IL-2 has been done in the human and mouse, we sought to obtain cDNA encoding murine IL-2, and we now report the cloning, expression and sequence analysis of murine IL-2 cDNAs. The longest cDNA insert encodes a polypeptide of 169 amino acids, containing unique repeats of a CAG sequence which would encode 12 consecutive glutamine residues within the active IL-2 molecule. PMID- 2578626 TI - Interferons and oncogenes. PMID- 2578627 TI - Characterization of the branch site in lariat RNAs produced by splicing of mRNA precursors. AB - The branch site of lariat RNAs produced during the splicing of the first two late leader exons of adenovirus-2 has a structure of (formula; see text) There is a distinct complementarity between sequences preceding the adenosine at the branch site and the 5' terminus of the intervening sequence. PMID- 2578628 TI - Light-induced reduction of cytoplasmic free calcium in retinal rod outer segment. AB - The response of retinal rod photoreceptors to light consists of a membrane hyperpolarization resulting from the decrease of a light-sensitive conductance in the outer segment. According to the calcium hypothesis, this conductance is blocked by a rise in intracellular free Ca triggered by light, a notion supported by the findings that an induced rise in internal Ca leads to blockage of the light-sensitive conductance and that light triggers a net Ca efflux from the outer segment via a Na-Ca exchanger, suggesting a rise in internal free Ca in the light. We have now measured both Ca influx and efflux through the outer segment plasma membrane and find that, contrary to the calcium hypothesis, light seems to decrease rather than increase the free Ca concentration in the rod outer segment. This result implies that Ca does not mediate visual excitation but it probably has a role in light adaptation. PMID- 2578629 TI - Effects on the photoresponse of calcium buffers and cyclic GMP incorporated into the cytoplasm of retinal rods. AB - It is generally accepted that the light response in retinal rods involves a reduction of ionic permeability (predominantly to Na+) in the plasma membrane of the outer segment and that this is mediated by an internal messenger which diffuses between the disk and plasma membranes. There is controversy, however, over the identity of the diffusible substance; two alternative schemes have received widespread support (for review see refs 1,2). According to the 'calcium hypothesis', light stimulates the release into the cytoplasm of calcium, leading to the blockage of channels which are normally open in darkness, whereas based on the 'cyclic nucleotide hypothesis', cyclic GMP causes the opening of channels in the dark, but is hydrolysed by a light-activated phosphodiesterase. We report here effects of introducing calcium buffers and cyclic GMP into the rod cytoplasm by means of a patch pipette, which seem to be inconsistent with the calcium hypothesis. PMID- 2578630 TI - Na channels in skeletal muscle concentrated near the neuromuscular junction. AB - Neuronal function depends crucially on the spatial segregation of specific membrane proteins, particularly the segregation associated with sites of synaptic contact. Understanding the factors governing this localization of proteins is a major goal of cellular neurobiology. A conspicuous example of synaptic specialization is the almost exclusive localization of vertebrate skeletal muscle acetylcholine (ACh) receptors to the subsynaptic membrane of the neuromuscular junction (for example, refs 1,2). The localization of other membrane proteins in skeletal muscle has been much less studied, but a knowledge of their distribution is crucial for understanding the factors governing regional specialization. We have explored the distribution in muscle of the voltage-gated Na channel responsible for the action potential using the loose patch-clamp technique, and have measured Na currents in 5-10 micron-diameter membrane patches as a function of distance from the end plate region of snake and rat muscle fibres. Here we report that the Na current density immediately adjacent to the endplate is 5-10 fold higher than at regions away from the endplate. The increased Na current density falls off rapidly with distance, reaching the background level 100-200 micron from the endplate. Although one might expect ACh receptors to be concentrated near the region of ACh release, such a concentration for Na channels, which propagate the impulse throughout the length of the cell, is surprising and suggests that factors similar to those responsible for concentrating ACh receptors at the endplate also operate to concentrate Na channels. PMID- 2578631 TI - Expression of a minichromosomal variant surface glycoprotein gene in Trypanosoma brucei. AB - African trypanosomes contain numerous variant surface glycoprotein (VSG) genes, but express only one at a time. When different VSG genes are activated by gene duplicative or non-duplicative mechanisms, antigenic variation occurs. Although transcriptionally inactive VSG genes can have either an intra-chromosomal or a telomeric location, all expressed VSG genes so far examined are telomeric. Some VSG genes are located on minichromosomes of approximately 100 kilobases (kb), but all those thus far described are transcriptionally inactive. We have found that the single copy of the IsTat 1.1 VSG gene in the IsTaR 1 serodeme has a telomeric location on a minichromosome when inactive. When it is activated, it is not duplicated and remains on a minichromosome. These data indicate that minichromosomes contain or can acquire all the DNA sequences necessary in cis for VSG gene expression and antigenic switching. Of several sequences associated with expressed VSG genes or their transcripts, only the 76-base pair (bp) repeat element was found in minichromosomal DNA. Variant antigenic types (VATs) which occurred immediately before and after VAT-1, expressed VSG genes located on larger chromosomes. Thus, different chromosomes can act as VSG gene expression sites. PMID- 2578632 TI - Detection of a cell proliferation-inhibiting factor in the cell-free ascitic fluid of intraperitoneal mouse tumors. AB - Three cell-free ascitic fluids: MCG3AF, P815AF and SL2AF were obtained from mice injected with MCG3, P815 and SL2 tumor cells, respectively. These ascitic fluids were tested in culture with different normal and tumor mouse cells showing an inhibitory effect on 3H-thymidine and 3H-uridine uptake. The MCG3AF, selected for further study, was tested with a larger number of mouse tumor cell lines and also with normal mouse and human cells. This ascitic fluid inhibited 3H-thymidine and 3H-uridine uptake in all cases. The cell proliferation-inhibiting factor(s) (CPIF) detected in MCG3AF was found to be thermostable and nondialyzable. Further biochemical analysis showed that CPIF is a lipid but with no relationship with very low-density lipoproteins. PMID- 2578633 TI - Indocyanine green angiography of choroidal neovascular membranes. AB - The choroidal circulation was studied in 27 eyes with choroidal neovascular diseases by means of fluorescein and indocyanine green (ICG) angiography. In 10 of the cases the disciform response was seen to be associated with either watershed zones of the choroidal circulation or with areas of choroidal circulatory disturbance. This is consistent with the theory that hypoxic regions of the choroid are the underlying cause of macular disciform response. PMID- 2578634 TI - Effect of intrauterine ethanol exposure on fetal lung growth. AB - Lung weight, DNA, RNA, protein, and total body weight were analyzed in fetuses from 14 pregnant Sprague-Dawley rats fed a nutritionally complete liquid diet containing v/v 6% ethanol (ethanol group). Each ethanol rat was matched with an isocalorically pair-fed animal (control group) who received the same liquid diet with carbohydrate substituted for ethanol. The rats were killed on day 20 of gestation. The mean maternal blood ethanol concentration at 0700 h on day 20 was 170 +/- 22 (SE) mg/dl. Compared to controls, ethanol fetuses had reduced body weight (21%), lung dry weight (39%), lung wet weight/body weight ratio (10%), DNA (21%), RNA (25%), protein (28%), and protein/DNA ratio (8%) (p less than 0.05). The results indicate that prenatal ethanol exposure inhibits cellular growth in the fetal lung, resulting in hypoplastic lungs which have fewer and smaller cells. The effect on the lung appears to be greater than on the body as a whole. These hypoplastic lungs may be predisposed to the development of pulmonary disease and may explain observations of more frequent and severe lower respiratory infections in children with prenatal ethanol exposure. PMID- 2578636 TI - Industrial control of medical research. PMID- 2578635 TI - Effects of orally administered caffeine on cellular response in protein energy malnourished neonatal rat brain. AB - The purpose of this study was to determine the effects of caffeine on growing rats and how protein energy malnutrition can modify these potential effects. Caffeine (1,3,7-trimethylxanthine) is not only the most commonly consumed, neurally active stimulant in our daily lives, but it is widely used in the management of apnea in the premature neonate. One group of dams (20%) (n = 6) was begun on a 20% protein diet ad libitum. The second group (6%) (n = 4) was begun on a 6% protein diet. A third group (20% + C) (n = 4) was pair-fed to group 1 (20%) with the 20% protein diet, but beginning on day 3 the pups received 10 mg/kg body weight of caffeine via intragastric feeding needle every other day. The fourth group (6% + C) (n = 5) was pair-fed with group 2 (6%) with the 6% protein diet and the pups received 10 mg/kg of caffeine in the same manner as the 20% + C group from day 3. Although the 6% protein diet was associated with the expected reduced body and brain growth, there were no additional growth alterations associated with caffeine administration in either the 20% or 6% diet groups. This growth failure was accompanied by the expected reductions in total whole brain DNA, RNA, protein, and cholesterol content regardless of whether caffeine was received or not. Effects of caffeine which were similar in both diet groups included an increase in brain RNA content and concentration and an increase in the RNA/DNA ratio. However, there were differential effects of caffeine seen depending on diet group assignment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578637 TI - Automatic scanning extrastimulus pacemaker to treat ventricular tachycardia. AB - Many investigators have reported the use of various permanent pacemaking modes in the long-term management of patients with recurrent ventricular tachycardia. The three general types of antitachycardic pacemakers are: (1) underdrive; (2) burst; and (3) scanning pacemakers. Such devices have been activated externally or have had automatic activation. Each antitachycardic pacemaking modality has known technical and physiologic limitations. A serious limitation of dual-demand underdrive pacemakers is that they are usually successful only for tachycardias with a rate below 160 bpm because a random stimulus is needed for conversion. Therefore, this modality is seldom useful in patients with symptomatic sustained ventricular tachycardia in which rates are generally greater than 160 bpm and/or hemodynamic compromise occurs rapidly. Although others have reported the successful use of burst pacemakers in the control of ventricular tachycardia, this technique may cause acceleration of ventricular tachycardia and induction of ventricular fibrillation. Programmable automatic scanning pacemakers have been used successfully to treat paroxysmal supraventricular tachycardia and have been used recently in combination with antiarrhythmic agents to control ventricular tachycardia. This report outlines the use of an automatic scanning pacemaker alone for the treatment of symptomatic ventricular tachycardia in a patient who was unable to tolerate conventional antiarrhythmic medications. PMID- 2578638 TI - Subcostal M-mode echocardiography of the right atrial wall in evaluation of cardiac arrhythmias and pacing. AB - Subcostal M-mode echocardiography of the right atrial wall in combination with the simultaneously recorded nondiagnostic electrocardiogram is useful in the recognition of various rhythm disturbances. Each arrhythmia has a characteristic right atrial wall motion pattern. Flat and hidden P-waves can be accurately detected throughout the cardiac cycle and supraventricular tachycardias with aberration can be distinguished from ventricular tachycardia with AV dissociation. This echocardiographic technique is of special value in the follow up of physiological pacemakers because atrial capture and sensing malfunctions can be reliably detected. Finally, it can also facilitate the programming of atrial channels output + sensitivity, and recognition of the pacemaker syndrome. PMID- 2578639 TI - Implantable defibrillator electrode systems: a brief review. AB - Since the first report of a defibrillation attempt with an intracardiac catheter electrode nearly 30 years ago, investigators have developed implantable electrode systems consisting of metal disks, endocardial catheters, and epicardial patches. These early efforts demonstrated the feasibility of low-energy reversion of ventricular tachyarrhythmias, and also provided some insight into the mechanisms of fibrillation and defibrillation. This review describes the evolution of implantable defibrillator electrode systems. Early investigators attempted defibrillation with submuscularly implanted metal disks or a disk electrode paired with an endocardial catheter electrode. Electrode design emphasis turned to transvenous catheter systems with electrodes placed in the right ventricle and right atrium. A more successful configuration placed the proximal electrode in the superior vena cava. In an effort to ensure proper placement of the distal electrode in humans, the catheter was replaced with an epicardial patch. More recently, a combination of electrodes and multiple pulses has substantially reduced the energy required to defibrillate. Effective electrode systems that can convert lethal arrhythmias with a minimum of energy will aid in making implantable cardioverters and defibrillators the therapy of choice in patients at high risk of sudden coronary death. PMID- 2578640 TI - Role of invasive electrophysiologic studies in the evaluation and treatment of supraventricular tachycardia. AB - Electrophysiologic studies have provided new insights into the mechanisms responsible for supraventricular arrhythmias and have enabled investigators to evaluate with precision the acute effects of pharmacologic, physiologic, electrical, and surgical interventions. Not all patients with supraventricular arrhythmias require invasive studies, however, since empiric drug trials will often be adequate for management. At present, the clinical indications for study include the following: (1) for diagnosis of tachycardia mechanism when scalar ECG analysis is uncertain; (2) for assessment of risk of future life-threatening arrhythmia; and (3) as a rapid means of assessing future therapy when sporadic arrhythmias are likely to be poorly tolerated. Innovations that include surgical and catheter ablations of tachycardia pathways and antitachycardia pacing devices hold great promise and in the future, will provide nonpharmacologic options for patients poorly controlled by or intolerant of drug therapy. PMID- 2578642 TI - A solution to difficult power frequency interference on ECG recordings. AB - Line, or 50 Hz, interference is a common feature of ECG recordings where either the instrument performance is unsatisfactory or the tissue electrode preparation is inadequate. With the superior performance of modern ECG machines, the electrode preparation required is minimal. Any interference present on the recording can usually be eliminated by a reapplication of the electrodes. Where it is persistent, this may be due to a magnetic field interacting with the loop formed by the electrode leads and the subject. Reducing the loop area by repositioning the electrode leads will usually produce a clear recording. A particular area in an ECG department, designated for routine ECG recordings, produced tracings contaminated with over 0.4 mV peak to peak of interference despite all efforts to eliminate it. After investigation, a novel solution was developed which actively reduces the environmental power line magnetic field. Three adjacent examination couches have been treated and are now satisfactory for routine ECG determinations with no noticeable interference. PMID- 2578641 TI - Ventriculoatrial conduction: a cause of atrial malpacing in AV universal pacemakers. A report of two cases. AB - Retrograde atrial activation during ventricular pacing has often been a cause of intermittent or persistent arrhythmias (pacemaker-mediated tachycardia) in AV universal pacemakers. We recently encountered two cases in which VA conduction was responsible for atrial malpacing in patients with an implanted AV universal pacemaker, one programmed in DDD and one in DVI mode. Atrial malpacing was induced by the atrial refractoriness due to retrograde activation. In the first patient, it was observed when the pacemaker was programmed to a rate of 110 ppm (lower rate) and an AV interval of 200 ms in order to check crosstalk. In the second patient, it was observed after ventricular premature contractions. PMID- 2578643 TI - Myopotential inhibition of unipolar pacing in children. AB - Myopotential inhibition of unipolar demand pacing systems has been shown to be a frequent occurrence in adults with transvenous pacing systems in which the pulse generators are implanted adjacent to the pectoralis muscle. To evaluate this problem in children, most of whom have epimyocardial systems and abdominal wall generator implants, 50 patients underwent electrocardiographically monitored exercise and 24-hour ambulatory electrocardiograph monitoring. Patients' ages at the time of study ranged from less than one year to 18 years, and weights ranged from less than 5 kg to 63 kg. Sixteen different models of pulse generators from five manufacturers were involved. Pacing modes were VVI, DVI, AAI, VDD, and DDD. Forty-seven patients had epimyocardial systems. None of the patients was symptomatic as a result of myopotential inhibition. Only three patients (6%) had any evidence of myopotential inhibition and all three demonstrated this inhibition on both monitored exercise and ambulatory electrocardiograph. The inhibition was eliminated by reprogramming the sensitivity levels of the three generators without compromising R-wave sensing. Thirteen of the remaining 35 patients with multiprogrammable generators had induction of myopotential inhibition when exercised after temporary programming to maximal sensitivity settings. Myopotential inhibition of unipolar demand pacing appears to be less frequent and less problematic in the pediatric population, even though they are physically quite active. It is not clear whether this is a function of patient size or the abdominal wall position of the pulse generator.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578644 TI - Effect of enflurane, isoflurane, and halothane on pacing stimulation thresholds in man. AB - Volatile anesthetic agents are often used in patients who require temporary epicardial pacing after cardiopulmonary bypass (CPB). However, the effect of anesthetic agents on energy stimulation thresholds is unknown. After CPB, 24 patients under diazepam-narcotic-pancuronium anesthesia ventilated with an FIO2 = 1.0 received equipotent concentrations of either enflurane, isoflurane, or halothane. Using temporary epicardial electrodes, energy stimulation thresholds were calculated using the data derived from a pacing systems analyzer. Volatile anesthetics do not change energy stimulation thresholds from those already present under diazepam-narcotic-pancuronium anesthesia. PMID- 2578645 TI - Long-term management of recurrent paroxysmal tachycardia by cardiac burst pacing. AB - Sixteen patients with either recurrent symptomatic supraventricular tachycardia (SVT) (ten) or ventricular tachycardia (VT) (six) unresponsive to drug treatment underwent insertion of chronic overdrive cardiac pacing devices for arrhythmia control. All patients with SVT followed for longer than 2.5 years required concomitant drug therapy for rhythm control. In addition, one of the ten patients required amiodarone and three required nonpharmacologic therapy (catheter ablation of the atrioventricular junction (one), surgical ablation of the Kent bundle and/or bundle of His (two). In the six patients with VT, only one patient used the device successfully. In the other five patients, either the arrhythmia failed to respond to burst overdrive pacing (three) or overdrive acceleration resulted (two). One death in the latter group was related to induction of rapid VT followed by ventricular fibrillation. Long-term follow-up of patients with paroxysmal SVT shows that virtually all require concomitant drug therapy and may require aggressive medical or surgical procedures for arrhythmia control. Use of ventricular overdrive pacing for those with VT appeared singularly disappointing in that pacing proved either ineffective (three) or resulted in overdrive acceleration (two) in 5/6 patients. PMID- 2578646 TI - Temporary AVI pacing by chest wall stimulation. AB - Temporary atrial pacing (coded AVI pacing) has recently been proposed to assess atrial capture in patients with unipolar dual chamber pacemakers. This pacing mode can usually be achieved by programming the ventricular output to a subthreshold value. In patients with noncommitted bifocal pacemakers, AVI pacing can also be obtained by prolonging the programmed AV delay allowing for spontaneous conduction after atrial capture. However, in patients with prolonged AV conduction and a low aventricular stimulation threshold, ventricular stimulation cannot be prevented using the forementioned procedures. Using chest wall stimulation, we developed and tested a new method of temporary AVI pacing in patients with noncommitted DDD or DVI pacemakers. PMID- 2578647 TI - Acute and long-term atrial and ventricular stimulation thresholds with a steroid eluting electrode. AB - Thirty leads with a steroid-eluting electrode (Medtronic 4003 and 4503) have been implanted in 24 patients, 11 in the atrium and 19 in the ventricle. Six patients received the steroid lead in both atrium and ventricle. The stimulation thresholds were followed using Elema pulse generators with Vario function in 15 patients (11 atrial leads and 10 ventricular leads) during 11 +/- 3 months (mean +/- SD). At 0.5 ms pulse duration the mean atrial and ventricular thresholds were 0.55 Volt +/- 0.22 and 0.39 Volt +/- 0.22 respectively at implant, 0.94 Volt +/- 0.13 and 0.82 Volt +/- 0.16 after 12 months. During the entire follow-up period both atrial and ventricular mean thresholds never exceeded 1 V. PMID- 2578648 TI - Reversion mode activation by myopotential sensing in a ventricular inhibited demand pacemaker. AB - Pacemaker follow-up in a 72-year-old woman revealed occasional failure to sense and pace, which was confirmed by Holter monitor. Neither reprogramming the pacemaker sensitivity nor repositioning the lead resolved the problem. A recheck of the Holter recordings revealed pacing and sensing failures were concurrent with "baseline artifact," suggestive of myopotentials. Furthermore, the inappropriate pacing spikes occurred at a rate of 90 pulses per minute (ppm). It was theorized that myopotential sensing was alternately inhibiting the pacer and activating the reversion mode, an asynchronous rate of 90 ppm. Reprogramming the unit to a lower sensitivity restored normal pacer function. PMID- 2578649 TI - Activity-sensing, rate-responsive pacing: improvement in myocardial performance with exercise. AB - A sensor that detects body activity by low frequency sonic impulses has been incorporated in a pacemaker so that body activity may be translated to an increased pacing rate in response to exercise. The pacemaker is designed for patients who may benefit from an increased cardiac output mediated by an increased heart rate during exercise. Following permanent pacemaker implantation, six patients (mean age 69 years) entered a single blind, randomized, crossover trial for comparison of activity-sensing, rate-responsive pacing (A) to fixed rate demand pacing (D). Ventricular function was assessed by gated radionuclide ventriculography at rest and at exercise, while exercise capacity was assessed by treadmill performance, along with measurements of oxygen consumption and carbon dioxide production. Total treadmill duration and maximum oxygen consumption were similar in the two pacing modes (A = 284 +/- 244 s, 13.4 +/- 3.4 ml O2/min/kg; D = 256 +/- 250 s, 11.7 +/- 3.7 ml O2/min/kg). Anaerobic threshold, however, was significantly improved (A = 266 +/- 199 s, (p less than .05), 13.0 +/- 2.2 ml O2/min/kg (p less than .01); D = 231 +/- 208 s, 10.8 +/- 2.3 ml O2/min/kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578650 TI - Interpretation of dual chamber pacemaker electrocardiograms. AB - A diagramming system has been developed to assist in interpreting dual chamber pacemaker electrocardiograms. The system is based on the ladder diagram principle but uses two separate ladders, one for the ECG allowing proper representation of atrial A-V and ventricular activation, and a second ladder diagram below it for pacemaker events. The system is applicable to all current single and dual chamber pacing modes and is easy to draw. The ladder diagram allows the logical sequence of timing events to be easily illustrated, and pacemaker malfunction becomes clearly recognizable as a conflict between the ECG events ladder and the pacemaker timing ladder. The system is easy to apply and may eventually prove suitable for automatic generation by computer utilizing sophisticated pacemaker telemetry. PMID- 2578651 TI - Multiple accessory pathways: a combined electrophysiological and radionuclide study. AB - Electrophysiological study in a patient with Wolff-Parkinson-White syndrome revealed multiple accessory pathways: Kent bundle and Mahaim nodoventricular and fasciculoventricular fibers. Radionuclide phase imaging disclosed two distinct ventricular activation sequences during sinus rhythm or slow atrial pacing and during fast atrial pacing. The third activation pattern could be recorded after injection of ajmaline, which abolished signs of preexcitation in the electrocardiogram. Phase image in combination with pacing and pharmacological interventions can, at least in some cases, detect complex preexcitation syndromes noninvasively. PMID- 2578652 TI - Measurement of pacing threshold. AB - Thresholds in constant current and constant voltage are reported for 405 CPI 4118 (Cardiac Pacemakers, Inc.) tined leads. In 98% of the cases, the constant current threshold was equal to or lower than 0.6 mA. A constant voltage threshold was equal to or lower than 0.5 V in 96% of the cases. Three external pacemakers and two pacing system analyzers were evaluated as threshold testing devices. For analyzing the waveforms of current and voltage stimuli, a calibrated isolation amplifier was used. We could not find a definite difference between the value, at which pacing is lost with reduction of the pulse generator output, and the value at which increase reestablishes pacing. PMID- 2578653 TI - Physiological versus single-rate ventricular pacing: a double-blind cross-over study. AB - Previous comparisons of physiological and single-rate ventricular pacing are mostly based on open studies. The present investigation was designed to control possible biases of such a study design with the aim to investigate effects of the two pacing modes on maximal and submaximal exercise tolerance and the subjective feeling of well-being of the patients. Forty-four patients treated with atrioventricular synchronous pacemakers for more than 12 months participated in the study. Their pacemakers were randomly programmed to one 3-week long period of ventricular inhibited and a similar period of atrioventricular synchronous ventricular inhibited pacing. Thereafter, they went through echocardiography, symptom-limited maximal exercise test and answered a questionnaire on subjective symptoms. The study was blind since neither the patients nor the physician conducting the exercise tests were informed of pacing mode. The mean maximal exercise tolerance increased 14% (p less than 0.01) on atrioventricular synchronous pacing. Arterial lactate, respiratory rates and perceived exertion ratings during submaximal levels of exercise were higher on ventricular inhibited pacing, as well as symptoms scored during the two 3-week periods. A majority of patients improved their functional class during atrioventricular synchronous pacing and preferred the physiological pacing mode. PMID- 2578654 TI - Control of refractory supraventricular arrhythmias after unsuccessful closed chest His bundle ablation. AB - Six patients underwent attempted catheter ablation of the His bundle for control of refractory supraventricular tachyarrhythmias. Permanent complete heart block was achieved in only three patients. All six patients have remained asymptomatic without antiarrhythmic medications over a follow-up period of six to 17 months (mean 10 months). There were no complications of the procedure apart from mild elevation of creatine kinase levels in three patients. In this series, resumption of atrioventricular (AV) conduction following attempted His bundle ablation was not associated with recurrence of symptomatic arrhythmias. Preservation of AV conduction may also obviate the need for permanent ventricular pacing. PMID- 2578655 TI - Use of atrial pacing in a young population. AB - Forty pediatric and young adult patients (1-20 years; mean, 11 years of age) had implantation of atrial demand (AAI) pacemakers over a 5.5 year period. Nineteen were implanted by epicardial technique and 21 transvenously. Standard lithium single chamber pulse generators and standard atrial leads were used. Operative stimulation thresholds were better for transvenous leads than for epicardial (0.75 volts vs. 1.5 volts at 0.5 ms) (p less than 0.05). Pulse width thresholds at a mean of 1.5 years were not significantly different (0.11 ms for transvenous vs. 0.18 for epicardial). No patient developed AV block. Eight patients (four epicardial and four endocardial) required reoperation during the mean 3.5 year follow-up--four because of lead problems and four because of persistent tachycardia. Of the six patients who received an automatic antitachycardia pacemaker, only one had persistent symptoms while seven of eight who received a standard unit continued to have symptoms. Twenty-eight of 29 symptomatic patients without tachycardia became asymptomatic. Atrial pacing appears to be a safe and effective therapy for children with sick sinus syndrome. PMID- 2578656 TI - Cumulative seven-year index, Volumes 1-7, 1978-1984. PMID- 2578658 TI - Diabetic ketoacidosis. How to treat and, when possible, prevent. AB - Treatment and prevention of diabetic ketoacidosis (DKA) should be guided by an understanding of the metabolic decompensation that occurs in this medical emergency. The primary cause of DKA is insulin deficiency, which may be precipitated by infection or other forms of stress. As hyperglycemia exceeds the renal threshold, it leads to osmotic diuresis, electrolyte loss, and eventually dehydration. Treatment, therefore, consists primarily of insulin administration and replacement of fluid and electrolytes. Likewise, prevention hinges on avoiding insulin deficiency by tight control of blood glucose levels and compensation for stress. Because of the metabolic derangements of DKA, some laboratory tests can be misleading and need to be carefully interpreted. PMID- 2578657 TI - Identification of prostate and other cancers by two-dimensional protein electrophoresis. AB - Some cancers are so undifferentiated as to preclude their identification, and this hinders selection of an appropriate therapy. The systematic analysis and cataloguing of electrophoresed proteins from identified cancers and their comparison with the protein patterns from histologically indeterminate cancers should provide a general means of identifying the latter. PMID- 2578659 TI - The hospice concept. Comfort care for dying patients. AB - The hospice movement is a relatively new but fast-growing approach to caring for the terminally ill. Central to the hospice concept is a team of care-givers who provide care at all levels, not only to the patient but to the family as well. Although the physician serves as adviser, the patient or family makes the final decisions regarding care. The patient is permitted to maintain control as long as possible, thus preserving the right to die with dignity. Home care is a goal of the hospice concept, but in some situations hospital or nursing home care is required. Hospice care does not end with the death of the patient but extends to helping the family during the bereavement period. PMID- 2578660 TI - [Prevention trial of thrombosis with pentosane polysulfate in intracardiac dynamic explorations]. PMID- 2578661 TI - Small peptides induce antibodies with a sequence and structural requirement for binding antigen comparable to antibodies raised against the native protein. AB - Antisera were raised against the chemically synthesized peptide corresponding to each epitope of three foot-and-mouth disease virus strains. Peptide synthesis was further used to determine which amino acid residues in each epitope are important for the specificity of antisera raised against the whole virus. The specificity of the antibody paratope for its epitope was shown to depend on structure as well as sequence. Anti-virus sera demonstrated a greater specificity for the homologous peptide than did the anti-peptide sera. Two of the three peptides were able to induce neutralizing antibodies against the homologous virus. The specificities of the antibodies present in the anti-peptide sera were also inferred from the reactions of each with related sets of peptides. The cross reactions observed for the anti-peptide sera were readily explained in terms of the antibody specificities determined to be present. The findings also suggest that the diversity of antibodies raised against small peptides is limited and is determined by the immune system. A similar limited response to the native protein was observed, which may account for the high frequency with which anti-peptide sera react with the native homologous protein. PMID- 2578662 TI - Functional reconstitution of the purified brain sodium channel in planar lipid bilayers. AB - The ion conduction and voltage dependence of sodium channels purified from rat brain were investigated in planar lipid bilayers in the presence of batrachotoxin. Single channel currents are clearly resolved. Channel opening is voltage dependent and favored by depolarization. The voltage at which the channel is open 50% of the time is -91 +/- 17 mV (SD, n = 22) and the apparent gating charge is approximately 4. Tetrodotoxin reversibly blocks the ionic current through the sodium channels. The Ki for the tetrodotoxin block is 8.3 nM at -50 mV and is voltage dependent with the Ki increasing e-fold for depolarizations of 43 mV. The single channel conductance, gamma, is ohmic. At 0.5 M salt concentrations gamma = 25 pS for Na+, 3.5 pS for K+, and 1.2 pS for Rb+. This study demonstrates that the purified brain sodium channel--which consists of three polypeptide subunits: alpha (Mr approximately 260,000), beta 1 (Mr approximately 39,000), and beta 2 (Mr approximately 37,000)--exhibits the same voltage dependence, neurotoxin sensitivity, and ionic selectivity associated with native sodium channels. PMID- 2578663 TI - Calcitonin gene-related peptide and its binding sites in the human central nervous system and pituitary. AB - Binding sites for synthetic human 125I-labeled calcitonin gene-related peptide (125I-CGRP) have been demonstrated in membranes of the human nervous system. Binding was high in the cerebellar cortex (1.35 +/- 0.27 fmol/mg of tissue; mean +/- SEM), spinal cord (1.06 +/- 0.27 to 1.27 +/- 0.23 fmol/mg), and nucleus dentatus (1.02 +/- 0.15 fmol/mg), intermediate in the inferior colliculus (0.80 +/- 0.14 fmol/mg) and substantia nigra (0.75 +/- 0.14 fmol/mg), low in the neocortex, globus pallidus, nucleus caudatus, hippocampus, amygdala, superior colliculus, thalamus, and hypothalamus (0.15-0.32 fmol/mg), and negligible in spinal and sympathetic ganglia and pituitary (less than 0.04 fmol/mg). Autoradiography showed distinct 125I-CGRP binding over the molecular and Purkinje cell layers of the cerebellar cortex and over the substantia gelatinosa posterior of the spinal cord. The highest levels of CGRP-like components were recognized in the dorsal part of the spinal cord and the pituitary gland. In the ventral part of the spinal cord as well as in the pituitary and thyroid glands, CGRP values were higher when measured by radioreceptorassay as compared to RIA, indicating that at least two CGRP-like components are present. The predominant CGRP-like peak on HPLC had the retention time of synthetic human CGRP. Immunohistochemistry revealed the presence of a dense plexus of CGRP immunoreactive nerve fibers in the dorsal horn of the spinal cord. PMID- 2578664 TI - Common evolutionary origin of alpha 2-macroglobulin and complement components C3 and C4. AB - A comparison of the sequence of the subunit of human alpha 2-macroglobulin (alpha 2M; 1451 amino acid residues) with that of murine complement component pro-C3 (1639 amino acid residues) reveals eight extended regions of sequence similarity. These regions contain between 19% and 31% identically placed residues and account for 75% and 67%, respectively, of the polypeptide chains of alpha 2M and pro-C3. Published sequence data for complement component C4 show that segments of this protein match well with corresponding stretches in alpha 2M and pro-C3. It is proposed that alpha 2M, C3 and C4, which all contain a unique activatable beta cysteinyl-gamma-glutamyl thiol ester, have a common evolutionary origin and are homologous proteins. Several larger regions of low sequence similarity indicate the presence of structural domains in each of these proteins that specifically modify an underlying common gross structure. The quartets of basic residues in pro-C3 and pro-C4, at which cleavage takes place to produce the mature subunits of these proteins, and most of the residues forming the anaphylatoxin peptides of C3 and C4 (C3a and C4a) are absent in alpha 2M. In addition, C3 and C4 contain large portions, which extend beyond the COOH terminus of alpha 2M. PMID- 2578665 TI - Sequential changes in DNA methylation patterns of the rat phosphoenolpyruvate carboxykinase gene during development. AB - The cytosolic phosphenolpyruvate carboxykinase [PEPCK; GTP:oxaloacetate carboxy lyase (transphosphorylating), EC 4.1.1.32] gene was isolated from a rat genomic library, and a map of the methylatable sites C-C-G-G and G-C-G-C has been constructed. The extent of methylation of 18 sites in the PEPCK gene in adult liver, kidney, spleen, and heart muscle and in fetal liver has been analyzed using the 5-methylcytosine sensitive enzymes Hpa II and Hha I. This analysis revealed extensive undermethylation of the PEPCK gene in the adult liver and kidney (PEPCK-expressing tissue), whereas the gene in adult spleen and heart muscle as well as in fetal liver (PEPCK-nonexpressing tissues) was heavily methylated. However, unlike the gene in the adult nonexpressing tissues, a region in the middle of the gene was found to be partially hypomethylated in fetal liver. This hypomethylation correlates with the competence of the fetal liver gene to be expressed. Treatment of fetuses by in utero injection of 5-azacytidine causes a hypomethylation-associated activation of the PEPCK gene. Taken together, the present findings suggest a sequential loss of methyl groups during development. When related to PEPCK gene expression, the sequential loss of methyl groups demonstrates an early stage prior to transcription characterized by hypomethylation of discrete sites and a later developmental hypomethylation of all sites associated with the mature active PEPCK gene around the time of birth. PMID- 2578666 TI - Friend and Moloney murine leukemia viruses specifically recombine with different endogenous retroviral sequences to generate mink cell focus-forming viruses. AB - A group of mink cell focus-forming (MCF) viruses was derived by inoculation of NFS/N mice with Moloney murine leukemia virus (Mo-MuLV 1387) and was compared to a similarly derived group of MCF viruses from mice inoculated with Friend MuLV (Fr-MuLV 57). Antigenic analyses using monoclonal antibodies specific for MCF virus and xenotropic MuLV envelope proteins and genomic structural analyses by RNase T1-resistant oligonucleotide finger-printing indicated that the Moloney and Friend MCF viruses arose by recombination of the respective ecotropic MuLVs with different endogenous retrovirus sequences of NFS mice. PMID- 2578667 TI - Rearrangement and transcription of a T-cell receptor beta-chain gene in different T-cell subsets. AB - The functionally defined sets of T lymphocytes--helper T cells, cytotoxic T cells, and suppressor T cells--were examined for the possible involvement of a recently identified T-cell receptor beta gene locus in receptor formation. Since gene rearrangements are required for functional gene expression, cloned T-cell lines from each of the groups were surveyed for the expression of unique gene rearrangements. In addition, cell lines that showed gene rearrangements were further tested for the expression of the mature 1.2- to 1.3-kilobase mRNA transcribed from a productive gene rearrangement. The results of such experiments show that helper and cytotoxic T cells may use a common beta chain of the receptor, whereas suppressor cells do so rarely, if at all. PMID- 2578668 TI - Murine monoclonal antibodies to the myelin-associated glycoprotein react with large granular lymphocytes of human blood. AB - Monoclonal antibodies prepared to human myelin-associated glycoprotein were shown to react with a population of human peripheral blood mononuclear cells. The population is similar to the large granular lymphocytes or natural killer cells defined by antibody Leu 7 (also called HNK-1). The population also includes cells exhibiting the Leu 2 marker for suppressor/cytotoxic T cells. The results indicate a shared antigenicity between the nervous system and the immune system and may be relevant to the pathogenesis of demyelinating diseases. PMID- 2578670 TI - Demonstration of inter- and intraspecies differences in serotonin binding sites by antibodies from an autistic child. AB - Serotonin (5-HT) binding sites from bovine and rat cerebral cortex membranes share pharmacological properties that allow both to be subclassified by the same criteria. We show here that [3H]5-HT binding sites from human cortex also possess pharmacological properties that follow the same subclassification scheme as for bovine and rat cortex. In addition, we show that solubilized 5-HT1 and 5-HT3 sites from all three species have an s20,w value of 3.4. Despite these similar pharmacological and physical characteristics, we can demonstrate antigenic differences between receptor types and species. Human 5-HT1A sites can be distinguished from human 5-HT1B, 5-HT2, and 5-HT3 sites and from equivalent sites in rat and bovine cortex. The anti-human 5-HT1A antibodies were discovered in the blood of an autistic child and may have clinical or etiologic significance for this disorder. PMID- 2578669 TI - Electroconvulsive shock increases preproenkephalin messenger RNA abundance in rat hypothalamus. AB - Daily administration of electroconvulsive shock (ECS) to rats for 10 days increased the content of [Met5]enkephalin in the hypothalamus and the striatum by 64% and 45%, respectively. The effect of ECS on the relative abundance of mRNA coding for the enkephalin precursor preproenkephalin was investigated. Analysis by cell-free translation of polyadenylylated RNA and immunoprecipitation of preproenkephalin revealed ECS-elicited increases of 79% and 14% in preproenkephalin mRNA activity in the hypothalamus and striatum, respectively. ECS treatment did not affect the general translational activity of total polyadenylylated RNA from these brain regions. A 32P-labeled probe prepared from a rat preproenkephalin cDNA clone hybridized with an apparently single species of polyadenylylated RNA of approximately equal to 1450 nucleotides from both hypothalamus and striatum. Dot-blot hybridization of polyadenylylated RNA with the rat probe indicated that ECS elicits a 76% increase in the preproenkephalin mRNA abundance in the hypothalamus and no significant change in the striatum. These results suggest that ECS treatment leads to enhanced biosynthesis of the enkephalin precursor in hypothalamic neurons. PMID- 2578671 TI - Internal antigen and immune network. AB - The network hypothesis postulates the existence of internal idiotopic structures which mimic nominal antigens. Experimental evidence for idiotope internal antigen is presented and its implication for the Network hypothesis is discussed. The exploitation of the internal idiotope antigens (or preparation of vaccines) is a realistic possibility. PMID- 2578672 TI - Renal effects of aprotinin, a kallikrein inhibitor in rats in saline diuresis. AB - Administration of aprotinin, a kallikrein inhibitor, to anesthetized rats infused with 0.9% saline solution to expand the extracellular fluid volume resulted in blunted natriuresis and diuresis. Urine flow declined from 27.1 +/- 2.6 to 8.0 +/ 0.9 microliter/min/100 g body wt while sodium and potassium excretion were reduced 63 and 45%, respectively (P less than 0.01). Mean blood pressure and glomerular filtration rate were not significantly altered by aprotinin. Acute or chronic pretreatment with DOCA, to enhance kinin synthesis, failed to modify the renal excretory response to aprotinin suggesting that saline loading alone was able to induce kinin generation fully in these rats. The results indicate that aprotinin enhanced the reabsorption of filtrate in rats expanded with isotonic saline and imply an influence of renal kinins on the tubular transport of salt and water. PMID- 2578673 TI - A role for class-II major histocompatibility complex antigens in the regulation of myelopoiesis. PMID- 2578674 TI - Prenatal diagnosis and screening: present and future. PMID- 2578675 TI - Birth defects epidemiology and surveillance. PMID- 2578676 TI - A model of cardiac electrical activity incorporating ionic pumps and concentration changes. PMID- 2578677 TI - Bilateral shoulder-hand syndrome associated with phenobarbital administration. A case report. PMID- 2578678 TI - Advanced prostatic carcinoma: pulmonary manifestations. AB - To clarify the role of standard chest radiography in prostatic adenocarcinoma, the pulmonary manifestations of 198 patients with Stage D disease were evaluated. All patients were treated with chemotherapeutic protocols allowing for adequate clinical and radiographic correlation. Retrospective interpretation of serial chest radiographs revealed that 35% of our patients had visible intrathoracic abnormalities; however, only 24% of the patients had abnormalities attributable to intrathoracic metastases. Twenty-two percent of patients had pleural effusions, 16% reticular opacities, 3.5% reticulonodular opacities, 8% isolated or discrete pulmonary nodules, and 4.5% adenopathy. Etiologies of these opacities included metastatic disease in 93.5% of those with adenopathy and nodular or reticulonodular opacities, but 39% of pleural effusions and 52% of reticular opacities were best attributed to concomitant processes. Four patients had intrathoracic metastases without bone metastases. Standard chest radiography is a valuable screening procedure that should be correlated with clinical data to differentiate metastases from concomitant processes. PMID- 2578679 TI - Intracranial tumors examined by intraarterial DSA: a comparative angiography study. AB - We compared intraarterial digital subtraction angiography (DSA) studies with those of conventional angiography, performed for 24 patients who had intracranial tumors. Intraarterial DSA is more effective in evaluating tumoral blush and venous phase, but neovascularization can be judged better by conventional angiography. In most cases, intraarterial DSA can replace conventional angiography for the diagnostic and preoperative evaluation of intracranial tumors. However, conventional angiography remains the technique of choice for the evaluation of neovascularization or if the patient is not cooperative. PMID- 2578680 TI - Immunoglobulin idiotypes: analysis of viral antigen-antibody systems. PMID- 2578681 TI - Influence of Na/K pump current on action potentials in Purkinje fibers. AB - Moderate changes in the size of the outward (hyperpolarizing) current that is generated directly by the electrogenic Na/K exchange pump in the surface membrane of cardiac Purkinje fibers can cause substantial alterations in the shape of the action potential, in the level of the diastolic potential, or of the resting potential of quiescent cells, or in the rate of firing of spontaneously active preparations. Transient increments in Na/K pump current, of suitable magnitude, can be elicited experimentally in small canine Purkinje fibers by causing a transient increase in their intracellular Na concentration, [Na]i, and, thereby, a transient increase in the rate of electrogenic Na extrusion. Two techniques were used to increase [Na]i: in the first, the rate of Na extrusion from the cells was temporarily reduced by omitting K ions from the bathing fluid for short periods of time, in the second, the rate of Na entry into the cells was temporarily increased by electrically stimulating the preparations rapidly (e.g., greater than or equal to 2 Hz) for brief periods. After the extracellular K concentration was restored, or after electrical stimulation was stopped, respectively, use of a two-microelectrode voltage-clamp technique allowed the resulting increments in pump current to be measured directly, as changes in holding current. Increments in pump current elicited by these two methods in the same preparation decline with the same exponential time-course. In preparations stimulated electrically at a regular, low rate (e.g., less than or equal to 1 Hz) both methods of temporarily stimulating the Na/K pump cause a marked, transient reduction in the duration of the action potential. A closely similar reduction in action-potential duration to that observed during enhanced pump activity can be elicited by injecting, from an external source, a steady hyperpolarizing current of magnitude similar to that of the increment in pump current recorded in the same preparation under voltage clamp. PMID- 2578682 TI - The effects of intracellular Na on contraction and intracellular pH in mammalian cardiac muscle. AB - Intracellular Na and pH were measured with recessed-tip ion-selective microelectrodes in voltage-clamped sheep cardiac Purkinje fibers. Intracellular Na activity (aiNa) was elevated by inhibiting the Na/K pump. This produced an increase of twitch tension that had a steep dependence on the increase of aiNa. These effects of aiNa on twitch tension are probably mediated by an Na-Ca exchange. An increase of aiNa also produced a component of tonic tension that appears to be produced directly by the Na-Ca exchange. The dependence of tonic tension and aiNa on membrane potential suggests that this exchange process may be voltage-sensitive. The increase of aiNa is associated with an intracellular acidification that appears to be secondary to an increase of [Ca2+]i produced by Na-Ca exchange. Therefore, as well as affecting [Ca2+]i, Na-Ca exchange can under some circumstances influence pHi indirectly, and this complicates the interpretation of changes in tension, since protons and Ca ions have opposite effects on contractile force. PMID- 2578683 TI - Molecular approach to the calcium channel. AB - Tritiated 1,4-dihydropyridines (nimodipine, nitrendipine, nifedipine, PN 200-110) and [3H]D-cis-diltiazem as well as [3H]verapamil were employed to directly identify calcium channels in membranes for excitable tissues. The channels, when probed with 1,4-dihydropyridines, exhibit the following properties: 1,4 Dihydropyridine calcium channel blockers bind in a temperature-dependent, reversible manner and with high affinity (dissociation constants 0.2-2 nM at 37 degrees C) to a finite number of sites. For chiral 1,4-dihydropyridines, the binding is stereoselective. Hill slopes of approximately 1.0 are observed. In brain, heart, and solubilized skeletal-muscle membranes, an absolute requirement for certain divalent cations exists in order to bind the ligands with high affinity. Cooperativity (negative and positive) between Me2+ and 1,4 dihydropyridine binding sites is observed. 1,4-Dihydropyridine binding sites are down-regulated in a complex manner by the optically pure enantiomers of D-600 and verapamil. These channel blockers induce, to a different extent, a low-affinity state of the 1,4-dihydropyridine binding site. It is postulated that this allosteric site, at which these blockers act, is closely coupled to the 1,4 dihydropyridine binding site and that a spectrum of compounds exists that differ in their affinity as well as their intrinsic activity to induce the down regulation. The 1,4-dihydropyridine binding sites are up-regulated by D-cis diltiazem and KB-944. The up-regulation is temperature-dependent and induces a high-affinity state for 1,4-dihydropyridine channel blockers, accompanied by distinct alterations of the kinetics as well as the pharmacological profile of the 1,4-dihydropyridine binding sites. Complex interactions exist between the channel blockers that induce up-regulation and those that induce down-regulation of the binding. For a given radiolabeled 1,4-dihydropyridine, a tissue-specific (but not species-specific) equilibrium binding dissociation constant is observed. Thus, all heart (human, rat, guinea pig, frog, bovine) have the same KD (0.25 nM at 37 degrees C) for, [3H]nimodipine. The same is observed for brain (KD = 0.5 nM) and for skeletal muscle (KD = 1-2 nM). Three subtypes of channels can be distinguished on the basis of the KD and the tissue-specific up-regulation by D cis-diltiazem. Subtype-selective drugs exist; e.g., AQA 39 is an inhibitor of [3H]nimodipine binding at skeletal-muscle calcium channels, but not at brain channels. Despite their different pharmacological and kinetic profiles, calcium channels in skeletal muscle and brain have the same molecular size (Mr) when probed by radiation inactivation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2578684 TI - The measurement of cardiac membrane channels following their incorporation into phospholipid bilayers. AB - This chapter describes the basic properties of integral membrane channels from both cardiac sarcoplasmic reticulum and sarcolemma. Channels are studied, under voltage-clamp conditions, following their incorporation into planar phospholipid bilayers by fusion of isolated native membrane vesicles with preformed membranes. The rate of fusion of vesicles may be influenced by a number of factors including divalent cations and negatively charged phospholipids in the preformed bilayer. Mammalian cardiac sarcoplasmic reticulum contains a monovalent cation selective channel with a single-channel conductance of approximately 150 pico-Siemens in the presence of symmetrical solutions of 500 mM K+ at holding potentials ranging from -60 to +60 mV. The probability of the channel being in the open state is high at positive holding potentials and low at negative holding potentials. Mammalian cardiac sarcolemma contains at least three K+-selective channels and one Cl(-)-selective channel. PMID- 2578686 TI - Three different classes of oral antidiabetic drugs do not increase insulin binding and insulin-induced RNA synthesis in human fibroblast cultures. AB - We describe insulin binding and insulin-mediated RNA synthesis on seven human fibroblasts strains in culture initiated from skin biopsies in the presence of three oral antidiabetic agents, Metformin, Gliquidone, and a non-sulfonylurea antidiabetic drug (B X DF 591 ZW), which belong to different chemical classes. At least at a nontoxic pharmacologic concentration of 1 microgram/ml these drugs did not influence the number and affinity of insulin receptors, nor did they increase the insulin-mediated RNA synthesis. We conclude that cultured fibroblasts do not represent the proper target for an evaluation of an extrapancreatic action of oral antidiabetic drugs. PMID- 2578685 TI - Calmodulin in the regulation of calcium fluxes in cardiac sarcolemma. AB - Three systems mediate the fluxes of calcium across heart sarcolemma: the slow calcium channel (influx), the ATP-dependent calcium pump (efflux), and the Na+/Ca2+ exchanger (efflux, but possibly also influx). Calmodulin regulates the pumping ATPase by direct interaction and also by activating a protein kinase. The Na+/Ca2+ exchanger is modulated by calmodulin via a phosphorylation dephosphorylation cycle. Both the kinase and the phosphatase are membrane-bound and calmodulin-sensitive. The kinase has higher Ca2+ affinity than the phosphatase. PMID- 2578687 TI - [When should ventricular extrasystole be treated?]. PMID- 2578688 TI - Amputation: helping a patient face loss of a limb. PMID- 2578690 TI - Human peripheral blood null lymphocytes stimulated by Staphylococcus aureus Cowan I produce atypical acid-labile interferon in vitro. AB - Peripheral blood mononuclear leucocytes (PBLs) stimulated in vitro by heat-killed formaldehyde-fixed Staphylococcus aureus Cowan I (SACoI) produced acid-labile alpha interferon (IFN-alpha) and, to various extents, also IFN-gamma. The IFN producers resided in nylon wool-nonadherent cells, and monocytes suppressed SACoI induced IFN responses. Further separation of nonadherent PBLs in accordance with expression of surface antigenic markers was performed with a 'panning' technique. The SACoI induced production of IFN in cells that carried neither surface immunoglobulins nor OKT3-defined antigens. These cells were also characterized as OKM1- and OKT10-negative. In contrast, cells with natural killer (NK) activity against K562 erythroleukaemia cells were located in both OKM1- and OKT10-positive and -negative cells. At centrifugation on Percoll density gradients, cells with NK activity and IFN response against SACoI were recovered from light gradient fractions that contained mainly large granular lymphocytes (LGL). Furthermore, the IFN producers were enriched by removal of sheep erythrocyte-rosetting T cells from the Percoll fractions. These SACoI-induced IFN-producing PBLs are LGL but lack certain antigens that are frequently found on NK cells. PMID- 2578689 TI - T-cell chronic lymphocytic leukaemia: anomalous cell markers, variable morphology, and marked responsiveness to pentostatin (2'-deoxycoformycin). AB - 4 men with an unusual variant of T-cell chronic lymphocytic leukaemia are reported. The clinical features differed from the virus-associated T-cell disease reported from Japan, the Caribbean, and the southeastern United States. Cytology was pleiomorphic: cells with cerebriform nuclei resembling Sezary cells and lymphocytes with cytoplasmic granules resembling T-suppressor cells occurred in the same patients. Immunofluorescence studies with monoclonal antibodies suggested that the leukaemia cells expressed determinants of both helper- (OKT4+) and suppressor-(OKT8+) related antigens. The cells were TdT-negative. In all patients the disease was very refractory to conventional cytotoxic agents, but there was prompt and extensive response to the adenosine deaminase inhibitor pentostatin (2'-deoxycoformycin). This agent merits further study in the treatment of T-cell chronic lymphocytic leukaemia. PMID- 2578691 TI - High-dose survival in the lymphocytic choriomeningitis virus infection is accompanied by suppressed DTH but unaffected T-cell cytotoxicity. AB - Provided that intracerebral inoculation is applied, an increase in the virus dose from 10(2) to 10(4) LD50 of lymphocytic choriomeningitis virus (LCMV) leads to strikingly reduced mortality. To analyse the background for this autointerference, we measured several virologic and immunologic variables in mice infected with these doses of virus. In the high-dose mice we found generally higher organ virus titres and serum interferon titres than in the low-dose mice. Since we could demonstrate that virus-specific T-cell cytotoxicity in spleen, peripheral blood, and meningeal exudate was similar after intracerebral infection with large and small virus doses, and since the LCMV infection in the brain qualitatively and quantitatively was independent of the size of virus inoculum, the explanation for the survival of the high-dose animals is obviously not lack of possibilities for interaction between cytotoxic T cells and infected sensitive targets in the central nervous system. On the other hand, high doses of virus caused a clear suppression of the LCMV-specific delayed-type hypersensitivity (DTH). In addition, when splenocytes from high-dose animals were transferred either intravenously or locally into the footpad of newly virus-challenged mice, DTH was markedly suppressed as compared with the response after transfer of spleen cells from low-dose mice. We therefore conclude that autointerference in the LCMV infection is due to a selective suppression of Td function. Large amounts of persistent virus late after infection with high doses of virus suggest a central role for Td function also in virus clearance. Finally, our results indicate the existence of two subsets of K,D region-restricted T cells, one mediating cytotoxicity and the other mediating DTH. This possibility is discussed. PMID- 2578692 TI - Hemolysis following platelet transfusions from ABO-incompatible donors. AB - Two hemolytic transfusion reactions related to isoagglutinins present in group O platelet concentrates are reported. The first, a severe reaction in a group A 10 kg patient, resulted from transfusion of 200 ml of plasma containing a hemolytic anti-A, titer 16, and an IgG anti-A, titer of 32,000. In the second case, a group B adult received between 50 and 70 ml of O plasma with a titer (16,000) of anti B. This was followed by hemolysis of approximately 40 percent of the patient's red cell volume. PMID- 2578693 TI - Generation of mouse cytolytic T cells against human concanavalin A blasts. Involvement of non-MHC determinants in the antihuman response. AB - Normal human peripheral blood lymphocytes (PBL) are incapable of eliciting a significant murine cytotoxic T cell (CTL) response either in vivo or in vitro. However, using a primary in vivo and secondary in vitro stimulation with lectin activated PBL, Thy-l-positive cytotoxic cells were produced. The antigens that these T-cells identified were independent of the serum source employed in the culture medium used for lectin activation. The cells always preferentially lysed cells from the immunizing individual but were also able to lyse target cells from unrelated individuals, regardless of HLA identity or disparity with the immunizing individual, suggesting the presence of both a private (possibly class II antigens) and public specificity. Using the lymphoblasts of different family members as immunogen and targets there was slight preference of the CTL for HLA identical targets with no apparent difference between the lysis exhibited against semiidentical and nonidentical subjects. Monoclonal antibodies directed against HLA DR or beta 2-microglobulin failed to inhibit the cytotoxicity observed in these experiments. It is suggested that under these circumstances of xenogeneic education, non-MHC-restricted T cells may become cytotoxic, and this model may serve as a useful probe to investigate some of the less-well-defined aspects of the T cell repertoire. PMID- 2578694 TI - Quantitative evaluation of testicular biopsies from men with unilateral torsion of spermatic cord. AB - Torsion of the spermatic cord is not uncommon among young men. Various abnormalities in the histology of the contralateral testis have been reported due to unilateral torsion of the spermatic cord. We quantitatively estimated the germ cells from three groups of men: normal individual (Group I), men with unilateral torsion of short duration (Group II), and men with unilateral torsion of long duration or some other condition such as varicocele or intermittent torsion to the contralateral testis (Group III). No significant difference in the number of spermatogonia, spermatocytes, and spermatids of Groups I and II patients was observed. This observation indicates that there was no pre-existing morphophysiologic defect in the testis of Group II patients. Severe damage in the contralateral testis was noted in Group III patients. This indicates that if a damaged testis is retained in the body for a long time, the contralateral testis may be affected. Contralateral testis may also be affected by intermittent torsion or varicocele. PMID- 2578695 TI - Androgen receptors in bladder tumors. AB - Cytosol androgen receptor content of transitional cell bladder cancer tissue was found to be substantially higher than its content in normal bladder mucosa and lower than in control benign prostatic hypertrophy tissue. Tumors arising in female patients had a lower androgen receptor content than those arising in male patients. High-grade tumors had a lower androgen receptor content than low-grade tumors. PMID- 2578696 TI - Testicular gonadal stromal (Sertoli cell) tumor. AB - Eighty-one cases of testicular gonadal stromal tumor have been reported in the literature. An additional case is herein reported. The pathologic, immunohistologic, and histogenetic aspects are presented. PMID- 2578697 TI - Interstitial radiation: short-term palliation or curative therapy? AB - The management of clinically localized prostatic cancer by interstitial implantation of 125I seeds has been under exploration at Memorial Sloan-Kettering Cancer Center for thirteen years. This investigation was prompted by clinical evidence of the radioresponsiveness of some prostatic cancers, the limited applicability of surgical excision, and the possibility that interstitial therapy would have less of an adverse effect on the quality of life than would alternative treatments. Cumulative experience indicates that the technique is associated with low morbidity and mortality and high functional preservation rates; local control rates (routine biopsies were not done), within the constraints of still-limited follow-up intervals, are in the 80 per cent to 90 per cent range; and actuarial survival rates at nine years (including patients who received endocrine therapy for metastatic or intractable local disease) are approximately 90 per cent for T1, 60 per cent for T2, and 45 per cent for T3 lesions. Approximate actuarial nine-year survival rates are 80 per cent for all patients with negative nodes and 50 per cent for all patients with positive nodes. Taking into account limitations of the data and the hazards of comparing this therapy with other uncontrolled treatments, 125I appears to be a therapeutic option for the control of clinically localized prostatic cancer. PMID- 2578698 TI - Protective effects of human gamma-globulin preparations against experimental aerosol infections of mice with Bordetella pertussis. AB - The protective effects of three types of pooled human gamma-globulin preparations (intact: GG, S-sulfonated: GGS, and pepsin-treated: GGP) for intravenous use against experimental aerosol infection of mice with Bordetella pertussis have been evaluated. The gamma-globulin preparations GG and GGS showed significant protective activity whereas GGP did not, as evaluated by survival numbers, body weight gains and suppression of leucocytosis. GG and GGS but not GGP also possessed neutralizing activity against leucocytosis-promoting and histamine sensitizing activities of pertussis toxin (PT). Evaluation of protective activities of GG, GGS and GGP prepared from rabbit gamma-globulin, highly immunized with PT and not containing any anti-F-HA (filamentous or agglutinin antibodies, demonstrated that anti-PT-GG and anti-PT-GGS but not anti-PT-GGP protected against experimental infection by B. pertussis. These studies showed that the protective activity was correlated with anti-PT titre but that the Fc portion of the gamma-globulin molecule is necessary for actual protection against whooping cough by B. pertussis. PMID- 2578699 TI - A monoclonal antibody labelling the keratinocyte membrane: a marker of epidermal differentiation. AB - A murine hybridoma secreting an IgM monoclonal antibody (KL3) was produced by cell fusion of mouse myeloma cells with spleen cells from mice immunized with human epidermal keratins. On normal human epidermis KL3 stained the intercellular spaces from the stratum germinatum to the stratum granulosum with a fluorescence intensity increasing from the basal layer to the upper layers. Basal cells were not stained on the side facing the basement membrane. About 90% of free keratinocytes isolated after trypsinization were labelled by KL3 in a punctate staining. Immunoelectron microscopy allowed us to show that the antigen recognized by KL3 was exclusively localized on the keratinocyte membrane especially in the desmosomal plaques. KL3 reactivity was not modified by preincubation of skin sections with lectins showing a selective intercellular labelling of upper layers of epidermis or pemphigus antisera, nor by adsorption of the antibody on NP40 soluble proteins of the epidermis. Though KL3 reactivity was completely abolished after adsorption of purified keratins, no immunological reactivity of KL3 was detected with epidermal keratin polypeptides blotted on nitrocellulose paper. In psoriatic epidemis and epidermal tumors KL3 reactivity was drastically modified. These results suggest that KL3 recognized a keratinocyte membrane antigen implied in the epidermal differentiation process. PMID- 2578701 TI - Promotion of palmar sweating with oral phosphatidylcholine. AB - Since acetylcholine is the main neurotransmitter of eccrine sweating, phosphatidylcholine ingestion might increase sweating. In 10 adults mid-palmar sweating was measured 12 hours after ingestion of a high and a low phosphatidylcholine supper. In a double blind, crossover study, mid-palmar sweating was measured in 11 consenting adults 12 hours after a low phosphatidylcholine supper taken with either lecithin or placebo. Five minutes after cleaning the palm and drying, sweat was captured in a quick-drying plastic film. The film was removed with cellophane tape and placed on a glass slide. Mean "droplet" diameter was measured by averaging the greatest diameter of 25 "droplets." Ten of 10 subjects (100%) produced more sweat with a high phosphatidylcholine meal than with a low one. Compared to placebo, 10 of 11 subjects (91%) given lecithin had significantly increased sweat secretion (p less than 0.01). It remains to be confirmed that this phosphatidylcholine-induced sweating increase is clinically significant. PMID- 2578700 TI - Immunoglobulin E in psoriasis evaluated by paper radioimmunosorbent and paper enzyme-immunosorbent tests. AB - Serum IgE concentrations were determined by the paper radioimmunosorbent test in 56 patients with psoriasis and 50 normal controls, and by the paper enzyme immunosorbent test in 32 of these patients and 50 controls. Elevated IgE levels were found in 26 (46%) of 56 patients with psoriasis and in 1 normal control (2%). The mean value (208 U/ml) in 56 patients was significantly higher than in normal controls (31 U/ml). Thirteen of 19 patients (68%) with extensive involvement (greater than 20% body surface) had an increased IgE level; the mean value (365 U/ml) was 4 times greater than in 17 patients with limited lesions (89 U/ml) and 12 times higher than in 50 normal controls (31 U/ml). No correlation was found between serum IgE levels and the presence of psoriatic arthritis. Both paper radioimmunosorbent and paper enzyme-immunosorbent testing produced similar results. PMID- 2578702 TI - Antinuclear antibodies in mice induced by long wave ultraviolet radiation (UVA). AB - PUVA therapy has been reported to induce antinuclear antibodies (ANA). The generation of ANA following ultraviolet irradiation was studied experimentally in albino mice. When treated with long wave ultraviolet radiation (UVA) from blacklight fluorescent tubes a significant number of animals developed positive ANA titres, whereas no change was noted in groups, treated with PUVA, 8 methoxypsoralen only or medium wave ultraviolet irradiation (UVB) respectively. The tendency for UVA-irradiated mice to develop ANA was stronger when higher ANA titres were compared. UVA induces ANA in mice, and PUVA-induced ANA may be due to the UVA component of this therapy. PMID- 2578703 TI - Antinuclear antibodies appearing during PUVA therapy. AB - Antinuclear antibodies (ANA) were studied in patients receiving PUVA therapy. Ten patients out of 124, (8%), considered for PUVA had ANA prior to therapy. During PUVA treatment ANA appeared in 34 out of 100 patients. Eight patients with ANA initially were treated and in 4 of them a significant increase in ANA titre was noted. A statistically significant difference was noted, when the first and last ANA tests for each patient were compared. No such difference was seen in a control group consisting of 33 patients. All PUVA patients generating ANA were evaluated clinically and with a laboratory screening. This evaluation was negative in all patients except one who developed ANA of the nucleolar staining pattern together with symptoms consistent with a collagen vascular disease. The ANA titres were generally low and the staining pattern was of the homogeneous type in all patients but one. PMID- 2578704 TI - Quantitation of contact allergy in guinea pigs by measuring changes in skin blood flow and skin fold thickness. AB - Skin blood flow determined by laser Doppler flowmetry (LDF) and skin fold thickness (SFT) have been used to quantitate allergic contact dermatitis in the guinea pig maximization test (GPMT) using chlorocresol as the allergen. The closed patch test procedure itself influenced both LDF and SFT measurements when determined in 12 sham-treated guinea pigs. The LDF was maximal at 24 hours and the SFT at 48 hours. Before correlating the quantitative measurements with the conventional visual scoring in test and control animals the value from a nearby control site was subtracted from the test site values. The correlations were highly significant (p less than 0.001-0.05) indicating that the quantitative methods were useful supplements to the visual scoring as a measure of interobserver and interlaboratory differences. PMID- 2578705 TI - Clinical manifestations of erythema chronicum migrans Afzelius in 161 patients. A comparison with Lyme disease. AB - Clinical symptoms were studied in 161 consecutive patients with erythema chronicum migrans Afzelius and in a follow-up study signs of late manifestations were investigated. General symptoms such as headache, fever, myalgia and/or arthralgia were found in about half of the patients with a disease duration of less than or equal to 3 weeks. Three patients had coexisting lymphadenosis benigna cutis. Two untreated patients developed meningitis/meningoradiculitis and one untreated patient arthritis. The importance of a sufficient antibiotic therapy to prevent late manifestations is stressed. Although there are many similarities between erythema chronicum migrans Afzelius and Lyme disease, the results of the present study also point to differences. Multiple skin lesions, pronounced general symptoms, laboratory abnormalities and major symptoms from the joints were less common in patients with erythema chronicum migrans Afzelius than reported in patients with Lyme disease, but a prolonged course of the skin eruption was more common. PMID- 2578706 TI - Topical nitrogen mustard in early mycosis fungoides. A 12-year experience. AB - A 12-year experience in thirty-three patients suffering from early mycosis fungoides in plaque stage confirms the effectiveness of topical nitrogen mustard therapy. Fourteen patients were in complete remission at the latest time of observation and 7 in partial remission. The probability of freedom from relapse was approximately 50% after 6 and 12 years. Three deaths attributable to mycosis fungoides were recorded. Three patients had to discontinue treatment due to contact dermatitis to nitrogen mustard. Specific precautions were undertaken in order to protect personnel handling the drug. No damaging or toxic effects were observed among staff personnel and no hematological side-effects were observed among the patients. The treatment as a whole was well tolerated. PMID- 2578708 TI - Increase of mast cells in the alopecia lesion of mice. AB - A histological investigation was made of the quantitative behavior of mast cells in bald areas on mice and in human alopecia areata. C57BL,W/Wv and +/+ mice with alopecia lesions were examined. In C57BL mice and +/+ mice, the number of dermal mast cells (per square mm) in the bald areas was greater than that in controls. The mean number of mast cells was slightly higher in human alopecia areata than in the controls. Since W/Wv mice lacking mast cells developed alopecia lesions, it seems that mast cells are not necessary for the onset of alopecia areata but could play some part in regrowth. PMID- 2578707 TI - Oral acyclovir suppression of recurrent genital herpes: a double-blind, placebo controlled, crossover study. AB - A randomised, double-blind, placebo-controlled, crossover study was conducted in 31 male patients with a history of frequently recurrent genital herpes who received consecutively 200 mg acyclovir and matching placebo by mouth four times a day for 12 weeks each. During acyclovir therapy recurrences were completely prevented in 24 (77%) and were reduced in both frequency and duration in the remainder compared with those occurring during treatment with placebo. The incidence and nature of adverse events reported during each treatment period was virtually identical. No long-term effects on recurrence rates were discernible but chronic suppressive therapy can be considered to offer the means of controlling the severe forms of disease experienced by some patients. PMID- 2578709 TI - Macromelanosomes in X-linked ocular albinism (XLOA). AB - A case of X-linked ocular albinism is reported. Characteristic Masson-Fontana positive and Dopa positive giant melanin granules were found in keratinocytes, melanocytes and upper dermis. Ultrastructurally the macromelanosome was composed of a dense core and a less dense surrounding mantle. PMID- 2578710 TI - Retinoid dermatitis mimicking progression in mycosis fungoides: a report from the Scandinavian Mycosis Fungoides Group. AB - A dermatitis occurring during the treatment of mycosis fungoides with A vitamin analogues (13-cis-retinoic acid and etretinate) and mimicking a progression of the disease is described. It is considered to be a skin reaction due to the treatment. Its benign nature is revealed by histology showing a lymphocytic infiltrate without any atypical sign. PMID- 2578711 TI - Recurrent cutaneous jellyfish eruptions without envenomation. AB - Three patients exhibiting recurrent cutaneous eruptions induced by contact with jellyfish tentacles are presented. The recurrent eruptions appeared several days after the primary exposure without contact with any offending coelenterate. The principal species involved include Pelagia noctiluca, Physalia physalis and probably Lychnorhiza lucerna. These three cases, combined with an earlier similar report of recurrent lesions induced by Physalia physalis suggest that this phenomenon may be widespread. In two of the three cases, the secondary eruption was more severe than that occurring after the primary envenomation. PMID- 2578712 TI - The Klippel-Trenaunay syndrome with acro-angiodermatitis (pseudo-Kaposi's sarcoma). AB - A patient with the Klippel-Trenaunay syndrome and pseudo-Kaposi elements is reported. This combination of symptoms has only been published very occasionally. Selective quantitative measurements of the peripheral tissue blood flow revealed a significantly increased cutaneous blood flow in the hypertrophied leg. This finding supports the assumption that a high perfusion rate and a high oxygen saturation are involved in the etiopathogenesis of the pseudo-Kaposi elements. PMID- 2578713 TI - Sweet's syndrome and pyoderma gangrenosum associated with ulcerative colitis. AB - A young woman with ulcerative colitis developed pyoderma gangrenosum during the active phase of the disease and Sweet's syndrome (acute febrile neutrophilic dermatosis) three months after panproctocolectomy. PMID- 2578714 TI - Diffuse fasciitis with eosinophilia associated with morphea and lichen sclerosus et atrophicus. AB - Diffuse fasciitis with eosinophilia (DFE) is a well described syndrome, among the connective tissue disorders. However, DFE is not commonly accepted as an own entity, because of its rare evolvement in scleroderma and the often indistinguishable histological pattern of both diseases. Here we report on the association of DFE and morphea in two patients and an additional lichen sclerosus in one of them. This points to a close relationship of DFE and other connective tissue diseases. PMID- 2578715 TI - Radiographic bone surveys after isotretinoin therapy for cystic acne. AB - Seven patients underwent retrospective radiographic examination 10 to 16 months after high dose isotretinoin therapy for severe cystic acne. One patient, who received the highest isotretinoin dose (approximately twice the average dose taken by the remaining patients), had multiple small hyperostoses of the thoracic spine and tarsi navicular. These findings were identical to the skeletal changes known to occur during retinoid administration. Prospective studies are needed to ascertain the risk of developing hyperostoses during isotretinoin therapy for acne at the lower doses currently employed. In this preliminary study, clinically significant hyperostoses were not a late sequela of high dose isotretinoin treatment for acne. PMID- 2578716 TI - Comparison of trioxsalen bath and oral methoxsalen PUVA in psoriasis. AB - Fifty patients with chronic plaque psoriasis were treated with trioxsalen bath PUVA and 43 patients with oral methoxsalen PUVA. The two treatment regimens gave similar results; 75% and 77% of the patients had excellent or good clearing and a follow-up of one year revealed relapses in 61% and 58% of the patients, respectively. The cumulative UVA dose remained significantly lower in bath PUVA (mean 23.5 J/cm2) than in oral PUVA (mean 131 J/cm2). Nausea and headache occurred in 21% of the patients receiving oral PUVA but in none in the bath PUVA group. Local side-effects were found in 30% of the patients receiving bath PUVA and in 17% of the patients in the oral PUVA group. PMID- 2578717 TI - Increased sensitivity of the fluorescent treponemal antibody absorption test with biotin/avidin: a comparison with conventional FTA-ABS. AB - The biotin/avidin system was adapted to the FTA technique for detection of IgG, IgM, and IgA antibodies specific to Treponema pallidum. By using biotin/avidin IgG antibodies could be detected in a serum dilution 15 000 times higher, and IgM 3 000 times higher than was possible with conventional FTA technique. IgA antibodies, however, were not detected with any of the methods. PMID- 2578718 TI - HLA-DR-antigen bearing keratinocytes in various dermatologic disorders. AB - In normal human epidermis HLA-DR-antigen is only present on Langerhans' cells and the acrosyringeal epithelium. We investigated the distribution of HLA-DR-antigen in 78 specimens of various skin diseases by an immunoperoxidase method using a monoclonal anti-HLA-DR antibody. HLA-DR-antigen bearing keratinocytes were not only found in lichen planus and mycosis fungoides, as it has been referred previously, but were also observed in some cases of cutaneous B-cell lymphoma, pseudolymphoma, lupus erythematosus, parapsoriasis en plaque, bullous pemphigoid, drug reaction, contact dermatitis, actinic keratosis and verrucous carcinoma. Direct contact of lymphoid cells with keratinocytes was not necessary for Ia antigen expression. PMID- 2578719 TI - Long-term culture of differentiated human thyroid tissue. AB - Human thyroid cells obtained during surgery have been maintained in monolayer culture for at least 2 months and without loss of morphological or functional differentiation. Samples as small as 0.5 g could be cultured but best results were obtained with samples of 5-10 g. The technique used was developed in this laboratory for sheep tissue and was applicable without significant modification to human tissue. It depends on the complete absence of media changes at any time during the culture period. Energy substrates are replenished by the addition of concentrated glucose solutions to the existing media at carefully monitored intervals. Differences in both morphology and function could be observed between cultures derived from patients with different diseases, suggesting that the technique could have predictive value. PMID- 2578720 TI - Effects of insulin-like growth factors on chick embryo hepatocytes. AB - Biological effects of insulin-like growth factors (IGF) I and II on primary cultures of chick embryo liver cells have been investigated and compared 1) with the biological effect of insulin and 2) with competitive binding of the three hormones to their respective binding sites. IGF I and II stimulate the incorporation of D[U-14C]-glucose into liver cell glycogen in a time- and dose dependent manner, but with a 5-10-fold lower potency than insulin. Both IGFs also lead to enhanced incorporation of 5-[3H]uridine and L[U-14C]valine into trichloroacetic acid (TCA) insoluble material and to activation of ornithine decarboxylase activity. Their potency in stimulating RNA synthesis and ornithine decarboxylase activity is comparable to that of insulin. Protein synthesis is maximally stimulated at 3 nM by all three hormones. In the competitive binding studies, IGF I and II are 10-fold less potent than insulin in competing for [125I]insulin binding, but 100-fold more potent than insulin in competing for [125I]IGF I or II binding. These studies show that IGF I and II stimulate the same metabolic indices as insulin in the chick embryo liver. By comparing these biological effects with competitive binding data it appears that IGFs act on glucose metabolism in the chick embryo liver via the insulin receptor, whereas stimulation of growth indices by IGFs and insulin appears to be mediated by their own specific receptors. PMID- 2578722 TI - Some effects of the calcium promotor BAY K 8644 on feline cerebral arteries. AB - The proposed calcium promotor BAY K 86(44) contracted feline basilar arteries partially depolarized by 10 mmol X 1(-1) potassium in a concentration-dependent manner (EC50 value: (2.1 +/- 1.2) X 10(-9) mol X 1(-1)). The concentration response curve for prostaglandin (PG) F2 alpha was displaced to the left after pretreatment with BAY K 86(44). PGF2 alpha induced a biphasic contraction in calcium-free medium as has been described previously. The second PGF2 alpha induced contraction phase in calcium-free medium was abolished by pretreatment with nifedipine or diltiazem. BAY K 86(44) restored the second phase in arteries pretreated with nifedipine, but not in vessels pretreated with diltiazem. The findings suggest that BAY K 86(44) acts as a promotor of calcium-influx, probably by interaction with the 'dihydropyridine receptor' in the cell membrane, and also provide support for the view that PGF2 alpha releases membrane-bound calcium. PMID- 2578721 TI - Effect of proteinase inhibitors on rabbit uterine ultrastructure. AB - Rabbit uterine epithelium was examined by electron microscopy after treatment with two proteinase inhibitors, aprotinin and antipain, administered as a single injection. Both compounds had similar effects, those of antipain being slighter. After treatment, uterine epithelium showed an increased number of very enlarged cells. Lateral cell membranes were often brocken off; basal cell membrane and basement membrane integrities are impaired. The possible interference of the system proteinase-proteinase inhibitors with the implantation process was discussed. PMID- 2578723 TI - Insulin potentiates cholecystokinin (CCK)-induced secretion of pancreatic kallikrein. AB - The effects of insulin on pancreatic kallikrein secretion were studied in streptozotocin diabetic rats and after acute administration of insulin to normal rats. Studies on total protein and amylase secretion were included for comparison. In diabetic rats, the concentration of amylase in pancreatic tissue as well as basal and CCK-stimulated amylase exocrine secretion were significantly reduced. Insulin treatment restored pancreatic tissue concentration and exocrine release of amylase to normal. Insulin deficiency did not induce any change in the concentration of kallikrein or trypsin-like activity in pancreatic tissue. However, basal kallikrein secretion was higher in diabetic rats than in controls. Insulin treatment of diabetics rats did not alter basal kallikrein secretion but potentiated CCK-stimulation of kallikrein release. In normal rats, CCK induced an increase of pancreatic protein, amylase, and kallikrein secretion but not pancreatic juice flow. Additional administration of insulin potentiated the CCK induced secretory rate of pancreatic juice, protein, and kallikrein but not amylase. A 1.6 times higher concentration of kallikrein was found in the portal vein than in arterial blood, indicating an endocrine release of pancreatic kallikrein. No difference in the concentration of circulating kallikrein was observed between the control and the insulin-treated group. PMID- 2578724 TI - Calcium-channel blockers: effects on cerebral blood flow and potential uses for acute stroke. AB - Current research suggests that ischemia induces a massive shift of calcium from the extracellular fluid to the intracellular space. This is associated with a precipitous decrease in the concentration of adenosine triphosphate, the energy source required to drive the ion pumps of the calcium channels that maintain intracellular calcium homeostasis. The result is a further increase in free intracellular calcium, leading to calcium overload and thus to cell catabolism and cell necrosis. Treatment with calcium-channel blockers may therefore offer a new approach to arresting and, possibly, preventing destruction of cerebral tissue in stroke victims. Animal studies using nimodipine, a calcium antagonist with marked vasodilator effects, have shown that this agent prevents both spasm of the isolated rabbit basilar artery, produced either by depolarization or by receptor stimulation, and postischemic impairment of cerebral blood flow (CBF), which may be a major contributor to neuronal damage. In patients with acute ischemic stroke, intravenous nimodipine therapy caused a dose-dependent increase in hemispheric CBF. These data prompted us to conduct a prospective, single blind, randomized trial of 60 patients to determine whether nimodipine treatment would reduce neurologic deficits in patients with acute ischemic stroke. The 29 treated patients were given standard dextran therapy supplemented with daily 120 mg doses of nimodipine, and the 31 control subjects received dextran therapy alone. Mathew scale neurologic scores indicated decreased consciousness and impaired cerebral function in both treated and control groups; however, cerebral deficits were significantly smaller in patients who received nimodipine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578725 TI - Basic cellular mechanisms of action of the calcium-channel blockers. AB - Calcium-channel blockers inhibit the entry of calcium ion (Ca++) into excitable cells, including those of coronary and peripheral arterial smooth muscle and the heart. The ability of these drugs to block Ca++ entry into cells inhibits the essential role of this cation as an intracellular messenger. The effects of calcium-channel blockers on the heart include a negative inotropic effect on the working myocardial cells of the atria and ventricles. Because the up-stroke of the action potential in these regions of the heart, and in the rapidly conducting cells of the His-Purkinje system, is due to a fast, sodium-dependent ionic current, calcium-channel blockers do not inhibit conduction in these cells. In the sinoatrial and atrioventricular (AV) nodes, on the other hand, depolarization is due primarily to a Ca++-dependent slow inward current; as a result, the calcium-channel blockers inhibit the sinus pacemaker and AV conduction. Because our knowledge of the molecular structure of the calcium channels in the heart and smooth muscle is rudimentary, little is known of the molecular mechanisms by which calcium-channel blockers inhibit Ca++ entry across the sarcolemmal membranes in these cells. It is apparent, however, that the actions of different members of this class of drugs on the sarcolemma are not the same. Indirect evidence indicates that some members of this class of drugs may interact with hydrophobic regions of the proteins that make up, or regulate, the calcium channels in the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578726 TI - A comparative study of osteoblasts: in situ versus isolated specimens. AB - Osteoblasts and osteoclasts are known to adhere tenaciously to bone surfaces even when the fibrous periosteal covering is removed. Brush-smear isolates and in situ, whole bone mounts of the osteogenic periosteum on the inner and outer calvarial tables of young adult rats were examined at the light microscopic level after exposing the cells by removing the fibrous periosteum. Based on staining, enzymatic activity, and overall morphology, most of the cells could be classified as osteogenic in nature. However, detailed analysis revealed that some cells exhibited certain unique morphologic appearances that suggested the existence of subpopulations or variant forms of the conventional or prototypic osteoblast. Three variant forms were the large nucleate, small nucleate, and multinucleate osteoblast-like cells, the latter with nuclear numbers ranging from 2-10. The finding of all such forms in smears, short-term cell cultures, and in situ specimens greatly lessened the probability that the unusual forms were artifactual. Phase contrast microscopic studies and sectioning of cellular isolates for study at both the light and electron microscopic levels provided additional support for the existence of the multinucleate osteoblast-like cell. The small size of these osteoblast-like subpopulations and the orientation of the cells to the commonly used plane of section of most histologic bone specimens, particularly with the multinucleate type, could explain why they had escaped earlier detection. PMID- 2578728 TI - Immunohistochemistry as an aid in the diagnosis of Hirschsprung's disease. AB - The interpretation of rectal suction mucosal biopsies taken for the purpose of ruling out Hirschsprung's disease (HD) can be especially difficult in neonatal patients because of ganglion cell (GC) immaturity. Acetylcholinesterase histochemistry on frozen sections can be helpful but requires experience and may be complicated by excessive mucosal hemorrhage. The authors retrospectively have studied 27 patients, including 11 patients with HD, on whom conventionally fixed and embedded tissue was available, using an immunoperoxidase system directed against neuron-specific enolase (NSE) and S100 protein. NSE immunostaining produced intense staining of GC perikarya, greatly facilitating recognition of small immature forms. S100 immunostaining also highlighted GC as prominent negative stained cells surrounded by the positivity of Schwann cells. Both stains were helpful in demonstrating the overall pattern of microinnervation and its relationship to possible GC. The authors conclude that NSE and S100 immunostaining may facilitate interpretation of rectal mucosal biopsies when Hirschsprung's disease is being considered as a possibility. PMID- 2578727 TI - Anaplastic thyroid carcinoma. A study of 70 cases. AB - Seventy cases of anaplastic thyroid carcinomas studied at the Universities of Florence (Italy) and Minnesota are presented. Three morphologic patterns were seen: spindle, giant cell, and squamoid, sometimes in combination. Ultrastructurally, evidence of epithelial differentiation was seen in most but not all cases studied. Immunohistochemically, a stain for cytokeratin using a monoclonal antibody was found the most useful adjunct to diagnosis. Unexpected positivity for carcinoembryonic antigen (CEA) was found in several squamoid tumors. The alleged frequent positivity of this tumor type for thyroglobulin and calcitonin was not confirmed. A third of the tumors were associated with a better differentiated component, of which, presumably, they represented a dedifferentiation. The extremely aggressive behavior of anaplastic thyroid carcinomas was confirmed amply in this series: all of the patients in whom follow up information was available died of their tumor. Small cell tumors should not be included into the anaplastic category, since they invariably belong to other groups, i.e., malignant lymphoma, medullary carcinoma, and poorly differentiated ("insular") carcinoma. PMID- 2578729 TI - The pathogenesis of pancreatic pseudocysts--a canine experimental model. AB - In summary, an experimental model that mimics the pseudocyst formation in man was produced in dogs. The following conditions were met: encapsulated cyst containing pancreatic juice; an actively secreting pancreas with hyperamylasemia and pancreatitis; a ductal communication; and more pronounced effects with partial pancreatic ductal obstruction. PMID- 2578730 TI - Some studies with a monoclonal antibody directed against human fibrinogen. AB - Some properties of a monoclonal antibody generated against the fibrinogen component of a factor VIII preparation were investigated. The antibody bound with equal affinity in solid phase radioimmunoassays to fibrinogens isolated from both normal patients and patients with von Willebrand disease. It reacted in a sensitive immunoassay of plasma fibrinogen. The specificity of the antibody was confined to the parent molecule with no significant inhibition of fibrinogen binding by the fibrinogen degradation products (FDPs) X, Y, D, or E. The antibody had no significant effect on the activated partial thromboplastin time and prothrombin time of normal plasma. However, it prolonged the thrombin time as determined by the Clauss chronometric fibrinogen method. During fibrinogen lysis by plasmin immunoreactivity of fibrinogen to the antibody was lost at the same rate as the clottable fibrinogen content determined by the Clauss assay. The lack of reactivity of the antibody with FDPs makes it a suitable reagent for investigating plasmin activity as well as studying fibrinogen and fibrin. These findings suggest that the epitope of the antibody lies within the polar protruberance of the carboxy terminal end of the A alpha chain of fibrinogen and is destroyed by plasmin cleavage. PMID- 2578731 TI - Pseudouremic pruritus: a scabies epidemic in a dialysis unit. AB - A scabies epidemic was studied in a university hospital dialysis unit. Itching in patients was initially attributed to uremic pruritus, and diagnosis of the epidemic was delayed until cases occurred among the staff. Sixteen cases (seven patients and nine staff) were identified by survey questionnaire and dermatologic examination. Application of 1% lindane lotion (Kwell, Reed and Carnrick, Piscataway, NJ) to all patients dialyzed in the unit and the entire staff eradicated the epidemic. A dialysis unit-associated nosocomial scabies epidemic has not been reported before and may mimic uremic pruritus in dialysis patients. PMID- 2578732 TI - Implications of new technology for pharmacy education and practice. AB - Specific knowledge and skills needed by pharmacists in an era of advancing health care technology are presented, and the most important modern technologic developments in health care are described briefly. Implementation of new technology in health care will be affected by cost considerations and by social trends such as shifting population demographics, an increase in diseases of lifestyle, consumerism, and self-care. Technologic advances in the following areas are described: computerized information networks, bioelectronics, biotechnology, computer graphics, diagnostic imaging, and drug development in space and in the oceans. Diseases are noted for which diagnosis and treatment using new technology is promising. The roles of interferon and monoclonal antibodies are described, and trends in development of new drugs and drug delivery systems are traced. A new philosophical basis for pharmacy education that is consistent with the needs of a technologically oriented society is needed. Practitioners will look to their professional societies for assistance in identifying and implementing the new technology. PMID- 2578734 TI - The harmful effects of ethanol on ion transport and cellular respiration. AB - The deleterious effects of ethanol on a variety of tissues may result largely from altered ion permeabilities and transport. Clinically relevant ethanol concentrations in blood increase the sodium permeability of the plasma membrane and depress active sodium transport by suppressing Na, K-ATPase activity. As a result, intracellular sodium concentration increases. The total tissue content of calcium increases. Important transport mechanisms deranged by ethanol probably include those regulating calcium-sodium and hydrogen-sodium exchange at the plasma membrane and calcium uptake by the sarcoplasmic reticulum. A modest decline in magnesium content of muscle occurs after chronic exposure to ethanol. This also has been associated with accumulation of calcium. After days to weeks of sustained ethanol intake, sodium pump activity, active sodium transport and tissue oxygen consumption increase. The cell membrane potential, initially lowered by alcohol, increases to supraphysiological levels. This is likely an electrogenic effect of increased sodium transport in response to a sodium leak. Eventually the earlier derangements in tissue composition, including retention of sodium, chloride, and calcium, and reductions in magnesium, potassium, and phosphate, slowly undergo correction. This biphasic response of injury and adaptation appears to depend upon adequate nutrition and the absence of other factors that can adversely affect cell function. That the Na, K-ATPase activity and oxygen consumption remain elevated suggests an ongoing sodium leak of the sarcolemmal membrane. Chronic ethanol-induced cell necrosis may be related to the increased intracellular calcium that accompanies the increase in sodium permeability. Conceivably, critically elevated concentrations of calcium in the cytoplasm may activate autolytic enzymes that in turn may be responsible for structural damage to the cell. PMID- 2578735 TI - The bleak outlook on ovarian cancer. PMID- 2578733 TI - Investigation into the immunologic cross-reactivity of aztreonam with other beta lactam antibiotics. AB - The cross-reactivity between the monobactam antibiotic aztreonam and the commonly used beta-lactam antibiotics, penicillins, and cephalosporins was investigated. Antibodies to aztreonam, penicillin, and cephalothin were raised in rabbits. The ability of the homologous or heterologous drug or drug conjugates to inhibit antibody binding was assessed in a solid-phase radioimmunoassay. Aztreonam demonstrated very little ability to interact with anti-penicillin or anti cephalothin antibodies as it required 10,000-fold higher concentrations than other beta-lactams to achieve equivalent blocking. Similarly, penicillin and cephalothin conjugates did not cross-react, to any significant degree, with anti aztreonam rabbit antiserums. Interestingly, free aztreonam was as effective as conjugated aztreonam in reacting with antibodies raised against conjugated aztreonam. This result suggested that, in contrast to the other beta-lactams, antibodies to aztreonam recognize the side chain rather than the nuclear structures. Studies with other beta-lactam analogs confirmed that the IgG rabbit anti-aztreonam binding was indeed side chain-specific. Thirty-six volunteers were given a seven-day course of therapeutic doses of aztreonam and in none did any detectable IgE anti-aztreonam antibodies develop. Four of these subjects had evidence of preexisting IgG antibodies cross-reactive with aztreonam, but the levels rose in only one patient following drug exposure. This human IgG anti aztreonam was also directed to the side chain and did not cross-react with cephalothin or penicillin. The ability of aztreonam to cross-react with human IgE to various penicillin determinants was also investigated. Aztreonam determinants analogous to the penicillin determinants (penicillin, penicilloyl, and penicilloate) were constructed and the maximal concentration that did not evoke false-positive skin test results was determined to be 6 X 10(-3) mol/liter. None of 41 patients with documented IgE-reactive skin tests to various penicillin determinants concurrently demonstrated reproducible reactivity to any aztreonam reagents. IgE anti-penicilloyl antibodies from three persons were also tested in vitro for their ability to cross-react with conjugated or free aztreonam. Minimal, if any, reactivity was observed between the IgE anti-penicilloyl and any of the aztreonam materials. These results indicate that there is very little cross-reactivity between the monobactam aztreonam and other beta-lactam antibiotics. PMID- 2578736 TI - Delayed choroidal vascular filling after krypton laser photocoagulation. AB - In four patients treated for macular subretinal neovascularization with krypton red laser photocoagulation, follow-up fluorescein angiograms performed two to ten days after treatment showed wedge-shaped areas of delayed choroidal vascular filling adjacent to and extending directly from the treated areas. There were no immediate or late changes in the fundus corresponding to the areas of delayed choroidal vascular filling. Goldmann visual fields done on two of the patients showed no functional deficit corresponding to the areas of delayed filling. Deep choroidal energy absorption of the krypton wavelength causing choroidal vessel thrombosis could explain this complication. PMID- 2578737 TI - Optic disk neovascularization in leukemia. PMID- 2578738 TI - Culturing of human hepatocellular carcinoma. A simple and reproducible method. AB - Eight permanent human hepatocellular carcinoma (HHC) cell lines were established from 8 individual patients by the use of aspirated needle biopsy specimens (smaller than 0.1 ml in size). The cells grew in clustered form and retained intercellular junctions and canaliculi resembling bile canaliculi. The presence of secreted human alpha-fetoprotein and human albumin was detected in the cultured medium. Hepatitis B surface (HBs) antigen was not found on these cells. Implantation of the cells into athymic mice was followed by the growth of hepatocellular carcinomas and the appearance of human alpha-fetoprotein in the mouse serum. Chromosome analysis of three of the cell lines showed hyperdiploidy in two of them and hypotetraploidy in the other. Enzyme analyses of culture medium and cell homogenates have detected some enzymes characteristic of liver tissue such as gamma-glutamyl transferase, sorbital dehydrogenase, alkaline phosphatase, glutamate dehydrogenase, as well as aspartate and alanine transaminase. These tumor cells have been continuously maintained in culture for over 6 years with no significant changes observed. PMID- 2578740 TI - Exchange of macromolecules between peritoneal cavity and plasma. AB - The exchange of fluorescein isothiocyanate-labeled dextrans ranging in weight averaged molecular weight from 19,400 to 160,000 and 125I-bovine serum albumin (BSA) between dialysis fluid (5% BSA in Krebs-Ringer solution) in the peritoneal cavity and the plasma was studied in anesthetized female Sprague-Dawley rats. Plasma and peritoneal samples were collected for 3-4 h after either 1) an intraperitoneal injection of dialysis fluid with tracer or 2) an intravenous injection of tracer material simultaneously with an intraperitoneal injection of dialysis solution without tracer. Analysis of the data by means of a mathematical model of the transport process suggests a functional asymmetry in transport of large molecules across the blood capillary wall. Substances injected intravenously have a net transport from the blood capillaries to the peritoneal cavity. Substances of molecular weight greater than or equal to 39,000 transport from the cavity to the plasma via peritoneal lymphatics; 19,400 molecular-weight dextran transports from the cavity to the plasma primarily via lymphatics with some blood capillary uptake. Tissue diffusivities and capillary mass transport coefficients are derived for the substances tested. PMID- 2578739 TI - Connection of ductlike structures induced by a chemical hepatocarcinogen to portal bile ducts in the rat liver detected by injection of bile ducts with a pigmented barium gelatin medium. AB - Newly found metaplastic ductlike structures that form in the liver of rats exposed to carcinogens are connected to preexisting bile ducts. Male Fischer rats fed a diet of N-2-acetylaminofluorene in a choline-deficient diet (CDAAF) develop a massive proliferation of oval cells which appear to differentiate into bile ductlike structures. However, unlike normal or proliferating bile ducts, these ductlike structures contain alpha-fetoprotein (AFP) and albumin, which are markers for proliferating hepatocytes and some hepatocellular carcinomas. Bile duct injections with a green pigmented barium gelatin medium filled the lumens of the ductlike structures and typical ductlike structures induced by the CDAAF diet, as well as the proliferating bile ducts induced by the noncarcinogenic alpha-naphthylisothiocyanate (ANIT), and the ducts in the normal controls. AFP was present in the ductlike structures in the rats fed AAF, but not in the bile ducts of animals fed ANIT. These studies suggest that most, if not all, of the ductlike structures produced during chemical hepatocarcinogenesis are derived from bile ducts, yet have the capacity to produce AFP and albumin. PMID- 2578741 TI - Lung growth in response to unilateral pneumonectomy in rapidly growing rats. AB - The rapidity with which lung growth is initiated and completed after pneumonectomy was examined in young rats (4 wk of age; 82 g). After left pneumonectomy, the remaining lobes of the right lung grew to equal the weight of both lungs of control animals by day 7 and within 14 days increased from 366 to 968 mg. The tissue concentrations of RNA, DNA phosphate, collagen, and noncollagen proteins did not increase during the growth response. In contrast, total amounts of these constituents increased significantly in the remaining lung of pneumonectomized animals during the 1st postoperative wk and approached levels found in both lungs of sham-operated and unoperated controls by the end of the 2nd wk after pneumonectomy. Although cell size increased in control lungs during the experimental period, there was little evidence of additional cellular hypertrophy associated with compensatory lung growth. The character of the response to pneumonectomy in these rats was similar to that observed previously in older animals (320 g). Thus in spite of the higher basal rate of lung growth in the younger rats, the pattern and rapidity of compensation after pneumonectomy was similar in both age groups. PMID- 2578742 TI - Compensatory adrenal cortical growth is inhibited by sympathectomy. AB - After the surgical removal of one adrenal gland, the cortex of the remaining adrenal gland increases in size. This compensatory adrenal growth is characterized by increased weight and DNA content of the remaining adrenal 72 h after unilateral adrenalectomy. In these experiments, chemical sympathectomy prevented compensatory adrenal growth. In rats sympathectomized by neonatal injections of 6-hydroxydopamine or guanethidine and unilaterally adrenalectomized at 40 days of age, the compensatory increase in weight in the remaining gland was attenuated (relative to a vehicle-injected control group) and not accompanied by the usual increase in DNA content. Augmented RNA content was observed after unilateral adrenalectomy in sympathectomized as well as vehicle-injected animals; presumably this reflects increased steroidogenesis because, despite the loss of one adrenal, the rats maintained normal plasma corticosterone and aldosterone levels (relative to the sham-adrenalectomized group). The sympathectomy procedures themselves did not significantly alter adrenal weight, adrenal nucleic acid content, or plasma aldosterone relative to vehicle-injected control levels; however, plasma corticosterone levels were significantly reduced. We conclude that the sympathetic nervous system mediates the adrenal cortical cell proliferation that occurs after unilateral adrenalectomy. PMID- 2578743 TI - Nicotine stimulation of protein secretion from isolated rat pancreatic acini. AB - The secretion of amylase and trypsinogen from isolated rat pancreatic acini was greatly stimulated by 3-25 mM nicotine. In the presence of 12.5 mM nicotine, a concentration used in the study, amylase and trypsinogen release was increased by 95 and 400%, respectively, when compared with the corresponding control and showed further a preferential release of trypsinogen. A 90-min time course release of the enzymes revealed that in the presence of nicotine trypsinogen-to amylase ratio remained two- to threefold elevated over that of the control throughout the incubation period. The nicotine-induced stimulation of trypsinogen and amylase release from the acini could not be blocked by 2.5 mM cycloheximide, a dose that inhibited overall acinar protein synthesis by about 85%. When isolated acini were incubated with [3H]leucine in the presence of nicotine, the released proteins revealed a fourfold higher radioactivity (dpm/microgram acinar DNA) than the control. Cycloheximide dramatically decreased this increment. The rate of release of 3H-pulse-labeled proteins from the acini was greatly accelerated by nicotine. It is concluded that nicotine stimulates the secretion of preformed zymogen granules and newly synthesized proteins from dispersed rat pancreatic acini in vitro. PMID- 2578744 TI - Bombesin-induced residual stimulation of amylase release from mouse pancreatic acini. AB - When dispersed acini from mouse pancreas are first incubated with bombesin, washed, and then reincubated with fresh incubation solution containing no bombesin, there is significant residual stimulation of amylase release. Induction of residual stimulation is relatively rapid in that significant stimulation occurs as early as after 15 s of first incubation with bombesin. Induction of residual stimulation of amylase release per se is temperature independent, but induction does occur more rapidly when acini are first incubated at 37 degrees C than when they are first incubated at 4 degrees C. Residual stimulation of amylase release persists for at least 75 min in acini that have been first incubated with bombesin at 37 degrees C. The maximal residual stimulation of amylase release obtained with pancreatic acini that have been first incubated with bombesin and then washed is 45% greater than the maximal stimulation obtained when bombesin is added directly to the incubation medium. In terms of their abilities to cause residual stimulation of amylase release, litorin and ranatensin are equal to bombesin in potency and efficacy. Gastrin-releasing peptide is approximately 70% as efficacious as bombesin in causing residual stimulation of amylase release. PMID- 2578745 TI - Omeprazole inhibits H+ secretion by Amphiuma jejunum. AB - The effect on HCO3- absorption of the substituted benzimidazole omeprazole, an inhibitor of active H+-K+ exchange, was examined in in vitro Amphiuma jejunum. HCO-3 absorption was measured using titration in short-circuited intestinal segments bathed in a Cl--free (SO2-(4)-based) medium (pH 7.40). At 1 mM omeprazole lowered the short-circuit current (Isc) and the absorptive flux of HCO3- from mucosa to serosa by about 40% over 1 h. When the serosal medium was maintained at pH 5.0, additions of omeprazole beginning at 0.1 mM caused proportional reductions of the Isc. Omeprazole also reduced intracellular potassium activity (aiK) from 74 to 59 mM and lowered the luminal membrane potential (psi m) slightly over 30 min when this was measured with double barreled, K+-sensitive microelectrodes. After 30 min aiK and psi m tended to spontaneously revert toward control values. Galactose added to the mucosal medium (to 20 mM) stimulated the Isc equally in omeprazole-treated tissues and paired untreated control tissues. These results support the view that a fraction of the absorptive HCO3- flux (so-called) is driven by an active luminal exchange of H+ for K+. PMID- 2578746 TI - A search for interferon in the CSF of chronic schizophrenic patients. PMID- 2578747 TI - Duodenal gangliocytic paraganglioma. An immunohistochemical and ultrastructural study and a hypothesis concerning its origin. AB - We report the immunohistochemical and ultrastructural features of three duodenal gangliocytic paragangliomas and compare them with duodenal carcinoid, extra adrenal paraganglioma, pheochromocytoma, and ganglioneuroma. The gangliocytic paraganglioma is characterized by polygonal or columnar epithelial cells, ganglion cells, and spindle cells. The epithelial cells stained for neurofilament, neuron-specific enolase, pancreatic polypeptide, and somatostatin in three cases; leu-enkephalin, molluskan cardioexcitatory peptide, and vasoactive intestinal peptide in two; and glucagon and insulin in one case each. The ganglion cells were positive for leu-enkephalin, neurofilament, neuron specific enolase, pancreatic polypeptide, and somatostatin in three cases, and glucagon in one. The spindle cells stained for neurofilament, neuron-specific enolase, and S-100 protein. Although there was some overlap in immunoreactivity between the gangliocytic paraganglioma and the other tumors examined, our data indicate that the gangliocytic paraganglioma is a distinctive lesion. We propose that it is a hyperplastic or neoplastic proliferation of 1) endodermally derived epithelial cells originating from the ventral primordium of the pancreas, 2) neuroectodermal ganglion cells, and 3) neuroectodermal spindle cells (Schwann cells). PMID- 2578748 TI - Malignant neuroendocrine tumor of the jejunum with osteoclast-like giant cells. Enzyme histochemistry distinguishes tumor cells from giant cells. AB - We report a case of a neuroendocrine tumor of the jejunum metastatic to the liver in a 26-year-old woman. Light and electron microscopy of this tumor revealed a poorly differentiated neoplasm composed of clusters of round to polygonal cells compatible with a diagnosis of neuroendocrine tumor. In the absence of identifiable silver-staining granules or immunocytochemical demonstration of a specific hormone product in tumor cells, this tumor cannot be further classified among the various neuroendocrine tumors that may arise in this location. However, interspersed among tumor cells was a distinct population of multinucleate giant cells having an appearance similar to benign osteoclasts. Enzyme histochemistry for 5'-nucleotidase, acid phosphatase, and nonspecific esterase each showed a dichotomous staining pattern for the small tumor cells and giant cells and suggest that the giant cells are not tumor derived, but represent a second, presumably reactive, cell population. PMID- 2578749 TI - Preparation of a new antivenin by affinity chromatography. AB - Polyacrylamide gel affinity chromatography was employed to isolate and purify antibodies to the antigens of the venoms of four rattlesnakes. The antivenins were studied for their neutralizing properties on a number of pharmacologic preparations. It was found that the purified antibodies (IgG) were more efficacious than the commercially prepared antivenin in neutralizing the lethal, cytolytic, hemorrhagic, platelet aggregating, and other deleterious effects of the venoms. In addition, the purified antibodies gave no evidence of producing anaphylaxis or anaphylactoid reactions in animals sensitized to horse serum. The proposed technique is also more simple than current production methods, is time saving, and less expensive. PMID- 2578750 TI - Epitopic analysis of antigenic determinants on the surface of dengue-2 virions using monoclonal antibodies. AB - The relative binding sites of dengue serotype-specific, dengue subcomplex specific, dengue complex-specific, flavivirus subgroup-reactive, and flavivirus group-reactive monoclonal antibody preparations were identified by using competitive antibody binding assays. A dengue complex-specific epitope, capable of mediating infection enhancement, was identified on a 20,000 dalton protein found on intracellular virions. The other epitopes were assigned relative positions on the E glycoprotein by competitive antibody binding. These could be grouped into 3 linkage groups based on the ability of some monoclonal antibodies to block contiguous binding sites. Some antibodies were able to increase or "promote" the binding of antibodies from other linkage groups. These results suggest that a continuum of antigenic reactivities exist on the E glycoprotein of the dengue viruses, and that the conformation of this glycoprotein may be altered after antibody binding. PMID- 2578751 TI - Laveran's germ: the reception and use of a medical discovery. AB - The research efforts to identify the etiological agent of malarial fevers during the decade 1880-1890 are traced and the various factors which facilitated and retarded research are examined. Alphonse Laveran's original announcement of his observation of the malaria parasite was regarded with great skepticism. This was a result of a rival claim of a bacterial cause of malarial fevers, advanced by Edwin Klebs and Corrado Tommasi-Crudeli, and because of the failure of Laveran's germ to explain the clinical diversity and pathophysiology of malaria. Changes in research technology, particularly the effective use of aniline dye stains, made possible greater precision in the study of the blood of malaria patients and in the subsequent understanding of the asexual phase of the plasmodium life cycle by Ettore Marchiafava and Angelo Celli. Until 1886, however, the study of the plasmodium was confined to a small group of researchers whose work was regarded with considerable reserve by the medical profession. Early in 1886, when Camillo Golgi coordinated the life cycle of the organism with the clinical course of the different types of malarial fever, clinicians became interested in the work. By 1890 Laveran's germ was generally accepted but most of Laveran's initial ideas had been discarded in favor of the taxonomic work and clinical pathology of the Italian school. PMID- 2578753 TI - Cerebrospinal fluid concentration of 5-hydroxyindoleactic acid in pregnancy. PMID- 2578752 TI - Comparison of histamine release in human skin mast cells induced by morphine, fentanyl, and oxymorphone. AB - Human leukocyte and skin mast cell preparations were incubated with morphine sulfate in concentrations ranging from 1.5 X 10(-5) M to 4.5 X 10(-3) M. Skin mast cells also were incubated with oxymorphone and fentanyl in the same concentrations. Human leukocytes did not release histamine in response to any concentration of morphine. In skin mast cells, histamine release by morphine first was detected at 1.5 X 10(-4) M. Histamine release further increased at 5.0 X 10(-4) M with no incremental increase at higher concentrations. Oxymorphone and fentanyl failed to release histamine at any concentration. Histamine release by morphine required calcium but was not influenced by changes in the 1-4 mM range. Skin mast cell preparations were pretreated for 30 min in naloxone 5 X 10(-4) M and then morphine 5 X 10(-4) M was added for 30 min without removing naloxone. Naloxone neither released histamine nor inhibited morphine-induced histamine release. The release of histamine by morphine but not equimolar concentrations of fentanyl and oxymorphone indicates that histamine release by narcotics is not a nonspecific effect of high drug concentration. The failure of naloxone to inhibit morphine-induced histamine release suggests that histamine release by morphine is not dependent on opiate receptor binding or activation. These results indicate that this human mast cell preparation will be useful in further understanding the mechanism of histamine release induced by morphine and other agents. PMID- 2578755 TI - Gram stain for streptococcal pharyngitis. PMID- 2578754 TI - Metabisulfite sensitivity: case report and literature review. AB - Sulfiting agents have recently been identified as food and drug additives responsible for adverse reactions. These reactions are not rare and may result in life-threatening asthma and anaphylaxis. We report a 34-year-old female with intractable asthma and urticaria. Sensitivity to sulfites was suspected based on exacerbation after restaurant meals and metaproterenol 5% inhalant solution. Bronchial provocation challenge resulted in a 28% decrease in FEV1 and a 34% decrease in FEF25-75 at the 0.01 mg/ml dose. Thirty-two cases of sulfite sensitivity reported in the literature are reviewed. Foods and drugs containing sulfites are listed. The pathogenic mechanism is unknown. The FDA allows the addition of sulfites to foods and drugs without disclosure. Only recently has this potential hazard been recognized. The FDA is considering a labeling requirement on drugs that do contain sulfites. PMID- 2578756 TI - Diagnosis of Corynebacterium pseudotuberculosis infections in sheep, using an enzyme-linked immunosorbent assay. AB - Lambs infected with Corynebacterium pseudotuberculosis (ovis) by injecting suspensions of live bacteria into the wool-free area of the axilla developed antibody against cell wall antigens and antitoxin, as measured by the enzyme linked immunosorbent assay. The toxin was a better antigen for measuring infection than was the cell wall antigen. The enzyme-linked immunosorbent assay appeared to be as sensitive as the antihemolysin inhibition test for detecting antitoxin and was easier to perform. PMID- 2578757 TI - Serum antiprotease concentrations in dogs with spontaneous and experimentally induced acute pancreatitis. AB - A significant decline (P = 0.047) in serum antiprotease concentration was detected in dogs with experimentally induced acute pancreatitis. Decreased serum antiprotease concentrations, similar in magnitude to those documented in the experimental dogs, were present in dogs with spontaneous, acute pancreatitis. These findings suggest that significant amounts of proteolytic enzymes escape into the systemic circulation during acute pancreatitis in dogs. These circulating enzymes may be involved in the extrapancreatic complications of acute pancreatitis. PMID- 2578758 TI - Quantitation of uveoscleral outflow in normotensive and glaucomatous Beagles by 3H-labeled dextran. AB - In uveoscleral outflow, aqueous humor leaves the anterior chamber and passes caudally through the trabecular meshwork and the sclerociliary cleft to enter the supraciliary and suprachoroidal spaces. The fluid is then absorbed by choroidal and scleral circulations. Using 3H-labeled dextran, uveoscleral outflow was quantitated in normotensive and glaucomatous Beagles under general anesthesia. The intrascleral plexus was isolated and 3H-labeled dextran was injected into the anterior chamber. Intrascleral plexus contents were sampled every 5 minutes over a 30- to 60-minute period. The eyes were enucleated, sectioned, and prepared for scintillation counting. Uveoscleral outflow accounted for 15% and 3% of the total aqueous humor outflow in the normotensive dogs and in the advanced glaucomatous dogs, respectively. In the advanced glaucomatous Beagle, conventional and uveoscleral outflow pathways were reduced and contributed to the etiopathogenesis of glaucoma. PMID- 2578759 TI - Morphologic studies of uveoscleral outflow in normotensive and glaucomatous beagles with fluorescein-labeled dextran. AB - Aqueous humor leaves the anterior chamber through 2 pathways: the trabecular meshwork of the iridocorneal angle and the unconventional uveoscleral route. In the latter route, aqueous humor leaves the anterior chamber, passes caudally through the trabecular meshwork and sclerociliary cleft to enter the supraciliary and suprachoroidal spaces. The fluid is absorbed by the choroidal and scleral circulation. Fluorescein-labeled dextran was slowly infused into the posterior chamber of healthy and glaucomatous Beagles for 30 minutes. The eyes were fixed in a mixture of 70% alcohol and formalin, placed in epoxy resin for histologic evaluation, and examined by fluorescent microscopy. Fluorescence was detected in the healthy dogs throughout the uveoscleral pathway. In the glaucomatous dogs, the uveoscleral outflow was decreased or completely absent. PMID- 2578760 TI - Human lung macrophages induce histamine release from basophils and mast cells. AB - Human lung macrophages isolated from surgical specimens, when cultured for 24 h, acquired the capacity to induce histamine release from human basophils. This releasing activity was entirely accounted for by soluble, nondialyzable factor(s) (molecular weight, more than 2,000 daltons) released from cultured macrophages. The basophil release reaction was dose-dependent, and also Ca++ (optimal concentration = 5 mM) and temperature (optimal = 37 degrees C) dependent. Supernatants derived from the equivalent of 3 X 10(6) macrophages/ml released 50% histamine from basophils of sensitive donors. The supernatants also induced histamine release from lung mast cells. These results are the first report of a human macrophage-derived product that activates basophils and mast cells to release histamine. PMID- 2578762 TI - Fungal stains in the acquired immunodeficiency syndrome. PMID- 2578761 TI - Smooth muscle contraction and release of histamine and slow-reacting substance of anaphylaxis in pulmonary tissues isolated from guinea pigs passively sensitized with IgG1 or IgE antibodies. AB - In previous studies, we have provided evidence that different Fc receptors mediate antigen-induced pulmonary smooth muscle contractile responses after passive sensitization of guinea pigs with IgG1 or IgE antibodies. In this study, we examined the relationship between contraction and release of histamine and slow-reacting substance of anaphylaxis (leukotrienes) in superfused trachea and parenchymal strips as well as mediator release from minced lung fragments after passive sensitization of guinea pigs with IgG1 or IgE antibodies. Guinea pigs were immunized to produce either IgG1 or IgG1 and IgE using oxazolone-guinea-pig albumin or oxazolone-Ascaris plus cyclophosphamide, respectively. The contaminating IgG1 in the IgE-rich serum was removed by passage over a protein A Sepharose column. Normal guinea pigs were passively sensitized intraperitoneally or intravenously with injections of either IgG1 or IgE 1 or 2 days before in vitro studies. Superfused tissues were challenged with 10(-1) mg/ml antigen (oxazolone-human serum albumin conjugate), and contractions and histamine and leukotriene release were monitored at discrete time intervals thereafter. At equivalent levels of contraction, substantially more histamine and leukotrienes were released from tissues taken from IgG1-sensitized animals. The amounts of histamine released from lung parenchymal strips and trachea in the IgE-sensitized state were approximately 5 and 38%, respectively, of those released from corresponding tissues in the IgG1-sensitized state. The leukotriene release from tissues isolated from IgE-sensitized animals was less than 4% of that released from tissues in the IgG1-sensitized state. Similar differences in mediator release were seen in comparable studies on minced lung fragments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578763 TI - [Significance of transitory neuromotor abnormalities. Correlation with difficulties in school-age years]. PMID- 2578764 TI - The effects of abnormal hemoglobins on a new microcolumn method to determine hemoglobin A1c. AB - A new cation-exchange microcolumn employing a borate buffer reportedly separates hemoglobin A1c from other labile glycosylated intermediates in a one step procedure. The effect of commonly occurring abnormal hemoglobins on the hemoglobin A1c (Hb A1c) levels as determined by this new technique has been studied and compared to the values obtained by isoelectric focusing. If a patient has hemoglobin levels in the normal range, or if HbS, HbE, or an elevated HbA2 are present, then hemoglobin A1c levels as estimated by this new column are unaffected or decreased. However, if HbF is elevated, a marked increase in the HbA1c level is observed. The increase is almost directly proportional to the HbF level up to 40 percent. This new column technique is therefore useful in eliminating labile glycosylated hemoglobin intermediates but must be coupled with other techniques if high HbF values are present. PMID- 2578765 TI - The formation of chlorobenzene and benzene by the reductive metabolism of lindane in rat liver microsomes. AB - The major metabolite produced by incubating [14C]lindane with rat liver microsomes under anaerobic conditions was determined to be chlorobenzene, with lesser amounts of benzene also being formed. Using relatively high lindane concentrations (250 microM), four nonvolatile metabolites of lindane were also produced anaerobically, the predominant one being identified by mass spectrometry as tetrachlorocyclohexene (TCCH). TCCH, likewise, was reduced to chlorobenzene and benzene in microsomes under anaerobic conditions. Binding of [14C]lindane to microsomal protein occurred under aerobic as well as anaerobic incubation conditions; however, lindane protein binding was greatest in anaerobic incubations compared to those containing an atmosphere of air or 100% oxygen. Hemin reduced by dithionite also readily produced chlorobenzene and benzene from lindane. These results indicate that lindane interacts readily with heme and heme proteins, including cytochrome P-450, in the absence of oxygen to undergo multiple chloride eliminations forming chlorobenzene and benzene as end products. PMID- 2578766 TI - Endocytosis of bovine lactoperoxidase by two carbohydrate-specific receptors in rat liver. AB - A perfused rat liver took up bovine lactoperoxidase (LPO) by a Ca2+-dependent, saturable process. This endocytosis was accomplished by both hepatocytes and Kupffer or other nonparenchymal cells (NPCs). The mediating receptors were the Gal/GalNAc lectin of hepatocytes and the Man/GlcNAc lectin of NPCs. Blocking either one of these receptors caused a large shift in distribution of accumulated LPO into the cell type whose receptor was left unblocked, but the extent of uptake was unaffected and the rate was only moderately reduced. Effective inhibition of overall uptake into the perfused organ required the presence of competitors for both receptors. Conversely, LPO was an effective competitor of other ligands (asialoorosomucoid or mannan) for either of the two receptors. The major clearance capacity for LPO was associated with hepatocytes which in suspension took it up by a process completely inhibitable by asialofetuin (ASF) and at a rate more than three times greater than for ASF. A faster cycling time for Gal/GalNAc receptors when bound to LPO is suggested. The glycoprotein selectively lost its affinity for Man/GlcNAc receptors when digested by endoglycosidase H (endo H), suggesting that LPO contains mannose-rich oligosaccharides. PMID- 2578767 TI - Induction of methotrexate release from rat hepatocytes in suspension by alpha adrenergic agents: involvement of calcium and metabolic energy. AB - Hepatocytes in suspension which have accumulated [3H]methotrexate release the antifolate compound into the medium upon exposure to alpha-adrenergic agents. In the presence of metabolic poisons, such as sodium azide, dinitrophenol, or dicumarol, the release of methotrexate is attenuated, indicating that integrity of the cellular metabolic apparatus is required for response to the hormonal stimulus. In the presence of millimolar concentrations of the organic acid, probenecid, release of cellular methotrexate may be reduced (1 mM probenecid) or eliminated (2 mM probenecid), suggesting the involvement of a "membrane carrier." Microtubule poisons such as vincristine, vinblastine, and griseofulvin do not modify epinephrine + isobutyl methyl xanthine (IBMX)-induced release of methotrexate. The involvement of calcium in release of methotrexate from the hepatocyte is substantiated by a dose-dependent response to the calcium ionophore, A23187, in the presence of calcium, with a lack of response in the absence of calcium. These effects of A23187 are not related to inhibition of methotrexate influx. Other putative "calcium antagonists" such as tetracaine, neomycin sulfate, and 3,4,5-trimethoxybenzoic acid [8-(diethylamino)octyl ester], do not interfere with epinephrine + IBMX-induced release of [3H]methotrexate, suggesting that these agents may not be effective probes of calcium flux in the liver cell. PMID- 2578768 TI - Cationic dye binding by hyaluronate fragments: dependence on hyaluronate chain length. AB - Sodium hyaluronate, digested with bovine testicular hyaluronidase, yielded a mixture of oligosaccharides with identical repeating disaccharide structures and differing molecular weights. The oligosaccharides were separated into a ladder like series of bands by electrophoresis on a 10% polyacrylamide gel matrix. Coelectrophoresis of purified oligosaccharides has established that adjacent bands differ in chain length by one disaccharide unit. This procedure formed the basis for a rapid screening method in which the binding of cationic dyes by hyaluronate oligosaccharides may be assayed. As a function of chain length, the oligosaccharides showed a marked change in dye binding. Species containing less than seven repeating disaccharide units are not detected by any dye tested, even at very high sample loads. Larger oligosaccharides show an increase in dye binding. The chain length at which constant maximal dye binding is reached depends on the dye structure and solvent conditions, varying from approximately 12 to 30 disaccharide units. The hyaluronate fragments of sufficient chain length to duplicate polymer behavior should be useful models for the study of hyaluronate structure and interactions in solution. PMID- 2578769 TI - [Effects of bronchial artery infusion (B-AI) with single use of MMC after intravenous peplomycin (PEP) administration in lung cancer]. AB - Effects of BAI therapy on 86 cases of lung cancer were evaluated in three groups: single-use of MMC group after intravenous PEP administration (PEP (iv).MMC group), PEP and MMC combination use group (PEP + MMC group) and single use of MMC group. Tumor regression rate determined by chest X-ray film 2 or 3 weeks after BAI was highest in the PEP (iv).MMC group followed by the PEP + MMC and MMC group. Cavity formation was more typical in the group treated with PEP + MMC. Histopathological effects were best for the PEP + MMC group followed by those of the PEP (iv).MMC and MMC group. As for side effects, pulmonary fibrosis and necrotizing bronchitis were noted in 8% of the PEP + MMC group, but side effects in the other two groups were mild. In conclusion single use of MMC after intravenous PEP administration was found to be the best way to give BAI in these three groups. PMID- 2578770 TI - [Combined chemotherapy for head and neck cancer using cisplatin, methotrexate and continuous subcutaneous infusion of peplomycin]. AB - Twenty-one patients with advanced or recurrent squamous cell carcinoma of the head and neck were treated with cisplatin, methotrexate and continuous subcutaneous infusion of peplomycin. The overall response rate was 62% (13/21) with 19% (4/21) complete response. The median duration of partial response was 2 months, while that of complete response was 3 months. Toxic effects were acceptable with no fatalities, but nephrotoxicity (33%), leukocytopenia (24%), thrombocytopenia (29%) and severe nausea and vomiting (76%) occurred. Pulmonary toxicity due to continuous subcutaneous infusion of peplomycin (15 mg/day, 4 days) was not seen. PMID- 2578771 TI - [Preparation of chromosome staining from tissue specimens]. PMID- 2578772 TI - Denver developmental screening test and preterm infants. AB - The results of Denver developmental screening test and Griffiths mental development scales examination performed on 198 preterm children during the first three years of life and compared. Using real age the former identified children with developmental delay, but labelled up to 42% of babies as having questionable or abnormal development. Using corrected age very few children showed less than normal development, and in the first year those whose Griffiths scales results showed delay were often assessed as normal by the Denver test. In view of its less satisfactory sensitivity and selectivity it is suggested that both age lines should be drawn when using the Denver test with preterm children so that undue anxiety can be allayed while appropriate action is taken to ensure adequate follow up. PMID- 2578773 TI - Effect of neonatal periventricular haemorrhage on neurodevelopmental outcome. AB - All 56 infants born between 23 and 28 weeks' gestation admitted to this hospital in 1981 were examined for periventricular haemorrhage with cerebral ultrasonography. Haemorrhage was diagnosed in 34 (61%)-12 (22%) had germinal layer haemorrhage, 18 (32%) had intraventricular haemorrhage, and four (7%) had intracerebral haemorrhage. The two year outcome of survivors with and without periventricular haemorrhage was compared to determine the effect on neurodevelopment. Only three (16%) of 19 infants with normal scans or germinal layer haemorrhages had evidence of major disability but nine (75%) of 12 infants with intraventricular or intracerebral haemorrhage had major disability. The mental and psychomotor performance on the Bayley scales of infant development was also significantly worse in the latter group. All three survivors with intracerebral haemorrhage had major disability. The continuation of life support treatment for extremely preterm infants who are at very high risk of severe handicap is a matter of increasing concern in neonatal intensive care. Our results show that if extensive periventricular haemorrhage, in particular intracerebral haemorrhage, occurs in this gestational group, extreme pessimism is warranted. PMID- 2578774 TI - Lectin-binding pattern in extramammary Paget's disease by horseradish peroxidase (HRP)-labeling method--specific staining with Dolichos biflorus agglutinin (DBA). AB - Lectin-binding pattern in extramammary Paget's disease was studied using seven different lectins (Con A, WGA, RCA-I, PNA, SBA, DBA, and UEA-I) by means of the horseradish peroxidase (HRP)-labeling method. By light microscopy it was observed that Con A, WGA, RCA-I, and DBA stained almost all the extramammary Paget cells, while PNA, SBA, and UEA-I stained only some of them. Normal keratinocytes and tumor cells from other diseases such as mammary Paget's disease, malignant melanoma, squamous cell carcinoma, basal cell epithelioma, Bowen's disease, and seborrheic keratosis were positively stained with Con A, WGA, and RCA-I, but not with DBA except in some of the mammary Paget's cells. By electron microscopy it was observed that DBA stained the cell membrane and the Golgi apparatus of the extramammary Paget cells. The present results suggest that DBA is a specific lectin for glycoconjugates in extramammary Paget cells. PMID- 2578775 TI - Relationship between the hair growth cycle and the intensity of lymphocyte induced angiogenesis in mouse skin. PMID- 2578777 TI - Shoulder-hand syndrome in patients with ovarian carcinoma. PMID- 2578776 TI - Salivary secretion and connective tissue disease in man. AB - Parotid and submandibular gland secretions collected from patients with rheumatoid arthritis or systemic sclerosis have been analysed and the results compared with those obtained from a matched group of healthy individuals. Flow rates were measured and the saliva samples assayed for amylase, kallikrein, protein, and salivary IgA concentration. The results showed that only patients with rheumatoid arthritis had a reduced salivary flow, especially parotid flow, with a significantly increased concentration of salivary IgA in both parotid and submandibular saliva. Patients with systemic sclerosis did not show significantly altered salivary flow rates, but there was a marked depletion of salivary IgA content in both parotid and submandibular saliva. Neither disease states appeared to alter the kallikrein or amylase content of saliva. The possible clinical value of these findings is discussed. PMID- 2578778 TI - Surgical palliation of respiratory insufficiency secondary to massive exuberant polyostotic fibrous dysplasia of the ribs. AB - A middle-aged man with long-standing polyostotic fibrous dysplasia had severe progressive restrictive lung disease with hypoxemia and pulmonary hypertension with heart failure because of exuberant intrathoracic, extraosseous proliferation of dysplastic tissue. Subtotal resection of this benign tissue mass ameliorated the respiratory insufficiency and led to sustained improvement in exercise tolerance, increase in pulmonary reserve, and decrease in signs of heart failure and pulmonary hypertension. PMID- 2578779 TI - Congenital polycystic tumor of the atrioventricular node. Autopsy study with immunohistochemical findings suggesting endodermal derivation. AB - Atrioventricular node congenital polycystic tumor, a lesion that causes heart block and sudden unexpected death, has been postulated to arise from the lymphatics, foregut endoderm, cardiac mesoderm, and mesothelium since its initial description in 1911. No theory concerning the histogenesis of this tumor has been completely satisfactory, either from an embryologic or a clinical standpoint. Biologic studies including cell culture systems from the lesions as well as optimal ultrastructural examination have been compromised due to postmortem autolysis. We studied four examples of this entity by standard histochemical stains for mucopolysaccharides, and by modified immunohistochemical labeling for carcinoembryonic antigen, factor VIII, and keratin. Results suggest an origin from foregut endoderm. The lesion has not been reported to be outside the region of the atrioventricular junction, but was demonstrated in the thymus gland in one of our cases. PMID- 2578780 TI - Rehabilitation of an adult with disabilities due to congenital sensory neuropathy. AB - A 37-year-old woman presented with congenital loss of all peripheral sensory modalities, sparing only her face, paraspinal area and proximal limbs. She was otherwise neurologically normal. Her sensory neuropathy was complicated by autoamputation of phalanges, pathologic fractures, failed total hip replacement, burns, pressure ulcers, and a painless peptic ulcer. An unusual cluster of functional deficits occurred when she was unable to substitute vision for peripheral sensibility. In the sudden darkness of a power failure she would fall to the floor; we advised the installation of battery-operated safety lights activated by a drop in line voltage. Voice-activated lights overcame difficulty in finding light switches in darkened rooms. She was unable to drive at night until she had a light placed under the dashboard of her car so she could see the foot pedals. She was unable to wash her hair, as shampoo irritation made her close her eyes and lose balance; swimming goggles and a nonfogging mirror permitted independence in her hair care. The solution of these functional difficulties provides a fresh perspective on the rehabilitation of patients with severe sensory impairments, especially with a cooperative family. PMID- 2578781 TI - Monoclonal antibodies directed to E1 glycoprotein of rubella virus. AB - We have prepared four monoclonal antibodies to rubella virus E1 glycoprotein. Three nonoverlapping antigenic sites were delineated on E1 protein by competitive binding assays. Antibodies binding to one site were characterized by high hemagglutination inhibition (HI) titer but poor neutralizing activity. The addition of antiglobulin conferred neutralizing activity. Antibodies directed to two other antigenic sites had modest hemolysis inhibition but little or no HI and neutralizing activities. The addition of antiglobulin markedly augmented HI activity but had little effect on neutralizing activity. Epitopes defined by three antibodies were conserved among four rubella virus strains examined. PMID- 2578783 TI - A serological classification of bovine enteroviruses. AB - Cross virus neutralization (VN), complement fixation (CF) and immunoprecipitation (IP) tests were employed to compare the seven currently recognized bovine enterovirus (BEV) serotypes with seven serologically distinct strains previously isolated in Great Britain and two other BEV from the United Kingdom. Based on criteria used to differentiate other human and animal picornavirus serotypes, it was discovered that BEV types 1, 4, 5 and 6 were related to each other and could be included in a single serotype. Types 3 and 7 were found to be identical, and related to serotype 2. All of the other nine BEV were included in either serotype 1 or 2. Not all of the strains in each serotype were identical and antigenic variants were designated as subtypes. Antigenic relationships not revealed by VN were demonstrated in CF and IP tests. Bovine enterovirus strains whose antisera had the broadest intratypic reactivity were suggested as prototypes. The two proposed BEV serotypes could also be distinguished by their ability to agglutinate erythrocytes. Guinea pig erythrocytes were agglutinates by both serotypes while sheep red cells only reacted with serotype 1. PMID- 2578782 TI - Evidence for retrovirus in miniature swine with radiation-induced leukemia or metaplasia. AB - Biochemical and morphological evidence indicates that a type-C retrovirus is present in the blood of swine (both leukemic and nonleukemic) exposed to strontium-90 radiation. Nonexposed swine that were leukemic also had virus present. The virus was shown to contain an RNase-sensitive DNA polymerase activity with cation, detergent and template requirements similar to those of known viral reverse transcriptases. The buoyant density of the virus was 1.14 to 1.16 g/ml, which can be converted, by treatment with ether, to a virion core having a density of 1.20 to 1.23 g/ml. Linear regression analysis indicated a correlation between virus-associated DNA polymerase activity and the number of blast cells in the peripheral blood. PMID- 2578784 TI - Antigenic characterization of hemagglutinin-neuraminidase (HN) protein of avian paramyxoviruses by specific antisera to isolated HN subunits. AB - Specific antisera for the isolated HN proteins of eight reference strains of avian paramyxoviruses could be prepared in guinea pigs by intraperitoneal injection of guinea pig red blood cells (GRBC) coated with purified HN proteins. In the hemagglutination inhibition (HI) tests, all reference strains reacted strongly with each homologous antiserum to the isolated HN showing that a low level of cross-reactivity among the reference strains was greatly diminished by using specific antisera. Immuno-double-diffusion (IDD) tests showed that all antisera except those to turkey/Wisconsin/68 and duck/Hong Kong/D3/75 gave single well-defined lines only with the homologous viruses. The remaining two antisera developed a single definite precipitin line together with weak lines with homologous virus. Two isolates in Japan were clearly identified in HI and IDD tests with specific antisera to the HN subunits of the reference strains suggesting that the antisera were useful for identification of avian paramyxovirus isolates. Two isolates in Japan, H-70 from a munia-bird and Y-7 from a duck were found to have HN proteins related closely to those of finch/N. Ireland/Bangor/73 and duck/Hong Kong/199/77, respectively. PMID- 2578785 TI - Monoclonal antibodies against five structural components of measles virus. II. Characterization of five cell lines persistently infected with measles virus. AB - Groups of monoclonal antibodies against measles virus nucleoprotein (NP), phosphoprotein (P), matrix (M), hemagglutinin (H) and fusion (F) components were used for characterization of 5 persistently infected cell lines. In four of these lines (Lu106 carrier, MaSSPE, MaPi, HEpPi) all cells were infected but the cells mostly produced noninfectious virus products. The fifth line (HNT in vero cells) did not produce any infectious virus and only a fraction of the cells were infected in most passages. In agreement with earlier findings the virus strains showed marked variations in the M epitope pattern and also some variation in the H epitope pattern. In addition epitope variations were found in both NP and P protein, which contrasted with conserved antigen characteristics of these components in lytically replicating virus. Restriction of fusion in the persistent infections was studied further. HNT and Lu 106 cells showed selective quantitative restriction in F protein synthesis. Lu106 cells were found to contain distinct epitopic F species. In contrast MaSSPE cells produced readily detectable cleaved F protein and in addition extracellular virus products carried hemolytic activity. The fact that no cell fusion occurred was interpreted to be due to particular properties of the Ma 106 cells, a concept supported by the absence of fusion of these cells when infected with syncytiogenic measles virus. It is concluded that (a) under conditions of persistence of measles-virus without requirement for synthesis of complete virions a more pronounced variation in epitope characteristics of virus components is encountered than in lytic infections; and b) that persistence of measles virus shows individualistic characteristics which may reflect changes in the virus and/or innate properties of the host cells. PMID- 2578786 TI - Amplification of herpes simplex virus resistance in mouse neuroblastoma (Cl300) cells. AB - Clones of mouse neuroblastoma (Cl300) cells with increased resistance to herpes simplex virus (HSV) were obtained among survivors after prolonged exposure of partially HSV resistent Cl300 cells to successively increasing multiplicities of infection (MOI) of HSV. The increased restrictedness to HSV of these Cl300 R clones (Cl300 RI and Cl300 RII) as compared to the parental Cl300 cells was demonstrated by a tolerance to higher MOIs of HSV, judged by the appearance of cytopathic effects; by lower yields of progeny virus; and by higher activities of a non-interferon HSV inhibitor. Morphological appearance, cellular growth rate as well as HSV adsorptive capacity of the Cl300 R cells did not differ from that of Cl300 cells. Neither was virus penetration affected. These neuroblastoma Cl300 R cells, demonstrating an amplified resistance to HSV, might serve useful in studies on the regulation of virus replication in HSV latency establishment in neurons. PMID- 2578788 TI - Inhibition of RNA-directed DNA polymerase from avian myeloblastosis virus by a 5 benzyl-6-aminouracil. AB - 5-(p-Chlorobenzyl)-6-aminouracil (5-ClAU) inhibited RNA-dependent DNA polymerase (reverse transcriptase) from avian myeloblastosis virus. Inhibition was expressed only in the presence of a polyribonucleotide template such as mRNA or poly(rA), and kinetic analysis suggested that the action of 5-ClAU is competitive with template:primer. 5-ClAU did not inhibit HeLa DNA polymerase gamma, an enzyme that efficiently copies polyribonucleotide templates. A mechanism is proposed in which a 5-ClAU:template complex interferes with enzyme function, based partly on NMR studies indicating that 5-ClAU can form a hydrogen-bonded complex with deoxyadenosine in solution. PMID- 2578787 TI - Binding of neutralizing monoclonal antibodies to empty capsids of poliovirus can be blocked by monospecific antisera to structural polypeptides VP1 and VP2. AB - Binding of two neutralizing monoclonal antibodies (Nt-mAbs) to natural empty capsids (NEC) of poliovirus, type 1, was blocked to the extent of 83 per cent to 98 per cent by monospecific rabbit antisera directed against the structural polypeptides VP1 and VP2. Monospecific antisera against VP3 or VP4, however, did not show this blocking effect. It is therefore assumed that VP1 and VP2 are located close together at the antigenic sites for the two mAbs. PMID- 2578789 TI - On the binding of brain myelin basic protein to chromatographic resins. AB - Myelin basic protein, only in association with certain detergents, is able to bind irreversibly to the usual gel filtration media. While this binding is greatly advantageous in purification of proteolipid (the other major myelin protein), the question arises of the uncommon, nonphysiological behaviour of the basic protein. A relationship between binding property and basic protein structure is suggested. PMID- 2578790 TI - Afrikander cattle congenital goiter: size heterogeneity in thyroglobulin mRNA. AB - The mRNA coding for thyroglobulin in cattle homozygous for an autosomal recessive defect of thyroglobulin synthesis was investigated using a recombinant plasmid containing bovine mRNA coding sequence. Total RNA preparations from goiter contained one third of the thyroglobulin mRNA sequences found in normal thyroid tissue. This mRNA was not translated into thyroglobulin by Xenopus oocytes. Northern transfer analysis revealed both a normal sized and a smaller thyroglobulin mRNA in the goiter. PMID- 2578791 TI - The structures of the serine-linked sugar chains on human chorionic gonadotropin. AB - The human chorionic gonadotropin beta-subunit tryptic COOH-terminal peptide (residues 123-145) which contains 3 serine-linked sugar chains was isolated. The sugar chains were cleaved by beta-elimination and then separated by gel filtration. The peaks were pooled and their compositions determined. The products of serial glycosidase digestion and periodate oxidation of the intact glycopeptide were also characterized. Of the serine-linked sugar chains, 13% were the hexasaccharide NeuAc alpha 2,3 Gal beta 1,3 (NeuAc alpha 2,3 Gal beta 1,4 GlcNAc beta 1,6) GalNAc, 34% the tetrasaccharide NeuAc alpha 2,3 Gal beta 1,3 (NeuAc alpha 2,6) GalNAc, 43% the trisaccharide NeuAc alpha 2,3 Gal beta 1,3 GalNAc and 10% the disaccharide NeuAc alpha 2,6 GalNAc. PMID- 2578792 TI - Isolation and characterization of rat intestinal polyribosomes and RNA during absorption of fat. Increased translation in vitro of apo-AIV. AB - Polyribosomes were isolated from the intestinal mucosa of fasted and fat-fed rats in the presence of ribonuclease inhibitors. Polyribosomes from fat-fed rats were larger and more efficient in incorporating radioactive aminoacids into proteins than those from fasted rats. Total RNA prepared by guanidine-HCl extraction, from the intestine of fasting and fat-fed rats were translated in vitro in a mRNA dependent rabbit reticulocyte lysate system in the presence of 35S-methionine. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography of the synthesized peptides showed a relative increase in the radioactivity of some peptides of RNA from fat-fed animals and particularly a two fold increase in preapo-AIV indicating that the intestinal apo-AIV synthesis is under transcriptional regulation by the metabolic processes involved in fat transport, that is, triglyceride-rich lipoprotein production. PMID- 2578793 TI - Antigenic stimulated release of arachidonic acid, lipoxygenase activity and histamine release in a cloned murine mast cell MC9. AB - A cloned murine mast cell MC9 expresses phospholipase and lipoxygenase activity when stimulated with IgE and hapten. Addition of DNP-BSA to sensitized MC9 cells causes release of 58% of the cell histamine and 127 pmoles LTC4/10(6) cells. Prelabelling studies with [1-14C]-arachidonic acid showed that LTC4 production was proceeded by the release of arachidonic acid from membrane phospholipids. Approximately 8.7% of the cell arachidonic acid was released and half of this was converted to LTC4. The remaining radioactivity was converted to diHETES including LTB4 (15%), 5-HETE (10%), free arachidonic acid (10%), reesterified 5-HETE and arachidonic acid (8%) and prostaglandins (7%). This stimulation was dependent on hapten (DNP-BSA) and extracellular Ca++. Under identical conditions the calcium ionophore A23187 stimulated the release of 10.3% of the total cell arachidonic acid, and 51% of this was metabolized to LTC4. In addition the ionophore stimulated the release of 61% of the total cellular histamine. PMID- 2578794 TI - Presynaptic heteroreceptors in regulation of neuronal transmission. PMID- 2578795 TI - Effect of ethanol on turpentine-induced acute phase response in rats. AB - Turpentine-induced acute-phase response and its modulation by ethanol in rats at 48 hr has been studied. There was more than 2.3-5.1 fold increase in fibrinogen and seromucoids concentrations in plasma, accompanied by 28% decline in albumin concentration in turpentine-stimulated rats. The fractional synthesis rate of these two acute-phase proteins was increased by 4.1-6.4 fold, while that of albumin (non acute-phase protein) was reduced by 32.6%. Ethanol inhibited this induction of acute-phase protein synthesis at 48 hr. The inhibition of acute phase response by ethanol was significantly more pronounced for seromucoids than for fibrinogen and appeared to be dependent on the carbohydrate content of the acute-phase glycoprotein. PMID- 2578796 TI - Role of electrophysiologic testing in the selection of patients requiring pacemaker implantation. PMID- 2578797 TI - [Cell biological study on ataxia-telangiectasia]. PMID- 2578799 TI - Gastric epithelial mucus--a densitometric histochemical study of aspirin-induced damage in the rat. AB - In an attempt to elucidate which mechanisms of mucus barrier breakdown are important in the formation of gastric erosions, changes occurring in the epithelial mucin content of gastric mucosa exposed to a damaging agent were studied quantitatively. Male Wistar rats (n = 30) were starved for 24 h, then dosed orally with aspirin suspension (300 mg/kg body weight). Animals were killed after 3, 5 or 9 h. Paraffin sections of gastric mucosa were prepared from each and were stained with Alcian blue pH 2.5 (for acidic glycoproteins) or PAS (neutral glycoproteins). Control animals (n = 15) were treated identically, apart from the omission of aspirin from the suspension. The mean integrated optical density (IOD) of each slide was measured using a Vickers M85 Microdensitometer. The mean IOD for PAS-stained sections dropped to 50% of the control value in the 3-h group (P less than 0.001), returning to 84% of the control value in the 5-h group and normal in the 9-h group. In contrast, mean IOD for Alcian blue stained sections was only marginally reduced after 3 h, but showed considerable reduction in the 5-h (57% of control value) and 9-h (61% of control value) groups. It is suggested that this diminished epithelial mucin content is a consequence of cellular exfoliation. Such depletion of epithelial mucin content represents a diminished source of supply for the surface gel, the reduced thickness of which would compromise the 'mucus-bicarbonate' barrier. PMID- 2578798 TI - Effects of sodium n-butyrate on alpha-fetoprotein and albumin secretion in the human hepatoma cell line PLC/PRF/5. AB - The in vitro effects of sodium n-butyrate (butyrate) on the growth, morphology and secretion of alpha-fetoprotein (AFP) and albumin by the human heptoma cell line PLC/PRF/5 were studied. Butyrate caused a marked reduction in the growth rate, colony forming efficiency in soft agar and de novo synthesis of DNA as well as remarkable morphological changes including cell enlargement, flattening and a decreased number of nucleoli. Secretion of AFP was reduced during culture with butyrate, while that of albumin was increased. The requirement of de novo protein synthesis for the increase in albumin and decrease of AFP by butyrate was demonstrated by inhibition studies with cycloheximide. These results suggest that butyrate caused the hepatoma cells to acquire in vitro properties that are considered to be more consistent with normal liver cells. PMID- 2578800 TI - Alpha 1-microglobulin: a new antigenic component of the epidermo-dermal junction in normal human skin. AB - Monoclonal antibodies to human alpha 1-microglobulin (alpha 1-m), a glycoprotein present in most biological fluids, reacted with the basement membrane of the epidermo-dermal junction and that of eccrine sweat glands in normal human skin. This immunofluorescence was specific in that control antibodies of known well defined reactivity did not stain these structures. Therefore, alpha 1-m seems to be a new antigenic component of the junction and it may be an interesting antigen to study in diseases of this area. PMID- 2578801 TI - Paget cells express cytokeratins typical of glandular epithelia. AB - The expression of cytokeratins in Paget cells in mammary and extramammary Paget's disease was studied using different keratin antibodies and immunofluorescence microscopy. Antibodies to epidermal keratin did not react with the Paget cells but stained the surrounding epidermis. Two monoclonal cytokeratin antibodies (PKKI and RGE 53), which reacted typically with simple glandular epithelia in normal tissues, brightly stained the Paget cells and left the surrounding epidermal cells unstained. The results indicate that Paget cells are derived from mammary or sweat duct epithelium rather than from epidermal cells. PMID- 2578802 TI - Stability of azure B-eosin Y staining solutions. AB - The stability of azure B-eosin Y staining solutions of varying composition and of a routine May Grunwald Giemsa (MGG) stain were studied by analysis of the density histogram of white blood cells obtained by an image analysis computer. The stability appeared to be variable and depended on the concentration of the dyes, the molarity of the buffer solutions and the presence of dimethylsulfoxide (DMSO) as a stabilizer. Although most staining solutions including the routine MGG stain showed marked loss of staining capacity soon after preparation, it was possible to obtain an azure B-eosin Y mixture with very satisfactory staining properties which did not decrease during 8 h after its preparation. PMID- 2578803 TI - Five haplotypes in Black beta-thalassaemia heterozygotes: three are associated with high and two with low G gamma values in fetal haemoglobin. AB - Genotypes at seven different polymorphic restriction sites (5' to the epsilon gene, at the G gamma, at the A gamma, at the psi beta, 3' to the psi beta, at the beta, and 3' to the beta genes) were analysed by restriction endonuclease mapping of the DNA from 66 Black beta-thalassaemia heterozygotes from Georgia and several of their normal relatives. Five different haplotypes were observed. Three of these were associated with high G gamma values in the small amount of Hb F (0.8 8.3%) present in the blood of these patients and two with low G gamma values. One haplotype [- + - + + + +] that occurred on two of every three beta thalassaemia chromosomes was associated with high G gamma levels, and is the same as that found in some Black SS patients also having high G gamma values (Gilman & Huisman, 1984). Two others [- + + - + - +] and [- + - - + + +] were also associated with high G gamma, while two [- - - - + + +] and [+ - - - - + +] were associated with low G gamma. Variation in haematological data, mainly MCV and MCH values, was found to be caused in part by the type of beta-thalassaemia (defined by its haplotype) and by the presence of an additional alpha-thalassaemia-2 heterozygosity or homozygosity. PMID- 2578804 TI - (A gamma delta beta)0-Thalassaemia in Blacks is due to a deletion of 34 kbp of DNA. AB - DNA from members of 10 Black families with conditions considered to be G gamma (delta beta)0-thalassaemia or G gamma (delta beta)0-HPFH were studied by using restriction enzyme analysis. One or more affected members from each family were shown to have the same deletion of 34 kbp of DNA in the human beta-globin gene cluster. A clone spanning the deletion was isolated from the DNA of one such person and studied in detail. The deletion removed part of the A gamma and all of the psi beta, delta and beta-globin genes and is different from the four previously identified deletions which caused a condition presently known as (A gamma delta beta)0-thalassaemia. PMID- 2578805 TI - The sequence of the A gamma globin gene in a G gamma beta+ type of hereditary persistence of fetal haemoglobin. AB - The sequence of the A gamma globin gene from the affected chromosome of an individual heterozygous for the G gamma beta+ type of hereditary persistence of fetal haemoglobin (G gamma beta+ HPFH) is reported. With two exceptions, it is identical to one of the two allelic A gamma globin genes already sequenced and there is therefore no change which could explain the absence of its expression in the face of the persistent G gamma globin expression which is a feature of this condition. PMID- 2578806 TI - The haematology of steady state homozygous sickle cell disease: frequency distributions, variation with age and sex, longitudinal observations. AB - The steady state haematological characteristics observed in 1071 patients with homozygous sickle cell (SS) disease aged 5-66 years are presented. Cross sectional studies indicated that HbA2 levels were consistently higher in males but no age related change was apparent. Fetal haemoglobin levels were consistently higher in females and fell significantly in males between the 5-9 and 10-14 year age groups. Total haemoglobin was significantly higher in females before age 15 and higher in males after 20 years, a dramatic age related rise occurring in males between the 10-14 and 25-29 year age groups, and a fall in patients aged 40 years and over. The mean cell volume was consistently greater in females after 15 years and a marked age related rise occurred in both sexes between the 5-9 and 25-29 year age groups. Counts of irreversibly sickled cells were consistently higher in males. Reticulocytes fell significantly with age, while platelets and total bilirubin fell significantly after the age of 15 years. Longitudinal studies confirmed the increase in total haemoglobin levels in males over the ages 10-14 years, and a significant fall in males after the age of 30 years. Such studies also confirmed the fall in HbF in males aged 5-14 years, the increase in MCV in both sexes aged 5-29 years, and the fall in platelet counts in both sexes over the age of 20 years. These observations provide 'normal' values for patients seen elsewhere and also contribute to an understanding of factors determining the haemoglobin indices in SS disease. PMID- 2578807 TI - Phylogenetically more conservative epitopes among monoclonal antibody-defined antigenic sites of human transferrin are involved in receptor binding. AB - Of eight monoclonal antibodies raised against human transferrin, one (H.TF-14) cross reacted with pig and rabbit transferrins and one (H.TF-1) showed cross reactivity with horse and dog transferrins. While rabbit and pig transferrins exhibited the same patterns of binding to MOLT-3 cell receptors as human and horse transferrins, binding of mouse and dog transferrins was weaker and bovine and carp transferrins gave entirely negative results. The results of these competitive binding experiments were confirmed by a biological test in which bovine transferrin had no effect on the growth of MOLT-3 cells when added to a serum-free medium. The observed correlation between cross-reactivity of anti transferrin monoclonal antibodies and the binding abilities of transferrins to the MOLT-3 cell receptors may be associated with the conservatism of the part of the transferrin molecule recognized by the cell receptor. PMID- 2578808 TI - Unmasking of Kx antigen by reduction of disulphide bonds on normal and McLeod red cells. AB - We have investigated the effect of dithiothreitol (DTT) treatment of human red cells upon the Kx blood group antigen. At low concentrations of DTT (less than or equal to 2 microM) there is enhancement of the Kx antigen concomitant with the complete denaturation of the Jsa and Jsb antigens of the Kell blood system. This unmasking of the Kx antigenic site is near maximal using 2 microM DTT. At this concentration of DTT, only the Jsa and Jsb antigens are completely denatured; all other Kell system antigens tested (K, k, Kpb, Ku) are essentially unaffected. These results argue against the Kx antigen serving strictly as a carbohydrate precursor substance involved in a sequential biosynthetic pathway of Kell blood group antigens. Also, McLeod red cells, after treatment with DTT, were found to contain Kx antigen, although in much lower density than normal red cells, indicating that, although not a typical carbohydrate precursor substance, Kx may, nevertheless, be essential for the serological expression of Kell related antigens. It is hypothesized that the Kx structure and the Kell blood group antigen structure are two separate subunits associated in a quaternary conformation involving at least one interchain S-S bond. Our results should allow for a clearer understanding of the relationship between the serological expression of the Kx antigen and the serologically observed reactivity of the Kell blood group antigens of individuals having normal, Ko and McLeod phenotypes. PMID- 2578809 TI - Factors affecting the transport of beta-amino acids in rat renal brush-border membrane vesicles. The role of external chloride. AB - The effect of a variety of ions and other solutes on the accumulation of the beta amino acid, taurine, was examined in rat renal brush-border membrane vesicles. Initial taurine uptake (15 and 30 s) is sodium-dependent with a typical overshoot. This Na+ effect was confirmed by exchange diffusion and gramicidin inhibition of taurine uptake. External K+ or Li+ do not increase taurine accumulation more than Na+-free mannitol, except that the combination of external K+ and Na+ in the presence of nigericin enhances uptake. Of all anions tested, including more permeant (SCN- and NO3-) or less permeant (SO4(2-)), chloride supported taurine accumulation to a significantly greater degree. Preloading vesicles with choline chloride reduced taurine uptake, suggesting that external Cl- stimulates uptake. Since this choline effect could be related to volume change, due to the slow diffusion of choline into vesicles, brush-border membrane vesicles were pre-incubated with LiCl, LiNO3 and LiSO4. Internal LiCl, regardless of the final Na+ anion mixture, reduced initial rate (15 and 60 s) and peak (360 s) taurine uptake. Internal LiNO3 or LiSO4 with external NaCl resulted in similar or higher values of uptake at 15, 60 and 360 s, indicating a role for external Cl in taurine uptake in addition to Na+ effect. Although uptake by vesicles is greatest at pH 8.0 and inhibited at acidic pH values (pH less than 7.0), an externally directed H+ gradient does not influence uptake. Similarly, amiloride, an inhibitor of the Na+/H+ antiporter, had no influence on taurine accumulation over a wide variety of concentrations or at low Na+ concentrations. Taurine uptake is blocked only by other beta-amino acids and in a competitive fashion. D Glucose and p-aminohippurate at high concentrations (greater than 10(-3) M) reduce taurine uptake, possibly by competing for sodium ions, although gramicidin added in the presence of D-glucose inhibits taurine uptake even further. These studies more clearly define the nature of the renal beta-amino acid transport system in brush-border vesicles and indicate a role for external Cl- in this uptake system. PMID- 2578810 TI - Isolation of cellular membranes from rat mast cells. AB - Large amounts of membranes enriched either in perigranular membranes or in plasma membranes have been successfully isolated from rat peritoneal mast cells. A cycle consisting of a single sonication pulse to disrupt the mast cells followed by centrifugation to separate the released granules was repeated until 90% of the mast cells were disrupted. This technique resulted in a high yield of intact granules since the released granules were only exposed to the single sonication pulse. The intact granules were separated from plasma membrane fragments by centrifugation through a Percoll gradient. The perigranular membranes were then obtained by osmotic lysis of the purified intact granules. The plasma membrane fraction was enriched 4.5-fold (range, 4.1-6.1) in 5'-nucleotidase activity, a plasma membrane marker enzyme. No suitable marker enzyme activity was found for the perigranular membrane fraction. An important aspect of this procedure is its potential for obtaining both a plasma and perigranular membrane preparation in high yield and purity from the same mast cell preparation. PMID- 2578811 TI - Interactions of hexachlorocyclohexanes with the (Ca2+ + Mg2+)-ATPase from sarcoplasmic reticulum. AB - Hexachlorocyclohexanes have been shown to inhibit the (Ca2+ + Mg2+)-ATPase of muscle sarcoplasmic reticulum reconstituted into bilayers of dioleoylphosphatidylcholine. However, for the ATPase reconstituted into bilayers of dimyristoleoylphosphatidylcholine, a pattern of activation at low concentration followed by inhibition at higher concentration is seen for hexachlorocyclohexanes and alkanes such as decane and hexadecane. The ATPase in sarcoplasmic reticulum vesicles is also inhibited by the hexachlorocyclohexanes. The effects of hexachlorocyclohexanes on activity are largely independent of concentrations of Ca2+ and ATP. Inhibition is more marked at lower temperatures. The hexachlorocyclohexanes quench the tryptophan fluorescence of the ATPase, and the quenching can be used to obtain partition coefficients into the membrane system. As for simple lipid bilayers, partition exhibits a negative temperature coefficient. Binding is related to effects on ATPase activity. PMID- 2578812 TI - Determining the kinetics of membrane pores from patch clamp data without measuring the open and closed times. AB - We present a new and very time saving way to determine kinetic rate constants from patch clamp data by using the correlation functions utilized in analyzing experiments with photon correlations. PMID- 2578813 TI - The 35 kDa DCCD-binding protein from pig heart mitochondria is the mitochondrial porin. AB - The protein which can be labelled by low concentrations of dicyclohexylcarbodiimide in the Mr region of 30 000-35 000 has been purified from pig heart mitochondria with a high yield and as a single band of apparent Mr 35 000 in dodecyl sulphate-containing gels. The protein is not identical with the phosphate carrier as suggested before, since the two proteins behave differently during isolation. Incorporation of the isolated 35 kDa dicyclohexylcarbodiimide binding protein into lipid bilayer membranes causes an increase of the membrane conductance in definite steps, due to the formation of pores. The specific pore forming activity increases during the purification procedure. The single pore conductance is about 4.0 nS, suggesting a diameter of 1.7 nm of the open pore. The pore conductance is dependent on the voltage across the membrane. Anion permeability of the pore is higher than cation permeability. These properties are similar to those described for isolated mitochondrial and bacterial porins. It is concluded that the 35 kDa dicyclohexylcarbodiimide-binding protein from pig heart mitochondria is identical with porin from outer mitochondrial membrane. PMID- 2578814 TI - Rapid reconstitution and characterization of highly-efficient sarcoplasmic reticulum Ca pump. AB - The Ca pump was reconstituted from the purified sarcoplasmic reticulum ATPase and excess soybean phospholipids by the freeze-thaw sonication procedure in the presence of cholate. In the absence of Ca precipitating agents, the reconstituted proteoliposomes accumulated Ca2+ at an initial rate of up to 0.7 mumol/mg per min at 25 degrees C, and a value of 1.54 was obtained for the coupling ratio between Ca uptake and Ca2+-dependent ATPase activities. The proteoliposomes were mainly unilamellar vesicles but were heterogeneous with respect to their size. When reconstituted at a lipid/protein ratio of 40, proteoliposomes had a buoyant density of about 1.04 and their average internal volume was 1.4-1.6 microliters/mg of phospholipids. More than 95% of the ATPase was incorporated randomly into these proteoliposomes and the fraction of proteoliposomes that represented about 50% of the total intravesicular isotope space contained right side-out oriented enzyme. 86Rb efflux from the 86Rb-loaded proteoliposomes was found to be slow even at 25 degrees C. Therefore, the proteoliposomes prepared by the present simple method should be useful for the study of the side-specific interaction of ions such as alkali metal cations with the sarcoplasmic reticulum Ca pump. PMID- 2578815 TI - Long interspersed sequences in mammalian DNA. Properties of newly identified specimens. AB - The genomes of primates and of rodents contain numerous long interspersed sequences or LINEs, which are mutually homologous and show characteristics of inserted reverse transcripts or retroposons. Here I report the identification of five new specimens in published DNA sequences, including the first two examples from the rat. These specimens demonstrate the generality of certain sequence arrangements seen in LINEs, viz.: 5' truncation; internal inversion with deletion; clustering with other retroposons; and evolutionary divergence at the 3' end. The 3' segments show a patchwork pattern of homology suggestive of frequent sequence exchanges between multiple subfamilies. PMID- 2578816 TI - Verification of a new model of the time course of RNA synthesis. Measurement of the rates of initiation and elongation. AB - The time course of RNA synthesis in vitro commonly starts with a lag followed by a linear phase. Differing from the earlier interpretation we have previously proposed that, under conditions where the initiation rate is low, the lag represents the time taken for the first RNA polymerase molecule to reach a termination site. During the linear phase, initiation is balanced by termination (Mahon, G.A.T., McWilliam, P., Gordon, R.L. and McConnell, D.J. (1980) J. Theor. Biol. 87, 483-515). We report the use of rifampicin as a further test of this new model. We show that it does apply under conditions of high ionic strength (0.3 M KCl), and under these conditions time courses may be analyzed to yield unbiased estimates of the initiation (Vi) and chain elongation (Vp) rates. We illustrate the application of the method of time course analysis and confirm some of its features by examining the effect of variation in the concentrations of RNA polymerase and nucleoside triphosphate on the estimates of Vi and Vp. The alternative interpretation of the time course applies under conditions of low ionic strength, where the initiation rate is high. (Chamberlin, M.J., Nierman, W.C., Wiggs, J. and Neff, N. (1979) J. Biol. Chem. 254, 10061-10069.) The advantages of each model in measuring Vi and Vp (the major parameters of the transcription reaction) are discussed. PMID- 2578817 TI - Biosynthesis and cytoplasmic distribution of small poly(A)-containing B2 RNA. AB - Previously, we described a small polyadenylated RNA predominantly located in cytoplasm and hybridizing with the ubiquitous B2 sequence of the mouse genome (Kramerov, D.A., Lekakh, I.V., Samarina, O.P. and Ryskov, A.P. (1982) Nucleic Acids Res. 10, 7477-7491). This 180-300 nucleotide long RNA was designated B2 RNA. Here, we demonstrate that B2 RNA is complementary to just one of the strands of cloned B2 sequence. The synthesis of B2 is rather resistant to ultraviolet irradiation of Ehrlich ascites carcinoma cells. The treatment of the cells with alpha-amanitin at a concentration completely blocking the formation of small nuclear RNAs U1, U2 and U3 does not interfere with the B2 RNA synthesis. These results suggest that B2 RNA formation is directly transcribed with the aid of RNA polymerase III, rather than being formed in the course of the processing of large RNA molecules which are known to contain a lot of B2 sequences. We also surprisingly found that the synthesis of up to 50% of long poly(A) +RNA in Ehrlich carcinoma cells is rather resistant to alpha-amanitin. The possible role of genetic elements including B2 sequences able to promote large RNA-polymerase III transcripts is discussed. B2 RNA in the cytoplasm is incorporated into the ribonucleoprotein particles, both small (12-18 S) and heavy. The latter probably correspond to informosomes. After deproteinization of heavy particles, a major part of B2 RNA still cosediments with mRNA and is split from it only after denaturation. We suggest that the B2 RNA of heavy ribonucleoproteins is associated with mRNA by short complementary stretches. About half of the B2 RNA is recovered in the cytoskeletal fraction. The possible role of B2 RNA in mRNA transport or in translation regulation is discussed. PMID- 2578818 TI - Isolation and characterisation of keratin mRNA from the scale epidermis of the embryonic chick. AB - The keratin polypeptides of the epidermis from the leg scale region of 17-day-old embryonic chicks were extracted as S-carboxymethylated derivatives and characterised by electrophoresis on SDS and pH 9.5 urea gels including a combination of both in two dimensions. Proteins were isolated that gave X-ray diffraction patterns typical of alpha- and beta- (avian feather) keratins. An mRNA fraction was isolated from 17-day-old scale tissue by guanidinium chloride extraction and sucrose gradient fractionation. The mRNA was translated in the wheat germ system to give a major product indistinguishable from the molecular weight class (Mr 14 500) of scale beta-keratin polypeptides. A cDNA library was constructed in pBR322 from a 15 S mRNA subfraction and two recombinant clones were selected by their strong hybridisation to cDNA prepared from the 15 S mRNA. The sequencing of these has yielded details of the relatedness of two scale keratin genes including their 3' untranslated regions. Almost half of the protein sequences of the two homologous scale keratins has been deduced and a notable feature of the scale keratin structure appears to be the presence of at least two sequence domains consisting of 13 amino acid repeats. PMID- 2578819 TI - 2'-Fluoro-2'-deoxycytidine triphosphate as a substrate for RNA- and DNA-dependent DNA polymerases. AB - The ability of the analog 2'-fluoro-2'-deoxycytidine triphosphate (dCflTP) to be used as a substrate in the reactions catalyzed by Xenopus laevis oocytes DNA polymerase alpha and AMV reverse transcriptase has been studied. The apparent Km values for dCTP and dCflTP, using activated DNA as templates, were 0.6 microM and 7 mM with DNA polymerase alpha and 0.14 microM and 7 microM with AMV reverse transcriptase, respectively. As observed with dCTP, aphidicolin was a noncompetitive inhibitor in the DNA polymerase alpha-catalyzed DNA synthesis; the Ki values were about 2 microM for both substrates. dCflTP can also be incorporated into DNA synthetized by other eukaryotic DNA polymerases and by reverse transcriptase with RNA as a template, both in the presence or absence of (dT)12 primer. PMID- 2578821 TI - Differential post-translational modification of human type I keratins synthesized in a rabbit reticulocyte cell-free system. AB - The translation products synthesized in a rabbit reticulocyte lysate system, from total cellular mRNA from the human epithelial cell-line ME-180, have been examined. Keratin proteins are prominent among these translation products, and they precisely coelectrophorese in sodium dodecyl sulfate-polyacrylamide gels with keratins purified from the cells. Type-I, acidic, keratins which are acetylated in vivo, are also acetylated by the reticulocyte lysate. Examination by two-dimensional electrophoresis, of two acidic keratins known to be phosphorylated in vivo reveals that only one of these proteins is phosphorylated in the lysate system. Phosphorylation of this protein occurs after release of the completed polypeptide chain from the ribosome. The protein phosphorylated by the lysate is known to be the only ME-180 phosphokeratin modulated by cyclic AMP, reflecting in vitro the differential modification of ME-180 keratins in vivo. PMID- 2578820 TI - 2'-Fluoro-2'-deoxypolynucleotides as templates and inhibitors for RNA- and DNA dependent DNA polymerases. AB - Poly(2'-fluoro-2'-deoxyadenylic acid) (poly(dAfl)) and poly(2'-deoxycytidylic acid) (poly(dCfl)) were tested as templates in DNA synthesis reactions catalyzed by Xenopus laevis oocytes DNA polymerase alpha, mouse cell DNA polymerase gamma and avian myeloblastis virus (AMV) reverse transcriptase. Poly(dAfl).(dT)12 can fully substitute for poly(rA).(dT)12 as template with DNA polymerase gamma, to 50% with reverse transcriptase, but was poorly recognized by DNA polymerase alpha. DNA synthesis by reverse transcriptase with poly(dCfl).(dG)12 as template was 50% of that with poly(rC).(dG).(dG)12. The use of 2'-fluoropolymers as templates was more efficient at 37 degrees C than at 25 degrees C. No appreciable differences on the fidelity of DNA synthesis by reverse transcriptase were observed when dCMP misincorporation was measured with poly(dAfl).(dT)12 or poly(rA).(dT)12 as template primers. Poly(C) and poly-2'-O-methylcytidylic acid had no significant effect on the reaction catalyzed by DNA polymerase gamma and reverse transcriptase, independent of the synthetic polynucleotide complex utilized as template. On the other hand, poly(dCfl) was an inhibitor when poly(rA).(dT)12 or poly(dA).(dT)12 were used as templates, but not when poly(dAfl).(dT)12 was employed. Analogous results have been obtained with activated DNA and AMV 70 S RNA as templates in the reverse transcriptase reaction. The inhibition by poly(dCfl) was noncompetitive with regard to TTP, poly(dA) and poly(rA). Xenopus laevis oocytes DNA polymerase alpha was not inhibited by poly(dCfl). PMID- 2578822 TI - Antigenic structure of histone H2B. AB - Antigenic determinants of histone H2B were localized using a series of 23 overlapping fragments of H2B obtained either by chemical and enzymatic cleavage of the histone or by solid-phase peptide synthesis. The ability of peptides to bind H2B antibodies was measured in an enzyme-linked immunosorbent assay, using antisera directed against calf thymus and chicken erythrocyte H2B as well as four anti H2B monoclonal antibodies obtained from autoimmune mice. Seven antigenic determinants were localized in the H2B molecule in the vicinity of residues 1-11, 6-18, 15-25, 26-35, 50-65, 94-113 and 114-125. Two of these determinants (residues 6-18 and 26-35) were revealed only through the binding properties of antibodies isolated from autoimmune mice. The usual correlation between hydrophilicity and antigenicity was found to hold for four of the epitopes, and the N- and C-termini of H2B were both antigenically active. PMID- 2578823 TI - Incorporation of 32P into phospholipids in vivo during compensatory renal growth. AB - Incorporation of 32P into phospholipids, RNA and DNA was studied in adult male C57BL/GoZgb mice. Left nephrectomy was performed under diethyl ether anesthesia, and the remaining right kidney was excised 10 min to 28 days later. Sham-operated animals were used as controls. 2 h before killing, animals were injected intraperitoneally with 37 kBq (1 microCi) 32P (as sodium orthophosphate) per g of body weight. In the right kidney, incorporation of 32P into total phospholipids, and five phospholipid fractions (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, diphosphatidylglycerol and sphingomyelin) was increased by 25 35% between 20 and 72 h after uninephrectomy. The incorporation of 32P into RNA showed a similar pattern. However, incorporation of 32P into phosphatidylinositol and phosphatidic acid was already increased 20 min after uninephrectomy, reached a peak about 110-120% above control values 4 h after uninephrectomy, and then slowly returned to the control value at about 84-96 h. These results indicate that an early alteration in phospholipid metabolism, particularly of inositol lipids, may play a role in initiation of compensatory renal growth. PMID- 2578824 TI - The binding of Ruthenium red to tubulin. AB - The inhibition of microtubule assembly by Ruthenium red (Deinum, J., Wallin, M., Kanje, M. and Lagercrantz, C. (1981) Biochim. Biophys. Acta 675, 209-213) could be counteracted by either taxol or dimethyl sulfoxide. Ruthenium red remained bound to the assembled microtubules. Microtubules assembled in the presence of Ruthenium red and taxol showed the typical taxol-dependent stability. The dimethyl sulfoxide-induced microtubules showed normal assembly characteristics, e.g., were GTP dependent, could be disassembled by cold, colchicine and Ca2+ and had no alterations in ultrastructure. The absolute disassembly induced by Ca2+ in the presence of dimethyl sulfoxide and Ruthenium red was dependent on the microtubule protein concentration, but independent in the absence of Ruthenium red. Ruthenium red was strongly bound to purified tubulin also in the presence of 8% (v/v) dimethyl sulfoxide. The dimethyl sulfoxide-induced assembly of purified tubulin in the presence of Ruthenium red was slightly stimulated, although the critical protein concentration was the same. It was found by resonance Raman spectroscopy with a flow technique that Ruthenium red did not bind to a specific calcium binding site on tubulin, although binding to a GTP binding site cannot be excluded. The wavenumbers of the lines in the region 375-500 cm-1 differ from those found for Ruthenium red bound to typical calcium-binding proteins such as calmodulin. Although Ruthenium red binds to serum albumin as well, the spectrum with albumin resembled that of the free dye. PMID- 2578825 TI - A solid-phase immunosorbent assay to determine the proteinase binding capacity of alpha 2-macroglobulin using 125I-trypsin as indicator proteinase. AB - Hyperimmune sera against human alpha 2 macroglobulin were raised in rabbits following immunization with 's' alpha 2-macroglobulin over half a year. Immunoglobulins were prepared by DEAE-Sephacel anion exchange chromatography. The immunoglobulin preparations showed a remarkably high and equal titer for 's' and 'f' alpha 2-macroglobulin (plasma alpha 2-macroglobulin fully saturated with pig pancreas trypsin), which amounted to 6.4 X 10(-6) as revealed by passive hemagglutination. Immunoimmobilization experiments revealed that at equilibrium, 's' alpha 2-macroglobulin and both 'f' alpha 2-macroglobulins (27 and 82% saturation of 's' alpha 2-macroglobulin with trypsin) had been bound to the same degree from the fluid phase to the monospecific antibodies that had been adsorbed to polystyrene tubes. Comparison of quantitative gel scans for disappearance of the intact alpha 2-macroglobulin subunit (Mr 182000) with 125I-labeled trypsin binding capacity of immunoimmobilized alpha 2-macroglobulin-trypsin complexes showed conspicuous agreement. Rocket immunoelectrophoresis did not give significant differences between 's' alpha 2-macroglobulin and 'f' alpha 2 macroglobulin. In the fluid phase, a binding ratio of 2.4 mol trypsin/mol alpha 2 macroglobulin was observed. Saturation of solid phase immunoimmobilized 's' alpha 2-macroglobulin with trypsin could be accomplished by incubation with a 100-200 fold molar excess of enzyme for 10 min. The solid-phase experiments showed a binding ratio of 2.0 mol trypsin/mol alpha 2-macroglobulin. The high molar excess of trypsin needed to saturate solid-phase immunoimmobilized alpha 2 macroglobulin, which binds 20% less trypsin than in the liquid phase, is partially explained by an enhancement of the negative cooperativity of trypsin binding to alpha 2-macroglobulin found in the liquid-phase system. Assessment of the trypsin-binding capacity of alpha 2-macroglobulin immunoadsorbed from synovial fluids (n = 19) of patients with seropositive rheumatoid arthritis yielded an inactive alpha 2-macroglobulin of 0-53% when compared to the trypsin binding capacity of normal plasma alpha 2-macroglobulin. PMID- 2578826 TI - alpha-Adrenergic stimulation of trans-sarcolemma electron efflux in perfused rat heart. Possible regulation of Ca2+-channels by a sarcolemma redox system. AB - The role of trans-sarcolemma membrane electron efflux in the alpha-adrenergic control of Ca2+ influx in perfused rat heart was examined. Electron efflux was measured by monitoring the rate of reduction of extracellular ferricyanide and compared with changes in contractility, as an indirect assessment of changes in cytoplasmic Ca2+ concentration. Methoxamine and phenylephrine each increased the rate of ferricyanide reduction from 80 to approx. 114 nmol/min per g wet wt. of heart, with half-maximal activation occurring at 10 microM for each agonist. Activation of the rate of ferricyanide reduction by both 10 microM methoxamine and 10 microM phenylephrine was blocked by the alpha-adrenergic antagonist, phenoxybenzamine, but not by the beta-antagonist, propranolol. Stimulation of the rate of ferricyanide reduction by the alpha-agonist coincided with the increase in contractility, each reaching maximum values at approx. 80 s. Removal of the alpha-agonists led to parallel decreases in contractility and the rate of reduction, each returning to pre-stimulation values in approx. 400 s. In addition, the relationship between Ca2+ and ferricyanide reduction was examined. Perfusion of the heart with medium containing 6 mM CaCl2 significantly increased contractility and the rate of ferricyanide reduction. Perfusion of the heart with low Ca2+ diminished contractility, did not affect the rate of ferricyanide reduction, but amplified the stimulatory effect of methoxamine on this rate. The increase in ferricyanide reduction by alpha-adrenergic agonists resulted from a change in the apparent Vmax, indicative of an increase in electron efflux sites in the plasma membrane. It is concluded that alpha-adrenergic control of electron efflux closely parallels changes in contractility and therefore changes in the cytoplasmic concentration of Ca2+. The data suggest that alpha-agonist-mediated changes in electron efflux may lead to Ca2+ influx. PMID- 2578827 TI - The effects of gamma-hexachlorocyclohexane on amylase secretion and inositol phospholipid metabolism in mouse pancreatic acini. AB - Dispersed mouse and guinea-pig pancreatic acini were used to examine the effects of the inositol analogue, gamma-hexachlorocyclohexane (lindane) on agonist stimulated amylase secretion. Secretion from mouse acini in response to carbachol and cholecystokinin octapeptide (CCK-8) was reduced by lindane. Similarly, amylase release from guinea-pig acini stimulated by carbachol was abolished by lindane. These acini, however, still remained responsive to dibutyryl-cAMP with only a slightly diminished secretion to this agent. Inositol phospholipid synthesis and hydrolysis was stimulated in mouse acini by both carbachol and CCK 8. Although hydrolysis of these lipids in response to CCK-8 was reduced by only 18%, stimulation of inositol phospholipid synthesis by either agonist was abolished by lindane. Dose-response curves for inositol phospholipid synthesis stimulated by carbachol and CCK-8 in mouse acini were biphasic and superimposable with those of amylase secretion. In contrast, the dose-response curve for phosphoinositide hydrolysis was sigmoid and clearly separable from that of synthesis. Reducing the external Ca2+ concentration caused the dose-response curves for carbachol- and CCK-8-induced inositol phospholipid synthesis to be displaced to the right, as has been observed for amylase secretion. A23187 was also found to induce amylase secretion and inositol phospholipid synthesis, and both of these responses were inhibited by lindane. Amylase secretion and inositol phospholipid synthesis may, therefore, be closely related events in the exocrine pancreas. Lindane may provide a valuable tool with which to determine the role of inositol phospholipid metabolism in stimulus-response coupling. PMID- 2578828 TI - Interaction of T-2 toxin and murine lymphocytes and the demonstration of a threshold effect on macromolecular synthesis. AB - Although T-2 toxin intoxications have been described as radiomimetic, we find that T-2 toxin does not preferentially affect multiplying cells. Among the targets of T-2 toxin toxicity, DNA, RNA and protein synthesis inhibition are analysed. All three types of macromolecular syntheses are affected by a threshold dose of T-2 toxin which corresponds to the interaction of approx. 1 X 10(5) T-2 toxin molecules with the same number of T-2 toxin receptors (Gyongyossy-Issa, M.I.C. and Kachatourians, G.G. (1984) Biochim. Biophys. Acta 803, 197-202). Since toxic effects occur faster at higher toxin concentrations than at lower levels, the time-toxic effect relationship may be defined by a constant. Based on these observations, we hypothesize that complete receptor-occupation is the critical first step in the course of T-2 toxin toxicity events. PMID- 2578829 TI - Cerebrospinal fluid magnesium and calcium related to amine metabolites, diagnosis, and suicide attempts. AB - Magnesium and calcium concentrations were measured in the cerebrospinal fluid (CSF) of 15 neurological controls and 41 psychiatric patients suffering from major depression (n = 16), schizophrenic disorder (n = 15), or adjustment disorder (n = 10). All subjects were women 19-67 years of age and free from drugs at the time of the study. CSF was evaluated for 5-hydroxyindoleacetic acid (5 HIAA), homovanillic acid (HVA), and cortisol (CS) levels, and all patients received a dexamethasone suppression test (DST) following lumbar puncture. CSF calcium levels did not differ among groups, although we found a trend toward higher mean levels in both depression and schizophrenia. By contrast, CSF magnesium was found to be significantly lower in both depression and adjustment disorder; if, however, patients who had made suicide attempts were excluded, the difference became insignificant. Patients who had made suicide attempts (by using either violent or nonviolent means) had significantly lower mean CSF magnesium level irrespective of the diagnosis. CSF calcium did not correlate with magnesium, 5-HIAA, HVA, CS, global severity, therapeutic response, or DST, but CSF magnesium correlated significantly with CSF 5-HIAA, especially after correcting for age and body height. Both variables seemed to be primarily related to recorded suicide attempts, but decreased magnesium was not limited to violent cases. PMID- 2578831 TI - Self-excitation in a porous membrane doped with sorbitan monooleate (Span-80) induced by an Na+/K+ concentration gradient. AB - The electrical potential across a fine-pore membrane doped with sorbitan monooleate (Span-80) imposed between aqueous solutions of NaCl and KCl was studied. It was found that this system showed rhythmic and sustained oscillations of electrical potential between the two aqueous solutions. These oscillations were attributed to the change of permeability of Na+ and K+ across the membrane, which originated from the phase transition of Span-80 molecules within the fine pores. Impedance measurement across the membrane also suggested a change in permeability. It was found that this membrane exhibited the property of differential negative resistance. In relation to this, it was shown that Na+ and K+ have different effects on the aggregation of Span-80 molecules. The mechanism of oscillation is discussed in relation to the ability of Span-80 molecules to behave as a dynamic channel through the membrane. This oscillatory phenomenon is interesting because in biological nervous membranes a difference between the concentrations of Na+ and K+ across the membranes is essential for excitability. PMID- 2578830 TI - Anticomplementary activity of dextran derivatives. AB - Substitution with carboxylic and benzylamine sulphonated groups conferred on dextran both antithrombic activity and the capacity to inhibit formation of the amplification C3 convertase of complement. In dextrans substituted with carboxylic groups (greater than 40%), a high content of sulphonate (greater than 10%) resulted in both anticomplementary and antithrombic properties whereas a lower content of sulphonate resulted in high anticomplementary but weak antithrombic activity. The anticomplementary activity of highly substituted dextrans was similar to that of heparin, although anticoagulant activity was much lower than in heparin, confirming independent structural requirements for both activities in the heparin molecule. PMID- 2578833 TI - [Protein, RNA and DNA synthesis in skin fibroblast cultures from healthy donors and patients with rheumatic diseases]. AB - Synthesis of protein, RNA and DNA was studied in skin fibroblast cultures of healthy donors and patients with systemic scleroderma (SSD) and in those with rheumatoid arthritis (RA) with the use of 14C-protein hydrolyzate, 14C-uridine and 14C-thymidine, respectively. A study was also made of the stimulation of 14C proline incorporation in protein fibroblasts upon addition to serum-free media of 5% bovine embryonic serum. The stability of RNA in fibroblasts was tested. It was shown that the rate of protein synthesis was 11 times higher in fibroblasts of RA patients and 6 times higher in those of SSD patients as compared to the rate of protein synthesis in fibroblasts of normal subjects. The rate of DNA synthesis in skin fibroblasts of RA patients was 15 times higher and in those of SSD patients 4 times higher than normal. In both RA and SSD patients, the synthesis of short labeled RNA was 2-3 times higher than normal. The addition of embryonic serum increased 2-3 times the incorporation of 14C-proline in protein skin fibroblasts of SSD patients. It was found that all RNA in skin fibroblasts was represented by long-living molecules and that 30-40% of short-labeled RNA in skin fibroblasts of healthy donors and SSD patients underwent degradation within 1-2 hours. The data obtained indicate that fibroblasts of the two pathologies under study are characterized by considerable differences in the synthesis of DNA and the activity of the protein-synthesizing system. PMID- 2578832 TI - Complex membrane transport systems. A non-Markovian approach. AB - This paper suggests a method of how to deal with complex membrane transport systems such as ion channels or ion pumps formed by proteins. The complexity of these systems results from the fact that proteins may undergo an internal dynamics of conformational changes and may thereby affect the transmembrane transport. Usually, complex transport systems are mapped into multi-state graphs and couched in terms of Markovian master equations. It is shown in this paper how the dimensionality of such multi-state systems can be reduced. The resulting description may be expressed in the form of a generalized master equation with a memory function as integral kernel. The memory function reflects the protein's own dynamics and its overall effect on the transport. This formalism, non Markovian in nature, is applied to describe the time-dependent action of ion pumps. A general model is constructed on the basis of the rate theory which contains all the essential parts of ion pumps such as a catalytic unit and a channel-like conduit for ion translocation and which is still analytically tractable. The short-time behaviour of the pumping process turns out to be of particular interest, since it reveals the dynamics of the catalytic unit itself. A strong correlation of the particle's motion over times less than a certain correlation time has been found. This result is compared with experimental findings on the proton pump of Halobacterium halobium. It is concluded that such a perfect short-time memory could be a generic property of active transport systems. PMID- 2578834 TI - [Immunoenzyme determination of neurospecific antigen 10-40-4 in human and animal tissue and organ extracts]. AB - IEA of brain specific antigen 10-40-4 in human and animal organs and tissues was elaborated. The method permits measuring the concentration of the antigen within the range from 1 to 120 ng/ml. The use of the method made it possible to confirm brain specificity of protein 10-40-4, since its brain content is 1500 to 2000 times higher than in other organs, and to estimate the percentage of cross reaction between antigenic determinants of brain specific antigen 10-40-4 from different species of animals. PMID- 2578835 TI - [Determination of antibodies to Streptococcus group A polysaccharide in human sera by an immunoenzyme method]. AB - Use was made of the ELISA to develop a highly sensitive quantitative method for detection of antibodies against Streptococcus group A polysaccharide (polysaccharide A) in human sera. The main advantage is that one can use only one optimal dilution of the sera together with the reference serum. Sera of 53 healthy volunteers and 77 patients with a history of Streptococcus group A infections were screened for the presence of polysaccharide A antibodies. Highly reproducible results were obtained in 97% of cases. The specificity of the method was shown with the polysaccharide A-induced inhibition of the reaction. Positive reactions obtained with the tested sera in gel immunodiffusion correlated with the data derived by the ELISA. Using the latter high level of specific antibodies was found in some of the sera that yielded negative reactions when tested by gel immunodiffusion. This may be associated with the presence of non-precipitating antibodies. PMID- 2578836 TI - [Histogenesis of skeletogenic tissue in bone regeneration during distraction]. AB - Light and electron microscopy were employed to study the histogenesis of the skeletogenous tissue during stable distraction osteosynthesis according to G. A. Ilizarov. Osteosynthesis proceeded on the basis of the invariably existing fibrillar connective tissue growth plate situated in the medium part of the distraction regenerate. Osteogenesis was continuously accompanied by angiogenesis. Preservation of the connective tissue plate is accounted for by the stimulating influence of distraction on fibrillogenesis. The authors suggest the common character of the histogenesis of the vascular and bone tissues in the connective tissue blastema of the interfragmental distraction regenerate. PMID- 2578837 TI - Increased expression of a novel c-abl-related RNA in K562 cells. AB - The c-abl locus is translocated from chromosome 9 to chromosome 22 in chronic myelogenous leukemia (CML), creating the Philadelphia chromosome (22q-, Ph1), one of the most consistent chromosomal abnormalities found in human hematologic malignancy. The K562 cell line is a human cell line originally derived from a patient with CML. We have isolated cloned human c-abl probes to analyze the organization and expression of abl genes in patients with CML and in K562 cells. With these probes, we confirm the amplification of abl genes in K562 cells. In addition, we demonstrate the presence of increased amounts of a novel RNA species hybridizing to a c-abl probe in K562 cells. This same large RNA species is present in addition to two normal transcripts in the leukemic cells of patients with CML. These results provide evidence that the c-abl locus is abnormally expressed in CML. PMID- 2578838 TI - Lysis of lymphoma cells by autologous and allogeneic natural killer cells. AB - Studies were undertaken to determine whether natural killer (NK) cells would lyse autologous and allogeneic lymphoma cells. When large granular lymphocytes, which are known to mediate NK activity, were enriched from peripheral blood and used as effector cells, they lysed autologous lymphoma cells of all of eight patients tested, and those of healthy donors lysed lymphoma cells of all of ten patients tested. The addition of interferon to the culture medium enhanced their cytotoxicity in three of the eight patients in the autologous effector-tumor system and in four of the ten patients in the above allogeneic system. On the basis of the unlabeled target competition test and the decrease in cytotoxicity with anti-NK antibody treatment, NK cells appeared to be the main cytotoxic effector cells for autologous and allogeneic lymphoma cells. PMID- 2578839 TI - Amphotropic retrovirus vector transfer of the v-ras oncogene to human hematopoietic and stromal cells in continuous bone marrow cultures. AB - Human continuous bone marrow cultures were established from intraoperative marrow specimens and infected with amphotropic murine leukemia virus (Am-MuLV) pseudotypes of Kirsten or Harvey murine sarcoma virus, and the biologic effects were compared with mouse continuous bone marrow cultures. Cultures were tested for production of total nonadherent granulocytes and granulocyte-macrophage progenitor cells (GM-CFUc); virus replication by supernatant reverse transcriptase activity; percentage of adherent and nonadherent cells and GM-CFUc that released virus by infectious center assay; and for synthesis of Harvey ras p21 protein. High-efficiency, stable Am-MuLV infection of over 90% of human marrow-culture nonadherent and adherent cells and both seven- and 14-day GM-CFUc were detected as Kirsten or Harvey pseudotype virus release by infectious center assay. Synthesis of Harvey ras p21 was detected in the adherent and nonadherent cell populations of human as well as mouse continuous marrow cultures infected with Kirsten or Harvey pseudotype virus. In contrast to data with mouse cultures, cumulative production of GM-CFUc and differentiated granulocytes in human cultures was not detectably altered by Harvey or Kirsten virus infection, and all cultures ceased to produce hematopoietic cells by 20 weeks. Of 54 virus-infected cultures in ten separate experiments, 13 produced a second peak of nonadherent cells (greater than 10(5) per flask) after 20 weeks, significantly more frequently than did control uninfected cultures (one of 32). When subcultured, these harvests produced permanent Epstein-Barr virus (EBV)-transformed pre-B cell lines that released the original inoculating pseudotype virus. Thus, Am-MuLV is a potentially valuable vector for inserting genetic sequences by recombinant techniques into human hematopoietic and stromal cells in culture; however, activation of EBV may be a significant complication. PMID- 2578840 TI - Small cell lung cancer, endocrine cells of the fetal bronchus, and other neuroendocrine cells express the Leu-7 antigenic determinant present on natural killer cells. AB - Small cell lung cancer is distinguished from other lung cancer histologic types by possessing a variety of neuroendocrine properties. Anti-Leu-7 is a monoclonal antibody that recognizes a 110,000-dalton molecular weight glycoprotein initially described on natural killer cells and subsequently reported on a variety of normal and malignant neural and neuroendocrine cell types. We have found intense anti-Leu-7 binding to a large number of small cell lung cancers, while other lung cancer types were negative or showed only weak and focal binding. Other antigens expressed by natural killer cells, lymphocytes, and monocytes were never or less often expressed on small cell lung cancer cells. In addition, we report for the first time anti-Leu-7 binding by carcinoids, carotid body tumors, pheochromocytomas, endocrine cells of the fetal bronchus and the adult intestine, and select pancreatic islet cells. Anti-Leu-7 binding by small cell lung cancer is consistent with a derivation from pulmonary precursor cells, and anti-Leu-7 staining is clinically useful for the identification of human neuroendocrine tumors of the amine precursor uptake and decarboxylation ("APUD") type. PMID- 2578841 TI - High-dose intravenous gamma globulin in alloimmunized platelet transfusion recipients. PMID- 2578843 TI - CFU-F from dog marrow: a colony assay and its significance. AB - A colony assay method is described for studying dog fibroblast colony development in marrow cells derived from resected ribs. The assay showed an increased number of fibroblast colony forming units (CFU-F) in cell suspensions prepared from resected ribs compared to cell suspensions prepared from bone marrow aspirates or from peripheral blood. A linear relationship between the number of cells plated and the number of fibroblastoid colonies was demonstrated in each case. The proportion of phagocytic cells was lower in cultures prepared from resected ribs than in those prepared from bone marrow aspirates. Staining for acid phosphatase and with sudan black showed differences between phagocytic cells and non phagocytic fibroblasts. When left in plastic dishes for 2 hrs, 81% +/- 10% of the CFU-F adhered to the plastic dishes. Velocity sedimentation separation showed a modal sedimentation rate of 6.49 mm/h. PMID- 2578842 TI - Sudanophilia of rat lymphocytes. AB - A significant proportion of large lymphocytes in laboratory rats is stained with Sudan black B. The increase in the counts of sudanophilic blood lymphocytes over control values indicated reliably the recovery of lymphocytic function even when total lymphocyte, small or large lymphocyte counts were normal or reduced. PMID- 2578844 TI - Carbaryl inhibition of interferon synthesis in cultured goldfish cells. PMID- 2578845 TI - Psychosomatic medicine and the problem of meaning. PMID- 2578846 TI - Immunocytochemical localisation of prostate-specific antigen: specificity and application to clinical practice. AB - An immunocytochemical method to localise prostate-specific antigen (PSA) in paraffin sections was used to establish the prostatic origin of both primary and metastatic tumours. The specificity of the technique was confirmed in 65 known primary (63 PSA-positive) and 17 metastatic prostatic carcinomas (16 PSA positive). Thirteen non-prostatic primary carcinomas and a series of benign proliferative and malignant conditions which might be considered in the morphological differential diagnosis of prostatic adenocarcinoma were PSA negative. The technique has now been applied diagnostically to tumour tissue resected from 21 patients. These neoplasms of the base and neck of the bladder could not be categorised as prostatic or urothelial in origin by clinical and endoscopic assessment or by conventional histopathology. In 11 patients such tumours were PSA-positive, indicating a prostatic origin. In two further patients, the prostatic origin of lymph node secondaries was confirmed in the absence of a clinically apparent primary. The technique is a valuable adjunct to conventional histopathology. PMID- 2578847 TI - Prostatic biopsy with the 21 gauge Surecut needle. A preliminary report of a new technique. AB - The 21 gauge Surecut needle is a fine needle system providing regular tissue cores for histological evaluation. Using the Franzen needle sheath, transrectal biopsies were performed on 13 patients and a tissue core obtained in 12 cases. Ultrasonically guided transperineal biopsies were performed on 14 patients and a tissue core was obtained in 13 cases. It is concluded that the 21 gauge Surecut needle is able to yield histological material for prostatic diagnosis. PMID- 2578848 TI - Interferons and natural killer cells. PMID- 2578849 TI - Fetal haematology in rhesus isoimmunisation. AB - Haematological studies were carried out in pure fetal blood samples obtained fetoscopically in 29 rhesus isoimmunised pregnancies at 18-24 weeks' gestation, and the values were compared with those obtained in 62 normal control pregnancies. Fetal reticulocytosis or erythroblastaemia was seen only in association with a haemoglobin concentration of 4 g/dl or less. Ten of the 14 fetuses with a haemoglobin concentration below 4 g/dl showed ultrasonographic evidence of hydrops. PMID- 2578850 TI - Onycholysis associated with cytotoxic drugs. PMID- 2578851 TI - Can we afford screening for neural tube defects. PMID- 2578852 TI - Screening for neural tube defects. PMID- 2578854 TI - Somatostatinergic neurons in the insular cortex project to the spinal cord: combined retrograde axonal transport and immunohistochemical study. AB - A double-labeling method combining immunohistochemistry and a retrograde tracer technique using biotin-horseradish peroxidase (B-HRP) was employed to identify a descending somatostatinergic fiber system from the insular cortex to the spinal cord. Injection of B-HRP into the spinal cord at cervical or lumbar levels resulted in the labeling of a number of neurons in the insular cortex. Simultaneous immunostaining revealed the existence of double-labeled neurons in the insular cortex. The result provides direct evidence for the presence of a descending somatostatinergic pathway from the insular cortex to lumbar levels of the spinal cord. PMID- 2578853 TI - Reversal of the static component of spindle potential by imposed depolarizing current in the frog muscle spindle. AB - The static component of the spindle potential provoked during stretch of isolated muscle spindles of the frog was reversed during the application of depolarizing currents ranging from 0.2 to 5 nA in normal Ringer solution and also in Na+-free Ringer solution. In the same range of current intensities, spontaneous rhythmic hyperpolarizations due to [Ca2+]i-activated GK, an attenuation of membrane impedance, and an anomalous decrease in amplitude of the afferent spikes were observed. All 4 phenomena were abolished by K+ channel blockers (10 mM CsCl, 1-2 mM 4-aminopyridine (4-AP), or 20 mM tetraethylammonium chloride (TEA], Ca2+ channel blockers (5-10 mM CoCl2, MnCl2, 1-2 mM CdCl2 or 0.5 mM verapamil) or 0.1 mM quinine. The amplitude of the static component of the spindle potential was markedly increased at threshold concentration of the K+ channel blockers (5 mM CsCl, 0.1-0.5 mM 4-AP or 5-10 mM TEA), but the component disappeared at that of the Ca2+ channel blockers. The rhythmic hyperpolarizations are associated with the spindle potential, except for its dynamic component, which often triggers a hyperpolarizing deflection. We suggest that both the static component of the spindle potential and rhythmic hyperpolarizations are due to GK(Ca) in the intracapsular axon, either along the terminal or at the branching nodes, or both; and that the receptor potential contributes to, but is not the same as, the spindle potential. PMID- 2578855 TI - The central distribution of vagal catecholaminergic neurons which project into the abdomen in the rat. AB - A double labeling technique employing retrograde labeling of vagal neurons with horseradish peroxidase from injections into the stomach wall and immunocytochemistry for dopamine-beta-hydroxylase revealed catecholaminergic neurons in the medulla oblongata which project into the abdomen. The great majority of such neurons were located in the dorsal motor nucleus of the vagus, particularly in its rostral third. PMID- 2578856 TI - Suicide transport of ricin demonstrates the presence of substance P receptors on medullary somatic and autonomic motor neurons. AB - Suicide transport of the toxic lectin, ricin, by hypoglossal and vagus neurons resulted in motor neuron loss in the associated nuclei, and reduced the binding of the 125I-Bolton-Hunter labeled substance P in the same nuclei. These data show that substance P receptors are located on the cell bodies of medullary somatic and preganglionic motor neurons of the hypoglossal and vagus nerves, and that suicide transport is a useful technique to determine the cellular localization of binding sites within a nucleus. PMID- 2578857 TI - Immunochemical detection of diverse molecular species of horseradish peroxidase recovered from rat superior cervical ganglion following retrograde transport. AB - The sympathetic innervation of the submandibular gland (SMG) by neurons of the superior cervical ganglion (SCG) was used as a model system to characterize the different molecular species of retrogradely transported horseradish peroxidase (HRP). Following injections of 3 mg of HRP into the SMG, enzymatically active HRP was demonstrated by histochemistry in SCG neurons for up to 14 days. Parallel immunochemical studies were conducted on electroblots of SCG homogenates from other rats subjected to similar SMG injections of HRP. This technique allowed the detection of nanogram amounts of HRP. These experiments demonstrated that an immunochemically detectable 40 Kd species of HRP was retrogradely transported and retained in SCG neurons for up to 6 days. Beyond 8 days, only lower molecular weight (15-30 Kd) immunoreactive breakdown products of HRP were observed in SCG homogenates. Similar spontaneous HRP breakdown products displayed enzymatic activity in non-denaturing gels. These studies suggest that retrogradely transported HRP is degraded by neurons to lower molecular weight species which retain enzymatic activity. We conclude that morphological studies of retrogradely transported HRP visualized by histochemical methods reflect the response of neurons to a variety of enzymatically active molecular forms of HRP. PMID- 2578858 TI - Changes of serotonin and dopamine metabolism in various forebrain areas of rats injected with morphine either systemically or in the raphe nuclei dorsalis and medianus. AB - The regional brain metabolism of serotonin (5-HT) and dopamine (DA) was studied in rats injected with morphine either systemically or in the nuclei raphe medianus (MR) or dorsalis (DR). A subcutaneous injection of 10 mg/kg morphine significantly raised the levels of 5-hydroxyindoleacetic acid (5-HIAA) in the diencephalon, striatum, nucleus accumbens and cortex with no effect in the hippocampus. Similar changes in 5-HT metabolism were found in animals injected with 5 micrograms/0.5 microliter in the DR whereas morphine injected in the MR raised 5-HIAA levels only in the nucleus accumbens. A subcutaneous or direct injection of morphine in the DR significantly raised the levels of homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) in the striatum and nucleus accumbens, but injection in the MR was ineffective. All the effects of morphine were blocked by naloxone, injected either intraperitoneally (1 mg/kg) or directly in the raphe nuclei (2 micrograms/0.5 microliter). Pretreatment with parachlorophenylalanine, an inhibitor of serotonin synthesis, significantly reduced the effect of morphine injected in the DR on dopamine metabolism in the striatum and nucleus accumbens. The data suggest that a major mechanism by which morphine increases 5-HT metabolism in the rat forebrain is activation of 5-HT cells in the nucleus raphe dorsalis, and this action may contribute to the increased DA metabolism found in the animal injected with morphine in this brain area. PMID- 2578860 TI - Biological response modifiers: their potential and limitations in cancer therapeutics. PMID- 2578861 TI - [Systemic or intracerebral injection of bovine neurointermediate lobe extracts may induce paradoxical sleep in insomnia induced by p-chlorophenylalanine in cats]. AB - Injections of Bovine neuro-intermediate lobe extracts, either subcutaneously (5 U), intraventricularly (20 mU) or directly in the vicinity of the nucleus magnocellularis of the medulla (1,3 mU) may induce paradoxical sleep in totally insomniac cats pretreated with P. chlorophenylalanine. PMID- 2578859 TI - Effects of chemotherapeutic agents on the immune response. II. PMID- 2578863 TI - Radiotherapy versus resection for palliation of carcinoma of the esophagus. PMID- 2578862 TI - [Inhibitory effect of human alpha 2-macroglobulin and a peptide released by trypsin, on the G1-S transition of hepatocytes in vivo]. AB - Highly purified human alpha 2 M inhibits hepatocyte proliferation. 1 mg of alpha 2 M corresponds to 1 baby rat unit (BRU). alpha 2 M is bound to a low molecular weight glycopeptide, which is released during trypsinization of alpha 2 M. 3 micrograms of trypsin-treated alpha 2 M release 1 BRU. alpha 2 M and the glycopeptide have been shown to be identical, respectively, to high and low molecular weight components present in normal human plasma. Both components inhibit the G1-S transition of the hepatocyte cycle. alpha 2 M acts as an antagonist to the inhibitory effect of the glycopeptide when the molar ratio of trypsin to alpha 2 M is greater than 2. PMID- 2578864 TI - Heroin and pain. PMID- 2578866 TI - Simultaneous detection of SCE and Q-bands on human chromosomes by a double staining technique. AB - Human lymphocytes were cultured for two cell cycles in the presence of bromodeoxyuridine (BrdU), and the resulting metaphase chromosomes were first stained with quinacrine mustard (QM) and then, immediately afterwards, with Hoechst 33258, without any intermediate destaining. Both Q-banding patterns and sister chromatid differential staining were photographed subsequently on the same metaphase using two different filter blocks of the fluorescence microscope. PMID- 2578865 TI - Value of splenectomy in non-Hodgkin's lymphoma. AB - A retrospective review of patients with non-Hodgkin's lymphoma (NHL) who underwent palliative splenectomy for splenomegaly, hypersplenism, or autoimmune complications was done. From 1970 through 1981, 46 patients had palliative splenectomy for splenomegaly alone (n = 3) or various hematologic abnormalities with (n = 35) or without (n = 8) splenomegaly. Splenectomy was performed for life threatening (n = 7), severe (n = 15), or mild (n = 24) symptoms/signs. The most common hematologic abnormalities were thrombocytopenia (platelet count less than 120,000/mm3; n = 38) and/or anemia (hemoglobin level less than 11.0 g/mm3; n = 29). Response to splenectomy was defined as greater than a threefold increase in preoperative platelet count and/or an increase in hemoglobin levels to greater than 11.0 g/mm3 in the first postoperative month. Four patients with thrombocytopenia did not respond, whereas 33 patients responded with greater than a sevenfold increase in platelet count. All four nonresponders died of complications of thrombocytopenia or progressive disease. Eighteen of 28 (64%) patients with anemia responded to splenectomy. Larger spleens (2000 g versus 1410 g; P less than 0.05) and lower platelet counts (42,000 versus 75,000; P less than 0.05) were found in all nonresponding patients. Responders and nonresponders could not be distinguished on the basis of age, sex, race, duration of disease or splenic involvement, primary site of disease, histopathologic findings, bone marrow or lymphangiogram results, or prior chemotherapy and radiotherapy. Patients with mild symptoms/signs were more likely to respond hematologically than patients with life-threatening or severe symptoms/signs (86% versus 54%; P = 0.06). For all patients, 2- and 5-year survival from the time of splenectomy was 44% and 26%, respectively. Median survival was 18 months (range, 1-144 months). Inability to reverse hematologic abnormalities was associated with poor survival. All nonresponding patients died within 36 months of surgery, whereas 5-year survival in responding patients was 40%. Nine of 30 patients (30%) who responded hematologically survived longer than 5 years, but this group of patients could not be distinguished from the remaining patients on the basis of age, sex, race, duration of disease or splenic involvement, primary site of disease, histopathologic features, bone marrow or lymphangiogram results, or prior chemotherapy and radiotherapy. Surgery was well-tolerated (mortality, 9%; morbidity, 21%). All surgical mortalities and 78% of complications occurred in patients operated on for life-threatening or severe symptoms/signs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2578867 TI - In the search for new anticancer drugs XI. Anticancer activity of nitroxyl labeled phosphoric N,N;N',N';N",N"-tris[1,2-ethanediyl]triamide(TEPA) and phosphorothioic N,N;N',N';N",N"-tris[1,2-ethanediyl]triamide(thio-TEPA) derivatives. AB - In order to further evaluate the effect of the nitroxyl moiety on the anticancer activity of nitroxyl labeled analogues of phosphoric N,N;N',N';N",N"-tris[1,2 ethanediyl]triamide (TEPA) and phosphorothioic N,N;N',N';N",N"-tris[1,2 ethanediyl]triamide (thio-TEPA), the activity of these compounds was compared in vivo, using murine lymphoid leukemia L1210, with the reduced forms of the drugs, i.e. the hydroxylamines and amine congeners. At optimum dose, all compounds were active. However, the nitroxyl containing compounds were more active than the corresponding reduced forms. An admixture of 4-hydroxy-2,2,6,6 tetramethylpiperidine-1-oxyl had no effect on the activity of thio-TEPA. Consequently, the nitroxyl moiety must be an integral part of the anticancer drug's structure in order to influence that drug's performance. PMID- 2578869 TI - Effects of interferon and gangliosides on growth of cultured human glioma and fetal brain cells. AB - Human beta-interferon (IFN) induced an antiviral state in two fetal brain and six glioma cell lines. The growth-inhibitory effect of IFN was most pronounced on three glioblastoma lines and least on fetal brain and oligodendroglioma cells; IFN growth inhibition of one schwannoma and one anaplastic cell line was intermediate between the two other groups. Thus, the growth-inhibitory effect of IFN generally correlated with the degree of anaplasia of the tissue from which the cells were derived. IFN (1000 units/ml) had to be present for 24 to 48 hr to have a significant inhibitory effect on growth of glioblastoma (12-18) cells. However, growth inhibition of 12-18 cells exposed to IFN for 3 days persisted for 3 weeks. Both sialic acid-N-acetylgalactosamine ganglioside and a mixture of normal human brain gangliosides (50 microM) inhibited growth of fetal brain (CHII) but not glioblastoma 12-18 cells. However, preincubation of cells with either sialic acid-N-acetylgalactosamine or a mixture of gangliosides did not augment the growth-inhibitory effects of IFN on either CHII or 12-18. These results indicate that gangliosides and IFN may be operating through different mechanisms to cause growth inhibition. PMID- 2578868 TI - Studies on circulating antibody against carcinoembryonic antigen (CEA) and CEA like antigen in cancer patients. AB - Characteristics of auto-antibodies for carcinoembryonic antigen (CEA) detected in sera from 3 cancer patients (2 colorectal and 1 breast cancer) were examined. The antibodies belonged to polyclonal immunoglobulin G (IgG). The binding of auto antibodies with the labeled CEA was inhibited by not only the unlabeled CEA but also NCA-2 (feces and meconium). However, no binding with NCA was observed. Among these auto-antibodies the antibody directed against blood group Lewis determinants which are known to be present in many purified CEA preparations was not found. Previously we had suggested that CEA, NCA-2 and NCA may contain immune determinant in common with alpha 1-acid glycoprotein (AG). These auto-antibodies showed significantly enhanced reactivity for the labeled CEA preparation after purification by anti-AG affinity chromatography in spite of no immunological reaction with AG. These results suggest that auto-antibodies are raised against the common antigenic determinants of both CEA and NCA-2 which do not exist in NCA. These antibodies might be directed to common amino acid sequence shared by CEA and NCA-2, though not excluding the carbohydrate moiety. We surveyed about 500,000 cancer patients but could find only 3 patients who showed a difference in the values of CEA by the indirect and direct method. Thus, the existence of this type auto-antibody to CEA in cancer patients is a rare phenomenon. PMID- 2578870 TI - Enhanced polyglutamylation of aminopterin relative to methotrexate in the Ehrlich ascites tumor cell in vitro. AB - The polyglutamylation of aminopterin and methotrexate (N10-methylaminopterin) was compared in the Ehrlich ascites tumor in vitro. Three poly-gamma-glutamyl conjugates of methotrexate and aminopterin were detected, although at an equal (1 microM) extracellular drug concentration, the net accumulation of aminopterin polyglutamates exceeded that for the methotrexate polyglutamyl derivatives by a factor of 9. When compensation was made for transport differences between these compounds by adjusting the extracellular drug concentrations to achieve equivalent intracellular monoglutamyl substrate levels, the polyglutamylation of aminopterin was still 2.8-fold greater than that for methotrexate, suggesting that aminopterin is a better substrate for the folylpolyglutamate synthetase as well as the transport carrier. An additional metabolite of aminopterin was detected within seconds following drug exposure. This derivative did not bind tightly to dihydrofolate reductase, yet it was rapidly converted to a polyglutamate. The formation of both aminopterin polyglutamates and these novel derivatives was enhanced by increases in the free intracellular level of aminopterin. Aminopterin polyglutamates were bound tightly to dihydrofolate reductase and were retained intracellularly relative to unaltered aminopterin when Ehrlich cells containing these forms were suspended in drug-free medium. These findings support a role for the polyglutamylation of aminopterin as a critical element in drug action and as a factor in addition to membrane transport in the disparate antifolate potencies of aminopterin and methotrexate. PMID- 2578871 TI - Characteristics of the formation and membrane transport of 7-hydroxymethotrexate in freshly isolated rabbit hepatocytes. AB - The cellular pharmacology of methotrexate was evaluated in freshly isolated rabbit hepatocytes in suspension with an analysis of drug metabolism by high performance liquid chromatography. After exposure of hepatocytes at a cytocrit of 5% to 5 microM [3H]-methotrexate, intracellular 7-hydroxymethotrexate appears rapidly within the cell; within 15 sec, the level of 7-hydroxymethotrexate exceeds the level of intracellular methotrexate, although the latter has not achieved the dihydrofolate reductase binding capacity. Within 20 min, virtually all methotrexate is hydroxylated. There is minimal formation of methotrexate polyglutamyl derivatives even after exposure of cells to very high levels of methotrexate, and 7-hydroxymethotrexate polyglutamates do not accumulate in the cell at all after incubation with [3H]-7-hydroxymethotrexate. Because of the rapidity of the hydroxylation of methotrexate, transport of this agent could not be characterized. However, some aspects of the transport properties of 7 hydroxymethotrexate could be studied since the catabolite is neither bound nor metabolized in this system. Net 7-hydroxymethotrexate transport was reduced by the addition of 5-formyltetrahydrofolate. As observed for 4-aminoantifolate transport in other cell systems, net 7-hydroxymethotrexate transport was markedly stimulated by sodium azide, an inhibitor of energy metabolism. The data suggest that hydroxylation of methotrexate proceeds at a rate at least comparable to the rate of association of the drug with dihydrofolate reductase and that transport of methotrexate into rabbit hepatocytes is slow relative to the rate of catabolism to the 7-hydroxy derivative. Rabbit hepatocytes may be a useful model for exploring methotrexate catabolism at the cellular level and may provide insights into the interaction between methotrexate and/or other 4 aminoantifolates and the human liver. PMID- 2578872 TI - Origin and cytotoxic properties of base propenals derived from DNA. AB - Base propenals arise from DNA by a Fe(II)-bleomycin-mediated reaction which leads to strand scission. These compounds undergo addition-elimination reactions with thiols and other nucleophilic groups under physiological conditions and form an addition product with glutathione. Thymine- and adenine-N1-propenals inhibit DNA synthesis in HeLa cells; both compounds are cytotoxic [50% inhibiting concentration (IC50) = 1 to 2 microM]. A structurally related nucleoside, thymidine-N3-propenal, designed as a metabolic pathway inhibitor, inhibits growth of HeLa, L1210 leukemia, Lewis lung carcinoma, B16 melanoma, and DLD-1 human colon carcinoma cells in culture (IC50 = 1 to 6 microM). A single injection of this compound, administered on the first day following transplant of L1210 leukemia cells, increased the mean survival time of mice by 50% (T/C = 154). Thymidine-N3-propenal selectively blocks DNA synthesis in HeLa cells and inhibits thymidine kinase (Ki = 5.1 microM) and DNA polymerase-alpha. We suggest that base propenals, rather than damaged DNA, account for some of the cytotoxic effects of bleomycin and that nucleoside propenals represent a novel class of site-directed inhibitors. PMID- 2578873 TI - Effect of glutathione depletion on the hepatotoxicity and covalent binding rat liver macromolecules of N-hydroxy-2-acetylaminofluorene. AB - Glutathione plays an important role in the protection of the liver against several hepatotoxins. The hepatocarcinogen N-hydroxy-2-acetylaminofluorene is converted in the rat in vivo to reactive metabolites that bind covalently to cellular macromolecules. These metabolites may also react with glutathione, resulting in the formation of glutathione conjugates and in the detoxification of reactive metabolites. The role of glutathione in detoxification was investigated by depletion of glutathione in the rat in vivo with diethyl maleate. When rats were pretreated with diethyl maleate, 45 min before the administration of N hydroxy-2-acetylaminofluorene, excretion of 2-acetylaminofluorene:glutathione conjugates in bile was decreased by 60% as compared to controls. However, total covalent binding to rat liver protein was not increased, and total binding to DNA was even decreased (p less than 0.1), apparently at the expense of the acetylated carcinogen-DNA adducts. Formation of deacetylated, 2-aminofluorene adducts to DNA was not affected by diethyl maleate. Pretreatment with diethyl maleate had no major effect on the acute hepatotoxic effects of N-hydroxy-2-acetylaminofluorene. The results indicate that glutathione does not play a vital role in the detoxification of reactive metabolites generated from the carcinogen N-hydroxy-2 acetylaminofluorene, since glutathione is not very effective in competing with macromolecules for trapping of reactive metabolites of N-hydroxy-2 acetylaminofluorene. Thus, 1 mM glutathione did not decrease the covalent binding of 2-acetylaminofluorene-N-sulfate (one of the main reactive metabolites that is formed in vivo) to DNA in vitro, while 10 mM glutathione decreased the covalent binding to RNA by only 20% and to DNA by only 40%. PMID- 2578874 TI - Binding of chromium to chromatin and DNA from liver and kidney of rats treated with sodium dichromate and chromium(III) chloride in vivo. AB - The in vivo binding of chromium to whole chromatin, polynucleosomes, DNA, and cytoplasmic RNA-protein fraction from liver and kidney was examined after treatment of rats with sodium dichromate and chromium(III) chloride. Significant amounts of chromium were bound to DNA and the nonhistone proteins of chromatin and to cytoplasmic RNA-protein fraction. The binding of chromium to the nuclear and cytoplasmic nucleic acid fractions varied considerably, depending on the tissue and the oxidation state of the chromium administered. The level of chromium bound to whole chromatin was greater in the liver than in the kidney after treatment with either chromium compound. Chromium entered the liver and kidney tissues at a slower rate after chromium(III) treatment than after chromium(VI) treatment. At early times after chromium(VI) treatment, more chromium was bound to the liver and kidney chromatin and DNA than after chromium(III) treatment. A much smaller proportion of the chromium bound to chromatin was associated with the DNA after treatment with chromium(III) than after treatment with chromium(VI). However, 40 hr after injection, there was no significant difference in the level of chromium on the DNA from both the liver and kidney of chromium(VI)- and chromium(III)-treated animals. No DNA damage was detected in either liver or kidney nuclei after chromium(III) treatment, using the technique of alkaline elution. A possible correlation between chromium binding to chromatin and DNA damage is discussed. PMID- 2578875 TI - Topographical analysis of tumor-associated antigens on bovine leukemia virus induced bovine lymphosarcoma. AB - Tumor-associated antigens (TAAs) expressed on tumor cells from cattle with enzootic bovine leukosis were divided into three groups by using 13 monoclonal antibodies: common TAA; partially common TAA; and individually distinct TAA. TAA was extracted from tumor cells and purified by ion exchange chromatography on diethylaminoethyl-cellulose and isoelectric focusing. The common TAA, which was detected on all tumors tested, was eluted with 0.6 M KCl in ion exchange chromatography on diethylaminoethyl-cellulose, and the isoelectric point of the antigen was 6.8. The partially common TAA, which was detected on some (but not all) of the tumors tested, was eluted with 0.4 to 0.8 M KCl, and the isoelectric points of the antigen were 5.3, 5.8, and 6.4. The individually distinct TAA was present in the fractions eluted with 0.4 to 0.8 M KCl, and the isoelectric point of the antigen was 5.5. Results of competitive binding assay and Western blot analysis showed that the common TAA was a polypeptide with a molecular weight of 74,000; that it has at least two independent antigenic regions; that the partially common and individually distinct TAAs were a polypeptide with a molecular weight of 64,000; and that the antigenic determinants on the common TAA, partially common TAA, and individually distinct TAA existed independently from each other. PMID- 2578876 TI - Intermediate filament and cross-linked envelope expression in human lung tumor cell lines. AB - Human lung tumor cell lines established from the major histological types of lung cancer were examined by immunofluorescent staining techniques for their patterns of intermediate filament (keratin, vimentin, and neurofilament triplet protein) expression. All cell lines examined, both small cell lung carcinoma (SCLC) and non-SCLC (squamous cell carcinoma, adenocarcinoma, large cell carcinoma, and mesothelioma) contained keratin, consistent with their epithelial derivation. These lung carcinoma cell lines also expressed vimentin, the characteristic intermediate filament of mesenchymal cells in vivo. In light of the proposed neuroectodermal origin of SCLC, cell lines were also studied for neurofilament expression. Two of four SCLC tumor cell lines, as well as non-SCLC cell lines, showed no reactivity with antibodies to neurofilament triplet protein. Two of the SCLC cell lines stained weakly with anti-neurofilament antibody. Examination of specific keratin patterns in human lung tumor cell lines by selective immunoprecipitation with keratin antiserum and sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated that small-sized keratin proteins (Mr 44,000 to 52,000) were present in cell lines derived from SCLC and non-SCLC types of lung cancer. Tumor cell lines exhibiting squamous differentiation by light microscopic criteria (i.e., intracellular keratin, intercellular bridging, "pearl" formation, and/or individual cell keratinization) also displayed a preponderance of intermediate-sized keratins (Mr 57,000 and 59,000) and exhibited another feature of terminal keratinocyte differentiation (cross-linked envelope formation). Mesothelioma cell lines had varying keratin profiles. The presence of keratin proteins in all SCLC cell lines examined argues against a neuroectodermal origin for these tumors and is consistent with the notion that these tumors arise from a common bronchial "stem cell," similar to that from which other types of bronchogenic carcinomas arise. PMID- 2578877 TI - Two mouse monoclonal antibodies detecting two different epitopes of an activated lymphocyte antigen on adult T-cell leukemia cells. AB - Mouse monoclonal antibodies were produced against MT-2 cell line derived from adult T-cell leukemia or human T-cell leukemia virus-rich fraction therefrom. Two IgG1 antibodies, Ta60a and Ta60b, were found to be reactive not only with cell lines derived from adult T-cell leukemia or cutaneous T-cell lymphomas, but also with activated peripheral blood lymphocytes, suggesting the similarity of Ta60 antigen group to Tac antigen which is present on interleukin 2 receptor. Thus, the relationship among these antigens was studied. Two Ta60 antibodies and Tac antibody immunoprecipitated the molecule with almost identical electrophoretic mobility, approximately a Mr 60,000 antigen from [3H]glucosamine-labeled activated peripheral blood lymphocytes or MT-2, MT-1, or ATN-1 cells from adult T cell leukemia and a Mr 53,000 antigen from HUT-102 cells derived from cutaneous T cell lymphomas. Further, Tac antibody was found to immunoprecipitate Ta60b molecule on 125I-labeled MT-2 cells by sequential immunoprecipitation, indicating that these two epitopes are on the same molecule. Antibody binding inhibition assays with either 3H-labeled Ta60a or Ta60b antibody demonstrated that Ta60a and Tac are the same epitope, but different from Ta60b. Thus, at least two epitopes were demonstrated to be present on interleukin 2 receptor molecule. However, Ta60b antibody showed almost no blocking effects on proliferation of an interleukin-2-dependent cell line, whereas Ta60a antibody did. Various hematopoietic tumor cells were typed with these two antibodies, but the results with Ta60b antibody were described, because they showed a similar specificity. Ta60b antibody reacted with all adult T-cell leukemia cases, but did not react with T-cell acute lymphoblastic leukemia, lymphoblastic lymphoma, or mature T cell lymphoma. Interestingly, 3 of 12 acute myeloblastic leukemia and 2 of 5 chronic myelocytic leukemia in blastic crisis showed positive reactions. One third of B-cell chronic lymphocytic leukemia and B-cell lymphoma as well as a few B-cell lines were also weakly reactive with this antibody. A part of the results with direct tests was confirmed by the absorption tests. The results obtained demonstrated the presence of Ta60b on a certain fraction of malignant hematopoietic cells of other than T-cell origin. PMID- 2578878 TI - Direct and indirect effects of interferon on in vivo murine tumor cell growth. AB - We cloned two sublines (S1 and R1) of murine Meth A fibrosarcoma cells with respect to their sensitivity to a murine alpha/beta-interferon (IFN) preparation. The growth of S1 cells was suppressed and that of R1 cells was hardly affected by IFN in vitro. This was also the case with cells enclosed in cell-impermeable diffusion chambers in peritoneal cavities. Nevertheless, IFN suppressed the growth of not only S1 cells but also R1 cells in mice inoculated i.p. with these cells, and the survival rates of both S1 cell recipients and R1 cell recipients were markedly improved. S1 cells were observed microscopically to be injured by the direct effect of IFN in vitro and in vivo, but R1 cells in in vitro culture with IFN and those surviving in vivo in the presence of IFN appeared to proliferate well. In the peritoneal cavity of R1 recipients treated daily with IFN, the recruitment of macrophages was enhanced in comparison with untreated R1 recipients. Adherent peritoneal exudate cells obtained from IFN-treated, R1 bearing mice were highly suppressive for the in vitro growth of not only R1 cells but also allogeneic and human cells. The role of macrophages in the indirect effect of IFN on tumor cell growth is discussed. PMID- 2578879 TI - Potentiation of cell killing by inhibitors of poly(adenosine diphosphate-ribose) synthesis in bleomycin-treated Chinese hamster ovary cells. AB - Bleomycin-treated Chinese hamster ovary cells synthesize poly(adenosine diphosphate-ribose) in a reaction which is dose and time dependent. Treatment with two poly(adenosine diphosphate-ribose) synthesis inhibitors (3 aminobenzamide and 3-methoxybenzamide) slows down the restoration of DNA structure in bleomycin-treated cells, as shown by nucleoid sedimentation. When added in the culture medium, these inhibitors increase the cell sensitivity towards bleomycin, in the case of both exponentially growing and stationary cells. In control experiments, plateau-phase cells treated with bleomycin can recover by repairing efficiently the potentially lethal damage; this type of repair is mostly suppressed in the presence of the poly(adenosine diphosphate ribose) synthesis inhibitors. PMID- 2578881 TI - Basal-cell subpopulations and cell-cycle kinetics in human epidermal explant cultures. AB - Cultured human epidermal cells were studied by cell sorting and autoradiography after different 3H-thymidine (3H-dThd)-labelling procedures and after labelling with DNA precursors that are incorporated via salvage or de novo pathways. It was shown that 3H-dThd incorporation was the best measure of the rate of DNA replication. Dose-response experiments with pulse and continuous labelling revealed that all S- and G2-phase cells were cycling, whereas some 20% of the cells stayed in G1-phase for long periods of time. Most, if not all of these cells were probably non-proliferating differentiated keratinocytes. At least two subpopulations of S-phase cells could be discriminated on the basis of the rate of incorporation of DNA precursors. The difference in precursor incorporation did not seem to be caused by differences in nucleotide metabolism but rather to reflect true differences in the rate of DNA replication. Continuous labelling experiments showed that these subpopulations also were apparent in the G1- and G2 phases. Studies of the grain-count distribution revealed that cells that appeared to move rapidly through the S-phase moved slowly through the G2-phase, and vice versa. Cells stained with acridine orange were subjected to a two-parameter analysis in the cell sorter by simultaneous measurement of the DNA and RNA fluorescence. Autoradiography of sorted cells revealed that, on average, cells with low RNA contents incorporated 3H-dThd at a higher rate than cells with high RNA contents. PMID- 2578880 TI - Phase II trial of cyclophosphamide, doxorubicin, and cisplatin (CAP) versus amsacrine in patients with transitional cell carcinoma of the urinary bladder: a Southwest Oncology Group study. AB - The combination of cyclophosphamide, doxorubicin, and cisplatin (CAP) was reported to be effective in patients with metastatic transitional cell cancer of the urinary bladder. This study was designed to test the effectiveness of the phase II agent amsacrine (m-AMSA) versus CAP in patients previously untreated with systemic chemotherapy, with crossover if no response occurred or at the time of progression. In 23 patients who were randomized to receive CAP, three achieved complete response, seven achieved partial response, six had stable disease, and seven had disease progression. The responses in the 22 patients who received m AMSA were: one with complete response, three with partial response, six with stable disease, and 12 with progressive disease. The overall response rate to initial CAP therapy was 43% compared to 19% for initial m-AMSA therapy. The median duration of response to CAP was 28 weeks and to m-AMSA was 21 weeks. There were no statistically significant differences in the durations of response or survival times between the groups. The main side effects of CAP were: nausea and/or vomiting, leukopenia, anemia, thrombocytopenia, and renal toxicity. Leukopenia and anemia were the major toxic effects of m-AMSA. Our study supports the justification for testing phase II agent(s) in previously untreated patients with bladder cancer with systemic chemotherapy, provided adequate crossover to a known active single or combination of agents is built into the design of such a trial. PMID- 2578882 TI - Molecular organization of the AIDS retrovirus. PMID- 2578883 TI - Retroviruses and retrotransposons: the role of reverse transcription in shaping the eukaryotic genome. PMID- 2578884 TI - Altering gene expression with 5-azacytidine. PMID- 2578885 TI - Isolation and sequence of a cDNA encoding the major structural protein of peripheral myelin. AB - The myelin sheath is a multilayered membrane, unique to the nervous system, which functions as an insulator to increase greatly the velocity of axonal impulse conduction. We have used the techniques of differential screening and hybrid selection to identify a cDNA clone encoding the Schwann cell glycoprotein P0, the major structural protein of the peripheral myelin sheath. The sequence of this protein, deduced from the nucleotide sequence of the cloned cDNA, indicates that P0 is an integral membrane protein containing a single membrane-spanning region, a large hydrophobic extracellular domain, and a smaller basic intracellular domain. The structure of the protein suggests that each of these domains plays an essential role in generating the highly ordered structure of the myelin sheath. Furthermore, we find that the induction of P0 mRNA coincides with the initiation of myelin formation, and we propose a model in which the glycoprotein serves as a molecular guidepost for this process. PMID- 2578886 TI - Control of ColE1 plasmid replication: initial interaction of RNA I and the primer transcript is reversible. AB - Replication of ColE1-type plasmids is known to be regulated by a plasmid-specific RNA (RNA I), whose binding to the transcript (RNA II) from the primer promoter results in inhibition of formation of the primer for DNA replication. In this paper, it is shown that binding of RNA I to the homologous RNA II is inhibited by an RNA I specified by a plasmid of different compatibility. The inhibition is caused by the reversible interaction of RNA II with the heterologous RNA I, which competes with reversible interaction of the two homologous RNAs at a step preceding their stable binding. As predicted from these results, the copy numbers of both ColE1 and RSF1030 are increased when both plasmids are present in the same cell. The Rom protein enhances the reversible interaction. PMID- 2578887 TI - Organelle, bead, and microtubule translocations promoted by soluble factors from the squid giant axon. AB - A reconstituted system for examining directed organelle movements along purified microtubules has been developed. Axoplasm from the squid giant axon was separated into soluble supernatant and organelle-enriched fractions. Movement of axoplasmic organelles along MAP-free microtubules occurred consistently only after addition of axoplasmic supernatant and ATP. The velocity of such organelle movement (1.6 micron/sec) was the same as in dissociated axoplasm. The axoplasmic supernatant also supported movement of microtubules along a glass surface and movement of carboxylated latex beads along microtubules at 0.5 micron/sec. The direction of microtubule movement on glass was opposite to that of organelle and bead movement on microtubules. The factors supporting movements of microtubules, beads, and organelles were sensitive to heat, trypsin, AMP-PNP and 100 microM vanadate. All of these movements may be driven by a single, soluble ATPase that binds reversibly to organelles, beads, or glass and generates a translocating force on a microtubule. PMID- 2578888 TI - Stimulation of the T3-T cell receptor complex induces a membrane-potential sensitive calcium influx. AB - Three monoclonal antibodies selected for their recognition of parts of the T3-T cell receptor complex on human T lymphocytes were found to induce an increase in cytoplasmic free Ca2+ (Ca2+i) in the T cell leukemia line HPB-ALL as measured by Quin2 fluorescence. These reagents are directed against T3 (OKT3), a nonvariable T3-associated structure (WT-31) and the variable region of the T3-associated antigen receptor (T40/25) of this cell line. The rise in Ca2+i was dependent on the presence of extracellular Ca2+, occurred within 30 sec of stimulation, and was sustained for at least 10 min. Fab fragments of OKT3 also caused a rapid increase in Ca2+i, indicating that cross-linking is not necessary to induce a Ca2+ response. Alterations in plasma membrane potential and La3+ blocked the Ca2+ influx induced by OKT3 and T40/25. These data suggest that the T3-T cell receptor complex of human T lymphocytes may be an antigen-regulated Ca2+ channel. PMID- 2578889 TI - Requirement for metalloendoprotease in exocytosis: evidence in mast cells and adrenal chromaffin cells. AB - Exocytosis is initiated by the receptor-mediated influx of calcium that results in fusion of the secretory vesicle with the plasma membrane. We examined the possibility that calcium-dependent exocytosis in mast cells and adrenal chromaffin cells requires metalloendoprotease activity. Metalloendoprotease inhibitors and dipeptide substrates block exocytosis in these cells with the same specificity and dose dependency as that with which they interact with metalloendoproteases. Metalloendoprotease activity is identified in these cells with fluorogenic synthetic substrates, which also blocked exocytosis. Metalloendoprotease activity is highest in the plasma membrane of chromaffin cells. The metalloendoprotease appears to be required in exocytosis at a step dependent on or after calcium entry, since exocytosis initiated by direct calcium introduction in both mast cells and chromaffin cells is blocked by metalloendoprotease inhibitors. PMID- 2578890 TI - Enzymatic cross-linking of involucrin and other proteins by keratinocyte particulates in vitro. AB - A transglutaminase-catalyzed cross-linking process characteristic of keratinocytes leads to the formation of the insoluble corneocyte envelope. The essentials of this process take place in vitro in a reconstituted system derived from subcellular fractions. A particulate fraction containing membrane-bound envelope precursor proteins and the enzyme transglutaminase is combined with cytosolic proteins; when the enzyme is activated by Ca++, cytosolic proteins are removed from solution and cross-linked to particulate proteins. This interaction is cell-type-specific, since particulates derived from fibroblasts and also containing transglutaminase activity cannot substitute for those of keratinocytes. Involucrin, a cytosolic protein known to be a precursor of the envelope, is more efficiently cross-linked than other cytosolic proteins. The cross-linking of proteins of the particulate fraction (membrane proteins) is promoted by the presence of involucrin. PMID- 2578892 TI - Syngeneic sensitization of mouse lymphocytes on monolayers of thyroid epithelial cells. VII. Generation of thyroid-specific cytotoxic effector cells. AB - During primary syngeneic sensitization of lymphocytes on monolayers of thyroid epithelial cells (TEC), lymphoblasts are generated as assessed by thymidine uptake. When these thyroid-sensitized lymphoblasts are deposited onto 51Cr labeled TEC used as target cells, syngeneic cytotoxicity (SC) occurs after 5 hr. The effector cell of this SC is a T lymphocyte, belonging to the Lyt-2 T-cell subset. Moreover, blocking experiments demonstrated that SC involves class I major histocompatibility complex and thyroglobulin (Tg) antigens. These data demonstrate that SC can be compared to the classical hapten or virus self mediated cytotoxicity, but in this case Tg plays the role of these agents. The in vivo relevance of this SC is discussed. PMID- 2578891 TI - Keratinocyte-specific transglutaminase of cultured human epidermal cells: relation to cross-linked envelope formation and terminal differentiation. AB - The predominant form of the cross-linking enzyme, transglutaminase, in cultured normal human epidermal keratinocytes, is found in cell particulate material and can be solubilized by nonionic detergent. It elutes as a single peak upon either anion-exchange or gel-filtration chromatography. Monoclonal antibodies raised to the particulate enzyme cross-react with one of two transglutaminases in the cell cytosol. The second cytosolic transglutaminase, which has distinct kinetic and physical properties from the first, does not cross-react and is not essential for formation of the keratinocyte cross-linked envelope in vitro. The anti transglutaminase antibodies stain the more differentiated layers of epidermis in a pattern similar to that given by anti-involucrin antiserum. These observations support the hypothesis that the transglutaminase so identified is involved in cross-linked envelope formation in vivo. PMID- 2578893 TI - Antigen- and isotype-specific regulation of IgE responses by Lyt 1+,2,3- and Lyt 1-,2,3+ T suppressor cells. AB - Antigen-specific, IgE isotype-selective suppression is induced following treatment of mice with a high-molecular-weight glutaraldehyde-polymerized ovalbumin preparation (OA-POL). The results show that the suppression is mediated by Lyt 1+,2,3- cells residing in the spleen. Adoptive transfer experiments indicate that Lyt 2,3+ or Lyt 1,2,3+ cells are not required for the establishment of suppression by these Lyt 1+,2,3- suppressor T cells (Ts). Treatment of OA-POL induced Ts cells with anti-I-Jk serum and complement does not affect their ability to suppress. In marked contrast, spleen cells from animals treated with a single course of OA-POL almost 300 days previously, were shown to contain boosterable memory suppressor T cells (Tsm) which display the Lyt 1-,2,3+ phenotype. The activity of both Ts and Tsm cells appears to result from stimulation by determinants common to native OA and OA-POL rather than by idiotypic determinants expressed on anti-OA antibodies. PMID- 2578894 TI - Lymphocytes express a diverse array of specific receptors for sulfated polysaccharides. AB - Lymphocyte receptors for sulfated polysaccharides were detected in two ways, namely, by the ability of lymphocytes to form rosettes with sheep red blood cells (SRBC) coupled with one of fourteen different sulfated polysaccharides, and by the ability of cholate extracts of lymphocytes to hemagglutinate the same sulfated polysaccharide-coupled SRBC. It was found that murine lymphocytes lacked receptors for a number of glycosaminoglycans, such as hyaluronic acid, chondroitin-4-sulfate, chondroitin-6-sulfate, and dermatan sulfate, but reacted strongly with heparin, arteparon, and a number of sulfated polysaccharides of plant and bacterial origin. In each case receptor activity was demonstrated by rosetting and by the ability of lymphocyte lysates to strongly agglutinate sulfated polysaccharide-coupled SRBC. The receptors exhibited a high degree of diversity as evidenced by (a) only subpopulations of lymphocytes, particularly splenic B cells, expressing receptors for some of the sulfated polysaccharides and (b) hemagglutination-inhibition analyses revealing numerous subsets of receptors with different binding specificities. Receptor diversity was further highlighted by a 48% difference in the hemagglutination-inhibiton results between thymus and spleen. It is proposed that these receptors are involved in cell-cell communication and lymphocyte homing and recirculation. The likely target structures for the receptors in vivo are the heparan sulfates, a ubiquitous and structurally diverse family of sulfated glycosaminoglycans. PMID- 2578896 TI - Synergy of helper factors in the differentiation of in vivo-preactivated antigen specific human B cells. AB - After in vivo immunization with antigen, B cells appear in the peripheral blood which can be induced in vitro by nonspecific factors found in mixed lymphocyte culture supernatants (MLC-SN) to differentiate and secrete antibody specific for the immunizing antigen. In order to further delineate the nature of the factors involved in the differentiation of these in vivo-activated B cells, various helper factors, including interleukin 1 and interleukin 2 (IL-1 and IL-2), B-cell growth factor (BCGF), and B-cell differentiation factor (BCDF) were added separately and in combination to cultures of these preactivated B cells. T-cell depleted fractions of peripheral blood mononuclear cells were obtained from normal individuals immunized in vivo with keyhole limpet hemocyanin. MLC-SN alone, without the addition of antigen, selectively triggered an antibody response specific for the antigen used to immunize in vivo in the absence of a polyclonal B-cell response. In order to obtain responses equal to those seen with MLC-SN, a combination of BCGF, IL-2, and BCDF was required, although any two factors partially reconstituted the response. Exogenous IL-1 had the least effect but was suppressive in the presence of optimal concentrations of monocytes. Thus, for maximal in vitro differentiation of in vivo-preactivated B cells, a combination of at least three helper factors is required and acts in a synergistic manner to induce antigen-specific antibody responses. PMID- 2578895 TI - Acute experimental allergic encephalomyelitis in the mouse: immunopathology of the developing lesion. AB - To investigate the sequence of immunopathologic events during lesion formation in acute experimental allergic encephalomyelitis (EAE), SJL/J mice were inoculated with isogeneic spinal cord in complete Freund's adjuvant (CFA) and with Bordetella pertussis on Days 1 and 3 postinoculation (PI). Mice were sampled at different time points PI and T cells, T-cell subsets. Ia+ cells, Ig+ cells, albumin, and Ig deposits were localized in frozen sections by the avidin-biotin complex (ABC) method and direct fluorescence. Furthermore, samples were stained for Ia antigen, myelin basic protein (MBP), and galactocerebroside (GC) localization on endothelial cells by the ABC technique. Clinical and pathologic observations were correlated with the immunopathologic results. It was found that early in the disease process myelin and Ia-antigens were demonstrable on endothelial cells within the central nervous system (CNS). Simultaneously, damage to the blood-brain barrier was apparent, as indicated by albumin deposits, and small numbers of infiltrating T cells, T-cell subsets, and Ia+ cells were found. With time PI, the density of infiltrating total T cells (Thy-1.2+), helper/inducer (Lyt-1+), and suppressor/cytotoxic (Lyt-2+) T cells increased; Lyt 1+ and Lyt-2+ cells were detectable in meningeal as well as parenchymal infiltrates, while later on, Lyt-1+ cells showed some predilection for the CNS parenchyma and Lyt-2+ cells for meninges. Ia+ cells (B cells, macrophages, activated T cells) were present in small numbers only. Ig+ cells (B cells and macrophages) appeared shortly before onset of signs and persisted in moderate numbers. These results reconfirm the importance of early T-cell involvement for the development of EAE; they might also indicate a secondary role for Ig+ cells and are consistent with the concept that presentation of myelin antigens to T cells might occur locally on Ia-bearing endothelial cells within the CNS. PMID- 2578897 TI - Potent adjuvant action of lipopolysaccharides possessing the O-specific polysaccharide moieties consisting of mannans in antibody response against protein antigen. AB - It was previously reported that Klebsiella O3 lipopolysaccharide (LPS) exhibits extraordinarily strong adjuvant activity in augmenting antibody response against protein antigens in mice compared with other kinds of LPS, for example, LPS from Escherichia coli O55, O111, and O127 and Salmonella enteritidis. The present study was undertaken to clarify the relationship between the strong adjuvant activity in augmenting antibody response against deaggregated bovine gammaglobulin and the chemical structure of LPS. Among LPS from Klebsiella O1, O4, O5, and O7, only O5 LPS exhibited nearly the same degree of the strong adjuvant activity as did O3 LPS. The adjuvant activity of the other LPS was very weak in a degree similar to that of LPS from E. coli O55 and O127. Even when the natural forms of Klebsiella O3 LPS and O1 LPS were converted to various defined uniform salt forms, their adjuvant activity did not significantly differ from that of the respective natural forms. It is therefore unlikely that the difference in strength of the adjuvant activity between Klebsiella O3 LPS and O1 LPS is due to the difference in their salt forms. The common feature in the structures of Klebsiella O3 LPS and O5 LPS is their O-specific polysaccharide chains consisting of the mannose homopolysaccharides (mannans). LPS from E. coli O8 and O9, the O-specific polysaccharide chains of which consist of the mannans, also exhibited much stronger adjuvant activity than do LPS from E. coli O55 and O127, and the strength of the adjuvant activities of the former two was comparable to that of LPS from Klebsiella O3 and O5. On the other hand, LPS from Klebsiella O3 and O5 and E. coli O8 and O9 showed the ability to activate B lymphocytes polyclonally in vivo in a degree similar to that of the other kinds of LPS. From the present results it can be concluded that LPS possessing the O specific polysaccharide moieties consisting of the mannans exhibit extraordinarily strong adjuvant activity in augmenting antibody response against protein antigen. PMID- 2578900 TI - Sodium pump inhibition, enhanced calcium influx via sodium-calcium exchange, and positive inotropic response in cultured heart cells. AB - The effects of sodium pump inhibition produced by exposure to the cardiac glycosides, ouabain or dihydroouabain, or by reduction in extracellular potassium to 1.0 mM, on contractile state and sodium-calcium exchange were studied in primary monolayer cultures of chick embryo ventricular cells. Ouabain, 10(-6)M, dihydroouabain, 5 X 10(-5)M, and extracellular potassium of 1.0 mM all induced similar and prominent positive inotropic effects. These effects were accompanied, in each case, by 40-50% inhibition of the rate of active uptake of 42K and by similar increases in steady state sodium content. Stimulation of the rate of 45Ca uptake on exposure to zero extracellular sodium occurred in response to extracellular potassium (1.0 mM) or to glycoside concentrations that induced a positive inotropic effect and sodium-potassium pump inhibition. Reactivation of the sodium pump after return from 1.0 to 4.0 mM extracellular potassium was rapid and was associated with membrane hyperpolarization and slowing of spontaneous beating rate. With pump reactivation under these circumstances, the time course of disappearance of stimulation of sodium-calcium exchange on exposure to zero extracellular sodium was similar to the time course of loss of the positive inotropic effect. Under physiological conditions (4.0 mM extracellular potassium), exposure to positively inotropic but nontoxic concentrations of ouabain or dihydroouabain caused a small but consistent increase in unidirectional calcium influx, but had no discernible effect on calcium efflux. Since similar inotropic effects were produced for comparable degrees of glycoside or low extracellular potassium-induced sodium pump inhibition and increases in cellular sodium content, sodium pump inhibition rather than a glycoside-specific change in calcium binding appears to underlie the inotropic response. These findings are further consistent with the view that the primary mechanism of the positive inotropic effects of digitalis and low extracellular potassium in this experimental preparation is sodium pump inhibition resulting in increased intracellular sodium. We suggest that increased calcium influx via sodium-calcium exchange is the principal mechanism whereby increased intracellular sodium results in enhanced calcium availability to the myofibrils, but an additional effect on calcium efflux is not excluded. PMID- 2578901 TI - Postextrasystolic potentiation of the isolated canine left ventricle. Relationship to mechanical restitution. AB - We established, for the isolated, isovolumically beating canine left ventricle, a comprehensive description of postextrasystolic contractile strength (dP/dtmax) as a function of extrasystolic and postextrasystolic stimulus intervals. In contrast to previous studies of postextrasystolic beats in in situ hearts, these isolated ventricles contracted isovolumically so that dP/dtmax was not affected by fluctuations in preload and afterload and was therefore considered to be a reliable index of intrinsic contractility. With the interval preceding extrasystoles constant, postextrasystolic contractile strength increased monoexponentially to a plateau as the interval preceding postextrasystoles lengthened, with a mean time constant (+/- SD) of 182 +/- 44 msec (n = 53). The onset of this increase in postextrasystolic contractile strength coincided with repolarization of the extrasystolic action potential. With the interval preceding postextrasystoles held constant and long (1200 msec), postextrasystolic contractile strength decreased according to a monoexponential function as the interval preceding extrasystoles lengthened [mean time constant (+/- SD) of 176 +/- 18 msec (n = 10)]. These phenomena could be quantitatively summarized by a single equation description of postextrasystolic contractile strength which involved monoexponential functions with one time constant. The mathematical form of this description led us to a simple interpretation of these phenomena in terms of currently proposed excitation-contraction coupling models of the heart. PMID- 2578898 TI - Changes in pulmonary function during and after bleomycin treatment in patients with testicular carcinoma. AB - Pulmonary function tests, including spirometry, transfer factor of the lungs for carbon monoxide (TlCO), and the two components of TlCO, the diffusing capacity of the alveolocapillary membrane (Dm) and pulmonary capillary blood volume (Vc), were carried out in a group of patients with testicular carcinoma during and after treatment with the Einhorn regimen. The lung function parameters of patients who developed bleomycin-induced pneumonitis were compared with those recorded in a group of patients who did not develop this syndrome. We suggest that bleomycin-induced damage to the pulmonary capillary vasculature can be monitored by measuring Vc and that ensuing fibrosis can be measured by recording Dm. The decrease in Dm is probably compensated for by an increase in Vc, leading to a smaller change in TlCO. PMID- 2578899 TI - Development of phorbol ester responsiveness in neonatal mouse epidermis: correlation between hyperplastic response and sensitivity to first-stage tumor promotion. AB - As compared with the adult state, neonatal mouse skin (strain NMRI) has a hyperplastic appearance which gradually changes into the mature type between postnatal day 3 and 10. Concomitantly, the late fetal and neonatal keratin polypeptide pattern is replaced by the mature pattern. As long as the adult type of epidermal differentiation is not sufficiently developed (i.e., prior to postnatal day 5), topical application of the phorbol ester tumor promoter 12-O tetradecanoyl-phorbol-13-acetate (TPA) causes neither morphological alterations nor a measurable induction of cellular proliferation and ornithine decarboxylase activity. TPA application at day 7 evokes, however, (i) a hyperplastic reaction followed by a massive 'psoriasis-like' hyperkeratosis, (ii) an increase of ornithine decarboxylase activity and (iii) a restoration of the neonatal keratin polypeptide pattern. Multistage tumorigenesis experiments carried out with prenatally initiated mice show that during the early period of development (prior to postnatal day 5) mouse skin is also resistant to the effects of TPA as a stage I tumor promoter. Since both the hyperplastic response and the sensitivity to tumor promotion develops in a strictly parallel manner, reactions involved in the induction of epidermal hyperplasia are assumed to provide an important condition of stage I skin tumor promotion. PMID- 2578902 TI - Contribution of left ventricular contraction to the generation of right ventricular systolic pressure in the human heart. AB - To determine whether left ventricular (LV) contraction contributes to the generation of right ventricular (RV) systolic pressure in humans, LV and RV pressures and their first derivative (dP/dt) were recorded simultaneously with micromanometer-tipped catheters in 11 conscious subjects. Seven subjects had normal LV and coronary angiograms. Four subjects had moderate LV dysfunction (resting ejection fraction 0.40 to 0.50), and three of these had coronary artery disease. During normal sinus rhythm, LV contraction slightly preceded RV contraction (mean 20 msec), and LV and RV dP/dt recordings showed single positive systolic peaks that were coincident. During endocardial pacing of the RV free wall, RV contraction preceded LV contraction (mean 23 msec) and two systolic RV dP/dt peaks were recorded, the first (peak I) occurring significantly before (mean +/- SD = 67 +/- 23 msec, p less than .01), and the second (peak II) coincident with the single systolic LV dP/dt peak. RV ectopic beats produced a similar RV dP/dt pattern, with peak I occurring 63 +/- 11 msec (p less than .01) before, and peak II coincident with the single LV dP/dt peak. Conversely, during LV ectopic beats, LV contraction preceded RV contraction (mean 63 msec) and two systolic RV dP/dt peaks were recorded, but peak I was coincident with the single LV dP/dt peak, while peak II occurred significantly later (63 +/- 26 msec, p less than .01). In two subjects right bundle branch block produced similar findings. In three subjects left bundle branch block produced little ventricular asynchrony (mean 14 msec), but did delay the development of peak LV dP/dt after LV contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2578903 TI - Early loss of postextrasystolic potentiation in acutely ischemic myocardium: evaluation by contrast two-dimensional echocardiography. AB - Studies in animals with acutely ischemic hearts have suggested that postextrasystolic potentiation (PESP) may predict the viability of dysfunctional myocardium. Most of these data have been obtained with sonomicrometers and therefore the presence and extent of PESP throughout the entire region at risk has not been defined. In this study we used contrast two-dimensional echocardiography (2DE) to define region at risk in vivo, and then with quantitative 2DE we examined the proportion of the region at risk that demonstrated PESP, the degree of the potentiation, and the time course of this response. The region at risk was divided into a central (inner 50%) and two peripheral (25% each) ischemic zones. Adjacent contrast-enhanced myocardium was divided into near and far border zones that were equal in size to the adjacent peripheral ischemic zone. Systolic thickening was analyzed within each zone along multiple radii at 5, 30, and 120 min after coronary occlusion. PESP was absent in the central ischemic zone at all three times. In the peripheral ischemic zone at 5 min, a small amount of PESP was detected (-4.1% vs + 3.1% for nonpotentiated and potentiated thickening, respectively; p less than .01). At 30 min after occlusion, no potentiation was seen in the region at risk and PESP was confined to the contrast-enhanced near and far border zones. These findings persisted at 120 min. These data indicate that the response to PESP is localized to perfused myocardium by 30 min after acute occlusion. PESP is therefore of limited value in predicting the presence of ischemic, potentially viable myocardium early in the course of acute infarction. PMID- 2578904 TI - The effects of single premature stimuli on automatic and triggered rhythms in isolated canine Purkinje fibers. AB - We studied the effects of single premature stimuli on automatic and triggered rhythms occurring in preparations of isolated canine Purkinje fibers. Preparations were made from false tendons, the subendocardial right bundle branch, and infarct zone Purkinje fibers 24 hr after occlusion of the left anterior descending coronary artery, and were studied by standard microelectrode techniques. Single premature impulses almost always produced reset of automatic rhythms, whether the pacemaker had a low (less than -60 mV), intermediate (-61 to -70 mV), or high (greater than -70 mV) maximum diastolic potential. In contrast, single premature impulses imposed on triggered rhythms sometimes were found to alter these rhythms; often, early premature impulses (i.e., during phase 3) resulted in either a shortened first return cycle or a short period of arrest of the rhythm. The results of this study indicate that it may be possible to design simple electrophysiologic tests using single premature stimuli to determine whether an arrhythmia is being caused by an automatic focus or by triggered activity. PMID- 2578905 TI - A retrospective look at studies on prostate-specific antigen. PMID- 2578907 TI - Interpretation of the specificities of monoclonal antibodies recognising human MHC class II antigens. PMID- 2578906 TI - MRL/Mp-lpr/lpr mouse derived monoclonal antibodies that recognise determinants shared by poly (ADP-ribose), single stranded DNA and left handed Z-DNA. AB - MRL/Mp-lpr/lpr (MRL/l) mice spontaneously produce antibodies to poly(ADP-ribose) that are cross-reactive with single stranded DNA (ssDNA). Spleen cells from these animals were used for fusion with murine plasmacytoma cells to prepare hybridomas that produce autoantibodies to poly(ADP-ribose). Monoclonal antibodies (MoAb) produced by the selected hybridomas not only preferred ssDNA to poly(ADP-ribose), but also reacted with left handed Z-DNA; the MoAb reflected the nature of serum antibodies to poly (ADP-ribose) in MRL/l mice. These results suggest that similar antigenic determinants exist in poly (ADP-ribose), ssDNA and left handed Z-DNA and that the cross-reactive nature of autoantibodies to poly (ADP-ribose) in MRL/l mice may be the results of expansion of such clones as selected in this experiment. PMID- 2578908 TI - T-cell subsets in the hyporesponsiveness to hepatitis B surface antigen (HBsAg) and antigen-specific suppressor lymphocytes in chronic hepatitis B virus (HBV) infection. AB - In contrast to convalescent hepatitis B patients, who exhibit the ability to elicit a specific immune response to HBsAg, patients with chronic hepatitis B virus (HBV) infection are markedly hyporesponsive to HBsAg and show a decrease in the normal ratio of OKT4-positive (helper/inducer) to OKT8-positive (suppressor/cytotoxic) lymphocytes. In this study the role of OKT4-positive and OKT8-positive cells on cellular immune response to HBsAg was evaluated in patients with chronic HBV infection and the ability of such patients to develop antigen-specific suppressor lymphocytes after in vitro sensitization to HBsAg. Elimination of OKT8-positive cells markedly improved the in vitro lymphocyte proliferative response to HBsAg without altering the reactivity of cells from the same donor to PPD or Candida. In contrast, the degree of responsiveness to HBsAg was not affected by the depletion of OKT4-positive cells. In vitro co-culture experiments, performed in the seven chronically HBV-infected patients who showed a proliferative response when their PBM were cultured with purified HBsAg or PPD, have demonstrated that lymphocytes from chronic HBV carriers, stimulated with HBsAg, inhibit the response of autologous PBM to HBsAg but not to the unrelated antigen PPD. PMID- 2578909 TI - The effect of bacterial lipopolysaccharide (LPS) on histamine release from human basophils. I. Enhancement of immunologic release by LPS. AB - Preincubation of human basophils with bacterial lipopolysaccharide (LPS) purified from the heptose-deficient mutant Salmonella minnesota R595 enhanced by an average of sixfold the response of peripheral blood basophils obtained from allergic donors to several allergens in vitro as judged by release of histamine. Enhancement occurred at suboptimal, optimal, and supraoptimal concentrations of antigen. No effect was seen if basophils were from a nonallergic donor, and LPS by itself rarely caused histamine release from any preparation of basophils. However, histamine release in basophils from nonallergic donors induced by antibody directed against IgE (anti-IgE) also was enhanced by LPS. Potentiation of histamine release occurred if basophils were pretreated with LPS before addition of anti-IgE for as little as 5 min; there was no increase in release if anti-IgE and LPS were added simultaneously to cells. LPS enhanced the rate of release without altering duration of the release response. LPS potentiation of release of histamine by F(ab')2 fragments of anti-IgE was equivalent to its effect on release triggered by the intact antibody molecule, confirming that the effect of LPS is not due solely to its interaction with the Fc component of the anti-IgE. These data thus provide evidence for modulation of basophil response to IgE-mediated stimuli by LPS, resulting in a significant enhancement of response. Enhancement by LPS appears to be independent of the stimulus which triggers the IgE receptor. The contribution of this mechanism to allergic disease or asthma remains to be determined. PMID- 2578910 TI - Expression of a highly conserved anti-DNA idiotype in normal and autoimmune mice. AB - The specificity and idiotypic relationships of a monoclonal anti-DNA antibody were investigated to evaluate genetic control in this autoantibody response. 6/0 is an IgG2a monoclonal anti-DNA derived by the fusion of spleen cells from an autoimmune MRL-lpr/lpr mouse and the cell line NS1. By an enzyme-linked immunosorbent assay (ELISA) for anti-DNA, 6/0 demonstrated preference for single stranded DNA and bound deoxyribo- and ribohomopolymers of dissimilar base composition. The control of 6/0 expression was evaluated by idiotypic analysis using a rabbit anti-6/0 antiserum made specific by absorption with the BALB/c myelomas UPC 10 (IgG2a) and MOPC 21 (IgG1). The resulting preparation was fractionated by BALB/c IgG affinity columns to provide antibodies to idiotypic determinants essentially unique to 6/0 and those commonly expressed in sera. The commonly expressed 6/0 idiotype was found in sera of ten inbred strains of mice and was not exclusive to the autoimmune strains. MRL-lpr/lpr and A/J strain mice displayed idiotype levels almost fivefold greater than other strains, with 6/0 idiotype-bearing antibodies having serum concentrations as high as 1 mg/ml. Levels of the 6/0 idiotype, however, did not correlate with anti-DNA levels among the various strains. In addition to mice, the majority of individuals of three inbred rat strains showed detectable 6/0 idiotype in their sera. These results suggest that the 6/0 idiotype, although identified using a monoclonal anti-DNA antibody, represents a framework determinant that is phylogenetically conserved. The mechanisms for the expression of this determinant may differ among the normal and autoimmune strains. PMID- 2578911 TI - Inappropriate uses of stimulant medications. AB - The utility of stimulant medications in the treatment of attention deficit disorder (ADD) has been demonstrated repeatedly. Over 500,000 children receive these medications in the United States each year. The drugs, however, may be used inappropriately in cases where a presumptive diagnosis of "hyperactivity" is mistakenly made on the basis of nonspecific increases in activity levels or when an initial sedative response is taken as diagnostic confirmation of ADD. In this series of six cases, stimulant medications had been used inappropriately to manage a range of developmental problems. The importance of a careful diagnostic evaluation before instituting stimulants, careful monitoring, and a consideration of their risks are emphasized. PMID- 2578912 TI - Effects of amitriptyline and imipramine on brain amine neurotransmitter metabolites in cerebrospinal fluid. AB - The effects of amitriptyline (AMI) or imipramine (IMI) on levels of 3-methoxy-4 hydroxyphenylethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) (the major brain metabolites of the neurotransmitters norepinephrine [NE], serotonin [5-HT], and dopamine [DA]) in cerebrospinal fluid were determined in 66 subjects with unipolar and bipolar depression. There were significant reductions in MHPG and 5-HIAA levels for the depressed group taken as a whole, but levels of HVA did not change significantly. The changes were similar when subjects were grouped as treated with AMI and IMI and with unipolar and bipolar depression. Reductions in MHPG and 5-HIAA levels were greater in women than in men. In all subjects with depression and in those treated with AMI and IMI, amine metabolite changes did not differ significantly between those who had a positive clinical response to drug therapy and those who did not. Responders with bipolar depression had smaller reductions in MHPG levels than did responders with unipolar depression. The similar effects of AMI and IMI on MHPG and 5-HIAA differ from the dissimilar effects of the two drugs on NE and 5-HT amine uptake systems reported in animal and in in vitro studies. Results provide conclusive evidence of the effects of AMI and IMI on noradrenergic and serotonergic (but not dopaminergic) systems in patients with depression. PMID- 2578913 TI - Sodium pentosan polysulphate as a polyanionic inhibitor of calcium oxalate crystallization in vitro and in vivo. AB - Studies in vitro showed that sodium pentosan polysulphate (SPP) is an active inhibitor of calcium oxalate crystal growth and agglomeration and that it acts by increasing the negative zeta potential on the surface of calcium oxalate crystals. Oral administration to human subjects resulted in an increase in the negative zeta potential, which is consistent with an increase in the polyanionic inhibitory activity of urine. SPP may offer a novel approach to the medical management of recurrent calcium oxalate stone disease. PMID- 2578914 TI - Human mast cells recovered by bronchoalveolar lavage: their morphology, histamine release and the effects of sodium cromoglycate. AB - Mast cells make up between 0.5 and 3% (mean 1.35%) of total cells recovered by bronchoalveolar lavage (BAL). The majority of these cells have the morphological characteristics of mucosal mast cells in that they fail to stain in the alcian blue-safranin reaction after fixation in formol-saline but stain well after fixation in Carnoy's solution. Cells staining with berberine sulphate were seen in only four of the 26 lavages. BAL cells released histamine in response to anti human immunoglobulin E (IgE) in a dose-dependent manner that was optimal at a dilution of anti-IgE of 1:100. Maximum release was obtained by 2 min. Histamine release was completely inhibited by a combination of 2-deoxyglucose (5 mmol/l) and antimycin A (1 mumol/l). Disodium cromoglycate (DSCG) significantly inhibited this histamine release at 1 mmol/l (P less than 0.02), 100 mumol/l (P less than 0.002) and 10 mumol/l (P less than 0.003), with maximum inhibition of 50.1% at 10 mumol/l. PMID- 2578915 TI - Low-molecular-weight iron complexes and oxygen radical reactions in idiopathic haemochromatosis. AB - The sera of patients with idiopathic haemochromatosis and iron-overload have been found to contain low-molecular-weight iron complexes detectable in the 'bleomycin assay'. These complexes stimulate both the peroxidation of membrane lipids and the formation of the highly reactive and damaging hydroxyl radical. The iron chelator desferrioxamine interferes with these reactions. We suggest that oxygen radical reactions stimulated by iron salts are important in the pathology of idiopathic haemochromatosis. PMID- 2578916 TI - Role of endothelium in the contractile response of rat aorta to alpha adrenoceptor agonists. AB - The influence of endothelium on the response of rat isolated aorta to alpha adrenergic agonists has been studied by comparing the response of intact and denuded preparations before and after treatment with calcium entry blockers flunarizine and nifedipine. Endothelium removal enhanced the response of the preparations, especially to alpha 2-agonists that had a weak effect in intact preparations. In the absence of endothelium, about 80% of the maximum response to clonidine was blocked by calcium entry blockers, whereas only 25% of the maximum response to noradrenaline was sensitive to them. In contrast about 40% of maximum noradrenaline-evoked contractions was sensitive to calcium entry blockers in the presence of endothelium. This may be attributed to an increase in the intracellular exchangeable calcium fraction, likely to be due to a slight depolarization of smooth muscle membrane of denuded preparations, which are highly sensitive to the calcium agonist BAY K 8644. The results indicate that a factor liberated by endothelial cells controls both calcium entry and calcium release evoked by alpha-adrenoceptor agonists in vascular smooth muscle. PMID- 2578917 TI - Nursing care study: as normal a life as possible. PMID- 2578918 TI - Endomyocardial biopsy. PMID- 2578919 TI - Application of morphometric methods to study diffuse and focal injury in the lung caused by toxic agents. AB - Morphometric techniques are now being widely applied to a variety of toxicologic problems in order to obtain reproducible and quantitative data about changes in lung structure caused by environmental pollutants. Many environmental pollutants cause lung injury which is concentrated in specific regions of the lung, such as, in small airways and in the proximal portions of alveolar ducts. Morphometric techniques to obtain unbiased estimates of tissue changes occurring in these specific regions are reviewed and contrasted to well-established techniques for morphometric analysis of the distal alveolar regions of the lung. Specific applications of morphometric studies in different toxicologic problems are illustrated and include quantification of the changes in lung tissue and in lung cellular population pattern in response to exposure of small animals to hyperoxic atmospheres and to ozone. Pulmonary oxygen toxicity is an example of a diffuse lesion throughout the distal portion of the acinus whereas ozone exposure is an example of an environmental pollutant causing a greater degree of lung injury in the proximal alveolar region and in the small airways. PMID- 2578921 TI - Giardiasis as a chronic disease. AB - In an effort to better describe the incidence and characteristics of chronic giardiasis in an urban private practice outpatient setting, we reviewed our experience of 65 cases. In the entire group, the mean duration of symptoms was 1.9 years. A history of foreign travel was described by 45%. No association with homosexuality was noted. Chronic giardiasis, defined as that population symptomatic for six months or longer, constituted 58% of the entire group (38 cases). For these patients the mean duration of symptoms was 3.3 years. When compared to acute giardiasis, an increased frequency of constipation and upper gastrointestinal complaints was noted in the chronic population. Symptomatic cure was obtained in 71% of chronic cases and 93% of acute. Palliative results were noted in 18% of chronic cases and 4% of acute. We conclude that giardiasis is frequently a chronic disease in our population with symptoms lasting years. The incidence is similar in both sexes and a history of foreign travel is often absent. A disproportionate incidence in male homosexuals was not noted in our study. PMID- 2578920 TI - Lack of adaptive changes in human pancreatic amylase and lipase secretion in response to high-carbohydrate, low-fat diet applied by a 10-day continuous intraduodenal infusion. AB - In order to investigate whether the human exocrine pancreas is capable of adapting to a diet with a high-carbohydrate, low-fat, and normal protein content, 10 healthy subjects were given a continuous intraduodenal infusion of such a dietary composition (8760 kJ in 2400 ml/day) via a portable infusion pump over a period of 10 days. The diet consisted of 76% of calories as carbohydrates (80% oligosaccharides, 20% mono- and disaccharides), 10% as fat (more than 90% C18 fatty acids) and 14% as protein (oligo- and polypeptides; 11.8 g nitrogen per day). A complete pancreozymin-secretin test was carried out before and after the experimental period. The results show that the above dietary regimen leads to a significant (P less than 0.05) increase in the stimulated secretion rates of trypsin and chymotrypsin, whereas, in contrast to the findings in animal experiments, no change could be measured in the secretion rates of amylase and lipase. PMID- 2578922 TI - Effect of endorphins on amylase secretion from rat pancreas in vivo and in vitro. AB - The present study was done both in vivo by cannulating pancreatic duct of rats and in vitro using pancreatic slices and dissociated acini to determine the mode of action of endogenous opiate peptides on pancreatic acinar cell. Pancreatic slices were incubated with beta-endorphin or (Met)5-enkephalin alone and in combination with CCK8. Dissociated acini were incubated with naloxone, substance P, VIP, (Met)5- and (Leu)5-enkephalin and alpha-, beta-, and gamma-endorphin alone or in combination with CCK8. In vivo, both beta-endorphin and (Met)5 enkephalin did not alter basal secretion but inhibited CCK8-stimulated amylase secretion. This effect was not reversed by administration of naloxone. In the slices, neither beta-endorphin nor (Met)5-enkephalin altered basal or CCK8 stimulated secretion. In the dissociated acini, substance P and VIP significantly increased amylase secretion, whereas naloxone, enkephalins, and endorphins failed to alter amylase secretion. CCK8 increased amylase secretion greater than sixfold. In combination with enkephalins and endorphins, there was neither inhibition nor potentiation of CCK8 effect. These data indicate that the effect of opiate peptides on pancreatic acinar cells in the rat are nonspecific and appear not to be mediated by opiate receptors. PMID- 2578923 TI - Exocrine pancreatic function in rats after acute trypsin inhibitor treatment. AB - A single oral dose of synthetic trypsin inhibitor (TI, 20 mg/100 g) was given to rats by orogastric tube 6, 12, 18, or 24 hr before the removal of the pancreas and the preparation of isolated perfused pancreas. TI treatment induced no significant changes in body weight and total amount of DNA content in the pancreas, but pancreatic wet weight, total pancreatic protein and amylase, and the concentration of total protein and amylase relative to DNA were significantly decreased at 6 or 12 hr posttreatment, with a partial return toward control values at 18-24 hr after TI treatment. In isolated perfused pancreas, basal amylase output was similar in the control and in all 4 groups of TI-pretreated rats, while basal rate of flow of pancreatic juice was significantly increased at 12-24 hr posttreatment. Caerulein (0.1 ng/ml; 64 pM) stimulated pancreatic juice flow was greatly increased in rats pretreated with TI 12-24 hr earlier. In contrast, caerulein-stimulated amylase output was significantly lower in TI pretreated groups compared with the control. However, when amylase output was related to the total content in the pancreas, the secretory responsiveness for amylase release was significantly higher in rats at 6-18 hr posttreatment compared with the control. The present study indicates that a single oral administration of TI modulates biological response to caerulein in the isolated perfused pancreas. The enhanced responsiveness of amylase release to subsequent stimulation is seen in early periods, while that of pancreatic juice flow is observed in late periods. PMID- 2578924 TI - [Pancreatic secretion in domestic sprue]. AB - Pancreatic function was determined (using the secretin-pancreozymin test) before the use of gluten-free diet in 22 patients with endemic (celiac) sprue. Water and bicarbonate secretion were within normal limits, if anything there was a trend to high-normal values. Remarkable and apparently characteristic for celiac sprue was the only slight contraction of the gallbladder after intravenous injection of submaximal doses of cholecystokinin-pancreozymin (CCK). Secretion of the 3 enzymes amylase, lipase and trypsin was decreased in about one third of cases, the difference relating both to the concentrations and the amount secreted, compared with normal control values was significant (P greater than 0.01). But in no case was the reduced enzyme secretion so marked that one would expect maldigestion. Multivariate non-linear discriminance analysis demonstrated that pancreatic secretion in sprue is quite distinct from that in healthy subjects and those with chronic pancreatitis. It is assumed that there is a pattern of exocrine pancreatic secretion typical for sprue. PMID- 2578925 TI - [Morphological study of dog spermatozoa]. PMID- 2578927 TI - Short-latency scalp somatosensory evoked potentials and central spine to scalp propagation characteristics during peroneal and median nerve stimulation in multiple sclerosis. AB - Peripheral (cauda-lumbar, wrist-Erb, Erb-cervical) and central (cauda-vertex, cervical-scalp) nervous impulse propagation velocities and times to peroneal and median nerve stimulation were investigated in 34 patients suffering from definite (17 cases), probable (6 cases) and possible (11 cases) forms of multiple sclerosis (MS). In 6 cases short- and intermediate-latency scalp somatosensory evoked potentials to peroneal nerve stimulation were recorded with 'open' (1-5000 Hz, -6 dB) bandpass filters and subsequently digitally filtered through a 'narrow' bandpass (200-5000 Hz, -6 dB). The lumbar response was abnormal in 2.95% of legs, while the Erb response was always within normal limits. The cauda-vertex conduction was altered in 75% of the examined limbs (86.2% definite, 58.3% probable, 63.6% possible MS). Absent scalp responses to peroneal stimulation were often encountered during narrow bandpass recording (54.9%), while a slowed central conduction was less frequent (33.3%). Scalp responses when recorded with open bandpass were always identifiable, being delayed in 3 out of 6 cases. In 5 of these the short-latency wavelets were either absent or showed a prolonged interpeak time even when open filter records were normal. Median nerve SEPs were altered in 60.3% of cases, more frequently because of a delayed scalp response or of a prolonged cervical-scalp conduction time than because of an absent cervical or scalp response. When peroneal and median nerve data were considered together, the rate of abnormality rose to 88.2% of patients. Due to their length, afferent pathways from the lower limb might suffer from a loss of high frequency impulse coding as an early sign of defective impulse propagation. PMID- 2578926 TI - Prognostic value of the electroencephalogram in term and preterm infants following neonatal seizures. AB - There is controversy in the literature regarding the prognostic value of the EEG following neonatal seizures. This report reviews the results of a prospective study comparing EEG findings and outcome in 74 term and preterm infants following neonatal seizures. EEGs were evaluated for both background rhythms and epileptiform activity. Outcome was evaluated at an average age of 33 months. Background rhythms were highly correlated with outcome. Low voltage, electrocerebral inactivity and burst suppression EEGs were associated with poor outcomes while normal EEGs were associated with favorable outcomes. Slow, maturationally delayed and asymmetrical EEGs were associated with variable outcomes. The presence of epileptiform activity on the EEG was correlated with adverse outcomes but was not as highly significant as background rhythms. Electroencephalographic seizures, whether associated with clinical manifestations or not, were highly correlated with poor outcomes. The significance of these EEG findings was similar in both term and preterm infants. The study demonstrates that the EEG is predictive of outcome following neonatal seizures. PMID- 2578928 TI - The effect of continuous voluntary activation on neuromuscular transmission: a SFEMG study of myasthenia gravis and anterior horn cell disorders. AB - In normal subjects the neuromuscular jitter does not increase during continuous voluntary activation. In patients with myasthenia gravis, spinal muscular atrophy and motor neurone disease we have found that the neuromuscular jitter may increase during recordings of several minutes of continuous voluntary activation at steady innervation rates. In some units this led to impulse blocking, and in other units an initially normal jitter increased beyond the normal range. Measurement of jitter during continuous voluntary activation at steady innervation rates provides relevant information in the evaluation of neuromuscular transmission and fatigue in these disorders. PMID- 2578929 TI - Marked episodic elevation of cerebrospinal fluid pressure during nocturnal sleep in patients with sleep apnea hypersomnia syndrome. AB - The CSF pressure was measured continuously at the lumbar level during nocturnal sleep in 3 patients with sleep apnea hypersomnia syndrome. Nocturnal sleep was very unstable with frequent episodes of obstructive sleep apnea. When the patients were awake and relaxed in the supine position, their CSF pressure was stable and within the normal range. Episodic marked elevations of CSF pressure occurred frequently during sleep, and each elevation was preceded and accompanied by an episode of sleep apnea or hypopnea. Significant correlations were found between the duration of apneic episodes and increase of CSF pressure, and between decrease of SaO2 or TcPO2 and increase of CSF pressure. The duration of sleep apnea was longer, increase of CSF pressure was greater, and decreases of SaO2 and TcPO2 were more marked during REM sleep than during NREM sleep. It is suggested that the frequent marked episodic elevations of CSF pressure are caused by an increase in the intracranial vascular volume occurring mainly in response to transient hypercapnia and hypoxia, which are induced by pulmonary hypoventilation during the episodes of sleep apnea. PMID- 2578930 TI - Ambulatory monitoring of the electroencephalogram in high altitude mountaineers. AB - Twenty-nine 24 h ambulatory EEG recordings were obtained from 9 British Army mountaineers at heights ranging from 4115 to 6220 m during the period of acclimatization. Three individuals also had ambulatory sea-level EEGs. Sea-level clinical recordings were made on all the mountaineers. All the high altitude EEG recordings were readable and accurate sleep stage scoring was possible on 28 recordings. No paroxysmal activity, which had been reported previously, was noted in any of the high altitude EEGs. There was a marked reduction in stage 4 sleep compared to the amounts normally attained at sea-level, despite strenuous activity which might have been expected to increase slow wave sleep. There was a lesser reduction of REM sleep. These findings are consistent with complaints of poor quality sleep at high altitude, despite ample opportunity for sleep and the maintenance of health. The latter was attributed to careful acclimatization. PMID- 2578931 TI - Turns analysis (peak ratio) in EMG using the mean amplitude as a substitute of force measurement. AB - Several modifications of turns and mean amplitude analysis of the electrical activity of muscles have been suggested to avoid measurement of force. Previously we have shown that these modifications may overlook abnormalities if the analysis is performed at high force. A new modification is suggested: analysing the maximal value of the ratio of turns to mean amplitude (peak ratio), using the mean amplitude as an indication of force. It has been applied to a material in which the force was measured. The peak ratio was increased in 82% of 17 patients with myopathy and decreased in 36% of 14 patients with neurogenic disorders. PMID- 2578932 TI - Electroencephalographic spectral power and lateralized motor activities. AB - The powers of the theta (3.5-7 Hz), alpha (7.4-12.3 Hz) and beta 1 (12.9-14.8 Hz) rhythms were analysed in symmetrical derivations. Sixteen right-handed young male adults were observed: at rest, with eyes closed (EC) (4 sequences) and eyes open (EO) (4 sequences); during right then left tonic alternate or sequential movements of the hand and while gazing to the right then to the left. At rest there exists a clear and significant spectral dominance to the right which does not appear in all the rhythms or in all the derivations. As far as the alpha rhythm EC is concerned, individual analysis of the sequences shows that of those which are significantly lateralized, three-quarters are lateralized towards the right. Right motor activity exaggerates, left motor activity diminishes, this right electrical dominance. Lateral gaze is the most powerful activity in this respect. At each derivation, comparison of intensities during right and left activities shows that the contralateral movements diminish the spectral power in the 3 bands studied. This effect seems to be obtained most frequently at the centro-parietal level. The spectral power at rest compared with that during motor activity is higher constantly for theta rhythm, in almost half the cases for the alpha and occasionally for the beta 1. PMID- 2578933 TI - Spontaneous termination of ad libitum sleep episodes with special reference to REM sleep. AB - The spontaneous terminations of 72 ad libitum sleep episodes, recorded from 9 young adults, were analysed with respect to their proximity to REM sleep periods. Sleep episodes occurred throughout the 24 h day as a result of the experimental design, in which subjects were confined to bed for 60 continuous hours. For the group, sleep terminations occurred from REM sleep significantly more often than would be expected by chance (40% of the time). However, substantial individual differences in 'style' of sleep termination were observed, with 4 subjects contributing 82% of all terminations from REM sleep. Such individual differences were noted also in the tendency to exhibit brief interruptions of ongoing REM episodes. Both terminations of sleep from REM and brief interruptions of REM showed a general tendency to occur prior to about halfway through a REM sleep episode. The tendency to awaken differentially from REM sleep is interpreted on the basis of REM sleep providing the optimal physiological conditions for the transition from sleep to waking. PMID- 2578934 TI - Spontaneous cerebellar nuclei PGO-like waves in natural paradoxical sleep and under reserpine. AB - PGO-like spikes were described in chronically implanted cats at the cerebellar nuclei, dentatus, fastigii and interpositus, bipolarly and monopolarly recorded during natural paradoxical sleep. They showed close similarities with known PGO at occipital cortex and lateral geniculate nucleus: wave form, duration and amplitude were coincident. Moreover fast activity frequency increment in the last part of slow wave sleep also was observed at cerebellar loci. The peak-to-peak latency measurements demonstrated that the occipital cortex PGO lagged the nucleus dentatus PGO-like waves in 20-22 msec. The phasic cerebellar waves were not always related to eye movements. Acute experiments with a previous low dose of reserpine showed the PGO-like spikes when an exploring electrode penetrated a cerebellar nucleus. Chronically implanted cats, treated with reserpine, showed the phasic cerebellar waves during wakefulness and, after a few days, during the recovered paradoxical sleep. Based on electrophysiology and the reserpine experiments a common pontine generating mechanism for PGO and cerebellar PGO-like activity is proposed. It is also hypothesized that the cerebellum could participate in sleep physiology mainly related to phasic events without excluding a tonic function. PMID- 2578935 TI - Visual field perimetry analysis using evoked potentials in normal and corpus callosum sectioned cats. AB - The use of the visual evoked potential (VEP) was investigated in terms of its ability to accurately reflect the behaviorally determined extent of the visual field in non-verbal subjects. Two major adult groups of cats were studied: normals, and those with neonatal section of the corpus callosum at 15-19 postnatal days of age. A light-emitting diode was used as the visual stimulus. For both groups, the VEP determined monocular visual field extent closely matched the behaviorally determined field extent (Elberger 1979). This indicates that the VEP method is accurate, and that it is sensitive enough to detect differences between different populations of subjects. PMID- 2578936 TI - The effects of hypothermia on the latencies of the auditory brain-stem response (ABR) in the rhesus monkey. AB - The effect of hypothermia on the ABR latencies was evaluated in 14 rhesus monkeys. Data from 6 preliminary experiments showed that middle ear pressure decreased with decreasing body temperature and consequently, all experiments were conducted on animals with tympanostomy tubes inserted to maintain constant middle ear pressure. All animals were sedated with curare and anesthetized with ketamine. Hypothermia was induced by applying ice packs to the animal's body. Rectal temperatures and the ABR to click stimuli were recorded at 3-5 min intervals over a temperature range of from 38 degrees C to 20 degrees C. The pattern of latency change is characterized by increasing latency with decreasing temperature, a greater rate of change for temporally later waves and increasing rate of change for any one wave with decreasing temperature. An exponential function was applied to the data and explained at least 93% of the variances in latency. In general, a single exponential identical for all waves of an animal explained the latency change between 37 and 26 degrees C. Below 26 degrees C, a second and sometimes a third function was required. These findings are similar to those reported previously and to those describing the effect of maturation on the ABR. PMID- 2578937 TI - A study of spontaneous and evoked activity in the rat hippocampus under helium oxygen high pressure. AB - High pressures affect the physiology of the central nervous system. For a better understanding of this effect, we examined the hippocampal activity in the rat under high pressures (91 bars) of helium-oxygen. Effects of high pressure on hippocampal physiology are: an abnormally sustained 5-8 Hz pattern of spontaneous activity, followed, in some cases, by seizures; a marked decrease in the responses of CA1 pyramidal cells to stimulation of their commissural afferents; and a 50% decrease in the afterdischarge threshold. On the basis of the relatively well understood hippocampal physiology in normobaric conditions, our observations suggest that high pressures induce hypoexcitability of afferents and/or target cells. PMID- 2578939 TI - Automated morphological analysis by means of dynamic time-warping. AB - A new technique for the clustering of EEG wave forms is proposed. This method, termed dynamic time-warping (DTW) based clustering, involves the determination of a distance measure by allowing a certain degree of flexibility in the time axes of the two waves to be compared. Sharp waves and spikes, taken from actual EEG data, were subjected to the DTW-clustering approach. The results were compared with an approach based on features extracted from the wave forms and one based on computing the peak-aligned difference between wave forms. It was found that the DTW approach resulted in more homogeneous clusters than the other two approaches. These results, although preliminary, clearly indicate the feasibility of applying this new method for wave form clustering. PMID- 2578938 TI - A computer-assisted method for averaging movement-related cortical potentials with respect to EMG onset. AB - The recording of movement-related cortical potentials (MRCP) relies on the use of EMG activity or some other index of movement as a trigger for averaging. EMG activity can vary considerably from one movement to the next, particularly in patients with movement disorders. This results in an MRCP formed from individual sweeps which are averaged with respect to differing periods during the EMG activity. We describe a computer-assisted method for identifying EMG onset associated with each movement made by the subject. The method allows the experimenter to reject trials associated with artefacts or with spurious trigger pulses produced by resting EMG activity. It is also possible to average the MRCP into categories associated with differing EMG characteristics such as EMG duration, peak EMG amplitude and the duration from EMG onset to peak. Using this method we have been able to record reliable MRCP from patients with movement disorders in whom this would otherwise have been technically impossible. PMID- 2578942 TI - Maturation of the brain-stem auditory evoked potential in premature infants. AB - Patterns of development and extent of variability of the brain-stem auditory evoked potential (BAEP) are described in 52 healthy premature infants and 50 normal term newborns with reliable conceptional ages. Binaural and monaural stimulation are compared. Serial studies of individual prematures are emphasized and demonstrate that the most consistent and least variable measures are the monaurally derived interpeak intervals. All the BAEP parameters studied mature including wave form, relative amplitude, peak and interpeak intervals, but there is far more variability in preterms than in term infants or adults, even when infants are carefully matched for conceptional age. As term is approached, BAEP variability decreases substantially, suggesting that near term the BAEP becomes a more reliable indicator of neurologic function. The variability of the BAEP in the normal preterm limits its usefulness in determining neurologic dysfunction in individual high risk infants. Nevertheless, the BAEP may still prove useful for defining group differences among infants and could provide an objective measure of those factors influencing neurologic development. Serial change in the BAEP is a specific parameter which we believe merits further study in premature infants as an index of neurologic maturation. PMID- 2578940 TI - About the origin of cerebral somatosensory potentials evoked by Achilles tendon taps in humans. AB - This study examines the effects of ischemic hypoxia and cooling of the leg, muscle contraction and vibration on cerebral potentials evoked by Achilles tendon taps and posterior tibial nerve stimulation to obtain indirect evidence leading to the identification of receptors activated by tendon taps. Experiments performed during ischemia of the leg showed that these receptors lie between the ankle and the knee. Cooling of the leg showed that they are located deep in muscles or bone. Experiments performed during vibration and muscle contraction suggest that muscle stretch receptors provide the afferent input responsible for Achilles tendon tap evoked potentials. All of these experiments point to primary muscle spindles in the proximal gastrocnemius-soleus muscle belly as the main source of afferent input for evoking cerebral potentials to Achilles tendon taps in humans. PMID- 2578941 TI - Maturation of contralateral brain-stem responses in preterm infants. AB - Average auditory brain-stem responses (ABRs) evoked by left and right ear stimulation of varying intensities were recorded from ipsilateral and contralateral scalp placements in human neonates. Subjects included pre-term infants, healthy full-term infants and high risk, full-term infants. Pre-term infants were classified into 4 age groups ranging from 29 to 41 weeks post conceptional age (PCA). Significant ipsilateral/contralateral differences were observed. Further, this effect was highly dependent upon age. The youngest pre term infants were devoid of contralateral activity despite robust ipsilateral responses. The emergence and evolution of the contralateral wave form could readily be visualized from 31 to 37 weeks PCA. The contralateral response was uninfluenced by stimulus intensity but appeared to be related to the amplitude of the ipsilateral response. No systematic ear differences were noted. Pre-term infants tested between 38 and 41 weeks PCA (term equivalence) showed some persisting immaturity in terms of the ABR. Healthy and sick full-term infants were indistinguishable with respect to ipsilateral or contralateral potentials. On the other hand, very ill 6-week-old infants showed specific contralateral abnormalities. PMID- 2578943 TI - Uncertainties of topodiagnosis of auditory nerve and brain-stem auditory evoked potentials due to rarefaction and condensation stimuli. AB - Auditory nerve and brain-stem auditory evoked potentials (AN and BAEP) were elicited after separate stimulation with rarefaction and condensation stimuli. There were only few persons with identical patterns in the two opposite phases. Rarefaction stimuli showed a tendency to evoke AN and BAEP with shorter latencies and better synchronization. In diseases of the auditory nerve and brain-stem the phase-dependent differences were even more prominent, indicating different topodiagnostic levels of lesions. The results point to the need for stimulus presentation with rarefaction and condensation stimuli separately and an evaluation of both curves. The alternating mode is the result of summating rarefaction and condensation stimuli. PMID- 2578944 TI - The effects of aging on the P3 component of the visual event-related potential. AB - Visual stimuli were used to elicit ERPs in 108 normal subjects ranging in age from 8 to 90 years. Age-related differences were found for both P3 latency and amplitude. Children and elderly adults were found to have the latest P3s. The earliest P3s were found in subjects in their twenties. A curvilinear function best described the P3 latency/age relationship. Also, small but significant differences were observed between males and females in P3 latency. The relationship between P3 amplitude and age was strongly influenced by scalp location. P3 was largest at posterior electrode sites, but was not visible at frontal sites in young children. With increasing age P3 decreased in amplitude at the posterior sites and increased in amplitude at more frontal locations. PMID- 2578945 TI - Visual evoked potentials in the great apes. AB - Visual evoked potentials (VEPs) in response to flash stimuli were recorded from occipital and central-scalp electrodes in the chimpanzee and gorilla. The most notable occipital component of the VEP was a surface-positive wave (P90), the latency of which decreased with development. Central scalp responses, apparent only in older animals, included a characteristic long-latency 'vertex wave' (N125 P225). Observed responses are similar to those reported for humans and monkeys, but appear to share more specific features of human VEPs. PMID- 2578946 TI - Further investigation of visual evoked potentials elicited by lateralized stimuli: effects of stimulus eccentricity and reference site. AB - Visual evoked potentials (VEPs) to small lateralized flashes were recorded from the parietal midline, homotopic lateral central and occipital electrodes, and from left and right mastoid processes, all referred to a balanced non-cephalic reference. Two stimulus eccentricities, 4 degrees and 10 degrees, were employed, and a comparison made between the non-cephalic and linked mastoid references. P120 (measured at lateral occipital sites only) peaked earlier and was of smaller amplitude at the electrode contralateral to the visual field of stimulus exposure. N160 peaked earlier at central than occipital sites, was larger from electrodes over the contralateral hemisphere, and at the occipital sites only, peaked earlier in the electrode contralateral to the visual field of stimulus exposure. These effects were virtually unaffected by the eccentricity manipulation and it is concluded that light scatter across the visual midline is unlikely to be responsible for the observed pattern of ipsilateral-contralateral VEP asymmetries. The mastoids were found to detect significant stimulus-locked activity in the same latency range as the occipital N160 component. However, comparison of the non-cephalic and linked mastoid references revealed only non specific effects, and no sign of any change in the pattern of ipsilateral contralateral VEP asymmetries, or the magnitude of the associated latency differences. It is concluded that these effects may be of value in the study of callosal transfer. PMID- 2578947 TI - Clinical relevance of long-latency SEPs and VEPs during coma and emergence from coma. AB - Follow-up measurements of long-latency visual (VEP) and somatosensory (SEP) evoked potentials were performed on 30 comatose patients. Twenty-seven of the patients had severe head injury, 2 had encephalitis and 1 was in a posthypoxic state. For the SEP study a mechanical vibration stimulus was used, applied 60 times at intervals of 10 sec. The same rate was used for visual stimulation. The late EP components were classified by a signal-to-noise ratio (SNR), whereby an SNR of less than 2.6 is characteristic of a questionable or unmeasurable EP and an SNR greater than 2.6 is evidence of a clearly existing EP; the clinical state was scored using the Glasgow Coma Scale (GCS); the patient outcome was assessed 6 months after the injury using the Glasgow Outcome Scale. The highest correlation (r = 0.72) was found between the clinical state, represented by the GCS, and the SEP. A similar correlation (r = 0.66) was obtained between the GCS and the vertex VEP. The occipital VEP showed no correlation. Emergence from coma and recovery was accompanied by an increase of the SEP and an increasing spread of the VEP over the whole scalp. Most patients with a clear long-latency SEP in coma had a favourable outcome; a missing or a questionable SEP indicated a poor outcome. PMID- 2578948 TI - Early evoked potentials detected from the scalp of man following infraorbital nerve stimulation. AB - Stimulation of the infraorbital nerve evoked a short latency scalp response characterized by a large amplitude triphasic potential (W1), followed by two smaller negative deflections (W2 and W3). All these waves were presynaptic in origin (as shown by double pulse stimulation), but appeared to be generated by separate dipoles. Short distance bipolar recording showed that W1 travelled from the zygoma to the mastoid. This wave was thought to be generated in a nearby neural structure, presumably the proximal part of the maxillary nerve, the gasserian ganglion and possibly even the trigeminal root. W2 and W3 components were probably generated by the trigeminal root fibres running through the brain stem. Their origin from slowly conducting trigeminal fibres was ruled out by their absence in short distance bipolar records along the line from the zygomatic bone to the mastoid process, and by studies on their thresholds, which were shown to be identical to those of W1. Control experiments with concurrent facial muscle recording excluded any possible contamination of the scalp response to infraorbital nerve stimulation by electromyographic activity, and demonstrated gross muscular artefacts, picked up as far-field activity by scalp electrodes, following electrical stimulation of the upper lip. PMID- 2578949 TI - Absence of detectable chorionic gonadotropin subunit messenger ribonucleic acids in the rat placenta throughout gestation. AB - We hypothesized that if a CG similar in structure to other glycoprotein hormones was present in the rat placenta, then mRNAs encoding its subunits would be detectable. To investigate the possible presence of a CG in the rat, we attempted to detect mRNAs encoding the alpha- and CG beta-like subunits in the placentae of timed pregnant rats by sensitive blot hybridization analyses using cloned cDNAs encoding alpha- and beta-subunits of LH derived from rat pituitary mRNA. No subunit-specific mRNAs in placentae of pregnant rats at 4-21 days gestation were detected at either high or low stringencies of hybridization. However, under similar conditions, subunit-specific mRNAs were readily observed in total pituitary RNA of normal as well as ovariectomized rats. Moreover, hybridization with a cDNA for alpha-tubulin, a major component of the cytoskeleton, yielded easily detectable bands in rat placental RNA. In addition, hybridization analysis, under low stringency conditions, of restriction enzyme digests of rat genomic DNA with a rat LH beta-cDNA, which would detect LH beta subunit-like genes, suggests the presence of a single gene that, in fact, encodes the rat LH beta-subunit. We conclude that mRNAs encoding for proteins structurally homologous to rat LH subunits are absent in the rat placenta and that only a single LH beta-like gene is present in the rat. The luteotropic activity associated with the rat placenta must be related to a gonadotropin-like hormone whose structure is dissimilar from that of CG. PMID- 2578950 TI - Effect of sodium vanadate on deoxyribonucleic acid and protein syntheses in cultured rat calvariae. AB - Sodium vanadate, an agent known to have multiple cellular actions, was studied for its effects on aspects of bone formation in cultures of 21-day-old fetal rat calvariae. Vanadate (0.1-10 microM) stimulated the incorporation of [3H] thymidine into acid-insoluble residues (DNA); the effect appeared after 3 h and was sustained for 96 h. Vanadate increased the bone DNA content and mitotic index. Treatment with vanadate at 10 microM for 24 h or at 0.3-1 microM for 96 h increased the incorporation of [3H]proline into collagenase-digestible protein (CDP), but the effect was not specific for collagen; vanadate also increased the labeling of noncollagen protein (NCP). Vanadate increased the incorporation of [3H]proline into type I collagen without affecting other collagen types. Vanadate (100 microM) caused a marked and irreversible inhibitory effect on the labeling of DNA, CDP, and NCP. Treatment with vanadate at multiple doses for 3-96 h did not stimulate alkaline phosphatase activity, but this enzyme was inhibited in bones exposed to 1 mM vanadate for 24 h or 10 microM vanadate for 96 h. The stimulatory effect on DNA labeling was primarily observed in the periosteum, while that on CDP labeling was seen only in the periosteum-free bone. These studies indicate that sodium vanadate stimulates bone DNA, collagen, and NCP syntheses in vitro, although high doses of vanadate have an irreversible inhibitory effect. PMID- 2578952 TI - Contribution by the glycogen pool and adenosine 3',5'-monophosphate release to the evanescent effect of glucagon on hepatic glucose production in vitro. AB - To elucidate in vitro the transience of glucagon-induced hepatic glucose release, the effects of glucagon on hepatic glucose production and cAMP release were evaluated in the isolated rat liver preparation perfused by a nonrecirculating system. Glucagon was added to the infusate in stepwise increasing concentrations at 0, 60, and 100 min to give final concentrations of 2.5 X 10(-11), 10(-9), and 5 X 10(-8) M, respectively. Glucagon at 2.5 X 10(-11) M caused cAMP release [basal (mean +/- SD), 11.2 +/- 3.0 pmol/(min X 100 g BW)] to rise rapidly and plateau at 23.3 +/- 7.0 pmol/(min X 100 g BW), whereas hepatic glucose production [basal, 3.7 +/- 1.6 mumol/(min X 100 g BW)] increased only transiently to a maximum of 15.3 +/- 3.1 mumol/(min X 100 g BW) and fell thereafter. The enhanced cAMP release during the consecutive glucagon infusion was accompanied by a transient rise in hepatic glucose production during the second, but not during a third, glucagon infusion. When 3-isobutyl-1-methylxanthine, a potent phosphodiesterase inhibitor, was added to the perfusion medium (0.5 mM), the cAMP response to 2.5 X 10(-11) M glucagon was enhanced [247 +/- 124 pmol/(min X 100 g BW)] as was hepatic glucose production (+ 21%; P less than 0.05). Further augmentation of the glucagon concentration was followed by an increase in hepatic cAMP, but not glucose, release. When glucagon infusion (2.5 X 10(-11) M) was repeated with a glucagon-free period of 30 min in between, no stimulation of cAMP and consecutive glucose release was found during the second period. However, when the second glucagon dose was increased to 10(-9) M, glucose and cAMP release were again stimulated to the same extent as in experiments with no glucagon-free period in between. We conclude that the size of the glycogen pool and the cAMP concentration directly modulate hepatic glucose production and are responsible for evanescent glucagon action. This mechanism can be described by computer simulation. PMID- 2578953 TI - Interaction of triiodothyronine-receptor complexes with simian virus 40 minichromosomes in monkey kidney CV-1 cells. AB - Thyroid hormone-responsive tissues contain chromatin-localized receptors that bind to DNA and may associate preferentially with actively transcribed chromatin. To study such receptor-chromatin localization, we have used cultured CV-1 cells permissive for simian virus 40 (SV40), in which viral minichromosomes can be separated from the cellular chromatin. CV-1 cells were found to contain intranuclear thyroid hormone-binding sites with an affinity for T3 and T4 and a site concentration similar to those in other thyroid hormone-responsive tissues. When these cells were infected with SV40 or an SV40-human GH gene recombinant, T3 did not affect SV40 replication, early or late gene transcription, or human GH gene expression. However, in both cases, these infections resulted in the association of about 7.5% of the total specific T3-binding activity with the SV40 minichromosome, representing about 1 receptor molecule/65 minichromosomes and a 10-fold enrichment over the cellular chromatin-associated activity (4.3 fmol/micrograms SV40 minichromosomal DNA vs. 0.43 fmol/micrograms chromosomal DNA); 30% of this could be covalently cross-linked to the minichromosome with dissuccinimidyl suberate. The minichromosomes were also found to be transcriptionally active. Thus, thyroid hormone receptors interact preferentially with the SV40 minichromosome, possibly owing to their tendency to associate with transcriptionally active chromatin. This system provides an alternate approach to study the association of thyroid hormone receptors with defined chromosomal segments. PMID- 2578951 TI - Regulation of the alpha and thyrotropin beta-subunit messenger ribonucleic acids by thyroid hormones. AB - We studied the regulation of mRNAs encoding the alpha- and beta-subunits of TSH by thyroid hormones (T4 and T3) in mouse thyrotropic tumors and pituitary glands. Hypothyroid male (LAF1) mice bearing thyrotropic tumor (TtT97) were injected daily with T4 for 0, 1, 5, 12, or 33 days. After day 33, plasma levels of TSH and free (unassociated) TSH beta-subunit were reduced to less than 1% of control levels, whereas free alpha-subunit was reduced to 6% of control levels. Steady state levels of subunit mRNAs in extracts of the thyrotropic tissues were measured by blot hybridization analyses using mouse subunit-specific cloned cDNAs. Treatment of mice with T4 caused a rapid decline in the levels of tumor mRNAs for both alpha and TSH beta; after day 1, alpha and TSH beta mRNA levels decreased to 35% and 10% of control values, respectively. Levels of TSH beta mRNA were undetectable after 5 days of T4 treatment, whereas levels of alpha-subunit mRNA remained at 30-35% of control levels even after day 33. In a separate experiment, TSH beta mRNA decreased to 42% of the control level (P less than 0.05), whereas alpha-subunit mRNA remained at 64% of the control level (P = NS) 4 h after a single injection of T4. Finally, T3 also caused a rapid decrease in the levels of both subunit mRNAs in the anterior pituitary glands of hypothyroid mice, but the effect was more complete on TSH beta mRNA levels. We conclude that thyroid hormones have rapid suppressive effects on the levels of mRNAs encoding the subunits of mouse TSH in the thyrotrope. The suppressive effects of thyroid hormones occur more rapidly and are greater for TSH beta than alpha-subunit mRNAs. The parallel changes observed in the subunit mRNA levels and the plasma subunit protein levels in animals treated with thyroid hormones suggest that the changes in the plasma levels of TSH and subunits may reflect effects of thyroid hormones on TSH gene expression in addition to effects on secretion. PMID- 2578954 TI - Effects of gamma-globulin therapy in severely epileptic children. AB - The effects of gamma-globulin therapy have been studied from clinical, immunological, and electrographic perspectives in 10 children affected by severe organic epilepsy. After the first or the second injection of large doses of IgG, an appreciable reduction in seizure frequency and an improvement in behavioral and psychological performance were observed in seven children. These clinical modifications were not correlated with an important decrease of the EEG epileptic elements, but in most cases they were associated to an increase in alpha activity and/or in power of the predominant EEG frequency. These changes were observed during the entire treatment period and tended to disappear when therapy was interrupted. No significant changes in both immunological data and plasma levels of antiepileptic drugs accompanied the clinical and EEG changes. PMID- 2578955 TI - Differences in chlorophyll-protein complexes and composition of polypeptides between thylakoids from bundle sheaths and mesophyll cells in maize. AB - Thylakoids from enzymatically separated bundle sheath and mesophyll tissue chloroplasts were examined for their chlorophyll-proteins by tube sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE). Differences were found in distribution of chlorophyll among peaks. The chlorophyll-protein a peak (CPa), considered to be the photosystem II (PSII) reaction centre by many authors, was seen to be absent in bundle sheath thylakoid samples. The slab SDS-PAGE revealed the absence of the polypeptides present in PSII preparations of chloroplast subfractions having only PSII activity. This finding confirms Anderson's hypothesis of the structure of grana and stroma thylakoids. PMID- 2578956 TI - Induction of size reduction in Escherichia coli by near-ultraviolet light. AB - Escherichia coli AB1157 cells, growing exponentially at 37 degrees C in 63B1 medium (supplemented with glucose and casamino acids) with a doubling time of 50 min, were subjected to continuous illumination with 366-nm light at a fluence of 1.5 kJ . m-2 X min-1. Under these conditions, the growth rate decreased and after 1 h of illumination, a new stable exponential mode was reached with a doubling time of 73 min. This reduction in growth rate occurred without any change in the rate of cell division for two generations after the beginning of illumination. Survival was unaffected, implying that cell size must have decreased. This was confirmed with size distribution curves of control and illuminated cells obtained with a Coulter counter. Furthermore electron micrographs of negatively stained cells indicated that illumination results in a 30-40% decrease in cell length, the diameter increasing by 8%. Hence 366-nm light uncouples growth and division rates. Illumination under the above conditions triggered the accumulation in vivo of 8-13-linked tRNA. The stationary level of the 8-13 link, 80% of the maximal level, was reached precisely when the growth rate reached its new stable value. Furthermore, no reduction in growth rate occurred in a nuv- cell lacking 4 thiouridine in its tRNAs. Hence we conclude that the 366-nm photons trigger partial tRNA inactivation with consequent slowing down of protein synthesis and accordingly of the cell growth rate. In addition, the stringent response has at most a minor effect. In conclusion, near-ultraviolet light is able to decrease the rate of cell growth by restricting the availability of charged tRNAs, and this occurs without affecting the cell division rate. PMID- 2578957 TI - Regulation of ppp(A2'p)nA-dependent RNase levels during interferon treatment and cell differentiation. AB - The intracellular effector oligonucleotides ppp(A2'p)nA (n = 2- greater than or equal to 4) regulate the breakdown of RNA by activating ppp(A2'p)nA-dependent RNase. Cellular levels of this RNase were demonstrated to be regulated during differentiation of murine embryonal carcinoma cells. An induction of this RNase by interferon was demonstrated in each of three differentiated cell types (F9 clone 9, PYS, and PSA 5E) by analyzing rRNA breakdown following the introduction of ppp(A2'p)nA into the intact cells. In contrast, in three undifferentiated embryonal carcinoma cell lines (F9, PC13 clone 5, and Nulli 2A) there was little if any ppp(A2'p)nA-dependent RNase either with or without interferon pretreatment. These results were confirmed by affinity labeling of the RNase in cell-free systems. Addition of the proteinase inhibitor, leupeptin, to the cell lysis buffer was necessary to stabilize the RNase against cleavage to discrete breakdown products. Moreover, during differentiation of PC13 clone 5 cells by retinoic acid and N6,O2'-dibutyryl-adenosine 3',5'-monophosphate there was a gradual induction of ppp(A2'p)nA-dependent RNase. The expression of this RNase is, therefore, greatly enhanced during cell differentiation. In addition, the double-stranded-RNA-dependent protein kinase was investigated and was found to be interferon-inducible in all of the cell lines regardless of the state of cell differentiation. PMID- 2578959 TI - A crystalline synthetic peptide representing the epitope of a monoclonal antibody raised against synthetic interferon-alpha 1 fragment 111-166. AB - The antigenic determinant recognized by the monoclonal antibody that had been raised against synthetic human interferon-alpha 1 (IFN-alpha 1) fragment 111-166 [Arnheiter, H., Thomas, R.M., Leist, T., Fountoulakis, M., and Gutte, B. (1981) Nature (Lond.) 294, 278-280] and that cross-reacted with human IFN-alpha 1, IFN alpha 2, and IFN-alpha A made in Escherichia coli, was localized to the region between residues 151 and 166 using synthetic COOH-terminal interferon fragments. In solid-phase radioimmunoassays neither the strongly hydrophilic COOH-terminal nonapeptide IFN 158-166 nor its mixtures with IFN 151-162 or IFN 149-158 showed any measurable interaction with the antigen binding site of the monoclonal antibody. For antibody binding, the full covalent structure of IFN 151-166 was required. Quantitatively very similar results were obtained with IFN 149-166 and IFN 143-166. The synthetic COOH-terminal hexadecapeptide of human IFN-alpha 1 (IFN 151-166) could be crystallized. PMID- 2578958 TI - Specific fragmentation of tRNA and rRNA at a 7-methylguanine residue in the presence of methylated carrier RNA. AB - The reaction of site-specific cleavage of tRNA at a 7-methylguanine residue, including subsequent treatment with sodium borohydride and aniline [Wintermeyer, W. and Zachau, H.G. (1975) FEBS Lett. 58, 306-309], was shown to work only within a certain range of tRNA concentrations (higher than 30 microM). The Escherichia coli 16S rRNA, which contained a unique m7G (position 527), could not be split by this method when taken at any concentration. It was found that the presence of statistically methylated carrier RNA in the reaction mixture at the borohydride stage significantly stimulates site-specific fragmentation of 16S rRNA and 32P labeled tRNAs. Direct sequencing proved that 16S rRNA and tRNA are cleaved by this procedure successfully at the m7G residue. The E. coli 16S rRNA was preparatively cleaved by the described procedure into two fragments. The 5' terminal fragment (1-526) and the 3'-terminal fragment (528-1542) were isolated in the pure form and their secondary structure investigated by the circular dichroism method. The results of this study showed that the secondary and tertiary structures of the 5'-terminal one-third of the 16S rRNA are at least as ordered as those of intact 16S rRNA or its 3'-terminal two-thirds. PMID- 2578960 TI - Mitochondrial transcription and processing of transcripts during release from glucose repression in 'resting cells' of Saccharomyces cerevisiae. AB - Mitochondrial transcription and processing of transcripts have been investigated at different stages of release from glucose repression in resting cells of Saccharomyces cerevisiae. Transcripts were identified by hybridization with nick translated or terminally labelled gene-specific probes. This allowed the determination of the steady-state levels of individual transcripts in the mitochondrial RNA population. Results showed different gene-specific patterns of response to respiratory induction: no increase in the level of transcripts (oxi2); a rapid increase in the steady-state levels of all transcripts (cob); a very strong increase in the processing of the high-molecular-mass precursors (oxi3 and oli2); an increase in the level of stable circular transcripts (oxi3). As a whole the results indicate specific and differentiated effects of release from glucose repression on the expression of the different mitochondrial genes and demonstrate the importance of processing events in mitochondrial regulation. PMID- 2578962 TI - Influence of pancreatic duct occlusion on islet hormones in peripheral and portal plasma and in the pancreas of the mini-pig. AB - In a total of 18 'Gottingen' mini-pigs we studied basal glucose in the peripheral plasma, and the hormones insulin, glucagon, and somatostatin in the peripheral and portal plasma, as well as in extracts of pancreatic tissue, both in animals subjected to pancreatic duct occlusion with prolamine (Occ pigs) 9 months previously and in controls. Additionally, in the pancreas the relative frequency of A-, B-, D- and PP-cells was determined by immunocytochemistry. In peripheral blood of Occ pigs glucose, insulin, and somatostatin were unchanged, while glucagon was decreased. Also after occlusion the portal plasma revealed an increase in insulin but unchanged glucagon and somatostatin, while in the pancreatic tissue insulin and glucagon were statistically unchanged, but somatostatin was reduced. The relative frequency of A-, B-, D- and PP-cells in the pancreatic islets was comparable in both control and Occ pigs. It is concluded that also in the pig pancreatic duct occlusion leads to atrophy of the exocrine pancreas, but leaves undisturbed basal blood glucose, insulin, glucagon and islet cells. PMID- 2578961 TI - Amino acid sequence of the non-collagenous globular domain (NC1) of the alpha 1(IV) chain of basement membrane collagen as derived from complementary DNA. AB - NC1, the C-terminal non-collagenous globular domain of collagen IV, represents one of the two end regions responsible for the assembly and cross-linking of the extracellular network of basement membrane collagen. Several cDNA clones for the NC1 domain of the alpha 1(IV) collagen chain of mouse have been isolated by using synthetic oligonucleotides as screening probes for mouse libraries. The oligonucleotides were synthesized according to known stretches of the corresponding protein sequence. Sequencing of the overlapping cDNA clones allowed the complete amino acid sequence of the NC1 domain to be deduced as well as the C terminal 165 amino acid residues of the triple helix. It consists of 229 amino acid residues which comprise two homologous regions with a high content of cysteine. These DNA and protein sequences are compared to the corresponding sequences of other collagens and discussed with respect to their structural and biological significance. PMID- 2578963 TI - Comparison of the in vitro cytotoxicity (L1210) of 5-aza-2'-deoxycytidine with its therapeutic and toxic effects in mice. AB - The in vitro and in vivo cytotoxic effects of 5-aza-2'-deoxycytidine (DAC) on L1210 leukemia are reported and related to the pharmacokinetics of DAC in CDF mice. L1210-bearing mice (1 X 10(4) cells, i.v.) given DAC i.v. (6.5-225 mg/kg) on day 3 showed a 50-212% increase in lifespan (ILS), with an estimated 3-6 log cell kill of L1210. Optimal effects with late treatment were obtained when DAC was given either on a multiple-dose regimen (10 mg/kg i.v., q 3 hr X 4, day 3 or 5) or by a constant s.c. infusion (2.0 mg/kg/hr X 12 hr, day 3), ILS 328-414%. Following 10 or 100 mg/kg i.v., plasma DAC declined in a triexponential manner with an intermediate elimination t 1/2 of 31 min. Urinary excretion accounted for 28.5% of DAC plasma clearance. When L1210 cells were exposed to DAC in vitro (0.5 100 micrograms/ml for 24-120 hr) a maximum 3-4 log cell kill was obtained. Both in vivo and in vitro response to DAC demonstrated the importance of exposure time as a determinant of cell kill. DAC is estimated to be more cytotoxic in vivo than in vitro. The critical cytotoxic concentration of DAC appears to be between 0.5 and 1.0 microgram/ml. PMID- 2578964 TI - Monoclonal antibodies specific for murine IgM. II. Activation of B lymphocytes by monoclonal antibodies specific for the four constant domains of IgM. AB - Seventeen monoclonal antibodies specific for IgM and one kappa light chain specific antibody were used to test the effect of immunoglobulin (Ig)-specific antibodies on B cell activation. In soluble form, either alone or together with T cell-derived growth and maturation factors, none of the antibodies stimulated resting B cells to divide or secrete Ig. The soluble antibodies inhibited lipopolysaccharide-induced B cell activation. The inhibitory effect of the antibodies was independent of their Fc part. When immobilized, the same antibodies could activate B cells to proliferate and together with T cell-derived maturation factors to mature to plasma cells. Occupation by immobilized antibody of determinants on any of the four constant region domains and on the light chain of surface Ig can lead to the stimulation of B cells. PMID- 2578965 TI - Immediate hypersensitivity to drugs and simple chemicals: the efficacy of monovalent elicitors. AB - Introduction of a reactive monohaptenic chemical into the sensitized organism will not normally result in elicitation of immediate reactions. Rather, the first products of chemical conjugation to suitable carriers in vivo are monohaptenic, conjugates which are inhibitory according to the bridging concept, stating that the initiating event for mast cell and basophil activation is a cross-linking of membrane-bound antibody by dihaptenic or oligohaptenic antigen. Simple calculations and quantitative data are presented to show that built-in inhibition is indeed a powerful barrier to any rapidly occurring allergenic manifestation which depends on the formation of divalent conjugates. If and when such a reaction does nevertheless occur, special requirements have to be invoked. One possibility is that the chemical or drug as such, i.e. without conjugation to a carrier, is an elicitor of anaphylaxis. Such compounds are known in a guinea pig passive cutaneous anaphylaxis model system, but there is evidence that they may also play a role in clinical situations. These monovalent elicitors possess in addition to the haptenic moiety an auxiliary group. The auxiliary group requirements were studied in the guinea pig passive cutaneous anaphylaxis system by using synthetic peptides with an N-terminal 2-carboxy-4,6-dinitrophenyl group as the hapten and phenylalanine and modified phenylalanine at the C-terminus as auxiliary group. The conclusions are that effective auxiliary function depends on the benzene ring and neighboring carboxyl groups in selected positions. Anaphylactogenicity is high when the haptenic and auxiliary groups can act independently, i.e. when separated by a peptide chain of considerable length. Potent anaphylactogens with close linkage of the two groups have, however, also been found. It is unlikely that the passive cutaneous anaphylaxis elicitations observed here are mediated by some form of indirect bridging of membrane-bound antibody. PMID- 2578966 TI - Molecular and antigenic heterogeneity of the rat leukocyte-common antigen from thymocytes and T and B lymphocytes. AB - The molecular forms and antigenic heterogeneity of the leukocyte-common antigen (L-CA) of rat lymphocytes have been analyzed. Thymocytes show one main band at 180 kDa, T cells four bands at 180, 190, 200 and 220 kDa and B cells one broad band at about 240 kDa. T helper and T cytotoxic cell subsets show the same four bands with some differences in the proportion of each. Four mouse monoclonal antibodies (MRC OX-1, 28, 29 and 30) reacted with all molecular forms of L-CA and fell into two sets that were noncompetitive in binding to L-CA (MRC OX-1, 28, 29 vs. OX-30). The antigenic determinants seen by all these antibodies were lost when L-CA was reduced and alkylated. Three antibodies (MRC OX-22, 31 and 32) reacted selectively with B cells, T cytotoxic cells and about 2/3 of T helper cells. OX-22 and OX-31 competed for binding but were noncompetitive with OX-32. All these antibodies bound to a subfraction of the 190, 200 and 220-kDa forms of T cell L-CA but not at all to the 180-kDa form of T cells or thymocytes. One antibody bound to B cells only (MRC OX-33) and precipitated a subfraction of B cell L-CA. With all the antibodies that did not label thymocytes the antigenic determinants survived reduction and alkylation. Subsequent proteolysis with trypsin then destroyed all determinants except the one reacting with MRC OX-22 antibody. In this case tryptic peptides retained full antigenic activity which was, however, destroyed by further proteolysis with pronase. PMID- 2578967 TI - Segregation of reactivity to the mitogens lipopolysaccharide, lipoprotein and dextran sulfate in clones of the B cell lymphoma line WEHI 279.1. AB - The B cell lymphoma line WEHI 279.1 (surface IgM+, I-A+ and I-E+) was used as a model system to analyze functional reactivity of B lymphocytes to mitogens. Among the mitogens tested, lipopolysaccharide (LPS), lipoprotein (LP), and dextran sulfate (DxS) all induced a strong, dose-dependent growth inhibition of tumor cells. The analysis of independently derived clones, however, revealed that mitogen sensitivity could be lost in the absence of detectable alterations in the expression of those surface markers. Moreover, reactivity to LPS, LP and DxS segregated independently in these clones, suggesting distinct triggering mechanisms and functional receptors for these mitogens on the B cell membrane. PMID- 2578968 TI - A study of mitochondrial and nuclear transcription with cloned cDNA probes. Changes in the relative abundance of mitochondrial transcripts after stimulation of quiescent mouse fibroblasts. AB - From a cDNA library constructed in pBR322 we have isolated and studied a set of clones corresponding to mRNAs whose abundance changes when serum-deprived murine fibroblasts are stimulated to enter the cell cycle. A subset of these clones was derived from mRNA species whose abundance decreased during the G1 period following serum stimulation; all but one of these clones turned out to be clones of mitochondrial poly(A)mRNAs. There was no detectable change in the rate of transcription of the mitochondrial genome compared with the nuclear genome, and the lengths of the poly(A) segments on both mRNA species did not change significantly after serum stimulation. We conclude that the apparent decline in the relative abundance of the mitochondrial mRNAs is the result of a relative increase in the processing and/or transport of nuclear mRNA. PMID- 2578969 TI - A monoclonal antibody identifies a glycoprotein complex involved in cell substratum adhesion. AB - The monoclonal antibody CSAT has been reported to perturb the adhesion of chick embryo cells to their substratum (Neff et al. [19]). Evidence is presented here that the antigen recognized by this monoclonal antibody is comprised of three membrane glycoproteins. The antigen is released from cells with non-ionic detergent and purified by monoclonal antibody affinity chromatography. When analysed by SDS-PAGE under non-reducing conditions, the antigen resolves into three components of apparent molecular weights 160 000 (band 1), 135000 (band 2), and 110 000 (band 3). Following reduction of each component, bands 1 and 2 migrate at slightly lower apparent molecular weights, while band 3 migrates at a higher apparent molecular weight, suggesting that band 3 has an internal disulfide bond. All three bands differ from one another as determined by peptide mapping and by immunologic cross-reactivity. It is postulated that the three glycoproteins function as a complex that plays a central role in cell-substratum adhesion. PMID- 2578970 TI - Isolation and characterization of nuclear particles containing rapidly labelled hnRNA and snRNA in combination with a distinct set of polypeptides of Mr 74000 and 72000. AB - A heterogeneous RNP structure has been isolated from rat liver nuclei by a method previously used for the isolation of 30S RNP complexes carrying heterogeneous RNA (hnRNA) [1]. The RNP sediments in sucrose gradients with s-values of 70-110S. Formaldehyde-fixed preparations band at Q = 1.40 in isopycnic CsCl gradients. The RNP structure is composed of a heterogeneous population of polypeptides, prominent among which are two proteins with Mr 74000 and 72000. It contains both rapidly labelled RNA as well as several species of snRNA, as demonstrated by double-labelling experiments and gel electrophoresis. Treatment of rats with alpha-amanitin leads to a significant decrease in the amount of recovered RNP. In the presence of 0.7 M NaCl the s-value of the complex changes from 70-110S to 40 80S. The RNP structure is stable to mild RNase A or micrococcal nuclease digestion. Transmission electron microscopy reveals the presence of a heterogeneous population of particles with a mean diameter of 300-360 A. The isolated RNP structure differs completely from the well-known monoparticle or polyparticle hnRNP complexes and from the 30S or smaller snRNP particles but could be similar to or identical with the heterogeneous complex described by Jacob et al. [29]. PMID- 2578972 TI - Intrasomatic and intradendritic recordings of plateau potentials in slices of the dentate gyrus maintained in vitro. AB - Intrasomatic and intradendritic recordings were performed in slices of the dentate gyrus maintained in vitro. When barium ions (2.4 mM) were substituted for calcium ions in the perfusing medium, plateau potentials appeared with an amplitude of 20-40 mV which lasted from 40 ms to more than one min; during these plateau potentials, the input membrane resistance was decreased. In the soma, plateau potentials were also observed in a medium containing barium ions + tetrodotoxin (0.3 or 0.6 microM); whereas, in the dendrites, the barium-induced plateau potentials were abolished after addition of tetrodotoxin to the barium containing perfusion. The somatic plateau potentials had a duration which appeared to be dependent on the stimulus frequency. After being in contact with the barium-tetrodotoxin solution for a long period, the soma membrane potential was observed to jump between two relatively stable levels: a resting state and a depolarized state. In conclusion, calcium conductances appear to be present both at the soma and the dendrites of dentate granule cells; however, at the dendritic level, it appears that, when sodium channel permeability is blocked by tetrodotoxin, there is insufficient inward current to support the generation of action potentials. PMID- 2578971 TI - Long-term oral therapy of asthma with terbutaline and theophylline, alone and combined. AB - Bronchodilation and side effects of 28 days treatment with either a full therapeutic dose of theophylline slow-release preparation 500 mg twice daily (400 600 mg), a slow-release terbutaline preparation 10 mg twice daily or combinations of the 2 drugs in full or half doses were evaluated in 31 asthmatic outpatients in a double-blind, randomized crossover design. The combination of half doses of the 2 drugs produced slightly better bronchodilation than high-dose, single drug regimen and similar bronchodilation as a high-dose combination. Side effects during half dose combination were less than when theophylline alone or high dose combination treatment were administered. High-dose combination treatment produced slightly more ventricular ectopic beats and supra ventricular ectopic beats, and 3 patients developed cardiac arrhythmias. A combination of half the normally used doses of oral slow-release formulations of terbutaline and theophylline seems superior to a high-dose combination. PMID- 2578975 TI - Effects of inhibiting DNA synthesis with hydroxyurea on stretch-induced skeletal muscle growth. AB - Growth of chicken patagialis muscle in response to passive stretch for 7 days was studied in the absence and presence of the DNA synthesis inhibitor hydroxyurea. In the absence of hydroxyurea, the DNA content and concentration of the stretched muscle increased 101% and 40%, respectively, relative to the unstretched contralateral control. Stretch-induced growth was characterized by large increases in muscle wet weight (56%), protein content (44%), RNA concentration (63%), cross-sectional area (67%), and mean fiber cross-sectional area (50%). In the presence of hydroxyurea, DNA content increased only 22% whereas DNA concentration decreased 11% in response to stretch. However, except for RNA concentration, which increased 84%, stretch-induced growth in the hydroxyurea treated birds exhibited the same characteristics as those in the sham-treated animals. Therefore, the large increase in DNA content and concentration observed after 7 days of stretch-induced growth in the chicken patagialis muscle was not necessary for the growth to occur. PMID- 2578974 TI - Ca++ dependent bistability induced by serotonin in spinal motoneurons. AB - The plateau potential, responsible for the bistable state of spinal motoneurons, recently described in the decerebrate cat, was suggested to depend on serotonin (Hounsgaard et al. 1984). In an in vitro preparation of the spinal cord of the turtle we now show that serotonin, applied directly to the bath, transforms the intrinsic response properties of motoneurons, uncovering a plateau potential and voltage sensitive bistability. The changes induced by serotonin were blocked by Mn++, while the plateau potential and the bistability remained after application of tetrodotoxin. We conclude that serotonin controls the expression of a Ca++ dependent plateau potential in motoneurons. PMID- 2578973 TI - Some properties of ionic channels activated by excitatory amino acids in hippocampal neurons. AB - Properties of excitation induced by various excitatory amino acids were studied in thin slices of the guinea pig hippocampus in the presence of Mn2+, tetrodotoxin and tetraethylammonium chloride. Depolarizations induced by L glutamate (Glu), quisqualate (Quis) and D-homocysteate (DH) were accompanied consistently by decreases in neuron input resistance. In the current-voltage function, increases in input resistance were never observed at any membrane potential. The amplitude of Glu, Quis and DH responses decreased during tonic outward currents and increased during tonic inward currents. Although neuron input resistance decreased with depolarizations induced by L-aspartate (Asp) as well, the magnitude of the resistance reduction was significantly smaller than that induced by Glu. Asp responses changed in amplitude as did Glu responses during tonic inward and outward currents. Depolarizations induced by N-Methyl-D aspartate (NMDA) were accompanied by apparent increases in input resistance, and their amplitudes increased and decreased during tonic depolarization and hyperpolarization, respectively. Mn2+ was almost without effect at the concentration used (2.7 mM) on responses induced by Glu, DH or Asp. These results suggest that Glu, Quis and DH induce depolarizations in hippocampal neurons by activating only Quis receptors, and that Asp activates Quis receptors preferentially though it activates NMDA receptors as well. PMID- 2578976 TI - Are cat lingual muscles dually innervated by the hypoglossal nerve and facial nerve? AB - The origins of the somatic motor nerve innervating the cat lingual muscles were studied using the horseradish peroxidase (HRP) method. Following HRP injection into the lingual muscles, labeled neurons were found not only in the hypoglossal nucleus but also in the facial nucleus, ipsilateral to the injection side. HRP labeled neurons in the facial nucleus were principally observed in the ventromedial and ventrolateral divisions of the nucleus. This study suggests that cat lingual muscles are innervated by both hypoglossal motoneurons and some of the motoneurons in the ventromedial and ventrolateral divisions of the facial nucleus. PMID- 2578977 TI - Characterization of lymphoid and nonlymphoid cells in the white pulp of the spleen using immunohistoperoxidase techniques and enzyme-histochemistry. PMID- 2578978 TI - Intracellular injection of cAMP and cGMP into snail neurones induces an increase in Na+-conductance. AB - Injection of cAMP and more rarely cGMP into the neurones of the snail Helix pomatia induces an increase in membrane conductance, membrane depolarization and excitation. The effect is theophylline-dependent and has a reversal potential near -10mV. PMID- 2578979 TI - Mast cells are present during angiogenesis in the chick extraembryonic vascular system. AB - The extraembryonic vascular membranes of 3-day-18-day chick embryos were examined for the presence of mast cells. As early as 3.5 days mast cells were found on the area vasculosa. It is suggested that these cells have a role in angiogenesis of the chick extraembryonic vascular system. PMID- 2578980 TI - Comparison of diurnal and nocturnal rates of 5-hydroxytryptamine turnover in the rat mediobasal hypothalamus. AB - Rates of 5-hydroxytryptamine (5-HT) turnover in the mediobasal hypothalamus of male rats were estimated using pharmacological methods during the daytime and at night. Concentrations of 5-HT in this hypothalamic area were higher nocturnally than diurnally; this was apparently due to increased 5-HT synthesis and decreased 5-HT catabolism at night. PMID- 2578981 TI - Conformational changes induced by Mg2+ on actin monomers. An immunologic attempt to localize the affected region. AB - The effect of Mg2+ ions on the conformation of G-actin and in particular on the accessibility of its antigenic regions has been tested. Experiments were performed with G-actin coupled to Sepharose 4B which was, therefore, maintained in the monomeric state. The results presented her show that the 2mM MgCl2 perturbed antigenic site is located in a central region of the actin sequence. PMID- 2578982 TI - Association of the glucocorticoid hormone receptor with ribonucleic acid. AB - The hypothesis that the glucocorticoid hormone receptor interacts with RNA has been tested in cultured rat hepatoma cells. The receptor was covalently labeled with radioactive dexamethasone mesylate, and putative RNA-receptor complexes were stabilized by either cell-free crosslinking using formaldehyde or irradiation of intact cells. After chemical cross-linking in vitro, the receptor displayed the buoyant density of a ribonucleoprotein in CsCl gradients. After photochemical crosslinking in cells labeled with radioactive uridine, the receptor analysed by polyacrylamide gel electrophoresis was carrying labeled ribonucleotides. PMID- 2578983 TI - The carbohydrate moiety of aminopeptidase N of rabbit intestinal brush-border membrane. AB - Endoglycosidase F was used to eliminate the N-linked complex glycans from intestinal aminopeptidase N. The glycans which were probably O-linked remaining after the endoglycosidase F treatment exhibited the human blood group A and H determinants expressed in enzymes from A+ or A- rabbits, respectively. The molecular mass estimation of the two types of glycans by SDS-polyacrylamide gel electrophoresis and the sugar composition of aminopeptidase from A+ and A- rabbits strongly suggested the presence of eight N-linked complex glycans and two O-linked oligosaccharides bearing the human group antigenicity. PMID- 2578984 TI - alpha-MSH and neurofilament M-protein share a continuous epitope but not extended sequences. An explanation for neurofibrillary staining with alpha-MSH antibodies. AB - The long recognized neurofibrillary immunoreactivity of the nervous system with alpha-MSH antibodies arises from an epitope on neurofilament M-protein which we have now characterized. It is situated in the amino terminal residues where M protein and alpha-MSH exhibit similar but not identical sequences. Their divergence past residue 5 precludes a physiological significance of the crossreactivity which seems to have arisen fortuitously. Our results question previous speculations as to the existence of extrapituitary alpha-MSH-like hormones. PMID- 2578985 TI - The effect of GTP hydrolysis and transpeptidation on the arrangement of aminoacyl tRNA at the A-site of Escherichia coli 70 S ribosomes. AB - From the affinity labelling of 70 S ribosomes with a photoreactive derivative of Phe-tRNAPhe bearing an arylazido group on guanine residues, it has been found that different sets of ribosomal proteins are labelled in the course of three successive steps of EF-Tu-dependent binding of aminoacyl-tRNA derivative at the A site. Proteins S5, S7, S8, S16, S17, L9, L14, L15 and L24 were labelled before GTP hydrolysis; proteins S5, S7, S9, S11, S14, S18, S19, S21, L9, L21 and L29- after GTP hydrolysis; proteins S2, S5, S7, S21, L11 and L23--after GTP hydrolysis and transpeptidation. PMID- 2578986 TI - Gene expression in the polycistronic operons of Escherichia coli heat-labile toxin and cholera toxin: a new model of translational control. AB - A new model is proposed based on the suggestion that stable local secondary structures of mRNA interfere with ribosome movement on mRNA and consequently reduce the translation rate. This model accounts for a different level of translation for each cistron in the polycistronic mRNA of Escherichia coli heat labile toxin (LT) and cholera toxin. We also conclude that the mRNA secondary structures have been conserved during the evolution of the toxin genes for its functional importance. PMID- 2578987 TI - Is the transient nature of the secretory response of chromaffin cells due to inactivation of calcium channels? AB - Catecholamine release from chromaffin cells in response to carbamylcholine and high K+ is transient. Monitoring intracellular free calcium ([Ca2+]i) using quin2 demonstrated a transient rise in [Ca2+]i in response to carbamylcholine. The termination of secretion due to carbamylcholine is probably a consequence of the return of [Ca2+]i to resting levels as the nicotinic receptors desensitise. Depolarisation with 55 mM K+ led to a long-lasting rise in [Ca2+]i which persisted after the secretory response had terminated. The maintained rise in [Ca2+]i appeared to be due to continued opening of verapamil-sensitive Ca2+ channels. These results suggest that inactivation of voltage-dependent Ca2+ channels does not account for the transient nature of the secretory response in chromaffin cells. PMID- 2578988 TI - Rat plasma alpha 1-inhibitor3: a member of the alpha-macroglobulin family. AB - The overall mechanism of interaction with proteinases of alpha 1-inhibitor3, a plasma proteinase inhibitor so far specific to the rat, has been shown to be closely similar to that described for alpha-macroglobulins. This mechanism includes: (i) the cleavage of at least one susceptible peptidic bond which leads to structural changes in the molecule. (ii) The cleavage of a putative thiol ester bond in another site of the molecule which permits the covalent linkage of the enzyme. Moreover, fragmentation of alpha 1-inhibitor3 upon heating as observed for alpha-macroglobulin quarter subunits has been demonstrated. The question is raised of the presence of such a molecule in rat plasma in addition to two alpha-macroglobulin species, all of these proteinase inhibitors being antigenically unrelated. PMID- 2578989 TI - Citrate synthase: an immunochemical investigation of interspecies diversity. AB - Rabbit antibodies have been raised to pig heart citrate synthase. Using purified IgG, competitive enzyme-linked immunoassays and assays of citrate synthase activity indicate the presence of antibodies to a number of antigenic sites on the enzyme, only some of which are essential for catalytic activity. From a comparison of citrate synthases from prokaryotic and eukaryotic organisms, the degree of interaction between antibody and enzyme was in the order: pig heart greater than pigeon breast greater than Bacillus megaterium greater than Escherichia coli. These findings are discussed in terms of the known interspecies diversity of the enzyme. PMID- 2578990 TI - The narcotic antagonist naltrexone has a biphasic effect on the nicotinic acetylcholine receptor. AB - It is known that narcotic antagonists interact with many cholinergic pathways but less in known about specific mechanisms. Using neonatal rat myoballs to study single channel behaviour of the acetylcholinegated nicotinic receptor, it was found that micromolar concentrations of naltrexone had no effect on channel conductance but caused open channel blockade by increasing the flickering from the open to the closed state in a concentration-dependent manner. At micromolar concentrations of naltrexone, the frequency of channel opening was decreased and bursts were grouped in clusters, whereas at nanomolar levels the frequency of opening was increased. The sequential model for ion-channel blockade cannot explain these effects, and an alternative allosteric mechanism of action is proposed. PMID- 2578991 TI - Human tissue-type plasminogen activator is related to albumin and alpha fetoprotein. AB - Using a computer program designed to detect evolutionary relationships between proteins, I find that residues 72-110 of the mature sequence of human tissue-type plasminogen activator (t-PA) and 39 residues at the carboxy terminus of human albumin have a comparison score that is 8.8 standard deviation units higher than that obtained with a comparison of randomized sequences of these proteins. The probability (p) of getting this score by chance is approximately 10(-18), indicating that part of t-PA and albumin are derived from a common ancestor. I also find that alpha-fetoprotein, a relative of albumin is related to t-PA. Part of this region on t-PA has been previously shown to be related to epidermal growth factor. t-PA, albumin, alpha-fetoprotein, and epidermal growth factor have diverse biological activities. The finding that these proteins are related suggests some new approaches for studying their functions. PMID- 2578993 TI - Major transcripts containing B1 and B2 repetitive sequences in cytoplasmic poly(A)+RNA from mouse tissues. AB - The cytoplasmic poly(A)+RNAs containing ubiquitous B1 and B2 repeats of the mouse genome in normal tissues and tumors have been studied. Only one strand of the repeats is represented in cytoplasmic RNA in all the cases. Some tumor cells were found to be enriched in 1.4 kb B1+mRNA, 1.6 kb B2+mRNA and small (0.2-04 kb) B1+ and B2+ poly(A)+RNAs. On the other hand, mouse liver and kidney contained high amounts of 2 kb B2+mRNA. Its content increased noticeably in the regenerating liver, but in hepatoma it dropped to a zero level. Thus, the switching on (or off) of B1- and B2-containing mRNAs occurred noncoordinately. At the same time, the activation of the synthesis of small B2+RNA and small B1+RNA was simultaneous. PMID- 2578994 TI - Parameters of nursing practice. PMID- 2578992 TI - Major acute phase alpha 1-protein of the rat is homologous to bovine kininogen and contains the sequence for bradykinin: its synthesis is regulated at the mRNA level. AB - The complete amino acid sequence of major acute phase alpha 1-protein of the rat (MAP) was derived from the nucleotide sequence of cloned cDNA. Amino acid analysis and partial sequencing supported the predicted sequence. The amino acid compositions of MAP and rat low-Mr kininogen are identical within experimental variation. The sequence is homologous (60%) to that of bovine low-Mr kininogen and both proteins carry the sequence for the vasoactive nonapeptide bradykinin in their C-terminal region. The rate of synthesis of MAP and the levels of MAP mRNA change coordinately during the acute phase response to inflammation. PMID- 2578995 TI - [Possible role of the molecular characteristics of sodium channel inactivation system of the nerve fiber in impulse coding]. AB - A Hodgkin-Huxley type mathematical model of the Ranvier node aided to reveal interconnections between molecular characteristics of the sodium channels inactivation system (h-system) and impulse coding. Analysis of the second order properties of the system permitted to describe its energy profile, effective charge magnitudes and to suggest that in sensory fibres main part of the effective charge transfer occurs between the open and the first closed states whereas in motor fibres it occurs between the neighbouring closed states. PMID- 2578996 TI - Monoclonal antibody to intermediate filaments of cytokeratin type. I. Drug studies and reactivity with cultured cells and tissue sections. AB - Establishment of a mouse-mouse hybridoma and partial characterization of IgM monoclonal antibody (M-04) identifying cytoplasmic filamentous structures is described. Immunofluorescence performed on a panel of various cultured human cell types as well as on frozen sections of normal and tumour tissues revealed specificity of M-04 antibody for cells of epithelial origin. Using MCF-7 cell line as a model, staining patterns of microtubules, microfilaments and M-04 target filaments in untreated cells were compared with those pretreated with Colcemid and Cytochalasin B. From both differential staining of various cell types and the results of drug studies it is concluded that monoclonal antibody M 04 binds to intermediate filaments of cytokeratin type. Furthermore, restricted expression of M-04 target determinant among epithelial tissues is suggested from the lack of reaction in stratified skin epithelium. PMID- 2578997 TI - Modulation of the effects of cyclophosphamide on the lymphoid system of mice by double-stranded RNA. AB - The ds RNA, an inducer of interferon, displayed a marked modulatory action on damage induced in the lymphoid system of mice by a single injection of cyclophosphamide. Its action depended on the type of lymphoid tissue and on the time interval between injection of ds RNA and CY. The "unwanted" synergy between the action of ds RNA and CY was most pronounced in the thymus in which a further great decrease in weight and cellularity was observed at all time intervals. In the case of the spleen and lymph nodes, the undesirable synergy was manifest only when the ds RNA was injected prior to CY. Simultaneous injection of ds RNA and CY, or injection of ds RNA after CY, had beneficial effects on the weight and cellularity of lymphoid organs, possibly by accelerating the regeneration processes. PMID- 2578998 TI - Discover the versatility of dental office video. PMID- 2578999 TI - Expression of keratins and other cytoskeletal proteins in mouse mammary epithelium during the normal developmental cycle and primary culture. AB - Mammary epithelium is composed of ductal, alveolar, and myoepithelial cells, and undergoes dramatic responses in growth, differentiation, and function to hormonal stimuli during the four stages of the mammary developmental cycle represented in virgin, pregnant, lactating, and involuting animals. To determine if progression of the epithelium through the cycle is accompanied by changes in cytoskeletal composition, particularly the keratins, the polypeptides in cytoskeletal extracts from BALB/c mouse mammary tissues were analyzed by one- and two-dimensional gel electrophoresis combined with immunoblots using polyclonal and monoclonal antikeratin antibodies. The major polypeptides in cytoskeletal fractions enriched in intermediate filaments included seven acidic and three basic components ranging in molecular weight from 40,000 to 90,000. Two major polypeptides of Mr 50,000 and 40,000, along with two minor components of Mr 57,000 and 55,000 were identified as keratins. The polypeptide profiles of mammary glands from virgin, pregnant, lactating, and involuting mice were very similar, indicating a remarkable stability of cytoskeletal composition during hormonal shifts and periods of minimal or maximal cell growth and differentiated function. The data also suggest that ductal and alveolar cells express the same set of cytoskeletal polypeptides, including keratins. Mammary cells grown in primary culture exhibited a loss or reduction in most of the basic polypeptides, a large increase in an acidic Mr 55,000 keratin, and the appearance of a prominent acidic polypeptide of Mr 46,000. The latter results demonstrate that keratin expression in mouse mammary epithelial cells is subject to regulation by certain environmental factors. PMID- 2579000 TI - Patterns of ionic current through Drosophila follicles and eggs. AB - Large steady electrical currents traverse Drosophila follicles in vitro as well as permeabilized eggs. During the period of main follicle growth (stages 9-11), these currents enter the anterior or nurse cell end of the follicles. This inward current acts like a sodium ion influx with some calcium involvement. During the period of chorion formation (stages 12-14), foci of inward current also appear at the posterior, posterodorsal, and anterodorsal regions of follicles in vitro. In stage 14, the posterior in current acts like a chloride ion efflux. In preblastoderm eggs substantial currents continue to enter their anterior end; while weaker and less frequent ones enter their posterior end. We present models in which the currents during follicle growth are driven by the plasma membrane of the oocyte nurse cell syncitium; the external currents during choriogenesis are driven by the follicular epithelium; while the currents through the preblastoderm egg are driven by its plasma membrane. Measurements of pole-to-pole resistances and voltages across preblastoderm eggs indicate that the transcellular currents normally maintain a steady extracellular voltage gradient along the perivitelline space, with the anterior pole kept negative by perhaps 4 or 5 mV. The developmental significance of these currents is discussed. PMID- 2579001 TI - Two-stage hormonal control of type IV collagen mRNA levels during differentiation of F9 teratocarcinoma cells. AB - A cDNA clone related to mouse Type IV collagen has been prepared from F9 teratocarcinoma cells induced to differentiate with retinoic acid and dibutyryl cAMP. This cDNA clone has been used to investigate the regulation of Type IV collagen mRNA during differentiation. The level of this mRNA is very low in untreated F9 cells, increases substantially after treatment of the cells with retinoic acid, and is further increased by addition of dibutyryl-cAMP. In contrast, dibutyryl-cAMP has no effect on the mRNA level in cells that have not been previously exposed to retinoic acid. These results demonstrate that these two compounds regulate in a sequential manner the steady-state level of Type IV collagen mRNA. This cDNA clone should allow a detailed examination of the mechanism of the two-stage regulation of collagen expression by retinoids and cyclic AMP. PMID- 2579002 TI - Nerve growth factor changes the relative levels of neuropeptides in developing sensory and sympathetic ganglia of the chick embryo. AB - The effects of chronic nerve growth factor administration on the development of neuropeptides in the embryonic chick peripheral nervous system were quantitated by radioimmunoassays. Starting at embryonic Day 3.5, daily doses of 20 micrograms of nerve growth factor (NGF) increased the substance P content of lumbosacral spinal sensory ganglia at all ages studied (Days 10-14), while having no effect on substance P levels of thoracic sensory ganglia. In contrast, the contents of somatostatin were increased in both thoracic and lumbosacral ganglia, but only at comparatively late time points (Day 14). Nerve growth factor administration was also found to decrease the somatostatin contents of lumbosacral paravertebral sympathetic ganglia at early time points (Day 8) while increasing levels at later stages (Day 14), thus acting to accelerate the normally occurring developmental changes in level of this peptide. These changes were shown to be specific for somatostatin by demonstrating that NGF increased tyrosine hydroxylase levels in sympathetic neurons at Day 8, and had no effect on sympathetic vasoactive intestinal polypeptide levels at Day 14. It has been concluded that exogenous NGF does not simply act to increase or prolong the expression of neuron-specific phenotypes in the chick, but rather its action is time and location dependent to accelerate development. PMID- 2579003 TI - Assay for islet cell antibodies. Protein A--monoclonal antibody method. AB - Assays for islet cell antibodies (ICA) are finding increasing application in clinical diabetology. We have developed a new islet cell antibody assay system (ICA-pA), whose salient features include: (1) utilization of fluorescein conjugated staphylococcal protein A as a standard second-step reagent, the advantages of this approach being improved "signal" (islet)/"noise" (acini) ratio due to reduction of interfering background acinar pancreatic staining, and facilitation of assay standardization provided by the use of a chemically pure conjugated protein A reagent; (2) monoclonal antibody counterstaining with rhodamine-conjugated BISL-32 for the rapid identification of islets in pancreatic sections; and (3) quantitation of circulating serum ICA by microimmunofluorometric techniques. PMID- 2579004 TI - Albumin permeation of new vessels is increased in diabetic rats. AB - 125I-bovine serum albumin (BSA) permeation of the vasculature of 3-wk-old granulation tissue (induced by subcutaneous implantation of polyester fabric) formed in the diabetic milieu was assessed in female BB/W, spontaneously diabetic rats and in male, Sprague-Dawley rats with streptozocin-induced diabetes as well as in corresponding nondiabetic controls. Albumin permeation of new granulation tissue vessels was markedly increased in both groups of diabetic animals relative to that of nondiabetic controls, while albumin permeation of vessels in most other tissues did not differ for controls and diabetics. These observations indicate that the functional integrity of new vessels formed in the diabetic milieu is impaired: (1) to a greater extent than that of older vessels formed before induction of diabetes and (2) relative to new vessels in nondiabetics. The implication of these observations is that molecular constituents of vessels synthesized in the diabetic milieu are quantitatively and/or qualitatively abnormal and/or their incorporation into vessels is defective. PMID- 2579006 TI - Augmentation of keratinized gingiva. PMID- 2579005 TI - Carbohydrate antigen defined by a monoclonal antibody raised against a gastric cancer xenograft. AB - A monoclonal antibody, ST-4-39, was obtained by using a human gastric cancer xenograft, St-4, as an immunogen. Immunization was achieved by transferring immunocompetent mouse spleen cells into a nude mouse bearing St-4. Hybridomas were produced with the spleen cells of the mouse after rejection of the tumor and screened for immunohistochemical reactivity with cancers and normal tissues on formalin-fixed paraffin sections. ST-4-39 immunohistochemically reacted with various cancers including gastric, colorectal and pancreatic cancers as well as some normal tissues. ST-4-39 and NS 19-9 differed in immunohistochemical reactivity, although they reacted with some cancers and a few normal tissues in common. PBS extracts of normal and cancer tissues were examined for antigen reactive with ST-4-39 by sandwich enzyme immunoassay. Extractable antigen was detected in adenocarcinomas of colon, stomach and lung, while it was detected only in salivary gland and trachea among normal tissues examined. Gel filtration analysis of the antigen indicated a molecular weight of greater than or equal to 1 X 10(6), and the antigenic determinant was suggested to be a carbohydrate chain with terminal sialic acid by studies using periodic acid, neuraminidase and pronase treatments. Furthermore, the ST-4-39 antigen affinity-purified from two gastric cancer strains was shown to contain multiple carbohydrate determinants including sialyl-Lewisa and sialyl-Lewisx, suggesting the antigen to be a mucin. PMID- 2579007 TI - Cisplatin, vinblastine, and bleomycin therapy of yolk sac (endodermal sinus) tumor of the ovary. AB - Five patients with yolk sac (endodermal sinus) tumor of the ovary were treated with cisplatin, vinblastine, and bleomycin combination therapy (PVB). Four of five achieved a complete remission and remain free from disease 24 to 53 months from start of PVB therapy. One patient did not respond well to PVB and died 11 months after start of PVB therapy. One patient who was treated with PVB after unilateral salpingo-oophorectomy has delivered a normal term infant. Serum alpha fetoprotein levels were monitored in all patients during and after therapy. Serum alpha-fetoprotein was correlated with clinical course. PMID- 2579008 TI - Pure dysgerminoma of the ovary with elevated serum human chorionic gonadotropin: diagnostic and therapeutic considerations. AB - Pure ovarian dysgerminomas with associated elevation of human chorionic gonadotropin (hCG) are rare, and their optimum management is unclear. We report here a 24-year-old woman with stage III dysgerminoma of the ovaries, with bulky intrapelvic disease, paraaortic adenopathy, and elevated pre- and postsurgical serum beta-hCG titers. Following administration of whole abdominal-pelvic and mediastinal irradiation therapy, the patient's adenopathy regressed, her serial beta-hCG titers returned to normal, and she has remained free of disease for the past 30 months. Histopathological studies revealed a pure dysgerminoma with scattered giant cells which were negative for hCG by immunoperoxidase staining. The literature is reviewed with reference to the significance of elevated hCG levels, the presence of giant cells in association with dysgerminoma of the ovary, and therapeutic implications. Serial determinations of beta-hCG titers may prove to be as valuable in the management of these patients as they are in patients with testicular tumors. PMID- 2579009 TI - Modified VAB-3 combination chemotherapy of advanced and recurrent endodermal sinus tumors of the ovary. AB - Three patients with advanced and recurrent endodermal sinus tumor (EST) of the ovary were treated with modified vinblastine, actinomycin-D, and bleomycin (VAB 3) regimen. Serum alpha-fetoprotein (AFP) levels were monitored for all patients during and after therapy. In all patients a clinical response was achieved. In one stage IV patient with huge multiple liver metastases complete response was attained and she is free of disease following secondlook larparotomy. In other two patients, one stage IV and another recurrent, with large liver metastases, partial responses were achieved with normalization of serum AFP. Serum AFP monitoring is valuable for the management of EST, but a negative AFP titer does not eliminate the possibility of persistent or recurrent disease. The VAB-3 combination, previously found effective in metastatic nonseminomatous testicular cancer, is also effective in advanced and recurrent EST of the ovary. PMID- 2579011 TI - [Early detection of perinatal complications. Physiology and pathophysiology of alpha-1-fetoprotein in pregnancy]. PMID- 2579010 TI - Bleomycin, vincristine, mitomycin-C, and cisplatin in the management of gynecological squamous cell carcinomas. AB - Twenty-one patients with squamous carcinoma of the genital tract were treated with bleomycin, Oncovin, mitomycin-C, and cisplatin (BOMP). Six patients received BOMP as primary therapy. Five of six responded with one patient having an autopsy proven complete response after treatment for a disseminated adenosquamous carcinoma. Eight patients were treated for early recurrence, none responded. Seven patients were treated for late recurrences and one responded. We believe that BOMP has significant potential for primary treatment, but not for early or late recurrent disease. PMID- 2579012 TI - A clinical perspective on the role of neurotransmitters in mental disorders. AB - The authors first review the mechanisms of neural transmission. They then provide a detailed discussion of norepinephrine, dopamine, and serotonin--the three neurotransmitters that have been implicated most often in etiological studies of affective disorders and schizophrenia. After outlining the synthesis, location, and pharmacological response of these transmitters, the authors consider the role of neurotransmission in the theoretical models of depression and schizophrenia. PMID- 2579013 TI - Lipomatous tumors: a correlative cytologic and histologic study of 27 tumors examined by fine needle aspiration cytology. AB - A correlative cytologic and histologic study of 12 benign lipomatous tumors and 15 liposarcomas (well-differentiated, myxoid, round cell, and pleomorphic) is presented. In two cases the fine needle aspiration material was embedded in Epon for light and electron microscopic examination. Good correlation was found between the histologic and cytologic findings in the fine needle aspiration material. Pitfalls in the cytologic diagnosis of regressively changed lipoma, intramuscular lipoma, angiolipoma, hibernoma, and lipoblastoma, which may lead to an erroneous diagnosis of liposarcoma, are illustrated. The cytologic appearances of the liposarcomas varied with histologic type, although in all of these tumors the main criterion was the presence of atypical multivacuolated lipoblasts with characteristically scalloped nuclei. Staining of the aspirated material with Alcian blue at varying pH levels for characterization of the glycosaminoglycan content may help in the distinction of myxoid liposarcomas from myxoid chondromatous tumors and chordomas. May-Grunewald-Giemsa staining is considered the most useful staining method, while fat staining is considered of limited or no value in the cytologic diagnosis of lipomatous tumors. Epon embedding of fine needle aspirates for light and electron microscopic examination seems to be a useful diagnostic technique. PMID- 2579014 TI - Histochemical and morphologic studies of mucosa bordering rectosigmoid carcinomas: comparisons with normal, diseased, and malignant colonic epithelium. AB - Surgically obtained rectosigmoid mucosa ("transitional" mucosa, TM) adjacent to eight primary carcinomas was compared with diseased mucosa (DM) from eight patients without primary carcinoma and mucosa from two normal control subjects by mucin histochemical and morphologic techniques. No differences were found between TM and DM that might have suggested premalignant changes unique to TM. An excess of sialidase-susceptible sialomucins was found in both TM and DM, as was loss of the sulfomucin-sialomucin gradient usually found between normal crypts and surface cells. Increased sialic acid in TM and DM may represent a nonspecific response to injury or inflammation and has been found in other epithelia under similar circumstances. Sialidase also induced substantial reduction of periodic acid-Schiff (PAS) staining, probably due to loss of sialic acid since no other sugars were released during sialidase digestion, as determined by thin-layer chromatography analysis of post-digestion supernatants. Carcinomas generally showed more staining with PAS than with basic dyes; PAS staining was minimally reduced by diastase and sialidase but markedly reduced by phenylhydrazine interposition, suggesting that some type of neutral glycoprotein was responsible. Finally, it was found that overreliance on the high-iron diamine-Alcian blue technique as a single procedure is unwise; this procedure should be accompanied by the use of singly applied dyes, especially high-iron diamine, together with other enzymatic and staining procedures. PMID- 2579015 TI - Multicentric angiofollicular lymph node hyperplasia: a clinicopathologic study of 16 cases. AB - A clinicopathologic analysis of 16 cases of multicentric angiofollicular lymph node hyperplasia (MAFH) was performed. Histologically, the disease was characterized by recognizable lymph node architecture that was at least partially intact, by paracortical hyperplasia with prominent vascular proliferation, and by numerous evenly distributed, apparently benign germinal centers of various types, usually including some typical hyaline-vascular centers. At the onset of the disease, 12 patients had the plasma cell (PC) type of MAFH, three patients had the hyaline-vascular (HV) type, and one patient presented with PC and HV types at separate sites. Transitions between the PC and HV types were observed in two cases. Immunologic studies demonstrated polyclonal populations of plasma cells in the lymph nodes of all patients and the absence of suppressor T lymphocytes in the one patient tested. Clinically, the patients had constitutional symptoms, multicentric lymphadenopathy, hepatosplenomegaly in many cases, and abnormal laboratory findings, including anemia, polyclonal hypergammaglobulinemia, and bone marrow plasmacytosis. The 16 patients were placed in four different clinical groups based on presentation and course: stable disease, chronic relapsing disease, aggressive disease, and development of malignant lymphoma. Ten of the 16 patients died (median survival, 26 months; range, eight to 170 months). Multicentric angiofollicular lymph node hyperplasia appears to be a variant of classic angiofollicular lymph node hyperplasia (Castleman's disease) and is associated with significant morbidity and mortality. PMID- 2579016 TI - Congo red-negative amyloidosis-like glomerulopathy. AB - Three cases of amyloidosis-like glomerulopathy are presented in which renal amyloidosis was initially diagnosed on the basis of ultrastructural findings, despite negative Congo red staining. The histologic and immunofluorescence findings and, on careful examination, ultrastructural features of this amyloidosis-like glomerulopathy all serve to distinguish it from true amyloidosis. The clinical behavior suggests that it is a primary glomerulopathy since, with time, no other systems become involved. PMID- 2579018 TI - S-100 protein immunostaining in the differential diagnosis of chondroblastoma. AB - In an effort to investigate the utility of immunostaining for S-100 protein in the differential diagnosis of chondroblastoma, the expression of S-100 protein in nine chondroblastomas was compared with that in six giant cell tumors, six aneurysmal bone cysts, four giant cell reparative granulomas, six cases of fibrous dysplasia, two cases of osteitis fibrosa cystica, two nonossifying fibromas, and one clear cell chondrosarcoma. Five enchondromas, three typical chondrosarcomas, and one mesenchymal chondrosarcoma were also included as control tumors. The proliferating stromal cells in seven of the nine chondroblastomas stained for S-100 protein, as did the lacunar chondrocytes in all of the enchondromas and chondrosarcomas and rare stromal cells in the clear cell chondrosarcoma. In contrast, none of the other tumefactive bone lesions included in this study demonstrated S-100 protein immunoreactivity. These results suggest that immunohistochemical assessment of S-100 protein may be a method for diagnostically separating chondroblastoma from pathologic entities that could be histologically confused with it in the presence of limited biopsy material. However, clear cell chondrosarcoma would appear to represent an exception to this general statement. PMID- 2579017 TI - Pregnancy-associated plasma protein A: a clinically significant predictor of early recurrence in stage II breast carcinoma. AB - The primary tumors and metastases from 30 patients with stage II breast carcinoma treated with low- or standard-dose combination chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil) were studied by the immunoperoxidase technique for pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific beta-1 glycoprotein (SP-1), and placental protein five (PP-5). In addition to immunostaining, 25 traditional clinicopathologic features were assessed with respect to early (at less than two years) recurrence. Of the 11 patients with early recurrences, nine (82 per cent) were PAPP-A-positive, while 16 of the 19 patients without early recurrences (84 per cent) were PAPP-A-negative (P less than 0.0005). None of the other clinicopathologic features correlated with early recurrence. Immunostaining for PAPP-A is thus a clinically significant predictor of early recurrence in patients with stage II breast carcinoma. PMID- 2579019 TI - Intercellular NOR-Ag-variability in man. II. Search for determining factors, clonal analysis. AB - Intercellular, nonartifactual variability of nucleolar organizer region (NOR)-Ag staining was studied in cultured human peripheral blood lymphocytes, skin and embryonic fibroblasts. No differences in number and character of variable NORs and intensity of their staining were observed between lymphocytes stimulated to proliferate with phytohemagglutinin and pokeweed mitogen, as well as lymphocytes of first- and second division. The number of NOR associations per cell and the number of associated chromosomes per association were also similar. In a given individual these criteria were similar in lymphocytes and fibroblasts. In all nine clones derived from three independent parental fibroblast cultures the intercellular NOR-Ag-variability was similar to that observed in a given parental cell line. A significant decrease in the number of metaphases containing NOR associations was observed in second-division lymphocytes compared with first division ones, as well as in skin fibroblasts compared with lymphocytes. PMID- 2579020 TI - Mycobacterial antigen-specific human T-cell clones secreting macrophage activating factors. AB - Macrophage activating factor (MAF) is produced by antigen-stimulated lymphocytes and activates macrophages for antimicrobial function. The capacity of individual microbial antigens to evoke and regulate this response has been explored using an affinity purified antigen (TB68) of Mycobacterium tuberculosis in combination with T-cell cloning. Four helper/inducer clones are described which responded strongly to this antigen. Three were specific, proliferating only to TB68 antigen and antigenic preparations containing this antigen. However, one of these clones (68.1) did not proliferate to BCG and PPD which contained the TB68 antigen. In addition, another clone, 68.13, also proliferated to other antigenic preparations which did not contain the TB68 antigen. Taken together, these data indicate the presence of several epitopes in the affinity-purified TB68 antigen. All the clones produced MAF, which enhanced H2O2 production in U937 cell lines and conventional macrophages matured from monocytes. Thus, T-cell clones proliferating to a mycobacterial antigen constitutively secrete lymphokines that activate macrophages to antimicrobial immunity. PMID- 2579021 TI - The functional association of Lyt antigens with lymphokine production. AB - The effects of anti-Lyt antibodies on secretion of lymphotoxin, macrophage activating factor and interferon were studied. Anti-Lyt-1 antibodies added to primary mixed lymphocyte reactions (MLR) significantly enhanced lymphokine secretion, whereas anti-Lyt-2 antibodies had no effect in primary responses. However, when added to secondary MLR, anti-Lyt-1 antibodies manifested moderate enhancing effect on lymphokine levels, whereas anti-Lyt-2 antibodies markedly reduced lymphokine secretion. These results suggested that T cells of different subsets produced lymphokines during primary and secondary responses. The Lyt phenotype of T cells involved in lymphokine secretion and the effects of anti-Lyt antibodies on selected T-cell subsets were therefore studied. It was demonstrated that the majority of lymphokine producing cells during primary MLR reside within the Lyt-1+2- population, which was potentiated by anti-Lyt-1 antibodies, but unaffected by anti-Lyt-2 antibodies. However, during secondary MLR, a considerable proportion of lymphokines was produced by the Lyt-1-2+ population, which was blocked by anti-Lyt-2 antibodies. Lymphokine production induced by concanavalin A, in contrast to that induced by alloantigens, was unaffected by anti-Lyt-2 antibodies. The implication of these results on the role of Lyt molecules in T-cell functions is discussed. PMID- 2579022 TI - Effects of low doses of cyclophosphamide and low doses of irradiation on the regulation of induced erythrocyte autoantibodies in mice. AB - This paper describes some of the characteristics of a suppressor cell which is capable of regulating a rat RBC-induced autoantibody response against mouse RBCs. This cell, which appears to function as an inducer of suppression on transfer to naive recipients, is sensitive to low doses of cyclophosphamide, and its generation is affected by low doses of irradiation. However, the recipients of these cells are insensitive to cyclophosphamide treatment, suppression still being induced in such animals. PMID- 2579023 TI - Identification with monoclonal antibodies of different regions of human plasma fibronectin, including that which interacts with human monocyte fibronectin receptors. AB - The determinant specificities of five monoclonal anti-fibronectin antibodies, designated BC7, CE9, BD4, AB3 and CPG1, were defined and mapped within intact human plasma fibronectin by immunoblot analyses with defined fragments of fibronectin. The latter were derived by tryptic, chymotryptic or cathepsin D digestion of the intact molecule and fractionated by DE-cellulose chromatography and gelatin and/or heparin affinity chromatography. Monoclonal BC7 recognizes intrachain disulphide-formed determinants within the 27,000 MW N-terminal domain; monoclonal CE9 recognizes determinants within an 18,000 MW fragment immediately adjacent to the carboxyl end of the gelatin-binding domain; monoclonal BD4 recognizes determinants within the cell-adhesive domain and within 150,000 of the N-terminus; monoclonal AB3 recognizes intrachain disulphide-formed determinants within 35,000 of the COOH-terminus of the intact molecule and detectable only on the alpha-chain polypeptide subunit; and monoclonal CPG1 recognizes determinants present on both chains of the intact molecule and immediately adjacent to the interchain disulphide bonds at the COOH-terminus. None of the epitopes recognized by these monoclonal antibodies is present at alternative regions of the intact molecule. Fab fragments of each of these monoclonal antibodies were incubated with gelatin-coated sheep erythrocytes which had been reacted with a fixed amount of intact plasma fibronectin. When these target particles were incubated with monolayers of human monocytes and the resultant rosettes were quantitated, the Fab fragments of BD4 markedly inhibited the proportion of monocytes binding these fibronectin-bearing targets, whereas none of the other Fab fragments had an inhibitory effect. Thus, monocyte fibronectin receptors which mediate adherence of fibronectin bridges to a target via gelatin recognize regions within the cell adhesive domains of intact fibronectin but not regions at the amino or carboxy terminals. PMID- 2579024 TI - Antigenic determinants of human thyroglobulin differentiated using antigen fragments. AB - Human thyroglobulin (Tg) was digested with V8 protease and the fragments separated by high performance liquid chromatography (HPLC). The antigenic relationship of the fragments was investigated using mouse monoclonal antibodies to human Tg. The binding of Hashimoto's disease autoantibodies to the fragments was measured by radioimmunoassay. This demonstrated that a minority of the patients recognize an epitope on Tg which others do not. The epitopes identified by the autoantibodies were substantially destroyed in the smaller fragments tested, but these smaller fragments were more efficient stimulators of Tg specific T-cell lines than the larger fragments which carry the antibody binding determinants. This suggests that the parts of the Tg molecule which stimulate autoimmune B cells differ from those which stimulate T cells. PMID- 2579026 TI - The control of the contact sensitivity skin reaction: T-suppressor afferent cell blocks the production of antigen-specific T-helper factor. AB - Lymph node cells from mice painted with the contact sensitizers picryl chloride or oxazolone produce antigen-specific T-helper factor. This is detected by its ability to increase the contact sensitivity response to the injection of small numbers of haptenized spleen cells into the footpads of naive recipients. The production of this T-helper factor is inhibited by the injection of spleen cells from mice given water-soluble, chemically reactive hapten such as picrylsulphonic (trinitrobenzenesulphonic) acid--an agent which induces unresponsiveness. The cells which inhibit the production of T-helper factor are antigen-specific T suppressor cells. They are sensitive to cyclophosphamide given before the injection of picrylsulphonic acid, but are unaffected by adult thymectomy. In this respect, they resemble the family of Ts-aff which inhibit the development of contact sensitivity, specific antigen-induced lymph node proliferation and the specific IgG response, and differ from the T-suppressor efferent cell (Ts-eff) which acts at the expression stage of the contact sensitivity reaction. These results are fully compatible with the view that the Ts-aff inhibits the development of contact sensitivity by blocking the production of antigen-specific T-helper factor. PMID- 2579025 TI - Autoreactive T-cell lines specific for mouse thyroglobulin. AB - Autoreactive T-cell specific for mouse thyroglobulin have been established and characterized. These Lyt 1+ T cells proliferated specifically in response to thyroglobulin presented by syngeneic irradiated spleen cells. The antigen presenting cell requirements of these autoreactive T cells appeared to be the same as those for foreign antigen (PPD) reactive T cells. All lines tested required antigen-presenting cells compatible at the I-A subregion of the H-2 complex. Both T-cell types responded to antigen presented by peritoneal cells and splenic dendritic cells, but only gave optimal responses when whole spleen cells were used. The cross-reactivity patterns of responses to mouse, rat, pig and human thyroglobulins indicated that at least two different epitopes could be recognized by the autoreactive T cells. Furthermore, these epitopes appeared to be different from those recognized by the majority of serum autoantibodies to mouse thyroglobulin. PMID- 2579027 TI - Antigenic variation in clones of Trypanosoma brucei grown in immune-deficient mice. AB - We have produced monoclonal antibodies against six variant surface glycoproteins from early variant antigen types (VATs) of the IsTaR 1 serodeme of Trypanosoma brucei brucei. We have used these in fixed cell immunofluorescence assays to follow the VAT composition of populations of each early VAT when passaged through irradiated mice. The IsTat 1.A and 1.7a populations were stable for more than 30 days (approximately 150 generations), but 1.1a, 1.3a, 1.5a, and 1.11a all changed to 1.A within this time. The time and rate of this antigenic switch were characteristic for each VAT. Growth rates of the VATs were determined when they were both grown separately and grown with 1.A. It appeared that the order of growth rates was 1.7a greater than 1.A = 1.1a greater than 1.11a greater than 1.5a greater than 1.3a. We have generated theoretical curves for the replacement of one VAT by another based on differences in their growth rates and the rate at which one VAT switches to another (switch frequency). These curves closely match those derived experimentally. We postulate that the differences in growth rates between VATs and the different switch frequencies for VATs may be sufficient to generate the loosely defined sequence of VATs seen in chronic infections. PMID- 2579028 TI - Unresponsiveness to experimental allergic encephalomyelitis in Lewis rats pretreated with complete Freund's adjuvant. AB - A single injection of complete Freund's adjuvant blended with aluminum hydroxide gel (ALU-CFA) was successfully used to prevent clinical as well as histologic experimental allergic encephalomyelitis (EAE) in Lewis rats for more than 330 days. Adjuvant preparations with Mycobacterium tuberculosis were more potent than those with Mycobacterium butyricum. Neither the removal of the ALU-CFA inoculum nor a splenectomy 1 month after immunization arrested the adjuvant induced unresponsiveness. However cyclophosphamide restored responsiveness in more than half of the treated animals when applied 2 days before the encephalitogenic challenge at a dose of 20 mg/kg. Passive EAE was not prevented by the ALU-CFA pretreatment. The disease was induced by the transfer of 4 X 10(6) T lymphocytes of a cell line reactive against myelin basic protein. This indicates that the adjuvant prevents EAE at the inductive rather than at the effector phase of the autoimmune response. PMID- 2579029 TI - Mast cell heterogeneity in man. I. Histologic studies of the intestine. AB - We have studied the distribution and abundance of histochemically distinct mast cell subpopulations in the normal small and large intestine of man. One subpopulation has histochemical properties similar to the functionally distinct intestinal mucosal mast cell (MMC) of the rat and the other has properties similar to the widely distributed mast cell found in connective tissues and the peritoneal cavity of many animals. Both subpopulations are present in intestinal epithelium, lamina propria, submucosa and muscularis mucosa, and muscle. However, the subpopulation histochemically similar to the rodent MMC is significantly more abundant than the other in all sites in the large intestine and also in the lamina propria and muscle of the small intestine. It is important to determine whether these histochemically distinct mast cell subpopulations in man differ in their responses to various secretagogues and antiallergic compounds as in the rat. PMID- 2579030 TI - Characterization and partial purification of human milk fat globule membrane antigens by polyacrylamide gel electrophoresis and immunoblotting using monoclonal antibodies. AB - Polyclonal and monoclonal antibodies were used to characterize human milk fat globule (HMFG) membrane antigens, using gel filtration, ion exchange chromatography and western blotting. Although originally generated against HMFG, monoclonal antibodies also reacted with skim milk. In western blotting, several antigen molecules were seen, of which some were detected by all available antibodies, and one only with monoclonal antibody III D5, previously shown to react with mammary and ovarian carcinomas bearing estrogen receptors. This or these antigens, with a molecular weight of about 53 kd, were isolated by fractionation in SDS-PAGE. A low polypeptide content was demonstrated but the antigenic structure could be stained with periodic-acid-Schiff and biotinylated peanut agglutinin, indicating the presence of galactose or N-acetylgalactosamine residues. While this 53-kd molecule is the only determinant exclusively stained by III D 5 antibody, it is suggested that it carries epitopes related to estrogen receptor activation. PMID- 2579031 TI - Pregnancy-associated beta 1-macroglobulin: detection on the surface of ovarian cancer cell lines. AB - Pregnancy-associated beta 1-macroglobulin (beta 1-PAM) is a serum protein which can be detected at elevated levels in the blood of many ovarian cancer patients. The presence of the antigen was investigated on the surface of 4 human ovarian cancer lines and 32 other human and rodent cell types and lines by means of immunofluorescent staining and anti-beta 1-PAM-enzyme conjugate. The antigen was detected only on the ovarian lines but no secretion of beta 1-PAM into the culture supernatants was observed. The ovarian cancer cells appeared to display the beta 1-PAM constantly during culture, and enzymic treatment of the cells indicated that detection of the cell-bound antigen with antiserum could be, at least partially, eliminated with proteases but not glycosidases or neuraminidase. The results serve to confirm the association of beta 1-PAM with ovarian cancer. PMID- 2579032 TI - Modulatory effects of 5-azacytidine, phorbol ester, and retinoic acid on the malignant phenotype of human lung cancer cells. AB - Cloned human cell lines of squamous-cell lung carcinoma and small-cell lung carcinoma were treated with 5-azacytidine (5-azaC), 12-0-tetradecanoyl-phorbol-13 acetate (TPA), retinoic acid (RA), or a combination of these drugs, and the effects on cellular morphology, in vitro growth properties, antigenicity, tumorigenicity and metastatic activity in nude mice were studied. Antigenicity was measured by the expression of major histocompatibility antigens (MHC) and of lung-tumor-associated antigens. 5-AzaC treatment resulted in subclones with shorter population doubling times (from 40-50 hr down to 14-20 hr) and increased cloning efficiencies (from less than 1% to 5-50%). TPA and RA induced loss of proliferative activity in vitro and tumorigenicity in vivo of both lines. This was morphologically associated with the appearance of an abundance of large vaculated cells which by DNA-analysis were all found to be in G0-G1 phase. However, 2 of the 5-azaC-treated subclones were insensitive to both TPA and RA, whereas the remaining subclones (20) all responded like untreated lines to TPA and RA. One of the sublines insensitive to TPA and RA formed metastases in nude mice in contrast to all the other lines used. The density of lung-tumor associated antigens was significantly reduced by TPA-RA treatment, whereas the expression of MHC antigens was unaffected. In contrast, 5-azaC resulted in some cases in increased density of MHC antigens. The effects of 5-azaC on cellular phenotypes were not directly correlated to the total genomic content of 5 methylcytosine. The data suggest that this experimental system is suitable for studies of phenotypic features of malignant cells as related to cellular differentiation. PMID- 2579033 TI - Changes in fibronectin synthesis and binding distribution in SV40-transformed human keratinocytes. AB - We have studied the synthesis and distribution of fibronectin in human epidermal keratinocytes infected by SV40, a system in which the acquisition of transformed properties occurs in a sequential and progressive manner. Immunofluorescence studies showed that cultured uninfected keratinocytes do not exhibit fibronectin on the superficial cell surface, but that virus-infected cells come to display superficial fibronectin-containing cables in a density-dependent manner after a certain point in the transformation process. In contrast, organized arrays of fibronectin-containing fibrils associated with the cell-substrate attachment complex were seen in uninfected keratinocytes and in virus-infected cells at all stages of the transformation process. Studies of fibronectin synthesis using metabolic labelling of cell proteins with 35S methionine showed that viral infection caused a striking increase in overall fibronectin synthesis, although with a much higher proportion of newly synthesized fibronectin being secreted into the cell culture medium than in the case of the uninfected cells. PMID- 2579034 TI - Expression of ki-ras oncogene in tumor cell variants exhibiting different metastatic capabilities. AB - The expression of oncogenes in well-characterized B16 melanoma and UV-2237 fibrosarcoma cell variants that exhibit distinct metastatic properties was explored. The search for the expression of 11 different oncogenes revealed that the major oncogene in those two tumor systems is the Kirsten-ras (ki-ras). The results indicate that the amounts of specific ki-ras mRNA and the p21 protein are similar in both low- and high-metastatic counterparts. These results suggest that in these systems there is no apparent direct correlation between the amount and expression of the major cellular oncogene so far identified and the metastatic potential of these tumor cells. PMID- 2579035 TI - The plasmin system in human colonic tumors: an immunofluorescence study. AB - We studied the plasmin system with specific antisera to plasminogen, its 2 activators (urokinase-type and tissue-type) and the 2 plasmin inhibitors, alpha 2 anti-plasmin and alpha 2 macroglobulin on sections of 34 human colonic tumors by immunofluorescence. Anti-plasminogen serum showed a clear-cut reactivity at the surface of tumor cells, as it stained the contour of tumor glandular structures, foci, and isolated tumor cells. Intratumoral deposits and necrotic areas were stained as well, often strongly. Localization of plasminogen was quite different from that of fibrinogen, which was found only in peritumoral stroma, and never on tumor cells. Traces of both types of plasminogen activator were found, mainly on invasive tumor cells for urokinase type and on large tumor foci for tissue type. Images were weak and inconstant. Large amounts of both plasmin inhibitors were characterized in tumor stroma. Alpha-2 anti-plasmin was also found in intratumoral deposits and necrotic areas. It seems likely that plasminogen exudes from blood capillaries (since anti-plasminogen serum often stained the whole capillary wall), diffuses in the stroma and binds to tumor cells. Once formed, plasmin is likely to play a role in the invasion of surrounding tissues by tumor cells, in the dissociation of tumor cells from tumor glands and in the production of necrosis inside tumor areas. PMID- 2579036 TI - Biosynthesis of alpha fetoprotein by MCF-7 human breast cancer cells. AB - Direct evidence was obtained for de novo synthesis of AFP by MCF-7 human breast cancer cells per se. Synthesis was demonstrated by L-14C-leucine and L-35S methionine incorporation into immunochemically isolated AFP, and confirmed by radioimmunodiffusion and radioimmunoelectrophoresis. This information indicates that AFP synthesis is associated with normal and neoplastic cells of several different histotypes, and suggests that AFP detected and measured previously in primary human breast cancer tissue cytosol (Sarcione et al., 1983) also resulted from in situ biosynthesis by breast cancer cells per se rather than uptake of exogenous AFP originating from extracellular sources. Evidence that AFP obtained after treatment of 14C-leucine radiolabelled MCF-7 breast cancer cell protein with 0.4 M KCl contained 2.6 times more radioactivity than did AFP obtained before such salt treatment is interpreted as indicating that two different molecular species of de novo synthesized AFP existed in breast cancer cells: (1) larger amount of non-immunoreactive AFP which became immunoreactive and measurable after KCl treatment, and (2) smaller amounts of free immunoreactive AFP. 14C-radiolabelled AFP obtained before and after treatment of cell protein with 0.4 M KCl codiffused, comigrated with alpha 1 electrophoretic mobility and gave an identical radioimmunologic reaction both with each other and with added carrier human cord serum AFP. Furthermore, preliminary studies indicated that radiolabelled non-immunoreactive AFP could be separated from lower-molecular weight free AFP by chromatography on Sephadex G-200. Taken together, these findings suggest that synthesized free AFP was bound as a non-immunoreactive high molecular-weight macromolecular complex rather than being covalently linked. Our current working hypothesis is that most of the de novo synthesized endogenous AFP in MCF-7 human breast cancer cells was rapidly and reversibly bound by hydrophobic bonding to a specific cytoplasmic AFP-receptor. PMID- 2579037 TI - Generation of Epstein-Barr virus antigen-specific suppressor T cells in vitro. AB - Immunosuppression is a commonly observed phenomenon in Epstein-Barr virus (EBV) associated disorders and malignancies. The purpose of this study was to determine whether EBV antigens could generate suppressor cell activity in vitro. Peripheral blood lymphocytes (PBL) were first treated with various concentrations of EBV antigens or culture medium for 5 days and then with mitomycin C. The cells were then washed and tested for their ability to abrogate the blastogenic response of fresh, autologous PBL to previously determined optimal concentrations of EBV antigens. It was found that excess of both EBV antigens tested (soluble antigen and virus particles) induced suppressor cells, while optimal antigen concentrations failed to do so. In addition, PBL incubated with excess of EBV antigens for 10 days, without mitomycin treatment, inhibited the response of fresh autologous lymphocytes to EBV antigens. The generated suppressor cells were found to be antigen-specific since they inhibited the response of sensitized lymphocytes to the inducing antigen only. Moreover, experiments performed using purified lymphocyte subpopulations indicated that the suppressor activity was associated with T-cell populations. Using T-cells specific monoclonal antibodies, we further determined that the inhibitory activity was due to suppressor (OKT 8+) T-lymphocytes; treatment of T-lymphocyte populations (exhibiting suppressor activity) with OKT 8 antibody and complement abrogated the inhibitory effect of these populations on the response of sensitized lymphocytes to EBV antigens. Taken together, these observations suggest that similar suppressor cells may be at least partly responsible for the immunosuppression observed in patients with an antigenic overload, particularly during persistently active virus infection or malignancy. PMID- 2579038 TI - Isolation of simian retroviruses closely related to human T-cell leukemia virus by establishment of lymphoid cell lines from various non-human primates. AB - Simian retroviruses closely related to human T-cell leukemia virus (HTLV) were isolated by establishing virus-producing lymphoid cell lines from 7 species of non-human primates. By co-cultivation with human umbilical cord-blood cells and/or in the presence of interleukin-2, lymphoid cell lines were successfully established from the chimpanzee. African green monkey, pig-tailed macaque, red faced macaque, Formosan monkey, Japanese monkey and bonnet monkey that had antibodies against HTLV antigens. These cell lines reacted with human sera of ATL patients and monoclonal antibodies against p19 and p24 of HTLV antigens. Cellular DNAs contained the provirus sequences homologous to HTLV-I by Southern blot hybridization. Moreover, they produced extracellular type-C virus particles and RNA-dependent DNA polymerase. All of these lymphoid line cells had Tac antigen, interleukin-2 receptor, and those of chimpanzee and red-faced macaque had helper/induced T-cell markers, while those derived from African green monkey had suppressor/cytotoxic T-cell markers. Furthermore, simian HTLV-related viruses of pig-tailed macaque, red-faced macaque and Japanese monkey were transmitted to human lymphocytes on co-cultivation. PMID- 2579039 TI - Malignant melanoma: cross-reacting (common) tumor rejection antigens. AB - The expression of tumor-associated transplantation antigens (TATA) by 3 different murine melanomas was examined. A comparison was made between different modes of inducing tumor-rejection activity, including immunization with irradiated cells from tissue culture lines, with irradiated cells from solid tumor lines, and with viable cells growing in footpads (followed by amputation). Melanoma cell lines examined included the spontaneous B16 melanoma, the ultraviolet-light-induced K1735 melanoma, and the dimethylbenzanthracene-induced JB/RH melanoma. The data presented demonstrate that not only do all 3 melanoma lines studied express cell surface antigens sufficient to elicit immune response which result in tumor rejection activity, but that these antigens show crossreactivity among the 3 melanoma lines studied. The specificity of the TATA appear to be restricted to the melanomas, since crossreactivity was not observed with 2 different fibrosarcoma cell lines, or with 2 sarcoma cell lines. In addition, it was found that both the JB/RH and K1735 melanoma cells release (or shed) cell surface antigens which can elicit tumor rejection activity, and that these antigens can be extracted with aqueous butanol, as has been demonstrated with B16 melanoma. PMID- 2579040 TI - Lysis of herpes simplex virus (HSV) infected targets. III. Effect of HSV on natural killer activity. AB - Freshly isolated peripheral blood lymphocytes from patients (PBL-P) with recurrent herpetic corneal and skin lesions, and controls (PBL-C) with no recollection of herpetic disease, effectively lysed herpes simplex virus type 1 (HSV-1) infected but not uninfected allogeneic fibroblasts. However, after 48 hr of stimulation with HSV-1, the lytic activity of PBL-C declined, while that of PBL-P increased. PBL-P and PBL-C produced similar amounts of interferon when stimulated with HSV-1. Thus, the decline in lytic activity by HSV-1 stimulated PBL-C was not due to a lack of interferon production. Interestingly, the lytic activity of HSV-1 stimulated PBL appeared to be directed against a component commonly expressed on both uninfected and HSV-1 infected fibroblasts. This was indicated by the fact that after incubation with HSV-1, PBL-P lysed the uninfected fibroblasts as effectively as the HSV-1 infected fibroblasts. The augmented lysis of uninfected fibroblasts was not due to infection of the "uninfected fibroblasts" by HSV-1 carried over or produced by the HSV-1 stimulated PBL. Furthermore, the capacity of HSV-1 to augment lytic activity was not diminished markedly by ultraviolet irradiation, suggesting that augmentation is due to the stimulatory capacity rather than the infectivity of the virus. Our data show that interaction of PBL-P with HSV-1 results in enhancement of nonspecific lytic activity and loss of the capacity to discriminate HSV-1 infected from uninfected allogenic fibroblasts. PMID- 2579041 TI - Molecular basis of an inherited retinal defect in Drosophila. AB - Fruitflies carrying the autosomal recessive mutation transient receptor potential (trp) are blind in bright light because the receptor potential of such a mutant decays almost completely during an intense stimulus. The trp gene has been localized and a set of partially overlapping genomic clones that include the trp gene has been isolated. The stretch of DNA represented by these genomic clones is found to contain genes that encode for four RNA species. Two of these RNA species are missing in the mutant. This observation is consistent with the notion that the mutation alters the DNA sequence in a region containing signals necessary for the expression of the gene. Accordingly, the molecular basis of the mutant phenotype may be due to the lack of a protein(s) that is/are important for normal visual transduction. PMID- 2579042 TI - Density profile of blue-sensitive cones along the horizontal meridian of macaque retina. AB - Intravitreal injection of some fluorescent and nonfluorescent tissue-reactive dyes results in selective intracellular staining of a specific population of cones of macaque retina that have been identified tentatively as blue-sensitive cones. This paper describes quantitative density profiles of these cones as a function of retinal eccentricity. These profiles were measured from 0 deg to about 60 deg eccentricity along the nasal and temporal segments of the horizontal meridian of macaque retina. Stained cones were found to be absent from the very center of the fovea. These cones reach peak densities at 0.75-1.50 deg eccentricity, and decrease with greater eccentricity, more rapidly on the temporal than on the nasal segment of the horizontal meridian. Peak densities were found to be slightly closer to the foveal center of the retinas of adult male than of adult female macaques. Packing patterns of stained and unstained cones are discussed as is the mathematic expression of stained cone distribution. The spatial properties of the retinal distribution of stained cones agree very closely with those obtained in psychophysical human studies and other anatomic simian studies of blue-sensitive cones. PMID- 2579044 TI - Digital subtraction angiography. Comparison of meglumine-Na diatrizoate with iohexol. AB - A slight improvement in image quality occurred with the use of iohexol when compared with meglumine-Na diatrizoate. There is less swallowing with iohexol, which gives better image registration when looking at the extracranial carotid arteries. A single significant tachycardia occurred with the ionic medium, but not with iohexol. Overall discomfort and minor adverse reactions were less with iohexol than with diatrizoate. PMID- 2579043 TI - Development of nonionic contrast media. AB - In this brief history, the author reviews the observations that led to his developing a nonionic contrast medium. Current knowledge suggested that if a water-soluble medium could be made isotonic to human plasma, it would cause less pain and toxicity than the ionic media then in use. The principles and design of such a medium are discussed, as well as the subsequent chemical development and testing in animal models of first generation (metrizamide) and second generation (iohexol) nonionic media. Iohexol, which is described as a nonionic, monomeric ratio 3 contrast medium, was selected for clinical testing from among competing substances due to its low toxicity in a number of animal models. The results from these experimental models predicted that iohexol would cause fewer and less severe adverse reactions in clinical use than ionic ratio 1.5 media. PMID- 2579045 TI - Etiology of anaphylactoid responses. The promise of nonionics. AB - Though the precise etiology of anaphylactoid contrast media reactions is unknown, recent investigations have contributed important insight into their pathogenesis. Explorations of the complement and coagulation systems, the basophil histamine release system, and antigen-IgE interactions are summarized. Current investigations focusing on the contact system are discussed. Patients with asthma and patients who are contrast material reactors show increased prekallikrein transformation rates indicating increased contact system activity. Increased endogenous heparin-like material was found in asthmatic patients and in 50% of prechallenge citrated plasmas of patients who later developed contrast reactions, suggesting partial explanation of increased incidence of reactions in asthmatics. Elevated heparin-like material may have pathogenic significance; it may potentiate prekallikrein transformation and inhibit adenylate cyclase to induce release of inflammatory mediators and produce bronchospasm. When appropriately administered, glucocorticoids appear to protect against contrast reactions. Incidence of systemic anaphylaxis with nonionic contrast media is unknown but is expected to be less than that with ionic media. Additional experience is needed to assess this potential benefit of nonionics. PMID- 2579046 TI - Chemotoxicity of contrast media and clinical adverse effects: a review. AB - The clinical effects of contrast agents not only result from high osmolality, but also from their own specific pharmacology, which mediates chemotoxic effects. In this review, the chemotoxic effects of the new nonionic agent, iohexol, are compared with those of standard ionic and other low osmolality contrast agents, ionic and nonionic. Iohexol has the lowest chemotoxicity of any agent yet synthesized. Its low systemic toxicity is the combined result of low chemotoxicity and low osmolality. Mechanisms of severe adverse reactions are reviewed, including the views of Lasser and Lalli, and the view that emphasizes the importance of cardiotoxic and hemodynamic effects. It is concluded that whichever view is taken of the mechanisms of severe adverse reactions, the new nonionic agents are likely to be safer than the ionic agents now in use. PMID- 2579047 TI - Hepatocellular carcinoma in Israel: relationship to hepatitis B virus infection. AB - The possible relationship between hepatocellular carcinoma (HCC) and hepatitis B virus infection in Israel was evaluated. A retrospective study of 40 cases with HCC in Israel revealed irregular (macronodular) cirrhosis in 37 of 40 cases (92.5%). Hepatitis B surface antigen (HBsAg), demonstrated by the immunoperoxidase technique, was found in the nontumorous liver tissue of 20 of 40 (62.5%) of the patients. alpha-Fetoprotein was positive in the tumor cells by the immunoperoxidase method in 22 of 40 (55%) of cases. Population subgroups with relatively high HBsAg carrier rates did not show a higher incidence of HCC. However, an inexplicably high rate of HCC was found in patients of Rumanian origin, regardless of HBsAg expression. The present study indicates that in Israeli patients with HCC, there is a relatively higher incidence of HBsAg in the liver tissue than in patients in other countries with a similarly low incidence of HCC. PMID- 2579048 TI - Concealed atrioventricular conduction. PMID- 2579049 TI - [Evaluation of cobalt 57-labeled bleomycin scintigraphy in the preoperative diagnosis of a pulmonary radiological image]. PMID- 2579051 TI - Management of malignant airway obstruction: clinical and dosimetric considerations using an iridium-192 afterloading technique in conjunction with the neodymium-YAG laser. AB - Fourteen patients with malignant airway obstruction have had 21 placements of a flexible nylon catheter for afterloading Iridium-192 using the flexible fiberoptic bronchoscope. Prescribed therapy was completed in 13 patients (18 courses). All patients had prior full-dose external irradiation, and no effective surgical or chemotherapeutic options remained. While many have had a trial of neodymium-YAG (yttrium-aluminum-garnet) laser therapy alone, eight patients received laser treatment one to three weeks prior to planned brachytherapy to provide immediate relief of symptoms and/or facilitate access and safe catheter placement. Most patients (64%) had recurrent squamous cell lung cancer. A dose of 3000 cGy is currently specified to 5 mm and 10 mm in the bronchus and trachea, respectively. Nine of the 13 treated patients have had follow-up bronchoscopy at approximately three months post-treatment with improvement documented in seven and progression in two patients. One patient was clinically improved without follow-up bronchoscopy, and three patients have had insufficient follow-up. A single patient treated with laser and 6000 rad at 5 mm developed a bronchoesophageal fistula. No other complication has been observed. The technique is simple and safe with the use of laser therapy when needed and appears to offer effective palliation in most patients even when standard therapy is exhausted. PMID- 2579052 TI - Malignant obstructive jaundice: treatment with external-beam and intracavitary radiotherapy. AB - Eleven patients with obstructive jaundice from unresectable cholangiocarcinoma, metastatic porta hepatis adenopathy, or direct compression from a pancreatic malignancy were treated at the Stanford University Medical Center from 1978-1983 with an external drainage procedure followed by high-dose external-beam radiotherapy and by an intracavitary boost to the site of obstruction with Iridium192 (Ir192). A median dose of 5000 cGy was delivered with 4-6 Mv photons to the tumor bed and regional lymphatics in 9 patients, 1 patient received 2100 cGy to the liver in accelerated fractions because of extensive intrahepatic disease, and 1 patient received 7000 "equivalent" cGy to his pancreatic tumor bed and regional lymphatics with neon heavy particles. An Ir192 wire source later delivered a 3100-10,647 cGy boost to the site of biliary obstruction in each patient, for a mean combined dose of 10,202 cGy to a point 5 mm from the line source. Few acute complications were noted, but 3/11 patients (27%) subsequently developed upper gastrointestinal bleeding from duodenitis or frank duodenal ulceration 4 weeks, 4 months, and 7.5 months following treatment. Eight patients died--5 with local recurrence +/- distant metastasis, 2 with sepsis, and 1 with widespread systemic metastasis. Autopsies revealed no evidence of biliary tree obstruction in 3/3 patients. Mean survival time from initial laparotomy and bypass was 16.1 months, and from radiotherapy completion was 8.3 months. Evolution of radiation treatment techniques for biliary obstruction in the literature is reviewed. High-dose external-beam therapy followed by high-dose Ir192 intracavitary boost is well tolerated and provides significant palliation. Survival of these aggressively managed patients approaches that of patients with primarily resectable tumors. PMID- 2579050 TI - Precision, high dose radiotherapy: helium ion treatment of uveal melanoma. AB - We report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) we have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons. PMID- 2579053 TI - Molecular structure of heliomycin, an inhibitor of RNA synthesis. PMID- 2579055 TI - Amplification of the antibiotic effects of the bleomycins, phleomycins and tallysomycins: its dependence on the nature of the variable basic groups. AB - The bleomycins, phleomycins and tallysomycins are structurally similar glycopeptide antibiotics. Within each class, individual members differ only in the structure of a basic group. The antibiotic effect of phleomycin (Bristol batch A9331-648) against Escherichia coli is amplified substantially by a number of simple heterocyclic and aromatic compounds. In this paper a sample of 26 such compounds were tested for this property with 25 different phleomycins, bleomycins and tallysomycins. The nature of the variable basic group of the phleomycins, bleomycins and tallysomycins determined the response obtained with all amplifiers, although variation of response was much less marked with caffeine which potentiated the cytotoxic effects of all the phleomycins, bleomycins and tallysomycins tested. Phleomycins and bleomycins having two or three guanidino groups in the variable basic group, or phleomycins having a secondary amino group within a methylene chain and a terminal 2-phenylethyl substituent, were amplified by most compounds, whereas the cytotoxicity of others was enhanced little or not at all. Similar phleomycins, having a secondary amino and a terminal guanidino group and no 2-phenylethyl substituent showed little enhancement, and in these cases the inclusion of a 2-phenylethyl substituent had a major influence in determining amplifiability. Bleomycins and phleomycins having identical basic groups were amplified to similar extents by the sample of 26 amplifying agents used. PMID- 2579054 TI - Immunological involvement in pulmonary fibrosis induced by peplomycin. AB - Pulmonary fibrosis in mice induced by peplomycin (PEP) was suppressed by administration of anti-inflammatory agents such as prednisolone and D penicillamine during or after the administration of PEP. Pulmonary fibrosis was also suppressed by administration of cyclophosphamide, an immunosuppressive antitumor agent before, during or after the administration of PEP. The pulmonary fibrosis in athymic nude mice induced by PEP was less than that in normal mice. The low response in the nude mice was enhanced by transfer of thymocytes to the same level as that in the normal mice. This suggests that the immune system, especially thymus-dependent immunity, is involved in the pulmonary fibrosis induced by PEP. PMID- 2579056 TI - Poster session displays. PMID- 2579057 TI - Poster session presentations--their impact on biophotography and the process of preparation. PMID- 2579058 TI - Cell-bound and secreted proteases of Serratia marcescens. AB - Exoprotease of Serratia marcescens ATCC 25419 is exceptional among members of the family Enterobacteriaceae in that it is secreted in large amounts by viable cells into the culture medium. Labeling of cells with radioactive amino acids revealed no intracellular protein that could be precipitated with antibodies raised against purified exoproteases. With substances known to interfere with the excretion of some proteins--tosyl-L-lysine chloromethyl ketone, phenethyl alcohol, procaine, and sodium azide--and with rifampin, an intracellular form (apparent molecular weight, 52,000) larger than the major exoform (molecular weight, 51,000) was identified. Moreover, the 52,000-molecular-weight form was the main protein in immunoprecipitates of a cysteine-auxotrophic mutant starved for cysteine. Beside the major exoform, protease I, two additional exoproteases, termed II and III, appeared in the medium of stationary cultures. They were precipitated by antibodies against protease I, were identical in the Ouchterlony double-diffusion assay, and exhibited only a small difference, if any at all, in the peptide pattern after partial hydrolysis with protease V8 of Staphylococcus aureus. The amino- and carboxy-terminal amino acid sequences of protease I and II were determined and found to be identical, NH2-Ala-Ala-Thr-Gly-Gly-Tyr-Asp-Ala Val-Asp and Phe-Ile-Val-COOH, respectively. The microheterogeneity of the isolated exoforms revealed by anion-exchange chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis was also observed in samples pulse labeled with radioactive amino acids. It remains to be determined whether the different protease forms are the result of processing (modification) reactions or whether they constitute isoenzymes encoded by very similar genes. PMID- 2579059 TI - Escherichia coli 6S RNA is not essential for growth or protein secretion. AB - The function of the stable 6S RNA of Escherichia coli is not known. Recently, it was proposed that the 6S RNA is a component of a bacterial signal recognition particle required for protein secretion. To test this proposal, we isolated a mutant that lacks the 6S RNA. Studies of the mutant show that the 6S RNA is not essential for growth or for protein secretion. The gene for the 6S RNA (ssr) maps near serA at 63 min on the E. coli genetic map. PMID- 2579060 TI - Escherichia coli 6S RNA gene is part of a dual-function transcription unit. AB - The gene coding for the metabolically stable 6S RNA of Escherichia coli has been cloned, sequenced, and partially characterized in expression analyses. The DNA sequence results confirm the accuracy of the previously established RNA sequence and, with genomic hybridization data, reveal that there is only one copy of the 6S DNA in the chromosome. Consistent with its relaxed mode of expression, the promoter region of the 6S RNA gene was found to lack the hypothetical GC-rich discriminator domain common to other stable RNA genes under stringent control. The sequence results also revealed the occurrence of a 540-base-pair open reading frame immediately downstream from the 6S RNA coding region. Results from the expression analyses show that the protein and RNA coding regions are cotranscribed in vitro and that the open reading frame is translated in vivo. PMID- 2579062 TI - Polycistronic mRNAs code for polypeptides of the Vibrio harveyi luminescence system. AB - DNA coding for the alpha and beta subunits of Vibrio harveyi luciferase, the luxA and luxB genes, and the adjoining chromosomal regions on both sides of these genes (total of 18 kilobase pairs) was cloned into Escherichia coli. Using labeled DNA coding for the alpha subunit as a hybridization probe, we identified a set of polycistronic mRNAs (2.6, 4, 7, and 8 kilobases) by Northern blotting; the most prominent of these was the one 4 kilobases long. This set of mRNAs was induced during the development of bioluminescence in V. harveyi. Furthermore, the same set of mRNAs was synthesized in E. coli by a recombinant plasmid that contained a 12-kilobase pair length of V. harveyi DNA and expressed the genes for the luciferase subunits. A cloned DNA segment corresponding to the major 4 kilobase mRNA coded for the alpha and beta subunits of luciferase, as well as a 32,000-dalton protein upstream from these genes that could be specifically modified by acyl-coenzyme A and is a component of the bioluminescence system. V. harveyi mRNA that was hybridized to and released from cloned DNA encompassing the luxA and luxB genes was translated in vitro. Luciferase alpha and beta subunits and the 32,000-dalton polypeptide were detected among the products, along with 42,000- and 55,000-dalton polypeptides, which are encoded downstream from the lux genes and are thought to be involved in luminescence. PMID- 2579063 TI - A case of mania secondary to propafenone. AB - A case of mania secondary to the administration of a new antiarrhythmic, propafenone, is described. This is a previously unrecognized potential complication in the use of this agent. Since propafenone is chemically related to a new antidepressant, bupropion, it may possess some antidepressant activity and thus have the potential to produce affective psychiatric side effects. PMID- 2579061 TI - Genetic study of the functional organization of the colicin E1 molecule. AB - Colicin E1 fragments obtained by genetic manipulations of the ColE1 plasmid were tested for bactericidal activity, binding to bacterial cells, and reactions with a series of anticolicin monoclonal antibodies. Two of the fragments were also tested for ability to form channels in liposomal vesicles. The results are in agreement with studies from chemically and enzymatically derived colicin fragments, assigning the receptor binding activity to the central part of the molecule and the killing activity to a region near the carboxyl terminus. PMID- 2579064 TI - Photoaffinity labeling of the D2-dopamine receptor using a novel high affinity radioiodinated probe. AB - The ligand binding subunit of the D2 subtype of the dopamine receptor has been identified by photoaffinity labeling. In order to develop a specific covalent receptor probe, an analogue of the potent D2 selective antagonist spiperone, N-(p aminophenethyl)spiperone (NAPS) has been synthesized. The aminophenethyl substituent of NAPS can be radioiodinated to theoretical specific radioactivity (2,175 Ci/mmol) and then the arylamine group converted to an arylazide to yield a photosensitive probe [( 125I]N3-NAPS). In rat striatal membranes, the nonradiolabeled azide probe (N3-NAPS) binds to the receptor with high affinity (KD congruent to 1.6 +/- 0.05 nM) and upon photoactivation irreversibly decreases the number of available receptors in these membranes as measured by [3H]spiperone binding. More importantly, however, incubation of rat striatal membranes with [125I]N3-NAPS leads to the photodependent covalent incorporation of the probe into a peptide of Mr = 94,000 as assessed by autoradiography of gels after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Labeling of this Mr = 94,000 peptide can be blocked specifically and stereoselectively by dopaminergic antagonists such as (+)- and (-)-butaclamol but not by non-dopaminergic antagonists. Moreover, dopaminergic agonists also attenuate the covalent labeling of this peptide with an order of potency which is typically D2-dopaminergic. Therefore, the specificity of [125I]N3-NAPS labeling of the Mr = 94,000 peptide suggests that this peptide represents the ligand binding subunit of the D2 dopamine receptor. PMID- 2579065 TI - Tissue specific expression and developmental regulation of two genes coding for rat fatty acid binding proteins. AB - We have examined the tissue distribution and developmental regulation of two low molecular weight cytosolic fatty acid binding proteins. Based on their initial site of isolation, they have been referred to as liver and intestinal fatty acid binding proteins (FABP). Cloned cDNAs were used to probe blots of RNAs extracted from a wide variety of adult rat tissues as well as small intestine and liver RNA obtained from fetal, suckling, and weaning animals. The highest concentrations of "liver" FABP mRNA were found in small intestine and liver. "Intestinal" FABP mRNA is most abundant in small bowel RNA while only trace amounts were encountered in liver. Both mRNAs were detectable in stomach, colon, pancreas, spleen, lung, heart, testes, adrenal, and brain RNA at 1-8% the concentrations observed in small intestine. Accumulation of both mRNAs in the small intestinal epithelium increases during development. The mRNAs are first detectable between the 19th and 21st day of gestation. They undergo a coordinated 3-4-fold increase in concentration within the first 24 h after birth. Thereafter, gut levels of intestinal FABP mRNA remain constant during the suckling period while liver FABP mRNA increases an additional 2-fold. Liver FABP mRNA levels are also induced in hepatocytes during the first postnatal day but subsequently do not change during the suckling and weaning phase, despite marked alterations in hepatic fatty acid metabolism. These observations support the concept that the major role of these proteins is to facilitate the entry of lipids into cells and/or their subsequent intracellular transport and compartmentalization. The data also raise questions about the identity of extragastrointestinal FABPs. PMID- 2579067 TI - The human placenta contains two distinct binding and immunoreactive species of insulin-like growth factor-I receptors. AB - Two species of insulin-like growth factor-I (IGF-I) receptors in human placenta have been delineated on the basis of their immunoreactivity with an autoantiserum (B-2) to the insulin receptor. When all the IGF-I binding sites in solubilized human placenta were assayed by polyethylene glycol precipitation, a curvilinear Scatchard plot was obtained which could be resolved into two single classes of binding sites: one immunoprecipitable by B-2 IgG and the other, nonimmunoprecipitable. The B-2 reactive sites bound IGF-I with lower affinity (Kd = 7.1 X 10(-10) M) than the B-2 nonreactive sites (Kd = 2.1 X 10(-10) M) and cross-reacted more readily with insulin, the IGF-I/insulin-binding potencies being congruent to 120 and congruent to 1100, respectively. Both receptor subtypes bound IGF-I with congruent to 30-fold higher affinity than multiplication-stimulating activity, and, after affinity cross-linking with 125I IGF-I, migrated as specific reduced bands of Mr = 138,000 during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The subunit sizes of the B-2 reactive IGF-I receptor were similar to those of the insulin receptor. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 125I-labeled receptors immunoprecipitated by autoantiserum B-2 or autoantiserum B-10 (which recognizes only insulin receptors) revealed, in both cases, specific reduced bands of Mr = 130,000 and 90,000; the same bands were also seen after sequential precipitation with B-10 and B-2 antisera to enrich the proportion of IGF-I receptors recovered. The presence of two distinct binding and immunoreactive species of IGF-I receptors in human placenta raises the possibility that cell- or tissue-specific isotypes of the IGF-I receptor could mediate the different biological actions of IGF-I. PMID- 2579066 TI - Isolation and sequence analysis of a cDNA clone encoding the fifth complement component. AB - We have used available protein sequence data for the anaphylatoxin (C5a) portion of the fifth component of human complement (residues 19-25) to synthesize a mixed sequence oligonucleotide probe. The labeled oligonucleotide was then used to screen a human liver cDNA library, and a single candidate cDNA clone of 1.85 kilobase pairs was isolated. Hybridization of the mixed-sequence probe to the complementary strand of the plasmid insert and sequence analysis by the dideoxy method predicted the expected protein sequence of C5a (positions 1-12), amino terminal to the anticipated priming site. The sequence obtained further predicted an arginine-rich sequence (RPRR) immediately upstream of the N-terminal threonine of C5a, indicating that the promolecule form of C5 is synthesized with a beta alpha-chain orientation as previously shown for pro-C3 and pro-C4. The C5 cDNA clone was sheared randomly by sonication, subcloned into M13 mp8, and sequenced at random by the dideoxy technique, thereby generating a contiguous sequence of 1703 base pairs. This clone contained coding sequence for the C-terminal 262 amino acid residues of the beta-chain, the entire C5a fragment, and the N terminal 98 residues of the alpha'-chain. The 3' end of the clone had a polyadenylated tail preceded by a polyadenylation recognition site, a 3' untranslated region, and base pairs homologous to the human Alu concensus sequence. Comparison of the derived partial human C5 protein sequence with that previously determined for murine C3 and human alpha 2-macroglobulin has indicated regions of pronounced sequence similarity. Examination of cytoplasmic RNA prepared from human liver and the human hepatoma cell line Hep G2 by Northern transfer has indicated a C5 mRNA species of about 5.2 kilobase pairs. PMID- 2579068 TI - Methylation of type II and type I collagen genes in differentiated and dedifferentiated chondrocytes. AB - The methyl-sensitive restriction endonucleases HpaII and HhaI as well as the methyl-insensitive enzyme MspI were used to examine the methylation status of the pro-alpha 1(II) collagen gene of cartilage. Five different cell types with varying abilities to express type II collagen were studied. Chick embryo chondrocytes express type II collagen, while 5-bromodeoxyuridine-treated chondrocytes, retinoic acid-treated chondrocytes, chick embryo fibroblasts, and erythrocytes do not synthesize type II collagen. Both cDNA and genomic probes for the pro-alpha 1(II) collagen gene were used, covering the complete 3' end of the gene and its flanking sequences. The pro-alpha 1(II) collagen DNA was undermethylated in chondrocytes, compared to either fibroblasts or erythrocytes. However, the methylation of the 5-bromodeoxyuridine-treated and retinoic acid treated chondrocytes was identical to that of control chondrocytes. The methylation pattern of two regions of the gene of the pro-alpha 2(I) collagen chain was identical in all cell types tested, whether or not the gene was expressed. Our results indicate that genes for these collagen chains differ in their methylation pattern. The type II collagen gene shows reduced methylation in expressing cartilage, but does not acquire an increase in methylation in "dedifferentiated" chondrocytes. The changes in DNA methylation that occur during cell differentiation do not appear to be sufficient to explain gene activation and deactivation. PMID- 2579069 TI - Swainsonine treatment accelerates intracellular transport and secretion of glycoproteins in human hepatoma cells. AB - We are interested in determining whether carbohydrates are important regulatory determinants in the intracellular transport and secretion of glycoproteins. In the present study, we have used swainsonine, an indolizidine alkaloid, to modify the structure of N-glycosidically linked complex oligosaccharides. By inhibiting Golgi mannosidase II, swainsonine prevents the trimming of GlcNAc(Man)5(GlcNAc)2 to GlcNAc-(Man)3(GlcNAc)2, resulting in the formation of hybrid-type oligosaccharides. We find, from pulse-chase experiments using [35S]methionine and immunoprecipitation of individual proteins from culture media, that swainsonine treatment (1 microgram/ml) accelerated the secretion of glycoproteins (transferrin, ceruloplasmin, alpha 2-macroglobulin, and alpha 1-antitrypsin) by decreasing the lag period by 10-15 min relative to untreated cultures. The enhanced secretion was specific for glycoproteins since the secretion of albumin, a nonglycoprotein, was unaffected. When alpha 1-antitrypsin was immunoprecipitated from the cell lysates, sodium dodecyl sulfate-polyacrylamide gel electrophoresis fluorographic analysis demonstrated that the conversion of the high-mannose precursor to the hybrid form in swainsonine-treated cells occurred more rapidly (by about 10 min) than the conversion to the complex form in control cells. Since both the hybrid and complex forms of alpha 1-antitrypsin are terminally sialylated by sialyltransferase in the trans-Golgi, these results suggest that swainsonine-modified glycoproteins traverse the Golgi more rapidly than their normal counterparts. Therefore, accelerated transport within this organelle may account for the decreased lag period of glycoprotein secretion in the swainsonine-treated cultures. PMID- 2579070 TI - Inhibition of phosphatidylinositol synthase and other membrane-associated enzymes by stereoisomers of hexachlorocyclohexane. AB - Hexachlorocyclohexanes (HCCH) are chlorinated analogs of inositol; the alpha, beta, gamma, and delta isomers of HCCH have the stereochemical configurations of (+/-)-, scyllo-, muco-, and myo-inositol, respectively. To assess their potential as specific tools for the study of agonist-stimulated phosphoinositide metabolism, we examined the effects of these four HCCH isomers on phosphatidylinositol (PI) synthase (CDP-1,2-diacyl-sn-glycerol:myo-inositol 3 phosphatidyltransferase), PI:inositol exchange enzyme, and several membrane associated enzymes unrelated to inositol metabolism. In pancreas microsomes, in the presence of saturating myo-inositol, the alpha, beta, gamma, and delta isomers (4 mM) inhibited PI synthase activity by 9, 4, 22, and 69%, respectively. Half-maximal inhibition by delta-HCCH occurred at 0.25 mM. A similar pattern of HCCH inhibition was obtained using n-octylglucopyranoside-solubilized and partially purified PI synthase preparations. The inhibition by delta-HCCH was noncompetitive versus myo-inositol. The PI:inositol exchange enzyme in mouse pancreas microsomes was inhibited 90% by 1 mM delta-HCCH in the presence of 0.25% Triton X-100, but not in its absence; half-maximal inhibition occurred with 0.5 mM delta-HCCH. delta-HCCH (4 mM) also inhibited to varying extents the following enzymes: pancreas CDP-choline:1,2-diacyl-sn-glycerol cholinephosphotransferase (75%), brain and erythrocyte (Na+,K+)-ATPase (87 and 70%), brain and erythrocyte Mg2+-ATPase (38 and -5%), brain 1,2-diacyl-sn-glycerol kinase (22%), and liver glucose 6-phosphatase (16%). gamma-HCCH (4 mM) inhibited these enzymes to a lesser extent, or not at all. The order of inhibition by HCCH stereoisomers was the same as the order of their saturation level in phospholipid vesicles (delta greater than gamma greater than alpha greater than beta). This suggests that the inhibitory action is due to insertion of the compounds either into hydrophobic domains of the enzymes or into annular lipid. The results indicate that the HCCHs are not selective inhibitors of inositol metabolism. PMID- 2579071 TI - The effect of a water-soluble tris-galactoside-terminated cholesterol derivative on the fate of low density lipoproteins and liposomes. AB - A triantennary galactose-terminated cholesterol derivative, N-(tris(beta-D galactopyranosyloxymethyl) methyl)-N alpha-(4-(5-cholesten-3 beta yloxy)succinyl)glycinamide (Tris-Gal-Chol), which dissolves easily in water, was added to human low density lipoproteins (LDL) in varying quantities. Upon addition to LDL, Tris-Gal-Chol was immediately incorporated, and after intravenous injection into rats, the iodine-labeled apolipoprotein B radioactivity was readily associated with the liver. The incorporation of 5 or 13 micrograms of Tris-Gal-Chol into LDL (20 micrograms of protein) stimulates the parenchymal cell association of LDL 6- and 10-fold, respectively, at 10 min after injection. For non-parenchymal cells, the cell association is 60- and 70-fold stimulated, respectively. It can be calculated that non-parenchymal cells (mainly Kupffer cells) are for 80-90% responsible for the increased, galactose-mediated, interaction of Tris-Gal-Chol LDL with the liver. The increased interaction of LDL with the cells upon Tris-Gal-Chol incorporation is followed by degradation of the apolipoprotein B in the lysosomes. Incorporation of Tris-Gal-Chol into unilamellar liposomes (10 mol %) leads to an increased cell association of the enclosed [3H]inulin to parenchymal cells (1.4-fold) and non-parenchymal cells (11.8-fold). It is concluded that Tris-Gal-Chol incorporation into LDL leads to a markedly increased catabolism of LDL by the liver which might be used for lowering serum LDL levels. The possibility of increasing the interaction of LDL or liposomes with specific liver cell types by Tris-Gal-Chol might also have an application for targeting drugs or other compounds of interest to these cells. PMID- 2579072 TI - Immunochemical heterogeneity of human plasma high density lipoproteins. Identification with apolipoprotein A-I- and A-II-specific monoclonal antibodies. AB - Three mouse monoclonal antibodies specific for human apolipoprotein (apo) A-I and one specific for human apo-A-II were characterized with respect to their binding of high density lipoprotein (HDL) particles in solution. The apo-A-II-specific antibody bound 85% of 125I-HDL and 100% of soluble 125I-apo-A-II. However, none of the apo-A-I-specific antibodies bound greater than 60% of either HDL or soluble apo-A-I. Technical issues such as limiting amounts of antibody or antigen, radioiodination of the ligands, unavailability of the epitopes for reaction with antibody, selective binding of apo-A-I isoforms, and individual allotypic differences in apo-A-I were not responsible for the observed incomplete binding of all HDL and apo-A-I. The results suggested the existence of intrinsic immunochemical heterogeneity of apo-A-I both as organized on HDL as well as in free apo-A-I in solution. The validity of this observed heterogeneity was supported by demonstrating that (i) increased binding of HDL occurred when each of the apo-A-I antibodies was combined to form an oligoclonal antibody mixture, and (ii) 100% binding of HDL occurred when two apo-A-I antibodies were combined with the single apo-A-II antibody. To understand the basis for the heterogeneity of expression of apo-A-I epitopes on HDL, two hypotheses were examined. The first hypothesis that these apo-A-I antibodies distinguished apo-A-I molecules from different synthetic sources was not substantiated. Two of the antibodies bound epitopes on apo-A-I molecules in both thoracic duct lymph as an enriched source of intestinal HDL and the culture supernatants of the hepatic cell line Hep G2 as a source of hepatic HDL. The second hypothesis that the antibodies identified differences in the expression of apo-A-I on HDL subpopulations that were distinguished on the basis of size or net particle charge, i.e. organizational heterogeneity, appeared to provide the best available explanation for the immunochemical heterogeneity of apo-A-I in HDL. Relative differences in the expression of three distinct apo-A-I epitopes were demonstrated in HDL subpopulations obtained by either density gradient ultracentrifugation or chromatofocusing. In light of these studies, we conclude that there is intrinsic heterogeneity in the expression of intramolecular loci representing the apo-A-I epitopes identified by our monoclonal antibodies. Such heterogeneity must be considered in analysis of the biology and physiology of apo-A-I and lipoprotein particles bearing this chain. PMID- 2579073 TI - Conservation of human fibrinogen conformation after cleavage of the B beta chain NH2 terminus. AB - Human fibrinogen exposed to protease III from Crotalus atrox venom is cleaved near the NH2 terminus of the B beta chain yielding a species of Mr 325,000 (Fg325) with impaired thrombin clottability. The derivative was compared with intact fibrinogen in a number of ways to determine whether the functional defect resulted from a conformational change or from the loss of a polymerization site. NH2-terminal amino acid sequencing of isolated A alpha, B beta, and gamma chains showed that Fg325 contained intact A alpha and gamma chains, but differed from fibrinogen by the absence of the first 42 residues of the B beta chain. Fibrinopeptide A was present and was cleaved at the same rate in both fibrinogen and Fg325. The rate and extent of A alpha and gamma cross-linking by factor XIIIa was also indistinguishable. In contrast, the thrombin-catalyzed coagulation of Fg325 was 46% less in extent and 180-fold slower than observed for intact fibrinogen. A conformational comparison of Fg325 and fibrinogen was made using immunochemical and spectroscopic approaches. Antisera specific for different regions of the fibrinogen molecule were used to characterize the epitopes in Fg325. The only significant differences were found in the NH2-terminal region of the B beta chain, probed with antiserum to B beta 1-118. The conformational similarity of Fg325 and fibrinogen was confirmed by the identity of both near and far UV CD spectra of the two proteins. Structural, functional, and immunochemical results imply that cleavage of 42 NH2-terminal residues from the B beta chain is not accompanied by a measurable conformational change. The residues of this B beta chain segment, which are evidently located on the surface of the molecule, in conjunction with the NH2-terminal part of the A alpha chain appear to play an important role in the expression of a fibrin polymerization site. PMID- 2579074 TI - Phosphoproteins associated with the regulation of a specific potassium channel in the identified Aplysia neuron R15. AB - The neurotransmitter serotonin (5HT) activates a specific K+ conductance in the identified Aplysia neuron R15. This response to 5HT has been shown previously to be mediated by cAMP and cAMP-dependent protein phosphorylation. We have measured protein phosphorylation within neuron R15 in vivo, following the intracellular injection of [gamma-32P]ATP, and have demonstrated that 5HT modulates the phosphorylation of a number of proteins in R15. The present study was undertaken to determine which of these phosphoproteins are closely associated with, and may be responsible for, the K+ conductance increase. Treatment of neuron R15 with a cAMP analog produces some but not all of the 5HT-induced phosphoprotein changes, indicating that some are not cAMP-dependent and thus can be dissociated from the cAMP-dependent K+ conductance increase. Similar results are obtained by intracellular injection of the adenylate cyclase inhibitor guanosine 5'-O-(2 thiodiphosphate), which completely blocks the 5HT-evoked K+ conductance increase but fails to block some of the 5HT-induced phosphorylation changes. Examination of the phosphoprotein pattern at short times after 5HT application has demonstrated that some of the phosphoprotein changes, but not others, are closely associated in time with the appearance of the physiological response. These and other pharmacological and kinetic experiments have allowed the identification of two phosphoproteins, of Mr = 29,000 and 70,000, which cannot be dissociated from the 5HT-induced K+ conductance increase whatever the experimental manipulation. Thus, one or both of these phosphoproteins may be involved in the regulation of the 5HT-sensitive K+ channel in neuron R15. PMID- 2579075 TI - A regulatory calcium-binding site for calcium channel in isolated rat hepatocytes. AB - Loading isolated rat hepatocytes with high concentrations of the fluorescent Ca2+ chelator quin-2 in the absence of extracellular Ca2+ decreases by about 3-fold the cytosolic Ca2+ concentration ([Ca2+]i). In these low [Ca2+]i cells, the initial 45Ca2+ uptake rate, assumed to represent the Ca2+ influx, is stimulated to a level close to that promoted by maximal doses of vasopressin and angiotensin II in control cells. The subsequent addition of Ca2+ to the quin-2-loaded hepatocytes results in a rapid increase in [Ca2+]i and a return of Ca2+ influx towards the basal level usually observed in nonloaded cells. This indicates that the Ca2+ influx is dependent on [Ca2+]i but not on the quin-2 load itself. In the low [Ca2+]i cells, both the apparent Km and the apparent Vmax of the Ca2+ influx are increased as compared to the controls, indicating that the properties of the channels activated by lowering [Ca2+]i are apparently identical to those initiated by the hormones (Mauger, J.-P., Poggioli, J., Guesdon, F., and Claret, M. (1984) Biochem. J. 221, 121-127). It is proposed that in the isolated rat hepatocytes there is an inverse relationship between the Ca2+ influx and [Ca2+]i. Under resting conditions, [Ca2+]i might be high enough to partially inhibit the Ca2+ influx via a Ca2+ binding to an inhibitory site presumably located at the inner membrane surface. The role of the site in the hormonal action is discussed. PMID- 2579076 TI - Functional unit size of the neurotoxin receptors on the voltage-dependent sodium channel. AB - Radiation inactivation was used in situ to determine the functional unit sizes of the neurotoxin receptors of the voltage-dependent sodium channel from rat brain. Frozen or lyophilized synaptosomes were irradiated with high energy electrons generated by a linear accelerator and assayed for [3H]saxitoxin, 125I-Leiurus quinquestriatus quinquestriatus (alpha-scorpion toxin), 125I-Centruroides suffusus suffusus (beta-scorpion toxin), and batrachotoxinin-A 20 alpha [3H]benzoate binding activity. The functional unit size of the neurotoxin receptors determined in situ by target analysis are 220,000 for saxitoxin, 263,000 for alpha-scorpion toxin, and 45,000 for beta-scorpion toxin. Analysis of the inactivation curve for batrachotoxinin-A 20 alpha-benzoate binding to the channel yields two target sizes of Mr approximately 287,000 (50%) and approximately 51,000 (50%). The results are independent of the purity of the membrane preparation. Comparison of the radiation inactivation data with the protein composition of the rat brain sodium channel indicates that there are at least two functional components. PMID- 2579077 TI - Spacing of the -10 and -35 regions in the tac promoter. Effect on its in vivo activity. AB - In the tac promoter (deBoer, H. A., Comstock, L. J., and Vasser, M. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 21-25) the spacing between the -35 and -10 consensus sequences is 16 base pairs. Between these two regions we inserted 1 or 2 base pairs to increase the distance to 17 base pairs (trc promoter) or 18 base pairs (tic promoter). The activities of the three promoters were compared in vivo by fusion to the chloramphenicol acetyltransferase or to the Escherichia coli 4.5 S RNA gene. Both measurements gave consistent results. The trc and tic promoters are on average about 90% and 65% as active as the tac promoter, respectively. PMID- 2579078 TI - Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release, and histamine secretion in mast cells by islet-activating protein, pertussis toxin. A possible involvement of the toxin-specific substrate in the Ca2+-mobilizing receptor-mediated biosignaling system. AB - Incubation of rat mast cells with compound 48/80 resulted in transient breakdown of phosphatidylinositol 4,5-bisphosphate, rapid generation of inositol polyphosphates, 45Ca inflow, and the arachidonic acid liberation mainly from phosphatidylcholine, eventually leading to histamine secretion. All of these processes of signaling from Ca-mobilizing receptors to degranulation were markedly inhibited by prior 2-h exposure of cells to islet-activating protein (IAP), pertussis toxin. A23187 caused 45Ca inflow and releases of arachidonic acid and histamine without inducing breakdown of inositol phospholipids. The effects of A23187, in contrast to those of compound 48/80, were not altered by the exposure of cells to IAP. Incubation of the supernatant fraction of mast cell homogenates with the active component of IAP caused the transfer of the ADP ribosyl moiety of added [alpha-32P]NAD to a protein with Mr = 41,000. The IAP catalyzed ADP-ribosylation of this protein was prevented by guanosine 5'-(3-O thio)triphosphate, indicating that this IAP substrate resembles, in character, the alpha-subunit of the guanine nucleotide regulatory protein (Ni) involved in inhibition of adenylate cyclase. The degree of ADP-ribosylation of this IAP substrate was prevented progressively by pre-exposure of the homogenate-donor cells to increasing concentrations of IAP. The half-maximally effective concentrations of the toxin were 0.2 to 0.6 ng/ml for all the IAP-sensitive processes studied. Thus, the ADP-ribosylation of the Mr = 41,000 protein occurring during exposure of cells to IAP appears to be responsible for the inhibition of signaling observed. It is proposed that the alpha-subunit of Ni, or a like protein, mediates signal transduction arising from Ca-mobilizing receptors, probably prior to Ca2+ gating. PMID- 2579079 TI - Human triosephosphate isomerase cDNA and protein structure. Studies of triosephosphate isomerase deficiency in man. AB - Nine cDNA clones of human adult liver triosephosphate (TP) isomerase have been isolated and characterized. All nine appear to be derived from a single mRNA species. DNA sequencing of one clone, designated pHTPI-5a, defined the last two nucleotides of the methionine initiation codon, the entire 744-nucleotide coding region of the mature polypeptide, and the entire 448-nucleotide 3' untranslated region. The frequency of TP isomerase clones in the cDNA library suggests that TP isomerase mRNA is present in adult liver at approximately 25 copies/cell. A single, low abundance TP isomerase mRNA species was detected in RNA isolated from normal human fibroblast cell lines. Analysis of TP isomerase mRNA levels in cultured fibroblasts of individuals that are homozygous for TP isomerase deficiency revealed normal levels in one and approximately 40% of normal levels in another. From this small patient sampling, it can be concluded that the genetic basis for TP isomerase deficiency is heterogeneous. PMID- 2579080 TI - The structure of human platelet thrombospondin. AB - Two distinct murine monoclonal antibodies, designated MA-I and MA-II, and limited proteolysis with thrombin and trypsin have been used to probe the structure of human platelet thrombospondin. The results indicate that each of the constituent chains of thrombospondin comprise four distinct polypeptide segments. The production of these segments is influenced by the presence of calcium, the enzyme employed, the temperature of digestion, and the enzyme-to-substrate ratio. Thrombin digestion in the presence of calcium results in the release of a 30,000 dalton fragment, designated segment I, which contains the epitope for MA-II and the heparin-binding site. Prior EDTA treatment results in the concomitant cleavage of a 25,000-dalton fragment, designated segment IV, from the other terminus. Limited tryptic digestion in the absence of calcium produces a 47,000 dalton fragment (segment III) which is adjacent to segment IV. Segment III contains the epitope for MA-I. Segment II is an 85,000-dalton fragment which contains the interchain disulfide bonds. Calcium inhibits proteolysis at cleavage sites between segments II and III and between segments III and IV. In the presence of calcium, an 85,000-dalton fragment is produced, which is derived from portions of segments II, III, and possibly IV. Electron microscopy of platinum replicas produced by low angle rotary shadowing reveals that thrombospondin is composed of four well-defined globular regions connected by thin flexible regions. Three of the globular regions, designated globular region C, appear to be at the ends of the three thin connecting regions. The fourth globular region, designated globular region N, appears to be close to the site where the chains are cross-linked. Globular region N can be resolved into three separate smaller globular structures which are 70 +/- 7.1 A in diameter. This region is selectively removed by thrombin digestion in the presence of calcium and binds a monoclonal antibody directed against the heparin-binding peptides. These data indicate that globular region N comprises the three NH2-terminal portions (segment I) from each of the three chains of thrombospondin. Globular region C is located at the ends of each of the three thin connecting regions which are each approximately 291 +/- 46 A long. The removal of calcium results in a decrease in the size of globular region C from 118 +/- 18.6 A to 80 +/- 7.4 A and an increase in the length of the adjacent thin connecting region to 383 +/- 30 A.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2579081 TI - Changes in the nuclear and cytoplasmic levels of type I and type II collagen RNAs during growth of chondrocytes in 5-bromo-2'-deoxyuridine. AB - Chick embryo chondrocytes were grown in cell culture in the presence of 5-bromo 2'-deoxyuridine. Under these conditions, the cells attached to the tissue culture plates and became polygonal in shape and concurrently shifted their synthesis of collagen from type II to type I subunits. The changes in the levels of the corresponding collagen RNAs in the nucleus and cytoplasm were examined during this shift by dot blot and Northern blot analyses. It was found that the expression of the cartilage collagen gene, alpha 1(II), was controlled at the transcriptional level. While the type I collagen genes may also be partially controlled at the transcriptional level, both genes appear to be transcribed in chondrocyte nuclei although chondrocytes do not synthesize type I collagen. In these chondrocytes, the transcripts of the alpha 2(I) gene are polyadenylated and are apparently exported to the cytoplasm but are not translated. PMID- 2579082 TI - The cDNA cloning of a 55-kilodalton protein from guinea pig seminal vesicle. Evidence that the protein is the precursor of a 25-kilodalton basic secretory protein. AB - Guinea pig seminal vesicle epithelium synthesizes and secretes large amounts of four secretory proteins including a basic protein designated SVP-1. The latter migrates as a protein of 25 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When total cellular RNA from seminal vesicle epithelium was translated in vitro by a rabbit reticulocyte system, SVP-1 was not identifiable as a product. In contrast, a major product of the reticulocyte system was a 55 kDa protein which paradoxically could not be identified as one of the four known secretory proteins or as an abundant tissue protein. We isolated a cDNA clone which corresponded to the mRNA which coded for the 55-kDa protein. The mRNA was 1800 bases and of very high abundance; only the transcripts corresponding to the major secretory proteins SVP-3 and SVP-4 were as conspicuous. From these observations, we decided to test whether the 55-kDa protein was related to SVP-1. The 55-kDa protein was found to share properties of SVP-1, including an alkaline pI and selection by antibody against SVP-1. After proteolytic digestion of the 55 kDa protein, one fragment co-migrated with authentic SVP-1. Furthermore, detectable fragments of the 55-kDa protein smaller than SVP-1 all co-migrated with fragments generated from the proteolytic digestion of SVP-1. Finally, we show that the 55-kDa protein could be processed in vitro by seminal vesicle lumenal extracts to yield a 30-kDa protein and a protein the size of native SVP 1. The best explanation of our results is that the 55-kDa protein represents the primary translation product and precursor of SVP-1. Our proteolytic mapping and in vitro processing studies are consistent with the idea that the 55-kDa protein is a tandem repeat of two SVP-1 molecules. We used the cDNA clone to study the expression of the corresponding gene in different states of androgen depletion and repletion. PMID- 2579083 TI - Grading of bone tumors by analysis of nuclear DNA content using flow cytometry. AB - We studied 217 consecutive tumors of bone by flow cytometric analysis of nuclear DNA concentration after staining with propidium iodide. A diagnosis and histological grade (benign, low-grade, or high-grade sarcoma) were assigned to each tumor on the basis of staging data (with the exception of the forty-six giant-cell tumors, which, although indistinguishable histologically, were divided according to the flow cytometric pattern into two distinct groups), and we quantitatively studied the flow cytometry data to assess the percentages of cells in diploidy, tetraploidy, or aneuploidy. When compared, the mean values for the flow cytometric data for the three grades showed significant differences. Criteria were established for the three classes of tumors: for benign tumors, less than 11 per cent tetraploidy and no aneuploidy; for low-grade sarcomas, more than 11 per cent and less than 17 per cent tetraploidy, and no aneuploidy; and for high-grade tumors, either more than 17 per cent tetraploidy or aneuploidy. Tests for compliance for all groups of tumors (excluding the forty-six giant-cell tumors)--benign, low grade, or high grade--were significant for most of the benign lesions (with the exception of chondroblastoma and fibrous dysplasia) and for the high-grade sarcomas (with the exception of round-cell tumors). The low grade sarcomas did far less well, based principally on the failure of the low grade chondrosarcomas, chordomas, and adamantinomas to comply with the criteria. An attempt to assess the value of the system as a predictor of metastases showed that a low percentage of diploid cells (less than 75 per cent) and the presence of an aneuploid peak correlated statistically with the development of metastatic disease, but the usefulness of this observation could not be fully assessed because of multiple variables, associated principally with treatment. PMID- 2579084 TI - Altered patterns of keratin synthesis in human epidermal keratinocytes transformed by SV40. AB - Transformation of human epidermal keratinocytes by the oncogenic virus SV40 is a stage-specific process in which normal patterns of differentiation are progressively altered over time following infection. Within the context of this scheme, we examined the keratins produced by the infected cells. Immunofluorescence studies indicated that viral infection led to the formation of variant cells visibly lacking the normal keratin cytoskeleton after about 10-15 serial passages (60-90 cell generations) post infection. Analyses of variant cell formation in clonal populations grown on palladium islands revealed that the variants were derived within 2-3 cell divisions from cells containing an apparently normal keratin cytoskeleton, but that variant formation depended upon cell density. Immunoprecipitation of 35S-methionine labelled keratins from the infected keratinocytes revealed a gradual loss of the normal 46, 50, 56 and 58Kd keratin species over a period of many months after infection. The loss of the normal keratins was accompanied by the appearance of at least two species in the 48-52Kd size range not present in uninfected cells and the enhancement of a third, 40Kd, protein quite early after infection. Analysis of the altered keratin patterns on two-dimensional acrylamide gels using either isoelectric focusing (IEF) or non-equilibrium pH gradient electrophoresis (NEPHG) along the first dimension showed that the infected cells produced basic keratins which increased in relative abundance as cells became more transformed with serial passage including at least five isoelectric forms not seen in uninfected cells. Translation of poly A+ RNAs from the infected cells indicated that the altered keratin synthesis probably reflects changes in the translatable mRNA pool. PMID- 2579085 TI - A comparison of protein synthetic patterns of MDCK cells grown in serum and hormonally defined serum-free medium. AB - The development of hormonally defined serum-free media (HDM) for the culture of mammalian cells has allowed the study of specific cellular functions in a totally defined environment. Recently, several reports have indicated that there are differences in the basic cellular physiology of cells cultured in HDM when compared to cells cultured by the more traditional method of using serum supplemented culture media (SM). We report here that there are significant changes in the protein synthetic pattern in MDCK cells grown in HDM. There were no changes exhibited during the first passage in HDM, but following 10 passages in HDM there was an increased isotope ratio of 1) plasma membrane proteins with molecular weights of 12,000, 36,000 and 68,000 and 2) endoplasmic reticulum proteins with molecular weights of 12,000 and 37,000. Additionally, the incorporation of methionine and uridine were significantly increased in cells cultured in HDM for 10 passages. At present, we believe that these changes in the protein synthetic patterns are due at least partially to increased protein synthesis as indicated by monosome/polysome ratios. Therefore, though the use of HDM offers a completely defined system for studying cellular function, results obtained using HDM must be interpreted with caution when comparing them to previous studies that have used SM. PMID- 2579086 TI - Regulation of cell proliferation inhibitory and stimulatory factors diffused by 3T3 cultured cells. AB - The growth rate of normal cells multiplied in vitro decreases as the cell density of the culture increases. Previous results suggested that this density-dependent inhibition of growth in nontransformed cells was due to the diffusion of growth inhibitory substances in the medium of dense cultures. In this paper, we demonstrate that dense cultures of 3T3 cells secrete inhibitory and stimulatory factors. Macromolecules of conditioned medium were fractionated on Biogel P150 and the different fractions were tested on quiescent cultures of 3T3 cells stimulated or not to proliferate by addition of alpha globulin. When target cells were not stimulated to proliferate by addition of exocrine growth factors, we observed the inhibitory activity of a large molecular weight inhibitor (IDF45) and the stimulatory activity of autocrine growth factors (fraction about 35 and 10 K molecular weight), on the incorporation of 14C inosine into nucleotide pool and RNA. However, DNA synthesis was significantly stimulated with fraction 10 K only. This discrepancy between the stimulation of RNA and DNA synthesis may be explained by the presence, simultaneously, of inhibitory and stimulatory factors in fraction 35 and 10 K molecular weight. The presence of inhibitory factor was demonstrated when the fractions were tested on target cells stimulated to proliferate by alpha globulin addition and labeled with 14C thymidine. In these conditions, the stimulatory activity of autocrine growth factors was not observable, and only the inhibitory activity on DNA synthesis of fractions 35 and 10 K appeared. It is tempting to assume that the regulation of in vitro cell proliferation is determined by the balance between these antagonist stimulatory and inhibitory autocrine growth factors. PMID- 2579087 TI - Mechanism of the inhibitory action of dopamine and somatostatin on prolactin secretion from human lactotrophs in culture. AB - In an attempt to delineate the mechanism(s) of PRL secretion from human lactotrophs, the effects of dopamine and somatostatin on PRL release from adenomatous and nonadenomatous human pituitary cells in culture was studied. High K+ and the divalent cation ionophore A23187 both elevated PRL secretion, which was blocked by dopamine and somatostatin. When the cells were incubated in low calcium medium, PRL secretion was significantly inhibited. The addition of dopamine or somatostatin to low calcium medium further decreased PRL release. The stimulatory action of ionophore A23187 on PRL release was found even in the absence of extracellular calcium. Theophylline and isobutylmethylxanthine, when added to the incubation medium, increased PRL secretion, and dopamine as well as somatostatin again inhibited PRL release induced by phosphodiesterase inhibitors. No qualitative difference in these PRL responses was found in adenomatous and nonadenomatous human lactotrophs. In prolactinoma cells obtained from three different patients, cAMP generation was correlated with hormone release. Exposure of the cells to dopamine or somatostatin resulted in a parallel decrease in intracellular cAMP content and PRL secretion. The inhibitory effect of dopamine on PRL secretion and cAMP accumulation was blocked by coincubation of the cells with haloperidol. These results suggest that an increase in cytosol calcium caused by either mobilization from intracellular calcium pools or influx from the extracellular compartment and intracellular cAMP accumulation may be involved in the mechanism of PRL secretion from human lactotrophs, and dopamine and somatostatin may influence these two messengers to suppress PRL secretion. PMID- 2579088 TI - Somatomedin C-binding and action in fibroblasts from aged and progeric subjects. AB - Aging is associated with diminished cell growth, which has been ascribed in part to decreased cellular responsiveness to serum mitogens. To investigate whether there is an age-related loss of responsiveness to somatomedin-C (SM-C), we studied SM-C binding and action in early passage fibroblasts from normal donors, aged 7-96 yr, and one progeric subject. SM-C stimulated [3H]thymidine incorporation 4- to 16-fold in young cells, 4- to 17-fold in aged cells, and 4- to 11-fold in progeric cells. SM-C was synergistic with 0.25% human hypopituitary serum in stimulating [3H]thymidine incorporation in all cell lines. Dose-response curves for SM-C stimulation of thymidine incorporation were not significantly altered in aged or progeric cells. Half-maximal responses occurred at 5-15 ng/ml SM-C for all cell lines. [3H]Thymidine incorporation results were supported by cell replication studies. In addition, binding of [125I] SM-C was virtually identical in all cell lines, with 50% displacement at 2-5 ng/ml SM-C. Thus, in vivo aging does not appear to be associated with either an alteration in SM-C receptors or a diminished cellular responsiveness to SM-C's mitogenic effects. PMID- 2579090 TI - The origin of benign prostatic hyperplasia. PMID- 2579091 TI - Evaluation of Gonodecten for the presumptive diagnosis of gonococcal urethritis in men. AB - Gonodecten (Gd; U.S. Packaging Corp., LaPorte, Ind.) is a commercially available test for the presumptive diagnosis of gonococcal urethritis in men. With this test, urethral discharge is collected on a swab, placed in a plastic tube, and moistened with oxidase reagent. Development of a purple color on the swab within 3 min indicates the presence of gonococci. This system was compared with culture and Gram-stained smear for the diagnosis of gonorrhea. Of 240 specimens tested, 174 were positive with culture, Gram stain, and the Gd test and 48 were negative with all tests. For eight specimens, cultures and smears were positive, but the Gd test was negative. Nine specimens produced positive Gd tests with negative smears and cultures. Only one specimen was positive on culture and with the Gd test and negative on Gram-stained smear. Haemophilus species were isolated from 14 specimens; 5 produced positive Gd test reactions, with gonococci being coisolated from 4. The sensitivity and specificity of the Gd test compared with culture were 95.6 and 84.2%, respectively, whereas the Gram stain was 99.5% sensitive and 100% specific compared with culture. The Gd test may be a useful screening test for the diagnosis of gonorrhea in men with urethral discharge, particularly in settings where a microscope, Gram stain reagents, or technological expertise is not readily available. PMID- 2579089 TI - Serum levels of insulin-like growth factor (IGF) and IGF binding protein in insulin-dependent diabetics during an episode of severe metabolic decompensation and the recovery phase. AB - Serum insulin-like growth factor (IGF) and IGF-binding protein (IGF BP) levels were determined in 13 insulin-dependent diabetic patients (30-60 yr of age) during an episode of severe metabolic decompensation and the recovery phase. After separation by acidic gel filtration, the samples were assayed for IGF using a protein-binding assay (which measures mainly IGF I-related peptides) and for IGF BP by measuring the binding activity, in both assays using IGF I as tracer. The reference standard was a pool of normal adult serum with an assigned potency of 1 U IGF and 1 U IGF BP per ml. The mean IGF level in the uncontrolled state, 0.55 +/- 0.05 (SEM) U/ml, was about half that of normal subjects (1.03 +/- 0.03 U/ml, P less than 0.001). With treatment, IGF levels reached the normal range within 3 days. The pattern of changes in IGF BP levels was roughly similar, although the values in the uncontrolled state were less depressed (0.78 +/- 0.04 U/ml vs. 0.98 +/- 0.04 in normal subjects, P less than 0.01). Highly significant correlations (P less than 0.001) were found between IGF levels and the biological parameters reflecting control of the diabetes: glycosuria (r = -0.60), glycemia (r = -0.52), ketonemia (r = -0.65), and HCO3- (r = 0.58). Similar but less significant correlations were found for IGF BP. The mean GH level during the period of metabolic decompensation (9.0 +/- 1.5 ng/ml) was elevated compared to that after recovery (2.9 +/- 0.8 ng/ml) (P less than 0.025). There was a negative correlation between GH values and IGF levels (r = -0.67, P less than 0.001). The correlation with IGF BP was much less significant (r = -0.38, P less than 0.05). The results clearly reflect the role of insulin and nutritional factors in the control of IGF levels. They also support the notion that the biosynthesis of IGF and IGF BP is not regulated in the same way. PMID- 2579092 TI - Shared antigen between the myelin-associated glycoprotein (MAG) and a cell line from human T cell leukemia (HSB-2). AB - HSB-2 is a cell line originated from human T-cell leukemia and its membrane antigen is recognized by anti-HNK-1, a monoclonal antibody against human natural killer (NK) cells. Enzyme linked immunosorbent assay (ELISA) revealed that not only anti-HNK-1 but also rabbit polyclonal and human monoclonal anti-myelin associated glycoprotein (MAG) antibodies were absorbed by cell homogenate of HSB 2. Molt-4 and K-562 cell lines from human T-cell leukemia and human erythroleukemia did not absorb anti-HNK-1 and the anti-MAG antibodies. On the immunoblot of HSB-2 cell homogenate, two major molecules were stained by anti-HNK 1 and anti-MAG antibodies, while Molt-4 and K-562 were not stained by these antibodies. Comparing molecular weights of the two major molecules with those of MAG and derivative of MAG (dMAG), one is larger than MAG and the other is smaller than dMAG. The molecular weights of the two molecules were approximately 130 kDa and 80 kDa. The shared antigen in HSB-2 is not identical with MAG but a part of the molecule in the cells may be shared with a part of MAG molecule. PMID- 2579093 TI - Chronic-relapsing experimental autoimmune encephalomyelitis. Myelin basic protein induces suppression of blastogenesis during remissions but not during exacerbations. AB - Previous work from this laboratory has shown that resistance to acute experimental autoimmune encephalomyelitis (EAE) correlates with disease-specific, antigen-induced suppression of blastogenesis in vitro. We now report that this suppression in vitro also occurs during remissions in animals with chronic relapsing EAE. Hartley strain guinea pigs were injected with an homogenate of guinea pig spinal cord in complete Freund's adjuvant (CFA) to induce EAE or, for control purposes, with CFA alone. Animals injected with spinal cord homogenate developed EAE. Susceptible animals displayed up to 3 exacerbations over 4-5 months. Spleen cells and nervous tissue were sampled from different animals during and after each exacerbation. Gross examination of nervous tissue revealed plaques that at the light microscope level were characteristic of chronic relapsing EAE. Lymphocyte transformation assays using the T-cell mitogen concanavalin A (Con A), guinea pig myelin basic protein (BP), the purified protein derivative of M. tuberculosis (PPD) and histone proteins were conducted. Results of these assays showed that in spleen cells from animals sampled during remissions, BP suppressed the Con A response. Similar suppression was not observed with spleen cells from animals in exacerbation. This suppression depended upon the presence of adherent cells. Neither PPD nor histone proteins suppressed the Con A response. Thus, an immunologic mechanism, similar to that observed in Hartley guinea pigs resistant to acute EAE, is also found during remissions in the chronic-relapsing form of this disease suggesting that both resistance and remission are mediated by an antigen-induced suppressor mechanism. PMID- 2579094 TI - Immunocytochemistry of myelin basic proteins in adult rat oligodendroglia. AB - Immunocytochemical demonstration of myelin basic protein (MBP) in oligodendroglia of the developing rat and human central nervous system has been reported. However, reaction with MBP antiserum was detectable only prior to and during the early phase of myelination. The lack of reaction with still actively myelinating and mature oligodendroglia has been puzzling. We report here that by the use of mild fixation and by a modification of the staining technique previously used for detection of MBP on vibratome sections, staining of oligodendroglia in sections of adult rat brain has been achieved. PMID- 2579095 TI - Host genetic regulation of acute MHV-4 viral encephalomyelitis and acute experimental autoimmune encephalomyelitis in (BALB/cKe x SJL/J) recombinant inbred mice. AB - In the present report we provide the strain distribution patterns of susceptibility to acute mouse hepatitis virus type-4 (MHV-4) encephalomyelitis, acute experimental allergic encephalomyelitis (EAE) and vasoactive amine sensitivity (VAAS) for 9 (CXJ) recombinant-inbred strains between BALB/cKe (C) and SJL/J(J) mice. We confirm that susceptibility to MHV-4 is not linked to the H 2 complex, and that all strains susceptible to acute EAE have both a responder H 2 haplotype (H-2s or H-2d) and induced (B. pertussis) VAAS. In addition, we provide evidence that susceptibility to acute EAE induction is controlled by an additional presently unmapped locus and that an EAE-like histopathological disease does not usually follow MHV-4 infection intracerebrally in animals susceptible to MHV-4, acute EAE and induced VAAS. PMID- 2579096 TI - Dot immunobinding as a tool for the study of the CNS myelin antigen, M2. AB - The unidentified antigen M2, which is the target of demyelinating antibodies in sera from guinea pigs immunized with brain tissue, was studied using a dot immunobinding assay. This method is particularly appropriate for studying the immunologic properties of insoluble brain components such as myelin, glycolipids and myelin proteins. M2 was found to be a component of central nervous system myelin and not peripheral myelin. It appeared at the time of myelination, was not cerebroside or GM1 ganglioside and did not cross-react with the major myelin proteins, i.e. proteolipid or basic protein. These observations confirm and extend previous studies using a complement fixation assay for M2. The antigen was shown to be partially solubilized by Brij 35 and this detergent can provide a starting point for attempts at purification. PMID- 2579097 TI - Origins of anti-DNA autoantibodies. PMID- 2579098 TI - Mechanism of deoxyadenosine and 2-chlorodeoxyadenosine toxicity to nondividing human lymphocytes. AB - Deoxyadenosine has been implicated as the toxic metabolite causing profound lymphopenia in immunodeficient children with a genetic deficiency of adenosine deaminase (ADA), and in adults treated with the potent ADA inhibitor deoxycoformycin. However, the biochemical basis for deoxyadenosine toxicity toward lymphocytes remains controversial. The present experiments have examined in detail the sequential metabolic changes induced in nondividing human peripheral blood lymphocytes by incubation with deoxyadenosine plus deoxycoformycin, or with 2-chlorodeoxyadenosine (CdA), an ADA resistant deoxyadenosine congener with anti-leukemic and immunosuppressive properties. The lymphotoxic effect of deoxyadenosine and CdA required their phosphorylation, and was inhibited by deoxycytidine. As early as 4 h after exposure to the deoxynucleosides, strand breaks in lymphocyte DNA began to accumulate, and RNA synthesis decreased. These changes were followed by a significant fall in intracellular NAD levels at 8 h, a drop in ATP pools at 24 h, and cell death by 48 h. Incubation of the lymphocytes with 5 mM nicotinamide, a NAD precursor and an inhibitor of poly(ADP-ribose) synthetase, prevented NAD depletion. The nicotinamide treatment also rendered the lymphocytes highly resistant to deoxyadenosine and CdA toxicity, without altering dATP formation or the accumulation of DNA strand breaks. The poly(ADP-ribose) synthetase inhibitor 3 aminobenzamide exerted a similar although less potent effect. These results suggest that NAD depletion, probably triggered by poly(ADP-ribose) formation, is the principle cause of death in normal resting human lymphocytes exposed to deoxyadenosine plus deoxycoformycin, or to CdA. PMID- 2579102 TI - Delineation of children's behavior problems: a basis for assessment and intervention. PMID- 2579100 TI - 5-Azacytidine acts directly on both erythroid precursors and progenitors to increase production of fetal hemoglobin. AB - The effect of 5-azacytidine on erythroid precursors and progenitors was studied in nine patients with sickle cell anemia or severe thalassemia. Each patient received the drug intravenously for 5 or 7 d. 5-Azacytidine caused a four- to sixfold increase in gamma-messenger RNA concentration in bone marrow cells of eight of the nine patients and decreased the methylation frequency of a specific cytosine residue in the gamma-globin gene promoter in all nine patients. Within 2 d of the start of drug treatment there was a rise in the percentage of reticulocytes containing fetal hemoglobin (HbF; F-reticulocytes) without a significant change in the total number of reticulocytes, which suggested that there was a direct action of 5-azacytidine on erythroid precursors. Late erythroid progenitors (CFU-E), present in bone marrow after 2 d of drug administration, formed colonies containing an increased amount of HbF as compared with control colonies. Moreover, the number of CFU-E derived colonies was not decreased at these early times, which suggested that there was a direct action of 5-azacytidine on erythroid progenitors in the absence of cytotoxicity. Exposure of normal bone marrow cells in tissue culture to 5-azacytidine for 24 h reproduced both of these effects as judged during subsequent colony formation. The combined direct effects of 5-azacytidine on both the erythroid precursor and progenitor compartments resulted in an increase in HbF synthesis that was sustained for 2-3 wk. Toxicity to bone marrow as reflected by cytoreduction was evident after treatment in some patients but was not accompanied by an increase in HbF production. A correlation was found between the effects of 5-azacytidine on bone marrow, as assessed by in vitro measurements, and the hematological response of the individual patients to drug treatment. PMID- 2579099 TI - Vasoactive intestinal polypeptide-induced chloride secretion by a colonic epithelial cell line. Direct participation of a basolaterally localized Na+,K+,Cl cotransport system. AB - We have used a well-differentiated human colonic cell line, the T84 cell line, as a model system to study the pathways of cellular ion transport involved in vasoactive intestinal polypeptide (VIP)-induced chloride secretion. A modified Ussing chamber was used to study transepithelial Na+ and Cl- fluxes across confluent monolayer cultures of the T84 cells grown on permeable supports. In a manner analogous to isolated intestine, the addition of VIP caused an increase of net Cl- secretion which accounted for the increase in short circuit current (Isc). The effect of VIP on Isc was dose dependent with a threshold stimulation at 10(-10) M VIP, and a maximal effect at 10(-8) M. Bumetanide prevented or reversed the response to VIP. Inhibition by bumetanide occurred promptly when it was added to the serosal, but not to the mucosal bathing media. Ion replacement studies demonstrated that the response to VIP required the simultaneous presence of Na+, K+, and Cl- in the serosal media. Utilizing cellular ion uptake techniques, we describe an interdependence of bumetanide-sensitive 22Na+, 86Rb+, and 36Cl- uptake, which is indicative of a Na+,K+,Cl- cotransport system in this cell line. This transport pathway was localized to the basolateral membrane. Extrapolated initial velocities of uptake for each of the three ions was consistent with the electroneutral cotransport of 1 Na+:1 K+ (Rb+):2 Cl-. Our findings indicate that VIP-induced Cl- secretion intimately involves a bumetanide sensitive Na+,K+,Cl- cotransport system which is functionally localized to the basolateral membrane. PMID- 2579103 TI - Comprehensive health services for developmentally disabled Navajo children. AB - A retrospective study of 60 Navajo children with developmental disabilities was conducted to evaluate the quality and comprehensiveness of health services provided. Descriptive analysis by a multidisciplinary panel included medical record reviews, family interviews, and site visits to local health, educational, and family support services. Findings included timely and appropriate management of "medical" problems but a general neglect of "developmental" issues, such as hearing, speech/language, cognitive, and behavioral functioning, and attention to family understanding and adjustment toward caring for a handicapped child. Primary prevention and screening efforts were judged generally adequate, although not utilized by the majority of mothers of disabled children. Diagnostic assessments, family counseling, and referrals for treatment were incomplete, fragmented, and poorly coordinated. These problems resulted in potentially harmful delays in making referrals to available treatment programs. The majority of families interviewed tended to focus on the "medical" problems, had a poor understanding of the "developmental" components, and rarely participated actively in treatment. PMID- 2579101 TI - Human macrophage activation. Modulation of mannosyl, fucosyl receptor activity in vitro by lymphokines, gamma and alpha interferons, and dexamethasone. AB - We describe a sensitive assay to measure immune activation of human macrophages in cell culture. Freshly isolated blood monocytes from normal subjects lack the ability to endocytose and degrade mannosyl-terminated glycoconjugates via specific receptors, but acquired this activity after cultivation in autologous serum for approximately 3 d. Addition of specific antigen, purified protein derivative, or T cell mitogens to mononuclear cells prevented the appearance of macrophage mannosyl receptor activity and lymphokine, gamma-, and alpha interferons selectively down-regulated receptor activity in monocyte-macrophage targets. The effects of antigen challenge and gamma-interferon on mannosyl receptors can be prevented by 10(-8) M dexamethasone. Dexamethasone also inhibited release of another macrophage activation marker, plasminogen activator, which was increased by both gamma- and alpha-interferons. These studies show that activation of human macrophages is regulated by opposing actions of lymphokines and glucocorticoids. PMID- 2579104 TI - Granulocyte and monocyte surface membrane markers in the myelodysplastic syndromes. AB - The expression of lineage specific surface antigens on granulocytes and monocytes was quantitated using monoclonal antibodies in 16 healthy adults and 21 patients with myelodysplastic syndromes. In nine of 19 patients the granulocytes showed a decrease in myeloid or an increase in monocyte antigen expression or both. In 11 of 19 patients the monocytes showed a decreased expression of monocyte antigens or an increase in myeloid antigens or both. The data suggest that in the myelodysplastic syndromes the granulocyte-macrophage progenitors do not develop along two divergent lines but differentiate with the emergence of dual characteristics. PMID- 2579105 TI - Blood group antigens A, B, H, Lea, Leb, and I(Ma) in resting and tetragastrin stimulated gastric juice of patients with non-neoplastic diseases of the stomach. AB - In view of the anomalous expression of blood group and related antigens in the gastric mucosae of patients with malignant and premalignant diseases of the stomach, and the potential clinical value of their measurement, a preliminary study has been performed on the blood group antigens A, B, H, Lea, Leb, and I(Ma) in glycoprotein rich extracts of the resting and tetragastrin stimulated gastric juice of patients without evidence of gastric cancer. The aim has been to assess whether the antigenic profiles known to distinguish the gastric mucosae of secretors from those of non-secretors are reflected in the glycoproteins of gastric juice. Antigenic profiles which distinguish secretors from non-secretors were observed in the stimulated rather than the resting gastric juice as follows: the A, B or H antigens but not I(Ma) were strongly expressed in the glycoproteins of secretors, while I(Ma) was the antigen characteristic of non-secretors. On the other hand, there was considerable overlap in the Lea and Leb antigen values in the resting and stimulated gastric juice of secretors and non-secretors. Among these antigens, I(Ma) is known to appear as a neo-antigen in the gastric mucosae of secretors with malignant and premalignant diseases of the stomach. Thus this antigenic determinant is potentially a clinically useful marker in the gastric juice of 75% of the population who are secretors. The clinical value of the levels of this antigen in the gastric juice now deserves investigation. PMID- 2579106 TI - Hypopharyngeal squamous cell carcinoma metastatic to skin. AB - Multiple cutaneous nodules developed in a patient with squamous cell carcinoma of the hypopharynx. Biopsy revealed poorly differentiated squamous cell carcinoma metastatic to the skin. A keratin stain confirmed the presence of keratin in the cutaneous tumor cells. Cutaneous metastases from carcinoma of the hypopharynx are very rare. PMID- 2579107 TI - Estrogen and progesterone receptors in congenital melanocytic nevi. AB - Using fluorescent-labeled estrogen and progesterone, congenital nevi from fifteen patients, six male and 9 female, were studied for the presence of corresponding cytoplasmic receptor binding. Similar studies were done in a control population of twenty-one patients, ten male and 11 female, with acquired intradermal nevi. Congenital nevi contained high concentrations of estrogen-binding and progesterone-binding nevus cells in both male (6/6) and female patients (5/9). Lesser concentrations of estrogen-binding and progesterone-binding nevus cells were found in congenital nevi from the remaining four female patients. In contrast, acquired intradermal nevi from the control group of patients had little or no detectable estrogen or progesterone binding. These data indicate that congenital nevi are similar in hormonal-binding properties to melanomas and dysplastic nevi, in contrast to acquired intradermal nevi. PMID- 2579108 TI - Histologic diagnosis of benign adnexal skin tumors. An algorithmic approach. AB - Adnexal lesions have traditionally been classified according to their histogenesis. Frequently this approach is not particularly helpful in the initial evaluation of these lesions. A diagnostic algoithm based on morphologic characteristics alone provides a more orderly and logical approach to their diagnosis. PMID- 2579109 TI - Vascular lesions in pregnancy; a hypothesis. PMID- 2579110 TI - Cutaneous wound healing: a model for cell-matrix interactions. AB - Molecules of the extracellular matrix may influence the biologic behavior of basal cell keratinocytes. In the unwounded situation, basal cells are in contact with the basement membrane of the dermo-epidermal junction and eventually detach from this structure, move vertically, and differentiate. During wound healing these cells are in contact with an entirely different set of matrix molecules (including elastin, fibronectin, and interstitial collagen). The cells migrate laterally to cover the wound and remain in a proliferative, undifferentiated state. When 25-day-old epidermal cultures were compared, adult human keratinocyte migration across an interstitial collagen matrix was found to be approximately double that across a basement membrane matrix. This finding suggests that adult human keratinocyte migration is influenced by the matrix in contact with the cells. This type of cell-matrix interaction may be important to the understanding of cutaneous wound healing. PMID- 2579111 TI - A study of intermediate filaments (cytokeratin, vimentin, neurofilament) in two cases of Merkel cell tumor. AB - In two cases of Merkel cell tumor, the study of intermediate filaments, using monoclonal antibodies (vimentin, cytokeratin, neurofilaments), confirmed the double differentiation (neuroendocrine and epithelial) of this tumor as previously observed in histological, electron microscopical and histochemical analyses. Labelling of the tumor cells was positive with monoclonal antibodies against neurofilament proteins and cytokeratin. PMID- 2579112 TI - Correlative studies of Verruca vulgaris by H & E, PAP immunostaining, and electronmicroscopy. AB - Twenty-one specimens of Verruca vulgaris were used for an investigation to define what portion of the papillomatous structures seen in H & E stain will correspond to the areas of positive staining for papilloma virus antigen utilizing the peroxidase-antiperoxidase immunostaining technique. Vacuolar spaces filled with thready material and large ovoid parakeratotic cells seen in H & E stain stained positively for papilloma virus antigen. In the granular layer, viral antigens stained heavily, the nuclei of cells showing koilocytosis. Both round and irregularly shaped kerathohyaline granules did not stain positively for viral antigen stain. Eight of the 21 specimens showed marked positivity for papilloma virus antigen. Three other cases were positive in only focal sites. Of the 8 immunostained-positive selected cases used for ultrastructural studies, only 2 showed the viral particles. The study suggests that the PAP immunostaining is a more sensitive and yet less cumbersome method than electronmicroscopy for demonstration of papilloma virus. PMID- 2579113 TI - Alpha tocopherol alters the distribution of Langerhans cells in DMBA-treated hamster cheek pouch epithelium. AB - Thirty-seven adult male and female golden hamsters (Mesocricetus auratus) were divided into four experimental groups. In Group A, the animals served as untreated controls, having the left buccal pouches painted with mineral oil. In Group B, the animals received 10 mg vitamin E (alpha tocopherol) in peanut oil by the oral route, with a fine pipette, twice weekly. In Group C animals, the left buccal pouch was painted three times weekly with DMBA (0.5% solution of 7,12 dimethylbenz(a)anthracene in heavy mineral oil). Group D animals received both vitamin E and DMBA in the amounts indicated for Groups B and C, with the vitamin E being administered on days alternate to the DMBA painting, also in the manner described for the above groups. All animals were killed after eight weeks of treatment. Epithelial whole mounts were prepared from the left buccal pouches. These specimens were then stained for ATPase to demonstrate the presence of Langerhans cells (LCs). A notably decreased density of LCs was observed after treatment with DMBA. Vitamin E administration in addition to DMBA treatment resulted in a less dramatic decrease in LC density. Since vitamin E has been shown to retard experimental oral carcinogenesis, vitamin E may retard carcinogenesis by maintaining the number of Langerhans cells. PMID- 2579115 TI - Microenvironmental and total exposures to carbon monoxide for three population subgroups. PMID- 2579114 TI - Reduction of acidurance of streptococcal growth and glycolysis by fluoride and gramicidin. AB - The acidurance of glycolysis by intact cells of Streptococcus mutans GS-5, Streptococcus salivarius ATCC 25925, and Streptococcus sanguis NCTC 10904 was found to be highly dependent on membrane functions affected by gramicidin, which increases the proton permeability of cell membranes. Plots of % glucose utilized during two hours against suspension pH values for cells suspended in 100 mM phosphate buffer plus 1 mM MgCl2 plus 13.9 mM glucose indicated, for 50% glucose utilization, pH values of 5.0 for S. mutans, 5.7 for S. salivarius, and 6.2 for S. sanguis. Gramicidin treatment shifted these values to 6.0, 6.3, and 6.9, respectively. Growth of S. mutans and S. salivarius in complex media proved to be more acid-sensitive than was glycolysis, and in batch cultures, there was a well defined, post-growth phase of glycolysis. Minimum pH values for growth and for glycolysis in medium with excess glucose were approximately 4.8 and 4.4, respectively, for S. mutans, and 4.9 and 4.3 for S. salivarius. S. sanguis was less aciduric and showed little differential acid sensitivity, with minimum pH values of about 5.2 for both growth and glycolysis. Fluoride acted to eliminate the differences in acidurance of growth and glycolysis for S. mutans or S. salivarius and to render both processes more acid-sensitive. Thus, glycolysis was more fluoride-sensitive than was growth. Growth was found to be acid-limited in media with initial glucose levels greater than 0.2, 0.3, and 0.5% (weight/volume) for S. sanguis, S. mutans, and S. salivarius, respectively, and to be glucose limited at lower levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579116 TI - Leukocyte histamine release to suxamethonium in patients with adverse reactions to muscle relaxants. AB - In an earlier study we confirmed the usefulness of intradermal skin tests and histamine release in diagnosis of patients reactive to muscle relaxants, and we suggested an IgE-mediated reaction rather than an idiosyncratic mechanism. In a later study, we studied the relationship between (Formula: see text) that is one of the muscle relaxants producing the most frequent adverse reactions under anesthesia. Histamine release was measured in five patients with increasing concentrations of suxamethonium in the presence or absence of human serum albumin in Tris buffer. Suxamethonium by itself without any carrier in the buffer could, in vitro, act as a true allergen on target leukocytes in the sensitized patients' group. Acetylcholine (20 and 200 micrograms/ml) did not induce significant histamine release in five patients with positive histamine release in the presence of suxamethonium. Preincubation of leukocytes from 11 patients for 30 min with 20 and 200 micrograms of acetylcholine in Tris albumin CA++ Mg++ buffer decreased the histamine release induced by suxamethonium (10 micrograms/ml); mean maximal histamine release of 46% +/- 4.2 was reduced to 31.4 +/- 5.8 and 7% +/- 4 (p less than 0.001), respectively. However, in eight control subjects similar concentrations of acetylcholine did not change the maximal histamine release induced by anti-IgE (0.2 micrograms/ml). In the same way acetylcholine did not modify histamine release induced by Dermatophagoides pteronyssinus extract (1/10,000 w/v) in six patients allergic to this allergen. This study suggests that suxamethonium acts as a true allergen and that acetylcholine or one of its metabolites may act as a hapten inhibitor in the model of histamine release induced by suxamethonium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579117 TI - Induction of antigen-specific suppressor cells in patients with hay fever receiving immunotherapy. AB - In order to evaluate the effect of immunotherapy on subpopulations of lymphocytes, peripheral blood mononuclear cells were fractionated into T and non T cells by incubating in anti-immunoglobulin-coated plates. T cells were further fractionated into rye grass antigen-adherent and nonadherent fractions and human serum albumin (HSA)-adherent and nonadherent fractions by incubating in rye grass antigen-coated and HSA-coated plates, respectively. The mean rye antigen stimulated proliferative response of rye antigen-adherent fraction was significantly lower than that of rye antigen-nonadherent fraction in patients with rye grass hay fever receiving immunotherapy. There was no difference in the rye antigen-stimulated proliferative response between the HSA-adherent and nonadherent fractions. Both the rye antigen-adherent and nonadherent fractions proliferated similarly when they were stimulated by an unrelated antigen, Candida albicans. The rye antigen-stimulated proliferative response of rye antigen nonadherent cells could be suppressed by coculturing with rye antigen-adherent cells from patients receiving immunotherapy. Furthermore, the treatment of cocultures with monoclonal antibody against suppressor-cytotoxic T cell (OKT8) subpopulation and guinea pig serum complement reversed the suppression. In patients receiving no immunotherapy, there was no difference in the rye grass antigen-stimulated proliferative response between the rye antigen-adherent and nonadherent fractions. These results suggest that immunotherapy induces a subpopulation of T cells that are adherent to antigen-coated plates and are capable of suppressing T cell proliferation stimulated by the specific antigen. PMID- 2579118 TI - Obstructive hydrocephalus secondary to giant cerebral aneurysm in the elderly: two case reports of functional improvement after ventricular shunting. PMID- 2579120 TI - Immunocytochemical localization of cathepsin D in lysosomes of cortical collecting tubule cells of the rat kidney. AB - Immunocytochemical localization of cathepsin D in rat renal tubules was investigated by means of indirect immunoenzyme and protein A--gold techniques. By light microscopy, fine granular staining was seen in the mesangial cells of glomeruli. Heavy reaction deposits were present in the cortical tubular segments and some of the medullary collecting tubules. The proximal tubules contained a few positive granules. Other segments were negative for cathepsin D. By electron microscopy, gold particles representing the antigenic sites for cathepsin D were present in cytoplasmic granules and multivesicular bodies of the segment of the cortical collecting tubule. These cytoplasmic granules were presumed to be digestive vacuoles (secondary lysosomes) from their morphological profile. The proximal tubule cells contained the very weakly labeled secondary lysosomes. No specific labeling was noted in other segments of the nephron. Control experiments confirmed the specificity of the immunostaining. Quantitative analysis of the labeling density in each subcellular compartment also confirmed that the main subcellular sites for cathepsin D are the secondary lysosomes and multivesicular bodies. The labeling density in these granules of the lysosomal system varied widely with the individual granules, suggesting that there is a considerable heterogeneity of enzyme content among the granules of the lysosomal system. The prominent presence of cathepsin D in the cortical collecting tubule suggests a certain segment-specific function of this proteinase. PMID- 2579119 TI - Double immunocytochemical staining in the study of antibody-producing cells in vivo. Combined detection of antigen specificity (anti-TNP) and (sub)class of intracellular antibodies. AB - Mice and rabbits were immunized with trinitrophenyl (TNP)-conjugated keyhole limpet hemocyanin (KLH). Cells producing specific antibodies against the hapten TNP were detected in vivo in spleen and lymph nodes using a TNP--alkaline phosphatase (AP) conjugate. Using horseradish peroxidase (HRP)-conjugated anti mouse (sub)class (IgG2A, IgG2B, IgM) antibodies and anti-rabbit class (IgG, IgM) antibodies and a double immunocytochemical staining technique for simultaneous demonstration of the enzymes AP and HRP, we were able to determine both the antigen specificity (anti-TNP) and the (sub)class of intracellular antibodies produced by individual antibody-forming cells in vivo. PMID- 2579121 TI - Monoclonal antibodies against rat saliva and salivary gland antigens. AB - Hybridomas were produced by the fusion of NS1 myeloma cells with spleen cells of a BALB/c mouse immunized with rat submandibular saliva. Growth of hybridomas was evident in 60/96 wells, and colonies secreting antibodies against saliva components were identified in 20 wells by using a solid phase enzyme-linked immunoassay. Cloning of cells from 12 wells yielded originally 43 hybridoma cell lines secreting anti-saliva antibodies. After recloning, one hybridoma (4Cl3) was selected for further studies. The hybridoma (4Cl3) cells were grown as ascites tumors, and the antibodies were purified from the ascitic fluid by diethylaminoethyl Affi-gel Blue chromatography. The purified antibody (MA4), immunoglobulin G1, immunoprecipitated a 39K dalton protein from submandibular saliva, and also reacted with a protein of the same electrophoretic mobility on immunoblots. From extracts of submandibular gland slices, incubated with [3H]leucine, the antibody again immunoprecipitated a 39K protein, indicating that this protein is synthesized in the gland. MA4 was used for immunocytochemical stainings of submandibular glands of rats of different ages. In general, immunostaining was seen only in acinar cells. Thus, there was no staining in the glands of 1-day-old rats that lack differentiated acinar cells. In the glands of 1- to 4-week-old rats the number of immunoreactive cells and the extent of immunostaining paralleled the differentiation of the acinar cells. In the glands of adult rats a uniform staining of the secretory granules of the acinar cells was observed. The immunoreactive 39K protein seemed to be restricted to the acinar cells in the submandibular gland; there was no immunostaining in the parotid, sublingual, or lingual salivary glands, or in the pancreas, colon, and duodenum. Stimulation of saliva secretion by isoproterenol resulted in a virtual depletion of the antigen from the acinar cells. These results indicate the feasibility of producing mouse hybridomas that secrete antibodies against rat saliva components. The monoclonal antibody at hand will be useful in analyzing the differentiation of the acinar cells, and the factors that influence this differentiation process. PMID- 2579122 TI - Silver amplification of mercury sulfide and selenide: a histochemical method for light and electron microscopic localization of mercury in tissue. AB - A method for light and electron microscopic demonstration of mercury sulfides and mercury selenides in mammalian tissue is presented. Silver ions adhering to the surface of submicroscopic traces of mercury sulfides or selenides in the tissue are reduced to metallic silver by hydroquinone. Physical development thereupon renders deposits of mercury sulfides or mercury selenide visible as spheres of solid silver. Examples of localization of mercury in the central nervous system and various organs from animals exposed to mercury chloride or methyl mercury chloride with or without additional sodium selenide treatment are presented. Selenium treatment results in a considerable increase in the amount of mercury that can be made visible by silver amplification. After mercury chloride treatment, most of the mercury is localized in lysosomes and is only rarely seen in secretory granules. After simultaneous selenium treatment, mercury is also found in nuclei of proximal tubule cells in the kidney and in macrophages. The "sulfide-osmium" method for ultrastructural localization of mercury suggested by Silberberg, Lawrence, and Leider (Arch Environ Health 19:7, 1969) and the light microscopic method using a photographic emulsion suggested by Umeda, Saito, and Saito (Jpn J Exp Med 39:17, 1969) have been experimentally analyzed and commented on. PMID- 2579123 TI - Antisera to gamma-aminobutyric acid. II. Immunocytochemical application to the central nervous system. AB - An antiserum to gamma-aminobutyric acid (GABA) was tested for the localization of GABAergic neurons in the central nervous system using the unlabeled antibody enzyme method under pre- and postembedding conditions. GABA immunostaining was compared with glutamate decarboxylase (GAD) immunoreactivity in the cerebellar cortex and in normal and colchicine-injected neocortex and hippocampus of cat. The types, distribution, and proportion of neurons and nerve terminals stained with either sera showed good agreement in all areas. Colchicine treatment had little effect on the density of GABA-immunoreactive cells but increased the number of GAD-positive cells to the level of GABA-positive neurons in normal tissue. GABA immunoreactivity was abolished by solid phase adsorption to GABA and it was attenuated by adsorption to beta-alanine or gamma-amino-beta hydroxybutyric acid, but without selective loss of immunostaining. Reactivity was not affected by adsorption to glutamate, aspartate, taurine, glycine, cholecystokinin, or bovine serum albumin. The concentration (0.05-2.5%) of glutaraldehyde in the fixative was not critical. The antiserum allows the demonstration of immunoreactive GABA in neurons containing other neuroactive substances; cholecystokinin and GABA immunoreactivities have been shown in the same neurons of the hippocampus. In conclusion, antisera to GABA are good markers for the localization of GABAergic neuronal circuits. PMID- 2579124 TI - Antisera to gamma-aminobutyric acid. III. Demonstration of GABA in Golgi impregnated neurons and in conventional electron microscopic sections of cat striate cortex. AB - Two methods are described for the immunocytochemical demonstration of immunoreactive gamma-aminobutyric acid (GABA) in the visual cortex of the cat, an area that contains several types of GABAergic neurons and requires combined methods for their characterization. The first method is illustrated by a representative example of a Golgi-impregnated and gold-toned interneuron of the "bitufted" type situated in layer VI and having an ascending axon. After recording the three-dimensional features of the cell, semithin (0.5 micron) sections of the perikaryon were cut and GABA was demonstrated in the cell body by the unlabeled antibody enzyme method. While immunocytochemistry was used to determine the probable transmitter of the neuron, Golgi-impregnation of the same cell was used to identify its neuronal type. Since aldehyde-osmium fixation was used, further electron microscopic (EM) analysis of the neuron's synaptic connections was possible. The second procedure demonstrated GABA in EM sections of aldehyde-osmium-fixed cortex using protein A-gold as an immunocytochemical marker. Immunoreactivity was found in certain neurons, dendrites, axons, and boutons forming type II synaptic contacts that from previous studies have been thought to be GABAergic. Thus ultrastructural analysis using optimal conditions can now be supplemented with the identification of the transmitter in the same section. PMID- 2579125 TI - The immunobiology of the T cell response to Mls-locus-disparate stimulator cells. I. Unidirectionality, new strain combinations, and the role of Ia antigens. AB - The primary mixed lymphocyte reaction of T cells to Mls-locus-disparate stimulator cells differs from that to non-self Ia antigens in several respects. In the present experiments, the unidirectional nature of this response is shown in several strain combinations, including the newly detected Mlsa and Mlsa-like alleles expressed by strains PL/J, RF/J, and SM/J. All of these strains stimulate MHC-identical T cells strongly. In addition, they stimulate a variety of cloned T cell lines specific for Mlsa,d, which can thus be shown to respond to Mlsa,d stimulators of the H-2b,d,k,u, and v haplotypes. Although these results suggest that primary T cell responses to Mlsa,d are unlikely to be MHC restricted, these primary responses are readily inhibited by monoclonal antibodies specific for the I-A and especially the I-E products borne by the stimulator cells, as well as by monoclonal antibodies specific for L3T4a on the responding T cells. This effect of anti-Ia antibodies is not overcome by exogenous interleukin 1. Thus, I-A and especially I-E molecules are centrally involved in the unidirectional primary T cell response to the potently stimulating Mlsa and Mlsd alleles expressed by cells of several different MHC haplotypes. PMID- 2579126 TI - The immunobiology of T cell responses to Mls-locus-disparate stimulator cells. II. Effects of Mls-locus-disparate stimulator cells on cloned, protein antigen specific, Ia-restricted T cell lines. AB - Cloned, protein antigen-specific, Ia-restricted T cell lines frequently (approximately 20%) also respond strongly to stimulator cells from strains expressing stimulatory alleles at the chromosome 1-encoded Mls-locus. Furthermore, such responses are blocked by monoclonal antibodies specific for Ia antigens expressed by the stimulator rather than the responder cells. However, such responses show no specificity for polymorphic determinants on Ia molecules, although in such responses, as in primary and secondary T cell responses to stimulating Mls-locus alleles, I-E molecules appear to play a central role. These results, combined with the unique immunobiology of the primary T cell proliferative response to Mls-locus-disparate stimulator cells, suggest to us that this response involves the interaction of the receptor on T cells for antigen:self Ia with a relatively nonpolymorphic region of Ia glycoproteins. This hypothesis is supported by the observation that a monoclonal antibody to the T cell receptor will inhibit both responses, although the response to Mls-locus disparate stimulators appears to be more sensitive to these antibodies. We propose that the interaction of the T cell receptor with Ia is stabilized by a cell interaction molecule encoded or regulated by the Mls-locus gene product permitting the T cell receptor:Ia glycoprotein interaction to lead to T cell activation. PMID- 2579127 TI - T cell responses to Mls determinants are restricted by cross-reactive MHC determinants. AB - The studies presented here investigated the relationship between T cell recognition of MHC-encoded products and non-MHC-linked Mls determinants. The first aspect addressed whether Mls-reactive T cells recognize Mls-encoded products alone or in association with MHC-encoded determinants. Initial studies used Mlsa-specific T cell clones that were generated by repeated stimulation of C57BL/6 or B10.A(5R) spleen cells with DBA/2 lymphoid cells. These clones recognized Mlsa on cells expressing MHC products of the H-2b, H-2d, and H-2k haplotypes, but not the H-2q haplotype. Thus, these cloned T cells were found to recognize Mlsa products in association with public but demonstrably polymorphic H 2 determinants. The question of whether T cell clones that were specific for self H-2 determinants (autoreactive) or soluble antigen plus syngeneic H-2 (antigen specific) could also be stimulated by Mlsa determinants was also addressed. A substantial proportion of the antigen-specific or autoreactive T cell clones tested were stimulated by Mlsa determinants. Furthermore, stimulation of these clones by Mlsa was H-2 restricted. The pattern of H-2-restricted recognition of Mlsa by these clones was not distinguishable from that observed in the Mlsa specific T cell clones, nor was it influenced by the primary specificity or H-2 restriction pattern of a given clone. Although these findings provide a means of explaining the observation that Mls-reactive T cells exist at extremely high precursor frequencies, they also raise questions regarding the nature of the receptor structures which are used by a single T cell in the recognition of two or more apparently distinct stimuli. PMID- 2579128 TI - Dextran augments delayed-type hypersensitivity by interrupting one limb of the suppressor cascade. AB - We have studied the immunomodulatory effect of dextran on the development of delayed-type contact hypersensitivity to a hapten in mice. Administration of an optimal dose of dextran 2 hours before applying picryl chloride to abdominal skin caused a twofold rise in the level of hapten-specific DTH. A study of the kinetics of development of DTH under the influence of dextran showed that comparable levels of response could be seen 2 days earlier in treated than in untreated mice, i.e., on the third day in contrast to the fifth day after sensitization. The peak of the responses, while greater in dextran-treated mice than in normal controls, remained the same at 5 days. Adoptive transfer studies revealed that comparable levels of DTH were conferred upon recipient mice by half the number of splenic cells from dextran-treated mice than that required from normal sensitized mice. Because several suppressor mechanisms are known to down regulate DTH, we have studied dextran's effect on the neutralization of these systems as a possible explanation for its enhancing capabilities. Detailed examination was made of dextran's effect on the two suppressor T cells, Ts1 and Ts3, that act in tandem as well as its effect on the Ts1 and macrophage that work in combination. Both systems depress the efferent limb of DTH. We have found that dextran blocks the Ts1-macrophage pathway that controls DTH. Ts1 was found to arise normally in mice pretreated with dextran. Furthermore, Ts1 from dextran treated mice produced TsF1 normally. However, we have found that dextran interferes with the production of macrophage suppressor factor (M phi-SF). Interference was partial when dextran was introduced during the interval in which macrophages were being armed with TsF1, and it was complete when dextran was put with pre-armed macrophages before they were triggered with antigen for production of M phi-SF. On the other hand, the Ts1-Ts3 limb of suppression remained unaffected by exposure to the immunomodulator. We found Ts3 arose normally in hapten-sensitized mice that had been pretreated with dextran. In addition, Ts3 became armed with TsF1 in vitro in the presence of dextran since the cells functioned properly to suppress mature DTH effector cells. Finally, TsF3 was able to act in vitro upon DTH effector cells despite the presence of dextran.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2579129 TI - Suppression of alloimmune cytotoxic T lymphocyte (CTL) generation by depletion of NK cells and restoration by interferon and/or interleukin 2. AB - By using rabbit antiserum to a glycolipid, ganglio-n-tetraosylceramide (ASGM1), the accessory effect of natural killer (NK) cells on the generation of alloimmune CTL in mice was investigated. When normal C3H/He mice were immunized with C57BL/6 or BALB/c spleen cells, they generated alloimmune CTL with a surface marker phenotype of Thy-1+ Lyt-1-2+ ASGM1-, preceded by early augmentation of cytotoxic activity of NK cells with a Thy-1-Lyt-1-2-ASGM1+ phenotype. Administration of anti-ASGM1 (10 microliters) in mice resulted in a complete depletion of NK activity and ASGM1+ cells in the spleen even 1 day after injection, but no changes in the proportions of T (Thy-1+) cells and their Lyt-1 and Lyt-2 subsets as revealed by an immunofluorescence analyzer (FACS) and phagocytic cells. When these anti-ASGM1-treated mice were immunized with allogeneic cells, they showed neither augmented NK activity nor generation of alloimmune CTL, and spleen cells isolated from these anti-ASGM1-treated mice produced no CTL response to alloimmunization in vitro. Normal spleen cells treated with the antiserum and complement in vitro also showed a complete NK depletion without any deterioration of T cells and their Lyt-1 and Lyt-2 subsets, and when stimulated with allogeneic cells they generated no CTL. Spleen NK (ASGM1+) cells were purified by Percoll gradient centrifugations followed by complement-dependent killing of T cells with the use of anti-Thy-1 monoclonal antibody, and were further purified by panning methods with anti-ASGM1, giving a preparation consisting of greater than 90% ASGM1+, Ly-5+ cells, and less than 0.5% of Thy-1+, Lyt-1+, and Lyt-2+ cells. These purified ASGM1+ Thy-1- cells alone generated no alloimmune CTL in response to alloantigens, suggesting that ASGM1+ NK cells contained no precursors of alloimmune CTL. When added into NK-depleted spleen cells, they restored the normal alloimmune CTL response of the spleen cells, indicating that ASGM1+ fractions contained cells to provide an accessory function for CTL generation. Lyt-1+ cells purified by panning methods did not restore the CTL response of NK depleted spleen cells. These results indicate that ASGM1+ NK cells, but not Lyt 1+ helper T cells contaminating ASGM1+ fractions at undetectable levels, are responsible for the accessory function. When these purified ASGM1+ Thy-1- cells were stimulated with allogeneic cells, they produced IL 2 and IFN.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2579130 TI - Thymic epithelium. I. Lymphoid-free organ cultures grafted in syngeneic intact mice. AB - Low temperature organ culture of 14 day gestational age mouse thymic lobes leads to the development of a lymphoid-free epithelial matrix. Morphologically, these explants exhibit two distinct epithelial components, which may be indicative of the dual embryologic origin (ectodermal/endodermal) of the thymic epithelium. When such explants are grafted into syngeneic intact recipients, the compound matrix is repopulated by lymphohematopoietic precursors that give rise to an intragraft lymphocyte population. The graft shows additional morphologic development parallel to normal thymus ontogeny. Studies in congenic mice when using the TIa alloantigen as a marker of derivation demonstrate the host origin of these lymphocytes. Cytotoxic assays for the presence of cell surface Thy-1.2, TIa, Lyt-1.2, and Lyt-2.2 reveal that graft lymphocytes express a phenotypic profile and developmental progression that is typical of normal thymocytes. Furthermore, mitogen and mixed leukocyte culture assays show that intragraft lymphopoiesis leads to the generation of a mature population. In addition to the lymphocytes, host-derived Ia+ adherent cells can also be isolated from these thymic epithelial grafts. We conclude that low temperature organ culture-derived thymic epithelium appears to retain those properties of the thymic microenvironment that permit lymphohematopoietic colonization and support thymocyte differentiation. PMID- 2579131 TI - Activation of Lyt-1+ and Lyt-2+ T cell cloned lines: stimulation of proliferation, lymphokine production, and self-destruction. AB - Antigen-induced activation of a chicken gamma-globulin (CGG)-specific Lyt-1+ T cell clone measured both as a function of proliferation and immune interferon (IFN-gamma) production is restricted by a class II determinant of the major histocompatibility complex (MHC) mapped to the I-A subregion, as determined by studies with both recombinant inbred lines and monoclonal antibodies. Activation of Lyt-2+ picryl chloride (PC1)-specific cloned T cell lines by trinitrophenyl (TNP)-coupled spleen cells results in proliferation and the production of at least two lymphokines: lymphotoxin (LT) and IFN-gamma. This antigen-specific activation is restricted to a class I determinant of the MHC complex encoded in the K region. Thus, the common intracellular pathway leading to production of IFN gamma by Lyt-1+ and Lyt-2+ T cells is mediated and restricted through different surface recognition units. The LT that is produced by antigen-specific activation of T cells not only kills fibroblasts, but it inhibits interleukin 2 (IL 2) maintained T cells as well. Activation of T cells by concanavalin A (Con A) results in suicidal inhibition of proliferation and cell death by those clones that make LT, but not by those that produce only IFN-gamma under such induction conditions. These results indicate that it is neither Con A nor IFN-gamma that kills T cells, but LT. These results strongly suggest a self-regulatory role of LT in limiting continuing unrestricted T cell response to antigen activation. PMID- 2579132 TI - Polymorphism and tissue distribution of maternally transmitted antigen defined by cytotoxic T lymphocyte lines. AB - We have developed cytotoxic T lymphocyte (CTL) lines specific for two determinants of the maternally transmitted antigen (Mta) and have used these CTL lines to study the tissue distribution of Mta. In previous reports, we characterized CTL lines specific for the Mta.1 determinant. Here, we describe CTL lines specific for the newly defined Mta.2 determinant. Mta.2-specific CTL lines lysed target cells from F1 mice of an NZB (Mtf beta) mother but did not lyse target cells from reciprocal F1 mice of any Mtf alpha mother. Backcross mice were used as the source of target cells to demonstrate that the Mta.2-specific CTL were H-2 nonrestricted in their recognition. Mta.-1- and Mta.2-specific CTL lines were used to demonstrate Mta expression on lymphoid cells taken from spleen, thymus, lymph nodes, and bone marrow. In addition, Mta was expressed on cultured cell lines of myeloid, epithelial, and mesenchymal origin. Our results suggest that Mta is not a differentiation marker restricted to lymphocyte subpopulations. PMID- 2579133 TI - Lyt-2+ suppressor T cells are resistant to anti-Lyt-2 antibody blocking. AB - Lyt-2 molecules play a role in antigen recognition by cytotoxic T lymphocytes (CTL). In an attempt to determine whether Lyt-2 molecules play a similar role in suppressor T cell (Ts) functions, the effect of anti-Lyt-2 antibodies on Ts generation and effector activity was studied. Allospecific Ts were induced in allogeneic mixed lymphocyte cultures (MLC). Anti-Lyt-2 antibodies added to MLC in the absence of complement abolished CTL generation, but had no effect on concomitant induction of Ts. In a different experimental system, allospecific Ts were induced in cultures treated with pyrilamine, which blocks generation of CTL but allows differentiation of Ts. The addition of anti-Lyt-2 antibodies to pyrilamine-treated MLC resulted in unaffected induction of Ts. It was further demonstrated that the effector activity of Ts was as resistant to anti-Lyt-2 antibodies as their induction, in contrast to the cytolytic activity of CTL, which was inhibited by the same antibodies. Ts in the present experimental system were Lyt-2+ antigen-specific cells. It therefore appears that Lyt-2 molecules, although expressed on both CTL and Ts, are involved in CTL activity, but do not play an essential role in Ts function. PMID- 2579134 TI - B5, a new B cell-restricted activation antigen. AB - The characterization of a new human B cell-restricted activation antigen (B5) is described in this report. With the use of a monoclonal antibody to B5, we show that B5 can be detected on peripheral blood or splenic B cells after 1 day of stimulation with either anti-immunoglobulin, protein A, Epstein Barr virus, or pokeweed mitogen. In contrast, B5 was not expressed on resting B, T, or myeloid cells. More important, B5 could not be detected on activated T cells or monocytes. The B5 antigen was expressed on some lymphoblastoid B cell lines and B cell neoplasms but was not expressed on leukemias or lymphomas of T or myeloid origin. The B5 antigen is distinct from previously reported B cell activation antigens by its m.w. and pattern of cellular expression. These studies suggest that B5 is a novel B cell-restricted activation antigen, which may be useful to study the events of early human B cell activation. PMID- 2579135 TI - Delayed maturation of the antibody response to type 2 thymus-independent antigens in a partially inbred strain of chicken. AB - The ontogeny of antibody responses to trinitrophenylated (TNP) thymus-independent (TI) antigens was compared in two partially inbred strains of chicken: the SC strain (B2/B2 genotype) and the FP strain (B15/B22 genotype). In the SC chicken, maturation of both the splenic anti-TNP plaque-forming cell (PFC) response and the 19S hemagglutinating antibody response to TI type 2 (TI-2) antigens, TNP Ficoll and TNP-dextran, were delayed to a significantly later time in ontogeny (20 wk of age) than in the FP chickens (9 wk of age). Four- to 6-wk-old SC chickens were virtually immunologically unresponsive to stimulation with TI-2 antigens. The TI-1 antigen TNP-Brucella abortus was equally immunogenic in both FP and SC chickens of different age groups tested. Kinetic studies of the primary PFC response to TNP-Ficoll in immunologically mature chickens of the SC and FP strains demonstrated a peak PFC response 4 days after antigen injection, followed by a rapid decline in numbers of splenic PFC/spleen on day 6. The results of these studies are discussed in relation to earlier observations that suggested there may be a delay or a defect in the ontogeny of the thymus in the SC chicken. PMID- 2579136 TI - The function of antigen-presenting cells in mice with severe combined immunodeficiency. AB - We have examined the antigen-presenting function of spleen cells in the C.B-17 scid mouse, a mutation that severely impairs the development of T and B lymphocytes. We show that antigen-presenting cells (APC) of SCID mice function normally in antigen-specific proliferative responses of primed T cells and in the antigen-specific activation of IL 2-producing T cell hybridomas. In both quantitative and qualitative terms, APC of SCID mice are equivalent to those of normal mice. These results indicate that the development and differentiation of APC function in vivo is independent of signals from mature, functional T or B lymphocytes. PMID- 2579137 TI - The role of T8 in the cytotoxic activity of cloned cytotoxic T lymphocyte lines specific for class II and class I major histocompatibility complex antigens. AB - It is reported here that most cytotoxic T lymphocytes (CTL), which recognize class I major histocompatibility complex (MHC) loci, express the T cell differentiation antigen T8. However, a minority of T8+ CTL clones was found to recognize class II MHC antigens. To test the hypothesis that T8 is involved only in T cell recognition of class I MHC antigens, we studied the role of T8 in the cytotoxic activity of class II MHC-specific CTL. Monoclonal antibodies specific for T8 blocked the activity of most class I MHC-specific CTL clones but did not affect the activity of class II MHC-specific CTL clones. Moreover, a mild trypsin treatment of the clones, which removed and T8 determinant, affected the activity of class I MHC but not that of class II MHC-specific CTL clones. These findings indicate that the class II-specific MHC CTL clones described here did not require T8 for their cytolytic activity. The activity of one T8+ class I MHC-specific (HLA-B27) CTL clone (HG-61) against the B cell line JY, which was used to raise this CTL clone, was not blocked by trypsin treatment of this clone. However, the activity of CTL clone HG-61 against target cells different from JY but carrying the appropriate HLA specificity was blocked by anti-T8 antibodies and trypsin treatment. The implications of these findings for the hypothesis that T8 is involved only in the activity of CTL with a relatively low avidity for class I MHC antigens are discussed. PMID- 2579138 TI - In vitro migration of human large granular lymphocytes. AB - Large granular lymphocyte (LGL)-enriched peripheral blood mononuclear cells were prepared on discontinuous gradients of Percoll. Migration into nitrocellulose filters was studied in a 2-hr assay with the use of modified Boyden chambers. LGL migrated into filters in response to casein or C5a. Migration depended on the presence of a concentration gradient of chemoattractant between the lower and upper compartment of the chambers. Percoll-purified high density small lymphocytes had little or no migratory capacity under these conditions, requiring a longer incubation time (4 hr) for consistent migration. Migratory capacity in response to stimuli correlated with the frequency of LGL in the various fractions of Percoll gradients. Fractionation of LGL-enriched Percoll preparations with monoclonal antibodies and immunoadsorbent columns or a cell sorter revealed that cells with migratory capacity in response to stimuli were B73.1+ and OKT3-, thus confirming that migrating cells were LGL. LGL preincubated with interferon (IFN) showed enhanced spontaneous motility but no increased responsiveness to chemoattractants. IFN did not modify the migratory capacity of small lymphocytes. The prompt migration of LGL in response to stimuli is consistent with the hypothesis that these cells may serve as one of the first easily mobilizable lines of resistance against infectious agents and tumors. The migration assay described here may offer a better insight into the functions and regulation of LGL. PMID- 2579139 TI - Characterization of T cell lines and clones from SJL/J and (BALB/c x SJL/J)F1 mice specific for myelin basic protein. AB - Lines of thymus-derived lymphocytes reactive against bovine myelin basic protein (BP) were established in vitro from SJL/J mice. These lines are stable in long term culture and mediate inflammatory central nervous system (CNS) lesions and a low incidence of clinical experimental allergic encephalomyelitis (EAE) when injected into recipient SJL/J mice. The line cells proliferate in response to BP of bovine, rat, or mouse origin. Clones were derived from these lines, and the characteristics of these clones were analyzed. The clones express Thy-1, Ly-1, and L3T4 antigens and are negative for Ly-T2. The clones all proliferate in response to bovine BP, with different clones showing varying degrees of cross reactivity between bovine, rat, and mouse BP. The proliferative response is MHC restricted; antigen-presenting cells from I-As strains are required. Compatible with their phenotype as helper cells, some of the clones will provide help to primed B cells stimulating antibody production in an in vitro assay. When injected into recipients pretreated with pertussis and irradiation, clones that showed proliferation to mouse BP induced the development of inflammatory lesions in the CNS, with mortality of 28% of the recipients. T cell lines were also established in (BALB/c x SJL/J)F1 mice. In contrast to the homozygous SJL/J lines, these lines were highly encephalitogenic, inducing a high incidence of clinical and histologic EAE when injected in vivo. PMID- 2579140 TI - Major histocompatibility complex-linked control of the murine immune response to myelin basic protein. AB - Recent experiments have shown that different regions of myelin basic protein (MBP) are encephalitogenic for different inbred strains of mice. It was therefore of interest to determine whether the immune response to MBP was MHC associated, and if so, what subregion controlled this response. Because PL/J and A/J mice were good responders to mouse MBP and C57Bl/10SN were not, B10.PL(73NS) and B10.A mice were immunized with mouse MBP under conditions designed to induce EAE. These strains were found to be highly susceptible. Intra-H-2 recombinant mice were then assessed for susceptibility. B10.A(4R) and B10.MBR were susceptible, whereas B10.A(5R) were resistant. Thus, EAE induced by purified MBP is under the control of the MHC, and the response maps to the I-A subregion. Production of IL 2 in vitro by T cells from MBP-primed mice in the presence of antigen and adherent cells was blocked by monoclonal antibody to the I-A, but not the I-E, subregion. When the specificity of the encephalitogenic response was tested, peptide 1-37 was active in B10.PL(73NS) and B10.A mice, whereas peptide 89-169 was active in A.SW, SWR, and B10.T(6R) strains. Serum from mice immunized with MBP peptides was assayed for antibody content. PL, B10.PL, and B10.A mice made a good antibody response to peptides 1-37 and 43-88 but were nonresponsive to peptide 89-169. SJL, A.SW, SWR, and B10.T(6R) mice responded well to peptide 89-169 but were poorly responsive to peptides 1-37 and 43-88. PMID- 2579141 TI - The immunopathology of experimental allergic encephalomyelitis (EAE). III. Differential in situ expression of strain 13 Ia on endothelial and inflammatory cells of (strain 2 x strain 13)F1 guinea pigs with EAE. AB - This study was undertaken to determine if there is differential expression of the relevant strain-specific Ia antigen on endothelial and parenchymal inflammatory cells in the central nervous systems (CNS) of guinea pigs (GP) with acute experimental allergic encephalomyelitis (EAE). Adult inbred GP were sensitized with GP spinal cord homogenate and complete Freund's adjuvant. Strain 13 GP and (2 x 13)F1 hybrids developed clinical disease within 2 to 3 wk after sensitization, whereas strain 2 GP did not, although all sensitized GP had CNS mononuclear inflammatory infiltrates. By using monoclonal antibodies to strain specific and framework Ia epitopes with an immunoperoxidase technique, the distribution and amount of the strain 2 and strain 13 Ia were analyzed. Equivalent strain 2 and strain 13 Ia expression was found in normal tissues from F1 animals. Strain 2 and strain 13 GP sensitized for EAE had increased strain specific Ia staining of CNS vessels and inflammatory cells over controls. However, F1 GP with EAE had markedly increased strain 13, but not strain 2, Ia on CNS parenchymal vessels and mononuclear inflammatory cells (p less than 0.001, for both). These results suggest for the first time that specific major histocompatibility complex gene products are selectively expressed on endothelial and inflammatory cells in situ in immune reactions in the target organ of individuals of heterogeneous immunogenetic composition. PMID- 2579142 TI - Murine interstitial nephritis. III. The selection of phenotypic (Lyt and L3T4) and idiotypic (RE-Id) T cell preferences by genes in Igh-1 and H-2K characterizes the cell-mediated potential for disease expression: susceptible mice provide a unique effector T cell repertoire in response to tubular antigen. AB - The effector T cell repertoire in experimental interstitial nephritis was examined in a variety of susceptible and nonsusceptible mice. We observed that L3T4+ effector T cells in disease-susceptible mice disappear soon after immunization in preference to the emergence of Lyt-2+ effector cells. These latter cells respond with delayed-type hypersensitivity to tubular antigen in the context of H-2K. Such cells also express idiotypes (RE-Id) shared with kidney bound alpha TBM-Ab that are regulated by an interactional effect of genes in Igh 1 and H-2K. These Lyt-2+ effector cells can be removed from renal infiltrates, and the transfer of similar cells under the renal capsule of naive mice results, within 5 days, in local interstitial nephritis. Nonsusceptible mice, however, not having these immune response genes, produce either L3T4+, Lyt-1+, RE-Id- effector T cells, which only respond to tubular antigen in the context of I-A, or Lyt-2+, RE-Id- T cells, which may lack very fine specificity. These findings suggest that susceptible mice carry a unique set of immune response genes that promote a T cell selection process that operates after induction, during the differentiation and development of disease-producing effector T cells. PMID- 2579144 TI - An analysis of the structure of the antigen receptor on a pigeon cytochrome c specific T cell hybrid. AB - The monoclonal antibody A2B4-2 has been shown to bind to the antigen receptor on the cloned pigeon cytochrome c-specific T cell hybrid, 2B4. Initial immunoprecipitation and SDS-PAGE analysis with this clonotypic antibody demonstrated that the antigen receptor on this cell had a m.w. of 85,000 to 90,000. Under reducing conditions, the receptor protein appeared as two bands of 45,000 to 50,000 and 40,000 to 44,000 on an SDS-PAGE gel. In this paper the antigen receptor on this T cell hybrid is further characterized. The molecule is shown to be a heterodimer that exists in two different forms on the cell surface. Receptor molecules with an apparent m.w. of 84,000 and 86,000 were isolated by immunoprecipitation and separation on polyacrylamide gradient gels. After reduction, the individual alpha- and beta-chains were separated by isoelectric focusing. In both forms of the receptor, the acidic alpha-chain had an apparent m.w. of 42,000 to 44,000. This alpha-chain associated with one of two forms of beta-chain. One beta-chain had a m.w. of 42,000 to 44,000, with a pI range of 7.5 to 7.9, and the alternate form of the beta-chain, beta', had a m.w. of 46,000 to 48,000 and a more acidic pI range of 6.5 to 7.5. The results of this investigation indicate that under reducing conditions on SDS-PAGE gels, the original upper 45,000 to 50,000 m.w. band represented beta'-chains alone, whereas the lower 40,000 to 44,000 m.w. band represented a mixture of alpha- and beta chains. Additional data are presented to indicate that this heterodimeric protein has intrachain as well as interchain disulfide bonds. This conclusion was reached from the characteristic pattern of protein migration on SDS-PAGE gels in the presence of a reducing agent concentration gradient. Thus, both chains of the antigen receptor must have intrachain disulfide bonds and may have similar domain structures. PMID- 2579143 TI - Interleukin 2-mediated induction of lytic activity in a cloned murine CTL line. AB - We have analyzed the ability of interleukin 2 (IL 2) to induce lytic activity within a cloned murine H-2Dd-specific CTL line. Weakly lytic CTL harvested 6 to 7 days after previous stimulation with irradiated DBA/2J spleen cells and conditioned medium from secondary MLC (MLC SN) could be reactivated to high antigen-specific lytic activity with highly purified gibbon IL 2 or E. coli produced human recombinant DNA IL 2. Dose-response curves with IL 2 and MLC SN suggest that IL 2 may be the principal detectable activity in MLC SN that is active on these CTL. Doses of IL 2 or MLC SN that were saturating for the induction of lytic activity were suboptimal for the expression of DNA synthesis measured by 3HTdR incorporation. This is consistent with a mechanism in which different threshold IL 2 concentrations are required to induce these two biologic responses. Finally, we show that IFN-gamma has little effect on the expression of lytic activity either alone or in combination with IL 2 in this bioassay. PMID- 2579145 TI - Antigen-specific anti-phosphocholine antibodies: binding site studies. AB - The present investigation extends our initial evaluation of the evolution of antigen selection mechanisms for antibodies of a "single" specificity. The binding sites of 11 mouse anti-PC antibodies produced in response to the bacterium P. morganii or the nematode A. suum were characterized for both hapten and hapten plus carrier specificity. All of the anti-P. morganii HP belonged to the M603 anti-PC antibody family, whereas all the A. suum HP belonged to the M511 family. Of the eight anti-P. morganii HP, six exhibited a fine specificity profile for PC and choline analogues only slightly different from M603 Id+ HP induced by S. pneumoniae and PC-protein. These six and a seventh HP, whose hapten binding profile was unique, were also unusual in showing strong reactivity for a soluble PC containing extract from P. morganii. All three anti-A. suum-specific HP studied in detail had hapten-binding profiles remarkably similar to each other, a finding that is in contrast to M511 Id+ HP to S. pneumoniae and PC protein. All three HP also showed evidence for preferential binding activity for A. suum, although this was not as dramatic as that seen with the anti-P. morganii HP. These data support our hypothesis that antigen selection of anti-PC antibodies occurs not so much for PC itself as it does for the carrier (microbial) determinants to which PC is attached. PMID- 2579146 TI - A beta-glucan inhibitable receptor on human monocytes: its identity with the phagocytic receptor for particulate activators of the alternative complement pathway. AB - The ligand specificity of the human monocyte receptor that mediates phagocytosis of particulate activators of the human alternative complement pathway was defined by inhibiting the phagocytic response with glycans known to be present in zymosan. When monocytes in monolayers were preincubated with 100 micrograms/ml of beta-glucan and then incubated with 1.25 to 2.5 X 10(6) zymosan particles, the percentage of cells that exhibited phagocytosis was inhibited in a time-dependent manner; maximal inhibition occurred within 20 min of preincubation. beta-Glucan inhibited monocyte phagocytosis of zymosan and rabbit erythrocytes (Er) in a similar dose-dependent fashion and at 100 micrograms/ml reduced monocyte ingestion of 5 X 10(6)/ml zymosan and 2 X 10(8)/ml Er by 63 +/- 8% and 68 +/- 16% (mean +/- SD, n = 3), respectively. The other glycan constituent of zymosan, mannan, was less than 1% as active, and 10 mg/ml of mannan reduced the number of monocytes ingesting zymosan and Er by 56 +/- 12% and 26 +/- 11%, respectively. At concentrations as high as 500 micrograms/ml, beta-glucan had no effect on monocyte Fc, C3b, or fibronectin receptor-mediated functions. Enzymatic hydrolysis of beta-glucan and alpha-mannan with beta-glucosidase or beta glucanase before their incubation with monocytes abrogated their inhibitory capacity, whereas hydrolysis with alpha-mannosidase or alpha-glucosidase did not. Neither of the two alpha-glucans tested (dextran T-70 and nigeran) affected monocyte ingestion of zymosan particles or sheep erythrocytes (Es) sensitized with rabbit 7S anti-Es (EsIgG) at concentrations as high as 2 mg/ml. In contrast, a number of beta-glucans were active against zymosan but not EsIgG ingestion with a 75% reduction in the number of monocytes ingesting zymosan occurring with 100 micrograms/ml laminarin, 500 micrograms/ml soluble pachyman, and 900 micrograms/ml of soluble pustulan. The galactan, agarose, either in suspensions at 2 mg/ml or in a soluble portion at 600 micrograms/ml failed to affect monocyte ingestion of zymosan particles or Er. Thus, the monocyte receptor for particulate activators that is specifically inhibited by beta-glucan at a rate compatible with a phagocytic process and that recognizes beta-glucans but not alpha-glucans, mannan, or galactan is a beta-glucan receptor. PMID- 2579147 TI - The relationship between channel size and the number of C9 molecules in the C5b-9 complex. AB - We have recently shown by dose-response analyses with resealed erythrocyte ghosts that the channel formed by complement is a monomer of C5b-9 of the composition C5b61C71C81C9n, in which n = 1 for channels permitting passage of sucrose (0.9 nm molecular diameter) and n = 2 for channels allowing transit of inulin (3 nm molecular diameter) (1). We have now continued these experiments and expanded them by including ribonuclease A (molecular diameter, 3.8 nm) as a marker to assess whether additional C9 molecules enlarge the functional C5b-9 channel. Our results show that formation of C5b-9 channels displays one-hit characteristics with respect to C5b6 when tested by transmembrane passage of inulin or ribonuclease A. By contrast, analysis of dose-response curves of C9 indicate that n = 2-3 for channels allowing transit of inulin and n = 4 for channels allowing transit of ribonuclease A. We have also performed sieving experiments with ghosts carrying C5b-7 and containing two small markers, inositol and sucrose. Dose response curves for C8 were performed in the presence of excess C9 to ensure conversion of all C5b-8 to C5b-9 channels. The results indicate that small channels (approximately 0.8 nm effective diameter) are not formed at high C9 multiplicity, thus confirming the results obtained with the larger markers, i.e., increase of C9 input leads to formation of larger channels. PMID- 2579148 TI - Determinant specificities of the groups B and C polysaccharides of Neisseria meningitidis. AB - A meningococcal group B-specific horse antiserum contains at least two distinct populations of antibodies with specificities for determinants on the group B capsular polysaccharide antigen. These two populations were differentiated on the basis of the ability of only one of them to be absorbed from the antiserum by the structurally related colominic acid. The nature of the colominic acid-specific determinant was elucidated by a radioimmunoassay inhibition technique with the use of a series of linear alpha-(2----8)-linked oligomers of sialic acid as inhibitors. Colominic acid was labeled by prior removal of its N-acetyl groups, followed by their replacement with the use of [3H]acetic anhydride. The conformational nature of the determinant was proposed because of the unusually large size (10 sialic acid residues) of the oligomer required to function as an efficient inhibitor. The structure of the determinant responsible for the second population of group B-specific antibodies has not been determined, but it is obviously based on an as yet undefined conformational or structural feature peculiar to the group B meningococcal polysaccharide. In contrast to the colominic acid-specific group B determinant, the determinant responsible for the group C polysaccharide-specific rabbit antibodies proved to be more conventional. Inhibitory properties of the alpha-(2----9)-linked oligomers maximized with those containing four or five sialic acid residues, which is consistent with the approximate estimated maximal size of an antibody site. PMID- 2579149 TI - Human cytotoxic T cell clones directed against herpes simplex virus-infected cells. III. Analysis of viral glycoproteins recognized by CTL clones by using recombinant herpes simplex viruses. AB - Human cytotoxic T cell (CTL) clones specific for herpes simplex virus (HSV) type 1- and type 2-infected cells were generated and were analyzed with regard to the viral glycoproteins they recognize on autologous HSV-infected cells. By use of target cells infected with wild-type HSV strains, a gC deletion mutant of HSV-1, and HSV-1 X HSV-2 intertypic recombinants, some HSV-1-specific CTL clones were found to be directed against L region-encoded gA/B-1, and others against S region encoded glycoproteins (gD-1 or gE-1). Some HSV-2-specific clones were found to be directed against L region-encoded gC-2, whereas others were directed against S region-encoded glycoproteins (gD-2, gE-2, or gG). These findings provide direct evidence that several HSV glycoproteins that are expressed on the surface of HSV infected cells serve as recognition structures for human HSV-specific CTL. PMID- 2579150 TI - Frequency of herpes simplex virus-specific helper T lymphocyte precursors in the lymph node cells of infected mice. AB - We have established a limited dilution assay to estimate the frequency of herpes simplex virus type 1 (HSV)-specific, interleukin 2 (IL 2)-producing helper T lymphocyte precursors (HTL-P). The estimated frequency of such cells in suspensions of local lymph node (LN) cells 5 days after in vivo virus infection was 1:2470 to 1:5800. Frequencies of HTL-P in cells from uninfected mice were below levels of detection of our system and were judged to be below 1:100,000. Removal of Lyt-2+ cells from responder LN cells before culture increases HTL-P frequency twofold to threefold, indicating the likely operation of some form of suppression in unseparated cultures. The demonstration of HSV-specific HTL-P required that cells from virus-primed mice be reexposed in vitro to viral antigen. In addition, clones expanded during a 9-day culture period failed to generate IL 2 unless reexposed to specific viral antigen or cross-reactivate HSV 2. Thus, HSV-specific HTL-P were strictly antigen dependent. No evidence was obtained for antigen-independent subpopulations of HTL-P as occurs with viral specific cytotoxic T lymphocyte precursors. The clonal progeny of HTL-P were of the Thy-1+ Lyt+2- phenotype. Priming in vivo for the subsequent in vitro detection of HTL-P required that mice be exposed to infectious virus. Thus neither UV-inactivated nor heat-inactivated nor extracted viral glycoproteins could prime for HTL-P detection. The relevance of these findings for the future use of subunit vaccines against HSV is briefly discussed. PMID- 2579151 TI - In vitro antigen-specific antibody response to the species-specific surface protein antigens of typhus group rickettsiae by human peripheral blood mononuclear cells: generation of an antigen-dependent suppressor T cell. AB - We defined conditions suitable for in vitro synthesis of rickettsia-specific antibody by human PBMC cultured with the SPA of Rickettsia typhi or R. prowazekii and without addition of mitogens or polyclonal stimulators. Antibody synthesis, as measured by an enzyme-linked immunosorbent assay, was cycloheximide inhibitable and antigen-specific. PBMC from individuals with prior rickettsial infection made antibody, whereas PBMC from those receiving vaccine or with undetectable levels of serum anti-SPA antibody did not. Antibody production was T helper cell-dependent because isolated B cells did not generate antigen-specific antibody in the absence of autologous T cells. Furthermore, prior exposure of T cells to high concentrations of SPA led to the generation of an antigen-dependent population of cells capable of suppressing the anti-SPA response when co-cultured with autologous PBMC and optimal SPA concentrations. This system should serve as an effective tool for analyzing the cellular interactions involved in the in vitro regulation of antigen-specific antibody synthesis by human PBMC. PMID- 2579152 TI - Lysis of human cytomegalovirus infected fibroblasts by natural killer cells: demonstration of an interferon-independent component requiring expression of early viral proteins and characterization of effector cells. AB - We investigated the susceptibility of cells infected with human cytomegalovirus (HCMV) to lysis by human natural killer (NK) cells, examining in particular its relationship to sequential viral protein expression, interferon (IFN), and the nature of the effector cells. HCMV-infected fibroblasts were lysed by peripheral blood mononuclear cells from normal seronegative individuals. The effector cells were large granular lymphocytes of Leu-7+, Leu-11+, and to a lesser extent Leu-7- phenotype. Depletion studies suggested they were the same population of NK cells that lyse uninfected fibroblasts, but a subset of NK cells that lyse K562 cells. HCMV-infected cells treated with phosphonoformate and cells infected for 16 hr that only express the nonstructural HCMV immediate early and early proteins and not the late (structural) proteins were susceptible to lysis by IFN-pretreated effector cells, whereas cells expressing immediate early antigens alone were not. This enhanced susceptibility to lysis was associated with increased effector:target binding in target cell binding assays, and was competitively inhibited by uninfected fibroblasts in cold target competition assays. It was independent of IFN release from the infected target cells or effector cells. These results suggest that the increased susceptibility to lysis by NK cells produced by a human herpes virus HCMV i) is manifest when early viral proteins are expressed, ii) is related to enhanced expression of a target structure likely to be present on uninfected fibroblasts, and iii) has a major component that is independent of IFN. PMID- 2579154 TI - Prominence of IgG4 in the IgG antibody response to human filariasis. AB - The four subclasses of IgG are distinct in structure, function, and degree of participation in the response to complex antigens. Because these differences could have important pathogenetic significance, we analyzed total and filaria antigen-specific IgG of each subclass in 31 patients with different clinical manifestations of Bancroftian filariasis. Subclass-specific, affinity-purified polyclonal antibodies were prepared from antisera raised in sheep immunized with purified myeloma IgG subclass proteins. These were radiolabeled (125I) and used to detect IgG1, IgG2, IgG3, and IgG4 in solid phase radioimmunoassays (SPRIA). The antigen-specific SPRIA was used with Brugia malayi adult antigen (BmA) bound to Sepharose 4B, whereas measurement of total IgG subclass levels in each serum was with goat anti-human IgG bound to the solid matrix. Quantification of total subclass levels was by reference to the WHO 67/97 standard, and of specific subclass antibody by development of standards from high titered sera. Although there were modest increases of total IgG1 and IgG2 in patients with filariasis compared with normals, the most striking finding was the extreme elevation of both total, and particularly, filaria antigen-specific IgG4. These elevations were seen for essentially all patients, but the relative proportion of the total IgG antibody response accounted for by IgG4 antibody was particularly marked (up to 95%) in patients with either microfilaremia or the tropical pulmonary eosinophilia syndrome. The meaning of this special prominence of the IgG4 antibody response to filarial infection is not yet clear, but the question of whether these antibodies play a role in immediate hypersensitivity reactions as either reagins or blocking antibodies is being investigated for its potential pathogenetic significance. PMID- 2579153 TI - Cell receptors for the mammalian reovirus. IV. Reovirus-specific cytolytic T cell lines that have idiotypic receptors recognize anti-idiotypic B cell hybridomas. AB - Cytotoxic T lymphocyte (Tc) cell lines specific for reovirus type 3 lysed an uninfected B cell hybridoma line, 87.92.6, that expresses and secretes an anti idiotypic antibody that reacts with an anti-viral hemagglutinin monoclonal antibody, 9BG5. Monoclonal anti-idiotype 87.92.6 was shown by fluorescence analysis to specifically bind to reovirus Tc and to block reovirus-specific Tc from killing reovirus-infected target cells or the 87.92.6 hybridoma. An anti-LFA 1 monoclonal antibody, M17, interfered with Tc-mediated lysis of reovirus infected targets and the 87.92.6 cells, indicating the similarity of cellular interactions mediated by LFA-1 structures when Tc bind to virally infected targets or 87.92.6 targets. Together with studies in which anti-H2 or monoclonal idiotypic antibodies were found to interfere with reovirus-specific Tc recognition of virally infected or 87.92.6 targets, these experiments indicate that some reovirus-specific Tc have conformations in their receptor that can be recognized by anti-idiotype. PMID- 2579155 TI - Genetics of resistance to the African trypanosomes. V. Qualitative and quantitative differences in interferon production among susceptible and resistant mouse strains. AB - The induction of interferon (IFN) was examined in different inbred mouse strains infected with Trypanosoma brucei rhodesiense. Relatively susceptible C3HeB/FeJ mice that do not exhibit variant-specific immunity or control parasitemia did not exhibit detectable IFN throughout the infection. Relatively resistant B10.BR mice that exhibit variant-specific immunity and control the first peak of parasitemia exhibited detectable IFN at two intervals. The appearance of IFN in B10.BR serum first coincided with the onset of the parasitemia 4 days after infection and then disappeared; this IFN peak was predominantly IFN-alpha/beta. The second time of appearance coincided with high titers of antibody and remission of the parasitemia. This IFN was predominantly IFN-gamma. Intermediately susceptible CBA/J mice also exhibited two detectable peaks of IFN; the first IFN-alpha/beta peak coincided with the onset of the parasitemia as in B10.BR mice. The second peak of IFN in the serum of CBA mice, however, was delayed in appearance and lower in concentration compared with B10.BR mice. This peak was characterized as being predominantly IFN alpha/beta. BALB/c mice (also intermediately susceptible) did not exhibit a first peak of IFN-alpha/beta production, but the second peak of IFN-alpha/beta production was similar to that seen in CBA mice. In contrast to infected mice, IFN was induced in both susceptible (C3H) and resistant (B10.BR) mice after immunization with glutaraldehyde-fixed trypanosomes or after chemotherapy of infection. We conclude that both the levels of IFN as well as the type of IFN induced during infection with T. b. rhodesiense depend upon the genetic background of the mouse strain infected. The induction of IFN-gamma in mice of the C57BL background may be linked functionally to more effective parasite control and to the presence of an effective immune response to T. b. rhodesiense. PMID- 2579156 TI - Isolation and characterization of a tumor-specific T suppressor factor from a T cell hybridoma. AB - In our laboratory we have described a monoclonal antibody, B16G, which has been shown to bind to suppressive T cell factors (TsF) in DBA/2 mice. Therefore, B16G was used as a probe to identify T cell hybridomas secreting putative TsF. Hybridomas were obtained by the fusion of DBA/2 thymocytes stimulated in vivo by P815 tumor membrane extracts with the thymoma BW5147. One such hybridoma, A10, was selected and used for additional studies. From both the supernatants and ascites fluid of this hybrid a factor could be obtained that could specifically bind to both B16G and P815 antigen immunoadsorbent columns, and that scored positively with B16G in an ELISA after elution. Such reactivity could not be obtained from A10 supernatants or ascites absorbed over irrelevant columns, nor was it obtained from supernatants or ascites from other T cell hybrids that had scored B16G nonreactive in the original screening. In vivo studies indicated that affinity-purified A10 material injected into DBA/2J mice enhanced significantly the growth of P815 tumor cells, but not the growth of other DBA/2 syngeneic tumor lines such as L1210 or M-I. Additionally, this material did not inhibit the in vitro mixed leukocyte reaction (MLR) between DBA/2 splenocytes and allogeneic B10.BR target cells (unlike B16G purified material from whole DBA/2 spleens, which has been demonstrated to be suppressive in this type of MLR). Biochemical analysis of this tumor-specific TsF from A10 was undertaken; the native m.w. was found to be in the region of 80,000 and 90,000. Under reducing conditions, affinity-purified A10 TsF was found to resolve in SDS-PAGE as what appeared to be a heterodimer of 45,000 and 43,000. In most preparations, an associated molecule resolving at about 25,000 was observed. The implications of these observations are discussed. PMID- 2579157 TI - Changes in number and density of large granular lymphocytes upon in vivo augmentation of mouse natural killer activity. AB - NK activity of mice as well as humans and rats has been clearly associated with large granular lymphocytes (LGL). To better understand the effects of interferon (IFN) and IFN inducers on natural killer (NK) cells, we have compared the LGL in the spleens of normal and boosted mice. Cells were fractionated by centrifugation on discontinuous Percoll density gradients, and each fraction was tested for NK activity against YAC-1 targets and for the presence of LGL. In vivo treatment with C. parvum (0.7 mg/mouse, i.p., day-3), MVE-2 (25 mg/kg, i.p., day-3), poly I:C (4 mg/kg, i.p., day-3), or IFN (10(5) U/mouse, i.p., day-1) resulted in a marked augmentation and a change of distribution of cytotoxic activity. Most of the NK activity of boosted spleen cells was associated with lower density fractions 1 and 2, whereas active normal spleen cells had somewhat higher density (fractions 2 and 3). In parallel to their increased reactivity, the boosted spleens had a marked increase in the percentage of LGL, particularly in fractions 1 and 2. The augmented activity appeared to be mediated by the LGL, because treatment with anti-asialo GM1 or anti-Thy-1.2 plus complement reduced NK as well as the number of LGL. These results indicate that IFN-mediated boosting of NK activity in the spleen is due to an increase in the lower density LGL, as well as to an increase in the function of preexisting NK cells. PMID- 2579158 TI - Immunoenzymatic analysis by monoclonal antibodies of bacterial lipopolysaccharides after transfer to nitrocellulose. AB - A rapid, sensitive immunoenzymatic technique for the analysis of lipopolysaccharide (LPS) from gram-negative bacteria using monoclonal antibodies is described. After separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the LPS was either stained with silver or electrophoretically transferred to nitrocellulose. After reaction with anti-LPS monoclonal antibodies, the transferred antigens were visualized by reaction with alkaline phosphatase-labelled anti-mouse antibodies and a substrate containing naphthol phosphoric acid and Fast Red. PMID- 2579159 TI - A simple bioassay for monocyte-derived hepatocyte stimulating factor: increased synthesis of alpha 2-macroglobulin and reduced synthesis of albumin by cultured rat hepatocytes. AB - Cytokines released from monocytes upon stimulation by lipopolysaccharide cause a number of cells to undergo proliferative and synthetic changes. At least one of these cytokines affects hepatocytes in vivo causing increased synthesis of a series of acute-phase proteins. We have established an in vitro micro-assay for hepatocyte stimulating factor (HSF) using primary cultures of normal rat hepatocytes. Measurement of increased synthesis of alpha 2-macroglobulin and decreased synthesis of albumin caused by exogenously added factor constitute a sensitive parameter for quantifying HSF. For comparing various cytokines preparations, we have defined a unit of HSF activity in terms of a stimulation index. We have used this assay to follow some preliminary attempts to isolate the factors responsible for stimulation of synthesis of acute-phase reactant by the liver. PMID- 2579160 TI - Cloning of mitogen- and antigen-reactive B lymphocytes on filter paper discs. I. A description of the technique and of methods for the analysis of colonies. AB - A novel technique for establishing short term clones of antigen- or mitogen activated splenic B lymphocytes is described. Spleen cells are plated onto the surface of filter paper discs and subsequently stimulated by antigen or mitogen in situ; activated B cells proliferate and differentiate into pure colonies of cells analogous to bacterial colonies growing on agar. These colonies of lymphocytes may be characterized in a series of replica hemolytic-plaque, autoradiographic, or immunoenzyme assays making possible a full characterization of the frequency of secreted idiotopes and paratopes and of the cells that produce them. Colony induction by either antigen or mitogen occurs under identical conditions, thus a rigorous comparison between the mitogen-selected and antigen-selected antibody repertoires may be made. PMID- 2579161 TI - Large-scale purification of Epstein-Barr virus membrane antigen gp340 with a monoclonal antibody immunoabsorbent. AB - A purification method has been elaborated to isolate Epstein-Barr (EB) virus membrane antigen, gp340, in milligram amounts. The gp340 was prepared from detergent extracts of B95-8 cells by affinity chromatography with a monoclonal antibody immunoabsorbent. Bound material was eluted and the eluate, consisting of 50% gp340, was then fractionated by gel filtration. The final gp340 product was antigenically active and 95% pure. The purification method was found to be rapid and reproducible with no loss of the ability of the immunoabsorbent to retain gp340 after repeated elution. The procedure provides suitable material to permit the detailed structural analysis of gp340 necessary for both vaccine design and for the investigation of the role of gp340 in immunity to EB virus infection. PMID- 2579162 TI - The selection of antibodies with defined desorption properties from precipitated immune complexes for use in immunoadsorption procedures. AB - A general method for preparing immunosorbents with preselected antibody avidity is described. The method, which is a modification of a method described previously, also includes immunospecific purification of the ligand prior to coupling on the gel matrix. Polyclonal anti-alpha-1-fetoprotein antibodies in precipitated immune complexes were separated according to their avidity (low, intermediate and high) by dissociation with agents of increasing efficiency. After solid-phase coupling the antigen binding activity of the separated antibody preparations was examined according to recovery, capacity and binding strength. Antibodies of intermediate avidity derived from the immune complexes demonstrated optimal properties for preparative affinity chromatography. PMID- 2579163 TI - The permeability of skin and oral mucosa to water and horseradish peroxidase as related to the thickness of the permeability barrier. AB - The permeability of porcine skin and keratinized and nonkeratinized oral mucosa to tritium-labeled water and horseradish peroxidase (HRPO) was determined using perfusion chambers. Small blocks from each tissue were also incubated with HRPO and the extent of penetration visualized microscopically; this enabled measurements to be made of the thickness of the permeability barrier to this water-soluble tracer. Results obtained after inverting the oral mucosa in the chambers or adding metabolic inhibitors indicated that both compounds diffuse across the tissue. The permeability constants derived directly in the study showed that skin was less permeable than oral mucosa and that the floor of the mouth was significantly more permeable than all other regions. When these constants were normalized in terms of a standard permeability barrier thickness and the different tissues compared, the values obtained for skin were again less than those of the oral regions but, of these, the buccal mucosa was significantly higher. The difference in permeability between epidermis and keratinized oral epithelium may be due to differences in the volume density of membrane-coating granules known to exist between the tissues; differences between the oral mucosal regions may reflect differences in the nature of the intercellular barrier material. PMID- 2579165 TI - Increased calmodulin levels in psoriasis and low Ca++ regulated mouse epidermal keratinocyte cultures. AB - Calcium has been shown to regulate the proliferation of epidermal keratinocytes in vitro. We became interested in the role of the calcium binding protein, calmodulin, in hyperproliferative, low calcium regulated keratinocytes in vitro and in the in vivo hyperproliferative state, psoriasis. Calmodulin levels were measured by radioimmune assay in neonatal mouse keratinocytes grown in 0.02 mM calcium (hyperproliferative) and 1.2 mM calcium (normal) media, and in cells that had been grown in low calcium medium and then switched to normal calcium. On a whole culture basis the normal cells had more calmodulin than the low calcium cells. However, when low calcium monolayers were compared to the normal basal monolayer, the low calcium hyperproliferative cells had more calmodulin. Cells that were switched from 0.02 mM calcium to 1.2 mM calcium showed increasing calmodulin levels over time. Psoriatic plaques contained 2-3 times more calmodulin than the skin of normal controls when examined on a per micrograms of DNA, per micrograms of protein, and per gram of wet weight basis. Adjacent uninvolved psoriatic skin also had significantly elevated calmodulin levels in all data bases except per microgram of protein/cm2. These data suggest that increased calmodulin levels are associated with epidermal hyperproliferation and/or with the state of differentiation. PMID- 2579164 TI - Ichthyosis vulgaris: identification of a defect in synthesis of filaggrin correlated with an absence of keratohyaline granules. AB - Ichthyosis vulgaris is an autosomal dominant disorder of keratinization characterized histologically by absent or reduced keratohyaline granules in the epidermis and mild hyperkeratosis. The basic defect in ichthyosis vulgaris is unknown. We have tested for the presence of filaggrin and its precursor, profilaggrin, in the epidermis of affected and unaffected individuals from 2 families with ichthyosis vulgaris and correlated its presence and relative quantity with ultrastructure findings in the same individuals. Filaggrin was present on stained sodium dodecyl sulfate gels and immunoblots of epidermal proteins from controls and unaffected family members. It was absent from the more severely affected individuals in each family and reduced in intensity in the less severely affected family members. Immunohistology in controls showed localization of filaggrin-related protein in the stratum corneum and within the granular layer. In contrast, tissue from affected individuals showed little or no reaction. Electron microscopic studies showed that keratohyaline granules were absent in 3 severely affected individuals, and reduced in number in the others. The relative amount of keratohyalin by electron microscopy correlated with the amount of filaggrin detectable on immunoblots. The stratum corneum was thicker than in normals but showed the typical "keratin pattern" staining suggesting that filaggrin is not essential for keratin filament aggregation and may have another function in vivo. We have demonstrated that the structural proteins, profilaggrin and filaggrin, are reduced or absent in 5 patients from 2 pedigrees with ichthyosis vulgaris. This biochemical abnormality correlates with the morphologic reduction in the amount of keratohyalin, and with the clinical severity of the disorder. PMID- 2579166 TI - Epidermal I-J-bearing cells are responsible for transferable suppressor cell generation after immunization of mice with ultraviolet radiation-treated epidermal cells. AB - Subcutaneous immunization of mice with hapten-coupled, ultraviolet radiation (UVR)-treated epidermal cells (EC) results in a hyporesponsive delayed-type hypersensitivity (DTH) response associated with the appearance of afferent acting, hapten-specific T suppressor (Ts) cells. Depletion of I-J-bearing cells from the EC population prior to UVR-exposure and hapten coupling prevents the appearance of these Ts cells. However, non-UVR-treated EC depleted of I-J-bearing cells and hapten-coupled are capable of immunizing mice for a DTH response. Therefore, the set of I-J-bearing EC appears to be distinct from classic Langerhans cells. A novel set of I-J-bearing EC appears to be responsible for Ts activation after subcutaneous immunization with hapten-coupled UVR-treated EC. PMID- 2579167 TI - Bullous pemphigoid antigen localization suggests an intracellular association with hemidesmosomes. AB - Autoantibodies to a normal component of stratified squamous epithelia, the bullous pemphigoid antigen (BPA), are synthesized in patients with the disease bullous pemphigoid. We have used these sera to study the distribution of BPA in vivo and in vitro. At low magnification, indirect immunofluorescent staining for BPA is linear at the basement membrane zone (BMZ) of skin and many other epithelial tissues. At higher magnification however, we observed a punctate staining pattern for BPA which was regular in appearance and suggested localization of BPA to discrete structures at the BMZ. Subsequent immunoelectron microscopy using both peroxidase and colloidal gold labeling techniques with patients' sera or IgG, revealed that BPA is associated with hemidesmosomes- putative adhesion structures at the BMZ, based on their similarity in ultrastructure to desmosomes. More specifically BPA was immunolocalized to the cytoplasmic face of hemidesmosomes and was not observed extracellularly in the basement membrane. In stratifying and nonstratifying cultures of rat keratinocytes, BPA is expressed intracellularly and not in the cell-derived matrix, unlike other known basement membrane components. These cells also synthesize BPA in vitro, and immunoprecipitation from metabolically labeled cultures revealed a 220 kD polypeptide under reducing conditions. From these observations we conclude (1) that BPA is a 220 kD polypeptide component either of or associated with hemidesmosomes, and (2) that it is localized intracellularly both in vivo and in vitro. We suggest that BPA is not normally a lamina lucida component, but that it may form part of a linkage between the cytoskeleton and the basement membrane. PMID- 2579168 TI - Effect of actinomycin D on the expression of nuclear antigen SS-B/La. AB - The nuclear autoantigen SS-B/La, which is recognized by antibodies in certain autoimmune diseases, is complexed with distinct cellular RNAs and the complex of antigen-RNA profile remains constant throughout the cell cycle. This antigen is prominent in the nucleolus during G1/S phase of the cell cycle. Actinomycin D at a concentration of 0.0005 microgram/ml is capable of abolishing the appearance of SS-B/La in the nucleolus. The amount of immune-precipitable SS-B/La-associated RNAs is reduced by 0.005 microgram/ml actinomycin D treatment. The mechanism for these findings is suggested to be related to inhibition of the synthesis of messenger RNA coding for SS-B/La. PMID- 2579169 TI - Antigenic characterization of respiratory syncytial virus strains with monoclonal antibodies. AB - To study the antigenic characteristics of respiratory syncytial virus (RSV), we developed and evaluated monoclonal antibodies (MAbs) to three strains of RSV: 11 to Long, 4 to 18537, and 9 to A2. Six of these MAbs immunoprecipitated the nucleoprotein, six the large glycoprotein, and 11 the fusion protein. By the pattern of the reactions of these MAbs to 16 strains of RSV in an indirect immunofluorescence assay or enzyme-linked immunosorbent assay, we were able to distinguish three subgroups. With a panel of 10 of these 24 MAbs, we tested 26 strains isolated between 1979 and 1982 in Boston and found that 22 belonged to group 1, 4 to group 2, and none to group 3. The pattern of the reactions of the MAbs against representative strains from the three groups identified nine epitopes by indirect immunofluorescence assay: three of each on the nucleoprotein, the large glycoprotein, and the fusion protein. These results, along with those of previous studies, suggest that groups 1 and 3 are antigenically similar and group 2 is antigenically more distinct. PMID- 2579170 TI - Antigenic analysis of a putative new strain of respiratory syncytial virus. AB - A recent isolate (9320) of respiratory syncytial virus (RSV) that had been reported to differ from all previous strains was compared with RSV strains isolated over a period of 23 years by using the techniques of in vitro neutralization by specific antiserum and in vivo resistance to infection in cotton rats. The 9320 strain did not appear to be a novel antigenic variant and exhibited greater homology to several prototype strains than did an earlier isolate. The antigenic differences detected by in vitro neutralization disappear when virus strains are compared in vivo. Thus, it appears that concerns that antigenic instability might compromise efforts at RSV prophylaxis are unfounded. PMID- 2579171 TI - The more things change ... PMID- 2579172 TI - Immunohistochemical demonstration of amylase in endometrioid carcinomas of the ovary. PMID- 2579173 TI - Capacity for amylase production of endometrial carcinomas. PMID- 2579174 TI - Neovascularization produced by angiotensin II. AB - Following vascular occlusion, development of collateral circulation occurs in at least two time-related phases: (1) the fast enhancement of the function of preexisting channels and (2) the slow formation of new vessels. Inasmuch as the renin-angiotensin system can act as a protective mechanism against local ischemia by activating preexisting collateral vessels, it is of interest to establish whether angiotensin II also produces stimulation of new vessel formation. Angiotensin II or cholecystokinin, an unrelated peptide, was incorporated in a slow-release formulation polyacrylamide gel and implanted in a pocket made in the rabbit cornea. Periodic examinations revealed that angiotensin II significantly stimulates new vessel formation; maximum values were attained in approximately 2 to 3 weeks. In contrast, cholecystokinin or polyacrylamide gel alone failed to stimulate any significant new vessel formation. Positive neovascularization was present in 85% of the total number of corneas implanted with angiotensin II, whereas 14% and 8% positive results were seen in the corneas implanted with either cholecystokinin or polyacrylamide gel alone, respectively. It is concluded that angiotensin II not only facilitates the activation of preexisting collateral vascular pathways but also has angiogenic properties and therefore could play an active role not only in the fast but also in the slow phase of the development of collateral circulation. PMID- 2579175 TI - Quantitative analysis of alkaline phosphatases in serum and amniotic fluid: comparison of biochemical and immunologic assays. AB - An immunoprecipitation method using monoclonal antibodies specific for the three categories of alkaline phosphatases, liver/bone/kidney, placental, and intestinal, is described and compared with the heat denaturation-chemical inhibition method for quantitating the contributions of the various isoenzymes to the total activity in biologic fluids. Activity values for the three categories of isoenzymes present in normal and pregnancy sera as well as in early gestation amniotic fluids were determined by both methods. There is very close correlation between the values obtained by both methods. Thus, two independent procedures are now available for quantitating the contributions of the various alkaline phosphatase isoenzymes in biologic fluids. PMID- 2579176 TI - Testicular lesions in Whipple's disease. AB - In two patients with Whipple's disease a variety of abnormalities were found in the testis. In both there was a thickened tunica albuginea containing macrophages filled with Schiff-positive bacilli, and both exhibited Whipple bacilli alone or in small clumps within the tunica media of the testicular arteries. One patient had focal inflammatory lesions among the Leydig cells. The most prominent abnormality in each was the abundance of Whipple bacilli within the epithelium of the seminiferous tubules. Some of these bacilli (which were free rather than within macrophages) appeared to be being shed into the tubular lumen; there was no associated inflammation. In some areas macrophages filled with bacilli appeared to migrate from the arterial adventitia toward the seminiferous tubules. Potential significance of these findings is discussed relative to a variety of testicular and prostatic diseases, as well as the possible (and arguable) relationship to the acquired immune deficiency syndrome. PMID- 2579177 TI - Platelet release in coronary heart disease: effect of antiplatelet drugs and coronary artery bypass graft. AB - We report serial measurements of in vivo platelet release products beta thromboglobulin and platelet factor 4 in 38 patients with coronary artery disease who underwent coronary artery bypass graft surgery. All patients were given dipyridamole preoperatively and both dipyridamole and aspirin postoperatively. Assays of plasma beta-thromboglobulin and platelet factor 4 were performed immediately before surgery, at discharge, and at follow-up visits. At initial evaluation, 22 patients with prior myocardial infarction had significantly elevated plasma beta-thromboglobulin levels (p = 0.0004). In the preoperative period, the use of dipyridamole caused some reduction of plasma beta thromboglobulin and platelet factor 4, but the difference was not statistically significant. Six to 12 days after surgery, all patients had plasma beta thromboglobulin concentrations higher than the preoperative levels despite the continued ingestion of dipyridamole and aspirin. At a follow-up visit, 30 to 133 days after surgery, only patients with previous myocardial infarction had beta thromboglobulin levels higher than their preoperative values. However, compared with controls, all patients who underwent coronary artery bypass graft surgery had elevated plasma levels of beta-thromboglobulin in both the early and late postoperative periods. In this group of patients, successful revascularization of the myocardium, as indicated by relief of symptoms, did not completely inhibit platelet activation. PMID- 2579178 TI - Interferon production in murine macrophage-like cell lines. AB - Five murine macrophage (M phi)-like cell lines were examined to determine their suitability for the characterization of M phi interferons (IFNs). The J774A.1, RAW 309 Cr.1, and RAW 264.7 cell lines produced 30-800 international units (IU)/10(6) cells when treated with 5-200 micrograms of bacterial lipopolysaccharide (LPS). No IFN was detected in LPS-treated P388D1 or PU5-1.8 cell cultures. All cell lines produced IFN when inoculated with Newcastle disease virus (NDV); however, only 15 IU/10(6) cells of acid stable IFN were produced in PU5-1.8 cell cultures in comparison to 4.2 X 10(3)-1.7 X 10(4) IU/10(6) cells in the other cell lines. Most of the IFN was produced within 4 h in LPS-treated cell cultures and within 12 h in NDV-infected cell cultures. All IFNs were stable at pH 2.0 and were neutralized with antiserum against mouse L cell IFN. These cell lines appear competent for use in studying the synthesis, molecular weights, and regulatory functions of M phi IFNs. PMID- 2579179 TI - Overdrive excitation and cellular calcium load in canine cardiac Purkinje fibers. AB - The induction of spontaneous activity by drive ("overdrive excitation") was studied by means of a microelectrode technique in canine cardiac Purkinje fibers exposed to an enhanced calcium load. The following results were obtained: 1) in quiescent fibers, a single action potential is followed by a prolonged transitory depolarization ("slow afterdepolarization") that may initiate a slow spontaneous rhythm; 2) during short drives, the maximum diastolic potential (Emax) gradually decreases and diastolic depolarization becomes steeper due to a superimposed oscillatory potential of progressively greater amplitude; 3) after the drive, the oscillatory potential either initiates a fast repetitive activity or is followed by a slow repolarization to the original resting level; 4) the cessation of induced activity is associated with an increase in Emax; 5) during longer and faster drives, Emax increases and the oscillatory potential becomes smaller, peaks sooner and may fail to excite; 6) repetitive activity may also be induced at a depolarized level. We conclude that overdrive excitation involves an increased cellular calcium, can occur at normal or depolarized levels, and is induced by an oscillatory potential superimposed on a slow afterdepolarization. It is most easily initiated by a short and fast drive because at that time the oscillatory potential and slow afterdepolarization are optimally combined to induce activity. PMID- 2579180 TI - Electrocardiographic criteria for differentiating aberrancy and ventricular extrasystole in chronic atrial fibrillation: validation by intracardiac recordings. AB - Many electrocardiographic criteria have been proposed for the differentiation of ventricular extrasystole and supraventricular conduction with aberrancy in atrial fibrillation but the validity of these have not been confirmed by intracardiac studies. We recorded His bundle electrograms in nineteen patients (eleven men, eight women) referred for diagnosis of abnormal QRS complexes in the context of chronic atrial fibrillation. Of 1,068 wide QRS complexes analyzed, 91% proved to be of ventricular origin. Electrocardiographic criteria which were specific for ventricular extrasystole included: left bundle branch block morphology, right bundle branch block morphology with a monophasic R in lead V1 or an RS or QS pattern in lead V6, presence of a "compensatory pause", i.e., compensatory cycle (V2-V3) longer than the average cycle length of ten normally conducted beats preceding the abnormal complex (927 +/- 317 vs 780 +/- 199, mean +/- SD in msec. p less than 0.005), frontal QRS axis of the abnormal complex directed superiorly or to the right and the presence of a "short-long" cycle sequence. Right bundle branch morphology with a triphasic R in lead V1 or QRS pattern in V6 and concordant initial vector in lead V1 or in more than one ECG leads were very specific for supraventricular conduction with aberrancy. Analysis of coupling interval and Ashman's phenomenon, i.e., the long-short cycle sequence, were not specific for supraventricular conduction with aberrancy. We conclude that in digitalis-treated patients with chronic atrial fibrillation the majority of abnormal QRS complexes are of ventricular origin. The diagnosis of ventricular extrasystole or aberrancy can be made using a single ECG lead (V1) and applying a combination of easily applied criteria. PMID- 2579182 TI - Effects of 5-hydroxytryptamine uptake blockers on the concentration in brain of 5 hydroxytryptamine and 5-hydroxyindoleacetic acid in male rats, pro-oestrous rats and ovariectomized rats treated with oestrogen and progesterone. AB - The aim of this study was to determine the effect of 5-hydroxytryptamine (5-HT) uptake blockade on 5-HT turnover by measuring the concentrations of 5-HT and 5 hydroxyindoleacetic acid (5-HIAA) in brain with the aid of high performance liquid chromatography and electrochemical detection. The indoleamines were measured in the anterior hypothalamus (AH), posterior hypothalamus (PH) and raphe nuclei 30 min after the i.v. injection of either alaproclate (30 mg/kg) or zimelidine (20 mg/kg). The effect of alaproclate was studied in male rats, pro oestrous female rats, rats ovariectomized and injected s.c. with 20 micrograms oestradiol benzoate (OB) on dioestrus and at 12.00 h of the next day (presumptive pro-oestrus) with 2 mg progesterone (model 1) and rats ovariectomized 3-4 weeks before an s.c. injection of 20 micrograms OB followed 72 h later by an s.c. injection of 2 mg progesterone (model 2). Alaproclate caused a significant decrease in the 5-HIAA/5-HT ratio in the AH and PH of the brain of male rats, in the PH and raphe nuclei in pro-oestrous rats and model 1, and in the raphe nuclei alone in model 2. Zimelidine had no effect on the 5-HIAA/5-HT ratio in any area in model 2. In male rats the injection of parachlorophenylalanine produced a marked reduction in the brain concentrations of 5-HT and 5-HIAA, but the 5-HIAA/5 HT ratio was unchanged by a subsequent injection of alaproclate. None of the pharmacological agents affected significantly the brain concentrations of noradrenaline, dopamine or dihydroxyphenylacetic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579181 TI - Ventricular arrhythmias following one-stage and two-stage coronary reperfusion: evidence for both reentry and enhanced automaticity. AB - We studied the effects of reperfusion in 60 dogs following a 30-45 minute period of left anterior descending coronary artery occlusion using electrocardiograms and composite electrogram recordings. One-stage reperfusion in 14 of 15 dogs produced ventricular arrhythmias which degenerated into ventricular fibrillation within 60 seconds. The onset of ventricular arrhythmias was associated with continuous electrical activity in epicardial and intramural electrograms recorded from the reperfused zone. Vagal slowing during reperfusion (64 +/- 8/min) did not prevent ventricular fibrillation (eight of eight dogs) and escape beats were often followed by one or more coupled ectopic beats associated with continuous electrical activity. Rapid atrial pacing (270/min) also did not prevent the appearance of ventricular arrhythmia with associated continuous electrical activity and ventricular fibrillation (six of six dogs) nor did 4 mg/kg lidocaine (15 of 16 dogs). In another group of 15 dogs reperfusion was performed in two stages resulting in no ventricular fibrillation but in 8 of 15 dogs ventricular arrhythmias were observed beginning within two minutes after reperfusion and lasting 20-30 minutes. These ventricular arrhythmias were not associated with continuous electrical activity in any of the recorded leads. Atrial pacing suppressed ventricular arrhythmias and idioventricular rate averaged 157 +/- 10/min versus 55 +/- 10/min pre-reperfusion control. The earliest site of activation indicated automatic foci arising in the subendocardium of the reperfused zone. Lidocaine (2-4 mg/kg) rapidly (less than 90 sec) restored normal sinus rhythm and suppressed automaticity (72 +/- 11/min) as did left anterior descending artery reocclusion (52 +/- 6/min). We conclude that both reentry and enhanced automaticity play a role in ventricular arrhythmias due to reperfusion. Lidocaine (2-4 mg/kg) suppresses automatic but not reentrant ventricular arrhythmias in this experimental setting. PMID- 2579183 TI - Responses to prolactin secretagogues in oestrogen-treated rats suggest that the defect in prolactin regulation produced by oestrogen is at the level of the pituitary gland. AB - Prolactin responses to pharmacological agents were used to characterize the defect in prolactin regulation which occurs after administration of high doses of oestrogen to rats. Animals with chronically implanted venous cannulae were injected with 2 mg oestradiol benzoate in oil and 2-3 days later prolactin concentrations were measured after injections of saline, thyrotrophin-releasing hormone (TRH), fenfluramine, apomorphine and butaclamol. The responses were compared with those in oil-injected animals. Hyperprolactinaemia in oestrogen treated animals was unresponsive to apomorphine, but was even more sensitive to dopamine receptor blockade than controls. These results suggest that the lactotrophs in oestrogen-treated animals are already maximally suppressed by endogenous dopamine, though ineffectively. Although there was an increased prolactin response to TRH in oestrogen-treated animals, there was an impaired response to fenfluramine, indicating suppressed serotonergic prolactin-releasing factor mechanisms. Maximal endogenous dopaminergic activity and suppressed prolactin-releasing factor mechanisms are appropriate hypothalamic responses to hyperprolactinaemia. The operation of these responses in the earliest stages of the development of pituitary hyperplasia indicates that oestrogen induces a disturbance of prolactin regulation in the lactotroph, independent of hypothalamic control. PMID- 2579184 TI - Human immune response to group A streptococcal carbohydrate (A-CHO). I. Quantitative and qualitative analysis of the A-CHO-specific B cell population responding in vitro to polyclonal and specific activation. AB - The immune response to the group-specific carbohydrate of group A streptococci (A CHO) provides an informative in vitro model for the investigation of several aspects of human anticarbohydrate immune responses. A-CHO-specific B cells can be polyclonally activated by pokeweed mitogen (PWM), and, specifically, by in vitro immunization with streptococcal vaccine. High levels of A-CHO-specific antibodies, mainly directed to the immunodominant side chain N-acetyl-D glucosamine (GlcNAc), occur in healthy adult individuals. Serum antibody levels are reflected in high frequencies of precursor B cells among peripheral blood lymphocytes. In one particular case, greater than 15% of all B cells activated by PWM for IgM production were found to produce IgM anti-A-CHO antibodies, as determined in limiting dilution experiments, as well as by analyzing Ig concentrations in bulk culture experiments. The case with the lowest proportion observed had 0.3% A-CHO-specific B cells among IgM-producing B cells. Preferential PWM activation of anti-A-CHO-producing B cells could be excluded. The comparison of the proportions of anti-A-CHO IgM produced in vivo, and of B cells producing antibodies of this specificity in peripheral blood, suggests a similar distribution of specific precursor B cells in the antibody-producing lymphoid tissue compartments and in peripheral blood. However, nearly all specific antibodies produced in vitro belong to the IgM isotype, whereas IgG anti A-CHO in high amounts, mostly exceeding the specific IgM, was found only among anti-A-CHO antibodies produced in vivo. Low anti-A-CHO IgG production was seen in polyclonally activated as well as in antigen-activated cultures, whereas, in contrast, total IgG was produced in considerable amounts after polyclonal activation. This suggests a different distribution pattern, and/or diverse differentiation requirements for anti-A-CHO-producing B cells, compared with other B cell species. PMID- 2579185 TI - Bone marrow graft rejection as a function of antibody-directed natural killer cells. AB - There is conclusive evidence that acute bone marrow transplant rejection in lethally irradiated mice is caused by natural killer (NK) cells. The rejection of marrow allografts is exquisitely specific and is controlled by antigenic determinants encoded in or near the H-2 gene complex. The specificity of in vivo marrow graft rejection contrasts with the in vitro specificity pattern of NK cells in cytotoxicity assays. We therefore examined how NK cells cause H-2 specific marrow graft rejection in vivo. Several experimental approaches are presented that suggest that natural antibody, present in responder strains of mice, specifically directs NK cells in an antibody-dependent cytolytic and/or cytostatic reaction, resulting in marrow graft rejection. The following evidence for this mechanism is documented. The ability to reject a marrow graft can be passively transferred by serum from responder to allogeneic nonresponder mice and the specificity of rejection can be mapped within the H-2 region. Serum-induced marrow graft rejection is abrogated following depletion of immunoglobulin, and the serum of responder mice is able to induce a specific antibody-dependent cytotoxic reaction in vitro. PMID- 2579189 TI - Influence of the uterine environment on rat sperm motility and swimming speed. AB - The present study compared several rat sperm parameters in semen samples recovered from a natural uterine environment (i.e., intact estrous female) to those recovered from an artificially induced uterine environment (i.e., ovariectomized hormonally primed female). The sperm parameters measured were percent motile, percent exhibiting forward progressive motility, actual swimming speed, and linear swimming speed. The comparisons were conducted at four postcopulatory time points (0.25, 1.5, 3, and 6 hours) in order to detect differences as a function of residence time within the uterus. No significant differences (P less than 0.05) in the parameters were seen between the two types of uterine environments. Residence time within the reproductive tract had no significant effect on the parameters with the exception of percent motile, which was significantly increased (P less than 0.01) at the 1.5-hour postcopulatory time point. PMID- 2579186 TI - Induction of immunoglobulin isotype switching in cultured I.29 B lymphoma cells. Characterization of the accompanying rearrangements of heavy chain genes. AB - The murine B cell lymphoma I.29 contains cells expressing surface IgM or IgA with identical heavy chain variable regions (9, 25, and D. Klein and J. Stavnezer, unpublished data). Purified IgM+ cells from the lymphoma have been adapted to culture and induced to switch to IgA, IgE, or IgG2 by treatment with lipopolysaccharide (LPS) or by treatment with a monoclonal anti-I.29 antiidiotype plus LPS. Clones of IgM+ cells have been obtained and induced to switch. Under optimal conditions, 30% of the cells in the culture expressed IgA 8 d after the inducers were added, and by 15 d 90% of the cells were IgA+. In actively switching cultures, up to 50% of the cells whose cytoplasm stained positively with anti-IgA stained simultaneously with anti-IgM, which indicates that the appearance of IgA+ cells in the cultures was due to isotype switching and not to clonal outgrowth. Examination by Southern blotting experiments of the Ig heavy chain genes in I.29 cells before and after switching revealed that isotype switching was accompanied by DNA recombinations that occurred within or immediately 5' to the tandemly repeated switch sequences. Within 3 d after the addition of inducers of switching, the nonexpressed chromosome underwent a variety of deletions or expansions within the S mu region, and a portion of the S alpha regions had undergone a 0.9-kb deletion. In cultures that contained at least 12% IgA+ cells, rearranged, expressed alpha genes, produced by recombination between the S mu region within the expressed mu gene and the S alpha region, were detected. PMID- 2579187 TI - Location of variable and conserved epitopes among the multiple serotypes of streptococcal M protein. AB - In studies primarily confined to the amino-terminal region of the fibrillar group A streptococcal M protein, only limited immunological crossreactions have been observed among M serotypes. In this investigation, two monoclonal antibodies generated against nearly the entire M6 molecule (LysM6) were used to determine the extent of crossreactions among M serotyping strains and to localize their epitopes on the M molecule. Colony blot and immunoblot analyses revealed that an epitope responsible for crossreactions among 5 of the 56 strains of different M serotypes tested is located in the amino-terminal half of the molecule, distal to the cell surface. In contrast, a more common crossreactive epitope, reacting with 20 of the 56 strains, is located near the middle of the M molecule. These studies also reveal that the more conserved determinant, located more proximally to the cell surface, is accessible to the immune system, even on the whole organism, and, thus, may be useful in devising means to protect against infections by multiple group A streptococcal M serotypes. PMID- 2579188 TI - On the use of alpha-amanitin as a transcriptional blocking agent in mouse embryos: a cautionary note. AB - We have tested the effect of alpha-amanitin at 10, 50 and 100 micrograms/ml, on precursor uptake and incorporation into poly(A)+ RNA and poly(A)- RNA of mouse embryos on days 2, 3 and 4 of gestation. Embryos were pretreated with the inhibitor for 2 hr, then labeled for 2 hr in its continued presence. RNA fractions were separated by affinity chromatography on oligo(dT)-cellulose. alpha Amanitin did not suppress uptake of RNA precursors at any of the concentrations tested in any stage. At 10 micrograms/ml, we could not detect any effect on incorporation into either RNA fraction in any stage. Only the highest concentration tested, 100 micrograms/ml, was effective in all stages in substantially suppressing incorporation into poly(A)+ RNA within 2 hr. Longer treatments increased the level of suppression to a maximum of about 80%. Incorporation into poly(A)- RNA was suppressed to roughly the same extent. Despite previously reported data, it cannot be assumed that alpha-amanitin at concentrations less than 100 micrograms/ml brings about a quick interruption of mRNA synthesis in preimplantation mouse embryos. PMID- 2579190 TI - Autoradiographic studies on the distribution of labeled maternal RNA in early mouse embryos. AB - Maternal RNA of mouse eggs and embryos was labeled by exposure of growing ovarian oocytes to 3H-uridine in vivo 8 to 16 days before ovulation and fertilization. Labeled embryos from the 1-cell stage to the blastocyst stage were collected, fixed, and autoradiographs of plastic sections prepared. The observed grain density was similar in the pronuclei and in the cytoplasm of 1-cell embryos. Knowing the volumes of nucleus and cytoplasm, it was determined that 3% of the maternal RNA was found in the pronuclei. It is suggested that some of this nuclear RNA may be stable small nuclear RNAs (e.g. U1 RNA) retained from the germinal vesicle stage through meiotic maturation. During the 2-cell stage and beyond, maternal RNA is degraded and labeled precursor is reincorporated into nuclear RNA, making it difficult to accurately quantitate the amount of nuclear maternal RNA. It is known that about one third of the total maternal RNA is lost between the 8-cell and blastocyst stages. It was found that cytoplasmic grain densities in inner and outer cells of the morula and blastocyst were not significantly different. Thus, the loss of maternal RNA does not proceed more rapidly in the differentiating trophoblast than in the inner cell mass. PMID- 2579191 TI - Preparation and characterization of monoclonal antibodies directed against four structural components of canine distemper virus. AB - Mouse hybridomas producing antibodies against structural proteins of canine distemper virus (CDV) were produced by fusion of Sp2/0 myeloma cells with spleen cells from BALB/c mice immunized with purified preparations of Vero cell-grown CDV. Ascites fluids collected after intraperitoneal inoculation with 149 CDV antibody-producing hybridoma cell lines were characterized by different serological tests. By immune precipitation tests with [35S]methionine-labelled extracellular virions and intracellular virus polypeptides, 57 clones were found to produce antibodies against the nucleocapsid protein (NP), 22 against the polymerase (P) protein, 10 against the fusion (F) protein and nine against the large uncleaved glycoprotein (named H in analogy with measles virus). By competitive binding enzyme-linked immunosorbent assay (ELISA) tests with monoclonal antibodies against each structural component, a minimum of 18, six, three and seven separate antigenic determinants were identified on the NP, P, F and H proteins, respectively. The reactions of clones directed against F and H surface components of the virus were tested for their ability to inhibit the infectivity of both CDV and measles virus in the absence and presence of anti gamma-globulin. In addition, the inhibitory activity of the clones on measles haemagglutinating (HA) and haemolysis (HL) activity were examined. Monoclonal antibodies against six of the seven antigenic determinants of the H protein could neutralize the infectivity of the virus. After addition of anti-gamma-globulin to the test, increases of titres varying from twofold to several hundredfold were observed with the different clones. None of all the clones against H could block measles virus infectivity, HA or HL activity. The 10 clones directed against the F protein could not neutralize the infectivity of CDV even in the presence of anti-gamma-globulin. Further, the antibodies could not inhibit measles HA and HL activity in the absence of anti-gamma-globulin. However, after the addition of anti-gamma-globulin, antibodies against two of the three sites were found to block measles virus HL activity. The reactions of all clones were tested in immune fluorescence, ELISA and immune precipitation tests with three strains of CDV. Each strain had a few unique antigenic sites. Variation was found in four, one and three different antigenic sites of the NP, P and H proteins, respectively. PMID- 2579193 TI - Effect of the cerebral tryptaminergic system on the turnover of dopamine in the striatum of the rat. AB - The effect of the cerebral 5-hydroxytryptamine system on the turnover of striatal 3,4-dihydroxyphenyl-ethylamine (dopamine) was investigated by measuring the level of dopamine and one of its metabolites in rats depleted of cerebral 5 hydroxytryptamine or treated with a 5-hydroxytryptamine receptor blocker. Treatment with p-chlorophenylalanine induced, in addition to a reduction in striatal 5-hydroxytryptamine and 5-hydroxyindol-3-ylacetic acid, an increase in the striatal concentration of dopamine, a diminution in the concentration of homovanillic acid in the same cerebral area, and a reduction in the rise of this acid after the administration of a butyrophenone derivative or tetrabenazine. Treatment with methysergide also reduced the increase of homovanillic acid induced by the butyrophenone. When probenecid was given to rats treated with p chlorophenylalanine, homovanillic acid failed to accumulate, whereas the accumulation of 5-hydroxyindol-3-ylacetic acid was unaffected. The decay of dopamine after alpha-methyl-p-tyrosine administration was normal for the first 6 h but was later reduced in rats given p-chlorophenylalanine or methysergide. The results suggest that the lack of activation of 5-hydroxytryptamine receptors leads to a reduction in the turnover of dopamine in the nigrostriatal pathway. PMID- 2579192 TI - Treatment of chronic type B hepatitis with multiple ten-day courses of adenine arabinoside monophosphate. AB - Ten patients with chronic type B hepatitis were treated with three courses of adenine arabinoside monosphosphate (Ara-AMP). The drug was given intramuscularly at a dosage of 10 mg/kg/day in ten-day courses during each of three sequential months. The patients were all men, aged 31-61 years, who were known to have had chronic hepatitis for one to four years. Each of the ten-day courses of Ara-AMP was accompanied by a marked inhibition in the serum levels of hepatitis B virus (HBV) DNA and DNA polymerase activity. However, HBV-DNA remained detectable in every patient during treatment and invariably rebounded to pretreatment levels soon after each course was stopped. One patient developed severe, and two patients developed mild neuromuscular side effects. During a 12-18-month follow up period, only one of the ten patients has had a sustained clinical, serum biochemical, and serological remission. In this patient, serum HBeAg, HBV-DNA, and DNA polymerase became undetectable three months after the final course of treatment; serum aminotransferase levels subsequently fell into the normal range; and a follow-up liver biopsy showed a diminution in the chronic inflammatory cell activity and a disappearance of intrahepatic hepatitis B core antigen reactivity. Thus, multiple ten-day courses of Ara-AMP do not induce a high rate of remissions in this disease and are associated with appreciable neuromuscular toxicity. Ara AMP is a potent inhibitor of serum levels of hepatitis B virus, but Ara-AMP therapy has not been shown to have long-term beneficial effects in chronic type B hepatitis. PMID- 2579194 TI - Immunohistochemical localization of 2',3'-cyclic nucleotide 3'-phosphodiesterase and myelin basic protein in the central nervous system of the jimpy and the normal mouse. AB - We describe the immunohistochemical localization of 2',3'-cyclic nucleotide 3' phosphodiesterase (CNPase) and myelin basic protein (MBP) in CNS of the jimpy mutant mouse which is characterized by dys- and demyelination. In controls, the CNPase and MBP were localized exclusively in white matter in the CNS. The jimpy mutant mice were severely affected: A very weak reaction was observed in the white matter. Very few CNPase- and MBP-positive myelin sheaths were observed, and some degradation products were also observed after reaction with antisera against both CNPase and MBP. The immunohistochemical reaction in the jimpy mice showed a similar localization in both CNPase and MBP. PMID- 2579195 TI - Molecular genetic analysis of myelin-deficient mice: shiverer mutant mice show deletion in gene(s) coding for myelin basic protein. AB - The gene expression of myelin basic proteins (MBPs) in shiverer mutant mice was investigated by the Northern and Southern hybridization techniques. In the control mice RNA molecules from the brains which were about 2,300 nucleotides in length were hybridized to cDNA of 1.8 kb encoding for a mouse MBP, but RNA from the brains of 3-week-old shiverer mutant mice contained no detectable amount of MBP transcripts hybridizing to this probe. Moreover the shiverer mutant mice lost several restriction fragments that hybridized to the same probe in the control mice when each of the five restriction enzymes, i.e., HindIII, PstI, PvuII, AccI, and StuI, was used. These data suggest that the shiverer mutation may correspond to the deletion of a large portion of MBP exon(s) in the gene, and this deletion causes inefficient transcription leading to the depletion of MBPs in the myelin and the dysmyelination observed in these mice. PMID- 2579196 TI - Measurement of substance P metabolites in rat CNS. AB - A procedure based on ion-exchange chromatography for chemical separation and radioimmunoassays for quantitation of substance P (SP), the SP(1-7), and C terminal fragments, respectively, has been developed. The procedure allows the determination of these fragments in the presence of large (i.e., 50- to 100-fold) excess of parent compound. The chemical identity of isolated SP and fragments was studied with preparative electrophoresis on dilute agarose gel and with HPLC. The activity identified as SP(1-7) comigrated with the authentic standard whereas practically all activity isolated as C-terminal fragments comigrated with SP(5 11). The levels of C-terminal fragments in rat brain areas rich in SP and in spinal cord were 1-2% of those of parent compound. The levels of SP(1-7) were always higher, in the spinal cord markedly higher (three to five times). Postmortem storage of samples from brain and spinal cord indicated that SP(1-7) levels fell more rapidly than those of SP or C-terminal fragments. PMID- 2579197 TI - Myelin-associated glycoprotein and other proteins in Trembler mice. AB - The myelin-associated glycoprotein (MAG) and other myelin proteins were quantitated in homogenates of whole sciatic nerve from adult and 20-day-old Trember mice. In the nerves of adult mice, the concentration of MAG was increased from 1.1 ng/micrograms of total protein in the controls to 1.4 ng/micrograms protein in the Tremblers. By contrast, the concentrations of P0 glycoprotein and myelin basic proteins were reduced to 27% and 20% of control levels, respectively. Immunoblots demonstrated that P2 was also greatly reduced in the Trembler nerves. The specific activity of 2',3'-cyclic nucleotide 3' phosphodiesterase (CNP) was 65% of the control level. Immunoblot analysis showed that MAG had a higher than normal apparent Mr in the sciatic nerves of the Trembler mice, but its apparent Mr was normal in the brains of these mutants. In 20-day-old Tremblers, the P0 and myelin basic protein were reduced slightly less to about 40% of the level in the nerves of age-matched controls. CNP and MAG levels were not significantly different from those in controls, and MAG exhibited a shift toward higher apparent Mr similar to that in the adults. The maintenance of high MAG levels despite the severe deficit of myelin, as reflected by the decrease of the major myelin proteins, is consistent with the immunocytochemical localization of MAG in periaxonal Schwann cell membranes, Schmidt-Lantermann incisures, lateral loops, and the outer mesaxon and its absence from compact myelin. The abnormal form of MAG in the peripheral nervous system (PNS) of the Trembler mice may contribute to the pathology in this mutant. PMID- 2579199 TI - Expression of A1 adenosine receptors modulating dopamine-dependent cyclic AMP accumulation in the chick embryo retina. AB - Dopamine and 2-chloroadenosine independently promoted the accumulation of cyclic AMP in retinas from 16-day-old chick embryos. The two compounds added together either in saturating or subsaturating concentrations were not additive for the accumulation of the cyclic nucleotide in the tissue. This fact was shown to be due to the existence of an adenosine receptor that mediates the inhibition of the dopamine-dependent cyclic AMP accumulation in the retina. Adenosine inhibited, in a dose-dependent fashion, the accumulation of cyclic AMP induced by dopamine in 12-day-old chick embryo retinas, with an IC50 of approximately 1 microM. This effect was not blocked by dipyridamole. N6-(l-Phenylisopropyl)adenosine, (l-PIA) was the most potent adenosine analog tested, showing an IC50 of 0.1 microM which was two orders of magnitude lower than its stereoisomer d-PIA (10 microM). The maximal inhibition of the dopamine-elicited cyclic AMP accumulation by adenosine and related analogs was 70%. The inhibitory effect promoted by adenosine was blocked by 3-isobutyl-1-methylxanthine (IBMX) or by adenosine deaminase. Adenine was not effective; whereas ATP and AMP promoted the inhibition of the dopamine effect only at very high concentrations. Apomorphine was only 30% as effective as dopamine in promoting the cyclic AMP accumulation in retinas from 11- to 12-day old embryos and 2-chloroadenosine did not interfere with the apomorphine-mediated shift in cyclic AMP levels. In the retinas from 5-day-old posthatched chickens dopamine and apomorphine were equally effective in eliciting the accumulation of cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579198 TI - Comparison of three 18F-labeled butyrophenone neuroleptic drugs in the baboon using positron emission tomography. AB - The butyrophenone neuroleptics spiroperidol, benperidol, and haloperidol were radiolabeled with fluorine-18 and studied in baboon brain using positron emission transaxial tomography (PETT). Pretreatment of the baboon with a high pharmacological dose of (+)-butaclamol reduced the specifically bound component of radioactivity distribution in the striatum to approximately the radioactivity distribution found in the cerebellum. Comparative studies of brain distribution kinetics over a 4-h period indicated that either [18F]spiroperidol or [18F]benperidol may be suitable for specific labeling of neuroleptic receptors. In an 8-h study with [18F]spiroperidol, striatal radioactivity did not decline, suggesting that spiroperidol either has a very slow dissociation rate or that it binds irreversibly to these receptors in vivo. [18F]Haloperidol may not be suitable for in vivo PETT studies, because of a relatively high component of nonspecific distribution and a faster dissociation from the receptor. Analysis of 18F in plasma after injection of [18F]spiroperidol indicated rapid metabolism to polar and acidic metabolites, with only 40% of the total radioactivity being present as unchanged drug after 30 min. Analysis of the metabolic stability of the radioactively labeled compound in rat striatum indicated that greater than 95% of [18F]spiroperidol remains unchanged after 4 h. PMID- 2579200 TI - Methamphetamine-induced depression of monoamine synthesis in the rat: development of tolerance. AB - Animals treated with high doses of amphetamines have been used as a model of schizophrenia due to the similarities between the psychosis associated with this mental disorder and that induced by chronic amphetamine abuse. When administered to naive rats in high doses, the amphetamine-like CNS stimulant methamphetamine produces drastic alterations in the neurochemical parameters of the neostriatal monoaminergic systems. These alterations are characterized by a decrease in the activities of the rate-limiting enzymes for dopamine and serotonin synthesis, as well as a decrease in the concentrations of both neurotransmitters and their metabolites. However, tolerance develops to these neurochemical effects when drug administration occurs in a pattern similar to that encountered during chronic amphetamine abuse. The results indicate that the neurochemical alterations produced by amphetamines in naive and tolerant animals differ widely. This suggests that the administration of high doses of amphetamine-like central stimulants to naive rats may not be an appropriate model for studying the neurochemical changes associated with psychosis and amphetamine abuse. PMID- 2579201 TI - Drug potencies on partially purified brain D2 dopamine receptors. AB - To examine the sensitivities of partially purified dopamine receptors to various dopaminergic agonists and antagonists, canine brain striatum dopamine receptors were enriched by isoelectric focusing. The digitonin-solubilized receptors were prelabelled with [3H]spiperone and focused for two time periods. After 5 h (incomplete focusing), radioactive peaks were detected at pH 6 and 9-11. Only the pH 6 peak revealed drug sensitivities expected of D2 receptors. Receptor recovery of the pH 6 peak was 79% with purification being sevenfold. After focusing overnight to equilibrium, the pH 6 peak further separated into peaks at pH 4.6 and 6.8. The receptor was identified only in the pH 4.6 fraction. The recovery of receptors in the pH 4.6 peak was low (10%), indicating little enrichment of the receptor. The rank order of binding of neuroleptics and dopamine agonists to the purified material was similar to that of the original preparation of soluble receptors. Dopamine did not bind to the purified pH 4.6 fraction unless the phosphate buffer (used during focusing) was replaced with Tris buffer. The absence of receptors in the pH 6.8 and pH 10 fractions, although both contained prelabeled [3H]spiperone, indicates the importance of testing agonists and antagonists on each fraction at each step in purification. PMID- 2579202 TI - Regulation of serotonin release from the in vitro rat hippocampus: effects of alterations in levels of depolarization and in rates of serotonin metabolism. AB - We analyze the time course of 5-hydroxytryptamine (5-HT, serotonin) release from K+-depolarized hippocampal slices using a two-compartment kinetic model. The model is based on the assumptions that the rate of release is dependent on the amount of 5-HT in a releasable pool and that this pool may be resupplied during depolarization by newly synthesized 5-HT. Comparisons were made between predictions of the model and observed changes in 5-HT metabolism and in 5-HT release studied under a variety of experimental conditions. In accordance with predictions of the model, experimental manipulation of 5-HT synthesis and breakdown rates did not affect release immediately after depolarization but did affect the release rate during prolonged depolarization. Increasing bath tryptophan from 0 to 10 microM approximately doubled both 5-HT synthesis and the release rate after 40 min of K+-induced depolarization while having a smaller effect on release during the first 2 min. Inhibition of 5-HT breakdown did not significantly affect release during the first 2 min of depolarization but increased it over threefold after 40 min. In contrast, altering the concentrations of K+ or Ca2+ in the incubation medium affected mainly the early phase of 5-HT release and not the late phase. Reducing Ca2+ from 2.4 to 0.4 mM reduced 5-HT release by about 30% during the first 9 min of depolarization but did not affect release during the subsequent 30 min. Increasing the concentration of K+ from 18 to 60 mM stimulated release by sixfold during the first 2 min but only twofold after a subsequent 30 min. These results support our kinetic model and suggest that regulation of 5-HT metabolism at the site of the nerve terminal could be a mechanism for modulation of 5-HT release during prolonged discharge of serotonergic neurons. PMID- 2579203 TI - Changes in protein content of goldfish optic nerve during degeneration and regeneration following nerve crush. AB - After the goldfish optic nerve was crushed, the total amount of protein in the nerve decreased by about 45% within 1 week as the axons degenerated, began to recover between 2 and 5 weeks as axonal regeneration occurred, and had returned to nearly normal by 12 weeks. Corresponding changes in the relative amounts of some individual proteins were investigated by separating the proteins by two dimensional gel electrophoresis and performing a quantitative analysis of the Coomassie Brilliant Blue staining patterns of the gels. In addition, labelling patterns showing incorporation of [3H]proline into individual proteins were examined to differentiate between locally synthesized proteins (presumably produced mainly by the glial cells) and axonal proteins carried by fast or slow axonal transport. Some prominent nerve proteins, ON1 and ON2 (50-55 kD, pI approximately 6), decreased to almost undetectable levels and then reappeared with a time course corresponding to the changes in total protein content of the nerve. Similar changes were seen in a protein we have designated NF (approximately 130 kD, pI approximately 5.2). These three proteins, which were labelled in association with slow axonal transport, may be neurofilament constituents. Large decreases following optic nerve crush were also seen in the relative amounts of alpha- and beta-tubulin, which suggests that they are localized mainly in the optic axons rather than the glial cells. Another group of proteins, W2, W3, and W4 (35-45 kD, pI 6.5-7.0), which showed a somewhat slower time course of disappearance and were intensely labelled in the local synthesis pattern, may be associated with myelin. A small number of proteins increased in relative amount following nerve crush. These included some, P1 and P2 (35-40 kD, pIs 6.1-6.2) and NT (approximately 50 kD, pI approximately 5.5), that appeared to be synthesized by the glial cells. Increases were also seen in one axonal protein, B (approximately 45 kD, pI approximately 4.5), that is carried by fast axonal transport, as well as in two axonal proteins, HA1 and HA2 (approximately 60 and 65 kD respectively, pIs 4.5-5.0), that are carried mainly by slow axonal transport. Other proteins, including actin, that showed no net changes in relative amount (but presumably changed in absolute amount in direct proportion to the changes in total protein content of the nerve), are apparently distributed in both the neuronal and nonneuronal compartments of the nerve. PMID- 2579204 TI - Dopamine D2 receptors in the anterior pituitary: a single population without reciprocal antagonist/agonist states. AB - Although dopamine agonists can recognize two states of the D2 dopamine receptor in the anterior pituitary (D2high and D2low), we examined whether the dopamine antagonists such as [3H]spiperone could recognize these two sites with different affinities. Using up to 30 concentrations of [3H]spiperone, however, we could only detect a single population of binding sites (porcine anterior pituitary homogenates) with a dissociation constant (KD) of 130 pM. When specific [3H]spiperone binding was defined by a low concentration of (+)-butaclamol (100 nM), the apparent density was low. When defined by a high concentration of (+) butaclamol (10 microM), nonspecific sites became detectable, thus revealing two apparent populations of sites for [3H]spiperone, only one of which was specific for dopamine. Sodium chloride reduced the KD of the single population of specific D2 sites to 64 pM. Guanine nucleotide by itself had no effect on the KD, but enhanced the density by 25%. Since the density-enhancement could be eliminated by extensive washing of membranes, and could be restored by preincubation with dopamine, the nucleotide-induced elevation of D2 density appeared to be a result of the release of tightly bound endogenous dopamine. Thus, monovalent cations and guanine nucleotides appear to have separate regulatory effects on the anterior pituitary D2 receptor that modulate antagonist-receptor interactions. Several maneuvers were used to test whether [3H]spiperone could differentiate between the two agonist-detected subpopulations of sites. Twentyfold different concentrations of [3H]spiperone (47 pM and 1000 pM) were found to label identical proportions of receptors in the D2high and D2low states as detected by the agonist 6,7 dihydroxyaminotetralin (ADTN), suggesting that spiperone labelled equal proportions of D2high and D2low sites without differential affinity for them. In addition, competition of spiperone for D2high sites selectively labelled by the agonist [3H]n-propylnorapomorphine (NPA) had a virtually identical KD for spiperone as did the total D2 receptor population as determined by direct binding studies (75 pM versus 64 pM). [3H]Spiperone also bound to a uniform population of D2low sites induced by preincubation with guanine nucleotide with identical affinity as to the total D2 population. Thus, these data do not support a "reciprocal model" for the D2 receptor (i.e., antagonist having low affinity for D2high and high affinity for D2low in a manner reciprocal to agonists).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2579205 TI - Posttranslational protein modification: biosynthetic control mechanisms in the glycosylation of the major myelin glycoprotein by Schwann cells. AB - The posttranslational processing of the asparagine-linked oligosaccharide chain of the major myelin glycoprotein (P0) by Schwann cells was evaluated in the permanently transected, adult rat sciatic nerve, where there is no myelin assembly, and in the crush injured nerve, where there is myelin assembly. Pronase digestion of acrylamide gel slices containing the in vitro labeled [3H]mannose and [3H]fucose P0 after electrophoresis permitted analysis of the glycopeptides by lectin affinity and gel filtration chromatography. The concanavalin A-Separose profile of the [3H]mannose P0 glycopeptides from the transected nerve revealed the high-mannose-type oligosaccharide as the predominant species (72.9%), whereas the normally expressed P0 glycoprotein that is assembled into the myelin membrane in the crushed nerve contains 82.9-91.9% of the [3H]mannose radioactivity as the complex-type oligosaccharide chain. Electrophoretic analysis of immune precipitates verified the [3H]mannose as being incorporated into P0 for both the transected and crushed nerve. The high-mannose-type glycopeptides of the transected nerve isolated from the concanavalin A-Sepharose column were hydrolyzed by endo-beta-N-acetylglucosaminidase H, and the oligosaccharides were separated on Biogel P4. Man8GlcNAc and Man7GlcNAc were the predominant species with radioactivity ratios of 12.5/7.2/1.4/1.0 for the Man8, Man7, Man6, and Man5 oligosaccharides, respectively. Jack bean alpha-D-mannosidase gave the expected yields of free Man and ManGlcNAc from these high-mannose-type oligosaccharides. The data support the notion that at least two alpha-1,2-mannosidases are responsible for converting Man9GlcNAc2 to Man5GlcNAc2. The present experiments suggest distinct roles for each mannosidase and that the second mannosidase (I-B) may be an important rate-limiting step in the processing of this glycoprotein with the resulting accumulation of Man8GlcNAc2 and Man7GlcNAc2 intermediates. Pulse chase experiments, however, demonstrated further processing of this high mannose-type oligosaccharide in the transected nerve. The [3H]mannose P0 glycoprotein with Mr of 27,700 having the predominant high-mannose-type oligosaccharide shifted its Mr to 28,500 with subsequent chase. This band at 28,500 was shown to have the complex-type oligosaccharide chain and to contain fucose attached to the core asparagine-linked GlcNAc residue. The extent of oligosaccharide processing of this down-regulated glycoprotein remains to be determined. PMID- 2579206 TI - Calcium/ganglioside-dependent protein kinase activity in rat brain membrane. AB - The effects of gangliosides on phosphorylation were studied in rat brain membrane. Gangliosides stimulated phosphorylation only in the presence of Ca2+ with major phosphoproteins of 45,000, 50,000, 60,000, and 80,000 daltons and high molecular-weight species. In addition, gangliosides inhibited the phosphorylation of three proteins with molecular weights of 15,000, 20,000, and 78,000 daltons. The two low-molecular-weight proteins comigrated with rat myelin basic proteins. Ganglioside stimulation was dependent on the formation of a Ca2+-ganglioside complex since the calcium salt of gangliosides stimulated phosphorylation maximally. Disialo and trisialo gangliosides were more potent stimulators of kinase activity than the monosialo GM1 X GD1a was the most potent activator tested. Asialo-GM1, cerebroside, sialic acid, neuraminyllactose, sulfatide, and the acidic phospholipids phosphatidylserine and phosphatidylinositol did not stimulate kinase activity. The Ca2+-dependent, ganglioside-stimulated phosphorylation was qualitatively similar to the pattern for calmodulin-dependent phosphorylation. However, while calmodulin-dependent kinase activity was inhibited with an IC50 of 10 microM trifluoperazine, ganglioside-stimulated kinase was inhibited with an IC50 of 200 microM trifluoperazine. These results indicate that gangliosides have complex effects on membrane-associated kinase activities and suggest that Ca2+-ganglioside complexes are potent stimulators of membrane kinase activity. PMID- 2579207 TI - Monitoring the effect of a tryptophan load on brain indole metabolism in freely moving rats by simultaneous cerebrospinal fluid sampling and brain dialysis. AB - Rats were given L-tryptophan, 50 mg/kg i.p., and its concentration in the CNS was monitored in individual freely moving animals using repeated sampling of cisternal CSF and concurrent striatal dialysis. The 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid (5-HIAA) was also measured. Results were compared with changes of central tryptophan and 5-HIAA concentrations in brains of rats killed at various times after administration of L-tryptophan, 50 mg/kg i.p. Tryptophan changes in CSF were proportionate to those in whole brain and followed essentially identical time courses. Results for the striatal dialysate and whole striatum also paralleled each other. Similarly, results for 5-HIAA showed proportionality between CSF and brain and between dialysate and striatum. The data obtained were used to determine pharmacokinetic data for individual rats, i.e., areas under curves for both tryptophan and 5-HIAA and half-lives for the decline of tryptophan. Kinetic parameters varied considerably from rat to rat. However, mean half-lives for tryptophan in CSF, brain, dialysate, and striatum were all comparable. Results in general show the value of repeated CSF sampling and intracerebral dialysis for concurrent monitoring of changes of indole metabolism in the whole brain and a specific brain region, respectively. The methods should be suitable for the continuous monitoring of changes of central transmitter metabolism in parallel with observation of behavior following environmental or dietary changes or drug administration. They also should be of use in the investigation of drug kinetics in the CNS. PMID- 2579208 TI - Membrane disordering by anesthetic drugs: relationship to synaptosomal sodium and calcium fluxes. AB - The effects of membrane perturbants (ethanol, pentobarbital, chloroform, diethylether, phenytoin, cis-vaccenic acid methylester, and cis-vaccenoyl alcohol) on the lipid order of mouse brain synaptic plasma membranes (SPM) were tested by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a probe of the membrane core and 1-[4-(trimethylammonium)phenyl]-6-phenyl-1,3,5 hexatriene (TMA-DPH) as a probe of the membrane surface. The compounds decreased the fluorescence polarization of both probes, indicating that they disordered the membrane lipids. The decrease in polarization was, however, greater for DPH than for TMA-DPH, suggesting a greater effect on the membrane core than on the membrane surface. The voltage-dependent uptake of 24Na and 45Ca was studied in isolated mouse brain synaptosomes as a measure of membrane function. All of the compounds inhibited sodium influx, and their potencies for decreasing sodium uptake and fluorescence polarization of DPH were linearly correlated (r = 0.91). The relationship between changes in sodium influx and TMA-DPH polarization was less consistent (r = 0.66). Synaptosomal calcium uptake was inhibited by most, but not all, of the perturbants, but this inhibition was poorly correlated with changes in fluorescence polarization of DPH (r = 0.36) or TMA-DPH (r = 0.26). These results indicate that the function of synaptic sodium channels is correlated with lipid order in the hydrophobic core of the membrane and that the inhibitory effects of intoxicant-anesthetic drugs on neuronal sodium fluxes may be the result of their capacity to disorder these lipids. In contrast, the effects of drugs on voltage-dependent calcium channels were not clearly related to the capacity of these agents to disorder membrane lipids. PMID- 2579209 TI - Effects of rat ovariectomy on CSF monoamine metabolite levels and elimination. AB - Cerebrospinal fluid (CSF) was removed from the third ventricle of anesthetized male, female, and ovariectomized rats. CSF 3,4-dihydroxyphenylethylamine and serotonin metabolite levels [dihydroxyphenylacetic acid, homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA)] were determined on 15-min samples by liquid chromatography coupled with electrochemical detection. Monoamine oxidase inhibition was used for studying metabolite turnover in the CSF. No difference was observed between male, ovariectomized, and sham-operated female rats. However, ventricular CSF HVA and 5-HIAA levels were significantly higher in the ovariectomized than in the sham-operated rats. These differences do not reflect effects of ovariectomy on brain metabolite production but indicate slower metabolite elimination from the CSF. PMID- 2579210 TI - Immunohistochemical investigation of cerebral ischemia in gerbils. AB - Experimental cerebral ischemia was produced in gerbils by occlusion of the right common carotid artery in the neck. The evolution of the ischemic lesions was followed from five minutes to six hours by using the immunohistochemical techniques for tubulin and creatine kinase BB-isoenzyme. The earliest lesion was found in the subiculum-CA1 and CA2 regions of the hippocampus in five minutes. There was loss of staining in the apical dendrites and perikarya of the pyramidal cells. The earliest lesion in the cerebral cortex, visible in ten minutes, was a laminar loss of staining for tubulin. Evolution of the ischemic lesions in the thalamus and caudoputamen was delayed. However, in two hours widespread ischemic lesions were seen there. Evolution of the ischemic lesions was slightly slower with the reaction for creatine kinase BB-isoenzyme as compared to the reaction for tubulin, but was far more sensitive than hematoxylin-eosin staining. The distribution of ischemic lesions detected by the immunohistochemical method compared to ischemic areas detected by an India ink perfusion study suggested that both the extent of regional ischemia and regional difference in tissue vulnerability were contributing factors for the emergence of early ischemic lesions. The mechanism for prompt disappearance of the immunohistochemical reaction for tubulin is not clear, but the present investigation demonstrates the usefulness of the immunohistochemical technique for detecting early ischemic lesions and provides a possible biochemical mechanism for cellular damage after ischemic insults. PMID- 2579211 TI - Advanced testicular cancer: treatment choices in the "land of plenty". PMID- 2579212 TI - Chemotherapy of extragonadal germ cell tumors. AB - Forty-nine patients with histologically proven germ cell tumors arising in extragonadal sites were retrospectively reviewed. Included in the review were an additional seven patients with undifferentiated tumors with a pathologic appearance compatible with that of a germ cell tumor and elevated levels of serum biomarkers (beta subunit of human chorionic gonadotropin [beta-HCG] +/- alpha fetoprotein [AFP]. Nineteen patients had a pure seminoma arising in an extragonadal site, whereas 30 patients had nonseminomatous germ cell tumors. Seven patients had primary undifferentiated tumors with elevated levels of serum biomarkers. Sixteen (84%) of the 19 patients with pure extragonadal seminomas with normal levels of serum AFP are alive and free of disease. Eighteen of these 19 patients received platinum-containing regimens and four had received prior chemotherapy that failed. Of the patients with nonseminomatous germ cell tumors, 12 (40%) of the 30 are alive and free of disease with vinblastine/bleomycin +/- cisplatin (13 patients) or CISCAII (cisplatin, cyclophosphamide, and doxorubicin) (nine patients) alternating CISCAII/VBIV (eight patients) chemotherapy. None of the seven patients with undifferentiated germ cell tumors are alive and free of disease. Three of the five patients with pure anterior mediastinal endodermal sinus tumors treated with chemotherapy remain alive and free of disease. Of the seven patients with choriocarcinomas arising in extragonadal sites, three are alive and free of disease. A classification for patients with extragonadal germ cell tumors incorporating site of origin, histology, and likelihood of being truly extragonadal is proposed. The implications of this classification are discussed. PMID- 2579213 TI - Improved survival with cyclic chemotherapy for nonseminomatous germ cell tumors of the testis. AB - Forty-eight patients with advanced nonseminomatous germ cell tumors of the testis received a combination of cyclophosphamide, doxorubicin, and cisplatin (CISCAII) and a modified combination of vinblastine and bleomycin (VBIV) cyclic chemotherapy. Forty-four (92%) have achieved a complete remission. No patient in complete remission has relapsed with a mean follow-up of 139.0 weeks (SEM 7.0 weeks). The patients were stratified according to the modified Samuels clinical staging criteria. Thirty-seven (77%) had advanced disease (stage III-B3 to III B5), ten of whom had advanced visceral non-lung disease (stage III-B5). Chemotherapy was individualized by tumor volume and response to therapy. Two courses were delivered after complete remission or the development of a stable mass with negative serum biomarkers. Twenty-four patients (50%) were explored for a persistent and stable mass. No viable cancer was found; 15 (62%) had mature teratomas and nine (38%) had scar. No patients suffered from doxorubicin cardiotoxicity, clinical pulmonary bleomycin toxicity, or persistent cisplatin renal failure. Four patients died. One patient, an unrecognized drug abuser, died of toxicity. Three with far-advanced tumors died of progressive disease. CISCAII/VBIV cyclic chemotherapy is superior to chemotherapy with vinblastine, bleomycin, and cisplatin, resulting in a 92% complete remission rate and a significant reduction in long-term toxicity. PMID- 2579214 TI - VAB-6 as initial treatment of patients with advanced seminoma. AB - Thirty patients with advanced seminoma were treated with VAB-6. Eighteen patients were previously untreated, eight had relapsed after radiation therapy, and four had persistent disease following chemotherapy and radiation therapy. Two patients had received prior high-dose cisplatin. Twenty-four (86%) of 28 evaluable patients achieved a complete remission. Four patients had relapsed. The median disease-free follow-up of patients achieving complete remission was 32+ months. VAB-6 is effective treatment for patients with advanced seminoma, and chemotherapy is recommended as the initial therapy in all patients with stage II seminoma with disease larger than 5 cm, extragonadal seminoma, and stage III seminoma. PMID- 2579215 TI - Properties of persistent sodium conductance and calcium conductance of layer V neurons from cat sensorimotor cortex in vitro. AB - Properties of the persistent sodium conductance and the calcium conductance of layer V neurons from cat sensorimotor cortex were examined in an in vitro slice preparation by use of a single microelectrode, somatic voltage clamp, current clamp, intra- and extracellular application of blocking agents, and extracellular ion substitution. The persistent sodium current (INaP) attained its steady level within 2-4 ms of a step change in voltage at every potential where it could be examined directly [to about 40 mV positive to resting potential (RP)]. Because of its fast onset INaP can be activated during a single excitatory postsynaptic potential (EPSP) and can influence the subsequent voltage time course and cell excitability. Application of a depolarizing holding potential greater than or equal to 20 mV positive to RP could inactivate spikes, thus allowing examination of INaP at voltages positive to spike threshold. At every potential where INaP was visible, it was mixed with a slow outward current. After depressing potassium currents with blocking agents, INaP could be observed during depolarizations to about 40 mV positive to RP where it is normally hidden by the larger outward currents. Indirect evidence suggests that INaP is present and large during prolonged depolarizations greater than 50 mV positive to RP. INaP was blocked by intracellular injection of the lidocaine derivative QX-314, as well as by extracellular tetrodotoxin (TTX). INaP was much more sensitive to QX-314 than was the height and rate of rise of the spike. This observation and the results in paragraph 3 above are best explained by separate INaP and spike sodium channels. After blockade of INaP and sodium spikes, Ca2+ spikes could be evoked only if potassium currents were first depressed. The Ca2+-dependent nature of the regenerative potentials was indicated by their disappearance when Co2+ or Mn2+ was substituted for Ca2+ in the perfusate and by the appearance of greatly enhanced potentials of similar form when Ba2+ was substituted for Ca2+. Ba2+ substitution greatly enhanced evoked and spontaneous synaptic potentials. Prolonged-plateau action potentials could be evoked in the presence of TTX and Ba2+. Ca2+ spike threshold was 30-40 mV positive to RP, which is significantly more positive than sodium spike threshold. Results of voltage clamp in the normal perfusate and in the presence of Ca2+-blockers or Ba2+ indicated that little or no Ca2+ conductance is activated in the voltage range 25 mV positive to RP where INaP is the dominant ionic current.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2579216 TI - Calcium spike and calcium-dependent potassium conductance in mechanosensory neurons of the lamprey. AB - Action potentials (APs) of long duration (up to 1 s) followed by prolonged (0.5-5 s) hyperpolarizing afterpotentials (HAP) were recorded in lamprey primary mechanosensory neurons (dorsal cells) in isolated spinal cords exposed to either or both of the potassium channel blockers, tetrathylammonium (TEA) and 3,4 diaminopyridine (DAP). The membrane events underlying the prolonged AP and HAP were investigated in current clamp studies and were shown to be a Ca spike- and a Ca-dependent K conductance, respectively. The prolonged AP was accompanied by an increased membrane conductance and, unlike the normal Na AP in these cells, was not blocked by tetrodotoxin (TTX) or by replacement of external Na with choline or TEA. Reduction of [Ca]o from 10 to 0 mM reduced the amplitude and duration of the prolonged TTX-resistant AP but did not eliminate it within the 15-min washout period, probably because of Ca buffering in the spinal cord. The overshoot of the prolonged AP varied in amplitude as a linear function of the log of the external Ca concentration (2.5-10 mM) with a slope of 31.5 mV for a 10-fold change in Ca concentration, a value close to the 28 mV expected from the Nernst relation. Co (2 mM) and Cd (1 mM) blocked the prolonged APs. Ba and Sr substituted for Ca. The APs in Ba were extremely long lasting (up to 40 s). The HAPs following Ca spikes were 0.5-5 s in duration (peak to half amplitude) and were accompanied by an increased membrane conductance. The HAP varied in amplitude with the extracellular K concentration, reversed in sign at the presumed K equilibrium potential (-90 mV), and was insensitive to injected Cl. We conclude that HAP is a result of increased K conductance. The increase in K conductance during the HAP appeared to be dependent on Ca influx, because the amplitude and duration of the HAP varied with the extracellular Ca concentration and increased in duration during repetitive Ca spike activation, presumably as a result of accumulation of Ca intracellularly. Further, the HAP was absent following even very long lasting spikes in Ba, an ion that in other cells does not activate the Ca-dependent K conductance. Small regenerative depolarizations sometimes followed Ca spikes in dorsal cell somata. These are believed to reflect Ca spikes in discrete axonal regions at various electrotonic distances from the soma. PMID- 2579217 TI - A panel of monoclonal antibodies to the rat olfactory epithelium. AB - BALB/c mice were immunized with dissected olfactory mucosa from young adult Sprague-Dawley-derived, CD, rats and antibody-secreting hybridomas were produced. Supernatants from hybridoma cultures were screened by immunocytochemical methods for their ability to react with specific cell populations in frozen sections of rat olfactory epithelium. Approximately 60 clones were identified that showed various degrees of specific staining. These have been classified on the basis of their particular staining specificities. One group of monoclonal antibodies, designated LUM, reacts with the luminal surface of the epithelium. Closer examination reveals these antibodies to react variously with the apical brush border of sustentacular cells, respiratory cilia, and the luminal membrane of respiratory cells. Another group of monoclonal antibodies reacts primarily with sustentacular cells, as is indicated by the SUS prefix. Some antibodies in this group also react with the membranes of respiratory cells and the cells comprising the acini of Bowman's glands. A larger group of antibodies reacts with olfactory neurons and/or their axons, as denoted by the NEU prefix. This group can be further subdivided by the criteria of whether both the olfactory nerve and vomeronasal nerve react with the same monoclonal antibody. A fourth group of monoclonal antibodies, designated GLA, reacts with Bowman's glands and in some instances with secretory cells present in the respiratory mucosa. Two clones, BCL, stain at the level of the basal cell layer just above the lamina propria. A number of other antibodies react with cells and structures of the epithelium that have not been previously described. One of this group, NIS-1, stains globular structures present in the mucosa of the neuroepithelium. PMID- 2579218 TI - Concentration-dependent effects of neostigmine on the endplate acetylcholine receptor channel complex. AB - The concentration-dependent actions of neostigmine, a carbamate anticholinesterase agent, were studied on the acetylcholine receptor channel complex in voltage-clamped twitch fibers of costocutaneous muscles of garter snakes. Low concentrations of neostigmine (10(-6) or 10(-5) M) increased miniature endplate current (MEPC) amplitude and the time constant of MEPC decay without changing the relationship between the MEPC decay time constant and membrane potential. Acetylcholine- or carbachol-induced endplate current fluctuation spectra were well fitted by a single Lorentzian curve with a characteristic frequency and single-channel conductance unaltered by low concentrations of neostigmine. Concentrations of neostigmine greater than 5 X 10( 5) M decreased MEPC amplitude and split the decay of MEPCs into two components, one faster and one slower than the control rate. These effects were both voltage and concentration dependent. Spectra of current fluctuations recorded in concentrations greater than or equal to 5 X 10(-5) M neostigmine required two time constants, one faster and one slower than the control. Two component spectra were also obtained with carbachol-induced current fluctuation spectra, indicating that these effects of neostigmine were direct and not a consequence of acetylcholinesterase inhibition. Similar results were also obtained in muscles pretreated with collagenase to remove junctional acetylcholinesterase. The fast and slow time constants obtained from current fluctuation spectra decreased and increased, respectively, with either increases in the concentration of neostigmine or membrane hyperpolarization when analyzed in the same fiber. The effects of neostigmine on channel lifetime were reversible with washing. These results indicate that the effects of neostigmine are concentration dependent. Concentrations greater than 2.5 X 10(-5) M exhibit direct effects on the endplate receptor channel complex which are unrelated to acetylcholinesterase inhibition. These actions include: a prolongation of the gating kinetics of the endplate receptor channel complex, the production of an altered state of the receptor channel complex evidenced by a high frequency component to current fluctuation spectra, and a direct action to block the acetylcholine receptor. PMID- 2579219 TI - A regional analysis of alpha-spectrin in the isolated Mauthner neuron and in isolated axons of the goldfish and rabbit. AB - Isolated dendrites, somata, and desheathed axons of the goldfish Mauthner neuron (M-cell), in addition to other isolated myelin sheath-free axons of the goldfish spinal cord and of rabbit lumbar ventral roots, were shown by immunochemical and immunofluorescence techniques to contain alpha-spectrin (fodrin). alpha-Spectrin appeared to be organized as a randomly distributed reticular network, localized to the surface of isolated neuronal cellular structures. In addition, alpha spectrin was also distributed nonrandomly at specialized cellular sites. These sites included synaptic junctions and morphologically differentiated nodes of Ranvier (i.e., rabbit axons, but not goldfish axons). At the latter sites, it is possible to demonstrate that alpha-spectrin is co-localized with F-actin, as indicated by a striking correspondence of fluorescent images due to double labeling, using the indirect immunofluorescence technique with alpha-spectrin antiserum, and direct binding of F-actin by rhodamine-conjugated palloidin. However, the spectrin-actin network at synaptic junctions appears to be distributed over the entire area of junctional contact and is not just restricted to postsynaptic densities. The possibility of a duality of roles of spectrin in membrane-related motile and anchorage functions is discussed. PMID- 2579222 TI - Alterations in mentation: nursing assessment and intervention. AB - Physical assessment for nursing purposes is necessarily different from that of medicine because the focus of nursing is to diagnose and treat human responses to disease rather than the disease itself. Nursing assessment pathophysiology, implications for daily living, and nursing interventions for selected functional aspects of mentation, namely language, remembering, and performing learned movements, are presented in this article. PMID- 2579221 TI - Arteriovenous malformations: complications of surgical intervention and implications for nursing. AB - Arteriovenous malformations occur in approximately 4 percent of the population and are frequently seen in young adulthood. Controversy exists in the neurosurgical community as to the management of arteriovenous malformations; the four most common methods are medical management, radiation, embolization, and surgical intervention. Complications occur frequently regardless of the treatment selected. These complications are discussed using a selected patient population and case studies. Nursing diagnosis is used and a plan of care formulated for each problem. A one-year follow-up status will also be given for the selected patient population. PMID- 2579220 TI - Calcium channels in rat brain synaptosomes: identification and pharmacological characterization. High affinity blockade by organic Ca2+ channel blockers. AB - Rat brain synaptosomes are shown to contain functional voltage-sensitive Ca2+ channels that are inhibited by organic Ca2+ channel blockers. Depolarization of synaptosomes with high K+ stimulates uptake of 45Ca2+ which is biphasic in its time course. Replacement of external Na+ with choline eliminates the slower phase of depolarization-stimulated Ca2+ uptake, leaving only a rapid uptake process which terminates within 1 sec. This rapid, tetrodotoxin-insensitive Ca2+ uptake can be inactivated by prior depolarization of the synaptosomes. Depolarization has no effect on the rate of synatptosomal 22Na+ efflux. These results are interpreted as ruling out Na+/Ca2+ exchange as a mediator of the rapid phase of depolarization-stimulated Ca2+ uptake. A portion (30 to 50%) of the rapid phase of depolarization-stimulated Ca2+ uptake is inhibited by nitrendipine, as is depolarization-stimulated [3H]norepinephrine release from synaptosomes. In external Na+, the inhibition constant (Kapp) for nitrendipine inhibition of Ca2+ uptake is 56 nM. The potency of nitrendipine is increased in the absence of external Na+ (Kapp = 1.7 nM), such that inhibition correlates more closely with the equilibrium dissociation constant for [3H] nitrendipine binding to synaptosomes (Kd = 0.35 nM). Other organic channel blockers (nifedipine, verapamil, D600, and dilitiazem) inhibit the rapid Ca2+ uptake. The potencies of all Ca2+ channel blockers tested by us are in reasonable agreement with their potencies, observed in other laboratories, as blockers of Ca2+ channels in smooth and cardiac muscle. These data demonstrate the existence of active voltage sensitive Ca2+ channels in synaptosomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579223 TI - Odontogenic keratocysts: review of the literature and report of sixteen cases. AB - Sixteen cases of odontogenic keratocyst are reported. Two of the patients had basal cell nevus syndrome. The provisional diagnosis in most of the 16 cases was other than odontogenic keratocyst, and the presenting symptoms were usually swelling, pain, and sinus tract formation. The treatment varied from simple enucleation to marsupialization, homogenous bone grafting, and iliac bone grafting. There was a 25% recurrence rate, mostly associated with treatment by enucleation, cysts that were parakeratinized or difficulty in removing the lesion. PMID- 2579224 TI - The effects of immobilization on the rabbit temporomandibular joint. AB - While the effects of immobilization of joints covered with hyaline cartilage have been widely studied, the effects on the fibrous tissue-covered temporomandibular joint have not been studied as extensively. This study was designed to determine the short-term effects of immobilization on the rabbit temporomandibular joint. Nineteen rabbits were placed in maxillomandibular fixation. The temporomandibular joints were studied histologically after periods of from ten to 28 days. Significant thinning was observed as early as after ten days, as was degeneration of the cartilage. Degeneration became progressively more severe as the duration of the immobilization increased. Reparative events began appearing after 28 days. These findings suggest that although initially immobilization produces destructive changes, the changes may well be reversible. PMID- 2579225 TI - Immunohistochemical analysis of human MHC class II antigens in B-cell non Hodgkin's lymphomas. AB - Twenty cases of B-cell non-Hodgkin's lymphoma (NHL) were evaluated by immunohistochemical staining of frozen sections with a panel of anti MHC class II monoclonal antibodies (MCA). These studies showed marked differences in the expression of class II antigens both between different cases and within the population of cells of individual cases. In all of the cases studied the majority of the tumour cells reacted with MCAs directed against determinants common to the products of SB and DR loci. However, MCAs specific for DC determinants failed to react with 3/20 cases and in several other cases stained only a minority of cells. Absent or reduced expression of DC antigens was most marked in lymphocytic lymphoma; however, in centroblastic-centrocytic and centroblastic lymphomas, DC antigens could be detected on the majority of cells. PMID- 2579226 TI - Buffy coat smears of blood drawn through central venous catheters as an aid to rapid diagnosis of systemic fungal infections. PMID- 2579227 TI - Splenic function in sickle cell disease. PMID- 2579228 TI - Cholangio-venous reflux as a cause of recurrent hyperamylasemia in choledochal dilatation with anomalous pancreaticobiliary ductal union: an experimental study. AB - Cylindrical choledochal dilatation, associated with anomalous pancreaticobiliary ductal union, causes recurrent episodes of right hypochondrial pain, vomiting, and fever. The symptoms are very often accompanied by hyperamylasemia, which is generally considered to be due to acute pancreatitis. However, our clinical experience and experimental studies have led us to the conclusion that pancreatitis is not the sole cause of hyperamylasemia. In this paper we report our further investigations of the cause of the hyperamylasemia. In 22 mongrel adult dogs, intracholedochal infusion was performed under a continuous hydrostatic pressure of 20 cm H2O for 2 hours. Solutions of amylase from three different sources and a lipase were used in the range of concentrations found clinically in the bile within a cylindrical choledochal dilatation. In the 3 groups, hyperamylasemia was proven by quantitative estimation of serum amylase level and/or by the changes in specific amylase isozymes. Lipase was also shown to transfer into the blood stream. In an additional experiment on 5 dogs, only the extrahepatic biliary tree, including the gallbladder, was infused with a solution of amylase from Bacillus subtilis. This produced no increase in the serum amylase. Our experiments suggest that amylase passes from the hepatocholedochal system into the blood stream. This phenomenon has long been known as cholangiovenous reflux. PMID- 2579229 TI - Analysis of lymphocyte populations extracted from chronically inflamed human periodontal tissues. I. Identification. PMID- 2579230 TI - Pirenzepine distinguishes between muscarinic receptor-mediated phosphoinositide breakdown and inhibition of adenylate cyclase. AB - Subtypes of muscarinic cholinergic receptors have been proposed to exist, but the biochemical responses mediated by the putative subtypes are unknown. In the present study, muscarinic receptor-mediated phosphoinositide breakdown and inhibition of adenylate cyclase activity were characterized in rat brain as well as rat parotid and heart. To study whether these responses are mediated by separate subtypes of muscarinic receptors, the potencies of agonists and antagonists were determined in both assays. Antagonist potencies were calculated by Schild analysis. In the brain, the putatively selective muscarinic receptor antagonist, pirenzepine, exhibited Ki values of 21 nM in the assay of phosphoinositide breakdown and 310 nM in the assay of adenylate cyclase activity. Similarly, using radioligand binding techniques, it distinguished two binding sites with Kd values of 12 and 168 nM. The antagonist, atropine, on the other hand, was equipotent in the two biochemical assays and the radioligand binding assay with Ki values of approximately 1 to 2 nM. In peripheral tissues with robust muscarinic receptor-mediated phosphoinositide (parotid) and adenylate cyclase (heart) responses, pirenzepine exhibited a similar selectivity (19-fold) for the phosphoinositide assay that was seen in the brain, but it was 6- to 7 fold less potent in both peripheral tissues than in the central nervous system. In addition, the potencies of pirenzepine in binding and functional studies in each tissue were not as well correlated as in the brain. Atropine and other antagonists were 4- to 9-fold selective for inhibiting oxotremorine-stimulated phosphoinositide breakdown in the peripheral tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579232 TI - Cobalt-sensitive biphasic uptake of calcium ions in potassium-depolarized smooth muscle. AB - Isolated longitudinal muscle from guinea-pig ileum was immersed in a calcium depleted, high-potassium medium for 10 min and then induced to contract by adding 1.8 mM CaCl2. It exhibited a biphasic response that consisted of an initial, rapid, transitory contraction--the phasic response--followed by a slower more sustained contraction--the tonic response. 45Ca uptake was also measured. Only that fraction of the accumulated calcium that could be inhibited by cobalt ion was considered to be intracellular calcium. The data showed that the phasic contraction was accompanied by a brief, rapid uptake of calcium ions and the tonic response was accompanied by a slower, more prolonged uptake of calcium ions. When the muscle, after undergoing an initial biphasic contraction, was reincubated in the calcium-depleted, high-potassium medium for 70 to 80 min, the phasic contraction that it exhibited upon the readdition of 1.8 mM CaCl2 remained unaltered, but the tonic contraction was delayed and substantially diminished. Under these conditions, the rate of the initial brief, rapid uptake of calcium was reduced by 20%, whereas the subsequent slow, prolonged uptake of calcium was measurably delayed and its rate was reduced by an average of 31.4%. Calcium pulse experiments showed that variations in the rate of calcium uptake were due primarily to variations in the rate of the inward movement of calcium ions. The results suggest that the biphasic mechanical response is a reflection of a biphasic influx of calcium ions in the potassium-depolarized longitudinal muscle. PMID- 2579231 TI - Metabolic activation of phosphorothioate pesticides: role of the liver. AB - Mouse liver perfusion studies in situ revealed that the cholinesterase inhibitor chlorpyrifos oxon produced by the liver from the phosphorothioate pesticide chlorpyrifos was quickly detoxified within the liver, thereby preventing it's exit from the liver in the effluent. In contrast, when the pesticide parathion was perfused as a substrate a substantial amount of the toxic metabolite paraoxon was found in exiting perfusate. Pesticide concentrations (5-15 microM) used in the perfusion studies in situ were similar to their hepatic portal blood concentrations in vivo (2.32-12.95 microM) after i.p. administration of lethal or near lethal doses. Moreover, the half-life for elimination of paraoxon by mouse blood in vitro was 8.6 min, a rate sufficiently low to allow passage of paraoxon to extrahepatic target tissues from liver in vivo. These results suggest that in the mouse, the acute toxicity of chlorpyrifos is mediated by extrahepatic production of oxon, whereas that of parathion is likely mediated by both hepatic and extrahepatic activation. PMID- 2579233 TI - Effects of substance P on cholinergically stimulated gastric acid secretion and mucosal blood flow in rats. AB - Effects of substance P (SP) on gastric acid secretion and mucosal blood flow (MBF) were examined in anesthetized Wistar rats. Intravenous infusion of graded doses of SP (5 and 10 nmol/kg/min) had no effects on either the basal gastric acid secretion or on the MBF. When gastric acid secretion was increased by giving a supramaximal dose of bethanechol (10 micrograms/kg/min), a muscarinic parasympathetic stimulant, SP had no effect on the gastric acid secretion but did decrease the MBF. On the other hand, when gastric acid secretion was increased by left cervical vagus nerve stimulation (0.5 mA, 3 Hz, 0.5 msec duration), SP inhibited both acid secretion and MBF, in a dose-dependent manner. The inhibitory effects of SP on the vagally stimulated gastric responses were not affected by pretreatment with phentolamine (5 mg/kg i.m.), propranolol (10 mg/kg i.m.), mepyramine (20 mg/kg i.m.) or indomethacin (30 mg/kg i.v., followed by 4 mg/kg/hr). These findings suggest that SP acts directly on the gastric vascular system and decreases gastric MBF, and that this substance also acts on the parasympathetic neurons in the gastric wall and inhibits the vagally stimulated gastric acid secretion. The inhibitory effects of SP on the gastric acid secretion do not appear to be mediated by adrenergic or by histamine H-1 receptor , prostaglandin-involved mechanisms. PMID- 2579234 TI - Variability of heparin levels and bleeding with low-dose heparin prophylaxis following transurethral resection of the prostate. AB - Plasma heparin levels and operative/postoperative bleeding were assessed in 16 patients of varying body weights who received subcutaneous low-dose heparin prophylaxis for deep vein thrombosis during and after transurethral resection for benign prostatic hypertrophy. The concentration of heparin in the blood at operation and subsequently was found to vary widely but did not correlate with the extent of blood loss. When adjusted for body weight, plasma heparin concentration showed significantly less variation from patient to patient. In this respect, body weight was a more effective parameter than lean body mass or surface area. Adjustment of heparin dosage by body weight may be advisable when using low-dose heparin prophylaxis. PMID- 2579235 TI - Algodystrophy (Sudeck's syndrome) in association with hereditary angioneurotic oedema. PMID- 2579236 TI - 1,2,4-Triazolo[4,3-a]quinoxaline-1,4-diones as antiallergic agents. AB - A series of new 1,4-dihydro-1,2,4-triazolo[4,3-]quinoxaline-1,4-diones has been prepared. These compounds were tested as inhibitors of antigen-induced release of histamine (AIR) in vitro from rat peritoneal mast cells (RMC) and as inhibitors of IgE-mediated rat passive cutaneous anaphylaxis (PCA). Most of this new class of antiallergic agents showed good activity in the RMC and PCA tests. The most potent compound, 2-acetyl-7-chloro-5-n-propyl-1,2,4-triazolo[4,3-a]quinoxaline 1,4-dione (1x), with an I50 value of 0.1 microM, is 30 times more potent than disodium cromoglycate (DSCG) in the RMC assay. PMID- 2579237 TI - [3H]Batrachotoxinin A 20 alpha-benzoate binding to voltage-sensitive sodium channels: a rapid and quantitative assay for local anesthetic activity in a variety of drugs. AB - [3H]Batrachotoxinin A benzoate ( [3H]BTX-B) binds with high affinity to sites on voltage-dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex. In this preparation, local anesthetics competitively antagonize the binding of [3H]BTX-B. The potencies of some 40 classical local anesthetics and a variety of catecholamine, histamine, serotonin, adenosine, GABA, glycine, acetylcholine, and calcium antagonists, tranquilizers, antidepressants, barbiturates, anticonvulsants, steroids, vasodilators, antiinflammatories, anticoagulants, analgesics, and other agents have been determined. An excellent correlation with the known local anesthetic activity of many of these agents indicate that antagonism of binding of [3H]BTX-B binding provides a rapid, quantitative, and facile method for the screening and investigation of local anesthetic activity. PMID- 2579238 TI - The pKa of butaclamol and the mode of butaclamol binding to central dopamine receptors. AB - The pKa values for butaclamol (1), 1,2,3,5,6,10b beta-hexahydro-6 alpha phenylpyrrolo[2,1-alpha]isoquinoline (2, McN-4612-Y), and 2-tert-butyl 1,3,4,6,7,11b beta-hexahydro-7 beta-phenyl-2H-benzo[alpha]quinolizin-2 alpha-ol (3, McN-4171) were determined to be 7.2, 9.1, and 7.0, respectively. The values for 1 and 3 are anomalous; however, the value for 1 (7.2) is not as low as the one reported in the literature (pKa = 5.9). We also determined pKa values for apomorphine, chlorpromazine, and lidocaine, for reference purposes (7.6, 9.2, and 7.9, respectively). The results indicate that 1 would not be predominantly unprotonated under the physiological conditions of receptor binding, rather it would be about 50% protonated. This fact may contravene a suggested binding model used to map the central dopamine receptor (viz., ref 3). PMID- 2579239 TI - A new method for obtaining scanning electron microscopic images of the reorganization process of human dermal microvascular endothelium in vitro. AB - A new method for obtaining scanning electron microscopic images of the reorganization process of endothelial cells has been developed. When covered with a collagen-coated disk, all the cultured endothelial cells reorganized on the collagen of the disk, which was easily taken out from the dish to process for SEM. The reorganization process could be divided into four stages: endothelial cell growth (Stage 1), reticular network formation (Stage 2), tubular structure formation (Stage 3), and cytolysis of the tube (Stage 4). Between Stages 1 and 2 the endothelial cells transformed from a cobblestone to a spindle-shaped pattern and fused each other, forming a board-like structure. Between Stages 2 and 3 break up of parts of the board-like structure and outflow of a necrotic mass from the centre of the structure occur. At Stage 3 a tubular structure is formed following enwrapping of the cleared centre by the surrounding endothelial cells. This method produces a means to study the angiogenesis in a variety of disorders including tumours and wound-healing process using SEM. PMID- 2579240 TI - Steady growth cone currents revealed by a novel circularly vibrating probe: a possible mechanism underlying neurite growth. AB - The rate and direction of neurite growth have been shown in a number of studies to be determined by the distribution of adhesive sites on the growth cone. Recent evidence showing that the application of extrinsic electric fields can redistribute membrane molecules and alter both the rate and direction of neurite growth have raised the question whether endogenous electric fields might be produced by steady currents in growth cones. To investigate this question, we have devised a novel circularly vibrating microprobe capable of measuring current densities in the range of 5 nA/cm2 (near the theorectical limit of sensitivity), with a spatial resolution of 2 micron. The design of this device and the development of a novel algorithm for computing current vectors on-line is described. Using this probe we have found that cultured goldfish retinal ganglion cell growth cones generate steady inward currents at their tips. The measured currents, in the range of 10-100 nA/cm2, appear to flow into the filopodia at their tips and back outward near the junctures of the filopodia and the growth cone. The currents appear to be produced only during active growth. Ion substitution experiments support the conclusion that the majority of this current is carried by Ca2+ ions, which we postulate flow through a population of activated voltage-sensitive Ca2+ channels located on the filopodial tips. Calculation of the transmembrane current density (4 X 10(-6) nA/cm2) leads to an estimate of channel density (10 channels/micron2) in close agreement with the measured density of Ca2+ channels in other systems. The assumption that calcium channel proteins are conveyed to nerve terminals by active transport, whereas sodium channel proteins are conveyed passively by a slower somatofugal diffusion process [Strichartz et al, 1984], would explain why developing neurons tend to display Ca2+-sensitive electrogenesis at their growing tips, and Na+-sensitive action potentials later in development. In order to gain some insight into the possible role of these steady growth currents, we estimated the membrane depolarization and axial voltage gradient they produce. It is likely that the currents produce sufficient membrane depolarization (approximately equal to 4 mV) to cause autogenous activation of ion channel permeabilities. Similarly, the axial voltage gradient (approximately equal to 4 mV/cm) would be expected to move intracytoplasmic vesicles by electrophoresis at a rate (20-40 microns/hr) very close to that at which the filopodia are observed to grow.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2579241 TI - Single channel activity differs in growing and nongrowing growth cones of isolated identified neurons of Helisoma. AB - When plated in cell culture, Helisoma neurons extend new neurites with large growth cones. These growth cones progress from actively growing organelles to stable structures over a period of several days. The ability to distinguish morphologically between these growth states has provided the opportunity to test whether changes in growth status are correlated with changes in the ionic properties of the growth cone membrane. This investigation has begun to study these changes by examining single channel ionic currents using patch clamp recording techniques and has demonstrated the presence of at least one ion channel having a conductance of 70 pS in the membrane of Helisoma growth cones. Recordings from cell-attached patches show that this channel is normally active in growing growth cones, whereas channel activity is absent in recordings from stable growth cones. The absence of channel activity in growth cones that have reached the stable state is not due to the loss of channels from these growth cones. Rather, the channel is present in an inactivated state. The activity of this channel is not dependent on the presence of Ca, as channel activity persists when Ca is removed from the solution that bathes the internal surface of the membrane. These data demonstrate a correlation between channel activity and the growth state of neuronal growth cones. PMID- 2579242 TI - Morphological properties and membrane channels of the growth cones induced in PC12 cells by nerve growth factor. AB - Large growth cones were produced in vitro by nerve growth factor (NGF) treatment of multinucleate cells produced by chemical fusion of cells of the neuron-like clone PC12. These endings were studied both at the light microscopic and ultrastructural levels. The activity of ionic channels at growth cones was recorded with intracellular microelectrodes, patch recording of single channels, and whole cone recording from mechanically isolated growth cones. Morphologically, these large growth cones were characterized by the presence of microspikes and filopodia, by the presence of actin demonstrated immunohistochemically, and by the presence of catecholamine fluorescence. At the ultrastructural level they contained a broad spectrum of organelles with a distribution characteristic of neuronal growth cones, including dense core vesicles, abundant smooth membrane cisternae, microtubules, and a filamentous network. The presence of channels capable of generating action potentials was revealed by intracellular microelectrode recording from the growth cone in the presence of locally applied tetraethylammonium (TEA). TEA appeared to block outward current channels that could effectively shunt inward current activated by depolarization. Action potentials elicited by depolarizing current in the presence of TEA could be blocked reversibly by Cd2+, a specific blocker of Ca channels. These action potentials were often followed by a long after hyperpolarization lasting hundreds of milliseconds. This after-hyperpolarization was similar to that recorded in the cell body of PC12 cells where it appears to be mediated by Ca-activated K current. Single channel recording from outside-out excised patches of membrane from the growth cones perfused with KF revealed the presence of voltage sensitive Na channels, Ca-activated K channels, and K channels resembling delayed rectifier K channels. Macroscopic currents recorded from mechanically isolated growth cones in the "whole cone" configuration showed rapid inward currents at potentials greater than or equal to -40 mV, followed by delayed outward currents at more positive potentials, a finding providing additional evidence for the presence of Na and K channels in growth cones. PMID- 2579243 TI - Barium action potentials in regenerating axons of the lamprey spinal cord. AB - Intracellular recordings were obtained from growing tips of regenerating giant axons in the lamprey spinal cord, the recording sites verified by Lucifer yellow injection. In the presence of extracellular Ba++ (3-6 mM), tetraethylammonium (10 15 mM), and 4-aminopyridine (4-6 mM), action potentials showed prolonged plateaus. The fast initial phase of the action potential, but not the plateau (Ba++-spike), was blocked by tetrodotoxin (10(-6) gm/ml). The Ba++ spike was associated with increased membrane conductance and could be terminated with hyperpolarizing current pulses. Normal axons did not generate similar Ba++ spikes. However, TTX-resistant, voltage-dependant conductance changes could be elicited in normal axons if much higher concentrations of Ba++ (18-30 mM) were used. Their rate of rise was slower than in regenerating axons (0.6 V/sec vs 3.2 V/sec; n = 5), and the response did not outlast the current pulse. The Ba++ responses in normal and regenerating axons were blocked by ions known to block voltage-gated Ca++ conductances (Co++, Ni++, or Cd++). Therefore, these spikes probably represent Ba++ entry through voltage-dependent Ca++ channels, suggesting the presence of a higher-than-average voltage-dependent Ca++ conductance in the growing axon. However, Ca++-dependent spikes could not be obtained under any conditions in either normal or regenerating axons. Simultaneous intracellular recordings from growth cones and axons indicated that the Ba++ spike was initiated, in most cases, at the growth cone. The Ba++ spikes were recorded in regenerating axons for as long as 50 days following cord transection and were not correlatable with the "dying-back" phenomenon in cut axons, which usually is over before day 6. The concept of a higher-than-average voltage-dependent Ca++ conductance in growing tips of regenerating axons is in agreement with the hypothesis that Ca++ is important in regeneration and that regeneration may be related to the process of chemical synaptic transmission. PMID- 2579244 TI - Transrectal prostatic ultrasonography: comparison of linear array and radial scanners. AB - Transrectal ultrasound probes can image the prostate only in a single plane. A retrospective study was undertaken to evaluate the capabilities and differences of longitudinal and transversely oriented images obtained from transrectal sonographic examinations. The patients were studied by both modalities using commercially available machines. Comparisons of the images demonstrated that the transverse image yielded more information about the lateral margins of the prostate; the longitudinal image showed the apex and base more clearly; prostatic calculi, which can be confused with other pathologic processes, were more accurately identified by the longitudinal scanners; and both techniques adequately demonstrated the abnormality, particularly cancer, although some lesions were seen better on either one or the other orientation. Either scanner can be used for a satisfactory study, but both methods may have to be utilized to conduct a thorough evaluation of the prostate and surrounding structures. PMID- 2579245 TI - Immunological responsiveness against tumors induced by avian sarcoma virus: reduced expression of pp60src kinase activity in regressing tumors. AB - Tumors which are induced in chickens by avian sarcoma virus frequently grow progressively for several weeks and then regress. We showed that tumor cells which are derived from the progressively growing phase of tumor growth produce large quantities of progeny-transforming virus, are reactive with antiviral antibody, and are susceptible to lysis in cell-mediated cytotoxicity assays by splenic lymphocytes of sensitized hosts. In contrast, tumor cells derived from regressing sarcomas are poor producers of progeny virus and are relatively unreactive with both antiviral antibody and sensitized lymphocytes. We further found that pp60src kinase activity was reduced by about 75% in regressing compared with progressively growing tumor cells. The half-lives of directly precipitable pp60src in tumor cells derived from progressively growing and regressing neoplasms were 6 and 1.5 h, respectively. Studies on each of three other cellular enzymes did not reveal any regression-associated decreases in enzyme activity. These data support the notion that expression of adequate levels of long-lived pp60src kinase activity is essential to progressive tumor growth. PMID- 2579247 TI - Rabies virulence: effect on pathogenicity and sequence characterization of rabies virus mutations affecting antigenic site III of the glycoprotein. AB - Using four neutralizing monoclonal antibodies which presumably bind to the same antigenic site on the CVS glycoprotein (antigenic site III as defined by cross neutralization tests), we isolated 58 mutants of the CVS strain of rabies virus. These mutants were highly resistant to the selecting antibodies and grew efficiently in cell cultures. We classified them into five groups on the basis of the pattern of resistance to the four antibodies. We determined pathogenicities of the mutants for adult mice by intracerebral inoculation. Group 2 mutants were nonpathogenic or had attenuated pathogenicity. On the contrary, mutants from the other groups were pathogenic, causing paralysis and death as does CVS. We determined the nucleotide alterations of representative mutants from each group by using the dideoxy method of RNA sequencing. In the glycoproteins of eight nonpathogenic or attenuated mutants, we identified an amino acid substitution at position 333. Arginine 333 was replaced by either glutamine or glycine. In the glycoprotein of eight pathogenic mutants, we identified an amino acid substitution at lysine 330, asparagine 336, or isoleucine 338. Thus, although all substitutions affected neutralization and were located close to each other in the glycoprotein sequence, only substitutions at position 333 affected pathogenicity. PMID- 2579246 TI - Altered processing of a major secreted phosphoprotein correlates with tumorigenicity in Rous sarcoma virus-transformed mammalian cells. AB - Anchorage-independent growth is highly correlated with neoplastic growth in vivo, and the retinoids (vitamin A and its analogs) inhibit this property in a wide variety of oncogenically transformed cells. We report here that retinoic acid treated Rous sarcoma virus-transformed rat (RR1022) and vole (SR-1T) cells, which show reversible loss of anchorage-independent growth and assume nontransformed morphology, secrete a major 69-kilodalton phosphoprotein (pp69) instead of the 62 kilodalton phosphoprotein (pp62) secreted by their untreated counterparts. As determined by V8 protease mapping and by two-dimensional electrophoretic analysis, this 69-kilodalton polypeptide was indistinguishable from the pp69 released by nontransformed normal rat kidney cells. Neither retinoic acid-treated RR1022 cells nor normal rat kidney cells secreted pp62, and retinoic acid treatment did not have any significant effect on the synthesis, subcellular localization, or phosphokinase activity of pp60src. Furthermore, treatment with retinoic acid did not alter the synthesis of the transformation-specific 53 kilodalton phosphoprotein (p53) and secretion of the transforming growth factors in RR1022 cells. Our studies showed that there is a clear correlation between the release of pp69 or pp62 and the ability of cells to grow in vitro with or without anchorage. This may provide an important clue for elucidating specific biochemical events involved in anchorage regulation of growth. PMID- 2579248 TI - Cloning and nucleotide sequences of cDNAs spanning the splice junctions of Rous sarcoma virus mRNAs. AB - The cDNAs corresponding to the 5' ends of the mRNAs coding for the envelope protein precursor (gPr92env) of the B77 strain and the transforming protein (pp60src) of the Prague B strain of Rous sarcoma virus were cloned into pBR322, and the nucleotide sequences surrounding the splice junctions were determined. Both mRNAs are products of single splicing events from a common donor splice site at nucleotide 398 from the 5' end of the RNA to acceptor splice sites at nucleotides 5078 and 7054 for the env and src mRNAs, respectively. These results confirm and extend previous conclusions based on peptide mapping and single strand nuclease mapping. Compared with the sequence of the Prague C genome RNA, the B77 strain contains a 6-nucleotide deletion in the sequence corresponding to the hydrophobic portion of the signal peptide of the envelope protein precursor. PMID- 2579249 TI - Neutralizing monoclonal antibodies to human rotavirus and indications of antigenic drift among strains from neonates. AB - Cells producing neutralizing monoclonal antibodies to a serotype 3 human neonatal rotavirus strain RV-3 were derived by fusion of hyperimmunized mouse spleen cells with mouse myeloma cells. As ascites fluid, three rotavirus-neutralizing monoclonal antibodies were characterized by hemagglutination inhibition and reacted with 17 cultivable mammalian rotaviruses representing five virus serotypes, by fluorescent focus neutralization and enzyme immunoassay. Two antibodies, Mab RV-3:1 and Mab RV-3:2, reacted with the seven serotype 3 rotaviruses only. Mab RV-3:1 was shown to bind to the outer capsid glycoprotein gp34 of rotavirus when variants of SA 11 rotavirus were used, and it therefore appears to react with the major neutralization epitope of serotype 3 rotaviruses. The antibody Mab RV-3:3 was specific for an epitope of RV-3 rotavirus not present on any other rotavirus of any serotype tested, including another neonatal isolate of identical RNA electropherotype isolated from the same ward of the same hospital as RV-3 3 months earlier. These two viruses were also distinguishable by fluorescent focus neutralization, using antiserum to RV-3 virus. Western blot analysis showed binding of Mab RV-3:3 to the trypsin cleavage product of the outer capsid protein p86 of RV-3. This suggests that antigenic drift may have occurred among neonatal rotaviruses in Melbourne. These monoclonal antibodies will be useful in serotyping assays of rotaviruses directly in stool samples, and in further analysis of antigenic variation within the serotype. PMID- 2579250 TI - Exfoliative cytology of prostatic carcinoma using a prostatic fluid collecting catheter. AB - In 152 patients who were suspected to have prostatic disease prostatic fluid obtained by a specially designed catheter was examined cytologically. Cytology was positive in 16 of 20 patients who initially were diagnosed clinically as having prostatic carcinoma, in 10 of 41 patients with suspected carcinoma and in 3 of 91 patients with clinical prostatic hypertrophy or other benign diseases. All but one of these cytologically positive cases finally were confirmed histologically to have prostatic carcinoma. In 4 patients initially diagnosed as having prostatic carcinoma cytology was not positive but in one the initial clinical diagnosis was incorrect and only 3 were false negative. This method of diagnosis is simple and highly effective in detecting prostatic carcinoma. PMID- 2579251 TI - Cost-effective uroflowmetry in men. AB - A simple method of timed urine flow measurement performed at home by the patient is compared to instrumental measurements of peak flow rate. The timed method correlates well with the peak flow rate. Timed uroflowmetry is free, can be done in the privacy of the home and provides multiple measurements. This is a valid technique to document a weak stream and is a useful screening test for patients with lower urinary tract obstruction. PMID- 2579252 TI - Comparison of the incidence of bladder hyperreflexia in patients with benign prostatic hypertrophy and age-matched female controls. AB - Detrusor hyperreflexia long has been recognized as a condition associated with certain neurological disorders (that is multiple sclerosis, cerebrovascular accidents, spinal cord injuries and parkinsonism). Bladder outlet obstruction (primarily benign prostatic hypertrophy) recently has been added to the list. Hyperreflexia associated with bladder outlet obstruction does not always resolve with relief of the obstruction. Our study of age-matched female controls indicates that there is a baseline rate of hyperreflexia associated with the aging process alone. This baseline hyperreflexia probably explains persistent symptoms in men with hyperreflexia following relief of the obstruction. PMID- 2579253 TI - Testicular cancer in homosexual men with cellular immune deficiency: report of 2 cases. AB - Embryonal cell carcinoma of the testis was seen in 2 homosexuals with peripheral lymphadenopathy of the head and neck, and abnormal cellular immunity measured by reduced T helper cells and increased T suppressor cells. One patient had no history of venereal disease but had taken marijuana, nitrites and methyl dextroamphetamines regularly. The other patient had a history of syphilis, gonorrhea, hepatitis and venereal warts but rarely used inhalant recreational drugs. Both patients had smoked cigarettes. Neither patient had any known risk factors that predisposed to testicular cancer. Biopsy of a supraclavicular lymph node in 1 patient showed histological features of reactive follicular hyperplasia similar to those described previously in the acquired immune deficiency syndrome. These cases of testicular cancer increase the spectrum of rare cancers developing in young male homosexuals with acquired cellular immune abnormalities. PMID- 2579254 TI - A, B and H antigens in normal urothelium: an immunohistochemical study using monoclonal antibodies with the avidin-biotin complex technique. AB - Immunohistochemical staining for the A, B and H blood group antigens was studied in 61 normal human ureters using monoclonal antibodies with avidin-biotin complex application. Thirty-seven of these were archival material, and 24 were processed prospectively. In 100 per cent of the prospectively processed ureters, A, B and H antigens were demonstrated corresponding to the blood type of the source. Archival material stained for A, B and H 65 per cent, 50 per cent and 100 per cent of the time, respectively. Serial sampling of prospectively processed ureters showed diminution of staining with prolongation of immersion in formalin. A characteristic staining pattern was found in ureters from patients with type B blood. PMID- 2579255 TI - Monoclonal antibodies to human urothelial cell lines and hybrids: production and characterization. AB - Eleven independent monoclonal antibodies, the LBS series, were isolated after immunization of mice with RT112 cells, a continuous cell line derived from a transitional cell carcinoma of the human bladder. These antibodies were tested by indirect immunofluorescence on a panel of 28 human cell lines, of which 17 were urothelial carcinoma-derived, 4 of non-urothelial carcinoma origin, 3 fibroblast cell lines, 4 lymphoblastoid lines and 7 murine cell lines. Also tested were 7 somatic cell hybrid clones derived by fusion of human RT112 cells with murine bladder carcinoma MB63T/H cells. None of the LBS antibodies reacted with mesenchyme-derived cells, although all reacted with RT112 cells. On the basis of reactivity with the cell line panel, the antibodies were divided into 3 groups. Group I (LBS-1 and 19) reacted with all human epithelium-derived cell lines. Group II (LBS-2, 8, 15 and 17) reacted only with human urothelium-derived cells, tending to recognise the least anaplastic types. Group III antibodies (LBS-10, 20A, 20B, 21 and 34) were urothelium-specific on the human continuous cell line panel, but additionally reacted with murine urothelial and epithelial cell lines. The 6 human-specific antibodies (Group I and II) were used for preliminary analysis of human gene expression in a series of 7 mouse X human urothelial somatic cell hybrids. Each hybrid reacted with at least 1 LBS antibody, although there were changes in gene expression with time in culture, indicating both loss and unmasking of human genes. These data suggest the LBS-series antibodies recognise different determinants associated with epithelial and urothelial cell differentiation, and thus may be valuable probes in the study of normal differentiation and malignant transformation in human urothelial cells. PMID- 2579256 TI - Nasal sprays and perforation of the nasal septum. PMID- 2579258 TI - [Clinical training at an operation room--antiseptic handling of a check list]. PMID- 2579257 TI - A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. AB - Three hundred five patients with advanced pancreatic and gastric carcinoma were randomly assigned to treatment with fluorouracil, fluorouracil plus doxorubicin (Adriamycin) (FA), or fluorouracil plus doxorubicin plus mitomycin (mitomycin C) (FAM). All regimens were equivalent with regard to patient survival. There is no reasonable likelihood that either the FA or FAM regimen could produce a meaningful survival advantage over fluorouracil alone. Interval to disease progression, objective response rates, and palliative effects (improved performance, body weight, or symptoms) were essentially equivalent among the three regimens. With regard to toxicity, the FAM regimen produced more anorexia, nausea, vomiting, leukopenia, thrombocytopenia, and cumulative bone marrow suppression. Fluorouracil alone produced more stomatitis and diarrhea. Because of a failure to produce improved survival or palliation, unrewarded toxicity, and excessive cost, neither the FA nor FAM regimen can be recommended for the treatment of advanced pancreatic or gastric cancer. PMID- 2579259 TI - Isolation and characterization of clonal cell lines from a transplantable metastasizing rat mammary tumor, TR2CL. AB - The metastasizing rat mammary cell strain from the Ludwig Institute for Cancer Research (London Branch) which was originally developed from a benign rat mammary tumor induced by N-methyl-N-nitrosourea (CAS: 684-93-5), yielded single-cell cloned lines of isometric epithelial cells [rat mammary (Rama) 600-Rama 621] and one line of elongated cells (Rama 622); the former had a higher estrogen receptor content than the latter. All the representative epithelial cell lines tested (Rama 600, 603, and 617) failed to convert to elongated, myoepithelial-like cells or droplet cell/doming, alveolar-like cells in vitro. All representative cell lines tested induced tumors in syngeneic F344/N rats and CBA nu/nu mice, but only the epithelial lines metastasized to lungs and local lymph nodes in rats and to lungs in nude mice. The involved lungs and lymph nodes contained mainly intravascular thrombi and deposits in the subcapsular sinus, respectively. Tumors and metastases from the representative epithelial cell lines contained acinar and glandular structures together with an elongated cellular component. The Rama 622 tumors contained mainly spindle cells. Antisera to rat milk fat globule membranes and human keratins stained some of the epithelial and elongated cells in the Rama 600 tumors; less staining was observed in the Rama 622 tumors. None of the tumor cells stained with antiserum to myosin. Anti-laminin serum delineated a fragmented basement membrane in glandular elements and stained weakly the cytoplasm of the more elongated tumor cells. Ultrastructural analysis confirmed the identity of epithelial cells in the Rama 600 tumors, but no well differentiated myoepithelial cells were seen in either type of tumor. Since nonmetastasizing epithelial cells isolated directly from carcinogen-induced benign rat mammary tumors can differentiate to myoepithelial-like cells in vitro or when growing as tumors in animals, it is suggested that the development of the malignant phenotype is associated with a loss of this differentiating ability. PMID- 2579262 TI - [Laboratory diagnostic examinations of male adolescents in outpatient clinics and hospitals]. PMID- 2579260 TI - [Tumor markers and endocrinologic aspects in intracranial germinoma]. AB - This report outlines the endocrine abnormalities associated with intracranial germinoma in childhood. The presence of special tumoral markers as alpha 1 fetoprotein and beta-HCG could be of diagnostic value and is important in respect to therapy control. However the reported case shows that despite known radiosensitivity and appropriate radiotherapy localized tumor relapse may arise soon after treatment. PMID- 2579261 TI - Studies on the role of sodium- and potassium-activated adenosine triphosphatase inhibition in the pathogenesis of human hypertension. Changes in vascular and cardiac function following inhibition of the sodium pump in normotensive subjects and effects of calcium entry blockade. AB - An endogenous humoral factor which inhibits the sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) enzyme in vitro has been incriminated recently of playing a pathogenetic role in experimental and human hypertension. The present study was therefore performed in six healthy volunteers to investigate the hemodynamic consequences of an inhibition of this enzyme by ouabain, a potent and specific inhibitor of Na-K-ATPase. In addition, the role of intracellular calcium as a potential mediator was studied indirectly by the administration of nifedipine, a potent calcium entry blocker with predominant vasodilator properties. Intravenous administration of 8.5 micrograms ouabain/kg body weight inhibited red blood cell (RBC) - Na-K-ATPase by 49% which was accompanied by a significant increase in RBC - ATP and a decrease in intracellular potassium concentrations. This enzyme inhibition resulted in a 24% increase in peripheral vascular resistance. The parallel decrease in cardiac output and heart rate, however, prevented a rise in arterial pressure. This increase in vascular resistance was completely abolished by pretreatment with nifedipine (10 mg orally). In the absence of an effect of nifedipine on Na-K ATPase, its attenuation of the vasoconstrictor effect of ouabain suggests that the effects of ouabain on the vascular smooth muscle cell are mediated by intracellular calcium. These results demonstrate that inhibition of the Na-K ATPase enzyme in vivo causes a marked peripheral vasoconstriction. They are also compatible with the concept that an endogenous inhibitor of Na-K-ATPase - in the presence of decreased baroreceptor reflex sensitivity due to blood volume expansion - may play a role in the pathogenesis of human arterial hypertension. PMID- 2579264 TI - [Capillary micromethod for determining the absorptive capacity of peripheral blood neutrophils]. PMID- 2579263 TI - [Laboratory evaluation of the efficacy of detoxicating therapy in peritonitis]. PMID- 2579265 TI - [Phospholipase activity, lipid peroxides and antioxidants of the bile in parasitic liver diseases]. PMID- 2579266 TI - [Dynamic study of cholesterol ester fractions in the blood of patients with viral hepatitis]. PMID- 2579268 TI - [Results of studies on the optimization of a photometric micromethod of determining cholinesterase activity in blood]. PMID- 2579267 TI - [Extraction-free method of determining free forms of corticosteroids in urine using competitive binding with transcortin]. PMID- 2579269 TI - [Role of the cyclic nucleotide system in immunoregulatory processes and methodological approaches to its study in evaluating human immune status]. PMID- 2579270 TI - [Effect of drugs on succinate dehydrogenase activity in a short-life culture of lymphocytes]. PMID- 2579271 TI - [Sorption of DNA on sheep erythrocytes using polyethylene glycol]. PMID- 2579272 TI - [Detection of sensitized lymphocytes in myocardial infarct by the active rosette formation inhibition reaction]. PMID- 2579273 TI - [Use of the isotope label 51Cr in cytolysis reactions]. PMID- 2579274 TI - [Chemiluminescent method of studying the functional activity of phagocytizing cells]. PMID- 2579275 TI - [Direct visual method for determining the killer bactericidal activity of peripheral blood neutrophils in healthy donors and patients]. PMID- 2579276 TI - [Highly sensitive variant of the passive hemagglutination reaction for detecting hepatitis B virus surface antigens]. PMID- 2579277 TI - [Efficient scheme for isolating and identifying the principal causative agents of acute bacterial meningitis]. PMID- 2579278 TI - [Method of quantitative determination of the microbial colonization of wounds]. PMID- 2579280 TI - [Apparatus for concentrating a gas sample in chromatographic analysis]. PMID- 2579279 TI - [Use of statistical parameters for determining the distribution of random errors in laboratory practice]. PMID- 2579281 TI - [Modified rapid method for detecting lupus erythematosus cells using the MM-3M magnetic mixer]. PMID- 2579282 TI - [Combination staining for nucleic acids in lymphocytes]. PMID- 2579283 TI - [Morphologic characteristics of cells in the blast crisis of myeloleukosis]. PMID- 2579284 TI - [Laboratory diagnosis of opisthorchiasis]. PMID- 2579285 TI - [Method of studying lipid peroxidation]. PMID- 2579286 TI - [Method of determining free oxyproline in blood]. PMID- 2579287 TI - [Medium for differentiating staphylococcal species]. PMID- 2579288 TI - [Methodology and interpretation of the results of the atropine test]. PMID- 2579290 TI - Guinea pig T lymphocyte development analyzed by enzyme histocytochemistry, monoclonal antibodies, and flow cytometry. AB - Studies of T (thymus-derived) lymphocyte ontogeny in the guinea pig have been hampered by the lack of suitable antigenic or other markers for various T cell subpopulations in this species. Monoclonal antibodies that recognize three distinct surface proteins of guinea pig T cells and react with all peripheral T cells have been used in combination with membrane alkaline phosphatase (AP) to characterize stages of guinea pig T cell development and to determine anatomical localization of different T cell subpopulations. Flow cytofluorographic analysis of thymus, spleen, and lymph node lymphocytes was used to characterize monoclonal antibody specificity. Cortical thymocytes in tissue sections expressed membrane AP activity and contained nuclear terminal deoxynucleotidyl transferase; medullary thymocytes reacted strongly with one of the monoclonal antibodies (8BE6), minimally with a second (5CD2), and not at all with a third (11AE3). In contrast, polyclonal rabbit antiguinea pig T cell antiserum reacted with both cortical and medullary thymocytes. Staining of tissue sections of lymph node and spleen revealed AP+ lymphocytes to be present peripheral to the mantle region of lymph node follicles and to be randomly scattered throughout the splenic red pulp. T cells reactive with monoclonal antibodies were located primarily in paracortical regions of lymph node and the central region around the periarteriolar regions of the spleen. Dual staining of frozen sections and cell suspension of guinea pig lymphoid tissues for AP activity and surface proteins unique to T cells showed that AP+ cells lacked T cell markers. Dual staining for AP activity and surface immunoglobulins or esterase activity showed that AP+ cells are not likely to be derived from either B cell or monocyte-macrophage lineages. AP+ cells in guinea pig secondary lymphoid tissue may represent a unique subset of lymphocytes of unknown function. PMID- 2579289 TI - Classification of human epithelia and their neoplasms using monoclonal antibodies to keratins: strategies, applications, and limitations. PMID- 2579291 TI - The role of the carbohydrate moiety on the size heterogeneity and immunologic determinants of human testosterone-estradiol-binding globulin. AB - Human testosterone-estradiol-binding globulin (hTeBG) has been purified to apparent homogeneity by several laboratories using procedures which, in most instances, were labor intensive. In this report, hTeBG was purified from pregnancy serum by a newly developed two step procedure involving sequential affinity chromatography and ion-exchange high performance liquid chromatography (ion-exchange HPLC). The purity of the final product was confirmed by silver stained SDS-polyacrylamide gel and reverse phase HPLC monitored at 206 nm. hTeBG purified by ion-exchange-HPLC maintained binding activity by Dextran coated charcoal (DCC) assay and size heterogeneity on SDS-polyacrylamide gels which were indistinguishable from those of the proteins purified by conventional chromatography. Removal of the carbohydrate moiety from the molecule by both enzymatic and chemical treatment reduced the apparent molecular size and eliminated lectin binding of hTeBG subunits. Deglycosylation did not, however, abolish or alter the distribution of the protomeric forms of this subunit. We conclude that hTeBG is a dimer whose monomer exhibits two protomeric forms which is not a result of carbohydrate heterogeneity. In addition, disialylated and deglycosylated hTeBG exhibited antigenic determinants identical to the native protein. PMID- 2579292 TI - Pitfalls in the Dextran-coated charcoal assay of estrogen receptors in breast cancer tissue. AB - This study investigated the influence of the degree of concentration of breast tumor cytosols on the apparent estrogen receptor content as measured by the Dextran-charcoal assay. It was found that the dilution of cytosols to 1-2 mg protein/ml frequently but not always causes highly underestimated receptor concentrations. This could not be explained by the protein loss through adsorption to the charcoal. The effect was also studied in the presence of gelatin, sodium molybdate or with limited trypsinization of the incubation mixture. Addition of 1 mg/ml gelatin in the Dextran-charcoal suspension was very useful in most cases in preventing dilution induced losses in receptor sites. Both trypsinization and addition of sodium molybdate produced increases in receptor concentrations that were not as susceptible to inactivation through dilution of the cytosol. These data suggest that the observed high variability in the dilution induced receptor losses can be explained by receptor heterogeneity: some receptor form(s) are either readily absorbed to or "stripped" by the charcoal particles. As a conclusion we recommend that in order to optimize the estrogen receptor assay as regards both binding sites and affinities the cytosol concentrations should be maintained as high as possible and a protein expander be included in the Dextran-charcoal suspension. Though sodium molybdate frequently gives considerable increases in estrogen binding sites it occasionally has an opposite effect. For this reason we hesitate to recommend its use in routine assays of estrogen receptors. PMID- 2579293 TI - Decriminalization of public drunkenness: response of the health care system. AB - Thirty-four U.S. jurisdictions have fully implemented the major provisions of the Uniform Alcoholism and Intoxication Treatment Act, calling for the decriminalization of public drunkenness. Available evidence strongly suggests that the Uniform Act has only imperfectly achieved two of its principal goals: the redirection of responsibility for the public inebriate from the criminal justice system to the health care system, and the rehabilitation of public inebriates through participation in a continuum of health care services. Explanations for these failures may lie in both the concept of detoxication and in the effectiveness with which the concept has been implemented. However, additional research is needed to provide adequate data for fully assessing the impact of the act and explaining its apparent failure. PMID- 2579295 TI - Cancer of the head of the pancreas: an institutional review with emphasis on surgical therapy. AB - A clinical review of 461 patients with adenocarcinoma of the pancreas is presented. Seventy-nine percent of the group underwent laparotomy, including laparotomy and biopsy (n = 134), bypass procedures (n = 207), and radical resection (n = 24). The operative mortality following cholecystoenterostomy or choledochoenterostomy was similar but survival was greater following the latter procedure. Thirteen percent having biliary bypass alone needed later gastric bypass. Radical resection is recommended under favorable conditions (6.6% in this series). The five-year survival in this group was 12.5% and the operative mortality was 9% over the last 10 years. PMID- 2579294 TI - Early recurrence following induction chemotherapy for stage IV head and neck cancers: rationale for additional therapy. AB - Twenty patients with Stage IV neoplasms of the head and neck were treated with two induction cycles of cis-platinum, bleomycin and methotrexate. Eight of eleven operable patients and five of nine inoperable patients responded prior to surgery and/or radiation, including three CRs. Toxicity was mild. There were two early local recurrences but no systemic metastases among the resectable patients. Perhaps initial therapy should be used to select patients with chemoresponsive tumors who might benefit from additional chemotherapy after surgery. PMID- 2579296 TI - 14th annual UCLA symposia. Nuclear envelope structure and RNA maturation. January 12-19, 1985. Abstracts. PMID- 2579297 TI - Monoclonal antibodies to epithelial membrane antigen and human milk fat globule mucin define epitopes expressed on other molecules. PMID- 2579298 TI - Pain relief for the terminally ill. PMID- 2579299 TI - High-dose intravenous gammaglobulin: a cautionary note. PMID- 2579300 TI - Maternal weight adjustment and low serum alpha-fetoprotein values. PMID- 2579301 TI - Prenatal diagnosis of Cockayne's syndrome. AB - Cockayne's syndrome (CS) was diagnosed prenatally by examination of amniotic cells cultured in vitro. RNA synthesis after irradiation with ultraviolet light was abnormal in cells from a fetus with CS but not in cells from a fetus which was normal. The procedure is simple and rapid and the outcome of the test in two cases (one positive, one negative) was unambiguous. PMID- 2579302 TI - Non-A, non-B hepatitis after intravenous gammaglobulin. PMID- 2579304 TI - Approved names for interferon. PMID- 2579303 TI - Inosine pranobex for mucocutaneous herpes. PMID- 2579305 TI - Do pregnancy complications contribute to neurodevelopmental disability? AB - In the Dundee Development Screening Programme all children born in Dundee in 1974 and 1975 were screened at intervals during infancy and childhood. The obstetric and neonatal antecedent factors in 300 of the 322 singleton children with neurodevelopmental disability (index group) were compared with those of the 600 children of normal development born immediately before and after each child with disability (control group). Low social class was associated with mental retardation, global delay, speech delay, and behavioural disorder, but not with cerebral palsy or motor delay. With the exception of cerebral palsy, strong associations were found between all categories of disability and severe hypertension, unclassified antepartum haemorrhage, and preterm uterine activity. Cerebral palsy was not associated with antepartum complications, but was with fetal tachycardia during labour. Our data suggest that neurodevelopmental disability may, in many cases, originate during pregnancy and delivery. PMID- 2579306 TI - AFP screening and Down syndrome. PMID- 2579307 TI - [Endotube as a palliative measure in stenosing cancer of the esophagus and cardia]. AB - 93 patients with advanced carcinoma of the esophagus or cardia were treated by positioning an endoprothesis under combined endoscopic and radiological control. Before this procedure the esophagus had been dilated - in 31 cases with our new multistage bougie. 14% of patients died in the hospital, 7,5% of these as a consequence of the procedure described. If no complications occur, the patients can be discharged from the hospital 24 hours later. Swallowing is improved definitely, mean survival time of our group was 10.9 weeks. Complications occurring later are mostly due to technical problems of the endoprothesis. Endoscopic positioning of the endoprothesis is a satisfactory palliative procedure. Positioning the endoprothesis by surgery to day is outdated. PMID- 2579308 TI - Effects of acute and chronic administrations of phencyclidine on the levels of serotonin and 5-hydroxyindoleacetic acid in discrete brain areas of mouse. AB - The effects of phencyclidine (PCP) on the levels of serotonin (5-HT) and 5 hydroxyindoleacetic acid (5-HIAA) in discrete brain areas of mouse were investigated. Following a single administration, PCP significantly increased at 60 min the level of 5-HT but not 5-HIAA in the cortex. However, acute administration of PCP induced no changes of 5-HT and 5-HIAA levels in other brain areas investigated. On the other hand, chronic treatment of PCP produced a significant increase the striatal 5-HT and 5-HIAA levels by about 30% and 20%, respectively. These increased levels were gradually returned to the control levels, and there was no difference of these levels between the control group and the 48 hr withdrawal group. The changes of 5-HT level in the hypothalamus were similar to those in the striatum. These results suggest that the pharmacological actions of PCP and tolerance development to PCP may be related to the functional changes of serotonergic neuronal activity. PMID- 2579309 TI - Effects of diazepam on soman-induced brain neuronal RNA depletion and lethality in rats. AB - Studies were conducted to determine effects of the benzodiazepine anticonvulsant diazepam on soman induced brain neuronal RNA depletion and lethality in rats. Quantitative azure B-RNA cytophotometry was used to monitor RNA responses of cerebrocortical (layer V) and striatal neurons following dosages of 0.5, 0.9 and 1.5 LD50 soman (LD50 = 135 micrograms/kg, sc), whereas mean time of death and 24 h survival following 0.8, 1.2 and 1.5 LD50 were used to assess the antidotal efficacy of diazepam (2.2 mg/kg, im) pretreatment. Soman produced dose-dependent RNA depletion in both brain regions. This RNA impairment was almost completely prevented by diazepam, although neuronal RNA contents were generally slightly lower than corresponding control values. However, diazepam pretreatment was not associated with any change in mean time of death or in 24-h survival. The overall data suggest that excessive neural activity per se may underlie the genesis of soman-induced central metabolic impairments, but also appear to effectively dissociate epileptiform activity from lethal actions of soman. PMID- 2579310 TI - Stereospecificity of SP1 and SP2 substance P receptors. AB - Previous studies with N-terminal fragments of substance P (SP) have suggested the existence of two separate SP receptor populations. SP1 receptors are found in guinea pig ilea and rat colons. SP2 receptors are found in mouse spinal cords and rat salivary glands. We have now found that substitution of Gly9 in substance P's C-terminal hexapeptide leads to an analog (L-Pro9 SP6-11) which selectively and potently stimulates SP2 receptors. In contrast, substitution of the same residue with D-Proline results in a potent and selective agonist for SP1 receptors. The data dramatically confirm the distinction between SP1 and SP2 receptors and demonstrate that the two receptors have distinct stereochemical architectures. PMID- 2579311 TI - Characterization of elevated plasma alkaline phosphatase activity in genetically obese mice. AB - Alkaline phosphatase activity in obese mice (C57BL/6J ob/ob) was significantly increased from 18 to 63 weeks of age when compared to that of their lean controls (C57BL/6J +/?). In 5 week old animals, the earliest age examined, the circulating activity of alkaline phosphatase was similar in both obese mice and their lean counterparts. To characterize the circulating alkaline phosphatase activity in the obese mouse and its lean counterpart, the response of the enzyme to fasting, various inhibitors, heat inactivation, and urea denaturation was examined and compared. L-homoarginine and L-p-bromotetramisole inhibited to a large extent the circulating activity of alkaline phosphatase in both obese mice and their lean controls in the fed state, while L-phenylalanine had essentially no effect. Even though the response of alkaline phosphatase in plasma to several inhibitors was similar, the rate of denaturation by urea of enzyme activity in plasma was significantly slower in obese mice than in their lean controls in the fed state. While the rate of inactivation of alkaline phosphatase activity in plasma for the initial two minutes at 56 degrees C was similar in obese mice and their lean counterparts, the subsequent rate of heat inactivation was significantly slower in the plasma from obese mice. Thus, both obese and lean mice in the fed state have a circulating activity of alkaline phosphatase in plasma with a greater contribution from a skeletal isoenzyme and a lesser one of intestinal origin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579312 TI - Solubilization and reconstitution of the calcium release channel of skeletal sarcoplasmic reticulum. AB - Fragmented heavy sarcoplasmic reticulum was solubilized by cholate, and proteins were subsequently fractionated by using diethylaminoethyl-cellulose (DEAE cellulose) column chromatography. A fraction was collected in which proteins with molecular weights between 31,000 and 45,000 u were major components. This fraction, when incorporated into Ca2+ -loaded liposomes, facilitated the Ca2+ efflux. The rate of efflux was regulated by the external Ca2+ concentration, reaching a maximum at 3 microM Ca2+. The Ca2+ efflux was suppressed by Mg2+. PMID- 2579314 TI - Management of cancer pain. PMID- 2579313 TI - Production of monoclonal antibodies against the carbohydrate of group A streptococci. AB - Mouse hybridomas were isolated by fusing P3.X63.Ag8-653 myeloma cells with spleen cells from BDF1 mice repeatedly immunized with Streptococcus pyogenes type 3 ATCC 12384. Two out of 480 growing cultures secreted antibodies against the bacterial strain used as immunogen, as evaluated by an ELISA assay. After cloning the most representative continuously growing clone, 1-181, the binding specificity of these monoclonal antibodies was determined using either Streptococci with carbohydrate of different group or different bacteria strains. Binding properties suggest that the 1.181 monoclonal antibodies specifically recognize the carbohydrate moiety of Streptococci group A. PMID- 2579315 TI - [Headache caused by drugs]. PMID- 2579316 TI - Parotid kallikrein secretion in the rat after alterations of electrolyte transport and cAMP activity. AB - The effects of pharmacologically induced alterations of electrolyte transport and cAMP activity on kallikrein secretion - measured as amidolytic activity - in rat parotid gland were tested in vivo. Changes in transepithelial sodium/potassium transport caused a significant alteration of parotid kallikrein handling. Amidolytic activity was inhibited by sodium channel blockade (via amiloride) and stimulated by an increased sodium influx (via the sodium ionophore monensin). Enhanced intracellular cAMP activity (via dibutyryl cAMP and theophylline) caused a significant increase of ductal kallikrein and potassium secretion. Alterations of intracellular calcium-ion concentration (via A 23187 and verapamil) did not influence parotid kallikrein secretion. Parotid kallikrein secretion seems to be dependent on intracellular sodium and cAMP concentration. PMID- 2579317 TI - Comparison of the cellular and RNA-dependent effects of sangivamycin and toyocamycin in human colon carcinoma cells. AB - The effects of the pyrrolopyrimidine antibiotics sangivamycin and toyocamycin on the synthesis of RNA and protein, ribosomal RNA processing, and cell viability were examined in colon carcinoma cell line HT-29. Exposure for 24 hr to toyocamycin caused an exponential type of cell lethality resulting in a 4-log reduction of cell viability, while sangivamycin produced a gradual and self limiting type of cell lethality resulting in a 1-log reduction of cell viability. Toyocamycin, at a concentration of 1 microM produced total cessation of precursor rRNA processing, while 10 microM sangivamycin produced little or no effect on processing. On the contrary, sangivamycin caused a significant decrease in protein synthesis after 6 hr, while toyocamycin had less effect. The inhibition of protein synthesis by sangivamycin results from an inhibition of the formation of complexes essential to the initiation of protein synthesis. The results suggest that the mechanisms of action of these closely related agents are quite distinct. The marked loss of cell viability caused by toyocamycin correlates with its effect on rRNA processing, while the slow inhibition of protein synthesis appears to be secondary to the loss of ribosome synthesis. On the other hand, the lesser cytotoxicity produced by sangivamycin results from a more direct effect on protein synthesis. Importantly, cells are much less capable of resuming normal proliferative activity after 24 hr of impaired rRNA processing than after a similar interval of reduced protein synthesis. PMID- 2579318 TI - Enhanced bleomycin-induced DNA damage and cytotoxicity with calmodulin antagonists. AB - A wide variety of structurally different calmodulin antagonists enhanced the cytotoxicity of bleomycin A2 to leukemic L1210 cells. This potentiation occurred with nontoxic concentrations of calmodulin antagonists. The most potent blockers of L1210 calmodulin activity, melittin and mastoparan, were the most potent potentiators of bleomycin A2 cytotoxicity. Less potent agents such as pimozide, a diphenylbutylpiperidine, trifluoperazine and chlorpromazine, phenothiazines, and W-7, a naphthalene sulfonamide, required higher concentrations for potentiation of bleomycin A2-induced cytotoxicity, while homologs that lack anticalmodulin activity failed to increase the cytotoxicity seen with bleomycin A2. The potentiation of bleomycin A2 cytotoxicity was not due to an elevated cellular content of bleomycin A2 or to inhibition of bleomycin A2 inactivation. Using alkaline elution techniques, we found that pimozide increased bleomycin A2 induced DNA damage in intact L1210 cells. Pimozide did not, however, directly increase the formation of reactive species by bleomycin as measured by single or double strand breakage of covalently closed circular DNA. Thus, the potentiation of bleomycin cytotoxicity by these agents appears to be mediated by an increased damage to cellular DNA; this may be due to inhibition of DNA repair. The hypothesized calmodulin-dependent mechanism was not shared by all agents that caused breaks in DNA because no potentiation in cytotoxicity was observed when calmodulin antagonists were combined with either etoposide or X-irradiation. PMID- 2579319 TI - A quantitative study of [3H]D-Ala2-D-Leu5-enkephalin binding to rat brain membranes. Evidence that oxymorphone is a noncompetitive inhibitor of the lower affinity delta-binding site. AB - The mechanism by which mu ligands inhibit the binding of prototypic delta agonists to preparations of brain membranes is controversial. Most investigators assume competitive inhibition. In this study, we examine the interaction of the mu agonist oxymorphone and delta agonist DSTLE (D-Ser2-Thr6-Leu-enkephalin) with [3H]D-Ala2-D-Leu5-enkephalin (DADL) binding to membranes of rat brain. According to the two-site competitive model, mu ligands are competitive inhibitors at both sites. The two-site allosteric model supposes that mu ligands are competitive inhibitors at one binding site, and noncompetitive inhibitors at the other binding site. Quantitative analysis of DSTLE and oxymorphone binding demonstrated that the two-site allosteric model fit the data significantly better than did the two-site competitive model, and that oxymorphone is a noncompetitive inhibitor of the lower affinity [3H]DADL-binding site. Autoradiographic studies demonstrated that the lower affinity [3H]DADL-binding site (mu-noncompetitive binding site) had an anatomical distribution apparently indistinguishable from that obtained with [3H]oxymorphone (type I pattern), supporting the hypothesis that the lower affinity delta-binding site is the delta-binding site of an opiate receptor complex consisting of interacting mu- and delta-binding sites. PMID- 2579320 TI - Transfection of mouse fibroblast cells with a promoterless herpes simplex virus thymidine kinase gene: number of integrated gene copies and structure of single and amplified gene sequences. AB - Plasmids carrying the herpes simplex virus thymidine kinase (tk) gene were used to transfect thymidine kinase-deficient cells of the mouse fibroblast cell line LM(tk-). Individual cell clones were cultivated in selective hypoxanthine aminopterin-thymidine medium to determine the number of integrated plasmid copies which was almost always in the range of one to three copies per genome. In contrast, cells transfected with plasmids carrying a promoterless "truncated" tk gene typically contained between 10 and 25 copies per genome. Surprisingly, when the truncated tk gene was transfected together with a simian virus 40 DNA segment, including its transcriptional enhancer, the number of integrated tk gene copies was always low, between one and three copies per genome. We have analyzed the genomic organization of integrated truncated tk genes by blot hybridization of restricted cellular DNA and concluded that integrated units of plasmid DNA molecules are arranged in tandem arrays which remain stable in most cases for many cell generations. In only 1 of ca. 20 cell clones did we observe a retraction and expansion of the number of integrated promoterless tk genes as a response to the removal or readdition of selective pressure. Surprisingly, the thymidine kinase activity determined in extracts from cells growing in selective hypoxanthine-aminopterin-thymidine medium (high numbers of integrated tk gene copies) was nearly the same as the enzymatic activity in cells growing in nonselective medium (low copy numbers). Moreover, Northern blots of polyadenylated RNA, extracted from cells growing under selective and nonselective conditions, showed that, in both cases, the major species of tk-specific transcripts was ca. 1.5 kilobases in size, as expected for a tk-specific mRNA containing the entire coding region of the gene. Thus, disproportionate DNA replication appeared not to be essential for an active tk gene expression in these cells. We discuss possible pathways leading to the formation of tandem arrays of integrated truncated tk genes and the conditions required for disproportionate DNA replication in the unique case in which we found a retraction and expansion of tk gene copy numbers as a response to selective growth conditions. PMID- 2579321 TI - RNA sequence containing hexanucleotide AAUAAA directs efficient mRNA polyadenylation in vitro. AB - To determine whether a specific nucleotide sequence is required to direct polyadenylation of a simian virus 40 early pre-mRNA in a soluble HeLa whole-cell lysate, we constructed a series of rearranged and deleted DNA templates, transcribed them in vitro, and determined whether the resultant RNAs could be polyadenylated when incubated in whole-cell lysate. When a 237-base-pair DNA fragment encoding the 3' end of the simian virus 40 early pre-mRNA was transferred to recombinant plasmids encoding RNAs that were not substrates for polyadenylation, the resultant RNAs could now be polyadenylated efficiently. In one case, the chimeric RNA was polyadenylated even more efficiently than was the original simian virus 40 early transcript. Analysis of the RNAs produced from the deletion mutant templates revealed that only RNAs containing at least one copy of the AAUAAA sequence situated near the 3' end and implicated in 3'-end formation and polyadenylation in vivo could be polyadenylated in vitro. Surprisingly, this sequence directed polyadenylation of pre-mRNAs not only when near the RNA 3' end, i.e., 50 nucleotides or less away, but also when the 3' end was situated over 400 nucleotides downstream. Thus, our results show that a polyadenylic acid polymerase activity in HeLa lysates can recognize a specific nucleotide sequence in pre-mRNA and then, in the absence of the nucleolytic cleavage that presumably occurs in vivo, locate the RNA 3' end and use it as a primer for polyadenylic acid synthesis. PMID- 2579322 TI - Sequences upstream of c-mos(rat) that block RNA accumulation in mouse cells do not inhibit in vitro transcription. AB - An unusual feature of the c-mos oncogene is the lack of expression in mouse tissues. Recombinant plasmids that contain the strong adenovirus late promoter and different amounts of cellular DNA 5' to c-mos(rat) were constructed and tested in transfection and transcription assays. The cellular sequences inhibit RNA accumulation in mouse but not human cells and do not inhibit in vitro transcription of the plasmid DNAs. PMID- 2579323 TI - Amplification and expression of a cellular oncogene (c-myc) in human gastric adenocarcinoma cells. AB - Three of 16 human gastric adenocarcinoma samples, maintained as solid tumors in nude mice, were found to carry amplified c-myc genes. In two samples with a high degree of c-myc DNA amplification (15- to 30-fold), double minute chromosomes were observed in karyotype analysis. The level of c-myc RNA was markedly elevated in a rapidly growing and poorly differentiated tumor, whereas it was only slightly elevated in a slowly growing and more differentiated tumor. PMID- 2579324 TI - Study of the antigenic structure of human serum albumin with monoclonal antibodies. AB - Analysis of the antigenic structure of human serum albumin was undertaken using monoclonal antibodies. Nineteen antibodies were prepared and their specificities were studied using fragments which encompass the whole sequence of the albumin molecule. These antibodies recognized 13 different epitopes which are different from the one previously identified with two other monoclonal antibodies [Doyen et al., Immun. Lett. 3, 365-370 (1981)]. Among those 13 different epitopes, six were overlapping. Four epitopes were located on the N-terminal half of the albumin molecule. One of these required integrity of methionine 87 and the other three were overlapping and located around methionine 123. Eight epitopes were located on the C-terminal half of the albumin. Two of them were within the sequence, 330 422 and 299-496 respectively; the other six appeared to be topographic determinants which were altered or lost in the albumin fragments. A last epitope could not be located on any region of albumin. Four monoclonal antibodies directed against a given portion of the albumin molecule reacted slightly with another part of albumin, thus confirming the existence of an intramolecular cross reactivity between the different domains of human albumin. PMID- 2579325 TI - Specificity and cross-reactivity of synthetic peptides derived from a major antigenic site of influenza hemagglutinin. AB - A synthetic peptide corresponding to sequence 138-164 of influenza hemagglutinin elicited in rabbits antibodies that recognized different parts of the peptide, namely the loop region (139-146) and the rest of the peptide, region 147-164. This was shown both by direct binding and by competitive-inhibition experiments. Individual antisera differed in their specificity. The contribution of the Asp residue at position 144 to the antigenic specificity was shown in various inhibition assays. These data are in accordance with the reported effect of the exchange Gly----Asp on the serological specificity of influenza virus. PMID- 2579326 TI - Studies on artificial oligosaccharide-protein antigens: induction of precipitating antibodies to defined epitopes on natural and synthetic dextrans and mannans. AB - Seventeen di- and trisaccharides, composed of alpha-1-6-, alpha-1-2-, alpha-1-3- and alpha-1-4-linked glucosyl and alpha-1-6- and alpha-1-2-linked mannosyl residues, were synthesized. The oligosaccharides (OS) were transformed into the corresponding 2-(4-aminophenyl) ethyl alpha-D-glucosides or mannosides, which were either diazotized or converted into isothiocyanato derivatives and then coupled to BSA, edestin or hemocyanin to give artificial antigens. In this way immunogenic analogues of branched natural and linear synthetic dextrans, linear synthetic mannans and glucomannans were obtained. Upon immunization of rabbits with these conjugates, antibodies to the OS moieties carrying alpha-1-6, alpha-1 2 and alpha-1-3 glucosyl and alpha-1-6 mannosyl residues were elicited. These antibodies cross-reacted with and precipitated natural or synthetic polymers carrying the corresponding epitope pattern. The minimal size of an immunogenic OS residue required for cross-reactivity with the corresponding polymer was found to be either two or between one and two monosaccharide units. To obtain maximum and reliable elicitation of anti-OS antibodies of IgG isotype the use for coupling of an OS density corresponding to 10-25 moles of OS/mole of BSA is recommended. Other strongly immunogenic carriers may be used. In the case of homopolymers, each OS residue should have a length of at least six-eight sugar units. PMID- 2579328 TI - A glycoprotein of molecular weight 85,000 on human cells of B-lineage: detection with a family of monoclonal antibodies. AB - Immunization of BALB/c mice with glycoproteins purified from a detergent extract of human chronic lymphocytic leukemia (CLL) cells by affinity to Lens culinaris lectin led to the production of several monoclonal antibodies with similar reactivity. One of the antibodies, 50B4, was purified and the corresponding antigen was isolated from a B-lymphoblastoid cell line extract by affinity chromatography to the 50B4-IgG immunoadsorbent. Co-purification of the antigenic activities associated with five other monoclonal antibodies was achieved. Purified and radiolabelled 50B4 antigen could be specifically immunoprecipitated not only by 50B4 but also by the other five antibodies. SDS-PAGE analysis revealed that all antibodies precipitated the same component, a polypeptide chain of apparent mol. wt 85,000 under reducing conditions. Competitive-binding studies between the purified antibodies indicated the presence of two distinct epitopes on the antigen. The epitopes, each recognized by three different antibodies, were equally accessible on the cell surface of either a B-CLL (3 X 10(5) molecules/cell), a B-lymphoblastoid cell line (11 X 10(5) molecules/cell) or two acute lymphocytic leukemia (ALL) cell lines of pre-B phenotype (5 X 10(5) and 0.8 X 10(5) molecules/cell respectively). Although the antigens purified from the strongly positive ALL cell line gave a gel pattern identical to that of the B lymphoblastoid cell line, the antigens purified from the B-CLL extract were resolved into two distinct glycosylated polypeptides of mol. wts 85,000 and 77,000 under reducing conditions. The distribution of the antigen(s) is not restricted to cells of the B-lineage as mature T-cells and a variety of non hematopoietic cell types express both epitopes of the antigen(s). PMID- 2579327 TI - Allotypic and isotypic specificities of rabbit IgM: localization to the Fab mu or Fc mu fragments. AB - IgM from trypanosome-infected rabbits was digested with trypsin under different conditions to obtain Fab mu or Fc5 mu fragments suitable for analysis with anti allotype and anti-isotype antibodies. The Fab mu but not the Fc5 mu fragment was shown to have the n-locus allotypic specificities, n80, n81, n82, n83 and n87, characteristic of the IgM class of immunoglobulins. Thus, the n82 and n83 allotypic specificities, conformationally dependent on the a VH locus for expression, and the n80, n81 and n87 allotypic specificities, independent of the a VH locus for expression, are in either the CH1 or CH2 domain of IgM heavy chains. In addition, two high-affinity mouse monoclonal antibodies (MoAbs) specific for IgM and able to bind IgM in direct-binding radioimmunoassays were produced and characterized. One MoAb (3C1) was specific for an isotypic determinant (epitope) in the Fab mu fragment, presumably in the CH1 or CH2 domain, whereas another MoAb (8C2) was specific for an isotypic epitope in the Fc5 mu fragment, presumably in the CH3 or CH4 domain. The proximity of the n locus allotypic specificities (CH1 or CH2 domain) to the VH domain is consistent with the finding that some IgM allotypic specificities are expressed only in conjunction with certain a VH locus allotypic specificities. PMID- 2579329 TI - Antibodies elicited by influenza virus hemagglutinin fail to bind to synthetic peptides representing putative antigenic sites. AB - A number of peptides of the hemagglutinin (HA) of X-31 influenza virus have been synthesised. The amino acid sequences of some of these peptides represent regions of HA which have been postulated [Wiley et al., Nature, Lond. 289, 373-378 (1981)] to form the antigenic sites of this molecule. Animals were immunized with free peptide or peptide conjugated to a carrier and the resulting antisera examined for their capacities to bind to homologous peptide, whole HA, reduced and alkylated HA, and intact virus. Not all peptides examined in this way were immunogenic. Only antibodies raised against the C-terminus of HA1 peptide displayed binding to virus. This antiserum bound to the intact HA but not to the reduced and alkylated form of the molecule. These results raise questions as to the feasibility of using synthetic peptides of the influenza HA in short linear sequences to elicit neutralising antibody. PMID- 2579330 TI - Effect of pH on the mutagenic and killing potencies of ICR-170 in ad-3 tests of Neurospora crassa. PMID- 2579331 TI - Measurement of cytochrome P-450 dependent dealkylation of alkoxyphenoxazones in hepatic S9s and hepatocyte homogenates: effects of dicumarol. PMID- 2579332 TI - Autoradiographic detection of HPRT variants of human lymphocytes resistant to RNA synthesis inhibition. AB - The feasibility of using RNA synthesis in freshly isolated, human peripheral blood lymphocytes to detect 6-thioguanine (TG)- and 8-azaguanine (AG)-resistant variants in an autoradiographic assay similar to that of Strauss and Albertini (1979) has been evaluated. In phytohemagglutinin (PHA)-stimulated cultures RNA synthesis and HPRT activity began well in advance of DNA synthesis and increased in parallel during the first 44 h of culture. Introduction of TG or AG with PHA at the beginning of culture completely inhibited DNA synthesis during the first 44 h and reduced RNA synthesis to low levels within 24 h. When TG or AG was added after cells had been in culture for 38 h, DNA synthesis was reduced quickly while RNA synthesis was inhibited more slowly. An autoradiographic assay is described in which freshly isolated lymphocytes are cultured with PHA for 24 h, with or without TG or AG, then labeled with [3H]uridine for 1 h. TG-resistant and AG resistant variant frequencies for 2 normal individuals and a Lesch-Nyhan individual were determined with this assay. The variant frequencies for the normal individuals ranged from 0.46 to 10.6 X 10(-5) depending upon the selective conditions used. All the Lesch-Nyhan cells were resistant to 0.2 microM-2 mM AG; some were sensitive to 0.2 mM TG and most were sensitive to 2.0 mM TG. PMID- 2579333 TI - The action of anticlastogens in human lymphocyte cultures and their modification by rat-liver S9 mix. II. Studies with vitamins C and E. AB - The action of vitamins C (VC) and E (VE) on the clastogenic activity of trenimon (TR), cyclophosphamide (CP) and bleomycin (BM) was tested on cultures of human peripheral blood lymphocytes with and without addition of rat-liver S9 mix. In addition, the influence of both anticlastogens on the SCE-inducing activity of TR and CP was examined under the same conditions. A distinct dose-dependent anticlastogenic effect of VC was detected in the action of long-term treatment (24 h) with TR, if the vitamin was added to the cultures simultaneously with or before the clastogen. In the short-term tests (2 or 3 h clastogen treatment ending 23 h or 21 h before harvesting) simultaneous addition of both vitamins did reduce the chromosome-damaging action of TR whether S9 mix was present or absent. While VC also decreased the frequency of chromosome damage induced by S9-mix activated CP, VE was inactive under the same conditions. Neither vitamin significantly affected the chromosome-breaking activity of BM if S9 mix was absent, but they increased the clastogenicity of BM metabolized by S9 mix. In contrast to their anticlastogenic efficacy neither of the vitamins displayed any significant anti-SCE effect, nor were they active in affecting the inhibition of cell proliferation caused by TR or CP. PMID- 2579334 TI - Sharing of specific antigens by degenerating neurons in Pick's disease and Alzheimer's disease. PMID- 2579335 TI - Hypothesis: interference with axonal transport of neurofilament as a common pathogenetic mechanism in certain diseases of the central nervous system. PMID- 2579336 TI - Hematologically and genetically distinct forms of sickle cell anemia in Africa. The Senegal type and the Benin type. AB - Patients with sickle cell anemia vary in the hematologic and clinical features of their disease, in part because of variability in the presence of linked and unlinked genes that modify the expression of the disease. The hemoglobin S gene is strongly linked to three different haplotypes of polymorphic endonuclease restriction sites of the beta-like gene cluster (genes in the vicinity of the beta-globin gene)--one prevalent in Atlantic West Africa, another in central West Africa, and yet another in Bantu-speaking Africa (equatorial, East, and southern Africa). We have studied the differences in the hematologic characteristics of patients with sickle cell anemia from the first two geographical areas. We find that the Senegalese (Atlantic West Africa) patients have higher levels of hemoglobin F, a preponderance of G gamma chains in hemoglobin F, a lower proportion of very dense red cells, and a lower percentage of irreversibly sickled cells than those from Benin (central West Africa). We interpret these data to mean that the gamma-chain composition and the hemoglobin F level are haplotype linked and that the decrease in the percentage of dense cells and irreversibly sickled cells is secondary to the elevation in the hemoglobin F level. Patients with sickle cell anemia in the New World probably correspond to various combinations of these types, in addition to the still hematologically undefined haplotype associated with sickle cell anemia in the Bantu-speaking areas of Africa. PMID- 2579337 TI - Production of phenocopies by Kruppel antisense RNA injection into Drosophila embryos. AB - The demonstration that a specific messenger RNA can be functionally inactivated in vivo by hybridization to complementary polynucleotide sequences suggests a direct approach to the study of gene function in cells of higher organisms. The experiments described here were designed to inhibit, by complementary RNA sequences, a specific gene function affecting the fate of the Drosophila embryo. We used the SP6 vector in vitro transcription system to transcribe parts of the normally untranscribed (nonsense) strand of the Kruppel (Kr) gene into complementary Kr RNA (Kr antisense RNA). Wild-type Drosophila embryos, injected with this RNA, developed into phenocopies of Kr mutant embryos. PMID- 2579338 TI - Identification of antigen receptor-associated structures on murine T cells. AB - The specific antigen receptor on human and murine T lymphocytes is a heterodimer of relative molecular mass (Mr) 80,000-90,000 (80-90K) composed of two 40-50K disulphide-linked glycoprotein subunits. Peptide map analysis of the alpha- and beta-chains of receptor isolated from distinct tumour cell lines suggests the presence of both constant and variable regions. Unlike the antigen receptor on B lymphocytes (that is, surface immunoglobulin), the human T-cell antigen receptor seems to be non-covalently associated with another invariant structure recognized by monoclonal antibodies to the cell-surface antigens T3 and Leu 4 (refs 4, 5, 9, 12). Meuer et al. have demonstrated comodulation of the T3 structure and T-cell antigen receptor using anti-clonotypic and anti-T3 monoclonal antibodies. Furthermore, immunoprecipitation with anti-T3 weakly co-precipitates a small amount of the 80-90K heterodimer in certain conditions. The murine homologue of the Leu 4/T3 structure has not been identified, although Gunter et al. have suggested that Thy-1 may be the counterpart of Leu 4/T3 (ref. 13). Here we describe a Leu 4/T3-like structure, distinct from Thy-1, associated with the T cell receptor of a murine T-lymphoma cell line. PMID- 2579339 TI - Human genes for U2 small nuclear RNA map to a major adenovirus 12 modification site on chromosome 17. AB - U2 RNA is one of the abundant, highly conserved species of small nuclear RNA (snRNA) molecules implicated in RNA processing. As is typical of mammalian snRNAs, human U1 and U2 are each encoded by a multigene family. In the human genome, defective copies of the genes (pseudogenes) far outnumber the authentic genes. The majority or all of the 35 to 100 bona fide U1 genes have at least 20 kilobases (kb) of nearly perfect 5' and 3' flanking homology in common with each other; these U1 genes are clustered loosely in chromosome band 1p36 (refs 5, 7) with intergenic distances exceeding 44 kb. In contrast, the 10 to 20 U2 genes are clustered tightly in a virtually perfect tandem array which has a strict 6-kb repeating unit. We report here the assignment, by in situ hybridization, of the U2 gene cluster to chromosome 17, bands q21-q22. Surprisingly, this region is one of three major adenovirus 12 modification sites which undergo chromosome decondensation ('uncoiling') in permissive human cells infected by highly oncogenic strains of adenovirus. The two other major modification sites, 1p36 and 1q21, coincide with the locations of U1 genes and class I U1 pseudogenes, respectively. We suggest that snRNA genes are the major targets of viral chromosome modification. PMID- 2579341 TI - A functional correlate for the dihydropyridine binding site in rat brain. AB - Calcium channels, controlling the influx of extracellular Ca2+ and hence neurotransmitter release, exist in the brain. However, drugs classed as calcium antagonists and which inhibit Ca2+ entry through voltage-activated Ca2+ channels in heart and smooth muscle, seem not to affect any aspect of neuronal function in the brain at pharmacologically relevant concentrations. Yet the dihydropyridine calcium antagonists (for example, nitrendipine) bind stereospecifically with high affinity to a recognition site on brain-cell membranes thought to represent the Ca2+ channel and consequently, the physiological relevance of these sites has been questioned. However, activation of voltage-dependent Ca2+ channels can increase cytoplasmic Ca2+ and neurotransmitter release in neuronal tissue. We show here that Bay K8644, a dihydropyridine Ca2+-channel activator, can augment K+-stimulated release of serotonin from rat frontal cortex slices and that these effects can be antagonized by low concentrations of calcium antagonists. As 3H dihydropyridine binding to cortical membrane preparations resembles the binding in heart and smooth muscle where there are good functional correlates we conclude that the dihydropyridine binding sites in the brain represent functional Ca2+ channels that can be unmasked under certain circumstances. PMID- 2579340 TI - Demonstration by monoclonal antibodies that carbohydrate structures of glycoproteins and glycolipids are onco-developmental antigens. AB - The hope that hybridoma antibodies would reveal unique cell surface antigens during embryogenesis, differentiation and oncogenesis has been replaced by the realization that such antigens are mainly carbohydrate structures of glycoproteins and glycolipids occurring in many cell types. These findings either may reflect limitations in the methods of selection of hybridoma antibodies or may point to important roles for the diverse carbohydrate structures as receptors for regulators of cell growth and differentiation. PMID- 2579342 TI - Imunovir defended. PMID- 2579343 TI - Association of histone H1(0) with a gene repressed during liver development. AB - Histone H1(0) has a number of unusual properties that set it apart from other H1 subtypes (for review see ref. 1). For example, H1(0) synthesis is not strictly coupled to DNA synthesis, it is absent from the embryonic liver of mice (but present shortly after birth) and its synthesis is hormone-dependent in some of the glands of adult rodents. All the H1 subtypes differ in their DNA binding properties, and H1(0) has been shown to be preferentially associated with nuclease-resistant chromatin. These features suggest that the H1(0) may have a role in developmental gene control. To investigate this further, we have fractionated the H1(0)-containing nucleosomes of chromatin from adult mouse liver. We report here that the gene for alpha-fetoprotein, which is expressed in embryonic tissue but repressed soon after birth, is preferentially associated with the H1(0)-containing nucleosomes. The related gene for albumin, which is expressed in both embryonic and adult tissues, is absent from the H1(0) containing nucleosome fraction. These results support a role for histone H1(0) in the control of gene expression. PMID- 2579344 TI - [Sodium channels in electrically excitable membranes]. AB - Properties of sodium channels in electrically excitable membranes can be obtained from sodium currents, gating currents, sodium-current fluctuations and currents through single channels. Gating processes in sodium channels are related to intramembranous charge displacements and are modified by toxins, local anaesthetics and chemical agents. From the results a schematic diagram of a sodium channel can be derived. PMID- 2579345 TI - [Breast cancer in men in the Netherlands; a retrospective study in 104 patients]. PMID- 2579346 TI - Aging and diurnal rhythms of pineal serotonin, 5-hydroxyindoleacetic acid, norepinephrine, dopamine and serum melatonin in the male rat. AB - Pineal serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE) and dopamine (DA) were measured by high-pressure liquid chromatography with electrochemical detection and serum melatonin was measured by radioimmunoassay in rats aged 3 weeks, 8 weeks and 18 months. They were killed either at mid-light or mid-dark of a 12 h light:12 h dark cycle. Diurnal rhythms were observed for 5-HT and 5-HIAA in all ages studied while those for NE and DA were not observed in the 18-month-old animals. Pineal 5-HT and 5-HIAA were higher in 3-week-old rats at mid-dark, and lower at mid-light than in older animals. The pineal content of NE was lower in the 3-week-old rats at mid-dark and mid-light compared with that in the 8-week-old while the DA content was lower at mid-dark. In addition, pineal 5 HT, 5-HIAA, NE and DA were lower in the 18-month-old than in the 8-week-old animals at mid-dark. At mid-dark serum melatonin levels showed an age-related decrease. This study shows that an age-related decrease of pineal 5-HT, 5-HIAA, NE and DA can only be demonstrated at mid-dark and that the age-related decrease of melatonin may not be due to a decrease in sympathetic activity. PMID- 2579347 TI - Role of plasmin, thrombin, and antithrombin III as etiological factors in delayed cerebral vasospasm. AB - The fibrinolytic enzyme plasmin at 0.25 units/ml produced a contraction of isolated canine basilar arteries that developed slowly and was sustained for at least 2 hours. Plasmin and thrombin (1 unit/ml) acted synergistically to enhance the contractile response. In contrast to plasmin, the marked contraction elicited by thrombin ended within 1 hour, and afterward the artery was completely tachyphylactic to thrombin. Fibrin clot, fibrinopeptides, and fibrin degradation products did not prolong significantly the effect of thrombin or prevent the tachyphylaxis. Plasmin and thrombin may occupy a common membrane receptor because exposing the artery briefly to trypsin (24 micrograms/ml) thereafter abolished the contractile effect of plasmin and thrombin without affecting the action of other agonists. Antithrombin III (1.0 unit/ml) relaxed basilar arteries that were precontracted with plasmin (0.5 unit/ml), thrombin (1.0 unit/ml), serotonin (10( 5) M), uridine triphosphate (10(-4) M), or KCl (8 X 10(-2) M). The results suggest that the vasoconstrictor effect of thrombin might contribute to hemostasis after subarachnoid hemorrhage (SAH) but, because of tachyphylaxis, not to delayed vasospasm. On the other hand, the constrictor action of plasmin might appear late in the course of SAH in association with clot lysis and tissue repair. Last, the level of the vasorelaxant antithrombin III in cerebrospinal fluid could control the appearance and severity of cerebral arterial spasm in SAH. PMID- 2579348 TI - Suprasellar germ cell tumor with extracranial metastases. AB - A case of metastasizing suprasellar germ cell tumor is described. Serum tumor markers were measured and the immunochemistry of the tumor was studied. The rarity of extracranial metastasis from suprasellar germinomas is noted, and the relevance to mixed tumors is discussed. The difficulties associated with small biopsies and the importance of tumor marker studies in all cases of an intracranial germ cell tumor are emphasized by the case study. PMID- 2579349 TI - Catecholamine inhibition of calcium action potentials in rat locus coeruleus neurones. AB - Intracellular recordings were made from neurones in the nucleus locus coeruleus in a slice of tissue cut from the rat pons. Clonidine (100 nM-10 microM), noradrenaline (10 microM-1 mM) and adrenaline (10 microM-1 mM) all reduced the duration of the spontaneously occurring action potential of the neurones. This effect was also observed on the action potential in the presence of tetrodotoxin, which results from calcium entering the cell. These concentrations of clonidine, noradrenaline and adrenaline always hyperpolarized the membrane. This hyperpolarization was prevented by two procedures which block potassium currents- intracellular caesium and extracellular barium. In conditions of potassium current blockade, noradrenaline (100 microM-1 mM) and adrenaline (20 microM-1 mM) shortened the calcium action potential but clonidine was ineffective even at 10 microM. Adrenaline and noradrenaline also suppressed inward calcium and barium currents measured under voltage clamp. This action of noradrenaline and adrenaline was not prevented by yohimbine (10 microM), propranolol (20 microM) or prazosin (1 microM); it was reduced by a concentration of phentolamine about 100 times higher than its Ke for alpha 2-adrenoceptors on locus coeruleus neurones. It is concluded that noradrenaline and adrenaline can directly inhibit calcium action potentials in locus coeruleus neurones when applied in high concentrations, but that this does not involve an alpha 2-adrenoceptor. PMID- 2579350 TI - Membrane resistivity estimated for the Purkinje neuron by means of a passive computer model. AB - A multicompartment passive electrotonic computer model is constructed for the cerebellar Purkinje cell of the guinea-pig. The model has 1089 coupled compartments to accurately represent the morphology of the Purkinje cell. In order that the calculated behavior of the model fit the published electrophysiological observations of somatic and dendritic input conductance, the neural membrane resistivity must be spatially non-uniform. The passive electrical parameter values for which the model best fits the observations of input conductances, pulse attenuation and current-clamp voltage transients are rm,dend = 45,740 omega cm2, rm,soma = 760 omega cm2, ri = 225 omega cm and cm = 1.16 microF/cm2 (the membrane and cytoplasm specific resistivities and membrane specific capacitance, respectively). The model with these parameter values is electrically compact, with electrotonic length X = 0.33 and dendritic dominance ratio p = 0.44. Analysis of the calculated voltage transient of the multicompartment model by the methods of equivalent-cylinder cable theory is shown to result in very different and unreliable conclusions. The significance for neuronal function of the estimated electrical parameter values is discussed. The possible effect of active conductances on these conclusions is assessed. PMID- 2579351 TI - Pharmacological and ionic features of gamma-aminobutyric acid receptors influencing electrical properties of melanotrophs isolated from the rat pars intermedia. AB - Characteristics of the gamma-aminobutyric acid receptors on melanotrophs of the rat pars intermedia were studied by intracellular recording. Muscimol and 3-amino 1-propanesulfonic acid, but not baclofen or glycine, mimicked the depolarization and conductance increase produced by gamma-aminobutyric acid on the melanotrophs. These effects appeared to be due to an increase in chloride ion conductance since the null potentials for all three drugs were the same and were affected by changes in external or internal chloride ion concentration but not by changes in the concentrations of other ions present in the recording solution or by the addition of the calcium-channel blocker cobalt. Bicuculline abolished the effect of muscimol. Picrotoxin reduced the effect of gamma-aminobutyric acid; so too did furosemide. Muscimol mimicked the ability of gamma-aminobutyric acid to reduce the depolarization produced by excess potassium and this effect was also blocked by bicuculline. Rat melanotrophs thus appear to possess gamma-aminobutyric acid receptor-ionophore complexes similar to the classical sort found in neurons in the mammalian central nervous system. Furthermore, the parallels between the electrical responses observed and secretory effects previously noted, reinforce the view that electrical activity may participate in stimulus-secretion coupling in melanotrophs. PMID- 2579352 TI - The effects of potassium channel blocking agents on the responses of in vitro frog motoneurones to glutamate and other excitatory amino acids: an intracellular study. AB - Intracellular recordings were obtained from motoneurones of the slice preparation of the in vitro frog spinal cord to assess the participation of K+ channels in the generation of amino acid-induced excitation. The amino acids were applied by fast superfusion and at low temperature to reduce their uptake processes. Intracellular Cs+, bath-applied tetraethylammonium or 4-aminopyridine prolonged the spike and blocked its afterhyperpolarizations. Tetraethylammonium and 4 aminopyridine enhanced the synaptic activation of motoneurones which could be abolished by including Mn2+ in the superfusion fluid. Mn2+ reduced the duration of action potentials already prolonged by 4-aminopyridine but appeared to cause plateaus to develop on tetraethylammonium-prolonged spikes. The hypothesis that amino acids depolarize motoneurones by closing K+ channels was tested by observing the effects of K+ channel blocking agents on amino acid responses. Neither tetraethylammonium nor 4-aminopyridine reduced the excitatory depolarizations evoked by glutamate, N-methyl-D-aspartate, quisqualate or DL homocysteate. Intracellular Cs+ blocked responses to amino acids irrespective of their receptor preference; an action which has been interpreted as non-specific. PMID- 2579353 TI - Kinetics of sodium activation in giant axons of squid (Doryteuthis bleekeri). AB - The variation with time of the rising phase of the sodium conductance in squid giant axons was fitted to the Xth power of running integrals of the colchicine sensitive components of the asymmetry currents, where the running integrals were experimentally obtained. We found that excellent fitting was obtained for all of the potentials examined from -60 to +60 mV, when we put the value of X equal to 3 at potentials above 10 mV and equal to 5 below -20 mV, and it varied continuously from 3 to 5 when pulse potentials changed from 10 to -25 mV. Further, it was found that the voltage dependence of the peak sodium currents was fitted to the third power of charges carried by the colchicine-sensitive component of the asymmetry current by the moment when the sodium current attained its peak. These results agree well with the expectation by Hodgkin and Huxley [(1952) J. Physiol., Lond. 117, 500-544] although the gating kinetics differ from the Hodgkin-Huxley prediction [Matsumoto, Ichikawa and Tasaki (1983) J. Membr. Biol. 77, 93-99]. PMID- 2579354 TI - Characterization of alpha 2-adrenoceptors which increase potassium conductance in rat locus coeruleus neurones. AB - Intracellular recordings were made from locus coeruleus neurones in a slice of rat pons superfused in vitro. A single-electrode voltage-clamp amplifier was used to measure membrane currents. Superfusion of the slice with clonidine (3-100 nM) or noradrenaline (100 nM-100 microM), or brief application of noradrenaline from a pipette by a pressure pulse, caused dose-dependent membrane hyperpolarizations. Phenylephrine (10 microM) and isoprenaline (10 microM) were ineffective. The hyperpolarizations were accompanied by a decrease in neurone input resistance. The hyperpolarization evoked by pressure ejection of noradrenaline could be reversed by membrane polarization to -110 mV. Clonidine and noradrenaline caused a membrane current which was linearly related to membrane potential between -50 and -120 mV, being outward at resting levels and reversing at -110 mV. The concentration-response curves for clonidine and noradrenaline were shifted rightwards in a parallel manner by alpha 2-adrenoceptor antagonists. The antagonist KeS estimated from the degree of shift were: RX 781094 9 nM, yohimbine 14 nM, phentolamine 20 nM and piperoxane 49 nM. These experiments indicate that in locus coeruleus neurones an increase in potassium conductance results from activation of alpha 2-adrenoceptors similar to those characterized on peripheral neurones. PMID- 2579355 TI - CSF immune complexes in multiple sclerosis. AB - Immune complexes from the CSF of 12 individuals (6 with exacerbations of MS and 6 with other neurologic or psychiatric disease) were isolated and characterized. Three MS patients had complexed herpes simplex type I viral antigen and antibody; three patients had complexed myelin basic protein. Two MS patients and one with hypoxic encephalopathy had complexed antibody directed against brain glycolipids. CSF complexes were distinct from serum complexes, suggesting intrathecal origin. Reactivation of latent brain virus may play a role in exacerbations of MS. PMID- 2579356 TI - All or none block of single Na+ channels by tetrodotoxin. AB - The effects of tetrodotoxin on single Na+-channel currents recorded from excised patches of neuroblastoma cells were examined. Tetrodotoxin was found to cause a dose-dependent reduction in the frequency at which Na+ channels conduct during a series of depolarizations. Surviving conducting states had normal open times and current amplitudes. These effects could be explained by a model which includes initial binding of tetrodotoxin to a closed state of the channel with stable, complete block during the time the channel would normally be gated open. PMID- 2579357 TI - Behavioural pharmacology of food, water and salt intake in relation to drug actions at benzodiazepine receptors. AB - Drugs which are agonists at benzodiazepine receptors produce many interesting behavioural effects, and amongst these are the stimulation of food, water and salt intake. This review examines the evidence for benzodiazepine effects on these forms of ingestion, and makes tentative proposals about their modes of action. The recent advent of putative benzodiazepine antagonists and inverse agonists provides important new pharmacological tools for the analysis of factors which control ingestion. Preliminary data on examples of such drugs are considered. Anorectic effects of inverse agonists are described. It is clear, though, that the categorization of a drug in one test situation may not apply to another. For example, the compound Ro15-1788 appears as a specific antagonist in one test, a partial agonist in another, and apparently lacks effect in a third. We are not yet sufficiently forward in our understanding of drug actions at benzodiazepine receptors, and their interactions with particular test circumstances, to predict and account for divergent effects of this kind. PMID- 2579358 TI - Immunologic aspects of gynecologic cancer. PMID- 2579359 TI - Effect of antineoplastic drugs on cell proliferation--individually and in combination. AB - Three antineoplastic agents, bleomycin, cytosine arabinoside and 5-fluorouracil, were studied individually and in combination to determine their effectiveness in controlling cell growth in the presence of fetal bovine serum. All three drugs were effective individually in specifically controlling proliferation (as measured by 3H-thymidine uptake) of human Tenon's capsule fibroblasts while bleomycin is effective at the lowest concentration. However, bleomycin alone rather than in combination with cytosine arabinoside or 5-fluorouracil was most effective in preventing division by these fibroblasts. PMID- 2579361 TI - Comparison between ophthalmoscopy and fundus photography in determining severity of diabetic retinopathy. AB - Diabetic retinopathy was assessed in a population-based study of 2708 diabetic persons in southern Wisconsin. The retinopathy levels as determined by ophthalmoscopy and by the grading of stereoscopic fundus photographs were compared in the eyes of 1949 persons. Ophthalmoscopy was performed by an ophthalmologist and a specially trained optometrist and ophthalmic technician. Consultation among the three examiners was permitted. There was exact agreement between ophthalmoscopy and grading for detecting retinopathy (none, nonproliferative, proliferative) 85.7% of the time. The kappa statistic, which corrects for chance agreement, was 0.749. There were no significant differences among the three ophthalmoscopists. Ophthalmoscopy was more likely to disagree with fundus photography grading in eyes with less severe forms of retinopathy and in patients examined early in the study. Other factors found to influence the degree of agreement were age, visual acuity, and duration of diabetes. It is concluded that with proper training ophthalmoscopy can be an acceptable alternative to fundus photography in certain situations. PMID- 2579360 TI - Experiments on the absorption of argon and krypton laser by blood. AB - Experiments were performed to determine the absorption by and transmission through blood of argon blue-green (ABG) and green (AG) and krypton red (KR) laser light. Krypton was transmitted better through intact erythrocytes than argon. The difference between krypton and argon was greater if the erythrocytes contained oxygenated hemoglobin (Hb) than deoxygenated Hb. None of the wavelengths penetrated well a confluent blood specimen only 4 cells thick. Branch retinal vein occlusions were created in monkeys causing scattered areas of retinal hemorrhage. Argon burns placed in areas of retinal hemorrhage caused much inner or full thickness retinal damage. Krypton passed through the inner retinal hemorrhage without causing damage and created a burn at the level of the retinal pigment epithelium and inner choroid. Preretinal hemorrhages were created in rabbits by perforating Bruch's membrane with a high intensity krypton burn. Argon burns placed over the preretinal hemorrhages were absorbed much more than krypton burns. Neither argon or krypton however could penetrate even moderately thick preretinal hemorrhages to cause an underlying retinal burn. PMID- 2579362 TI - Verrucous carcinoma: a possible viral pathogenesis. AB - Seventeen cases of verrucous carcinoma of the oral cavity were reviewed. It was found that cytologic features generally associated with viral modification were observed in 15 of these cases. This finding suggests that viruses may play some role in the pathogenesis of verrucous carcinoma. The hypothesis that an opportunistic, persistent virus may act in concert with frank carcinogens to promote the development of verrucous carcinoma is discussed. PMID- 2579363 TI - Distribution of keratin proteins in neoplastic and tumorlike lesions of squamous epithelium. An immunohistochemical study. AB - Seventy-six cases of tumorlike and neoplastic lesions from epidermis and oral epithelium were analyzed by a histochemical technique for the demonstration of keratin. Formalin-fixed paraffin sections were reacted with rabbit antihuman keratin antiserum (dilution of 1:40). The types of distribution of keratin in cells of lesions were classified into five categories: (1) regional, as found in normal squamous epithelia and benign hyperkeratinized lesions, and papilloma, and keratinized squamous cell carcinoma; (2) total, as seen in intensely keratinized lesions, such as verruca vulgaris and highly keratinized squamous cell carcinoma; (3) negative, as displayed by basal cell carcinoma; (4) scattered, as in the most poorly differentiated squamous cell carcinomas; and (5) mixed cellular, as found in both poorly and moderately differentiated squamous cell carcinomas. PMID- 2579364 TI - First-year developmental outcomes for multiple-risk premature infants. PMID- 2579366 TI - Patient education and pediatric oncology. AB - An overview is provided of important principles and content useful in planning educational programs for pediatric oncology patients and their families. Implementation considerations, such as assessment of the learner, selection of appropriate teaching methods, and problems with the selection process are addressed. PMID- 2579365 TI - Cerebrospinal fluid neurotransmitter metabolites in neurologically normal infants and children. AB - Significant inverse correlations with age were observed for free 3-methoxy-4 hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) concentrations in CSF from 75 neurologically normal newborns, infants, and children aged 1 day to 10 years. The concentration of free MHPG decreased rapidly in early neonatal life and was reduced to near adult levels by 8 to 9 months of age. Adult levels of 5-HIAA were observed at about 4 years of age whereas HVA concentrations were still above adult levels at 10 years of age. Data from 0- to 1-month-old premature (28 to 32 weeks of gestation) and full-term (37 weeks of gestation) infants revealed marked changes in HVA and 5-HIAA concentrations which were related to postconceptional rather than postnatal age. This study demonstrates a previously undetected age effect on CSF MHPG concentration during the neonatal period and provides valuable normal data that are necessary for the interpretation of CSF monoamine metabolites in infants and children with hyperphenylalaninemia and other neurologic disease involving monoamine neurotransmitters. PMID- 2579368 TI - [Results of treatment of herpes simplex and herpes zoster with isoprinosine]. PMID- 2579367 TI - [Selected biochemical indicators of fetal risk in cases of Rh(D) isoimmunization]. PMID- 2579370 TI - Zinc and cadmium concentrations in whole tissue and in separated epithelium and stroma from human benign prostatic hypertrophic glands. AB - Prostate tissues from patients with benign prostatic hypertrophy were separated into epithelial and stromal components and the concentrations of zinc and cadmium were determined in these two fractions and in whole tissue by atomic absorption spectrophotometry. The concentrations of testosterone and 5 alpha dihydrotestosterone (5 alpha-DHT) were determined by radioimmunoassays. The concentration of zinc was found to be significantly greater (P less than .001) in epithelial than in stromal preparations: 17.32 +/- 1.15 vs. 7.29 +/- 0.53 mumol/g dry weight (SEM, n = 15). The concentrations of cadmium in epithelium, 9.55 +/- 1.31 nmol/g dry weight (SEM, n = 15) and in stroma, 6.65 +/- 1.06 nmol/g dry weight (SEM, n = 15), did not differ significantly. The concentrations of zinc and cadmium in whole tissues were 13.88 +/- 1.70 mumol/g dry weight and 8.85 +/- 1.53 nmol/g dry weight, respectively (SEM, n = 15). In epithelial preparations, cadmium and testosterone were inversely correlated, but no other correlations were noted between metal and androgen concentrations in whole tissue, stroma, or epithelium. The results of the present study indicate that zinc preferably resides in the epithelium of human prostatic tissue, particularly in BPH, although the stroma also contains significant amounts of this metal. Cadmium appears to be more evenly distributed between the epithelium and stroma of prostatic tissue and previous findings of high cadmium concentrations in hypertrophic and carcinomatous prostatic tissue were not confirmed. PMID- 2579369 TI - The effect of prolactin on human BPH epithelial cell proliferation. AB - Epithelial cell monolayers derived from specimens of human benign prostatic hyperplasia (BPH) tissue by an explant culture technique were cultured with prolactin in the presence and absence of androgens. Proliferation of the cells was measured by both autoradiographic assessment of [3H]-thymidine uptake and stathmokinetic procedures. Prolactin significantly stimulated the growth of these cells in the concentration range 0.5 mIU/ml to 10 mIU/ml but was inhibitory at a concentration of 100 mIU/ml. In the presence of testosterone (1 X 10(-7) M), prolactin at low concentrations (greater than 1 mIU/ml) but not at 10 mIU/ml, the concentration at which all other experiments were performed, produced a further stimulation in the proliferation. The increase in growth seen with cells cultured with 5 alpha-dihydrotestosterone (1 X 10(-7) M) was reduced with addition of prolactin at high concentrations (10-100 mIU). When the fetal calf serum used in the cultures was stripped of endogenous steroids, prolactin still increased cell proliferation, although to a reduced extent. This indicated that the effects of prolactin were not dependent on the presence of androgens. PMID- 2579371 TI - Nuclear androgen receptor content in biopsy specimens from histologically normal, hyperplastic, and cancerous human prostatic tissue. AB - Androgen receptors (ARn) were assayed in nuclear extracts of prostatic biopsies from 60 patients with benign prostatic hyperplasia (BPH) and 82 patients with prostatic cancer (PC), with an exchange assay using heparin extraction, labelling with 3H-R1881, and protamine sulphate precipitation. The content of ARn of BPH biopsies (38 +/- 34 fmol/mg protein [mean +/- SD]; n = 70) was not different from that of PC biopsies (39 +/- 32 fmol/mg protein; n = 115). Biopsies showing essentially normal prostatic tissue had a lower ARn content (12 +/- 13 fmol/mg protein; n = 6). The content of ARn was independent of the age of the patient and of the histological grade of the carcinomas. A considerable variation in ARn content within tumors of individual patients was found, indicating that ARn are not uniformly distributed over prostatic tissue; ie, cells with high and low receptor content may coexist in different proportions in different regions of the prostate. Therefore, assays on multiple biopsies may be required for a proper estimation of the mean receptor content. The question remains, however, whether the behavior of the tumor is adequately predicted by the mean receptor level or, for instance, by the region with the lowest receptor content. PMID- 2579372 TI - Is this child developing properly? A practical tool for monitoring. AB - The developmental picture of a child can be appreciated only by regular comparison of the child's progress with normal milestones for age in an organized and systematic manner. The Kansas Infant Development Screen (KIDS) chart is a useful instrument for this very important element of well-child visits. It is simple to use and easily interpreted by health care providers and parents. PMID- 2579373 TI - Avian pox: infection and immunity with quail, psittacine, fowl, and pigeon pox viruses. AB - Quail, chickens, and turkeys vaccinated with pigeon and fowl pox viruses were not protected against challenge of their immunity with quail pox virus and they developed severe cutaneous lesions of pox. When quail and chickens were vaccinated with quail pox virus and given pigeon and fowl pox challenge viruses, no protection was present. Thus, quail pox virus had no immunologic relationship to pigeon and fowl pox viruses. Psittacine pox virus applied as a vaccine in quail and chickens also failed to protect against quail pox virus challenge. However, quail, chickens, and turkeys vaccinated with quail pox virus were protected against quail pox virus challenge. An isolate of psittacine pox virus, applied as a vaccine, protected chickens against challenge with the same virus isolate and also against challenge with two other psittacine pox virus isolates, confirming a close or identical antigenic relationship with each other. When combined in a multivalent vaccine, quail, psittacine, and fowl pox viruses induced excellent protection in chickens against challenge with the three respective viruses. The presence or absence of "takes" or reactions following vaccination by the wing web route did not necessarily correlate with the presence or absence of immunity noted from challenge by feather follicle virus application. The role of quail and psittacine pox viruses as potential pathogens for poultry was discussed briefly. PMID- 2579374 TI - The impact of maternal serum alpha fetoprotein screening on open neural tube defect births in north-east Scotland. AB - Over the three years period 1980-1982, 18 256 pregnancies in the Grampian Region of N-E Scotland including the islands of Orkney and Shetland were screened for raised levels of maternal serum alpha fetoprotein (MSAFP) in the second trimester. Thirty six cases of fetal open neural tube defect in singletons were detected (18 anencephaly and 18 spina bifida). Four additional cases of open spina bifida were associated with normal MSAFP levels although two of these were detected by amniotic fluid AFP measurement when amniocentesis was carried out because of previous NTD history. A further three cases of open spina bifida and two of anencephaly occurred in unscreened pregnancies. The MSAFP screening programme alone was thus instrumental in reducing the birth incidence of open neural tube defects by 36 out of 45 cases (80 per cent) in singletons. PMID- 2579375 TI - Maternal serum alpha-fetoprotein screening for neural tube defects. Results of a consensus meeting. PMID- 2579376 TI - Tests appropriate for the prenatal diagnosis of ataxia telangiectasia. AB - A fetus 'at-risk' for ataxia telangiectasia (A-T) was monitored prenatally by several approaches which, in concert, might yield information of diagnostic value: measurement of amniotic fluid AFP levels; the clastogenic potential of 'at risk' amniotic fluid; and cytogenic evaluation of fetal amniocytes. All three parameters proved negative and normality, based primarily on the chromosomal study of fetal cells, was therefore presumed. This conclusion was confirmed shortly after birth by normal serum AFP levels and the lack of increased spontaneous or clastogen-induced chromosome breakage in the infant's cells. Based on previous observations from four normal and one affected fetus, the coordination of these techniques provides adequate methodology for the antenatal assessment of the phenotypes associated with A-T. PMID- 2579377 TI - Plasmid pT181 replication is regulated by two countertranscripts. AB - A transcription map of the replication control region of the Staphylococcus aureus plasmid pT181 has been constructed. Two major leftward transcripts, RNA III and RNA IV, start at positions 339 and 413, respectively. These two RNAs can serve as mRNAs for a plasmid-specific replication protein RepC. Two short rightward transcripts, RNA I and RNA II, approximately 85 and 150 nucleotides long, respectively, start at position 246. These rightward transcripts (referred to as countertranscripts) do not appear to be translated but act directly as negative regulators of plasmid replication, probably by interfering with translation of the RepC mRNAs. There is no significant base sequence homology among the countertranscripts of pT181, ColE1, and R1/NR1/R6-5, suggesting that the structural parallelism has risen by convergent molecular evolution. PMID- 2579378 TI - Secondary structure of the circular form of the Tetrahymena rRNA intervening sequence: a technique for RNA structure analysis using chemical probes and reverse transcriptase. AB - The structure of the intervening sequence (IVS) of the Tetrahymena rRNA precursor mediates cleavage-ligation reactions that result in pre-rRNA splicing and IVS cyclization. We have developed a method for RNA structure analysis and applied it to the circular form of the IVS RNA. The native RNA was treated with dimethyl sulfate or diethyl pyrocarbonate to modify bases not involved in secondary or tertiary interactions. The RNA was then used as a template for reverse transcription. Elongation of synthetic oligodeoxynucleotide primers was found to stop (or pause) one nucleotide prior to 1-methyladenosine, 3-methylcytidine, and 7-ethoxycarbonyladenosine residues. The detection of 1-methyladenosine is particularly useful for locating single-stranded regions. After chemical cleavage of the RNA, 7-methylguanosine also could be detected. In general, the sites of modification were consistent with a previous model of the secondary structure of the linear form of the IVS RNA, a model based on enzymatic cleavage data, free energy calculations, and phylogenetic comparison. Thus, IVS RNA autocyclization does not involve major rearrangements of the secondary structure, although there is evidence for a conformational change in one region of the molecule. The methods described here should be of general use for obtaining information about structure far from the ends of RNA molecules. PMID- 2579379 TI - Human complement component C3: cDNA coding sequence and derived primary structure. AB - The complete cDNA coding sequence and derived amino acid sequence of human complement component C3 are presented. The encoded precursor molecule contains a signal peptide of 22 amino acid residues, the beta chain (645 residues), and the alpha chain (992 residues). The two chains are joined by four arginine residues not present in the mature protein. Several functionally important sites have been localized, such as the thiolester site, the cleavage site liberating the anaphylatoxin, and two sites of cleavage by the serine protease factor I, as well as a peptide fragment with leukocyte mobilizing activity. At least two carbohydrate attachment sites, one on each chain, have been identified. Human C3 has 79% identity to mouse C3 at the nucleotide level and 77% identity at the amino acid level. The protease alpha 2-macroglobulin and complement component C4 show considerable homology to C3, suggesting that the three proteins have evolved from a common ancestor. PMID- 2579380 TI - Adult and fetal human globin genes are expressed following chromosomal transfer into MEL cells. AB - Somatic cell hybridization of mouse erythroleukemia (MEL) cells and HEL cells, a human erythroleukemia line that produces fetal (gamma) but fails to express adult (beta) globin, was used to test whether the expression of the two human globin genes is regulated cis or trans. An experimental approach using anti-human globin monoclonal antibodies for detection, efficient cloning, and monitoring of hybrids of interest was employed. Further characterization of hybrids used isoelectric focusing for detection of human globins and S1 nuclease mapping. In contrast to the parental HEL line, all chromosome 11-retaining HEL-MEL hybrids expressed human beta-globin, suggesting that the HEL beta-globin genes (i) are transcriptionally competent, (ii) become activated in response to a positive trans-acting element within the MEL environment, and (iii) fail to express into the HEL environment because of either the absence of a positive trans-acting element or the presence of a trans-acting inhibitor of beta-globin gene expression. In addition to beta-globin, the primary HEL-MEL hybrids co-expressed gamma-globin; however, gamma-globin expression segregated by subcloning so that secondary and tertiary clones either expressed only beta-globin or co-expressed gamma- and beta-globin. The results of subcloning can be explained by assuming that gamma-globin gene expression is controlled by a HEL cell-derived transacting element encoded by a gene not syntenic to chromosome 11 or by postulating that the HEL gamma-globin genes become randomly modified during the continuous proliferation of hybrids. PMID- 2579381 TI - Cardiac dysfunction caused by purified human C3a anaphylatoxin. AB - The purpose of this investigation was to define the cardiac effects of complement derived C3a anaphylatoxin, in view of the possibility that cardiac dysfunction may occur as a result of complement activation. Purified human C3a was administered by intracoronary bolus injections into isolated guinea pig hearts. As a function of dose, C3a caused tachycardia, impairment of atrioventricular conduction, left ventricular contractile failure, coronary vasoconstriction, and histamine release. These effects were abolished by cleavage of the COOH-terminal arginine by carboxypeptidase B. The magnitude of C3a-induced tachycardia correlated with the amount of endogenous cardiac histamine released into the coronary effluent. Whereas the tachycardia was markedly reduced by the histamine H2 antagonist cimetidine, the contractile failure and the coronary vasoconstriction caused by C3a were antagonized by the leukotriene antagonist FPL 55712 and by the cyclooxygenase inhibitor indomethacin, respectively. This suggests that histamine, leukotrienes, and vasoactive prostanoates may mediate the various cardiac effects of C3a. Our findings indicate that C3a anaphylatoxin has marked cardiac effects at concentrations that are likely to be attained with a degree of C3 activation commonly seen in various disease states. Thus, our data are compatible with the hypothesis that generation of anaphylatoxins may induce cardiac dysfunction in clinical conditions. PMID- 2579382 TI - Giant axonal neuropathy: acceleration of neurofilament transport in optic axons. AB - Giant axonal neuropathies are a group of acquired and inherited human diseases morphologically characterized by accumulation of neurofilaments (NF) in enlargements of preterminal regions of central and peripheral axons. Slow axonal transport was studied in the optic systems of rats treated with 2,5-hexanedione, a toxic compound that produces an experimental model of giant axonal neuropathy. The transport rate of NF and of two other polypeptides of Mr 64,000 and 62,000 were selectively increased. Other components of the slow axonal transport were not affected. Acceleration of labeled NF was also observed when 2,5-hexanedione was given after [35S]methionine administration. Morphometric analysis revealed that the number of NF and the axon size were decreased in regions of optic axons proximal to the enlargements. It is suggested that acceleration of NF transport leads to a longitudinal redistribution of NF: NF decrease proximally and increase distally, forming NF-containing enlargements. Evidence was obtained that polypeptides of Mr 64,000 and 62,000 are cytoskeletal components related to intermediate filaments, normally migrating with the component a of the slow axonal transport. The 2,5-hexanedione axon may provide insight into the pathogenesis of inherited and acquired giant axonal neuropathies and offers a model to investigate the relationship between number of NF and axonal size in central axons. PMID- 2579384 TI - Voltage-dependent sodium and potassium channels in mammalian cultured Schwann cells. AB - Cultured Schwann cells from sciatic nerves of newborn rabbits and rats have been examined with patch-clamp techniques. In rabbit cells, single sodium and potassium channels have been detected with single channel conductances of 20 pS and 19 pS, respectively. Single sodium channels have a reversal potential within 15 mV of ENa, are blocked by tetrodotoxin, and have rapid and voltage-independent inactivation kinetics. Single potassium channels show current reversal close to EK and are blocked by 4-aminopyridine. From these results, and from comparisons of single-channel and whole-cell data, we show that these Schwann cells contain voltage-dependent sodium and potassium channels that are similar in most respects to the corresponding channels in mammalian axonal membranes. Cultured rat Schwann cells also have sodium channels, but at a density about 1/10th that of rabbit cells, a result in agreement with saxitoxin binding experiments on axon-free sectioned nerves. Saxitoxin binding to cultured cells suggests that there are up to 25,000 sodium channels in a single rabbit Schwann cell. We speculate that in vivo Schwann cells in myelinated axons might act as a local source for sodium channels at the nodal axolemma. PMID- 2579383 TI - Evidence for widespread effects of noradrenaline on axon terminals in the rat frontal cortex. AB - Noradrenaline, apparently working through activation of beta-adrenergic receptors, alters the state of phosphorylation of a substantial proportion of synapsin I in rat frontal cortex. Since synapsin I is enriched in virtually all axon terminals in this brain region, the results indicate that noradrenaline, a sparsely distributed neurotransmitter, affects a large number of axon terminals in this region. The results also suggest that noradrenaline receptors are present on a substantial percentage of all axon terminals in the cerebral cortex, despite the low density of noradrenergic fibers present. The data support the view that noradrenaline may serve a paracrine function. PMID- 2579385 TI - 23Na and 39K NMR studies of ion transport in human erythrocytes. AB - Ion transport in human erythrocytes was studied by 23Na and 39K NMR with an anionic paramagnetic shift reagent, Dy(P3O10)2(7-). The intra- and extracellular 23Na and 39K NMR signals were well separated (over 10 ppm) at 5 mM concentration of the shift reagent. The NMR visibility of the intracellular Na+ and K+ was determined to be 100% in human and duck erythrocytes. The intracellular ion concentrations were 8.1 +/- 0.8 mM Na+ (n = 7) and 110 +/- 12 mM K+ (n = 4) for fresh human erythrocytes. The ouabain-sensitive net Na+ efflux was 1.75 +/- 0.08 mmol/hr per liter of cells at 37 degrees C (n = 3). The gramicidin-induced ion transport in human erythrocytes was also studied by 23Na and 39K NMR or by simultaneous measurements of 23Na NMR and a K+-selective electrode. The time courses of the Na+ and K+ transport induced by the ionophore were biphasic. The initial rapid fluxes were due to an exchange of Na+ for K+, which were found to occur with a 1:1 stoichiometry. The subsequent slow components were the net Na+ and K+ effluxes rate-limited by the Cl- permeability and accompanied by a reduction in cell volume. The Cl- permeability determined from the NMR measurements of these slow fluxes was 3.2 +/- 0.5 X 10(-8) cm/sec at 25 degrees C (n = 4). PMID- 2579386 TI - Calcium currents in GH3 cultured pituitary cells under whole-cell voltage-clamp: inhibition by voltage-dependent potassium currents. AB - To isolate inward Ca2+ currents in GH3 rat pituitary cells, an inward Na+ current as well as two outward K+ currents, a transient voltage-dependent current (IKV) and a slowly rising Ca2+-activated current (IKCa), must be suppressed. Blockage of these outward currents, usually achieved by replacement of intracellular K+ with Cs+, reveals sustained inward currents. Selective blockage of either K+ current can be accomplished in the presence of intracellular K+ by use of quaternary ammonium ions. When IKCa and Na+ currents are blocked, the net current elicited by stepping the membrane potential (Vm) from -60 to 0 mV is inward first, becomes outward and peaks in 10-30 msec, and finally becomes inward again. Under this condition, in which both IKV and Ca2+ currents should be present throughout the duration of the voltage step, the Ca2+ current was not detected at the time of peak outward current. That is, plots of peak outward current vs. Vm are monotonic and are not modified by nisoldipine or low external Ca2+ as would be expected if Ca2+ currents were present. However, similar plots at times other than at peak current are not monotonic and are altered by nisoldipine or low Ca2+ (i.e., inward currents decrease and plots become monotonic). When K+ channels are first inactivated by holding Vm at -30 mV, a sustained Ca2+ current is always observed upon stepping Vm to 0 mV. Furthermore, substitution of Ba2+ for Ca2+ causes blockage of IKV and inhibition of this current results in inward Ba2+ currents with square wave kinetics. These data indicate that the Ca2+ current is completely inhibited at peak outward IKV and that Ca2+ conductance is progressively disinhibited as the transient K+ current declines due to channel inactivation. This suggests that in GH3 cells Ca2+ channels are regulated by IKV. PMID- 2579387 TI - One gene and one pseudogene for the cytokeratin endo A. AB - The recombinant cDNA RecXVI, which hybridizes to the endo A mRNA, detects two specific bands on a Southern blot of EcoRI-digested genomic mouse DNA. We have screened a mouse genomic library with this cDNA and isolated these two sequences. Endo A is encoded by a 7.5-kilobase gene and by a 1.6-kilobase pseudogene devoid of introns. A repetitive sequence belonging to the B2 family is located in the third intron of the gene. We have observed that transcription of B2 sequences and of the endo A gene are mutually exclusive. PMID- 2579388 TI - Construction of the mycoplasma evolutionary tree from 5S rRNA sequence data. AB - The 5S rRNA sequences of eubacteria and mycoplasmas have been analyzed and a phylogenetic tree constructed. We determined the sequences of 5S rRNA from Clostridium innocuum, Acholeplasma laidlawii, Acholeplasma modicum, Anaeroplasma bactoclasticum, Anaeroplasma abactoclasticum, Ureaplasma urealyticum, Mycoplasma mycoides mycoides, Mycoplasma pneumoniae, and Mycoplasma gallisepticum. Analysis of these and published sequences shows that mycoplasmas form a coherent phylogenetic group that, with C. innocuum, arose as a branch of the low G+C Gram positive tree, near the lactobacilli and streptococci. The initial event in mycoplasma phylogeny was formation of the Acholeplasma branch; hence, loss of cell wall probably occurred at the time of genome reduction to approximately to 1000 MDa. A subsequent branch produced the Spiroplasma. This branch appears to have been the origin of sterol-requiring mycoplasmas. During development of the Spiroplasma branch there were several independent genome reductions, each to approximately 500 MDa, resulting in Mycoplasma and Ureaplasma species. Mycoplasmas, particularly species with the smallest genomes, have high mutation rates, suggesting that they are in a state of rapid evolution. PMID- 2579389 TI - Isolation of cDNA clones coding for the beta subunit of human beta hexosaminidase. AB - The major forms of beta-hexosaminidase (2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase, EC 3.2.1.30) occur as multimers of alpha and beta chains--hexosaminidase A (alpha beta a beta b) and hexosaminidase B 2(beta a beta b). To facilitate the investigation of beta-chain biosynthesis and the nature of mutation in Sandhoff disease, a human hexosaminidase beta-chain cDNA clone was isolated. Hexosaminidase B (10 mg) was treated with CNBr, five peptide fragments were isolated by reverse-phase HPLC, and their amino acid sequences were determined. One of these contained a string of six amino acids from which an oligonucleotide probe was defined. The simian virus 40-transformed human fibroblast cDNA library of Okayama and Berg was screened by colony hybridization with the radiolabeled probe. Thirteen probe-binding clones were selected out of 50,000 clones screened. Four of these designated pHex were shown to be identical at their 3' ends by restriction enzyme mapping, differing only in their 5' extensions (1.4-1.7 kilobases). The nucleotide sequence of a 174-base-pair segment contained the deduced amino acid sequence of two of the five CNBr peptides, indicating that the pHex clones encode the beta subunit of hexosaminidase. In addition, pHex cDNA was found homologous to multiple bands in digests of genomic human DNA totaling 43 kilobases (kb), all of which were mapped to chromosome 5 in somatic cell hybrids, as expected of the HEXB gene. The pHex cDNA also hybridized to a 2.2-kilobase RNA that apparently codes for the pre-beta polypeptide of hexosaminidase. This RNA species was absent in the fibroblasts of one of three patients with Sandhoff disease examined. We anticipate that these clones will be of value to diagnosis and carrier detection of Sandhoff disease in affected families. PMID- 2579390 TI - Repetitive A epitope (type 3 chain A) defined by blood group A1-specific monoclonal antibody TH-1: chemical basis of qualitative A1 and A2 distinction. AB - The IgG2a monoclonal antibody TH-1, which reacts specifically with blood group A1 but with neither A2 nor O erythrocytes, has been established. The antibody reacted only with A1 erythrocytes in hemagglutination and antibody absorption assays; it did not react with A2 erythrocytes, even after trypsin or sialidase treatment. This antibody detected, on TLC immunostaining, a series of glycolipids from A1 erythrocytes but virtually none or very weak bands from A2 erythrocytes. It did not react with type 1 or type 2 chain A, or with globo-A. The simplest reactive component was isolated from a previously assigned Ab fraction by HPTLC of acetylated compounds. The structure of the reactive component was characterized by 1H NMR spectroscopy, methylation analysis, and enzymatic degradation, as shown below: (Formula: see text). The structure is essentially a repetitive A epitope attached to type 2 chain and is hereby called type 3 chain A. The determinant can be carried on extended and/or branched structures, but it was not detectable in glycoproteins. The structure was characteristic of A1 erythrocytes and present in only trace amounts in A2 erythrocytes. The precursor H (Fuc alpha 1----2Gal beta 1----3GalNAc alpha 1----3[Fuc alpha 1----2]Gal beta 1 ---4GlcNAc beta 1----R; type 3 chain H) was present in greater quantity in A2 erythrocytes than in A1 erythrocytes, but it was absent in both O and B erythrocytes. The A1 transferase apparently can transfer alpha-GalNAc to type 3 chain H, while the A2 transferase may not have this ability. PMID- 2579391 TI - Bioeffective monoclonal antibody against the decapeptide gonadotropin-releasing hormone: reacting determinant and action on ovulation and estrus suppression. AB - A monoclonal antibody generated against the decapeptide gonadotropin-releasing hormone (GnRH) was effective in intercepting the bioactivity of the hormone; it blocked ovulation in rats. The antibody reacted optimally with the native hormone. Substitution of amide at the COOH terminus by a carboxyl group decreased immunoreactivity by a factor of 200. The antibody recognized the amino acid sequences 4-6, 7-10, and 4-10 to a variable degree, which suggests that the epitope has a conformation involving the entire molecule, with the NH2- and COOH terminal regions probably in proximity. The antibody was also competent to suppress the progression of estrus in dogs, an indication that GnRH may play an inductive role in the reproductive function of dogs. PMID- 2579392 TI - Neuroleptic drugs attenuate calcium influx and tension development in rabbit thoracic aorta: effects of pimozide, penfluridol, chlorpromazine, and haloperidol. AB - This study was designed to determine whether neuroleptic drugs have calcium channel blocking activity in isolated rings of rabbit thoracic aorta. The results confirm previous findings that pimozide and penfluridol are calcium channel blockers. However, the data do not support the conclusion that these agents are selective for the voltage-sensitive calcium channel. The results also show that both haloperidol and chlorpromazine (which represent different classes of neuroleptic drugs) are also calcium channel blockers in vascular smooth muscle. PMID- 2579393 TI - Interaction of synaptic modification rules within populations of neurons. AB - A theoretical account is given for long- and short-term changes in populations of neurons subject to independent rules for pre- and postsynaptic modification. The postsynaptic rule proposes that coactivated heterosynaptic inputs to a neuron alter the states of ion channels at a given synapse, thereby changing the susceptibility of these channels to local biochemical alterations. The resultant change in the population distribution of local channel states affects the postsynaptic potential produced at the synapse by subsequent inputs. This postsynaptic rule applies, in general, to short-term changes at specific individual synapses. In contrast, the presynaptic rule applies in general to long term changes in the whole neuron, resulting in an altered probability of transmitter release. Because of neuroanatomical constraints, the presynaptic rule affects large numbers of synapses defined by the connectivity of that neuron and distributed nonspecifically over the population. We show that the combined action of the two independent rules upon populations of neurons arrayed in interconnected neuronal groups leads to consistent alterations of the probability of firing of certain circuits while maintaining variability in the response of the population to novel input. This "dual rules" model fulfills the requirements of the theory of neuronal group selection. PMID- 2579395 TI - Cyclization of RNA 3'-terminal phosphate by cyclase from HeLa cells proceeds via formation of N(3')pp(5')A activated intermediate. AB - RNA 3'-terminal phosphate cyclase has been partially purified from HeLa cells. In the presence of ATP and Mg2+, cyclase preparations catalyze conversion of RNA 3' terminal phosphate to the 2',3'-cyclic phosphodiester. The mechanism of 3' phosphate cyclization was studied with oligoribonucleotides containing terminal 2'-deoxy- or 2'-O-methylribose. Incubation of these substrates with cyclase and ATP results in formation of the corresponding activated 3'-terminal structures, dN(3')pp(5')A and Nm(3')pp(5')A. It is proposed that an intermediate step in cyclization is transfer of the adenylyl group from ATP to the 3' phosphate of RNA. Rapid attack of the adjacent 2'-OH normally follows, resulting in elimination of AMP and formation of the cyclic phosphodiester. Cyclase preparations can be covalently labeled with [alpha-32P]ATP, suggesting that an earlier step in the cyclization reaction involves formation of an adenylylated enzyme intermediate. PMID- 2579394 TI - Scrapie and Creutzfeldt-Jakob disease prion proteins share physical properties and antigenic determinants. AB - Scrapie of sheep and goats as well as Creutzfeldt-Jakob disease (CJD) of humans are neurologic disorders caused by slow infectious pathogens. The novel molecular properties of the pathogen causing scrapie have prompted introduction of the term "prion" to denote a small proteinaceous infectious particle that resists inactivation by nucleic acid-modifying procedures. Antiserum to the major hamster scrapie prion protein (PrP 27-30) was found to cross-react with murine CJD proteins. The CJD proteins had molecular weights similar to those observed for scrapie prion proteins as determined by NaDodSO4 gel electrophoresis. In addition, the CJD proteins were resistant to digestion by proteinase K and appear to polymerize into rod-shaped particles. The purification procedure developed for scrapie prions was found to be useful in purifying the CJD agent. Purification of the two infectious pathogens by virtually identical procedures provided further evidence for similarities in their molecular structures. We conclude that the molecular and biologic properties of the CJD agent are sufficiently similar to those of the scrapie prion protein that CJD should be classified as a prion disease. PMID- 2579396 TI - Acidic pH requirement for insertion of colicin E1 into artificial membrane vesicles: relevance to the mechanism of action of colicins and certain toxins. AB - The channel-forming activity of colicin E1 in artificial membranes is known to increase at low pH values and to have a maximum near pH 4 in such membrane vesicles. The present work demonstrates that this pH dependence of activity can be attributed to membrane binding. Maximal binding of colicin E1 and a more slowly binding channel-forming carboxyl-terminal tryptic peptide occurred at acidic pH values, with the effective pK values for binding equal to 4.6 and less than 4.0, respectively. The binding did not require imposition of a transmembrane potential. Insertion of the tryptic peptide into the membrane was shown by retention of bound [3H]leucine-labeled peptide by vesicles after digestion with protease, as well as by retention of the peptide in salt-washed vesicles. The retention after protease treatment was also used to estimate the amount of carboxyl-terminal peptide inserted into the membrane. Approximately 12 of the 21 leucines present in the carboxyl-terminal peptide were retained after Pronase treatment at pH less than 4. Reversibility of the insertion at low pH values was seen after an alkaline shift of pH to 6.0, resulting in a decrease of the protease-inaccessible fraction of the bound protein. A model is presented describing a mechanism in which protonation of one or more carboxyl residues is necessary for effective binding and insertion into the membrane by the channel forming domain of colicin E1. This model may also be relevant to the mechanism of membrane insertion by certain toxins. PMID- 2579398 TI - Analysis of an evolutionarily conserved antigenic site on mammalian cytochrome c using synthetic peptides. AB - Two synthetic peptides inclusive of the NH2-terminal N-acetyl-Gly-Asp-Val-Glu tetrapeptide of mammalian cytochrome c (cyt c) were used in this study to address the question of whether mammals can respond immunologically to an evolutionarily conserved region of a protein. These peptides were assessed for their capacity (i) to act as immunogens for the production of anti-self cyt c antisera and (ii) to bind rabbit anti-rodent cyt c antibody. The findings from these studies indicate the existence of an immunogenic determinant in an evolutionarily conserved region of cyt c that contains residues 1-4. This determinant can induce anti-self cyt c antibodies whether presented as a peptide on a carrier protein or in the context of the intact molecule as polymerized mammalian cyt c. PMID- 2579397 TI - Treatment of mice with 5-azacytidine efficiently activates silent retroviral genomes in different tissues. AB - The drug 5-azacytidine was injected into mice to activate silent retroviral genomes. The Mov-7 and Mov-10 substrains of mice were used, each of which carries a Moloney murine leukemia provirus with mutations in the coding regions at nonidentical positions. These proviral genomes are highly methylated and are not expressed in the animal. A single injection of the drug into postnatal mice induced transcription of the endogenous defective proviral genomes in thymus, spleen, and liver at 3 days after treatment. No viral transcription was detected in the brain of drug-exposed animals. When postnatal Mov-7/Mov-10 F1 mice were treated with the drug, infectious virus was generated efficiently and resulted in virus spread and viremia in all animals by 3 weeks of age. In contrast, infectious virus was not generated in F1 mice that had been treated during gestation with up to sublethal doses of the drug. Our results demonstrate that injection of 5-azacytidine can be used to efficiently and reproducibly activate silent genes in different cell populations of postnatal mice. PMID- 2579399 TI - The monoaminergic innervation of the rat visual cortex. AB - The intracortical distribution of monoamines, noradrenaline (NA) and serotonin (5 HT), was examined in the visual cortex of the rat with high pressure liquid chromatography (h.p.l.c.) and radioautography. H.p.l.c. measurements showed the densities of both amines to be highest in layer I. The concentration of NA varied considerably in all other layers while the 5-HT concentration decreased with increasing distance from the pial surface. The morphological characteristics of the monoaminergic axon-terminals in the cerebral cortex has been the subject of controversy in recent years. We have used radioautography following topical or intraventricular administration of tritiated amines to examine the ultrastructural features of these terminals in the visual cortex of the rat. Systematic analysis of single sections revealed that more than one-half of the terminals labelled with tritiated NA or 5-HT formed typical synaptic contacts (mostly type I) with dendritic shafts or spines. PMID- 2579400 TI - Kinetics of light-sensitive channels in vertebrate photoreceptors. AB - We have studied the ion channels mediating the light response of vertebrate rod photoreceptors by analysing fluctuations in the current across the rod membrane, using the whole cell patch-clamp technique on rods isolated from the axolotl retina. Light decreases the membrane current fluctuations. Noise analysis reveals two components to this decrease: a low frequency component due to biochemical noise in the transduction mechanism, and a high frequency component we attribute to the random opening and closing of the ion channels in the dark. The probability of any one channel being open in the dark is low. The spectrum of the high frequency component of the current fluctuations indicates that the current through an open channel is 4 X 10(-15)A, that the mean channel open time is 2 ms, and that about 10000 channels are open in each rod in the dark. The effect of light is to reduce the opening rate constant of these channels, with no effect on the closing rate constant. PMID- 2579401 TI - beta-Adrenergic induced K+ current in Xenopus oocytes: role of cAMP, inhibition by muscarinic agents. AB - The K+ current induced by isoprenaline acting on beta-adrenergic receptors in Xenopus laevis has been studied in oocytes still surrounded by their follicular cells and inner ovarian epithelium. Forskolin, an adenylate cyclase activator, induced a similar K+ current and when used at subliminal concentration it potentiated the current induced by isoprenaline. Inhibition of phosphodiesterase by methylisobutylxanthine also enhanced the response to isoprenaline. 8-Br-cAMP, a permeant analogue of cAMP also produced a K+ current. Acetylcholine produced a long lasting inhibition of the isoprenaline current. This inhibition was not seen in the presence of atropine. It is concluded that the K+ current induced by the activation of beta-adrenergic receptors in the oocyte is mediated by an intracellular rise of cAMP. PMID- 2579402 TI - Thymic epithelial cells of severely undernourished mice: accumulation of cholesteryl esters and absence of cytoplasmic vacuoles. AB - The thymic epithelium was compared in weanling male and female CBA/J mice when fed ad libitum and when subjected to severe food intake restriction for 14 days. The restriction protocol elicited predominantly a metabolic response to caloric deficit rather than to protein deficiency. Electron microscopy revealed intracytoplasmic accumulations of large, circular, homogeneously electron-dense profiles (with no limiting membrane) in a high proportion of cortical and medullary epithelial cells of thymuses from restricted mice, but not from controls. The electron-dense material was not preserved in the absence of osmium. Thin-layer chromatography (TLC) indicated elevated levels of free and esterified cholesterol, particularly the latter, in whole thymus extracts of restricted mice. Measurements of total cholesterol levels in the thymic extracts were consistent with the results obtained by TLC. In addition, cryostat sections of thymuses from restricted mice, but not from controls, exhibited numerous stained foci throughout the cortex and medulla when treated with oil red O (a general neutral lipid stain) or by the Schultz procedure which is specific for cholesterol. Collectively the results suggest accumulations of cholesteryl esters, together with some free cholesterol, as non-membrane-bound droplets in the cytoplasm of thymic epithelial cells of undernourished mice. It is also of interest that the lipid-laden epithelial cells exhibited none of the cytoplasmic vacuoles observed in controls and believed to be important in thymic hormone secretion. This work provides the first direct evidence of thymus epithelial abnormalities in severe protein-energy malnutrition. PMID- 2579403 TI - Effects of sodium saccharin on the activity of trypsin, chymotrypsin, and amylase and upon bacteria in small intestinal contents of rats. AB - Rats fed a diet containing 2.5% sodium saccharin (NaSacc) displayed a rapid (24 36 hr) increase in tryptic and chymotryptic activity in the lower half of the small intestine and the cecum compared with control animals. Cecal pH of rats fed NaSacc was lower than controls. The effect of NaSacc on enzymatic activity of intestinal contents and on indigenous bacterial microflora was studied further in vitro. Intestinal contents incubated anaerobically with or without NaSacc revealed that the presence of NaSacc led to higher tryptic and chymotryptic activity and higher final pH. Changes in pH do not appear, however, to be important for the increased proteolytic activity induced by NaSacc since autodigestion of trypsin and chymotrypsin in filter-sterilized samples was only slightly affected by pH during in vitro incubation. Amylolytic activity, on the other hand, was stabilized by higher pH values. Saccharin stabilized chymotryptic and led to almost complete loss of amylolytic activity during incubation of filter-sterilized samples maintained at adjusted pH values. The amount of reducing sugars remaining in the NaSacc-containing contents from either cecum (in vivo) or from in vitro incubation of unsterilized small intestinal samples was greater than controls not containing NaSacc. The growth of six bacterial strains isolated from small intestinal contents and incubated in laboratory media was inhibited by NaSacc. Extracellular proteolytic activity from bacterial sources was undetectable after incubation of intestinal bacteria in laboratory media. The present results suggest that the effect of NaSacc upon digestive enzyme composition in the small intestine of rats is not mediated through a direct physiological effect of NaSacc on pancreatic exocrine secretion. It is hypothesized that an inhibition of enzymatic activity by NaSacc in the small intestine and the bacteriostatic effect of NaSacc on bacteria may be responsible for the increased proteolytic activity observed in vivo in the cecum following the feeding of a NaSacc-containing diet to rats. PMID- 2579404 TI - Segmental homology between T-cell receptors and immunoglobulin variable regions: evidence that antisera to synthetic JH1 peptide react with murine and human T cell products. AB - To determine precisely the nature of serological determinants shared between T cell surface molecules and immunoglobulin variable regions, the capacity of antisera directed against a synthetic peptide corresponding to the entire JH 1 region of classical immunoglobulin plus five residues of the D region were tested for their capacity to bind to T-cell membranes and isolated T-cell products. The anti-JH 1 antisera reacted with normal and monoclonal in vitro grown T-cell lines as judged by microhemagglutination and binding in enzyme-linked immunosorbent assays. Immunologically cross-reactive membrane components disclosed by immunoblot transfer analysis ("Western blots") consisted of major components in the molecular weight range 30-35,000 and minor components in the range 65-70,000. The major product of the human T-cell leukemia line MOLT-3 had an approximate mass of 34,000 Da, a value consistent with the predicted size of the molecule specified by the recently described putative T-cell receptor gene YT35. The 65 to 70,000-Da components are most probably tightly associated dimers of the 30 to 35,000-Da forms. It was possible to align the JH sequences of molecules reactive with the anti-JH 1 antisera and other characterized VH sequences of molecules known to be cross-reactive with T-cell products. This facilitated a comparison disclosing clear segmental homology between the protein sequence derived from the YT35 gene and immunoglobulin VH framework regions sharing approximately 50% of sequence identity. The identification of VH-related T-cell products (termed VT bearing molecules) with products of putative T-cell receptor genes gained further support by N-terminal sequence of the 68,000-Da product of the 70-N2 T-cell line which showed homology to the predicted N-terminal region of the YT35 product. These serological and protein chemical data, coupled with the comparison to gene sequence, show that T-cell components that bear serological determinants cross reactive with VH show segmental homology with products of putative T-cell receptor genes and immunoglobulin VH. PMID- 2579405 TI - Prostaglandins, alpha-adrenergic receptors and lipolysis in hamster fat cells. AB - In hamster fat cells, PGE2, PGI1 and clonidine (alpha 2-adrenoceptor agonist) were shown to inhibit markedly lipolysis stimulated by methylisobutylxanthine (MIX) (2 X 10(-4) M) and slightly that provoked by isoprenaline (5 X 10(-7) M). The similar inhibitory actions of the alpha 2-adrenoceptor agonist clonidine and PGE2 on lipolysis stimulated by MIX led us to examine possible reversal of the antilipolytic effect of PGE2 by yohimbine (alpha 2-adrenoceptor antagonist). However, the absence of an effect of yohimbine on PGE2, antilipolytic action indicated that the PGE2 receptor was different from the alpha 2-adrenoceptor of hamster fat cells. In these studies, PGE2 was shown to be a more potent antilipolytic agent that PGI2 (IC50 values 2 X 10(-9) and greater than 10(-4) M respectively). PMID- 2579407 TI - The 1984 Association Lecture of the Hospital Physicists' Association. Man and his environment. AB - Man has multiplied and become civilised by changing his environment to suit himself, especially by the development of agriculture. The near-elimination of infectious diseases among the young and middle-aged has increased the cancer death rates in Britain, which mainly affect the elderly, to 130 000 a year. A large proportion of cancers are initiated by environmental factors which should be discoverable and removable. Natural radon may be responsible for up to 400 cancer deaths annually and radiation from the nuclear industry for one or two more. An important number of cancers must be due to air pollution from the burning of coal and oil, which are also injuring the wildlife of the northern hemisphere and which, by increasing the concentration of carbon dioxide in the air, may be changing the climate of the whole planet. PMID- 2579406 TI - Determination of dopamine, norepinephrine, serotonin and their major metabolic products in rat brain by reverse-phase ion-pair high performance liquid chromatography with electrochemical detection. AB - A method is described for the separation and quantitation of catecholamines, serotonin, and their major metabolites with use of reverse-phase, ion-pair liquid chromatography with electrochemical detection. This method employs columns packed with a microparticulate C-18 resin, octyl sodium sulfate as the ion-pairing agent, and isocratic elution with a citrate-phosphate buffer containing methanol. Conditions are described for the separation of norepinephrine, normetanephrine, 3 methoxy-4-hydroxyphenylglycol, epinephrine, metanephrine, dopamine, 3,4 dihydroxyphenylacetic acid, homovanillic acid, serotonin, and 5-hydroxyindole-3 acetic acid and for their quantitation in extracts of rat brain tissue. PMID- 2579408 TI - Histologic assessment of nerve regeneration in the rat. AB - This study reports the degree of spontaneous regeneration that will occur in the sciatic nerve of a rat 5 months after complete resection of the nerve. In 30 animals, the sciatic nerve was excised. Histological assessment at 5 months revealed evidence of regeneration for a variable distance (mean 23.7 mm +/- 6.4 mm). Histological sections were studied at 1-cm intervals along the length of the nerve. Evidence of compartmentation with "minifascicle" formation was noted. The orientation of the nerve fibers was parallel to the long axis of the nerve. This study assessing spontaneous regeneration is meant to serve as a control for other studies evaluating the effect of factors that may influence nerve regeneration in the rat model. PMID- 2579409 TI - Ritual man: on the outside of Herbert's poetry. PMID- 2579410 TI - In search of the saddiq: visitational dreams among Moroccan Jews in Israel. AB - Folk veneration of saints (hagiolatry) plays a major role in the lives of many Moroccan Jews living in Israel and constitutes a basic ingredient of their distinctive ethnic identity. In this context, pilgrimages to the saint's tomb and visitational dreams, in which he appears in person or in some symbolic guise, are related phenomena through which the linkage to the saint is maintained and his blessing is granted to his adherents. This paper is concerned with visitational dreams collected among Moroccan Jews in a major pilgrimage center in northern Israel. An attempt is made to show how personal concerns of the dreamers are mediated through the culturally shared idiom of the saint. We discuss the basic structure of visitational dreams, the major life problems conveyed by them (drawing on illustrations from the dream collection), their therapeutic qualities and their significance in the framework of the pilgrimage to the saint's sanctuary. PMID- 2579411 TI - Psychiatric consultation with a noncooperative, depressed stroke patient. PMID- 2579412 TI - [Radiotherapy of pancreas cancer--literature review]. AB - Resection is the treatment of choice in organ-limited pancreatic cancer. In locally or regional, not completely resectable pancreatic cancer other therapeutic modalities are called upon: external beam radiotherapy results in relief of pain in 50% and average survival rate of about 10 months according to recent series in the literature. Loco-regional tumor control can be improved by intraoperative electrons or interstitial implantation of radioactive sources. - The combination of monochemotherapy (5-fluorouracil) and 40 Gy radiotherapy is well tolerated and tends to prolong survival also if given after curative resection. PMID- 2579413 TI - Basal cell carcinoma. A case history of a patient with a basal cell carcinoma. PMID- 2579414 TI - [Hepatic artery embolization as a palliative treatment for malignant hepatic tumors: presentation of our experience]. PMID- 2579416 TI - Plasma fibronectin in relation to surgical trauma. AB - Plasma concentrations of fibronectin, alpha 2-macroglobulin and orosomucoid were monitored immunochemically in 20 patients before, during and after surgery. At 2 h after the induction of anaesthesia fibronectin concentrations were lowered 31 +/- 6% (SEM) compared to values obtained 1-3 d preoperatively. However, the fibronectin concentration decreased 17 +/- 5% (SEM) compared to preoperative values at the beginning of surgery. Most of the decline was thus not caused by the operative trauma. The perioperative changes in fibronectin concentrations did not differ from those found in alpha 2-macroglobulin and, up to 2 h postoperatively, orosomucoid. PMID- 2579415 TI - Investigations into the association of retroviruses with ovine lymphoma. AB - To determine whether retroviruses are associated with sporadic ovine lymphoma, suspension cell cultures of four lymphomas and one control lymph node were labelled with tritiated uridine. Following differential and sucrose density gradient ultracentrifugation of their media a peak of radioactivity was found at a density of 1.15 to 1.18 g ml-1 in preparations from the cell cultures of two lymphomas and the normal lymph node. Sedimentation velocity centrifugation of the sodium dodecyl sulphate-treated radiolabelled material found an approximate sedimentation value of 7S. The assay for RNA directed DNA polymerase in ultracentrifuged pellets of media from cultures of 15 lymphomas and one control lymph node found activity in material from four lymphomas and the control node cultures. However, little variation in incorporation kinetics occurred with changes in assay conditions and activities were not associated with particles of density 1.15 g ml-1. It was concluded that the detected activities were not retroviral in origin. PMID- 2579417 TI - Two human IgM myeloma proteins with unusual specificities for streptococcal carbohydrate-associated epitopes. AB - Five hundred and fifty human sera from patients with IgM myeloma or Waldenstrom's macroglobulinaemia were screened by a solid-phase enzyme-linked immunoassay for binding to the carbohydrate of group A streptococci (A-CHO). Two of them (AC8 and AC179) contained immunoglobulin, which bound specifically to A-CHO even at serum dilutions of 1:10(7). Using synthetic oligosaccharides coupled to protein for inhibition studies, the fine specificities of AC8 and AC179 were determined. AC179 is directed to alpha-linked rhamnose oligosaccharides. AC8 appears to be specific for N-acetyl-D-glucosamine (GlcNAc) side chains beta(1----2)-linked to rhamnose, whereas GlcNAc side chains in A-CHO are reported to be beta(1----3) linked to the rhamnose backbone. Naturally occurring anti-A-CHO antibodies consist mainly of low-affinity antibodies to such beta(1----3)-linked GlcNAc. In contrast, both myeloma antibodies show more than 10 times higher relative affinities to A-CHO than antibodies prepared from normal human serum (anti-GlcNAc and anti-A-CHO, respectively) by selection for high affinity in the elution procedure. AC179 induced complement activation in the presence of A-CHO. PMID- 2579418 TI - In vivo isotype regulation of humoral responses to dextran B1355 in BALB/c mice. Double-class IgG3/IgM producers as a function of age. AB - This report shows that, in 8- to 10-month-old BALB/c mice immunized intraperitoneally with dextran B1355, approximately 75% of IgG3 anti-alpha (1--- 3) polyglucan (anti-dex) plaque-forming cells (PFC) detected in the spleen were identified as double-Ig class producers secreting simultaneously IgG3 and IgM antibodies with the same specificity for the dex epitope. Under the same conditions of immunization, however, IgA anti-dex PFC were mostly single-class secretors. IgA PFC developed in the spleen in highest numbers (equal to IgM), but in Peyer's patches IgA PFC were sevenfold more numerous than IgM. Furthermore, spleen IgG3 anti-dex PFC responses were low compared with spleen IgA and IgM anti dex PFC responses and appeared only late in ontogeny. The possibility is discussed whether a TH dependence of the IgA anti-dex response and a TH independent generation of the IgG3 response are responsible for the different pattern of isotype expression. PMID- 2579419 TI - Antigen-binding molecules of T cells: distinction from MHC-restricted molecules and segmental homology to immunoglobulin VH and T-cell receptor genes. PMID- 2579420 TI - [Late improvements in chronic schizophrenics]. AB - The author raises the issue of patients' late improvement with chronic schizophrenia. Five out of 289 reassessed chronic schizophrenics--1.7% of that population--have been found improved. Two cases are described in detail and finally some hypotheses are suggested in relation to the possible mechanisms underlying these rare courses of schizophrenia. PMID- 2579422 TI - [Psychopathology and genetics of schizophrenia]. AB - The history of psychopathology of schizophrenia from Kahlbaum to Kraepelin is reviewed: Bleulers concept of symptoms and his construct of primary disorder. Today symptomatology and syndrom - construction by modern techniques of evaluation are prominent aims of research. The ego-psychopathology is an example of a new empirical approach. The hereditary predisposition for the manifestation of schizophrenialike psychoses is empirically well founded. PMID- 2579421 TI - [Personal development in schizophrenia therapy]. AB - Gaetano Benedetti introduced the psychotherapy of schizophrenics in Burgholzli in the early fifties. In this paper he reviews the development of his work and appreciates the significance of Bleuler's concept of schizophrenia. He then traces an outline of his communicative psychopathology: Of primary importance for the psychotherapist is the awareness that there are also anti-psychotic intentions in the patient which are trying to be expressed through the psychotic figurations. The psychotherapist accepts the psychotic experiences of his patients in order to transform them through his identification with them, resulting in the positivization of psychopathology. It is, as if here, in this field of psychotherapeutic duality, that the otherwise lost dimension of humanity in psychosis can find expression. PMID- 2579424 TI - [Premorbid personality of schizophrenic patients]. AB - This review summarizes different studies on schizophrenics regarding their premorbid personality. Schizophrenics do not average other social classes (father's profession) than endogenous or reactive depressives do, nor do they differ from the general population in that respect. On the other hand, schizophrenics show an inferior schooling achievement, as compared to depressives, and partially for that reason belong to lower social classes prior to the onset of their illness. Detailed studies of the respective social network show that schizophrenics develop in a less emancipated manner than controls, that they stick more to their families of origin, and that they engage in fewer interpersonal relationships. The latter not only are quantitatively inferior to those of healthy people, but also in quality; their relationships are often distant and alienated. In a prospective epidemiological study, 28 schizophrenics were assessed with a multi-dimensional personality test, the FPI, on average 2 years prior to the onset of their illness. The selfrating results show that schizophrenics are introverted premorbidly, as compared to control groups; it is assumed that this personality trait will be understood as "schizoid" in non selfrating. Surprisingly, schizophrenics premorbidly have a normal neuroticism score, i.e. they are not more irritable, more aggressive, more depressive or emotionally unstable than controls. PMID- 2579423 TI - [EEG correlates of information processing in acute and remittent schizophrenic patients]. AB - Studies of the EEG correlates of information processing in normals indicate that different cognitive processing of information is correlated with different functional brain states. Studies in experimental psychology have demonstrated a communication and performance deficit in schizophrenics which indicates a deviation in one or more stages of information processing. Accordingly it can be hypothesized that the functional brain states as manifested in the EEG during information processing in schizophrenics are different from these states in normals or former schizophrenics. The paper tested this hypothesis in drug-free acute and former schizophrenics, neurotics and normals. The results indicate 1) that acute schizophrenics show a deviant electrical brain state during information processing; 2) former schizophrenics in a good clinical remission have electrical brain states during information processing which in some aspects are normalised, and in other aspects still differ from these states in normals and neurotics. The importance of these physiological findings for the assessment of the efficacy of the biological and psychological treatments in schizophrenia is discussed. PMID- 2579425 TI - [Bibliography of Manfred Bleuler 1928-1983]. PMID- 2579426 TI - [Difficulties in neuroleptic treatment of schizophrenic patients]. AB - During the treatment of schizophrenic patients with antipsychotic drugs the following difficulties must be considered: Lack of predictability of therapeutic outcome, extrapyramidal side effects, "pharmacogenic" depressions. The most important presupposition for a successful handling of these difficulties is an intensive psychopharmacological training of psychiatrists. PMID- 2579428 TI - [Psychiatric treatment of schizophrenic patients in the clinic]. AB - The development of individual psychotherapy, family therapy, and nursing activities during the last thirty years is pointed out. Clinical treatment will be dehumanized if hospital staff is reduced out of financial reasons. PMID- 2579427 TI - [The schizophrenic as ambulatory patient]. AB - The growing number of schizophrenics who are taken care of as out-patients has led to new questions: Which is the symptomatology and psychopathology, which are the life-styles and treatment needs of such patients? The specific vulnerability of schizophrenics and some basic rules of their extra-mural care are discussed. PMID- 2579429 TI - [Cerebral atrophy and dementia in Parkinson disease]. AB - The intellectual impairment appearing during the Parkinson's disease has been analysed and compared with the severity of the motor deficit respectively with the presence of the cerebral atrophy determined by computed tomography. The organic mental syndrome was more frequently observed in males and well correlated with the degree of cortical and subcortical atrophy. PMID- 2579430 TI - Neoplastic transformation of human epidermal keratinocytes by AD12-SV40 and Kirsten sarcoma viruses. AB - Recent investigations have begun to dissect the number and nature of genetic alterations associated with cancer cells. In the present study, primary human epidermal keratinocytes acquired indefinite life-span in culture but did not undergo malignant conversion in response to infection with a hybrid of adenovirus 12 and simian virus 40. Addition of Kirsten murine sarcoma virus, which contains a K-ras oncogene, to these cells induced morphological alterations associated with the acquisition of neoplastic properties. These findings demonstrate the malignant transformation of human primary epithelial cells in culture and support a multiple-step process for neoplastic conversion. PMID- 2579431 TI - Heterogeneity of 5S RNA in fungal ribosomes. AB - Neurospora crassa has at least seven types of 5S RNA genes (alpha, beta, gamma, epsilon, delta, zeta, and eta) with different coding regions. A high resolution gel electrophoresis system was developed to separate minor 5S RNA's from the major 5S RNA (alpha). A study of several Neurospora crassa strains, four other species in the genus Neurospora, members of two closely related genera, and three distantly related genera demonstrated that 5S RNA heterogeneity is common among fungi. In addition, different 5S RNA's are present in Neurospora ribosomes. The finding that fungal ribosomes are structurally heterogeneous suggests that ribosomes may be functionally heterogeneous as well. PMID- 2579432 TI - Expression of myelin-associated glycoprotein by small neurons of the dorsal root ganglion in chickens. AB - Biochemical and immunocytochemical investigations have shown that myelin associated glycoprotein (MAG) is exclusively related to myelin and myelin-forming cells in mammals. In the present study it was found that dorsal root ganglia in young chickens display MAG-immunoreactive material in most small sensory neurons. The presence of MAG at the surface of small sensory neurons raises the question of whether this glycoprotein acts as a cell adhesion molecule in lower vertebrates. PMID- 2579433 TI - Bovine leukemia virus-related antigens in lymphocyte cultures infected with AIDS associated viruses. AB - An earlier finding that lymphocytes from African patients with the acquired immune deficiency syndrome (AIDS) react with rabbit antiserum to purified antigens of bovine leukemia virus (BLV) prompted a study of the possible cross reactions between a BLV-infected ovine cell line and human lymphocytes inoculated with a strain of lymphadenopathy syndrome-associated virus (LAV). A solid-phase radioimmunoassay was used to detect antigenic markers of the retroviruses. Crude extracts from short-term cultures of lymphocytes infected with LAV bound rabbit antisera to the LAV glycoprotein gp13 (molecular weight 13,000) and the BLV proteins p24 and gp51, but did not bind antibodies to the p24 of human T-cell leukemia virus type I (HTLV-I). Antiserum to LAV gp13 reacted with an ovine cell line producing BLV but also weakly with virus-free ovine cells. Lymphocyte cultures from four African patients with AIDS expressed BLV-related antigens within 6 to 10 days of culture, at the moment when particle-bound reverse transcriptase was produced. BLV-related antigens were induced in lymphocyte cultures from healthy individuals by addition of filtered supernatant or irradiated cells of the original culture. The antisera to BLV used in this study may prove useful for the detection of AIDS-associated viruses in short-term cultures of lymphocytes from AIDS patients or their contacts. PMID- 2579434 TI - A new approach to cystic fibrosis. PMID- 2579435 TI - Hypomethylation of DNA from benign and malignant human colon neoplasms. AB - The methylation state of DNA from human colon tissue displaying neoplastic growth was determined by means of restriction endonuclease analysis. When compared to DNA from adjacent normal tissue, DNA from both benign colon polyps and malignant carcinomas was substantially hypomethylated. With the use of probes for growth hormone, gamma-globin, alpha-chorionic gonadotropin, and gamma-crystallin, methylation changes were detected in all 23 neoplastic growths examined. Benign polyps were hypomethylated to a degree similar to that in malignant tissue. These results indicate that hypomethylation is a consistent biochemical characteristic of human colonic tumors and is an alteration in the DNA that precedes malignancy. PMID- 2579436 TI - Rationale behind the development of low molecular weight heparin derivatives. AB - There is now considerable evidence that the antithrombotic and the hemorrhagic effects of heparin can be dissociated by using low molecular weight heparins and by using heparin with low affinity to AT III. The findings with low-affinity heparin suggest that hemorrhage is contributed to by heparin properties that are independent of AT III binding and thus of their major anticoagulant effect. The current evidence supports the suggestion that the hemorrhagic effect of heparin is contributed to by a reversible platelet functional defect that is relatively less important than its AT III dependent anticoagulant effect for preventing experimental venous thrombosis. Whether these promising results in animals also apply to human thromboembolism disease will require careful evaluation by suitably designed clinical trials. PMID- 2579437 TI - Molecular weight of heparin versus biologic activity. Some additional considerations. PMID- 2579438 TI - Gastric adenocarcinoma--management of the primary disease. AB - While it will be another decade before the results are apparent, the past decade has sown the seeds of new generation of concepts regarding the initial management of gastric adenocarcinoma. Those seeds will come to flower when we fully utilize the management tools that have been developed. Endoscopy provides the opportunity for earlier diagnosis of gastric cancer. More liberal use of gastroscopy and cytology when x-rays are not completely diagnostic should identify the still surgically curable tumor. An improved understanding of the routes of tumor spread -by invasion and metastases--have identified a number of practical alterations to the surgical procedures for the removal of gastric adenocarcinoma arising from various sites in the stomach. Suggestions for effective adjuvant therapies, based on the realization that most gastric cancer has become a systemic disease by the time of diagnosis, are apparent from the clinical trials to date: Local control of microscopic disease with radiotherapy and treatment of transperitoneal tumor spread by the intraperitoneal route are logical additions to systemic therapy. More careful and thorough pathologic examination of resected tissues, with adjuvant treatment planning based on the results of that examination, should alter what has in the past been the grim prognosis of this disease. Careful follow-up evaluation and attention to nutrition can improve the quality of the patient's life, just as carefully planned antineoplastic therapy can improve its duration. PMID- 2579439 TI - Diagnosis and treatment of malignant pleural effusion. PMID- 2579440 TI - Third-line salvage chemotherapy in Hodgkin's disease. AB - CEP (CCNU, etoposide, and prednimustine) was tested as third-line chemotherapy in 40 patients resistant to both MOPP and ABVD. The observed response rate (complete remission, 35%, and partial remission, 25%) is encouraging. Treatment was generally well tolerated and all acute side effects were reversible. PMID- 2579441 TI - ProMACE-MOPP combination chemotherapy for diffuse lymphomas. AB - Until the mid 1960s the advanced stage, high grade non-Hodgkin's lymphomas were rapidly progressive, fatal diseases with few patients remaining alive at 5 years. Studies conducted at the NCI demonstrated that 47% of all patients with advanced stages of diffuse mixed, large cell, and undifferentiated non-Burkitt's lymphoma could achieve a complete remission documented by reevaluation of all initially involved sites following treatment with either the C-MOPP or BACOP combination chemotherapy regimens. Furthermore, 70% to 80% of these complete responders had long-term disease-free survival tan-tamount to cure. The third generation of NCI studies, termed the ProMACE-MOPP flexible induction program, significantly improved these results. Complete remissions were achieved in 74% of all patients and 73% of these remain disease free in excess of 3 years. Myelosuppression was dose limiting with a 10% septic death rate. Studies are currently underway in an attempt to minimize the toxicity of the new regimen, while preserving the increased complete response rates and long-term survival. PMID- 2579442 TI - VP-16 in combinations for first-line treatment of malignant germ-cell tumors and gestational choriocarcinoma. AB - VP-16 (VePesid) was incorporated into combinations for first-line treatment of patients with malignant germ-cell tumors or gestational choriocarcinoma. The basic combination consists of POMB (vincristine, methotrexate, bleomycin, and high-dose cis-platinum) and ACE (VP-16, actinomycin D, and cyclophosphamide). Patients receive two courses of POMB, then ACE, then POMB again. Patients with larger volume disease continue with POMB and ACE until biochemical remission is achieved, as indicated by tumor marker levels. Of 112 male patients with malignant germ-cell tumors, some of whom had previous radiotherapy or chemotherapy, and more than 50% of whom had advanced disease, the current survival rate is 87%. The survival rate is 77% for the worst-prognosis patient group. Patients with brain metastases from germ-cell tumors have not required surgery or radiotherapy to achieve a durable complete remission. Among patients who have multiple resistance to drugs such as vinblastine, bleomycin, and cis platinum, 50% have achieved remission when treated with the EP/OMB schedule (VP 16 and cis-platinum alternated with vincristine, methotrexate, and bleomycin) repeated at short intervals. In 76 drug-resistant patients with gestational choriocarcinoma (medium risk), VP-16 was given intravenously (IV) 100 mg/m2/d for five days as initial therapy, with methotrexate given 11 to 13 days later. Overall response rate including partial response and improvement is 78%. In high risk gestational choriocarcinoma patients, a weekly schedule of chemotherapy, alternating EMA (VP-16, methotrexate, actinomycin D, and folinic acid) with CO (vincristine and cyclophosphamide), has resulted in an overall survival of 84%; survival in patients who received previous chemotherapy is 73%; and survival in those who did not receive previous chemotherapy, 93%. Mucosal toxicity has not been a major problem. It is recommended that in patients with germ-cell tumors and in medium- and high-risk gestational choriocarcinoma patients, VP-16 be used in initial therapy and not be retained for relapse therapy only. PMID- 2579443 TI - Use of radiographic projections of knee. AB - A study to determine the routine radiography practice for the investigation of acute trauma cases and those with suspected arthritis of the knee was carried out by questionnaires sent to radiologists in 41 countries. The role of radiology in the investigation of chondromalacia patellae was also ascertained. Some of the reasons for the diversities of practice are discussed. The necessity for further views of the knee to supplement the two standard projections was assessed for various diagnostic entities. It became clear that if occult fractures were not to be missed, patients with knee effusions following acute trauma required additional views if a lesion was not shown by the anteroposterior (AP) and lateral views. In contrast, two views of the knee sufficed for examination of most entities affecting the knee. PMID- 2579444 TI - Pleuropulmonary Whipple's disease. AB - Patients with Whipple's disease usually have gastrointestinal complaints. A broad array of extraintestinal symptoms may precede gastrointestinal complaints by years. In the patient described herein, five years of polyserositis evolved into a nearly fatal illness. Electron microscopy of an intra-abdominal lymph node biopsy led to diagnosis and successful therapy. PMID- 2579445 TI - Klebsiella oxytoca endocarditis after transurethral resection of the prostate gland. AB - Klebsiella oxytoca endocarditis developed in an 87-year-old man after transurethral resection of the prostate gland. He was treated for K oxytoca urinary tract infection and septicemia seven weeks before admission. Fever and bacteremia persisted for ten days during therapy for endocarditis. He was treated with a combination of cefazolin and tobramycin for six weeks. Despite peak serum bactericidal titers of only 1:4, the patient recovered completely and was apparently healthy at followup two years later. PMID- 2579446 TI - Chinese hamster cells deficient in ornithine decarboxylase activity: reversion by gene amplification and by azacytidine treatment. AB - A group of Chinese hamster ovary (CHO) cell mutants deficient in ornithine decarboxylase (ODC) activity are described and compared to the prototype mutant reported previously (21). Although all mutants belong to the same complementation group, they can be divided into two classes: those with some residual enzyme activity and those with no activity. All mutants are putrescine auxotrophs, but they differ in their ability to utilize the enzyme's substrate, ornithine, a property which correlates with the amount of residual enzyme activity. The mutants also differ in their frequency of reversion to prototrophy. The leaky mutants revert at a high rate by overproducing a partially defective enzyme by a gene amplification mechanism similar to that leading to the ornithine analog resistant mutants which have elevated enzyme levels. Spontaneous reversion in the null mutants is rare. However, one null mutant, which was induced with ethyl methane sulfonate and which makes ODC mRNA but no active enzyme, is nevertheless revertible with 5-azacytidine. We conclude that CHO cells are at least diploid at the ODC locus, but that only one allele is active. Further studies suggest the possibility that ethyl methane sulfonate is not just a classical mutagen but may also induce gene inactivations that are revertible by 5-azacytidine. PMID- 2579447 TI - [Local anesthesia for tooth extraction. 1. Pharmacology of local anesthetics]. PMID- 2579448 TI - The palliation of esophageal cancer. PMID- 2579449 TI - Treatment of proximal biliary tract carcinoma: an overview of techniques and results. AB - Proximal biliary tract cancer carries a dismal prognosis. Few patients have a curative option. However, worthwhile palliation can be achieved in many patients by relieving obstructive jaundice. An overview is presented to place in perspective the treatment methods described and the results obtained. PMID- 2579451 TI - Plasma beta-thromboglobulin is correlated with platelet adhesiveness to bovine endothelium in patients with diabetes mellitus. AB - We measured simultaneous plasma beta-thromboglobulin (BTG) and adhesion of 51Cr labelled, washed platelets to confluent, bovine aortic endothelial monolayers in 50 insulin-dependent diabetic patients and 30 normal subjects (respective mean ages (+/- SD) = 45.1 +/- 16.4 and 45.8 +/- 17.2 years). Compared to normal subjects without arteriosclerotic complications, diabetic patients had higher plasma BTG (34.8 +/- 1.8 (SEM) vs. 21.3 +/- 1.8 ng/ml) and platelet adhesiveness to endothelium (PAE) (3240 +/- 170 vs. 2430 +/- 120 X 10(3) platelets per well) (p less than 0.0002, respectively). Results in diabetic patients did not correlate with plasma glucose, hemoglobin AIa-c, known duration of disease, or sex; plasma BTG correlated with age (r = +0.36), and PAE correlated with plasma creatinine (r = +0.39). Those with clinically evident vascular disease, who were also older (47.8 +/- 2.6 (SEM) vs. 37.3 +/- 4.5 years, p less than 0.05), showed trends to higher plasma BTG (36.7 +/- 2.2 (SEM) vs. 28.8 +/- 3.4 ng/ml, p = 0.06) and PAE (3400 +/- 200 vs. 2800 +/- 280 X 10(3) platelets per well, p = 0.09). A strong correlation was found between plasma BTG and PAE in diabetic patients (r = +0.62, p less than 0.0001) either with or without vascular disease, which remained strong after statistical correction (partial Pearson correlation) for age and plasma creatinine, but not in normal subjects (r = +0.08, p greater than 0.1). These studies demonstrate that platelets in some diabetic patients are excessively adhesive to vascular endothelium, and that plasma BTG and platelet adhesiveness are intercorrelated. PMID- 2579450 TI - Comparison of tumour markers in malignant mesothelioma and pulmonary adenocarcinoma. AB - Immunohistological methods were used to investigate the presence of carcinoembryonic antigen, beta 1 pregnancy specific glycoprotein, beta subunit of human chorionic gonadotrophin, human placental lactogen, calcitonin, and keratin in formalin fixed tissue from 29 malignant mesotheliomas and 27 pulmonary adenocarcinomas. Malignant mesotheliomas were negative for tumour markers except for the beta subunit of human chorionic gonadotrophin and keratin, one and 13 cases respectively being positive for these. Pulmonary adenocarcinomas, however, were frequently positive for tumour markers--namely, carcinoembryonic antigen, beta 1 pregnancy specific glycoprotein, beta subunit of human chorionic gonadotrophin, human placental lactogen, calcitonin, and keratin. The presence of carcinoembryonic antigen and beta 1 pregnancy specific glycoprotein within an intrathoracic tumour is strong evidence against its being of mesothelial origin. PMID- 2579453 TI - [Care of patients with terminal cancer]. PMID- 2579452 TI - Comparison between the effect of pentosan polysulphate heparin and antithrombin III injections in antithrombin III deficient patients. AB - Pentosan polysulphate is an heparin analogue which acts via an antithrombin III (AT III) independent pathway. We compared the effect of this drug to that of heparin and AT III infusions in AT III deficient patients. Four patients with AT III congenital deficiency received on three different occasions: (i) an infusion of human AT III concentrate (20 U/kg or 40 U/kg), (ii) an intramuscular injection of pentosan polysulphate (2 mg/kg), (iii) a subcutaneous calcium heparin injection (100 U/kg). AT III infusion inhibits the excessive thrombin generation (46% of inhibition) observed in the plasma of AT III deficient patients during at least 12 hours, but does not modify the factor Xa formation. On the contrary, pentosan polysulphate has a marked effect on both thrombin (62% of inhibition) and factor Xa generation (57% of inhibition) still present 8 hours after injection. Heparin injection has the same effect, more prolonged, as pentosan polysulphate on thrombin generation but is not so effective on impairing factor Xa generation (27% of inhibition). The marked effect of pentosan polysulphate on thrombin and factor Xa generation in these patients is due to its AT III independent mechanism of action. PMID- 2579455 TI - Tracheal resection--state of the art. AB - Sleeve resection of the trachea and reconstruction by end-to-end anastomosis is seen as the method of choice in the treatment of short and long stenoses of the trachea following long-term artificial respiration and tumors. The experience with tracheal resection in 73 patients operated upon at 2 different thoracic units is analyzed. Postintubation was the main indication for operation in 63% of the patient population. The 30-day postoperative mortality rate was 8% with a total mortality of 19%. A satisfactory functional result was attained in 73% of the patients operated upon including those with malignant tumors. Restenoses occurred in 6 of the 73 patients who underwent surgery. Different approaches to tracheal resection were chosen in the 2 clinics and the possibility of mobilizing the larynx was used in a different way. A preference for resorbable material was noted regardless of the operative technique and has prevented restenosis. The diagnostic procedures considered mandatory, the indications for surgery and the various operative techniques are discussed. PMID- 2579454 TI - Study of the risk factors related to early mortality following combined mitral valve replacement and coronary artery bypass grafting. AB - Combined mitral valve replacement (MVR) and coronary artery bypass graft (CABG) operation was performed in 62 consecutive patients at the Wessex Cardiothoracic Centre, Southampton, from 1972 to 1983. There were 43 men and 19 women. The mean age was 61 years. Ten patients were in New York Heart Association (NYHA) functional class II, 34 in class III and 18 were in functional class IV. Mitral regurgitation was predominant in 50 patients and mitral stenosis in 12. Emergency operations were performed in 9 patients and elective operations in 53. There were 5 operative deaths (8.06%), 2 in patients having elective operations (2/53 = 3.7%) and 3 in those having emergency operations (3/9 = 33.3%). Significant factors related to early death were NYHA functional class, timing of surgery, etiology and type of valve lesion, increased pulmonary vascular resistance and low cardiac index. PMID- 2579456 TI - Open mitral commissurotomy. A new plea for an old operation. AB - From April 1974 through December 1982, 673 patients underwent surgery for isolated mitral valvular disease. Valve replacement was mandatory in 507 patients; of these, 255 received low-profile mechanical (mainly Bjork-Shiley) prostheses and 252 bioprostheses. In 166 patients the mitral valve was amenable to reconstructive repair. This analysis is concerned exclusively with a subset of 127 patients, in whom open mitral commissurotomy was carried out (104 females and 23 males with a mean age at the time of operation of 45.5 years). There were 2 postoperative deaths, both due to intractable arrhythmias: one on the 4th postoperative day and one 6 years after surgery, giving a cardiac-related mortality of 1.5%. Thromboembolic complications were observed in 5 patients, none of whom developed permanent neurological deficits. There were 2 non-cardiac related deaths: one of cancer and one of viral pneumonia. Mitral valve replacement was subsequently required in 2 patients at 2 and 7 years, respectively, after commissurotomy. Surgical intervention is pending for 2 further patients who appear likely to require valve replacement. Based on actuarial curves, the analysis of these results shows that, provided valvular morphology is suitable, open mitral commissurotomy is superior to valve replacement with respect to mortality rate and long-term survival. PMID- 2579457 TI - Aortic root enlargement with glycerol-preserved homologous dura mater patch during aortic valve replacement. AB - Aortic root enlargement with a patch is sometimes indicated either to prevent aortic homograft valve distortion during implantation or to facilitate easy, tension-free closure of the aortotomy. Patches made of prosthetic material have been widely used for this purpose. The use of autogenous pericardium has recently been reported. Although dura mater has been shown to have great strength, low antigenicity, athrombogenicity, easy availability in large sizes and rapid bonding to most tissues, its use for patch enlargement of the aortic root has not been previously documented. From 1979 to 1983, 38 patients had dura mater aortic root gussets placed during aortic valve replacement at the Southampton General Hospital. In all cases, the patches were placed to facilitate aortic closure, or to prevent homograft valve distortion by enlarging the non-coronary sinus. Aortic homografts were implanted in 11 patients, Carpentier Edwards' Xenograft valves in 16, Bjork-Shiley valves in 8 and Wessex Xenografts in 3 patients. All the patients survived and in a mean follow-up of 30 +/- 12.8 months (range 3 to 48 months) there has been no clinical evidence of patch failure due to leakage, rupture or aneurysm formation. These results suggest that glycerol-preserved dura mater is a satisfactory patch material for aortic root enlargement during aortic valve replacement. PMID- 2579459 TI - Aorto-coronary bypass surgery in 62 patients with severe left ventricular dysfunction--a follow-up study. AB - Long-term follow-up of 62 consecutive patients with severe left ventricular dysfunction (ejection fraction = less than 0.30) and disabling angina pectoris following aorto-coronary bypass surgery was investigated. Prior to surgery all patients had angina pectoris and a history of remote myocardial infarction, 35% were in congestive heart failure (CHF). Significant stenoses in 3 major coronary vessels were present in 51 patients (82%). An average of 3.5 grafts per patient were employed. Operative mortality (30 days) rate was 4.8% (3 patients) and 13 patients died during the following period. The average follow-up was 37 months (range: 6 to 116 months). At follow-up, the 5-year survival probability for these patients was 70% (SD = 9%). Thirty-one patients (67%) of the 46 survivors had complete relief of angina, but signs of CHF were still evident in 17 patients (36%). Compared to patients with ejection fractions above 0.30% (surgical mortality 1.4% and 5-year survival rate 94% (SD = 3%] the outcome of coronary artery bypass grafting in patients with poor left ventricular function showed a significantly higher surgical mortality (P = 0.03) and impaired long-term survival (P = 0.02). However, aorto-coronary bypass grafting can be performed in patients with severe left ventricular dysfunction with reasonable relief of angina and with an acceptable surgical mortality. PMID- 2579458 TI - Direct myocardial revascularization without cardiopulmonary bypass. AB - The authors present their experience with 160 patients who underwent coronary artery saphenous vein bypass revascularization without cardiopulmonary bypass. The distal sutures were performed with interruption of the coronary flow without any devices for perfusion of the coronary artery: the proximal sutures were made with tangential clamping of the aorta. Vessels most frequently revascularized were the anterior descending and the distal right coronary artery. Out of 597 patients who underwent bypass surgery in this period, this technique could be employed in 160 cases (26.8%). Hospital mortality was 3.1% (5/160) and perioperative myocardial infarction as determined by daily EKGs and CKMB occurred in 4 patients (2.5%). Control hemodynamic studies were performed in 41 of the 160 patients (25.6%) with a patency rate of 83.9% in the 62 grafts restudied. We conclude that direct myocardial revascularization can be performed safely without major difficulties and with efficient anastomoses. The main advantages of the technique are that it does not require the use of extracorporeal circulation and, consequently, the use of any blood, as well as its low cost due to shorter hospitalization periods. PMID- 2579460 TI - Subaortic stenosis--improved surgical approach. AB - In most cases of subaortic stenosis there is associated hypertrophic muscular stenosis. Classical surgical treatment by transaortic ventriculomyotomy can be assessed by bidigital septal examination through a complementary pulmonary arteriotomy as reported in this paper. Preoperative and postoperative trans stenotic subaortic pressure gradients were measured in 5 patients with a mean decrease of about 85 mmHg. Bidigital assessment of the residual septal thickness is likely to improve the results of transaortic ventriculomyotomy. PMID- 2579461 TI - Pseudocoarctation of the aortic arch associated with bicuspid aortic valve lesion: is it a surgical entity? AB - Three patients with bicuspid aortic valve lesion associated with pseudocoarctation of the aortic arch are presented. At operation, 2 had a bicuspid calcified stenotic aortic valve, and one a bicuspid non-calcified incompetent aortic valve. All required replacement of the diseased aortic valve. The pseudocoarctation was not corrected because it caused no hemodynamic abnormality. PMID- 2579462 TI - A comparative study of median sternotomy and standard thoracotomy wound skin closure methods. AB - Complications from skin closure after median sternotomy or standard thoracotomy incision, although uncommon, may be the source of undesireable morbidity and even death. A prospective randomized study of 3 different methods of wound skin closure has been carried out in 205 patients undergoing cardiothoracic surgery. These methods were: 1. continuous nylon vertical mattress suture; 2. continuous subcuticular absorbable (Dexon) suture; 3. adhesive sutureless skin closure (Op Site). All wounds were examined by independent observers at 5, 10 and 45 days after operation, and the findings were graded from 0 to 4. At 5 days, assessments were made of inflammation, edema, discharge and infection. At 10 days, attention was paid to the state of wound healing, and at 45 days to the final cosmetic appearance. The use of continuous subcuticular Dexon suture resulted in less discharge than Op-site (p less than 0.001) and less swelling or redness than nylon (p less than 0.001). Assessment of the final cosmetic appearance of the wound 6 weeks following surgery showed subcuticular Dexon to be superior to either nylon (p less than 0.01) or Op-site (p less than 0.01). PMID- 2579463 TI - Early surgical intervention in non-specific pleural empyema. AB - During a 4-year period, 18 patients were treated for non-specific pleural empyema. Nine patients were treated by closed intercostal drainage and 9 by early decortication. The length of time from initial treatment until complete resolution of the empyema and healing of the wound was compared between the groups and highly favored early surgery. We conclude that if an empyema does not show signs of regression after one week of drainage, surgical intervention is indicated. PMID- 2579464 TI - Tandem coarctation of the thoracic aorta with hypoplasia of the abdominal aorta. AB - After resection of the coarctation in a 3-year-old child with end-to-end anastomosis, a second membrane was found 1.5 cm lower. After a successful reoperation with an aortoplasty using Gore-Tex weak femoral pulses persisted. At catheterization, an area of irregular narrowing of the abdominal aorta just distal to the superior mesenteric artery was found with hypoplasia of the iliac and femoral arteries. In addition, this child had a two-sided cheilo-gnatho palatoschisis, vesicoureteral reflux and absence of gall bladder and hepato duodenal ligament. It is worthwhile considering that a second or third aortic abnormality can be hidden by a coarctation of the aorta. PMID- 2579465 TI - Rupture of a thoracic aortic aneurysm after prosthetic bypass from the ascending aorta to the descending aorta in a case of congenital aortic arch hypoplasia. AB - An unusual case of a successfully operated ruptured thoracic aneurysm of the aorta with bleeding into the atelectatic pulmonary left lower lobe and acute occlusion of the prosthesis in a 28-year-old woman is reported. The underlying disease was congenital aortic arch hypoplasia still present following implantation of a prosthetic bypass from the ascending aorta to the descending aorta performed in 1963. PMID- 2579466 TI - Internal mammary artery as a palliative systemic-pulmonary shunt in order to develop diminutive pulmonary arteries. AB - Diminutive pulmonary arteries remain a problem in the surgery of congenital heart disease. This is the second report of a case in which the internal mammary artery was successfully used to enlarge small pulmonary arteries by 50% within 9 months accompanied by improvement of the symptomatic state in a patient with pulmonary atresia and diminutive left pulmonary arteries. PMID- 2579468 TI - Anastomotic pseudoaneurysm after aorto-coronary bypass grafting. AB - A patient with a pseudoaneurysm at the site of the distal anastomosis of a saphenous vein coronary bypass graft is described. The aneurysm was resected. To our knowledge this is the first report of this complication after coronary bypass surgery. PMID- 2579467 TI - The surgical management of all the mechanical complications of myocardial infarction in the same patient. AB - A 48-year-old man sustained an inferior myocardial infarction resulting in a left ventricular aneurysm, ventricular septal defect and mitral regurgitation. Aneurysmectomy, closure of the ventricular septal defect, mitral valve replacement and coronary artery bypass were successfully performed. PMID- 2579469 TI - Left atrial ball thrombus. AB - The existence of a freely-floating thrombus in the left auricle is a rare finding in mitral pathology. Diagnosis by two-dimensional echocardiography has been described by various authors (1, 2, 3). In our case echocardiographic diagnosis of auricular thrombus was not possible at the beginning, given the bad ultrasonic window. Only when the thrombus floated freely in the left auricle it was detected in the region of the mitral valve, in spite of the bad ultrasound window. PMID- 2579471 TI - A modified needle holder for mitral valve surgery. AB - Maneuvers to improve access during difficult mitral valve surgery such as excessive traction on the mitral annulus, retraction and inversion are attended with increased risk of serious complications. A needle holder has been designed to facilitate the placement of sutures during mitral valve or other intracardiac procedures where access is difficult. PMID- 2579470 TI - Prevention of prosthetic disc immobilization by prolapsed sutures. AB - Disc immobilization by prolapsed sutures is a rare but potential risk after prosthetic heart valve replacement. We present here a simple technical modification used during prosthetic valve insertion, which can prevent the occurrence of such a complication. PMID- 2579472 TI - Late results of the surgical treatment for aortic dissections. AB - The results of 32 patients who had undergone surgery for aortic dissections were analyzed. Twenty-six patients were examined in hospital during the follow-up study while one patient refused the examination and 5 others had succumbed. The average follow-up was 42.6 months. Late functional status was generally good. Resuspension of the aortic annulus for incompetent aortic valves in type I and II dissections resulted in grave aortic regurgitation and death in one case, and in mild valvular incompetence in another case, while 5 patients had competent valves after resuspension. Computed tomography (CT) and angiographic studies frequently revealed residual changes such as double lumen of the aorta. Five subsequent aortic aneurysms were discovered, 4 of them having been reoperated after the study was completed. Periodical follow-up and screening of the aorta of operative survivors is recommended. PMID- 2579473 TI - 14th annual meeting of the German Society for Thoracic and Cardiovascular Surgery. February 14th, 1985 to February 16th, 1985, Bad Nauheim. Abstracts. PMID- 2579474 TI - Regulation of epidermal growth factor binding in a human keratinocyte cell line by 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) decreased the binding of epidermal growth factor (EGF) by the human keratinocyte cell line SCC-12F. This response was concentration dependent (half-maximal effective concentration, EC50 = 1.8 nM) and stereospecific. Scatchard analysis of EGF binding indicated that treatment with TCDD resulted in a loss of high-affinity (Kd = 0.28 nM) binding sites. This loss was accompanied by a concomitant inhibition of EGF-stimulated DNA synthesis. The kinetics for the decrease of EGF binding by TCDD and benzo[a]pyrene (BP) were compared. Inhibition of EGF binding by BP was maximal by 24 hr, with 90% recovery of EGF binding apparent by 48 hr. In contrast, TCDD treatment for 72 hr was required to produce maximal inhibition, and no recovery was evident up to 10 day after removal of TCDD from the growth medium. The data indicate that modulation of EGF binding by TCDD was mediated by the Ah receptor. Subsequent cellular responses, for example, inhibition of EGF-stimulated DNA synthesis, may be important in the expression of altered differentiation patterns observed in human epidermal keratinocytes exposed to TCDD. PMID- 2579475 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) enhances terminal differentiation of cultured human epidermal cells. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and isosteric halogenated analogs produce a spectrum of pathologic changes in the epidermis of humans. In this study, the actions of TCDD on cultured human epidermal cells were characterized to determine whether these cells are an appropriate in vitro model to examine the mechanisms of TCDD toxicity to human skin. The differential staining properties of TCDD-treated cultures indicated that TCDD decreased basal cell numbers and increased the degree of keratinization. Histologic examination of cross-sections of the cultures confirmed a loss of small nucleated cells and increased cell layering in response to TCDD. TCDD produced no change in total cell number or cell protein, but decreased the number of small (basal) cells and DNA synthesis. TCDD increased the number of cells containing spontaneous envelopes, as well as the number of envelope-competent cells. The quantitative changes observed in these parameters were consistent with a TCDD-induced commitment of proliferating cells to terminal differentiation. TCDD also decreased epidermal growth factor (EGF) specific binding. Maximal changes in EGF binding occurred after 4 days, and in small cell number after 5 days. The decreases in EGF binding and small cell number were stereospecific and concentration dependent (EC50, 1 to 2 nM), implicating the human Ah receptor in mediating these responses to TCDD. These data indicate that TCDD treatment produces hyperkeratinization in cultured human epidermal cells. It is proposed that TCDD acts on epidermal basal cells to enhance terminal differentiation through mechanisms regulated at least in part by the Ah receptor. PMID- 2579477 TI - A widely applicable analytical system for biological stains: reverse-phase thin layer chromatography. AB - The suitability of reverse-phase thin layer chromatography using a commercial adsorbant and aqueous methanol as an analytical tool for biological stains was investigated. The wide range of applicability of this technique is shown by the fact that of 120 dyes used as biological stains, 84 of diverse chemical character were successfully chromatographed by varying only the water content of the eluent. Unsuccessful chromatography was due either to immobility or streaking. Dyes exhibiting this behavior can be identified prior to chromatography by inspection of their structural formulae. Rf values were found to be significantly correlated with the calculated partition coefficients. This relationship provides information for the identification of dye components revealed by chromatography and a discussion of its use in the chemical characterization of various dyestuffs is presented. PMID- 2579476 TI - Lack of covalent binding of peroxisome proliferators nafenopin and Wy-14 643 to DNA in vivo and in vitro. AB - [3H][2-methyl-2-p-(1,2,3,4-tetrahydro-naphthyl)phenoxy] propionic acid (nafenopin), a hepatocarcinogenic peroxisome proliferator, when administered p.o. to normal intact and partially hepatectomized male F344 rats did not show any significant binding to DNA and RNA, but bound to proteins. The in vitro incubation of [3H]nafenopin and [3H]4-chloro-[6-(2,3 xylidino)pyrimidinylthio]acetic acid (Wy-14643), another peroxisome proliferator, with hepatic microsomes and calf thymus DNA also showed no significant binding of these chemicals to DNA. PMID- 2579478 TI - En bloc staining of articular cartilage and bone. AB - Blocks of canine and porcine articular cartilage were stained en bloc with Weigert's iron hematoxylin or Harris' hematoxylin with or without eosin Y counterstaining and cleared in methyl salicylate. The morphology and three dimensional relationships of chondrocytes were best demonstrated with Weigert's iron hematoxylin. The morphology of the cartilage and chondrocytes was superior to that in sections of routine hematoxylin and eosin stained, paraffin processed samples. The three-dimensional localization of intracellular lipids in individual and clones of chondrocytes was observed when cartilage samples were stained with oil red O and mounted directly in a water-based medium. Blocks of decalcified bone were stained en bloc with Weigert's iron hematoxylin and cleared with methyl salicylate. The three-dimensional orientation of osteocytes around osteonal canals, in circumferential lamellae, and in interstitial lamellae was demonstrated. The morphology of "cutting cones" in cortical bone also was observed. PMID- 2579479 TI - An improved technique for dissociating hepatocytes from fixed mouse liver for cytochemistry. AB - A refined version of a method described previously for dissociating hepatocytes from fixed liver is described. The objective was to develop a procedure that would dispense with the postosmication of previously fixed tissue. In the new procedure fixed liver blocks are wrapped with a quadruple layer of nylon cloth, and, by squeezing them in a buffer solution, individually dissociated cells pass through the cloth without significant damage. The procedure makes it possible to dissociate liver tissue fixed with modified Karnovsky's fixative, Zamboni's fixative or cacodylate buffered glutaraldehyde. The subsequent compatibility of the single cells obtained with many cytochemical procedures has been confirmed. PMID- 2579480 TI - Rotary-shadowed freeze-fracture replicas: a simple method for the analysis of fracture faces. AB - In rotary-shadowed freeze-fracture replicas, intramembrane particles on the periphery of a membrane fracture face are not uniformly shadowed from all sides. Those eccentrically positioned intramembrane particles with a net centripetally directed shadowing are on a convex fracture face. In contrast, those eccentrically positioned intramembrane particles with a net centrifugally directed shadowing are on a concave fracture face. Centrally positioned intramembrane particles on convex faces are uniformly shadowed from all sides; however, central depressions of concave faces are often unshadowed. PMID- 2579481 TI - An improved Van Gieson. PMID- 2579482 TI - An improved method for transferring semithin epoxy sections from the microtome knife to microscope slides. PMID- 2579483 TI - Staining large epoxy resin embedded histologic sections by a simplified hematoxylin and eosin method using heat. PMID- 2579485 TI - No-cure surgery extends life. PMID- 2579484 TI - A comparative study of DAPI, DIPI, and Hoechst 33258 and 33342 as chromosomal DNA stains. AB - A comparison of four DNA stains considered to be AT-specific with chromosomes from a clonal Chinese hamster cell line B14F28-C5 have been made. The flow karyotype histograms indicate that DAPI, DIPI, and Hoechst 33258 and 33342 do stain similarly in the same preparation. DAPI staining is specific and highly reproducible in this line. We, therefore, recommend this dye as a single chromosome DNA stain for high-resolution flow cytometric measurements in cytogenetics and mutation research. PMID- 2579486 TI - Laser treatment of macular disease: patient and laser selection. PMID- 2579488 TI - Laser treatment of macular disease: procedure and follow-up. PMID- 2579487 TI - Usual and unusual uses of the laser in glaucoma. PMID- 2579489 TI - CO2 laser. PMID- 2579490 TI - Laser treatment of macular disease: recurrence of subretinal neovascular membranes after treatment. PMID- 2579491 TI - Lymphocytotoxic antibodies in leukemic patients treated with bone marrow transplantation. AB - Lymphocytotoxic antibodies were studied sequentially in a series of 42 patients with leukemia who received a bone marrow graft. Of these patients, 38% had cytotoxic antibodies before bone marrow transplantation (BMT). After BMT the antibody status changed with time, but 62% of the patients had antibodies at some time after BMT. During the first 10 weeks after BMT, 40% of the patients had antibodies. Thereafter the frequency rose to 50% and remained at that level beyond one year after BMT. In successful grafts the gamma globulins are of donor origin six months after BMT; thus donor B cells are capable of forming lymphocytotoxic antibodies even when the immune system is suppressed by cyclosporine. The antibodies had recognizable HLA specificity in about half the cases before and after BMT. When donor and patient were HLA-identical, HLA specificity did not correspond to donor/recipient antigens. In two cases in which the donor was matched for only one haplotype, antibodies formed by recipient cells, active against donor HLA antigens, were found. PMID- 2579492 TI - [Effect of levamisole on alpha 2-macroglobulin and lysozyme levels in the trachea, peritoneal exudate and serum of mice]. AB - Levamisole was studied for its effect on alpha 2-macroglobulin and lysozyme content in the blood serum, peritoneal exudate, tracheal extracts of mice. Dynamics of changes in the content of these proteins was studied with its significant increase depending on the methods of the preparation administration (inhalation; intraperitoneal and per os). PMID- 2579494 TI - [Intravital staining with sulfan blue (disulphin blue) in radical surgery of osteomyelitis]. PMID- 2579493 TI - [Biochemical studies of potential-dependent sodium channels]. AB - The data on interaction of sodium channels of excited membranes with various neurotoxin groups are considered in the paper including the data on using biologically active neurotoxin derivatives as a specific label. These derivatives carry fluorescent or photoactive groups possessing high specific radioactivity, which permits developing the methods for sodium channel solubilization and solubilized preparation stabilization. The high-purified preparations are characterized by the methods of gel chromatography, centrifugation within the gradient density, gel electrophoresis and affinity chromatography. Experiments on reconstruction of solubilized preparations in the bilayer of lipid vesicles are under discussion. PMID- 2579495 TI - [Methods of studying the motor and perceptual development of children]. PMID- 2579497 TI - [Micturition status after transvesical adenomectomy and ways of improving it]. PMID- 2579499 TI - Ischemic heart disease in patients with large gland prostatic hypertrophy. AB - Fifty consecutive patients with large gland prostatic hypertrophy, requiring open prostatectomy, were analyzed retrospectively with regard to relationship to the subsequent development of ischemic heart disease. A significant increase in the development of progressive ischemic heart disease and sudden death was found in these patients when compared with two control groups. These findings are analyzed. PMID- 2579498 TI - Prostate cancer: experience with definitive irradiation in the aged. AB - When considering therapeutic options for localized prostate cancer, stage and grade of disease have been the most important determinants. In the elderly, the nominal age has assumed increasing importance in the final decision. A balanced judgment must be reached between the patient's normal life expectancy and the rapidity with which the cancer may be expected to express its malignant potential. By careful attention to patient selection and the details of treatment, definitive irradiation can improve quality of life and survival. Of 63 patients aged seventy-three to ninety years referred for irradiation, 56 were found medically suitable for definitive treatment. A review of our experience is presented. PMID- 2579496 TI - Sexual life following 'minimal' and 'total' transurethral prostatic resection. AB - 81 otherwise healthy men with an average age of 67 years and verified prostatic hypertrophy were randomized into two groups for either 'minimal' or 'total' transurethral prostatic resection (TUR-P). Interviews on sexual life were made preoperatively and 6 and 12 months postoperatively. 58 men (72%) were prior to the operation sexually active. 18 (31%), mainly men of advanced age, discontinued sexual activity following TUR-P. 40 (69%) remained active. 19 had retrograde ejaculation. No significant difference was found between 'minimal' and 'total' TUR-P concerning the effect on sexual activity and the occurrence of retrograde ejaculation. PMID- 2579500 TI - Effect of concentration and time of drug exposure on clonal growth of murine bladder cancer. AB - The use of a tumor colony assay was evaluated for its ability to predict anticancer drug response in an N[4-(5-nitro-2-furyl)-2-thiazolyl] formamide mouse bladder tumor model. One-hour and continuous drug exposure were compared to determine what effect altering drug concentration and time of exposure would have on the predictability of the tumor colony assay in the murine model. Ten anticancer drugs were tested in the murine model, and tumor cells removed from control mice were used for in vitro drug testing. One-hour and continuous drug exposure (using the one-hour drug level) were performed simultaneously and the in vitro and in vivo data compared. Using one-hour drug incubation in the tumor colony assay resulted in a true positive predictive rate of 54 per cent and a true negative predictive rate of 70 per cent. Continuous drug incubation overestimated drug sensitivity resulting in a drop in the predictability of the tumor colony assay. We conclude that using one-hour drug exposure the tumor colony assay is predictive of chemotherapeutic drug response in this murine bladder tumor model. PMID- 2579501 TI - Carcinoma of prostate metastatic to penis. AB - A case report of prostatic carcinoma metastasizing to the penis is presented. Review of the literature revealed only 54 cases reported to date. With survival rates ranging from two to six months, the prognosis is gloomy. The most commonly used method of treatment was local wide excision of the lesion. PMID- 2579502 TI - Prostatic chondroma. AB - The presence of cartilage in the prostate is a rare occurrence and has been reported to be the result of extension from a chondrosarcoma, usually of the symphysis pubis. Also reported has been the occurrence of cartilaginous metaplasia within the prostate. We report herein the occurrence of cartilaginous tissue within the prostate forming a distinct mass of chondroma. To our knowledge this has not been reported previously. PMID- 2579503 TI - Pancreatic endocrine tumours associated with WDHA syndrome. An immunohistochemical and electron microscopic study. AB - Nine pancreatic endocrine tumours of patients with watery diarrhoea hypokalaemia achlorhydria (WDHA) syndrome were examined by immunohistochemistry and electron microscopy. All cases revealed neoplastic proliferation of VIP (vasoactive intestinal peptide)-immunoreactive (IR) cells. Immunoreactivity to a novel peptide hormone PHM-27, which is processed from a common big precursor peptide of VIP (prepro VIP/PHM-27), was identified in VIP-IR cells of 8 tumours. VIP-PHM-IR cells had secretory granules measuring about 130 to 220 nm in diameter. Radioimmunoassay of tumour tissue extracts showed high VIP and PHM contents in proportional amounts in most cases. According to the results of immunostaining, the 8 tumours fell into two large groups; 5 with PP (pancreatic polypeptide)-IR cells and 3 with CT (calcitonin)-IR cells. The former group demonstrated VIP cells and PP cells intermingled in various proportions, including one tumour in which coexistence of PP-IR and VIP-IR in the same cells was demonstrated. Cell heterogeneity of the tumours and possible relationships of VIP, PP and CT cells were discussed. PMID- 2579504 TI - Tumour-associated antigens in mammary and extramammary Paget's disease. AB - The immunoperoxidase technique was used to study the immunoreactivities of two murine monoclonal antibodies to carcinoma-associated antigens raised respectively against a human breast cancer line (MBr1) and an ovarian carcinoma (MOv2) and of a conventional anti-CEA serum in 20 cases of mammary Paget's disease of the nipple and in three cases of extramammary Paget's disease. Each of the immunoreagents stained Paget's cells in a high proportion of cases and failed to discriminate mammary from extramammary disease. The antigenic phenotypes of underlying in situ or infiltrating breast carcinomas corresponded to those of the associated Paget's disease of the nipple. The consistent immunoreactivity of eccrine and apocrine sweat glands and of normal mammary epithelia indicated an antigenic relationship between epithelia of adnexal derivation and Paget's cells. PMID- 2579505 TI - Avian leukosis virus-induced osteopetrosis is associated with the persistent synthesis of viral DNA. AB - DNAs from 19 cases of avian leukosis virus-induced osteopetrosis have been analyzed for viral sequences. Among these were instances of rapid, intermediate, and slow onset osteopetrosis. The DNAs from osteopetrotic bone contained no evidence for osteopetrosis being caused by proviral insertions into or viral transductions of a host protooncogene. Instead, DNAs from osteopetrotic bone displayed evidence for osteopetrosis being associated with the persistent synthesis of viral DNA. Each of the 19 DNAs contained unintegrated as well as integrated viral DNA. Rapid onset osteopetrosis contained about 3X more viral and proviral DNA than intermediate or late onset osteopetrosis. Unintegrated viral DNA could not be detected in DNAs extracted from the bursa bone marrow of osteopetrotic chickens or in DNA extracted from the normal bones of an avian leukosis virus-infected chicken. Thus, the persistent synthesis of unintegrated viral DNA was observed in osteopetrotic but not normal tissues of avian leukosis virus-infected chickens. PMID- 2579506 TI - A rapid screening procedure for the isolation of nonconditional replication mutants of Mason-Pfizer monkey virus: identification of a mutant defective in pol. AB - A rapid, sensitive, and reproducible method for the isolation of human cell clones containing nonconditional, replication-defective (rd) mutants of Mason Pfizer monkey virus (M-PMV), the prototype of the D-type retroviruses is described. The two mutants, rd1 and rd2, thus far isolated have been analyzed for virus particle production (using radiolabeled precursors and by electron microscopy) and for the status of intracellular viral precursors. Thin sections of rd1 and rd2 infected cells showed typical M-PMV particles when observed under electron microscope. A more direct assay of virus production, by labeling the mutant cell clones with [3H]uridine, also showed a distinct virus peak at an approximate density of 1.16 g/ml when culture fluids from rd1 and rd2 were analyzed. Analyses of these two mutants showed no defect in either gag or env gene products, however, further analysis of rd1 showed that the Pr180gag-pol was altered in its migration on SDS-polyacrylamide gel electrophoresis and no reverse transcriptase activity could be detected in rd1 virions. Mutant rd2, on the other hand, assembles noninfectious virus particles that are otherwise indistinguishable from those produced by wild-type cell clones. The biochemical basis for the defect in this mutant remains to be established. PMID- 2579507 TI - [Use of interferon in experimental and clinical oncology based on data from foreign scientific research centers]. PMID- 2579508 TI - [Immunoenzyme method of determining brain-specific alpha 1-globulin in glial tumors]. AB - Specific alpha 1-globulin of the brain was assayed by an immunoenzyme technique in blood sera from cases of various brain pathologies and healthy donors. Relative elevation in brain specific alpha 1-globulin level, as compared with that in healthy subjects, was more frequent in patients with malignant glial tumors of the brain, less frequent in cases of benign glial tumors and in very few patients suffering from other brain diseases. Raised level of specific alpha 1-globulin may be caused by disorders in the blood-brain barrier or lesions in brain or tumor tissues which is peculiar to glial malignancies of the brain. The said test offers much advantage in diagnosis of glial tumors. PMID- 2579509 TI - Endoscopic neodymium-YAG laser treatment of nonresectable gastrointestinal tract cancer. AB - Five patients with advanced gastrointestinal tract cancers were treated endoscopically with the neodymium-YAG infrared laser. Palliative ablation of an obstructing or hemorrhaging intraluminal malignant lesion was safely achieved in all patients. PMID- 2579511 TI - [Immunologic multiple sclerosis research]. AB - In multiple sclerosis (MS) different autoimmunological phenomena can be held responsible for the inflammatory demyelinating process. A cytotoxic reaction of lymphocytes against the encephalitogenic peptide of the myelin basic protein is assumed to be the primary factor; furthermore, demyelinating antibodies play an important part in the destruction of the myelin sheath. As can be identified at the acute stage of the disease, anomalies in the immunoregulation and the suppression of the control mechanism give additional indications towards the immunopathogenesis of MS. The cause of the demyelinating autoimmune process is unknown. According to epidemiological studies, a virus infection is the most likely etiology for MS. PMID- 2579510 TI - [Results of international multiple sclerosis research]. AB - The present state of international multiple sclerosis research is summarized in a diagram on the pathogenesis of multiple sclerosis (MS). Recent epidemiological findings are reviewed, stressing regional increases in the frequency and the lower prevalence rates but more serious manifestation in the far east. Findings on HLA-antigens point to a genetic component. The frequency of DR2/DW2 correlates with the proximity to the disease susceptibility gene on chromosome 6. Diagnostic progress includes the measurement of visual evoked potentials, the results of computer tomography and most recently the nuclear magnetic resonance (NMR) method, which makes it possible to visualize foci earlier and in greater number. The new diagnostic possibilities by analysis of the humoral and cellular response are briefly described. With respect to the therapy of MS it is stressed, that cause-related treatment comprises only a small part of the wide range of therapeutic possibilities. The immunosuppressive treatment with azathioprine, cyclophosphamide and cyclosporin A is discussed, also therapy with interferon and interferon-inductors. Finally, current experiments with hyperbaric oxygenation are mentioned. The essential necessity of systematic research on the pathogenesis of MS as the prerequisite of effective causal therapy is stressed. PMID- 2579512 TI - [Aging changes in conjunctival blood vessels]. AB - The relation of the changes in the conjunctival blood vessels to the age were studied in a group of 217 persons aged 20 to 79 years. All persons suffering from arterial hypertension, diabetes, systemic diseases and manifested forms of arteriosclerosis were excluded. It has been proved that examination of the conjunctival blood vessels by means of the slot-lamp facilitates the study of the changes in the microscopic blood vessels in relation to the age. Most conspicuous was the increase of the meander course of the blood vessels, also the increasing number of blood vessels is more frequent in the group of older persons. Clusters of vessels and a narrowing of the diameter of the arterioles was seen only in persons over fifty years of age. The "upright" course of the arterioles was found only in individual cases and without any special dependence to age. Sacculations on the small veins and microaneurysms on the arterioles were not observed in any of the examined group of healthy persons. PMID- 2579513 TI - [Typical spontaneous changes in heart rate in pheochromocytoma]. AB - Investigations in 13 hospitalized patients with pheochromocytomata showed peculiar characteristics of heart rate variation at rest, when compared with normals. All patients were given alpha- and beta-sympatholytic drugs. In one case alpha-methyl-Tyrosine caused I-II degree AV blocks and a stable high frequency sinus rate without physiological variations. Resting heart rate in pheochromocytoma varied interindividually from 55-105/min, in the absence of clinical attacks of the underlying disease. The frequency profile was characterized in 12 patients by sudden and inadequate rises of heart rate (200%) of short duration, which were often recorded within 20 seconds of the onset of muscular activity. A similar but less pronounced heart rate modulation was found 1-2 weeks after operation in 3 cases. Our observations indicate that the heart rate profile described may be a sensitive parameter of dysfunction of the autonomous nervous system in pheochromocytoma. Whether the heart rate characteristics are of diagnostic value has to be assessed by further studies. PMID- 2579514 TI - [Mitochondrial participation in regulating the transmembrane Ca2+ current within myocardial cells]. PMID- 2579515 TI - [Status of prenatal diagnosis in Switzerland]. AB - In Swiss laboratories of Basel, Berne, Geneva, Lausanne, Locarno and Zurich 19'872 prenatal diagnosis were carried out from 1971 to 1983. The frequency of the tests carried out for the different indications and the numbers of the detected anomalies are presented. In 12'485 tests performed because of advanced maternal age (35 years and older) 241 chromosome anomalies were diagnosed with 125 trisomies 21 among them. In contrast, only 7 trisomies 21 were found in 5'225 samples from women below 35 years. Prevention of Down's syndrome was the prevalent motivation of 93 percent of the pregnant women. Approx. 42 percent of the Swiss women, 35 years and older, requested an amniocentesis in the course of the last few years. Remarkable progress was made in the ultrasound diagnosis of fetal malformations. Developments in the field of first trimester prenatal diagnosis and in the use of DNA technology for the diagnosis of monogenic defects are dealt with. PMID- 2579516 TI - Effects of prenalterol and volume loading with dextran on haemodynamics and oxygen consumption in dogs during high epidural block with special reference to the splanchnic region. AB - High lumbar epidural block was induced in seven dogs, causing a fall in mean arterial blood pressure (AP) from 24.5 +/- 2.9 to 12.0 +/- 3.1 kPa owing to reductions in cardiac output (QT) and systemic vascular resistance (SVR) to 67% and 68% of the pre-epidural values. Volume loading with dextran 10 ml X kg-1 b.w. increased QT nearly to the pre-epidural value. SVR decreased further to 61% of the pre-epidural value and AP was only slightly increased to 14.9 +/- 2.7 kPa. Subsequent administration of prenalterol 20 micrograms X kg-1 b.w. caused a further increase in QT to 17% above the pre-epidural value due to an increase in heart rate of 51 beats/min. AP did not change since SVR decreased further to 49% of the pre-epidural value. The hepatic arterial blood flow (QHA) was essentially unchanged during epidural block as well as during volume loading, while the portal venous blood flow (Qpv) was changed concurrently with (QT). In spite of the decrease in SVR, the preportal and hepatic arterial vascular resistances were not diminished following prenalterol. The increase in OT must therefore have favoured other vascular beds. Hepatic and pre-portal tissue oxygen uptakes were unchanged during the experimental procedure, while whole-body oxygen uptake decreased by 20% following the epidural block and increased nearly to the pre epidural level following volume loading in combination with prenalterol. PMID- 2579517 TI - Immunocytochemical study of myelin-associated glycoprotein (MAG), basic protein (BP), and glial fibrillary acidic protein (GFAP) in chronic relapsing experimental allergic encephalomyelitis (EAE). AB - Chronic relapsing experimental allergic encephalomyelitis (EAE) lesions that resemble those seen in multiple sclerosis (MS) were produced in young Hartley and strain 13 guinea pigs (Lassmann and Wisniewski 1979). To study distributions of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP) in these lesions, paraffin and semithin epon sections of CNS from eight of these guinea pigs were immuno-stained with antisera to these proteins according to the peroxidase-antiperoxidase (PAP) method. In lesions with active myelin sheath breakdown, changes in anti-MAG and anti-BP immunoreactivity corresponded closely. Abnormal and/or decreased anti-MAG staining did not extend beyond margins of lesions into surrounding areas containing myelin sheaths stained normally by anti-BP and by histological stains for myelin. GFAP-stained astrocyte processes were more numerous and much larger in more chronic lesions. Anti-MAG and anti-BP both stained regenerating myelin sheaths which were very numerous in both paraffin and epon sections. In the latter, anti-MAG also stained some myelin-forming oligodendroglia. The results are additional evidence suggesting that in chronic relapsing EAE, myelin sheaths are the primary target. Oligodendroglia appear to be relatively unaffected and remyelinate most of the demyelinated axons. PMID- 2579519 TI - Neuronal intranuclear hyaline inclusion disease presenting as Friedreich's ataxia. AB - A case of neuronal intranuclear hyaline inclusion disease (NIHID) is described, and the literature on seven reported cases is briefly reviewed. The patient was a 24-year-old man who died of a chronic progressive neurologic disease starting at the age of 6 years. Clinically, the disease presented as Friedreichs's ataxia, and pathologically it was characterized by multisystem atrophy. An outstanding feature was the presence of widespread intranuclear hyaline inclusions in neurons of the brain, spinal cord, and myenteric plexus of the gut. The inclusions displayed yellow-green autofluorescence under ultraviolet (UV) light and were filamentous ultrastructurally. It seems that cases bearing such peculiar neuronal inclusions represent a distinct disease entity of unknown origin. The disease, which is sometimes familial, usually starts in childhood and affects both sexes. Clinically, it presents as multisystem degeneration with progressive ataxia as the prominent feature. Pathologically, it is characterized by neuronal loss, fiber tract atrophy, and intranuclear neuronal inclusions. In some cases such inclusions were found also in neurons of the myenteric plexus. Since these are accessible to biopsy it is recommended that rectal biopsy be made in every case of "atypical" system atrophy. PMID- 2579520 TI - A novel 1,4 dihydropyridine, BAY K 8644, with contractile effects on vascular smooth muscle. AB - The effect of a new 1,4-dihydropyridine derivative, methyl-1,4-dihydro-2,6 dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate, BAY K 8644, was studied on isolated thoracic aortae obtained from male Wistar-Kyoto rats. In rat aorta BAY K 8644 had dual actions as the compound induced contractions in the concentration range 10(-8)-10(-5)M and relaxation at higher concentrations. In low concentrations (10(-8)M) BAY K 8644 increased the contractile response to both noradrenaline and potassium and shifted the concentration response curves to the left while in high concentrations BAY K 8644 (10(-4)M) had a relaxant effect on preparations precontracted by potassium. The contractile response to BAY K 8644 was resistant to wash out in drug free medium but was totally abolished in Ca-free medium. Re-addition of Ca restored the contractile response in a concentration dependent manner. BAY K 8644, 10(-6)M, shifted the Ca-concentration response curve in high potassium solution to the left and increased the maximal response. Phentolamine or propranolol had no effect neither on the contractile nor on the relaxant effect of BAY K 8644. The findings suggest that BAY K 8644 acts mainly by increasing the transmembrane influx of Ca in the vascular smooth muscle cells, and that this effect could be opposite to that of nifedipine. However, in high concentrations BAY K 8644 also seems to have a Ca-entry blocking effect. PMID- 2579518 TI - Spinal cord multiple sclerosis lesions in Japanese patients: Schwann cell remyelination occurs in areas that lack glial fibrillary acidic protein (GFAP). AB - To extend earlier observations on Schwann cell remyelination in multiple sclerosis (MS) lesions (Itoyama et al. 1983) we immunostained spinal cord sections from eight Japanese MS patients with antiserum to Po glycoprotein, a major constituent of peripheral nervous system (PNS) myelin, myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP). Spinal cord sections from six of the eight Japanese MS patients contained large clusters of peripheral myelin sheaths with anti-Po immunoreactivity. In lesions found in four of the six patients, thousands of Po-stained PNS myelin sheaths were present. Necrosis was prominent in these lesions which included more than half of the spinal cord's transverse area. The number and density of regenerating myelin sheaths of peripheral origin were much greater than we observed in MS spinal cord lesions of white people (Itoyama et al. 1983). Anti-GFAP immunoreactivity was present in most brain and spinal cord lesions. However, the areas in lesions that contained large groups of PNS myelin sheaths lacked anti-GFAP immunoreactivity. Our data suggest that spinal MS lesions that are large, severely demyelinated, and partially necrotic may contain factors that inhibit fibrous astrogliosis. These factors, other substances in the large lesions and/or the lack of astrocytic scarring could then promote Schwann cell invasion, multiplication, and remyelination of surviving axons. PMID- 2579521 TI - Intrathecal morphine induces myoclonic seizures in the rat. AB - The development of myoclonic activity as a toxic effect of morphine application into the intrathecal space in rats is described. This syndrome resembled the human syndrome of action myoclonus by its spontaneous onset and its augmentation by initiation of movement or by an acoustic stimulus. It was not reversed or prevented by naloxone. This effect of morphine was associated with an increase in serotonergic activity in the spinal cord and was reduced by pretreatment with parachlorophenylalanine in doses which reduced spinal 5-HT by approximately 60%. The dose which produced this syndrome was about ten times higher than the analgesic dose applied by the same route. Other commonly used opiates such as: methadone (0.5-2 mg/kg), pethidine (2-10 mg/kg), fentanyl (2-10 micrograms/kg) and ketamine (2-10 mg/kg) did not produce myoclonic-like activity, but methadone and pethidine at the highest doses caused respiratory arrest. Fentanyl appeared to be the safest of the drugs tested since a relatively high dose, administered into the intrathecal space did not cause any side effects, while morphine was least safe of the five drugs since it produced myoclonic activity in addition to the widely documented respiratory depression. We suggest that the production of the myoclonic activity is mediated by spinal serotonergic systems. PMID- 2579522 TI - Selective killing of respiratory sufficient yeast cells by paraquat. PMID- 2579523 TI - Influence of penicillin and nalidixic acid on growth and cell division of Escherichia coli K-12. AB - Ultrastructure of E. coli K-12 cells and the synthesis of DNA in bacteria treated with low concentration of nalidixic acid and penicillin was investigated. In E. coli both drugs caused inhibition of cell division in period D of the life cycle although nalidixic acid inhibits division at an earlier stage of septum formation. The ability of cells to form filaments in the presence of nalidixic acid depends on their age, i.e. time at which cells are taken from synchronous culture. PMID- 2579525 TI - Cellulases of Trichoderma longibrachiatum mutants. PMID- 2579524 TI - The effect of proteases on the synthesis of glucoamylase by mutants of Aspergillus niger C. AB - Out of 1230 cultures grown from conidia of the strain Aspergillus niger C, which were previously treated with mutagens, 6 mutants were selected, 5 of which were characterized by considerably lower or lack of proteolytic activity than the parent strain. It was observed that glucoamylase activity and protein synthesis in the mutants examined were directly proportional to the rate of their proteolytic activity. From electrophoretic analysis it was found that in some protease-free mutants or with strongly reduced activity of this enzyme one or two glucoamylase fractions out of four occurring in the parent strain were absent. PMID- 2579526 TI - Studies on the stability of t mutant of influenza virus. AB - The t 30 degrees C mutant of A Port Chalmers 1/73 (H3N2) influenza virus passaged in cotton rats was reisolated. The original mutant and the reisolated virus were compared, the following parameters being tested: NA activity, HA titer, sensitivity of NA and HA to proteolytic enzymes, detergents and temperature, and Michaelis constant of NA. No differences were found in the parameters tested, thus suggesting that features of the mutant remained stable after passage in the susceptible animal organism. PMID- 2579527 TI - Properties of Bacteroides fragilis antigens with specificity B. AB - Five different serologically active preparations were extracted from Bacteroides ovatus ATCC 8483 strain. These substances and sixteen preparations of culture supernatants all giving a positive reaction with antiserum of serotype B were used as inhibitors in haemagglutination inhibition test. The results showed that substances obtained from the culture supernatants differ from endotoxin of Bacteroides ovatus ATCC 8483 serotype B. PMID- 2579528 TI - Autolysis of Caulobacter crescentus grown in the presence of glycine. AB - Caulobacter crescentus was grown in complex medium supplemented with low (0.05%) concentration of glycine, a component of the murein peptide side chains of this bacterium. Murein synthesized in the presence of glycine was poorly crosslinked and the rate of its synthesis was slowed down compared to the control cells. The glycine-grown cells were considerably more sensitive to the chelating agent EDTA and Tris buffer than the control cells and also lysed faster when incubated with beta-lactam antibiotics. No changes in phospholipid composition in the presence of glycine were observed and the outer membrane protein composition of the glycine-grown cells was altered only in the amount of 130 000 protein which forms the surface array of C. crescentus. The effects of glycine can thus be tentatively put down to the reduced crosslinkage of murein synthesized in its presence. PMID- 2579529 TI - Adherence of Candida to mucosal epithelial cells. AB - Adherence abilities of 45 Candida strains to human buccal and vaginal epithelial cells in vitro were tested in two media: 0.9% saline and phosphate buffer. Candida albicans cells adhered more strongly to epithelial cells than fungal cells of other Candida species. These findings were statistically significant according to Mann-Whitney's "U" test with buccal epothelial cells in both of the test media and with vaginal cells in saline only. PMID- 2579530 TI - Free amino acids production by ectomycorrhizal fungi of pine (Pinus sylvestris L.). AB - Studies on free amino acids production by five species of ectomycorrhizal fungi (Amanita muscaria, Suillus granulatus, Suillus luteus, Suillus bovinus and Rhizopogon luteolus) show that all the fungi produced mainly: glutamic acid, leucine, lysine, ornithine, arginine and an unidentified ninhydrin-positive compound X3. Both the quality and quantity of amino acids released was different in the fungal species studied. The predominant amino acids in post-culture liquids in general did not exceed 1.5 micrograms/mg dry mass. PMID- 2579531 TI - Quantitative selection of denitrifying bacteria in continuous cultures and requirement for organic carbon. I. Starch. AB - A mixed population of bacteria from bottom sludge of nitrogen wastewater reservoir was incubated in continuous culture in medium containing 1000 mg nitrate nitrogen/l and starch. Maximal efficiency of denitrification was 5 mg N/l/h. Marked changes in participation of denitrifying bacteria (16-76%) among total number of bacteria was observed, this being dependent on the ratio of starch concentration (CS) to nitrogen concentration (CN) in the medium. The optimal CS/CN ratio ensuring highest participation of denitrifying bacteria was 3.2. The amount of starch required for the denitrification of a defined quantity of nitrogen is negatively correlated (r = -0.98) with the frequency of the occurrence of denitrifying bacteria (XD) and is: CS = (5.53-0.028XD) CN. The denitrifying bacteria in continuous culture were dominated, depending on CS/CN ratio and flow rate of medium, by Alcaligenes faecalis, Paracoccus denitrificans or Pseudomonas mendocina, that is species unable to hydrolyse starch. PMID- 2579532 TI - Naturally occurring chromosomal gene transfer in Thiobacillus versutus. PMID- 2579533 TI - Chemical, experimental, and clinical studies on endogenous ouabain-like substance in hypertension. AB - A heat-stable, low molecular weight, anionic substance(s) capable of inhibiting 3H-ouabain binding and Na+-K+-ATPase activity could be extracted from human urine and plasma. The level of the inhibitor was elevated in 40%-50% of essential hypertensives, compared to controls, and also in some of the offspring of hypertensive parents. Higher levels of the inhibitor were measured in patients treated with beta-blocking agents than in those treated with diuretics. The inhibitor extracted from plasma also appeared capable of (1) inhibiting the uptake of serotonin in human platelets, an Na+-dependent mechanism, and (2) inducing an increase in blood pressure when injected intracerebroventricularly. From these various data, we propose that the increase in the endogenous inhibitor may play a role in essential hypertension and may modulate, at least partially, some of the various cell functions that depend on a transmembrane Na+ gradient, including cellular excitability. PMID- 2579534 TI - Calcium flux regulation in myocardial and vascular smooth muscle. PMID- 2579536 TI - Na-K-ATPase: general considerations, role and regulation in the kidney. PMID- 2579535 TI - Calcium, parathyroid hormone, and hypertension. AB - Both calcium and parathyroid hormone appear to be involved in the acute and chronic regulation of arterial pressure in experimental animals and humans. While the direct evidence is still preliminary, the net effect of calcium and parathyroid hormone under normal physiologic conditions is to favor a reduction in blood pressure. The implications of this assessment for common medical disorders, such as essential hypertension, and less common but oftentimes more challenging clinical conditions, such as end-stage renal disease, are potentially substantial. PMID- 2579537 TI - Effects of loading conditions and contractile state (methoxamine and dobutamine) on left ventricular early diastolic function in normal subjects. AB - The influence of changes in preload, afterload and contractile state on left ventricular (LV) filling characteristics were examined. Normal subjects underwent echocardiographic determination of the peak rates of LV dimension change and wall thinning and their respective timing at rest, after preload augmentation with dextran, during increased afterload with methoxamine and during inotropic stimulation by dobutamine. These 2 peak velocities and their timing in diastole correlated well with each other and responded similarly to interventions. Increased preload resulted in higher peak velocities of dimension change and wall thinning, without changing the time in diastole at which they occur. Both peak velocities moved later into diastole with higher afterload; however, the overall change in magnitude was variable and without statistical significance. Inotropic stimulation resulted in faster rates of peak dimension change and wall thinning, which occurred at an earlier point in diastole. Examination of various measures of LV size and function over a wide range of preload and afterload conditions under a constant contractile state revealed a complex set of relations. The ratio of wall thickness-to-dimension at end-diastole showed the most significant relation to the peak rate of dimension change, whereas peak thinning was best correlated with fractional wall thickening. Both velocities were also significantly but more weakly related to other variables of systolic function. The timing of these peak velocities correlated most closely with the end-systolic wall stress and heart rate. Thus, LV filling and wall thinning depend in a complex fashion on loading conditions, heart rate and contractile state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579538 TI - Endothelial mitosis during the initial stages of corpus luteum neovascularization in the cycling adult rat. AB - The initial stages of neovascularization of the corpus luteum were studied in cycling adult rats using light-microscopic autoradiography. The aim of this analysis was to determine whether endothelial mitosis is a factor in this vascular growth and whether there are differences in the amount of mitotic activity in various regions of the ovary. Ovaries were examined at two time intervals: 1-2 hr and 7-8 hr following ovulation. Animals received an intraperitoneal injection of tritiated-thymidine 20 min prior to perfusion fixation of the ovaries. Autoradiographic demonstration of tritiated-thymidine labeling in endothelial nuclei was considered an indication of DNA synthesis preceding mitosis. The percentage of labeled endothelial cells in the ovaries at both time intervals varied according to the region of tissue examined and the stage of differentiation of that region. Stromal vessels were less heavily labeled than thecal vessels. Thecal vessels surrounding growing follicles were more heavily labeled than those surrounding atretic follicles. The heaviest labeling was seen in the developing corpora lutea 7-8 hr following ovulation. Minimal labeling was evident in the corpora lutea which were formed in previous cycles. A regional difference was also detected in the ovarian mesothelium. The portion of the mesothelium overlying ovulated follicles and developing corpora lutea had the greatest percentage of labeled cells. The major findings of this study were: endothelial mitosis was elevated in the initial stages of luteal neovascularization; the heightened endothelial labeling was confined to specific regions of the ovary; and mesothelium in close proximity to the developing corpora lutea also displayed heightened DNA synthesis. PMID- 2579539 TI - Dietary fiber in pancreatic disease: effect of high fiber diet on fat malabsorption in pancreatic insufficiency and in vitro study of the interaction of dietary fiber with pancreatic enzymes. AB - The effect of high fiber diet on fat malabsorption was evaluated in twelve patients with exocrine pancreatic insufficiency secondary to chronic alcoholic pancreatitis. Additionally, the effect of dietary fiber on pancreatic enzymes was examined in vitro, employing different concentrations of cellulose, pectin, and wheat bran incubated with amylase, lipase, and trypsin. Ingestion of a high fiber diet was associated with a small but significant (p less than 0.01) increase in fecal weight and fecal fat excretion. All patients complained of increased abdominal flatulence with high fiber diet, however, no significant increase in frequency of bowel movements was noted. In vitro studies demonstrated reduction in pancreatic enzyme activity by increasing concentration of dietary fiber and its components. These data suggest that steatorrhea may be enhanced with the ingestion of high fiber diet in patients with exocrine pancreatic insufficiency on oral pancreatic enzyme therapy. Increase in fecal fat excretion may, in part, be related to reduction in the activity of pancreatic enzymes by the dietary fiber. PMID- 2579540 TI - ABH blood group isoantigen expression in breast carcinomas--an immunohistochemical evaluation using monoclonal antibodies. AB - The ABH blood group isoantigen status of a retrospective series of 233 invasive breast carcinomas was examined, employing monoclonal antibodies (MCAB) against A, B, and H antigens with the avidin-biotin-peroxidase complex method. In addition, the H antigen was localized with Ulex Europeus Agglutinin I (UEAI) binding. The MCABs provided consistent and specific staining of erythrocytes and endothelium, as well as normal and neoplastic breast epithelium. The anti-H MCAB yielded cleaner background and less intense staining, but otherwise the staining distribution was comparable to the UEA I technique. Contrary to previous reports, deletion of isoantigen expression was not universal in all invasive carcinomas. Whereas 64%, 77%, and 73% of carcinomas from groups A, B, and AB patients, respectively, demonstrated total isoantigen loss, the remaining tumors exhibited variable degrees of isoantigen expression. Moreover, those carcinomas with complete loss of A and B determinants still displayed variable degrees of H immunoreactivity. Carcinomas from group O patients had different degrees of H antigen deletion, with only 12% showing total loss. Statistical analysis revealed that the isoantigen status bore no significant relationship to various epidemiologic, clinical, and pathologic parameters and did not serve as a useful prognostic determinant. PMID- 2579541 TI - Nasopharyngeal carcinoma: antikeratin immunohistochemistry and electron microscopy. AB - Eighteen examples of nasopharyngeal carcinoma (NPC), a tumor with potential diagnostic difficulty, were studied retrospectively. Using the WHO classification, 16 cases were undifferentiated carcinoma (UC). Immunohistochemistry for each tumor was performed on paraffin sections using two commercially available polyclonal antisera and a monoclonal antibody, AE-1. Method 1 used trypsinization, overnight incubation with the primary antibody and the avidin-biotin complex (ABC) technic. Method 2 used a 20-minute incubation with the primary antibody without trypsinization and employed the peroxidase antiperoxidase (PAP) technic. Method 2 is the one most frequently employed by pathologists who use immunohistochemistry as a diagnostic aid. Method 1 gave clear positive results in each case with antibody AE-1 and, in most cases, with the polyclonal antisera. Electron microscopy in 10 cases demonstrated desmosomes in each case and easily demonstrable tonofilaments in five. The results of this study indicate that in the diagnosis of UC, the most common variant of NPC, squamous differentiation can be documented readily by electron microscopy and immunohistochemistry for keratin proteins. With the latter, optimization of technic is essential for reliable results. PMID- 2579542 TI - A method for the covalent attachment of cells to glass slides for use in immunohistochemical assays. AB - A method for covalently attaching viable cells to glass slides is described. The cells are linked covalently to the slide without the use of drying or other fixation procedures that normally destroy cellular surface antigens. The attachment is permanent, and the slides with attached cells may be cryopreserved. The use of the avidin-biotin-peroxidase procedure with this procedure shows excellent sensitivity comparable to flow cytometry. PMID- 2579543 TI - Follow-up of infants receiving cranial ultrasound for intracranial hemorrhage. AB - Intracranial hemorrhage (ICH) was detected in 38 preterm neonates, using cranial ultrasonic (US) scanning. Forty-three preterm neonates examined during the same period but who had no cranial US evidence of ICH were also identified. Neurodevelopmental follow-up was performed at a mean age of 22.3 months on these 81 children. As a group, children with ICH demonstrated developmental indexes in the normal range but about ten points lower than children without ICH. The outcome in survivors of grade III ICH was quite similar to the outcome in survivors of grades I and II ICH. Survivors of grade IV (intraparenchymal) hemorrhage had a worse outcome. Cerebral palsy was significantly more prevalent in children with ICH. Only two thirds of children without ICH had a completely normal outcome, reinforcing the concept that factors other than ICH alone contribute to neurodevelopmental morbidity in this population. PMID- 2579544 TI - Seizures in children with meningomyelocele. AB - The charts of 111 children with meningomyelocele were reviewed. Ninety-eight had shunted hydrocephalus. Twenty-five of 111 children (24 of 98 children with shunts) had seizures. Age at onset and type of seizure varied. Brain malformation (other than Arnold-Chiari), shunt infection, and perhaps number of shunt revisions were important risk factors in seizure development. The children with seizures were more likely to be developmentally delayed. PMID- 2579545 TI - Idiotypic--anti-idiotypic interactions in man. PMID- 2579546 TI - Changes in plasma haptoglobin and alpha-2-macroglobulin in hemophiliacs receiving factor replacement therapy. AB - Plasma proteins were studied in 84 patients with hemophilia A, who were receiving factor replacement therapy. Compared with age-matched controls, 63 patients (75%) had subnormal haptoglobin and 58 (69%) had elevated alpha-2-macroglobulin. Causes for depressed haptoglobin were sought by correlating ABO blood types, liver function tests, factor VIII procoagulant levels, and intensity of yearly exposure to clotting factor products. Subnormal haptoglobin levels in chronically transfused patients may relate in part to hemolysis from AB incompatability. However, depressed haptoglobin levels were also found in group O hemophiliacs without other evidence of hemolysis. Most patients lacked evidence of active liver disease, making synthetic deficiency unlikely. There was close correlation between depressed haptoglobin and severity of clotting factor deficiency. The degree of alpha-2-macroglobulin elevation correlated with severity of procoagulant deficiency but not with intensity of clotting factor replacement therapy. Since alpha-2-macroglobulin plays a major role in the catabolism of fibrinogen, elevated levels may represent a compensatory increase in response to exogenous fibrinogen contained in the clotting factor concentrates. Alternatively, since alpha-2-macroglobulin has potent immunosuppressive properties, the elevation may represent a response to transfused alloantigens. Whatever the underlying cause, it is likely the elevations are due to endogenous production rather than to transfusions since clotting factor concentrates contain minimal amounts of alpha-2-macroglobulin. PMID- 2579547 TI - -G gamma A gamma-Thalassemia and gamma-chain variants in Chinese newborn babies. AB - The occurrence of gamma-chain abnormal hemoglobins and of gamma-thalassemia in Chinese newborns was evaluated through analyses of the Hb F of over 1,100 babies and of the DNA from one baby and his parents. Gene mapping data identified this baby as a homozygote for -G gamma A gamma-thalassemia, which is caused by a deletion of about 5 kb due to an unequal crossing-over between the -G gamma- and A gamma- genes. This condition is the same as that observed in Indian and Japanese babies [2,3]. Its gene frequency among babies from the Shanghai area was 0.012. A previously unrecognized G gamma chain variant, Hb F-Shanghai or alpha 2 G gamma 266(E10)Lys----Arg, was observed in one newborn. This variant was not detected by conventional techniques but only by high performance liquid chromatography, as the G gamma 66 Lys and G gamma 66 Arg chains had slightly different chromatographic mobilities. Lys at position gamma 66 participates in contacts with the heme group, and its substitution by another amino acid residue might interfere with physiochemical and/or functional properties. No other gamma chain variants have been detected except the well-known A gamma T or F-Sardinia chain (f.A gamma T = 0.076). PMID- 2579548 TI - Tetrahydrouridine, cytidine analogues, and hemoglobin F. AB - 5-Azacytidine (azaC) has previously been shown to raise Hb F levels in the repeatedly phlebotomized baboon (PCV: around 20%). The administration of tetrahydrouridine (THU), an inhibitor of the enzymatic conversion of azaC to 5 azauridine, made it possible to reduce the amount of azaC and also of 2-deoxy-5 azacytidine (d-azaC) by more than 90% and still achieve maximal Hb F elevations. However, the granulocytopenia, usually occurring after 5-azaC, was not altered by the lowering of the dosages in the presence of THU. Thus, the granulocytopenia is not due to 5-azauridine or other catabolic products resulting from deamination. It is also unlikely that it is caused by a direct influence of azaC on RNA since d-azaC also causes granulocytopenia. The persistence of reticulocytosis throughout the treatment with azaC or d-azaC makes it appear likely that the observed increase in Hb F levels to more than 60% of total hemoglobin is not due to a cytotoxic effect on erythropoiesis resulting in a shift of cell populations toward greater immaturity, but to a direct influence of the drug on the regulation of gamma globin chain production. PMID- 2579549 TI - Natural killer cells--toward clinical application. AB - Natural killer (NK) cells are non-B, non-T lymphoid cells of uncertain lineage that rapidly recognize and lyse a large variety of tumor or virus-infected cells, without the need for either prior sensitization or major histocompatibility complex (MHC)-dependent recognition. Though some essential problems in understanding NK cell function are still unsolved, considerable progress has been achieved in recent years following the identification of the characteristic large granular lymphocyte (LGL) morphology of NK cells and their purification, the study of their function at the single-cell level, and the cloning of mouse and human NK cell lines. Activated mainly by interferon (IFN), as well as important producers of IFN, NK cells appear to have a distinct role in immunoregulation in addition to their postulated major role in "immune surveillance," for which convincing in vivo data has accumulated. Future clinical applications may therefore include manipulations of the NK system through expansion and activation of patient's LGL or the use of cloned human NK cell lines. PMID- 2579551 TI - Prognostic factors in patients with hepatocellular carcinoma receiving systemic chemotherapy. Identification of two groups of patients with prospects for prolonged survival. AB - Among 37 patients with hepatocellular carcinoma given systemic chemotherapy, 12 (32 percent) lived 14 to 37 months from initiation of treatment whereas the remainder died within five months. Individual factors associated with improved survival included fully ambulatory performance status, lack of jaundice, response to chemotherapy, the fibrolamellar carcinoma pathologic variant, absence of cirrhosis, and normal serum alpha-fetoprotein levels. Patients living longer than 12 months fell into two groups. Seven patients with fibrolamellar carcinoma lacked evidence of hepatitis B serum markers or cirrhosis and had normal alpha fetoprotein levels and surprisingly frequent extrahepatic metastases. All but one were Caucasians aged 25 years or less. The other five "long-term" survivors were all fully ambulatory without jaundice, and the majority were older non-Caucasians with tumor confined to the liver at the time of diagnosis and with hepatitis B markers, elevated alpha-fetoprotein levels, or cirrhosis. All patients without fibrolamellar carcinoma who were less than fully ambulatory or who had jaundice died quickly. Patients with fibrolamellar carcinoma have homogeneous clinical features, and their disease follows a relatively indolent course. In other patients with hepatocellular carcinoma, assessment of ambulatory status and serum bilirubin determination can identify those with some prospect of prolonged survival. PMID- 2579550 TI - The effect of methionine and 5-azacytidine on fragile X expression. AB - The cellular mechanism for the expression of the fragile site at Xq28 is unknown. We tested the effect of 5-azacytidine and methionine on fragile X expression in lymphocytes and lymphoblastoid cells in an attempt to determine if DNA methylation was involved. We were unable to demonstrate a consistent dosage effect of methionine on fragile X expression. While 5-azacytidine was found to inhibit the fragile X in both males and females, it did so only at relatively high concentrations. We conclude that the role, if any, of DNA methylation in fragile X expression is likely to be secondary, the primary effect being due to thymidylate depletion. PMID- 2579552 TI - Pseudogout presenting with low synovial fluid glucose: identification of crystals by gram stain. AB - A man developed acute monoarticular ankle arthritis caused by calcium pyrophosphate dihydrate (CPPD) crystals. The clinical syndrome resembled that of a pyogenic arthritis. Synovial fluid analysis revealed a glucose concentration of 13 mg/dL and 99,000 white blood cells/mm3. Only one other report of an extremely low synovial fluid glucose associated with pseudogout could be found. The diagnosis of pseudogout was initially suggested when rhomboidal forms were seen during synovial fluid Gram stain examination. Synovial fluid examination with polarized microscopy was initially negative, but revealed numerous CPPD crystals when repeated on the third hospital day. This case serves to illustrate how pseudogout can mimic pyogenic arthritis in both clinical presentation and low synovial fluid glucose concentration. The examination of Gram-stained synovial fluid can reveal the rhomboidal forms of CPPD crystals. The appearance of these crystals is documented in this report. PMID- 2579553 TI - The spectrum of mastocytosis. AB - Mastocytosis represents a spectrum of clinical disorders that results from an aberrant proliferation of tissue mast cells. This disease process may be confined to the skin (cutaneous mastocytosis) or may involve multiple organs (systemic mastocytosis). Parameters that are useful in differentiating cutaneous from systemic disorders include patient age, symptom complex, and clinical signs. A wide range of clinical symptoms may be encountered in patients with mastocytosis which result from the release of pharmacologically potent mast cell mediators. Distinct cutaneous patterns resulting from skin mast cell infiltrates can be helpful in identifying patients with systemic involvement. The diagnosis of mastocytosis is confirmed by demonstrating increased tissue mast cells in involved organs. The overall prognosis for patients with proliferative mast cell disease is relatively good, although a small percentage are at risk for developing a fatal neoplastic disorder (malignant mastocytosis). Treatment of mastocytosis is directed at both inhibiting mast cell degranulation and blocking the potential systemic effects of released secretory products. Future therapeutic advances depend upon an improved understanding of the basic mechanisms involved in mast cell mediator release and the forces that govern mast cell growth and development. PMID- 2579554 TI - Brief clinical report: interstitial deletion of the long arm of chromosome 10: del(10)(q11.2q21). AB - A de novo interstitial deletion of part of the long arm of chromosome 10 [del(10)(q11.2q21)] was identified by GTG (G-bands by trypsin using Giemsa) banding in a 9-year-old girl with mental retardation and minor anomalies. Only one other case of a similar deletion has been reported [Ray et al, 1980] and the phenotypic findings of the two cases are compared. PMID- 2579555 TI - Marker chromosomes: cytogenetic characterization and implications for prenatal diagnosis. AB - Satellited marker chromosomes were identified in four individuals from unrelated families; one was first encountered in cultured amniotic fluid cells obtained for prenatal diagnostic studies. We present cytogenetic characterization of these marker chromosomes and clinical findings in the individuals carrying them. Identification of a marker chromosome in amniotic fluid cell cultures presents problems in genetic counseling, as it is often difficult to determine the clinical significance of such a finding. Chromosome-banding techniques now allow the precise identification of satellited marker chromosomes originating from chromosome 15. Presence of a supernumerary bisatellited der(15) marker chromosome containing the proximal long arm of 15 has been associated with mental and developmental retardation. Application of chromosome-banding techniques was useful in characterization of the marker chromosomes and providing prenatal genetic counseling. PMID- 2579556 TI - The centralized prenatal genetics screening program of New York City III: The first 7,000 cases. AB - The Prenatal Diagnosis Laboratory of New York City (PDL) is a regional program for the prevention of genetic diseases. The administrative aspects of the establishment of the laboratory were described in papers I [Hsu, 1981] and II [Hsu and Benn, 1981] in this series. We now report our experience of the first 7,000 referrals to the laboratory. The laboratory achieved a success rate of 99.5% in obtaining a diagnosis. The frequency with which a repeat amniocentesis was required was 1.9%, usually attributable to inadequate initial amniotic fluid volume or condition. Cases were completed in an average time of 20.82 days. A total of 149 (2.13%) cytogenetic abnormalities were detected. There were 59 nonmosaic autosomal trisomies and 29 sex chromosome abnormalities. The incidence of unbalanced structural abnormalities (0.186%) was much higher than that reported in surveys of newborn infants largely because of the prenatal detection of cases with supernumerary chromosomes. The incidence of balanced structural abnormalities was also considerably higher than that found in surveys of the newborn population, in part because of the detection of subtle familial pericentric inversions of common chromosome regions (inv(Y)(p11q11), inv(2) (p11q13), and inv(1)(p11q13)). The incidence of cases with multiple independent chromosome abnormalities was no higher than expected by chance. A high incidence of mosaicism, pseudomosaicism, and maternal cell contamination was found. Screening for neural tube defects accounted for the detection of a further 16 abnormalities. Nearly all women with severely abnormal fetuses (trisomy 13, 18, 21) elected to terminate their pregnancy whereas only 62% of patients with a prenatally diagnosed sex chromosome abnormality elected to terminate their pregnancies. Full details of follow-up and confirmatory studies for unusual diagnoses are reported. Utilization of prenatal diagnosis in the New York City area has increased sharply since PDL became operational. The laboratory's success illustrates the role of a prenatal diagnosis laboratory that provides a service independent of the patient's financial status. The experience further shows the high degree of acceptance of prenatal diagnosis by individuals at high risk for a child with a genetic disorder. PMID- 2579557 TI - Cardiac reactivity and adaptive behavior. AB - The relationship between adaptive behavioral function and cardiac reactivity to auditory, somatosensory, and visual stimuli was evaluated using a heterogeneous population of developmentally disabled infants and young children. Stimuli of all sensory modalities resulted predominantly in a cardiac deceleration, and the magnitude of these responses varied systematically between subjects. A multiple regression analysis revealed that 60% of the variance in adaptive behavior, as measured by the Adaptive Behavior Scale for Infants and Early Childhood, could be accounted for by age and the cardiac responses. The factor with the greatest predictive weighting was cardiac reactivity to a vibrotactile stimulus, which showed a correlation of .65 with adaptive behavior scores. PMID- 2579558 TI - Retention of symbolic communications skills by severely mentally retarded persons. AB - The nonspeech symbol vocabularies of five severely mentally retarded persons were assessed 18 months after the completion of a longitudinal computer-keyboard symbol acquisition study. These individuals retained a mean of 83% of their comprehension vocabularies and 70% of their production vocabularies without systematic maintenance teaching on the learned symbols. Interviews with special education and living unit staff members corroborated this result and described the ways in which the subjects used their conversation boards in their everyday environment. PMID- 2579559 TI - Erythrocyte concentrations and transmembrane fluxes of sodium and potassium and biochemical measurements during the menstrual cycle in normal women. AB - The erythrocyte concentrations and the transmembrane fluxes of sodium and potassium were investigated in 20 normal women during the two stages of the menstrual cycle. Half of the women were using oral contraceptives and the other half were not. In women with a normal menstrual cycle the erythrocyte sodium concentration and the ouabain-insensitive total potassium efflux were lower in the luteal than in the follicular phase. Intracellular potassium concentration, ouabain-sensitive rubidium 86 uptake and the furosemide-sensitive sodium and potassium efflux did not differ significantly between the two periods of the cycle. No cycle-related variation in sodium or potassium intracellular concentration was observed in women using oral contraceptives. In these women, however, the ouabain-sensitive 86Rb uptake was increased in the second part of the menstrual cycle. In each woman with a normal menstrual cycle the plasma progesterone, renin activity, angiotensin II, plasma aldosterone concentration, and urinary aldosterone excretion increased during the luteal phase. The increment in the plasma renin activity, plasma angiotensin II, and plasma and urinary aldosterone indicate a stimulation of the renin-aldosterone axis in this menstrual period. During the same phase, serum cholesterol was decreased significantly. When the women using oral contraceptives were compared to those not using them, the renin-aldosterone axis was already stimulated during the first part of the cycle; no further stimulation occurred during the second part. PMID- 2579561 TI - Shoulder pain in hemiplegia. AB - Development of a painful shoulder in the hemiplegic patient is a significant and serious problem, because it can limit the patient's ability to reach his or her maximum functional potential. Several etiologies of shoulder pain have been identified, such as immobilization of the upper extremity, trauma to the joint structures, including brachial plexus injuries, and subluxation of the gleno humeral joint. A review of the literature explains the basic anatomy and kinesiology of the shoulder complex, the various etiologies of hemiplegic shoulder pain, and the pros and cons of specific treatment techniques. This knowledge is essential for the occupational therapist to evaluate effectively techniques used to treat the patient with hemiplegic shoulder pain. More effective management of this problem will facilitate the patient's ability to reach his or her maximum functional potential. PMID- 2579560 TI - Correlation of choroidal subretinal neovascularization with fluorescein angiography. PMID- 2579562 TI - The width of the attached gingiva during orthodontic treatment: a clinical study in human patients. AB - Studies of the influence of orthodontic movement on the width of the attached gingiva gave conflicting results. Therefore, it was decided to evaluate this parameter in human patients during a full orthodontic movement with fixed appliances. Retrusion of six maxillary anterior teeth was performed in thirteen patients scheduled in a prophylactic program that included a 2-week recall during the entire experiment. Before and after treatment the plaque index, the sulcus bleeding index, the width of the keratinized and the attached gingiva, and the marginal gingiva mobility index were measured. The results indicated that retrusion of the maxillary anterior teeth had no influence on any of the measured parameters. PMID- 2579564 TI - Objective changes in trypsin, alpha 1-antitrypsin, and alpha 2-macroglobulin values as a result of sodium fluoride treatment in patients with otosclerosis. PMID- 2579563 TI - Localization of a membrane glycoprotein in benign fibrocystic disease and infiltrating duct carcinomas of the human breast with the use of a monoclonal antibody to guinea pig milk fat globule membrane. AB - With monoclonal antibody D-274, raised against guinea pig milk fat globule membrane, the distribution of mucinlike glycoproteins of Mrs greater than or equal to 400,000 was determined in benign fibrocystic disease and infiltrating duct carcinoma of the human breast. These glycoproteins, called collectively PAS I, were detected in 19 out of 20 cases of benign fibrocystic disease and in at least 26 out of 47 cases of infiltrating duct carcinoma. PAS-I was concentrated on luminal surfaces of ducts and alveoli in morphologically differentiated regions of the tumors. In areas where the glandular nature of the tissue was less evident in infiltrating duct carcinoma, the PAS-I determinant recognized by antibody D-274 was present on irregular luminal surfaces and in the cytoplasm. There was a negative correlation between the short-term recurrence (less than 2 years) of infiltrating duct carcinoma and the detection of strong positive staining with antibody D-274. The results are discussed with reference to recent studies on PAS-I in human breast tissue using monoclonal antibodies raised against human milk fat globule membrane. PMID- 2579565 TI - Clinical studies on fluoride in otospongiosis. PMID- 2579566 TI - Na-Ca exchange: stoichiometry and electrogenicity. AB - This review discusses the evidence concerning the stoichiometry of Na-Ca exchange. In particular we consider whether the Na-Ca exchange has been shown to transport more than two Na+ ions per Ca2+ ion and therefore whether it generates an electric current. The first part of this review discusses both direct and indirect evidence concerning the stoichiometry of the exchange and its possible voltage dependence. We find that, although there is some evidence suggesting that more than two Na+ ions may exchange for each Ca2+ ion, most of the available evidence is equivocal and cannot fix the stoichiometry precisely. Furthermore, using a simple and explicit circulating carrier model for the Na-Ca exchange, we show that the effect of membrane potential on the Na-Ca exchange may be considerably more complicated than is generally believed. In particular we find that both electrogenic and electroneutral exchanges will be affected by membrane potential. We therefore conclude that the demonstration of the voltage dependence of the Na-Ca exchange does not necessarily imply that it is electrogenic. Additionally, this analysis shows that, apart from a restricted range near thermodynamic equilibrium, it is impossible to predict either the magnitude or the direction of the effects of membrane potential on the exchange. In the second part of the review we consider whether any known membrane currents may be attributed to Na-Ca exchange. We show, in contrast to previous suggestions, that the Na-Ca exchange can theoretically produce a current that appears to be activated by intracellular Ca and that has a reversal potential. However, the experimental demonstration that a given current is produced by Na-Ca exchange is hampered by the existence of other Ca- and Na-dependent currents. In conclusion, we feel that there is no evidence that allows any particular membrane current to be unambiguously identified with the Na-Ca exchange. PMID- 2579567 TI - Inositol trisphosphate and diacylglycerol as intracellular second messengers in liver. AB - Receptor occupation by a variety of Ca2+-mobilizing hormones, such as alpha 1 adrenergic agents, vasopressin and angiotensin II, causes a rapid phosphodiesterase-mediated hydrolysis of phosphatidylinositol-4,5-bisphosphate in the plasma membrane with the production of the water soluble compound myo inositol-1,4,5-trisphosphate (IP3) and the lipophilic molecule 1,2-diacylglycerol (DG). This review summarizes the recent evidence obtained in the liver that defines the roles of these products as intracellular messengers of hormone action. Intracellular Ca2+ mobilization is mediated by IP3, which releases Ca2+ from a subpopulation of the endoplasmic reticulum, resulting in a rapid increase of the cytosolic free Ca2+ concentration ( [Ca2+]i). Further effects of receptor occupancy are inhibition of the plasma membrane Ca2+-ATPase, despite net Ca2+ efflux, and an increased permeability of the plasma membrane to extracellular Ca2+. The activation of the phospholipid-dependent protein kinase C by DG does not alter Ca2+ fluxes across the plasma membrane. In contrast to some secretory cells, a synergism between protein kinase C activation and increased [Ca2+]i is not observed in liver. Activation of protein kinase C profoundly inhibits the response to alpha 1-adrenergic agonists, with only minimal effects on the vasopressin response. It is concluded that in liver the two inositol-lipid messenger systems, IP3 and DG, exert their effects by essentially separate pathways. PMID- 2579568 TI - Potassium movements in denervated frog sartorius muscle. AB - The movement of 42K+ across the sarcolemma and the resting membrane potential (VM) of normal and denervated frog sartorius muscle were studied under several experimental conditions in preparations initially equilibrated in 100 mM K+ and 219 mM Cl-. The results can be summarized as follows. In the absence of any driving force on K+, i.e., when the difference between VM and the K+ equilibrium potential (EK) is zero (VM - EK = 0), the K+ conductance (gK) was 368 microseconds . cm-2 in control and 282 microseconds. in denervated muscle. The reduced gK of denervated muscles results from the addition of the opposite changes in the conductances of a Rb+-sensitive inward rectifying pathway (gIR), which decreases, and a Rb+-insensitive linear channel (gL), which increases. Thus in control muscles gK (368 microseconds . cm-2) equals gIR (359 microseconds . cm 2) plus gL (9 microseconds . cm-2), while in denervated muscles gK (282 microseconds . cm-2) equals gIR (198 microsecond . cm-2) plus gL (84 microseconds . cm-2). Denervation significantly reduces the inward rectifying properties of the resting K+ permeability system. In the presence of outward driving forces on K+ (VM - EK greater than 0) of 35-50 mV, the Rb+-sensitive inward rectifier channel appears to close completely in both control and denervated muscles. In the latter, however, the effect was not as well maintained as in the former, suggesting that its closing mechanism might be altered by denervation. No changes were observed during the first 2 wk after denervation. PMID- 2579569 TI - Influence of pH change on redox state and CCK-induced secretion in isolated perfused rat pancreas. AB - The isolated perfused rat pancreas was used to examine the influence of the acid base status of the perfusing solution on the redox states of cytochromes and secretory responses. Lowering the pH in a perfusing solution (pHe) from 7.3 to 6.8 induced simultaneous oxidation of cytochromes aa3, b, and c + c1, and further lowering to 6.0 induced larger oxidation of the cytochromes. Raising the pHe from 7.3 to 8.0 induced reduction of the cytochromes. Continuous stimulation with synthetic C-terminal octapeptide of cholecystokinin (CCK-8) at 100 pM induced the maximum secretory responses (pancreatic juice flow, protein output, and amylase output) during perfusion with the standard solution. The responses were not inhibited at pHe 6.8 but were inhibited significantly at pHe 6.0 or 8.0. The responses induced by stimulation with 20 pM CCK-8 were completely inhibited when pHe was lowered to 6.0 and CaCl2 was removed from the perfusing solution. PMID- 2579570 TI - Hydrogen transport in papillary collecting duct of rabbit kidney. AB - To examine the cellular mechanisms of H+ transfer in rabbit papillary collecting duct (PCD), the 5,5-[14C]dimethyloxazolidine-2,4-dione-derived cell pH (pHi), the [3H]triphenylmethylphosphonium-derived membrane potential (Em), the lumen-to-cell Na+ concentration gradient [( Na+]o/[Na+]i), and cell potassium and chloride concentrations were studied at 37 degrees C in separated PCD from rabbits pretreated with deoxycorticosterone acetate. The variations in cell pH values were used as an index of changes in H+ secretion. Under standard conditions pHi was 7.30 +/- 0.04, [Na+]o/[Na+]i was 2.46 +/- 0.43, Em was 78 +/- 7 mV (cell negative), [K+]i was 105 +/- 10 mM, and [Cl-]i was 33 +/- 6 mM; the value of pHi thus remained higher than expected if H+ ions were passively distributed (6.13). Acetazolamide, 10(-4) M, alkalinized the cells. When [Na+]o/[Na+]i was reduced (low-Na+ medium or 10(-3) M ouabain), the cells did not acidify, suggesting that net H+ secretion did not decrease; also, pHi was not linked to the variations in the transmembrane chloride concentration gradients. When the cells were depolarized (low-Na+ medium), they became more alkaline; when the cells were hyperpolarized (10(-4) M amiloride), they became more acid; minor change in Em (ouabain) was associated with no change in pHi. It is concluded that: 1) H+ is actively secreted into the lumen; 2) active H+ secretion may not be secondary, via electroneutral Na+:H+ countertransport or HCl cotransport, but probably occurs via a primary H+ pump; 3) variations in Em probably affect pHi by acting on both the active H+ transport system and passive movements of HCO-3 (or its equivalent). PMID- 2579571 TI - Role of Ca2+ in serum-stimulated Na+ influx in normal and transformed cells. AB - Previous studies in human foreskin fibroblasts suggested that the mechanism by which serum stimulates Na+ influx is via a Ca2+-calmodulin-mediated event. In the present experiments in normal WI-38 cells (human lung fibroblasts), both the intracellular Ca2+ antagonist 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8) and the potent calmodulin antagonist trifluoperazine (TFP) blocked serum stimulated Na+ influx [TMB-8 concentration causing half-maximal inhibition (Ki) = 15 microM and TFP Ki = 10 microM]. Similar results were obtained in Swiss 3T3 cells. In contrast, in transformed WI-38 or Swiss 3T3 cells neither TMB-8 nor TFP had any effect on serum-stimulated Na+ influx (TMB-8 Ki greater than 100 microM and TFP Ki greater than 100 microM). In addition, when 45Ca2+ efflux measurements were made on normal and transformed cells, serum stimulated significant 45Ca2+ efflux (P less than 0.05) from WI-38 and Swiss 3T3 cells, while having no effect on 45Ca2+ efflux from simian virus 40 (SV40)-WI-38 or SV40-Swiss 3T3 cells. However, an elevation of intracellular Ca2+ can stimulate Na+ influx, since it was found that A23187 mimicked the effects of serum in both normal and transformed cells. These results suggest that the Ca2+-calmodulin-mediated event, which is thought to be involved in serum-stimulated Na+ influx in normal cells, may be bypassed or overridden in transformed cells. PMID- 2579572 TI - Effect of insulin on intracellular pH in frog skeletal muscle fibers. AB - The effect of insulin on intracellular pH (pHi) and membrane potential was studied in frog semitendinosus muscle fibers, using recessed-tip pH-sensitive glass microelectrodes and conventional 3 M KCl-filled microelectrodes. After a lag period of approximately 20 min, insulin [1 mU/ml, 0.1% bovine serum albumin (BSA)] produced a slow hyperpolarization of 2-5 mV and an alkalinization of 0.05 0.10 pH unit, which were both completed within 1 h and were not reversed by washing in insulin-free solution for 1 h. The effect of insulin on the pHi recovery rate from CO2-induced acidification was examined at various membrane voltages. At normal membrane voltage, insulin (400 mU/ml, no BSA) slightly increased the slow pHi recovery (from 0.01 to 0.04 delta pH/h). In fibers depolarized in 15 mM K to about -50 mV, insulin nearly tripled the recovery rate (from 0.05 to 0.13 delta pH/h). This insulin-induced recovery was abolished by 1 mM amiloride, a Na-H exchange inhibitor. The increased pHi recovery in 15 mM K thus represents an increased Na-H exchange, which may be due to an interaction between insulin and either membrane depolarization, per se, or increased intracellular Ca. In fibers depolarized in 50 mM K to about -25 mV, insulin did not affect recovery (0.28 delta pH/h). This lack of insulin effect might be due to fiber swelling or to the difference in the time course of elevation of intracellular Ca at -25 and -50 mV. These results are consistent with an alkalinizing effect of insulin in frog muscle mediated by Na-H exchange. PMID- 2579573 TI - Ion movements in membrane vesicles: a new fluorescence method and application to smooth muscle. AB - A method is described for studying ion permeabilities of membrane vesicles based on the principle that when membrane permeability to H+ is very high, the H+ movement is determined by the membrane potential generated by the H+ movement. The rate of H+ movement under these conditions thus gives a measure of the rate of dissipation of this membrane potential by comovement of anions or countermovement of cations present. Thus, by studying the H+ efflux using an impermeant cation and different anions, the membrane permeability to the anions can be assessed. Similarly, the use of an impermeant anion allows the study of the permeation of various cations. H+ movement was followed across the membranes by monitoring a change in the fluorescence intensity of the pH-sensitive dye pyranine trapped inside the membranes. This method when tested using phosphatidylcholine liposomes yielded the expected results, i.e., permeability of the liposomal membrane was: Cl- greater than SO2-4 and K+ greater than Na+. A plasma membrane-enriched fraction loaded with pyranine was isolated from estrogen dominant rat myometrium. The anion permeability characteristics of this membrane were studied using tetramethylammonium (TMA+) as the poorly permeant cation, and the cation permeability was studied using L-glutamate- as the poorly permeant anion. The anion permeabilities were D-glutamate- less than L-glutamate- less than glutarate2- less than Cl- less than or equal to SO2-4, and the cation permeabilities were TMA+ less than K+ less than Na+. It is hypothesized that the observed anomalously higher Na+ and SO2-4 movements may involve special mechanisms. PMID- 2579574 TI - Phorbol ester-induced changes of cytoplasmic pH in neutrophils: role of exocytosis in Na+-H+ exchange. AB - Cytoplasmic pH homeostasis was studied in intact and granule-free porcine neutrophils following activation with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). In intact cells, TPA activated at least two separate processes: a Na+ independent and amiloride-insensitive acidification, and a compensatory acid extrusion. The latter is Na+ dependent and blocked by amiloride and is likely to represent Na+-H+ exchange. Enucleated and degranulated neutrophils (cytoplasts) were prepared by sedimentation of cytochalasin B-treated neutrophils through a discontinuous density gradient. Cytoplasts responded to an artificially imposed acid load with activation of an amiloride-sensitive Na+-H+ exchange. TPA also activated both acid production and Na+-dependent acid extrusion in cytoplasts. The magnitude of the responses was comparable in intact neutrophils and in cytoplasts. These data suggest that 1) the nucleus and the secretory granules are not involved in the acidifying response to TPA, and 2) exocytosis of secretory vesicles is not required for activation of Na+-H+ exchange during acid loading or following treatment with the phorbol ester TPA. PMID- 2579575 TI - Control of secretion vesicle margination and lysis by glucose, IBMX, and glyburide. AB - We have attempted to define the effect of glucose, glyburide, and isobutylmethylxanthine (IBMX) upon secretion vesicle margination to the plasma membrane and granule lysis. Margination of secretion vesicles during exocytosis was assessed by measuring the recruitment of somatostatin (SRIF) receptors. Secretion vesicle lysis was studied by measuring insulin release into the incubation media. Our observations suggest that glucose directly affects both secretion vesicle margination and lysis. Both events are rapidly influenced by this secretagogue (within 10 min of incubation). Trifluoperazine (TFP) and removal of Ca2+ from the incubation media significantly reduced glucose-induced margination of secretion vesicles and their lysis (P less than 0.001). IBMX primarily influences the lysis of secretion vesicles and not their margination. IBMX caused a rapid increase in insulin secretion within 10 min without recruitment of SRIF receptors. Neither TFP nor the absence of extracellular Ca2+ affected IBMX-induced insulin release. Late enhancement in margination of secretion vesicles (30 min of incubation with IBMX) is probably related to the initial event of secretion vesicle lysis and is independent of extracellular calcium. Glyburide exerts its action in a manner similar to glucose, affecting both the lysis of secretion vesicles and their margination. However, the action of glyburide is independent of extracellular calcium and partially dependent upon calmodulin. PMID- 2579576 TI - Compensatory cell proliferation and growth in the rat heart after postnatal hypothyroidism. AB - Measurement of total DNA, RNA, and protein as well as weight of the heart in male rats at 10, 25, 50, and 90 postnatal days revealed that hypothyroidism, as induced by administration from birth of the goitrogen propylthiouracil (PTU), results in highly significant reductions in cardiac cell proliferation and cell growth. These inhibitory effects on hyperplastic and hypertrophic growths were less drastic during the suckling period than during the postweaning period. In the latter period, heart growth of the hypothyroid animals was found to remain at a standstill with regard to all the parameters measured. When, after 25 days of hypothyroidism, PTU treatment was discontinued, the retarded heart showed marked signs of rehabilitation and compensatory development. Indeed, by day 90, total DNA content had essentially compensated for its deficit but total RNA, protein content, and weight, though showing marked compensatory surges (from 80-90% deficit to 20-30%), were not yet fully compensated. The results clearly indicate that the growing heart has a marked ability to be rehabilitated from severe hypothyroid retardation, showing within 2 mo full compensation of cell number and nearly complete compensation of cell growth. It is suggested that rehabilitation of the heart is brought about by physiological restoration not only of the thyroid hormones but also of growth hormone and possibly other thyroid-dependent growth factors. PMID- 2579578 TI - Effect of hypoxia on feline intestinal capillary permeability. AB - The multiple-indicator dilution technique was used to investigate the permeability characteristics of capillaries in the cat small intestine during hypoxia. Reducing the arterial oxygen tension from 108 to 35 mmHg for 10 min increased the calculated equivalent pore radius of intestinal capillaries from 59 to 67 A. This effect was sustained for at least 15 min after the hypoxic episode. Hypoxia did not alter intestinal lymphatic protein clearance. Thus, the dimensions of the large pores did not change. This study demonstrates that 10 min of severe hypoxia increases vascular permeability in the small intestine and that this change occurs only in the small pores and is sustained, at least briefly, after restoration of normoxia. Hypoxia does not significantly change the permeability to macromolecules. PMID- 2579577 TI - Intestinal nerves and ion transport: stimuli, reflexes, and responses. AB - The effects of extrinsic and intrinsic nerves on ion and water transport by the intestine are considered and discussed in terms of their possible physiological function. Adrenergic nerves enter the small intestine via mesenteric nerves. Adrenergic tone is usually absent in tissues in vitro but is present in vivo. The nerves increase absorption in response to homeostatic changes associated with acute depletion of extracellular fluid. Cholinergic tone that reduces fluid absorption or causes secretion has been detected in the small intestine of humans, dogs, and cats and in the colon of humans. Extrinsic cholinergic fibers generally do not affect ion transport in small intestine but probably do so in colon. Whether peptides liberated in the mucosa affect enterocytes directly is not clear. Studies on humans and rabbits suggest that the role of substance P is minor. The physiological roles of vasoactive intestinal polypeptide (VIP) and somatostatin remain to be defined. Intraluminal factors also affect ion and water transport. Mucosal rubbing, distension, and cholera toxin cause fluid secretion; acid solutions in the duodenum cause alkaline secretion; these stimuli and hypertonic glucose liberate serotonin into the lumen, the mesenteric venous blood, or both. It has been proposed that the enterochromaffin cell is an epithelial sensory cell that responds to noxious stimuli within the lumen by liberating serotonin. The serotonin initiates a neural reflex through a nicotinic ganglion to liberate a secretagogue that acts on the enterocyte. The function of VIP in this proposed reflex is unclear. The variety of intraluminal stimuli that influence epithelial function implies that there is more than one type of epithelial sensory cell (or sensory mechanism). Prostaglandins may mediate the alkaline secretion caused by acid in the duodenum. There may be other effective substances. Although it has been known for years that intraluminal stimuli affect the coordination of smooth muscle functions, it is not known whether similar stimuli also influence salt and water transport as a meal traverses the alimentary canal. PMID- 2579579 TI - Failure of 16,16-dimethyl PGE2 to prevent inhibitory effect of ethanol on sodium transport in canine gastric mucosa. AB - By use of an in vitro canine gastric mucosal preparation, we evaluated the effects of ethanol (2, 4, 6, and 8%, vol/vol) and indomethacin (2.2 X 10(-4)M), with and without 16,16-dimethyl PGE2 pretreatment, on net sodium transport (JNanet) (mucosal to serosal) across gastric epithelium. Although administration of 2 or 4% ethanol to the mucosal bathing solution had no appreciable inhibitory effects on sodium transport, 6 and 8% ethanol and indomethacin significantly inhibited JNanet when compared with untreated control mucosa. This effect was accompanied by inhibition of transmucosal potential difference (PD) and short circuit current (Isc). In other mucosae exposed to dimethyl PGE2 (8 X 10(-6) M) in the serosal bathing solution, significant increases in JNanet, PD, and Isc were noted when compared with control mucosa. Addition of 6 or 8% ethanol to the mucosal solution of dimethyl PGE2-pretreated tissue resulted in significant decreases in PD, Isc, and JNanet below control values that were not significantly different from mucosa exposed to 6 and 8% ethanol without PG pretreatment. When indomethacin was added to the mucosal solution following dimethyl PGE2 pretreatment, only slight decreases in PD and Isc below control levels were observed, and the inhibitory effects on JNanet induced by indomethacin without such treatment were abolished. These findings suggest that stimulation of JNanet by prostaglandin may play a role in its ability to prevent indomethacin damage to gastric epithelium but does not appear to be of importance in mediating protection against ethanol damage. PMID- 2579580 TI - Tricyclic antidepressants and acid secretory response of rabbit gastric cells. AB - Tricyclic antidepressants have been tested for their effect on the H2-receptor mediated changes in cAMP, O2 consumption, and acid secretion in mucosal cells isolated from rabbit stomach. Amitriptyline (AMT) inhibited the action of histamine on both cAMP generation and O2 consumption in an apparent competitive fashion without altering these parameters in unstimulated cells. The onset of this inhibition was rapid and the time at which the increases in these functions had reached steady state was not changed. The Schild regression line for AMT was close to unity, and its Ki values for cAMP production or O2 consumption were 0.75 microM AMT. Imipramine and nortriptyline also caused a rightward shift in the dose-response curve of histamine-induced cAMP generation. The inhibitory action of AMT was specific to histamine in that AMT neither altered the effect of isobutylmethylxanthine on cAMP and respiration nor inhibited the increase in respiration caused by carbachol. However, at relatively high concentrations (250 500 microM), AMT inhibited the increase in cAMP caused by 5 and 100 microM prostaglandin E1 and inhibited the increase in respiration caused by both dibutyryl cAMP (DBcAMP) and by the combination of DBcAMP plus carbachol. Antidepressant drugs were also very potent inhibitors of acid formation as measured by [14C]aminopyrine accumulation (Ki, 1 microM). They inhibited acid formation in control cells, in cells stimulated by histamine, carbachol, and DBcAMP, and also the potentiated response to carbachol plus histamine or DBcAMP. The onset of this inhibition was also rapid, and adding 5 microM AMT to the cell suspension either together with histamine or after stimulation by histamine caused a rapid decline in aminopyrine accumulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579581 TI - Effect of pentagastrin on gastric mucosal histamine in dogs. AB - We studied the effect of pentagastrin on histamine content of gastric mucosa obtained from dogs with gastric fistulas to determine whether pentagastrin mobilizes cellular stores of histamine. Experiments were also performed on canine gastric mucosa in vitro to investigate the effects of pentagastrin on histamine release, per se. During in vivo studies basal histamine content averaged 0.9 nmol/mg wet wt tissue or 18.8 nmol/mg tissue prot. No significant difference in gastric mucosal histamine content occurred during intravenous administration of pentagastrin (6 or 16 micrograms . kg-1 . h-1) or saline (control), even though acid output from the gastric fistula increased significantly above control during pentagastrin infusion. Moreover, pentagastrin (10(-5) and 10(-8)M) did not release more histamine from gastric mucosa in vitro than the buffer (control), whereas Triton X-100 and the phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, alone and in combination with calcium ionophore A23187, released significant amounts of histamine above control values. From these experiments we conclude that pentagastrin did not alter histamine content of canine gastric mucosa in vivo, even though acid secretion was stimulated maximally, nor did pentagastrin release histamine in vitro. PMID- 2579582 TI - Protective effect of thyroxine but not parathyroidectomy on gentamicin nephrotoxicity. AB - Gentamicin nephrotoxicity increases renal cortex calcium and sodium and decreases renal cortex Na-K-ATPase activity. Human acute renal failure is accompanied by an increase in parathyroid hormone (PTH), a hormone that stimulates calcium uptake by tissues, and by a decrease in thyroid hormone, a hormone that increases renal cortex Na-K-ATPase activity. This study evaluated the role of extracellular calcium, PTH, and thyroxine in the pathogenesis of gentamicin nephrotoxicity. Chronically parathyroidectomized hypocalcemic rats (PTXG) given gentamicin (30 mg/kg s.c. twice daily for 8 days) were not protected from renal failure when compared with intact rats given gentamicin (NG), serum creatinine being 4.4 +/- 1.0 and 3.7 +/- 0.7 mg/dl, respectively, compared with normals (N), 1.2 +/- 0.1 mg/dl. Rats given thyroxine (10 micrograms/100 g body wt for 10 days) before and during gentamicin (PTXT4G) had a serum creatinine not significantly different from normals, 2.1 +/- 0.4 mg/dl. Plasma T4 was reduced in PTXG, NG, and PTXT4G compared with N, but the value for PTXT4G was significantly higher than for either PTXG or NG. Renal cortex Na-K-ATPase activity (mumol Pi X mg prot-1 X h-1) was lower in PTXG (2.3 +/- 0.2) and NG (2.4 +/- 0.5) compared with N (3.7 +/- 0.1), but activity was not reduced in PTXT4G (3.2 +/- 0.2) Thyroxine was protective also against gentamicin nephrotoxicity in intact rats. Clearance and excretion studies indicated that this protection did not result from an increase in glomerular filtration rate, filtered load of calcium, or urinary calcium excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579583 TI - Functional differentiation of cell types of cortical collecting duct. AB - Interference-contrast and fluorescent microscopy were used to differentiate between the two cell types--principal cells (PC) and intercalated cells (IC)--of the isolated perfused cortical collecting duct of the rabbit. Using Hoffman Modulation Contrast optics, two types of cell outlines could be identified: "hexagonal" and "circular" profiles. To characterize the cell types further, the binding of fluorescein-labeled peanut lectin, which has been shown to be specific for the luminal cell membrane of the IC, was monitored with epifluorescent techniques. The lectin was observed to bind to the circular cell type only, confirming it as the IC. With use of the fluorescent nuclear probe acridine orange to quantitate the total number of cells per millimeter of tubule length, the fraction of ICs (lectin-binding cells) was estimated to average 29%, and the fraction of PCs (non-lectin-binding cells) to average 71% of all cells. The studies were extended to functionally separate between the two cell types by monitoring cell swelling when a lumen-to-bath current pulse was passed. Current induced swelling was observed only in the PC and could be inhibited by the luminal addition of both the Na+ channel blocker amiloride, and the K+ channel blocker barium, thereby implicating the PC in the process of Na+ absorption and K+ secretion in this tissue. It is concluded that optical techniques can be applied to the cortical collecting duct perfused in vitro to differentiate between and study functional properties of the cell types. PMID- 2579585 TI - Adenosine as putative regulator of hepatic arterial flow (the buffer response). AB - In anesthetized cats, reduction of portal flow by occlusion of the superior mesenteric artery results in rapid increase in hepatic arterial (HA) flow that compensates for (buffers) 25.5 +/- 2.7% of the decreased portal flow. The hypothesis tested is that adenosine concentration produced near the HA resistance vessels is regulated by washout into portal vessels in intimate contact with the HA. Reduced portal flow leads to accumulation of adenosine and HA dilation. Several criteria for this hypothesis are met. First, adenosine is a potent dilator of the HA. Second, portal blood has access to HA resistance vessels as shown by a marked dilator effect of adenosine infused into the portal vein; it is therefore possible for adenosine produced locally to diffuse into portal blood. Third, dipyridamole potentiated the dilator response to adenosine as well as potentiating the buffer response from a 23% compensation for reduced portal flow to 34%. Fourth, 1-methyl-3-isobutylxanthine (MIX) antagonized exogenous adenosine and reduced the buffer response from 19% down to 5%. These data strongly support the hypothesis that the hepatic arterial buffer response is mediated by local concentrations of adenosine that are controlled by the rate of washout into portal blood. PMID- 2579584 TI - Interactions of vasopressin, cAMP, and prostaglandins in toad urinary bladder. AB - Prostaglandin (PG) inhibits the hydroosmotic effect of vasopressin. We therefore reexamined the interaction of vasopressin (VP), cAMP, and prostaglandins in toad bladder epithelial cells. Vasopressin slightly, but reproducibly, stimulated PGE2 and thromboxane B2 (TXB2) synthesis in cells prepared by the use of collagenase. When cells were prepared in the presence of a readily reversible cyclooxygenase inhibitor, ibuprofen, subsequent PGE2 synthesis was enhanced sevenfold but that of TXB2 was not. Increasing cAMP by either phosphodiesterase inhibition or 8 bromo-cAMP significantly inhibited both basal and VP-stimulated PGE2 synthesis. This inhibition was overcome by addition of arachidonic acid. Future studies employing these agents will have to consider these effects. VP enhanced 32P labeling of phosphatidylinositol (PI) and phosphatidic acid. This effect was prevented by the phosphodiesterase inhibitor, which also decreased phosphatidylcholine labeling. The results indicate that the phosphodiesterase inhibitor for cAMP may decrease PG formation by interfering with phospholipase activation. Furthermore, VP, similar to its effect in the liver, also increases PI turnover in toad bladder. This may initiate PG synthesis and provide a link among VP, cAMP, and calcium. A double-reciprocal feedback is proposed, whereby VP stimulates PG synthesis in a cAMP-independent manner and also inhibits PG synthesis in a cAMP-dependent manner. PMID- 2579586 TI - Low sodium attenuation of the Ca2+ paradox in the newborn rabbit myocardium. AB - The effect of low sodium (Na 24 mM) perfusate during Ca2+ depletion on mechanical function, tissue high-energy phosphate, creatine kinase (CK) release, and tissue potassium was studied in the arterially perfused newborn and adult rabbit heart. During Ca2+ depletion, the time for DT and +dT/dtmax to decline to half-maximal value in newborn muscles perfused with low Na (46 +/- 3 S) was significantly (P less than 0.05) longer than the value obtained with normal Na (14 +/- 1 S). Similar values were obtained in the adult. During Ca2+ repletion, the increase in resting tension and CK release was attenuated in the low Na groups, and the values in the newborn were significantly less than in the adult. The recovery of +dT/dtmax and tissue high-energy phosphates in the low Na groups were significantly greater than in the normal Na groups, and the values in the newborn were significantly greater than in the adult. These data suggest that low Na during the Ca2+-free period delays both cellular Ca2+ depletion during the Ca2+ free period and Ca2+ influx during Ca2+ repletion. This effect in the newborn is greater than in the adult and might be explained by Na+-Ca2+ exchange. PMID- 2579587 TI - Ca influx and sarcoplasmic reticulum Ca release in cardiac muscle activation during postrest recovery. AB - The recovery of twitch tension (T) and Ca influx after 5-s to 10-min rest intervals was studied in rabbit, rat, and frog cardiac muscle. Extracellular double-barreled Ca-selective microelectrodes were used to assess transsarcolemmal Ca influx. In rabbit ventricle, T at the first postrest beat (B1) exceeded T at the second beat (B2). T and Ca influx then increase toward steady state in a parallel fashion. Since Ca influx is small at B1, this beat may be more dependent on Ca stored in the sarcoplasmic reticulum (SR), and subsequent beats may more closely reflect Ca influx. We have examined this hypothesis using agents that may preferentially inhibit either SR Ca release or Ca influx. SR inhibitors caffeine (5 mM) and ryanodine (100 nM) changed the pattern of T recovery so that B1 was now less than B2 and more closely paralleled the recovery of Ca influx. Caffeine and ryanodine decreased steady-state T to 89 +/- 9 and 78 +/- 3%, respectively. In contrast, B1 was found to be less susceptible to inhibition than B2 when exposed to La or Co (influx inhibitors). These results are consistent with a rabbit ventricle model in which the SR Ca release contributes greatly to B1, the SR contribution declines while the Ca influx component increases, and Ca influx at steady state can account for a large fraction of steady-state T. In adult rat ventricle, caffeine and ryanodine decrease steady-state T to 33 +/- 2 and 13 +/- 3%, respectively, changing the T recovery pattern from a monotonic decrease to a monotonic increase. These results are consistent with a model qualitatively the same as rabbit ventricle. However, the SR can account for most of steady-state T in the rat, and thus its decaying characteristic dominates the control postrest recovery. By inhibition of SR Ca release, the increasing component ascribed to Ca influx becomes apparent. Similar experiments were done to establish an order of relative dependence on SR Ca release: adult rat ventricle greater than rabbit atrium greater than rabbit ventricle greater than frog ventricle. PMID- 2579588 TI - Norepinephrine-induced phasic activity in tail arteries from genetically hypertensive rats. AB - The effects of norepinephrine on contractile force development were studied in tail artery strips from spontaneously hypertensive stroke-prone (SHRSP) and Kyoto Wistar normotensive rats (WKY). The strips were mounted in physiological salt solution between a fixed base and force transducers; isometric contractions were recorded. Norepinephrine-induced were characterized by fluctuations in contractile activity, whereas contractile responses in arteries from WKY remained constant with time. The magnitude and frequency of phasic responses in SHRSP arteries varied directly with increasing concentrations of norepinephrine (1.8 X 10(-9) to 1.8 X 10(-6) M). The phasic responses induced by norepinephrine in SHRSP arteries were reversed by the following experimental interventions: 1) 10( 4) M ouabain; 2) 20 degrees C; 3) potassium-free solution; 4) 1.0 mM BaCl2; 5) 20 mM KCl; 6) 30 mM tetraethylammonium chloride; 7) chloride-free solution; and 8) 10(-7) M D 600 (calcium channel blocker). It is proposed that the phasic contractile responses to norepinephrine in SHRSP are related to altered movements of calcium and potassium across the cell membrane. This study demonstrates a very distinct functional individuality in the arterial vascular smooth muscle cell membrane of SHRSP. PMID- 2579589 TI - Dibutyryl-cAMP increases basolateral sodium conductance of mosquito Malpighian tubules. AB - Dibutyryladenosine 3',5'-cyclic monophosphate (cAMP) stimulates fluid secretion in isolated Malpighian tubules of the mosquito Aedes aegypti. In the present study the effects of cAMP on the basolateral membrane were studied with conventional microelectrodes. Membrane conductances were evaluated from the changes of the basolateral membrane potential (Vbl) consequent to ion changes in the bath. Under control conditions, Vbl measured -65.2 +/- 1.5 mV [83 impalements, 67 tubules]. A fivefold decrease in the bath Na concentration hyperpolarized Vbl by 10.2 +/- 0.6 mV [7], whereas a 4.4-fold increase in the bath K concentration depolarized Vbl by 7.9 +/- 1.0 mV [9]. In the presence of cAMP (10(-4) M) Vbl depolarized to -24.8 +/- 2.7 mV [9]. Vbl now hyperpolarized by 22.7 +/- 1.5 mV [7] for the bath Na change and depolarized by only 3.8 +/- 1.1 mV [6] for the bath K change. Thus the dominant effect of cAMP is the increase of the basolateral membrane Na conductance. This increase is consistent with 1) the depolarization of Vbl and 2) the hyperpolarization of the transepithelial voltage, the decrease of the transepithelial resistance, and the increase of Na and fluid secretion observed previously. Spontaneous oscillations of Vbl were observed and could not be attributed to cyclical changes of the basolateral membrane Na conductance. PMID- 2579590 TI - Electrolyte transport by alkaline gland of little skate Raja erinacea. AB - Transepithelial flux studies and conventional intracellular microelectrode measurements were employed to examine the mechanisms of ion transport by the alkaline gland of the male skate, Raja erinacea. These studies reveal that the transepithelial potential is 6.9 +/- 0.6 mV, lumen reference, and that the transepithelial resistance is 140 omega . cm2. The short-circuit current across this epithelium is entirely accounted for by net secretion of Cl, whereas transepithelial active transport of Na does not appear to be present in this tissue. Cl secretion and/or short-circuit current are reduced by serosal furosemide and abolished when the bathing solution Na is replaced with choline or when ouabain is added to the serosal bathing solution. Intracellular microelectrode studies reveal that the apical membrane potential is -43 mV, cell interior negative to the mucosal bathing solution. The transepithelial resistance in these tissues was 103 +/- 12 omega . cm2 and the apparent fractional resistance, i.e., the ratio of the change in apical membrane potential to the change in transepithelial potential produced by passing current across the epithelium was 0.39 +/- 0.09. Ion substitution experiments demonstrated that the apical membrane is dominated by a large Cl conductance while the basolateral membrane contains a barium-sensitive potassium conductance. These results suggest that the mechanism of Cl secretion by the alkaline gland is similar to the mechanism described for a variety of Cl secretory epithelia. PMID- 2579591 TI - A 'gift of God'?: The public health controversy over leaded gasoline during the 1920s. PMID- 2579592 TI - Primary neuroendocrine (Merkel cell?) carcinoma of the skin. II. An immunocytochemical study of 21 cases. AB - Twenty-one examples of neuroendocrine carcinoma of the skin were examined by the unlabeled antibody enzyme method for several neural hormones and peptides, carcinoembryonic antigen, S-100 protein, neuron-specific enolase, and three intermediate filaments: neurofilament, glial fibrillary acidic protein, and cytokeratin. Vasoactive intestinal polypeptide from two sources reacted with the neoplastic cells of four (18%) and seven (32%) of the cases, and pancreatic polypeptide reacted with scattered cells of one case. Neuron-specific enolase reactivity occurred in 50% of the cases. Neurofilament (70, 150, 200 kilodaltons) was strongly positive in 40% of the tumors whereas neurofilament (200 kilodaltons) was negative. Two monoclonal anticytokeratin antibodies of 54 kilodaltons and 44-54 kilodaltons reacted in 77% and 64% of the cases, respectively, in a distribution similar to the neurofilament. Sections reacted with antisera against cytokeratins of higher molecular weight were negative. The demonstration of vasoactive intestinal polypeptide, pancreatic polypeptide, neurofilament, and neuron-specific enolase is evidence of the neuroendocrine nature of this neoplasm. PMID- 2579593 TI - Malignant mesothelioma and CEA staining. PMID- 2579594 TI - Primary neuroendocrine (Merkel cell?) carcinoma of the skin. I. A clinicopathologic and ultrastructural study of 43 cases. AB - The clinical and pathologic features of 43 cases of primary neuroendocrine carcinoma of the skin are reported. These tumors arise in the dermis and subcutaneous tissues of elderly individuals. The head and neck are the most common primary sites followed by the lower and upper extremities and trunk. Characteristic histologic features include round cells with scanty amphophilic cytoplasm and vesicular nuclei with multiple small nucleoli. The cells are arranged in sheets, solid nests, or anastomosing trabeculae. Collections of perinuclear intermediate filaments, cytoplasmic dense-core membrane-bound secretory granules, complex intercellular junctions, and cytoplasmic spinous processes are the principal fine structural features. These ultrastructural findings are similar to those of the normal cutaneous Merkel cell. The natural history of this neoplasm is characterized by local recurrence in 30% of cases, regional lymph node metastases in 65% of cases, and distant metastases in 40%. One-third of the patients were dead because of their tumors. Treatment of extensive local or distant metastatic disease with chemotherapy or radiotherapy resulted in only short-term palliative response. PMID- 2579595 TI - Arthritis and inflammatory bowel disease. PMID- 2579596 TI - Filaggrin, the matrix protein of keratin. PMID- 2579597 TI - Equivalent inhibition by terbutaline of anti-human IgE skin responses in atopic and non-atopic subjects. AB - Previous studies have shown that pretreatment of skin with beta 2-adrenoceptor stimulants antagonizes anti-human IgE elicited wheal and flare reactions in atopic and non-atopic subjects. This experimental system was employed to further study the hypothesis that atopic disease and bronchial asthma unrelated to atopy might be associated with a beta-adrenoceptor defect. Eight patients with extrinsic and 10 patients with intrinsic asthma deprived of oral bronchodilator treatment and corticosteroids for at least a week, and in a clinically stable condition, 10 patients with extrinsic rhinitis and on no treatment, as well as age and sex matched healthy control subjects showed almost identical dose response relations for the inhibitory effect of intradermally injected terbutaline (0.25-100 ng), on anti-IgE elicited skin reactions. In four asthmatic patients the inhibitory effect of terbutaline did not change following a treatment period with oral terbutaline and theophylline. The data do not support the presence of a cutaneous mast cell beta 2-adrenoceptor defect in patients with atopy or bronchial asthma unrelated to atopy. PMID- 2579598 TI - Inhibition of the late phase response to anti-IgE in humans by indomethacin. AB - The hypothesis of cyclooxygenase derivates of arachidonic acid as putative mediators of late phase skin reactions (LPR) was evaluated by studying the effect of indomethacin and naproxen on anti-IgE elicited skin reactions in healthy volunteers. Indomethacin 50 mg t.i.d., 48 h prior to and up to 24 h following challenge with anti-IgE 1/3300 (v/v), produced a slight attenuation of the flare response and a 35% inhibition of the LPR (P less than 0.05) at 1-24 h as compared with placebo (n = 11). Naproxen, 250 mg, b.i.d. showed analogous anti-LPR effect (n = 4, P less than 0.05). Intradermally (i.d.) injected indomethacin, 75 micrograms (7 X 10(-3) mol/l), attenuated the flare and LPR to anti-IgE 1/330 at 1-6 h (n = 12, P less than 0.01). Indomethacin, oral and i.d., enhanced the LPR to various dilutions of anti-IgE in 30% of the individuals. The results suggest that prostaglandins and thromboxanes participate in the development of an LPR in human skin. PMID- 2579599 TI - Mediators of hypersensitivity and "fog"-induced asthma. AB - Seven asthmatic and five normal subjects inhaled increasing amounts of nebulized water ("fog"). Neutrophil chemotactic activity (NCA), histamine and FEV1 measurements were undertaken before and at time intervals after challenge. In asthmatics, the mean maximal reduction in FEV1 (+/- 1 SD) was 46.6% +/- 11.5; whereas, in normal subjects, the reductions were less than 20% of pre-challenge values after the inhalation of 33 ml of water. There were no significant differences in the pre-challenge values for NCA between the asthmatics and the normal controls. When the highest values for NCA during the 30 min after challenge in the asthmatics were compared with controls there was a significant increase (P less than 0.02). The percentage change in NCA was also significantly greater in the asthmatics compared with the controls at 10 min after challenge (P less than 0.05). Fog-induced NCA was shown to be associated with proteins with approximate molecular weight of 600,000 daltons (as assessed by gel filtration chromatography on Sephacryl-S400). There was an increase in plasma histamine in the asthmatics after challenge but this was not significantly greater than the controls. These findings support the view that mediators might be involved in fog induced asthma, possibly as a result of mast cell degranulation by "osmotic shock". PMID- 2579600 TI - Bronchial and basophil reaction to polymyxin B in asthmatic patients. AB - The hypothesis that increased reactivity to polymyxin B in asthmatic patients is not limited to the bronchi but also exists in basophils was investigated in 26 atopic asthmatic subjects. Quantification of basophil degranulation induced by polymyxin B was performed using a flow-cytometric method. Significant degranulation was noted in 17 patients, but in none of 10 healthy controls. There was close relationship between basophil "releasability" to polymyxin B and bronchial reactivity to inhaled polymyxin B. These findings support the hypothesis. PMID- 2579602 TI - Cardiac dysrhythmias associated with chemical peeling with phenol. PMID- 2579601 TI - Transport of horseradish peroxidase across monkey trophoblastic epithelium in coated and uncoated vesicles. AB - This study used membranous chorion of the macaque monkey placenta to examine uptake and processing of exogenous proteins. Tissue was incubated with either cationic or anionic horseradish peroxidase. Incubation time was varied between 5 25 min to follow the endocytic pathways. In spite of some differences in binding, uptake and processing of the isozymes was similar. In the presence of tracers at 37 degrees C both horseradish peroxidases were taken up in large (150-175) nm diameter) coated vesicles. In addition, coated tubules 300-400 nm in length and 50-100 nm in diameter were seen in the apical cytoplasm. Studies using ruthenium red indicated that the coated tubules were derived from long coated invaginations of the free surface that pinch off into the apical cytoplasm. Often, the tubules bud off small (85-105 nm diameter) protein-filled coated vesicles which traversed the cytoplasm and fused with the basal-lateral plasma membrane. In other cases, the tubules or vesicles lost their clathrin coats and fused to form larger endocytic vesicles which later fused with phagolysosomes. After long incubation, larger uncoated vesicles (endosomes) were seen releasing their contents at the basal-lateral membrane. These results suggest that multiple transport pathways exist in this epithelium. The first, involving only coated structures, may function to sort and concentrate specific ligands important for embryonic development. The second, involving the formation and translocation of large uncoated vesicles to the basal-lateral membrane, may also provide nutrients to the embryo. A third pathway directs the protein to phagolysosomes where it is presumably degraded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579603 TI - A comprehensive allergen extract monograph with advice for the patient. AB - Interest in increased patient education regarding medications they receive is gathering momentum. An historical overview is provided as well as summaries of available patient information resources. To date little such information has been available for patients receiving immunotherapy with allergen extracts. A comprehensive draft monograph driven from multiple sources for the various products available is proposed, as well as suggested advice for patients. Comments and suggestions for revision are solicited, prior to proposed inclusion in a national patient information publication. PMID- 2579604 TI - Anaphylactic hypersensitivity to mercurochrome (merbrominum). AB - By the use of intradermal tests, passive transfer (P.K.), and an in vitro histamine release test, we were able to demonstrate immediate hypersensitivity to Mercurochrome in a young man who had suffered anaphylactic shock after having contact with this antiseptic. Cross-reactions among different organic mercurial compounds were observed. PMID- 2579605 TI - Value of measurements of allergen-specific IgG antibodies as an in vitro monitor of specific immunotherapy. PMID- 2579606 TI - Photofield mapping in the evaluation and management of subretinal neovascularization. AB - Photofield mapping is a useful method for classifying subretinal neovascularization based on its area and location. Careful central field mapping is performed to delineate scotomata during evaluation of patients with subretinal new vessels. A photofield map is then constructed by projecting 35 mm fundus photographs and angiograms onto an appropriately-oriented central visual field map. The composite map (photofield) documents the location and relationship of scotomata, subretinal neovascularization, foveal avascular zone, and retinal blood vessels. The areas of subretinal neovascularization and scotomata are measured in square millimeters with a planimeter. The distance between their closest edge and the center of the foveal avascular zone is measured in millimeters. This method permits quantitative comparison of results with different photocoagulation protocols and instrumentation. Such comparative analysis may help improve the technique and instrumentation used in laser photocoagulation of subretinal neovascularization. PMID- 2579607 TI - Argon vs krypton laser lesions: is the wavelength more important than the power. AB - Conventionally, unnecessarily intense laser power is advocated for the treatment of subretinal neovascular membranes. Among the four variables determining the adequacy of the laser lesion, namely spot size, duration of exposure, wavelength, and power, the latter is seldom if ever directly considered. Patients with subretinal neovascular membranes may be satisfactorily treated using the unfiltered argon blue-green laser wavelengths and reduced power as an additional option to the filtered argon green and wavelength or krypton yellow or red wavelengths. PMID- 2579608 TI - Relief of the pain of unresectable carcinoma of pancreas by chemical splanchnicectomy during laparotomy. PMID- 2579609 TI - [Therapeutic indications for sotalol 160 mg]. PMID- 2579611 TI - On science, scaling, and support. PMID- 2579610 TI - Dimethylglycine and reduction of mortality in penicillin-induced seizures. PMID- 2579612 TI - Uptake and clearance rates for kepone in two marine fish species. PMID- 2579613 TI - Circulating hyaluronate in rheumatoid arthritis: relationship to inflammatory activity and the effect of corticosteroid therapy. AB - The mean serum hyaluronate concentration in a group of patients with rheumatoid arthritis (n = 37) was 232 +/- 182 (SD) microgram/l and significantly greater (p less than 0.001) than that of age and sex matched healthy controls (mean level 42 +/- 25 micrograms/l) as well as that of patients with ankylosing spondylitis (mean level 58 +/- 33 micrograms/l). In rheumatoid arthritis positive correlations were found between serum hyaluronate and acute-phase plasma proteins, while neither rheumatoid factor titre nor the presence of circulating immune complexes were related to the hyaluronate levels. Increased serum hyaluronate could not be explained by impaired renal or liver function or by drug therapy. During treatment with corticosteroids but not with non-steroidal anti inflammatory drugs the serum hyaluronate concentrations were significantly reduced. The data obtained suggested an increased production of hyaluronate in rheumatoid arthritis, and the increase seems to be related to the activity of the inflammatory process. PMID- 2579614 TI - Klebsiella 'modifying factor': binding studies with HLA-B27+ and B27- lymphocytes. AB - On the basis that extracts of some klebsiella organisms bind selectively to the lymphocytes of HLA-B27+ individuals and induce the appearance of new antigens, attempts were made to detect the binding of klebsiella products to HLA-B27+ and B27- lymphocytes by a number of different techniques. Firstly, blocking of the binding of two different HLA-B27 specific monoclonal antibodies to HLA-B27+ lymphocytes has been examined following exposure of the lymphocytes to a cell free culture filtrate from K. pneumoniae K21 and K43. There was no reduction in the cytotoxicity of either antibody, suggesting that neither of the epitopes detected by the anti-HLA-B27 monoclonal antibodies is a binding site for klebsiella products. Secondly, we have studied the binding of partially purified, radiolabelled klebsiella products to healthy HLA-B27+ and B27- lymphocytes. There was no significant difference either in terms of numerical counts bound or by comparing, by SDS-PAGE analysis, the molecules bound to each cell type. At the level of sensitivities of these techniques we can detect no difference in binding of klebsiella products to the lymphocytes of healthy HLA-B27+ and B27- individuals. PMID- 2579615 TI - Stimulants, urinary catecholamines, and indoleamines in hyperactivity. A comparison of methylphenidate and dextroamphetamine. AB - Children with attention deficit disorder with hyperactivity were given either methylphenidate hydrochloride or dextroamphetamine sulfate to compare the effects on urinary excretion of catecholamines, indoleamines, and phenylethylamine (PEA). Methylphenidate's effects were distinctly different from those of dextroamphetamine. After methylphenidate administration, both norepinephrine (NE) and normetanephrine (NMN) concentrations were significantly elevated, and there was a 22% increase in excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG). In contrast, after dextroamphetamine treatment, MHPG excretion was significantly reduced and NE and NMN values were unchanged. Excretion of dopamine and metabolites was unchanged by either drug. Urinary PEA excretion was not significantly changed after methylphenidate treatment, but increased 1,600% in response to dextroamphetamine. Methylphenidate treatment did not significantly alter serotonin or 5-hydroxyindoleacetic acid excretion. Effects of dextroamphetamine were not tested. PMID- 2579616 TI - Atrophy limited to the third ventricle in chronic schizophrenic patients. Report of a controlled series. AB - Computed tomographic scans of 30 chronic schizophrenic patients and 26 matched medical controls were blindly assessed for ventricular brain ratio, cortical atrophy, third-ventricle diameter, and cerebellar atrophy. Schizophrenic patients had significantly larger third ventricles than the medical controls. There was no difference in the other brain morphologic variables. Phenomenology, drug response, CSF levels of 5-hydroxyindoleacetic acid, 3-methoxy-4 hydroxyphenylglycol, homovanillic acid, and a wide variety of clinical variables did not correlate with any measure of brain morphology. Clinicopathologic correlates of brain morphology may be limited to those patients with significant atrophy. PMID- 2579617 TI - Monoclonal antibodies and "routine" paraffin sections. PMID- 2579618 TI - Cellular immunolocalization of S100 protein within fixed tissue sections by monoclonal antibodies. AB - Monoclonal antibodies (MoAb) that cross-react with the shared epitopes of S100 protein have been prepared from mouse hybridoma cell lines and partially characterized. Nine of these MoAb were applied to sections of formaldehyde-fixed paraffin-embedded human tissues that were stained by immunohistochemical techniques. Three of these MoAb give uniformly and reproducibly positive staining in appropriate cell types when stained by avidin-biotin methods. Three of the MoAb were judged to be negative, although some MoAb gave inappropriate staining patterns. The three remaining MoAb showed either great heterogeneity in their staining patterns or intensities, or gave a lesser degree of reproducibility in a given tissue or neoplasm. One of the MoAb designated 15E2E2 that belonged to the first group of reproducibly staining antibodies was used to stain a larger number of normal human tissues and neoplasms. The staining that was observed appeared to recapitulate that which was previously described for conventional S100 protein antibodies. Monoclonal antibodies may, therefore, have a role in selected cases where standard microscopy is equivocal for a specific tissue diagnosis, or where independent verification of the diagnosis would be beneficial. PMID- 2579619 TI - Identification of calcium oxalate crystals using alizarin red S stain. AB - Calcium oxalate crystals stain with alizarin red S at a pH of 7.0 but not at a pH of 4.2. In contrast, calcium phosphate and calcium carbonate stain at a pH of both 7.0 and 4.2. This difference allows presumptive identification of calcium oxalate deposits. The identity of calcium oxalate can then be confirmed by its insolubility in 2M acetic acid, since both calcium carbonate and calcium phosphate are soluble. We have applied this procedure for several years and have found it to be a rapid, reliable, and technically simple procedure for distinguishing calcium oxalate from other calcium deposits. PMID- 2579620 TI - Myoepithelial cells in salivary gland tumors. An immunohistochemical study. AB - Normal salivary glands and 55 salivary gland tumors were examined by immunostaining (immunoperoxidase [IMP] and immunofluorescence [IMF]) to identify myoepithelial cells (MCs) and speculate on their role in the histogenesis of the tumors. The classic (C) MCs of normal salivary glands stained by IMP with antibodies to cytokeratin and S100 protein and stained by IMF with the same antibodies and with antibodies to vimentin and actin. Modified (M) MCs of pleomorphic adenomas stained positively by IMP and IMF with all of the preceding antibodies. In many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas, variable numbers of CMCs and MMCs stained positively by IMP with anti-cytokeratin and anti-S100 protein antibodies. No MCs were detected in adenolymphomas or acinic cell carcinomas. We believe that MCs play a major role in the histogenesis of pleomorphic adenomas and may also be important in many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas. PMID- 2579621 TI - New stain for fungi and basement membrane. AB - The availability of a single stain for both glomerular basement membrane and fungi is described herein. The procedure is easily reproducible and the length of the entire procedure is relatively short. This method can also be applied to frozen-section material to detect the existence of pneumocystosis in the case of acquired immunodeficiency syndrome. PMID- 2579623 TI - [Mechanisms of neovasculogenesis and its regulation in the adult organism]. AB - Under regeneration of organs, wound healing, tumour growth, inflammatory processes, under many compensatory and adaptive reactions in the organism of mature persons and animals, an inevitable formation of new blood vessels (neovasculogenesis) takes place. Modern notions on mechanisms of neovasculogenesis are based on the fact that new formation of vessels in a mature organism includes processes of migration and replication of endothelial cells according to the principle: "endothelium from endothelium". The literature data on neovasculogenesis in the mature organism are summarized and compared with the authors' investigations. Characterization of new blood vessels growth is presented; ultrastructural organization of endotheliocytes in growing capillaries, formation of barrier-transport properties in the newly formed vessels, role of inductors and inhibitors of neovasculogenesis in creation of new vascular formations are considered. PMID- 2579624 TI - [Potentials for using an equipment unit for demonstrating slides of micropreparations with their synchronous description in a department of pathological anatomy]. PMID- 2579622 TI - Reprioritization of hepatic plasma protein release in trauma and sepsis. AB - We studied the temporal pattern of seven hepatic synthesized plasma proteins in 26 severely injured patients beginning in the immediate posttrauma period. Clinical sepsis developed in ten patients between three and eight days after injury, and 16 patients had nonseptic courses. In the initial five days after injury, except for albumin, all acute-phase protein levels rose. However, if sepsis developed, C-reactive protein, fibrinogen, ceruloplasmin, and alpha 1 antitrypsin levels continued to be elevated after the initial five posttrauma days, while transferrin, albumin, and alpha 2-macroglobulin levels fell. This differential response became more extreme as sepsis progressed. Covariance analysis of the regression of the five true acute-phase hepatic proteins on C reactive protein showed that, when sepsis occurred after major traumatic injury, the C-reactive protein rise was associated with a significant reprioritization of hepatic acute-phase plasma protein release. This reprioritization response seems to be both a predictor of sepsis as well as a measure of the adequacy of the host response to trauma and sepsis. PMID- 2579625 TI - Serotonin and 5-hydroxyindoleacetic acid in CSF. Difference in Parkinson's disease and dementia of the Alzheimer's type. AB - Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in the sixth, 13th, and 20th milliliters of CSF in patients with dementia of the Alzheimer's type (DAT) and Parkinson's disease (PD), and in an aliquot of CSF in controls. In patients with PD there was a positive correlation between 5-HT and 5 HIAA levels in the 20th milliliter of CSF, while in patients with DAT there was a negative correlation of these levels in this CSF fraction. In patients with the senile form of DAT the 5-HIAA levels in the 20th milliliter of CSF were higher than in patients with PD. These results indicate differential involvement of the serotoninergic system in DAT and PD, and may lead to the development of a chemical marker for DAT. PMID- 2579627 TI - Ocular neovascularization. Tissue culture studies. AB - The proliferative activity of a number of intraocular fluids, bovine retinal extract, and normal serum (from humans and cynomolgus monkeys) was investigated by in vitro tissue culture studies, with the use of tritiated thymidine incorporation by the cultured endothelial cells of human umbilical veins. There was increased tritiated thymidine incorporation by (1) the aqueous, vitreous, and intraocular fluid (IOF) (which filled the eye after lensectomy and vitrectomy) removed from cynomolgus monkey eyes with iris neovascularization or with neovascular glaucoma (NVG) that developed after experimental retinal vein occlusion, (2) by aqueous and vitreous removed from human eyes with NVG or proliferative diabetic retinopathy; (3) by the serum, and (4) by the bovine retinal extract. However, tritiated thymidine incorporation was not increased by the normal aqueous, vitreous, or IOF. PMID- 2579626 TI - CSF monamine metabolites in movement disorders and normal aging. AB - We measured four monoamine metabolite levels in CSF before and after probenecid administration to normal controls and to patients with Huntington's disease (HD), dystonia, and tardive dyskinesia. We identified differences only for the dopamine metabolite homovanillic acid (HVA), which showed increased baseline values and decreased turnover in normal aging, but decreased baseline values and normal turnover in HD. These results suggest that dopamine neurons are linked both to normal aging and to HD and that CSF HVA studies can distinguish differences in the functioning of dopamine neurons in normal aging and HD. PMID- 2579628 TI - Granulomas in sympathetic ophthalmia and sarcoidosis. Immunohistochemical study. AB - Monoclonal antibodies were used to identify cells that form choroidal granulomas and Dalen-Fuchs nodules in sympathetic ophthalmia as well as the granulomas of sarcoid. Immunohistochemical analysis of frozen sections of fresh human tissues obtained after enucleation (sympathetic ophthalmia) and lung biopsy (sarcoid) was performed by the avidin-biotin-peroxidase complex method. The majority of the inflammatory cells within these lesions were identical and were composed mainly of cells originating from bone marrow-derived monocytes (reticuloendothelial system) probably representing immunologically stimulated granulomas. This study suggests possible immune phenomena that may take part in the pathogenesis of sympathetic ophthalmia and provides some insights into the possible mechanism of formation of choroidal granulomas and Dalen-Fuchs nodules in this disease. PMID- 2579629 TI - Scanning electron microscopy of the ocular vasculature in retinopathy of prematurity. AB - Clinicoanatomopathologic correlations in a case of the retinopathy of prematurity are reported. A premature infant delivered at 28 weeks of gestation (weight, 900 g) was hospitalized for a number of health problems, including bronchopulmonary dysplasia and respiratory distress syndrome. Ophthalmic examination, at the age of 5 months, disclosed stage 1B retinopathy of prematurity. The patient died at the age of 161 days; both eyes were taken for scanning electron microscopy and histopathologic studies. Scanning electron microscopy findings included absence of retinal capillaries, anterior uveal neovascularization originating from the venous side, and a coincidental typical coloboma of the optic nerve and choriocapillaris. Histopathologic findings confirmed iris stromal neovascularization, showed retinal neovascularization with proliferation into the vitreous and avascular areas between the midperiphery and ora serrata. PMID- 2579630 TI - Drusen of the optic nerve associated with retinitis pigmentosa. AB - Globular excrescences of the optic nerve associated with retinitis pigmentosa have been interpreted as drusen or as astrocytic hamartomas. The histopathologic and ultrastructural findings of globular excrescences of the peripapillary region of the optic nerve associated with retinitis pigmentosa were described in a 22 year-old patient who died in a car accident. From our findings we conclude that the globular excrescences of the optic nerve associated with retinitis pigmentosa are definitely drusen and not astrocytic hamartomas. PMID- 2579632 TI - The histopathology of corneal neovascularization. Inhibitor effects. AB - With the use of a previously described model of corneal neovascularization induced by thermal cautery, we examined the effects of inhibitors on both the incidence of corneal neovascularization and the degree of inflammatory cell response. Three known inhibitors of corneal neovascularization, 1% prednisolone acetate, indomethacin, and 0.3% flurbiprofen, were studied and the results were compared with those in saline-treated controls. As expected, corneal neovascularization, preceded by conjunctival and corneal polymorphonuclear leukocyte (PMNL) infiltration, occurred in all control animals. Corneal neovascularization did not occur in any of the inhibitor-treated eyes. Histopathologically, both conjunctival and corneal PMNL counts in the treated eyes were markedly reduced compared with controls. These findings are consistent with the hypothesis that inflammatory cells, particularly PMNLs, are closely associated with the initiation of corneal neovascularization. PMID- 2579631 TI - An antimelanoma monoclonal antibody and the histopathology of uveal melanomas. AB - Monoclonal antibody ME491 identifies a cutaneous melanoma-associated antigen in formaldehyde-fixed, paraffin-embedded tissues. This antibody was applied to tissue sections from 79 cases of formaldehyde-fixed, paraffin-embedded uveal melanomas. Sixty-nine (87.3%) of the 79 cases showed staining by monoclonal antibody ME491, thus demonstrating an antigen shared by cutaneous and uveal melanomas. No relationship between the staining pattern and the patient outcome was detected. Twelve (85.7%) of the 14 cases in which balloon cells were present stained with the antibody. The antibody stained the long posterior ciliary nerve in 12 (38.7%) of 31 cases in which the nerve was present in tissue sections. The antibody cross reacted with the retinal pigment epithelium (16.5% of cases) and a variety of normal nonocular tissues. PMID- 2579633 TI - Role of lensectomy and posterior capsule in movement of tracers from vitreous to aqueous. AB - The rate of movement of 20,000- and 70,000-dalton dextran from vitreous to aqueous was determined after extracapsular lensectomy in rabbits with an intact posterior capsule. Dextran was injected into the vitreous, and 3.5 hours later the aqueous concentration of 20,000-dalton dextran was 10.3-fold greater in the aphakic than the phakic eye. The aqueous concentration of the 70,000-dalton dextran was 3.9-fold greater in the aphakic eye after 3.5 hours. Thus, extracapsular lensectomy with an intact posterior capsule increases the rate of movement of 20,000- and 70,000-dalton dextran from the vitreous to the anterior chamber. In addition, the movement of tracers from vitreous to aqueous is increased further when the posterior capsule is opened. PMID- 2579634 TI - Simulated treatment of recurrent choroidal neovascularization in primate retina. Comparative histopathologic findings. AB - We simulated the treatment of recurrent choroidal neovascular membranes (CNVM) by applying two courses of laser treatment to monkey retinas. Argon green, argon blue-green, and krypton red lasers (KRLs) were used in juxtafoveal, papillomacular bundle, and nonmacular areas. The effects were examined clinically and histopathologically. Results of once-treated control eyes were consistent with those of previous studies. Repeat treatment, however, resulted in full thickness retinal destruction or necrosis with all laser modalities and in all fundus locations. These results are consistent with the absorptive characteristics of xanthophyll and melanin and suggest only limited advantages to the KRL when treatment of recurrent CNVM is performed in a previously treated area of the fundus. However, treatment of recurrent CNVM is still probably most successful with a KRL, because recurrent CNVM is usually at a border of a photocoagulation scar, where the retina is still untreated, and because histologic studies have demonstrated inner retinal sparing with a KRL in juxtafoveal areas. PMID- 2579635 TI - Cytoskeletal proteins in oncocytic tumors of the parotid gland. AB - Oncocytomas and Warthin's tumors were studied ultrastructurally and with immunofluorescence microscopic techniques against cytokeratins, desmin, vimentin, and actin, the latter characterizing myoepithelial cells. The cell types were found within oncocytomas, one type packed with mitochondria and virtually without filaments, the other contained fewer mitochondria but large amounts of cytokeratins. In Warthin's tumors, all cells contained cytokeratins, the basal cell to a much higher degree. No tumor cells contained vimentin or desmin. Actin was found only close to the apical cell surface in the cylindrical cells in the Warthin's tumors and around the few acinar lumina found in the oncocytomas; thus, a myoepithelial origin of oncocytic tumors of salivary glands seems less plausible. The similarity in staining pattern, namely the pronounced dimorphism of both tumor types, indicates a common progenitor of oncocytomas and the epithelial component in adenolymphomas. PMID- 2579636 TI - Handicaps and health problems in 2 year old children of birth weight 500 to 1500 g. AB - Fifty-nine infants of birthweight 500 to 999 g born in 1977 to 1980 and 132 infants of birthweight 1000 to 1500 g born in 1977 to 1978 were reviewed at two years corrected age. For the whole cohort, cerebral palsy was found in 12.6%, bilateral deafness in 1%, blindness in 1% and severe developmental delay in 12%. There was no significant difference in these disabilities between the groups of larger and smaller infants; 37.7% of the cohort was readmitted to hospital on at least one occasion, 35.6% of children had wheezing episodes and/or lower respiratory tract infections which together accounted for 51% of hospitalizations. The infants of birthweight 500 to 999 g tended to require more frequent and prolonged hospitalizations. Dolicocephalic head shape, chest deformities, iatrogenic sequelae from intensive care, poor growth and cicatricial retrolental fibroplasia were significantly more frequent in children of birthweight 500 to 999 g. Parents reported that 39% of their children had 'colic', 31.6% had sleep disturbance and 25% had multiple behavioural problems. Low frustration tolerance, inability to wait, hypo- or hyperactivity and an inappropriate relationship with the mother as measured by the psychologist all occurred significantly more frequently in children of birthweight of less than 1000 g. This report confirms the belief that a comprehensive follow-up is required for very low birthweight (VLBW) children because significant health problems continue after primary hospitalization. PMID- 2579637 TI - Comparison of abilities of preterm and maturely born children at 5 years of age. AB - This study investigated whether the development of 5 year old preterm born children was appropriate for age and equivalent to or different from their peers who were full term at birth. At the adjusted age of 5 years, the development of 106 children born 5 or more weeks before term was compared with the development of 103 children who were born at term. This latter group of children were matched to the preterm group in sex, year of birth, birthplace, race and residential location. No cerebral palsy children were included in either subject group. The results indicated a significant difference between the two groups. Factors distinguishing the preterm children from their full term peers included small involuntary hand movements, less competent gross motor ability, poorer verbal performance and more variability in behaviour, postural response and balance. A higher than average incidence of minor motor, speech, behaviour and learning problems in early school years is probable. PMID- 2579638 TI - Zymogen-activation kinetics. Modulatory effects of trans-4 (aminomethyl)cyclohexane-1-carboxylic acid and poly-D-lysine on plasminogen activation. AB - The kinetics of plasminogen activation catalysed by urokinase and tissue-type plasminogen activator were investigated. Kinetic measurements are performed by means of a specific chromogenic peptide substrate for plasmin, D-valyl-L-leucyl-L lysine 4-nitroanilide. Two methods are proposed for the analysis of the resulting progress curve of nitroaniline formation in terms of zymogen-activation kinetics: a graphical transformation of the parabolic curve and transformation of the curve for nitroaniline production into a linear progress curve by the addition of a specific inhibitor of plasmin, bovine pancreatic trypsin inhibitor. The two methods give similar results, suggesting that the reaction between activator and plasminogen is a simple second-order reaction at least at plasminogen concentrations up to about 10 microM. The kinetics of both Glu1-plasminogen (residues 1-790) and Lys77-plasminogen (residues 77-790) activation were investigated. The results confirm previous observations showing that trans-4 (aminomethyl)cyclohexane-1-carboxylic acid at relatively low concentrations enhances the activation rate of Glu1-plasminogen but not that of Lys77 plasminogen. At higher concentrations both Glu1- and Lys77-plasminogen activation are inhibited. The concentration interval for the inhibition of urokinase catalysed reactions is shown to be very different from that of the tissue plasminogen activator system. Evidence is presented indicating that binding to the active site of urokinase (KD = 2.0 mM) is responsible for the inhibition of the urokinase system, binding to the active site of tissue-plasminogen activator is approx. 100-fold weaker, and inhibition of the tissue-plasminogen activator system, when monitored by plasmin activity, is mainly due to plasmin inhibition. Poly-D-lysine (Mr 160 000) causes a marked enhancement of plasminogen activation catalysed by tissue-plasminogen activator but not by urokinase. Bell-shaped curves of enhancement as a function of the logarithm of poly-D-lysine concentration are obtained for both Glu1- and Lys77-plasminogen activation, with a maximal effect at about 10 mg/litre. The enhancement of Glu1-plasminogen activation exerted by trans-4-(aminomethyl)cyclohexane-1-carboxylic acid is additive to that of poly-D-lysine, whereas poly-D-lysine-induced enhancement of Lys77-plasminogen activation is abolished by trans-4-(aminomethyl)cyclohexane-1 carboxylic acid. Analogies are drawn up between the effector functions of poly-D lysine and fibrin on the catalytic activity of tissue-plasminogen activator. PMID- 2579639 TI - Regional variation and differential sensitivity of rat heart protein synthesis in vivo and in vitro. AB - In vivo, fractional rates of protein synthesis in atrial muscle of hearts taken from fed rats were 70% greater than in ventricular muscle. After 3 days starvation, atrial protein synthesis is inhibited, but the inhibition is less than in ventricles. A crude subcellular fractionation of the aqueous homogenates by centrifugation at 32000g showed that the supernatant and precipitate proteins were synthesized at the same rate in the ventricles. The fractional rates of protein synthesis and RNA/protein ratios in the right ventricle were 10% greater than in the left ventricle. Protein synthesis in both of these regions was inhibited equally by starvation. In vitro, rates of protein synthesis in atria and ventricles of anterogradely perfused rat hearts were stimulated by saturating insulin concentrations and were inhibited by starvation, but the effects in atria were smaller than in ventricles. Rates of protein synthesis in atria in vitro were 80-95% of rates in vivo. The heart therefore shows considerable regional variation in rates of protein synthesis in vivo and in vitro, and the sensitivity of protein synthesis in the various regions to interventions such as insulin and starvation differs. PMID- 2579640 TI - Synthesis of an antigenic site of native acetylcholine receptor peptide 159-169 of Torpedo acetylcholine receptor alpha-chain. AB - A region of the alpha-subunit of the nicotinic acetylcholine receptor (AChR) of the Torpedo electric organ, containing residues 161-166, has been proposed to be a major antigenic site in the native AChR protein. We report the synthesis of a peptide corresponding to residues 159-169, which contains the proposed antigenic region. In quantitative radiometric titrations, radiolabelled anti-(native AChR) antibodies from three different species, rabbit, rat and dog, exhibited considerable binding (approx. 15% relative to native AChR) to Sepharose immobilized peptide 159-169, but did not bind significantly to Sepharose immobilized unrelated proteins or peptides. Specificity was further confirmed by the finding that no rabbit anti-AChR antibodies bound to the peptide after absorption with native AChR. These data indicate that the region 159-169 contains an antigenic site that is readily accessible in solubilized native Torpedo AChR. PMID- 2579641 TI - Complexes of rat alpha 1-macroglobulin and subtilisin are endocytosed by parenchymal liver cells. AB - Rat alpha 1-macroglobulin was isolated from plasma. Gel electrophoresis of the denatured and reduced protein showed two bands, with Mr values of 163 000 and 37 000. The large subunit contained an autolytic site. This subunit was also split after reaction of the macroglobulin with trypsin. Electron microscopy showed that the macroglobulin changed towards a more compact conformation after reaction with this proteinase. Subtilisin, or alpha 1-macroglobulin, was labelled with a sucrose-containing radio-iodinated group that stays in lysosomes after endocytosis and breakdown of the tagged protein. After intravenous injection into rats, alpha 1-macroglobulin was cleared from plasma with first-order kinetics, showing a half-life of about 9 h, whereas complexes of alpha 1-macroglobulin and subtilisin were cleared with half-lives of only 3 min. Liver contained about 60% of the label at 30 min after injection of complexes. About 90% of the liver radioactivity was found in parenchymal cells isolated after perfusion of the liver with a collagenase solution. Subcellular fractionation indicated a lysosomal localization of the complexes. We conclude that endocytosis by parenchymal liver cells is the major cause of the rapid clearance of alpha 1 macroglobulin-proteinase complexes from plasma. PMID- 2579642 TI - Chloride-ion stimulation of the tonoplast H+-translocating ATPase from Hevea brasiliensis (rubber tree) latex. A dual mechanism. AB - The effect of Cl- and other anions on the tonoplast H+-translocating ATPase (H+ ATPase) from Hevea brasiliensis (rubber tree) latex was investigated. Cl- and other anions stimulated the ATPase activity of tightly sealed vesicles prepared from Hevea tonoplast, with the following decreasing order of effectiveness: Cl- greater than Br- greater than SO4(2-) greater than NO3-. As indicated by the changes of the protonmotive potential difference, anion stimulation of tonoplast H+-ATPase was caused in part by the ability of these anions to dissipate the electrical potential. This interpretation assumes not a channelling of these anions against a membrane potential, negative-inside, but a modification of the permeability of these ions through the tonoplast membrane. In addition, Cl- and the other anions stimulated the ATPase activity solubilized from the tonoplast membrane. Consequently, the tonoplast H+-pumping ATPase can be considered as an anion-stimulated enzyme. These results are discussed in relation to various models described in the literature for the microsomal H+-ATPase systems claimed as tonoplast entities. PMID- 2579643 TI - Delayed methylation and the matrix bound DNA methylase. AB - It is shown that the methylation of DNA that occurs in isolated nuclei is "delayed methylation". This methylation is not reduced in nuclei which have been pretreated with 0.2M NaCl to extract the soluble methylase suggesting that this methylation is the product of a firmly bound matrix associated DNA methylase. Evidence is provided that, like the methylase, the DNA substrate is associated with the nuclear matrix. PMID- 2579644 TI - Major acute-phase alpha(1)protein in the rat: structure, molecular cloning, and regulation of mRNA levels. AB - Rat major acute-phase alpha(1)protein (MAP) was characterized by determining its secondary structure, ligand binding and partial amino acid sequence. A cDNA clone expressing MAP and coding for the entire mature protein was isolated from a cDNA library in E. coli prepared from rat liver mRNA. By hybridization to nick translated cDNA, mRNA for MAP was found only in liver, where it increased 17-fold during acute inflammation. Constant proportions of rates of leucine incorporation into MAP over mRNA levels in liver indicated that the regulation of the synthesis of MAP is due to a change in the rate of synthesis and/or the stability of mRNA for MAP, but not the rate of its translation. PMID- 2579645 TI - Copper(II)- and iron(II)-complexes of methyl 2-(2-aminoethyl)-aminomethyl pyridine-6-carboxyl-histidinate (AMPHIS), a peptide mimicking the metal-chelating moiety of bleomycin. An ESR investigation. AB - Methyl 2-(2-aminoethyl)-aminomethyl-pyridine-6-carboxyl-histidinate (AMPHIS), a synthetic analogue of the chelating part of bleomycin (BLM), has been studied for its metal binding properties. Electron spin resonance parameters of AMPHIS-Cu(II) and BLM-Cu(II) have been found to be closely similar likewise spectra of oxygen radicals spin-adducts induced by AMPHIS-Fe(II)-O2 and BLM-Fe(II)-O2 systems. Thus, AMPHIS could constitute a very useful tool for the study of BLM mode of action. PMID- 2579646 TI - The role of charge microheterogeneity of human myelin basic protein in the formation of phosphatidylglycerol multilayers. AB - Human myelin basic protein (HBP) was fractionated into its various charge isomers by chromatography on CM-52 columns at pH 10.6. Components 1,2,3 and "8" (C-1, C 2, C-3, and C-"8") were cleanly separated. Each component was combined with phosphatidylglycerol (PG) vesicles, at neutral pH at a concentration of 30% (w/w), protein/lipid. C-1, the most cationic of the components was the most effective at inducing the formation of multilayers when studied by liquid X-ray diffraction. C-3, which differs from C-1 by 2 positive charges was less effective than C-2. C-"8" was totally ineffective since the scattering pattern with this component was no different from that of the pure lipid. Thus a seemingly small change in net charge of the protein had a dramatic effect on the ability of the protein to organize the lipid into a crystalline, multilayer arrangement characteristic of compact myelin. PMID- 2579647 TI - Cloning and expression of the cDNA coding for aequorin, a bioluminescent calcium binding protein. AB - Aequorin is a bioluminescent protein which consists of a polypeptide chain (apoaequorin), coelenterate luciferin, and bound oxygen. Aequorin produces blue light upon binding Ca2+. We have isolated six recombinant pBR322 plasmids which contain apoaequorin cDNA sequences. A mixed synthetic pBR322 plasmids which contain apoaequorin cDNA sequences. A mixed synthetic oligonucleotide probe was used to identify these cDNAs. An extract of an E. coli strain possessing the largest cDNA contained apoaequorin. This apoaequorin can be converted to aequorin in the presence of coelenterate luciferin, 2-mercaptoethanol, and O2. This cDNA is therefore apparently full-length. PMID- 2579648 TI - Ganglioside GD2 specificity of monoclonal antibodies to human neuroblastoma cell. AB - Four monoclonal antibodies (3F8, 3A7, 3G6, and 2F7) against human neuroblastoma cells have been suggested to react with surface glycolipids of these cells. In this report these monoclonal antibodies were shown to be specific to the disialoganglioside GD2 using a thin-layer chromatography (TLC)-immunostaining method. When mixed human brain gangliosides were developed by TLC in two different solvent systems and incubated with each of the monoclonal antibodies, only GD2 was stained. These antibodies also reacted with highly purified GD2 on the plate. These findings suggest that GD2 provides an antigenic site on the surface of human neuroblastoma cells. PMID- 2579649 TI - Lack of evidence for voltage dependent calcium channels on platelets. AB - Intracellular calcium was measured in human platelets using the fluorescent calcium indicator Quin 2. A concentration dependent increase was observed with thrombin. Depolarisation induced by high KCl concentrations did not alter [Ca++]i. The calcium agonist Bay K 8644 did not affect resting levels or thrombin stimulated elevation of intracellular calcium. The calcium antagonists diltiazem, verapamil and PN 200-110 did not inhibit the thrombin stimulated elevation in [Ca++]i. Pretreatment of platelets with adenylate cyclase stimulants reduced the rate and magnitude of the maximal [Ca++]i elevation due to thrombin. In addition, thrombin stimulation of 45Ca++ influx was insensitive to Bay K 8644, verapamil, diltiazem and Pn 200-110. We conclude that functional voltage sensitive calcium channels are not present on human platelets. PMID- 2579650 TI - Effect of Pseudomonas aeruginosa exotoxin-A on the synthesis and secretion of proteins in isolated rat pancreatic acini. AB - Exposure of isolated rat dispersed pancreatic acini to increasing concentrations (10 to 1000 ng/ml) of purified exotoxin-A from Pseudomonas aeruginosa resulted in a progressive inhibition of 3H-leucine incorporation into "cellular" (those remaining in the cells) and "secretory" (those released into the medium) proteins. With each concentration of exotoxin-A, magnitude of reduction was found to be greater for the "secretory" proteins than that observed for the "cellular" proteins. Thus, in the presence of 250 ng/ml of exotoxin-A, a dose that produced maximal inhibition in protein synthesis, 3H-leucine incorporation into "cellular" and "secretory" proteins was found to be decreased by about 19 and 50%, respectively, when compared with the corresponding basal controls. Release of trypsinogen, chymotrypsinogen and amylase from the isolated pancreatic acini was also inhibited by high doses of exotoxin-A. However, whereas the exotoxin concentration of 1000 ng/ml, caused a near complete inhibition of chymotrypsinogen release, trypsinogen and amylase secretion were decreased by 40 and 50%, respectively. It is concluded that in isolated pancreatic acini, exotoxin-A inhibits the synthesis and secretion of proteins. PMID- 2579651 TI - Occurrence of the methylisobutylxanthine-stimulated cyclic GMP binding protein in various rat tissues. AB - A new type of cGMP binding protein, the activity of which is characteristically stimulated by methylisobutylxanthine, has been previously discovered in rat lung and platelets (Hamet, P. and Coquil, J.F. (1978) J. Cyclic Nucleotide Res. 4, 281 290). In the present study, we demonstrate the occurrence of this protein in soluble extracts of a variety of rat tissues fractionated by a DEAE-Sepharose chromatography. In several tissues (spleen, lung and brain) the binding activity of this protein was of the same order of magnitude as that of the cGMP-dependent protein kinase. PMID- 2579652 TI - Expression of long terminal repeat (LTR) sequences in carcinogen-induced murine skin carcinomas. AB - RNA sequences homologous to the Long Terminal Repeat (LTR) sequence of Moloney Murine Leukemia Virus proviral DNA are expressed in murine squamous cell carcinomas of the skin induced by chemical carcinogens. These transcripts range in size from 8.2 to less than 2.4 kb but their size profile varies between individual tumors. These RNAs are not detected in the poly A+ RNA fraction obtained from the epidermis of control mice or carcinogen induced skin papillomas. The poly A+ RNAs from the livers and spleens of some of the mice with skin carcinomas also revealed LTR related sequences, whereas these RNAs were not detected in the livers and spleens of control mice or of carcinogen-treated mice that did not develop carcinomas. Thus, chemical carcinogenesis in mouse skin is associated with constitutive expression of endogenous retrovirus related sequences in the carcinomas as well as in certain apparently normal host tissues. PMID- 2579653 TI - gamma-Endorphin generating endopeptidase in rat brain: subcellular and regional distribution. AB - beta-Endorphin is converted into the biologically active fragment gamma-endorphin by an endopeptidase which we term "gamma-endorphin generating endopeptidase". Subcellular and regional distributions of this endopeptidase activity in rat brain were studied by a newly developed assay. After subcellular fractionation of rat brain tissue gamma-endorphin generating endopeptidase activity was predominantly recovered in the cytosolic fraction. A 10 to 15 fold lower activity was present in synaptosomes, mitochondria and synaptic membranes. Hardly any endopeptidase activity was detected in nuclei and myelin. The endopeptidase activity in cytosolic and particulate fraction was found throughout brain, pituitary and spinal cord in a rather homogeneous fashion. Cytosolic activity in all brain parts was 10 to 15 fold higher than the activity in the particulate fraction. It is suggested that rather the beta-endorphin distribution than the endopeptidase is restricting for gamma-endorphin production in certain brain parts. PMID- 2579654 TI - Dihydropyridine sensitive calcium channels in a smooth muscle cell line. AB - The pharmacological properties of voltage sensitive calcium channels (VSCC) were examined in a rat aortic smooth muscle cell line (A10). The inorganic VSCC blockers Co2+ and Cd2+ blocked 45Ca2+ uptake into these cells in both 5 mM K+ and 50 mM K+ (depolarizing) conditions. The organic VSCC antagonists nitrendipine, nimodipine, D-600 and diltiazem also blocked 45Ca2+ uptake at low concentrations. The relative potencies of blockade were similar to those found in intact vascular smooth muscle. The VSCC "agonist" BAY K8644 enhanced 45Ca2+ uptake and this effect could be reversed by nitrendipine. These results indicate that A10 cells possess VSCC and that these VSCC behave similarly to those in authentic smooth muscle. PMID- 2579655 TI - Identification and characterization of a polyadenylated small RNA (s-poly A+ RNA) in dinoflagellates. AB - A 104 nucleotide-long small RNA, referred to as s-poly A+ RNA, containing 30 adenosine residues on its 3' -end was found in dinoflagellates, purified and its nucleotide sequence was determined. The sequence is: (sequence text) The polyadenylation signal AAUAAA was not found in this RNA; this result indicates that the 30 nucleotide-long poly A on the 3' -end is either coded for by this gene, or the poly A chain is added on this small RNA by a mechanism different from that for polyadenylation of messenger RNAs. Two polyadenylated small RNAs identified previously were implicated in differentiation of chicken heart muscle cells (Deshpande, A. K., Jakowlew, S. B., Arnold, H., Crawford, P. A. and Siddiqui, M. A. Q. (1977) J. Biol. Chem. 252, 6521-6527), and in brain specific mRNA transcription (Sutcliffe, J. G., Milner, R. J., Gottesfeld, J. M. and Lerner, R. A. (1984) Nature 309, 237-241). This RNA is the first polyadenylated small RNA to be sequenced. PMID- 2579656 TI - Analysis of chromatin of the brain of young and old rats by nick-translation. AB - Chromatin of the brain of young (22-23 week) and old (118-119 week) rats has been analysed by nick-translation reaction following its digestion by DNaseI, EcoRI, MspI and HpaII. The incorporation of (3H)-dTMP in the old is only about 50 percent of that of the young. The difference in the incorporation following digestion of nuclei by MspI and HpaII that quantitate the degree of methylation of internal cytosines in the 5' CCGG 3' sequences, is nearly two-fold higher in the old. These data indicate that the chromatin undergoes increasing condensation as a function of age. One of the contributory factors may be increasing methylation of DNA. This may decrease the active fraction of chromatin. PMID- 2579657 TI - Mammalian tachykinin-induced hydrolysis of inositol phospholipids in rat brain slices. AB - The mammalian tachykinins substance K, neuromedin K and substance P stimulated inositol phospholipid hydrolysis in paired coronal sections through the rat brain. In contrast, none of these peptides had any effect on either basal or forskolin-stimulated cyclic AMP levels. The present results therefore implicate inositol phospholipid hydrolysis as a possible second messenger system mediating the effects of substance K and neuromedin K in addition to substance P. PMID- 2579658 TI - Conformationally restricted cyclic analogues of substance P: insight into the receptor binding process. AB - Three new cyclic substance P analogues were prepared to examine the possible role of a pseudocyclic turn structure for receptor recognition. In the guinea pig isolated ileum [Cys5, Cys11]-SP5-11-NH2 and [Cys6, Cys11]-SP5-11-NH2 were inactive at concentrations up to 100 microM, while [Cys5, Cys6, Nle11]-SP was a weak agonist. The order of relative affinities on the rat brain radioreceptor assay was as follows: [Cys5, Cys6, Nle11]-SP greater than [Cys5, Cys11]-SP5-11 NH2 greater than [Cys6, Cys11]-SP5-11-NH2. We interpret these results to indicate that a pseudocyclic structure of the 5-11 sequence may not be an important factor involved in the receptor recognition of substance P. PMID- 2579659 TI - Bleomycin control of transplasma membrane redox activity and proton movement in HeLa cells. AB - Bleomycin, tallysomycin A, tallysomycin S10b and copper-bleomycin have been tested for their capacity to inhibit the transplasma membrane electron transport and associated proton release by HeLa cells. Transplasma membrane redox activity is measured using reduction of external ferricyanide by the cells. At 75 micrograms/ml bleomycin, tallysomycin A and tallysomycin S10b gave a maximum of 65% inhibition of the ferricyanide reduction rate; half-maximum inhibition was observed at 30 micrograms/ml. The copper-bleomycin complex was slightly more effective as an inhibitor with half-maximum inhibition at 20 micrograms/ml. Survival of cells after 1 hr of drug treatment was 50% at 25 micrograms/ml for bleomycin and copper-bleomycin and at 75 micrograms/ml for tallysomycin A. Tallysomycin A and tallysomycin S10b gave 75 to 83% inhibition of ferricyanide induced proton extrusion, respectively at 50 micrograms/ml, whereas bleomycin and copper-bleomycin appeared to be slightly less effective with 50 to 60% inhibition, respectively, at 50 micrograms/ml. In all aspects studied, which included transplasma membrane ferricyanide reduction, ferricyanide-induced proton release, and cell survival, there were significant effects by these compounds on HeLa cells in the range of 25-50 micrograms/ml. PMID- 2579660 TI - Tricyclic antidepressant inhibition of depolarization-induced uptake of calcium by synaptosomes from rat brain. PMID- 2579661 TI - Neonatal lupus erythematosus occurring in one fraternal twin. Serologic and immunogenetic studies. AB - Neonatal lupus erythematosus (LE) is a syndrome that is manifested by LE skin lesions and/or congenital heart block, occurring in infants at, or shortly after, birth. The syndrome is believed to be caused by transplacental passage of an IgG antibody, usually the anti-Ro (SS-A) antibody, from the mother to the infant. Although the mother may have a connective tissue disease or may be healthy, the common characteristic is the presence of maternal circulating anti-Ro antibody. It has been believed that the HLA determinants demonstrated in children who have neonatal LE were not a factor in the expression of the syndrome. We report the occurrence of neonatal LE, manifested by photosensitivity and discoid LE skin lesions, in one fraternal twin. HLA studies of this affected twin demonstrated the presence of DR3. Anti-Ro antibody was present in the mother, but was not present in either child at 4 months post-delivery. HLA determinants may be involved in the expression of disease in neonates who have been exposed to the anti-Ro antibody. Furthermore, the presence of circulating antibodies in the unaffected twin causes us to question the assumption that the anti-Ro antibody is the causative factor for the occurrence of tissue injury in children with neonatal LE. PMID- 2579662 TI - Response of the acute-phase reactants, C-reactive protein and serum amyloid A protein, to antibiotic treatment of Whipple's disease. PMID- 2579664 TI - Hypoxic ventilatory drive in the dog under Althesin anaesthesia. PMID- 2579663 TI - The whole blood oxygen affinity in normal human newborns: II) P50, n value and related parameters. AB - The cord blood from 82 normal newborns (48 males and 34 females) has been extensively investigated, to check p50, cooperativity and related parameters. The most important results are the following: Neonatal p50 is slightly above 20 torr, in good agreement with the literature data, but this value refers to the p50 "CO free" (T50); otherwise, the original p50 is slightly less than 22 torr, a value which is not indicative enough, because neonatal blood contains a consistent excess of Hb-CO. Either this CO-excess and the low p50 value seem to be mainly depending on the low binding capacity of Hb-F with DPG, even if further studies are still necessary at regard. The empirical factor correcting adult p50 to T50 is -0.27, a value which must be increased to -0.36 for neonatal blood. Multiple gas analyses of the samples indicate that oxygen transport is a very complicate equilibrium involving pH, CO2, bicarbonate balance and other factors. A complete statistical analysis of the data has been carried out and the main result indicates that oxygen assumption favours CO2 releasing and vice versa, a phenomenon already well known and globally called "Bohr effect". PMID- 2579665 TI - Chemotherapy of metastatic seminoma. AB - Response to chemotherapy and survival was retrospectively analyzed in 28 patients with bulky retroperitoneal and disseminated seminoma treated between 1977 and 1983. The median age was 41 years (range: 23-52). All patients had histological evidence of pure testicular seminoma, however, 14 patients revealed moderate increases of human beta-chorionic gonadotropin levels. Prior radiotherapy had been given to 9/28 (32%) patients. Treatment consisted of at least four courses of simultaneous or sequentially alternating therapy with cisplatin, vinblastine, bleomycin plus/minus adriamycin (PVB +/- A), administration of ifosfamide or combination therapy with ifosfamide/cisplatin (IFS/DDP) or ifosfamide/etoposide (IFS/ETP). Twenty-five of 28 patients (89%) achieved a complete (CR), and 3/28 patients a partial remission. Relapse occurred in 1/8 CR patients after adjuvant postchemotherapeutic irradiation, and in 1/11 patients without any further radiotherapy. So far, 23/28 patients (82%) are free of disease after a median follow-up of 28+ (14+----82+) months. Marked myelosuppression was observed in previously irradiated patients, mainly after PVB +/- A therapy. In two patients, transient nephrotoxicity developed after PVB and IFS/DDP, respectively. After PVB +/- A chemotherapy, three patients revealed polyneuropathy, paralytic subileus and bleomycin-induced pneumonitis, respectively. In conclusion, the present series suggests a high probability of continuous CR in even bulky retroperitoneal and widespread metastatic seminoma. So far, no definite conclusions can be made on the therapeutic superiority of one of the different chemotherapeutic regimens used. However, this preliminary experience suggests that the combination of ifosfamide and etoposide or cisplatin may prove less toxic than sequentially alternating or simultaneous PVB +/- A chemotherapy. PMID- 2579666 TI - Bleomycin and misonidazole cytotoxicity. AB - Chinese hamster ovary (CHO) cells were exposed in vitro to combinations of bleomycin and misonidazole under hypoxic conditions. Only one drug was present at any given time and cells were washed before being exposed to the second drug. Both drugs induced potentially lethal damage (PLD). This damage was repaired under hypoxic conditions very rapidly, and bleomycin-induced PLD was repaired more rapidly than misonidazole-induced PLD. If, after the combined treatment, cells are kept in hypoxia, much of the damage can be repaired. PMID- 2579668 TI - Increased DNA synthesis of uninvolved psoriatic epidermis is maintained in vitro. AB - Clinically uninvolved psoriatic epidermis shows increased DNA synthesis in vivo. We have studied the DNA synthesis of cultured keratinocytes from uninvolved psoriatic skin. Trypsinized epidermal cells were plated on plastic dishes pre coated with bovine collagen type I. In initial studies, normal human serum was found to be superior to fetal bovine in supporting the growth of human epidermal keratinocytes. Furthermore, keratinocyte cultures established in the presence of normal human serum produced large keratin proteins (68,000 daltons) indicating that the terminal steps in cell differentiation can occur in vitro. In subsequent experiments keratinocyte cultures were grown in medium supplemented with 10% normal human serum. Confluent cultures of keratinocytes from uninvolved psoriatic epidermis had an increased DNA synthesis determined both as the incorporation of [3H]thymidine and as the autoradiographic labelling index. The DNA synthesis of both normal and psoriatic keratinocyte cultures increased in response to incubation in medium with 10% psoriatic serum. The ability of keratinocytes from uninvolved psoriatic epidermis to maintain an increased DNA synthesis suggests the presence of an inherent defect within the population of epidermal keratinocytes in psoriasis. Such a culture system can be used as an in vitro model for the study of psoriasis. PMID- 2579667 TI - Cell selection from a murine tumour using the fluorescent probe Hoechst 33342. PMID- 2579669 TI - Ichthyosis linearis circumflexa: morphological and biochemical studies. AB - Extensive morphological and biochemical studies were carried out on two sibling cases of ichthyosis linearis circumflexa. The condition was found to be similar to psoriasis in the following ways: effectiveness of PUVA therapy, psoriatic changes on light and electron microscopy, high urinary polyamine levels, elevation of several enzyme activities in the scales, and a remarkable change in keratin molecules. These results may reflect an increased epidermal proliferation with a reduced epidermal transit time, as occurs in psoriasis. PMID- 2579670 TI - Isoquinoline is a possible anti-psoriatic agent in coal tar. AB - Isoquinoline has been identified as a component of coal tar which causes interfollicular regions of parakeratotic stratum corneum in mouse tail epidermis to become orthokeratotic, with concomitant production of a granular layer. In this respect it behaves similarly to coal tar itself, and isoquinoline may contribute to the anti-psoriatic activity of coal tar. PMID- 2579671 TI - Prophylaxis of thromboembolism in pregnancy: an alternative. AB - Twenty-six pregnancies in women who had one or more episodes of thromboembolism in the past were managed by a regimen in which routine antenatal prophylactic anticoagulation was not given, apart from during delivery which was covered with intravenous infusion of dextran 70. After delivery, these patients received either subcutaneous heparin for 6 weeks or subcutaneous heparin for 1 week, followed by 5 weeks of warfarin. One patient (4%) possibly developed an episode of thromboembolism in the antenatal period. There were no episodes of postnatal thromboembolism. There were two spontaneous mid-trimester abortions and no perinatal losses. There were no significant complications or reactions related to the use of dextran, heparin or warfarin. PMID- 2579672 TI - Photocoagulation for peripheral neovascularisation in diabetes. AB - A study of 90 eyes in 72 diabetic patients with peripheral retinal neovascularisation treated by photocoagulation indicated that the subsequent development of further peripheral or disc new vessels is infrequent if panretinal photocoagulation is the initial treatment procedure. Focal or sectorial treatment may be considered only if a small area of neovascularisation is present initially and provided regular follow-up can be guaranteed. PMID- 2579673 TI - Comparison of the effects of Anemonia toxin II on sodium and gating currents in frog myelinated nerve. AB - Na+ and gating currents were measured in myelinated frog nerve fibres without and in the presence of 7 microM Anemonia toxin II in the extracellular solution. From the experiments, kinetic parameters of Na+ currents and of gating charge displacements during ('on' response) and after ('off' response) depolarizations were determined. The following parallel modifications of Na+ currents and charge displacements by Anemonia toxin II were observed: the toxin reduces the maximum Na+ permeability and the 'on' charge displacement; Na+ activation and 'on' charge displacement become faster; Na+ inactivation and the decline of the 'off' charge displacement with increasing pulse duration (charge immobilization) are prolonged; slow components of 'on' charge displacements are diminished. The observations support the notion that the fast 'on' charge displacement is connected with the process of Na+ activation, while Na+ inactivation is linked to charge immobilization. Our experiments suggest that slow 'on' charge displacements during longer depolarizations are correlated with the process of Na+ inactivation. PMID- 2579674 TI - Calcium- and voltage-activated potassium channels in adrenocortical cell membranes. AB - Current flowing through single Ca- and voltage-activated K channels has been recorded from cell-attached and inside-out excised membrane patches of cultured Y 1 adrenocortical cells. In intact cells, single-channel current amplitude and the time a channel stays in the open state increase with membrane depolarization. In excised patches bathed in symmetrical 130 mM K solutions, single-channel conductance is 170 pS. This value is constant in the membrane potential range of +/- 50 mV but decreases at larger hyper- and depolarizations. Channel open probability is heavily influenced by the concentration of ionic Ca at the inner surface of the membrane in the range between 0.01 and 10 microM. When internal Ca concentration is close to 0.01 microM, channels are usually closed even at large depolarizing voltages. With larger Ca concentrations, channel open probability increases and its voltage dependence is greater. These channels are uniformly distributed in the plasma membrane, since one to four channels were seen in more than 99% of the patches isolated in this study. There are previous reports suggesting a role for calcium ions in the secretory response of adrenocortical cells to ACTH. Therefore, it is possible that, as in other endocrine cells, these K channels modulate Ca influx across the plasma membrane and thus contribute to regulate steroid biosynthesis and release. PMID- 2579675 TI - Effects of ionophore A23187 and lanthanum on pepsinogen secretion from frog esophageal mucosa in vitro. AB - The role of Ca2+ in the mediation of pepsinogen secretion from frog esophagus was investigated by means of ionophore A23187 and LaCl3. The esophageal mucosa from Asian bullfrog Rana tigerina was mounted in a double-chamber system to preserve its polarity and was incubated in a medium containing 1.5 mM CaCl2. Pepsinogen secreted was measured and expressed as % of total. The basal secretion averaged 3.5%/h. Bethanechol (25 microM), dibutyryl-cAMP (10 mM), ionophore A23187 (30 microM) and 3-isobutyl-1-methylxanthine (0.1 mM) increased the secretion to 8.7, 7.4, 7.1 and 6.8%, respectively. The stimulatory effect of bethanechol and of dibutyryl-cAMP were not affected by removing the exogenous Ca2+ with EGTA. The basal secretion was, however, reduced by 50% when Ca2+ in the incubation medium was lowered to 20 microM. At this low Ca2+ concentration, ionophore A23187 not only lost its stimulatory effect but also diminished the stimulation caused by bethanechol and dibutyryl-cAMP. While LaCl3 at 1 mM had no effect on basal and bethanechol-stimulated secretion, at 10 mM it abolished the stimulation evoked by bethanechol or dibutyryl-cAMP. The conclusions are: (1) both Ca2+ and cAMP are involved in the mediation of pepsinogen secretion from frog esophagus, (2) basal secretion is dependent on extracellular Ca2+, whereas bethanechol-stimulated secretion is not, (3) in the plasma membranes of peptic cells may exist a distinct Ca2+ pool (La3+-and ionophore A23187-sensitive) which is involved in the stimulated pepsinogen secretion. PMID- 2579676 TI - A quantitative explanation of the effects of some alcohols on gramicidin single channel lifetime. AB - The effects of n-decanol, n-hexadecanol, n-octyl(oxyethylene)3 alcohol and cholesterol on gramicidin single-channel lifetime in planar lipid bilayers have been determined. The bilayers used were formed from a solution of monoolein in squalene. Measurements have also been made of the above compounds' effects on membrane thickness (as measured by electrical capacity and optical reflectance technique) and surface tension (as derived from bulk interfacial tension and bilayer-lens contact angle measurements). The reduction in single-channel lifetime caused by the n-alkanols may be accounted for quantitatively in terms of the effects of these compounds on bilayer thickness and surface tension. The n octyl(oxyethylene)3 alcohol caused an increase in single-channel lifetime which is also consistent with the thickness/tension theory. The reduction in channel lifetime caused by cholesterol, however, was much larger than would be predicted from its effects on bilayer thickness and surface tension. PMID- 2579678 TI - Uptake and degradation of insulin and alpha 2-macroglobulin-trypsin complex in rat adipocytes. Evidence for different pathways. AB - The cell association and degradation of insulin and alpha 2-macroglobulin-trypsin complex were measured in rat adipocytes with or without various inhibitors in the attempt to clarify whether the two ligands were taken up by the same or by different pathways. Several inhibitors, and particularly those of membrane traffic, lysosomal function and transglutaminase activity, affected the two ligands differently. Thus, chloroquine (100 microM) reduced both the uptake of alpha 2-macroglobulin X trypsin and its receptor-mediated degradation by about 70%. In contrast, the uptake of insulin was increased 2-3-times and the receptor mediated degradation was only slightly reduced. Methylamine (10 mM) and ammonium chloride (10 mM) reduced degradation of alpha 2-macroglobulin X trypsin markedly without affecting that of insulin. Leupeptin (100 microM) increased uptake and reduced degradation of alpha 2-macroglobulin X trypsin without affecting insulin. Dansylcadaverine (500 microM) almost abolished uptake and degradation of alpha 2 macroglobulin X trypsin but had little effect on insulin. Moreover, uptake and degradation of alpha 2-macroglobulin X trypsin was much more sensitive than insulin to the action of metabolic inhibitors such as dinitrophenol and cyanide. The results show that the two ligands are taken up by functionally different systems. In addition, they support the hypothesis that lysosomes play a relatively minor role in the receptor-mediated degradation of insulin. PMID- 2579677 TI - Leupeptin as a tool for the detection of the sites of catabolism of rat high density lipoprotein apolipoproteins A-I and E. AB - Leupeptin, an inhibitor of lysosomal cathepsin activity, was injected intravenously into male rats. Tissues obtained from leupeptin-treated animals showed a depressed cathepsin activity when compared with tissues from saline treated control animals. Leupeptin treatment did not change the hepatic activities and subcellular distribution of marker enzymes for mitochondria, microsomes and plasma membranes. Hepatic lysosomal cathepsin activity was specifically inhibited, but the subcellular distribution of all lysosomal marker enzymes tested was changed, indicating the occurrence of enlarged lysosomes in the leupeptin-treated animals. No significant differences were observed in the serum concentrations of protein, cholesterol, cholesteryl esters, phospholipids and apolipoproteins A-I, A-IV and E between leupeptin-treated rats and control animals. When radioiodinated asialofetuin was injected intravenously, the radiolabel was retained for an extended period of time in the liver of leupeptin treated animals, indicating diminished catabolism of this protein in the liver. When rat high-density lipoprotein, labelled specifically in the apolipoprotein A I or E moiety was injected intravenously, only the kidneys and the liver showed a leupeptin-induced accumulation of radioactivity. These studies provide evidence for an important contribution of the kidneys and the liver to the in vivo catabolism of high-density lipoprotein apolipoproteins, using a method completely different from sugar-containing labelling compounds. PMID- 2579679 TI - [Different sensitivities of two mechanisms of excitation waves in heart tissue to anti-arrhythmia agents--blockers of fast sodium currents]. AB - In experiments with rabbit ventricular tissue sensitivity of two kinds of spiral wave sources of excitation to fast sodium current inhibition was compared. These spiral wave sources were circulation in a ring around an obstacle and circulation in tissue without an obstacle (reverberator). It was observed that after application of antiarrhythmic drugs lidocaine or mexiletine there was a prominent growth of cycle length of reverberator during first few seconds of circulation and a little change of cycle length for the circus movement around obstacle. It is proposed that different sensitivity of both kinds of spiral wave sources to antiarrhythmic drugs can be used for their distinguishing in clinical practice. PMID- 2579680 TI - [Resistance of various protein channels to proteolytic degradation]. AB - The influence of some proteolytic enzymes on the properties of the ionic channels induced in the lipid bilayer by three different toxic proteins was studied. It was found that pronase and trypsin did not decrease the conductance of the membranes modified by melittin, alpha-staphylotoxin and latrotoxin and changed its cation-anion selectivity. The dependence of melittin-channels selectivity on the medium pH was investigated. It was suggested that the carbonyl groups of peptide bond take part in defining cation selectivity of the melittin channel. PMID- 2579681 TI - Cerebrospinal fluid and plasma monoamines and their metabolites in euthymic bipolar patients. AB - In a search for trait markers in manic-depressive illness, we studied cerebrospinal fluid (CSF) and plasma monoamines and their metabolites in 25 lithium-treated euthymic bipolar patients (12 of whom provided unmedicated samples) and 30 normal volunteers. No group differences were found. Lithium treatment showed a trend to increase CSF hydroxy-indoleacetic acid (HIAA) (p = 0.05). Dopaminergic and serotonergic metabolites were highly correlated in the CSF of all three groups. We found no evidence of a trait marker for manic depressive illness among CSF monoamines and their metabolites. PMID- 2579683 TI - Single chloride-selective channels active at resting membrane potentials in cultured rat skeletal muscle. AB - The patch-clamp technique was used to characterize channels that could contribute to the resting Cl-conductance in the surface membrane of cultured rat skeletal muscle. Two Cl- -selective channels, in addition to the Cl- -selective channel of large conductance described previously (Blatz and Magleby, 1983), were observed. One of these channels had fast kinetics and a conductance of 45 +/- 1.8 pS (SE) in symmetrical 100 mM KCl. The other had slow kinetics and a conductance of 61 +/ 2.4 pS. The channel with fast kinetics typically closed within 1 ms after opening and flickered between the open and shut states. The channel with slow kinetics typically closed within 10 ms after opening and displayed less flickering. Both channels were active in excised patches of membrane held at potentials similar to resting membrane potentials in intact cells, and both were open a greater percentage of time with depolarization. Under conditions of high ion concentrations, both channels exhibited nonideal selectivity for Cl- over K+ with the permeability ratio PK/PCl of 0.15-0.2. Additional experiments on the fast Cl- channel indicated that its activity decreased with lowered pHi and that SO2-4 and CH3SO-4 were ineffective charge carriers. These findings, plus the observation that the fast Cl- channel was also active in membrane patches on intact cells, suggest that the fast Cl- channel provides a molecular basis for at least some of the resting Cl- conductance. The extent to which the slow Cl- channel contributes is less clear as it was typically active only after excised patches of membrane had been exposed to high concentrations of KCl at the inner membrane surface. PMID- 2579682 TI - Embryotoxic drugs. PMID- 2579684 TI - Simple model can explain self-inhibition of red cell anion exchange. AB - Ion translocation in red cell anion exchange is assumed to occur by means of an alternating access mechanism, in which a critical binding site for the transported ion alternates between two conformational states, each accessible from only one side of the membrane. If this alternating site is located within the transport protein at some distance from one or both surfaces of the membrane, an access channel is required to connect the alternating site to the adjacent bulk solution. This automatically leads to inhibition of transport at high concentrations of the transported ion because release of the ion from the alternating site can occur only via unoccupied channel sites. PMID- 2579685 TI - Stochastic behavior of a many-channel membrane system. AB - A stochastic theory of channel-gating transitions is developed for a stationary system with many channels, with applications to patch-clamp single-channel experiments. Exact probability density and distribution functions for closed times, open times, and first transit times in an N-channel system are obtained in terms of N and the solutions for a one-channel system. Once N is determined, the expressions derived here can be used to analyze data records that are crowded by many channel openings and where multilevel events are common. The three-state model is treated as a specific example. Computer simulations of three-state models indicate that the equations derived here can be used to recover useful information from crowded single-channel current records. The simulations also revealed some of the limitations to the usefulness of these equations. The probability that a channel that has not opened is in a particular closed state was examined as a function of time. This analysis led to a useful limit where the distribution of unopened channels between various closed states is constant in time. This limit simplifies the mathematical treatment of closed-time probabilities, and provides a general method for the analysis of many-channel systems when channels open infrequently. PMID- 2579687 TI - Interaction of K+ ion with the solvated gramicidin A transmembrane channel. AB - Using Urry's gramicidin A (GA) atomic coordinates and ab into calculations, the interaction energies of a K+ ion with GA are examined. From these energies the values of the fitting parameters are obtained for 6-12-1 atom-atom pair potentials. The potential of the GA channel as experienced by the ion is analyzed in detail. An energy profile of the K+ ion in the GA channel is obtained by analyzing iso-energy maps. Using Monte Carlo simulations, the energy profiles of the K+ ion with the solvated GA channel are analyzed and the hydration structures in the presence of the K+ ion are studied. PMID- 2579686 TI - Demyelination as a test for a mobile Na channel modulator in frog node of Ranvier. AB - We found previously that the external surface of frog skeletal muscle fibers can be irreversibly modified by treatment with the amino group-specific reagent, trinitrobenzene sulfonic acid (TNBS). Reaction of the muscle membrane with TNBS permanently shifts the potential dependence of the sodium channel inactivation gating process, h infinity, to more hyperpolarized potentials. The experiments presented here show nearly identical effects on the sodium currents of voltage clamped frog node of Ranvier in the presence of TNBS. In contrast to the results in muscle, in myelinated nerve the voltage dependence of sodium-channel inactivation returns rapidly to control values following a brief exposure to TNBS. We have used partial demyelination to test the hypothesis that recovery of the normal voltage dependence for h infinity following TNBS treatment is due to lateral diffusion of reacted groups away from the sodium channels in the node. We find that increasing the membrane area exposed to TNBS by partial demyelination greatly slows reversal of the TNBS effects. This result suggests that a modifiable membrane component that affects sodium channel gating is mobile in the plane of the membrane and can rapidly diffuse between nodal and internodal regions. PMID- 2579688 TI - The effects of recombinant-DNA-derived interferons on the growth of myeloid progenitor cells. AB - Interferons (IFNs) have been shown to have significant effects on hematopoietic cell growth. Previous studies defining these effects have utilized mouse and human alpha-, beta-, and gamma-IFN isolated from supernatants of stimulated cells. Despite purification, the possible presence of other lymphokines and soluble factors remains a concern. In this study, the effects of gene-cloned alpha- and gamma-IFN on colony-forming units of granulocyte/macrophage (CFU-GM) progenitors cultured from the peripheral blood of normal volunteers were examined. In addition, blast cell colonies from one patient with acute myelogenous leukemia (AML) were studied. The growth of normal CFU-GM and AML blast cell colonies was inhibited in a dose-dependent manner by gamma- and alpha IFN. gamma-IFN was ten to 100 times more potent than alpha-IFN in that this species of IFN reduced colony formation by greater than 50% at concentrations of less than 15 antiviral U/mL. The effects of gamma-IFN were neutralized by a monoclonal antibody specific for gamma-IFN. These in vitro studies indicate that human gamma-IFN may be an important modulator of myelopoiesis. Although these data indicate a possible efficacy of gamma-IFN in the treatment of AML, the in vitro results should be considered for their in vivo significance. PMID- 2579689 TI - The effect of 5-azacytidine and its analogues on blast cell renewal in acute myeloblastic leukemia. AB - Blast cells from patients with acute myeloblastic leukemia were exposed to 5 azacytidine (5-aza) and its analogues 5-aza 2'-deoxycytidine (5-aza-dr) and 6 azacytidine (6-aza). Simple negative exponential survival curves were obtained for the three drugs, but the sensitivity varied; 5-aza-dr was most toxic, 6-aza was least toxic, and 5-aza was intermediate. Colonies surviving drug exposure were replated; 5-aza and 5-aza-dr were found to increase secondary plating efficiency, whereas 6-aza was inactive. The findings provide indirect evidence for a role for DNA methylation in the regulation of blast cell self-renewal. PMID- 2579690 TI - Immunocytochemical study of the binding of fibrinogen and thrombospondin to ADP- and thrombin-stimulated human platelets. AB - We have used immunogold staining to locate thrombospondin (TSP) on thrombin activated human platelets, and have compared its distribution with that of fibrinogen (or fibrin) on thrombin- and ADP-stimulated platelets. To do this, isolated platelets were incubated with monospecific antibodies to TSP or fibrinogen (fib) and the bound IgG located with a second antibody adsorbed to gold particles. Thrombin-induced secretion in Tyrode-Ca2+ was followed by both anti-TSP and anti-fib binding, with large clusters of gold particles observed on the platelet surface. Little or no labeling was observed on unstimulated platelets with either antibody. When secretion was effected in Tyrode-EDTA, anti TSP IgG still bound to the activated platelets, but the number of particle clusters was significantly reduced. Little binding of anti-fib IgG now occurred. Platelets activated with ADP in the presence of added fib, and subsequently incubated with anti-fib IgG, showed small particle clusters over the whole platelet surface. Thrombin-stimulated platelets from two patients with thrombasthenia bound anti-TSP IgG similarly to normal platelets activated in Tyrode-EDTA. No anti-fib binding occurred. Our results suggest that fib and TSP bind to specific domains on the stimulated platelet membrane. Such sites may be responsible for the mediation of platelet surface contact interactions. PMID- 2579691 TI - Ultrastructural localization of human platelet thrombospondin, fibrinogen, fibronectin, and von Willebrand factor in frozen thin section. AB - We have investigated the localization of thrombospondin (TSP), fibrinogen, fibronectin, and von Willebrand factor in human platelets by transmission electron microscopy of antibody-stained ultrathin frozen sections. In negatively stained thin sections, alpha granules were identified on the basis of their smooth, roughly spherical shape, size, single limiting electron-lucent 100 A membrane, and frequent presence of electron-dense nucleoid. In contrast, mitochondria exhibited characteristic double membranes and cristae. Sections were separately stained with affinity-purified polyclonal antibodies to these proteins as well as with three monoclonal anti-TSP antibodies. Antibody specificity was documented in radioimmunoassays, by immunofluorescent cross-blocking, and by staining of bands of appropriate mobility in Western blots of whole platelets. Bound antibody was visualized using a 5-nm colloidal gold-avidin conjugate. In resting cells, staining of virtually all alpha granules was observed for all four proteins. In contrast, consistent staining was absent from other organelles, including plasma membranes, mitochondria, and vacuolar structures that may represent the open canalicular system. PMID- 2579692 TI - The modulated expression of Mo5, a human myelomonocytic plasma membrane antigen. AB - Mo5 is a 94-kd protein antigen expressed by human peripheral blood monocytes, neutrophils, and by all bone marrow myeloperoxidase-positive myeloid precursors (promyelocytes, myelocytes, metamyelocytes, and bands). Mo5 is borne by the malignant cells of 74% of patients (N = 27) with acute monocytic leukemia (French American-British [FAB] group M4, M5), and 50% of patients (N = 38) with acute granulocytic leukemia (FAB M1, M2, and M3). Nonmyeloid cells in peripheral blood and bone marrow are Mo5-negative. The surface expression of Mo5 by myeloid cells is modulated by several experimental conditions: Exposure of neutrophils to calcium ionophore (1 mumol/L, 37 degrees C, ten minutes) under conditions resulting in degranulation of specific granules produces a three- to fourfold increase in the plasma membrane density of Mo5 antigen. This suggests that, in neutrophils, there is an intracellular pool of Mo5 antigen, which may be associated with specific granules, and that granule-associated Mo5 is translocated to the plasma membrane upon degranulation. Conversely, incubation of monocytes, neutrophils, U-937, and Mo5-positive leukemia cells in medium containing anti-Mo5 monoclonal antibody results in a significant decrease in surface Mo5 expression. This loss of surface Mo5 is a rapid, temperature dependent process (occurring within 30 minutes at 37 degrees C) that is produced by divalent anti-Mo5 immunoglobulin [F(ab')2 but not F(ab)]. After down modulation, Mo5 is reexpressed by monocytes within 48 hours. Mo5 is therefore a human myelomonocytic differentiation antigen whose expression is modulated up or down depending on the nature of extracellular stimuli. PMID- 2579693 TI - Lactate transport in rat aorta. AB - Ouabain (10 mM) and gramicidin (5 micrograms/ml) do not inhibit lactate uptake by rat aortic rings. This supports the interpretation that a Na+ gradient is not involved in lactate transport. Dinitrophenol (25 microM) fails to inhibit lactate uptake, suggesting that oxidative metabolism is not required for lactate uptake. DIDS (4,4'-diisothiocyano-2,2'-stilbenedisulfonate), quercetin, and alpha-cyano-4 hydroxy-cinnamate-agents that have been reported to inhibit lactate transport in other cell types-were ineffective in inhibiting lactate transport in rat aortic rings. Inhibition of lactate uptake by glyceraldehyde is not stereospecific, does not involve inhibition of glucose phosphorylation, and does not appear to involve interaction with membrane sulfhydryls. PCMBS (p-chloromercuribenzenesulfonate) does not markedly inhibit the initial rate of lactate uptake, but diminishes the lactate space at later times. Pyruvate, phenylpyruvate, and thiolactate inhibit lactate uptake, but propionate and glycolate are poor inhibitors. PMID- 2579694 TI - Comparison of nuclear proteins from DMBA-induced mammary tumors and lactating mammary glands by polyacrylamide gel electrophoresis. AB - Nuclear proteins were extracted from purified nuclei of 7,12 dimethylbenz(a)anthracene(DMBA)-induced tumors and normal mammary glands of the rat by enzymatic treatment. Of the 34 bands indicated by one-dimensional polyacrylamide gel electrophoresis of nuclear proteins, 6 appeared in high concentration in tumors but were found as traces or undetectable in normal glands; 6 others were clearly shown in the latter but were not detectable or greatly reduced in the former. Two-dimensional electrophoresis identified about 130 and 92 non-histone proteins in normal mammary and tumor cell nuclei respectively. Marked differences in spot density were noted especially in spots (M.W. X 10(-3)/pI) 100/5.7 and 200/5.5 of tumors and 28/7.1, 32/5.4, 36/5.4, 38/6.9, and 68/6.0 of normal tissue. The relationship between these nuclear proteins and the development of mammary tumors is also discussed. PMID- 2579695 TI - Competition of fate processes in the bioconcentration of lindane. PMID- 2579696 TI - RESCUE: an audiovisual rescue squad consortium. PMID- 2579697 TI - 5-Hydroxytryptamine release in vivo from a cytoplasmic pool: studies on the 5-HT behavioural syndrome in reserpinized rats. AB - Treatment of rats with reserpine in order to disrupt vesicular amine storage reduces 5-hydroxytryptamine (5-HT) levels throughout brain by 90-95%. Despite the drastic reduction in brain 5-HT content by reserpine, the 5-HT releasing drug p chloramphetamine (PCA) produces a behavioural syndrome in reserpine-treated rats which is not different from that observed in normal animals given PCA. Prior treatment of reserpinized rats with p-chlorophenylalanine (PCPA), the irreversible tryptophan hydroxylase inhibitor which inhibits the synthesis of new 5-HT, prevents the PCA-induced behavioural syndrome. The 5-HT receptor antagonist methergoline, blocks the PCA effect in reserpine-treated rats. Treatment of reserpinized rats with pargyline, a non-selective inhibitor of monoamine oxidase, in order to increase cerebral 5-HT levels, shifts the PCA dose-response curve for inducing the 5-HT behavioural syndrome to the left. The specific 5-HT uptake blocker, fluoxetine, protects normal and reserpine-treated rats from the 5-HT depleting effects of PCA but does not always prevent the PCA-induced 5-HT behavioural syndrome. These results indicate that PCA releases 5-HT into the synapse from a small cytoplasmic pool which is resistant to reserpine and suggest that this newly synthesized compartment of 5-HT represents the 'functional' transmitter pool. PMID- 2579698 TI - The relationship between coronary artery occlusion-induced arrhythmias and myocardial cyclic nucleotide levels in the anaesthetized rat. AB - The aims of this study were to determine whether a relationship exists between the occurrence of coronary artery occlusion-induced arrhythmias in the anaesthetized rat and the levels of cyclic AMP and cyclic GMP in both normal and ischaemic myocardium, and to assess whether such arrhythmias were modified by pretreatment with the phosphodiesterase inhibitors, quazodine and isobutyl methylxanthine (IBMX), or with the butyryl derivatives of cyclic AMP and cyclic GMP. At 5 min after coronary artery ligation (when only a few arrhythmias had occurred) both cyclic AMP and cyclic GMP levels were elevated in normal myocardium whereas in ischaemic tissue only cyclic AMP was raised. As the peak of the arrhythmic activity and after cessation of the arrhythmias, i.e. at 10 and 30 min post-ligation respectively, levels of both nucleotides had fallen in ischaemic although not in normal tissue. The severity of these occlusion-induced arrhythmias was exacerbated by pretreatment intravenously with quazodine, IBMX, dibutyryl cyclic AMP and dibutyryl cyclic GMP. Pretreatment with IBMX was also shown to elevate significantly both cyclic AMP and cyclic GMP content of left ventricular tissue before occlusion. None of the drug pretreatments markedly affected mean arterial blood pressure but heart rate was significantly increased following quazodine and IBMX administration. We conclude that in the pentobarbitone-anaesthetized rat the occurrence of occlusion-induced arrhythmias was not accompanied by a rise in cyclic nucleotide content of the ischaemic myocardium but agents which may elevate either myocardial cyclic AMP or cyclic GMP levels exacerbate such arrhythmias. PMID- 2579699 TI - Effects of verapamil on the contractions of guinea-pig tracheal muscle induced by Ca, Sr and Ba. AB - A comparison was made of contractions produced by calcium (Ca), strontium (Sr) or barium (Ba) in guinea-pig tracheal smooth muscle after the preparation had been relaxed in Ca-free medium. Most of the experiments were carried out in the presence of indomethacin (5 microM) to inhibit endogenous prostaglandin synthesis. In 40 mM K+ solution, the Ca, Sr and Ba concentrations which produced 50% of maximum tension responses were 0.07 mM, 1 mM and 2 mM, respectively. Maximum tension of a similar size was produced by either 2.4 mM Ca, 9.6 mM Sr or 9.6 mM Ba. The Ca-induced contraction in 5.9 mM K solution, which is probably due to the presence of endogenous prostaglandins, was not significantly affected by verapamil. When the external K concentration was increased to 40 mM, the Ca induced contraction became susceptible to inhibition by verapamil. Similarly, contractions induced by Sr and Ba in excess K solution were strongly suppressed by verapamil. In the presence of prostaglandin (PG) F2 alpha (1.4 microM) or carbachol (5 microM), Ca, Sr and Ba produced contractions in both the 5.9 mM K and 40 mM K solutions. Contractions produced by PGF2 alpha or carbachol in the presence of Ca were little affected by 10 microM verapamil, whereas those in the presence of Sr or Ba were strongly suppressed by verapamil in both the 5.9 and 40 mM K solutions. 4 A strong suppressant effect of verapamil on the K-induced contraction, but a weak effect on the drug-induced contraction, in the presence of Ca can be explained by assuming that verapamil blocks voltage-operated Ca channels, but not receptor-operated Ca channels. However, this theory cannot account for the effect of verapamil on drug-induced contractions in the presence of Sr or Ba. It may be that susceptibility to verapamil is determined by the relative affinity of'the divalent cations and verapamil for the Ca channels, both for voltage- and receptor-operated channels. PMID- 2579700 TI - GABAB receptor modulation of adenylate cyclase activity in rat brain slices. AB - An investigation of the effects of gamma-aminobutyric acid (GABA) and the selective GABAB receptor agonist, baclofen, on basal and stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels in slices of rat cerebral cortex has been carried out. Neither GABA nor baclofen produced any significant change in basal cyclic AMP levels. By contrast noradrenaline and forskolin both produced dose-dependent increases in cellular cyclic AMP accumulation. GABA (in the presence of nipecotic acid) and baclofen both potentiated the maximal response to noradrenaline with baclofen (100 microM) increasing the level of cyclic AMP produced by noradrenaline (100 microM) by 133%. GABA (0.3-100 microM) was rather less effective than baclofen, increasing the response to noradrenaline by 70% at 100 microM. (-)-Baclofen was the active isomer with (+)-baclofen failing to potentiate noradrenaline responses. Bicuculline-methobromide (100 microM) failed to block the action of either GABA or baclofen. The enhancement of adrenoceptor stimulated cyclic AMP accumulation persisted in the presence of a phosphodiesterase inhibitor (1 mM 3-isobutyl-1-methylxanthine) and also in Ca2+ free solution. When forskolin was used to stimulate adenylate cyclase, the effect of baclofen was to inhibit the rise in cyclic AMP levels. Thus (-)-baclofen (100 microM) shifted the dose-response curve to forskolin to the right 5 fold in an apparently parallel fashion. The effect was again stereospecific for the (-) isomer of baclofen. When GABA uptake was reduced using low sodium (40 mM) incubation medium, GABA also attenuated the rise in cyclic AMP induced by 10 microM forskolin. GABA produced little effect in normal Krebs solution. PMID- 2579703 TI - A comparison of normal and pathological synovial fluid. AB - Synovial fluid from 16 normal subjects was compared with that from 149 patients with a variety of rheumatic disorders. Normal fluid had fewer cells and a lower content of beta-glucuronidase than osteoarthritic samples. Particles, including occasional birefringent crystals, were seen in normal fluids as well as pathological samples. Alizarin red staining particles (presumed to contain apatite) were seen in all diagnostic groups; their numbers showed some correlation with radiological calcification in and around the joints and with a hypertrophic subchondral bone response. Lactate levels were highest in septic arthritis. No assay showed disease specificity. PMID- 2579701 TI - gamma-Aminobutyric acid- and piperazine-activated single-channel currents from Ascaris suum body muscle. AB - gamma-Aminobutyric acid (GABA)- and piperazine-activated single-channel currents were recorded from the bag region of the somatic muscle of the nematode parasite Ascaris suum. Cell-attached and outside-out patch-clamp techniques were used. Clean membranes were routinely prepared using collagenase. GABA (concentrations greater than 1 microM) or piperazine (concentrations greater than 200 microM) applied to the extracellular surface of the patches brought about the opening of channels producing rectangular shaped current pulses of varying duration but essentially constant amplitude. The I/V relationships of the single-channel currents for both agonists were linear and had conductances in the region of 22 pS (in symmetrical 170 mM Cl-). The reversal potential was near 0 mV when Cl- was equally distributed on both sides of the membrane. Occasionally two subconductance states were seen. The mainstate single-channel permeability was estimated to be 4 X 10(-14) cm3 s-1. At low concentrations of GABA (3-4 microM), the effective mean channel open time was in the region of 32 ms (-75 mV, 22 degrees C, cell-attached patches). At low concentrations of piperazine (500 microM) the effective mean open channel lifetime was shorter, in the region of 14 ms (-75 mV, 22 degrees C cell-attached patches). For each agonist the channel open lifetime distributions were best described by the sum of two exponentials suggesting two open mainstates. Channel openings occurred as single events and in bursts with brief closed periods within bursts. The channel closed time histograms at these concentrations were best described by the sum of up to three exponentials, suggesting the presence of three closed states. Channel open times showed no appreciable voltage sensitivity. Before desensitization, increases in agonist concentration produced an increase in the probability of the channel being open. The increased probability was associated with an increase in the frequency of channel opening, an increase in the effective mean channel open time, an increase in burst duration, an increase in the number of openings per burst, together with a reduction in the proportion of brief openings. Desensitization was seen as a decline in the probability of the channel being opened during prolonged applications of agonist. It was associated with the appearance of very long (seconds) closed periods. The distributions of the closed channel times were then best described by up to four exponentials. PMID- 2579702 TI - Differential antagonism by Bay k 8644, a dihydropyridine calcium agonist, of the negative inotropic effects of nifedipine, verapamil, diltiazem and manganese ions in canine ventricular muscle. AB - Antagonism between either the dihydropyridine calcium agonist, Bay k 8644, or high external Ca2+ and the calcium antagonists, nifedipine, verapamil and diltiazem, and Mn2+ was investigated in canine isolated ventricular trabeculae. Bay k 8644 (10(-7)-10(-5)M) produced a slowly developing increase in developed tension which reached a maximum at 10(-6)M. A small decrease in the positive inotropic effect of Bay k 8644 at 10(-5)M was probably due to the negative inotropic effect of the solvent, 0.5% ethanol. Bay k 8644 (10(-7)-10(-5)M) produced a rightward parallel shift of the concentration-response curves for the negative inotropic effects of nifedipine (10(-8)-10(-5)M) and verapamil (10(-7)-3 X 10(-5)M). The slopes of the Schild plots were -0.92 for nifedipine (pA2 value = 6.58) and -0.48 for verapamil. Bay k 8644 (10(-6) and 10(-5)M) produced only a slight rightward shift of the concentration-response curves for the negative inotropic effect of diltiazem (10(-7)-3 X 10(-5)M) and did not affect the negative inotropic effect of Mn2+ (10(-4)-10(-2)M). Addition of 2.5 X 10(-3)M Ca2+ (5.05 X 10(-3)M Ca2+) to the medium produced a greater maximum positive inotropic effect than Bay k 8644. The concentration-response curves for the negative inotropic effects of nifedipine, verapamil and diltiazem obtained under these conditions were not essentially different from those under control conditions (2.55 X 10(-3)M Ca2+). 6 These results indicate that Bay k 8644, while producing a positive inotropic effect, antagonizes the negative inotropic effect of nifedipine by competing with the latter for the same site closely associated with the calcium channel. In contrast, Bay k 8644 antagonizes the negative inotropic effects of verapamil and diltiazem by interfering allosterically with the binding of these calcium antagonists to their sites of action. Bay k 8644 does not antagonize the negative inotropic effect of Mn2+. No pharmacological antagonism was observed between the three organic calcium antagonists and high external Ca2+_ PMID- 2579704 TI - Intraperitoneal low-pressure suction drainage following splenectomy. AB - A consecutive series of 282 patients undergoing splenectomy on one surgical unit has been studied to ascertain the incidence of postoperative subphrenic abscess. Only two atypical subphrenic abscesses occurred (0.17 per cent), a rate of abscess formation much lower than that reported in other series. We believe that the use of low-pressure closed suction drainage to the splenic bed accounts for this low rate. PMID- 2579705 TI - The effects of slowed speech on auditory comprehension in aphasia. AB - The present study investigates the effects of slowed speech on auditory comprehension in aphasia. Specifically, an attempt was made to isolate the effects of added time on comprehension at the language processing stages of auditory perception, by increasing the duration of the vowel segments in each word; word recognition and semantic analysis, by adding silences between words; and syntactic analysis, by adding silences at constituent phrase boundaries. Sentences were also read at a slow rate to see the effects of naturally slowed speech on sentence comprehension. Test sentences consisted of simple active and passive declarative sentences, and complex sentences with embedded medial and final relative clauses. Sentences were either semantically reversible or nonreversible. Thirty-four aphasic patients who varied in both severity and type of aphasia were tested on a picture verification task. Results indicated that slowing facilitated language comprehension significantly only in the syntactic condition. Neither syntactic complexity nor semantic reversibility interacted with slowed speech to facilitate auditory language comprehension. Further, it was only the Wernicke's aphasics who showed significant improvement with time added at constituent boundaries. These results suggest that time alone does not facilitate language comprehension in aphasia, but that rather it is the interaction of time with syntactic processing which improves comprehension. PMID- 2579706 TI - Evidence that substance P and somatostatin transmit separate information related to pain in the spinal dorsal horn. AB - Effects of various types of natural skin stimuli on the in situ release of immunoreactive substance P and somatostatin from the rabbit dorsal horn were examined. Noxious mechanical or thermal stimuli specifically increased the release of immunoreactive substance P or somatostatin, respectively. Innocuous stimuli did not affect the release of these peptides. These results suggest that the nociceptive mechanical or thermal primary afferents contain substance P or somatostatin, respectively. PMID- 2579707 TI - Evidence for the existence of substance P-like immunoreactive neurons in the human cerebral cortex: an immunohistochemical analysis. AB - Cellular localization of substance P-like immunoreactive (SP-IR) structures in the pre- and postcentral gyri of the human cerebral cortex was examined by indirect immunofluorescence. SP-IR was localized mostly in bipolar and partly in multipolar cells in layers II and IV. SP-IR fibers were also noted in these gyri, especially in layers II and IV. PMID- 2579708 TI - Dendritic spines: role of active membrane in modulating synaptic efficacy. AB - Dendritic spines have been increasingly implicated as sites for neuronal plasticity. Earlier-theoretical studies of dendritic-spine function have assumed passive membrane, and have consequently predicted that postsynaptic potentials in the dendrite are attenuated when the synapse is located on the spine head rather than on the dendritic shaft. Our studies show that active membrane in the spine head (e.g. voltage-dependent Na+ or Ca2+ channels) can produce amplification rather than attenuation of the postsynaptic potential. The presence and amount of amplification depend on the density of active channels and on the spine-neck resistance. For a given type of spine head, there is an optimal spine-neck resistance; a given change in neck resistance can therefore either increase or decrease the amplitude of postsynaptic potentials. These results support the idea that spines mediate synaptic plasticity and suggest a variety of modulatory mechanisms. PMID- 2579709 TI - Effects of anticonvulsants on spontaneous epileptiform activity which develops in the absence of chemical synaptic transmission in hippocampal slices. AB - Spontaneous epileptiform activity (SEA) develops in area CA1 of hippocampal slices, when the Ca2+ concentration in the perfusate is lowered to 0.2 mM, at which level evoked chemical synaptic transmission is blocked. We investigated the effects of different anticonvulsants on this autonomous activity, in order to determine whether the antiepileptic effect can be ascribed to an influence on neuronal excitability. Carbamazepine was the most effective to block SEA at concentrations of 1-15 microM. Phenobarbital and phenytoin depressed SEA at concentrations of 25 microM. Valproate was effective at concentrations of 2-5 mM. Midazolam, a water-soluble benzo-diazepine agonist and the N-methyl-D-aspartate antagonists, DL-alpha-aminoadipic acid and 2-amino-7-phosphonoheptanoic acid were ineffective in blocking SEA suggesting that they exert their antiepileptic action by interference with synaptic mechanisms. PMID- 2579710 TI - Myelin basic protein has lectin-like properties. AB - Myelin basic proteins (MBP) obtained from bovine, guinea pig and human nervous tissues exhibited hemagglutinating activity for erythrocytes of several animal species. The activity to each erythrocyte was actually equal among the 3 MBPs. With bovine MBP and chicken erythrocytes, the hemagglutinating activity did not require divalent cations and it was resistant to denaturing conditions such as urea treatment or heating of the protein. The activity was specifically inhibited by antisera to MBP, allowing hemagglutination inhibition assay to be a useful method for estimating antibody titers for MBP. Various sugars and glycoproteins were tested for their ability to inhibit MBP-mediated hemagglutination. Among mono- and disaccharides, only D-galactose and D-galactosamine exhibited an inhibitory effect at high concentration. Beta-Galactopyranoside was found to be 8 fold effective compared to alpha-anomer. Among glycoproteins, glycophorin and kappa-casein were potent inhibitors, while fetuin, ovalbumin and ovomucoid were ineffective. Either of the former two glycoproteins was observed to form a clear precipitin band with MBP in Ouchterlony double diffusion. Possible interaction of MBP with certain saccharide receptor was briefly discussed. PMID- 2579711 TI - Two subtypes of sodium channel with tetrodotoxin sensitivity and insensitivity detected in denervated mammalian skeletal muscle. AB - The action potential (AP) in most nerve and muscle preparations depends upon nanomolar concentrations of the neurotoxins saxitoxin (STX) and tetrodotoxin (TTX). In some excitable tissues lacking mature innervation, a toxin-resistant AP has been described by electrophysiological results. However, multiple attempts to detect corresponding toxin-resistant Na channels with radiolabelled STX and TTX have been unsuccessful. We report here the detection of Na channels with low affinity binding of STX and TTX, accounting for 50-60% of the Na channels in rat hindlimb muscle 4-5 days after denervation. PMID- 2579712 TI - Beneficial effect of gamma-endorphin-type peptides in anaphylactic shock. AB - gamma-Endorphin-type peptides (i.e. gamma-endorphin, des-tyr'-gamma-endorphin [DT gamma E]) result from the processing of the opioid peptide, beta-endorphin. Previous studies have implicated the involvement of beta-endorphin in various types of shock, including anaphylactic shock. In the present experiments the intracerebroventricular (i.c.v.) administration of gamma-endorphin (10 micrograms) or DT gamma E (3.3-10 micrograms) significantly improved survival in anaphylactic shock in mice. Moreover, DT gamma E (10 micrograms) reversed the effect of i.c.v. beta-endorphin (3.3 micrograms) to exacerbate shock. A similar dose of DT gamma E was ineffective in antagonizing beta-endorphin-induced analgesia. The anti-anaphylactic action of DT gamma E as well as its effect to block the pro-anaphylactic action of beta-endorphin were prevented by pretreatment with the sympathetic ganglionic blocker, chlorisondamine chloride. The results suggest that gamma-endorphin-type peptides may act in the central nervous system (CNS) to physiologically oppose the autonomic pathophysiologic influences of beta-endorphin. PMID- 2579713 TI - Substance P in subdivisions of the sciatic nerve, and in red and white skeletal muscles. AB - Substance P (SP) has been determined by radioimmunoassay in the sciatic nerve and its fibular, tibial and sural branches; and in a red, slow-twitch and a white, fast-twitch muscle supplied by the sciatic nerve. The mixed sciatic nerve contained 25 ng SP per g tissue wet wt., while the sural branch, which is supplying mainly skin, and thus is rich in sensory fibres, had a significantly higher content (49 ng/g). The mixed fibular and tibial branches contained approximately the same amount as the sciatic nerve proper. SP was also found in the skeletal muscles. The red m. soleus had a significantly higher content (0.61 ng/g) than the white m. extensor digitorum longus (0.22 ng/g). A dorsal root lesion which leads to degeneration of sensory fibres, reduced the SP level more than 90% both in nerves and muscles. Ventral root section, which leads to degeneration of somato-motor fibres and terminals, had, on the other hand, no effect. We conclude that sensory neurons are the only source of importance for SP in the sciatic nerve and in skeletal muscles. Based on the above findings, the possibility that SP may function as a mediator of an axon reflex in skeletal muscle is discussed. PMID- 2579714 TI - Alzheimer's disease: errors in gene expression. PMID- 2579716 TI - Reanalysis of the RTOG study of the palliation of symptomatic osseous metastasis. AB - This is a reanalysis of the data from the Radiation Therapy Oncology Group (RTOG) study of the palliation of metastasis to bone. The RTOG multicenter clinical trial studied pain relief in 759 patients randomly assigned to a variety of dose fractionation schedules: 270 cGy X 15 fractions, 300 X 10, 300 X 5,400 X 5, and 500 X 5. The multivariate statistical technique of logistic regression was used. The results differed from a previous report in that number of fractions was statistically significantly related to complete combined relief (that is, absence of pain and cessation of the use of narcotics). Also, the time dose factor (TDF) isoeffect conversion did not accurately predict tumor response. The conclusion is that protracted dose-fractionation schedules are more effective than short course schedules. PMID- 2579717 TI - Hepatic tumors in Saudi Arabia. A practical approach to diagnosis. AB - All cases of liver tumor referred to the King Faisal Specialist Hospital and Research Centre in Saudi Arabia during 2.5 years were reviewed. Hepatocellular carcinoma, 104 cases, was considerably more common than metastatic carcinoma with unknown primary, 15 cases. Lymphoma presenting as liver tumor occurred in three cases and there were no cases of cholangiocarcinoma. There were only two cases of benign tumor, both hemangioma. Hepatocellular carcinoma was characterized by a male predominance of 6:1, positive hepatitis B surface antigen in 60%, presentation with an enlarged, hard liver in over 90%, a systolic-diastolic bruit over the mass in 45%, a single highly echogenic lesion in the right lobe on ultrasound in 80%, and rapid progression. The serum AST (aspartate aminotransferase, serumglutamic oxalacetic transaminase [SGOT]) was abnormal in 97% and was higher than the alanine aminotransferase (ALT) in 93% of cases compared with 17% in 100 consecutive cases of chronic active hepatitis. Sixty-six percent of patients with hepatocellular carcinoma had serum AFP greater than 200 ng/ml. Excluding five cases of germ cell tumor (none involving the liver), and pregnant patients, serum AFP was less than 200 ng/ml in all other patients in whom it was measured between 1979 and 1981. A practical approach to the diagnosis of hepatocellular carcinoma is outlined. Biopsy does not appear to be indicated in many cases of advanced hepatocellular carcinoma. PMID- 2579718 TI - Distinction of mesothelioma from adenocarcinoma. An immunohistochemical approach. AB - The authors investigated the expression of keratin, carcinoembryonic antigen (CEA), and an epithelial marker derived from milk fat globule membranes in 12 mesotheliomas and 100 diverse adenocarcinomas with immunohistochemical methods. The authors employed a monoclonal antibody to keratin designated as AE1, as well as the following commercially available antisera: rabbit anti-whole human keratin, rabbit anti-CEA, and a monoclonal antibody to an epithelial factor designated as MFG-2. Expression of keratin was found in all the mesotheliomas and adenocarcinomas with antibody AE1 as well as with the rabbit antiserum; CEA was detectable in 65% of the adenocarcinomas but two mesotheliomas also reacted weakly. With antibody MFG-2, positive results were obtained in 85% of the adenocarcinomas and in none of the mesotheliomas. All of 64 (100%) breast-, lung- and ovary-derived adenocarcinomas immunostained positively with antibody MFG-2. This is of particular significance because pulmonary and ovarian adenocarcinoma frequently may be indistinguishable clinically and histologically from epithelial mesothelioma. The authors conclude that antikeratin antibodies are not useful in the distinction of adenocarcinoma from mesothelioma. Because of its greater sensitivity and specificity, MFG-2 is superior to CEA in this differential diagnosis. PMID- 2579719 TI - Ultrastructural morphometry and secretory behavior of acinic cell carcinoma. AB - Cells from three parotid acinic cell carcinomas were compared stereologically with normal parotid acinar cells. The morphometric studies revealed that the granular volume density was increased in the tumor cells. The cells contained more granules, but the mean granule diameter was considerably less, compared with normal controls. On the other hand, no difference in cell volume or nuclear volume density could be found. Although morphologically similar to normal acinar cells, the tumor cells had a much lower content of amylase. However, in a batch incubated system, amylase secretion could be elicited with noradrenaline from the tumor cells. Furthermore, noradrenaline stimulation increases tumor tissue cyclic AMP content dramatically. The current study demonstrated the similarity between normal acinar cells and acinic cell tumor cells: the latter respond to physiologic secretion stimuli with an increased tissue level of cyclic AMP accompanied by amylase release. PMID- 2579715 TI - Urticaria and angioedema. PMID- 2579721 TI - Lung metastasis of malignant epithelioid hemangioendothelioma mimicking a primary intravascular bronchioalveolar tumor. A histologic, ultrastructural, and immunohistochemical study. AB - A 40-year-old woman presented with multiple nodules in both lungs and a small tumoral mass at the level of the left brachial artery. A pathologic diagnosis of pulmonary intravascular bronchioloalveolar tumor (IVBAT) and epithelioid hemangioendothelioma of the limb was established. Morphologic and immunohistochemical studies highly suggest that both tumors are manifestations of the same neoplastic process. In this case a metastatic nature of the IVBAT is suggested. The diagnosis of pulmonary IVBAT should be followed by a search for sclerosing vascular tumors elsewhere. Finally, the results substantiate the vascular origin of the IVBAT. PMID- 2579720 TI - T-helper cell lymphoma involving the lymph nodes and skin. A clinical, morphologic, and immunohistochemical analysis of five cases. AB - The clinical, morphologic, and immunohistochemical features of 5 cases of peripheral T-cell lymphoma with lymph node and skin involvement are reported. All patients were male and presented with generalized lymphadenopathy and skin lesions. Lymph node biopsy specimens showed a diffusely growing, pleomorphic, atypical lymphoid infiltrate composed of markedly irregular small and large cells. The stroma consisted of plasma cells, eosinophils, epithelioid histiocytes, and an increased number of small blood vessels. A similar neoplastic infiltrate was observed in the cutaneous nodules that developed in three patients. Immunohistochemistry on frozen tissue sections of lymph nodes using a broad panel of monoclonal antibodies revealed that the neoplastic cells were reactive with anti-T-cell antibodies, the majority of them belonging to the helper/inducer T-cell subset. Stromal plasma cells contained polyclonal immunoglobulins. It is concluded that the malignant lymphoma of peripheral helper/inducer T-cell origin observed in these five patients represents a variant of a mixed, blastic/cell T-cell lymphoma, characterized by a peculiar stromal component and skin involvement. PMID- 2579722 TI - The use of BELD combination chemotherapy (bleomycin, vindesine, CCNU, and DTIC) in advanced malignant melanoma. AB - Twenty-one patients with Stage III malignant melanoma have been treated with a 5 day quadruple chemotherapy regime (BELD) comprising bleomycin 15 mg subcutaneously on days 1 and 4, vindesine (Eldesine) 3 mg/m2 intravenously on days 1 and 5, CCNU (lomusine) 80 mg/m2 orally on day 1, and DTIC 200 mg/m2 intravenously on days 1 through 5. Twenty patients were evaluated after two cycles. Three (15%) are in complete remission 12, 16, and 53 weeks after therapy, respectively, and six (30%) experienced worthwhile partial remissions. This combined response rate of 45% is considerably better than that seen in single- or dual-agent chemotherapy. Toxicity was acceptable, and several patients received their therapy on an outpatient (ambulatory) basis. The one nonevaluable patient had radiotherapy for an isolated spinal metastasis and two courses of BELD. She is well and pain- and disease-free 56 weeks later. The median survival for all treated patients is 43 weeks, and the median follow-up time is now 63 weeks. PMID- 2579723 TI - Accelerated treatment. AB - In the first third of this century, the prevailing concept was that malignant cells had a brief period of sensitivity and radiation treatments were ideally given in overall times of 2 weeks or less. Following the Second World War, routine treatment times were extended to 5 to 8 weeks to avoid severe acute normal tissue reactions and achieve higher tumor doses. In reaction to these prolonged overall times, a series of large-fraction, shortened-overall-time clinical experiments were attempted, with disastrous normal tissue effects and poor tumor control. More recently, attempts to accelerate treatment have been accomplished by utilizing multiple fractions per day or semicontinuous irradiation. Unfortunately, the majority of these attempts have been forced by the occurrence of unacceptable normal tissue reactions to significantly reduce total dose or introduce lengthy splits in treatment. These results suggest that in our current state of knowledge accelerated schedules be reserved for use in the treatment of rapidly proliferating neoplasms or for palliation. PMID- 2579724 TI - Combined modality treatment of head and neck cancer with cisplatin, bleomycin, methotrexate-leucovorin chemotherapy. AB - The multidisciplinary treatment results of 114 patients with advanced, untreated Stage III and IV squamous cell carcinoma of the head and neck region are reported. Induction chemotherapy with two cycles of cisplatin 20 mg/m2/day intravenous bolus days 1 through 5, bleomycin 10 mg/m2/day as a continuous infusion days 3 through 7, and methotrexate 200 mg/m2 intravenous bolus on days 15 and 22 with leucovorin rescue was utilized before definitive surgery and/or radiation therapy. The total response rate was 78% with 30 (26%) patients achieving complete response and 59 (52%) patients achieving partial response. Patient age, performance status, histologic grade of tumor, and tumor site did not predict response to chemotherapy. Induction chemotherapy was well tolerated with myelosuppression and nephrotoxicity being dose-limiting in a few patients. The toxicity of subsequent local treatment with surgery and/or radiation is reported with an analysis of local treatment failures. A strong correlation was noted between local control of tumor and postchemotherapy tumor size before local treatment. PMID- 2579725 TI - The role of radiation therapy in the management of the non-Hodgkin's lymphomas. AB - Radiation therapy has a broad range of applications in the management of patients with non-Hodgkin's lymphoma. It has curative potential for patients with Stage I to II low-grade lymphoma (small lymphocytic, follicular small cleaved, and follicular mixed) and has substantial palliative efficacy in patients with more advanced stage low-grade lymphoma. Low-dose whole-body irradiation may be used as palliative therapy even in patients with bone marrow involvement by these lymphomas. In the management of the large cell lymphomas (diffuse large cell, diffuse mixed, and immunoblastic), radiation alone has curative potential in only the most favorable early-stage presentations. However, since radiation can achieve significant responses in these tumors, it should be considered for inclusion in combined-modality programs. Reports that have appeared in the literature as well as results of treatment at Stanford that bear upon these issues are reviewed. PMID- 2579726 TI - Systemic hemibody irradiation for overt and occult metastases. AB - Hemibody irradiation was initially employed as a palliative technique to treat diffuse metastatic disease in one session as opposed to multiple fields over an extended period. It provides a radiation treatment for disseminated cancer and therefore has been termed "systemic" therapy. Since it is possible to treat both halves of the body sequentially, it allows radiation treatment to the whole body in larger doses than could be accomplished with total-body irradiation. Because of the success in terms of dramatic rapid pain relief and the objective response on metastatic disease, it has been explored in the treatment of occult disease and as consolidation therapy in patients with tumors that have responded to chemotherapy. When hemibody irradiation is combined with chemotherapy, responses have been shown in metastases for several primaries, particularly small cell carcinoma, which is perhaps the most encouraging, and supports further research in the treatment of micrometastatic disease for this tumor type. As the technique moves from its current research phase into more general clinical use, radiation oncologists should become more familiar with the treatment, and the hospitalization originally required may be able to be avoided. An intensive premedication program has been developed to facilitate this. Innovative approaches using radiosensitizers, radioprotectors, hyperthermia, and hyperfractionation are ideas that are starting to be tested and will be further explored in the near future. PMID- 2579727 TI - Controversies in the management of testicular seminoma. AB - The 5-year cause specific actuarial survival rate for 178 patients treated for testicular seminoma at The Princess Margaret Hospital 1977 to 1981 is 97%. Controversies exist over how to optimally use and integrate chemotherapy (CT) and radiation therapy (RT) to minimize morbidity and achieve these high cure rates. These are as follows: "surveillance only" for Stage I, the necessity of prophylactic mediastinal RT (PMI) for Stage IIA, initial RT versus CT for Stage IIB, optimal therapy for Stages III and IV, and the significance of elevated serum tumour markers. In Stage I, relapse after abdominopelvic RT (2500 cGy in 20 fractions) occurred in 2 of 150 patients (1.3%). Without routine RT relapse rates are unknown. Only 1/370 Stage IIA patients in the literature treated with infradiaphragmatic RT without PMI developed uncontrolled mediastinal disease. Prophylactic mediastinal RT confers a possible survival benefit of only 0.2% and cannot be recommended. Stage IIB is rare (only 4% of 178 patients). Initial CT produces complete responses in approximately 80% of patients, but its curative potential is unknown therefore consolidation RT or surgery is often given. Initial subdiaphragmatic RT followed by CT for relapse cures at least 85% of patients (5/5 marker negative) and spares 50% of unnecessary CT. Sequential therapy minimizes potential treatment morbidity without compromising cure. Initial CT is recommended for Stages III and IV. The literature survival after RT is only 36% (136/375). The role of consolidation RT is unknown. Optimal management of seminoma implies integration of RT and CT to decrease morbidity and still maintain high cure rates. PMID- 2579728 TI - The activity of nucleolar organizer regions of human bone marrow cells studied with silver staining. I. Chronic myelocytic leukemia. AB - The activity of nucleolar organizer regions (NORs) in chromosomes and interphase nuclei of bone marrow (BM) cells from 21 patients with chronic myelocytic leukemia (CML), including seven patients at the time of blastic crisis (BC), has been studied with silver nitrate staining. The average numbers of Ag-NOR per metaphase in PHA-stimulated peripheral blood lymphocytes from patients with CML and normal individuals were 7.1 +/- 0.3 and 7.4 +/- 0.1, respectively, indicating no statistical difference between them. Those in BM cells from patients with CML, as in the normal donors, were more heterogeneous compared to PHA-stimulated lymphocytes, and most of the metaphases (up to 67%) did not contain silver stained NORs. The average number of Ag-positive NORs in BM mitoses from untreated patients in the chronic phases of CML and from those in the BC were similar (4.9 +/- 0.3 and 4.8 +/- 0.4, respectively). As for NORs of the Ph chromosome, they were Ag-positive in the majority of patients, including 9 of 14 in the chronic phase and 3 of 7 in the BC. This article contains some data in support of the authors' previous assumption regarding the correlation between BM Ag-NOR patterns and the degree of maturity of the cells tested in mitosis. PMID- 2579729 TI - Lack of specific inhibition of DNA repair in WI-38 human diploid fibroblasts by sodium saccharin. AB - The ability of sodium saccharin (NaS) to inhibit the repair of DNA damaged by UV irradiation was examined in cultured WI-38 human diploid fibroblasts. Cesium chloride density gradient ultracentrifugation was used to measure DNA repair and DNA replication. NaS (10-10,000 micrograms/ml) did not specifically inhibit UV light-induced DNA repair. At doses of NaS (1785 and 10,000 micrograms/ml) that caused a 62-67% inhibition of semiconservative DNA replication, there was little or no inhibition of DNA repair synthesis. In cell cultures not exposed to UV irradiation, NaS failed to induce DNA repair. RNA synthesis and protein synthesis were unaffected by NaS at all doses tested. The inhibition of semiconservative DNA replication at higher doses of NaS may be a manifestation of cytotoxicity. In contrast to results with NaS, WI-38 cells were very sensitive to DNA repair inhibition by the well-studied inhibitor quinacrine-HCl. These results do not support mechanisms of saccharin-induced tumorigenesis involving either direct induction of DNA damage or inhibition of the repair of DNA damage caused by other agents. PMID- 2579730 TI - Host-mediated therapeutic effects produced by appropriately timed administration of bleomycin on a rat fibrosarcoma. AB - The timing of bleomycin (BLM) administration after KMT-17 tumor inoculation was found to be important for optimizing its therapeutic effect on tumor-bearing rats. A remarkable therapeutic effect was observed when BLM (5 mg/kg/day) was administered i.p. for 5 days from the eighth day after tumor inoculation (Day 8 to Day 12) rather than when BLM was administered i.p. for 5 days during the days immediately following tumor inoculation (Day 1 and Day 5) (cured rats/treated rats: 10/21 and 2/16, respectively). By means of a Winn assay, stronger tumor neutralizing activities were observed in spleen cells from BLM (Day 8 to Day 12) treated tumor-bearing rats than were observed in spleen cells from BLM (Day 1 to Day 5)-treated tumor-bearing rats (% Inhibition: 70.9 and 49.3%, respectively). These therapeutic effects were thus found to be consistent with the antitumor immunity against KMT-17. The enhanced tumor-neutralizing activities of spleen cells from BLM-treated tumor-bearing rats were suppressed by adding spleen cells from nontreated tumor-bearing rats. In cell transfer experiments, an antitumor transplantation resistance in rats immunized with irradiated KMT-17 cells was abrogated by an adoptive transfer of spleen cells from untreated tumor-bearing rats or BLM (Day 1 to Day 5)-treated tumor-bearing rats but not from BLM (Day 8 to Day 12)-treated tumor-bearing rats. These results suggest that, when BLM is administered during a late stage of tumor growth, it is effective in eliminating suppressor cells and that this leads to an improvement in the therapeutic effects of the drug. PMID- 2579731 TI - Depression of the hepatic cytochrome P-450 monooxygenase system by treatment of mice with the antineoplastic agent 5-azacytidine. AB - The effects of 5-azacytidine (5-AC) administration on the hepatic cytochrome P 450 systems of mice were studied. A single i.p. dose of 5-AC (25 mg/kg) to male Swiss-Webster mice caused about a 50% depression of microsomal cytochromes P-450 and b5 and of ethylmorphine N-demethylase and ethoxycoumarin O-deethylase activities. Depression was greatest 24 h after treatment; by 48 to 72 h, cytochromes and drug metabolism had returned to near control values. Reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity was also depressed by 5-AC, whereas reduced nicotinamide adenine dinucleotide cytochrome c reductase was not. Incubation of 5-AC with microsomes produced no effect on drug metabolism. The prolongation of hexobarbital sleeping time by 5-AC showed that drug metabolism is also impaired by 5-AC in vivo. These studies may have important clinical implications when certain drugs are coadministered with 5 AC. PMID- 2579732 TI - Reexpression of fetal characters in simian virus 40-transformed human keratinocytes. AB - Normal human keratinocytes are able to stratify, form cornified squames, and terminally differentiate in tissue culture. These properties are frequently impaired by malignant transformation. In the present paper, we show that, in addition, transformation by SV40 results in the coordinate reexpression of a whole set of fetal characters. Moreover, a comparison of two SV40-transformed human keratinocyte cell lines, one still showing a certain degree of stratification and terminal differentiation (HE-SV) and the other almost completely unable to differentiate (SVK14), suggests that the impairment of differentiation and the intensity of reexpression of fetal markers are correlated. Particularly, a set of three keratin polypeptides, absent in adult stratified epithelia but normally found in the nonstratified fetal epidermis, is present in much larger amounts in SVK14 cells than in HE-SV cells. On the other hand, the inability of SVK14 cells, in contrast to HE-SV cells, to form cornified envelopes seems to be due to the inability of those cells to accumulate involucrin. PMID- 2579733 TI - Characterization of dihydrofolate reductase-related DNA and RNA from human KB cell subclones containing different amounts of enzyme. AB - The present study was aimed to characterize dihydrofolate reductase (DHFR) related DNA and RNA in a series of human KB cell sublines and to further understand the mechanisms of DHFR regulation. We used two probes, one which could recognize the 5' flanking sequence (p5') of the human DHFR gene and one derived from mouse complementary DNA (pDHFR 26) which contains the coding sequence for DHFR, to identify the DHFR-related DNA and RNA. Our results revealed no major differences in DNA gene structure as the copy number increases. The recognizable fragments of DHFR gene were similar including the 5' flanking sequence upstream from the first exon. We observed that all DHFR mRNA species identified were present in the subclones. The content of cytoplasmic DHFR mRNA does not always correlate with the relative gene copy number in these cell lines. Furthermore, we were able to detect high-molecular-weight RNA related to DHFR which might be the precursors of the DHFR mRNAs. Finally, using different RNA extraction procedures, we observed that different patterns of cytoplasmic DHFR mRNA can be obtained, which is probably due to differential breakdown of RNA species during extraction procedures. PMID- 2579734 TI - Detection of messenger RNAs of alpha-fetoprotein and albumin in a human hepatoma cell line by in situ hybridization. AB - Detection of RNA transcripts within individual cells by in situ hybridization provides a powerful means for identifying specific cell types actively transcribing specific genes. We have applied this technique in order to analyze expression of the alpha-fetoprotein and albumin genes in a human hepatoma cell line, HuH-7. Using either 3H- or 35S-labeled human alpha-fetoprotein complementary DNA clone as a probe, we found that essentially all HuH-7 cells contained alpha-fetoprotein mRNA, although in various amounts. This correlated well with the presence of alpha-fetoprotein in all cells as detected by the peroxidase-antiperoxidase immunoenzyme method. The intracellular concentration of albumin, on the other hand, was below the level of detection by the peroxidase antiperoxidase method. Consistent with this observation, we could not detect albumin mRNA with 3H-labeled albumin complementary DNA probes. However, the use of 35S-labeled probes having higher specific activities and higher efficiency of grain development resulted in the detection of albumin mRNA in a small percentage of HuH-7 cells. A variety of parameters involved in the in situ hybridization technique was examined to establish conditions suitable for demonstrating the presence of high- and low-copy numbers of mRNA in various cell and tissue preparations. PMID- 2579735 TI - Two-dimensional electrophoretic analysis of human prostatic fluid proteins. AB - The heterogeneous mixture of proteins present in expressed prostatic fluid from forty-nine men over 25 years old was analyzed on two-dimensional electrophoretic gels stained with silver. Samples were collected from men diagnosed with chronic prostatitis, urinary tract infection, benign prostatic hypertrophy (BPH), and prostatic carcinoma. Reference patterns were developed for all proteins observed in electrophoretograms. Over 1000 distinct proteins are contained in the comprehensive proteins pattern of prostatic fluid; however, only 18 proteins were common to all samples. No proteins unique to fluids from men with BPH or prostatic cancer were observed. Some proteins in the common proteins reference pattern of BPH patients were not seen in samples from men with prostatic cancer. Our preliminary results indicate that a series of proteins tentatively identified as variants of prostatic acid phosphatase appeared elevated in all BPH fluids but was absent or below limits of detection in samples from men with prostatic carcinoma. Our studies indicate that proteins secreted in prostatic fluid reflect physiological changes in the prostate, and certain changes may be useful indicators of malignant transformation. PMID- 2579737 TI - Fatal pneumothorax following bleomycin and other cytotoxic drugs. PMID- 2579736 TI - Effects of ricin A chain conjugates of monoclonal antibodies to human alpha fetoprotein and placental alkaline phosphatase on antigen-producing tumor cells in culture. AB - Two tumor-associated proteins, alpha-fetoprotein (AFP) and placental alkaline phosphatase (PLAP), were investigated as target proteins for antibody:cytotoxin conjugates. An AFP-producing hepatoma cell line (HepG2) and a PLAP-producing cervical carcinoma cell line (SKGIIIa) were used as target cells. Both cell lines were equally susceptible to the toxic effects of intact ricin. Immunofluorescent studies showed that AFP could be detected at the surface of the HepG2 cells in a speckled distribution, while PLAP was uniformly distributed over the surface of the SKGIIIa cells. The anti-AFP ricin A chain conjugate was not cytotoxic to either cell line at low concentrations and killed both types of cells at high concentrations. The anti-PLAP conjugate at low concentrations was 100-fold more toxic than the anti-AFP conjugate to the PLAP-producing SKGIIIa cells. At high concentrations, it also killed both types of cells. The enhanced toxicity of the anti-PLAP conjugate to the SKGIIIa cells was inhibited by an excess of unconjugated anti-PLAP but not anti-AFP, indicating that the uptake of the conjugate depends on specific cell surface binding to the antigen. The indiscriminate toxicity observed at high concentrations of either conjugate was not inhibited by unconjugated antibody, suggesting that this effect depends on conjugate uptake independent of the identity of the antigen. These results emphasize the importance of the properties of the target antigen to the cytotoxic effects of antibody conjugates as well as the need for caution in experiments using high concentrations of conjugates. They suggest that PLAP may be a suitable target for immunotoxin therapy of human cancer. PMID- 2579738 TI - Distribution of galanin-like immunoreactivity in the gastro-intestinal tract of several mammalian species. AB - The distribution of galanin-immunoreactive (GAL-IR) neurons was mapped in detail in the gastro-intestinal tract of the rat, mouse, guinea-pig and pig by use of the indirect immunofluorescence technique. GAL-IR cell bodies were found in both the submucous and the myenteric plexus, with considerably higher numbers in the former ganglia. The largest number of GAL-IR perikarya was seen in the duodenal submucous plexus of the pig. With some (single) exceptions, GAL-IR cell somata were not observed in the myenteric plexus of the pig and guinea-pig, and in the submucous plexus of the esophagus and the stomach of the guinea-pig. GAL-IR fibers occurred in most parts of the gastro-intestinal tract. In the lamina propria a few non-varicose, weakly fluorescent fibers were noted in the mouse and rat, whereas in the pig and guinea-pig were large numbers of GAL-IR fibers with a varicose appearance was observed. These fibers were in all species most numerous in the distal portion of the intestinal tract. In the submucosa GAL-IR fibers were detected in all four species, and in the pig and guinea-pig some fibers surrounded blood vessels. A large number of GAL-IR fibers was generally seen in the circular smooth muscle layer, except in the guinea-pig, which only seemed to contain a few fibers. In the longitudinal muscle layer only single fibers could be detected. However, the gastric fundus region of the pig contained a moderate number of fibers in the longitudinally and obliquely oriented layers. In general, in the rat, mouse and pig, the submucous and myenteric plexus contained moderate or large numbers of GAL-IR fibers. In the guinea-pig, no or only single fibers were observed in the plexus of the upper gastro-intestinal tract and the rectum, while moderate numbers were seen in the ileum and colon. Thin adjacent sections stained for vasoactive intestinal polypeptide (VIP) and GAL revealed the coexistence of these two peptides in cell bodies of the myenteric plexus in the pig duodenum and guinea-pig colon. In these two species the GAL- and VIP-nerve fiber networks also exhibited marked similarities. However, in the rat and mouse VIP- and GAL-distribution patterns were in general different. The present findings indicate the presence of yet another neuropeptide or peptide family in the gastro-intestinal tract of several rodents and the pig. PMID- 2579740 TI - The thermodilution technique in on-line computation of the left ventricular volumes on anaesthetized dogs. AB - The thermal dilution technique and its suitability for automatic computation of left ventricular volumes were evaluated on 28 anaesthetized dogs. The end diastolic volume (EDV) was computed from ventricular washout curves in two ways, first utilizing the ratio between the indicator amount and its peak concentration (first ejection method); and secondly the ratio between stroke volume and ejection fraction with the latter obtained by subtracting the residual fraction from 1.0. The residual fraction was determined as the mean of ratios between successive steps of four ventricular ejections on the downslope of the curve (downslope method). The linear correlation coefficient between the EDV determinations (n = 366) was 0.926, and slope y = 1.14 X + 0.5 ml with 4.6 ml as standard error of estimate. The first ejection method gave on average 15% higher EDV values than the downslope method. When heart rate was increased by pacing from 88 to 240/min, both methods showed a reduction of the EDV, but the downslope method to a greater degree. When afterload was increased but heart rate decreased by phenylephrine, the first ejection method but not the downslope method indicated an increase in EDV. Otherwise, when pronounced tachy- or bradycardia were avoided, ventricular volumes yielded by the two methods were comparable. Indicator injection did not substantially affect ventricular pressure dynamics. The first ejection method seems to be a simple means for repeated measurements of EDV even in the case of diseased hearts. PMID- 2579739 TI - Studies of the guinea-pig epididymis. III. Innervation of epididymal segments. AB - The innervation of the ductuli efferentes and seven zones of the guinea-pig epididymis was investigated using immunohistochemical, histochemical and electron microscopical techniques. Nerve fibers were localized by use of antibodies against substance P (SP-IR), vasoactive intestinal polypeptide (VIP-IR) and dopamine-beta-hydroxylase (DBH-IR). In the ductuli efferentes and all zones of the epididymal duct, SP-IR is consistently observed in the interstitial tissue and perivascular areas. Histochemistry reveals a significant amount of acetylcholinesterase-containing fibers in the interstitial, perivascular and periductal smooth muscles of the ductuli efferentes and zones V, VI and VII. In contrast to the homogeneous distribution of SP-IR within all zones of the epididymis, VIP-IR is seen only in zones VI and VII. Within these zones, VIP-IR is detected in large amounts in the subepithelial and muscular layers as is a sparse number of SP-IR varicosities. DBH-IR is also seen throughout all zones in the interstitial and perivascular regions with a tendency to increase in zones VI and VII. Transmission electron microscopy (TEM) reveals evidence of a cholinergic (agranular vesicles, AGV), adrenergic (small granular vesicles, SGV) and peptidergic (large granular vesicles, LGV) innervation throughout the interstitial connective tissue of the ductuli efferentes and all epididymal zones. Furthermore AGV are localized in the subepithelial layer, and also co stored with LGV in the muscular layer of zones VI and VII. No nerve profiles were encountered within the epithelium. A correlation of immunohistochemical findings to TEM counterparts as well as their possible functional role are discussed. PMID- 2579741 TI - All hepatocytes are involved in the expression of the albumin gene in the normal adult rat: a demonstration by in situ hybridization and immunoperoxidase techniques. AB - Immunoperoxidase techniques have yielded conflicting results concerning the percentage of hepatocytes engaged in albumin production in normal adult rats. In addition, the question of whether functional differences in the synthesis of plasma proteins exist within the hepatic lobule remains to be determined. To clarify these questions, we have searched for gene albumin transcripts by in situ hybridization, and for the corresponding protein by immunoperoxidase, on adjacent liver sections. We observed that all hepatocytes contain albumin transcripts as well as the albumin protein, without any detectable zonal variation within the liver lobule. Taken altogether, these results demonstrate that every hepatocyte, whatever its location in the hepatic lobule, is actively engaged in albumin gene expression. PMID- 2579742 TI - Proliferation of multinucleate cells with unbalanced nuclei. AB - When onion root meristems are treated with gamma-hexachlorocyclohexane the anaphase chromatids are distributed in discrete unbalanced groups and subsequent inhibition of cytokinesis in these cells produced a synchronous population of viable multinucleate cells with two, three of four aneuploid nuclei. When we compare the duration of G1, S and G2 periods in diploid cells with that obtained for multinucleate cells in the present study it seems clear that the differences, if they occur, are negligible. These results are consistent with the hypothesis that the cell mass/genome ratio can play an essential role in controlling cycle rate and that most of the genic requirements for interphase development must complement between the nuclei sharing a common cytoplasm, even though some factor inside every nucleus appears to be required for replicative capacity to be effective. PMID- 2579743 TI - [The importance of studying pancreatic amylase induction in children of diabetic mothers]. PMID- 2579744 TI - [Analysis of 38 cases of prostatic hypertrophy treated with bilateral orchiectomy and traditional Chinese medicine promoting yang for diuresis]. PMID- 2579745 TI - Immunohistochemical study of keratin in proliferative bladder epithelium induced by freezing, cyclophosphamide or N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide in the rat. AB - The distribution of intracellular keratin proteins was examined in a variety of urinary bladder lesions of the rat using the immunoperoxidase staining technique. In ethanol-fixed sections, the normal epithelium was strongly positive for keratin staining. Focal regenerative hyperplasia of the bladder epithelium induced by freezing exhibited relatively weak staining. However, diffuse regenerative hyperplasia induced by a single intraperitoneal injection of cyclophosphamide (CP) showed an intensely positive reaction throughout the epithelium. Of the sections fixed with Bouin's solution, the staining reaction was drastically reduced in the normal bladder and the staining was totally negative in the regenerative hyperplasia caused by freezing. Simple hyperplasia induced by a 4-week feeding of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) as 0.2% of the diet exhibited strong reactivity, and nodular and papillarly hyperplasia induced by a 10-week feeding of FANFT was also positive for keratin throughout the lesions. In contrast to the preneoplastic lesions, FANFT-induced transitional cell carcinoma showed differential staining within the tumors. These results suggest that different keratin expression is involved in the proliferative bladder lesions induced mechanically by freezing and chemically by CP or by the carcinogen FANFT. PMID- 2579746 TI - New studies of the excitatory sodium currents in heart muscle. AB - After decades of frustration with inadequate methods, cardiac electrophysiologists have developed new techniques for superior control of membrane potential by use of single cells, and they have begun careful study of cardiac Na+ currents. Direct recordings of the behavior of single Na+ channels have been made by the newly developed patch clamp technique. Biochemists have made excellent progress purifying and characterizing the Na+ channel proteins, and there has been some initial success in reconstituting these partially purified channels into lipid bilayers, where their function can be studied. Even at this early stage of development of these new techniques, several conclusions are warranted: The cardiac Na+ currents are not accurately described by the original Hodgkin-Huxley mathematical formulation, making undesirable the further use of this model for study of cardiac excitation and conduction. We need to keep an open mind as to the kinetic behavior of Na+ channels, until the newer experimental techniques provide a more complete picture. Although the cardiac Na+ channel strongly resembles Na+ channels in other excitable tissues, important differences remain, reinforcing the idea that the detailed molecular structure of the cardiac Na+ channel will be different from its close relatives in other excitable cells. The density of Na+ channels in heart cell membranes is much less than in nerve and fast twitch skeletal muscle. The Na+ channels are the focus of action of many drugs and pathological processes. The tools are at hand for a complete description of the Na+ channel, including its gating and its molecular structure. We can expect considerable progress in this decade. PMID- 2579747 TI - Evidence for a specific receptor site for lidocaine, quinidine, and bupivacaine associated with cardiac sodium channels in guinea pig ventricular myocardium. AB - According to the modulated receptor hypothesis, sodium channels have a specific receptor site for local anesthetic and antiarrhythmic drugs. Thus, in the presence of a high concentration of two drugs, competitive displacement of one drug by another may occur. Furthermore, if a drug that has relatively rapid post stimulation recovery kinetics (e.g., lidocaine) displaces another drug with relatively slow recovery kinetics (i.e., quinidine or bupivacaine), then a net reduction in sodium channel blockade is expected at certain stimulation rates. We tested this prediction, using the maximum upstroke velocity of the ventricular action potential as an indicator of drug-free sodium channels. A single sucrose gap technique was used to stimulate guinea pig papillary muscles, and to control membrane voltage at all times except during the action potential upstroke. Drug induced inhibition of maximum upstroke velocity increased as the stimulation rate was increased, and was significant (P less than 0.05) at stimulation rates between 2.5 and 4 Hz in the presence of 43 microM lidocaine (n = 5), and between 0.15 and 4 Hz in the presence of 3.5 microM bupivacaine (n = 4). The addition of 43 microM lidocaine to a perfusate containing 3.5 microM bupivacaine resulted in a net increase in maximum upstroke velocity that was significant at rates between 1 and 3.3 Hz, with a maximum increase of 25 +/- 6% at 1.6 Hz. In contrast, addition of 43 microM lidocaine to a perfusate containing 15 microM quinidine did not result in a significant change in maximum upstroke velocity at driving rates between 0.05 and 3.3 Hz (P greater than 0.2; n = 4). However, evidence for displacement of quinidine by lidocaine could be demonstrated by measuring post stimulation recovery after a conditioning train of 19 10-msec pulses applied at 28 Hz. With this stimulation protocol, 41 +/- 4% of maximum upstroke velocity recovered slowly from block with a time constant of 3.7 +/- 1.2 seconds at - 100 mV in the presence of 15 microM quinidine (n = 5). In the presence of a mixture of 43 microM lidocaine and 15 microM quinidine, this slow component was significantly reduced to 16 +/- 7% (n = 5; P less than 0.01), while 71 +/- 13% of maximum upstroke velocity recovered with a time constant of 115 +/- 21 msec, typical of lidocaine-blocked channels. A two-drug version of the modulated receptor theory was formulated. The effects of drug mixtures could be accounted for by this model.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2579748 TI - Calcium-dependent fluxes of potassium-42 and chloride-36 during norepinephrine activation of rat aorta. AB - This study was designed to determine whether alpha-receptor-stimulated monovalent ionic fluxes in rat aorta required calcium, and, if so, whether both extracellular calcium and cellularly stored calcium are active. Calcium removal in the presence of 10 mM magnesium (to maintain membrane stability) inhibited the norepinephrine-stimulated increase in potassium-42 and chloride-36 efflux. However, the norepinephrine-stimulated increase in sodium-24 influx was relatively resistant to calcium depletion. Protocols were designed to measure the time course for the changes in potassium-42 efflux and contraction when calcium was removed or replaced in the presence of norepinephrine. The dose-dependent effect of a calcium antagonist (diltiazem) was also measured. A close correlation (r = 0.94) was found between inhibition of contraction and potassium-42 effluxes which followed the regression: % potassium-42 response = 1.0 X (% contraction) + 1.8%). The slope of 1.0 and intercept near zero suggests the hypothesis that norepinephrine-stimulated potassium-42 efflux and contraction are codependent on cellular calcium concentration. This co-dependence held for short phasic responses (approximately 1 minute), as well as longer tonic responses (greater than or equal to 5 minutes). It appears that calcium-dependent potassium-42 effluxes can be supported by both the influx of extracellular calcium and release of cellular stores. It is concluded that calcium-dependent potassium channels (and possibly chloride channels) are operative in rat aorta and are an important component of the graded membrane response to norepinephrine. The sodium channels, however, do not appear to share this same calcium dependency. PMID- 2579749 TI - Differential effects of central angiotensin II and substance P on sympathetic nerve activity in conscious rats. Implications for cardiovascular adaptation to behavioral responses. AB - The centrally induced effects of angiotensin II and substance P on the cardiovascular system and on neuronal efferent activity of the splanchnic, renal, and adrenal nerves were investigated in chronically instrumented conscious rats. The pressor responses to substance P injected into the lateral brain ventricle were accompanied by marked and short latency increases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a rise in plasma noradrenaline and adrenaline. Behaviorally, an arousal-type reaction was observed. In contrast, the pressor responses to intracerebroventricular angiotensin II were associated with initial decreases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a fall in plasma noradrenaline at the time of the maximal blood pressure increase. In some but not all animals, a second blood pressure peak associated with increases in heart rate and splanchnic nerve activity was observed after several minutes. Incomplete chronic sinoaortic baroreceptor deafferentiation prevented the angiotensin II induced fall in heart rate but not the initial fall in splanchnic nerve activity. The decreases in splanchnic nerve activity also occurred in diabetes insipidus rats and persisted in Long Evans rats after vascular vasopressin receptor blockade with d(CH2)5AVP, despite marked reductions of the pressor responses in both groups. Peripheral alpha-adrenoceptor blockade with prazosin or ganglion blockade with hexamethonium inhibited the central angiotensin II pressor responses only in combination with vasopressin receptor blockade. On the other hand, either sympatholytic drug, alone, abolished the pressor responses in the diabetes insipidus rats. This indicates that in intact conscious rats the central pressor effects of angiotensin II are initiated by vasopressin release but become dependent on the sympathetic nervous system when vasopressin is absent or not effective. When rats were allowed to drink in response to angiotensin II, a further sharp rise in blood pressure occurred, together with increases in heart rate and splanchnic nerve activity. The results demonstrate fundamental differences in the mechanisms by which central pressor peptides can influence cardiovascular and autonomic function. It is conceivable that the distinct sympathetic response patterns to central angiotensin II and substance P receptor stimulation form part of a specific cardiovascular adjustment to the individual behavioral reactions, such as drinking, as in the case of angiotensin II, or arousal within the central processing of pain, as in the case of substance P. PMID- 2579750 TI - Amniotic fluid acetylcholinesterase activity and alpha-fetoprotein in chromosomal anomalies and neural tube defects. AB - Measurement of alpha-fetoprotein concentration and acetylcholinesterase activity in amniotic fluid can be used to identify chromosomal defects as well as neural tube defects. In seven cases of trisomy 21 and one case of partial trisomy 3, alpha-fetoprotein concentrations were below the reference range but values for acetylcholinesterase activity were normal for the appropriate gestational age. One case of trisomy 13 had an increase in acetylcholinesterase activity and normal alpha-fetoprotein concentration. PMID- 2579751 TI - 5-Azacytidine treatments in the characterization of a t(1;21)(q12;q22) carrier karyotype. AB - A 46,XX,t(1;21)(q12;q22) carrier was ascertained because of two abortions. The non-reciprocal nature of the rearrangement was demonstrated in 5-azacytidine treated preparations with highly decondensed and somatically paired heterochromatic regions. PMID- 2579752 TI - Detection of the common acute lymphoblastic leukaemia antigen (CALLA) on B cells from human fetal tissues. A multiple phenotypic characterization. AB - Fetal bone marrow liver and spleen of gestational age 15-20 weeks contain CALLA+, HLA-DR+ lymphoid cells. We show that a proportion of them expresses surface membrane immunoglobulins (SIg) as well as B cell differentiation antigens. A multiple phenotypic analysis reveals that CALLA+ fetal B cells are: HLA-DR+, SIg+, FMC8+, BA1+, Y29.55+ or Y29.55-, B2+, TdT-. Tissue specific phenotypic differences concern the expression of B7 and HLA-DC on spleen but not on bone marrow B cells. This study indicates that the distribution of the CALL antigen across the B cell committed lineage is much wider in fetal than neonatal life since CALLA+B cells have not yet been detected in bone marrow and peripheral blood of normal infants and adults. In addition, the interpretation of our phenotypic data suggest that fetal bone marrow B cells are more immature than those present in the spleen, thus, further supporting the evidence that the bone marrow is the organ of B cell lymphopoiesis. PMID- 2579753 TI - Specificity and duration of post-inflammatory suppression in rabbit lungs challenged with aerosolized antigen. AB - Rabbits immunized and aerosolized with soluble protein antigens develop a short lived pulmonary inflammation. This is followed by a period of non-specific unresponsiveness which lasts approximately 30 weeks after the first exposure to aerosol treatment. This period is characterized by the inability of the rabbit to exhibit another inflammatory reaction either to the same antigen used to induce the first inflammation, or to a new antigenically unrelated antigen. After 30 weeks however, the animals become responsive (develop another pulmonary inflammation) to a second unrelated antigen, but remain unresponsive to the antigen used to elicit the initial inflammatory response. These studies indicate that following challenge with inhaled antigen, rabbits develop a non-specific suppression of pulmonary inflammation which lasts a finite period of time. When this disappears, the animal is left with an antigen specific suppression of pulmonary inflammation. These studies suggest a model for normal individuals who may respond similarly to potentially harmful inhaled allergens. Individuals with hypersensitivity pneumonitis, however, may not develop antigen specific unresponsiveness. The nature of this unresponsiveness is unknown at present, nor is it known when it begins to develop. PMID- 2579754 TI - Serum antibodies against central nervous system proteins in human demyelinating disease. AB - An immunoblotting technique has been used to screen serum samples from patients with demyelinating disease for antibody directed against central nervous system proteins. Antibodies of the IgM, IgG and IgA class directed against one or more of the particulate fraction proteins tubulin, myelin basic protein, 69 K neurofilament protein, glial fibrillary acidic protein, myelin associated glycoprotein or Wolfgram protein were present in 94, 54 and 47%, respectively, of multiple sclerosis sera examined. IgM antibodies against tubulin and myelin basic protein predominated. A similar antibody spectrum was seen in a significant proportion of sera from patients with optic neuritis, subacute sclerosing panencephalitis and motor neurone disease, in which primary or secondary demyelination occurs. Antibodies of all three classes directed against the 169 K and 220 K neurofilament proteins and against some unidentified proteins of human peripheral nerve, kidney, liver, spleen and skeletal muscle were detected in sera from healthy subjects and patients with neurological disease. PMID- 2579755 TI - Deficient immune interferon production in tuberculosis. AB - Production of interferon (IFN)-alpha and -gamma by peripheral blood mononuclear cells (PBMC) were studied in 28 patients with active tuberculosis and 28 healthy control subjects matched for age, sex, ethnic origin and diet. No significant differences were found between patients and matched controls in mean titres of IFN-alpha induced by Newcastle disease virus, IFN-gamma induced by staphylococcal enterotoxin A with tetrahydrophorbyl acetate, and IFN-gamma induced by purified protein derivative (PPD). However, a subset of nine out of 25 tuberculosis patients tested produced low titres (less than 100 u/ml) of IFN-gamma in response to PBMC stimulation with PPD. In comparison to other patients, this group was characterized by lower IFN-alpha and IFN-gamma responses to virus and mitogens respectively, relative anergy to tuberculin skin testing, depressed in vitro PBMC proliferative responses to PPD, and neutrophil leucocytosis. In all nine patients effective chemotherapy restored cutaneous reactivity, PBMC proliferative responses, neutrophil counts and IFN-alpha responses to virus by 6 months, and also IFN-gamma responses to PPD in one patient re-tested. PMID- 2579757 TI - Treatment of acute gouty arthritis with piroxicam. AB - Piroxicam is a nonsteroidal anti-inflammatory drug currently available for the treatment of various rheumatic diseases. Twenty-eight patients with acute gouty arthritis were treated with a single daily dose of 40 mg piroxicam for a period of 5 days. The majority of patients showed rapid improvement with analgesic effectiveness demonstrated 3 hours after first dose administration. No significant side affects were observed. On the basis of this study, piroxicam was found to be an effective medication for the treatment of acute gouty arthritis. PMID- 2579756 TI - Anti-phospholipid antibodies in syphilis and a thrombotic subset of SLE: distinct profiles of epitope specificity. AB - In a study of connective tissue and infectious disease sera, we have demonstrated IgM and IgG anti-cardiolipin activity, in a solid phase radioimmunoassay, in systemic lupus erythematosus (SLE), rheumatoid arthritis, syphilis and in acute malaria caused by four different species of Plasmodium. The highest values were noted in SLE (IgM anti-cardiolipin P less than 0.005, IgG anti-cardiolipin P less than 0.01), but there was no correlation with anti-dsDNA, rheumatoid factor or VDRL titres in any disease group. Anti-cardiolipin binding was significantly associated with the lupus anticoagulant, thrombocytopenia, spontaneous abortions and thromboses in the SLE patients. Ten SLE sera from this thrombotic subset and 10 syphilitic sera with similar anti-cardiolipin activity, were tested against four phospholipid antigens and showed significantly different anti-phosphatidyl ethanolamine/anti-phosphatidyl serine binding ratios (P less than 0.001). These differences in phospholipid epitope specificity could explain the specificity of the VDRL antigen in syphilis serology, and we discuss a putative role for anti phosphatidyl serine in the thrombotic diathesis of SLE. PMID- 2579759 TI - Adrenaline and ion flux in isolated human leucocytes. AB - Hypokalaemia may be produced in man by intravenous adrenaline infusion, or as a result of pathological disturbances which have led to a high plasma adrenaline concentration. With isolated human leucocytes used as a cellular model, adrenaline at concentrations at and above 9 nmol/l increases the influx of rubidium (a model for potassium flux) into cells, with a simultaneous efflux of sodium. There is no effect on Na+,K+-ATPase activity in lysed leucocytes. Use of the adrenoceptor blockers timolol and atenolol shows that the demonstrated effect of adrenaline on coupled active transport of ions is mediated by beta 2 adrenoceptors. PMID- 2579758 TI - Interferon treatment of chronic rubella associated arthritis. PMID- 2579760 TI - Holter monitoring in the management of cardiac arrhythmias in children. PMID- 2579761 TI - Cardiovascular and autonomic effects of muscle relaxants. PMID- 2579762 TI - Production and characterization of monoclonal antibodies to bovine skin proteodermatan sulfate. AB - To study the molecular structure and function of bovine skin proteodermatan sulfate, on a determinant by determinant basis, several monoclonal antibodies to this molecule have been produced and characterized. Based on the results of a preliminary immunogenetic analysis of 4 inbred mouse strains, SJL/J (H-2s) mice were immunized for the fusions. Ten hybridomas were produced and the monoclonal antibodies from four of these were selected for further investigation. Employing an ELISA inhibition assay, none showed any detectable affinity for bovine collagen types I, II, III, or IV, bovine fibronectin or chondroitin or dermatan sulfate glycosaminoglycans. Each monoclonal antibody bound the chondroitinase ABC derived protein core and none was significantly inhibited by proteinase digests of the intact molecule suggesting that the epitope of each contains a protein component. The results of competitive binding ELISA assays and immunoblots of the cyanogen bromide cleavage products of proteodermatan sulfate indicate that the 4 antibodies recognize at least 3 distinct antigenic determinants on this molecule. Immunohistochemical methods located the antigen in the dermis of bovine skin and revealed that a change in proteodermatan sulfate distribution occurs during skin development. PMID- 2579763 TI - Seasonal fluctuations in plasma protein fraction levels of chinchillas (Chinchilla laniger, M.). AB - Seasonal changes in blood plasma protein fractions in chinchilla females and males were found. Plasma albumin levels in both sexes vary according to season, generally low in winter and spring and high in summer and autumn. The levels of alpha 1-globulin and gamma-globulin increase markedly in spring (1.5 times higher than in winter and autumn). In chinchilla females, the levels of alpha 2-globulin and beta 2-globulin varied biphasically, being higher in winter and summer. In males, clear seasonal trends in the levels of both fractions were not observed. The beta 1-globulin fraction levels vary throughout the year. In females as well as males, globulin decreases during winter to minimal values in late spring, and then increases again during the summer to remain at the same level till autumn. PMID- 2579764 TI - Light-evoked depolarizations in the retina of Strombus: role of sodium and potassium ions. AB - Light-evoked depolarizations (LED's) in retinal cells of Strombus luhuanus can exhibit an early phase of depolarization (DE), a brief repolarizing phase (RE), and a later depolarizing phase (DL). Lowering external Na+ by substitution with choline, tetramethylammonium or sucrose, reduced the amplitude of the entire LED, but DL was reduced more than DE. Replacement of Na+ with Li+ reduced DE more than DL. Lowering pH reduced DL more than DE, while raising it increased DL but not DE. K+ channel blocking agents, tetraethylammonium and 4-aminopyridine, increased RE. During the LED, cell membrane conductance increased in two phases, corresponding to DE and DL. The results suggest LED generation by two separable conductance increases to Na+, corresponding to DE and DL, and another to K+ during RE. PMID- 2579765 TI - Disappearance of dextran 70,000 from plasma of hamadryas baboons. AB - Evans Blue (EB), [131I]human albumin and [14C]dextran 70,000 were injected into three water repleted and water depleted hamadryas baboons, in order to evaluate the permeability of their capillary bed under these conditions. The rate of disappearance of dextran from the plasma is significantly higher than that of the other markers, despite its relatively high molecular weight. Half-life values of EB and albumin in water depleted baboons were significantly higher than values in water repleted animals. Inulin and dextran showed no significant difference before or after dehydration. Chromatography of urine and plasma samples on columns of Sephadex G-75 showed that dextran passed the glomerular capillaries and is excreted into the urine with its same original molecular size. The permeability of capillary beds to dextran 70,000 is negligible. The fact that the kidneys excrete dextran means that dextran 70,000 is not a useful marker for calculating the capillary permeability in hamadryas baboons. PMID- 2579767 TI - The role of proctolin and glutamate in the excitation-contraction coupling of insect visceral muscle. AB - Proctolin (1 X 10(-10) to 1 X 10(-9) M) had a minimal effect on the spontaneous and evoked electrical events of the hindgut of the cockroach Leucophea maderae. Spontaneous action potentials and contractile activity stopped when the hindgut was exposed to 2 mM Mn2+. Eighty per cent of the response of the hindgut to glutamate was blocked by manganese, but only 35% of the response to proctolin. Hindguts were responsive to proctolin in a calcium-free medium, but not to glutamate. Moreover, proctolin appeared to facilitate the reentry of calcium after depleted preparations were returned to normal levels of external calcium. The results offer evidence for two calcium transmembrane channels in insect visceral muscle. PMID- 2579766 TI - Acetylcholine responses of identified neurons in Helix pomatia--III. Ionic composition of the depolarizing currents induced by acetylcholine. AB - The ionic composition of the currents underlying the acetylcholine (ACh) depolarizations in the identified neurons B1 and B3 of the buccal ganglia of Helix pomatia was analysed. The equilibrium potential of the ACh responses was 2.8 +/- 0.6 mV (N = 49) and -4.0 +/- 0.7 mV (N = 79; mean +/- SEM) in the neurons B1 and B3, respectively. Replacement of NaCl in the bath solution by sucrose shifted the ACh equilibrium potential into the negative direction. A similar but less pronounced shift occurred when Ca2+ was substituted for Na+. Substitution of Cl- in the bath solution by propionate or an increase of the intracellular Cl- concentration did not affect the ACh equilibrium potential. Changes of K+ concentration in the bath between 1 and 50 mmol/l left the ACh equilibrium potential nearly unaffected when the Na+ concentration was at the control level. With a simultaneous reduction of extracellular Na+ an increase of K+ concentration shifted the ACh equilibrium potential towards more positive potentials. The findings are compatible with calculated K+ permeabilities if a K+ redistribution across the cell membrane is considered. In the neurons B1 and B3, channels operated by ACh are permeable for K+, Na+ and Ca2+, with the relative permeabilities 1.6:1.0:0.1. PMID- 2579768 TI - T-cell factors that promote B-cell proliferation and differentiation. PMID- 2579770 TI - Platelet cryopreservation with glycerol, dextran, and mannitol: recovery of 5 hydroxytryptamine uptake and hypotonic stress response. AB - Human platelets were frozen in 0.5 M glycerol, 0.5 M glycerol + 3% Dextran T40, or 0.5 M glycerol + 5% mannitol. The recovery of active transport of 5 hydroxytryptamine (5-HT) and the hypotonic stress response after freezing were dependent on the rate of cooling: the optimum range of rates was between 12 and 23 degrees C/min. The numerical recovery of cells was independent of cooling rate, but freezing altered the cell-size distribution. The combination of dextran and glycerol was no better than glycerol alone at protecting platelets against freezing damage. Mannitol, however, adversely affected platelet 5-HT uptake, and this was reflected in a low recovery of that activity after freezing platelets in glycerol supplemented with mannitol. PMID- 2579769 TI - Signal mechanisms of phototransduction in retinal rod. AB - The levels of intracellular molecules are modulated by illumination of rod photoreceptor cells in the vertebrate retina. Among these are Ca ions, cyclic nucleotides (cGMP in particular), and phosphate nucleotides (ATP and GTP). It is presumed now that at least two of these molecules, Ca and cGMP, may function as chemical linkers between the absorption of light by rhodopsin and the ionic channels of the plasma membrane of the rod outer segment that close when the rod is illuminated. The manuscript will review the physiology of the rod cell, the evidence in support of light-dependent changes in the intracellular levels of various small molecules, and the role of these changes in coupling rhodopsin excitation to the control of the light-sensitive membrane channels in the rod. PMID- 2579771 TI - Monoclonal antibodies to proteokeratan sulfate of rabbit corneal stroma. AB - Hybridomas were developed that secreted monoclonal antibodies against two proteokeratan sulfates (PKS) from rabbit corneal stroma. A total of 28 antibodies were isolated, all of the IgG type with kappa light chains. All were found to react with both PKSs. As judged by immunohistochemical staining, none of them reacted with scleral or conjunctival components, nor with sections of skin, but all reacted with nasal cartilage. When tested by enzyme-linked immunosorbent assays, against components of the proteoglycans, all of the antibodies reacted with keratan sulfate-peptide (isolated from papain digests of PKS or of cartilage proteoglycan), and all but two reacted with oligosaccharide-containing protein cores (prepared by keratanase treatment of PKS). Reactivity with cores was probably due to residual portions of the keratan sulfate chains since the endogenous oligosaccharide-peptides (non-sulfated, non-keratan sulfate oligosaccharides isolated after papain digestion of PKS) were not active. None of the antibodies reacted with protein cores made by removal of carbohydrate by hydrolysis with trifluoromethanesulfonic acid. All except one reacted with fragments of keratan sulfate (made by keratanase digestion). These observations are evidence for structural requirements at three different levels of completeness of the antigen for recognition among the various antibodies. In addition, none of the antibodies reacted immunohistochemically with macular dystrophic corneas, confirming the finding of others that the defect lies in the keratan sulfate portion of the proteoglycans. PMID- 2579772 TI - Molecular biology of human T-cell leukemia virus associated with adult T-cell leukemia. PMID- 2579773 TI - Structure and function of the genome of HTLV. PMID- 2579774 TI - Human T-cell leukemia/lymphoma virus: studies of host-virus interaction. PMID- 2579775 TI - YAG laser therapy. New techniques and conventional wisdom. PMID- 2579776 TI - Neodymium-YAG laser treatment of intrabronchial lesions. A new mapping technique via the flexible fiberoptic bronchoscope. AB - We report the results of the treatment of 45 patients (38 with malignant and seven with benign disease) with intrabronchial lesions using the neodymium-YAG laser via the flexible fiberoptic bronchoscope. Multiple treatment sessions were used with treatment intervals varying from four days to four weeks. Additional debridement procedures were also necessary in select cases. (There was total of 109 treatments in 45 patients). Over 70 percent (81 of 109) of all treatments were done without intubation and with sedation techniques, and topical lidocaine application similar to that used in standard fiberoptic bronchoscopy. Laser treatment of the less extensive segmental lesion resulted in very meaningful palliation and laser therapy need not be reserved for extensive central disease only. In our judgment, this can most safely be done with a "real time, intrabronchial mapping technique." The Mill Rose (W-22-13) transbronchial needle was used intraoperatively to perforate blind intrabronchial obstructions. Renografin (Ren-M-60 M) was then hand injected to locate and fluoroscopically visualize the postobstructive bronchial remnant. Precise laser penetration into the postobstructive remnant was then possible by following the same pathway. This technique greatly extended our ability to safely perforate segmental and even blind central obstructing lesions. In our judgment, without a "real time intrabronchial mapping technique," vascular and bronchial perforations would be more likely when treating the more distal lobar and segmental obstructions. PMID- 2579777 TI - Differential gene activity visualized on sister chromatids after replication in the presence of 5-azacytidine. AB - Mitotic chromosomes with sister chromatids bearing differentially active ribosomal gene clusters were recovered from human lymphocytes exposed to 5 azacytidine. The hypothesis was that the differential activity was determined by the hypomethylation of one of the two sister chromatids. The verification was carried out by "labeling" the 5-azacytidine-substituted chromatid with BUdR, and then checking the location of active clusters by specific staining techniques. Data obtained confirmed that the chromatid bearing the active cluster was indeed the 5-azacytidine-substituted one. PMID- 2579779 TI - [Problems concerning the mouse micronucleus test]. PMID- 2579778 TI - Identification of a family of human centromere proteins using autoimmune sera from patients with scleroderma. AB - We have examined "preimmune" serum samples from a patient who progressively developed the symptoms of scleroderma CREST over a period of several years. During this period, anti-centromere antibodies (recognized by indirect immunofluorescence) appeared in the serum. Concomitant with the appearance of the anti-centromere antibodies, antibody species recognizing three chromosomal antigens in immunoblots of SDS polyacrylamide gels appeared in the patient's serum. These antigens migrate with electrophoretic mobilities corresponding to Mr = 17, 80, and 140 kilodaltons (kd). Affinity-eluted antibody fractions recognizing the antigens have been prepared from sera of three other patients. Indirect immunofluorescence labeling of mitotic cells using these antibody fractions demonstrates that the antigens are centromere components. We designate them CENP (CENtromere Protein) - A (17kd), CENP-B (80kd), and CENP-C (140kd). The three CENP antigens share antigenic determinants. Immunoblotting experiments show that these patients make antibody species recognizing at least three distinct epitopes on CENP-B and two on CENP-C. Sera from different patients contain different mixtures of the antibody species. PMID- 2579780 TI - Flow cytometric analysis and sorting of human endometrial cells after immunocytochemical labeling for cytokeratin using a monoclonal antibody. AB - Endometrial cells in suspension were stained with propidium iodide and a monoclonal antibody against a cytokeratin intermediate filament protein specific for glandular and columnar cells (RGE 53). In this way columnar epithelial cells of the normal endometrium and of adenocarcinomas can be distinguished and separated by flow cytometry from non-epithelial cells (fibroblasts and inflammatory cells) and squamous epithelial cells, all of which are negative for RGE 53. This makes it possible to analyse and also sort pure fractions of this particular tissue type for further studies. The use of propidium iodide allows simultaneous DNA flow cytometry of these columnar epithelial cells. Therefore, the use of antibodies to cytokeratin in combination with propidium iodide can be of help in analyzing and sorting pure fractions of both normal and malignant cells. This allows a more refined examination of complex cell mixtures using flow cytometry. PMID- 2579782 TI - [Follow-up analysis of persistent low positive serum alpha-fetoprotein (AFP)- report on 420 cases]. PMID- 2579781 TI - Preparation and bivariate analysis of suspensions of human chromosomes. AB - Chromosomes were isolated from a variety of human cell types using a HEPES buffered hypotonic solution (pH 8.0) containing KCl, MgSO4, dithioerythritol, and RNase. The chromosomes isolated by this procedure could be stained with a variety of fluorescent stains including propidium iodide, chromomycin A3, and Hoechst 33258. Addition of sodium citrate to the stained chromosomes was found to improve the total fluorescence resolution. High-quality bivariate Hoechst vs. chromomycin fluorescence distributions were obtained for chromosomes isolated from a human fibroblast cell strain, a human colon carcinoma cell line, and human peripheral blood lymphocyte cultures. Good flow karyotypes were also obtained from primary amniotic cell cultures. The Hoechst vs. chromomycin flow karyotypes of a given cell line, made at different times and at dye concentrations varying over fourfold ranges, show little variation in the relative peak positions of the chromosomes. The size of the DNA in chromosomes isolated using this procedure ranges from 20 to over 50 kilobases. The described isolation procedure is simple, it yields high-quality flow karyotypes, and it can be used to prepare chromosomes from clinical samples. PMID- 2579783 TI - [tRNA as an activator of protein kinase induced by interferon]. PMID- 2579784 TI - [Long-term therapy of cancer pain. A controlled study on buprenorphine]. AB - Sublingual tablets of buprenorphine (Temgesic sublingual) were given in a controlled trial of 41 patients for 2804 patient-days. With a mean starting dose of 1.09 mg and a final dose of 1.53 mg buprenorphine daily there was a good pain relieving effect. The interval between doses was six to eight hours. The trial did not reveal any direct pointers as to tolerance or addictiveness after long term intake of the drug. Because of its effectiveness and good duration of action, as well as the absence of negative long-term effects, the drug can be recommended in the long-term management of cancer pain. PMID- 2579785 TI - [Ascites. Current aspects of diagnosis and therapy]. PMID- 2579787 TI - [Use of the Steinbuch learn matrix for the formation of a regression model with binary variables]. PMID- 2579786 TI - [Oncogenes and cancer chemotherapy with interferons]. PMID- 2579788 TI - [Fetal and placental proteins]. PMID- 2579789 TI - [Interferon research at home and elsewhere]. PMID- 2579790 TI - [Ion channels and neurotransmission]. PMID- 2579791 TI - [Regulation of angiogenesis and tumor growth]. AB - The data on tumour vascularization regulating substances, their structure and mechanism of action are reviewed. The systems for testing angiogenic reactions are analyzed. The role of mast cells, lymphocytes, macrophages and leucocytes in formation of new microvessels is under discussion. The results of the search for antitumor drugs inhibiting angiogenesis are promising. The data are analyzed on the role of prostaglandins, Cu2+ and urokinase in the processes of tumour vascularization. The possibility of the complex and multifactor regulation of microvessels is suggested. PMID- 2579793 TI - [Localization of embryonic prealbumin-1 in the tissues of human malignant tumors]. AB - The distribution of human embryonic prealbumin-1 (EPA-1) has been studied in 52 different malignant tumours using indirect immunofluorescent technique and two types of antibodies to different antigenic determinants: "EPA-1" and "EPA-1S". In mesenchymal tumours (except for desmoids and chondrosarcomas) this glycoproteid was observed in the cytoplasm of tumour cells, but "EPA-1S"--in the connective tissue fibers only. Localization of glycoproteid EPA-1 depends on the type of the used primary antibodies. EPA-1 is also observed in the connective-tissue stroma of most of epithelial tumours. A conclusion is made that transformation of EPA-1 glycoproteid synthesis from definitive to fetal form occurs in malignant tumours. PMID- 2579794 TI - Interelectrode distance and amplitude of the scalp EEG. AB - The relationship between interelectrode distance and amplitude of the scalp EEG was investigated quantitatively, using differential recording arrays extending anteriorly from Oz and coronally from T3. Amplitude was taken as the square root of the power spectrum. For total signal amplitude and for individual frequency bands, measured data correspond well to an exponential function of the form Y = A(1 - e-BX). The inverse of the exponential coefficient B may be taken as a space constant, and the asymptote A as an estimate of absolute EEG amplitude. The concept of the space constant is consistent with current models of neuronal synchrony in the scalp EEG. The coefficients A and B may be useful indices in EEG analysis. PMID- 2579792 TI - [In vitro models for research on cell differentiation and malignant degeneration in the human prostate]. AB - The methods are reviewed for obtaining monolayer epithelium cultures both in normal and hyperplastic or malignant prostate glands. Preparation of pure epithelial tissue cultures is dealt with in detail. The major prostate cell lines are described. Special attention is paid to the markers of differentiation and sensitivity to hormones in normal and tumour prostatic cells in vitro. Prospects for the use of prostatic cell cultures as models in oncology are outlined. PMID- 2579795 TI - Genetic dependence of the electroencephalogram bispectrum. AB - The resting electroencephalogram of monozygotic twins and genetically unrelated controls was analyzed with the ordinary spectrum and with the bispectrum. Both the ordinary spectrum which measures linear EEG wave activity and the bispectrum which detects non-linear and correlated frequency activity had evidence for a genetic basis. It is suggested that there is a genetic basis for the process of EEG generation. PMID- 2579796 TI - [Value of the sleep diary in the study of vigilance dis]. AB - This study presents an easy and practical subjective method for evaluating vigilance disorders: the sleep diary. We used it in hypersomnia and deficits of waking. Sleep diaries were filled in by 10 control and 22 hypersomniac subjects. Twenty-four hour polyhypnographic recording allowed the classification of hypersomnia as 13 narcolepsies, 9 hypersomnias with a prevalence of PS, 2 'harmonious' hypersomnias and 1 waking deficit. The sleep diary data (amount of nocturnal sleep and diurnal sleep onset and vigilance decrease) were compared with polygraphic results. According to the diary data, 3 groups of hypersomnia appeared with regard to the time at which sleep onset occurred. The first group presented an increase of sleep onsets at 2 p.m. In the second group, almost exclusively composed of narcoleptic subjects, sleep onsets occurred every 2 h and in the third group they were distributed throughout the day. These results suggest different physiological mechanisms for these 3 groups of hypersomnia. Finally, the sleep diary seems to be an easy and cheap method of evaluating vigilance disorders in hypersomniac subjects during their everyday life. PMID- 2579797 TI - Abnormal somatosensory evoked potentials in amyotrophic lateral sclerosis. AB - A patient with typical clinical and electromyographic features of amyotrophic lateral sclerosis (ALS) was found to have abnormal somatosensory evoked potentials (SEPs). Evoked responses are generally considered to be normal in ALS despite occasional pathological and clinical evidence of sensory involvement. Thus, abnormal SEPs are considered to argue against a diagnosis of ALS. Based on the present case and a review of the literature, we suggest that abnormal SEPs need not exclude a diagnosis of ALS. PMID- 2579798 TI - Test-retest reliability of spectral parameters of the EEG. AB - The topic of this paper is the intraindividual stability of the EEG at rest for repeated recordings with respect to two sets of spectral parameters. Variability arises due to changes in experimental conditions (such as vigilance) and also due to the inherent random elements of the EEG. The two sets of parameters considered are broad-band parameters and parameters characterizing rhythmic and 'diffuse' activity separately, derived from autoregressive fitting. In spite of some imprecision in the definition of the EEG at rest, satisfactory test-retest correlations were found. They proved to be quite homogeneous topographically, but not across frequency bands: delta power is less reliable and to some extent also beta activity, whereas the alpha bands perform well. The frequency of the alpha rhythm shows a good reliability and, given the difficulties involved with the concept, also the degree of synchronization. The power of rhythmic and of diffuse activity showed more modest retest correlations, probably to be attributed to methodological problems in determining these quantities. On the whole, the results confirm that the normal EEG can be treated as an intraindividually rather stable trait, that artifacts play a minor role in this respect and that 20 sec of activity are sufficient to reduce adequately the variability inherent in the EEG. PMID- 2579799 TI - Nerve impulse propagation along central and peripheral fast conducting motor and sensory pathways in man. AB - Forty-four limbs from 11 healthy volunteers were examined. Spinal and scalp somatosensory evoked potentials to median and peroneal nerve stimulation were recorded and the peripheral (wrist-Erb, Erb-cervical, knee-thoracic spine) and central (cervical-scalp, thoracic-cervical spine, spine-scalp) conduction times and velocities (CTs, CVs) were calculated. Sensory and mixed trunks of median and peroneal nerves were also stimulated and their motor and sensory CVs in mid distal districts were measured. Motor responses to scalp (motor areas for hand and leg muscles) and spinal cord stimulation (cervical and lower thoracic levels) were carried out through skin rectangular plate electrodes delivering high voltage (880-1870 V) brief anodal pulses. The intracranial (scalp-cervical) and intraspinal (cervical-thoracic spine) CTs and CVs of motor pathways were measured. The elbow-cervical and knee-thoracic spines CTs of motor fibres were also calculated through the F wave method, which gave values almost superimposable on those obtained through direct spine stimulation. Nerve propagation was faster in sensory than in motor fibres in peripheral nerve mid distal districts, while this difference was reduced or reversed in more proximal segments, including nerve roots. The scalp-cervical CT was slightly shorter in motor than in sensory fibres after subtraction of synaptic delays (6.12 vs. 6.18 msec). The scalp-lower thoracic spine, as well as the intraspinal, CVs were 7-12% faster in sensory than in motor pathways (45.3 vs. 38.7 m/sec for the former; 62.65 vs. 55.4 m/sec for the latter). The reported method allows the evaluation of fast conducting motor and sensory pathways along 'central' and 'peripheral' nerve structures of the entire body. Preliminary findings on scalp stimulation of brain motor areas with low voltage pulses are also included. PMID- 2579800 TI - Decrement of somatosensory evoked potentials during repetitive stimulation. AB - In normal subjects, cerebral potentials were evoked by brief, passive extension of the wrist joint at various interstimulus intervals (ISIs). The resulting somatosensory evoked potentials (SEPs) were found to decrease during repetitive stimulation. The greatest decrement occurred between the first and second responses of each series. After cessation of stimuli, the SEP amplitude returned to control values over a prolonged, exponential time course. The authors postulate that the observed response decrement may be a form of habituation, which provides a model for studying the neuronal substrates of behavior. PMID- 2579801 TI - Event-related potentials, lexical decision and semantic priming. AB - ERPs were recorded during a lexical decision task in order to investigate electrophysiological concomitants of semantic priming. The stimuli were 240 words and 240 nonwords presented one per trial at a fixed intertrial interval. Subjects were required to classify each stimulus as a word or nonword by pressing one of two response buttons. ERPs were recorded from 14 scalp locations, the right suborbital ridge, and the left earlobe, all referred to a balanced non-cephalic reference. RT and error data confirmed that semantic priming occurred under the conditions employed: primed words (those preceded by a semantically related word) were identified as words faster and more accurately than were unprimed words (those preceded by semantically unrelated words or nonwords). ERPs for all stimulus types were characterized by a large positivity peaking between 550 and 650 msec, preceded by a negative-going deflection peaking at approximately 400 msec. ERPs for primed and unprimed words were shown to differ significantly, diverging 200-250 msec following stimulus onset, reaching a maximum near the peak of the negative-going deflection at 400 msec. These differences were observed at locations over both hemispheres and were maximal in the centroparietal region. Although P300 latency differences between primed and unprimed words were also obtained, the priming effect on ERPs at shorter latencies could not be explained solely by P300 latency effects. Possible relationships between these ERP concomitants of semantic priming and P300, N200, and N400 were discussed. PMID- 2579802 TI - Phencyclidine (PCP): effects of acute and chronic administration on EEG activities in the rhesus monkey. AB - Effects of acute and chronic administration of phencyclidine (PCP) on EEG activities and gross behavior were studied in monkeys with electrodes implanted in the brain. Administration of PCP (2.0 or 4.0 mg/kg i.v.) in monkeys produced a biphasic pattern of inhibition and excitation of behavior during 6-8 h observation period. The inhibitory phase appeared 1-3 min after PCP injection, and was uniquely characterized by high-voltage slow waves with delta waves (0.6 0.8 c/sec) in the parietal lobe and by those with theta waves (4-5 c/sec) in the occipital lobe and hippocampus during behavioral stupor. This inhibitory phase lasted 1-1.5 h, and subsequently, high-voltage fast wave with enhancement of theta waves and nystagmus appeared during behavioral arousal. Upon chronic PCP administration, the intensity and duration of the inhibitory phase progressively decreased, while the effects of the excitatory phase increased. The results suggest that PCP administration in monkeys produces a biphasic pattern of inhibitory and excitatory effects and upon chronic administration a tolerance develops to the inhibitory effect while an augmentation of the excitatory effect develops. PMID- 2579803 TI - Effects of 2-amino-7-phosphonoheptanoic acid on EEG of rats. AB - 2-APH is an antagonist of excitation due to dicarboxylic amino acids and has a protective effect against several types of experimental seizures. We have studied its effect on EEG of rats. Following either intracerebroventricular or intraperitoneal administration of 2-APH produces slow waves of high voltage in central cortex. The anticonvulsant action of this drug may be related to altered activity in neurones of this area. PMID- 2579804 TI - Antiidiotypic antibodies as probes for receptor structure and function. PMID- 2579805 TI - Root growth of Cynodon dactylon and Eleusine indica collected from motorways at different concentrations of lead. AB - An ecological survey was conducted on the roadside vegetation at three different sites: Tai Po, a commercial and residential area (average annual daily traffic (AADT) = 23730; and Shek O and Wu Kai Sha, recreational areas (AADT = 1590 and 20, respectively). Cynodon dactylon and Eleusine indica were the two most dominant species recorded. The Tai Po site had higher Pb contents in both soil and plant, followed by Shek O, and then Wu Kai Sha. Tillers of C. dactylon and E. indica from the three sites were subjected to a series concentrations of Pb(NO3)2. By comparing their indexes of tolerance and values of 14-day EC50 (effective concentration reducing the normal root growth by 50%), roadside populations of the two grasses collected from Tai Po and Shek O, especially the former one, were more tolerant to elevated levels of Pb compared with those collected from Wu Kai Sha. PMID- 2579806 TI - The response of rat alveolar macrophages to chronic inhalation of coal dust and/or diesel exhaust. AB - The use of diesel-powered equipment in underground mines has raised questions regarding possible synergistic effects of coal dust and diesel emissions. Therefore, the effects of chronic exposure of rats to coal dust and/or diesel exhaust on various properties of alveolar macrophages were investigated. Inhalation exposure of rats was 7 hr/day, 5 days/week for 2 years. Exposure groups were: filtered air controls, 2 mg/m3 coal dust, 2 mg/m3 diesel particulate, and 1 mg/m3 coal dust plus 1 mg/m3 diesel exhaust. Exposure to coal dust and/or diesel exhaust had little effect on oxygen consumption, membrane integrity, lysosomal enzyme activity, or protein content of alveolar macrophages. However, exposure to coal dust increased macrophage yield, enhanced chemiluminescence, and increased the activity of the cell membrane (i.e., increased cellular spreading and surface ruffling). In contrast, diesel emissions depressed chemiluminescence and decreased the ruffling of the cell membrane. Therefore, the data suggest that exposure to coal dust and/or diesel exhaust does not affect the viability of alveolar macrophages. However, coal dust may activate alveolar macrophages while diesel emissions may depress the phagocytic activity of these cells. The combination of exposures to coal dust and diesel exhaust results in a phagocytic activity which is an average of the effects of separate exposures. PMID- 2579807 TI - More about substance P. PMID- 2579808 TI - Distribution of substance P-like immunoreactivity in the enteric neurons of the large colon of normal and amitraz-treated ponies: an immunocytochemical study. AB - The distribution of the putative motor excitatory neurotransmitter, substance P, was studied immunocytochemically in the left dorsal colon of four normal control ponies and three ponies with amitraz-induced impaction colic. Substance P-like immunoreactivity in the control ponies was observed in nerve fibres in all layers of the bowel wall and in the nerve cell bodies of the enteric ganglia. The substance P-like immunoreactivity was clearly more intense in the cell bodies of submucosal ganglia than in those of the myenteric ganglia. The internodal nerve strands of the myenteric plexus were very rich in substance P-like immunoreactivity and within the ganglia they formed dense varicose networks around the neuronal cell bodies. Nerve bundles rich in substance P-like immunoreactivity diverged inward from the myenteric plexus to contribute an abundance of varicose immunoreactive fibres to the circular muscle of the tunica muscularis. Nerve fascicles with substance P-like immunoreactivity were sparse in the longitudinal muscle except in the thickened taenial band. In the submucosa many of the nerve fibres with substance P-like immunoreactivity appeared to arise from ganglionic cell bodies. Immunoreactive fibres commonly condensed around arterial vessels in the submucosa. Fine immunoreactive nerve fascicles from the submucosal plexus also projected internally to supply the muscularis mucosae and form periglandular arrays in the lamina propria. The distribution of substance P like immunoreactivity in the normal equine colon differed in some respects from patterns observed in large intestines of other mammals. When the colons of normal and amitraz-treated ponies were compared no differences were discerned in the distribution or intensity of substance P-like reactivity. PMID- 2579810 TI - Conserved unpaired adenine residues are important for ordered structures of 5S ribosomal RNA. An infrared study of the secondary and tertiary structure of Thermus thermophilus 5S rRNA. AB - An improved set of infrared calibration spectra for the determination of G X C and A X U base pairs leads to 32 +/- 3 G X C (+ G X U) and 4 +/- 1 A X U base pairs for Thermus thermophilus 5S RNA in the presence and absence of Mg2+. These results give further support for the consensus secondary structure of 5S RNA recently proposed by several groups. T. thermophilus 5S RNA shows, in the presence of Mg2+, a distinct two-step thermal melting of its ordered structure. Based on new data about the stacking dependence of infrared intensities of unpaired ribonucleotides the spectral changes of the low-temperature transition should be explained by melting of stacked arrangements of unpaired bases and/or non-standard base pairs. Striking is the reduction in A stacking, which is not related to the melting of A X U base pairs, indicating the importance of the mostly conserved unpaired adenines for the Mg2+ stabilized higher-order structures especially within internal loops of 5S RNA. PMID- 2579809 TI - Covalent labeling of functional states of the acetylcholine receptor. Effects of antagonists on the receptor conformation. AB - Photoaffinity labeling of membrane-bound nicotinic acetylcholine receptor from Torpedo marmorata electric tissue with the ion-channel blocker [3H]TPMP+ reveals various functional states of the receptor protein if labeling is performed with ms time resolution. In the resting and in the activated state most of the label is incorporated into the alpha-polypeptide chains of the receptor complex. When equilibrated with agonists and antagonists, predominantly the delta-polypeptide chain (and to a lesser extent the beta-chain) reacts with the photolabel. Reactivity of the delta-chain increases after exposure to cholinergic effectors with a half-life slower than the kinetics of receptor activation or rapid desensitization. Agonists and antagonists stimulate photolabelling of the delta chain with different kinetics. For acetylcholine, carbamoylcholine and suberyldicholine the half-life of the reactivity increases is 400 - 500 ms; for the antagonists hexamethonium, d-tubocurarine and flaxedil it is about 10 s. The latter slow kinetics are also observed when the receptor is preequilibrated with agonists or antagonists prior to mixing with [3H]TPMP+ and starting the photoreaction. We conclude that time-resolved photoaffinity labeling can convalently mark protein structures involved in receptor functions. Of special interest is the observation that antagonists also induce a conformational change in the receptor protein. PMID- 2579811 TI - Regulation of hamster carbamoyl-phosphate synthase II by 5-phospho-alpha-D ribosyl 1-diphosphate and uridine 5'-triphosphate. AB - In mammals, carbamoyl phosphate for utilization in pyrimidine biosynthesis is synthesized by a glutamine-dependent carbamoyl-phosphate synthase II which is subject to regulation by 5-phospho-alpha-D-ribosyl 1-diphosphate (PRib-PP), a positive effector, and MgUTP, a negative effector [Mori, M., Ishida, H. and Tatibana, M. (1975) Biochemistry 14, 2622-2630]. We have found that Lineweaver Burk plots of carbamoyl phosphate synthase activity versus 1/[MgATP] are described by a velocity equation which is a ratio of quadratic polynomials, consistent with a positive homotropic interaction between two catalytic sites for the binding of MgATP (Ks = 16.6 +/- 3.1 mM, interaction factor a = 0.00538 +/- 0.00245). The activating effect of PRib-PP upon carbamoyl-phosphate synthase is consistent with PRib-PP binding at an allosteric site (Ka = 31.4 +/- 6.4 microM) and promoting the binding of a first molecule of MgATP as substrate (interaction factor l = 0.0437 +/- 0.0063). Thus MgATP and PRib-PP bind to the E X MgATP complex with respective dissociation constants of a X Ks = 0.089 mM and l X Ka = 1.4 microM while MgATP binds to the E X PRib-PP complex with a dissociation constant of l X Ks = 0.73 mM. Data for the inhibitory effect of MgUTP upon carbamoyl-phosphate synthase indicate that MgUTP competes with MgATP for binding at the catalytic site (Ki = 0.203 +/- 0.016 mM). A computer model has recently been developed which enables quantitative stimulation of the time-dependent effects of blockade of the pyrimidine pathway by a tight-binding enzyme inhibitor [Duggleby, R.G. and Christopherson, R.I. (1984) Eur. J. Biochem. 143, 221-226]. The velocity equation derived in the present paper provides a quantitative basis for predicting changes in the flux through the de novo pyrimidine pathway in growing cells. PMID- 2579812 TI - Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities. AB - The recently chemically synthesized Escherichia coli lipid A and the natural free lipid A of E. coli were compared with respect to their endotoxic activities in the following test systems: lethal toxicity, pyrogenicity, local Shwartzman reactivity, Limulus amoebocyte lysate gelation capacity, tumour necrotizing activity, B cell mitogenicity, induction of prostaglandin synthesis in macrophages, and antigenic specificity. It was found that synthetic and natural free lipid A exhibit identical activities and are indistinguishable in all tests. PMID- 2579813 TI - Effect of avian osteopetrosis virus infection on cells and their collagen synthesis in vitro. AB - Primary avian tendon fibroblasts and calvarial osteoblasts were infected with the avian osteopetrosis virus MAV.2-O, in vitro. The infected tendon cells could be cloned in soft agar and kept in culture for at least 25 passages, a number not reached by uncloned infected cells. In contrast to many other virus-transformed fibroblasts, these cells continued making collagen and fibronectin, and there were no gross morphological changes as observed in the light microscope. Changes were seen in their cytoskeletal structure, however, as observed by immunofluorescence. The cloned cells were not tumorigenic in nude mice, nor had they an altered pattern of protein phosphorylation. MAV.2-O-infected fibroblasts and the cloned cells synthesized 2-3 times more collagen type I, the main product of their biosynthetic machinery, than control cells. The proportion of the total cellular RNA consisting of specific mRNAs for the precursor of collagen, procollagen pro-alpha 1 and pro-alpha 2 chains, was higher in the infected cells than in normal fibroblasts. Southern blotting experiments indicated that there was no rearrangement of the collagen genes after infection with this virus. Furthermore, large viral DNA fragments were not integrated into the immediate vicinity of the 5' end of the alpha 2-collagen gene. PMID- 2579814 TI - Synchronous exocytosis in Paramecium cells. IV. Polyamino compounds as potent trigger agents for repeatable trigger-redocking cycles. AB - We found that different polyamino compounds trigger the instantaneous and simultaneous release of trichocysts from Paramecium tetraurelia cells (monoxenically bacterized cultures), provided amino groups are spaced in intervals of approximately 1.0 nm; in this case even diamines or oligopeptides exert some trigger effect. The most potent trigger agent found was aminoethyldextran (AED, MW = 40 kDa) which was used mainly as a derivative with 40 -NH2/molecule. A maximal response (strain K401) was achieved at 1.38 X 10(-6) M, a half maximal response at 1.08 X 10(-6) M. AED acts by a dual effect, i.e., not only by statistically properly spaced amino groups but also by some additional effect of the dextran molecule, since this greatly enhances the effect of oligoamines, although it exerts no trigger effect per se. From a total of approximately 1120 or approximately 1230 trichocysts per cell (strain K401 or 7S) approximately 95% are releasable by AED. In these strains the number of non releasable trichocysts corresponds closely to the number of undocked trichocysts floating in the cytoplasm, so that practically all trichocysts which are docked to the cell membrane, can be released. (We also analysed different mutant strains for their response to AED.) Massive trichocyst release does not impair cell viability or culture growth, and multiple release-redocking cycles can be performed; up to 5 trigger-docking cycles were tested with individual cells in 12 h intervals. AED-triggered exocytosis requires a free extracellular [Ca2+] of greater than or equal to 10(-5) M; it is inhibited by EGTA (ethyleneglycol bis(beta-aminoethyl ether)-N,N'-tetraacetate), by a short pH 5.5 shock or by neomycin at 10(-5) M concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579815 TI - Immunofluorescent localisation of cytokeratin antigens in mitotic HeLa cells using monoclonal antibodies. AB - The organisation of cytokeratin filaments in mitotic HeLa cells has been analysed by immunofluorescence microscopy using a monoclonal antibody which recognises proteins with apparent subunit molecular weights of 52 kDa and 57 kDa and which binds exclusively to cytokeratin-type filaments. Mitotic cells were prepared for microscopic analysis by hypotonic swelling, centrifugation onto glass slides, brief pre-extraction with 0.1% Triton X-100 and fixation in 80% ethanol. This procedure gave particularly good resolution of intermediate filaments and preservation of chromosome morphology. In prometaphase-metaphase cells the antigen was present in an anastomosing filament network which completely or partially enclosed the chromosomes, in filament fragments and in cytoplasmic aggregates. The epichromosomal filament network was absent from cells in anaphase or later stages of mitosis. In these cells non-filamentous antigen was often located in a narrow band defining the periphery of individual chromosomes and in variable numbers of cytoplasmic filaments or fragments. The results suggest that extensive disaggregation and reformation of cytokeratin filaments occurs during mitosis and that disaggregated cytokeratin proteins are frequently located adjacent to mitotic chromosomes. PMID- 2579816 TI - Positive 57Co-bleomycin scintigraphy in silent mediastinal metastases of malignant melanoma. AB - A case with an intense accumulation of 57Co-bleomycin in lymph node metastases of malignant melanoma in the mediastinum as a casual finding is reported. The patient had undergone a 57Co-bleomycin scintigraphy because of a peripheral lesion on the chest X-ray, in which a pathological diagnosis was impossible to obtain. This lesion showed no uptake of the radiopharmaceutical. PMID- 2579817 TI - Local immunoglobulin synthesis and blood-brain barrier assessment in subacute sclerosing panencephalitis. AB - The immunoglobulin synthesis within the central nervous system and the blood brain barrier (BBB) function were evaluated in 6 patients with subacute sclerosing panencephalitis (SSPE) using the IgG index and a graphic method based on serum/CSF albumin, alpha 2-macroglobulin, and IgG quotients. A strong local production of IgG was documented by both methods in all 6 cases of SSPE. Concerning the graphic analysis, the decrease in the serum/CSF alpha 2 macroglobulin ratio disclosed BBB dysfunction in 2 cases of SSPE, suggesting, in the absence of the serum/CSF albumin quotient abnormalities, that a homeostatic mechanism for CSF proteins can cause changes in the CSF protein profile. PMID- 2579818 TI - Prognostic value of computed tomography in aphasic stroke patients. AB - In order to evaluate the prognostic value of CT scan in aphasic stroke patients, a prospective study was performed during the first 3 months of the disease. The severity of the language disorders was assessed by means of a quantitative method. In cortico-subcortical lesions, the verbal expression recovery rate and the final verbal expression and comprehension status depended on the infarct size. No relation was observed between the latter and the verbal comprehension recovery rate. In deep-seated lesions, computed tomography provided no information concerning the prognosis. PMID- 2579819 TI - Atypical phenotype of Refsum's disease: clinical, biochemical, neurophysiological and pathological study. AB - The authors describe the clinical, biochemical, electrophysiological and ultrastructural study of a case of Refsum's disease whose phenotype suggested other hereditary ataxias. Due to the presence of Babinski sign and optic atrophy and the absence of retinitis pigmentosa, this case can be considered atypical. Electrophysiological and ultrastructural findings confirm the variability of peripheral lesions in this hereditary polyneuropathy. PMID- 2579820 TI - Indole amines and amino acids in various brain regions after infusion of branched chain amino acids into hepatectomized rats. AB - This study was designed to determine regional changes of amino acids and indole amines in the brain and possible interactions between amino acids and indole amines 18 h after hepatectomy in rats. Hepatectomy and glucose infusion alone resulted in a profound increase of most large neutral amino acids (LNAA) in plasma and in the brain except for the branched-chain amino acids (BCAA), which maintained normal or somewhat lower values in plasma. Hepatectomy and infusion of glucose combined with BCAA sharply reduced the plasma and brain amino acid concentrations of other LNAA. Simultaneously the concentrations of serotonin and 5-hydroxyindoleacetic acid were decreased in all brain regions. In both groups of hepatectomized rats there were regional variations of the amino acid and the indole amine concentrations in the brain, but the response to BCAA infusion was generally the same in all brain regions. No difference in survival between the 2 groups could be found. PMID- 2579821 TI - Inhibition of hapten-specific cytotoxic T cell recognition by monoclonal anti hapten antibodies. AB - The T cell-mediated cytotoxic response against autologous cells modified with the sulfhydryl reagent I-AED (N-iodoacetyl-N'-(5-sulfonic-1-naphthyl) ethylene diamine) is hapten specific and H-2 restricted (Levy, R. B., Shearer, G. M., Richardson, J. C. and Henkart, P. A., J. Immunol. 1981. 127: 523). We have produced a monoclonal antibody (V-6-3, IgM) which binds to AED-modified cells and proteins. Competition experiments by free hapten indicated that the binding was AED specific. The effect of the mAb on AED-specific cytotoxic T cell recognition at the effector and induction stage has been examined. Anti-AED mAb inhibited the cell-mediated lysis of some but not all AED-specific, H-2b-restricted long-term cytotoxic T cell clones and of bulk-cultured C57BL/6 anti-AED-self effector cells. This blocking was not due to nonspecific agglutination of targets since lysis of AED-modified target cells by alloreactive effector cells was not affected by this mAb under comparable conditions. Furthermore anti-AED mAb specifically inhibited the antigen-induced proliferation of AED-specific long term cytotoxic T cell clones and the generation of AED-specific cytotoxic effector cells in secondary cultures. This monoclonal anti-AED antibody bound to cells modified by the recently described aminoreactive reagent AED-NH2 (Takai, Y., Mizuochi, H., Fujiwava, H. and Hamaoka, T., J. Immunol. 1984. 132: 57); these same target cells were, however, not lysed by AED-SH-specific cytotoxic T cell clones. PMID- 2579822 TI - Various expressions of a unique anti-human thyroglobulin antibody repertoire in normal state and autoimmune disease. AB - Polyclonal anti-human thyroglobulin (hTgb) antibodies (Ab) were purified from sera of rabbits immunized with human thyroglobulin, normal humans and patients suffering from Graves' disease, Hashimoto's thyroiditis and thyroid carcinoma. The avidity of the various Ab preparations for hTgb ranged from 0.3 X 10(10) -2.2 X 10(10) M-1. By using well characterized mouse monoclonal antibodies (mAb) directed against hTgb, it was shown that the fine specificities of induced anti hTgb Ab in rabbits, natural Ab in normal subjects and autoantibodies in diseased patients were similar; however, they differed from that of rabbit anti-bovine and anti-porcine thyroglobulin Ab which were able to inhibit the hTgb binding of only a few of the mAb. Anti-hTgb in rabbits and in patients with thyroid carcinoma varied from those in normal subjects only by uniformly elevated serum titers. In contrast, patients with Graves' disease and Hashimoto's thyroiditis showed an increased concentration essentially restricted to Ab reacting with few of the antigenic determinants recognized by the mAb. Our data suggest that the repertoire of anti-hTgb Ab is similar in mouse, rabbit and human. Furthermore, the finding of identical fine specificities for anti-hTgb Ab in normal and pathological conditions implies that autoantibodies are produced in normal subjects and held to a low level by regulatory processes which fail with respect to selected epitopes in autoimmune diseases. PMID- 2579823 TI - T helper cell recognition of idiotopes on lambda 2 light chains of M315 and T952: evidence for dependence on somatic mutations in the third hypervariable region. AB - Previous work has indicated that BALB/c T helper cells (Th) recognize an idiotope expressed on a 88-114/117 fragment of V lambda 2 of BALB/c myeloma protein 315. In the present study the antigenic structure of this idiotope was further analyzed. Conventional carrier-specific Th elicited by immunization of BALB/c mice with free lambda 2(315) did not cross-react with the free lambda 2 chain of the BALB/c myeloma protein T952 which differs from lambda 2(315) in five amino acid positions (38, 94, 95, 96, 99). Similarly, Th primed with free lambda 2T952 did not respond to a boost with free lambda 2(315). Thus, BALB/c lambda 2(315) specific Th recognize an idiotope that depends on some or all of the residues at positions 94, 95, 96 and 99. Furthermore, free lambda 2T952 contains an idiotope immunogenic to Th that depends on some or all of residues 38, 94, 95, 96 and 99. Th recognition of the free lambda 2T952 idiotope was quenched upon H + L chain assembly because Th elicited by free lambda 2T952 did not respond to a boost with the complete T952 myeloma protein. In contrast to the lack of Th cell cross reactivity, some of the antisera from BALB/c mice immunized with free lambda 2T952 cross-reacted with free lambda 2(315), free lambda lJ558 and free lambda 3CBPC49 but not with free kappa W3129 or polyclonal L chains. The H chain of T952 (alpha, kappa 2) myeloma protein was abnormally short (Mr = 48 000) and T952 existed as a halfmere probably due to this H chain deletion. Furthermore, H and L chains were disulfide bonded to each other. PMID- 2579824 TI - Structural invariance of T4 molecules from T cell clones of different antigen and major histocompatibility complex specificities. AB - Recent studies have suggested that the T4 molecule may bind to class II major histocompatibility complex (MHC) gene products on target cells. Such an interaction could be with either a polymorphic or monomorphic determinant on class II MHC genes. The first would imply that T4 is structurally variable and represents a component of a dual receptor, whereas the latter would suggest that T4 is structurally invariant and serves as an accessory binding molecule. To resolve this question we studied the structural variability of T4 molecules isolated from four clones of differing antigen/MHC specificities. By one- and two dimensional electrophoretic analysis and by peptide mapping, we detected no differences among the 55-kDa T4 molecules from these clones. We conclude that T4 serves as an invariant accessory binding structure and that T4 does not confer MHC specificity on T cells. PMID- 2579826 TI - In vitro characterization of the alpha-adrenoceptors in human prostate. AB - The alpha-adrenoceptors of the human prostate gland were characterized in vitro by the use of antagonists selective for alpha 1- and alpha 2-adrenoceptor subtypes. The contractile response induced by norepinephrine in this tissue could be antagonized by prazosin, a selective alpha 1-antagonist, with a receptor dissociation constant (KB) of 4.0 +/- 0.9 nM. The selective alpha 2-antagonists rauwolscine and SK&F 86466 were less potent antagonists of this response, with KB values of 1020 +/- 400 nM and 2400 +/- 800 nM, respectively. The irreversible alpha-antagonists benextramine and phenoxybenzamine, both of which preferentially inactivate the alpha 1-subtype, produced marked depression of norepinephrine induced contraction. These data would suggest that the alpha-receptors on prostatic smooth muscle are predominantly of the alpha 1-subtype. PMID- 2579825 TI - Mapping cell surface antigens on mouse pre-B cell lines. AB - Characterization of cell surface molecules expressed by B cell precursors has been hampered by the inability to routinely assay such cells from freshly explanted normal lymphoid tissues. However, a large number of transformed pre-B cell clones have been isolated which presumably include those precursors recently entering the B cell lineage (obtained from fetal liver and more rarely from adult bone marrow) and extending to those clones which are poised to become surface Ig positive B cells. In this report, we have quantitated expression of 10 different cell surface molecules, 5 of which bear special interest as B cell differentiation antigens, among a large panel of pre-B cell clones. PMID- 2579827 TI - Effects of neurotensin on the isolated mouse distal colon. AB - The effects of neurotensin were studied in the isolated mouse distal colon. This peptide had potent stimulatory effects which were of pre- or postjunctional origin according to the concentrations used. At low concentrations (10(-11)-10( 10) M) neurotensin induced neurogenic non-cholinergic contractions which seemed to result from the release of substance P (or substance P-like activity) by enteric excitatory nerves. At higher concentrations (10(-9)-10(-7) M) neurotensin elicited a biphasic effect consisting of transient relaxation rapidly followed by myogenic contraction. The bee venom toxin apamin inhibited the NT-induced relaxation while inhibition of prostaglandin synthesis by indomethacin abolished the contraction phase. All these responses were tightly related to the extracellular Ca2+ concentration. These properties of neurotensin point to a possible role for this peptide as a modulator of colonic motility. PMID- 2579829 TI - Inhibition of IgE-mediated mast cell degranulation by sulphasalazine. AB - The effect of sulphasalazine on two mast cell populations and human peripheral leukocytes is reported. Sulphasalazine inhibited histamine release from mouse and rat mast cells, but it caused a potentiation of secretion in human peripheral leukocytes. The drug alone did not induce histamine release when administered without an anaphylactic stimulus. The results are discussed in terms of a possible mode of action of sulphasalazine in the treatment of inflammatory bowel disease. PMID- 2579828 TI - Stimulation frequency alters the inotropic response of atrial muscle to BAY K 8644. AB - The inotropic and chronotropic effects of BAY K-8644 were examined in isolated guinea pig atria. The compound increased both rate and contractile force. Sensitivity to the inotropic effect was enhanced by increasing stimulation frequency between 0.5 and 3.3 Hz. The maximum developed tension elicited by the agent was reduced at 3.3 Hz. At BAY K-8644 concentrations up of to 3 X 10(-5) M, no dysrhythmic effects or other toxic signs such as an increase in resting tension were observed. These results are consistent with the suggestion that BAY K-8644 acts as a partial 'calcium agonist'. PMID- 2579830 TI - In vitro inhibition of allergic histamine release by calcium antagonists. AB - The ability of calcium entry blockers to inhibit allergic histamine release from rabbit leukocytes was studied. Bepridil, verapamil, nifedipine, diltiazem and TMB 8 produced concentration-dependent inhibition of allergic histamine release from rabbit leukocytes. The calculated IC50s (microM) were as follows: verapamil = 1.3; bepridil = 2.3; TMB-8 = 3.0; nifedipine = 3.3; and diltiazem = 5.3. Verapamil also exerted concentration-dependent inhibition of allergic histamine release from human basophils with an IC50 of 3.7 microM. These agents may act by interfering with the influx of Ca2+ into the leukocytes as well as calcium dependent steps (e.g., activation of calmodulin, phospholipase A2 and/or 5 lipoxygenase etc.) in the process of histamine secretion. PMID- 2579831 TI - Effect of imipramine on calcium and potassium currents in isolated bovine ventricular myocytes. AB - Isolated bovine ventricular myocytes were investigated with a two-microelectrode voltage clamp technique. The clamp currents were analyzed in terms of ICa and IK. Possible effects on INa were avoided by superfusing the cells with a Na-free medium. Imipramine (IMI) was applied at a concentration of 3.6 microM. Within the initial 3 min (early phase), IMI reduced peak ICa by 38 +/- 9% but IMI did not change the time constants of inactivation, the voltage dependence of peak ICa or its reversal potential. Therefore, we conclude that IMI reduced calcium conductance. After 10 min of exposure (late phase), IMI can also reduce the reversal potential of ICa. The inward rectifying potassium current (IK1) was transiently enhanced by 15 +/- 8% but later (8-10 min) reduced by 19 +/- 4%. Washout of IMI completely reversed all the effects within 10 min. Reduction of ICa diminished the rate of rise and the overshoot of the slow action potential and can explain the shortening of the AP seen in both Na-free and Na-containing media. Possible clinical implications are discussed. PMID- 2579832 TI - A monoclonal antibody recognizing cytoskeletal keratins of stratified epithelia and bladder carcinomas. AB - Monoclonal antibodies were generated by immunizing rats with mouse bladder carcinomas, fusing their spleen cells with NS-1 myeloma cells and selecting for antibodies that bound to mouse bladder carcinomas. One of the antibodies, IG5, recognizes an antigenic determinant which is present in mouse bladder carcinoma cytoskeletons and is not detectable in the normal bladder epithelium. Indirect immunofluorescence studies revealed that the antigen is expressed intracellularly and is organized in the form of filamentous arrays. The antigen was detected by peroxidase--antiperoxidase immunocytochemistry in stratified epithelia and glands derived from these, but has not been observed in any tissues of mesenchymal or neuronal origin. Various normal and neoplastic human tissues were subsequently tested for reactivity with antibody IG5. Antigen expression in normal tissues was similar to that in the mouse. Most carcinomas of the bladder and lung were stained, while all of eleven colon carcinomas were negative. Antibody IG5 immunoprecipitated radio-iodinated peptides of 58, 56, 52 and 43 kD molecular weight from mouse bladder carcinomas. Western blotting experiments with antibody IG5 demonstrated bands of 56 and 50 kD in a keratin-enriched fraction of the bladder carcinoma cytoskeleton. Antibody IG5 reacted with molecules which have several properties typical of cytoskeletal keratin peptides. Our findings are discussed in the context of previously described keratin peptides and relevant monoclonal antibodies. PMID- 2579833 TI - Reverse differential staining of sister chromatids induced by Hoechst plus black light and endonuclease. AB - A differential Giemsa staining between sister chromatids was obtained by treating chromosomes replicated twice in medium containing 5-bromodeoxyuridine (BrdU) with Hoechst 33258 plus black light at 55 degrees C (HB pretreatment) and deoxyribonuclease (DNase) I, II, or micrococcal nuclease. In this staining pattern the BrdU bifilarly substituted chromatids were darkly and the unifilarly substituted chromatids lightly stained. This staining pattern was obtained only by staining the HB-DNase I-treated chromosomes with Giemsa and methylene blue, not by several other dyes tested. Relatively more DNA labelling was removed from the non-BrdU-substituted than the BrdU-substituted chromosomes, when the HB pretreated chromosomes were digested with DNase I. But the protein labelling was not removed appreciably in the same treatment. The differential DNase I sensitivity between the non-BrdU-substituted and BrdU-substituted chromosomes disappeared when the HB-pretreated chromosomes were incubated with proteinase K before The DNase I digestion. Moreover, no differential DNase I sensitivity was found between the HB-pretreated isolated DNA containing and not containing BrdU. We propose that during the HB pretreatment, more DNA-protein cross-linkings are induced in BrdU bifilarly substituted than the unifilarly substituted chromatids. This structure protects the chromosomal DNA against the DNase I digestion. Thus, a reverse differential Giemsa staining between sister chromatids is obtained by the HB-DNase I treatment. PMID- 2579834 TI - Co-localization of non-histone protein BA with U-snRNPs to the same regions of the cell nucleus. AB - Using indirect immunofluorescence, nuclear non-histone protein BA was localized in a normal rat liver cell line. Protein BA antibodies immunostained nuclear structures producing a speckled immunofluorescent staining pattern. Nuclear structures stained with protein BA antibodies were sensitive to DNase I digestion, but not to RNase. The speckled pattern of nuclear fluorescence observed with protein BA antibodies was similar to that reported earlier for Sm antibodies, which react with U-snRNPs. Using double-label indirect immunofluorescence, the Sm antigen was shown to be concentrated in the same regions of the nucleus which contain protein BA. Immunoblot analysis of total nuclear proteins with the two antibodies demonstrated that protein BA and the major Sm antigen have similar molecular weights, but are antigenically distinct. In addition, they differ in their extractabilities from the cell nucleus. PMID- 2579835 TI - In vitro activation of human sperm induced by amphibian egg extract. AB - In this paper we characterize a system for the activation of human sperm using cell-free extracts from Xenopus laevis eggs. We characterize the kinetics of sperm activation in terms of morphological and DNA synthetic parameters. We have optimized some of the components which are necessary for chromatin decondensation and present data to demonstrate that the in vitro process is efficient over a wide range of salt concentrations and amounts of supplementary reducing agents. PMID- 2579836 TI - Dynamic aspects of cytoplasmic poly(A)+ RNA of Tetrahymena pyriformis. AB - In the present work a study was made of the compartmentalization of the poly(A)+ RNA populations during the cultural development of cells of T. pyriformis that were pre-starved or derived from stationary cultures. It was found that the poly(A)+ RNA content increases when the cells change from stationary to lag phase. The increase in RNA poly(A)+ is manifested exclusively in the polysome compartment. The level of poly(A)+ RNA in the cytoplasmic non-polysomal compartment does not change. The increase in poly(A)+ RNA is concomitant with an expansion of the polysomes. Pre-starved cells initiate polysome formation soon after being transferred to a growing medium. During this time the poly(A)+ RNA content of the non-polysomal compartment decreases and that of polysomes increases in close proportion. Not only in the starved but also in stationary cells and in those that are beginning to grow, the proportion of poly(A)+ RNA in mRNP is higher than in the polysomes. These data are interpreted as indicating that cells of T. pyriformis, derived from stationary cultures are dependent on RNA synthesis for polysome formation; on the other hand, pre-starved cells use preformed non-polysomal poly(A)+ RNA for the same purpose, in the beginning of the cultural development. PMID- 2579837 TI - Cell density and cell shape-related regulation of vimentin and cytokeratin synthesis. Inhibition of vimentin synthesis and appearance of a new 45 kD cytokeratin in dense epithelial cell cultures. AB - The pattern of the intermediate type filament protein synthesis was examined in cultured bovine mammary gland epithelial (BMGE) cells under conditions of varied cell shape and cell-cell contact. In dense monolayer and suspension cultures BMGE cells expressed a new cytokeratin of 45 kD identified as a member of the acidic subfamily of cytokeratins. This polypeptide has a phosphorylated component and is dissociated from the cytokeratins complex in the presence of 6.5 M urea. The mRNA of the new cytokeratin accumulated in dense cell cultures, as revealed by in vitro translation in a cell-free system. In BMGE-H cells that express also vimentin, the synthesis of vimentin decreased dramatically in dense cell cultures, while the synthesis of the 45 kD cytokeratin was maximal under these conditions. The results suggest that the expression of certain cytokeratins and that of vimentin can be coordinately regulated by factors in the cellular environment that effect cell shape and cell surface contacts. PMID- 2579838 TI - Localization of keratin in the cells of the cornea in aphakia and normal mouse embryos. AB - Abnormal lens morphogenesis in the aphakia mutant in the mouse often results in a club-shaped elongated 'lens' that remains attached to the surface epithelium by a persistent connecting stalk, which is partially solid and partially cystic. Usually, the cells are continuous with the surface epithelium of the cornea and also with the cuboidal cells lining the corneal inner surface. Immunofluorescence with keratin antiserum not only gave positive reactions with the corneal epithelial cells, but also with many cells of the lens stalk, including its cysts, and with islands of cells on the inside of the cornea. These keratin containing 'endothelial' cells may be the product of metaplasia of the endothelium into epithelium-like cells. Alternatively, they may also be the result of abnormal migration of epithelial cells into the eye or of abnormal differentiation of neural crest cells. PMID- 2579839 TI - Lenticular energy metabolism during exogenous calcium deprivation and during recovery: effects of dextran-40. AB - Phosphatic metabolites of the intact rabbit lens were quantitated as a function of time by phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy during in vitro incubations at 37 degrees C in calcium-sufficient and calcium deficient modified Earle's buffer with and without the osmotic agent, Dextran-40. Intralenticular pH was determined from the resonance shift position of inorganic orthophosphate (Pi). Incubation of lenses in calcium-deficient buffer resulted in a pronounced, time-dependent decrease in lenticular adenosine triphosphate (ATP) levels. The half-life of ATP within the lens was 11 hr under these experimental conditions. A concomitant, essentially stoichiometric increase in adenosine diphosphate and Pi levels was observed also. The other phosphatic metabolites were unaffected by exogenous calcium deprivation except for adenosine and inosine monophosphate which accumulated with time. Dextran-40 (6%), which has been shown to prevent lens swelling under these same experimental conditions, did not influence the metabolic responses of the lens to external calcium deprivation and did not facilitate subsequent restoration of lens phosphatic metabolites following restoration of a physiologic calcium concentration to the supporting medium. The Dextran-40 did, however, promote the retention of intralenticular pH environment during the experimental period. These findings suggest that the previously reported Dextran-40-dependent recovery of intralenticular sodium and potassium concentrations to control levels following 10 hr of incubation in calcium-deficient media cannot be attributed to a direct energy-sparing action of Dextran-40 on lenticular energy metabolism. Instead, the mechanistic basis for the action of Dextran-40 would appear to be related to its colloid osmotic properties and its ability to prevent lenticular swelling, which otherwise occurs in the absence of Dextran under these experimental conditions. PMID- 2579840 TI - Occupational lung disease following long-term inhalation of pancreatic extracts. AB - Fourteen employees of a pharmaceutical company, who had been exposed to porcine pancreatic and other organic dusts for 1-18 years were examined because of exercise dyspnea and asthmatic attacks. Airway obstruction or bronchial hyperreactivity and disturbance of oxygen diffusion were present in all cases. Two patients showed evidence of acute alveolitis and 3 had radiological signs of mild fibrosis, whilst emphysema dominated in 7 others. Skin tests and bronchial provocation revealed hyperreactivity to pancreatic extracts. Pancreatic alpha amylase was determined as a causative allergen for Type I allergy symptoms by means of RAST. Three pathomechanisms of the lung diseases are discussed: 1) Type I allergy of the airways to pancreatic enzymes, 2) broncho-alveolar Type III reaction to porcine proteins; and 3) proteolytic damage of the lung tissue and an increase of non-specific bronchial reactivity. PMID- 2579841 TI - Platelet hyperfunction in patients with chronic airways obstruction. AB - Platelet aggregation (PA) and plasma beta-thromboglobulin (beta TG) values were evaluated in 40 patients affected by chronic airway obstruction (CAO). PA and beta TG were significantly higher than those observed in normal subjects. Beta TG plasma levels were inversely correlated with PaO2, directly with PaCO2 and [H+]. Two h after a venesection of 300-400 ml, no change of beta TG and PA was seen in 10 healthy subjects, while a significant increase of beta TG and PA values was observed in 29 patients. The investigation suggests that in patients with CAO in vivo platelet activation is present. PMID- 2579842 TI - Origin and fine structure of substance P-containing nerve terminals in the facial nucleus of the rat: an immunohistochemical study. AB - The distribution, origin and fine structure of substance P-like immunoreactive (SPI) nerve terminals in the facial nucleus of the rat were investigated by means of immunocytochemistry. SPI-terminals were concentrated in the intermediate and dorsal subnuclei of the facial nucleus. Hemi-transection of the brainstem just rostral to the facial nucleus or at the most caudal level of the medulla oblongata did not cause any change of SPI-terminals in the facial nucleus. Electrical destruction of the various parts of the medulla oblongata clearly demonstrated that SPI-terminals in the intermediate subnucleus were supplied contralaterally from the SPI-neurons in the dorsomedial part of the medullary reticular formation. Most of the SPI-terminals (85%) in the intermediate subnucleus of the facial nucleus were observed to make asymmetric synaptic contacts with large dendrites (mean diameter; 1.26 micron). It was supposed that the contact sites are located on proximal parts of the dendrite. A few SPI terminals (6%) formed axo-somatic contacts with large perikarya filled with numerous cytoplasmic organelles. PMID- 2579843 TI - Roles of proton removal and membrane fluidity in Na+- and Cl(-)-dependent uptake of gamma-aminobutyric acid by mouse brain particles. AB - Proton removal is required for Na+-dependent uptake of GABA into mouse brain microsomal particles (P3) to take place at 0 degrees C and pH 7.3. No temporal coordination was demonstrated to exist between proton removal and GABA uptake processes, ruling out the possibilities that either a proton gradient or proton outflux from the particles is required. Observations on proton dissociation from the particles indicated that the protons are derived from a particulate compartment that is not in pH equilibrium with the bulk solution. Experiments on the effects of temperature on GABA uptake in the presence of 80 mM NaCl alone or with 10 mM triethanolamine (TREA) at pH 7.3 showed that the effects of TREA and temperature were interactive. The relative enhancing effects of TREA on GABA uptake diminished progressively with increasing temperature. The break points in Arrhenius plots obtained in presence and absence of TREA were the same, indicating that the effect of TREA was not on bulk viscosity of the membrane. Measurements made of fluorescence polarization as a function of temperature and of the absorbance-corrected fluorescence using TMA-DPH, a probe believed to be anchored at the lipid-water interface, showed clearly that the characteristic viscosity changes that take place with temperature in the membrane regions through which the probe is distributed were not correlated with the effects of temperature on GABA uptake. It is tentatively concluded that the protons may be attached to the membranes of the P3 particles by strong coulombic interactions in unstirred electrical double layers, possibly both on the inside and outside of particles. The importance of the existence of differences between pH at the surfaces of membranes, possibly both on the inside and outside of the particles, and that of the bulk solutions that bathe them was reiterated. PMID- 2579844 TI - Isopropanol and chlordecone potentiation of carbon tetrachloride liver injury: retention of potentiating action in hepatocyte suspensions prepared from rats given isopropanol or chlordecone. AB - Administration of isopropanol (2.5 ml/kg, po) or chlordecone (15.2 mg/kg, po) potentiated the release of glutamic oxaloacetic transaminase (GOT) into serum 17- or 7-fold, respectively, in rats exposed subsequently to 30 microliter CCl4/kg, po. Hepatocytes isolated from isopropanol-treated rats, incubated with low concentrations of CCl4 (0.3 or 0.9 mM), did not have significant increase in the amount of GOT released after 30 min compared to control cells exposed to CCl4. However, at 3 hr cells from isopropanol-treated rats released 10- or 3-fold more GOT when exposed to 0.3 or 0.9 mM CCl4, respectively, than control cells exposed to CCl4. By hour 5 of incubation this differential of GOT release was not observed. The same dose and time-dependent pattern of potentiated GOT release upon exposure of CCl4 was seen in hepatocytes obtained from chlordecone-treated rats. These results indicate that the potentiation by isopropanol or chlordecone of CCl4-induced release of GOT from liver is retained through the procedures of cell isolation. PMID- 2579845 TI - Effects of intratracheal administration of bleomycin or saline in pair-fed and control-fed hamsters on daily food intake and on plasma levels of glucose, cortisol, and insulin, and lung levels of calmodulin, calcium, and collagen. AB - In the present study, the effects of intratracheal administration of bleomycin have been examined on daily food intake and on plasma levels of glucose, cortisol, and insulin, and on lung levels of calmodulin, calcium, and collagen in hamsters. Since bleomycin treatment caused nutritional deficiency leading to loss of body weight, we have included pair-fed and control-fed as control groups in order to rule out the nutritional deficiency-related effects on these measurements. Bleomycin-treated animals showed a dramatic decrease in daily food intake and body weight as compared to control-fed animals. Bleomycin-treated animals were hyperglycemic when compared to nutritionally comparable pair-fed animals and had plasma glucose levels similar to those of control-fed animals. Plasma cortisol levels in bleomycin-treated and pair-fed animals showed a time dependent increasing trend, whereas plasma insulin levels in both groups tended to decrease. The lung levels of calmodulin and calcium in bleomycin-treated animals were significantly increased when compared with the pair-fed or control fed group. Bleomycin-treated animals had significantly higher levels of lung collagen than pair-fed or control-fed at 7 and 13 days after treatment. The lung collagen content in pair-fed animals was significantly less than that of control fed at 13 days. It was concluded that a disturbance in carbohydrate metabolism and increased lung levels of calmodulin and calcium might be somehow involved in fibroproliferative changes of the lung in bleomycin-treated animals. PMID- 2579847 TI - A structural and dynamic molecular model for the sodium channel of Electrophorus electricus. AB - Chemical logic and single group rotation (SGR) theory are applied to the primary structure determined by Noda et al. [(1984) Nature 312, 121-127] to construct a molecular model of the sodium channel of Electrophorus electricus. Both structural and dynamic aspects of the channel are accounted for, including gating current, sensitivity to changes in membrane potential, channel opening, a binding site for sodium, selectivity for sodium over potassium, capacity for rapid sodium flow, sensitivity to batrachotoxin (or other toxins) and inactivation. PMID- 2579846 TI - [Local anesthetics and their quaternary derivatives as anti-arrhythmia agents]. PMID- 2579848 TI - Halothane inhibits the neurotoxin stimulated [14C]guanidinium influx through 'silent' sodium channels in rat glioma C6 cells. AB - We have investigated the effect of pharmacological agents on [14C]guanidinium ion influx through sodium channels in C6 rat glioma and N18 mouse neuroblastoma cells. The sodium channels of the N18 cells can be activated by aconitine alone, indicating that they are voltage-dependent channels. In contrast, sodium channels in the C6 cells require the synergistic action of aconitine and scorpion toxin for activation and are therefore characterized as so-called silent channels. The general anesthetic halothane used at clinical concentrations, specifically inhibited the ion flux through the silent sodium channel of C6 rat glioma cells. The voltage-dependent channels of the N18 cells were insensitive to halothane at the concentrations tested. PMID- 2579849 TI - Ca2+-dependent inhibition by trifluoperazine of the Na+-Ca2+ carrier in mitoplasts derived from heart mitochondria. AB - The interaction of trifluoperazine and extramitochondrial Ca2+ with the heart mitochondrial Na+-Ca2+ carrier has been investigated. External Ca2+ inhibits the carrier equally in mitochondria and mitoplasts in which the outer membrane is lysed. Sensitivity to Ca2+ is not removed by washing mitoplasts under varied conditions. Trifluoperazine is a potent inhibitor of the carrier in mitoplasts but not in mitochondria. Trifluoperazine inhibition in mitoplasts depends markedly on the presence of extramitochondrial Ca2+ (2 microM). PMID- 2579850 TI - Human plasma kininogens are identical with alpha-cysteine proteinase inhibitors. Evidence from immunological, enzymological and sequence data. AB - Human high- and low-Mr kininogens were shown to be potent inhibitors of cysteine proteinases such as cathepsin L and papain (Ki = 17-48 pM). A strong immunological cross-reaction between the kininogens and low-Mr alpha-cysteine proteinase inhibitor from human plasma was found. Comparison of partial amino acid sequences from high- and low-Mr kininogen and low-Mr alpha-cysteine proteinase inhibitor demonstrated sequence identity for all segments analyzed. These findings suggest that the kininogens and the alpha-cysteine proteinase inhibitors from human plasma are identical proteins. PMID- 2579851 TI - Effect of papain digestion on redox-linked proton translocation in b-c1 complex from beef heart reconstituted into liposomes. AB - Papain treatment of the cytochrome b-c1 complex from beef heart results in partial proteolysis of core protein II, the iron-sulphur protein and the 15-kDa subunit. Under these conditions a significant inhibition of electron flow and complete suppression of proton translocation in the complex reconstituted into liposomes are observed. Kinetic experiments indicate a correlation between the digestion of core protein II and 15-kDa subunit and the suppression of proton translocation. The results suggest an active involvement of polypeptides of the complex in stabilizing the semiquinone species and/or providing pathways to exchange protons between bound quinone systems and aqueous phases. PMID- 2579852 TI - Antigenic determinant and interspecies cross-reactivity of a monoclonal antibody to poly(ADP-ribose) synthetase. AB - A monoclonal antibody (1F4) was prepared against calf thymus poly(ADP-ribose) synthetase. It was classified as IgG1/kappa and its antigenic determinant was localized on the 46 kDa portion of the enzyme molecule which contains the site for the binding of DNA. When calf thymus DNA-binding proteins were subjected to immunostaining after electrophoresis and transblotting to a nitrocellulose filter, the native enzyme (120 kDa) and its endogenous degradation products (80, 64 and 32 kDa) were detected. When the interspecies cross-reactivity was examined using DNA-binding proteins from 6 different sources, 1F4 reacted with the 120- and 32-kDa protein bands in HeLa cells, mouse testis and chicken liver as in the case of calf thymus. These results indicate that the antigenic structures of poly(ADP-ribose) synthetase and its degradation products are highly conserved in various animal cells. PMID- 2579853 TI - Processing of precursor ribosomal RNA and the presence of a modified ribosome assembly scheme in Escherichia coli relaxed strain. AB - An electrophoretic system capable of separating 25 S, 23 S, 17.5 S and 16 S ribosomal RNA (rRNA) species was used to study the synthesis and fate of rRNA during amino acid starvation and resupplementation of E. coli relaxed strain KL99. This E. coli relAl strain responded to an amino acid starvation by increasing the rate of synthesis of 25 S and 17.5 S precursor rRNA. When the limiting amino acid was resupplemented, a previously observed 40-fold increase in the cellular guanosine 5'-diphosphate, 3'-diphosphate content [Mol. Gen. Genet. (1983) 192, 5-9] appeared to cause a reduction in new rRNA synthesis. Following amino acid resupplementation, the precursor 25 S and 17.5 S rRNA accumulated during the amino acid starvation were conserved and processed to 23 S and 16 S rRNA species, respectively. This suggests that a modified ribosome assembly scheme involving stable precursor rRNA exists in relAl bacteria during periods of amino acid limitation and resupplementation. PMID- 2579854 TI - Study of the peptidasic site of cholinesterase: preliminary results. AB - The peptidasic site of highly purified human plasma cholinesterase was investigated using active-site-directed inhibitors. Peptidase activity was assayed taking substance P as substrate. Inhibition by organophosphates indicated that the peptidasic site contained an active serine. The presence of essential histidine residues associated with serine was revealed by histidine modifications. Carboxyl group reagents showed that the active centre contained carboxyl groups in a non-polar environment. The removal of sialic acids did not alter peptidase activity. The peptidasic site of cholinesterase shared many properties with serine proteases sites and esteratic sites of cholinesterases. In addition, with the peptidasic site, as well as the esteratic site, there was always the possibility of 'aging' when inhibited by DFP or soman. PMID- 2579855 TI - Some characteristics of a porcine retrovirus from a cell line derived from swine malignant lymphomas. AB - The characteristics of the enzyme of porcine retrovirus from a cell line derived from swine malignant lymphomas fit with the template specificity and divalent cation requirement for reverse transcriptase. It is further found that the virus particle contains a high molecular mass 70 S RNA as viral genome. PMID- 2579856 TI - Generation of the electrochemical potential of Na+ by the Na+-motive NADH oxidase in inverted membrane vesicles of Vibrio alginolyticus. AB - Inverted membrane vesicles prepared from Vibrio alginolyticus generated a membrane potential (positive inside) and accumulated Na+ by the oxidation of NADH. Generation of the membrane potential required Na+ and was inhibited by 2 heptyl-4-hydroxyquinoline N-oxide, a specific inhibitor of the Na+-dependent NADH oxidase. Collapse of the membrane potential by valinomycin stimulated the uptake of Na+. In contrast, accumulation of H+ was not detected under all the conditions tested. These results suggest that only Na+ is translocated by the Na+-dependent NADH oxidase of V. alginolyticus. PMID- 2579858 TI - Potential for in vitro growth of common bacteria in solutions of 32% dextran 70 and 1.0% sodium carboxymethylcellulose. PMID- 2579857 TI - Newborn response to cationic amphiphilic drugs. AB - Administration of various cationic amphiphilic drugs in utero results in induction of a phospholipid storage disorder in many tissues, particularly in lungs. In addition to the phospholipidosis in utero, drug exposure results in toxicity to the offspring; newborn rats die within 48 h of birth. Although drug induced pulmonary pathological changes appear to be involved in the observed mortality, this relationship remains unclear. In contrast to mammals, administration of cationic amphiphilic drugs to the chick embryo seems not to induce phospholipid storage in the tissues examined. Treatment of newborn rats directly with these drugs also induces phospholipidosis in several tissues including lung and kidney; however, mortality does not occur. Concurrent administration of phenobarbital and chlorphentermine reduces or prevents amphiphilic drug-induced phospholipid storage in newborn rat lung and kidney. Modification of chlorphentermine actions by phenobarbital may be caused by alterations in amphiphilic drug excretion, metabolism, and catabolic phospholipase activity. Evidence thus indicates that regardless of age, animals appear susceptible to the effects of cationic amphiphilic drugs; however, species and tissues examined, as well as specific drug administration, play an important role in the observed qualitative and quantitative responses. PMID- 2579859 TI - Noncardiogenic pulmonary edema secondary to intrauterine instillation of 32% dextran 70. PMID- 2579860 TI - Mechanism and regulation of natural cytotoxicity. Minireview on cancer research. AB - Natural killer (NK) cells comprise a heterogeneous population of effector cells functionally and phenotypically distinct from B cells and mature antigen sensitive T cells, with the capacity to spontaneously lyse target cells of widely different tissue provenance in a genetically unrestricted fashion. As such they have been widely implicated in immunosurveillance against neoplastic and virus infected cells, as well as in the homeostasis of haematopoietic differentiation and regulation of immune function. In common with cytotoxic T cells, the lytic mechanism may be resolved into several discrete stages. Target cell recognition appears to involve several chemical entities, while susceptibility is also influenced by a multiplicity of factors operative at post-recognition stages of the lytic process. NK activity is subject to both positive and negative regulation. The potentiating effects of interferons and interleukin-2, products of activated T cells, indicate a possible pathway by which adaptive immune responses may augment natural cytotoxicity under local physiological conditions. Negative regulation is mediated by certain prostaglandins and a variety of cell types including macrophages, granulocytes and thymocytes as well as subsets of peripheral blood lymphocytes. PMID- 2579861 TI - Antitumor activity of normal human globulin: effects on murine and human erythroleukemic cells. AB - The effect of the antitumor fraction isolated from the alpha 2-globulin region of normal human serum (NHG-I) upon murine (FELC) and human (K562) erythroleukemic cells in vitro was determined. NHG-I inhibited the growth of both actively growing FELC and K562 cells in a dose-dependent manner. However, it has no effect upon mitomycin C treated FELC which were unable to divide nor upon dimethylsulfoxide-induced FELC in stationary phase. These results indicate that NHG-I has a cytostatic effect upon cell growth and suggests that its action may be dependent upon DNA synthesis. This is in marked contrast to TNF, the alpha 2 globulin factor obtained from murine serum which is also not species-specific but whose action upon these cell lines is cytotoxic. PMID- 2579863 TI - Pure alpha-subunit producing tumor derived from a thyrotropic tumor: impaired regulation of alpha-subunit and its mRNA by thyroid hormone. AB - We have recently described a mouse pituitary tumor line which produces only the alpha-subunit of the glycoprotein hormones. This tumor line may be a useful animal model to study autonomous pituitary tumors which secrete only alpha subunit. Our pure alpha-subunit producing tumor was derived from a thyrotropic tumor which secreted intact TSH as well as free alpha-subunit. Our current studies compare the regulation of alpha-subunit biosynthesis in a conventional thyrotropic tumor and the alpha-subunit producing tumor. Thyroxine or triiodothyronine administration to mice bearing the alpha-subunit producing tumor resulted in no change in plasma alpha-subunit concentration, and a 10-19% reduction in tumor alpha-subunit mRNA concentration that was not statistically significant. In contrast, thyroxine administration to mice bearing the thyrotropic tumor resulted in an 81% reduction in plasma alpha-subunit concentration, and a 75% reduction in tumor alpha-subunit mRNA concentration (P less than 0.01). Other studies using a cDNA specific for thyrotropin-beta (TSH beta) failed to detect TSH beta mRNA in the alpha-subunit producing tumor, while TSH beta mRNA was easily detected in the conventional thyrotropic tumor. We conclude that during the development of the alpha-subunit producing tumor from a thyrotropic tumor, loss of TSH beta mRNA was also associated with an impaired capacity for thyroid hormone to decrease concentrations of alpha-subunit mRNA. PMID- 2579862 TI - Influence of cyclic nucleotides on receptor binding, immunological activity, and microheterogeneity of human choriogonadotropin synthesized in placental tissue culture. AB - The regulation of the biosynthesis of choriogonadotropin (hCG) in tissue culture by human first trimester placenta in the presence of the following cyclic nucleotides and 3-isobutyl-1-methylxanthine (IBMX) was studied (concentrations in parentheses): IBMX (0.1 mM), cAMP (1 mM) + IBMX (0.1 mM), cGMP (0.1 mM) + IBMX (0.1 mM), 8-bromo-cAMP (0.5 mM) and 8-bromo-cGMP (0.5 mM). The medium concentration of hCG follows an optimum curve at all conditions, showing highest values at day 3 of the culture. The efficacy of the substances to cause an increase in the hCG medium concentration was in the following order: IBMX less than control less than 8-bromo-cGMP = 8-bromo-cAMP less than cGMP + IBMX less than cAMP + IBMX. The synthesized hCG was examined with respect to its receptor binding activity (LH/hCG receptor of rat testes), the activities to stimulate adenylate cyclase as well as testosterone biosynthesis in purified mouse Leydig cells, the immunological activity, and the microheterogeneity in isoelectric focusing. Only in the presence of 8-bromo-cAMP, 8-bromo-cGMP, and cGMP + IBMX was hCG synthesized, which differs significantly in the investigated properties from hCG of the control cultures. Only in the presence of 8-bromo-cGMP is the ratio of receptor binding activity/immunological activity optimal (near 1). In the presence of both 8-bromo-cAMP and 8-bromo-cGMP, microheterogeneity of hCG in isoelectric focusing was diminished and the synthesis of more acidic hCG subpopulations was favoured. PMID- 2579864 TI - Children with minor neurodevelopmental disorders. III: Neurological and neurodevelopmental problems at age 10. AB - Two previous papers have presented the results of behavioural and educational follow-up at age 10 of children diagnosed at age seven having minimal brain dysfunction (MBD), motor perception dysfunction (MPD) or attention deficit disorder (ADD), and normal control children. The present paper is concerned with the neurological and neurodevelopmental problems of these groups of children at age 10. 25 per cent of the children with severe MBD and almost 55 per cent with mild to moderate MBD had had neurological problems at age seven, but no longer had any demonstrable neurological deficit at age 10. The findings were similar in the MPD group, and the neurological status of the ADD group was similar to that of the controls. These findings are in contrast to the high rates of severe behavioural and/or school-achievement problems among the children in the MBD group, and indicate that the three-year prognosis with regard to neurological dysfunction is fairly good, but is gloomy as far as behavioural and school achievement problems are concerned. PMID- 2579865 TI - Effect of antigastrin (SC-15396) on amylase release and 2-deoxyglucose uptake in mouse pancreatic acini. AB - The effects of antigastrin (SC-15396) on amylase release and 2-deoxyglucose uptake were studied in dispersed acini from mouse pancreas. Antigastrin at concentrations between 0.5 and 2 mM inhibited cholecystokinin (CCK)-stimulated amylase release and 2-deoxyglucose uptake in a dose-dependent fashion. Antigastrin at concentrations between 0.5 and 2 mM inhibited carbachol-stimulated amylase release and 2-deoxyglucose uptake as well. In addition, the drug (2 mM) inhibited bombesin-stimulated amylase release and 2-deoxyglucose uptake. In contrast, the stimulation of amylase release by Ca2+ ionophore A23187 was not inhibited by antigastrin. The results, therefore, suggest that antigastrin nonselectively inhibits the actions of these secretagogues probably at their receptor sites. PMID- 2579866 TI - Effects of acute hypercalcemia on exocrine pancreatic secretion in the cat. AB - To investigate the effects of acute hypercalcemia on exocrine pancreatic secretion, anesthetized cats were given calcium intravenously. Increasing hypercalcemia (3.7-6.3 mmol/L) evoked a dose-dependent increase in enzyme output that was 12 times greater than in normocalcemic controls (p less than 0.001) and was 60% of subsequent maximal stimulation with intravenous cholecystokinin (CCK). The effect of hypercalcemia on enzyme secretion was abolished when CCK was administered 60 min before calcium and at a dose to cause maximal enzyme output. Atropine did not prevent the calcium-induced increase in enzyme secretion. Pancreatic fluid and bicarbonate outputs were not influenced by hypercalcemia during intravenous administration of small amounts of secretin, but were increased by addition of CCK to the secretin infusion. Hypercalcemia did not induce macroscopic or light-microscopic changes in pancreatic morphology. Plasma levels of both CCK and gastrin were increased (p less than 0.01) during hypercalcemia, with and without precalcium administration of CCK; atropine significantly inhibited (p less than 0.05), but did not abolish the calcium induced releases of both peptides. These data suggest that in the anesthetized cat, acute hypercalcemia induced by intravenous calcium infusion stimulates pancreatic secretion of enzymes, but not fluid and bicarbonate. Acute hypercalcemia also causes release of CCK and, as shown previously, gastrin. The findings suggest that the stimulatory effect of hypercalcemia on pancreatic enzyme secretion is not dependent on intact cholinergic pathways and is probably not exclusively mediated by release of CCK or gastrin. PMID- 2579867 TI - Protection by dietary proteins against the effects of bile acids on rat jejunum and stomach. AB - Because bile acids bind to certain proteins we examined whether the effect of dihydroxy bile acids on jejunal water transport and gastric mucosal function could be blocked by the presence of protein. In the rat jejunum 2.5% bovine serum albumin blocked the secretion of water and electrolytes induced by 2 mM deoxycholate, whereas 5% ovalbumin, which does not bind bile acids, had no effect. Bovine serum albumin protected large unilamellar liposomes from damage by taurodeoxycholate and reduced the monomer concentration of taurodeoxycholate, whereas ovalbumin afforded no protection. In equilibrium dialysis studies whey protein and bovine serum albumin reduced the free taurodeoxycholate concentration (150 mM HCl enhanced this effect). In the rat stomach taurodeoxycholate (2.5 or 10 mM) in the presence of 150 mM HCl reduced potential difference and enhanced sodium secretion and hydrogen ion loss. These effects were reduced in the presence of whey protein. We conclude that proteins that bind bile acids have the potential to protect mucosal membranes from the adverse effects of bile acids. PMID- 2579869 TI - Fibrin sponge plugging of hemorrhage from laparoscopic biopsy. PMID- 2579868 TI - Jejunal secretory effect of intraduodenal food in humans. A comparison of mixed nutrients, proteins, lipids, and carbohydrates. AB - The effect of the presence of food in the intestinal lumen on fluid transport by an intestinal loop isolated from nutrients is debatable and seems to be species dependent. The aim of the present study was to investigate this effect in humans. Fluid and ion transport by a 30-cm-long jejunal loop was measured by the perfusion of a plasmalike electrolyte solution below an occlusive balloon inflated at the angle of Treitz. At the same time, the duodenum was infused at the papilla by saline (control period) or one of the following solutions (test period): protein hydrolysate, starch hydrolysate, lipids, or mixed nutrients. The four solutions (pH 7; 300 mosmol/L; 540 kcal/L) were infused in 6 normal subjects in a randomized order. In 6 further subjects, two other loads of intraduodenal lipids (120 and 1080 kcal/L) were tested according to a similar protocol. Blood samples were taken serially for radioimmunoassays of gastrin, secretin, cholecystokinin, pancreatic polypeptide, gastric inhibitory polypeptide, vasoactive intestinal polypeptide, motilin, and somatostatin. Intraduodenal mixed nutrients, proteins, and lipids significantly reduced water and ion jejunal net absorption or induced a net secretion (without dose-effect relationship for lipids) and stimulated plasma cholecystokinin, pancreatic polypeptide, and gastric inhibitory polypeptide. Intraduodenal lipids also stimulated circulating levels of gastrin and vasoactive intestinal polypeptide. Intraduodenal sugars did not change jejunal fluid and ion transport and significantly increased plasma gastric inhibitory polypeptide. Covariance analysis showed transjejunal fluid movements to be linked with plasma levels of cholecystokinin. We conclude that an intraduodenal mixed meal exerts a secretory effect on a jejunal loop isolated from the nutrients and that this effect is due to the lipid and protein content of the meal; our data are compatible with a mediation of this phenomenon by cholecystokinin. PMID- 2579870 TI - [Extremely high alpha-fetoprotein levels in a puncture specimen with few cells following amniocentesis and interpretation by sonography]. AB - We report on a prenatal diagnosis with high alpha-fetoprotein level and a positive acetylcholinesterase activity in a presumptive amniotic fluid. Ultrasonographic examinations revealed a hydropic fetus with a nuchal cystic hygroma. Chromosome analysis of the aborted foetus ascertained the suspected Turner syndrome. The highly elevated alpha-fetoprotein concentration and the positive acetylcholinesterase activity as well as the absence of the cells in the fluid make it clear, that the punctate originated from a cystic hygroma. Other cases from the literature are discussed. PMID- 2579871 TI - [Child development after abdominal version of the fetus from breech presentation to vertex presentation near term]. AB - The prospective study presented here describes the results of follow-up examinations of the developmental stage of 116 children born between 1977 and 1980 in whom abdominal version of the foetus from breech presentation to vertex presentation was performed near term. The children were examined according to the Denver Developmental Screening Test at the age of 2 to 5 3/4 years in various fields (social contacts, minor motor functions and adaptation, speech and major motor functions). Children with abnormal findings were subjected to special examinations. Those with disturbed development were re-examined after one year. In the entire group of children there were four with psychomotor retardation of speech, and two further children with minimal cerebral motor disturbances. The children had been detected early during infancy. These results, classified as secondary morbidity (disturbances of speech and minimal cerebral motor disturbances) were analysed taking into account the results of version (successful and unsuccessful version) and other obstetric factors (course of pregnancy and birth, method of delivery, biochemical examinations during and after birth, age of mother and socioeconomic status of parents). PMID- 2579873 TI - PY 108-068: a calcium antagonist with an unusual pattern of cardiovascular activity. AB - PY 108-068 (PY) is a potent dihydropyridine derived calcium antagonist, which is light-stable enough to allow experiments in vitro to be done under normal daylight. It potently antagonized depolarization-induced contraction of rabbit aorta (EC50: 4 X 10(-9) M) but not receptor-stimulated contraction (EC50 much greater than 10(-5) M). It also decreased the rate of spontaneously beating guinea-pig and rabbit atria very potently (EC25 2.9 and 4.3 X 10(-9) M respectively) but considerably higher concentrations were needed for negative inotropic effects on guinea-pig left atria or rabbit papillary muscles (EC25 1.5 and 1 X 10(-7) M respectively). In open chest dogs PY (10 micrograms/kg i.v.) increased coronary flow and cardiac output, lowered blood pressure, and tended to decrease heart rate while myocardial contractile force was unchanged. Myocardial oxygen consumption, however, was decreased despite the absence of cardiodepression. Similar results with respect to the systemic circulation were observed in cats. The effects of PY on the vascular beds of a large number of organs were investigated using tracer microspheres. PY effected regional vasodilatation in the heart, brain and skeletal muscle. Antivasoconstrictor effects of PY were investigated in similar cat experiments by pretreating the animals with angiotension II infusions. The vasoconstrictor effects of angiotensin II on the vessels of the kidney, stomach and small intestine were antagonized, even though no vasodilatation had been seen in these regions in the previous experiments without the vasoconstrictor pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579872 TI - [Prenatal diagnosis of neural tube and abdominal wall defects in the 2d trimester]. AB - Combined alpha-fetoprotein screening in serum and specified sonographic examination has proved useful in prenatal diagnosis of neural tube and abdominal wall malformations. 207 amniocenteses were performed within a period of 3 years due to pathologic serum alpha-fetoprotein values and/or abnormal sonographic findings. 101 amniotic fluid specimens showed an increase of alpha-fetoprotein of more than 2.5 times the average value. 60 malformed neural tubes, 17 foetuses with abdominal wall defects, as well as 2 other malformations, were diagnosed. "Open" defects, as well as 17 false positive AFP values, were discovered through the electrophoretic presence of ZNS-specific acetylcholinesterase in the amniotic fluid. PMID- 2579874 TI - Changes in mouse brain serotonin turnover following chronic imipramine administration. AB - Mice were injected daily for 2 weeks with saline, tryptophan or p chlorophenylalanine, alone or in combination with the tricyclic antidepressant imipramine. Serotonin turnover in several brain regions was determined by the accumulation of serotonin after pargyline and 5-hydroxyindoleacetic acid after probenecid. Both methods agreed closely. Imipramine tended to depress serotonin turnover. This effect was more marked in hypothalamus, which has high serotonin activity, and was much less in cerebellum, which has low serotonin activity. Chronic imipramine treatment completely abolished the increase in serotonin turnover induced by tryptophan, but had no effect on serotonin turnover in mice treated with p-chlorophenylalanine, which itself reduced serotonin activity. PMID- 2579875 TI - Immunoreactivity for Met-enkephalin and substance P in cells of the adenohypophysis of larval and adult sea lampreys, Petromyzon marinus. AB - Procedures for localizing immunoreactive Met-enkephalin and substance P were applied to the adenohypophysis of larval and adult sea lamprey, Petromyzon marinus. Immunopositive reaction to anti-Met-enkephalin antiserum was found in certain adenohypophysial cells of both larvae and adults. This reaction was specific, as judged by preabsorption of the antiserum with synthetic Met enkephalin and subsequent elimination of the immunoreaction. An immunopositive response to one of three anti-substance P antisera, also selective for certain adenohypophysial cells was obtained in both larval and adult glands. This reaction was not completely eliminated by preabsorption with authentic substance P. Although the substance P immunoreaction is not specific for authentic mammalian substance P, its localization is characteristic and distribution of cells exhibiting it is described. Immune-staining of Met-enkephalin was seen in most of the cells of the rostral pars distalis, and it was as strong or stronger in larvae (ammocoetes) of Petromyzon as it was in adults. The substance P response was found in about half of the cells of the caudal pars distalis and in a few cells of the rostral pars distalis. In ammocoetes substance P staining was limited to a few cells of the caudal pars distalis, and no cells in the rostral pars distalis were stained. Thus, Met-enkephalin staining in Petromyzon is a general property of cells in the rostral pars distalis both in larvae and adults and cannot be correlated with such events in the life cycle as metamorphosis or reproduction. On the other hand, cells containing materials reactive with the anti-substance P serum appear at a very low level in the larva and grow in number and intensity of staining in a time pattern that parallels development of reproductive capacity. Furthermore, the disparity in time of synthesis and adenohypophysial and cellular distribution of Met-enkephalin-like and substance P like materials indicates that these two peptides are not functionally related, as has been suggested for some higher vertebrates. PMID- 2579876 TI - Pleural effusions: meeting the diagnostic challenge. AB - Etiologies of complicated pleural effusions include infections, malignancies, and rheumatologic disorders. Appropriate diagnostic studies are determined by specific clinical situations. Possible causes of benign pleural effusions should be considered first. Commonly overlooked diagnoses include chronic effusions initially due to transudative processes, benign asbestos effusions, and traumatic effusions. PMID- 2579877 TI - Effects of S-596 and carteolol, new beta-adrenergic blockers, and flurbiprofen on the human eye: a fluorophotometric study. AB - The effects of S-596 and coarteolol, new beta-adrenergic blockers, were studied by means of the oral fluorescein method. Transfer coefficients by diffusion, kd.pa, and by flow, kfa, were estimated in a total of 11 normal young volunteers, in whom the drug was instilled in one eye and the placebo in the fellow eye. With 0.5% dl-S-596, kd.pa increased to 124 +/- 9% (mean +/- SD) and kfa decreased to 67 +/- 10% of the control eye. With 1% dl-carteolol, kd.pa increased to 121 +/- 4%, and kfa decreased to 84 +/- 11% of the control eye. Both S-596 and carteolol increased iris permeability and decreased the aqueous flow rate significantly. In a group of 13 cases, intracapsular extraction of senile cataract was carried out with postoperative routine instillations, and in another group of 7 cases, it was carried out with additional topical flurbiprofen, a new nonsteroidal anti inflammatory drug. Flurbiprofen ophthalmic solution (0.1%) was instilled 3, 2, 1, and 0.5 h before the surgery and 4 times a day postoperatively. On the 6th postoperative day, a fluorophotometric study was carried out using oral fluorescein, and a coefficient that reflects the permeability of the blood aqueous barrier after the cataract surgery was calculated. It was found that additional topical flurbiprofen considerably suppresses the disruption of the blood-aqueous barrier. PMID- 2579878 TI - Lysophosphatidylcholine increases rat ileal permeability to macromolecules. AB - The influence of lysophosphatidylcholine (LPC) on macromolecular permeability in the distal ileum has been studied. Using a rat experimental model, we determined the intestinal permeability to different sized dextrans (3000-70 000 daltons) and bovine serum albumin (BSA) in the absence and presence of LPC. We also examined the morphology of the ileal mucosa after deposition of LPC in the gut lumen, and determined N-acetyl-beta-glucosaminidase, 5'-nucleotidase, and alkaline phosphatase activities in suspensions of isolated mucosal cells and different concentrations of LPC. We found that 20 mM LPC damaged the ileal mucosa and that it increased its permeability to all the molecules investigated. Moreover, mixtures of mucosal cells and 0.01-1 mM LPC showed increased N-acetyl-beta glucosaminidase activity: the higher the LPC concentration, the higher the enzyme activity. These findings indicate that LPC, a naturally occurring surfactant in the intestine, might damage mucosal cells and release lysosomal enzyme activity, and that higher LPC concentrations may impair the mucosal barrier function and increase the gut permeability to macromolecules such as proteins. This could have relevance to the development of various disease states, in which increased intestinal absorption of macromolecules is of importance. PMID- 2579879 TI - [Therapy of ventricular arrhythmias with propafenone]. AB - In 16 patients with angiographically-documented coronary artery disease and repetitive ventricular responses the effects of oral propafenon 300 mg t.i.d. on the continuous 24-hour ECG were analyzed in a study carried out according to a double-blind, randomized, crossover, placebo-controlled protocol. Comparisons were made for the number of couplets (Lown IVa) and ventricular tachycardias (Lown IVb) as well as the overall incidence of ventricular premature beats during the two last days of a five-day placebo phase and on the second and third day of treatment with propafenon. In 15 further patients with electrocardiographically documented sustained ventricular tachycardias, the effect of intravenous propafenon (1.5 mg/kg in three minutes) was also investigated. Repeat electrophysiologic studies were performed in eight of the 15 patients after two to 13 days of continuous treatment with oral propafenon 300 mg t.i.d. The stimulation protocol incorporated delivery of a maximum of four extra stimuli during sinus rhythm and during apical right ventricular stimulation at each of four basic intervals (600, 500, 400 and 330 ms) as well as burst stimulation with intervals between 300 and 250 ms. Stimulation was terminated after induction of sustained ventricular tachycardia. In patients in whom ventricular tachycardia could be induced prior to medication with one or two stimuli, after propafenon no more than two extra stimuli were applied. As compared with placebo, propafenon led to a more than 90% reduction in couplets in 56% of the patients and in 64% of the patients there was a complete suppression of ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579880 TI - Lack of in vivo activation of the interferon system in HBsAg-positive chronic active hepatitis. AB - The in vivo activation state of the interferon system was biochemically evaluated in patients with HBsAg-positive liver disease by assaying the interferon-induced enzyme, 2'5'-oligoadenylate synthetase, in peripheral blood mononuclear cells. All patients with chronic active hepatitis had normal levels of enzyme activity. Increased values were found in 77% of patients with acute hepatitis, 50% of those with chronic persistent hepatitis and 54% chronic healthy carriers. These results provide evidence for lack of activation of the interferon system in HBsAg positive chronic active hepatitis and support the hypothesis that an in vivo defective interferon response may aid in development of chronic active hepatitis. PMID- 2579882 TI - Interferon and hepatitis B. PMID- 2579881 TI - Rheumatoid factor-like reactants in sera proven to transmit non-A, non-B hepatitis: a potential source of false-positive reactions in non-A, non-B assays. AB - Convalescent phase non-A, non-B (NANB) human and chimpanzee sera were utilized in a solid-phase radioimmunoassay (RIA) in an attempt to identify a specific NANB antigen in human plasma, plasma-derived pellets and NP-40 disrupted pellets proven to transmit NANB infection to chimpanzees. RIA reactivity was noted in 5 of 8 pedigreed NANB infectious plasmas, but did not appear to be virus-specific. The RIA reactive fraction: (i) had a density of 1.27 to 1.32 gm per cm3 in cesium chloride; (ii) showed immunoreactivity corresponding to normal IgM, but peak RIA activity coincided with an aberrant IgM having a peak sedimentation coefficient of 56 S, and (iii) eluted at higher pH (5.6 to 5.0) than normal IgM on chromatofocusing columns. The reactant shared properties with rheumatoid factor in that it was absorbed by aggregated IgG and was unstable to 2-mercaptoethanol, but it did not react in standard agglutination tests for rheumatoid factor. The reactant was detected in both the acute and chronic phase of NANB infections in chimpanzee and man. By reacting with IgG in presumptive NANB convalescent sera, this aberrant rheumatoid factor could simulate a NANB antigen and represent a cause of false-positive reactions in putative NANB assays. PMID- 2579883 TI - Lymph-vessel embolism in a case of Whipple's disease. AB - A case of Whipple's disease is described where the lymphatics in the regional lymph nodes appear to be obstructed by embolized macrophages, containing the characteristic PAS positive bacillary material. It is suggested that the regional lymphangiectasia in Whipple's disease may in part result from such cellular embolism. PMID- 2579884 TI - Laryngeal neuroendocrine tumour with features of a paraganglioma, intracytoplasmic lumina and acinar formation. AB - A supraglottic laryngeal neuroendocrine tumour in a 71-year-old female is presented. In addition to the typical features of extra-adrenal paragangliomas it showed unusual, numerous intracytoplasmic lumina and occasional true acini with accumulation of alcian blue and PAS positive secretory product in them which led originally to an erroneous diagnosis of metastatic adenocarcinoma. Ultrastructurally, the tumour was composed of light and dark chief cells containing varying numbers of dense-core secretory granules. Intracytoplasmic lumina and true acini contained microvilli with glycocalyceal material and varying amounts of membranous and amorphous material, possibly secreted via small, smooth-surfaced cytoplasmic vesicles but typical mucin granules were not seen. These features have not been previously described in laryngeal paragangliomas but are seen in endocrine tumours of other sites and have been used as an argument in favour of an endodermal rather than ectodermal origin for endocrine cells in those sites. Laryngeal paragangliomas are often malignant and the presence of spasmodic pain appears to be the most reliable indication of possible malignancy, histological criteria being as yet poorly defined. PMID- 2579885 TI - A morphological and immunocytochemical study of a distinctive variant of ductal carcinoma in-situ of the breast. AB - Because so-called 'carcinoid' tumour of the breast has proven to be a difficult entity to define, we studied in-situ carcinoma as there were reasons to believe that this might help clarify the complex problems involved. We studied a consecutive series of 30 cases of ductal carcinoma in-situ (DCIS) by light microscopy and silver impregnation methods and identified a relatively common endocrine variant of DCIS. This variant was studied by immunocytochemical and ultrastructural methods, using conventional DCIS as a control. Endocrine DCIS is identified by its organoid pattern, stromal 'inclusions', festooned structure and a distinctive type of polypoid invagination. It is argyrophilic and rich in neuron-specific enolase. Ultrastructurally it contains abundant dense core granules which are impregnated selectively by Grimelius' method. This tumour type frequently contains peptide hormones of the ACTH family. Three of seven cases contained cells reactive for ACTH and corticotropin-like intermediate lobe peptide CLIP or their precursor, pro-opiomelanocortin. A fourth tumour contained neurotensin, recently identified in a variety of endocrine tumours. Argyrophil invasive carcinomas are a much more heterogeneous group of tumours than argyrophil DCIS and only a minority have an endocrine structure comparable to that described here. PMID- 2579886 TI - Giant nodular ovaries with aberrant follicles. AB - Two cases of an unusual variant of the Stein-Leventhal syndrome and ovary are described and two similar reported cases reviewed. Clinically three of the patients had a delayed menarche followed by irregular periods and one had irregular menorrhagia. Pathologically all four had large firm nodular ovaries of 6-9 cm in diameter, showing a gross excess of stroma and distorted or fragmented atretic follicles with unusual granulosal cell persistence. Both grossly and microscopically, ovaries of this type are liable to be mistaken for tumours, but there is no good evidence that they are either neoplastic or pre-neoplastic. PMID- 2579888 TI - B- and T-cell subsets in follicular centroblastic/centrocytic (cleaved follicular center cell) lymphoma: an immunohistologic analysis of 26 lymph nodes and three spleens. AB - Follicular centroblastic/centrocytic (CB/cc/F), or cleaved follicular center cell, lymphomas are known to contain admixtures of B cells and, often, numerous T cells. To analyze the presence and distribution of B and T cells and their subsets in CB/cc/F lymphomas, 26 lymph nodes and three spleens (from 24 patients) were studied with a panel of monoclonal antibodies and peanut lectin by the avidin-biotin immunoperoxidase technique on frozen sections. Immunoglobulin studies revealed monoclonal neoplastic follicles in most cases, although cells of the nondominant light chain were occasionally present. Rarely, the follicles showed both kappa and lambda light chains or were immunoglobulin-negative. Although monoclonal mantles were observed in only one case, more than half of the nodes demonstrated monoclonal interfollicular infiltrates. In most cases the phenotype of the follicular cells was similar to that of the predominant cells in the normal follicles. Interfollicular lymphomatous cells had variable phenotypes that, unlike the normal situation, sometimes resembled those in the follicles. Phenotypic variation was present within single neoplastic clones and sometimes suggested more mantle-like differentiation. Phenotypic changes were also observed in repeat biopsies. T cells, usually predominantly of the T-helper phenotype, were present in variable numbers in all cases. Although present in the neoplastic follicles, they were usually more common in the interfollicular areas. Six nodes and two spleens had definite rims composed predominantly of T cells around neoplastic follicles. Apparently "activated" (Tac-positive) T cells were often present and showed accentuation around the follicles in some cases. Thus, CB/cc/F lymphoma is a malignant lymphoma that closely resembles follicular hyperplasia but that also has distinctive features. PMID- 2579887 TI - Limitations encountered in the application of tissue section immunodiagnosis to the study of lymphomas and related disorders. PMID- 2579889 TI - Epididymal melanotic neuroectodermal tumor of infancy. AB - Six melanotic neuroectodermal tumors of infancy arising in the epididymis were reported previously. Each followed a benign clinical course. In the seventh case of such a tumor, reported herein, an elevated serum alpha-fetoprotein level returned to normal following excision of the tumor. Urinary and serum tumor markers may be useful for following the course of these tumors in the future. PMID- 2579890 TI - Cytologic demonstration of differential activity of rRNA gene clusters in different human tissues. AB - rRNA gene activity was evaluated by cytologic methods in cultured human cells from two different tissues grown under controlled experimental conditions. The modal and average numbers of silver positive nucleolus organizers (NOs) per cell as well as the distribution of cells with different numbers of silver positive NOs and different combinations of D- plus G-group silver stained chromosomes, were evaluated. Statistically significant differences in the average number of silver positive NOs per cell between leukocytes and fibroblasts grown under standard experimental conditions have been demonstrated. The observed differences became sharper in cells cultured under more restrictive conditions. Also, differences in the frequency of silver positivity of specific chromosomal NOs located on individually identified chromosomes were observed in cells from the same tissue. Furthermore, differences in the frequency of activation of rDNA clusters located on the same chromosome were also observed between cells from the two tissues. The possible biologic meanings of these findings are discussed. PMID- 2579891 TI - New classes of common fragile sites induced by 5-azacytidine and bromodeoxyuridine. AB - Two new classes of common fragile site seen in chromosomes from blood lymphocyte cultures are reported. The first class is induced in bands 1q42 and 19q13 by 5 azacytidine (5-AZA). Maximum induction of these fragile sites occurs when the 5 AZA is added 5-8h prior to harvest. The second class is induced in bands 6q13, 9p21, and 10q21 by bromodeoxyuridine (BrdU). In this instance maximum induction occurred if the BrdU was added 4-6h prior to harvest. The known fragile sites, both rare and common, are summarised. PMID- 2579892 TI - Chromosomal R-banding with a monoclonal antidouble-stranded DNA antibody. AB - A monoclonal anti-DNA antibody (HB2) specific for poly dG- poly dC nucleotides was used to stain metaphasic lymphocyte or amniotic cell human chromosomes. HB2 fixation was revealed using either a peroxidase- or a rhodamine-labeled anti mouse immunoglobulin antiserum. The staining pattern of the chromosomes was dependent on the HB2 concentration: R-banding could be observed at high antibody dilution. Previous trypsinization of metaphasic preparations demonstrated a precise and reproducible typical R-banding independent of the HB2 concentration. This technique appears to be an interesting alternative to other R-banding procedures. The specificity of the antibody allows a better understanding of the biochemical mechanism of R-banding. PMID- 2579893 TI - [Determination of alpha-2-macroglobulin concentration using immunologic and amidolytic methods in diabetics and kidney patients]. AB - An increased alpha-2-macroglobulin level and a decreased functional capacity of the mononuclear phagocytic system in diabetics appears to be another important factor in the pathogenic cause of micro- and macro-angiopathy. Additionally, the disturbed immunobalance, especially in the micro-environment as well as the type and intensity of infections and inflammatory reactions are involved. PMID- 2579894 TI - Control of immune interferon release by cytotoxic T-cell clones specific for influenza. AB - We have studied the release of immune interferon (IFN-gamma) by influenza specific cytotoxic T-cell (Tc) clones. IFN-gamma release is entirely dependent on specific antigen recognition or mitogen treatment and correlates inversely with the growth rate of the clone, while no differences in cytotoxic activity can be discerned at the different stages of Tc maturation. Although the mitogen Con A provides a more powerful stimulus for IFN release by Tc clones, specific antigen leads to a more rapid secretion, starting within 2 hr of contact with Tc clones and their specific targets. This may be of significance in an infection, providing a quick, but localized, mechanism to prevent viral spread. We also examined whether ligand interactions with T-cell surface glycoproteins Lyt-2 or LFA-1, important in Tc recognition, affected IFN release. Monoclonal antibodies to both Lyt-2 and LFA-1 block specific target cell lysis of Tc clone BA4, but do not affect Tc clone T9/5. This latter finding adds LFA-1 to the list of T-cell surface components which are not always essential for target cell recognition. Antibody to Lyt-2 blocked antigen-induced IFN-gamma release by all Tc clones studied, whilst two monoclonal antibodies to LFA-1 had little or no effect. Thus, the Lyt-2 molecule plays a role in the regulation of IFN secretion. PMID- 2579895 TI - Production of a T-cell hybrid producing a lymphokine stimulating eosinophil differentiation. AB - Spleen cells from mice undergoing a parasite-induced eosinophilia were fused with an azaguanine-resistant subline of the thymoma BW5147. A stable T hybrid (NIMP TH1) was isolated and selected by recloning repeatedly by limiting dilution. The hybrid nature of NIMP-TH1 was confirmed by its expression of both parental alleles of Thy-1 and by chromosome analysis (modal chromosome number 102). On stimulation with phorbol myristate acetate, this hybrid releases a soluble activity which acts as a stimulator of eosinophil differentiation in vitro. Addition of hybrid conditioned medium to bone marrow cultures results in a selective stimulation of eosinophil production with no detectable increase in neutrophil or macrophage differentiation. The lymphokines interleukin-2 (IL-2) and interferon (IFN) are undetectable in NIMP-TH1 conditioned media. Although at high concentrations NIMP-TH1 supernatants are able to support very low levels of DNA synthesis in an IL-3-dependent cell line, and IL-3 appears to support low levels of eosinophil differentiation, dose-response curves show that the factor produced by NIMP-TH1 can be clearly segregated from IL-3 by its marked specificity for cells belonging to the eosinophil lineage. The factor present in these supernatants has been provisionally termed eosinophil differentiation factor (EDF). PMID- 2579896 TI - The T-cell mediated immune response to Schistosoma mansoni. I. Generation of stage-specific, MHC-restricted proliferative T-cell clones to soluble egg antigens. AB - A panel of T-cell clones reactive to the soluble egg antigen (SEA) of Schistosoma mansoni is described. The proliferative responses of the primary immune lymph node (LN) cells and T-cell clones to different schistosome antigen preparations (cercarial extract (CE), live or dead schistosomula, adult worm extract, and soluble egg antigen) were compared. Primary immune LN cells could not distinguish between these schistosome antigen preparations. However, when a total of 22 T cell clones was analysed, a complex pattern of both stage-specific and common (or cross-reactive) antigen reactivity was observed. These patterns have been grouped into four types: (i) five clones were reactive to all different schistosome antigen preparations; (ii) two clones were reactive only to SEA, CE and schistosomula; (iii) three clones were reactive only to SEA and cercariae; (iv) twelve clones were reactive to SEA antigen alone. The T-cell clones were identified as Thy-1-positive cells. All the clones were able to respond to exogenous IL-2 after antigenic stimulation. However, there was a variable degree of IL-2 responsiveness when compared with antigen-specific stimulation. Four T clones were selected for further studies on the genetic control of the proliferative response to schistosome antigens. One of the proliferative T clones was restricted by the IA subregion of the major histocompatibility complex (MHC), and the other three clones are restricted by the IE (AeE alpha) subregion. PMID- 2579897 TI - Separation and characterization of a subset of human T8+ cells which function as antigen-presenting and contrasuppressor cells. AB - The lectin Vicia villosa (VV) binds preferentially a subset of T cells. Separated VV-adherent cells (AC) do not generate helper function alone, but when added to VV-non-adherent cells (NAC), they can present streptococcal antigen (SA) and induce helper function as effectively as monocytes, at a ratio of 1 VV-AC to 4 VV NAC. Further separation into a T8+ subset of VV-AC and reconstitution with T4+ helper cells (HC) has established that the T8+ VV-AC induces T4+ cells to helper activity. However, in addition to antigen presentation, the T8+ subset of VV-AC has a contrasuppressor function, for it can prevent T8+ suppressor cells from inhibiting T4+ HC function. The results suggest that a T8+ subset can present antigen to T4+ HC, activate helper function and prevent suppression. The T8+ VV AC may have considerable biological significance in its dual function of countering the dominant suppressor activity and presenting antigen to induce helper activity. PMID- 2579898 TI - Appearance of delayed-type hypersensitivity effector cells in murine gut mucosa. AB - Feeding of a protein antigen, human gamma globulin (HGG), to BALB/c mice prior to parenteral immunization resulted in the abrogation of a delayed-type hypersensitivity (DTH) response to challenge with that antigen. Unlike parenterally immunized mice, HGG-fed mice were unable to transfer DTH to naive syngeneic recipients using peripheral lymph node lymphocytes. Co-transfer experiments ruled out the possibility of a suppressor cell in the orally immunized mice operating on DTH effector cells. Intra-epithelial lymphocytes (IELs) from mice immunized either orally or parenterally were able to transfer a DTH reaction to unimmunized recipients, while mesenteric lymph node lymphocytes from orally, but not parenterally, immunized donors were capable of transferring DTH. The implications of these results for investigations of gastrointestinal disorders with a suspected immunological aetiology are discussed. PMID- 2579899 TI - Antigenic relationship between the alpha-chain of C3, a leucocyte-surface antigen involved in the activation of phagocytic cells, and a 50,000 MW B-cell antigen. AB - A monoclonal antibody, M522, reacting with human monocytes, neutrophils and a proportion of non-adherent PBL in a pattern similar to OKM-1 and anti-Mo-1, and precipitating a dimer of MW 165,000 and 100,000 from neutrophils, was shown to react with C3 at an epitope localized on the alpha-chain of C3. F(ab)2-fragments of M522 stimulate the respiratory burst of neutrophils and monocytes. M522 differs from two monoclonal antibodies against the Mo-1 molecule with respect to the capacity to inhibit the binding of sheep erythrocytes coated with different C3-fragments to C-receptor carrying cells. It inhibited the binding of H-coated particles to B-lymphoid cells and precipitated a 50,000 MW molecule from RAJI cells and tonsil lymphocytes. The results obtained suggest an antigenic relationship between the alpha-chain of C3, the heavy chain of a membrane molecule involved in neutrophil/monocyte activation, and a B-cell molecule of MW 50,000. PMID- 2579900 TI - Immunoglobulin subclass distribution of human anti-carbohydrate antibodies: aberrant pattern in IgA-deficient donors. AB - The IgG and IgA subclass distribution of anti-carbohydrate antibodies in normal and immunodeficient donors was investigated. In normal donors, the specific anti dextran antibodies were mainly of the IgG2 and IgA2 subclass, although substantial amounts of antibodies could also be of the IgG1 subclass. In children, IgG1 was the predominant subclass expressed. An aberrant IgG subclass distribution pattern of specific antibodies occurred in some IgA-deficient donors, with preferential expression of IgG1 and IgG3 anti-dextran antibodies. PMID- 2579902 TI - Effect of exercise on cation transport in human red cells. AB - To test the hypothesis that environmental as well as genetic factors are important determinants of monovalent cation transport systems in humans, and to explore potential basic mechanisms of the alleged antihypertensive effects of habitual exercise, we studied the effects of a 12-week exercise program (45 minutes, 3-5 times per week) upon several membrane transport parameters in erythrocytes from a population of 63 adult men (30 normotensive subjects and 33 essential hypertensive patients). Subjects were randomly assigned into either an exercise group or a sedentary control group, and clinical and membrane transport parameters were measured at baseline and after 3 months. Exercising subjects demonstrated increases in maximal treadmill work capacity (p less than 0.001) and high-density lipoprotein cholesterol levels (p = 0.009) as well as decreases in heart rate at a fixed submaximal workload (p less than 0.05) and body weight (p less than 0.001) relative to the sedentary group. In conjunction with these well described effects of exercise conditioning, the exercise group demonstrated a significant decrease in Na+-Li+ countertransport (p = 0.002), without significant changes in any other transport parameters measured. Blood pressure was not significantly altered in either group. We conclude that powerful environmental influences such as exercise training may act in concert with genetic factors to influence monovalent cation transport in humans and must be considered in further investigations of the pathophysiological linkage between altered monovalent cation transport and essential hypertension. PMID- 2579901 TI - IEF patterns of HLA-B13 antigens from Orientals and Caucasians. AB - HLA-B13 antigens were isolated from metabolically labeled cell extracts from Caucasian and Oriental donors by means of an HLA-B13-specific monoclonal antibody, SY1. Ethnic differences in B13 molecules were identified by one dimensional isoelectric focusing in which the pI of desialated Oriental B13 molecules was found to be higher than that of Caucasians. An additional Caucasian variant pattern was detected by peptide mapping using limited proteolysis in sodium dodecyl sulfate analyzed by polyacrylamide gel electrophoresis. Dual allotypic determinants for B13 molecules were recognized by two HLA-B13-specific monoclonal antibodies, SY1 and Tu110, as determined by their sensitivity to complement-dependent cell lysis. Whereas the SY1 target epitope was shared by both ethnic B13 molecules, the two ethnic B13 molecules carried different Tu110 target structures. The Caucasian variant molecules appear to carry altered allotypic determinants which are recognized by both SY1 and Tu110 antibodies. This study suggests that the HLA-B13 private structure may comprise two epitopes recognized by SY1 and Tu110 antibodies, respectively, whose binding sites overlap. Present data also suggest that the private determinant was already present when the two racial groups diverged, and thus the mutations which gave rise to the variants may be of relatively recent origin. PMID- 2579903 TI - Effect of glandular kallikrein on renin release in isolated rat glomeruli. AB - Numerous studies have suggested that a functional relationship may exist between the kallikrein-kinin and the renin-angiotensin systems within the kidney. We investigated the effects of glandular kallikrein on renin release by using an in vitro preparation of isolated rat glomeruli with their attendant arterioles. The effect of kallikrein was studied in the presence or absence of 0.1% bovine serum albumin (BSA) in Krebs superfusion fluid. We also studied the effect of inactivating kallikrein by treatment with phenylmethylsulfonyl fluoride or by inhibiting it with aprotinin. In the absence of BSA, kallikrein caused a 12-fold increase in renin release, from 5.1 +/- 1.2 ng angiotensin I (ANG I)/min to 66.0 +/- 2.27 ng ANG I/min (p less than 0.025). In the presence of BSA, renin release increased twofold, from 13.0 +/- 1.8 ng ANG I/min to 24.3 +/- 4.8 ng ANG I/min (p less than 0.025). The basal level of renin measured when the glomeruli were superfused with BSA-Krebs was two to three times greater than when they were superfused with Krebs alone (p less than 0.001). This finding suggests that media protein inhibited renin loss during either the superfusion or storage of renin samples. Neither phenylmethylsulfonyl fluoride-inactivated nor aprotinin inhibited kallikrein stimulated renin release. We propose that kallikrein can stimulate renin release in isolated glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579904 TI - Effect of the protease inhibitor aprotinin on renal hemodynamics in the pig. AB - Aprotinin, the serine protease inhibitor that also inhibits glandular (urinary) kallikrein, or vehicle was infused into the aorta above the renal arteries of anesthetized pigs. Renal hemodynamic and functional parameters were followed over time and during hemorrhagic hypotension. Both renal cortical blood flow and glomerular filtration rate were maintained in vehicle-treated animals at mean arterial pressures as low as 70 mm Hg. As long as renal cortical blood flow and glomerular filtration rate were maintained during the progressive hypotension, urinary excretion rate of kallikrein (as defined by kinin-generating activity) was increased. In contrast, all aprotinin-treated animals had a decreased excretion rate, and the renal cortical blood flow declined with the mean arterial pressure during hemorrhage. The pattern of glomerular filtration rate and plasma renin activity was comparable in both aprotinin-treated and vehicle-treated hemorrhaged animals. Our findings suggest that the endogenous renal kallikrein kinin system is required for functional renal vasodilatation to maintain renal cortical blood flow during hemorrhage and is therefore directly or indirectly responsible for adjustment of preglomerular resistance. PMID- 2579905 TI - Interaction of vasopressin and prostaglandins through calcium ion in the renal circulation. AB - To determine whether the effects of arginine vasopressin (AVP) on the renal and systemic vessels are modulated by prostaglandins (PGs), AVP (10, 20, and 50 mU/kg/min) was infused into the renal artery before and after treatment with indomethacin (8 mg/kg) in anesthetized rabbits. Arginine vasopressin elicited a dose-dependent increase in systemic arterial pressure and renal vasoconstriction. However, after cessation of the infusion, significant renal vasodilation was observed. Indomethacin potentiated the systemic and renal vasoconstrictor actions and attenuated the renal vasodilator reaction induced by AVP. These results suggest that endogenously produced PGs buffer the vasoconstrictor action of AVP, and the renal vasodilator reaction induced by AVP could be mediated through PGs. Further, to investigate whether the effects of AVP on the systemic and renal vessels are mediated by calcium ion (Ca++), the Ca++ entry blocker nifedipine was used. Intravenous administration of nifedipine (50 micrograms/kg) attenuated the systemic and renal vasoconstrictor action of AVP. The renal vasodilator reaction induced by AVP was also diminished after treatment with nifedipine. These results indicate that the systemic and renal vasoconstrictor actions of AVP are mediated through Ca++ influx into the vascular smooth muscle cells. The present study suggests that Ca++ participates in the AVP-induced vasodilator reaction, itself probably mediated by PGs. PMID- 2579906 TI - Increased membrane permeability of skin fibroblasts from the spontaneously hypertensive rat. AB - Recently, we have demonstrated several abnormalities in Na+ and K+ homeostasis in cultured vascular smooth muscle cells derived from spontaneously hypertensive rats (SHR). To study whether similar defects can be identified in other cells of this rat strain, 86Rb and 22Na flux experiments as well as measurements of intracellular Na+ and K+ levels were performed in cultured skin fibroblasts of SHR and normotensive Wistar-Kyoto rats (WKY). The efflux rate constant (ke) for Rb+ (K+ analogue) was higher (p less than 0.001) in fibroblasts of SHR than in those of WKY (2.11 +/- 0.03 and 1.66 +/- 0.02 X 10-2/min; mean +/- SEM). The ouabain-insensitive influx rate constant (ki) for Rb+ was also higher (p less than 0.001) in fibroblasts of SHR than in those of WKY (13.26 +/- 0.41 and 10.71 +/- 0.27 X 10-2/min. On the other hand, the activity of the Na+-K+ pump of cells of SHR (44.81 +/- 0.81 X 10-2/min) was not different from that of cells of WKY (44.72 +/- 0.47 X 10-2/min). This parameter was obtained by calculating the ouabain-sensitive Rb+ influx rate constant. There was also no difference in the Na+ uptake (in the presence of ouabain) between cells of the two rat strains. Although there was no statistically significant difference in the measured intracellular total K+ levels between the two groups, on the basis of equilibrium distribution of 86Rb+, we calculated a significantly lower (p less than 0.001) level of exchangeable intracellular K+ in fibroblasts of SHR (98.2 +/- 1.2 mEq/L) as compared with cells of WKY (115.3 +/- 1.5 mEq/L). These findings indicate increased membrane permeability to K+ in fibroblasts of SHR and that this defect is likely to be innate to their membrane structure. PMID- 2579909 TI - [Palliative care. A new mentality]. PMID- 2579907 TI - Acute-phase response of plasma protein synthesis during experimental inflammation in neonatal rats. AB - The pattern of plasma protein concentrations in neonatal rats differs characteristically from that in adult animals. Immediately after birth, the concentration of alpha 2-macroglobulin is about 200 times higher, that of major acute-phase alpha 1-protein the same, and that of alpha 1-acid glycoprotein, another acute phase protein, is considerably lower, compared with the values observed in healthy adults. The concentration of prealbumin, a negative acute phase protein, remains low in the immediate postnatal period, but increases at a time when concentrations of both thyroxine and corticosterone increase. At this time, there is also a distinct increase in the concentration of alpha 1-acid glycoprotein. Despite the differences in concentration of plasma proteins in the adult rat and the neonate, the neonatal liver has the capability to respond to an acute inflammation with a coordinated change in the synthesis rates of plasma proteins similar to that observed in adult animals. PMID- 2579908 TI - Expression of protective and cardiac tissue cross-reactive epitopes of type 5 streptococcal M protein in Escherichia coli. AB - The immunochemical properties of type 5 M protein antigens that were expressed in Escherichia coli K-12 by recombinant lambda bacteriophages isolated from a gene bank of serotype 5 Streptococcus pyogenes have been analyzed in detail. M proteins from partially purified bacteriophage lysates displayed precipitin lines of identity with a purified peptic extract of type 5 M protein (pep M5) in immunodiffusion assays. Immunoblot analyses of the M protein-positive lysates demonstrated that the cloned M protein component resided in five polypeptides with relative molecular weights of 57,900 (57.9K), 55.4K, 52.9K, 40.0K, and 32.6K. The hybrid lambda phage (lambda M5)-produced M protein contained immunoprotective epitopes; lambda M5 protein inhibited opsonization of type 5 streptococci by pep M5 antibodies, and antiserum raised against lambda M5 lysates opsonized type 5 streptococci. Each of the five antigenic polypeptides of the recombinant phage M protein also shared epitopes with human heart tissue, as demonstrated by the reactivity of immunoblots of lambda M5 antigens separated on sodium dodecyl sulfate gels with anti-pep M5 antibodies absorbed to and eluted from human heart sarcolemmal membranes. Moreover, antiserum raised against the lambda M5 lysates reacted with sarcolemmal membrane proteins with relative molecular weights of 200K, 59K, 55K, 53K, and 27K as determined by immunoblot analyses. These results demonstrate that the structural gene coding for type 5 streptococcal M protein which was inserted into lambda DNA expresses immunoprotective epitopes, some of which are shared with human heart tissue. PMID- 2579910 TI - Effect of perfluorochemicals on host defense, especially on the reticuloendothelial system. PMID- 2579911 TI - Relationship between specific circulating IgE, basophil cell-bound IgE and histamine release induced by purified allergens of Dermatophagoides farinae. AB - In this study we analysed the presence and proportions of IgE specific for Df 6 and Df 11, two purified allergens of Dermatophagoides farinae. The characterisation of serum IgE and cell-bound IgE for 3 D. farinae-sensitive patients were performed by CRIE, RAST and PRIST assays. Furthermore the basophils from these same patients were studied by histamine release assays in the presence of Df 6 and Df 11. All the individual patient's cell and serum IgE samples displayed the presence of IgE antibodies specific for Df 6 and Df 11, but the relative quantities of the IgE for these two specificities were characteristic of each patient. The ratios (Specific IgE for Df 11) : (Specific IgE for Df 6) (ratio 11 : 6) were similar in the serum and on the cells for an individual patient. As judged by histamine release assays, the basophil sensitivities towards Df 6 and Df 11 were very different from one atopic patient to another. Moreover cell sensitivities reflected the proportion of Df 6- and Df 11-specific IgE antibodies found in the serum and in the cell eluate. PMID- 2579912 TI - Interferon in experimental autoimmune encephalomyelitis (EAE): effects of exogeneous interferon on the antigen-enhanced adoptive transfer of EAE. AB - The transfer of experimental autoimmune encephalomyelitis (EAE) can be enhanced by incubating lymph node cells (LNC) from EAE rats with myelin basic protein (MBP). Addition of rat fibroblast interferon (RfIFN) to cultures of EAE-LNC just before the addition of MBP, resulted in the inhibition of the adoptive transfer of EAE. Both development of clinical signs, such as weight loss and hind limb paralysis, and histopathological lesions, lymphocytic perivascular infiltrates of the central nervous system, were inhibited by the addition of RfIFN to a final concentration of 300 U/ml or higher. This inhibition was dose dependent and appeared to be mediated primarily by the antiproliferative action of RfIFN. PMID- 2579914 TI - Suppression of murine IgE responses with amino acid polymer/allergen conjugates. I. Preparation of poly-(N-methylglycine)/grass pollen extract conjugates using 4 (methylmercapto)phenyl-succinimidyl succinate as coupling reagent. AB - A procedure utilising the latent activating potential of the 4 (methylmercapto)phenyl ester group has been developed for the controlled, reproducible preparation of macromolecular conjugates. This ester, as part of a succinyl-bridging group, was used to couple the water-soluble, amino acid polymer, poly-(N-methylglycine) (polysarcosine), via its N-terminal secondary amine, with the nucleophilic components of the aqueous extract of a mixture of grass pollens. The products exhibit a reproducible, antigen-specific suppressive effect on the in vivo synthesis of IgE in mice. PMID- 2579913 TI - Inhibitability and enhanceability of basophil histamine release in asthmatic and normal subjects. AB - Circulating human basophils contain histamine, a potent mediator of inflammation. Previous in vitro studies have shown that histamine 'releasability' in asthmatic subjects differs from normal subjects but have not evaluated possible differences in the immunopharmacological control of the release of this mediator which might account for these differences. The purpose of the present study was to examine the immunopharmacologic control of basophil histamine release in 14 asthmatics and 10 normal subjects who were characterized by pulmonary function tests, allergic status (skin tests and serum IgE levels) and nonspecific airways reactivity to methacholine and histamine. Basophils were stimulated with anti IgE, and the inhibitory effects of the H2 agonist, dimaprit, and dibutyryl cyclic AMP (dbcAMP), as well as the enhancing properties of 5 hydroperoxyeicosatetraenoic acid (5-HPETE) and indomethacin on the modulation of histamine release, were investigated. Although no statistically significant differences were seen in the percent histamine release triggered by anti-IgE in these two groups, enhancement of histamine release by 5-HPETE was more consistent in the asthmatic subjects (10 of 10) than in control subjects (6 of 8). The percent increase in histamine release produced by 5-HPETE in asthmatic subjects averaged 3.9 +/- 1.3% using 0.03 micrograms anti-IgE/ml and 4.8 +/- 3.2% using 0.1 microgram anti-IgE/ml (p less than 0.002, Wilcoxon's signed rank test), and averaged 3.0 +/- 4.3 and 3.1 +/- 5.3%, respectively, in control subjects (p greater than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2579915 TI - Suppression of murine IgE responses with amino acid polymer/allergen conjugates. II. Suppressive activities in adjuvant-induced IgE responses. AB - Treatment with conjugates of polysarcosine and grass pollen allergen extracts efficiently suppressed the induction of IgE responses in mice. The suppressive activity was shown to be allergen-specific and required covalent linking of the polysarcosine. Inhibitory effects could be overcome by booster injections of native allergen when these were given 3-4 weeks after treatment with conjugates. Administration of conjugates had only marginal effects on established IgE responses. The variance of these results with those of other studies on IgE suppression and the suitability of murine models for investigating reaginic antibody suppression are discussed. PMID- 2579916 TI - A dramatic representation of immunological cooperative events. PMID- 2579917 TI - The role of basophils and mast cells in the pathogenesis of pulmonary diseases. PMID- 2579918 TI - Lidocaine, mexiletine and propafenone in the treatment of arrhythmias complicating myocardial infarction. A case report. AB - We describe a case of acute myocardial infarction complicated by atrial and ventricular arrhythmias in which it was possible to verify the effectiveness of lidocaine, mexiletine and propafenone. Intravenous administration of mexiletine was ineffective both on atrial and ventricular rhythm disturbances. The lidocaine therapy reduced ventricular ectopic frequency, but did not prevent the appearance of several paroxysms of atrial fibrillation. Intravenous infusion of propafenone, 11 micrograms/kg per min, after a 1 mg/kg i.v. bolus, immediately and completely suppressed atrial arrhythmias. The increase in infusion rate up to 22 micrograms/kg per min also suppressed ventricular ectopy. This dosage of propafenone did not provoke serious adverse effects in our patient. PMID- 2579919 TI - Therapeutic effect of human fibroblast interferon on premalignant lesions arising in oral mucosa. A pilot study. AB - Human fibroblast interferon (HuIFN-beta) was topically administered to 20 premalignant lesions histopathologically showing epithelial dysplasia such as leukoplakia and lichen planus which arose in the oral mucosa. HuIFN-beta was prepared in the water-soluble gel form containing 2% carboxymethylcellulose, 45% glycelin, 0.1 M citrate buffer (pH 4.5) and 0.2% SDS as stabilizing agents. This preparation was found to be effective for herpetic gingivostomatitis and zostal lesions arising along the intercostal nerve. Thus, the HuIFN-beta preparation (10(4) to 5 X 10(3) IU) was applied to the oral mucosal lesion for 1 h twice a week. The lesion with topical administration of HuIFN-beta was covered tightly with the mucosal bandage which was coated with carboxymethylcellulose, glycelin and CaCl2 on vinyl acetate matrix. The 14 oral lesions with erosion or ulcer formation accompanied by severe pain by touch, had complete remission after approximately 10 successive applications of this preparation. Although subjective symptoms such as irritation pain in the other 6 patients with severe hyperkeratotic lesion subsided, white coatings and streaks could not be completely removed by this therapy. No other side-effects excluding slight pain and reddish swelling which occurred intermittently during HuIFN-beta administration were observed. PMID- 2579920 TI - Prediction of the conformation and antigenic determinants of the V-sis viral oncogene product homologous with human platelet-derived growth factor. AB - In an extensive study involving unification of secondary structure prediction methods to predict peptide backbone angles, folding simulations, and interactive graphics we have calculated conformations for a 160 residue p28sis protein fragment. We demonstrate that the state of the art is sufficient to aid artificial vaccine design. PMID- 2579921 TI - Studies of peptide antibiotics. XLVI. Syntheses of gramicidin S analogs containing D-alpha,beta-diaminopropionic acid or alpha,beta-dehydroalanine. AB - A gramicidin S (GS) analog ([D-Dpr4,4'] GS) containing D-alpha,beta diaminopropionic acid (D-Dpr) in place of D-Phe at 4,4' positions was derived from [L-Orn(delta-formyl)2,2', D-Dpr(beta-Z)4,4']GS, which was synthesized by conventional method in solution. An analog [delta Ala4,4']GS was synthesized from [L-Orn(delta-Boc)2,2', D-Dpr4,4']GS through Hofmann degradation of the D-Dpr residues. Antimicrobial activities of these analogs were tested; [D-Dpr(beta Z)4,4']GS and [delta Ala4,4']GS showed high antimicrobial activities against Gram positive bacteria. [D-Dpr4,4']-GS showed an appreciable activity against Gram negative bacteria such as Escherichia coli. Four semigramicidin S (semiGS) analogs such as [delta Ala4]semiGS were synthesized; these had no antimicrobial activity. Analogs containing delta Ala residues were hydrogenated, and the formation of L-Ala or D-Ala residues was determined. The delta Ala residues in [delta Ala4,4'] GS were reduced to DL-Ala, and delta Ala in [delta Ala4]semiGS mostly to L-Ala. The relationships of the antimicrobial activity, CD curves and asymmetric hydrogenation to the structure were discussed. PMID- 2579922 TI - NH resonances of Ribonuclease S-peptide in aqueous solution. Low temperature n.m.r. study. AB - A detailed study of the NH resonances of Ribonuclease-S-peptide (1-19 N-terminal fragment of Ribonuclease A) has been carried out in H2O, pH 3.0, in the temperature range 1-31 degrees, and ionic strength 0-1 M. Individual assignments of all NH amide signals have been achieved by means of extensive double resonance experiments. The folding of S-peptide at low temperature has been monitored by examination of the several NH resonance parameters: first, the nonlinearity of chemical shift vs. temperature plots; second, the selective broadening observed for signals assigned to residues 3-13; and third, the decrease of 3JHNCH coupling constants belonging to this region of the polypeptide chain. All these results are in agreement with the formation of a folded structure at low temperature, which is similar to the one found for the S-peptide in the RNase S crystal. PMID- 2579923 TI - Specificity of antisera obtained to substance P and its C-terminal hexapeptide. AB - Synthetic fragments and analogs were used to characterize specificity of antisera to SP and SP6-11. [Tyr8] SP and [Lys6] SP6-11 were both used as radioiodinated ligands. The latter was conjugated with Bolton-Hunter reagents before labelling. In both systems, the C-terminal pentapeptide SP7-11 was the shortest fragment showing antigenic identity with Substance P molecule. Substitution of different amino acid residues in SP6-11 by His or Gly showed that all but Glu6 take part in the structure of the antigenic determinant. PMID- 2579924 TI - The occurrence of thermotolerance in non-proliferating rat hepatocytes in primary culture. AB - The occurrence of thermotolerance, induced by an initial heat treatment at 42 degrees C for 30 min, was studied in adult non-proliferating rat hepatocytes in primary culture. Heat treatment at 42 degrees C for 30 min did not affect cell morphology, cell attachment, Na+, K+ pump activity, K+ content and lactate dehydrogenase accumulation into the medium. In contrast, after exposure to 44 degrees C for 30 min a dramatic change in all these parameters was observed. However, of the cells, which remained attached to the substratum 24 h after treatment, Na+, K+ pump activity and K+ content appeared to be normal compared with untreated cells. Cells, pre-treated at 42 degrees C for 30 min, followed by incubation at 37 degrees C for 16 h, were found to be completely thermal resistant against heat treatment at 44 degrees C, as judged by cell morphology, detachment from the substratum, lactate dehydrogenase accumulation, Na+, K+ pump activity and K+ content. These results show that induction and development of thermotolerance can be studied in non-proliferating cells in primary culture. PMID- 2579925 TI - [Defects of interferon formation]. PMID- 2579926 TI - [Molecular aspects of influenza epidemiology]. PMID- 2579927 TI - Demonstration of the mucous layer of the tear film by electron microscopy. AB - The mucous layer on the ocular surface maintains the stability, spread, and coherence of the tear film and is essential for normal vision. In spite of its importance, the precise thickness and localization of mucus on the surface of the eye are not known because it is not preserved in conventional electron microscopic preparations. The authors used two different methods to show mucus on the guinea pig cornea and conjunctiva. First, the authors precipitated mucous glycoproteins by adding a quaternary ammonium compound, either cetylpyridinium chloride or hexadecyltrimethylammonium bromide, to aldehyde fixatives. This procedure stabilized the mucus over the goblet cells and adjacent epithelium, although the mucous layer was not preserved uniformly in other areas. Tannic acid intensely stained mucus precipitated by these methods and showed it to be 0.8 micron thick on the cornea and 1.4 micron thick on the conjunctiva. To confirm these results, the authors also prepared specimens of cornea and conjunctiva by freeze substitution. This technique preserved the mucus in a smooth, uninterrupted layer. The thickness of the mucus was somewhat variable; it measured 1.0 micron over the cornea and varied from 2.0 to 7.0 micron over the conjunctiva because of the greater irregularity of the tissue. The authors' results show that mucus constitutes a considerable part of the precorneal tear film and is thicker than was recognized formerly. PMID- 2579928 TI - Antigen nonspecific rejection of allogeneic skin implants in the anterior chamber of sensitized rats. AB - As expected, skin implants placed in the anterior chamber of the eye of rats systemically sensitized with alloantigen from the antigen specific (second party) donor implants are rapidly rejected, indicating that the anterior chamber offers no barrier to the efferent immune response. However, during our studies it was noted that antigen nonspecific (third party) skin implants placed in the anterior chamber of the eye of similarly sensitized rats were also rejected in accelerated fashion. In all of the donor-recipient rat strain combinations tested which were sensitized by orthotopic skin grafts, third party skin implants placed in the anterior chamber of the eye were rejected within 14 days. A similar rejection pattern was noted in the anterior chamber of rats that were sensitized by the foot pad injection of graded doses of RT1 incompatible spleen cells. Rats sensitized with mouse skin grafts also rejected RT1 histoincompatible allogeneic implants within the anterior chamber, a result not noted in rats sensitized with either dog, rabbit, or pig skin grafts. PMID- 2579929 TI - Ventricular fibrillation. A complication and hazard of transcatheter obliteration of the renal artery with absolute ethanol in dogs. AB - Selective renal artery embolization with absolute ethanol was performed without balloon occlusion in a series of 11 healthy mongrel dogs. Electrocardiogram, blood ethanol level, heart rate, and blood pressure of the aorta and pulmonary artery were monitored. Ventricular extrasystoles and/or ventricular fibrillation occurred in six of the 11 dogs, to which absolute ethanol in doses ranging from 0.09 to 0.40 ml/kg was administered. In three of these six animals, the electrocardiograms showed only ventricular extrasystoles after intra-arterial bolus injection of absolute ethanol at doses of less than 0.15 ml/kg and subsequent recovery to a normal sinus rhythm. Ventricular fibrillation subsequent to ventricular extrasystoles immediately after intra-arterial injection of absolute ethanol at doses of more than 0.18 ml/kg occurred in three. In five of eight dogs that survived after alcohol injection in this series, a severe hypertensive response was observed. Absolute ethanol has the potential hazard of causing ventricular arrhythmia. Thus, careful observations should be undertaken in clinical therapeutic application of this agent, particularly in the absence of balloon occlusion, absolute ethanol should never be used without monitoring the electrocardiogram. PMID- 2579930 TI - Collateral arterial formation. Lymph draining ischemic kidneys contains a neovascular stimulating agent of high molecular weight. AB - An agent has been identified in lymph from rat kidneys rendered ischemic by partial renal artery occlusion that induces a striking neovascular response in a hamster cheek-pouch assay system. The factor has a high molecular weight, cannot be identified in lymph from normal kidneys, and is associated with a marked increase in vascularity and in endothelial cell turnover in the cheek pouch employed for assay. This factor may play an important role in the production of the collateral arterial circulation found in the presence of renal artery stenosis and renal ischemia. PMID- 2579932 TI - The histochemistry of urea-unmasked glycosaminoglycans in the skin of the eel, Anguilla japonica. AB - In the connective tissues of the dermis and subcutis of the eel skin, the histochemistry of urea-unmasked glycosaminoglycans has been studied by means of combined staining and enzyme digestion procedures. The staining procedures employed were alcian blue (AB) pH 1.0, AB pH 2.5, aldehyde fuchsin (AF), periodic acid-Schiff (PAS), AB pH 2.5-PAS, high iron diamine (HID) and low iron diamine (LID) methods, whereas the enzymes used were Streptomyces and testicular hyaluronidases, chondroitinases ABC and AC and keratanase. The results obtained have shown that a substantial amount of dermatan sulfate and a relatively small amount of hyaluronic acid, chondroitin, chondroitin sulfate A and/or C were the glycosaminoglycans involved in the connective tissues of the eel skin and that the tissues were devoid of keratan sulfate. PMID- 2579931 TI - beta-D-N-acetylglucosaminidase, a new cytochemical marker of human lymphocyte subpopulations. AB - beta-D-N-acetylglucosaminidase staining characteristics of rosetted or non rosetted normal and malignant lymphoid cells were compared with those observed after nonspecific esterase and acid phosphatase staining. With the three cytochemical techniques a similar staining pattern was observed in T cells (E rosettes), their subpopulations T mu and T gamma, B cells and the non-T, non-B cells, as well as in the T cell populations defined with the monoclonal antibodies OKT3,4 and 8. T mu cells mostly displayed a "dot-like" reaction, T gamma and the non-T, non-B cells a "fine to heavy granular" reaction, while most B cells were negative. OKT4 and OKT8 positive lymphocytes showed for the larger part a dot-like staining pattern, however, the frequency of cells with a granular pattern was distinctly higher in the OKT8, than in the OKT4 positive cells. E(+)mIg(-) and E(-)mIg(-) A.L.L. blasts stained either with a dot-like or granular pattern or failed to react when stained cytochemically for beta-D-N acetylglucosaminidase, nonspecific esterase and acid phosphatase activity. Only in a few instances a discrepancy was observed between the types of staining for esterase and acid phosphatase on one hand and those for beta-D-N acetylglucosaminidase on the other. PMID- 2579933 TI - Suggestive evidence for a functional unit between mast cells and substance P fibers in the rat diaphragm and mesentery. AB - A close spatial relationship between serotonin-containing mast cells and substance P-containing nerves was shown by immunohistochemistry using a combination of antisera specific for serotonin and substance P. This supports earlier morphological results suggesting an innervation of mast cells and pharmacological studies which postulate an influence of substance P on the release of histamine from mast cells. PMID- 2579936 TI - [Hyperreflectoric rhinopathy]. AB - Research in molecular biology in the past few years offers new views on vasomotor rhinitis. The key role of mediator substances which contain the mast cell and which, after degranulation, are active immediately by histamine release or act in a delayed manner (eg. leucotriene), is discussed, as well as the "liberofunction" of the neurotransmitter acetylcholine. The contribution to vasomotor rhinitis of other humoral systems, the kinine system and complement factors are also taken into account. The biopharmacological actions of the effector systems of the nasal mucosa (vessels, exocrine glands, nociceptors) are also analyzed. Using clinical examples the differentiation between humoral or neural reflex mediated hyperreflexia is worked out related to the classic triad of sneezing, profuse nasal discharge, nasal obstruction. The causes of vasomotor rhinitis (exogenous endogenous and drugs) are examined in the light of their pathophysiological importance. The differential diagnosis must cover allergic rhinopathy as well as the different kinds of rhinitis medicamentosa, the most important of which are discussed. Drugs which can help are discussed as well as continuous physical therapy. PMID- 2579935 TI - Automatic determination of labeling density in protein A-gold immunocytochemical preparations using an image analyzer. Application to peroxisomal enzymes. AB - The application of an automatic image analyzer (TAS, Leitz, Wetzlar) for determination of labeling density in protein A-gold labeled sections is described. Electron micrographs of rat liver labeled with 12 nm gold particles for peroxisomal enzymes are placed on the macrounit of TAS and the images of peroxisomes on TAS-monitor are contoured with a light pen. The instrument measures the surface of the contoured areas. Based on their gray level, the gold particles over the peroxisome are detected automatically and counted and the labeling density for each peroxisome is calculated. PMID- 2579934 TI - [Hydrophobic acridine dyes for fluorescent staining of mitochondria in living cells. 3. Specific accumulation of the fluorescent dye NAO on the mitochondrial membranes in HeLa cells by hydrophobic interaction. Depression of respiratory activity, changes in the ultrastructure of mitochondria due to NAO. Increase of fluorescence in vital stained mitochondria in situ by irradiation]. AB - The hydrophobic fluorescence dye 10-n-nonyl-acridinium-orange-chloride, NAO, stains specifically the mitochondria of living HeLa-cells. A dye concentration of 1 X 10(-8) M is sufficient for vital staining and at 5 X 10(-7) M an incubation time less than 1 min is enough to generate the bright green fluorescence of the mitochondria. The retention of NAO by the mitochondria is longer than 7 days. The dye accumulation is not affected by the ionophores valinomycin, nigericin, gramicidin, the uncoupling agents DNP, CCCP or by ouabain. In contrast to Rh 123 the trans-membrane potential is not the driving force of the NAO accumulation. We assume that NAO is bound to the hydrophobic lipids and proteins in the mitochondrial membranes by hydrophobic interaction. With valinomycin, 500 ng/ml, 10 min, the mitochondria in HeLa-cells swell. Now it is possible to observe some details in the enlarged mitochondria by light microscopy. After vital staining with NAO, 5 X 10(-7) M, 10 min, the periphery of the swollen mitochondria shows an intense green fluorescence, the inner part is dark. Obviously the dye is bound to the membranes. By electron microscopy it can be shown that the valinomycin treated and NAO stained mitochondria have outer and inner membranes and cristae. They differ from untreated mitochondria mainly in the size. After incubation of the HeLa-cells with relatively high NAO concentrations, 5 X 10(-6) M, 10 min, the mitochondria show a weak orange fluorescence. It is generated by the dimers D of NAO. Therefore the dye concentration in the mitochondrial membranes is locally very high and causes dye dimerisation. The weak orange fluorescence is instable and disappears within a few seconds. Instead we observe a green fluorescence with growing intensity that is generated by the monomers M of NAO. The intensity has its maximum value after a few seconds. Using low NAO concentrations for incubation, 1 X 10(-7) M, 10 min, we observe only the green fluorescence with increasing intensity. In this case the orange fluorescence is too weak for observation (concentration quenching). It can be shown by experiments and quantum mechanics that the orange fluorescence is assigned to an optical forbidden, the green fluorescence to an allowed electronic transition of D or M respectively. Our results indicate a dissoziation of D in 2 M by irradiation of the mitochondria under the fluorescence microscope.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2579937 TI - The molecular specificities of DS-specific reagents: an MB3-like monoclonal antibody isolates two DS molecules. AB - HLA-DS molecules are the human homologues of murine I-A molecules. The molecular specificities of four anti-DS reagents were examined by two-dimensional gel electrophoresis in light of the recent evidence that HLA-DR homozygous cell lines express at least two DS molecules. Each of the DS-specific reagents, including the IVD12 monoclonal antibody which defines an MB3-like determinant, isolated at least two DS molecules from a DR5 homozygous cell line. Because previous studies of this cell line documented that anti-MB3 allosera isolated only one DS molecule, these data indicate that there is heterogeneity of the molecular specificities of anti-Ia reagents that are specific for the MB3 allodeterminant or the MB3-like determinant in population studies. PMID- 2579938 TI - Palliative radiotherapy for inoperable carcinoma of the lung: final report of a RTOG multi-institutional trial. AB - Between June 1973 and February 1979, 409 patients with inoperable advanced non oat cell carcinoma of the lung were randomized on RTOG protocol 73-02. Three treatment arms were evaluated: 40 Gy split course, 30 Gy continuous course, and 40 Gy continuous course. Patients were also randomized to receive cytoxan or no further therapy following irradiation. Three hundred sixteen patients were evaluable. Palliation of symptoms was achieved in 60% with 1/4 of the patients becoming symptom-free. Complete regression of local and regional tumor was produced in 15% and partial regression in 26%. There is no significant difference between the treatment arms in these objective response rates. Median survival times were approximately 6 months. No significant benefit was demonstrated by the adjuvant use of Cytoxan. Although the number of complete responses produced was relatively small, patients achieving a complete response had a significantly longer median survival than the remaining patients, i.e., 14.5 months versus 6 months. Significant toxicity occurred in fewer than 6% of patients. Radiation pneumonitis counted for the majority of these adverse reactions. Toxicity occurred somewhat more often in the group treated with 40 Gy split course therapy. Implications for further studies are discussed. PMID- 2579939 TI - New gene in Escherichia coli K-12 (drpA): does its product play a role in RNA synthesis? AB - The mutation drpA1 defines a new gene in Escherichia coli K-12 that maps at about 5.2 min. This mutation was obtained after enriching a population of cells for temperature sensitive dna mutations with the [3H]thymidine "suicide" technique followed by screening for mutants defective in transposon Tn5 precise excision. When growing cells carrying the drpA1 allele were shifted to the nonpermissive temperature, we showed that DNA, RNA, and protein syntheses shut off quickly, with the cessation of RNA synthesis occurring first. A recombinant plasmid between pBR322 and an HindIII fragment from wild-type E. coli restores the growth defect in drpA1 mutants. Using transposon Tn5 mutagenesis of this plasmid, we have been able to correlate the presence of a 68-kilodalton protein, as observed with the maxicell technique, with the ability of this plasmid to restore growth to drpA1 mutants. PMID- 2579941 TI - Effect of DNA gyrase inactivation on RNA synthesis in Escherichia coli. AB - The average chain growth rates of rRNA and of total RNA were not affected by a thermal inactivation of DNA gyrase in a temperature-sensitive gyrB mutant of Escherichia coli. The fact that total RNA synthesis decreased under these conditions suggests that transcription is primarily affected at the step of chain initiation. The fraction of rRNA in total pulse-labeled RNA was not altered by inactivation of the enzyme, indicating that the latter is not required to actively maintain a high rate of synthesis of this RNA species. PMID- 2579940 TI - Cloning and characterization of the hemolysin determinants from Vibrio cholerae RV79(Hly+), RV79(Hly-), and 569B. AB - The Hly region from the chromosome of Vibrio cholerae El Tor strain RV79(Hly-) and the nonhemolytic classical strain 569B were cloned into plasmid vector pBR322. Escherichia coli K-12 transformants possessing these recombinant plasmids were nonhemolytic and were detected with a 32P-labeled hly-specific DNA probe. Restriction endonuclease Sau3AI digestions of the cloned hly loci of two independently obtained RV79(Hly+) convertants, when compared with the digests of cloned RV79(Hly-) loci, revealed that an apparent alteration (10 to 15 base pairs) had occurred. In contrast, an apparent 20-base-pair deletion was present in the cloned hly locus of the classical biotype V. cholerae strain 569B. Maxicell analysis and immunoprecipitation of labeled proteins of E. coli which are encoded by the cloned hly loci of RV79(Hly+) and from nuclease BAL 31-deleted plasmids, as well as immunoprecipitation of [35S]methionine-labeled V. cholerae proteins, suggest that the hemolysin is an 84,000-dalton polypeptide. PMID- 2579943 TI - Photoaffinity labeling of components of the apamin-sensitive K+ channel in neuronal membranes. AB - An azidonitrophenylaminoacetyl mono[125I]iodoapamin derivative was prepared which showed specific binding to rat neuronal membranes. UV photolysis lead to the irreversible occupation of binding sites. Photo-labeling of intact primary cultured rat neurones followed by membrane solubilization, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and autoradiography revealed the covalent incorporation of radioactivity into 3 main components with Mr = 86,000, 30,000, and 23,000. Labeling was completely prevented by a competing excess of native apamin. Similar studies on purified synaptic membranes from the rat brain showed another labeling pattern with major bands corresponding to Mr = 86,000 and 59,000. Although the reasons for the partial discrepancy between cultured embryonic neurons and an adult brain membrane fraction are not yet clear, we conclude that these proteins are intimately associated with the apamin binding site and are probably components of a type of Ca2+-activated K+ channel. PMID- 2579942 TI - Purification of Legionella pneumophila major outer membrane protein and demonstration that it is a porin. AB - We have purified the major outer membrane protein (MOMP) of Legionella pneumophila, determined that it is associated with peptidoglycan, and characterized it as a porin. To purify the MOMP, we used a simple, rapid, three step procedure that gave us the protein in high yield. The first step of the purification procedure involved selectively extracting the MOMP from whole bacterial cells with calcium and zwitterionic detergent. The second and third steps achieved purification by ion-exchange and molecular-sieve chromatography. The dissociation of the MOMP into monomers was dependent upon the presence of a reducing agent and was enhanced by treatment at 100 degrees C. To study the relationship of the MOMP to peptidoglycan, we extracted the protein by a modification of the Rosenbusch procedure. Like the Escherichia coli porins, the MOMP was peptidoglycan associated. The MOMP was at least partially dissociated from peptidoglycan in sodium dodecyl sulfate and a high salt concentration. To study the ion channel-forming properties of the MOMP, we reconstituted the MOMP in planar lipid membranes. The MOMP formed ion-permeable channels with a single channel conductance size of 100 picoSiemens. The MOMP channels exhibited a fourfold selectivity for cations over anions and voltage-independent gating. These findings demonstrate that the MOMP is a porin with properties similar to those of E. coli porins. PMID- 2579944 TI - Formation of highly stable complexes between 5-azacytosine-substituted DNA and specific non-histone nuclear proteins. Implications for 5-azacytidine-mediated effects on DNA methylation and gene expression. AB - Incubation of 5-azacytosine-substituted DNA ([5-aza-C]DNA) with nuclear proteins leads to the formation of highly stable DNA . protein complexes which remain intact in the presence of 1 M NaCl and/or 0.6% Sarkosyl. The proteins involved in binding double-stranded [5-aza-C]DNA in these stable complexes comprise a specific subset of non-histone nuclear proteins that includes DNA methyltransferase. Complex formation does not require S-adenosylmethionine and does not involve covalent linkage of protein to DNA or modification of 5 azacytosine residues. Non-histone nuclear proteins do not form complexes with double-stranded unsubstituted DNA that are resistant to dissociation with NaCl and Sarkosyl but are capable of forming such complexes with single-stranded DNA regardless of whether it contains 5-azacytosine residues or not. However, it can be demonstrated 1) that single-stranded regions do not account for stable binding of proteins to native [5-aza-C]DNA and 2) that many nuclear proteins which form stable complexes with single-stranded DNA are incapable of forming such complexes with double-stranded [5-aza-C]DNA. Synthesis of [5-aza-C]DNA by cells growing in the presence of either 5-azacytidine or 5-aza-2'-deoxycytidine leads to rapid loss of extractable DNA methyltransferase (Creusot, F., Acs, G., and Christman, J.K. (1982) J. Biol. Chem. 257, 2041-2048). Analogous depletion of non-histone nuclear proteins capable of forming stable complexes with [5-aza-C]DNA in vitro is observed, suggesting that the same proteins can form highly stable complexes with [5-aza-C]DNA in vitro and in vivo. Formation of stable complexes between non histone nuclear proteins and [5-aza-C]DNA could potentially affect not only the activity of DNA methyltransferase but the action of other regulatory proteins or enzymes that interact with DNA. Such interactions could explain effects of 5 azacytidine on gene expression that cannot be directly linked to loss of methyl groups from DNA. PMID- 2579945 TI - The divalent cation dependence of bovine brain calmodulin-dependent phosphatase. AB - The divalent cation dependence of a calmodulin-stimulated phosphatase from bovine brain has been characterized kinetically using phosphorylated myelin basic protein and casein as substrates. At saturating concentrations of calmodulin, dephosphorylation of both myelin basic protein and casein was catalyzed 8- to 10 fold more rapidly at saturating concentrations of Mn2+ than at saturating concentrations of Ca2+. Half-maximal rates of dephosphorylation of both substrates occurred at either 15 microM Mn2+ or 1 microM Ca2+, and the Kact for each ion was not influenced appreciably by the presence of calmodulin. Half maximal rates of dephosphorylation were observed at concentrations of calmodulin ranging from 3 X 10(-8) to 10(-6) M at saturating concentrations of divalent cations depending on the substrate used and the particular cation chosen. Trypsin treatment of the phosphatase activated the enzyme several-fold, eliminated its calmodulin dependence, but did not alter the Mn2+ concentration dependence of the activity. Ca2+ (10 microM) increased dephosphorylation rates without altering the Mn2+ concentration dependence of the phosphatase activity regardless of the presence of calmodulin. Mg2+ at millimolar concentrations did not alter the Ca2+ or Mn2+ concentration dependence of the activity. As measured without calmodulin, Ca2+ (90 microM) or Mn2+ (200 microM) produced nearly identical alterations of the far ultraviolet circular dichroic spectrum of the phosphatase. PMID- 2579946 TI - Monoclonal antibodies as probes for functional domains in cAMP-dependent protein kinase II. AB - The antigenic regions of the type II regulatory subunit of cAMP-dependent kinase from bovine heart have been correlated with the previously established domain structure of the molecule. Immunoblotting with both serum and monoclonal antibodies of fragments generated by limited proteolysis or chemical cleavage of the R-subunit established that the major antigenic sites were confined to the amino-terminal portion of the polypeptide chain (residues 1-145). Radioimmunoassays using two different antisera suggested that one or more of the high affinity serum antibody recognition sites were further restricted to residues 91-145. This amino-terminal portion of the R-subunit includes the hinge region which is particularly sensitive to proteolysis, allowing the R-subunit to be cleaved readily into a COOH-terminal domain which retains the cAMP-binding sites and an NH2-terminal fragment which appears to be the major site for interaction of the R-subunits in the native dimer. Monoclonal antibodies that recognized determinants on both sides of this hinge region were characterized and their specific recognition sites localized. Accessibility of antigenic sites in the holoenzyme in contrast to free R2 was compared. Although cAMP did tend to slightly increase the affinity of the holoenzyme for one of the monoclonal antibodies, all of the antigenic sites clearly were exposed and accessible in the holoenzyme. Furthermore, despite the presumed close proximity of antigenic sites to interaction sites between the R- and C-subunits, in no case did binding of antibody to the holoenzyme promote dissociation of the complex. The fact that the monoclonal antibodies would precipitate holoenzyme as well as free R2 was used to ascertain the importance of specific amino acid residues in the interaction of the R- and C-subunits. cAMP-binding domains were isolated following limited proteolysis with chymotrypsin and thermolysin. These fragments differed by only three amino acid residues at the NH2-terminal end. U of these fragments in conjunction with immunoadsorption established that the chymotryptic fragment, which contained the Asp-Arg-Arg preceding the site of autophosphorylation, was capable of forming a stable complex with the C-subunit. In contrast, the thermolytic fragment which differed by only those three residues no longer complexed with the C-subunit, indicating that the arginine residues not only contribute to the specificity of the phosphorylation site but also are an essential component for energetically stabilizing the holoenzyme complex. PMID- 2579947 TI - Role of calcium and cAMP in the action of adrenocorticotropin on aldosterone secretion. AB - When the dose-response curve of adrenocorticotropin (ACTH)-induced aldosterone secretion is compared to that of ACTH-induced intracellular cAMP, the ED50 for intracellular cAMP is more than 10 times as high as that for aldosterone production. In contrast, the dose-response curve of forskolin-induced aldosterone secretion correlates well with that for forskolin-induced intracellular cAMP. ACTH, but not forskolin, increases calcium influx into glomerulosa cells without inducing the mobilization of calcium from an intracellular pool. The effect of ACTH on calcium influx is dose-dependent and ED50 is 3.5 X 10(-11) M. In a perifusion system, the effect of 1 nM ACTH on aldosterone secretion is much greater than that of 1 microM forskolin, even though these two stimulators induce identical increases in the intracellular cAMP. Perifusion with combined A23187 (50 nM) and forskolin (1 microM) stimulates aldosterone secretion to a value comparable to that induced by 1 nM ACTH. Likewise, BAY K 8644 (1 nM), which induces a comparable increase in calcium influx, potentiates the effect of 1 microM forskolin. When the intracellular [Ca2+] is fixed at either 100 or 300 nM, forskolin-stimulated intracellular cAMP content is identical, but ACTH-stimulated intracellular cAMP content at 100 nM [Ca2+]i is 60% of that at 300 nM [Ca2+]i. Both the ACTH- and forskolin-induced aldosterone secretion rate is higher at 300 nM than at 100 nM [Ca2+]i. These results indicate that ACTH stimulates calcium influx, that calcium potentiates ACTH-induced but not forskolin-induced cAMP generation, and that Ca2+ and cAMP act as synarchic messengers in ACTH-mediated aldosterone secretion. PMID- 2579948 TI - Distribution of plasma kallikrein between C-1 inactivator and alpha 2 macroglobulin in plasma utilizing a new assay for alpha 2-macroglobulin kallikrein complexes. AB - We have previously described an enzyme-linked immunosorbent assay for the quantification of C-1 inactivator-kallikrein complexes in plasma (Lewin, M. F., Kaplan, A. P., and Harpel, P. C. (1983) J. Biol. Chem. 258, 6415-6421). We have now developed an immunoimmobilization-enzyme assay for alpha 2-macroglobulin kallikrein complexes. In this assay these complexes are removed from plasma by immunoabsorption with the IgG fraction of rabbit anti-alpha 2-macroglobulin antiserum coupled to an agarose gel. The immobilized alpha 2-macroglobulin kallikrein complex hydrolyzes the fluorogenic substrate D-Ser-Pro-Phe-Arg-7-amino 4-trifluoromethyl coumarin, and this activity is proportional to the concentration of complexes in the plasma. Using these assays we have studied the distribution of plasma kallikrein between its inhibitors under several different experimental conditions. When kallikrein is added to plasma, about 57% binds to C 1 inactivator and 43% to alpha 2-macroglobulin. When prekallikrein is activated endogenously in plasma by the addition of kaolin or Hageman factor fragment, approximately 84% of kallikrein is now bound to C-1 inactivator and 16% to alpha 2-macroglobulin. Temperature dramatically affects the distribution of kallikrein. The binding of kallikrein to alpha 2-macroglobulin in plasma is inversely related to temperature, whereas the binding to C-1 inactivator is directly related: 85% of the kallikrein is bound to alpha 2-macroglobulin at 4 degrees C, whereas at 37 degrees C, only 33% is bound. The total amount of kallikrein bound to the two inhibitors is similar at each temperature. These studies thus provide new insight concerning kallikrein formation and regulation in plasma. PMID- 2579950 TI - Characterization of nine monoclonal antibodies against the Escherichia coli cyclic AMP receptor protein. AB - Nine hybridoma clones producing antibodies against the Escherichia coli cAMP receptor protein (CRP) have been isolated. Five of the monoclonal antibodies (Class I) had a much higher affinity for native CRP while the remaining four (Class II) bound equally well to native or denatured CRP. Using native N-terminal CRP cores, it was shown that none of the Class I monoclonal antibodies cross reacted with the 15,000-Da CRP core, and only two bound to the 18,800-Da CRP core. The positions of the antigenic determinants for the Class II monoclonal antibodies were found by Western blotting analysis to reside in the N-proximal region of CRP. Only one monoclonal antibody strongly inhibited cAMP binding by CRP, and this was accompanied by a consequent strong inhibition of both lac DNA binding and abortive initiation by RNA polymerase. Each of the Class I monoclonal antibodies inhibited abortive initiation, and four of these antibodies also blocked the binding of cAMP X CRP to the lac DNA fragment. One Class I and one Class II monoclonal antibody bound to the cAMP X CRP X DNA complex. Two of the Class II monoclonal antibodies were without apparent effect on any of the assays used. PMID- 2579951 TI - Nutritional regulation of the synthesis and degradation of malic enzyme messenger RNA in duck liver. AB - The amount of malic enzyme mRNA in total liver RNA increased rapidly when starved ducklings were fed a high-carbohydrate mash diet, reaching 15 times the initial level at 9 h and an apparent steady state, about 20 times the initial level, at 24 h. Based on the kinetics of accumulation, malic enzyme mRNA had a half-life of 3-5 h in the livers of fed ducklings. When fed ducklings were starved, malic enzyme mRNA decreased with a half-life of about 1 h. Feeding, therefore, may have inhibited the degradation of malic enzyme mRNA, but not sufficiently to account for the 20-fold increase in mRNA level. The level of malic enzyme sequences in nuclear RNA increased severalfold when starved ducklings were fed, consistent with a stimulation of transcription. The rate of transcription of the malic enzyme gene, as measured in isolated nuclei, increased 3-5-fold when starved ducklings were refed. Starvation of fed animals caused a 55-65% inhibition of the transcription of the malic enzyme gene. Synthesis of albumin mRNA was little affected by refeeding or starvation, indicating that the observed effects on synthesis of malic enzyme mRNA were selective. We conclude that both increased transcription and decreased degradation contribute to the 20-fold increase in malic enzyme mRNA caused by feeding starved ducklings. PMID- 2579949 TI - Isolation of cDNA and genomic clones encoding human pro-alpha 1 (III) collagen. Partial characterization of the 3' end region of the gene. AB - A cDNA library constructed from human fibroblast poly(A+) RNA was screened for the identification of chimeric molecules bearing collagen-specific sequences. Analysis of three of the resulting positive clones showed that they encoded for the COOH-terminal propeptide region of the human Type III collagen. In addition, three overlapping clones covering more than 21 kilobases of the Type III gene were isolated from Charon 4A libraries of human genomic fragments. Identity between these and the cDNA clones was obtained by direct DNA sequencing. Establishment of the exon/intron arrangement of the Type III gene was obtained by electron microscopic analysis in conjunction with sequencing of selected genomic regions. Sequence comparison with other collagen genes confirmed some evolutionary features of this important family of proteins. Finally, the collinearity of two mRNA transcripts with 3' noncoding region length polymorphism was established. PMID- 2579952 TI - Characterization of factors and DNA sequences required for accurate transcription of the Saccharomyces cerevisiae 5 S RNA gene. AB - Cell-free extracts prepared from yeast cells have previously been shown to direct selective and accurate in vitro transcription of tRNA and 5 S RNA genes. We have further analyzed the transcription factors and DNA sequences required for in vitro transcription of the yeast 5 S RNA gene. Fractionation of a yeast extract has identified a 5 S RNA gene-specific factor required, in addition to the two previously described tRNA factors (Klekamp, M. S., and Weil, P. A. (1982) J. Biol. Chem. 257, 8432-8441), for accurate transcription of the 5 S RNA gene by RNA polymerase III. Transcription of variant 5 S RNA genes has indicated that a region of the gene extending from residue +57 to residue +99 is essential for directing specific initiation of transcription. Although the 5' flanking and initial coding sequence is not absolutely required for transcription of the gene, some of the variant genes which have substitutions in this region are less actively transcribed than the wild-type gene. Transcription initiates on some of the variant genes at a position equivalent to +1 in the substituted sequence, while on other variant genes transcription initiates further upstream. PMID- 2579953 TI - Dextran/aspirin versus heparin/dihydroergotamine in preventing thrombosis after hip fractures. AB - In a randomised trial we compared the effects of two different antithrombotic regimens on the incidence of venographically established deep venous thrombosis (DVT) in 83 patients undergoing surgery for fracture of the femoral neck. Group A received dextran 40 peroperatively plus 0.5 g aspirin a day beginning before operation and continuing for 10 days after. Group B received heparin calcium 5000 iu subcutaneously plus dihydroergotamine (DHE) 0.5 mg intramuscularly, given 8 hourly, beginning before operation and continuing for 10 days after. Two patients in Group A and three in Group B developed proximal DVT, while the incidence of all DVT was 33% in Group A and 29% in Group B, a difference which was not significant. Haemorrhagic complications were much more common in the dextran/aspirin group: the volume of drainage fluid, the number of patients transfused and quantity of blood transfused, and the drop in haemoglobin level were all significantly greater in Group A. We conclude that the DHE/heparin regime is preferable to dextran/aspirin because it is safer and no less effective. PMID- 2579954 TI - Combined effect of 5-fluorouracil and interferon on experimental liver metastases of rat colon carcinoma. AB - The combined effect of 5-Fluorouracil (5-Fu) and partially purified rat interferon (RIFN) was assessed on experimental liver metastases of a transplantable colon tumor in rats. Treatment was given for 8 weeks and started 1 week after inoculation into the portal vein of 5 X 10(5) tumor cells. Administration of 10(5) units RIFN/kg/day for 7 days, in alternate weeks, had no effect on the number or size of liver metastases as judged by laparotomy on days 30 and 50, whereas treatment with 5-Fu at a dose of 15 mg/kg once a week had a moderate but significant inhibitory influence. The combined administration of RIFN and 5-Fu led to earlier development of liver metastases than in the control group. There was no difference in survival time between the control group and the RIFN-treated group; all animals died within 20 weeks after tumor cell injection. However, three of eight animals in the 5-Fu group and, surprisingly, four of ten animals in the RIFN + 5-Fu group survived for more than 20 weeks and were found to be free of tumor when inspected after 175 days. The data indicate that 5-Fu, given either alone or combined with RIFN, is effective in about 40% of cases, and further suggest that RIFN has tumor-enhancing properties in those animals in which treatment with 5-Fu has no antitumor effect. PMID- 2579955 TI - Monoclonal antibodies against seven sites on the head and tail of Dictyostelium myosin. AB - Ten monoclonal antibodies (My1-10) against Dictyostelium discoideum myosin were prepared and characterized. Nine bound to the 210-kD heavy chain and one (My8) bound to the 18-kD light chain. They defined six topographically distinct antigenic sites of the heavy chain. Five binding sites (the My1, My5, My10 site, and the My2, My3, My4, and My9 sites) are located on the rod portion of the myosin molecule. The position of the sixth site (the My6 and My7 site) is less certain, but it appears to be near the junction of the globular heads and the rod. Three of the antibodies (My2, My3, and My6) bound to myosin filaments in solution and could be sedimented in stoichiometric amounts with the filamentous myosin. In contrast, My4, which recognized a site on the rod, inhibited the polymerization of monomeric myosin into filaments. A single antibody (My6) affected the actin-activated ATPase of myosin. The nature of the effect depended on the valency of the antibody and the myosin. Bivalent IgG and F(ab')2 fragments of My6 inhibited the actin-activated ATPase of filamentous myosin by 50% whereas univalent Fab' fragments increased the activity by 50%. The actin-activated ATPase activity of the soluble chymotryptic fragment of myosin was increased 80 90% by both F(ab')2 and Fab' of My6. PMID- 2579956 TI - Proteins transported in slow components a and b of axonal transport are distributed differently in the transverse plane of the axon. AB - The distribution of the proteins migrating with the slow components a (SCa) and b (SCb) of axonal transport were studied in cross-sections of axons with electron microscope autoradiography. Radiolabeled amino acids were injected into the hypoglossal nucleus of rabbits and after 15 d, the animals were killed. Hypoglossal nerves were processed either for SDS-polyacrylamide gel electrophoresis fluorography to identify and locate the two components of slow transport, or for quantitative electron microscope autoradiography. Proteins transported in SCa were found to be uniformly distributed within the cross section of the axon. Labeled SCb proteins were also found throughout the axonal cross-section, but the subaxolemmal region of the axon contained 2.5 times more SCb radioactivity than any comparable area in the remainder of the axon. PMID- 2579957 TI - Glucocorticoids increase amylase mRNA levels, secretory organelles, and secretion in pancreatic acinar AR42J cells. AB - Previous studies have suggested a role for glucocorticoids in the differentiation of the acinar pancreas. We have now used the rat tumor cell line AR42J, derived from the acinar pancreas, to directly study this effect of glucocorticoids in vitro. The steroid hormones dexamethasone, corticosterone, aldosterone, and progesterone, but not estrogen, increased both the amylase content and the number of secretory granules of these cells. The potencies of the steroids were directly related to their effectiveness as glucocorticoids; dexamethasone was the most potent hormone and gave maximal effects at 100 nM. Morphometric analyses revealed that dexamethasone increased the volume density of granules 5.5-fold from 0.20 +/ 0.08 to 1.10 +/- 0.20% (n = 4) of the cytoplasmic volume. Dexamethasone treatment also increased the volume density of rough endoplasmic reticulum 2.4 fold from 1.20 +/- 0.09 to 2.86 +/- 0.30% (n = 5) of the cytoplasmic volume. After 48 h of dexamethasone treatment the cellular content of amylase increase eightfold from 2.8 +/- 0.4 to 22.6 +/- 3.8 U/mg protein (n = 6). This effect of dexamethasone was discernible after 12 h of incubation and approached maximal stimulation after 72 h of incubation. The increases in cellular amylase content were due to increased amylase synthesis as shown by specific immunoprecipitation of [35S]methionine-labeled proteins. Moreover, in vitro translation of cellular mRNA indicated that dexamethasone treatment increased amylase mRNA. Dexamethasone treatment also led to increased secretion of amylase in response to the secretagogue cholecystokinin. These data indicate, therefore, that glucocorticoids induce a more highly differentiated phenotype in AR42J pancreatic cells, and they suggest that glucocorticoids act via the enhanced transcription of specific mRNAs for acinar cell proteins. PMID- 2579959 TI - Topography of cell-glass apposition revealed by total internal reflection fluorescence of volume markers. AB - We have developed a new method based on total internal reflection fluorescence to map the shape of the region between glass and the lower surface of a living cell spread upon it. Fluorescently labeled nonadsorbing volume marker molecules that cannot penetrate into the cell are locally stimulated so that they fluoresce only very near the glass/medium interface. The total fluorescence intensity at any point beneath the cell depends on the cell-to-glass separation. Focal contacts appear as dark areas owing to dye exclusion, whereas when the gap exceeds approximately 150 nm, fluorescence asymptotes to the bright background level. Our technique provides greater contrast than does interference reflection microscopy and is free from errors due to cytoplasmic thickness and refractive index inhomogeneities arising from cytoplasmic inclusions. We have shown that sufficiently large molecules suffer steric exclusion from regions accessible to small molecules, which gives new information about lateral penetrability in the apposition region. PMID- 2579958 TI - Identification of a transmembrane glycoprotein specific for secretory vesicles of neural and endocrine cells. AB - Several types of cells store proteins in secretory vesicles from which they are released by an appropriate stimulus. It might be expected that the secretory vesicles in different cell types use similar molecular machinery. Here we describe a transmembrane glycoprotein (Mr approximately 100,000) that is present in secretory vesicles in all neurons and endocrine cells studied, in species from elasmobranch fish to mammals, and in neural and endocrine cell lines. It was detected by cross-reactivity with monoclonal antibodies raised to highly purified cholinergic synaptic vesicles from the electric organ of fish. By immunoprecipitation of intact synaptic vesicles and electron microscopic immunoperoxidase labeling, we have shown that the antigenic determinant is on the cytoplasmic face of the synaptic vesicles. However, the electrophoretic mobility of the antigen synthesized in the presence of tunicamycin is reduced to Mr approximately 62,000, which suggests that the antigen is glycosylated and must therefore span the vesicle membrane. PMID- 2579961 TI - Superinduction by cycloheximide of mitogen-induced secreted proteins produced by Balb/c 3T3 cells. AB - We describe here some of the characteristics of the regulation of a group of secretory proteins whose secreted levels rise within 2-4 h of adding fibroblast growth factor (FGF), epidermal growth factor (EGF), or serum to quiescent Balb/c 3T3 cells. The levels of these secretory proteins are regulated similarly to the interferons. When cycloheximide is present during the induction period, the amounts of [35S]methionine incorporated into five of these proteins that we have called "superinducible proteins" (SIPs) is increased 2-5-fold. Superinduction of the SIPs is seen also in response to polyribol-polyriboC, the classical inducer of interferons. None of the SIPs, however, are immuno-precipitated by anti-beta interferon antibody. Induction and superinduction of the SIPs is inhibited by actinomycin D. Superinduction occurs at concentrations of cycloheximide that inhibit protein synthesis by at least 85%. The SIPs are not major intracellular proteins; they are barely detectable in cellular fractions. Their induction is, however, correlated with the ability of the polypeptide growth factor to stimulate DNA synthesis; EGF, FGF, and serum induce the SIPs, whereas insulin does not, and insulin alone weakly stimulates DNA synthesis in these cells. Because FGF, EGF, and serum cause the SIPs to be produced at concentrations of cycloheximide that inhibit 85% of bulk protein and DNA synthesis, it follows that the SIPs are produced directly from the action of the growth factor and not as a consequence of increased growth. Although probably not interferons, in analogy to the lymphokines, the SIPs could be a set of autocrine or paracrine factors that rapidly convey the growth or differentiation signal between cells. PMID- 2579962 TI - Phospholipid asymmetry in human erythrocyte ghosts. AB - Using phospholipase digestion and the fluorescent probe merocyanine 540 the maintenance of phospholipid asymmetry in the plasma membrane of human erythrocyte ghosts was investigated. Digestion with phospholipase A2 indicated that ghosts prepared in the presence of Mg++ as the only divalent cation retained the normal phospholipid asymmetry characteristic of intact erythrocytes. These ghosts, like normal erythrocytes, also failed to stain with merocyanine 540. However, the presence of as little as 5-10 microM Ca++ during ghost preparation resulted in ghosts in which lipid asymmetry had been abolished, as indicated by phospholipase digestion. Moreover, these ghosts stained with merocyanine 540. In contrast to ghosts, intact erythrocytes treated with ionophore required millimolar levels of Ca++ ions to disrupt membrane lipid asymmetry. To discover the reason for this difference in behavior between ghosts and intact cells, ghosts were prepared from preswollen cells using only small volumes of buffer for lysis. These experiments demonstrated that as the cellular contents of erythrocytes are diluted, the asymmetric arrangement of phospholipids becomes more sensitive to disruption by Ca++. PMID- 2579960 TI - Intermediate filament cytoskeleton of amnion epithelium and cultured amnion epithelial cells: expression of epidermal cytokeratins in cells of a simple epithelium. AB - Using immunofluorescence microscopy and two-dimensional gel electrophoresis, we compared the cytoskeletal proteins expressed by human amnion epithelium in situ, obtained from pregnancies of from 10-wk to birth, with the corresponding proteins from cultured amnion epithelial cells and cultures of cells from the amniotic fluid of 16 week pregnancies. Epithelia of week 16 fetuses already display tissue specific patterns of cytokeratin polypeptides which are similar, although not identical, to those of the corresponding adult tissues. In the case of the simple amnion epithelium, a complex and characteristic complement of cytokeratin polypeptides of Mr 58,000 (No. 5), 56,000 (No. 6), 54,000 (No. 7), 52,500 (No. 8), 50,000 (No. 14), 46,000 (No. 17), 45,000 (No. 18), and 40,000 (No. 19) is present by week 10 of pregnancy and is essentially maintained until birth, with the addition of cytokeratin No. 4 (Mr 59,000) and the disappearance of No. 7 (Mr 54,000) at week 16 of pregnancy. In full-term placentae, the amnion epithelium displays two morphologically distinct regions, i.e., a simple and a stratified epithelium, both of which express the typical amnion cytokeratin polypeptides. However, in addition the stratified epithelium also synthesizes large amounts of special epidermal cytokeratins such as No. 1 (Mr 68,000), 10 (Mr 56,500), and 11 (Mr 56,000). In culture amnion epithelial cells obtained from either 16-wk pregnancies or full-term placentae will continue to synthesize the amnion-typical cytokeratin pattern, except for a loss of detection of component No. 4. This pattern is considerably different from the cytokeratins synthesized by cultures of cells from amniotic fluids (cytokeratins No. 7, 8, 18, and 19, sometimes with trace amounts of No. 17) and from several so-called "amnion epithelial cell lines." In addition, amnion epithelial cells in situ as well as amnion epithelial cell cultures appear to be heterogeneous in that they possess some cells that co express cytokeratins and vimentin. These observations lead to several important conclusions: In contrast to the general concept of recent literature, positively charged cytokeratins of the group No. 4-6 can be synthesized in a simple, i.e., one-layered epithelium. The change from simple to stratified amnion epithelium does not require a cessation of synthesis of cytokeratins of the simple epithelium type, but in this case keratins characteristic of the terminally differentiated epidermis (No. 1, 10, and 11) are also synthesized.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2579963 TI - Intracellular Ca2+ sequestration in cultured mouse fibroblasts: ATP-dependent Ca2+ uptake by saponin-permeabilized Swiss 3T3 cells. AB - Intracellular Ca2+ sequestration was studied by determining 45Ca2+ uptake by saponin-permeabilized Swiss 3T3 mouse fibroblasts. Uptake was enhanced by addition of ATP and was dependent on the concentrations of ATP and saponin. ADP and UTP also enhanced uptake, but less than did ATP. Mitochondrial Ca2+ uptake was distinguished from nonmitochondrial uptake by the use of antimycin A plus oligomycin at various Ca2+ concentrations. Major sites for sequestration at 10( 5) M Ca2+ are probably mitochondrial and those at 10(-7) M Ca2+ nonmitochondrial, because these drugs inhibited ATP-dependent Ca2+ uptake at 10(-5) M but not at 10(-7) M. A23187 completely inhibited uptake, regardless of the Ca2+ concentration. Effects of various agents on sequestration were tested; ruthenium red, 2,4-dinitrophenol, monovalent cation ionophores, and melittin markedly decreased ATP-dependent Ca2+ uptake at 10(-5) M Ca2+. The calmodulin antagonists trifluoperazine (TFP) and W-7 inhibited Ca2+ uptake at both 10(-5) and 10(-7) M Ca2+, TFP more so than W-7, especially at 10(-5) M. These results suggest that intracellular Ca2+ in Swiss 3T3 cells is regulated by mitochondrial and nonmitochondrial Ca2+ stores in an ATP-dependent way and that in a physiological resting state the nonmitochondrial Ca2+ store, probably the endoplasmic reticulum, is the major site for the sequestration. PMID- 2579965 TI - Modification of a new high-performance liquid chromatographic method for bleomycin to separate epi-, iso-, desamido-, and unmodified analogues. PMID- 2579964 TI - Mental ability, symbolic play and receptive and expressive language of young children with Down's syndrome. AB - The relationship between measures of mental ability, symbolic play and expressive and receptive language was investigated in a sample of 73 children with Down's syndrome (mean CA 48.9 months, range 19-90 months; mean MA 30.4 months, range 13 73 months). Language delay became increasingly apparent with age, and more so in boys than girls. There was no significant difference between mental ages derived from standard ability tests and corresponding age equivalent scores of the Lowe and Costello symbolic play test. A developmental progression of play similar to that seen in non-handicapped groups was found. However, it is suggested that the use of a more detailed scoring system would be informative. PMID- 2579966 TI - Gel permeation chromatography with interference refractometry for the rapid assay of polydisperse dextrans in biological fluids. AB - A semi-automatic system incorporating an ultra-sensitive interference refractometer coupled to a dual-column gel permeation apparatus has been devised for measurement of the molecular size distribution of dextrans in small samples of serum and urine. The system was calibrated with seventeen defined dextran fractions with a range of 1200-250,000 weight average molecular weight (Mw). Urine samples were prepared for analysis by passage through small ion-exchange columns; serum was pretreated by precipitation with trichloroacetic acid and centrifuged before the ion-exchange treatment. Internal standard (dextran, 2 X 10(6) Mw) was added to each sample before pretreatment. Data were obtained in a form suitable for computerised analysis. PMID- 2579967 TI - Management of hyperthyroidism in children and adolescents. AB - Between 1961 and 1984, 262 patients with hyperthyroidism due to Graves' disease between the ages of 3 and 18 yr were treated in the author's clinic. This paper compares the results of different treatment methods. Initial treatment was surgery for 7 patients, radioiodine for 73, and an antithyroid drug for 182. Seven drug-treated patients subsequently had surgery. Of 14 surgically treated patients, 5 relapsed and received radioiodine, 5 became hypothyroid, 3 were lost to follow-up, and 1 remained euthyroid. Sixteen drug-treated patients were lost to follow-up; 7 are still taking drugs. Of the remaining 99 drug-treated patients not achieving remission, 92 received radioiodine, and 7 had surgery (1 later relapsed and received radioiodine). The principal reasons for abandoning drugs were toxicity, noncompliance, poor control, and failure to achieve sustained remissions. Of 61 drug-treated patients who achieved remission, 22 relapsed (21 were treated with radioiodine and 1 with drug). Remissions after antithyroid drug therapy persist in 39 patients, 2 of whom are now hypothyroid and 10 of whom have been in remission less than 2 yr. Of the 239 subjects whose treatment is complete, 191 (80%) ultimately had radioiodine. One radioiodine treatment eliminated hyperthyroidism in 163 patients, 2 treatments were effective in 17, and 3 treatments were effective in 1. The remaining 5 patients were lost to follow-up after radioiodine before the outcome of therapy could be determined. No increase in congenital abnormalities was found in 63 children of these patients, regardless of treatment. Radioiodine is a safe, simple, and economical therapy for patients with hyperthyroidism and is now considered the initial treatment of choice for such patients. PMID- 2579968 TI - Interaction of furosemide with serum thyroxine-binding sites: in vivo and in vitro studies and comparison with other inhibitors. AB - The diuretic furosemide inhibits serum protein binding of T4 in equilibrium dialysis, dextran-charcoal, and competitive ligand binding separation systems and displaces [125I]T4 from isolated preparations of T4-binding globulin (TBG), prealbumin, and albumin. Equilibrium dialysis studies of undiluted normal serum showed that about 10 micrograms/ml furosemide increased the free T4 and free T3 fractions. Displacement occurred at lower drug concentrations in sera with subnormal albumin and TBG levels. Binding of [14C]furosemide to TBG was inhibited by unlabeled T4, suggesting that furosemide and T4 share a common binding site. A single oral dose of 500 mg furosemide given to five patients maintained on peritoneal dialysis increased the percentage of charcoal uptake of [125I]T4 (using serum diluted 1:10) from 4.1 +/- 1.0 (+/- SE) to 10.8 +/- 4.3 (P less than 0.01) after 2 h, while decreasing total T3 from 75 +/- 5 to 56 +/- 13 ng/dl (P less than 0.01) and total T4 from 6.7 +/- 0.9 to 4.8 +/- 0.8 micrograms/dl (P less than 0.01) after 5 h. Various ligands inhibited [125I]T4 binding to serum proteins in the following relative molar relationship: T4, 1; furosemide, 1.5 X 10(3); fenclofenac, 2 X 10(4); mefenamic acid. 2.5 X 10(4); diphenylhydantoin, 4 X 10[4); ethacrynic acid, 10(5); heparin 5 X 10(5); 2-hydroxybenzoylglycine, 10(6); and sodium salicylate, 1.5 X 10(6). These studies demonstrate that furosemide competes for T4-binding sites on TBG, prealbumin, and albumin, so that a single high dose can acutely lower total T4 and T3 levels. The drug is much more potent on a molar basis than other drug inhibitors of T4 binding, but at normal therapeutic concentrations, furosemide is unlikely to decrease serum T4 or T3. However, high doses, diminished renal clearance, hypoalbuminemia, and low TBG accentuate its T4- and T3-lowering effect. Hence, furosemide should be considered a possible cause of low thyroid hormone levels in patients with critical illness. The significance of this drug in reports of impaired hormone and drug binding in renal failure requires further assessment. PMID- 2579971 TI - Neuropsychological analysis of a case of reduplicative paramnesia. AB - Following a right cerebral hemispheric CVA, a patient showed extensive reduplication of place (his hospital) and occasional reduplication of person. His language was essentially intact, but he was deficient on tests of conceptualization and on nonverbal tasks, both visual and auditory. Short- and long-term memory for nonverbal but not verbal material were also impaired. However, he had sufficient "memory" for the reduplicated hospitals to comment that they were spatially identical. He simply seemed unable to treat these memories as representing the same phenomena. Neuropsychological analysis suggest that reduplicative paramnesia represents a combination of perceptual and memory deficits as well as impaired ability to integrate information. PMID- 2579969 TI - Ion channels in lymphocytes. AB - The advent of the gigaohm-seal recording technique has enabled the study of the electrical properties of small cells, such as individual lymphocytes. Recent studies using this technique in combination with standard immunological and biochemical techniques indicate that cells of the immune system may utilize ion channels, similar in properties to those described in nerve and muscle, in the process of activation. For example, potassium channels may be required for T lymphocyte mitogenesis and calcium channels for antibody production. This article summarizes these recent reports. PMID- 2579970 TI - Immune function in chronic active Epstein-Barr virus infection. AB - The spectrum of illness attributed to Epstein-Barr virus (EBV) includes patients with symptoms persisting for more than 1 year without any other obvious underlying disease. High titers of antibodies to EBV, either IgG antiviral capsid antigen or anti-early antigen, can be demonstrated. In this study, 13 patients diagnosed as having chronic active EBV infection were examined to determine aspects of their immunologic status. Morphological examination and fluorescent antibody analysis revealed no abnormalities in the phenotypes of peripheral blood white cells present in these patients. Compared to those from healthy control individuals, mononuclear cells from the patients showed a markedly depressed ability to produce both interleukin-2 and interferon after stimulation with mitogen and a phorbol ester. Studies of natural killer (NK) cell activity revealed that unfractionated mononuclear cells from patients with chronic active EBV infection were significantly lower in killing activity compared to the control group. Fractionation procedures to enrich for large granular lymphocytes resulted in an increase in NK activity for all individuals, but killing activity still remained slightly lower in the patients than in the control group. The dysfunctions which were found in patients with chronic active EBV infection may reflect a primary defect in natural immune functions of the patients predisposing them to a chronic or intermittent clinical disease rather than a self-limiting illness. Alternatively, the abnormalities detected in these experiments may be a result of the viral infection itself. PMID- 2579972 TI - Comparison of the Scott Selecticult-HSV kit with conventional culture and direct immunoperoxidase staining for detection of herpes simplex virus in cultures of clinical specimens. AB - In a comparative study, clinical specimens were cultured for herpes simplex virus (HSV). The presence of virus was noted by the appearance of characteristic cytopathic effect, as determined by standard direct immunofluorescence techniques, by using a direct immunoperoxidase stain for viral antigen, or by using the Selecticult-HSV (SC-HSV) stain for viral antigen. There was 100% correlation between the SC-HSV stain and immunofluorescence staining in recognizing HSV-infected cells (81 of 81 positive specimens). In comparison with observation of cytopathic effect, the SC-HSV system and conventional culture detected 93 and 78% of positive cultures at 48 h postinoculation and 76 and 32%, respectively, at 24 h. By 5 days postinoculation, SC-HSV detected 100% of the positive specimens. As compared with the direct immunoperoxidase stain, SC-HSV stain was slightly more sensitive and gave less background stain. HSV serotypes 1 and 2 were both detected by the SC-HSV stain. The Scott SC-HSV kit appears to be an effective system for the diagnosis of HSV infections. PMID- 2579974 TI - Slipped capital femoral epiphysis: a pathological study. II. An ultrastructural study of 23 cases. AB - Twenty-three core biopsy specimens from patients with slipped capital femoral epiphysis and 11 control growth plates were studied by electron microscopy. Block staining with toluidine blue for demonstration of proteoglycans at the ultrastructural level was also used. The proliferative and hypertrophic zones of slipped growth plates showed diminished cellularity and marked distortion of the architecture with disarray of the cartilage columns. There was a deficiency and abnormality in the supporting collagenous framework of slipped plates. Chondrocyte degeneration and death were seen at all levels of the proliferative and hypertrophic zones, suggesting a disturbance in the life cycle of chondrocytes. The significance of these findings and their relationship to mechanistic, endocrine, and other proposed etiologies of epiphyseal slipping is discussed. PMID- 2579973 TI - Slipped capital femoral epiphysis: a pathological study. I. A light microscopic and histochemical study of 21 cases. AB - Core biopsy specimens of slipped proximal femoral epiphyseal growth plates and of normal controls were examined by light microscopy and histochemistry. Slipped growth plates showed diminished cellularity with an overall excess of matrix as well as severe disorientation and misalignment of chondrocytes. Decrease in number of argyrophilic fibers in the longitudinal septa suggested deficiency in collagen. Histochemical staining of slipped plates did not deviate from normal except in severely deformed areas. Anatomic and histochemical observations did not conclusively support or exclude biochemical or biomechanical factors in the etiology of epiphyseal slipping. PMID- 2579975 TI - Formation of methotrexate polyglutamates in purified myeloid precursor cells from normal human bone marrow. AB - Immature myeloid precursor cells were preferentially selected from normal human bone marrow by using immune rosette techniques that employed monoclonal antibodies against mature granulocytes, monocytes, T and B lymphocytes, and erythroid precursors (Mo5, M3, OKT3, B1, and EP1, respectively). We examined the formation, retention, and cytotoxic effects of methotrexate (MTX) polyglutamates (MTX-PGs) in these purified myeloid precursor cells. After 1- and 24-h exposures to MTX, with thymidine and deoxyinosine as rescue, the intracellular MTX-PG profile was examined by high-pressure liquid chromatography. Efflux patterns of MTX-PGs were also studied after additional 1- and 24-h incubations in drug-free media. Cytotoxic effects of retained MTX-PGs on bone marrow myeloid precursors were examined by colony formation in drug-free semisolid agar. Normal myeloid precursor cells converted MTX to MTX-PGs in a concentration- and time-dependent manner, preferentially retaining MTX-PGs with three to five glutamyl moieties. At low concentrations of MTX (1 microM), MTX-PG formation was insufficient to maintain saturation of the target enzyme dihydrofolate reductase after removal of drug from the incubation medium, and there was no decrease in myeloid colony formation. At higher concentrations of MTX (10 microM), formation of higher molecular weight polyglutamates was sufficient to allow for 24-h saturation of intracellular binding capacity after removal of extracellular drug and resulted in a 35% reduction in the formation of colony-forming units in culture. Comparison of MTX metabolism in normal bone marrow cells and the MTX-sensitive HL 60 human leukemia cell line showed twofold greater PG formation by these tumor cells after 24-h exposure to 1 or 10 microM MTX, and a marked (greater than 30 fold) increase in cytotoxicity for the HL-60 cells as compared with normal myeloid precursors, suggesting that the MTX polyglutamation may be important to its selective antitumor action. PMID- 2579976 TI - A soluble suppressor T cell factor protects against experimental intraabdominal abscesses. AB - This paper describes a suppressor T cell factor which protects mice against intraabdominal abscesses caused by Bacteroides fragilis. This soluble cell-free factor (ITF) is derived from splenic T cells from mice immunized with capsular polysaccharide (CP) of B. fragilis. Mice receiving ITF are protected from developing abscesses caused by B. fragilis to the same degree as animals receiving intact immune splenic T cells. The factor appears to be small in molecular size as protective activity is dialyzable through a 12,000-mol wt exclusion dialysis membrane and is present in fractions intermediate between the bed and void volumes of a P2 Biogel column. The protective effect of ITF is antigen-specific to B. fragilis alone. Mice given a complex inoculum of B. fragilis, enterococcus, and another anaerobe develop abscesses even after receiving column-purified ITF. The activity of ITF also is eliminated after adsorption with B. fragilis CP coupled to sheep erythrocytes but not with an unrelated CP coupled to sheep erythrocytes. ITF, therefore, appears to have a binding site for B. fragilis CP. ITF is heat-labile and loses efficacy after protease digestion, suggesting that the active material is a protein. These studies define a suppressor cell factor with activity in a model system resembling human disease and offer promise for increased understanding of the diversity of cell-mediated immune systems. PMID- 2579978 TI - Ontogenesis of taurocholate transport by rat ileal brush border membrane vesicles. AB - Developmental aspects of taurocholate transport into ileal brush border membrane vesicles were studied in 2-wk-old (suckling), 3-wk-old (weanling), and 6-wk-old (adolescent) rats. Taurocholate uptake (picomoles per milligram protein) into brush border membrane vesicles prepared from 2-wk-old rats was similar under Na+ and K+ gradient conditions (outside greater than inside). By contrast, uptake in 3- and 6-wk-old rats was significantly enhanced at 20 s, and at 1, 2, and 5 min of incubation in the presence of a Na+ gradient when compared with a K+ gradient incubation (P less than 0.05). Under isotope exchange conditions, a plot of active uptake velocity versus taurocholate concentration (0.10-1.0 mM) in 2-wk old rat membrane vesicles was linear and approached the horizontal axis, suggesting the absence of active transport. However, similar plots in 3- and 6-wk old rats described a rectangular hyperbola, indicating a Na+-dependent, saturable cotransport system. Woolf-Augustinsson-Hofstee plots of the uptake velocity versus concentration data from 3- and 6-wk-old rat brush border membrane vesicles yielded Vmax values that were not significantly different, 844 and 884 pmol uptake/mg protein per 120 s, respectively. The respective Km values were 0.59 and 0.66 mM taurocholate. The induction of an electrochemical diffusion potential by incubating K+-loaded vesicles with valinomycin did not significantly enhance taurocholate uptake in 2-, 3-, or 6-wk-old rat vesicle preparations. These data indicate that taurocholate transport into rat ileal brush border membrane vesicles is mediated by an electroneutral, sodium-coupled, cotransport system that is incompletely developed in the 2-wk-old suckling rat but fully developed by the time of weaning at 3 wk of age. PMID- 2579977 TI - Maintenance of antigen specificity by human interleukin-2-dependent T cell lines. Use of antigen-presenting cells and OKT3 antibody in the absence of antigen. AB - The in vitro growth of T cells obtained from localized anatomic sites of pathology may offer a new approach to the investigation of certain human autoimmune diseases. However, if interleukin-2-dependent T cell cloning is to be useful in helping to elucidate putative pathogenetic antigens in these diseases, the expansion of the small number of T cells obtainable from localized anatomic sites of pathology will often have to be accomplished in the absence of these, as yet undetermined, antigens. At present, it is a generally held belief that antigen-responsive, interleukin-2-dependent T cell lines and clones will lose antigen responsiveness if propagated in the absence of specific antigen. Thus, the use of T cell cloning might be viewed as being of limited usefulness in the investigation of certain human autoimmune diseases. In this report we demonstrate that, when propagated in the absence of antigen, human tetanus toxoid-specific, interleukin-2-dependent T cell lines will indeed lose antigen reactivity. However, if propagated in the absence of antigen but in the presence of antigen presenting cells, the tetanus toxoid reactivity of a subset of such lines can be maintained. Moreover, the propagation with OKT3 antibody, in addition to antigen presenting cells, may be even more effective in maintaining antigen reactivity. These results may suggest a new approach to the use of T cell cloning technology in the investigation of certain autoimmune diseases. PMID- 2579979 TI - Suprapubic sonographic detection of prostate carcinoma. AB - Between January 1 and March 31, 1983, 103 patients scheduled for prostatic surgery were blindly evaluated preoperatively by suprapubic real time sonography. Prospectively, the sensitivity was 72.7%, specificity 72.2%, predictive value of positive test 51.6% and predictive value of negative 86.7% for the detection of prostatic carcinoma. Retrospective analysis increased the sensitivity to 86% and when clinical information was utilized, only one carcinoma escaped detection. Unfortunately, both prostatic inflammation and occasionally benign prostatic hypertrophy may simulate carcinoma sonographically, thus producing a significant number of false positives. No ultrasonically detectable characteristics could be found which unequivocally separate carcinomas from inflammation and hypertrophy. For this reason routine suprapubic screening does not seem warranted. PMID- 2579980 TI - Immunohistochemical demonstration of differential substance P-, met-enkephalin-, and glutamic-acid-decarboxylase-containing cell body and axon distributions in the corpus striatum of the cat. AB - The immunohistochemical localization of neuronal cell bodies and axons reactive for substance P (SP) and methionine-enkephalin (ME) was investigated in the corpus striatum of the adult cat brain and compared with that of glutamate decarboxylase (GAD), synthetic enzyme for gamma-aminobutyric acid. Striatal cell bodies reactive for ME could be identified only in colchicine treated cats, are medium size, ovoid striatal cells, and are found in large numbers in a more or less even distribution throughout the caudate nucleus, putamen, and nucleus accumbens. The striatal region most densely occupied by ME-immunoreactive cells is the ventral and central part of the caudate head. Modest numbers of larger ME reactive neurons are dispersed throughout the entopeduncular nucleus and the pars reticulata of the substantia nigra. Striatal cells of medium size reactive for SP could be identified, with or without colchicine, in largest numbers in the medial half of the caudal three-fourths of the putamen and in clusters of irregular size and shape in the head of the caudate nucleus. Cells reactive for SP are also common in layer II and the islands of Calleja of the olfactory tubercle. We could not reliably visualize GAD-positive cell bodies in the striatum, even with colchicine treatment; however, they could be seen readily in all pallidal structures such as the globus pallidus, ventral pallidum, entopeduncular nucleus, and substantia nigra. Axons reactive for ME are found mainly in the globus pallidus where they form a dense and even network throughout the nucleus. The globus pallidus is almost devoid of SP reactivity except near its extreme caudal pole. Conversely, SP-immunoreactive axons form dense meshworks in the entopeduncular nucleus and substantia nigra where ME immunoreactivity is minimal. Fewer, but still ample numbers, of SP-reactive axons are present also in the ventral tegmental and retrorubral areas of the midbrain tegmentum and in the ventral pallidum of the basal forebrain, but only sparse ME-reactive axons are present in these areas. This differential distribution of SP- and ME-containing axons in the pallidal and nigral structures stands in contrast to the relatively homogeneous and dense distribution of GAD-containing axons throughout the dorsal and ventral pallidum, entopeduncular nucleus, and substantia nigra.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2579981 TI - Cobalt injected into the right and left fasciculi retroflexes clarifies the organization of this pathway. AB - A cobaltic lysine complex was injected separately into the right and left fasciculi retroflexes of the frog. This tracing technique labeled, in a Golgi like manner, the neurons which initiate the fasciculi retroflexes and revealed details of their morphological pattern. The fasciculi retroflexes originate from various neurons distributed in the diencephalon and mesencephalon, but their main source is the habenular nuclei. In the frog there are dorsal and ventral habenulae which are homologous to the medial and lateral habenulae, respectively, of mammals. In the frog the dorsal habenulae are strikingly asymmetric. Our study shows that the fasciculus retroflexus is composed of several compact separated bundles of fibers and that the fibers originating from the dorsal habenular nuclei project to the interpeduncular nucleus, while those originating from the ventral habenular nuclei project beyond the interpeduncular nucleus, but so far we have not been able to show the exact site of their termination. The labeling of cells within the interpeduncular nucleus raises the possibility that the habenulo-interpeduncular tract is reciprocal in function. The finds support our previously reported hypothesis on the theoretical interpretation of the functional circuitry of the frog habenulo-interpeduncular system. PMID- 2579982 TI - The ultrastructural localization of enkephalin and substance P immunoreactivities in the nucleus tractus solitarii of the cat. AB - In the medial and commissural subdivisions of the nucleus tractus solitarii enkephalin and substance P immunoreactivities were localized within synaptic terminals, unmyelinated axons, and neuronal cell bodies. Both enkephalin and substance P immunoreactivities were contained within synaptic terminals which had a mixture of small clear vesicles and dense core vesicles. The presence of dense core vesicles within both the enkephalin- and substance P-immunoreactive terminals was a consistent feature, although they were not associated with the actual synaptic junction. While enkephalin- and substance P-immunoreactive terminals shared a similar morphology, their respective distributions along the dendritic tree were quite distinct. Enkephalin-immunoreactive terminals contacted mainly the cell body and proximal portions of the dendritic tree. In contrast, substance P-immunoreactive terminals synapsed predominantly with spines and shafts of small to medium-sized dendrites. Few substance P-immunoreactive terminals contacted proximal dendrites and they were never presynaptic to the neuronal cell body. This apparent segregation of synaptic terminals on neurons suggests that enkephalin synapses have a more pronounced effect than substance P terminals. PMID- 2579983 TI - Distribution and origin of calcitonin gene-related peptide (CGRP) immunoreactivity in the sensory innervation of the mammalian eye. AB - The occurrence, distribution, and origin of immunoreactive calcitonin gene related peptide (CGRP) in nerves of rat, guinea pig, cat, and monkey eyes were investigated by immunocytochemistry, radioimmunoassay, and chromatography. A rich network of CGRP-immunoreactive nerve fibres was noted in the anterior uvea, which was widely distributed in both dilator and constrictor pupillae muscles and extended to the ciliary body and uveal blood vessels. Numerous CGRP immunoreactive neuronal cells were present in the trigeminal ganglion. The extractable CGRP was 8.6 +/- 1.8 pmoles/gm of tissue in the iris and 44.0 +/- 8.1 pmoles/gm in the trigeminal ganglion. Following damage to the Gasserian ganglion a marked decrease of CGRP immunoreactivity was observed in the anterior uvea (control 11.3 +/- 1.6 pmoles/gm; operated 1.4 +/- 0.1 pmoles/gm) confirming the origin of the immunoreactive fibres from trigeminal primary sensory neurons. The sensory nature of the CGRP-immunoreactive fibres was substantiated by the depletion of CGRP immunoreactivity observed after treatment with capsaicin, which is known to cause selective degeneration of sensory neurons. Comparative studies on the distribution and colocalisation of CGRP and the putative sensory neurotransmitter substance P revealed a closely parallel distribution of the two peptides in certain regions of the uvea and their coexistence in a subpopulation of trigeminal primary sensory neurons. This study suggests that the sensory nervous system in the eye is more heterogeneous in terms of its putative neurotransmitters than previously indicated. PMID- 2579984 TI - The structure of the nucleus of the lateral olfactory tract. AB - The nucleus of the lateral olfactory tract (NLOT) was studied in rats with the rapid Golgi method. The nucleus is in the rostral part of the amygdala and has three distinct layers. Layer I is a superficial, fibrous layer; layer II, an intermediate, cell-dense layer; and layer III, a loosely textured cell and fiber layer. The commissural component of the stria terminalis forms at the apex of layer III. Layer II contains pyramidal and stellate cells; the former is more abundant. The apical dendrites of the pyramidal cells bow outward, point ventrally, and extend through layer I to the pial surface. The apical and basilar dendrites weave a dendrite capsule around layer II, except along its border with layer I. Most pyramidal cell axons go dorsally through layer III into the commissural component of the stria terminalis. The axons normally give off long, thin collaterals that travel rostrally into the forebrain. Other, shorter collaterals remain near the parent cell. Stellate cells have spine-poor dendrites that radiate throughout layers I and II. Their axons generate a dense terminal field that is confined to layer II. A special group of neurons, the border neurons, occur along the junction between layers I and II. Many of them look like modified pyramidal cells, and some look like horizontal cells. The axons of the latter ramify among the pyramidal cell apical bouquet dendrites in layer I. Along the perimeter of layer I, near the pial surface, are rounded cell bodies that have moderately spiny dendrites and axons that project dorsally. Layer III neurons are the largest cells in the NLOT. Three types of large cells were identified: large spiny neurons, large nonspiny neurons, and pyramidal cells, which were least common. The dendrites of all three neuron types reach beyond layer III into layer II or the adjacent anterior amygdala. Their axons were not followed far. They travel dorsally and give off a few collaterals, some of which enter layer II. Also in layer III, mainly in its apical region, are small nonspiny cells. Their dendrites and axons appear to be limited to layer III. The afferent fibers in layer I generally run parallel to the pial surface. They have a few short collaterals and boutons en passant. One afferent group in layer I is made up of thick axons that enter via the rostral edge of the layer.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2579985 TI - The distribution of bovine pancreatic polypeptide/FMRFamide-like immunoreactivity in the ventral nervous system of the locust. AB - The distribution of bovine pancreatic polypeptide (BPP) FMRFamide-like immunoreactivity is described in the ganglia of the ventral nerve cord and in the peripheral median nervous system of the locust, Schistocerca gregaria. Immunoreactive cell bodies occur in three regions of the thoracic ganglia: 1) two pairs of cells lie in the anterior of the ganglion ventral to the root of nerve 1 and the anterior ventral association centre; 2) a group of cells lies in the ventral midline at the level at which nerves 3 and 4 leave the ganglion; 3) and two bilaterally symmetrical, posterior lateral groups lie between nerves 5 and 6 at the edge of the ganglion. Immunoreactive cell bodies in the suboesophageal and abdominal ganglia are confined to the midline and are distributed along the anterior-posterior axis both dorsally and ventrally. The processes of the posterior lateral groups have been traced into the neurohaemal organs of the median nerve and beyond. In the periphery such processes innervate the salivary glands and various muscles. The nature of the endogenous antigen contained in the immunoreactive cells has been investigated with the use of antisera against other peptides of the pancreatic polypeptide family, namely avian pancreatic polypeptide, neuropeptide Y, and peptide YY. In addition, BPP antisera not specific for the C terminal hexapeptide have been tested. Liquid preabsorption experiments with BPP and FMRFamide (the molluscan cardioacceleratory peptide) suggest that the endogenous peptide antigen contained in the stained neurones may belong to the pancreatic polypeptide family or to the FMRFamide family. PMID- 2579987 TI - Monoclonal antibodies and cutaneous T cell lymphoma. Theoretical and practical considerations. AB - The T cell nature of mycosis fungoides and Sezary syndrome was established a decade ago. The recent advent of monoclonal antibodies to T cells and other lymphoid subpopulations has resulted in an explosion of knowledge on the biology of this group of disorders. These reagents have increased our knowledge on thymic differentiation status, pathogenesis, the phenotype of premalignant vs malignant lymphocytic infiltrates, the identification of other previously unrecognized cells within lymphomas, and the phenotype of circulating vs skin lymphocytes. Therapeutic applications may result. These new developments are discussed. PMID- 2579986 TI - The distribution of substance P, enkephalin, and serotonin immunoreactivities in the area postrema of the rat and cat. AB - With the use of the peroxidase-antiperoxidase technique the distribution of substance P (SP), enkephalin (ENK), and serotonin (5HT) immunoreactivities were described in the area postrema of the rat and cat. In both species, immunoreactivity in the area postrema was differentially distributed as either fibers only, or cell bodies and fibers. In the rat and cat, ENK had the greatest accumulation of immunoreactive fibers, followed by 5HT and SP. In the area postrema of the rat the majority of SP-, ENK-, and 5HT-immunoreactive fibers were along the ventral and ventrolateral borders, with fewer immunostained fibers at the dorsal surface. The area postrema of the cat had the majority of SP-, ENK-, and 5HT-immunoreactive fibers at the ventral and lateral borders, with fewer immunostained fibers at the dorsal and medial borders. In both species, the area postrema's central region contained the fewest immunostained fibers. In general, for each putative neurotransmitter examined, immunostained fibers in both species progressively decreased in number rostrocaudally. Serotonin- and ENK immunoreactive cell bodies were found in the rat area postrema; in the cat area postrema only ENK-immunoreactive cell bodies were present. The area postrema of both species lacked SP-immunoreactive cell bodies. The heterogeneous distribution of immunoreactive fibers and cell bodies within the area postrema of the rat and cat may reflect the different functions of the area postrema in both species. PMID- 2579988 TI - Clinical and immunologic response to Isoprinosine in alopecia areata and alopecia universalis: association with autoantibodies. AB - Twenty patients with alopecia universalis, alopecia semiuniversalis and alopecia areata were studied for their immune parameters. Fourteen of them received an oral treatment with Isoprinosine, a synthetic immunomodulator. Ten patients showed the presence of several autoantibodies. No significant abnormalities in various T cell rosette markers were found, but T4/T8 ratios tended to be elevated. Erythrocyte antibody complement (EAC) rosettes were usually decreased. Treatment with Isoprinosine produced a clinical response, as judged by total or partial hair growth, in nine of the fourteen patients treated. It was striking to observe that seven of the nine responders had autoantibodies prior to treatment. These autoantibodies disappeared or decreased with Isoprinosine therapy. In contrast, only one of five nonresponders had serum autoantibodies. After treatment, both groups showed an increase in blood-active T rosettes. These results suggest that alopecia is a heterogeneous disease subdivided by the presence or absence of autoantibodies since clinical response was mainly obtained in patients presenting autoantibodies. PMID- 2579989 TI - Ultrastructural localization of cAMP-dependent protein kinase subunits in regenerating rat hepatocytes using immunogold electron microscopy. AB - We have used the indirect colloidal immunogold technique to examine the ultrastructural localization and distribution of the regulatory subunits (RI and RII) and catalytic subunit (C) of cAMP-dependent protein kinase (cA-PK) in hepatocyte nuclei during the prereplicative phase of rat liver regeneration. The technique allowed the localization of all three subunits of cA-PK in hepatocyte nuclei. Morphometric quantitation of the relative staining intensity of nuclear antigen indicated a marked increase of immunogold staining of nuclear RI and C 16 hours following partial hepatectomy. In contrast, staining of nuclear RII was not affected. These immunocytochemical observations correlate well with our previous data (Laks, M.S. et al. (1981) J. Biol. Chem. 256, 8775-8785) obtained by biochemical methods indicating a modulation of cA-PK activity after partial hepatectomy. PMID- 2579990 TI - Enterotoxigenic Escherichia coli infections in newborn calves: a review. AB - Diarrhea caused by enterotoxigenic Escherichia coli is an infectious bacterial disease of calves that occurs during the first few days of life. The Escherichia coli that cause the disease possess special attributes of virulence that allow them to colonize the small intestine and produce an enterotoxin that causes hypersecretion of fluid into the intestinal lumen. These enterotoxigenic Escherichia coli are shed into the environment by infected animals in the herd and are ingested by newborn calves soon after birth. There is some natural immunity to enterotoxigenic Escherichia coli; however, it often fails to protect calves born and raised under modern husbandry conditions. Hence, methods have been developed to stimulate protective immunity by vaccination of the dam. The protective antibodies are transferred passively to calves through the colostrum. PMID- 2579991 TI - African "eosinophilic bodies" in vivo in two American men with Kaposi's sarcoma and AIDS. AB - Pink-stained (hematoxylin and eosin), variably sized, round-shaped, intracellular and extracellular "eosinophilic bodies," commonly observed in African cases of Kaposi's sarcoma (KS), were discovered in cutaneous KS tumors of two American men with AIDS (the acquired immune deficiency syndrome). These "bodies" were also identified in Gram-, Giemsa-, and Fite-stained (acid-fast) sections. The exact nature of eosinophilic bodies is unknown, but they are thought to be related to Russell bodies. Further study of eosinophilic bodies in KS may shed light on the pathogenesis of these tumors, as they occur in the epidemic of AIDS. PMID- 2579992 TI - [Characteristics of the transcription activity of liver nuclear DNA in long-term adaptation to altitude hypoxia]. PMID- 2579993 TI - [Mechanism of microwave action on model membrane systems]. PMID- 2579995 TI - Pancreatitis: is total serum amylase misleading? PMID- 2579996 TI - Immunocytochemical studies of relaxin in ovaries of pregnant and cycling mice. AB - Immunocytochemical staining for relaxin in ovarian sections of pregnant mice from day 11 through day 18 of gestation revealed that only corpora lutea (CL) of pregnancy are stained. Evaluation of serial sections of ovaries from a day 16 pregnant mouse revealed that the only luteal structures present are CL of pregnancy. The number of CL present in each ovary equaled the number of implantation sites in each related horn (7 on the right side and 8 on the left side). These large CL varied in shape, being round in some profiles to very elongate in others. All CL were immunochemically stained for relaxin using the peroxidase-antiperoxidase method of L. Sternberger (Immunocytochemistry, 2nd ed. Wiley, New York, 1979). The intensity of the strain varied from cell to cell within each CL. Small luteal structures that were observed to be immunochemically stained for relaxin were demonstrated to represent the periphery of CL of pregnancy. No luteinized follicles were observed and interstitial cells and follicles were not immunochemically stained in any of the day 16 serial ovarian sections or in any of the ovarian sections from pregnant mice on the other days of gestation studied. CL of previous cycles were not observed to be present in the ovaries at days 15, 16, or 18 of gestation. However on day 14 and before, CL of previous cycles were observed and they did not exhibit any relaxin immunostaining. Immunocytochemical studies using the biotin-avidin system revealed that no relaxin immunostaining could be demonstrated in the ovaries of cycling mice at any stage of the estrous cycle. In conclusion, this study revealed that the only ovarian structures demonstrating relaxin immunocytochemical staining in the mouse were CL of pregnancy. PMID- 2579994 TI - Recent developments in immunomodulatory therapy. PMID- 2579997 TI - Immunohistochemical demonstration and localization of Lewis a and Lewis b determinants in human urothelium. AB - In order to obtain baseline information about Lewis antigen expression in human urothelium in order that changes during malignant transformation can be evaluated, urothelium from eight individuals of known erythrocyte Lewis types were stained by a Tween-modified indirect immunoperoxidase staining technique using goat antibodies directed toward the Lewis a and Lewis b determinants and mouse monoclonal antibodies directed toward the Lewis a determinant in serial dilutions. To evaluate the value of the method for tissue Lewis typing, eleven ureters from individuals of unknown erythrocyte Lewis types were stained using goat antibodies. The Lewis antigens were located on the cell membranes and in the cytoplasm of urothelial cells. Goat antibodies identified Lea-b-, Lea+b+, and Lea+b- urothelium. Monoclonal antibodies identified urothelium with both low and high Lewis a antigen expression as well as urothelium with no Lewis a antigen expression. Urothelial Lewis antigen expression correlated with erythrocyte Lewis types in Lea-b+ and Lea+b- individuals. In Lea-b- individuals Lewis determinants were either not detected or were expressed similarly to Lea-b+ individuals. Urothelial Lewis typing were doubtful in two out of the eleven ureters examined. The results imply that knowledge about erythrocyte Lewis type or normal tissue Lewis antigen expression is necessary for the immunohistochemical evaluation of changes in Lewis antigen expression in urothelial tumors. PMID- 2579998 TI - Multiple binding modes for Hoechst 33258 to DNA. AB - Two binding modes for the bisbenzimidazole Hoechst 33258 to native DNA at physiological conditions have been distinguished. Type 1 binding, which dominated at low dye/phosphate ratios (D/P less than 0.05) or low dye concentrations, had a high quantum yield of fluorescence with maximum emission at 460 nm. Binding of the dye at type 2 sites (0.05 less than D/P less than 0.4) lead to quenching of fluorescence from type 1 bound dye, presumably by nonradiative energy transfer. Fluorescence quantum yield of type 2 bound dye was low (phi = 0.05-0.1) and it peaked around 490 nm. At D/P greater than 0.4, the dye/DNA complex precipitated. This was caused by an additional dye-DNA interaction that was strongly cooperative. The anomalous dispersion of the refractive index of the complex changed abruptly around D/P = 0.4, indicating that the precipitating dye-DNA interaction involved strong electronic interaction between dye molecules. Hoechst 33258 precipitated polynucleotides irrespective of strandedness and base composition when dye concentration was raised above 1 X 10(-5) M. In the presence of 25% ethanol, type 2 binding to DNA did not occur, whereas the binding constant for type 1 binding (kappa = 2 X 10(3) M-1) was about two orders of magnitude smaller than in physiological buffer. DNA was not precipitated by high concentrations of Hoechst 33258 in 25% ethanol. PMID- 2579999 TI - Evaluation of techniques for immunofluorescent staining of microtubules in cultured plant cells. AB - Various modifications to the immunofluorescent labeling procedures for microtubules in plant cells have been compared using cell cultures of Vicia hajastana Grossh. Using serial section electron microscopic reconstructions as a reference, we have chosen as our standard procedure a method that maximizes both the preservation of the cytoskeleton and the proportion of cells staining, while minimizing the degree of nonspecific staining. The critical steps of the procedure include stabilization of the cytoskeleton, cell wall permeabilization, and cell extraction. To maintain structural integrity during the procedure, it is necessary to stabilize the cytoskeleton with paraformaldehyde. To facilitate antibody penetration into the cell, it was necessary that the walls be made permeable via partial enzymatic digestion. Detergent extraction of cells increased the proportion of cells staining and decreased the level of nonspecific binding of the antibodies. The procedures detailed in this article provide a good starting point for the application of immunofluorescent labeling techniques to other plant systems. PMID- 2580000 TI - Immunoregulation in the rat: ontogeny of B cell responses to types 1, 2, and T dependent antigens. AB - The development of rat B cells has been examined in neonatal and adult Fischer rats through the use of type 1 (TNP-Brucella abortus), type 2 (TNP-LPS(Ph), TNP Ficoll) and T cell-dependent (TD) (SRBC) antigens. In vivo splenic PFC responses to TNP-Brucella abortus could be induced in newborn rats and by 12 days of age had reached adult levels. In contrast, the responses to the type 2 and TD antigens were 30% and 70%, respectively, of the adult levels at 30 days of age. Adoptive transfer of the B cells from neonatal and young rats into irradiated adult hosts demonstrated that the kinetics in the development of responses to these antigens (early for type 1, intermediate for TD, and late for type 2) were not due to limiting accessory cell or T cell help in immature rats. In vitro cultures of purified B cells from neonatal and adult rats were responsive to TNP BA and TNP-LPS(Ph) but not to TNP-Ficoll and SRBC. However, the addition of spleen cell-derived Con A supernatant to the B cell cultures resulted in responses to all four antigens, which arose as a function of B cell age, with kinetics that were identical to those observed in vivo. Fluorescent staining of B cells from rats of various ages for cell surface IgM and analysis on the fluorescence-activated cell sorter (FACS) revealed that all splenic B cells from rats 4 days of age expressed a relatively high level of sIgM, and that a subpopulation that expressed a relatively low level of sIgM increased with age until it represented approximately 50% of the adult splenic B cells. Challenging Con A supernatant-supplemented cultures of FACS-prepared low sIgM+ and high sIgM+ cells revealed that B cells responsive to TNP-Ficoll were confined to the ontogenically late-arising low sIgM+ subpopulation but that B cells responsive to TNP-BA, TNP-LPS(Ph), and SRBC were present in both subpopulations. PMID- 2580001 TI - Synthetic Fc peptide-mediated regulation of the immune response. II. Analysis of secreted immunoglobulin classes, accessory cell contribution, and lymphocyte proliferation in p23-stimulated spleen cell cultures. AB - The synthetic peptide p23 representing residues 335 to 357 in the CH3 domain of human IgG1 was able to increase levels of secreted Ig in murine spleen cell cultures. This in vitro response was optimal in the presence of between 10(-4) and 10(-3) micron p23/ml and the levels of secreted Ig reached a maximum on day 4 or day 5 of culture. Supernatants from p23-treated cell cultures generally contained more IgM than IgG and undetectable levels of IgA. Induction of Ig secretion by p23 was macrophage-independent but T cell-dependent and, with respect to the latter case, removal of T cells from spleen cells reduced the levels of both IgM and IgG. Although maintaining the B cell differentiation inducing quality of its progenitor molecule, the Fc gamma fragment, p23 appeared to have lost the ability to induce B cell proliferation. Evidence is presented that a sequence functionally similar to p23 is extant in mouse IgG by showing that murine Fc gamma fragments were also able to induce increases in Ig-secreting cells in murine spleen cell cultures. PMID- 2580002 TI - B cell activation: role of dendritic and T cell factors in the response to thymic independent and -dependent antigens. AB - We described a cloned dendritic cell, clone Den-1, that is a potent accessory cell for some B cell responses. Clone Den-1 produces a novel lymphokine that is distinct from previously described factors produced by T cells. In the present study, we compare the role of nonspecific helper factors produced by Den-1 (Den-1 SN) or the T cell thymoma EL4 (EL4-SN) in promotion of B cell plaque-forming cell (PFC) responses to a variety of antigens. We find that the antigen in culture determines the B cell requirement for dendritic and/or T cell factors. B cell PFC responses to TNP-Brucella abortus (BA) and TNP-lipopolysaccharide (LPS) are greatly increased by EL4-SN but show little, if any, enhancement with Den-1 SN. Responses to TNP-polyacrylamide are reconstituted by either Den-1 SN or EL4-SN, whereas responses to TNP-Ficoll, TNP-dextran and TNP-levan are reconstituted by Den-1 SN and are much less sensitive to factors present in EL4-SN. Responses to SRBC require the presence of both Den-1 SN and EL4-SN. We also show that the time at which Den-1 SN must be provided to the B cell is dependent on the antigen in culture. Our findings are discussed in terms of present classification of antigens based on their ability to stimulate various B cell subpopulations. PMID- 2580003 TI - Accessory cells in immune suppression. II. Evidence for presentation of idiotype specific suppressor factors to B cell targets by I-A+ accessory cells. AB - The functional suppression of two BALB/c myelomas, MOPC315 and MOPC460, by idiotype-specific suppressor T cells is mediated by secreted factors (TsF). Idiotype-specific TsF only functions in the presence of accessory cells (AC) that can be low density splenocytes or cells of BALB/c B lymphoma A20-2J. Such AC are I-A+ but do not have to be histocompatible with the myeloma targets or the source of TsF. A20-2J cells incubated with soluble idiotype and TsF also are capable of suppressing the relevant myeloma target. The effect of TsF-pulsed A20-2J cells is idiotype specific, and these cells do not secrete immunosuppressive mediators. Finally, TsF-pulsed A20-2J cells suppress myeloma targets when the two are cultured on the same side of a cell-impermeable membrane but not when they are separated by the membrane. These results indicate that I-A+ cells are capable of concentrating and/or presenting TsF to suppressible targets, and they demonstrate a novel role for Ia-bearing cells in immune regulation. PMID- 2580005 TI - Phylogeny of lymphocyte heterogeneity: the cellular requirements for in vitro antibody responses of channel catfish leukocytes. AB - Three functionally distinct leukocyte subpopulations were isolated from the peripheral blood of channel catfish. Surface immunoglobulin-positive (sIg+) and sIg- lymphocytes were isolated by an indirect "planning" procedure employing monoclonal antibodies specific for channel catfish Ig. A third population composed of macrophages was isolated by adherence to baby hamster kidney cell microexudate-coated surfaces. Functional features of these three cell types were established by assessing their role(s) in primary in vitro anti-hapten PFC responses to known murine thymus-dependent (TD) and thymus-independent (TI) antigens. The results indicated that anti-hapten PFC responses to a TI antigen required the presence of sIg+ lymphocytes and macrophages. In contrast, all three cell types were required for responses to TD antigens. Furthermore, the results of studies involving the depletion of antigen-reactive lymphocytes demonstrated that both hapten-specific sIg+ cells and carrier-specific sIg- cells were required for anti-hapten responses to TD antigens. These studies provide direct evidence that catfish have separable B cells (sIg+ lymphocytes), T helper cells (sIg- lymphocytes), and accessory cells (macrophages) quite similar to those seen in higher animals. PMID- 2580004 TI - Control of B cell proliferation: inhibition of responses to B cell mitogens induced by plasma cell tumors. AB - A multitude of factors has been described that positively and negatively regulate B cell proliferation. A model system for the study of negative control of B cell function is provided by mice bearing plasmacytomas (PC-mice). In PC-mice, the primary immune response, as measured by development of antibody-forming cells (AFC), is severely suppressed. The present report specifically identifies a block in B cell proliferation as the apparent cause of this reduction in AFC production. Thus, the proliferative response of B cells from the spleens of PC mice (PC-spleens) was significantly impaired when stimulated with four different B cell mitogens (lipopolysaccharide, Salmonella typhimurium mitogen, anti-mu conjugated to Sepharose, and 8-mercaptoguanosine). Nevertheless, the mitogen responsiveness of these B cells was recovered when they were segregated by various methods from macrophages. These data suggest that the proliferative ability of the B cells in PC-spleens is inherently normal. In concordance with this conclusion, it was shown that suppressor cells from PC-spleens can block the proliferation of normal B cells derived from nontumor-bearing mice. This inhibition does not require direct cell contact and is mediated via soluble factors. The relevance of these results to previous studies of PC-induced immunosuppression and to the control of normal B cell proliferation is discussed. PMID- 2580006 TI - Delayed hypersensitivity and immune protection against herpes simplex virus: suppressor T cells that regulate the induction of delayed hypersensitivity effector T cells also regulate the induction of protective T cells. AB - We have been studying delayed hypersensitivity (DH) to herpes simplex virus (HSV) in order to examine the role of this response in host defense against acute and recurrent HSV infections. In previous reports the basic parameters of DH to HSV have been characterized by using a murine ear swelling model, and also the regulation of DH to HSV induced by i.v. injection of the virus. In this paper, we describe a murine protection system and our use of the ability to specifically regulate DH to HSV to examine the correlation between T cells that transfer DH (TDH) and cells that transfer protection from acute HSV infection. Both DH and protection can be transferred with lymph node cells from mice immunized subcutaneously 4 days previously. The effector cell appears to be a T cell, because serum from these donors confers no protection and treatment of immune cells with anti-Thy-1.2 plus complement reduced their ability to protect. Tolerance of DH to HSV was induced by i.v. injection 7 days before subcutaneous immunization. Tolerized mice were unable to generate protective cells. Furthermore, tolerized mice contained suppressor T cells that suppressed not only DH but also the development of protective cells. Regulation of protective cells was shown to be virus specific, because mice tolerized with vesicular stomatitis virus (VSV) were not impaired in their ability to generate T cells that protected from HSV infection. The correlation between the TDH cell and cells that transfer protection from acute HSV infection is discussed. PMID- 2580007 TI - Arsonate-specific murine T cell clones. II. Delayed-type hypersensitivity induced by P-azobenzenearsonate-L-tyrosine (ABA-Tyr). AB - To study T cell idiotype expression at the functional level, we developed a hapten-specific delayed-type hypersensitivity (DTH) system by which we avoid the complication of anti-hapten antibody and which is specific only for the immunizing hapten, and not for conjugate specific determinants. Immunization with ABA-Tyr and challenge with ABA diazonium induced footpad swelling with the characteristics of DTH. Anti-ABA antibodies did not contribute to this reaction, as they were undetectable in mice immunized with ABA-Tyr. Furthermore, this ABA Tyr-specific DTH was under Ir gene control identical to that reported for ABA-Tyr specific lymphocyte proliferation. All mouse strains tested responded to ABA-Tyr except those of the b haplotype across the entire Ia region. In contrast, contact sensitivity induced by ABA diazonium was not under apparent Ir gene control, probably reflecting 1) different specificities of the induced T cells and 2) the production of anti-ABA antibodies that contribute to the footpad swelling via an Arthus reaction. Having shown that ABA-Tyr can induce T cells mediating DTH, we then examined ABA-Tyr-reactive T cell clones, propagated in vitro, for their ability to mediate DTH. Such clones elicited a response identical to that seen with in vivo immunization with respect to dose dependency, I-Ak restriction, and antigen specificity. PMID- 2580008 TI - Regulation of transplantation immunity in vivo by monoclonal antibodies recognizing host class II restriction elements. I. Genetics and specificity of anti-Ia immunotherapy in murine skin allograft recipients. AB - Antibodies reactive with host class II restriction elements exert profound regulatory effects on the immune response to a variety of antigenic stimuli, including tumor, autoantigens, and alloantigens. In the present studies, monoclonal reagents specific for host I-A and I-E glycoproteins were evaluated for their capacity to modulate transplantation immunity in a murine tail skin allograft system. It was found that treatment of A/J mice with 200 micrograms 10 3.6 hybridoma-derived anti-I-Ak antibody daily for 10 days resulted in an average twofold increase in the survival time of B10.A minor antigen-incompatible allografts. Similar results were achieved by using class I, but not H-2 mismatched, donor tissue. Specificity of antibody activity was demonstrated by the failure of isotype-matched reagents recognizing irrelevant class II or relevant class I H-2 antigens to influence rejection under these conditions. Although antibodies reactive with graft as well as host alloantigens provided the greatest degree of prolongation, interaction with host restriction elements alone was sufficient for the in vivo expression of regulatory activity. As in previous studies, anti-I-A treatment was associated with the development of antigen specific suppressor T cells that serve to dampen allograft immunity without altering secondary responses to unrelated antigens encountered after the initial treatment interval. These data suggest that anti-Ia immunotherapy may provide a clinically relevant approach toward the specific regulation of transplantation immunity in the appropriate donor-recipient combinations. PMID- 2580009 TI - The target minor H antigen for F1 cytotoxic T lymphocytes induced by Igh-congenic parental spleen cells is coded for by gene linked to H-2. AB - Graft-vs-host reaction (GvHR) induced in (B10.BR X CWB)F1 (BWF1; H-2k/b, Ighb/b) by i.v. injection with CWB (H-2b, Ighb) spleen cells resulted in complete suppression of cytotoxic T lymphocyte (CTL) responsiveness of the F1 host spleen cells (GvHR-associated immunosuppression). In contrast, GvHR induced in BWF1 mice with CSW (H-2b, Ighj; Igh-congenic to CWB) spleen cells did not affect CTL responsiveness of the F1 host spleen cells at all. The BWF1 hosts undergoing the CSW-induced GvHR generated anti-CSW CTL in their spleens, and the subsequent culture of such BWF1 spleen cells with CSW stimulator cells, augmented the CTL activity. The BWF1 anti-CSW CTL lysed both Con A- and LPS-induced splenic blasts from mouse strains carrying the Ighj allele in the context of self H-2Kb. However, determination of the Igh haplotype in the serum IgG and of the susceptibility of the splenic lymphocytes to the BWF1 anti-CSW CTL on backcross mice, which carry either Ighb/j or Ighb/b in the context of H-2b/b or H-2b/k, showed clearly that Ighj and the gene coding for the target antigen for the BWF1 anti-CSW CTL segregated at ratios close to 1:1. The study in which linkage between the gene(s) coding for the target antigen for the BWF1 anti-CSW CTL and H 2 was examined on CWB X (C3H X CWB)F1 backcross mice and (B10.BR X CSW)F1 X B10 mice demonstrated that the gene, most likely a single gene, coding for the target antigen for the BWF1 anti-CSW CTL is located at 8.5 +/- 4.3 cross-over units to the right or left of the H-2 complex. We designated the minor H antigen to be recognized by the BWF1 anti-CSW CTL as H-X+, and we discuss the distinction between the H-X+ locus and the other minor H loci on chromosome 17. PMID- 2580010 TI - Antigen processing requirements for T cell activation: differential requirements for presentation of soluble conventional antigen vs cell surface MHC determinants. AB - The present studies were undertaken to characterize the antigen-processing requirements involved in the responses to T cells to soluble antigen (antigen specific), to allogeneic cell surface MHC determinants (alloreactive), and to syngeneic MHC determinants (autoreactive). T cell clones were used that have dual cross-reactive specificities either 1) for self MHC plus soluble antigen and for allogeneic MHC products or 2) for syngeneic MHC and for allogeneic MHC, in order to permit comparison of the processing requirements for responses of the same T cell to distinct antigenic stimuli. The proliferative responses of antigen specific, Ia-restricted T cell clones to soluble antigens were sensitive to treatment of antigen-presenting cells (APC) with 125 to 250 microM chloroquine, a lysosomotropic agent previously shown to inhibit the processing of soluble antigens. In contrast, the same T cell clones were only minimally affected in their ability to respond to similarly chloroquine-treated APC expressing allogeneic MHC products. The responses of autoreactive T cell clones to syngeneic stimulating cells and their cross-reactive responses to allogeneic cells were both resistant to chloroquine treatment of stimulating cells. The failure of chloroquine to inhibit antigen presentation to autoreactive T cell clones suggests that these clones are specific for self Ia not associated with in vitro processed foreign antigen. Thus, chloroquine sensitivity distinguishes the in vitro antigen-processing requirements for presentation of the soluble antigens tested from the requirements for presentation of syngeneic or allogeneic cell surface MHC determinants to the same T cells. PMID- 2580011 TI - Susceptibility of cytotoxic T lymphocyte (CTL) clones to inhibition by anti-T3 and anti-T4 (but not anti-LFA-1) monoclonal antibodies varies with the "avidity" of CTL-target interaction. AB - To explore the role of the T3, T4, and LFA-1 molecules in high and low "avidity" interactions between SB2-specific cytotoxic T lymphocyte (CTL) clones and their targets, monoclonal antibody-mediated inhibition of cytotoxicity has been studied in experiments that vary the "avidity" of interaction in three different ways. 1) Previous results have been extended with respect to different CTL clones assayed on the same SB2-positive target cells. Differences between clones in susceptibility to anti-T3 inhibition paralleled variations in anti-T4 inhibition, and both correlated inversely with the "avidity" of the effector-target interaction (inferred previously from studies of conjugate dissociation). 2) A high "avidity" clone, 8.4, was identified that lysed not only SB2-positive cells but also cross-reacted on a few SB2-negative cells. Cold target inhibition studies confirmed the cross-reaction, and together with conjugate dissociation studies, indicated that cross-reaction to be of lower "avidity" than the specific recognition of SB2. Cross-reactive lysis was much more susceptible to inhibition by anti-T3 and anti-T4 than was specific lysis. 3) Anti-T3 and anti-T4 blocking was analyzed in the presence of anti-Ia antibody to reduce the amount of Ia antigen available on the target. Anti-T3 and anti-T4 antibody blocking was more efficient after the addition of anti-Ia antibody concentrations that (by themselves) produced minimal inhibition of lysis. As a control, anti-LFA-1 antibody blocking was analyzed in each of these three experimental systems that compare interactions of different "avidity"; minimal variation was observed in the efficiency of inhibition by anti-LFA-1. Thus, anti-T3 and anti-T4 inhibition correlates inversely with the "avidity" of that CTL-target interaction, but anti LFA-1 inhibition does not. PMID- 2580012 TI - A monoclonal anti-idiotypic antibody against a human monoclonal IgM with specificity for myelin-associated glycoprotein. AB - A human monoclonal IgM lambda antibody, directed against MAG, obtained from a patient with polyneuropathy associated with a gammopathy, was used as an immunogen to generate mouse monoclonal anti-idiotype antibodies. One hybridoma antibody, designated A8F2, reacts uniquely with the M-IgM of the patient, shows high affinity binding to the patient's M-IgM, and dose-dependently inhibits binding of the patient's M-IgM to its specific antigen MAG. Thus, A8F2 is a monoclonal anti-idiotype antibody that recognizes a region of the MAG binding site of the patient's IgM. Use of this anti-idiotype antibody in a competition RIA revealed the presence of naturally occurring anti-idiotype in the patient's serum. Because anti-idiotype antibodies may be part of a mechanism for down regulation of antibody production, the use of A8F2 to induce a specific immunosuppression should be considered. PMID- 2580013 TI - Presentation of myelin basic protein by murine cerebral vascular endothelial cells. AB - Guinea pig basic protein (GPBP)-sensitized murine lymph node cell cultures depleted of macrophages-monocytes (MO) are no longer able to proliferate in response to specific antigen in vitro. The addition of MO reconstitutes the response that can be blocked by the addition of syngeneic anti-I-A antisera. Freshly isolated murine central nervous system endothelial cells (CNS-EC) cannot replace MO for the presentation of GPBP antigen to specifically sensitized lymph node lymphocytes. The pretreatment of CNS-EC with concanavalin A-conditioned media resulted in the expression of Ia molecules and the consequent ability to present GPBP. Antigen presentation by CNS-EC could be blocked by anti-I-A antisera for the CNS-EC donor haplotype. PMID- 2580014 TI - Comparison of the expression of IL 2 receptors by human T and B cells: induction by the polyclonal mitogens, phorbol myristate acetate, and anti-mu antibody. AB - It is well established that IL 2 plays an important role in the proliferative response of T cells. Activated B cells were also recently found to express IL 2 receptors. The present studies were designed to compare qualitative, quantitative, and functional aspects of IL 2 receptor expression by activated T and B cells. Phorbol myristate acetate (PMA)-activated human T and small resting B cells and enhanced the expression of HLA-DR, HLA-DC/DS, and transferrin receptors while reducing Leu-4 antigen expression by T cells and IgM and IgD expression on B cells. PMA induced both T and B cells to express functional IL 2 receptors before cellular proliferation. Immune interferon did not participate in this induction. The m.w. of the IL 2 receptors expressed by activated T and B cells was identical: 54,000 to 59,000. Several differences were noted in the expression of IL 2 receptors by activated T and B cells on stimulation with PMA; T cells expressed IL 2 receptors sooner than B cells and in higher density, and the enhanced proliferative response of T cells to IL 2 was more difficult to inhibit with antibody to IL 2 receptors. In addition, IL 2 enhanced the expression of transferrin receptors by activated T cells but did not have a similar effect on activated B cells. Small B cells from the blood could also be induced by a mitogenic monoclonal anti-IgM antibody to express functional IL 2 receptors. Relatively large B cells in fresh blood samples were found to express functional IL 2 receptors and were capable of a modest proliferative response to IL 2. The intensity of the IL 2 receptor expression and the proliferative response by large B cells were enhanced by PMA stimulation. The data suggest that IL 2 receptors may play an auxiliary role in the B cell proliferative response and that IL 2 may exert its effect at a late phase in the B cell activation process. PMID- 2580016 TI - Isolation and characterization of a T suppressor factor by using a monoclonal antibody. AB - We have developed a monoclonal antibody to a T cell-derived suppressor factor (TsF) found in the serum of C57BL/6 mice hyperimmune to sheep red blood cells (SRBC). The antibody binds to the SRBC-specific TsF as well as to a TsF (TNP-TsF) from another system differing in both antigen specificity and MHC. It does not bind to unrelated proteins. The antibody inhibits the activity of the SRBC specific TsF in vitro. By using the monoclonal anti-TsF, we can isolate sufficient quantities of TsF to demonstrate that it fulfills several properties that have been attributed to TsF, namely, MHC restriction, antigen specificity, and the requirement for a second chain. Also, the purified TsF gives a single 68,000 dalton band upon SDS-PAGE gel analysis under reducing conditions. We conclude, therefore, that we have a method of the isolation of pure TsF, as well as a probe for the genetic, biochemical, and biologic analysis of TsF. PMID- 2580015 TI - Production of interleukin 3 and gamma-interferon by an antigen-specific mouse suppressor T cell clone. AB - An interleukin 2 (IL 2)-dependent, keyhole limpet hemocyanin (KLH)-specific, mouse suppressor T cell clone, 3D10, was found to produce interleukin 3 (IL 3) and gamma-interferon (IFN-gamma) in response to T cell mitogens Con A and PHA. Different from KLH-specific suppressor factor (TsF) that was spontaneously released into the medium when cultured in IL 2-containing conditioned medium, the production of IL 3 and IFN-gamma was induced by mitogenic stimuli. IL 3, IFN gamma, and TsF were separable by gel filtration through a Sephadex G-100 column, being recovered in fractions of m.w. 25,000 to 30,000, 45,000 to 50,000 and 60,000 to 70,000, respectively. On the other hand, minimum size of IL 3 and IFN gamma were shown to be about 25,000 and 20,000, respectively, by determining the lymphokine activities contained in the extracts from slices of SDS gels. These results indicate that IFN-gamma was present as a homodimer or hetero-complex with another carrier protein(s), whereas IL 3 was present as a monomeric form. A highly positive correlation (a correlation coefficient r = 0.96) between the titers of IL 3 and IFN-gamma produced by seven subclones derived from 3D10 was obtained, suggesting that IL 3 and IFN-gamma are induced by a process with a common mechanism. 3D10 also produced IL 3 and IFN-gamma when cultured with its specific antigen, KLH, in the presence of antigen-presenting cells. When Con A stimulated 3D10 cells were labeled with L-[35S]methionine, we found that at least three proteins, with m.w. of 35,000, 25,000, and 20,000, were specifically released into medium by the stimulation. The latter two may be IL 3 and IFN-gamma described above, respectively, because of the similarities in m.w. PMID- 2580018 TI - Oligosaccharide-dependent and independent Qa-1 determinants. AB - A contribution of N-linked oligosaccharides to determinants recognized by alloreactive cytotoxic T lymphocytes has not been demonstrated. Employing cloned CTL and tunicamycin, an inhibitor of protein glycosylation, we found that carbohydrate addition was required for the formation of two of six Qa-1 determinants. The other determinants were detectable on nonglycosylated Qa-1 molecules, similar to observations in most reports that allodeterminants on class I molecules are not dependent on glycosylation for serologic detection. Examination of TM-treated, Con A-activated lymphoblasts revealed a direct correlation between the determinants defined by the reactivity of CTL clones with target cells from four Qa-1 genotypes and their dependence on carbohydrate side chains for expression. Most anti-Qa-1b CTL clones recognized either a glycosylation-dependent determinant found only on Qa-1b cells or glycosylation independent determinants on both Qa-1b and Qa-1c cells. Similarly, clones that killed only Qa-1a cells recognized a glycosylation-independent determinant. However, clones reactive with both Qa-1a and Qa-1d cells recognized a glycosylation-dependent determinant on Qa-1a molecules and a glycosylation independent determinant on Qa-1d molecules. This result indicates that such clones recognize cross-reactive conformational determinants, not carbohydrate itself. Thus, N-linked oligosaccharides serve to stabilize the conformation of some Qa-1 determinants, but others remain intact on nonglycosylated molecules. The absence of similar data for H-2K/D/L molecules suggest that a reexamination of other class I antigens with cloned CTL is in order to determine whether Qa-1 molecules are unique. PMID- 2580017 TI - Stimulated rat T cell-derived inhibitory factor for cellular DNA synthesis (STIF). III. Effect on cell proliferation and immune responses. AB - Stimulated T cell-derived inhibitory factor for cellular DNA synthesis (STIF), a lymphokine produced from concanavalin A (Con A)-stimulated rat suppressor T cells, was examined for its inhibitory effect on various cultured cells and on in vitro immune reactions. STIF could inhibit the DNA synthesis of a variety of normal and neoplastic cells from rats, mice, and humans in a dose-dependent fashion. Kinetics studies revealed that STIF selectively inhibited cellular DNA synthesis after incubation for 12 hr, but after 36 hr, it also inhibited RNA and protein syntheses. The inhibited cellular DNA synthesis by 12-hr incubation with STIF was recovered after culturing the cells in STIF-free medium. The inhibitory effect of STIF on the DNA synthesis was not blocked by addition of a sugar (alpha methyl-D-mannoside, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, L-fucose, or L-rhamnose) in culture, as determined by using rat bone marrow cells. STIF inhibited proliferative responses of rat lymphocytes to T cell mitogens, Con A and phytohemagglutinin, and a B cell mitogen, lipopolysaccharide, as well as IL 2 dependent growth of cloned T572 cells. It could also inhibit both blastogenesis and cytotoxic T cell generation in allogeneic mixed lymphocyte reaction. The release of IL 2 from Con A-stimulated T cells was also inhibited by the added STIF in culture, as demonstrated from the finding that IL 2 activity was not detected in the supernatants even after an anion-exchange column chromatography. These results indicate that STIF could inhibit cellular DNA synthesis in a species-unrestricted manner and thus inhibits the proliferation of various normal and neoplastic cells, and that it could also inhibit lectin- or IL 2-dependent T cell proliferation as well as IL 2 production from T cells in in vitro immune reactions. PMID- 2580019 TI - The idiotypic characterization of the immune response to a defined epitope of a protein antigen and the specific in vivo suppression of the immune response to this epitope by anti-idiotypic antibodies. AB - C10, a monoclonal antibody of C3H.SW (CSW) origin, binds a decapeptide epitope of the tobacco mosaic virus protein (TMVP) representing residues 103-112 of the protein. In vivo administration of syngeneic anti-idiotypic antibodies to C10 (anti-C10) prior to immunization with TMVP suppressed the expression of antibodies to this decapeptide determinant in CSW mice without a significant reduction of the total anti-TMVP titer. The suppression could not be overcome with repeated challenges by antigen even 6 months after administration of anti C10. Analysis of anti-C10 showed that it contains antibodies to at least two idiotopes found on C10. One of these idiotopes, C10-Idm, is found on a very small fraction of CSW anti-TMVP antibodies capable of binding the decapeptide epitope. The other idiotope, C10-IdX, is found on most of the anti-TMVP antibodies which bind the decapeptide determinant. With synthetic analogues of the decapeptide determinant, a correlation was established between the presence of the C10-IdX and the fine specificity of the decapeptide-binding antibodies. The studies reported herein demonstrate that anti-idiotypic antibodies are potent modulators of the immune response and that the C10-IdX is important in the determination of the fine specificity of antibodies to this decapeptide epitope of TMVP. PMID- 2580020 TI - The molecular basis of the requirement for antigen processing of pigeon cytochrome c prior to T cell activation. AB - Antigen-induced activation of T lymphocytes that co-recognize Ia molecules has been shown to require an antigen-processing step by the presenting cell before T cell stimulation can occur. In this report, we demonstrate that antigen presentation of pigeon cytochrome c to an E kappa beta:E kappa alpha-restricted T cell hybridoma, 2C2, is inhibited by pretreatment of the antigen-presenting cells (APC) either with chloroquine or with fixation by paraformaldehyde. The chloroquine effect was partially reversible after 22 hr; the paraformaldehyde effect was not. In contrast, these treatments had little or no effect on the presentation of the carboxy-terminal cyanogen bromide cleavage fragment of pigeon cytochrome c, residues 81 to 104. There was at least a 50-fold greater potency of the fragment, as compared to that of the intact molecule, when paraformaldehyde fixed APC were used. In addition, the fixed cells did not present synthetic fragments of the cytochrome c that were nonstimulatory when presented by unfixed cells. This observation showed that the loss of potency, demonstrated previously for analogs of pigeon cytochrome c with single amino acid substitutions at positions such as 99, was not a consequence of an alteration in the rate of antigen-processing. This result is consistent with our earlier hypothesis that these residues are contact amino acids with the antigen-specific T cell receptor or the Ia molecule. The major goal of these experiments was to define the molecular transition that occurred as a result of antigen processing. To achieve this end, we tested a variety of pigeon cytochrome c molecules and fragments for their ability to be presented by paraformaldehyde-fixed APC. Apocytochrome c, the denatured form of the molecule with the heme removed, could not be presented by the fixed cells, nor could the fragment 60-104, derived by acid cleavage of the tryptophan at position 59. Both molecules stimulated an IL 2 response from the T cell hybridoma when unfixed APC were utilized, demonstrating that the conditions used to prepare these two molecules did not destroy their antigenic determinant. In contrast, carboxy-terminal fragments, both native and synthetic, ranging in size from 16 to 39 amino acids, were capable of stimulating in the presence of paraformaldehyde-fixed APC. In particular, the partial-digest cyanogen bromide fragment, residues 66 to 104, was only twofold less potent than the pigeon fragment 81-104.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2580021 TI - Interaction of monoclonal anti-peptide antibodies with lysozyme. AB - The interaction of monoclonal anti-peptide antibodies with the free peptide and its protein counterpart has been evaluated for hen egg white lysozyme and the peptide constituting residues 38 to 45. Fluorescence methodology has been developed for the measurement of association constants based on resonance energy transfer between the excited tryptophan of antibody and bound peptide ligand conjugated to a fluorescent probe. Five antibodies, four IgM and one IgG, have been assayed by ELISA, and have demonstrated binding to the adsorbed peptide alone, to the adsorbed lysozyme alone, or to both. Multivalent interaction with the adsorbed ligand is a key factor in the efficacy of binding. Measurement of binding constants in homogeneous solution, by equilibrium dialysis and energy transfer, demonstrated that lysozyme was bound to an IgG antipeptide antibody with an association constant (4 X 10(2) M-1) 200-fold less than that for the free peptide (8 X 10(4) M-1). It was also inferred for IgM that an association constant of the order of 10(2) M-1 was sufficient to effect selective interaction in a system providing multivalent interaction. The shared conformations between protein and peptide, implied by the specific reactivity of the anti-peptide antibody with the protein, points to structural fluctuations of the surface regions and residues of globular proteins. PMID- 2580022 TI - The human lymphocyte function-associated (HLFA) antigen and a related macrophage differentiation antigen (HMac-1): functional effects of subunit-specific monoclonal antibodies. AB - The structural and functional relations between the alpha- and beta-subunits of the human lymphocyte function-associated antigen (HLFA) and the human Mac-1 antigen (HMac-1) have been analyzed with the use of five monoclonal antibodies that react with these proteins. The specificities of these antibodies were examined by immunoprecipitation of proteins from 125I-labeled cells and purified HLFA and HMac-1 antigens. Three antibodies reacted with the Mr 95,000 common beta subunit of the proteins, and also co-precipitated the Mr 175,000 HLFA alpha subunit, the Mr 165,000 HMac-1 alpha-subunit, and a third polypeptide alpha subunit of Mr 150,000. The other antibodies were specific to noncross-reactive epitopes present on the alpha-subunits of HLFA or HMac-1. These specificities were confirmed in sequential immunoprecipitation studies. Peptide mapping showed that the beta-subunits of HLFA and HMac-1 were identical, whereas the two alpha subunits differed considerably. The HLFA alpha-subunit-specific monoclonal antibody inhibited phytohemagglutinin stimulation, the mixed lymphocytes reaction, cytolytic T lymphocyte-mediated killing, and tetanus toxoid stimulation, but did not affect natural killer cell-mediated killing or complement receptor type 3 function. The HMac-1 alpha-subunit-specific monoclonal antibody inhibited complement receptor type 3 function but had no effect on T cell or natural killer cell functions. Three monoclonal antibodies to the beta subunit inhibited all functions tested, including T cell, natural killer cell, and complement receptor type 3 activities. The results suggest that the functions of the HLFA and HMac-1 molecules may be determined by the alpha-subunit, and that the common beta-subunit also bears functionally important epitopes. PMID- 2580023 TI - Antibody-mediated alternative complement pathway activation resists inhibition by sialoglycolipids. AB - Although sialoglycolipids on liposome membranes were able to inhibit the activation of the alternative complement pathway (ACP) of guinea pigs mediated by trinitrophenylaminocaproyldipalmitoylphosphatidylethanolamine, they scarcely inhibited the ACP activation mediated by natural antibody to paragloboside (PG) inserted into the liposome membranes. Therefore, ACP activation was able to proceed regardless of the presence of sialoglycolipids on heterologous cell membranes when antibodies to constituents of the membranes were available. On the other hand, sialoglycolipids effectively inhibit undesirable ACP activation on self cell membranes, because little if any antibody is reacting on the self cell surface. Thus, the natural antibody reaction may effectively discriminate between self and non-self cell surface by cooperation with complement inhibitors on cell membranes such as sialoglycolipids. PMID- 2580024 TI - A 64,000 dalton matrix protein of human cytomegalovirus induces in vitro immune responses similar to those of whole viral antigen. AB - Human cytomegalovirus contains approximately 30 to 35 structural polypeptides. Although antibodies to several of these proteins are made during natural infection, their relationship to T cell recognition of this virus and subsequent control of infection is poorly understood. We have purified one of these proteins (HCMVgp64) that is found in abundance in infected cell lysates in order to delineate the relationship of single viral proteins to the immune response caused by the virus. HCMVgp64 induced T cell reactivity only in individuals with serologic evidence of past infection. In addition, HCMVgp64 elicited similar in vitro immune reactions as the whole virus including T cell proliferation, interleukin 2 production, and receptor expression as well as interferon production. These studies suggest that single proteins of HCMV such as HCMVgp64 are capable of inducing T cell responses and may be important in the development of immune reactivity to HCMV. PMID- 2580025 TI - Conserved group-specific epitopes of the circumsporozoite proteins revealed by antibodies to synthetic peptides. AB - The immunogenic properties of sporozoites are associated mainly with the circumsporozoite (CS) protein that covers the surface of mature sporozoites. This stage-specific protein has an immunodominant region with repetitive epitopes. Rabbits that are repeatedly immunized with sporozoites of Plasmodium knowlesi, a monkey malaria parasite, also recognize two synthetic peptides (N2 and C2) representing other polar domains of the CS protein. We show in this report that antibodies to the N2 and C2 synthetic peptides react not only with P. knowlesi but also with conserved regions of the surface membrane of other human, monkey, and rodent (but not avian) malaria sporozoites. Moreover, antibodies to N2 partially neutralize the infectivity of sporozoites of P. berghei, a rodent malaria parasite. In contrast, antibodies to synthetic peptides representing the repetitive epitope of P. knowlesi were strictly species specific. PMID- 2580026 TI - Detection of monoclonal antibodies specific for carbohydrate epitopes using periodate oxidation. AB - A method is described for determining whether particular monoclonal antibodies are specific for carbohydrate or non-carbohydrate antigenic determinants. In a model system consisting of the Lewis a human blood group determinant attached to either protein or lipid, mild periodate oxidation destroyed the carbohydrate determinant without altering protein or lipid epitopes. The technique was readily applied to antigens bound to plastic wells for ELISA, to nitrocellulose sheets for Western blots, and to thin layer chromatography (TLC) plates for TLC immunostaining. Mild periodate oxidation can prove useful during the early stages of hybridoma screening in order to select for or against anti-carbohydrate antibodies. PMID- 2580027 TI - Synthetic peptides as antigens: pitfalls of conjugation methods. AB - Peptide-carrier conjugates were prepared using 9 different synthetic peptides, 3 carrier proteins and 4 coupling reagents. Residues of the carrier protein that were modified by different coupling reagents (e.g., glutaraldehyde, carbodiimides, bis-diazotized benzidine) were found to elicit specific antibodies that reacted with unrelated carrier proteins treated with the same coupling agent. To demonstrate the presence of peptide antibodies in an antiserum raised against a peptide-carrier conjugate, it was necessary to use a antigen the peptide coupled to another carrier by means of a different coupling agent. Some of the commonly used conjugation methods were found to lead to conjugates of insufficient stability and sometimes also altered the antigenic properties of the peptide moiety. These difficulties can be overcome by additional control experiments designed to test the quality and the peptide-carrier conjugates. PMID- 2580028 TI - Two homogeneous immunoassays for pyridoxamine. AB - Protein conjugates of pyridoxal have been used to elicit anti-vitamin B6 antibodies in rabbits. These antibodies have been incorporated into 2 homogeneous assays systems, a spin immunoassay, using a paramagnetic derivative of the vitamin as ligand, and a fluorescence enzyme immunoassay, using beta galactosidase conjugated to vitamin B6 as the indicator molecule. These assay systems do not require fractionation steps, and could be the basis of analytical methodology for nutritional research or clinical diagnosis. PMID- 2580029 TI - [Fundamental study on the mechanisms of "cellular effect" in choriocarcinoma]. AB - The relationship between the growth potential and hCG secretion in 2 kinds of human choriocarcinoma cell lines was studied by using 5 kinds of anticancer drugs in strict in vitro conditions. The results are as follows. The hCG secretion per cell was enhanced when the DNA synthesis and growth of the cells were suppressed, irrespective of the human choriocarcinoma cell lines or anticancer drugs used. The hCG secretion per cell was suppressed when the rate of cell death increased. These results indicate that the transient rise in blood or urinary hCG values during chemotherapy ("cellular effect") is due to the suppression of DNA synthesis and growth of the cells and is not due to the result of the cell death. PMID- 2580030 TI - [Immunohistochemical localization of keratin and secretory component in carcinoma of the uterine cervix]. AB - Carcinoma of the uterine cervix is said to frequently show a combination of squamous epithelial and glandular epithelial characteristics. In the present study, immunohistochemical localization of keratin and secretory component (SC) was studied to clarify these characteristics of cancers of the cervix, and the following results were obtained. Demonstration of the localization of keratin and SC was useful in providing functional markers of the squamous and glandular epithelium of the cervix. In epidermoid carcinomas, the squamous epithelial character of the keratinizing carcinomas was strongest and decreased in the large cell non-keratinizing, followed by the small cell non-keratinizing carcinomas. The glandular character of these lesions decreased in the same order. Subclassification of CIS did not reveal any major changes with either kind of staining. So-called bipotential differentiation was found in 21% of the epidermoid, 53% of the adenocarcinomas and 13% of the CIS. In the clinical stages of epidermoid carcinomas, the stage I and II cases more frequently showed squamous characteristics than did the stage 0 cases. PMID- 2580031 TI - [Fundamental studies on arterial infusion chemotherapy for cervical cancer--with reference to the histological finding in infiltrating cancer and localization of the drugs in tissues]. AB - Preoperative arterial infusion of peplomycin was carried out on 15 cases of Stage I or II cancer of the cervix, and the value of arterial infusion chemotherapy with peplomycin and its efficacy as a preoperative therapy in cervical cancer were evaluated by analysis of (1) histological changes, (2) localization of the drug in tissue, and (3) tissue concentration of the drug in the completely resected tissues, with the following results: The chief histological change was a regression of cancer nests accompanied by degeneration and necrosis of cancer cells. This change was clearer at the head of infiltrating cancers than at their superficial layer or center. Peplomycin was localized with high activity at the disintegrated part of cancer nests, i.e., its activity was closely correlated to the severity of histological change. Time-course changes in its localization suggested the vessel wall----stroma----cancer as the route of its transport. The tissue concentration of peplomycin was maintained high over a long time. Particularly in the portio vaginalis, the time course decline of the concentration was gentle. From the above findings, arterial infusion of peplomycin was considered to be an effective method of chemotherapy for cervical cancer, and worth being tried as a preoperative therapy too. PMID- 2580032 TI - Toxic effects of chemicals on mouse post-blastocyst development--a trial to establish a testing system for embryotoxicity. AB - We established a new testing system to assess embryotoxic chemicals using cultured preimplantation mouse embryos. Randomly bred Crj:CD-1 (ICR) mice were used. Late blastocysts collected on Day 4 of pregnancy (plug day:Day 1) were exposed for 24 hrs. to various chemicals at varying concentrations. Morphological embryonic development, structural chromosome aberrations and sister chromatid exchanges (SCEs) were examined as the parameters of embryotoxicity. Treated embryos were then transferred to pseudopregnant foster mice for the evaluation of in vivo development. Of the morphological developmental endpoints in vitro, the formation of two-layer ICMs (inner cell masses) was the most sensitive to the toxicity of chemicals, followed by ICMs and trophoblast outgrowth. Threshold limit values were confirmed regarding morphological growth. However, exposure of embryos to lower concentrations than threshold enhanced the frequency of chromosome aberrations and SCEs. Transfer of embryos treated with the lower concentration of 4-nitroquinoline 1-oxide induced not only fetal wastage but also developmental retardation. 4-nitroquinoline 1-oxide was the most embryotoxic in mouse blastocysts, followed in order by mitomycin C, bleomycin, methylmercuric chloride, diethylstilbestrol, mercuric chloride and ochratoxin-A. This new testing system appears to be a sensitive method of measuring the direct effects of toxic chemicals which yields results in a short term. PMID- 2580033 TI - Soft tissue calcium and magnesium content in acute pancreatitis in the dog: calcium accumulation, a mechanism for hypocalcemia in acute pancreatitis. AB - The mechanism of hypocalcemia in acute pancreatitis remains unknown despite continued investigative work over the past several decades. Because acute pancreatitis is accompanied by multiple systemic manifestations and alterations of plasma membranes, the possibility that an abnormal translocation of calcium from extracellular to intracellular compartments could play a role in hypocalcemia of acute pancreatitis was investigated in dogs. Acute pancreatitis was induced by injecting bile into the pancreatic duct. Plasma calcium, magnesium, and amylase concentrations were determined. Calcium and magnesium contents were also measured in biopsy specimens of pancreas, liver, skeletal muscle, and kidney before and after induction of acute pancreatitis. As expected, hypocalcemia and hyperamylasemia occurred 6 hours after induction of pancreatitis, and persisted throughout the experiment, 13 to 25 hours. Plasma magnesium concentration fell at 6 and 18 hours, and returned to an almost normal level by the end of the study. A significant elevation in calcium content of pancreas (71%), liver (24%), and muscle (112%), and 25% reduction of calcium in kidney were observed in dogs with histologic signs of pancreatitis. However, tissue magnesium concentration fell in pancreas (18%) but remained unchanged in the other tissues investigated. No significant changes in any variables were detected in sham-operated animals. In another group of dogs in which the accessory pancreatic duct was not occluded when bile was injected, the histologic lesions were extremely mild, although the plasma calcium concentration and the pancreatic calcium and magnesium contents were altered just as much as in the severely affected dogs. Data suggest that the hypocalcemia of acute pancreatitis may be the result, at least in part, of accumulation of calcium in soft tissues. The decreased calcium content in kidney could be related to hypocalcemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580034 TI - Secretion of colony-stimulating factors by human monocytes and bone marrow cells after in vitro treatment with biological response modifiers. AB - The results of this study indicate that human interferons (hIFNs) may have bimodal effects in vitro on human myelopoiesis. Low concentrations of hIFN alpha (1-10 U/ml), hIFN beta (1-100 U/ml), and hIFN gamma (1 U/ml) stimulated in vitro increased secretion of colony-stimulating factors (CSF) by human blood monocytes, which induced growth and differentiation of granulocyte-macrophage progenitor cells. High concentrations of hIFNs alpha, beta, gamma (greater than 100 U/ml), however, had direct antiproliferative effects on granulocyte-macrophage progenitors. Both effects could be blocked by monoclonal antibodies against hIFN alpha and hIFN gamma, as well as by heteroantiserum against hIFN beta. Human IFNs did not appear to be involved in mediating the response to the chemically defined biological response modifiers (BRMs) poly ICLC (polyriboinosinic-polycytidylic acid poly-L-lysine) and BM 41.332 (2-cyano-1-[(2-methoxy-6-methyl-pyridin-3yl) methyl]-aziridine), since neutralizing antibodies against the human IFNs (anti IFN alpha, beta, gamma) did not block the poly ICLC and BM 41.332-induced secretion of CSF by human blood monocytes. In contrast to hIFNs, poly ICLC and BM 41.332 also stimulated adherent human mononuclear bone marrow cells to secrete CSF, which induced growth and differentiation of nonadherent granulocyte macrophage progenitors. The studies presented here thus support the concept that selected BRMs might be useful to stimulate in vivo secretion of myelopoietic growth factors and thereby promote granulocyte and monocyte/macrophage functions. PMID- 2580035 TI - Interferon produced endogenously in response to CSF-1 augments the functional differentiation of progeny macrophages. AB - The role of endogenously produced interferon alpha/beta in the functional maturation of newly derived mononuclear phagocytes was investigated. Addition of highly specific anti-interferon alpha + beta antiserum to murine marrow cultures stimulated with colony-stimulating factor-1 (macrophage growth factor) markedly suppressed the capacity of resulting progeny mononuclear phagocytes to ingest opsonized sheep erythrocytes (EAIgG). This impairment was corrected either by direct addition of interferon alpha + beta at a concentration in excess of that neutralized by the antiserum or by the addition of lesser amounts of interferon (33 U/ml) following removal of the anti-interferon from the cultures. Conditioned media from control colony-stimulating factor-stimulated cultures similarly reversed the impairment of maturation resulting from 5 days of growth in the presence of anti-interferon. This enhancement of EAIgG ingestion reflected upon the interferon activity in the conditioned media and was neutralized by anti interferon. Lastly, the endogenous interferon was found to enhance EAIgG ingestion by a majority of the mononuclear phagocyte progeny and not by a limited subpopulation. PMID- 2580036 TI - Anaphylatoxin C3a enhances mucous glycoprotein release from human airways in vitro. AB - Because C3a may be generated during the course of pulmonary inflammatory reactions, we investigated the ability of C3a to affect mucous glycoprotein (MGP) secretion from cultured human airways. C3a, but not C3a des Arg, caused a dose related increase in MGP release (maximal after 4-6 h), with as little as 15 micrograms of C3a per milliliter stimulating a 40% increase. The experimental evidence suggested that immunologically specific C3a was required for the secretagogue actions, as monospecific anti-C3a inhibited the reaction, as well as specifically absorbing the secretagogue from solution. Moreover, it appeared that C3a does not require mast cell activation, eicosanoid generation, or macrophage derived mucus secretagogue synthesis for its effect, since (a) no evidence of histamine release accompanied C3a-induced MGP release, and dibutyryl cAMP failed to affect C3a-induced MGP release, while reducing the actions of reversed anaphylaxis; (b) MGP release caused by C3a was not influenced by eicosatetraynoic acid or specific cyclooxygenase inhibitors, and no leukotrienes were detectable on the supernatants of C3a-stimulated airways; and (c) cycloheximide failed to affect C3a secretion-stimulating actions. Thus, C3a is a potent mucus secretagogue, and, possibly, acts directly as a glandular stimulant. It seems likely that C3a generated in the course of pulmonary inflammation might contribute to the mucus secretion associated with pulmonary infections. PMID- 2580037 TI - Gal-Gal pyelonephritis Escherichia coli pili linear immunogenic and antigenic epitopes. AB - The linear immunogenic and antigenic structure of E. coli Gal-Gal pili from the recombinant strain HU 849 was investigated with nine synthetic peptides corresponding to regions of the pilus sequence predicted to contain hydrophilic beta-turns. Five peptides, as bovine serum albumin conjugates, were found by anti HU 849 pilus serum and were thus designated "immunogenic epitopes." Peptides corresponding to R 25-38, R 38-50, and R 48-61 (which jointly comprise the single intramolecular disulfide loop), and R 103-116, were bound in low titer. A prominent immunogenic epitope was specified by a peptide corresponding to R 65 75. Four peptides, as thyroglobulin conjugates, elicited antisera in rabbits that bound intact HU 849 pili. These were designated "antigenic epitopes." Two prominent antigenic epitopes were localized to peptides corresponding to R 5-12 and R 93-104, whereas peptides corresponding to R 65-75 and R 119-131 represented two minor antigenic epitopes. None of the peptide antisera bound Gal-Gal pili from heterologous strains except anti-R 93-104 and anti-R 5-12. In 8 of the 10 Gal-Gal-binding pyelonephritis isolates tested, anti-R 5-12 detected a protein with an apparent molecular weight of 18,000 co-migrating with several Gal-Gal pili. Anti-R 93-104 detected a corresponding protein in 4 of 8 fecal and 7 of 12 pyelonephritis Gal-Gal-binding isolates; however, it also bound apparently unrelated proteins of higher molecular weight. PMID- 2580038 TI - Development of graft-vs.-host disease-like syndrome in cyclosporine-treated rats after syngeneic bone marrow transplantation. I. Development of cytotoxic T lymphocytes with apparent polyclonal anti-Ia specificity, including autoreactivity. AB - Lethally irradiated rats reconstituted with syngeneic bone marrow and treated with cyclosporine (CsA) for 40 d develop a graft-vs.-host disease-like syndrome (GVHD) after CsA therapy. We attempted to assess the development of autoreactivity in these animals. Results revealed that a majority of the animals with syngeneic GVHD develop autocytotoxic T lymphocytes of the OX8 phenotype. In addition to reactivity with self, these cells were capable of lysing appropriate target cells from a variety of different rat strains. The target antigens appeared to be class II major histocompatibility antigens, because lysis could be effectively blocked by an anti-Ia monoclonal antibody. Cold target inhibition studies indicated that one effector cell was capable of lysing various target cells, and provided evidence against a polyclonal activation of multiple anti-Ia reactive cells. These results suggested that the anti-class II autoreactive cell associated with syngeneic GVHD either recognizes a common class II determinant ("public" epitope) shared by multiple strains of rats, or was polyspecific with respect to "private" class II determinants. PMID- 2580039 TI - A subset of Ly-1 inducer T cell clones activates B cell proliferation but directly inhibits subsequent IgG secretion. AB - We find that a fraction of Ly-1+2- inducer T cell clones inhibits differentiation of memory B cells into IgG-secreting plaque-forming cells. Inhibition of secondary antibody responses was not the result of induction of Ly-2+ T suppressors. Instead, inducer cells directly inactivated B cells, requiring an antigen bridge as well as identity at the major histocompatibility complex (I-A) locus. The interaction between the inducer T cell clone and hapten-specific B memory cells results in an early proliferative response and subsequent failure of B cells to secrete antibody in response to T helper cell signals. Possible mechanisms for this novel type of B cell inactivation are explored. PMID- 2580040 TI - Cellular basis for neonatally induced T-suppressor activity. Primary B cell maturation is blocked by suppressor-helper interactions restricted by loci on chromosome 12. AB - The cellular mechanism and genetic restriction of neonatally induced HA-specific suppressor T (Ts) cells have been examined. The in vivo effect of these Ts cells on antibody production, primary B cell proliferation, B cell surface marker changes, and helper T (Th) cell priming during primary responses to HA have been determined. The results indicate that, although antigen-induced B cell proliferative responses and surface marker changes occur in the presence of Ts cells, differentiation to Ig secretion, and long-lived memory B cell production are prevented. Further, antigen-specific Th cell priming is completely ablated by Ts cells, suggesting that Ts act by preventing the delivery of Th signals required for both the later stages of primary B cell maturation, and the formation of memory B cell populations. Finally, in vivo cell mixing experiments using congenic mice indicate that this Ts-Th interaction is restricted by loci on mouse chromosome 12. PMID- 2580041 TI - Examination of the correlation of groupings in blood and semen. AB - The grouping of blood/saliva samples from a male so as to predict his semen groups is only justified if there is a strict correlation between the groupings in these body fluids. This correlation has been examined in the ABO, phosphoglucomutase (PGM1) and glyoxalase I (GLO) grouping systems in blood and semen samples collected from more than 250 individuals. Though no results proved inconsistent with this correlation, a number of semen gave inconclusive grouping results. Reasons for this are discussed as well as the relevance of the results to semen stain analysis. Semen amylase activities are also reported. PMID- 2580042 TI - Deuterium oxide and temperature effects on the properties of endplate channels at the frog neuromuscular junction. AB - The effects of deuterium oxide (D2O) and temperature on the properties of endplate channels were studied in voltage-clamped muscle fibers from the frog Rana pipiens. Studies were performed at temperatures of 8, 12, 16, and 20 degrees C. The single channel conductance (gamma) and mean channel lifetime (tau) were calculated from fluctuation analysis of the acetylcholine-induced end-plate currents. The reversal potential was determined by interpolation of the acetylcholine-induced current-voltage relation. The mean reversal potential was slightly more negative in D2O Ringer's (-7.9 +/- 0.1 mV [+/- SEM]) compared with H2O Ringer's (-5.2 +/- 0.6 mV, P less than 0.01). The single channel conductance was decreased in D2O. This decrease was greater than could be accounted for by the increased viscosity of D2O solutions, and the amount of the decrease was greater at higher temperatures. For example, gamma was 38.4 +/- 1.3 pS (+/- SEM) in H2O Ringer's and 25.7 +/- 1.0 pS in D2O Ringer's for a holding potential of 70 mV at 12 degrees C. The mean channel lifetime was significantly shorter in D2O, and the effect was greater at lower temperatures. There was not a strong effect of solvent on the temperature dependence of gamma. On the other hand, the temperature dependence of the reciprocal mean channel lifetime, alpha (where alpha = 1/tau), was strongly dependent upon the solvent. The single channel conductances showed no demonstrable voltage dependence over the range of -90 to 50 mV in both solvents. The reciprocal mean channel lifetime showed a voltage dependence, which could be described by the relation alpha = B exp(AV). The slope A was not strongly affected by either temperature or the solvent. On the other hand, the intercept B was a strong function of temperature and was weakly dependent upon the solvent, with most values greater in D2O. The D2O effects on alpha were what would be expected if they were due to the properties of D2O as a solvent (solvent isotope effects), while the D2O effects on gamma must also include the exchange of D for H in the vicinity of the selectivity filter (primary and/or secondary kinetic isotope effects). PMID- 2580045 TI - Characterization of a Salmonella typhimurium mutant defective in phosphoribosylpyrophosphate synthetase. AB - This study describes the isolation and characterization of a mutant (strain GP122) of Salmonella typhimurium with a partial deficiency of phosphoribosylpyrophosphate (PRPP) synthetase activity. This strain was isolated in a purE deoD gpt purin auxotroph by a procedure designed to select guanosine utilizing mutants. Strain GP122 had roughly 15% of the PRPP synthetase activity and 25% of the PRPP pool of its parent strain. The mutant exhibited many of the predicted consequences of a decreased PRPP pool and a defective PRPP synthetase enzyme, including: poor growth on purine bases; decreased accumulation of 5 aminoimidazole ribonucleotide (the substrate of the blocked purE reaction) under conditions of purine starvation; excretion of anthranilic acid when grown in medium lacking tryptophan; increased resistance to inhibition by 5-fluorouracil; derepressed levels of aspartate transcarbamylase and orotate phosphoribosyltransferase, enzymes involved in the pyrimidine de novo biosynthetic pathway; growth stimulation by PRPP-sparing compounds (e.g. guanosine, histidine); poor growth in low phosphate medium; and increased heat lability of the defective enzyme. This mutant strain also had increased levels of guanosine 5'-monophosphate reductase. This genetic lesion, designated prs, was mapped by conjugation and phage P22-mediated transduction at 35 units on the Salmonella linkage map. PMID- 2580046 TI - Purification and characterization of glucosyltransferases from Streptococcus mutans 6715. AB - A water-soluble glucan-synthesizing glucosyltransferase (GTase-S) and a water insoluble glucan-synthesizing glucosyltransferase (GTase-I) were purified from culture supernatant of Streptococcus mutans 6715 (serotype g) by ammonium sulphate precipitation, chromatofocusing on a Polybuffer exchanger PBE 94 column, and subsequent phenyl-Sepharose CL-4B or hydroxyapatite column chromatography. The GTase-S and GTase-I activities were purified 4019- and 4714-fold, respectively, and the molecular weights were calculated to be 160000 and 165000, respectively. GTase-S had a pH optimum of 5.0, a Km of 8.8 mM for sucrose in the presence of 20 microM-dextran T10, and an isoelectric point of pH 4.3. GTase-I had two pH optima of 5.0 and 7.0, Km values of 4.9 mM (at pH 5.0) and 7.0 mM (at pH 7.0), mM (at pH 7.0), and an isoelectric point of pH 4.9. Methylation analysis indicated that the water-soluble glucan produced by GTase-S was a highly branched 1,6-alpha-linked D-glucan with 1,3-linked glucose residues, and that the water insoluble glucan synthesized by GTase-I was composed of 1,3-alpha-linked glucose units. PMID- 2580044 TI - Simulated calcium current can both cause calcium loading in and trigger calcium release from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. AB - Skinned canine cardiac Purkinje cells were stimulated by regularly repeated microinjection-aspiration sequences that were programmed to simulate the fast initial component of the transsarcolemmal Ca2+ current and the subsequent slow component corresponding to noninactivating Ca2+ channels. The simulated fast component triggered a tension transient through Ca2+-induced release of Ca2+ from the sarcoplasmic reticulum (SR). The simulated slow component did not affect the tension transient during which it was first introduced but it potentiated the subsequent transients. The potentiation was not observed when the SR function had been destroyed by detergent. The potentiation decreased progressively when the slow component was separated by an increasing time interval from the fast component. The potentiation was progressive over several beats under conditions that decreased the rate of Ca2+ accumulation into the SR (deletion of calmodulin from the solutions; a decrease of the temperature from 22 to 12 degrees C). In the presence of a slow component, an increase of frequency caused a positive staircase, and the introduction of an extrasystole caused a postextrasystolic potentiation. There was a negative staircase and no postextrasystolic potentiation in the absence of a slow component. These results can be explained by a time- and Ca2+-dependent functional separation of the release and accumulation processes of the SR, rather than by Ca2+ circulation between anatomically distinct loading and release compartments. The fast initial component of transsarcolemmal Ca2+ current would trigger Ca2+ release, whereas the slow component would load the SR with an amount of Ca2+ available for release during the subsequent tension transients. PMID- 2580043 TI - Time and calcium dependence of activation and inactivation of calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. AB - Microprocessor-controlled changes of [free Ca2+] at the outer surface of the sarcoplasmic reticulum (SR) wrapped around individual myofibrils of a skinned canine cardiac Purkinje cell and aequorin bioluminescence recording were used to study the mechanism of Ca2+-induced release of Ca2+ from the SR. This Ca2+ release is triggered by a rapid increase of [free Ca2+] at the outer surface of the SR of a previously quiescent skinned cell. Ca2+-induced release of Ca2+ occurred under conditions that prevented any synthesis of ATP from ADP, was affected differentially by interventions that depressed the SR Ca2+ pump about equally, and required ionic conditions incompatible with all known Ca2+ releasing, uncoupled, partial reactions of the Ca2+ pump. Increasing the [free Ca2+]trigger up to an optimum increased the amount of Ca2+ released. A supraoptimum increase of [free Ca2+] trigger inactivated Ca2+-induced release of Ca2+, but partial inactivation was also observed at [free Ca2+] below that necessary for its activation. The amplitude of the Ca2+ release induced by a given increase of [free Ca2+] decreased when the rate of this increase was diminished. These results suggest that Ca2+-induced release of Ca2+ is through a channel across the SR membrane with time- and Ca2+-dependent activation and inactivation. The inactivating binding site would have a higher affinity for Ca2+ but a lower rate constant than the activating site. Inactivation appeared to be a first-order kinetic reaction of Ca2+ binding to a single site at the outer face of the SR with a Q10 of 1.68. The removal of inactivation was the slowest step of the cycle, responsible for a highly temperature-dependent (Q10 approximately 4.00) refractory period. PMID- 2580047 TI - Role of sex and early interferon production in the susceptibility of mice to encephalomyocarditis virus. AB - Adult female Swiss mice showed a greater resistance to intraperitoneal (i.p.) infection with encephalomyocarditis virus (EMCV) than male mice. This difference was not observed in weanling mice, in castrated adult mice or in adult mice injected intracerebrally. Administration of antibody to mouse interferon alpha/beta enhanced the virulence of EMCV for both sexes and no difference was then observed in susceptibility between male and female mice. Six h after EMCV infection, serum interferon titres were higher in adult female mice than in male mice. There was a close correlation between the early serum interferon titre (at 6 h) and survival of EMCV-infected mice. No differences in serum interferon titres were observed between male or female weanling mice or castrated adult mice. Potent preparations of exogenous interferon provided the same degree of protection against EMCV infection in male and female mice. We conclude that the more marked early interferon response of female mice to i.p. EMCV infection is one of the important factors underlying the differential susceptibility to EMCV. It is possible that the interferon system is also involved in the reported greater prevalence of picornavirus infections of men compared with women. PMID- 2580048 TI - Continuous production of interferon in normal mice: effect of anti-interferon globulin, sex, age, strain and environment on the levels of 2-5A synthetase and p67K kinase. AB - Two interferon-mediated enzymes, a 2-5A synthetase and a kinase that phosphorylates a 67 000 mol. wt. (p67K) protein were found at variable levels in different organs of mice. Among the different strains of mice included in this study, germ-free mice had the lowest levels of these enzymes. The levels of 2-5A synthetase and p67K kinase were enhanced significantly in all mice following treatment with mouse (alpha + beta) interferon. Here, we show that the presence of 2-5A synthetase and p67K kinase in different organs of normal mice (untreated) was due, at least in part, to a constant production of interferon under different physiological conditions. Accordingly, injection of normal mice with anti-mouse interferon (alpha + beta) globulin led to a significant decrease in the level of 2-5A synthetase and p67K kinase. In conventional mice (C3H/He), the level of both of these enzymes was higher in female than in male animals and was decreased with age or when such animals were reared isolated in a pathogen-free protected unit. The levels of 2-5A synthetase and p67K kinase were also decreased in normal mice following injection with a powerful antibiotic against a very wide spectrum of Gram-positive and Gram-negative bacteria. These results suggest that the production of interferon was induced continuously in normal mice. Such induction was mediated by both internal and external agents. PMID- 2580049 TI - Isolation of Daudi cells with reduced sensitivity to interferon. III. Interferon induced proteins in relation to the phenotype of interferon resistance. AB - The pattern of both constitutive and interferon-induced proteins was determined by two-dimensional gel electrophoresis in parental and interferon-resistant clones of Daudi cells in relation to the phenotype of interferon resistance. The complement of constitutive proteins present in clones DIF3, DIF8, DIF9 and DIF10 appeared to be identical to that of parental Daudi cells even though these cells were resistant to both the antiviral and anti-proliferative actions of interferon. Treatment of Daudi cells for 20 h with 10(3) reference units/ml of electrophoretically pure human interferon-alpha resulted in the induction of 15 proteins of molecular weights ranging from 15000 to 62000 detected after a 4 h labelling period with L-[35S]methionine. A number of these proteins were also induced in interferon-resistant clones of Daudi cells although some of these proteins appeared later and in smaller amounts than in the interferon-treated parental cells. However, seven proteins with molecular weights ranging from 18000 to 58000 which were induced by interferon in parental Daudi cells were not induced in any of the four interferon-resistant clones, suggesting that the phenotype of interferon resistance of these cells may be related to a reduction or absence of certain interferon-induced protein(s). PMID- 2580051 TI - Comparison of RNA from healthy and scrapie-infected hamster brain. AB - Density gradient fractions prepared from healthy or scrapie-infected hamster brain tissue enriched in plasma membrane vesicles were treated with nucleases prior to phenol extraction and ethanol precipitation. The recovered nucleic acids were 3' end-labelled and run on one-dimensional polyacrylamide gels. Autoradiography revealed the presence of low molecular weight RNAs (4S) in both healthy and scrapie samples. Two-dimensional fingerprint analysis indicated that the RNAs isolated from scrapie-infected hamsters contained oligonucleotides that were not present in RNAs isolated from healthy hamsters. PMID- 2580050 TI - Isolation of monoclonal antibodies specific for Rous sarcoma virus structural, polymerase and transforming proteins and their use for the study of mutant virus infected cells. AB - Monoclonal antibodies were developed that are specific for Rous sarcoma virus structural, polymerase (reverse transcriptase) and transforming proteins. The monoclonal antibodies were shown to bind to purified virus proteins in an indirect 125I-labelled Protein A binding assay suitable for screening even very large numbers of hybridomas. Additional tests for specificity included radioimmunoprecipitation of purified virus structural proteins P12 and P27, of reverse transcriptase subunits alpha and beta, and of the transforming protein pp60v-src. Pilot immunofluorescence and protein kinase assays of the expression of virus proteins in avian and mammalian cells infected by wild-type virus as well as by temperature-sensitive, transformation-defective virus mutants revealed that synthesis of virus structural and transforming proteins is hardly affected by changes in temperature, whereas the pp60v-src-associated kinase activity is temperature-sensitive in cells infected by most, but not all the virus mutants. PMID- 2580053 TI - Human interferons alpha and beta have more potent priming activities than interferon gamma. AB - The priming activities of human IFN-alpha, IFN-beta and IFN-gamma were compared on the same antiviral basis using human buffy coat leukocytes stimulated with Sendai virus or concanavalin A (Con A) to produce IFN-alpha or IFN-gamma, respectively. Pretreatment of leukocytes with any type of IFN enhanced their IFN alpha and IFN-gamma production, but IFN-alpha and IFN-beta had more potent priming activities than IFN-gamma. IFN-alpha and IFN-gamma did not potentiate the priming activity of each other in either the IFN-alpha or the IFN-gamma producing system. Pretreatment of leukocytes with relatively high doses of IFN-alpha or IFN beta (1000 to 3000 IU/ml) resulted in a 40- to 50-fold increase in the IFN-gamma production of Con A-stimulated leukocytes. This observation will be of use in producing IFN-gamma with a high titre. PMID- 2580052 TI - Interferon induction by viruses. XII. Inhibition of protein synthesis renders aged chick embryo cells refractory to interferon induction. AB - The initial stages of interferon induction in mouse L cells do not require protein synthesis; all steps in the induction process up to and including the transcription of interferon mRNA occurred in the presence of inhibitors of protein synthesis. In contrast, interferon induction in primary chick embryo cells aged in vitro does require a reaction that depends upon protein synthesis, unique in that it is not required for virus replication or the action of interferon. PMID- 2580054 TI - Antibody response to type-common and type-unique epitopes of herpes simplex virus polypeptides. AB - Herpes simplex virus type 1 (HSV1) and type 2 (HSV2) polypeptides with type common and type-unique epitopes were identified using cross-adsorbed hyperimmune rabbit sera and Western blotting techniques. Twelve HSV1 and fourteen HSV2 polypeptides with type-specific epitopes were identified. Cross-adsorbed human sera reacted to a subset of the type-specific epitopes defined by rabbit sera. Human sera with both HSV1- and HSV2-specific antibodies were identified by their reaction to HSV1-type-specific epitopes after adsorption with HSV2, and HSV2-type specific epitopes after adsorption with HSV1. Mixing experiments demonstrated the sensitivity of this assay for detecting HSV2-type-specific antibody in the presence of HSV1 antibody. This technique has proven useful in the study of immune response to individual HSV polypeptides during human HSV infections, while the presence of these type-unique epitopes on HSV polypeptides allows for the detection of type-specific antibodies in human sera. PMID- 2580055 TI - AN6520 Ag: an antigen purified from liver with non-A, non-B hepatitis. AB - An extract prepared from the liver of patient with chronic non-A, non-B (NANB) hepatitis was found to produce a precipitin line in immunodiffusion with a serum from a multiply transfused patient and those from patients convalescent from NANB hepatitis. The antigen was purified by gel filtration and density gradient centrifugation. The antigen had a buoyant density of 1.16-1.20 g/cm3 in cesium chloride, a sedimentation coefficient (S20,w) of 51.5, and a molecular weight of larger than 1.5 X 10(6) daltons. Electron microscopic examination revealed particles 29-34 nm in diameter (average 31.5 nm), which could be agglutinated by the specific antiserum. We developed a reverse passive hemagglutination (R-PHA) and a passive hemagglutination (PHA) technique for detection of the new antigen and antibody, respectively, and applied these to human sera. Antibody to the antigen was detected in 19/28 (67.9%) convalescent sera of NANB hepatitis. This prevalence was significantly higher than those found in convalescent sera of type A hepatitis patients (2/17 = 11.8%), type B hepatitis patients (2/15 = 13.3%), and normal blood donors (9/129 = 7.0%) (p less than 0.01); and the prevalence in hepatitis A and B patients did not differ significantly from that of normal donors. Furthermore, most (66.7%) of the cases of NANB hepatitis endemic in Shimizu City, Japan, showed clear seroconversion with respect to this antibody. These results suggest that the new antigen/antibody system is associated with NANB hepatitis. PMID- 2580057 TI - First evidences of the formation of a vanadyl(IV) complex of bleomycin. AB - Results of visible/ultraviolet and infrared spectroscopic measurements, as well as chemical evidence are presented which support the formation of a 2:1 bleomycin VO2+ complex. The information obtained also allows some considerations concerning the probable coordination sphere of the vanadyl ion. PMID- 2580056 TI - Female exhibitionism. AB - Although genital exhibitionism has traditionally been almost exclusively associated with males, similar behavior may occur in certain women with a particular set of life circumstances and precipitants. A case report is presented of a woman whose emotional deprivation led to feelings of rejection and the inability to develop empathic relationships. Her self-esteem relied on success in her profession, and when she lost her position, she sought validation through exhibitionism. Despite the widely held view that genital exhibitionism producing arousal and stimulation in the subject occurs only in men, this case demonstrates that such phenomena may exist in women as well. PMID- 2580058 TI - Pantomime comprehension and ideomotor apraxia. AB - In a prior study it was shown that apraxic patients with posterior infarctions that included the parietal lobe could not discriminate between gestures. In this study these observations were replicated using a nonverbal paradigm in which the subjects did not have to discriminate between gestures, but instead had to comprehend their meaning. Pantomimed acts on videotape were shown to six apraxic aphasic patients, seven nonapraxic-aphasic patients, and six normal subjects. Four drawings were also shown, one of which matched the pantomime (for example, if the pantomime was of hammering, one drawing was of a nail and three were foils). Subjects responded by pushing a button corresponding to the desired picture. The apraxics made more errors than the aphasics or controls. PMID- 2580059 TI - Effect of ionising radiation on the axon reaction of mouse anterior horn motor neurons. A histological and immunocytochemical study using a monoclonal antibody to neurofilament protein. AB - The changes taking place in irradiated central nervous tissue prior to the onset of delayed radionecrosis are poorly understood, but functional abnormalities occurring during the latent interval after irradiation are likely to be of importance. In order to investigate functional disturbances in neurones during this period, unilateral sciatic nerve crush was performed in mice following sub lethal X-irradiation of the lumbar spinal cord. Alterations in the axon reaction of anterior horn cells were studied using a monoclonal antibody to neurofilament protein. With irradiation immediately prior to crush, the normal, well-defined increase in perikaryal neurofilament protein was significantly diminished, although there was no concurrent radiation necrosis and no alterations were seen in contralateral neurones with intact distal axon processes. The effect was more marked in neurones irradiated one month prior to nerve crush, and in the non irradiated nerve crush region regeneration was delayed, with diminished neurofilament protein in the regenerating axons. These observations indicate that ionising radiation can progressively impair the ability of neurones to synthesise neurofilament protein during distal axon regeneration. This may result from inadequate repair of radiation induced DNA strand-breaks, but may also follow more generalised damage to protein transcription enzymes and RNA metabolism. PMID- 2580060 TI - Multiple system atrophy with neuronal intranuclear hyaline inclusions. Report of a case and review of the literature. AB - A 31/2-year-old girl presented with frequent falls. She had an unsteady gait, delayed behavioural development absent tendon reflexes and in the legs decreased strength tone and equivocal plantar responses. She then developed ataxia, nystagmus, choreoathetosis, cranial nerve palsies, diminished strength and tone in the arms, sensory deficit in the limbs and autonomic nervous system dysfunction. She became progressively less responsive and succumbed at the age of 63/4 years. Examination of the central, peripheral and autonomic nervous system showed ubiquitous neuronal intranuclear hyaline inclusions and neuronal loss in several sites. PMID- 2580061 TI - Humoral immune responses to myelin basic protein, cerebroside and ganglioside in chronic relapsing experimental allergic encephalomyelitis of the guinea pig. AB - Titers of serum antibodies to myelin basic protein, cerebroside and ganglioside were determined in chronic relapsing experimental allergic encephalomyelitis in strain 13 guinea pigs at various intervals after inoculation with whole central nervous system (CNS) tissue. Levels of antibodies to cerebroside and ganglioside were higher in the animals with paralysis than those without paralysis during the early chronic stage. In the late chronic stage, these antibodies were still at high levels, but none of the levels correlated with clinical activity. Levels of antibody to cerebroside were significantly related to the amount of demyelination. The humoral response to the CNS antigens was monophasic, although the clinical course was polyphasic. Another factor seems to be required for clinical relapses in this animal model. PMID- 2580062 TI - A possible nonimmunologic biological response to neoplasia: the tumor fibrovascular stroma. PMID- 2580063 TI - Interferon-induced transfer of natural cytotoxic activity between human leukocytes. AB - Interferon (IFN) caused the transfer of natural cytotoxic activity between human leukocytes in a syngeneic system. The transfer of cytotoxic activity was found to be dependent on the cell density and was in proportion to the IFN concentration. Human immune-type IFN (IFN-gamma) was more efficient than IFN-alpha or IFN-beta in eliciting the transfer of cytotoxic activity. The transfer occurred with IFN gamma preparations of various specific activities and with recombinant IFN-gamma. The transferred activity had the characteristics of an IFN-induced antiviral state, in that it was blocked either by actinomycin D or by prevention of cell contact. Specific antibodies to IFN had no effect on the transfer of cytotoxic activity. Protection of mouse target cells from human cytotoxic activity could also be transferred from IFN-induced human foreskin fibroblasts (HFF) insensitive to cytotoxic activity to the cytotoxic-sensitive mouse cells. The transfer of protection was highly efficient at ratios of one HFF cell to 16 mouse target cells. The transfer of cytotoxic activity, and protection from cytotoxic activity, may represent a mechanism for amplification of the IFN system as a host defense against viral-infected or tumor cells. PMID- 2580064 TI - High-dose methotrexate-induced neurotoxicity associated with elevation of CSF myelin basic protein. PMID- 2580066 TI - Treatment with 6-hydroxydopamine and colchicine decreases nerve growth factor levels in sympathetic ganglia and increases them in the corresponding target tissues. AB - A two-site enzyme immunoassay was used to determine the nerve growth factor (NGF) contents of sympathetic ganglia and their corresponding target tissues in adult rats. The destruction of sympathetic nerve terminals by 6-hydroxydopamine (6 OHDA) and the blockade of axonal transport by colchicine resulted in a rapid increase in the NGF levels of sympathetically innervated organs and a rapid decrease in the sympathetic ganglia. NGF levels in heart atrium, heart ventricle, submandibular gland, and iris increased 2- to 4-fold 12 hr after injection of 6 OHDA, whereas the NGF contents of stellate and superior cervical ganglia dropped to a minimal level of 3 to 4% of control 24 hr after injection. Twelve hours after treatment with colchicine the NGF levels in sympathetically innervated organs increased 2- to 3-fold, whereas the NGF contents of sympathetic ganglia fell to one-third of control values. The half-lives of NGF in the superior cervical and stellate sympathetic ganglia were 4.5 and 4.8 hr, respectively, as determined by the decrease of NGF content after treatment with 6-OHDA. These results indicate that the synthesis of NGF is normally confined to the innervated target organs with no significant contribution of ganglionic cells. This is consistent with the concept that NGF acts as a retrograde messenger between target organs and innervating sympathetic neurons. PMID- 2580067 TI - Retrograde axonal transport of endogenous phospholipids in rat sciatic nerve. AB - Anterograde axonal transport of phospholipids occurs at a rate of several hundred millimeters per day. However, although labeled precursors are incorporated into phospholipids in the neuronal cell bodies within several hours, these newly synthesized phospholipids are committed to transport over a much longer period of time. Thus, maximal accumulation of radioactive lipids in axons and nerve endings does not occur for several days (e.g., 4 to 7 days in rat optic tract and sciatic nerve). We have now investigated the retrograde axonal transport of endogenous phospholipid molecules in sensory neurons of rat sciatic nerve. Labeled phospholipids were delivered to axons and nerve endings of these cells by anterograde axonal transport following injection of [2-3H] glycerol into the L5 dorsal root ganglion. At various times following precursor injection two ligatures, 9 mm apart, were applied to the mid-thigh region of the sciatic nerve. Animals were sacrificed 3 to 48 hr after nerve ligation, nerves were dissected and sectioned into 5-mm segments, and phospholipid radioactivity in each segment was determined. The time-dependent accumulation of labeled phospholipids distal to the distal ligature demonstrated their retrograde axonal transport. The time course of retrograde transport for these phospholipids was more prolonged and peaked several days later than the time course for the anterograde transport phase. Further information regarding the relationship between radioactive phospholipids arriving at the nerve endings by anterograde transport, and their subsequent "turn-around" and retrograde transport back to the nerve cell bodies, was obtained by analyzing the phospholipid class label distribution of both of these transport phases at various times following precursor injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580068 TI - Gating kinetics of nonjunctional acetylcholine receptor channels in developing Xenopus muscle. AB - The development of nonjunctional acetylcholine (ACh) receptor gating kinetics was studied in myotomal muscle of Xenopus laevis by spectral analysis of ACh-induced noise. The results are consistent with the idea that there is a developmental shift in relative numbers of receptors with fast and slow gating kinetics. For about the first 20 hr following the onset of ACh sensitivity, the majority of channel openings contributing to the ACh noise were slow, having an apparent mean open time of about 3 msec. Shortly before the time of hatching, there began to appear a significant contribution to the noise from channels having a mean open time of less than 1 msec. The relative amount of fast channel activity increased during the 2 days following hatching, and by the age of maturity of the myotomal synapse, most of the ACh noise arose from fast channel activity. A comparison of nonjunctional kinetics with synaptic currents at maturity suggests that the control of channel gating time is similar at junctional and nonjunctional regions. PMID- 2580065 TI - Simulation of synaptic depression, posttetanic potentiation, and presynaptic facilitation of synaptic potentials from sensory neurons mediating gill withdrawal reflex in Aplysia. AB - The defensive gill-withdrawal reflex in Aplysia has proven to be an attractive system for analyzing the neural mechanisms underlying simple forms of learning such as habituation, sensitization, and classic conditioning. Previous studies have shown that habituation is associated with synaptic depression and sensitization with presynaptic facilitation of transmitter release from sensory neurons mediating the reflex. The synaptic depression, in turn, is associated with a decrease in Ca2+ currents in the sensory neurons, whereas presynaptic facilitation with increased Ca2+ currents produced indirectly by a decrease in a novel serotonergic sensitive K+ current. The present work represents an initial quantitative examination of the extent to which these mechanisms account for each of these types of synaptic plasticity. To address these issues a lumped parameter mathematical model of the sensory neuron release process was constructed. Major components of this model include Ca2+-channel inactivation, Ca2+-mediated neurotransmitter release and mobilization, and readily releasable and upstream feeding pools of neurotransmitter. In the model, release of neurotransmitter has a linear function of Ca2+ concentration and is not affected directly by residual Ca2+. The model not only simulates the data of synaptic depression and recovery from depression, but also qualitatively predicts other features of neurotransmitter release that it was not designed to fit. These include features of synaptic depression with high and low levels of transmitter release, posttetanic potentiation, a steep relationship between action potential duration and transmitter release, enhanced release produced by broadening the sensory neuron action potential (presynaptic facilitation), and dramatic synaptic depression with two closely spaced tetraethylammonium (TEA) spikes. The model cannot account fully for synaptic depression with empirically observed somatic Ca2+-current kinetics. Rather a large component of synaptic depression is due to reduction to the pools of releasable neurotransmitter (depletion). In the model when spike durations are greater than 15-20 ms, spike broadening produces little facilitation. However, when spike durations are more physiological, spike broadening leads to enhanced transmitter release. PMID- 2580069 TI - Hepatic level of rat albumin messenger RNA is influenced by factors other than dietary protein. AB - Dot hybridization of messenger RNA (mRNA) and complementary DNA (cDNA) has been used to measure the relative levels of albumin and alpha-fetoprotein mRNA in liver of rats fed for 5 d a fat-free (carbohydrate-rich) diet, a high fat diet or a basal diet, all three of which were isonitrogenous. The level of albumin mRNA in rats fed the fat-free (carbohydrate-rich) diet was 30 to 45% of the level in animals fed the basal 4% fat diet. The concentration of another mRNA, that for alpha-fetoprotein, remained unchanged. It has been established by others that albumin mRNA levels and albumin synthesis are diminished in response to low levels of dietary protein. We show that albumin mRNA levels are lower than those observed in animals fed the basal 4% fat diet, even when dietary protein is adequate (30% wt/wt), if the nonprotein calories are derived solely from carbohydrate. PMID- 2580070 TI - Identification of basement membrane components and intermediate filaments in calcifying epithelial odontogenic tumors. AB - An immunohistochemical technique was used on paraffin-embedded tissues of four cases of calcifying epithelial odontogenic tumors (CEOT). These studies were performed to gain an additional understanding of the nature of amyloid-like deposits in these tumors. For these studies antibodies to Type IV collagen, laminin, and the five classes of intermediate filament proteins were employed. In all of the tumors examined basement membrane components and intermediate filament proteins (cytokeratin) were demonstrated both in the epithelial tumor islands and within the extracellular amyloid-like deposits. Antibodies to vimentin intermediate filaments were localized only in the stromal fibroblasts. Limited proteolysis or the use of a chaotropic agent was required to express the antigenic determinants present. These studies substantiate the presence of basement membrane components in the amyloid-like deposits of CEOT. In addition, these extracellular deposits are shown to be heterogenous in composition by the immunohistochemical demonstration of cytokeratin intermediate filament proteins. PMID- 2580071 TI - Serotonin in fore-gut carcinoids. A survey of 60 cases with regard to silver stains, formalin-induced fluorescence and serotonin immunocytochemistry. AB - A series of 60 fore-gut carcinoid tumours was examined with regard to serotonin content after application of three different techniques, namely: the argentaffin reaction, formalin-induced fluorescence according to Falck-Hillarp and immunocytochemistry with monoclonal antibodies to serotonin. To evaluate the staining-fluorescence of individual tumour cells, the methods were applied to identical tumour sections. Twelve tumours demonstrated serotonin-immunoreactive cells, six of which were also argentaffin. Four tumours contained argentaffin cells but no serotonin-immunoreactivity. With the use of all three techniques, three types of tumour cells occurred, namely: serotonin-immunoreactive, non argentaffin and non-fluorescence cells, serotonin-immunoreactive, argentaffin and fluorescent cells, and non-serotonin immunoreactive, argentaffin and non fluorescent cells. The first (serotonin-immunoreactive) cell type was most frequently found in the tumours. One gastric carcinoid in which the argentaffin cells exceeded the serotonin-immunoreactive cells, a positive reaction was found with the modified Warthin-Starry reaction for demonstrating melanin. Since none of the techniques used for visualization of serotonin in endocrine tumours is unquestionably specific and since they do not give identical results, it is indicated that for a more accurate identification of serotonin in fore-gut carcinoid tumours, a positive reaction with at least two of the applied techniques is desirable. PMID- 2580072 TI - Effect of valproic acid on 5-hydroxytryptamine turnover in mouse brain. AB - The effect of the antiepileptic drug valproic acid (di-n-propylacetic acid, 200 mg kg-1) on brain 5-hydroxytryptamine (5-HT) synthesis during monoamine oxidase inhibition by pargyline hydrochloride (120 mg kg-1) was studied in mice. Valproic acid increased 5-HT synthesis and elevated 5-hydroxyindoleacetic acid level in brain indicating that turnover of 5-HT is increased. The possible significance of this effect in relation to anticonvulsant action of valproic acid is discussed. PMID- 2580074 TI - Isolated pediculosis. PMID- 2580073 TI - Evidence for the involvement of endogenous substance P in the motor effects of capsaicin on the rat urinary bladder. AB - [pro4,trp7,9,Leu11]SP-(4-11), a substance P (SP) antagonist, selectively antagonized contractions produced by either capsaicin or SP on the rat isolated urinary bladder. These experiments provide direct evidence indicating that the motor effects of capsaicin on rat urinary bladder are attributable, at least in part, to the release of endogenous SP. PMID- 2580075 TI - Effects of 2-nicotinamidoethyl nitrate on agonist-sensitive Ca++ release and Ca++ entry in rabbit aorta. AB - The effects of 2-nicotinamidoethyl nitrate (SG-75) on norepinephrine (NE)- and KCI-induced responses in rabbit aorta were quantitated, correlated with 45Ca studies and compared with the effects of nifedipine (NIF) on similar parameters. NE- and KCI-induced dose-response relationships were differentially depressed by SG-75 (NE much greater than KCI) and NIF (KCI much greater than NE). Responses to KCI were relatively insensitive to prior SG-75, yet moderately relaxed by subsequent SG-75. Conversely, NIF markedly inhibited and completely relaxed similar responses. Responses to NE were relaxed and inhibited with SG-75, but unaffected by NIF. Responses to NE in La or O-Ca++ + ethylene glycol bis(beta aminoethyl ether)N,N'-tetraacetic acid plus D600 (with and without KCI) solutions were phasic, reduced by SG-75 and insensitive to NIF. NE-dependent, Ca++-induced responses in a O-Ca++ + ethylene glycol bis(beta-aminoethyl ether)N,N' tetraacetic acid plus D600 solution (with and without KCI) were attenuated by SG 75. Equilibrated (60 min) La -resistant (residual), high apparent affinity Ca++ binding was increased 26% with SG-75 and decreased 34% with NIF, yet neither altered the rate of exchange (10 min). Rate of exchange at low apparent affinity, residual sites was increased 21% by SG-75 without altering equilibrated values, whereas NIF reduced equilibrated values 11%, without affecting rate. NE reduced, SG-75 + NE augmented and NIF + NE decreased, in an additive fashion, high apparent affinity, residual bound Ca++. Residual Ca++ binding at low apparent affinity sites was increased with 160 mM substituted KCI (380%). This increase was only partially inhibited with SG-75, and eliminated by NIF. Net Ca++ efflux was persistently slowed by SG-75 and unaltered by NIF. The primary effects of SG 75 appear to be depression of Ca++ release and inhibition of receptor-operated (potential-independent) Ca++ entry, with limited attenuation of voltage-dependent Ca++ entry. NIF primarily inhibits voltage-dependent Ca++ entry. PMID- 2580076 TI - Actions of Ba++ on ionic currents of the guinea-pig taenia coli. AB - The actions of Ba++ have been studied on short segments of the guinea-pig taenia coli voltage-clamped by a double sucrose-gap method. Ba++ slows the rising phase of the action potential, increases the peak amplitude and delays the repolarization with a long plateau. Ba++ carries charges through the normally Ca++ channel and directly influences both the magnitude (Ia) and the reversal potential (Ea) of the early current. The activation is slowed slightly, but the inactivation is slowed markedly. The voltage-conductance relation is shifted toward more negative voltages in Ba++, and the maximum conductance, ga, is increased significantly. Ba++ displaces the late outward current toward more positive voltages. The voltage-conductance relation is shifted by some 20 mV in 2.5 mM, and increasingly larger amounts with increasing [Ba++]o. The maximum conductance, gb, and the reversal potential (Eb) are not altered. Co++ blocks the inward Ba++ current and reverses the effects of Ba++ on the potassium conductance. Ca++ competes with Ba++. The apparent Kd for Ba++ is 6 mM and the apparent Kd for Ca++ is 0.6 to 1.0 mM. When Ca++ is added, the plateau of the long action potential in Ba++ is shortened by one-half. The effects of Ba++ are ascribed to some screening effect on fixed negative charges on the inside and outside surfaces of the membrane. PMID- 2580077 TI - Identification of delayed potassium and calcium currents in the rat sympathetic neurone under voltage clamp. AB - Post-ganglionic neurones of the isolated rat superior cervical ganglion were studied at 37 degrees C under two-electrode voltage-clamp conditions. Membrane depolarization beyond -40 mV from holding levels between -50 and -100 mV produced a delayed outward current which exhibited no inactivation within this voltage range. The current is carried primarily by K+ ions and its instantaneous I-V relation is linear. The total outward current could be separated into two distinct components on the basis of ion-substitution experiments. A voltage dependent component of the delayed current, termed IK(V), is activated by membrane depolarization beyond -40 mV when Ca2+ fluxes are selectively blocked by Cd2+ or in Ca2+-free solution. IK(V) develops following first-order kinetics and rises to a peak with a voltage-dependent delay (239 ms at -30 mV and 23 ms at +10 mV). GK(V) attains a saturating value of the order of 17 mS/cm2 at about +20 mV and can be described in terms of a simple Boltzmann distribution for a single gating particle with a valency equal to +2.5. A second component of the delayed outward current, termed IK(Ca), depends on Ca2+ entry for its activation and was isolated as difference current before and after block of Ca2+ movements across the membrane. IK(Ca) is larger and faster than IK(V): it is strictly related to Ca2+ influx and also depends on membrane potential depolarization. A distinct Ca2+ current, ICa, was recorded from the neurone exposed to Na+-free or tetrodotoxin solution. ICa was activated by membrane depolarization beyond -30 mV and reached a maximum value near 0 mV. Its activation agrees with fourth-order kinetics and becomes faster with increasing depolarization. The Ca2+ current developed with a voltage-dependent time to peak of 2.9-1.8 ms and thereafter completely inactivated. The relationship between ICa and IK(Ca) is discussed. The Ca2+-k+ repolarizing system is expected to be mainly associated with action potentials arising from a depolarized neurone, whereas the IA current (Belluzzi, Sacchi & Wanke, 1985) dominates the repolarization mechanism at the normal membrane potential. The effect of muscarine was examined. Muscarine (10-50 microM) produced a fall in conductance with a voltage dependence similar to that exhibited by GK(Ca) and was ineffective when removing extracellular Ca2+ or adding Cd2+. A partial suppression of ICa by muscarine is demonstrated. It is suggested that the decrease of the outward current magnitude in the presence of muscarine may be accounted for qualitatively by the reduction in ICa. PMID- 2580078 TI - A voltage-clamp analysis of membrane currents in solitary bipolar cells dissociated from Carassius auratus. AB - Membrane properties of solitary bipolar cells, mechanically dissociated from the enzyme-treated goldfish retina, were studied under current- and voltage-clamp conditions with 'giga-seal' suction pipettes (pipette solution 138 mM-K). The resting potential of solitary bipolar cells was about -30 mV. They responded to depolarizing current pulses with sustained depolarization, and to hyperpolarizing current pulses with an initial hyperpolarizing transient followed by a sag to a less hyperpolarized level. The current-voltage relationship determined under voltage-clamp conditions showed strong outward and inward rectification. The membrane currents consisted of four components; Ca current (ICa), voltage- and Ca dependent K currents (IK(V) and IK(Ca), respectively), and an inward current activated by membrane hyperpolarization (Ih). ICa was activated by membrane depolarization beyond -40 mV, was maximum at +10 mV and became smaller with further depolarization. No polarity reversal was seen. ICa was enhanced by equimolar replacement of Ca with Ba, and was blocked by 4 mM-Co. IK(Ca) was observed by membrane depolarization beyond -10 mV, was maximum at about +40 mV, and became smaller with further depolarization. This current was suppressed by 4 mM-Co, 1.6 mM-Ba, 35 mM-TEA or 30 microM-quinine. IK(V) was activated by membrane depolarization beyond -60 mV, and had slower kinetics that ICa or IK(Ca). The reversal potential of the tail current was close to the K equilibrium potential (EK), suggesting that this current is carried purely by K ions. IK(V) was inactivated slowly and nearly completely by sustained depolarization. IK(V) was blocked by 35 mM-TEA. Ih was activated by membrane hyperpolarization (less than 60 mV). The current showed a time-dependent increase. It was also dependent on the membrane potential, but not on the driving force of K ions. This current seems to be carried by a mixture of Na and K ions, since (1) in low Na solution, Ih became small in amplitude, and (2) the reversal potential of the tail current was between the Na equilibrium potential (ENa) and EK X Ih was blocked by 10 mM Cs, but was resistant to 0.2 mM-Ba. The resting potential and voltage responses of solitary bipolar cells are discussed in reference to the characteristics of each membrane conductance isolated in the present study. PMID- 2580079 TI - Permeability changes induced by L-glutamate in solitary retinal horizontal cells isolated from Carassius auratus. AB - Solitary horizontal cells isolated from goldfish retinae are depolarized by L glutamate (Glu) (Ishida, Kaneko & Tachibana, 1984), a possible candidate for the transmitter of photoreceptors. The underlying mechanisms were analysed under voltage-clamp conditions using 'giga-seal' suction pipettes in the whole-cell recording configuration. Glu induced an inward current at the resting membrane potential (ca. -57 mV). Membrane depolarization decreased the amplitude of Glu induced current and reversed its polarity to outward beyond approximately -3 mV. Membrane hyperpolarization below the resting potential decreased the amplitude of the Glu-induced inward current. When a K current through the anomalous rectifier, which is activated by membrane hyperpolarization (Tachibana, 1983), was blocked by Cs ions, this phenomenon disappeared and the Glu-induced current increased in amplitude with hyperpolarization. Mg ions had no effect on the reduction of the Glu-induced current at hyperpolarized potentials. It was strongly suggested that Glu produced two types of conductance change; a conductance increase due to an activation of Glu channels and a conductance decrease due to a blockage of the K current through the anomalous rectifier. The latter effect is analysed in detail in the following paper (Kaneko & Tachibana, 1985b). The Glu-activated channel was permeable to cations (Na, K, Ca, Mg, Tris and choline ions) with low selectivity, but not to anions. The least effective dose of Glu was less than 10 microM. The relation between the Glu-induced current and the membrane potential curved upwards near the reversal potential, and this relation was not affected by Mg ions. PMID- 2580080 TI - Effects of L-glutamate on the anomalous rectifier potassium current in horizontal cells of Carassius auratus retina. AB - The effects of externally applied L-glutamate (Glu) on K currents through the anomalous rectifier were studied in solitary horizontal cells dissociated from goldfish retinae under whole-cell voltage-clamp or cell-attached patch-clamp conditions using 'giga-seal' suction pipettes. In the whole-cell clamp experiments, hyperpolarization of the membrane below the resting potential (ca. 57 mV) induced a large voltage-dependent inward current which has been identified as the K current through the anomalous rectifier (Ianomal.). Application of Glu to the external medium reduced Ianomal.. Reduction of the inward current was not seen in preparations in which Ianomal. has been blocked by an application of Cs or Ba ions to the external medium. Single-channel currents through the anomalous rectifier were recorded under cell-attached patch-clamp conditions. The current showed an inward rectification; its amplitude increased with hyperpolarization of the patch membrane, and became below the noise level near the equilibrium potential of K ions (EK). No polarity reversal was observed even by a strong membrane depolarization. The patch membrane potential at which the current amplitude became undetectable shifted in parallel to the shift of EK. The open probability changed little with polarization of the patch membrane. When Glu (greater than 100 microM) was applied to the outside of the patch membrane, the number of available Ianomal. channels was decreased, but neither the single channel conductance, open or closed time constants, nor the open probability changed significantly. Removal of Glu produced the opposite sequence; i.e. the number of available Ianomal. channels increased with time. It was concluded that the reduction of the Glu-induced current at hyperpolarized potentials in the whole-cell recording configuration is due to the blocking action of Glu on Ianomal.. PMID- 2580082 TI - Currents carried by monovalent cations through calcium channels in mouse neoplastic B lymphocytes. AB - Membrane currents through the Ca2+ channel were studied in a hybridoma cell line (MAb-7B) constructed by fusion of S194 myeloma cells and splenic B lymphocytes from the mouse. The whole-cell variation of the patch-electrode voltage-clamp technique was used. When [Ca2+]o = 2.5 mM, [Na+]o = 150 mM and [Na+]i = 155 mM, the current reversed from inward to outward at 20.9 +/- 2.4 mV (mean +/- S.D., n = 62). Both inward and outward currents showed voltage-dependent inactivation with the same membrane potential dependence of steady-state inactivation. The decay time constant of the current decreased from about 27 ms at -44 mV to a saturation value of 16 ms at about -20 mV, and remained at this value even when the current became outward. From the above results both the inward and outward currents were considered to flow through Ca2+ channels. The inward current showed no change when the external Na+ was replaced with Cs+ or tetraethylammonium and increased when [Ca2+]o was increased. Also, the reversal potential became more positive with increasing [Ca2+]o with a slope of 29 mV/decade change of [Ca2+]o. Effects of different divalent cations examined at 10 mM concentration showed the reversal potential to become more positive in the order of Mn2+, Sr2+ approximately equal to Ba2+ and Ca2+ whereas the relative maximum amplitudes of peak inward current were 1.0 for Ca2+, 1.24 for Sr2+, 0.99 for Ba2+ and 0.07 for Mn2+. When [Ca2+]o or [Mg2+]o was reduced by chelators, monovalent cations became capable of carrying inward current through the Ca2+ channel. These monovalent currents share common kinetic properties with the Ca2+ current, as judged from the steady-state inactivation and the decay time constant of the current. The monovalent cation current was blocked by divalent cations in a voltage-dependent manner. The half-blocking concentrations of Ca2+ and Mg2+ at -45 mV were 2.0 X 10(-6) M and 3.0 X 10(-5) M respectively. The same voltage-dependent binding mechanism can explain the outward current carried by monovalent cations at large positive potentials at normal Ca2+ concentrations. The suppression of the monovalent currents by Ca2+ and Mg2+ showed different voltage dependences. The suppression by Ca2+ increased and then decreased as the membrane potential was made negative, whereas the suppression by Mg2+ increased monotonically. This difference can be explained by considering the fact the Ca2+ is permeant and Mg2+ is impermeant through the Ca2+ channel. PMID- 2580083 TI - Fertilization-induced ionic conductances in eggs of the frog, Rana pipiens. AB - Fertilization of the frog egg (Rana pipiens) elicits a positive-going shift in membrane potential (fertilization potential) that lasts 10-20 min and functions as a fast block to polyspermy. We examined the ion conductances underlying the fertilization potential, using the voltage-clamp technique. We measured the membrane capacitance during the fertilization potential by applying an alternating current. We also determined the intracellular K and Cl concentrations in the egg, using ion-selective micro-electrodes. The conductance is largest in the first 2 min after fertilization. Regardless of whether the stimulus is provided by one or by more than one sperm or by artificial activation, the size of the conductance increase is the same, reaching a maximum of about 40 microseconds. Two separate conductances are involved at fertilization: Cl and K. [K]i = 121 mM and [Cl]i = 44 mM. The natural external medium is pond water (approximated in our experiments by 10% Ringer solution); therefore, an increase in K and Cl conductances leads to an efflux of both ions. The equilibrium potential of the fertilization current is between the Cl and K equilibrium potentials (ECl and EK), closer to ECl. 10 mM-external tetraethylammonium (TEA) brings the equilibrium potential close to ECl and reduces the maximum conductance by about half. The Cl conductance is not blocked by 4-acetamido-4' isothiocyanostilbene-2,2'-disulphonic acid (SITS). The time courses of the K and Cl conductances are similar. The TEA-resistant conductance (primarily Cl conductance) activated at fertilization increases as the membrane potential becomes more positive. A voltage-sensitive Na conductance present in the unfertilized egg disappears after fertilization. During fertilization this conductance is too small to contribute significantly to the fertilization potential. The membrane capacitance increases by an average of 1.9 times in the first 2 min following the rise of the fertilization potential, during the period of cortical vesicle exocytosis. Capacitance then gradually decreases; at 1 h after fertilization, capacitance is 82% of the value in the unfertilized egg. The conductance increase precedes the capacitance increase by several seconds. Therefore the initial appearance of Cl and K channels cannot be accounted for by addition of membrane by cortical vesicle exocytosis. The conductance subsequently decreases, suggesting that the disappearance of the Cl and K channels is not caused by membrane removal. PMID- 2580081 TI - A voltage-gated potassium channel in human T lymphocytes. AB - Human peripheral T lymphocytes were studied at 20-24 degrees C using the gigaohm seal recording technique in whole-cell or outside-out patch conformations. The predominant ion channel present under the conditions employed was a voltage-gated K+ channel closely resembling delayed rectifier K+ channels of nerve and muscle. The maximum K+ conductance in ninety T lymphocytes ranged from 0.7 to 8.9 nS, with a mean of 4.2 nS. The estimated number of K+ channels per cell is 400, corresponding to a density of about three channels/micron2 apparent membrane area. The activation of K+ currents could be fitted by Hodgkin-Huxley type n4 kinetics. The K+ conductance in Ringer solution was half-maximal at -40 mV. The time constant of K+ current inactivation was practically independent of voltage except near the threshold for activating the K+ conductance. Recovery from inactivation was slow and followed complex kinetics. Steady-state inactivation was half-maximal at -70 mV, and was complete at positive potentials. Permeability ratios, relative to K+, determined from reversal potential measurements were: K+(1.0) greater than Rb+(0.77) greater than NH4+(0.10) greater than Cs+ (0.02) greater than Na+(less than 0.01). Currents through K+ channels display deviations from the independence principle. The limiting outward current increases when external K+ is increased, and Rb+ carries less inward current than expected from its relative permeability. Tail current kinetics were slowed about 2-fold by raising the external K+ concentration from 4.5 to 160 mM, and were 5 times slower in Rb+ Ringer solution than in K+ Ringer solution. Single K+ channel currents had two amplitudes corresponding to about 9 and 16 pS in Ringer solution. Replacing Ringer solution with isotonic K+ Ringer solution increased the unitary conductance and resulted in inward rectification of the unitary current-voltage relation. Comparable effects of external K+ were seen in the whole-cell conductance and instantaneous current-voltage relation. Several changes in the K+ conductance occurred during the first few minutes after achievement of the whole cell conformation. Most are explainable by dissipation of a 10-20 mV junction potential between pipette solution and the cytoplasm, and by the use of a holding potential more negative than the resting potential. However, inactivation of K+ currents became faster and more complete, changes not accounted for by these mechanisms. K+ efflux through open K+ channels in intact lymphocytes, calculated from measured properties of K+ channels, can account for efflux values reported in resting lymphocytes, and for the increase in K+ efflux upon mitogenic stimulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2580084 TI - Two components of muscarine-sensitive membrane current in rat sympathetic neurones. AB - Membrane currents induced by muscarine (Imus) were recorded in voltage-clamped neurones in isolated rat superior cervical ganglia. Two components of Imus were regularly recorded: an inward current resulting from inhibition of the outward K+ current, IM; and an outward current attributable to the reduction of a steady inward current. The presence of these two components caused a 'cross-over' in the current-voltage curves at -50 +/- 3 mV in neurones impaled with KCl-filled micro electrodes or at -63 +/- 4 mV in neurones impaled with K-acetate-filled electrodes. Both components of Imus were prevented by atropine. Both persisted in Krebs solution containing tetrodotoxin (1 microM), Cd2+ (200 microM) or 0 Ca2+. When IM was inhibited by external Ba2+ or internal Cs+ only the outward component of Imus could be detected. This component reversed at +3 +/- 2 mV in cells impaled with CsCl-filled electrodes or at -20 +/- 3 mV in cells impaled with Cs acetate-filled electrodes. The reversal potentials agreed with those for the currents induced by gamma-aminobutyric acid (+4 +/- 2 mV and -16 +/- 3 mV with CsCl and Cs acetate electrodes respectively). Replacement of external NaCl with Na acetate (so reducing external Cl- concentration ( [Cl-]o) from 155 to 22 mM) shifted the reversal potential for Imus by +25 and +14.5 mV in two cells impaled with CsCl-filled electrodes. A tenfold reduction of external [Na+] (by glucosamine replacement) did not significantly alter the reversal potential for Imus in KCl or CsCl-impaled cells. Under conditions where IM is already inhibited, the residual outward component of Imus can lead to hyperpolarization and inhibition of neuronal activity in unclamped cells. We conclude that both inward and outward components of Imus result from direct activation of muscarinic receptors on the ganglion cells. The inward component results from IM inhibition. We suggest that the outward component results from inhibition of another, voltage independent current IX which largely comprises a Cl- current. The inward component induces membrane depolarization and an increased excitability; the outward component can lead to hyperpolarization and reduced excitability. PMID- 2580085 TI - Effects of apamin, quinine and neuromuscular blockers on calcium-activated potassium channels in guinea-pig hepatocytes. AB - The bee venom peptide, apamin, has been radiolabelled with 125I, the monoiodinated derivative purified, and its binding to intact guinea-pig liver cells studied. At 37 degrees C 125I-monoiodoapamin associated with, and dissociated from, guinea-pig hepatocytes remarkably rapidly. The association and dissociation rate constants were 1.4 X 10(8) M-1 s-1 and 0.035 s-1 respectively. Equilibrium binding studies demonstrated a saturable binding component compatible with 1:1 binding to a single class of site and having an equilibrium dissociation constant (KL) of 390 pM. The maximal binding capacity was 1.1 fmol mg-1 dry wt. of tissue. Unlabelled apamin displaced bound 125I-monoiodoapamin with a KI of 380 pM, which is consistent with the concentration of apamin required to inhibit Ca2+ activated K+ permeability (PK(Ca) ) in these cells. Inhibitable binding of 125I monoiodoapamin to rat hepatocytes was much less than to guinea-pig hepatocytes and could not be reliably quantified. Neither was there any discernible inhibitable binding to human erythrocytes. This is in keeping with the reported lack of apamin-sensitive Ca2+-activated K+ channels in these cell types. Various agents were tested for their ability to inhibit monoiodoapamin binding to, and Ca2+-mediated K+ efflux from, guinea-pig hepatocytes. All compounds tested which inhibited binding also blocked K+ efflux at similar concentrations. TEA and quinine affected hepatocytes only at high concentration (KI = 5.8 and 0.51 mM respectively). 9-aminoacridine, quinacrine and chloroquine were slightly more effective (KI = 70-180 microM). By far the most active compounds (apart from apamin) were the neuromuscular blocking agents; tubocurarine, pancuronium and atracurium (KI = 7.5, 6.8 and 4.5 microM respectively). Gallamine was slightly less effective (KI = 14 microM) and decamethonium and hexamethonium much less so (KI = 620 and 760 microM respectively). 3,4-diaminopyridine, alpha-bungarotoxin and tetrodotoxin were among several compounds which showed little or no affinity for apamin binding sites or inhibition of K+ efflux in guinea-pig hepatocytes. The saturable binding of 125I-monoiodoapamin to guinea-pig hepatocytes corresponds to about 1700 sites per cell. Assuming, tentatively, that binding sites correspond to channels the rate of K+ loss observed following agonist action can readily be explained if these channels have unitary conductances in the range reported for PK(Ca) in other tissues. PMID- 2580086 TI - Apical membrane potassium and chloride permeabilities in surface cells of rabbit descending colon epithelium. AB - The apical membranes of surface cells in the rabbit descending colon possess a significant ionic conductance in parallel to amiloride-blockable Na+ channels. The identity of the ion(s) responsible for the amiloride-insensitive conductance is unknown. The purpose of the present paper was to assess the permeability and net driving forces for K+ and Cl- across this membrane using conventional and ion sensitive micro-electrode techniques. Intracellular Cl- activity (aiCl) averaged 23 +/- 2 mM with an equilibrium potential (ECl) of -38 +/- 2 mV. This value is less than previous estimates of the electromotive force (e.m.f.) of the amiloride insensitive pathway (ca. -50 mV). Consequently, Cl- alone cannot account for the amiloride-insensitive conductance. Replacement of Cl- by gluconate in the serosal solution decreased aiCl to 17 +/- 2.8 mM. aiCl was lowered to approximately 1 mM by replacement in the mucosal bath or by replacement in both solutions. The results indicate a low Cl- conductance in the basolateral membrane, in agreement with previous electrophysiological studies of this epithelium. In contrast to Cl , the chemical driving force for K+ was large enough to support the e.m.f. of the amiloride-insensitive pathway (K+ equilibrium potential, EK = -66 mV). The basolateral membrane potential (Vbl), EK and the intracellular K+ activity (aiK) were decreased in parallel following inhibition of the basolateral Na-K pump, providing evidence that Vbl is largely due to a K+ diffusion potential. In the presence of serosal 10(-4) M-ouabain, aiK appeared to remain above equilibrium and more than doubled after addition of Ba2+ to the serosal bath. Replacement of the mucosal bathing solution with KCl or gluconate Ringer solution largely restored Vbl and the transepithelial potential (VT) in tissues which had been previously treated with ouabain. The restoration of VT was decreased and the transepithelial resistance (RT) was increased by addition of tetraethylammonium to the mucosal bath. The above results suggest that there are at least four routes for ion movement across the apical membrane of rabbit colon surface epithelial cells. These are: (1) an amiloride-sensitive Na+ channel, (2) a K+ conductance, (3) electroneutral uptake of Cl- from lumen to cell interior and (4) an active K+ transport mechanism, also from lumen to cell interior. PMID- 2580087 TI - The ionic selectivity and calcium dependence of the light-sensitive pathway in toad rods. AB - A new method is described for determining the effects of rapid changes in ionic concentration on the light-sensitive currents of rod outer segments. Replacing Na with another monovalent cation caused a rapid change in current followed by an exponential decline of time constant 0.5-2 s. From the magnitude of the initial rapid change in current we conclude that Li, Na, and K and Rb ions pass readily through the light-sensitive channel in the presence of 1 mM-Ca, whereas Cs crosses with difficulty and choline, tetramethylammonium and tetraethylammonium not at all. The effect of reducing Ca in the external medium indicates that the residual inward current recorded for a few seconds when Na is replaced by an impermeant ion is carried largely by Ca ions. With 1 microM-Ca in the external medium the relative ability of monovalent cations to carry light-sensitive current is Li:Na:K:Rb:Cs = 1.4:1:0.8:0.6:0.15. The same order applied in the physiological region but the values are less certain. Large transient inward currents are seen if external Ca is raised form 1 microM to 5 mM or more; these currents which are maximal in an isotonic Ca solution are presumably carried by Ca. The effect of monovalent cations on the number of open light-sensitive channels was tested by adding the cation to a solution containing 55 mM-Na. Na ions open light-sensitive channels with a delay, probably by promoting Na-Ca exchange; K and Rb close channels by inhibiting exchange; Li and Cs seem inert in the exchange mechanism. The rate at which inward current declines in low [Na]o or high [Ca]o is accelerated by weak background lights and slowed by 3-isobutyl-1 methylxanthine (IBMX), which inhibits the hydrolysis of cGMP. On returning to Ringer solution after a period in low [Na]o the current recovers with a delay of about 1 s which decreases as the Ca concentration of the low [Na]o medium is reduced. We conclude that intracellular Ca has a strong effect on the number of open light-sensitive channels. None the less, several observations are inconsistent with channel closure being dependent simply on combination with internal Ca. PMID- 2580088 TI - Mechanism of action of insulin on acetylcholine-evoked amylase secretion in the mouse pancreas. AB - The effects of insulin and acetylcholine (ACh) on amylase secretion, transmembrane movement of 45Ca2+ and K+, membrane potential and cyclic nucleotide levels in the isolated mouse pancreas were investigated. Insulin alone had no effect on either amylase secretion or 45Ca2+ fractional efflux but it markedly potentiated the ACh-evoked amylase secretion and significantly reduced the ACh induced 45Ca2+ fractional efflux. These effects were dose related. Insulin evoked a small membrane hyperpolarization and an increase in K+ efflux. The islet hormone had virtually no effect on ACh-induced membrane depolarization but it markedly enhanced the ACh-elicited K+ efflux. Both insulin and ACh had marked time-dependent effects on the metabolism of adenosine 3',5'-cyclic monophosphate (cyclic AMP). Insulin increased and ACh decreased cyclic AMP concentration when applied separately. However, when added together, insulin and ACh caused a rapid and sustained elevation of cyclic AMP levels. Superfusion of mouse pancreatic fragments with an exogenous lipid-soluble derivative of cyclic AMP (dibutyryl adenosine 3',5'-cyclic monophosphate) caused dose-dependent increases in amylase secretion. Dibutyryl cyclic AMP also markedly enhanced, in a dose-dependent manner, the ACh-evoked amylase secretion. It is concluded that insulin may exert its potentiating action on ACh-evoked amylase output in the mouse pancreatic acinar cells by elevating both cytoplasmic Ca2+ and cyclic AMP levels. PMID- 2580089 TI - A fast transient outward current in the rat sympathetic neurone studied under voltage-clamp conditions. AB - Post-ganglionic neurones of the isolated rat superior cervical ganglion were voltage clamped at 37 degrees C using separate intracellular voltage and current micro-electrodes. Control experiments in current clamp suggested that the neurone is electrotonically compact, the soma and the proximal dendritic membranes being under good spatial voltage uniformity. Depolarizing voltage steps from membrane potentials near -50 mV evoked: (i) a voltage-dependent inward Na+ current, (ii) an inward Ca2+ current, (iii) a voltage-dependent outward K+ current, (iv) a Ca2+ activated K+ outward current. Depolarizations from holding potentials more negative than -60 mV elicited, besides the currents mentioned above, a fast transient outward current IA which peaked in 1-2.5 ms and then decayed to zero following an exponential time course. The IA current was shown to be primarily, if not exclusively, carried by K+. It was unaffected by removal of external Ca2+ or addition of Cd2+ and was weakly blocked by tetraethylammonium ions and partially by 4-aminopyridine. The IA current showed a linear instantaneous current-voltage relationship. Its activation ranged from -60 to 0 mV with a mid point at -30 mV. The A conductance could be described in terms of a simple Boltzmann distribution for a single gating particle with a valency of +3. Both the development and removal of inactivation followed a single exponential time course with a voltage-dependent time constant which was large near the resting potential (42 ms at -70 mV) and small (11 ms) near -100 and -40 mV. Steady-state inactivation h infinity ranged from -100 to -50 mV, with a mid-point at -78 mV, suggesting that approximately 50% of the IA channels are available at the physiological resting potential. Action potentials elicited from various holding potentials showed maximal repolarization rates dependent on the holding potential itself. This voltage dependence was found to be in reasonably good agreement with that of h infinity curve. These data are consistent with the view that in the rat sympathetic neurone, under physiological conditions, it is the IA current rather than the delayed outward current that is responsible for the fast action potential repolarization. PMID- 2580090 TI - Behind the walls of aphasia. PMID- 2580091 TI - Immune complex activation of neutrophils and enhancement of the activation by rheumatoid factor and complement. AB - The activation of human neutrophils by heat aggregated human immunoglobulin and preformed immune complexes was studied using a chemiluminescent technique. Insoluble aggregates of large size and complexes with antigen/antibody ratios at equivalence produced maximal activation. All responses were enhanced by preincubation with fresh serum. Preincubation of neutrophils with zymosan activated serum also enhanced neutrophil responses. Rheumatoid factor modulated the interaction and in excess reduced all responses, while at optimum concentration caused enhancement. These activation processes result in the release of reactive oxygen metabolites which are considered important inflammatory mediators in the pathogenesis of rheumatoid arthritis. PMID- 2580092 TI - Significance of antikeratin antibodies in rheumatoid arthritis. AB - Antikeratin antibodies (AKA) were found in the sera of 59% (121/204) of patients with rheumatoid arthritis (RA). There was a significantly higher incidence of AKA (73%) in male patients compared with females (53%) and a correlation between AKA positivity and IgM rheumatoid factor was found. Antibody reactivity was positively associated with the presence of nodules, antinuclear antibody, C reactive protein and disease severity. AKA would appear to have possible prognostic significance in patients with RA. PMID- 2580093 TI - Plasma beta-thromboglobulin in the differential diagnosis of Raynaud's phenomenon. AB - Plasma beta-thromboglobulin (beta TG) levels were measured by radioimmunoassay in 61 patients with systemic sclerosis, 19 with carefully defined primary Raynaud's phenomenon, and 8 with Raynaud's phenomenon in suspected transition to systemic sclerosis. Elevated beta TG was present in 50 (82%) patients with systemic sclerosis but levels could not be correlated with duration or extent of disease nor any particular pattern of visceral involvement. Transitional Raynaud's patients had elevated beta TG in 7 (88%) cases, whereas results in patients with primary Raynaud's phenomenon were comparable to normal controls. beta TG, a sensitive measure of in vivo platelet activation, is useful in the differential diagnosis of Raynaud's phenomenon. PMID- 2580094 TI - Alcohol-induced urticaria. PMID- 2580096 TI - The expression of Leu M4 on human NK cells. AB - Previous studies have shown that the Leu M4 monoclonal antibody reacts strongly with human granulocytes in the peripheral blood, has a weak reactivity with monocytes but fails to react with platelets, eosinophils and K-562 cells. In the present study Leu M4 antibody was found to react with human NK cells. Immunofluorescent analysis indicated that about 12% of peripheral blood lymphocytes (PBL) are positive for this marker, and that the reactive cells are concentrated in the Percoll fraction known to display the strongest NK activity. Exposure of PBL to Leu M4 and complement resulted in a significant decrease of their NK activity. The relationship of Leu M4 to other monoclonal antibodies reactive with human neutrophils and NK cells remains to be elucidated. PMID- 2580095 TI - beta (+)-Thalassaemia in the Po river delta region (northern Italy): genotype and beta globin synthesis. AB - Six beta(+)-thalassaemic patients from the Po river delta region have been studied. Using synthetic oligonucleotides as specific hybridisation probes, the beta(+) IVS I mutation (G----A at position 108) was demonstrated. This lesion and the enzyme polymorphism pattern in the subjects examined are the same as have been described for other Mediterranean beta(+)-thalassaemias. Antenatal diagnosis through DNA analysis of beta(+)-thalassaemia is therefore possible. The production of beta globin in a beta(+), homozygote and in a beta (+), beta(0) 39 (nonsense mutation at codon 39) double heterozygote is approximately 20% and 10% respectively of total non-alpha globin synthesis. Despite some overlapping of the results, similar beta globin synthesis levels have been obtained in 43 beta(+) thalassaemia patients. This suggests that in the Po river delta region the most common thalassaemic genes are beta(0) 39 and beta(+) IVS I. PMID- 2580097 TI - Directly photocrosslinked nucleotides joining transfer RNA to aminoacyl-tRNA synthetase in methionine and tyrosine systems. AB - We have used ultraviolet photocrosslinking and 32P post-labeling to help define the contact surface between transfer RNAs and aminoacyl-tRNA synthetases for the methionine and tyrosine systems. Photocrosslinking between tRNAs and synthetases is shown to occur only in cognate complexes. The increased sensitivity of our procedures reduces the amounts of interacting macromolecules and permits lower ultraviolet light doses, thereby minimizing radiation damage. These procedures have detected crosslinks only within the 3'-terminal RNase T1 fragments in yeast tRNAMeti and Escherichia coli tRNATyr2; and although the photoadducts were unstable, we have identified the crosslinked nucleotides. These crosslinks occur at positions C74 and A76 in yeast tRNAMeti and position U64 in E. coli tRNATyr1&2 (conventional tRNA numbering system of Gauss & Sprinzl, 1981). This work demonstrates that even labile photocrosslinks can be exploited for mapping crosslinked nucleotides. PMID- 2580098 TI - Structure and genomic organization of the rat aldolase B gene. AB - The structure of the chromosomal gene encoding rat aldolase isozyme B has been elucidated by sequence analysis of cloned genomic DNA. This gene comprises about 14 X 10(3) base-pairs of DNA, and is separated into nine exons by eight intervening sequences. A presumed transcription-initiation site was assigned by S1 nuclease protection mapping, and T-A-T-A and C-C-A-A-T boxes were found to be 25 and 126 base-pairs, respectively, upstream from this initiation site. There are three characteristic sequences of 100 to 200 base-pairs within the region of 870 base-pairs flanking the 5' side of the gene. These sequences are flanked on either side by direct repeats and terminate with an A-rich stretch of nucleotides. One of them has block homology with a region in an "ID sequence", which is reported to be an element for tissue-specific gene regulation and differentiation. The other two are analogous at the sequence organizational level with a sort of dispersed repeat, the "Alu family". These features suggest that these regions are involved in gene regulation and, also, imply evolutionary events such as duplication or insertion. Comparison of this gene sequence with the rabbit aldolase A complementary DNA sequence revealed some bias in the frequency of nucleotide replacement among the exons, suggesting selective evolutionary conservation of particular exons encoding functional domains. Comparison with the human aldolase B complementary DNA sequence revealed no such tendency; the homology between the two sequences was very high (about 89%), and nucleotide replacements were randomly distributed throughout the protein-coding region. PMID- 2580099 TI - Transcription of the replication control region of the IncFII R-plasmid NR1 in vitro and in vivo. AB - The minimal replicon of the 90,000 base-pair IncFII R plasmid NR1 consists of a 2700 base-pair region of the DNA. Minireplicator plasmids consisting of the 2700 base-pair minimal replicon plus a 2200 base-pair region coding for chloramphenicol acetyltransferase (cat) were used as templates for in vitro transcription. Six RNA transcripts were synthesized from these templates in vitro. We have determined the directions of transcription and the approximate sites of initiation and termination of each of the in vitro RNA transcripts. One RNA transcript was synthesized from the cat gene, while the other five were transcribed from the minimal replicon. Four of the RNA transcripts also were identified by quantitative hybridization of RNA synthesized in vivo from these minireplicator plasmids. The strengths of the promoters for the RNA transcripts were estimated by the relative rates of transcription both in vitro and in vivo. Transcription from convergent promoters reduced the rate of RNA synthesis in vivo in both directions. In vivo, a significant fraction of the cat mRNA was extended past its in vitro termination point. Transcription of mutants that have altered plasmid copy number and/or incompatibility properties also were examined. The possible roles of each of the transcripts as mRNA and their involvement in regulation of DNA replication are discussed. PMID- 2580100 TI - Recombinant DNA approach for defining the primary structure of monoclonal antibody epitopes. The analysis of a conformation-specific antibody to myosin light chain 2. AB - A monoclonal antibody (MF5), capable of recognizing a divalent cation-induced conformational change in myosin light chain 2 (LC2f), has been used to screen a cDNA library constructed in the expression vector lambda gt11. A clone has been isolated that contains the whole coding sequence of this myosin subunit. The light chain was synthesized as a fusion peptide linked to beta-galactosidase by ten amino acids encoded in the 5' untranslated region of its mRNA. Seven imperfect repeats were identified in the 3' untranslated region of the mRNA. The amino acids conferring specificity on the MF 5 epitope were established by first determining the nucleotide sequence of shorter subclones that expressed the epitope and then eliminating those amino acid residues shared by cardiac myosin LC2, which was unreactive with this antibody. The epitope, which becomes accessible to MF 5 upon removal of bound divalent cations, resides at the junction between the first alpha-helical domain and the metal binding site. Theoretically, this approach can be used to define the primary structure of most protein epitopes. PMID- 2580102 TI - Ophthalmic surgical assisting requires teamwork! PMID- 2580101 TI - Protein normal-mode dynamics: trypsin inhibitor, crambin, ribonuclease and lysozyme. AB - We have developed a new method for modelling protein dynamics using normal-mode analysis in internal co-ordinates. This method, normal-mode dynamics, is particularly well suited for modelling collective motion, makes possible direct visualization of biologically interesting modes, and is complementary to the more time-consuming simulation of molecular dynamics trajectories. The essential assumption and limitation of normal-mode analysis is that the molecular potential energy varies quadratically. Our study starts with energy minimization of the X ray co-ordinates with respect to the single-bond torsion angles. The main technical task is the calculation of second derivative matrices of kinetic and potential energy with respect to the torsion angle co-ordinates. These enter into a generalized eigenvalue problem, and the final eigenvalues and eigenvectors provide a complete description of the motion in the basic 0.1 to 10 picosecond range. Thermodynamic averages of amplitudes, fluctuations and correlations can be calculated efficiently using analytical formulae. The general method presented here is applied to four proteins, trypsin inhibitor, crambin, ribonuclease and lysozyme. When the resulting atomic motion is visualized by computer graphics, it is clear that the motion of each protein is collective with all atoms participating in each mode. The slow modes, with frequencies of below 10 cm-1 (a period of 3 ps), are the most interesting in that the motion in these modes is segmental. The root-mean-square atomic fluctuations, which are dominated by a few slow modes, agree well with experimental temperature factors (B values). The normal-mode dynamics of these four proteins have many features in common, although in the larger molecules, lysozyme and ribonuclease, there is low frequency domain motion about the active site. PMID- 2580103 TI - Evoked response studies in detrusor hyperreflexia due to infravesical obstruction in neurological patients. AB - Urodynamic evaluation was performed on 80 patients with urological disorders identified as benign prostatic hypertrophy whose main complaints ranged from irritation to urine loss owing to urgency. Detrusor hyperreflexia was detected in 40 patients, of whom 24 were operated on either by the transurethral or the retropubic approach. At repeat urodynamic evaluation about 1 year postoperatively function had returned to normal in 14 patients and the hyperreflexia persisted in 10. The preoperative evoked response in these latter 10 patients was less than 60 msec. It is possible that apart from the diagnosis of detrusor hyperreflexia by cystometric examination in patients with benign prostatic hypertrophy an abbreviated evoked response could indicate deterioration in neural function with or without an accompanying neurological disease. If this is the cause of detrusor hyperreflexia then prostatectomy will not ameliorate the condition but can only subject the patient to the risk of urine loss. PMID- 2580104 TI - Transient blindness following transurethral resection of the prostate in an achondroplastic dwarf. AB - Neurological complications associated with transurethral resection of the prostate have been reported in the past. We report on an achondroplastic dwarf who suffered transient blindness following transurethral resection of the prostate. The blindness correlated with a markedly elevated serum glycine level of 13,734 mumol. per l. We discuss the possibility of glycine being responsible for this complication. PMID- 2580105 TI - Evidence for the association between blood prolactin and androgen receptors in BPH. AB - The purpose of this study was to investigate the relationship between prostatic androgen receptors and plasma prolactin and testosterone in patients with benign prostatic hyperplasia. Cytosolic and KCl extractable nuclear androgen receptors were measured in 22 patients and these were in turn correlated to the hormone concentrations in blood specimens taken on the morning before the day of operation. The mean +/- S.E.M. concentrations of cytoplasmic androgen receptors, KCl extractable nuclear androgen receptors, plasma testosterone and plasma prolactin were respectively 115 +/- 18 fmoles/gm. tissue, 198 +/- 40 fmoles/gm. tissue, 15.6 +/- 1.2 nmol./l. and 128 +/- 17 mU/l. Plasma prolactin was highly correlated with cytosolic androgen receptors (r = 0.784, p less than 0.01; no. = 15) though not with nuclear androgen receptors (r = 0.453, p greater than 0.05; no. = 15). However, when the androgen receptor levels were expressed as fmoles/mg. protein both cytosolic and nuclear levels were proportional to plasma prolactin (p less than 0.01 and p less than 0.02 for both the cytosolic and nuclear receptors respectively; no. = 15). There was no correlation between either cytosolic and nuclear androgen receptors and plasma testosterone levels. The results suggest that plasma prolactin may be involved in the regulation of androgen receptor content in the benign prostate. PMID- 2580106 TI - Results and benefits of a maternal serum alpha-fetoprotein screening program. PMID- 2580108 TI - [Binding of peanut agglutinin (PNA) and Dolichos biflorus agglutinin (DBA) to human colonic carcinomas, adenomas, and polyps: histochemical staining by the lectin-antilectin-PEP method]. AB - Binding of 2 lectins--peanut agglutinin (PNA) and Dolichos biflorus agglutinin (DBA)--with human colonic carcinomas, adenomas, juvenile and hyperplastic polyps, and polyps in Cronkhite-Canada syndrome was examined histochemically by the lectin-antilectin-PAP method. With PNA, brush borders of the carcinoma cell were stained(90.9%), while the cytoplasm of the adenomas and polyps were stained granularly (88.0%). With DBA, the cytoplasm of the carcinomas was stained diffusely (72.7%), though 25% of the cases showed the fringed type cytoplasmic staining similar to adenomas, polyps and normal crypts. It appears important to recognize the differences in the staining patterns, especially in PNA, between carcinomas and other benign lesions, which apparently reflect changes of sugar residues during cancerization. PMID- 2580107 TI - Evaluation of antiarrhythmic drug efficacy using holter electrocardiographic technique. AB - This study was performed to investigate spontaneous variability in VPC frequency, to determine standards for distinguishing antiarrhythmic efficacy from the spontaneous variability, and to compare the effectiveness of disopyramide, mexiletine, aprindine, propranolol, and diltiazem. Holter ECG techniques were used for this study and the population studied consisted of 182 patients having more than 1000 VPCs/day. Forty patients had ischemic heart disease, 52 had miscellaneous heart disease and 90 were free of heart disease (idiopathic VPCs). Circadian variability of VPCs can be divided into 4 types; Type D (VPCs increasing during waking hours), Type DN (small VPC changes between waking and sleeping hours), Type N (VPCs increasing during sleeping hours) and Type Ir (irregularly occurring VPCs). The incidence of Type D, DN, N and Ir was 45%, 29%, 12% and 14%, respectively. VPC frequency in the first and second recordings at a 7 up to 21 day interval was highly reproducible (r = 0.951). The percent reduction in VPC frequency necessary to distinguish true drug response from spontaneous VPC variability, corresponded to 57% with 95% confidence level, and 67% with 99% confidence level. VPCs were reduced by at least 57% in 19 out of 33 patients (58%) with disopyramide, 9 of 15 (60%) with mexiletine, 11 of 18 (61%) with aprindine, 9 of 24 (38%) with propranolol and 8 of 22 (36%) with diltiazem. Concerning Prop., it is exclusively effective to the Type D VPCs (70%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580109 TI - Angioarchitecture of thyroid carcinoma. AB - Since thyroid carcinoma is a tumor originating in an organ with a rich vascular supply, its biological characteristics seem to depend upon tumor vessels. From this point of view, we performed thyroid angiography clinically and examined the structure of the vessel wall histologically. The thyroid angiography demonstrated abnormal neoplastic vascularization, tumor stains and the presence of an arterio venous fistula within the tumor. According to the pharmaco-thyroid angiography, the vessels in the cancerous tissue, unlike normal vessels, lacked a humoral response. Histochemical fluorescence study revealed no specific fluorescence indicative of the presence of catecholamines in tumor vessels, suggesting that the vessel is embryonic in character. The angioarchitectonic picture of the tumor vessels was polymorphous consisting chiefly of a tree-shaped ramification type and a peculiar saccular or fusiform dilatation type. The punctate or linear type seen in the normal tissue was only a minor component. PMID- 2580110 TI - Nasopharyngeal carcinoma: immunohistochemical study for keratin, secretory component and leukocyte common antigen. AB - Immunohistochemical studies using antisera to keratin and secretory component (SC) and monoclonal antibody against leukocyte common antigen (LCA) were performed on 92 biopsy and autopsy specimens taken from 65 patients with nasopharyngeal carcinoma. Five biopsy specimens from malignant lymphoma of the nasopharynx and tonsil, and 20 biopsy specimens of nasopharyngeal epithelium were also included in the study. Keratin was positively stained in all squamous cell carcinomas and nonkeratinizing carcinomas, and 38 of 46 undifferentiated carcinomas (82.6%), but in no malignant lymphomas. LCA was intensely stained in all malignant lymphoma, but in no nasopharyngeal carcinomas. SC was positively stained in two of the 46 undifferentiated carcinomas (4.3%). Nasopharyngeal carcinoma is a definite malignant epithelial neoplasm and can be distinguished from malignant lymphoma by immunostaining for keratin and LCA. Some undifferentiated carcinoma may show cellular differentiation toward ciliated epithelium. PMID- 2580111 TI - [Surgical nursing (9). Recovery room nursing: respiratory care (4)]. PMID- 2580112 TI - [Nursing technology: surgical nursing (10). Recovery room nursing: respiratory care (5)]. PMID- 2580113 TI - [Improvement of health care of infants and young children: follow-up of cases referred by child care centers]. PMID- 2580114 TI - [Late failure of porcine pericardial monocusp in palliative right ventricular outflow tract reconstruction for tetralogy of Fallot]. PMID- 2580115 TI - [Cluster analysis of 109 patients with systemic lupus erythematosus]. AB - Using a grouping method we studied the disease homogeneity within a group of 109 patients with systemic lupus erythematosus. The mean observation period was 6 years and 8 months. By using a cluster analysis, the total group of patients could be subdivided into two subgroups which differed clearly in their symptomatology. One subgroup (n = 42) showed higher incidence of elevated serum creatinine values, proteinuria, oral ulceration and severe anaemia. All 13 deaths occurred in this group. The second group (n = 67) was characterized by a more benign course of disease, a notably decreased incidence of renal involvement, and the Raynaud's Phenomenon was comparatively frequent. PMID- 2580116 TI - [Immunologic and electron microscopic findings in an unusual case of Whipple's disease]. AB - Whipple's disease is a curious disorder with the involvement of many organ systems, primarily gut, synovium and the central nervous system, characterized by the presence of numerous proliferating bacteria in tissue macrophages and other cell types. While clinically this disease entity has previously been defined by the classical triad of diarrhoea, malabsorption and weight loss, some patients do not show these features. In this report, a clinically unusual case of Whipple's disease is described presenting with high persistent fever, severe arthralgias and headaches, but without malabsorption, diarrhoea or weight loss. Nevertheless, the histological and electron microscopical pictures demonstrated the typical findings of intracellular micro-organisms along with the presence of bacteria in Schwann nerve cells, which has only once been described previously. Immunological findings before treatment demonstrated a decrease of T cells with the helper/inducer phenotype, and a concomitant rise in cells with the suppressor/cytotoxic phenotype, an elevation of "activated" Ia positive T cells and a significant reduction of T cell mitogenic responsiveness. Of special interest, after a successful treatment these immunological abnormalities shifted to normal with the exception of a still elevated number of Ia+ T cells. The discussion of this unusual case of Whipple's disease includes - besides possible cellular immunological abnormalities - genetic factors, especially since this patient was HLA-B-27-positive as was his son who is suffering from ankylosing spondylitis. PMID- 2580117 TI - Immunogenetic aspects of a canine breeding colony. AB - A colony of dogs was expanded by selective breeding to study the immunogenetic determinants coded for by the major histocompatibility complex (DLA). Polymorphic determinants were identified by alloantisera specific for DLA-A and B loci antigens and by the mixed lymphocyte culture (MLC) which defined alleles at the D locus. Thirteen families totaling 58 offspring were produced and typed for allelic determinants coded for by each of the three gene loci. Allelic segregation in a codominant manner occurred as expected and a recombinant between the A and B loci was detected. A number of animals were homozygous at one or more loci, thus providing genetically standardized animals as a source of typing cells, antigens, and sera to further study the immunogenetic details of DLA and for in vivo studies in transplantation biology. PMID- 2580118 TI - Neuroendocrine (Merkel) cells of the skin: hyperplasias, dysplasias, and neoplasms. PMID- 2580119 TI - Glomerular hyalinosis and its relation to hyperfiltration. AB - Reduction in renal mass in rats results in hyperfiltration of the remnant nephrons, accompanied by injury to the glomeruli and their eventual sclerosis. This study was undertaken in a rat model with 5/6 reduction of renal mass to follow the evolution of glomerular damage, over an 11-week period, with particular emphasis on the widely prevalent, although seldom discussed, lesion of hyalinosis. Light, electron, and immunofluorescence microscopic studies were performed and blood pressure, excretion of urinary albumin, and serum creatinine levels determined. Systolic blood pressure, urinary albumin excretion, and serum creatinine levels were all increased by the third week following operation. Blood pressure and serum creatinine continued to increase throughout the period of study. Glomerular damage was focal and segmental, and glomeruli were equally affected in both the juxtamedullary and outer zones of the cortex. Endothelial injury was noted to be the first indicator of glomerular damage, followed closely by alterations in the epithelial cells. The early hyalinosis lesion was characterized by an accumulation of homogeneous electron-dense material beneath damaged endothelial cells with later encroachment on the capillary lumen resulting in the easily recognizable eosinophilic, periodic acid-Schiff-positive lesion by light microscopy. These alterations were accompanied by complex changes within the mesangium, including both mesangiosclerosis and mesangiolysis. Glomerular hyalinosis, glomerular sclerosis, vascular damage, blood pressure, and albuminuria were ranked in order of severity and the rankings subjected to multiple regression analysis. Significant correlations were present between glomerular sclerosis and hyalinosis, arterial damage and blood pressure, and hyalinosis and urinary albumin excretion. The hyalinosis lesion accompanying the progressive glomerular sclerosis in this model resembles that seen in a number of human conditions. In addition, the correlations of hyalinosis with glomerular sclerosis and albuminuria reflect its association with glomerular injury; it is likely that it will prove to be a reliable marker of hyperfiltration injury. PMID- 2580120 TI - Ultrastructural distribution of fibronectin in normal and fibrotic human lung. AB - We studied the distribution of fibronectin in normal and fibrotic adult human lung and normal hamster lung using affinity-purified antifibronectin Fab' horseradish peroxidase conjugates. In normal lung, fibronectin staining was present in alveolar capillary and epithelial basal lamina and associated with interstitial collagen fibers. In airway and larger vessels, fibronectin staining was associated with the basal lamina of smooth muscles. In contrast to the relative paucity of staining in normal lung, the alveolar basal lamina of fibrotic lung stained intensely for fibronectin. In addition, there was strong, periodic (approximately 600 A) staining of native collagen fibers for fibronectin. We conclude that fibronectin antigenicity is present in the alveolar epithelial and capillary endothelial basal lamina of normal human and hamster lung. The marked alterations in the apparent amounts and distribution of fibronectin in fibrotic human lung suggest its involvement in the cellular events accompanying human lung fibrosis. PMID- 2580122 TI - Written narratives of deaf and hearing students: story recall and inference. AB - The ability of deaf high school students to recall propositions and inferences from prose was examined and compared with that of hearing students. Students were asked to read and then write a given story. The hearing students recalled significantly larger numbers of propositions than deaf students, but both deaf and hearing students recalled similar numbers of story inferences in their written narratives. The interaction between the deaf students' reading comprehension levels and their narratives revealed that better readers were more accurate in recalling explicit propositional information but were not different in recalling implicit content. Theoretical and clinical implications are discussed. PMID- 2580121 TI - Varying expression of cytokeratin and neurofilaments in neuroendocrine tumors of human gastrointestinal tract. AB - Twelve cases of gastrointestinal neuroendocrine tumors, including eight carcinoids and four pancreatic islet cell tumors or their metastases, were immunohistochemically analyzed for the expression of different types of intermediate filament proteins. All of the tumors showed cytokeratin positivity in immunostaining, and the Western blotting technique revealed 45- and 52 kilodalton cytokeratins in carcinoid tumors. Three of the islet cell tumors, but none of the carcinoid tumors, showed, in addition, varying numbers of neurofilament-positive tumor cells when evaluated with rabbit and mouse monoclonal antineurofilament antibodies. The presence of only the 70-kilodalton neurofilament and cytokeratin polypeptides in an islet cell tumor was revealed also by using the Western blotting technique. On the other hand, both fetal and adult pancreatic islet cells showed only cytokeratin positivity. Neurofilament positive epithelial cells were not found in normal small intestines either. The results show epithelial characteristics in normal gastrointestinal neuroendocrine cells and neuroendocrine tumors by their expression of cytokeratin. In addition, some islet cell tumors display the 70-kilodalton neurofilament protein which suggests the acquisition of a new type of intermediate filament during the neoplastic change. PMID- 2580123 TI - Islet cell isolation in experimental d,l-ethionine pancreatitis in dogs. AB - Bulk isolation of islets of Langerhans for biochemical studies or transplantation has generally been associated with significant or even prohibitive contamination by acinar tissue. High-purity islet preparations are associated with an extremely low yield. The acinar tissue can be ablated with d,l-ethionine, but previously, this tactic has been restricted to rodents because of toxicity problems in larger animals. A dosage regimen in dogs which reduces amylase content of the pancreas to 0.3% of normal with complete preservation of insulin content is reported. Ductal perfusion with collagenase permits the recovery of 45% of the islet cell mass as determined by extractable insulin. These islets prove functional in in vitro perifusion studies and in allografts. PMID- 2580124 TI - The developmental screening and referral practices of physicians in Tennessee. PMID- 2580125 TI - An analysis of the decrease in the assayed level of charged bovine estrogen receptor observed at physiological ionic strength. AB - Lower assayed levels of heifer uterine estrogen receptor (ER) occur at physiologic ionic strength when ER is separated from [3H]estradiol by Dextran coated charcoal treatments, or by gel filtration on Sephadex or polyacrylamide resins. The assayed level of charged ER in buffers containing 150-200 mM ionic strength is approximately one-half that of ER levels assayed in buffers either at 0-50 or 400-450 mM ionic strength. Treatment of ER with trypsin or molybdate eliminates this observed reduction. Evidence is presented that the decrease results from a preferential adsorption of ER to the assay resins at 150-200 mM ionic strength. This adsorption is likely to be mediated by a hydrophobic region of the ER, which is removed by trypsin cleavage. PMID- 2580126 TI - Vasopressin and renin in high output heart failure of rats: hemodynamic effects of elevated plasma hormone levels. AB - We studied the hemodynamic effects of vasopressin and the renin-angiotensin system in an animal model of high output heart failure in conscious rats (aorto caval fistula). We found significantly elevated levels of plasma renin concentration (p less than 0.025), norepinephrine (p less than 0.02), and up to 4 to 5 times higher values of vasopressin (p less than 0.002) in the rats with heart failure as compared with control animals. In contrast to the control rats that had a normally functioning osmoreceptor system, we found an inverse relationship between plasma osmolality and arginine vasopressin in the rats with heart failure in association with edema. Using a specific antagonist of the pressor activity of vasopressin, we found no significant effect on heart rate, mean arterial pressure, cardiac output (thermodilution), and peripheral vascular resistance in the control animals and in the rats with aorto-caval fistula. Captopril resulted in a significant fall of mean arterial pressure in the rats with shunt (p less than 0.001). The coincidence of high values of vasopressin and, in a number of animals, low plasma osmolalities and edema suggests a role of vasopressin in the formation of edema and in the development of "dilutional hypo osmolality." PMID- 2580127 TI - Effect of SA-446, an angiotensin-converting enzyme inhibitor, on renal function in anesthetized dogs: special reference to arachidonic acid metabolites. AB - Intravenous infusion of SA-446 (1 mg/min) decreased systemic blood pressure and increased renal blood flow in anesthetized dogs. These changes were accompanied by a slight natriuretic response. During the infusion of this dose of SA-446, the pressor response to angiotensin I was abolished and the depressor response to bradykinin was markedly potentiated. Administration of indomethacin (13 mg/kg i.v.) suppressed natriuresis and, to some extent, the renal vasodilation caused by SA-446. Before and after administration of SA-446, four arachidonate metabolites, prostaglandin E2, prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2, were determined in plasma and urine by radioimmunoassay. There were no remarkable changes in levels of prostaglandins and thromboxane B2 in arterial and renal venous plasma. The urinary excretion of the metabolites varied little, but thromboxane B2 excretion did significantly decrease. Thus, reduction in the biosynthesis of thromboxane B2 in the kidney may relate to the effects of SA-446 on renal hemodynamics and urine formation. PMID- 2580128 TI - Disopyramide-pyridostigmine: report of a beneficial drug interaction. AB - A previously unrecognized beneficial drug interaction is described. Without affecting the antiarrhythmic properties of disopyramide, a sustained-release form of pyridostigmine (a cholinesterase inhibitor) was shown to prevent completely anticholinergic side effects in a study population (17 patients), whereas side effects occurred in 26 of 89 patients (29%) in a control group (p less than 0.025). Pyridostigmine also diminished or abolished disopyramide-induced anticholinergic side effects in each of 10 patients in whom they were already present. Pyridostigmine allowed an increase in tolerated disopyramide blood levels (4.53 +/- 1.59 micrograms/ml versus 3.85 +/- 1.78 micrograms/ml) and a significant increase in disopyramide dosages (224 +/- 68 mg versus 188 +/- 68 mg every 6 h) (p less than 0.02). No patients suffered side effects from pyridostigmine. These data suggest that pyridostigmine can be used to prevent as well as to treat the anticholinergic side effects of disopyramide. The usefulness of disopyramide has previously been limited by these anticholinergic side effects. Further investigation is in progress to determine what role pyridostigmine can play in making disopyramide therapy available to patients who otherwise could not benefit from its use. PMID- 2580130 TI - Antihypertensive and metabolic effects of long-term therapy with nifedipine slow release tablets. AB - Sixteen nonhospitalized men, average age 41.3 years with essential hypertension (WHO I-II) were given nifedipine slow-release tablets of 20 mg twice daily for 48 weeks. Both supine and standing blood pressure values were significantly reduced, but heart rate was not significantly changed by the drug. A significant decrease in serum sodium and potassium was found. A slight increase in serum magnesium throughout the study became statistically significant at 48 weeks (p less than 0.05). It is suggested that a possible diuretic activity, and the increase in magnesium, may add to the direct nifedipine-induced blood pressure reduction. Serum creatinine increased significantly after 24 and 48 weeks of nifedipine administration; serum urea, cholesterol, triglycerides, uric acid, and blood glucose remained essentially unchanged. Most of the patients had low plasma renin activity (PRA) in the control period, and nifedipine significantly increased PRA. Body weight was kept constant. Side effects were few and of no clinical significance. The slow-release preparation of nifedipine seems to be a potent and effective drug in treating essential hypertension of a mild to moderate degree. PMID- 2580129 TI - Protective effects of trans-13-APT, a thromboxane receptor antagonist, in endotoxemia. AB - The effect of the thromboxane A2/prostaglandin H2 (TxA2/PGH2) receptor antagonist trans-7[2-(p-hydroxyphenethylamino)-cyclopentyl]-heptanoic acid (trans-13-APT) on certain pathogenic sequelae of endotoxic shock and associated changes in arachidonic acid metabolism in the rat was investigated. trans-13-APT, an analog of 13-azaprostanoic acid, was synthesized and found to block human platelet aggregation induced by the thromboxane mimetic U46619. Pretreatment with trans-13 APT did not significantly alter the elevations in plasma immunoreactive (i) TxB2 or iPGE, 0.5 or 4 h after the intravenous administration of Salmonella enteritidis endotoxin. However, in the trans-13-APT-pretreated group, 4 h after administration of the endotoxin, plasma i6-keto-PGF1 alpha was significantly (p less than 0.05) reduced to 1.2 +/- 0.3 ng/ml (n = 17) compared with vehicle treated rats (2.4 +/- 0.5 ng/ml; n = 18). The elevation in plasma i6-keto-PGF1 alpha seen 0.5 h (n = 17/group) after endotoxin infusion was not altered by trans 13-APT. trans-13-APT also significantly (p less than 0.05) attenuated the endotoxin-induced fall in platelet count (135 +/- 27 X 10(3)/mm3 vs. 350 +/- 65 X 10(3)/mm3 and hypoglycemia (73 +/- 9 vs. 97 +/- 7 mg/dl), but not the leukopenia. Since the reticuloendothelial system may be an important source of iTxB2 and i6 keto-PGF1 alpha during endotoxemia, in vitro studies were conducted with adherent peritoneal cells. High concentrations of trans-13-APT (50 and 100 microM) significantly reduced (p less than 0.05) basal but not endotoxin-induced synthesis of iTxB2 and i6-keto-PGF1 alpha by isolated adherent rat peritoneal cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580131 TI - Blood pressure and heart rate response to central beta-blockade in conscious rats with glucocorticoid-induced hypertension. AB - The beta-adrenergic antagonist propranolol, administered subcutaneously to conscious adrenalectomized rats made hypertensive by exogenous glucocorticoids, has been shown to induce acutely a marked fall in blood pressure and heart rate. These animals almost completely lacked circulating epinephrine. Because both changes were closely related, it was suggested that in this model of hypertension propranolol acts via a central mechanism. To test this hypothesis, we now administered sotalol (300 micrograms) intracerebroventricularly to unanesthetized adrenalectomized rats with glucocorticoid-induced hypertension (this hydrophilic beta-blocking agent does not cross the blood-brain barrier). The same experiments were also performed in sham-operated glucocorticoid-hypertensive rats. On the day of the study, there was no significant difference between adrenalectomized and sham-operated groups of rats in intraarterial pressure and heart rate. Sotalol increased blood pressure and significantly slowed heart rate during the 60-min observation period, both in adrenalectomized and sham-operated rats. Sotalol's vehicle had no blood pressure effect and caused a transient heart rate acceleration in rats with, as well as without, circulating epinephrine. These results therefore suggest that the previously observed enhanced effect of peripherally administered propranolol in the absence of detectable circulating epinephrine, in this model, is not mediated centrally. PMID- 2580132 TI - The effects of verapamil on the electrophysiology of the intact immature mammalian heart. AB - The electrophysiologic effects of intravenous verapamil were compared in six intact neonatal puppies ages 3-15 days and in adult dogs. Utilizing standard intracardiac recording and programmed stimulation techniques, sinus and AV nodal function and atrial and ventricular refractory periods were determined following incremental intravenous doses of 0.075 mg/kg, 0.15 mg/kg, and 0.30 mg/kg of verapamil. In the neonate, intravenous verapamil resulted in a significant increase of the sinus cycle length (37 +/- 6%) but no changes occurred in either the percent sinus node recovery time or the corrected sinus node recovery time. The atrial effective refractory period was prolonged by verapamil (32 +/- 12%). Concerning atrioventricular (AV) nodal function, verapamil produced a small but significant prolongation of resting AH interval (50.5 +/- 2.4 ms (control) versus 57.3 +/- 4.7 ms post 0.30 mg/kg) and a dose-related prolongation of the paced cycle length resulting in AV nodal Wenckebach (170 +/- 12.8 ms control, 190 +/- 10.3 ms post 0.075 mg/kg, 215.8 +/- 13.0 ms post 0.15 mg/kg and 246.7 +/- 22.8 ms post 0.30 mg/kg). The effective refractory period (ERP) and functional refractory period (FRP) of the atrioventricular node (AVN) were prolonged in a dose dependent fashion (ERP-AVN: 75 +/- 19% increase, FRP-AVN: 42 +/- 14% increase). Retrograde conduction, present in all six neonates, was completely abolished in four of six subjects and significantly prolonged in one other puppy by verapamil. No changes in ventricular refractory periods were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580133 TI - Effects of intracoronary nifedipine on blood flow and segment shortening in normal and ischemic myocardium: potentiation by ischemia of the negative inotropic effect. AB - The effects of intracoronary nifedipine on myocardial blood flow (flow probe or microspheres) and regional function (ultrasonic crystals in subendocardium) were examined both in the normal myocardium and in myocardium made ischemic by a partial coronary occlusion in the open-chest anesthetized dog. In a first group of experiments (n = 7), without ischemia, nifedipine infused into the left anterior descending coronary artery (LAD) during a 1-min period (doses 0.75-8 nmol/kg body weight) decreased coronary vascular resistance with a maximal effect at 4 nmol/kg. Systolic segment shortening was decreased from 10.7 to 7.4% (p less than 0.05) by 6 nmol/kg, whereas lower doses had no effect. In a second experimental group (n = 7), a partial LAD occlusion was applied to decrease subendocardial segment shortening by about 50%. Nifedipine (2 nmol/kg) injected into the partially occluded LAD induced a marked segmental bulging during early systole and systolic segment shortening was eliminated (from 4.2 to -3.1%, p less than 0.02) in the LAD-dependent myocardium. Concomitant with the decreased regional function, nifedipine caused a transmural redistribution of myocardial blood flow in the ischemic area, the endocardial/epicardial blood flow ratio increasing from 0.49 to 0.61 (p less than 0.02). It is concluded that ischemia potentiates the direct depressant effect of nifedipine on myocardial regional function. PMID- 2580134 TI - Endothelium-removal decreases relaxations of canine coronary arteries caused by beta-adrenergic agonists and adenosine. AB - Experiments were designed to investigate the importance of the endothelium in relaxation of isolated coronary arteries caused by beta-adrenoceptor agonists or adenosine. Rings of canine left circumflex coronary arteries were suspended for isometric tension recording in organ chambers filled with physiological salt solution. Norepinephrine, isoproterenol, adenosine, acetylcholine, and sodium nitroprusside caused relaxations of control rings contracted with prostaglandin F2 alpha or KCl. The relaxations to all substances tested were relatively smaller during contractions evoked by KCl than those caused by prostaglandin F2 alpha. Mechanical removal of the endothelium abolished the relaxations caused by acetylcholine, reduced those caused by the catecholamines and adenosine, and did not affect the relaxations to sodium nitroprusside during contractions to prostaglandin F2 alpha. Endothelium-removal did not affect relaxations to beta adrenergic agonists or adenosine during contractions to KCl or after pretreatment of the arteries with indomethacin. Indomethacin did not affect responses to acetylcholine or sodium nitroprusside, but augmented those in response to beta adrenoceptor stimulation and adenosine. These results suggest that the endothelial cells of the canine coronary artery produce a signal in response to beta-adrenergic agonists and adenosine, which facilitates the direct inhibitory action of these substances on vascular smooth muscle. PMID- 2580135 TI - Evaluation of the efficacy of slow-release nifedipine in systemic hypertension by ambulatory intraarterial blood pressure monitoring. AB - We assessed the effect on blood pressure of administration of slow-release nifedipine tablets (20 mg) by continuous intraarterial blood pressure monitoring (Oxford system) in 10 patients with untreated essential hypertension. Blood pressure was recorded under control conditions and during nifedipine therapy. During each monitoring period patients were instructed to perform various types of exercise. The initial dose of nifedipine was 20 mg twice a day (8:00 a.m. and 8:00 p.m.). For patients in whom arterial pressure control was not achieved, the dose of the drug was increased at weekly intervals, first to 40 mg in the morning and 20 mg at night and then to 40 mg twice a day. The average daily dose was 52 mg. Nifedipine twice a day significantly reduced systolic and diastolic blood pressures both during the day and during the night. The rise in blood pressure due to dynamic or isometric exercise or to mental testing was blunted. Heart rate did not change. Orthostatic hypotension was not observed, and there were only minor side effects, which did not require withdrawal of the patient from the trial. Bioavailability of nifedipine from this preparation was satisfactory, as shown by plasma concentrations which remained constantly in the therapeutic range. Thus, slow-release nifedipine given twice a day represents an effective treatment in patients with essential arterial hypertension. The reduced frequency of administration required may improve patient compliance with this treatment. PMID- 2580137 TI - Improved recovery of myocardial segment function following a short coronary occlusion in dogs by nicorandil, a potential new antianginal agent, and nifedipine. AB - The effects of nicorandil [SG-75, 2-nicotinamidoethyl nitrate (ester)] and nifedipine on the recovery of myocardial segment shortening were compared to a vehicle-treated group following a short occlusion (15 min) of the left anterior descending coronary artery (LAD) and reperfusion (5 h). The relationship between myocardial blood flow and myocardial segment shortening was examined by means of the radioactive microsphere technique and sonomicrometry. Nicorandil (100 micrograms/kg followed by 25 micrograms/kg/min, i.v.) or nifedipine (3 micrograms/kg followed by 1 microgram/kg/min, i.v.) was administered 10 min prior to and throughout the occlusion period. Both drugs produced similar decreases in mean arterial pressure (approximately 25 mm Hg) during LAD occlusion. Similar degrees of ischemia (flow deprivation) were produced in the vehicle, nicorandil, and nifedipine groups; however, nicorandil produced a significantly greater decrease in the heart rate-left ventricular systolic pressure product during coronary occlusion. During reperfusion of the LAD there was no difference in the hemodynamics of the vehicle, nicorandil, or nifedipine groups. Neither drug altered myocardial blood flow to the ischemic region during the occlusion or reperfusion period when compared to the vehicle-treated group; however, both nicorandil and nifedipine pretreatment significantly improved recovery of percentage of segment shortening of the ischemic region. Nicorandil improved the recovery of function (percentage of segment shortening) to a greater extent than did nifedipine throughout the reperfusion period, most likely because of the greater decrease in afterload produced by nicorandil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580136 TI - Cardiovascular effects of the metabolites of diltiazem in dogs. AB - The effects of diltiazem and some of its metabolites on the cardiovascular system were studied in anesthetized dogs and in blood-perfused canine papillary muscles. The metabolites included N-desmethyldiltiazem (MA), a newly discovered major metabolite; desacetyldiltiazem (M1); desacetyl MA (M2); O-desmethyl M1 (M4); and O-desmethyl M2 (M6). In the anesthetized dog, diltiazem and its metabolites produced a dose-dependent increase in coronary blood flow, decreases in blood pressure and heart rate, and an increase in left ventricular dP/dtmax. The ranking of coronary-vasodilating activity of diltiazem and its metabolites, in decreasing order, was diltiazem, M1, MA, M2, M4, and M6. The effects of the metabolites were more selective for coronary vasodilation than for hypotension, but their selectivities were less than that of diltiazem. Coronary vasodilation and hypotension with diltiazem and MA were of longer duration than those with their corresponding desacetyl metabolites. By close arterial administration to the blood-perfused canine papillary muscle preparation, diltiazem and its metabolites also produced coronary-vasodilating actions, whereas the negative inotropic actions were very weak. The present study revealed that the cardiovascular properties of some of diltiazem's metabolites are qualitatively the same as those of diltiazem, but the activity of diltiazem is the most potent, and MA is less active than M1. PMID- 2580139 TI - Experimental coronary artery thrombosis in the absence of thromboxane A2 synthesis: evidence for alternate pathways for coronary thrombosis. AB - The actions of the thromboxane synthetase inhibitor, U-63557A, were evaluated in vivo in anesthetized open-chest dogs by inducing left circumflex coronary artery (LCCA) thrombosis with low amperage electrical stimulation (100 microA for 6 h) of the intimal surface of the vessel, and ex vivo by assessing platelet aggregation and TXB2 production. U-63557A, 10 mg/kg + 5 mg/kg/h i.v., reduced ex vivo platelet aggregation in response to arachidonic acid (0.65 mM) by 93 +/- 2% (p less than 0.05, means +/- SEM), whereas the concurrent formation of TXB2 was decreased by 78 +/- 8% (p less than 0.05). TXB2 concentration also was reduced significantly in vivo as measured from coronary sinus blood samples; however, 6 keto-PGF1 alpha concentration was unchanged from predrug values. Despite the significant inhibition of platelet aggregation and TXB2 production, thrombus mass was not reduced: control, 32.0 +/- 5.9 mg (n = 7); U-63557A, 30.8 +/- 12.0 mg (n = 5, p = NS). These results suggest that U-63557A effectively inhibits TXA2 synthetase, but lacks antithrombotic activity in our experimental model. Therefore, substances other than TXA2 may be capable of mediating occlusive coronary artery thrombosis. PMID- 2580138 TI - Sympathetic control of myocardial oxygen balance in dogs mediated by activation of coronary vascular alpha 2-adrenoceptors. AB - Recent observations on sympathetic constriction of the poststenotic coronary bed without dilatory reserve indicate the involvement of postsynaptic alpha 2 adrenoceptors, which are commonly regarded as noninnervated, hormonal receptors. Therefore, we characterized the vascular alpha-adrenoceptor activated during the competition between sympathetic constriction and metabolic dilation of the nonstenosed coronary bed by analyzing myocardial oxygen balance. In 39 anesthetized, spinalized open-chest dogs with bilateral cervical vagotomy, the left decentralized stellate ganglion was stimulated while mean aortic pressure was kept constant. Stimulation at 1 and 10 Hz lowered coronary venous oxygen saturation by 2.5 +/- 0.3 (SEM) and by 11.1 +/- 0.8 saturation %, respectively, in experiments under beta-blockade (4 mg/kg nadolol, n = 21). In experiments without beta-blockade (n = 18), the saturation response was similar. Under beta blockade, alpha 2-blockade by rauwolscine (0.03 and 0.3 mg/kg) attenuated the decline in saturation induced by 10 Hz stimulation to 0.56 +/- 0.08 (p less than 0.01) of the control response and to 0.30 +/- 0.06 (p less than 0.001), respectively, whereas alpha 1-blockade by prazosin (0.012 and 0.12 mg/kg) modified this response only to 0.94 +/- 0.06 (NS) and to 0.75 +/- 0.08 (0.1 greater than p greater than 0.05). Without beta-blockade, similar attenuations to 0.36 +/- 0.07 (p less than 0.001) by 0.3 mg/kg rauwolscine and to 0.80 +/- 0.09 (NS) by 0.12 mg/kg prazosin were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580140 TI - Comparative cardiac electrophysiologic study of PK 10139, a new antiarrhythmic agent, and quinidine in anesthetized dogs: plasma concentration-response relationships. AB - Cardiac electrophysiologic effects of PK 10139 (PK), a new quinoleic antiarrhythmic agent, were compared with those of quinidine sulphate (Q) after three cumulative intravenous doses of 0.75, 1.5, and 3 mg/kg of PK and 5, 10, and 20 mg/kg of Q in anesthetized dogs. A control group of animals received saline solution only. Both PK and Q provoked an increase, correlated with plasma concentrations, in atrionodal (St-H), His-Purkinje system (HV), and auriculoventricular (QS) conduction times, and auricular effective and functional refractory periods (AERP, AFRP). The effects of PK on conduction times were more marked than those of Q. Slopes of the plasma concentration-effect curves were similar for the two drugs for HV and QS but different for St-H. PK was 42.5 times more potent than Q in increasing HV and 46 times more potent than Q in increasing QS. Effects of PK on AFRP and nodal FRP did not differ from those observed in control animals. These findings demonstrate more marked effects of PK, when compared with Q, at doses 6.7 times lower and at plasma concentrations 15 to 42 times less, without chronotropic effects or significant alterations in blood pressure, and without adverse reactions on the central nervous system. PMID- 2580141 TI - A comparison of the cardiotonic effects of AR-L115 and AR-L57: evidence for distinct inotropic mechanisms. AB - AR-L57 and AR-L115 have been of interest as inotropic agents for management of heart failure. Although their physiological effects are well documented, their mechanism(s) of action are unclear. Both AR-L57 and AR-L115 increased contractile force of cat papillary muscles in concentration-dependent manners; these effects were independent of either alpha- or beta-adrenoceptor stimulation. To determine if these effects occurred via a cAMP-dependent mechanism, cardiotonic actions were studied in the presence of carbachol. Muscarinic stimulation of papillary muscles attenuated contractile responses to AR-L115 thus implying a cAMP-mediated response. By contrast, carbachol did not alter the dose-response profile to AR L57. In addition, AR-L115 potentiated the inotropic actions of isoproterenol whereas AR-L57 was ineffective. Both AR-L57 and ouabain increased diastolic resting tension in papillary muscles--a phenomenon associated with a state of Ca2+ overload; AR-L115 was without effect. In anesthetized dogs, i.v. AR-L57 and AR-L115 increased contractility and heart rate while reducing mean arterial blood pressure. Both agents had similar rates of onset (10-15 s) and durations of action (40-60 min). Although in vitro studies clearly indicate that AR-L57 and AR L115 enhance inotropic state by distinct mechanisms, their in vivo cardiovascular profiles are comparable. PMID- 2580143 TI - Frequency-dependence of Vmax in K-depolarized guinea pig ventricle: effects of nifedipine and verapamil. AB - Right ventricular strips from guinea pig hearts were used to compare the effects of nifedipine and verapamil on the maximal upstroke velocity (Vmax) of rapid depolarization in potassium-depolarized preparations. The Vmax was used as an indirect measure of the slow inward current (Isi). Barium (0.8 mM) was added to the Tyrode solution to restore excitability of the K-depolarized tissue. The effects of nifedipine and verapamil on rested state Vmax (VmaxRS), frequency dependent changes in Vmax, and recovery of Vmax as a function of diastolic interval were studied. The depression of Vmax at rested state (RS), following 3-5 min rest, was concentration-dependent for both drugs, although the effect of nifedipine was greater. The percentage depression of VmaxRS by nifedipine was 24.3 +/- 6.4 at 10(-8)M, 51.3 +/- 2.6 at 5 X 10(-8)M, and 74.0 +/- 1.0 at 10( 7)M. For verapamil the values were 6.2 +/- 3.8 at 10(-7)M, 13.1 +/- 0.9 at 5 X 10(-7)M, and 42.0 +/- 0.5 at 10(-6)M. The depression of Vmax by each drug was frequency-dependent over a range from 0.05 to 2.0 Hz. Frequency-dependence was quantitatively greater with verapamil. The kinetics of recovery of Vmax were assessed by means of paired stimuli given at varying diastolic intervals during recovery from a RS depolarization. The recovery curve was biexponential. In the drug-free condition, the time constant for the first phase of recovery (Tr1) was 140 +/- 12 ms and the time constant for the second phase (Tr2) was 2689 +/- 146 ms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580142 TI - Separation of the coronary vasodilator from the cardiac effects of PN 200-110, a new dihydropyridine calcium antagonist, in the dog heart. AB - Coronary vasodilator and cardiac effects of PN 200-110 were compared by use of isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. PN 200-110 was administered intraarterially. In all preparations PN 200-110 produced an increase in coronary blood flow. In SA node preparations, the drug produced a decrease in sinus rate and atrial standstill as well, but only in large doses. The dose that produced a 15% (nearly half-maximum) decrease in sinus rate was about three times the dose that doubled coronary blood flow. In AV node preparations, the drug produced an increase in AV conduction time and, in large doses, second- or third-degree AV block only when it was injected into the artery supplying the AV node. The dose that produced a 15% (nearly half-maximum) increase in AV conduction time was approximately 12 times the dose that doubled coronary blood flow. In paced papillary muscle preparations, the drug produced a decrease in the force of contraction. However, the dose that produced a 50% decrease in the force of contraction of the papillary muscle was approximately 14 times the dose that doubled coronary blood flow. These effects of PN 200-110 were of long duration. The drug was entirely ineffective in changing the rate of ventricular automaticity. The order of selectivity of PN 200-110 was as follows: coronary blood flow greater than SA nodal automaticity greater than AV nodal conduction greater than ventricular muscle contraction. This cardiovascular profile of PN 200-110 is slightly different from that of PY 108-068, a compound closely related to PN 200-110 in chemical structure. PMID- 2580144 TI - Effect of ketanserin on the kinetics of digoxin and digitoxin. AB - The influence of the serotonin antagonist ketanserin on the kinetics of digoxin and digitoxin were evaluated in healthy volunteers. Subjects received a single intravenous dose of digoxin (1.25 mg) or of digitoxin (1.0 mg) on two occasions: once in the control state, and again during treatment with ketanserin, 40 mg twice daily. Ketanserin caused a prolongation of digoxin elimination half-life (50 versus 40 h) and reduction in clearance (2.4 versus 3.7 ml/min/kg), but differences were not significant. For digitoxin, ketanserin caused a small but significant (p less than 0.005) increase in volume of distribution (0.89 versus 0.78 L/kg), but no significant effect on half-life (7.0 versus 6.8 days), or clearance (0.063 versus 0.059 ml/min/kg). Thus, ketanserin coadministration is not likely to alter steady-state concentrations of digoxin or digitoxin during clinical use of these two digitalis glycosides. PMID- 2580145 TI - Prenalterol as a selective cardiostimulant: differences between organ and receptor selectivity. PMID- 2580146 TI - Influence of Bay k 8644 on pressor effects of B-HT 920 and cirazoline in pithed cats. AB - We studied interactions between the putative calcium entry promotor Bay k 8644 and alpha 1-adrenoceptor-mediated increases in diastolic pressure elicited by cirazoline as well as alpha 2-adrenoceptor-mediated pressor responses induced by B-HT 920 in pithed cats. Bay k 8644 (0.01-1 mg/kg, i.a.) did not affect the log dose-pressor response curve of cirazoline, but slightly potentiated the increase in diastolic pressure elicited by B-HT 920. After attenuation of the B-HT 920 induced pressor effects by the calcium entry blocker nifedipine (0.1 mg/kg, i.a.), Bay k 8644 (0.1 mg/kg, i.a.) strongly enhanced the pressor response. The increase in diastolic pressure elicited by cirazoline was not affected by nifedipine (0.1 mg/kg, i.a.), and the addition of Bay k 8644 (0.1 mg/kg, i.a.) had no effect. We conclude that in contrast to the increase in diastolic pressure elicited by B-HT 920, calcium channels are not involved in the cirazoline-induced pressor responses in the pithed cat. The activation of the calcium channels by B HT 920 is already so efficient that it cannot be further enhanced by Bay k 8644. PMID- 2580147 TI - Electrophysiological effects of cyclic GMP on canine cardiac Purkinje fibers. AB - The effect of cyclic 3'5'-guanosine monophosphate (8-bromo-cGMP) on action potential characteristics was investigated. Standard microelectrode techniques were used to study the effects of 8-bromo-cGMP on canine cardiac Purkinje fibers in vitro. Canine Purkinje fiber tissue preparations were exposed to increasing concentrations of 8-bromo-cGMP (10(-6), 10(-5), 10(-4) M). The action potential duration at 50% (APD50) and 90% (APD90) repolarization, resting membrane potential (RMP), action potential amplitude (APA), rate of rise of phase 0 (Vmax), spontaneous rate (SR), escape time (ET), and effective refractory period (ERP) did not change at these concentrations of 8-bromo-cGMP. The effect of 8 bromo-cGMP on isoproterenol (10(-7) M) treated Purkinje fibers was tested. Predictably, isoproterenol shortened APD and ERP and increased SR. APD or ERP shortening was not affected by 8-bromo-cGMP, but the increase in SR produced by isoproterenol was prevented. Eleven of sixteen Purkinje fiber preparations treated with isoproterenol alone became spontaneously arrhythmic, whereas none of six treated with 8-bromo-cGMP and isoproterenol became arrhythmic (p less than 0.05). Slow-response action potentials elicited by potassium depolarization and catecholamines were abbreviated and eventually abolished by 8-bromo-cGMP. In conclusion, 8-bromo-cGMP has no effect on action potential characteristics in normally polarized canine Purkinje fibers but depressed slow response action potentials. The effects of isoproterenol on SR are antagonized and the production of arrhythmias in this model are prevented by 8-bromo-cGMP. PMID- 2580148 TI - Persistent tissue converting enzyme inhibition following chronic treatment with Hoe498 and MK421 in spontaneously hypertensive rats. AB - Inhibition of angiotensin II generation in the plasma does not fully explain the antihypertensive effects of converting enzyme (CE) inhibitors. Thus, we investigated the role of CE inhibition in the tissue for the antihypertensive action of these drugs. After discontinuation of 4 weeks of oral treatment with either Hoe498 (3 mg/kg/day) or MK421 (30 mg/kg/day) in spontaneously hypertensive rats (SHRSP), the reduced pressor response to intravenous angiotensin I was normalized within 1 day, although systolic and diastolic blood pressure remained decreased during a 1 week post-treatment follow-up period. Two weeks of oral treatment with Hoe498 (1 mg/kg/day) and MK421 (30 mg/kg/day) in SHRSP lowered blood pressure markedly and inhibited CE in the plasma (43% and 22%), lung (85% and 33%), kidney (76% and 76%), aortic wall (75% and 48%), and (with Hoe498) in the heart (55%). After drug discontinuation, blood pressure remained decreased for an additional 2 weeks, whereas plasma CE was normal or elevated during the follow-up period. However, tissue CE activity measured 1 week after drug withdrawal was still inhibited in the aortic wall (67% and 30%) and in the kidney (48% and 41%). These results support the hypothesis that the prolonged antihypertensive action of CE inhibitors may be related to persistent CE inhibition in tissues such as vascular wall and kidney. Further, the data support the importance of CE inhibition at target sites other than plasma and lung vascular endothelium. PMID- 2580149 TI - Differential large and small vessel responses to serotonin in the dog hindlimb in vivo: role of the 5HT2 receptor. AB - Serotonin (5HT) constricts large arteries in vitro, an effect which seems contrary to 5HT-induced increases in blood flow observed in vivo. We used angiography to assess large artery responses, and blood flow (Q, electromagnetic flowmeter) to assess arteriolar responses to 5HT, norepinephrine (NE), and antagonists in the femoral circulation of the intact, anesthetized dog. 5HT constricted large arteries at a threshold dose of less than 10 micrograms/min, giving a 45 +/- 3% reduction of popliteal artery diameter at 100 micrograms/min (p less than 0.001). NE failed to constrict large arteries. With 100 micrograms/min 5HT, Q increased (delta Q = 108 +/- 26 ml/min; p = 0.001). NE decreased Q. Ketanserin, a 5HT and alpha 1-adrenergic antagonist, exerted a dose dependent inhibition of 5HT-induced large artery constriction. Methysergide partially blocked the 5HT-induced large artery constriction. Ketanserin potentiated the Q response to 5HT whereas higher doses of methysergide reduced the Q response to 5HT. Neither indomethacin nor propranolol altered either response. Failure of NE to constrict large arteries in vivo and ketanserin antagonism of constriction produced by 5HT suggest the response to 5HT involves the 5HT2 receptor. No role for the 5HT2 receptor in blood flow responses is suggested. These observations may have implications for therapy of occlusive vascular disease. PMID- 2580150 TI - Electrophysiological effects of bethanidine sulfate on canine cardiac Purkinje fibers and ventricular muscle cells. AB - Bethanidine sulfate is a congener of bretylium tosylate, which has been reported to have antiarrhythmic and antifibrillatory effects. We studied the effects of bethanidine on transmembrane potentials recorded from canine Purkinje fibers and ventricular muscle cells, using standard microelectrode techniques. Normal Purkinje fibers were exposed to bethanidine (10-80 mg/L) for 30-40 min. Bethanidine produced dose-dependent decreases in the maximal rate of depolarization (MRD) and over-shoot of phase 0, but did not affect maximum diastolic potential (MDP). Action potential plateau duration (APD, to -60 mV) was decreased by bethanidine at all cycle lengths of stimulation between 1,000 and 300 ms. Bethanidine depressed the membrane responsiveness curve, and its effects on MRD showed marked use dependence. In ventricular muscle cells, bethanidine 20 mg/L decreased MRD but did not affect MDP or APD. The rate of normal automaticity in Purkinje fibers with MDPs greater than -85 mV was increased to 21.5 +/- 5.6 beats/min after exposure to bethanidine (10 mg/L for 30 min) from control values of 10.2 +/- 5.3 beats/min. Abnormal automaticity (MDPs = -40 to -60 mV) was induced in Purkinje fibers by superfusion with Tyrode solution containing 0.25 mM BaCl2; this activity also was accelerated after exposure to bethanidine 10 mg/L. The effects of bethanidine on automaticity are similar to those of bretylium, and may be caused by release of endogenous catecholamines. In contrast, the effects of bethanidine on action potentials of normal (driven) Purkinje fibers are markedly different from those of bretylium, and resemble those of lidocaine after 30-60 min of exposure. PMID- 2580151 TI - Effect of sodium depletion on the release of [3H]norepinephrine from central and peripheral tissue of Wistar-Kyoto and spontaneously hypertensive rats. AB - To study the relationship between sodium intake, the sympathetic nervous system, and hypertension, we studied the effects of a 7-9 day dietary restriction of sodium in three different ages of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Field-stimulated [3H]norepinephrine ( [3H]NE) release was measured in portal vein, anterior hypothalamus, and the A2 region of the nucleus tractus solitarius (NTS) of 5- to 6-, 10- to 11-, and 28- to 30- week-old SHR and age-matched WKY. A low-sodium diet (0.05% Na+, control 0.5% Na+) significantly lowered stimulated [3H]NE release from portal vein and anterior hypothalamus in SHR and WKY at all three ages. However, release from the A2 region was not altered by sodium restriction. The results of the present study suggest that lowered dietary sodium can selectively alter norepinephrine release in both the peripheral and central sympathetic nervous system of SHR and WKY. The results also suggest that the SHR at 5-6 weeks are more sensitive to altered dietary sodium than are age-matched WKY. PMID- 2580152 TI - Effects of vasopressin on heart rate in conscious rabbits. AB - The effects of vasopressin on heart rate and on the baroreceptor-heart period reflex were assessed during graded intravenous infusions of arginine vasopressin. Infusions which elevated plasma arginine vasopressin to 200 pg/ml had no effect on blood pressure, but induced a fall in heart rate and cardiac output and an increase in peripheral resistance. These effects were unaltered by vagal blockade with methylscopolamine and cardiac sympathetic blockade with propranolol but were prevented by pretreatment with a specific vascular antagonist to vasopressin, d(CH2)5Tyr(Me)AVP. Baroreflex control of heart rate was studied during vasopressin infusion by monitoring the heart period responses to graded changes in mean arterial blood pressure produced by inflation of balloon occluders around the abdominal aorta and thoracic vena cava. Elevation of plasma arginine vasopressin to 50 pg/ml and 200 pg/ml had no significant effect on the slope or sensitivity of the baroreceptor-heart period reflex but increased the maximum bradycardia elicited in response to large increases in blood pressure. We conclude that at physiological levels, arginine vasopressin has a direct cardiodepressant action that is not dependent on cardiac vagal or sympathetic activity. Our results indicate that arginine vasopressin increases the maximum bradycardia that can be elicited through baroreceptor reflexes but does not alter the slope relating change in heart rate to change in blood pressure. PMID- 2580153 TI - beta-Adrenergic receptors, adenylate cyclase activity, and cardiac dysfunction in the diabetic rat. AB - Cardiomyopathy is a complication of human diabetes mellitus. The relationship of cardiac function to the beta-adrenergic receptor and catecholamine-stimulated adenylate cyclase activity was investigated in the streptozotocin-diabetic rat. beta-Adrenergic receptor number in cardiac membranes from diabetic rats was reduced. After 2 weeks of diabetes, the response of adenylate cyclase to isoproterenol stimulation was not altered. Cardiac contractile function assessed by the maximum rate of rise of left ventricular pressure (LV dP/dtmax) in an open chest anesthetized rat was also unchanged from control at 2 weeks. However, after 4 weeks of diabetes, the sensitivity of adenylate cyclase to isoproterenol stimulation was depressed and abnormalities in cardiac contractility were noted, including a depressed response of LV dP/dtmax to graded isoproterenol infusion. These studies suggest that alterations in beta-adrenergic receptors and their coupling to adenylate cyclase may be important in the development of diabetic cardiomyopathy. PMID- 2580155 TI - Cardioselective beta-blockade with atenolol and acebutolol following acute myocardial infarction: a multiple-dose haemodynamic comparison. AB - In patients with acute myocardial infarction the haemodynamic relevance of the ancillary pharmacological properties of cardioselectivity and of intrinsic sympathomimetic activity (ISA) possessed by beta-blocking drugs is unclear. The dose-response effects of atenolol and acebutolol, two cardioselective compounds, the latter also possessing a degree of ISA, were therefore compared in a single blind, dose-response, crossover study in patients within 18 h of suffering an uncomplicated acute myocardial infarction. The logarithmic cumulative dosage schedule achieved plasma concentrations in the clinical therapeutic ranges for both atenolol (0.05 +/- 0.04-0.19 +/- 0.03 micrograms/ml) and acebutolol (0.22 +/ 0.14-0.8 +/- 0.29 micrograms/ml). Incremental doses of intravenous atenolol (cumulative, 1-8 mg) resulted in significant decreases in systolic blood pressure, heart rate, cardiac output, stroke volume, and stroke work index (p less than 0.01 for each). Pulmonary artery occluded pressure (p less than 0.05) and systemic vascular resistance (p less than 0.01) increased. Incremental doses of intravenous acebutolol (cumulative, 10-80 mg) also resulted in significant decreases in systolic blood pressure, heart rate, cardiac output, stroke volume, and stroke work index (p less than 0.01 for each). Systemic vascular resistance increased (p less than 0.01); there was no consistent change in the pulmonary artery occluded pressure. Within the limits of the experimental protocol, the additional property of ISA possessed by acebutolol resulted in no statistically significant haemodynamic differences from atenolol. This may reflect either an insufficient degree of ISA possessed by acebutolol to confirm the original hypothesis, or its haemodynamic irrelevance in the presence of the increased sympathetic tone that is frequently present following acute myocardial infarction. PMID- 2580154 TI - Actions of two new bradycardic agents, AQ-AH 208 and UL-FS 49, on ischemic myocardial perfusion and function. AB - The effects of continuous infusions (30 min) of two new bradycardic agents, AQ-AH 208 (3,4-dihydro-6,7-dimethoxy-2-(3-((2-(3,4 dimethoxyphenyl) ethyl)-amino methyl) propyl)-1(2H)-isochinolinon) (10 and 25 micrograms/kg/min) and UL-FS 49 (1,3,4,5-tetrahydro-7,8-dimethoxy-3(3((2-(3,4-dimethoxyphenyl) ethyl) methylimino) propyl)-2H-3-benzazepin-2 on) (1.0 and 2.5 micrograms/kg/min) on ischemic myocardial perfusion and function were studied in anesthetized open chest dogs. Coronary stenosis was induced by narrowing an extracorporeal shunt between the carotid and left anterior descending coronary artery. Regional perfusion was measured by use of radioactive microspheres and regional myocardial function (% segment shortening) was assessed by sonomicrometry. AQ-AH 208 and UL FS 49 produced dose-dependent reductions in heart rate of 13 to 55 beats/min without prominent effects on left ventricular dP/dt, aortic blood pressure, and % segment shortening of the normally perfused area. In nonischemic myocardium, AQ AH 208 did not change transmural blood flow in spite of the bradycardia, whereas UL-FS 49 decreased flow. At the high infusion rate, ischemic subendocardial perfusion increased from 0.43 to 0.58 ml/min/g following UL-FS 49 and from 0.57 to 0.84 ml/min/g after treatment with AQ-AH 208. Consequently, endo/epi rose from 0.52 to 0.80 and 0.62 to 0.96, respectively. Atrial pacing abolished the effects of UL-FS 49 on ischemic myocardium whereas the effects of AQ-AH 208 were only partially reduced. Ischemic myocardial function deteriorated less during treatment with UL-FS 49 and was significantly improved following AQ-AH 208 as compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580156 TI - Dose-response following single administrations of a new cardiac performance enhancer RO 13-6438 in normal volunteers. AB - We assessed the changes in cardiovascular function in humans caused by RO 13 6438, a new drug that enhances cardiac performance, by means of noninvasive methods which included measurement of systolic time intervals and electrical impedance cardiography. Twelve healthy male volunteers received RO 13-6438 doses of 10 and 20 mg intravenously and 20, 40, and 60 mg orally according to a double blind, randomized, crossover, placebo-controlled design. A dose-dependent distinct enhancement in cardiac performance was seen. This was attributed to positive inotropism (shortening of heart rate-corrected electromechanical systole) and to a vasodilating action (decline of diastolic blood pressure and total peripheral resistance). In addition, the drug increased heart rate slightly. The cardiac effects were detectable for 6 h. To reach the average equivalent inotropic response over 6 h, the oral dose was approximately 1.8-fold of the i.v.; this indicated a high bioavailability of RO 13-6438. Transient color vision disturbances were reported mainly following the intravenous administration. The properties of RO 13-6438 suggests that it may be useful for treatment of heart failure. PMID- 2580157 TI - Regional hemodynamic effects of clonidine in congestive heart failure. AB - Regional and central hemodynamic variables were ascertained in 10 patients with congestive heart failure before and after the oral administration of clonidine. Following the 0.2 mg dose, renal, hepatic, and limb blood flow remained unaltered, whereas a reduction was noted in heart rate (10%), mean systemic (14%), and pulmonary capillary wedge pressures (27%). Cardiac index and systemic vascular resistance fell slightly, however the changes were not statistically significant. Higher dose clonidine (0.4 mg) elicited similar regional hemodynamic effects whereas systemic vascular resistance significantly diminished (21%) and cardiac index remained unchanged. In congestive heart failure, the central antihypertensive agent, clonidine, effects a significant reduction in preload (left ventricular filling pressure) and afterload (systemic blood pressure) without markedly altering other central and regional hemodynamic variables. PMID- 2580159 TI - Squibb symposium series number 1. Angiotensin converting enzyme inhibition in clinical practice. Geneva, June 22-23, 1984. PMID- 2580158 TI - Hemodynamic effects of ICI 118.587 (Corwin) in patients with mild cardiac failure after myocardial infarction. AB - The aim of this study was to compare the effects of intravenous ICI 118.587 (Corwin), a new cardioselective partial beta-agonist, and placebo given q. 12 h for 4 consecutive days, with invasive and noninvasive methods. Twelve patients with mild to moderate cardiac failure after a myocardial infarction were studied. We could not show any significant effect of Corwin on hemodynamics, systolic time intervals, heart rates, or blood pressures. We conclude that Corwin does not affect left ventricular function, as measured by hemodynamics and systolic time intervals, in the immediate postinfarction period in patients with mild to moderate heart failure. PMID- 2580160 TI - The case for treating mild hypertension. AB - Data are presented that define the risks of elevated blood pressure, both systolic and diastolic, and support the recent recommendations of the Third Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure in the United States that a consistently elevated pressure level above 140/90 mm Hg in adults should be lowered if possible. A summary of the major clinical trials, as well as a review of extensive data reported over the past 15-20 years, supports conclusions that mortality and morbidity are reduced, even in the mild hypertensive (diastolic BPs of 90-104 mm Hg), following blood pressure lowering to normotensive levels (less than 140-90 mm Hg). Numerous observations in the 1960s and 70s had established the benefits of treatment in patients with severe hypertension (diastolic BPs more than 115 mm Hg). The Veterans Administration studies also demonstrated that blood pressure lowering in patients with diastolic BPs above 105 mm Hg reduced mortality. More recently the 7-10-year U.S. Public Health Service Study and the Hypertension Detection and Follow-Up Program Study (HDFP) in the United States, and the Australian Study in Mild Hypertension, have demonstrated a decrease in cerebrovascular and a trend of a statistically significant decrease in overall cardiovascular mortality with effective blood pressure lowering.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580161 TI - High blood pressure: what level to treat? AB - Recent trials of the treatment of mild hypertension have suggested that there may be benefit from drug treatment of quite modest or borderline levels of pressure. Drug treatment of subjects with diastolic pressures over 95 mm Hg would pose a major problem in the efficient organization of such a long-term program and would also be costly. Perhaps about 350 patient years of treatment might be necessary to prolong one patient's life by 1 year. The side effects as well as the costs of such a program should make us cautious about offering such treatment solely on the results of measurement of arterial pressure. In people with diastolic pressures in the range of 90-100 mm Hg we should carefully consider several factors such as age, sex, cholesterol concentrations, diabetes, family history, and smoking habit which might also interact to identify particularly high risks and exclude those individuals with a particularly benign prognosis. The results of the more recent trials can give very little information about such subgroup analysis, which would be possible only with much larger samples. The untreated subjects with raised pressure should be carefully followed and offered advice on nondrug strategies such as weight reduction, treatment of lipid abnormalities, and reduction in dietary salt intake. This type of program demands careful, possibly computerized, records and follow-up. PMID- 2580162 TI - Angiotensin converting enzyme inhibition in clinical practice. Choice of initial treatment. AB - An important consideration in the choice of initial treatment is race. In a Veterans Administration study nadolol reduced blood pressure more in whites than in blacks, while the reverse was true with hydrochlorothiazide. Combining both drugs enhanced antihypertensive effectiveness and abolished the racial difference. The results of this and other studies suggest that for first drug selection, beta-blockers are indicated in whites and diuretics in blacks. Beta blockers are also indicated in all patients with prior myocardial infarction or with tachycardia. Thiazides are also used in combination with other antihypertensive drugs and in patients with heart failure. Reluctance to use thiazide diuretics stems from the possibility of hypokalemia-induced arrhythmias and long-term elevations of serum cholesterol. However, a causal relationship between hypokalemia and the incidence of arrhythmias is not well supported by physiologic or clinical evidence. Elevation of cholesterol appears to be transient, reverting back to pretreatment levels after 6-12 months of treatment. An alternative regimen which is both highly effective and well tolerated is the combination of small doses of both a thiazide diuretic and captopril. Perhaps less well tolerated, but useful where cost is the major consideration, is a thiazide followed by small doses of reserpine, if needed; this is an effective, low-cost treatment. Calcium channel blockers appear promising but require further evaluation. PMID- 2580163 TI - Angiotensin converting enzyme inhibition in clinical practice. Re-examination of step care: choice of first drug. AB - In any therapeutic situation, the choice of drug therapy depends on an estimation of relative risk and benefit. With respect to moderate hypertension, and with less certainty, mild hypertension, the use of drug therapy has resulted in a decrease in overall mortality, a decrease in the incidence of stroke and renal impairment, but little or no change in the incidence of ischemic heart disease. For several years, the choice of first drug in these situations has rested between thiazide diuretics and beta-adrenoceptor blocking agents. There is probably little to choose between these two groups in terms of efficacy, and equally there is little evidence that patient response to one or other agents can be predicted either on demographic or biochemical evidence. There are, however, several studies both in Africa and America suggesting that black patients have a relatively greater hypotensive response to thiazides than to beta-blockers. The adverse reaction profile of these two groups is quite different. There is currently much debate whether the administration of large doses of thiazide diuretics (for example, 10 mg bendrofluazide per day) may cause a constellation of metabolic side effects (hyperlipemia, hypokalemia, abnormal glucose tolerance, and hyperuricemia) which may result in an increase of the risk of developing coronary artery disease in spite of lowering blood pressure. Further, there is no good evidence that the hypotensive effect of diuretics is dose dependent. On the other hand, the evidence that beta-blockers when used as antihypertensive agents have a primary preventive effect for ischemic heart disease is currently very small.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580164 TI - Captopril versus enalapril maleate: a comparison of antihypertensive and hormonal effects. AB - The antihypertensive effects of captopril and enalapril maleate were studied over a 10-week period in 24 hypertensive patients randomized into captopril or enalapril treatment groups. Prestudy blood pressure was 171 +/- 4/109 +/- 1 mm Hg and after 4 weeks of hydrochlorothiazide 160 +/- 4/103 +/- 1 (p less than 0.05). With the addition of converting enzyme inhibitor to hydrochlorothiazide the blood pressure decreased at 3 h to 132 +/- 3/87 +/- 2 in the subjects. The diastolic blood pressure decreased acutely more with captopril (-24) than with enalapril ( 17) (p less than 0.05). After 10 weeks of combined therapy the depressor response was maintained (134 +/- 3/83 +/- 1) and there was no difference between the diastolic blood pressure in the two groups treated with captopril and enalapril. Acute and chronic responses of plasma renin activity, plasma aldosterone, and converting enzyme to the angiotensin-converting enzyme inhibitor were determined. There was a significant correlation between the acute fall in diastolic blood pressure and rise in plasma renin activity in patients treated with captopril but not with enalapril. In conclusion, there is an acute depressor response with converting enzyme inhibition which is more pronounced with captopril than with enalapril and which correlates with an increase in plasma renin activity. With more prolonged treatment, the two drugs show equivalent efficacy in reducing blood pressure, inhibiting angiotensin-converting enzyme, reducing aldosterone, and stimulating plasma renin activity. PMID- 2580165 TI - Angiotensin converting enzyme inhibition in clinical practice. The second step in "stepped-care": addition or substitution? AB - The step-wise addition of drugs in stepped-care therapy is based in good part on the need to control different pressor mechanisms in order to lower blood pressure effectively over a long period of time. These mechanisms include the primary mechanisms assumed to be responsible for the hypertensive process and subsequently, either the mechanisms missed by the first drug or the secondary mechanisms evoked by therapy. Although stepped-care therapy has proven effective for many, its rigid application misses the importance of control of systolic blood pressure and of reversal of cardiovascular hypertrophy as additional goals of treatment. Further, the addition of a second drug might mean, in some cases, that an ineffective first drug is continued for no apparent reason. Substitution rather than addition of drugs is a reasonable option. Moreover, the advent of newer drugs with multiple mechanisms of action suggests that a step-wise addition of drugs might not be needed if the list of first step drugs is reviewed with recent advances in mind. PMID- 2580166 TI - Angiotensin converting enzyme inhibition in clinical practice. A re-examination of stepped-care: a retrospective and a prospective. AB - Diuretics have so far enjoyed a prominent position in all stepped-care programs, as the preferred first choice drug in most American schemes or as an alternative first choice drug with respect to beta-blockers in the WHO scheme. Among various reasons for this prominence has been that antihypertensive drugs available until recently all gradually led to sodium and water retention, and therefore required to be combined with a diuretic. This is no longer true: several antihypertensive agents are available now that do not require combination with diuretics, these new agents including not only beta-blockers but also angiotensin-converting enzyme (ACE) inhibitors and calcium entry blockers. Furthermore, some concern about the metabolic effects of diuretics has recently been raised, especially because of the failure to prevent coronary heart disease by the current diuretic based antihypertensive regimens. Without denying the importance that diuretics have had in the past in making antihypertensive therapy successful and their continuing essential role in treating severe hypertension, it is likely, in my opinion, that in future years diuretics are going to be more often used as agents of second choice, mostly in combination with beta-blockers, ACE inhibitors, and, perhaps, some of the calcium blockers. In conclusion, although opinions of various experts about the sequence of choices between antihypertensive drugs may obviously differ, there is no doubt that the addition of new classes of effective agents, such as the ACE inhibitors and the calcium entry blockers, is making antihypertensive therapy more flexible and more easily suitable to the needs of individual patients. PMID- 2580167 TI - Quality of life and the patient's response to treatment. AB - Quality of life resides mainly in an individual's satisfaction with his role at work, at home, and in his community. Illness and treatment affect quality of life to the extent that they damage an individual's ability to perform these roles to his own satisfaction. Clinicians will increasingly have to take account of quality of life in assessing the effect of an illness and of their treatment for it. This is particularly so in chronic diseases for which there is no "cure" and in asymptomatic conditions, such as hypertension. PMID- 2580168 TI - Quality of life in hypertensive patients on different antihypertensive treatments: rationale for methods employed in a multicenter randomized controlled trial. AB - In measuring the quality of life and other such end points in a trial, it is widely recognized that poor methods and observer and subject bias may invalidate the results. The measurement of two aspects of the quality of life, activity and well-being, is attempted using methods which include valid, repeatable assessments that are also sensitive to the actions of pharmaceutical agents. Methods are described for use in a randomized controlled trial to measure three aspects of well-being: symptoms, activity, and psychological status. These methods are employed in a single-blind randomized trial of a combination of oxprenolol plus diuretic compared with captopril plus diuretic in 97 patients with mild to moderate hypertension. The patients are from West German centers involved in a multicenter European study. In 34 (35%) of the patients, well-being was assessed from a self-administered questionnaire, and in the remaining 63 patients the investigators interviewed the patients and asked the same questions. Data are presented at entry to the trial. The methods appeared to be successful at that stage and the results were comparable with those for similar studies in London. Activity, well-being, and psychological status were sufficiently correlated to suggest that the methods are valid estimates of certain aspects of the quality of life. However, two major problems remain. Less disability was reported when the questionnaires were completed by the investigators; and after randomization their nonblindness must raise doubts about the objectivity of interviewer-derived data. The results of the trial may have to be assessed solely from self-administered questionnaires. PMID- 2580169 TI - Once-daily administration of captopril and hypotensive effect. AB - The usual regimens of captopril--twice or thrice daily administration--are based on the duration of the decrease in plasma angiotensin II induced by captopril. In a study performed to evaluate the hypotensive effect of once daily captopril, 13 white patients with mild-to-severe uncomplicated hypertension were treated with one tablet of captopril 100 mg daily, taken 1-1.5 h before lunch, for 8 weeks. Arterial blood pressure was measured weekly, 22-23.5 h after medication. The patients' diet contained no more than 120 mmol/day of sodium. In the first week supine blood pressure fell from 210 +/- 3/128 +/- 4 (mean +/- SEM) to 179 +/- 5/116 +/- 5 mm Hg (p less than 0.001/p less than 0.01 compared with pretreatment). After the large decrease in the first week changes in systolic and diastolic pressures tailed off; they tended to fall towards stable values that would be maintained on prolonged treatment. At the end of the eighth week the supine values were 155 +/- 3/104 +/- 3 (p less than 0.001/p less than 0.001). Changes in erect blood pressure paralleled those in the supine posture. No side effects were detected. These results confirm that captopril is efficacious when given alone to patients with essential hypertension who are taking a low sodium diet. Blood pressures were not, however, reduced to normotensive levels. Captopril's hypotensive effect in once daily administration appears to be independent of its effects on circulating angiotensin II. Captopril alone 100 mg/day is thus indicated in essential hypertension and should be prescribed once daily to obtain the best possible compliance. PMID- 2580170 TI - The present molecules of converting enzyme inhibitors. AB - Since the end of 1976 ten orally active converting enzyme inhibitors [SQ 14,225 (captopril), MK 421 (enalapril), MK 422, MK 521 (lysinopril), RHC 3659, CGS 13945, CGS 13928C, CGS 14824A, Hoe 498, S 9490-3, and Ro 31-2848] have been evaluated by our group in normal volunteers. Their ability to blunt the pressor response to exogenous angiotensin I and their effect on the different components of the renin-angiotensin system were tested. This approach has made it possible to establish the efficacy of the different molecules and to predict with a considerable degree of accuracy onset and duration of action of the various compounds as well as the doses needed to treat hypertensive patients. All ten molecules were effective in blocking converting enzyme and thereby the pressor response to angiotensin I. Potency and time course of the inhibition varied considerably among the compounds. Thus, a number of highly effective angiotensin converting enzyme inhibitors are actually in clinical evaluation and several of them should become available for general clinical use within a few years. PMID- 2580172 TI - Influence of food on acute and chronic effects of captopril in essential hypertensive patients. AB - To determine if food reduces the hemodynamic and humoral effects of captopril in patients with essential hypertension, we performed two studies. In the acute study, 15 inpatients with uncomplicated essential hypertension randomly received a single oral dose of placebo or captopril (25 mg) while fasting or after eating, or captopril (50 mg) after eating. Blood pressure and heart rate were measured every 30 min up to 4 h (and up to 10 h in six out of the 15 patients), while plasma renin activity, plasma aldosterone, and serum angiotensin-converting enzyme were measured 2 h after dosing. Compared with placebo, captopril significantly reduced mean blood pressure (p less than 0.001), serum angiotensin converting enzyme (p less than 0.005), and aldosterone (p less than 0.001), increased plasma renin activity (p less than 0.05), and did not change heart rate; there was no difference between the fasting and the fed state. In the six patients followed up to 10 h, captopril both before and after food significantly and similarly reduced mean blood pressure up to 8 h (p less than or equal to 0.05). In the chronic study, 10 patients with uncomplicated essential hypertension, while having prolonged (3-12 months) treatment with captopril (50 mg twice a day), were asked to take captopril for 1 month 1 h before eating and for another month during or immediately after eating. The sequence was randomized, and blood pressure, heart rate, plasma renin activity, serum angiotensin-converting enzyme, and plasma aldosterone were measured at the end of each period 12 h after last dosing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580171 TI - Pharmacokinetics of captopril and its effects on blood pressure during acute and chronic administration and in relation to food intake. AB - Nine patients with essential hypertension treated with bendroflumethiazide were given captopril 25 mg orally on three occasions to study the pharmacokinetics and blood pressure effects. Study 1: acute and fasting; study 2 and 3: with and without concomitant food intake (randomized order) after chronic treatment with captopril 25 mg three times a day for 4-5 weeks. Total and non-protein-bound captopril were measured by high performance liquid chromatography. Baseline mean arterial pressure (MAP) was lower during chronic treatment. MAP reduction was slightly more pronounced initially with concomitant food intake but thereafter the reductions were similar for up to 12 h in the three studies. Mean values for maximal MAP reductions and peak plasma concentrations of captopril occurred at the same time, but individual values were not correlated with each other. Peak plasma concentrations and area under the curve (AUC) of total and non-protein bound captopril were slightly reduced with concomitant food intake. Chronic treatment did not consistently change the kinetics except for a slight prolongation of terminal half-life of non-protein-bound captopril. The AUC was higher during the chronic studies, probably owing to the baseline presence of captopril in plasma. It appears that captopril can be given twice daily and together with food without loss of blood pressure control in essential hypertension. PMID- 2580173 TI - The future of angiotensin-converting enzyme inhibitors. AB - After a brief introduction summarizing their historical development and the classification of angiotensin-converting enzyme inhibitors by chemical structure, the considerations involved in developing new and improved drugs of this pharmacologic class are discussed. These include properties such as the drug's potency, route of absorption and excretion, pharmacokinetics, drug disposition, and toxicity. Although increased potency, a traditional method for improving efficacy, can be achieved with angiotensin-converting inhibitors by introducing additional binding sites or by increasing the strength of binding at existing sites, safety testing has shown that with some compounds this approach may cause nephrotoxicity. Because renal disease is a common cause of hypertension and the two conditions frequently coexist, in some patients agents that are eliminated by both renal and hepatobiliary routes may be more desirable than those eliminated almost exclusively by the kidneys, such as captopril. This and other shortcomings of captopril have led to the development of two new angiotensin-converting enzyme inhibitors, zofenopril and fosfenopril, which are both in the early phase of clinical investigation. The former is an analog of captopril and the latter is classified as a first phosphinic acid angiotensin-converting enzyme inhibitor. Another possibility for the future is the incorporation of two therapeutic objectives into a single compound in the form of an angiotensin-converting enzyme inhibitory diuretic which, although chemically feasible, may be of questionable practical value. Also, the success of blood pressure control through intervention at the level of the renin-angiotensin-aldosterone system has created interest in the development of renin inhibitors. The primary stimulus for this avenue of investigation was the specificity of renin, which has only one substrate while converting enzyme has many. PMID- 2580174 TI - Hemodynamic effects of angiotensin-converting enzyme inhibitors in essential hypertension: a review. AB - Angiotensin-converting enzyme inhibitors are vasodilators that exert their beneficial hemodynamic effects in hypertension primarily by withdrawal of the vasoconstricting action of endogenous angiotension II. Although the magnitude of the initial decrease in vascular resistance depends on renin activity, the long term arterial blood pressure response does not appear to be influenced by initial renin levels. Cardiac output is not significantly altered by angiotensin converting enzyme inhibition in patients with mild-to-moderate hypertension, but a rise toward normal levels often occurs in patients with severe hypertension or heart failure. Although right and left heart filling pressures are not significantly altered, other evidence suggests that these agents increase venous capacitance. Patients with severe hypertension, for example, have shown increased forearm venous distensibility in response to angiotensin-converting enzyme inhibitors, and a decrease in the ratio of cardiopulmonary blood volume to total blood volume has been demonstrated in normotensive patients with heart failure. Several studies have shown improved renal blood flow after angiotensin-converting enzyme inhibition, suggesting that renal vascular resistance is reduced more than systemic resistance. Reflex tachycardia and other neurohumoral counterregulatory responses occur less frequently than with other vasodilators, because neither the renin-angiotensin-aldosterone nor the autonomic nervous system is activated by angiotensin-converting enzyme inhibition. PMID- 2580176 TI - Effects of acute and chronic angiotensin-converting enzyme inhibition on large arteries in human hypertension. AB - The effects of angiotensin-converting enzyme inhibition on large arteries have been examined in uncomplicated essential hypertensive patients (grade 1-2 WHO). These effects were determined from (a) changes in arterial compliance as measured from the slope of the decline in arterial pressure during diastole and (b) alterations in diameter of the brachial artery and blood flow velocity within its lumen, as assessed by pulsed Doppler velocimetry. Both acute and chronic ACE inhibition were accompanied by a significant increase in arterial compliance and a dilation of the brachial artery. This response might be related to changes in plasma and/or intraarterial angiotensin and/or to changes in plasma potassium. Whatever their mechanism, the arterial dilatation and increase in compliance would improve the buffering and the conducting functions of the large arteries, and these in turn may, if persistent, prove beneficial in possibly preventing arterial complications of hypertension. PMID- 2580175 TI - Angiotensin-converting enzyme inhibition: renal aspect. AB - Compelling arguments can be made for a local, intrarenal role as angiotensin's first action in phylogeny, with additional cardiovascular and endocrine responses arising later. Perhaps for that reason the vascular bed of the kidney is especially responsive to angiotensin II. Conversely, when the renin-angiotensin system is activated, as it is when sodium intake is restricted or diuretics are administered, the renal blood supply shows the most striking and consistent vasodilatation among vascular beds assessed after converting enzyme inhibition. When renal vascular tone is increased in patients with essential hypertension, converting enzyme inhibitors induce a potentiated acute renal vascular response: renal blood flow increases more than it does in normal subjects, with an associated consistent early increase in sodium excretion and an occasional increase in glomerular filtration rate. Reduced aldosterone release consequent on the block of angiotensin II formation also contributes to the natriuresis and results in positive potassium balance. With long-term therapy renal function tends to be well maintained. The response to converting enzyme inhibition in renal artery stenosis is more complex: as perfusion pressure distal to the stenosis falls there is typical afferent arteriolar dilatation and glomerular capillary pressure tends to be maintained by a rise in postglomerular resistance. To the extent that this is angiotensin mediated, suppression of angiotensin formation can reduce glomerular capillary pressure and thus filtration rate. This is well tolerated in the patient with unilateral stenosis and a healthy contralateral kidney, but can provoke renal failure where the stenosis is bilateral or involves a solitary kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580177 TI - Blood pressure and metabolic responses to hydrochlorothiazide, captopril, and the combination in black and white mild-to-moderate hypertensive patients. AB - Mild-to-moderate essential hypertensive patients (255) were assigned to receive hydrochlorothiazide 15 mg three times a day, captopril 25 mg three times a day, or both. A significant decline in blood pressure was seen in 84% of patients taking both agents, while 43% of those taking captopril and 64% of those taking hydrochlorothiazide showed a significant blood pressure response. Among white hypertensives receiving captopril alone, a normalization of blood pressure occurred in 46% and a significant reduction in 8% was observed which was significantly (p less than 0.05) higher than that observed in black subjects where only 31% showed a normalization of their pressure with captopril alone. With hydrochlorothiazide, 53% of blacks and 54% of whites showed normalization of their pressures. With the combination, over 80% of the patients in both racial groups demonstrated a normalization or significant reduction in blood pressure. With hydrochlorothiazide alone, significant (p less than 0.05) decreases in serum potassium, increases in uric acid, blood glucose, and blood cholesterol were seen. With captopril alone, no changes in any of these measurements were observed. When captopril was added to hydrochlorothiazide, a significant attenuation of the diuretic effect on potassium and uric acid was observed, and the significant change in blood sugar and cholesterol seen with the diuretic alone was prevented. These observations suggest that there are heterogeneous responses to hypertensive monotherapy based on race. Furthermore, it suggests that when a single therapeutic agent is not adequate in controlling blood pressure to the desired levels, the addition of either hydrochlorothiazide or captopril should produce a further reduction in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580178 TI - Effects of captopril, hydrochlorothiazide, and their combination on timed urinary excretions of water and solutes. AB - The effects of single doses of captopril 100 mg, hydrochlorothiazide 25 mg, and a combination of both on 24-h outputs of fluid and several solutes were compared in healthy volunteers. Thirteen subjects were studied in a metabolic ward under strictly controlled conditions. Single doses of placebo, captopril, hydrochlorothiazide, and a combination of captopril and hydrochlorothiazide were given double-blind in random order on 4 separate days. Urine was collected at regular intervals for 24 h after medication. The combination of captopril and hydrochlorothiazide and hydrochlorothiazide alone significantly increased the 24 h urinary outputs of Cl-, Na+, fluid, and K+ compared with placebo and also accelerated the corresponding urinary flows. Captopril did not change the 24-h urinary excretions of Cl-, Na+, fluid, and K+ significantly, though it advanced the time courses of their urinary flows. All medications significantly increased the 24-h renal outputs of Mg2+ and creatinine. Captopril significantly increased the 24-h urinary output of urate and advanced its urinary flow. Hydrochlorothiazide significantly decreased the output and retarded the flow. The combination of captopril and hydrochlorothiazide did not change the 24-h urinary output and retarded its flow. It is concluded that the renal excretory actions of captopril are more prolonged than the plasma levels of the drug would indicate. Captopril has diuretic effects which may vary in potency with aldosterone concentrations and uricosuric properties unrelated to aldosterone status. PMID- 2580179 TI - Captopril and hydrochlorothiazide in the fixed combination multicenter trial. AB - The severe side effects uncommonly seen with captopril seem to be associated with high doses and/or compromised patients. A very flat dose-response curve in high dosages and the expectation of fewer side effects made us combine low-dose captopril with enhanced stimulation of the renin-angiotensin-aldosterone (RAA) system. Methods used were as follows: (a) In 43 patients (25 female, 18 male, age 45 +/- 10) with inadequate lowering of blood pressure or side effects due to therapy, we started a combination therapy with the fixed combination of captopril 25 mg + hydrochlorothiazide (HCTZ) 25 mg twice a day after a washout phase of 14 days. If blood pressure was not lowered satisfactorily, we increased the dosage to a fixed combination of 50 mg captopril + 25 mg HCTZ for 6 months. (b) In 12 patients (eight male, four female, age 47 +/- 7) an initial high-dose treatment of captopril (3 X 50-3 X 150 mg, mean = 325 +/- 87 mg/day in combination with small doses of diuretics) was changed to low-dose captopril (2 X 50 mg, mean = 96 +/- 14 mg/day; dose reduction: 70%!) in a fixed combination with 25 mg HCTZ in each tablet. Results obtained were as follows: (a) Initial blood pressure values of 189/106 +/- 28/7 mm Hg fell to 160/84 +/- 23/12 mm Hg after 2 weeks. Systolic pressure decreased further to 146 +/- 20 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580180 TI - Differing dosages of captopril and hydrochlorothiazide in the treatment of hypertension: long-term effects metabolic values and intracellular electrolytes. AB - The effects of long-term treatment with differing dosages of captopril and hydrochlorothiazide in combination were evaluated in 22 hypertensive patients. There was no significant difference in antihypertensive efficacy between captopril 25 mg twice a day in combination with hydrochlorothiazide 25 mg once or twice daily and captopril 50 mg twice a day in the same combination. About 75% of patients achieved normotension. Once daily therapy with captopril 50 mg and hydrochlorothiazide 25 mg was effective in only 25% of patients. Long-term treatment (11 months) with captopril and hydrochlorothiazide did not cause any of the metabolic effects usually observed during diuretic administration. Intracellular (lymphocytic) Na+ was significantly reduced and intracellular K+ significantly increased by captopril and hydrochlorothiazide, and this led to the normalization of the intracellular Na+:K+ ratio, which is abnormally high in essential hypertension. Our data suggest that the association of low doses of captopril and hydrochlorothiazide is highly effective, well tolerated, prevents the metabolic side effects of diuretics, and has favorable effects on intracellular ionic composition. PMID- 2580181 TI - Clinical effects of low-dose captopril plus a thiazide diuretic on mild to moderate essential hypertension: a multicenter double-blind comparison with propranolol. Captopril Research Group of Japan. AB - A total of 270 patients with mild to moderate essential hypertension were evaluated in a multicenter double-blind randomized study that compared the effect of captopril plus a thiazide diuretic with that of propranolol plus a diuretic. All patients were previously uncontrolled with diuretics alone. Following a 4 week placebo control period, during which diuretic was not withdrawn, the patients were treated either with 37.5-75 mg/day of captopril (n = 133) or with 60-120 mg/day of propranolol (n = 137) for 12 weeks, the diuretic being continued in both groups. Blood pressure in both groups was significantly reduced after 2 weeks of treatment. Reduction in systolic but not diastolic blood pressure after 10 and 12 weeks of treatment was significantly greater in the captopril group than in the propranolol group (p less than 0.05). Treatment was considered to be effective in 77% of the captopril patients and in 61% of the propranolol group. The difference was significant (p less than 0.05). Side effects occurred in 6 of the 133 patients (4.5%) treated with captopril and in 16 of the 137 patients (11.7%) treated with propranolol. The difference between the two groups was significant (p less than 0.05). There were few significant changes in laboratory data in either group. The serious side effects previously reported with higher doses of captopril were not observed. The results indicate that low-dose captopril plus a diuretic is more efficacious than propranolol plus a diuretic in mild to moderate essential hypertension previously uncontrolled with a diuretic alone. PMID- 2580182 TI - Captopril: contrasting effects of adding hydrochlorothiazide, propranolol, or nifedipine. AB - Because captopril alone does not control blood pressure in all patients with essential hypertension, studies were performed to assess the effect of sodium intake and of captopril combined with hydrochlorothiazide, propranolol, and nifedipine. Captopril given for 5 days to normotensive subjects having high, normal, and low sodium intakes reduced blood pressure the most in those on the lowest intake; the fall correlated with that in plasma angiotensin II. When 12 patients with moderate hypertension had hydrochlorothiazide added to captopril their blood pressure fell significantly. When propranolol was added to captopril, however, there was no further fall in blood pressure. When propranolol was added to captopril and a diuretic, pressures measured 4 and 6 h after the last dose of captopril showed reduced values compared with placebo; pressures measured 2 and 12 h after did not. Nifedipine added to captopril reduced blood pressure more than either drug alone. When renin and angiotensin are low, as they may be in essential hypertension, captopril is less effective; its effectiveness should increase if sodium is restricted. Both diuretics and nifedipine increase the effectiveness of captopril; propranolol does not, although it may prolong captopril's action. Experience in patients with resistant hypertension suggests that adding nifedipine to captopril may reduce the need for diuretics, while adding captopril to nifedipine may reduce the need for beta-blockers. PMID- 2580183 TI - Antihypertensive treatment using calcium antagonists in combination with captopril rather than diuretics. AB - The antihypertensive efficacy of combination therapy with the angiotensin converting enzyme inhibitor captopril and a diuretic or a calcium antagonist was compared in 16 patients with essential hypertension with a blood pressure of over 160/95 mm Hg having triple drug therapy. While monotherapy with a calcium antagonist--usually verapamil 500 mg/day or nitrendipine 70 mg/day--did not reduce diastolic blood pressure to greater than 95 mm Hg, this goal was achieved in 15 out of 16 patients with the combination of captopril (53 mg/day) and the calcium antagonists in the above dose (151 +/- 4/88 +/- 2 SEM mm Hg) and in 13 out of 16 patients with captopril (84 mg/day) and a diuretic (158 +/- 4/91 +/- 1 mm Hg). There was a direct relationship between intraindividual pressure responses to the two drug combinations (r = 0.88, p less than 0.001). Heart rate was similar and weight lower on the captopril-diuretic combination. Captopril's antihypertensive efficacy can be equally enhanced by calcium antagonists (without affecting renin long term) as by diuretics, which are thought to work by stimulating the renin-angiotensin system. The calcium antagonist-captopril combination may be of particular advantage in hypertensive patients who are otherwise difficult to treat. PMID- 2580184 TI - Effect of chronic nifedipine in patients inadequately controlled by a converting enzyme inhibitor and a diuretic. AB - Nifedipine, in a slow release preparation, was given at a mean daily dosage of 47 +/- 4 mg to 12 patients with severe hypertension in whom arterial pressure was not satisfactorily controlled (mean arterial pressure 132 +/- 4 4 mm Hg) by the combination of a converting enzyme inhibitor and a diuretic. The addition of nifedipine induced an appreciable decrease in mean arterial pressure of 31 +/- 5 mm Hg and of serum potassium and plasma aldosterone. After adequate control of hypertension and because of severe hypokalemia in some patients, discontinuation of the diuretic was attempted in 10 subjects. After 1.7 +/- 0.5 months of treatment by the converting enzyme inhibitor and nifedipine no change in arterial pressure occurred while serum potassium had returned to normal in most patients. These results show that nifedipine may be useful in patients with a residual rise of arterial pressure when treated by converting enzyme inhibitor plus diuretics; in such patients, however, the serum potassium concentration should be carefully monitored. In addition, our observations suggest that calcium blockers may be an effective alternative to diuretics in patients receiving a converting enzyme inhibitor. PMID- 2580186 TI - Testicular neoplasms in Hispanic brothers. AB - Two hispanic brothers developed nonconcordant testicular malignancies in an interval of 11 months. They represent the 36th report of familial testicular neoplasia. The problems deriving from poor patient compliance are documented. PMID- 2580185 TI - Captopril in hypertension; seven years later. AB - Captopril was first administered to hypertensive patients 7 years ago. The relatively high dosage employed and the severity of diseases in the patient population initially led to a high frequency of side effects. Subsequently, an increase in the time intervals for dose titration and the earlier addition of a diuretic have made it possible to reduce the daily dose, thus significantly improving the drug's safety profile without compromising its antihypertensive effect. In a worldwide postmarketing surveillance study of captopril, 6,737 hypertensive patients were enrolled, of whom 3,219 were treated for at least 1 year. Patients had a mean entry blood pressure of 183 (+/- 31)/111 (+/- 16) mm Hg while still receiving an average of 2.3 antihypertensive drugs. However, 10.3% were not receiving therapy before entering the study. 1,811 patients (29% of those for whom relevant data were available) had impaired renal function on entry (serum creatinine concentration greater than or equal to 1.6 mg/dl). The hypertension of 881 of the patients (13.1%) was classified as mild to moderate. By design, the types of patients, dosage schedules, and patient monitoring requirements were consistent with the recommendations of the manufacturer at the time the study was initiated. The results of the study showed that long-term antihypertensive efficacy was maintained with a mean captopril dose of approximately 150 mg/day, when used either as monotherapy or more frequently with a diuretic. This dosage was associated with satisfactory control of blood pressure and a considerable reduction in the 12 months' cumulative frequency of drug discontinuation because of adverse reactions (5.8%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580187 TI - Measurement of monoamines and their metabolites in the interstitial fluid of the gut. AB - Bundles of hollow dialysis fibers were surgically implanted into the submucosa of the stomach and intestine allowing collection of an interstitial fluid (ISF) dialysate. Measurement of monoamines and their metabolites in ISF was performed using high-performance liquid chromatography with electrochemical detection. The local concentration of L-5-hydroxy-tryptophan (5-HTP) in ISF from the antrum was determined in conscious rats after intraperitoneal loading with 5-HTP. The metabolite was similarly evaluated after the administration of levodopa (L-DOPA). Validation of ISF dialysis as a method for determining changes of biogenic amine concentration in the extracellular fluid was determined for the antrum, duodenum, and colon in dogs after the oral or subcutaneous administration of 5-HTP as a precursor of serotonin and 5-hydroxyindole acetyl acetic acid. The proposed procedure provides a novel approach in pharmacologic studies, where a direct correlation between the distribution of a drug and its metabolites (pharmacokinetics) and their effects (pharmacodynamics) has to be measured. PMID- 2580188 TI - 14th annual UCLA symposia. March 9-April 4, 1985. Abstracts. PMID- 2580189 TI - 14th annual UCLA symposium. Abstracts: Sequence specificity in transcription and translation. PMID- 2580191 TI - Slow axoplasmic transport: a fiction? AB - Ribosomes have not been observed in axoplasm. This had led to the notions that the perikaryon is the only source of neuronal proteins and that the axoplasm is supplied by a (slow) transport mechanism. However, we question these two notions because they are unable to give an account of real neurones in accordance with the body of biological knowledge. We point out, for example, that the synthetic rate of perikarya or the life span of axoplasmic proteins should be beyond known ranges for animal cells and that a uniform axon is unlikely to result if it is fed from one end. We propose an alternative view for the maintenance of the axon which accepts the controversial idea of axoplasmic synthesis of proteins; as a result, the slow transport becomes unnecessary. Our view gives a qualitative account of the observations dealing with the maintenance of the axoplasm. To account for the phenomenology in a more quantitative fashion, a computer simulation was carried out where the equations of the program provided only for axoplasmic synthesis of proteins; the set of curves retrieved were in good agreement with experimental findings believed so far to support the notion of slow transport. In conclusion, we think that the notion of "slow axoplasmic transport" has been a misinterpretation of good observations because the frame of reference was incomplete in not providing for axoplasmic synthesis of proteins. PMID- 2580190 TI - Solvent effects in ionic transport through transmembrane protein channels. AB - Ion transport through a gramicidin A like channel in the presence of solvent molecules with van der Waals parameters of water has been studied by means of the molecular dynamics simulation technique. It was found that the presence of solvent molecules in the channel has a tendency to equalize the effective masses of the ions through "association" thus giving the experimentally found ion selectivity to the gramicidin A channel. PMID- 2580192 TI - A modified, prefixed, Golgi-rapid technique for the cephalopod retina. AB - A quick and simple method for Golgi staining of neurons and glia in the cephalopod retina is described. The main difference between this method and other Golgi-rapid protocols is that tissue is placed in sachets constructed from dialysis membrane prior to chromation and impregnation. This greatly reduces the amount of surface deposition of silver chromate and can reduce the number of elements impregnated. Together these effects produce improved Golgi staining of the cephalopod retina. Given some modifications to the osmolarity of the solutions employed, the method should be applicable to other, non-cephalopod tissues where superficial structures are obscured by surface precipitation, or neurons are arranged in thin sheets of tissue. The method employs prefixation of tissue in a fixative suitable for light or electron microscopy. PMID- 2580193 TI - Axoplasmic transport of substances in motoneuronal axons of the spinal cord in old age. AB - Seven to eight microliters of aqueous solution of L-[14C]Leucine (spec. act. 339 mCi/mmol) were introduced in the zone of ventral horn (L5-L6) of the spinal cord of adult (8-12 months) and old (26-28 months) rats. The radioactivity of various parts of the corresponding ventral roots was measured 1-2.5 h thereafter. Labelled substances (including protein) were found to migrate with fast flow in adult rats at the rate of 408 +/- 10.9 and 380 +/- 22 mm/24 h, respectively, as compared with 217 +/- 11.3 and 200 +/- 40 mm/24 h in old rats. The axoplasmic flow slows down in old rats with the increase of distance from the neuronal body. Uncoupling of oxidation and phosphorylation by the administration of 2,4 dinitrophenol, inhibition of glycolysis with NaF, hypoxemia produce more marked deceleration of axoplasmic flow in old rats, while small doses of NaF accelerate the flow, which correlates with the rise of cAMP in ventral roots. Sex steroids accelerate significantly the rate of axoplasmic flow. There is a marked increase in the rate due to the administration of estradiol dipropionate in old rats and due to testosterone propionate in adult animals. Changes in resting membrane potential and direct excitability thresholds of some muscles following colchicine blockade of axoplasmic transport are less marked in old rats that evidences for the weakening of neurotrophic control in old age. PMID- 2580194 TI - [Circadian rhythm of ionic calcium. Influence of specimen handling on serum levels]. PMID- 2580196 TI - [The barley cell or mastocyte: cellular and molecular biology]. PMID- 2580195 TI - [Usefulness of potassium permanganate staining in the classification of systemic amyloidoses]. PMID- 2580198 TI - [Cancer pain resistant to analgesics. New research findings can partially explain unsatisfactory effects of analgesics]. PMID- 2580197 TI - [Long-term follow-up of low birth weight infants shows a very low number of handicaps]. PMID- 2580199 TI - Does chorionic villus sampling cause fetomaternal haemorrhage? PMID- 2580201 TI - Ageing in Down's syndrome. PMID- 2580202 TI - Inosine pranobex in mucocutaneous herpes. PMID- 2580200 TI - Diagnosis of the carpal tunnel syndrome. PMID- 2580203 TI - [Initial results of hyperthermia in palliative therapy of cancers in the ENT area]. AB - Preliminary results of an interdisciplinary study, conducted to investigate the efficacy of combined local hyperthermia and radiation/chemotherapy on carcinoma of head and neck, are reported. Upto now, eleven patients with recurrent squamous cell carcinoma of head and neck were treated, all of them had loco-regional recurrence, and 2 distant metastases in addition. 7 patients were pretreated by surgery and radiotherapy, 4 by radiotherapy only, and 6 by chemotherapy. Microwave-induced low-dose local hyperthermia was combined with radiotherapy (telecobalt 1100-2400 rad) 6 cases (group A) and with chemotherapy (bleomycin and cis-platin/bleomycin) in 5 patients (group B). Intratumoural temperatures between 43 and 45 degrees C were achieved for at least 30 minutes. The loco-regional efficacy of hyperthermia was assessed. 10/11 patients with 13 tumours could be evaluated, Group A: 3 CR, 4 PR, Group B: 1 PR, 4 MR and 1 NC. PMID- 2580204 TI - Immunohistopathology of human olfactory epithelium, nerve and bulb. AB - The immunohistochemical characteristics of the human olfactory system were (OMP). OMP was detected in the olfactory receptor neurons and processes extending from the olfactory neuroepithelium to the olfactory bulb. The olfactory receptor cells located close to the epithelial surface also contained OMP. In severely degenerate regions, only a few OMP-containing cells were observed. Differences in OMP-staining intensity were noted among the olfactory receptor cells. The thick neuroepithelium. Proliferating olfactory neuroepithelium contained OMP reactive and nonreactive olfactory receptor cells. The presence of OMP reactive and nonreactive olfactory neurons indicates the coexistence of two functionally different phases of olfactory neurons. These findings suggest that continuous cell turnover is occurring in human olfactory neuroepithelium. PMID- 2580205 TI - Amphetamine stimulation of glutaminase is blocked by neuroleptics. AB - The ability of several classes of neuroleptics to inhibit the activity of phosphate-activated glutaminase was studied in several brain regions. These agents decreased glutaminase activity only in the amygdala. Amphetamine elevated glutaminase activity in this region. This stimulation was not blocked by (-) butaclamol, but was blocked by (+) butaclamol, haloperidol, chlorpromazine or clozapine. PMID- 2580206 TI - Histochemical changes of substance P, FRAP, serotonin and succinic dehydrogenase in the spinal cord of rats with adjuvant arthritis. AB - Various histochemical changes were found in spinal segments L4-L5 of rats with adjuvant arthritis, predominantly 30 days after inoculation. A slight to marked increase of substance P immunoreactivity occurred in laminae I, II and X. FRAP activity was enhanced in lamina II. Serotonin immunoreactivity was heavier in laminae I, VIII and IX in a few animals. The intensity of the histoenzymological reaction for succinic dehydrogenase increased in certain laminae VIII and X neurons. At day 15 of the disease the increase of substance P and FRAP activities was chiefly restricted to the medial portion of the superficial dorsal horn. There was a significant positive correlation between the scratching behaviour of arthritic rats and the substance P immunoreactivity in laminae X and I. If one accepts that scratching is pain-related, the data are consistent with a possible role of substance P in the chronic pain associated with adjuvant arthritis. They leave undetermined the significance of the other histochemical changes. PMID- 2580207 TI - In the search for new anticancer drugs. X. N,N; N',N'-bis(1,2-ethanediyl)-N''-(1 oxyl-2,2,6,6-tetramethyl- 4-piperidinylaminocarbonyl) phosphoric triamide--a new potential anticancer drug of high activity and low toxicity. AB - A new nitroxyl labeled TEPA derivative 5 containing the urea bridge between the phosphorus and the nitroxyl moiety, and the congeners containing the NOH and NH groups instead of the nitroxyl function were synthesized, and tested in vivo on CD2F1 mice for anticancer activity against P388 and L1210. The nitroxyl compound is more active than the reduced forms. The nitroxyl compound 5 elicits 170% ILS at 90 mg/kg after 30 days and 439% ILSmax after 60 days against P388, and has a higher therapeutic ratio (26.4) than the clinically used Thio-TEPA (2.75). The LD50 of 5 is 270 mg/kg, while that of Thio-TEPA is 18 mg/kg. Consequently, the nitroxyl compound 5 is a promising new anticancer drug. PMID- 2580208 TI - Interaction of steroidal alkaloid toxins with calcium channels in neuronal cell lines. AB - Depolarization with 50 mM K+ increased 45Ca2+ uptake into neuronal clonal cell lines NG108-15, N1E-115 and NH15-CA2. In each cell line this depolarization induced uptake was blocked by inorganic and organic blockers of voltage sensitive calcium channels. However, tetrodotoxin (10(-6) M) was ineffective. Moreover, in the presence of tetrodotoxin, neither batrachotoxin nor veratridine inhibited the depolarization-induced uptake. The novel dihydropyridine BAY K8644 enhanced depolarization-induced 45Ca2+ uptake into each cell line in a nitrendipine reversible fashion. In the presence of tetrodotoxin, the BAY K8644/50 mM K+ stimulated uptake could be partially inhibited by batrachotoxin (10(-6) M) and veratridine (5 X 10(-5) M). These effects were not altered by the presence of scorpion venom (1 microgram/ml). The results indicate that both batrachotoxin and veratridine can modulate the effects of dihydropyridines on the gating properties of voltage sensitive calcium channels. PMID- 2580209 TI - Synergism between lysophosphatidylserine and the phorbol ester tetradecanoylphorbolacetate in rat mast cells. AB - In rat peritoneal mast cells tetradecanoylphorbolacetate (TPA) induced a non cytotoxic histamine release in the absence of extracellular calcium. The addition of calcium prevented the TPA effect but micromolar concentrations of lysophosphatidylserine (lysoPS) converted the calcium-induced inhibition into a stimulation. Other lysophospholipids were inactive. In agreement with a mutual influence between lysoPS and TPA, minimal TPA concentrations enhanced the calcium dependent histamine release induced by lysoPS in the presence of nerve-growth factor. It is proposed that the calcium-dependent pathway promoted by lysoPS and the activation of protein kinase C by TPA act synergically to induce histamine release from mast cells. PMID- 2580210 TI - Murine monoclonal antibodies against "liver specific lipoprotein" (LSP) defining three antigenic sites which differ in tissue- and species-distribution and subcellular location. AB - The tissue and species cross-reactivity of three monoclonal antibodies against human liver-specific lipoprotein (LSP), as well as the subcellular locations of the respective target antigens, has been investigated using an enzyme-linked immunosorbent assay (ELISA). Antibody D6 was widely tissue cross-reactive and bound to human and rabbit but not rat, mouse or guinea pig tissues. This antibody bound to a particulate antigen localized in the microsomal fraction of rabbit liver, and distinct from enzyme markers for plasma membrane (5'-nucleotidase) and endoplasmic reticulum (glucose-6-phosphatase) in its sedimentation properties on sucrose density gradients. Antibody A9/63 bound to human liver and pancreas, but not kidney, spleen, adipose tissue, skeletal muscle, small intestine or heart, and also bound only to human and rabbit tissues. This antibody bound to a particulate antigen in pancreas, but a soluble antigen in liver. Antibody B20 bound to all tissues from all species tested, with the exception of guinea pig, and bound to particulate antigens in adipose tissue and pancreas but soluble antigens in other tissues (including liver). In addition to emphasizing the immunochemical complexity of LSP, these experiments demonstrate the suitability of monoclonal antibodies for analysis of its constituent antigens. PMID- 2580211 TI - Natural killer cells. PMID- 2580212 TI - [Preparation of patients with head and neck tumors for neutron teletherapy]. AB - The authors discuss some problems of preradiation preparation of patients with head and neck tumors for neutron teletherapy on the U-120 cyclotron of the Tomsk Polytechnical Institute in the Siberian Branch of the All-Union Cancer Research Center, AMS USSR. Some methods of the manufacture and employment technique of the fixing and forming devices for the optimization of neutron therapy are described. PMID- 2580213 TI - [3H-estradiol-17 beta in laboratory diagnosis]. AB - USSR made [3H]estradiol-17 beta was shown to be no inferior in quality to [3H]estradiol-17 beta produced by Amersham Int., Gr. Britain, for the determination of estrogen protein receptors in target tissues and for radioimmunoassay methods. PMID- 2580214 TI - Intragenic suppression of the temperature-sensitivity caused by a mutation in a gene controlling transcription (fit) in Escherichia coli. AB - Starting from a transcription-defective strain harbouring a temperature-sensitive mutation in the fit gene, a rifampicin-resistant, temperature-insensitive derivative has been isolated. Genetic analysis of this derivative demonstrated the presence of a second temperature-sensitive mutation in the same gene. The two mutations mutually suppress each other's phenotype. From cotransduction experiments, the fit gene has been mapped 0.32 min and 0.16 min clockwise from the aroD and pps loci, respectively, at 37.5 min on the linkage map. The mutants harbouring either or both of the fit mutations are defective in RNA synthesis at the non-permissive temperature. The fit gene product is suggested to function as an accessory transcription factor. PMID- 2580216 TI - Nonuniform red cell distribution in 20 to 100 micrometers bifurcations. AB - Several potentially important parameters influencing the disproportionate distribution of red cell flux and blood flow at a bifurcation are examined. These include parent vessel hematocrit, vessel diameter, suspending medium, cell distensibility, parent vessel blood flow rate, and local geometry. Measurements were performed on 20 to 100 micrometers bifurcations, fabricated such that all vessels of a given bifurcations have the same diameter. Suspensions of human red cells, hardened red cells, and mixtures of each in albumin-saline, Dextran 75, or plasma were flowed through the bifurcations and determinations of flow rates and discharge hematocrits were made for each of the channels. For the 20-micrometers channels, hematocrits were found using videophotometric techniques, and for the larger channels, hematocrits were measured directly from the exit streams. Flow rates for both were measured by meniscus travel downstream in small-diameter glass tubes. Within the limits of the present experiments, three of the variables proved to be of major importance: feed hematocrit, tube diameter, and flow-rate distribution. It was clearly demonstrated that red cell flux varies nonlinearly with fractional flow rate. Critical flow rates, at which all or none of the cells entered one of the branches, were found to vary with diameter and hematocrit as has been reported in other studies. The data were analyzed with a theoretical model which assumes that the parent vessel contains a core of uniformly distributed red cells surrounded by a marginal gap of suspending medium; in the parent vessel lumen, the flows to the two daughter branches were assumed to be separated by a chord. The marginal gap widths and tube hematocrits deduced from the data with this model are of reasonable magnitudes. PMID- 2580215 TI - Modulation of gene expression in Escherichia coli infected with single-stranded bacteriophage phi X174. AB - Synthesis of tryptophanase, D-serine deaminase and alkaline phosphatase in Escherichia coli C was repressed as the result of infection with the single stranded DNA bacteriophage phi X174. However, the degree of repression differed, the more catabolite-sensitive the operon was, the more severe was the repression. For the catabolite-sensitive enzymes it was found that cyclic adenosine 3'5' monophosphate (cyclic AMP or cAMP) was unable to release or reduce the phage induced inhibition. Experiments with amber mutants of phi X174 revealed that A, product of cistron A, was responsible for the inhibition. The cistron A product probably acted at the level of transcription. The possible role of A in the observed modulation of gene expression is discussed. PMID- 2580218 TI - The need for palliative care services in a general hospital. AB - A population census in a major Sydney teaching hospital showed that, at any one time, between 5% and 10% of inpatients were in the terminal stages of their disease and, thus, were in need of palliative care. These needs challenge conventional patterns of practice in large hospitals and illustrate the magnitude of the problems arising from the generally observed trend towards hospitalization of the dying. PMID- 2580217 TI - Permselectivity of the peritoneal membrane. AB - To investigate the osmotic barrier characteristics of the peritoneal membrane during conditions similar to peritoneal dialysis in man, yet transperitoneal fluid movement was measured in 20 cats following intraabdominal placement of isotonic saline and hypertonic solutions of NaCl, glucose, raffinose, and inulin. Also, isooncotic solutions of hemoglobin and albumin and two sulfated high molecular-weight dextrans were investigated. Transperitoneal fluid movement was measured by a volume recovery method. Oncotic pressures of test solutions and plasma were measured by osmometry. Peritoneal osmotic conductances were calculated from the rate of transperitoneal water movement and the difference in osmotic pressures between the test solution and isotonic saline. The average glucose osmotic conductance per unit body surface are was found to be 2.3 +/- 0.18 x 10(-3) ml . min-1 . mm Hg-1 . m-2, in good agreement with previous reports, and the glucose osmotic reflection coefficient (sigma) was estimated to be 0.02. All the osmotic conductances measured could be fitted to a peritoneal equivalent pore radius of approximately 6 nm according to current hydrodynamic theories. The peritoneal membrane filtration coefficient was estimated to be 0.12 ml . min-1 . mm Hg-1 . m-2, of which 0.5-1% was found to be due to transcellular water flow. In conclusion the results of this study indicate that the peritoneum is a highly selective membrane with restrictive properties comparable to those reported for continuous capillary beds. PMID- 2580219 TI - Morphine and palliative care. PMID- 2580221 TI - Structure and organization of genes for transfer ribonucleic acid in Bacillus subtilis. PMID- 2580223 TI - [Detection of intermediates of RNA reverse transcription for mobile dispersed MDG 1 and MDG 3 genes in Drosophila cells]. AB - Poly(A)+RNA-DNA hybrids complementary to mobile dispersed genetic elements MDG 1 and MDG 3 have been isolated from Drosophila melanogaster culture cells. DNA and RNA in these complexes are represented by perfect hybrids. Three types of single stranded DNA are detected in these hybrids: full-length DNA molecules of MDG containing one and two long terminal repeats (minus strand) and the long terminal repeat itself (plus strand). The results are consistent with the model of reverse transcriptional replication of MDG similar to that of retroviruses. PMID- 2580224 TI - [Analogs of natural nucleosides and their 5'-triphosphates carrying the amino group in 3'-position--highly effective inhibitors of replication, repair and transcription]. AB - The new type of DNA and RNA synthesis inhibitors is found. These compounds are active in synthesis, catalyzed by bacterial DNA and RNA polymerases and by eukaryotic DNA polymerases in vitro and in DNA replication in vivo. PMID- 2580222 TI - On the role of sulfolipids in mammalian metabolism. AB - Sulfolipids of mammalian origin include sulfosphingolipids, sulfoglycerolipids and steroid sulfates. Sulfosphingolipids (sulfogalactosylceramide) may be involved in sodium transport, interaction of opiates with their receptors, activation of oxygen radical generating system, and blood coagulation Factor XII. Sulfoglycerolipids and steroid sulfates may be involved in spermatogenesis and sperm capacitation. PMID- 2580225 TI - [Conformation characteristics of biopolymers]. AB - The 25 year efforts, concerning the problem of conformational peculiarities of nucleic acids and structure-dynamic properties of globular proteins, studied at the Laboratory of Isotopic Methods of the Institute of Molecular Biology of the USSR Academy of Sciences are reviewed. PMID- 2580226 TI - [The tRNA genes of pro- and eukaryotes. Organization, structure, transcription]. AB - The up-to-date data on cytoplasmic tRNA genes, their number and structure, as well as organization in the genome and transcription are reviewed. PMID- 2580227 TI - Isolation of a full-length mouse cDNA clone coding for an immunologically distinct p53 molecule. AB - Transfection of a cloned p53 gene into a p53 nonproducer Abelson murine leukemia virus-transformed cell line, L12, reconstituted p53 expression. The protein expressed in these cells was indistinguishable from that naturally expressed in p53 producer tumor cells. Conversely, p53 protein expressed in L12-derived clones that were established by transfection with a full-length p53 cDNA clone (pM8) exhibited a discrete immunological form. Immunoprecipitation of p53 with a panel of monoclonal anti-p53 antibodies showed that L12-derived clones that were transfected with the genomic p53 clone contained the same antigenic determinants as those found in the p53 protein expressed in tumor cells. These p53 proteins bound all monoclonal antibody types as well as the polyclonal anti-p53 tested. However, L12-derived clones established by transfection of the p53 cDNA clone (pM8) expressed a p53 protein that bound the RA3-2C2 and PAb200.47 anti-p53 monoclonal antibodies as well as polyclonal anti-p53 serum but totally lacked the antigenic receptor for the PAb122 and PAb421 monoclonal antibodies. The p53 proteins expressed by either genomic or cDNA p53 clones exhibited the same apparent molecular sizes and identical partial peptide maps. We suggest that transfection of the p53 gene induced expression of the entire group of the possible mRNA species, whereas cloned p53 cDNA (pM8) represented a single mRNA molecule that codes for a discrete species of p53 protein. PMID- 2580228 TI - Transcription unit of the rabbit beta 1 globin gene. AB - We have hybridized pulse-labeled nuclear transcripts to cloned DNA fragments from the rabbit beta-like globin genes to determine the developmental timing, extent, and asymmetry of their transcription. The fetal-adult gene beta 1 was transcribed in fetal liver but not embryonic nuclei, whereas genes beta 3 and beta 4, which encode embryonic globin polypeptides, were transcribed only in embryonic nuclei. This shows that the switch from embryonic to fetal-adult globin production in rabbits is accomplished primarily by differential transcription of the beta-like globin genes. Gene beta 1 was subdivided into M13 subclones and tested for hybridization to nascent RNA. The nucleotide sequence of the 3' flanking region of gene beta 1 was also determined for 2,447 base pairs past the polyadenylation [poly(A)] site. No transcripts were found 5' to the cap site, but asymmetric transcription of gene beta 1 proceeded at a high level through the gene and past the poly(A) addition site for 603 nucleotides. The level of transcription declined after this, gradually dropping through the next 568 nucleotides. No polymerases were found on a fragment that begins 1,707 nucleotides past the poly(A) site; this fragment was part of a segment of repetitive DNA. These data show that the transcription unit of gene beta 1 begins at or near the cap nucleotide and extends at least 1,171 but no more than 1,706 nucleotides past the poly(A) addition site. The DNA segment that precedes the region of declining transcription contained an inverted repeat and encoded a short RNA transcribed by RNA polymerase II from the strand opposite the beta 1 transcript. These two features may function to attenuate the transcription of gene beta 1. An inverted repeat and a potential polymerase II transcription unit were also found in the homologous segment 3' to the human beta-globin gene. A short DNA segment close to the 3' end of the beta 1 transcription unit was transcribed more actively than the surrounding DNA, and it contained sequences that match the consensus internal control region for RNA polymerase III. This DNA segment may contain a separate polymerase III transcription unit. A member of the D repeat family located 3' to gene beta 1 was not transcribed in its entirety coordinately with beta 1. PMID- 2580220 TI - Molecular basis of bacterial outer membrane permeability. PMID- 2580230 TI - Increased phosphorylation of tyrosine in vinculin does not occur upon transformation by some avian sarcoma viruses. AB - The level of phosphotyrosine in vinculin was determined in chicken embryo fibroblasts transformed by various strains of avian sarcoma virus. As previously reported (Sefton et al., Cell 24:165-174, 1981), vinculin was phosphorylated at tyrosine residues in most cultures examined, but the level varied greatly and no detectable change was found in cultures infected with Fujinami sarcoma virus or UR2 sarcoma virus. Regardless of the level of vinculin phosphorylation, the number of organized microfilament bundles was found to be decreased in all transformed cells. These results strongly suggest that tyrosine phosphorylation of vinculin is not an obligatory step in cell transformation by this class of oncogenes, nor is it correlated with the associated cytoskeletal disarray. PMID- 2580229 TI - Kinetochore components recognized by human autoantibodies are present on mononucleosomes. AB - We have developed a competitive enzyme-linked immunosorbent assay for solubilized kinetochore components, using human CREST (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, telangiectasia) scleroderma autoimmune antibodies specific for these kinetochore elements. Using this quantitative assay, we found interphase persistent or "pre-kinetochore" components in low- and moderately high-salt (375 mM salt) extracts of micrococcal nuclease-digested rat liver and chicken erythrocyte nuclei. The release of antigen activity from nuclei under these conditions has been correlated with loss of pre-kinetochore foci as determined by immunofluorescence microscopy. Combined biochemical and competition assay analysis of chicken erythrocyte nuclear extracts indicates that pre kinetochore components are tightly bound to chromatin of mononucleosome size. The conclusions based on competition assay data are supported by a direct binding assay, which confirms that antigens recognized by CREST sera are present on chromatin. These results raise the possibility that the kinetochore-specific chromosomal antigen(s) we have detected substitutes for "standard" mononucleosome components, such as histone H1. Furthermore, they suggest approaches to the isolation of kinetochore-specific DNA sequences from higher eucaryotes. PMID- 2580231 TI - Family of developmentally regulated, maternally expressed Drosophila RNA species detected by a v-myc probe. AB - Drosophila melanogaster genomic sequences that hybridize with v-myc have been reported (B.-Z. Shilo and R. A. Weinberg, Proc. Natl. Acad. Sci. U.S.A. 78:6789 6792, 1981). We have detected Drosophila RNA sequences that also hybridize with v myc. In an attempt to characterize these RNA sequences, we used v-myc hybridization probes to isolate Drosophila genomic segments. None of the Drosophila genomic or cDNA clones that we have isolated hybridize with the 3' exon of v-myc. Preliminary nucleotide sequence analyses have revealed sufficient homology to account for the observed hybridization between v-myc and the Drosophila clones but have failed to detect significant amino acid sequence homology. Thus is seems unlikely that the mRNA sequences or the genomic sequences that we have isolated by hybridization with v-myc represent homologs of the vertebrate myc gene. Despite the lack of structural homology between the cloned Drosophila sequences and v-myc, we have investigated the pattern of expression of those RNA species that hybridize with v-myc. Polyadenylic acid-containing transcripts of 2.7, 2.2, and 1.7 kilobases (kb) in embryos, pupae, adults, and Kc cells and an additional 1.4-kb transcript in adults were complementary to the Drosophila genomic clones and to v-myc. The 1.7- and 2.2-kb transcripts were localized on polyribosomes in Kc cells. The 1.7- and 2.2-kb transcripts were present after 45 min, 2 h, and 4 h of embryonic development, but by 16 h of development their levels had decreased by more than sixfold. During metamorphosis, two peaks of expression of the 1.7- and 2.2-kb transcripts were observed, at 6 and 72 h postpupariation. The 1.4-kb RNA species was first detected at 72 h postpupariation. In adults, the 1.7- and 2.2-kb transcripts were detected only in ovaries in females, whereas the 1.4-kb transcript was present in female nonovarian RNA and in males. These results suggest that the transcripts in early embryos are of maternal origin. PMID- 2580233 TI - Thyroid disease in pregnancy and the postpartum period. PMID- 2580232 TI - Endocrinology of pregnancy. PMID- 2580234 TI - Influence of the recB21 mutation of Escherichia coli K12 on prophage lambda induction. AB - The inactivation kinetics of the lambda repressor following bleomycin (BM), UV irradiation and nalidixic acid (NAL) treatments were studied in the recB21 mutant of E. coli K12. The results showed essentially normal induction by UV irradiation, delayed induction by BM and no induction by NAL. The results were compared with inactivation kinetics in lexA1 and recF143 mutants. PMID- 2580235 TI - Isolation of dermatophytes and other keratinophilic fungi from soil of Mussoorie (India). PMID- 2580236 TI - Purine metabolism in the intact sporozoites and merozoites of Eimeria tenella. AB - Intact Eimeria tenella sporozoites and merozoites did not incorporate radiolabeled formate or glycine into their purine nucleotides suggesting a lack of de novo purine synthesis. However, [U-14C]glucose was incorporated into the cellular purine and pyrimidine nucleotide pools of both forms probably via conversion to radiolabeled ribose-1-phosphate and/or 5'-phosphoribosyl-1-alpha pyrophosphate and the resulting action of various purine and pyrimidine salvage enzymes. Both forms of the parasite salvaged radiolabeled purine bases and nucleosides in a similar fashion. These purines were incorporated into ribonucleotides and into RNA and DNA. Adenine and inosine were transformed to hypoxanthine. Adenosine was converted to both inosine and hypoxanthine. Hypoxanthine and xanthine were not oxidized to uric acid but were metabolized to nucleotides. Guanosine was cleaved to guanine; guanine was deaminated to xanthine. The results demonstrate the presence of several purine salvage pathways. Purine phosphoribosylating and nucleoside phosphorylating activities as well as purine nucleoside cleaving and adenosine, adenine and guanine deaminating activities were evident. The metabolic evidence suggests the enzymes required to convert the newly formed nucleoside monophosphates to ATP and GTP were present also. PMID- 2580238 TI - In vitro determination of phagocytic indices of Candida berkhout species by rat peritoneal macrophages. AB - The aims of this investigation were to study and describe the behaviour of 13 different species of Candida, as compared with C. albicans, by means of phagocytosis assays in vitro. Tests were carried out with rat peritoneal macrophages in contact with quantified suspensions of live yeasts. Phagocytic indices, candidacidal activity and filamentation rat were tested microscopically after 3 h incubation at 37 degrees C. The phagocytic indices obtained allowed us to separate the fungi into four groups. Candida albicans and tropicalis belong to Group I; diddensii and shehatae, among others, belong to Group II; sake, krusei, viswanathii, etc., Group III; and C. glaebosa and haploid strains of Pichia ohmeri (C. guilliermondii var. membranaefaciens), Group IV. These data would suggest a possible correlation between pathogenesis and phagocytic indices. There were no evidences of any phagocytes ability to kill yeasts. Candidacidal activity was absent in the species assayed. Yeast lysis may have been observed if our assays would have taken longer than 3 h. PMID- 2580237 TI - Rapid diagnosis of intravascular catheter-associated infection by direct Gram staining of catheter segments. AB - We conducted a study to determine the usefulness of the Gram stain in the detection of intravascular catheter-associated infection. A total of 330 intravascular catheters were prospectively collected from adults and children suspected of having such an infection. Semiquantitative solid-agar cultures of the distal catheter tip were correlated with blood cultures. Catheter-associated bacteremia occurred in 34 per cent of cases in which catheter tips were colonized (greater than or equal to 15 colonies per agar plate). There were no cases of catheter-associated bacteremia in patients with uncolonized catheters. Immediately after culture, whole catheter segments were stained by the Gram technique. Gram-negative and gram-positive bacteria and yeast were easily identifiable under oil immersion (X 1000), located predominantly on external catheter surfaces. Any catheter with at least one organism per 20 oil-immersion fields was designated as positive by Gram stain, but the majority of the 41 positive catheters had much larger numbers of organisms. The Gram stain of the catheter tip was 100 per cent sensitive and 96.9 per cent specific for the detection of catheter-tip colonization, with positive and negative predictive values of 83.9 and 100 per cent, respectively. We conclude that a Gram stain of the distal catheter tip is a simple, inexpensive, and accurate test for the rapid diagnosis of intravascular catheter-associated infection. PMID- 2580239 TI - A hapten-specific chimaeric IgE antibody with human physiological effector function. AB - Immunoglobulin E (IgE) has a central role in allergic reactions although it rarely exceeds 5 micrograms ml-1 even in the serum of severely allergic individuals. Both mast cells and basophils possess receptors which bind the Fc portion of IgE with high affinity; crosslinking of membrane-bound IgE by allergen results in degranulation of the cell and release of a variety of pharmacologically active mediator including histamine. Myeloma IgE has been successfully used to block the skin sensitizing activity of allergic sera; however, human myeloma IgE is clearly in limited supply. The emergence of techniques allowing the stable introduction of immunoglobulin gene DNA into myeloma cells has allowed us to construct a mouse cell line that secretes a chimaeric IgE, lambda 1 antibody whose heavy chain is composed of a human C epsilon constant region fused to a mouse variable (VH) region. This chimaeric IgE is specific for the hapten 4-hydroxy-3-nitro-phenacetyl (NP) and can, when crosslinked by antigen, trigger the degranulation of human basophils. When not crosslinked, however, the chimaeric IgE can prevent the passive sensitization of these cells by sera from allergic subjects. PMID- 2580240 TI - Presynaptic neurones may contribute a unique glycoprotein to the extracellular matrix at the synapse. AB - As the extracellular matrix at the original site of a neuromuscular junction seems to play a major part in the specificity of synaptic regeneration, considerable attention has been paid to unique molecules localized to this region. Here we describe an extracellular matrix glycoprotein of the elasmobranch electric organ that is localized near the nerve endings. By immunological criteria, it is synthesized in the cell bodies, transported down the axons and is related to a glycoprotein in the synaptic vesicles of the neurones that innervate the electric organ. It is apparently specific for these neurones, as it cannot be detected elsewhere in the nervous system of the fish. Therefore, neurones seem to contribute unique extracellular matrix glycoproteins to the synaptic region. Synaptic vesicles could be involved in transporting these glycoproteins to or from the nerve terminal surface. PMID- 2580242 TI - The dihydropyridine derivative, Bay K 8644, enhances insulin secretion by isolated pancreatic islets. AB - The effects of the dihydropyridine derivative Bay K 8644 upon insulin secretion by perifused isolated mouse pancreatic islets were examined. At a non-stimulatory glucose concentration (5 mmol/l) Bay K 8644 (1 mumol/l) did not stimulate insulin release. However, the same drug concentration enhanced the insulin secretory responses to an intermediate (15 mmol/l) or high (30 mmol/l) glucose concentration by 80 or 90%, respectively. Bay K 8644 was half maximally effective at 0.1 mumol/l and maximally effective at 1 mumol/l. The results are compatible with the view that voltage-dependent calcium channels are essential for stimulus secretion coupling in pancreatic B-cells. PMID- 2580241 TI - Functional modifications of cytotoxic T-lymphocyte T200 glycoprotein recognized by monoclonal antibodies. AB - Plasma membrane glycoproteins of cytotoxic T lymphocytes (CTLs) are involved in the binding to and subsequent destruction of appropriate target cells. The electrophoretic profile of surface proteins of mature CTLs, particularly those of high relative molecular mass (Mr), is markedly different from that of naive peripheral T cells or non-cytolytic T cells, suggesting the possible involvement of these molecules in the activation of CTLs and/or in the lytic process itself. By generating monoclonal antibodies to cell-surface proteins of CTL clones, we have now detected CTL-specific modifications in one of these high-Mr membrane proteins, T200. Although forms of T200 are found on a wide variety of cell types, the neoantigenic determinants recognized by our antibodies are present exclusively on activated T cells and in high concentrations only on CTLs. Furthermore, the expression of the modifications recognized by our antibodies is influenced by soluble factors and also seems to have functional significance, as monoclonal antibodies specific for these novel epitopes block cytolytic activity. PMID- 2580243 TI - [Amylase isoenzymes as an aid in the diagnosis of pancreatic pseudocysts]. PMID- 2580244 TI - [Medical indication for heroin provision in Amsterdam]. PMID- 2580245 TI - Partial purification and characterization of tumor associated antigen in cervical carcinoma. AB - An identical component of tumor associated antigen (TAA) was detected in all clinical stages of the carcinoma of cervix (CaCx), in both premenopausal and postmenopausal patients, using heterologous antisera against the cancer tissues by immunodiffusion and immunoelectrophoretic tests. The TAA appeared to be cross reacting specifically with carcinoma of other gynecological organs. A second TAA component was observed to be present only in CaCx, Stage II of premenopausal patients. The TAA component of CaCx common for all clinical stages, irrespective of climacteric states, was partially purified by subjecting postmeno CaCx, Stage II to gel filtration on Sephadex G-200. The antigen was found to be glycoprotein in nature, enzyme sensitive, highly thermostable and antigenically active at a pH range of 2.0-10.7. The approximate molecular weight of the component was found to be 67 000. PMID- 2580246 TI - Value of human chorionic gonadotropin measurements in blood as a pregnancy test in women on maintenance hemodialysis. AB - Human chorionic gonadotropin (hCG beta) values were determined in the blood of 19 women and 4 men on maintenance hemodialysis. Blood samples were taken 3 times at an interval of 1 week. Measurements were done by an hCG beta RIA kit (Serono). The median hCG beta values were 9 mIU/ml (range 0-116) in 7 menstruating women, 6 (0-25) in 11 postmenopausal women and 0 (0-7) in 4 men. There was no statistically significant difference between the 3 groups. The median hCG beta values in all 3 groups were below the upper normal limit. However, the individual measurements varied considerably with elevation in 32% of 52 measured values (10 fold elevation in 2 cases). We conclude that in the blood of non-pregnant women on chronic hemodialysis, elevated hCG beta values can be found, erroneously indicating an intact pregnancy of 3-5 weeks duration or a nonintact pregnancy (e.g. impending abortion, extrauterine gravidity). PMID- 2580247 TI - Dialysis-induced cardiac arrhythmias: fact or fiction? Importance of preexisting cardiac disease in the induction of arrhythmias during renal replacement therapy. AB - Frequency and grade of premature ventricular depolarizations were assessed in 10 patients on maintenance renal replacement therapy. All medication was withdrawn prior to the study. Each patient was treated sequentially by 8 different methods [acetate and bicarbonate hemodialysis (HD), hemofiltration, hemodiafiltration, ultrafiltration, use of 5 different membranes]. Despite marked changes in serum electrolyte concentrations there was no difference in frequency or grade of premature ventricular beats between the periods before, during, and after renal replacement therapy. Comparison of the 8 methods tested revealed no superiority of 1 method during the observation period of 192 h for each patient. In a second group of 8 patients with confirmed coronary artery disease, acetate HD had no effect on grade and frequency of ventricular arrhythmias, although arrhythmias occurred more often (p less than 0.05) and were more dangerous. We therefore conclude that the incidence of ventricular arrhythmias is primarily dependant on the presence of preexisting coronary artery disease and that HD or related methods do not increase the risk of ventricular ectopies in patients without digitalis medication. PMID- 2580248 TI - Effect of hypothyroidism on the labeling of the various RNA species in developing rat brain. AB - The effect of hypothyroidism on the vitro incorporation of [3H]uridine into different RNA species in tissue slices of rat cerebral hemispheres at 5, 10, 15, and 21 days of age has been investigated. Gel electrophoresis analysis of total, nuclear and microsomal RNA was also accomplished. The results obtained indicate that RNA labeling is differently influenced by hypothyroidism at the various ages examined. RNA labeling is not significantly affected at 5 days of age while at later ages and especially at 21 days it is higher in hypothyroid rats compared to the controls. Moreover distinct differences at the various ages in the transport of newly synthesized RNA from the nucleus to the cytoplasm in the two groups of animals were found. These results are in agreement with the hypothesis that thyroid hormone deficiency causes a delay of the processes of cell proliferation and differentiation in developing rat brain. PMID- 2580249 TI - Comparison of the effects of benzodiazepines and other anticonvulsant drugs on synthesis and utilization of 5-HT in mouse brain. AB - Acute administration of clonazepam (0.5-8.0 mg/kg, i.p.), diazepam (2-32 mg/kg, i.p.), chlordiazepoxide (1-40 mg/kg, i.p.) or diphenylhydantoin (5-320 mg/kg, i.p.), caused a dose-related elevation of the concentrations of, 5 hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan in whole mouse brain. Carbamazepine (5-100 mg/kg, i.p.), and phenobarbitone (10-80 mg/kg, i.p.) raised the concentrations of 5-HT and 5-HIAA in the brain, whereas flurazepam (5-80 mg/kg, i.p.) only elevated the level of 5-HIAA. After administration of L[G-3H]tryptophan (25 microCi, s.c.), clonazepam (4 mg/kg), diazepam (32 mg/kg, i.p.), chlordiazepoxide (40 mg/kg) or diphenylhydantoin (40 mg/kg), but not carbamazepine (50 mg/kg), flurazepam (40 mg/kg) or phenobarbitone (80 mg/kg), increased the content of labelled tryptophan in brain. However, administration of drugs did not alter the incorporation of the label into [3H]5 HT, suggesting that the synthesis of 5-HT was unaffected. When incorporation of [3H]tryptophan into [3H]5-HT was complete and the pool of labelled 5-HT was decreasing, clonazepam, diazepam, chlordiazepoxide and diphenylhydantoin elevated the content of [3H]5-HT in brain. Flurazepam, phenobarbitone and carbamazepine were without apparent effect. Calculation of the rate of utilization of 5-HT (Km) showed that all drugs, apart from flurazepam, reduced the utilization of 5-HT. Using the rate of disappearance of 5-HT after inhibition of tryptophan hydroxylase by p-chlorophenylalanine (PCPA), all drugs, except flurazepam, diphenylhydantoin and phenobarbitone, decreased the utilization of 5-HT. The major action of the anticonvulsant drugs on the function of 5-HT in brain appears to be a decrease in the utilization of 5-HT without altering synthesis. PMID- 2580250 TI - Evidence on the retrograde neurotoxicity of doxorubicin. AB - Doxorubicin, a fluorescent retrograde neurotoxin, killed neurons in the ventral tegmentum and thalamus that were afferent to the injection site in the caudate putamen. The neurotoxic effects in the ventral tegmentum and thalamus were prevented by a large coronal knife cut caudal to the injection site in the striatum, suggesting that retrograde transport of doxorubicin is necessary for the death of afferent neurons. In the striatum the neurotoxic effects of doxorubicin 14 days post-injection were quantitatively much greater on afferent neurons (as assessed by a 72% drop in dopamine levels) than on local striatal perikarya (as evidenced by the small 22% drop in the activity of glutamic acid decarboxylase). Doxorubicin may be a useful tool for selectively destroying, by way of retrograde transport, neurons that are afferent to a site in the brain. PMID- 2580251 TI - The development of a programme for in vitro fertilisation in New Zealand. AB - The first seven months experience of a programme for in vitro fertilisation at National Women's Hospital in Auckland is described. Following a five month period of technique development, 36 women with tubal infertility were admitted to the programme from July 1983 to February 1984. A clinical pregnancy rate of 15% (6/41 laparoscopies) was achieved during this period. PMID- 2580252 TI - The malformed fetus: diagnosis and pregnancy management. PMID- 2580253 TI - Significance of raised maternal serum alpha-fetoprotein in singleton pregnancies with normally formed fetuses. AB - One hundred eighty-six pregnancies with elevated maternal serum alpha-fetoprotein (AFP) between 16 and 20 weeks' gestation, but with normally formed single fetuses, were analyzed retrospectively. In comparison with matched control subjects, there was an increased incidence of low birth weight, preterm delivery, intrauterine growth retardation, and other clinical complications, especially when maternal serum AFP was abnormally high on more than one occasion. These findings could not be explained by the occurrence of threatened abortion or the performance of amniocentesis. It is suggested that where maternal serum AFP screening for fetal neural tube defects is already established as a cost effective routine procedure, the additional recognition of some pregnancies at very high risk of other, perinatal complications is of practical value. However, maternal serum AFP testing in the second trimester cannot be recommended as a cost-effective screening method for detecting low birth weight infants, having a sensitivity in this series of only 11%. Many (33%) of the low birth weight infants detected in this way were very small (birth weights less than 1.5 kg); 73% of the predicted preterm births were very premature (before 34 weeks of gestation), and 72% of the identified growth-retarded infants were severely effected (weighing less than the fifth percentile for gestational age). PMID- 2580254 TI - Use of an immunoradiometric assay and a radioimmunoassay for the detection of free beta-human chorionic gonadotropin. AB - An immunoradiometric assay and a radioimmunoassay (RIA) were used to quantitate human chorionic gonadotropin (hCG) in the sera of ten pregnant women at term and of six women with gestational trophoblastic neoplasia. The two techniques show good correlation (Pearson correlation coefficient .96) in the assay of pregnancy serum. Because only the RIA, and not the immunoradiometric assay, measures the free beta-subunit of hCG, a comparison of the results obtained by the two immunoassay methods permits a semi-quantitative assessment of the free beta subunit. The numerical results may not reflect the actual concentration of free beta-subunit in that two different immunoassay methods are used. PMID- 2580255 TI - High-risk metastatic gestational trophoblastic disease. AB - The clinical course of 61 patients with high-risk metastatic gestational trophoblastic disease was reviewed. Currently, 34 patients (56%) are alive and in complete remission. The survival rate after full-term pregnancy was significantly worse than after any other type of antecedent pregnancy. Analyzing survival by individual high-risk criteria revealed significantly improved survival for those patients with elevated beta-human chorionic gonadotropin titer alone when compared with all other high-risk criteria. Fifty-eight percent of patients (14 of 24) primarily treated with alternating-sequential therapy consisting of methotrexate and actinomycin-D experienced a complete remission. Of those patients primarily treated with methotrexate, actinomycin-D, and cyclophosphamide, 63% (20 of 32) achieved a complete remission. Treatment with second-line chemotherapy was largely unsuccessful. Aggressive early treatment is warranted in this group of patients, using multiagent chemotherapy. A search for newer more effective regimens should continue. PMID- 2580256 TI - Adenoid cystic and adenoid basal carcinomas of the cervix. AB - Adenoid basal and adenoid cystic carcinomas of the cervix are uncommon and differ from each other in their histology, treatment, and prognosis. Whereas adenoid basal carcinoma is a slow-growing, locally invasive lesion amenable to simply hysterectomy, adenoid cystic carcinoma is an aggressive tumor associated with regional lymph node involvement and late pulmonary metastases. This study, based on the evaluation of nine cases of adenoid cystic and five cases of adenoid basal carcinoma of the cervix, reviews the literature and formulates a program for the management of these rare lesions. PMID- 2580257 TI - Making use of local resources. PMID- 2580258 TI - Innervation of the human pupillary sphincter muscle by nerve fibers immunoreactive to substance P. AB - Nerve fibers displaying substance P-like immunoreactivity (SPLI) were demonstrated in a whole human iris-ciliary body preparation using immunofluorescence technique. The SPLI nerves were mainly to be located in the posterior iris stroma beneath the pupillary sphincter muscle. PMID- 2580260 TI - Gustotoxicity of bleomycin. AB - 50 patients with advanced malignancy treated with bleomycin were assessed for taste abnormality. 5 (10%) cases were found to have some degree of taste impairment. Gustation sense returned to normal within 10-12 weeks following discontinuation of bleomycin therapy. The possible pathophysiology of gustotoxicity is discussed in the light of the available literature. PMID- 2580259 TI - Treatment of proliferative diabetic retinopathy. Long-term results of argon laser photocoagulation. AB - Panretinal photocoagulation (PRP) is the treatment of choice for proliferative diabetic retinopathy. Indications for treatment are the presence of disc new vessels or the presence of new vessels elsewhere with hemorrhage. Rubeosis iridis and retinal neovascularization undergo involution following panretinal photocoagulation. The long-term visual results are excellent excepting for eyes with diffuse diabetic retinal ischemia. Long-term follow-up and repeat photocoagulation as needed are advised. PMID- 2580261 TI - Reinnervation of skeletal muscle with a neuromuscular pedicle. AB - In the past decade the otolaryngologist has become interested in the problem of muscle reinnervation as it relates to laryngeal and facial paralysis. Although reinnervation by neuromuscular pedicle transfer has shown promising results in the laboratory and clinic, some investigators have had difficulty in achieving reliable results with this procedure. To further assess the technique's validity, we investigated the neuromuscular pedicle. This study utilized a strap muscle neuromuscular pedicle transfer to a contralateral strap muscle in the rabbit. The results were analyzed by the use of a number of independent measures, including electrical stimulation of the nerve, muscle contractibility, electromyography, enzyme histochemistry, reduced-silver staining for normal fibers, and the retrograde transport of the enzyme marker horseradish peroxidase. The physiologic and anatomic results demonstrated that morphologic and functional reinnervation of the experimentally isolated muscle by the transferred neuromuscular pedicle occurred. The most convincing data were produced by gross electrical stimulation, twitch and tetanic contraction, and horseradish peroxidase labeling. Electromyographic activity and other histologic findings supported the above conclusions. PMID- 2580264 TI - The measure of child. PMID- 2580262 TI - Neurotransmission and the experience of low back pain; no association between CSF monoamine metabolites and pain. AB - We have investigated the possible associations between the demographic, clinical and psychological characteristics of 80 patients with low back pain and the CSF levels of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3 methoxy-4-hydroxyphenylglycol (MHPG), the principal central nervous system metabolites of serotonin, dopamine and noradrenaline, and of tryptophan, the amino acid precursor of serotonin. Neither the clinical measures nor the psychological characteristics were significantly correlated with the CSF neurochemistry. Therefore the hypothesis about an intimate relationship between monoaminergic neurotransmission and the experience of chronic low back pain was not confirmed. Among the other factors studied, body height contributed most to the variance in both 5-HIAA and HVA concentrations; the levels of MHPG increased with age. PMID- 2580263 TI - Relationships between neurodevelopmental and educational findings in children aged 6 to 12 years. AB - Relationships between neurodevelopmental and educational findings were investigated in a clinic sample of 241 successive patients (aged 6 to 12 years) over a period of 6 months. Ratings of "definite," "possible," and "no problem" were compared between seven neurodevelopmental areas or three language functions and seven academic skills. Of the 40 associations tested in each of seven age groups, only one association (Boston Naming Test and reading comprehension) was statistically significant in a majority of the ages tested. Of the 280 comparisons (40 associations X seven age groups), only 37 (13%) were significant at P less than or equal to .05. The findings of this study do not support the use of the neurodevelopmental and educational measures employed in diagnosis of specific learning disabilities in a referred population. Health care professionals, however, may find neurodevelopmental assessment useful as a format for systematic observations of the child with performance disabilities. PMID- 2580265 TI - Cognition and states of consciousness: the necessity for empirical study of ordinary and nonordinary consciousness for contemporary cognitive psychology. AB - Recent criticisms of the place and function of "consciousness" in "cognitive science" are considered and rejected. Contrary to current orthodoxy subjective experience during abstract cognitive activity, especially when placed in its natural series with phenomenal accounts of so-called "altered states of consciousness," can provide unique and crucial evidence concerning just that core of "semantics" which eludes the automatized "syntax" of computer simulation. The "noetic" aspect of extreme altered states can be placed in relation to introspective descriptions of "insight." Various altered state features- synaesthesias, geometric/mandala imagery, reorganizations of "perceptual" dimensions and enhanced "self-reference"--can be taken as direct "exteriorizations" of abstract symbolic processes as discussed by Neisser, Geschwind, Mead, and Arnheim. A genuine cognitive psychology cannot continue to ignore the qualitative-experiential bases of symbolization. More specifically, the sense that insight just comes to us as if from "outside," its preliminary microgenetic processes masked, does not show the failure of introspective phenomenology but rather offers a unique and positive clue to the imaginal dialogic structure of higher mental processes. Thinking, as one phase of imaginal "conversation," must be "sent" from the phenomenal "other" to an attenuated, receptive phenomenal "self." A reconsideration of the Wurzburg controversy, adding closely related altered state phenomena to the transitional series between "impalpable awareness" and specific imagery, suggests that the normally masked processes underlying the "felt meaning" or "insight" state are most directly exteriorized as what Kluver termed "complex" or geometric-dynamic synaesthesias. Finally, a reinterpretation of classical introspectionism's "sensation" shows the "mechanism" by which the metaphorical/synaesthetic processes of cognition are generated. Titchener's "sensation" plays the crucial role in metaphor it so conspicuously lacked in functional perception. PMID- 2580266 TI - The facilitating effect of gangliosides on the electrogenic (Na+/K+) pump and on the resistance of the membrane potential to hypoxia in neuromuscular preparation. AB - The effects have been investigated of a mixture of gangliosides from beef brain cortex (GM1, GD1a, GD1b and GT1) either added to the bathing medium or injected intraperitoneally on muscle fibres and nerve terminals in mouse diaphragm. The electrogenic (Na+/K+) pump activity of muscle fibres enriched with sodium was increased by 38% after 2-h pretreatment with gangliosides (5 X 10(-8) mol X 1( 1]. Muscles from animals treated with gangliosides did not show the substantial depolarization of the resting membrane potential (RMP) in K+-free solution (6 h) shown by control muscles. Further, treatment with gangliosides slowed the changes in muscle fibre RMP and frequency of the miniature end-plate potentials in oxygen deprived muscles. PMID- 2580267 TI - Three functions of sodium channels in the toad node of Ranvier are altered by trimethyloxonium ions. AB - Voltage-clamped nodes of Ranvier of the toad Xenopus laevis were treated with trimethyloxonium ions (TMO) which are known to methylate carboxyl groups. TMO did not affect potassium channels but the sodium system was modified in three ways: a) the current was reduced, b) channels were rendered insensitive to tetrodotoxin (TTX) and c) the inactivation of all channels, TTX-resistant or not, was slowed in a potential range between 50 and 110 mV. Steady-state inactivation, however, was not changed. Presence of 100 nM TTX during TMO treatment prevented the production of TTX-resistant channels but did not hinder current reduction and slowing of inactivation. The TTX-resistant sodium channels were blocked by protons and had normal relative permeabilities to alkali metal ions. Repeated application of TMO further decreased the current and increased the relative amount of TTX-resistant channels; the slowing of inactivation, however, was quantitatively terminated after the first TMO treatment. It is concluded that the sodium channel contains at least three TMO-modifiable groups, which probably are carboxyl groups. PMID- 2580268 TI - A voltage-dependent K+ channel controlling the membrane potential in frog oocytes. AB - Full-grown frog ovarian oocytes (Rana esculenta), were voltage clamped with a conventional two-microelectrode system. Depolarizations from a holding potential of--60 mV produced slowly developing outward currents. Two-step clamp experiments showed that, in Ringer's solution, this current has a reversal potential at about -84 mV. Substitution of either sodium or chloride with impermeant ions in the external solution did not alter significantly the activation of the current nor its reversal potential. Increasing the potassium ions concentration caused a shift on the reversal potential in the positive direction with a slope of about 48 mV per decade. The presence of TEA ions (50 mM) in the external solution partially reduced the current. It is concluded that the membrane of full-grown frog ovarian oocytes possesses voltage-dependent ionic channels permeated mainly by potassium. They appear to play an important role in the control of membrane potential. PMID- 2580270 TI - Force response to rapid and slow small amplitude length releases in isometrically contracting normal width and radially compressed trabeculae from rat heart. AB - The early transient force response to small amplitude ramp length release, applied at the plateau of calcium activated force development, was studied in normal width and radially compressed trabeculae from rat right ventricle. Force recovery immediately following "rapid" (5 ms ramp duration) release was less in compressed than in normal width muscle. Force recovery immediately following "slow" (ramp duration greater than 160 ms) release was virtually absent in both compressed and normal width muscle. The difference in force levels between the beginning and end of slow releases was small in normal width muscle; in compressed muscle a noticeable difference in force levels was seen. The rate of force recovery immediately following "rapid" release, as given by the rate constant obtained by fitting a single exponential equation to the force recovery vs time data, was not altered by compression. These results suggest that radial compression divides crossbridges into two distinct populations: one which cycles normally and another which cycles very slowly, if at all. PMID- 2580269 TI - The mechanism of action of Ba2+ and TEA on single Ca2+-activated K+ -channels in arterial and intestinal smooth muscle cell membranes. AB - The interaction of Ba2+ and TEA with Ca2+-activated K+ channels was studied in isolated membrane patches of cells from longitudinal jejunal smooth muscle of rabbit and from guinea-pig small mesenteric artery (100 micron external diameter). Ba2+ applied from the inside of the membrane did not reduce unit current, except at high concentrations, but channels failed to open for long periods (s). This effect became much stronger when the potential gradient was in a direction driving Ba2+ into the channel and was reduced by increasing K+ ion concentration on the outside of the membrane. These results are consistent with Ba2+ entering the open channel and blocking at a site most of the way through the channel bore. In contrast, TEA and procaine dose-dependently reduced unit current amplitude at all patch potentials and slightly increased mean open time. Their effects were not detectably voltage-dependent and could be explained by TEA and procaine blocking the open channel with a timecourse that was faster than the frequency response of the recording system. The lack of appreciable voltage dependence suggests that TEA and procaine bind to a site near to the inner mouth of the channel. PMID- 2580271 TI - Forskolin prolongs action potential duration and blocks potassium current in embryonic chick sensory neurons. AB - To determine if alterations in internal cyclic adenosine monophosphate (cAMP) play a role in modulation of voltage-dependent channels in embryonic chick sensory neurons in vitro, forskolin (a direct activator of adenylate cyclase) was tested on the cells. Forskolin, in concentrations between 1 and 100 microM, produced dose-dependent, reversible increases in action potential duration. This effect of forskolin was blocked by incubation of the neurons in 1 mM 2',5' dideoxyadenosine, an inhibitor of forskolin-induced activation of cyclase in other cells. This suggests that the increase in action potential duration is likely to be mediated by activation of adenylate cyclase. Cholera toxin, another cyclase activator, also increased action potential duration when applied to the sensory neurons in a concentration of 10 micrograms/ml. Forskolin applied to voltage-clamped neurons decreased a voltage-dependent outward current, a result consistent with its effect on the action potential. These effects of forskolin are mimicked by capsaicin, but are in marked contrast to those previously reported for norepinephrine on the action potential and membrane currents (Dunlap and Fischbach 1981). Furthermore, forskolin does not block (or attenuate) the effects of norepinephrine, suggesting that increases in adenylate cyclase activity are most likely not involved in norepinephrine's action on the calcium channel. PMID- 2580272 TI - Electron microprobe analysis of proximal tubule cellular Na, Cl and K element concentrations during acute mannitol-saline volume expansion in rats: evidence for inhibition of the Na pump. AB - It has previously been shown that during mannitol-saline volume expansion (VE) Na transport was inhibited 50% by harvested proximal tubular fluid without a change in paracellular shunt pathway permeability to Na. To determine whether this inhibition was due to changes in cellular entry step or an effect on the pump itself, intracellular element concentrations were measured by electron microprobe X-ray ranalysis in proximal tubular cells of control (non-expanded, NE) and VE rats. Nai, Cli and phosphorusi were increased (mean +/- S.E.) from 19.3 +/- 0.8 to 23.4 +/- 0.6, 15.8 +/- 0.4 to 21.3 +/- 0.4 and 124.3 +/- 2.6 to 138.0 +/- 1.8 mmol . kg-1 wet weight (P less than 0.001) respectively while Ki remained unchanged: 122.9 +/- 2.2 and 124.2 +/- 1.3 mmol . kg-1 wet weight. The increases in Nai and Cli were in excess of cell shrinkage produced by the hyperosmolal peritubular environment while the unchanged Ki in the face of cell shrinkage indicates and actual loss. It is concluded that mannitol-saline VE inhibits the Na pump producing a rise in Nai and a fall in Ki. PMID- 2580273 TI - Block of sodium currents by the calcium antagonist D600 in human heart cell segments. AB - The effects of micromolar concentrations of racemic D600 on the transmembrane inward sodium current (INa) were investigated in voltage clamped, intracellularly perfused, human heart cell segments. Extracellular D600 blocked INa in a 'voltage and rate-dependent' manner as shown by the enhanced INa depression with a reduction of the 'resting' transmembrane polarization (Vmo) and stimulation interval (SI). D600 action was manifested as a voltage-dependent slowing down of the Na+ channels' recovery kinetics after a pulsed excitation, with greater recovery times during longer depolarized states, excited or non-excited. This phenomenon seems linked to the improved control of the intracellular environment normally influencing channel activity, and to the increased ratio of 'non sarcolemmal' to 'sarcolemmal' cell membranes for this preparation. PMID- 2580274 TI - Report of the policy conference on pacemaker re-use sponsored by the North American Society of Pacing and Electrophysiology. PMID- 2580276 TI - The control of atrial contraction by ventriculo-atrial pacing in the dog with AV block. AB - Atrial contraction in dogs with atrioventricular (AV) block was controlled by multiple atrial stimuli delivered during ventricular diastole. Acute hemodynamic changes were assessed. At a ventricular rate of 60 bpm, the spontaneous atrial rate averaged 83, and atrial cannon waves were frequent. When the atria were given two stimuli at an interval of 500 ms during ventricular diastole, the cannon waves were eliminated completely, and a fall in mean central venous pressure and a rise in systemic blood pressure were found. At a pacing rate of 90 bpm, similar changes in the cannon waves, mean central venous pressure, and systemic blood pressure were found when two atrial stimuli followed ventricular stimulation. Ventriculo-atrial multiple pacing may be useful in both clinical and experimental AV block. PMID- 2580275 TI - Ventricular thrombosis during permanent endocardial pacing in a pediatric patient with hemorrheological disorders. AB - Thrombosis in the right atrium or ventricle is a rare complication of permanent endocardial pacing in adults. To the best of our knowledge, this complication has not been previously reported at all in the pediatric age group. We report on a case of a 7-year-old boy who had large left ventricular thrombi that occurred during permanent endocardial electrical stimulation. Subsequent pulmonary emboli complicated congestive heart failure in this patient. As a diagnostic approach, echocardiography and pulmonary perfusion scintigraphy were used. We comment on possible causes of this serious complication and suggest hemorrheological and platelet activation studies in patients with permanent endocardial pacing. PMID- 2580277 TI - Surgical removal of entrapped endocardial leads without using extracorporeal circulation. AB - Of 267 patients having a tined endocardial lead implanted from 1978 to December 1983, three (1.1%) developed pulse generator pocket infection. Proper treatment of this complication involves removal of the pulse generator, continued external pacing via the implanted lead, pocket drainage and administration of specific antibiotics until the infected area clears. In two patients, the electrode could not be removed by traction. A sternotomy was performed, the pericardium was opened, the endocardial electrode was located by palpation, and a purse string suture (PSS) was prepared around it on the right ventricular wall. A new myocardial electrode with its corresponding generator was then implanted to reestablish pacing. Through the PSS the myocardium was incised, the distal end of the endocardial lead was exteriorized and severed, and the PSS was tied. The remaining lead was withdrawn proximally and the surgical wounds were closed. The results of this procedure have been been excellent, allowing the removal of the entrapped leads, with continuous pacing and without the need for extracorporeal circulation. PMID- 2580278 TI - A comparison between conventional and basket transvenous electrodes. AB - Three transvenous electrodes, two of a conventional type and one in the shape of a wire basket, were compared. In order to make a valid comparison, the electrodes were all attached to the same kind of lead. The conventional large and small surface electrodes showed no difference in early complication rate. The wire basket electrode, however, had significantly fewer early complications than the others. This was true whether the patients underwent a two- or a one-step procedure, and whether the surgery was done by experienced or inexperienced pacemaker surgeons. When inserted by experienced surgeons in a one-step procedure, the wire basket electrodes had an early complication rate of only 1.2%. Since this unrefined electrode that allows tissue ingrowth for improved anchoring has shown such good results, it is likely that other electrodes that have been perfected, of a hollow or porous design, will also be advantageous to the patients and show good results. PMID- 2580279 TI - Activation of the right ventricular apical electrogram during ventricular tachycardia: suitability for synchronizing intracavitary cardioversion. AB - An intravascular catheter positioned in the right ventricular apex has been used for intracavitary cardioversion in patients with recurrent ventricular tachycardia. We examined the timing of the right ventricular apical electrogram during sinus rhythm and ventricular tachycardia (VT) in order to determine if this signal could be used to synchronize the delivery of a countershock. Sixty three distinct morphologies of VT were observed in 33 patients undergoing electrophysiologic testing with programmed stimulation. Regardless of VT morphology or site of origin, the bipolar right ventricular electrogram always occurred within the peripheral QRS complex during ventricular tachycardia. Relative timing occurred within the QRS ranging from the initial 13% of the QRS to the last 12%. When all episodes of VT were examined, the timing of the right ventricular electrogram did not correlate linearly with the peak of the ECG, but the right ventricular electrogram occurred within 60 ms of the peak ECG in 83% of episodes of ventricular tachycardia. In one case of arrhythmogenic right ventricular dysplasia, the right ventricular electrogram occurred 160 ms after the peak ECG in ventricular tachycardia, a time when delivery of a countershock may have precipitated ventricular fibrillation. Six of these patients underwent cardioversion utilizing an intracavitary catheter and external generator. Acceleration of VT, or conversion to ventricular fibrillation, occurred following two of 27 shocks (7.4%). The right ventricular electrogram occurred the latest within the QRS complex in the two patients who developed acceleration of the tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580280 TI - Bipolar tined polyurethane ventricular lead: a four-year experience. AB - With the advent of polyurethane as an insulating material for permanent pacemaker leads, concern has arisen over the integrity and long-term durability of polyurethane-insulated pacing leads. Specific concern has arisen over particular bipolar tined polyurethane ventricular leads. We have assessed our 4-year experience with this lead. This experience involves two groups of patients, those with leads manufactured before a certain date and those with leads manufactured at a later date. In the first group (judged to be at increased risk) the failure rate was 8.8%, and in the second group (judged not to be at increased risk) the rate was 3.9%. Lead failure occurred at an average of 17.5 months in the first group. Adequate follow-up on the second group is not available to determine whether or not the failure rate may eventually be as high as that in the early group. Actuarial analysis suggests that survivorship free of lead failure is probably not significantly different in the two groups. This experience points out the need for determining lead failure rates, identifying optimal lead design and configuration, and establishing a lead registry or mechanism by which the integrity of various pacing leads can be evaluated. PMID- 2580281 TI - Dual chamber pacemakers: upper rate behavior. AB - Upper rate management of a dual chamber pacemaker requires sensing of the atrium and limitation of ventricular response to desired levels. Limitation of ventricular rate response is accomplished by setting atrial channel refractoriness which consists of two separate and continuous intervals, the atrioventricular interval (AV interval) and the atrial refractory interval, after the ventricular pace or sense event (AR interval). A P-wave that falls within the total atrial refractory interval (TARI) remains unsensed and one that falls beyond the TARI is sensed. If the upper rate limit interval (URI) is programmed to equal the TARI, the upper rate limit will occur by development of sudden AV block. If the URI is of greater duration (lower allowed rate) than the TARI, the difference in interval between the two is the Wenckebach interval (WI) and is the duration of a response plateau, when the atrial coupling interval is less than the upper rate interval. All dual chamber timing cycles can be interpreted in terms of atrial refractoriness and upper rate limitation with consideration of the lower rate interval, and the ventricular refractory and blanking intervals. PMID- 2580282 TI - Externally activated antitachycardia pacemaker with noninvasive electrophysiologic re-testing capability. AB - An Omni Orthocor 234A special device pacemaker was implanted in nine patients for treatment of drug-resistant supraventricular tachycardia (three patients) or ventricular tachycardia (six patients). This device is activated using a special external unit, which delivers from six to 15 stimuli at preselected coupling intervals ranging from 195 to 500 ms. Serial noninvasive electrophysiology studies were performed either in the hospital or on an outpatient basis using the triggered mode, which can respond to programmed chest wall stimulation. Three patients with reciprocating supraventricular tachycardia were treated effectively by this device during an average follow-up of 2.2 years. Of the six patients with stable ventricular tachycardia amenable to pacemaker termination, only four remained successful during an average follow-up of 1.9 years. Such devices may find important use in serial noninvasive electrophysiologic testing during long term clinical follow-up. The present form of this device is inadequate for widespread application, but may be useful for highly selected individuals. PMID- 2580283 TI - Disseminated aspergillosis and pacemaker endocarditis. AB - Clinical and pathologic findings in a 65-year old woman with fever of unknown origin are described in this report. Generalized aspergillosis with endocarditis was demonstrated at autopsy. The patient had no recognized risk factors for the development of fungal infection. A functional transvenous pacemaker lead, inserted 2 years previously, was completely encased in a large infected thrombus and may have been the initial site of infection. Septicemia and endocarditis are rare but well-described complications of cardiac pacing, and should be considered in the differential diagnosis of fever of unknown origin in patients with pacemakers. PMID- 2580284 TI - Extraction of a chronically infected endocardial screw-in pacemaker lead by pigtail catheter and wire loop via the femoral vein. AB - A 71-year-old woman was admitted after partial removal of an infected pacemaker system. Septicemia and subclavian vein thrombosis were present. With combined use of a pigtail catheter and a wire loop originally developed for endoscopic polypectomy, the infected catheter was pulled into the inferior vena cava. Counterclockwise rotation of the pigtail catheter following its fixation to the electrode by the wire loop allowed removal of the tip of the endocardial screw-in electrode from the myocardium and its extraction. Open heart surgery was avoided and the source of chronic infection was removed. PMID- 2580285 TI - Unusual mechanism of PR interval variation and nonreentrant supraventricular tachycardia as manifestation of simultaneous anterograde fast and slow conduction through dual atrioventricular nodal pathways. AB - Noninvasive recordings in a 69-year-old woman showed two distinct PR intervals of about 0.21 and 0.58 s, suggestive of dual AV nodal conduction. Various unusual mechanisms of transition from short to long and from long to short conduction intervals and phenomena of concealed conduction were due to the presence of two functionally separated intranodal pathways. Refractoriness of the slow pathway was associated with bradycardia. Episodes of tachycardia exhibited a one-to-two relationship between P-waves and ventricular activations as a consequence of simultaneous anterograde fast and slow conduction leading to double ventricular responses to single P-waves. PMID- 2580287 TI - Unusual presentation of DDD pacemaker system malfunction. AB - A DDD pacemaker utilizing an atrial J electrode was implanted in a patient whose right atrial appendage had been removed 7 years prior during aortic valve replacement. Alternating QRS morphologies produced by pacemaker stimulus artifacts occurred as a consequence of atrial lead dislodgement. The screw-in atrial electrode has superior stability in patients with right atrial appendage removal; stability of the atrial J electrode cannot be obtained in such cases. PMID- 2580286 TI - Appropriate diagnostic studies for sinus node dysfunction. PMID- 2580289 TI - Stimarec report of November-December, 1984. PMID- 2580288 TI - Comparison of vitreous carbon and elgiloy transvenous ventricular pacing leads. AB - In a randomized prospective study of 150 patients, we compared two porous-tipped, finned leads, one with a vitreous carbon tip (surface area = 12 mm2) and the other with an Elgiloy tip (surface area = 8 mm2). We assessed the acute and chronic stimulation thresholds and the ease of implantation of the two leads. The acute current thresholds for the vitreous carbon and Elgiloy-tipped leads were 1.7 +/- 0.5 (+/- SD) mA vs. 1.1 +/- 0.4 mA (0.25 ms pulse width), 1.3 +/- 0.5 mA vs. 0.9 +/- 0.3 mA (0.5 ms), and 1.0 +/- 0.3 mA vs. 0.8 +/- 0.3 mA (0.75 ms), respectively (P less than 0.0005). Impedance at implantation was 473 +/- 121 ohms and 716 +/- 285 ohms (P less than 0.0005) for the carbon-tipped and Elgiloy tipped leads, respectively. The R-wave amplitudes were 10.2 +/- 5.1 volts and 6.8 +/- 3.0 volts, respectively (P less than 0.0005). Both leads were easy to implant and showed low stable chronic thresholds from 3 weeks after implantation, at which time the stimulation threshold was 1.9 +/- 1.0 volts vs. 1.5 +/- 0.6 volts with the implanted voltage-variable generators and 1.8 +/- 0.8 mA vs. 1.6 +/- 0.6 mA with the implanted current-variable generators. Reoperation for displacement was required for two of the 87 (2.3%) carbon-tipped and 2 of the 67 (3.2%) Elgiloy-tipped leads. There was no exit block nor any other lead-related complication. We conclude that both leads have similar and satisfactory performance. PMID- 2580290 TI - Performance of cardiac pacemaker pulse generators. PMID- 2580292 TI - [Chemical neurolysis in advanced neoplasms]. PMID- 2580291 TI - N-acetylprocainamide kinetics during intravenous infusions and subsequent oral doses in patients with coronary artery disease and ventricular arrhythmias. AB - The kinetics of N-acetylprocainamide (NAPA) were studied in 5 patients (all men, mean age = 62) with coronary artery disease and ventricular arrhythmias during loading infusions of 0.22-0.45 mg/kg/min, prolonged (19-48 hrs) intravenous infusions 2.5-5.2 mg/min, and in 4 of the patients, during subsequent oral doses 1.5-3 g every 8 hrs. Serum, concentrations of NAPA were determined by high performance liquid chromatography. The individual concentration-time profiles could, with one exception, be described by a two-compartment, open, kinetic model with apparent first-order elimination. The kinetic variables were: initial distribution volume (Vc) 0.20 +/- 0.11 l/kg (mean +/- SD); steady-state distribution volume (Vss) 1.58 +/- 0.55 l/kg; distributional clearance (Cle) 133 +/- 23 ml/(kg X hr); absorption rate constant (Ka) 0.354 +/- 0.173 hr-1; and fraction of dose reaching systemic circulation (F) 1.00 +/- 0.14. The data for one patient who had received increasing oral dosages of 1.5, 2, 2.5 and 3 g every 8 hours resulted in systematic underprediction of observed concentrations at the two highest oral dosing rates. This suggests the possibility of some degree of nonlinearity or time-dependent change in the kinetic behavior of NAPA. Only low concentrations of procainamide, less than 1 mg/L, were found at the end of the infusions. PMID- 2580293 TI - Histopathology of prostate carcinoma. Diagnosis and differential diagnosis. AB - The prognosis of prostate cancer depends largely on the degree of differentiation. Therefore the pathologist plays an important part in diagnosis and therapeutic decisions. There are three different growth patterns: glandular, cribriform, and solid-undifferentiated. In the glandular pattern, well and poorly differentiated forms are to be distinguished. Well differentiated adenocarcinomas are observed predominantly in benign nodular hyperplasia as incidental carcinomas. In case of differentiation from benign proliferations, the behaviour of the cellular nucleus--size, form, and characteristics of nucleolus--is decisive. Inflammatory stromal reaction is always absent. The growth pattern and degree of nuclear atypia determine the degree of malignancy to be demonstrated in a score. In clinically manifest carcinomas, pluriform patterns are prevailing. The lowest degree of differentiation of each case counts for the grading. In incidental carcinomas, the extension of the carcinoma has to be determined by the resection material. Here the nodular carcinoma represents a special form primarily located in the centre and obviously developing from a nodular hyperplasia. The differential diagnosis of prostatic cancer may cause great problems. Primary and secondary--postatrophic--hyperplasias may be similar to a glandular and cribriform carcinoma. Atypical hyperplasias of irregular nuclear pattern are present. Carcinoma in situ is not the proper term for such proliferations. Concerning rare types of prostate carcinomas, the urothelial carcinoma, the carcinoma with argentaffine cells, so-called endometrioid carcinomas, and squamous cell carcinomas are of importance. Following conservative, antiandrogen and radio-therapy characteristic regressive alterations can be observed in the prostate carcinoma. Response and resistance to therapy of the local tumor growth may be assessed during follow-up. A grading system is proposed for this purpose. Among all markers immunohistochemically demonstrable, only the presence of acid prostate phosphatase and prostate specific antigen is of practical diagnostic importance in prostate cancer up to now. PMID- 2580294 TI - Breast tumors with a solid and uniform carcinoid pattern. Ultrastructural and immunohistochemical study of two cases. AB - Two cases of breast tumors with a uniform solid carcinoid pattern and argyrophilic dense-core granules were analyzed by immunohistochemistry in order to compare their characteristics with known features of other carcinoid tumors and ordinary breast carcinomas. The tumors were positive for keratin-type intermediate filaments, neuron-specific enolase and alpha-chain of human chorion gonadotropin but negative for vimentin and S-100 protein. Laminin was found only in a rim between tumor cell islands and stroma but not among the cells. It is concluded that these tumors are histologically, ultrastructurally and immunohistochemically similar to other carcinoid tumors. The present results suggest that both breast carcinoids and carcinomas may have a common precursor in the mammary secretory unit. PMID- 2580295 TI - Benign prostatic hyperplasia. Evaluation, management, and operative indications. AB - Although signs and symptoms of benign prostatic hyperplasia are found in an estimated 90% of men by the age of 70, less than 10% are likely to require surgery. If symptoms are mild and findings on urinalysis negative, nothing further need be done except follow-up evaluation in six months. Many patients stabilize without any progression of disease. When treatment is necessary, there is at present no alternative to surgery. Transurethral resection is the preferred procedure. Reoperation is seldom necessary. PMID- 2580296 TI - [Ossifying bronchial carcinoid in childhood. Report of a clinical case]. PMID- 2580297 TI - [Role of chemotherapy in the treatment of cancer of the testis in adults]. AB - Owing to its considerable effectiveness, modern multiple chemotherapy ranks first in the treatment of non-seminoma metastatic tumours of the testis. Its side effects in short-term treatment are recognized and acceptable in view of the results obtained, but they remain imperfectly known in long-term treatments. Fort this reason, the present tendency in clinical stage I non-seminoma tumours is to reserve chemotherapy for patients who relapsed after orchidectomy. Advanced seminomas with or without high levels of human chorionic gonadotrophin (subunit beta) already benefit from chemotherapy, and this treatment is likely to be extended to less disseminated forms of cancer. Pure or predominant choriocarcinomas still respond poorly to the cytotoxic drugs at present available. PMID- 2580298 TI - Complete sequence of a gene encoding a human type I keratin: sequences homologous to enhancer elements in the regulatory region of the gene. AB - We report here the complete nucleotide sequence of a gene encoding the 50-kDa keratin expressed in abundance in human epidermal cells. According to its sequence, this gene has a single transcriptional initiation site and a single polyadenylylation signal. Nuclease S1 mapping of this gene with total human epidermal mRNA confirmed the presence of a single initiation site for the 50-kDa keratin gene. When the regulatory sequences 5' upstream from this gene were examined, three sequences that share significant homology with viral and immunoglobulin enhancer elements were found. In comparison, the sequence of the regulatory region of vimentin, a structurally similar intermediate filament gene, was highly divergent [Quax, W., Egberts, W. V., Hendriks, W., Quax-Jeuken, Y. & Bloemendal, H. (1983) Cell 35, 215-223]. This finding may provide a clue to understanding the molecular mechanisms underlying the widely varying levels of expression of different intermediate filament genes in different tissues. PMID- 2580299 TI - A monoclonal immunotoxin acting on the Na+ channel, with properties similar to those of a scorpion toxin. AB - We describe the properties of a monoclonal antibody against the Na+ channel. The antibody, 72.38, competitively inhibited (Ki = 1.5 X 10(-9) M) the binding of an 125I-labeled toxin from the Brazilian scorpion Tityus serrulatus (125I-TiTX gamma) to Na+ channels of rat brain membranes. No significant inhibition of binding of a number of other Na+ channel toxins was observed. The inhibition of 125I-TiTX gamma binding also was observed with the solubilized Na+ channel from rat brain membranes (Ki = 2 X 10(-9) M). Antibody 72.38 antagonized 125I-TiTX gamma binding to Na+ channels from different animal species (fish, avian, and mammalian) and from different tissues (electroplax, brain, heart, and muscle). Moreover, 72.38 has been used for immunofluorescence labeling of Na+ channels in rat sciatic nodes of Ranvier and cultured dorsal root ganglion cells. Electrophysiological experiments on rat muscle cells fully confirmed the similarity between TiTX gamma and 72.38 seen in binding experiments. Both produce slow oscillations of the membrane potential accompanied by bursts of action potentials which are due to a selective action on the Na+ channel. TiTX gamma and 72.38 are without effect on the ion selectivity of the Na+ channel, but they both drastically change the voltage-dependence of activation and inactivation of the Na+ channel. PMID- 2580300 TI - Ca2+ entry in squid axons during voltage-clamp pulses is mainly Na+/Ca2+ exchange. AB - Intact squid axons were injected with aequorin and bathed in 3 mM Ca seawater (a concentration close to that of squid blood). Sodium and potassium currents were pharmacologically blocked and repetitive voltage-clamp pulses of a duration of 1.5 ms were applied (to simulate the duration of an action potential) at amplitudes of +30 to +90 mV and at frequencies of 100/s. In a very fresh axon (low internal Na concentration) no detectable change in aequorin glow resulted from this treatment, whether the axons were in Na-containing or in Na-free seawater. In axons subjected to modest Na loading, repetitive voltage-clamp pulsing did not result in an increased aequorin glow when the pulses were delivered in Na seawater, whereas in Na-free seawater there was an easily measurable increase in aequorin light emission during repetitive pulsing. The increase in aequorin photons emitted per voltage-clamp pulse was e-fold for 22 mV of depolarization, and the process showed no signs of saturating at pulse amplitudes of +180 mV (i.e., at a membrane potential close to ECa). The aequorin light emission per voltage-clamp pulse increased linearly with pulse duration (at constant amplitude). PMID- 2580301 TI - Optical measurement of voltage-dependent Ca2+ influx in frog heart. AB - Sarcolemmal Ca2+ movements in frog ventricular strips were measured by monitoring Ca2+ depletion from the extracellular space with an impermeant Ca indicator dye, antipyrylazo III. Ca2+ depletion was measured as a weighted average of light signals recorded simultaneously at three different wavelengths. This weighting procedure was designed to reduce the motion-induced light scattering and to enhance the Ca2+-related optical signals. Comparison of the time course of Ca2+ depletion signal with that of contraction showed that the rate of Ca2+ depletion was maximal immediately after the upstroke of the action potential but prior to the onset of tension. Peak Ca2+ depletion was reached toward the end of the action potential and amounted to a 10-50 microM decrease in the total extracellular Ca2+ concentration. The reaccumulation of extracellular Ca2+ seen after the action potential was 2-5 sec slower than the relaxation of tension. The rate of Ca2+ depletion had a bell-shaped voltage dependence and was enhanced by epinephrine, suggesting that Ca2+ influx occurred primarily through a slowly inactivating ionic channel. Ca2+ transport through the Na+-Ca2+ exchange system was not significantly altered in the presence of strophanthidin or with decrease of extracellular K+ concentration despite marked potentiation of tension by these agents. Ca2+ depletion measured at the end of a 1-sec clamp pulse had a voltage dependence noticeably different from that of the developed tension. This finding may suggest that a fraction of activator Ca2+ is released from membrane-bound Ca2+ pools in a voltage-dependent manner. Our results show that Ca2+ indicator dyes can be used not only to measure rapid changes in the extracellular Ca2+ concentration during contraction, but also to quantify the contribution of various sarcolemmal Ca2+ transport systems to the generation of tension in cardiac muscle. PMID- 2580302 TI - Structure of a gene for the human epidermal 67-kDa keratin. AB - We present the structure and nucleotide sequence of a gene encoding the human epidermal 67-kDa keratin. Three genomic clones were isolated from a lambda Charon 4A human genomic library by hybridization to a specific cDNA probe. One clone of 12.3 kilobase pairs was shown by R-loop, DNA sequence, and primer-extension analyses to encode an entire gene of about 6.25 kilobase pairs. Of eight identified introns, seven are located within the region that encodes the central coiled-coil alpha-helical domain of the protein. Except for one intron located at the end of the region encoding this domain, these do not delineate apparent structural subdomains. The positions of five of the introns exactly coincide with the positions of introns previously reported in the hamster gene for the intermediate filament protein vimentin [Quax, W., Egberts, W.V., Hendricks, W., Quax-Jeuken, Y. & Bloemandal, H. (1983) Cell 35, 215-233]. These findings suggest that the human 67-kDa keratin and vimentin genes arose from a common ancestral gene. PMID- 2580303 TI - Escherichia coli transcription termination factor rho has a two-domain structure in its activated form. AB - Limited tryptic digestion of Escherichia coli transcription termination factor rho [an RNA-dependent nucleoside triphosphatase (NTPase)] yields predominantly two fragments (f1 and f2) when the protein is bound to both poly(C) and ATP. The apparent molecular masses of the two fragments are 31 kDa for f1 and 15 kDa for f2, adding up to the molecular mass of the intact rho polypeptide chain (46 kDa). Sequence analysis of the amino termini demonstrates that f1 is derived from the amino-terminal portion of rho and that the trypsin cleavage that defines f2 occurs at lysine-283. These results suggest that, in the liganded (activated) form, the native rho protein monomer is organized into two distinct structural domains that are separable by a single proteolytic cleavage. The f1 fragment, purified from NaDodSO4/polyacrylamide gels and renatured, binds poly(C) but the f2 fragment does not; neither regains any ATPase activity. ATP- and polynucleotide-dependent changes in the rate of proteolysis and in the character of the fragments produced suggest that rho undergoes a series of conformational transitions as a consequence of RNA binding, NTP binding and NTP hydrolysis. The rate of loss of rho ATPase activity and of intact rho monomers is slower in the presence of adenosine 5'-[gamma-thio]triphosphate than in the presence of either ATP or ADP, indicating that the hydrolysis of ATP may result in different conformational effects than does the binding of this ligand. These findings are discussed within the context of recent models of rho-dependent transcription termination. PMID- 2580304 TI - Influenza viral (A/WSN/33) hemagglutinin is expressed and glycosylated in the yeast Saccharomyces cerevisiae. AB - Recombinant plasmids were constructed in which genes coding for either the entire or the signal-minus (amino acid residues 2-17 deleted) hemagglutinin (HA) of WSN influenza virus were placed under the control of the alcohol dehydrogenase I gene promoter of Saccharomyces cerevisiae. Both recombinant plasmids were shown to direct the synthesis of HA-specific polypeptides that were detected by immunoprecipitation with antiviral antibodies. The complete HA produced in yeast had an approximate Mr of 70,000 and was glycosylated, as determined by the endoglycosidase H sensitivity, and was bound to membrane. Therefore, the complete HA polypeptide possessing the signal sequence probably traversed the yeast secretory pathways. Signal-minus HA, on the other hand, had a lower molecular weight and was nonglycosylated. The specific binding of yeast HA with antiviral antibodies could be competitively inhibited by influenza viral HA, demonstrating that the HA produced in yeast contained antigenic determinants of the native viral HA. PMID- 2580305 TI - Spatial distribution of transcripts of the long repeated ETn sequence during early mouse embryogenesis. AB - RNA X DNA in situ hybridization revealed a high level of ETn ("early transposon") transcripts in the pluripotent cell lineage of the 3.5- to 7.5-day mouse embryo. Some extra-embryonic ectoderm derivatives also show a high level of ETn transcripts at these stages. Older embryos (8.5 days and later) have a uniform low level of ETn transcripts. PMID- 2580306 TI - Common haplotype dependency of high G gamma-globin gene expression and high Hb F levels in beta-thalassemia and sickle cell anemia patients. AB - We have studied 42 homozygous beta-thalassemia patients from Algeria and 34 sickle cell anemia patients from Senegal and Benin, determining the relationship between haplotypes, Hb F, and G gamma-globin/A gamma-globin ratios. Populations selected have a high frequency of haplotype homozygotes because of consanguinity (Algeria) and geographic homogeneity (West Africa). We find in beta-thalassemia patients, that haplotype IX in haplotypic homozygotes and heterozygotes, haplotype III in heterozygotes, and the Senegal haplotype in sickle cell anemia patients are all linked to high G gamma-globin expression. In addition, haplotypes IX and Senegal, but not haplotype III, have high Hb F levels. All of these haplotype have a common subhaplotype (+- ) in the gamma-globin gene region. In addition, haplotypes IX, III, and Senegalese sickle cell anemia patients exhibit hematological amelioration of their disease. Conversely, haplotypes I, V, and A in thalassemia patients, which also have a common subhaplotype (-----), and the Benin subhaplotype (--++-) in sickle cell anemia patients are all associated with low G gamma-globin and low Hb F levels. Low G gamma-globin expression in the adult is associated with two haplotypes that are not common between thalassemia and sickle cell anemia patients. We conclude that the determinant for high G gamma-globin expression is haplotype-linked to common and genetically dominant subhaplotypes in the two diseases. The total Hb F level, unlike the high G gamma globin expression, however, is linked to haplotypes but not to subhaplotypes, thus dissociating the two genetic effects. PMID- 2580307 TI - gamma-Aminobutyric acid receptor channels in adrenal chromaffin cells: a patch clamp study. AB - We have studied membrane channels activated by gamma-aminobutyric acid (GABA) in adrenal medullary chromaffin cells by using patch-clamp techniques. These channels share many properties with GABA-receptor channels in the central nervous system. They are chloride-selective, blocked by the GABA antagonist bicuculline, and reversibly desensitized at high GABA concentrations. The dose-response curve has a slope of 2 in the Hill plot, indicating a bimolecular binding reaction of GABA to the receptor. Single-channel currents display multiple conductance states as do glycine-activated chloride channels in mouse spinal neurons. Gating properties of GABA-activated channels, as described by a sequential model for agonist-activated channels, are similar to gating properties in central neurons. GABA-induced currents are potentiated by diazepam, indicating that anxiolytic drugs like the benzodiazepines might be involved in the regulation of anxiety states in the peripheral nervous system. PMID- 2580308 TI - Long-opening mode of gating of neuronal calcium channels and its promotion by the dihydropyridine calcium agonist Bay K 8644. AB - A large-conductance calcium channel in chicken dorsal root ganglion neurons was studied with patch-clamp recordings of unitary currents. In addition to the conventional pattern of Ca-channel gating previously described in neurons ("mode 1"), we observed a different form of gating behavior ("mode 2"). Unlike the brief (approximately equal to 1 ms) openings in mode 1, mode 2 openings tend to be longer (greater than 10 ms) and often outlast the test pulse. In mode 2, the probability of channel openness (P) is high at relatively negative potentials where P in mode 1 is low. Mode 2 activity appears much less often than mode 1 activity in the absence of drug. However, the balance is strongly shifted in favor of mode 2 by the dihydropyridine Ca agonist Bay K 8644, an effect that underlies a marked enhancement of Ca-channel activity. This is the first evidence for dihydropyridine control of neuronal Ca-channel function at the single-channel level. Sweeps showing mode 1 or mode 2 gating appeared interspersed with sweeps with no openings, during which the channel was unavailable for opening ("null mode" or "mode 0"). Two approaches showed that switching between all three modes occurred on a time scale of seconds: (i) channels tended to remain in the same mode from one sweep to the next, with pulses at 0.25 Hz; and (ii) steady depolarizations in Bay K 8644 produced clusters of mode 2 openings lasting several seconds. Changes in the rates of switching might be important in neurochemical modulation of Ca channels. Bay K 8644 and other dihydropyridine Ca agonists might be useful experimental tools for manipulating transmitter release, neurite extension, and other neuronal functions dependent on intracellular Ca. PMID- 2580310 TI - Cadmium-induced blockade of the cardiac fast Na channels in calf Purkinje fibres. AB - The fast transient inward current elicited by depolarizations above about -60 mV in calf Purkinje fibres was found to be depressed by Cd in concentrations less than 1 mM. The Cd-sensitive current, which strongly depended on external Na, was recorded in the presence of 2 mM MnCl2 and was blocked by TTX, indicating that a contamination from slow Ca-dependent currents could be discounted. The current reduction caused by Cd was also observed in nominally Ca-free solutions. The Cd induced depression of the fast Na current was not accompanied by changes in the current kinetic parameters, as revealed by comparing inactivation curves and peak current voltage relations at different Cd concentrations, and could be attributed to a voltage-independent channel blocking action. Half-blockade occurred at 0.182 +/- 0.06 mM (n = 4). Plots of peak current amplitude as a function of the Cd concentration showed that the cooperation of two Cd ions was required to block a single channel. PMID- 2580311 TI - The future of genetic amniocentesis. PMID- 2580309 TI - The all-or-none role of innervation in expression of apamin receptor and of apamin-sensitive Ca2+-activated K+ channel in mammalian skeletal muscle. AB - The long-lasting after-hyperpolarization(s) (AHP) that follows the action potential in rat myotubes differentiated in culture is due to Ca2+-activated K+ channels. These channels have the property to be specifically blocked by the bee venom toxin apamin at low concentrations. Apamin has been used in this work to analyze, by electrophysiological and biochemical techniques, the role of innervation in expression of these important channels. The main results are as follows: (i) Long-lasting AHP that follows the action potential in rat myotubes in culture disappears when myotubes are cocultured with nerve cells from the spinal cord under the conditions of in vitro innervation. (ii) Extensor digitorum longus muscles from adult rats have action potentials that are not followed by AHP but AHP are systematically recorded after muscle denervation and they are blocked by apamin. (iii) Specific 125I-labeled apamin binding is undetectable in innervated muscle fibers but it becomes detectable 2-4 days after muscle denervation to be maximal 10 days after denervation. (iv) Apamin receptors detected with 125I-labeled apamin are present at fetal stages with biochemical characteristics identical to those found in myotubes in culture. The receptor number decreases as maturation proceeds and 125I-labeled apamin receptors completely disappear after the first week of postnatal life, in parallel with the disappearance of multi-innervation. All these results taken together strongly suggest an all-or-none effect of innervation on the expression of apamin sensitive Ca2+-activated K+ channels. PMID- 2580312 TI - Interpreting AFP and AChE results in bloodstained amniotic fluid samples. PMID- 2580314 TI - Induction of neural-tube defects in nonhuman primates. PMID- 2580313 TI - Prenatal diagnosis of congenital nephrosis. PMID- 2580315 TI - Population and case-control surveillance in the search for environmental causes of birth defects. PMID- 2580316 TI - Population screening: report of a workshop. PMID- 2580317 TI - Determination of pepsinogen I in serum by radioimmunoassay. PMID- 2580318 TI - Enzyme linked immunosorbent assay of pepsinogen I. PMID- 2580319 TI - Comparative studies of prostaglandin E2, phenylisopropyladenosine, clonidine and propranolol on lipolysis stimulated by methylisobutylxanthine and isoprenaline in hamster fat cells. AB - The antilipolytic effects of prostaglandin E2 (PGE2), phenylisopropyladenosine (PIA), clonidine (alpha-2 adrenoceptor agonist) and propranolol (beta- adrenoceptor antagonist) on lipolysis stimulated by methylisobutylxanthine (MIX) (2 x 10(-4)M) and isoprenaline (5 x 10(-7)M) were compared in hamster fat cells. PGE2, PIA and clonidine inhibited markedly lipolysis stimulated by MIX, and slightly that stimulated by isoprenaline. Whilst propranolol inhibited markedly lipolysis stimulated by isoprenaline and slightly that stimulated by MIX. These results indicate that the inhibitory activity of PGE2, adenosine and alpha-2 adrenergic receptor stimulation depends upon the presence of MIX, whereas that of the beta-adrenoceptor blockade does not. PMID- 2580320 TI - Methyl xanthines enhance taste: evidence for modulation of taste by adenosine receptor. AB - The methyl xanthines (MX), theophylline, caffeine, and theobromine, are potent antagonists of adenosine receptors. Adaptation of the human tongue to methyl xanthines at concentrations ranging from 10(-5) M to 10(-2) M was found to potentiate taste. The artificial sweetener acesulfam-K, which has a bitter component, was potentiated the most by MX, i.e., approximately 100%. This increase in perceived intensity for acesulfam-K occurred at 10(-5) M MX, a concentration known to inhibit adenosine receptors but below that required to inhibit phosphodiesterase. Increasing the concentration of MX as high as 10(-2) M did not increase the degree of enhancement appreciably. Taste enhancement was found for NaCl and quinine hydrochloride as well. When 10(-5) M adenosine was added to the MX, the potentiation was reversed. The human results were confirmed by animal studies in which single unit extracellular recordings were made from the nucleus of the solitary tract. These results suggest that the inhibitory A1 adenosine receptor plays an important local role in taste perception. PMID- 2580321 TI - Serotonin turnover and supersensitivity after neonatal 5,7-dihydroxytryptamine. AB - Adult awake rats which received neonatal pargyline and 5,7-dihydroxytryptamine to severely reduce CNS serotonin terminals and perikarya have a reduced rate of accumulation of brain stem 5-hydroxytryptophan after Ro-44602. The rate of accumulation in the cerebral cortex and spinal cord were near normal when adult, even though serotonin and 5-hydroxyindoleacetic acid were sharply reduced in these regions. The respiratory response to 5-methoxy N,N-dimethyl-tryptamine was much more pronounced in pargyline-5,7-dihydroxytryptamine treated rats than in controls. If supersensitivity in serotonin receptors only develops in areas with decreased transmitter turnover, the site of action of serotonin agonists to depress respiration would seem to reside in the brain stem region. The results also suggest that compensatory changes in turnover do not develop to a similar degree in all CNS areas with altered serotonin content. PMID- 2580322 TI - Structure and expression of differentiation antigens on functional subclasses of primary sensory neurons. AB - Subpopulations of dorsal root ganglion neurons can be distinguished on the basis of their peripheral receptive properties, spinal terminal arbors and neuropeptide content. We have used monoclonal antibodies (MAbs) to define antigenic determinants on functional populations of DRG neurons projecting to the superficial dorsal horn of the spinal cord. Three MAbs recognize defined carbohydrate epitopes associated with lacto- and globo-series glycolipids that constitute the stage-specific embryonic antigens (SSEAs) 1, 3 and 4. SSEA-3 and SSEA-4 are present in the cytoplasm of about 10% of DRG neurons in adult rat. These neurons are distinct from those that contain substance P, somatostatin or the fluoride-resistant acid phosphatase enzyme, FRAP. SSEA-1 is present in a small percentage of DRG neurons. SSEAs are present on the surface of DRG neurons maintained in dissociated cell culture: 6% are SSEA-1+, 7% are SSEA-3+ and 10-15% are SSEA-4+. MAbs LD2, KH10, TC6 and TD10 identify epitopes expressed coincidently in 25% of small DRG neurons that project to lamina II of the dorsal horn. All somatostatin- but less than 1% of substance P-immunoreactive DRG neurons express these antigens. MAb LA4 labels a distinct population of small DRG neurons that also projects to lamina II. There is extensive overlap between LA4+ neurons and those that contain FRAP. Antigens recognized by these MAbs are expressed on the surface of 10-20% of DRG neurons in culture. Preliminary biochemical studies suggest that these antigens may be glycolipids. Molecules bearing carbohydrate differentiation antigens may be involved in the development and specification of sensory connections in the dorsal horn of the spinal cord. PMID- 2580323 TI - Peptide- and non-peptide-containing unmyelinated primary afferents: the parallel processing of nociceptive information. AB - Primary afferent C fibres can be subdivided into a number of subgroups on the basis of cytochemistry or receptor binding characteristics. Numerous peptides have been localized to dorsal root ganglia, yet these appear to be only found in approximately 50% of small perikarya. A large proportion of the remaining small cells do not contain peptides but are identifiable in rodents by their content of a fluoride resistant acid phosphatase. Attempts have been made to correlate particular biochemical types with particular receptive field profiles, with rather modest success. As an alternative we suggest, principally from an analysis of skin afferents, that peptide- and non-peptide-containing afferents are two distinct C fibre pathways innervating similar peripheral structures and conveying similar information, but to different areas within the dorsal horn. Morphological evidence also suggests that these two subsystems form either glomerular or simple synaptic arrangements in the dorsal horn. The significance of parallel pathways for the processing of nociceptive information is briefly discussed. PMID- 2580324 TI - Membrane changes in cells from myotonia patients. PMID- 2580326 TI - Wiggers Award lecture. Biochemical correlates of myocardial hypertrophy. PMID- 2580325 TI - Thermodynamic analysis of muscle ATPase mechanisms. PMID- 2580327 TI - Delayed neovascularization in free skin flap transfer to irradiated beds in rats. AB - A model for the study of neovascularization with a normal epigastric free flap set into an irradiated defect in the Fischer F344 rat is presented. In this model, both the administration of radiation and the flap transfer mimic the clinical situation. Significantly less tissue survives loss of the complete vascular pedicle at the second to fourth days following flap creation in rats with an irradiated bed. Later survival is not different from controls. Delayed neovascularization is proposed as the mechanism responsible for this effect during the period corresponding to the onset of the late phase of the response to skin radiation in rats. That neovascularization does occur, although delayed, suggests that the induced endarteritis may not be as important as previously suggested. PMID- 2580328 TI - Behavioral analysis of the effect of substance P injected into the ventral mesencephalon on investigatory and spontaneous motor behavior in the rat. AB - In the present experiments the behavioral response to substance P (SP) microinfusion into the ventral tegmental area (VTA), substantia nigra (SN), and sensorimotor cortex (CX) was investigated in detail. The experiments were carried out using an eight-hole box to measure exploratory behavior and a video monitor for the analysis of spontaneous motor behavior. When infused into the VTA, SP (0.125, 0.5, 3.0 micrograms) augmented the frequency and total duration of hole pokes, and tended to diminish the mean duration of hole-pokes. The strategy and organization of responses, as measured by the order of hole-visits and hole switching, were unchanged by SP and there was no indication of stereotypy, measured by the number of hole-pokes per hole-visit. The open-field analysis revealed a marked increase in locomotion and rearing, both in the periphery and center of the arena; grooming was decreased by SP. The behavioral profile following SN infusions of SP (3.0 micrograms) was similar to that elicited by VTA infusions, with the exception that center rearing was not enhanced. SP administration into cortex (3 micrograms) had no significant effect on any behavioral measures. It is hypothesized that SP infused into the ventral mesencephalon results in an enhancement of approach response tendencies, suggesting that endogenous SP in this region may regulate spontaneous behavior. The possibility of an interaction between SP and meso-telencephalic dopamine neurons is discussed. PMID- 2580330 TI - Interferons and the physician. PMID- 2580329 TI - Decrease in dopamine, its metabolites and noradrenaline in cerebrospinal fluid of schizophrenic patients after withdrawal of long-term neuroleptic treatment. AB - Dopamine (DA), homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), noradrenaline (NA), and 5-hydroxyindolacetic acid (5HIAA) were measured in cerebrospinal fluid (CSF) of 15 chronic schizophrenic patients before and 2 weeks after withdrawal of long-term neuroleptic treatment. Total neuroleptic-like activity in serum (NLA) was determined at the same times. Levels of DA and its metabolites (DOPAC and HVA) and NA were significantly reduced after the discontinuation of neuroleptic treatment. No change was observed in 5HIAA values. NLA was substantially reduced, but still remained detectable. The decrease in DA, DOPAC, and HVA all showed positive correlations with each other, and correlated negatively with NLA measured after 2 weeks. Our data implies that the decrease in DA turnover is the result of the discontinuance of DA receptor blockade, while the change in NA level is independent of it. PMID- 2580331 TI - Medical complications of bulimia: a prospective evaluation. AB - Recent increase in the identification and treatment of bulimia, an eating disorder characterised by excessive eating and often accompanied by some form of purging behaviour, has led to an interest in its proper medical evaluation. Although scattered reports describe a multitude of associated medical complications, their true incidence is not known. We describe our experience with 39 consecutive bulimic patients who underwent thorough medical evaluation. Serious disease was rarely encountered although a significant association was found between low body weight and hypokalaemia. Elevated serum amylase values were also noted in 15 of 24 patients (62 per cent). The potential utility of the latter in treating bulimic patients is discussed. A practical approach to the management of these patients is outlined. PMID- 2580332 TI - Complicated pancreatic inflammatory disease: diagnostic and therapeutic role of interventional radiology. AB - Diagnostic and therapeutic interventional radiology techniques in 41 patients with complications of pancreatic inflammatory disease (noninfected pseudocyst, infected pseudocyst, phlegmon, abscess, hemorrhagic pancreatitis) are described. Computed tomography or ultrasound-guided aspiration or percutaneous pancreatic ductography enabled specific diagnoses in 43 of 45 patients (96%). In almost half the patients, diagnostic aspiration with 22-gauge needles was unsuccessful due to viscous contents or firm cavity walls. Single-step needle aspiration of noninfected pseudocysts was successful in only three of ten patients (30%). Catheter drainage cured six of seven noninfected pseudocysts (85.7%) and seven of nine infected pseudocysts (77.7%). Pancreatic phlegmons were aspirated in five patients to exclude secondary infection and help determine the need for surgery. Pancreatic abscesses were drained successfully in nine of 13 patients (69.2%); temporizing benefit was achieved in the other four who eventually underwent surgery in improved condition. Early diagnosis of the complications of pancreatitis may be established almost uniformly, and at least 70% of patients with infected or noninfected pseudocysts and pancreatic abscesses may be cured by nonoperative drainage. PMID- 2580334 TI - [Transrectal prostatic sonography. Evaluation of a pilot study]. AB - The method of transrectal prostatic sonography is described. Evaluation of over 2700 examinations indicates a sensitivity and specificity for prostatic carcinomas of 88.7% and 97.3% respectively. The value of this new imaging method for the early recognition of an early carcinoma, for its staging and for controlling treatment has been investigated. Sonographic determination of the size of the prostate and a comparison of the transrectal and suprapubic approach are discussed. PMID- 2580333 TI - Biodistribution of radiolabeled lymphocytes. AB - Factors that might affect the biodistribution and clinical utility of radiolabeled lymphocytes were evaluated in experimental animals. Indium-111 (In 111) labeled lymphocytes (10(7)-10(9) syngeneic or allogeneic cells; 1-10 microCi [.037-.37 MBq]/10(8) cells) obtained from peripheral blood, lymph node, or spleen were found in significant amounts in the lymphoid tissues of Lewis rats as early as 3 hours after infusion. A progressive increase in nodal activity with concomitant fall of activity in other organs followed, indicating active recirculation of the lymphocytes. However, In-111 labeled thymocytes or xenogeneic lymphocytes failed to accumulate in lymphoid tissue. In vitro irradiation of the In-111 labeled lymphocytes (100-400 rads [1-4 Gy]) before in vivo administration and increase of the In-111 to 40 microCi [1.48 MBq]/10(8) lymphocytes resulted in no detectable lymphocyte recirculation and/or reduced localization in lymphoid tissue. Splenectomized animals and those sensitized to an organ allograft before cell infusion showed increased activity in their bone marrow. These results suggest that the source of the injected cells, cell irradiation dose level, and host sensitization should be considered when radiolabeled lymphocytes are being prepared for use in clinical diagnosis and therapy. PMID- 2580335 TI - Sexual changes in patients and partners following stroke. PMID- 2580337 TI - [Late asthmatic response]. PMID- 2580336 TI - The Na+/Ca2+ exchange system of the liver cell. AB - The efflux of 45Ca (Caeff) from rat liver slices incubated in a Krebs Ringer bicarbonate buffer showed two components with first order rate constants (kCa) of 0.0625 min-1 and 0.0101 min-1 respectively. The slow component corresponds to Caeff from the intracellular medium. Ouabain decreased kCa from the slow component (ksCa) by about 30%. External Na+ or Ca2+ did not affect ksCa. However, the inhibitory effect of ouabain was not observed in the absence of either Na+ or Ca2+ from the incubation medium. Concomitant to a decrease in ksCa, ouabain increased 45Ca uptake (Caup) by about 30%. Sodium ionophores also increased Caup, an effect which was not observed in the absence of external Na+. 22Na efflux was inhibited 50% by ouabain. In the presence of ouabain, external Ca2+ was able to significantly increase ksNa from 0.0475 min-1 to 0.0506 min-1. External Na+ dit not affect ksCa from preloaded slices containing high calcium and low sodium when incubated in a Ca2+-free medium. These results would indicate that a Na+/Ca2+ exchange system in operative in the plasma membrane of the hepatocyte. It is estimated that about 60% of the calcium entering the hepatocyte moves in through this exchanger. The evidence obtained also suggests that the Na+/Ca2+ exchanger operates unidirectionally, extruding internal Na+ in exchange for external Ca2+. PMID- 2580339 TI - [Anesthesia and recovery in cases of mandibular trauma]. PMID- 2580338 TI - Some properties of calcium-induced contraction in the isolated human and guinea pig tracheal smooth muscle. AB - We studied the effects of the cyclooxygenase inhibitors, indomethacin and aspirin, the leukotriene antagonist, FPL 55712 and the Ca antagonist, verapamil on basal tone and Ca-induced contractions in the human and guinea-pig tracheal muscle. Indomethacin and aspirin usually increased spontaneous tone or Ca-induced contractions in human strips, while consistently decreased tension development in the guinea-pig muscle. FPL 55712 strongly reduced contractions in the human, whereas it had a very weak effect on the guinea-pig muscle. Verapamil had a small inhibitory effect in the human trachea, either at 5.9 or 40 mM K, but markedly suppressed Ca-induced contractions of guinea-pig trachea in 40 mM K and had little effect on contractions in 5.9 mM K in this tissue. It is concluded that active tone in the two different tracheal muscles were controlled by different processes; that different arachidonate by-products may exert an effect on basal tone in the two different muscles; and that different plasma membrane Ca channels may be operative under basal conditions in the different muscles. PMID- 2580340 TI - [The shoulder in hemiplegic patients]. PMID- 2580341 TI - [Early psychomotor development--normal and abnormal. References for the detection and evaluation of development disorders]. PMID- 2580342 TI - [Is serum alphafetoprotein a marker for the prenatal diagnosis of trisomy?]. PMID- 2580343 TI - Experimental visna in Icelandic sheep: the prototype lentiviral infection. AB - A brief review of experimental infection of Icelandic sheep following intracerebral inoculation of neurotropic strains of visna virus is presented. In vivo replication of the virus is restricted, so that some cells carry the deoxyribonucleic acid provirus as an unexpressed genome. This cellular restriction plays a major role in the slow progression of the infection, abetted by neutralizing antibody in serum and spinal fluid. The latent provirus maintains the viral genome in the presence of an active immune response, since immune surveillance cannot recognize cells that are not synthesizing viral antigens. Infected Icelandic sheep experience two types of diseases of the central nervous system: a subclinical subacute encephalitis begins within weeks of infection in most sheep; and at irregular intervals from 0.5-8 years after infection, clinical paresis develops in the majority of Icelandic sheep and is accompanied by discrete focal demyelinating lesions in the spinal cord. The subacute encephalomyelitis is probably mediated by an antiviral cellular immune response, whereas the pathogenesis of the focal demyelinating lesions is still obscure. During persistent infection there is some selection for neutralization-resistant antigenic variants of the infecting serotype, and these are isolated at a frequency of approximately 15%. However, variants do not replace the infecting serotype, and antigenic drift does not appear essential for persistence of visna virus or for the occurrence of demyelinating lesions. PMID- 2580344 TI - [Preoperative nursing care for renal lithiasis]. PMID- 2580345 TI - Organ transplants. A complex gift of life. PMID- 2580346 TI - The Israeli high-risk study: statistical overview and discussion. AB - We have attempted to provide an overview of the initial evaluation of high-risk and control children. Summary measures of pathology were calculated for each clinical evaluation and objective test of the subjects. Correlational analysis revealed a pattern of intercorrelations among clinical subjective measures of pathology, and among objective measures, with no significant cross-correlations between the two types of measures. The one exception was the presence of neurological soft signs, which tended to correlate with both clinically and objectively measured pathology. Cluster analysis revealed three groups of subjects: a small group of index subjects who performed poorly on both clinical and objective measures; a larger cluster, predominantly index subjects, who showed clinical but not objective pathology; and a third group, including most of the controls, who functioned relatively well on both types of measures. Index subjects tended to show more consistent pathology across both clinical-subjective and objective examinations than controls. We hypothesize that our results stem from underlying deficits in attention, motor function, and perceptual-motor integration in offspring of schizophrenic patients. The finding of an inverse relationship between degree of pathology and age among the index children raises the possibility that developmental lags also play a part in the pathology of our high-risk subjects. PMID- 2580347 TI - [Malignant-appearing retroperitoneal lymphography findings in Whipple's disease- a source of possible misdiagnosis]. AB - Whipple's disease may mimic clinically primary intestinal lymphoma. In addition, lymphographic findings in the paraaortic lymph nodes in Whipple's disease simulate malignant lymphoma. These severe tumor-like lymphographic changes are described in three cases of Whipple's disease. The data highlight the risk of misinterpreting of Whipple's disease as malignant lymphoma on the basis of clinical data and lymphographic findings. PMID- 2580348 TI - The product of the c-fms proto-oncogene: a glycoprotein with associated tyrosine kinase activity. AB - The c-fms proto-oncogene is a member of a gene family that has been implicated in tumorigenesis. Glycoproteins encoded by c-fms were identified in cat spleen cells by means of an immune-complex kinase assay performed with monoclonal antibodies to v-fms-coded epitopes. The major form of the normal cellular glycoprotein has an apparent molecular weight of 170,000 and, like the product of the viral oncogene, serves as a substrate for an associated tyrosine-specific protein kinase activity in vitro. The results suggest that the transforming glycoprotein specified by v-fms is a truncated form of a c-fms-coded growth factor receptor. PMID- 2580349 TI - Homology of beta-lactoglobulin, serum retinol-binding protein, and protein HC. AB - The milk protein beta-lactoglobulin has been extensively studied but its function has not been identified. A clue regarding the function of a protein can be obtained by discovering a genetic relationship with a protein of known function through comparisons of amino acid sequence. Such comparisons revealed that beta lactoglobulin is similar to human serum retinol-binding protein and to another human protein of unknown function known as complex-forming glycoprotein heterogeneous in charge (protein HC). beta-Lactoglobulins from several species have been found to bind retinol, while the absorption and fluorescence properties reported for the unidentified heterogeneous prosthetic group of protein HC are retinoid-like. The role of serum retinol-binding protein in vitamin A transport in the circulation suggests that the other two homologous proteins may function in the binding and transport of retinoids; beta-lactoglobulin may facilitate the absorption of vitamin A from milk and protein HC may mediate the excretion of retinol-derived metabolites. PMID- 2580350 TI - Selective extraction of small and large molecules from the cerebrospinal fluid by Purkinje neurons. AB - Cerebellar Purkinje neurons accumulated propidium iodide, granular blue, and horseradish peroxidase conjugated to wheat germ agglutinin but not unconjugated horseradish peroxidase, bisbenzimide, or Evans blue when these compounds were infused into the lateral cerebral ventricles of awake, unrestrained rats. Accumulation of propidium iodide by Purkinje neurons of the vermis was associated with a reproducible behavioral abnormality characterized by truncal tremor, ataxia, and nystagmus. Both the accumulation of propidium iodide in Purkinje cells and the behavioral abnormality were prevented by prior intracerebroventricular administration of ouabain or colchicine, drugs that block neuronal transport processes. The ability of cerebellar Purkinje neurons to extract small and large molecules from the cerebrospinal fluid has important implications for their physiology and pathology. PMID- 2580351 TI - Monoclonal antibody-directed radioimmunoassay detects cytochrome P-450 in human placenta and lymphocytes. AB - A multiplicity of cytochromes P-450 is responsible for the detoxification and activation of xenobiotics such as drugs and carcinogens. Individual differences in sensitivity to these agents may reside in the cytochrome P-450 phenotype. A monoclonal antibody-directed radioimmunoassay was developed that detects epitope specific cytochromes P-450 in human placentas and peripheral lymphocytes. Placentas from women who smoked cigarettes contained greater amounts of cytochrome P-450 with the monoclonal antibody-specific epitope than placentas from nonsmokers. The amount of this cytochrome P-450 in human peripheral lymphocytes increased after treatment of the mitogenized lymphocytes with the cytochrome P-450 inducer benz[a]anthracene. PMID- 2580352 TI - Brain dopamine and serotonin receptor sites revealed by digital subtraction autoradiography. AB - Autoradiography combined with image analysis permitted quantitative visualization of dopamine (D2) and serotonin (S2) binding sites in rat brain. Forebrain sections were incubated with tritiated spiroperidol alone or with tritiated spiroperidol plus unlabeled compounds that saturated the D2 or S2 sites. By subtracting the digitized image of an autoradiograph derived from the latter sections from that of the former, the D2 or S2 sites were specifically revealed. The resulting quantitative images demonstrate the differing anatomical distributions of these sites. The D2 site is largely restricted to the striatal complex (caudate-putamen, nucleus accumbens septi, and olfactory tubercle), whereas the S2 site is enriched in layer 5 of motor cortex, the perirhinal and cingulate cortices, and the claustrum. PMID- 2580353 TI - Diagnosis and treatment of neoplasms with radionuclide-labeled antibodies. AB - The in vivo use of radionuclide-labeled antibodies to several types of tumor associated antigens or products has proven to be a reliable method for defining primary, recurrent, metastatic, and occult carcinoma. Specificity for the radioimmunodetection procedure is high; however, the sensitivity varies depending on the size and site of the lesions. The relative roles of polyclonal- and monoclonal-type antibodies are still to be defined, since at this stage of development little difference can be demonstrated in the detection of tumor with either one. The introduction of emission computed tomography should simplify the imaging techniques appreciably and improve the resolution between nontarget and target radioactivity. Satisfactory radionuclide labels with photon energies more compatible with current imaging equipment will enhance resolution and sensitivity. PMID- 2580354 TI - Hormonal regulation of Na+ channels in tight epithelia. PMID- 2580355 TI - Rapid insertion and retrieval of pumps and channels into membranes by exocytosis and endocytosis. PMID- 2580356 TI - The developmental regulation of TTX-sensitive sodium channels in rat skeletal muscle in vivo and in vitro. PMID- 2580357 TI - Reconstructive spinal surgery as palliation for metastatic malignancies of the spine. AB - Metastatic tumors of the spine often cause severe pain and paralysis because of deformity and neural encroachment. As oncology now extends the life expectancies of these patients, spinal decompression and stabilization is necessary. We consider that prophylactic stabilization of the spine is analogous to prophylactic nailing of a femur with a pathologic lesion. Both the femur and spine are weight-bearing structures. The advent of segmental instrumentation makes this a feasible accomplishment with minimal morbidity. Seventeen patients with metastatic disease of the spine at Rush-Presbyterian-St. Luke's Medical Center, Chicago, were reviewed. All maintained spinal stability postoperatively. Eleven of the 17 had significant pain relief for 3 months or more. Five of 11 paralyzed patients had significant neural recovery. A classification for treatment purposes regardless of tissue type was developed. Once classified, the surgical goals for these patients were to decrease pain, to preserve or to improve neurologic function and to mobilize the patient without external orthosis. PMID- 2580358 TI - Evidence of hypoxaemia and distribution of minor haemoglobin components in the cord blood of neonates born to diabetic mothers. AB - The oxygenation status of normal and diabetic (White's classification A and B) mothers and their neonates was investigated. The diabetic patients had significantly increased maternal total haemoglobin and P50 values and the percentage of fetal haemoglobin was increased in cord blood taken at delivery in this group. There was a significant positive correlation between maternal P50 values and the percentage of fetal haemoglobin in cord blood. The cord blood 2,3 diphosphoglycerate, inorganic phosphate and P50 values were also increased in neonates born to diabetic mothers and these infants had a significantly increased birth weight ratio. The results are consistent with the presence of fetal hypoxaemia in the late third trimester of diabetic pregnancy in which obvious maternal vascular disease has been excluded. PMID- 2580359 TI - Abnormal serum protein levels in infants with hyaline membrane disease--evidence of an underlying immunological disorder. AB - Evidence is presented that newborn infants who develop hyaline membrane disease (HMD) have higher levels of serum alpha-fetoprotein (AFP) than comparable infants who do not show evidence of the disease. A hypothesis is put forward that HMD is the result of an immune reaction between mother and infant, which may commence as early as the 2nd trimester of pregnancy. It is postulated that HMD infants, who generally have raised levels of serum IgM, produce IgM antibodies to foreign maternal IgG and that this reaction between the infant's IgM and maternal IgG accounts for the signs of systemic disease at birth. The onset of breathing during the intrapartum period may lead to an exacerbation of the immune response in the lung. It is known that AFP suppresses T-cell-dependent antibody responses. The presence of raised AFP levels may be an attempt to prevent formation of fetal or infant IgG antibodies resulting in an uncontrolled immune response and a lethal outcome. PMID- 2580360 TI - Long term results of pancreaticojejunostomy in chronic pancreatitis. AB - Fifty-one consecutive pancreaticojejunostomies for pain in chronic pancreatitis performed during the years 1964 to 1983 have been reviewed. Mean observation time was 8.2 years. Information on alcohol consumption, pain intensity and clinical signs of pancreatic dysfunction was recorded at regular intervals. Operative mortality was nil. Analysis showed no difference between alcohol abusers and other patients with regard to calcification, ductal dilation or exocrine and endocrine insufficiency. Good to excellent pain relief was achieved in 65 per cent of abusers and 88 per cent of nonabusers and was stable for at least five years. Patients who are heavy and unremitting abusers did not get much pain relief as a result of the operation. Patency of the anastomosis does not seem to be crucial for pain relief after pancreaticojejunostomy. PMID- 2580361 TI - The effect of hemodilution upon patients with intermittent claudication. AB - Seventeen patients with stable intermittent claudication and a PCV of more than 0.45 were venesected until a PCV of 0.35 was achieved. Only patients that were not considered candidates for surgical treatment were entered into the study. Each patient acted as their own control and was studied twice before the venesection at a mean PCV of 0.49 then after achieving a PCV of 0.35 or less (mean PCV of 0.33), and finally one month after the last venesection (mean PCV of 0.37). Angina developed in one patient after the third venesection and was withdrawn from the study. In the remaining sixteen patients, blood flow of the calf muscle during exercise increased significantly after venesection from 5.90 to 8.84 milliliters per 100 grams per minute (p = 0.02). This was measured by xenon 133 clearance and a cadmium telluride detector. There was also a substantial decrease (p less than 0.001) in whole blood viscosity at both low and high shear stresses, but there was no change in plasma viscosity or plasma fibrinogen. Treadmill claudication distance improved in only two patients. Ten patients were tired when the PCV decreased to 0.35 and subjective claudication distance deteriorated in four of these patients. Subsequent isovolemic venesection with dextran 70 volume replacement to a PCV of 0.35 did not improve the response in the six patients restudied. We conclude that venesection did not benefit these patients with intermittent claudication and there was an unacceptable incidence of side effects. Therefore, we suggest that reducing the PCV to 0.35 should be avoided in patients with intermittent claudication who have been refused surgical treatment. PMID- 2580362 TI - Elevated rate of DNA synthesis and its correlation to cAMP-phosphodiesterase activity during induction of polydactyly in mouse embryos heterozygous for Hemimelia-extra toe (Hmx). AB - The induction of polydactyly in mouse embryos heterozygous for Hemimelia-extra toe (Hmx) is associated with aberrant outgrowth of the developing autopod on day 12 of gestation. We have quantitated the rate of DNA synthesis and the activity of cAMP-phosphodiesterase (PDE) that is characteristic of the prospective polydactylous region. Mid-stage 18 hind-limb buds were labeled with [3H]dThd either in situ using whole embryo culture, or as isolated preaxial autopod fragments cultured on a membrane substratum. The mean specific activities of incorporation were compared for normal (+/+) and mutant (Hmx/+) genotypes. A significant (P less than or equal to 0.01) 19% increase, peculiar to the prospective polydactylous region, was measured after 4 hours in embryo culture. The same increment was detected after 4 hours in organ culture, but was amplified linearly to 55% when incubation was extended to 20 hours. During this period, continuous exposure to 1.0 mM IBMX (3-isobutyl-1-methyl xanthine), an inhibitor of cAMP-PDE activity, "slowed down" the rate of DNA synthesis to untreated +/+ proportions. When cAMP-PDE activity was assayed in uncultured autopods, a significant (P less than or equal to 0.01) 18% increase was detected within the prospective polydactylous region specifically on stage 18 of gestation. This is the developmental phase during which polydactylous outgrowth is induced in situ. Thus, uncontrolled cAMP-PDE activity may, in part, provoke the enhanced rate of cell proliferation. PMID- 2580364 TI - An immunohistochemical study of keratin, carcinoembryonic antigen, human chorionic gonadotropin and alpha-fetoprotein in lung cancer. AB - Immunohistochemical staining utilizing a peroxidase-antiperoxidase (PAP) technique for keratin, carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) was performed on paraffin sections from 72 cases of lung cancer obtained at autopsy. Positive reaction was shown in 44% of the cases for keratin, 77% for CEA, and 58% for HCG. AFP was positive in only one case of large cell carcinoma. Keratin was positive in 100% of squamous cell carcinoma, 53% of adenocarcinoma, 15% of small cell carcinoma and 45% of large cell carcinoma. CEA showed positive staining in 90% of squamous cell carcinoma, 88% of adenocarcinoma, 58% of small cell carcinoma and 69% of large cell carcinoma. CEA was the most useful tumor marker for detection of all types of lung cancer. HCG was positive in 30% of squamous cell carcinoma, 100% of adenocarcinoma, 23% of small cell carcinoma and 56% of large cell carcinoma. PMID- 2580363 TI - Effect of plasma exchange on acute pancreatitis. AB - Plasma exchange was performed in dogs with acute experimental pancreatitis to examine clearance of pancreatic enzymes. Plasma exchange of about 1.6 liters reduced levels of serum amylase, lipase, and phospholipase A2 in a graded fashion down to about 50%. Plasma exchange of 4 liters in a patient with severe pancreatitis produced similar clearance curves of amylase, lipase, trypsin and elastase levels. PMID- 2580366 TI - A silver impregnation technique for normal axons in the human central nervous system for celloidin and epon sections, with substitutes for soft tap water. AB - An improved silver technique has been developed for human CNS axons in sections from celloidin blocks that resist impregnation because of prolonged storage in alcohol. This method also gives consistently good impregnation of recently fixed material, and thus is suitable for routine use. Slightly modified, the method is also successful with osmicated Epon embedded sections. The quality of silver impregnation in methods using tap water in the reducing solutions varies in different laboratories. Having established that hard water is essential, substitutes for soft water were sought and found. PMID- 2580365 TI - alpha 1-Microglobulin determination in urine for the early detection of renal tubular dysfunctions caused by exposure to cadmium. AB - The determination of alpha 1-microglobulin (alpha 1-m) in urine was compared with that of beta 2-microglobulin (beta 2-m) for the detection of renal tubular dysfunctions caused by exposure to cadmium. alpha 1-m In urine is stable down to pH 4.5, whereas beta 2-m degrades below pH 5.5. The relationship between the urinary pH and alpha 1-m or beta 2-m in urine showed that alpha 1-m was independent of urinary pH, whereas beta 2-m-concentration decreased as urinary pH fell to a pH level below 6. Without a pH effect, alpha 1-m was highly correlated with beta 2-m in urine (N = 174, r = 0.96) from Cd-polluted subjects with renal dysfunctions. Due to the greater stability of alpha 1-m in urine, alpha 1-m seemed to be more advantageous than beta 2-m for the detection of renal tubular dysfunctions caused by Cd. PMID- 2580367 TI - A simplified technique for preparing sections of osmium stained myelin sheaths. PMID- 2580368 TI - A rapid technique for obtaining air dried mitotic chromosomes from mosquito egg rafts. PMID- 2580369 TI - A glycol methacrylate method for the routine histologic evaluation of rat inner ear. AB - A method has been developed for the histologic evaluation of rat inner ear using glycol methacrylate (GMA) and steel knife sectioning. The necropsy, fixation, and histologic techniques described are not so complex and difficult as to preclude their routine use. The method is particularly useful in studies in which the entire inner ear of a large number of animals must be evaluated histologically. PMID- 2580370 TI - A new fluorescent test for cell vitality using calcofluor white M2R. AB - The fluorescent fabric-brightener dye, Calcofluor white M2R (CFW), can be used to distinguish between living and dead cells from a variety of animal and plant sources. CFW does not stain living mouse fibroblasts or trout red blood cells and stains only the cell walls in living cells from the epidermis of onion bulb scale, staminal hairs of Tradescantia, and longitudinal sections of broad bean stems and roots. Heat-killed plant or animal cells are recognized by their lightly stained cytoplasm and brightly stained nuclei. The optimum staining concentrations were very low (0.01% to 0.03%) and nontoxic. Using onion scale epidermis in which some cells had been killed by heating as a test system, and the plasmolysis-deplasmolysis rection as the ultimate test for cell vitality, results from CFW staining correctly predicted cell vitality for about 98% of the cells tested. This success rate was comparable to those for Evans blue, uranin or neutral red in this test system. PMID- 2580371 TI - Intensifier for Bodian staining of tissue sections and cell cultures. AB - Intensification of the standard Bodian silver stain with a poststaining photographic enhancer produces high resolution of fine cell processes such as axonal growth cones. This technique can be used on tissue sections and is especially useful for visualizing individual cells fixed in tissue cultures. PMID- 2580373 TI - Staining of different endocrine cells with hydrochloric acid-toluidine blue in Epon embedded rat tissue. AB - The usual HCl-toluidine blue staining of different endocrine cells is applicable to paraffin embedded material. A modification for Epon embedded tissue suitable for consecutive light and electron microscopic studies is described which makes it possible to find the same stained cell, both in a semithin section and in subsequent ultrathin sections. This method facilitates the search for scattered specific endocrine cells. Without removing the resin, sections of Epon embedded tissues were hydrolyzed for 17 hr in 1% HCl at 65 C and stained for 2 hr in 0.1% toluidine blue in McIlvaine buffer, pH 5.8. The following cells were stained: C cells in thyroid glands; A and D cells in pancreatic islets; B cells in anterior pituitary; G, D and Ec cells in the gastrointestinal tract; Ad cells of the adrenal medulla. PMID- 2580372 TI - New method for visualization of vascular networks in nonperfused fixed tissues. AB - A new method of visualizing the angioarchitecture of tissues has been developed that uses blood components in nonperfused materials. Tissue blocks are fixed in 4% paraformaldehyde and cut with a vibratome into 50-60 micron sections. Endogenous peroxidase in red blood cells is then reduced in the presence of hydrogen peroxide with the resultant oxidation of the chromogen 3,3' diaminobenzidine (DAB). This generates a dark, highly insoluble reaction product throughout the vascular system. The visualization of vascular components can be further enhanced by exposing the sections to peroxidase-conjugated IgG to increase the background staining of the blood plasma. The technique minimizes preparation artifact and permits the application of morphometric analytical methods, thus allowing parameters such as the volume density of the vascular bed to be quantified. PMID- 2580375 TI - [Characteristics of isolated cells stained with acridine orange with regard to their organ of origin]. PMID- 2580374 TI - Fluorescence microscopy with antisera against specific cellular structure: double photography method for cell identification in populations of multiple cell types. AB - Immunofluorescent staining techniques using antitubulin antibody have been difficult to apply to meiotic tissue (testis) because of the large number of cell types present. Such techniques customarily use a fluorescent dye to counterstain nuclei, and this counterstain is hard to distinguish because of the fluorescence of the antitubulin. By counterstaining with dilute hematoxylin, we can photograph the same field using UV and then conventional illumination. This double photography allows us to identify precisely the many types of cells present, and it will be a useful tool for reexamining the staging of spermatogenesis. PMID- 2580376 TI - [Stability of species-specific antigenic properties of serum proteins in blood stains]. PMID- 2580377 TI - [Treatment of hematoxylin- and eosin-stained histological specimens with other dyes]. PMID- 2580378 TI - An erythrocyte Pr auto-antibody with sialoglycoprotein specificity in a patient with purine nucleoside phosphorylase deficiency. AB - A warm auto-antibody with specificity in the Pr blood group system was demonstrated in the serum and red cell eluate of a patient with purine nucleoside phosphorylase (NP) deficiency. The antibody reacted with all cells tested except En(a-) red cells which lack glycophorin A, the major erythrocyte sialoglycoprotein. However, anti-Ena was ruled out by absorption of the antibody with En(a-) red cells. The antibody demonstrated similar serologic characteristics to Pra antibodies, except that those previously described were inactive with protease-treated red cells, while in this case, reactivity was destroyed by papain and ficin but maintained in the presence of trypsin. Inhibition analysis with purified glycoprotein fragments localized the predominant reactive antigen on the MN sialoglycoprotein between amino acid residues 40 and 61. Serologic tests demonstrated its presence in decreased amount on at least one other erythrocyte membrane structure. The serum from another patient with NP deficiency contained an autoantibody similar to the one described here. It may be of interest to explore the association of auto-antibodies to erythrocyte sialoglycoprotein antigens in NP and other immune deficiency states. PMID- 2580379 TI - [Transmembrane effects in the sodium pump system. II. The ratio of the sodium efflux to the sodium concentration in frog muscle in media with various sodium substitutes]. AB - The dependence of sodium efflux on the internal sodium concentration on sodium free magnesium, Tris, coline and lithium media was investigated on frog striated muscle. In all the sodium-substituted media, the efflux concentration curve was found to be dependent on the external rubidium concentration, being S-shaped at the saturating external rubidium (potassium) concentration and becoming close to linear at the low external rubidium concentration (0.5-1.0 microM). The maximal sodium efflux at saturating levels of internal sodium concentrations remains unchanged with various sodium substitutes in the medium, whereas the affinity constant of internal sodium sites is dependent on the external cations. PMID- 2580380 TI - Palliative cryosurgery for oral cavity malignant melanoma: a case report. AB - A case of unresectable malignant melanoma of the oral cavity, treated with cryosurgery, is reported. A complete remission of 10 months was obtained, followed by 2 local recurrences, both treated successfully (CR: 9 and 4 months). At 23 months after the first treatment, a new local recurrence was considered untreatable. PMID- 2580381 TI - [Morphine depot tablets compared with conventional morphine tablets in the treatment of cancer pain]. PMID- 2580382 TI - [Morphine prescriptions in hospital departments]. PMID- 2580383 TI - [Results of a double-blind study on the effectiveness of ERU (extractum radicis Urticae) capsules in conservative treatment of benign prostatic hyperplasia]. AB - In 50 patients with prostatic hyperplasia the effect on symptomatology and objective findings of ERU-capsules versus placebo was investigated in a double blind study over a 9 week treatment period. Admitted to the study were patients in phases I and II who had been referred to the clinic in order to evaluate up the indication for operation. Concerning subjective complaints there was an improvement in dysuric symptoms in both patient groups. The evaluation of the objective parameters showed significant differencies. There was a statistically highly significant (p = 0.0005) decrease of the sex hormone binding globulin in the group of patients treated with ERU as well as a significant improvement of the micturition volume and maximum urinary flow. The improvement of the average flow in the ERU group was not significant. The increase of residual urine volume in both groups seems not to be significant according to the Covariance-analysis and is difficult to interpret. It is assumed, that, up to a certain grade, for a selected group of patients, mainly in the phase of beginning decompensation, length and dosage of therapy were possibly not sufficiently adjusted. PMID- 2580385 TI - Morphological variations in keratinising epithelia in the beagle. AB - Six keratinising epithelia in the beagle have been studied using conventional histology and fluorescence methods to identify the nature of the keratin present. Three patterns of differentiation were identified, those present in areas of hairy skin, the foot pad and the tongue and nasal tip. In the first group, the epidermis is generally thin and exhibits a low mitotic rate but the keratin formed is mature. In the foot pad and tongue, which are examples of pressure keratinisation, the epidermis is appreciably thicker because of the presence of a phospholipid-rich cornified layer. A third form of keratinisation is seen in the nasal tip and in regions of the tongue, characterised by parakeratotic changes, high phospholipid accumulation and other features reported previously in keratinising epithelia subject to prolonged hydration. PMID- 2580384 TI - Seminoma with elevated human chorionic gonadotropin. The case for retroperitoneal lymph node dissection. AB - An elevated serum level of human chorionic gonadotropin (HCG) in a patient whose primary tumor histologically appears to be a pure seminoma implies the presence of syncytiotrophoblastic giant cells either detectable by careful step sectioning of the primary tumor or present in metastatic disease. Inasmuch as the malignant potential and radioresponsiveness of syncytiotrophoblastic giant cells are unknown and the serum elevation of HCG may signal metastatic embryonal carcinoma, retroperitoneal lymph node dissection with adjuvant chemotherapy dependent on pathologic staging should be considered for patients with seminoma and postorchiectomy elevated HCG levels. An illustrative case is herein reported. PMID- 2580386 TI - Virological, clinical and serological responses of sheep infected with tissue culture adapted bluetongue virus serotypes 10, 11, 13 and 17. AB - Sheep were experimentally infected with cloned strains of tissue culture adapted bluetongue virus (BTV) serotypes 10, 11, 13 and 17. All the infected animals developed viremia by Day 2 or 3 post-inoculation (P.I.) and reached maximum viremia on Day 7 P.I. The viremia lasted for 2 to 3 weeks. Animals infected with the different serotypes showed mild clinical bluetongue (BT) responses, characterized by pyrexia and leukopenia, which coincided with the peak of viremia. Antibodies appeared by Day 10 P.I. and reached maximum by Day 28 P.I. There was a temporal relationship between the increase in neutralizing antibody titer, the drop in titer and clearance of virus from the peripheral circulation. Recovery from primary infection protected the animals against secondary challenge with homologous virus. PMID- 2580387 TI - Stromal cells in primary myelofibrosis: ultrastructural observations. AB - The bone marrows of five patients with primary myelofibrosis at different stages of the disease have been studied. In the myelofibrotic bone marrow, associated with "reticulum cells", two other cell types have been identified, namely fibroblast-like and myofibroblast-like reticulum cells, as well as a spectrum of transitional forms. Our findings suggest that reticulum cells may represent a reserve stromal cell pool (i.e. primitive reticulum cells) able to modulate themselves and to transform differently according to functional requirements. Some suggestions regarding the functional significance of fibroblast-like and myofibroblast-like reticulum cells in primary myelofibrosis are suggested. PMID- 2580388 TI - Mucopolysaccharidosis-like alterations in cardiac valves of rats treated with tilorone. AB - The purpose of this study was to examine whether the aortic and mitral valves of rats are involved in the mucopolysaccharidosis-like disorder induced by tilorone. Rats were treated with large doses of the drug for periods of 1-21 weeks. After chronic drug treatment the leaflets of both heart valves were thickened and opaque. In all treated animals the spongiosa layer of the stroma was crowded with vacuolated cells; the fibrosa layer was altered only after prolonged treatment. Ultrastructurally, the vacuolated cells of the spongiosa could be identified as histiocytes and fibroblasts, the former being the most susceptible cell type. The fibroblasts of the fibrosa represented the least sensitive cell type. The histochemical results showed that the clear cytoplasmic vacuoles in the spongiosa cells were due to lysosomal storage of polyanionic material with staining characteristics similar to cartilage matrix. After discontinuation of drug treatment the alterations persisted for several weeks. The present study shows that heart valves are involved in the mucopolysaccharidosis-like disorder induced by tilorone. The molecular pathomechanism of the disorder and the exact identification of the storage material must await further analysis. PMID- 2580389 TI - The paracortical area in reactive lymph nodes demonstrating sinushistiocytosis. An enzyme- and immunohistochemical study. AB - The enzyme and immunohistochemical features of lymphnodes showing sinus histiocytosis have been studied. Sinus histiocytes with phenotype OKM1+ OKT4+ Leu3a+ To5+ OKIal- showed strong acid phosphatase and non-specific esterase, weak endogenous peroxidase and no ATPase activities. In nine out of ten lymph nodes, paracortical collections of dendritic OKT6+ OKIal+ cells were observed. In two of the four cases studied these dendritic cells showed strong ATPase activity. We suggest that the dendritic OKT6+ OKIal+ ATPase+ interfollicular cells represent newly arrived veiled cells (VC) which have entered the lymph node by the afferent lymph, settled in the interfollicular area and are probably involved in the induction of a cellular immune response. OKT6+ OKIal+ ATPase+ VC may subsequently transform into mature, OKT6- OKIal+ ATPase+ interdigitating reticulum cells which are involved in the negative feedback of the cellular immune response. The association with sinus histiocytosis is probably related to the fact that an increase in mononuclear phagocytes in the afferent lymph is accompanied by a relative increase in VC. Our results demonstrate that in lymph nodes showing sinus histiocytosis, two cell types increase in number, i.e. an Ia- sinusoidal cell, engaged in phagocytosis of foreign material, and an Ia+ dendritic cell in the interfollicular area, probably involved in the induction of a cellular immune response. PMID- 2580392 TI - 'Partial inhibition' of anti-Rg and anti-Ch reagents. II. Demonstration of separable antibodies for different determinants. AB - Partial inhibition (p.i.) of anti-Rg (Rodgers) and anti-Ch (Chido) has been detected by antisera considered to be polyspecific. By using cells and C4 from individuals that are p.i. of Rg and Ch in absorption and elution experiments with selected antisera, it has been possible to separate several specificities. 2 Rg determinants, Rg1 and Rg2, and 3 Ch determinants, Ch1, Ch2, and Ch3, are defined by specific antisera. Partial inhibitors for Rg lack Rg2 and for Ch lack Ch2 or Ch3. The results are discussed in relation to other complexities of C4 polymorphism. PMID- 2580391 TI - [Determination of acute-inflammatory-phase proteins in the blood serum of volunteers consuming diets with various protein levels consisting of optimum protein constituents]. AB - The immunodiffusion technique was employed to study the blood serum content of acute inflammation phase reactants (transferrin, alpha 1-antitrypsin, ceruloplasmin, alpha 2-macroglobulin, fibrinogen, plasminogen, orosomucoid, haptoglobin, albumin and prealbumin) in 8 practically healthy men in the background of insufficient protein supply to the body. It was established that reduction of protein quota in the diet to 5.0-8.2 g/day (according to nitrogen) led to a decrease in the concentration of transferrin, ceruloplasmin, alpha 1 antitrypsin, albumin and prealbumin. It is concluded that reduction in the titers of the study proteins under protein deficiency may bring about the loss or weakening of the important components of the body defense, which are mediated by the above-mentioned protein structures. PMID- 2580394 TI - [Pancreatic function in hepatitis A]. PMID- 2580393 TI - Li cold agglutinin: a further antibody recognizing sialic acid-dependent antigens fully expressed on newborn erythrocytes. AB - The cold agglutinin anti-Li recognizes a sialic acid-dependent antigen fully expressed only on newborn red cells. Although it resembles anti-i in all aspects except for its nonreactivity with neuraminidase-treated red cells, it is entirely different from anti-i, since sialic acid is not involved in i antigenic determinants. PMID- 2580390 TI - [Biosynthesis of nucleic acids and proteins in different time periods of development in experimental myocarditis]. AB - Biosynthesis of DNA, RNA and protein was studied in rat myocardium within 1, 3, 5, 7, 14, 21 and 28 days after administration of adrenaline toxic doses (300 mg/100 g of body mass). Synthesis of DNA was activated within 1-7 days, of total proteins--within 1-14 days, of RNA--within 1-"1 days, of action and myosin in myocardium--within 3-21 days. All the patterns studied were normalized within the subsequent periods (21-28 days) although they exceeded the control values. These data and morphological assays suggest that restoration processes were activated due to regeneration of the impaired cardiomyocytes or to proliferation of fibroblasts. PMID- 2580395 TI - [Amylolytic and peptide hydrolase activities of duodenal mucosa in patients with chronic atrophic gastritis]. PMID- 2580397 TI - [Are there mucoviscidosis specific humoral factors? 1: Properties, prevalence, preparation, formation]. AB - In 1967 Spock et al. reported on the serum of cystic fibrosis (CF) homozygotes containing a factor altering the coordination of ciliary motion in rabbit tracheal explants. Just in 1967 Mangos et al. found sweat and saliva from CF homozygotes having an inhibitory effect on sodium reabsorption in the rat parotid gland. Since that time the existence of CF specific humoral factors was supposed. Hitherto mainly biological tests (especially tests of ciliary dyskinesia) were used to prove these factors. These tests caused different results which even were doubtful with regard to the existence of CF specific proteins. Recently it is possible to differentiate between proteins with effects of ciliary dyskinesia and a CF specific protein by means of high sensitive biochemical and immunological methods of protein distinction. In future one can expect elucidation of question related to the importance of CF protein in pathogenesis and diagnosis of cystic fibrosis. PMID- 2580396 TI - [Current biochemical hypotheses of endogenous depression]. AB - In this short introductory review the current important working hypotheses of depression, the noradrenaline and serotonin hypotheses, are described and critically evaluated. Anticholinergic properties, co-modulation of various transmitters by different neuropeptides, great variations in the influence on the "re-uptake" mechanism for noradrenaline and serotonin with no effect by novel antidepressants like iprindole, mianserin and clenbuterol and variability to either stimulate or block receptor systems (alpha 1-, alpha 2-, beta-, serotonin , dopamine-, adenylate cyclase dependent-, histaminergic receptors and possibly others) might further indicate a complex pathobiochemical background to depression. More recently, a unified hypothesis has been presented on the basis of subsensitivity of the noradrenaline-sensitive adenylate cyclase and/or down regulation of the number of beta-receptors by antidepressants of otherwise different pharmacological properties. Furthermore, another hypothesis, the "brain area specific imbalance of neurotransmitter systems" tries to combine current knowledge of the biochemistry of depressive disorders, the different pharmacological profiles of antidepressants and the divergence of symptomatology in depressed patients. Since antidepressant activity of drugs is dependent on the functional state of pre- and postsynaptic neurotransmission it seems essential to define the basal activity of such systems in vivo and to study the functional change after therapy. Furthermore, phenomena like adaptation and tolerance must be considered in future research in order to get more detailed information about pathobiochemical processes causing depression. PMID- 2580398 TI - [O antigen factors in Escherichia coli 01 strains of patients with urinary tract infections]. PMID- 2580399 TI - [Tumor associated markers as organ-specific antigens of the human seminal plasma. II. Immunohistological studies]. AB - The serologically detected and immunochemically characterized Ca 19-9 antigen of the human seminal plasma (as a glycoprotein) could now be also immunohistochemically localized in the prostate gland as well as in the seminal vesicles of the human genital tract. We conclude, therefore, that the main biosynthesis of this organ-typical glycoprotein takes place in both tissues. With respect to the quantitative expression of the antigen, there are differences not only in connection with the property of Lewis blood group but obviously also with regard to functional tissue alterations partly dependent on hormones. Possible associations with infertility, autoimmune diseases, or AIDS cannot be excluded in case of this alloantigen containing neuraminic acid. PMID- 2580400 TI - [Are inflammation parameters true signs of activity? A contribution to the problem of process activity and progression in chronic polyarthritis]. AB - Among all laboratory parameters used today in the assessment of activity and progression of rheumatoid arthritis erythrocyte sedimentation rate (ESR) can only be recommended reservedly. ESR is influenced by anemia, reduction of plasma fibrinogen, dysproteinemia and by the concentration of acute phase proteins. Quantification of acute phase proteins especially of the C-reactive protein (CRP) correlates best with activity and progression of early forms of rheumatoid arthritis as well as with malignant courses. During the administration of alkylating agents - rise of ESR in spite of clinical improvement and decrease of CRP - and during antimalarials - clinical improvement, decrease of CRP and constant, unchanged ESR - the quantification of CRP turns out to be superior to ESR. PMID- 2580401 TI - [Cryosurgery in inoperable rectal cancer]. AB - 26 patients suffering from nonresectable adeno-carcinoma of the rectum have been treated since Sept. 1980. The mean age was 72 years. The temperature of the probe tip was -160 degrees C. A closed system with liquid nitrogen was used. In 12 patients there was an indication of systemic inoperability, 13 had an irremovable tumour or metastases. 1 patient refused curative operation. Cryosurgery was aimed at reducing the mass of rectal tumours and preventing colostomy. Colostomy could also be avoided in 12 of 14 patients suffering from stenosing tumours. The advantages of cryotherapy are outpatient treatment, no anaesthesia and minimal complications. Generally, this method will yield good results in palliative treatment of inoperable rectal carcinomata. PMID- 2580402 TI - [Cryotherapy of rectal cancer. Immunologic results]. AB - On the basis of experimental studies carried out in animals several authors could demonstrate that cryotherapy is able to induce a raise of auto- and tumour antibodies. The specificity of these reactions has been proved. Comparative analysis could verify greater immune response after 'in situ-destruction' of tumours than after conventional surgical excision. In 13 patients cryosurgically treated for inoperable rectal carcinoma a raised concentration of IgG and IgA could be shown in several patients in the area surrounding the carcinomatous cells by means of a direct immune fluorescent technique in biopsies of the tumour. Immune globulines of the class IgA seemed to be important. Our results suggest a probable correlation of immune response and clinical course. The prognostic value of our method has to be examined in a larger group of patients and laboratory experiments. Cryotherapy can be regarded as one of several possible forms of treatment to brake the barrier of immunity in cancer patients. PMID- 2580403 TI - [15 years' experiences with cryosurgical treatment of rectal cancer]. AB - The field of cryosurgery in proctology can be seen in therapy of inoperable anal and rectal carcinomas. It is aimed at improving life quality. The role of microcirculation as a factor causing a contrary heating effect can be proved by intravital microscopy. Cryodestruction is limited by this factor. By means Of measurements of temperature we know the boundaries of complete tissue destruction which is reached in a distance of 4-8 mm. Our own number of cases consists of 122 patients with a mean age of 72 years. PMID- 2580404 TI - [Relation between the body weight of the pregnant patient and her serum alpha fetoprotein levels]. AB - In 1000 singleton pregnancies between 16 and 18 weeks maternal serum alpha fetoprotein (AFP) levels were related to maternal weight. The heavier women had lower mean levels apparently as a result of the diluting effect of larger blood volume. Lighter women had higher AFP levels, perhaps on account of the greater concentration of AFP in their relatively smaller volume of blood. A policy of evaluating the maternal serum AFP level according to maternal weight among women with borderline positive results could reduce both the number of patients having a diagnostic amniocentesis, and the rate of false negative cases. PMID- 2580405 TI - [Differential diagnostic procedure in sonographically detected fetal cystic hygroma]. AB - A series of 5 consecutive cases of fetal cystic hygroma diagnosed prenatally in the second trimester by sonography within a year in an ultrasound screening program is presented. 3 fetuses had a 45,X karyotype, one fetus had a 47,XY,+21 chromosome constitution and in one case no cytogenetic abnormality could be found. Because there was a cleft palate present in this latter female fetus, it is possible that this was a case of the recently described malformation syndrome. 3 of the pregnancies with fetal cystic hygroma ended in spontaneous abortion, in the other 2 cases the parents decided after careful genetic counseling to have an elective termination of pregnancy. Although Turner syndrome is the most frequent finding in cases of nuchal hygroma detected in utero by ultrasound, careful sonographic and cytogenetic studies as well as a detailed family history have to be obtained to delineate the cause of the malformation. On autopsy in all 3 cases with 45,X karyotype there were streak gonads, in 2 cases an additional hypoplasia of the aortic arch was found. Amniotic fluid alpha-fetoprotein and acetylcholinesterase determinations did not prove to add any significant information to the ultrasound evaluation of fetal cystic hygroma. PMID- 2580406 TI - [Development of a method of obtaining peroxidase conjugates with anti immunoglobulin for immunoenzyme analysis]. AB - The results of the successive stages of preparing peroxidase-labeled anti immunoglobulins are presented. The schedules for the immunization of animals have been worked out with a view to prepare antisera to human gamma globulin and, subsequently, to isolate antibodies from them by different methods. The preparations obtained with the use of immunosorbent have proved to possess the highest serological activity. As the result of these investigations, a new method of binding, a modification of the glutaraldehyde method, has been proposed. The conjugates obtained by the proposed method are characterized by high serological activity, stability and good reproducibility. PMID- 2580407 TI - [Development of a diagnostic test system for detecting soluble staphylococcal antigens by an immunoenzyme method]. AB - ELISA is used for detecting the soluble staphylococcal antigen in patients with purulent septic infections. The optimum conditions for the assay have been established: the dose of staphylococcal gamma globulin for plate sensitization should be 5.0-10.0 micrograms/ml, the pH of the buffer solution 9.6-10.0, the time and temperature of incubation 18-20 hours at 4 degrees C or 5 hours at 37 degrees C. The possibility of using plates manufactured in the USSR has been shown. The sensitivity of the above diagnostic test system is 0.005 microgram/ml. PMID- 2580408 TI - [The Denver shunt in malignant ascites]. AB - Malignant ascites is often refractory to therapy and rapidly deteriorating the nutritional and physical state of the cancer patient. Nevertheless, ascites does not always implicate preterminal state of the cancer process (e.g. ovarian carcinoma). A short review is made of the pathophysiology of ascites in cirrhosis and in malignancy, and different modes of treatment are discussed. The results of medical therapy of malignant ascites (salt and water restriction, diuretics, intraperitoneal cytostatics or radiocolloids) are not convincing. The immunotherapy with OK-432, as worked out by Katano (16-46) has to prove its value. The best and most hopeful results in cases of massive previously resistant ascites, are obtained with a peritoneojugular shunt, improving immediately the nutritional status and life condition, providing excellent palliation. The superiority of the Denver shunt versus the Le Veen shunt has been assessed recently, especially for malignant ascites. Some technical and perioperative details merit more attention, to limit the high risk ratio. Control of the intrathoracic position of the catheter tip, the maintenance of the bloodflow in the jugular vein, the intramuscular tunnelisation of the peritoneal catheter, the discard of 3 or 5 liters ascitic fluid and the substitution of part of it by physiological fluid, perioperative prophylactic antibiotics and heparinisation, flow-rate control in the postoperative period by changing patients position, respiratory exercises, daily flushing, all those measures limit the risk of fibrinolysis (DIC), shunt occlusion, fluid overload and infection. The fear of metastasis by shunt is unfounded, since the survival of the primary tumor is mostly too short (41). The postoperative follow up in an intensive care unit is necessary during 24-72 hours. PMID- 2580409 TI - Cytologic detection of Cryptococcus neoformans in cerebrospinal fluid. Rapid screening methods. AB - Yeasts of Cryptococcus neoformans in cerebrospinal fluid (CSF) were studied using polarized light and fluorescence microscopy. Ultraviolet-induced fluorescence of wet-fixed, Papanicolaou-stained smears and polarization of air-dried, Diff-Quik or Leishman-stained preparations are complementary methods that allow for rapid screening for and immediate identification of Cryptococcus in cytologic preparations of CSF. PMID- 2580410 TI - Diagnosis of unsuspected pulmonary cryptococcosis with sputum cytology. AB - This paper describes our experience in the sputum cytology diagnosis of pulmonary cryptococcosis, the clinical diagnosis of which is usually difficult. The cytologic findings are described briefly along with other pertinent supportive data, and the importance of sputum cytology in the diagnosis of this clinically occult mycotic disease is emphasized. The cytologic examination of deep cough samples of sputum in cases with an appropriate clinical setting and pulmonary infiltrates not only can be a rewarding procedure but also can result in the institution of an appropriate line of treatment for the possible prevention of widespread dissemination. PMID- 2580411 TI - Fine needle aspiration cytology of granulomatous cryptococcosis of the lung. AB - A cryptococcal infection was diagnosed in a patient with a history of immunoblastic non-Hodgkin's lymphoma by fine needle aspiration (FNA) cytology of a pulmonary nodule. This case illustrates that granulomatous inflammation can be appreciated by FNA cytology and, when seen, should result in a search for the specific organism. This case also reemphasizes the value of FNA cytology in the management and follow-up of patients with malignancy or those being treated with chemotherapy. PMID- 2580413 TI - Diagnosis of prostatic leiomyosarcoma with fine needle aspiration cytology. AB - A case of prostatic leiomyosarcoma initially diagnosed by fine needle aspiration cytology is reported. The cytologic findings on prepared smears are described. The value of a cell block preparation of the aspirate in establishing a definite diagnosis is discussed, and the differential diagnosis is briefly discussed. PMID- 2580412 TI - Fine needle aspiration cytology of pulmonary infarct. AB - The cytologic features of a pulmonary infarct diagnosed by fine needle aspiration (FNA) cytology are reported in a 54-year-old white man with a prior history of renal transplant surgery. Although the diagnosis of pulmonary embolus was unsuspected, FNA cytology suggested the correct diagnosis, which was confirmed by subsequent radiologic studies. This is believed to be the first reported case of pulmonary infarct diagnosed by FNA cytology. Cytologic features of the entity are discussed along with potential sources for a false-positive diagnosis of malignancy. PMID- 2580414 TI - Cytologic changes simulating malignancy in thyrotoxic goiters treated with carbimazole. AB - The cytologic patterns in toxic goiters treated with carbimazole were studied. Most cases exhibited changes, especially the unusually large nuclei, that could be mistaken for malignancy in panoptic-stained material. Study of the nucleolar morphology by means of the toluidine blue stain, however, showed a clear difference from malignant nucleolar types, with the nucleoli displaying types as in the cells of benign euthyroid colloid goiters. No increased transcription activity was seen in the nuclei. Nucleolar staining is thus recommended to avoid diagnostic errors in these and similar atypical cases. The apparent cytostatic effect of carbimazole on thyroid cells is in accord with other reports in the literature. PMID- 2580416 TI - Photic responses of the retina at different ages: a comparative study using histochemical and biochemical methods. AB - The alkaline phosphatase and DNA-RNA activities in the retinas of young and old albino mice were determined histochemically after photic exposure. Different patterns between the two age groups were obtained for the alkaline phosphatase reaction before and after photic exposure. In the young animals, more retinal layers showed increased activity after exposure whereas in the old animals, the converse was true. DNA-RNA reaction also revealed decreased DNA activities in the old animals 30 h after exposure. The results were also correlated with biochemical studies on 2-deoxyglucose, dopamine and leucine uptakes. PMID- 2580415 TI - Improved transmission electron microscopy technique for the study of cytologic material. AB - A modification of the technique of Coleman et al for the preparation of single cells in cytologic specimens for electron microscopy (EM) is described. By employing materials in the initial cytologic processing that are useful for EM, such as a paraformaldehyde-glutaraldehyde fixative, lactated Ringer's solution as a rinsing medium, glycerol as a mounting medium and cacodylate buffer for removal of coverslips, the use of alcohol fixatives and standard mounting media could be avoided. This preserved the cytoplasmic detail, which is usually degenerated in cells removed from cytologic specimens and processed for EM. PMID- 2580417 TI - Indole levels in human lumbar and ventricular cerebrospinal fluid and the effect of L-tryptophan administration. AB - Levels of tryptophan (TRP), 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5 HT), and 5-hydroxyindoleacetic acid (5-HIAA) in human lumbar and ventricular cerebrospinal fluid (CSF) were measured by reversed phase liquid chromatography (HPLC) with electrochemical detection. The levels of TRP ranged from 1593 to 4865 nmol/l in ventricular (VF) and from 1257 to 2557 nmol/l in lumbar CSF. The level of 5-HTP varied from 1.1 to 68.9 nmol/l in VF and from 5.3 to 10.8 nmol/l in lumbar CSF; no previous reports of 5-HTP levels in CSF exist. The serotonin level was 1.9-27.3 nmol/l in VF and 5.7-12.0 nmol/l in lumbar CSF. The levels of 5-HIAA were considerably higher in VF than in lumbar fluid with respective means of 498 +/- 52.4 nmol/l and 112 +/- 15.6 nmol/l (P less than 0.001). An oral dose of 2 g L-tryptophan significantly increased all indole levels except that of 5-HT, both in patients with progressive myoclonus epilepsy and in controls. PMID- 2580418 TI - beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in obstetrical cases. AB - The plasma levels of beta-Thromboglobulin (beta-TG) and Platelet Factor 4 (PF4) were measured in patients during the normal obstetrical period and in pre eclampsia. A significant increase was observed in the two proteins with respect to the non-pregnant control group but no difference was seen between pregnancy and puerperium in either the normal or pre-eclamptic cases. The one significant variation in the concentration of the two proteins was a sharp rise during parturition. There was no correlation between beta-TG, PF4 and either the platelet count or creatinine but urea and uric acid did show a slight correlation with the two platelet proteins. PMID- 2580420 TI - Methylprednisolone acts at the endothelial cell level reducing inflammatory responses. PMID- 2580419 TI - Polyagglutinability due to loss of O-antigenic determinants in Pseudomonas aeruginosa strains isolated from cystic fibrosis patients. AB - O-polyagglutinable P. aeruginosa are prevalent among chronically infected cystic fibrosis patients. In the present work, one O-group 3, one O-group 9 and one polyagglutinable 0-3/9 strain were analysed by use of both corresponding group specific antisera against the O-antigen and polyspecific antisera against all extractable antigens of the 3 strains. Quantitative immunoelectrophoresis and classical tube-agglutination methods were employed in the analysis. The results showed that the polyagglutinable strain contained 0.1% and the 0-9 strain 1%, respectively, of the O-antigen-containing LPS present in the 0-3 strain. It is discussed whether these differences represent a gradual antigenic adjustment to the defence mechanisms of the chronically infected patients. PMID- 2580421 TI - Homicide, suicide and CSF 5-HIAA. AB - Concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 4-hydroxy-3-methoxyphenyl glycol (HMPG) in lumbar spinal fluid were measured by mass fragmentography in 16 men convicted for criminal homicide, 22 men who had attempted suicide, and 39 healthy male control subjects. Those men who had killed a sexual partner, and those who had attempted suicide, had lower levels of the serotonin metabolite, 5-HIAA in spinal fluid than the controls. It is suggested that low levels of 5-HIAA in spinal fluid reflect a disorder of serotonin turnover, which makes the individual more prone to acts of violence in states of emotional turmoil. PMID- 2580422 TI - Alaproclate a novel antidepressant? A biochemical and clinical comparison with zimeldine. AB - Clinical and biochemical effects of two selective 5-HT uptake inhibitors, zimeldine and alaproclate, were studied in 24 hospitalized patients with endogenous depression. According to a randomized parallel group design 14 patients were treated with zimeldine and 10 with alaproclate. The dosage of both zimeldine and alaproclate was 200 mg daily. For the evaluation of the clinical effect, Montgomery & Asberg Depression Rating Scale (MADRS) was used. Seven of 14 patients treated with zimeldine and seven of 10 treated with alaproclate improved. 5-HT uptake inhibition in patients' platelets and concentration of amine metabolites (5-HIAA, HVA, HMPG) in CSF were studied before and during treatment. After 3 weeks of treatment with zimeldine 5-HIAA and HMPG in CSF decreased significantly while HVA in CSF increased significantly. Zimeldine produced a significant 5-HT uptake inhibition in platelets. During treatment with alaproclate no significant change in amine metabolites concentration in CSF was found and there were no mean changes on 5-HT uptake inhibition in platelets. PMID- 2580423 TI - Preoperative irradiation of primarily non-resectable adenocarcinoma of the rectum and rectosigmoid. AB - In a series of 328 patients with adenocarcinoma of the rectum and rectosigmoid, 39 had a tumour which was considered locally non-resectable (19 patients) or borderline resectable (20 patients). Twenty-eight of these patients received radiation therapy with a daily target dose of 2 Gy up to a total of 46 Gy. If the tumour was still considered non-resectable 3 weeks later, radiation therapy was usually continued up to a total dose of 64 Gy together with 5-fluorouracil. Fifteen patients with a non-resectable tumour received radiation therapy up to a total dose of either 46 Gy (7 patients) or 64 Gy (8 patients). Only two patients underwent resection. Of the 20 patients with a tumour that was considered borderline resectable, 13 received 46 Gy. Nine patients in this group were radically resected. Totally 11 tumours were resected, constituting 39 per cent of the patients who were treated up to 46 Gy or more. Truly locally inoperable tumours in this series were thus rarely converted to extirpative tumours by means of radiation therapy. Most patients with a tumour considered borderline resectable seemed to benefit from the treatment. In addition, the palliative effect of radiation therapy was excellent. PMID- 2580424 TI - Mycobacterium avium-intracellulare complex enteritis: pseudo-Whipple disease in AIDS. PMID- 2580425 TI - Sonography and CT in staging nonseminomatous testicular tumors. AB - The usefulness of sonography and computed tomography (CT) in the clinical staging of nonseminomatous testes tumors was examined by retrospectively reviewing the clinical staging of 57 patients. Twenty-five patients had sonographic examinations; two were considered inadequate and there were no false-positive results. Understaging occurred in 13% (3/23), while the negative predictive value for sonography was 73% (8/11). CT was performed on 29 patients; no patients were overstaged and only one examination was inadequate due to technical reasons. Understaging occurred in 18% (5/28), and CT had a negative predictive value of 67% (8/12). A subgroup of 18 patients having both sonography and CT was examined, and each staging procedure had a 22% false-negative and a 0 false-positive rate. Twenty-seven lymphangiograms, 28 excretory urograms, and 49 tumor marker determinations were also performed on this patient population, and their false negative rates were 35%, 78%, and 61%, respectively. False-positive rates of 30% for lymphangiograms, 6% for tumor markers, and 0 for excretory urograms were also obtained. On the basis of these results, sonography and CT are equivalent and superior examinations that have a high degree of accuracy (90%) in predicting bulky metastatic disease, either stage B3 or C disease. All patients would have received appropriate therapy if both examinations were carried out. However, this same goal could have been achieved with greater cost efficiency by initial sonographic screening, followed by CT in only those patients with negative or inadequate sonographic examinations. PMID- 2580426 TI - Skin-surface touch print for diagnosing fungal infections. AB - The skin-surface touch print is a practical, easily performed and noninvasive method for obtaining a sample of infected stratum corneum or hair. This technique is particularly useful in diagnosing superficial fungal infections. With simple staining, fungal hyphae and spores can be readily visualized microscopically. This technique has been found to be as effective as the potassium hydroxide test. PMID- 2580427 TI - To beat or not to beat: arguments for use of the term ventricular premature depolarization. PMID- 2580428 TI - I still prefer ventricular premature complex. PMID- 2580430 TI - Early identification of learning problems in neonatal intensive care graduates. AB - Most investigators have documented a notable frequency of educational problems in children who received treatment in the neonatal intensive care unit (NICU). Seventy-four children born between 1972 and 1976 and in NICUs were followed up prospectively. At ages 3 to 6 years, preschool development was within the normal range on the McCarthy scales. A school problem, defined as grade repetition and/or special help in school, occurred in 32 (48.8%). Those with school problems had significantly lower scores on the McCarthy scales at 4 to 6 years and on the Woodcock Johnson test than the group without school problems. Children with school problems were classified correctly 60.3% of the time by duration of neonatal hospitalization, and 72% to 80.9% of the time by preschool development. If replicable, the data indicate that potential school problems can be identified sufficiently early in NICU nursery graduates that intervention could be started before they enter school. PMID- 2580431 TI - Platelet activity in mitral valve prolapse: a study of platelet aggregation, malondialdehyde production, and plasma beta-thromboglobulin. AB - Platelet aggregation, malondialdehyde (MDA) production, and recovery after aspirin (ASA) administration and plasma levels of beta-thromboglobulin (BTG) were determined in 40 asymptomatic patients with mitral valve prolapse (MVP) and 17 normal subjects. Platelet aggregation was similar in patients and controls, although two patients presented spontaneous aggregation. Production of MDA and plasma levels of BTG were higher in MVP than in controls; however, recovery after ASA was similar in both groups. The results further indicate that platelet hyperactivity is present in a significant number of asymptomatic patients with MVP. PMID- 2580429 TI - Paget's cells. New evidence linking mammary and extramammary Paget cells to a common cell phenotype. AB - Three mouse monoclonal anti-human cytokeratin antibodies were made against human sole epidermis. One of these (KA4) was shown to react with a variety of human simple epithelium, including eccrine and apocrine sweat glands and the luminal cells of the breast ducts and lobules, but failed to decorate interfollicular stratified squamous epithelium. This antibody reacted by the immunoblot technic with cytokeratins of Mr values 54, 46, and 40 kdaltons. KA4 reacted strongly with clear cells found in 11% of breast epithelium in clinically uninvolved nipples and with all Paget's cells in four cases of mammary and five cases of extramammary Paget's disease. These findings suggest a common cellular phenotype for Paget's cells and relates them to a population of cells found in breast epithelium. PMID- 2580432 TI - beta-Thromboglobulin in patients with breast cancer. AB - beta-Thromboglobulin (beta TG) plasma levels were determined in 52 female breast cancer patients at different stages and in 39 healthy controls (22 women and 17 men) of similar age distribution. Beta TG levels were high (mean +/- SD:61.6 +/- 59.1 ng/ml) in patients before any treatment compared to controls (mean +/- SD:21.2 +/- 7.4 ng/ml) and the difference was statistically significant (p less than 0.001). No correlation with disease stage was observed. No other coagulation parameters were abnormal except fibrinogen, which increased. Fibrinogen degradation products (FDP) also increased but only in metastatic patients. Chemotherapy appeared to induce a considerable decrease in initial values at the end of the first cycle without modifying the platelet count. In addition, an attempt was made to correlate the beta TG plasma level investigated serially for several months with disease evolution. PMID- 2580433 TI - Low molecular weight iron in guinea pig reticulocytes. AB - The low molecular weight iron found in the guinea pig reticulocyte has been partially characterized. On thin layer chromatography it is distinguishable from the iron complexes of a variety of nucleotides, sugars, and amino acids. On paper chromatography it comigrates with a 250-nm absorbing, orcinol-positive material. The eluted count peak contains phosphorus. Approximately 1 microgram of iron is recovered from 1 ml of hemolyzed red cells. Preparation under nitrogen improves recovery of low molecular weight iron, suggesting that the iron is in the ferrous oxidation state. PMID- 2580435 TI - Evaluation of two methods of patient education. PMID- 2580434 TI - Transfer of human and murine globin-gene sequences into transgenic mice. AB - We have studied the transfer of human and murine globin gene sequences into fertilized mouse oocytes by microinjection. Germline transmission was demonstrated for the human delta- and beta-globin genes contained in the bacteriophage lambda H beta G1. Expression of these human globin-gene sequences was not detectable in either erythroid or nonerythroid tissues. A recombinant plasmid containing the murine beta maj promoter region coupled to the prokaryotic coding sequence for galactokinase was also successfully transferred to two mice, and stable germline transmission of integrated DNA was demonstrated for at least 3 generations. Despite the presence of a murine globin-promoter sequence, expression of the mouse beta maj galactokinase fusion gene was not observed in primary or secondary animals in erythroid or nonerythroid tissues. Analysis of primary and secondary animals from both series of injections revealed extensive de novo methylation in the integrated microinjected DNA. Administration of 5 azacytidine to mice containing the mouse beta maj-promoted galactokinase gene resulted in partial hypomethylation was associated with an apparent two- to threefold increase in galactokinase (gal K) gene expression. PMID- 2580436 TI - Myelopathy following intrathecal chemotherapy in a patient with extensive Burkitt's lymphoma and altered immune status. AB - A 30-year-old homosexual man presented with widespread Burkitt's lymphoma. On the basis of immunologic and viral studies, he was suspected of having the acquired immune deficiency syndrome. Following chemotherapy that included intrathecal cytosine arabinoside and methotrexate, brain stem edema, paraplegia, and an elevated cerebrospinal fluid level of myelin basic protein developed. Autopsy revealed vacuolar demyelination of spinal cord, brain stem, and cerebellum. The pathologic findings were similar to those reported to occur in myelopathy associated with intrathecal chemotherapy, but far more extensive. The contribution of the suspected acquired immune deficiency syndrome is unknown. PMID- 2580437 TI - Free tissue transfer. PMID- 2580438 TI - The influence of oral contraceptives on the postmolar human chorionic gonadotropin regression curve. AB - This article reports a retrospective analysis of 149 evaluable cases of molar pregnancy managed at Women's Hospital, Los Angeles County/University of Southern California Medical Center, from January 1977, through June, 1983. In the 84 cases prior to 1981, the patients received estrogen-progestogen oral contraceptives after evacuation while the 55 patients seen after that used nonhormonal contraceptives. The frequency of abnormal regression of the serum beta-subunit of human chorionic gonadotropin in the two groups was not significantly different (22.6% in the hormonal contraception group versus 34.5% in the nonhormonal contraception group). The groups were compared for known and potential risk factors and were nearly identical with respect to patient age, parity, maternal blood type, and race. There were also no significant differences with respect to uterine size, preevacuation beta-subunit of human chorionic gonadotropin serum titer greater than 100,000 mIU/ml, and frequency of theca-lutein cysts. Gestational age was significantly shorter and the frequency of cases with a preevacuation beta-subunit of human chorionic gonadotropin serum titer greater than 250,000 mIU/ml significantly higher in the nonhormonal contraception group, indicating that the nonhormonal contraception group had a higher risk for abnormal human chorionic gonadotropin regression than the hormonal contraception group. We conclude that this study provides no evidence that the use of estrogen progestogen oral contraceptives prior to human chorionic gonadotropin remission increases the risk for invasive mole or choriocarcinoma following molar pregnancy. PMID- 2580439 TI - alpha-Fetoprotein: relationship between maternal serum and amniotic fluid levels. AB - Levels of alpha-fetoprotein were determined in 297 paired samples of maternal serum and amniotic fluid from patients with normal pregnancies at 16 to 17 completed weeks of gestation. Gestational ages were determined by menstrual history and ultrasonography, and the assays for alpha-fetoprotein were performed by a single reference laboratory. The results of the study failed to demonstrate any statistical relationship between the concentrations of alpha-fetoprotein in these two fluid compartments (r = 0.006). This finding was confirmed when the results at 16 and 17 weeks were analyzed individually. These findings indicate that amniotic fluid levels of alpha-fetoprotein cannot be predicted by those levels determined in maternal serum, and that simple diffusion is an inadequate explanation for the transfer of alpha-fetoprotein from amniotic fluid to maternal serum. The lack of correlation also emphasizes that the sensitivity and specificity of maternal serum alpha-fetoprotein screening for neural tube defects must continue to be based upon the detection rates in large population studies and the determination of "normal" values by reference laboratories. PMID- 2580440 TI - Hemorrhagic detachment of the peripheral retinal pigment epithelium. AB - Peripheral hemorrhagic detachments of the retinal pigment epithelium after choroidal neovascularization in age-related macular degeneration in the fellow eye have been reported only rarely. We report a case of a 75-year-old male with such involvement who presented with the acute onset of a shower of floaters in the right eye 9 months after argon laser photocoagulation of juxtafoveal choroidal neovascularization in his left eye. The peripheral hemorrhagic detachment resolved within one month. PMID- 2580441 TI - pp60c-src is expressed in human fetal and adult brain. AB - Human cells contain a tyrosine-specific protein kinase, pp60c-src, that is highly homologous to the oncogene product, pp60v-src, from Rous sarcoma virus but is of unknown function. The expression of human pp60c-src was examined in tissues obtained from human adults and fetuses of 20-32 weeks' gestational age. pp60c-src was quantitated in tissue extracts by measurement of its protein kinase activity by the use of the immune complex protein kinase assay. Brain showed the highest levels of pp60c-src protein kinase activity, but all other human tissues examined had significant levels. Fetal tissues, including brain, showed three- to eight fold higher levels of pp60c-src kinase activity than the corresponding adult tissues. pp60c-src kinase was found to be uniformly distributed in the adult brain; frontal, occipital, and parietal cortex, and cerebellum expressed equivalent amounts of pp60c-src kinase activity. The protein kinase activity in human tissues exhibited properties characteristic of pp60c-src in other species, namely, tyrosine-specific phosphorylation of specific antibody heavy chains, autophosphorylation of a 60,000 Mr protein following immunoprecipitation with a monoclonal antibody specific for pp60src, and sensitivity to inhibition by P1,P4 di(adenosine-5')tetraphosphate. The high levels of human pp60c-src in fetal tissues, particularly in brain, suggest a possible function in developmental processes. PMID- 2580442 TI - Salivary gland components involved in the formation of squamous metaplasia. AB - Squamous metaplasia is not an uncommon feature of a number of salivary gland lesions. Arterial ligation of rat submandibular and sublingual salivary glands was used for study of the processes and cell types involved in the development of the squamous metaplasia that occurs in ischemic and infarcted portions of gland parenchyma 6 to 8 days following vessel ligation. Light and electron micrographs show that the principal portion of salivary gland tissue undergoing squamous metaplasia is the acinar-intercalated duct cell complex. Early stages of this process involve a gradual dedifferentiation of acinar cells and hyperplasia of acinar, duct luminal cells, and myoepithelium. Subsequently, both luminal and myoepithelial cells have increasing accumulation of tonofilaments and formation of desmosomes, and centrally located cells may undergo keratinization. Immunohistochemical staining of ischemic salivary gland tissue with developing squamous metaplasia was performed with the use of rabbit antisera to human epidermal and Mallory body cytokeratins. The two antisera gave complementary patterns in normal acini and ducts, with antibody to epidermal cytokeratin (ECK) staining only myoepithelial cells and antibody to Mallory body cytokeratin (MBCK) staining mainly luminal epithelial cells. In early phases of squamous metaplasia (6 days after ligation), antibody to ECK stained central and peripheral (myoepithelial) cells, but by 8 days after ligation only central cells were stained. At 6 days after ligation, a proportion of central cells in squamoid clusters stained with antibody to MBCK, and myoepithelial cells were unstained. By 8 days after arterial ligation, cell clusters exhibiting squamous metaplasia were completely unstained with antibody to MBCK, despite the presence ultrastructurally of numerous tonofilament bundles in both types of cells forming these clusters. The propensity for squamous alteration of acinar-intercalated duct complexes has important connotations for salivary gland tumors such as pleomorphic adenoma and mucoepidermoid carcinoma. PMID- 2580444 TI - Permeability of zymogen granule membrane to protein. AB - The evidence that the membrane of the pancreatic zymogen granule is permeable to its contained secretory proteins is outlined. Included is a discussion of the nature and characteristics of the equilibrium-dependent release of protein from isolated granules, the evidence for the permeability of the granule membrane to digestive enzyme protein in situ, and the seeming paradox that isolated granules release protein in medium similar to that thought to exist in the cell. The permeability hypothesis is reconsidered here in light of recent claims of stable nonpermeable granules. PMID- 2580445 TI - Mucin depletion in the intestine of malnourished rats. AB - The effects of malnutrition on mucosal goblet cell mucin levels were studied in rats deprived of 50% of their daily intake, as judged by pair-fed, age-matched control animals, for 5 wk. Average daily weight gain was 0.7 g/day compared with 5.8 g in age-matched (AM) rats; final weight was 246 +/- 9 g compared with 406 +/ 4 g. Immunoassayable mucin, sucrase, protein, and DNA were assayed in mucosal scrapings from the proximal, middle, and distal segments of the small intestine in malnourished rats, AM rats, and a third group of low-weight, less mature (LM) rats. Total protein, total DNA, and protein-to-DNA ratios in malnourished rats were unchanged compared with AM control rats and often higher than levels in LM control rats. In malnourished animals, mucin concentration per milligram protein was significantly decreased below AM control animals in the upper two segments and below LM control animals in all segments. Mucin concentration per milligram DNA was significantly lower in malnourished rats than in all segments of both control groups. In contrast, sucrase activity per milligram protein or DNA was either unchanged or increased in the malnourished rats, indicating that the reduction in mucin concentration was selective and did not reflect all surface glycoproteins. Isolated mucins from malnourished and AM control rats were chemically similar, and the affinity and number of antigenic determinants were the same. Malnutrition therefore leads to an absolute decrease in intestinal mucin rather than reduced molecular antigenicity. Impaired capacity to maintain mucosal mucin content may be a factor in reducing intestinal resistance to enteric infection in malnutrition. PMID- 2580443 TI - Cellular differentiation of epithelioid sarcoma. An electron-microscopic, enzyme histochemical, and immunohistochemical study. AB - For the purpose of clarifying cellular differentiation of epithelioid sarcoma, studies based on various methods were performed. Enzyme histochemical studies showed that epithelioid sarcoma tumor cells have characteristics intermediate between epithelial cells and the large plump cells of synovial sarcoma-incomplete epithelial differentiation. For alkaline phosphatase and adenosine triphosphatase particularly, positive cells and negative cells coexisted, as in the large plump cells of synovial sarcoma. Immunohistochemical studies for alpha 1-antitrypsin, alpha 1-antichymotrypsin, vimentin, and keratin also showed that epithelioid sarcoma tumor cells are very similar to the large plump cells of synovial sarcoma and have incomplete epithelial differentiation. For example, the examinations of serial sections and double staining methods revealed that keratin-positive cells are always vimentin-positive in epithelioid sarcoma and in the monophasic area of synovial sarcoma. Electron-microscopically, bundles of intermediate filaments and filopodia toward the intercellular lumen were observed, as in the monophasic area of synovial sarcoma. The results of enzyme-histochemical and immunohistochemical studies of non-neoplastic synovial lining cells, performed here for the first time, are also discussed. PMID- 2580447 TI - Effect of Ag+ on isolated bullfrog gastric mucosa. AB - In nitrate solutions, Ag+ added to the luminal side had marked effects on transmucosal conductance and potential difference (PD). Conductance increased quickly (85% within 60 s, 420% by 10 min); PD increased initially (11% within 30 s) and then fell precipitously (58% decreased within 2 min, 85% decreased by 10 min). During this period, no increase in mannitol permeability was found. These changes were essentially similar in histamine-stimulated, spontaneously secreting, and metiamide-inhibited fundic mucosae. Replacement of luminal Na+ by choline had no effect on the changes observed. Similar changes occurred also in the antrum. In SO2-4 media the increases in conductance occurred more slowly (40% within 2 min, 150% after 10 min); PD increased initially for 4-6 min and then slowly declined over 60 min to 74% of control values. After Ag+ treatment, replacement of luminal SO2-4 by nitrate led to an inversion of the PD by up to 20 mV (serosa -ve). Brief exposure of the mucosa (2 min) to Ag+ did not show any obvious damage, although surface cells were damaged following more prolonged exposures. After a 4-min treatment with Ag+, electrical and secretory parameters showed substantial recoveries. Ag+ appears to increase anion conductance; these effects appear to occur on the apical membranes of tubular and/or surface cells of the fundus and antrum. PMID- 2580446 TI - Differential effects of corticosteroids on Na+ transport in rat distal colon in vitro. AB - We studied rat distal colon during in vitro incubation with aldosterone and dexamethasone. Both hormones caused short-circuit current (Isc) to increase with a latency period of approximately 3 h. At the 7th h of incubation, control colons had a Isc of 72 +/- 8 microA . cm-2 while tissues incubated with 10(-5) M aldosterone and 10(-8) M dexamethasone, the respective maximal stimulatory concentrations, had similarly increased Isc, 211 +/- 21 and 185 +/- 18 microA . cm-2, respectively. The increase in Isc induced by steroids reflected increased net sodium transport: control, 3.4 +/- 0.8; aldosterone, 6.7 +/- 0.7 (P less than 0.05); and dexamethasone, 7.5 +/- 1.0 mueq . h-1 . cm-2 (P less than 0.025). Spironolactone inhibited the response to both steroids, but the molar ratio of antagonist to agonist was less for aldosterone (approximately 5,000:1) than for dexamethasone (approximately 50,000:1). Amiloride inhibited a greater fraction of aldosterone-induced Isc (0.70 +/- 0.07) than that of dexamethasone (0.37 +/- 0.07; P less than 0.025). The latter value was similar to the effect of amiloride on control tissues (0.35 +/- 0.04). These data provide evidence that the cellular mechanisms by which aldosterone and dexamethasone induce Na+ transport are different. PMID- 2580449 TI - Dextran and capillary filtration coefficient in cat hindlimb. AB - To investigate the possible mechanisms through which dextran modifies capillary filtration coefficient (CFC), the effects of perfusion with a protein-free dextran solution were compared with those of perfusion with a Ringerlike solution. With the use of the isolated cat hindlimb, CFC was measured during perfusion at constant flow with three solutions, a control blood-albumin mixture, a Ringerlike solution called dialysate, and 3.7 g/dl dextran dissolved in dialysate. The solutions were warmed to 37-38 degrees C, bubbled with 95% O2-5% CO2, and contained 0.015 g/dl or more papaverine. CFC was calculated from the rate of limb weight gain following a step increase in venous pressure. Dextran perfusion increased CFC to 2.0 +/- 0.2 (SD, n = 8) times control, which was significantly less (P less than 0.001) than 3.1 +/- 0.6 (n = 8) times control previously reported for dialysate perfusion. The difference between the measured viscosity of dextran (1.35 cP) and dialysate (0.72) could account for this reduction. However, when a dialysate perfusion followed a dextran perfusion, CFC only increased to 2.3 +/- 0.4 (n = 8) times control. This value is also significantly less (P less than 0.01) than 3.1. This observation suggests 1) that dextran is retained within the transcapillary channel and 2) that dextran reduces CFC mainly by partially blocking the transcapillary channel rather than by increasing viscosity. PMID- 2580448 TI - Carbobenzoxy amino acids: structural requirements for cholecystokinin receptor antagonist activity. AB - We used dispersed acini prepared from guinea pig pancreas to examine 28 carbobenzoxy (CBZ) amino acids for their abilities to function as cholecystokinin receptor antagonists. All amino acid derivatives tested, except for CBZ-alanine, CBZ-glycine, and N alpha-CBZ-lysine, were able to inhibit the stimulation of amylase secretion caused by the C-terminal octapeptide of cholecystokinin. In general, there was a good correlation between the ability of a carbobenzoxy amino acid to inhibit stimulated amylase secretion and the ability of the amino acid derivative to inhibit binding of 125I-cholecystokinin. The inhibition of cholecystokinin-stimulated amylase secretion was competitive, fully reversible, and specific for those secretagogues that interact with the cholecystokinin receptor. The potencies with which the various carbobenzoxy amino acids inhibited the action of cholecystokinin varied 100-fold and CBZ-cystine was the most potent cholecystokinin receptor antagonist. This variation in potency was primarily but not exclusively a function of the hydrophobicity of the amino acid side chain. PMID- 2580450 TI - Immunological specificity of hexosaminidases from human seminal plasma. AB - Two isozymes of hexosaminidases (Hex) were purified from human seminal plasma and found to be homogeneous as revealed by immunoelectrophoresis and immunodiffusion experiments. Anti-Hex A antibodies were precipitated with isozyme B and vice versa. Though the precipitin arcs were equally stained for protein in these two antigen and antibody systems, enzyme activity was weakly stained in the reverse systems (ie, Anti-Hex A with Hex B and Anti-Hex B with Hex A). Thus, some common sequential antigenic determinants were indicated in two isozymes of Hex. On the other hand, loss of enzyme activity in the precipitate of reverse antigen antibody complexes as compared to direct system (Anti-Hex A with Hex A and Anti Hex B with Hex B) revealed that the two isozymes are present in different sequential and conformational states near the active sites. Moreover, antibodies of both forms of Hex cross-reacted with human sperm and reproductive and other vital organs such as kidney, liver, lung, pancreas, and spleen. Though monkey tissues also cross-reacted with human seminal plasma Hex-antisera, mouse, rat, and goat testis and epididymis extracts failed to show any cross-reaction. It is concluded that human Hex(s) are tissue nonspecific but appear to be specific to the human and the subhuman primates. PMID- 2580451 TI - Comparison of four schistosome excretory-secretory antigens: phenol sulfuric test active peak, cathodic circulating antigen, gut-associated proteoglycan, and circulating anodic antigen. AB - Several carbohydrate-containing antigens of schistosomes have been characterized and tests for these antigens or for the corresponding antibodies are increasingly being used for the diagnosis and clinical analysis of human schistosomiasis. Phenol sulfuric active peak (PSAP) and cathodic circulating antigen (CCA) are 2 soluble glycoproteins found in adult worms of Schistosoma mansoni. These antigens have some similar characteristics including solubility in trichloroacetic acid and non-binding or weak binding to DEAE cellulose which suggests these 2 compounds to be identical. PSAP and CCA were therefore compared using radioimmunoassays employing monoclonal antibodies to CCA and radiolabeled PSAP as well as inhibitory assays using the original glycoproteins as inhibitors. By these criteria PSAP and CCA were found to be different glycoproteins. Using similar techniques, 2 anodic schistosome compounds, gut-associated proteoglycan (GASP) and circulating anodic antigen (CAA) were found to be identical. We now propose to call this later material GASCAP (gut-associated circulating anodic proteoglycan). PMID- 2580452 TI - Identification of pathogenic Leishmania promastigotes by DNA: DNA hybridization with kinetoplast DNA cloned into E. coli plasmids. AB - We report the characterization of Leishmania (L. infantum, L. donovani, and L. major) kinetoplast DNA (kDNA) by the use of restriction endonuclease digestion patterns and Southern hybridizations. Overall, the sizes and fragment patterns of MspI restriction endonuclease-produced DNA fragments vary from species to species. However, kDNA isolates from different species and strains cross-reacted to a great extent in Southern hybridization experiments. Only kDNA isolated from L. infantum and L. major had little homology during hybridization reactions. To prepare DNA probes that would differentiate between species of Leishmania, minicircle kDNA was digested with restriction enzymes and ligated to an E. coli plasmid. Several plasmids were isolated that specifically detect in hybridization experiments as few as 5 X 10(3) L. donovani or L. infantum promastigotes lysed on nitrocellulose filters. PMID- 2580454 TI - Conservation of pancreatic tissue by combined gastric, biliary, and pancreatic duct drainage for pain from chronic pancreatitis. AB - In patients with chronic pancreatitis, the sclerosing process of the pancreas may constrict not only the pancreatic duct for also the bile duct and duodenum. This study analyzes the prevalence of these obstructive lesions in 58 consecutive patients with chronic pancreatitis requiring surgery for either pain (57 patients) or for painless jaundice (1 patient). There was significant biliary obstruction in 21, 4 of whom also had symptomatic duodenal obstruction. All 21 patients with biliary and duodenal obstruction were among the 38 with a dilated pancreatic duct suitable for pancreaticojejunostomy (modified Puestow procedure). None of the 20 patients with small duct pancreatitis had biliary or duodenal obstruction. Pseudocysts were distributed evenly between the two groups (9 of 38 patients with a dilated duct versus 4 of 20 patients with small duct pancreatitis). Pancreaticojejunostomy combined with choledochoenterostomy and gastrojejunostomy in appropriately selected patients provided good to excellent long-term (mean 3.6 years) relief of pain in 30 of 36 patients (83 percent). There was no correlation between successful relief of pain and development of pancreatic exocrine or endocrine insufficiency or calcification. Stenosis of the bile duct developed some years subsequent to pancreaticojejunostomy in four patients and required a second operation for choledochoenterostomy in three. Three other patients required secondary pancreatic resections due to failure of the pancreaticojejunostomy to relieve pain. It is often possible to effect excellent relief of symptoms with maximal conservation of remaining pancreatic functions despite sclerotic obstruction of multiple organ systems. PMID- 2580453 TI - Acute pancreatitis after cardiopulmonary bypass. AB - We have described a spectrum of pancreatic surgery after cardiopulmonary bypass. At one end is a subclinical lesion which was manifested only by elevations in serum isoamylase levels (27 percent of patients) and increased ribonuclease levels (13 percent of patients) in asymptomatic patients followed after cardiac surgery. At the other end is a severe and often lethal necrotizing pancreatitis. Acute necrotizing pancreatitis was found at autopsy in 25 percent of 138 patients who died after cardiac surgery, and it correlated strongly with low output, acute tubular necrosis, and infarction of the liver, spleen, or bowel. It was the principal cause of death in 4 percent of these patients. In addition, 24 percent of 38 nonsurgical patients who died from cardiac failure and hypoperfusion had acute pancreatitis at autopsy, whereas acute pancreatitis was not observed in 55 nonsurgical patients who died without a significant period of low output. Acute pancreatitis was recognized postoperatively in 12 patients (0.2 percent). Three had mild pancreatitis, and all responded well to conservative therapy. In nine patients, fulminant necrotizing pancreatitis developed. Their courses were characterized by significant early postoperative hemodynamic compromise, abdominal distention, ileus, fever, and episodes of late vascular instability associated with hypocalcemia. The diagnosis of pancreatitis was usually missed because of the absence of pain, tenderness and hyperamylasemia. The diagnosis was confirmed at laparotomy in eight patients and at autopsy in one. The only two survivors among the nine with severe cases had aggressive mobilization, debridement, and wide drainage of the necrotic pancreas. We suggest that a mild subclinical injury to the pancreas may occur as a consequence of cardiopulmonary bypass and may progress to severe ischemic necrosis if hypoperfusion follows in the postoperative period, the presentation of necrotizing pancreatitis may be atypical in the cardiac surgical patient and should be considered if nonspecific abdominal symptoms are present, and aggressive debridement and drainage may be the optimal treatment for aggressive forms of this disease. PMID- 2580455 TI - An assay for GDP-D-mannose-4,6-dehydratase. AB - The mechanism of GDP-D-mannose-4,6-dehydratase action with respect to loss of the C5 hydrogen has been established using GDP-D-[5-3H]-mannose as a substrate. This observation has been incorporated into a rapid assay for the enzyme based on the equilibration of 3H with the aqueous medium. PMID- 2580456 TI - Two-dimensional high-performance liquid chromatographic determination of 5 hydroxyindoleacetic acid and homovanillic acid in urine. AB - The biomedically and neurochemically important compounds 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) have been simultaneously determined in human urine after reverse-phase two-dimensional high-performance liquid chromatography. A 10-fold-diluted urine sample (20 microliters) is first separated on a C18 column (30 X 0.39 cm) using an 85% pH 6.0 phosphate buffer/15% methanol solvent system. The elution volume containing both 5-HIAA and HVA (Rt approximately 3 min) is collected. Recoveries (mean +/- SD) for this purification step, which is monitored using fluorometric detection, were usually above 90%. After acidification of the approximately 2 ml collected fraction, 100 microliters is reinjected on a C18 column and separated (Rt: 5-HIAA, 4 min; HVA 5.5 min) using an 80% pH 3.5 phosphate buffer/20% methanol mobile phase. The compounds are determined by flow-through amperometry with absolute detection limits of approximately 25 pg. Both 5-HIAA and HVA are well resolved from other electroactive species present and are easily determined at normal and greatly reduced concentrations in human urine. PMID- 2580457 TI - Immunoblot specificity of monoclonal antibodies assayed against complex extracts. AB - Monoclonal antibodies of known specificity, and target cells of known antigen expression, were used to evaluate the specificity of the immunoblot assay against complex extracts. The antibody panel included 10 previously characterized monoclonals to antigens of known structure: HLA-A,B,C; Ia; and actin. In addition, a commercial reagent was shown to react with HLA chains in immunoblots, and not to cross-react with actin. Target cells known to have strong, weak, or negative expression of the antigens were examined. In all cases, the results were in complete accord with the established properties of the antibodies, antigens, and target cells. For example, HLA bands were detected in lymphoid cells with strong HLA-A,B,C expression, and also in a neuronal cell line with 0.5% of the lymphoid activity. Cytoskeletal cross-reactions, or other unexpected specific bands, were not observed. This work lays a foundation for interpreting immunoblot analyses of monoclonal antibodies to newly defined proteins of complex tissue. PMID- 2580458 TI - Identification and quantification of 5-methoxyindole-3-acetic acid in human urine. AB - A putative pineal metabolite, 5-methoxyindole-3-acetic acid, was quantified in human urine by a gas chromatographic-mass spectrometric method. Excretion of 4.77 +/- 2.25 microgram/day (mean +/- SD) was consistent from each of three normal subjects over 2-4 weeks. Excretion did not vary with regard to menstrual cycle. The daily pattern of excretion bore no relationship to that of 6 hydroxymelatonin, the major metabolite of melatonin, indicating that the major portion of urinary 5-methoxyindole-3-acetic acid does not derive from melatonin. PMID- 2580460 TI - The size and curvature of synapses in the cerebellar cortex of the cat. AB - At the supra Purkinje layer and the subpial level in the molecular layer of lobules V and VI of the cerebellar cortex of the cat, synaptic profiles were measured in ultrathin serial sections treated with either osmium tetroxide (OsO4) or ethanolic phosphotungstic acid (E-PTA). From trace and chord lengths of the intercepts of synaptic profiles the curvature and the mean caliper diameter of the synapse was calculated. In OsO4-material the curvature of synapses yielded an average angle of about 47 degrees and about 36 degrees in E-PTA material. Although these values are contrary to the assumption of a flat disc, which is commonly required in stereological procedures to estimate caliper diameter, the effect of the curvature on the estimation of the mean caliper diameter is limited. This is shown by serial reconstruction analysis of the largest diameter of synapses from maximal arc and chord length measurements at the subpial and supra Purkinje level. The results provide quantitative data concerning synaptic size, curvature and the frequency of intercepts per synapse at the subpial and supra Purkinje level in the cerebellar cortex in OsO4 and E-PTA material. In addition the advantages and disadvantages of E-PTA and osmiumtetroxide staining in quantitative analysis are discussed. PMID- 2580459 TI - Permeability studies of the labyrinth in the guinea pig placenta. I. Perfusion of fixatives and tracers into the fetal circulation. AB - A surgical procedure was developed for cannulation of umbilical vessels in the guinea pig placenta. This approach allows an administration of electron opaque tracers, perfusion of fixatives and injection of corrosion casting compounds with minimal disturbance to the fetus and the placenta. PMID- 2580461 TI - Alterations of immunoreactive somatostatin in thyroid C cells after induced hypercalcemia, hypocalcemia, and antithyroid drug treatment. AB - In order to elucidate the functional significance of somatostatin in thyroid C cells, the alterations of immunoreactive somatostatin in the cells were investigated under various experimental conditions, i.e., hypercalcemia, hypocalcemia, and antithyroid drug treatment. Guinea pigs and rabbits, in which almost all C cells reveal the intense immunoreaction for somatostatin in addition to calcitonin, were used as experimental animals. After chronically induced hypercalcemia, somatostatin immunoreactivity conspicuously diminished coinciding with the decrease of calcitonin; somatostatin as well as calcitonin was responsive to induced hypercalcemia. After hypocalcemic tetany induced by injection of Escherichia coli L-asparaginase, C cells exhibited very intense immunoreactions for both calcitonin and somatostatin. After chronic treatment of ethylenethiourea, immunoreaction of somatostatin in C cells was the same as that of calcitonin. That is, when immunoreactivity for calcitonin remained unchanged, immunoreactivity for somatostatin was also intensive. However, when immunoreaction of calcitonin became very weak, the reaction of somatostatin was also weak. Thus, in all experimental conditions examined the alterations of immunoreactive somatostatin in C cells completely coincided with those of calcitonin. It seems likely that somatostatin in thyroid C cells exerts the synergistic effect on calcitonin action. PMID- 2580462 TI - Clinical implications of the modulated receptor hypothesis: local anesthetics and the heart. PMID- 2580464 TI - [Severe peranesthetic anaphylactic accidents]. PMID- 2580463 TI - Mechanism for bupivacaine depression of cardiac conduction: fast block of sodium channels during the action potential with slow recovery from block during diastole. AB - The effects of bupivacaine and lidocaine on cardiac conduction were compared in guinea pig ventricular muscle. Membrane potential was controlled using a single sucrose gap voltage clamp technique, and the maximum upstroke velocity of the action potential (Vmax) was used as an indicator of peak sodium current. Bupivacaine blocked cardiac sodium channels in a time- and voltage-dependent fashion. Although bupivacaine has a low affinity for rested and activated sodium channels, it avidly blocks inactivated channels (Kd = 9 X 10(-7) M). Bupivacaine associated channels do not conduct and have their voltage dependence of inactivation shifted by about 33 mV to more negative potentials. At bupivacaine concentrations above 0.2 micrograms/ml, a substantial fraction of the channels become blocked during the cardiac action potential, while recovery from block during diastole proceeds relatively slowly with a time constant (tau) of 1,557 +/ 304 ms (n = 8). Thus, bupivacaine blocks sodium channels in a fast-in-slow-out fashion, and substantial block accumulates at 60-150 beats/min. In comparison, 5 10 micrograms/ml lidocaine also blocks a substantial fraction of channels during the action potential, but diastolic recovery from block is more rapid (tau = 153.8 +/- 51.2 ms, n = 4). Thus, lidocaine blocks channels in a fast-in-fast-out fashion. Consequently, even at toxic doses of lidocaine (i.e., 10 micrograms/ml), little accumulation of block occurs at normal heart rates. Sodium channel block by bupivacaine can be minimized by reducing heart rate, hyperpolarization, and shortening of action potential duration. However, alteration of these variables over clinically applicable ranges does not produce marked changes in bupivacaine effect. Our results provide a possible explanation for the clinical observation that when bupivacaine accidently gains access to the general circulation, cardiac conduction can be depressed seriously and such depression may be difficult to reverse. PMID- 2580465 TI - Serum amylase isoenzyme alterations in acute abdominal conditions. AB - To determine the accuracy of the serum amylase in identifying a pancreatic source, amylase isoenzymes were determined prospectively in 65 patients initially evaluated with a complaint of abdominal pain and associated hyperamylasemia. Isoenzyme patterns were demonstrated by an electrophoretic technique, and the results were correlated with clinical diagnoses. Patients were divided into two diagnostic groups. Group I consisted of 42 patients with clinical findings suggesting pancreatitis. P-type isoenzymes were normal or elevated in 31 of these patients (74%), and s-type isoenzymes were normal or elevated in 11 (26%). Group 2 consisted of 23 patients with abdominal pain attributed to causes other than pancreatitis. Four patients (17%) had elevation of p-type isoenzymes, and 19 patients (83%) had predominantly s-type patterns. We conclude that amylase isoenzymes cannot determine unequivocally the cause of hyperamylasemia, but they can enhance the diagnostic specificity of the serum amylase. Elevated serum amylase with a predominant p-type pattern suggests pancreatic disease; elevation of s-type isoenzymes suggests but is not conclusive for, diagnoses other than pancreatitis. Hyperamylasemia with a normal isoenzyme pattern occurred in a few patients in both groups, and it was nondiagnostic. PMID- 2580466 TI - Chronic relapsing pancreatitis in childhood. AB - Chronic intermittent abdominal pain in childhood, reported to afflict nine to 12 per cent of all children, is an enigma of such magnitude that more than 30 per cent of these patients reach adulthood with persistent problems and no definitive diagnosis. This report discusses 20 children with such pain (9 girls and 11 boys) in whom routine diagnostic evaluation failed to identify the etiology. Selected special diagnostic studies and considerable suspicion for chronic pancreatitis prompted surgical intervention in three patients. Two were unsuspected and identified at celiotomy as having pancreatitis. The morphine-neostigmine evocative test, modified in some cases to confirm its usefulness, was helpful, accurate, and definitive in all 13 patients on whom it was used. Eighteen patients were confirmed surgically to have pancreatic disease, and two patients are unoperated with continued pancreatic pain. Ductal pathology was believed present in all. Of 18 patients operated, 11 patients are asymptomatic, five patients are improved, and two patients are considered failures 6 months to 10 years following surgery. PMID- 2580467 TI - Diagnostic assays in acute pancreatitis. A study of sensitivity and specificity. AB - The sensitivity and specificity of five assays used to diagnose acute pancreatitis were studied: two amylase assays; one lipase; one trypsinogen; and one pancreatic isoamylase. Thirty-nine patients with acute pancreatitis were compared to 127 controls with abdominal pain. Using the upper limit of normal both amylase assays appeared sensitive but somewhat nonspecific (specificities of 88.9% and 86%, respectively). The trypsinogen and pancreatic isoamylase assays were also relatively nonspecific (specificity of 82.8% and 85.1%). Most nonspecific elevations occurred between a one- and twofold elevation of each assay. Lipase, however, maintained excellent specificity (99%) at its upper limit of normal. If the level of best cutoff is used instead (the level that best enhances sensitivity and specificity), the specificities of both amylase assays, as well as the trypsinogen and pancreatic isoamylase assays, exceed 95%. At the best cutoff level, trypsinogen maintains a qualitative advantage in sensitivity over lipase or pancreatic isoamylase (97.4% as compared to 86.5% and 84.6%). PMID- 2580468 TI - MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. AB - Between April 1981 and May 1984, 61 patients with advanced diffuse large-cell lymphoma completed treatment with MACOP-B (methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin), an innovative pilot chemotherapy program emphasizing weekly treatment, antibiotic prophylaxis, daily corticosteroid treatments, and brief duration (12 weeks). Fifty-one patients (84%) achieved a complete response and 10 patients (16%) had a partial response. Over a median follow-up after treatment of 23 months, the actuarial overall survival for the entire group has been 76%; for complete responders the relapse-free survival has been 90%. Toxicity was modest with one treatment-related death and seven episodes of serious infection. The most frequent toxicity was mucositis. Thus, MACOP-B is an effective treatment for large-cell lymphoma that can be delivered in 12 weeks with an acceptable incidence of toxicity. This regimen can achieve results similar and possibly superior to those of other presently used regimens of longer duration. PMID- 2580469 TI - Endoscopic neodymium-YAG laser palliation of nonresectable esophageal malignancy. AB - Seven men and five women with nonresectable esophageal carcinoma were treated endoscopically with the neodymium-YAG (yttrium-aluminum-garnet) infrared laser. Before laser fulguration, tumors were dilated directly with metal olive dilators. Before treatment, mean tumor length was 5 cm with luminal occlusion averaging more than 80%. After a mean of 3.3 treatment sessions spanning 18.5 days, all patients had substantial immediate palliation. Continued symptomatic relief was noted during follow-up (mean, 83 days; range, 8 to 206 days). PMID- 2580470 TI - How much can we know about acute pancreatitis? PMID- 2580471 TI - Applications of monoclonal antibodies to neuroscience research. AB - The preceding discussion documents the diverse ways in which monoclonal antibodies have contributed to neuroscience research. They provide highly specific reagents to membrane-associated proteins, such as pumps, channels, receptors, and cell-adhesion molecules, that are useful for purifying these proteins, studying their structures at high resolution, and mapping their distributions. In many cases, the specific reagents were obtained using only partially purified antigens. Monoclonal antibodies to cytoskeletal proteins, organelles, and protein kinases have revealed that specific molecules are concentrated in anatomically distinct regions of the cell. A protein kinase has been shown to be a major postsynaptic constituent in many synapses. Individual proteins, such as actin, tubulin, and calmodulin appear to have different antigenic epitopes shielded in different parts of the cell. Monoclonal antibodies have provided a diversity of cell-type-specific reagents in both vertebrate and invertebrate nervous systems. They seem likely to be useful in identifying functionally related subpopulations of neurons and describing neural cell lineages. They will also serve to identify molecules that are important in regulating cell migration in the cerebellum, in marking cell position in the retina, and directing axon growth. This review also documents many purposes for which monoclonal antibodies are poorly suited or must be used with caution: A monoclonal antibody to a protein does not always reveal every place where that molecule is located. Pre- or post-translational microheterogeneity can expose different epitopes on the protein, such as may occur on the Na+-channel. Other proteins within the cell may shield antigenic sites on proteins such as calmodulin. Monoclonal antibodies can bind to epitopes on unrelated molecules (Nigg et al 1982, Lane & Koprowski 1982). This is revealed in some cases as multiple bands on immunoblots. Some cross-reactivity, however, may have a functional basis. For example, structural homology is clearly the basis for the antigenic epitopes that are shared among the five classes of intermediate filaments (Pruss et al 1981). The epitope that appears to be shared between the muscarinic and alpha 1-adrenergic receptors may be conserved because the two receptors modulate common effectors. The cross-reactivity between these receptors was only recognized because very specific and sensitive assays exist for each. It is quite possible that these same antibodies also bind sites on many other types of receptors. Mapping the distribution of this epitope may therefore have little relationship to the actual distribution of the muscarinic receptor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2580472 TI - Phototransduction in vertebrate rods. PMID- 2580473 TI - Mobility and localization of proteins in excitable membranes. PMID- 2580474 TI - Clonal analysis and cell lineages of the vertebrate central nervous system. PMID- 2580475 TI - [Tentative classification of the ultrasound symptomatology of the prostate by an anatomo-ultrasonic comparison of 34 cases]. AB - Ultrasound and histological sections were taken of 34 prostate units removed from fresh cadavers. Ultrasonography seems to raise more problems than it solves; only 73% of the normal prostates were homogeneous under ultrasound. Ultrasonography visualized nodular structures requiring biopsy in 71% of the cases of prostatic adenoma. There were too few cases of malignant tumors in the sample to warrant a conclusion. They were highly evolved. Ultrasonography gave strong grounds for suspicion, but they could be easily diagnosed clinically. PMID- 2580476 TI - [Contribution of suprapubic ultrasound in prostatic hypertrophy]. AB - After describing the technique, the authors recall the ultrasound anatomy of the prostate with the symmetrical echoes given by the seminal vesicles, the vas deferens and the ejaculatory ducts, which often allow a distinction to be made between the cranial and caudal portions of the prostate. Calculation of the volume (normally under 20 cm3) measures the enlargement (useful in determining the choice of approach), using the formula (Formula: see text) Ultrasound also often gives some idea of the nature of the lesion. The main distinction between an adenoma and a carcinoma is the fact that the adenoma is normally confined to the cranium. Carcinomas are generally asymmetrical, and their structure is non echogenic, giving coarse echoes. Chronic prostatis, on the other hand, leads to the existence of symmetrical hyper-echogenic areas, sometimes calcified. The main contribution of suprapubic ultrasound is the information it provides concerning the repercussions on the urinary tract (residue, straining bladder, repercussions on the kidney). It can also be used to monitor developments. PMID- 2580477 TI - SSPE treated with isoprinosine: immunopathological observations. PMID- 2580478 TI - Lack of accumulation of exogenous adenylyl dihydrostreptomycin by whole cells or spheroplasts of Escherichia coli. AB - Accumulation of purified adenylylated dihydrostreptomycin (DHS-AMP) was examined in two strains of Escherichia coli. E. coli JSRO-N was plasmid free and aminoglycoside (AG) susceptible; E. coli JSRO-N(pSAD1) contained a plasmid encoded AG adenylyltransferase which modifies DHS and streptomycin and confers resistance to both of these drugs. Although both whole cells and spheroplasts of JSRO-N accumulated free DHS, we were not able to demonstrate uptake of DHS-AMP by this strain. Whole cells and spheroplasts of JSRO-N(pSAD1) accumulated DHS at a much slower rate than that observed in JSRO-N. This was presumably due to the activity of the adenylyltransferase in JSRO-N(pSAD1). However, this low rate of accumulation of DHS was still higher than the uptake of DHS-AMP by either JSRO-N or JSRO-N(pSAD1). Thus, the rate of accumulation of DHS-AMP was even lower than that of DHS during the slow, initial, energy-dependent phase of AG uptake seen in JSRO-N(pSAD1). We also found that when either JSRO-N or JSRO-N(pSAD1) was incubated with barely inhibitory or subinhibitory concentrations of DHS, rapid uptake of DHS could be stimulated by the addition of an inhibitory concentration of another AG, such as amikacin. Uptake of DHS-AMP could not be similarly enhanced by the addition of amikacin. Our results indicate that DHS-AMP is not accumulated by whole cells or spheroplasts of E. coli. These results are consistent with the postulated intracellular location of AG-modifying enzymes. PMID- 2580479 TI - Diffusion of beta-lactam antibiotics through the porin channels of Escherichia coli K-12. AB - Diffusion rates of various beta-lactam antibiotics through the OmpF and OmpC porin channels of Escherichia coli K-12 were measured by the use of reconstituted proteoliposomes. The results can be interpreted on the basis of the gross physicochemical properties of the antibiotics along the following lines. (i) As noted previously (Nikaido et al., J. Bacteriol., 153:232-240, 1983), there was a monotonous dependence of the penetration rate on the hydrophobicity of the molecule among the classical monoanionic beta-lactams, and a 10-fold increase in the octanol-water partition coefficient of the uncharged molecule decreased the penetration rate by a factor of 5 to 6. (ii) Compounds with exceptionally bulky side chains, such as mezlocillin, piperacillin, and cefoperazone, showed much slower penetration rates than expected from their hydrophobicity. (iii) The substituted oxime side chain on the alpha-carbon of the substituent group at position 7 of the cephem nucleus decreased the penetration rate almost by an order of magnitude; this appears to be largely due to the steric effect. (iv) The presence of a methoxy group at position 7 of the cephalosporins also reduced the penetration rate by 20%, probably also due to the steric hindrance. (v) Zwitterionic compounds penetrated very rapidly, and the correlation between the rate and hydrophobicity appeared to be much weaker than with the monoanionic compounds. Imipenem showed the highest permeability among the compounds tested, presumably due, at least in part, to its compact molecular structure. (vi) Compounds with two negative charges penetrated more slowly than did analogs with only one negatively charged group. Among them, only moxalactam, ceftriaxone, and azthreonam showed penetration rates corresponding to, or higher than, 10% of that of imipenem. PMID- 2580480 TI - Antimyocarditic activity of the guanine derivative BIOLF-70 in a coxsackievirus B3 murine model. AB - Prophylactic administration of a nontoxic dose of 9-[[2-benzyloxyl-1 (benzyloxymethyl)ethoxy]methyl]-6-chlo roguanine (BIOLF-70) to mice reduced the number of myocarditic lesions induced by coxsackievirus B3 (CVB3). BIOLF-70 exhibited minimal antiviral activity against CVB3 in HeLa cells and murine neonatal skin fibroblasts and minimally reduced CVB3 yields in heart tissues. The drug had no effect on serum anti-CVB3 neutralizing antibody titers and did not induce the production of interferon. Flow microfluorometric analyses of splenic lymphocytes taken from BIOLF-70-treated, CVB3-inoculated mice at 7 days postinoculation showed that the proportion of T lymphocytes was increased, as measured by fluorescent staining of Thy-1 and Lyt-2 surface markers, compared with the proportion of T lymphocytes in splenic cells from virus-inoculated or BIOLF-70-treated or normal groups of mice. Splenic lymphocytes from BIOLF-70 treated, CVB3-inoculated mice showed reduced cytotoxic activity against CVB3 infected target fibroblasts. Splenic cells from BIOLF-70-treated, CVB3-inoculated mice had slightly higher natural killer cell activity than did those from the other three groups of mice, which had comparatively similar levels of natural killer cell activity. The data suggest that BIOLF-70 exerts antimyocarditic activity perhaps by some antiviral activity in heart tissues and by immunomodulatory mechanisms which appear to involve T suppressor or T cytotoxic lymphocyte subpopulations and natural killer cells. PMID- 2580482 TI - Activities of arabinosyladenine monophosphate and 9-(1,3-dihydroxy-2 propoxymethyl)guanine against ground squirrel hepatitis virus in vivo as determined by reduction in serum virion-associated DNA polymerase. AB - Treatment of chronic ground squirrel hepatitis virus infection with arabinosyladenine monophosphate at 20 mg/kg per day for 3 weeks caused marked decreases in serum virion-associated DNA polymerase concentrations in three of five squirrels. Statistically significant but less dramatic decreases in enzymatic activity were noted in two of six squirrels treated with 50 mg of 9 (1,3-dihydroxy-2-propoxymethyl)guanine per kg per day. After therapy, DNA polymerase activities rose to pretreatment levels. PMID- 2580481 TI - Mechanism of action and selective toxicity of ascamycin, a nucleoside antibiotic. AB - An unidentified Streptomyces sp. produces two nucleoside antibiotics, ascamycin and its dealanyl derivative. In contrast to the broad antibacterial activity of dealanylascamycin against various gram-negative and gram-positive bacteria, ascamycin showed selective toxicity against Xanthomonas citri and X. oryzae. Both ascamycin and dealanylascamycin inhibited the protein synthesis of X. citri, but only dealanylascamycin inhibited that of Escherichia coli. In cell-free systems from E. coli and X. citri, both antibiotics, at ca. 0.04 micrograms/ml, inhibited the polyuridylate-directed synthesis of polyphenylalanine by ca. 50%. These data suggest that ascamycin cannot permeate the bacterial membrane. The dealanylating activity toward ascamycin was found only on the cell surface of bacteria susceptible to ascamycin. Dealanylascamycin must then have been transported into cytoplasm, where it inhibited protein synthesis. PMID- 2580483 TI - Role of interferon in the resistance of C3H/HeJ mice to infection with herpes simplex virus. AB - C3H/HeJ mice known to be defective in their responses to bacterial lipopolysaccharides, are more resistant to infection with herpes simplex virus (HSV) than the closely related strain C3HeB/FeJ. The increased resistance is reflected in higher early local interferon titers after HSV infection. However, NK cell activation by HSV is not correlated with resistance, since the NK cell response of C3H/HeJ mice was significantly lower than that of the control strain. PMID- 2580484 TI - A photosystem II-phycobilisome preparation from the red alga, Porphyridium cruentum: oxygen evolution, ultrastructure, and polypeptide resolution. AB - The photosystem II-phycobilisome preparation, isolated by lauryldimethyl amine oxide treatment, had a greatly reduced chlorophyll content, with an average ratio of 90 chlorophyll a/phycobilisome as compared to approximately 1200 Chl/phycobilisome in unfractionated thylakoids. P700 was not detected in the particles. By electron microscopy the preparations were relatively homogeneous and were generally devoid of chloroplast membranes. In negatively stained preparations phycobilisome particles were seen often in clusters of two and three, probably due to retention of hydrophobic thylakoid fragments. The preparation was deficient in photosystem I chlorophyll complexes, but enriched in polypeptides of 85 to 92, approximately 43, and approximately 26 kDa, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 43- and 26-kDa polypeptides are attributable to the PS II core and the oxygen evolving complex, respectively. PMID- 2580485 TI - [Chemical modification of anti-cancer drugs to increase their affinity to tumor antigens]. AB - In order to increase the selective localization of anti-cancer drugs to the target tumor cells, polyclonal or monoclonal anti alpha-fetoprotein antibody (aAFP) was conjugated with anti-cancer drugs such as daunomycin (DM), adriamycin (AM) and mitomycin C (MMC) by chemical modification. Dextran (Dex) or poly L glutamic acid (PLGA) was used to bind aAFP with DM (AM) as an intermediate drug carrier. For the conjugation of aAFP with MMC, a direct binding method through the aziridine ring of the activated MMC derivative or an indirect binding method through serum albumin as an intermediate drug carrier was employed. These conjugates caused greater inhibition of both in vitro and in vivo tumor growth of AFP-producing target tumor cells than did a mixture of aAFP and anti-cancer drugs or a simular conjugate of these drugs with normal horse immunoglobulin. AFP has high affinity to unsaturated fatty acids (UFA) such as arachidonic acid (C20:4) and so on. The antitumor effect of UFA-DM conjugate was also assessed using AFP producing rat ascites hepatoma cells. It was found that UFA-DM conjugated showed highly selective cytocidal effects against the hepatoma cells. PMID- 2580487 TI - [Arterial infusion method: its theory and clinical application--dosage and regimen]. AB - The special feature of the arterial infusion method is that, when an anticancer agent is given, a high concentration of the drug is distributed through the nourish arterial system to the neoplasm. However, should the drug flow back to the heart and enter the second circulation system, the same dynamics hold as do in the venous route approach. Thus, using this feature, the suitable anticancer agent must be selected and the dose and regimen determined. Recently, continuous arterial infusion of 5-FU, MTX and other agents, arterial infusion of MMC and ADM over a given time course, plus microcapsulation of anticancer agents or improved chemotherapy for possible embolization, have been used to deal with embolisms. The most remarkable effects have been obtained in liver carcinoma among others. Rescue with antidotes to counter side effects of using the arterial route is relatively easy. There are agents suitable for arterial infusion among BRM, and favorable clinical applications are expected. PMID- 2580486 TI - [Continuous venous infusion in cancer chemotherapy]. AB - The benefits of continuous venous infusion of anti-cancer agents including increased antitumor efficacy or decreased toxicity was discussed from the view point of the mechanism of action and pharmacokinetics of the drugs. Pulmonary toxicity of bleomycin, cardiotoxicity of adriamycin and myelosuppression of 5 fluorouracil may be reduced by continuous infusion. Antitumor efficacy may be increased by continuous infusion in the case of bleomycin, 5-fluorouracil and cytosine arabinoside. Thus these drugs may show an improvement in the therapeutic index when given as a continuous infusion. PMID- 2580488 TI - [Radiochemotherapy of head and neck cancers: dose reduction through the combination of cisplatin, bleomycin and tegafur]. AB - Twenty-four cases of squamous cell carcinomas of the larynx and maxillary sinus were irradiated with or without cisplatin during a period from April 1973 through March 1984. Both bleomycin in oil and tegafur were administered irrespective of cisplatin. Therapeutic effectiveness was critically evaluated by means of serial biopsy and/or surgery. Radiotherapy alone could not bring about negative conversion of the biopsies, but ultimate negative conversion was observed in 18 out of the 24 cases when chemotherapeutics were appropriately combined. The five positives underwent surgery. In the cases of maxillary cancer, mixed infections appeared to interfere with the curative effectiveness of the radiochemotherapy. A resulting dosage reduction of 15Gy was observed in radiotherapy for negative conversion and one of 10mg for bleomycin as a result of incorporation of cisplatin. PMID- 2580490 TI - [Conventional and differential staining technics for observation of mammalian chromosomes]. AB - Conventional staining techniques such as Giemsa, orcein and carmine and several differential staining techniques for the observation of mammalian chromosomes are described in this chapter. The differential staining techniques are described by classifying them into two groups; one group consists of banding stainings involving quinacrine (Q-band) and Giemsa (G-band), while the other involves several differential stainings for observation of the inner-organization of chromosomes, such as the constitutive and facultative heterochromatins, the nucleolar organizer regions and the centromeric regions. PMID- 2580489 TI - [Successful treatment of mediastinal seminoma with combination chemotherapy of cis-diamminedichloroplatinum (CDDP), vinblastine (VBL), and bleomycin (BLM)]. AB - Complete response (CR) has been achieved in a case of advanced mediastinal seminoma using PVB therapy (CDDP, VBL, BLM). A 21-year-old man visited our department with the complaint of superior vena cava syndrome. Chest X-ray film, ultrasonography and CT scan revealed a large anterior mediastinal mass. Histological proof of mediastinal seminoma was obtained by needle biopsy. The patient was treated with a combination chemotherapy, consisting of CDDP, VBL and BLM according to Einhorn's PVB regimen. After three courses of this regimen, complete disappearance of the tumor was obtained. The patient underwent further radiation treatment (Linac: 4,000 rad), as a salvage therapy, at the anterior mediastinum, and has since been doing well without any sign of recurrence for a follow-up period of nine months. PMID- 2580491 TI - Outcome for children subject to non-accidental injury. PMID- 2580492 TI - Carcinoid syndrome: an unusual cause of diarrhoea. AB - A 9 year old girl underwent laparotomy because of intermittent diarrhoea, present since infancy. Histology of a mass at the head of pancreas and multiple hepatic nodules suggested an apudoma. Plasma serotonin and urinary excretion of 5 hydroxy indole acetic acid were raised. The child is asymptomatic four years after diagnosis. PMID- 2580493 TI - Phototherapy of urticaria pigmentosa: clinical response and changes of cutaneous reactivity, histamine and chemotactic leukotrienes. AB - Ten patients with moderate to very severe urticaria pigmentosa were studied for the therapeutic effect of photochemotherapy (PUVA; six adults) and selective ultraviolet phototherapy (SUP; four adolescents). Despite a high mean PUVA dosage (138.6 +/- 63.4 J/cm2), only two patients had a very good response, while three had a good response and one had a fair response. On the reduction of the frequency of treatments, the symptoms gradually recurred, and several months after the discontinuation of therapy, the clinical status had reached the level prior to PUVA. The results with SUP were even less encouraging. A number of biophysical and biochemical parameters of the skin were studied in five patients before PUVA treatment, immediately after several months of PUVA treatment and again 5 months after the discontinuation of PUVA treatment. Weal and erythema reactions to intracutaneous skin tests remained unchanged after PUVA, while wealing with topically applied dimethylsulfoxide (DMSO) decreased. Transepidermal water loss was markedly reduced over DMSO weals. Histamine levels, which were elevated in lesional but not in normal skin, dropped with PUVA treatment, but after the discontinuation of treatment, they increased again in the lesions. On reverse-phase high-performance liquid chromatography, two main chemotactic factors, leukotriene B4 and 5-HETE, were identified in lesional skin. Chemotactic activity was elevated in both lesional and uninvolved patient skin, reached normal levels at both sites after PUVA and maintained these low levels for several months after the discontinuation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580494 TI - Effect of crude coal tar in the mouse-tail model of psoriasis. AB - A histological comparison was made between normal mouse tails and those treated with crude coal tar, and the effect of crude coal tar on the keratin profile of the living cells of treated animals was examined. The prophylactic effect of crude coal tar on the neonatal mouse tail is described. The variation in the anatomical site of prekeratin of the dorsal and tail epidermis of the mouse is reported. These results are discussed with reference to the use of the mouse tail as a model for screening drugs for the treatment of psoriasis. PMID- 2580495 TI - Myelin-associated glycoprotein in neurogenic tumours of the skin: an immunohistological study using Leu-7 monoclonal antibody. PMID- 2580496 TI - On the nature of dextran sulphate binding of antibodies to DNA in sera from patients with systemic lupus erythematosus (SLE). PMID- 2580499 TI - Thrombocytopenia following sustained-release procainamide. AB - Procainamide hydrochloride-induced thrombocytopenia has infrequently been reported in the past. We report six cases of thrombocytopenia following the administration of the sustained-release form of procainamide. Three of these cases had platelet counts of less than 15,000/microL. The mean time to onset of thrombocytopenia from drug administration was 40 days (range, nine to 71 days). The mean time until normalization of the platelet counts after the drug therapy was stopped was 7.8 +/- 3.1 days (range, four to nine days). Oral prednisone therapy had little apparent benefit. The thrombocytopenia was not part of a systemic lupus erythematosus syndrome. We believe that thrombocytopenia is an important side effect of sustained-release procainamide therapy. PMID- 2580500 TI - Is serum amylase an obsolete test in the diagnosis of acute pancreatitis? PMID- 2580498 TI - Echinococcus granulosus: failure of the eosin-exclusion test to demonstrate death of protoscoleces. PMID- 2580497 TI - Temephos (Abate) metabolism and toxicity in rats. PMID- 2580501 TI - Serum tests for pancreatitis in patients with abdominal pain. AB - Though the serum total amylase test has been used for the diagnosis of pancreatitis for over 50 years, both its clinical sensitivity and specificity are far from perfect. We first present the results of serial serum total amylase, pancreatic isoamylase, lipase, and immunoreactive trypsin tests in nine patients during the week after their admission to the hospital with a diagnosis of acute pancreatitis, and then compare the serum total amylase, lipase, and immunoreactive trypsin levels in the initial serum submitted for amylase analysis from 100 patients because of the clinical suspicion of acute pancreatitis. In the former group of patients, the serum total amylase test was the least sensitive of the tests for pancreatitis after the first hospital day. In the latter group of patients, the largest discordance was found in patients with elevated serum total amylase levels, but normal lipase and immunoreactive trypsin levels. In 90% of these discordant cases, the elevation of serum total amylase was due to salivary amylase, yielding a maximum clinical specificity of only 71% for serum total amylase. Based on these data, we conclude that alternate tests deserve careful consideration as replacements for the serum total amylase test. PMID- 2580502 TI - Identification of human megakaryocytes with rhodanile blue. AB - Using the oxazine dye rhodanile blue, large typical megakaryocytes and small megakaryocytes (micromegakaryocytes) from the bone marrows of normal persons, and from patients with a variety of preleukemic disorders, acute lymphoblastic and nonlymphoblastic leukemia, chronic granulocytic leukemia, and idiopathic thrombocytopenic purpura as an example of nonmalignant but abnormal megakaryocytopoiesis, showed intense pink staining of the cytoplasm. This pink metachromasia was not obliterated by prior digestion with either diastase or ribonuclease, but was markedly diminished or obliterated by preincubation with hyaluronidase, suggesting that the stain may detect a high content of acid mucopolysaccharides in megakaryocytes. Since the stain is simple, direct, and reproducible, it may represent a useful addition to the cytochemistry of megakaryocytes and complement the more complex immunologic techniques available currently. PMID- 2580503 TI - Relationship of reticulocyte age to polychromasia, shift cells, and shift reticulocytes. AB - Polychromatophilic erythrocytes on Wright-stained blood smears represent young reticulocytes. Ratios of polychromatophilic cells to total reticulocyte counts have been used to estimate marrow response to erythropoietin stimulation. These ratios, however, require both accurate counts of polychromatophilic cells on Wright-stained blood smears and reticulocytes on supravitally stained blood smears. Data from this study indicated that reticulocytes of Heilmeyer groups I, II, and III best represent polychromatophilic cells. Group III reticulocytes, however, were found in normal circulation and were difficult to distinguish from group IV reticulocytes. Groups I and II were not found in normal circulation and were easily identified on routine reticulocyte preparations. The term "shift reticulocyte" is proposed for reticulocytes of groups I and II only. The present study suggests that the "shift reticulocyte count," expressed as percent of 100 reticulocytes, is a more useful indicator of marrow response to anemia than total reticulocyte counts. PMID- 2580504 TI - Identification of foam cells in human atherosclerotic lesions as macrophages using monoclonal antibodies. AB - Four monoclonal antibodies against human monocyte/macrophage epitopes were used in an immunoperoxidase procedure to identify foam cells in atherosclerotic plaques from human aortas and coronary arteries. All antibodies gave positive reactions with the majority of foam cells observed in fatty streaks and advanced atheromas. Immunoperoxidase staining correlated with oil red O and nonspecific esterase-positive areas. Use of the immunohistochemical technique on Bouin's fixed, paraffin-embedded tissue gave good results that afforded better localization and cell morphology than observed with frozen sections. In addition to the identification of the majority of foam cells as monocytic in origin, the technique described allowed visualization of membrane-bound extracellular droplets that were monocyte derived within necrotic cores of atheromas, indicating a contribution by dead macrophages to the lipid of atherosclerotic plaques. PMID- 2580505 TI - Immunohistology of human thymomas. AB - We analyzed lymphocyte surface markers in seven thymomas. In six mixed thymomas, the staining patterns were similar for T11, OKT8, OKT6, OKT4, Coulter clone T4, and Leu 3a/3b. Staining patterns for Ia and keratin showed a dendritic pattern. Occasional S 100-positive interdigitating dendritic cells were identified. In three patients with associated myasthenia gravis, no significant differences in staining patterns were identified. A different pattern was seen in a patient with hypogammaglobulinemia, red blood cell aplasia, and a spindle cell thymoma: T11-, T8-, and T6-positive cells each comprised 70% to 80% of the tumor; but, cells of the helper/inducer phenotype differed when measured with OKT4 antibody (0%) vs Coulter clone T4 antibody (60%) and Leu 3a/3b (60%). This unusual phenotype, which was present on both tumor cells and peripheral T cells, appears related to the antigenic polymorphism of the T4 antigen and is believed to have no functional significance. Importantly, this discrepancy among commercial antibodies has significant implications in the general use of these reagents in clinical evaluations. PMID- 2580506 TI - Postnatal changes in calcium and amylase of rat salivary glands, including calcium changes with senescence. AB - Postnatal changes occur in glandular Ca concentration of rat parotid and submandibular glands. At 4 days of age, Ca concentration was low in both glands (only one-third to one-half that of adults) and increased gradually with age. The pattern of change was generally similar for male and female rats, but in submandibular gland, adult levels of 9-10 m-equiv./kg were reached by weaning, whereas for parotid gland, a gradual increase in Ca concentration occurred with adult levels of 9-10 m-equiv./kg reached by 7 weeks of age. The pattern of change was the same whether Ca concentration was expressed per kg wet or dry weight albeit water content changed with age. The changes in Ca concentration of parotid paralleled the age-associated increases in amylase activity of parotid gland. Amylase activity of submandibular gland was much less than that of parotid and similarly low at all ages examined, and did not parallel the age-associated increases in Ca concentration. The regulatory role of the sympathetic innervation on glandular Ca concentration was examined by effecting surgical denervation of parotid and submandibular glands at 8 days of age, and then determining Ca concentration of the denervated glands at 32 days. A three-fold increase in Ca concentration, similar to that following acute sympathectomy in adults, occurred in submandibular gland but no change was seen in parotid. An unexpectedly high concentration of Ca was also found in submandibular (but not parotid) gland of old rats. PMID- 2580507 TI - Choroidal reaction and vascular repair after chorioretinal photocoagulation with the free-running neodymium-YAG laser. AB - The morphologic effects of the neodymium-YAG laser working in the free-running mode on the choroid of pigmented rabbit eyes have been studied by electron microscopy. Two different mechanisms closing the choroidal vessels were found. The larger vessels of the vascular lamina were closed by platelet aggregation, while within the choriocapillaries a network of fibrin could be observed. The endothelial cells of the vessels were found to be damaged in capillaries as well as in the larger vessels. Within the irradiated area, a revascularization process takes place, expanding from the border towards the center. The process begins a few days after treatment and continues for more than four months. The process of neovascularization is described in detail. Beside fibroblasts, cells could be found that were active in producing elastic fibers. PMID- 2580509 TI - A study of cartilaginous nodules in the lungs of domestic poultry. AB - A high incidence of cartilaginous nodules was found in the lungs of broiler chickens. The incidence was higher in broilers fed ad libitum than in broilers fed a restricted amount of food. A much lower incidence of nodules was found in leghorn-type chickens, turkeys, ducks, and geese. It was theorized that the nodules may develop from embolic chondrocytes arising from abnormal cartilage, but no correlation could be found between lesions in the cartilage of the broilers and the presence of nodules in their lungs. PMID- 2580508 TI - Intranasal dermal analogue tumor (membranous basal cell adenoma). Ultrastructure and immunohistochemistry. AB - To our knowledge, this is the first case of an intranasal monomorphic salivary gland adenoma (dermal analogue type) arising in a man exhibiting the salivary gland-skin adnexal tumor diathesis. Ultrastructurally, this tumor is composed of cells displaying squamous, secretory, luminal, and, very rarely, myoepithelial differentiation. Additionally, this is the first ultrastructural demonstration of intralobular Langerhans' cells in a dermal analogue tumor from any site. These Langerhans' cells can be demonstrated histologically by S-100 protein immunostaining. Epithelial tumor cells per se display no glial fibrillary acidic protein immunoreactivity, but rare epithelial cells stain faintly for S-100 protein. These findings seem to be distinct from pleomorphic adenoma and adenoid cystic carcinoma, the principal histologic differential diagnosis. PMID- 2580510 TI - Cases from the aerospace medicine residents' teaching file. Case #4. An airline captain with a presenting sign of some premature ventricular contractions. AB - An airline captain with a presenting sign of some premature ventricular contractions. The clinical presentation, evaluation, and diagnosis of the pilot are discussed. The aeromedical disposition and prognosis of this patient are provided. PMID- 2580511 TI - Influence of starvation and total protein deprivation on cardiac mRNA levels. AB - The effect of starvation and of protein-deprivation on the extractable amount of cardiac mRNA was investigated in male rats. Cardiac mRNA was determined by either (a) isolation of cardiac mRNA by SDS-Phenol/oligo-dT-cellulose, or by (b) hybridization of cardiac mRNA to 3H-Poly(U). During starvation (1-6 days) the extractable amount of cardiac microsomal RNA decreased from 870 micrograms/g heart (controls) to 606 micrograms/g (3 days) and to 547 micrograms/g (6 days), the extractable amount of mRNA fell from 28.6 micrograms/g heart (controls) to 18.7 micrograms/g (3 days) and to 14.5 micrograms/g (6 days). When a normocaloric but protein-deficient diet was fed, the decreases in cardiac microsomal RNA and mRNA were qualitatively similar, but slightly less severe. An analysis of the intracellular distribution of cardiac microsomal RNA and mRNA in the hearts of normal animals and of animals starved or fed a protein-deficient diet indicates that during starvation cardiac mRNA does not accumulate in the cell sap, but gets rapidly degraded. In the refeeding period, mRNA is transported from the nucleus to the cytoplasm and engages in polyribosome formation. The specific mRNA species coding for the major myofibrillar cardiac proteins are affected to a similar extent by these changes during starvation/protein-deprivation and refeeding. PMID- 2580513 TI - Effect of the calcium entry blocker, flunarizine, on ruthenium red uptake by endothelial cells following acute electrical stimulation of rabbit carotid arteries. AB - Local transmural electrical stimulation with DC of a carotid artery by means of implanted electrodes causes subendothelial fibromuscular proliferates or atheroma (if the animal receives a cholesterol-containing diet) beneath the anode. The endothelial lining is maintained when weak current is used for stimulation. The model permits studies of permeability of the endothelium in all stages of the plaque development. Ruthenium red as a marker for the glycocalyx is transiently taken up into the cytoplasm of the endothelial cells beneath the anode immediately after a 30 or 60 min lasting stimulation period. When staining the endothelium later than two hours after the end of an acute stimulation period, the ruthenium red staining is again normal. This indicates that the increased permeability to large molecules is reversible. Injection of the calcium entry blocker Flunarizine inhibited the cytoplasmic uptake of ruthenium red, showing that an increased entry of calcium into the endothelial cells may contribute to the disturbance in the permeability of large molecules into the endothelium. PMID- 2580514 TI - [Surgical treatment of osteochondrosis dissecans of the knee joint]. PMID- 2580512 TI - Adenosine-induced increase in myocardial adenine nucleotides without adenosine induced systemic hypotension. AB - In anaesthetized rabbits, the i.v. application of 1% adenosine (Ado) for 3 hours at a rate of 4 ml X h-1 X kg-1 body weight increased the myocardial tissue levels of adenine nucleotides (AN) above the normal values by 39%. This increase in ATP and the sum of AN is a metabolic effect of the continuous and high supply of Ado and does not result from the Ado-induced systemic hypotension: Neither a comparable hypotension and reduction of circulatory work induced by phentolamine nor a massive volume loading caused changes in the AN. The compensation of the Ado-induced hypotension by a simultaneous i.v. application of caffeine or xylometazoline did not interfere with the accumulation of AN. The increase in AN was less pronounced, if norepinephrine was infused to maintain normotension. The increase in AN occurred in left and right ventricular myocardium to a similar extent, although the pressure-volume-work of the left ventricle decreased, and that of the right ventricle increased during Ado-application. PMID- 2580515 TI - [Nucleoid sedimentation--a method for determination of DNA damage and DNA repair as exemplified by rat lymphocytes affected by physical and chemical agents in vitro]. PMID- 2580517 TI - The coiled-coil molecules of intermediate filaments consist of two parallel chains in exact axial register. AB - Amino acid sequence studies of helical particles derived from proteolytic digests of mouse epidermal keratin intermediate filaments (IF) have shown that their coiled-coil molecules are heterodimers of Type I and Type II keratins, with a parallel arrangement of the two chains. From a reappraisal of published chemical cross-linking data, it is concluded that the coiled-coil molecules in all IF consist of pairs of parallel chains in precise axial register. PMID- 2580516 TI - Vitamin A and bone formation. Effect of an excess of retinol on bone collagen synthesis in vitro. AB - The influence of an excess of retinol on bone formation was studied by using cultures of embryonic-chick calvaria. Retinol decreased collagen synthesis in a dose-dependent manner, non-collagenous protein synthesis being relatively unaffected. Collagen synthesis was significantly inhibited after 24 h of culture with retinol and was progressively decreased, compared with control cultures containing no retinol, as the period of culture was increased. The effect of retinol on collagen synthesis could be reversed by incubation of calvaria for further periods in retinol-free medium. Incorporation of [3H]thymidine and [3H]uridine into DNA and RNA respectively was not altered by culturing calvaria with retinol for 22 h. These latter findings, and the selectivity for collagen synthesis, all suggested that the effect observed was not a cell-toxicity phenomenon. The effect of retinol on collagen synthesis by chick calvarial osteoblasts was probably direct and not mediated by osteoclasts, since a negligible number of the latter cells is present in chick calvaria. In cultures of neonatal murine calvaria, which contain many osteoclasts, retinol similarly inhibited synthesis of collagen, but not of non-collagenous protein; the concentrations of retinol necessary to produce the response were similar to those required to stimulate bone resorption in vitro. PMID- 2580519 TI - Effects of diamide and iodoacetamide on the expression of the glycoprotein IIb/IIIa complex on blood platelets. AB - We have examined the effects of two agents that alter platelet thiol-disulphide status on platelet aggregation and on the ability of platelets to bind a monoclonal antibody (M148) that is directed toward an epitope on the glycoprotein IIb/IIIa complex. The immediate effect of both diamide and iodoacetamide is to enhance aggregation but after further incubation diamide, but not iodoacetamide, inhibits platelet aggregation. Incubation of platelets with diamide, but not iodoacetamide, is accompanied by a marked increase in the amount of M148 that binds to platelets. This is presumably a reflection of an altered distribution of glycoproteins on the platelet surface. It is known that diamide, but not iodoacetamide, leads to polymerisation of cytoskeletal proteins in platelets. Thus evidence is provided that agents that interact with the cytoskeleton inhibit platelet behaviour via an effect on surface glycoproteins. PMID- 2580518 TI - Immunological identity of a 60 kd oncofetal protein induced in rats by chemical carcinogens and released by transformed cells. AB - A 60,000 dalton (60 kd) oncofetal protein was previously shown to be produced by tumors in tumor-bearing rats and by target tissues within 3 weeks of carcinogen treatment. The factor is released to and accumulates in the blood in vivo and in the conditioned medium of cultured transformed cells in vitro. A polyclonal antibody produced against the 60 kd factor purified from the plasma of a rat carrying the N-2-fluorenylphthalamic acid-induced transplantable Hepatoma 7777, was tested against the 60 kd factor from various sources. Based on the results of immunoprecipitation of biochemical activity associated with the 60 kd factor, it was determined that these anti-60 kd antibodies cross-reacted with the factor released by a dimethylbenzanthracene-induced rat mammary carcinoma, with the factor in rat tumor cytosol and with rat spontaneous lymphoma cells, but not with a 60 kd factor isolated from pooled cancer patient plasma. Furthermore, these antibodies cross-reacted with the 60 kd factor induced within 21 days of treatment of the rats with a range of carcinogens from 8 chemical structural groups. The anti-60 kd factor antibodies did not cross-react with a 35 kd factor having similar biochemical activity found in normal adult cells. PMID- 2580520 TI - Ruthenium red and caffeine affect the Ca2+-ATPase of the sarcoplasmic reticulum. AB - Effects of ruthenium red and caffeine (a Ca2+ release blocker and an inducer, respectively) on Ca2+ uptake by sarcoplasmic reticulum (SR) vesicles and formation of the phosphorylated intermediate (EP) of the Ca2+-ATPase were studied using fast-kinetic techniques. Ruthenium red increased the rate and the maximum level of EP formation, while caffeine decreased both. Similarly, ruthenium red accelerated rapid Ca2+ uptake, while caffeine inhibited it. These drugs affected EP formation also with detergent solubilized Ca2+-ATPase. The concentrations required for half maximal effects on these functions (0.2 microM ruthenium red, 1.0 mM caffeine) are about the same as those for altering Ca2+ release. These results indicate that these reagents affect both the Ca2+-pump as well as the Ca2+ release mechanism, suggesting that the Ca2+-pump and Ca2+ release have some mechanisms in common. PMID- 2580521 TI - Exposure of DNA to methyl mercury results in an increase in the rate of its transcription by RNA polymerase II. AB - Double-stranded DNA which was exposed to methyl mercury at concentrations of 1 mM and above, and purified by ethanol precipitation and dialysis, was transcribed at a higher rate by RNA polymerase II than was control DNA. The rate of transcription of single-stranded DNA was not affected by similar exposure to methyl mercury. The higher rate of transcription of methyl mercury-treated double stranded DNA appears to result from a decreased Km of the enzyme for this DNA. This does not appear to result from extensive denaturation, nor from formation of a large number of single-stranded breaks in the DNA. PMID- 2580522 TI - Inhibition of RNA nucleo-cytoplasmic translocation by anti-nucleus antibody. AB - Anti-nucleus antibody was raised by immunizing rabbits with rat liver nuclei, and purified by affinity-column chromatography. When purified anti-nucleus IgG molecules were introduced into FL cells by the erythrocyte-ghost fusion method with HVJ (Sendai virus), release of RNA from the nucleus into the cytoplasm was inhibited in the presence of alpha-amanitin, but nuclear accumulation of 125I labeled non-histone chromosomal protein from the cytoplasm was not inhibited. These findings suggest that the nucleo-cytoplasmic transport mechanisms of RNA and nuclear proteins are different. The molecular weight of the antigen of this antibody was determined to be about 55K by the immunoblotting technique. PMID- 2580523 TI - Selenium prevents the growth stimulatory effects of cadmium on human prostatic epithelium. AB - Cadmium has been implicated in the increase in prostate cancer incidence in men exposed to high levels. A decrease in zinc and a concomitant increase in cadmium levels in the human prostate has been shown. The role and mechanism of cadmium action in prostate carcinogenesis is not clear. Selenium, on the other hand, has been shown to inhibit carcinogenesis in several animal systems. Results show that cadmium stimulates the growth of human prostatic epithelium in vitro, between 10( 9) M and 10(-7) M concentrations. Selenium, at concentrations between 10(-12) M and 10(-7) M shows no growth stimulatory or inhibitory effects on these cells. However, when present at 10(-8) M level, selenium inhibits the growth stimulation induced by cadmium. These results suggest that selenium may be useful in counteracting the effects of cadmium in the human prostate and offer possibilities for investigations on the protective effects of selenium in cadmium related carcinogenesis in man. PMID- 2580524 TI - Phosphorylation of glycophorin A in membranes of intact human erythrocytes. AB - The qualitative and quantitative contribution of glycophorin A phosphorylation to the general and specific pattern of membrane protein phosphorylation in intact erythrocytes pre-incubated with 32Pi was examined. Intense 32P-labeled bands at 88,000 and 38,000 Mr were identified as phosphorylated glycophorin A dimer and monomer respectively on the basis of several criteria. Quantitatively, phosphorylated glycophorin A dimer accounted for about 70% of 32P in the band 3 region. This value is at least three times that previously reported. The results of ancillary experiments involving selective extraction of ghosts in acidified chloroform/methanol solvents and electrophoresis in the presence of detergents make it unlikely that the 32P associated with glycophorin A was due to bound polyphosphoinositides. PMID- 2580525 TI - Characterization of monoclonal antibodies to the IGF-I receptor that inhibit IGF I binding to human cells. AB - A mouse monoclonal antibody directed against the human placental IGF-I receptor is shown to completely inhibit IGF-I binding to both human placental membranes and circulating human mononuclear leukocytes. Insulin binding is unaffected. Studies with 125I-labelled anti-receptor antibody indicate that the antibody reacts with an epitope distinct from the IGF-I binding site. These antibodies will be powerful probes of IGF-I binding and action in human cells. PMID- 2580526 TI - Stimulation and inhibition of secretion by phorbol myristate acetate in different cell types. AB - In washed human platelets and in HL60 granulocytes phorbol myristate acetate (PMA, 1-2000nM) synergised with threshold concentrations of secretogogues to induce a sustained maximum secretory response. Likewise, superoxide production from HL60 cells maintained a maximal response at PMA concentrations between 30 300nM. At concentrations up to 10nM PMA also augmented calcium ionophore, A23187, stimulated histamine release from rat peritoneal mast cells. However, in the mast cell PMA concentrations above 10nM reduced maximum histamine release in a dose dependent manner. PMID- 2580527 TI - Cation-dependent substance P activation of the enzyme guanylate cyclase. AB - Substance P enhanced guanylate cyclase (E.C.4.6.1.2) two- to fourfold in pancreas, small intestine, cerebellum, liver, kidney, and lung. Dose response relationship revealed that substance P caused a maximal augmentation of guanylate cyclase activity at concentration of 1 micromolar. Increasing substance P's concentration to the millimolar range caused no further increase in activity. There was an absolute cation requirement for substance P's enhancement of guanylate cyclase activity. Substance P could increase guanylate cyclase activity with either calcium or manganese in the incubation medium but more augmentation was observed with manganese. The data in this investigation suggest that guanylate cyclase may play a role in the mechanism of action of substance P. PMID- 2580528 TI - Study of antigenic epitopes recognized by monoclonal antibodies to recombinant interferon-gamma. AB - Seven hybridomas (BG 1-7) which secreted monoclonal antibodies against recombinant interferon-gamma were produced. The ascites fluids containing four of the seven monoclonal antibodies (BG 1-4) neutralized the antiviral activity of both natural and recombinant interferon-gamma. Competition between labeled and unlabeled monoclonal antibodies for interferon-gamma in a solid phase immunoassay showed that BG 1 was competed by both BG 3 and BG 4 but not by BG 2; BG 2 was competed by BG 3 but not by BG 1 nor by BG 4. These results suggest that human interferon-gamma has at least two antigenic epitopes; one of the epitopes reacted with BG 1 & BG 4 while the other reacted with BG 2; BG 3 either binds to a region overlapping with the other two epitopes or reacts with both epitopes. The antigenic epitopes recognized by these four neutralizing monoclonal antibodies are likely at or closely related to the active sites of interferon-gamma. PMID- 2580529 TI - Potentiation of thermal injury in mouse cells by interferon. AB - Mouse cells, when exposed to high temperature (43 degrees), shut off overall protein synthesis and continue to synthesize "heat shock proteins". Such heat shocked cells, upon reincubation at 37 degrees C, recover and proliferate. However, when mouse cells are pretreated with mouse interferon (IFN) and then exposed to 43 degrees, more than 99% of the cell population fail to recover. Synthesis of the major heat shock protein is unaffected in cells treated with IFN. Experiments designed to assess the role of intracellular glutathione (GSH) during cells' recovery from hyperthermia indicated that there is an irreversible depletion of glutathione when IFN treated cells are heat shocked. Neither depletion of GSH, nor potentiation of thermal injury was observed in a IFN resistant line of mouse cells. PMID- 2580530 TI - Substance K and substance P as possible endogenous substrates of angiotensin converting enzyme in the brain. AB - In the brain angiotensin converting enzyme is highly localized to a striatonigral pathway, which contains no endogenous angiotensin. Substance P, also localized to a striatonigral pathway, is degraded by ACE via two different pathways. The lung and striatal isozymes of angiotensin converting enzyme exhibit differential cleavage of substance P, with lung preferring an initial tripeptide cleavage, and striatum an initial dipeptide cleavage. Substance K is degraded by the striatal isozyme but is not cleaved by the lung isozyme. Substance P 5-11 is not cleaved by either form of angiotensin converting enzyme. PMID- 2580531 TI - Monoclonal antibody-defined circulating human tumor-associated antigen with epitope shared by cytokeratins. AB - Sera of human colonic carcinoma xenografted rnu/nu rats were used to immunize rnu/+rats in order to obtain an immune response against circulating human tumor associated components. After fusion of rat spleen cells with mouse myeloma cells monoclonal antibody MAB 108 could be established which reacted with two 40 and 45 kD cytokeratins as well as with vimentin, with a soluble 37 kD protein apparently derived from the 45 kD protein and with a 37 kD protein released by tumor cells. The MAB 108-specific epitope was also detected in tissue polypeptide antigen (TPA), a human tumor-associated antigen originally described by Bjorklund et al. (22). PMID- 2580532 TI - Role of carbohydrate in glycoprotein secretion by human hepatoma cells. AB - We have previously shown that export of nine proteins by human hepatoma cells falls into three discrete kinetic classes with intracellular retention half-times of approximately 35 min, 77 min and 115 min. To determine if carbohydrate on secretory glycoproteins determines the secretory class we have measured the kinetics of export of the nine proteins after tunicamycin-treatment of cultures. We found no apparent correlation between the kinetic class of a secretory protein and sensitivity of secretion to tunicamycin-treatment. For example, three glycoproteins are exported with rapid kinetics and secretion of only one, alpha 1 protease inhibitor, is inhibited by tunicamycin treatment. In addition, three glycoproteins are secreted with intermediate kinetics and tunicamycin-treatment inhibits the secretion of two of these proteins, alpha 2-macroglobulin and ceruloplasmin but not the third, plasminogen. PMID- 2580533 TI - Evidence for naturally occurring hyaluronic acid binding protein in rat liver. AB - Hyaluronic acid binding protein (HBP) was purified homogeneously from normal adult rat liver by hyaluronate-sepharose affinity chromatography. The molecular weight of this protein as determined by gel filtration was found to be 64,000 daltons. This protein HBP appeared as a single band in non-dissociating gel electrophoresis and has a subunit of molecular weight approximately 12,000 as determined by SDS-gel electrophoresis. PMID- 2580534 TI - Modulation of rat pancreatic muscarinic cholinergic receptors by caerulein. AB - To evaluate the modulation of pancreatic muscarinic receptors in two states of pancreatic growth, hypertrophy and hyperplasia, caerulein, a cholecystokinin analog, (1 microgram/kg) was administered thrice daily for 2 and 4 days to adult rats. After 2 days of treatment, pancreatic hypertrophy was well established as evidenced by increases in pancreatic weight, cellular mass and protein content. Using an increase in DNA content as an index of hyperplasia, we demonstrated that pancreatic hyperplasia occurred only after 4 days of caerulein treatment. Caerulein increased the concentration of muscarinic receptors per DNA in pancreatic homogenate by 57% over control value after 2 days of treatment without modification of the receptor affinity for the ligand QNB. This increase involved mainly receptors in the low affinity state for carbamylcholine and their concentration returned to control levels after 4 days of treatment. The functional capacity of the acini was significantly increased after 2 days of caerulein as amylase release (U/mg DNA) was significantly increased but the sensitivity of these acini to carbamylcholine was significantly decreased. After 4 days of caerulein, the functional capacity has returned towards control values but the sensitivity to carbamylcholine remained decreased. The increase in muscarinic receptor concentration could be ascribed to a general increase in cellular proteins, as part of the hypertrophic effect of caerulein. This specific effect would also explain the increased functional secretory capacity of the caerulein-treated acini but the decreased sensitivity to carbamylcholine probably resulted in changes at a postreceptor loci since the affinities of the muscarinic receptors for carbamylcholine remained unaffected. PMID- 2580535 TI - Regulation of angiogenesis: a new function of heparin. PMID- 2580536 TI - [Synthesis of moraprenylpyrophosphate disaccharides--precursors of the biosynthesis of Salmonella O-antigenic polysaccharides of C2 and C3 serotypes]. AB - Disaccharides Man(alpha 1-3)Gal and Man(beta 1-3)Gal and their acetates have been synthesized, from which alpha-glycosyl phosphates were obtained by the MacDonald reaction. These compounds were converted into corresponding moraprenylpyrophasphate disaccharides by treating with moraprenylphosphoimidazolidate. PMID- 2580537 TI - Spontaneous in vitro production of anti-DNA and anti-RNA by systemic lupus erythematosus and normal peripheral blood mononuclear cells. AB - The spontaneous in vitro production of anti-DNA and anti-RNA by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE) and from normal subjects was evaluated employing sensitive solid-phase assays that are specific for these antibodies. PBMC from SLE patients produced more IgG anti-DNA and anti-RNA than did normal PBMC (P less than 0.01). In vitro production of IgG anti-DNA appeared to correlate with serum DNA bindings (r = 0.72, P less than 0.005). Similar amounts of IgM anti-DNA and anti-RNA were produced by both SLE and normal PBMC. However, IgM anti-DNA antibodies always appeared to be directed against determinants on denatured DNA. Only PBMC from SLE patients produced IgG antibodies to native DNA. PMID- 2580538 TI - Raynaud's phenomenon of a single digit following local intradermal bleomycin sulfate injection. PMID- 2580539 TI - Enhanced breakdown of bovine articular cartilage proteoglycans by conditioned synovial medium in vitro. The effect of glycosaminoglycan polysulfate. AB - The effect of glycosaminoglycan polysulfate (GAGPS, Arteparon) upon the breakdown of calf articular cartilage proteoglycans has been studied in vitro. GAGPS had no significant effect upon this breakdown when cartilage was cultured alone but significantly reduced the breakdown enhanced by conditioned medium from organ cultures of calf synovial membrane. Culturing the synovial membrane in the presence of GAGPS did not alter the capacity of conditioned medium to degrade cartilage proteoglycans. PMID- 2580540 TI - 4-(Indolyl-3)-1-(benzimidazolonylalkyl)-piperidines, a novel group of potential antiallergy compounds. AB - A group of indolyl-benzimidazolone-piperidines is described and the structure activity with reference to the passive cutaneous anaphylaxis (PCA) in rats is discussed. Compound 7b, 4-(indolyl-3)-1-(benzimidazolonyl-propyl)-piperidine, which has the highest potency in this test, was studied in more detail with regard to antihistaminic and secretory cell stabilization properties. PMID- 2580542 TI - Acute monosymptomatic aseptic meningitis caused by Toxoplasma gondii. AB - Acute monosymptomatic aseptic meningitis was observed in a 4 year old male patient. Toxoplasma gondii tachyzoites were detected in Giemsa-stained smears prepared from the CSF. Inoculation of mice gave the same result. The patient was cured after the application of pyrimethamine and sulpha drugs. On basis of the smears, the serological results and data in the literature, a direct infection through the nasal cavity has been assumed. PMID- 2580541 TI - The use of a diuretic agent as a probe to investigate site and mechanism of ion transport processes. AB - Several features emerge from consideration of a furosemide-sensitive cotransport mechanism in the various tissues surveyed. First discovered in epithelia, above all in the kidney because of its potent diuretic effect, furosemide inhibits a cotransport mechanism that tightly couples the movement of sodium, chloride and potassium. Its mode of operation is electrically neutral and in all tissues so far examined, the cotransport-mediated ion movement is driven by the electrochemical potential of the cotransported ion-species. The energy for this ion movement derives ultimately from the Na-K pump that establishes the Na gradient that drives the coupled ion movement. This type of carrier-mediated and ion-specific solute movement expands the traditional "pump-leak" model of cellular ion transport by providing dissipative "leak" pathways in addition to the well-established ion channels that allow solute movement by electrodiffusion. An important feature of the cotransport mechanism is its important role in both reabsorptive and secretory epithelial transport operations. This variability can be adequately explained by the location of the cotransport mechanism in either the apical or basolateral cell membrane of such epithelia as the renal tubule, the intestinal mucosa, the rectal gland or the trachea. In addition, the furosemide-sensitive transporter has also been shown to play a significant role in cell volume regulation, both in epithelia and in non-epithelia cells, and it appears to participate in the regulation of the cell chloride concentrations in excitable tissues. PMID- 2580543 TI - Use of flupirtine maleate as an analgesic in patients with liver disease. PMID- 2580544 TI - Natural killer cell activity in tuberculosis. AB - Natural killer (NK) cell activity was studied in 27 patients with active tuberculosis and 27 healthy controls matched for age, sex, ethnic origin and diet. Spontaneous and interferon (IFN)-augmented NK cytotoxicity against K562 target cells were measured, using a 4-hour 51Cr-release assay. There were no differences between the patients and their matched controls in mean spontaneous and IFN-augmented cytotoxicity before and during antituberculosis chemotherapy. However, one malnourished alcoholic patient with extensive non-reactive multibacillary disease had depressed NK cell activity which was not significantly enhanced by in vitro pretreatment with leucocyte IFN. We conclude that the NK system is not of prime importance in host defence against human tuberculosis, although advanced disease may be associated with deficient NK activity, as part of generalized anergy. PMID- 2580545 TI - Bronchoscopic implantation of radioactive gold grains into endobronchial carcinomas. AB - We report the results of palliative treatment of non-resectable obstructing endobronchial carcinoma by bronchoscopic implantation of radioactive gold grains in 18 patients. Dyspnoea and collapse of a lobe or a lung were successfully treated in 13 cases where tumour was locally confined to a main or lobar bronchus. The response was maintained until death in nine of these patients but obstruction recurred in four longer surviving patients with tumours of main bronchus after a mean interval of 6 months. Treatment was less successful in five patients with tumour extending onto the trachea. The low penetration of interstitial radiation offers the advantage that normal lung and other tissues are not damaged, so that the procedure can be used in patients previously submitted to external radiotherapy. PMID- 2580546 TI - Clinical chemical responses to experimental airborne legionellosis in the guinea pig. AB - Legionella pneumophila infection of guinea-pigs by the aerosol route with either of two strains, one (serogroup I) giving an acute the other (serogroup 3) giving a protracted illness, induced a pyrexia and similar pneumonic lesions. With both strains there was a bacteraemia with early decreases in serum iron and zinc and increases in serum copper concentrations. Marked changes in other serum components were evident only in those animals which had protracted illness (serogroup 3-infected animals). These included transient increases in aminotransferase, creatine kinase and sorbitol dehydrogenase activities and triglyceride levels, together with gradual decreases in alkaline phosphatase and leucine aminopeptidase activities. Serum lysozyme activity and acute-phase protein synthesis increased, as did the ratio of phenylalanine to tyrosine. The findings confirm the relevance of the aerosol-infected guinea-pig model for the investigation of the disease processes and evaluation of therapeutic measures for use in man. PMID- 2580548 TI - The destabilization of factor VIII by a vitamin K dependent protein. AB - Since a vitamin K dependent protein, protein C, can inactivate factor VIII, a study was undertaken to determine if the level and stability of factor VIII in plasma are influenced by such a protein. Factor VIII lability was determined by incubating citrated plasma, diluted 1:10 and 1:20 in pH 7 X 2 imidizole buffer, for 6 h at 37 degrees C. Normal plasma had a mean factor VIII of 98 +/- 61 U/100 ml. The amount of factor VIII remaining after 6 h of incubation was 68 +/- 14% of the original factor VIII level. In warfarinized patients, factor VIII (218 +/- 65 U/100 ml) and VWF:AGN (331 +/- 102 U/100 ml) were elevated (P less than 0.001). Following incubation, their residual activity was 103 +/- 20% of the original factor VIII level. In samples taken after warfarin was discontinued, normal factor VIII lability returned, while plasma levels of factor VIII and VWF:AGN remained elevated. Similarly, in the plasma of a vitamin K deficient patient, increased factor VIII stability was also evident; lability was restored following vitamin K replacement. We conclude that factor VIII stability is determined in part by a vitamin K dependent protein. In clinical states in which this protein is functionally absent, factor VIII is elevated and more stable. PMID- 2580547 TI - An immunoradiometric assay for human factor VIII/von Willebrand factor (VIII:vWF) using a monoclonal antibody that defines a functional epitope. AB - A murine monoclonal antibody has been produced (RFF-VIII:R/2) that binds specifically to human factor VIII-related antigen (VIII:RAg) in plasma and in vascular endothelial cells but has no reactivity with factor VIII procoagulant antigen (VIII:cAg). This antibody is a potent inhibitor of von Willebrand factor activity (VIII:vWF) in that it can totally neutralize ristocetin-induced aggregation of platelet rich plasma and inhibit platelet adhesion at high flow rates. RFF-VIII:R/2 can be used in a one-stage, fluid phase immunoradiometric assay that can detect VIII:RAg at concentrations of 0.001 u/ml. This method has been used to analyse plasma from patients with von Willebrand's disease (vWD). Results obtained in these patients showed a high degree of correlation between the monoclonally-defined epitope and VIII:vWF levels measured by ristocetin induced aggregation of washed platelets. This correlation was maintained in those patients with the 'variant' types of vWD who exhibit highly disparate VIII:vWF and VIII:RAg levels when the latter is determined using polyclonal antisera. It appears that this monoclonal antibody recognizes a site on the VIII:RAg molecule which is associated with its interaction with the platelet membrane. Immunoradiometric assays using RFF-VIII:R/2 offer a simplified, reproducible means of detecting functionally-active VIII:RAg as an alternative or supplement to techniques involving platelet interactions. PMID- 2580549 TI - Computerized histories facilitate patient care in a termination of pregnancy clinic: the use of a small computer to obtain and reproduce patient information. AB - An inexpensive microcomputer has been programmed to obtain histories from patients attending a pregnancy termination clinic. The system is nurse interactive; yes/no and multiple-choice questions are answered on the visual display unit by a light pen. Proper nouns and discursive text are typed at the computer keyboard. A neatly formatted summary of the history is then provided by an interfaced printer. The history follows a branching pattern; of the 370 questions included in the program, only 68 are answered in the course of an average history. The program contains numerous error traps and the user may request explanations of questions which are not immediately understood. The system was designed to ensure that no factors of anaesthetic or medical importance would be overlooked in the busy out-patient clinic. The computer provides a much more complete history with an average of 42 more items of information than the pre-existing manual system. This system is demanding of nursing time and possible conversion to a patient-interactive system is discussed. A confidential questionnaire revealed a high degree of consumer acceptance. PMID- 2580550 TI - alpha-Fetoprotein elevation and proteinuric pre-eclampsia. AB - In a retrospective study of pregnancy complicated by unexplained elevation of maternal serum alpha-fetoprotein (AFP), 60 patients were compared with 120 control subjects. Proteinuric pre-eclampsia occurred in 13% of the study patients compared with 1% of the control subjects. Primiparity, previous mid-trimester abortion and recurrent abortions were also significantly more common in the study group. It is proposed that an abnormality of the placenta predisposes to complications and that this abnormality is expressed early in pregnancy when the AFP level is first measured. This group of women is at high risk of adverse pregnancy outcome and requires careful monitoring. PMID- 2580551 TI - Hormonal profiles in the follicular phase, luteal phase and first trimester of pregnancies arising from in-vitro fertilization. AB - The hormonal profiles for oestradiol-17 beta, progesterone, prolactin and beta human chorionic gonadotrophin (beta-hCG) are documented for the first 24 pregnancies arising from in-vitro fertilization during a collaborative project between the University of Western Australia and PIVET Laboratory. All patients had ovarian follicle stimulation with clomiphene citrate, sometimes combined with human menopausal gonadotrophin and all had oocyte recovery undertaken 36 h after injection of 5000 i.u. hCG. The follicular phase profile indicated that patients were admitted for the hCG injection when oestradiol-17 beta levels were around 1500 pmol/l per follicle with a dimension of greater than or equal to 1.6 cm on ultrasound. Luteal phase data indicated that oestradiol-17 beta and progesterone levels were two to three times higher than that expected during spontaneous conception cycles and those pregnancies which subsequently aborted had significantly lower levels in the late luteal phase. During pregnancy elevated oestradiol-17 beta and progesterone levels were maintained through the early weeks during organogenesis while the beta-hCG profile was similar to that reported for spontaneous pregnancies arising without ovarian stimulation. Six women aborted and the other 18 pregnancies have generated 22 infants. PMID- 2580552 TI - Are vaginal fluid concentrations of prolactin, alpha-fetoprotein and human placental lactogen useful for diagnosing ruptured membranes? PMID- 2580553 TI - Inhibition of Na+/Ca2+ exchange in pituitary plasma membrane vesicles by analogues of amiloride. AB - Amiloride is a weak inhibitor of Na+/Ca2+ exchange in isolated plasma membrane vesicles prepared from GH3 rat anterior pituitary cells. However, substitution on either a terminal guanidino nitrogen atom or the 5-amino nitrogen atom can increase inhibitory potency ca. 100-fold (I50 approximately 10 microM). A structure-activity study indicates that defined structural modifications of guanidino substituents are associated with increases in inhibitory activity. In contrast, analogues bearing 5-amino substituents generally increase in potency with increasing hydrophobicity of the substitution. Specificity in action of either class is indicated by several criteria. These inhibitors do not disrupt the osmotic integrity of the membrane, nor do they significantly interfere with plasmalemmal Ca2+-ATPase-driven Ca2+ uptake, Na+,K+-ATPase enzymatic activity, or the function of Ca2+ or K+ channels. Inhibition is freely reversible, further indicating a lack of nonspecific membrane effects. The mechanism by which each inhibitor class blocks exchange was found to be identical. Protonation of the guanidino moiety (i.e., cationic charge) is essential for activity. Analysis of transport inhibition as a function of Ca2+ concentration indicates noncompetitive kinetics. However, inhibition was reversed by elevating intravesicular Na+, indicating a competitive interaction with this ion. These results suggest that the inhibitors function as Na+ analogues, interact at a Na+ binding site on the carrier (presumably the site at which the third Na+ binds), and reversibly tie up the transporter in an inactive complex. In addition to blocking pituitary exchange, these analogues are effective inhibitors of the bovine brain and porcine cardiac transport systems. PMID- 2580554 TI - Tissue antigens in large-bowel carcinoma. PMID- 2580555 TI - Hypothesis. Cytochrome c oxidase as a proton pump. A transition-state mechanism. PMID- 2580556 TI - Evidence against involvement of the human erythrocyte plasma membrane Ca2+-ATPase in Ca2+-dependent K+ transport. AB - Two tests were performed to assess the relationship between the Ca2+-activated K+ channel and the Ca2+-pumping ATPase in human erythrocytes. Antibodies against the purified ATPase inhibited the ATPase in resealed erythrocytes, but had no effect on the K+ channel (as assessed by Rb+ efflux). Reconstituted liposomes containing the purified active Ca2+-pumping ATPase showed no Ca2+-activated Rb+ influx. Both of these results suggest that some molecule other than the Ca2+-ATPase is responsible for the K+ channel. PMID- 2580557 TI - Apurinic/apyrimidinic-specific endonuclease activities from Dictyostelium discoideum. AB - Two apurinic/apyrimidinic- (AP-) specific endonuclease activities have been isolated from the cells of Dictyostelium discoideum by fractionation on DEAE cellulose, CM-cellulose and Sephadex G-75. These activities, designated A and B, have apparent molecular weights of 49000 and 40000, respectively. Although their precise reaction optima differ somewhat, both A and B quantitatively nick AP DNA best at pH 8.0-8.5 in low salt (less than 100 mM NaCl); both require Mg2+. These activities are apparently specific only for AP sites in DNA. The low activities observed on heavily ultraviolet-irradiated DNA, gamma-irradiated DNA and osmium tetroxide-treated DNA are consistent with the small numbers of secondary AP sites expected in these DNAs. Both A and B produce single-strand nicks in AP DNA that result in termini that serve as good primers for Escherichia coli polymerase I. Hence, A and B appear to be Class II AP endonucleases which yield 3'-OH termini at nicks on the 5' side of baseless sugars. It is unclear whether A and B are independently coded proteins, different post-translational modifications of the same gene product, or whether one is an artifact arising from the isolation. Many of the properties of these D. discoideum AP endonuclease activities are similar to those of the predominant AP endonucleases observed in bacterial, plant and animal cells. They will be of use in the characterization of excision repair in this organism. PMID- 2580559 TI - RNA synthesis in male pronuclei of the sea urchin. AB - Transcription in male pronuclei of fertilized sea urchin eggs was measured by comparison of [3H]uridine incorporation into RNA in polyspermic, monospermic and activated eggs under conditions where uptake of the isotope and conversion to UTP were equivalent. RNA accumulation from male pronuclei begins by S phase of the first cell cycle. Initiation of this RNA synthesis does not require DNA synthesis. A major fraction of the newly synthesized transcripts are mRNAs coding for early embryo (alpha-) histones. In addition, several other unidentified transcripts are detected by gel electrophoresis. The pattern of RNA transcription remains constant for at least 4 h post-fertilization. These results demonstrate that specific transcription of male pronuclear sequences is activated in the first cell cycle following fertilization. PMID- 2580558 TI - Nucleotide sequence cleavages of manganese-bleomycin induced by reductant, hydrogen peroxide and ultraviolet light. Comparison with iron- and cobalt bleomycins. AB - The prominent DNA breakages of bleomycin-Mn complex system were induced by reductant, hydrogen peroxide and ultraviolet light, and these three induction systems gave remarkably similar nucleotide sequence cleavage modes. The preferred DNA cleavage sites at guanine-cytosine(5'----3') and guanine-thymine(5'----3') sequences were appreciably comparable to those of the corresponding bleomycin-Fe complex systems, but not identical. In contrast, the bleomycin-Co complex system significantly degraded isolated DNA only by irradiation of ultraviolet light. The present results provide valuable information on the role of transition metals on DNA cleavage reaction of bleomycin. PMID- 2580560 TI - Lymphocyte blastogenesis. Post-transcriptional controls of protein synthesis. AB - To better understand the regulation of macromolecular synthesis in the response of lymphocytes to a mitogen, we have used two-dimensional electrophoresis to search for specificity in the early increase seen in protein synthesis in human lymphocytes treated with phytohemagglutinin and examined the role of new RNA synthesis in this response. Our results confirm a major increase in overall protein synthesis after 4 h of phytohemagglutinin treatment. A further disproportionate increase in the synthetic rates of certain polypeptides was observed using two-dimensional polyacrylamide gel electrophoresis. While actinomycin-D reduced protein synthesis to a level below that of untreated cells, phytohemagglutinin nonetheless enhanced total protein synthesis even in the presence of actinomycin. Some, but not all, of the disproportionate increases in synthesis seen for certain polypeptides are blocked by actinomycin. These results imply the existence of multiple mechanisms controlling protein synthesis early in the course of lymphocyte stimulation. At least some of these do not require new RNA synthesis and thus operate at a post-transcriptional level. PMID- 2580561 TI - Human acetylcholinesterase. Immunochemical studies with monoclonal antibodies. AB - Monoclonal antibodies were used to investigate the immunochemistry of human erythrocyte acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7). A series of experiments on the sedimentation velocity and Stokes radius of acetylcholinesterase and its immune complexes indicated that each antibody recognized a single high-affinity binding site (epitope) on the monomeric enzyme. Further analysis suggested that the antibody-binding sites were replicated on multimeric enzyme forms but were subject to steric hindrance between nearby IgG molecules or adjacent enzyme subunits. The cellular localization of the epitopes was studied by measuring the binding of monoclonal antibodies to the cholinesterase of intact erythrocytes. The results implied that most of the epitopes are exposed to the external media. However, one antibody failed to bind to intact cells, despite a relatively high affinity for detergent-solubilized antigen, possibly because its epitope is buried in the lipid bilayer. PMID- 2580562 TI - Difference in dose-response curves for glucose-induced insulin and somatostatin release in rat pancreas. AB - We studied the glucose dependence of insulin and somatostatin release from rat pancreata, which were perfused in vitro in the presence of 3-isobutyl-1 methylxanthine (IBMX; 0.5 mM). Half-maximal insulin release occurred at approx. 12 mM glucose, and half-maximal somatostatin release at approx. 7 mM glucose. PMID- 2580563 TI - [Binding of small molecules with nucleic acids having tertiary structure]. AB - A model has been developed which allows description of the binding of antibiotics and dyes to a nucleic acid in which different regions are involved in the formation of a certain tertiary structure. Interactions between different segments of nucleic acid may contribute to the internal overall energy of the macromolecule. We consider the case when the tertiary structure and the internal energy of the macromolecule are altered upon binding of small molecules. These structural changes affect the shape of the binding isotherm of ligand to the nucleic acid. We obtain relations which permit to determine the dependence of the internal energy on the degree of binding of ligand to nucleic acid. PMID- 2580564 TI - [Effect of amphotericin B added to one side of a membrane]. AB - Amphotericin B which was added to the one side of a membrane in aqueous solutions with low pH 3.0 sharply increases the membrane conductance by the mechanism of channel forming. Long living ionic channels (20 sec) with large conductance dispersion (2-20 Ps) were found at the concentration 2 X 10(-8) M. Amphotericin B concentration which is necessary for obtaining single channels does not depend on cholesterol concentration in the membrane-forming solution in the range from 2 to 10 mg/ml. The effect of amphotericin B on the membrane depends on the phospholipid concentration in the membrane. The one-side selective permeability is the same as one under the symmetric action of the antibiotic. It is assumed that amphotericin B induced the membrane conductance by the mechanism of half pores formation. PMID- 2580566 TI - [Initiation of RNA synthesis in isolated rat liver nuclei]. AB - Isolated rat liver nuclei were incubated under conditions when RNA polymerase I or RNA polymerase II was preferentially active. It was shown that [gamma-32P] ATP and [gamma-32P] GTP were incorporated into phenol extractable, TCA-precipitable material. RNase, actinomycin D, heparin and, in the case of RNA-polymerase II, alpha-amanitine inhibited precursor incorporation. These data are interpreted as evidence in favour of the initiation of RNA synthesis in isolated rat liver nuclei. PMID- 2580565 TI - [The theory of regulation of the contraction force of the heart muscle]. AB - A model of rhythmoinotropic phenomena in the heart muscle is elaborated. Kinetics of calcium flowing in intracellular pools of cardiomyocytes is described by differential equations. Dimensionless values (portions) serve as equation coefficients. They determine calcium kinetics in the pools and finally its amount is liberated into the myoplasm during stimulation. Proceeding from physiological considerations for portions there are given laws connecting portion values with intervals between stimuli. S-pool introduced into the model is principally new, it permits quantitative description of the effects of postextrasystolic potentiation and paired stimulation. Introduction of S-pool into the model changes the commonly accepted concept of calcium recirculation in the pools, and apparently, makes it possible for the first time to model all the results obtained on isolated myocardium of warm-blooded animals. PMID- 2580567 TI - [Conditions of stability for the quaternary structure and antigenic activity of adenovirus hexon]. AB - The procedure of SDS-PAGE was modified by lowering the temperature of protein sample dissociation to allow the separation of denaturated adenoviral hexon chains and native hexon capsomers (trimers) in the same gel. By combining the modified SDS-PAGE with dot and blot radioimmunoassays, the range of stability of the simian adenovirus SA7 hexon quaternary structure and its antigenicity was studied against a number of physical and chemical agents known to dissociate and denaturate proteins. A perfect correlation was found between the hexon native quaternary structure (trimer) and its immunoreactivity with anti-hexon immunoglobulins. The pattern of hexon trimer stability to a wide spectrum of denaturants suggests that its subunits are held together, mainly by hydrophobic interactions, in such a way that the innersubunit contact regions make up the "hydrophobic core" of the hexon molecule. PMID- 2580568 TI - [Channel-forming action--a general property of venoms of spiders in the family Theridiidae (Aranei)]. AB - The study of venom action of 10 spider species of Theridiidae family has shown that they cause the formation of the cation selective channels on the bilayer lipid membranes. This action does not depend on the species sex and age and it is the important diagnostic characteristic of the family. The channel-forming effect is due to the presence of the peptide with molecular weight about 5000 daltons in venoms of Theridiidae spider family. PMID- 2580569 TI - Kinetic analysis of channel gating. Application to the cholinergic receptor channel and the chloride channel from Torpedo californica. AB - Identification of the minimum number of ways in which open and closed states communicate is a crucial step in defining the gating kinetics of multistate channels. We used certain correlation functions to extract information about the pathways connecting the open and closed states of the cation channel of the purified nicotinic acetylcholine receptor and of the chloride channel of Torpedo californica electroplax membranes. Single channel currents were recorded from planar lipid bilayers containing the membrane channel proteins under investigation. The correlation functions are conveniently computed from single channel current records and yield information on E, the minimum number of entry/exit states into the open or closed aggregates. E gives a lower limit on the numbers of transition pathways between open and closed states. For the acetylcholine receptor, the autocorrelation analysis shows that there are at least two entry/exit states through which the open and closed aggregates communicate. The chloride channel fluctuates between three conductance substates, here indentified as C, M, and H for closed, intermediate, and high conductance, respectively. Correlation analysis shows that E is greater than or equal to 2 for the M aggregate, indicating that there are at least two distinct entry/exit states in the M aggregate. In contrast, there is no evidence for the existence of more than one entry/exit state in the C or H aggregates. Thus, these correlation functions provide a simple and general strategy to extract information on channel gating kinetics. PMID- 2580570 TI - Voltage-dependent removal of sodium inactivation by N-bromoacetamide and pronase. AB - When perfused internally through crayfish giant axons, pronase removed sodium inactivation more than three times as fast at -100 mV as compared with -30 mV. N bromoacetamide, applied internally, removed sodium inactivation twice as fast at 100 mV as at -30 mV, and the relative rate of removal declined with membrane depolarization in proportion to steady-state sodium inactivation. We conclude that in the closed conformation the sodium inactivation gate is partially protected from destruction by N-bromoacetamide and pronase. PMID- 2580572 TI - Poly(DL-proline), a synthetic polypeptide behaving as an ion channel across bilayer membranes. AB - The synthesis and characterization of poly(DL-proline) are reported in relation with its predicted property of forming ion channels across membranes. The analysis of the conductance induced in synthetic bilayer membranes doped with poly(DL-proline) shows ionic permeoselectivity and the characteristic time course of fluctuations of ion channels, according to the similarity with the active structure of gramicidin A in membranes during the ion passage. An alternative mechanism of ion transport across bilayer membranes is also advanced. PMID- 2580571 TI - Conductance and selectivity properties of a substate of the rabbit sarcoplasmic reticulum channel. AB - In this paper I describe the occurrence and properties of a subconductance state of the cation-selective channel of the sarcoplasmic reticulum. The substate conductance is 60% of the major state conductance in every salt solution examined. When single channel conductance is plotted vs. ion concentration (for potassium or thallium salt solutions) the Michaelis-Menten constant is nearly the same for both conductance states, while the maximum conductance is reduced for the subconductance state. Both conductance states show anomalous conductance behavior in mixed potassium-thallium solutions that may be modeled in the same way. These results indicate that the ionic selectivity of the channel is the same for both open states. PMID- 2580573 TI - The carbohydrate specificities of the monoclonal antibodies 29.1, 455 and 3C1B12 to the epidermal growth factor receptor of A431 cells. AB - Sixteen hybridoma-derived antibodies to the epidermal growth factor receptor of A431 cells were studied with respect to their reactions with blood group-related carbohydrate structures. Twelve of these were assessed as recognizing carbohydrate determinants on the basis of their immunostaining of reference blood group substances on nitrocellulose paper. Three of these antibodies were further investigated by inhibition of binding assays with glycoproteins and structurally defined oligosaccharides or by haemagglutination of erythrocytes before and after treatment with endo-beta-galactosidase. Two of the antibodies, 29.1 and 455, were shown to have blood group A-related specificities which differed from one another and from those of monoclonal anti-A antibodies described previously. The third antibody, 3C1B12, which was shown to recognize a determinant based on alpha 1--- 3 fucosylated Type 2 chains on linear and branched backbone sequences, also differs from previously described monoclonal antibodies of 3-fucosyl-N acetyllactosamine type, such as anti-SSEA-1 (anti-mouse embryo) and several antibodies to human myeloid cells. While these antibodies are invaluable in providing structural information on the carbohydrate chains of the receptor glycoprotein and should help to elucidate their functions, their use as 'anti receptor' reagents in cell biology will be influenced by the knowledge that the determinants they recognize are shared by other glycoproteins and glycolipids of diverse cell types. PMID- 2580574 TI - Reconstitution of the complement channel into lipid vesicles and planar bilayers starting from the fluid phase complex. AB - Proteolysis of the fluid phase complement complex SC5b-9 transforms it into an amphiphilic molecule which resembles the membrane attack complex of complement and reconstitutes into lipid vesicles. Complement-containing vesicles prepared in this way can be made to fuse with planar lipid bilayers transferring their protein content to the host membrane. Massive conductance increases can thus be observed, which are due to the insertion of a large number of ionic channels into the membrane. Using low concentrations of vesicles, single channels can be studied. PMID- 2580575 TI - [Changes in the substance P content of the blood and hypothalamus during experimental emotional stress]. AB - A study was made of the content of substance P in the blood and hypothalamus of Wistar rat brain in acute and chronic emotional stress and after intraperitoneal injection of substance P in a dose of 250 mg/kg. A possibility was demonstrated of inducing long-term changes in the content of substance P in the hypothalamus after a single injection. Exposure to a single 24-hour stress was followed by an increase in the substance P content in the hypothalamus. PMID- 2580576 TI - [Blockers of the uncoupling action of caffeine on the Ca2+-transport function of sarcoplasmic reticulum membranes]. AB - The influence of caffeine on the efficiency of Ca2+ transport in the presence of oxalate by different fractions of sarcoplasmic reticulum (SR) membranes from rabbit skeletal muscle was studied. It was shown that caffeine (5 mM) decreases 4 fold the value of the Ca/ATP ratio in terminal cisterns of the SR without having any appreciable influence on the efficiency of Ca2+ transport by the light fraction of the SR. The uncoupling effect of caffeine is completely blocked by ruthenium red and by the local anesthetics, tetracaine, procaine, and benzocaine. PMID- 2580577 TI - [Immunochemical determination of placenta-specific and interorganic antigens in placental extract and blood serum in pregnant rats]. AB - It has been demonstrated that placenta extract of rats contains up to 14 antigens. Moreover, 11 of them are interorgan proteins of wide and limited specificity, two antigens (alpha 1- and alpha 2-globulins) are attributed to acute-phase proteins typical for pregnancy. beta 1-Globulin is a specific protein of rat placenta. The content of these antigens in blood serum increases with pregnancy and reaches a maximum toward the delivery; 3-4 days after delivery beta 1-globulin disappears completely from maternal blood, whereas the concentration of acute-phase proteins drops to the initial level. PMID- 2580578 TI - [Determination of monoclonal antibody specificity by mixed precipitation ingel]. AB - The enzyme-immunodiffusion technique is advanced which permits testing monoclonal antibodies included in the precipitate line formed in gel by polyclonal antibodies with the corresponding antigen. Rat or mouse monoclonal antibodies were mixed with polyclonal rabbit antiserum to the antigen at issue. The precipitate formed by immunogen and rabbit polyclonal antibodies included monoclonals. PMID- 2580579 TI - [Chemotherapy by ambulatory continuous infusion using a portable pump: a feasibility trial]. AB - 43 metastatic cancer patients received 190 portable infusors over 24 hours or more. This portable infusor is a disposable material made by Travenol which operates without outside energy. The drug in an elastomere balloon reservoir is injected about 24 hours at a rate of 2 ml/hour. We used various drugs: CDDP, bleomycin, 5 fluorouracil, aracytine, velbe, voltarene. The patients were under hospital observation and received their treatment without any incident due to the pump itself. The patients who had already been perfused with the usual technique greatly appreciated the comfort of this light portable device. Our next step will permit us to estimate the use of these infusors by patients at home. PMID- 2580580 TI - Competitive antagonism at thromboxane receptors in human platelets. AB - The inhibitory effects of three prostanoid analogues, EP 045, EP 092 and pinane thromboxane A2 (PTA2), on the aggregation of human platelets in vitro have been investigated. In diluted platelet-rich plasma (PRP), EP 045 (20 microM) and EP 092 (1 microM) completely inhibited irreversible aggregation responses to thromboxane A2 (TXA2), prostaglandin H2 (PGH2) and five chemically stable thromboxane mimetics, including 11,9-epoxymethano-PGH2 and 9,11-azo-PGH2. Reversible aggregation produced by the prostanoid analogue, CTA2, was also inhibited. The block of the stable agonist action was surmountable. In plasma free platelet suspensions EP 045 and EP 092 were more potent antagonists. Schild analysis indicated a competitive type of antagonism for EP 045 (affinity constant of 1.1 X 10(7) M-1); the nature of the EP 092 block is not clear. Primary aggregation waves induced by ADP, platelet activating factor (Paf) and adrenaline were unaffected by EP 045 and EP 092, whereas the corresponding second phases of aggregation were suppressed. Aggregation and 5-hydroxytryptamine (5-HT) release induced by either PGH2 or 11,9-epoxymethano-PGH2 were inhibited in a parallel manner by EP 045. Inhibition of thromboxane biosynthesis is not involved in these effects. EP 045 and EP 092 did not raise adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels in the platelet suspensions. In plasma-free platelet suspensions PTA2 produced a shape change response which could be blocked by EP 045. PTA2, therefore, has a thromboxane-like agonist action. The block of the aggregatory action of 11,9-epoxymethano-PGH2 by PTA2 appears to be mainly due to competition at the thromboxane receptor. However, PTA2 produced a slight rise in cyclic AMP levels; this could be due to a very weak stimulant action on either PGI2 or PGD2 receptors present in the human platelet. Functional antagonism by PTA2 may therefore augment its thromboxane receptor blocking activity. The results are discussed in terms of (a) the specificity of antagonism produced by EP 045, EP 092 and PTA2, (b) the validity of affinity constant determinations for receptor antagonists when aggregation is the biological response, and (c) the characteristics of the human platelet thromboxane receptor in comparison with those of thromboxane receptors in smooth muscle. PMID- 2580581 TI - The role of substance P as a neurotransmitter in the reflexes of slow time courses in the neonatal rat spinal cord. AB - In order to reveal the spinal reflexes involving the transmitter action of substance P (SP), the effects of capsaicin and an SP antagonist on the isolated spinal cord of the neonatal rat studied. When a single shock stimulus was given to a dorsal root (L3-L5) or a sciatic nerve, depolarizing responses of various time courses were recorded extracellularly from both ipsi- and contra-lateral ventral roots of the corresponding segments. The reflex response recorded from the contralateral ventral root consisted of fast and slow components, which will be referred to as contralateral fast and slow ventral root potentials (v.r.ps). The latter contralateral slow v.r.p. had a time-to-peak of 2-5 s and lasted 10-30 s. The threshold for the contralateral slow v.r.p. was about two times higher than that for the monosynaptic reflex, and it coincided with the threshold for activating the slow-conducting afferent fibres. The contralateral slow v.r.p. was abolished after the spinal cord was treated with capsaicin (1 microM for 30 min) in vitro. The contralateral slow v.r.p. was absent in the spinal cord derived from 4-day-old rats that had received capsaicin (50 mg kg-1, s.c.) on the 2nd day of life. The contralateral fast v.r.p. and other reflexes of fast time courses remained unaltered after treatment with capsaicin in vitro or in vivo. Administration of an SP antagonist, [D-Arg1, D-Pro2, D-Trp7,9 Leu11]-SP in concentrations of 5-16 microM depressed the contralateral slow v.r.p., but did not affect the monosynaptic reflex, the dorsal root potential and the contralateral fast v.r.p. [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP (5 microM) markedly depressed the SP-induced depolarizing response recorded from the ventral root whereas the responses to noradrenaline, 5-hydroxytryptamine, neurotensin and thyrotrophin releasing hormone (TRH) were unaffected by the SP antagonist. The response of the ventral root to acetylcholine was slightly depressed by the antagonist. The SP antagonist at 5-10 microM did not exert any agonist action on the motoneurones. The present results in conjunction with those of previous studies support the hypothesis that SP released from certain primary afferent fibres acts as a neurotransmitter, producing in dorsal horn neurones slow excitatory postsynaptic potentials which lead to the generation of the contralateral slow v.r.p. PMID- 2580582 TI - A behavioural and biochemical study in mice and rats of putative selective agonists and antagonists for 5-HT1 and 5-HT2 receptors. AB - Radioligand binding techniques have demonstrated the existence of 5 hydroxytryptamine (5-HT) binding subtypes: 5-HT2, 5-HT1A and 5-HT1B. These techniques have also indicated that certain drugs appear to show sub-type specificity: 8-hydroxy-2-(di-n-propylamino)tetralin(8-OH-DPAT), a 5-HT1A agonist; 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1-H indole (RU 24969), a 5-HT1B agonist; and ritanserin, a 5-HT2 antagonist. (-)-Propranolol is a 5-HT1 antagonist of uncertain sub-type specificity. An examination has been made in mice and rats of the behavioural and biochemical effects of these drugs to determine whether the binding sites have physiological functions and further characterise the behavioural models. Administration of carbidopa (25 mg kg-1) plus 5-hydroxytryptophan (100 mg kg-1) produced head-twitch behaviour in mice which was antagonized by ritanserin (ED50 = 65 micrograms kg-1) but not (-) propranolol (20 mg kg-1). 8-OH-DPAT (1-10 mg kg-1 s.c.) and RU 24949 (5 mg kg-1 i.p.) did not produce head-twitch behaviour. 8-OH-DPAT decreased 5-HTP- but not 5 methoxy-N-N-dimethyltryptamine (5 mg kg-1)-induced head-twitch by a (-) propranolol-insensitive mechanism. Locomotor activity produced in mice by RU 24969 (3 mg kg-1) was antagonized by (-)-propranolol (20 mg kg-1) but not the (+) isomer. (-)-Propranolol did not antagonize the behaviour induced in rats. In mice, both 8-OH-DPAT and RU 24969 markedly inhibited whole brain 5-HT synthesis and this effect was not antagonized by (-)-propranolol. In rats, 8-OH-DPAT (3 mg kg-1 s.c.) produced all the behavioural changes seen after quipazine (25 mg kg 1). (-)-Propranolol inhibited the behaviour changes produced by both agonists, while ritanserin antagonized the behaviour produced by quipazine but not 8-OH DPAT. It is concluded, therefore, that the 5-HT1A receptor exists between the 5 HT2 receptor and the behavioural effectors. 8-OH-DPAT (at 20 degrees C ambient temperature) rapidly decreased rat body temperature, an effect antagonized by (-) propranolol but not ritanserin. Quipazine (at 27 degrees C ambient temperature, but not 20 degrees C) increased body temperature but the effect was not blocked by either antagonist. Ritanserin does not antagonize apomorphine-induced locomotion in either species. 9 We suggest that 5-HT-induced head-twitch behaviour in mice is a useful 5-HT2 receptor model and the temperature change following 8-OH-DPAT injection in rats may be a 5-HT,A model. While (-)- propranolol antagonizes 8-OH-DPAT effects in rat, it does not inhibit 8-OH-DPAT effects in mice, and instead antagonizes RU 24969-induced locomotion. Its status as a 5-HT, antagonist remains illdefined. PMID- 2580584 TI - A study of 250 patients referred to a department of psychiatry for the deaf. AB - 250 patients referred to a department of psychiatry for the deaf were selected by random sampling and studied. The results underline the need for specialised services for deaf patients of all types, not only those who communicate solely by manual methods. Patients are referred to this department suffering from mental illness and communication disorders, as well as from problems related to their deafness. Some of the difficulties of managing a supra-regional service are discussed. PMID- 2580583 TI - Effects of neonatal antithyroid treatment on brain [3H]-imipramine binding sites. AB - The action of the antithyroid, sulphydryl reagent methimazole (MMI) on the specific binding of [3H]-imipramine in the cerebral cortex and corpus striatum of immature and mature rats has been examined. Chronic administration of MMI through the first 30 days of life decreased the number of imipramine binding sites in cortical but not striatal membranes, as assessed 48 h after the last injection of goitrogen. A similar treatment did not affect the binding profile of [3H] imipramine in mature rats. Acute administration of MMI to 30 day-old rats increased the number of imipramine binding sites shortly after the injection, an effect no longer evident 48 h later. MMI in vitro increased the binding of [3H] imipramine. It is concluded that maturational impairment of the hypothyroid cortex, rather than any alteration of membrane bound thiol groups, was a major cause for the diminished binding of [3H]-imipramine in MMI-treated, immature rats. PMID- 2580585 TI - Transurethral resection of the prostate and bladder neck incision: a review of 700 cases. AB - Transurethral resection (TUR) is regarded as the treatment of choice for relief of outflow tract obstruction in the male, but bladder neck incision (BNI) is an acceptable alternative when the gland is small. Seven hundred cases of TUR/BNI have been reviewed (TUR = 388; BNI = 312). BNI was performed when the gland was less than 35 g and where there was no clinical suspicion of malignancy. The operative details of our single incision technique are given. While the patients in the BNI group were younger, catheter stay was shorter, there was less infection, a significantly reduced need for blood transfusion and a satisfactory outcome in terms of control and need for further surgery. BNI is a technically simpler procedure than TUR and is easy to teach and learn. Results show it is safe and effective for patients in acute retention as well as those treated electively and it is the operation of choice for small benign prostates. PMID- 2580586 TI - Post-treatment fertility in patients with testicular cancer. I. Influence of retroperitoneal lymph node dissection on ejaculatory potency. AB - "Dry ejaculation" occurred in none of 15 patients with testicular cancer treated by right-sided retroperitoneal lymph node dissection (RLND). After left-sided and bilateral RLND, "dry ejaculation" was observed in 7/21 and 51/61 men respectively. Twelve of 21 patients with "dry ejaculation" or small volumes of seminal fluid had true retrograde ejaculation. In 7 of 10 men the ejaculatory volume increased significantly after treatment with imipramine chloride. Four men impregnated their wives during treatment with the drug. Without impairing the results of therapy it is possible to spare fibres from the sympathetic chains and pre-sacral plexus during RLND due to testicular cancer, thus preserving fertility in at least 40% of patients. PMID- 2580587 TI - Post-treatment fertility in patients with testicular cancer. II. Influence of cis platin-based combination chemotherapy and of retroperitoneal surgery on hormone and sperm cell production. AB - Active sperm production was observed in 20 of 35 patients with testicular cancer 1 year after discontinuation of all treatment (retroperitoneal surgery only: 13; cis-platin-based chemotherapy (CVB) +/- other treatment: 22). The percentage of patients who regained spermatogenesis increased slightly after a further 1 to 2 years. Fourteen patients (of 121 under observation) impregnated their wives (after retroperitoneal surgery: 9; after CVB +/- other therapy: 5). The individual serum FSH values correlated significantly with the results of sperm analysis: an FSH value greater than or equal to 20 iu/l indicated azoospermia in 8 of 12 patients, whereas only 5 of 30 patients with FSH levels less than or equal to 12 iu/l were azoospermic. Serum testosterone and pituitary serum LH were virtually unaffected by the treatment. In conclusion, 1 to 3 years after cis platin-based multi-modality treatment for testicular cancer, 50 to 60% of patients have active spermatogenesis and fatherhood can be achieved by a significant number of them. PMID- 2580588 TI - Hepatic resection in the treatment of hepatocellular carcinoma: report of 60 cases. AB - During the last 3 years and 9 months, hepatic resections were carried out on 60 patients with hepatocellular carcinoma (HCC). The resections were radical in 44 and palliative in 16 cases. Simultaneous operations were performed for oesophageal varices in 11 (9 prophylactic and 2 therapeutic) and for cholelithiasis in 9 patients. Fifty-nine patients had underlying hepatic disease; 52 had cirrhosis and 7 chronic hepatitis. Operative mortality rate within 1 month was 10 per cent and overall hospital mortality rate was 16.7 per cent. Excluding operative and hospital deaths, 76.8 per cent of patients who had radical excision and 18.8 per cent with palliative resections are alive. The result indicates that HCCs are frequently resectable even in the presence of liver cirrhosis provided that they are discovered at a relatively early stage. PMID- 2580590 TI - Effect of phenytoin on intracellular calcium and intracellular protein changes during pentylenetetrazole-induced bursting activity in snail neurons. AB - Effects of phenytoin (PHT) on the intracellular calcium and intracellular protein changes during pentylenetetrazole (PTZ)-induced bursting activity in the neurons of the Japanese land snail Euhadra peliomphala were examined. In the examination with a computer controlled electron probe X-ray microanalyzer, PHT clearly inhibited the intracellular calcium shift induced by PTZ as well as the calcium binding state change near the cell membrane. PHT also clearly inhibited the intracellular protein changes induced by PTZ. PHT, however, did not show any change in the transmembrane ionic currents such as the sodium current, calcium current and potassium current. These findings suggest that one of the main sites of anticonvulsant action of PHT is pathologically changed intracellular calcium movement and intracellular protein changes during seizure discharge. PMID- 2580589 TI - Screening of patients with retinitis pigmentosa for heredopathia atactica polyneuritiformis (Refsum's disease). PMID- 2580591 TI - Vasoactive intestinal polypeptide identified in the thoracic dorsal root ganglia of the cat. AB - Neurons which exhibited vasoactive intestinal polypeptide (VIP) immunoreactivity were identified with immunohistochemical techniques in the cat thoracic dorsal root ganglia (DRG, T8-T11) injected with colchicine 2 days prior to sacrifice. VIP-positive cells (5-40 cells per section) were small to medium size ranging from 14-41 micron in diameter. VIP-immunoreactivity was weaker in the thoracic DRG exposed to colchicine by topical administration. The neuropeptide could not be detected in the thoracic DRG (T1-T13) in the absence of colchicine. VIP immunoreactivity was also identified in the superficial laminae (I and II) of the thoracic spinal cord. The findings indicate that VIP in afferent pathways in the cat is distributed more extensively than previously reported and is not restricted only to the lower lumbar and sacral levels of the spinal cord. PMID- 2580592 TI - Coexistence of calcitonin gene-related peptide and substance P-like peptide in single cells of the trigeminal ganglion of the rat: immunohistochemical analysis. AB - The localization of calcitonin gene-related peptide (CGRP) and substance P (SP) in the rat trigeminal ganglion was examined by means of the indirect immunofluorescent method. About 40% of neurons in the ganglion contained CGRP like immunoreactivity (CGRPI), while about 20% of neurons showed SP-like immunoreactivity (SPI). In serial sections, nearly all the SPI neurons contained CGRPI. PMID- 2580593 TI - A presynaptic site of action of substance P and vasoactive intestinal polypeptide on myenteric neurons. AB - Substance P, vasoactive intestinal polypeptide, potassium and veratrine stimulated release of acetylcholine from isolated myenteric varicosities of guinea pig small intestine. Only the effect of veratrine was blocked by tetrodotoxin. The neuronal topography and action of these neuropeptides indicate a major cholinergic modulatory role for them in the myenteric plexus. PMID- 2580594 TI - The acute and chronic effects of capsaicin on slow excitatory transmission in rat dorsal horn. AB - The acute and chronic effects of capsaicin on rat spinal dorsal horn neurons and the excitatory transmission in the dorsal horn were investigated by means of intracellular recording techniques in the spinal cord slice preparation. Bath application of capsaicin (1-2 X 10(-5) M) produced in a majority of cells a prolonged depolarization associated with an increase in synaptic activity and intense neuronal discharges. During and immediately following the capsaicin depolarization, repetitive stimulation of a dorsal root failed to elicit the slow depolarization. After neonatal capsaicin treatment the proportion of dorsal horn neurons exhibiting the slow excitatory transmission was markedly reduced, however, the fast excitatory postsynaptic potentials were present in all examined cells. In addition, the proportion and sensitivity of the cells responding with a slow depolarization to substance P increased. PMID- 2580595 TI - Transganglionic regulation of central terminals of dorsal root ganglion cells by nerve growth factor (NGF). AB - Blockade of axonal transport or transection of the rat sciatic nerve results in transganglionic degenerative atrophy (TDA) of nerve terminals containing fluoride resistant acid phosphatase (FRAP) in the Rolando substance of the spinal cord. Application of vinblastine (9 micrograms) in a cuff around the sciatic nerve of adult rats blocked the retrograde transport of [125I]NGF in sensory fibers; this amount of vinblastine is identical to the threshold amount that induces TDA. Conversely, application of NGF to the proximal stump of the transected sciatic nerve prevented or delayed the occurrence of TDA as reflected by the maintenance of FRAP in the upper dorsal horn, that otherwise would inevitably disappear following the peripheral nerve lesion. These results suggest that endogenous NGF transported retrogradely in peripheral sensory fibers of the adult rat under normal conditions may be responsible for the regulation of the structural and functional integrity of the central terminals of these FRAP-containing primary sensory neurons and that TDA may be the consequence of the failure of NGF to reach the perikarya of these neurons. PMID- 2580596 TI - Antigenic differences among the voltage-sensitive sodium channels in the peripheral and central nervous systems and skeletal muscle. AB - Antisera prepared against the voltage-sensitive sodium channel purified from rat brain are able to distinguish antigenic differences between the sodium channels in peripheral nerve tissue, the central nervous system, and in skeletal muscle. These results indicate that, in spite of many well-documented similarities among the sodium channels of all excitable tissues, there are biochemical differences that may prove important in future studies of the regulation and molecular mechanisms of electrical excitability. PMID- 2580597 TI - Interstitial potassium concentration, slow depolarization and focal potential responses in the dorsal horn of the rat spinal slice. AB - Extracellular potassium concentration ([K+]o) was measured, and intra- and extracellular recordings made, in the dorsal horn of rat spinal cord slices maintained in vitro during repetitive dorsal root stimulation. In about half of the dorsal horn neurons, the stimulation evoked a possibly substance P-mediated slow depolarization. [K+]o increased during stimulation, reaching its highest values approximately 150 micron from the dorsal surface. The time course of delta [K+]o was different from that of the slow depolarization. Substance P itself evoked a much smaller delta [K+]o (0.4 mM) in the dorsal horn. It is concluded that the slow depolarization is not mediated by elevated [K+]o. PMID- 2580599 TI - An immunocytochemical study of the distribution of some plasma proteins within the developing forebrain of the pig with special reference to the neocortex. AB - The distributions of 4 plasma proteins (fetuin, transferrin, alpha-fetoprotein and albumin) have been studied by means of immunocytochemistry in the forebrain of the pig from 20 to 109 days of gestation, term being at 114 days. These proteins are present in plasma, cerebrospinal fluid, meninges, some epithelial cells of choroid plexus and some neural cells and processes. The most striking observation is that these proteins are excluded from the brain to a large extent even at the earliest ages. Fetuin is present early in gestation in a few cells bordering the ventricle. Fetuin-positive cells are subsequently seen principally in the newly formed cortical plate and later in the subplate zone. This suggests that fetuin may be acting as a signal for the early migrating cells of the cortex and that its presence is necessary to these cells, particularly as there appears to be an increase in the amount of fetuin in these same cells in mid-gestation at a time when many fibres are arriving in this region to make cortical connections. Late in gestation after connectivity, it has been established that there are few fetuin-positive neurons remaining. However, at this late stage many neurons are strongly positive for transferrin, for which they have been negative earlier. This appearance may be related to the onset of activity. Alpha-fetoprotein has a distribution similar to that of fetuin. Albumin, although present transiently in the cerebrospinal fluid in the middle of gestation, is not seen in neural cells within the cortex. There has been some controversy as to whether these proteins which have been reported to be present in the brains of other species have been synthesized by neural cells or been taken up by specific mechanism. This study suggests that during the course of brain development, both processes may play their part. PMID- 2580598 TI - Serotonin release in human cerebral cortex and its modulation via serotonin receptors. AB - Human cerebral cortex slices were prepared from brain tissue which had to be removed in order to gain access to deep-seated tumours. Subsequent to incubation with [3H]serotonin, the slices were superfused with physiological salt solution containing paroxetine, and 3H overflow was evoked by electrical field stimulation. The evoked tritium overflow (86% of which was accounted for by unmetabolized [3H]serotonin) was abolished by tetrodotoxin or omission of calcium from the superfusion fluid. Unlabelled serotonin decreased, and the serotonin receptor antagonist metitepin increased, the evoked overflow. The inhibition produced by serotonin was antagonized by metitepin. It is concluded that serotonin release in human cerebral cortex is modulated by inhibitory serotonin receptors, which may be localized presynaptically on the serotoninergic nerve fibers themselves. There are marked similarities between human and rat brain cortex with respect to action potential-induced, Ca2+-dependent serotonin release and its modulation via serotonin receptors. PMID- 2580601 TI - Facilitation of kindling in adult rats following neonatal exposure to lindane. AB - Neonatal male rats were exposed to lindane or corn oil directly by gavage or indirectly by maternal exposure. All surviving offspring were implanted with amygdaloid electrodes 90 days after weaning. Amygdaloid kindling began 10 days later using standard procedures. Neonatal lindane-exposed rats kindled significantly faster (9.9 +/- 0.5 days) than control groups (11.2 +/- 0.5 days). Lindane-exposed rats tended to have longer and more severe seizures than did non exposed rats on each trial during kindling acquisition. These findings demonstrate that high exposures of lindane during development can lead to enduring changes in the nervous system that facilitate adult kindling. PMID- 2580600 TI - Cerebrospinal fluid (CSF) and brain monoamine metabolites in the developing rat pup. AB - Concentrations of the neurotransmitters, serotonin (5-HT), dopamine (DA), and norepinephrine (NE) were measured in the developing rat brain at 12, 19, 26 and 42 days of age. The amino acid precursors, tryptophan (TRP) and tyrosine (TYR) were measured along with the 5-HT and DA metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), in brain and cerebrospinal fluid (CSF) at the above ages. This first report of CSF HVA levels in the developing rat shows that it, like 5-HIAA, declines with age. In contrast, the ontogeny of the compounds in brain are dissimilar, with 5-HIAA remaining relatively constant with age while HVA declines markedly. Possible reasons for the differences and similarities in the ontogeny of 5-HIAA and HVA levels in brain and CSF are discussed. The persistence of the ontogenetic pattern for the neurotransmitters and acid metabolites after central DA depletion is also reported. PMID- 2580602 TI - Changes in the ratio of two separate toxin binding sites on the sodium channel protein during rat brain development. AB - The development of two separate toxin binding sites from sodium channels of rat brain was studied. Whereas [3H]saxitoxin binding developed gradually, reaching adult levels by 4.5 weeks after birth, the binding of [125I]scorpion toxin increased rapidly for the first 10 days after birth, then declined. The stoichiometric ratio of [3H]saxitoxin binding site to [125I]scorpion toxin binding sites changed during development from 0.5 in 8 day old rats to 1.9 in adult rats, implying separate biological regulation for each of these sites. PMID- 2580604 TI - 12-O-tetradecanoyl-phorbol-13-acetate-induced differentiation of human neuroblastoma cells is not accompanied by an increase in the intracellular concentration of cyclic AMP. AB - Cultured human SH-SY5Y neuroblastoma cells could be induced to differentiate morphologically and biochemically followed by growth inhibition, by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The cells showed a limited differentiation when treated with substances known to increase the intracellular concentration of cyclic AMP. When these substances were combined with TPA, morphological differentiation and growth inhibition of the cells were potentiated. In contrast, these substances inhibited the TPA-induced increase in noradrenaline concentration and the relative activity of neuron-specific enolase. Both the intracellular concentration of cyclic AMP and the cytosolic level of cyclic AMP-binding components were similar in control and TPA-treated cells. It is suggested that cyclic AMP has a limited and non-regulatory role in the initiation of differentiation of SH-SY5Y cells. The effect of cyclic AMP is probably coupled mainly to the polymerization of microtubules, thus enhancing the morphological differentiation of the cells. PMID- 2580603 TI - Ontogenetic alterations in the effects of food and/or maternal deprivation on 5 HT, 5-HIAA and 5-HIAA/5-HT ratios. AB - Sprague-Dawley rat pups were deprived of food and/or the dam in experiment 1 for 24 h prior to sacrifice at 4, 10, 16 and 22 days postnatally and analysis of 5 HT, 5-HIAA and 5-HIAA/5-HT ratios in cortex, forebrain minus cortex, and brainstem. Deprivation was observed to increase indoles and their ratio early in life, with the most pronounced effects being observed in early maturing caudal brain regions of neonatal rat pups. These neurochemical effects of deprivation gradually diminished during ontogeny, becoming virtually absent by the age of weaning. In neonates, both deprivation from the dam and food appeared to influence indoleamine levels, whereas absence of food appeared to be primarily influential in older preweanling animals. Ambient temperature during the treatment period did not influence indoles or their ratio in 4- and 10-day-old rat pups, but did begin to influence indoles at 16 days postnatally, an age when homeothermia begins to develop. In experiment 2, it was observed that significant increases in indoleamines were not seen until 16 h of deprivation in 4-day-old rat pups deprived of food, and the dam for 0, 2, 4, 16 or 24 h prior to sacrifice. Possible functional implications of these deprivation-related increases in indoleamines early in ontogeny are discussed. PMID- 2580605 TI - Ontogeny of substance P-containing fibers in the taste buds and the surrounding epithelium. I. Light microscopic analysis. AB - Ontogeny of the substance P-like immunoreactive (SPI) structures in the circumvallate papillae of the rat taste buds was examined by means of indirect immunofluorescence method. SPI fibers in the lamina propria first appeared at gestational day 20, and their quantity increased up to postnatal day 10. On the other hand, SPI fibers in the epithelium were first seen on gestational day 21 and in the taste buds at postnatal day 2-4. These fibers increased remarkably in number after postnatal day 5 and reaching their maximum at postnatal day 20, and thereafter numbers decreasing slightly. PMID- 2580606 TI - The postnatal development of norepinephrine-stimulated cyclic AMP accumulation in rat spinal cord. AB - Norepinephrine (NE) stimulated cyclic adenosine 3',5'-monophosphate (cyclic AMP) accumulation in regional spinal cord and cortical tissue slices from postnatal rats demonstrated distinct developmental patterns. NE-concentration-response studies using a 10-min incubation period demonstrated minimal NE-stimulated cyclic AMP accumulation in whole spinal cord at PD 1-5 with maximal sensitivity on PD 12. Thereafter, sensitivity decreased to adult values at PD 30. Sensitivity changes were reflected in alterations in maximal response only since NE EC50s all averaged 10(-6) M. This agrees with no change in calculated Kd for NE with increased Vmax to PD 12 and a reduction thereafter. Studies on regional spinal cord and cerebral cortical cyclic AMP accumulation indicated peak NE sensitivity in cervical and thoracic cord occurred at PD 10, in lumbar cord at PD 15, and in cerebral cortex at PD 20. The fact that inhibition of phosphodiesterase (PPDE) produced the same percentage alteration in peak accumulation in spinal cord slices regardless of postnatal age suggests that PPDE is not the primary determinant of the ontogenic changes. The results indicate that the postnatal development of spinal NE receptors may be reflected in an increase in the responsiveness of the cyclic AMP system to NE. PMID- 2580608 TI - [The effect of procaine on calcium channels and excitation- contraction coupling of muscle membranes with calcium electrogenesis]. PMID- 2580607 TI - Cholinergic systems in the rat brain: II. Projections to the interpeduncular nucleus. AB - The cholinergic innervation of the interpeduncular nucleus was investigated by use of fluorescent tracer histology in combination with choline-O acetyltransferase (ChAT) immunohistochemistry and acetylcholinesterase (AChE) pharmacohistochemistry. Following propidium iodide or Evans Blue infusion into the interpeduncular nucleus, brains were processed for co-localization of transported fluorescent label and ChAT and AChE. Control infusions of tracers were made into the ventral tegmental area. In order to delimit the course of putative cholinergic afferents to the interpeduncular nucleus from extra habenular sources, knife cuts surrounding the habenular nuclei were performed. Somata containing propidium iodide that were highly immunoreactive for ChAT were found primarily in the vertical and horizontal limbs of the diagonal band, the magnocellular preoptic area, and the dorsolateral tegmental nucleus, also referred to as the laterodorsal tegmental nucleus. A few such co-labeled somata were also detected in the medial septal nucleus, substantia innominata, nucleus basalis, and pedunculopontine tegmental nucleus. A good correlation was observed between intensely-staining, AChE-containing and ChAT-positive neurons projecting to the interpeduncular nucleus from the aforementioned structures. Although the medial habenula contained numerous cells demonstrating transported label following interpeduncular infusion of fluorescent tracers, the ChAT-positivity associated with somata in that nucleus was weak compared to ChAT-like immunoreactivity in known cholinergic neurons in the basal forebrain and brainstem. Knife cuts that separated the habenular nuclei from the stria medullaris and neural regions lateral and posterior to those nuclei while leaving the fasciculus retroflexus intact resulted in a reduction of ChAT-like immunoreactivity in the medial habenular nucleus, fasciculus retroflexus, and interpeduncular nucleus. These data suggest (1) that the cholinergic innervation of the interpeduncular nucleus derives primarily from ChAT-positive cells in the basal forebrain and dorsolateral tegmental nucleus and (2) that putative cholinergic fibers having their origin in the medial habenula, if they exist, constitute a minor portion of the cholinergic input to the interpeduncular nucleus. PMID- 2580609 TI - [The effect of substitution hemodilution on pulmonary hemodynamics and the internal environment]. PMID- 2580610 TI - Analysis of high-resolution R-bands, obtained by heat-denaturation and Giemsa staining, on human prophase chromosomes. AB - RHG-bands (heat-denatured Giemsa R-bands) of human prophase chromosomes were analyzed at high resolution, and the banding patterns at prophase and metaphase are presented. The bands were compared with those of the International Standard Cytogenetic Nomenclature idiograms and of the G-band idiograms proposed by J. J. Yunis. The number, size, and position of the RHG-bands correspond rather well with their equivalent G-negative bands, but some differences were noted in the zones of preferential stretching, the juxtacentromeric regions, and the telomeres. Variations in the centromere index and the banding pattern in heterochromatin were also discussed. PMID- 2580611 TI - Chlormadinone acetate, a progesterone derivative that binds to the digitalis receptor, inhibits the sodium pump in the isolated rat diaphragm. AB - Rb+ uptake, intracellular Na+ and K+ levels, and the tissue-medium distribution of the nonmetabolized glucose analog, 3-O-methyl-D-glucose (3-MG) were measured in rat diaphragms incubated with chlormadinone acetate, 6-chloro-4,6-pregnadien 17-ol-3,20-dione 17-acetate (CMA), in the presence and absence of ouabain. CMA in concentrations of 5 X 10(-7) M or higher significantly depressed 86Rb uptake, and promoted an increase in internal Na+ and a decrease in internal K+, indicating inhibition of the sodium pump. Sugar transport in resting muscle parallels the changes in internal Na+ levels and is an additional indicator of sodium pump activity. Equilibration of 3-MG between tissue and medium was accelerated by CMA, in parallel to the rise in internal Na+ level. Effects of CMA on Na+ levels and sugar transport, but not on Rb+ uptake, were additive to those of various concentrations of ouabain, suggesting interaction with sites not affected by ouabain. These results on diaphragm muscle confirm our previous studies on isolated cardiac muscle preparations showing that CMA, added to the aqueous bathing medium, inhibits the sodium pump in intact muscle tissues. PMID- 2580612 TI - Unusual potassium channels mediate nonadrenergic noncholinergic nerve-mediated inhibition in opossum esophagus. AB - Field stimulation of the circular muscle of the opossum esophagus produces a transient hyperpolarization (inhibitory junction potential, IJP) followed by an "off" depolarization. A similar nonadrenergic, noncholinergic (NANC) response in guinea pig taenia caecum has been shown to be due to an increase in the potassium ion permeability of the smooth muscle cell membrane. Double sucrose gap studies showed a decrease in resistance during the IJP, and a reversal at an estimated membrane potential of about -90 mV (4 mM K+). The reversal potential was dependent on the extracellular potassium concentration, shifting to -75 mV when the potassium in the superfusion medium was increased to 10 mM. The IJP in the opossum esophageal circular smooth muscle is therefore like the IJP of the guinea pig taenia caecum in that it is probably due to a selective increase in potassium ion permeability. Potassium conductance blocking agents, tetraethylammonium chloride (TEA, 20 mM) and 4-aminopyridine (4-AP, 5 mM) both caused a depolarization of the smooth muscle cell membrane, but TEA increased the membrane resistance, whereas 4-AP did not affect the membrane conductance in a consistent way. A decrease in IJP amplitude owing to these agents was not apparent. Apamin (10 microM) did not affect the membrane potential, the membrane resistance, or the IJP. Quinine (0.1 mM) produced effects quantitatively similar to those of TEA. Quinine (1 mM) did abolish the IJP, however, this was likely due to a blockade of impulse transmission of the intramural nerves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580613 TI - Antagonistic effect of polyinosinic-polycytidylic acid on the cell lethality produced by 5-fluorouracil in human colon carcinoma cells in vitro. AB - The effect of polyinosinic X polycytidylic acid [poly(I) X poly(C)] on the cell lethality produced by 5-fluorouracil [FUra] and 5-fluorouridine [FUrd] was examined in human colon carcinoma cell line HT-29. Pretreatment of cells with poly(I) X poly(C) as well as during exposure to FUra or FUrd resulted in antagonism of the cell lethality generated by the fluoropyrimidines. Antagonism of FUra cytotoxicity was also produced by the 2'-O-methylated analogue, polyinosinic X poly-2'-O-methylcytidylic acid, but not by the individual single stranded polynucleotides or by the component mononucleotides, cytidine 5' phosphate and inosine 5'-phosphate. In contrast, cytidine 5'-phosphate blocked the toxicity of FUrd. The antagonism by poly(I) X poly(C) of FUra and FUrd cytotoxicity was related to the inhibition of their metabolism to fluorouridine triphosphate and their incorporation into RNA and not to inhibition of the synthesis of RNA. Antibodies to leukocyte and fibroblast interferons did not reverse the antagonistic activity of poly(I) X poly(C). These results indicate that poly(I) X poly(C) may be interfering with the transport and/or initial metabolism of FUra and FUrd to fluorouridine monophosphate which is independent of the ability of the double-stranded RNA to induce interferon. PMID- 2580614 TI - Ultrarapid recovery from lethal effects of bleomycin and gamma-radiation in stationary-phase human diploid fibroblasts. AB - An ultrarapid phase of cellular recovery, as measured in liquid holding type experiments, was studied in stationary-phase human fibroblasts exposed to bleomycin or cobalt-60 gamma-irradiation yielding comparable levels of cell killing. This rapid recovery was both faster and considerably greater in magnitude after bleomycin treatments. Bleomycin survival curves were multiphasic, indicating the presence of treated cells with varying sensitivities either at the beginning of treatments or as a result of resistance which developed during the treatment period. The amount of both ultrarapid (within 2 to 10 min) and slower recovery was dose dependent after irradiation with 200 to 800 rads or 30-min exposures to bleomycin (5 to 100 micrograms/ml). Following bleomycin treatments resulting in surviving fractions of 1 to 2%, survival increased up to 8-fold after only 2 min of posttreatment incubation. This rapid increase in survival was followed by a slower increase over time periods up to 3 h. In contrast, the rates of cellular recovery after gamma-irradiation were more gradual from 0 to 3 h. Recovery at all posttreatment intervals was always greater after bleomycin than after gamma-treatments, following doses yielding 1 to 50% survival. The ultrarapid component of cellular recovery after bleomycin treatments may have implications for both clinical cancer management and cellular studies directed toward determining mechanisms of action of bleomycin. PMID- 2580615 TI - Rapid and slow DNA rejoining in nondividing human diploid fibroblasts treated with bleomycin and ionizing radiation. AB - The rejoining of DNA single-strand breaks produced after bleomycin treatment or gamma-irradiation of human diploid fibroblasts was studied by the alkaline elution technique. DNA rejoining occurred at slower rates in bleomycin-treated human fibroblasts than in gamma-irradiated fibroblasts. These comparisons were made at similar levels of survival or DNA single-strand breaks (including alkali labile lesions). Significant numbers of DNA single-strand breaks were detected routinely after 2 micrograms/ml (1.34 X 10(-6) M) bleomycin treatments (for 30 min, survival greater than 70%). Dose-dependent losses of approximately 3 to 15% of total radioactivity were measured in preelution samples from cells treated with bleomycin (2 to 100 micrograms/ml), but only 2 to 3.5% of total radioactivity was assayed in lysis samples from cells irradiated with 200 to 1000 rads. This result suggests that DNA was more degraded by or after bleomycin treatment. DNA was rejoined extremely rapidly after bleomycin or radiation treatments, and the rejoining was both agent- and dose-dependent. Over dose ranges yielding surviving fractions of 75 to 0.056%, considerable DNA rejoining occurred after only 2.5 min posttreatment incubation in conditioned medium. Cellular recovery occurred at faster rates after bleomycin treatments than after gamma-irradiation, while DNA rejoining occurred at faster rates after gamma irradiation, thus uncoupling DNA repair and cellular recovery in relating the cellular action of these 2 agents. No consistent differences were observed among 3 normal fibroblast strains and fibroblasts from a Gardner's syndrome patient (deficient in their capacity for cellular recovery) or a Turcot's syndrome patient in the formation and rejoining of single-strand breaks after bleomycin or radiation treatments. PMID- 2580616 TI - Lidocaine potentiation of bleomycin A2 cytotoxicity and DNA strand breakage in L1210 and human A-253 cells. AB - The survival of cultured L1210 cells exposed to bleomycin A2 (BLM A2) was markedly decreased by coincubation with the local anesthetic lidocaine. The potentiation occurred with concentrations of lidocaine that were nontoxic and was dependent upon both the concentration of lidocaine and BLM A2. A 1000-fold decrease in survival was seen with a 1-h exposure to 8 mM lidocaine and 10 microM BLM A2 compared to incubation with 10 microM BLM A2 alone. Prior exposure to lidocaine did not markedly alter BLM A2 cytotoxicity, while treatment with lidocaine immediately after BLM A2 exposure did, suggesting that increased cellular content of BLM A2 was not the mechanism of enhancement. Furthermore, lidocaine reduced the total amount of cell-associated radioactivity seen after incubation with [3H]BLM A2. The enhancement in L1210 cell cytotoxicity with lidocaine was not specific for the C- and N-terminal moieties of the BLM molecule. Other DNA-interacting antitumor agents, such as etoposide and mitomycin C, did not exhibit biologically significant alterations in their cytotoxicity when coincubated with lidocaine, although cis-diamminedichloroplatinum was significantly more toxic in the presence of lidocaine. The potentiation of BLM A2 cytotoxicity was not unique to murine tumor cells, since it was also seen with cultured human head and neck carcinoma (A-253) cells. Lidocaine did not increase directly BLM A2-induced breakage of DNA in vitro as measured by loss of form I pAT 153 DNA, but it did increase BLM A2-induced DNA strand breaks in intact L1210 cells coincubated with lidocaine and BLM A2. Exposure of L1210 cells to lidocaine after BLM A2 treatment also greatly increased DNA breakage consistent with possible inhibition of DNA repair. In addition, a modest reduction in the in vitro inactivation of BLM A2 by BLM hydrolase was found with lidocaine. We propose that inhibition of BLM metabolism and repair of BLM-induced DNA damage by lidocaine may have a role in the enhanced cytotoxicity. PMID- 2580617 TI - Effect of estramustine phosphate on the assembly of isolated bovine brain microtubules and fast axonal transport in the frog sciatic nerve. AB - Estramustine phosphate (0.01 to 0.5 mM), an estradiol mustard derivative used in the therapy of prostatic carcinoma, inhibited the assembly of brain microtubules proteins in vitro and disassembled preformed microtubules. In the presence of estramustine phosphate, the minimum microtubule-protein concentration sufficient for the assembly of microtubules was increased. Low concentrations of taxol (20 microM) completely reversed the inhibition of assembly by estramustine phosphate. The effects were specific to estramustine phosphate since neither estradiol 17 beta-phosphate, the hormonal moiety of the drug, nor nornitrogen mustard, the alkylating moiety, had any effect on assembly. Estramustine phosphate (0.1 to 0.5 mM) was also found to reversibly inhibit fast axonal transport in the frog sciatic nerve. The nerve content of adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate was not significantly affected by estramustine phosphate. Our results suggest that the cytotoxic action of estramustine phosphate could be dependent partially on an interaction with microtubules, probably via the microtubule-associated proteins. PMID- 2580619 TI - Histochemical and immunohistochemical characterization of surgically resected and heterotransplanted Wilms' tumor. AB - Nine surgically resected Wilms' tumors (WIT) and nude mouse heterotransplants from one WIT were studied by histochemistry and immunohistochemistry. Histochemistry showed acid phosphatase in all cells, while alkaline phosphatase and gamma-glutamyl transpeptidase were present in only some tubules. Using immunohistochemistry, antibodies to the intermediate filaments cytokeratin and vimentin distinguished tubular epithelium and mesenchyme, respectively. WIT tubules were also identified using antibody against a structural component (epithelial membrane antigen) and a secretory product (uromucoid) associated with distal convoluted tubules of normal kidney. Basement membrane surrounding the tubules of WIT was demonstrated using antibody to type IV collagen plus laminin. Different blastema subpopulations were negative or stained positively with antibodies to cytokeratin and vimentin. Production of basement membrane by blastema was also shown. Fetal antigen expression in WIT was examined using the monoclonal PI 153/3 and J5 antibodies. The blastema and tubules of WIT were strongly stained by PI 153/3, which did not label normal adult kidney, and weakly stained by J5, which strongly labeled glomeruli and proximal convoluted tubules of normal kidney. These studies show that WIT blastema is heterogeneous in intermediate filament subtypes, while WIT tubules more closely resemble distal than proximal convoluted tubules of adult kidneys but also retain expression of fetal antigens. PMID- 2580618 TI - Chromatin-associated protein kinases in human normal and benign hyperplastic prostate. AB - Nuclear phosphoproteins and protein kinases of human normal and benign hyperplastic prostate (BPH) were studied in an effort to delineate their properties and to identify any underlying differences therein. Chromatin associated protein kinases active towards phosvitin, lysine-rich histone, and endogenous nonhistone proteins were characterized in human prostatic nuclei. The general properties of the human chromatin-associated prostatic protein kinases were similar to those of rat ventral prostate chromatin. Polyamines stimulated the phosphorylation of endogenous nonhistone proteins and phosvitin. Protein kinases active towards phosvitin and lysine-rich histones were unaltered in chromatin from BPH tissue as compared with the normal prostate. However, phosphorylation of chromatin-associated nonhistone proteins was markedly enhanced (average, 123%) in BPH tissue as compared with the normal tissue. The results indicate a change in the protein kinase reaction specifically involving chromatin associated nonhistone proteins of BPH tissue as compared with normal human prostate. PMID- 2580620 TI - Identification of two different surface epitopes of human ovarian epithelial carcinomas by monoclonal antibodies. AB - Monoclonal antibodies (Mabs) against human ovarian mucinous and serous carcinoma were obtained by the Mab technique. Their reactivities against human tumors were tested by indirect immunofluorescence. One of the Mabs, named 4C7, derived from the spleen cells of mice immunized with mucinous carcinoma line OVA-1, reacted to ovarian mucinous carcinoma, endometrioid carcinoma, and mesonephroid carcinoma but did not react to ovarian serous carcinoma. Another Mab, 3C2, obtained from the spleen cells of mice immunized with serous carcinoma line HOC-21, reacted to serous carcinoma and endometrioid carcinoma of ovary, but never reacted to mucinous carcinoma or mesonephroid carcinoma. Neither of the Mabs reacted to other types of ovarian carcinomas such as undifferentiated carcinoma, dysgerminoma, endodermal sinus tumor, and malignant teratoma of ovary, and also did not react to any benign ovarian tumors or other normal human tissues. Both Mabs 3C2 and 4C7 had no reactivity to carcinoma of other organs such as stomach, colon, lung, lymphoid system, and kidney and also did not react to human lymphocytic or carcinoembryonic antigen as confirmed by using many human cell lines and surgically resected samples. Since the cross-reactivities of these Mabs were limited within the ovarian epithelial carcinomas, it is suggested that two distinct epitopes are expressed on the ovarian epithelial carcinomas. One epitope, identified by Mab 4C7, is expressed only on mucinous carcinoma, endometrioid carcinoma, and mesonephroid carcinoma, while the epitope, identified by Mab 3C2, appears only on serous and endometrioid carcinoma. PMID- 2580621 TI - Stimulation of haptotaxis and migration of tumor cells by serum spreading factor. AB - A central feature of tumor metastasis is the migration of malignant cells through interstitial tissues and vascular structures as they spread throughout the body. Various components of the extracellular matrix and of basement membranes, consisting of genetically distinct collagens, proteoglycans, and noncollagenous glycoproteins, are known to modulate certain aspects of cell behavior, including cell movement. Serum spreading factor is a glycoprotein component of human serum that is also found in interstitial tissues. Two native forms are seen in human serum, a Mr 65,000 and a Mr 75,000 component. Spreading factor promotes substratum attachment and spreading of diverse cell types, including epithelial and fibroblastic cells, and will affect the growth rate and differentiation of cells in serum-free culture media. Serum spreading factor was shown to promote the directed migration of the following tumor cell lines in modified Boyden chamber assays: murine melanoma K-1735 (clones M2, M4, and 16); human breast carcinoma MCF-7; and human fibrosarcoma HT-1080. The stimulation of movement occurred over a concentration range of 0.5 to 50 micrograms of serum spreading factor per ml with a maximum response between 5 and 10 micrograms/ml. The maximal response varied with the cell line and ranged from 5- to 50-fold greater migration than control. A monoclonal antibody to spreading factor, previously shown to inhibit the attachment and spreading-promoting activity, abrogated this migration response. Experiments using filters that were precoated with spreading factor indicated that cells could migrate on an insolubilized layer of this protein by haptotaxis. Tumor cell migration to spreading factor in vitro suggests a possible role for this protein in the phenotypic behavior of metastatic cells. PMID- 2580623 TI - Amplification of the antitumor activity of phleomycins and bleomycins in rats and mice by caffeine. AB - While having no antitumor effect per se, caffeine substantially enhanced the antitumor effects of the phleomycins PLM-CHP and PLM-PEP, and the bleomycins BLM CHP and Blenoxane in rats carrying Walker 256 carcinosarcoma and/or mice carrying Ehrlich ascites tumor, even at doses of phleomycin and bleomycin below the minimum effective level. Positive but less conclusive results were also obtained with PLM-A4A4G and PLM-G. PMID- 2580622 TI - Lymphokine-induced monocytic differentiation as a possible mechanism for hypercalcemia associated with adult T-cell lymphoma. AB - Patients with adult T-cell lymphoma frequently have hypercalcemia. Bone biopsies from these patients show increased numbers of osteoclasts. We hypothesized that substances produced by the malignant T-cell caused these phenomena by increasing the formation and/or activity of osteoclasts. To test this hypothesis, we cultured U937 cells in conditioned media from a clonal T-cell line derived from a patient with adult T-cell lymphoma and hypercalcemia. This conditioned media produced maturational changes in the U937 cells as evidenced by decreased proliferation, increased adherence, increased expression of complement receptors, and formation of multinucleated giant cells. These changes were synergistically enhanced by the addition of 1 alpha, 25-dihydroxyvitamin D3 which is known to promote monocyte differentiation. We also tested interleukin 2 and gamma- and alpha-interferon to see if they were responsible for the maturational changes. Although some effects were seen, these lymphokines could not account for all the changes induced by the T-cell conditioned media. These findings support the above hypothesis and suggest that other unidentified factors may promote the differentiation of osteoclast precursors and be involved in the pathogenesis of the hypercalcemia. PMID- 2580624 TI - Induction of highly immunogenic variants of Lewis lung carcinoma tumor by ultraviolet irradiation. AB - This study was undertaken to determine whether in vitro treatment of Lewis lung carcinoma (3LL) cells with ultraviolet (UV) radiation could increase their immunogenicity. Tumor cells were irradiated with UV light from a germicidal lamp (254 nm; UV-C) at a dose of 720 J/sq m. After 2 weeks of culture, the surviving cell population was cloned by limiting dilution. Cell suspensions of each clone were injected intrafootpad in C57BL/6 mice at a dose of 2.5 X 10(5) cells per mouse. Eighty independent clones were tested. Fifty-one clones showed decreased tumorigenicity and failed to grow in 20 to 95% of immunocompetent mice, whereas they produced tumors in 100% of irradiated (550 R) and athymic nude mice. These clones were designated "tum-" (nontumorigenic) clones. In contrast, all 25 clones selected from the untreated parental 3LL induced progressively growing tumors in 100% of the mice. After two courses of UV treatment, the uncloned 3LL population was rejected in 45% of inoculated mice. Mice rejecting an inoculum of a tum- clone were completely resistant to subsequent challenge with higher doses of the same or unrelated tum- clones. This resistance was fully expressed even after irradiation of immune mice with 550 R. Mice immune to a tum- clone also were able to prevent the growth of various tum+ clones or untreated 3LL tumor cells. When tum- and tum+ clone cells were simultaneously inoculated intrafootpad in opposite legs, rejection of tum- clone resulted also in the prevention of the growth of tum+ clone. Spleen cells of immune mice caused rapid elimination of radiolabeled 3LL tumor cells from the place of their inoculation (intrafootpad) and prevented tumor growth. In an in vitro cytotoxic assay, spleen cells after in vivo and in vitro immunization with tum- clones demonstrated high cytotoxic activity against various tum+ clones and parental 3LL cells, as well as against tum- clones. In addition, parental 3LL tumor cells and tum- cells were similarly able to inhibit cytotoxic activity in the cold target inhibition assay. However, in contrast to tum- cells, 3LL cells were less efficient in in vitro restimulation of cytotoxic activity of immune spleen cells. Therefore, these data suggest that tum-, tum+, and parental 3LL cells share a common antigenic specificity, which is not immunogenic in 3LL cells. UV treatment presumably converted the antigenic determinants present in the 3LL cells into an immunogenic form. PMID- 2580625 TI - Monoclonal antibodies to a glycolipid antigen on human neuroblastoma cells. AB - Using a somatic cell hybridization technique, four murine monoclonal antibodies (three immunoglobulin M and one immunoglobulin G3) were produced against a human neuroblastoma cell surface glycolipid antigen. They reacted strongly with all human neuroblastoma tumor-containing specimens and six of eight human neuroblastoma cell lines. More than 98% of each neuroblastoma cell population possessed this surface antigen, and in the presence of complement, 100% of them were killed. While melanoma and osteogenic sarcoma carried this antigen, leukemia and most Ewing's and Wilms' tumors did not. There was no cross-reaction with 30 normal or remission bone marrow samples and none with normal human tissues other than neurons in vitro. This antigen was neuraminidase sensitive, separable on thin-layer chromatogram, and did not modulate after combining with the monoclonal antibodies. These antibodies could detect less than 0.1% tumor cells deliberately seeded in the bone marrow samples. Because of their unique properties, these monoclonal antibodies may have diagnostic and therapeutic potentials. PMID- 2580626 TI - Two distinct tumor cell growth-inhibiting factors from a human rhabdomyosarcoma cell line. AB - Tumor cell growth-inhibiting factors (TIFs) have been shown to inhibit the growth of tumor cell lines in culture. TIF-1, the first TIF to be described, is a low molecular-weight, acid- and heat-stable polypeptide with no antiviral activity. A second class of TIFs (TIF-2) has now been isolated from the conditioned media of a human rhabdomyosarcoma cell line and partially purified by polyacrylamide gel filtration, cation exchange, and reverse-phase high-pressure liquid chromatography. Partially purified preparations of TIF-2 inhibit the growth of a variety of human tumor cells in soft agar and monolayer cultures and are mitogenic for normal human and mouse cells. TIF-2 has no antiviral activity. The growth-inhibitory effects of TIF-2 are reversible when the affected cells are no longer exposed to the factor. Although both TIF-1 and TIF-2 are obtained from the same source, they can be distinguished by their molecular weight, heat lability, elution pattern from reverse-phase high-pressure liquid chromatography, and their effect on the growth of mink lung epithelial cells. The growth of a human tumor cell variant, selected for resistance to growth inhibition by TIF-1, is inhibited by TIF-2. TIFs may therefore be a family of related polypeptides which selectively inhibit the growth of tumor cells. PMID- 2580627 TI - Heterogeneity of keratin expression in mouse mammary hyperplastic alveolar nodules and adenocarcinomas. AB - The keratins and other cytoskeletal proteins expressed by normal, preneoplastic, and malignant mammary tissues in BALB/c mice and by cells in primary cultures established from these tissues were analyzed and compared. The preneoplastic lesions were hyperplastic alveolar nodules (HAN) derived originally from mice treated by hormonal stimulation (D2), exposed to a chemical carcinogen (C4), or spontaneously expressing mouse mammary tumor virus (CV2) and maintained by serial transplantation. All tumors were mammary adenocarcinomas which developed as primary neoplasms from the HAN outgrowth lines. Cytoskeletal extracts were prepared from the tissues and cultured cells and subjected to two-dimensional polyacrylamide gel electrophoresis. Comparison of the major polypeptides in the normal and abnormal tissue extracts revealed considerable similarities in the cytoskeletal profiles. Three basic and seven acidic polypeptides ranging in molecular weight from 40,000 to 90,000 were regularly identified. However, notable differences were also found. A Mr 55,000 keratin (IEF 55) was prominent in one HAN, the D2, and all tumor tissues but not in normal gland. Likewise, a Mr 46,000 polypeptide (IEF 46), which has been tentatively identified previously as a keratin, was absent in normal epithelium but present in all abnormal tissues except the C4 and CV2 HAN. A Mr 58,000 polypeptide (NEPHGE 58) was not detected in normal gland or the C4 lesions but was found in all other abnormal tissues. The overall pattern of polypeptides in cytoskeletal extracts from normal and abnormal mammary cells in primary culture resembled that of the corresponding tissue but also had important differences. In all cell cultures, IEF 46 and IEF 55 were major species, while the larger and more basic components were markedly reduced. A Mr 56,000 polypeptide (NEPHGE 56) was detected only in C4 HAN and C4 and CV2 tumor cells. Trace or small, variable amounts of a Mr 57,000 basic keratin (NEPHGE 57) were present in normal and D2 tissues and cultured cells. NEPHGE 57 was dramatically increased in C4 and CV2 tissues and cultured cells and may be related to expression of squamous metaplasia and keratinization which are characteristic of these lesions. Although production of IEF 46 and IEF 55 may be associated with neoplastic progression of mammary epithelium, particularly in vivo, the association is not exclusive since normal cells express these polypeptides when grown in primary culture. In addition, correlations between altered keratin expression and the mode of induction of the mammary lesions were not obvious. PMID- 2580629 TI - Multistage-promotion and carcinogenesis studies in rat tracheal epithelial cells in culture. AB - In summary, two in vitro systems with rat tracheal epithelial cells were used to demonstrate that initiated respiratory tract epithelial cells can be promoted or enhanced to transform at a higher frequency by exposure to a noncarcinogenic tumor promoter. The latter two studies suggest possible mechanisms for this enhancement: 1) TPA amplifies the chromosomal instability brought about by initiating doses of carcinogen and 2) TPA alters gene expression and cellular differentiation such that it causes the initiated cell to escape the normal differentiation and senescence process thereby enhancing the proliferative lifespan of initiated cells. PMID- 2580628 TI - Experimental methods for the detection of the carcinogenicity and/or cocarcinogenicity of inhaled polycyclic-aromatic-hydrocarbon-containing emissions. PMID- 2580630 TI - Vascular permeability (problem of the blood-brain barrier) in the pineal organ of the rainbow trout, Salmo gairdneri. AB - The problem of the blood-brain barrier in the pineal organ of the rainbow trout, Salmo gairdneri, was investigated following intraperitoneal or intracardial injections of several tracers and dyes with different molecular weights. As demonstrated at the light-microscopic level, repeated injections of trypan blue or horseradish peroxidase (HRP) resulted in an accumulation of these substances in the pineal epithelium (parenchyma). By use of the electron microscope, HRP was found in electron-dense bodies, probably lysosomes, in the endothelial cells and perivascular macrophages 4 h after intraperitoneal injection, the supporting cells and intrapineal or luminal macrophages 8 h after injection, and the receptor cells 24 h after injection of the tracer. Ferritin particles penetrated the fenestrated endothelium of pineal capillaries. They were confirmed to vesicles, vacuoles and the smooth endoplasmic reticulum of the supporting cells as well as to the synaptic vesicles and the smooth endoplasmic reticulum of the pineal photoreceptors. The intercellular passage of tannic acid mixed with the fixative was blocked at the luminal junctional complex separating the pineal lumen from the basal portion of the pineal epithelium. The passive intercellular transport of substances with high molecular weight from the bloodstream to the cerebrospinal-fluid compartment is thus prevented. However, no blood-brain barrier exists for exogenously administered proteins, which are rapidly taken up by pineal cells and actively transported in a transcellular manner. The findings on the blood-brain barrier of the pineal organ of the rainbow trout are discussed with particular reference to the endocrine capacity of pineal sensory organs. PMID- 2580631 TI - Fine structure of growth cones in the upper dorsal horn of the adult primate spinal cord in the course of reactive synapto-neogenesis. AB - Following transganglionic degenerative atrophy of primary afferent terminals induced by a crush-injury of the sciatic nerve, a regenerative process takes places in the upper dorsal horn of the lumbar spinal cord in the primate Macacus rhesus. Axonal growth cones are characterized by cisterns of axoplasmic reticulum; filopodia emanating from growth cones are electron-optically translucent sheet-like expansions, often containing growth-cone vesicles. Axoplasmic reticulum appears also in preterminal portions of regenerating axons. Dendritic growth cones contain a fine, filamentous matrix; electron-dense membrane specializations can be seen in well-defined areas of their surfaces. Immature synapses are formed between filopodia of axonal growth cones and dendritic growth cones. Electron-microscopic structures of this unique CNS regeneration are similar to those seen in the course of embryonic development of the spinal cord. PMID- 2580632 TI - Video microscopy of fast axonal transport in extruded axoplasm: a new model for study of molecular mechanisms. AB - The development of AVEC-DIC microscopy and the application of this method to the study of fast axonal transport in isolated axoplasm extruded from the giant axon of the squid Loligo pealei provides a new paradigm for analyzing the intracellular transport of membranous organelles. The size of the axon, the number of transported particles, and the absence of permeability barriers like the plasma membrane in this preparation permit many experiments that are difficult or impossible to perform using other model systems. The use and features of this preparation are described in detail and a number of properties are evaluated for the first time. The process of extrusion is characterized. Particle movement is evaluated both in the interior of extruded axoplasm and along individual fibrils that extend from the periphery of perfused axoplasm. The role of divalent cations, particularly Ca2+, and the effects of elevated Ca2+ on axoplasmic organization and transport are analyzed. A series of pharmacological agents and polypeptides that alter cytoskeletal organization are used to examine the role of microfilaments and microtubules in fast transport. Finally, the effects of depleting ATP and of adding ATP analogues are discussed. The extruded axoplasm preparation is shown to be an invaluable model system for biochemical and pharmacological analyses of the molecular mechanisms of intracellular transport. PMID- 2580633 TI - In vitro translocation of organelles along microtubules. PMID- 2580634 TI - E. coli RNases: making sense of alphabet soup. PMID- 2580635 TI - Self-splicing of yeast mitochondrial ribosomal and messenger RNA precursors. AB - We have previously shown linear and circular splicing intermediates resembling intermediates that result from self-splicing of ribosomal precursor RNA of Tetrahymena to be present in mitochondrial RNA. Here we show that splicing of yeast mitochondrial precursor RNA also occurs in vitro in the absence of mitochondrial proteins. The large ribosomal RNA gene, consisting of the intron and part of the flanking exon regions, was inserted behind the SP6 promoter in a recombinant plasmid and was transcribed in vitro. The resulting RNA shows self catalyzed splicing via incorporation of GTP at the 5'-end of the excised intron, 5'- to 3'-exon ligation, and intron circularization. When purified mitochondrial RNA is incubated under similar conditions with alpha-32P-GTP, the excised ribosomal intron RNA is also labeled, as well as several other RNA species. Some of these RNAs are derived from excised introns from the multiply split gene coding for cytochrome oxidase subunit I. PMID- 2580636 TI - Meiosis-specific transcripts of a DNA component replicated during chromosome pairing: homology across the phylogenetic spectrum. AB - In meiotic cells of Lilium, a group of single or low copy number DNA sequences that constitute about 0.1-0.2% of the genome do not replicate during the premeiotic S-phase but do so at zygotene in coordination with chromosome pairing. An appreciable fraction of these sequences has now been found to be transcribed into poly(A)+ RNA when chromosomes initiate the pairing process. This "zygRNA" has not been detected in nonmeiotic tissues. Even within the meiocytes, zygRNA is not detectable prior to leptotene or beyond midpachytene. S1 nuclease digestion of mouse spermatocyte nuclei selectively released zygDNA, which hybridizes with lily zygRNA. zygRNA has not been detected in mouse somatic tissues. The profile of zygRNA formation and disappearance in mouse spermatocytes is very similar to that of zygRNA in lily meiocytes. PMID- 2580637 TI - Evidence that two mutations, wDZL and z1, affecting synapsis-dependent genetic behavior of white are transcriptional regulatory mutations. AB - Both the white mutant allele, wDZL, and the zeste mutant allele, z1, reduce white transcript levels in adult head tissues, but have no effect on these levels in other tested adult tissues. wDZL results from insertion of a complex transposon approximately 5.0 kb 5' to white. Juxtaposition of this transposon to white produces a novel transcription unit beginning in the transposon and producing a mature transcript containing both white and transposon sequences. Head-specific expression of this novel transcription unit correlates with the observed repression of wild-type white transcript levels. wDZL and z1 are known to cause synapsis-dependent repression of w+ expression in trans as assessed by eye pigment deposition. Collectively, these results suggest an unexpected and informative correspondence between cis and synapsis-dependent trans regulatory effects. We discuss the implied mechanistic relationship between regulation of transcription and transvection effects in Drosophila. PMID- 2580638 TI - Isolation and structure of a rhodopsin gene from D. melanogaster. AB - Using a novel method for detecting cross-homologous nucleic acid sequences we have isolated the gene coding for the major rhodopsin of Drosophila melanogaster and mapped it to chromosomal region 92B8-11. Comparison of cDNA and genomic DNA sequences indicates that the gene is divided into five exons. The amino acid sequence deduced from the nucleotide sequence is 373 residues long, and the polypeptide chain contains seven hydrophobic segments that appear to correspond to the seven transmembrane segments characteristic of other rhodopsins. Three regions of Drosophila rhodopsin are highly conserved with the corresponding domains of bovine rhodopsin, suggesting an important role for these polypeptide regions. PMID- 2580640 TI - Transcription termination within the E1A gene of adenovirus induced by insertion of the mouse beta-major globin terminator element. AB - In induced erythroleukemia cells, transcription of the beta-globin gene terminates in a region 600-1500 nucleotides downstream of the poly(A) site. To determine whether this region of the mouse DNA functions to terminate transcription when moved to another genomic site, portions of the putative termination region have been inserted into the E1A transcription unit of the adenovirus (type 5) chromosome. Analysis of RNA labeled either in isolated nuclei or in whole cells early after infection with reconstructed viruses indicated that transcription is terminated if the inserted DNA is oriented in the same direction as in the beta-globin transcription unit and contains the globin poly(A) site plus an additional 1395 nucleotides downstream. In addition to halting transcription within the E1A unit, the insertion of the terminator region had a negative cis effect on the E1B transcription unit, which normally initiates 363 bp downstream of the site of the globin insert. The E1B transcription unit was the only early gene affected, and complementation of the terminator virus with a wild-type E1A gene did not restore transcription of the E1B gene. PMID- 2580639 TI - Rearranged beta T cell receptor genes in a helper T cell clone specific for lysozyme: no correlation between V beta and MHC restriction. AB - The helper T cell clone 3H.25 is specific for hen egg white lysozyme and the class II MHC molecule I-Ab. This TH cell has three rearrangements in the beta chain gene family-a V beta-D beta-J beta 1 and a D beta 2-J beta 2 rearrangement on one homolog and a D beta 1-J beta 2 rearrangement on the other. These observations demonstrate that this functional T lymphocyte expresses only a single V beta gene segment and, accordingly, exhibits allelic exclusion of beta chain gene expression. The rearranged 3H.25 V beta gene segment is the same as that expressed in a T helper cell specific for cytochrome c and an I-Ek MHC molecule. Thus, there is no simple correlation between the V beta gene segment and antigen specificity or MHC restriction. PMID- 2580641 TI - RNA splicing in prokaryotes: bacteriophage T4 leads the way. PMID- 2580642 TI - Transcription termination and 3' processing: the end is in site! PMID- 2580643 TI - Antigenic variation is associated with DNA rearrangements in a relapsing fever Borrelia. AB - Borrelia hermsii, an agent of relapsing fever, undergoes antigenic variation in its host. Surface-exposed proteins with differing primary structures determine the serotype of each organism. Using amino acid sequence data from two of these variable proteins, we synthesized two mixed-sequence oligonucleotides and then used the oligonucleotides to probe mRNA and DNA of three isogenic serotypes of B. hermsii. In Northern blots the probes were specific for the mRNA of the homologous serotype. Southern blots revealed two classes of hybridizing fragments: those common to the three serotypes and those specific for a particular serotype. A serotype-specific DNA fragment, which had hybridized to both oligonucleotide probes, was cloned. Subsequent use of the cloned fragment as a probe provided further evidence that antigenic variation in B. hermsii is associated with DNA rearrangements and with occurrence of expression-linked copies of all, or part, of an antigen-specifying gene. PMID- 2580644 TI - [Instrumentation of the patch clamp technic for measuring individual ion channel currents in biological membranes]. PMID- 2580646 TI - [A paradox: deaf-muteness, a minor oral handicap]. AB - Deaf-muteness is a major handicap in the Occident because it brings on many disorders in the child's nerve plexus. On the contrary, in the societies with oral tradition, it seems that this handicap has no effect as far as attainments and functionings in the period of neurobiological and neurophysiological maturation are concerned. Current research suggests that orality circles produce very rich stimuli which develop perceptions and sensory abilities, in correlation with highly diversified abilities of the central nervous system. Moreover oral tradition develop a sign language within the comprehension of the child. Sensorial stimuli and sign language compensate for or remove the effects of deaf muteness during the neurological maturation and secure a normal harmonious development. PMID- 2580645 TI - [Therapeutic effect of huo xue-II injections on acute obliterative cerebrovascular diseases]. PMID- 2580647 TI - QSAR application in chemical carcinogenesis. II. QSAR analysis of a class of carcinogenesis inhibitor: retinoids. AB - Quantitative structure-activity relationships for the reversion of keratinization of hamster tracheal cell organ culture by structurally related retinoids were formulated. Their biological activities (ED50 . M) were correlated with the following parameters: the minimal topological difference (describing the fit of the considered molecules with a possible receptor site) and the lipophilicity constants. For computation purposes the retinoids were divided in three series (A, B and C) according to structural modifications in the cyclic moiety of the molecule, in the polienic chain and in the terminal functional group, respectively. The computed regression equations suggested the importance of the stereochemical features of cyclic moiety (for series A, eq. 1, n = 19, r = 0.926, F = 48.19) and of the uninterrupted conjugation for the polienic chain (for series B, eq. 6, n = 11, r = 0.954, F = 39.39) for the biological activity. In order to check the prediction potential of the regression equation computed for the overall set of compounds (eq. 10, n = 53, r = 0.853, F = 32.11), it was used to calculate the ED50 for a test series of 15 retinoids. The correlation obtained between ED50 exp and ED50 calc for this series was r = 0.916, F = 60.25. The nature of the receptor site possibly involved in the interaction with retinoids was discussed. PMID- 2580648 TI - The first stage and complete promoting activity of retinoic acid but not the analog RO-10-9359. AB - Retinoic acid has the ability to act as either a weak first stage promoter or a weak complete promoter in the initiation-promotion protocol for skin carcinogenesis in the SENCAR mouse. The retinoid analog RO-10-9359 lacks this tumor promoting activity. Both retinoids however inhibit 12-O tetradecanoylphorbol-13-acetate (TPA) promotion. Additional comparisons revealed that retinoic acid alone can induce dark keratinocytes, a characteristic of tumor promoters, while RO-10-9359 cannot. Retinoic acid but not RO-10-9359 can induce an immediate chemiluminescence response in human polymorphonuclear cells. Both retinoids, however, inhibit a TPA-induced response. Since the chemiluminescence response is believed to be due to oxygen free radical generation, the data suggest that the ability of retinoic acid but not RO-10-9359 to promote tumors and induce dark cells may be due to initial oxidative reactions at the cell membrane. PMID- 2580649 TI - Macroamylase immunoglobulins show high affinity for animal and human amylases. AB - We have examined the affinity shown by the immunoglobulin fraction from each of five sera containing macroamylase for amylases from different sources: human saliva or human, porcine, or ovine pancreas. High affinity constants, 0.4 X 10(10) to 7.2 X 10(10) L/mol, were found in competitive binding experiments with human or porcine pancreatic amylase. All but one serum yielded linear Scatchard plots, indicating that in most sera the amylase-binding immunoglobulins are homogeneous, possibly monoclonal. The immunoglobulin fractions from different sera differed in their specificity: two of them bound all four types of amylases, whereas two bound only one type. Three of the five immunoglobulin fractions showed considerably higher affinity towards one or both of the animal amylases than towards the human ones, and may be primarily directed against some animal amylase. PMID- 2580650 TI - The diagnosis of ectopic pregnancies in cases of lower abdominal pain using beta subunit assay of human chorionic gonadotropin. AB - The role of beta-subunit assay of human chorionic gonadotropin (hCG) in the early and accurate diagnosis and treatment of ectopic pregnancy was evaluated prospectively in a group of 57 women who presented with lower abdominal pains. A flow scheme for diagnosis work-up based primarily on hCG beta-subunit assay resulted in no false negative result. This enabled early and conservative treatment of the condition. Ectopic pregnancy was diagnosed early in more than one third of the patients. As a result conservative treatment was performed in cases were it was required and medically possible (33% of the cases). PMID- 2580651 TI - Ectopic pregnancy management by a non invasive protocol. AB - The hemodynamic stable patient suspected of extrauterine pregnancy may be a diagnostic challenge. Dilatations and curettage, Douglas puncture and laparoscopy are significant diagnostic aid in the investigation of the suspected ectopic pregnancy patient; but they are among the invasive methods. The introduction of non invasive methods such as serum beta subunit hCG and sophisticated ultrasound techniques seems to institute a more conservative approach to the "stable patient" prior to exposing her to anaesthetic and operative risks. A prospective study on "stable patients" suspected of "subacute" extrauterine pregnancy was undertaken in order to assess the diagnostic usefulness of a suggested non invasive protocol to determine whether its use has an advantage over the traditional invasive methods. 108 patients were evaluated in this study. 31 women were managed according to the non invasive protocol; patients presenting positive sonography signs underwent immediate operative procedure, patients in whom sonography revealed suggestive signs of E.U.P., expectant management was undertaken till serum beta subunit hCG confirmed or excluded the diagnosis. 77 patients were managed according to the invasive method protocol. Results indicate that the non invasive protocol has high diagnostic accuracy. Among the 31 patients no unnecessary intervention was performed. On the other hand, among the 77 patients, 43 laparoscopies were unnecessary. PMID- 2580652 TI - A new sensitive assay of human alpha-fetoprotein using time-resolved fluorescence and monoclonal antibodies. PMID- 2580653 TI - The visualization and characterization of two immunological forms of alpha 2 macroglobulin by immunoelectrophoretic methods. AB - Two peaks of alpha 2 macroglobulin (alpha 2M) were demonstrated in serum or plasma treated with trypsin using crossed immunoelectro-phoresis (CIEP). Both peaks moved the same distance in the first dimension and separated only when electrophoresed into antibody containing gel. The double peak phenomenon was shown not to be an artefact of the antiserum used and that the sample had to be fresh for both peaks to be visualised. Using the methods of staggered well CIEP and crossed thin layer gel chromatography (CTLGC) both peaks were shown to be of very similar antigenicity and molecular size. The technique of line immunoelectrophoresis (LIEP) demonstrated that the newly described lower peak was the alpha 2M/protease complex. The lowest concentration of alpha 2M/protease complexes that could be detected was 0.03 g/l. The two peaks of alpha 2M do not follow the theory of rocket immunoelectrophoresis (RIEP) and this is discussed. PMID- 2580654 TI - Prenatal diagnosis of trisomy 20 mosaicism indicating esophageal and rectal origin. AB - Trisomy 20 mosaicism in cultured amniotic fluid cells has in only a few cases been confirmed in fetal tissue. This may lead to the assumption that the trisomic cells are of extra-fetal origin and interruption of the pregnancy is not advisable. Chromosome analysis of numerous fetal tissues indicated in two cases the presence of one or more trisomy 20 cell clones in rectum and esophagus, respectively. The clinical significance of trisomy 20 mosaicism in single organs remains to be elucidated. Besides the karyotype, genetic counselling should take into account all accessible information of the pregnancy, e.g. ultra-sound, serum alpha-fetoprotein values and obstetrical history. PMID- 2580655 TI - Specificities and characteristics of mitochondrial protein antigens assessed by enzyme linked immunosorbent assay for anti-mitochondrial antibodies. Relationship to immunofluorescent and precipitating antibodies. AB - M-A, M-B and M-C are autoantibodies to mitochondrial proteins frequently found in primary biliary cirrhosis. To study the characteristics and specificities and to isolate antigens reacting with the autoantibodies a sensitive assay (ELISA) was established. Using this technique a significantly elevated level of antibodies was detected in patients with primary biliary cirrhosis (mean OD 460.2, s.d. 145.8) compared to normals (133.7 +/- 49.7). The assay correlated well with the indirect immunofluorescence test for detecting anti-mitochondrial antibodies and the mitochondrial fluorescence could be abolished by absorption of autoantibodies with the mitochondrial fraction. All three types of antibodies could be detected by ELISA; however, sera containing the combination of two or more antibodies yielded higher ELISA values. The ELISA confirmed that the M-A antigen is trypsin and acid (pH 3.0) sensitive but DNAase and RNAase resistant while the M-B antigen is DNAase and trypsin sensitive. The antigens were enriched in the supernatant isolated from the mitochondrial fraction centrifuged at 1,800 g for 60 min and 2% polyethylene glycol precipitates of the mitochondrial fraction. The antigens were found phosphate buffer soluble and therefore could also be enriched by phosphate buffer extraction of the mitochondrial proteins. Thus, ELISA described here provided a sensitive method in the assessment of characteristics and purification of autoantigens related to mitochondrial antibodies. PMID- 2580656 TI - Androgen receptor content of nafoxidine treated experimentally induced canine prostatic hyperplasia. AB - An estrogen stimulated increase in prostatic androgen receptor content has been postulated as the mechanism by which canine prostatic hyperplasia can be induced in the castrate dog treated with androstanediol and estradiol but not by androstanediol alone. In order to determine if the potent anti-estrogen Nafoxidine would inhibit this estrogen-associated development of prostatic hyperplasia, 2 week castrate young mongrel male dogs were injected for 1 month with either a) carrier solution (group 1), b) Nafoxidine (group 2), c) androstanediol and estradiol (group 3), or d) androstanediol and estradiol and Nafoxidine (group 4). At the termination of the experimental period the prostates of the animals in groups 1 and 2 were small (3.1 +/- 0.3 g (X +/- SEM) and 8.6 +/ 1.4 g respectively) and were atrophic histologically. The prostates in groups 3 and 4 were significantly heavier (24.7 +/- 3.0 g and 23.6 +/- 3.6 g respectively) than those in groups 1 and 2 and displayed glandular hyperplasia histologically. The dihydrotestosterone content of the prostatic tissue in groups 1 and 2 were similar (4.65 +/- 2.01 ng/mg DNA (X +/- SEM) and 3.13 +/- 0.65 ng/mg DNA respectively) and were significantly less than that of groups 3 and 4 (19.98 +/- 4.70 ng/mg DNA and 19.62 +/- 2.42 ng/mg DNA). The prostates of groups 3 and 4 thus displayed gravimetric, histologic and biochemical evidence of prostatic hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580657 TI - Abruptio placentae with coagulopathy: a rational basis for management. AB - Abruptio placentae rarely produces severe maternal complications while the fetus is alive in utero. The advent of fetal death (grade III) indicates a severe form of abruptio placentae and a real risk that an overt coagulopathy might develop (grade IIIB). Overt coagulopathy associated with a live fetus is, however, uncommon. The advent of an overt coagulopathy should be viewed as ominous. Treatment of abruptio placentae with overt coagulopathy should be directed toward obtaining a rapid and atraumatic vaginal delivery. Once delivery has occurred, spontaneous reversal of the coagulopathy can be anticipated. In the opinion of one of the authors (G.S.), the advent of severe consumption coagulopathy and/or uterine inertia is an indication for intravenous therapy with aprotinin. It has been shown that such therapy will limit DIC, reverse fibrinolysis, reawaken uterine activity, and lead to rapid vaginal delivery within 6-8 hours. Aprotinin is not commercially available for clinical use in the United States. Prolongation of the abruption-delivery interval will worsen maternal prognosis. Accordingly, the advent of uterine inertia prior to complete cervical dilatation is an indication for immediate cesarean section in circumstances where aprotinin is not available. Following delivery, the physician should be on the lookout for postpartum hemorrhage, which may necessitate immediate transfusion, the administration of oxytocics, and/or uterine manipulation. Surgical intervention is rarely indicated in such cases. The patient should also be carefully observed over the ensuing days and weeks for the evolution and resolution of complications, such as renal failure, pulmonary insufficiency, and panhypopituitarism. PMID- 2580658 TI - New approaches to treatment of squamous cell carcinoma of the vulva. PMID- 2580659 TI - Immunologic thrombocytopenic purpura. PMID- 2580660 TI - Carbonic anhydrase histochemistry. A potential diagnostic method for peripheral nerve repair. AB - Many large-diameter myelinated axons in spinal dorsal roots contain carbonic anhydrase activity, whereas few small-diameter ventral root axons stain for this enzyme. This differential localization of carbonic anhydrase in sensory and motor nerve fibers is indicative of the potential of carbonic anhydrase histochemistry to provide a convenient method for identifying predominantly motor or sensory fascicles in cut ends of peripheral nerves, thereby facilitating coaptation of fascicles in peripheral nerve repair. PMID- 2580662 TI - Trichotillomania--a review. PMID- 2580661 TI - Sudeck-type dystrophy in Paget's disease of bone. An anatomico-radiological approach. AB - Anatomico-radiological study of a humerus with Paget's disease and unhealed fracture makes it possible to demonstrate the uneven development of the disease according to local conditions. The possible role of a bone dystrophy similar to that in Sudeck's disease which might - along with a slow virus infection - be involved in the development of Paget's disease is discussed. The discussion is based on the present case, on two previous studies as well as on data found in the literature. PMID- 2580663 TI - Effect of gossypol on macromolecular synthesis in rat testis. An in vitro study. AB - Gossypol at a concentration of 10 micrograms/ml has been reported to be a specific inhibitor of DNA synthesis in mammalian cells in vitro. The present study investigates the in vitro effect of different concentrations of gossypol on rat testis tissue. In the presence of gossypol at a concentration of 10 micrograms/ml, DNA - as well as RNA - and protein synthesis were decreased to about 35% of the activity of controls. From these results it can be assumed that in rat testis tissue, gossypol acts as a more general inhibitor of macromolecular synthesis, an effect which may be at some common mechanism such as transport of precursors into the cells rather than a specific effect on the individual processes. PMID- 2580665 TI - Early physiologic changes in canine fecal peritonitis. AB - Oxygen delivery (DO2) and related variables were studied in eight dogs during severe untreated peritonitis induced by cecal ligation and perforation. The development of peritonitis was accompanied by abdominal fluid sequestration and significant increases in hemoglobin (Hgb), arterial oxygen content (CaO2), and P50. Changes in mixed venous PO2 (P-vO2), mixed venous saturation (S-vO2), DO2, oxygen uptake (VO2), cardiac index (CI), and arteriovenous O2 difference (C[a- v]O2) were not significant. When blood volume was returned to normal levels with dextran, CI rose and C(a--v)O2 decreased; P-vO2 increased and Hgb returned to baseline levels. In this animal model, sepsis and fluid sequestration produced an increase in blood O2 capacity and CaO2, which sustained DO2 and VO2. No changes were observed in P-vO2 or S-vO2. The hyperdynamic state of severe sepsis became evident only after reversing hemoconcentration by colloid infusion. The increase in P-vO2 and S-vO2 after volume loading is possibly related to primary septic mechanisms and/or to changes in DO2. PMID- 2580664 TI - Trials of serotonin, substance P and alpha 2-adrenergic receptor effects on the equine large colon. AB - Some support for both serotonin and substance P as biotransmitters in the equine large colon is presented. Close arterial injections of small quantities of each of these were effective, respectively, in stimulating marked increases in coordinated pressure peaks in the vicinity of the pelvic flexure, with modest (serotonin) or marked (substance P) increase in colon artery blood flow. Both the acaricide, amitraz, and the tranquilizer xylazine appeared to act on the equine large colon via yohimbine-sensitive alpha 2-adrenergic receptors. PMID- 2580666 TI - The shadow of life: psychosocial explanations for placenta rituals. AB - Culturally determined patterns of behavior associated with placenta disposal are characteristic of many modern and ancient societies. This paper defines this type of placenta disposal as a ritual event that delimits a "portion of reality"; explanations are provided leading to the conclusion that placenta rituals operate as anxiety releasing mechanisms that provide a means of control over the future health and welfare of mother, child, and community. The question of why the placenta figures so prominently in folk beliefs and practices has previously been attributed to its morphological and physiological properties; this paper argues that attributes associated with it from a psychosocial model are equally important. The data for this study were drawn from a compilation of ethnographic reports of post-partum practices in African, Asian, European, and Latin American societies. Additional information on placenta disposal was derived from interviews with 1,859 Peruvian informants. Analysis of the data obtained from the Peruvian studies show a significant difference between rural and semi-urban patterns of placenta disposal. PMID- 2580667 TI - A study of autoimmune allergic type I reactions in rheumatoid arthritis. IgE autoantibodies and histamine release from basophil leukocytes. PMID- 2580668 TI - Neurotransmitters in the brains of patients with dementia disorders. PMID- 2580669 TI - Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome (AIDS). Diagnosis with bronchial brushings, biopsy, and bronchoalveolar lavage. AB - Sixty-one diagnostic biopsies for Pneumocystis carinii pneumonia were performed on 40 homosexual male patients with acquired immunodeficiency syndrome (AIDS), using flexible fiberoptic bronchoscopy. Bronchial brushings and bronchoalveolar lavage were performed in conjunction with the biopsy in 58 and 29 bronchoscopies, respectively. Using a rapid methenamine silver stain, P carinii pneumonia was diagnosed in 27 (68 percent) of the patients. Twenty of these patients had a repeat biopsy one or more times for evaluation of therapy. Eighteen of the biopsies following two to three weeks of therapy were positive. There was an 84 percent correlation between findings on transbronchial brushing and biopsy (89 percent on initial biopsy before treatment) and an 86 percent correlation between bronchoalveolar lavage and biopsy. Additionally, transbronchial brushing permitted demonstration of Pneumocystis organisms in four follow-up bronchoscopies in which the biopsy was negative or inadequate. Rapid methenamine silver stain of transbronchial brushings permits diagnosis of P carinii pneumonia in patients with AIDS within one-half hour of bronchoscopy. PMID- 2580670 TI - The development of constraints on symbol-meaning structure in notation: evidence from production, interpretation, and forced-choice judgments. AB - Adults use notational systems in a variety of problem-solving situations. For notations to serve the goals we set them, they must conform to certain well formedness rules, including one-to-one mapping between symbols and meanings and maintenance of the same symbol-meaning relations for both encoding and decoding. Do young children show an appreciation for the utility of notation by adhering to these rules in their production, interpretation, and judgment of notations? Study 1 provides a descriptive analysis of notations created by children aged 5-11 years. Study 2 is a forced-choice task in which preschoolers, 6- and 7-year-olds, and adults chose between a notation that was well-formed according to Goodman's theory of notation and one that violated exactly one of Goodman's principles. The 2 studies present converging evidence that young children may not impose the same symbol-meaning structure at decoding that was set up at encoding, and only after this develops does a preference for one form-one function mapping appear (approximately age 8). Comparisons are made to relevant aspects of the literature on language acquisition. PMID- 2580671 TI - Application of the strange situation attachment paradigm to a neurologically impaired population. AB - Mother-infant attachment was studied in 24 mother/impaired infant dyads. The infants, from 12 to 26 months chronological age, manifested primary neurological impairment or undiagnosed delay in gross and fine motor development. Measures of general development and degree of child impairment significantly differentiated "classifiability" of attachment in the Ainsworth scheme; thus, the most severely impaired infants were rated "not classifiable." For those infants who were fully classifiable (80% of the sample), only 1 measure of general development or degree of impairment differentiated quality of attachment classification. Infants rated higher on a measure of social responsiveness were more likely to possess secure attachments than those receiving lower ratings on the measure. PMID- 2580672 TI - [Prognostically unfavorable factors in esophagus cancer. II. Value of diagnostic significance]. AB - The analysis of data of 121 patients with esophageal carcinoma treated at the Department of Surgery, Landeskrankenhaus Klagenfurt, between 1969 and 1982 revealed that neither histological type nor tumor grading had any significant influence on survival time (p = greater than 0,158). However, tumor localization and length influenced the chance of survival; the more proximal the tumor the poorer the chance to survive more than one year (p = 0,0008); patients with tumors less than 6 cm in length had a better chance of survival (p = 0,031). Cures were achieved only after resection for stage I. Resections for stage II and III did not show any difference in prognosis (p = 0,879). Although no cures could be achieved by surgery, the 1-year survival chance was increased threefold (p = 0,041). In the absence of contraindications, resection should be carried out even when mediastinal lymphnodes are involved by tumor. PMID- 2580673 TI - Silver staining of meiotic chromosomes in the fungus, Coprinus cinereus. AB - We have taken advantage of the synchronous meiotic process in the basidiomycete Coprinus cinereus to develop a simple and rapid method to selectively stain meiotic chromosomes and nucleoli in this fungus without prior removal of the cell wall. Electron microscopic examination of these silver-stained chromosomes indicated that the lateral elements of the synaptonemal complexes were prominently stained, and terminal attachment plaques were apparent. We found that a translocation quadrivalent could be recognized easily in the light microscope using these methods. The procedures appear suitable for the characterization of chromosome rearrangements in this small genome, and should facilitate cytogenetic analysis in this fungus. PMID- 2580674 TI - Three-dimensional distribution of Ag-NOR proteins in rat superior cervical ganglia nucleoli according to circadian rhythm. AB - A three-dimensional reconstruction of the distribution of Ag-NOR proteins in nucleoli of sympathetic neurons of a rat killed during the dark period of its light-dark cycle was compared with previously reported analyses on the three dimensional distribution of fibrillar centers, the high-resolution localization of these proteins, and the morphometric results. The domain occupied by these proteins appeared to far exceed that of the fibrillar centers and included the dense fibrillar RNP component. In the present material this component in turn provided partial bridging between the units consisting of the fibrillar centers plus their surrounding dense fibrillar component. PMID- 2580675 TI - [Advances in the chemotherapy of malignant lymphoma 1. Chemotherapy of Hodgkin's disease]. PMID- 2580676 TI - [Myxedematous heart disease--report of 11 cases including one autopsy]. PMID- 2580677 TI - [Effect of electroconvulsive shock on brain monoamines]. PMID- 2580678 TI - Effects of intravenous infusion of amino acids, fat, or glucose on unstimulated pancreatic secretion in healthy humans. AB - The effects of intravenous infusion of amino acids, fat, or glucose on unstimulated pancreatic secretion were studied in 31 healthy male volunteers. Each subject was studied twice on two separate days. On both days pancreatic outputs were measured during a 4-hr basal period that was followed by a 4-hr test period. During the test period either one of the digestive end products (100 ml/hr 10% amino acids in 13 subjects; 100 ml/hr 10% fat in 8 subjects; 150 ml/hr 10% glucose in 10 subjects) or saline was intravenously infused. The infusion of the digestive end products or saline on the two separate days was done in a randomized order. Six of the 10 subjects that had already been studied for glucose received a higher glucose dose (100 ml 20% glucose as a bolus followed by 300 ml/hr 10% glucose) in a third additional experiment. Intravenous infusion of amino acids significantly stimulated pancreatic outputs of trypsin and chymotrypsin, but left the outputs of amylase, lipase, bicarbonate, and volume unaffected. The low-glucose dose, as well as the fat infusion did not alter any of the pancreatic outputs. To analyze the relationships between different enzymes during the infusion of digestive end products, regression lines were calculated from the scatter of all individual pairs of enzyme measurements. Significantly different regression functions found for each condition (NaCl control, amino acids, fat, glucose) when trypsin and chymotrypsin were plotted versus lipase and amylase: amino acids shifted the function to a trypsin- and chymotrypsin-dominant pattern of secretion, glucose to an amylase-dominant pattern, and fat to a lipase dominant pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580679 TI - Intestinal infection with Mycobacterium avium in acquired immune deficiency syndrome (AIDS). Histological and clinical comparison with Whipple's disease. AB - At endoscopy, a 30-year-old man with acquired immune deficiency syndrome (AIDS), Kaposi's sarcoma, diarrhea, and unexplained malabsorption showed erythematous macular duodenal lesions consistent with Whipple's disease by histology and electron microscopy. Symptoms did not respond to tetracycline. Subsequent cultures revealed systemic Mycobacterium avium (M. avium) infection. Tissue from this patient, from patients with Whipple's disease and from a macaque with M. avium were compared. All contained PAS-positive macrophages but M. avium could be distinguished by positive acid-fast stains and a difference in pattern of indirect immunofluorescence staining with bacterial typing antisera. PAS-positive macrophages in the intestinal lamina propria are no longer pathognomonic of Whipple's disease. Ultrastructural and histological similarities between Whipple's disease and M. avium infection suggest that both are manifestations of immune deficits limiting macrophage destruction of particular bacteria after phagocytosis. M. avium must be considered in the differential diagnosis of diarrhea in patients with AIDS and other immunosuppressed conditions. PMID- 2580680 TI - [Effect of the stereochemistry of the alpha-terminal units of polyprenols on the capacity of their phosphates to participate in the biosynthesis of Salmonella O antigen. Research with synthetic and semisynthetic prenols]. PMID- 2580682 TI - [Phagemids in genetic engineering: an analysis of gene clonotheques]. PMID- 2580681 TI - [Functional compartmentalization of oxidative and glycolytic metabolism in frog skin]. PMID- 2580683 TI - [Barium currents through single calcium channels of a nerve cell membrane]. PMID- 2580685 TI - A study of the distribution pattern of lead in the leaves of banyan trees (Ficus benghalensis) from different traffic density regions of Calcutta. AB - The accumulation of lead from motor vehicle exhaust on leaves of banyan trees (Ficus benghalensis) growing on roadsides from different traffic density regions of Calcutta has been investigated and the values have been compared with a few samples from remote areas. The analysis has been performed during the summer (April-July) and winter (November-January) months to study the effect of seasonal variations, if any. The results indicate that in high and medium traffic regions, lead content of banyan leaves is high and is more prominent in winter months than in summer months. Such changes due to seasonal variations are not marked in low and zero traffic density regions. This preliminary investigation demonstrates a general indication of the distribution pattern of lead in plants exposed to motor vehicle exhaust along a relatively busy thoroughfare of the city of Calcutta. PMID- 2580686 TI - Studies on some biological differences between the chiral forms of methyl-1 naphthyl-p-nitrophenyl phosphorothionate. AB - A general degranulation test for carcinogens using the postmitochondrial supernatant (PMS) was based on the consistency of the stripping of ribosomes from rough endoplasmic reticulum. The degranulation phenomenon has been classified into three types, which are D1A, D1B and D11. This classification which is new has been introduced to probe more into the mechanistic aspects of degranulation. Aflatoxin B1 dimethylnitrosamine, 2-acetylaminofluorene, and 4 dimethylaminobenzene were carcinogens, evaluated in the PMS system. Reduced glutathione (GSH), oxidized glutathione (GSSG), sodium chloride, potassium chloride, lithium chloride, lithium carbonate, and ascorbic acid which are noncarcinogens and the (+) and (-) chiral forms of methyl-1-naphthyl-p nitrophenyl phosphorothionate were also evaluated in the PMS system. Lithium carbonate is teratogenic in rats. Similar findings have also been reported in mice, and lithium ion has been confirmed to be teratogenic in mice. This biological phenomenon of the D11 type could well evolve as a teratogenic effect and not a carcinogenic effect. PMID- 2580687 TI - Investigation of a test system for the rapid differentiation of nuclear and cytoplasmic damage in eucaryotes. AB - The effect of various agents which cause cell inactivation on the growth curves and RNA synthesis rates of yeast cells has been studied. On the basis of these investigations it was concluded that such studies can be used as a rapid test system for drawing preliminary conclusions as to whether a particular agent primarily damages the DNA of the cell nucleus or cytoplasmic structures. PMID- 2580688 TI - The use of the bivalve Mytilus edulis as a test organism for bioconcentration studies. I. Designing a continuous-flow system and its application to some organochlorine compounds. AB - Most bioconcentration studies have previously been carried out using fish as a test organism. Equally important is the use of bivalves for this purpose, from both an ecological and an economic point of view. A continuous-flow system has thus been designed for use also with extremely hydrophobic substances and evaluated using 2,4',5-trichlorobiphenyl, methoxychlor, pentachlorobenzene, and lindane. The variation of the uptake in the individuals after 3 weeks' exposure was quite small (relative standard errors varied from 10.1 to 15.3% depending on the test substance), indicating a high degree of reproducibility. The bivalves, however, are known to close their valves under unfavorable conditions, which occasionally may bias the results. To overcome this disadvantage, it is suggested that an internal standard--i.e., a chemically defined compound--be added to the water simultaneously with the test substances. Although there is a principal risk for interactive effects, unexpected variations in the uptake can thus be compensated for by relating the concentration of the test substance to the concentration of the internal standard in the organisms. Comparisons between continuous-flow systems and static systems have also been made. It is concluded that continuous-flow systems are more suitable for studying hydrophobic compounds than static systems. PMID- 2580689 TI - Computerized EEG pattern classification by adaptive segmentation and probability density function classification. Clinical evaluation. AB - A series of 63 clinical EEGs showing a variety of normal and abnormal patterns was analysed by computer with particular reference to the different types of pattern within the same EEG. Boundaries between different patterns were established by means of adaptive segmentation, so that the duration of the resulting segments was determined by the particular EEG itself (thus the term 'adaptive'). Four channels from each EEG were analysed, paired (left and right) channels were simultaneously segmented and analysed interactively. Similar segments were then clustered without supervision by estimating a probability density function in a 2-dimensional 'feature space' having dimensions of mean frequency and mean power. Individual clusters emerged as well-defined peaks of the surface, individual segments or small groups of duration insufficient to constitute a separate cluster, being identified as 'singular events' (e.g., rare sharp waves, artifacts). The autocorrelation function was used to characterize the EEG both for the segmentation and for the subsequent clustering of the resulting segments. In confirmation of our previous work, adaptive segmentation based on the autocorrelation function of the EEG was found to be quite satisfactory. Unsupervised clustering by estimation of the probability density function in feature space was found to give the correct number of clusters (usually less than 5) in a majority of the records (65%), but in the remaining minority of cases (35%), either overclustering or underclustering occurred. Further, the 'singular events' were occasionally partly included in a formal cluster. Comparison of these results of EEG clustering by unsupervised probability density function estimation with earlier results obtained by supervised hierarchical clustering suggests that there may be subtle cues used by the electroencephalographer in the classification of EEG patterns which have not been adequately approximated by the computer algorithms thus far used in this work. Hence at least some minimal degree of supervision in the clustering process may be necessary, at least for the present. On the other hand, the method recommends itself for the representation of illustrative EEG summaries which, in conjunction with a short written report, would provide the clinical neurologist with a sufficient picture of the real EEG without, in most cases, the need to inspect the original record. PMID- 2580690 TI - Age development and sex differences of various EEG elements in healthy children and adults--quantification by a computerized wave form recognition method. AB - The EEGs of 1416 healthy subjects aged 6-39 years were recorded and 1 min of background activity from Fp1, C3 and O1, was analyzed by a computerized wave form recognition method. Age development and sex differences of various EEG elements, which are employed in a conventional clinical EEG assessment, were statistically analyzed. The age developments of alpha and theta showed regional differences and were the most rapid in O1 and the slowest in C3. The delta amplitude, theta amplitude, theta continuity and percentage time of theta with an amplitude of 30 microV or more, which are important in a clinical EEG assessment, reached a stable level at 18-21 years of age in the 3 leads. The percentage time, amplitude and continuity of alpha in the 3 leads reached a stable level at 22-25 years of age. Including the low voltage theta in Fp1 and C3, all of the EEG elements reached the stable adult level at 26-29 years of age. Since there was a large interindividual variability in these age developments, the regression curves of the 10th and 90th percentiles of these EEG elements can be considered as quantitative standards for clinical EEG evaluation. As for sex differences, the percentage alpha time and alpha continuity were greater in males than in females after adolescence. The percentage theta time in Fp1 and C3 was greater in females than in males during childhood. The percentage beta time was higher in females than in males at all ages. But overall, these sex differences were minor compared with the differences associated with age developments of the EEG elements. PMID- 2580691 TI - Medium- and long-latency responses to displacements of the ankle joint in patients with spinal and central lesions. AB - In order to elucidate further the possible pathways and the functional significance of long-loop reflexes we recorded short-, medium- and long-latency responses from leg muscles in 27 patients with spinal lesions, 20 patients with central lesions of the internal capsule or cerebral hemisphere, and in 18 control patients with frontal or occipital lesions without motor or sensory disturbances. Our normal population included 50 subjects, who were age and sex matched to the patients. The mean latency of the long-latency response (LL) in the anterior tibial muscle was significantly delayed in patients with spinal (164.5 msec) and central lesions (145.1 msec) compared to control patients (123.5 msec) and the normals (125.3 msec). This delay of LL could be observed in patients who exhibited only motor or sensory disturbances or a combination of both. The medium latency response (ML) was absent in 47% of the records in patients with spinal lesions, mainly on the side which was clinically more affected. Its latency was normal if the response occurred. The integral of the LL response was enlarged in patients with spinal or central lesions, but was also enlarged in the control group. The results indicate that the ML response is segmental, but that its amplitude is modulated by supraspinal structures. The LL response probably corresponds to a transcortical 'reflex.' PMID- 2580692 TI - Recovery from alpha coma after decompression sickness complicated by spinal cord lesions at cervical and midthoracic levels. AB - A modified alpha pattern activity occurred in the EEG of a 21-year-old man during recovery from a diving injury. It persisted for 10 days but finally the EEG became normal. There was clinical and neurophysiological evidence of additional separate lesions in the cervical and mid-thoracic spinal cord. The latter resulted in spastic paraplegia but the patient made an otherwise good recovery. PMID- 2580684 TI - Clinical application of inhibitors of fibrinolysis. AB - The basic proteinase inhibitor from bovine organs, aprotinin, was first identified in 1930 and its effect on enzyme and other biological systems has since been extensively studied. Aprotinin can only be administered intravenously and has a half-life of about 2 hours. Its administration at the start of cardiopulmonary bypass surgery appears to reduce blood loss and to protect against global myocardial ischaemia. Similarly, a smaller infarct size seems to result from early administration of aprotinin within the first hour after myocardial infarction, though further studies are needed to confirm this effect. A combination of aprotinin with tranexamic acid may be effective in preventing or delaying rebleeding after rupture of an intracerebral aneurysm; the addition of aprotinin seems to decrease the incidence of delayed cerebral vasospasm and ischaemic complications which are sometimes noted when tranexamic acid alone is used. Aprotinin is also effective as adjuvant treatment in traumatic haemorrhagic shock. The recommended loading dose is 15,000 to 20,000 KIU/kg bodyweight administered as a short intravenous infusion, followed by 50,000 KIU/hour by continuous infusion. Side effects of aprotinin are very rare. Epsilon Aminocaproic acid (EACA), p-aminomethylbenzoic acid (PAMBA) and tranexamic acid are synthetic antifibrinolytic amino acids. Saturation of the lysine binding sites of plasminogen with these inhibitors displaces plasminogen from the fibrin surface. On a molar basis tranexamic acid is at least 7 times more potent that epsilon-aminocaproic acid and twice as potent as p-aminomethylbenzoic acid. All 3 compounds are readily absorbed from the gastrointestinal tract and excreted in active form in the urine. The plasma half-life of tranexamic acid is about 80 minutes. The main indications for tranexamic acid are the prevention of excessive bleeding after tonsillectomy, prostatic surgery, and cervical conisation, and primary and IUD-induced menorrhagia. It is possible that gastric and intestinal bleeding can also be reduced as well as recurrent epistaxis. Tranexamic acid could also be useful after ocular trauma. The value of fibrinolysis inhibitors in the prevention of bleeding after tooth extraction in patients with haemophilia is well documented, as is the treatment of hereditary angioneurotic oedema. The usual dose of tranexamic acid is 0.5 to 1g (10 to 15 mg/kg bodyweight) given intravenously 2 to 3 times daily, or 1 to 1.5 g orally 3 to 4 times daily. This dose needs to be reduced in patients with renal insufficiency. The main side effects of tranexamic acid are nausea or diarrhoea. PMID- 2580693 TI - Ambulatory sleep-wake polygraphy in narcolepsy. AB - We have presented an ambulatory monitoring and off-line data analysis system for sleep-wake polygraphy and have illustrated its use for the diagnosis of narcolepsy. The advantages over conventional polysomnography have been discussed. PMID- 2580695 TI - A surface electrode array for detecting action potential trains of single motor units. AB - Action potentials of single motor units were detected by a linear surface electrode array placed perpendicular to the longitudinal axis of the biceps brachii. Twelve myoelectric signals were derived simultaneously from a voluntarily contracting muscle. Using a visual feedback control, 3 subjects produced spike trains of single motor unit action potentials (MUAPs) at a weak contraction. When the myoelectric signals showed an interference pattern at a moderate contraction, several MUAPs were isolated by a visual analysis. MUAPs occurring at about fixed intervals with constant amplitudes and with identical wave forms were presumed to be the action potential trains of single motor units. Reliable estimates of single MUAP wave forms were obtained by averaging and superimposing the detected signals at a timing of characteristic potential peaks. Then not only the firing rate of the spikes but also the territory and the wave form of single MUAPs were investigated. Most MUAPs had a sharp and symmetrical distribution of potentials on a skin surface along the muscle circumference, while some MUAPs showed complex wave forms with some separate potential peaks. The possible arrangement of muscle fibers belonging to the motor units was estimated from the MUAP wave forms. PMID- 2580694 TI - ERPs to response production and inhibition. AB - Three experiments investigating the effects of response production and inhibition on the N2 and P3 components of the ERP are reported. In the first experiment, 12 young female volunteers were presented with the words "push' and "wait' (semantic stimuli). On a separate series of trials, they were presented with arbitrary symbols assigned the same meanings (symbolic stimuli). For each stimulus series half of the stimuli were degraded. To obtain an estimate of reliability of the data, each task was repeated. Data were collected from Fz, Cz and Pz electrode sites. The P3 amplitude had a parietal maximum when the stimuli instructed subjects to respond (Go). The P3 was equal at central and parietal sites when the stimuli instructed the subjects to withhold a response (No-Go). This topographic pattern was obtained for all stimulus manipulations, simple and degraded stimuli, words and symbols, and for the first and second runs. The N2 was a frontal maximum component that was larger to the No-Go than to the Go stimuli. This result was also robust to the manipulations. A second experiment investigated the dependency of these findings on an overt motor response. In this experiment, the symbolic and semantic stimulus series were each presented twice. The subjects counted the Go stimuli and did not count the No-Go stimuli for one presentation and pressed the reaction time button as in experiment 1 for the other presentation. While counting (compared to button pressing) delayed the N2 and P3 peaks, counting and pressing produced similar results, including the Go/No-Go P3 distribution effects. A third experiment investigated the sensitivity of these findings to the orientation of the symbols instructing the subjects to respond or withhold the response. Again the pattern of results was robust to this manipulation. PMID- 2580696 TI - A non-linear analysis of afferent modulatory activity in the cat somatosensory system. AB - The effects of prior input on afferent activity in the somatosensory system of the cat have been studied using both twin-pulse experiments and random stimulus trains for which evoked activity is characterized by a set of mathematical functions known as kernels. The kernels quantitatively characterize transformational processes occurring in the system. The first-order kernel is analogous to a classical averaged evoked potential, but to temporally interacting stimuli; the second-order kernel may be likened to a generalized recovery function. Responses to superficial radial nerve stimulation were obtained at sensory (S1) cortex, thalamic n. ventralis posterolateralis (VPL), and the nucleus cuneatus of the dorsal column nuclei (DCN). Comparison of first-order kernels with averaged evoked potentials showed good agreement in chronic awake, chronic anesthetized, and acute anesthetized animals. Second-order kernels indicated complex interactions with an overall depression of subsequent response amplitudes. Comparison between second-order kernels and the results of the two pulse experiments at both S1 cortex and VPL showed good agreement for early latency response components, but significant deviations for later components suggest higher than second-order non-linearities for this system. PMID- 2580697 TI - Removal of ocular artifacts from the EEG--a biophysical approach to the EOG. AB - The present paper describes the propagation of ocular potentials across the scalp on a biophysical basis. It is concluded that 3 EOG derivations (two for EEG records along the midline) are generally necessary to account for ocular disturbances in the EEG. The inadequacy of many methods suggested for EOG artifact control may be due to the false assumption that just one EOG derivation provides enough information to remove ocular potentials from any EEG recording along the mid(-sagittal) line. A comparison of compensation with one or with two EOG derivations is described for a data set of slow brain potentials. A frequency dependence of the ocular influence cannot be neglected, if fast and slow EOG activities have to be removed. The present considerations should allow a more theoretically based decision of the EOG correction method necessary for a certain data set. PMID- 2580698 TI - Phase synchronized triggering: a method for coherent noise elimination in evoked potential recording. AB - While standard evoked potential recording techniques reliably attenuate gaussian and white noise, they are not similarly effective in reducing coherent noise such as that induced by power lines. We have presented a technique that will effectively eliminate coherent noise. This technique is especially appealing for clinical settings where 60 Hz artifact and a few discrete frequencies are most troublesome, such as in operating rooms or intensive care units. An added advantage of the technique is that it is especially well suited to applications requiring small sample sizes. PMID- 2580700 TI - A molecular model for ion selectivity in membrane channels. AB - In this article, the three-dimensional motion of an ion within a molecular channel is discussed for the first time; escape rates from binding sites are calculated using the transition state method. For a given ligand configuration and a particular pore radius the rates depend upon ion size and mass. It is found that the activation energies depend strongly on the ion size, i.e., they increase with decreasing ion radius. In contrast to the rates obtained from the mass dependence alone, the rates depending on both mass and size of the alkali ions yield the completely inverted sequence, namely the Eisenman sequence I. PMID- 2580699 TI - A model for the resistance of the proton channel formed by the proteolipid of ATPase. AB - The conductance observed for single proton channels formed by proteolipids of ATPase (Schindler and Nelson 1982) is rationalized in terms of a hydrogen bonded network model. A simple algebraic expression for the resistance predicted for such a model is presented and the results are compared to the experimental observations. The comparison suggests that the conduction involves a series of bound water molecules and perhaps amino acid side groups. PMID- 2580701 TI - Non-equilibrium voltage noise generated by ion transport through pores. AB - In this paper, we describe a systematic approach to the theoretical analysis of non-equilibrium voltage noise that arises from ions moving through pores in membranes. We assume that an ion must cross one or two barriers in the pore in order to move from one side of the membrane to the other. In our analysis, we consider the following factors: a) surface charge as a variable in the kinetic equations, b) linearization of the kinetic equations, c) master equation approach to fluctuations. To analyze the voltage noise arising from ion movement through a two barrier (i.e., one binding site) pore, we included the effects of ions in the channel's interior on the voltage noise. The current clamp is considered as a white noise generating additional noise in the system. In contrast to what is found for current noise, at low frequencies the voltage noise intensity is reduced by increasing voltage across the membrane. With this approach, we demonstrate explicitly for the examples treated that, apart from additional noise generated by the current clamp, the non-equilibrium voltage fluctuations can be related to the current fluctuations by the complex admittance. PMID- 2580702 TI - Single voltage-dependent and outward rectifying K+-channels in isolated rat heart cells. AB - Studies on single K+-channel currents recorded from isolated rat heart muscle cells, in which early repolarization is known to be exceptionally fast, are reported here. A K+-channel which is blocked by TEA (tetraethylammonium) from the inside only has been found. The total open time of the channel, measured in steady-state after activation, indicated outward rectifying properties. The single channel conductance increases with depolarization from 25 pS at -70 mV to 75 pS at + 70 mV. Selectivity of the channel has also been measured and it was found that only Rb+ and K+ can permeate the channel, whereas the permeability (P) for Li+, Na+, Cl-, Mg2+, and Ca2+ is less than 0.05 times PK+. Ba2+ and CS+ block the channel activity. These results clearly demonstrate the existence of K+ selective outward rectifying conductance pathways in rat ventricular myocytes. PMID- 2580703 TI - Measurement of IgG in equine blood by immunoturbidimetry and latex agglutination. AB - This paper describes the quantitative measurement of IgG concentrations in equine blood/serum by turbidimetric analysis and the qualitative assessment using latex agglutination. The concentration of IgG in foal serum measured by turbidimetry correlated well with the results obtained by radial immunodiffusion (r = 0.91) and the gamma-globulins estimated from the electrophoresis of serum on cellulose acetate (r = 0.92). The method, using antibody-coated latex beads, to detect foals with serum IgG concentrations of less than 4 g/litre (whole blood less than 2 g/litre) proved to be accurate in 96 per cent of cases and provided a quick and simple qualitative test, suitable for use outside the laboratory. PMID- 2580704 TI - Detection of human rotavirus by nucleic acid analysis in comparison to enzyme linked immunoassay and electron microscopy. AB - The results of RNA analysis for the detection of rotavirus were compared with those of a standard enzyme-linked immunosorbent assay (ELISA) and electron microscopy using 212 faecal specimens obtained from 200 children with gastroenteritis. Rotavirus was extracted directly from faecal specimens and RNA segments were made visible by polyacrylamide gel electrophoresis using a silver staining technique. Of the 212 faecal specimens 137 were found to be positive in ELISA, 125 in RNA analysis and 121 in both methods. Forty-nine of the 212 specimens were also investigated by electron microscopy. Thirty-five were positive when examined by electron microscopy, 37 were positive in ELISA and 33 in RNA analysis. RNA analysis of 119 faecal samples in outbreaks and sporadic cases of rotavirus infection yielded 42 different rotavirus electrophoretypes. The results indicated that no one method was sufficient to detect all positive specimens and that RNA analysis is useful in epidemiological studies. PMID- 2580706 TI - Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens. AB - Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. The latter fraction strongly expressed the oncofoetal antigens recognised by natural antibodies in mouse sera and the hybridoma antibody FC 10.2, and this activity was enhanced after mild acid hydrolysis to remove sialic acid and fucose residues. Oligosaccharides were released from the mild-acid treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. Their structures, in order of abundance, were: (Formula: see text). PMID- 2580705 TI - Characterization of transcriptionally active DNA-protein complexes from chloroplasts and etioplasts of mustard (Sinapis alba L.). AB - DNA-protein complexes that are capable of RNA synthesis in vitro (transcriptionally active chromosomes) were isolated from both chloroplasts and etioplasts of mustard (Sinapis alba L.) seedlings. Analyses of the polypeptide pattern of these complexes indicate that they comprise a specific subset of plastid proteins, distinct from the overall pattern of either the soluble or membrane-bound plastic proteins. DNA-protein complexes from the two plastid types have polypeptides in common. However, at least several polypeptides are highly enriched in either the chloroplast or the etioplast DNA-protein complex. The EcoRI restriction endonuclease fragments of the DNA associated with the complexes from either plastid type are the same. They are identical with the fragments obtained from highly purified chloroplast DNA. The transcriptional activity of the chloroplast complex is more than ten times higher than the activity of the etioplast complex. However, the complexes from either plastid type are capable of transcribing DNA regions containing genes for both the plastid rRNAs and for plastid proteins. In vitro transcripts were found to hybridize not only to DNA regions for mature in vivo RNA but also to adjacent regions, indicating synthesis of precursor RNA sequences by the transcriptionally active chromosomes. PMID- 2580707 TI - Spermidine level as a parameter in the treatment of patients with malignant melanoma. AB - Before, during, and after 19 courses of chemotherapy given to patients with disseminated malignant melanoma plasma spermidine levels were determined with a radioimmunoassay. Baseline values were normal in 17 courses, a doubling of plasma levels following chemotherapy occurred in 13 courses. There was no relation between the occurrence of a tumor response and an increase in spermidine levels nor between hematological toxicity or digestive tract toxicity and spermidine levels. PMID- 2580709 TI - Developmental and behavioural disturbances in 13 boys with fragile X syndrome. AB - Developmental and behavioural aspects were studied in 13 boys aged 2.6-12.5 years from three families with the fragile X syndrome. The following observations were made. Moderate to severe retardation was present in all boys; non-verbal IQs ranged between 25 and 67 (mean 46 +/- 14); IQ and age were negatively correlated (P less than 0.01). Language development was grossly delayed in all boys; most had severe articulation problems. Imitative and symbolic play (e.g. doll play) were strikingly retarded as compared to abstract play (e.g. block design). Autistic features such as no use of eye contact, stereotyped movements and echolalia were found in 9/13 boys; the same number showed aggressive behaviour. General activity was reduced during the 1st year of life; most boys became very hyperactive during the second year; and short attention span and increased distractability were observed in all. Motor development was mildly delayed; all boys were clumsy and moderately hypotonic. The fragile X syndrome ought to be considered in retarded boys with a dissociated developmental pattern, in particular a striking delay in language and play development, and autistic features. PMID- 2580708 TI - Etretinate therapy in children with severe keratinization defects. AB - Keratinization defects can be very severe and disfiguring diseases. The development of retinoids such as etretinate has provided us with an effective symptomatic form of oral therapy for these skin conditions. Based on our own experience, we briefly outline the therapeutic potential of etretinate in various keratinization defects (lamellar ichthyosis, Netherton syndrome, Sjogren-Larsson syndrome, mal de Meleda and juvenile pityriasis rubra pilaris). The toxicology of etretinate is reviewed with special regard to the treatment of children. Bone changes such as premature closure of the growth line or other unacceptable side effects have so far not been observed. Guidelines for patient selection and for the safe treatment of children are given. PMID- 2580710 TI - 3-Methylglutaconic and 3-methylglutaric aciduria in a patient with suspected 3 methylglutaconyl-CoA hydratase deficiency. AB - A girl suffering from marked muscular hypotonia, severe statomotor and mental retardation, bilateral optic atrophy with chorioretinal degeneration, convulsions and a moderate compensated metabolic acidosis is described. Screening for metabolic disorders revealed massive 3-methylglutaconic with 3-methylglutaric aciduria leading to the tentative diagnosis of 3-methylglutaconyl-CoA hydratase deficiency. Metabolite excretion was correlated with variation of leucine intake. 3-methyl-3-hydroxyglutaryl-CoA lyase activity in cultured fibroblasts was normal. The suspected metabolic defect was not demonstrable in cultured skin fibroblasts, however. PMID- 2580711 TI - Immunohistochemical demonstration of tumor-associated antigens in prostatic carcinomas of various histological differentiations. AB - Prostate acid phosphatase (PAP), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA) and keratin were determined immunohistochemically in paraffin sections from 64 prostatic carcinomas fixed in formalin according to the conventional method. The results obtained with PSA led to the correct diagnosis of prostatic carcinoma in 90.7% of the cases. 80.3% of the diagnoses obtained with PAP were correct. The intensity of the staining of the marker decreased with increasing differentiation. 3 utricular carcinomas were positive for PAP and PSA. CEA and keratin may be considered unspecific tumor markers only. However, metaplastic squamous epithelium from poorly differentiated carcinomas was always positive for keratin. PAP and PSA are also suitable for differentiating between tumors of prostatic and nonprostatic origin and could thus be successfully used to determine immunohistochemically the histogenesis of 15 invasive, poorly differentiated carcinomas of the prostate and bladder. PSA again proved to be a more specific epithelial marker than PAP. PMID- 2580712 TI - Acute effects of antiarrhythmic drugs on stable ventricular premature beats. Controlled comparison of lorcainide and lidocaine. AB - Nineteen patients with refractory but stable ventricular premature beats (VPB) received 3 medications intravenously at 24-h intervals. Lorcainide (2 mg/kg) and placebo were given double-blind in randomized sequence and the third treatment was 100 mg lidocaine, the standard reference drug. Continuous ECG recordings were made for the first 2 hours after administration to study the antiarrhythmic effect; the stability of the arrhythmia, the absence of residual and of period effects, and the interdrug differences in efficacy were statistically evaluated. Lorcainide significantly reduced the frequency of VPB during the 2-hour period, whereas the effect of lidocaine was more short-lived. The median individual peak reduction in VPB was 96% for lorcainide and 47% for lidocaine. No significant reduction in VPB was observed with placebo. Adverse effects were acceptable with either active treatment. PMID- 2580714 TI - Autoantibodies to anti-DNA with anti-allotypic and anti-idiotypic specificities in (NZB X NZW)F1 mice. AB - The monoclonal A52 (IgG2b, kappa) anti-DNA autoantibody represents a major cross reactive idiotype in the murine and human autoimmune response to DNA. Examination of sera and purified IgG derived from (NZB X NZW)F1 mice showed that these mice develop an age-dependent binding reactivity with the pure anti-DNA IgG. Three monoclonal antibodies possessing this reactivity were prepared from unprimed female (NZB X NZW)F1 mice. One of these monoclonal antibodies appeared to be directed against allotypic determinants present in the NZB IgG2b; the other two antibodies exhibited a marked preference for idiotypic determinants of the A52 IgG. The IgG anti-allotype and anti-idiotype activities in (NZB X NZW)F1 mice may, therefore, represent the products of a deregulated immune system and/or constitute the normal elements of a functional immune regulation system. PMID- 2580713 TI - Constraints in T-B cooperation related to epitope topology on E. coli beta galactosidase. I. The fine specificity of T cells dictates the fine specificity of antibodies directed to conformation-dependent determinants. AB - Experiments to test the relationship between the epitopes on a protein antigen recognized by T and B cells in their collaboration to produce antibody cannot rely solely on hapten-carrier models. In the present work we used E. coli beta galactosidase, a molecule whose tertiary and quaternary epitopes have been well characterized, as the model antigen. T helper cells were raised by stimulating mice with the intact or the denatured molecule or with any of several beta galactosidase cyanogen bromide peptides. In a series of in vitro helper T cell assays we confronted the various T populations with B cells preimmunized with the native antigen, and we tested their capacity to help production of (a) binding antibodies and (b) antibodies directed to single conformational epitopes, characterized by their capacity to protect the enzyme from heat denaturation or to activate defective beta-galactosidase. According to our results, (a) equivalent T cell help can be provided by T helper cells primed with native or denatured antigen, even for the production of "conformational" antibodies; (b) one of the peptides (CB-18) is most efficient in raising help for binding antibodies; and (c) two peptides (CB-20 and CB-21) rank highest in priming T helper cells for the eventual production of protecting and activating antibodies, respectively. Thus, not every beta-galactosidase-specific T helper cell is useful in providing help to B cells specific for any particular epitope on the molecule, but rather preferential pairings exist, possibly governed by a proximity rule. PMID- 2580715 TI - Alloreactive cytotoxic T cells. I. Alloreactive and allorestricted cytotoxic T cells. AB - Nylon wool-nonadherent spleen cells from three inbred mouse strains of H-2k (CBA), H-2d (BALB/c) and H-2b (C57BL/6) haplotype were co-cultured with 2,4,6 trinitrophenyl (TNP)-modified or nonmodified allogeneic stimulator cells in a limiting dilution system. Using a recently described restimulation protocol, a surprisingly large number of splenic cytotoxic lymphocyte precursors (CLP) was clonally expanded in this primary in vitro response to allo-H-2 plus TNP determinants; measured CLP frequencies ranged from 1/30 to 1/300. The lytic specificity patterns of individual microcultures (selected for a high probability of clonality) were defined by split well analysis, and were furthermore followed up in time by sequentially reassaying microcultures at different time points of in vitro incubation. This analysis revealed the following: a large fraction of cytotoxic T lymphocyte clones lysed TNP-modified but not nonmodified allogeneic concanavalin A blast targets, i.e., were allorestricted; this was found in all 6 allogeneic strain combinations set up with b, k and d haplotype mice; allorestricted lytic patterns predominated in microcultures with low numbers of responder cells per well, and at late time points of in vitro culture; allorestricted lytic cultures were specific for the stimulating allogeneic H-2 plus TNP determinant(s); and allorestricted lytic patterns were also found in microcultures stimulated by nonmodified allogeneic cells. To our knowledge, these are the highest CLP frequencies yet reported in limiting dilution systems that used a specific (re)stimulation protocol and measured the lytic responses obtained in a specificity-controlled readout. PMID- 2580716 TI - Antibody-mediated suppression of the immune response is determinant specific. AB - It was studied whether antibody-mediated suppression of the immune response was determinant specific. Fluorescein isothiocyanate (FITC)-conjugated sheep red cells were used as the immunogen and antibodies were raised both against the carrier sheep red cells and the hapten FITC. When these antibodies were injected 1-3 h after the immunogen they only suppressed the immune response to the corresponding determinant. Anti-carrier antibodies usually enhanced the response to the hapten. Therefore, antibody-mediated suppression of the immune response is determinant specific and cannot be mediated in vivo to a detectable extent by the Fc part of the antibodies. PMID- 2580717 TI - Pupillary supersensitivity to substance P following prolonged treatment with tetrodotoxin or substance P antagonists. AB - Pilocarpine contracts the sphincter pupillae muscle via an effect on muscarinic receptors and phenylephrine contracts the dilator pupillae muscle via an effect on alpha-adrenergic receptors. These effects are thought to mimic the action of the parasympathetic and sympathetic nervous systems, respectively. Intracellular injection of substance P (SP) produces an atropine-resistant constriction of the pupil. This response is thought to mimic the effect of local sensory reflexes on the sphincter pupillae muscle, involving SP-containing trigeminal nerve endings. Repeated intraocular injections of tetrodotoxin, a general blocker of nervous conduction, over a period of 3 weeks produced supersensitivity to pilocarpine, phenylephrine and SP in the rabbit iris. These findings support the view that, like acetylcholine and noradrenaline, SP or an SP-like compound acts as a neurotransmitter in the iris. Also, long-term topical application of an SP antagonist, (D-Pro2,D-Trp7,9)-SP or (Arg5,D-Trp7,9)-SP5-11, to the rabbit eye produced supersensitivity to SP but not to pilocarpine, thus supporting the view that the SP antagonists interact specifically with the SP receptors. The isolated rabbit iris sphincter muscle responds to electrical stimulation with a cholinergic twitch followed by a slow non-cholinergic contraction that can be blocked by antagonists to SP. Analysis of the motor activity of the iris sphincter muscle after long-term topical treatment of the eye with an SP antagonist followed by an interval of 2 days after termination of treatment revealed a greatly enhanced non-cholinergic contraction compared with the cholinergic twitch, a finding that seems to be consistent with the idea that supersensitivity to SP had developed. PMID- 2580718 TI - Co-existence of substance P and calcitonin gene-related peptide-like immunoreactivities in sensory nerves in relation to cardiovascular and bronchoconstrictor effects of capsaicin. AB - Immunohistochemical studies showed that substance P (SP) and calcitonin gene related peptide (CGRP) immunoreactivity co-exist in capsaicin-sensitive primary sensory neurons. Varicose SP- and CGRP-immunoreactive nerve fibres with a similar distribution pattern were seen in the lower airways and heart. The functional analysis revealed that CGRP caused cardiac stimulation and had, together with SP and neurokinin A, potent hypotensive effects. Vascular permeability was increased by SP and neurokinin A, and the bronchial smooth muscle was particularly sensitive to neurokinin A. Thus, multiple peptides stored in an possible released from the same nerve endings by capsaicin may exert differential effects in various target tissues. PMID- 2580719 TI - Interaction of tachykinins with an adrenergic receptor in the rat urinary bladder. AB - The rat urinary bladder was examined as a model for studying tachykinin receptors. The order of potency, the maximal effect and the slope of the dose response curve were examined with six tachykinins - substance P (SP), physalaemin, phyllomedusin, uperolein, eledoisin, kassinin - and several substance P fragments - SP-(2-11), SP-(3-11), SP-(4-11) and SP-(6-11). The tachykinin receptor on the rat urinary bladder was shown to bind preferentially tachykinins having a hydrophilic amino acid residue in position 5-6, as occurs with physalaemin, phyllomedusin, eledoisin and kassinin. The N-terminal of the tachykinins and in particular substance P is suggested to play a major role in regulating affinity, intrinsic activity and the slope of the dose-response curve. The tachykinins are thought to exert a direct action on smooth muscle. An accessory binding site associated with the tachykinin receptor on rat urinary bladder was also identified. This accessory site binds the N-terminal amino acids of the tachykinins as well as some alpha-adrenergic compounds (phentolamine, prazosin, noradrenaline or adrenaline in the presence of propranolol). When the accessory binding site is occupied by adrenergic compounds, the affinity of the tachykinins is markedly reduced. This observation is interpreted to mean that catecholamines may have a modulatory influence on tachykinin activity on the rat urinary bladder. PMID- 2580720 TI - Agents that increase cellular cyclic AMP or calcium stimulate prolactin release from the 235-1 pituitary cell line. AB - The 235-1 pituitary tumor clone was utilized to study prolactin secretion after perturbing cyclic AMP and calcium metabolism. Cellular cyclic AMP levels were elevated after treatment with PGE1, cholera toxin, forskolin, isobutylmethylxanthine as well as dibutryl cyclic AMP; these cyclic AMP responses were associated with increased prolactin release. Ionophore A23187 and maitotoxin, which enhance calcium uptake into cells, also amplified prolactin secretion. In contrast, the calmodulin antagonists penfluridol and W7 reduced basal prolactin release. These data support the hypothesis that cyclic AMP, calcium and calmodulin can participate in prolactin release from 235-1 cells. PMID- 2580721 TI - Differences in dopamine- and noradrenaline-induced amylase release from the rat parotid gland. AB - The effects of dopamine and noradrenaline on amylase secretion from rat parotid gland were studied in a batch incubation system. Dopamine effectively caused amylase secretion but the concentration-response curve was shifted to the right in reserpinized animals, suggesting a minor indirect component in the action of dopamine. The noradrenaline-evoked secretion was the same in reserpinized glands as in the controls. Bromocriptine, a dopamine receptor agonist, was without effect on amylase secretion. The dopamine receptor antagonists pimozide, chlorpromazine, haloperidol and droperidol as well as SKF 38393 all effectively inhibited dopamine-induced amylase secretion without affecting the enzyme release caused by noradrenaline. The D-2 antagonist sulpiride was without effect on both dopamine- and noradrenaline-stimulated secretion. The dopamine-induced secretion was also significantly blocked by the non-selective beta-blocker propranolol as well as by beta 1- and beta 2-selective antagonists. Several alpha-antagonists were all partial blockers of dopamine-stimulated amylase secretion. In contrast, the noradrenaline-evoked amylase release was exclusively abolished by propranolol and beta 1-selective antagonists. The results suggest that the dopamine- and noradrenaline-induced amylase secretion are activated via different receptor systems, and that dopamine stimulation is mainly a postsynaptic D-1 effect and only to a minor extent due to presynaptic interaction. PMID- 2580722 TI - Pharmacology of harmalan (1-methyl-3,4-dihydro-beta-carboline). AB - Harmalan is presumably formed in vivo as an intermediate product of the biosynthesis of harman as well as tetrahydroharman. The pharmacological effects of harmalan as well as its affinity towards benzodiazepine, 5-HT2 and tryptamine binding sites were investigated in the present study. Harmalan induced clonic convulsions which were antagonized by diazepam. Receptor binding experiments as well as combined treatments with antagonists point to an interaction which involves neither benzodiazepine nor 5HT2 receptor sites but rather tryptamine binding sites. Good agreement was found between the potency of harmalan to increase spontaneous motor activity and the affinity to the tryptamine binding sites when compared with the effects of tryptamine in both tests. In the light dark-chamber test for predicting anxiolytic effects of drugs, harmalan elicited opposite effects to diazepam. The results of combined treatment also suggested an interaction of both compounds not involving benzodiazepine receptors. Tryptamine binding sites seemed to play no role since the amine was inactive under these conditions. Thus, harmalan induces several tryptamine agonistic effects and others not involving tryptamine binding sites. PMID- 2580723 TI - Does brain 5-HIAA indicate serotonin release or monoamine oxidase activity? AB - The question of whether serotonin is deaminated by MAO before it can be released or after release has occurred was investigated by studying the 5-HT behavioral syndrome in acutely reserpinized rats. The release of serotonin from vesicles by reserpine does not produce the serotonin behavioral syndrome which is an in vivo index of serotonin release and receptor activation. However, if rats are first pretreated with a nonselective monoamine oxidase inhibitor (e.g., tranylcypromine), the injection of reserpine is followed by symptoms which are characteristic of the behavioral syndrome including forepaw treading, hindlimb abduction and head weaving. Neither selective MAO-A or -B inhibition with clorgyline or deprenyl, respectively, nor inhibition of serotonin reuptake with fluoxetine prior to reserpine produced the serotonin behavioral syndrome. However, the combination of clorgyline and deprenyl followed by reserpine does so. These behavioral data along with neurochemical analyses of serotonin and 5 hydroxyindoleacetic acid levels lead to the conclusion that serotonin does not have to be released before it is metabolized to 5-hydroxyindoleacetic acid. Consequently, the levels of 5-hydroxyindoleacetic acid in brain reflect MAO activity and not serotonin release or utilization. PMID- 2580724 TI - Studies on beta-adrenoceptors of purified mast cells from guinea-pig lung. AB - Ovalbumin-induced histamine release from passively sensitized monodispersed cells (2-4% mast cells) or purified mast cells (50-78%) from guinea-pig lung was inhibited by isoproterenol and sulfonterol and their relative potencies or maximum responses were similar in both cases. The apparent dissociation constant for butoxamine was also independent of mast cell purity. The results indicate that beta-adrenoceptors mediating histamine release inhibition from lung are localized to mast cells and act independently of other cell types. PMID- 2580725 TI - Pharmacological evidence that the non-neuronal diazepam binding site in primary cultures of glial cells is associated with a calcium channel. PMID- 2580726 TI - Interaction between serotonergic and dopaminergic systems detected in striatum by differential pulse voltammetry. PMID- 2580727 TI - [Studies on implantation traces in rats. I. Size, observation period and staining]. AB - The implantation traces of early embryonal death and abortion in rats induced by some drugs were studied. Early embryonal death and abortion were caused by intraperitoneal injection of 15 mg/kg of busulfan on the 7th day of gestation or 40 mg/kg of 6-mercaptopurine on the 7th and 8th day of gestation. The observation period and staining of the implantation traces were investigated. Early dead embryos and placentas were delivered between the 20th and 24th day of gestation. These were eaten by the dams. The implantation traces of abortion or early embryonal death, and those of normal delivery were able to be identified up to the 120th day and 500th day after extraction, respectively. The implantation traces of abortion were smaller in the three experimental groups. All kinds of implantation traces were stained distinctly with 10% ammonium sulfide, 0.2% sodium hydroxide and 2% potassium ferrocyanide. In this staining method, sodium hydroxide has an excellent effect on the staining of implantation traces. Specimens washed in water after being stained with sodium hydroxide and fixed in formalin can be preserved without discoloration for a long period of time. PMID- 2580728 TI - [Histochemical demonstration of proteins, lipids and polysaccharides in Japanese monkey oocytes]. AB - A histochemical study of proteins, lipids and polysaccharides was carried out in the oocytes of Japanese monkey (Macaca fuscata) during development of follicles. There were a small number of protein granules reactive to acrolein-Schiff in the cytoplasm of oocytes from primordial, secondary and vesicular follicles, while there were no lipid droplets, granules of neutral polysaccharides or acid polysaccharides in the cytoplasm. Proteins reactive to acrolein-Schiff, neutral polysaccharides reactive to periodic acid-Schiff and acid polysaccharides stainable with alcian blue were observed in the zona pellucida of the oocytes of secondary and vesicular follicles. The zona pellucida contained sudanophilic lipids composed of neutral fats and lipoids, besides the proteins and polysaccharides. PMID- 2580729 TI - Characterization of fibroblastic stromal cells from murine bone marrow. AB - Several properties of fibroblastic colony-forming units (CFU-F) from murine bone marrow and their in vitro progeny were evaluated. CFU-F had a high buoyant density relative to total bone marrow cells; they were noncycling in situ and adhered to nylon wool. The fibroblastic cells stained positively for fibronectin, lipid, alkaline phosphatase, and nonspecific esterase, while phagocytosis assays were negative, and ultrastructural analysis failed to reveal desmosomes. These properties contrasted bone-marrow-derived fibroblastic cells to both endothelial cells and macrophages. Fibroblastic cells derived from several hemopoietic organs and skin were screened for antigenic determinants present on hemopoietic cells using monoclonal antibodies. Mac-1 and B220 were absent from all fibroblastic cells studied, whereas the Forsmann and Pgp-1 antigens were always present. Thy-1 was not detected on bone-marrow-derived fibroblasts, but was present on fibroblastic cells derived from other sources. T200 was found on all hemopoietic organ-derived fibroblastic cells, but not on those derived from blood and skin. Thus, analysis of antigenic determinants allowed distinction between fibroblastic cells from different organs. PMID- 2580730 TI - Molecularly cloned and expressed murine T-cell gene product is biologically similar to interleukin-3. AB - Clonal lines of mouse inducer ly1+ly2- inducer T-lymphocytes that depend for growth upon interleukin-2 have been demonstrated to produce a factor that stimulates colony formation by bone marrow granulocyte-macrophage (GM-CFUc) progenitor cells and replication of factor-dependent mast cell/basophil and multipotential hematopoietic cell lines in vitro. The molecularly cloned and expressed gene product for this growth factor demonstrates the following activities in vitro: using fresh bone marrow or purified subpopulations of nonadherent cells from murine continuous bone marrow cultures as target cells: stimulation of colony formation by GM-CFUc, mast cell progenitor cells, multipotential granulocyte/erythroid/megakaryocyte/macrophage progenitor cells (CFU-GEMM) colonies, erythroid progenitor cells forming macroscopic bursts (BFUe), and megakaryocyte progenitor cells (CFU-mega). The gene product also supports growth of previously reported mast cell growth-factor-dependent cell lines and several classes of interleukin-3 (IL-3)-dependent hematopoietic progenitor cell lines that are multipotential (neutrophil/basophil/eosinophil or neutrophil/basophil/erythroid); or committed to granulocyte-macrophage, or mast cell/basophil differentiation. The gene product does not detectably support replication of IL-2-dependent murine T-cell lines. The biologic activity of the gene product was inhibited greater than or equal to 90% by rabbit antisera prepared against purified interleukin-3. The data indicate that this T-cell derived lymphokine gene product is biologically very similar to interleukin-3. PMID- 2580731 TI - Differential cytotoxic activity of chemotherapy agents on colony-forming cells from human tumors and normal bone marrow in vitro. AB - We have compared the in vitro differential killing efficacy of doxorubicin, 5 fluorouracil, cis-platinum, etoposide, and bleomycin on human tumor cells in a new adhesive tumor cell culture system (ATCCS), and on normal bone marrow granulocyte-macrophage colony-forming units (GM-CFUC) in culture. All of the above chemotherapy agents were tested with continuous exposure against tumor cells and GM-CFUC. In addition, bleomycin was also tested with a short (60 min) exposure against GM-CFUC. In order to determine chemosensitivity against all five drugs, 48 tumor specimens from patients with heterogeneous tumor types were tested in the ATCCS. Each drug was tested at three different concentrations corresponding to their lethal doses against GM-CFUC. Our results show that all five drugs exhibited a dose-response relationship against tumor cells and GM CFUC. Bleomycin also showed a pronounced GM-CFUC-sparing quality with 60-min exposure even at very high concentrations (86% survival of GM-CFUC at 10 micrograms/ml and 48% at 50 micrograms/ml). In addition, it has a high tumor response rate with continuous exposure at low concentrations (67% at GM-CFUC LD5 and 91% at LD40). These data suggest that the comparison of differential cytotoxicity of chemotherapy drugs between tumor cells and bone marrow cells may serve as a model to select agents suitable for in vitro chemotherapy of bone marrow for the purpose of autologous bone marrow transplantation. In particular, bleomycin appears very attractive and deserves further investigation. PMID- 2580733 TI - Comparison of the effects of sciatic nerve crush or resection on the proteins of fast axonal transport in rat dorsal root ganglion cell axons. AB - Proteins of fast axonal transport in rat sciatic nerve axons were separated and characterized by SDS-polyacrylamide gel electrophoresis and fluorography, after injection of L-[35S]methionine into the dorsal root ganglion. The effects of crushing or resecting the sciatic nerve on the relative labeling of specific polypeptide bands were compared. Initially, both types of axon injury produced the same response, but after 3 weeks there was a partial return to normal composition in crushed nerves. In resected nerves, the changes characteristic of axon injury persisted beyond 7 weeks. Behavioral testing showed that crushed nerves reinnervated foot skin, whereas no reinnervation was detected after resection. We conclude that in sensory neurons, as in several other neuronal types, the restoration in normal composition of fast-transported protein after axon injury depends on reinnervation of target tissues. This aspect of the cell body reaction to injury seems to be regulated by a retrograde trophic interaction with the target. PMID- 2580732 TI - Sex differences in long-term gonadectomized rats: monoamine levels and [3H]nitroimipramine binding in brain nuclei. AB - The levels of norepinephrine, dopamine, serotonin and the serotonin metabolite 5 hydroxyindoleacetic acid were measured in microdissected brain nuclei from long term gonadectomized male and female rats. Females had 50 and 120% higher levels of serotonin in the anterior hypothalamic nucleus (AH) and arcuate-median eminence (AR-ME), respectively. No significant differences in norepinephrine, dopamine or 5-hydroxyindoline acetic acid were found in any of the brain nuclei sampled. The differences in serotonin content do not appear to result from a sexually dimorphic distribution of serotonin nerve terminals since quantitative autoradiography of 3H-nitroimipramine revealed no differences in binding between the sexes in the AH or AR-ME. PMID- 2580735 TI - Substance P-like immunoreactivity in the frog dorsal root ganglia. AB - The distribution of substance P-like immunoreactivity was studied in the thoracic dorsal root ganglia of the frog Rana esculenta by immunohistochemistry. Substance P-like immunoreactivity was contained in approximately 50% of primary sensory neurons. The immunoreactive fibers arising from the cell bodies are collected in small bundles within the ganglia neuropil before entering the central and peripheral roots. PMID- 2580736 TI - Sympathectomy enhances the substance P-mediated breakdown of the blood-aqueous barrier in response to infrared irradiation of the rabbit iris. AB - Rabbits were subjected to infrared irradiation of the iris 1 month after unilateral cervical sympathectomy. The resulting breakdown of the blood-aqueous barrier was greatly enhanced on the sympathectomized side. In contrast, the response to intravitreally injected substance P (SP) was the same in both eyes. The enhancement of the response to IR irradiation could be abolished by pretreatment with an SP antagonist, (D-Pro2, D-Trp7,9)-SP. PMID- 2580737 TI - Evidence for a Ca2+-independent hydrolysis of phosphatidylinositol 4,5 bisphosphate in neuron-like cell line NG108-15 cells. AB - The addition of bradykinin to 32Pi-labeled neuroblastoma X glioma hybrid NG108-15 cells caused a substantial loss of radioactivity from phosphatidylinositol 4,5 bisphosphate (PI-4,5-P2). The bradykinin-induced hydrolysis of PI-4,5-P2 was almost equally observed even when extracellular Ca2+ was depleted with EGTA (100 microns). On the other hand, high K+ depolarization of the cells, which allows Ca2+ influx through voltage-dependent Ca2+ channels, failed to induce any significant decrease in the radioactivity of PI-4,5-P2. These data indicate that the bradykinin-stimulated PI-4,5-P2 hydrolysis in NG108-15 cells is independent of extracellular Ca2+ and also that PI-4,5-P2 hydrolysis is not stimulated by an elevation of intracellular Ca2+ concentration. PMID- 2580739 TI - The encephalitogenic protein of myelin forms hexamers in which the polypeptides have a pleated-sheet structure. AB - Sedimentation equilibrium data are shown to be consistent with the existence in solution of an equilibrium between monomers and hexamers of bovine myelin basic protein, without significant accumulation of intermediates. At low concentrations circular dichroism spectra were indicative of an aperiodic coiled secondary structure. At higher concentrations, where the protein self-associates, they showed formation of a beta-pleated sheet conformation. At low molar ratios myristoyllysophosphatidylcholine promotes protein self-association and the concomitant conformational transition. The data are consistent with the existence of an equilibrium mixture of relatively unstructured monomers and hexamers in which the polypeptides have a well-defined three-dimensional structure. PMID- 2580738 TI - 3'-Fluoro-2',3'-dideoxyribonucleoside 5'-triphosphates: terminators of DNA synthesis. AB - It is shown that dNTP(3'F) are terminators of DNA synthesis and may serve as very effective tools for DNA sequencing with E.coli DNA polymerase I and AMV reverse transcriptase. The dNTP(3'F) are found to be chain terminator substrates for calf thymus terminal deoxyribonucleotidyl transferase but not for calf thymus DNA polymerase alpha. The optimal dNTP(3'F) concentration for DNA sequencing by DNA polymerase I is found to be an order of magnitude lower than that of ddNTPs. dNTP(3'F) produce a more clear sequence pattern than do ddNTPs. PMID- 2580740 TI - Selective labeling of beef heart cytochrome oxidase subunit III with eosin-5 maleimide. AB - Cytochrome c oxidase has been isolated from beef heart mitochondria and labeled with the fluorochrome eosin-5-maleimide (EMA) after pretreatment with mersalyl. On SDS-polyacrylamide gels, EMA fluorescence and absorption occurred at a single band corresponding to subunit III. Since only Cys 115 of the two cysteinyl residues of subunit III had been shown to be reactive towards water-soluble SH reagents, it was concluded that this residue was the one labeled by EMA. The EMA/enzyme ratio was about 1. Gel filtration experiments have shown that upon treatment with dicyclohexylcarbodiimide, subunit III was loosened from the complex; this result suggests that the inhibitory effect of dicyclohexylcarbodiimide on the H+-translocation activity may be related to such a phenomenon. PMID- 2580734 TI - Neuronal control of brain microvessel function. AB - Cerebral capillary endothelium forms a barrier limiting and controlling the movement of ions and solutes between blood and brain. Recent anatomical, physiological and biochemical studies have suggested the possibility that capillary function may be directly controlled by neuronal structures. Alterations in neuronal systems involved in the regulation of microcirculation may account for microvascular dysfunctions which occur in different pathologic conditions. PMID- 2580741 TI - Postcricoid carcinoma: a retrospective study of 13 patients. AB - Thirteen consecutive patients presenting with squamous cell carcinoma in the postcricoid region (PCC) are studied and details of their age, sex, TNM status, treatment and results are analysed. Follow-up ranges from 33 months to 11 years. Three patients presented with cervical node involvement and 2 of these remain disease free without surgical intervention, at 33 months and 9 years. The principal treatment policy has been the combination of multi-agent chemotherapy with radical radiotherapy, reserving wide excision surgery for patients with residual or recurrent carcinoma. Only 4 patients underwent pharyngolaryngectomy, one radical neck dissection was performed and 7 of the 13 patients have remained free of disease for more than 3 years. PMID- 2580742 TI - Tolerance and B cell repertoire establishment. AB - We have probed the mechanism by which immature B cells are uniquely susceptible to antigen-induced inactivation. Our studies have demonstrated that this tolerance trigger is an active process that requires both energy metabolism and the biosynthesis of various macromolecules, including protein, RNA, and DNA. However, the tolerance trigger is resistant to inhibitors of patching and capping, as well as an inhibitor of mitosis. The tolerance trigger requires a high-affinity interaction between a multivalent antigen and the cells' Ig receptor, but apparently does not require interactions with other cell surface molecules, or interactions with T cells or macrophages. Our efforts to demonstrate the physiological applicability of this tolerance trigger have concentrated on an attempt to demonstrate potentially self-reactive cells within the immature bone marrow population that do not appear in the mature splenic B cell population. To date we have identified prereceptor B cells of several specificities whose frequency is much lower in the spleen and whose elimination appears to involve tolerance rather than antiidiotypic regulation. However, the demonstration that such cells are eliminated by contact with self-antigens has not as yet been accomplished. PMID- 2580743 TI - [Role of enzymes of the digestive glands in the regulation of their secretion]. PMID- 2580744 TI - [Effect of natural neurotensin and its analog on gastric secretion and levels of various peptides in dog blood]. AB - I.v. administration of neurotensin and its analogue DTch1I--neurotensin considerably decreased stomach secretion induced with pentagastrin but did not suppress stomach secretion induced with histamine, neither a microapplication of 10 micrograms in 3 microliter of neurotensin affected the secretion whereas the dose 50 micrograms in 3 microliter decreased both volume and acidity of the juice. I.v. administration of neurozensin increased the gastrin, neurotensin and the substance P contents in the dog blood. Microapplication of neurotensin to the globus pallidus with simultaneous i.v. administration of histamine increased the level of the serum gastrin. PMID- 2580745 TI - Protein-linked oligosaccharide implicated in cell-cell adhesion in two Dictyostelium species. AB - Monoclonal antibody d-41, previously shown to block in vitro cell-cell adhesion in aggregating Dictyostelium discoideum, also blocks adhesion in aggregating D. purpureum. In both species the antibody reacts with proteins with Mr approximately 80,000, 37,000, and 27,000, presumed to be glycoproteins since the d-41 epitope is destroyed by periodate oxidation but unaffected by extensive Pronase digestion. Polyclonal antibodies raised against the mixture of d-41 reactive glycoproteins that had been purified by immunoaffinity chromatography are potent inhibitors of D. discoideum adhesion, and adhesion-blocking activity is neutralized extensively and equivalently by each of the purified glycoproteins from D. discoideum with which d-41 reacts. In contrast, polyclonal antibodies raised against the same purified glycoproteins after they had been oxidized with periodate do not block cell-cell adhesion although they react with the glycoproteins with Mr approximately 80,000, 37,000, and 27,000 and bind as extensively to the surface of aggregating D. discoideum cells as do the adhesion blocking polyclonal antibodies. When taken together, these results raise the possibility that some component of the d-41 binding oligosaccharide participates in cell-cell adhesion. PMID- 2580747 TI - Repetitive sequence transcripts and U1 RNA in mouse oocytes and eggs. AB - Others have reported that about two-thirds of the polyadenylated RNA of sea urchin or frog eggs contains short interspersed repetitive sequence transcripts, a much larger proportion than that found in mRNA of somatic cells. Thus, it appears that incompletely processed transcripts accumulate in these oocytes. Also, in what may be a related phenomenon, the nuclear concentration of U1 RNA (involved in processing hnRNA) decreases during growth of frog oocytes. To pursue this question in mammals, Northern blots of RNA from mouse oocytes and eggs collected before and after meiotic maturation were probed with genomic clones containing rodent Alu-equivalent sequences. The Alu sequence is the predominant short interspersed repetitive element in the genome and is abundant in hnRNA. When compared on the basis of mRNA content, the oocyte and egg RNA contained less short repetitive sequence transcripts than liver or brain cytoplasmic RNA. Using a U1 RNA-specific probe, the concentration of U1 RNA in mouse oocyte nuclei was found to be quite similar to that in somatic cells, and U1 RNA was stable during meiotic maturation. These results suggest that processing of transcripts in mouse oocytes does not possess the unusual features observed in lower animals. PMID- 2580746 TI - Adhesion mutants of Dictyostelium discoideum lacking the saccharide determinant recognized by two adhesion-blocking monoclonal antibodies. AB - A mutant of Dictyostelium discoideum, strain HL260, was isolated based on its failure to bind d-41, a monoclonal antibody that blocks developmentally regulated cell-cell adhesion. The mutant fails to normally acquire cell-cell adhesion as assayed with cells shaken in 10 mM EDTA, but aggregates and and constructs fruiting bodies. Other mutant strains, HL216 and HL220, previously shown to have impaired cell-cell adhesion, also lack the determinant that binds d-41. The three strains all carry mutations in a gene designated mod B, which directs a post translational modification of several developmentally regulated D. discoideum glycoproteins. Diploids formed between independent mod B mutant haploid strains also lack this determinant and show marked impairment of cell-cell adhesion in EDTA, indicating that mutations in mod B, rather than other mutations not shared by the haploid strains, are related to the adhesion defect. The results are consistent with other evidence that an oligosaccharide carried on several developmentally regulated glycoproteins plays an essential role in EDTA-resistant cell-cell adhesion in D. discoideum. However, this type of adhesion is not essential for morphogenesis in that the only defect detected thus far in mod B mutant strains is that they construct relatively smaller fruiting bodies that contain fewer spores. PMID- 2580748 TI - Effects of lysosomal inhibitors on 125I-insulin and 125I-asialofetuin degradation by the isolated, perfused rat liver and isolated rat hepatocytes. AB - To further evaluate the role of the lysosomal system in insulin degradation, we have compared the effects of inhibitors of lysosomal function on the degradation of 125I-insulin with 125I-asialofetuin, a lysosomally targeted molecule, by the intact, perfused rat liver and the isolated rat hepatocyte. The inhibitors employed were chloroquine (125 microM), NH4Cl (10 mM), and leupeptin (50 micrograms/ml). In the intact, perfused liver the observed inhibition of 125I asialofetuin degradation at 30 min was as follows: chloroquine, 38%; NH4Cl, 32%; and leupeptin, 86%. Chloroquine also inhibited 125I-insulin degradation in the intact, perfused liver (29%), but NH4Cl and leupeptin had no effect. Using the isolated hepatocyte, the observed values for inhibition of 125I-asialofetuin at 60 min were: chloroquine, 85%; NH4Cl, 76%; and leupeptin, 81%. Chloroquine produced a 28% inhibition of 125I-insulin degradation, while NH4Cl and leupeptin had no effect. Chloroquine and NH4Cl decreased cell-associated radioactivity when isolated hepatocytes were incubated with 125I-asialofetuin (leupeptin had no effect), whereas chloroquine caused a 107% increase in cell-associated radioactivity when 125I-insulin was added to the incubation media (NH4Cl and leupeptin had no effect). These results indicate that the effects of chloroquine on insulin degradation are an extralysosomal action and that lysosomes appear not to be involved in the physiologic degradation of the insulin molecule. PMID- 2580749 TI - In vitro preparation of nonenzymatically glucosylated human transferrin, alpha 2 macroglobulin, and fibrinogen with preservation of function. AB - Human transferrin, alpha 2-macroglobulin, and fibrinogen were incubated with [3H] glucose. After a 7-day, 37 degrees C incubation at 20 mM glucose, transferrin incorporated 1.1 mol of glucose/mol protein; alpha 2-macroglobulin, 10 mol of glucose/mol; and fibrinogen, 3.8 of glucose/mol, or approximately 14 mumol of glucose/g for each protein. These results were the same for glucose labeled in the 1 or 6 position. No radiolabel was incorporated into the proteins during incubations with glucose labeled in the 2 position. The rate and extent of iron binding were identical for both glucosylated and nonglucosylated transferrin. Glucosylated transferrin bound to Wil-2 human lymphoblast cells with a Kd = 33 nM and receptor number of 3.4 X 10(5) receptors/cell; nonglucosylated transferrin with a Kd = 31 nM and receptor number of 3.9 X 10(5) receptors/cell. Glucosylated and nonglucosylated alpha 2-macroglobulin showed the same conformational change as determined on native PAGE after reaction with trypsin, plasmin, or methylamine and had the same activity in the Ganrot assay after reaction with trypsin or plasmin. The clearance of 125I-labeled, methylamine-treated alpha 2-macroglobulin from the mouse circulation was identical for both glucosylated and nonglucosylated alpha 2-macroglobulin, t1/2 = 3 min. alpha 2-Macroglobulin that was first glucosylated then reacted with methylamine bound to mouse peritoneal macrophages with a Kd of 2.5 nM and receptor activity of 370 fmol/mg cell protein. alpha 2-Macroglobulin that was first reacted with methylamine and then glucosylated bound with a Kd of 3 nM and receptor activity of 320 fmol/mg cell protein. Glucosylated fibrinogen had the same clotting time as control fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580750 TI - The effects of neurotoxicants on kindling and kindled seizures. AB - The application of a constant-amplitude electrical stimulation to many parts of the brain leads to the expression of progressively more severe epileptiform responses. The process of acquisition is termed kindling, and the acquired response is termed the kindled seizure. This state has been used in a number of important ways including the modeling of human epilepsy and behavioral disorders, the testing of drugs for anticonvulsant effects, and, more recently, the examination of hyperexcitability states induced by pesticides and other environmental chemicals. This report discusses attributes of kindling and kindled seizures, examines possible mechanisms responsible for them, and summarizes drug and chemical effects on them. Kindling is powerfully accelerated by exposures to only a few substances, among the most effective of which are the chlorinated hydrocarbon insecticides, lindane and dieldrin. An analysis of the acceleration of kindling produced by lindane suggests that the threshold concentration in the nervous system for kindling enhancement is approximately 0.4 microgram/g (1.4 X 10(-9) mol/g). PMID- 2580751 TI - Mediators of increased collagen synthesis in fibrosing organs. PMID- 2580752 TI - The many faces of an increase in lung collagen. AB - Many toxic chemicals have been shown to produce an increase in lung collagen. Biochemical measurements of total lung hydroxyproline are a convenient method to quantitate and to follow disease processes associated with such an increase. However, biochemical measurements alone do not distinguish various pathological lesions and histology is needed to provide additional important information. Cell kinetic studies enhance histopathology in showing the dynamics of cell proliferation and tissue renewal. When these methods of studying lung collagen are applied to different toxic agents, such as butylated hydroxytoluene, methylcyclopentadienyl manganese tricarbonyl, CdCl2, or anticancer drugs, different patterns of hydroxyproline accumulation and cellular kinetics are revealed. It is speculated that the development of fibrotic lung disease may be at least partially determined by the initial lesion and that quantitative analyses of cell kinetic patterns help to understand and to predict the nature and evolution of disease processes. PMID- 2580753 TI - Regulatory peptides (glucagon, somatostatin, substance P, and VIP) in the brain and gastrointestinal tract of Ambystoma mexicanum. AB - The concentrations of immunoreactive components of glucagon, somatostatin, substance P, and vasoactive intestinal polypeptide (VIP) in the brain, stomach, and gut of the neotenic Mexican axolotl (Ambystoma mexicanum) were determined by radioimmunoassay using antibodies of defined regional specificity. The molecular forms of the immunoreactive components were analyzed by high-performance liquid chromatography (HPLC). The concentrations and molecular forms of somatostatin and VIP in axolotl brain were comparable to the concentrations in mammals but the substance P-like immunoreactivity was resolved by HPLC into components with the retention times of physalaemin and substance P together with their oxidized forms. No glucagon-like material was detected in the axolotl brain. The concentrations of substance P and VIP in the A. mexicanum digestive tract were appreciably lower than in the mammalian digestive tract and the VIP-like material did not coelute with porcine VIP. Somatostatin-14 represented the major molecular form in the axolotl stomach and gut. The distribution and molecular properties of the glucagon-like peptides in the axolotl digestive system were markedly different from these parameters in mammalian gut. Glucagon-like material is present only in low amounts in porcine and human stomach and, the concentration of enteroglucagon (N-GLI) in the gut is at least fiftyfold greater than pancreatic glucagon (C-GLI) concentrations. The axolotl stomach, in contrast, contains high levels of glucagon-like immunoreactive material and, in both stomach and gut, the levels of C-GLI and N-GLI were comparable. The glucagon-like material was heterogeneous on HPLC and was resolved into two major components but no component with the retention time of mammalian glucagon was present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580755 TI - [Hygienic regulation of beta-phenylethyl alcohol content of reservoir water]. PMID- 2580754 TI - On biological functions mapping to the heterochromatin of Drosophila melanogaster. AB - We examined the behavior of an autosomal recessive maternal-effect mutation, abnormal-oocyte (abo), that is located in the euchromatin of the left arm of chromosome 2. When homozygous in females, abo results in a marked reduction in the probability that an egg produced by a mutant mother will develop into an adult. However, this probability is increased if the fertilizing sperm delivers to the egg either a normal allele of the maternal-effect gene or a specific type of heterochromatin (called ABO) that is located in small regions of the X and Y chromosome constitutive heterochromatin as well as in some autosomal heterochromatin. These regions, moreover, all react to Hoechst 33258 fluorescent dye identically and specifically. The amelioration of the maternal effect produced by this heterochromatin differs temporally from that caused by the normal allele of the euchromatic gene: the heterochromatin reduces only precellular blastoderm mortality, whereas the normal allele of the euchromatic gene reduces only postblastoderm mortality. Thus, although the genome of the preblastoderm Drosophila embryo is apparently mostly silent, the ABO-containing heterochromatin functions at this early time. Finally, preliminary data indicate that abo is but one member of a cluster of linked genes, each of which interacts with its own normal allele and with a different, locus-specific, heterochromatic factor. From these observations, it appears that Drosophila heterochromatin contains developmentally important genetic elements, and that a functional concomitant of heterochromatic location is gene action at a developmental stage during which the activity of the euchromatic genome is as yet undetectable. Some general implications of these inferences are considered. PMID- 2580756 TI - [Normal values of dopamine, noradrenaline, adrenaline, and 5-hydroxyindoleacetic acid in pregnancies of different gestational ages]. PMID- 2580757 TI - The effectiveness of multidrug treatment by bleomycin, methotrexate, and cis platinum in advanced vaginal carcinoma. AB - A case of a female with advanced squamous carcinoma of the vagina is presented. Complete disappearance of the primary tumor and involved inguinal lymph nodes was achieved with three courses of the cis-platinum-containing chemotherapy regimen BMP administered prior to radiotherapy. The encouraging result obtained warrants the use of this combined treatment modality in other patients. PMID- 2580758 TI - Endodermal sinus tumor and embryonal carcinoma of the ovary in children. AB - The clinicopathological features of 26 pure endodermal sinus tumors (EST) and for embryonal carcinomas of the ovary occurring in children under age 15 years in Britain over the period 1962-1978 are described. Endodermal sinus tumor has shown a significant increase (P less than 0.001) over the 17-year period considered. Compared to controls, EST and embryonal carcinoma have not shown an association with the use of hormones or tranquilizers during pregnancy, with radiological investigations, or with infections in pregnancy though the numbers of cases studied were very small. The histological and immunohistological features of EST and embryonal carcinoma in children do not differ substantially from the descriptions of these tumors in adolescents and adults. Using the FIGO staging classification 23% were Stage I tumors; 3% were Stage II; 70% were Stage III; and 3% were Stage IV neoplasms. The 5-year actuarial survival rate was 39% among 26 cases of EST and 1 of the 4 cases of embryonal carcinoma also survived for 5 years. Clinical stage at diagnosis was the only indicator of prognosis, but the introduction of polychemotherapy (vincristine, actinomycin-D, cyclophosphamide/cis-platinum, vincristine, bleomycin) resulted in long-term survival in 7 of 7 cases of EST (2 Stage I and 5 Stage III) and 1 of 2 cases of embryonal carcinoma (Stage III). Radiotherapy appears to have little role to play in the treatment of pure EST or embryonal carcinoma. PMID- 2580760 TI - Radiotherapy of primary carcinoma of the vagina: management and results of different therapy schemes. AB - Three hundred and sixty-two cases of primary vaginal carcinoma were treated at the Irradiation Department of the University Clinic for Obstetrics and Gynecology, Vienna, from 1950 to 1977. As the method of choice an individually dosed, fractioned, and protracted radium-telecobalt therapy was employed. Comparing the last period analyzed (1971-1977) with another period 20 years earlier (1951-1956), a marked increase of advanced stages and older patients can be observed. These changes are reflected in the 5-year remission rate: in the total population it was 39.8%, as compared to 32% for the period from 1971 to 1977. For a group of 99 patients, who were treated between 1971 and 1977, the therapeutic effect of different therapy schemes is reported. The benefit of teletherapy is remarkable for advanced states, whereas for stages I and II an intrauterine application may be of importance. The complication rate amounted to 8% recto- or vesicovaginal fistulas and 41% and 43% cystitis and proctitis. The central importance of gynecological screening, especially for older women, is emphasized. PMID- 2580759 TI - Immunocytochemical evidence of heterogeneous origin of alpha-fetoprotein in immature teratoma of the ovary. AB - alpha-Fetoprotein (AFP) has been found to be clinically important in the management of patients with gynecologic malignancies. Serum AFP levels are used as tumor markers for ovarian tumors, namely endodermal sinus tumors (EST) and embryonal tumors. In two cases of immature teratoma of the ovary without a yolk sac component, evidence for AFP production was found in a wide variety of cells of both endodermal and ectodermal origin suggesting a heterogeneous origin of AFP. To complement this finding, a summary of the ontology of AFP along with current and potential uses of an antigenically active tumor marker are presented. PMID- 2580761 TI - A longitudinal study of cyclic nucleotide phosphodiesterase activity and its relationship with nucleic acid content in the myometrium of cynomolgus monkeys (Macaca fascicularis) between days 39 and 162 of gestation. AB - Cyclic AMP and cGMP phosphodiesterase (PDE) activities and nucleic acid contents were assayed in crude homogenates prepared from biopsies excised between days 39 and 162 of gestation (normal full length of gestation: 165 days) in outer and inner layers of the macaque myometrium. In both layers, kinetic analysis of PDE indicated high (apparent Km 2 X 10(-6) M) and low (apparent Km 2 X 10(-5) M) affinity component for each substrate. When measured in high-affinity conditions, specific activities were elevated around day 40 and beyond day 130 of gestation. By contrast, low values were observed between days 50 and 100. They were related to the decrease of the Vmax values (expressed either per milligram protein or per microgram DNA). No significant differences were observed between outer and inner layers. Variations of tissue DNA and RNA were demonstrated throughout gestation indicating that both hyperplasia and hypertrophy were involved in uterine growth. Unlike DNA, RNA content (and consequently the RNA:DNA ratio) in the inner layer always remained above the values of the outer layer. In both layers, the RNA:DNA ratio, which presumably reflects the rate of protein synthesis and the PDE activity, reached maximum values at the same time. PMID- 2580762 TI - Early detection of pregnancy by new beta-hCG monoclonal urine test. AB - 1,066 urine samples were assayed by beta-human chorionic gonadotrophin (beta-hCG) monoclonal pregnancy test with a sensitivity of 150 IU hCG/l. Tests were performed in 5 independent laboratories and results were compared with those of pregnancy tests which were used routinely. Urine samples which showed discordant results under evaluation were reassayed for beta-hCG using radioimmunoassay. 569 urine samples were from nonpregnant women, and a consistent result with comparison pregnancy tests was achieved in 97.19% of urine samples. The trial test from 389 urine samples of pregnant women was 99.49% in accordance with routine pregnancy tests. Results from 108 urine samples of women over 40 years of age indicate the high specificity of the new beta-hCG monoclonal pregnancy test. Titration experiments showed 63% positive tests at 150 IU beta-hCG/l. Data presented combine to suggest that this new monoclonal pregnancy test is a valuable aid in diagnosing early pregnancy. It may also be used in the diagnosis of tubal pregnancy and in other ectopic processes. PMID- 2580763 TI - Differential staining of cryptosporidia by aniline-carbol-methyl violet and tartrazine in smears from feces and scrapings of intestinal mucosa. PMID- 2580765 TI - Morphological characteristics of striatonigral neurons. PMID- 2580764 TI - [Effect of Saiboku-to, a blended Chinese traditional medicine, on Type I hypersensitivity reactions, particularly on experimentally-caused asthma]. AB - Effect of Saiboku-to, which has been used for the therapy of bronchial asthma, on Type I hypersensitivity reactions was investigated. Forty eight-hr homologous PCA and antigen-induced histamine release in peritoneal cavities of rats passively sensitized with anti-DNP-As . IgE serum tended to be inhibited by the oral administration of Saiboku-to. On the other hand, 7-day homologous PCA in guinea pigs mediated by anti-BPO-BGG . IgE serum was significantly inhibited with 200 and 500 mg/kg of Saiboku-to given orally 2 hr prior to challenge. In experimentally caused asthma in guinea pigs, 200 mg/kg of Saiboku-to dramatically inhibited decreases in the rate and volume of respiration, and 500 mg/kg of the drug inhibited even an increase in the ratio of expiration time to inspiration time. The Schultz-Dale reaction in guinea pig tracheal muscle was significantly inhibited by the pretreatment with 10(-4) g/ml of Saiboku-to. The antigen-induced histamine release from sensitized guinea pig lung tissue was inhibited by 10(-6) to 10(-4) g/ml of Saiboku-to in a dose-dependent fashion, though the release of SRS-A was not affected. Saiboku-to did not show an antagonistic effect on allergic mediator-induced contraction in guinea pig ileum. From these results, it is considered that Saiboku-to shows an inhibitory activity on the Type I hypersensitivity reaction through the suppression of histamine release. PMID- 2580766 TI - A screening method for urinary methamphetamine--latex agglutination inhibition reaction test. AB - Methamphetamine in urine samples from abusers was detected by the latex agglutination inhibition reaction test with latex-antibody (Latex-Ab) and latex methamphetamine (Latex-MA) reagents. Anti-methamphetamine antibody was produced in rabbits by immunization with bovine serum albumin (BSA)-methamphetamine conjugate. Latex particles were coated with antibodies or with rabbit serum albumin (RSA)-methamphetamine conjugate to obtain Latex-Ab and Latex-MA reagents, respectively. The results are read at 4-5 min after mixing the latex reagents. The sensitivity of this method for methamphetamine was 0.4 micrograms/ml urine. Methamphetamine analogs (methylephedrine, amphetamine, phentermine, methoxyphenamine, ephedrine, beta-phenylethylamine, OH-methamphetamine, OH amphetamine, and OH-ephedrine) all cross-react in varying degrees, while glucosiurea and albuminurea give false positive results in the tests. Though attention must be paid to these effects this simple and rapid test is suitable for the mass screening of urine samples. PMID- 2580767 TI - [Arrhythmias in hypertrophic cardiomyopathy. Significance and therapeutic consequences]. AB - The natural history of the patient with hypertrophic cardiomyopathy is characterized by slow progression of symptoms and left ventricular hypertrophy; severe functional limitation is unusual and encountered only in about 20%. Most of the deaths are sudden and occur irrespective of the functional status of the patient and there are no routine electrocardiographic or hemodynamic measurements indicative of poor prognosis. Sudden death may be associated with syncope and young age at diagnosis as well as with a family history of sudden death. The mechanisms underlying the cause of sudden death have not been clearly elucidated. Although complete heart block may complicate myotomy or myectomy, the development, in an unoperated patient, of symptomatic conduction disease is uncommon. Preexcitation syndromes may be present in a small subpopulation (about 2%), but this appears seldom responsible for sudden death. Outflow tract spasm has also been postulated as a causal factor but the fact that proportionately an equal number of patients with and without ventricular outflow gradients die suddenly, suggests that other mechanisms must be important. Further hypotheses, currently however, without substantiation, have implicated acute changes in diastolic filling or acute myocardial ischemia as causes of sudden death. Recently published studies have stressed the importance of ventricular arrhythmias as a cause of sudden death. Ventricular tachycardia occurs in about 30% of such patients and can be found significantly more frequent in adult patients who die suddenly. In children and adolescents, since they have a lesser incidence of ventricular tachycardia, possibly, other mechanisms are involved. In general, episodes of ventricular tachycardia are asymptomatic and self-limited; the main ventricular rate recorded during 135 episodes in 30 of our patients was 142 beats per minute with an average duration of eight beats. Variable QRS morphology suggests different sites of origin. Due to the marked spontaneous variability, the probability of missing ventricular tachycardia with a single 24 hour continuous ambulatory ECG is 54%; on 96 hours of continuous ECG monitoring the probability can be reduced to 8%. Accordingly, continuous ambulatory ECG monitoring should be carried out for at least 48 to 72 hours. At the time of diagnosis, approximately 7% of the patients have atrial fibrillation. On three days of continuous 24-hour ECG monitoring, about 40% will be found to have atrial fibrillation or supraventricular arrhythmias. The correlation between supraventricular arrhythmias and sudden death is weaker than that of the latter with ventricular arrhythmias.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2580768 TI - In vitro determination of tumour chemosensitivity in haematological malignancies. AB - A four-day tumour chemosensitivity assay of potential use in predicting tumour response to cytotoxic drugs has been developed for haematological cancers. The method comprised isolation of white cells from peripheral blood or bone marrow aspirates, drug exposure and incubation for 4 days. Drug-induced tumour cell kill was assessed by differential staining of live and dead cells such that the former could be morphologically identified. Tumour cell viability was subsequently calculated by reference to an internal standard of fixed duck red blood cells. Over 30 drugs have been tested in vitro, all of which have shown a dose response relationship in vitro and given a good scatter of sensitivities from patient to patient within the concentration ranges tested. In 27 cases where the in vitro chemosensitivity could be compared with the in vivo response, there were 7 true positive comparisons (sensitive in vitro and in vivo), 17 true negative comparisons (resistant both in vitro and in vivo) and 3 false positive comparisons (sensitive in vitro, resistant in vivo). A result was obtained in 38 of 50 samples received, comprising 16 of 18 chronic lymphocytic leukaemias, 11 of 20 acute lymphoblastic leukaemias, 5 of 5 acute myeloid leukaemias and 6 of 7 myelomas. The assay appears to show considerable promise as a tumour chemosensitivity test and warrants wider investigations. PMID- 2580769 TI - Chemotherapy as definitive treatment of stage I-II large cell and diffuse mixed lymphomas. AB - Combination chemotherapy with adriamycin-containing regimens is effective in the management of advanced lymphomas. In view of this, we treated 43 patients with clinical stage I-II large cell or diffuse mixed lymphoma with chemotherapy. Routine staging laparotomies were not done and radiotherapy was not used in these patients. The CR rate for the combined stage I-II presentations is 90%. Of 11 patients with stage I presentations, only one has relapsed (at 64 months), and he expired 11 months after the recurrence. Of the 28 patients with stage II presentations who achieved a CR, seven have relapsed but three of these have achieved a second CR and remain in remission. Late relapses were common in this group of stage I-II presentations. Four of eight relapses occurring in patients who achieved disease-free status took place greater than 24 months after initiation of therapy. Chemotherapy alone appears to be adequate for treatment of stage I large cell lymphoma, although larger numbers of patients might be required to definitely make this conclusion. Close to 2/3 of patients with stage II presentations appear to have been cured with the use of chemotherapy alone. The failures occurred mostly in those with bulky disease. It is possible that radiotherapy given after chemotherapy could consolidate these bulky areas of disease and thus prevent local relapses. PMID- 2580770 TI - Cytokinetic study on the effects of N4-behenoyl-1-beta-D-arabinofuranosylcytosine on murine leukemic cells L 1210: a comparison with the effects of 1-beta-D arabinofuranosylcytosine. AB - The effects of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC) on the cell cycle of murine leukemic cells (L 1210 cells) were compared with those of 1-beta D-arabinofuranosylcytosine (ara-C), known to be effective for acute leukemia. In a cytokinetic study, a combination of Feulgen microcytofluorometry and tritiated thymidine autoradiography (3H-TdR ARG) was used to measure DNA content and to determine DNA synthesis simultaneously in a single cell. Administration of 200 mg/kg of BH-AC significantly prolonged the survival time of mice bearing L 1210. In addition, the cells in the G1 + S1 phases increased with time, accounting for 94.4 per cent of all cells measured at 48 h after the administration, compared to 73.7 per cent before administration. On the other hand, following the administration of 86 mg/kg of ara-C (equivalent to 200 mg/kg of BH-AC), the percentage of cells in the S1 + S2 phases increased maximally to 75.9 per cent at 18 h. Cytokinetic studies further showed that BH-AC administration blocks DNA synthesis of the cells in the S-phase for a longer period than does ara-C. These results suggest that the prolonged inhibition by BH-AC on DNA synthesis allows cells to accumulate in the S-phase to a greater degree. PMID- 2580771 TI - PGP 9.5, a new marker for human neuroendocrine tumours. AB - PGP 9.5 is a soluble protein isolated from brain and is a general marker for neuronal and neuroendocrine tissue. Its function is not known. Until now neurone specific enolase (NSE) has been the only general marker for the paracrine system and tumours derived from it. Seventy-four neuroendocrine tumours, 17 melanocytic naevi, 51 melanomas and four granular tumours were stained immunohistochemically for PGP 9.5 and NSE. A variety of pulmonary and non-neuroendocrine tumours were also stained. Two so-called goblet cell carcinoids of the appendix were included in the series. Using NSE 59/74 neuroendocrine tumours were positive and 58/74 stained for PGP 9.5. In combination 63/74 of these tumours were positive for either NSE or PGP 9.5 or both. Staining for PGP 9.5 was better for demonstration of nerves in routinely processed material than was staining for NSE. Twenty-one out of 43 primary melanomas stained for PGP 9.5 and 36 showed staining for NSE. Only two of eight metastatic melanomas melanocytic stained for PGP 9.5 while seven of these eight stained for NSE. Six of 17 melanocytic naevi stained for PGP 9.5 and five stained for NSE. All four granular cell tumours stained for PGP 9.5 and NSE. Both "goblet cell carcinoids' of the appendix were negative for NSE and PGP 9.5. Fifteen out of 32 pulmonary cancers showed staining for either marker and no non endocrine tumour showed any specific staining. Staining for PGP 9.5 is a valuable additional probe in the exploration of the paracrine system and the diagnosis of tumours arising from it. PMID- 2580772 TI - A study on the relationship between solid cell nests and mucoepidermoid carcinoma of the thyroid. AB - Mucoepidermoid carcinoma of the thyroid (MECT) has been recently recognized as a pathological entity. The origin of MECT is unknown but the morphology of this tumour closely resembles features seen in the ultimobranchial body (UB) vestiges. Recent studies in man have shown strong evidence that the so-called solid cell nests (SCN) of the thyroid may correspond to the human UB vestiges. To investigate whether these vestiges are the site of origin of this tumour a comparative study on SCN and MECT was undertaken. One hundred autopsied thyroids cut at 2-3 mm intervals were studied for the presence of SCN. Histochemical (H & E, Alcian blue-PAS, Mayer mucicarmine) and immunohistochemical studies (calcitonin, epidermal keratin) were performed in SCN and four cases of MECT. Sixty percent of thyroids were found to have SCN. They were mainly composed of epidermoid-like cells arranged in solid structures or lining cystic cavities, tubular and follicular structures. Solid clusters usually showed lumina containing PAS-positive and mucin-positive cell debris. Mucin stains also revealed mucinous cells placed around lumina filled by mucosubstances. Characteristic PAS-positive rounded bodies were found filling lumina as well as within some apical epidermoid-like cells, mucinous cells and cell debris. An obvious transition between these cells, cell debris and mucosubstances filling the lumina was noticed; suggesting degenerative changes undergone by the epidermoid-like cell. MECT basically presented all histological and histochemical features shown by SCN, furthermore, calcitonin containing cells were observed in 54% of SCN, while a metastatic MECT also showed scattered C cells within solid islands. The presence of epidermal keratin in all SCN and MECT, together with the previous findings, are strong evidence that MECT could originate in the SCN or human UB vestiges. PMID- 2580773 TI - Polymorphism of Ag-stained nucleolus organizer regions in lymphocytes of patients with ovarian or breast adenocarcinoma. AB - The Ag-stainability of nucleolus organizer regions (NORs) in the acrocentric chromosomes identified by Q-banding was studied in 45 female patients with adenocarcinoma of the ovary or breast and in 45 healthy females. Significantly higher frequencies of Ag(+)NORs per individual (8.8 and 8.3; P less than 0.05), in the G group chromosomes (3.6 and 3.2; P less than 0.05), and in chromosome 21 (1.9 and 1.7; P less than 0.02) were found in patients, compared with controls. Despite the lack of significant differences in NORs between the groups of patients with ovarian and breast adenocarcinoma, the main difference between the patients and controls was due to the patients with adenocarcinoma of the ovary, where a significantly higher frequency of Ag(+)NORs was found in chromosomes 21 (P less than 0.01) and 13 (P less than 0.05). PMID- 2580774 TI - Alpha zero- and beta zero-thalassemia in a Thai family: unusually mild homozygous beta zero-thalassemia without alpha-globin gene deletion. AB - Alpha-globin genes were analyzed by the direct method of DNA mapping using alpha- and zeta-globin specific probes in a Thai family in which the proposita was an unusually mild beta zero-thalassemia homozygote. alpha zero-Thalassemia was found to be segregating in the family, inherited from the proposita's father by one of her younger sisters. However, alpha zero-thalassemia was not detected by this DNA mapping in the proposita. The mild homozygous beta zero-thalassemia in this family may result from interactions of a non-deletion alpha-thalassemia, a gene responsible for high proteolytic activity permitting more balanced globin-chain levels, or from an unusually active hemoglobin F production in the proposita. PMID- 2580775 TI - Kinetics of inhibition of mitogen-induced proliferation of human lymphocytes by alpha 2-macroglobulin in serum-free medium. AB - The effect of alpha 2-macroglobulin (alpha 2M) on the ability of human lymphocytes to proliferate in response to stimuli by 3 mitogens, concanavalin A, phytohaemagglutinin and pokeweed mitogen was investigated in in vitro lymphocyte cultures in serum-free medium. The following experiments were performed: 1. lymphocytes were treated with alpha 2M prior to stimulation with the mitogens; 2. alpha 2M and mitogens were added simultaneously to the lymphocyte cultures; and 3. alpha 2M was added to the lymphocyte cultures after they were stimulated with the mitogens. In all cases, alpha 2M was found to inhibit mitogen induced proliferation of the lymphocytes as evaluated by (6-3H)-thymidine uptake of the cells. The mechanisms involved in the inhibition of lymphocyte proliferation by alpha 2M are discussed. PMID- 2580776 TI - Self reactive delayed type hypersensitivity (DTH) induced in mice by syngeneic lymphoblasts. AB - Normal and x-irradiated A mice injected with syngeneic concanavalin A (Con A) induced lymphoblasts revealed after challenge with syngeneic lipopolysaccharide (LPS)-induced lymphoblasts delayed type hypersensitivity (DTH) measured both by footpad swelling and by 125IudR accumulation. Mice injected with allogeneic Con A induced lymphoblasts and challenged with syngeneic LPS-induced lymphoblasts or vice versa, also generated an appreciable DTH response. In contrast, Con A induced blast cells of human origin (xenogeneic cells) generated a considerably less effective DTH. The DTH response was more profound and consistent in x irradiated mice, suggesting that irradiation sensitive cells control this response. The syngeneic DTH response was efficiently transferred to naive recipients with Thy-1+, nylon wool passed cells. The establishment of the DTH activity was associated with the lymphoblasts own (differentiation?) antigens and not with contaminants attached to the cells, such as Con A or fetal calf serum. The results were compared with similar results reported by other groups and the biological significance of all findings was evaluated. PMID- 2580778 TI - Calculation of monoclonal antibody affinity constants directly from antibody dilution curves. PMID- 2580779 TI - Human monoclonal antibodies produced by Epstein-Barr virus transformed cell lines bind protein A. AB - Epstein-Barr virus (EBV) is a polyclonal T-independent activator of viral receptor positive human B lymphocytes. Lymphocytes infected in vitro with the virus are transformed into immortalized cell lines [Nilsson, K, and Klein, G. (1982) Adv. Cancer Res. 37, 319]. In this way human cell lines that secrete specific IgM, IgG and IgA monoclonal antibodies are established. Protein A is also a polyclonal T-independent B cell activator [Langone, J. J. (1982) Adv. Immunol. 32, 157], the targets of which are surface immunoglobulin and C3d receptor positive cells, as are the targets of EBV. We found that almost all (16 out of 17) of the specific monoclonal antibodies (IgM, IgG and IgA) produced in vitro by EBV cell lines bind protein A. Unlike these in vitro produced antibodies, a substantial fraction of the immunoglobulins in human serum does not bind protein A. Thus, those plasma cells which in vivo secrete protein A nonbinding immunoglobulins originate from precursors of B cell that were EBV noninfective. Alternatively, during in vivo B differentiation some immunoglobulins undergo a change from protein A binding to protein A nonbinding molecules. PMID- 2580777 TI - Studies on the mechanism whereby cyclosporin A inhibits T-lymphocyte activation. AB - The immunosuppressive drug Cyclosporin A (CyA) inhibited the ConA-induced DNA synthesis in C57B1/6 spleen cells at a concentration of 40 ng/ml totally; this inhibition could not be overcome by the addition of highly purified interleukin 1. ConA-induced RNA synthesis was also inhibited by concentrations of 40 or 200 ng/ml CyA, although total inhibition could not be achieved. In contrast, lipopolysaccharide-induced proliferation could not be inhibited. CyA at a concentration of 40 ng/ml also inhibited the ConA-induced production of interleukin-2 by mouse spleen cells, this inhibition was not due to a toxic mechanism. On the contrary, the proliferative response of T cell blasts from a long-term T cell line (M2) to interleukin-2 containing supernatants was not inhibited by concentrations of 40 or 200 ng/ml CyA; only at 20-100-fold higher concentrations partial inhibition could be observed. One of the earliest events in the course of lymphocyte activation, the enhanced incorporation of unsaturated fatty acids into the lymphocyte plasma membranes; was also inhibited by concentrations of CyA, which abrogated the ConA-induced DNA synthesis. The inhibition of the enhanced incorporation of 14C-oleic acid and 14C-linoleic acid, which are incorporated by the membrane-bound lysolecithin-acyltransferase, thus suggests a molecular site of action for CyA. PMID- 2580780 TI - Autoimmune T-lymphocytes with specificity for pancreatic islet antigens. AB - The question is still unresolved whether in insulin-dependent (type I) diabetes T lymphocytes mediate an autoimmune response towards pancreatic islets. We now present direct evidence in an animal model for autoimmune T-lymphocytes with specificity for islet antigens. Mice of strain C57BL/6 were immunized repeatedly with islet homogenates. Lymphocytes isolated from draining lymph nodes and the spleen show a specific proliferative response when challenged with mouse rat or islet antigens but do not respond to liver or spleen antigens. Islet antigen specific lymphoblasts have been maintained by in vitro culture for several weeks in the presence of T-cell growth factor containing medium. PMID- 2580781 TI - Epitopic difference among rat thyroglobulins. AB - Epitopes on thyroglobulin (Tg) were examined using mouse monoclonal antibodies (mAbs). Two out of 6 mAbs indicated a remarkable difference in binding to three rat Tgs. Namely, they bound to one Tg as well as immunized Tg but could not bind to another at all. They could hardly bind to the third Tg. Another mAb was similar, to some extent, in binding to three rat Tgs as described above, although three other mAbs bound almost equally to three rat Tgs. Since competitive binding inhibition by Tgs supported the result of the binding study, the epitopic difference on rat Tgs was confirmed. Furthermore, competitive binding inhibition by unlabeled mAbs revealed that six mAbs recognized different epitopes individually. Therefore, there were at least two unique epitopes located on one rat Tg but not located on another. The relation between unique epitopes and thyroiditis in the rats used in the present study is also discussed. PMID- 2580782 TI - Specificity study of PPD-reactive human T cell line and clones. AB - Peripheral blood mononuclear cells from a PPD-sensitive human subject, in vitro stimulated by PPD, could be maintained for several weeks in interleukin 2 containing medium, with regular reactivation with PPD and irradiated autologous mononuclear cells used as antigen-presenting cells. The proliferative response of this T cell PPD-reactive bulk culture could be stimulated to proliferate by PPD itself as well as by BCG and other mycobacteria. This T cell line comprised a majority of T cells expressing the OKT4+, OKT8- phenotype, and a minor proportion of T cells (8%) showing the OKT4-, OKT8+ phenotype. Two PPD-reactive clones, both OKT4+, were obtained from this line by the limiting dilution technique. Clone C9 was found to be highly specific of PPD and BCG, whereas clone A9 could be activated by four other species of mycobacteria. These data demonstrate the existence of species-specific and cross-reactive epitopes within PPD and prompt for the use of PPD-reactive clones as a tool for identification and purification of the molecules bearing these epitopes. PMID- 2580783 TI - Allospecific T cell recognition of HLA-A2 antigens: evidence for group-specific and subgroup-specific epitopes. AB - Interleukin 2-dependent alloreactive cytotoxic T cell lines, with activity predominantly directed against the HLA-A2 antigen, have been generated in vitro by stimulating blood mononuclear cells from donors nonimmune to the Epstein-Barr (EB) virus with appropriate numbers of EB virus-transformed B cells from A2 homozygous individuals. Such effector cells were tested against a panel of EB virus-transformed target cell lines all expressing the serologically defined A2 antigen but typed into "common A2" and "variant A2" subgroups on the basis of their recognition by A2-restricted EB virus-specific cytotoxic T cells. "Variant A2" responder cells cocultivated with "common A2"-bearing stimulators gave rise to effector T cell lines which recognized only the "common A2"-bearing subgroup of targets. By contrast, responder cells from A2-negative donors stimulated with "common A2"-bearing cells produced effector T cell lines in which the strong lysis of "common A2"-bearing targets was accompanied by a lower, but still significant, lysis directed against all targets within the "variant A2" subgroup. In both cases, lysis of the target cells was blocked equally well by the anti-A2 specific monoclonal antibody MA2.1 as by the monoclonal antibody W6/32 specific for HLA-A, -B, and -C determinants. This suggests that HLA-A2 molecules possess at least two distinct sets of epitopes capable of inducing alloreactive T cell cytotoxicity: first, epitopes probably associated with T cell-restricting sites, which generate subgroup-specific responses, and second, epitopes shared by all A2 molecules, and perhaps associated with serologically defined sites, which generate "pan A2" group-specific responses. PMID- 2580784 TI - Correlation of Qa-1 determinants defined by antisera and by cytotoxic T lymphocytes. AB - Cytotoxic T lymphocytes (CTL) activated in H-2 identical, Qa-1 disparate mixed leukocyte cultures recognize H-2-nonrestricted target antigens indistinguishable by strain or tissue distribution from serologically defined Qa-1 antigens. Cloned Qa-1-specific CTL define determinants encoded by four Qa-1 genotypes; we used anti-Qa-1 sera in antibody blocking experiments to determine if these determinants reside on molecules recognized by Qa-1-specific antibodies. Antisera containing Qa-1.1-specific and TL-specific antibodies blocked recognition of two CTL-defined determinants associated with Qa-1a. Although both Qa-1 and TL molecules are expressed on activated T cells from appropriate strains, our studies indicated that the CTL recognized Qa-1, not TL. In addition, anti-Qa-1.2 serum inhibited CTL recognition of Qa-1b- and Qa-1c-encoded determinants. Qa-1d target cells are unique in that they express determinants recognized by anti-Qa 1a CTL and by anti-Qa-1b CTL. Killing of Qa-1d targets by anti-Qa-1a CTL was not inhibited by anti-Qa-1.1 serum, but was partially inhibited by anti-Qa-1.2 serum. Cytotoxicity of Qa-1d cells by one anti-Qa-1b CTL clone was inhibited by both anti-Qa-1.2 and anti-Qa-1.1 sera, indicating close association of both serological determinants with the determinants recognized by the CTL. Thus, all of the CTL-defined Qa-1 determinants resided on molecules recognized by Qa-1 specific antibodies, but anti-Qa-1a CTL and Qa-1.1-specific antibodies did not have identical specificities. PMID- 2580785 TI - Selective destruction by formaldehyde fixation of an H-2Kb serological determinant involving lysine 89 without loss of T-cell reactivity. AB - In preparation for functional analyses, a study of the binding of H-2Kb-specific monoclonal antibodies (mAb) to formaldehyde (FOR)-fixed H-2b spleen or tumor cells revealed that three of nine mAb tested had lost reactivity with the FOR fixed cells, whereas the reactivity of the other mAb generally did not diminish. Comparison of the reactivity of these mAb on untreated H-2Kbm mutant cells and on FOR-treated H-2Kb cells suggests that for three mAb the total loss of reactivity on the latter could be a consequence of the alteration by FOR of lysine 89, which is substituted by alanine in mutant bm3. H-2Kb-specific alloreactive polyclonal or monoclonal CTL, all of which had retained reactivity with bm3 target cells, had also retained reactivity with FOR-fixed H-2b cells as indicated by cold target inhibition studies. The H-2Kb-specific CTL were probably reactive with "conformational" determinants of H-2Kb, which are dependent on the integrity of both the alpha 1 and the alpha 2 domains of the H-2Kb molecule. Results are compatible with FOR treatment selectively affecting a serological determinant in the alpha 1 domain without affecting conformational-type CTL determinants. PMID- 2580786 TI - Construction and comparison of recombinant plasmids encoding type 1 fimbriae of members of the family Enterobacteriaceae. AB - The genes encoding type 1 fimbriae of Salmonella typhimurium, Enterobacter cloacae, and Serratia marcescens were cloned in Escherichia coli. All transformants possessing recombinant plasmids were shown to be fimbriate and demonstrated mannose-sensitive hemagglutinating activity. A comparison of the physical maps of these plasmids revealed little similarity among them, although plasmids encoding type 1 fimbriae of Escherichia coli and Klebsiella pneumoniae appeared similar with respect to restriction enzyme sites. The fimbrial gene cluster ranged in size from 5.5 to 9.0 kilobase pairs as determined by transposon mutagenesis. Plasmid-containing E. coli strains were shown to produce species specific fimbrial antigens with little or no cross-reactivity between genera. Therefore, it was presumed that each plasmid contained the gene encoding the fimbrial subunit. Complementation was not detected between nonfimbriate insertion mutants of different species but was seen with mutants of the same species. PMID- 2580788 TI - Structural and antigenic analysis of meningococcal piliation. AB - Pilin with an Mr of 16,500 was purified to homogeneity from Neisseria meningitidis SP3428. Procedures which provided useful separation during purification included high-pressure liquid chromatography with a TSK size exclusion column, Sephacryl S-200 column chromatography, ion-exchange chromatography with SP-Sephadex, and preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis. The amino acid composition of this pilin was similar to that previously reported for this species. The sequence of N-terminal 51 amino acids was also determined. The protein lacked a modified phenylalanine at the amino terminus and displayed six residues which were different from Neisseria gonorrhoeae in that region of the molecule determined to be the lectin binding domain. Monoclonal antibody raised to this pilin was employed, along with a monoclonal antibody to an epitope common to all gonococcal pilins, to analyze the intra- and interstrain heterogeneity of meningococcal piliation. The results indicate that N. meningitidis displays considerable intra- and interstrain heterogeneity with respect to both pilus subunit size and antigenicity. The Mr of subunits ranged from 13,000 to 20,000. PMID- 2580787 TI - Adherence of Entamoeba histolytica trophozoites to rat and human colonic mucosa. AB - We studied the adherence of [3H]thymidine-labeled axenic Entamoeba histolytica (strain HM1-IMSS) to in vitro preparations of rat and human colonic mucosa. Studies were performed with fixed or unfixed rat colonic mucosa, unfixed rat mucosa exposed to trypsin, unfixed rat submucosa, and fixed human colonic mucosa. Twenty percent of the amebae adhered to fixed rat colonic mucosa; adherence was specifically inhibited by N-acetyl-D-galactosamine (GalNAc), galactose, and asialofetuin. The adherence of amebae to fixed human colonic mucosa was also GalNAc inhibitable. Greater adherence was found with unfixed rat colonic mucosa (40.9%) and was not GalNAc inhibitable unless the tissue was first exposed to trypsin. However, GalNAc did inhibit the adherence of amebae to unfixed rat submucosa. Glutaraldehyde fixation of amebae inactivates known amebic adhesion proteins; there was a markedly decreased adherence of fixed amebae to trypsin exposed mucosa or fixed rat colonic mucosa. However, fixed or viable amebae had equal levels of adherence to unfixed rat colonic mucosa, suggesting the presence of a host adhesion protein that binds to receptors on amebae. Human (10%) and rabbit (5%) immune sera reduced the adherence of viable amebae to fixed rat colonic mucosa. We concluded that the GalNAc-inhibitable adhesion protein on the surface of E. histolytica trophozoites mediated adherence to fixed rat mucosa, fixed human colonic mucosa, trypsin-exposed unfixed rat mucosa, and unfixed rat submucosa. The surface of unfixed rat colonic mucosa contained a glutaraldehyde- and trypsin-sensitive host adhesion protein, perhaps in the overlying mucus blanket, which bound viable or fixed E. histolytica trophozoites. PMID- 2580789 TI - Partial amino acid sequence and molecular cloning of the encoding gene for the major outer membrane protein of Chlamydia trachomatis. AB - The first 25 N-terminal amino acids of the major outer membrane protein of Chlamydia trachomatis serovar L2 were determined. The amino acid sequence was used to construct an oligonucleotide probe specific for the major outer membrane protein gene. Using this oligonucleotide as a hybridization major outer membrane protein gene. Using this oligonucleotide as a hybridization probe, we discovered one recombinant clone that produced a 15-kilodalton polypeptide which reacted with a monoclonal antibody directed against the major outer membrane protein type specific epitope. In a separate set of experiments, we uncovered another recombinant clone that produced a 51-kilodalton polypeptide which was reactive with an anti-major outer membrane protein subspecies-specific monoclonal antibody. The expression of these recombinant DNA plasmids in Escherichia coli is discussed. PMID- 2580790 TI - Levels of salivary lysozyme, lactoperoxidase, and lactoferrin in diabetic hamsters. AB - In an attempt to clarify the mechanism(s) of increased susceptibility to oral infection in diabetics, we examined the levels of salivary antibacterial factors, including lysozyme, lactoperoxidase, and lactoferrin, in diabetic hamsters whose condition was induced with streptozotocin. Saliva was collected from these hamsters periodically for 19 weeks after the administration of streptozotocin. Diabetes persisted with significant hyperglycemia throughout the experiment after a single injection of streptozotocin. There was no significant difference between groups in the amount of saliva secreted. In diabetic hamsters, lysozyme activity decreased by 56% and lactoperoxidase activity decreased by 53% compared with the control hamsters 19 weeks after the administration of streptozotocin. There was no significant difference between groups in the amount of salivary lactoferrin. However, the ratio of lactoferrin to total protein increased to approximately double the amount of that of the control hamsters. Insulin treatment had a significant effect on lysozyme and lactoperoxidase activity, recovering 73 and 74% those of the controls, respectively, and the ratio of lactoferrin to total salivary protein reverted to normal values. Growth inhibition of Lactobacillus plantarum ATCC 8014 with whole saliva and amylase activity significantly decreased in diabetic hamsters. The position of each protein band of whole saliva on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was almost the same for control and diabetic hamsters; however, there was some variability in band intensity. PMID- 2580791 TI - Immunoresponses to Neisseria meningitidis epitopes: primary versus secondary antiphosphorylcholine responses. AB - Specific antiphosphorylcholine immune responses were found to be elicited by different Neisseria meningitidis group B M986 preparations. Our results suggest the functional presence of phosphorylcholine in the bacteria. The immune responses, mostly immunoglobulin M, were measured with a plaque-forming cell assay. The secondary phosphorylcholine-specific immune response induced by intact meningococci was significantly lower than the primary phosphorylcholine-specific immune response induced by the same antigens. This suppression is priming time dependent and does not represent an early switching to the expression of other classes of immunoglobulins. PMID- 2580792 TI - Serotypes, hemolysin production, and receptor recognition of Escherichia coli strains associated with neonatal sepsis and meningitis. AB - Sixty-three Escherichia coli strains isolated from neonatal sepsis or meningitis were studied and compared with previous data on fecal or urinary pyelonephritis associated isolates from children. Characteristics significantly associated with neonatal infection were capsular type K1 (54%), O group 18 (27%), rough-type lipopolysaccharide together with K1 capsule (19%), and S fimbriae (29%). Within the neonatal infection group, the K1 capsule and rough lipopolysaccharide were most common among the youngest infants (0 to 21 days old) and in meningitis. Hemolysin production, P fimbriae, and X adhesions (adhesions not identifiable as type 1, P, or S) were significantly more common in the two materials from infections as compared with the fecal isolates. One large clone of 11 strains (O18:K1:H7, with both type 1 and S fimbriae) and three smaller ones (O7:K1:H1 and O6:K2:H1, both with type 1 and P fimbriae and X adhesions; and R:K1:H33 with no adhesions) were identified among the strains from neonatal infections. Only O6:K2:H1 strains were also common among the strains from pyelonephritis. PMID- 2580793 TI - Antigenic heterogeneity of lipopolysaccharides from Campylobacter jejuni and Campylobacter fetus. AB - The lipopolysaccharide (LPS) structure of Campylobacter spp. can be visualized with polyacrylamide gel electrophoresis by examining proteinase K-treated whole cell lysates. Polyacrylamide gel electrophoresis LPS profiles of C. jejuni strains are rough type with low concentrations of low-molecular-weight polysaccharide side chains, serum-resistant C. fetus strains have smooth-type LPS, and serum-sensitive C. fetus strains have rough-type LPS. We electroblotted the proteinase K-treated whole cell lysates of 17 C. jejuni and 9 C. fetus strains from polyacrylamide gel electrophoresis to nitrocellulose paper to examine antigenicity to immune rabbit sera. There was virtually no antigenic cross-reactivity of C. jejuni and C. fetus LPS. Among C. jejuni strains, core LPS structures were cross-reactive, but the O-polysaccharide side chains were best recognized by homologous antisera. Antisera to several serum-resistant C. fetus strains recognized only the polysaccharide side-chain regions of serum-resistant strains and no part of the LPS from the sensitive strain. Antiserum raised against a serum-sensitive C. fetus strain but not homologous antisera recognized the core region of the LPS of the serum-resistant C. fetus strains. These findings suggest that core LPS antigens are widely shared within C. fetus subsp. fetus strains but that in the serum-resistant strains this core region is not surface exposed and therefore not immunogenic to rabbits infected with whole cells. PMID- 2580794 TI - Effect of proteolytic cleavage of surface-exposed proteins on infectivity of Chlamydia trachomatis. AB - The proteolytic cleavage of Chlamydia trachomatis LGV-434 surface proteins and resultant effects on infectivity and association with cultured human epithelial (HeLa) cells have been examined. Of several proteases examined, trypsin, chymotrypsin, and thermolysin extensively cleaved the chlamydial major outer membrane protein (MOMP). Two proteases, trypsin and thermolysin, cleaved the MOMP to the extent that monomeric MOMP was not detectable by immunoblotting with monospecific polyclonal antibodies. In the case of thermolysin, not even antigenic fragments were detected. Surprisingly, infectivity toward HeLa cells was not diminished. In addition, the association of intrinsically 14C radiolabeled elementary bodies (EBs) with HeLa cells or their dissociation by proteinase K was not measurably affected by prior trypsinization of the EBs. Trypsinization of lactoperoxidase surface-iodinated elementary bodies demonstrated that most of the 125I-labeled surface proteins were cleaved. In all cases, however, a number of proteolytic cleavage fragments remained associated with the EB surface after surface proteolysis. When trypsinized EBs were electrophoresed under nonreducing conditions and immunoblotted with either polyclonal or type-specific monoclonal MOMP antibodies, MOMP was found in a large oligomeric form that failed to enter the polyacrylamide stacking gel. Additionally, trypsinized viable EBs bound radioiodinated type-specific MOMP monoclonal antibody as efficiently as did the control nontrypsinized organisms. Taken together, the findings indicate that although the MOMP is highly susceptible to surface proteolysis, the supramolecular structure of the protein on the EB surface is apparently maintained by disulfide interactions. Thus, if surface-exposed chlamydial proteins are involved in the initial interaction of chlamydiae with eucaryotic cells, the functional domains of these proteins which mediate this interaction must be resistant to proteolysis and remain associated with the EB surface. PMID- 2580795 TI - Antigenic properties of Chlamydia trachomatis lipopolysaccharide. AB - The antigenic properties of the lipopolysaccharide (LPS) of Chlamydia trachomatis L2 were investigated. By means of passive hemolysis, passive hemolysis inhibition, and absorption experiments, it was shown that antiserum raised against chlamydial elementary bodies contained at least two different antibody specificities which reacted with different antigenic determinants of chlamydial LPS. One of these antibodies cross-reacted with enterobacterial Re LPS, recognizing a structure which is shared by both LPSs, whereas the reactivity of the second antibody was restricted to chlamydial LPS. The former antibody could be absorbed with Salmonella minnesota Re LPS, whereas the latter was not affected by this absorption. Therefore, chlamydial LPS possesses two distinct antigenic determinants, one of which is C. trachomatis specific, the other of which is responsible for the cross-reactivity with enterobacterial Re-type LPS. Both antigenic determinants were destroyed during mild acid-catalyzed hydrolysis. It was further shown that free chlamydial lipid A exhibits antigenicity that cross reacts with free enterobacterial lipid A. This antigenicity, however, as in enterobacterial LPS, is present in a cryptic form, i.e., it is unmasked only after acid hydrolysis of LPS. PMID- 2580796 TI - Antigenic mimicry of mammalian intermediate filaments by mycoplasmas. AB - A murine monoclonal antibody raised against Mycoplasma hyorhinis specifically reacted by indirect immunofluorescence with mammalian intermediate filaments. The antibody recognized a related epitope on a 74,000-molecular-weight protein of M. hyorhinis and on components of similar size from other pathogenic mycoplasmas. This defines a shared antigenic structure of interest in autoantibody development during mycoplasmal diseases. PMID- 2580797 TI - Binding activity of a murine anti-lipid A monoclonal antibody. AB - In this report we briefly describe an immunoglobulin G3 monoclonal antibody, 2G6/1H11, which binds purified lipid A from Salmonella minnesota and a lipid A precursor molecule derived from Salmonella typhimurium. 2G6/1H11 does not bind well to purified whole S. typhimurium lipopolysaccharide (LPS), S. minnesota LPS, LPS preparations from a series of S. minnesota rough mutants, or intact S. typhimurium bacteria. Thus, there are antigenic determinants in purified lipid A which are not exposed when lipid A is presented as part of the whole LPS molecule or intact bacteria. PMID- 2580798 TI - Results of a World Health Organization-sponsored workshop on monoclonal antibodies to Mycobacterium leprae. PMID- 2580799 TI - A dual expression of cytokeratin and neurofilaments in bronchial carcinoid cells. AB - Intermediate filaments (IF) are ubiquitous cytoplasmic structures which, by virtue of their cell- and tissue-type-specific characteristics, are widely used as markers of tissue derivation and as differential diagnostic aids in surgical pathology. In contradistinction to other IFs, vimentin filaments, characteristic of mesenchymal cells, may be co-expressed with other cell-type specific IFs- cytokeratin filaments, desmin filaments, glial filaments and neurofilaments--in some tumor cells, embryonic cells, and cells in vitro. In this study we describe a novel type of IF co-expression which does not involve vimentin-filaments, viz. the presence of both cytokeratin filaments and neurofilaments in human bronchial carcinoid tumor cells. PMID- 2580800 TI - Cell surface antigens of human trophoblast and choriocarcinoma defined by monoclonal antibodies. AB - Six distinct cell surface antigens of human trophoblast and choriocarcinoma were defined with MAbs. The distribution of the antigens was determined by MHA assays on 150 tumor cell lines and normal cell cultures and by immunofluorescence tests with a wide range of normal adult and fetal tissues and a tumor panel. Antigen LK26 is expressed on all cultured choriocarcinoma, teratocarcinoma and renal cancer lines but is absent from most cell lines derived from other tumor types and from cultures of normal kidney epithelium and fibroblasts. LK26 expression in normal tissues is restricted to the trophoblast. No other adult or fetal tissue was found to express the antigen, but choriocarcinoma and teratocarcinoma tissues were LK26+. SV19 is expressed on cultured choriocarcinomas and teratocarcinomas and on subsets of breast and colon cancer lines, but not on 120 additional cultures tested. In tissues, SV19 is detected in normal placenta, mammary gland and colon epithelium as well as in tumors of breast, colon and lung. Two antibodies, AbSV63 and AbK8, react with PLAP and AbSV63 also reacts with the intestinal form of the enzyme. AbLK24 defines a heat-stable determinant present on choriocarcinoma and breast cancer cell lines but absent from most other cultured cells. It is expressed on a small range of normal and malignant epithelial tissues, including normal trophoblast, normal breast epithelium and urothelium and tumors derived from these tissues. One antigen, K66, showed a wide distribution on cultured epithelial cells but was not found in any normal or malignant tissue. Finally, S4, a previously described marker of normal and malignant kidney epithelial cells, was also expressed on the choriocarcinoma cell lines. Four of the antigens are glycoproteins that could be immunoprecipitated from radiolabelled extracts of choriocarcinoma cells: LK26 (Mr 35,000), SV19 (Mr 40,000), PLAP (Mr 68,000) and S4 (Mr 160,000). The highly restricted distribution of LK26, SV19, S4, and PLAP in normal tissues and their expression in tumors make these antigens potential diagnostic markers of gestational choriocarcinoma and germ-cell tumors and, possibly, targets for immunotherapy. PMID- 2580801 TI - Muscarinic cholinergic receptors in pancreatic acinar carcinoma of rat. AB - The active enantiomer of tritiated quinuclidinyl benzilate (3H(-)QNB) was used as a ligand to evaluate the muscarinic receptors. The 3H(-)QNB binding characteristics of muscarinic cholinergic receptors obtained from normal and neoplastic tissues were studied to determine changes in receptor properties during neoplastic transformation. Saturable and stereospecific binding sites for 3H(-)QNB are present in homogenates of rat pancreatic adenocarcinoma. The proportions of high- and low-affinity agonist binding sites are similar for neoplastic and normal tissues. The density of muscarinic receptors is higher in neoplastic (200 femtomoles/mg protein) than in normal pancreatic homogenates (80 femtomoles/mg protein). The muscarinic binding sites of the neoplastic and fetal pancreas show similar KD values which are higher than those observed for normal pancreas. PMID- 2580803 TI - The effect of murine interferon-alpha/beta on an established Rauscher murine leukemia virus-induced erythroleukemia in BALB/c mice. AB - Rauscher murine leukemia virus (R-MuLV) induces a rapidly developing erythroleukemia in BALB/c mice. Previously, we have shown that mouse interferon alpha/beta (Mu IFN-alpha/beta) applied shortly after virus inoculation efficiently inhibits the leukemic process (Hekman et al., 1981). Here we describe the effect of Mu IFN-alpha/beta on an established leukemia. Varying doses of Mu IFN-alpha/beta were injected over 3 days, starting 8 to 12 days after virus inoculation. The effect of Mu IFN-alpha/beta on the leukemic process was monitored by measuring the spleen weight, reverse transcriptase activity in the serum and, in selected experiments, by microscopic examination of sections of the spleen using standard histological and immunological staining techniques. Depending on the spleen weight at the start of its application (maximal about 450 mg), Mu IFN-alpha/beta caused a dramatic reduction in the number of virus infected erythroleukemic cells in the spleen. Also, R-MuLV disappeared from the serum within 3 days. If Mu IFN-alpha/beta was injected into R-MuLV-infected mice with an already 10-fold enlarged spleen, it could only stop further development of leukemia. Results obtained with crude Mu IFN-alpha/beta preparations were confirmed with absolutely pure Mu IFN-beta. PMID- 2580802 TI - Transforming potential of a retrovirus isolated from lung carcinoma of sheep. AB - A retrovirus isolated from experimentally induced sheep lung carcinoma (SPCTV) was propagated in chronically infected Himalayan tahr ovarian cells and in normal sheep lung cells. Follow-up of infection of the cells with SPCTV showed the appearance of syncytium, plaque formation, partial recovery and the establishment of a chronic infection. Virus-associated reverse transcriptase activity in the medium fluctuated but remained at a constantly high level at the stage of chronic infection. Stages of type-C virus morphogenesis were demonstrated by electron microscopy. The viral genome was detected in both the nucleus and cytoplasm by in situ hybridization. Chronically infected cells formed colonies when plated in soft agar. Following subcutaneous inoculation of chronically infected cells (of fibroblast origin) into nude mice, lymphoid tumors developed at the site of inoculation and in vital organs. PMID- 2580804 TI - Effects of cortisone with and without heparin on angiogenesis induced by prostaglandin E1 and by S180 cells, and on growth of murine transplantable tumours. AB - Cortisone acetate, locally applied in sustained-release pellets, is effective in inhibiting angiogenesis induced by prostaglandin E1 in the rabbit cornea. The inhibitory effect of cortisone is not increased by addition of heparin. Similar results were obtained with angiogenesis induced by S180 cells. The effects of cortisone with and without heparin were also studied on 5 transplantable murine tumours: 3 variants of B16 melanoma, Lewis lung carcinoma and fibrosarcoma M4. The effect of cortisone in slowing the growth rate of tumours was modestly potentiated by heparin, but no regression of the tumour mass occurred. PMID- 2580807 TI - Familial odontogenic keratocysts. Report of 3 cases and review of Japanese dental literature. AB - Familial odontogenic keratocysts are described in this report. The Case 1 patient, who has 3 sisters, developed odontogenic keratocysts. The 2 younger sisters (Cases 2 and 3) also had odontogenic keratocysts, although the elder sister did not have any odontogenic cysts. The father of the patients had a history of removal of a jaw cyst, and the mother was found later to have malignant ameloblastoma. Besides the odontogenic keratocysts, the Case 1 patient had basal cell nevus, prominent frontal process, and ocular hypertelorism; the Case 2 patient had prominent frontal process; the Case 3 patient had prominent frontal process, ocular hypertelorism, and squint. All 3 sisters are suspected of being patients with the basal cell nevus syndrome. The Japanese dental literature concerning the basal cell nevus syndrome is reviewed. PMID- 2580806 TI - The release of morphine from the mast cells by 48/80 in morphine perfused dogs. AB - The aim of this study was to determine whether or not mast cells store or bind morphine. Injection of a potent mast cell depleter, compound 48/80 to dogs, 10 minutes after completion of a perfusion of 30 mg/kg of morphine produced a large concomitant increase of both morphine and histamine in blood samples drawn from the aorta. This increase is transient and statistically significant up to 1 minute following the injection of the drug. Morphine and histamine levels decrease rapidly as they reach the general circulation and are subjected to distribution. Injection of compound 48/80 one hour after the end of the morphine perfusion produces a less prominent increase in morphine and histamine levels. In both instances, subsequent doses of compound 48/80 failed to produce any increase in the levels of morphine or histamine. All these findings strongly indicate that in these dogs, the increase in morphine levels following 48/80 injection is caused by a release of morphine, bound or stored in the mast cells of the lungs, during the course of the perfusion. PMID- 2580805 TI - Torsade des pointes and aprindine. AB - Aprindine was given orally to an 88-year-old patient with atrial fibrillation and ventricular premature depolarizations. The premature beats disappeared and sinus rhythm was restored on the third day of treatment. While on aprindine the QT interval was prolonged and the U wave became very prominent. The aprindine was stopped but 36 hr following the last oral dose, ventricular arrhythmia appeared with the characters of torsade des pointes. Three such episodes occurred within 24 hr. It is suggested that aprindine both eliminated the premature depolarizations and rendered the myocardium vulnerable by prolonging the QT interval. On discontinuing the medicament the premature beats reappeared while the myocardium was still vulnerable, so that torsade des pointes resulted. PMID- 2580808 TI - Prediction of strong antigenic determinant of seminalplasmin and ribonuclease from the amino acid sequence. AB - It has been reported earlier [Hopp, T.P. & Woods, K.R. (1981) Proc. Natl. Acad. Sci. US 78, 3824-3828] that the antigenic determinants of a protein can be delineated by examining the average local hydrophilicity values along the peptide chain. I have used this method to predict the strong antigenic determinants of two proteins, seminalplasmin and ribonuclease, of known sequence. In the former case, the N-terminal segment 1-14, and in the latter case the segments 27-38 and 80-86, are predicted to possess the antigenic determinants of the two proteins. Experimental verification already exists for the former case. PMID- 2580809 TI - Intravital fluorescence microscopy for the study of blood-brain-barrier function. AB - Vascular diameters and blood-brain-barrier (BBB) function were investigated in the parietal cortex of cats using an open skull window technique and intravital fluorescence microscopy. The cortical surface was superfused with artificial cerebrospinal fluid containing: bradykinin (BK), Na+-arachidonate (AA), or xanthine-oxidase (XO). Na+-fluorescein (MW: 376), fluorescein-isothiocyanate labelled (FITC) albumin (MW: 67 000), or FITC-dextran (MW: 19 400-62 000) were given intravenously as blood-brain-barrier indicators of different molecular size. In control experiments, the effect of continuous exposure of the preparation to the light source used for fluorescence excitation was studied. Dependent on the molecular size of the tracer and light intensity, continuous light exposure led to extravasation and disturbances of the microcirculation in small veins. When Na+-fluorescein was employed as barrier indicator at a magnification of X 40, at least 55 min of continuous illumination were required to induce extravasation. Brief, i.e. 0.5-15 s and discontinuous illumination for taking microphotographs amounting to less than 20 min in total did not induce extravasation in control experiments of 3.5 h. Opening of the blood-brain-barrier was studied during superfusion with a hypertonic solution (2000 mOsmol 1(-1)). The results obtained with bradykinin, Na+-arachidonate, or xanthine-oxidase indicate that opening of the barrier can occur independently from a corresponding vasodilating reaction. BK, or AA led to initial venular leakage as a result of an increase of selective, or global barrier permeability. On the other hand, XO did not induce extravasation, although cerebral vessels were markedly dilated. Taken together, the experimental model presented is suitable to simultaneously analyze dynamic changes of the permeability of cerebral vessels in-vivo with excellent spatial resolution and of the cerebral vasomotor behaviour under physiological and pathological conditions. PMID- 2580810 TI - The fine structure of tumor blood vessels. I. Participation of non-endothelial cells in tumor angiogenesis. AB - This report provides fine structural evidence that, dependent upon the malignancy, tumor as well as mesenchymal cells may participate actively in the neovascularization of experimental tumors grown in transparent tissue chambers implanted into skinfolds of syrian hamsters. Such non-endothelial cells may help to promote angiogenesis in two different ways: (1) They are incorporated into capillary sprouts thereby accelerating the growth rate of the latter independent of endothelial cell proliferation. (2) Extravascular cells (tumor and mesenchymal elements) become integrated in varying numbers into the linings of comparatively large blood-perfused vessels. This facilitates the rapid establishment and functional remodelling of the microvascular bed to adapt the microcirculation to the varying local demands of the growing tumor. If these results can be confirmed for other tumors, and if they are independent of the tumor's environment and the experimental protocol, then we will have to reconsider the significance of tumor angiogenesis as a realistic biological model from which general conclusions with regard to neovascularization in non-tumorous tissues may be drawn. PMID- 2580813 TI - Manganese chloride enhances natural cell-mediated immune effector cell function: effects on macrophages. AB - A single intramuscular injection of MnC12 in mice caused an increase in macrophage functional activity. Spleen cell antibody-dependent cell-mediated cytotoxicity against both chicken erythrocytes and P815 tumor cell targets was enhanced 24 h following a single injection of MnC12. Enhanced antibody-dependent cell-mediated cytotoxicity activity following MnC12 treatment was not associated with a change in spleen cellularities compared with saline-injected mice. Resident peritoneal macrophages from mice injected intramuscularly with MnC12 displayed enhanced phagocytic activity for chicken erythrocytes in the presence or absence of opsonizing antibody. Enhanced cytolytic activity against P815 mastocytoma target cells and enhanced cytostatic activity against MBL-2 lymphoma target cells was also observed for nonelicited resident peritoneal macrophages from mice injected intramuscularly with MnC12. There were no differences in the cellularity or relative number of adherent cells obtained from the peritoneal cavity of saline or MnC12-injected mice. These enhanced macrophage functions were associated with the induction of increased interferon levels in mice injected with MnC12. PMID- 2580811 TI - Additive cytotoxicity of adriamycin and a naturally occurring growth inhibitor extracted from bovine aorta. AB - A factor of nominal molecular weight 6K-10K Daltons, isolated from bovine aorta, has previously been shown to inhibit neovascularization and tumor growth in vivo and the growth of some tumor cells as well as endothelial cells in culture. This factor, termed A-10, was tested alone and in combination with Adriamycin against TA3Ha mammary adenocarcinoma cells in tissue culture. It was found to have cytotoxicity additive to that of Adriamycin in inhibiting the growth of these cells. In vitro and animal studies show that the sequence of Adriamycin----A-10 is superior to either agent alone in delaying the appearance of palpable tumors after subcutaneous injection of 10(5) pre-treated tumor cells in the tail of strain A mice. While the growth rate of the primary tumor was not affected by such treatment, survival was prolonged to a greater degree by the this sequence than by either of these agents used alone. A-10 treatment reduced the number of metastases to the adrenal gland but not to lung, liver, or lymph nodes. It did, however, reduce the size of metastases to para-aortic lymph nodes. PMID- 2580812 TI - Interferon induction in human leukocytes after in vitro exposure to cytomegalovirus or Epstein-Barr virus. AB - Interferon (IFN) was produced after exposure of human mononuclear leukocytes and bone marrow cells to infectious or noninfectious cytomegalovirus (CMV) in vitro. The IFN was generated mainly by non-B lymphocytes. Both alpha- and gamma-type IFN could be demonstrated. CMV antigens were usually not demonstrable in CMV-exposed leukocytes. Addition of anti-IFN antibodies did not induce CMV antigens. Thus, it seems that the endogenous production of IFN is not responsible for the difficulties in demonstrating CMV antigens after in vitro exposure of normal human leukocytes to CMV. Addition of Epstein-Barr virus (EBV) B95-8 to leukocytes induced the production of alpha-type IFN. Exogenously added IFN reduced the induction of EBV-determined nuclear antigen (EBNA). However, the presence of anti IFN antibodies in EBV-infected cultures did not increase the number of EBNA positive cells. PMID- 2580814 TI - Histochemical procedures for the simultaneous visualization of sialic acid, its side chain O-acyl variants and O-sulphate ester. PMID- 2580815 TI - Cytochemistry of the tubular aggregates found in hepatocytes of interferon treated suckling mice. AB - Administration of mouse interferon to neonatal mice induces the formation of tubular aggregates within hepatocytes. These aggregates are composed of networks of small tubules which are continuous with the granular endoplasmic reticulum. The tubules are bounded by trilaminar unit membranes and exhibit glucose-6 phosphatase activity. These features suggest that the tubular aggregate is an interferon-induced alteration of the endoplasmic reticulum. PMID- 2580816 TI - The use of antibodies to intermediate filament proteins in the differential diagnosis of lymphoma versus metastatic carcinoma. AB - Forty-nine cases encompassing 16 different types of malignant lymphoma were examined for their intermediate filament protein (IFP) type by indirect immunofluorescence microscopy of cryostat sections. In all cases, vimentin was shown to be the only IFP type detectable in these tumours. Lymphomas are negative for keratin and desmin, which are characteristic for benign and malignant epithelial or muscular tissues respectively. In addition, eighteen cases are described in which antibodies to intermediate filament proteins were used successfully to distinguish between lymphoma and metastatic carcinoma where differential diagnosis was difficult or impossible on the basis of routine histology. PMID- 2580819 TI - Radiotherapy for lung cancer. AB - The role of radiation therapy in the management of lung cancer was reviewed at a workshop held in Cambridge, England, in June 1984. It was concluded that there was a continuing role for radiation therapy in the primary management of small cell lung cancer, including the loco-regional treatment for patients with limited disease. Radical radiotherapy for patients with non-small cell carcinoma could be curative for a proportion of patients with limited disease. Careful planning and quality control was essential. Palliative radiotherapy provided useful treatment for many other patients. Other related aspects of treatment are also presented. PMID- 2580817 TI - Ultrastructural visualization of elastic fibres with a tannate--metal salt method. AB - A modification of the tannic acid-metal salt method was applied as an ultrastructural stain for elastin. Thin sections of glutaraldehyde-fixed, embedded rat aorta and rabbit elastic cartilage, with and without osmication, were examined. Raising the pH of the tannic acid solution from 2.7 to 9.0 progressively increased the electron-density of elastic fibres and collagen fibrils in osmicated and unosmicated specimens. The maximum tannic acid staining of elastic fibres was observed in the pH range 7.0-9.0. Collagen staining, although less intense than that of elastic fibres, was also greatest in this pH range. Elastic fibres in osmicated specimens demonstrated the strongest tannic acid staining with a minimal increase in density of collagen and cell nuclei when compared to the unosmicated specimens. Sequential treatments of osmicated specimens with tannic acid pH 7.0-9.0, and uranyl acetate, pH 4.1, enhanced the density of the elastin intensely, increased collagen staining moderately, but hardly increased the density of nuclei and microfibrils. In elastase-digested osmicated specimens, all tannic acid (pH 7.0)-uranyl acetate-reactive elastin was selectively removed. These results demonstrate that all the neutral and alkaline tannic acid-uranyl acetate methods can be used as a postembedment stain for elastin specimens fixed in glutaraldehyde and osmium tetroxide. PMID- 2580818 TI - An HLA class I specific monoclonal antibody that fails to bind to all HLA-A antigens. AB - A monoclonal antibody, MHM.5, specific for HLA class I antigens, bound to lymphocytes of all donors tested and was thought to bind to a monomorphic determinant. When the antibody was used to precipitate 35S methionine labeled HLA class I molecules from lymphoid cells, which were then isoelectric focused, it was found that the HLA-A1,A2 and A3 antigens were not precipitated. Similarly, MHM.5, which is IgG1, failed to block complement mediated lysis by alloantisera specific for HLA-A1, 2 and 3, and most other HLA-A antigens. HLA-Aw24, A25, and A32, and all other HLA-B and C typing reactions tested were blocked. Thus the antibody binds to an epitope that is lacking on most A antigens, but present on Aw24, A25, A32 and all B and C locus antigens. Comparison of the published amino acid sequences of HLA-A2, A3, Aw24, A28, Cw3, B7, and B40 suggests some possible sites for this epitope. PMID- 2580820 TI - Plasmapheresis as adjuvant therapy for autoimmune hemolytic anemia in two dogs. AB - Severe, acute, autoimmune hemolytic anemia in 2 dogs was treated, using prednisone, cyclophosphamide, plasmapheresis, and blood transfusion. In 1 case, splenectomy was performed successfully after plasmapheresis and blood transfusion. Antibody removal by means of plasmapheresis effected short-term stabilization to severe hemolysis in both dogs, but was suspected to have contributed to the death of 1 dog. PMID- 2580821 TI - A bridge to understanding: the transcendent function in the analyst. PMID- 2580822 TI - Effects of in vitro ronnel on metabolic activity in subcutaneous adipose tissue and skeletal muscle from steers. AB - Ronnel [0,0-dimethyl 0-(2,4,5-trichlorophenyl) phosphorothioate] is an organophosphate pesticide with growth-promoting properties. Experiments were conducted to determine effects of ronnel on oxidation of and fatty acid synthesis from acetate and glucose as indices of metabolic activity in subcutaneous adipose tissue and skeletal muscle from 6-, 12- and 18-mo-old steers. Ronnel depressed metabolic activity in adipose tissue from 6- and 12-mo-old steers without concomitantly decreasing metabolic activity in skeletal muscle. Production of CO2 and fatty acids from acetate and glucose in tissues from 18-mo-old steers was influenced less by ronnel than in tissues from younger steers. Interactions of ronnel with thyroxine or growth hormone on acetate oxidation and conversion to fatty acids in adipose tissue also were investigated. Thyroxine increased acetate oxidation and decreased fatty acid synthesis. Ronnel interfered with the metabolic effects of thyroxine. Growth hormone, with or without ronnel, did not affect metabolic activity of adipose tissue. Ronnel seemingly alters the partitioning of acetate and glucose between major metabolic processes in adipose tissue and skeletal muscle. PMID- 2580823 TI - Vasoactive effects of substance P on isolated rabbit pulmonary artery. AB - The vasoactive properties of substance P (SP) were studied in isolated rabbit pulmonary artery (PA) segments in vitro. In the absence of active base-line tone, noncumulative administration of SP (10(-11) to 10(-4) M) produced dose-dependent increases in PA tension. The peak isometric tension (Tmax) with SP was similar to the Tmax response to epinephrine; however, the doses of the agonist producing a threshold contraction and 25% of Tmax (ED25) were significantly lower for SP. In the presence of active base-line tone, induced by epinephrine or 5 hydroxytryptamine, SP produced transient PA relaxation which was directly related to the magnitude of the precontracted PA tension. Blockade of neurotransmission with tetrodotoxin (1 microgram/ml) and antagonists to alpha 1-adrenergic and histamine receptor binding had no effect on the contractile response to SP. On the other hand, PA contraction to an ED50 dose of SP was 1) inhibited by a mean of 33 +/- 10% (SE) following pretreatment with the cholinesterase inhibitor, neostigmine (10(-6) M) and 2) augmented by 52 +/- 21% with the cholinergic antagonist, atropine (10(-4) M). The latter also completely blocked the relaxation response to SP in precontracted PA. Similarly, removal of the PA endothelium also abolished the relaxation response to SP. In contrast, SP-induced contraction was markedly inhibited by the cyclooxygenase inhibitor, meclofenamate (1 microgram/ml), as well as the SP antagonist, D-Pro2, D-Trp7,9-SP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580824 TI - Ion selectivity of gram-negative bacterial porins. AB - Twelve different porins from the gram-negative bacteria Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, and Yersinia pestis were reconstituted into lipid bilayer membranes. Most of the porins, except outer membrane protein P, formed large, water-filled, ion-permeable channels with a single-channel conductance between 1.5 and 6 nS in 1 M KCl. The ions used for probing the pore structure had the same relative mobilities while moving through the porin pore as they did while moving in free solution. Thus the single-channel conductances of the individual porins could be used to estimate the effective channel diameters of these porins, yielding values ranging from 1.0 to 2.0 nm. Zero-current potential measurements in the presence of salt gradients across lipid bilayer membranes containing individual porins gave results that were consistent with the conclusions drawn from the single-channel experiments. For all porins except protein P, the channels exhibited a greater cation selectivity for less mobile anions and a greater anion selectivity for less mobile cations, which again indicated that the ions were moving inside the pores in a fashion similar to their movement in the aqueous phase. Three porins, PhoE and NmpC of E. coli and protein P of P. aeruginosa, formed anion-selective pores. PhoE and NmpC were only weakly anion selective, and their selectivity was dependent on the mobility of the ions. In contrast, cations were unable to enter the selectivity filter of the protein P channel. This resulted in a high anion selectivity for all salts tested in this study. The other porins examined, including all of the known constitutive porins of the four gram-negative bacteria studied, were cation selective with a 3- to 40-fold preference for K+ ions over Cl- ions. PMID- 2580825 TI - Dopamine stimulated increase of GTP levels in the rat retina. AB - Dopamine stimulates a 7-10-fold increase of GTP concentration in whole rat retina maintained in vitro. Half-maximal stimulation of GTP levels were obtained with 10(-6) M dopamine, and significant increases in GTP levels were seen with 10(-7) M dopamine. Intracellular GTP levels were significantly increased within 4 min after exposure to dopamine and maximal effects were reached within 30 min. Dopamine agonists, apomorphine and bromocriptine, also stimulate a 7-10-fold increase in GTP concentration, whereas other catecholamines (norepinephrine, epinephrine, and isoproterenol) were less potent. Several other neurotransmitters present in rat retina (gamma-aminobutyric acid, glycine, glutamine, and taurine) had no effect on GTP levels. Although dopamine also stimulates increases in cyclic AMP levels in the retina, dibutyryl cyclic AMP and 8-bromo-cyclic AMP had no effect on GTP levels, indicating that the dopamine-stimulated increase of GTP is independent of the catalytic production of cyclic AMP by adenylate cyclase. Since dopamine-stimulated adenylate cyclase activity requires GTP, the dopamine stimulated increase in GTP concentration described in this report may serve to facilitate dopamine stimulation of adenylate cyclase activity. PMID- 2580826 TI - Phosphotyrosyl-specific protein phosphatase activity of a bovine skeletal acid phosphatase isoenzyme. Comparison with the phosphotyrosyl protein phosphatase activity of skeletal alkaline phosphatase. AB - A partially purified bovine cortical bone acid phosphatase, which shared similar characteristics with a class of acid phosphatase known as tartrate-resistant acid phosphatase, was found to dephosphorylate phosphotyrosine and phosphotyrosyl proteins, with little activity toward other phosphoamino acids or phosphoseryl histones. The pH optimum was about 5.5 with p-nitrophenyl phosphate as substrate but was about 6.0 with phosphotyrosine and about 7.0 with phosphotyrosyl histones. The apparent Km values for phosphotyrosyl histones (at pH 7.0) and phosphotyrosine (at pH 5.5) were about 300 nM phosphate group and 0.6 mM, respectively, The p-nitrophenyl phosphatase, phosphotyrosine phosphatase, and phosphotyrosyl protein phosphatase activities appear to be a single protein since these activities could not be separated by Sephacryl S-200, CM-Sepharose, or cellulose phosphate chromatographies, he ratio of these activities remained relatively constant throughout the purification procedure, each of these activities exhibited similar thermal stabilities and similar sensitivities to various effectors, and phosphotyrosine and p-nitrophenyl phosphate appeared to be alternative substrates for the acid phosphatase. Skeletal alkaline phosphatase was also capable of dephosphorylating phosphotyrosyl histones at pH 7.0, but the activity of that enzyme was about 20 times greater at pH 9.0 than at pH 7.0. Furthermore, the affinity of skeletal alkaline phosphatase for phosphotyrosyl proteins was low (estimated to be 0.2-0.4 mM), and its protein phosphatase activity was not specific for phosphotyrosyl proteins, since it also dephosphorylated phosphoseryl histones. In summary, these data suggested that skeletal acid phosphatase, rather than skeletal alkaline phosphatase, may act as phosphotyrosyl protein phosphatase under physiologically relevant conditions. PMID- 2580827 TI - Negative modulation of sodium channels in cultured chick muscle cells by the channel activator batrachotoxin. AB - We have investigated the possibility that cellular control of membrane excitability involves feedback mechanisms in which the degree of activity of voltage-sensitive Na+ channels regulates the number of these channels. Using two independent assays, channel-mediated Na+ uptake and the specific binding of [3H] saxitoxin, we have studied the effects of pharmacological activation of Na+ channels with batrachotoxin (BTX) on the number and properties of these channels. Upon exposure of cultured muscle cells to BTX (1 microM), the number of surface Na+ channels decreases by approximately 75%, with a half-time of 3-6 h. This decrease is prevented by pharmacological blockade of these channels and does not reflect changes in the apparent affinities towards either BTX or saxitoxin. This reduction is reversible: a gradual increase in surface Na+ channels that is dependent on protein synthesis is observed upon removal of the activator. The BTX induced decrease in Na+ channels is associated with an enhanced rate of disappearance of surface Na+ channels. These findings point to the existence of a down-regulation mechanism for the modulation of membrane excitability under conditions of elevated Na+ channel activity. PMID- 2580828 TI - Immunological analysis of alpha 1-microglobulin in different mammalian and chicken serum. alpha 1-Microglobulin is 5-8 kilodaltons larger in primates. AB - Heterologous radioimmunoassays for a semiquantitative analysis of alpha 1 microglobulin were developed, exploiting the binding between polyclonal rabbit or goat antisera against human, guinea pig, or rat alpha 1-microglobulin and 125I labeled human, guinea pig, or rat alpha 1-microglobulin. Homologues of this protein were detected in human, guinea pig, Rhesus monkey, rat, mouse, rabbit, goat, horse, and cow serum by inhibition of a set of heterologous radioimmunoassays. Serum proteins were separated by gel chromatography, and fractions were pooled, concentrated, and radiolabeled with 125I. By immunoprecipitation of the radioiodinated serum pools with heterologous anti alpha 1-microglobulin-sera, and separating the precipitates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, analogues of alpha 1-microglobulin were isolated from serum of man, guinea pig, Rhesus monkey, rat, mouse, horse, and chicken. The apparent molecular weight of alpha 1-microglobulin was 31,000 32,000 in human and monkey serum and 24,000-26,000 in guinea pig, rat, mouse, horse, and chicken serum. The possibility of an addition of a 5,000-8,000-Da peptide in primate alpha 1-microglobulin is discussed. PMID- 2580829 TI - Coordinate induction of alcohol dehydrogenase 1, aldolase, and other anaerobic RNAs in maize. AB - Anaerobiosis results in the selective synthesis of a particular set of polypeptides in the maize root including the two alcohol dehydrogenases (Sachs, M. M., Freeling, M., and Okimoto, R. (1980) Cell 20, 761-768), pyruvate decarboxylase (Wignarajah, K., and Greenway, H. (1976) New Phytol. 77, 575-584; Laszlo, A., and St. Lawrence, P. (1983) Mol. Gen. Genet. 192, 110-117), glucose phosphate isomerase (Kelley, P. M., and Freeling, M. (1984) J. Biol. Chem. 259, 673-677) and aldolase (Kelley, P. M., and Freeling, M. (1984) J. Biol. Chem. 259, 14180-14183). This report describes the identification and characterization of cDNA clones to five different mRNA species induced upon anaerobic shock. Immunoprecipitation of hybrid-selected translation polypeptides has determined the identity of the cDNA clone for fructose-1,6-diphosphate aldolase mRNA. Quantitative hybridization analysis of anaerobic mRNAs using the cDNA clones has shown that there is not a simultaneous accumulation of anaerobic mRNAs. Upon reintroduction of air, the anaerobic mRNAs disappear rapidly and at approximately the same rate. A translocation line that generates progeny that contain 1, 2, and 3 doses of the long arm of chromosome one (1L) allowed us to test for clustering of the anaerobic genes; two of the anaerobic genes tested do not reside with Adh 1 and Phi 1 on the long arm of chromosome 1. PMID- 2580830 TI - The human alpha-fetoprotein gene. Sequence organization and the 5' flanking region. AB - The human alpha-fetoprotein (AFP) gene was isolated into three overlapping clones in bacteriophage lambda vectors and its sequence organization analyzed by restriction endonuclease mapping and nucleotide sequencing. The human AFP gene is about 20 kilobase pairs long and contains 15 exons and 14 introns. The overall organization of the human AFP gene is similar to that of the mouse AFP gene, with all but two exons showing identical sizes. Nucleotide sequences at all exon/intron junctions display similarity to the consensus boundary sequence (Breathnach, R., and Chambon, P. (1981) Annu. Rev. Biochem. 50, 349-383), with the GT-AG rule applied to the splicing point. The cap site maps 44 nucleotides upstream from the translation initiation site. The "TATA box" is located 27 nucleotides upstream from the putative cap site and is flanked by sequences with dyad symmetry. The TATA box can thus be placed in the loop portion of a possible stem-loop structure formed by intrastrand base-pairing. Other characteristic nucleotide sequences in the 5' flanking region include a CCAAC pentamer, a 14 base pair (bp) enhancer-like sequence, and a 9-bp sequence homologous to the glucocorticoid responsive element. A long (90 bp) direct repeat and several alternating purine/pyrimidine sequences are also present in the 5' flanking region. A 736-bp sequence of the 5' flanking region adjacent to the cap site of the human AFP gene shows a 61% similarity with the corresponding region of the mouse AFP gene. There are two Alu family sequences and two poly(dT-dG) repeats in the human AFP gene that show different distribution patterns from those in the mouse AFP gene. PMID- 2580831 TI - Modulation of apolipoprotein B antigenic determinants in human low density lipoprotein subclasses. AB - To investigate the effect of low density lipoprotein (LDL) heterogeneity on the conformation of LDL apolipoprotein B (apo-B), the immunoreactivities of 6 monoclonal antibodies against LDL apo-B were measured in 3 LDL subfractions isolated by equilibrium density gradient ultracentrifugation. To ensure a broad range of LDL particles, the LDL subfractions were prepared from normal subjects and patients with hyperapobetalipoproteinemia. With 3 of the antibodies, 1D1, 5E11, and 3A10, LDL fractions 1 (the most buoyant), 2 (the intermediate), and 3 (the densest) were equally immunoreactive and competed similarly with reference whole LDL. In contrast, with 3 other antibodies, 2D8, 3F5, and 4G3, fraction 1 was significantly more reactive than fraction 3; that is for each in turn, 290, 250, and 150% more of the densest LDL protein was required to achieve the same displacement as with fraction 1. Further, the immunoreactivities of the 3 LDL fractions with antibodies 2D8, 3F5, and 4G3 were negatively correlated with their LDL cholesterol to LDL protein ratio with r values of 0.727, 0.898, and 0.870, respectively, suggesting that as LDL particle size decreases, the conformation of the LDL apo-B changes progressively. It is of interest that the antigenic determinants recognized by 3F5 and 4G3 are close to the LDL receptor recognition site on LDL apo-B. Therefore, it is possible that the reduced immunoreactivity of these determinants in dense LDL may be the in vitro correlate of the reduced fractional catabolics rate of dense LDL compared to buoyant LDL previously observed in vivo. PMID- 2580832 TI - Membrane insertion of alpha- and beta-subunits of Na+,K+-ATPase. AB - Insertion of the alpha- and beta-subunits of amphibian epithelial Na+,K+-ATPase into pancreatic microsomes in cell-free systems was shown to be the same as into membranes of intact cells. The glycoproteic beta-subunit was observed to be cotranslationally inserted into endoplasmic reticulum membranes and to adopt a different pattern of N-linked core and terminal sugars in two different amphibian species. The beta-subunit lacks a cleavable signal sequence but quantitative membrane integration required membrane addition at the start of synthesis. Proteolysis of beta-subunit assembled in vitro indicated a cleavable cytoplasmic domain of about 2000 daltons. The catalytic 98-kilodalton alpha-subunit was also membrane-associated during its synthesis in an alkali-resistant fashion and independent of newly synthesized beta-subunit. In contrast to the beta-subunit, membrane integration of the alpha-subunit was possible as late as a time point in its synthesis which corresponded to about 1/3-1/2 of completion of the nascent chain. A small 34 kDa trypsin-resistant fragment of the alpha-subunit was produced at an early stage of synthesis both in the intact cell and in the cell free system. These results suggest that membrane insertion of both alpha- and beta-subunit occurs during their synthesis but with a different time course. PMID- 2580833 TI - A new approach to the study of the base-excision repair pathway using methoxyamine. AB - This paper describes the use of methoxyamine to study the enzymatic reactions catalyzed by uracil-DNA glycosylase and by AP (apurinic/apyrimidinic) endodeoxyribonuclease isolated from mammalian cells. [14C]Methoxyamine permits one to follow the formation of AP sites in a uracil-containing polydeoxyribonucleotide incubated with calf thymus uracil-DNA glycosylase. The number of methoxyamine-reacted AP sites is equal to that of uracil released. Methoxyamine has no effect on the uracil-DNA glycosylase activity and may be added together with the enzyme in order to block the AP sites and prevent the degradation of the polynucleotide by the AP endonucleases that may be present in a crude preparation. Addition of methoxyamine to AP sites prevents not only the enzymatic hydrolysis of the adjacent phosphodiester bond but also the degradation of the polynucleotide by NaOH. This protective effect disappears after methoxyamine is removed by acetaldehyde. PMID- 2580834 TI - Purification and characterization of guinea pig liver morphine 6-dehydrogenase. AB - Morphine 6-dehydrogenase, which catalyzes the dehydrogenation of morphine to morphinone, has been purified about 440-fold from the soluble fraction of guinea pig liver with a yield of 38%. The purified enzyme was a homogeneous protein on polyacrylamide gel disc electrophoresis and isoelectric focusing. The molecular weight and isoelectric point of the enzyme were 29,000 and 7.6, respectively. The enzyme utilizes both NAD and NADP as a cofactor, and the Km values were 0.12 mM for NAD and 0.42 mM for NADP. The Vmax values for morphine were 588 milliunits/mg of protein (with NAD) and 1600 milliunits/mg of protein (with NADP). The Km values for morphine were 0.12 mM (with NAD) and 0.49 mM (with NADP). The enzyme also exhibited activity for morphine-related compounds: nalorphine, normorphine, codeine, and ethylmorphine; however, 7,8-saturated congeners such as dihydromorphine and dihydrocodeine were poor substrates. The enzyme was inactivated by removal of 2-mercaptoethanol from the enzyme solution. The inactivated enzyme was rapidly recovered by the addition of 2-mercaptoethanol. Phenylarsine oxide and CdCl2 (dithiol modifiers) inhibited competitively toward cofactor binding and noncompetitively toward morphine binding. These results suggest that the enzyme possesses the essential thiol groups, probably vicinal dithiol, at or near the cofactor-binding site. Using the partially purified enzyme, 8-(2-hydroxyethylthio)dihydromorphinone was isolated as the product and identified by UV, mass, and NMR spectra. It was confirmed that morphinone proposed as the dehydrogenation product was nonenzymatically and covalently bound to 2-mercaptoethanol. Accordingly, the isolated morphinone-2-mercaptoethanol conjugate must be formed by two steps: enzymatic production of morphinone from morphine and then nonenzymatic binding of 2-mercaptoethanol to morphinone. PMID- 2580835 TI - Identification of prolipoprotein signal peptidase and genomic organization of the lsp gene in Escherichia coli. AB - The product of the lsp gene of Escherichia coli, i.e. the prolipoprotein signal peptidase, was identified by both in vivo pulse labeling experiments using a high expression lambda PL promoter vector and by an in vitro transcription/translation coupled system. The molecular weight of prolipoprotein signal peptidase was estimated to be approximately 18,000 by its mobility on polyacrylamide gel electrophoresis and was found to be the same as that of SPase II purified from the wild-type cells. Analysis of SPase II activities in strains containing various subclones, deletion derivatives generated from plasmid pMT521, and analysis of protein products in a strain harboring an ileS-lsp-fused gene indicated that ileS and lsp genes are transcribed on the same mRNA. This was further supported by the observation that Tn5 insertions in the ileS gene resulted in a reduced expression of the lsp gene. In addition to an upstream promoter shared by the ileS and lsp genes, these analyses also revealed the presence of an internal promoter for the lsp gene within the coding region of the ileS gene. PMID- 2580836 TI - The irreversible binding of azacytosine-containing DNA fragments to bacterial DNA(cytosine-5)methyltransferases. AB - DNA containing 5-azacytosine is an irreversible inhibitor of DNA(cytosine 5)methyltransferase. This paper describes the binding of DNA methyltransferase to 32P-labeled fragments of DNA containing 5-azacytosine. The complexes were identified by gel electrophoresis. The EcoRII methyltransferase specified by the R15 plasmid was purified from Escherichia coli B(R15). This enzyme methylates the second C in the sequence CCAGG and has a molecular mass of 60,000 Da. Specific binding of enzyme to DNA fragments could be detected if either excess unlabeled DNA or 0.8% sodium dodecyl sulfate was added to the reaction mixture prior to electrophoresis. Binding was dependent upon the presence of both the CCAGG sequence and azacytosine in the DNA fragment. S-Adenosylmethionine stimulated the formation of the complex. The complex was stable to 6 M urea but could be digested with pronase. These DNA fragments could be used to detect the presence of several different methyltransferases in crude extracts of E. coli. No DNA protein complexes could be detected in E. coli B extracts, a strain that contains no DNA(cytosine-5)methyltransferases. The chromosomally determined methylase with the same specificity as the purified EcoRII methylase could be detected in crude extracts of E. coli K12 strains. The MspI methylase cloned in E. coli HB101 could also be detected in crude extracts. These enzymes are the only proteins that bind azacytosine-containing DNA in crude extracts of E. coli. PMID- 2580837 TI - Isolation and characterization of three rat U3 RNA pseudogenes colinear with U3 RNA. AB - Three different 15-kilobase rat genomic clones that contained sequences colinear with U3 RNA were isolated. These inserts hybridized only to U3 RNA in a mixture of total cellular 4-8 S RNA labeled in vivo which showed that genes or pseudogenes for most other small RNAs were absent in these U3 DNA clones. DNA sequence analysis showed that the three subcloned genes contained full-length U3 coding sequences but each had sequence variations, insertions, and/or deletions when compared to rat U3A or U3B RNA. Two of these pseudogenes contained poly(A) sequences on the 3'-end and were flanked by 6-15-nucleotide long direct repeats. None of the three clones was transcribed when injected into Xenopus oocyte nuclei. One clone was a template for a small RNA slightly larger than U3 RNA, but this transcript was not related to the U3 RNA sequences. The structural features of two of these three U3 DNAs are supportive of the hypothesis that some pseudogenes arose from RNA-mediated DNA synthesis and insertion into the genome at random sites (Van Arsdell, S. W., Denison, R.A., Bernstein, L.B., Weiner, A.M., Manser, T., and Gesteland, R.F. (1981) Cell 26, 11-20). This is the first instance where full-length, colinear, U3 RNA pseudogenes have been isolated and characterized. PMID- 2580838 TI - Cleavage of stem-and-loop structure DNA by bleomycin. Reaction on the bacteriophage G4 origin of complementary strand synthesis. AB - The cleavage by bleomycin-Fe(II) complex in the presence of dithiothreitol of 3' or 5'-end-labeled DNA from the region of the bacteriophage G4 origin of complementary strand synthesis was investigated by using the DNA-sequencing technique. Bleomycin cleaved a single-stranded DNA substrate preferentially at inverted repeat sequences, which potentially form stem-and-loop structures, while it cleaved double-stranded DNA substrates with different specificity. The results support the formation of three adjoining stem-and-loop structures in the region of the phage G4 origin of complementary strand synthesis under the low-salt conditions used and suggest a difference in the form of the double helix between the stem and the double-stranded DNA fragment. Bleomycin appears to be a useful reagent for searching stem-and-loop structures. The results may also contribute to the understanding of the mode of action of bleomycin as an antitumor antibiotic. PMID- 2580839 TI - Effect of anion-specific inhibitors on the utilization of sugar nucleotides for N linked carbohydrate unit assembly by thyroid endoplasmic reticulum vesicles. AB - The effect of anion-specific inhibitors on the utilization of the sugar nucleotides (UDP-glucose, GDP-mannose, and UDP-N-acetylglucosamine) required for the formation of the oligosaccharide-lipid involved in N-glycosylation has been studied in intact endoplasmic reticulum (ER) vesicles from thyroid. Of the reagents tested, the nonpenetrating probe DIDS (4,4'-diisothiocyano-2,2' stilbenedisulfonic acid) and its dihydro derivative (H2DIDS) were the most effective, causing a pronounced impairment in the synthesis from UDP-Glc of dolichyl phosphate (Dol-P) glucose (50% reduction at 60 microM DIDS) and in the incorporation of glucose into oligosaccharide-lipid and N-glycosylated protein; in contrast, no inhibition was observed in the formation from UDP-Glc of a glycogen-like proteoglucan. The specificity of the DIDS effect was indicated by the finding that methyl isothiocyanate, a nonanionic amino-reactive agent, demonstrated negligible inhibition. While DIDS also effected a block in the formation of Dol-P-P-GlcNAc from UDP-GlcNAc, no impairment in the utilization of GDP-Man for Dol-P-Man synthesis was observed. Since the DIDS inhibition of UDP Glc and UDP-GlcNAc utilization was maintained after disruption of the ER vesicles with Triton, even when the incubations were supplemented with Dol-P, it appears that this reagent does not interact with sugar nucleotide translocator proteins but rather with the cytoplasmically oriented anion binding sites of glycosyltransferases (UDP-Glc- and UDP-GlcNAc:Dol-P glucosyl- and GlcNAc-1-P transferases). This is consistent with the protease sensitivity of these enzymes in the intact ER vesicles. Incubation of the vesicles with tritiated H2DIDS (8 microM) introduced radioactivity into membrane polypeptides with molecular weights of about 52,000 and 31,000 as observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, suggesting that this inhibitor may prove useful as an affinity label in further studies of some of the glycosyltransferases involved in the synthesis of lipid-monosaccharide intermediates. PMID- 2580840 TI - The beta subunits of glycoprotein hormones. Formation of three-dimensional structure during cell-free biosynthesis of lutropin-beta. AB - The folding of the hormone-specific (beta) subunit of the glycoprotein hormone bovine lutropin was studied after the translation and processing of bovine pituitary mRNA in a system derived from Krebs ascites tumor cells. Of the three forms of beta subunit recognized in this system, only the subunit which had both its prepeptide removed and an oligosaccharide moiety attached formed a tertiary structure which could be immunoprecipitated by an antiserum specific to isolated (folded) lutropin-beta. This glycosylated subunit also combined with added alpha subunit to form the dimeric alpha-beta complex. The results of the translation and processing experiments parallel those of previous experiments in which alpha subunit folding was examined. In contrast to alpha subunit, however, the difficulty of demonstrating correct refolding of beta subunit after reduction and reoxidation of its disulfide bonds strongly suggests that the formation of its correct tertiary structure not only requires carbohydrate attached to the peptide chain but also must occur during formation of the nascent beta chain. PMID- 2580841 TI - The identification of diphtheria, tetanus and pertussis vaccines by single radial and double immunodiffusion techniques. AB - The identification tests for adsorbed diphtheria, tetanus and pertussis vaccines, which are required by the European Pharmacopoeia to be undertaken in animals, may be replaced by precipitation tests, for instance in agaros gels. Such in vitro tests eliminate the use of animals and are less expensive and time-consuming. The single radial immunodiffusion technique is a suitable semiquantitative test, while the double diffusion test is necessary for the investigation of complete or partial identity. The precipitates obtained in the single radial diffusion tests and in double diffusion tests with diphtheria toxoid were visible without staining; those obtained in the double diffusion tests with tetanus toxoid were weaker and staining was sometimes needed. PMID- 2580842 TI - Single radial immunodiffusion as a method for the identification and quantitation of diphtheria and tetanus toxoids in adsorbed vaccines. AB - The immunochemical techniques of double diffusion and single radial diffusion in agarose gels were compared and each considered as possible alternative methods to the methods stipulated by the European Pharmacopoeia for the identification of diphtheria and tetanus toxoids in adsorbed vaccines. Both methods identified the toxoids but single radial diffusion was found to be preferable as the precipitin bands formed were visible without staining. Single radial diffusion was further investigated for its suitability as a quantitative method and was found to give reproducible estimates of the amount of toxoid present in all vaccines tested. However, in the case of tetanus toxoids these estimates were lower than the amounts stated to have been incorporated in the vaccines by the manufacturers. It was concluded that single radial diffusion would be a suitable replacement in the European Pharmacopoeia as a method for the identification of the diphtheria and tetanus components of adsorbed vaccines provided that elution could also be achieved from vaccines containing calcium phosphate. PMID- 2580843 TI - Effect of substance P and other tachykinins on arterial pressure in guinea-pigs. AB - The blood pressure and respiratory effects of i.v. administration of the tachykinins substance P (SP), physalaemin (P), eledoisin (E) and kassinin (K) and purported antagonists of SP were compared in guinea-pigs anaesthetized with sodium pentobarbital. Tachykinins caused a dose-dependent decrease in diastolic and systolic pressure with systolic pressure decreased more than diastolic. Heart rate was not affected. Duration of response was directly related to dosage. These data are in agreement with observations that tachykinins decrease peripheral vascular resistance in other species. Tachyphylaxis did not develop to the vascular actions of tachykinins. Comparison of ED50's demonstrated a rank order of potency of SP greater than P congruent to E greater than K suggesting that the vascular receptor for SP is of the SP-P type. Analysis of the regression lines for log dose of tachykinin vs. percent decrease in diastolic blood pressure revealed similar slopes for SP and E and for P and K. The maximal response caused by P was greater than that caused by SP, E or K. These observations are not consistent with postulated classifications of tachykinins or tachykinin receptors suggesting that undefined tissue factors may have affected the relative in vivo potencies of these peptides. Apnoea occurred with K and E throughout the effective dosage range. SP caused apnoea only in doses in excess of those causing maximal vasodilation. P did not cause apnoea. These observations suggest that the SP-receptor mediating respiratory depression is of the SP-E type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580844 TI - Identification of osteoclast-specific monoclonal antibodies. AB - Studies on the origin, identification, and characterization of osteoclasts have been difficult. This is in part due to a lack of definitive osteoclast markers and the similarity of these cells in form and function to cells of the mononuclear phagocyte system. To solve this problem, we inoculated isolated chick osteoclasts into mice to generate osteoclast-specific monoclonal antibodies. Supernatants from growth-positive hybridomas were screened by indirect immunofluorescent methods against cultured osteoclasts, monocyte-derived multinucleated giant cells, cultured monocytes, fibroblasts, and limb mesenchyme. Select hybridomas were cloned to produce 375 clones, which were analyzed as described above. Antibody from select clones was also reacted with paraffin sections of bone. In addition, two clones have been analyzed by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Antibody binding from an osteoclast-specific clone and a clone reactive with osteoclasts, giant cells, and cultured monocytes (as determined by immunohistochemical assay) was confirmed by antibody-binding and titration curves quantitated by ELISA. The above studies demonstrate that osteoclast specific antigens exist, and that osteoclasts, giant cells, and cultured monocytes share common determinants not found on other cells screened. PMID- 2580845 TI - Gliding movement of and bidirectional transport along single native microtubules from squid axoplasm: evidence for an active role of microtubules in cytoplasmic transport. AB - Native microtubules prepared from extruded and dissociated axoplasm have been observed to transport organelles and vesicles unidirectionally in fresh preparations and more slowly and bidirectionally in older preparations. Both endogenous and exogenous (fluorescent polystyrene) particles in rapid Brownian motion alight on and adhere to microtubules and are transported along them. Particles can switch from one intersecting microtubule to another and move in either direction. Microtubular segments 1 to 30 microns long, produced by gentle homogenization, glide over glass surfaces for hundreds of micrometers in straight lines unless acted upon by obstacles. While gliding they transport particles either in the same (forward) direction and/or in the backward direction. Particle movement and gliding of microtubule segments require ATP and are insensitive to taxol (30 microM). It appears, therefore, that the mechanisms producing the motive force are very closely associated with the native microtubule itself or with its associated proteins. Although these movements appear irreconcilable with several current theories of fast axoplasmic transport, in this article we propose two models that might explain the observed phenomena and, by extension, the process of fast axoplasmic transport itself. The findings presented and the possible mechanisms proposed for fast axoplasmic transport have potential applications across the spectrum of microtubule-based motility processes. PMID- 2580847 TI - Monoclonal antibody to intermediate filament antigen cross-reacts with higher plant cells. AB - The monoclonal antibody (anti-IFA) raised (Pruss et al., 1981, Cell 27:419-428) against an intermediate filament antigen, which is widespread throughout phylogeny, has been shown here to cross-react with higher plants. On immunoblotting, anti-IFA cross-reacted with proteins in homogenates of carrot suspension cells and of meristematic cells from onion root tips. A 50-kD cross reactive protein was enriched in a fraction that consisted of detergent-insoluble bundles of 7-nm fibrils from carrot protoplasts (Powell et al., 1982, J. Cell Sci. 56:319-335). By use of indirect immunofluorescence, anti-IFA stained formaldehyde-fixed onion meristematic cells and carrot protoplasts in patterns approximating those obtained with monoclonal anti-tubulins. That anti-IFA was not recognizing plant tubulins was established by use of immunoblots of two dimensional gels on which the proteins that comprised isolated fibrillar bundles and taxol-purified carrot tubulins had been separated. The two groups of proteins had different positional coordinates: anti-IFA recognized the fibrillar bundle proteins, and anti-tubulins recognized plant microtubule proteins with no cross reaction to the heterologous proteins. Likewise, formaldehyde-fixed taxol microtubules from carrot cells could be stained with anti-tubulin but not with anti-IFA. It is concluded that an epitope common to intermediate filaments from animals co-distributes with microtubules in higher plant cells. PMID- 2580846 TI - Fluorescent morphological probe for hyaluronate. AB - Hyaluronate levels change dramatically during morphogenesis of various tissues and organs. Morphological detection of the exact temporal and spatial distribution patterns of hyaluronate may help to elucidate its role in morphogenesis. Since no specific direct method for visualizing hyaluronate with the light or electron microscope is currently available, we have developed a morphological probe by exploiting the high-affinity interaction of cartilage proteoglycan with hyaluronate. The core protein of this proteoglycan consists of a region that binds specifically to hyaluronate with a high association constant, and a region to which the majority of sulfated polysaccharide chains are covalently attached. The polysaccharide chains were removed by treatment with chondroitinase ABC, and the core protein, labeled with rhodamine, was used as the probe. This fluorescent probe binds reversibly and specifically to [3H]hyaluronate in a binding assay using ammonium sulfate precipitation of the core protein. The probe has been used to visualize the cell surface hyaluronate of rat fibrosarcoma cells, 3T3 cells, and SV-40 transformed 3T3 cells, three cell types with significantly different amounts of cell surface-associated hyaluronate. PMID- 2580848 TI - Transport by the (Na+,K+) ATPase: modulation by differentiation inducers and inhibition of protein synthesis in the MDCK kidney epithelial cell line. AB - MDCK kidney epithelial cell cultures exposed to the differentiation inducer hexamethylene bisacetamide (HMBA) for 24 hours exhibited a 50% decrease in transport activity per (Na+,K+)-ATPase molecule (turnover number) but an unchanged number of pump sites (Kennedy and Lever, 1984). Inhibition of protein synthesis by either 10 microM cycloheximide or 2 microM emetine blocked the inhibitory effects of HMBA on Na+/K+ pump efficiency assessed by measurements of [3H]-ouabain binding to intact cells, (Na+,K+) ATPase activity of detergent activated cell extracts, and ouabain-sensitive Rb+ uptake. In the absence of inducer treatment, inhibition of protein synthesis increased Na+/K+ pump turnover number by twofold while maintaining Na+/K+ pump activity per cell at a constant level. Intracellular Na+ levels were decreased after cycloheximide treatment; therefore, pump stimulation was not due to substrate effects. Furthermore, cycloheximide effects of Rb+ uptake could be dissociated from effects on tight junctions. These observations suggest that the transport activity of the (Na+,K+) ATPase is tightly regulated by factors dependent on protein synthesis. PMID- 2580849 TI - Variable expression of Qa-m7, Qa-m8, and Qa-m9 antigenic determinants on primitive hemopoietic precursor cells. AB - Using monoclonal antibodies, we have analysed the distribution of three recently described Qa antigenic determinants (Qa-m7, Qa-m8 and Qa-m9) on murine clonable hemopoietic progenitor cells and spleen colony-forming units (CFU-S). Cytotoxicity experiments showed that Qa-m7 was expressed on almost all the progenitor cells (colony-forming cells, CFC) of megakaryocytes (MEG-CFC), erythroid cells (E-CFC), B lymphocytes (BL-CFC), and mixed colonies (MIX-CFC) as well as day 13 CFU-S, and a major proportion of granulocyte-macrophage colony forming cells (GM-CFC) and day 8 CFU-S. Experiments using four sources of granulocyte-macrophage colony-stimulating activity suggested differential expression of Qa-m7 on subpopulations of GM-CFC, those preferentially forming macrophage colonies having lowest Qa-m7 antigen density. Immune rosetting techniques demonstrated the selective expression of Qa-m8 on approximately 50% of MEG-CFC, MIX-CFC and day 13 CFU-S, a pattern similar to that of Qa-m2. In contrast, Qa-m9 was not detected on any of the primitive hemopoietic precursors assayed. The results demonstrate the complexity of the Qa antigenic system, and suggest a possible role for these antigens in hemopoietic differentiation. PMID- 2580850 TI - Stimulation of pp60c-src tyrosyl kinase activity in polyoma virus-infected mouse cells is closely associated with polyoma middle tumor antigen synthesis. AB - We have examined the effect of polyoma virus infection of primary mouse embryo cells on the tyrosyl kinase activity associated with the cellular src gene product, pp60c-src. The results of our studies demonstrate that infection of mouse cells with wild-type polyoma virus or viral mutants capable of transforming rodent cells in culture and inducing tumors in animals results in the stimulation of pp60c-src tyrosyl kinase activity. The level of pp60c-src kinase stimulation in infected cells was found to be proportional to both the oncogenic potential of the virus strain used for infection and the characteristic phenotype of rodent cells transformed by the various strains of polyoma virus. Stimulation of pp60c src kinase activity was not observed in mouse cells infected with transformation defective strains of polyoma virus. In examining the kinetics of pp60c-src kinase stimulation in mouse cells at various times following wild-type polyoma virus infection, we found that the level of pp60c-src kinase activity correlated directly with the synthesis of polyoma virus-encoded tumor antigens. By comparing wild-type polyoma virus with other viral mutants in these experiments, we conclude that the stimulation of pp60c-src kinase activity in mouse cells following polyoma virus infection is associated with the synthesis of middle tumor antigen. PMID- 2580851 TI - Domain structure of neurofilament subunits as revealed by monoclonal antibodies. AB - Monoclonal antibodies have been prepared against purified neurofilament (NF) subunits (NF68, NF150, and NF200). From 25 fusions, several hundred strongly positive antibodies have been obtained. Among them are antibodies against the specific subunits as well as antibodies recognizing common antigenic determinants. These have all been characterized according to the following properties: ELISA (enzyme-linked immunosorbant assay) testing against each subunit, immunoblots against enriched neurofilament preparation, immunoblots of cyanogen bromide or chymotrypsin-treated neurofilaments, immunofluorescence with PC12 cells, and immunohistochemistry of cerebellum. Whereas the antibodies against the NF68 and NF150 appear to react with single cyanogen bromide fragments, the antibodies against the NF200 react with multiple cyanogen bromide fragments. These data are consistent with the hypothesis that the NF200 is partially composed of several repeated structural determinants. Furthermore, all of the antibodies that react with the NF200 recognize the solubilized "sidearm" domain from limited chymotryptic digestions. The locations of the common and variable domains of the three subunits are discussed in light of these results. PMID- 2580852 TI - Activators of protein kinase C and 5-azacytidine induce IL-2 receptor expression on human T lymphocytes. AB - Resting human T lymphocytes do not express receptors for interleukin-2, but expression is rapidly induced by exposure to PHA. After maximal expression 2-3 days after stimulation, a progressive decline in receptor number is observed. Receptor expression can be augmented by reexposure to PHA. In this study we show that activators of protein kinase C including phorbol diester, phospholipase C, and the diacylglycerol congener diC8 also increase IL-2 receptor expression. Moreover, 5-azacytidine, which inhibits cytosine methyltransferase, and hydroxyurea, which inhibits ribonucleotide reductase, also increased receptor number. These studies demonstrate that IL-2 receptor expression can be altered in vitro, and that IL-2 receptor number, in combination with IL-2 secretion, may contribute to the regulation of IL-2-dependent immune responses. PMID- 2580853 TI - Polyamine biosynthesis in the developing rabbit palate. AB - Levels of putrescine, spermidine, and spermine and their biosynthetic enzymes, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) were measured in the developing rabbit palate between day 14 and day 18 of gestation. DNA, RNA, and protein synthesis were also measured during this time period to determine if a correlation exists between polyamine biogenesis and macromolecular synthesis. ODC activity was found to be twice as high on day 14 as on the succeeding days of gestation, while SAMDC activity did not change significantly. Levels of putrescine and spermine were higher on day 14 by 22% and 30%, respectively, than levels on day 18. Spermidine concentration did not change. DNA synthesis remained relatively constant between days 14 and 18 of gestation, suggesting that there is no peak in cell proliferation during this period. RNA synthesis was elevated significantly on day 14 and protein synthesis was significantly higher on both days 14 and 16. This data indicates that there is no correlation between polyamine synthesis and cell proliferation during this period of palatal development, but polyamines could play a regulatory role in RNA and/or protein synthesis. PMID- 2580854 TI - An ultrastructural and histochemical study of the development of secondary palate in Japanese quail, Coturnix coturnix japonica. AB - Embryonic development of the secondary palate of the Japanese quail, Coturnix coturnix japonica, was studied. The palatal shelves appeared on day 5 of incubation in a horizontal direction over the dorsal surface of the tongue. Subsequently, unlike those in mammals, the opposing palatal shelves do not fuse, and a physiological cleft persists between them. In comparison with the chick, where the palatal shelves do not fuse and the medial edge epithelium (MEE) becomes orthokeratinized stratified squamous type, the quail MEE differentiates into a parakeratinized stratified squamous type. The basal cells of the quail MEE differentiated from cuboidal to columnar and showed reorganization of their cytoplasmic organelles. In contrast to both the chick and mammalian MEE, quail MEE showed very little ruthenium red (RR) binding at the plasma membrane of both the basal and superficial cells. Initial development in a horizontal direction, lack of fusion, and an absence of programmed cell death in MEE of developing quail palate distinguished it from the mammalian palatogenesis. Also, although the morphogenesis of palate in quail and chick was similar, the pattern of cytodifferentiation in their MEE was different, which may be attributed to their ontogenesis. PMID- 2580855 TI - The common developmental origin and phylogenetic aspects of teeth, rugae palatinae, and fornix vestibuli oris in the mouse. AB - Positional and temporal information is of fundamental importance in understanding the morphogenesis of dentition. In order to determine the fate of epithelial cells localized within specific epithelial thickened regions of the forming mouse maxilla, we analyzed serial histological sections in the frontal plane mouse embryos of 12-15 days' gestation. The epithelial thickening of the oral surface of the maxilla from 12-day embryos was spatially delineated and termed the odontogenic epithelial zone (OEZ). Beginning with 12-day embryos, analyses of camera lucida drawings indicated that the OEZ dissociates into anterior (diastema region) and posterior (molariform tooth organ region) epithelial aggregates that form plate-like configurations. The epithelial plates subsequently divide in a mediolateral direction into the epithelial anlagen of rugae palatinae, teeth, and fornix vestibuli oris superior. The medial and lateral parts of the m1 epithelial anlage are situated in dorsal continuation of both the dental and vestibular laminae of the diastema region. The anlage appears to be of dual origin. The fornix vestibuli oris superior develops from two parts: in the rima oris region from the lip-furrow lined with the vestibular lamina, and in the cheek region from the cheek-furrow in place of fusion of the maxillary and mandibular outgrowths. In 15-day embryos with well-formed secondary palates, the rugae occur, numbering nine on each palatal process. The m1 enamel organ cup excavation is positioned between the level of the fifth extending to the seventh rugae. It appears that the division of the maxillary outgrowth oral epithelial covering into rugae as well as into the dentition anlage is closely related. It is suggested that rugae, the vestibulum oris, and the dentition are developmentally and functionally related, and appear to have a common precursor in both ontogenesis and phylogenesis. PMID- 2580856 TI - Bacteriuria screening by use of acridine orange-stained smears. AB - Acridine orange (AO)-stained smears of 1,042 urine specimens were examined for the presence of bacteria and compared with quantitative culture results. The detection of one or more organisms per three AO fields at X200 magnification was noted in 161 of 162 and 193 of 195 urine specimens that grew greater than 10(5) and 10(4) CFU/ml, respectively, of a clinically relevant organism. However, a high number of false-positive AO smears (356 and 324, respectively) was observed among urines that failed to grow organisms at 10(5) and 10(4) CFU/ml. Sensitivity, specificity, and positive and negative predictive values of AO smears were 99, 58, 26, and 99%, respectively, for cultures of greater than or equal to 10(5) CFU/ml and 98, 59, 32, and 99%, respectively for cultures of greater than or equal to 10(4) CFU/ml. Despite the poor specificity of the AO smear, the very high negative predictive value would allow for the ruling out of bacteriuria defined at 10(4) CFU/ml and would eliminate the need for culture of ca. 50% of the urine specimens in this study. Employment of the rapid, inexpensive AO procedure only as a means to eliminate specimens for culture would allow significant cost savings and permit the laboratory to send out a large number of potentially negative or low-count urine results within a short time of specimen receipt. PMID- 2580857 TI - Cholecystokinin bioactivity in human plasma. Molecular forms, responses to feeding, and relationship to gallbladder contraction. AB - A sensitive and specific bioassay for the measurement of cholecystokinin (CCK) in human plasma was developed to determine the molecular forms of CCK in circulation, CCK responses to feeding, and the physiologic role of CCK in gallbladder contraction. First, plasma was quantitatively extracted and concentrated with octadecylsilylsilica, and the extracts were then assayed for their ability to stimulate amylase release from isolated rat pancreatic acini. Acini were highly sensitive to CCK whereas gastrin reacted only weakly in this system. With the assay, plasma levels of cholecystokinin octapeptide (CCK-8) bioactivity as low as 0.2 pM were detectable. CCK bioactivity in plasma was inhibited by the CCK antagonist, bibutyryl cyclic guanosine monophosphate, and was eliminated by immunoadsorption with an antibody directed against the carboxyl terminus of CCK. Detection of fasting levels of CCK was possible in all individuals tested and averaged 1.0 +/- 0.2 pM (mean +/- SE, n = 22) CCK-8 equivalents. Plasma CCK biological activity was normal in patients with gastrin secreting tumors. After being fed a mixed liquid meal, CCK levels rose within 15 min to 6.0 +/- 1.6 pM. The individual food components fat, protein, and amino acids were all potent stimulants of CCK secretion; in contrast, glucose caused a significant but smaller elevation in plasma CCK levels. Gel filtration studies identified three major forms of CCK bioactivity in human plasma: an abundant form that eluted with CCK-33, a smaller form that eluted with CCK-8, and an intermediate form that eluted between CCK-33 and CCK-8. Ultrasonic measurements of gallbladder volume indicated that this organ decreased 51% in size 30 min after feeding a mixed liquid meal. This contraction occurred coincidentally with the increase in plasma CCK levels. Next CCK-8 was infused to obtain CCK levels similar to postprandial levels. This infusion caused a decrease in gallbladder volume, similar to that seen with a meal. The present studies indicate, therefore, that CCK can be bioassayed in fasting and postprandial human plasma. These studies also suggest that CCK may be an important regulator of gallbladder contraction. PMID- 2580858 TI - Affinity-labeled plasma somatomedin-C/insulinlike growth factor I binding proteins. Evidence of growth hormone dependence and subunit structure. AB - By using disuccinimidyl suberate, we have covalently cross-linked 125I-labeled somatomedin-C (Sm-C)/insulinlike growth factor I to specific binding proteins in human plasma. In unfractionated plasma samples from normal and acromegalic donors, 125I-Sm-C binding-protein complexes with relative molecular weights (Mr) of 160,000, 135,000, 110,000, 80,000, 50,000, 43,000-35,000, and 28,000-24,000 were consistently observed. In contrast, the 43,000-35,000-mol wt species were frequently the only specific complexes observed in hypopituitary plasma and were consistently more intensely labeled in such samples. Reduction of samples with beta-mercaptoethanol did not alter the electrophoretic pattern of these 125I-Sm-C binding-protein complexes. All Sm-C binding proteins, with the exception of the 43,000-35,000-mol wt complex, were adsorbed by concanavalin A-Sepharose. When acromegalic or normal plasma was fractionated on a Sephadex G-200 column and affinity labeled, the same complexes that were adsorbed by concanavalin A were found in fractions that eluted near the gamma-globulin peak. On the other hand, the 43,000-35,000-mol wt complex consistently eluted in size-appropriate fractions near the albumin peak. These data suggest that the growth hormone (GH) dependent Sm-C binding protein, represented by the 160,000-mol wt complex, is in some way composed of smaller species, i.e., the 135,000-, 110,000-, 80,000-, 50,000-, and 28,000-24,000-mol wt complexes. Acid incubation of plasma prior to Sephadex G-200 chromatography results in the elimination of specific 125I-Sm-C binding-protein complexes which elute near gamma-globulin and a concurrent increase in the labeling intensity of the 28,000-24,000-mol wt complexes. We speculate, therefore, that each of the GH-dependent Sm-C binding-protein complexes represents an oligomer composed of 28,000-24,000-mol wt protomers. The 43,000-35,000-mol wt species is not dependent upon GH and appears to represent a different type of Sm-C binding protein. PMID- 2580859 TI - Determination of the hemoglobin F program in human progenitor-derived erythroid cells. AB - The absolute adult and fetal hemoglobin (HbF) contents of the erythroid cells derived from the differentiation of normal human and simian erythroid progenitors and of the peripheral blood erythroid burst-forming units (BFU-E) of patients with nondeletion hemoglobinopathies have been measured with a sensitive radioligand immunoassay. The HbF content varied between 0.13 and 2.96 pg/cell, representing between 0.7% and 19.6% of the total hemoglobin with a mean value of 7.0%. The absolute content of HbF was indistinguishable in the well hemoglobinized progeny of marrow erythroid colony-forming units, marrow or blood BFU-E, or of mixed colony-forming units. The term HbF program refers to this inherent capacity to produce fetal hemoglobin (HbF) in the erythroid cells derived from these progenitors in vitro. The HbF content of marrow erythroblasts as determined by the same radioligand immunoassay was similar to that found in the peripheral blood, suggesting that the switch off of gamma-chain production occurs after the erythroid colony-forming unit stage of maturation. Increasing concentrations of a crude erythropoietin-containing preparation induced higher numbers of erythroid colonies, which were larger in size, but the HbF program was unaffected. In contrast to the hemoglobin accumulation in human progenitor derived colonies, simian progenitor-derived colonies produced considerably more HbF, and the amount of HbF was strongly influenced by progenitor maturity. Assays of the HbF content of erythroblasts derived from culture of the peripheral blood BFU-E of patients with nondeletion hemoglobinopathies and their parents showed that the HbF program in the progenitors of such patients is highly variable. Some produce only a slight excess of HbF in progenitor-derived erythroblasts, whereas others have extraordinarily high HbF programs. The molecular basis of this variability is presently unknown. PMID- 2580860 TI - In vivo interaction of antibodies with cell surface antigens. A mechanism responsible for in situ formation of immune deposits in the zona pellucida of rabbit oocytes. AB - It was the aim of this study to test the hypothesis that the interaction of antibodies with antigens expressed on the plasma membrane of cells surrounded by a basement membrane or a basement membrane-like structure results in in situ formation of immune deposits. Ovary was chosen for the experiments because we found that a well-characterized protein, angiotensin-converting enzyme (ACE), is expressed in a diffuse pattern on the plasma membrane of mature oocytes. To investigate the events following the in vivo interaction of oolemma-ACE with its antibody, rabbits were injected with goat anti-rabbit ACE gamma-globulin or with Fab fragments of goat anti-rabbit ACE IgG in an ear vein for a maximum of 4 d; they were followed for up to 20 d thereafter. Ovary tissue was studied by immunofluorescence, and immunoelectron, light, and transmission electron microscopy. The results of this study document two new findings: First, that ACE is expressed on the oolemma of rabbit oocytes. Second, that the in vivo interaction of divalent antibodies to this cell surface antigen induces formation of granular immune deposits in the adjacent zona pellucida through a mechanism of "patching" and "shedding" of immune complexes, similar to that occurring in in vitro systems characterized by interaction of plasma membrane receptors with soluble ligands. This mechanism might have importance in the pathogenesis of Heymann glomerulonephritis and of other immunological diseases involving antigens expressed on the plasma membrane of cells. PMID- 2580861 TI - Abnormal behavior and low developmental test scores in iron-deficient anemic infants. AB - The relationship between abnormal behavior and poor developmental test performance was analyzed in 68 6- to 24-month-old Guatemalan babies with and without mild iron deficiency anemia. Regardless of age, the 10 anemic infants with abnormal affective responses during developmental testing had very low mental scores (mean = 65.7 +/- 5.2 SEM), while the 18 with normal affect had mental scores (mean = 97.1 +/- 4.5 SEM) which were normal by U.S. standards and comparable to the nonanemic group's scores. Five anemic infants with pervasive behavioral disturbance, who showed abnormal orientation to tasks in addition to disturbed affect, did poorly on the motor test (mean = 59.8 +/- 6.2 SEM). Those anemic infants who were normal in task orientation achieved motor scores similar to those of the nonanemic control group. The observed behavioral disturbances are consistent with biochemical evidence concerning the role of iron in the metabolism of central nervous system neurotransmitters which influence affect and arousal. These results suggest that poor mental developmental test performance in infants with iron deficiency anemia may be mediated by disturbances in affective behavior. PMID- 2580862 TI - Immunocytochemistry in the diagnosis of Whipple's disease. AB - In six cases of Whipple's disease the characteristic macrophages could be stained immunocytochemically using a first layer antiserum to group B streptococci. Other types of periodic acid Schiff positive macrophages were negative. The staining appears to be due to a rhamnose containing polysaccharide as shown by a blocking test. The method may be useful for confirming the diagnosis in rectal biopsy and peripheral nodes, especially if small intestinal findings are atypical. PMID- 2580863 TI - Investigation into the value of Papanicolaou stained cervical smears for the diagnosis of chlamydial cervical infection. AB - Forty five (37%) of 121 female contacts of men with non-gonococcal urethritis or gonorrhoea were chlamydia positive, as judged by isolation or by detecting elementary bodies in smears with a fluorescein labelled chlamydial monoclonal antibody. Only six (13%) of these, however, had Papanicolaou stained smears in which there were inclusion like changes suggestive of chlamydial infection. Furthermore, of 15 patients who had such cytological changes, chlamydiae were detected in only six and the abnormalities were found also in Papanicolaou stained smears from 10 (13%) of the 76 chlamydia negative patients. Modifying the Papanicolaou stained smears by including endocervical material did not increase sensitivity. In addition, destaining and restaining them with the monoclonal antibody was time consuming and the results were unreliable. The staining of cervical smears with Papanicolaou reagent is a technique of low sensitivity and specificity for diagnosing or screening for chlamydial cervical infection and cannot be recommended. PMID- 2580865 TI - Rapid falls in maternal serum alpha-fetoprotein concentrations. AB - The pronounced falls in AFP concentration sometimes seen in samples taken for screening in early pregnancy are consistent with the range of AFP half lives measured in 14 postpartum women of 59-133 h. PMID- 2580864 TI - Effect of neuraminidase on the expression of the 3-fucosyl-N-acetyllactosamine antigen in human tissues. AB - The monoclonal antibody AGF4.48 detects the 3-fucosyl-N-acetyllactosamine carbohydrate structure and reacts with a variety of human tissues, as shown by an immunoperoxidase method on paraffin sections of formalin fixed material. The intensity and distribution of the immunoperoxidase reactivity were affected by treatment of sections with neuraminidase. In some sites, such as bone marrow, brain, breast, and pituitary, the reaction was more intense after neuraminidase treatment. In several organs, including kidney, oesophagus, pancreas, submandibular gland, and uterus, the reaction was more widespread after neuraminidase treatment. Other organs, such as liver, lung, lymph node, skin, and uterine tube, showed an altered distribution of reactivity with AGF4.48 after sections were treated with neuraminidase. These results show that the 3-fucosyl-N acetyllactosamine antigen is cryptic in many tissues. The antigen is masked to a variable extent in different tissues by neuraminic acid residues and can be revealed by the simple procedure of pretreating sections with neuraminidase. The value of using AGF4.48 antibody in combination with the enzyme neuraminidase to show accessible and cryptic antigen is that this reveals distinctive patterns of sialylation within various normal tissues. Whether similar patterns occur in disease will be of particular interest. PMID- 2580867 TI - A symptom approach to the intervention of childhood language disorders. AB - This paper presents a symptom approach for the intervention of childhood language disorders. Intervention guidelines are presented in the following areas of functioning: two word utterances, auxiliaries, grammatical structures, auditory comprehension, discourse, and symbolic play. Behavioral analysis, rather than etiologic classification, forms the basis of the intervention strategies. PMID- 2580866 TI - Comparison of acebutolol and propranolol therapy for ventricular arrhythmias. AB - The effects of acebutolol, a new investigational cardioselective beta blocker, and propranolol on ventricular arrhythmias were compared in 14 patients with more than 30 premature ventricular contractions (PVCs) per hour. Each patient served as their own control, receiving both drugs and placebo in random sequence and in double-blind fashion, with an intervening one-week, drug-free period. Each drug was given for a two-month period, the maximum acebutolol dosage reaching 600 mg tid and the maximum propranolol dosage 80 mg tid. Seventy-two-hour ambulatory electrocardiographic monitoring assessed arrhythmia frequency for each study period. Mean PVC counts did not significantly differ during the two control periods. Acebutolol decreased mean PVC count by 65% (P less than .02), with eight patients exhibiting a 70% or greater decrease. Only three patients exhibited a similar decline with propranolol. The incidence of PVCs was not significantly decreased by propranolol. Acebutolol reduced the number of couplets by 70% (P less than .04), whereas propranolol did not significantly affect couplets. At the dosage of 600 mg tid, acebutolol was well tolerated, effectively suppressed total PVCs and couplets, and appeared to be more effective than propranolol administered at 80 mg tid. PMID- 2580868 TI - Anterograde axonal transport and intercellular transfer of WGA-HRP in trigeminal innervated sensory receptors of rat incisive papilla. AB - The ultrastructure and identification of WGA-HRP-labeled sensory receptors in the rat incisive papilla (the most anterior part of hard palate) were studied using semiserial thin sections. Various sensory receptors were organized according to three locations: dome region (ventral), chemosensory corpuscle region (medial to orifice of incisive canal), and lateral labium (apposing the incisive canal). In the dome region, the sensory receptors were localized in three sensory zones that were associated with surface ridges (one medial and two lateral). In each of these zones, intraepithelial receptor axons and Merkel receptors occurred in the epithelium, while simple unencapsulated corpuscles, glomerular-Meissner corpuscles, and incisive (encapsulated) corpuscles occurred in the lamina propria. In the chemosensory corpuscle region, chemosensory corpuscles and intraepithelial receptor axons were located in the epithelium, and incisive corpuscles were present in the lamina propria. In the lateral labium, only intraepithelial receptor axons were prominent. In all these sensory receptors, the preterminal axons and axon terminals were labeled with the tracer protein. In addition, some nonneuronal cells closely associated with the axon terminals were selectively labeled, e.g., terminal Schwann cells, lamellar Schwann cells, Merkel cells, corpuscular basal cells and chemosensory cells. Other adjacent cells were not labeled, e.g., unspecialized epithelial cells, capsular cells, corpuscular sustentacular cells, and fibroblasts. In both labeled axons and cells, WGA-HRP was incorporated into vesicles, tubules, and vacuolar organelles. The specific intercellular transfer of tracer protein may indicate trophic interactions between axon terminals and support cells in sensory receptors. The specific organization of multiple sensory receptors in the rat incisive papilla may provide a useful alternative system for studying somatosensory physiology. PMID- 2580869 TI - Ataxia-telangiectasia or Louis-Bar syndrome. AB - Ataxia-telangiectasia (A-T) is a clinical syndrome that commonly shows oculocutaneous telangiectasia, progressive cerebellar ataxia, recurrent sinopulmonary infections, increased incidence of malignancy, x-ray hypersensitivity, and autosomal recessive inheritance. Profound dysfunction of both humoral and cell-mediated immune systems is demonstrated by low IgA levels, an immature thymus, a poor response to antigenic challenges, and recurrent infections. The high risk of malignancy may be related to poor immune surveillance. Two cases (sisters) are reported demonstrating the typical features of the disease along with the results of a trial of the immunopotentiating drug, levamisole, in one of them. The features of A-T are reviewed and include the more recent findings of elevated serum carcinofetal proteins and chromosomal aberrations. PMID- 2580870 TI - Relationship between milk production and mammary gland indices of guinea pigs. AB - Regression analysis related simulated production to simulated wet weight of mammary gland, weight of dry fat-free tissue, deoxyribonucleic acid content, and ribonucleic acid content for the first 21 days of lactation of the guinea pig. Coefficients of determination were .52 for wet weight, .03 for dry fat-free tissue, .84 for deoxyribonucleic acid, and .20 for ribonucleic acid. Coefficients of determination were larger when ascending and descending phases of lactation were considered separately. Milk production per unit mammary wet weight, dry fat free tissue, deoxyribonucleic acid, and ribonucleic acid were related to day of lactation by an equation of the form Y = aXbecX, where Y was milk production per unit mammary gland growth, X was day of lactation, e was the base of natural logarithms, and a, b, and c were constants. Efficiency of milk production, defined as milk production per unit mammary size, increased with increasing milk yield. PMID- 2580871 TI - Prevalence and ultrastructural characteristics of bovine mammary corpora amylacea during the lactation cycle. AB - Morphologic and histochemical study of spherical, lamellated inclusion bodies in bovine mammary parenchyma established presence of corpora amylacea. The majority (90%) were in alveolar lumina, followed by stroma (7%) and epithelium (3%). Occurrence of corpora amylacea was unrelated to lactation age, intramammary infection status, milk somatic cell concentration, or milk production. Quantitative analysis demonstrated a progressive increase of prevalence of these structures from the early to later stages of lactation, followed by a return during the late dry period to concentrations at early lactation. Ultrastructural study revealed deeply basophilic, dense, lamellated deposits (70%) and less dense, fibrillar deposits (30%). Dense bodies stained partially or not at all for amyloid but stained for presence of calcium salts, whereas fibrillar bodies were amyloid positive and calcium negative. Corpora amylacea were most prevalent in fully differentiated parenchymal areas (47.1 bodies/unit tissue area of 2.4 X 10(6) micron 2), less numerous in intermediately differentiated areas (23.4), and sparse in nonsecretory areas (7.1). Morphologic relationships between deposits and parenchyma suggest that corpora amylacea suppress milk secretion and flow during late lactation in isolated areas by engorging luminal spaces and clogging small ducts, leading to milk stasis and involution. PMID- 2580872 TI - The odontoblast process: form and function. PMID- 2580873 TI - The role of local factors in dentin and pulp in intradental pain mechanisms. PMID- 2580874 TI - Cellular mechanism of action of cardiac glycosides. AB - It has long been known that cardiac glycosides can inhibit the membrane sodium potassium (Na+-K+) pump, raising intracellular Na+. However, at clinical concentrations of cardiac glycosides, a change in intracellular Na+ that correlates with a change in cardiac contraction has been very difficult to demonstrate. The recent use of Na+-sensitive microelectrodes in the experimental laboratory has made intracellular Na+ measurements possible. A doubling of contraction strength in vitro is associated with a change of only approximately 1 mM intracellular Na+. Another membrane transport system, the Na+-Ca2+ exchange system, exchanges extracellular Na+ for intracellular Ca2+. If this system is responsible for regulating intracellular Ca2+, then it would be very sensitive to the transmembrane Na+ concentration gradient. This influence of intracellular Na+ on Na+-Ca2+ exchange is though to be the cellular basis of the positive inotropic action of digitalis. However, a number of issues remain unresolved, such as the extent of Na+-K+ pump inhibition by the level of cardiac glycoside achieved clinically. PMID- 2580875 TI - Effects of digitalis on cell biochemistry: sodium pump inhibition. AB - It is now generally agreed that Na+-K+ adenosine triphosphatase (ATPase), a transport enzyme derived from the sarcolemmal sodium pump, is the primary site at which digitalis exerts its effects on the myocardial cell. Inhibition of the ability of this ion transport enzyme to catalyze Na+ efflux from the cell in exchange for K+ leads to both the therapeutic and toxic effects of the cardiac glycosides. The mechanism by which digitalis inhibits the sodium pump has been established in studies of Na+-K+ ATPase which show that the ability of cardiac glycosides to inhibit adenosine triphosphate (ATP)-supported transport of Na+ is reduced in the presence of elevated levels of K+. These studies explain the ability of hypokalemia to potentiate the effects of cardiac glycosides on the heart, and of high K+ concentrations to overcome the inhibition of sodium pump activity by the cardiac glycosides. Recent demonstrations that the positive inotropic effect of the cardiac glycosides is correlated with an increased intracellular Na+ provide strong evidence that these effects of digitalis to impair sodium efflux are responsible for the increased myocardial contractility caused by digitalis. PMID- 2580876 TI - Genetic trace metal disturbances. AB - Genetic trace metal disturbances can be at three levels. Trace metals play an important role in the metabolism of genetic macromolecules and the information transfer system. Deficiency or excess of trace metals caused either by dietary or genetic factors will affect the normal functioning of the whole organism. The roles of trace metals in carcinogenesis/mutagenesis and ageing are typical of this category. The second level of genetic trace metal disturbances affect the metabolic pathway of the trace metal itself. Biochemical derangement resulting from genetic defects cause aberrant metabolism of the element and thus disease symptoms. Diseases caused by abnormal metabolism of copper, zinc, iron, and molybdenum are discussed. Trace metal disturbances can also be the result of other genetic diseases. This aspect of genetic trace metal disturbances is least investigated. However, information should be important for improving the existing treatment protocol for the more common inborn errors of metabolism, such as phenylketonuria. PMID- 2580878 TI - Allergens in Hymenoptera venom XV: The immunologic basis of vespid venom cross reactivity. AB - RAST-inhibition studies were performed by use of whole venom sac extracts to inhibit binding to purified venom allergens from various vespid wasps. Immunodiffusion studies were also performed with rabbit antisera raised against purified venom proteins. Immunologic cross-reactivity was demonstrated among the hyaluronidases, phospholipases, and antigen 5 s from both subgenera of yellow jackets, white-faced hornets, and paper wasps. The paper wasp hyaluronidase and antigen 5 were less related to those of the other three species than those of yellow jackets and hornets. It appears that immunologic cross-reactivity is the major mechanism of multiple allergic sensitivity to vespid venoms. Therapy with only the primary venom should be sufficient to protect against reactions from cross-reacting venoms. PMID- 2580877 TI - Clinical and biochemical manifestations of zinc deficiency in human subjects. AB - During the past two decades, essentiality of zinc for man has been established. Deficiency of zinc in man attributable to nutritional factors and several diseased states has been recognized. High phytate content of cereal proteins decreases availability of zinc; thus the prevalence of zinc deficiency is likely to be high in the population subsisting mainly on cereal proteins. Zinc deficiency has been noted to occur in patients with malabsorption syndrome, chronic renal disease, cirrhosis of the liver, sickle cell disease, AE (acrodermatitis enteropathica), and other chronically debilitating diseases. Growth retardation, male hypogonadism, skin changes, poor appetite, mental lethargy, and delayed wound healing are some of the manifestations of chronically zinc-deficient human subjects. In severely zinc-deficient patients, dermatological manifestations, diarrhea, alopecia, mental disturbances, and intercurrent infections predominate. If untreated, the condition becomes fatal. Zinc deficiency affects testicular functions adversely in man and animals. This effect of zinc is at the end-organ level. It appears that zinc is essential for spermatogenesis. Zinc is involved in many biochemical functions. Several zinc metalloenzymes have been recognized in the past decade. Zinc is required for each step of cell cycle in microorganisms and is essential for DNA synthesis. The effect of zinc on protein synthesis may be attributable to its vital role in nucleic acid metabolism. The activities of many zinc-dependent enzymes have been shown to be affected adversely in zinc-deficient tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580879 TI - Silver staining of the nucleolar organizer regions (NORs) on Lowicryl and cryo ultrathin sections. AB - Nucleolar organizer region (NOR) silver staining was applied to sections of fixed material. A positive reaction on cryo-ultrathin sections was found as well as on semithin and ultrathin Lowicryl sections. Repeatable staining that was easy to control was obtained by a one-step procedure after aldehyde-Carnoy fixation. Fixation of the material by formaldehyde and glutaraldehyde alone in cacodylate buffer also maintained reaction selectivity when ammonium chloride was used after fixation. Enzymatic digestion by pronase, RNase A, DNase I, or micrococcal nuclease was applied to ultrathin Lowicryl sections. Pronase digestion removed the silver-stained proteins, whereas digestion by the nucleases did not. A routine procedure is proposed for easy NOR silver staining of sections that preserves a good tissue ultrastructure and is also compatible with cytochemical and immunological investigations. PMID- 2580880 TI - Ultrastructural localization of intracellular immunoglobulins in Epon-embedded human lymph nodes. An immunoelectron microscopic investigation using the immunogold staining (IGS) and the avidin-biotin-peroxidase complex (ABC) methods. AB - The ultrastructural localization of intracellular immunoglobulins on ultrathin sections of glutaraldehyde-fixed, postosmicated, and Epon-embedded human lymph nodes has been achieved using such highly sensitive immunocytochemical techniques as immunogold staining and avidin-biotin-peroxidase complex. These immunoelectron microscopic techniques allow the identification of intracellular immunoglobulins without affecting the ultrastructural morphology of the tissue, since they do not require any pretreatment of the sections with proteolytic enzymes or deresinating agents. Therefore, immunoglobulins can be precisely localized in the cell organelles; structures whose morphology is well preserved. The availability of a reliable postembedding staining procedure for the ultrastructural localization of immunoglobulins is of definite value for investigations on human lymphoid tissue, both normal and pathological. PMID- 2580881 TI - Cytokeratin polypeptide patterns of different epithelia of the human male urogenital tract: immunofluorescence and gel electrophoretic studies. AB - Intermediate filament proteins of normal epithelia of the human and the bovine male urogenital tract and of certain human renal and bladder carcinomas have been studied by immunofluorescence microscopy and by two-dimensional gel electrophoresis of cytoskeletal fractions from microdissected tissue samples. The patterns of expression of cytokeratin polypeptides differ in the various epithelia. Filaments of a cytokeratin nature have been identified in all true epithelial cells of the male urogenital tract, including renal tubules and rete testis. Simple epithelia of renal tubules and collecting ducts of kidney, as well as rete testis, express only cytokeratin polypeptides nos. 7, 8, 18, and 19. In contrast, the transitional epithelia of renal pelvis, ureter, bladder, and proximal urethra contain, in addition to those polypeptides, cytokeratin no. 13 and small amounts of nos. 4 and 5. Most epithelia lining the human male reproductive tract, including those in the epididymis, ductus deferens, prostate gland, and seminal vesicle, synthesize cytokeratin no. 5 in addition to cytokeratins nos. 7, 8, 18, and 19 (cytokeratin no. 7 had not been detected in the prostate gland). Cytokeratin no. 17 has also been identified, but in very low amounts, in seminal vesicle and epididymis. The cytokeratin patterns of the urethra correspond to the gradual transition of the pseudostratified epithelium of the pars spongiosa (cytokeratins nos. 4, 5, 6, 13, 14, 15, and 19) to the stratified squamous epithelium of the fossa navicularis (cytokeratins nos. 5, 6, 10/11, 13, 15, and 19, and minor amounts of nos. 1 and 14). The noncornified stratified squamous epithelium of the glans penis synthesizes cytokeratin nos. 1, 5, 6, 10/11, 13, 14, 15, and 19. In immunofluorescence microscopy, selective cytokeratin antibodies reveal differential staining of different groups or layers of cells in several epithelia that may relate to the specific expression of cytokeratin polypeptides. Human renal cell carcinomas show a simple cytokeratin pattern consisting of cytokeratins nos. 8, 18, and 19, whereas transitional cell carcinomas of the bladder reveal additional cytokeratins such as nos. 5, 7, 13, and 17 in various proportions. The results shows that the wide spectrum of histological differentiation of the diverse epithelia present in the male urogenital tract is accompanied by pronounced changes in the expression of cytokeratin polypeptides and suggest that tumors from different regions of the urogenital tract may be distinguished by their cytokeratin complements. PMID- 2580882 TI - Immunocytochemical demonstration of cytochrome c oxidase with an immunoperoxidase method: a specific stain for mitochondria in formalin-fixed and paraffin-embedded human tissues. AB - Cytochrome c oxidase (CO) is the terminal electron carrier of the respiratory chain and is localized exclusively in the inner membrane of the mitochondria. Using a specific rabbit antiserum against bovine heart CO, mitochondria were specifically stained in sections of formalin-fixed paraffin-embedded human tissues by an immunoperoxidase method. The intensity of the immunostaining in different human tissues correlated mainly with the number of mitochondria and abundance of mitochondrial cristae, i.e., surface area of the inner mitochondrial membrane. Mitochondrion-rich cells, such as myocardial and gastric parietal cells, had very strong cytoplasmic staining. This technique was especially useful for the specific identification of oncocytes in normal tissues and in lesions composed of oncocytes. In addition, the immunoperoxidase method for CO makes possible retrospective investigations of lesions composed of oncocytes, since routine paraffin blocks of formalin-fixed tissue are quite suitable for such studies. PMID- 2580883 TI - Optimal immunoreactivity of keratin proteins in formalin-fixed, paraffin-embedded tissue requires preliminary trypsinization. An immunoperoxidase study of various tumours using polyclonal and monoclonal antibodies. AB - The effect of preliminary trypsinization on the immunoreactivity of keratin proteins in formalin-fixed, paraffin-embedded tissues of a variety of tumors (squamous cell carcinomas, adenocarcinomas, mesotheliomas, and transitional cell carcinomas) was evaluated. Three types of trypsin (Type II and Type IX porcine trypsin and Type III bovine trypsin) and varying concentrations of trypsin were assessed. Immunoreactivity of keratin proteins was determined using rabbit anti keratin antibodies and monoclonal antibodies (combination of AE1 and AE3) and immunoperoxidase techniques. Preliminary trypsinization was mandatory for optimal immunoreactivity of keratin proteins using either polyclonal or monoclonal antibodies. Excellent results were obtained using Type II porcine trypsin at concentrations of 25 mg/dl for 30-45 min or 50 mg/dl for 20 min, at 37 degrees C. Trypsin treatment with excessive concentrations of enzyme and/or extended incubation times promoted tissue digestion and in some cases, yielded decreased immunoreactivity and altered staining patterns. PMID- 2580885 TI - Peroxisomes in fibroblasts from skin of Refsum's disease patients. AB - Skin fibroblasts were cultured from young adult patients with Refsum's disease, an inherited metabolic disorder characterized by a deficiency in oxidation of phytanic acid and by increased serum and tissue concentrations of this fatty acid. These cultures were compared to cultures of normal fibroblasts in terms of the number and distribution of peroxisomes demonstrable cytochemically in preparations incubated for catalase activity. Refsum's fibroblasts were found to contain 1-10 peroxisome profiles per 100 micron 2 of cytoplasm; the controls contained 1-2 profiles per 100 micron 2. The peroxisomes in normal fibroblasts were found in all regions of the cytoplasm. In the Refsum's material they were relatively scarce in the perinuclear region, where many of the cells showed numerous large inclusions containing lipid-like material and myelin figures. Our findings indicate that in the adult form of Refsum's disease, which is the more thoroughly studied variety, peroxisomes in fibroblasts are not diminished in number. This contrasts with a recent report concerning a case of what is thought to be an infantile form of the disorder, in which no peroxisomes were detected in a liver biopsy. If phytanic acid accumulations in the adult form are a consequence of peroxisomal defects, the defects presumably are at the level of specific enzymatic deficiencies and do not involve a generalized absence of peroxisomes. PMID- 2580884 TI - 1,25-Dihydroxyvitamin D3-induced calcium-binding protein: localization in organ cultured embryonic chick duodenum. AB - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) induces de novo biosynthesis of a specific calcium-binding protein (CaBP) in embryonic chick duodenum in organ culture. Using a highly sensitive and specific, peroxidase-antiperoxidase immunocytochemical procedure, 1,25(OH)2D3-induced CaBP in the organ-cultured duodenum was found only in the cytoplasm of absorptive cells, corresponding to its localization in rachitic chick duodenal cells after a single injection of 1,25(OH)2D3 in vivo. This observation, along with evidence correlating CaBP with calcium transport, strongly supports the use of the embryonic chick duodenal organ culture system as a physiologically relevant model of the vitamin D dependent calcium absorptive mechanism. PMID- 2580886 TI - Interstrain differences in the total RNA content in brain cells of the laboratory rat. AB - Total content of the ribosomal RNA in the cells of the frontal cerebral cortex (FCC), the septum (S), the dorsal hippocampus (DHI) and the lateral and medial hypothalamus (LHY, MHY) in adult males of the laboratory rat was determined cytophotometrically in two albino strains (i.e. in the Wistar strain (W) and in a strain with spontaneous hypertension (SHR) derived from the former) and in two pigmented strains (i.e. in the Long Evans strain (LE) and in the Brattleboro strain with spontaneous diabetes insipidus (DI) derived from the latter). The used quantitative histochemical method turned out to be very sensitive and demonstrated considerable differences in all brain structures examined. The LE strain showed higher values than the W strain in the FCC, S, DHI and LHY cells and lower ones in the MHY cells. The SHR strain was identical with the W strain from which it originated only in the FCC cells; in the S, DHI, and LHY cells it exhibited higher values, in the MHY cells lower ones. In the DI strain all values agreed with those of its original LE strain in all the areas evaluated except in the S and MHY cells where the values were lower. The data evaluated by stepwise discriminant analysis were found to be exceptional in the W strain. The data for the SHR strain were closer to the LE and DI strains, the data for the LE and DI strains intermingled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2580888 TI - Generation of primary murine CTL specific for allogeneic and xenogeneic MHC determinants upon stimulation with murine L cells transfected with class I genes. AB - This communication describes in vitro culture conditions that permit the use of MHC gene-transfected L cells as stimulators of primary CTL responses. The use of L cells as stimulators usually results in the generation of "nonspecific" anti-L cell cytotoxicity too great to permit visualization of antigen-specific CTL responses. This study demonstrates that the generation of such anti-L cell cytotoxicity can be abrogated by strategies that prevent the in vitro activation of self-Ia-restricted TH cells. These maneuvers allowed the use of L cell transfectants as stimulators of allospecific and xenospecific CTL precursors in primary in vitro mixed lymphocyte reaction cultures. PMID- 2580887 TI - Morphology and antigenicity studies on reassortant influenza (H3N2) viruses for use in inactivated vaccines. AB - Three influenza A (H3N2) reassortant whole virus vaccine strains with differing antibody-inducing capacities in hamsters were investigated morphologically and antigenically. Although initial measurements of virion circumference, from electron micrographs of vaccine preparations, suggested a relationship of small virion size with low immunogenicity, subsequent immunization with, and morphological investigation of, vaccine virions separated on sucrose gradients, failed to obtain populations whose antibody-inducing capacity clearly correlated with constituent virion density, size, morphology or integrity. However, antigenic investigation using single radial haemolysis (SRH) and monoclonal antibodies revealed significant differences in antigenic specificity between the strains. Furthermore, a series of H3N2 isolates, derived using standard reassortment procedures, also showed differences in antigenic specificity in their haemagglutination-inhibition (HI) reactions with monoclonal antibodies after five passages in allantois-on-shell cultures. Variation between these isolates and their A/Victoria parent virus could be detected using SRH and hamster sera raised against each isolate. These results demonstrate variation between candidate influenza A virus vaccine strains, all possessing the same surface (H3N2) glycoproteins, expressed as a consequence of the reassortant system used for their production. PMID- 2580889 TI - Comparison of the H-2Kb-specific cytolytic T lymphocyte receptor repertoire in Igh recombinant strains. AB - Previous studies in which the H-2Kb-specific cytolytic T lymphocytes (CTL) receptor repertoires were compared for murine strains that express different Igh alleles (C.B-20 and BALB/c) indicated that Igh-linked genes affected the composition of the expressed CTL receptor repertoire. To confirm this genetic localization, and also to individually assess the contributions of Igh-V- and Igh C-linked genes to CTL repertoire expression, the H-2Kb-specific responses of two Igh recombinant strains, BAB/14 (Igh-Va-Cb) and C.B/R3 (Igh-Vb-Ca), were analyzed. The results indicate that strains which share Igh-V (but not Igh-C) genes demonstrate significant repertoire similarities, whereas strains which share Igh-C (but not Igh-V) are no more similar than strains dissimilar throughout the Igh complex. These results are discussed in the context of the existence of a naturally occurring idiotypic network involving immunoglobulin and CTL receptors. PMID- 2580891 TI - In vivo treatment with monoclonal anti-I-A antibodies: disappearance of splenic antigen-presenting cell function concomitant with modulation of splenic cell surface I-A and I-E antigens. AB - A single injection of anti-I-Ak antibody (AB) into H-2k mice resulted in abrogation of splenic antigen-presenting cell (APC) function for protein antigen primed T cells or alloantigen-specific T cells. Spleen cells from anti-I-A treated mice are not inhibitory in cell mixing experiments when using cloned antigen-specific T cells as indicator cells, thus excluding a role for suppressor cells in the observed defect. Also, nonspecific toxic effects and carry-over of blocking Ab were excluded as causes for the defect. Experiments with anti-I-Ak Ab in (H-2b X H-2k)F1 mice showed abrogation of APC function for T cells specific for both parental I-A haplotypes. In homozygous H-2k mice, anti-I-Ak treatment not only abrogated APC function for I-Ak-restricted cloned T cells but also for I AekE alpha k-restricted cloned T cells. FACS analysis of spleen cells from anti-I Ak-treated (H-2b X H-2k)F1 mice revealed the disappearance of all Ia antigens (both I-A and I-E determined), whereas the number of IgM-bearing cells was unaffected. The reappearance of APC function with time after injection was correlated with the reappearance of I-A and I-E antigen expression. In vitro incubation of spleen cells from anti-I-A-treated mice led to the reappearance of Ia antigen expression and APC function within 8 hr. Thus, it appears that B cells (as determined by FACS analysis) and APC (as determined by functional analysis) behave similarly in response to in vivo anti-I-A Ab treatment. We interpret these findings as suggesting that in vivo anti-I-A treatment temporarily reduces the expression of Ia molecules through co-modulation on all Ia-bearing spleen cells, thereby rendering them incompetent as APC. Such modulation of Ia molecules does not occur when spleen cells are incubated in vitro with anti-I-A antibodies. These results imply that a primary defect purely at the level of APC in anti-I-A treated mice may be responsible for the observed T cell nonresponsiveness when such mice are subsequently primed with antigen. PMID- 2580890 TI - Influence of the H-2u haplotype on immune function in F1 hybrid mice. I. Antigen presentation. AB - Previously, we reported that myelin basic protein (MBP) peptide 1-37 contains an encephalitogenic epitope for PL/J mice, and MBP peptide 89-169 is encephalitogenic for SJL/J mice. (SJPL)F1 hybrid mice do not respond to immunization with these peptides in a co-dominant manner because the encephalitogenic response to peptide 1-37 dominates. To examine this phenomenon more closely, we tested the ability of MBP-primed parental or F1 T cells to respond to MBP or MBP peptides in the context of PL, SJL, or F1 antigen presenting cells (APC). It was found that the F1 T cells responded to either the protein or the peptides when these were presented in the context of F1 or PL APC. However, F1 T cells would not respond to MBP in the context of SJL APC, although the latter cells were functionally intact. This effect was not antigen-specific because SJL APC would not present ovalbumin or PPD to primed F1 T cells. F1 T cells from mice immune to the strongly antigenic bacterium Listeria monocytogenes responded to bacterial antigens presented by SJL APC, although at a significantly lower level compared to the results obtained when these antigens were presented by F1 or PL APC. This finding implied that unbalanced antigen presentation was a quantitative rather than a qualitative phenomenon. When F1 hybrid mice from other strain combinations were tested, a similar effect was observed whenever one of the parental strains was PL/J. This effect was mapped to the MHC in MHC-congenic B10 mice. PMID- 2580893 TI - Studies on the induction of tolerance to alloantigens. I. The abrogation of potentials for delayed-type-hypersensitivity response to alloantigens by portal venous inoculation with allogeneic cells. AB - The present study investigates the effect of portal venous (p.v.) administration of allogeneic cells on the capacity of delayed-type-hypersensitivity (DTH) reactivity to alloantigens. BALB/c mice were inoculated with C3H/He spleen cells via intravenous (i.v.) or p.v. route. Intravenous injection of C3H/He spleen cells into BALB/c mice resulted in appreciable DTH responses to C3H/He alloantigens. In contrast, p.v. inoculation of the same number of C3H/He cells not only failed to induce any significant anti-C3H/He DTH responses but also abolished the capability of the animals to develop DTH responses as induced by subcutaneous (s.c.) immunization with C3H/He spleen cells. Such suppression was alloantigen-specific, since p.v. inoculation of C3H/He spleen cells resulted in selective inhibition of anti-C3H/He DTH potential without suppressing DTH responses to C57BL/6 alloantigens. This tolerance was rapidly inducible and long lasting. When spleen cells from tolerant mice were transferred i.v. into 600 R X irradiated syngeneic recipient mice alone or together with normal BALB/c spleen cells, these tolerant spleen cells themselves failed to induce DTH responses but did not exhibit any suppressive effect on the generation of DTH responses induced by normal spleen cells co-transferred. These results indicate that tolerance was not necessarily associated with the induction of suppressor cell activity but rather was associated with the elimination or functional impairment of clones specific for alloantigens. The results are discussed in the context of a) the role of the liver in immune responses, b) cellular mechanisms underlying the tolerance induction, and c) potential application of this approach to the future transplantation immunology. PMID- 2580892 TI - Enhanced activation of a T cell line specific for acetylcholine receptor (AChR) by using anti-AChR monoclonal antibodies plus receptors. AB - Immune complex-mediated regulation of the immune response has been studied by using T cell lines and monoclonal antibodies (MAb), both specific for the acetylcholine receptor (AChR). Rat T lymphocytes bearing the W3/25 phenotype and specific for AChR from Torpedo californica have been propagated in vitro for nearly 1 yr. These T cells proliferate in response to optimal concentrations of AChR presented by irradiated syngeneic thymus cells. At suboptimal concentrations of antigen there is little activation of the T cell line. We report here that the addition of small amounts of anti-AChR MAb produces dramatic stimulation of the T cell lines at suboptimal doses of AChR. Enhanced activation depends on the isotype and not the fine specificity of the MAb that are used. The observed phenomenon is antigen specific, and in fact, the immune complexes may actually suppress the proliferative response of irrelevant T cells to some extent. The MAb plus antigen are rapidly bound to the surface of the antigen-presenting cell, which we have shown is the dendritic cell. PMID- 2580894 TI - Homologous monoclonal antibodies specific for alpha 1-3 dextran stimulate polyclonal proliferation of Lyb-5+ B cells. AB - In this paper we describe the polyclonal blast response induced in nonimmune murine splenocytes by two homologous alpha 1-3 dextran-binding myeloma protein, J558 and MOPC104E. This stimulation appears to be independent of MHC or IgCh gene complex control, and proceeds entirely in a T-dependent fashion. The responding B cell population appears to belong to the more mature Lyb-5+ subset. This response was elicited by several independently prepared batches of J558 and MOPC104E, each of which was conclusively shown to be free of endotoxin contamination. Experiments are presented that suggest that this stimulation is being mediated via the Fab portion of these two myeloma proteins, in particular, a shared IdX, rather than through their Fc. PMID- 2580895 TI - Induction of nonspecific cytotoxicity by monoclonal anti-T3 antibodies. AB - The effects of monoclonal anti-T3 antibodies on the effector phase of cytotoxic T lymphocytes (CTL) were studied with respect to antigen-specific and antigen nonspecific lysis of different target cells. Anti-T3 antibodies inhibited the antigen-specific lysis by CTL generated in mixed lymphocyte cultures (MLC), but they concomitantly augmented the nonspecific killing of third-party cells such as the cell lines Daudi, Raji, and K562. This nonspecific cytotoxicity was induced by various anti-T3 antibodies, whereas antibodies reactive with other antigens expressed on the cytotoxic effector cells lacked any such activity. Anti-T3 antibodies induced nonspecific cytotoxicity only when activated T cells, obtained by primary MLC, by repeated restimulation, or after cloning, were used. The antibodies had no effect on unstimulated peripheral T lymphocytes or thymocytes. The inhibition of the antigen-specific lysis and the induction of nonspecific lysis by anti-T3 was dose dependent, and both effects occurred at the same concentration range of anti-T3. F(ab')2 fragments of anti-T3 inhibited the specific lysis but were not able to induce cytotoxic activity, indicating that this induction is an Fc-dependent process. When different target cells were tested, only Fc receptor-positive cells were susceptible for this nonspecific cytotoxicity. Thus, anti-T3 antibodies have a dual effect on effector CTL: they inhibit antigen-specific lysis and concomitantly induce nonspecific lysis in an Fc-dependent way. PMID- 2580896 TI - Correlation between the inducible keratinocyte expression of Ia and the movement of Langerhans cells into the epidermis. AB - A direct correlation between the induced expression of Ia by the host keratinocytes and the infiltration of donor Langerhans cells (LC) into the epidermis was demonstrated in athymic (nude) BALB/c mice that received an adoptive transfer of lymphoid cells from normal semi-syngeneic donors. Neither keratinocyte expression of Ia nor donor LC movement into the epidermis was observed in BALB/c recipients of lymphoid cells from allogeneic C3H nude mice. Further evidence for this relationship was provided by experiments in which the keratinocytes of BALB/c nude mice were induced to express Ia by the injection of normal mouse serum (NMS). By this procedure it was shown that LC precursors derived from allogeneic C3H nude donors were able to infiltrate the epidermis when adoptively transferred into BALB/c nude recipients whose keratinocytes had been induced to express Ia by the simultaneous injection of NMS. These findings suggest that keratinocytes through their expression of Ia may function to facilitate the movement of LC into the epidermis. PMID- 2580897 TI - In vitro regulation of the pathogenic autoantibody response of New Zealand black mice. I. Loss with age of suppressive activity in T cell populations. AB - An investigation of the regulation of specific anti-self responses was initiated with the development of an in vitro system in which spleen cells from NZB mice were stimulated by syngeneic mouse erythrocytes (MRBC) to produce MRBC-specific autoantibody-secreting cells. The response was measured by a modification of the focus-forming cell (FFC) assay, which enumerates cells secreting IgG, which specifically bind MRBC. Spleen cells from 9- to 12-mo-old NZB mice developed MRBC specific FFC after 3 to 5 days in culture with MRBC. Few FFC were detected in the absence of MRBC in culture. Spleen cells from young (1- to 4-mo-old) NZB mice developed few if any FFC. Spleen cell populations containing T cells from young NZB mice suppressed this anti-MRBC response, whereas B cell populations from these young mice did not. In contrast, spleen cells, including T cell-enriched populations from old, Coombs'-positive mice were not capable under the same conditions of producing equivalent suppression of this in vitro autoimmune response. These data suggest that a population of suppressor T cells that may control the autoimmune anti-MRBC response in young NZB mice is lost, or else its activity is masked in old NZB mice that are actively producing anti-MRBC antibody. PMID- 2580898 TI - Inhibition of IL 2-dependent proliferation of rat T lymphoblasts by the monoclonal antibody ART62 which reacts with MHC class 1 antigens. AB - During the course of studies designed to obtain monoclonal antibodies (mAb) that recognize the rat interleukin 2 receptor, a mouse IgG1 mAb (ART62) was identified which inhibits the interleukin 2 (IL 2)-dependent proliferation of rat T lymphoblasts without affecting the binding of IL 2 to such cells. In order to characterize the cell surface components that react with the mAb ART62, T lymphoblasts were surface-labeled with 125I, and the radioactive molecules were immunoprecipitated by the antibody analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The mAb ART62 precipitated two major components of 48,000 m.w. and 12,000 m.w., respectively, which were different from those which react with the anti-IL 2-receptor antibody ART18, a molecule of 50,000 to 55,000 m.w. Sequential immunoprecipitation studies revealed that the mAb ART62 reacts with the MHC class 1 antigen that reacts with the classical anti-rat MHC class 1 mAb OX18, and vice versa. In contrast to the mAb ART62, OX18 that does not affect and several other mAbs known to inhibit the rat MLR failed to inhibit IL 2-dependent proliferation of rat T lymphoblasts. In contrast to the anti-IL 2 receptor antibody ART18, ART62 effectively inhibited IL 2-driven proliferation even when added to cells already committed to proliferate by IL 2-IL 2 receptor interaction. These data raise the possibility that MHC class 1 antigens could be involved in the chain of reactions mediating the signals required for cell proliferation. PMID- 2580899 TI - Role of BCGFII in the differentiation to antibody secretion normal and tumor B cells. AB - This report describes the effects of B cell growth factor (BCGFII) and other lymphokines in the differentiation of normal and tumor B cells. We compared BCL1 tumor B cells, normal B cells giving rise to a polyclonal response without the intentional addition of antigen, and an antigen-driven, SRBC-specific response. BCL1 tumor B cells gave maximum PFC responses when partially purified BCGFII was added or when suboptimal doses of BCGFII were mixed with one of several putative terminal differentiation factors we call B cell differentiation factors BCDF. IFN gamma was not active as any of these factors. Maximum polyclonal responses of B cells were seen when either IL 2 or BCGFII were mixed with BCDF. In contrast, SRBC-specific responses showed a strict requirement for IL 2, and BCGFII and BCDF synergized with IL 2 to give a maximum response. The involvement of BCGFII in all of these responses suggests that BCGFII acts as a growth factor for a population of B cells that has differentiated much of the way towards Ig secretion, and that many B cells become responsive to this growth factor. In addition, the fact that different lymphokine requirements were seen in the different experimental systems raises the possibility that there are multiple pathways to Ig secretion, and suggests that different subpopulations of B cells defined either by different lineages or by different stages of development within a single lineage have requirements for distinct lymphokines that regulate their growth and differentiation. PMID- 2580900 TI - Augmentation of mouse natural killer cell activity by LS 2616, a new immunomodulator. AB - The quinoline-3-carboxamide LS 2616 administered to mice in drinking water increased spontaneous cytotoxicity against YAC-1 cells in a dose-dependent manner. The enhancement of spontaneous cytotoxicity was found to be mediated by NK cells, as judged by their lack of adherence to nylon wool columns, relative resistance to treatment with antibodies to Thy-1.2 and complement, and almost total abrogation after depletion of asialo-GM1+ cells. Enhancement of NK activity was evident after 2 days of treatment, was maximal after 4 days, and remained elevated during the 14-day exposure period studied. NK activity returned to control levels 4 days after cessation of treatment. NK activity was significantly increased in spleen, peripheral blood, lymph nodes, and bone marrow of LS 2616 treated mice, while activity in peritoneal exudate cells and thymus remained low. LS 2616 was able to elevate NK activity in several mouse strains studied, including mice homozygous for the beige gene. Serum interferon levels were not increased during treatment with LS 2616. Combined injection of the interferon inducer Poly I:C and LS 2616 did not increase NK activity above that of animals injected with Poly I:C alone. However, Poly I:C, in contrast to LS 2616, increased NK activity in peritoneal exudate cells. Studies at the single cell level revealed that LS 2616 increased NK activity by increasing the number of lytically active cells via recruitment of new target-binding cells and not by increasing the lytic activity of pre-existing binders. PMID- 2580901 TI - Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor. AB - Repeated immunization of normal C57L/J (H-2b) mice with peripheral T cells from BALB.B (H-2b) mice results in the production of antibodies which react with the T cell receptor. A monoclonal antibody-producing hybridoma, F23.1, was isolated from immunized C57L/J mice showing this property. This monoclonal antibody recognizes approximately 25% of peripheral T cells in BALB mice. It stains approximately the same fraction of T cells and precipitates the same heterodimer as the rat monoclonal antibody described previously that was made against isolated receptor material. The allotypic determinant recognized by this monoclonal antibody is present in most common laboratory strains (BALB, C57BL, CBA, A, DBA, C3H) and is absent in C57L, C57BR, and SJL mice. Sorting peripheral T cells from BALB.B or (SJL X BALB/c)F1 mice for the F23.1+ and F23.1- subsets revealed that both populations contain approximately the same CTL precursor frequency for alloantigen. Thus, the T cell receptor allotype defined by F23.1 is present on CTL. Furthermore, cytotoxicity mediated by an F23.1+ CTL line could be blocked specifically by the F23.1 monoclonal antibody. Under appropriate conditions, the monoclonal antibody F23.1 bound to Sepharose 4B beads can induce resting peripheral T lymphocytes of allotype-positive strains to proliferate. PMID- 2580902 TI - Functional studies on the role of I-A molecules expressed by the antigen-specific T suppressor cell clone HF1. AB - The antigen-specific T suppressor (Ts) cell clone HF1 (Thy-1.2+, I-Ak+, I-Ek+) was isolated from a CBA/J mouse tolerized to low doses of bovine serum albumin (BSA), and a subclone was adapted to grow in the absence of antigen-presenting cells. The functional role of the I-Ak molecules endogenously expressed by HF1 Ts cells was analyzed by using anti-I-Ak monoclonal antibodies (mAb) in attempts to block the antigen-induced proliferation of these cells. Among a panel of anti-I Ak mAb tested, only the H118-49 mAb directed against the private determinant Ia.m1 blocked BSA-induced proliferation. The data presented here suggest a selective regulatory role of membrane-bound I-Ak molecules in the antigen-induced signal transmission. PMID- 2580903 TI - p65: A C3b-binding protein on murine cells that shares antigenic determinants with the human C3b receptor (CR1) and is distinct from murine C3b receptor. AB - Affinity-purified rabbit antibody to the human C3b receptor (CR1) cross-reacted with an antigen that was expressed on murine splenocytes, lymph node cells, thymocytes, peritoneal macrophages, erythrocytes, and L929 cells, as assessed by flow cytofluorographic analysis of indirectly stained cells. The cell surface antigen recognized by antihuman CR1 had a Mr of 60,000 to 65,000 on each cell type, and the cross-reactive epitope(s) was sensitive to reduction with dithiothreitol but not to oxidation with NaIO4. Analysis by affinity chromatography of murine splenic B lymphocytes identified two cell surface proteins capable of binding to guinea pig C3b (C3bgp). The larger polypeptide had a Mr of 210,000, was not present in L929 cells, and may represent the murine CR1. The smaller polypeptide of 65,000 Mr was also present on L929 cells and was shown to constitute the cross-reactive antigen. Adsorption of detergent lysates of L929 cells with C3bgp-Sepharose depleted by 44% the antigen recognized by anti-human CR1; the C3bgp-binding protein and the cross-reactive antigen exhibited similar patterns on two-dimensional gel electrophoresis; and the isolated C3b-binding protein could be immunoprecipitated with anti-human CR1. Thus, the murine cell surface protein, termed p65, that is antigenically cross-reactive with human CR1 shares a capacity for binding to C3b in its detergent-solubilized form but is distinct from murine CR1 in its lower Mr, wider cellular distribution, and inability to mediate the adherence of C3b-coated particles in its native, membrane-associated form. PMID- 2580904 TI - Increased phosphatidylinositol metabolism is an important but not an obligatory early event in B lymphocyte activation. AB - The phosphatidylinositol (PI) response has been implicated in membrane signaling and cell activation. The role of phospholipid metabolism among the early events in B cell activation has not been clear. We have treated murine B cells with anti Ig antibody and lipopolysaccharide (LPS) and have found that, although anti-IgM induces the PI response, LPS does not. The increase in metabolic labeling of PI is specific to PI, and not the phosphatidylinositols. Anti-IgM unresponsive B cells from CBA/N mice, which may correspond to a specific functional subpopulation of normal B cells, do not increase PI metabolism in response to anti-IgM, nor do they undergo blastogenesis or DNA synthesis. Moreover, when these deficient B cells are given a stimulus sufficient to drive them into S (LPS + anti-IgM), there is still no corresponding activation of PI metabolism. These results are consistent with a two-signal model of xid B cell activation by anti IgM. One very early signal primes the cells but does not induce the PI response. A second early signal is supplied by LPS. This signal sustains cells in the activated state, allowing them to receive yet other signals to proceed through G1 and progress further along the cell cycle. A similar sequence of events may occur in the normal B cell, with the first signal provided by priming with anti-IgM, and the second signal, the PI response, supported by a sufficiently high dose of anti-IgM to induce PI turnover and maintain the cell in G1. PMID- 2580905 TI - Evidence for a beta-adrenoceptor-mediated regulation of human natural killer cells. AB - Pretreatment of lymphocytes (16 hr, 37 degrees C) with adrenaline at final concentrations of 10(-7) to 10(-9) M, followed by removal of the drug, increased natural killer (NK) cell activity vs K562 leukemic cells in a 4-hr 51Cr-release assay. The most efficient concentration of adrenaline was 10(-8) M; mean increase of NK activity over base-line activity for all donors examined was 30%. However, the individual response to adrenaline pretreatment was variable; in some donors, the effect was equal to maximal interferon (IFN) stimulation. Effects of adrenaline pretreatment were consistently reduced to base-line activity by co incubation with the nonselective beta-adrenoceptor antagonist propranolol at 100 fold higher concentrations. The enhancing effect of adrenaline (10(-8) M) pretreatment was also observed after 1-hr pretreatment; this effect was prevented by simultaneous incubation with propranolol but was not affected by dex propranolol. Direct addition of adrenaline to lymphocyte/target cell mixtures was inhibitory at 10(-6) M adrenaline concentration. The inhibitory effect of adrenaline in this assay was again completely prevented by propranolol and unaffected by dex-propranolol. The observed stimulatory effect of adrenaline pretreatment could not be ascribed to IFN production. Data presented indicate a dual effect of adrenaline on NK cell activity and suggest both a positive and a negative beta-adrenoceptor-mediated regulation of human NK cells. PMID- 2580906 TI - Vaccination against the intracellular bacterium Listeria monocytogenes with a clonotypic antiserum. AB - The T cell clone 26.1.1, which confers specific protection against the intracellular bacterium Listeria monocytogenes, was fused to BW 5147. The resulting T cell hybridoma, TLm1, could be stimulated to secret interleukin 2 by antigen plus accessory cells or concanavalin A. Stimulation was specific for an epitope expressed by L. monocytogenes EGD but not ATCC 19114 and was H-2I-A restricted. Antisera against TLm1 were raised in syngeneic mice and tested for their capacity to block TLm1 responses. Two antisera were identified that blocked antigen but not concanavalin A stimulation of TLm1 and did not affect antigen stimulation of similar but not identical L. monocytogenes-specific T cell hybridomas. Hence, these antisera had clonotypic activity. When these antisera were administered subcutaneously in complete Freund's adjuvant, mice were protected against a subsequent L. monocytogenes infection. Protection was antigen specific and H-2 nonrestricted. These findings suggest the feasibility of clonotypic antibodies for vaccination against intracellular bacterial infections. PMID- 2580907 TI - Specific Schistosoma mansoni rat T cell clones. I. Generation and functional analysis in vitro and in vivo. AB - In an attempt to determine the role of schistosome-specific T cells in the immune mechanisms developed during schistosomiasis, Schistosoma mansoni-specific T cells and clones were generated in vitro and some of their functions analyzed in vitro and in vivo in the fischer rat model. The data presented here can be summarized as follows: a) Lymph node cells (LNC) from rats primed with the excretory/secretory antigens-incubation products (IPSm) of adult worms proliferate in vitro only in response to the homologous schistosome antigens and not to unrelated antigens (Ag) such as ovalbumin (OVA) or Dipetalonema viteae and Fasciola hepatica parasite extracts. b) After in vitro restimulation of the primed LNC population with IPSm in the presence of antigen-presenting cells (APC) and maintenance in IL 2-containing medium, the frequency of IPSm-specific T cells is increased and the T cells can be restimulated only in the presence of APC possessing the same major histocompatibility complex (MHC) antigens. c) Following appropriate limiting dilution assays (LDA) (1 cell/well), 10 IPSm-specific T cell clones were obtained, and two of four maintained in culture were tested for their helper activity because they expressed only the W3/13+ W3/25+ surface phenotypes. d) The two highly proliferating IPSm-specific T cell clones (G5 and E23) exhibit an IPSm-dependent helper activity, as shown by the increase in IgG production by IPSm-primed B cells. e) IPSm-T cell clone (G5) as well as IPSm-T cell lines when injected in S. mansoni-infested rats can exert an in vivo helper activity, which is characterized by an accelerated production of IgG antibodies specific for the previously identified 30 to 40 kilodaltons (kd) schistosomula surface antigens (Ag). As recent studies have demonstrated that rat monoclonal antibodies recognize some incubation products of adult S. mansoni as well as one of the 30 to 40 kd schistosomula surface antigens, and taking into account the fact that the T cell clones here studied were restimulated either with IPSm or with schistosomulum Ag, it appears that such IPSm-specific T cell clones could be involved in the concomitant immunity mechanisms. PMID- 2580908 TI - Characterization of the human newborn response to herpesvirus antigen. AB - An investigation was made into the human newborn cellular response to herpes simplex virus type 1 (HSV), cytomegalovirus (CMV), and varicella zoster virus (VZV) to understand more about the nature of the neonate's susceptibility to overwhelming infection by these viruses. Newborn mononuclear cells sustained the proliferation in culture of maternal (i.e., haplotype-matched) T cell blasts with specificity for HSV, CMV, or VZV (p less than 0.05). This is evidence for intact antigen-processing capability by newborn monocytes. The response of the maternal T cell blasts appeared to be HLA-haplotype-restricted as suggested by experiments in which maternal T cell blasts were limited in number. Our culture conditions elicited responses predominantly from the T4+ lymphocyte subset. A low frequency of herpesvirus-specific T4+ lymphocytes in newborn blood might contribute to deficient viral immunity, so we evaluated the virus-specific T cell responding frequency in human newborns in limiting dilution cultures. We were unable to find a herpesvirus-specific responder cell frequency greater than 1:1,400,000 in nonimmune newborns. Three of seven adults who had no serum antibody to CMV had a CMV responder cell frequency (RCF) of 1:100,000 to 1:200,000. The RCF to HSV in immune children, ages 18 mo to 12 yr, and adults, ages 13 to 80 yr, ranged from 1:14,000 to 1:18,000. We conclude that newborn monocyte processing of herpesvirus antigen is intact, that T cell RCF is low in neonates, and that immunity to HSV after infection outside the newborn period results in comparable RCF between adults and children. PMID- 2580909 TI - Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). VI. T cell fine specificity. AB - In the companion paper it was demonstrated that the T cell proliferative response to HBsAg was controlled by I region genes as was previously shown for in vivo anti-HBs production. In this paper, the structural requirements for T cell recognition of HBsAg were compared with B cell (antibody) recognition of HBsAg. Secondly, we attempted to map determinants on HBsAg required for activation of HBsAg-primed T cells, and we examined the influence of I region genotype on the observed T cell antigenic fine specificity. The results of these studies indicate clear differences between T cell and B cell recognition of HBsAg. T cell activation required significantly less native structure as compared with antibody binding to HBsAg. Reduced and alkylated HBsAg, the subunit polypeptide P25, tryptic fragments of P25, and synthetic peptide analogues of HBsAg were all capable of eliciting a T cell proliferative response, whereas these "denatured" forms of the antigen bind anti-HBs marginally or not at all. Furthermore, the results suggest that T cell recognition sites on HBsAg do not necessarily overlap with B cell recognition sites. Examination of T cell fine specificity in a series of H-2 congenic strains, with the use of HBsAg, P25, tryptic fragments of P25, and synthetic peptides, revealed multiple T cell recognition sites on HBsAg, and the particular site(s) recognized is dependent on the H-2 genotype of the responding strain. Finally, preliminary results indicate that the specificity of human, HBsAg-primed T cells appear to be variable among individuals. PMID- 2580911 TI - The importance of antibody affinity in the performance of immunoassays for antibody. PMID- 2580912 TI - A method for binding specificity analysis of anti-DNA autoantibodies in SLE. AB - A pattern of differential binding between an NZB/NZW mouse-derived monoclonal anti-ssDNA antibody, V'D2, and restriction fragments of plasmid pBR322 DNA was shown by electrophoresis of the fragments through a denaturing agarose gel followed by their transfer onto nitrocellulose membrane and subsequent reaction of the immobilized DNA with the antibody and 125I-protein A. The antibody showed preferential binding to a 328 base pair Alu I + Hinf I fragment (denoted FD) (AT content, 60%), compared with the other fragments (AT contents, 40-56%). In dot blot assays the antibody bound only to poly(dT) and poly(dA,dT), failing to bind to other synthetic deoxyribopolynucleotides even at the highest concentration tested (300 ng). In competition experiments, the ability of unlabeled DNA to inhibit binding of V'D2 to FD increased with AT content of the DNA. It is concluded that V'D2 has preference for AT-rich DNA. In addition, poly(dA,dT) inhibited binding to a greater extent than either poly(dA) or poly(dT), indicating that base sequence may be important in defining the antigenic determinant. The method, appropriately modified, may be applicable to a wide range of natural nucleic acids and monoclonal antibodies, allowing detection and isolation of specific DNA fragments for detailed studies of antigenic determinants. PMID- 2580910 TI - Human T cell leukemia/lymphoma virus-infected antigen-specific T cell clones: indiscriminant helper function and lymphokine production. AB - The ability of human T cell leukemia/lymphoma virus (HTLV)-I to alter the function of infected T lymphocytes was examined directly by investigating the properties of an antigen-specific T cell clone before and after transformation with HTLV-I. Following infection, the T4 antigen-specific clone manifested a tenfold increase in its surface interleukin 2 (IL 2) receptor (Tac) density and acquired the viral determinants p19, p24, and 4D12 not present in the uninfected clone. Prior to infection, the T cell clone responded to antigen stimulation in the presence of histocompatible antigen-presenting cells with proliferation and secretion of multiple lymphokines, including IL 2, B cell growth factor (BCGF), B cell differentiation factor (BCDF), and interferon-gamma (IFN-gamma). Following infection, the T cell clone both proliferated and produced constitutively three of these lymphokines (BCGF, BCDF, and IFN-gamma) in the absence of accessory cells or antigen. Co-cultivation with any accessory cells regardless of histocompatibility resulted in increased proliferation and lymphokine production. IL 2 production by the HTLV-I-transformed cell, however, could not be detected. Similarly, the uninfected clone was able to provide B cell help for Ig production only when stimulated with both histocompatible cells and antigen. In contrast, the infected cell provided T cell help to B cells in an unregulated manner, independent of antigen or histocompatibility. Thus, functions such as the induction of proliferation, B cell help, and lymphokine production, which are finely regulated in uninfected antigen-specific T cell clones, became indiscriminant after HTLV-I infection. PMID- 2580913 TI - Discrimination of epitopes identified by monoclonal antibodies by competitive binding to nitrocellulose bound antigens. AB - A new method is described for determining the distribution of epitopes identified by monoclonal antibodies. The method utilizes nitrocellulose membranes as a solid support for antigens which are rapidly adsorbed to nitrocellulose by vacuum blotting and then used in competitive antibody binding assays. The distribution of epitopes is established by the reciprocal cross-blocking of radiolabeled antibody by increasing concentrations of unlabeled antibody. When unlabeled antibody does not block the binding of labeled antibody to antigen, the 2 antibodies recognize distinct epitopes. When unlabeled antibody blocks the binding of labeled antibody to antigen, the 2 antibodies recognize the same epitope. The method is rapid, sensitive and should be applicable to screening monoclonal antibodies to any epitope. PMID- 2580914 TI - Serum factor-dependent resistance of Haemophilus influenzae type b to antibody to lipopolysaccharide. AB - Haemophilus influenzae type b (Hib) grown in broth is much more sensitive to killing by antibody to lipopolysaccharide (LPS) and complement than is Hib in bacteremic rats; upon brief incubation with low-molecular-weight components of plasma or serum, however, broth-grown cells are phenotypically converted to a resistance resembling that in vivo. This conversion was found to consume a limiting factor in serum filtrate, to require protein synthesis, and to occur independently of the presence of capsule. Less antibody to LPS bound to cells of the resistant (Res) phenotype than to cells of the sensitive (Sen) phenotype. In electrophoretic analysis the mobility of LPS bands was identical, but the staining density of the LPS bands extracted from Res cells (with phenol-water) was two-to fourfold greater than from an equal number of Sen cells. A similar differential was found in an immunologic assay of LPS in the extracts. Thus, Hib in the Res phenotype (and perhaps Hib in vivo) contains more LPS than Hib in the Sen phenotype, but its LPS appears less accessible to antibody. PMID- 2580915 TI - Antibody response in human nocardiosis: identification of two immunodominant culture-filtrate antigens derived from Nocardia asteroides. AB - An ammonium sulfate precipitate derived from a culture filtrate of Nocardia asteroides contained 20-30 protein subunits, as identified by gel electrophoresis. Western blot analysis of these proteins (obtained from serum samples from patients with systemic nocardiosis) revealed that all of the 17 samples reacted with a subunit of a protein with an apparent molecular weight of 55,000 and that 11 of the 17 samples reacted with a subunit with a molecular weight of 31,000. In contrast, only two of 25 serum samples obtained from healthy controls or patients hospitalized without nocardial or mycobacterial disease reacted with these subunits. Sera from 21 patients infected with Mycobacterium tuberculosis, a historically troublesome cross-reactive group, failed to react with either the 55,000 or the 31,000 molecular weight subunit. The presence of only two protein subunits that reacted with sera from humans with nocardiosis suggests that these molecules may have use as diagnostic reagents or probes of the immunologic reaction to Nocardia. PMID- 2580916 TI - Viral-bacterial pneumonia in calves: effect of bovine herpesvirus-1 on immunologic functions. AB - The temporal relation between a lung infection with bovine herpesvirus-1, suppression of some immune functions, and susceptibility to secondary bacterial infection resulting in fibrinous pneumonia prompted a study to determine the mechanism(s) involved in the apparent immunosuppression. In six independent experiments employing from five to 40 calves, we studied the immunologic parameters of migration of and superoxide anion production by polymorphonuclear neutrophils, lectin-induced lymphocyte proliferation, interleukin-2 production, natural cytotoxicity, interferon and antibody formation, as well as complement activation and hematologic parameters. Chemotaxis of polymorphonuclear neutrophils, natural cytotoxicity, and mitogen response of peripheral blood leukocytes were depressed, whereas superoxide anion generation by polymorphonuclear neutrophils was transiently increased and interleukin-2 production was only marginally affected. The assumption that virus-induced interferon might be a common cause for the various changes could not be substantiated. However, the results did suggest that mechanisms other than lack of T helper cell activity, accessory cell activity of macrophages, or development of suppressor T cells were the cause of suppressed mitogen responses. None of the immunologic parameters appeared to have consistent prognostic value with respect to outcome of the infection. PMID- 2580917 TI - Cytomegaloviral infections in infant-toddler centers: centers for the developmentally delayed versus regular day care. PMID- 2580919 TI - Adsorption of poly rI:rC on cell membrane participating and nonparticipating in interferon induction. AB - PR-RK cells, which were derived from RK-13 cells by repeated treatment with a copolymer of polyriboinosinic acid and polyribocytidylic acid (poly rI:rC), were resistant to the cytotoxic effect of poly rI:rC, and could not produce interferon when exposed to poly rI:rC alone. These characteristics of PR-RK cells have not reversed for more than 40 passages of the cells in medium without poly rI:rC. Poly rI:rC was adsorbed on PR-RK cells at a rate of 60 to 70% of its adsorption to RK-13 cells. On the other hand, PR-RK cells could produce a low level of interferon when they were induced by a poly rI:rC-DEAE dextran complex, by poly rI:rC and metabolic inhibitors (superinduction), by poly rI:rC and pretreatment with interferon (priming), and by Newcastle disease virus. Interferon production in RK-13 cells in response to poly rI:rC or poly rI:rC-DEAE dextran complex was inhibited by pretreatment of the cells with anti-RK-13 cell serum and anti-RK-13 cell serum absorbed with PR-RK cells. These results suggest that PR-RK cells are deficient in the receptor for poly rI:rC, and that poly rI:rC can adsorb onto the cell membrane nonspecifically, acting as a weak inducer when transcriptional control in cells is affected by superinduction or priming. Only about 30% of the poly rI:rC adsorbed on RK-13 cells may be specific binding, participating in normal interferon induction. PMID- 2580918 TI - Circulating interferon and clinical symptoms in Colorado tick fever. PMID- 2580920 TI - Purification of chick interferon by zinc chelate affinity chromatography and sodium dodecylsulfate-polyacrylamide gel electrophoresis. AB - An improved purification method for chick interferon from the allantoic fluid of embryonated chick eggs is described. Interferon prepurified by perchloric acid treatment, zinc acetate precipitation, and chromatography on SP-Sephadex C-25 was further enriched by column chromatography on zinc chelate. Analysis on sodium dodecylsulfate polyacrylamide gel electrophoresis of the interferon preparation with a specific activity of 8 X 10(5) units/mg protein shows that the major antiviral activity migrated in a broad band in the range of 20-29 kD molecular weight. Several protein bands were stainable with Coomassie blue and silver nitrate in this molecular weight range. Between 80 and 95% of the total protein charged to the gel could be removed from the interferon containing fractions by sodium dodecylsulfate polyacrylamide gel electrophoresis. PMID- 2580921 TI - Proliferation and interferon production in whole blood samples and isolated lymphocyte preparations. AB - To establish a method for the evaluation of immunological parameters in small blood samples, a whole blood technique was developed for the estimation of mitogen induced cell proliferation and interferon (IFN) production. The results obtained were compared with data using isolated peripheral blood lymphocytes (PBL). Mixtures of heparinized whole blood and culture medium or equal numbers of PBL of healthy volunteers or of patients were cultured with the mitogens concanavalin A, phytohemagglutinin, pokeweed mitogen or the monoclonal antibodies OKT3 and anti-Leu-4. Cell proliferation as measured by 3H-thymidine incorporation and interferon production were found to be of higher magnitude in the whole blood assay. The only situation in which results were similar was pokeweed mitogen induced cell proliferation. Since in the whole blood assay the cell populations are present in their natural distribution, this test system may reflect the in vivo situation better than the test using isolated lymphocytes. Furthermore, our data indicate that whole blood samples may be used clinically for the evaluation of different immune parameters, as data on a limited number of patients with Hodgkin's disease have shown. PMID- 2580922 TI - Studies on cell binding and internalization of human lymphoblastoid (Namalva) interferon. AB - The binding of iodinated human lymphoblastoid Namalva interferon to Namalva cells, to a human fibroblast cell strain (FS11), and to a bovine kidney cell line (MDBK) was characterized. Scatchard analysis of the binding data indicated the presence of about 1000-2000 receptors per cell and dissociation constants of the order of 0.1 to 0.01 nM. Two subspecies of Namalva interferon (16 K and 20 K), which differ in their antiviral activity toward bovine and human cells, were found to bind with the same affinity toward bovine MDBK cells but to differ in their affinity to human cells. Experimental results indicated that at 37 degrees C the bound interferon is internalized within 15 min after binding to Namalva cells, and then degraded in the lysosomes. Exposure of Namalva cells to interferon resulted in a 40% reduction of the number of cell surface receptors (down-regulation). PMID- 2580923 TI - [Experimental studies on combination chemotherapy based on cell cycle analysis]. AB - Based on Peplomycin-induced cell cycle distribution analyzed by a flow-cytemetry using HeLa S-3 and SNG-M cells in vitro, we investigated reasonable periods and kinds of drug combined with pepleomycin (PEP). Changes in both the PEP treatment time and dosage produced a redistribution which decreases the number of cells in the G1 phase and increased the number of cells in the S and G2-M phases. The period with the maximum number of cells in the S phase was 12 hours in the HeLa S 3 and 16 hours in the SNG-M and, that in the G2-M phases, 16 hours in the HeLa S 3 and 22 hours in the SNG-M after the treatment. In the combination of the pep with CIS-DDP 4-hydroperoxy cyclophosphamide Adriamycin (ADR) and ACNU, the cytotoxic potency of the four drugs were CIS-DDP greater than 4-Hydroperoxy cyclophosphamide greater than ADR greater than ACNU in the HeLa S-3 and 4 Hydroperoxy cyclophosphamide greater than CIS-DDP greater than ADR greater than ACNU in the SNG-M. This suggests that the Cis and 4-Hydroperoxy cyclophosphamide were adequate for the combination with the PEP. The period of the combination should be at the time of the greatest accumulation of cells in the G2-M phase, because the pep effectively produced the G2-M partial synchronization. These results suggest that the combination chemotherapy should be based on the analysis of the cell cycle. PMID- 2580924 TI - Studies of streptococcal membrane antigen--binding cells in acute rheumatic fever. AB - Blood specimens from patients with rheumatic heart disease in both India and New Mexico were typed for the presence of B cell alloantigen 883 by use of a mouse monoclonal antibody with identical specificity to the original 883 human alloantiserum. Strong relative segregation was recorded for 883 positive B cell typing in patients with rheumatic heart disease in both geographic locations as compared with that in normal unaffected controls. In patients with acute rheumatic fever, studies of actual B-lymphocyte membrane binding by anti-883 monoclonal antibody and sonicated group A streptococcal membrane antigens showed separate but contiguous localization on isolated cell surfaces. Although physically distinct, 883 B cell alloantigen and sonicated group A streptococcal membrane antigens moved together in cell capping studies after incubation at 37 degrees C. These findings reaffirm the apparent close association between 883 B cell alloantigen and rheumatic heart disease. They also demonstrate that the B cell alloantigen 883 itself is physically distinct from but very close to sites on antigen-reactive B cells actually binding to group A streptococcal membrane antigens. PMID- 2580926 TI - Immunocytochemical localization of vasopressin-binding sites in the rat kidney. AB - The rat kidney and brain are major target organs for vasopressin (VP). A procedure was developed for immunocytochemical staining of VP and its binding sites in the kidney. This procedure involved preincubation of kidney sections with the ligand, followed by immunocytochemical detection of VP. The staining in renal tubules from Wistar rats was enhanced by preincubation of tissue sections with increasing concentrations of VP (6-6000 nmol/l). Staining was present in the epithelium of distal convolutions and collecting ducts (medullary and cortical portions) and more pronounced in the apical zone of the tubular epithelium. With high concentrations of VP in the preincubation, staining was also obtained in the thick ascending limb of the loop of Henle. There was no staining under any circumstances in proximal tubules. In the kidney of the Brattleboro rat homozygous for hypothalamic diabetes insipidus (DI) which congenitally lacks VP but responds to the peptide, exactly the same staining pattern was observed after preincubation with VP, but the maximal staining was less intense. The VP binding to the DI rat kidney, after 2 weeks treatment with VP (using Accurel implants), reached levels seen in the Wistar kidney after in-vitro preincubation with high doses of VP. PMID- 2580925 TI - Corneal organ cultures in tyrosinemia release chemotactic factors. AB - Corneal inflammation with subsequent scarring and blindness occurs in the inherited human metabolic disease tyrosinemia type II, yet putative inflammatory mediators in this disorder and in the avascular cornea in general are poorly defined. In a Tyr-fed rat model of tyrosinemia type II, intracellular crystals, presumably Tyr, are hypothesized to be responsible for the increased lysosomal activity observed in corneal epithelial lesions. Because polymorphonuclear leukocytes (PMNs) are seen only at the site of these lesions, we used this model to study humoral mediators released from Tyr-fed rat corneal organ cultures. Only Tyr-fed rats developed stromal edema and linear granular opacities in gray edematous corneal epithelium, compatible with a noninfectious keratitis. Electron micrographs confirmed epithelial edema and showed focal epithelial necrosis with PMN invasion of the stroma. Only Tyr-fed rat corneal culture supernatants contained chemotactic activity that was heat labile and moderately trypsin sensitive. Four peaks with varying amounts of chemotactic activity were found on Sephadex G-75 chromatography. Although the identity of these peaks of activity has not yet been established, we suggest that they may be responsible for the PMN infiltration observed in this model of corneal inflammation. PMID- 2580927 TI - Nuclear retinoic acid binding protein in human prostate adenomas. AB - A retinoic acid binding protein has been detected in salt extracts of nuclei obtained from human prostate adenoma. The binding was characterized by competition experiments, temperature/time studies and saturation analysis. Substantial binding was only observed after sonication of nuclei and charcoal pretreatment of a salt extract. The binding of radiolabelled all-trans-retinoic acid was displaced by all-trans-retinoic acid, retinol and to a lesser extent retinal and two synthetic retinoids, RO 10-1670 and RO 13-7410. Testosterone and dihydrotestosterone, at a 100-fold excess, had little effect on the binding. The association between retinoic acid and nuclear protein was both temperature and time dependent. At 37 degrees C, equilibrium was rapidly reached (30 min) whereas at 4 and 25 degrees C, ligand binding occurred at a slower rate. Saturation analysis performed under steady-state conditions yielded a dissociation constant of 15 +/- 2 nmol/l. Metabolism studies failed to show conversion of either radiolabelled all-trans-retinol or [3H]retinoic acid in vitro; these data suggest that both acid and alcohol forms of vitamin A are recognized by the extracted nuclear protein. The effect of three enzyme inhibitors on [3H]retinoic acid binding was studied. Binding was unaltered in the presence of aprotinin and phenylmethylsulphonyl fluoride but sodium molybdate (10 mmol/l) increased binding by 18%. The presence of a specific retinoid binding protein in prostate nuclei suggests that retinoids may play some role in the function of the gland. PMID- 2580928 TI - Transcription of similar sets of rare maternal RNAs and rare nuclear RNAs in sea urchin blastulae and adult coelomocytes. AB - We studied the sequences transcribed in the rare class of hnRNA and the rare maternal RNA set in blastula embryos and a tissue of adult sea urchins, coelomocytes. About 26% of labelled single-copy DNA formed hybrids which bound to hydroxyapatite after three cycles of hybridization with nuclear RNA from blastulae and coelomocytes. This corresponds to transcription of about 50% of the single-copy genome by both cell populations. To compare the rare hnRNA sequences synthesized by blastulae and coelomocytes directly, labelled single-copy DNA was hybridized with blastula nuclear RNA to high RNA C0t, fractionated into sequences complementary and non-complementary to blastula nuclear RNA by chromotography on hydroxyapatite, and then each fraction was rehybridized with nuclear RNA from blastulae and coelomocytes. About 62% of the labelled DNA complementary to blastula nuclear RNA and about 1.5% of the labelled DNA non-complementary to blastula nuclear RNA hybridized with nuclear RNA from both cell populations. Thus, coelomocytes and blastula embryos transcribe essentially the same single copy sequences in the rare hnRNA class. A probe for the rare maternal RNA set was isolated by hybridizing single-copy DNA with total egg RNA to high RNA C0t. 65 67% of this probe hybridized with whole-cell RNA from eggs, blastulae, plutei and coelomocytes demonstrating that essentially all rare maternal RNAs are present, and presumably transcribed, in blastulae, plutei and coelomocytes. PMID- 2580929 TI - Development in vitro of the female germ cells of the polychaete Ophryotrocha labronica. AB - In the polychaete Ophryotrocha labronica each oocyte is during its growth period associated with a single nurse cell. The fact that the oocyte-nurse cell pairs occur isolated in the female coelom makes them easily removable for analysis of their developmental ability in vitro. Using Dulbecco's modified Eagle medium supplemented with amino acids, nucleosides, foetal calf serum and sea water, we have managed to support development in vitro of germ cell pairs from early and mid-oogenesis until maturation of the oocyte, when the nurse cell degenerates and the oocyte enters meiotic metaphase. Radiolabelling of germ cells in mid oogenesis with tritiated amino acids and uridine during the first day of incubation indicates normal development with synthesis of RNA and protein, and pulses two days later verify a continued normal protein synthesis and yolk formation. The investigation confirms autosynthesis of yolk proteins in the germ cells of this species and indicates a leading role of the nurse cell in the process. PMID- 2580930 TI - Benzamide on chondrocytic differentiation in chick limb bud cell culture. AB - Benzamide, an inhibitor of (ADP-ribose) transferase, augmented chondrocytic differentiation of chick limb bud mesenchymal cells in micromass cultures; the incorporation of 35SO4(2-) into the trichloroacetic-acid-insoluble constituents of cell masses as well as the formation of cartilage nodules (Nishio, Nakanishi, Doull & Uyeki, 1983) occurred about 24 h earlier than in untreated cultures and continued to be enhanced in benzamide-treated cultures of stage 23- to 24-chick limb bud cells. Benzamide also significantly increased cell proliferation. However, benzamide did not affect DNA and RNA syntheses except for one period: 24 to 30 h after the start of culture, RNA synthesis was stimulated. From 48 h of culture, (ADP-ribose) transferase activity decreased daily in untreated cultures, whereas benzamide treatment diminished (ADP-ribose) transferase activity 24 h earlier. On the other hand, intracellular NAD levels increased daily in untreated cultures, and benzamide significantly increased the NAD levels above untreated cultures. ATP levels did not differ significantly during the culture period, and benzamide did not affect ATP levels. PMID- 2580931 TI - Synthesis of apolipoproteins, alphafoetoprotein, albumin, and transferrin by the human foetal yolk sack and other foetal organs. AB - Fragments of human foetal organs and blood at 5-11 weeks of postfertilization development were cultured in radioactive protein precursors. The secreted products were characterized by immunoprecipitation, and by measuring the mobility of the immunoprecipitates on polyacrylamide gels. It was found that secondary human yolk sacks secreted apolipoproteins A1 and B. The work of previous authors on the synthesis of other serum products by this organ and by the foetal liver and by the foetal intestines was confirmed. Within the yolk sack, the endoderm, the blood cells, and the outside epithelium reacted with antibodies against apolipoprotein A1 and transferrin. By metabolic labelling of umbilical cord blood, it was found that blood did not secrete apolipoproteins A1 and B. Blood cells could therefore not be a source of these secreted products. PMID- 2580932 TI - Growth stimulation of the immature chick oviduct by androgens: the vagina as a new target tissue. AB - Testosterone when injected alone stimulates growth of the vagina but is inactive upon the other segments of the oviduct of the immature chicken. This action of testosterone can already be detected in embryos: it is expressed by the beginning of differentiation of the vaginal mesenchyme cells into smooth muscle cells. In the treated immature chicken, stimulation of growth is considerable and is specifically caused by androgens (testosterone and 5-alpha-dihydrotestosterone); the vaginal mesenchyme differentiates into two smooth muscular layers and vaginal epithelium cells differentiate into ciliated cells and goblets cells. [3H]testosterone binding has been found in the vagina of the immature chicken (data not shown). The characteristics of testosterone binding to cytoplasmic components of the chick vagina are consistent with its identity as a testosterone receptor. PMID- 2580933 TI - TLiSA1, a human T lineage-specific activation antigen involved in the differentiation of cytotoxic T lymphocytes and anomalous killer cells from their precursors. AB - The characteristics of a novel T lineage-specific activation antigen, termed TLiSA1, are described. The antigen was detected with a mouse monoclonal antibody, LeoA1, that was raised against activated human T cells generated in mixed lymphocyte culture (MLC). The antigen became strongly expressed on T cells 48-72 h after stimulation with phytohemagglutinin, and retained expression on MLC activated T cells after 10 d of culture. The antigen was absent from a range of human T, B, myeloid, fibroblast, and tumour cell lines, but was present on the surface of the interleukin 2 (IL-2)-dependent gibbon cell line MLA-144. Analysis of the antigen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of immunoprecipitates obtained from activated human T cells demonstrated a broad band in the region of 70 kD, whereas precipitates obtained from MLA-144 revealed a single narrow band of 95 kD. The molecule was expressed with a maximum density of 66,000 copies per cell on the surface of MLC-activated T cell blasts, as assessed by Scatchard analysis. TLiSA1 was distinguished from the IL-2 receptor bound by the anti-Tac monoclonal antibody by demonstrating that the antigens did not comodulate or coprecipitate, and by constructing an IL-2-independent human T X T hybrid that expressed the TLiSA1 but not the Tac antigen. MLC with B lymphoblasts was used to generate cytotoxic T lymphocytes (CTL) specific for the stimulating cell, and anomalous killer (AK) cells able to kill melanoma target cells. The presence of LeoA1 or F(ab')2 fragments of the antibody from the beginning of coculture did not affect proliferation in these cultures, but did inhibit the induction of both CTL and AK cells from their precursors. This inhibition of differentiation by LeoA1 was confirmed under conditions of limiting dilution, where it was shown that the antibody reduced the frequency of CTL produced, and greatly (fourfold) reduced the frequency of AK cells generated from their precursors. We discuss the possibility that human CTL may express a differentiation factor receptor that is distinct from the receptor for IL-2. PMID- 2580935 TI - Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small-cell lung cancer. AB - We have found markedly deficient expression of the class I major histocompatibility antigens HLA-A,B,C and beta 2m on human small-cell lung cancer (SCLC) lines and fresh tumor samples. The deficit of HLA-A,B,C and beta 2 microglobulin (beta 2m) antigen expression was demonstrated with both radiobinding assays and indirect immunofluorescence assays. Immunoprecipitation of metabolically labeled cells with antibodies to class I antigens showed most SCLC lines to have synthesized almost no beta 2m and HLA-A,B,C proteins. Northern blot analysis, using human HLA-A,B, and beta 2m cDNA probes, showed that almost all SCLC lines tested had markedly decreased amounts of HLA and beta 2m mRNA, but both gene products could be induced with interferon treatment of SCLC lines. We conclude that human SCLC, in contrast to other lung cancer types, is characterized by greatly reduced transcription of HLA-A,B,C and beta 2m genes, which suggests the existence of a mechanism for evading the host immune response to the tumor and of an E1a-like product in this type of tumor cell. PMID- 2580934 TI - Inhibition of Epstein-Barr virus (EBV) release from the P3HR-1 Burkitt's lymphoma cell line by a monoclonal antibody against a 200,000 dalton EBV membrane antigen. AB - In raising murine hybridoma antibodies against Epstein-Barr virus (EBV)-induced membrane antigens (MA), we found one antibody that blocked the release of infectious EBV from cultured P3HR-1 cells. This monoclonal antibody (mAb) recognized a 200 kD, phosphonoacetic acid-sensitive (late) MA, and did not directly neutralize virus without complement. When this mAb was added to 33 degrees C-cultured, spontaneously EBV-producing P3HR-1 cells, the intracellular expression of viral capsid antigen and infectious virus was not inhibited, but the appearance of infectious virus in the culture medium was significantly reduced. The duration of this suppression was dependent upon the concentration of the mAb, an effect being observed to a 1:4 X 10(5) titer of the ascites mAb preparation. A more acute effect of suppression of EBV release was observed in a second model of 12-o-tetradecanoyl phorbol-13-acetate and n-butyrate induction of EBV in 37 degrees C-cultured P3HR-1 cells. Again, intracellular infectious virus production was not inhibited, but the level of infectious virus in the culture medium was significantly reduced as early as 1 and 2 d of culture with antibody. This effect was reversed within 31 h after replacement of mAb-containing medium with fresh medium. This description of antibody-mediated inhibition of EBV release might lead to the characterization of another form of immune defense for the control of EBV infections. PMID- 2580936 TI - Genetic markers of the antigen-specific T cell receptor locus. AB - The restriction enzyme Eco RI reveals DNA cleavage sites that serve to distinguish the gene locus believed to encode the beta subunit of the major histocompatibility complex (MHC)-restricted, antigen-specific receptor of the T cell in BALB/c mice from that of SJL/J mice. A monoclonal antibody, KJ16-133, also distinguishes BALB/c and SJL/J, because it recognizes an allotypic marker present on a cell-surface heterodimer believed to function as the MHC-restricted, antigen-specific T cell receptor. This study has shown that these two markers cosegregate in a set of BALB/c X SJL/J recombinant inbred (RI) mouse strains, permitting the conclusion that they are linked to within 3 centimorgans of each other, and to the kappa locus on chromosome 6. The tight linkage between these independently derived, totally different T cell markers substantially strengthens the argument that they characterize the MHC-restricted antigen-specific receptor of the effector T cell. PMID- 2580937 TI - T cell tolerance studied at the level of antigenic determinants. I. Latent reactivity to lysozyme peptides that lack suppressogenic epitopes can be revealed in lysozyme-tolerant mice. AB - Whether T cell tolerance represents direct inactivation of antigen-specific T cells via recognition of antigen plus major histocompatibility complex, or via T suppressor (Ts) cells, or a combination of these mechanisms, remains to be clarified. This problem was investigated using a novel approach based on the finding in several systems that T helper/proliferative (Th/Tp) cell-inducing antigenic determinants are dissociable from Ts cell-inducing determinants. Thus, peptide probes containing known sites that stimulate T proliferative activity, as well as peptides from distinct sites assumed to bear Ts-inducing determinants, were used in studying hen (chicken) eggwhite lysozyme (HEL)-tolerant mice. The clear prediction from clonal deletion model is that Th/Tp response potential to short peptides in the tolerant mouse would not exist, while regulatory suppression models predict the coexistence of antigen-reactive cells and antigen specific regulatory cells that prevent their expression. Adult mice, treated with 2 mg HEL in saline, were tolerant to HEL in complete Freund's adjuvant (CFA). Latent T cell proliferative responses could be revealed to determinants within two HEL peptide probes, which lacked the amino-terminal region of the molecule. This responsiveness suggested two conclusions: first, Ts cells directed against the amino terminus of lysozyme exist in the tolerant genetic responder B10.A; second, these Ts regulate the activity of functional antigen-reactive T cells directed against epitopes elsewhere on the molecule, but only in the presence of the complete molecule, HEL. Examination of neonatally induced tolerance did not reveal any latent responsiveness, supporting the hypothesis that clonal deletion or anergy is the relevant mechanism in this situation. Possible reservations in these explanations of the two tolerant states, plus analysis of the more complex "split tolerance" resulting from 20 mg HEL in saline treatment in adults, are discussed. The approach of dissociation of proliferation-inducing determinants from suppression-inducing determinants clarifies our understanding of the tolerant state and holds promise for more definitive exploration of mechanisms of T cell tolerance. PMID- 2580938 TI - Expression and T cell recognition of hybrid antigens with amino-terminal domains encoded by Qa-2 region of major histocompatibility complex and carboxyl termini of transplantation antigens. AB - Coding potential of the Q6 gene from the Qa-2a region of BALB/c Crgl mice was analyzed by a combination of hybrid class I gene construction and DNA-mediated gene transfer. Recombinant genes were created by exon shuffling of the 5' coding region of the Q6 gene and the 3' coding region of a gene encoding a transplantation antigen (Kd, Dd, or Ld), or the inverse. Some of these hybrid class I genes were expressed in the transfected mouse fibroblasts (L cells). The hybrid class I molecules encoded by the 5' end of the Q6 gene and the 3' end of the Ld gene precipitated as 45,000 mol wt molecules associated with beta 2 microglobulin. The expression of the hybrid proteins indicates that 926 basepairs of the 5' flanking region upstream of the structural Q6 gene contain a promoter that functions as a transcription initiation site in L cells. The 3' portion of the Q6 gene appears to be responsible for the lack of cell surface expression of the intact Q6 and the hybrid Ld/Q6 genes in mouse fibroblasts. Accordingly, this portion of the Q6 class I gene may play a regulatory role in tissue-specific expression. Serological analyses of hybrid Q6 proteins suggested that Q6 may be a structural gene for CR (H-2 crossreactive) antigen found normally on subpopulations of lymphocytes. If this identification is correct, Q6 gene will define a new category of class I genes encoding approximately 40,000 mol wt molecules and carrying a characteristic truncated cytoplasmic tail. Analysis of L cells transfected with Q6 hybrid genes demonstrated also that the cytotoxic T cells specific for Qa-2a region-coded antigens recognize the amino-terminal alpha 1-alpha 2 domain of Q6 fusion products. This recognition can be blocked by anti Qa-2a alloantiserum and monoclonal antibodies reactive with the alpha 3-beta 2 microglobulin portion of the Q6 hybrids. We propose that the structural requirements for the anti-Qa-2a cytotoxic T lymphocyte-specific epitopes on target molecules are the same as for anti-H-2-alloreactive cytotoxic T lymphocyte determinants on transplantation antigens and that the mechanism of target recognition is similar in both cases. This interpretation is consistent with the following structural similarities found in both categories of class I molecules: (a) Kd and Q6 alpha 1-alpha 2 domains share serologically defined epitopes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2580941 TI - Context effects in symbolic magnitude comparisons. AB - Five experiments demonstrate that context has an effect on the ease with which people can determine the relative sizes of pairs of large and small animals. In a standard context, people are faster at choosing the larger of two large animals and the smaller of two small animals. However, when only pairs of small animals are presented (Experiment 1), relatively large pairs (RABBIT-BEAVER) are treated as if they were large animals and are discriminated more rapidly under the choose larger instruction. Similarly, when only large animals are presented (Experiment 2), the smaller of these are now treated as if they were small animals. Several models are presented that account for these effects of context, and these models are examined in subsequent experiments that impose yet other variations in magnitude pairings. The results demonstrate the importance of context in comparative judgement and place important constraints on theories of linear orders. PMID- 2580939 TI - Obligatory role of gamma interferon in T cell-replacing factor-dependent, antigen specific murine B cell responses. AB - The role of gamma interferon (IFN-gamma) in T cell-replacing factor (TRF) activity for antigen-specific plaque-forming cell (PFC) responses in vitro was studied using antibodies to murine IFN-gamma (Mu IFN-gamma). TRF activity was present in supernatants (Sn) of Con A- or mixed leukocyte reaction-stimulated murine spleen cells as well as in an IL-2-rich fraction of phytohemagglutinin stimulated human peripheral blood lymphocyte Sn and in the Sn of the Gibbon T lymphoma MLA-144. The human TRF was highly active with cells from nu/nu mice and normal mice but not with cells from animals with the xid immunologic defect, similar to the activity of murine TRF. Antibodies to IFN-gamma consisted of hyper immune rabbit antisera, IFN-gamma affinity-purified rabbit immunoglobulin and an interspecies hybridoma specific for Mu IFN-gamma. The results show that the activities of all preparations of TRF are markedly diminished or abrogated by antibody to Mu IFN-gamma but not by antibodies to human IFN-gamma (Hu IFN-gamma), nor by normal rabbit sera or purified rabbit Ig. The degree of inhibition was dose dependent and was quantitatively reversed by the addition to the cultures of recombinant-derived Mu IFN-gamma (Mu rIFN-gamma) but not Hu rIFN-gamma. This reversal was fully antigen specific and thus not attributable to polyclonal B cell activation by IFN-gamma, which is inactive alone in the TRF assay. Kinetic analysis shows that IFN-gamma must act by 24-48 h to produce PFC responses at 4 d. Together, the data demonstrate that IFN-gamma is a necessary mediator for TRF effects and that IFN-gamma is induced by TRF from T-depleted murine spleen cells in sufficient quantity to support large antibody responses. The source of this IFN-gamma may be the potent natural killer cells that are induced in cultures stimulated with TRF. PMID- 2580940 TI - [Quantitative determination of protein in the urine by a sensitive nephelometric method]. AB - The nephelometric method of Reiber ((1980) J. Clin. Chem. Clin. Biochem. 18, 123 127) for quantitation of proteins in cerebrospinal fluid was modified for urine. Protein concentrations between 50 and 500 mg/l (method A) or between 5 and 70 mg/l (method B) can be measured. Values greater than 150 mg/l correlate well with the Biuret- and the Coomassie method (r = 0.9804 and r = 0.9925, respectively). For lower concentrations, only albumin, determined by an enzyme-immuno-assay, gave a good correlation (r = 0.9342). The following pharmaceuticals did not influence the results: penicillin, gentamycin sulphate, dihydralazine sulphate, amoxicillin and furosemide. A reference range of 7-56 mg/24 h was established (n = 52, 90% confidence interval). PMID- 2580942 TI - Nucleic acid studies on halophilic archaebacteria. AB - DNA-16S rRNA hybridization studies of archaebacterial halophiles revealed nine major groups. High (greater than 45%) DNA-DNA homologies were found only within DNA-rRNA groups. The DNA-DNA homology between the type strains of Halobacterium halobium, Hb. salinarium and Hb. cutirubrum was greater than 70%. The implications for the taxonomy of the extreme halophiles are discussed. PMID- 2580943 TI - Interactions between mutations affecting ribosome synthesis in Escherichia coli. AB - RNA synthesis was followed during amino acid starvation of strains of Escherichia coli that contained both the relaxed (relA) mutation and a mutation affecting ribosome assembly that results in oversynthesis of RNA. The ribosome mutation did not by itself lead to relaxedness. The relaxed mutation could be expressed in organisms that contained the ribosome mutation. PMID- 2580944 TI - Capsaicin and regulation of respiration: interaction with central substance P mechanisms. AB - The neuropharmacological effects of capsaicin (CAPS) (8-methyl-N-vanillyl-6 nonenamide) have been closely linked to the peptide neurotransmitter substance P (SP). In order to elucidate SP mechanisms in peripheral and central control of breathing we have studied the respiratory effects of CAPS and SP administration to neonatal and adult rats using a whole body plethysmographic method. CAPS (3 and 30 micrograms) induced an immediate apnea after intravenous injection. This effect could be reduced by vagotomy but not further changed by combined vagotomy and glossopharyngectomy. The apnoic periods were followed by periods of tachypnea. Intracerebroventricular (i.c.v.) administration of CAPS resulted in an increased tidal volume (VT) and a decreased respiratory frequency (f), i.e. a respiratory response similar to that seen after i.c.v. SP. No apnoic episodes were seen after i.c.v. injection. The respiratory pattern after acute i.c.v. CAPS administration was not significantly changed by neonatal CAPS pretreatment. However, while saline pretreated control animals responded to an i.c.v. injection of SP with an increase in VT and inspiratory drive (VT/TI), animals pretreated with CAPS responded with a shortening of inspiratory and expiratory time in combination with an increase in VT. Similar changes have been observed in vagotomized animals after SP administration. It is concluded that CAPS elicits apnea via mechanisms located outside the CNS, which cannot be fully deafferented by combined vagotomy and glossopharyngectomy. Furthermore, CAPS i.c.v. induces a stimulation of respiration by a central mechanism of action, possibly due to a release of SP. Neonatal pretreatment with CAPS modifies the respiratory response to i.c.v. SP. This effect might be due to an impairment in tonical afferent SP mechanisms to the central respiratory regulating system and possibly also to an impairment of central SP mechanisms involved in respiration. PMID- 2580945 TI - Selective inhibition of MAO-A but not MAO-B activity increases rat pineal melatonin. AB - Clorgyline, a selective MAO-A inhibitor, increased (5 times) rat pineal melatonin and N-acetyl-serotonin (NAS) content, and decreased 5-HIAA level by 80%. Deprenyl, a selective MAO-B inhibitor, did not change melatonin or other pineal indoles content. The data obtained show that inhibition of MAO-A but not B enzyme is responsible for pineal melatonin increase caused by MAO inhibitors. It is suggested that the stimulation of melatonin synthesis caused by MAO inhibitors may contribute to their antidepressive effect. PMID- 2580946 TI - Membrane mechanism of neuroendocrine caudo-dorsal cell inhibition by the ring neuron in the pond snail Lymnaea stagnalis. AB - Ovulation in the pond snail Lymnaea stagnalis is controlled by the neuroendocrine caudo-dorsal cells (CDCs) in the cerebral ganglia, which release an ovulation hormone during a period of impulse activity. Firing of the single RN in the right cerebral ganglion hyperpolarizes the CDCs. This hyperpolarization is caused by the opening of potassium channels in the axons that connect both the CDC clusters. By this action, that presumably is mediated by axonal branches of the RN in the intercerebral commissure closely associated with these CDC axons, the RN decouples both the CDC clusters. Although the RN has negative feedback on the CDC, it does not control afterdischarge characteristics. The authors suggest that the RN, next to the egg-laying behavior, is involved in another behavior, not compatible with ovulation. Male reproductive activity is presented as a possible candidate for such behavior. PMID- 2580947 TI - Regulation of calcium influx into buccal muscles of Aplysia by acetylcholine and serotonin. AB - Acetylcholine (ACh) causes contraction of Aplysia buccal muscles E1 and I5, and serotonin (5-hydroxytryptamine, 5-HT) enhances ACh-elicited contractions of these muscles. Possible roles of calcium influx in mediating these responses were examined by studying influx of 45Ca++. 5-HT increased calcium influx into both I5 and E1. Maximal influx occurred at 10(-6) M 5-HT and the increased influx could be sustained in the presence of 5-HT for at least 10 min. ACh also caused calcium influx, and calcium influx increased approximately in proportion to log[ACh] from 10(-5) M to 10(-3) M ACh. 5-HT and ACh probably bring about calcium influx by different mechanisms since the effect of ACh was additive to a maximal 5-HT response, and 10(-4) M hexamethonium bromide inhibited the increased influx caused by ACh but did not affect influx caused by 5-HT. Cyclic AMP analogues and forskolin neither caused an increase in calcium influx nor an increase in the influx caused by ACh. The data support a model in which ACh-elicited contractions of I5 and E1 are due primarily to calcium entry across the extracellular membrane, and 5-HT can "load" an intracellular site by a mechanism different from that activated by ACh. The data do not support a role for cyclic AMP in mediating the calcium influx response to 5-HT. PMID- 2580949 TI - "Peripheral-type" binding sites for benzodiazepines in brain: relationship to the convulsant actions of Ro 5-4864. AB - Previous studies have shown that Ro 5-4864 is a potent convulsant and increases the firing rate of substantia nigra zona reticulata neurons. The pharmacologic profile of compounds that antagonize these actions suggested that the effects of Ro 5-4864 were not mediated by "brain-type" benzodiazepine receptors. We examined a number of compounds that are structurally related to Ro 5-4864 for their capacities to displace [3H]Ro 5-4864 from "peripheral-type" binding sites and their potencies as convulsants (or as antagonists of Ro 5-4864-induced convulsions). It was observed that compounds such as KW 3600 (the N-desmethyl analog of Ro 5-4864), which have very low affinities for "peripheral-type" sites, are convulsants with a potency nearly equal to that of Ro 5-4864. In contrast, compounds such as Ro 5-6900 and PK 11195, which bind with very high affinities to "peripheral-type" binding sites, are neither convulsants nor do they antagonize the convulsant actions of Ro 5-4864. Within a series of compounds that are structurally related to Ro 5-4864 there is a good correlation (r = 0.93; p less than 0.01) between their potencies as convulsants and their capacities to displace [35S]t-butylbicyclophosphorothionate from sites that may be associated with the chloride ionophore. Thus, it appears that occupation of "peripheral type" binding sites by high-affinity ligands may not be directly involved in the convulsant actions of Ro 5-4864 and related compounds. PMID- 2580948 TI - Substance P in human plasma is degraded by dipeptidyl peptidase IV, not by cholinesterase. AB - Human serum cleaves two dipeptides from the N-terminus of the neurohormone substance P. It has been suggested that this degrading activity is inherent to serum cholinesterase. We oppose this, because it turned out that highly purified serum cholinesterase contains traces of dipeptidyl peptidase IV, an enzyme known to attack the N-terminus of substance P. The peptidase is incompletely separated from cholinesterase during the procainamide-gel affinity chromatography as the last step of the usual purification procedure. Physostigmine completely inhibits the hydrolysis of butyrylthiocholine by such purified cholinesterase preparations, but not their substance P-degrading activity. Vice versa, epsilon carbobenzoxy-lysylproline, an inhibitor of dipeptidyl peptidase IV, inhibits the peptidase activity of these preparations more than their esterase activity. After rechromatography on procainamide gel the peptidase is completely separated and the remaining cholinesterase has lost its substance P-degrading activity. We conclude that the N-terminal region of substance P is not degraded by cholinesterase but by the contaminating dipeptidyl peptidase IV, a different serine enzyme. PMID- 2580950 TI - Neurochemical profile of Lu 19-005, a potent inhibitor of uptake of dopamine, noradrenaline, and serotonin. AB - The neurochemical profile of a new compound, Lu 19-005 [(+/-)trans-3-(3,4 dichlorophenyl)-N-methyl-1-indanamine hydrochloride], has been investigated. Lu 19-005 is a potent inhibitor of the synaptosomal uptake of 3,4 dihydroxyphenylethylamine (dopamine, DA), noradrenaline (NA), and 5 hydroxytryptamine (5-HT, serotonin). In this respect it resembles diclofensine, whereas compounds such as GBR 13.069 and bupropion are more selective DA-uptake inhibitors. Although Lu 19-005 releases DA in in higher concentrations it must be considered as an uptake inhibitor, as the accumulation of DA is inhibited in much lower concentrations. Lu 19-005 attenuates the DA and NA depletion caused by 6 hydroxydopamine in mouse brain. These properties confirm the DA- and NA-uptake inhibitory properties of the compound. In receptor-binding models and functional in vitro tests Lu 19-005 is devoid of dopaminergic-, serotonergic-, noradrenergic , histaminergic-, and cholinergic-inhibiting properties. Since DA, NA, and 5-HT seem to be involved in depression, the profile of Lu 19-005--with equally potent activity on the three neuronal systems--makes it an interesting experimental tool and a potential new antidepressant agent. PMID- 2580951 TI - Dopamine inhibits forskolin- and 3-isobutyl-1-methylxanthine-induced dark adaptive retinomotor movements in isolated teleost retinas. AB - We have been investigating the mechanisms of diurnal and circadian regulation of teleost retinomotor movements. In the retinas of lower vertebrates, photoreceptors and melanin pigment granules of the retinal pigment epithelium (RPE) undergo movements at dawn and dusk. These movements continue to occur at subjective dawn and dusk in animals maintained in constant darkness. Cone myoids contract at dawn and elongate at dusk; RPE pigment disperses into the epithelial cells' long apical processes at dawn and aggregates into the cell bodies at dusk. We report here that forskolin, an adenylate cyclase activator, and 3-isobutyl-1 methylxanthine (IBMX), a phosphodiesterase inhibitor, each induces dark-adaptive cone and RPE retinomotor movements in isolated light-adapted green sunfish retinas cultured in constant light. Forskolin induces a 22-fold elevation in retinal cyclic AMP content. Forskolin- and IBMX-induced movements are inhibited approximately 65% and 95%, respectively, by 3,4-dihydroxyphenylethylamine (dopamine). However, dopamine does not inhibit dark-adaptive movements induced by dibutyryl cyclic AMP. Epinephrine is much less effective than dopamine in inhibiting forskolin-induced movements, while phenylephrine and clonidine are totally ineffective. These results are consistent with our previous findings that treatments that increase intracellular cyclic AMP content promote dark-adaptive retinomotor movement. They further suggest that dopamine inhibits adenylate cyclase activity in photoreceptors and RPE cells and thereby favors light adaptive retinomotor movements. PMID- 2580952 TI - Uptake and anterograde axonal transport of Aleuria lectin in retinal ganglion cells of the rabbit. AB - A fucose-specific lectin from Aleuria aurantia was used to study the dynamics of neuronal membrane glycoproteins. Albino rabbits received vitreal injections of affinity-purified 125I-Aleuria lectin. The radioactive probe was internalized by adsorptive endocytosis into retinal ganglion cells, and transported intact down to the nerve terminals in the contralateral geniculate bodies and superior colliculi. We found that the radiolabeled lectin was transported with at least two distinct rates (I, approximately 205 mm/day; II, approximately 45 mm/day) corresponding to the two rapid phases of anterograde transport of endogenous polypeptides described earlier in this system. This is the first evidence that an exogenous macromolecule may be transported along the axon at more than one velocity. PMID- 2580953 TI - Expression of hyaluronectin by C-6 glial cells at high density. AB - Hyaluronectin, a brain glycoprotein that has been localized to the nodes of Ranvier in vivo and to oligodendrocytes in primary cultures of neonatal rat brain cells, was shown by using an unlabeled immunoperoxidase method to be present in C 6 glial cells grown to high density. The density-dependent expression of this glycoprotein is in accordance with the known properties of the glial stem cells, i.e., induction of differentiated properties such as 2',3'-cyclic nucleotide-3' phosphohydrolase, glutamine synthetase, S-100 protein, and glial fibrillary acidic protein. PMID- 2580954 TI - Axonal transport of polyamines in intact and regenerating axons of the rat sciatic nerve. AB - The axonal transport of putrescine or its polyamine derivatives spermidine or spermine is a subject of some debate. We investigated this question by injecting [3H]putrescine into the lumbar spinal cord of the rat and measuring the accumulation of radioactivity central to ligatures placed on intact and regenerating sciatic nerves. In normal nerves, approximately twice as much radioactivity built up proximal to these ligatures 2 or 3 days after injection than at more distal ligatures used to control for accumulation of radioactivity which might be due to tissue damage alone. In regenerating nerves the amount of radioactivity accumulating at the ligature was approximately five times that at the distal ligature and two to three times greater than in intact nerves. The identity of the radioactivity in regenerating nerves, determined on an amino acid analyzer, was found to be primarily spermidine and an unknown compound that migrated as a frontal elution peak. Autoradiographic analysis showed that the radioactivity was largely confined to axons, but a significant amount of the silver grains was associated with Schwann cells and myelin sheaths surrounding labeled axons in both intact and regenerating nerves. The data indicate that polyamine derivatives of putrescine are transported axonally in rat sciatic nerves, and some of this transported material accumulates in Schwann cells surrounding the labeled axons. These processes are apparently augmented during regeneration of the injured axons. PMID- 2580955 TI - Possible allosteric interaction of 4-aminopyridine with rat brain muscarinic acetylcholine receptors. AB - The interaction of the potassium channel blocker 4-aminopyridine (4-AP) and its analogs with muscarinic acetylcholine receptors was studied in rat brain homogenate. 4-AP displaced specific [3H]quinuclidinyl benzilate [( 3H]QNB) binding in a concentration-dependent fashion. Hill coefficient values decreased with increasing the concentration of [3H]QNB and different analogs of 4-AP demonstrated varying potencies. Scatchard analysis of saturation isotherms of specific [3H]QNB binding showed that low concentrations of 4-AP slightly reduced maximum binding without affecting the equilibrium dissociation constant, whereas higher concentrations reduced maximum binding further and significantly increased the equilibrium dissociation constant. Schild plots of these data resulted in curvilinear functions. The results are discussed in terms of possible allosteric interactions between potassium channels and muscarinic receptor binding sites. PMID- 2580956 TI - [3H]Nitrendipine binding to calcium channels in bovine and rat pituitary. AB - [3H]Nitrendipine was used to label sites in homogenates of bovine anterior and neurointermediate lobes of the pituitary gland. The amount of specific binding in the anterior lobe was 1.82 +/- 0.30 pmol/g wet weight of tissue and the KD was 1.44 +/- 0.02 X 10(-10) M. Preliminary experiments indicated a similar amount of binding in bovine neurointermediate lobe. In competition studies nimodipine and nisoldipine (two potent voltage-sensitive calcium channel blockers) displayed IC50 values of 1.6 and 6.8 X 10(-10) M, respectively. Verapamil and the verapamil like calcium channel blockers D-600 and tiapamil competed in a complex manner for the [3H]nitrendipine specific binding to bovine anterior pituitary homogenates. Autoradiographical studies demonstrated specific [3H]nitrendipine binding sites distributed approximately equally in the anterior and posterior lobes, but not in the intermediate lobe of the rat pituitary. In general the properties of [3H]nitrendipine binding in the pituitary tissue resemble strongly the properties of [3H]nitrendipine binding in the brain which is believed to be to voltage sensitive calcium channels. These results provide support for the hypothesis that calcium channels are involved in pituitary hormone secretion and that drugs that interact with calcium channels may modulate the secretory process directly at the level of the pituitary. PMID- 2580957 TI - Reinduction of experimental allergic encephalomyelitis in convalescent Lewis rats with cyclophosphamide. AB - Experimental allergic encephalomyelitis (EAE) in Lewis rats is an acute, monophasic autoimmune disease, and rats recovering from EAE are generally resistant to active reinduction. However, following immunosuppression with a high dose (100-200 mg/kg) of cyclophosphamide (CY), EAE was reinduced in convalescent rats, irrespective of whether or not they were rechallenged with the encephalitogenic inoculum. Reinduction of EAE was not observed in rats treated with low doses (20 mg/kg or less) of CY. A selective inhibition of suppressor cells during the convalescent stage may be responsible for the reinduction of EAE in Lewis rats. PMID- 2580958 TI - Site-specific antibodies to rat myelin proteolipids directed against the C terminal hexapeptide. AB - A site-specific antiserum against the rat myelin proteolipids was produced in rabbits by injection of a synthetic polypeptide composed of the C-terminal amino acids of the proteolipid sequence. The immunogenic hexapeptide H-Gly-Arg-Gly-Thr Lys-Phe-OH was coupled to chicken egg-albumin with dimethylsuberimidate. Antibodies specific for this peptide reacted with the 2 myelin proteolipid protein bands after SDS polyacrylamide gel electrophoresis and electrophoretic transfer onto nitrocellulose. Immunocytochemical investigations with this anti peptide antiserum showed that the Golgi complexes of the oligodendrocytes were highly labeled as noted previously with multivalent antibodies. Labeling of vesicles and discontinuous staining of the plasmalemma were also observed in the most actively myelinating oligodendrocytes. In contrast to previous results, the major dense line was free of staining; this may indicate that at this site the C terminal hexapeptide is inaccessible to these antibodies and perhaps buried in the lipid bilayer, in disagreement with the proposed organization of the myelin proteolipid in the myelin membrane. PMID- 2580959 TI - Antigenic heterogeneity of human anaplastic gliomas and glioma-derived cell lines defined by monoclonal antibodies. AB - The antigenic heterogeneity of human neuroectodermal tumors defined by both murine and human monoclonal antibodies (MAs) is reported; no patterns of reactivity defining degree of anaplasia, in vitro morphology, or immunogen used were apparent. We investigated the reactivity of 20 distinct murine MAs defining markers of glioma-associated or predominantly lymphoid distribution for 13 human glioma-derived (HGL) cell lines and frozen sections of 19 human glioblastoma multiforme (GBM) and six astrocytomas (AST). Methods included radioimmunoassay, immunofluorescence, immunohistochemistry, and absorption analysis. Two markers, HLA-A,B and human Thy-1, exhibited no deviation; all HGL cell lines tested bound high levels of specific MA. Individual HGL cell line reactivity with the MA panel ranged from 30 to 70%. HGL cell lines (7/13) which reacted with greater than or equal to 50% of the antiglioma MAs had the highest (30-70%) positive reactivity rates with the anti-lymphoid marker MA panel; complex antigenicity in one system correlated with multiple antigens in the other. Within the anti-lymphoid marker MA panel, subpopulations of 4/13 HGL cell lines were clearly positive for the HLA DR (Ia) antigens; another 3/13 HGL cell lines were strongly positive for common acute lymphocytic leukemia antigen (CALLA). With the exception of Thymocyte 1 antigen (Thy-1), reactivity for early and mature T-cell markers was infrequent and sporadic. Lymphoid marker expression by HGL cell lines is highly heterogeneous, ranging from few (Thy-1 and HLA-A,B) to complex expression of Ia, T-cell, and lymphoid tumor markers. GBM and AST tissues were antigenically less complex; for each of 6/8 anti-glioma MA, 70-100% of GBM and 66-100% of AST were positive. Two MAs were highly reactive (7/10, 8/9) with GBM sections and minimally so (1/6) with AST. Antigenic expression in gliomas is complex and heterogeneous; however, clear differences in lymphoid marker expression, the identification of widely and rarely expressed glioma-associated antigens, and the potential of immunologic differentiation between GBM and AST by large panels of MAs will serve to reduce the complexity and may be of potential diagnostic or prognostic significance. PMID- 2580960 TI - The role of cerebral blood volume changes in brain specific-gravity measurements. AB - Cerebral blood volume (CBV) was calculated in gerbils from specific-gravity (SG) changes between normal and saline-perfused brains. Furthermore, changes in CBV were investigated during ischemia using carbon-14-labeled dextran (MW 70,000) as an intravascular marker. Both data were used to evaluate the possible error due to a change in CBV on the measurement of ischemic brain edema by the SG method. The methodological error found was 0.0004 for a 100% CBV change. This error is insignificant, being less than the standard deviation in the SG measured for the gerbil cortex (SG 1.0494 +/- 0.0006). Thus, CBV changes are not responsible for the SG variations observed during the first phase of ischemia. These variations are better explained as an increase of brain water content during ischemia. PMID- 2580961 TI - Monoclonal antibodies in nuclear medicine. AB - Monoclonal antibodies have been a part of biomedical research for nearly a decade, yet a comparable period of time may be required before radiolabeled monoclonal antibodies come into standard practice in the diagnosis and therapy of human disease. Difficulties in identifying appropriate antigens, developing the optimal antibody species, attaching the most effective radiolabel and choosing the best method of administration all confound present investigations. The problems confronting therapeutic applications are, for the most part, an extension of those associated with diagnostic techniques. Still, there is much well-deserved optimism, and progress in all areas of investigation will ultimately come together to resolve most if not all of these problems. It is inevitable that monoclonal antibodies will have significant impact on the practice of nuclear medicine, and presented here is a review of the basic knowledge as well as an update on the current status of radiolabeled monoclonal antibodies in medicine. PMID- 2580962 TI - Serial alterations in the forms of immunoreactive pancreatic cationic trypsin in plasma from patients with acute pancreatitis. AB - We employed a radioimmunoassay for human cationic trypsin to define the time course for alterations in the molecular forms of this enzyme in plasma from patients with pancreatitis. Six patients developed acute pancreatitis as a complication of a known disorder [three, Reye's syndrome; two, hemolytic uremic syndrome (HUS); one, choledochal cyst]. The immunoreactive forms of cationic trypsin were determined by gel filtration of each plasma sample followed by radioimmunoassay of the column fractions. Early in the course of the disease, predominantly free trypsinogen was released into the circulation in five patients. In the three patients with Reye's syndrome, subsequent plasma samples showed, in addition to free trypsinogen, increasing amounts of immunoreactive trypsin complexed to alpha 2-macroglobulin and alpha 1-protease inhibitor. In contrast, subsequent samples from the two patients with HUS contained little or no inhibitor-bound trypsin. The remaining patient had intermediate concentrations of cationic trypsin complexed to these two circulating protease inhibitors. Five patients died and postmortem studies showed a striking correlation between the histological severity of acute pancreatic inflammation and the amount of immunoreactive trypsin complexed to alpha 2-macroglobulin and alpha 1-protease inhibitor. This preliminary study suggests that measurement of alpha 2 macroglobulin or alpha 1-protease inhibitor-bound trypsin may be a useful method of monitoring the progression and severity of disease in patients with acute pancreatitis. Characterization of serial changes in the forms of circulating pancreatic proteases may enhance our understanding of time-dependent pathophysiologic events, possibly leading to improved forms of specific therapy. PMID- 2580963 TI - The effect of dietary protein quality and feeding level on milk secretion and mammary protein synthesis in the rat. AB - Protein synthesis was studied in mammary tissue of rats fed diets deficient in protein quality and/or restricted in food intake throughout gestation and lactation. Diets containing 25% wheat gluten (WG), wheat gluten plus lysine and threonine (WGLT), or casein (C) were pair-fed from conception until day 15 of lactation at 100% or 85% of WG ad libitum consumption (PF100 and PF85, respectively). A seventh group was fed C ad libitum. Rates of protein synthesis were measured in vivo at day 15 of lactation from incorporation of [3 3H]phenylalanine. At both PF100 and PF85, fractional and absolute rates of mammary gland protein synthesis were two- to three-fold higher in rats fed C than in those fed WG. Pup weights showed similar treatment effects. Both mammary protein synthesis rates and pup weights were significantly higher in rats fed C at PF85 than rats fed WG ad libitum. Food restriction from PF100 to PF85 depressed pup weights and mammary protein synthesis rates in rats fed WGLT, but had no effect in rats fed WG. These results demonstrate that when food intake is restricted, improvement of protein quality of the maternal diet increases milk output in the rat in association with increased rates of mammary protein synthesis. PMID- 2580964 TI - Reducing medical fears in a general population of children: a comparison of three audiovisual modeling procedures. PMID- 2580966 TI - Rorschach content interpretation in post-traumatic stress disorders: a reply to Carr. AB - In traumatized patients, Rorschach responses draw from a variety of sources, including the traumatic event itself, past and current experiences, and internal fantasy. As complex and highly condensed mental constructions, these responses often serve to reveal the meaning of the trauma in terms of the patient's prevailing personality conflicts. In many cases, this meaning may be hidden in the response's distortion of or elaboration on images drawn from the actual event. PMID- 2580965 TI - Carrageenan-induced inflammation and its effects on mitotic activity and keratinization of gingival epithelium. A histologic and autoradiographic study. AB - This study was undertaken in order to: evaluate the cell population in carrageenan-induced inflammation and investigate the extent to which this inflammation modified mitotic activity, and keratinization of the sulcular epithelium induced by daily prophylaxes in monkeys. Normal-keratinized oral gingival epithelium was also evaluated for these processes in the same gingival specimens. Each of three adult Rhesus monkeys received a thorough prophylaxis 1 week prior to the experiment. Over the 10-week experimental period, each monkey received daily rubber cup prophylaxes. In addition, during the last 10 days, daily gingival injections of a 1% carrageenan saline solution and normal saline solution were given. One hour prior to sacrifice, each monkey received an intravenous injection of tritiated thymidine, 1 microCi/gram of body weight. After sacrifice and tissue processing, the histologic sections were evaluated. It was found that the carrageenan solution injected into gingival tissues produced an acute inflammatory response consisting of polymorphonuclear leukocytes PMNs (61.3%), lymphocytes (5.2%), monocytes/macrophages (23.5%), plasma cells (2.0%) and unidentified cells (3.8%). An Inflammatory Index and a Mitotic Activity Index were determined, and keratin length and widths were measured. Data were analyzed statistically using analysis of variance. Pairwise comparisons were also made using Scheffe's method of multiple comparisons. The study showed that: carrageenan solutions injected into gingival tissues elicited an acute inflammation; acute inflammation present in gingival connective tissue stimulated an increase in mitotic activity in subjacent gingival epithelium; acute inflammation within gingival tissues did not modify the induced-keratinized sulcular epithelium, or the normally-keratinized oral gingival epithelium; and acute inflammation may not necessarily affect tissue keratinization, if bacterial plaque is removed daily. PMID- 2580967 TI - Effects of sodium substitutes on transient inward current and tension in guinea pig and ferret papillary muscle. AB - We used ouabain-treated guinea-pig and ferret papillary muscles to study transient inward current (Iti), after-contractions, and tonic tension development during voltage-clamp pulses. Li, sucrose and choline were used isosmotically as Na substitutes to evaluate the effect of altering the Na equilibrium potential. We were unable to detect outward Iti at any potential up to +30 mV in normal or Na-depleted solutions. However, reduction of Na had a biphasic effect on Iti, initially increasing it and then reducing it at all clamp potentials from -50 to +20 mV. After-contractions were also initially increased and, in sufficiently Na depleted solutions, decreased by reduction of extracellular Na. However, the peak in the after-contraction always occurred later than the increase in Iti and frequently coincided with the maximum suppression of the current. Complete suppression of after-contractions was not often achieved and always required more complete Na replacement than Iti suppression. Tonic tension responses were reduced by Na replacement, usually in synchrony with the reduction of Iti. The responses of Iti to Na replacement are consistent with a model of electrogenic Na Ca exchange over the potential range positive to -50 mV. The responses deviate from the predictions of the model at more negative potentials. The results are consistent with the previous proposal that oscillatory changes in internal free Ca concentration underlie both Iti and after-contractions. PMID- 2580968 TI - Lateral filamentary spacing in chemically skinned murine muscles during contraction. AB - A mouse toe muscle was chemically skinned with saponin and the 1,0 spacing of the hexagonal myofilament lattice at a sarcomere length of 2.5 micron was measured with the X-ray-diffraction method. In the relaxed state, the 1,0 spacing was 40.8 nm. When the muscle was maximally activated at pCa 4.4, the spacing decreased to 38.4 nm. During contractions at lower calcium concentrations, the spacing decreased less. In rigor, the spacing decreased to almost the same extent as during maximum contraction, although the rigor tension was only 8% of the maximum tension. When the spacing in relaxed muscle had been adjusted osmotically to about 38 nm, activation caused no further decrease in the spacing. The results support the view that the force responsible for the lattice shrinkage during contraction is produced by cross-bridges displaced from their optimum lateral positions. PMID- 2580969 TI - Relation of sodium pump inhibition to positive inotropy at low concentrations of ouabain in rat heart muscle. AB - Low concentrations of ouabain which produce a positive inotropic effect on rat ventricular muscle do not inhibit the isolated Na+-K+-ATPase enzyme from this tissue, suggesting that these low-concentration inotropic effects are not related to sodium pump inhibition (Erdmann, Philipp & Scholz, 1980; Adams, Schwartz, Grupp, Grupp, Lee, Wallick, Powell, Twist & Gathiram, 1982). We tested this hypothesis by continuously measuring intracellular Na+ activity with Na+ selective micro-electrodes and, separately, twitch tension of rat ventricular muscle during exposure to and wash-out of ouabain. Intracellular Na+ activity (aiNa) and transmembrane potential of quiescent muscle cells averaged 8.5 +/- 2.6 mM (mean +/- S.D., n = 27) and -79.2 +/- 2.4 mV (n = 34) respectively. Low concentrations of ouabain (0.1, 0.5 and 1.0 microM) produced concentration dependent increases in both aiNa and twitch tension. At lower concentrations of ouabain (0.01 and 0.05 microM), no detectable changes in aiNa and twitch tension were observed. The data strongly indicate that in rat ventricular muscle sodium pump inhibition is present at low concentrations of ouabain which produce positive inotropy. This is consistent with previous results in canine and sheep cardiac Purkinje fibres. PMID- 2580970 TI - Transport of sodium and chloride across rat gastric mucosa in vitro. AB - The effects of ion substitution, inhibitors and variations in transmural p.d. on the movements of sodium and chloride across an in vitro preparation of rat gastric mucosa have been studied. The tissue maintained net steady-state transport of sodium in the mucosal-to-serosal direction in the absence of transmural gradients of electrochemical potential. Sodium transport was independent of the presence of chloride, and was abolished by 1 X 10(-5) M amiloride. The inhibitor produced a decrease in short-circuit current equivalent to the depression of sodium transport, indicating that the sodium transport process was electrogenic. Variations in transmural p.d. showed that the sodium transport process included two components: one that varied with p.d. and one that was independent of it. These findings have been interpreted in terms of a system for sodium transport composed of three components: two rate-limiting entry mechanisms at the apical membrane, one of which can be represented as a conductive channel for sodium diffusion and the other as a neutral process possibly a sodium-hydrogen exchanger, and a voltage-independent pump at the basolateral membrane analogous to the constant-current pump models described in some other epithelia. The tissue maintained a net secretory movement of chloride in the short-circuited condition. The process responsible for net transport of chloride could be resolved into two components: one that was sodium dependent, electrogenic, and abolished by 8 X 10(-3) M-acetazolamide, and one that was independent of the presence of sodium, electrically silent and abolished by 5 X 10(-4) M-SITS (4-acetamido-4'-isothiocyano-2,2'-disulphonic acid stilbene). Both components of the chloride transport process varied with p.d. These findings were interpreted in terms of a system of three components: two entry mechanisms at the basolateral membrane including a coupled sodium-chloride influx process and a chloride-bicarbonate exchanger in parallel, and a rate-limiting conductive channel at the apical membrane. In addition, the studies on the effects of variations in transmural p.d. on chloride fluxes revealed a symmetrical voltage independent component, dependent on the presence of chloride in the trans compartment, and it was suggested that this component may reflect the presence of a chloride-chloride exchange mechanism. PMID- 2580971 TI - gamma-Aminobutyric-acid- and pentobarbitone-gated chloride currents in internally perfused frog sensory neurones. AB - gamma-Aminobutyric-acid- (GABA) and pentobarbitone-induced Cl- currents (ICl) were studied in isolated frog sensory neurones after suppression of Na+, K+ and Ca2+ currents using a suction-pipette technique combining internal perfusion with voltage clamp. All GABA-sensitive neurones responded to pentobarbitone. Both GABA and pentobarbitone-induced ICl reversed at the Cl- equilibrium potential (ECl). The dose-response curve for maxima of GABA-induced ICl was sigmoidal with a mean concentration producing a half-maximum response, Ka of 2 X 10(-5) M at a Hill coefficient of 1.8. In the presence of pentobarbitone, the GABA dose-response curve shifted to the left without affecting the saturating maximum current. At high concentrations, both GABA and pentobarbitone could also potentiate the pentobarbitone- and GABA-induced ICl respectively, while pre-treatment with one of the two markedly attenuated currents induced by the other, indicating a 'cross desensitization'. In the presence of pentobarbitone, the augmented response was voltage dependent and this augmentation was much greater in the inward-current direction than outward. In producing ICl, pentobarbitone and its stereoisomers were potent in the order of (-) isomer greater than (+/-) racemic mixture greater than (+) isomer. A stereospecific facilitatory action of pentobarbitone on GABA responses was also found in the same order. Responses to GABA, homotaurine, taurine, beta-alanine, 5-aminovaleric acid, (+)- and (-)-gamma-amino-beta hydroxybutyric acid and muscimol were equally enhanced by pentobarbitone, though its action on glycine-induced ICl was less effective. Picrotoxin inhibited the GABA- and pentobarbitone-induced ICl from either side of membrane, while internal application of GABA and pentobarbitone did not exert any effect. It was concluded that pentobarbitone binds to the 'barbiturate receptors' located close to the GABA receptor-Cl- channel complex, and directly affects the GABA-GABA receptor interactions rather than the ionic channels. PMID- 2580972 TI - Voltage and ion dependences of the slow currents which mediate bursting in Aplysia neurone R15. AB - The previous paper described a slow depolarizing tail current, ID, and a slow hyperpolarizing tail current, IH, that are activated by action potentials and by brief depolarizing pulses in Aplysia neurone R15. ID and IH are necessary for the generation of bursting pace-maker activity in this cell. In this paper, the voltage and ion dependence of ID and IH are studied in an effort to determine the charge carriers for the two currents. When the slow currents are activated by brief depolarizing pulses delivered under voltage clamp in normal medium, an increase in the size of the pulse of 5-10 mV is usually sufficient to bring about full activation of ID. The apparent threshold in normal medium is approximately 20 mV. In medium in which K+ channels are blocked, full activation of an inward tail current that resembles ID requires increasing the pulse amplitude by only 1 2 mV. In contrast, IH is activated in a graded fashion over a 40 mV range of pulse amplitudes. After activating the currents with action potentials or with supramaximal pulses, ID remains an inward current and IH an outward current over a range of membrane potentials spanning -20 to -120 mV. In normal medium, ID is dependent on both extracellular Na+ concentration ( [Na+]o) and extracellular Ca2+ concentration ( [Ca2+]o). When K+ channels are blocked, ID can be supported by either [Na+]o or [Ca2+]o. IH depends only on [Ca2+]o as long as [Na+]o is at least 50 mM. Neither ID nor IH is decreased by decreasing the K+ gradient or by application of K+ channel blockers. These treatments increase somewhat the apparent amplitude of ID, probably by unmasking it from the large K+ tail current that follows the depolarizing pulse. A direct comparison in the same cell of the tetraethylammonium sensitivity of IH and of the Ca2+-activated K+ current demonstrates that these two currents flow through separate and distinct populations of channels. We conclude that in R15, ID arises in response to the triggering of an axonal action potential which in turn, through an as yet unknown mechanism, causes an increased influx of Na+ and/or Ca2+. We conclude that the apparent outward current IH, which is responsible for the interburst hyperpolarization in a normally bursting R15, in fact arises from a decrease in a resting inward Ca2+ current, possibly as the result of Ca2+-induced inactivation of Ca2+ channels. PMID- 2580973 TI - Blockade of slow excitatory post-synaptic potential by substance P antagonists in guinea-pig sympathetic ganglia. AB - The effects of three substance P (SP) antagonists on the inferior mesenteric ganglion of the guinea-pig were studied using intracellular recording techniques, and the possible role of SP as a transmitter for the non-cholinergic slow excitatory post-synaptic potential (e.p.s.p.) was examined. The SP antagonist, [D Arg1, D-Pro2, D-Trp7,9, Leu11]SP, exerted a depolarizing action on the ganglion cells when applied by perfusion at a concentration of 3-16 microM or by pressure ejection from a micropipette. This depolarizing action is probably due to a release of endogenous histamine because it was abolished by treatment with a histamine antagonist, mepyramine (1-3 microM), or by a repeated application of the antagonist. When applied by pressure ejection, SP at 0.5-1 microM depolarized the ganglion cells. In the presence of mepyramine, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP suppressed the SP-induced depolarization by 41% at a concentration of 8 microM and by 75% at 16 microM. By contrast the SP antagonist did not affect the depolarizing action of angiotensin II on the ganglion cells. The non-cholinergic slow e.p.s.p. evoked in the ganglion cells by repetitive stimulation of the lumbar splanchnic nerves was suppressed by [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP at 8 or 16 microM. The degrees of suppression of both the non-cholinergic slow e.p.s.p. and the SP-induced depolarization by the SP antagonist were approximately equal. The cholinergic fast e.p.s.p. evoked by preganglionic nerve stimulation was not affected by the SP antagonist. [D-Pro2, D-Trp7,9]SP exhibited the properties of an SP antagonist similar to, but slightly weaker than [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP. [D-Pro2, D-Phe7, D-Trp9] at a concentration of 16 microM had a depolarizing action on the ganglion cells, which was not blocked by mepyramine. The peptide exerted hardly any antagonistic action against the SP induced depolarization of the ganglion cells. Stimulation of the other preganglionic (intermesenteric) nerves and the post-ganglionic (colonic and hypogastric) nerves produced a non-cholinergic slow e.p.s.p. in the inferior mesenteric ganglion cells. The non-cholinergic slow e.p.s.p. evoked by both pre- and post-ganglionic nerve stimulation were depressed by [D-Arg1, D-Pro2, D Trp7,9, Leu11]SP to similar extents. The present results show that [D-Arg1, D Pro2, D-Trp7,9, Leu11]SP and [D-Pro2, D-Trp7,9]SP can serve as specific SP antagonists in the inferior mesenteric ganglion of the guinea-pig.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2580975 TI - Membrane current noise in toad retinal rods exposed to low external calcium. AB - Outer segment membrane current of single rod photoreceptors from toad retina was recorded with a suction electrode, and extracellular calcium concentration was manipulated by transferring the recorded cell from one pool of saline to another or by locally perfusing the outer segment. The large increase in dark current that resulted from exposure to low-calcium saline was accompanied by an increase in dark noise in the band 1-800 Hz. This noise was suppressed by bright light, and its power spectrum could be described by a single Lorentzian equation with average corner frequency of 40.1 +/- 9.5 Hz (mean +/- S.D., n = 11). In low calcium saline, saturating flash responses were often followed by a transient increase in the dark current lasting 30-100 s. During this rebound period of increased dark current, increased dark noise similar to that described in 2 was observed. The power spectrum of this noise was also fitted by a single Lorentzian equation, with corner frequency averaging 29.7 +/- 6.6 Hz (mean +/- S.D., n = 27). To examine the possible role of intracellular voltage fluctuations in generating the noise, suction electrodes were filled with calcium-free saline and recordings were made from outer segments of rods attached to pieces of retina. In this recording configuration, the electrical coupling among the rods in the piece should attenuate voltage fluctuations associated with the post-light rebound period of increased dark current. In this situation, the rebound increase in dark current was still observed, but the noise was reduced or absent. Using the same recording configuration, isolated rods showed pronounced noise during the rebound. The result in 4 suggests that the noise resulted from fluctuations in intracellular voltage, not directly from fluctuations in the light-sensitive channels. In this view, the corner frequency of the noise power spectrum probably reflects the membrane time constant of the isolated rod. PMID- 2580974 TI - Noradrenaline hyperpolarization and depolarization in cat vesical parasympathetic neurones. AB - Responses to noradrenaline (NA) applied by superfusion, ionophoresis or pressure pulse were analysed using conventional intracellular recording and voltage-clamp methods in cat vesical parasympathetic ganglia. NA (1 microM) hyperpolarized 60% of the neurones, depolarized 25%, and produced a biphasic potential, which comprised a membrane hyperpolarization followed by a membrane depolarization, in 10%. About 5% of the neurones did not respond to NA. The NA hyperpolarization was blocked by yohimbine (1 microM), an alpha 2-adrenoceptor antagonist, whereas the NA depolarization was blocked by prazosin (0.1-1 microM), an alpha 1-adrenoceptor antagonist. These data indicated that the NA hyperpolarization was mediated through alpha 2-adrenoceptors and the NA depolarization through alpha 1 adrenoceptors. The NA hyperpolarization was accompanied by an increase in conductance, while the NA depolarization was associated with a decrease in conductance measured under manual-clamp conditions. Similar conductance changes were observed under voltage clamp. NA hyperpolarizations became smaller as the membrane was hyperpolarized and reversed polarity beyond -100 mV. NA depolarizations also became smaller at hyperpolarized membrane potentials and reversed polarity around -90 mV. The NA responses were enhanced in low-K media and depressed in high-K Krebs solution. The NA hyperpolarization was blocked by the Ca antagonists, Cd, Mn and Co. Intracellular injection of EGTA caused a slowly developing, progressive block of the NA hyperpolarization. The NA depolarization was not affected by low Ca concentrations, Ca antagonists or intracellular injection of EGTA. In some neurones the NA depolarization was unmasked in solutions containing Ca antagonists and after intracellular EGTA injection. The NA hyperpolarization was depressed by intracellular injection and extracellular superfusion of Cs but not by TEA. Ba (10-100 microM) depressed the NA hyperpolarization by 30%. The NA depolarization persisted in the presence of muscarine (10 microM) and was not blocked by Cs or TEA but was depressed 70% by Ba (10 microM). These data are consistent with the hypotheses that alpha 2 adrenoceptor activation produces a membrane hyperpolarization that is mediated through a Ca-dependent K conductance, and that alpha 1-adrenoceptor activation produces a membrane depolarization through closure of a voltage-insensitive K channel. PMID- 2580976 TI - Calcium channels and intracellular calcium release are pharmacologically different in frog skeletal muscle. AB - The pharmacology of Ca2+ channels and intracellular Ca2+ release from the sarcoplasmic reticulum (s.r.) were compared by injecting Ca2+ channel blockers into the cytoplasm and observing contraction under voltage clamp of frog skeletal muscle fibres, a preparation that contracts only in response to Ca2+ release from the s.r. A method for quantifying intracellular injections by co-injecting a fluorescent dye is described. Nifedipine injected into cells blocks Ca2+ current through the cell membrane showing that nifedipine is active when applied to the cytoplasmic side of the membrane in which Ca2+ channels are located. Neither the presence of Ca2+ channel blockers in the extracellular medium nor 24 h incubation in nifedipine and D-600 affect contraction. Nifedipine and D-600 injected to intracellular concentrations much greater than necessary to block Ca2+ channels do not affect contraction. The presence of 30 microM-D-600 during K+ contractures caused paralysis but 20 microM-nifedipine did not. Thus, contracture-dependent D 600 paralysis is not due to blockade of the transverse tubule Ca2+ channel. It is concluded that: (a) a functioning Ca2+ channel on the cell membrane is not necessary to trigger Ca2+ release from the s.r.; (b) s.r. Ca2+ release and Ca2+ channels are pharmacologically different. PMID- 2580977 TI - The early time course of potassium-stimulated calcium uptake in presynaptic nerve terminals isolated from rat brain. AB - K-stimulated (voltage-dependent) 45Ca uptake in rat brain synaptosomes was measured at times ranging from 0.1 to 10 s, in experiments that employed a rapid mixing device to initiate and terminate radiotracer uptake. The rapid mixing did not disrupt the functional integrity of the synaptosomes, as judged by their ability to take up Ca. In solutions containing a low (0.02 mM) concentration of Ca, the rate of K-stimulated Ca uptake measured after 0-0.12 s depolarization was 8 times greater than that measured after 5-10 s of depolarization. The decline in rate of K-stimulated Ca uptake was not due to tracer backflux from the synaptosomes, nor to Ca loading of the nerve terminals, since it also occurred after synaptosomes were depolarized in solutions without Ca. It is suggested that this decline in rate of Ca uptake after depolarization was due to inactivation of voltage-dependent Ca channels in the nerve terminals. This inactivation appeared to be voltage rather than Ca dependent. The extent to which K-stimulated Ca uptake declined after depolarization in high-K solution depended on the K concentration that was used to depolarize the synaptosomes. Whereas pre incubation in solution with one-half of the Na replaced by K significantly reduced subsequent K-stimulated Ca uptake, pre-incubation in non-depolarizing solution, with one-half of the Na replaced by choline, had no significant effect on subsequent K-stimulated Ca uptake. In solutions containing a high (0.5-2 mM) concentration of Ca, the rate of K-stimulated Ca uptake measured after 0-0.12 s was 40 times greater than that measured after 5-10 s. High Ca accelerated the rate at which K-stimulated Ca uptake declined with prolonged depolarization. The effect was mimicked by high (10 mM) concentrations of Sr, but not of Ba. The accelerated rate of decline observed with high Ca could be either a direct effect of Ca on the Ca channels or, more probably, an indirect effect of Ca loading on the nerve terminals. The apparent efficacy of several Ca-channel blockers (Ni, La and verapamil) in reducing K-stimulated Ca uptake was enhanced when the synaptosomes were depolarized in the presence of inhibitory agents for brief (less than 1 s) intervals before K-stimulated Ca uptake was measured. PMID- 2580978 TI - The calcium current in a myenteric neurone of the guinea-pig ileum. AB - The active and passive electrical properties of the after-hyperpolarizing (AH) cell of the guinea-pig myenteric plexus were analysed using a single-electrode voltage or current clamp. Action potentials were compared under normal conditions, in the presence of tetrodotoxin (TTX) and in the presence of both TTX and tetraethylammonium chloride (TEA). Calcium action potentials were studied by examining their calcium dependence, the actions of manganese and the effect of substituting barium for calcium. The maximum rate of rise of the action potential did not increase in calcium concentrations above 10 mM. The half-saturation concentration was 2 mM-calcium. AH cells exhibited five predominant currents consisting of an inward sodium current, an inward calcium current and three outward currents. There was a transient outward current which was inactivated at holding potentials more positive than -65 mV and was suppressed by 4 aminopyridine and barium but not by external TEA. A second outward current observed in the presence of 10 mM-external TEA had properties consistent with that of the delayed rectifier (Hodgkin & Huxley, 1952). A third outward current was the calcium-dependent slow after-hyperpolarizing current (Hirst, Johnson & van Helden, 1985). The voltage dependence, the action of calcium antagonists, the effect of barium substitution and the temporal characteristics of calcium currents were studied. The peak calcium current density was in excess of 100 microA/cm2 in 2.5 mM-calcium solution at 35 degrees C for depolarizations to -10 mV. Calcium currents showed at least two phases of inactivation. Both calcium and barium currents showed early inactivation with decay occurring over the first 10 40 ms. The calcium-activated current precluded direct measurement of slow inactivation of the calcium current. Barium currents studied over the first 100 150 ms had a very slow inactivating component. PMID- 2580979 TI - The slow calcium-dependent potassium current in a myenteric neurone of the guinea pig ileum. AB - Experiments were performed in current-clamped and voltage-clamped after hyperpolarizing (AH) neurones of the guinea-pig myenteric plexus to examine the properties of the potassium conductance (gK, Ca) underlying the slow calcium activated after-hyperpolarization (VK, Ca). The action potential plateau lengthened by the addition of tetraethylammonium chloride (TEA) to the bathing medium was compared to VK, Ca. Results were consistent with enhanced calcium entry causing an increase of VK, Ca. 4-Aminopyridine (4-AP) directly reduced VK, Ca. Voltage-clamp data of gK, Ca were well fitted by a process with a delay (approximately equal to 60 ms) followed by exponential activation (time constant approximately equal to 300 ms) and inactivation (time constant approximately equal to 2 s). The presence of a small, much slower inactivating process was noted. Values for time constants were similar to those reported by Morita, North & Tokimasa (1982) and North & Tokimasa (1983) where gK, Ca was measured during VK, Ca subsequent to action potential stimulation. The relation between gK, Ca (or the calcium-activated potassium current IK, Ca) and estimated calcium influx resulting from short-duration calcium currents elicited at various voltages was compared. Both the integral of the calcium current and gK, Ca showed a similar dependence on the depolarizations used to elicit IK, Ca except there was a positive shift of about 4 mV for the gK, Ca curve. This shift was attributed to a requirement for calcium ions to prime the gK, Ca mechanism. An inward ion charge movement of about 8 pC was required before significant activation of gK, Ca occurred. After the 'priming' condition had been established, the sensitivity of gK, Ca to inward calcium current measured at the resting potential was about 500 pS/pC of inward charge. Large calcium entry obtained by prolonged calcium currents caused saturation of the peak amplitude of IK, Ca and initiated currents with slower time to peak amplitude and longer duration. Increasing the calcium concentration of the external solution provided proportionally larger IK, Ca currents before saturation. The saturation amplitude of IK, Ca (namely gK, Ca) was relatively unaffected. PMID- 2580980 TI - Evidence for two transient sodium currents in the frog node of Ranvier. AB - Na current (INa) was monitored in isolated voltage-clamped frog nodes of Ranvier in order to analyse the pharmacological and kinetic properties of fast and slow phases of inactivation. Niflumic acid (0.1-10 mM) and tetrodotoxin (0.3-30 nM) did not alter fast and slow inactivation time courses but preferentially reduced the amplitude of the fast phase of inactivation. The block of both phases of inactivation by niflumic acid and tetrodotoxin was well described if one assumed that more than one molecule of drug reacted with one channel. Fast and slow currents, corresponding respectively to fast and slow phases of inactivation, reversed at different potentials, had different threshold voltages of activation and the slopes of their steady-state inactivation curves were different. The recovery from inactivation of the compound INa could be described by the sum of two exponentials (plus a delay) corresponding respectively to fast and slow currents. When calculated from INa recorded without and with niflumic acid or tetrodotoxin, the slow current activated about three times more slowly than the fast current. Large prehyperpolarizations delayed both the activation and the inactivation of the fast current but only the activation of the slow current. Lowering the temperature decreased the fast current but increased the slow current. We conclude that the inactivatable Na current of the nodal membrane is made up of two components (INa,f and INa,s) corresponding to two different and interconvertible forms of the Na channel. PMID- 2580982 TI - Calcium-activated potassium channels in isolated presynaptic nerve terminals from rat brain. AB - 86Rb efflux was examined in isolated presynaptic nerve terminals (synaptosomes) from rat brain in a study designed to assess K permeability (PK) changes sensitive to alterations in internal Ca activity. Rb efflux from 86Rb-loaded synaptosomes into nominally Ca-free physiological saline (PSS) containing 5 mM-K was about 0.3-0.4%/s. Raising extracellular K concentration [( K]o), to depolarize the synaptosomes, stimulated the 86Rb efflux. Addition of Ca to the 5 mM-K PSS had no effect, but Ca did further stimulate 86Rb efflux into K-rich solutions. The effect of Ca was graded, with apparent half-maximal activation, KA approximately equal to 0.5 mM-Ca. These data fit the view that, during depolarization, Ca enters the terminals through voltage-regulated Ca channels, and that the rise in intracellular Ca concentration opens certain (Ca-activated) K channels. The Ca-dependent stimulation of 86Rb efflux was greatest during the initial seconds of incubation (component CT), and then declined to a much lower rate (component CS). Much of this change in rate could be attributed to inactivation of voltage-regulated Ca channels and reduced entry of Ca. The Ca dependent increase in 86Rb efflux was completely inhibited by 100 microM-La. In the presence of Ca, but not in its absence, the Ca ionophore A23187 stimulated 86Rb efflux both in 5 and 100 mM-K PSS. The effect in 100 mM-K was quantitatively greater, perhaps because of the increased outward driving force on Rb in depolarized synaptosomes. When synaptosomes were suspended in media containing the voltage-sensitive fluorescent dye, DiS-C3-(5) (1,1'-dipentyl-2,2' thiocarbocyanine), the addition of Ca+ A23187 decreased the fluorescence intensity (= synaptosome hyperpolarization) when the media contained 5 mM-K but not 100 mM-K. This implies that in the presence of Ca + A23187, PK was increased, and the membrane potential moved closer to the K equilibrium potential, EK. Quinine sulphate, a blocker of Ca-activated K channels, reduced the Ca-stimulated 86Rb efflux with high affinity (apparent half-maximal inhibition, KI approximately equal to 1 microM). Tetraethylammonium chloride, another agent known to block Ca-activated K channels, was also a relatively potent inhibitor of Ca-stimulated 86Rb efflux (KI approximately equal to 0.2 mM). The K-channel blocker, 4-aminopyridine, partially inhibited Ca-stimulated 86Rb efflux at concentrations below 0.5 mM, but stimulated this efflux at concentrations greater than or equal to 1 mM.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2580981 TI - Potassium channels in isolated presynaptic nerve terminals from rat brain. AB - 86Rb efflux from pinched-off rat brain presynaptic nerve terminals (synaptosomes) was used to measure the K permeability of the terminals. Synaptosomes were pre loaded with 86Rb and the suspensions were then filtered on glass fibre filters. The terminals trapped on the filters were superfused with 'efflux solutions', and the effluent and filters were then counted. 86Rb efflux into physiological saline (PSS) containing 5 mM-K and 145 mM-Na was about 0.4% of the 86Rb load per second (component 'R'). Increasing extracellular K concentration [( K]o), or adding veratridine and sea anemone toxin, stimulated efflux; presumably by depolarizing the nerve terminals. The K-stimulated 86Rb efflux was a graded function of [K]o. High [K]o evoked at least three components of efflux: a 'fast phase' (T) that apparently inactivated in less than 1 s, a 'slower phase' (S) that was linear for 3-5 s, and a Ca-dependent phase (C). Some, but not all, of the slow phase 86Rb efflux (component S) may be attributable to increased efflux mediated by the 'resting' K permeability mechanism when the driving force is increased by depolarization. K efflux was also studied and was found to be qualitatively similar to 86Rb efflux. 86Rb: 42K permeability ratios were 0.6-0.8 for most components of the efflux. Raising the Mg concentration in the efflux solution shifted the 86Rb efflux versus [K]o curve in the direction of increased [K]o. This shift may be the result of screening of surface charges by Mg. Several agents that block various K channels in other preparations inhibited K-stimulated 86Rb efflux in synaptosomes: tetraethylammonium (TEA), tetrabutylammonium (TBA), and 4-aminopyridine (4-AP). The fast component (T) of high [K]o-stimulated 86Rb efflux was selectively blocked by low concentrations of 4-AP (apparent half maximal inhibition, KI = 0.1-0.2 mM); it was also blocked by TEA (KI = 0.6 mM) and TBA (KI = 0.8-1.0 mM). Dose-response curves for inhibition of component T by all three agents were monophasic. the slow component (S) of the K-stimulated 86Rb efflux was much less sensitive to all three agents, than was component T; the broad dose-response curves were consistent with the view that two (or more) different K conductances may contribute to component S.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2580985 TI - Revitalizing defaced maxillary plastic denture teeth with resin stain. PMID- 2580983 TI - Dual effects of internal n-alkyltrimethylammonium ions on the sodium current of the squid giant axon. AB - The actions of members of the homologous series of alkyl cations CH3 (CH2)n-1 N+ (CH3)3 (Cn TMA) on the sodium current in giant axons of Loligo forbesi have been investigated. The substances tested correspond to n = 6, 8, 10, 12, 14 and 16. These cations only produced significant sodium current suppression when applied inside the axon. Actions on first-pulse sodium currents and use-dependent effects were separately studied. The shorter members of the series (C6TMA and C8TMA) produced suppression of first-pulse sodium currents without causing significant use dependence. The first-pulse suppression arose partly from a positive shift along the voltage axis of the steady-state activation parameter (m infinity) and partly from a reduction in the maximum sodium conductance (gNa). C12TMA and C14TMA produced little first-pulse suppression but caused clear use dependence. C10TMA showed intermediate properties while C16TMA was inactive. The use dependent actions have been quantitatively investigated using a double-pulse protocol. The results are consistent with a model in which the cations enter a blocking site on the ion-channel via the intra-axonal aqueous phase. The cations appear able to bind to inactivated sodium channels at significant rates. The possible molecular locations of the sites responsible for m infinity shifts and use dependence are discussed. It is argued that the existence of two separate sites may help to explain certain distinctions between the actions of neutral general anaesthetics and clinical local anaesthetics on the sodium channel. PMID- 2580986 TI - A Celestin bubble. An unusual cause of obstruction. PMID- 2580984 TI - The action of N-methyl-D-aspartic acid on mouse spinal neurones in culture. AB - Neurones from the ventral half of mouse embryo spinal cord were grown in dissociated culture and voltage clamped. The current-voltage relation of responses evoked by N-methyl-D-aspartic acid (NMDA), L-glutamic acid and kainic acid was recorded in media of different ionic composition. On removal of Mg2+ from the extracellular solution, responses to NMDA and L-glutamate became less voltage sensitive, such that NMDA responses were no longer associated with a region of negative slope conductance. The antagonism of NMDA responses produced by application of Mg2+ to neurones bathed in nominally Mg2+-free solutions shows voltage dependence and uncompetitive kinetics. Voltage-jump experiments showed that the voltage-dependent action of Mg2+ occurred rapidly, and with complex kinetics. Ni2+ and Cd2+, two potent blockers of calcium currents in spinal cord neurones, had significantly different potencies as NMDA antagonists, Ni2+ being of greater potency than Mg2+, and Cd2+ considerably weaker. The voltage-dependent block of NMDA responses produced by physiological concentrations of Mg2+ is sufficient to explain the apparent increase in membrane resistance produced by NMDA in current-clamp experiments, and the ability of NMDA to support repetitive firing. Substitution of choline for Na+ produced a hyperpolarizing shift in the reversal potential for responses evoked by kainic acid consistent with an increase in permeability to Na+ and K+. In choline-substituted solutions, the reversal potential of NMDA responses was more positive than that recorded for kainic acid, and in addition NMDA responses showed enhanced desensitization. PMID- 2580987 TI - Separation of inherent diastolic myocardial fiber tension and coronary vascular erectile contributions to wall stiffness of rabbit hearts damaged by ischemia, hypoxia, calcium paradox and reperfusion. AB - Ischemic myocardial contracture is exacerbated by reperfusion. This study examines the extent to which intensification of contracture by reperfusion is due to metabolic reoxygenation phenomena or hydraulic erectile contributions of coronary perfusion to left ventricular (LV) stiffness. Isolated rabbit hearts, with fluid-filled LV intraventricular baloons, were subjected either to: control aerobic perfusion; 30 or 60 min of global ischemia; 60 min of hypoxia with constant coronary flow; or 10 min of calcium-free perfusion to cause calcium paradox injury. During reperfusion with control perfusate isovolumic LV end diastolic pressure (LVEDP) was measured with constant coronary flow and during transient, 1 min, total global ischemia to measure the contribution of the coronary perfusion to LVEDP. In all injured groups LVEDP was increased compared to control hearts. The decrease in LVEDP during transient ischemia was greater in damaged hearts than in controls, demonstrating a greater contribution of coronary perfusion to LVEDP after injury. Only in the hypoxic hearts did diastolic fiber tension increase upon reperfusion. Inherent diastolic fiber tension decreased during 15 to 60 min of reperfusion in the ischemic and hypoxic injury groups, a trend which was masked by an increasing effect of coronary perfusion on LV chamber stiffness. During the reperfusion period enhancement of the erectile effect was more pronounced at higher preloads. Thus, reperfusion contracture was maintained both by changes in inherent fiber stiffness and by changes in the erectile effect. These contributions changed over time and varied with the type and severity of injury, but after all types of injury the erectile vascular effect made a greater contribution to diastolic chamber stiffness than inherent fiber tension. PMID- 2580989 TI - Myelin basic protein-responsive blood T lymphocytes in patients with multiple sclerosis. AB - Previous studies from our laboratory showed the development of circulating T lymphocytes sensitized to myelin basic protein (MBP) in guinea pigs challenged with MBP. Also, lymphocytes sensitized to MBP were found in patients with multiple sclerosis (MS). In this report, we describe the kinetics of MBP sensitized lymphocytes in a longitudinal study (140-316 days) of seven MS patients using the MBP-stimulated active rosette-forming T cell assay (MBP-ARFC). Expressed as the ratio of MBP-ARFC over ARFC (early and 37 degrees C stable rosette-forming T lymphocytes without added antigen), the results show a considerable degree of variation in the levels of MBP-ARFC. Although the levels of ARFC during the study period were relatively unchanged for each patient, increases in the MBP-ARFC/ARFC ratios were associated with the development of neurological symptoms of disease. The results of this study demonstrate the development of T-cell-mediated immunity to MBP in patients with MS. Detection of MBP-sensitive cells was possible during the course of the disease. The level of sensitivity was influenced by the clinical status, degree of neurological deficit, and particular treatment course. PMID- 2580988 TI - Interactions of amantadine with the cardiac muscarinic receptor. AB - The antiviral drug amantadine has anticholinergic effects in the guinea-pig atrium at concentrations greater than 1 X 10(-4)M. It is a competitive inhibitor of [3H]-quinuclidinyl benzilate binding to the muscarinic receptor, but antagonizes the negative inotropic effect of acetylcholine in a non-competitive manner. It increases the duration of the atrial action potential and also increases the force of atrial contraction. These effects are evident at approximately 10 times lower concentrations than the antimuscarinic effects. The increase in contractility can be reversed by propranolol (5 X 10(-7)M) but the increase in action potential duration is potentiated by propranolol. Shortening of the action potential duration by acetylcholine was reversed by amantadine, but at approximately ten times lower levels than were needed to reduce the negative inotropic effect. Interactions between beta adrenoceptor binding of [3H] dihydroalprenolol and amantadine could not be demonstrated. Similarly, binding of [3H]-nitrendipine to the calcium channel is not influenced. It is suggested that amantadine may exert its positive inotropic effect by interaction with the potassium channel, causing a delay in outward current. PMID- 2580991 TI - Crowbar impalement of the brain. AB - The management of impaled foreign objects is always a challenge. Stabilization of the object, control of hemorrhage, and adherence to the basic principles of airway and breathing control are hallmarks of prehospital management. Once the patient is in the hospital, a careful assessment of the involved vital structures is essential before removal is attempted. A penetrating injury to the left hemisphere of the brain with a crowbar is presented. This case demonstrates the characteristics of these injuries in terms of extrication, assessment, management of complications, and neurologic sequelae. PMID- 2580990 TI - An immunochemical investigation of 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in bovine cerebrum and human oligodendroglioma. AB - Bovine cerebrum, including the corpus callosum, and a human oligodendroglioma were investigated by an immunohistochemical technique to determine the distribution of 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNP). Also, three human oligodendrogliomas (ODG) were characterized by an immunoblot procedure to identify a protein(s) with cross-reacting determinants to CNP and assayed for CNP activity. CNP was localized to oligodendrocytes in the corpus callosum and subcortical white matter and gray matter. Also, nerve fibers appeared to be stained. Further, cells of the human oligodendroglioma were immunostained which were similar in morphology to those cells stained in the bovine cerebrum; however, fewer than 5% of the oligodendroglioma cells were immunostained. Immunoblotting revealed two separate and distinct bands for the three oligodendrogliomas, showing cross-reactivity to bovine CNP antisera at about 53,000 and 46,000 daltons. Specific CNP activity of the three human oligodendrogliomas ranged from 0.4 to 1.6 mumole of 2':3'-cAMP hydrolyzed/min/mg protein. PMID- 2580992 TI - Sonographic patterns of pelvic and hepatic lesions in persistent trophoblastic disease. AB - The sonographic findings of the pelvic lesions in persistent trophoblastic disease were evaluated prospectively in 57 patients. The appearance ranged from minimal lesions in the myometrium to complex lesions extending into the parametrium. A grading system was devised based upon the extent of the disease in the pelvis. The different grades correlated well with the plasma human chorionic gonadotrophin level at the time of the ultrasound examination. Findings of the hepatic lesions were evaluated in 69 patients managed during the same period. Thirteen were diagnosed to have metastatic disease on hepatic arteriography, of which 11 were correctly diagnosed by ultrasonography. The sensitivity and specificity of sonography in detecting metastasis in the liver from trophoblastic disease were 86.7 and 91.8 per cent, respectively. Two sonographic patterns were observed: a) the discrete hyperechoic lesions in three patients and b) the diffuse hyperechoic lesions in eight patients. In addition, ultrasonography could depict the size and internal structure of the pelvic and hepatic lesions much better than arteriography. Therefore, it is concluded that sonography is a very useful tool in the assessment of these lesions in persistent trophoblastic disease. PMID- 2580994 TI - Effects of pure interferons on Epstein-Barr virus infection in vitro. AB - Pure human gamma-interferon as well as alpha-interferon inhibited induction of immunoglobulin synthesis by Epstein-Barr virus but not by pokeweed mitogen in B lymphocytes from adult but not from newborn humans. The interferons inhibited the infected B lymphocytes directly, irrespective of the Epstein-Barr virus immune status of the donor, and their inhibitory effect was synergistic. PMID- 2580993 TI - Inhibition of binding to initiation complexes of nascent reovirus mRNA by double stranded RNA-dependent protein kinase. AB - A coupled, cell-free system for the transcription and translation of reovirus mRNA was developed. Activated reovirions were incubated with reticulocyte lysate and an appropriate energy mix. Active transcription was obtained, but protein synthesis was inhibited after a short lag even by low concentrations of reovirions. This inhibition was abolished by the addition of the kinase inhibitor 2-aminopurine. With this addition, the synthesis of viral proteins could be detected in reaction mixtures containing nuclease-treated reticulocyte lysate. The binding of nascent reovirus mRNA to 80S initiation complexes measured after 2 min of incubation was greatly inhibited, whereas the binding of cellular mRNA added to the same reaction mixtures for the next 2 min was not inhibited. The inhibition of reovirus mRNA binding could not be explained by the synthesis of defective templates, since most of the mRNA could be bound to 80S complexes after the addition of 2-aminopurine. These results indicate that the binding of nascent reovirus mRNA was preferentially inhibited by a protein kinase. Reovirions preincubated with reticulocyte lysate could phosphorylate initiation factor eIF 2. This phosphorylation was inhibited by the addition of high concentrations of double-stranded RNA, which are inhibitory for the eIF-2 kinase present in elevated levels in reticulocyte lysate and in interferon-treated cells. These results indicate that the translation of viral mRNA may be preferentially inhibited in interferon-treated cells by the eIF-2 kinase activated by viral transcriptional complexes containing double-stranded RNA. PMID- 2580995 TI - The significance of uninhibited detrusor contractions in prostatism. AB - In an attempt to identify preoperatively patients who will not benefit from prostatectomy, 84 patients with prostatism about to undergo transurethral resection of the prostate were evaluated prospectively with preoperative and postoperative symptom analysis and urodynamic examination, including cystometrograms. Of the patients 67 were followed at 3 months and 54 again at 12 months. Preoperatively, 65 per cent of the patients had uninhibited detrusor contractions, while 38 had persistent postoperative uninhibited detrusor contractions at 3 months. Patients in whom uninhibited detrusor contractions persisted postoperatively more often had unacceptable postoperative symptoms. Of the patients 13 per cent believed the symptoms to be the same or worse at 3 and 12 months. The incidence of uninhibited detrusor contractions in these patients was 57 and 71 per cent, respectively. While this finding suggests that persistent postoperative uninhibited detrusor contractions are associated with an unfavorable surgical outcome, we could not predict which patients would have uninhibited detrusor contractions following prostatectomy by use of preoperative cystometric findings together with detailed symptom analysis. Thus, we failed to define a role for preoperative cystometric screening of patients with prostatism. PMID- 2580996 TI - Lethal complications of standard self-retaining ureteral stents in patients with ileal conduit urinary diversion. AB - While standard commercially available pigtail ureteral stents are used commonly in the obstructed patient, particularly when metastatic disease has been identified, our recent experience suggests caution in the use of such stents for patients with ileal conduits. Rapid obstruction of these stents occurs with unacceptable frequency, which has resulted in urosepsis and death, and they do not appear to be cost-effective even for palliation. Although these standard pigtail stents have physical properties that allow easy placement by angiographic wire guidance, they are not to be recommended. Safe internal ureteral diversion in patients with an ileal conduit awaits further evolution in stent technology. PMID- 2580997 TI - Localized deep microwave hyperthermia in the treatment of poor operative risk patients with benign prostatic hyperplasia. AB - Non-invasive localized deep microwave hyperthermia was applied as an alternative treatment to surgery in 29 patients with contraindications for prostatectomy. Patients were treated twice weekly, on Mondays and Thursdays, for 1 hour, without sedation on an outpatient basis. All patients tolerated treatment well without secondary effects. The results indicate that localized deep microwave hyperthermia applied by this method is safe and effective in the treatment of benign prostatic hyperplasia. PMID- 2580998 TI - Immunocytochemical demonstration of prostatic acid phosphatase: different secretion kinetics between normal, hyperplastic and neoplastic prostates. AB - The ultrastructural localization and distribution of prostatic specific acid phosphatase in normal, hyperplastic and neoplastic human prostates was studied by immunocytochemical methods. In normal or hyperplastic prostates, the localization of prostatic specific acid phosphatase was uniformly observed at the apical portion of the glandular epithelium of apical cells under the light microscope. Electron microscopy revealed prostatic specific acid phosphatase localized in the microvilli lining prostatic and vesicular bodies of apical cells. Occasionally the limiting membrane of the blebs and vesicles extruded into the glandular lumen and were stained positively. Light microscopic examination of neoplastic prostates revealed a more intense and uniform staining of tumor cells and the glandular epithelium of well differentiated adenocarcinomas, whereas less intense and more variable staining was seen in neoplastic cells of moderately or poorly differentiated adenocarcinomas. Furthermore, under electron microscopic study, prostatic specific acid phosphatase granules were uniformly and intensely condensed in intracytoplasmic vacuoles in well differentiated adenocarcinomas, whereas in moderately or poorly differentiated adenocarcinomas 2 types of staining were observed. Among neoplastic cells, positive granules with less intensity were found between collagen fibers as well as adjacent to the endothelium of the stromal capillaries in anaplastic tissue. PMID- 2580999 TI - [Combination chemotherapy with cis-dichlorodiammineplatinum (11) (CDDP) and bleomycin BLM in advanced esophageal carcinoma]. AB - Five patients with advanced carcinoma of the esophagus were treated with a combination chemotherapy employing CDDP and BLM. One cycle of chemotherapy consisted of CDDP, 50 mg/m2, on day 1 and BLM, 15 mg/patient on days, 1, 7 and 14. Two partial remission and 2 minor responses were obtained. Overall response rates, ths, were 80%. The most adverse effect was nausea. No significant elevation in the serum creatinine or BUN was recognized. Furthermore, the method of CDDP administration was studied on the serum level by 15 minutes' infusion and by 24 hours continuous infusion. The CDDP levels in the serum and tissue were determined by flameless atomic absorption spectrophotometry. The CDDP level in the serum by 15 minutes' infusion was higher than that by 24 hours continuous infusion. These results suggest that combination chemotherapy with CDDP and BLM may be a useful method for the treatment of advanced esophageal carcinoma. PMID- 2581000 TI - [Simultaneous production of amylase and adrenocorticotropin by lung cancer--with special reference to electron microscopic and immunohistochemical studies]. AB - The tumor tissue from a lung cancer patient who showed elevated serum amylase and adrenocorticotropin was investigated ultrastructurally and immunohistochemically. On microscopic examination, the tumor was diagnosed as small-cell carcinoma. Electron microscopy revealed that some of the tumor cells possessed small endocrine-like dense cored granules. The tumor cells also contained large zymogen like granules within the cytoplasm, which possessed microvilli and formed the lumen, indicating their adenocarcinomatous differentiation. An electrophoretic analysis of the serum amylase showed that the major amylase elevated was of the salivary type. Immunohistochemical staining by the antihuman salivary amylase antibody disclosed that various portions of the tumor actually contained the salivary amylase. The evidence suggests that the small-cell carcinoma cells showed "confused differentiation", thereby expressing amylase and ACTH simultaneously. PMID- 2581001 TI - [Adenomatoid tumor of the uterus--a light-microscopical, electronmicroscopical, histochemical and immunohistochemical study]. AB - A 34-year-old woman with an adenomatoid tumor of the uterus is reported. Light microscopic examination showed the tumor to be cystic with a canalicular pattern. The ultrastructural findings were numerous microvilli, various intercellular spaces, desmosomes, and rich 10-nm microfilaments like tonofilament. Histochemically, the tumor cells secreted hyaluronic acids. Keratin was demonstrated diffusely in the cytoplasms of tumor cells by PAP staining. From these findings, we concluded that the histogenesis of the adenomatoid tumor was of mesothelial origin. PMID- 2581002 TI - [Progress of research on HLA and transplantation immunology, with special reference to class II antigen compatibility and DR antigen]. PMID- 2581004 TI - [Significance of the granular lymphocyte (NK cells) count in the peripheral blood]. PMID- 2581003 TI - [Relation between ventricular premature contraction frequency and heart rate and analysis of antiarrhythmic effects of calcium channel blockers]. PMID- 2581005 TI - [Characterization of human AFP producing stomach cancer xenotransplanted in nude mice and effect of a conjugate of MMC and antibody to human AFP on this tumor]. PMID- 2581006 TI - [A histochemical study of goblet cell mucin in ulcerative colitis with special reference to time sequence]. PMID- 2581007 TI - Supersensitivity of amylase secretion from rat parotid tissue--its selective nature for the beta 2-adrenergic response. AB - In rat parotid tissue, amylase secretion and accumulation of cyclic AMP were not selective responses to the different beta-subtypes, beta 1 and beta 2. However, the supersensitivity of the amylase secretory response induced by brief pretreatment with beta-agonist was due specifically to a beta 2-adrenergic response. PMID- 2581008 TI - The role of calcium ion in methoxamine-induced amylase release from parotid glands of euthyroid and hypothyroid rats. AB - The change in responsiveness to alpha-adrenergic stimulation and to calcium ions in amylase release from parotid glands of hypothyroid rats was compared with that in euthyroid rats. Calcium depletion and addition of verapamil or W-7 in the medium caused a decrease in methoxamine-induced amylase release in both eu- and hypothyroid rats. Moreover, addition of calcium ions to Ca2+-free medium markedly increased the methoxamine-induced amylase release in proportion to its concentration in hypothyroid rats. These results suggest that calcium ions play an important role in methoxamine-induced amylase release from parotid glands of hypothyroid rats as well as those of the euthyroid ones. PMID- 2581009 TI - [Plastic processes in the myocardium during the use of hyperbaric oxygenation in the recovery period after acute massive blood loss]. PMID- 2581010 TI - Effects of parathyroidectomy on bone formation and mineralization in hemodialyzed patients. AB - Undecalcified sections of doubly tetracycline-labeled transiliac bone biopsy specimens obtained from ten hemodialyzed patients before and 10 to 16 months after parathyroidectomy (PTX) were analyzed. Before parathyroidectomy (total PTX with autotransplant in six patients and subtotal PTX in four patients), all the patients demonstrated histological evidence of hyperparathyroidism with increased resorption parameters. A high bone formation rate (BFR) was noted in all patients but one who had both an increase in the osteoid seam thickness and a low calcification rate characteristic of osteomalacia. A significant correlation was found between immunoreactive parathyroid hormone (iPTH) levels and BFR at the tissue and at the basic multicellular unit (BMU) levels. Parathyroidectomy was associated with a dramatic drop in resorption surfaces and osteoclast number as well as in bone formation rate at the tissue, BMU, and cell-levels. After PTX, the bone formation rate at the tissue level was low or in the lower range of normal values in six patients. The thickness index of osteoid seams was significantly reduced and no evidence of osteomalacia was present even in the six patients showing bone aluminum deposits after PTX. One of the three patients, who had an iPTH level within the normal range after PTX, showed an osteoid excess associated with a low bone formation rate. These date demonstrate that increased PTH secretion is an important factor of bone formation in dialyzed patients and that excessive reduction of the PTH secretion leads to an inactive bone. PMID- 2581011 TI - A role for calcium in radiocontrast-induced reductions in renal hemodynamics. PMID- 2581012 TI - Disorders associated with an altered anion gap. PMID- 2581013 TI - [Method of determining the binding capacity of cAMP-dependent protein kinases]. PMID- 2581014 TI - [Modified determination of reduced nicotinamide coenzymes]. PMID- 2581015 TI - [Determination of kallikrein activity in blood and sputum by a biochemical method]. PMID- 2581016 TI - [Method of determination and diagnostic significance of gastric juice elastase]. PMID- 2581017 TI - [Determination of inorganic phosphorus in blood serum and urine]. PMID- 2581018 TI - [Use of pseudotuberculosis coagglutinating antibody diagnostic agent in laboratory practice]. PMID- 2581019 TI - [Method of determining blood bacteriostatic activity in relation to staphylococci]. PMID- 2581020 TI - [Aggregate-hemagglutination method for the quantitative determination of staphylococcal enterotoxin]. PMID- 2581021 TI - [Dry nutrient medium for determining the lecithinase activity of Bacillus cereus]. PMID- 2581022 TI - [Significance of laboratory values in the diagnostic process]. PMID- 2581024 TI - [Quantitative interpretation of experimental data on cell electrophoresis]. PMID- 2581023 TI - [Homogenization of the sputum for cytologic study]. PMID- 2581025 TI - [Use of mathematical analysis in quantitative determination of immunoglobulins by the radial immunodiffusion method]. PMID- 2581026 TI - [Laboratory requirements for dispensary service to the entire population]. PMID- 2581027 TI - [Cytofluorometric determination of the relation of cell cycle phases in asynchronous populations]. PMID- 2581028 TI - [Evaluation of the effect of drugs on hematopoietic tissue stroma]. PMID- 2581029 TI - [Centrifugal chamber for sedimentation and fixation of bone marrow erythroblastic islets]. PMID- 2581031 TI - [Cytologic characteristics of nephroblastoma]. PMID- 2581030 TI - [Cytomorphological characteristics of basaliomas]. PMID- 2581032 TI - [Diagnosis of precancerous changes in gastric mucosal epithelium during dynamic cytologic observations]. PMID- 2581033 TI - [Use of puncture biopsy in diagnosing the morphofunctional state of the corpus luteum]. PMID- 2581034 TI - [Determination of thrombocyte adhesiveness (retention) using glass beads]. PMID- 2581035 TI - [Method of separating thrombocytes for studying their lipid composition]. PMID- 2581036 TI - [Changes in the hemostatic system during the operative period in patients with lung cancer]. PMID- 2581037 TI - [Thrombocyte aggregation during hormonal treatment of dysfunctional uterine hemorrhage]. PMID- 2581038 TI - [Determination of the heparin dose for preventing thrombohemorrhagic complications caused by amniotic fluid embolism]. PMID- 2581039 TI - [Structure and function of lymphocytes in patients with myopathy]. PMID- 2581040 TI - [Relation of the absorption spectra of DNA-fuchsin to the conditions of carrying out the Feulgen reaction]. PMID- 2581041 TI - [Determination of acridine orange fluorescence in nonfixed peripheral blood lymphocytes]. PMID- 2581042 TI - [Rapid method of determining the phagocytic activity of blood monocytes]. PMID- 2581043 TI - [Middle molecules as uremic toxins (status of the problem)]. PMID- 2581044 TI - [Gas chromatographic vapor-phase analysis of volatile fatty acids in clinical material for rapid diagnosis of anaerobic infections]. PMID- 2581045 TI - [Peptidyl peptidase activity in the blood of healthy children of different ages and patients with pyoseptic diseases]. PMID- 2581046 TI - [Myoglobin content of the blood in patients with lower limb ischemia]. PMID- 2581047 TI - [Dysbacterioses--intestinal infections of mixed etiology]. PMID- 2581048 TI - [Universal stabilizer for erythrocytic diagnostic agents]. PMID- 2581049 TI - [Method for simultaneously determining the requirements of microorganisms for and their ability to synthesize amino acids]. PMID- 2581050 TI - [Determination of the Gram reaction in bacteria without staining the preparations]. PMID- 2581052 TI - [Determination of riboflavin in microquantities of blood]. PMID- 2581051 TI - [Method of determining the sensitivity of lymphocytes to immunomodulators of the phenylimidazothiazole group]. PMID- 2581053 TI - [Method of evaluating the results of studies using the radial immunodiffusion test]. PMID- 2581054 TI - [Possibility of using fiberbronchoscopy for bacterial study of the lower respiratory tract]. PMID- 2581055 TI - [Device for determining the quantity of reagent during treatment of pathological material for isolation of Mycobacterium tuberculosis]. PMID- 2581056 TI - [Apparatus for determining bradykinin by a biological method]. PMID- 2581057 TI - [Device for staining bacterial smear preparations on slides]. PMID- 2581058 TI - [Teaching clinical laboratory diagnosis at institutes of advanced training of physicians]. PMID- 2581059 TI - [Plan for a two-year training of specialists in clinical chemistry]. PMID- 2581061 TI - [Apparatus for microelectrophoresis in capillary tubes]. PMID- 2581062 TI - Identification of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid, an intermediate in cholic acid synthesis, in the plasma of patients with infantile Refsum's disease. AB - The plasma bile acid profiles of three children with the inherited metabolic disorder, infantile Refsum's disease, were found to contain 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid. This intermediate in the synthesis of cholic acid was identified by combined gas-liquid chromatography-mass spectrometry and accounted for approximately 25% of the total bile acids which were present at elevated concentrations in plasma. Infantile Refsum's disease appears to share several biochemical features with the cerebro-hepato-renal syndrome (Zellweger's disease), including abnormal bile acid metabolism. PMID- 2581060 TI - [Quality control of biochemical studies in Grodno Oblast]. PMID- 2581065 TI - Fate of reactive axonal swellings induced by head injury. AB - The fate of those reactive axonal swellings seen following head injury was assessed in cats subjected to mild to moderate fluid-percussion head injury. To allow for the ready visualization of any traumatically induced reactive axonal change at both the light and electron microscopic level, the anterograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase was employed over a 21-day posttraumatic period in selected cerebral and cerebellar efferents coursing through the brain stem. At the designated posttraumatic survival time, the animals were perfused with aldehydes, processed for the light and electron microscopic visualization of the peroxidase reaction product, and examined for any evidence of reactive axonal change. At the 3rd and 4th posttraumatic days, peroxidase-laden swellings could be identified. Some reactive swellings were packed with organelles and were either encompassed by a distended myelin sheath or lacked myelin investment. Other reactive swellings demonstrated either lobulation or increased electron density with macrophage accumulation, all of which indicated degeneration. Wallerian change occurred distal to the reactive swellings; however, with the exception of these changes the related brain parenchyma and vasculature demonstrated no significant abnormality. With continued survival, reactive swellings comparable to those just described were consistently observed; however, now regenerative responses were also seen. At the 5th and 7th days, reactive sprouts were observed originating from reactive swellings which displayed a reduction both in size and in organelle content. By the 9th and 14th posttraumatic days, some sprout-containing swellings demonstrated several robust extensions. These regenerative changes were seen in both myelin- and nonmyelin-invested swellings and persisted through the 21st day, occurring in concert with lobulated, electron dense, and unchanged, swollen reactive axons. This study suggests that head injury elicits axonal swelling that may persist unchanged, degenerate, or undergo a regenerative response. The sustained regenerative responses are considered intriguing and may have relevance both for head-injured humans and for future studies of central nervous system regeneration. PMID- 2581064 TI - Inability of second trimester human amniotic fluid cell cultures to aromatize C19 steroids. AB - Amniotic fluid (AF) and fibroblast (F) cell types, derived from human amniotic fluid by amniocentesis in the second trimester, were cultured using media of varying composition and their ability to transform C19-steroids to oestrogens was investigated by fluorimetry, radioimmunoassay, tritium release and measurement of cytochrome P450. Although the cells were shown to be metabolically active by the presence of mitotic figures, the incorporation of tritiated leucine into protein and the production of the beta-subunit of hCG, no evidence of aromatization was obtained despite the inclusion in the medium of a number of steroids known to be transformed to oestrogens in several in vivo and in vitro preparations. The addition of reported stimulants of aromatase activity, viz. hCG, FSH, diethylstilbestrol, prostaglandins E2 and F2 alpha and dibutyryl cyclic AMP, was without effect. PMID- 2581063 TI - Persistent succinylacetone excretion after liver transplantation in a patient with hereditary tyrosinaemia type I. AB - A liver transplant was performed on a 4-year-old female in liver failure caused by hereditary tyrosinaemia, with hepatocellular carcinoma following a negative evaluation for metastases. However, serum alpha-fetoprotein levels never returned to normal after the surgery. Urinary succinylacetone (SA) was detected in her urine prior to transplantation despite strict adherence to a low-tyrosine diet. Other patients with severe liver disease awaiting liver transplantation do not excrete SA in the urine. She continued to excrete SA during the postoperative period despite normal liver functions. Oral tyrosine loading resulted in significant elevation of SA excretion. Possible explanations for this observation and clinical and therapeutic relevance are discussed. PMID- 2581066 TI - Explant culture of human submandibular gland epithelial cells: evidence for ductal origin. AB - As an approach to investigating the disease cystic fibrosis, attempts were undertaken to culture from human submandibular glands epithelial cells with a potential for manifesting the cystic fibrosis genetic defect. To initiate the culture of submandibular gland epithelial cells, tissue fragments from glands were explanted as a function of both the composition of the serum-free growth medium and of the matrix utilized to coat the culture vessel growth surface. A morphologically homogeneous growth of submandibular gland epithelial cells, uncontaminated by fibroblasts, was obtained, once optimum culture conditions were defined. Light microscopic examination of these explant cultures in a transverse plane of section demonstrated variation in the outgrowth according to distance from the explant. At its outer margin, the outgrowth consisted of one or two layers of viable low cuboidal cells, and more centrally, it was multilayered. Mitotic figures were observed in the periphery of the outgrowth. In the region, a few cells removed from the periphery where the outgrowth consisted of about three to six cell layers, dilated intercellular spaces, indicative of secretion of fluid and ions into the spaces, separated the basal cuboidal cells. Overlying cells were increasingly flattened toward the culture surface and devoid of nuclei. Centrally, near the explant, the multilayer appeared completely involuted throughout. Ultrastructural examination in a transverse plane of the multilayered region with viable basal cells confirmed these observations showing wide spaces separating the cuboidal basal cells, keratinization of midstratum cells, and complete involution of the upper layer of ghost-like cells. These cells cultured from the submandibular gland reacted positively to immunochemical staining for keratin. PMID- 2581067 TI - Lutropin stimulates de novo synthesis of short-lived proteins required for lutropin-dependent steroid production in tumour Leydig cells. AB - Continuous protein synthesis is required for the hormonal regulation of cholesterol side chain cleavage activity. A protein with a short half-life (t1/2 = 2-13 min) is believed to play an important role, but the regulation of the synthesis of this putative rapidly-turning-over protein is largely unknown. The steroid production rate in tumour Leydig cells can be increased more than 4-fold after addition of lutropin. However, steroid production by cells preincubated for 60 min with medium containing cycloheximide (89 microM) could not be stimulated when lutropin was added to the medium. Thus, the putative protein with the short half-life is apparently not derived from a stable precursor protein. Moreover, in tumour Leydig cells incubated with low concentrations of cycloheximide (0.2-0.8 microM), inhibition of steroid production was significantly greater in lutropin stimulated cells than in control cells. These results support the hypothesis that lutropin regulates the de novo synthesis of rapidly-turning-over proteins by increasing the rate of initiation of the translation step of protein synthesis. PMID- 2581068 TI - Changes in plasma steroid levels after single administration of hCG or LHRH agonist analogue in dog and rat. AB - The present study was designed to investigate the effect of acute administration of gonadotropin on testicular steroid secretion in dog and rat. Animals received a subcutaneous injection of 25 IU/kg of hCG or 1.5 microgram/kg of [D-Trp6, des Gly-NH2(10)]LHRH ethylamide (LHRH-A). Testosterone is the predominant steroid measured, in dog plasma, under basal conditions. After LHRH-A injection, testosterone levels are not significantly changed while dehydroepiandrosterone and androst-5-ene-3 beta,17 beta-diol (delta 5-steroids) levels are stimulated by almost 20-fold (P less than 0.01). When dogs were injected with hCG, we also observed a marked stimulation of dehydroepiandrosterone levels (20-fold; P less than 0.01) accompanied by a small increase of plasma testosterone concentration (2-fold, P less than 0.01). In rats injected with either hCG or the LHRH analogue, an increment of plasma testosterone (7-fold, P less than 0.01) is detected in the first hour while plasma dehydroepiandrosterone levels are slightly stimulated. Moreover, in rats injected with hCG, low plasma steroid levels are present between 4-12 h after injection due to testicular desensitization. This marked decrease is then followed by a second peak of steroid secretion 24 h later. Acute testicular steroidogenic responsiveness to hCG on the dog is, however, different: after stimulation, the levels of plasma dehydroepiandrosterone are maintained at a plateau and slowly decline after 24-48 h. Our data indicate that in dogs, stimulation of testicular steroidogenesis leads to an increase of plasma delta 5-steroid levels while the same stimuli cause, in the rat, a stimulation of delta 4-androgen, particularly testosterone. PMID- 2581069 TI - Hydroxylation of [3H]5 alpha-androstane-3 beta,17 beta-diol by whole tissue, epithelial cells and fibroblasts from the same hyperplastic human prostate. AB - Hydroxylations of 3 beta-hydroxy 5 alpha-dihydro C19-steroids are terminal reactions by which male accessory sex organs dispose of intracellular androgens. Cellular androgen egress is of particular interest in benign prostatic hyperplasia (BPH) where the elevated nuclear 5 alpha-dihydrotestosterone-receptor content may be implicated in the etiology of the disease. We here report substitution of hydroxyl groups at C-6 alpha, C-7 beta and predominantly at C-7 alpha of [3H]5 alpha-androstane-3 beta,17 beta-diol on incubation of 3 and 8.5 nM substrate concentrations with minced and explanted human BPH tissue. Fibroblasts isolated from the same prostatectomy specimen hydroxylated 3 nM radiosubstrate mainly at C-6 alpha, with extensive metabolism to 17-oxosteroids. Epithelial cells from the same tissue source substituted to the same extent at the three positions. Competing 3 beta-hydroxysteroid dehydrogenase exceeded hydroxylase activity only in epithelial-cell cultures. Our findings support previous evidence that prostatic epithelial and stromal cells make different contributions to androgen disposition by the 3 beta-hydroxysteroid pathway. PMID- 2581070 TI - The antiarrhythmic actions of intravenous and oral UM424 in postinfarction canine myocardium. AB - The electrophysiologic and antiarrhythmic effects of oral and intravenous UM424 were studied in canine models of acute and chronic myocardial injury. In the first phase of this study, reentrant ventricular tachyarrhythmias and/or ventricular fibrillation were initiated by programmed electrical stimulation techniques in seven dogs 48-120 h after myocardial infarction. The cycle length of these reentrant ventricular beats was 176 +/- 16 ms, and they were accompanied by fractionated asynchronous epicardial electrical activity in the injured region that bridged the diastolic interval, i.e., 143 +/- 37 ms. When this prolonged, diastolic electrical activity ceased, the ventricular tachyarrhythmias ceased. UM424 5 mg/kg i.v. increased the effective refractory period of the normal myocardium by 21 ms (p less than 0.05), depressed cardiac conduction in the injured, infarcted myocardium and suppressed these reentrant tachyarrhythmias. Ventricular fibrillation could not be initiated after UM424. In the second phase of this study, a canine model of coronary artery thrombosis was used to produce spontaneous ventricular arrhythmias. UM424 60 mg/kg p.o. converted these ventricular arrhythmias to normal sinus rhythm. This pharmacologic action was not associated with deleterious hemodynamic side effects and lasted for 3 h, the duration of each experiment. These results demonstrate that after oral or intravenous administration, UM424 possess antiarrhythmic and antifibrillatory actions in canine models of acute and chronic myocardial injury. PMID- 2581071 TI - Effect of ketanserin on phenylephrine-dependent changes in splanchnic hemodynamics and systemic blood pressure in healthy subjects. AB - We studied the effect of ketanserin on basal status and phenylephrine-dependent changes in arterial blood pressure and splanchnic hemodynamics in seven healthy subjects. The drug was administered as an intravenous bolus of 10 mg followed by infusion of 4 mg/h. After a basal period of saline or ketanserin infusion, phenylephrine was infused at a constant rate in a fixed dose sequence of 1, 2, and 3 micrograms/kg/min. Blood pressure was measured intraarterially. Splanchnic blood flow, mean wedged hepatic blood pressure, and splanchnic vascular resistance were assessed by means of the hepatic venous catheter technique using indocyanine green dye. At steady-state plasma concentrations, basal arterial pressure and heart rate were not altered in this small group of normal subjects, whereas mean wedged hepatic venous pressure was lowered by ketanserin. During saline infusion, phenylephrine provoked a dose-dependent rise in arterial and wedged hepatic blood pressure; these effects were attenuated by ketanserin. Phenylephrine induced a significant, but not dose-dependent, decrease in estimated splanchnic blood flow. Ketanserin did not relevantly influence basal or phenylephrine-dependent splanchnic blood flow. We suggest that the hypotensive action of ketanserin is in part related to an interaction at alpha 1 adrenoceptors. Moreover, a dissociation of effects on vascular alpha-receptors seems to exist in the splanchnic and systemic circulations. PMID- 2581072 TI - Pharmacodynamic comparison of verapamil and nifedipine in anesthetized dogs. AB - The relationships between steady-state plasma concentrations of verapamil or nifedipine and the resultant hemodynamic and electrophysiologic effects were evaluated in anesthetized, instrumented dogs. In different groups of animals, the drugs were given intravenously by loading-maintenance infusions designed to rapidly achieve and sustain stable plasma drug concentrations, over four different target ranges which span those found in clinical use of these agents. Plasma levels of nifedipine varied from 5 to 125 ng/ml, and those of verapamil, from 40 to 500 ng/ml. Nifedipine produced no apparent effects on the surface electrocardiogram. Verapamil dosing resulted in progressive prolongation of the PR interval as plasma drug levels increased from 40 to 250 ng/ml; at higher drug levels, complete atrioventricular block occurred. At the highest plasma concentrations used, the maximal vasodilation produced by both drugs was approximately equal, with mean aortic pressure levels falling to 50-60% of control values. The effects of the two agents on cardiac pump performance, however, differed: nifedipine administration produced dose-related increases in cardiac output at all plasma drug concentrations studied; the effects of verapamil were critically dependent upon drug levels in plasma, with cardiac output increased above control values at drug concentrations between 40 and 250 ng/ml, and progressively depressed at higher plasma levels of the drug. As a result, the calculated systemic vascular resistance declined progressively during nifedipine administration, while after verapamil doses, this parameter varied inversely with observed effects on cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581073 TI - Left ventricular performance in spontaneously hypertensive rats after chronic beta 1-adrenoceptor blockade with atenolol. AB - We evaluated the role of chronic cardioselective beta-adrenoceptor blockade in left ventricular (LV) function in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Commencing at 4 weeks of age, the animals were injected twice daily (20 mg/kg) with atenolol and were studied at either 10 or 16 weeks of age, to compare the stages of developing and established hypertension in SHR. Both blood pressure and LV mass were attenuated in the treated SHR. Ventricular function-evaluated by increasing preload (infusion of Tyrode solution) and recording indices of peak cardiac output, i.e., cardiac index (CI), stroke index (SI), and acceleration of flow-was similar in SHR and WKY at both 10 and 16 weeks of age. At 10 weeks, peak CI and SI were not significantly different in treated and non-treated SHR. By 16 weeks, however, atenolol treatment was associated with a significant decrease in peak CI (20%) attributable mainly to a lower SI. LV end-diastolic and systolic pressures were not affected by chronic treatment with the beta-adrenoceptor antagonist. It is concluded that, when prolonged atenolol treatment is initiated during early postnatal life, peak LV function in SHR is compromised. PMID- 2581075 TI - Initial evaluation of transdermal timolol: serum concentrations and beta blockade. AB - The serum concentrations and beta-blockade after dermal application of timolol ointment were evaluated in six healthy men (21-31 years old; 74-82 kg). Two patches (25 cm2) containing placebo and either 30 (n = 2) or 60 mg (n = 4) timolol base were randomly applied to the chest for 30 h. Serial serum concentrations of timolol were measured by a radioligand receptor assay. Bicycle ergometry, at a predetermined workload, was performed before and at 3, 8, 24, and 48 h after patch application; mean +/- SD heart rates (beats/min) at these times were 167 +/- 2, 158 +/- 7, 125 +/- 7, 120 +/- 5, and 150 +/- 5 (last 3 values: p less than 0.05 from pretreatment), and beta-blockade was evident in all subjects. Measurable serum concentrations in the therapeutic range were achieved in all subjects. The change in exercise-induced heart rate (y) was closely related to log timolol serum concentration (x) (y = -36 X - 5.3; r = -0.92; p less than 0.001). Based on the amount of timolol in the residual ointment, 50-60% of the original timolol dosage was delivered from the patch. Skin irritation under the patch compared with placebo was minimal. Further studies are warranted to assess the potential clinical utility of transdermal timolol. PMID- 2581074 TI - Antiarrhythmic effects of flecainide against canine ventricular arrhythmias induced by two-stage coronary ligation and halothane-epinephrine. AB - We studied the electrophysiologic effects of flecainide on noninfarcted and infarcted dog hearts and in dogs anesthetized with halothane and administered intravenous epinephrine. Flecainide demonstrated no effect on atrial conduction times, but significantly (p less than 0.05) increased ventricular conduction times in noninfarcted, infarcted, and halothane-epinephrine-exposed dog hearts. Atrial and ventricular effective refractory periods (ERPs) were significantly (p less than 0.05) increased by flecainide. The increase in ERP was more pronounced in infarcted than in noninfarcted dog hearts. Flecainide significantly (p less than 0.05) decreased the echo zone for two or more repetitive ventricular responses in infarcted dog hearts and eliminated all ventricular arrhythmias observed at 48 h after coronary artery ligation. The dose of epinephrine required to induce ventricular arrhythmias in dogs anesthetized with halothane was significantly increased (p less than 0.05) by flecainide. Acute intravenous administration of flecainide to dogs with infarcted hearts produced sinus arrest, transient third-degree heart block, inability to pace, right bundle branch block, and torsade des pointes. Our results provide evidence that flecainide produces its antiarrhythmic effects by increased ventricular ERP and ventricular conduction time. Caution is advised when administering flecainide to patients with previous history of myocardial infarction. PMID- 2581077 TI - Mechanisms of age-related differences in the cardiotoxic action of digitalis. AB - Age-associated ouabain sensitivity was investigated in isolated perfused guinea pig heart and the findings were correlated with its receptor function. Ouabain (0.1 mumol L-1) produced average positive inotropic responses of 22% in 15-day old, 25% in 4-6 month-old, and 34% in 18-24-month-old guinea pig hearts. The time required to produce the greatest positive inotropic response was 28 min in 15-day to 6-month-old guinea pig hearts and 20 min in 18-24-month-old guinea pig hearts. To cause arrhythmias and cardiac arrest, 2.1 mumol L-1 ouabain was required in age groups of 15 days to 6 months, and 1.2 mumol L-1 in age groups of 12-24 months. The time of onset of arrhythmias and cardiac arrest was also significantly less in older than in younger animals. Cardiac membranes from 12-24 month-old guinea pig hearts had significantly lower Na+, K+ -ATPase activity per mg of sarcolemmal protein and numbers of [3H]ouabain binding sites than those from 28-day- to 6-month-old hearts. The enzyme inhibition by 0.1 mumol L-1 ouabain was, however, less in younger than in older groups. The difference in the inhibition of enzyme was reflected in lower ouabain binding affinity (Kd) in younger animals. The data confirm the existence of an age-related difference in ouabain sensitivity and suggest that these differences may be due to changes in receptor function. PMID- 2581076 TI - Dual effect of adrenaline on noradrenaline release in the pithed rabbit. AB - We examined the effects of adrenaline on the noradrenaline release rate and plasma catecholamine levels in the pithed rabbit with electrically stimulated sympathetic outflow (3 Hz). Adrenaline (0.06 micrograms/kg/min) increased the rate of noradrenaline release into the plasma. This increase was prevented by propranolol (0.2 mg/kg + 0.1 mg/kg/h) and probably involves activation of presynaptic beta-adrenoceptors. A higher dose of adrenaline (1.0 micrograms/kg/min) significantly reduced the noradrenaline release rate. The reduction was "reversed" to a facilitatory effect by phenoxybenzamine (4 mg/kg). Propranolol alone slightly inhibited the noradrenaline release rate. After pretreatment with desipramine (1.0 mg/kg + 0.2 mg/kg/h), the inhibitory effect of propranolol on noradrenaline release was more pronounced and blood pressure was also lowered. However, in rabbits pretreated with captopril (1 mg/kg) in addition to desipramine, the sympathoinhibitory effect of propranolol was not observed. These results suggest that adrenaline can activate either presynaptic beta adrenoceptors to increase noradrenaline release or, in higher doses, presynaptic alpha-adrenoceptors to inhibit noradrenaline release in vivo. The decrease in the noradrenaline release rate produced by propranolol alone may not be due to blockade of facilitatory presynaptic beta-adrenoceptors, but rather to depression of renin secretion. This would decrease angiotensin II formation and hence decrease the presynaptic release-enhancing effect of angiotensin II. PMID- 2581078 TI - Inhibition of platelet aggregation by oral digoxin and reversal with nifedipine. AB - To study the effect of cardiac glycosides on platelet function, we obtained serial blood samples from 18 normal male volunteers before and 3, 5, and 7 weeks after beginning digoxin therapy (0.375 mg daily). The combined effect of digoxin and nifedipine (mean dose, 57 mg/day) was assessed during the 5th week. Spontaneous platelet aggregation and platelet response to adenosine diphosphate (ADP) were measured in whole blood by electronic particle sizing. Digoxin (mean serum concentration, 0.9 ng/ml) caused significant reduction in total volume and mean size of platelet aggregates formed in response to ADP. However, with addition of nifedipine, the volume and mean size of aggregates returned to baseline measurements. In vitro administration of digoxin to whole blood failed to inhibit ADP-induced platelet aggregation. The volume of spontaneously induced aggregates decreased with digoxin; however, the decrease was not statistically significant. These data indicate that digoxin given in vivo for several weeks inhibits platelet response to ADP; this effect is reversed by the addition of nifedipine. PMID- 2581079 TI - Amrinone and energy output of rabbit papillary muscles. AB - We studied the effects of amrinone (300 micrograms X ml-1) on the mechanical and energetic outputs of nonfailing rabbit papillary muscles at 27 degrees C using a myothermic technique. Amrinone was found to markedly stimulate the basal (i.e., nonbeating) metabolism. In mechanical experiments, at a 0.5-Hz stimulus rate, amrinone increased the rate of stress development and peak active stress but shortened the time to peak stress and the contractile duration. The linear relationship between total (active + passive) stress and heat production was altered by amrinone such that there was a 68% increase in the activation heat component (intercept) and an 11% increase in the energy cost per unit stress development (slope). In afterloaded isotonic experiments amrinone increased the capacity of papillary muscles to accomplish external work (W) by approximately 50% on average; however, this effect was associated with an increased total energy usage per beat (ET) such that the overall mechanical efficiency (W/ET X 100%) was not significantly altered at any load level. We conclude that amrinone greatly increases calcium delivery to the myofilaments and slightly increases the cost of stress development. These effects are examined in the light of amrinone's postulated mode of action, and possible reasons for the clinical observation of a decrease in myocardial oxygen consumption after amrinone administration are considered. PMID- 2581080 TI - Effects of the acylcarnitine-transferase blocking agent sodium 2[5-(4 chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) on metabolism and regional function in the underperfused canine myocardium. AB - We investigated the effects of sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2 carboxylate (POCA) on regional myocardial function and metabolism in anesthetized, thoracotomized dogs subjected to a 53.5% reduction in flow through the circumflex branch of the left coronary artery (LCX). Regional function in the area supplied by the LCX and the left anterior descending coronary artery (LAD) was assessed by means of two pairs of subendocardially inserted ultrasonic transducers. Hemoglobin content, oxygen saturation, pH, PCO2, PO2, lactate, glucose, and free fatty acids were determined in arterial and local venous blood obtained from the area supplied by the LCX. POCA (20 mg/kg/20 min i.v.) induced a transient decrease in left ventricular power and cardiac output. Arterial free fatty acid (FFA) levels increased continuously throughout the experiment, whilst arterial glucose levels showed a continuous decrease. FFA uptake, lactate release, and oxygen uptake were reduced in the underperfused area by POCA. At the same time, POCA induced a transient increase in end-diastolic segment length and a sustained decrease in systolic shortening during the ejection phase in the underperfused area. No changes in regional function were observed in the area perfused by the nonconstricted LAD. PMID- 2581081 TI - Systemic and pulmonary hemodynamic effects of indapamide in patients with mild arterial hypertension. AB - We studied the hemodynamic mechanism responsible for the antihypertensive effect of indapamide in eight patients with mild essential hypertension. Systemic and pulmonary hemodynamics were measured using direct techniques (right heart catheterization and thermodilution method), before and 7-10 days after oral treatment with indapamide (2.5 mg/day). Indapamide reduced mean arterial blood pressure from 120 +/- 1.6 (mean +/- SE) to 101 +/- 1.4 mm Hg (p less than 0.01), and mean pulmonary artery pressure from 21 +/- 0.59 to 17 +/- 1.05 mm Hg (p less than 0.01). Total peripheral vascular resistance (TPR) and pulmonary vascular resistance were reduced from 36 +/- 0.85 to 29 +/- 0.72 U/m2 (p less than 0.01) and from 4.3 +/- 0.17 to 3.8 +/- 0.18 U/m2 (p less than 0.01), respectively. Indapamide did not change cardiac index (CI) (3,311 +/- 61.6 vs. 3,325 +/- 72.1 ml/min/m2), heart rate (HR) (75 +/- 1.7 vs. 75 +/- 9 beats/min), mean rate of left ventricular ejection index 140 +/- 2.04 vs. 139 +/- 1.99 ml/s/m2, and stroke index (44 +/- 5.6 vs. 43 +/- 5.8 ml/m2). Mean pulmonary wedge pressure decreased from 7 +/- 0.6 to 5 +/- 0.5 mm Hg (p less than 0.05). Body weight, 24-h urinary volume, and hematocrit were unchanged after treatment. We conclude that the hemodynamic mechanism responsible for the antihypertensive action of indapamide is a reduction in TPR without changes in CI and HR. PMID- 2581082 TI - Acute hemodynamic effects of intravenous amiodarone in patients with coronary artery disease. AB - The acute hemodynamic effects of intravenous amiodarone (Cordarone injectable; Labaz) were studied during cardiac catheterization in 16 male patients with coronary artery disease (age range, 38-64 years; mean, 53 years). Amiodarone was administered as a bolus at a dosage of 5 mg/kg bodyweight over a 1-min period. Measurements were made 5, 10, and 15 min thereafter. The drug had little effect on heart rate, aortic pressure, cardiac index, and vascular resistances. There were small and nonsignificant increases in left ventricular end-diastolic pressure and end-diastolic volume. The ejection fraction decreased slightly and not significantly. In addition to some increases in pulmonary wedge, pulmonary artery, and right atrial pressures, the significant findings were a 15% decrease in maximal dP/dt and a 12% decrease in left ventricular work. These changes point to a slight negative inotropic effect of amiodarone. PMID- 2581083 TI - Changes in cardiac function following administration of thyroid hormones in thyroidectomised rats: assessment using the isolated working rat heart preparation. AB - We investigated the changes in cardiac function following alterations in thyroid state of rats, using the isolated working heart preparation. This technique allows heart rate, contractility, and pump function to be studied under controlled conditions. Surgical thyroidectomy resulted in significant impairment of cardiac function. Single doses of 3,5,3'-triiodo-L-thyronine (T3) or L thyroxine (T4) were given to thyroidectomised rats. Cardiac function was restored to normal within 48 h of administration of 0.5 mg/kg T3 or 2.5 mg/kg T4 without significant changes in heart weight. The dose-response relationships between T3 and T4 and cardiac function showed that significant changes occurred after single doses of T3, 0.02 mg/kg, or T4, 0.5 mg/kg. An increase in contractility was seen within 12 h of administration of T3, before other physiological effects of T3 are reported to occur. This indicates that the change in contractility is the result of a direct effect of thyroid hormones on the heart and is not secondary to changed loading conditions of the heart. Changes in heart rate occurred between 18 and 48 h. The maximum heart rate achieved did not exceed that in hearts from euthyroid rats, although contractility could be increased above euthyroid levels. PMID- 2581084 TI - Cardiac actions of phencyclidine in isolated guinea pig and rat heart: possible involvement of slow channels. AB - The mechanisms responsible for the positive inotropic effect of phencyclidine were studied in isolated preparations of guinea pig and rat heart. In electrically paced left atrial muscle preparations, phencyclidine increased the force of contraction; rat heart muscle preparations were more sensitive than guinea pig heart muscle preparations. The positive inotropic effect of phencyclidine was not significantly reduced by a combination of phentolamine and nadolol; however, the effect was competitively blocked by verapamil in the presence of phentolamine and nadolol. Inhibition of the outward K+ current by tetraethylammonium chloride also produced a positive inotropic effect; however, the effect of tetraethylammonium was reduced by phentolamine and nadolol, and was almost insensitive to verapamil. The inotropic effect of phencyclidine was associated with a marked prolongation of the action potential duration and a decrease in maximal upstroke velocity of the action potential, with no change in the resting membrane potential. In partially depolarized atrial muscle preparations, which were reactivated by elevation of the extracellular Ca2+ level and stimulation at a high voltage, phencyclidine markedly increased the amplitude and the duration of the slow action potentials. Rat heart muscle preparations had higher sensitivity to these effects of phencyclidine. The specific [3H]phencyclidine binding observed with membrane preparations from guinea pig ventricular muscle was saturable with a single class of high-affinity binding site. This binding was inhibited by verapamil, diltiazem, or nitrendipine, but not by ryanodine or tetrodotoxin. These results suggest that the positive inotropic effect of phencyclidine results from enhanced Ca2+ influx via slow channels, either by stimulation of the channels or secondary to inhibition of outward K+ currents. PMID- 2581085 TI - Inotropic and chronotropic activity of berberine on isolated guinea pig atria. AB - The cardiac effects of berberine were studied in isolated right and left atrial preparations from guinea pigs. In spontaneously beating right atria, berberine (1 X 10(-5) -3 X 10(-4) M) caused bradycardia, which was not prevented by atropine (1 X 10(-7) M). Over the same concentration range, berberine increased developed force (dF) in left atria electrically driven at 1.5 Hz. This occurred in both untreated and reserpine-treated tissues as well as in the presence of 5 X 10(-7) M propranolol and 1 X 10(-5) M phentolamine. At a stimulation frequency of 1.5 Hz, left atrial responses to each concentration of berberine reached steady state in approximately 10 min. Concentrations of berberine greater than 3 X 10(-4) M depressed dF and increased resting tone until eventually the left atria failed to contract. Analysis of the effects of berberine on the contractile waveform of left atria showed a concentration-dependent increase in maximal positive dF/dt, maximal negative dF/dt, time to peak tension, and relaxation time. When maximal negative dF/dt was normalized for changes in dF (-dF/dt/dF), berberine showed inhibition of the relaxation process. Berberine had only slight effects on post rest potentiation and paired pulse stimulation, but enhanced the response of left atria to increases in stimulation frequency. From these results, it appears that berberine has a unique profile of action in isolated guinea pig atrial tissue, showing both positive inotropic and negative chronotropic activity. Berberine produces its positive inotropic effect by enhancing both the force-velocity relationship and the duration of the active state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581086 TI - Analysis of the positive inotropic effect of ibopamine in the blood-perfused canine papillary muscle. AB - The positive inotropic effect of ibopamine, an orally active dopamine analogue, was examined in an isolated canine papillary muscle perfused with blood of a donor dog through the anterior septal artery (ASA). Administered intraduodenally (25 mg/kg) in the donor dog, ibopamine increased the left ventricular dP/dtmax as well as the contractile force of the isolated papillary muscle. Injected into the ASA (10 micrograms) it had only a slight positive inotropic effect, which was greatly enhanced by preincubation of the drug in plasma. Addition of physostigmine to the plasma prevented this enhancement. Propranolol (0.2 mg/kg i.v.) shifted the dose-response curves for the positive inotropic effect of plasma-dissolved (PD) ibopamine (0.3-10 micrograms), norepinephrine (NE; 1-100 ng), and deoxyepinephrine (Epinine; 0.3-10 micrograms) to the right. At 3 micrograms/min cocaine enhanced the response to NE, but enhanced only slightly the responses to Epinine and PD ibopamine; at 10 micrograms/ml it enhanced the response to NE, but depressed slightly the responses to Epinine and PD ibopamine. The positive inotropic effect of intraduodenally administered ibopamine may be caused by active metabolite(s), possibly epinine, from its hydrolysis by esterases, and may be mediated by both direct and indirect stimulation of beta adrenoceptors in the canine heart. PMID- 2581087 TI - Cardiovascular responses to central clonidine, alpha-methyldopa, and 6 hydroxydopamine in conscious normotensive and spontaneously hypertensive rats following naloxone. AB - The possible involvement of endogenous opioid peptides in the cardiovascular responses observed following central alpha-adrenoceptor stimulation with clonidine, alpha-methyldopa (alpha-MD), and 6-hydroxydopamine (6-OHDA) was examined in conscious normotensive Wistar and spontaneously hypertensive (SHR) rats. Clonidine [2.5 micrograms intracisternally (i.c.)] produced rapid hypotension (-36 +/- 2 mm Hg) and bradycardia (-53 +/- 5 beats/min) in SHR that were similar to observations in animals given either naloxone (50 micrograms i.c. or 10 mg/kg i.p.) or appropriate saline control injections. Peripheral doses of naloxone (1-2 mg/kg) or saline did not further change arterial pressure or heart rate in either Wistar rats or SHR given alpha-MD (1.0 mg i.c.) 3 h earlier. In addition, central doses of naloxone (3 X 50 micrograms i.c.) given at hourly intervals did not affect the responses to alpha-MD. Central administration of 6 OHDA acutely releases noradrenaline which produces an initial fall in arterial blood pressure and heart rate. Intracisternal 6-OHDA (400 micrograms) produced similar time course and maximum circulatory effects in rats given naloxone (50 micrograms i.c. before and at each subsequent hour) as in saline-treated animals. Naloxone (1 mg/kg s.c.) significantly attenuated morphine-induced analgesia. These findings do not support a critical role of endogenous opioids in mediating the acute antihypertensive actions of clonidine and alpha-MD or in the cardiovascular responses produced by noradrenaline release following central 6 OHDA. PMID- 2581088 TI - Relationships between the severity of myocardial ischaemia, reperfusion-induced ventricular fibrillation, and the late administration of dazmegrel or nifedipine. AB - We examined the effects of late administration of the thromboxane synthetase inhibitor dazmegrel (UK 38485) and the calcium channel blocker nifedipine in anaesthetised greyhounds subject to occlusion of the left anterior descending coronary artery with reperfusion after 40 min of ischaemia. Administration of dazmegrel, 3 mg/kg i.v., or nifedipine, 5 micrograms/kg + 1 microgram kg-1 min-1 i.v., 25 min after coronary artery occlusion failed to reduce the incidence of reperfusion-induced ventricular fibrillation (controls, 70%; dazmegrel, 50%; nifedipine, 70%; n = 10). Measurement of plasma prostanoid concentrations indicated that within 5 min of receiving dazmegrel there was a significant reduction in thromboxane B2 concentrations in the local coronary vein draining the ischaemic myocardium. The results suggest that the occurrence of reperfusion induced ventricular fibrillation depends upon the severity of changes occurring during ischaemia. Analysis of various factors suggested that the number of ischaemia-induced arrhythmias, heart rate, and the magnitude of changes in local coronary venous PO2 may be important predictors of reperfusion-induced ventricular fibrillation. PMID- 2581089 TI - Thyrotropin-releasing hormone blocks the hypotensive effects of platelet activating factor in the unanesthetized guinea pig. AB - Platelet-activating factor (PAF) and leukotrienes, newly described classes of vasoactive lipids, may play a role in anaphylaxis. It has recently been suggested that the vasoconstrictor effects of PAF in isolated rat lung are related to release of leukotrienes C4 and D4. Thyrotropin-releasing hormone (TRH), a tripeptide, has potent antihypotensive activity in experimental shock, including that resulting from either leukotriene D4 administration or antigen-induced anaphylaxis. We utilized an unanesthetized guinea pig model to study the relationships among PAF, leukotrienes, and TRH and their potential interactions on the cardiovascular system. PAF (1 nmol/600 g body weight i.v.) produced profound hypotension which was completely blocked by TRH (2 mg/kg i.v.). Nafazatrom or FPL 55712, a presumed receptor antagonist of leukotrienes, was ineffective, whereas U-60257, a leukotriene synthesis inhibitor, displayed incomplete blockade. Moreover, leukotriene-like immunoreactivity in plasma did not increase following PAF administration. Thus, hypotension produced by PAF does not appear to result secondarily from release of cysteinyl leukotrienes. Moreover, the ability of TRH to block the hypotensive effects of PAF may partially account for its beneficial effects in experimental anaphylaxis and provides further rationale for the therapeutic evaluation of this peptide in anaphylactic shock. PMID- 2581090 TI - The effects of milrinone on action potential characteristics, conduction, automaticity, and reflected reentry in isolated myocardial fibers. AB - Milrinone, a newly developed analogue of amrinone, possesses potent positive inotropic effects. Electrophysiologic actions of the drug have thus far been reported in only one study conducted on canine Purkinje fibers. The present study used microelectrode techniques to evaluate the electrophysiologic effects of milrinone on normal and depressed isolated ventricular myocardial fibers. At apparent therapeutic concentrations (0.1-0.2 microgram/ml), milrinone abbreviated action potential duration and refractory period in normal myocardial fibers, but caused no significant changes in any other parameter. At similar concentrations, the drug markedly altered the electrical activity of K+-depolarized preparations, producing an increase in action potential amplitude, duration, and dV/dtmax. Milrinone also restored regenerative activity in K+-inactivated ventricular fibers. The drug exerted important effects on conduction velocity, refractoriness, and reflected reentry generated in fibers mounted in a three compartment chamber in which the central segment was depressed with an "ischemic" solution. Depending on the initial level of block, the drug concentration, and the segments of the preparation exposed to the drug, milrinone (a) suppressed the arrhythmia, (b) shifted its frequency dependence, or (c) induced reentry. Similar results were obtained in homogeneously depressed fibers. The drug produced no major changes in depolarization-induced automaticity. Thus, in addition to its inotropic actions, milrinone produces important electrophysiologic effects. By restoring or improving conduction through areas of depressed conductivity, the drug may alter the manifestation of arrhythmias. PMID- 2581091 TI - Are the sympathetic neural effects of digoxin and quinidine involved in their action on cardiac rhythm? AB - This study was initiated to determine if ventricular arrhythmia induced by digoxin was associated with a nonuniform neural discharge in the cardiac sympathetic postganglionic fibers. In addition, splanchnic neural discharge was monitored to explore the role of adrenal medullary catecholamines in digoxin induced arrhythmia. Experiments were performed to ascertain whether the antiarrhythmic effects of quinidine in digoxin-induced arrhythmias were related to an action on cardiac sympathetic neural discharge induced by digoxin. All cats were anesthetized with alpha-chloralose and given atropine; some were pretreated with quinidine (10 or 20 mg/kg i.v. 15 min before digoxin). Digoxin was given every 15 min until death; the first three doses were 50 micrograms/kg i.v., and all subsequent doses were 25 micrograms/kg. The mean +/- SE time to arrhythmia was 32 +/- 4 min (n = 16) and was significantly increased only after 20 mg/kg quinidine (64 +/- 7 min; p less than 0.001). Mean +/- SE time to death was also increased from 74 +/- 4 to 98 +/- 7 min (p less than 0.001). Postganglionic cardiac sympathetic neural discharge before digoxin-induced arrhythmia was depressed. Of the 28 nerves monitored in 16 animals receiving digoxin, in the minute before development of arrhythmia, 22 nerves were depressed, 3 were increased, and 3 showed no change when compared with the predigoxin control. Following this depression of neural discharge, arrhythmia developed, and the neural discharge began to rise, eventually increasing above control levels. During this time the variability of the neural discharge increased greatly, as evidenced by large SE values, so that the mean values were not significantly different from control levels. Splanchnic neural discharge (n = 9) progressively decreased, reaching 66% of control values after the third injection of digoxin; the discharge then began to increase gradually toward control levels in the next 10 min and arrhythmia developed. The data indicate that the arrhythmias caused by digoxin are not associated with the development of nonuniform discharge patterns in the cardiac sympathetic nerves. Furthermore, action on the splanchnic nerve discharge is not involved in the arrhythmogenic effects of digoxin. Pretreatment with quinidine, 20 mg/kg, decreased both splanchnic and post-ganglionic cardiac sympathetic neural discharge, arterial blood pressure, and heart rate. Although quinidine, 20 mg/kg, increased the time to arrhythmia induced by digoxin, the depression of postganglionic cardiac or splanchnic neural discharge did not seem to be a major component of the antiarrhythmic effect of quinidine. PMID- 2581093 TI - Combined effects of ouabain and hypoxia on the transmembrane potential of of canine cardiac Purkinje fibers. AB - The effects of hypoxia on the transmembrane potential of dog Purkinje cells in isolated, superfused fiber bundles pretreated with ouabain were studied. Cells stimulated electrically at 93/min were exposed to ouabain, 2.1 X 10(-7) M, until the magnitude of phase 4 depolarization increased to 7-12 mV. Arrhythmias did not occur. Following a 10-min washout period, hypoxic solution (PO2 = 15-50 mm Hg) was applied for 2-5 min. This caused decreases in maximum diastolic potential, overshoot, rising velocity of phase 0, and duration of the action potential. The slope of depolarization during phase 4 increased markedly. Arrhythmias characterized by escape rhythms or single and multiple bursts of premature excitations occurred in greater than 90% of the experiments. None of these changes was noted when identical levels of hypoxia were applied for a similar period to normal cells. Blockade of the beta-adrenergic receptors with propranolol, 0.3 mg/L, did not alter the response of ouabain-pretreated cells to hypoxia in any manner, ruling out release of endogenous catecholamines as essential for the observed effects. These results suggest that ouabain and hypoxia have a synergistic effect directly on the cells and produce the observed changes in membrane potential. The ventricular arrhythmias observed in digitalized humans or animals that become hypoxemic may result either from the induction of oscillatory after potentials in Purkinje cells causing triggered spontaneous excitations or from reentry of excitation. PMID- 2581092 TI - Effects of nisoldipine, a new calcium antagonist, on myocardial infarct size and cardiac dynamics following acute myocardial infarction. AB - While some calcium antagonists are effective in reducing myocardial infarct size, this beneficial effect may be accompanied by negative inotropic effects. In the following study, a new dihydropyridine calcium antagonist, nisoldipine, was assessed for its effect on infarct size, hemodynamics, and regional function as assessed by percent systolic wall thickening of the left ventricle (SWT) by 2D echocardiography. Open-chest, anesthetized dogs were subjected to 6 h of coronary artery occlusion. After 10 min of coronary artery occlusion, the ischemic area at risk of infarction (AR; % of left ventricle) was determined by left atrial injection of 99mTc-labeled albumin microspheres with subsequent postmortem autoradiography. After 6 h, the hearts were excised, and the area of necrosis (AN) determined by incubation of left ventricular slices in triphenyltetrazolium chloride stain. Treated dogs received 0.005 mg/kg nisoldipine by intravenous infusion at 1.91 ml/min (lasting approximately 8.7 min) during three dosing periods: 15 min, 2 h, and 4 h postocclusion. The AR of eight controls (25.7 +/- 1.8%) was not significantly different from that of 11 treated dogs (25.1 +/- 1.9%). However, the AN/AR X 100 of treated dogs was significantly less than that of controls (62.8 +/- 9.3 vs. 91.6 +/- 7.0%; p less than 0.05). Mean arterial pressure fell in treated dogs by 15.7% (p less than 0.01) at 15 min and by 5.7% (p less than 0.05) at 4 h but not at 2 h postocclusion. Heart rate was not affected by nisoldipine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581094 TI - Effects of a novel calcium channel agonist dihydropyridine analogue, Bay k 8644, on pig coronary artery: biphasic mechanical response and paradoxical potentiation of contraction by diltiazem and nimodipine. AB - Bay k 8644 is a structural analogue of the 1,4-dihydropyridines whose pharmacological actions on heart and vascular smooth muscle are opposite from those of nifedipine and other similar calcium antagonists. We have examined the action of Bay k 8644 ("calcium channel agonist") on isolated porcine coronary artery rings. The interactions between Bay k 8644 and the vasodilators isosorbide dinitrate (ISDN), diltiazem, and nimodipine were quantitated. Bay k 8644 produced a biphasic, dose-dependent mechanical response, with contraction occurring over the concentration range of 1-350 nM (ED50 = 11.4 nM) and relaxation observed at concentrations greater than 350 nM (IC50 = 5.7 microM). ISDN, diltiazem, and nimodipine relaxed, in a dose-dependent manner, maximal Bay k 8644-induced contractions. When the coronary rings were pretreated for 25-90 min with 80% inhibitory concentrations of these vasodilators, there was little or no effect by ISDN on Bay k 8644-induced contractions; however, there was a surprising potentiation by diltiazem and by nimodipine. Pretreatment of coronary rings with higher concentrations of ISDN or diltiazem caused an inhibition of Bay k 8644 induced contraction, while pretreatment with higher concentrations of nimodipine caused further potentiation of contraction elicited by Bay k 8644. Bay k 8644 increased the tension developed in response to high potassium (potential-operated channel activation) or histamine (receptor-operated channel activation). To account for the biphasic response to Bay k 8644 (dose-dependent contraction and relaxation), and the unexpected potentiation of Bay k 8644-induced contraction by nimodipine and by diltiazem, a molecular model is proposed for vascular smooth muscle in which Bay k 8644 functions as a partial calcium channel agonist at two functionally distinct 1,4-dihydropyridine "receptor sites." PMID- 2581095 TI - Disopyramide and quinidine bind with inverse selectivity to muscarinic receptors in cardiac and extracardiac rat tissues. AB - We investigated the interactions of disopyramide and quinidine with the muscarinic receptor in tissue homogenates from rat atrium, ventricle, cortex, submandibular gland, and urinary bladder by means of competition binding experiments, using the tritium-labeled antagonist N-methyl-4-piperidyl benzilate. The drugs displayed heterogeneous characteristics of binding to the muscarinic receptors in the different tissues. The binding affinity of quinidine to the muscarinic receptor in atrial tissue was five to 10 times greater than in the other tissues studied, whereas the affinity of disopyramide to the muscarinic receptor in the heart was five times lower than in the other tissues. This inverse selectivity shown by the two drugs in their binding to cardiac and to noncardiac tissues may explain the extracardiac antimuscarinic side effects of treatment with disopyramide and their absence with quinidine. PMID- 2581097 TI - Alpha 1- and alpha 2-adrenoceptor-mediated pressor responses: are they differentiated by calcium antagonists or by functional antagonism? AB - We investigated the effect of cardiovascular depression on the pressor responses to the alpha 1-adrenoceptor selective agonist methoxamine, and the alpha 2 adrenoceptor selective agonist B-HT 920 in anesthetized ganglion-blocked rats. The calcium channel blocking drug nifedipine preferentially inhibited the effect of B-HT 920, as has been reported by other authors. Lowering the starting blood pressure by hemorrhage, by nitroprusside infusion, or by additional pentobarbitone also preferentially inhibited the pressor effect of B-HT 920. These selective effects of vascular depression on B-HT 920 are consistent with predicted interactions between functional antagonists and a partial (low efficacy) agonist. This was tested in part by reducing the maximum effect of methoxamine by phenoxybenzamine treatment. Under these conditions, methoxamine behaved like B-HT 920 in that it was sensitive to inhibition by nitroprusside infusion. By analogy, the vasodepressive effect of calcium channel blocking drugs could be responsible for the preferential inhibition of the vasoconstrictor responses to alpha 2-adrenoceptor agonists. It is concluded that a differential reliance on influx of extracellular Ca2+ by alpha 1- and alpha 2-adrenoceptors may not be the only explanation of the selective effect of calcium channel blocking drugs. PMID- 2581098 TI - Comparative pharmacokinetics of intravenous propranolol in black and white volunteers. PMID- 2581096 TI - Alterations in myocardial uptake of glutamate and release of alanine after propranolol, nifedipine, and glyceryl trinitrate in coronary artery disease. AB - We examined the effects of antianginal drugs on myocardial uptake of glutamate and release of alanine in patients with chronic effort angina. Thirty-three patients underwent two periods of atrial pacing, the second preceded either by no medication (controls) (n = 8), 0.1 mg/kg i.v. propranolol (n = 8), 30 mg nifedipine sublingually (n = 9) or 0.75 mg glyceryl trinitrate sublingually (n = 8). Before, during, and after each pacing period, coronary sinus blood flow (CSBF), oxygen uptake, and arteriocoronary sinus differences (ACs) of plasma glutamate and alanine were determined. In all groups of patients, arterial alanine concentration fell during the second test. Except for this fall, no metabolic change was seen in controls. Propranolol increased circulating arterial concentration and ACs values of glutamate throughout the test. Nifedipine did not change arterial glutamate concentration but decreased ACs glutamate before and after pacing. Glyceryl trinitrate decreased CSBF, oxygen uptake, and net myocardial uptake of glutamate before pacing despite unchanged arterial level and ACs values. Alterations of myocardial glutamate uptake after drugs may reflect metabolic effects of propranolol primarily exerted on extracardial sites and of nifedipine exerted on the myocardium itself, whereas changes after glyceryl trinitrate seem to be secondary to its cardiac unloading effect. Alterations in myocardial release of alanine were too small and inconsistent to be taken as drug effects. PMID- 2581101 TI - The measurement of changes in intracellular free calcium during action potentials in mammalian neurones. AB - This report describes the techniques we have developed to record changes in intracellular calcium concentration which take place during action potentials in the cell body of rat dorsal root ganglion neurones in vitro. The photoprotein, aequorin, was microinjected into the cell body of individual sensory neurones and light output from Ca2+-activated aequorin molecules was recorded with a photomultiplier tube attached to a modified inverted microscope. Aspects of the technology outlined here include: cell culture methods; a flow chamber for electrophysiological experiments on cell culture preparations; modifications to our inverted microscope; use of 150 mM KCl-filled microelectrodes; and an electronic device for processing the photomultiplier output. Some preliminary results are presented. PMID- 2581100 TI - Stability of immunocytochemical reactivity of neuronal substances following delayed fixation. AB - The rates of deterioration of immunocytochemical staining for 4 peptide and 2 neuronal antigens were studied on human, guinea pig and rat colon and urinary bladder. It was found that if the fixation started within 10 h after surgery or death, little change was seen in the pattern and intensity of the immunostains. When fixation was further delayed, the immunostaining gradually deteriorated in quality and decreased in quantity until, when fixation was delayed for 60-72 h, most of the original immunostaining was absent. The deterioration rates of the neuronal antigens in the urinary bladder were slower than in the colon and all antigens were preserved for longer at 4 degrees C than at 20 degrees C. The deterioration curves produced from the present findings provide a standard for comparison with the immunostaining results obtained on tissues where fixation is delayed. PMID- 2581102 TI - Some neurobiological applications of the BBC Model B microcomputer and Unilab 8 bit interface. AB - Four computer programs written for the BBC Model B microcomputer (coupled to a Unilab 8-bit interface) are discussed. These programs enable the system to be used as (1) a transient recorder, (2) a rapid signal averager, (3) a spike-train analyser and (4) an instrument for measuring the amplitude of single channel currents. Flow-charts illustrating the operation of each program are given along with a detailed discussion of how the programs may be used in the laboratory. The discussion is illustrated using recordings taken from experiments conducted on a range of neurobiological preparations. PMID- 2581099 TI - A prospective randomized study of hydroxyethyl starch, albumin, and lactated Ringer's solution as priming fluid for cardiopulmonary bypass. AB - The ideal priming fluid for cardiopulmonary bypass is not known. We designed a study to determine whether there are important differences in the clinical effects of hydroxyethyl starch versus albumin when used in priming fluid, and in the clinical effects of colloid versus crystalloid priming fluid. We prospectively randomized 83 adult patients undergoing coronary artery bypass or valve replacement. All patients were managed by standardized protocol, and they received one of three priming fluids for bypass: hydroxyethyl starch (HES), 26 patients; albumin (ALB), 28 patients, and lactated Ringer's solution (LRS), 29 patients. The groups were stratified by body weight and type of operation. We measured 41 variables relating to operative time factors, fluid balance, bleeding, and organ function (renal, cardiac, and pulmonary) at several time intervals. The LRS group had a significantly lower colloid osmotic pressure than the other two groups, and the HES group had a substantially higher blood viscosity. Although the prothrombin time was significantly lower in the LRS group (p less than 0.05), the differences were very small and not clinically important. The platelet count in the HES group was significantly lower than in the other two groups immediately after bypass, but it was not different by the time the patients left the operating room. There were no differences among the groups in chest tube drainage, blood bank usage, or fluid balance. Postoperatively, the pulmonary shunt fraction was significantly greater in the LRS group. Body weight increased more in the LRS than in the HES and ALB groups (p = 0.01). No adverse reaction to the prime solutions was noted. The differences between the HES and ALB groups--prothrombin time, platelet count, and blood viscosity--had no apparent clinical effects; thus, the two may be considered clinically equivalent. The greater somatic and pulmonary fluid accumulation in the LRS group suggests that colloid is preferable to crystalloid in priming fluid. PMID- 2581103 TI - [Continuing education in surgical nursing of adult patients]. PMID- 2581104 TI - A comparison of DNA repair synthesis in primary hepatocytes from young and old rats. AB - DNA repair synthesis has been compared in primary hepatocyte cultures obtained from 3-month-old and 16-20-month-old rats. Several morphological and metabolic characteristics were determined to assure cultures of comparable quality. DNA damage was induced by the addition of bleomycin or the exposure of the culture to UV irradiation. DNA repair (unscheduled DNA synthesis) was determined by measuring [3H]thymidine incorporation. After UV irradiation, there was almost twice as much [3H]thymidine incorporation in cells obtained from young rats as in those obtained from old rats. Equal amounts of bleomycin resulted in substantially greater damage to DNA in cells from old rats than from young rats. For equal amounts of DNA damage there was again diminished [3H]thymidine incorporation in cells obtained from old rats. Finally equal amounts of bleomycin resulted in equal damage to DNA when the bleomycin was added to isolated rat liver nuclei from young or old rats. Bleomycin treated nuclei from young rats incorporated substantially more [3H]thymidine triphosphate (TTP) than bleomycin treated nuclei from old rats. The results indicate that hepatocytes from old rats are much more susceptible to bleomycin than hepatocytes from young rats and that the capacity for DNA repair synthesis is impaired in hepatocytes from old rats. PMID- 2581105 TI - [Initial experiences with simultaneous combined radiation and cytostatic chemotherapy in the modification of intractable pain by inoperable tumor growth in the ENT area]. AB - Patients with malignant tumours of the ENT, who show signs of tumour progression after operation, radiation and chemotherapy, could be treated with a new combined therapy. We present a patient who was successfully treated by combined radiation and chemotherapy with Cisplatin, Ifosfamid, and BCNU. This therapy offers a chance of tumour reduction even for repeatedly treated patients. The relief of pain proves the success of the therapy. PMID- 2581107 TI - Feeding hospitalized children with developmental disabilities. PMID- 2581108 TI - [Serum anti-protease activity in the evaluation of results of proton hypophysectomy]. AB - The activity of the alpha 1-antitrypsin and alpha 2-macroglobulin were studied in 16 breast cancer patients and 25 hypophyseal adenoma patients prior to and at varying time after proton "hypophysectomy". A high alpha 1-antitrypsin level and a normal alpha 2-macroglobulin level were found in all the breast cancer patients. An increase in both blood serum inhibitors was detected in hypophyseal adenoma. The dependence of the alpha 1-antitrypsin content on a subclinical stage of generalized metastatic spread was revealed in the course of 2 years following "hypophysectomy" in the patients with disseminated breast cancer. In the hypophyseal adenoma patients the activity of both inhibitors returned to normal 1 year after treatment and remained within normal during 3 years of follow-up. It was regarded as a positive therapeutic effect. The above findings make it possible to propose the determination of the activity af alpha 1-antitrypsin in breast cancer and alpha 1-antitrypsin and alpha 2-macroglobulin in hypophyseal adenoma as an additional test for the evaluation of the results of proton "hypophysectomy". PMID- 2581106 TI - Chlorocyclohexane insecticides and male medfly attractants: similar stereospecificity for neuroactivity and interactions with a housefly [35S]t butylbicyclophosphorothionate binding site. AB - [35S]t-Butylbicyclophosphorothionate [( 35S]TBPS) undergoes saturable specific binding to a membrane preparation from housefly thoraxes and abdomens with apparent Kd and Bmax values at equilibrium of 0.17 microM and 2.2 pmol/mg protein at 20 degrees C. Lindane is more potent than three other isomers of hexachlorocyclohexane as a toxicant for houseflies and in displacing [35S]TBPS from this housefly membrane preparation. This correlation of similar stereospecificity for neuroactivity and interaction with the TBPS receptor extends to the Mediterranean fruit fly male attractant trimedlure and its components and analogs. The relative attractancy of t-butyl cis-4-chloro-trans-2 methylcyclohexanecarboxylate and of three less active isomers of this trans chlorocyclohexane-carboxylate parallel their potency in the [35S]TBPS binding assay. With both trimedlure and the related cyclohexene attractant siglure the trans-isomers are more potent than the cis-isomers as attractants and in displacing [35S]TBPS. Scatchard analyses indicate that lindane binds at the same site as [35S]TBPS. The hexachlorocyclohexane isomers and trimedlure components are much more potent inhibitors with membrane preparations from houseflies than from rat brain. The housefly TBPS receptor possibly serves as a model for the primary target sites, thereby suggesting that both the insecticide and the attractant may interact with some component of the putative GABAergic nervous or neuromuscular system. PMID- 2581109 TI - [Measles throughout the world]. AB - Measles is described according to two different environmental conditions: in industrialized countries and in developing countries. In the first case, it is usually accepted as a benign disease and the parents feel its set back mainly because of the absenteeism it causes. In the developing countries, its frequency and its severity induce the public as well as the health service officers to accept the heavy cost of mass campaign vaccination. The United States are next to the point of eradication and this goal should be one of the countries where measles are still a problem of public health. PMID- 2581110 TI - X-linked agammaglobulinemia: an analysis of 96 patients. AB - We have defined the clinical presentation and course of X-linked agammaglobulinemia (X-LA) by means of a multi-center retrospective survey of 96 patients. Infections were the most common presenting feature of patients with X LA. The most frequent infections involved the upper respiratory tract (75%), lower respiratory tract (65%), gastrointestinal tract (35%), skin (28%), and central nervous system (16%). Clinical clues to the diagnosis of X-LA were the chronic or recurrent nature of infections, a family history of immunodeficiency, and infections at more than one anatomic location. Infections remained a significant problem after the diagnosis of X-LA was made and gamma-globulin prophylaxis had been instituted. One or more chronic infectious diseases occurred in 71% of patients. The respiratory tract was the most common site of disease, and the gastrointestinal tract was relatively spared. Patients died at a mean age of 17 years. The two major causes of death were chronic pulmonary disease with resultant cardiac failure, and disseminated viral infections which characteristically caused a dermatomyositis-like syndrome, hepatitis, pneumonitis, and meningoencephalitis. PMID- 2581111 TI - Establishment of rat fetal liver lines and characterization of their metabolic and hormonal properties: use of temperature-sensitive SV40 virus. PMID- 2581112 TI - Assay for calcium channels. PMID- 2581113 TI - Monoclonal antibodies to gonadotropin subunits. PMID- 2581114 TI - Site specific monoclonal antibodies to insulin. PMID- 2581115 TI - Isolation and characterization of canine distemper virus-specific RNA. AB - Ten species of virus-specific RNA were detected in Vero cells infected with the FXNO strain of canine distemper virus (CDV). The largest RNA was the genome-sized RNA and the nine smaller species were polyadenylated RNAs. Similar results were obtained for nine other strains of CDV. The molecular weights of these ten RNAs were determined to be 4.61 X 10(6), 2.46 X 10(6), 1.52 X 10(6), 1.32 X 10(6), 1.19 X 10(6), 1.07 X 10(6), 0.77 X 10(6), 0.65 X 10(6), 0.58 X 10(6), and 0.48 X 10(6). By in vitro translation of the polyadenylated RNAs in a rabbit reticulocyte lysate system, three different proteins which probably correspond to H, NP, and M were synthesized from the fraction containing RNAs 7, 8, 9, and 10. PMID- 2581116 TI - Induction of interferon and activation of NK cells and macrophages in mice by oral administration of Ge-132, an organic germanium compound. AB - After oral administration of an organic germanium compound, Ge-132 (300 mg/kg), a significant level of interferon (IFN) activity was detected in the sera of mice at 20 hr and it reached a maximum of 320 U/ml at 24 hr. This IFN activity was lost after heat- or acid-treatment, suggesting that the induced IFN is of gamma nature. The molecular weight of this IFN was estimated to be 50,000 daltons by gel filtration. The NK activity of spleen cells was increased 24 hr after the oral administration of Ge-132, and cytotoxic macrophages were induced in the peritoneal cavity by 48 hr. In the mice receiving an intraperitoneal (ip) injection of trypan blue or carrageenan 2 days before oral administration of Ge 132, neither induction of IFN nor augmentation of NK activity occurred, and X-ray irradiation of mice also rendered the mice incapable of producing IFN, all indicating that both macrophages and lymphocytes are required for this IFN induction. Both NK and cytotoxic macrophages appeared 18 hr after ip administration of the induced IFN with a titer as low as 20 U/ml. These facts suggest that both the augmentation of NK activity and activation of macrophages in mice after oral administration of Ge-132 are mediated by the induced IFN. PMID- 2581118 TI - Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: XIII. Mutational and non-mutational mechanisms as subsets of a more general mechanism. Part B--hereditary tyrosinemia. AB - In this mini-series three different examples of the etiology for the induction of alpha-fetoprotein and hepatocarcinogenesis have been chosen. The first paper describes the mechanism using the non-mutagen, ethionine. In this paper the mechanism is derived by virtue of a mutation that causes a deficiency in fumarylacetoacetate fumarylhydrolase activity with subsequent accumulation of fumarylacetoacetate that is an inhibitor of ATP: L-methionine S adenosyltransferase. It is hypothesized that the chronically low levels of active methyl groups disallows base-pairing by the adenine moiety of S-adenosyl-L methionine and the repressed conformation of the alpha-fetoprotein gene is altered and subsequent transcription takes place. The same or similar process occurs with the subset of genes (embryonically repressed) that as a special group of active genes gives embryonic features to a quasi-differentiated stem cell causing "dysdifferentiation" to a neoplastic state. PMID- 2581117 TI - Opioid hypofunction in Parkinson's disease. AB - Loss of dopaminergic neuronal function has been the most consistent biochemical abnormality found in Parkinson's disease. Hypofunction of other transmitter systems has also been demonstrated in this disease. Recently, an opioid-dopamine link has been demonstrated. This paper provides evidence supporting an opioid system hypofunction in Parkinson's disease. PMID- 2581119 TI - Laser photocoagulation in obstructing malignant tumours of the respiratory and gastrointestinal tracts. AB - The palliation of obstructing malignant tumours of the respiratory tract and the gut is often inadequate. We report the endoscopic use of Nd-YAG laser photocoagulation for the rapid and safe relief of malignant obstruction in airways, colon and oesophagus in three patients. PMID- 2581121 TI - Subacute sclerosing panencephalitis. Current status. AB - Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disease of childhood that is due to a persistent measles infection. Owing to a nationwide immunization program in the United States, the incidence has decreased considerable, coexistent with the decline in natural measles infection. The disease, now fully understood, still represents a great international problem. Clinical presentation, etiology, pathogenesis, prevention, and treatment are updated in this article. PMID- 2581120 TI - [Aphthosis]. PMID- 2581122 TI - The putative M1 muscarinic receptor does not regulate phosphoinositide hydrolysis. Studies with pirenzepine and McN-A343 in chick heart and astrocytoma cells. AB - Muscarinic receptor activation stimulates phosphoinositide hydrolysis and inhibits cyclic AMP formation in dissociated embryonic chick heart cells. We used this preparation to examine the hypothesis that the putative M1 and M2 receptor subtypes are selectively coupled to these two responses. Atropine blocks the effects of carbachol on cyclic AMP formation and phosphoinositide breakdown with nearly identical KI values (1.9 and 0.8 nM); these values are close to the apparent KD (1.8 nM) of atropine competition for [3H]N-methylscopolamine binding. Pirenzepine blocks the effect of carbachol on cyclic AMP formation with a KI of 48 nM, a value similar to the apparent KD (23 nM) determined in radioligand binding studies. In contrast, a higher concentration of pirenzepine is needed to inhibit carbachol-stimulated phosphoinositide hydrolysis (KI = 255 nM). Two selective agonists, McN-A343 and AHR 602, inhibit cyclic AMP formation but do not stimulate phosphoinositide hydrolysis in chick heart cells. Muscarinic receptor mediated phosphoinositide hydrolysis in 1321N1 astrocytoma cells is also insensitive to McN-A343 or AHR 602 and is antagonized only by relatively high concentrations of pirenzepine. The M1 receptor, as previously defined, has high affinity for pirenzepine and is activated by McN-A343. We find that these ligands have greater activity at muscarinic receptors that inhibit cyclic AMP formation than at those that stimulate phosphoinositide hydrolysis. Thus, if different receptor subtypes are associated with these two responses, the M1 receptor regulates cyclic AMP rather than phosphoinositide metabolism. Our data also demonstrate that the chick heart has muscarinic receptors with high affinity for pirenzepine, and thus, in contrast to rat heart, appears to have predominantly M1 receptors. PMID- 2581123 TI - Conformational features of calcium channel agonist and antagonist analogs of nifedipine. AB - The crystal and molecular structures of methyl 2,6-dimethyl-5-nitro-4-(2 trifluoromethylphenyl)-1,4- dihydropyridine-3-carboxylate and ethyl 4-(2 difluoromethoxyphenyl)-1,4,5,7,-tetrahydro-2-methyl-5-oxof uro[3,4-b]pyridine-3 carboxylate, which are analogs of the calcium channel antagonist nifedipine reported to have agonist activity, have been determined. The conformations of these two agonists are compared with the conformational features shown by nifedipine and related 1,4-dihydropyridine calcium channel antagonists. Common conformational features shown by these agonists and antagonists allow both to bind to the same plasma membrane receptor while subtle differences in hydrogen bonding activity of the amine group, and ester group orientation and hydrophobic fit, may control the availability of channel open and closed states. PMID- 2581124 TI - Voltage clamp analysis of the inhibitory actions of diphenylhydantoin and carbamazepine on voltage-sensitive sodium channels in neuroblastoma cells. AB - The actions of diphenylhydantoin (DPH) and carbamazepine (CBZ) on sodium channels in mouse neuroblastoma cells (clone N18) were analyzed using the patch voltage clamp procedure in the whole cell configuration. DPH and CBZ reduced sodium currents without effect on the voltage dependence of sodium channel activation. Half-maximal inhibition was observed with approximately 30 microM of each drug. Depolarization increased and hyperpolarization reversed channel block by these two drugs in the voltage range from -90 to -45 mV. Repetitive stimulation at 2 Hz or greater enhanced inhibition of sodium channels. The half-time for recovery from voltage-dependent inhibition was greater for DPH (1.36 sec) than for CBZ (0.38 sec). A combination of prolonged depolarizing pulses of 15 mV with superimposed brief maximal depolarizations designed to mimic the electrical activity in an epileptic focus gave additive effects of voltage-dependent and frequency-dependent inhibition. The results support the previous proposal that DPH and CBZ are sodium channel-selective anticonvulsants and provide a potential basis for specific inhibition of neurons in epileptic foci. The mechanism of DPH and CBZ action is considered in terms of an allosteric or modulated receptor model of drug binding and action. PMID- 2581125 TI - Metabolic channeling of 5-fluoro-2'-deoxycytidine utilizing inhibitors of its deamination in cell culture. AB - The metabolism of 5-fluoro-2'-deoxycytidine (FdC) with and without tetrahydrouridine (H4U) or 2'-deoxytetrahydrouridine (dH4U) was examined in log phase HEp-2 cells using HPLC and TLC methods which quantified: the incorporation of FdC-related antimetabolites into RNA and DNA and pool size levels of FdC related antimetabolites. [3H]-FdC administered to log phase HEp-2 cells at a concentration of 0.01 microM for 24 hr resulted in the incorporation of 5.22 X 10(-8) mol of FdC/mol of DNA phosphate, a 0.021% substitution of FdC for dC. Coadministration of 1.0 mM H4U or dH4U resulted in 2- and 25-fold increases in the incorporation of FdC, respectively. No detectable incorporation of 5-fluoro 2'-deoxyuridine (FdU) into HEp-2 DNA resulted (detection limit, approximately 5 fmol). In contrast, treatment of HEp-2 cells with 0.1 microM FdU resulted in the incorporation of 1.83 X 10(-9) mol of FdU (74.7 fmol detected)/mol of DNA phosphate. A linear incorporation of FdC into the DNA of HEp-2 cells was found with increasing concentrations of FdC and 1.0 mM dH4U . 0.1 microM FdC resulted in the incorporation of 2.39 X 10(-6) mol of FUMP/mol of cytoplasmic RNA phosphate and 2.23 X 10(-5) mol of FUMP/mol of nuclear RNA phosphate. Similarly, HEp-2 cells treated with 0.1 microM FdU resulted in the incorporation of 1.10 X 10(-5) mol of FUMP/mol of nuclear RNA phosphate and 9.44 X 10(-7) mol of FUMP/mol of cytoplasmic RNA phosphate. In contrast, no detectable FUMP incorporation into either nuclear or cytoplasmic RNAs of HEp-2 cells resulted when H4U or dH4U was coadministered with 0.1 microM FdC. Pool size analyses of log phase HEp-2 cells following a 30-min exposure to FdU or FdC with and without H4U or dH4U were also performed; 0.1 microM FdC treatment resulted in the formation of 169 fmol of FUMP/1.0 X 10(6) viable HEp-2 cells. Treatment with 0.1 microM FdU produced 253 fmol of FUMP/1.0 X 10(6) viable HEp-2 cells. In contrast, no detectable FUMP pools were formed when H4U or dH4U was coadministered with 0.1 microM FdC (detection limit, approximately 5 fmol). Pool levels of FdUMP, the inhibitor of thymidylate synthetase, were also assayed; 36.9 fmol of FdUMP/1.0 X 10(6) viable HEp-2 cells were detected upon administration of 0.1 microM FdC.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2581128 TI - What is cancer surgery? PMID- 2581126 TI - Expression of c-Ki-ras, c-Ha-ras, and c-myc in specific cell types during hepatocarcinogenesis. AB - We examined the expression of six proto-oncogenes in (i) whole rat liver and isolated liver cell populations during the course of hepatocarcinogenesis induced by a choline-deficient diet containing 0.1% ethionine and (ii) fetal rat liver at different stages of development. The abundance of c-Ki-ras, c-Ha-ras, and c-myc transcripts in polysomal polyadenylated RNA from liver cells increased by 2 weeks after the start of the carcinogenic diet. c-Ki-ras and c-myc expression remained elevated during the 35 weeks of the diet, whereas c-Ha-ras transcripts increased transiently. A primary tumor sampled at 35 weeks after the carcinogenic diet was started contained high levels of both c-Ki-ras and c-myc RNA. The abundance of c src transcripts was unchanged throughout carcinogenesis; c-abl and c-mos transcripts were not detected in either preneoplastic or neoplastic livers. To determine which cell types within the liver contained proto-oncogene transcripts, we isolated hepatocytes, oval cells, and bile duct cells from normal and preneoplastic livers. The results indicate that proto-oncogenes are expressed differentially in these cell types during hepatocarcinogenesis and that the expression of c-Ki-ras and c-myc is high in oval cells throughout carcinogenesis. In developing livers, c-Ki-ras, c-Ha-ras, and c-myc transcript levels were high at 17 days of gestation but reached the low values characteristic of adult rat livers between 20 days of gestation and 3 days after birth. PMID- 2581127 TI - Isolation of duplicated human c-src genes located on chromosomes 1 and 20. AB - The oncogene (v-src) of Rous sarcoma virus apparently arose by transduction of the chicken gene known as c-src(chicken). We isolated DNA fragments representative of two src-related loci from recombinant DNA bacteriophage libraries of the human genome. One of these loci, c-src1(human), appeared to direct the synthesis of a 5-kilobase polyadenylated RNA that presumably encodes pp60c-src(human). Probes specific for the other locus, c-src2(human), did not hybridize to polyadenylated RNA prepared from a variety of human cell lines. Partial nucleotide sequence determinations of the loci demonstrated that c src1(human) is highly related to chicken c-src and that c-src2(human) is slightly more divergent. The sequences imply that the final two coding exons of each human locus are identical in length to those of chicken c-src and that the location of an amber stop codon is unchanged in all three loci. c-src1(human) has been mapped to chromosome 20, and the second locus is located on chromosome 1. We conclude that c-src1(human) is the analog of c-src(chicken) and that the duplicated locus, c-src2(human), may also be expressed. PMID- 2581129 TI - Involvement of DNA lesions and SOS functions in 5-bromouracil-induced mutagenesis. AB - Mutagenesis resulting from incorporation of 5-bromouracil (BU) in the DNA of E. coli K12 proceeds largely (approximately 80%) via misrepair of the lesions resulting from incorporation of the analogue. The premutational lesions are due principally to dehalogenation of incorporated BU residues, leading to formation of uracil residues, and removal of these by uracil-DNA glycosylase with formation of apyrimidinic sites. In the xthA mutant, defective in AP endonuclease, there is a several-fold increase in the frequency of BU-induced mutations, underlining the importance of AP sites in BU-induced mutagenesis. Premutational lesions undergo mutation frequency decline (MFD), which is subject to delay in the xthA mutant, pointing to some role of AP endonuclease in MFD, and further supporting involvement of AP sites in BU-induced mutagenesis. Efficient BU mutagenesis is dependent on the functions of the genes recA and umuC and non-mutated lexA protein. PMID- 2581130 TI - Reproductive performance and mutagenic response of the wasp Bracon hebetor following treatment with the antibiotic bleomycin. AB - Bleomycin (BM) induced dominant-lethal genetic lesions in the gametes of both sexes of adult Bracon hebetor wasps following ingestion. This effect was demonstrated by decreased fertility in the unfertilized eggs of treated females as well as in eggs fertilized by mature sperm derived from treated males. Death in the unhatched eggs occurred prior to blastoderm formation indicating BM caused chromosome breakage. Affected ovarian cells were limited to those exposed to BM between the developmental stages of vitellogenesis and early metaphase I. Sperm associated fertility reductions were temporary in duration with substantial reductions being observed starting on the second day following the initiation of oviposition. BM lowered general egg-formation capacity in treated females but, unlike the fertility effects, decreased fecundity was caused by somatic debility. Although the BM-induced genetic damage observed in B. hebetor was radiomimetic in nature, the time of appearance and duration of the effects did not correspond with previous patterns found when B. hebetor adults were exposed to X-rays. While the differences could be due to the BM detoxification or the repair of BM-induced chromosome damage, further investigation would be required to demonstrate the presence of such systems in this hymemopteran. PMID- 2581131 TI - Effect of 5-azacytidine (5-azaC) on the induction of chromatid aberrations (CA) and sister-chromatid exchanges (SCE). AB - Experiments were carried out using human lymphocytes from a male donor in order to test the action of 5-azaC treatment on the induction of SCE and chromatid aberrations. The 5-azaC was found to increase the frequency of both baseline and MMC-induced SCEs. Using the same 5-azaC treatment conditions it was found that the frequency of X-ray-induced CA did not increase. PMID- 2581132 TI - Keratinophilic fungi and dermatophytes in Lucknow soils with their global distribution. PMID- 2581133 TI - Subcellular fractionation of amoebapore and plasma membrane components of Entamoeba histolytica using self-generating Percoll gradients. AB - Separation and initial characterization of subcellular organelles from Entamoeba histolytica have been achieved by the use of self-generating Percoll gradients. Adequate resolution was obtained within one hour of amoeba homogenization. The ion-channel forming activity, amoebapore, was found associated with highly dense, small diameter particles, that were resolved from the numerous digestive vacuoles, and the plasma membrane. Following iodination of intact trophozoites with lactoperoxidase, the label was found to be incorporated into two distinct sedimentable fractions. The major component contained the near totality of the concanavalin A binding glycoproteins and the 5-iodonaphthalene-1-azide labelled intrinsic membrane proteins. It therefore was identified as the plasma membrane. The minor lactoperoxidase-iodinated component was found in the upper section of the gradient, associated with a particulate fraction nearly devoid of concanavalin A-binding glycoproteins. This fraction appears to represent particulate material on the external surface of the amoeba that is distinct from the plasma membrane. The digestive vesicles, which were identified by the presence of acid phosphatase and beta-D-glucosaminidase activities, appeared in the gradient as one main peak with a shoulder in the region of the plasma membrane. Analysis of the polypeptides and their labelling pattern in each fraction of the gradient are presented. Distinctive characteristics are discussed including the identification of a unique soluble protein highly labelled by 5 iodonaphthalene-1-azide. PMID- 2581135 TI - The clinical syndrome of striatal dopamine deficiency. Parkinsonism induced by 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). AB - Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a syndrome that resembles Parkinson's disease. To compare the biochemical abnormalities produced by this compound in human beings with those occurring in Parkinson's disease, we examined biogenic amine metabolites in cerebrospinal fluid and urine from six patients with MPTP-induced parkinsonism and eight patients with Parkinson's disease. In both forms of parkinsonism, the cerebrospinal fluid levels of homovanillic acid, the major metabolite of dopamine, were reduced, whereas the levels of the serotonin metabolite 5 hydroxyindoleacetic acid were normal. The cerebrospinal fluid levels of 3-methoxy 4-hydroxyphenylethylene glycol (MHPG), the major metabolite of norepinephrine in the brain, after adjustment for plasma MHPG, were elevated (greater than 6.0 ng per milliliter) in MPTP-induced parkinsonism, whereas MHPG levels were reduced (less than 6.0) in Parkinson's disease. Neurons containing norepinephrine in the brain are involved in the degenerative process of Parkinson's disease, whereas they are spared in MPTP-induced parkinsonism. The selective destruction by MPTP of nigrostriatal dopamine neurons that is responsible for the movement disorder also appears to result in an increase in central noradrenergic activity, which is not possible in Parkinson's disease. Thus, differences in central noradrenergic activity, reflected in cerebrospinal fluid levels of MHPG, distinguish these two forms of parkinsonism. PMID- 2581134 TI - Multiple non-repeated epitopes on the circumsporozoite protein of Plasmodium knowlesi. AB - The Plasmodium knowlesi circumsporozoite (CS) protein contains a repetitive immunodominant epitope. Here we show that the serum of rabbits repeatedly immunized with P. knowlesi sporozoites contains antibodies which bind to immobilized synthetic peptides ('C2', 'N2', and 'charged') representing two different polar regions of the CS polypeptide. These reactions are specific since the binding is inhibited only by the homologous peptides. Antisporozoite antibodies were isolated from the rabbit serum by affinity chromatography on Sepharose beads coupled to two synthetic peptides, 'C2' and 'charged'. Both purified antibodies recognized the CS protein and the intracellular precursors as shown by Western blotting analysis using sporozoite extracts. These results demonstrate that the corresponding areas of the native CS molecule are immunogenic, accessible to interaction with antibody, and therefore constitute potential targets for vaccine development. In addition, the present findings confirm the published amino acid sequence of a large portion of the CS protein which has been deduced from the nucleotide sequence of the corresponding gene. PMID- 2581136 TI - Antigenic analysis of influenza B virus isolated from the epidemic in 1973. PMID- 2581138 TI - Reverse transcriptase rides again. PMID- 2581137 TI - Expression of enhanced levels of small RNA polymerase III transcripts encoded by the B2 repeats in simian virus 40-transformed mouse cells. AB - Although specific viral genes are known which are sufficient to transform certain types of cells, viral transformation has been shown to be accompanied by a change in the level of expression of cellular genes. Assuming that this latter class of genes is involved in some way in the establishment of the transformed state, we and others have sought to characterize them. To this end, we constructed a complementary DNA library from a simian virus 40 (SV40)-transformed mouse cell line and screened this library for induced genes. Here we focus on the characterization of a specific cDNA clone called 10 lambda 5. We show that the clone 10 lambda 5 contains a B2 repeat, and that the levels of the small heterogeneously sized B2 cytoplasmic RNAs homologous to 10 lambda 5 are enhanced in transformed cells. Our studies show that these RNAs are a specific class of polymerase III transcripts containing a highly conserved 5' end. SV40 transformation results, therefore, in the activation of specific polymerase III transcripts as well as specific polymerase II transcripts. PMID- 2581139 TI - Gene rearrangement in cells with natural killer activity and expression of the beta-chain of the T-cell antigen receptor. AB - The mammalian host defence system can be divided broadly into adaptive and non adaptive immunity. Adaptive immunity is acquired and is mediated by B and T lymphocytes. Non-adaptive immunity is mediated in part by a small subclass of heterogeneous peripheral blood mononuclear cells. This population, termed null cells, consists of haematopoietic precursors and cells mediating natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC). NK cells are a class of non-adherent, non-phagocytic, rapidly cytotoxic lymphocytes which can efficiently lyse a wide variety of tumour cells, virally infected cells and immature cell types of normal origin. Despite the broad range of targets, only a limited number of specificities are thought to be involved in target-cell recognition. Morphologically, NK cells are large granular lymphocytes, but they have been shown to exhibit cell-surface markers characteristic of both T cells and monocytes, raising doubt over their lineage. The recent cloning of the beta chain of the T-cell antigen receptor has now allowed us to investigate whether some NK cells are T-cell-related. We have examined rearrangement and expression of the beta-chain of the T-cell receptor in cloned murine NK cell lines and fresh murine NK cell populations, and our results support the hypothesis that a subpopulation of NK cells is related to T cells and provide basis for examining whether some NK activity is mediated by a small number of T-cell receptors. PMID- 2581140 TI - Transient reversion of ras oncogene-induced cell transformation by antibodies specific for amino acid 12 of ras protein. AB - The proteins encoded by the ras oncogene are thought to trigger expression of the transformed phenotype in some types of cancer cells. In human cells, the ras protein family consists of several members including normal (proto-oncogene) and mutant (oncogene) forms. In general, the proto-oncogene forms are thought to be involved in the normal growth control of cells, while the mutant forms (which apparently result from somatic mutation of the normal ras genes) appear to be responsible, in part, for the loss of normal growth control. On microinjection into living normal cells, the purified ras oncogene protein (p21) induces a characteristic loss of growth control in cells within several hours. The mutant forms of the different ras proteins typically contain a single amino-acid change, usually at position 12 or less frequently at position 61. Here we report that microinjection of antibodies specific for amino acid 12 of the oncogenic v-Ki-ras protein into cells transformed by this protein causes a transient reversion of the cells to a normal phenotype. The fact that this antibody inhibits binding of GTP to the v-Ki-ras protein supports the notion that GTP binding is essential to the transforming function of this oncogene product. PMID- 2581141 TI - Dihydropyridine receptors in muscle are voltage-dependent but most are not functional calcium channels. AB - 1,4-Dihydropyridines are a new class of compounds believed to bind specifically and with high affinity to voltage-dependent calcium channels. They may be the first example of a ligand of use in the extraction and purification of the Ca channel. Although Ca channels and dihydropyridine receptors are found in many tissues, the richest and most convenient source is skeletal muscle. Functionally, 1,4-dihydropyridines such as nifedipine and nitrendipine block Ca channels; this effect is believed to form the basis for their clinical importance as Ca antagonists in relaxing vascular smooth muscle. But where currents through Ca channels can be measured directly, the block has required 100-1,000 times higher concentrations of dihydropyridine than necessary for the saturation of dihydropyridine binding sites. This discrepancy has remained unresolved because the study of pharmacological effects on Ca channels has required intact cells, while it has been difficult to investigate binding in other than cell-free preparations. Here we describe a method for measuring dihydropyridine binding to intact skeletal muscle and we compare our results with voltage-clamp measurements of Ca-channel block. We conclude that less than a few per cent of the binding sites in skeletal muscle represent functional Ca channels, contrary to general belief. PMID- 2581142 TI - Stimulation of connective tissue cell growth by substance P and substance K. AB - Connective tissue cells proliferate actively when cultured in the presence of serum. Platelet-derived growth factor (PDGF), a basic protein of relative molecular mass approximately 30,000, has been identified as the major serum mitogen for these cells; its main physiological/pathophysiological role may be to initiate wound healing in connection with tissue injury. However, growth of cultured cells is also influenced by several other factors, including epidermal growth factor, fibroblast growth factor, insulin and somatomedins. Furthermore, Rozengurt and Sinnett-Smith recently showed that bombesin, a neuroendocrine peptide isolated from frog skin, stimulates DNA synthesis and cell division in cultures of a specific subtype of 3T3 cells. Substance P and substance K (also known as neurokinin A or neuromedin L) are mammalian peptides belonging to the tachykinin family. Substance P has been studied extensively; it is distributed widely throughout the central and peripheral nervous system, including primary sensory neurones, and can be released in the periphery from axon collaterals of stimulated pain fibres and contribute to the inflammatory response. Substance K is a member of the tachykinin family isolated from mammalian spinal cord; Nawa et al. determined the primary structure of two types of substance P precursors, one of which contained a sequence homologous to substance K, as well as the sequence of substance P. We report here that substance P and substance K stimulate DNA synthesis in cultured arterial smooth muscle cells and human skin fibroblasts, and that this stimulation is inhibited by the substance P-antagonist spantide. PMID- 2581143 TI - Voltage dependence of Na/K pump current in isolated heart cells. AB - The Na/K pump usually pumps more Na+ out of the cell than K+ in, and so generates an outward component of membrane current which, in the heart, can be an important modulator of the frequency and shape of the cardiac impulse. Because it is electrogenic, Na/K pump activity ought to be sensitive to membrane potential, and it should decline with hyperpolarization. However, such voltage dependence of outward pump current has yet to be demonstrated, one reason being the technical difficulty of accurately measuring pump current over a sufficiently wide voltage range. The whole-cell patch-clamp technique allows effective control of both intracellular and extracellular solutions as well as membrane voltage. Applying this technique to myocardial cells isolated from guinea pig ventricle, we have measured Na/K pump current between -140 mV and +60 mV, after minimizing passive currents flowing through Ca2+, K+ and Na+ channels. We report here that strongly activated pump current shows marked voltage dependence; it declines steadily from a maximal level near 0 mV, becoming very small at -140 mV. Pump current-voltage relationships will provide essential information for testing models of the Na/K pump mechanism and for predicting pump-mediated changes in the electrical activity of excitable cells. PMID- 2581144 TI - Hepatitis B virus contains pre-S gene-encoded domains. AB - One of the open reading frames on hepatitis B virus (HBV) DNA comprises the coding region (designated the env gene) for the virus envelope proteins. Studies on messenger RNA transcription suggest that this gene has the potential to code for three related proteins: (1) a protein of 226 amino acids identified as a major protein constituent of the HBV envelope, termed S-protein; (2) a protein with 55 additional amino acids at the N-terminal coded for by a portion of the env gene upstream of the S-gene (pre-S); (3) a protein corresponding to the entire env gene (pre-S + S). Synthetic peptides from the N-terminals of proteins (2) and (3), and antisera to them have been used to study the occurrence and properties of pre-S sequences. The results presented here provide unambiguous evidence that all three env encoded proteins are present in HBV particles; synthetic peptides corresponding to the gene encoding pre-S are highly immunogenic and can be used in diagnostic tests for detection in human sera of antibodies preferentially recognizing HBV; such antibodies, specific for pre-S determinants, are elicited during hepatitis B infection and by immunization with HBV proteins (2) and (3); the hepatitis B vaccine licensed in the United States does not contain pre-S proteins; and the pre-S proteins of the HBV envelope contain domains specifically recognized by liver cells. These findings suggest that pre-S determinants are important in virus-neutralizing responses and should be present in HBV vaccines. PMID- 2581145 TI - The behavioral effects of the calcium agonist Bay K 8644 in the mouse: antagonism by the calcium antagonist nifedipine. AB - Mice injected with the calcium agonist BAY K 8644 (2-4 mg/kg, i.p.) displayed profound behavioral changes including ataxia, decreased motor activity, Straub tail, arched back, limb clonus and tonus, and an increased sensitivity to auditory stimulation. BAY K 8644 significantly impaired rotorod performance in mice with an ED50 of 0.8 mg/kg. The behavioral effects of BAY K 8644 were antagonized by nifedipine, but not by the non-dihydropyridine calcium channel antagonist verapamil or the alpha-adrenoceptor antagonist prazosin. Further, the actions of BAY K 8644 were not mimicked by the alpha-adrenoceptor agonist methoxamine at doses up to 4.5 mg/kg. These observations, coupled with the findings that BAY K 8644 is a potent, competitive inhibitor of [3H]nitrendipine binding to the dihydropyridine binding site in mouse brain (Ki = 7.0 X 10(-9) M), suggests that BAY K 8644 may produce its behavioral actions via an interaction with the DHP binding site, which has been linked to the control of calcium flux across membranes in peripheral tissues. PMID- 2581146 TI - The positive inotropic dihydropyridine Bay K 8644 does not affect calcium sensitivity or calcium release of skinned cardiac fibres. AB - BAY K 8644 is a positive inotropic dihydropyridine which concentration dependently increased contractile force in guinea-pig atria at 10 to 1000 nmol/l. In chemically skinned cardiac fibres from guinea-pig hearts the substance did not change the tension induced by calcium. Also BAY K 8644 did not release calcium from intracellular myocardial stores like caffeine since it failed to evoke a contractile response in saponin-treated, calcium-loaded cardiac muscle. Thus, the drug exerts its effects neither by sensitizing the contractile apparatus to calcium nor by a caffeine-like action. PMID- 2581147 TI - Cardiovascular profile of Bay K 8644, a presumed calcium channel activator, in the dog. AB - Bay k 8644, although belonging to dihydropyridines, has been reported to exert effects directionally opposite to those of dihydropyridine calcium channel blockers such as nifedipine. The present experiments were carried out to elucidate whether this is indeed true. All experiments were done on isolated, blood-perfused dog-heart preparations described below, and Bay k 8644 was administered intra-arterially. In sinoatrial (SA) node preparations Bay k 8644 increased sinus rate by about 37% of the basal value at the highest dose (10 micrograms). In atrioventricular (AV) node preparations Bay k 8644 decreased AV conduction time by accelerating AV nodal but not intraventricular conduction. However, the decrease in AV conduction time remained at about 10 ms (about 7.8% of the basal value) even at the highest dose (10 micrograms). In papillary muscle preparations driven at a fixed rate of 120 stimuli/min Bay k 8644 increased the force of contraction by about 100% of the basal value at the highest dose (10 micrograms). In spontaneously beating papillary muscle preparations Bay k 8644 failed to increase the rate of automaticity although it increased the force of contraction. In all preparations Bay k 8644 decreased (coronary) blood flow down to about 20% of the basal value at the highest dose (10 micrograms). The positive chronotropic and dromotropic effects of Bay k 8644 reached respective peaks nearly at the same time as its vasoconstrictor effect, whereas its positive inotropic effect reached a peak after the vasoconstrictor effect had nearly worn off.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581148 TI - The interaction of McN-A-343 with pirenzepine and other selective muscarine receptor antagonists at a prejunctional muscarine receptor. AB - The effect of several muscarine receptor antagonists on responses to carbachol (CCh) and McN-A-343 (McN) were compared in the perfused rabbit ear artery preparation stimulated via noradrenergic nerves at 3 Hz in the presence of cocaine (10 microM) and yohimbine (1 microM). The slope of the dose-response curve to McN was significantly less (P less than 0.05) than that for CCh although both agonists produced up to 100% inhibition of responses to nervous stimulation. All the antagonists investigated produced parallel shifts of the dose-response curve to the agonists and atropine, fenipramide or stercuronium gave a similar pA2 value with either agonist. Pirenzepine was a competitive antagonist when CCh was used, as judged by a slope of 0.96 +/- 0.10 for the Arunlakshana-Schild (A-S) plot (pKB 6.2). Displacement of 3H-(-)QNB binding by pirenzepine gave a pKI value of 6.0 which was not significantly different to the pKB value. When McN was used as the agonist, the dose-ratios obtained with pirenzepine (0.5 microM) were significantly different (P less than 0.01) to those with CCh as agonist and the slope of the A-S plot over the concentration range of 0.1 to 3 microM was significantly less than 1.0 (P less than 0.01), indicating that the inhibition was not a simple competitive interaction. It is suggested that the interaction of McN and pirenzepine may involve an allosteric mechanism. PMID- 2581149 TI - Substance P enteric neurons mediate non-cholinergic transmission to the circular muscle of the guinea-pig intestine. AB - The sites of action and possible roles of substance P in contracting the circular muscle of the guinea-pig ileum were studied using two analogues of substance P that act as antagonists of some of its actions. These are D-Arg1, D-Pro2, D Trp7,9, Leu11-substance P and D-Pro2, D-Trp7,9-substance P, referred to by the single letter amino acid codes for the substituting amino acids as (RPWWL)-SP and (PWW)-SP, respectively. Records of circular muscle activity were taken from strips of intestine free of mucosa and submucosa and from rings with all layers of intestine intact. Substance P was equally effective in contracting the circular muscle strips as it was in contracting the longitudinal muscle. The contractions of strips were not blocked by hyoscine (2 X 10(-6) M) or tetrodotoxin (6 X 10(-7) M), but were substantially reduced by (RPWWL)-SP (6.7 X 10(-6) M) or (PWW)-SP (2 X 10(-5) M). In contrast, contractions of the circular muscle of whole rings of intestine elicited by low concentrations of substance P (4 X 10(-7) M) were blocked by hyoscine or tetrodotoxin but not reduced by the substance P antagonists in the concentrations referred to above. These observations indicate that the antagonists are effective at receptors for substance P on the muscle, but not at substance P receptors on enteric cholinergic nerves. Transmural stimulation of strips of circular muscle or of intestinal rings in the presence of hyoscine evoked contractions that were blocked by tetrodotoxin. These hyoscine-resistant, nerve-mediated contractions could be elicited by single pulses in the strips.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581151 TI - [Reevaluation of postoperative thrombosis prevention]. PMID- 2581150 TI - Competitive interactions between Bay K 8644 and nifedipine in K+ depolarized smooth muscle: a passive role for Ca2+? AB - The kinetics of the interactions between Bay K 8644, a calcium channel activator, and the "calcium-antagonists" nifedipine, verapamil and diltiazem have been investigated. Nifedipine shifted cumulative concentration-response curves for Ca2+ to the right in K+ depolarized taenia preparations from the guinea-pig caecum. The apparent pA2 was 9.3 +/- 0.2 (slope 1.44; 95% confidence limits 0.99 1.88). Bay K 8644 (10-1,000 nmol/l) reduced the inhibitory effects of nifedipine, shifting the Schild plots to the right, without affecting the slope of the nifedipine:Ca2+ interaction. Thus, the interaction between the dihydropyridines was independent of external Ca2+. The parallel shifts of the Schild plots allow a novel interpretation of the "agonist" potency of Bay K 8644 because the compound had an apparent pA2 of 8.8 (slope 0.92) as an "antagonist" of the inhibitory effects of nifedipine. In contrast, Bay K 8644 was a non-competitive antagonist of the inhibitory effects of verapamil and diltiazem on Ca2+-induced contractions. These findings emphasize the differences between the various classes of "calcium-antagonists" and show that Bay K 8644 is a powerful tool discriminating between them. PMID- 2581153 TI - Effects of hypercapnia and papaverine on cerebrospinal fluid formation and choroid plexus blood flow. PMID- 2581154 TI - Chronological and volumetric changes in structures of the human brain in hemorrhagic cerebral infarction. PMID- 2581152 TI - Effect of hypothyroidism on the biogenesis of free mitochondria in the cerebral hemispheres and in cerebellum of rat during postnatal development. AB - The effect of propylthiouracil-induced neonatal hypothyroidism on some aspects of the biogenesis of free (non-synaptosomal) mitochondria in the cerebral hemispheres and in the cerebellum of developing rat has been studied. The results obtained show that in hypothyroid rats mitochondrial DNA synthesis is delayed, mitochondrial RNA synthesis is not affected and cytochrome aa3 content of mitochondria is lower than in controls. Furthermore ultrathin sections of 14- and 21-day old hypothyroid rat cerebella show mitochondria with an altered ultrastructural organization and large intracristal spaces. PMID- 2581155 TI - Increased risk of cerebral thrombo-embolic complication during gradual carotid artery occlusion combined with extra- and intracranial bypass surgery in the treatment of an inaccessible carotid aneurysm. PMID- 2581156 TI - The value of contrast-enhanced computed tomography for the diagnosis of intracranial aneurysms. PMID- 2581157 TI - Extravasation of contrast medium into blood clot in acute traumatic intraventricular hemorrhage. PMID- 2581158 TI - Chondrosarcoma in the optic canal--a case report with ultrastructural study. PMID- 2581159 TI - Acquired intracerebral toxoplasmosis presented as calcified mass lesions. PMID- 2581160 TI - Intracranial osteogenic sarcoma complicating Paget's disease of bone--case report. PMID- 2581161 TI - Neonatal orbital teratoma with intracranial extension--case report. PMID- 2581162 TI - Traumatic arteriovenous fistula of the scalp--report of two cases and review of the literature in Japan. PMID- 2581163 TI - Successful treatment of dwarfism and hypogonadism after total removal of craniopharyngioma. PMID- 2581164 TI - Effects of bromocriptine and radiation on the size and activity of estrogen induced rat prolactinomas. PMID- 2581165 TI - Progesterone-induced LHRH release in vitro is an estrogen--as well as Ca++- and calmodulin-dependent secretory process. AB - Mediobasal hypothalamic (MBH) slices of adult ovariectomized (OVX) rats with or without 17 beta-estradiol (E2) pretreatment, were superfused in buffered (pH 7.2) oxygenated Locke medium containing bacitracin. Pulsatile or continuous administration of progesterone (10(-7) or 10(-8) M) produced a marked increase in luteinizing hormone-releasing hormone (LHRH) release provided the animals had received E2 prior to sacrifice. Omission of Ca++ in the medium, or addition of a Ca++ channel blocker (D-600, 10(-4) M), of a calmodulin inhibitor (trifluoperazine, 30 microM) or of a calmodulin-dependent tubulin kinase inhibitor (phenytoin, 50 microM), antagonized the stimulatory effect of progesterone. When sodium channels were blocked by tetrodotoxin (5 X 10(-7) M), the stimulatory effect of the steroid was completely abolished. The amplitude of the K+-induced LHRH release was slightly increased in the presence of progesterone (10(-7) M) but only from MBH slices of OVX-E2-treated rats. These results indicate that the secretory response of LHRH to progesterone requires priming with estradiol, is Ca++-dependent and involves mediation of calmodulin and a calmodulin-dependent kinase system. PMID- 2581166 TI - Release of mast cell mediators, vasoconstriction and edema in the isolated, perfused head of the rat following intracarotid infusion of neurotensin. AB - Intracarotid infusions of neurotensin (NT) into the isolated, perfused head of rats trigger concentration-dependent histamine and 5-hydroxytryptamine (5-HT) release from the perfused organ. The secretory event was accompanied by a concentration-dependent rise in perfusion pressure and facilitation of edema formation. The three NT effects were markedly reduced in heads derived from rats pretreated with high doses of compound 48/80 to produce mast cell depletion. The vasoconstrictor response to NT was greatly attenuated by the 5-HT receptor antagonist methysergide but unaffected by antihistaminic drugs. The results were interpreted as an indication that NT stimulates histamine and 5-HT release from mast cells of the rat perfused head. The results also suggest that the vasoconstrictor response to NT in the rat head is mediated by mast cell 5-HT. The potentiation of edema formation by NT was attributed to the action of mast cell mediators (most likely histamine and 5-HT) released by NT on microvessels. PMID- 2581167 TI - Pharmacological characterisation of two tachykinin binding sites in the rat cerebral cortex. AB - The pharmacological properties of two types of tachykinin receptor were characterised on rat cortical synaptosomes using 125I-Bolton Hunter substance P (125I-BHSP) or with 125I-Bolton Hunter eledoisin (125I-BHE). Shorter SP C terminal fragments, such as SP (6-11) or (pGlu)-SP (6-11), were more potent than SP itself or longer SP C-terminal fragments in competing for 125I-BHE binding; their efficacy was comparable to that of eledoisin. In contrast, longer SP C terminal fragments exhibited a higher affinity than shorter ones for the 125I BHSP binding sites as previously reported. SP N-terminal fragments were devoid of activity on either type of binding sites. SP methyl ester inhibited 125I-BHSP binding but was without effect on 125I-BHE binding whilst, DiMe-C7, a metabolically stable tachykinin analog, had the opposite selectivity. Eledoisin related peptide (ERP) was less effective than either SP or eledoisin on 125I-BHSP and 125I-BHE binding sites respectively. Finally, the undecapeptide or octapeptide SP antagonists, which are weak inhibitors of 125I-BHSP binding, had negligable activity on 125I-BHE binding sites. PMID- 2581168 TI - Retrograde localization of the innervation of the middle cerebral artery with horseradish peroxidase in cats. AB - The innervation of the middle cerebral artery (MCA) of the cat was studied by applying horseradish peroxidase (HRP) to the wall of the right MCA. After a survival period of 48 to 72 hours, the bilateral superior cervical ganglia, middle cervical ganglia, stellate ganglia, T-4 sympathetic paravertebral ganglia, geniculate ganglia, semilunar ganglia, nodose ganglia, and brain stem including midbrain, pons, and medulla oblongata were removed to be processed with tetramethyl benzidine. HRP-labeled neurons were found in the ipsilateral superior cervical ganglion, semilunar ganglion, and dorsal raphe nucleus. The other areas did not have HRP activity. The results suggest that the adrenergic nerves innervating the MCA originate in the ipsilateral superior cervical ganglion, the sensory nerves originate in the ipsilateral semilunar ganglion, and the serotonergic nerves originate in the ipsilateral dorsal raphe nucleus. Cerebral arterial constriction may relate to the intrinsic (intracerebral) neurogenic pathway involving the trigeminal nerve and the dorsal raphe nucleus. PMID- 2581169 TI - Immunohistochemical studies of substance P, cholecystokinin-octapeptide and somatostatin in dorsal root ganglia of the rat. AB - Immunofluorescence histochemistry was used to determine the distribution of substance P, somatostatin and cholecystokinin-octapeptide-immunoreactive perikarya in C6, T6, T10, L2 and S1 dorsal root ganglia of rat. Five different categories of immunoreactive primary afferent neurons were distinguished on the basis of cell size, cytology and peptide immunoreactivities. The population of small cells (diameter less than 20 microns) included three groups which were identified as containing somatostatin, substance P, or substance P + cholecystokinin-octapeptide. Two groups of cells were identified in an intermediate size range (diameter 21-43 microns) as containing cholecystokinin octapeptide or cholecystokinin-octapeptide + substance P. These categories may reflect four distinct populations of primary afferent neurons. The relative abundance of dorsal root ganglion cells containing substance P, cholecystokinin octapeptide or somatostatin immunoreactivities was significantly different within segmental levels. More neurons were immunoreactive for cholecystokinin octapeptide than substance P in ganglia C6, T6 and T10. Somatostatin-containing cells were fewest in number regardless of level. The number of immunoreactive cells also varied among spinal ganglia. L2 contained the greatest number of immunoreactive cells; S1 contained the fewest. These studies are relevant to our understanding of dorsal root ganglia in two ways. Firstly, the data document significant variation in the distribution of peptide-containing neurons among spinal ganglia associated with various cord levels. The variation in peptide containing cell populations among spinal ganglia may reflect differences in populations of modality-specific primary afferent fibers as well as in populations of somatic and visceral primary afferent fibers at each level. Furthermore, the data indicate that the relative abundance of a population of peptide-containing primary afferent neurons cannot be extrapolated from the examination of spinal ganglia from a single level. Secondly, substance P and cholecystokinin-octapeptide did not co-exist in all spinal ganglion cells as previously reported. In conjunction with immunostaining characteristics and cell size, the differential distribution of the two peptides defined four cell types, raising the possibility that each cell type may mediate a different modality. PMID- 2581170 TI - Localization and axonal transport of immunoreactive cholinergic organelles in rat motor neurons--an immunofluorescent study. AB - Antisera produced in rabbits against pure fractions of cholinergic vesicles from Narcine brasiliensis were used to study cholinergic organelles in rat motor neurons. The indirect immunofluorescence method was used on perfusion-fixed material. The rats were surgically sympathectomized to remove sympathetic adrenergic and cholinergic nerves from the sciatic nerve. In the intact animal immunoreactive material, likely to represent cholinergic vesicles, was observed in motor endplates, identified by labelling with rhodamine-conjugated alpha bungarotoxin or with subsequent acetylcholinesterase staining. The motor perikarya contained very little immunoreactive material. Non-terminal axons were virtually devoid of immunofluorescence in the intact animal. After crushing the sciatic nerve, immunoreactive material (likely to represent axonal cholinergic organelles) accumulated rapidly on both sides of the crush, indicating a rapid bidirectional transport. The transport was sensitive to local application of mitotic inhibitors. The axons which accumulated immunoreactive organelles were motor axons, as demonstrated by various procedures: Cutting of ventral roots prevented accumulation of immunoreactive material in the nerve. Deafferentation did not notably influence accumulations of immunoreactive material. Ligated axons with immunoreactive material were acetylcholinesterase positive when identification was made on the same section; the intra-axonal distribution of immunoreactive material and acetylcholinesterase was not identical, however, and the Narcine antisera did not cross-react with bovine acetylcholinesterase in a solid phase immunoassay. Most axons in ventral roots, but not in dorsal roots, accumulated strongly fluorescent immunoreactive material, while axons in dorsal roots contained weakly fluorescent material. On the other hand, substance P-like immune reactivity was present in many dorsal root axons, but only very rarely in ventral roots. It is suggested that the antisera against Narcine cholinergic vesicles can be used as a marker for cholinergic organelles in the motor neuron, and may be an important tool for studying the axonal cholinergic vesicles. It cannot, however, be used to identify cholinergic structures in unknown locations because it recognizes common antigenic determinants in transmitter organelles of other nerves, e.g. adrenergic nerves. The axonal cholinergic organelles may carry important molecules, other than acetylcholine to the nerve endings. PMID- 2581171 TI - Substance P acts by releasing 5-hydroxytryptamine from enteric neurons in the stomach of the rainbow trout, Salmo gairdneri. AB - The effect and mode of action of substance P was studied in a perfused stomach preparation and on isolated strip preparations of the stomach wall from the rainbow trout, Salmo gairdneri. Substance P was excitatory on the stomach muscle wall in a dose-dependent manner. Two other tachykinins, physalaemin and eledoisin, excited the preparations in a similar manner and in the same dose range. The effect of substance P was not antagonized by the substance P analogues [D-Pro2, D-Phe7, D-Trp9]substance P and [D-Pro2, D-Trp7,9]substance P (both 10( 5) M). Tetrodotoxin reduced or abolished the effect of substance P, while no reduction of the response was obtained after atropine, chlorisondamine or phentolamine (all 10(-6) M). 5-Hydroxytryptamine excited the stomach and this effect was not antagonized by tetrodotoxin, suggesting that the action of 5 hydroxytryptamine was direct on the smooth muscle. The 5-hydroxytryptamine antagonist methysergide, in a concentration which selectively blocked the response to 5-hydroxytryptamine, also blocked the response to substance P (10(-9) 10(-8) M). The outflow of 5-[3H]hydroxytryptamine from a preloaded perfused stomach was clearly increased by substance P, and this release was blocked by tetrodotoxin. Immunohistochemistry revealed the presence of nerve fibres and ganglion cells showing 5-hydroxytryptamine-like immunoreactivity in the myenteric plexus and smooth muscle layers of the stomach wall. The immunoreactive cells and nerve fibres were particularly abundant in the pyloric part of the stomach. It is concluded that the main effect of substance P on the stomach wall of the rainbow trout is indirect, via activation of a non-adrenergic, non-cholinergic neuron. The results are compatible with the view that this neuron exerts its action by release of 5-hydroxytryptamine. Supramaximal concentrations (greater than or equal to 10(-7) M) of substance P may in addition have a direct effect on the gastric smooth muscle. PMID- 2581172 TI - Cell-cell junctional interactions and characteristic plasma membrane features of cultured rat glial cells. AB - Mixed cultures of astrocytes and oligodendrocytes derived from cerebral hemispheres of 18-19 day old rat fetuses were studied with the freeze-fracture technique. The plasma membranes of cultured astrocytes and oligodendrocytes differ substantially in their intramembrane particle profiles, and they can be positively identified consistently. Orthogonal small particle assemblies and numerous isolated globular particles characterize astrocytic plasma membranes, whereas the plasma membranes of oligodendrocytes show numerous elongated particles and fewer large and small globular particles similar to those seen in situ. Using these distinct differential features, we can identify partners of glial cell junctions. We can identify numerous interastrocytic gap junctions, as well as heterologous astrocyte-to-oligodendrocyte gap junctions. The plasma membranes of adjacent oligodendrocytes form numerous tight junctions consisting of linear P face strands and/or rows of particles interrupted by short segments of grooves, the complementary features on the E face. "Reflexive" type tight junctions seen in situ are also observed. In addition to intercellular junctions, glial cells develop special plasma membrane structural domains. Astrocytic plasma membranes often contain groups of plasmalemmal vesicles (caveolae), a distinctive feature of astrocytes in situ. Oligodendrocytes form flattened velate processes with cytoplasm restricted to finger-like channels resembling myelin lamellae in situ. Cultured astrocytes and oligodendrocytes develop the entire range of plasma membrane structural specializations seen in situ in the absence of the normal brain tissue framework. Thus, primary glial cell cultures allow experimental study of many glial cell properties, including their plasma membrane specializations. PMID- 2581173 TI - Comparison of substance P and enkephalin distribution in rat brain: an overview using radioimmunocytochemistry. AB - The distribution of substance P and leucine enkephalin in mid- and fore-brain areas of the rat was studied using a radioimmunocytochemical method. The secondary antibody was labeled with 125I and the sections apposed to LKB Ultrofilm or emulsion-dipped. In alternate sections an extensive distribution of substance P and enkephalin immunoreactive material was seen in frontal, cingulate, retrosplenial, and entorhinal cortices. Substance P and enkephalin exhibited a remarkable overlap in many of these cortical areas as well as in the nucleus accumbens, caudate, portions of the hypothalamus, amygdala, thalamus and central gray. Differences in distribution were seen in the retrosplenial cortex, septum, ventromedial hypothalamus, hippocampus, the substantia nigra and the superior colliculus. The results provide a detailed immunohistochemical demonstration of the laminar patterns of substance P and enkephalin in the cortex of the rat. The results are discussed in terms of the interaction of substance P and enkephalin. The matches and mismatches of immunoreactive substance P and enkephalin and the locations of their receptors are also examined. PMID- 2581174 TI - Effects of glutamate, substance P and eledoisin-related peptide on solitary tract neurones involved in respiration and respiratory reflexes. AB - Recent studies have implicated glutamate and substance P in synaptic transmission in the nuclei tractus solitarii and in central regulation of cardiorespiratory functions. Consequently, in chloralose-anaesthetized cats that were artificially ventilated, we examined the effects of the microiontophoretic application of both chemicals (and the substance P homologue, eledoisin-related peptide) on single neurones of the nuclei tractus solitarii implicated in the control of respiration and respiratory tract reflexes. These neurones were functionally identified as either respiratory neurones or presumed reflex interneurones, and showed functional properties comparable to those previously documented for each of these two types. The iontophoretic application of glutamate produced an excitation of rapid onset in 23 or 25 reflex interneurones tested, but the respiratory neurones showed a differential sensitivity: one type (n = 32) was "glutamate-sensitive" and showed rapid excitation with glutamate applications of less than 30 nA, the other type of respiratory neurone (n = 26) was termed "glutamate-insensitive" since it either showed excitation only with applications of 60 nA or more or showed no response even with currents up to 94 nA. Each neurone studied was clearly of one type or the other. Glutamate could increase the number of spikes per rhythmic burst and the burst duration of respiratory neurones, it facilitated evoked activity in the reflex interneurones and in those respiratory neurones having a superior laryngeal nerve or vagus nerve afferent input, and the magnitude of the excitatory responses to glutamate varied directly with the amount of ejecting current. Substance P and eledoisin-related peptide also had excitatory effects on respiratory neurones and reflex interneurones, but compared with glutamate-induced effects the excitation was slower in onset and more prolonged in after-discharge. Both rhythmic and evoked activity could be facilitated, and the magnitude of the effect varied directly with the magnitude of the ejecting current. In showing that both glutamate and substance P (and its analogue, eledoisin-related peptide) have excitatory effects on the activity of respiratory neurones and reflex interneurones, this study provides evidence suggesting that these neurones have receptors for these neural chemicals, supportive of a role for each chemical in the regulation of respiration and respiratory tract reflexes. PMID- 2581176 TI - beta-Adrenergic treatment of hyperkalemic periodic paralysis. AB - In a patient with hyperkalemic periodic paralysis, metaproterenol prevented muscular weakness and hyperkalemia in periods of rest after exercise. During a severe attack, the drug rapidly corrected hyperkalemia and seemed to enhance the return of strength. The action of metaproterenol may involve a beta-adrenergic mediated increase of potassium transport via the sodium-potassium pump. PMID- 2581175 TI - Excitatory amino acid-induced responses of frog motoneurones bathed in low Na+ media: an intracellular study. AB - Motoneurones of the frog spinal cord slice preparation were impaled with microelectrodes and superfused at 7 degrees C with the excitatory amino acids glutamate, quisqualate or N-methyl-D-aspartate. The role of Na+ in the action of these amino acids was studied by comparing amplitude matched depolarizations obtained in control Ringer solution with the responses recorded from the same cells after replacing (86-100%) Na+ by choline or glucosamine. Effective replacement of extracellular Na+ proved to be a rather slow process requiring 30 60 min. In glucosamine solution depolarizations evoked by glutamate, N-methyl-D aspartate or quisqualate were abolished or strongly reduced with recovery following return to control Ringer. In choline solution, glutamate and N-methyl-D aspartate effects were blocked whereas the quisqualate response was surprisingly unaffected. Mn2+ (2 mM) added to choline solution strongly diminished the action of quisqualate. These results suggest that Na+ was important in mediating amino acid responses and that quisqualate activated an additional conductance mechanism (perhaps to Ca2+) unmasked only in choline-containing solution. PMID- 2581177 TI - [Local recurrence after surgery of cancer of the rectum. Risk factors, diagnostic and therapeutic possibilities]. PMID- 2581178 TI - ["Selected" anorectal cancers and cryosurgery. Indications, technics and results of an experience]. PMID- 2581179 TI - [Sodium transport in chronic renal insufficiency]. AB - From an analysis of the literature covering the problem of sodium contribution in uraemic patients subjected to both conservative treatment and maintenance dialysis, it has been shown that excessive reduction in dietary sodium intake can be harmful unless it is justified by severe hypertension or oedema since it aggravates the state of uraemia. In these cases, the addition of a minimum controlled amount of hyposodic salt to an otherwise salt free diet is undoubtedly useful. The hyposodic salt, "Misura" manufactured by the company "Plasmon" was used in the dietary treatment of a series of patients subjected to mild restriction in dietary salt intake. Misura was well tolerated and well accepted thanks to its pleasing taste. PMID- 2581180 TI - [A case of reconstruction of the cervical esophagus in wound dehiscence resulting from esophagogastric anastomosis at the neck level]. PMID- 2581182 TI - Acetylcholine-induced currents at plasma membrane of the frog oocyte. AB - Although with remarkable variability, membrane permeability in Rana oocytes can be modified by application of acetylcholine. The experiments were carried out in voltage-clamp conditions. Like in Xenopus, the responses proved to be related to activation of muscarinic receptors operating membrane channels probably selective for Cl-. At differences with Xenopus, the net acetylcholine-induced current showed remarkable deviation from linearity, displaying outward-going rectification. Application of acetylcholine typically produced opening of membrane channels, while in late spring, we observed the opposite effect in several batches of oocytes. PMID- 2581181 TI - Opiate and histamine H1 receptors are present on some substance P-containing dorsal root ganglion cells. AB - Using combined immunohistochemical and receptor binding techniques, substance P containing sensory neurones of rhesus monkey cervical dorsal root ganglia were examined for the presence of opiate or histamine (H1) receptors. Serial sets of three sections were examined sequentially for substance P-containing neurones, opiate receptors using [3H]etorphine binding and histamine (H1) receptors using [3H]mepyramine binding. Of 3484 dorsal root ganglion cells, 513 contained substance P. Of 30 randomly chosen substance P-positive neurones, 6 possessed opiate receptors and 7 histamine receptors, including 4 neurones with both sets of binding sites. The results are interpreted to suggest that both nociceptors and non-nociceptive sensory inputs may be biochemically heterogeneous and that a simple correlation between substance P content and a particular receptive field profile is unlikely. PMID- 2581184 TI - Substance P concentrations in human cerebrospinal fluid vary inversely with age. AB - The mean concentrations of immunoreactive substance P in cerebrospinal fluid (CSF) of 10 fetuses (gestational age 11-20 weeks) were 22.7 +/- 8.3 pmol/ml, compared with 250.0 +/- 28.2 fmol/ml in premature babies (gestational age 25-31.5 weeks, n = 8), 141.0 +/- 14.2 fmol/ml in full term newborn babies (n = 5), 50.0 +/- 2.3 fmol/ml in children (age 1-6 years, n = 6), and 9.5 +/- 1.5 fmol/ml in 5 adults. The differences between successive age groups were all statistically significant. The high concentration of substance P in human CSF in the early stages of development and its continuous decline towards maturity encourages the idea that substance P plays a role in neuro-development. PMID- 2581183 TI - Monoclonal cell surface antibodies do not produce short-term effects on electrical properties of mouse oligodendrocytes in culture. AB - Eleven monoclonal antibodies (O1-O11) directed against the surface of oligodendrocytes were applied individually or in combination during measurement of membrane potential, input resistance and K+-pump activity in explant cultures of mouse spinal cord. Antibody binding to oligodendrocytes was verified by indirect immunofluorescence. None of the antibodies affected the electrical properties studied. On the basis of these observations, it is possible to identify oligodendrocytes immunocytologically prior to electrophysiological characterization. PMID- 2581185 TI - Stereoselectivity of L-baclofen in hippocampal slices of the rat. AB - Extra- and intracellular recording from hippocampal slices of the rat revealed the following effects when baclofen (BF) (0.1-10 microM) was added to the perfusion fluid: a block of synaptic potentials evoked by stimulation of stratum radiatum; a direct hyperpolarization and a conductance increase (for potassium ions) of CA1 pyramidal cells. All this activity was found in the L- none in the D enantiomer. D-BF did not antagonize the action of L-BF. PMID- 2581186 TI - Mesencephalic pathway to the retina exhibits enkephalin-like immunoreactivity. AB - Using immunocytochemical methods it was possible to demonstrate a small number of fibers within the optic nerve of the turtle Pseudemys scripta elegans exhibiting Met-enkephalin-like immunoreactivity. The fibers project to the retina where they ramify within the inner plexiform layer in the region of the visual streak. Retrograde labelling with Nuclear Yellow in combination with immunocytochemical staining revealed the origin of these fibers within visceral nuclei of the caudal mesencephalon. The existence of a mesencephalic, enkephalinergic pathway to the retina will facilitate further studies of opiate action in the retina by offering the possibility of selectively stimulating the endogenous release. PMID- 2581188 TI - Effect of light on Na-Ca exchange in rod outer segments in frog. AB - The effect of illumination on the calcium (Ca) translocation mechanisms in isolated frog rod outer segments (ROS) was studied. The ATP-dependent Ca uptake and the Ca-Ca exchange mechanisms were unaffected by light. In contrast, we report a light-evoked Ca efflux which is mediated by the Na-Ca exchange system. The ratio of released Ca to rhodopsin bleaching was measured and the stoichiometry obtained was 5 Ca molecules released per mole of rhodopsin bleached. Concomitant to the Ca release, light induced Ca uptake, which increase the total Ca content of ROS. Physiological relevance of results to the phototransduction process is discussed. PMID- 2581187 TI - Effects of substance P antagonists on the atropine-sensitive and atropine resistant responses of guinea-pig ileum to substance P. AB - The effects of substance P (SP) antagonists on the atropine-sensitive and atropine-resistant responses to SP of guinea-pig isolated ileum were investigated. The atropine-resistant response to SP was the contractile response on untreated preparations, and the atropine-sensitive response was the response to high concentrations of SP (5 X 10(-7) M) on preparations desensitized to SP with a concentration of SP of 3 X 10(-7) M. The SP antagonists tested, (D-Pro2,D Phe7,D-Trp9)-SP, (D-Pro2,D-Trp7,9)-SP, (D-Arg1,D-Pro2,D-Trp7,9,Leu11)-SP and (D Arg1,D-Trp7,9,Leu11)-SP (spantide), did not have similar orders of potency on the atropine-sensitive and atropine-resistant responses to SP, spantide being more potent than the other antagonists on the atropine-resistant response but no more potent on the atropine-sensitive response than (D-Pro2,D-Phe7,D-Trp9)-SP or (D Arg1,D-Pro2,D-Trp7,9,Leu11)-SP. These findings are consistent with the hypothesis that neuronal receptors for SP differ from those on smooth muscle in guinea-pig ileum. PMID- 2581189 TI - The effects of capsaicin on action potential and outward potassium currents in a bursting neuron of the snail, Helix pomatia L. AB - The effects of capsaicin (CAP) on membrane properties, action potentials (APs) and outward membrane currents were investigated using the single electrode current and voltage clamp. CAP (60-300 microM) depolarized the cell membrane and increased the input resistance (Rin). The burst frequency of the neuron simultaneously increased. CAP prolonged the APs and attenuated the outward currents with decreasing potency in the sequence of the early outward current (IA), an early and a late component of the delayed outward current. PMID- 2581190 TI - An electron microscopic study of alterations in mouse peripheral nerve and skeletal muscle after chlordecone exposure. AB - Skeletal muscle and peripheral nerve of mice exposed to subacute doses of chlordecone were examined by electron microscopy to characterize the induced pathology. Adult mice were given daily ip doses of chlordecone for 8 days, then sacrificed on days 8, 15, and 35 of the experiment. Sciatic nerve and gluteal muscle were removed and prepared for electron microscopic examination. In peripheral nerve the most common effect was vesiculation of the cytoplasm of Schwann cells associated with unmyelinated fibers. Some unmyelinated axons were swollen and their microtubules and neurofilaments were replaced by flocculent material. In other unmyelinated axons some mitochondria contained paracrystalline inclusions. Myelinated axons, myelin, and associated Schwann cells were generally unaffected by the chlordecone. In skeletal muscle, during more acute phases of exposure, mitochondrial envelopes increased in density, cristae structure was altered, and membranous whorls were formed in or adjacent to the mitochondria. Glycogen and lipid deposits were decreased in acute phases. During the recovery phase glycogen, lipids and mitochondria reassumed normal structure. PMID- 2581191 TI - The basal ganglia in chlordecone-induced neurotoxicity in the mouse. AB - This overview summarizes the available data concerning the neurotoxic effects of chlordecone on the basal ganglia in mice. Included are the effects of chlordecone on motor coordination, levels of biogenic amines, uptake of catecholamines and GABA, release of 3H-dopamine from striatal slices, newly synthesized dopamine, levels of dopamine metabolites in striatum, total and protein-bound Ca++ in discrete areas of brain, and distribution of chlordecone in discrete areas of brain. These data suggest that the basal ganglia may be the brain site at which chlordecone acts to produce its neurotoxic effects. PMID- 2581192 TI - Chlordecone interaction with catecholamine binding and uptake in rat brain synaptosomes. AB - The in vitro and in vivo effects of chlordecone on rat brain synaptosomal binding and uptake of 3H-dopamine and 3H-norepinephrine were determined. The data show that chlordecone decreases both binding and uptake of the 3H-catecholamines in vitro and in vivo. The uptake of 3H-dopamine was more sensitive to chlordecone than binding. 3H-norepinephrine binding and uptake was decreased to a lesser degree as compared to dopamine. In general, chlordecone at about 25-50 microM concentration produced a 50% decrease of the ligands binding and uptake. Mirex, a non-neurotoxic compound and a structural analog of chlordecone altered neither binding nor uptake of the ligands tested. These studies suggest that chlordecone may be modulating the pre and post synaptic function. PMID- 2581194 TI - Effects of perinatal Kepone exposure on sexual differentiation of the rat brain. AB - Timed-pregnant Sprague-Dawley rats were injected intraperitonealy with Kepone dissolved in sesame oil on alternate days beginning on day 18 of gestation and extending through day 7 of lactation with doses of 10 or 5 mg/kg. At 7 days of age the neurologic development of the pups was assessed using the following tests: day of eye opening, occurrence of auditory startle, righting response, reflex suspension, tactile forelimb-placing response, negative geotaxis, and open field activity. At 70 days of age, vaginal washes from female offspring were examined microscopically for evidence of cyclic activity. At 120 days of age, animals were sacrificed and the brains were examined histologically and the volume of the medial preoptic nucleus was determined. The results indicated that exposure of rat pups to Kepone via either placental and/or milk transfer can result in an acute, or transient, impairment of neurologic development and a possible permanent neuroendocrine impairment. The permanent neuroendocrine dysfunction may be similar to the androgenization phenomenon (i.e., female pups exposed to sex steroids during development) and thus may be related to the reported estrogenic properties of Kepone. PMID- 2581193 TI - Effects of chlordecone administration on brain and pituitary peptide systems. AB - It has been clearly demonstrated that chlordecone exerts estrogen-like effects on the reproductive system. However, the extent to which the estrogenic activity of this neurotoxicant may contribute to its central nervous system effects is not clear. The purpose of this study was to compare the estrogenic activity of chlordecone and estrogen on the rat hypothalamo-pituitary axis (HPA) by using the pituitary enkephalin system as a model. It was found that the enkephalin system of the anterior pituitary is regulated by circulating estrogen. Ovariectomy caused an increase in the pituitary content of enkephalin and this increase was prevented by estrogen treatment. Administration of estrogen reduced the pituitary content of this peptide in intact male rats. Similarly, chlordecone treatment reduced the pituitary content of enkephalin in a manner identical to that of estrogen. A single injection of chlordecone (75 mg/kg; i.p.) caused a delayed decrease in the enkephalin level of the anterior lobe (but not the posterior lobe) of the pituitary. This effect of chlordecone was selective to male rats since the pituitary enkephalin level of females was not altered by such treatment. Levels of other pituitary hormones such as beta-endorphin, vasopressin, etc., were not decreased. Further studies revealed that the similarities between chlordecone and estrogen could be extended to other pituitary hormones. For example, implantation of estrogen or of chlordecone in ovariectomized rats caused similar changes in serum prolactin and luteinizing hormone levels. Thus, this study demonstrates a clear estrogen-like action of chlordecone on the HPA. Moreover, due to the similarity of both estrogen and chlordecone to anti-dopaminergic agents in altering [Met5]-enkephalin levels in both the pituitary and caudate nucleus it is speculated that a dopaminergic mechanism is responsible for their actions on the enkephalin system. PMID- 2581196 TI - Studies on the mechanism of chlordecone-induced tremor in rats. AB - Organochlorine insecticides such as DDT and chlordecone produce tremor in exposed individuals. Using a spectral analysis technique, chlordecone-induced tremor in rats was found to be dose- and time-related and could be distinguished from pharmacological agents (i.e., harmine, oxotremorine, and apomorphine) that produce tremor or stereotypic behavior. Drugs with known pharmacological effects were used to study the possible mechanism of chlordecone-induced tremor. Although no one neurotransmitter system appears necessary for tremor, the serotonergic, gabaergic, and cholinergic systems appear to contribute to chlordecone-induced tremor. The role of the catecholaminergic system is uncertain. Subsequent experiments indicated that supraspinal processes, possibly located in the brain stem, are important contributors to chlordecone-induced tremor. Activation of the cerebellum via the olivocerebellar tract to produce tremor cannot explain chlordecone's tremorgenic effects. PMID- 2581195 TI - Effects of chlordecone on neuroendocrine function of female rats. AB - The effects of chlordecone on reproductive function was examined in adult females. Chlordecone was shown to mimic estrogen by producing persistent vaginal estrus in ovariectomized and intact females. In ovariectomized females, chlordecone reduced serum levels of luteinizing hormone (LH) and increased prolactin (PRL). In intact females, chlordecone reduced the preovulatory surges of both LH and PRL but had no effect on serum hormones of diestrous females. Chlordecone failed to mimic estrogen in priming the ovariectomized female for behavioral receptivity, and instead appeared to antagonize the priming action of estrogen. Examination of neurotransmitter changes suggested that chlordecone disrupted the usual sequence of events occurring throughout the female's estrous cycle and that this disturbance of neurotransmitter equilibrium contributed to the reproductive dysfunction. The hypothesis that chlordecone disrupts reproductive function by acting as a weak estrogen received considerable support. However, the results of several studies indicated that the neural effects of chlordecone and estradiol were not identical. We have proposed that chlordecone mimics many of the estrogen-receptor mediated neural events. However, because of the persistence of chlordecone in the organism, chlordecone fails to initiate the sequential changes which characterize estrous cyclicity. PMID- 2581197 TI - Neurological manifestations in humans exposed to chlordecone: follow-up results. AB - Twenty-three workers chronically exposed to chlordecone developed overt neurologic manifestations. These included postural and intention tremor, gait difficulty and opsoclonus. Blood levels of chlordecone ranged from 2.0 to 33.0 ppm. The manifestations slowly cleared in all but one worker. PMID- 2581198 TI - Amylase in serous ovarian neoplasms. PMID- 2581199 TI - Characteristics and chemotherapeutic sensitivity of a human testicular cancer grown in artificially immunosuppressed mice. AB - Seven human testicular tumors were transplanted into artificially immunosuppressed mice. Two of them grew progressively (TT2 and TT6) and a serially transplantable line was developed from TT2. The xenografts maintained only the embryonal carcinoma components of originally mixed (embryonal cell carcinoma and choriocarcinoma) donor tumor. Although the histology did not change remarkably with passages, the xenografts lost their capacity to express human choriogonadotropin and alpha-fetoprotein. The latency period shortened, the growth rate remained similar with subsequent transplantations. The tumor cells of the TT2 line presented the human character according to chromosome analysis and were built up of two subsets of cells with a different DNA index estimated by flow cytometry. The embryonal cell carcinoma line was highly sensitive to CY and cisDDP. PVB combination was also effective, although the tumor growth inhibition proved to be only temporary. PMID- 2581200 TI - Histological staining by tritiated actinomycin D: a useful tool to study neoplastic cell heterogeneity and estrogen sensitivity of mammary tumors. AB - The MXT mouse transplantable mammary cancer is characterized by significant amounts of steroid hormone receptors. Moreover this model, as other solid tumors, contains diverse subpopulations of neoplastic cells. In the present study we have examined this pattern as well as the influence of exogenous physiologic doses of estradiol on tumor cell subpopulations. Their identification was undertaken at the morphological level employing incubation of tritiated actinomycin D with fixed material followed by autoradiography. This semiquantitative cytochemical method has proved itself to be a useful tool in order to assess the cellular heterogeneity of carcinoma cells. PMID- 2581202 TI - Combination chemotherapy prior to definitive local therapy in squamous cell carcinoma of the head and neck. AB - 30 patients with locally advanced squamous cell carcinoma of the head and neck were given chemotherapy with methotrexate, bleomycin and cis-Platinum prior to planned definitive surgery and/or radiation therapy. Chemotherapy was well tolerated and 90% of patients responded. Of 14 initially unresectable patients, 6 became operable after chemotherapy. After definitive therapy 70% of patients were considered complete responders, and 43% of the entire cohort remain disease-free. All partial responders have died. Patients receiving chemotherapy, surgery and radiation had a significantly greater likelihood of achieving a complete response than those receiving chemotherapy and radiation alone. Although this initial chemotherapy is highly active in this disease its contribution to ultimate survival is unclear. Overall treatment success is determined by the results of definitive therapy. PMID- 2581201 TI - Efficacy of large-volume plasma exchange in patients with chemotherapy-resistant metastatic colorectal cancer. AB - 23 patients with advanced metastatic colorectal adenocarcinoma and measurable metastases were treated with chemotherapy until resistance to chemotherapy was evident. Chemotherapy was then not discontinued but administered for at least a further cycle combined with large-volume plasma exchange (PE). 15 of 23 patients responded again for 4-45 weeks, an average of 13. This effect was thought to be due to dilution or elimination of serum-blocking factors, which could be measured by mixed lymphocyte culture (MLC) assay. 16 of 20 patients showed a positive correlation between the clinical course and MLC activity, if the basic MLC reactivity was compared with the MLC levels at the start of each subsequent PE in each patient. It is postulated that in some tumors there is a resistance to chemotherapy mediated by plasma-blocking factors. PMID- 2581203 TI - [Immunochemical approach to the identification of specific markers of the corneal epithelium in Rana temporaria]. AB - Biochemical and immunochemical studies of water soluble proteins in the corneal epithelium (CE) of adult frogs were carried out. Up to 30-40 protein fractions were found in the CE extracts using the methods of isoelectrofocusing and electrophoresis with SDS. The major part of the CE proteins is in the acid zone (pH 4.2-6.2) and is presented by three peptide fractions in the molecular weight range of 40-50 kD. The CE peptide spectrum is most close to that of epidermis and differs markedly from that of lens fibers. Up to 20 water-soluble antigens were revealed by rabbit antisera against the total extract, among them 10 antigens are immunologically similar with the blood serum proteins. Out of 10 tissue antigens, 6 are interorganic. Only two corneal antigens were not found in epidermis. One of them was found only in CE, retina and lens epithelium. Another antigen is present in considerable quantities only in liver, heart and lung. The synthesis of most tissue specific antigens and antigens immunologically similar with alpha- and beta-crystallins of R. temporaria was shown in CE by immunoautoradiography. The antigenic composition proved to be similar in CE, epidermis and lens epithelium. PMID- 2581204 TI - Fluorescein angiography of soft contact lens induced vascularization in penetrating keratoplasty. AB - Soft contact lenses after penetrating keratoplasty have become more popular as improved materials with high water content and high oxygen permeability have become available. However, aphakic patients who have undergone penetrating keratoplasty seem to be at high risk for development of graft vascularization when extended wear soft lenses are used for optical correction. This report, to our knowledge, is the first to use corneal fluorescein angiography to study contact lens induced vascularization. Corneal fluorescein angiography, in two cases, showed that vascularization was often more extensive than clinically apparent. Further, these "new" vessels, in both cases, were shown to be "leaky." This great degree of leak contributed to graft edema in both and possibly, in one case, to graft rejection. These findings suggest that care in fitting and careful follow-up is necessary in any graft patient fit with an extended wear lens and that delicate or problem patients may be better aided with other forms of optical correction. Further, this report shows the value of corneal fluorescein angiography as a useful tool in the study of vascularization of the cornea from any cause. PMID- 2581205 TI - Postoperative subretinal neovascular membrane at the drain site of a scleral buckle. AB - A 57-year-old patient underwent a scleral buckle operation for a rhegmatogenous bullous retinal detachment. An episcleral buckle and cryotherapy were used. Drainage of subretinal fluid was performed beneath the buckle as well as posterior to the buckle, close to the posterior pole. The postoperative course was unremarkable. Eight months later, the patient developed a subretinal neovascular membrane at the drain site posterior to the buckle. This was documented by fluorescein angiography. Such membranes have not been previously documented at retinal drain sites in an ophthalmic journal. PMID- 2581206 TI - Cryotherapy for retinopathy of prematurity. A personal retrospective. AB - Six patients from 1975 to 1981 were treated by cryotherapy for active retinopathy and prematurity. One eye was treated, leaving the second eye as a control. Cryotherapy was applied just posterior to the demarcation line, under direct observation and utilizing the cataract probe. Conclusions from this experience are that in order to be effective, cryotherapy must be performed comparatively early in Stage III. Unfortunately, this would lead to treatment of many cases that would spontaneously regress. Treatment of late Stage III, rapidly progressive cases is not impressive. PMID- 2581207 TI - The treatment of advanced retinopathy of prematurity by cryotherapy and scleral buckling surgery. AB - Seventeen eyes of nine extremely premature infants with severe acute proliferative retinopathy of prematurity (ROP, Grades III-V) were treated. Cryotherapy alone was used in ten eyes to ablate extensive areas of avascular retina to thereby induce involution of widespread intravitreous neovascularization. No attempt was made to directly treat the arteriovenous shunt or neovascularization itself. Scleral buckling surgery was used in combination with cryotherapy in seven additional eyes to relieve diffuse vitreous traction to intravitreous neovascularization which had caused extensive traction retinal detachment. Cryotherapy was uniformly successful in causing involution of widespread intravitreous neovascularization in all patients treated. Scleral buckling surgery was initially effective in reattaching the retina in all cases but late manifestations of severe ongoing vitreoretinal traction required additional open-sky vitrectomy in two eyes and resulted in inoperable recurrent total traction retinal detachment in one eye and extensive macular scarring in another. A comparison is made between the proliferative retinopathies seen in ROP and diabetes mellitus and a rationale for effective cryotherapy in ROP is presented. In our clinical experience, the single most important prognostic factor determining the potential severity of ROP is the width and extent of the retinal avascular zone. The wider the zone, the greater the probability of rapid progression from early to advanced grades of disease. PMID- 2581208 TI - The effect of thermal mode Nd:YAG laser radiation on vessels and ocular tissues. Experimental and clinical findings. AB - Ultrastructural examination of mesenteric vessels of pigmented rabbits after irradiation with the thermal mode of Nd:YAG laser showed an excellent hemostatic effect. Clinical experience parallels those findings. PMID- 2581209 TI - [Management of Leriche syndrome by Dotter's method and oral fibrinolytic agents]. PMID- 2581210 TI - [Serum alpha fetoprotein patterns in the newborn with indirect hyperbilirubinemia]. PMID- 2581211 TI - Analysis of complete responders after initial treatment with chemotherapy in head and neck cancer. AB - We treated 60 patients with cisplatin-based combination chemotherapy before definitive surgery and/or radiation. All had squamous cell tumors of the head and neck, stages II to IV, M0. Twelve patients (20%) achieved a complete remission after chemotherapy. Eight of these patients showed no histologic evidence of residual disease after biopsy or surgery. Definitive local therapy with surgery and/or radiation was carried out on almost all patients regardless of the extent of the response to preceding chemotherapy. Chemotherapy-induced complete responders have had an improved survival rate in comparison with patients achieving a partial response or less. The extent of primary tumor correlates inversely with a complete response to chemotherapy. PMID- 2581213 TI - Immunoperoxidase staining in the diagnosis of malignant tumors of the head and neck. PMID- 2581212 TI - Endoscopic treatment of tracheobronchial malignancy. Experience with Nd-YAG and CO2 lasers in 506 operations. AB - Laser technology and the endoscope have been combined for the palliation of obstructive tracheobronchial malignant lesions. The neodymium-yttrium-aluminum garnet (Nd-YAG) laser was used to treat 249 patients (447 operations), and the CO2 laser was used on 34 patients (59 operations). Hemorrhage, the major complication in both groups of patients, was more easily controlled with the Nd YAG laser. One patient in the CO2 laser group died, and one patient in the group being treated with Nd-YAG laser bronchoscopy died. The Nd-YAG laser can be applied more efficiently through a fiber system, with better optic control and secure hemostasis. The commonest indications for treatment were dyspnea, obstructive pneumonia, and hemoptysis. Extrinsic compression was the most frequent reason for failure. The Nd-YAG laser, most often applied through open rigid bronchoscopes under general anesthesia, has become our treatment of choice for the palliation of tracheobronchial malignancy. PMID- 2581214 TI - [Risk concept in perinatal and pediatric medicine with reference to aspects of developmental theory. 1. Risk concepts in perinatal and pediatric medicine]. PMID- 2581215 TI - [Risk concept in perinatal and pediatric medicine with reference to aspects of developmental theory. 2. Risk concepts and developmental-theoretical positions]. PMID- 2581216 TI - Antigenicity and immunogenicity of the tegumental outer membrane of adult Schistosoma mansoni. AB - The tegumental membranes of adult Schistosoma mansoni have been isolated and purified and shown to function as potent immunogens; they elicit an essentially identical immune response in rabbits, rats and mice. Anti-membrane antisera harvested from these animals consistently recognized common antigens, of relative molecular weight (mol. wt) 32 000 and 20 000, on the surface of young schistosomula, 5 day old lung worms and adult worm purified membranes. An additional molecule of 25 000 mol. wt was present on the surface of lung worms and adult worm membranes and was specifically recognised by serum from chronically infected mice and by serum from rabbits inoculated with adult worm purified membranes. The concept of antigenic identity between developmental stages that parasitize the mammalian host was further substantiated by the observation that anti-membrane antiserum bound to live schistosomula, lung worms and adult parasites as measured by indirect immunofluorescence. In complement mediated in vitro cytotoxicity assays, the sera from rabbits inoculated with either adult worm purified membranes, or the 32 000 mol. wt antigen partially purified from adult worm membranes, mediated levels of schistosomula killing as high as those obtained with sera from chronically infected mice. These rabbit antisera also promoted eosinophil adherence and killing of newly transformed schistosomula, but lung stage parasites, despite binding the anti-membrane antiserum, were refractory to both humoral and cellular cytotoxicity. The significance of antigenic identity is discussed in relation to the concept of concomitant immunity. PMID- 2581217 TI - Microscopic differential diagnosis of small acinar adenocarcinoma of prostate. PMID- 2581218 TI - One-micron plastic sections of human peripheral blood and bone marrow specimens and peroxidase cytochemistry: use in the differential diagnosis of acute leukemias. AB - Peripheral blood or bone marrow samples from 142 patients with hematologic disorders were prepared for light microscopic study using 1-micron plastic sections. The same methodology provided excellent material for ultrastructural study of the same samples. Sixty-one of these cases were studied by electron microscopy and have been reported elsewhere. The techniques employed allowed the study of peripheral blood, a specimen generated by a relatively noninvasive procedure. The methods used provided light or electron microscopic identification of glycogen or peroxidase. These methods provided rapid results. Both light microscopic results and electron microscopic data were available within the same time frame as were routine paraffin sections. Preparation of plastic sections for light microscopy makes use of simple, well-known techniques and uses inexpensive manual microtomes. These methods are, therefore, accessible to any routine histopathology laboratory. The same material (blocks) can then be submitted to any diagnostic electron microscopic laboratory for further analysis if necessary. The extra resolution afforded by use of thin plastic sections for light microscopy allows easy identification of cell types. We have found these methods useful in the accurate classification of many acute leukemias and suggest that such improvement in diagnosis should be made available to physicians concerned with the diagnosis and care of patients with hematologic disorders. PMID- 2581219 TI - Serous surface papillary carcinoma of the ovary: a clinical, pathologic, ultrastructural, and immunohistochemical study of 11 cases. PMID- 2581220 TI - A note on interdisciplinary research in developmental/behavioral pediatrics/psychology. AB - In sum, we have offered a few observations about the practice of interdisciplinary research. Now, in addition to our rather specific suggestions, we want to add a few general comments about the interactions of professionals who are actually involved in interdisciplinary research. Collaboration between physicians and psychologists can be enriching, stimulating, and rewarding. But it can also be problematic, because the former do not have much exposure to research and the latter do not have much exposure to clinical issues. Bringing these skills together may require many hours of discussion and reading each other's publications. Overall, physicians need to improve their research skills. Reading statistics texts, taking courses, handling data sets, reviewing other researchers' statistical designs are all reasonable strategies. Psychologists also need to expand their knowledge base. Reading the clinical literature is a start, but this ought to be supplemented by consistent exposure to the clinical milieu. The physician, who has access to the clinical milieu, needs to be sensitive to the question of exposure. Our final comments about collaboration are perhaps the most sensitive ones. The maintenance of a solid physician and psychologist research collaboration requires thoughtfulness, understanding, tact, and nurturance. Consider the status and responsibilities of the physician. He or she often outranks the psychologist, has access to the subject population, daily confronts ethical issues surrounding patient diagnoses, and controls communication of information to child and family. A sense of being in charge develops. Consequently, the psychologist may be perceived as being an adjunct to the research, responsible for day-to-day operations and committing ideas to paper.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581221 TI - Effect of changes in oxygen tension on vascular and platelet hydroxyacid metabolites. II. Hypoxia increases 15-hydroxyeicosatetraenoic acid, a proangiogenic metabolite. AB - Current strict O2 management may be precipitating more severe retinopathy of prematurity than would occur with a more lenient approach. Hypoxemia in an animal model has also been found to worsen retinal neovascularization. It has recently been shown that the hydroxyeicosatetraenoic acids can modulate angiogenesis. 15 Hydroxyeicosatetraenoic acid is proangiogenic, whereas 12-hydroxyeicosatetraenoic acid is an antiangiogenic metabolite. In vitro exposure of paired human neonatal vessels (n = 7) to hypoxia enhanced the production of total vascular hydroxyacids (232 +/- 36 pmol/mg of protein [experimental group] nu 168 +/- 31 pmol [control group]; P less than .01). The increase in vascular 15-hydroxyeicosatetraenoic acid under hypoxic conditions was even more significant (P less than .001). However, platelet production of 12-hydroxyeicosatetraenoic acid was not significantly affected by hypoxia. These observations suggest a possible biochemical basis for the abnormal angiogenic process that occurs during the proliferation phase of the retinopathy of prematurity. The production of local hydroxyeicosatetraenoic acids in tissues manifesting abnormal neovascularization needs to be further evaluated. PMID- 2581222 TI - [Reserpine in the treatment of disorders of cardiac rhythm in children]. PMID- 2581224 TI - Identification of a voltage-dependent anion channel in the apical membrane of a Cl(-)-secretory epithelium (MDCK). AB - An anion-selective channel of large unit conductance is present in apical membranes of a secretory epithelial cell. For cell-attached patch-clamp configuration on cultured MDCK cells channels with a conductance of about 460 pS are observed at 37 degrees C. The channel becomes spontaneously activated only in rare cases. In inside-out membrane patches the probability of observing this type of channel increased significantly suggesting that the channel is controlled by an up to now unknown mechanism. The channel shows a voltage-dependent burst kinetic. PMID- 2581225 TI - Muscarinic receptor-mediated increase of intracellular Na+-ion activity and force of contraction. AB - The aim of the present study was to determine the mechanism of the positive inotropic effect of carbachol on ventricular myocardium. Carbachol produced a concentration-dependent (0.1 to 300 mumol/l) increase in contraction force on the catecholamine-depleted papillary muscle of the guinea pig without affecting the normal action potential or the slow action potential evoked in 24 mmol/l K+. Since atropine prevented the inotropic effect of carbachol, muscarinic receptors were involved. Carbachol (300 mumol/l) produced an increase in intracellular Na+ ion-activity, aiNa, by about 3 mmol/l in the quiescent muscle, and the time course of the aiNa change corresponded with the development of the positive inotropic effect as determined in the stimulated preparation (0.2 Hz). The effect of carbachol on force of contraction and on aiNa was diminished by reducing [Ca2+]0. The positive inotropic effect of carbachol was dependent on repetitive activity and was markedly enhanced in the presence of dihydro-ouabain. The results are consistent with the hypothesis, that carbachol increases the Na+ permeability of the sarcolemma via muscarinic receptors, and enhances force of contraction by stimulating the Na+-Ca2+-exchange. PMID- 2581226 TI - [Medical treatment of severe pain]. PMID- 2581227 TI - [The terminal cancer patient]. PMID- 2581223 TI - Aldosterone does not stimulate the Na:K pump in isolated turtle colon. AB - The study of the mechanisms by which mineralocorticoids stimulate sodium absorption across distal epithelia has focused on three possible sites of action: apical sodium permeability, the basolateral Na:K pump, and the production of high energy substrates. Recently we developed a method for direct measurement of the current generated by the basolateral Na:K pump of the turtle colon [15]. In the presence of mucosal amphotericin-B and serosal barium the short-circuit current across the colon can be equated with the current produced by active electrogenic exchange of sodium for potassium across the basolateral membrane. This pump current is a measure of the transport capacity of the epithelial Na:K pump that is uncomplicated by changes in apical membrane sodium permeability. Pump currents, thus defined, were compared in control tissues and tissues treated with aldosterone in vitro. After 9 h Na absorption was increased 4-fold in the aldosterone-treated tissues but the values of the pump current were identical in the two groups. This result indicates that acute stimulation of sodium absorption by aldosterone does not occur by stimulating the Na:K pump directly. PMID- 2581228 TI - [Lars Terenius about neuropeptides and pain: Endorphines alleviate stress--a curative effect? A new spinal-active analgesic insight. Interview by Birgit Lindell]. PMID- 2581229 TI - Health education. Projecting the facts. PMID- 2581230 TI - Clinical. A new approach to combat viruses. PMID- 2581231 TI - Characterization of the histamine releasing effect of neurotensin in the rat heart. AB - Bolus injections of neurotensin (NT) in the rat perfused heart elicited a transient, dose-dependent histamine release. The histamine releasing effect of NT appears to be independent of the heart rate and coronary perfusion pressure and it was not influenced by atropine, propanolol, prazosin, methysergide, ketanserin, indomethacin, morphine, lidocaine or by removal of the atria. However, it was potentiated by adenosine, inhibited by sub-stimulatory concentrations of NT and the mast cell membrane stabilizing drug cromoglycate but was unaltered by the calcium antagonist verapamil. The absence of calcium in the heart perfusate suppressed the histamine releasing effect of NT. These results suggest that the histamine releasing effect of NT in the rat heart results from a direct effect on ventricular mast cells and is calcium-dependent. PMID- 2581232 TI - Cardiovascular interactions between methionine-enkephalin and substance P in the conscious dog. AB - Interactions between the undecapeptide Substance P (SP) and the pentapeptide methionine-enkephalin (Met5-ENK) have been described in isolated organ systems and in baroreceptor reflex mechanisms. Previous studies in our laboratory have demonstrated that systemically injected Met5-ENK simultaneously increases mean systemic arterial pressure (MAP) and heart rate (HR) in the conscious, chronically instrumented dog. We have now evaluated cardiovascular interactions between SP and Met5-ENK. In this model, SP injected intravenously produces a rapid and transient decrease in MAP and increase in HR over the dose range from 1.0 to 10.0 ng/kg. SP does not appear to appreciably alter subsequent responses to Met5-ENK. At SP doses of 1.0 ng/kg, the peak hemodynamic response to SP and Met5-ENK (35 micrograms/kg) given together appears to represent a simple summation effect of both drugs on HR and MAP. However, at higher SP doses (5.0 ng/kg), the SP response predominates and is little altered by the presence of Met5-ENK. Thus, Met5-ENK does appear capable of modulating the hemodynamic responses to SP over certain dose ranges. PMID- 2581233 TI - Effects of MET-ENK, substance P and SRIF on the behavior of Hemichromis bimaculatus. AB - Administration of 10 and 30 micrograms methionine-enkephalin (MET-ENK)/g bw (n = 10/dose) affected the propensity towards fighting in H. bimaculatus; 10 micrograms increased, while 30 micrograms decreased the aggressive behavior. MET ENK also affected a number of behavior patterns displayed by the fish. Moreover, the "wet-dog-shakes" observed suggest that MET-ENK acts on opiate-receptors. Treatment with substance P (SP)/g bw (n = 10/dose) induced chafing movements in the fish slightly. It also decreased fighting and increased biting of the air stone, which is evidence that H. bimaculatus is still aggressive, directing its attacks to different objects. When 4, 8, 12 micrograms somatostatin (SRIF)/g bw (n = 10/dose) were injected, H. bimaculatus stopped fighting for several hours after the onset of treatment, depending on the dosage. Somatostatin reduces blood glucose concentration, causing a sudden stop of aggressive behavior, 0.04, 0.1, 0.6, 1.0 and 3.0 IU prolactin (PRL)/g bw (n = 5/dose) eventually decreased fighting and affected a number of behavior patterns displayed by the fish. PMID- 2581234 TI - Inhibition of androgen metabolism in stroma and epithelium of the human benign prostatic hyperplasia by progesterone, estrone, and estradiol. AB - It has been shown that progesterone, estrone, and estradiol are present in significant amounts in the human benign prostatic hyperplasia (BPH). Therefore it was of interest to determine the inhibitory effect of these steroids on the 5 alpha-reductase and 3 alpha (beta)-hydroxysteroiddehydrogenase (HSDH) activities, the enzymes responsible for the conversion of testosterone to 5 alpha dihydrotestosterone (DHT), and DHT to 3 alpha (beta)-androstanediols, respectively. The enzyme inhibition was analyzed in vitro by measuring the 5 alpha-reductase in the presence of either progesterone, estrone, or estradiol, using testosterone as substrate. The DHT was used as substrate for HSDH. The metabolites were quantified by t.l.c. The main results were as follows: (1) Concerning 5 alpha-reductase in BPH, the mean inhibitor constants (KI; microM) of progesterone, estrone, and estradiol were 0.11, 15.5, and 5.1, respectively. (2) Analyzing epithelium and stroma of BPH separately, the inhibition of 5 alpha reductase resulted in nearly identical KI's. (3) Concerning HSDH in BPH, the mean KI's of progesterone, estrone, and estradiol were 169, 63, and 192, respectively. (4) Analyzing epithelium and stroma of BPH separately, the inhibition of HSDH led to nearly identical KI's. (5) The kinetic parameters (KM, Vmax) of the 5 alpha reduction of progesterone and testosterone were nearly identical. These results led to the suggestion that the endogenous concentrations of progesterone, estrone, and estradiol have no significant inhibitory effect on the 5 alpha reductase and HSDH in vivo. Furthermore, the nearly identical inhibitor constants found for both enzymes in epithelium and stroma of BPH indicate that in both compartments the 5 alpha-reductase and HSDH are qualitatively identical. PMID- 2581235 TI - Tissue interactions and prostatic growth: II. Morphological and biochemical characterization of adult mouse prostatic hyperplasia induced by fetal urogenital sinus implants. AB - Current hypotheses regarding the causes of human benign prostatic hyperplasia have implicated both steroid hormone imbalance and tissue interactions. To examine the role of the latter we have further investigated the phenomenon of urogenital sinus-induced hyperplasia of the adult mouse ventral prostate. Urogenital sinuses (UGS) or purified urogenital mesenchyme (UGM) from C3H mice were implanted into the ventral prostates or coagulating glands of 50- to 90-day old BALB/c-nu/nu hosts. The animals were sacrificed at 15, 30, and 180 days postimplantation to establish time dependence. Wet weight and DNA content were used as measures of net growth. Glucose phosphate isomerase (GPI) isozyme analysis was used to determine the relative contributions of C3H and BALB/c cells to the enlarged chimeric ventral prostates. It was determined that the induced growth is time-dependent and that the UGS induces 2- to 4-fold more growth than UGM. GPI analysis shows that UGM-induced growth was composed primarily of host derived cells whereas the UGS is composed nearly equally of host- and implant derived cells. Histologic analysis reveals that the UGS implants induce marked epithelial proliferation. The proliferating glands occur in clusters, and the epithelium within the glands appears cribriform. Foci of postobstructive cystic atrophy are also found. Remnants of the implanted UGS are still present even at 180 days postimplantation. UGM-induced growth is of a more subtle nature and appears morphologically similar to the sham-operated controls. In view of the morphologic similarity with human disease, as well as the time and hormonal dependence of UGS-induced ventral prostatic hyperplasia, this model represents the basis for a unified hypothesis regarding the roles of tissue interaction and hormonal milieu in human benign prostatic hyperplasia. PMID- 2581236 TI - Sex steroid receptors in normal and hyperplastic human prostate. AB - The concentrations of sex steroid receptors (per unit DNA) were measured in normal periurethral and peripheral prostatic tissue samples from seven men (mean age 64 years; range 54-71 years) undergoing cystectomy for bladder cancer, and in hyperplastic nodules from 15 men with BPH (mean age 69 years; range 60-89). Occupied androgen (AR) and estrogen (ER) receptors were measured with an improved exchange procedure, where receptor-binding sites were stabilized by a combinatorial procedure involving careful washout of extracellular secretory products (including proteases) prior to homogenization, inclusion of 0.5 mM phenylmethyl sulfonylfluoride (PMSF) and 20 mM molybdate in the exchange medium, and long-term incubation at 0-4 degrees C. Bound radioligands were separated by a hydroxylapatite (HAP) batch adsorption procedure. Maximal specific exchange binding of 3H-R 1881 or 3H-estradiol in total homogenates of human prostate samples was achieved after incubation periods of about 72 h at 0-4 degrees C. In contrast, progestin receptors (PR) were readily available for binding 3H-R 5020; thus overnight binding at 0-4 degrees C was routinely used to measure PR. Binding specificities and equilibrium binding constants (calculated from 8-point Scatchard plots, correcting for nonsaturable binding) were found to be characteristic for AR, PR, and ER, respectively. The receptor results obtained in this study demonstrate that no significant differences existed in total AR per unit DNA between hyperplastic and either central or peripheral prostatic tissue samples; PR was present in both zones of normal prostatic tissue as often as in BPH samples, with PR concentrations significantly lower in hyperplastic samples; and ER was irregularly detected in both normal and hyperplastic tissue in low concentration relative to AR and PR; the frequency of ER detection was much lower in BPH than in normal prostate tissue. Studies of steroid receptor content relative to enzyme markers specific for epithelial and stromal cells in BPH samples showed a positive correlation between acid phosphatase activity (a specific marker for epithelial cells) and both AR and PR. No correlation was observed between AR or PR with either prolyl hydroxylase or myosin ATPase (specific markers for stromal cells). These observations suggest that PR, as well as AR, is primarily associated with the epithelial elements of prostate. Because of the relative infrequency of ER, similar correlation of ER with enzyme markers was not possible. PMID- 2581237 TI - Qualitative analysis of Coomassie-blue-stained proteins from normal prostate, benign prostatic hypertrophy, or adenocarcinoma of the prostate, separated by two dimensional protein electrophoresis. AB - Samples from nine normal prostates (N), ten benign hypertrophic prostates (BPH), and eight adenocarcinomas of the prostate (ACP), obtained from the National Prostatic Cancer Project were analyzed by two-dimensional (2D)-protein electrophoresis. Qualitative analysis of Coomassie-blue-stained acidic proteins between pI 3.5 and 6.8 yielded these results: The total number of enumerated proteins was 136 (N), 107 (BPH), and 147 (ACP). Ninety-two denoted proteins were deemed common to the three kinds of samples, three were considered present in N and BPH, 7 in BPH and ACP, and 28 in N and ACP. Thirteen, five, and 20 proteins were detected only in N, BPH, or ACP. These proteins cannot be considered "unique" to their respective samples, since amounts of protein that do not exceed the minimum sensitivity of the dye may be present in the other samples. The similarity in the patterns of proteins from these three types of prostate samples is consistent with the following hypothesis: The distribution of proteins from histologically ambiguous prostate samples will correlate more closely with these protein profiles than with those associated with cancers originating from other organs. PMID- 2581238 TI - Developmental disorders. When to refer a child to a specialized center. AB - Primary care physicians need to be informed about and attuned to developmental problems in children. Developmental disorders present in infancy and childhood with characteristic symptoms that should alert the physician to the need for in depth evaluation. This type of assessement can best be carried out in a medically based, multidisciplinary center with a team of professionals who act as consultants to and partners with the physician in caring for the child and family. PMID- 2581239 TI - Growth and protein turnover in the skeletal muscles of broiler chicks. AB - Growth and protein turnover were examined in the breast (pectoralis thoracica) and the leg (gastrocnemius-peroneus) muscles of broiler chicks at 1, 2, 4, and 6 weeks posthatching. The fractional rate of protein synthesis (ks) was measured by an isotope emulsion method. The fractional degradation rate (kd) was calculated from the difference in ks and fractional deposition rate (kg), which was estimated from regression equations of muscle size and protein content on body weights. The growth rate (%/day) of skeletal muscle exceeded that of the whole body. Muscle growth involved an increase in the total deoxyribonucleic acid (DNA) and the DNA-unit size and a subsequent decrease in the concentrations of nucleic acids without alteration in the ribonucleic acid (RNA):DNA ratio and RNA and DNA activity. The ks in breast muscle protein fell markedly from 48 to 16%/day between 1 and 6 weeks posthatching, whereas in leg muscle, ks underwent a more gradual decrease; from 36 to 17%/day during the same period. These changes resulted mainly from the reduction of DNA and RNA concentrations with age. The kd decreased only slightly between 1 and 2 weeks in the both muscle groups. The kg also showed a developmental fall from 33 to 4%/day and from 21 to 4%/day in the breast and leg muscles, respectively, during the 5-week period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581240 TI - Characteristics of growth and protein turnover in skeletal muscle of turkey poults. AB - Protein turnover and DNA and RNA levels were measured in the breast (pectoralis thoracica) and leg (gastrocnemius-peroneus) muscles of large white (Nicholas strain) turkey poults from 1 to 8 weeks of age to investigate their cellular growth and to evaluate the influence of protein turnover on muscle growth. Fractional rates of protein deposition (kg) were determined from regression equations of muscle size and protein content on body weights. Protein synthesis rates (ks) were measured by an isotope emulsion technique. Protein degradation rates (kd) were estimated by the difference between ks and kg. Muscle growth involved increases in total deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), an increase in the DNA-unit size, and decreases in concentrations of the nucleic acids without changes in the RNA:DNA ratio or RNA and DNA activity. The muscles showed developmental changes in ks from 56 to 10%/day and from 38 to 13%/day in breast and leg, respectively, over the 7-week period. The fractional degradation rate also fell from 22 to 7%/day in the breast muscle and from 21 to 10%/day in the leg muscle. The disproportionate decline of ks and kd resulted in an age-associated fall in kg from 34 to 4%/day and from 18 to 3%/day in the breast and the leg muscles, respectively. The efficiency of protein deposition decreased from 61 to 35% in breast muscle and 46 to 20% in leg muscle. The results were qualitatively similar to those obtained in a study with broiler chicks. PMID- 2581241 TI - Prednisolone in terminal breast and bronchogenic cancer. PMID- 2581242 TI - Prenatal diagnosis of cystic fibrosis. I. Prospective study of 51 pregnancies. AB - A prenatal diagnosis was performed in 51 pregnancies with a 1-in-4 risk of having a child with cystic fibrosis. The criteria for determining an affected fetus were based on the results of alkaline phosphatase (ALP) residual activity after inhibition by phenylalanine and by homoarginine, of total ALP activity, and of gamma-glutamyltranspeptidase (GGTP) activity in the amniotic fluid taken between 16 and 19 weeks of pregnancy. The chromosomal analysis of amniotic fluid cells showed trisomy 13 in one case which was excluded from the analysis of biochemical assays. The biochemical assays were in the normal ranges in the amniotic fluid of 35 pregnancies: 26 have reached term and a normal infant has been born, 9 are still in progress. A deficiency of the ALP phenylalanine-inhibitable form, depressed values of total ALP and GGTP were observed in the amniotic fluid of 15 pregnancies: one pregnancy went to term and the infant had CF, in 14 cases the pregnancy was terminated, and meconium ileus was observed in ten of these cases. It was observed that the changes towards abnormal values became more significant with advancing gestational age and that 18 weeks appeared to be the optimum time for diagnostic amniocentesis. PMID- 2581243 TI - Glycosylated proteins in diabetic nephropathy. AB - This study was carried out on 55 diabetic patients, 20 of whom had diabetic nephropathy, and 10 controls. Glycosylated haemoglobin, glycosylated serum protein, glucoprotein, serum protein electrophoresis, blood urea, serum creatinine and beta 2-microglobulin were measured. A significant increase of glucoprotein was observed in patients with diabetic nephropathy. No correlation was found between glycosylated serum protein and glycosylated haemoglobin and duration of diabetes. Glycosylated serum protein showed a positive correlation with beta 2-microglobulin, indicating a link between renal involvement and the rise in glycosylated serum protein. Whether there is a pathogenic relation between glycosylated serum protein and the development of nephropathy awaits further evidence. PMID- 2581244 TI - Characterization of the ColE1 primer-RNA1 complex: analysis of a domain of ColE1 RNA1 necessary for its interaction with primer RNA. AB - RNA1 is a small, plasmid-encoded transcript involved in the replication control of the plasmid ColE1. RNA1 blocks replication by preventing processing of the primer RNA necessary for the initiation of replication. It has been proposed that inhibition by RNA1 involves a direct interaction between RNA1 and primer RNA. Here we describe an in vitro system that allows the detection and characterization of the RNA1-primer complex. Using this system, we have demonstrated that the association between ColE1 RNA1 and primer results in the formation of an RNA X RNA hybrid between RNA1 and the 5' end of primer RNA. Furthermore, analysis of mutant RNA1 molecules containing sequence alterations in the 5' single-stranded region of the molecule has revealed that this portion of RNA1 is necessary for the formation of the RNA1-primer complex. These experiments indicate that, in addition to the three single-stranded loops of RNA1, the 5' single-stranded region is a functional domain of the molecule. PMID- 2581245 TI - Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus. AB - Six alpha 2-macroglobulin (alpha 2M) cDNA clones were isolated from a human liver cDNA library by using synthetic oligonucleotides as hybridization probes. One of these, p alpha 2M1, carries a 4.6 kilobase-pair insert, which was sequenced. The insert contains the coding sequences for the mature alpha 2M polypeptide (1451 amino acids) and for a 23-amino acid signal peptide at the NH2 terminus of the precursor pro-alpha 2M. At the 3' end of the insert a poly(A) addition signal A-A T-A-A-A and part of the poly(A) tail of the messenger RNA were found. The protein sequence deduced from the nucleotide sequence agrees with the published alpha 2M amino acid sequence for all except three residues. The alpha 2M locus was assigned to human chromosome 12 by Southern blot analysis with DNA from a panel of mouse/human somatic cell hybrids, using alpha 2M cDNA as a hybridization probe. PMID- 2581246 TI - Ionic responses rapidly elicited by activation of protein kinase C in quiescent Swiss 3T3 cells. AB - Diacylglycerol and phorbol esters activate protein kinase C in intact cells. We report here that addition of the synthetic diacylglycerol 1-oleoyl-2 acetylglycerol (OAG) to quiescent cultures of Swiss 3T3 cells caused a marked increase in the rate of ouabain-sensitive 86Rb+ uptake, a measure of the activity of the Na+/K+ pump. The effect was dose-dependent and could be detected after 1 min of exposure to the diacylglycerol. OAG stimulated Na+ influx via an amiloride sensitive pathway and increased intracellular pH by 0.15 pH unit. Phorbol 12,13 dibutyrate (PBt2) also enhanced ouabain-sensitive 86Rb+ uptake and amiloride sensitive 22Na+ influx. Prolonged treatment (40 hr) of 3T3 cells with PBt2 at a saturating dose, which reduces the number of PBt2 binding sites and protein kinase C activity, abolished the ionic response of the cells to a subsequent addition of either OAG or PBt2. Appropriate controls using acid "loads" and the Na+ ionophore monensin showed that the function of the Na+/H+ antiport system and of the Na+/K+ pump was not impaired in the PBt2-desensitized cells. We suggest that activation of protein kinase C elicits, either directly or indirectly, enhanced Na+/H+ antiport activity, which, in turn, leads to Na+ influx, intracellular pH modulation, and stimulation of the Na+/K+ pump. PMID- 2581247 TI - Mouse major histocompatibility class I gene expression begins at midsomite stage and is inducible in earlier-stage embryos by interferon. AB - To determine the timing of major histocompatibility complex class I gene expression during embryonic development, binding of anti-class I antibodies and appearance of class I gene transcripts were examined in mouse embryos from the egg-cylinder stage through day 16 of gestation. By using two series of monoclonal antibodies reactive with monomorphic and polymorphic determinants of class I antigens, it was found that cell-surface expression of the antigens becomes detectable at a low level only after midsomite stage on gestation day 10, at a time when embryos are developed beyond primordial organogenesis and have partial blood circulation. In agreement with the above finding, a low level of class I mRNA became detectable in day 9 and older embryos in blot hybridization. The level of class I transcripts in embryos at least to day 13 remained less than 1/50th that in adult spleen cells. Cells from head-fold stage embryos (gestation day 8), which otherwise do not have an appreciable amount of class I mRNA or surface antigens, begin to express a high level of antigens upon treatment with mouse alpha/beta or gamma interferon. This induction of class I antigen expression appears to be stage specific in that embryos in an earlier egg cylinder stage (day 6) failed to express the antigens after interferon treatment. A possible role of interferons in activating class I genes during in vivo embryonic development is suggested. PMID- 2581248 TI - Phosphorylation of the calcium antagonist receptor of the voltage-sensitive calcium channel by cAMP-dependent protein kinase. AB - Physiological studies indicate that voltage-sensitive calcium channels are regulated by cAMP and protein phosphorylation. The calcium antagonist receptor of the voltage-sensitive calcium channel from transverse-tubule membranes consists of three subunits, designated alpha, beta, and gamma. The catalytic subunit of cAMP-dependent protein kinase phosphorylates both the alpha and beta subunits of the purified receptor at a rate and extent that suggests they are potential physiological substrates of this enzyme. The phosphorylation of the alpha and beta subunits in transverse-tubule membranes was analyzed by two-dimensional gel electrophoresis. In intact transverse-tubule membranes, the alpha subunit is not significantly phosphorylated. However, the beta subunit, identified by its Mr, pI, and binding to wheat germ agglutinin-Sepharose, was one of the substrates selectively phosphorylated by cAMP-dependent protein kinase in transverse-tubule membranes. These results suggest that cAMP-dependent phosphorylation of the beta subunit of the calcium antagonist receptor may be an important regulatory mechanism for calcium channel function. PMID- 2581249 TI - Myasthenic serum selectively blocks acetylcholine receptors with long channel open times at developing rat endplates. AB - We have examined the physiological effects of antibodies from a highly specific myasthenic serum on acetylcholine receptors at developing rat endplates. The antibodies reduced the amplitude of miniature endplate potentials by 60% in 3- to 6-day-old animals but had no effect after day 14. Between days 7 and 12 the antibodies had an intermediate effect. This is the same period during which acetylcholine receptors with long channel open times (slow channels) disappear and receptors with short open times (fast channels) increase in number. Therefore, we examined the effect of the antibodies at endplates with a mixture of channel types more carefully. At all times tested, both noise analysis and analysis of miniature endplate currents showed that the antibodies reduced slow channel activity selectively. Single-channel recordings indicated that acetylcholine receptors that remained active after antibody treatment had normal gating properties. Thus, the antibodies appeared to silence slow channels selectively. PMID- 2581251 TI - Dissection of Mycobacterium tuberculosis antigens using recombinant DNA. AB - A recombinant DNA strategy has been used systematically to survey the Mycobacterium tuberculosis genome for sequences that encode specific antigens detected by monoclonal antibodies. M. tuberculosis genomic DNA fragments with randomly generated endpoints were used to construct a large lambda gt11 recombinant DNA expression library. Sufficient numbers of recombinants were produced to contain inserts whose endpoints occur at nearly every base pair in the pathogen genome. Protein antigens specified by linear segments of pathogen DNA and produced by the recombinant phage of Escherichia coli were screened with monoclonal antibody probes. This approach was coupled with an improved detection method for gene isolation using antibodies to clonally isolate DNA sequences that specify polypeptide components of M. tuberculosis. The methodology described here, which is applicable to other pathogens, offers possibilities for the development of more sensitive and specific immunodiagnostic and seroepidemiological tests for tuberculosis and, ultimately, for the development of more effective vaccines. PMID- 2581250 TI - Developmental and hormonal regulation of alpha 2u-globulin gene transcription. AB - Hepatic alpha 2u-globulin protein and RNA levels are under developmental and complex multihormonal control. The present studies directly evaluate the degree to which this regulation is transcriptional. alpha 2u-Globulin transcription was determined by measuring nuclear runoff RNA in vitro, and tissue alpha 2u-globulin mRNA levels were measured by dot blot hybridization. These studies reveal that (i) in male rats the transcriptional rate of the alpha 2u-globulin genes increases during postnatal development; (ii) no alpha 2u-globulin transcription is detectable in hepatic nuclei derived from hypophysectomized rats; (iii) growth hormone and glucocorticoid are both absolutely required, and glucocorticoid can replace androgen for alpha 2u-globulin gene transcription in the livers of hypophysectomized male rats; and (iv) chronic treatment of mature male rats with estrogen results in a progressive decrease in the hepatic transcription of alpha 2u-globulin genes. In all instances changes in the transcriptional rate of alpha 2u-globulin genes paralleled the tissue level of alpha 2u-globulin RNA. Thus transcriptional control predominates in regulating hepatic alpha 2u-globulin RNA levels. PMID- 2581253 TI - The 140-kDa adenovirus DNA polymerase is recognized by antibodies to Escherichia coli-synthesized determinants predicted from an open reading frame on the adenovirus genome. AB - Sequence studies of the adenovirus 2 genome have revealed the presence of a large open reading frame (ORF) from 22.9 to 14.2 map units that is believed to encode most of the adenovirus DNA polymerase (Ad Pol). An 838-base-pair fragment (19.6 17.3 map units) containing approximately 25% of this ORF has been cloned and expressed in a beta-galactosidase-chloramphenicol acetyltransferase (lacZ-CAT) expression vector under the control of the trp-lac hybrid promoter. This recombinant vector directed the synthesis of a 58-kDa lacZ-Ad Pol-CAT fusion protein that has CAT activity. This fusion protein was easily purified by affinity chromatography in which chloramphenicol, the substrate for CAT, was covalently bound to a matrix. Antisera were prepared against the purified 58-kDa lacZ-Ad Pol-CAT fusion protein and were found to react specifically with the 140 kDa Ad Pol by ELISA and immunoblot analysis. In addition, these antisera recognized 120- and 29-kDa polypeptides in immunoblot analysis of partially purified terminal protein precursor (pTP)-Ad Pol complex. The exact nature of the 120- and 29-kDa polypeptides is not known, but they may be breakdown products of Ad Pol. Although the lacZ-Ad Pol-CAT fusion protein is not active in any of the Ad Pol enzymatic reactions, antibody against the prokaryotic fusion protein should be useful for screening bacteria harboring plasmids that have been constructed to express the entire Ad Pol ORF. PMID- 2581252 TI - gamma-Fluoromethotrexate: synthesis and biological activity of a potent inhibitor of dihydrofolate reductase with greatly diminished ability to form poly-gamma glutamates. AB - A methotrexate (MTX) analog containing fluorine at the gamma-carbon of the glutamate moiety, gamma-fluoromethotrexate (FMTX), has been synthesized and evaluated for its biochemical and pharmacological properties. FMTX inhibition of dihydrofolate reductase from several sources is nearly equivalent to that shown by MTX. Most important, FMTX is an exceedingly poor substrate for folylpoly (gamma-glutamate) synthetase, the enzyme that catalyzes the biosynthesis of the highly-retained, cytotoxic MTX polyglutamates. Uptake experiments in H35 hepatoma cells show that FMTX accumulates to approximately the same extent as MTX at steady state. The rapid efflux of both derivatives is also very similar. The major difference detected in cells between the two compounds is the meager glutamylation of FMTX, due to the electronegative properties of the fluorine adjacent to the potential amide-forming carboxyl group. Exposure of dividing cells to 50 microM MTX for 2 and 6 hr results in the formation of 55 and 130 nmol, respectively, of the polyglutamates (more than two glutamate residues)/g of cell protein. With FMTX these values were reduced by 98% and 93%, respectively. Growth inhibition studies show that MTX is only 12-fold more toxic than FMTX when the cells are exposed to each derivative continuously for 72 hr. When the exposure time is reduced, a greater disparity between the inhibitory effects is observed; with a 2-hr pulse, MTX is 2300-fold more effective than FMTX. These data correlate with the effects of pulses of FMTX and MIX on de novo thymidylate biosynthesis in intact cells. The results indicate that of the parameters examined, the vastly reduced toxicity of FMTX after its removal from the culture medium is best correlated with impaired glutamylation. The data strongly suggest that prolonged toxicity of MTX is a result of metabolic conversion to MTX polyglutamates and that these effects are far more dramatic in short-term than in long-term exposure to the antifolates. PMID- 2581254 TI - Purification of the platelet-derived growth factor receptor by using an anti phosphotyrosine antibody. AB - The platelet-derived growth factor (PDGF) receptor is a 180-kDa membrane glycoprotein. A protein of identical size, lectin affinity, and isoelectric point has been identified as a major substrate for PDGF-activated tyrosine kinase in stimulated 3T3 cells. We have purified this tyrosine-phosphorylated protein to homogeneity by using anti-phosphotyrosine immunoaffinity and lectin affinity steps. Demonstration that this purified tyrosine phosphoprotein is the PDGF receptor necessitated development of an assay capable of identifying specific 125I-labeled PDGF binding activity in soluble receptor preparations. PDGF receptor solubilized from 3T3 cell membranes with the detergent octyl beta-D glucoside was precipitated on an artificial liposome matrix after receptor aggregation with concanavalin A. Precipitated binding sites display affinity and kinetic characteristics of PDGF receptors in cells and membranes. Preparations of the 180-kDa phosphoprotein that are greater than 90% homogeneous by silver stain and by [35S]methionine protein autoradiography have specific high affinity 125I labeled PDGF binding sites (equilibrium dissociation constant, 0.1 X 10(-9) M). Binding activity enrichment in this preparation reflects an 11,000-fold purification of binding activity in intact cells. These data demonstrate that the 180-kDa substrate of the PDGF-stimulated tyrosine kinase is the PDGF receptor. Furthermore, these methods provide a means of purifying this and other tyrosine kinase substrates from growth factor-stimulated cells. PMID- 2581255 TI - Nucleotide sequence of a yeast Ty element: evidence for an unusual mechanism of gene expression. AB - We have determined the DNA sequence of the transposable element Ty912 of yeast. The 5918-base-pair element encodes two genes, tya912 and tyb912, which specify proteins similar to sequence-specific DNA-binding proteins of Escherichia coli and retroviral reverse transcriptases, respectively. The tyb912 gene is atypical of eukaryotic genes since (i) it begins 1336 nucleotides into the Ty912 mRNA (i.e., downstream of the tya912 gene) and (ii) the first in-frame AUG is 921 nucleotides into the coding frame. Protein blot analysis of Ty-lacZ fusions shows that the tyb912 gene is translated starting at the 5' end of the tya912 gene and that the primary translational product is a tya912::tyb912 fusion protein. We have shown that synthesis of this fusion protein probably does not occur by RNA splicing. The data are consistent with a mechanism of translational frameshifting occurring within the region of overlap between the 3' end of tya912 and the 5' end of tyb912. PMID- 2581256 TI - Evidence that polymorphism in the murine major histocompatibility complex may be generated by the assortment of subgene sequences. AB - The high degree of polymorphism found among the class I genes of the murine major histocompatibility complex (H-2) has led to the postulation that specific genetic mechanisms are responsible for their diversity. These same genetic mechanisms are probably responsible for the high spontaneous mutation frequency seen in H-2 alleles. The bml mutation of the H-2Kb gene has been shown to be 7 base pair changes over a 13 base pair region that result in three amino acid substitutions in the C1 domain of the protein product. The clustering of base-pair changes has suggested that the bm1 mutation resulted from a recombinational event analogous to gene conversion between the H-2Kb gene and a "donor" gene sequence. A 23-base oligonucleotide complementary to the bm1 mutant sequences was synthesized and used to probe genomic DNA restriction digests of the parental H-2b haplotype as well as other H-2 haplotypes. Our results indicate that a potential donor gene sequence is present in the genomes of all of the five mouse strains studied. Of eight tissues that were tested by blot-hybridization analysis, the potential donor gene sequences are transcribed only in the liver. Models for the generation of polymorphism among the H-2 class I genes via subgene rearrangements are proposed. PMID- 2581257 TI - Involvement of I-J epitopes in the self- and allo-recognition sites of T cells: blocking of syngeneic and allogeneic mixed lymphocyte reaction-responder cells by monoclonal anti-I-J antibodies. AB - Monoclonal anti-I-Jk antibodies (mAbs) were found to inhibit syngeneic and allogeneic mixed lymphocyte reactions by blocking the responder T cells but not the stimulator cells. Only the responses of H-2k and H-2a strains were inhibited. Three different anti-I-Jk mAbs (1G8, 4B11, and KN34) showed different inhibitory patterns in allogeneic mixed lymphocyte reactions of individual H-2k strains, depending on the H-2 and immunoglobulin heavy chain variable region (IgVH) genes possessed by the stimulator strains. The results indicated that I-J epitopes are involved in the self- and allo-recognition sites of T cells, which are clonally distributed and used to recognize Ia plus IgVH-linked products. PMID- 2581259 TI - Amelioration of lytic abnormalities of paroxysmal nocturnal hemoglobinuria with decay-accelerating factor. AB - Purified decay-accelerating factor (DAF), from the stroma of normal human erythrocytes, was incorporated into the membranes of erythrocytes of patients with paroxysmal nocturnal hemoglobinuria (PNH), and its effect on the complement sensitivity of the cells was investigated. Reconstitution with exogenous DAF restored the ability of the affected PNH cells to resist assembly of the homologous C3 convertase, C4b2a, on their surfaces, and decreased the susceptibility of the cells to lysis in acidified serum. Conversely, treatment of normal erythrocytes with monoclonal or polyclonal anti-DAF antibodies abrogated the capacity of the normal cells to circumvent C4b2a assembly and rendered the cells sensitive to acid lysis. These findings show that the previously reported association of DAF deficiency with PNH is causally related to the lytic abnormalities of the cells and clarify the molecular basis for restriction of autologous convertase formation on normal human erythrocytes. PMID- 2581258 TI - A molecular basis for the Ia.2 and Ia.19 antigenic determinants. AB - The murine Ia antigens, heterodimeric glycoproteins on the surface of immunocompetent cells, restrict immune recognition by their influence on cell cell interactions. Many serological specificities have been mapped to these molecules, and monoclonal antibodies directed against some of these determinants block antigen presentation to T lymphocytes. As a step toward a better understanding of Ia function, we sought to define the molecular basis of Ia.2 and Ia.19, specificities found on the A alpha chain of only the k or of both k and r haplotypes, respectively. We report nucleotide sequences for the A alpha chain cDNAs of the k, r, and s haplotypes, which, when compared to previously published A alpha sequences, demonstrate the existence of one k-specific amino acid residue and of another present only in the k and r haplotypes. These residues must thus play an important role in the generation of Ia.2 and Ia.19 specificities. PMID- 2581260 TI - 5-Azacytidine and sodium butyrate induce expression of aromatase in fibroblasts from chickens carrying the henny feathering trait but not from wild-type chickens. AB - Male chickens with the henny feathering trait have a female feathering pattern. In two henny-feathered breeds, the Sebright bantam and the Golden Campine, the synthesis of estrogen is increased as a consequence of increased activity of aromatase, a cytochrome P-450 enzyme that converts androgen to estrogen. The activity of the enzyme is elevated in tissue slices and in cultured fibroblasts from heterozygous and homozygous birds of both breeds. In contrast, aromatase activity is very low in extraglandular tissues from control chickens and is undetectable in fibroblasts cultured from these tissues. The current studies show that two agents known to alter gene expression--5-azacytidine and sodium butyrate -markedly induce expression of aromatase activity in Sebright and Campine fibroblasts but have no effect on aromatase activity in fibroblasts from wild type chickens. Induction of aromatase is specific since two other microsomal enzymes in chicken fibroblasts--one, a component of the aromatase enzyme complex and the other a cytochrome P-450 oxidase distinct from the aromatase--are not significantly affected by these agents. Further study of this unique mutation should provide insight into the mechanisms by which genes are switched to an uninducible state during differentiation. PMID- 2581261 TI - Hybrid molecules containing the B-domain of insulin-like growth factor I are recognized by carrier proteins of the growth factor. AB - The insulin-like growth factors (IGFs) are polypeptides in plasma that are chemically related to insulin and have mitogenic and insulin-like activity. Unlike insulin, the IGFs circulate in plasma bound to specific high molecular weight carrier proteins that regulate their delivery to target tissues. To define the sites on the IGFs that allow them to be recognized by carrier proteins, we constructed hybrid molecules containing different portions of the insulin, IGF-I, and IGF-II molecules. The presence of the B domain of IGF-I, but not the D domain of IGF-II, enables these insulin-IGF hybrid molecules to be recognized by acid stripped IGF carrier proteins from rat serum and other sources. By contrast, neither the BIGF-I nor DIGF-II domain is sufficient to enable binding to type II IGF receptors, despite the fact that type II receptors, like the carrier protein, specifically bind IGF-I and IGF-II but do not interact with insulin. By differentiating those sites on the IGF molecule required for binding to IGF carrier protein and receptors, the insulin-IGF hybrid molecules should help delineate the role of the carrier protein in presenting biologically active IGF to target tissues. PMID- 2581263 TI - Birth dates of retinal ganglion cells giving rise to the crossed and uncrossed optic projections in the mouse. AB - In the mouse, as in most mammals, the crossed optic projections originate from the entire extent of the retina, whereas ganglion cells giving rise to the uncrossed (ipsilateral) projection are restricted to the temporal and ventral retina. The nasal border of this bilaterally projecting region in the retina corresponds to the midline of the visual field. Here the birth dates of ipsilaterally and contralaterally projecting ganglion cells were determined by combining tritiated thymidine labelling in the embryo with horseradish peroxidase tracings from the optic tract in the adult. Contralaterally projecting ganglion cells were found to be generated from embryonic day E11 to about E19 in a crude concentric fashion with the oldest cells in central and youngest ones in peripheral retina. Ipsilaterally projecting cells were born from E11 to E16, that is, during the earlier part of the period in which the contralateral projection was born. At the earliest time of ganglion cell generation (E11-12) ipsi- and contralaterally projecting cells were born within separate retinal regions, with the future midline representation forming the border between the two zones. This distinction became lost after E13, when both ipsi- and contralaterally projecting cells were born in the bilaterally projecting region. Hence at E11-12 the retina was found to have a bipartite organization that may allow the specification of the two maps of opposite topographical polarity in which the crossed and uncrossed projections are organized. Since in the adult retina this bipartite organization is preserved only in the large ganglion cells that project to the lateral geniculate nucleus, and since large ganglion cells are known to be the earliest ones formed in the mouse, these cells may be the ones that establish the early and bilateral projections of the retina. The conclusion that the bilateral projection system in the retina reflects an early developmental programme, and not the result of competition between the two eyes at later stages, was reinforced by observing a practically normal retinal origin of ipsilateral projections in mice which had only one normal eye from the earliest stages of eye development. PMID- 2581262 TI - Two distinct Ca-dependent K currents in bullfrog sympathetic ganglion cells. AB - Healthy bullfrog sympathetic ganglion cells often show a two-component afterhyperpolarization (AHP). Both components can be reduced or abolished by adding Ca-channel blockers or by removing external Ca. Application of a single electrode "hybrid clamp"--i.e., switching from current- to voltage-clamp at the peak of the AHP, reveals that the slow AHP component is generated by a small, slow, monotonically decaying outward current, which we call IAHP. IAHP is blocked by Ca-removal or by apamin and is a pure K current. It is slightly sensitive to muscarine and to tetraethylammonium ion but is much less so than muscarine sensitive (IM) and fast Ca-dependent (IC) K currents. It also can be recorded in dual-electrode voltage-clamp experiments, where it is seen as a slow, small component of the outward tail current that follows brief depolarizations to 0 mV or beyond. IC is seen as an early, fast, large component of the same tail current. Both components are blocked by Ca removal, but only the IC component is blocked by low doses of tetraethylammonium ion. Thus, bullfrog ganglion cells exhibit two quite distinct Ca-dependent K currents, which differ in size, voltage sensitivity, kinetics, and pharmacology. These two currents also play quite separate roles in shaping the action potential. PMID- 2581264 TI - Polyadenylic.polyuridylic acid in the cotreatment of cancer. AB - The biological properties of polyadenylic . polyuridylic acid (Poly(A) . Poly(U] are discussed and the application to the treatment of cancer in various animal models is described. Pharmacokinetic properties are presented and the results of clinical application to humans with specific reference to adjuvant treatment of breast cancer are examined in some detail. Given these results and the total lack of toxicity or of secondary effects of Poly(A) . Poly(U) it appears that further development and application of this polynucleotide complex are certainly justified in terms of clinical use in cancer and perhaps in viral pathologies. PMID- 2581265 TI - Developmental status of sympathetic innervation in relation to calcium accumulation by submandibular gland following reserpine, surgical sympathectomy or cyclocytidine. AB - Sympathectomy (Sx) of the submandibular gland was induced at various postnatal ages by ip administration of a single dose of reserpine or by unilateral excision of a superior cervical ganglion. If animals were 12 days old or less at the time of drug administration, [Ca] of the submandibular gland was not measurably increased 24 hr later; if rats were 14 days of age or older, [Ca] of the gland 24 hr after reserpine injection was nearly double that of untreated controls. Two days after surgical Sx, [Ca] of the denervated submandibular gland was unchanged from that of the innervated member of a pair if animals were less than 14 days of age at the time of denervation; [Ca] was twice that of glands of control rats if animals were older than 14 days of age when the denervation was performed. The anti-tumor agent, cyclocytidine (CC), given daily for 3 days in an ip dose of 500 mg/kg, also caused a two- to threefold increase in [Ca] of the submandibular gland when rats were more than 12 days of age at the time of the initial injection of the drug, but in rats younger than this age, CC caused no change in the [Ca] of the submandibular gland. Present data show that there are age-related differences in the ability of the submandibular gland to accumulate calcium following sympathetic denervation or treatment with a norepinephrine-releasing drug. These differences may be attributed either to incomplete development of calcium transport mechanisms, or incomplete development of the sympathetic innervation before 14 days of age. PMID- 2581267 TI - Neurotropic drugs and brain development: effects on cell replication in vivo and in vitro. PMID- 2581266 TI - Substrate and regulatory functions of eicosapentaenoic and docosahexaenoic acids for the 5-lipoxygenase pathway. Implications for pulmonary responses. PMID- 2581268 TI - Cytotoxic base propenals and the action of bleomycin. PMID- 2581269 TI - Interferon induction in vitro by polyribonucleotides and intercalating drugs. PMID- 2581270 TI - The interaction of antigen and the histocompatibility molecule during T cell activation. PMID- 2581271 TI - Computer prediction of protein surface features and antigenic determinants. PMID- 2581272 TI - Theoretical prediction of the determinants of transplantation antigens. PMID- 2581273 TI - Sensitive detection of neuroblastoma cells in bone marrow for monitoring the efficacy of marrow purging procedures. PMID- 2581274 TI - Impact of alpha fetoprotein in differentiation of human neuroblastoma cells. PMID- 2581275 TI - The effects produced by prostaglandin D2 on serotonin turnover and release and tryptophan uptake. AB - In earlier studies, it was proposed that there was a serotonergic involvement in the ability of prostaglandin D2 (PGD2) to potentiate pentobarbital sleeping time. The actions of PGD2 on neuronal turnover and release of serotonin and uptake of tryptophan were examined in mice. The effect of PGD2 administration on serum tryptophan levels was also investigated. PGD2 (1 and 4 mg/kg) increased the concentrations in whole brain of endogenous tryptophan (TRYP) and of 3H tryptophan (3H-TRYP) following an intravenous (IV) injection of 3H-tryptophan. Formation of 3H-5-hydroxyindoleacetic acid (3H-5HIAA) was doubled after PGD2 administration (1 and 4 mg/kg). Whole brain concentrations of endogenous serotonin (5HT) and 3H-serotonin (3H-5HT) were unchanged after the administration of the prostaglandin. PGD2 (10(-4) to 10(-10)M) in vitro had no effect on spontaneous or K+-evoked release of 3H-5HT from whole brain synaptosomes. Uptake of 3H-tryptophan in synaptosomes was neither stimulated nor depressed by (10(-4) to 10(-12)M) PGD2. There was also no change in serum tryptophan levels after administration of this prostaglandin. Thus, PGD2 administration does affect the serotonergic system but no direct neurochemical correlate of sedation can be shown. PMID- 2581276 TI - Ethanol-induced inhibition of the drinking response to hypertonic saline in the rat. AB - The effects of ethanol, in doses of 0.05, 0.1 and 0.2 ml/100 g, on the drinking responses of rats to subcutaneous injection of hypertonic saline (1 mEq/100 g) were examined. Rats were also studied for the effects of ethanol (0.1 ml/100 g) on drinking responses to intraperitoneal injection of dextran (20% w/v, 1.5 ml/100 g). After injection of hypertonic saline, rats given ethanol drank less than those administered water or isocalorific glucose. Ethanol inhibited the drinking responses to hypertonic saline dose-dependently with higher doses having a greater inhibitory effect. Ethanol administration had no effect on water consumption stimulated by intraperitoneal injection of dextran. It is concluded that administration of ethanol to rats has a dose-dependent inhibitory effect on thirst and fluid consumption stimulated by injection of hypertonic saline but is without effect on thirst and drinking stimulated by intraperitoneal injection of dextran. PMID- 2581277 TI - Prevention of strychnine-induced seizures and death by the N-methylated glycine derivatives betaine, dimethylglycine and sarcosine. AB - Betaine (N,N,N-trimethylglycine) and N,N-dimethylglycine have been reported to have anticonvulsant properties in animals. The purpose of the present study was to determine whether these compounds can antagonize strychnine-induced seizures when administered intraperitoneally and to compare their effects with those of sarcosine (N-methylglycine) and glycine. Betaine, N,N-dimethylglycine and sarcosine were equipotent in decreasing the incidence of seizures and death, causing a 38 to 72 percent decrease in the incidence of seizures and death at a dosage of 5 mmole/kg. Glycine had no effect. Thus anticonvulsant activity is conferred to glycine by a single N-methylation. PMID- 2581278 TI - Impact of recombinant DNA technology in pharmacology. PMID- 2581279 TI - The effect of substance P on the mechanical and electrical responses of frog, chick and rat skeletal muscle. AB - The effect of substance P (SP) on the electrical and contractile responses of skeletal muscles of frog, chick and rat were studied using electrophysiological techniques. In low concentrations, SP increased the amplitude of twitch and tetanic contractions in response to motor nerve stimulation of frog, chick and rat preparations, increased the amplitude and duration of frog sciatic nerve compound action potential and reduced the contracture responses produced by acetylcholine (ACh) or tetraethylammonium (TEA) in the chick skeletal muscle. In all these actions, the effect of SP was calcium-dependent. The results provide evidence that SP had a dual action; a prejunctional facilitatory effect by causing a further release of ACh and/or Ca2+ entry or release, and postjunctional effect by reducing the sensitivity of the postjunctional membrane to depolarizing drugs. PMID- 2581280 TI - [Treatment of malignant neoplasms. 2]. PMID- 2581281 TI - Clinical correlates of septum pellucidum cavities: an unusual association with psychosis. AB - Cavities in the septum pellucidum are widely regarded as incidental findings of little clinical importance. The prevalence of such cava on computerized tomography in a mixed sample of 22000 neurological and psychiatric patients is found to be 0.15%. A statistical association between this anomaly and a referral diagnosis of functional psychosis is reported, and 6 cases are described. These cases were male and characterized by an early history of developmental delay, with lifelong disturbances of emotion and behaviour prior to the onset in early adulthood of an atypical schizophrenia-like psychosis with disorders of speech and movement. It is suggested that septal cavities may signal an underlying abnormality of function relevant to the pathogenesis of these illnesses. PMID- 2581282 TI - Conversion disorders: an overview. PMID- 2581283 TI - Organic manic disorders. PMID- 2581284 TI - Neuropeptides in human brain--postmortem studies. AB - Four neuropeptides (substance P, methionine-enkephalin, neurotensin and cholecystokinin) were measured by radioimmunoassays in a number of brain regions of deceased patients with mental illnesses and controls. The most striking finding in these studies was that methionine-enkephalin concentrations in caudate nuclei of chronic paranoid schizophrenic patients were reduced relative to several control groups. Neuroleptics had no obvious effects on any of the four measured neuropeptides. These findings are not inconsistent with the hypothesis that methionine-enkephalin may be involved in some of the pathology of the schizophrenic syndrome. PMID- 2581286 TI - Regulatory peptides in the lower esophageal sphincter of man. AB - Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from achalasia or hiatus hernia with gastro-esophageal reflux. The specimens were analysed for neurohormonal peptides using immunochemistry and immunocytochemistry. Control specimens were obtained from patients subjected to esophageal resection because of esophageal cancer. The concentration of vasoactive intestinal polypeptide (VIP) was higher and the VIP nerve supply greater in patients with hiatus hernia than in control patients. The VIP nerve supply and the content of this peptide was lower in patients with achalasia than in controls. The same tendency was observed for substance P and enkephalin although the changes in their concentrations were not statistically significant. Enkephalin fibers were few, both in specimens from control patients and from patients with hiatus hernia; they could not be detected in specimens from patients with achalasia. Never fibers containing somatostatin or gastrin/cholecystokinin could not be detected in any of the groups and somatostatin and gastrin/cholecystokinin could not be measured in extracts of the lower esophageal sphincter. We propose that changes in the concentration of neuropeptides may at least contribute to manifestations of achalasia and of decreased lower esophageal sphincter pressure and gastro-esophageal reflux. PMID- 2581285 TI - Binding studies of substance P anterior pituitary binding sites: changes in substance P binding sites during the rat estrous cycle. AB - Previous studies have shown that substance P (SP), an undecapeptide widely distributed in the gastrointestinal tract and in the peripheral and central nervous system, is a putative regulatory peptide involved in the control of reproductive function. Specifically, SP inhibited, at the anterior pituitary (AP) level, the stimulatory action of a physiological concentration (10(-8) M) of Gonadotropin Releasing Hormone (GnRH) on the release of the luteinizing hormone (LH). In the present work, we have demonstrated the presence of specific SP binding sites in the AP and related changes in the number of these sites to GnRH receptor number, hypothalamic SP and GnRH content and LH secretion during the rat estrous cycle. High affinity saturable SP binding sites (Kd, 1.5 approximately equal to 10 nM) were demonstrated in AP membranes using [3H]-SP or a novel analog, [125I]-(D-Tyr0, NorLeu11)SP. The binding affinity of SP fragments decreased with progressive removal of amino acid residues from N or C termini of the molecule. Other neuropeptides had low affinity for the SP binding sites. During the rat estrous cycle, SP and GnRH binding capacity of the anterior pituitary were inversely related. At the time of the proestrous LH surge, the AP binding capacity was low for GnRH but high for SP. The highest content of SP in the hypothalamus were recorded during the afternoon of proestrus when hypothalamic GnRH levels were lowest and the preovulatory surge occurred. These studies have established the presence of high affinity specific binding sites for SP in the AP which alter during the estrous cycle in a manner appropriate for mediating the direct inhibitory effects of SP on LH release in vitro. PMID- 2581287 TI - Regional distribution and in vivo release of tachykinin-like immunoreactivities in rat brain: evidence for regional differences in relative proportions of tachykinins. AB - The regional distribution of various forms of tachykinin-like immunoreactivity (TKLI) was studied in rat brain using radioimmunoassay. TKLI was measured with two different tachykinin-antisera (K12 and E7), which react with neurokinin A (NKA) and neurokinin B (NKB) but not with substance P (SP) and with a specific SP antiserum. TKLI-K12 and TKLI-E7 were found to have similar regional distributions which were, however, significantly different from that of the substance P-like immunoreactivity (SPLI). Thus, the ratio of the tissue concentrations of TKLI-K12 or TKLI-E7 to that of SPLI was higher in frontal cortex and hippocampus and lower in pons/medulla oblongata than in the other regions studied. Cation-exchange chromatography of neutral water extracts of brain tissue revealed two major immunoreactive components of TKLI-K12 and TKLI-E7, one of which co-eluted with synthetic NKB while the other appeared in the same region as synthetic NKA. The relative quantities of these components varied depending on the brain region studied. No TKLI-K12 or TKLI-E7 co-eluted with synthetic SP. Almost all of the SPLI in acetic acid or water extracts of brain tissue eluted as a single chromatographic component in the same position as synthetic SP. Potassium stimulated in vivo release of TKLI-K12, TKLI-E7 and SPLI in striatum of rat brain could be demonstrated using intracerebral dialysis. The present results imply that tachykinins, which may serve as neurotransmitters or neuromodulators, are present in different proportions in different regions of rat brain. PMID- 2581288 TI - [Pharmacologic hypoprothrombinemia. A rare cause of upper digestive hemorrhage]. PMID- 2581289 TI - [Adenosine as endogenous calcium-antagonist: in vitro study on polymorphonuclear leukocytes]. PMID- 2581290 TI - The role of radiotherapy in the management of small cell bronchogenic carcinoma. PMID- 2581291 TI - Possibilities and limitations of cytological diagnoses of small cell bronchogenic carcinoma. AB - We investigate the possibilities and limitations of cytological examinations of small cell bronchogenic carcinoma by considering the results of cytodiagnoses of malignancy and histogenesis from both exfoliative and biopsy material. When a diagnosis is made from biopsy material the accuracy rate is found to be 99% for cytology, indicating that the rate for histology could be improved by as much as 20%. In peripheral small cell bronchogenic carcinoma, examination of catheter biopsies was seen to be superior to that of sputum or aspirates. When exfoliative material was used, however, only about half the cases admitted of diagnosis. Determination of histogenesis appears to depend largely on the type of material examined, and the accuracy rates vary between 70% and 95%. It is clear that the results obtained with cytological methods are considerably better than those obtained with preoperative and intraoperative histological methods. PMID- 2581292 TI - Transmembrane Na/K exchanges under electromagnetic fields. Preliminary study on human erythrocytes. PMID- 2581293 TI - Biogenic amine alterations in limbic brain regions of muricidal rats. AB - Endogenous levels of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), dopamine, 3 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured in eight brain regions of muricidal (mouse killing) and non-muricidal rats. The regions studied were: the frontal cortex, caudate nucleus, septal area, hypothalamus, thalamus, amygdalae with pyriform cortex, anterior hippocampal formation, and brain stem. Serotonergic systems showed significant differences in discrete brain regions of muricidal rats as compared to those of non-muricidal rats. The differences were: significantly higher serotonin levels in the amygdalae and significantly higher 5-HIAA levels in the hippocampus of the muricidal rats. Serotonin levels were also higher in the hypothalamus of the muricidal rats, but the difference reached only borderline significance. Dopaminergic systems also showed significant differences in the septum of muricidal rats, where DOPAC levels were significantly lower than those of non muricidal rats. The hippocampus of muricidal rats showed significantly higher dopamine levels. HVA levels in the hippocampus of muricidal rats were also higher but reached only borderline significance. These data suggest both central serotonergic and central dopaminergic involvements in rat muricidal behavior. The discrete brain regions which showed differences further suggest a limbic involvement. PMID- 2581295 TI - Modification of the function of cardiac subcellular organelles by insulin. AB - Although insulin is known to elicit a positive inotropic effect in cardiac-muscle preparations, little is known concerning the mechanism responsible for this action. Because various subcellular organelles such as mitochondria, sarcoplasmic reticulum (SR), sarcolemma, and myofibrils are intimately involved in determining the cardiac contractile function, the effects of insulin (0.1-1000 mU/ml) on some selected enzymatic activities associated with these organelles were investigated. Insulin significantly enhanced Ca2+ uptake and Ca2+-stimulated ATPase activities of SR preparations obtained by two different methods. Insulin had no effect on mitochondrial Ca2+ uptake and ATPase activities or myofibrillar ATPase activities. Sarcolemmal Na+, K+-ATPase activity was stimulated only in the presence of 1 U/ml insulin, whereas sarcolemmal Ca2+ pump activity was increased by all insulin concentrations employed. Sarcolemmal Ca2+-ATPase activity and ATP independent Ca2+ binding were augmented in the presence of 1 U/ml insulin only. These subcellular effects of insulin, either alone or in concert, may partially explain the positive inotropic action of insulin. PMID- 2581294 TI - Insulin action on cardiac glucose transport. Studies on the role of the sodium pump. AB - Isolated muscle cells from adult rat heart have been used to study the relationship between myocardial glucose transport and the activity of the Na+, K+ pump. 86Rb+ uptake by cardiac cells was found to be linear up to 2 min, with a steady state reached by 40-60 min, and was used to monitor the activity of the sodium pump. Both the ouabain-sensitive and ouabain-insensitive 86Rb+ uptake by cardiac cells were found to be unaffected by insulin treatment under conditions in which a significant stimulation of 3-O-methylglucose transport occurred. 86Rb+ uptake was markedly reduced by the presence of calcium or magnesium or both, but remained unresponsive toward insulin treatment. Inhibition of the sodium-pump activity by ouabain and a concomitant shift in the intracellular Na+/K+ ratio did not affect basal or insulin-stimulated rates of 3-O-methylglucose transport in cardiac myocytes. The data argue against a functional relationship between the myocardial Na+, K+ pump and the glucose-transport system. PMID- 2581297 TI - The antigenic characteristics and the significance of the adenine nucleotide translocator as a major autoantigen to antimitochondrial antibodies in dilated cardiomyopathy. AB - To obtain further knowledge of the antigen-antibody system, immunochemical characterization of the adenine nucleotide translocator was achieved by crossed immunoelectrophoresis, immunoreplica technique, radioimmunoassay, immunoabsorption studies, and nucleotide-transport measurements. Sera of 18 patients with proven congestive cardiomyopathy (CCM) were tested. On the adenine nucleotide translocator (ANT) from heart, kidney, and liver, organ-specific antigenic determinants were demonstrable, although a partial cross-reactivity existed. Conformation specificity was also confirmed by experimental studies. Of the patients studied, 17 of 18 with CCM showed a significant binding to the heart ANT, while no or a lower binding was seen on the kidney/liver ANT. In CCM, a correlation exists between the ejection fraction and the anti-ANT titer. These results give new evidence for autoimmunological events in MC and CCM and indicate a possible causal relationship between these two diseases. PMID- 2581296 TI - Regulation of rates of lipolysis in isolated myocardial cells from rat heart. AB - Rates of lipolysis in isolated myocardial cells (myocytes) from rat heart, as measured by the release of glycerol and a reduction in endogenous triacylglycerols, can be stimulated by isoproterenol. Myocyte preparations were calcium-tolerant and were quiescent, even in the presence of isoproterenol, so the stimulation of lipolysis by isoproterenol cannot be secondary to a physiological (inotropic) response. N6-Phenylisopropyladenosine did not reduce isoproterenol-stimulated rates of lipolysis. Increasing the calcium concentration in the incubation medium from 0.75 to 3 mM did not increase the basal output of glycerol. Furthermore, incubation of calcium-tolerant myocytes in the absence of calcium had no effect on either basal or isoproterenol-stimulated rates of lipolysis. Therefore, calcium ions must not influence the lipolytic process directly, and so the calcium dependency for lipolysis observed with perfused heart preparations must reflect the effect of calcium on the contractile performance of the heart, which only secondarily produced a change in rates of lipolysis. PMID- 2581298 TI - Role of the cholinergic system in the modulation of ventricular arrhythmias induced by subepicardial epinephrine in the dog. AB - The modulating role of the cholinergic system in epinephrine (EP)-induced ventricular arrhythmias (VAs) was studied in anesthetized (alpha-chloralose and pentobarbitone sodium) dogs. Unifocal VAs were produced by subepicardial infusion of EP (4 X 10(-3)M) in 2.5 X 10(-3) M CaCl2-0.9% NaCl at a rate of 10 microliter/min for a maximum period of 10 min at a time. One of the interacting drugs acetylcholine Cl (ACh), carbachol Cl (CCh), physostigmine salicylate (PHY), DL-propranolol HC1 (PROP), quindine HC1 (QD), lidocaine HC1 (LD), and atropine sulfate (AT) was given in an equimolar concentration (4 X 10(-3)M) along with EP. The effects of bilateral vagotomy (VT) were also studied. The time of onset, frequency, and duration of VAs were recorded. Reproducible cognizable VAs (less than 10%) were produced by EP in 38 of 43 experimental dogs. Focal infusion of the cholinomimetic agent ACh or CCh marketedly inhibited the arrhythmogenic activity of EP at the focal site. The effect of the anticholinesterase agent PHY was similar. These experiments showed that exogenous administration of a cholinomimetic agent or focal facilitation of endogenous cholinergic influence had an antiarrhythmic activity against EP. On the other hand, bilateral VT or focal infusion of AT markedly potentiated the arrhythmogenic potentiality of EP. Thus, it appeared that removal of endogenous influence facilitated EP-induced arrhythmias. The antiarrhythmic activities of the beta-adrenoceptor-blocking agent PROP and the membrane-stabilizing agents LD and QD against EP were confirmed using the subepicardial infusion technique. These studies show that the presence of cardiovagal tone or its facilitation inhibits, and its blockade increases, the propensity to VAs in situations in which the adrenergic system may be involved primarily or otherwise. The receptors involved appear to be muscarinic in nature. PMID- 2581299 TI - The role of Ca influx in cardiac muscle excitation-contraction coupling. Assessment by extracellular Ca microelectrodes. AB - Tension, dT/dt, and extracellular free [Ca] [( Ca]0) were continuously measured in isolated rabbit right papillary muscles at 28 degrees C. Double-barreled Ca selective microelectrodes incorporating Simon's neutral Ca exchange resin (ETH 1001) were used to monitor [Ca]0. Decreases of [Ca]0 were seen during the course of single twitches, before the development of significant tension. This depletion of Ca0 probably represents Ca influx into the cells from the extracellular space. The magnitude of this Ca0 depletion is decreased by Co, verapamil, long rest intervals, and reduction of [Ca]0. The magnitude is increased by catecholamines, reduction of [Na]0, caffeine, continued pacing, and elevation of [Ca]0. After 3 min rest, stimulation (0.5-1 Hz) produces a biphasic tension response (larger first beat, small second beat, and monotonic rise to control). Caffeine (5 mM) changes the pattern after rest to a monotonic increase. Ca influx increases monotonically in both cases. Addition of 20 mM Co during the rest reduces tension of all beats by similar amounts in the presence of caffeine. In the absence of caffeine, Co has a much weaker effect on the first beat than on subsequent beats. The results suggest that caffeine inhibits an intracellular component of activator Ca that is more important after a rest interval, but that Ca influx becomes increasingly more important during continued pacing under the conditions used here. PMID- 2581300 TI - Reperfusion-induced ventricular fibrillation. Modification by pharmacological agents. AB - We have assessed the ability of several of the main groups of antiarrhythmic agents to modify the incidence of reperfusion-induced ventricular fibrillation in the isolated working rat heart preparation with transient coronary artery occlusion. Hearts were perfused with Krebs-Henseleit medium containing 5 microM epinephrine to provide some level of exogenous catecholamine support. Compounds selected were: the fast sodium channel inhibitors lignocaine (1 and 10 microM) and prenylamine (4 microM) (the latter also possessing slow calcium channel antagonistic actions); the beta-adrenergic blocking agents oxprenolol (1.2 microM), timolol (0.13 microM), metoprolol (1.0 microM), and acebutolol (5.6 microM); and the slow calcium channel antagonist nifedipine (0.05 and 0.5 microM). After 15 min of coronary artery occlusion, over 90% of control hearts fibrillated 30-60 sec after the onset of reperfusion. Drugs reduced this to the following: prenylamine, 0% (p less than 0.001); 1 microM lignocaine, 83%; 10 microM lignocaine, 33% (p less than 0.01); oxprenolol, 92% (NS); timolol, 92% (NS); metoprolol, 42% (p less than 0.01); acebutolol, 67% (p less than 0.05); 0.05 microM nifedipine, 83% (NS); and 0.5 microM nifedipine, 67% (NS). Thus, inhibition of the fast inward sodium channel with agents such as prenylamine and lignocaine, (when begun before coronary-artery occlusion) offers maximal protection against reperfusion-induced ventricular fibrillation, while beta blockade with timolol and oxprenolol and slow calcium channel inhibition with nifedipine do not offer any significant protection. The beta-blocking agents metoprolol and acebutolol produce a partial reduction that may be due to a membrane-stabilizing action, rather than to beta-blockade. PMID- 2581301 TI - Calcium agonism, a new mechanism for positive inotropy. Hemodynamic effects and mode of action of BAY K 8644. AB - BAY K 8644 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethyl -phenyl) pyridine-5-carboxylate] is a nifedipine-like 1,4-dihydropyridine (DHP). In contrast to the well-known calcium antagonistic DHPs, it has vasoconstricting and positive inotropic properties. In the pentobarbital-anesthetized dog, it increases blood pressure, peripheral resistance, and left ventricular (dP/dt)max dose-dependently from 3 to 100 micrograms/kg i.v. If the vagus is blocked, heart rate is unchanged. In the isolated isovolumic perfused guinea pig heart, BAY K 8644 has positive inotropic and coronary constricting actions from 10(-9) mole/liter. At 10 times higher concentrations, this compound also increases the heart rate up to 20%. BAY K 8644 has no effect on rabbit aortic strip at physiological K+ concentrations, but potentiates the K+ -induced contraction of the strip. In the partially depolarized aortic strip (18 mM K+), BAY K 8644 induces concentration-dependent contractions, which are competitively inhibited by the calcium-antagonistic DHP nifedipine. Chemically different calcium antagonists such as verapamil or diltiazem inhibit the BAY-K-8644-induced contractions noncompetitively. These results indicate that a specific DHP receptor exists, which binds nifedipine and BAY K 8644. In contrast to the calcium-antagonistic DHPs like nifedipine, BAY K 8644 increases the calcium influx into the cell. PMID- 2581302 TI - Differing potencies and dose-response characteristics in the ability of slow calcium-channel blockers to reduce enzyme leakage in the calcium paradox. AB - In studies of the calcium paradox, we have used an isolated rat heart preparation to investigate the relationship between myocardial creatine kinase leakage and the concentration of slow-calcium-channel blockers (nifedipine or verapamil) in the perfusion fluid during a cycle of calcium reduction and repletion. The results indicated that enzyme leakage could be further reduced to a degree greater than that seen under conditions of a full calcium paradox (complete calcium depletion). Detailed dose-response studies with verapamil and nifedipine at a calcium concentration of 1.0 mM during a 20-min period of calcium repletion following a 10-min period of calcium reduction (12 microM calcium) revealed complex dose-response characteristics for each drug. In the dose range studied (0 20 microM), nifedipine was able to reduce enzyme leakage maximally by 57 +/- 8% and verapamil by 37 +/- 4%. Optimal concentrations for verapamil and nifedipine were 4.0 and 2.0 microM, respectively. Both drugs exhibited bell-shaped dose response curves without a loss of efficacy at higher concentrations. There was no resumption in contractile activity in the drug-treated groups. Simultaneous use of verapamil and nifedipine at their optimal concentrations failed to improve the reduction in enzyme leakage to a reduction greater than that observed with one drug alone. PMID- 2581304 TI - Recapillarization of tenotomized skeletal muscles after delayed tendon suture. I. Experimental study. AB - The investigation was under taken to study the long-term effect of tendon suturing on the capillarization of guinea-pig crural muscle after Achilles tenotomy. The results indicate that the capillary density has been greatly decreased by the tenotomy. The recapillarization and the time of restitution of the crural muscle are influenced by the interval between tenotomy and tendon suture. PMID- 2581303 TI - Effects of noradrenaline on the sodium pump of guinea pig ventricle. AB - The effect of noradrenaline on myocardial sodium-pump activity has been studied, using a direct measure of active ion transport via the pump; namely, the ouabain sensitive uptake of the radioisotope and potassium analogue rubidium-86 into guinea pig ventricular tissue slices. Physiological concentrations of noradrenaline caused a dose-dependent stimulation of rubidium uptake (peak response at 2 X 10(-7) M). With higher concentrations, the uptake fell progressively. At 6 X 10(-5) M, noradrenaline uptake was lower than control. The stimulatory action is not mediated by classic adrenergic mechanisms. It was not blocked by either alpha- or beta-blockade. Indirect actions via changes in membrane permeability to sodium and potassium ions are also considered. The inhibitory effect of high concentrations of noradrenaline, however, was mediated by alpha-receptors. Stimulation of the pump by noradrenaline could stabilize cellular ion concentrations and resting membrane potential. Since the pump is electrogenic, this is one mechanism by which noradrenaline will cause shortening of action potential. This may provide an explanation for the greater Q-T shortening during exercised-induced tachycardia, compared with atrial pacing. At high concentrations, attained locally during maximal sympathetic stimulation, these advantageous effects may be lost. PMID- 2581305 TI - Cholinesterase evaluation in the prenatal diagnosis of open neural tube defects. AB - Alpha-fetoprotein (AFP) and cholinesterase levels in amniotic fluid were determined and the efficiency of these laboratory tests in the prenatal diagnosis of neural tube defects was examined. Using the AFP test with cut-off levels correlated to gestational age, we have detected 8 cases of neural tube defects and one case of abdominal wall defect in about 1,200 pregnancies; false-negative values were absent. Acetylcholinesterase (AChE) and butyrylcholinesterase activities were measured and the electrophoretic pattern of AChE was examined in 100 amniotic fluid samples. The diagnosis of neural tube defects was always confirmed. There were no diagnostic problems due to blood-contaminated amniotic fluid samples. The results obtained using different quantitative methods for the determination of cholinesterase activity, as well as the potential use of these tests in routine examinations, are discussed. PMID- 2581306 TI - Effect of pineal treatment on testicular biochemical parameters under basal conditions and after stimulation with HCG in the rat. AB - The effect of a melatonin-free pineal extract on sialic and ascorbic acid, nucleic acids (DNA RNA), proteins, total, free and esterified cholesterol in the rat testis under basal conditions and after stimulation with HCG was followed up. The pineal extract induced a decrease in sialic and ascorbic acid, total and esterified cholesterol, but it increased the proteins and RNA after 3 days of treatment, under basal conditions. The decrease in RNA and proteins was noticed after 30 days of treatment. Administration of HCG increased the sialic and ascorbic acids and decreased the total and esterified cholesterol, proteins and DNA without affecting RNA and free cholesterol in the testicular tissue. Concomitant administration of HCG and pineal extract showed that the pineal treatment corrected partially and sometimes completely the increasing or decreasing effect produced by HCG on the biochemical indices studied. The decrease in testicular esterified cholesterol the latter associated with androgen hormone synthesis, brings into discussion the role of the pineal gland in testicular testosteronogenesis, as the same pineal extract also caused a decrease in testosterone. The authors also discuss the regulating role of the pineal gland on some testicular biochemical indices. PMID- 2581307 TI - Influence of glucocorticoids on prenatal development of the gut and pancreas in rats. AB - The effect of chronic administration of hydrocortisone during pregnancy on growth and maturation of the foetal gut and pancreas was investigated. Groups of 10- to 11-day pregnant rats were injected with saline or hydrocortisone (50 mg/kg) once a day for 10 days. The pancreas, antrum, and small intestine of newborns (8-10 h after birth) were analysed for various determinants of growth and maturation. The small-intestinal weight and DNA, RNA, and protein were significantly higher in newborns from hydrocortisone-treated animals than those of saline-treated controls. Hydrocortisone treatment resulted in an induction of sucrase and significantly stimulated total lactase activity. After the steroid treatment during pregnancy, the weight of the pancreas and its DNA content in newborns were also significantly elevated when compared with those from saline-treated controls. However, neither pancreatic RNA nor protein content differed significantly between the groups. Antral gastrin content in newborns from hydrocortisone-treated mothers was significantly higher than that from saline treated controls. Pancreatic gastrin content in newborns was slightly but not significantly reduced after the steroid administration to mothers. It is concluded that glucocorticoids induce growth and maturation of foetal gut and pancreas. PMID- 2581308 TI - A randomized trial of iohexol versus amidotrizoate in endoscopic retrograde pancreatography. AB - To evaluate whether a low-osmolar contrast medium could decrease hyperamylasemia after endoscopic retrograde pancreatography, a prospective randomized double blind trial of 54 consecutive patients with suspected pancreatic disease referred for endoscopic retrograde pancreatography was performed. The low-osmolar contrast medium iohexol and high-osmolar amidotrizoate were used. No statistically significant differences with regard to rise in pancreatic-type amylase, pain reaction, or diagnostic information were found. No case of acute pancreatitis was observed. PMID- 2581309 TI - The effects of vagal nerve stimulation on endoluminal release of serotonin and substance P into the feline small intestine. AB - Endoluminal release of serotonin (5-HT), substance P (SP), and motilin was quantitated after thoracic vagal nerve stimulation in the cat. In duodenum and jejunum, simultaneous release of these compounds was observed. In contrast, vagal stimulation did not augment the rate of luminal secretion of either 5-HT or SP in the distal ileum. Immunohistochemical studies demonstrated 5-HT in both enterochromaffin (EC) cells and nerves throughout the small bowel. However, we were unable to visualize any SP-containing EC cells in the cat, which suggests that the source of luminal SP in this species must be intramural nerves. PMID- 2581310 TI - Adaptation of the May-Grunwald-Giemsa staining method for automated differential counting of blood leukocytes by a Hematrak analyzer. AB - The selection of exact pH (6.85/6.90) concentrations of the stains and staining times made it possible to use the May-Grunwald-Giemsa (MGG) staining method for smears studied with a Hematrak model 240 automated differential leucocyte counter. The differences between the smears stained by the method of Wright according to the recommendations of the manufacturer and the present MGG modification resulted in non-significant differences in the recognition of various types of leucocytes. The differences between the manual method and those obtained by Hematrak for the MGG-stained samples with normal total leucocyte counts were nonsignificant with all types of leucocytes except basophils, which were underestimated by the instrument. The present staining procedure was adequate in studying of neutrophilias. When samples with lymphocytosis or with immature cells were examined, too few lymphocytes and immature cells and too many monocytes were obtained by the instrument, as compared to the manual method. PMID- 2581311 TI - Expression of the platelet-common acute lymphoblastic leukaemia associated antigen on normal eosinophils. AB - A murine monoclonal antibody (TP82) raised against normal platelets was found to be reactive with eosinophils and common acute lymphoblastic leukaemia (cALL) cells, and some blast cells from patients with non-lymphoid leukaemia. The antibody showed that the platelet-cALL associated antigen (p24) is also expressed on normal eosinophils, and may prove useful for studying the function as well as the differentiation of eosinophils. PMID- 2581312 TI - Characterization of Chlamydia trachomatis serotypes by human T-lymphocyte clones. AB - T cells primed to Chlamydia trachomatis serotypes A, F, and K were cloned by limiting dilution. All T-lymphocyte clones obtained reacted only with C. trachomatis antigens. The proliferative capacity of 89 clones was studied with autologous non-T cells as antigen-presenting cells and the chlamydia serotypes A, B, D, F, K, and LGV-2 as antigens. Most of the clones reacted to several of the chlamydia strains, indicating common antigenic determinants. Other T-cell clones reacted with only a few serotypes. On the basis of the proliferation of the T cell clones to the chlamydia strains and to interleukin-2, different reactivity patterns were obtained, which possibly can be used to differentiate among the chlamydia strains. PMID- 2581313 TI - [Nonspecific granulomatous prostatitis. Histopathological study of 53 cases with a review of the literature]. AB - Over a 12-year period (1971-1983), 6868 prostatic biopsies were received and examined at the Department of Pathology, Geneva. 53 (0.77%) presented with non caseous granulomatous prostatitis. This lesion was associated with nodular prostatic hyperplasia in 38 cases (71.5%) and with prostatic carcinoma in one case (2%), and occurred alone in 14 cases (26.5%). The histogenesis, clinical aspects, management and prognosis of this condition are discussed in the light of current literature. PMID- 2581314 TI - Identification of human glucocorticoid receptor complementary DNA clones by epitope selection. AB - Steroid hormones regulate cellular differentiation and physiologic functions predominantly through gene transcription. Regulation is achieved by the interaction of specific steroid receptor proteins and target genes. Expression cloning techniques were used to select human glucocorticoid receptor complementary DNA clones in order to define the mechanism by which the receptor exerts its transcriptional control. Immobilized fusion proteins from individual clones were used to select epitope-specific antibody which was subsequently eluted and identified by binding to protein blots of cellular extracts. Three cross-hybridizing clones containing inserts expressing antigenic determinants of the human glucocorticoid receptor were isolated. PMID- 2581315 TI - Expression of the chlamydial genus-specific lipopolysaccharide epitope in Escherichia coli. AB - The obligate intracellular prokaryote Chlamydia trachomatis is the etiological agent of trachoma and is a primary causative pathogen of sexually transmitted genital tract disease; both diseases affect millions of people each year. The cloning of genes encoding the enzyme or enzymes producing the genus-specific lipopolysaccharide antigen of Chlamydia into Escherichia coli is reported here. The cloned chlamydial lipopolysaccharide antigen appears to be a hybrid lipopolysaccharide molecule composed of both Chlamydia and Escherichia coli components. The chlamydial lipopolysaccharide antigen is expressed on the surfaces of the viable Escherichia coli recombinants. These findings may have a significant impact on defining the role of this highly conserved antigen in the pathogenesis and diagnosis of chlamydial infections. PMID- 2581317 TI - Reversibility of progression of the transformed phenotype in Ad5-transformed rat embryo cells. AB - The carcinogenic process is extremely complex and is affected by diverse environmental and host factors. The mechanism for the gradual development of the transformed phenotype (a process termed "progression") was studied in type 5 adenovirus (Ad5)-transformed rat embryo cells. Progression was not correlated with major changes in the pattern of integration of viral DNA sequences. Instead, it was associated with an increased methylation of integrated viral sequences other than those corresponding to the E1 transforming genes of Ad5. A single exposure of progressed cells to the demethylating agent 5-azacytidine (Aza) resulted in a stable reversion to the unprogressed state of the original parental clone. A further selection of cells after growth in agar allowed the isolation of Aza-treated clones that had regained the progressed phenotype. These observations indicate that progression is a reversible process and suggest that progression may be associated with changes in the state of methylation of one or more specific genes. PMID- 2581316 TI - A vital stain for the Golgi apparatus. AB - The Golgi complex, a membranous organelle with important functions in membrane traffic and macromolecular synthesis, has been stained in living cells with a fluorescent sphingolipid. Cells were first incubated with liposomes containing N [7-(4-nitrobenzo-2-oxa-1,3-diazole)]-6-aminocaproyl sphingosine (C6-NBD ceramide), or with a bovine serum albumin complex of the fluorescent lipid, and then examined by fluorescence microscopy. An intensely fluorescent perinuclear structure was identified as the Golgi apparatus by its colocalization with known Golgi markers in fixed cells. C6-NBD-ceramide was used to observe the morphology of the Golgi apparatus in living cells in the presence or absence of monensin or Colcemid, and during mitosis. In all cases, C6-NBD-ceramide revealed a Golgi apparatus in the living cell that was identical to that obtained with conventional procedures that require fixation. PMID- 2581319 TI - Functional coupling of gamma-aminobutyric acid receptors to chloride channels in brain membranes. AB - gamma-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in mammalian brain, is believed to act by increasing membrane conductance of chloride ions. In this study it was found that GABA agonists increased the uptake of chloride-36 by cell-free membrane preparations from mouse brain. This influx was rapid (less than 5 seconds), and 13 micromolar GABA produced a half-maximal effect. The GABA antagonists (bicuculline and picrotoxin) blocked the effect of GABA, whereas pentobarbital enhanced the action. This may be the first demonstration of functional coupling among GABA and barbiturate receptors and chloride channels in isolated membranes. The technique should facilitate biochemical and pharmacological studies of GABA receptor-effector coupling. PMID- 2581318 TI - Induction of hepatitis B virus core gene in human cells by cytosine demethylation in the promoter. AB - A recombinant human cell line constructed by transfection of epithelial cells with a plasmid containing the hepatitis B virus core gene (HBc) was used to study the regulation of HBc gene expression. Methylation of a single Hpa II site 280 base pairs upstream from the structural gene was found to regulate the expression of the core gene. Expression increased in cells treated with 5'-azacytidine as a result of cytosine demethylation at this site, and there was a fivefold increase in the number of HBc gene transcripts in total cellular messenger RNA. The varied life cycle of hepatitis B virus in disease such as viral hepatitis and liver cancer may therefore be attributable to the site-specific regulation of the gene involved in replication of the viral DNA and to the cytophathic effects elicited by this gene in human cells. PMID- 2581320 TI - [Hydroxyethyl starch 450/0.7 in burn shock. Effect on edema formation]. PMID- 2581321 TI - Tetralogy of Fallot. PMID- 2581322 TI - Comparative study of mexiletine and quinidine in the treatment of ventricular ectopia. AB - Mexiletine is an antiarrhythmic agent, structurally similar to lidocaine, but useful orally as well as intravenously. The safety and efficacy of mexiletine was compared with quinidine in a double-blind, parallel, randomized study of patients with chronic ventricular ectopia of various causes. Mexiletine was statistically more effective (P less than .05) than quinidine, though the total number of patients studied was small. Like quinidine, side effects limited the usefulness of mexiletine in certain patients, but these side effects are quite distinct from those of quinidine and other type I antiarrhythmic drugs. Mexiletine should be a useful addition to the armamentarium of antiarrhythmic drugs when it is released for clinical use in the United States. PMID- 2581323 TI - [Pituitary hormones in prostatic adenoma]. PMID- 2581324 TI - Isoxicam and indomethacin in acute osteo-arthritis. A GP multicentre double-blind comparison. AB - A study was conducted in general practice to assess the efficacy and safety of isoxicam 200 mg once daily compared with indomethacin 25 mg 3 times a day in the treatment of acute exacerbations of osteo-arthritis. The trial was conducted as a multicentre, double-blind, randomized parallel-group study with 'dummy loading' of the medications. Thirty-one general practitioners entered 309 patients in the study. Of these, 139 patients on isoxicam and 137 on indomethacin completed the treatment. The most common sites of osteo-arthritis were the knee (100 patients) and the hip (79 patients). On examination at 7 days and 14 days there was a significant improvement in both treatment groups. After 7 days the reduction of pain and clinical symptoms of osteo-arthritis of the hip and knee was significant for both drugs at the P less than 0,001 level. There thus appeared to be no difference in clinical efficacy between the drugs. Eight patients in the isoxicam group experienced definite drug-related adverse reactions as against 19 in the indomethacin group. A total of 38 patients (18 on isoxicam and 20 on indomethacin) suffered probably drug-related effects. Isoxicam therefore appeared to be better tolerated than indomethacin. PMID- 2581326 TI - [Brushing instruction using computer charts]. PMID- 2581325 TI - Normovolaemic haemodilution using dextran 70 in thoracic surgery. AB - Normovolaemic haemodilution was undertaken in 10 patients requiring elective thoracic surgery. The resultant blood loss, cell loss, use of donor blood and acid-base changes were compared with those in 10 patients undergoing similar procedures who were anaesthetized in the standard manner. Normovolaemic haemodilution reduces the use of donor blood and provides more satisfactory acid base status than that in controls. The known antithrombotic effect of dextran 70 (Macrodex; Saphar) did not affect the crude clotting time. The technique is a feasible alternative to use of donor blood, especially when difficulties in supply exist or there is a high risk of disease transmission. PMID- 2581327 TI - Surgical management of chronic pancreatitis. AB - The management of chronic pancreatitis continues to achieve only limited success. A lack of understanding of the basic pathogenic mechanism of this disease limits our therapy to treatment of symptoms, sequelae, and complications. The diagnosis of chronic pancreatitis usually is based on a history of classic pain plus some objective findings of pancreatic disease. Imaging techniques, such as ultrasonography or CT, are helpful in defining the size of the gland and the presence of masses and collections of fluid. Endoscopic pancreatography, however, remains the most helpful tool for diagnosis. The information that it provides about the pancreatic ductal system can help in selecting a procedure that achieves the best result with the lowest morbidity and mortality. The principle to follow in the surgical management of this condition is to tailor the procedure in each patient to preoperative clinical information, information provided by pancreatography, operative findings, exocrine and endocrine status of the patient, presence or absence of drug addiction and alcoholism, and the personality of the patient as well as his or her ability to manage the possible metabolic complications of surgery. Although management of pain is the main goal, the morbidity and late mortality that can result from different procedures must be a major consideration in selecting therapy. Pancreaticojejunostomy is the procedure of choice at this time for patients with a dilated pancreatic duct sphincterotomy or sphincteroplasty for the occasional patient with proved ampullary obstruction of the pancreatic duct, and internal drainage for pseudocyst. Different degrees of pancreatic resection are indicated for patients with severe disease and small pancreatic ducts, in patients in whom decompressive operations have failed, in patients with lateralized disease to the head or tail of the gland, in some instances of pseudocyst or pancreatic fistulas, and for some patients when cancer cannot be ruled out. Attempts are being made to improve the limited results of our current therapy. Endoscopic occlusion of the pancreatic duct, pancreatic segmental autotransplantation, islet cell autoimplantation, use of the pyloric-preserving operation, and use of continuous subcutaneous insulin infusion are being tried. Further experience with these techniques is required to determine their value in the management of patients with chronic pancreatitis. PMID- 2581328 TI - Cushing's disease. A cause of delayed growth and development. AB - An adolescent male with a typical cushingoid appearance presented to his physician with failure of linear growth and sexual development. Although his neuroradiologic workup was negative, his endocrinologic assessment pointed to the pituitary gland as the diseased organ. Selective transsphenoidal adenomectomy has thus far resulted in normalization of cortisol and growth hormone levels and furthered linear and sexual growth. PMID- 2581329 TI - Evaluation of long-term consequences in behavioral and/or neural function following neonatal chlordecone exposure. AB - The effects of neonatal exposure of rats to chlordecone, during the major postnatal period of neuroendocrine differentiation were assessed after the animals matured to 90 days of age. On day 4 postpartum, pups received a s.c. injection of either DMSO vehicle or chlordecone (1 mg/pup) dissolved in DMSO. The neonatal exposure produced a significant sex-dependent alteration in adult body weight; chlordecone-exposed males were lighter than vehicle-exposed controls and chlordecone-exposed females were heavier than vehicle-exposed controls. Behavioral tests sensitive to neonatal chlordecone exposure during preweaning development--i.e., spectral analysis of movement, activity, and auditory startle responsiveness--gave no statistically significant evidence for residual effects of the early organochlorine treatment. When challenged with harmine, a known tremorogen with putative effects on olivocerebellar pathways, chlordecone-exposed males were less responsive than vehicle-exposed littermates in a spectral analysis of movement. The movement spectrum of chlordecone-exposed females was not differentially sensitive to the harmine challenge. However, subsequent evaluation of the auditory startle reflex indicated that harmine interacted with the neonatal treatment and sex of the animal; chlordecone-exposed males were less responsive and chlordecone-exposed females more responsive than same sex vehicle exposed littermates. The responsiveness to a d-amphetamine challenge, expressed as a ratio of baseline activity in a pre- and post-test design, suggested the chlordecone-exposed males gave an exaggerated response to the drug challenge. Collectively, these findings suggest that the neonatal chlordecone exposure had a significant organizational effect on the development of behavioral and/or neural function. These findings also suggest the predictive utility of early behavioral tests; that is, long-term alterations were noted in each component of the toxicological syndrome previously identified during preweaning development. PMID- 2581331 TI - Standardization of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4): a collaborative study to establish international standards for beta-TG and PF4. AB - An international collaborative study was carried out to determine the suitability of freeze-dried preparations of beta-TG and PF4 to serve as international standards, and to compare these materials with other purified preparations and with plasma samples. Although problems remain with the accurate measurement of these proteins, it has been demonstrated that common standards improve the precision of measurement by RIA and provide an essential foundation for future work into the effects of assay system differences. The World Health Organization established in 1984 the purified preparation of beta-TG (83/501) and the purified preparation of PF4 (83/505) as International Standards, with assigned potencies of 500 International Units per ampoule and 400 International Units per ampoule, respectively. PMID- 2581330 TI - Characterisation of epitopes on human tissue plasminogen activator recognised by a group of monoclonal antibodies. AB - Seven mouse monoclonal antibodies have been produced against human melanoma tissue plasminogen activator (t-PA). They were specifically bound to 125I t-PA but not 125I urokinase (u-PA) and inhibited t-PA, but not u-PA, activity in plasminogen-rich 125I fibrin wells. Three of the antibodies directly inhibited the amidolytic activity of t-PA and the two most effective also bound near the active site histidine residue as determined by competition experiments using active site blocking agents. Several antibodies interfered with the fibrin binding properties of t-PA. One antibody neither interacted with the active site nor inhibited fibrin binding but still effectively quenched t-PA activity in fibrin wells suggesting that it masks another region of the molecule necessary for effective biological activity. PMID- 2581332 TI - Effects of prostacyclin and of the stable prostacyclin analogue ZK 36374 on forearm blood flow and blood platelet behaviour in man. AB - PGI2 and ZK 36374 were each infused into volunteers and the effects on forearm blood flow and on platelet behaviour were determined. Infusions of PGI2 or ZK 36374 did not alter resting forearm blood flow but both agents reduced the extent of the vasoconstriction that occurred in response to cold. ZK 36374 appeared to be a much more potent inhibitor of platelet behaviour than PGI2 when blood was taken while the infusions were in progress, but the effects of both agents were no longer evident one hour after the infusions were terminated. There was an inverse relationship between the extent of cold-induced vasoconstriction and the concentration of sodium arachidonate that was needed to induce platelet aggregation for different individuals. Infusions of PGI2 affected both parameters equally but ZK 36374 had a greater effect on platelet behaviour than on blood flow. It is possible that very low doses of ZK 36374 would result in inhibition of platelet behaviour without producing adverse haemodynamic effects. PMID- 2581333 TI - Further antigenic determinants on HLA-A molecules. AB - Monoclonal antibodies detect a new polymorphic antigenic determinant shared by HLA-A2, 3, 28, 29, 30, 31 and w33. This was demonstrated by population and family studies, including an HLA-A,B recombinant family, and by lysostrip experiments. Competition experiments, measuring the binding of 125I labelled MoAbs to B lymphoblastoid cell lines coated with anti-HLA conventional alloantisera and MoAbs showed that this new epitope is spatially distant from other known epitopes of A3 molecules and from monomorphic and polymorphic determinants of A2 molecules detected by monoclonal antibodies. On the other hand, anti-HLA-A2 polyclonal alloantisera are able to inhibit binding. PMID- 2581334 TI - Evidence for a new HLA class II determinant present on cells from HLA-DR1 and/or DR4 individuals. AB - Evidence for a new HLA class II specificity is presented. It is recognized by LE serum, which reacts with most DR1 and/or DR4 individuals (r = 0.86). Its frequency in the French population is 0.33. Absorption-elution experiments showed that the serum reactivity was not due to a mixture of anti-DR1 and anti-DR4 antibodies, but to a single antibody population which could be absorbed on and eluted from both DR1(+) or DR4(+) cells. LE specificity seemed to be expressed on DR but not on DQ molecules since the serum reacted with and could be absorbed by DR+,DQw- cells; it did not react with a DR-,DQw+ mutant cell, but did react with the DR+,DQw+ parental cell. The relationship between LE specificity and MC1 and Te23 specificities remains to be determined. PMID- 2581335 TI - Evaluation of concentration procedures of mutagenic metabolites from urine of diesel particulate-treated rats. AB - Several concentration procedures of mutagenic metabolites contained in the urine of diesel particulate-treated rats were compared. Mutagenicity was monitored by the Salmonella/microsome assay. The procedures tested were: lyophilization; filtration on XAD-2, XAD-7 or Sephadex LH-20 matrices; ultrafiltration; and extraction with organic solvents. Urine extraction with dichloromethane (DCM) gave almost quantitative recovery of activity while leaving salts and other polar compounds in the aqueous phase, and is the method recommended. PMID- 2581336 TI - Sickle cell and thalassaemic genes in Libya. AB - An electrophoretic study of haemolysates from 1350 subjects from the indigenous population of Libya was carried out to find the incidence of abnormal haemoglobins and thalassaemia. Sickle cell disease was detected in five (0.37%), sickle cell trait in 61 (4.51%), sickle cell thalassaemia in three (0.21%), homozygous betathalassaemia in 16 (1.20%), heterozygous delta-beta thalassaemia in 25 (1.85%) and heterozygous beta-thalassaemia in 105 (7.77%). The incidence of the sickle cell gene is low, but that of the thalassaemic gene appears to be high in the Libyan population which is racially mixed, containing Arab, Mediterranean and Negroid types. PMID- 2581337 TI - Growth and antigenic variation of Trypanosoma brucei, T. rhodesiense and T. gambiense in subcutaneous millipore chambers. AB - The inability to cultivate infective bloodstream forms of the African trypanosomes in cell-free media has complicated studies of the biology of trypanosomes and the pathogenesis of trypanosomiasis. We attempted to overcome this problem by subcutaneous implantation in mice of Millipore chambers that isolate trypanosomes from cells but permit diffusion of soluble substances across their membranes. Chambers were inoculated with 5 X 10(4) to 5 X 10(5) per ml Trypanosoma brucei, T. rhodesiense or T. gambiense; the trypanosomes multiplied rapidly, persisted for as long as five weeks, and remained infective, even when the original inocula were freed of donor cells by ion-exchange. The presence of anti-trypanosomal IgG and IgM in the sera and chambers of recipient mice proved that trypanosomal and mammalian products crossed the membranes. Chamber trypanosomes also expressed two important aspects of normal in vivo biological behaviour: (i) differentiation from long slender to short stumpy bloodstream forms and (ii) antigenic variation. Death of trypanosomes was associated with the presence of IgM antibody in the chambers. This model provides a system for study of an entire population of trypanosomes in an extravascular, cell-free environment. PMID- 2581339 TI - Evidence that indomethacin inhibits lymphocyte-induced angiogenesis. PMID- 2581338 TI - Acinar structure and function in canine pancreatic autografts with duct drainage into the urinary bladder. AB - Autotransplants of pancreas in 8 dogs, with exocrine drainage into the urinary bladder, were stimulated in vivo with cholecystokinin-pancreozymin (CCK-PZ). Transplant biopsies, when compared with 6 normal pancreases, showed normal acinar structure by light and electron microscopy 13-18 months after initial surgery; 2 transplants with sutures unintentionally transecting ducts were fibrosed and had duct obstruction. After in vivo stimulation, the normal-appearing transplants produced a 7-fold increase in urinary amylase, and quantitative electron microscopy showed a 50% reduction in mature zymogen granules; there were no intracellular organelle abnormalities prior or subsequent to stimulation. Fibrosed transplants produced lesser urinary amylase both prior to and after stimulation. In vitro stimulation of grafts with normal structure increased amylase secretion from 1.5-2.1-fold. In vitro dose-response showed a maximum at 10(-9)M cholecystokinin-octopeptide (CCK-OP) in transplant and control. The in vivo stimulation is more responsive and may be useful for clinical monitoring of graft survival. In vivo stimulation occurred after induced urinary tract infection; because no pancreatitis ensued, a regimen of trophic stimulation by CCK-PZ was not contraindicated. The bladder tolerated exocrine drainage with no significant change, and bladder infection did not adversely affect the transplant. The islets appeared normal in the transplants by light and qualitative electron microscopic observation; fasting blood glucose and insulin values were normal during the 12-18-month follow-up. Bladder drainage of segmental grafts of pancreas provides a preparation with intact acinar-islet relationships; the present observations suggest that this may permit longer islet survival in the absence of acinar destruction and subsequent fibrosis. PMID- 2581341 TI - [Cytological analysis of the protein component of the nuclear chromatin in rat sympathetic neurocytes in postnatal ontogeny. I. The age-related changes in the histones detectable by ammoniacal silver and the matrix activity of the chromatin in rat sympathetic neurocytes]. AB - The nuclear histones of the rat superior cervical ganglion neurons were stained at different stages of postnatal ontogenesis with ammoniacal silver (AS). Considerable changes in neuronal staining were revealed during the terminal cytodifferentiation, whereas no changes were found during mature age and in a more advanced age. A combined method was proposed that involved simultaneous AS staining and radioautographical evaluation of transcription in the same cell. No correlation was seen between the nuclear AS-staining and the number of active transcription units. PMID- 2581340 TI - [Ultrastructural changes in thyrocytes exposed to the antithyroid preparations betazin and diiodotyrosine]. AB - Ultrastructure changes in the thyroid gland cells of rats were studied when feeding of bethazine and diiodthyrozine to rats at doses 0.01, 0.1 and 1.0 mg/kg of body's weight for 12 months. The ultrastructure changes in thyrocytes typical both for hyper- and for hypofunction of the gland were revealed. PMID- 2581343 TI - [Mycoplasma contamination of cell cultures: methods for its detection and the possible routes of Mycoplasma infection spread]. AB - 83 continuous cell lines were screened for mycoplasma contamination by three methods: microbiological seeding for enriched media, staining with Hoechst-33258 stain, and autoradiography with 3H-thymidine incorporation. It has been shown that combination of different methods is necessary for the strict control of mycoplasma-contamination in cell cultures. Simultaneous manipulation with mycoplasma infected and pure cell lines leads to cross-contamination in 2-3 passages. Precautions are described to preclude mycoplasma-contamination during prolonged cell cultivation. PMID- 2581342 TI - [Cytological analysis of the protein component of the nuclear chromatin in rat sympathetic neurocytes in postnatal ontogeny. II. The age-related changes in the nonhistone chromosomal proteins detectable by fast green and the matrix activity before and after extraction of the weakly bound fraction]. AB - A cytophotometrical study was made of Fast Green FCF binding by nuclear non histone proteins of the rat superior ganglion neurons at pH 2.6 (1 day, 1 week, 1 and 5 months, and 2.5 years after birth, a. b.). An increased dye binding by fraction NHP, stable in 0.35 M NaCl, was seen during the terminal cytodifferentiation (between days 7 and 14 a. b.). The extraction of a loosely bound fraction of non-histone proteins caused a decrease in the transcription level evaluated by the Moore method, throughout the whole postnatal ontogenesis, and no effect of extraction was noticed in respect of the AS-staining of nuclear histones. PMID- 2581344 TI - [Z-line structure of the rabbit psoas muscle studied by negative contrast staining]. AB - The ultrastructure of the Z-disc of the rabbit psoas muscle was elucidated by electron microscopy using negative staining technique. Conclusions summarized from this work are as follow: (a) Z-disc involves two layers of Z-filaments, i.e. connecting filaments, which bind thin filaments of adjacent I-discs in the Z-line region. These layers are spaced about 380 A apart. (b) Z-filaments measure 380 A X 30 A. (c) The angle between the connecting filaments and the thin filaments depends on ionic conditions and varies from 20 degrees to 90 degrees. (d) We conclude that alpha-actinin is a structural component of Z-filaments, since dimensions of Z-filaments and their interaction with thin filaments are similar to those of alpha-actinin. PMID- 2581346 TI - [Relative spacing of the microtubules and intermediate filaments during fibroblast spreading in culture]. AB - Using double immunofluorescence staining, microtubules and intermediate filaments were shown to have similar distribution in the substrate-spread mouse embryo fibroblasts. However, in cells spreading on the substrate, microtubules grow from the centre to the periphery regions quicker than intermediate filaments. We suppose that microtubules may guide the spreading of intermediate filaments from the perinuclear regions to the periphery of the cell during its spreading. PMID- 2581345 TI - [Immunomodulating effect of cyclophosphane under different modes of administration to mice]. AB - A study was made of the effect of injection of cyclophosphamide (CP) immunomodulating to BALB/c mice, according to 3 schemes of injection with the whole dose being 200 mg/kg. In all, the state of peripheral blood and spleen, the cellular content of lymph nodes and the number of DNA-synthesizing cells in them were studied, in addition to the ability of lymph node lymphocytes to proliferative reaction on T and B cells mitogens in vivo. It was determined that a 2-fold injection of CP, in contrast to 10- and 5-fold injections, resulted in splenomegaly and leukocytosis in the experimental animals. By means of quantitative tests in vivo, in was demonstrated that the dynamics of restoration of proliferative responses to mitogens depends on the CP injection scheme. These tests proved to be more informative for registration of immunomodulating effect of CP, than the study of cellular content of lymph nodes and the number of DNA synthesizing cells in them. PMID- 2581347 TI - [Laryngeal papilloma in children. A review from the County of Funen over a 45 year period]. PMID- 2581348 TI - Tripeptidyl carboxypeptidase activity of angiotensin-converting enzyme in human tissues of the urogenital tract. AB - The tripeptidyl carboxypeptidase activity of angiotensin-converting enzyme (EC 3.4.15.1) has been determined in several human tissues of the urogenital tract. Benzoyl-glycyl-L-seryl-L-prolyl-L-phenylalanine was used as substrate. The cleaved benzoyl-glycine was measured by means of high-performance liquid chromatography. Results obtained showed a high enzymatic activity for seminal plasma, vesicula seminalis and benign prostatic hyperplasia. Normal prostate and in particular prostatic adenocarcinoma have low enzymatic activity. The activity of the enzyme is sensitive to inhibition by the angiotensin-converting enzyme inhibitor captopril. PMID- 2581349 TI - [DNA oriented automated malignancy diagnosis and malignancy grading in prostatic cancer]. AB - 85 patients with prostate cancer and 20 patients with benign prostatic hypertrophy underwent DNA single-cell fluorescence photometry to investigate the possibility of DNA-related automatic diagnosis and grading of prostate cancer. The DNA histograms were analysed statistically by univariate data description, stepwise linear discriminant analysis and regression analysis. The accuracy for the malignancy diagnosis was 85.1%, with 10.6% false-negative and 4.3% false positive results. The accuracy of the malignancy grading, however, was very poor with only 39.5%. PMID- 2581350 TI - [Clinico-immunological study of prostatic adenoma patients]. PMID- 2581351 TI - [Dynamics of the indices of variation pulsimetry in prostatic adenoma patients]. PMID- 2581352 TI - [Medical gymnastics for prostatic adenoma patients]. PMID- 2581353 TI - [Adenocarcinoma of the seminal vesicle]. PMID- 2581354 TI - [Errors, hazards and complications in transurethral operations (prostatic and bladder tumors)]. PMID- 2581355 TI - Symposium regulation of androgen action, Montreal 1984. PMID- 2581356 TI - [Dysuria following transurethral electroresections of adenomas with concomitant prostatitis]. AB - Following transurethral electroresection of prostatic adenomas 31 patients, had persistent postoperative complaints which were difficult to influence by drugs. This was despite the absence residual urine, were due to histologically identified concomitant prostatitis and current-induced damage and could be prevented by open prostatectomy in another 35 patients--even with very small prostatic adenomas. PMID- 2581357 TI - Outbreak of the pigeon paramyxovirus serotype 1 in the Sudan. PMID- 2581358 TI - Monoclonal antibodies directed against Brucella abortus cell surface antigens. AB - A panel of monoclonal antibodies (MAb) has been raised against Brucella abortus cell surface antigens from mice immunized with either heat/phenol treated or UV killed bacterial suspensions of B. abortus. The hybridomas were screened by either a microagglutination procedure or by an indirect enzyme immunoassay (EIA) on sonicated bacterial preparations. From a large number of MAb generated by various procedures, two distinct types of MAb emerged. The most numerous type was capable of agglutinating B. abortus and reacting with a soluble preparation of lipopolysaccharide (LPS). A second type was not capable of agglutinating the bacterial suspensions or of binding to the soluble LPS preparation but reacted with an antigen present in bacterial sonicates. Two MAb of this type react differentially with sonicates prepared from virulent and avirulent strains of B. abortus. There appeared to be sufficient evidence from our analysis of the relative degree of cross reaction with antigens present on a range of B. abortus strains and Brucella and xenogenic bacterial species to conclude that each of the seven MAb was recognising a separate antigenic site on the B. abortus cell surface. PMID- 2581359 TI - Granular cell tumors contain myelin-associated glycoprotein. An immunohistochemical study using Leu 7 monoclonal antibody. AB - An immunohistochemical staining procedure using Leu 7 (HNK-1) monoclonal antibody was used to study the distribution of myelin-associated glycoprotein in granular cell tumours. Positive reactions were noted in 10 of the 13 tumours investigated. This observation supports the concept that granular cell tumours are of Schwann cell origin. PMID- 2581360 TI - Circadian variation in mitotic influx in a keratinized epithelium. The stathmokinetic technique used in vivo on the hamster cheek pouch epithelium and analyzed by periodic regression analysis. AB - An in vivo study of the hamster cheek pouch epithelium using the stathmokinetic technique (Colcemid) demonstrated a circadian variation in mitotic influx. Based on measurements of all nucleated epithelial cells the diurnal mean was estimated in two separate experiments as 0.34%/h +/- 0.02 (SE) and 0.27%/h +/- 0.02 (SE) respectively. 3HTdR was injected in the latter study (a double labelling experiment). The significant difference between the two experiments is, however, probably due to biological variations. The maximal values for the mitotic rate were found during the light (resting) period, as were the maximal values for the mitotic index. The mean mitotic influx for the 'light period' was estimated as 0.5-0.4%/h, and for the 'dark period' as 0.2%/h. Independent analyses demonstrated the necessity of a circadian-dependent correction of the 1 and 4 h values of accumulated metaphases. The 1 h value was significantly too high during the light as well as the dark period. The 4 h value was found to be too low, but only significantly so during the dark period. Basing the estimation of mitotic rate on the 3 h accumulation value produced only very similar results to those found by using all four accumulation periods. The use of overlapping experiments proved that only cells entering mitosis after Colcemid application were arrested, so that when arrested metaphases were counted the accumulation line was correctly drawn through the origin. In the latter study (the double labelling experiment) both S- (Moller and Keiding 1982) and mitotic influx were estimated, the estimates being 0.55%/h +/- 0.03 (SE) and 0.27%/h +/- 0.02 (SE) respectively. Even considering possible methodological problems, the discrepancy between the S efflux and the mitotic influx indicates cell death and/or differentiation from G2. PMID- 2581362 TI - [Hygienic standardization of gases forming after combustion of hydrocarbon fuels]. PMID- 2581361 TI - Localization and distribution of anionic charges in the glomerular mesangium of normal and nephrotic rats. AB - Sulfated glycosaminoglycans and sialoglycoproteins are thought to play a pivotal role in the glomerular capillary wall barrier to filtration since these anionic charged elements are important in the maintenance of capillary wall integrity and constitute a charge-selective filter. The development of proteinuria in puromycin aminonucleoside (PAN) nephrosis is associated with polyanion loss from the glomerular capillary wall structures. Since in PAN nephrosis the permeability of the mesangial area to plasma proteins and tracer substances has also been shown to be increased, the purpose of this study was to analyse the localization and distribution of anionic charges in the glomerular mesangium in this experimental model. Glycosaminoglycans were labeled by perfusion of the kidneys with ruthenium red solution (RR). Electron microscopic examination revealed the presence of distinct small RR granules ("anionic sites") in the mesangial intercellular matrix substance and in the laminae rarae of the glomerular basement membrane (GBM). The center-to-center spacing of the granules was measured and a frequency distribution of intervals in different interval classes was constructed. In normal glomeruli the anionic sites in the mesangial matrix showed a distribution pattern identical to the GBM with a maximal interval incidence at the 31-40 nm class. In nephrotic rats anionic site distributions in matrix and GBM did not change significantly. Sialoglycoproteins were labeled with colloidal iron (CI). In PAN nephrosis a decrease of CI binding was observed at the epithelial-basement membrane junction of the glomerular capillary wall. However, CI labeling of the mesangial matrix and mesangial cell membranes did not differ from that of normal glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581363 TI - [Diagnostic and prognostic value of the determination of cyclic nucleotide levels in disorders of cardiac rhythm]. PMID- 2581364 TI - [Glucocorticoid receptors and the histological structure of breast cancer]. AB - Glucocorticoid receptors (GR) were studied in tumor cytosols from 140 breast cancer patients. The level of GR depended upon tumor histology. The highest GR level was found in medullary cancer, while the lowest--in a mucinous one. The GR level in ductal-invasive cancer was significantly higher than in the lobular infiltrative type. The frequency of GR in tumors of the 1st grade of malignancy was significantly lower than in those of the 2nd and 3rd grade of malignancy. The 1st grade of malignancy tumors which contained GR had estrogen and progesterone receptors, too. The increasing malignancy was matched by the rising percentage of such tumors which was as high as 47% among 3rd grade of malignancy tumors. PMID- 2581365 TI - [Use of HBFP staining for the diagnosis of the degree of contractile structure damage in cardiomyocytes]. PMID- 2581366 TI - [Monoreceptor antibodies to the hemagglutinin antigenic determinants of influenza viruses H2N2 and their virus-neutralizing activity]. PMID- 2581368 TI - [Effect of thymosin on interferon production and antiviral resistance in mice]. AB - The 5th and 6th fractions of thymosin, a hormone of the thymus gland, stimulated interferon production both in vivo (experiments in white and CBA mice) and in vitro in CBA mouse splenocytes when different interferon inducers were used (phage dsRNA, poly(G): poly(C), NDV, and mitogens). The highest stimulating effect in vivo was observed with interferon induction 6-8 hours after thymosin administration. An increase in production of both alpha/beta and gamma interferons under the influence of thymosin was observed. Thymosin alone induced no interferon synthesis. PMID- 2581369 TI - [Stimulating action of calcium chloride on the formation of human immune interferon]. PMID- 2581367 TI - [Matrix protein of the influenza virus: properties, functions and role in the diagnosis of influenza]. PMID- 2581370 TI - [Monoclonal antibodies in virology]. AB - The application of hybridoma technology to the preparation of monoclonal antibodies has had a strong stimulatory effect on many areas of virological research. This development has expanded our knowledge with respect to antigenic variation among viruses and detailed analysis of complex antigenic structures of virus proteins and has also led to the elucidation of the molecular foundations of pathogenesis and virulence in model systems. The practical importance of these results spans many important areas of applied virology such as the development of new viral vaccines, passive immunization and diagnosis of viral infections. PMID- 2581371 TI - [Demonstration of a species specific determinant of Bacteroides fragilis lipopolysaccharides using monoclonal antibodies]. AB - The reactivity of two monoclonal antibodies to Bacteroides fragilis was tested (ELISA) with 37 strains of B. fragilis, 1 strain each of B. thetaiotaomicron, B. ovatus, B. vulgatus and B. eggerthii, 1 strain of Fusobacterium, as well as Pseudomonas aeruginosa (6 strains), E coli (8 strains), Klebsiella (2 strains), Yersinia enterocolitica (1 strain) and LPS from Salmonella minnesota. Both monoclonal antibodies proved to be specific for B. fragilis. The determinants recognized by these antibodies are localized in the LPS of this gram-negative anaerobe. PMID- 2581372 TI - [Localization of functionally important areas of the regulator protein factor H using monoclonal antibodies]. AB - Four monoclonal antibodies to the control protein of the complement system, factor H, were used to try to localize functionally important domains on the molecule. Attempts to inhibit the interaction of C3b and H in ELISA and agglutination assays by means of these monoclonal antibodies showed that two of them, namely MAH 1 and MAH 2, recognized an epitope in close proximity to the binding site for C3b on H. The determinants defined by MAH 3 and MAH 4 are localized at a certain distance from this binding site, the MAH 4 epitope being situated closer to it than the MAH 3 epitope. The cofactor function of H with respect to C3b inactivator was inhibited by the same monoclonal antibodies which interfered with the binding of H to C3b. Since MAH 1, MAH 2, MAH 3 and MAH 4 all bind to the same tryptic 38 KD fragment of H, the binding site for C3b on H, as well as the cofactor activity seem to reside on this fragment. PMID- 2581373 TI - [Tumor serodiagnosis with monoclonal antibodies]. AB - The applicability of monoclonal antibodies (MAb) to the serological diagnosis of solid tumours is discussed. So far test kits with MAb cannot claim higher resolution of specificity as compared with conventional antisera. One approach to solve this problem would be to produce MAb to peptides derived from tumour extracts which are unique to malignant tissue. PMID- 2581374 TI - [10 years of endoscopy at the University Department of Surgery in Graz]. AB - The results of the endoscopies carried out from 1973 to 1983 at our hospital are reported (6947 gastroscopies, 2189 colonoscopies). Gastroscopic aftercare following gastric resection for benign gastric disorders and after partial gastrectomy for carcinoma is discussed. The results of the use of laser in emergency endoscopies are presented (731 patients with 827 bleedings lesions). By implementation of laser there was a remarkable reduction in the rate of immediate and early operation and in early mortality in cases of gastrointestinal bleeding. The results of 244 endoscopic polypectomies are reported. PMID- 2581376 TI - [Special nursing measures in acute disease from the surgeon's viewpoint]. PMID- 2581375 TI - [Changes in the intermediate filament cytoskeleton of liver cells in alcoholic liver injury]. AB - Mallory bodies are a morphological key feature of severe alcoholic liver cell injury (alcoholic hepatitis) and the morphological expression of dysregulation and derangement of the intermediate filament cytoskeleton of the hepatocyte. Their pathogenesis is still unclear. Studies on Mallory body formation may not only help to elucidate the mechanisms of liver cell injury associated with alcoholic hepatitis, but may also contribute to our understanding of the regulation and function of the intermediate filament cytoskeleton. PMID- 2581377 TI - [Stress and the endogenous opioid system. III. Classification of the opioid system in the process of adaptation]. AB - In this article the effects of stress-induced release of opioid peptides are integrated into the local (LAS) and general adaptation (GAS) syndrome. Findings are explained which plead for a participation in the LAS and AAS in the sense of a reserve mechanism for the maintenance of the homoeostasis. Three areas in which these opioid peptides possibly interact are discussed, articularly the adrenal glands because of their possible importance in effectuation of stress processes. Interactions between opioid system and catecholamines as well as of opioid peptides with substance P entitle to classify the opioid system as an effective regulator of biochemical processes in stress. PMID- 2581378 TI - [Effect of low molecular dextran on maternal microrheologic parameters, fetal heart rate and transcutaneous fetal oxygen partial pressure in labor]. AB - The results from animal experimental research have shown that the infusion of dextran 40 increased the uterine blood flow mainly by decreasing the vascular resistance and by this improving the oxygen supply to the fetus. Dextran 40 given in a dosage of 50 ml/min within 10 minutes to 11 pregnant women during parturition showed that the fetal blood PO2 increased if the PO2 before infusion was low and decreased if the PO2 before infusion was high. Therefore the question enhanced if the reduced maternal oxygen capacity results in a reduction of fetal PO2 (tcPo2) too. After informed consent 10 healthy pregnant women at term with a normal pregnancy got an infusion of 500 ml dextran 40 during 30 minutes. The following maternal parameters were measured: heart rate, mean arterial blood pressure, intrauterine pressure and transcutaneous carbon dioxide tension (tcPCO2). Maternal microrheological parameters before and after infusion of dextran 40 were estimated as following: plasma viscosity, erythrocyte aggregation, serum osmolality, colloid osmotic pressure, hemoglobin and haematocrit. The mothers were laying in the side position and their ventilation was controlled by tcPco2 (Drager, Lubeck). The following fetal parameters were registered: basal fetal heart rate, transcutaneous fetal oxygen partial pressure (tcPo2) and the umbilical cord blood gases. After rupture of the fetal membranes and at a cervix dilatation of about 5-7 cm a tcPo2 electrode (Drager, Lubeck) was fixed at the fetal scalp with an acrylate glue (Histoacryl) and by this fetal tcPo2 and its "flow" registered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581379 TI - [Prenatal diagnosis of Meckel-Gruber syndrome]. AB - The Meckel Gruber syndrome can be diagnosed in the 2nd trimester by specific sonografic examinations combined with AFP measurement in serum and amniotic fluid. Since 1977, we have observed nine fetuses showing this syndrome. 4 cases could be diagnosed between the 19th and 24th week of gestation. Giving one case report as an example we would like to illustrate the diagnostic procedure which leads to the diagnosis: Meckel Gruber syndrome. PMID- 2581380 TI - [Prenatal ultrasound findings in Arnold-Chiari deformity]. AB - The Arnold-Chiari malformation is a congenital deformity characterized by displacement of parts of the cerebellum, fourth ventricle, pons and medulla oblongata into the spinal canal. The ACM almost always is associated with a hydrocephalus and a myelomeningocele. The report demonstrates the sonographic findings of a ACM at 20 weeks' gestation. Clinical findings, aetiology and pathogenesis of the malformation are discussed. PMID- 2581381 TI - [Circumscribed palmoplantar keratosis with altered keratohyalin granules. Histological and electron microscopic findings]. PMID- 2581382 TI - [Alpha 1-fetoprotein--a marker of potential PUVA side-effects in psoriasis?]. AB - Serum concentrations of alpha 1-fetoprotein (AFP) during PUVA treatment have been analyzed in 12 patients suffering from severe psoriasis or psoriatic arthritis. The results have been compared with AFP levels in psoriatics without PUVA treatment (group II), patients with psoriatic arthritis treated with methotrexate (group III), as well as dermatological patients without psoriasis (group IV). All groups revealed AFP levels below 25 ng/ml. Although a slight raise of AFP could be observed during PUVA therapy (p less than 0.005), we assume that AFP detection cannot be regarded as a marker of potential PUVA side-effects in psoriasis. PMID- 2581383 TI - [Pharmacology of astemizole (Hismanal) a non-sedating H1 antihistaminic]. AB - In the compound 48/80 lethality test in rats, which is based on the specific activation of mast cells, astemizole was found to be a potent, long-acting and orally very effective inhibitor of anaphylactoid shock. In comparison to other histamine-H1 antagonists, astemizole was remarkably free of interactions with muscarine, serotonin, dopamine, noradrenaline and opiate receptors, and devoid of effects on normal body functions. No evidence of central effects was found, and astemizole did not change the intensity of action of several centrally acting drugs. Toxicity studies have shown astemizole to be a very safe drug. Astemizole is a very effective inhibitor of allergic reactions in rats and dogs. The low oral therapeutic doses of astemizole are expected to provide a pronounced and long-lasting inhibition of allergic reactions in the absence of side effects. PMID- 2581384 TI - [Significance of histamine in immediate allergic reactions]. AB - Histamine has generally been accepted to be an important mediator of immediate type-allergic reactions. Histamine is released from antigen-induced sensitized mast cells and basophils. Histamine acts on its effector cells via specific H1 and H2-receptors. The stimulation of the H1-receptor type results in a contraction of smooth muscle cells of the gastrointestinal tract, the bronchioli and the large blood vessels. In addition, there are increased vascular permeability and dilation of small blood vessels. Activation of nasal exocrine glands is also due to the H1-receptor. The main effects of H2-receptor activation results in gastric acid secretion and dilation of small blood vessels. The effects of histamine are inhibited by specific H1-and H2-antagonists. PMID- 2581385 TI - [Tachycardias caused by double ventricular responses and unusual atrioventrio ventricular relations in linear dissociation of the AV node]. AB - Noninvasive recordings in a 69-year-old woman showed phasic shifts between two distinct PR intervals of about 0.21 and 0.58 s suggestive of dual AV nodal conduction in the presence of two intranodal pathways. Episodes of tachycardia exhibited a one to two relationship between P waves and QRS complexes, with the same short and long PR intervals interpreted as simultaneous anterograde fast and slow conduction via the two AV nodal pathways, leading to a double ventricular response to single P waves. Various mechanisms of transition from short to long or long to short conduction times and concealed conduction phenomena could be demonstrated supporting the concept of two functionally separated intranodal pathways. PMID- 2581386 TI - In vitro cellular muscle calcium metabolism. Characterization of effects of 1,25 dihydroxy-vitamin D3 and 25-hydroxy-vitamin D3. AB - Cultures of vitamin D-deficient chick soleus muscle and 12 day-old chick embryo myoblasts were used to characterize the effects of 1,25-dihydroxy-vitamin D3 and 25-hydroxy-vitamin D3 on muscle cell Ca metabolism. Physiological amounts of both sterols increased the rate and extent of 45Ca uptake by cultures. However, 1,25(OH)2D3 was significantly more effective than 25 OHD3. The greater potency of 1,25(OH)2D3 to increase Ca uptake could be shown after various treatment intervals of cultures and using a wide concentration range of both derivatives. Information about Ca pools affected by vitamin D3 metabolites was obtained through kinetic analysis of Ca efflux in cultured myoblasts. Cytoplasmic and mitochondria Ca pools were identified on the basis of their half-times of desaturation and by selective inhibition of plasma membrane and mitochondrial Ca transport with LaCl3 and Ruthenium Red, respectively. The data suggests that 1,25(OH)2D3 acts on muscle cellular Ca by increasing Ca efflux and influx through mitochondrial and plasma membranes whereas the predominant effect of 25 OHD3 is to increase Ca influx into mitochondria. PMID- 2581387 TI - Isolation of populations of antipeptide antibodies directed against different epitopes of the same fragment. AB - Rabbit antibodies against small peptides may be composed by subpopulations recognizing different epitopes made likely by few amino acids. This explains the frequent crossreactivity of antipeptide antibodies with unrelated peptides. A suitable use of immunoadsorbents is suggested to obtain truly specific antibodies able to react with restricted amino acid sequences. PMID- 2581388 TI - Antigenic analysis of Trypanosoma cruzi strains by crossed immunoelectrophoresis: demonstration and isolation of antigens particular to some strains. AB - Antigenic differences among soluble extracts of Y, CL, SF, and Colombian strain epimastigotes of Trypanosoma cruzi have been demonstrated by crossed immunoelectrophoresis with an intermediate gel containing the heterologous antiserum. Using crossed immunoelectrophoresis with the homologous antiserum, over 30 precipitin lines could be demonstrated for each strain and, even though marked differences were observed in experimental infections, the strains shared a significant number of antigens. In addition, some strain-particular antigens were isolated using affinity chromatography. These antigens could be valuable in the study of biological, immunological, and pathological characteristics of experimental and natural T. cruzi infections. PMID- 2581389 TI - X-ray sensitivity and DNA synthesis in synchronous culture of Plasmodium falciparum. AB - The relationship between parasite development and sensitivity to irradiation with X-rays was investigated during a single synchronous cycle of Plasmodium falciparum in culture. The sensitivity of the parasites to irradiation was closely correlated with the phases of DNA synthesis. Their sensitivity was greatest at the ring stage in development, but decreased at the trophozoite stage when DNA synthesis begins. Lowest sensitivity was found when DNA synthesis was most rapid as the parasites were transforming from late trophozoite to schizont forms. These findings suggest that DNA is the target of the lethal radiation damage in the parasites. PMID- 2581390 TI - Search for shared antigens in the schistosome-snail combination Trichobilharzia ocellata-Lymnaea stagnalis. AB - Mother and daughter sporocysts of Tricholbilharzia ocellata, developing in the snail host Lymnaea stagnalis, were searched for substances with antigenic similarities to the snail's haemolymph. Antisera to cell-free snail haemolymph and fractions thereof were used in three different immunocytochemical staining methods, applied on sections of parasitized snails. Snail tissue was consistently stained; cercariae were stained, indicating that the applied methods were successful. Most sections through mother and daughter sporocysts were completely unstained. It is concluded that neither mother nor daughter sporocysts are masked by the antigens studied or substances mimicking these. The relevance of the present observations is discussed. PMID- 2581391 TI - Cancer trends: brachytherapy. PMID- 2581393 TI - [Tumor marker diagnosis in non-seminomatous testicular tumors using human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP)]. AB - In 28 patients with non-seminomatous testicle tumour the tumour markers human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) were determined radioimmunologically and enzymeimmunologically, respectively. While tumours with chorionic carcinoma (n = 8) always were marker-positive, in the embryonic carcinoma in 2 out of 10 cases falsely negative findings appeared. On 5 patients the biochemical monitoring of the course of the testicle tumour disease is demonstrated in detail by means of HCG and AFP and estimated as very helpful method. Advantages and problems of the marker diagnostics are shown and discussed. The positive marker findings were absolutely evident for a metastasation. On the other hand, marker negativation was not always to be equated with absence of a tumour and demanded a further control of the patient by means of all other available methods of diagnostics up to the second-look operation. PMID- 2581392 TI - Rat alpha 1 macroglobulin inhibits hemagglutination by influenza C virus. AB - Purified alpha 1-macroglobulin (RMG) isolated from rat plasma was found to be a potent inhibitor of hemagglutination by influenza C virus. Neuraminidase treatment of purified RMG reduced its inhibitory activity by more than 80% indicating that sialic acid is required for maximal HI-activity. The inhibitory activity of RMG was shown to be sensitive to the receptor-destroying activity (RDA) of influenza C virus. Methylation analysis of the glycopeptides of RMG indicated the presence of only one major type of oligosaccharide which is a complex N-linked oligosaccharide with a biantennary structure. Comparison of the glycopeptides before and after neuraminidase treatment revealed that the oligosaccharides are terminated by sialic acid residues attached to galactose residues at position C-6. Methylation analysis was also performed on RMG which had lost its inhibitory activity upon incubation with RDA of influenza C virus. No difference between the glycopeptides of native and inactive RMG could be detected. Galactose was found to be substituted at position C-6 in both samples, indicating that also the oligosaccharides of inactive RMG are terminated by sialic acid. The implications of these results are discussed. PMID- 2581395 TI - [Intrahepatic cholestasis in hormonal contraception--a case with a difficult and expensive differential diagnosis]. AB - Reported is a case of serious intrahepatic cholestasis after a two month's medication of 2 mg chlormadinonacetate/0,08 mg mestranol (Ovosiston). PMID- 2581394 TI - [Persistent virus infections and their sequelae]. AB - Besides acute virus diseases, persistent virus infections have attracted increasing attention during the last few years. In the case of such infections, the infecting virus may remain in the host organism for months or even years, before symptoms appear. These persistent virus infections can be caused by different viruses and may lead to a variety of pathogenic reactions and clinical manifestations. As far as knowledge goes, the mechanisms underlying a virus persistance are equally different. Within the space limitations, an attempt is made to present such mechanisms and to derive from them the pathogenesis of the follow-up diseases. PMID- 2581396 TI - Demonstration of keratinizing effect of n-butyrate on day-old chicken crop epithelium. PMID- 2581397 TI - [Serum proteins of worm-infested deer (Capreolus capreolus L. 1758). Comparison between ordinary and immunoelectrophoresis]. PMID- 2581398 TI - [Correlation between the ipsi- and contralaterally directed nerve fibers from the C2 zone of the rat cerebral cortex]. AB - On frontal sections of the brain of albino rats, by means of peroxidase technique, studies have been made on peculiarities of distribution of cortical nervous fibers from somatosensory zone C2 in fugal and comissural directions. Horseradish peroxidase was administered electrophoretically in the focus of the response to electrical stimulation of the distal part of contralateral forelimb of the animal. The data obtained were compared with the results of the distribution of labeled fibers from other, more lateral and medial zones. Single retrogradely labeled cells in symmetrical (with respect to peroxidase application zones) C2 areas of contralateral hemisphere were found indicating the existence of single comissural connections between these parts of the brain cortex. It was established that among anterogradely labeled fibers emerging from the label zone in the focus of the response, comissural ones constitute 34-44%, whereas among fibers from the same zone outside the response focus their share increases up to 52-55%. PMID- 2581399 TI - [Phase cultivation of microorganisms]. PMID- 2581401 TI - [Basic somatic antigen or antigen obtained from Yersinia pestis by the Boivin Mesrobeanu method]. PMID- 2581400 TI - [Mapping of the genetic determinant controlling Salmonella K-antigen synthesis. II. Nonmotile mutants of Salmonella typhimurium]. AB - According to the preliminary data, S. typhimurium K-antigen is located in the area of minutes 40-44 on the Salmonella chromosome map. The formation of nonmotile mutants from motile Salmonella strains was induced by the action of nitrosoguanidine. Two main groups of mutants differing in their reaction of agglutination with H- and K-antisera were obtained: Mot-H-K- (motA or motB mutants) and Mot-H-K- (H1- or fla- mutants). The transduction transfer of the sign of motility by phage P22HT to H-K- mutants and to H1- and flaE- mutants led to the restoration of agglutination ability with respect to H- and K-antisera in all Mot+ transductants under study simultaneously. The restoration of H+K+ phenotype was also observed in spontaneous motile revertants obtained from H-K- mutants. Thus, the gene controlling the synthesis of K-antigen in Salmonellae was shown to be incorporated into the Fla operon, the regulatory system of the operon controlling the expression of this gene. PMID- 2581403 TI - [Cytotoxic action of the interferons produced by the cells of newborn and sexually mature animals]. AB - The results of investigations produced in newborn and adult animals revealed age related differences in the activity of lactate dehydrogenase and its isoenzyme fractions. An increase in the total lactate dehydrogenase activity was observed in both cases, the maximum activity being achieved on the third day of observation. Besides, after the introduction of interferon from newborn animals an increase in the activity of fraction LDH-2 was observed, while the introduction of interferon from adult animals produced an increase in the activity of fraction LDH-5. PMID- 2581402 TI - [Isolation and evaluation of the specificity of an antiserum to the thymic polypeptide factor]. AB - The specificity of antisera, obtained by the immunization of rabbits with the conjugated antigenic preparations of the thymic factor, have been evaluated by the method of immunochemical analysis. To carry out the comparative study, polypeptides isolated from the pineal body, cortex and white matter of the brain, Thy-1 antigen from the cerebral cortex and insulin have been used. The polypeptides of the thymus and the brain have been found to differ in their amino acid composition and molecular weight. The thymic factor possesses specific antigenic determinants which are absent in the tested preparations of cerebral polypeptides and insulin. The rabbit antisera obtained in this investigation are highly specific and can be used for the immunochemical determination of the thymic factor in the blood and other biological fluids. PMID- 2581405 TI - [Neurotransmitters in Huntington chorea (review)]. PMID- 2581404 TI - [Role of neurotrophic control in the formation of vertebrogenic neural and myodystrophic syndromes]. AB - The authors performed pathomorphological examinations in 19 patients with compressional-neural and myodystrophic syndromes of lumbar osteochondritis and also in 16 experimental animals with an impaired axoplasmic current. In the light of the modern understanding of the neurodystrophic control the authors discuss the mechanisms of the denervational-reinnervational process in muscles of patients with vertebrogenic pathology and myodystrophic disorders. PMID- 2581407 TI - Reconstructive operations of combined laryngeal and tracheal disorders. PMID- 2581406 TI - [Energetic role of the plasma and mitochondrial membranes of neurons in antenatal pathology with increased convulsive susceptibility (review)]. PMID- 2581408 TI - Reconstruction of the jaws with pedicle bone grafts. PMID- 2581409 TI - The tensor fasciae latae musculocutaneous flap in operations for trochanteric decubitus ulcers. PMID- 2581410 TI - Volkmann's ischaemic contracture. PMID- 2581411 TI - Loss injuries of the fingers. PMID- 2581412 TI - Treatment of keloid scars. PMID- 2581413 TI - Basophil histamine release in asthma patients after in vitro provocation with Althesin and etomidate. AB - Our aim was to compare the histamine-releasing effect of etomidate and Althesin on basophil leukocytes from asthmatic patients and normal persons. Blood from eight asthmatic patients and six normal persons was tested for histamine release after in vitro provocation with etomidate and althesin. In the group of asthmatic patients there was a significantly higher histamine release after provocation with althesin than after provocation with etomidate at all concentrations (P less than 0.05, P less than 0.01, P less than 0.02). There was significantly higher histamine release for asthmatic patients than for normal persons after provocation with althesin at all concentrations (P less than 0.05, P less than 0.01, P less than 0.02). There was no difference between the asthma group and the normal group after provocation with etomidate. Data were analysed using Wilcoxon's and Mann-Whitney's rank sum tests. We conclude that asthmatic patients may risk bronchospasm during induction of anaesthesia with althesin, and that etomidate may be suitable intravenous anaesthetic for asthmatic patients. PMID- 2581414 TI - The effect of myelin basic protein on the protease inhibitors alpha 1 antitrypsin and alpha 2 macroglobulin. AB - The effect of myelin basic protein (MBP) of central nervous tissue on the protease inhibitors, alpha 1 antitrypsin (a1AT) and alpha 2 macroglobulin (a2M) was studied in vitro. For this purpose, 2 characteristics of the protease inhibitors were used, viz. their pattern after isoelectric focusing and their trypsin-binding capacity. Both features of purified a2AT disappeared in the presence of MBP. The tests with a2M revealed that the formation and stability of the complex between a2M and protease were reduced. The results of this study suggest that MBP causes an increase in proteolytic activity by inactivating protease inhibitors. The potential relevance of these results for demyelinating processes in man and animal is discussed. PMID- 2581416 TI - Ionic transport across corneal endothelium. AB - The active potential difference across bovine corneal endothelium was measured in vitro at different temperatures, pH, osmolality and salt compositions. The measurements were made using either identical or different solutions on each side of the membrane. The experimental results are consistent with a model in which sodium is actively transported into the intercellular cleft. We propose that Na+ re-enters the cell electroneutrally by coupled co-transport with carbonate, derived from bicarbonate in the solution. PMID- 2581417 TI - Connections between the sensory retina and the retinal pigment epithelium. AB - The study reports on the presence of connections between the visual receptor outer segments and the apical villi on the retinal pigment epithelium in the human eye. The mechanisms underlying sensory retinal adhesion to the pigment epithelium, recognition and attachment of visual receptor outer segments to the pigment epithelium during phagocytosis, and communication and transport of substances between the two layers of retina have been difficult to define, and molecular connections between the two layers of retina could play an important role in these processes. PMID- 2581415 TI - Alzheimer paired helical filaments: cross-reacting polypeptide/s normally present in brain. AB - Antisera to microtubule-enriched fraction from normal human brain (anti-MT sera) label neurofibrillary tangles and neurites of neuritic (senile) plaques in brain sections of cases with Alzheimer disease/senile dementia of the Alzheimer type (AD/SDAT); the plaque core amyloid is not labeled. These anti-MT sera label both tangles in tissue sections and smears of isolated tangles which had been extracted with sodium dodecyl sulfate (SDS) to remove impurities trapped in between the paired helical filaments (PHF). The tangle labeling of anti-MT sera is eliminated on their absorption both with microtubule-enriched fractions from human and animal brain and with the isolated PHF. Neurofilament triplet, actin, myosin, keratin, or fibroblasts do not absorb the tangles staining antibodies. Furthermore, antisera containing antibodies to tubulin, microtubule-associated high mol. wt. polypeptides (MAPS), neurofilament triplet, and the 50,000 mol. wt. contaminant of CNS neurofilament preparations do not label tangles. On immunoblots of SDS-polyacrylamide gels of isolated PHF anti-MT sera label some of the same polypeptides identified with antisera to PHF; affinity-purified antibodies to tubulin used as a control do not label any PHF polypeptide on the immunoblots. The anti-MT sera, when preabsorbed with the PHF polypeptides eluted from SDS-polyacrylamide gels, do not label tangles. These studies demonstrate that a polypeptide/s cross-reactive with Alzheimer PHF is indeed normally present in brain and that it is different from tubulin, neurofilament triplet, actin, myosin, vimentin, and keratin. PMID- 2581418 TI - Histochemical analysis of secretory vesicles in nongoblet conjunctival epithelial cells. AB - An Alcian-blue/Periodic acid Schiff reagent (AB/PAS) pH dependent staining method was used to identify the mucus content of secretory vesicles of non-goblet epithelial cells of the human conjunctiva. Twenty subjects were selected for biopsy of the midcentral upper tarsal conjunctiva: 10 subjects had no contact lens wearing experience, and 10 subjects wore contact lenses. Human respiratory epithelium was used as a control for the staining procedure. Four-micron paraffin sections of conjunctival and control tissues were stained with Alcian blue at pH 2.5 and 1.0 and counterstained with PAS. Non-goblet epithelial cell secretory vesicles contained neutral mucin, sialmucin, and sulphomucin. This study provides evidence for a 'second' mucus system of the conjunctiva, that this system is in the non-goblet epithelial cells, and that the mucus of this system has sulphomucins, sialomucins and neutral mucins. PMID- 2581419 TI - Effects of light and BAY K 8644, a new 1,4-dihydropyridine, on mechanical responses of rat thoracic aorta. AB - The effect of day light and ultraviolet radiation (360 nm) on mechanical responses to BAY K 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(-2 trifluoromethylphenyl)-py ridine- 5 -carboxylate), potassium (K+) and noradrenaline (NA) of rat aorta rings was investigated. The contractile response to BAY K 8644 (10(-6)M) obtained before and after exposure of the BAY K 8644 stock solution to ultraviolet radiation was unchanged and equal to that of K+, 125 mM. Ultraviolet radiation and day light did not affect responses evoked by K+ (125 mM) and NA (1.8 X 10(-5)M). In contrast to this both types of light relaxed vessels contracted by BAY K 8644 (10(-6)M). The light induced relaxations were reversible, unaffected by addition of propranolol (3 X 10(-6)M) and could not be eliminated by washing the preparations repeatedly with Krebs solution. In vessels contracted by K+ (125 mM) and NA (1.8 X 10(-5)M) ultraviolet radiation induced a reversible relaxation in the presence of BAY K 8644. BAY K 8644 (10(-4)M) and nifedipine (10(-8)M) relaxed preparations contracted by K+. Nifedipine (10(-6)M) totally relaxed preparations contracted by BAY K 8644 (10(-6)M). Ultraviolet radiation eliminated the relaxant effect of nifedipine and decreased the relaxant effect of BAY K 8644 (10(-4)M). The results indicate that BAY K 8644 is more light-stable than nifedipine and that BAY K 8644 sensitized the vascular smooth muscle to ultraviolet radiation as well as day light. Consequently this should be taken into account when BAY K 8644 is studied. PMID- 2581420 TI - Preparation and characterization of myosin from cultured cells of Escherichia coli (02:K1 30156 strain). AB - In this study the myosin preparations isolated from E. Coli cell cultures were analysed. The isolation of myosin from fresh cultures resulted in a substantially higher (approximately 10-fold) yield than from stored cells. The coli myosin, despite the two DEAE-cellulose treatments, contained more RNA and P-lipid than the myosin prepared from skeletal muscle. The RNA content can be removed gradually by acetone denaturation and lipid removal followed by subsequent washings. The fresh preparations contained protein-bound alkali-stable P; part of this was released by Cu ions. The coli myosin can be phosphorylated. The phosphate uptake depended on the concentrations of ATP and Mg2+ and on the time of incubation. The alkaline hydrolysate of the phosphorylated, washed lipid-free preparation was resolved into 8 P-containing peaks on ion-exchange chromatography. Of fractions P-Arg, Pi, P-Lys and 2 P-His conformer were identified by means of synthetic compounds, elution pattern and specific reactions. The remaining compounds could not be identified. The most abundant component was P-Arg suggesting that this compound might play an important role in the cytokinetic movements of E. coli. PMID- 2581421 TI - Cardiac performance in hyperthyroidism assessed by systolic time intervals and radionuclide ventriculography. AB - Systolic time intervals (STI) and radionuclide ventriculography (RNV) were used in the assessment of cardiac performance in 22 patients with hyperthyroidism before and after antithyroid treatment. STI as well as RNV showed enhanced myocardial contractility which was normalized after antithyroid treatment. Beta blocker treatment did not influence the hypercontractility in hyperthyroidism. This implies that beta-blockers alone cannot be regarded as satisfactory long term treatment and that mechanisms other than increased sympathoadrenal drive are involved in the hypercontractility in hyperthyroidism. RNV suggested valvular regurgitation, probably of the mitral valve, in 11 patients. Possible hemodynamic consequences are discussed. PMID- 2581422 TI - Immunological abnormalities in massive cutaneous hyalinosis. AB - Immunological studies in a patient with massive cutaneous hyalinosis, a disease characterized by principally dermal and subcutaneous accumulations of monoclonal kappa light chains and a gliadin-binding mannose-rich 90 kD glycoprotein, show that the ratio of helper to suppressor T cells is decreased and the proliferative responses of the peripheral mononuclear cells to T cell and T cell-dependent B cell mitogens are depressed. High levels of circulating immune complexes were demonstrated by C1q-binding and rheumatoid factor enzyme linked immunoassays. IgM and IgA class antibodies against the hyalin components, the mannosyl-90 kD glycoprotein and type I collagen, and against keratin and gluten were present in high titres. The reactivity of mononuclear cells to phytohemagglutinin normalized and the antibody levels to hyalin proteins, keratin and gluten fell during low dose steroid therapy. However, the concanavalin A response was not reversed, neither did the levels of circulating immune complexes and anti-intercellular substance antibodies decrease. The results demonstrate a very complex dysfunction of the immune system in massive cutaneous hyalinosis. PMID- 2581423 TI - Cancer metastasis: experimental approaches, theoretical concepts, and impacts for treatment strategies. AB - It has been the purpose of this article to describe recent advances in cancer metastasis research. Clinical realities and experimental approaches to the study of underlying basic mechanisms of metastasis formation were discussed. Wherever possible, results were reported which led to the development of theoretical concepts. Such results and concepts were finally evaluated in light of their possible impact for the design of new treatment strategies. Experimental findings from many diverse research fields were summarized with the help of tables, figures, and references. It was concluded that the process of metastasis is a dynamic event that can be described as a sequence of interrelated steps. Experimental results indicated that malignant cells that migrate and disseminate from the primary organ to distant sites and there eventually develop into metastases have to survive a series of potentially lethal interactions. Intimate tumor-host interactions were reported to take place all along the metastatic process. They were elucidated at the steps of angiogenesis, invasion, organ interaction, dormancy, tumor rejection, and tumor immune escape. The outcome of such tumor-host interactions seemed to depend on intrinsic properties of the tumor cells themselves as well as on the responsiveness of the host. Metastasis does not appear as a merely random process. Both clinical and experimental studies revealed that the whole process can be described more appropriately in terms of stochastic, sequential, and selective events, each of which is controlled and influenced by a number of mechanisms. With regard to therapeutic intervention, a selective event offers more possibilities than a random one because it is governed by rules that can be exploited experimentally. Various impacts from experimental studies for the design of antimetastatic cancer treatment strategies were discussed. Sequential steps of the metastatic cascade could become new therapy targets. Conventional empirically derived treatment modalities should become flanked by methods aimed more specifically at critical steps of cancer spread in order to prevent progression of the disease. This is where basic research on mechanisms could make significant contributions to therapy planning in the future. Furthermore, possible negative effects of surgery, radiotherapy, and adjuvant chemotherapy or immunotherapy that could result in enhancement of metastatic progression need to be critically evaluated to limit them as much as possible.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2581424 TI - Tumor angiogenesis. AB - The hypothesis that tumors are angiogenesis dependent has, in the past decade, generated new investigations designed to elucidate the mechanism of angiogenesis itself. Many laboratories are now engaged in this pursuit. Some are studying angiogenesis that occurs in physiological situations, whereas others are interested in angiogenesis that dominates pathological conditions. These efforts have led to (1) the development of bioassays for angiogenesis; (2) the partial purification and, in one case, the complete purification of angiogenic factors from neoplastic and non-neoplastic cells; (3) the development of new polymer technology for the sustained release of these factors and other macromolecules in vivo; (4) the cloning and long-term culture of capillary endothelial cells; (5) the demonstration of the role of nonendothelial cells, such as mast cells in modulating angiogenesis; (6) the discovery of angiogenesis inhibitors; and (7) the demonstration that certain animal tumors will regress when angiogenesis is inhibited. The effects of angiogenesis inhibitors provide perhaps the most compelling evidence for the role of angiogenesis in tumor growth. It is conceivable that the original effort to understand the role of angiogenesis in tumor growth will also lead to the use of angiogenesis inhibitors as a new class of pharmacologic agents in a variety of non-neoplastic diseases such as arthritis, psoriasis, and ocular neovascularization. However, much work remains to be done before it will be possible to understand (1) the regulatory systems that govern capillary density in normal tissues; (2) the factors that maintain the viability of microvascular endothelium; (3) the development of the vascular system itself; and (4) the mechanism by which vascular regression occurs, both in the embryo and in the postnatal organism. A knowledge of the mechanisms which underlie these normal processes may help to enlarge our comprehension of tumor angiogenesis. PMID- 2581425 TI - [Histochemical characterization of different tissue enzymes in prostate adenomas and carcinomas]. PMID- 2581426 TI - [Clinical evaluation of surgical treatment for benign prostatic hypertrophy]. AB - Prostatectomy was performed on 300 patients at our Hospital for the period of 5 years from January 1978 to December 1982. Among those cases, clinical evaluation was made on 290 patients whose medical records were available. Ages of the subjects ranged from 53 to 92 years with an average age at 71.6. Retropubic prostatectomy (RPP) was performed on 81 cases, and suprapubic prostatectomy (SPP) and transurethral resection of prostate (TUR) on 39 and 170 cases, respectively. Surgery was made on 206 cases under epidural anesthesia, 82 cases under spinal anesthesia, and 2 cases under general anesthesia. Preoperative laboratory tests showed abnormalities in 62% of the total. The most frequent preoperative complications were circulatory abnormality and urinary tract infection. Average surgical time was 78.6 min. for RPP, 69.8 min. for SPP, and 76.9 min. for TUR. Average blood volume transfused during operation was 446.3 ml for RPP, 430.8 ml for SPP, and 80.7 ml for TUR. Average period of catheter retention after surgery was 9.2 days for RPP, 10.1 days for SPP, and 4.9 days for TUR. Average postoperative admission period was 18.6 days for RPP, 20.6 days for SPP, and 14.1 days for TUR. Average weight of the isolated adenoma was 41.8 g for RPP, 30.2 g for SPP, 11.5 g for TUR. Postoperative complications such as epididymitis, traumatic infection, and hepatic dysfunction were often found. Latent prostatic carcinoma found in the isolated adenoma was found in 11 cases (3.8%). The presence of anomalies in preoperative laboratory findings did not influence the frequency of postoperative complications. PMID- 2581428 TI - [Clinical evaluation of Cernilton on benign prostatic hyperplasia]. AB - Twenty-two patients whose average age was 67 years and who had benign prostatic hyperplasia of stage I and II were treated with Cernilton for more than 4 weeks. Subjective symptoms were excellently improved and the improvement rate was over 85% in all of the evaluated symptoms of dysuria. In the overall evaluation, 18 out of 22 patients were rated as moderately improved or better, 2 were slightly improved and 2 remained unaltered. Aggravation of the symptoms was found in none of the patients. Objective findings such as residual urine volume and urinary flow rate were improved in 3 patients, although the shrinkage of the prostate was not observed on rectal palpation, retrograde urethro cystography or transrectal ultrasonography. No adverse reaction was observed during Cernilton therapy. In conclusion, it is suggested that Cernilton may be effective and safe for the conservative treatment of patients with early stage prostatic hyperplasia of non surgical indication. PMID- 2581427 TI - [The clinical evaluation of hochuekkito for symptoms of malignant neoplasm patients]. AB - Hochuekkito was administered in 2.5 g doses three times a day to 162 patients who complained of anorexia or lassitude because of genitourinary cancer. The efficacy rate was 63.0%. The rate of effectiveness on anorexia was 48.4% and that on lassitude was 36.6%. Side effects were observed in 12 patients (7.4%), but most of them were mild gastrointestinal disorders. No severe adverse effects were noted. PMID- 2581429 TI - [The histochemistry of complex carbohydrates in the prostatic tumor]. AB - Seventy five prostatic specimens from cancer, BPH and normal controls were studied by light microscopic histochemical methods for the demonstration of complex carbohydrates and some proteins: 1) alcian blue (AB) (pH 1.0), 2) alcian blue (AB) (pH 2.5), 3) Periodic Acid-Schiff (PAS), 4) peroxidase labelled-Ricinus communis agglutinin-diaminobenzidine (PO-RCA-DAB), 5) Concanavalin A-peroxidase diaminobenzidine (ConA-PO-DAB), 6) ConA-PO-DAB-periodic acid-m-aminophenol Fast black salt K (ConA-PO-DAB-PA-AP-FBK). For identifying individual acidic and neutral carbohydrates, following procedures of enzyme digestion were performed upon some tissue sections prior to the above histochemical staining: a) sialidase (prior to staining with AB at pH 2.5), b) streptomyces hyaluronidase (prior to staining with AB at pH 2.5), c) testicular hyaluronidase (prior to staining with AB at pH 1.0 or pH 2.5), d) chondroitinase ABC (prior to staining with AB at pH 1.0 or pH 2.5), e) chondroitinase AC (prior to staining with AB at pH 1.0 or pH 2.5), f) alpha-amylase (prior to staining with PAS). In addition, the tissue specimens from prostatic cancer were stained immunohistochemically for demonstration of prostatic acid phosphatase (PAP) and the serum PAP levels were also measured by radioimmunoassay. The histochemical differences in the prostatic tissue among normal control, BPH and cancer as follows. In the tissue of prostatic cancer, chondroitin sulfate A, C and hyaluronic acid were present in the interstitium. Chondroitin sulfate, hyaluronic acid and sialic acid were present in the cytoplasm of cancer cells. In the tissue of BPH chondroitin sulfate B and hyaluronic acid was present in the interstitium and hyaluronic acid was present in the cytoplasm of epitherial cells. In the epithelial basement membrane of the tissue from BPH, chondroitin B and hyaluronic acid were present. 1,2-Glycol groups of neutral complex carbohydrates in the interstitium of prostatic cancer were shown to exist in smaller amounts than in that of BPH. In the cytoplasm of cancer cells the intensity of both PO-RCA-DAB and ConA-PO-DAB staining could be divided into three groups: strong, moderate and weak. In the prostatic cancer there was a good correlation between the intensity of PO-RCA-DAB staining and tumor grade, and intensity of ConA-PO-DAB staining was correlated well with serum PAP level. The cytoplasm of cancer cells showed a positive reaction to PAP immunostaining and no appreciable difference was observed according to tumor grade.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2581430 TI - [Effect of anticancer agents on rat prostate. Evaluation of organ weight, histological finding and 5 alpha-reductase activities]. AB - To evaluate the effect of anticancer chemotherapeutic antigens on rat prostate, ten kinds of anticancer agents corresponding to the dose generally used for humans were intraperitoneally injected to 63-day-old Wistar rats. The anticancer agents were administered as follows: Cyclophosphamide (CPM) was used at the dose of 8 mg/kg for 7 days. Methotrexate (MTX), actinomycin-D (ACD) and cis-platinum (CDDP), 163 micrograms/kg, 8 micrograms/kg and 833 micrograms/kg for 5 days, respectively. Nitrogen mustard (NM), bleomycin (BLM), peplomycin (PLM), adriamycin (ADM), vincristine (VCR), and vinblastine (VBL), 500 micrograms/kg, 250 micrograms/kg, 170 micrograms/kg, 2.5 mg/kg, 33 micrograms/kg and 83 micrograms/kg, twice in a week, respectively. The rats were killed on the fifth day after completion of the schedule. Then, the weight of the body, the prostate, the epididymis and the adrenal gland were measured. In addition, 5 alpha reductase activities and histological findings in the prostate were examined. For determination of 5 alpha-reductase activities, cell-free homogenate obtained from the rat ventral prostate was incubated with C14-testosterone at 37 degrees C for 30 minutes in an atmosphere of 95% of O2 and 5% of CO2. Subsequently, the metabolites from testosterone were separated and purified with thin layer chromatography using the solvent system with benzene acetone, 4:1 (v/v). 5 alpha Reductase activity was determined with the sum of dihydrotestosterone (DHT) and androstanediol converted from testosterone and indicated as pmol product/mg protein. The 5 alpha-reductase activity was employed as a biological marker for the degree of androgenic dependency in the prostate. The results were summarized as follows. CDDP significantly reduced the weight of the body (p less than 0.001, n = 7), but not the activity of 5 alpha-reductase. NM and VBL had a specific action to reduce the weight of the prostate (p less than 0.01, n = 8) without causing loss of body weight. NM and VBL showed no influence on 5 alpha-reductase activities. The activity of 5 alpha-reductase was markedly damaged by BLM (p less than 0.05, n = 6) and PLM (p less than 0.05, n = 5). However no significant reduction was recognized in the weight of the body and the prostate. CPM, MTX, ACD, ADM and VCR were ineffectual on the body and the prostate weight and 5 alpha reductase activities. In the histological examination, atrophy and degeneration of the glandular epithelium were revealed in the prostate treated with NM, VBL and CDDP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2581432 TI - [Experiments on the production of monoclonal antibodies against lymphocyte antigens in cattle with enzootic cattle leukosis]. AB - Hybridomas were produced which secrete antibodies against cell surface antigens of neoplastic bovine lymphocytes. The monoclonal antibodies of three hybridomas react only with leukemic cells but not with other tested cellular and soluble antigens. Four hybridomas secrete antibodies which probably recognize virus encoded structures on outer membranes of leukemic cells. PMID- 2581431 TI - Presence of acid-labile interferon in the serum of sarcoidosis patients. PMID- 2581433 TI - Hydatidiform moles. AB - This gestational neoplasm arises from the trophoblast, the ectodermal layer of a fertilized ovum. Although benign, hydatidiform moles have the potential to progress to malignant trophoblastic disease. Molar pregnancy must be recognized promptly. The clinical presentation is usually vaginal bleeding, which may contain characteristic tissues. Diagnosis is confirmed by identification of hydropic avascular villi obtained by evacuation of uterine contents. The beta subunit of human chorionic gonadotropin is a valuable tumor marker. PMID- 2581434 TI - Cisplatin, vinblastine, and bleomycin as second-trial therapy in ovarian carcinoma. A pilot study of the Gynecologic Oncology Group. AB - Ten patients with ovarian carcinoma whose tumors had progressed on first-trial chemotherapy were treated with cisplatin, vinblastine, and bleomycin (PVB) to determine the efficacy, dose range, and toxicity of this combination. Two dose levels of vinblastine were used. Objective responses occurred in 5/10 patients (3 CR, 2 PR), with a median response duration of 17.0 weeks. Toxicity was appreciable. One patient expired of bleomycin-induced pulmonary fibrosis. With the higher dose of vinblastine, four patients had grade III and three patients had grade IV hematologic toxicity. At the lower dose, two patients had grade II and one patient had grade III hematologic toxicity. PVB has activity in second trial therapy of ovarian carcinoma at the dose and schedule tested, but the role of this regimen in the future treatment of this disease remains to be determined. PMID- 2581435 TI - Future directions in the chemotherapy of head and neck cancer. PMID- 2581436 TI - Combination chemotherapy with high-dose methotrexate, bleomycin, and cisplatin in management of head and neck squamous cell carcinoma. AB - Fifty-nine patients with stage IV head and neck squamous cell cancer were treated with an intensive induction chemotherapy consisting of high-dose methotrexate leucovorin, bleomycin, and cisplatin. Forty-five patients had recurrent disease following surgery and/or radiation therapy. The response rate in this group was 22%, with a median response duration of 10 weeks and a median survival of 19 weeks. The median survival in responders was 20 weeks and in nonresponders 18 weeks. Fourteen previously untreated patients (13 T4 and one T2) received identical chemotherapy followed by radiation and/or surgery. The response to chemotherapy in previously untreated patients was impressively higher (93%). These patients had a median survival of 48 weeks, and 30% survived 2 years. The initial chemotherapy did not compromise the succeeding radiation therapy or surgery. Toxicities were frequent, but generally well tolerated. It is concluded that prior surgery and/or radiation therapy compromises the efficacy of subsequent chemotherapy in head and neck cancer. Responses to intensive chemotherapy prior to surgery and/or radiation therapy are excellent in patients with T4 tumors and provides a basis for further intensive treatment in attempts to augment cure rates. PMID- 2581437 TI - A phase II trial of cyclophosphamide and adriamycin in refractory squamous cell carcinoma of the head and neck. An effective salvage regimen. AB - A phase II trial of cyclophosphamide and adriamycin was carried out in 26 patients with recurrent squamous cell carcinoma of the head and neck, previously treated with cis-diamminedichloroplatinum-based regimens. The overall response rate was 46% (12/26 patients) with the median duration of response being 6.5 months. Cyclophosphamide and adriamycin is an active combination in patients with previously treated squamous cell carcinoma of the head and neck. PMID- 2581438 TI - Immunohistochemical analysis of progressively transformed follicular centers. AB - Using an in situ immunohistochemical technic and a panel of monoclonal antibodies directed to lymphocytes, dendritic reticulum cells, HLA-DR antigen and killer/natural killer cells, the cellular composition of progressively transformed follicular centers (PTFCs) was analyzed. PTFCs are large lymphoid aggregates, composed of BA1+B1+sIgM+sIgD+ small B-lymphocytes, admixed with randomly arranged OKT4+Leu-3a+ helper/inducer T-cells and Leu-7+ cells. Small islands of B1+BA1-sIgD- follicular center cells are present in the central part of PTFCs, but fail to form a true follicular center. DRC1+ dendritic reticulum cells are arranged abnormally, forming small, separate clusters or a loosely arranged network lacking the typical concentric pattern. Moreover, dendritic reticulum cells have less extensively developed cytoplasmic extensions and are devoid of surface-bound immunoglobulins. Based on these findings, it is suggested that blastic transformation of B-cells in PTFCs is incomplete. The occurrence of PTFCs among numerous well-formed, secondary lymphoid follicles, and their exclusive association with exaggerated follicle formation speaks against an intrinsic inability of dendritic reticulum cells to bind antigen-antibody complexes, but rather suggests that PTFCs represent early, transient stages in the transformation of primary into secondary lymphoid follicles. PMID- 2581439 TI - Enhanced detection of anti-tissue antibody by anti-immunoglobulin bound glucose oxidase. AB - An immunohistochemical procedure, using glucose oxidase (GO) linked to anti immunoglobulin serum, has been adapted to detect anti-tissue antibody to smooth muscle, parietal cells, and mitochondria. With this procedure antibody to smooth muscle was detected in a high percentage of normal sera. Anti-tissue antibodies were frequently detected in sera of patients clinically suspected of having an autoimmune disease when an immunofluorescence (IF) test to detect the antibodies was negative. The glucose oxidase immunohistochemical procedure to detect anti tissue antibodies is feasible and highly sensitive, and produces permanent results. The clinical usefulness of this procedure will have to be carefully evaluated. The detection of anti-tissue antibody in normal sera may indicate that such antibody is normally present in low concentration and that it may possibly have physiologic functions. PMID- 2581440 TI - Enzyme histochemistry in plastic-embedded sections of normal and diseased kidneys. AB - Interest in the role of mononuclear phagocytes in glomerulonephritis (GN) and in defining markers of renal neoplasms led the authors to study alpha-naphthyl acetate/butyrate esterase (ANAE/ANBE), alkaline phosphatase (AlkP), acid phosphatase (AcP), 5'-nucleotidase (5'N), and ATPase (ATP) activity in paraformaldehyde-fixed, plastic-embedded renal tissue from patients with a variety of pathologic conditions. These conditions included GN, renal tumors, and transplant rejection. Enzymatic staining for ANAE, ANBE, AcP, AlkP, and ATP was generally confined to tubules and collecting ducts in normal kidney. Nine of 10 cases of renal carcinoma had weakly to strongly positive reactions with AlkP, AcP, and ANAE; 9 of 10 cases of Wilms' tumor showed weakly positive reactions with AcP and ANAE, particularly in tubular structures. Severely damaged kidney allografts showed surprising retention of normal histochemical features. In all cases 5'N stained both glomerular capillaries and interstitial vasculature; ATPase and AlkP stained interstitial vessels only. Plastic embedding provides superb preservation of both microscopic anatomy and enzymatic activity, which may allow utilization of enzyme histochemistry for diagnostic and research purposes. PMID- 2581442 TI - A rapid method of staining ultrathin sections for surgical pathology TEM with the use of the microwave oven. AB - A rapid microwave method is described for staining ultrathin sections for surgical pathology transmission electron microscopy (TEM). Three sets of Epon sections of human heart biopsy were mounted on unsupported 200-mesh Rhodium coated copper grids and were stained with uranyl acetate (UA) and lead citrate. The first set of grids was stained for 15 seconds in each solution with the aid of a microwave oven, and the second set was stained routinely for 30 minutes in UA and 10 minutes in lead citrate at room temperature. The third control set was stained for 15 seconds in each solution without microwave bombardment. The overall image quality of the TEM micrographs generated by the "quick-stained" microwave enhanced sections was better than routine stained and control sections. The microwave-treated sections have more contrast, less artifacts in the form of precipitate, and a more uniform overall staining. PMID- 2581441 TI - A rapid immunostaining method utilizing preformed antibody-avidin-biotin peroxidase complexes. AB - A rapid immunostaining method utilizing a preformed antibody-avidin-biotin peroxidase complex that produces staining in paraffin sections and in frozen sections of tissues in 15 minutes is described. Although the complex did not produce staining with the common leukocyte monoclonal antibody, consistent staining was seen with most antibodies used. The complex gave consistent and reproducible staining for at least three months when maintained in storage at 4 degrees C. The results show that many available antibodies can be adapted to a rapid one-step staining procedure employing the avidin-biotin-peroxidase complex system. PMID- 2581443 TI - Pathology of small blood vessel disease in hypertension. AB - A pathogenic role for arterioles in hypertension has been postulated for many decades. Renal arteriolonecrosis, myointimal hyperplasia, and hyaline arteriolosclerosis are anatomic correlates of hypertension. The pathogenesis of these lesions is discussed as is contribution of these lesions to the perpetuation of hypertension. The importance of the extracellular matrix in the initiation and development of hyaline arteriolosclerosis is presented and correlated with the hemodynamic and pathophysiologic consequences of increased transmural pressure. The possibility of aiming therapy at arresting or ameliorating arteriolar disease is presented. PMID- 2581444 TI - The kidney in the pathogenesis of hypertension: the role of sodium. AB - In this review, we first summarize the evidence which indicates that the inability of the kidney to excrete salt and water normally, particularly when combined with increased salt intake, is frequently associated with hypertension. We then concentrate on the link between sodium and water retention and hypertension. The increase in blood pressure probably results from the increase in volume rather than from the increase in salt. Recent evidence suggests that an increase in volume in the lesser circulation stimulates the release of a sodium pump inhibitor, probably the putative natriuretic hormone, from the hypothalamus. This agent appears to affect cardiac and vascular smooth muscle by suppressing Na+,K+-ATPase, and hence Na+-K+ pump activity in both muscle cells and adrenergic nerve terminals. The sodium pump inhibitor is a heat stable small molecule but its chemical structure is still unknown. It is clearly different from atrial natriuretic factor. We conclude the review with speculations on the possible role of renotropin and various growth and growth inhibitory factors in the vascular structural changes. PMID- 2581445 TI - Genetic amniocentesis: a twelve years' experience. AB - The first 2,013 fetuses in 2,000 patients undergoing genetic amniocentesis at our institution were analyzed for the incidence of abnormal findings and for the safety and accuracy of the procedure. One percent of the patients were found to have aneuploid fetuses and another 1% were found to have elevated amniotic fluid concentrations of alpha-fetoprotein. Advanced maternal age was the indication for amniocentesis in 84% of the women with aneuploid fetuses. Thirty-two (1.6%) of the pregnancies ended in spontaneous abortion and 35 (1.7%) were terminated because of abnormal results of the prenatal diagnostic procedure. Our error rate was 0.15%, and tissue culture was successful in 97.7% of the procedures. During the latter part of our experience concurrent ultrasonography was utilized with the amniocentesis, resulting in a reduction in blood-tinged specimens from 15.0% to 5.2%. In experienced hands, midtrimester amniocentesis for the purpose of prenatal diagnosis of genetically determined defects is a safe, accurate, and valuable procedure for the identification of fetal abnormalities. PMID- 2581446 TI - Familial Sotos syndrome (cerebral gigantism): craniofacial and psychological characteristics. AB - Most reported cases of Sotos syndrome are sporadic, but autosomal dominant and recessive inheritance patterns have been suggested. Ascertainment of a two generation family through a 7-year-old proposita with a learning disability allowed the relatively unbiased study of two affected relatives. Developmental delay was not pronounced in the patient's mother or sister; craniofacial characteristics at variance with the characteristic description included acrocephaly and maxillary prominence. Steepness of the anterior cranial base angle and protrusion of the middle and lower face, shown in all three patients by cephalometric radiographs, deserve further evaluation as diagnostic criteria. PMID- 2581447 TI - Palliative exenteration--what, when, and why? AB - Between 1955 and 1981, 323 pelvic exenterations were performed at the Mayo Clinic. Fifty-nine (18%) were considered retrospectively to be palliative because of pelvic or aortic nodal metastasis, pelvic peritoneal involvement, pelvic wall involvement, bone involvement, or, in two cases, distant metastasis. The survivals were 47% at 2 years and 17% at 5 years. When metastatic nodal disease was found after irradiated pelvic recurrence, the 2- and 5-year survivals were 46% and 23%, respectively. Although exenteration procedures are designed to be curative, the palliative benefits obtained in this group of patients appear to be worthwhile and comparable to those achieved in advanced epithelial ovarian carcinoma for which aggressive surgical management is now strongly advocated. PMID- 2581448 TI - Plasma dextran levels after abdominal instillation of 32% dextran 70: evidence for prolonged intraperitoneal retention. AB - Postoperative ascites in patients receiving intraperitoneal dextran 70 may result from slow absorption. We tested this by instilling 250 ml of dextran 70 into the peritoneal cavity of patients undergoing tuboplasty. Serum dextran levels were undetectable until 24 hours after operation and rose during the next 4 days. Ascites in patients with intraperitoneal dextran 70 results from third spacing in response to the persistent osmotic load. PMID- 2581449 TI - Elevated maternal alpha-fetoprotein levels with subsequent fetal exsanguination. AB - Presented is a case with persistently elevated maternal serum alpha-fetoprotein and normal amniotic fluid alpha-fetoprotein values associated with subsequent fetal-maternal bleeding and fetal death. Fetal-maternal bleeding, with potential for rhesus sensitization and fetal death, should be considered in the presence of elevated serum alpha-fetoprotein levels. PMID- 2581450 TI - Interferon responses in maternal and fetal mice. AB - The kinetics of maternal-fetal interferon and a chemical interferon inducer were studied in Swiss-Webster white mice at 8, 15, and 19 days of gestation. Crude interferon was administered by maternal tail vein injection to one group. There was no transfer of interferon to the fetus despite high maternal levels. A chemical interferon inducer (10-carboxymethyl-9-acridanone) was given intramuscularly to a second group. Both maternal and fetal interferon responses rapidly reached significant levels, although the fetal response was less than that of the mother. Presence of the inducer was demonstrated in both maternal and fetal samples, indicating placental transport of the chemical to the fetus. The implications of these findings for the fetal immune response are discussed. PMID- 2581451 TI - Application of an ATNR rating scale to normal preschool children. AB - An Asymmetrical Tonic Neck Reflex Rating Scale was applied to data from 40 normal 3- and 5-year-old children. Raw scores representing degrees of elbow flexion in response to passive head rotation were converted using a four-point scale, and the results of eight trials in quadrupedal posture were summed. These results reinforce those of previous studies: the mean inhibition scores increased with age, whereas the variance decreased. Results also support further development of normative data for clinical use of the scale. PMID- 2581452 TI - The frequency of vestibular disorders in developmentally delayed preschoolers with otitis media. AB - This study investigated the frequency of vestibular disorders in developmentally disabled preschoolers who did and who did not have a history of otitis media. Fifteen children with a history of otitis media and fifteen children with no history of otitis media were given two tests for vestibular functioning: the Southern California Postrotary Nystagmus Test (SCPNT) and the Lateral Labyrinthine Righting Reaction (LLRR), acting on the head. The scores on these tests were dichotomized, and a correlation between these two tests as measures of vestibular function was obtained. Because this correlation did not reach a satisfactory level, two a satisfactory level, two separate chi-square analyses were performed to examine the frequency of vestibular disorders with otitis media. Both tests showed a statistically significant difference in the incidence of vestibular disorders between the two groups of children; the group having otitis media demonstrated more vestibular disorders. The SCPNT demonstrated more striking results than did LLRR. This finding is related to the two tests measuring different aspects of vestibular functioning; the separate chi-square analyses were performed to examine the frequency of vestibular disorders with otitis media. Both tests showed a statistically significant difference in the incidence of vestibular disorders between the two groups of children; the group having otitis media demonstrated more vestibular disorders. The SCPNT demonstrated more striking results than did LLRR. This finding is related to the two tests measuring different aspects of vestibular functioning; the SCPNT reflects semicircular canal functioning, and the LLRR reflects utricular and saccular functioning. The criteria used for LLRR (four seconds) also may have influenced the results obtained using this test. PMID- 2581453 TI - Cation and anion transport pathways in volume regulatory response of human lymphocytes to hyposmotic media. AB - The regulatory volume decrease of osmotically swollen human peripheral blood lymphocytes can be inhibited by agents acting on volume-activated K+- or Cl- transport pathways. Quinine, cetiedil, and 3,3'-dipropylthiadicarbocyanine were found to block the volume-induced K+ transport by interaction with sites on the outside face of the membrane, perhaps by competition with external K+. Drugs known to influence calmodulin action inhibit both volume-induced K+ and Cl- transport to varying degrees. Those inhibitors, particularly of K+ transport, are correlated with their calmodulin-antagonist activity. Penetrating sulfhydryl (SH) reagents (in contrast to nonpenetrating ones) are potent inhibitors of both volume-induced K+ and Cl- movements, indicating the presence of functionally important SH groups located within the membrane or at the cytoplasmic face. A number of agents, such as dipyridamole and oligomycin C, are specific inhibitors of the volume-activated anion pathway. In all respects studied, the inhibition characteristics of the volume-activated K+ pathway of lymphocytes resemble those of the Ca2+-activated K+ channel of red cells. In contrast, the volume-induced anion permeability differs from the primary anion-transport pathway of red cells. PMID- 2581454 TI - Intracellular Ca2+ levels and amylase secretion in Quin 2-loaded mouse pancreatic acini. AB - Dispersed mouse pancreatic acini were loaded with the Ca2+-sensitive fluorescence probe Quin 2. Stimulation with carbamylcholine or cholecystokinin-octapeptide (CCK-OP) resulted in a rapid increase in Quin 2 fluorescence, which returned to a lower and sustained plateau level within 2 min of secretagogue stimulation. The magnitude of the initial rise in fluorescence intensity and of amylase secretion were closely related to the concentration of agonist used. Maximal fluorescence changes and amylase secretion were noted with 1 X 10(-5) M carbamylcholine and 1 X 10(-9) M CCK-OP, whereas both responses were half maximal in the presence of 5 X 10(-7) M carbamylcholine and approximately 1 X 10(-10) M CCK-OP. The resting cytosolic free Ca2+ concentration, as measured by the intensity of Quin 2 fluorescence, was calculated to be 1.03 +/- 0.12 X 10(-7) M. Cytosolic free Ca2+ rose to 1.3 +/- 0.3 X 10(-6) M after addition of 1 X 10(-5) M carbamylcholine and 1.25 +/- 0.21 X 10(-6) M following 1 X 10(-9) M CCK-OP. Amylase secretion, but not the Quin 2 fluorescence response, was attenuated at higher secretagogue concentrations. Both secretagogue-induced Quin 2 fluorescence and amylase secretion were inhibited by secretagogue antagonists. Removal of Ca2+ from the extracellular medium resulted in a 48.8 +/- 2.0% reduction of carbamylcholine induced Quin 2 fluorescence. Following addition of carbamylcholine, CCK-OP was unable to stimulate a second increase in Quin 2 fluorescence without the intervening addition of a cholinergic antagonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581455 TI - Do hypoglycemic sulfonylureas inhibit Na+,K+-ATPase activity in pancreatic islets? AB - The view that the insulinotropic response to hypoglycemic sulfonylureas is somehow related to an inhibitory action of these drugs on either the Ca2+ activated K+ permeability or the Na+,K+-ATPase activity in pancreatic islet cells was investigated by measuring the effect of tolbutamide on 86Rb outflow and uptake, 45Ca outflow, and insulin release in rat pancreatic islets. Although tolbutamide inhibited 86Rb efflux from glucose-deprived islets, whether in the absence or presence of extracellular Ca2+ or ouabain, a primary action of the sulfonylurea on the Ca2+-responsive K+ channels appeared unlikely, because tolbutamide failed to suppress the increase in 86Rb outflow evoked by either the ionophore A23187 or ouabain. Glibenclamide also failed to suppress the increase in 86Rb outflow evoked by the ionophore. Moreover, tolbutamide itself stimulated quinine-sensitive 86Rb outflow from glucose-stimulated islets. Likewise, although tolbutamide inhibited an ouabain-resistant modality of 86Rb inflow into the islet cells, an inhibitory action of the sulfonylurea on the Na+,K+-ATPase appeared improbable, because tolbutamide failed to minimize and instead favored the cationic and secretory response to ouabain. It is concluded, therefore, that the capacity of tolbutamide to cause under suitable conditions continuous electrical activity in islet cells cannot be attributed to inhibition of either the Ca2+ sensitive K+ permeability or ouabain-sensitive Na+,K+-ATPase. PMID- 2581456 TI - Muscarinic inhibition of canine small intestinal motility in vivo. AB - The quiescent canine gastrointestinal tract responsed to close intraarterial acetylcholine with an atropine-sensitive, hexamethonium, and tetrodotoxin insensitive contraction, thus suggesting acetylcholine interacts with a muscarinic receptor located on the muscle. When the gut is actively contracting (spontaneously, in response to field stimulation or to motilin), acetylcholine caused a contraction followed by prolonged inhibition of contractions. No such inhibition was apparent after tetrodotoxin; therefore, the receptor for acetylcholine-induced inhibition was apparently on nerves. Neither the acetylcholine-induced excitation nor the inhibition was altered by hexamethonium or reserpine treatment. Both inhibitory and excitatory responses were greatly reduced by atropine, suggesting that both receptors were muscarinic in nature. McNeil A343 produced inhibition but no excitation. Tetrodotoxin, hexamethonium, reserpine, and pirenzepine all increased the concentration of McNeil A343 required for production of 50% inhibition, suggesting it acts via multiple mechanisms. Furthermore, pirenzepine reduced both the inhibitory and excitatory response to acetylcholine, suggesting that it is nonselective in its action on the neural inhibitory or muscular excitatory receptors. We suggest that the presynaptic muscarinic receptor responsible for inhibitory effects of acetylcholine is on the postganglionic cholinergic neuron itself and constitutes an important negative-feedback loop to reduce excessive cholinergic output. Although such a mechanism has been found in vitro previously, this is the first report in vivo in canine small intestine. PMID- 2581457 TI - Role of calcium in cholecystokinin-stimulated phosphoinositide breakdown in exocrine pancreas. AB - In dispersed acini from guinea pig pancreas cholecystokinin octapeptide (CCK-OP) stimulated breakdown of the phosphoinositides phosphatidylinositol (PI) and its phosphorylated derivative, phosphatidylinositol 4,5-bisphosphate (PI-P2), as measured by a decrease in the mass of PI and decreases in the content of [3H]PI and [32P]PI-P2 in acini prelabeled with myo-[2-3H]inositol or H3(32)PO4. The breakdown occurred in the absence of extracellular Ca2+ and when the CCK-OP induced rise in free intracellular Ca2+ ([Ca2+]i) was ablated by loading the acini with the Ca2+-selective indicator and chelator quin-2 in the absence of extracellular Ca2+. In contrast to CCK-OP, the calcium ionophore A23187 caused breakdown of PI and PI-P2 in the presence but not in the absence of extracellular Ca2+, although like CCK-OP A23187 stimulated 45Ca outflux, a measure of cellular Ca2+ mobilization, and amylase release during the first 5-10 min of incubation independent of extracellular Ca2+. In the absence of extracellular Ca2+ A23187 did not inhibit the ability of CCK-OP to cause PI breakdown. These results indicate that CCK-OP stimulates breakdown of PI and PI-P2 and that this breakdown is independent of extracellular Ca2+, mobilization of intracellular Ca2+, and the CCK-OP-induced rise in [Ca2+]i. These findings suggest that one of the initial events resulting from CCK-OP interaction with its receptor is phosphoinositide breakdown. PMID- 2581458 TI - Pregnancy-induced changes in sheep uterine and carotid arteries. AB - To characterize the effects of pregnancy on vascular tissue, intact segments of the uterine and carotid arteries were removed from nonpregnant and near-term pregnant sheep. Pressure-diameter relations were measured on isolated segments under activated (122 mM K+, 10(-4) M phenylephrine) and passive (0.1 mM Ca2+, 10( 5) M iodoacetic acid) conditions. DNA and RNA were determined spectrophotometrically. Collagen, elastin, and water contents were also measured. Pregnancy had no effect on either the mechanics or the biochemical properties of the carotid artery. However, there was a marked increase in internal radius in the uterine artery with pregnancy (0.060 +/- 0.016 vs. 0.198 +/- 0.019 cm). Active tangential stress increased, as did passive stiffness of the uterine artery. The collagen fraction decreased during pregnancy (57.2 +/- 2.4 vs. 45.7 +/- 2.2%), while elastin and RNA remained unchanged. A small decrease in DNA produced a significant increase in the RNA-to-DNA ratio. These data suggest that, in pregnancy, the uterine artery selectively undergoes a characteristic hypertrophy of its vascular smooth muscle. PMID- 2581459 TI - Permeability of blood-brain barrier to various sized molecules. AB - We studied disruption of the blood-brain barrier (BBB) by acute hypertension and a hyperosmolar solution. The goals were to determine whether 1) disruption of the BBB occurs primarily in arteries, capillaries, or veins, and 2) transport of different-sized molecules is homogeneous or size dependent. Sprague-Dawley rats were studied using intravital fluorescent microscopy of pial vessels and fluorescein-labeled dextrans (FITC-dextran, mol wt = 70,000, 20,000, and 4,000 daltons). The site of disruption was determined by the appearance of microvascular leaky sites. Transport of different-sized molecules was calculated from clearance of FITC-dextran. During gradual hypertension and osmotic disruption, all leaky sites were venular. Rapid hypertension produced venular leaky sites and, in some experiments, diffuse arteriolar extravasation of FITC dextran. Clearance of different-sized molecules was homogeneous during acute hypertension. In contrast, clearance of molecules during osmotic disruption was size dependent. The findings suggest that 1) venules and veins are the primary sites of disruption following acute hypertension and a hyperosmolar solution; 2) transport of different-sized molecules is homogeneous following acute hypertension, which suggests a vesicular mechanism; and 3) transport following hyperosmolar disruption is size dependent, which suggests that hyperosmolar disruption may involve formation of pores as well as vesicular transport. PMID- 2581460 TI - Adenosine inhibition of catecholamine-stimulated cardiac membrane adenylate cyclase. AB - Adenosine inhibition of hormone-sensitive adenylate cyclase activity was investigated using isolated myocardial membranes prepared from rat hearts. When cyclase activity was determined in membranes, using [alpha-32P]ATP as substrate, 10(-5) M adenosine inhibited isoproterenol-stimulated adenylate cyclase activity by 25% but did not inhibit basal activity or fluoride (5 mM) activation of the enzyme. The adenosine reduction of isoproterenol-sensitive cyclase activity was dependent on GTP but was not prevented by 10(-3) M theophylline. Adenosine neither appeared to compete with ATP for the substrate converting site of the enzyme nor reduced 5'-guanylyl imidodiphosphate activation of the enzyme. Inasmuch as lower concentrations of adenosine had no influence on enzyme activity, endogenous adenosine may be present in the adenylate cyclase assay. To obviate the effects of endogenous adenosine, the adenylate cyclase assay was then modified to a 2'-deoxy system with [alpha-32P]dATP used as the substrate in the presence of adenosine deaminase. With this assay system, the 15% inhibition of isoproterenol-stimulated adenylate cyclase activity produced by the adenosine receptor agonists, 10(-8) M 2-chloroadenosine or phenylisopropyladenosine, was prevented by 10(-4) M 8-phenyltheophylline or isobutylmethylxanthine (IBMX), respectively. While under these assay conditions, 10(-7) M 2',5' dideoxyadenosine, a P-site analogue, did not influence the hormone-sensitive cyclase activity. The 35% reduction of the hormone-sensitive enzyme produced by this analogue at 10(-5) M was not prevented by IBMX. These results suggest that nanomolar concentrations of adenosine analogues interact with a methylxanthine sensitive adenosine receptor that mediates the attention of membrane hormone sensitive adenylate cyclase activity. PMID- 2581461 TI - Injection of guanosine 5'-cyclic monophosphate into heart cells blocks calcium slow channels. AB - The role of guanosine 5'-cyclic monophosphate (cGMP) in the regulation of the ionic slow channels in heart muscle is less well known than that of adenosine 3,'5'-cyclic monophosphate (cAMP). The effects of intracellular injection of cAMP and cGMP in cultured chick embryonic heart (ventricular) cells by the liposome method were studied. Injection of cAMP into the cells induced spontaneous slow action potentials that could be blocked by verapamil and nifedipine. Injection of cGMP blocked on-going slow action potentials, and this effect was reversed by increasing cAMP. Thus both cAMP and cGMP are involved in the regulation of the slow calcium channels in myocardial cells, and the two cyclic nucleotides are antagonistic. PMID- 2581462 TI - Elastofibromatous lesion of the stomach in a patient with elastofibroma dorsi. AB - A 69-year-old woman underwent partial gastrectomy because of peptic ulcer which resisted medical treatment. The resected stomach exhibited a wide thickening of the antral wall around a 1.2 X 0.8 cm ulcer. The cut surface showed a gray-white thickened submucosal layer and had a rubbery elastic consistency. Microscopically, the thickened areas consisted of abundant acellular collagen fibers containing numerous elastinophilic, thick, serrated fibers and globules, identical with the elastofibroma fibers seen in elastofibroma dorsi. Reexamination of the patient revealed bilateral subscapular masses; one of these was biopsied and proved to be an elastofibroma dorsi. PMID- 2581464 TI - A mononuclear cell-derived histamine releasing factor in asthmatic patients. II. Activity in vivo. AB - In an attempt to study the role of lymphokines in asthma, lymphocytes from asthmatic patients were stimulated in vitro with skin test-positive allergen (dust mite) or with non-specific mitogen-phytohaemagglutinin for 4 h, then washed carefully and cultured alone for 16 h. Cell-free supernatants were subsequently collected and applied in the basophil histamine release test in vitro and in bronchial provocation test and skin prick test in vivo. Supernatant of non stimulated lymphocytes from asthmatic patients released significant amounts of histamine from basophils. Stimulation of lymphocytes with specific allergen or phytohaemagglutinin augmented the supernatant-induced histamine release. Lymphocyte supernatants from the majority of patients also induced bronchoconstriction and elicited skin wheal and flare reaction in vivo. PMID- 2581463 TI - Inhibitory effect of cyclosporin A on histamine release from human leukocytes and rat mast cells. AB - The influence of cyclosporin A (CyA) on human basophil histamine release induced in vitro by specific antigen, anti-IgE, calcium ionophore A23187, or concanavalin A (Con A) was studied. CyA inhibited the release induced by these four stimulators. It is suggested that the drug acts directly on the target cell, since similar effect was obtained with isolated peritoneal rat mast cells. The basophil histamine release was not changed by a non-immunosuppressive cyclosporin derivate. PMID- 2581465 TI - Inhibitory effect of N-(3', 4'-dimethoxycinnamoyl) anthranilic acid (N-5') on SRS A mediated bronchoconstriction in the guinea pig in vivo. AB - Slow-reacting substance of anaphylaxis (SRS-A) is an important factor mediating bronchoconstriction in asthma. We developed a guinea pig model for SRS-A-mediated bronchoconstriction induced by antigen inhalation. Using this model, we investigated the effect of N-(3', 4'-dimethoxycinnamoyl) anthranilic acid (N-5'), a new anti-allergic drug, on the bronchoconstriction. FPL 55712 inhibited most of the bronchoconstriction induced by antigen inhalation. N-5' inhibited the antigen induced bronchoconstriction in a dose-dependent fashion. Intraperitoneal administration of 200 mg/kg N-5' was effective for 40 min after antigen inhalation, while the effect of 60 mg/kg lasted only 7 min. On the other hand, 200 mg/kg N-5' showed no inhibitory effect on the bronchoconstriction caused by direct inhalation of leukotriene C4, a component of SRS-A. These findings indicate that one of the anti-allergic actions of N-5' is due to inhibition of synthesis and/or release of SRS-A. PMID- 2581466 TI - Release of histamine from human leukocytes by one preparation of IgG oligomers. AB - In preliminary experiments aimed at investigating the effect of covalently cross linked human myeloma subclass proteins on histamine release from human leukocytes, we observed one preparation (designated here IgG-HR) made from pooled, purified immunoglobulin G, which consistently released histamine from these cells. Dimers and trimers, but not monomers isolated from columns of Sephadex G-200 and Ultrogel AcA22 following incubation of immunoglobulin G (Nordic Laboratories) with dimethyl suberimidate, released histamine from cells of all donors tested. In contrast, cells from the same donors showed variable responsiveness to dimers of IgE (prepared by similar techniques) or to anti-IgE. IgG-HR failed to release histamine from a "basophil-rich" mononuclear cell preparation depleted of most of the erythrocytes, platelets, neutrophils and eosinophils by centrifugation through a Ficoll-Hypaque cushion. The data suggest that IgG-HR was releasing histamine indirectly from basophils by first interacting with another cell. IgG oligomers prepared from different sources of pooled, purified IgG failed to release histamine. Although we did not have sufficient IgG-HR to adequately define this releasing activity, we feel that the data represent a potentially novel, if rare, mechanism of mediator release involving basophils and another cell. PMID- 2581467 TI - Effects of long-term treatment with low dose cimetidine on allergen-induced airway responses and selected immunological parameters in atopic asthmatics. AB - Twenty asymptomatic atopic asthmatics were treated with either cimetidine 100 mg orally (13 patients) or placebo (7 patients) once a day for 4 weeks. Bronchial challenges were performed with the pertinent allergen immediately before and 2 and 4 weeks after the initiation of treatment and, finally, 4 weeks after the cessation of treatment. Before each challenge blood was drawn for the determination of specific IgE antibody levels (RAST procedure) and total IgE (PRIST), allergen- and anti-IgE-induced basophil histamine release, and mitogen induced lymphocyte (3H)-thymidine incorporation. Patients treated with cimetidine were found to be significantly (P less than 0.05) less responsive to bronchial allergen challenge during the treatment than before it; patients treated with placebo were more reactive (P less than 0.05) 14 days after the initiation of treatment. The difference in responsiveness to treatment between the placebo and the cimetidine groups was significant 14 days (P less than 0.01) and 4 weeks (P less than 0.05) after the initiation of treatment; no significant difference in allergen responsiveness was recorded between the groups 1 month after cessation of treatment. No clear-cut changes in specific IgE antibody or total IgE levels, histamine release capacity, or mitogen-induced lymphocyte responsiveness were observed in either group, except that lymphocytes from cimetidine-treated patients tended to show an increased ratio of PHA- to PMA-induced thymidine incorporation. Thus, it was found that the treatment of asymptomatic atopic asthmatics with low-dose cimetidine reduced their allergen sensitivity in bronchial provocation tests by a mechanism which remains to be elucidated. PMID- 2581468 TI - Sensitive glass microfibre-based histamine analysis for allergy testing in washed blood cells. Results compared with conventional leukocyte histamine release assay. AB - The new microfibre method for allergy testing is based on basophil histamine release after challenge with suspected allergens in samples of 50 microliter washed blood cells. Released histamine is bound to microfibres and measured after removal of interfering substances by washing. The microfibre method was compared with the conventional leukocyte histamine release assay in 18 allergic patients tested with 10 different allergens. It was found that the same individuals responded with histamine release to the same allergens in both assays, and the number of responders was almost identical. Also the dose-response curves and the cell sensitivity were almost identical, which further substantiated identity between the results obtained by the new microfibre method and the conventional assay. A comparison between the microfibre method and in vivo provocation tests showed good agreement when comparing the number of positive and negative responses in these test. The new method overcomes the problems in allergy testing, where only small amounts of blood are available and many tests have to be carried out. PMID- 2581469 TI - The prolongation of local anaesthetic action with dextran. The effect of molecular weight. AB - Field blocks of the inguinal region were performed in two groups of patients, in one group using a mixture of 0.5% bupivacaine, 1:200 000 adrenaline and dextran 110 and in the second group using a mixture of 0.5% bupivacaine, 1:200 000 adrenaline and dextran 150; the study being performed in a double-blind fashion. The dextran 150 mixture produced a highly significant increase (p less than 0.01) in the duration of the block when compared with the dextran 110 mixture. The authors conclude that the use of dextran of increasing molecular weight increases the duration of action of local anaesthetics correspondingly. PMID- 2581470 TI - Radioimmunoassay of cyclic AMP can provide a highly sensitive assay for adenylate cyclase, even at very high ATP concentrations. AB - Modifications of the cyclic AMP radioimmunoassay of Cailla et al. [in Hormones and Cell Regulation (J. Dumont and J. Nunez, eds.), Vol. 4, pp. 1-24, Elsevier/North-Holland, Amsterdam/New York (1980)] allowed its use in the determination of adenylate cyclase activity, which was otherwise precluded by high blank values. These high values originate mainly from chemically formed cyclic AMP and from ATP cross-reactivity. The simultaneous presence of ATP and magnesium ions generates cyclic AMP under the alkaline conditions used to succinylate the sample; this interference can be dealt with either by chelation of Mg2+ ions with EDTA during succinylation or by periodic acid oxidation of samples prior to succinylation. In addition, ATP itself contributes to blank values by its cross-reactivity, especially when working with high concentrations of this substrate. This interference can be decreased by a batch adsorption of ATP or oxidized ATP on alumina. Detailed procedures were discussed, with the choice of the additional steps to the standard method of Cailla et al. having to be made on the basis of the sensitivity requirements. When preventing ATP cyclization, the radioimmunoassay was as sensitive as methods using [alpha 32P]ATP as substrate. Elimination of ATP can improve the sensitivity by one order of magnitude. This method is especially interesting with high ATP concentrations and/or with low cyclic AMP production. PMID- 2581472 TI - Silver staining for selective detection of histones in polyacrylamide gels. AB - A simple silver-staining technique was developed for selective visualization of histones in polyacrylamide gels. The specificity of the stain was confirmed using a variety of protein mixtures and isolated histones. The staining procedure requires a relatively short time to perform (2.5-3 h), and the sensitivity to lysine-rich histones is comparable to that of the conventional Coomassie blue stain (about 0.1 microgram per band). A possible mechanism for the selective staining was deduced from a comparison with the widely used ultrasensitive silver staining. PMID- 2581471 TI - An assay to determine the kinetics of RNA cleavage. AB - To evaluate some synthetic catalysts that mimic ribonuclease, a quantitative assay has been developed that measures the number of phosphate diester bonds cleaved in a polymeric RNA substrate. This assay involves determining the number of 5'-oligonucleotide termini produced during the cleavage, using polyuridylic acid as the substrate. Samples withdrawn from the kinetic run are treated with venom exonuclease (phosphodiesterase I), and the increase in the concentration of uridine is determined by high-performance liquid chromatography. A related assay has been developed to monitor the catalyzed cleavage of the dinucleotide uridylyl(3'----5') uridine (UpU). PMID- 2581473 TI - Resolution of the isoenzymes of soybean lipoxygenase using isoelectric focusing and chromatofocusing. AB - Isoelectric focusing in thin-layer polyacrylamide gels has been applied to the analysis of the enzymes involved in the formation and destruction of peroxides in soybeans [Glycine max (L.)], lipoxygenases and peroxidases, respectively. As a result of differences in pH optima for catalytic activity, lipoxygenases were selectively detected by adjusting the pH employed for activity-specific staining. Type-1 lipoxygenase was revealed not only by staining based on the conversion of linoleic acid to hydroperoxide but also by two stains based on the reduction of the hydroperoxide. These methods were found to be suitable for the analysis and characterization of isoenzyme patterns in different soybean cultivars. A substantial difference in the distribution of lipoxygenases maximally active near pH 7 was observed for cultivars Provar and Vickery. A similar degree of separation of the isoenzymes was achieved on a larger scale using chromato focusing in the pH range 7.4-5.0. PMID- 2581474 TI - Blot analyses of glycoconjugates: enzyme-hydrazide--a novel reagent for the detection of aldehydes. AB - A procedure for the general staining of glycoproteins and other glycoconjugates on protein blots has been developed. Aldehydes are formed on the sugars of glycoconjugates by periodate oxidation which then react with hydrazide groups of enzyme-hydrazides, a novel reagent designed for aldehyde detection. The bound enzyme-hydrazide is demonstrated histochemically. The new assay is advantageous over periodic-acid Schiff staining of gels as its reagents and signals are stable and the process is simple and expedient, and provides greater sensitivity. PMID- 2581475 TI - Selective isolation of mercurated DNA by affinity chromatography on thiol matrices. AB - A method for isolating picomole quantities of nascent mercurated DNA from a mixture of cellular nucleic acids using affinity chromatography on thiol-agarose is described. Analysis of mercurated DNA (HgDNA) isolated in the presence of in vivo-labeled cellular RNA or in vitro-synthesized RNA showed a low level of RNA contamination, about 0.04-0.16%, in the HgDNA. Comparative binding studies on different thiol matrices showed that the efficiency of binding of HgDNA was related to the nature but not to the SH content of the matrix used. Another important parameter for binding was the structure of HgDNA. The recovery was 98% with large nascent HgDNA sedimenting at about 30 S, whereas for short pulse labeled single-stranded HgDNA (20-50 nucleotides long), the maximum recovery was 60%. The effect of the structure of HgDNA on the binding to the thiol matrix was probed using a variety of well-defined mercurated structures obtained from phage DNA and their restriction fragments. For DNA containing one 5-mercuricytidine 5' triphosphate (HgdCMP) residue at each 3'-end, short fragments (size range, 230 510 bp) were bound quantitatively. With larger fragments (size range, 490-1100 bp), the binding decreased progressively with increasing size. DNA fragments larger than 1060 bp did not bind to the matrix. Single-stranded DNA containing only one HgdCMP at one end did not bind to the matrix even in the size range 200 1100 nucleotides. In contrast, continuous stretches of HgdCMP residues in one strand or short stretches of HgdCMP residues at random in both strands permit quantitative binding irrespective of size. PMID- 2581476 TI - Electrospray interface for liquid chromatographs and mass spectrometers. PMID- 2581478 TI - Ultrastructural observations on nucleolar changes during mouse spermiogenesis. AB - When applying a new silver staining technique on developing mouse spermatids, it could be shown that strong argyrophilia in the "padlock" like nucleolus of very early spermatids is confined to its fibrillar and granular component, whereas the fibrillar centre is devoid of silver. During further steps the granular component disappears together with the fibrillar centre. The last remaining nucleolar part, the silver positive fibrillar component disintegrates at the beginning of nuclear elongation. Instead of it clusters of coiled fibers bordered with granules of approximately 40-60 nm in diameter, both silver positive, appear in the nucleoplasm. As chromatin condensation proceeds, these silver positive structures, now intimately attached to the centrally occurring focus of condensing chromatin decrease more and more in size and density. In later stages accumulations of silver positive material will appear in the posterior region of the nucleus, will leave it, and stays as silver positive "juxtanuclear body" in the nuclear pocket formed by the redundant nuclear envelope. As spermatid development continues, the "juxtanuclear body" disappears together with the nuclear pocket. The small silver positive fibrous clusters disintegrate too so that the mature sperm only contains the space in which they formerly existed, now called "nuclear vacuole". A possible connection between silver staining pattern and RNA synthesis is discussed. PMID- 2581477 TI - Sex differences in circadian rhythms of several variables in lymphoreticular organs, liver, kidney, and corneal epithelium in adult CD2F1 mice. AB - In this paper data resulting from an investigation into the influence of sex on selected circadian rhythms in lymphoreticular organs, liver, kidney, and corneal epithelium of adult CD2F1 mice are reported. Increased organ weight, total DNA and RNA in the spleen, total DNA and [3H thymidine [( 3H]TdR) incorporation into DNA in the thymus, and [3H]TdR incorporation into DNA in the liver and bone marrow in female mice compared to male littermates is demonstrated. In contrast, kidney weight and [3H]TdR incorporation into DNA as well as the corneal epithelium mitotic index are greater in male mice. Except for the corneal epithelium mitotic index and total splenic RNA and DNA, circadian rhythmicity in the variables studied is validated using the cosinor method of rhythmometric analysis in male but not in female mice. The lack of sinusoidal rhythmicity in female mice is presumed to be due to asynchrony of estrous cycling between mice within this group. Moreover, a differential organ response to exogenous testosterone enthanate is reported. The administration of this hormone suppresses [3H]TdR incorporation into DNA in the thymus and liver but not in the spleen or bone marrow at 18, 42, or 72 hr after injection. PMID- 2581479 TI - Effects of trimethaphan on arterial blood histamine and systemic hemodynamics in humans. AB - Because of lack of direct evidence of histamine release by trimethaphan, the authors determined serum histamine levels and hemodynamic responses to trimethaphan administration in 19 consecutive patients. Group 1 patients (n = 7) received a single intravenous injection of trimethaphan, 0.5 mg X kg-1, while awake and again during stable halothane-nitrous oxide anesthesia. Group 2 patients (n = 6) were pretreated with intravenous H1 (chlorpheniramine, 0.1 mg X kg-1) and H2 (cimetidine, 4 mg X kg-1) receptor antagonists administered 15 min before trimethaphan, 0.5 mg X kg-1, in the awake and anesthetized states. In Group 3 (n = 6), the effects of infusion of trimethaphan, 3 mg X min-1 for 15 min, were studied during halothane-nitrous oxide anesthesia. In Group 1, bolus doses of trimethaphan were associated with maximal increases in serum histamine from 0.56 +/- 0.14 to 2.56 +/- 0.35 ng X ml-1 (P less than 0.01) and from 0.60 +/ 0.11 to 2.58 +/- 0.33 ng X ml-1 (P less than 0.01) 2 min after drug administration in the awake and anesthetized states, respectively; there were also clinical manifestations of histamine release. Mean arterial pressure decreased maximally after 5 min in the awake (from 92.0 +/- 3.4 to 69.9 +/- 2.2 mmHg; P less than 0.01) and anesthetized (from 82.6 +/- 3.7 to 57.3 +/- 2.5 mmHg; P less than 0.01) states, and was associated with increases in cardiac output and heart rate; stroke volume increased in the awake state only.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581480 TI - Atracurium: hypotension, tachycardia and bronchospasm. PMID- 2581481 TI - Cross-reactivity among Chenopodiaceae and Amaranthaceae. AB - Pollen extracts from Atriplex latifolia, Beta vulgaris, Salsola kali and Amaranthus retroflexus were compared with an extract from Chenopodium album by both in vivo and in vitro methods. Skin prick tests on 20 C. album-sensitive patients were positive with all extracts. RAST inhibition together with two dimensional immunoelectrophoresis and two-dimensional radioimmunoelectrophoresis indicate that common allergenic determinants are present. Electrophoretic transfer for detection of IgE binding molecules from sodium dodecyl sulfate polyacrylamide gel electrophoresis or isoelectricfocusing gels suggests that the common allergenic determinants are present in molecules with various molecular weights or isoelectric points. PMID- 2581482 TI - Preliminary report on histamine release, circulating immune complexes, and complement activation in children with atopic dermatitis after oral challenge with milk and egg antigens. AB - The effects of dietary restriction and food challenge were evaluated in five children with atopic dermatitis, as a possible predictive marker for the dietary management of this clinically perplexing disease. Two of the five showed significant elevation of plasma histamine; an additional two demonstrated the presence of immune complexes and in the fifth no change was described. The results of these study lend further support to the causal relationship between food allergy and atopic dermatitis, and suggest that the use of these immunologic parameters may be useful in the clinical assessment and management of these patients. PMID- 2581483 TI - Diversity of African swine fever virus. AB - An African swine fever virus is an heterogeneous population, consisting of clones having different biological characteristics in respect to hemadsorption, virulence, infectivity, plaque size, and antigenic determinants. The following observations were made: Nonhemadsorbing virus (NHV) have been segregated from field isolates from Haiti (HT-1) and a bone marrow- and buffy coat-passaged Portuguese isolate (L'60BM89BC1) and appear as a major, minor, or equal mixture with hemadsorbing viruses in the virus population. Biological characteristics of the virus inoculated into pigs often differed from viruses isolated later from the same pigs. Virulence and nonhemadsorbing characteristics of isolated clones were genetically stable. The lethal effect of 2 NHV clones of L'60BM89BC1 virus was dose-dependent; small doses of virus induced immunologic deaths or recoveries from the clinical disease in pigs, and large doses induced acute deaths. The NHV of Lisbon isolate of 1960 (L'60) and HT-1 isolate share the same antigenic determinants for inducing protection. Tengani isolate contained clones of distinctly different antigenic determinants, not shared by L'60 or HT-1 isolate that enabled it to overcome the protection induced by the other clones. Passaging of an African swine fever virus isolate in pigs or cell cultures may readily alter the proportions of the different clones in the population and thereby change its overall characteristics. A new virus population with atypical hemadsorption was found in HT-1 field isolate and L'60BM89BC1 virus. PMID- 2581484 TI - Cell-mediated and humoral immune response to Mycoplasma hyopneumoniae in pigs enhanced by dextran sulfate. AB - The effect of dextran sulfate (DS), known to be cytotoxic to macrophages, on the cell-mediated and humoral immune response to nonviable Mycoplasma hyopneumoniae in pigs was investigated. The cell-mediated immune response was determined by means of lymphocyte transformation a test, using uptake of [3H]thymidine in a microculture system and the humoral immune response by means of a microplate complement-fixation test. Peripheral blood lymphocytes from pigs vaccinated with nonviable M hyopneumoniae and DS incorporated substantially more [3H]thymidine than did those from pigs given Mycoplasma or DS alone. The transformation of lymphocytes from M hyopneumoniae-DS vaccinated pigs was enhanced when M hyopneumoniae cells used in the assay system were heated at 60 C for 30 minutes. Similarly prepared M flocculare and M hyorhinis cells also stimulated lymphocytes from M hyopneumoniae-DS vaccinated pigs, but not nearly as great as when M hyopneumoniae cells were used. The humoral antibody response and the cell mediated immune response to nonviable M hyopneumoniae was markedly enhanced by DS. Pigs were vaccinated with nonviable M hyopneumoniae and/or DS 4 times and challenge exposed intratracheally with viable M hyopneumoniae. Pigs vaccinated with M hyopneumoniae and DS had less severe pneumonia than did nonvaccinated pigs. PMID- 2581485 TI - Serum pancreatic polypeptide and amylase concentrations in dogs with experimentally induced acute pancreatitis. AB - Serum concentrations of immunoreactive pancreatic polypeptide (IPP) were measured serially for 7 days after experimental induction of acute hemorrhagic pancreatitis in dogs by infusion of oleic acid into the pancreatic duct. The mean serum IPP concentrations in dogs with pancreatitis were increased significantly (P = 0.013) for 96 hours after induction of pancreatitis. Providing food at 108 hours resulted in significant increases (P = 0.032) in mean serum IPP concentrations in sham-operated control dogs compared with dogs with induced pancreatitis. This was attributed to cephalic-phase release of IPP due to a conditioned response that resulted from feeding immediately after each blood sampling. Mean serum IPP concentrations returned to base line more quickly than did mean serum amylase concentrations in dogs with pancreatitis. PMID- 2581486 TI - Oral papillomatosis in New Zealand white rabbits. AB - Oral papillomas were seen in 31% of New Zealand white rabbits (n = 51) examined from 2 local sources. Papillomavirus structural antigens were detected by the peroxidase-antiperoxidase technique in cells of the stratum spinosum which contained basophilic intranuclear inclusions. Homogenates of papillomas hemagglutinated mouse RBC and also induced papillomas on the ventral surface of tongues, but not bulbar conjunctiva or vulva, os susceptible rabbits. The same oral papilloma homogenate induced fibromas in neonatal hamsters. Homogenates of hamster fibromas did not cause lesions on tongues of susceptible rabbits. PMID- 2581487 TI - Fascial compartments of the equine crus. AB - The deep fascia of the equine crus was dissected grossly and separated into 2 layers, the superficial and deep laminae of the deep fascia. Attachments of these fascial laminae to the tibia and fibula formed 5 separate osteofascial compartments: cranial, lateral, caudal deep, caudal intermediate, and caudal superficial. Cranial tibial vessels and the deep peroneal nerve entered the cranial compartment through separate fascial hiatuses; this may predispose the equine crus to the occurrence of compartmental syndromes with clinically recognizable neural deficits. PMID- 2581489 TI - The effect of deferoxamine on bleomycin-induced lung fibrosis in the hamster. AB - Bleomycin is a commonly used antineoplastic compound that can produce a dose- and time-dependent pneumonitis and fibrosis in humans. The mechanism of bleomycin induced fibrosis is not known. However, current data suggest that the production of oxygen radicals by way of a ferrous ion-molecular oxygen mechanism might be related to the pulmonary fibrosis. Therefore, we evaluated the possibility that parenterally administered deferoxamine, an iron chelating compound, could modulate the morphologic and biochemical estimates of bleomycin-induced lung fibrosis in hamsters. Deferoxamine pretreatment and daily injection for 21 days after intratracheally administered bleomycin resulted in a 33% reduction in lung collagen accumulation compared with that after bleomycin treatment alone. However, fibrosis was still present in the bleomycin-deferoxamine group; the animals showed a 142 and 150% increase in lung collagen compared with that in saline- and deferoxamine-treated control animals, respectively. Morphologic estimates of the severity of fibrosis in the bleomycin-deferoxamine treatment group were reduced when compared with the bleomycin treatment group alone, but was increased compared with saline- and saline-deferoxamine-treated control animals. These data indicate that deferoxamine treatment reduces the severity of bleomycin-induced pulmonary fibrosis in hamsters. The mechanism might be by the prevention of iron-catalyzed, free-radical formation. PMID- 2581488 TI - Serum amylase and isoamylases and their origins in healthy dogs and dogs with experimentally induced acute pancreatitis. AB - Agarose-gel electrophoresis was used to study isoamylases in tissues and sera of healthy dogs and the sera of dogs with experimentally induced acute pancreatitis. Three or 4 isoamylases were found in the serum of healthy dogs; they were numbered 1 to 4 with respect to their degree of anodal migration. Peak 4 isoamylase, the slowest migrating (most cathodal), was the major isoamylase fraction in sera and tissues of healthy dogs. Peak 3 was identified as a pancreas specific isoamylase. Absolute total serum amylase and total isoamylase concentrations increased significantly in dogs with pancreatitis compared with values for control dogs (sham-operated). The relative increase in peak 3 isoamylase was greater than that seen with total amylase or the other isoamylases. The decrease in total serum amylase and isoamylase concentrations paralleled each other; however, peak 3 remained proportionally high longer than did total amylase and the other isoamylase fractions. These findings indicate that measurement of peak 3 isoamylase concentrations may be of diagnostic value in dogs with suspected pancreatitis with normoamylasemia and in dogs with extrapancreatic hyperamylasemia. PMID- 2581490 TI - The poor man's isoamylase analysis (wheat inhibitor). Does it work? AB - The value of a wheat inhibitor assay to measure the pancreatic isoamylase fraction in the serum was evaluated in a clinical trial. Fifty-four patients with a variety of disorders and wide range in serum amylase levels were studied comparing pancreatic isoamylase levels measured by both cellulose acetate membrane electrophoresis and wheat inhibitor assay. The overall correlation was excellent (r = 0.96), and was best when the total serum amylase was high. The predominate serum isoamylase was correctly predicted in 45 of 54 (83%) patients, with an overall specificity of 73 per cent and sensitivity of 96 per cent. Because it is easy to perform, the test is recommended for clinical use by those without access to more sophisticated forms of isoamylase analysis. PMID- 2581491 TI - Carcinoid carcinomatous meningitis. AB - A 67-year-old woman with metastatic carcinoid tumor developed neurologic signs and symptoms of left facial paralysis and progressive lower extremity weakness. Results of cytologic evaluation of cerebrospinal fluid were normal. However, biochemical analysis of the cerebrospinal fluid showed extreme elevations of 5 hydroxyindoleacetic acid and serotonin, consistent with carcinomatous meningitis caused by carcinoid tumor. Subsequent contrast myelography confirmed the presence of meningeal metastases. PMID- 2581492 TI - The nursing home resident with dementia. Clinical care, ethics, and policy implications. AB - How much treatment should be given elderly patients with dementing illness is controversial. Nursing home care should be based on palliation, rehabilitation, and the control of coexisting illness. Ethical standards are advanced from the principle that the life and well-being of the demented nursing home resident should be protected. The decision to forego medical treatment is justified only when the life of an affected person is burdened by severe, unrelieved suffering or by the absence of self-awareness and relational potential. Introducing this philosophy of care to institutions requires a greater societal commitment to nursing home care. PMID- 2581494 TI - Nb rat prostate adenocarcinoma model: metastasis. AB - The Nb rat prostate adenocarcinomas - androgen insensitive II and III - were utilized in three experiments utilizing protamine sulfate, persantine (dipyridamole), and heparin-cortisone combination as agents evaluated for their ability to affect the incidence of systemic metastasis in this animal model. The results indicate that all agents tested were effective in reducing metastasis; protamine and persantine (10 mg/kg/day) being the most effective with 0% metastasis. In addition, animals treated with protamine had a statistically significant decrease in tumor volume. The mechanism responsible for this decrease remains unclear at present. PMID- 2581493 TI - Preleukemic myelodysplastic syndromes (MDS): pathogenetical considerations based on retrospective clinicomorphological sequential studies. AB - Analysis of myelodysplastic syndromes (MDS) in 77 patients terminating in "overt" leukemia revealed sequential changes of marrow morphology with respect to cellularity and involvement of lineages, indicating that different "forms" of MDS represent in reality different phases. Three main phases were observed, which occurred in the following non-reversible sequence: (a) hypocellular dysplasia (H), (b) hypercellular dysplasia with predominance of erythropoiesis (E), and (c) with predominance of myelo(mono)poiesis (MM). Published studies suggest that these phases represent different manifestation stages of the stem cell lesion leading to MDS. Manifestation may probably be promoted by factors causing marrow aplasia. Transition to "overt" leukemia in several cases occurred locally, not throughout the whole marrow. In some patients a mature myelo(mono)-cytic cell population showed the capacity for widespread tissue infiltration, characteristic of leukemic cells. This argues against the theory that "overt" leukemia is the result of continuous dedifferentiation in MDS, but favours the concept of multiple initiating "events" leading to evolution of a leukemic subclone within a myelodysplastic clone. A connection between leukemia differentiation and MDS phase, from which leukemia developed, was also observed indicating that the risk of different stem cell subpopulations to become the target of the leukemia initiating "event" varies during the course of myelodysplasia. PMID- 2581495 TI - Multiple transcriptional activation of cellular oncogenes in human head and neck solid tumours. AB - Expression of six cellular oncogenes in fresh human tumours and normal tissue from head and neck regions of 20 patients were assessed: 7 samples of normal tissue (controls), 4 premalignant (pleomorphic salivary adenoma) and 14 malignant tumours (squamous cell carcinoma) were examined. Normal and malignant tissue was available from the same patient in four cases, whereas normal and premalignant tissue in one case. Significant elevation of Ha-ras, Ki-ras, and myc oncogene expression were found both in premalignant and malignant tumours as compared to the normal tissue. Oncogenes fes, abl, and sis were expressed at similar low levels in all tissues examined. The results suggest activation of multiple oncogenes in premalignant and malignant tumours from the human head and neck regions. PMID- 2581496 TI - Polyneuropathy and IgM monoclonal gammopathy: studies on the pathogenetic role of anti-myelin-associated glycoprotein antibody. AB - Attention has recently been directed toward patients having a polyneuropathy and a monoclonal IgM anti-myelin-associated glycoprotein (anti-MAG) antibody. The possibility of a pathogenetic role for the anti-MAG antibody in the evolution of the polyneuropathy and in the development of central nervous system signs, including tremor and ataxia, remains unresolved. In 5 patients with this syndrome whose clinical courses were followed closely, in 1 of whom a complete postmortem examination of the nervous system was performed, we made the following observations: the anti-MAG antibody did not localize to the compact layer of the myelin sheath in affected nerves, but did localize to areas of myelin splitting; anti-MAG antibody present in the sural nerve of an affected individual for 7 years was not associated with progressive pathology; anti-MAG antibody was not deposited in the central nervous system of an affected individual, although the antibody did bind to these same tissues in vitro; deposition of anti-MAG antibody observed at postmortem examination did not correlate with the degree of pathological change; and study of the peripheral nervous system favored a primary axonal neuropathy with secondary demyelination. PMID- 2581497 TI - Prenatal diagnosis by amniocentesis. AB - One of the major applications of somatic cell genetics to clinical medicine is in the area of prenatal diagnosis by genetic amniocentesis, which permits the accurate prediction of fetal disease and allows pregnant women to selectively maintain unaffected fetuses. The more recent developments in recombinant DNA research promise to expand tremendously the potential of this technique. PMID- 2581498 TI - Beta-adrenergic blocking drugs. AB - There are currently six beta-adrenoceptor blocking drugs on the market. Although all the drugs competitively interact with the beta-adrenergic receptors, their pharmacokinetics and ancillary properties distinguish them from one another. By understanding these differences, the various beta-adrenoceptor drugs can be rationally used to a therapeutic advantage. PMID- 2581499 TI - The electrophysiology of acute myocardial ischemia. AB - The cellular events leading to clinical manifestations of acute (less than 30 minutes) ischemia are discussed, with emphasis on the role of early extracellular K+ accumulation and its effect on sodium current kinetics, which causes changes in excitability, conduction, and refractory periods. These are the cellular phenomena responsible for ST elevation, reentry, and enhanced automaticity, which characterize the early clinical events in ischemia. During this early period, ATP levels are normal and calcium metabolism appears normal. PMID- 2581500 TI - Induction of hemoglobin F synthesis in patients with beta thalassemia. AB - 5-Azacytidine transiently augments fetal hemoglobin production in patients with beta-thalassemia or sickle cell anemia. This change would probably be beneficial to such patients (e.g. a normal fetal gene product is substituted for a deficient or defective adult gene product) if HbF production could be sustained at high levels for prolonged periods. Even though the clinical use of 5-azacytidine is limited because of its presumed potential to cause cancer, studies with this drug have provided new insights into globin gene regulation and have stimulated the development of other strategies to increase HbF synthesis. PMID- 2581502 TI - Neural pacemakers and rhythmicity. PMID- 2581501 TI - Transport of metabolic substrates by the proximal nephron. PMID- 2581503 TI - Physiological roles of permeable junctions: some possibilities. PMID- 2581504 TI - Ion movements through the sodium pump. PMID- 2581505 TI - Kinetic properties of the plasma membrane Na+-H+ exchanger. AB - The plasma membrane Na+-H+ exchanger is a ubiquitous transport system that participates in diverse cell functions involving the cellular uptake of Na+ or extrusion of H+. It has a tightly coupled 1:1 stoichiometry, has affinity for Li+ and NH+4 in addition to Na+ and H+, and can function in multiple amiloride sensitive exchange modes involving these cations. These general transport properties may be explained by kinetic models involving either cation-hydroxyl cotransport or actual cation-proton exchange. The most important kinetic property of the Na+-H+ exchanger is its greater than first-order dependence on [H+]i. This property enables the Na+-H+ exchanger to play an important role in the regulation of intracellular pH. PMID- 2581506 TI - Mechanism of calcium transport. PMID- 2581508 TI - Nucleotide metabolism and cellular damage in myocardial ischemia. AB - Adenine nucleotide metabolism is greatly altered by myocardial anoxia or ischemia, both of which induce depletion of ATP and of the total adenine nucleotide pool. The depletion occurs at variable rates depending upon the nature of the model and the severity and conditions of the injury. In ischemia, the decrease in both ATP and the adenine nucleotide pool is due to an inadequate rate of production of high-energy phosphate relative to the demand of the heart for energy. In the process of capturing the high-energy phosphate of ADP, AMP is produced via myokinase and is degraded to nucleosides and ultimately to bases. In the early phase of ischemia, ADO and INO are the chief metabolites produced. A small quantity of XAN and large quantities of HX accumulate with time until eventually HX replaces INO as the principal metabolite of the pool. The biology of myocardial ischemic cell damage in the dog heart is summarized with respect to the depletion of ATP and total adenine nucleotide pool. Myocytes can survive with about 25% of the ATP of control tissue but exhibit a variety of defects that persist for minutes to days. At the onset of irreversibility, the dead tissue invariably exhibits virtually no ATP and a 65% or greater depletion in the total adenine nucleotide pool. It is not known whether these changes in ATP and the pool are directly or indirectly related to the development of irreversibility. In any event, the transition to cell death appears to be gradual. PMID- 2581507 TI - Extracellular functions of nucleotides in heart and blood vessels. PMID- 2581510 TI - Immunosuppression. Postoperative management of heart transplant recipients. PMID- 2581509 TI - [Effect of the combined use of dextran sulfate and double-stranded RNA on interferon production]. AB - The studies were performed on CBA mice. It was shown that polynucleotide inductors (poly I-poly C, RFf2 and poly G-poly C) stimulated production of interferon with a peak attained 4-6 or 24 hours after the induction. Intraperitoneal injection of dextran sulfate in a dose of 200 micrograms/m induced production of interferon in small amounts (80-120 units). The production peak was observed in 12 hours. The combined use of dextran sulfate and the polynucleotide inductors provoked an increase in the interferon production. The effect was of a synergistic nature. The cells of the immunocompetent system were the target of the dextran sulfate effect in the host, which was shown experimentally with a culture of mouse lymphocytes. PMID- 2581511 TI - Use of chicken cell line LSCC-H32 for titration of animal viruses and exogenous chicken interferon. AB - The chicken embryo cell line LSCC-H32 was tested for the propagation and titration of several animal viruses of the families Toga-, Reo-, Rhabdo-, Herpeto , Orthomyxo-, Paramyxo-, and Poxviridae and compared with secondary chicken embryo cells. The LSCC-H32 cells were demonstrated to be as susceptible for most of the tested viruses as were secondary chicken embryo cells. Both produced comparably sized virus plaques. The titers of Sindbis and Semliki Forest viruses in LSCC-H32 cells were 5- to 40-fold higher than in secondary chicken embryo cells or BHK-21 cells, respectively. Furthermore, exogenous chicken standard interferon was titrated in the LSCC-H32 cells, and a 50% plaque titer reduction of the challenging vesicular stomatitis virus was achieved by 0.12 IU of a standard chicken interferon preparation. Endogenous chicken interferon could not be induced by treatment of the cells with polyinosinic acid-polycytidylic acid. Due to its high plating efficiency and metabolic activities, the LSCC-H32 cell line provides a useful cell system for the titration and large-scale production of the tested animal viruses and for the titration of exogenous chicken interferon. PMID- 2581512 TI - [Preoperative chemotherapy of testicular cancer and Wilm's tumor]. AB - Of the various urogenital malignancies, preoperative chemotherapy is most effective for testicular cancer and Wilms' tumor. The most effective treatment regimens for advanced nonseminomatous testicular tumors employ vinblastine, CDDP and bleomycin and adjunctive surgery. Another effective chemotherapy regimen is combination of vinblastine, actinomycin D, bleomycin, cyclophosphamide and CDDP presented by MSKCC. Available pretreatment with 4 courses of platinum, vinblastine and bleomycin before any surgical treatment in those with massive bulk metastatic disease seems to provide the most effective cytoreduction and best survival. Donohue has shown that in a primary chemotherapy group, there is only 20% active carcinoma after primary chemotherapy, whereas in a salvage chemotherapy group there is approximately 50% active carcinoma at surgery. It must therefore be emphasized that complete remission should be obtained by primary chemotherapy and adjunctive surgery. In Wilms' tumor preoperative chemotherapy with vincristine and actinomycin D should be given. PMID- 2581514 TI - [Technique for the karyotype analysis]. AB - Techniques for the karyotype analysis in the man and some laboratory animals are described in the present chapter. The international systems for the representation of the standard karyotypes in these materials due to the conventional and the several banding stainings are also introduced. PMID- 2581513 TI - [Phase II trial of peplomycin in non-Hodgkin's lymphoma]. AB - Seventeen patients with malignant lymphoma were entered into a phase II study of peplomycin (PEP) to determine the efficacy of the drug. There were 8 males and 9 females with a median age of 64 yrs (range 3-74 yrs) and a median PS 3 (range 2 4). Three of these were children. At first PEP was given intermittently and intramuscularly (8 cases) at a dose of 10 mg every one (3 cases) or two (5 cases) weeks, and then intravenously by 22-hr continuous infusion (9 cases) at a dose of 5 mg per day for 5 days. Mean cumulative dose was 78 mg. Objective responses were obtained in 6 patient (35%). CR lasting 4 weeks was obtained in one patient with diffuse mixed-type lymphoma. Five patients, one with diffuse medium-sized cell type and 3 with diffuse large cell type, had PR, lasting 6, 7, 7, 9, and 50+ weeks, respectively. Pulmonary fibrosis was found in two patients on autopsy and interstitial pneumonia in two patients clinically. Temporary high fever occurred in 7 patients, stomatitis in 3 patients and anorexia in 3 patients. PMID- 2581515 TI - [Preoperative chemotherapy for head and neck cancer]. AB - The authors have studied preoperative chemotherapy for head and neck cancer since 1963, focusing on intra-arterial chemotherapy. The results obtained revealed that preoperative chemotherapy played an important role in the improvement of 5-year survival in maxillary sinus carcinoma and tongue carcinoma. However, functional and cosmetic damage after radical surgery has newly energed as problems to be resolved. The appearance of cisplatin has raised an important the level of effectiveness of cancer chemotherapy in recent years. Since the combination of cisplatin and bleomycin analogs revealed a remarkable synergistic effect in experimental chemotherapy, it has been used clinically as preoperative or preradiation chemotherapy for advanced Stage III and IV head and neck cancer. Under the above-mentioned circumstances, treatment for head and neck cancer has undergone various changes over the past twenty years. At present it is no exaggeration to say that the period in which dependence was placed on only surgery and/or radiation is over. The authors would like to emphasize that preoperative chemotherapy should be carried out as a part of multidisciplinary approach under a new concept of neo-adjuvant chemotherapy which includes not only preoperative chemotherapy but also preradiation chemotherapy. The role of preoperative chemotherapy, its current status and future prospects are discussed in this paper, looking back on the history of chemotherapy for head and neck cancer. PMID- 2581516 TI - [Structural, ultrastructural and cytochemical study of the mesonephros in the chick embryo]. PMID- 2581517 TI - Effective palliation of malignant biliary duct obstruction. AB - The efficacy of palliative biliary decompression by operative and percutaneous methods was evaluated in 106 patients with unresectable malignancies obstructing the biliary system. Seventy patients had operative and 36 had percutaneous decompression. Primary malignancies of the pancreas and bile ducts were most common. Percutaneous transhepatic decompression was achieved beyond the site of obstruction in 72% of patients. Overall hospital mortality was 25% for patients having percutaneous catheter decompression and 17% for those patients operated upon. Early postoperative death was significantly related to: (1) age greater than 70 years; (2) preadmission weight loss greater than 15 pounds; (3) prothrombin time prolonged more than 2.5 seconds; and (4) hepatic metastases. Major complications were encountered in 56% of survivors of percutaneous drainage and 36% of those surviving operation. Intubation of the bile ducts due to inability to bypass the obstruction at operation was associated with the highest mortality (50%) and morbidity (86%). Mean survival was 14 months after operation, compared to 5 months after percutaneous decompression. The authors concluded that percutaneous decompression of the biliary tree is useful palliative treatment for those patients with proximal biliary obstruction due to malignancy when estimated operative risk is high, but operative decompression offers most patients the opportunity for longer survival with lower ultimate mortality and morbidity. PMID- 2581518 TI - Assessment of treatment of intrahepatic malignancies using chemotherapy via an implantable pump. AB - Thirty patients in whom an implantable pump was used for hepatic arterial perfusion of chemotherapeutic agents to treat hepatic malignancy were evaluated. Three patients with primary hepatocellular carcinoma demonstrated less than 50% reduction in tumor size. One patient with metastatic gastric carcinoma and one patient with metastatic islet cell carcinoma also showed a decrease of less than 50% in the size of the tumor mass. Among the 25 patients with metastatic carcinoma from the colon or rectum, 23 had elevated carcinoembryonic antigen (CEA) levels before surgery and 75% of these revealed a reduction of at least 50%. Only three of 20 patients followed with sequential imaging studies showed a 50% decrease in the size of the tumor mass. No increase in the duration of survival could be defined when the treated patients were compared with 13 patients who had not received chemotherapy. The pump functioned well in all patients, but 77% showed signs of toxicity. This experience, coupled with a review of the literature, suggests that the procedure should be regarded as experimental and should not be applied liberally until a definite benefit can be demonstrated. PMID- 2581519 TI - The pathogenesis of acute pancreatitis. The source and role of oxygen-derived free radicals in three different experimental models. AB - Recent experimental work has suggested that oxygen-derived free radicals may play an important role in initiating the early capillary injury in acute pancreatitis. Data from models of ischemic injury in other organs have suggested the enzyme xanthine oxidase is important in generating oxygen-derived free radicals. The present study was performed to determine whether xanthine oxidase is the source of free radical production in experimental pancreatitis. Utilizing the isolated, perfused, ex vivo canine pancreas preparation, three models of pancreatitis were initiated with (1) free fatty acid infusion (FFA), (2) partial duct obstruction and secretin stimulation (POSS), and (3) ischemia (ISCH). In each model, during a 4-hour perfusion, edema developed, weight gain occurred (FFA 120.6 +/- 21.1 gm; POSS 44.5 +/- 6.9 gm; ISCH 63.3 +/- 14.0 gm), and the serum amylase became elevated (FFA 1827 +/- 397 u/dl; POSS 10,171 +/- 1487 u/dl; ISCH 1860 +/- 365 u/dl). When the xanthine oxidase enzyme inhibitor allopurinol was added to the perfusate prior to the 4-hour perfusion, edema formation was absent or minimal, weight gain was significantly less (FFA 15.2 +/- 2.5 gm p less than 0.05; POSS 8.8 +/- 2.7 gm p less than 0.001; ISCH 12.3 +/- 2.8 gm p less than 0.01), and the amylase remained normal or the elevation was significantly decreased (FFA 996 +/- 189 u/dl p less than 0.05; POSS 3021 +/- 1074 u/dl p less than 0.001; ISCH 993 +/ 214 u/dl p less than 0.002). These data confirm that oxygen-derived free radicals play an important role in the pathogenesis of experimental acute pancreatitis, and suggest that the enzyme xanthine oxidase may well be the source of their production. PMID- 2581520 TI - A prospective study of hyperamylasemia and pancreatitis after cardiopulmonary bypass. AB - General surgical complications after cardiopulmonary bypass (CPB) are infrequent but serious. No prospective studies have evaluated their incidence. We analyzed in such a study 135 patients who were to undergo CPB. Among these 135 patients, an abdominal complication developed in 6.6%; it contributed to 2 of the 5 deaths. Postoperative hyperamylasemia was found in 36% of patients, but only 2 had overt pancreatitis. The hyperamylasemia was not due to the salivary component, pulmonary complications, or prolonged CPB (r = 0.22). A gastrointestinal hemorrhage occurred in 7 patients. No patients had acute cholecystitis. We conclude that abdominal complications are more frequent than reported in retrospective studies, and result in significant morbidity and mortality. Postoperative hyperamylasemia is common but usually is not associated with untoward morbidity or mortality. PMID- 2581522 TI - Fibrous bodies in growth hormone-secreting adenomas contain cytokeratin filaments. AB - Fibrous bodies in growth hormone-secreting adenomas were studied by immunocytochemistry using an anti-cytokeratin antiserum. Fibrous bodies are a feature of acidophil and chromophobe adenomas and are usually associated with acromegaly. Ultrastructural examination revealed round juxtanuclear filamentous aggregates, composed of 8-nm filaments and other organelles. This study demonstrated that the intermediate filaments of fibrous bodies belong to the cytokeratin class. The etiology and significance of these filamentous aggregates remain obscure. PMID- 2581521 TI - Platelet inhibitors and hydroxyethyl starch: safe and cost-effective interventions in coronary artery surgery. AB - This study evaluated the cost-effectiveness and clinical safety of utilizing hetastarch in pump prime solutions and for colloid replacement postoperatively in conjunction with the platelet inhibitors, aspirin and Persantine (dipyridamole). Sixty-four adult patients undergoing a coronary artery bypass operation were divided into two groups. Group 1 (N = 32) received only Persantine (75 mg three times a day) on the day prior to operation. Group 2 (N = 32) received the same Persantine dose plus aspirin (325 mg). In both groups, aspirin and Persantine were continued postoperatively and hetastarch was used as the colloid of choice. All patients were evaluated for blood loss, coagulation profiles, cost of blood and colloid replacement, and clinical course. Group 2 patients demonstrated significantly greater blood loss (p less than 0.05) but the same postoperative coagulation profiles as Group 1. The transfusion requirement (3.6 units versus 1.3 units) and cost basis ($252 versus $91) for patient care were higher in Group 2. Hetastarch had no effect on blood loss and was not associated with any adverse clinical reactions. Annual institutional savings based on utilization of hetastarch were calculated at $33,500 to $40,500 per 500 patients. We conclude that preoperative administration of aspirin (325 mg) is associated with increased perioperative blood loss and higher patient costs, two variables not demonstrable with Persantine only. Use of hetastarch combined with postoperative platelet inhibition was clinically safe and was a cost-effective method of colloid replacement. PMID- 2581523 TI - Stromal and nuclear markers for rapid identification of pituitary adenomas at biopsy. AB - We tested fluorescent and light microscopic markers to improve recognition of pituitary adenomas at biopsy. The optimal reagent was 100 mg/L of fluoresceinated Ricinus communis agglutinin 120 (RCA 120) lectin plus 3 mg/L of propidium iodide. The refrigerated solution was immediately available for use on routine frozen sections. The sections were stained for one minute and viewed immediately after they were rinsed with saline and coverslips applied. Fluorescein-labeled RCA 120, which binds galactose, localized vascular stroma. Propidium iodide, which binds nucleic acids, stained nuclei. Stromal configuration, nuclear morphology, and cell to stroma ratio were illuminated and used to distinguish adenoma from adenohypophysis. We also describe a method utilizing peroxidase-conjugated RCA 120 that demonstrates the same features by light microscopy. Fluoresceinated RCA 120-stained vessels and stroma of routinely processed material more reliably than hematoxylin-eosin or labeled antibody to fibronectin and faster than peroxidase conjugated RCA 120 or the rapid method for reticulin. PMID- 2581524 TI - Leukocyte tubuloreticular inclusions in Reye's syndrome. AB - Tubuloreticular inclusions (TRI) have been observed in the rough endoplasmic reticulum of blood lymphocytes and monocytes in two cases of Reye's syndrome initiated by influenza infections. Tubuloreticular inclusions are seen in these mononuclear leukocytes during the acute phase of illness, but not during convalescence. Since TRI have been demonstrated in peripheral mononuclear leukocytes in patients with acquired immunodeficiency syndrome, systemic lupus erythematosus, and certain viral infections including T-cell leukemia, it may be that the finding of TRI in Reye's syndrome reflects a viral infection and/or immune dysfunction, if such association is not proved to be fortuitous. PMID- 2581525 TI - Frequency of intratubular germ cell neoplasia with invasive testicular germ cell tumors. Histologic and immunocytochemical features. AB - Intratubular germ cell neoplasia (ITGCN) has been regarded as the preinvasive stage of testicular germ cell tumors. We evaluated its frequency in 53 testicular germ cell tumors and determined whether immunohistochemical stains for alpha fetoprotein, human chorionic gonadotropin, carcinoembryonic antigen, and ferritin demonstrated an advantage in its detection in comparison with hematoxylin-eosin and periodic acid-Schiff (PAS) stains. Residual seminiferous tubules were found at the periphery of the invasive neoplastic foci in 47 cases. Intratubular germ cell neoplasia was detected in several or multiple seminiferous tubules in 46 cases (98%). Exquisite localization of PAS-positive intracellular granules was present in all but one case of ITGCN. Focal immunocytochemical positivity for human chorionic gonadotropin, carcinoembryonic antigen, and ferritin was noted in 2.3% of cases. We conclude that ITGCN is present in most invasive germ cell tumors and the PAS stain is very reliable in its demonstration. Antigenic expression of the proteins that we examined is extremely limited in these primordial germ cells. PMID- 2581526 TI - Alteration in RNA synthesis in the dorsal root ganglia of methylmercury-treated rats. AB - The effect of methylmercury in vivo on the incorporation of 3H-uridine in vitro into RNA of dorsal root ganglia of the rat was examined. Modified methods for the incubation of the tissue and extraction of RNA were applied to adequately determine the rate of RNA synthesis. Methylmercury significantly decreased the RNA content and RNA synthetic activity only in the symptomatic period, while uptake of the precursor into the acid-soluble pool remained unchanged. These results indicate that the previously reported inhibition of protein synthesis in dorsal root ganglia at an early phase of methylmercury intoxication was not due to impairment RNA synthesis in this tissue. PMID- 2581529 TI - Age-dependent changes in inhibitory effect of human sera on phytohemagglutinin (PHA)-stimulated lymphocyte proliferation: its relationship to serum alpha 2 macroglobulin. PMID- 2581528 TI - Antigenic analysis of H4 influenza virus isolates using monoclonal antibodies to defined antigenic sites on the hemagglutinin of A/Budgerigar/Hokkaido/1/77 strain. AB - Three non-overlapping antigenic sites were defined on the hemagglutinin of avian influenza virus A/budgerigar/Hokkaido/1/77 (H4N6) by competitive binding assay of monoclonal antibodies to the virus and comparative antigenic analysis of variants selected with monoclonal antibodies. Antigenic relationship among 25 H4 influenza viruses of different bird origin was examined by ELISA with the monoclonal antibodies to each of defined antigenic sites. Two of the three antigenic sites contained epitopes specific to the H4 influenza viruses of budgerigar and mynah origin, and the remaining site contained an epitope which was cross-reactive with almost all of the H4 influenza viruses. PMID- 2581527 TI - Numerical comparative serology of the Bhanja antigenic group (Bunyaviridae). AB - Antigenic relationships between the two known members of the Bhanja serogroup (Bhanja virus, 7 strains; Kismayo virus, two strains) were studied by a plaque reduction cross-neutralization test in Vero cells, using hyperimmune mouse sera. The results were then subjected to a cluster analysis, which showed (in the form of a dendrogram) a considerable antigenic difference between the two viruses. Within Bhanja virus, the European isolates from Haemaphysalis punctata or H. sulcata ticks were antigenically indistinguishable, while the strains isolated in Africa and Asia from other tick species differed slightly from the European strains and also from each other. PMID- 2581530 TI - Interferons in oncology. PMID- 2581531 TI - CSF monoamine metabolite levels in Alzheimer's and Parkinson's disease. AB - Levels of the monoamine metabolites homovanillic acid (HVA), 5 hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in lumbar CSF from 32 patients with a clinical diagnosis of Alzheimer's disease (AD) and from 21 patients with Parkinson's disease (PD). The baseline CSF metabolite values did not differ significantly between the two groups of patients, although HVA levels were lowest in patients with PD and in the more severely demented patients with AD. Levels of all three metabolites increased significantly in both patient groups during probenecid administration, but HVA levels were significantly higher in patients with AD than in patients with PD. Within the AD group, those with the most severe dementia had the greatest rise in MHPG levels. Alterations in monoamine metabolite levels in the CSF detected during probenecid administration aid in the differential diagnosis of neurodegenerative diseases such as AD. PMID- 2581533 TI - Comparative immunogenicity and protective effect against dental caries of a low (3800) and a high (185,000) molecular weight protein in rhesus monkeys (Macaca mulatta). AB - The immunogenicity and protective effect of two peptides derived from the human oral bacterium Streptococcus mutans (serotype c) was examined. Furthermore, the effect of immunization was examined in monkeys previously given fluoride in their diet and which had developed a low incidence of dental caries when offered a human type of diet containing about 15 per cent sucrose. The 3800 peptide streptococcal antigen (SA) has two major antigenic determinants, similar to those in the 185,000 SA I/II. Immunization with 10 (or 1) micrograms of the 3800 SA, made up in an aluminium-hydroxide adjuvant, induced a consistent increase in serum IgG, IgM and IgA antibodies to SA I/II throughout the period of investigation. Salivary-IgA antibodies were only slightly raised. Sequential examination up to 76 weeks showed a significantly lower incidence of dental caries and a lower proportion of Strep. mutans in the immunized compared with sham-immunized, control monkeys. Thus immunization with the 185,000 or 3800 SA can almost completely prevent dental caries in rhesus monkeys which otherwise develop a low incidence of caries. PMID- 2581532 TI - Histamine-release induced by 7S nerve-growth factor of mouse submandibular salivary glands. AB - The 7S nerve-growth factor (7S NGF) purified from mouse submandibular glands induced histamine release from rat-isolated mast cells in the presence of lysophosphatidyl-serine. When 7S NGF was injected intradermally into the rat skin, the vascular permeability increased. This response was abolished by the antihistamine, diphenhydramine. These results show that 7S NGF acts as a potent histamine releaser. PMID- 2581534 TI - The effects of basic and acidic synthetic polypeptides on the adherence of the oral bacteria, Streptococcus mutans and Streptococcus sanguis, to hydroxyapatite. AB - Two basic and two acidic synthetic polypeptides that bind strongly to hydroxyapatite at neutral pH were tested to determine their influence on adsorption of two Streptococcus mutans and two Streptococcus sanguis strains to hydroxyapatite. The adsorption of the strains was significantly enhanced or reduced by the basic and acidic agents, respectively. Study of acidic polypeptides provided evidence of competition between the polypeptides and the bacterial cells for hydroxyapatite adsorption sites. PMID- 2581535 TI - Amylase in parotid saliva of rats after sympathetic nervous decentralization. AB - The marked increase in the amylase secretion that occurs in parasympathetic saliva some days after sympathetic ganglionectomy occurred after decentralization also; hence, it results from lack of impulses from the central nervous system. It occurred whether salivation was evoked by activating muscarinic receptors with methacholine, peptidergic receptors with substance P or physalaemin, or alpha adrenoceptors with phenylephrine. Unilateral operation affected to some degree the contralateral gland also. PMID- 2581536 TI - Effects of intravitreal administration of steroids on experimental subretinal neovascularization in the subhuman primate. AB - To elucidate the role of inflammation in the occurrence of experimental subretinal neovascularization caused by high-intensity laser photocoagulation, we investigated the effects of vitreal infusion of steroids on laser lesions in a primate model. Dexamethasone, with or without triamcinolone, was infused continuously for two weeks through an indwelling cannula system. The animals were followed up clinically for up to eight weeks. The frequency of subretinal neovascularization in the steroid-treated animals was significantly lower than that in a control group of untreated animals. Although steroids have multiple effects, these results suggest that the inflammatory response, possibly macrophage infiltration, may plan an important role in the occurrence of subretinal neovascularization in our experimental model. PMID- 2581537 TI - Lipid keratopathy in rabbits. An animal model system. AB - Rabbits rendered hypercholesterolemic on a high cholesterol diet while subjected to corneal suture placement to induce neovascularization made useful models for qualitatively and quantitatively studying lipid keratopathy. Forty rabbit eyes were subjected to placement of four sutures located between 1 and 4 mm from the limbus. The neovasculature grew at a constant rate of 0.24 mm/day, unaffected by serum cholesterol levels. Rabbits fed cholesterol prior to surgery were the earliest to display lipid keratopathy, followed by those who began cholesterol feedings on the day of surgery, and last by rabbits who began receiving high cholesterol food seven days following suture placement. A description of the corneal neovascularization process and histopathological and biochemical analyses of the induced lipid keratopathy are presented. PMID- 2581538 TI - Central action of substance P: possible role in reward. AB - A series of studies had revealed a dualistic role of post-trial injections of substance P in affecting avoidance behavior depending on the site of the brain in which it is applied. Based on these data, the hypothesis was formulated that substance P has brain site-dependent rewarding and punishing properties, a possibility which was assessed in rats trained on a modified T-maze task. Injections of substance P into the medial forebrain bundle (100 ng) or medial septal nucleus (500 ng) served as a positive reinforcer for conditioned place preference learning in the T maze. Injections into the amygdala (50 ng) or substantia nigra (100 ng) did not have such reinforcing properties. PMID- 2581539 TI - Agents which decrease intracellular thymidine pools cause an augmentation in human natural killer activity in vitro. PMID- 2581541 TI - Evidence for Ca-mediated inactivation of ICa in dialysed guinea-pig atrial cardioballs. AB - Ca current (ICa) was studied in cultured myocytes from right atria of adult guinea-pigs (cardioballs) by means of single low-resistance patch pipettes. K currents were blocked by dialysis of the cells with solutions containing Cs+ as main cation and extracellular TEA (70 mM). Under this condition membrane currents elicited by voltage clamp pulses of 200 ms in duration from -45 mV (holding potential) are net inward for depolarizations up to +55 mV without detectable contamination by outward current components. The peak inward current (ICa) has a maximum between +5 and +10 mV and reverses around +60 mV. Measurements of ICa tail currents obtained after clamp pulses of increasing duration to more and more positive membrane potentials suggest that ICa inactivation is not genuinely voltage-dependent. PMID- 2581540 TI - Purine nucleotide imbalance in immunodeficiency disorders. PMID- 2581542 TI - Cardiac membrane currents and energetic state. AB - Adrenaline, cAMP and cAMP-dependent protein kinase modulate the slow inward Ca current by the same basic mechanism, presumably a phosphorylation of membrane proteins. Protein kinase also seems to play a role in the regulation of K outward currents, but not for the transient inward current. PMID- 2581543 TI - Simultaneous measurements of action potentials and contractions in single cultured adult and embryonic heart muscle cells. AB - Using both a microphotometrical technique and conventional microelectrodes, excitation and contractions have been measured simultaneously in spontaneously active and electrically driven isolated cultured heart muscle cells of embryonic chicks as well as adult rats and guinea-pigs. This experimental arrangement makes it possible to measure continuously and with high accuracy, excitation and E.C. coupling at the single cell level. The contraction time course of spontaneously active embryonic cells and electrically driven adult cells resembles contractions of macroscopic heart muscle preparations against various preloads; mostly a nearly isometric contraction form is found. The effects of various inotropic factors on excitation and contraction (beat frequency, Ca, epinephrine) were studied and it could be shown that the embryonic cells show different features of E.C. coupling. The activity of adult cells resembles very strongly that characteristically found in macroscopic preparations. This proved the feasibility of the method in studies of cardiac E.C. coupling at the single cell level. PMID- 2581544 TI - The two components in the shortening of unloaded ventricular myocytes: their voltage dependence. AB - In isolated myocytes from mammalian ventricles a fast and a slow component in the contractile response to depolarizing voltage clamp steps were identified. The potential dependence of the slow component was identical to the activation curve of iCa. The fast component, however, remained at its maximal amplitude at potentials positive to +10 mV (up to +100 mV), in which potential range iCa declined and eventually disappeared. The results suggest that the slow component may be activated by Ca++ entering through sarcolemmal Ca channels, whereas the fast component depends on Ca release from intracellular sites and may depend on both Cai and voltage. PMID- 2581545 TI - Temperature dependence of verapamil action. AB - Ca2+-tolerant ventricular myocytes from adult rats were electrically stimulated. The maximal contraction frequency (fm) was determined at different temperatures. In drug-free Tyrode solution, fm follows the Arrhenius equation from 7 to 39.5 degrees C. However, verapamil introduces a discontinuity around 27 degrees C into the Arrhenius plot of fm. Above this transition temperature the calcium antagonist lowers fm more pronouncedly than below. Below, a tenfold higher concentration is needed for the same relative effect as at 37 degrees C. It is argued that this finding might be important in cardiac surgery when calcium antagonists are used for cardioplegia at deep hypothermia. PMID- 2581546 TI - Ca-tolerant guinea-pig ventricular myocytes as isolated by pronase in the presence of 250 microM free calcium. AB - A new method to isolate adult cardiocytes with pronase in the presence of 250 microM free calcium was developed. Ultrastructural and electrophysiological properties of these cells were investigated. It is shown that by this method normal calcium-tolerant cells can be obtained. PMID- 2581547 TI - Determination of isolated myocyte viability: staining methods and functional criteria. AB - Single ventricular cells tolerant to physiological levels of calcium have been successfully isolated from adult rat heart. These cells exhibit morphological as well as functional characteristics of the intact myocardium. Under anaerobic incubations either in the absence of extracellular calcium or in the presence of 6% PEG, myocytes excluded Trypan blue despite severe derangements in biochemical functions. We suggest that Trypan blue entry may be a rather insensitive criterion of cell injury. We recommend the combination of rod-shape morphology, ATP levels and the ability to contract under external pacing as alternative simple tests of cell viability. PMID- 2581548 TI - Sarcolemma-bound calcium. Its importance for cell viability. AB - We report the presence of a sarcolemma-associated Ca2+-pool in the intact myocardium and isolated ventricular myocytes of the rat. Ca2+-deposits, which are visualized in the electron microscope as 20 nm thick particles, could be demonstrated when fixation of the tissue was performed in the presence of high inorganic phosphate and most probably represent stable Ca2+-acidic phospholipid phosphate complexes. Various pathophysiological conditions all leading to intracellular Ca2+-overload and compromising myocardial cell viability were imposed and the distribution of Ca2+ was assessed. It was found that in all these conditions cellular Ca2+-overload was preceded or at least accompanied by a loss of sarcolemma-associated Ca2+-deposits. It is concluded that this Ca2+, possibly bound to acidic phospholipids of the sarcolemmal bilayer, plays a role in the maintenance of sarcolemmal integrity. These cytological observations support a concept previously proposed by Langer and his group on the controlling role of membrane Ca2+ in the overall cellular Ca2+-homeostasis. PMID- 2581549 TI - Surface antigens of adult heart cells and their use in diagnosis. AB - The mapping of immunologically relevant epitopes of the myolemma, sarcolemma and endothelium are prerequisites for the analysis of humoral and cellular effector mechanisms. Mapping was carried out by monospecific anticollagen and anticytoskeleton antibodies, monoclonal antibodies against the surface of white blood cells and by lectins which bind to specific sugars on membranes. Characteristic differences between myolemma, sarcolemma and endothelium could be defined. In patients with perimyocarditis and postmyocarditic cardiomyopathy antibodies directed against the myolemma were detected. They are cytolytic in the presence of complement and cross-reactive to the causative viral agents. Furthermore lymphocytotoxic effector mechanisms could be demonstrated in vitro in one third of patients with AMLA-negative primary dilated cardiomyopathy. PMID- 2581550 TI - Electrophysiological properties of isolated ventricular myocytes. AB - There is no doubt that major advances have been made in cardiac electrophysiology using single heart cells. Accurate analysis of rapid inward sodium current and the second inward current carried by calcium has resulted in a major re examination of the steps involved in excitation-contraction coupling in the heart. Future work using glass microelectrodes, suction pipettes and patch pipettes will yield a vast amount of information highly relevant to mechanisms involved in the initiation of the heartbeat. PMID- 2581551 TI - The effect of cyanide on the K-current in guinea-pig ventricular myocytes. AB - The mechanism of the shortening of the cardiac action potential by cyanide was studied in guinea-pig ventricular myocytes using a two micro-electrode voltage clamp technique. It is shown that the shortening can be counteracted by glucose and is due to a marked increase in K conductance. PMID- 2581552 TI - Measurements of single-channel currents in the membrane of isolated cells: ATP dependence of K+-channels. AB - Single-channel currents in ventricular cells of guinea-pig hearts were recorded by the patch-clamp technique. An inwardly rectifying K+-current was found in cell attached membrane patches. Patches could be isolated from the cell exposing the cytoplasmic face of the membrane directly to the bathing solution. After isolation, the same current as in cell-attached patches was seen if the bath contained 4 mM ATP. Without ATP, this current disappeared and another channel of larger conductance and different kinetics was activated. Currents through the latter channel were also seen in cell-attached patches after poisoning the cells by DNP. It is suggested that the ATP-dependence of the observed membrane channels mediates the increase of potassium conductance after metabolic inhibition. PMID- 2581553 TI - [Differentiation of animal species of heat-sterilized meat using isoelectric focusing and subsequent silver staining]. PMID- 2581555 TI - Modulation by dexamethasone of the pyruvate dehydrogenase-complex activity in 3T3 L1 adipocytes. AB - Chronic exposure of 3T3-L1 pre-adipocytes to dexamethasone plus 3-isobutyl-1 methylxanthine (IBMX) with or without insulin caused a significant increase in the specific activity of 'total' pyruvate dehydrogenase complex (PDC) and in the percentage of the 'active' form of the complex compared with cells exposed to a chronic insulin treatment or an acute treatment (2 days) with dexamethasone plus IBMX. In acute-drug-switch-over experiments, dexamethasone also caused an increase in the percentage of 'active' PDC in 3T3-L1 adipocytes. The results show that, in 3T3-L1 adipocytes, dexamethasone, even in the absence of insulin, increases the proportion of PDC in its 'active' form. The mechanism of the dexamethasone effect remains to be investigated. PMID- 2581556 TI - A new, rapid, method for preparation of dispersed pancreatic acini. AB - A new method for the preparation of pancreatic acini is described. The method is simple and much more rapid than previously described techniques, the time required for preparation of pancreatic acini being 20 min from removal of the pancreas. Acini prepared with this method perform in a superior manner when stimulated by either caerulein or secretin. Thus this new technique would be ideal for use in binding and secretion studies. PMID- 2581557 TI - Stereospecific modulation of the calcium channel in human erythrocytes by cholesterol and its oxidized derivatives. AB - To study the effect of cholesterol and its pathophysiologically important oxidized derivatives (OSC) on the calcium entry channel, the human red blood cell was used as a model system. The calcium ejecting adenosinetriphosphatase (ATPase) was inhibited by vanadate. The cells were loaded with OSC at concentrations between 1.25 X 10(-5) and 25 X 10(-5) mol/l. 22-Hydroxycholesterol, cholestan-3 beta,5 alpha,6 beta-triol, 5 alpha-cholestan-3 beta-ol,3 beta,5 alpha dihydroxycholestan-6-one and 3 beta-hydroxy-5 alpha-cholestan-7-one stimulated 45Ca2+ influx by up to almost 90%, whereas 25-hydroxycholesterol, 7 beta hydroxycholesterol, 20 alpha-hydroxycholesterol and 7-oxocholesterol inhibited influx by up to 75%. Both stimulation and inhibition were dependent on the amount of OSC incorporated into the membrane. More than 90% of the total modification of calcium influx by OSC was accounted for by an influence on the nitrendipine inhibitable part of influx. Enrichment of cholesterol in the membrane greatly stimulated, and cholesterol depletion inhibited, Ca2+ influx. These results demonstrate that cholesterol and its oxidized derivatives are able to modulate the calcium channel in human red blood cells in a highly stereospecific manner. PMID- 2581558 TI - Role of Ca2+ in pyruvate dehydrogenase interconversion in brain mitochondria and synaptosomes. AB - The steady-state content of active (dephospho) pyruvate dehydrogenase (PDHA) of suspensions of coupled rat brain mitochondria oxidizing succinate was found to be markedly increased with increasing free Ca2+ ion concentration of the medium, with a half-maximal effect at 10(-6.43) M Ca2+. Other ions were present in these studies at concentrations appropriate for the cytosol. Depolarization of the plasma membrane of synaptosomes caused an increase in the steady-state content of PDHA, with veratridine giving a larger increase than depolarization by 33 mM-KCl. Values were 68 +/- 1% (n = 13) and 81 +/- 1% (n = 19) of maximal activity, for control incubations and incubations in the presence of 30 microM-veratridine, respectively. Measurements of cytosolic free Ca2+ concentrations ([Ca2+]cyt.) in these suspensions of synaptosomes, with the use of the fluorescent Ca2+-indicator Quin-2, indicated an increase on depolarization, with the change due to 30 microM veratridine being larger in extent than that due to 33 mM-KCl. Values were 217 +/ 21 nM (n = 15), 544 +/- 48 nM (n = 15) and 783 +/- 75 nM (n = 14) for control, KCl-depolarized and veratridine-depolarized synaptosomes respectively. Experiments in which synaptosomes were treated with Ruthenium Red, an inhibitor of mitochondrial Ca2+ uptake, gave much lower resting contents of PDHA (42 +/- 2% of maximal), but failed to prevent totally an increase on depolarization. Addition of an excess of EGTA to the synaptosomal suspension just before the addition of veratridine resulted in a partial diminution in the response of PDHA content. Parallel studies with Quin-2 indicated no increase in [Ca2+]cyt. on addition of veratridine, under these conditions. Thus an increase in [Ca2+]cyt. forms only a part of the mechanism whereby pyruvate dehydrogenase interconversion responds to depolarization. A decrease in the ATP/ADP ratio may also be important, as inferred from the results of experiments with ouabain, which inhibits the Na+ + K+-dependent ATPase. PMID- 2581559 TI - Monoclonal antibodies recognizing epitopes carried on both glycolipids and glycoproteins of the human milk fat globule membrane. AB - The molecules of the human milk fat globule membrane (MFGM) which bind four murine monoclonal antibodies (LICR LON M3, M8, M18 and M24) raised against the human MFGM have been identified. By using 'Western' blotting [Burnette (1981) Anal. Biochem. 112, 195-203] it was shown that each antibody reacted with a different set of proteins. M3 and M24 were similar in their pattern of reaction with the membrane proteins, but were quite distinct from M8 and M18, which also differed from each other. Glycopeptides prepared from the MFGM by exhaustive Pronase digestion were able to inhibit partially the binding of M3 and M24, and prevent totally the binding of M8 and M18, to the MFGM in an enzyme-linked immunoabsorbent assay. Oligosaccharides obtained by the deproteination of human milk also completely inhibited the binding of M3, M18 and M24 to the MFGM. However, the binding of M8 was not inhibited by these saccharides, and therefore M8 may not be recognizing a simple carbohydrate determinant. By using an enzyme linked assay, M8 and M18 were shown not to bind to MFGM glycolipid, whereas M3 and M24 did, and this was confirmed by overlaying thin layer chromatograms of MFGM lipids with these antibodies. Both M3 and M24 showed a similar complex pattern of reaction, binding to more than one glycolipid moiety. By these means all four antibodies have been shown to react with antigens which involve carbohydrate side chains carried on different proteins, and two were also shown to react with such determinants on glycolipids. PMID- 2581554 TI - Regulation of cell proliferation and differentiation by interferons. PMID- 2581561 TI - Some biochemical properties of human breast tumor sialyltransferase. AB - Sialyltransferase activity in normal human breast tissue and tumors was investigated with lactose, desialylated fetuin, and bovine submaxillary mucin as the acceptors. While microsomal preparations from the normal tissue showed little or no sialyltransferase activity toward these acceptors, tumors showed elevated enzymic activities. Tween-20 at 0.5% concentrations stimulated sialic acid transfer to all three acceptors. Another nonionic detergent, Triton X-100, stimulated asialo fetuin sialyltransferase activity while inhibiting activity toward asialo BSM and lactose. Interestingly, lysolecithin, a normal cellular constituent which possesses detergent properties also had an effect similar to that of Triton X-100. Thermal denaturation curves of enzymic activity toward asialo BSM, however, resembled those seen with asialo fetuin as the acceptor. Kinetic studies showed that at acceptor concentrations of 500 micrograms each, sialyl transfers to asialo fetuin, asialo BSM, and lactose showed apparent Km values of 50, 60, and 300 microM, respectively. At CMP-sialic acid concentrations of 300 microM, the Km values for the above acceptors were 25, 15, and 5000 microM. PMID- 2581560 TI - Location of an epitopic site on epiglycanin by molecular immunoelectron microscopy. AB - Antibodies of the IgM type present in rabbit anti-epiglycanin antiserum were purified by (NH4)2SO4 precipitation and by ion-exchange, affinity and gel filtration chromatography. After papain treatment of this fraction, followed by gel filtration, the fraction with highest apparent Mr was incubated with epiglycanin, and the antigen-antibody complexes separated by gel filtration. These were examined by electron microscopy, using rotational shadow casting, and the photographs of the complexes were mapped for the locations of the antibody molecules on the extended epiglycanin molecules. Distribution of the frequency of attachment of immunoglobulin showed a strong tendency toward binding at one end of epiglycanin, suggesting the probable presence of only one epitope, probably a glycopeptide structure containing a beta-D-galactopyranosyl-(1----3)-2-acetamido 2-deoxy-D-galactose chain. PMID- 2581562 TI - The effects of subdiabetogenic streptozotocin doses on rat beta cell volume and functions. AB - The influence of a single i.v. injection of 30 mg/kg streptozotocin (SZ) into female Wistar rats on plasma glucose, pancreatic insulin content, volume and function of the remaining beta-cells has been investigated. 14 days after SZ treatment most animals remained normoglycemic; only about 15% showed permanent hyperglycemia. The pancreatic insulin content in normoglycemic rats was reduced to 30%, whereas in hyperglycemic rats only 6% of control values could be detected. The remaining beta-cell volume was comparable in the two groups, indicating no correlation between pancreatic insulin content and residual beta cell volume. The glucose- and IBMX-stimulated insulin release of islets isolated from normoglycemic cats 14 days after SZ application was not significantly altered whereas the islets insulin content of SZ treated animals was significantly lowered in comparison to controls. PMID- 2581563 TI - Amplification of c-Ki-ras gene and aberrant expression of c-myc in WI-38 cells transformed in vitro by gamma-irradiation. AB - The expression of c-oncogenes was examined with normal human fibroblasts (WI-38) and the cells transformed in vitro by gamma-irradiation (CT-1). The amount of Ki ras-specific mRNA in CT-1 cells was found to be approximately twice that in WI-38 cells. By Southern blot hybridization, the c-Ki-ras 2 gene of CT-1 cells was found to be amplified about two-fold. CT-1 cells have higher levels of c-myc mRNA than normal cells, although the gene dosage and the restriction nuclease pattern of the c-myc gene was the same. The content of c-myc mRNA in CT-1 cells was found to be constitutively high, whereas that in normal cells was increased by serum addition. PMID- 2581564 TI - Vascular receptor binding activities and cyclic GMP responses by synthetic human and rat atrial natriuretic peptides (ANP) and receptor down-regulation by ANP. AB - Biological activities of a variety of synthetic human (h) and rat (r) atrial natriuretic peptide (ANP) and related peptides as assessed by receptor binding and cyclic GMP response, and regulation of vascular ANP receptors were studied in rat aortic vascular smooth muscle cells (VSMC) in culture. alpha-hANP1-28 and alpha-hANP7-28 equally inhibited the binding of 125I-labeled-alpha-hANP to its vascular receptors, whereas Met(O)12-alpha-hANP1-28 was less potent and reduced and carboxymethylated (RCM)-alpha-hANP1-28 was ineffective. rANP5-27 and rANP5-28 were equipotent in receptor binding, whereas rANP5-25 had somewhat less potent effect and rANP8-28 fragment was ineffective. alpha-hANP1-28, alpha-hANP7-28, rANP5-27 and rANP5-28 similarly stimulated intracellular cyclic GMP formation, whereas rANP5-25 showed less stimulatory effect, and RCM-alpha-hANP1-28, Met12 sulfoxide and rANP fragment were ineffective. Pretreatment with unlabeled alpha hANP (3.2 X 10(-9) and 3.2 X 10(-8)M) for 24 hrs resulted in a substantial reduction (55 and 75%) of total receptor number without changing the affinity of ANP receptors. These results suggest that the common ring structure formed by the disulfide bond in the molecule is critical for receptor binding and subsequent biological actions, and that a hydrophobic amino acid located at the position of 12, and (24-26) residues at the C-terminal side, but not (1-6) at the N-terminal side, of the disulfide bridge may play a part in modulating receptor binding and/or biological functions. The present study also indicates "down-regulation" of vascular ANP receptors by homologous ligand. PMID- 2581565 TI - In vitro antigenic reactivity of synthetic lipid A analogues as determined by monoclonal and conventional antibodies. AB - Cross-reactivities of synthetic lipid A analogues with monoclonal and conventional antibodies against Salmonella lipid A were studied. It was shown that the in vitro antigenicity of a synthetic compound 506, beta-(1----6) D glucosamine disaccharide 1,4'-bisphosphate, which is acylated at 2'-amino and 3' hydroxyl groups with (R)-3-dodecanoyloxytetradecanoyl and (R)-3 tetradecanoyloxytetradecanoyl groups, respectively, and has (R)-3 hydroxytetradecanoyl groups at 2-amino and 3-hydroxyl groups, was practically indistinguishable from that of the natural E. coli lipid A preparation, and that both phosphates in positions 1 and 4' as well as ester- and amide-linked fatty acyl residues, particularly 3-acyloxyacyl group, of the glucosamine disaccharide are involved in the cross-reactivity of lipid A as important antigenic determinants. PMID- 2581566 TI - n-Decyl-NHpppA2'p5'A2'p5'A A phosphatase-resistant, active pppA2'p5'A2'p5'A analog. AB - n-Decyl-NHpppA2'p5'A2'p5'A, a gamma-substituted, phosphatase-resistant pppA2'p5'A2'p5'A analog, gives similar rRNA degradation pattern in interferon treated HeLa cell extracts--even at a concentration of 10(-9)M--as the natural compound does. PMID- 2581567 TI - A functional identification of cardiac junctional sarcoplasmic reticulum. AB - Junctional sarcoplasmic reticulum (SR) has been identified in microsomes from canine ventricular muscle by the presence of calsequestrin and ryanodine sensitive Ca2+ release channels. These properties, however, are not common to cardiac cells from all species. Seiler et al (1) have recently described a high Mr polypeptide in canine junctional SR similar to the spanning protein subunits of skeletal muscle triads. We now report the existence of a polypeptide with the same mobility in SR from rabbit ventricular muscle and show that those cardiac membranes can associate with transverse (T-) tubules from rabbit skeletal muscle in K cacodylate medium. We propose that this polypeptide and the reaction with T tubules be considered as criteria for the identification of cardiac junctional SR. PMID- 2581569 TI - Binding of alpha 2-macroglobulin to hepatocytes: mechanism of in vivo clearance. AB - The binding of 125I-labeled human alpha 2-macroglobulin-methylamine to adult rat hepatocytes in primary culture was studied at 4 degrees C. Cells which had been in culture for 4 hours exhibited steady state ligand binding after 1 hour, a receptor number of 22,400 receptors per cell, and a dissociation constant of 0.6 nM. Adult rat hepatocytes exhibited a significant decrease in receptor number with increased time in primary culture with less than 10% of the initial number of receptors remaining after 2 days (p less than 0.01). In autopsy studies of mice injected intravenously with 125I-labeled alpha 2-macroglobulin-methylamine, greater than 90% of the cleared ligand was found in the liver. Autoradiography of the liver demonstrated that 80% of the ligand was cleared by hepatocytes. It is concluded that the hepatocytes are the primary pathway for clearance from the circulation of receptor recognized alpha 2-macroglobulin. PMID- 2581568 TI - Evidence from 23Na NMR studies for the existence of sodium-channels in the brush border membrane of the renal proximal tubule. AB - A fast Na+-exchange is shown to be present in isolated renal brush border membranes. The lower limit of the rate constant for this process, calculated from the 23Na-NMR spectrum is 580 sec-1. The actual exchange rate may be higher. A fast 7Li exchange is also shown to be present in the isolated membrane vesicles. The characteristic overshoot of the Na+ dependent D-glucose cotransport and Na+/H+ antiport can be demonstrated. The fact that neither treatment with papain, nor lowering of the temperature to 5 degrees C affected the 23Na-NMR spectra obtained in the renal brush border membrane vesicles is consistent with the possibility that the fast Na+-exchange occurs through a channel mechanism. PMID- 2581570 TI - Tumor promoter inhibition of cellular binding of somatostatin. AB - Tumor promoting phorbol esters inhibited the binding of 125I-[Tyr11] somatostatin to isolated acinar cells from guinea-pig pancreas. Maximal inhibition reached 69.7 +/- 5% at 1 microM TPA. Receptor affinity was decreased by 2.5-fold without change in binding capacity. The ability of TPA in inhibiting somatostatin binding was decreased in 30 nM Ca2+ medium, abolished at 4 degrees C or in a membrane preparation. The effect of caerulein, a secretagogue which also caused loss of binding, and that of TPA were not additive. We concluded that TPA inhibits somatostatin binding not by binding directly at the active site of somatostatin receptor. TPA may act at a later point than caerulein via a similar pathway to modulate somatostatin receptor affinity. PMID- 2581571 TI - Structural localization of the sequence alpha 235-242 of the nicotinic acetylcholine receptor. AB - Two monoclonal antibodies (mAb 254 and 255) were obtained against a synthetic peptide corresponding to the sequence 235-242 of the alpha-subunit of Torpedo acetylcholine receptor. These mAbs could bind to receptor in native membrane vesicles only when these vesicles were permeabilized, suggesting that the sequence alpha 235-242 is exposed on the cytoplasmic surface of the receptor. Further evidence for the cytoplasmic localization of this sequence was partial competition for binding between these mAbs and mAbs previously demonstrated to bind to the cytoplasmic part of the receptor. A model is proposed which accounts for all the experimental data obtained thus far on the transmembrane orientation of the subunit polypeptide chains. PMID- 2581572 TI - Nonparallel discharge of digestive enzymes from isolated pancreatic acini. AB - The secretion of amylase, trypsinogen, chymotrypsinogen and proelastase from isolated rat dispersed pancreatic acini was investigated in the absence (basal) and presence of two concentrations of CCK8 (50 and 500 pM), carbachol (2.5 and 7.5 microM) and secretin (10 nM and 1 microM). The unstimulated (basal) rate of release of each of the digestive enzymes was essentially the same. However, whereas both doses of CCK8 and carbachol caused a preferential release of chymotrypsinogen over that of amylase and trypsinogen, the magnitude of stimulated release of amylase, trypsinogen and chymotrypsinogen by 1 microM secretin was found to be similar for each of the enzymes. Furthermore, none of the secretagogues caused a significant enhancement in proelastase release. The present data demonstrate that whereas CCK8 and carbachol induce a greater release of chymotrypsinogen over that of amylase or trypsinogen, release of all three enzymes was equally stimulated by secretin from isolated pancreatic acini. PMID- 2581573 TI - Neuropeptide K: isolation, structure and biological activities of a novel brain tachykinin. AB - A 36 amino acid residue peptide, which contains a substance K sequence at its C terminus has been isolated from porcine brain extracts. The primary structure of the peptide, designated neuropeptide K (NPK), was found to be: (sequence; see text) This N-terminally extended form of substance K is present in a high concentration in the brain. The peptide is highly biologically active with regard to gallbladder contraction, protein extravasation, hypotension and bronchial smooth muscle spasm and may act as an additional tachykinin neuromessenger. PMID- 2581574 TI - Major intrinsic polypeptide (MIP26K) from lens membrane: reconstitution into vesicles and inhibition of channel forming activity by peptide antiserum. AB - Bovine and human lens membrane, when reconstituted into lipid vesicles containing oxidized cytochrome C, will mediate the transmembrane passage of ascorbate into the vesicles, where the reduction of cytochrome C is measured spectrophotometrically. This channel forming activity is specifically inhibited by antiserum made against a synthetic octapeptide near the C-terminus of MIP26K. Together, these studies describe a direct and more sensitive assay system for measurement of channel-forming activity of MIP26K, and suggest that the C terminus of this molecule may be particularly important in the regulation of channel formation. PMID- 2581575 TI - Synthetic inhibitors of human leukocyte elastase Part 1--Sulphated polysaccharides. AB - Ten dextran sulphates and six chitosan sulphates of variable Mr and extent of sulphate substitution have been examined for their ability to inhibit human leukocyte elastase (HLE). All were potent partial non-competitive inhibitors of this enzyme, highest activity being obtained with compounds of large molecular weight and maximum sulphate incorporation (Ki = 5.0 X 10(-10)M]. In all cases, the dextran sulphates were more effective inhibitors than chitosan sulphates of similar size and charge, but both classes were inactive against bovine trypsin, chymotrypsin and porcine pancreatic elastase at concentrations less than 10(-4)M. The data suggest that drug binding to HLE occurs by stereospecific electrostatic interactions at site(s) removed from the catalytic reaction centre. PMID- 2581576 TI - Calcium-dependent endoribonuclease of Trypanosoma brucei has a base-preferential affinity to adenylate. AB - The substrate specificity of a calcium-dependent endoribonuclease of Trypanosoma brucei cytoplasm has been further determined. The actions of the enzyme on transfer RNA, ribosomal RNA and various synthetic polyribonucleotides indicate that the enzyme degrades double-stranded as well as single-stranded RNAs; while it preferentially hydrolyses polyribonucleotides having adenylic acid residues, and has a pronounced preference for poly (adenylic acid). Its apparent Michaelis constant (Km) values using different substrates also suggest a base-preferential affinity of the enzyme to adenylate. The relative activity of the ribonuclease against homopolyribonucleotides is poly(A) greater than poly(U) greater than poly(C); while poly(G) is completely resistant to the activity. Poly(A) segments on poly(A)-rich RNA are selectively hydrolyzed by the endoribonuclease. A possible implication of this enzyme in the post-transcriptional modification and turnover of mRNA molecules is suggested. PMID- 2581577 TI - Production and properties of a monoclonal antibody against human epidermal growth factor. AB - A monoclonal antibody against human epidermal growth factor (hEGF) was obtained from a mouse hybridoma cell line. The purified monoclonal antibody from the ascites fluid of a mouse injected with one of the cell lines was specific for hEGF and did not cross-react with mouse EGF (mEGF). Its Kd value for hEGF was 1.4 X 10(-9) M. This monoclonal antibody inhibited the biological activities of hEGF, including its binding to the receptor of BALB/3T3 cells and its stimulation of DNA synthesis in the cells, but did not affect the activities of mEGF. The monoclonal antibody completely inhibited DNA synthesis stimulated by human urine from a patient without a tumor, but only partially inhibited the stimulatory activity in urine from a tumor-bearing patient. PMID- 2581578 TI - Monoamine metabolites: their relationship and lack of relationship to monoaminergic neuronal activity. PMID- 2581579 TI - Release of D-[3H]aspartic acid from the rat striatum. Effect of veratridine evoked depolarization, fronto-parietal cortex ablation, and striatal lesions with kainic acid. AB - The spontaneous and depolarization-evoked release of radiolabeled D-aspartic acid, previously taken up by rat striatal slices, was studied by using a superfusion system. Veratridine (10-50 microM), electrical field stimulation (20 Hz, 1.0 V, 60 sec), and potassium (53 mM) markedly potentiated the release of D [3H]aspartate from striatal slices. The release of L-[3H]glutamate was also increased by veratridine, according to a pattern and time course of release similar to that of D-[3H]aspartate. However, the ratio of D-[3H]aspartic acid release evoked by veratridine over spontaneous levels of release was much higher when compared to that of radiolabeled L-glutamate. Omission of calcium from the superfusion medium almost completely suppressed D-[3H]aspartate release evoked by veratridine or by electrical stimulation whereas high K+-evoked release of the [3H]amino acid was only slightly reduced. However, increasing Mg2+ concentration to 12 mM in the superfusion medium did substantially block D-[3H]aspartate release induced by K+-depolarization. Additional experiments showed that tetrodotoxin (1 microM), a blocker of voltage-dependent Na+ channels, totally abolished veratridine-evoked release of D-[3H]aspartate from striatal slices. Finally, lesion studies showed that unilateral ablation of the frontoparietal cortex was accompanied by a significant decrease in the high-affinity uptake of striatal D-[3H]aspartate and by a large and parallel loss from striatal slices in D-[3H]aspartate release evoked by either veratridine or high K+. In contrast, unilateral injection of kainic acid into the striatum did not influence depolarization-evoked release of D-[3H]aspartate from striatal slices. The findings reported suggest that D-[3H]aspartic acid may be taken up preferentially and then released, in a Ca2+-dependent manner, by veratridine and electrical stimulation from nerve terminals belonging to the cortico-striatal pathway. In addition, the results provide further support for the view that excitatory amino acids may act as neurotransmitters at the cortico-striatal nerve fibers. PMID- 2581580 TI - Hormonal and drug effects on the degradation of human myelin basic protein peptide 43-88 by alkaline proteolytic activity in the rat kidney. AB - The microsomal brush-border fraction of rat renal tissue contains enzymatic activity, optimally active at pH 9, that is capable of degrading human myelin basic protein (BP) peptide 43-88. In the present study, this degradation and the effect on it of selected drugs and hormones were examined further. Of the substances tested, 10(-2) M chloroquine and 10(-5) M ACTH 1-24 were found to be the most effective inhibitors followed by 10(-5) M ACTH 1-39; parathormone, glucagon and insulin were found to be inhibitors an order of magnitude weaker than ACTH 1-24. Hydrocortisone, dexamethasone, maleic acid and ACTH 4-10 were found to have minimal or no inhibitory effect on the peptide degrading activity. Gel filtration of the degradation products indicated that the rate of degradation of BP peptide 43-88 at pH 9 had been retarded by ACTH 1-24. These studies indicate that the clearance and catabolism of this peptide may be altered by available therapeutic agents. PMID- 2581581 TI - Effects of intraventricular injections of 6-hydroxydopamine on amine metabolites in rat brain and urine. AB - The effects in rats of intraventricular injections of 6-hydroxydopamine (6-OHDA) on the urinary excretion 1-3 weeks later of 3-methoxy-4-hydroxyphenethylene glycol (MHPG), 3,4-dihydroxyphenethanol (DHPE), 3-methoxy-4-hydroxyphenethanol (MHPE), p-hydroxyphenylglycol (pHPG), homovanillic acid (HVA) and 3,4 dihydroxyphenylacetic acid (DOPAC) were examined. The excretion of MHPG was decreased to 63 and 71% of control on days 7 and 14, respectively, but had returned to control levels by day 23, even though the brain levels were decreased by 87%. Free and total HVA excretion was reduced on both days 7 and 23, but free and total DOPAC was reduced only on day 7. Based on these data, it can be estimated that about 39% of the free and 46% of the total HVA in urine originates in the CNS. The excretion of conjugated HVA was decreased by 70-80%, but this decrease does not support the notion that the conjugated form of HVA is derived principally from the brain and thus serves as a better marker of brain dopamine metabolism, since the level of this metabolite in the brain was not correspondingly decreased but was instead increased. Urinary DOPAC levels were generally more variable and derived to a greater extent from the periphery; therefore, DOPAC appears to be less suitable than HVA as a marker of brain dopamine. The results also indicate that as much as 35% of the urinary MHPG may originate in the CNS, although compensatory changes in catecholamine metabolism in either the brain or in the periphery may have somewhat influenced this estimate. The results also suggest that at least as much pHPG as MHPG in urine derives from the CNS. The data are consistent with the idea that the neutral dopamine metabolites largely derive from the brain, but the relatively small depletion in their brain levels produced by 6-OHDA prevented the exact proportion being determined accurately. PMID- 2581582 TI - Effects of nitroheterocyclic drugs on macromolecule synthesis and degradation in Trypanosoma cruzi. AB - Nifurtimox and benznidazole, two nitroheterocyclic drugs, inhibited DNA, RNA and protein synthesis, stimulated macromolecular degradation, and stimulated unscheduled DNA synthesis in Trypanosoma cruzi (Tulahuen strain). Significant differences in the mode of action of these drugs could be established and, in every case, nifurtimox was more active than benznidazole. The inhibition of macromolecular synthesis varied with drug concentration, precursor and incubation time. Nifurtimox effect was time dependent and irreversible. When assayed on macromolecular degradation, nifurtimox was more effective on DNA and protein than on RNA, while benznidazole displayed almost the same activity on DNA, RNA and protein. Labeling of RNA with [3H]uridine in the presence of nifurtimox followed atypical kinetics since, depending on incubation time and concentration, RNA degradation prevailed over RNA synthesis. PMID- 2581583 TI - Differential release of serotonin without comparable histamine under diverse conditions in the rat mast cell. AB - Pretreatment of mast cells with various psychotropic agents was shown to permit preferential release of serotonin without substantial release of histamine or massive degranulation. Differential release involved both endogenous, granule stored serotonin, and exogenous radiolabeled serotonin that had been taken up by the cell. This phenomenon occurred in mast cells stimulated to secrete with suboptimal concentrations of the classic mast cell secretagogue compound 48/80, was associated with drugs of several different structures and known mechanisms of action, and could be inhibited by certain prostaglandins. Furthermore, differential release of serotonin occurred in mast cells of retired breeders without the use of drugs or other exogenous agents. Light microscopic studies of mast cells undergoing differential release showed minimal degranulation, indicating that most of the serotonin release did not occur via classic exocytosis. The ability of mast cell to selectively release serotonin, by a mechanism unlike that occurring in allergic anaphylactic secretion, constitutes one of the first instances of differential release from secretory cells, suggests a new mechanism of release of secretory products, and expands the potential role of mast cells in the pathophysiology of the body. PMID- 2581584 TI - Effect of clonidine on the activity of tryptophan hydroxylase from rat brainstem following in vivo or in vitro treatment. AB - In vivo administration of clonidine hydrochloride (Catapres) via tail vein injection produced a rapid increase in brainstem tryptophan hydroxylase activity assayed in vitro under subsaturating conditions of reduced pterin cofactor, 6MPH4. Enzyme activity returned to and remained at control levels about 60 min after treatment with low doses of clonidine (5 micrograms/kg). However, with higher doses of the drug (15 micrograms/kg), enzyme activity fell to below control levels for about an hour. Incubation of brainstem slices with clonidine also produced a dose-dependent increase in enzyme activity. The increase in enzyme activity appears to be mediated indirectly since it was abolished when brain catecholamine levels were depleted by pretreatment with 6-hydroxydopamine 8 days prior to clonidine treatment. The kinetic properties of tryptophan hydroxylase prepared 25 and 90 min after clonidine administration indicate that the initial increase and subsequent decrease in enzyme activity seen under these conditions may be due to changes in apparent Vmax of the enzyme. PMID- 2581585 TI - Effect of phosphodiesterase inhibitors on bradykinin-mediated prostaglandin E2 and cyclic AMP synthesis in renal papillary collecting tubule cells. AB - Isolated rabbit renal papillary collecting tubule cells were used to examine the effects of phosphodiesterase inhibitors on intracellular cyclic AMP and prostaglandin synthesis. Experiments performed on confluent primary tissue cultures demonstrated that bradykinin increases intracellular cyclic AMP by a prostaglandin-dependent mechanism. Phosphodiesterase inhibitors induced a dose dependent decrease in bradykinin-stimulated prostaglandin synthesis. Fifty percent inhibition occurred with approximately 0.7 mM 3-isobutyl-1-methylxanthine (IBMX). Inhibition was found to be reversible. IBMX did not inhibit bradykinin induced prostaglandin synthesis as a result of increased intracellular cyclic AMP. The nonmethylxanthine phosphodiesterase inhibitor RO 20-1724 also reduced bradykinin-stimulated prostaglandin synthesis. IBMX inhibited calcium-ionophore A23187-induced prostaglandin synthesis but did not inhibit arachidonic acid stimulation of prostaglandin synthesis. The data demonstrate that bradykinin increased renal papillary collecting tubule cell cyclic AMP in a prostaglandin dependent manner. Based on the data presented, phosphodiesterase inhibitors act to decrease arachidonic acid availability for prostaglandin synthesis, independent of changes in cellular cyclic AMP content. PMID- 2581586 TI - [Specificity of enzymes of biosynthesis of Salmonella anatum O-antigen for polyprenyl derivatives of different chain length and saturation]. AB - Polyprenyl phosphates of different structure were prepared and their ability to serve as sugar acceptors in the biosynthesis of O-specific polysaccharides of Salmonella anatum was investigated. It was demonstrated that C30-C80-polyprenyl phosphates with unsaturated alpha-isoprene unit were as active as natural acceptor (undecaprenyl phosphate) in this enzymic system. C15- and C100 polyprenyl phosphates of this series were less effective in O-antigen repeating unit formation. Citronellyl and dolichyl phosphates (derivatives of C10- and C105 polyprenols, respectively, with saturated alpha-isoprene unit) were poor substrates. For polymerization of repeating units, the polyprenol chain-length is of utmost importance: its shortening results in a marked drop in the efficiency of respective compounds as substrates. PMID- 2581587 TI - [Synthesis of oligosaccharide fragments of O-specific Shigella flexneri polysaccharides. II. Synthesis of trisaccharide Glc alpha1----3RHa alpha1----2Rha alpha1----OMe and tetrasaccharide GlcNAc beta1----2(Llc alpha1----3)Rha alpha1--- 2Rh alpha1----OMe]. AB - Methyl glycosides of the title linear trisaccharide and branched tetrasaccharide were synthesized by stepwise glycosylation. These oligosaccharides represent the fragments of O-antigenic polysaccharides of Shigella flexneri serotypes 2b, 3a, 5b, and X. PMID- 2581588 TI - Simultaneous determination of homovanillic acid, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid in brain tissue, using a double-column procedure. AB - A double-column procedure for simultaneous determination of homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5 HIAA) in brain tissue was described. These compounds extracted with perchloric acid were adsorbed on Sephadex G-10 in the column. HVA and DOPAC were desorbed from Sephadex G-10 with 0.01 N HCl and then retained on QAE-Sephadex A-25 (acetate form) placed beneath the Sephadex G-10 column. HVA and DOPAC were eluted with small volume of 0.2 mol/l NaCl. 5-HIAA remaining on the Sephadex G-10 was eluted with 0.05 mol/l phosphate buffer at pH 7.5. Each substance was determined fluorometrically. The recovery rates of HVA, DOPAC and 5-HIAA were more than 80, 80 and 85%, respectively. Effects of oxypertine on dopamine (DA) neurons in the rat brain were investigated using the method described here. Oxypertine caused marked increases in the levels of HVA and DOPAC in cortex and striatum of the rat brain, without any obvious change in the level of 5-HIAA after the intraperitoneal administration of 10 mg/kg oxypertine. These findings suggest that the favorable antipsychotic action of oxypertine may be due not only to a marked reduction in brain norepinephrine level, but to a blockade of DA receptors. PMID- 2581589 TI - The influence of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on the levels of dopamine, serotonin and their metabolites in the caudate nucleus of the rat. AB - Until now it has been generally believed that N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (NMPTP) could induce a Parkinson-like syndrome only in man and in the rhesus monkey, a syndrome which begins with degeneration of the nigrostriatal system and is accompanied by a marked reduction in dopamine levels in the caudate nucleus. Rats, guinea pigs and cats subjected to comparable doses of NMPTP showed neither motor nor biochemical disturbances. In the present study it could be demonstrated, however, that long-term treatment of rats with a total dose of 116.9 mg NMPTP/kg brings about changes in the metabolism of the biogenic amines dopamine and serotonin in the caudate nucleus. The treatment reduced the dopamine and homovanillic acid levels to about 50% of their normal values, 3.4 dihydroxyphenylacetic acid also to 60% of the control levels. These experiments demonstrate that NMPTP, given in appropriate doses for a sufficient time, is capable of producing neurodegenerative changes in rats as well. This implies that the rat is a suitable experimental animal for studies with NMPTP. PMID- 2581590 TI - Studies on hydroxyethyl starch. Part I: Molecular characterization by size exclusion chromatography coupled with low-angle laser light scattering. AB - Two commercially available hydroxyethyl starch (HES) preparations (in clinical use as plasma expanders) specified with Mw = 450,000/MS = 0.7 and Mw = 200,000/MS = 0.5, respectively, and three experimental HES-samples (supposingly similar to the commercial product with the specification 450,000/0.7, except of one with MS = 0.5) were studied. The latter were prepared via acid or enzymatic hydrolysis of waxy-maize starch. Each of the samples was characterized by its intrinsic viscosity and molar substitution, and was studied with low-angle laser light scattering (LALLS) and with size exclusion chromatography (SEC) coupled with LALLS. The weight-average molecular weight Mw of the commercial samples was found to be 60-80% higher than the value given in the product declaration. This discrepancy can be explained by the argument that previous measurements were not carried out at sufficiently small scattering angles to enable reliable extrapolation to zero angle. The calibration functions Mw(v) of the individual HES-samples measured by SEC/LALLS-coupling are identical over a broad range of the elution volume v and are used for calibration of conventional SEC in a subsequent paper. The small, but detectable differences in the Mw(v)-functions indicate interesting differences between these HES-preparations with respect to the effective hydrodynamic density of the branched HES-molecules. PMID- 2581592 TI - [Behavioral development of children recovering from severe malnutrition]. PMID- 2581591 TI - Studies on hydroxyethyl starch. Part II: Changes of the molecular weight distribution for hydroxyethyl starch types 450/0.7, 450/0.5, 450/0.3, 300/0.4, 200/0.7, 200/0.5, 200/0.3 and 200/0.1 after infusion in serum and urine of volunteers. AB - 32 volunteers, none of whom showed any symptoms for kidney, liver or pancreas disease, were given by infusion 500 ml of various type of hydroxyethyl starch (HES) at a concentration of 6% (450/0.7, 450/0.5, 450/0.3, 300/0.4) as well as of 10% (200/0.7, 200/0.5, 200/0.3, 200/0.1) over a period of 30 min. After infusion both the Mw and the Mn diminished. The rate of elimination of HES from serum entirely depended on molar substitution and not on Mw. The quotient Mw/Mn decreased considerably over the entire test period. The lower molecular weight limit in serum remained relatively the same at 60,000 Daltons. Maximum molecular weight limit of urine, too, was 60,000 Daltons. PMID- 2581593 TI - [Potential ratios among blood levels of various blood proteins in the cord blood of healthy newborn infants]. AB - The authors have studied the correlations between IgA, IgG, IgM, C3c, C4, alpha 1 AGP and the total proteins, total globulins, alpha 1, alpha 2-globulins in normal newborn cord blood. The results indicate some significant correlations between C3c and C4, C3c, C4 and alpha 1-AGP, C3c, C4, alpha 1 1/2AGP and alpha 2 globulins, C4 and beta-globulins, C3c and alpha 1-AGP. The most significant finding has been inverse correlation between IgA and alpha 1, alpha 2-globulins, total globulins and total proteins. PMID- 2581594 TI - [Teratogenic and goitrogenic activity of propineb and propylenethiourea in the rat]. AB - The teratogenic and goitrogenic effects of Propineb, dithiocarbamate pesticide and Propylenthiourea (PLTU), its metabolite and degradation product have been studied. The aim of this study was to show the possible correlation between the two activities. Female Sprague-Dawley rats were treated with Propineb and PLTU starting from 6th to 16th day of pregnancy. The functional state of maternal and foetal thyroid, the toxicity of products versus dams and embryotoxic and teratogenic effects were examined. The observed goitrogenic effect may be compared to that reported in the previous studies of the authors, if considering time of sacrifice. In fact, the lesion quickly rises and as rapidly regresses when treatment is stopped. The foetal thyroid has not been affected by the product administered to the dams. PLTU showed a clear teratogenic activity at doses that did not show any maternal toxicity (45 and 90 mg/k). PMID- 2581595 TI - Histomorphometric evidence of deleterious effect of aluminum on osteoblasts. AB - Bone histomorphometry was performed in 26 hemodialyzed patients to study the relation between the dynamic parameters of bone formation and aluminum deposition. Patients were divided into two groups according to whether bone formation rate at tissue level (Svft) was above or below normal: 0.089 mu 3/mu 2 per day. The 12 patients who constituted group II, defined by a Svft less than 0.089 mu 3/mu 2 per day, had markedly decreased extent of double-labeled surfaces (m = 1.3 +/- 6.5%), and these were absent in 8 of 12 patients. Osteomalacia, defined by decreased formation with increased mean osteoid thickness (greater than 15 micron), was present in only 3 of 12 patients in group II. The 14 patients who constituted group I, defined by a Svft greater than 0.089 mu 3/mu 2 per day, had both increased total labeled surfaces and mineralization rate. Osteomalacia was present in none of the group I patients. In trabecular bone, group II patients had increased stainable aluminum deposition, compared to group I patients, whether estimated as total stainable aluminum (2.16 +/- 1.34 vs 0.17 +/- 0.28 mm/mm2) or stainable percent of trabecular surfaces (42 +/- 19 vs 4 +/- 5%). This last parameter was inversely related to osteoblastic surfaces (r = 0.49, n = 26, P less than 0.01) and total labeled surfaces (r = -0.72, n = 26, P less than 0.01). Therefore, massive aluminum deposition was not invariably associated with impaired mineralization but with decreased formation due to decreased extent of active formation surfaces. In the group I patients, moderate aluminum deposition was not associated with the mineralization arrest observed in these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581597 TI - A dental health project for 10-11 year olds. PMID- 2581596 TI - Relationships between calcium and phosphorus homeostasis, parathyroid hormone levels, bone aluminum, and bone histomorphometry in patients on maintenance hemodialysis. AB - Serum biochemistry related to calcium and phosphorus homeostasis and parathyroid function was studied together with bone histomorphometry after double-labeling with tetracycline and staining for aluminum in 17 patients without symptoms of bone disease, treated with maintenance hemodialysis for at least 6 months. A close correlation was found between the serum level of parathyroid hormone (PTH) and bone resorption surfaces and bone formation rates, both at tissue and basic multicellular unit (BMU) levels. The patients could be divided into a high turnover group with a normal mineralization process and a low turnover group with markedly defective mineralization. The second group was further characterized by lower PTH and higher fractional aluminum-stained trabecular bone surfaces. For the whole patient material, the fractional aluminum-stained surfaces related inversely to tetracycline-labeled surfaces and to bone formation rates at both BMU and tissue levels, but not to the time on dialysis or to the cumulative ingested amount of aluminum hydroxide. The data provide evidence that PTH or PTH related factors, besides activating bone remodeling, directly enhance bone formation in dialysis patients and that aluminum incorporation into bone is associated with a progressive disturbance of bone mineralization. PMID- 2581598 TI - Delayed recovery of left ventricular function after antithyroid treatment. PMID- 2581600 TI - Resistance to alkylating agents and tumour differentiation in xenografts of small cell lung cancer. AB - Small cell bronchial carcinoma (SCC) xenografts with differing sensitivity to cyclophosphamide (CY) were investigated using a variety of techniques. Two xenografts (HX78 and HX88) were relatively sensitive to CY, one xenograft (HX72) was inherently resistant to CY and a fourth xenograft (HX78Cy) was a CY induced resistant subline of HX78 and was unstable when maintained without CY exposure. Conventional light microscopy, cytology and electron microscopy examination of the xenografts revealed appearances consistent with SCC. An antikeratin antibody demonstrated the presence of keratin in the inherent and the induced resistant xenografts (and in the unstable revertant) but not in the two sensitive xenografts; the presence of keratin suggested squamous differentiation. Monolayer culture morphology of the sensitive HX78 and the unstable revertant was anchorage independent with the cells forming floating aggregates; the induced resistant subline of this xenograft (HX78Cy) showed, by contrast, flattened, angular adherent cells. Beta HCG production was detected in the monolayer culture supernatant of sensitive HX78 cells; the level of production of beta HCG was increased in the induced resistant HX78Cy cells. Karyotype and flow cytometry studies were also performed. The morphological responses of small cell lung cancer to treatment are discussed. PMID- 2581601 TI - Isolation and partial characterization of U1-U6 small RNAs from Bombyx mori. AB - We have used a variety of techniques to characterize the U-series small nuclear RNAs from the posterior silk gland of Bombyx mori. Six molecular species have been identified which correspond to the vertebrate U1-U6 RNAs by the following criteria: (a) presence of the RNAs in ribonucleoprotein particles which can be immunoprecipitated by lupus Sm antisera; (b) presence of a 2,2,7 trimethylguanosine cap, as assayed by immunoprecipitation with anti-2,2,7 trimethylguanosine IgG; (c) size, as assayed by acrylamide/urea gel electrophoresis using HeLa cell U-RNA markers; and (d) primary nucleotide sequence, as determined by chemical/enzymatic cleavage of end-labeled molecules. The high conservation of primary sequence (66-81% homology based on partial sequences) relative to the corresponding vertebrate U-RNAs has permitted unambiguous identification of each molecule. With the exception of two subspecies of U3 RNA, the U-snRNAs of Bombyx exhibit a striking conservation of secondary structure relative to the proposed structures of the U-RNAs of vertebrates. This conservation is best exemplified by several compensatory base alterations that result in the maintenance of hairpin structures. These are particularly evident in U1 and U5 RNAs. Bombyx U3 is interesting in that two subspecies (of a total of four that were sequenced) diverge considerably in sequence (and presumably in structure) relative to the U3 RNA of vertebrates. The most abundant U-RNAs in the posterior silk gland appear to be U1 and U2, while U3-U6 are present in relatively small amounts. PMID- 2581599 TI - Lung function and plasma levels of thromboxane B2, 6-ketoprostaglandin F1 alpha and beta-thromboglobulin in antigen-induced asthma before and after indomethacin pretreatment. AB - The effect of specific antigen challenge on the lung function of eight allergic asthmatic patients after placebo and indomethacin pretreatment has been investigated. Plasma levels of thromboxane B2(TxB2), metabolite of thromboxane A2, 6-keto-PGF1 alpha, metabolite of epoprostenol, (prostacyclin, PGI2) and beta thromboglobulin (beta TBG) following antigen challenge in these eight patients have also been measured after placebo and indomethacin pretreatment. Each patient underwent two antigen inhalations 1 week apart. One challenge took place after 4 days pretreatment with indomethacin capsules 25 mg four times daily, and the other took place following 4 days placebo pretreatment, one matched capsule four times daily. The order of administration was random but balanced and blind with respect to the patient. Following placebo pretreatment two patients presented with an early antigen response only, four presented with a biphasic antigen response and two presented with a delayed antigen response only. The asthmatic response for each patient was consistent on re-exposure. Indomethacin pretreatment suppressed the delayed antigen induced asthmatic response. This suppression was reproducible. There was a rise in plasma TxB2 levels on antigen challenge following placebo pretreatment but not following indomethacin pretreatment, whereas there was a rise in 6-keto-PGF1 alpha after antigen challenge following indomethacin but not placebo pretreatment. No significant change in plasma beta TBG or platelet counts from control values was observed following antigen challenge with either placebo or indomethacin pretreatment. It is suggested that the production of PGI2 and suppression of TxA2 by indomethacin pretreatment contribute to the suppression of the delayed antigen induced asthmatic response and that platelets play a minimal role in this process. PMID- 2581602 TI - Copper(I)-bleomycin: structurally unique complex that mediates oxidative DNA strand scission. AB - Copper(I)-bleomycin [Cu(I) X BLM] was characterized in detail by 13C and 1H NMR. Unequivocal chemical shift assignments for Cu(I) X BLM and Cu(I) X BLM X CO were made by two-dimensional 1H-13C correlated spectroscopy and by utilizing the observation that Cu(I) X BLM was in rapid equilibrium with Cu(I) and metal-free bleomycin, such that individual resonances in the spectra of BLM and Cu(I) X BLM could be correlated. The binding of Cu(I) by bleomycin involves the beta aminoalaninamide and pyrimidinyl moieties, and possibly the imidazole, but not N alpha of beta-hydroxyhistidine. Although no DNA strand scission by Cu(II) X BLM could be demonstrated in the absence of dithiothreitol, in the presence of this reducing agent substantial degradation of [3H]DNA was observed, as was strand scission of cccDNA. DNA degradation by Cu(I) X BLM was shown not to depend on contaminating Fe(II) and not to result in the formation of thymine propenal; the probable reason(s) for the lack of observed DNA degradation in earlier studies employing Cu(II) X BLM and dithiothreitol was (were) also identified. DNA strand scission was also noted under anaerobic conditions when Cu(II) X BLM and iodosobenzene were employed. If it is assumed that the mechanism of DNA degradation in this case is the same as that under aerobic conditions (i.e., with Cu(I) X BLM + O2 in the presence of dithiothreitol), then Cu X BLM must be capable of functioning as a monooxygenase in its degradation of DNA. PMID- 2581603 TI - Lamprey fibrinogen gamma chain: cloning, cDNA sequencing, and general characterization. AB - A cDNA library from lamprey liver was constructed in pBR322 and screened with a synthetic mixed oligonucleotide probe, the sequence of which was based on a partial amino acid sequence of the lamprey fibrinogen gamma chain determined by conventional procedures. Among the positive clones was one containing a 600-base insert that covered the carboxy-terminal third of the chain and another with a 1950-base insert that stretched more than full length. The two inserts were sequenced by the Maxam-Gilbert procedure. The DNA sequencing was corroborated by reference to the amino acid sequences of five cyanogen bromide peptides that compose the carboxy-terminal 130 amino acids, as well as to a number of tryptic peptides from elsewhere in the molecule. The clone with the smaller insert (6G) contained 594 nucleotides (not counting G and C tails), 435 of which are coding and correspond to residues 264-408 of the gamma chain. The remaining 159 nucleotides included the terminator codon followed by a noncoding segment. The larger clone (2E) coded for 408 amino acids that could be readily aligned with the 411-residue human gamma chain. A 24-residue signal peptide adjacent to the proposed amino terminal was also inferred. The amino acid sequence of the fibrinogen gamma chain has been differentially conserved during evolution, the lamprey and human sequences being more than 70% identical in certain key regions but dropping to less than 25% in other sections, including the segment thought to be a part of the "coiled coils". Overall, the resemblance amounts to 50% identity. Of the 10 cysteines found in mammalian chains, 9 are at identical positions, but the tenth, which in mammalian fibrinogens is a part of the interdimeric bridging, is absent in the lamprey. PMID- 2581604 TI - Inhibition of monoclonal antibody binding and proteolysis by light-induced phosphorylation of rhodopsin. AB - Light-induced phosphorylation of rhodopsin in bovine rod outer segment disk membranes inhibits the binding of three carboxyl-terminal-specific anti-rhodopsin antibodies and the cleavage of the carboxyl-terminal region of rhodopsin by trypsin and Staphylococcus aureus V-8 protease. Two monoclonal antibodies, rho 3A6 and rho 1C5, which previously have been shown to preferentially bind to the 8'-12' and the 9'-18' carboxyl-terminal segments of rhodopsin, respectively, are both highly sensitive to phosphorylation. When an average of one phosphate is incorporated per rhodopsin, the binding reactivity of rhodopsin for these antibodies decreases to 30% that of nonphosphorylated rhodopsin as measured in radioimmune competition assays. Reactivity of the rho 1D4 antibody whose primary binding site is localized in the 1'-8' C-terminal segment of rhodopsin is unaffected at this level of phosphorylation but decreases to 30% when three phosphates on average are incorporated per rhodopsin. Direct binding studies using 125I-labeled antibodies indicate that phosphorylation of rhodopsin decreases the maximum extent of rho 3A6 and rho 1C5 binding to rhodopsin. For rho 1D4, the maximum extent of binding is unaffected by phosphorylation, but the dissociation constant is increased by 10-fold. Phosphorylation of rhodopsin also inhibits cleavage of the 1'-9' and 1'-7' carboxyl-terminal peptides by trypsin and S. aureus V-8 protease, respectively. When an average of one phosphate per rhodopsin is incorporated, cleavage decreases to 40% that of nonphosphorylated rhodopsin as measured by high-performance liquid chromatography. Phosphorylation of rhodopsin had no effect on S. aureus cleavage of rhodopsin into the F1 (Mr 25 000) and F2 (Mr 12 000) fragments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581605 TI - Chemical synthesis of peptide fragments of the hormone-specific beta-subunit of human follicle-stimulating hormone. AB - In order to determine the specific antigenic determinants of human follicle stimulating hormone (hFSH), hFSH-beta peptides with amino acid residues 33-49 (V2), 95-118 (V3), 76-118 (V3 + 1/2 C2), 1-33 (V1 + C1), 22-33 (1/2C1), and 95 107 (V3 + 1/4C2) according to the nomenclature of Stewart and Stewart [Stewart, M., & Stewart, F. (1977) J. Mol. Biol. 116, 175] as well as additional peptides with the residues 93-107, 91-107, 89-107, 87-107, and 85-107 were chemically synthesized. The peptides were examined in radioimmunoassay systems of FSH, luteinizing hormone (LH), or human chorionic gonadotropin (hCG). V3 + 1/2C2 and V1 + C1 showed immunological activity, whereas the other peptides did not. Antibodies were raised in rabbits against these peptides and examined for specific binding with hFSH, LH, thyroid-stimulating hormone (TSH), and hCG. V3 + 1/2C2 as well as V1 + C1 produced antisera, which specifically bound hFSH, hLH, and hTSH, indicating that the amino acid sequences contained in hFSH-beta peptides V3 + 1/2C2 and V1 + C1 share common antigenic sites with hLH and hTSH. Antisera were produced in rabbits against hFSH-beta, against reduced and S aminoethylated hFSH-beta (AE-FSH-beta), and against AE-FSH-beta coupled to hemocyanin. Reduced and S-aminoethylated beta-subunit of FSH-beta coupled with hemocyanin produced antisera in rabbits that specifically bound only hFSH and not hLH, hTSH, or hCG. PMID- 2581606 TI - Delineation and conformational analysis of two synthetic peptide models of antigenic sites on rodent cytochrome c. AB - Two regions of rodent cytochrome c, one within the first four residues of the molecule, which is N-acetylated, and one at a beta bend around residue 44, are known to be immunogenic and antigenic in rabbits. Using sequential peptide synthesis, we have determined the residues required for linear synthetic peptides within these sequences to bind to antibody raised in rabbits to intact rat cytochrome c. The residues that were important in binding the N-terminal peptides were N-acetylglycine at position 1 and valine at position 3. The smallest peptide sequence around residue 44 that would bind to antibodies was Gln-Ala-Ala-Gly-Phe. A theoretical conformational analysis of these peptides showed that the amino terminal tetrapeptide adopts a wide statistical ensemble of conformational states and that the addition of residues beyond 41 and 45 in the other sequence does not appear to stabilize longer peptides in the native beta-bend conformation. Thus, the antigenicity conferred by Phe-46 and Gln-42 in this peptide is most likely due to the direct interaction of the side chains of these residues with the antibody binding site. The demonstration here that native conformation is not essential for antigenic peptides to bind to antibodies raised against the whole protein indicates that the association energy between antigen and antibody can be sufficient to induce conformation in conformationally flexible peptides. This supports the concept that anti-protein and anti-peptide antibodies may invoke conformational changes in cross-reactive protein antigens and may explain why longer peptides, which may adopt stable nonnative secondary structure, often do not bind to antibodies raised to the whole molecule. PMID- 2581607 TI - Immunochemical determination of conformational equilibria for fragments of the B beta chain of fibrinogen. AB - The conformations of the B beta chain of the intact fibrinogen molecule and of various fragments of the B beta chain of fibrinogen that contain the region that is hydrolyzed by thrombin have been compared by an immunochemical method [Sachs, D. H., Schechter, A. N., Eastlake, A., & Anfinsen, C. B. (1972) Proc. Natl. Acad. Sci. U.S.A. 69, 3790]. Anti-fibrinogen antibodies were induced in rabbits by immunization with native bovine fibrinogen. An antibody population specific for the native antigenic determinant within the B beta fragment 20-28 was isolated by immunoadsorption. This preparation was to determine the value of Kconf, the equilibrium constant for the interconversion of the nonnative and native conformations of this determinant. Values of Kconf were measured for this determinant within native fibrinogen, the disulfide knot (DSK), CNBrB beta, B beta fragment 16-28, B beta fragment 20-28, and fibrinopeptide B (FpB). 125I Labeled fibrinogen (125I-F) was used in the determination of Kconf by measuring the competition between 125I-F and the fibrinogen derivatives under study for binding to the purified antibody. For the antigenic region in F, the DSK, and CNBrB beta, the values of Kconf at 4 degrees C were infinity, (5.9 +/- 3.5) X 10( 3), and (1.2 +/- 0.7) X 10(-3), respectively. The values of Kconf for B beta fragment 16-28, B beta fragment 20-28, and FpB at 4 degrees C were less than (6.0 +/- 3.9) X 10(-7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581608 TI - Purification and characterization of the glycine receptor of pig spinal cord. AB - A large-scale purification procedure was developed to isolate the glycine receptor of pig spinal cord by affinity chromatography on aminostrychnine agarose. After an overall purification of about 10 000-fold, the glycine receptor preparations contained three major polypeptides of Mr 48 000, 58 000, and 93 000. Photoaffinity labeling with [3H]strychnine showed that the [3H]strychnine binding site is associated with the Mr 48 000 and, to a much lesser extent, the Mr 58 000 polypeptides. [3H]Strychnine binding to the purified receptor exhibited a dissociation constant KD of 13.8 nM and was inhibited by the agonists glycine, taurine, and beta-alanine. Gel filtration and sucrose gradient centrifugation gave a Stokes radius of 7.1 nm and an apparent sedimentation coefficient of 9.6 S. Peptide mapping of the [3H]strychnine-labeled Mr 48 000 polypeptides of purified pig and rat glycine receptor preparations showed that the strychnine binding region of this receptor subunit is highly conserved between these species. Also, three out of six monoclonal antibodies against the glycine receptor of rat spinal cord significantly cross-reacted with their corresponding polypeptides of the pig glycine receptor. These results show that the glycine receptor of pig spinal cord is very similar to the well-characterized rat receptor protein and can be purified in quantities sufficient for protein chemical analysis. PMID- 2581609 TI - Fluorometric analysis of transferable membrane pores. AB - When pore-forming factors insert into the hyperpolarized membranes of lipid vesicles, ion gradients are rapidly equilibrated, effecting complete depolarization. This process can be conveniently followed with a potentiometric cyanine dye. The generality of the method is demonstrated by applications to three diverse materials. The well-studied gramicidin channel is used to demonstrate that the method is sensitive down to concentrations of 10(-12)M. An extract from the shark repellent skin secretion of the Red Sea flatfish displays activity in the assay and is used to demonstrate the potential of the method to elucidate some of the characteristics of the pore, including its molecularity. That membrane-active factors can be detected and assayed in crude preparations is demonstrated with an impure extract of "amoebapore" from Entamoeba histolytica. In addition, variation of the buffer composition surrounding the vesicles can provide information about the ion selectivity of the pore under investigation. PMID- 2581610 TI - Studies on transcription of 3'-extended templates by mammalian RNA polymerase II. Parameters that affect the initiation and elongation reactions. AB - Addition of short sequences of dCMP residues to the 3'-OH end of duplex linear DNAs allows rapid and efficient transcription to be initiated at these sites by purified mammalian RNA polymerase II [Kadesch, T. R., & Chamberlin, M. J. (1982) J. Biol. Chem. 257, 5286-5295]. The use of such tailed DNA templates should allow biochemical studies on transcription elongation and termination with almost any desired DNA sequence. However, in vitro transcription with RNA polymerase II is aberrant in that the DNA template is not re-formed after transcription; rather, the DNA strands are separated, and most of the RNA product is found as a DNA-RNA hybrid. To better understand the factors that affect the process of transcription with these tailed DNA templates, we have varied a number of parameters that might be expected to play a role in the reaction. RNA polymerase II preparations from calf thymus, HeLa cells, and Drosophila all fail to displace the product RNA. However, RNA polymerase II from wheat germ gives only free RNA as a product, as does the Escherichia coli RNA polymerase. Hence, the displacement of the nascent RNA from a transcription complex seems to depend on some intrinsic property of the polymerase itself and not simply on the nature of the template. Variation of reaction conditions, or of the divalent metal ion, does not restore the renaturability of the DNA template. However, variation of the duplex 3'-terminal sequence of the template led to significant alterations. In general, GC-rich sites enhanced the displacement of the nascent RNA, while AT-rich sites enhanced formation of the DNA-RNA hybrid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581611 TI - Alternative conformers of 5S ribosomal RNA and their biological relevance. AB - Different conformational states of Escherichia coli 5S ribosomal RNA that may participate in protein biosynthesis have been either detected experimentally or predicted on the basis of phylogenetic sequence comparisons. The A conformer exists in a high-salt form (AH) that binds ribosomal proteins and assembles into the 50S subunit and in a low-salt form (AL), of uncertain biological relevance, that binds at least one ribosomal protein and differs in tertiary structure from the AH form. Experimentally, the AH form has been investigated comprehensively and the AL form partially. There is also a B conformer that exhibits an altered secondary structure and does not assemble with ribosomal proteins. For this conformer exhibits an altered secondary structure and does not assemble with ribosomal proteins. For this conformer to be functionally active, it must be both discrete and universal among 5S RNAs. Here, we examine its structure by employing single and double strand specific ribonucleases and nucleotide-specific chemical reagents. We demonstrate that the B form exhibits a secondary structure only a part of which is both universal and conformationally homogeneous, and we conclude, therefore, that the whole B form cannot participate in protein biosynthesis. We note, however, that progressive structural changes occur during the transitions AH----AL----B and provide evidence that the structural alteration during the transition AH----AL may be universal, which reinforces the view that the AL form is of biological relevance. PMID- 2581612 TI - Characterization of human S protein, an inhibitor of the membrane attack complex of complement. Demonstration of a free reactive thiol group. AB - S protein, an inhibitor to the membrane attack complex of complement, was purified from human plasma. The procedure involved barium citrate adsorption and fractionation by poly(ethylene glycol) 4000 precipitation, followed by chromatography on DEAE-Sephacel, Blue Sepharose, Sephacryl S-200, and finally anti-albumin-Sepharose. Reduced glutathione was added throughout to inhibit spontaneous formation of disulfide-linked S-protein dimers. The recovery was 7%, resulting in approximately 10 mg of pure S protein from 1 L of starting plasma. S protein is a single-chain molecule; sedimentation equilibrium ultracentrifugation yielded a molecular weight of 83 000; the s020,W value was estimated to be 4.0 S. The purified protein contained a free, reactive thiol group causing spontaneous formation of disulfide-linked S-protein dimers. Alkylated and nonalkylated S proteins were equally active in inhibiting C9 polymerization, catalyzed by the C5b-8 complex. In parallel with the inhibition of C9 polymerization, nonalkylated S protein catalyzed the formation of disulfide-linked C9 dimers, presumably through disulfide interchanges. PMID- 2581613 TI - Dependence of cytoplasmic calcium transients on the membrane potential in isolated nerve endings of the guinea pig. AB - The relation of changes in internal, free Ca2+, measured with arsenazo III, to the membrane potential, measured with the cyanine dye di-S-C2(5) or 86Rb+ distribution ratio, was studied in isolated guinea pig cortical nerve endings. Depolarization of the plasma membrane with veratridine or gramicidin as well as addition of ionophore A23187 led to an increase in cytosolic Ca2+. Only the response to veratridine was inhibited by tetrodotoxin. The dependence of the depolarization-induced increase in intraterminal, free Ca2+ on the membrane potential between about -50 to 0 mV was sigmoidal. A maximal increase in cytosolic Ca2+ was reached when the membrane potential was depolarized from the resting level, about -64 mV, to about -40 mV. These results show that in isolated nerve endings the activation of voltage-sensitive Ca2+ channels concomitantly leads to an increase in cytosolic, free Ca2+. Comparison of the results of the present study with the previous electrophysiological observations indicate that Ca2+ channels in synaptosomes, presynaptic nerve terminals of the squid giant synapse and cardiac cells have essentially similar voltage dependency. PMID- 2581614 TI - Lead-induced activation and inhibition of potassium-selective channels in the human red blood cell. AB - The selective increase of net K+ permeability in human red cells brought about by either Ca2+ or lead was studied using a light scattering technique to measure net K+ fluxes in cell suspensions and the patch-clamp technique to study K+ transport in individual K+-selective channels of the red cell membrane. Using ultrapure solutions it was demonstrated that the effect of lead is neither the indirect consequence of a lead-induced increase of the accessibility of the receptor sites of the K+-selective channels to traces of Ca2+ that are present as contamination in analytical grade reagents nor to the release of Ca2+ from intracellular Ca2+ stores. It is further shown that in cell-free membrane patches low concentrations of lead (10 microM) in Suprapur solutions evoke the same single-channel events as added Ca2+ and that this activity can be inhibited by high concentrations of lead (100 microM), similar to the net KCl efflux measured by means of the light scattering technique. It is concluded, therefore, that both Ca2+ and lead independently activate the same K+-selective channels in the red cell membrane. PMID- 2581615 TI - The Ca2+-sensitive K+-conductance of the human red cell membrane is strongly dependent on cellular pH. AB - The conductance of the Ca2+-sensitive K+-channels in human red cell membranes has been determined as a function of the intracellular pH. A sudden increase in the intracellular concentration of ionized calcium was established by addition of ionophore A23187 to a suspension of cells in buffer-free, Ca2+-containing salt solution. At the various cellular pH-values cellular concentrations of ionized Ca, saturating with respect to activation of the Ca2+-sensitive K+-conductance, were obtained by the use of varied concentrations of extracellular Ca2+ and added ionophore A23187. Changes in membrane potential was monitored as CCCP-mediated changes in extracellular pH. Initial net effluxes of K+, cellular K+ contents and the K+ Nernst equilibrium potentials were calculated from flame photometric measurements. Cellular Ca-contents were determined by aid of 45Ca. With cellular Ca2+ at the saturating level with respect to activation of the K+-channel the K+ conductance calculated from these data was independent of extracellular pH and a steep function of cellular pH with a half maximal conductance of 31 microSeconds/cm2 at a cellular pH of 6.1. The K+-conductance is not a simple function of cellular pH (pHc). From pHc = 6.5 and down to pHc = 6.0 a Hill coefficient of 2.5 was found, indicating cooperativity between at least two sites regulating the conductance. Below pHc = 6.0 an extremely high Hill-coefficient of 11 was found, probably indicating that the additional titration of the channel protein leads to an increased cooperativity. The importance, as a physiological regulatory mechanism, of a K+-conductance increasing from zero to maximal conductance within less than one unit of pH, is discussed. PMID- 2581616 TI - Expression of srnB gene of F plasmid by altered RNA polymerase in Escherichia coli. AB - Degradation of otherwise stable rRNA and tRNA takes place in the presence of rifampin, dependent on the F plasmid srnB gene. We have reported that a protein newly synthesized in the presence of rifampin might be a product of the srnB gene required for stable RNA degradation (Ito, R. and Ohnishi, Y. (1983) Biochim. Biophys. Acta 739, 27-34). Here we have further studied the mechanism of srnB expression. Among eighteen mutants with altered RNA polymerase, two (TJ2470 (rpoC4) and TJ302 (rpoC56)) showed RNA degradation at high temperature (42 degrees C) when the srnB gene was present. Labeling proteins at 42 degrees C in strain TJ2470 indicated that a protein of molecular weight 12 000 was a product of the srnB gene, and that expression of the srnB gene provoked RNA degradation. Using plasmid pTK4, in which the srnB gene is inserted downstream of the promoter of lacZ, lac promoter-dependent expression of the srnB gene, with production of the putative protein product, also induced RNA degradation at 42 degrees C, with no requirement for added rifampin or altered RNA polymerase. RNA degradation in these conditions was quite similar to that in the case of the addition of rifampin; e.g., it showed some responses to Mg2+, temperature and RNAase I content of the cells. Expression of the srnB gene dependent on lac promoter was also observed in minicells. Thus, it is inferred that the srnB gene is probably repressed under normal conditions with its own promoter; its expression initiates RNA turnover. PMID- 2581617 TI - Specific incorporation of 5-fluorocytidine into Escherichia coli RNA. AB - RNAs isolated from Escherichia coli B grown in the presence of 5-fluorouracil have high levels of the analog replacing uridine and uridine-derived modified nucleosides. Cytidine has also been shown to be replaced in these RNAs by 5 fluorocytidine, a metabolic product of 5-fluorouracil, but to a considerably lesser extent. When 5-fluorocytidine is added to cultured of E. coli B little 5 fluorocytidine (0.20 mol%) is incorporated into cellular RNAs because of the active cytosine/cytidine deaminase activities. Addition of the cytidine deaminase inhibitor tetrahydrouridine (70 micrograms/ml) increases 5-fluorocytidine incorporation to about 3 mol% in tRNAs, but does not eliminate 5-fluorouridine incorporation. E. coli mutants lacking cytosine/cytidine deaminase activities are able to more than double the extent of 5-fluorocytidine incorporation into their transfer and ribosomal RNAs, replacing cytidine with no detectable 5 fluorouridine incorporation. Levels of 5-methyluridine, pseudouridine and dihydrouridine in tRNAs are not affected. These fluorocytidine-containing tRNAs show amino acid-accepting activities similar to control tRNAs. Fluorocytidine was found to be quite susceptible to deamination under alkaline conditions. Its conversion to primarily 5-fluorouridine follows pseudo-first-order reaction kinetics with a half-life of 10 h in 0.3 M KOH at 37 degrees C. This instability in alkali probably explains why 5-fluorocytidine was not found earlier in RNAs isolated from cells treated with 5-fluorouridine, since most early RNA hydrolyses were carried out in alkali. It may also explain the mild mutagenic properties observed in some systems following 5-fluorouridine treatment. Initial 19F-NMR measurements in fluorocytidine-containing tRNAs indicate that this modified tRNA may be useful in future structural studies of tRNAs and in probing tRNA-protein complexes. PMID- 2581618 TI - Nuclear matrix-associated DNA methylase. AB - Previous procedures for the extraction of DNA methylase (EC 2.1.1.37) from nuclei of mouse ascites cells have involved the use of buffers containing 0.2M NaCl. Whilst such 'soluble' methylase accounts for the bulk (70-80%) of DNA methylase activity a further portion of activity is detectable in a 'bound' form firmly associated with 2 M NaCl-resistant nuclear matrix-like structures. This association, which in part requires continuing DNA replication and protein synthesis, can, however, be disrupted in vitro with high concentrations of ammonium sulphate, and the enzymic properties of the 'bound' form of DNA methylase are similar to those described for the 'soluble' form. PMID- 2581619 TI - Heterogeneity in the globin chain composition of a human minor fetal hemoglobin component. AB - The first hemoglobin found to contain an acetyl blocking group was the minor human fetal hemoglobin, Hb FI, present as 10-15% of the total fetal hemoglobin in umbilical cord blood red cells. Acetylation occurs at the amino-terminal glycine of the gamma-globin chain. Assays for the acetyl group by two different methods gave values less than the 2 per tetramer expected for a fully acetylated hemoglobin. We have purified acetylated fetal hemoglobin FIc to homogeneity. The globin chain composition of Hb FIc has been examined by both globin chain separation on CM-cellulose and by tryptic peptide mapping by HPLC. The identities of the gamma globin chains and of the gamma T-1 peptides were confirmed by amino acid analysis. Globin chain separation profiles showed the presence of 22.3 +/- 7.0% of gamma 0 globin (of the total gamma globin) in Hb FIc. Accordingly, the tryptic peptide maps of Hb FIc tetramers also showed the presence of a similar amount of gamma 0T-1 peptide. The gamma 0T-1 peptide was not present in the maps of isolated gamma Ic globin. It is evident that column purified Hb FIc contains a certain percentage of non-acetylated gamma-globin chains, thus indicating a hybrid globin chain composition for this minor fetal hemoglobin component. PMID- 2581620 TI - Effect of FS (alpha 2 gamma beta s) hybrid hemoglobin on Hb S nucleation and aggregation. AB - Asymmetrical cross-linked FS (alpha 2 gamma beta s) hybrid hemoglobin (Hb FS fumarate) was prepared by reacting mixtures of hemoglobins F and S with double headed aspirin, bis(3,5-dibromosalicyl) fumarate. When the molar ratio of hemoglobin to the cross-linking agent was 1 to 2 in a 1:1 FS mixture, the relative ratio of the products, cross-linked hemoglobins F (Hb F-fumarate), FS (HB FS-fumarate), and S (Hb S-fumarate), was 1.0:2.6:2.0, in contrast to a 1:2:1 ratio of cross-linked hemoglobins A, AS, and S in a 1:1 AS mixture. These results suggest that the fumaryl group reacts differently with Hb F, Hb FS and Hb S, and that the difference could be attributed to the difference in the structure in the vicinity of the EF6 Lys of non alpha-chains. The oxygen-binding properties of Hb F-fumarate, Hb FS-fumarate, and Hb S-fumarate were similar, except that the n value of Hb F-fumarate was slightly lower than n-values of Hb S-fumarate and Hb FS-fumarate. Kinetic studies on aggregation showed that the addition of Hb FS fumarate to unmodified Hb S did not affect the delay time prior to aggregation, but did increase the total turbidity. Electrophoretic and densitometric scanning analysis of the aggregate phase of this mixture showed the fraction of Hb FS fumarate to be 19%. Hb F-fumarate's effect on the delay time is concentration dependent; the greater the concentration of Hb F-fumarate, the longer the delay time. The turbidity after aggregation of the mixture of Hb S and Hb F-fumarate was much less than that of Hb S and Hb FS-fumarate. However, the fraction of Hb F fumarate in the aggregate phase was 19%, which is similar to that of Hb FS fumarate. These data suggest that Hb F and FS hybrid hemoglobin cannot participate in nuclei formation, but can participate in aggregation after sufficient amounts of nuclei are formed from Hb S, and that increased levels of Hb F do not have an inhibitory effect on the formation of nuclei but on the growth of aggregates. PMID- 2581621 TI - Purification and immunological characterisation of two calcium-activated neutral proteinases from rabbit skeletal muscle. AB - Two Ca2+-activated neutral proteinases have been prepared to a high degree of purity from rabbit skeletal muscle. One, calpain I, is optimally activated by 100 microM Ca2+ and the other, calpain II, by 1 to 2 mM Ca2+. Both enzymes have two subunits of molecular weight 80 000 and 28 000. Antibodies have been raised against the native forms of both enzyme. It was found that the antibody to native calpain I reacted only with calpain I and not with calpain II, and similarly the antibody to native calpain II reacted only to calpain II. This suggested that the epitopes in the two enzymes are located in regions that are structurally different. However, immunoblotting of the denatured calpains after SDS polyacrylamide-gel electrophoresis revealed cross-reaction between the two subunits for both enzymes. Therefore, although the denatured enzymes have common antigenic sites it would appear that these are not exposed equally in the native proteins. PMID- 2581622 TI - The activation of the sodium pump in pig red blood cells by internal and external cations. AB - A study has been made with pig red blood cells of the activation of the sodium pump by internal and external cations. Cell Na and K concentrations were altered using a PCMBS cation loading procedure. The procedure was characterised for resultant ionic conditions, maintenance of ATP levels and fragility. The activation of the sodium pump by external K was measured in cells suspended in choline (Na-free) solutions. External Cs was used as a substitute for K and elicited lower rates of pump activity. Both the Vmax and apparent Km for 42K influx and 134Cs influx increased as internal Na concentration was raised (within the non-saturating range). Vmax/apparent Km ratios for cation influx were constant. Raising external Cs concentration exerted a similar influence on pump activation by internal Na: both the maximum pump velocity and the apparent Na site dissociation constant (K'Na) increased. The results provide evidence for a transmembrane connection between cation binding sites on opposite faces of the membrane and are consistent with a consecutive model for the sodium pump in pig red blood cells. PMID- 2581623 TI - Suppression of 1,25-dihydroxy-vitamin D3-dependent calcium transport by protein synthesis inhibitors and changes in phospholipids in skeletal muscle. AB - The effects of protein synthesis inhibitors on 1,25-dihydroxy-vitamin D3 dependent Ca uptake were evaluated in vitamin D-deficient chick soleus muscle and chick embryo myoblast cultures in order to obtain information about the mechanism by which 1,25-dihydroxy-vitamin D3 affects muscle calcium transport. Puromycin (50 microM, 5 h) and cycloheximide (50 microM, 24 h) blocked the increase in Ca uptake induced by the metabolite in soleus muscle and myoblasts, respectively. Actinomycin D (1.6 microM, 12 h) was also effective in inhibiting 1,25-dihydroxy vitamin D3-dependent Ca uptake in myoblasts. These results suggest that the effects of 1,25-dihydroxy-vitamin D3 on muscle Ca uptake are mediated by de novo protein and RNA synthesis. In addition, it could be observed that myoblasts treated with 1,25-dihydroxy-vitamin D3 had increased lipid phosphorus, phosphatidylcholine and sphingomyelin contents. These changes may be the consequence of the nuclear action of the sterol or, alternatively, represent an independent effect as has been proposed for intestine. PMID- 2581624 TI - HeLa cells have histamine H1-receptors which mediate activation of the K+ conductance. AB - HeLa cells responded to exogenous histamine with a transient hyperpolarization due to increased membrane conductance to K+. After successive applications of histamine, the cell membrane became virtually unresponsive (desensitized). The responses were blocked by pyrilamine but not by cimetidine. Thus, it appears that HeLa cells have H1-receptors which mediate an increase in the K+ conductance. PMID- 2581625 TI - [The human major histocompatibility complex or HLA complex]. PMID- 2581627 TI - [Modification by azocombination of the catalytic properties of ribonucleases]. AB - Using pancreatic RNAase and RNAase from Act. rimosus as models, the effect of modification by azocombination on the catalytic properties of enzymes were studied. It was shown that RNAases binding to soluble dextran did not cause any significant changes in their major catalytic properties, when polymeric RNA was used as a substrate. At the same time, the physico-chemical properties of the modified enzymes may result in changes in the catalytic properties in a reaction with low molecular weight substrates. Evidence for this observation can be obtained from the increase in the synthetic activity of modified pancreatic RNAase as compared to the hydrolase activity in the dinucleotide synthesis reaction. PMID- 2581628 TI - [Comparative study of gangliosides from murine B- and T-lymphomas]. AB - Gangliosides from murine B-lymphomas (MOPC 21 and MOPC 406) and T-lymphoma EL-4 were studied by thin-layer chromatography, immunoprecipitation with specific antisera to gangliosides and by treatment with neuraminidase. It was found that the gangliosides of all three lymphomas differ in their interaction with antisera and neuraminidase although they are similar in their chromatographic behaviour. PMID- 2581626 TI - Diversity in the immune system: "preconceived ideas" or ideas preconceived? AB - Two concepts of the evolution and regulation of expression of the combining site repertoire of the immune system, are compared. One view is based on the Associative Recognition Theory as formulated by the author and the other is based on the Idiotype Network Idea as conceived by Jerne. The two concepts are analyzed from the point of view of their logic, internal consistency and factual support. PMID- 2581629 TI - Induction of cell-mediated cytotoxic immunity to sperm-specific lactate dehydrogenase-C4 in SJL/J female mice. AB - SJL/J female mice were tested for a cell-mediated cytotoxic response to sperm specific lactate dehydrogenase C4 (LDH-C4). We demonstrated this response with a 51chromium release assay. Mouse LDH-C4 was coupled to EL-4 tumor cells. These cells were then labeled with 51Cr and mixed with splenocytes from LDH-C4-immune and -nonimmune mice. Specific lysis of the tumor cells by splenocytes from LDH-C4 immune mice was detected at 7 days and 14 days following a single footpad immunization. Since LDH-C4 is present on the surface of sperm, these results support the suggestion that cytotoxic removal of sperm from the female reproductive tract is one of the mechanisms whereby fertility is reduced following immunization with this enzyme. PMID- 2581630 TI - Dependence of purine 8C-H exchange on nucleic acid conformation and base-pairing geometry: a dynamic probe of DNA and RNA secondary structures. PMID- 2581631 TI - Sequence and conformational effects on imino proton exchange in A.T- and A.U containing DNA and RNA duplexes. PMID- 2581632 TI - Chronic myelogenous leukemia: recent advances. PMID- 2581634 TI - Monoclonal antibodies against plasma protease inhibitors: production and characterization of 15 monoclonal antibodies against human antithrombin III. Relation between antigenic determinants and functional sites of antithrombin III. AB - Fifteen hybridomas secreting monoclonal antibodies against human antithrombin III, originating from two mouse strains, have been produced by the cell fusion technique. Eight monoclonal antibodies belong to the class IgG1, five to the class IgG2a, and two to the class IgG2b. All light chains belong to the kappa group. No cross-reaction of the monoclonal antibodies have been observed with a crude preparation of albumin nor with alpha 1-antitrypsin and alpha 2 antiplasmin. Five of these monoclonal antibodies exhibit a relatively high avidity for antithrombin III. Inhibition experiments showed that the 15 monoclonal antibodies define seven more or less independent antigenic regions on the antithrombin III molecule. Examination of the effects of these antibodies on the inhibitory capacity of antithrombin III toward thrombin activity, either in the presence or in the absence of heparin, showed that several monoclonal antibodies inhibit the antithrombin III activity and allowed to relate some of the antigenic determinants to functional sites on the antithrombin III molecule. PMID- 2581633 TI - Studies on the structure of bovine factor V by scanning transmission electron microscopy. AB - We studied purified bovine factor V (mol wt 330,000) by scanning transmission electron microscopy (STEM) of freeze-dried unstained or negatively contrasted preparations. Freeze-dried molecules revealed discrete shapes ranging from roughly spheroidal (100 to 120 nm) to oblong (140 to 200 nm in length X 50 to 100 nm in width). Oblong shapes could often be resolved into two or three distinct domains, ranging from 60 to 100 nm in diameter. A "satellite" nodular structure (30 to 50 nm in diameter) connected to the main molecule by a thin stalk (approximately 10 nm wide) up to 80 nm in length was occasionally seen. Glutaraldehyde-treated preparations yielded the same shapes as were seen in unfixed preparations but revealed better definition of submolecular features and "satellite" nodules. STEM mass analysis confirmed that each of the different shapes represented a monomolecular form of factor V. Negatively stained images revealed objects having the same general shapes as freeze-dried molecules, although greater detail was evident. Some images suggested that molecules consist of five or more discrete parts. Taken together, these observations indicate that factor V molecules are multidomainal, flexible structures that tend to have an irregular oblong shape with an axial ratio between 3:2 and 2:1. PMID- 2581635 TI - Preferentially expressed genes in chronic myelogenous leukemia. AB - The predominant circulating cells in chronic myelogenous leukemia (CML) morphologically resemble normal myeloid precursors; however, certain characteristics indicate the two are not identical. Approximately 88% of the patients with clinically typical CML present with a cytogenetic abnormality known as the Philadelphia chromosome (Ph1). Additionally, the leukocyte alkaline phosphatase (LAP) value is decreased in CML. To investigate if there are selected genes expressed in the CML cell population, poly(A+)RNA from a chronic-phase, Ph1 positive CML patient was used for construction of a complementary DNA (cDNA) library. Recombinant clones representing moderately to abundantly transcribed sequences were selected by annealing [32P]-cDNA transcribed from homologous RNA to the library sequences and assessing radioactivity in the hybrids. From an initial 729 colonies, 417 (57.2%) displayed a hybridization signal more intense than controls, indicating these recombinant plasmids contained sequences homologous to moderately or highly expressed RNAs from this particular patient. Screening of the 417 clones--utilizing 32P-cDNAs derived from normal human placenta, an acute myelomonocytic leukemia (AMML), and two other CML samples--was used to select clones likely to represent sequences preferentially expressed in CML. Sixteen recombinants were initially selected that repeatedly failed to display hybridization with the placenta and AMML-derived probes. Further analysis of eight of these clones indicated that six contain sequences preferentially expressed in CML. One clone, C-A3, has been studied with 63 different RNA samples. This sequence is found to be highly expressed in peripheral blood cells from the chronic phase of both Ph1-positive and Ph1-negative CML as well as in a Ph1-positive acute myelogenous leukemia (AML). Expression is reduced in lymphoblastic crisis of CML (L BC-CML) and essentially absent in myeloblastic crisis of CML (M BC-CML). While preliminary, the results suggest that this probe may be useful as an aid in diagnosing Ph1-negative CML and in distinguishing M BC CML from L BC-CML and Ph1-positive AML. PMID- 2581636 TI - Surface membrane expression by human blood leukocytes and platelets of decay accelerating factor, a regulatory protein of the complement system. AB - The decay-accelerating factor (DAF), an integral membrane protein of approximately 75,000 mol wt that regulates the stability of the C3 convertases of the classical and alternative complement pathways, was initially isolated from normal erythrocyte stroma and used to prepare a polyclonal antiserum. Previously, anti-DAF antiserum has been used to immunoprecipitate DAF from surface-labeled normal erythrocytes and to document the deficiency of DAF on the surface of erythrocytes from patients with paroxysmal nocturnal hemoglobinuria, a condition in which erythrocytes express abnormal sensitivity to complement-mediated lysis. DAF has now been demonstrated by cytofluorography with anti-DAF F(ab')2 and fluoresceinated second antibody to be present on the surface of resting polymorphonuclear leukocytes (PMN), monocytes, lymphocytes, and platelets. Populations of PMN, monocytes, and platelets each exhibited a unimodal distribution of fluorescent staining, reflecting uniform cellular expression of DAF antigen, while the lymphocyte population had a skewed pattern of staining, indicating the heterogeneous expression of DAF antigen. For platelets, the shift in mean fluorescence channel observed with cytofluorographic analysis was minimal, but the presence of surface DAF on platelets was demonstrated by specific and saturable anti-DAF F(ab')2 binding. The DAF antigen, analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of dithiothreitol-reduced anti-DAF immunoprecipitates prepared from surface-labeled, isolated populations of cells, presented a single polypeptide chain of approximately 84,000 mol wt for PMN and 75,000 to 80,000 mol wt for monocytes, T and B lymphocytes, and platelets. Thus, the complement regulatory protein, DAF, is expressed on the surface of all major types of circulating blood cells from normal donors. PMID- 2581637 TI - Structurally diverse molecular deletions in the beta-globin gene cluster exhibit an identical phenotype on interaction with the beta S-gene. AB - We have characterized a new deletion that increases hemoglobin F synthesis in an American black woman who is doubly heterozygous for this mutation and the beta S gene. The 5' endpoint is 2.4 +/- 0.1 kilobases (kb) upstream from the delta globin gene, and the 3' endpoint is 0.2 +/- 0.1 kb downstream from the beta globin gene; the deletion is 12 kb long. Both members of the Alu moderately repetitive DNA sequence family, normally present upstream from the delta-globin gene, are preserved. The patient is asymptomatic with a mild anemia and 24.8% HbF. The patient's husband and daughter have a similar clinical syndrome, with HbF levels of 22.4% and 25.4%, respectively. Both husband and daughter are doubly heterozygous for the beta S-gene and the Ghana type of hereditary persistence of fetal hemoglobin (HPFH) deletion (HPFH-2). The 5' end of this deletion is in the psi beta-gene, and its total length is more than 70 kb. All three members of the family have normocytic red cells, of which 95% or more are F cells as detected by immunofluorescence. Previous studies have shown that culture of the erythroid progenitors (BFU-E) from both types of these compound heterozygotes in the presence of fetal sheep serum, rich in "switching factor," resulted in complete suppression of HbF synthesis. Although the newly described deletion resembles the Sicilian type of delta beta-thalassemia by its size and preservation of the Alu sequences, the clinical and biological phenotype produced by its interaction with the beta S-gene is very similar to that of the HPFH-type deletion. PMID- 2581638 TI - Quantitation of protein 3 content of circulating erythrocytes at the single-cell level. AB - The density and size of human erythrocytes has been roughly correlated with cell age, with the denser and smaller cells being older. Observations of this type have led to a hypothesis that the membranes of circulating erythrocytes are dynamic with respect to composition and that material is lost from the membrane during cell maturation and circulation. In this study, flow cytofluorimetry was used to investigate the distribution of the human erythrocyte anion transport protein (protein 3) in heterogeneous samples of circulating red cells. We verified that protein 3 can be specifically and quantitatively labeled in intact human erythrocytes with eosin-5-maleimide, a luminescent probe. Individual cells were accordingly analyzed for size by forward light scattering and for protein 3 content by quantitation of eosin fluorescence. Initial results indicated that the smallest erythrocytes had a protein 3 content equal to that of the largest circulating erythrocytes. This result was independently verified by light scatter activated cell sorting; direct measurement of cell diameters by microscopy verified that the cell sizes of erythrocytes showing the 10% greatest and 10% smallest light-scattering signal were indeed distinct. Independent analysis of the size-sorted erythrocytes for protein 3 content was accomplished by gel electrophoresis of stroma from 150,000 large and small erythrocytes. Quantitative scanning densitometry of silver-stained gels of prepared stroma showed that protein 3 content of each set of fractionated cells was equal and did not vary as a function of cell size. Taken in combination with the reported correlation between increasing red blood cell age and decreasing cell size, these results indicate that any loss of membranous material during the cell aging process is not random. PMID- 2581639 TI - 5q- chromosome in acute leukemia with lymphoid morphology and expression of myeloid membrane determinants. AB - We present three patients, two children and one adult, with an unusual type of acute leukemia. Whereas the blast cells showed lymphoid morphology with correlating cytochemical staining, immunological phenotyping exhibited a pure myeloid in one patient and a biphenotypic membrane marker profile in the other two patients. Cytogenetic studies revealed a 5q- chromosome as a common marker and additional individual changes. Two of the patients who were treated according to acute lymphoblastic leukemia (ALL) therapy protocols died without remission five and four weeks after diagnosis, respectively. Despite relapsing several times, another patient survived for over eight years. These three patients seem to represent one new subgroup of leukemias that can only be distinguished from typical ALL by both determination of cell surface markers and cytogenetic analysis. PMID- 2581640 TI - Identification of human megakaryocyte coagulation factor V. AB - Specific monoclonal and polyclonal antibody reagents and a double antigen indirect immunofluorescence microscopy technique were used to visualize coagulation factor V in human bone marrow. Marrow aspirates were smeared directly on glass slides, or washed and cytospun onto glass slides, or processed and plated into a plasma/methylcellulose cell culture system. Morphologically identifiable colonies of megakaryocytes, erythrocytes, granulocytes, or monocytes/macrophages were removed from 14- to 18-day marrow culture dishes by micropipette and streaked onto glass slides. Smears of marrow cell preparations were air-dried, fixed, washed, and incubated sequentially with primary IgG antibody reagents and with secondary anti-IgG antibody reagents conjugated with either fluorescein or rhodamine. Preparations were examined and photographed through a microscope suitably equipped for two-color fluorescence and phase contrast analysis. Cells of megakaryocytic lineage were identified by their immunofluorescent reactivity with murine monoclonal antibody HP1-1D, specific for human platelet plasma membrane glycoprotein IIb/IIIa (GP IIb/IIIa), or by their immunofluorescent reactivity with monoclonal or polyclonal antibodies specific for von Willebrand factor (vWF) or for platelet factor 4 (PF4). Coagulation factor V in bone marrow was detected by simultaneous immunofluorescent staining with polyclonal burro anti-human factor V antibody or with a panel of murine monoclonal anti-human factor V antibodies. The double antigen immunofluorescence staining technique, incorporating appropriate controls, revealed that coagulation factor V was principally located in marrow cells simultaneously identified as megakaryocytes by antibodies to GP IIb/IIIa, vWF, or PF4. The specific immunofluorescence of factor V in megakaryocytes and platelets was eliminated when excess purified factor V antigen was preincubated with anti-factor V antibody. Our observations establish the presence of human megakaryocyte coagulation factor V, confirm the presence of human platelet factor V, and indicate that human megakaryocyte/platelet coagulation factor V is a lineage associated protein. PMID- 2581641 TI - Neonatal alloimmune thrombocytopenic purpura and congenital porencephaly in two siblings associated with a "new" maternal antiplatelet antibody. AB - We report a brother and sister, both of whom have porencephaly, hydrocephalus, optic atrophy, severe mental retardation, and spastic quadriplegia. In the younger child, abnormal intracranial structure was demonstrated by sonography at 32 weeks' gestation and was suspected earlier. Both children had transient severe thrombocytopenia as newborns. The mother is healthy and has never had purpura or other bleeding symptoms. However, her serum was found to react strongly with platelets from the father and from both children. The antibody in the mother's serum is platelet-specific but does not appear to be directed against any of the known antigens associated with neonatal alloimmune thrombocytopenic purpura (NATP) in other families, including PlA1, PlE2, or Baka. Although the mother's serum reacts with platelets from all 47 unrelated normal donors tested and from both the mothers and the fathers of 17 other children with suspected NATP, it does not react with her own platelets or with platelets from a patient with Glanzmann's thrombasthenia. These observations suggest that the serum from this woman identifies a previously undescribed high-frequency platelet-specific alloantigen and that sensitization to this determinant caused severe immune thrombocytopenia in both her children. It is likely that this led to intracranial hemorrhage in utero in these cases. PMID- 2581642 TI - Microtubule reassembly in surface-activated platelets. AB - It is generally accepted that a circumferential microtubule supports the discoid shape of resting platelets. The fate of the many-coiled polymer following platelet activation, however, has been a subject of considerable debate. Morphological investigations have suggested that the circumferential coils are constricted into tight rings around centrally concentrated organelles during platelet shape change. Biochemical studies employing colchicine-binding assays, on the other hand, have indicated that the bundle of microtubules dissolves almost completely within seconds after activation and reassembles in a new location one to four minutes later. The present study has accepted the latter hypothesis in order to examine the second part of the disassembly-reassembly theory proposed in biochemical studies. Platelets exposed to low temperatures sufficient to remove all microtubules were placed on glass slides and microscope grids to cause surface activation during rewarming. The combined stimuli of rewarming and surface activation might have been expected to cause more rapid assembly than warming alone or activation alone. This was not the case. Reassembly of microtubules during rewarming and simultaneous surface activation was not accelerated. In contrast to the constriction of microtubule rings observed during activation in control platelets, the diameters of coils that developed in chilled platelets one to two hours after rewarming and surface activation were twice those of control cells. PMID- 2581643 TI - Effect of the cytotoxin of Clostridium difficile on cultured hepatoma cells. AB - Clostridium difficile is the major etiologic agent of human pseudomembranous colitis. It produces two toxins: an enterotoxin and a cytotoxin. In cultured hepatoma cells, at very low doses, the cytotoxin inhibits the incorporation of precursors into biological macromolecules. Protein synthesis is more affected than RNA and DNA synthesis. The toxin also induces severe alterations of the cell morphology consisting in damages to the cytoskeleton and to the cell shape. PMID- 2581644 TI - Relationship between growth inhibition and mitochondrial function in petite negative yeasts. I. Effects of antibiotics and dyes upon pathogenic and non pathogenic Candida species. AB - Antibiotics and dyes which preclude growth of Saccharomyces cerevisiae in media containing oxidizable carbon sources arrested the growth of Candida albicans, Candida tropicalis and Candida utilis even in glucose medium. The growth in the presence of sub-inhibitory concentrations of the various antibiotics and dyes determined a reduction in the cell survival but with no accumulation of respiratory deficient mutants. Under these culture conditions, the total respiration declined leaving a residual antimycin A-resistant--hydroxamate sensitive O2 uptake, and the amount of the respiratory cytochromes aa3 and b synthesized was reduced. SDS gel electrophoresis of soluble proteins prepared from the antibiotic-treated cells showed some bands in the MW range 92-100 K, which became faint after the cells were grown in the presence of some mitochondrial inhibitors. The ultrastructural analysis of these cells evidenced disappearance of the mitochondrial cristae and their replacement by unfolded membranes. The data obtained suggest that the petite negative trait of Candida could depend on the non-viability or on the very low viability of those cells which have lost their mitochondrial function. PMID- 2581645 TI - Bibliographic control of audiovisuals: analysis of a cataloging project using OCLC. AB - The staff of the Quillen-Dishner College of Medicine Library cataloged 702 audiovisual titles between July 1, 1982, and June 30, 1983, using the OCLC database. This paper discusses the library's audiovisual collection and describes the method and scope of a study conducted during this project, the cataloging standards and conventions adopted, the assignment and use of NLM classification, the provision of summaries for programs, and the amount of staff time expended in cataloging typical items. An analysis of the use of OCLC for this project resulted in the following findings: the rate of successful searches for audiovisual copy was 82.4%; the error rate for records used was 41.9%; modifications were required in every record used; the Library of Congress and seven member institutions provided 62.8% of the records used. It was concluded that the effort to establish bibliographic control of audiovisuals is not widespread and that expanded and improved audiovisual cataloging by the Library of Congress and the National Library of Medicine would substantially contribute to that goal. PMID- 2581646 TI - From skills lab to learning resource center: transformation through collaboration. PMID- 2581647 TI - Effects of somatostatin and a long-acting somatostatin analogue on the prevention and treatment of experimentally induced acute pancreatitis in the rat. AB - The effects of somatostatin (SRIF) and its long-acting analogue, SMS 201-995 on the prevention and treatment of acute pancreatitis were studied in rats. Acute pancreatitis was established by ligating the bile duct at the point of entry into the duodenum, thereby allowing reflux of bile into the pancreas. Administration of SRIF (4 micrograms kg-1 body wt IV followed by a 12 h infusion of 4 micrograms kg-1 body wt h-1) or SMS 201-995 (2 micrograms kg-1 body wt SC) at the time of bile duct ligation prevented the increase in the serum concentrations of amylase and lipase observed in control rats 12 h after bile duct ligation. Moreover, SRIF and SMS 201-995 administration prevented development of the histological changes consistent with acute pancreatitis observed in control animals. These results suggest that SRIF or SMS 201-995 may be of value in preventing acute pancreatitis following ERCP or after surgery on the pancreas. In rats with established pancreatitis, SRIF (IV bolus of 4 micrograms kg-1 body wt followed by a 24 h continuous infusion of 4 micrograms kg-1 body wt h-1) or SMS 201-995 (2 micrograms kg-1 body wt SC followed by a similar dose 12 h later): (1) significantly improved survival; (2) produced histological changes in the pancreas consistent with organization and healing; (3) prevented the accumulation of ascitic fluid; (4) reduced the serum levels of amylase and lipase. These results suggest that SRIF and SMS 201-995 may prove valuable in the treatment of established acute pancreatitis in man. PMID- 2581648 TI - Nerve growth factor counteracts the neurophysiological and neurochemical effects of chronic sciatic nerve section. AB - The sciatic nerve was sectioned unilaterally in rats and nerve growth factor (NGF) applied locally to the nerve stump for the following 10-14 days using an indwelling osmotic pump. The aim of the experiment was to test whether NGF had any effect on the previously reported neurophysiological and neurochemical events that occur central to a peripheral nerve lesion. The method of application allowed the sciatic nerve on the other side to be used as a control. Primary afferent depolarization fell, as expected, to 13% of its control value after chronic nerve section but if NGF was administered it fell to only 43.5% of control. Chronic nerve section is also known to result in expansion of the receptive fields of deafferented dorsal horn cells. NGF treatment reduced the number of such large receptive fields by 50%. The normal depletion of fluoride resistant acid phosphatase from the cut nerve terminals in the dorsal horn did not occur following NGF treatment. Radioimmunoassay of substance P revealed that the 30% reduction in dorsal horn levels that follows chronic sciatic nerve section did not occur when NGF was applied and that the accompanying 60% decrease in dorsal root ganglion levels was changed to a 64% increase by NGF. The results show that chronic NGF treatment of a cut sciatic nerve does partially reverse the central changes that normally follow deafferentation. PMID- 2581649 TI - The substance P receptor subtype modulating catecholamine release from adrenal chromaffin cells. AB - Substance P (SP) has two distinct actions on catecholamine (CA) release from cultured bovine adrenal chromaffin cells: SP inhibits acetylcholine (ACh)- or nicotine-induced [3H]norepinephrine ([3H]NE) release; and SP protects against desensitization of ACh- or nicotine-induced [3H]NE release. In order to characterize the SP receptor subtypes modulating these two actions, we have tested several SP-related tachykinins and SP analogues for their ability to act as agonists of SP for these actions. The naturally occurring tachykinins, physalaemin, eledoisin and kassinin, were about equipotent and all much less potent than SP in inhibiting nicotine-induced [3H]NE release. Physalaemin and eledoisin were also approximately equipotent and much less potent than SP in protecting against desensitization of nicotine-induced [3H]NE release; kassinin slightly enhanced nicotinic desensitization. These results indicate that neither a kassinin-like nor a physalaemin-like peptide are likely to modulate adrenal CA release. The 'SP-P' receptor-selective analogue, SP-methyl ester, was an agonist, equipotent with SP, for both of SP's actions on [3H]NE release. [D-Pro2,D-Trp7,9] SP, a potent antagonist of SP's actions in many SP-responsive tissues, was inactive as an antagonist of both of SP's actions on [3H]NE release from adrenal chromaffin cells; however, this analogue was a potent SP agonist in chromaffin cells. The rank order of potency of these and other SP-related peptides for inhibition of [3H]NE release was similar to their order of potency for protection against desensitization. Thus the chromaffin cell SP receptors mediating inhibition of nicotine-induced [3H]NE release appear to be very similar to those mediating protection against desensitization of nicotine-induced [3H]NE release. The results indicate that the SP receptors modulating adrenal CA release are different from either the 'SP-P' or 'SP-E' receptor subtypes; bovine adrenal chromaffin cells appear to possess a third subtype of SP receptor which shares similar characteristics with the SP receptors mediating histamine release from rat mast cells. PMID- 2581650 TI - Synthesis and fast axonal transport of proteins in the isolated Aplysia nervous system. AB - Fast axonal transport and neuronal protein synthesis was studied in the isolated nervous system of Aplysia californica. The abdominal ganglion with attached pleural-abdominal connectives (PAC) was removed and the ganglion pulse-labelled with [35S]methionine for 30 min in vitro. The axon containing connectives were ligated 24-28 mm from the ganglia and the system was perfused with chase media for 6-72 h to allow labelled rapidly transported proteins to accumulate at the ligature. One-dimensional polyacrylamide gel electrophoresis (PAGE) and fluorography was used to analyze the distribution of rapidly transported proteins along the right PAC. By 12 h, a significant accumulation of labelled proteins at the ligature was present but the build up was not complete until 48 h when almost no trailing of rapidly transported proteins was observed. Quantitation of the transport profiles of several rapidly transported proteins suggested a discontinuous release of proteins from the cell body. Analysis using two dimensional PAGE revealed 10 major groups of rapidly transported proteins. These proteins were all identified among the total complement of newly synthesized proteins in cell R2. Not all rapidly transported proteins are cleared from the cell body at the same rate. Several of the major groups were no longer present in the neuron cell body 24 h after labelling, indicating that these species are selectively exported; others were still present after 3 days, suggesting that these proteins with a longer residence time have functions in both somatic and axonal regions of the neuron. PMID- 2581651 TI - Sciatic nerve transection produces death of dorsal root ganglion cells and reversible loss of substance P in spinal cord. AB - Sciatic nerve section has been shown to reduce substance P (SP) in the dorsal horn of the spinal cord, but the mechanism which underlies the reduction is not understood. Whether SP levels subsequently recover as they do after dorsal rhizotomy has also been unknown. To test the hypothesis that transganglionic degeneration of primary afferents contributes to the reduction of SP, we have studied the changes in SP which result from section of the cat sciatic nerve and determined the extent of dorsal root ganglion (DRG) cell death. Sciatic nerve section resulted in DRG cell death, but the amount was variable and not seen in all animals. Reduction in dorsal horn and DRG SP was seen in all animals, and in the spinal cord it was followed by recovery. These sequelae resemble the changes which follow dorsal rhizotomy. After sciatic nerve section, the reduction in dorsal horn SP is smaller than after rhizotomy, the recovery more complete, and both the reduction and the recovery proceed more slowly. Evidence is presented that similar mechanisms may contribute to depletion of intraspinal SP after sciatic nerve section and after dorsal rhizotomy. The mechanisms contributing to recovery of spinal cord SP after sciatic nerve section may resemble known mechanisms of recovery that occur when the lesion is central. PMID- 2581652 TI - Cyclocytidine-induced release of nerve growth factor from mouse submandibular glands enhances regeneration of sympathetic fibers in adult mice. AB - The injection of a drug endowed with the property of stimulating alpha-adrenergic receptors, cyclocytidine (Cyclo-C), produces drastic depletion of NGF from the granular convoluted tubules (GCT) of the mouse submaxillary salivary gland and a marked NGF level increase in the bloodstream. The NGF discharged from the gland gains access to the blood. Histological studies, immunohistochemistry, in vitro biological assays and radioimmunoassays gave evidence for the growth response elicited by the endogenously released salivary NGF in intact and surgically axotomized sympathetic ganglia. These results suggest that the mouse salivary NGF displays a biological activity on its target sympathetic nerve cells. PMID- 2581653 TI - Biochemical characterization and autoradiographic localization of central substance P receptors using [125I]physalaemin. AB - The binding of [125I]physalaemin to rat brain slices was investigated. Radiolabeled physalaemin bound with high affinity (Kd = 0.3 nM) to a single class of sites (Bmax = 22 fmol/mg protein). Kinetic studies indicated that binding was time-dependent and all specific binding was reversible. Pharmacology studies indicated that specific [125I]physalaemin binding was inhibited by structurally related peptides such as substance P and eledoisin. Biochemical studies indicated that specific binding of radiolabeled physalaemin was greatly reduced if the brain slices were pretreated with heat, trypsin or N-ethyl maleimide. Autoradiographic studies indicated that the [125I]physalaemin binding sites were discretely distributed throughout the brain. Highest grain densities were present in the olfactory bulb, dentate gyrus, amygdala, superficial layers of the superior colliculus, subiculum, dorsal parabrachial nucleus, locus coeruleus, nucleus tractus solitarii and dorsal horn of the spinal cord. Moderate grain densities were present in the nucleus accumbens, olfactory tubercle, pyriform cortex, striatum, hippocampus, inferior colliculus and central gray of the midbrain. Low grain densities were present in most thalamic nuclei, the substantia nigra and cerebellum. The corpus callosum and controls treated with 1 microM unlabeled physalaemin had negligible levels of binding. The unique pharmacological and regional distribution data obtained suggest that [125I]physalaemin may serve as a valuable probe to study central substance P receptors. PMID- 2581654 TI - Effect of ethanol on subthreshold currents of Aplysia pacemaker neurons. AB - The subthreshold currents in bursting pacemaker neurons of the Aplysia abdominal ganglion were individually studied with the voltage clamp technique for sensitivity to 4% ethanol. The most prevalent effect of ethanol on unclamped bursting neurons was a hyperpolarization. This was shown to be due to a decrease of a voltage independent inward leakage current. Direct measurement of the Na dependent slow inward current showed that this current was eliminated by 4% ethanol. Direct measurement of the Ca-dependent slow inward current showed that this current was substantially reduced by 4% ethanol. Injection of EGTA into cell bodies did not eliminate the ethanol-induced block of the slow inward calcium current. Thus, ethanol cannot be reducing the Ca-dependent slow inward current solely by an increase of internal calcium concentration. The effect of ethanol on voltage dependent outward current was measured by blockage of all inward current. The peak outward current was increased by ethanol. The rate of inactivation of this outward current was also increased. Calcium activated potassium current (IK(Ca)) is particularly complicated in its response to ethanol because it is dependent on both Ca and voltage for its activation. The level of IK(Ca) elicited in response to constant Ca injection was increased by ethanol treatment. The level of this current as activated by voltage clamp pulses was either increased or decreased depending on the neuron type. Ca2+ activated potassium conductance increased e-fold for a 26 mV depolarization in membrane holding potential. Ethanol decreased this voltage dependence to e-fold for a 55 mV change in potential. This result was interpreted to mean that ethanol shifted an effective Ca2+ binding site of these channels from about halfway through the membrane field to one quarter of the way across. The same theoretical approach allowed the further conclusion that ethanol caused an increased internal free calcium concentration probably by decreasing calcium binding by intracellular buffers. PMID- 2581655 TI - Ethanol administration in vivo alters calcium ions control in rat striatum. AB - The present paper investigates the effect of chronic ethanol treatment administered through drinking water on [3H]nitrendipine binding and 45Ca uptake in rat striatum. The calcium-independent [3H]nitrendipine binding was slightly increased in treated rats, while the calcium stimulation of the binding was reduced to one fifth of the controls. In striatal slices prepared from a similar group of ethanol-treated rats the K+-stimulated 45Ca uptake was greatly reduced. These results are the first evidence of calcium-antagonist binding-site 'plasticity' following an in vivo pharmacological manipulation correlated with a change in calcium ion transport. In addition, the effect of ethanol on calcium entry regulation may be a mechanism important for the understanding of its neurotoxic action. PMID- 2581656 TI - Attenuation of the reflex pressor response to muscular contraction by a substance P antagonist. AB - In chloralose-anesthetized cats, we found that D-Pro2-D-Phe7-D-Trp9-substance P (40-100 micrograms), injected intrathecally, reduced the reflex pressor response to static muscular contraction by more than half. PMID- 2581657 TI - Synaptic interaction between catecholaminergic neurons and substance P immunoreactive axons in the caudal part of the nucleus of the solitary tract of the rat: demonstration by the electron microscopic mirror technique. AB - The 'mirror technique' was applied in immunoelectron microscopy to demonstrate the synaptic relationship between neuronal structures containing catecholamines and substance P in the caudal part of nucleus of the solitary tract in the rat, using antisera against tyrosine hydroxylase and substance P. Substance P immunoreactive axon terminals were shown to make two types of synaptic contacts (asymmetrical and symmetrical) with catecholaminergic neurons. It is concluded that substance P afferents can directly affect catecholaminergic neurons in this nucleus via synapses. PMID- 2581658 TI - Reduction of [3H]substance P binding in the intermediolateral cell column after sympathectomy. AB - Guanethidine-induced destruction of sympathetic postganglionic neurons in neonatal rats leads to transneuronal degeneration of the sympathetic preganglionic neurons. Using this model, we have been able to show a approximately 35% decrease in [3H]substance P ([3H]SP) binding in the intermediolateral cell column--suggesting that sympathetic preganglionic neurons possess substance P receptors. Our results show that [3H]substance P binding in the intermediolateral cell column is dependent on the integrity of sympathetic postganglionic neurons. PMID- 2581659 TI - Rat trigeminal, olfactory and taste responses after capsaicin desensitization. AB - Experiment 1 showed that capsaicin injections severely reduced or eliminated nasal trigeminal responses to 3 odorants. Experiments 2 and 3 investigated whether desensitized animals could behaviorally detect and discriminate odors. Capsaicin treated animals had no measurable deficits in locating buried food, in odor aversion learning, or in operant odor detection and discrimination. Experiment 4 examined whether behavioral responsiveness to salty, sour and bitter tastes was affected by desensitization. Capsaicin injections did not affect responsiveness to salty or sour, but may have raised rejection thresholds for bitter. Broadly, the present results suggest that substance P-containing fibers mediate trigeminal responsiveness to odorants and irritants but that the loss of this responsiveness does not appreciably affect smell or taste, per se. PMID- 2581660 TI - Progesterone stimulates sexual behaviour in female rats by increasing 5-HT activity on 5-HT2 receptors. AB - We have investigated the possibility that there is a correlation between female sexual receptivity and CNS serotonergic activity. In ovariectomized rats primed with a submaximal steroid regime of 2 micrograms oestradiol benzoate (OB) plus 0.2 mg progesterone (P), so that only a proportion were receptive, the 5 hydroxyindoleacetic acid:5-hydroxytryptamine (5-HT) ratio in the hypothalamus was greater in the receptive compared to the non-receptive rats. When rats were primed with 10 micrograms OB alone, there was no difference in 5-HT activity in the receptive and non-receptive animals. Depletion of hypothalamic 5-HT levels by p-chlorophenylalanine methyl ester (PCPA) inhibited behaviour normally induced by OB plus P and this could be reversed by 5-hydroxytryptophan. PCPA had no effect in animals made receptive by OB alone. This indicates that P, but not OB, exerts its stimulatory effect on sexual behaviour via increasing 5-HT activity. Administration of 5-HT into the lateral, but not 3rd ventricle stimulated sexual behaviour and systemic injection of the selective 5-HT1 and 5-HT2 agonists, Ru 24969 and MK 212, inhibited and stimulated behaviour, respectively. It is suggested that 5-HT has a dual effect on female sexual receptivity acting via different systems, the inhibitory tract acting on 5-HT1 and the stimulatory tract on 5-HT2 receptors. PMID- 2581661 TI - Axonal transport of actin and regeneration rate in non-myelinated sensory nerve fibres. AB - The relationship was examined between the rate of regeneration and rate of axonal transport of actin in the sensory fibres of the rabbit vagus nerve. Regeneration rate, determined as the distance moved by [35S]methionine-radiolabelled, fast transported proteins beyond a crush, was about 3 mm/day. The rate of transport of actin, identified by two-dimensional polyacrylamide gel electrophoresis with fluorography, and DNase affinity chromatography, was 25-30 mm/day. No slower rate of actin transport comparable with regeneration rate, could be found in either control or regenerating nerves. While the provision of actin, by slow axonal transport, to the axonal growth cone may be essential for nerve regeneration, the regeneration rate is not directly controlled by the rate of actin transport. PMID- 2581663 TI - Age-related reduced affinity in [3H]nitrendipine labeling of brain voltage dependent calcium channels. AB - Literature data indicate a reduced calcium uptake in synaptosomes prepared from old rat brains. On this line, the present paper investigates the binding of ([3H]NDP) to brain synaptic membranes prepared from rats at different ages from birth up to 24 months of age. The binding is undetectable at birth but reaches within 9-18 day the values observed in adults [3H]NDP binding affinity and sensitivity to calcium were decreased in old rats (24 months). Tritiated dihydropyridines are believed to label voltage-dependent calcium channels (VDC). The observed age-related reduction in binding suggests that the characteristics of VDC in the aged brain may change. PMID- 2581662 TI - The effects of QX314 on thalamic neurons. AB - The effects of QX314 were studied in cat thalamic neurons recorded in vivo. Besides blocking Na+ spike electrogenesis, QX314 transformed spindle oscillations into a single long-lasting period of hyperpolarization that terminated with a rebound Ca2+ spike. Large sustained injections of the drug resulted in the occurrence of numerous fast prepotentials that had the characteristics of attenuated dendritic Ca2+ spikes. These effects are interpreted as resulting from the blockage by QX314 of a persistent Na+ current and a delayed rectifier K+ current which currents have already been disclosed in thalamic neurons recorded in vitro. PMID- 2581664 TI - Depolarizing prepotentials are Na+ dependent in CA1 pyramidal neurons. AB - Slow depolarizing prepotentials are important in controlling the frequency of neuronal firing in CA1 pyramidal cells. The ionic basis for subthreshold depolarizing potentials was examined in these experiments. Depolarizing prepotentials were concluded to be due to an inward Na+ current because they were blocked by reducing extracellular Na+ and by extracellular application of tetrodotoxin (TTX), and they were unaffected by blockers of inward Ca2+ currents. PMID- 2581665 TI - Retrograde axonal transport of receptor-bound opiate in the vagus and delayed accumulation in the nodose ganglion. AB - Opiate receptors measured in vivo with [3H]lofentanil in the rat vagus nerve were found to accumulate on both sides of a ligature. The time-course of accumulation was completely different in the proximal and the distal segments; the labelling was maximal 4 h after injection of [3H]lofentanil above the ligature but 16-24 h below the ligature. In unligated rats, a peak of radioactivity appeared in the nodose ganglion 16 h after injection; vagotomy, vinblastine or chronic treatment with capsaicin prevented the appearance of this delayed accumulation in the ganglion. These foregoing experiments suggest that opiate may act in the cell body of sensory neurones after being internalized at the nerve terminals and then transported retrogradely through fast axoplasmic mechanisms. PMID- 2581667 TI - Ganglio-N-tetraosylceramide (asialo GM1), an antigen common to the brain and immune system: its localization in myelin. AB - Anti-brain antisera are known to contain several interesting antibodies showing immunological cross-reactions between the nervous and hematopoietic systems, suggesting the existence of antigens common to the two systems (common antigens). One of these is the glycosphingolipid asialo GM1 (ganglio-N-tetraosylceramide, GgOse4Cer), but its location in the nervous system is unknown. Therefore, the location of the brain antigen that reacts with anti-asialo GM1 antibody was examined. On immunohistochemical treatment of sections of mouse brain with purified anti-asialo GM1 IgG, the white matter was stained specifically. Because myelin is a major component of the white matter, neutral glycosphingolipids were prepared from the myelin fraction. On thin-layer chromatography, myelin glycosphingolipids gave a band with the same mobility as asialo GM1. This band was also stained immunochemically by the peroxidase anti-peroxidase procedure using anti-asialo GM1 IgG. The glycosphingolipid of this band gave the molar ratio of sugars expected for asialo GM1. From these results it was concluded that the glycosphingolipid asialo GM1 exists in myelin. PMID- 2581666 TI - Substance P mechanisms of the spinal cord related to vasomotor tone in the spontaneously hypertensive rat. AB - This report deals with substance P (SP) mechanisms involved in regulation of vasomotor tone at the spinal cord levels in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Our results indicate the following. (1) Intrathecal injections of the SP antagonist, D-Pro,D-Trp-SP cause dose-dependent decreases in mean arterial pressure and heart rate in Sprague-Dawley rats, WKYs and SHRs; the maximal blood pressure decreases are equal to those seen after cervical spinal cord transection. (2) Intrathecal injections of this antagonist into the L1 spinal level in WKYs or SHRs that had previously had their C8 spinal cords transected caused a rise in blood pressure and heart rate, suggesting that intrinsic spinal SP mechanisms are probably not involved in vasomotor tone. (3) The intermediolateral cell column region (IML) of 16-week-old WKYs and SHRs has a single high affinity and saturable binding component with approximately the same dissociation constant (Kd = 1.21 nM for WKYs; Kd = 1.25 nM for SHRs); the SHRs showed a higher number of sites (Bmax = 24.5 fmol/mg protein) than WKY rats (Bmax = 19.9 fmol/mg protein). The Kd and Bmax obtained from IML sections from 4-week old WKYs and SHRs exhibit no differences, although their binding values with 2 nM [3H]SP are higher than those obtained from the 16-week-old animals. (4) D-Pro4,D Trp7,9-SP4-11 has the same relatively low (micromolar range) potency for displacing [3H]SP binding in the IML of WKYs and SHRs. (5) SHRs (16 weeks old) contain 20% more SP immunoreactivity in the IML than WKY rats (834 +/- 36 pg/mg protein vs 694 +/- 50 pg/mg protein); 4-week-old rats do not show such differences. The potential significance of these results is discussed in relation to the control of vasomotor tone. PMID- 2581668 TI - Inhibitory actions of tuberostemonine on the excitatory transmission at the crayfish neuromuscular junction. AB - At the crayfish neuromuscular junction, tuberostemonine, an alkaloid from Stemona japonica, reduced the amplitude of both the excitatory junctional potential (e.j.p.) and the glutamate response in a dose-dependent manner at concentrations above 0.1 mM. Tuberostemonine acted presynaptically on the crayfish neuromuscular junction to reduce a quantal content of extracellularly recorded e.j.p.s, and postsynaptically to reduce their unit size. The decay of the excitatory synaptic current was accelerated by tuberostemonine. The gradual decline of the successive glutamate currents induced by a train was facilitated by the presence of tuberostemonine even in the muscle fibre pre-treated with concanavalin A. The rate of recovery from the refractory form of the glutamate receptor to the free reactive one was slightly affected by tuberostemonine when it was determined by using a paired pulse method. The inhibitory action of tuberostemonine on glutamate responses was voltage-dependent and hyperpolarization increased the drug action. These results indicate that tuberostemonine acts in part as an open channel blocker at the crayfish neuromuscular junction. PMID- 2581669 TI - Structural effects in axoplasm of DNase I, an actin depolymerizer that blocks fast axonal transport. AB - We have studied by electron microscopy the organization of microtubules and neurofilaments in axons of giant identified neurons in Aplysia and the effect upon it of microinjected DNase I, a depolymerizer of actin filaments, to determine whether the block of fast transport caused by this agent might be due to disorganization of the cytoskeleton. Microtubules were thoroughly intermingled with the more numerous neurofilaments rather than segregated into domains. In the axon of the cell, GCN, the morphologically identifiable transmitter storage vesicles, which have been shown previously to move by anterograde fast axonal transport, were distributed non-randomly, tending to be near microtubules. They were found most frequently 10-20 nm from the nearest microtubule. When DNase I was microinjected into the axon of the cell R2, large clumps of organelles formed in areas distributed around the perimeter of the axoplasm. Microtubules were abnormally rare in those areas, though abundant elsewhere in the injected region. In some axons injected with DNase I, axoplasm separated from the axolemma at many places around the perimeter of the axoplasm. When the microtubule stabilizing drug taxol was present in the bathing medium, the inhibition of transport caused by injection of DNase I was reduced by about half. We conclude that a substantial part, at least, of this inhibition is caused by localized losses of microtubules. These results suggest that actin is more likely to play a structural role in the axon than a direct role in force generation for fast axonal transport. PMID- 2581670 TI - Ultrastructural localization of voltage-sensitive sodium channels using [125I]alpha scorpion toxin. AB - The distribution of alpha scorpion toxin (alpha-ScTx) receptors was examined in differentiated mouse neuroblastoma cell cultures (N IE 115 clone) by electron microscope autoradiography using [125I]alpha-ScTx. This neurotoxin binds specifically to voltage-sensitive sodium channels, slowing down the inactivation of the sodium permeability. Quantitative analysis demonstrated that only plasma membranes were labelled. The alpha-ScTx receptors seemed to be randomly dispersed on both cell bodies and cell processes. Microvilli protruding from the cell bodies carried more sodium channels than other parts of the membrane. The specific binding site density for alpha-ScTx varied from 4 (cell body membrane) to 13 (cell process membrane) per square micrometer. PMID- 2581672 TI - Loop arrays in mouse brain demonstrated with antisera to cytokeratins and monoclonal antibodies to several classes of intermediate filaments: strain differences and developmental expression. AB - Some monoclonal antibodies raised against mouse brain antigens display a novel loop array apparently localized within the cytoplasm of neurons in fresh frozen sections of adult mouse brain. By indirect immunofluorescence, these loops are detectable in the cerebral cortex, thalamus, brainstem, and are particularly striking in association with pyramidal neurons of the hippocampus. The loops are also seen with polyclonal antibodies to the cytokeratin class of intermediate filaments. The antibodies which react with these loops also react with ependymal cells. Western blot analysis of crude insoluble cytoskeletal components of mouse brain with antibodies of cytokeratins confirm the presence of reactive bands in the range of 40-60 kdalton, appropriate in molecular weight for this class of cytoskeletal filaments. This evidence suggests that the loops share antigenic determinants with non-neural cytokeratins. During development, immunoreactive structures are first seen as small punctate or curvilinear profiles, which change into a loop array at approximately 14 days postnatal age in several mouse strains. However, in 8 of 15 different mouse strains, these immature punctate profiles remain without morphological alteration to loops throughout adult age. The F1 crosses between strains with and without the loops develop loops, but on average they are of smaller size than in the positive parent. PMID- 2581671 TI - Ultrastructure of transganglionic HRP transport in cat trigeminal system. AB - The ultrastructure of transganglionic transport of horseradish peroxidase (HRP) from the inferior alveolar (IA) nerve to the brainstem is being studied in the cat. The IA nerve was soaked in an HRP solution and following a two-day survival the animal was perfused transcardially with a paraformaldehyde-glutaraldehyde solution. The tissue was immediately dissected and postfixed for 1-3 h in perfusate. Sections of 75 micron thickness were cut with a Vibratome and reacted utilizing tetramethyl benzidine (TMB) as the chromagen. Optimum results for electron microscopy were obtained by osmication in a pH 6.0, 1% osmium tetroxide solution for 45 min at 45 degrees C, followed by rapid dehydration and embedment in Epon. The resulting HRP-TMB reaction product was characterized and identified ultrastructurally in ganglion cells, peripheral and central axons and in brainstem terminals. The HRP-TMB reaction product varied in density but had consistent crystalline-like laminations of a repeating unit and characterized by a membrane 4-5 nm in diameter. Some of the HRP-TMB reaction product found in terminals and axons was below the limit of resolution of the light microscope. PMID- 2581673 TI - Lumbar cerebrospinal fluid homovanillic acid concentrations are higher in female than male non-human primates. AB - Concentrations of homovanillic acid and 5-hydroxyindoleacetic acid were determined in lumbar cerebrospinal fluid from intact male and female Macaca nemestrina. Concentrations of homovanillic acid, but not 5-hydroxyindoleacetic acid were significantly higher in the females under baseline conditions. Following probenecid treatment, 5-hydroxyindoleacetic acid concentrations were significantly elevated over baseline conditions in both sexes although only homovanillic acid concentrations were significantly higher in the female monkeys. PMID- 2581674 TI - Absence of postnatal death among motoneurones supplying the inferior gluteal nerve of the rat. AB - Motoneurones innervating the caudal part of the gluteus maximus muscle of 0-2 day, 10-12 day and 2-3-month-old rats were labelled by a half-hour application of a solution of 30% horseradish peroxidase (HRP) and 2% lysophatidylcholine delivered by suction electrode to the cut inferior gluteal nerves. The numbers of motoneurones labelled 24-48 h later were not significantly different in the 3 age groups (mean = 58.75, 54.0, 57.5, respectively). When a simple 30% HRP solution was used in adult rats, the number of motoneurones labelled was significantly less (mean = 48.75). In contrast, application of 0.5 microliter of HRP in a pledget of gelfoam to either the cut or uncut inferior gluteal nerve of neonates labelled large numbers of motoneurones, presumably by diffusion into nearby muscles. It is concluded that no death of motoneurones innervating the gluteus maximus muscle occurs postnatally, and that spread of HRP to neighbouring muscles can give rise to spuriously high motoneurone counts in neonates, and that incomplete uptake or transport of HRP in adults can lead to incorrectly low counts. PMID- 2581675 TI - Functional properties of newly inserted acetylcholine receptors in embryonic Xenopus muscle cells. AB - Single-channel properties of nicotinic acetylcholine receptors in Xenopus embryonic muscles were investigated by the patch clamp technique. Dissociated muscle cells were prepared from embryos in early stages of development (stages 18 19) before innervation takes place, and were cultured without neurons for 4-6 days. Despite the absence of innervation in their history, the cells displayed two classes of acetylcholine receptors, one characterized by a small channel conductance (32 pS), and the other by a large conductance (48 pS) (13 degrees C; agonist, suberyldicholine). The small conductance events had longer mean open times than the large conductance events. Both types of channels had reversal potentials near -15 mV. Hyperpolarization prolonged the open times of both channels; an e-fold change was produced by a 70-80 mV polarization. In order to characterize channel properties of newly inserted receptors, existing receptors were inactivated by alpha-bungarotoxin, and recordings were made over the next 4 8 h. These new receptors already exhibited the two classes of characteristics, which were similar to those of old acetylcholine receptors. These results suggest that innervation is not a prerequisite for expression of the two classes of acetylcholine receptors, and indicate that receptors become functionally mature soon after insertion into the plasma membrane. These results of 'metabolically' new receptors are in sharp contrast with the data of Leonard et al. (Soc. Neurosci. Abstr., 9 (1983) 1180), who reported that 'ontogenetically' new acetylcholine receptors had much longer open times than old receptors. PMID- 2581676 TI - Chronic treatment with ACTH1-24 does not produce permanent damage to the developing rat brain. AB - Permanent effects of ACTH1-24 on the developing rat brain were investigated. Rats were injected with 20 IU/kg of ACTH1-24 daily for 4 weeks starting at two days of age. Brain weight, protein, DNA and RNA contents, contents of monoamines and their metabolites, 2',3'-cyclic nucleotide 3'-phosphohydrolase and glutamic acid decarboxylase activities were measured at 24 h and 8 weeks after the last injection. There were no significant changes in these indicators compared to saline-injected controls. These results suggest that chronic treatment with ACTH1 24 does not permanently damage the developing rat brain. PMID- 2581678 TI - [Effects of rabies infection on the metabolism of the host-cell: does inhibition of cellular RNA synthesis take place?]. AB - Acute infection of cloned BHK21 cells with rabies virus (CVS strain) resulted in a reduction in the amount of cellular RNA, not so rapid and pronounced as with another rhabdovirus, vesicular stomatitis virus (VSV). This decrease in the amount of cellular RNA was shown to be caused by a differential membrane permeability of infected and uninfected BHK21 cells to [3H]-uridine and by a real inhibition of cellular RNA synthesis. PMID- 2581677 TI - Stabilization of TMB reaction product for electron microscopic retrograde and anterograde fiber tracing. AB - Use of the highly sensitive tetramethylbenzidine (TMB) method of horseradish peroxidase histochemistry for electron microscopy has been limited by the solubility of the reaction product in aqueous and alcoholic solutions. We have found that following the TMB reaction with a diaminobenzidine-cobalt (DAB-Co) step causes the TMB crystals to become coated with DAB-Co. The resultant reaction complex is insoluble, and easily localized using electron microscopy. By systematically varying the pH at which the TMB reaction is run, the size and shape of the reaction complex can be controlled. The pH 4.0 reaction complex was the most suitable for electron microscopic identification of labeled structures less than 1.0 micron in diameter (e.g., axon terminals). PMID- 2581679 TI - [Experimental demonstration of the annual characteristic of the lines of arrest of skeletal growth in Rana esculenta (Amphibia, anura)]. AB - Different vital fluorescent labelling (tetracycline, calcein, xylenol orange, alizarine red S) have been injected in a series of young growing green frogs, caught near Paris and kept for 2 years in captivity under conditions quite similar to natural ones. The study of femur and phalanx has been carried out by ground sections observed in UV light and then colored with hematoxyline. The comparison between UV and transmitted light observations shows that the arrested growth lines are annual, laid during winter and never completely destroyed by bone remodelling. Then, they constitute a valuable criterion to assess the age of the individual. PMID- 2581680 TI - [Spinal anesthesia and morphine analgesia in prostatic surgery]. AB - The authors compare the effects of either 0,5 or one milligram of intrathecally injected morphine on the post-operative course of 45 patients scheduled for transvesical prostatectomy. The patients were randomly assigned to three groups. Group A patients served as reference and were anesthetized by intrathecal injection of prilocaine 100 mg. Group B and C patients underwent the same anaesthetic procedure but prilocaine was injected simultaneously with either 0,5 (B) or one milligram (C) of morphine. Group A patients experienced postoperative pain for eighteen hours and requiring a mean subcutaneous dose of 20 mg of morphine. B and C patients had a satisfactory degree of analgesia. Nevertheless, there was a statistically significant difference of analgesia scores between groups C and B. The group C patients remained free of respiratory impairment. One mg of intrathecal morphine seems optimal for analgesia after prostatectomy. PMID- 2581681 TI - Relationship between toluidine blue-stained calcification fronts and tetracycline labeled surfaces in normal human iliac crest biopsies. AB - The relationship between toluidine blue-stained calcification fronts and tetracycline labeling was examined in iliac crest biopsies from 56 normal subjects aged 19-80 years, all of whom had received double tetracycline labeling. Sections were quantitated using an eye-piece graticule and all values were expressed as a percentage of osteoid surface. Values for double plus single tetracycline-labeled surfaces were lower than those obtained for toluidine blue stained calcification fronts in 66% of subjects, although the difference between the two measurements was not statistically significant. Values obtained for calcification fronts demonstrated by toluidine blue staining were significantly greater than those obtained for single, double, and double plus half single tetracycline-labeled surfaces. No significant correlation could be demonstrated between toluidine blue-stained calcification and tetracycline-labeled surfaces. In conclusion, the fraction of osteoid bearing a tetracycline label differed from that showing a toluidine blue-stained calcification front and no correlation could be demonstrated between the two measurements. These differences may arise from methodological problems associated with their demonstration and identification; alternatively their lack of similarity might reflect uptake of stain and tetracycline at different sites within the calcification front. Which of the two parameters most accurately represents the active mineralizing surface is unknown. PMID- 2581683 TI - Drug management of pain in cancer patients. PMID- 2581682 TI - Ultrastructural distribution of acidic glycosaminoglycans associated with matrix vesicle-mediated calcification in mouse progenitor predentine. AB - The ultrastructural localization of acidic glycosaminoglycans, presumed to be proteoglycans, was examined during initial matrix vesicle-mediated calcification in dentine, by using ruthenium red (RR) staining, high iron diamine thiocarbohydrazide silver proteinate (HID-TCH-SP) staining, and an enzymatic digestion method. Progenitor predentine 2-10 micron width of developing mouse molar tooth germs was used throughout the present study. The outer surface membrane of the intact matrix vesicles had a strong affinity for RR. The RR positive materials appeared beaded and extended perpendicularly from the vesicle membrane. They tended to disappear with the disruption of the vesicular membrane, which resulted from overextension due to needle-like, crystal-like structures. The HID-TCH-SP stain deposits, approximately 10 nm in diameter, were densely distributed around the intact matrix vesicles, though few were found inside them. Some matrix vesicles that were presumably disrupted, however, contained smaller stain deposits. On the outer surface membrane of the disrupted vesicles, HID-TCH SP stain deposits were fewer in number. The results obtained from enzymatic degradation studies showed that the anionic materials on the outer surface membrane of the matrix vesicles were represented by chondroitin-4-sulfate and/or chondroitin-6-sulfate. We suggest that chondroitin sulfates attached to the outer leaflet of the vesicular membrane play an important role during the incipient stage of the matrix vesicle-mediated calcification process. PMID- 2581684 TI - A human embryonal-yolk sac carcinoma model system in athymic mice. AB - Two new human cell lines (1411H and 1411HRQmet) have been established from a patient with metastatic testicular cancer whose primary and metastatic histology included seminoma, teratoma, embryonal carcinoma (EC), and yolk sac tumor (YST). In vitro, the cells have been maintained for more than 70 passages, produce alpha fetoprotein (AFP) and human chorionic gonadotropin (hCG), and have a human karyotype. When 2 X 10(7) cells of either line are inoculated into athymic mice, 87.5% of the animals (21/24) develop tumors. Initially 80% to 90% of the mass is EC, whereas the central portion is YST. After 90 to 390 days in vivo, the tumors achieve a large volume (2.13 +/- 0.97 cm3), become cystic, and undergo histologic change. The peripheral rim of the mass remains EC, but the central 80% to 90% becomes YST. The sera of tumor-bearing mice were positive for hCG and AFP in 11% and 38% of animals, respectively. Tumor cyst fluid was positive for hCG and AFP in 87% and 59% of animals, with mean values of 108 mIU/ml and 2,478 ng/ml, respectively. Tumor cyst fluid also contained placental alkaline phosphatase and human fibronectin. These two cell lines are useful for studies on the interrelationship of EC and YST and the differentiation of human germ cell cancer. PMID- 2581685 TI - Histiocytoid hemangioma of the heart with peripheral eosinophilia. AB - A histiocytoid hemangioma of the heart is reported, which was found incidentally in a man with unusually high eosinophilia. The eosinophilia subsided dramatically following removal of the tumor. The "histiocytoid" or the "epithelioid" appearance of the tumor cells and the presence of vacuolated cells were the characteristic microscopic features. The endothelial origin of this tumor was verified by positive immunostaining for factor VIII-related antigen and ultrastructural demonstration of intracytoplasmic lumen formation, abundant cytoplasmic filaments, pinocytotic vesicles, and prominent basal lamina. The presence of mitotic activity, cellular pleomorphism, and tumor necrosis raised the possibility of its malignant potential. The occurrence of this tumor in the heart may be mistaken for a myxoma clinically and a metastatic carcinoma pathologically. PMID- 2581687 TI - How things have changed! PMID- 2581686 TI - Genetic predisposition to acute lymphocytic leukemia in American blacks. A Pediatric Oncology Group study. AB - Recent reports have shown an association between genes lying within the major histocompatibility complex (MHC), particularly HLA and factor B (Bf), and acute lymphocytic leukemia (ALL) in white children. The frequencies of Bf and complement component C4 phenotypes in 90 black American children with ALL were examined to determine if a genetic association existed. The Bf and C4 results for the black children with ALL were compared with frequencies in healthy black Americans from the same geographic region. The BfF allele was carried by 95.6% of the black ALL patients compared with 86.1% of the controls (P = 0.017; relative risk = 3.5). In contrast, only 2.2% of the patients with ALL were homozygous for BfS compared with 9.8% of the controls (P = 0.043; relative risk = 0.2). These findings are similar to those observed in white American children. The C4A6 phenotype was found in 11.9% of the black children with ALL compared with 0.6% of the controls (P = 0.0026; relative risk = 22.7). These findings represent the first reported association of a particular allele whose gene lies within the MHC with ALL in black American children. The results suggest that the occurrence of ALL in black American children may be partially due to a genetic influence. PMID- 2581688 TI - Cell shape, the complex cellular networks, and gene expression. Cytoskeletal protein genes as a model system. PMID- 2581691 TI - A model of continuity of care for cancer patients with pain and neuro-oncologic complications. PMID- 2581689 TI - DNA adduct formation in rat, human and hamster pancreas treated with methylnitrosourea. AB - The methylation of cellular macromolecules with dimethylnitrosamine (DMN) and methylnitrosourea (MNU) was studied in organ cultured rat, hamster and human pancreatic explants. At concentrations of DMN and MNU that caused similar methylation of protein in human explants DMN caused only 2.6% and 0.3% of the methylation of DNA and RNA that was produced by MNU. The DNA of explants treated with MNU was analyzed. The O6-methylguanine (O6-MeG)/7-methylguanine (7-MeG) ratio was greater in the hamster DNA than in DNA isolated from either rat or human. The time course of removal of methyl adducts from DNA was followed for 6 h after treatment with MNU. No decline in O6-MeG occurred during this period in hamster explants, although there was a decline in the content of 7-MeA and 3-MeA, whereas there was removal of O6-MeG in the DNA from human pancreas explants. PMID- 2581690 TI - Selective resistance to cytotoxic agents in hepatocytes isolated from partially hepatectomized and neoplastic mouse liver. AB - Hepatocytes were isolated from B6C3F1 male mouse neoplastic livers (containing hepatocellular adenomas and carcinomas) or two-thirds partially hepatectomized livers and tested in primary culture for their cytotoxic response to hepatotoxins. Partially hepatectomized mouse hepatocytes were less sensitive to lindane, methotrexate, diethylnitrosamine and adriamycin, and more sensitive to cycloheximide compared to normal mouse hepatocytes. Neoplastic hepatocytes were less sensitive to lindane and methotrexate, did not differ in cytotoxic response to diethylnitrosamine and adriamycin and were more sensitive to cycloheximide compared to normal mouse hepatocytes. PMID- 2581692 TI - Intraoral demineralization and maltose clearance from wheat starch. PMID- 2581693 TI - Heterogeneity of the rat macrophage antigenic specificity of resident peritoneal and pleural macrophages. PMID- 2581694 TI - Lectin histochemistry of secretory and cell-surface glycoconjugates in the ovine submandibular gland. AB - Information about the chemical structure of ovine submandibular glycoconjugates was obtained in situ by means of a battery of peroxidase-conjugated lectins with affinity for specific terminal or internal sugars or sugar sequences in conjunction with neuraminidase digestion and periodate oxidation. Stored secretions in all mucous acinar cells contained disaccharide side chains consisting of N-acetylneuraminic acid linked to penultimate alpha-N acetylgalactosamine localizing the predominant disaccharide demonstrated biochemically. A previously unrecognized disaccharide consisting of terminal N acetylneuraminic acid and penultimate beta-galactose was found in 20-30% of mucous acinar cells. Occasional clusters of acini composed purely of serous cells contained an additional unrecognized glyco-conjugate with oligosaccharides terminated by sialic acid with O-acetylated polyhydroxyl side chains and penultimate beta-galactose. Serous demilunes, however, lacked detectable complex carbohydrate other than glycogen. Terminal sialic acid-beta-galactose dimers were present on the apical surface of all ducts except for intercalated ducts coated only with neutral glycoconjugate. Fucose assayed biochemically as a minor component occurred in abundance in glycoconjugates at the apical surface of all intercalated and most striated duct cells and within some striated duct cells. Terminal alpha-galactose not previously detected biochemically was localized at the apex of all duct cells. These results provide new knowledge concerning the structure of ovine submandibular glycoconjugates. They also illustrate the value of histochemical methods for elucidating the diversity of complex carbohydrates in an organ, locating different glycoconjugates in different types or subtypes of epithelial cells and demonstrating intracellular sites that contain complex carbohydrate. PMID- 2581695 TI - A one and a half receptor model for MHC-restricted antigen recognition by T lymphocytes. PMID- 2581696 TI - Stringent control of bacterial transcription. PMID- 2581697 TI - Metallothioneins: proteins in search of function. PMID- 2581698 TI - Induction of natural killer cell activity of thoracic duct lymphocytes by polyinosinic-polycytidylic acid (poly(I:C)) or interferon. AB - Natural killer (NK) cell activity of thoracic duct lymphocytes (TDL) was examined in normal mice and in mice treated with polyinosinic-polycytidylic acid (poly(I:C) and interferon (IFN). TDL from mice treated with phosphate-buffered saline (PBS) expressed little or no NK cell activity against YAC-1 target cells at effector-to-target ratios of up to 200:1, even after in vitro treatment with murine L-cell IFN. In contrast, TDL from poly(I:C)- or IFN-treated mice expressed significant NK activity, which correlated with the significantly higher NK activity of splenocytes from these mice compared to the NK activity of splenocytes from PBS-treated mice. These data indicate that although TDL from normal mice express no detectable NK cell activity, NK cell activity can be induced in TDL by in vivo treatment with poly(I:C) or IFN. PMID- 2581699 TI - Transfer of experimental allergic neuritis with P2-reactive T-cell lines. AB - Experimental allergic neuritis (EAN) was induced in normal Lewis rats by systemic passive transfer of T-cell lines responding to P2 protein. These cells had predominantly helper phenotype and could induce EAN within 7 days following adoptive transfer. There was no anti-P2 antibody response in the recipients of the P2-reactive cells recovered from donors with high anti-P2 antibody levels. This study provides direct evidence that T cells are important for the induction of EAN. Furthermore, there was no evidence of a pathogenic role for anti-P2 antibody in passive EAN. PMID- 2581700 TI - Thymus hormones do not induce proliferative ability or cytolytic function in PNA+ cortical thymocytes. AB - A variety of thymus hormone preparations, as well as drugs known to perturb cell differentiation, were tested for their ability to induce nonfunctional cortical thymocytes to become functional precursor cells. Murine cortical thymocytes, defined as the high peanut agglutinin (PNA) binding or as the low H-2K, major [86%] thymocyte subpopulation, were isolated by fluorescence-activated cell sorting. Their function was assessed in a high cloning efficiency, growth factor saturated, concanavalin A-stimulated limit-dilution culture system, determining the number of precursors of extended clones (PTL-p), or determining with a lectin mediated tumor-lysis readout the number of precursors of cytolytic clones (CTL p). The hormone preparations tested were crude or partially purified culture supernatants from thymus "epithelial" monolayers (TES), soluble extracts of thymic nonlymphoid tissue (STF), semipure thymus humoral factor (THF), and the pure peptides thymopoietin 32-36 (TP5) and "facteur thymique serique" (FTS). These preparations were either added directly to the limit dilution cultures, or were first preincubated with the cells, which were then subjected to limit dilution culture. In no case did the hormone preparations cause any increase in the level of PTL-p or CTL-p in the PNA+ or low H-2K thymocyte population, even though a conversion of only a few percent to functional cells could have been detected. Two possible explanations are considered. One is that the main function of these materials is to control post-thymic peripheral T cells, rather than to induce intrathymic differentiation. Another is that the typical cortical thymocyte is beyond the stage at which thymocytes can be induced by hormones, a view that is strengthened by the failure of either 5-azacytidine or the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate to activate these cells. In this latter explanation the true intrathymic target of hormone action may be an earlier, and very minor, thymus subpopulation. PMID- 2581701 TI - Effect of monoclonal antibodies (MoAb) to class I and class II HLA antigens on lectin- and MoAb OKT3-induced lymphocyte proliferation. AB - We have examined the effect of several monoclonal antibodies (MoAb) to monomorphic determinants of class II HLA antigens, and MoAb to monomorphic determinants of class I HLA antigens and to beta-2-microglobulin (beta 2-mu) on lectin- and MoAb OKT3-induced proliferation of human peripheral blood mononuclear cells (PBMNC) and cultured T cells (CTC). Some, but not all, anti-class II HLA MoAb inhibited the proliferative response of PBMNC to MoAb OKT3 and pokeweed mitogen (PWM). The degree of inhibitory effect varied considerably. This effect was not limited to anti-class II HLA MoAb since anti-class I HLA MoAb and anti beta 2-mu MoAb also inhibited MoAb OKT3- or PWM-induced proliferative responses. In contrast, the response of PBMNC to phytohemagglutinin (PHA) and concanavalin A (Con A) was not blocked by any anti-class II HLA MoAb. However, some anti-class II HLA MoAb also inhibited the proliferative response of CTC plus allogeneic peripheral blood adherent accessory cells (AC) to PHA or Con A as well as to MoAb OKT3 or PWM. This may be attributable to the substantially greater class II HLA antigen expression by CTC than by fresh lymphocytes. Pretreatment of either CTC or AC with anti-class II HLA MoAb inhibited OKT3-induced proliferation. In contrast, pretreatment of CTC, but not AC, with anti-class I HLA MoAb inhibited the proliferative response of CTC to OKT3. Pretreatment of CTC with anti-class I HLA MoAb inhibited PHA-, Con A and PWM-induced proliferation, to a greater degree than the anti-class II HLA MoAb. It appears as if lymphocyte activation by different mitogens exhibits variable requirements for the presence of cells expressing major histocompatibility determinants. Binding of Ab to membrane markers may interfere with lymphocyte-AC cooperation, perhaps by inhibiting binding of mitogens to their receptors or by interfering with lymphocyte and AC function. We also have examined the role of class II HLA antigens on CTC by depleting class II HLA-positive cells. As expected, elimination of class II HLA positive AC with anti-class II HLA MoAb plus complement caused a decrease in proliferation of CTC in response to all the mitogens tested. In contrast, elimination of class II HLA-positive CTC was shown to clearly increase proliferation of CTC, perhaps because this may deplete class II HLA-positive suppressor cells. PMID- 2581702 TI - Combinations of two synthetic adjuvants: synergistic effects of a surfactant and a polyanion on the humoral immune response. AB - Synergistic effects of two synthetic adjuvants, dimethyldioctadecylammonium bromide (DDA) and dextran sulfate (DXS) on the humoral response to sheep red blood cells (SRBC) were investigated. Mice received intraperitoneal (ip) injections of adjuvant and antigen simultaneously. The number of plaque-forming cells (PFC) in the spleen were determined 5 days later and circulating anti-SRBC antibodies were measured till 16 weeks after immunization. Although combinations of DDA and DXS were very effective in enhancing the PFC response to both moderate (2 X 10(7] and low (2 X 10(6] doses of SRBC, synergy between the adjuvants was only observed at the low dose of SRBC. Optimal augmentation of the primary response to the low antigen dose was evoked by the combination of the highest dose tested of either adjuvant (1 mumol DDA and 1 nmol DXS) resulting in a 560 fold increase of the number of PFC in the spleen as compared to controls. Even combinations of relatively small amounts of both adjuvants were very effective in augmenting the response to SRBC. Mice receiving half the amounts of both adjuvants with 2 X 10(6) SRBC displayed increased numbers of PFC in the spleen at Day 5 as well as increased titers of total anti-SRBC antibodies at Week 1 and Week 2 and 2-mercaptoethanol-resistant antibodies from Week 4 till Week 16 as compared to the calculated sum of responses in mice which received either DDA (0.05 mumol per mouse) or DXS (0.05 nmol per mouse). The mechanism behind the synergy between these adjuvants is discussed and the possibility of discerning adjuvants on their modes of action is suggested. PMID- 2581703 TI - A unidirectional carrier effect. AB - A surprising unidirectional carrier effect has been observed in the antibody response to myoglobin-ferritin conjugate. This conjugate serves as a hapten carrier complex for myoglobin-specific T cells to help ferritin-specific B cells make anti-ferritin antibodies, but it does not function for ferritin-specific T cells to help myoglobin-specific B cells to make anti-myoglobin. Therefore, myoglobin-ferritin does not bypass the Ir gene defect of low responders to myoglobin. In contrast, myoglobin-fowl gamma-globulin does induce anti-myoglobin antibodies in low responder mice and thus bypasses the Ir gene defect. Both complexes are covalently coupled. Since the myoglobin-ferritin conjugate serves for myoglobin-specific T cells to help myoglobin-specific B cells, the myoglobin in the conjugate is not altered in a way that would prevent recognition by myoglobin-specific B cells. Similarly, the conjugate serves for ferritin-specific helper T cells to help ferritin-specific B cells, so it can be recognized functionally by ferritin-specific T helper cells. Explanations such as unidirectional induction of or sensitivity to bystander help, or T-cell suppression, have been excluded. While the explanation for this unexpected observation is not yet certain, several possibilities are discussed to explain this novel phenomenon, which is believed to be the first example of such a unidirectional carrier effect between two proteins. PMID- 2581704 TI - An anti-human monocyte/macrophage monoclonal antibody, reacting most strongly with macrophages in lymphoid tissue. AB - In this report, we have described monoclonal antibody (mAb) 24 which bound specifically to a 174,000 polypeptide present on 45 +/- 16% of human monocytes. Expression of the 24 molecule increased on monocytes when they were cultured. When tissues were examined using immunohistochemical techniques, macrophages (Mph) associated with skin and with lymphoid organs strongly expressed the mAb 24 molecule, whereas, Mph in nonlymphoid organs were only weakly positive. mAb 24 reacted with cells of Mph morphology plus cells of interdigitating appearance in T-cell areas, suggesting that these cells might belong to the Mph cell lineage. There was no reaction with other types of cells, such as Langerhans cells, osteoclasts, dendritic reticulum cells, and endothelial cells. The fact that the molecule recognised by mAb 24 is particularly associated with Mph in lymphoid tissue suggests that it might have a function in immune responses. PMID- 2581705 TI - Purification of human interleukin 1 from human monocyte culture supernatants and identity of thymocyte comitogenic factor, fibroblast-proliferation factor, acute phase protein-inducing factor, and endogenous pyrogen. AB - Human interleukin 1 (IL-1) in lipopolysaccharide and silica-stimulated human peripheral blood monocyte culture supernatants was purified to apparent homogeneity by sequential chromatography using DEAE-Sephacel, Sephacryl S-200, CM high-performance liquid chromatography (HPLC), and hydroxyapatite-HPLC. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) yielded only one band detectable by silver staining with an apparent molecular weight (MW) of 19,000 under nonreducing conditions. IL-1 activity was eluted from a single site from PAGE performed in the absence of SDS. About 4.4 micrograms of IL 1 was purified from 5.0 liters of culture supernatant of lipopolysaccharide- and silica-stimulated human peripheral blood monocytes, with 46.6% recovery of biological activity. The specific activity of the purified IL-1 was 4.3 X 10(7) U/mg protein. Amino acid composition analysis of the purified human IL-1 was similar to that previously described for murine IL-1. The purified IL-1 exhibited the biological activities previously attributed to IL-1, including thymocyte comitogenic activity, fibroblast proliferation activity, acute-phase protein (haptoglobin)-inducing activity, and endogenous pyrogen activity. PMID- 2581706 TI - Antigen-specific augmentation of murine immediate hypersensitivity-like footpad reaction by a T-cell factor in the culture supernatant of immune spleen cells. AB - An antigen-specific factor capable of augmenting delayed-type hypersensitivity (DH) in the culture supernatants from immune spleen cells and erythrocyte antigen has been found. These culture supernatants also augmented an immediate hypersensitivity-like reaction which appeared in advance of the classical DH reaction. In this paper, the basic characteristics and cells producing the augmentation factor (IAF) involved in immediate hypersensitivity-like reaction were investigated. Maximum activity of IAF was detected in a supernatant from 24 hr culture of immune spleen cells and antigen. In vitro antigen stimulation was essentially required for the production or release of IAF. IAF showed antigen specificity. IAF was produced or released by T cells. In addition to these facts, the DH-augmentation factor proved to be a T-cell product. PMID- 2581707 TI - The modulation of membrane Ia on human B lymphocytes. AB - Using flow cytometry techniques, changes in surface Ia (DR and DS) expression on human B lymphocytes were correlated with changes in the cell cycle following stimulation with anti-mu. The effect of interleukin (IL)-1, IL-2, B-cell growth factor (BCGF), and interferons on Ia expression on resting B cells was also examined. A population of resting B lymphocytes was cultured in vitro with 100 micrograms/ml of anti-mu and immunofluorescently stained for DR and DS at various times following stimulation. Detectable increases in DR and DS expression were found within 8 hr, and the major increases (twofold and fourfold) in DR and DS expression occurred over the next 48 hr. Using cell cycle inhibitors and propidium iodide staining, it was demonstrated that the enhanced DR and DS expression following anti-mu stimulation began during G0 to G1 transition and increased as the cells progressed through G1 phase. During S and G2/M phases, there were minimal further increases in surface Ia. Although prolonged exposure of B cells to anti-mu was required for cellular activation, cell size enlargement, and progression into S phase, a brief exposure to anti-mu, insufficient for cellular activation, markedly enhanced Ia expression. Thus anti mu-stimulated resting human B lymphocytes rapidly increase their surface Ia expression. This increase occurs predominantly prior to entrance into S phase and can occur in the absence of significant cellular activation. Interferons have been reported to modulate surface Ia expression on a human lymphoid cell line and on monocytes and supernatants with BCGF activity to enhance surface Ia expression on murine B cells; however, neither alpha-interferon, gamma-interferon, IL-1, IL 2, nor BCGF modified surface DR expression on normal resting human B cells. PMID- 2581708 TI - Production and characterization of a unique monoclonal antibody against human B cells (33.2.1). AB - A monoclonal antibody specific for a polymorphic antigen on human B cells (33.2.1) was produced and characterized. By flow cytometry, 33.2.1 was found to react with peripheral blood B cells, monocytes, and Epstein-Barr virus (EBV) transformed B-cell lines, but not with peripheral blood T cells, mitogen activated T cells, or allo- or autoactivated T cells. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that 33.2.1 recognizes a noncovalently bound bimolecular complex composed of an alpha chain of about 32 kDa and a beta chain of about 28 kDa. The failure of anti-HLA-DR, anti-Leu-10, and anti-HLA-DC1 to remove the 33.2.1 antigen by sequential immunoprecipitation suggests that 33.2.1 recognizes a distinct molecule rather than a different epitope on either HLA-DR or DS/DC/MB. In T-cell-independent B cell activation systems, preincubation with 33.2.1 markedly inhibited RNA and DNA synthesis as well as polyclonal Ig production. In contrast, anti-HLA-DR was inhibitory only when it was present throughout the culture, but not when it was used for preincubation. Anti-Leu-10 led to only moderate inhibition. These results suggest that 33.2.1 recognizes a unique Ia-like antigen critical for B cell activation. PMID- 2581709 TI - Recombinant interleukin 2 rapidly augments human natural killer cell activity. AB - Recombinant human interleukin 2 (r-IL-2) rapidly stimulated human natural killer cell activity in vitro. Augmentation of NK activity occurred within 1 hr of preincubation with r-IL-2. Responsive killer cells were typical NK cells as shown by cell fractionation procedures. These included Percoll density gradient separation and depletion of OKT3+ T cells by an indirect rosetting method. Analysis with a panel of polyclonal and monoclonal antibodies against alpha and gamma interferon revealed that this early enhancement of NK activity by r-IL-2 was independent of the production of both types of interferon. PMID- 2581710 TI - The isolation of intrahepatic biliary epithelial cells from normal rat livers. AB - A method is described for the isolation of biliary epithelial cells from rat livers by sequential treatment with EGTA, collagenase-hyaluronidase, trypsin, and deoxyribonuclease I and final separation on a discontinuous Percoll gradient using prekeratin antibodies as an immunohistochemical marker for these cells. PMID- 2581711 TI - Reduction in RNA synthesis following red cell-mediated microinjection of antibodies to RNA polymerase I. AB - Antibody molecules directed against RNA polymerase I, the enzyme responsible for rRNA synthesis, were introduced into rat hepatoma cells by red cell-mediated microinjection. Access of the antibodies to the nucleolus, the site of rRNA synthesis, was facilitated by microinjecting mitotic cells. Using indirect immunofluorescence, anti-RNA polymerase I immunoglobulins, but not control immunoglobulins, were found localized in the nucleoli of microinjected cells. To assess whether intracellular antibodies could alter RNA synthesis, cultures were labeled with [3H] uridine at various times after microinjection. Reduction in RNA synthesis, relative to cells microinjected with non-immune immunoglobulins, was observed within three hours. These results demonstrate that antibodies introduced into the cytoplasm of mitotic cells via red cell-mediated microinjection have free access to nuclear components and that they remain functional within the nuclei of living cells. PMID- 2581712 TI - Isolation and initial characterization of a temperature-sensitive mutant of mouse FM3A cells defective in cytokinesis. AB - A temperature-sensitive mutant, designated tsFT101, was isolated from a mouse mammary carcinoma cell line, FM3A, and given an initial characterization. In this cell line, cytokinesis was blocked at a non-permissive temperature (39 degrees C), but DNA synthesis and nuclear division proceeded normally for at least 24 h at 39 degrees C as detected respectively by autoradiography and cytofluorometric analysis. As a result, multinucleate cells accumulated at 39 degrees C (more than 95% in 36 h). When the culture was returned to a permissive temperature (33 degrees C) after 24 h of arrest at 39 degrees C, cytokinesis was resumed and there was a rapid decrease in the number of multinucleate cells. At 39 degrees C, tsFT101 cells had less F-actin than cells at 33 degrees C, indicative of the existence of an abnormality in actin polymerization in this mutant. PMID- 2581713 TI - [Use of linguistics in rehabilitation of aphasia]. PMID- 2581714 TI - In vitro miscoding of alkylthymines with DNA and RNA polymerases. AB - A series of poly(dT,RdT) polynucleotides containing O2-, 3- and O4-methyl- or ethyldeoxythymines have been prepared and used as templates for Pol I, Pol alpha and Pol R to investigate the miscoding properties of these modified bases with the different nucleotide polymerising enzymes. Only O4-alkylthymine (O4-RT) leads to a large number of errors (incorporation of dGMP with a mutagenic efficiency approaching unity). O2-RT has a very much lower, but none-the-less significant, mutagenic efficiency and 3-RT does not lead to errors with the DNA polymerases. All alkylthymines lead to significant errors with the RNA polymerase. The results confirm conclusions concerning the promutagenic nature of the alkylthymines and that the reported differences in their promutagenicity with the various polymerases reflect different specificities of the nucleotide polymerising enzymes used. PMID- 2581715 TI - [Silver nitrate staining of influenza virus RNA in polyacrylamide gel]. PMID- 2581716 TI - [Treatment of the side effects of the chemotherapy of trophoblastic tumor with traditional Chinese medicine and western medicine]. PMID- 2581718 TI - Inotropic effect, binding properties, and calcium flux effects of the calcium channel agonist CGP 28392 in intact cultured embryonic chick ventricular cells. AB - CGP 28392 is a recently described dihydropyridine derivative with positive inotropic properties. To study the mechanism of action of this putative calcium channel agonist, we have related the effects of CGP 28392 on contraction (measured with an optical video system) and radioactive calcium uptake to ligand binding studies in cultured, spontaneously beating chick embryo ventricular cells. CGP 28392 produced a concentration-dependent increase in amplitude and velocity of contraction (EC50 = 2 X 10(-7) M; maximum contractile effect = 85% of the calcium 3.6 mM response). Nifedipine produced a shift to the right of the concentration-effect curve for CGP 28392 without decreasing the maximum contractile response, suggesting competitive antagonism (pA2 = 8.3). Computer analysis of displacement of [3H]nitrendipine binding to intact heart cells by unlabeled CGP 28392 indicated a KD = 2.2 +/- 0.95 X 10(-7) M, in good agreement with the EC50 for the inotropic effect. CGP 28392 increased the rate of radioactive calcium influx (+39% at 10 seconds) without altering beating rate, while nifedipine decreased radioactive calcium influx and antagonized the CGP 28392-induced increase in calcium influx. Our results indicate that, in intact cultured myocytes, CGP 28392 acts as a calcium channel agonist and competes for the dihydropyridine-binding site of the slow calcium channel. In contrast to calcium channel blockers, CGP 28392 increases calcium influx and enhances the contractile state. PMID- 2581717 TI - A pharmacokinetic evaluation of IM administration of bleomycin oil suspension. AB - Bleomycin oil suspension was given IM twice daily to four patients, and bleomycin saline solution infused to three patients with cervical carcinoma. The serum levels of bleomycin were followed for 12 h by radioimmunoassay. Both regimens revealed comparable side effects. Only minor responses were seen. Bleomycin oil suspension produced prolonged levels of bleomycin in serum. PMID- 2581719 TI - Surface densities of diaphragmed fenestrae and transendothelial channels in different murine capillary beds. AB - Fenestrated capillaries are provided with two types of regular discontinuities: fenestrae with negatively charged diaphragms, and transendothelial channels fitted with two diaphragms, of which the luminal one is uncharged. These structures are expected to affect macromolecular exchanges on the basis of size and charge. We have detected variations in the surface density of fenestrations and transendothelial channels (normalized to 1 micron of capillary endothelial profiles in sections) in selected areas of different murine organs, i.e., kidney cortex, duodenal mucosa, and exocrine pancreas. The survey was limited to endothelial segments less than or equal to 400 nm thick, and covered a total length of endothelial profiles of 1180 microns, 730 microns, and 1189 microns in the exocrine pancreas, intestinal mucosa, and kidney cortex, respectively. At least 1000 transendothelial openings were recorded by scoring for easily recognizable fenestrations, transendothelial channels, and unknowns, the latter representing either of the above in grazing sections. The linear density of all transendothelial openings taken together was found to vary among the different capillary beds (kidney cortex greater than intestinal mucosa greater than exocrine pancreas). This same sequence was observed for the linear densities of fenestrations, transendothelial channels, and unknowns considered individually. The values obtained were as follows: kidney cortex, 1.35 fenestrations per micron, 0.25 transendothelial channels per micron, 0.52 unknowns per micron; intestinal mucosa, 0.92 fenestrations per micron, 0.10 transendothelial channels per micron, 0.38 unknowns per micron; exocrine pancreas, 0.58 fenestrations per micron, 0.04 transendothelial channels per micron, 0.27 unknowns per micron. The differences in distribution of transendothelial openings among fenestrated capillary beds probably reflect capillary permeability modulations connected with the functions of these various organs. PMID- 2581721 TI - Asthma and urticaria induced by seminal plasma in a woman with IgE antibody and T lymphocyte responsiveness to a seminal plasma antigen. AB - A patient with asthma urticaria and angioedema induced by allergy to seminal plasma was examined at intervals for 10 years. Before treatment her anaphylactic susceptibility to seminal plasma was manifested by very strong prick-test responses, IgE antibody to an allergenic fraction of seminal plasma determined by RAST, and by antigen-induced histamine release from her blood leucocytes. The skin test and in vitro lymphocyte tests indicated concomitant delayed hypersensitivity to the same allergen. The patient's lymphocytes treated with seminal plasma allergen fraction showed much increased incorporation of thymidine, and also synthesis of a product (NIF) that inhibited migration of neutrophils from a normal donor. The allergen fraction of seminal plasma had about five components in the range of 20 000-40 000 daltons molecular weight; the major fraction binding IgE appeared to be a glycoprotein. The patient was successfully desensitized by injections of her husband's seminal plasma. Desensitization was not associated with persistent amounts of antigen-specific IgG antibodies. PMID- 2581720 TI - The mechanism by which adenosine and cholinergic agents reduce contractility in rat myocardium. Correlation with cyclic adenosine monophosphate and receptor densities. AB - The adenosine analogue phenylisopropyladenosine decreased the basal and isoproterenol-stimulated contractile state of isolated rat left atria. The ED50 levels for both responses were similar, suggesting that direct and antiadrenergic effects may be mediated by the same receptor. Phenylisopropyladenosine decreased the cyclic adenosine monophosphate content of isolated atria and inhibited isoproterenol-stimulated adenylate cyclase activity in membranes prepared from atria and ventricles, but not as much as did methacholine. A maximally effective concentration of phenylisopropyladenosine or methacholine greatly reduced atrial contractility measured in the presence of either isoproterenol (1 microM) or Ro7 2956 (a phosphodiesterase inhibitor, 1 mM); however, in the presence of isoproterenol plus Ro7-2956, the contractile effects of phenylisopropyladenosine and methacholine were greatly attenuated. From the contractile data and cyclic adenosine monophosphate analyses, we conclude that direct and antiadrenergic contractile effects of both phenylisopropyladenosine and methacholine result primarily from their effects on cyclic adenosine monophosphate metabolism. The densities of adenosine, muscarinic, and beta-adrenergic receptors in rat atrial membranes were found to be 30, 551, and 24 fmol/mg protein, respectively, based on equilibrium-binding assays conducted with 125I-aminobenzyl-adenosine, [3H]quinuclidinyl benzilate, and 125I-labeled pindolol. The greater effectiveness of methacholine than phenylisopropyladenosine as a negative inotropic agent and an inhibitor of adenylate cyclase in atria may be related to the relative densities of muscarinic and adenosine receptors. PMID- 2581722 TI - Macroamylase not always evidenced by a broad band in agarose gel electrophoresis. PMID- 2581723 TI - Effect of dilution on amylase measurement with the Astra-8. PMID- 2581724 TI - Concentrations of protease and anti-protease in serum of patients with pancreatic cancer. AB - We measured the concentrations of trypsin, elastase, and three anti-proteases alpha 1-macroglobulin, alpha 1-antitrypsin, and alpha 1-antichymotrypsin-in serum from 10 patients with pancreatic carcinoma. All 10 showed increased elastase and decreased alpha 2-macroglobulin concentrations, nine had increased alpha 1 antichymotrypsin, and eight had increases in alpha 1-antitrypsin and trypsin. Serial studies during chemotherapy of one patient showed that the protease concentrations decreased during treatment but the concentrations of the anti proteases remained abnormal. PMID- 2581725 TI - Distribution of angiotensin converting enzyme in human tissues. AB - Angiotensin converting enzyme (EC 3.4.15.1, dipeptidyl carboxypeptidase, ACE, Kininase II), the peptidase which transforms inactive decapeptide, angiotensin I, to the pressor octapeptide, angiotensin II, and which catalyses also the degradation of vasodilative nonapeptide bradykinin, was measured in 27 human tissue homogenates and physiological fluids. Two assays were used: one which measures the hydrolysis of the substrate hippuryl-glycyl-glycine, by means of high performance liquid chromatography and another, using a colorimetric assay measuring the cleaved glycyl-glycine after arylation with picrylsulfonic acid. All the tissues studied contained measurable converting enzyme activities which were inhibited by captopril (SQ 14.225) in low concentrations. High specific activities of converting enzyme were found in several tissues of the intestinal and urogenital tract, but the highest activity was found in benign prostatic hyperplasia. Normal prostate and prostatic adenocarcinoma have a much lower activity. Results obtained for human tissues are compared with those found in animals. PMID- 2581726 TI - Amniotic fluid laminin and type IV collagen in normal and pathological pregnancies. AB - Specific radioimmunoassays for the fragment P1 of human laminin and the 7-S collagen domain of human type IV collagen were used to quantify these basement membrane proteins in second trimester amniotic fluid samples from 21 normal and 41 pathological pregnancies, the latter group being defined by elevated amniotic fluid alpha-foetoprotein (AFP) or abnormal foetal karyotype, or both. The mean laminin P1 concentration in the normal 15 to 18-wk pregnancies was 36 micrograms/l (range 10-77) and that of the 7-S collagen was 46 micrograms/l (range 7-152). The molecular size of the antigens in amniotic fluid from both normal and pathological pregnancies, when assessed by gel filtration was very large, probably representing intact laminin and type IV collagen. Pathological pregnancies, e.g. cases of Turner syndrome, Meckel syndrome and anencephaly often had elevated amniotic fluid laminin and type IV collagen concentrations. A weak, but nevertheless significant, correlation was found between the amniotic fluid laminin and type IV collagen concentrations and also between type IV collagen and AFP, but none between laminin and AFP. In eight pregnancies with foetuses suffering from the congenital nephrotic syndrome of the Finnish type, a genetic disease assumed primarily to involve some component of the glomerular basement membrane, the amniotic fluid concentrations of both laminin and type IV collagen were within normal limits in spite of an elevated amniotic fluid AFP. PMID- 2581727 TI - Preparation and characterization of monoclonal antibodies specific to placenta ferritin. AB - Ferritins are a group of isomeric proteins which function as the major iron storage protein of mammalian tissues. Some of the isoferritins have low isoelectric points, and are found in placenta and in malignant tissues and have therefore been termed carcinofetal ferritins. With the use of hybridoma technology, monoclonal antibodies (McAbs) specific to human placenta ferritin(s) were produced in order to characterize the heterogeneity of the molecule and to answer the question whether a specific antigenic determinant is associated with placenta and/or carcinofetal ferritin(s). Two McAbs designated H-9 and G-8 were developed. McAb H-9 bound specifically and exclusively to the ferritin isolated from human placenta, whereas G-8 McAb bound to placenta ferritin and cross reacted with ferritins isolated from human spleen and liver. No cross-reaction was observed between H-9 and G-8 reactive determinants. It was found further that the two antigenic determinants - the one recognized by G-8 and that recognized by H-9 McAbs - are molecularly associated on placenta ferritin. The results of this study led us to term the G-8 a 'common' ferritin antigenic determinant and H-9 a 'private' embryonic ferritin determinant. PMID- 2581728 TI - Evaluation of a new HDL2/HDL3 quantitation method based on precipitation with polyethylene glycol. PMID- 2581729 TI - Postnatal maturation of the islets of Langerhans in sheep. Light microscopic, immunohistochemical, morphometric, and ultrastructural investigations with particular reference to the transient appearance of argyrophil insulin immunoreactive cells. AB - The endocrine pancreas of lambs was found to offer an interesting animal model for some aspects of normal and pathological postnatal maturation of the islet parenchyma also in man. Normal features in lambs, previously observed in man, were the high volume density (5-8%) of the islet parenchyma, the high incidence of D (somatostatin) cells (about 30% even in young adult sheep), and the concentration of PP cells to the posterior part of the head of the pancreas. Particularly interesting was the presence in newborn lambs of large islet bodies (0.2-2 mm in diameter), consisting (to more than 90%) of large, argyrophil (Grimelius), granulated, parenchymal cells which were found to be insulin immunoreactive. Their secretion granules were smaller and more electron dense than those of the mature non-argyrophil B (insulin) cells. The argyrophil insulin immunoreactive cells often formed intercellular cavities and they could be equipped with microvilli and even cilia. At birth, these large islet bodies constituted more than half of the total islet parenchyma, but already during the first 10 days they underwent marked regressive changes (i.e. with large haemorrhages; "Blutinseln"); in 2-month-old lambs and in young adult sheep they had practically disappeared. These argyrophil insulin immunoreactive islet cells were considered to represent immature B cells with some persisting foetal characters. In 1- and 4-day-old lambs some non-argyrophil B cells in small islets of Langerhans harboured secretion granules of both types of B cells, indicating that a transformation could occur from 1 type to the other in this dual population of islet B cells. It was speculated that the argyrophil insulin immunoreactive cells could be homologues to the argyrophil islet cells often occurring in insulin-producing islet-cell neoplasms and in nesidiodysplasia in man. PMID- 2581730 TI - Defect of OKT4 antigen epitopes on normal human lymphocytes found in Japan. AB - Membrane surface antigens on peripheral blood lymphocytes were analyzed by a laser flow cytometry system using monoclonal antibodies. Four normal subjects among 1,998 normal and diseased groups were found whose lymphocytes were not detected by OKT4 monoclonal antibody, while Leu3a and KOLT-1, which were also specific for helper/inducer T-lymphocytes as OKT4, were present in these subjects. The cases with the defect of the OKT4 antigen suggest that there is some modification of the antigen, lack of epitopes, or genetic polymorphism in the appearance of the OKT4+ cell surface antigen on normal human lymphocyte. PMID- 2581731 TI - Genetic aspects of the spondyloarthropathies. AB - Family studies and investigation of the HLA associations have in recent years added to our understanding of the spondyloarthropathies. In regard to ankylosing spondylitis it is likely that B27 itself is the major susceptibility gene but that additional genes may play a secondary role. Heterogeneity of the B27 antigen has been demonstrated but has not yet been shown to be relevant to disease susceptibility. Haplotypes including Cw6 are related to susceptibility to psoriasis and psoriatic arthritis and although the risk for the arthropathy is increased in B27-positive individuals, there is some uncertainty regarding the association with other B locus antigens and further work is needed. There is also uncertainty as to whether B27-associated disorders occur randomly within families, or whether particular disorders cluster in certain families and further evidence in this field would be of considerable interest. Genetic studies, as here outlined, have not as yet had a major impact in clinical medicine but it is anticipated that a deeper understanding of the mechanisms of HLA-linked susceptibility genes and in particular of how they interact with environmental agents, will improve our ability to treat and possibly prevent the relevant diseases. PMID- 2581732 TI - Inflammatory bowel disease. AB - The place of inflammatory bowel disorders in the spondarthritis matrix has been discussed and aetiopathological and clinicoradiological features of their individual arthropathies described. Particular emphasis has been placed on the arthropathies of ulcerative colitis and Crohn's disease, but a comment is also included on the much rarer condition, Whipple's disease. The position of reactive arthritis resulting from enteric infection in relation to the spondarthritis concept is examined in the light of Reiter's-like clinical features and the association with HLA-B27. More 'peripheral' ideas of possible relevance to the spondarthritis idea (drug-induced colitis, intestinal-bypass syndrome) are included, together with a final section on experimental models of inflammatory bowel disease and of their arthropathies. It is concluded that certain inflammatory bowel disorders deserve a continuing place within the spondarthritis complex. Although their aetiopathogenesis is still imperfectly understood, it is likely that a blend of genes of small effect (polygenic inheritance) and environmental factors (e.g. microorganisms and/or their products) trigger disease processes which are enabled to manifest themselves by intermediary immunological processes. The precise way in which this is achieved is not yet known, but there is evidence that microorganisms (presumably in the gut of individuals genetically predisposed and suitably exposed environmentally) generate the formation of immune complexes. It is likely that these not only damage or further damage the mucosal lining of the bowel but also result in arthropathy and features of the disease 'distant' from bowel and joint (e.g. ocular inflammation, oral ulceration and skin manifestations). This concept is summarized in Figure 5. PMID- 2581733 TI - Effect of acclimation temperature on Km values towards GDP-mannose of the microsomal dolichol phosphate mannosyltransferase activity of trout liver (Salmo gairdnerii). AB - Apparent Km value for GDP-mannose remained stable when trout were raised and when enzyme activity was assayed at temps corresponding to the natural biological temp (between 5 and 15 degrees C). The Km value increased when the temperature of the assay was higher than 21 degrees C. Marked increase of the Km value was observed when trout were acclimated at 21 degrees C, whatever the temperature of the assay between 5 and 30 degrees C. PMID- 2581734 TI - Evolution of antibody structure and effector functions: comparative hemolytic activities of monomeric and tetrameric IgM from rainbow trout, Salmo gairdnerii. AB - Monomeric and tetrameric IgM anti-haptin antibodies isolated from the sera of rainbow trout (S. gairdnerii) by immunoaffinity chromatography were compared both immunochemically and with regard to their functional abilities to lyse haptenated trout erythrocytes in the presence of trout complement. The two populations had similar binding affinities for hapten and apparently identical L chains, but differed in H chain peptide maps and immunoreactivity with rabbit anti-trout H chain serum. These differences could not be attributed to J-chain. The abilities of the two antibody subpopulations to activate C to lyse haptenated trout erythrocytes also differed dramatically. Such functional differences are not simply explained by the greater avidity of the tetrameric form since preliminary studies show that the monomeric form of trout IgM activates C via an alternative pathway mechanism while the tetrameric form activates both classical and alternative pathway mechanisms. Results suggest divergent evolution of antibody structures involved in the familiar effector functions (C activation, transport, etc.). PMID- 2581736 TI - Allergy to mercurochrome and rifamycin. PMID- 2581735 TI - Metabolic activity of Trypanosoma lewisi cultured in vitro in the presence of normal or ablastinic rat serum. AB - Trypanosoma lewisi, in cultures supplemented with normal rat serum, synthesized the majority of new RNA during the first 13 hr of the culture, whereas DNA synthesis occurred from the 8th hr onwards and amino acids were incorporated into macromolecules uniformly throughout the 24 hr culture period. Thymidine was taken up by the parasite only between the 7th and 14th hr of culture, unlike uracil and amino acids which were taken up as required. Ablastin, a trypanostatic factor in the serum of infected rats, maximally inhibited DNA synthesis if it was added to the cultures before the 5th hr, partially inhibited synthesis if added between the 5th and 11th hr, but if added after this had no inhibitory effect. Ablastin only partially inhibited RNA synthesis and was without effect on amino acid utilisation. PMID- 2581738 TI - Vascular actions of VIP, substance P and neurotensin on the isolated perfused human fetal placenta. PMID- 2581737 TI - Stress hypokalemia. PMID- 2581739 TI - Structure and diversity of influenza virus neuraminidase. PMID- 2581740 TI - [Esophagus resection without thoracotomy in cancer. Report of experiences with 100 cases]. AB - Between 1980 and 1984 126 patients were admitted to the surgical department of the University of Dusseldorf for cancer of the esophagus. 100 (= 79%) patients were operated upon. In the majority of cases we dealt with advanced tumors (76% stage III and IV UICC). In 87 patients the esophagus was removed by transhiatal blunt dissection. In 13 patients the tumor bearing esophagus was bypassed by the substernally transferred stomach. Overall mortality was 20%. Varying with tumor stage the median time of survival was 5,5 months, again with wide variation depending of tumor stage. Only in stage I and II tumors there is a chance of significant prolongation of life or even cure. The majority of our patients and their relatives considered the outcome of the operation as a success, even if the time of survival was only short. PMID- 2581741 TI - [Colon anastomosis without suture and foreign material]. PMID- 2581742 TI - [Fluorescein angiography and its prognostic significance in central retinal vein occlusion]. PMID- 2581743 TI - The G0 in equilibrium G1 transitions of human lymphocytes as monitored by quantitative 14C-uridine autoradiography and high-resolution image analysis. AB - Human lymphocytes, transferred in culture into medium conditioned with phytohemagglutinin, were studied with the combined use of quantitative 14C uridine autoradiography and high-resolution image analysis. During the first 24 h before the onset of DNA synthesis it was possible to study pure G0 and G1 populations. The return of the proliferating cells into the G0 state was clearly monitored in an RNA synthesis rate/DNA content plot during 1-week growth. On days 3-6, the proliferation decreased progressively, and more cells accumulated in the quiescent G0 state. Geometric, densitometric, and textural parameters evaluated from the Feulgen-stained nuclei of the same cells indicated that the decondensation/condensation processes of the nuclear chromatin during the G0 in equilibrium G1 transitions paralleled the RNA synthesis activity. The results help to associate descriptors of nuclear morphology, as derived from image analysis, with functional parameters during activation and return to quiescence of human lymphocytes. PMID- 2581744 TI - Screening and prevention of colorectal cancer in Haining County. AB - From September 15, 1977, to April 15, 1978, 450, 477 persons over the age of 7 years were screened for schistosomiasis; a subgroup of 198,950 over 30 years were screened for colorectal cancer. Seventy-five malignant colorectal tumors were discovered in the latter group, a positive rate of 37.69 per 100,000 (seven were colonic cancers, 14 rectal cancers, 20 polyps with cancerous change, and 34 carcinoids). Of this group, 2701 had various types of polyps and 5242 had definitive diagnostic schistosomiasis. History, physical examination, and an occult blood test are simple, useful methods for detecting late colorectal cancer but are of no value in preventive screening of early cases. While digital rectal examination is an important, effective method of diagnosing rectal cancer, the positive rate is one tenth that of rectoscopy. It cannot be used for mass screening because the examining finger cannot tolerate such constant use and is too short to discover higher tumors. The sequence of colorectal cancerous change found in our center was from normal intestinal epithelium to tumorigenic polyps or colorectal ulcer, to polyps with anaplastic change, to polyps with local cancerous change, to adenocarcinoma. Cancer was seen more frequently in villous and adenomatous polyps; these are called precancerous stages of colorectal cancer. No relationship between schistosomiasis and colorectal cancer was found. PMID- 2581746 TI - Changes in serum pancreatic enzymes after hormonal stimulation in chronic pancreatitis. AB - Eighteen patients with chronic pancreatitis and 12 healthy controls were subjected to hormonal stimulation by continuous secretin plus cerulein intravenous infusion or a rapid injection of secretin. In both tests total serum amylase, lipase, and TLI (trypsin-like immunoreactive substances) levels were measured. Continuous intravenous infusion does not bring about changes in the serum levels of the enzymes studied; rapid injection of secretin, however, induces changes in the serum levels of TLI and lipase (but not amylase) which makes it possible to distinguish patients with chronic pancreatitis in its early stages from advanced chronic pancreatitis but is of doubtful value in distinguishing healthy subjects from those suffering with chronic pancreatitis. PMID- 2581745 TI - Effect of parenteral amino acids on human pancreatic exocrine secretion. AB - Parenteral administration of amino acids has been utilized for the nutritional support of patients with a variety of gastrointestinal disorders including protracted pancreatitis and pancreatic fistulae. However, the effect of parenteral amino acid administration alone on human pancreatic secretion has not been studied. We have studied the short-term effect of parenteral administration of amino acids on pancreatic exocrine secretion in seven healthy men. A double lumen tube was placed in the duodenum and polyethylene glycol was perfused into the proximal duodenum at the rate of 10 ml/min. A second double-lumen tube was placed in the stomach and bromsulfthalein was perfused into the cardia. Samples of duodenal contents were aspirated and gastric contents recovered during one hour of intravenous saline infusion followed by two hours of an amino acid mixture infusion. Hourly outputs of protein and pancreatic enzymes were determined, correcting for duodenogastric reflux based on concentrations of both markers in the samples. Despite an average increase of 72% in the plasma concentration of the infused amino acids, the outputs of protein, trypsin and amylase did not change significantly during amino acid infusion; the output of lipase decreased significantly during amino acid infusion. Two subjects were given intravenous secretin and cholecystokinin following amino acids; this resulted in increased outputs of protein, trypsin, and amylase in both. We conclude that the parenteral administration of amino acids to healthy young men does not stimulate pancreatic enzyme secretion as measured by the method using duodenal marker perfusion at the rate of 10 ml/min. PMID- 2581748 TI - The sequence of 16S rRNA from Mycoplasma strain PG50. AB - The DNA sequence of one of the 16S rRNA genes (cistron rrnA) of Mycoplasma strain PG50 was determined. It is 1523 bp long and has about 70% homology to the sequence of Escherichia coli 16S rRNA (rrnB). The G + C content of the sequence is 48% compared with 56% G + C in the E. coli sequence. The secondary structure is formed and it is determined that most of the differences between the two sequences are seen in stems while loops in the secondary structure are conserved. A detailed description of differences and similarities to known sequences and rRNA oligonucleotide catalogues is given, and this information is used to discuss functional properties and phylogenetic relations of mycoplasma 16S rRNA. PMID- 2581747 TI - Effects of antithyroid drug therapy on blood glucose, serum insulin, and insulin binding to red blood cells in hyperthyroid patients of different ages. AB - The mechanism of glucose intolerance in thyrotoxicosis was investigated in 119 patients with Graves's disease with careful consideration of the age-related deterioration of glucose tolerance. Before and after treatment of thyrotoxicosis with antithyroid drug, changes of blood glucose (BG) and serum immunoreactive insulin (IRI) in response to 50 g oral glucose tolerance test (OGTT) and insulin binding to red blood cell (RBC) were evaluated. In control subjects, the sigma IRI/sigma BG ratio after 50-g OGTT decreased progressively with age without significant change in absolute sigma IRI value, suggesting the occurrence of age related insulin resistance. Glucose intolerance was much more apparent in hyperthyroid patients because of age-related relative decrease of insulin secretion. Such a decrease of insulin secretion was not found in age-matched postgastrectomy patients with a similar degree of hyperglycemia, however. Maximal binding of labeled insulin and number of insulin receptors of RBC were decreased in old patients but binding affinity was unchanged. Elevation of BG was partially suppressed when serum thyroxine (T4) and triiodothyronine (T3) were reduced to moderately supernormal levels, whereas sigma BG, sigma IRI, sigma IRI/sigma BG ratio, and insulin binding to RBC were all returned to normal when normal serum thyroid hormone concentration was maintained. Our data indicate that insufficient insulin secretion and reduced insulin action at the target cell are responsible, at least in large part, for age-related glucose intolerance in hyperthyroid patients. PMID- 2581749 TI - [Action of phospholipases on calcium transport into synaptosomes: phosphatidic acid--Ca ionophore]. PMID- 2581751 TI - [Mechanism of action of ionophore A-23187 on the slow incoming current of the frog atrium]. PMID- 2581750 TI - [Calcium channel and the contraction of smooth muscle cells]. PMID- 2581752 TI - [Immunoreactive beta-lipotropin and endorphins are secreted by the isolated alimentary complex of rats]. PMID- 2581754 TI - [Blood sedimentation reaction in repeated dextran infusions in the therapy of cerebral infarct]. PMID- 2581753 TI - [Therapy of acute myocardial infarct]. PMID- 2581755 TI - Responses to paired onset stimuli: implications for the delayed evoked potentials in multiple sclerosis. AB - In multiple sclerosis (MS), demyelination is reported to be patchy and randomly distributed across the optic nerve, and a double peaked or broadened shape of the peaks of the pattern evoked potential would be expected. We tested quantitatively this hypothesis for our routinely recorded responses of MS patients. There was no significant broadening of the peak shape in the 75 prolonged latency responses. In order to simulate the patchy character of the affection of the optic nerve in MS, we tested 2 healthy subjects with a stimulus consisting of 2 presentations of a checkerboard pattern to different parts of the visual field, but with an adjustable onset asynchrony. It was found that, when the asynchrony was small (less than 40 msec) the second of the two stimuli did not contribute to the response. This suppression of the second response could be observed even when the second stimulus, by increasing its contrast, was made to evoke a much larger response than the first stimulus, when presented separately. Inhibition of the second response seems to explain the lack of wave shape alteration in the responses of MS patients, which would be expected on the basis of the patchy character of the demyelination. The responses from the fastest conducting fibres seem to determine the response, and inhibit the responses of the demyelinated fibres. From this, it can be concluded that a delayed response would be expected only in patients in whom a considerable number of the fibres of the optic nerve is affected by the demyelination. This seriously limits the sensitivity of the method for early diagnosis. PMID- 2581756 TI - Evoked potentials in patients with Huntington's disease and their offspring. II. Visual evoked potentials. AB - Visual evoked potentials (VEPs) to full-field and half-field stimulation were recorded in a large sample of patients with Huntington's disease (n = 36) and subjects at risk (first-order offspring, n = 55) using a checkerboard pattern reversal stimulus. Whereas a clear diminution of the amplitudes found confirmed earlier findings in patients with Huntington's disease, further alterations of VEP wave forms consisted in the absence of asymmetric hemisphere lateralization to half-field stimulation (i) and severe distortion with amplification of the early NPN/PNP complexes (ii). Considering at least two different abnormal parameters necessary to represent a reliable indicator of the disease, 24 patients (67%) and 14 (25%) of the persons at risk exhibited pathological results. In contrast, only 2 among 36 patients (5%) but 30 (55%) among the offspring exhibited normal results. The diagnostic and predictive value of the investigation of VEPs in Huntington's disease is discussed. PMID- 2581757 TI - The effect of age, sex and interstimulus interval on augmenting and reducing of occipital VEPs. AB - Three intensities of patterned and unpatterned flashes were used to elicit occipital visually evoked potentials (VEPs) from 4 groups of 15 subjects: boys and girls aged 7-9 years and boys and 15 girls aged 13-15 years. Interstimulus intervals (ISIs) of 1, 2 and 4 sec were used. Amplitude/intensity (A/I) slope was computed for each ISI and flash type condition and an estimate was made of the ability to differentiate patterned from unpatterned stimuli. The latter was inferred from coefficients of correlation which reflected the degree of similarity between VEP wave forms elicited by the two types of flashes. Responses of younger children attenuated to increasing stimulus intensity (negative A/I slope), while VEP amplitude of older subjects augmented to brighter flashes. VEP amplitude reduction may be the response of an immature brain to overstimulation. Amplitude reducing by 7-9-year-old children does not appear to be related to insufficient time between flashes for visual system recovery, since ISI did not differentially affect A/I slope of the younger and older subjects. Longer ISIs did, however, tend to produce more positive A/I slopes for all subjects, but only for patterned stimuli, suggesting that pattern detectors do not fully recover with ISIs of 1 and 2 sec. The visual system of young children was relatively less efficient than that of older children at differentiating patterned from unpatterned stimuli, indicating a differential sensitivity of pattern detectors as a function of age. Gender was not a factor in either magnitude of A/I slope or similarity of VEP wave forms. PMID- 2581758 TI - The effects of profound hypothermia on the cervical SEP in humans: evidence of dual generators. AB - Somatosensory evoked potentials recorded over Erb's point and the cervical spine (at C2 and C7) were studied in a series of children undergoing cardiopulmonary bypass surgery with hypothermia alone (n = 15) or profound hypothermia and complete circulatory arrest (n = 15). A bifid response was recorded at normothermia or mild degrees of hypothermia at both C7 (N12a, N13a) and C2 (N12b, N13b). The differential responses of these components to profound hypothermia and ischaemia suggest that N12a and N12b represent components of the same dorsal root/dorsal column travelling wave, while N13a and N13b reflect postsynaptic activities which are thought to be generated at the dorsal horn and cuneate nucleus, respectively. PMID- 2581759 TI - The 40 Hertz auditory event-related potential: normal values and effects of lesions. AB - A model of the 40 Hz auditory event-related potential (40 Hz AERP) was developed and evaluated in a group of normal subjects and two patient groups. The model views the 40 Hz AERP as a combination of the brain-stem auditory evoked potential (BAEP) and a sinusoidal component presumed to arise from structures rostral to the brain-stem. Fourier analysis techniques were used to quantify changes in the sinusoidal component. The results obtained demonstrated that the phase of the sinusoidal component was quite stable in normal subjects, but was predictably altered as a consequence of thalamic or midbrain lesions. Lesions of the temporal lobe did not alter the phase of the sinusoidal component. These results were interpreted as being consistent with the model developed and suggesting a midbrain or thalamic origin for the 40 Hz sinusoid. PMID- 2581760 TI - Scalp distributions of event-related potentials: an ambiguity associated with analysis of variance models. AB - Analysis of variance (ANOVA) interactions involving electrode location are often used to assess the statistical significance of differences between event-related potential (ERP) scalp distributions for different experimental conditions, subject groups, or ERP components. However, there is a fundamental incompatibility between the additive model upon which ANOVAs are based and the multiplicative effect on ERP voltages produced by differences in source strength. Using potential distributions generated by dipole sources in spherical volume conductor models, we demonstrate that highly significant interactions involving electrode location can be obtained between scalp distributions with identical shapes generated by the same source. Therefore, such interactions cannot be used as unambiguous indications of shape differences between distributions and hence of differences in source configuration. This ambiguity can be circumvented by scaling the data to eliminate overall amplitude differences between experimental conditions before an ANOVA is performed. Such analyses retain sensitivity to genuine differences in distributional shape, but do not confuse amplitude and shape differences. PMID- 2581761 TI - Cerebral potentials accompanying visually triggered finger movement in man. AB - The cerebral potentials associated with visually triggered movements of the right index finger were studied in 5 normal subjects using multichannel scalp recordings and separate stimulus and movement-locked averaging. The visually locked wave forms showed enhanced components of the passive visual evoked potential (P1-N1) with a more widespread distribution than the VEP. The amplitude of the P1-N1 complex was influenced by the reaction time but its timing was independent of the timing of the movement. In a 'move'/'no move' choice paradigm, the positive components following the P1-N1 complex were attenuated with movement and subtraction of the 'move' and 'no move' wave forms showed a movement-related negativity building up over the contralateral parietal and central regions. With movement-locked averaging, a pre-motor negativity (PMN) of comparable topography and timing to the readiness potential was found when the timing of the cuing stimulus was regular. With randomly timed stimuli, the PMN still developed but then plateaued prior to movement. It is suggested that in this situation the PMN is related to an increasing level of arousal, anticipation and preparedness to move which is then maintained pending the arrival of the stimulus and the final motor command. PMID- 2581762 TI - Cortical mapping of the auditory middle latency response in the unanesthetized guinea pig. AB - Auditory middle latency responses (MLRs) were mapped on the cortical surface of the unanesthetized guinea pig. The MLR consists of two positive peaks, designated A and C, with latencies of approximately 11 and 29 msec respectively, and a negative trough B, at 18 msec. Results suggest that each MLR component appears to have different generator sites and specific stimulus-response characteristics. The present work suggests that positive MLR components A and C have different generator sources because each component was maximally recorded from a different location over the contralateral temporal lobe. Little MLR activity was evident outside an area roughly 4 mm X 4 mm for each component. PMID- 2581763 TI - Aging changes in the cat P300 mimic the human. AB - Long-latency endogenous responses with characteristics of the human P300 were recorded from young cats (1-3 years). Principal components analysis and paired t tests confirmed that responses within a 200-300 msec latency window were significantly larger to rate stimuli than to frequent stimuli. In contrast, a similar study of long-latency responses in old cats (more than 10 years) showed no significant difference between the 'rare' and 'frequent' responses. These data indicate that the P300 changes functionally with old age in the cat, as in the human, and that the cat provides an important model for P300 generator analysis in the aged as well as in the young brain. PMID- 2581765 TI - Enzymatic reactions in organic solvents. PMID- 2581764 TI - [Changes in urinary levels of MHPG, VMA and 5-HIAA and plasma tryptophan in post partum blues. Initial results]. AB - In post-partum depressive illness ("post-partum blue") we measured urinary MHPG, VMA, 5-HIAA and free and total Trp. VMA and especially MHPG reflect the brain noradrenaline metabolism. Trp is the precursor of 5-HT synthesis and 5-HIAA is the main urinary catabolite of 5-HT. The clinical evaluation consisted in self evaluation scales: Pitt scale 1, 3 and 5 days after delivery, CESD scale of NIMH (depression) and BONIS scale (anxiety) at 6th day. Moreover a psychiatrist measured depression intensity on the MADRS scale and DSM III data. First results seem to indicate a decrease of free MHPG and VMA, an increase of 5-HIAA and no alteration of free and total Trp. These modifications could involve adrenergic and serotoninergic alterations in brain. PMID- 2581766 TI - Split genes. PMID- 2581767 TI - Strategies in pharmaceutical research. PMID- 2581768 TI - Hypothalamic hormones. PMID- 2581769 TI - Regulation of plasminogen activator production by bone-resorbing hormones in normal and malignant osteoblasts. AB - The plasminogen activator (PA) activity of clonal rat osteogenic sarcoma cell (phenotypically osteoblast) and of osteoblast-rich rat calvarial cells is shown to be increased by treatment with the bone-resorbing hormones, PTH, 1,25 dihydroxyvitamin D3, prostaglandin E2, and epidermal growth factor. Dose dependent increases were observed, after a lag period of 4 to 8 h. Stimulated and control PA activities were inhibited by actinomycin D and cycloheximide but not by cytosine arabinoside. Glucocorticoid hormones prevented the hormone stimulation, but other steroids did not. Calcitonin had no effect either on basal or on hormone-treated PA activity. Isobutyl-methylxanthine alone increased PA activity and enhanced responsiveness to PTH and to prostaglandin E2. These data point to a common pathway in the actions upon osteoblasts of several hormones with diverse initial cellular actions and raise the possibility that the PA/plasmin system may contribute to cellular mechanisms of bone turnover. PMID- 2581770 TI - Evidence that the [3H]estradiol-binding protein in pancreas is localized in exocrine cells. AB - Extracts of rat pancreas contain significant amounts of an [3H]estradiol-binding protein. The amount of steroid-binding activity that could be measured varied considerably depending on the tonicity of the homogenizing medium. High speed supernatants of homogenates initially prepared in isotonic buffer contained about 10% of the binding activity as homogenates prepared in hypotonic buffer. Extraction with hypotonic buffer of pellets obtained by the isotonic procedure yielded most of the remaining [3H]estradiol-binding activity. In an attempt to avoid errors resulting from incomplete homogenization and to detect possible changes in intracellular distribution of [3H]estradiol-binding activity, pancreata were initially homogenized in isotonic buffer and centrifuged at high speed (100,000 X g; 1 hr). The pellet was then extracted with hypotonic buffer and centrifuged again at high speed, and both supernatants were analyzed for [3H]estradiol-binding and amylase activities. Two or 14 days after treatment of male rats with streptozotocin, no apparent decline or redistribution of [3H]estradiol-binding activity to the cytosol was noted despite extensive alteration of beta-islet cells, as determined by electron microscopic examination of sections of these pancreata and significant loss of insulin, as measured by RIA. Amylase activity was unaffected 2 days after streptozotocin treatment, but was depressed to about 1% of control levels at 14 days. Administration of insulin to the latter group of animals resulted in return of amylase to normal levels and a modest increase (approximately 50%) in [3H]estradiol-binding activity. Since amylase levels remained unchanged 2 days after streptozotocin treatment, during which time beta-islet cells were irreversibly altered, and amylase activity was restored to normal levels by insulin treatment after its depletion in chronically treated animals, it follows that neither amylase nor the [3H]estradiol-binding protein could have been associated with beta-islet cells. This was consistent with the observation that M cells (a tumor line of beta-cells only) and 14B cells (a cloned variant of this insulinoma) had neither detectable amounts of amylase nor [3H]estradiol-binding activity. To determine whether estrogen-binding activity was associated with any other type of islet cell, islets of Langerhans were isolated by the sedimentation procedure of Lacy and Kostianovsky. In this procedure, several washing steps are employed to separate the suspended acinar cells from the denser islets that sediment rapidly. During this isolation procedure, the cells from each wash were analyzed for protein, [3H]estradiol binding protein, and amylase a PMID- 2581771 TI - Forskolin, an activator of adenylate cyclase, stimulates pancreatic insulin, glucagon, and somatostatin release in the dog: studies in vitro. AB - Forskolin, a direct activator of adenylate cyclase, stimulates cAMP production in islet cells. The effects of forskolin on the release of somatostatin, glucagon, and insulin were studied using the isolated, perfused dog pancreas. It was found that concentrations ranging from 0.075 microM-1 microM stimulated the secretion of somatostatin, glucagon, and insulin in a dose-related manner. The effects of 0.15 microM and of 0.6 microM forskolin were modulated by the prevailing glucose level with higher D and B and lower A cell responses at high (11 mM) than at low (2.8 mM) or zero glucose. In the absence of extracellular Ca++, forskolin (1 microM) possessed no stimulatory effect on pancreatic hormone secretion. Perfusion of 1 microM atropine, 1 microM propranolol, and 1 microM phentolamine had no effect on forskolin-mediated (0.3 microM) hormone output from pancreas. The phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (25 microM) elicited qualitatively similar hormone response to forskolin. In conclusion, the experiments demonstrate that forskolin is a potent, reversible, stimulus of pancreatic hormone secretion. Its effects are apparently not mediated via the sympathetic or parasympathetic nerve endings in pancreas. Forskolin may prove to be a valuable pharmacological tool in probing the role of the adenylate cyclase cAMP system in pancreatic hormone secretion. PMID- 2581772 TI - Bone cell phosphotyrosine phosphatase: characterization and regulation by calcitropic hormones. AB - Isolated bone cells in culture contain an enzyme capable of hydrolyzing the phosphate ester of phosphotyrosine. This enzyme, which we have termed phosphotyrosine phosphatase, has not previously been reported in bone. Some of its characteristics include: 1) maximum activity near physiological pH, 2) a Km for substrate of 52 microM, 3) marked inhibition by the phosphate analog vanadate ion, 4) activity correlation with bone cell alkaline phosphatase, and 5) regulation by bone target hormones. Data obtained with vanadate ion support the contention that this enzyme may play a role in the regulation of bone cell growth. PMID- 2581773 TI - Inhibition of viral interferon induction in mammalian cell cultures by azo dyes and derivatives activated with rat liver S9 fraction. AB - Four azo dyes (Benzopurpurine 4B, trypan blue, Direct Blue 15, and Congo red) and their derivatives (o-tolidine, o-dianisidine, and benzidine) were studied for their effect on induction of interferon by influenza virus in mammalian, Rhesus monkey kidney (LLC-MK2), cell monolayers. Whereas Benzopurpurine 4B, Direct Blue 15, and Congo red inhibited viral interferon induction from approximately 35 to 60%, negligible inhibition was noted with trypan blue and other derivative compounds. By comparison, when rat S9 fraction was used for enzymatic activation of azo dyes and derivatives, interferon inhibition was significantly depressed moreover (P less than 0.01 to less than 0.0001) by all chemical compounds. The concentration of rat S9 (0.5%) used for metabolic activation of dyes and congeners was critical because concentrations greater than 0.5% of S9 per se inhibited the interferon induction process. Uninduced hamster S9 and both Aroclor 1254-induced hamster and rat S9 fractions were all comparable in their ability to activate the chemical compounds tested. That potential mutagenic and carcinogenic chemicals which require metabolic activation can be discriminated on the basis of interferon induction inhibition in eukaryotic cell cultures augurs for the usefulness and credibility of this system. PMID- 2581774 TI - Influenza virus infection in mice after exposure to coal dust and diesel engine emissions. AB - Influenza virus infection initiated after aerosol exposure of CD-1, white Swiss mice for durations of 1, 3, and 6 months to respirable particulates maintained at 2 mg/m3 of either coal dust (CD), diesel engine emissions (DEE), a combination of both (CD/DEE), or to filtered air (control) was studied. The course of infection in mice previously exposed for 1 month to various particulates did not differ appreciably among the four animal groups with respect to mortality, virus growth in lungs, interferon levels, or hemagglutinin antibody response. In mice exposed for 3 and 6 months to different particulates, the mortality response was similar among all animal groups. However, the percentage of animals showing lung consolidation was significantly higher in the 3-month groups exposed to DEE (96.5%) and CD/DEE (97%) than in the control (61.2%); in the 6-month groups, the percentages were twice that of the control for both DEE- and CD/DEE-exposed animals. Complementing these observations of both 3- and 6-month-exposed animals was the higher virus growth levels attained in the DEE and CD/DEE animals with concomitant depressed interferon levels which were the inverse of findings noted in the control group. Hemagglutinin-antibody levels in particulate-exposed animals, especially at the 6-month interval, were fourfold less than the control. Histopathologic examination of lungs revealed no qualitative differences in the inflammatory response at any one specified time interval of exposure to influenza virus among the control and particulate-exposed animal groups. However, there were differences in severity of reaction in relation to the particulate component of the exposures. Focal macular collections of pigment-laden macrophages were seen only in DEE and CD/DEE but not in CD animals after 3- and 6-month exposures. The findings of this study indicated that the severity of influenza virus infection is more pronounced in mice exposed to diesel engine emissions than in control animals and it is not appreciably accentuated by coal dust. PMID- 2581775 TI - Biphasic increase in the in vivo phosphorylation of nuclear 110-kDa protein during early lymphocyte transformation. AB - A major 110-kDa phosphoprotein in rat liver and hepatoma (P 110) was identified in nuclear 0.2 M HCl extracts from rat lymph node cells. Stimulation with concanavalin A altered both the amount of P110 and, more strikingly, its in vivo phosphorylation in a typical biphasic manner with an initial maximum after 10-14 h. RNA synthesis showed a similar biphasic increase. Inhibition of hnRNA synthesis (5,6 dichlorobenzimidazoleriboside), but not of DNA synthesis (hydroxyurea), depressed both the amount of P110 and its phosphorylation markedly. PMID- 2581776 TI - Properties of a DNA repair endonuclease from mouse plasmacytoma cells. AB - The properties of a DNA-repair endonuclease isolated from mouse plasmacytoma cells have been further studied. It acted on ultraviolet-light-irradiated supercoiled DNA, and the requirement for a supercoiled substrate was absolute at ultraviolet light doses below 1.5 kJ m-2. At higher doses relaxed DNA could also serve as a substrate, but the activity on this DNA was due mostly to hydrolysis of ultraviolet-light-induced apurinic/apyrimidinic (AP) sites by the AP endonuclease activity associated with the enzyme. The latter enzyme activity did not require a supercoiled form of the DNA. The enzyme also introduced nicks in unirradiated d(A-T)n. The nicked ultraviolet-light-irradiated DNA served as a substrate for DNA polymerase I, showing that the nicks contained free 3'-OH ends. Treatment of the nicked ultraviolet-light-irradiated DNA with bacterial alkaline phosphatase followed by T4 polynucleotide kinase, resulted in the phosphorylation of the 5' ends of the nicks, indicating that the nicks possessed a 5'-phosphate group; 5'- and 3'-mononucleotide analyses of the labelled DNA suggested that the enzyme introduced breaks primarily between G and T residues. The enzyme did not act on any specific region on the supercoiled DNA molecule; it produced random nicks in ultraviolet-light-modified phi X 174 replicative form I DNA. Antibodies raised against ultraviolet-light-irradiated DNA inhibited the activity. DNA adducts such as N-acetoxy-2-acetylaminofluorene and psoralen were not recognized by the enzyme. It is suggested that the enzyme has a specificity directed toward helical distortions. PMID- 2581777 TI - Maturation of the 3' end of 5-S ribosomal RNA from Escherichia coli. AB - The 3' ends of 5-S rRNA isolated from Escherichia coli cells were analyzed and identified after different durations of labeling with 32Pi, with and without blocking of protein synthesis. These experiments suggest that the 5-S rRNA starts as a species containing 126 nucleotides, three at each end, and that the extra nucleotides are removed from the 5' and 3' ends in parallel at comparable but different rates. Inhibition of protein synthesis with chloramphenicol blocks, in addition to the 5'-end maturation, the trimming of the extra nucleotides from the 3' end. The trimming of extra nucleotides from both ends of the 5-S rRNA is also affected by the structure of the molecular stalk of 5-S rRNA. A number of observations suggest that the trimmings from both ends are independent processes, which are carried out probably by different enzymes. PMID- 2581778 TI - Limited proteolysis of human low-molecular-mass kininogen by tissue kallikrein. Isolation and characterization of the heavy and the light chains. AB - The limited proteolysis of human low-molecular-mass kininogen by kallikrein from tissue sources has been studied. Porcine pancreatic kallikrein applied in catalytic amounts split the kininogen molecule (apparent mass 68 kDa) with the release of lysyl-bradykinin (1 kDa). This generated a nicked kininogen molecule with a heavy chain and light chain interconnected via disulfide bridging. Following reductive cleavage of the disulfide bonds, the heavy chain of apparent mass 62 kDa was isolated by preparative sodium dodecyl sulfate electrophoresis, and the light chain of 5 kDa by reversed-phase high-performance liquid chromatography. The light chain was found to be composed of 38 amino acids with a single half-cystine residue. Amino-terminal sequence analysis revealed that the light chain is derived from the carboxy terminus of the kininogen molecule [Lottspeich et al. (1984) Eur. J. Biochem. 142, 227-232]. Immunological characterization of the isolated L chain indicated that it harbours antigenic site(s) unique for low-Mr kininogen as well as sites common to high-Mr and low-Mr kininogen. PMID- 2581779 TI - The design of fluorescent probes which bind to the active centre of guanidinobenzoatase. Application to the location of cells possessing this enzyme. AB - Cells possessing a known enzymic activity may be located by fluorescent probes designed to act as competitive inhibitors of this enzyme. We have prepared a series of dansyl N-substituted guanidino derivatives which bind to the active centre of guanidinobenzoatase. 9-Aminoacridine also acts as a competitive inhibitor and behaves similarly to these guanidino derivatives. These fluorescent probes have been used to locate tumour cells possessing this enzyme in thin sections of fixed tissue by employing fluorescent microscopy. PMID- 2581780 TI - Specificity of cGMP binding to a purified cGMP-stimulated phosphodiesterase from bovine adrenal tissue. AB - The binding of [3H]cGMP (guanosine 3',5'-monophosphate) to purified bovine adrenal cGMP-stimulated phosphodiesterase was measured by Millipore filtration on cellulose ester filter. [3H]cGMP-binding activity was enhanced when the assay was terminated in buffer containing 70% of saturated ammonium sulfate to dilute the enzyme and wash the filters. The cGMP-binding activity was co-purified with the phosphodiesterase activity. The binding of [3H]cGMP to purified enzyme was measured in the presence or absence of the phosphodiesterase inhibitor, 1-methyl 3-isobutylxanthine. 1-Methyl-3-isobutylxanthine showed linear competitive inhibition with respect to cGMP as substrate in the phosphodiesterase reaction but stimulated the [3H]cGMP-binding activity in the binding assay. The stimulatory effect appeared not to be the result of preservation from [3H]cGMP hydrolysis; no cGMP phosphodiesterase activity has been measured under the cGMP binding assay conditions, in the absence or presence of the inhibitor. Half maximal stimulation by 1-methyl-3-isobutylxanthine occurred in the 5-7 microM concentration range. The specificity of binding of [3H]cGMP was investigated by adding increasing concentration of unlabeled analogs of cAMP (adenosine 3',5' monophosphate) and cGMP. The binding of [3H]cGMP (50 nM) was displaced by unlabeled cGMP and cAMP with the following potency: 50% displacement was reached at the 0.1 microM cGMP range and only at a fiftyfold higher cAMP concentration. Our data with comparative series of analogs (e.g. 5'-amino-5'-deoxyguanosine 3',5'-monophosphate and 3'-amino-3'-deoxyguanosine 3',5'-monophosphate) showed that the potencies of stimulation of cAMP phosphodiesterase activity parallels displacement curves or [3H]cGMP binding to purified enzyme with no correlation with phosphodiesterase inhibition sequences. Those experiments suggest that the cGMP-binding activity is directly related to the non-catalytic (allosteric) cGMP binding site. PMID- 2581781 TI - Inclusion-cytology versus smear-cytology in fine needle abdominal biopsy. AB - 1568 patients underwent percutaneous fine needle biopsy (22-23 g. Chiba). 761 of these had histologic type confirmation of malignant disease. Among the latter, 313 cases had adequate samples retrieved from the same lesion for smear cytology (SC) and inclusion cytology (IC), 400 for SC alone (378 performed before the use of IC) and 48 for IC alone. SC was stained by Papanicolaou and MGG, IC by haematoxylin-eosin technique. In SC + IC group typing accuracy was 0.64 for SC and 0.86 for IC, in SC group was 0.66, in IC group was 0.87. IC permitted an easier preparation and interpretation of special stains. In conclusion, IC routine is recommended. Some interesting observations were possible because material was collected from three hospitals. PMID- 2581782 TI - Injected cyclic AMP increases ciliary beat frequency in conjunction with membrane hyperpolarization. AB - Injections of cyclic AMP (cAMP) and 8-Br-cAMP into Paramecium and external application of isobutylmethylxanthine (IBMX), an inhibitor of cAMP breakdown, to these cells increased the frequency of ciliary beating and hyperpolarized the membrane potential. When the membrane potential was held equal to the resting potential under voltage clamp, the same experimental conditions which serve to increase intracellular cAMP did not raise the ciliary frequency. We conclude that cAMP is presumably not the direct mediator of the hyperpolarization-induced ciliary activation, although it may be associated with this motor response. PMID- 2581783 TI - Homologies between paraflagellar rod proteins from trypanosomes and euglenoids revealed by a monoclonal antibody. AB - A Nonidet P 40 insoluble fraction was isolated from Trypanosoma brucei and was used to raise a monoclonal antibody (5E9). The antigen was localized by indirect immunofluorescence in the flagellum of T. brucei and of two species of euglenoids, Euglena gracilis and Distigma proteus. In immunoblot analysis, 5E9 appeared to bind to paraflagellar rod proteins PFR1 and PFR2 of T. brucei (72000 and 75000 mol. wt.) and of E. gracilis (67000 and 76000 mol. wt.). The presence of a common epitope in paraflagellar rod proteins from species of trypanosomes and euglenoids shows that despite distinct structures of the rods some identical domain exists in the proteins that could be involved in their supramolecular assembly into a similar organelle. The antigenic determinant defined by 5E9 was also shown to be present in a 87000 molecular weight polypeptide located in the proximal part of the flagellum of Crithidia oncopelti in which a paraflagellar rod is not detectable at the ultrastructural level. PMID- 2581784 TI - Morphometrical and immunocytochemical characterization of peri-insular and tele insular acinar cells in the rat pancreas. AB - Morphometrical and immunocytochemical techniques have been applied in order to characterize the pancreatic acinar cells located in peri-insular and tele-insular regions of the pancreas. The results obtained, have shown that the acinar cells of the peri-insular regions are twice as large as those of the tele-insular. On the other hand, the volume density of all organelles, except that of the zymogen granules, remains constant implying that the larger the cell, the larger are its organelles. For the zymogen granules however, their volume density was found to be higher in peri-insular acinar cells. The immunofluorescence technique applied for the demonstration of amylase and chymotrypsinogen has confirmed the presence of an inhomogeneity in the staining. Acinar cells in peri-insular regions show a brighter fluorescent staining. At the electron microscope level, both amylase and chymotrypsinogen were demonstrated in all organelles of acinar cells involved in protein secretion. Quantitative evaluations demonstrate no major differences in the intensity of labeling per micron2 between organelles of peri-insular and tele insular cells. These results put together demonstrate that peri-insular acinar cells contain higher amounts of secretory proteins because their organelles are larger and their zymogen granules are more numerous. The partition of the exocrine pancreas into peri- and tele-insular regions, confirmed herein through morphometrical and cytochemical techniques, is discussed in relation to the possible influence of the endocrine secretion arising from the islets of Langerhans on the surrounding acinar cells. PMID- 2581785 TI - Structural aspects of intranuclear matrix disintegration upon RNase digestion of HeLa cell nuclei. AB - The organization of the intranuclear elements observed in histone-depleted (2 M NaCl-extracted) HeLa cell nuclei was investigated by means of electron microscopy and two-dimensional gel electrophoresis. This work was mainly aimed at verifying whether or not an intranuclear skeleton or matrix existed, which could explain the stable attachment of RNA to the residual nuclear structure after high-salt extraction, and its three-dimensional organization. We compared the ultrastructure and the polypeptide composition of RNA-containing and RNA-depleted (RNase-treated) nuclear residues, and we visualized intermediate stages of RNase action on the intranuclear material. We showed that this material was made of two types (fibrillar and granular) of salt-resistant RNP components equally sensitive to RNase when the enzyme was used prior to high-salt extraction. At least in our material and under our experimental conditions, no intranuclear matrix could be distinguished from the residual RNP material. Our results further suggest that formation of such a matrix is a path-dependent phenomenon. PMID- 2581786 TI - Renal gammagraphy with 99mTc-phosphomycin. AB - 99mTc-Phosphomycin, a new radiopharmaceutical for kidney visualization, was used for animal experiments and tests of 171 patients. The results confirmed the usefulness of this product. The ease and yield of the labelling procedure, the low cost of the product, the excellent quality of the images and the functional information obtained showed that the use of 99mTc-phosphomycin as a radiopharmaceutical for kidney visualization has many advantages. PMID- 2581787 TI - Refsum's disease: management by diet and plasmapheresis. AB - A case of Refsum's disease treated by serial plasma exchanges together with a moderate low phytanate diet is reported. Serial plasma exchanges determined a rapid significant clinical improvement (neuropathy and cerebellar ataxia) that allowed immediate return to full-time employment. The initial improvement could be maintained by intermittent serial plasmapheresis despite partial failure of the initially introduced low phytanate diet bringing 20 mg phytanic acid daily. A new dietary regimen bringing 10 mg phytanic acid was later introduced that was well tolerated. No liquid formula was used. The clinical improvement was clearly correlated to a fall in serum phytanic acid from 45.3 to 16.2 mg/100 ml. PMID- 2581788 TI - Effect of aprotinin on metabolic changes in blood following aortofemoral bypass operation. AB - The effect of aprotinin on metabolic changes in blood of 23 patients undergoing Y graft aortofemoral bypass operation was studied before clamping and after declamping. The right femoral artery was clamped for 122 +/- 15 (-aprotinin) and 115 +/- 10 min (aprotinin group), the left femoral artery 129 +/- 27 (-aprotinin) and 159 +/- 25 min (aprotinin group), respectively. Aprotinin caused a significant decrease of blood lactate, pyruvate, citrate and oxoglutarate levels compared with untreated controls, whereas acetoacetate and beta-hydroxybutyrate concentrations were significantly increased. It is hypothesized that blood lactate and pyruvate levels are lowered due to increased pyruvate oxidation. Limitation of citrate synthesis due to lack of oxaloacetate might explain subsequent formation of ketone bodies. PMID- 2581789 TI - Analysis of autoreactive I region-restricted T cell colonies isolated from the guinea pig syngeneic mixed leukocyte reaction and from immune responses to conventional foreign antigens. AB - Guinea pig proliferating T cell colonies were isolated from T cell populations stimulated during the syngeneic mixed leukocyte reaction (SMLR) or following positive selection of immune T lymphocytes specific for pork insulin (PI) or the copolymer of L-glutamic acid, L-lysine (GL). SMLR-responding T cell colonies could be isolated in the absence of any extrinsic antigen and were strictly restricted to the recognition of Ia molecules on stimulator peritoneal exudate cells (PEC) and required both stimulator cells and interleukin 2-enriched fluids for optimal proliferative responses. Blocking of T cell colony proliferation with a panel of monoclonal anti-Ia antibodies showed that SMLR T cell colonies were restricted by discrete and distinct self-Ia epitopes. Analysis of individual T cell colonies generated against PI and GL revealed three types of colonies: (a) antigen specific, I region-restricted; (b) autoreactive, I region-restricted; and (c) antigen specific, but also autoreactive. These doubly reactive colonies were restricted to the same Ia epitope when stimulated with self-PEC alone or when stimulated with self-PEC in the presence of the relevant exogenous antigen. These results substantiate the hypothesis that both the SMLR and antigen-specific responses are mediated by a common set of precursor T lymphocytes and that the guinea pig SMLR is at least in part the result of the polyclonal proliferative responses of several distinct antigen-reactive T cell clones in the absence of exogenous antigen. PMID- 2581790 TI - Production and characterization of monoclonal anti-Thy-1 antibodies that stimulate lymphokine production by cytolytic T cell clones. AB - In an effort to derive monoclonal antibodies (mAb) which can induce production of macrophage-activating factor (MAF) by cloned murine cytolytic T lymphocyte (CTL) lines, we have fused spleen cells from a rat immunized with a CTL clone with the nonsecreting mouse myeloma X63-Ag8.653. Three mAb (designated I-22, III-5 and V 8) were found to stimulate MAF production by the immunizing CTL clone and (with a single exception) two other unrelated CTL clones. However, none of these mAb inhibited the cytolytic activity of the clones. Immunoprecipitation studies indicated that the three mAb reacted primarily with a 25-30-kDa protein which could not be distinguished from that precipitated by either a reference anti-Thy 1.2 mAb or a polyclonal rabbit anti-Thy-1 antiserum. Moreover, competition binding experiments demonstrated that the three mAb competed with each other and with the reference anti-Thy-1.2 mAb. Flow cytofluorometric analysis of the strain distribution of the molecules defined by the mAb revealed that two of the antibodies (I-22 and III-5) were directed against nonpolymorphic determinants of Thy-1, whereas V-8 mAb reacted only with Thy-1.2+ lymphocytes. One of the mAb (III-5) was also able to stimulate proliferation and interleukin 2 secretion by normal splenic T cells. Since mAb directed against a number of other surface structures on CTL clones did not stimulate MAF production, it thus appears that Thy-1 (or molecules associated with Thy-1) may play a functional role in T lymphocyte triggering. PMID- 2581791 TI - Splenic dependence of the antibody response to thymus-independent (TI-2) antigens. AB - The murine antibody response to T-independent (TI)-2 antigens [2,4-dinitrophenyl Lys-Ficoll (DNP-FIC) and DNP-hydroxyethyl starch (HES)] was impaired long after splenectomy, while responses to TI-1 [trinitrophenylated lipopolysaccharide (TNP LPS)] and thymus-dependent [TNP-keyhole limpet hemocyanin (KLH)] antigens were largely unaffected. The antibody response to these TI-2 antigens was exclusively against the conjugated epitopes [DNP-, fluorescein isothiocyanate (FITC)- or tetramethylrhodamine isothiocyanate (TRITC)-Ficoll or -HES]. Fluorescent conjugates of Ficoll and HES localize selectively to the splenic marginal zone macrophages. This localization was not affected by 750 cGy of X-irradiation, but the antibody response to the TI-2 antigens was abrogated for 14 days. Administration of spleen cells restored the antibody response to these TI-2 antigens in otherwise intact irradiated mice but not if they had been splenectomized. Our findings indicate that the antibody response to TI-2 antigens depends upon stimulation of B cells in a splenic environment. This probably involves antigen presentation by marginal zone macrophages. PMID- 2581792 TI - Regulation of Epstein-Barr virus infection by recombinant interferons. Selected sensitivity to interferon-gamma. AB - Interferons (IFN) are antiviral proteins that may be important in mediating cellular defenses against Epstein-Barr virus (EBV) infection. However, the means by which IFN-alpha, -beta and -gamma modify EBV infectivity are not clear. We have evaluated the effects of purified recombinant preparations of all three classes of IFN on EBV-induced B lymphocyte proliferation and Ig secretion. When added early after EBV infection, all three recombinant IFN reduced B cell outgrowth and Ig secretion. IFN-gamma exerted a 7-10-fold more potent antiviral effect than IFN-alpha or -beta. All three types of IFN act directly on B cells. Monocytes and natural killer cells are not necessary for the anti-EBV activity. Of the three recombinant IFN, only IFN-gamma reduced EBV-induced proliferation and Ig secretion when added 3-4 days after virus infection; IFN-alpha/beta were only effective up to 24 h. B lymphoblastoid lines already transformed by EBV are insensitive to the anti-proliferative actions of all three types of IFN. On the basis of these findings, we propose three phases of regulation during EBV infection. In the early phase, EBV-infected cells can be regulated by all IFN. Subsequently, there is an intermediate period where only IFN-gamma is capable of directly affecting EBV-induced B cell responses. In the third phase, B lymphocytes become insensitive to direct actions of all IFN and are now subject to regulation only by cytotoxic cells. PMID- 2581793 TI - Substance P antagonists showing some selectivity for different receptor types. AB - Five antagonists have been used against substance P (SP) and neurokinin A (NA) in isolated smooth muscle preparations containing either SP-P (the guinea pig ileum (G.P.I.), the dog carotid artery (D.C.A.) or SP-E receptors (the rat duodenum (R.D.), the dog (D.U.B.) and hamster urinary bladders (H.U.B.]. [D-Pro4,D Trp7,9,10, Phe11]SP-(4-11) was found to be selective for SP-P receptors, since it showed high affinity both against SP and NA, on the G.P.I. and D.C.A., while it was found to be inactive on some SP-E receptor systems (D.U.B., H.U.B.) and very weak in others (R.D.). Two octapeptide antagonists, modified in position 6, [D Pro4,Ala6,D-Trp7,9,10,Phe11]SP-(4-11) and [D-Pro4,Lys6,D-Trp7,9,10,Phe11]SP-(4 11) showed some selectivity for SP-E receptors since they acted as full agonists on one SP-P preparation (the D.C.A.) and the first compound contracted also the G.P.I. In addition to being pure antagonists on the D.U.B., H.U.B. and on the R.D., the two octapeptides showed a higher potency against the SP-E stimulant NA, compared to SP, in the R.D. Two undecapeptide antagonists were active against SP and NA on both SP-P and SP-E receptor preparations and therefore were less discriminative than the octapeptides. They were however more active against NA on the R.D., similar to the octapeptides modified in position 6. It is concluded that: (a) both agonists and antagonists appear to be useful for the characterization of tachykinins receptors; (b) either the whole N-terminal portion of SP or a shorter sequence, modified in position 6, increase the antagonist affinity against NA in the SP-E receptor system of the rat duodenum. PMID- 2581794 TI - Role of the dopamine uptake carrier in the neurochemical response to methamphetamine: effects of amfonelic acid. AB - Repeated administration of large doses of methamphetamine depresses both neostriatal tyrosine hydroxylase and tryptophan hydroxylase activity. Neostriatal concentrations of dopamine, serotonin and their acidic metabolites are similarly reduced by methamphetamine. Coadministration of the dopamine uptake inhibitor, amfonelic acid, selectively prevented the methamphetamine-induced decrease in tyrosine hydroxylase activity while not altering the depression of tryptophan hydroxylase activity. In vitro, amfonelic acid blocked methamphetamine-induced [3H]dopamine release from neostriatal slices but had no effect on [3H]serotonin release. In experiments conducted with [3H]amphetamine and amfonelic acid, no evidence was found for carrier-mediated transport of amphetamine. The results demonstrate a role for the dopamine uptake carrier in the neurochemical effects of high doses of methamphetamine. Furthermore, the ability of amfonelic acid to antagonize the neurochemical effects of methamphetamine appears to be due to an inhibition of carrier-mediated dopamine efflux rather than carrier-mediated uptake of methamphetamine. PMID- 2581795 TI - HVJ-induced fusion of liposome to erythrocyte. Possible involvement of virus induced activated state of erythrocyte membranes during fusion process. AB - HVJ-induced fusion between liposomes and erythrocytes was examined as a model of cell-cell fusion and the following results were obtained: Liposome-liposome fusion seldom occurred in the presence of HVJ. Liposomes free of receptors for viral HN protein could efficiently fuse with erythrocytes when the concentration of liposomes and erythrocytes was high. Direct interaction between HVJ and liposomes should be negligible in the present system. A distinct lag phase (10 min) was observed before the liposome-erythrocyte fusion occurred appreciably. Efficiency of the liposome-erythrocyte fusion decreased linearly up to 1 h after stopping the virus-erythrocyte fusion. The former fusion was almost negligible after 1 h but could be restored by further addition of HVJ. Efficiency of the liposome-erythrocyte fusion was suppressed significantly when erythrocytes were pretreated with N-ethylmaleimide (N-EM), a membrane-permeable sulfhydryl agent, whereas rho-chloromercuriphenylsulfonic acid (PCMBS), a membrane-impermeable sulfhydryl agent, had no appreciable effect on the fusion efficiency. The study suggests possible involvement of some HVJ-induced 'activated state' of the erythrocyte membrane during the process inducing the liposome-erythrocyte fusion. The structure including the membrane skeleton system may be responsible for producing an 'activated state' in the erythrocyte membrane. Such an 'activated state' was induced 10 min after the viral infection to erythrocytes, and thereafter decayed gradually. PMID- 2581796 TI - Reorganization of plasma membrane-associated 36 000 dalton protein upon drug induced redistribution of cytokeratin. AB - Epithelial PtK2 cells were used as a model to study the possible redistribution of the major tyrosine protein kinase substrate, p36, upon drug-induced reorganization of the cytokeratin network. Cells were grown on glass coverslips and exposed to cytochalasin D (CD), colcemid or a combination of the two. The cytokeratin type intermediate filaments of the cells were redistributed by treatment of the cells with colchicine and CD. Simultaneous changes in cytokeratin and in p36 antigen were observed by double-label immunofluorescence. In control PtK2 cells, p36 was distributed characteristically at the cortical cytoplasm. Neither colchicine nor CD alone was able to cause a major reorganization of cytokeratin or p36. Their combined effect resulted in formation of blebs containing abundant p36 at the cell surface and at cell-cell junctions. Actin, on the other hand, was reorganized to similar configurations by CD alone. These observations show for the first time a drug-induced redistribution of p36. The results suggest a relationship between membrane-associated p36 and the cytoskeletal fibres that terminate at the plasma membrane. PMID- 2581797 TI - mRNA usage during Drosophila melanogaster embryonic development. Analysis of nine cloned DNA segments. AB - A set of nine phage lambda clones containing inserts from Drosophila melanogaster which are complementary to cDNA made from oocyte poly(A)+ RNA were selected from a larger group. These cloned elements code for a range of middle abundant RNA sequences which show no appreciable change in abundance during Drosophila embryogenesis. Seven of the nine clones are complementary to two oocyte RNAs, one to three RNAs and one to four RNAs. This study describes the changes that occur in these RNAs during embryonic development in the polysomal and non-polysomal fraction, and in the poly(A)+ RNA and poly(A)- RNA fraction. In all nine of these clones, greater than 70% of the complementary RNA is found in the polysomal region of a sucrose gradient. This proportion increases somewhat during development. Specific changes have been found during development in the proportion of RNA that is poly(A)+. Depending to the cloned sequence, this proportion may increase, decrease, or remain unchanged. For those clones that show a change, most of this change occurs between 8 and 19 h of development. Our data suggest, furthermore, the presence of a class of non-adenylated RNA being utilized during embryogenesis. PMID- 2581798 TI - In vivo DNA synthesis in the dietary restricted long-lived rat. AB - Male CFY Sprague-Dawley rats maintained at 50% growth rate of ad libitum fed, age matched control animals showed a 42% extension in maximum lifespan and an increase in the overall doubling time of the rate of mortality from 102 days to 203 days. The slower growth rate of animals on the restricted diet was reflected in lower DNA, RNA, and protein content of liver, kidney and heart with age. DNA synthesis in vivo measured by the incorporation of 3H-thymidine was severely inhibited in liver, kidney, heart, and abdominal skin, particularly during the first six months of life. The developmental peak in DNA synthesis observed in liver and kidney of ad libitum fed animals before 100 days of age was completely inhibited. No effect of restricted feeding on DNA synthesis in the small intestine was observed; however, DNA synthesis was higher in thymic tissue from the experimental animals. A decrease in RNA content of liver, kidney, and heart preceded any change in protein or DNA in animals subjected to restricted feeding. The capacity for protein synthesis (RNA/DNA ratio) was decreased by restricted feeding and was associated with a reduced protein/DNA ratio indicative of reduced cell size during the first six months of life. The translational activity per ribosome (protein/RNA ratio) was not disturbed by undernutrition in any of the tissues studied. PMID- 2581800 TI - Caenorhabditis elegans: purification of isocitrate lyase and the isolation and cell-free translation of poly(A+)RNA. AB - Isocitrate lyase (EC 4.1.3.1) from mixed larval populations of Caenorhabditis elegans was stabilized in crude extracts by centrifugation over a 0.2-0.6 M sucrose gradient for 2.5 hr in a vertical rotor (VTi 50) at 210,000g. The peak fractions from this sucrose gradient showed a half-life of 33 hr at 30 C and 225 hr at 4 C in contrast to 2.5 and 52 hr, respectively, for the crude extract. A purification scheme involving (NH4)2SO4 precipitation and chromatography on Sepharose 6B and diethylaminoethyl-cellulose yielded isocitrate lyase that gave one band after electrophoresis in a sodium dodecyl sulfate-gel polymerized from 12% acrylamide. The purified enzyme with a molecular weight of 250,000 and subunit molecular weight of 61,600, had a specific activity of 2 mumoles glyoxylate formed min-1 mg protein-1, and was obtained in a 4% yield. Isocitrate lyase from C. elegans lost 80-85% of its activity in the precipitation by 33-55% (NH4)2SO4, but this step appeared to be necessary for purification to homogeneity. The use of fast protein liquid chromatography appeared to be promising in that it provided an enzyme preparation that was about 50% pure with a specific activity as high as 3 mumoles glyoxylate formed min-1 mg protein-1. Poly(A+)RNA was isolated from C. elegans and translated in wheat germ cell-free system. Analysis on a 10% sodium dodecyl sulfate-polyacrylamide gel showed varied translation products including one or more 60,000-Da polypeptides. PMID- 2581799 TI - Control of locomotion in marine mollusc Clione limacina. III. On the origin of locomotory rhythm. AB - Neurons from the isolated pedal ganglia of the marine mollusc Clione limacina were recorded from intracellularly during generation of the locomotory rhythm. Polarization of single type 7 or type 8 interneurons (which discharge in the D- and V-phases of a swim cycle, respectively) strongly affected activity of the rhythm generator. Injection of depolarizing and hyperpolarizing current usually resulted in shortening and lengthening of a swim cycle, respectively. A short pulse of hyperpolarizing current shifted the phase of the rhythmic generator. The same effect could be evoked by polarization of efferent neurons of types 2, 3 and 4 which are electrically coupled to interneurons. On the contrary, polarization of types 1, 6 and 10 efferent neurons, having no electrical connections with interneurons, did not affect the locomotory rhythm. A number of observations indicate that type 7 and 8 interneurons constitute the main source of postsynaptic potentials that were observed in all the "rhythmic" neurons of the pedal ganglia. Type 7 interneurons excited the D-phase neurons and inhibited the V-phase neurons; type 8 interneurons produced opposite effects. Tetrodotoxin eliminated spike generation in all efferent neurons of the pedal ganglia, while in interneurons spike generation persisted. After blocking the spike discharges in all the efferent neurons, type 7 and 8 interneurons were capable of generating alternating activity. One may conclude that these interneurons determine the main features of the swim pattern, i.e., the rhythmic alternating activity of two (D and V) populations of neurons. Both type 7 and type 8 interneurons were capable of endogenous rhythmic discharges with a period like that in normal swimming. This was demonstrated in experiments in which one of the two populations of "rhythmic" neurons (D or V) was inhibited by means of strong electrical hyperpolarization, as well as in experiments in which interaction between the two populations, mediated by chemical synapses, was blocked by Co2+ ions. Type 7 and 8 interneurons were capable of "rebound", i.e. they had a tendency to discharge after termination of inhibition. V-phase neurons exerted not only inhibitory but also excitatory action upon D-phase neurons, the excitatory action being longer than the inhibitory one. The main experimental findings correspond well to the model of rhythm generator consisting of two half-centres possessing endogenous rhythmic activity. The half-centres exert strong, short duration inhibitory and weak long duration excitatory actions upon one another. The behaviour of such a model is considered and compared with that of the locomotor generator of Clione. PMID- 2581801 TI - Trichinella spiralis: immunization of mice using monoclonal antibody affinity isolated antigens. AB - An antigen epitope was identified from the excretory-secretory products of Trichinella spiralis first-stage larvae using monoclonal antibodies, and the glycoprotein antigens bearing this epitope (Ts.49 and Ts.53) were isolated from the crude excretory-secretory preparation by affinity chromatography. In immunization experiments carried out in mice, antigen priming with Ts.49 and Ts.53 resulted in a reduction of muscle larvae resulting from a challenge infection at a level comparable to priming with crude excretory-secretory antigens. In addition, antigens Ts.49 and Ts.53 induced an accelerated expulsion of adult worms from the intestines of immunized mice and reduced the fecundity of remaining female worms. PMID- 2581803 TI - The effect of cyclic AMP on Na+ and K+ transport systems in mouse macrophages. AB - Exogenous cyclic AMP (cAMP) inhibits the Na+, K+-cotransport system and stimulates the Na+, K+-pump and Na+, Ca2+ exchange in mouse macrophages. These effects are enhanced by inhibition of phosphodiesterase with methylisobutylxanthine (MIX). MIX alone showed little or no effect. A similar response was observed after stimulation of endogenous production of cAMP by isoproterenol. PMID- 2581804 TI - Efficient cell proliferation and predominant accumulation of epsilon-globin mRNA in human leukemic K562 cells which produce mostly Hb Gower 1. AB - Long-term cultures of K562(S) cells in 50-75 microM hemin allow the selection of 'hemin-resistant' K562 cells together with cells which proliferate efficiently while fully induced to express the human embryonic globin genes, as the hemoglobin Gower 1 (zeta 2 epsilon 2) is the predominant hemoglobin produced. Our experiments demonstrate that these K562 cells accumulate mostly epsilon-globin mRNA (epsilon-globin mRNA/gamma-globin mRNA = 2.9) suggesting that the control of hemoglobin expression is at a pretranslational level. PMID- 2581802 TI - Changes of the level of proteinase inhibitors in rat plasma during turpentine induced inflammation. AB - The levels of rat plasma alpha-macroglobulins, alpha-cysteine proteinase inhibitor, haptoglobin and antipapain activity were studied during the acute phase reaction after an injection of alpha-pinen. An increase in concentration of all the compounds examined was observed. PMID- 2581805 TI - Genetic differences between inbred strains of mice; a new source of variation in high-sulphur keratins. AB - Proteins were extracted by improved techniques from the hair of inbred strains of Peru, C57BL/6 and CBA/Ca mice. The extracts were characterized by amino acid analysis and high resolution polyacrylamide gel electrophoresis, and previously unreported strain differences were observed. Genetic analysis confirmed them. PMID- 2581806 TI - Pseudomonas lectin PA-I detects hybrid product of blood group AB genes in saliva. AB - Pseudomonas aeruginosa galactophilic lectin PA-I exhibits an outstanding affinity for soluble hybrid oligosaccharide products of human A and B genes in saliva of heterozygous AB individuals. Neither A nor B salivas, nor an artificial mixture of them, inhibit PA-I hemagglutinating activity to the same extent as saliva from heterozygotes. Other lectins examined do not exhibit this property. PMID- 2581807 TI - Histamine H2 receptor activity during the differentiation of the human monocytic like cell line U-937. Comparison with prostaglandins and isoproterenol. AB - Histamine H2 receptor activity (cAMP generation) has been characterized in U-937 cells before and after retinoic acid-induced differentiation into monocyte /macrophage-like cells. The differentiation is associated with a decreased capacity of U-937 monocytes to generate cAMP under basal conditions or after cell surface receptor stimulation by histamine, isoproterenol and PGE1. In contrast, the potencies of the hormones are unchanged during monocytic maturation (EC50 values = 3.2-4.6 X 10(-6) M histamine, 4.6-7 X 10(-9) M isoproterenol, 2-4.6 X 10(-6) M PGE1). The data support the view that histamine and cAMP-inducing agents may control the proliferation and differentiation of normal and leukemic cells committed to monocytic maturation in man. They also raise the possibility that normal human monocytes also possess functional H2 receptors and that histamine may be implicated in the regulation of monocyte/macrophage functions. PMID- 2581808 TI - A low-Mr chemoattractant for vascular endothelial cells. AB - The formation of new blood vessels occurs by sprouting from previously existing microvasculature. The process involved directed migration of the vascular endothelial cells towards chemical signals released from the target tissue. We have used the Boyden chemotaxis chamber method to identify chemotactic signals for fetal bovine vascular endothelial cells. Human placenta organ cultures produce a high-Mr chemoattractant for the endothelial cells from which a low-Mr factor can be liberated with trichloroacetic acid treatment and ethanol extraction. This activity was isolated from extracts of human placenta using Sephadex LH-20, Amberlite XAD-2, and silica gel thin-layer chromatography. The Mr of the factor is less than 400, it is lipophilic and resistant to proteolytic enzymes. The factor induces chemotactic migration of both aortic endothelial cells and capillary endothelial cells from the retina, but has no effect on fibroblasts or leukocytes suggesting a specific function of the compound for the vascular endothelial cells. PMID- 2581809 TI - Reversible acetaldehyde inhibition of A23187-stimulated amylase secretion from isolated rat pancreatic acini. AB - The Ca2+ ionophore, A23187, stimulated amylase secretion from isolated rat pancreatic acini in a dose-dependent manner with a maximal effect at 6 microM. Acetaldehyde, a metabolite of ethanol, caused a reduction in the magnitude of ionophore-stimulated secretion with no evidence of competitive inhibition. Furthermore, 6 microM ionophore-stimulated amylase secretion was dose-dependently inhibited by acetaldehyde. This inhibitory effect of acetaldehyde, however, was reversible on washing and reincubating acetaldehyde-treated acini. These results suggest that acetaldehyde reversibly inhibits intracellular components mediating stimulated secretion and this inhibition requires a continuous chemical interaction between acetaldehyde and intracellular component(s) regulating stimulated enzyme secretion. PMID- 2581811 TI - Isolation of gram quantities of isoleucyl-tRNA synthetase from an overproducing strain of Escherichia coli and its use for purification of cognate tRNA. AB - The ileS gene coding for isoleucyl-tRNA synthetase was cloned on a runaway replication plasmid. From the cells harboring the plasmid, gram quantities of the synthetase were isolated using two column procedures. The synthetase was used for the purification of cognate tRNA. Isoleucine tRNAGAU of greater than 90% purity was easily isolated by taking advantage of a specific complex formation of the synthetase with cognate tRNA. PMID- 2581810 TI - Affinity of protein HU for different nucleic acids. AB - The binding of protein HU from Escherichia coli to nucleic acids was investigated by affinity chromatography under various conditions, by a nitrocellulose retention assay and by isopycnic centrifugations in metrizamide gradients. The results indicate that HU has a preference for binding to RNA and single-stranded DNA over double-stranded DNA. The affinity of HU for supercoiled DNA was also less than that of the corresponding relaxed DNA. PMID- 2581812 TI - Isolation and structure elucidation of an alpha-amylase inhibitor, AI-3688, from Streptomyces aureofaciens. AB - A novel polypeptide inhibitor, AI-3688, which acts upon human pancreatic alpha amylase, was isolated from fermentation broth of Streptomyces aureofaciens. The purified peptide contains no unusual amino acids. Its Mr is 3936. The primary structure of AI-3688 was elucidated by automatic Edman degradation of the native or modified inhibitor. Two intramolecular cysteines form a disulphide bridge, thus creating a ring structure consisting of 17 amino acids. Strong sequence homology also exists to another microbial alpha-amylase inhibitor, tendamistat (HOE 467). This paper discusses the role of a common partial sequence, -Gln-Ser Trp-Arg-Tyr-, present in the loop of both inhibitors as the active site of microbial peptide alpha-amylase inhibitors. PMID- 2581813 TI - Quinine inhibits Ca2+-independent K+ channels whereas tetraethylammonium inhibits Ca2+-activated K+ channels in insulin-secreting cells. AB - The effects of quinine and tetraethylammonium (TEA) on single-channel K+ currents recorded from excised membrane patches of the insulin-secreting cell line RINm5F were investigated. When 100 microM quinine was applied to the external membrane surface K+ current flow through inward rectifier channels was abolished, while a separate voltage-activated high-conductance K+ channel was not significantly affected. On the other hand, 2 mM TEA abolished current flow through voltage activated high-conductance K+ channels without influencing the inward rectifier K+ channel. Quinine is therefore not a specific inhibitor of Ca2+-activated K+ channels, but instead a good blocker of the Ca2+-independent K+ inward rectifier channel whereas TEA specifically inhibits the high-conductance voltage-activated K+ channel which is also Ca2+-activated. PMID- 2581814 TI - Homology between the human vitamin D-binding protein (group specific component), alpha-fetoprotein and serum albumin. AB - 41 Amino acid long N-terminal sequences of the three major human vitamin D binding proteins (group-specific components Gc1F, Gc1S and Gc2) were characterized: they were identical. By computer analyses, the alignment of this N terminal sequence with several sequences of human serum pre-proalbumin and human pre-alpha-fetoprotein was established. PMID- 2581815 TI - Topography of RNA in the ribosome: location of the 5 S RNA residues A39 and U40 on the central protuberance of the 50 S subunit. AB - The internal site of 5 S RNA comprising residues A39 and U40 has been localized on the E. coli 50 S ribosomal subunit by immune electron microscopy. It has been found to be located on the interface side of the central protuberance at the position distinctly apart but very close to the position of the 5 S RNA 3'-end providing evidence for a quite compact folded conformation of the 5 S RNA in situ. PMID- 2581816 TI - Monoclonal antibodies to cytochrome P-450 immunopurify a 45-kDa protein from a human lymphoblastoid cell line. AB - Monoclonal antibodies (MAbs) to rat liver cytochromes P-450 have previously been used for successful immunopurification of cytochromes P-450 from animal tissues. We now report application of this MAb-based immunopurification technique to the human lymphoblastoid AHH-1 cell line. Immunopurification carried out with 3 different MAbs each yielded a 45-kDa polypeptide. The purified protein contains an MAb-specific epitope present on cytochromes P-450, and may therefore be a human cytochrome P-450. PMID- 2581817 TI - Intersubunit RNA-protein contacts in pre- and post-translocated E. coli ribosome. AB - Ribosomal proteins participating in intersubunit RNA-protein contacts (directly interacting with RNA of the opposite subunit) were determined by means of ultraviolet-induced cross-links in pre- and post-translocated ribosomal complexes, as well as in the free 70 S ribosome (tight couple) of E. coli. In these 3 complexes at least L1 and L9 proteins interact with 16 S RNA, while S6, S9/11 and S15 react with 23 S RNA. All these proteins ('hinge-joint' proteins) are clustered on the small protuberance of the 50 S subunit and on the platform of the 30 S subunit. Reduction in the number of other (variable) intersubunit RNA protein contacts in the course of transition from the tight couple to the pre- and, finally, to the post-translocated state, demonstrates gradual loosening of intersubunit interactions in 70 S ribosome. Such a loosening ('opening') of the 70 S ribosome is determined by conformational changes in ribosomal subunits and/or in their relative arrangement, conjugated with alteration of the functional state of the ribosomal complex. PMID- 2581818 TI - Role of separate K+ and Cl- channels and of Na+/Cl- cotransport in volume regulation in Ehrlich cells. AB - Cells resuspended in hypotonic medium initially swell as nearly perfect osmometers, but later recover their volume with an associated KCl loss. This regulatory volume decrease (RVD) is unaffected when nitrate is substituted for Cl or if bumetanide or 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) is added. It is inhibited by quinine, Ba2+, low pH, anticalmodulin drugs, and depletion of intracellular Ca2+. It is accelerated by the Ca2+ ionophore A23187, or by a sudden increase in external Ca2+ and at high pH. A net KCl loss is also seen after addition of ionophore A23187 in isotonic medium. Similarities are demonstrated between the KCl loss seen after addition of A23187 and the KCl loss seen during RVD. It is proposed that separate conductive K+ and Cl- channels are activated during RVD by release of Ca2+ from internal stores, and that the effect is mediated by calmodulin. After restoration of tonicity the cells shrink initially, but recover their volume with an associated KCl uptake. This regulatory volume increase (RVI) is inhibited when NO3- is substituted for Cl-, and is also inhibited by furosemide or bumetanide, but it is unaffected by DIDS. The unidirectional Cl-flux ratio is compatible with either a coupled uptake of Na+ and Cl-, or an uptake via a K+/Na+/2Cl- cotransport system. No K+ uptake was found, however, in ouabain-poisoned cells where a bumetanide-sensitive uptake of Na+ and Cl- in nearly equimolar amounts was demonstrated. Therefore, it is proposed that the primary process during RVI is an activation of an otherwise quiescent Na+/Cl- cotransport system with subsequent replacement of Na+ by K+ via the Na+/K+ pump. There is a marked increase in the rate of pump activity in the absence of a detectable increase in intracellular Na+ concentration. PMID- 2581819 TI - Cell volume regulation in frog urinary bladder. AB - We have studied the problem of cell volume homeostasis in toad and frog urinary bladder by using electrophysiological measurements and an optical measure of cell volume. After osmotically induced swelling, urinary bladder cells spontaneously regulate their volume through a net loss of potassium, chloride, and water. During inhibition of sodium transport by amiloride the cells swell to the same extent as controls, but the volume-regulatory process is blocked. Electrophysiological results under isosmotic conditions indicate that basolateral membrane resistance increases simultaneously with the amiloride-induced rise in apical membrane resistance during transport inhibition. These independent observations indicate that inhibition of apical membrane sodium entry results in a secondary decrease in basolateral membrane potassium permeability. When cells are exposed to calcium-free, hyposmotic Ringer's solution, cell volume regulation is blocked; subsequent addition of the calcium ionophore A23187 is ineffective in restoring the regulatory process. The ionophore does induce volume regulation, however, in amiloride-inhibited, osmotically swollen cells in the presence of external calcium. Calcium thus seems to control basolateral membrane potassium permeability and may be the intracellular mediator of apical and basolateral membrane interactions. PMID- 2581820 TI - Mechanisms of depletion of substance P by capsaicin. AB - Capsaicin is a neurotoxin that can deplete sensory nerves of their content of substance P and interfere with certain sensory functions, such as responses of animals to noxious heat stimuli. In adult guinea pigs, a species that is susceptible to the effects of capsaicin on both substance P content and sensory function, capsaicin induces selective depletion of substance P from dorsal root ganglia and the dorsal spinal cord, sites of the cell bodies and central terminals of primary afferent neurons, respectively. As the onset of thermal analgesia in guinea pigs precedes depletion of substance P, direct neural actions of capsaicin probably account for its effects on sensory function. Capsaicin interferes with the retrograde transport of nerve growth factor (NGF) to the cell bodies of sensory nerves. Decreased availability of NGF at the site of neural protein synthesis leads to decreased synthesis of substance P. After failure of synthesis of substance P, the content of the peptide in sensory nerves gradually decreases until depletion occurs. PMID- 2581821 TI - [Effects of nonsubstituted and polyglucin-substituted 35% blood loss on the electrocardiogram of dogs]. PMID- 2581822 TI - [Amylase fixation by vascular endothelium]. PMID- 2581824 TI - The concentration of 5-phosphoribosyl 1-pyrophosphate in monolayer tumor cells and the effect of various pyrimidine antimetabolites. AB - 5-Phosphoribosyl 1-pyrophosphate (PRPP) was determined in several murine and human cancer cell lines grown in monolayer, and harvested by trypsinization. For all cell lines a large variation in the PRPP concentration (5-1300 pmol/ 10(6) cells was found. A 1-hr incubation in Dullbecco's medium reduced the variation in PRPP concentration. After this incubation the highest concentration was found in the murine B16 melanoma cell line (about 200 pmol/10(6) cells). The human melanoma cell lines IGR3 and M5 and the human colon carcinoma cell line WiDr contained about 100 pmol/10(6) cells. After this preincubation of 1-hr these cell suspensions were used to study the effect of several antimetabolites on PRPP concentration. A 2-hr incubation with 1mM N-(phosphonacetyl)-L-aspartate (PALA) increased the PRPP concentration only in M5 cells, whereas methotrexate caused an increase in all cell lines. When 5-fluorouracil (5FU) was added, no significant decrease was found in any cell line. Addition of 5FU after a 2-hr preincubation with PALA resulted in a lower concentration in B16, M5 and WiDr cells. The prodrug, 5-fluoro-5' deoxyuridine altered the PRPP concentration only in in WiDr cells when it was added after PALA. The activity of the 5FU metabolizing enzyme orotate phosphoribosyl transferase was comparable in B16, M5 and WiDr cells, but much lower in IGR3 cells. PMID- 2581823 TI - [Possible participation of slow Na+--Ca++ channels in realizing cholinergic effects on the cardiac pacemaker]. AB - The effect of the Ca++-permeability inhibitors (Mn ions, Verapamil, D-600) on the bioelectrical activity and cholinergic responses of isolated sinus node involved reduction of the pacemaker rhythm within 30-40 min and a complete inhibition of the bioelectrical discharge as well as a diminished amplitude of the AP and a reduced slope of the slow diastolic and the fast depolarization. The findings seem to be due to an inhibiting of the slow Na+-Ca++ influx by Ca++-antagonists. The prolonged APs and the reduced rate of terminal repolarization might be due to effect of the inhibition on potassium permeability. After electrical stimulation of the efferent nerve or acetylcholine application, the cholinergic reactions were markedly reduced with Mn++ D-600 and Verapamil. The participation of slow Na+-Ca++ channels in cholinergic reactions of pacemaker cells is discussed. PMID- 2581825 TI - Human chorionic gonadotropin in the ectopic gestation. AB - The ectopic pregnancy is a relatively common condition in the south African black patients. The beta-specific subunit radioimmunoassay for human chorionic gonadotrophin (HCG) was utilized in procuring information in our series of 30 patients. Levels of the hormone were significantly lower when compared to normal gestation of similar duration, never exceeding 2000 mIU/ml. The clearance rate of HCG following normal vaginal delivery was about 24 h and less variable than that of ectopic gestation. The half-life clearance rate of HCG in the ectopics could be divided into three phases, suggestive of HCG compartmentalization. The possible buffering effect of this hormone in the maintenance of the receptor saturated pregnancy is discussed. The possibility that the HCG produced by the normal pregnancy is dissimilar to that of ectopic is speculated upon. PMID- 2581826 TI - Studies with monoclonal antibodies prepared against X-31 influenza virus haemagglutinin. PMID- 2581827 TI - Function and distribution of peptides in the nervous system. PMID- 2581828 TI - Reprogramming of metabolic development by restriction of fetal growth. PMID- 2581829 TI - Hybrids from equine LH: alpha enhances, beta diminishes activity. AB - LH hybrids were prepared by combining eLH alpha and eLH beta with the corresponding subunits of oLH, pLH and hCG. Recombinants were isolated by gel filtration and assessed by SDS-polyacrylamide gel electrophoresis under both dissociating and non-dissociating conditions. All combinations of subunits produced hybrid LH molecules. Hybrids prepared by combining eLH beta with oLH alpha, pLH alpha or hCG alpha were very inactive in rat radioligand and Leydig cell in vitro bioassays. Hybrids prepared with eLH alpha were very active in both assays. The greatest potentiating activity was observed when eLH alpha was combined with pLH beta. The resulting hybrid was 49 times as active as pLH in stimulating steroidogenesis by Leydig cells. PMID- 2581830 TI - The retention and ultrastructural appearances of various extracellular matrix molecules incorporated into three-dimensional hydrated collagen lattices. AB - Artificial extracellular matrices composed of collagen, glycosaminoglycans (GAG), proteoglycans (PG), plasma fibronectin (FN), and a hyaluronate-binding protein (HABP) have been prepared that morphologically resemble embryonic extracellular matrices in vivo at the light and electron microscope level. The effect of each of the above matrix molecules on the structure and "self-assembly" of these artificial matrices was delineated. (1) Matrix components assembled in vitro morphologically resemble their counterparts in vivo, for the most part. Scanning and transmission electron microscopy indicate that under our assembly and fixation conditions, collagen forms striated fibrils that are 125 nm in diameter, FN forms 30- to 60-nm granules, chondroitin sulfate proteoglycan (CSPG) forms 27- to 37-nm granules, chondroitin sulfate (CS) assembles into 100- to 250-nm spheres, and hyaluronate (HA) appears either as granular mats when fixed with cetylpyridinium chloride (CPC) or as 1.5- to 3-nm microfibrils when preserved with ruthenium red plus tannic acid. These molecules are known to assume the same configurations in embryonic matrices when the same preservation techniques are used with the exception of FN, which generally forms fibrillar arrays. (2) Addition of various matrix molecules can radically change the appearance of the collage gels. HA greatly expands the volume of the gel and increases the space between collagen fibrils. CSPG at low concentrations (less than 1 mg/ml) and CS at high concentrations (greater than 20 mg/ml) bundle the collagen fibrils into twisted ropes. (3) A variety of assays were used to examine binding between various matrix components and retention of these components in the hydrated collagen lattices. These assays included solid-phase binding assays, negative staining of spread mixtures of matrix components, cryostat sections of unfixed mixtures of matrix components, and retention of radiolabeled matrix molecules in fixed and washed gels. A number of these binding interactions may play a role in the assembly and stabilization of the matrix. (a) HA, CSPG, and FN bind to collagen. CS appears to only weakly bind to collagen, if at all. (b) FN promotes the increased retention of HA, CSPG, and to a very small degrees, CS, in collagen gels. Conversely, the GAG increase the retention of 3H-FN in the gels. Furthermore, FN binds to HA, CS, and CSPG as demonstrated by solid surface binding assays and morphological criteria. The increased retention of GAG and CSPG by the addition of FN may be due to both stabilization of binding to the collagen and trapping of matrix complexes within the gel. (c) HA binds to both CS and CSPG.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2581831 TI - Analysis of morphogenesis and keratinization in transfilter recombinants of feather-forming skin. AB - The relationships between feather morphogenesis, histogenesis, and biochemical differentiation were examined by recombining backskin epidermis and dermis, from chick embryos (Hamburger-Hamilton stages 27-31), with an intervening Nucleopore filter (pore size of 0.4 micron). The filter inhibited normal feather morphogenesis and histogenesis of barb ridges, yet feather-like filaments, which were free of dermal cells, formed from the epidermal cells. Using indirect immunofluorescence, with antiserum against alpha- and beta-keratins, the biochemical differentiation of the feather-like filaments was compared to normal feathers. In the feather-like filaments resulting from tissues of stages 27-29, cells containing beta keratins were occasionally seen at the periphery of the filaments, yet cells containing alpha-keratins were inappropriately located throughout the filaments. In a few feather-like filaments on recombinants resulting from tissues of stages 29.5-31, cells positive for beta-keratins were found in the center of the filament, but again alpha-keratins were also found. Surrounding these cells there were several layers of cells, arranged circumferentially, resembling sheath cells. Some sheath-like cells contained beta keratins. We conclude that although feather epidermal cells, which are separated from their dermis by a Nuclepore filter, can undergo limited morphogenesis and the production of alpha- and beta-keratins, normal feather morphogenesis, histogenesis, and biochemical differentiation require the intimate associations of epidermis and dermis. PMID- 2581832 TI - Polarity of isolated blastomeres from mouse morulae: detection of transcellular ion currents. AB - Eight- to sixteen-cell stage mouse morulae were dissociated with Ca2+-free medium into blastomeres that were labeled with fluoresceinated-succinylated Con A (FS Con A) to mark their apical-basal axes. The vibrating probe was then used to map their extracellular current patterns. The average current density around normal blastomeres approached the resolution of the probe system (0.2 microA/cm2) and was undetectable in the majority of blastomeres. Since the current density at the measuring point outside the cell is known to increase with cell size in other systems, enlarged blastomeres were created by fusing together blastomeres of 4 cell stage embryos in 45% polyethylene glycol. Enlarged blastomeres were then aggregated with normal blastomeres using phytohemagglutinin and cultured to the 8 to 16-cell stage to allow them to become polarized. Such aggregates were then dissociated with Ca2+-free medium to recover polarized, enlarged blastomeres. The enlarged blastomeres were 30-65 microns in diameter and 70% of them generated a detectable current; currents were detected around 83% of those blastomeres larger than 40 micron in diameter. The current pattern in these most reliable cases was predominantly inward apical (11/16 or 69%) and outward basal (15/16 or 94%), with lateral currents about three-fold smaller in amplitude than these apical-basal currents. Lateral currents were undetectable in 53% of the cases. Preliminary data suggest that the inward current is carried in part by Na+ influx and is independent of the Na+,K+-ATPase over the short term. Transcellular ion currents were detectable as long as 4 hr after dissociation, and the apical-basal current pattern was usually stable during that time. In contrast, the fluorescent cap of FS-Con A faded within 7-30 min at 35 degrees C but remained stable in 0.1% azide or 1.5 micrograms/ml cytochalasin D. The electrical polarity therefore persisted after the apical cap of Con A fluorescence was no longer visible. We propose that these transcellular ion currents may be involved in the establishment of blastomere polarity and describe a mechanism of action in an "ion current polarization" hypothesis. PMID- 2581833 TI - Blastoderm-differential and blastoderm-specific genes of Drosophila melanogaster. AB - We have isolated, by molecular cloning, genes expressed differentially at the blastoderm stage of Drosophila melanogaster. Two of the blastoderm-differential genes are reexpressed at later stages, and map to single chromosomal loci 95C and 99E. The sequence at 99E is that encoding the myosin light chain 2. Two other blastoderm-differential sequences are members of multigene families (one of which is B104, or roo) and map to multiple dispersed chromosomal loci. A gastrula differential sequence was found which maps to 71A. Most significantly, we have identified three genes encoding transcripts expressed uniquely at the blastoderm stage; these map to single chromosomal loci: 25D3, 75C, and 99D4-8. At least some of the blastoderm-differential and blastoderm-specific loci appear to be distinct from loci involved in embryonic pattern formation that have been identified in recent genetic "saturation" screens. The procedure of identifying genes specific to the blastoderm stage may thus allow the identification of genes, not previously identified by classical genetic techniques, that are involved in important embryonic processes. PMID- 2581835 TI - Neurotransmitter precursors and metabolites in CSF of human neonates. AB - The amino-acid precursors tryptophan and tyrosine, and the major metabolites 5 hydroxyindoleacetic acid, indoleacetic acid, homovanillic acid and 3-methoxy-4 hydroxyphenethyleneglycol, related to the central neurotransmitters serotonin, dopamine and norepinephrine, were measured in 62 samples of cerebrospinal fluid from human neonates. Means are reported for the samples from 17 medically uncomplicated infants and for the larger group (42 to 45) of infants with medical complications. The latter group was divided according to diagnosis and medication. All groups had significantly higher levels of all compounds in comparison with older children and adults. There were few significant subgroup differences in the group with complications. In both the normal and complicated groups a number of significant correlations were observed between the compounds themselves and with other physiological measures. PMID- 2581834 TI - Improved fluorescent compounds for tracing cell lineage. AB - In this note simple methods for the synthesis of several new fluorescent cell lineage tracers are described. These are fluorescent dextrans with average molecular weights of approximately 11 X 10(3), and with one or more fluorophore molecules covalently coupled to each dextran chain. These fluorescent dextrans are brighter than commercially obtainable products, and can be microinjected using either air-pressure injection or iontophoresis. They are long-lasting and have a uniform distribution in the cytoplasm of embryonic cells, clearly revealing very fine cell extensions such as cilia, axons, and filipodia. A method is also described for covalently attaching free amino groups to fluorescent dextran to make the tracers cofixable with cellular constituents by aldehyde treatment. Fluorescent dextran-amine tracers allow embryonic cell lineages to be studied in fixed, permeabilized, or sectioned embryos. PMID- 2581837 TI - Bibliography of developmental medicine and child neurology: selected books and articles received in 1984. PMID- 2581836 TI - On the positive semiology of acquired aphasia in children. AB - Eleven unselected cases of aphasia in children seen over a three-year period in a neuropaediatric centre are reported. Contrary to current reports in the literature, the children disclosed a semiology similar to that of adults, particularly for frequency and distribution of 'positive signs' such as paraphasias. The reasons for this discrepancy are discussed and an hypothesis of early intrahemispheric specialization is proposed. PMID- 2581838 TI - Carbohydrate antigenic determinant (CA 19-9) and other tumor markers in gastrointestinal malignancies. AB - The serum carbohydrate antigenic determinant (CA 19-9) was assayed in patients with various diseases, and it provides excellent sensitivity for adenocarcinoma of the pancreas (25/27, 93%), while only 4% (2/54) of the patients with benign diseases and none of the 40 healthy subjects showed elevated CA 19-9 concentrations over 37 units/ml as upper normal value. Increased serum carcinoembryonic antigen (CEA) levels over 2.5 ng/ml were observed in patients with pancreatic cancer (18/22, 82%), compared to 22% (12/54) of the patients with benign diseases and 10% (4/40) of the healthy subjects. 12 of the 19, 6 of the 19 and none of the 22 patients with pancreatic cancer exhibited high serum ferritin, beta 2-microglobulin, or alpha-fetoprotein levels, respectively. A significant difference in CA 19-9 was found between patients with pancreatic cancer and gastric cancer, other gastrointestinal (GI) malignancies, other non-GI malignancies, benign digestive diseases or normal populations. PMID- 2581839 TI - The use of fecal alkaline phosphatase as an indicator of intestinal damage. AB - Fecal alkaline phosphatase excretion was evaluated as a marker for intestinal damage in rats. Animals received either intraperitoneal bleomycin or saline. Controls were pair-fed with animals in the bleomycin group throughout the study. Both groups demonstrated similar patterns of fecal alkaline phosphatase excretion. There was, however, marked daily variability of fecal enzymatic activity. Fecal alkaline phosphatase excretion was largely composed of intestinal alkaline phosphatase, which was characterized by enzymatic inhibition with L phenylalanine. Dietary intake as well as daily fecal output and protein excretion were reduced immediately following bleomycin injections and gradually increased to baseline values by 7 days. It appeared that both the direct toxic effects of bleomycin and dietary intake influenced fecal alkaline phosphatase excretion. Routine clinical application of this assay may be limited because of the number of factors which may affect its excretion. PMID- 2581841 TI - Is modulation of HLA display by interferon important in preventing the development of the chronic carrier state of hepatitis B virus in adults? PMID- 2581840 TI - Retinoids alter the direction of differentiation in primary cultures of cutaneous keratinocytes. AB - The effects of vitamin A on the morphological expression of differentiation were studied in cell cultures of cutaneous keratinocytes from the newborn rat. The cells were first cultivated in a medium containing 0.11 mM calcium until a confluent monolayer had been formed. Stratification and terminal differentiation were then triggered by raising the calcium concentration of the medium to 1.96 mM ('normal' culture). The rise in the concentration of calcium was coupled with the addition of retinol (RL) of retinoic acid (RAC) to the medium to produce an excess of vitamin A (high-retinoid culture). Delipidized serum was used to produce a deficiency of vitamin A (low-retinoid culture). The tissue organization and the ultrastructure of the keratinocytes in the stratified culture were the same as those seen in conventional cultures and skin explants. These stratified cultures expressed the morphological features of the epidermis of intact skin. The addition of RL or RAC to the medium enhanced features characteristic of the secretory epithelium, such as the formation of an extensive endoplasmic reticulum, an enlargement of the Golgi zone, and an increase in the number of vacuoles. At the same time, the addition of retinoids diminished features characteristic of the terminal differentiation of the stratified squamous epithelium, such as stratification and keratinization. Deficiency of vitamin A in the medium resulted in a culture with many differentiated layers. The differentiated cells of the low-retinoid cultures contained densely packed tonofilaments and synthesized products that reacted with the monoclonal antibody AE2 that is specific for keratin peptides which are markers of epidermal differentiation. In the cell culture system that is presented here, an excess of retinoids redirected epithelial differentiation from a stratifying and keratinizing epithelium towards a secretory epithelium. This system is a useful tool for elucidating the mechanisms responsible for the effect of vitamin A on the differentiation of epithelial cells. PMID- 2581842 TI - [Laser treatment of intramucosal cancers of the esophagus in inoperable patients]. PMID- 2581843 TI - Antibiotic treatment and relapse in Whipple's disease. Long-term follow-up of 88 patients. AB - Reports of clinical relapse occurring after apparently successful antibiotic treatment of Whipple's disease prompted this review of long-term follow-up of treated patients. Follow-up of at least 1 yr after completion of treatment or 2 yr after diagnosis was obtained on 88 patients with documented Whipple's disease by a review of the medical literature, correspondence with the authors as needed, and questionnaires mailed to academic gastroenterology programs in the United States. Relapse was defined on the basis of morphology (preferably) or clinically, or both. Thirty-one patients relapsed, 6 of whom relapsed twice. Fifty-seven patients did not relapse. The mean time to relapse was 4.2 yr. The mean follow-up period of patients who did not relapse was 8.2 yr. The type and number of relapses were as follows: clinical, 16; central nervous system, 13; arthralgia, 5; gastrointestinal, 1; and cardiac, 2. The clinical, arthralgia, and gastrointestinal relapses were evenly distributed between early relapses (occurring less than 2 yr after diagnosis) and late relapses (occurring greater than 2 yr after diagnosis). All cardiac and central nervous system relapses were late. Twenty-one of 49 patients treated with tetracycline alone relapsed. Two relapses were reported in 15 patients treated with penicillin and streptomycin followed by tetracycline. Three relapses developed in 8 patients treated with penicillin alone. Five of the 16 patients treated with other regimens relapsed. Nine of the 13 patients with central nervous system relapse had been initially treated with tetracycline, 2 were treated with penicillin, and 2 were treated with combinations of antibiotics. Results of treatment of central nervous system relapse were poor in 10 of the 11 patients for whom details were available. Results of treatment of non-central-nervous-system relapse were excellent in 19 of 20 patients. It is concluded that tetracycline alone, or penicillin alone, is not adequate initial therapy for Whipple's disease and that central nervous system relapse is resistant to antibiotic therapy. The authors recommend parenteral penicillin and streptomycin followed by 1 yr of oral trimethoprim sulfamethoxazole therapy or oral trimethoprim-sulfamethoxazole alone for 1 yr as initial therapy for Whipple's disease. Relapse should be defined by demonstration of recurrence of bacilli whenever possible. PMID- 2581846 TI - Palliative dilation of esophageal carcinoma. AB - The authors' experience with palliative dilation of 46 consecutive patients evaluated for squamous cell carcinoma of the esophagus was retrospectively reviewed. Thirty-nine of 46 patients (85%) underwent dilation in order to palliate symptoms, enable endoscopy and biopsy, or prepare for placement of an esophageal prosthesis. Thirty-two of the 46 patients (70%) were treated with radiation therapy and seven (15%) underwent placement of an esophageal prosthesis. Thirty-five of the 39 patients dilated (90%) noted improvement in swallowing, allowing resumption of a soft or regular diet. Complications were noted in three of the 39 patients dilated (8%). The authors conclude that peroral dilation is a safe, effective, and probably underutilized method of palliation in patients with squamous cell esophageal carcinoma. PMID- 2581845 TI - Hyperamylasemia after ERCP with ionic and non-ionic contrast media. PMID- 2581844 TI - Partially purified white bean amylase inhibitor reduces starch digestion in vitro and inactivates intraduodenal amylase in humans. AB - Whether commercial, bean-derived alpha-amylase inhibitor preparations failed to decrease starch digestion in humans because of insufficient antiamylase activity, destruction by gastrointestinal secretions, or decreased activity in the presence of starch is unknown. We used a simple partial purification procedure to markedly concentrate the inhibitor (sixfold to eightfold by total protein content, and 30 40-fold by dry weight). Compared with a commercial preparation and crude bean extract, this partially purified inhibitor inactivated intraduodenal, intraileal, and salivary amylase in vitro faster and more completely (p less than 0.001); its specific activity was not affected by exposure to gastric juice and was only minimally reduced by duodenal juice. Whereas the rate of amylase inhibition by inhibitor was markedly slowed in the presence of nondietary liquid starch, dietary solid starch had only a minimal effect. Consequently, the partially purified inhibitor had no effect on liquid starch digestion, but decreased in vitro digestion of dietary starch in a dose-dependent manner (p less than 0.001). Perfusion of the partially purified inhibitor (2.0, 3.5, or 5.0 mg/ml at 5 ml/min) into the duodenum of humans rapidly inhibited greater than 94%, greater than 99%, or greater than 99.9% of intraluminal amylase activity. We conclude that commercial amylase inhibitors failed to decrease starch digestion in vivo mainly because they have insufficient antiamylase activity. However, a partially purified inhibitor with increased specific activity is stable in human gastrointestinal secretions, slows dietary starch digestion in vitro, rapidly inactivates amylase in the human intestinal lumen, and, at acceptable oral doses, may decrease intraluminal digestion of starch in humans. Such an inhibitor therefore deserves study. PMID- 2581847 TI - Cytoarchitecture of the corpuscles of Stannius in hillstream teleosts, Barilius bendelisis (Ham.) and Garra gotyla (Gray). AB - The teleosts, Barilius bendelisis and Garra gotyla possess corpuscles of Stannius (CS) which are discrete, encapsulated bodies lying in close proximity to the mesonephros. The corpuscular cells are arranged in anastomosing cords which are separated from each other by connective tissue septa and numerous sinusoids. Light microscopically, 2 types of secretory cells comprise the CS in these species. Majority of the corpuscular cells are stainable with AF and PAS in contrast to the nonstainable cells which evince little affinity for the dyes. The fine cytoplasmic granules contained in the stainable cells are polarized on the vascular face in Barilius bendelisis. PMID- 2581848 TI - Adenohypophysial cell types in an Indian freshwater major carp, Catla catla (Hamilton). AB - The different adenocytes in an Indian freshwater major carp, Catla catla (Hamilton) have been studied by employing various modern staining techniques. Altogether, 8 different cell types have been reported in the adenohypophysis of the aforesaid fish. Variations in the staining intensities of the cell types with the different techniques adopted have been detailed. PMID- 2581850 TI - ER "capture" of the skid-row alcoholic. AB - In response to the spiraling anger and frustration voiced by the emergency room (ER) medical staff and the observed negative interactions between the alcohol dependent patient and the ER staff, the author completed a 6-month retrospective review of all patients evaluated by the ER service with a complaint of alcohol abuse, chronic alcoholism, or requesting detoxification. As a result of that study, an ER-based comprehensive approach to the management of this population was proposed. Utilizing an existing Connecticut state statute, a specific approach to manage the skid-row alcoholic arriving repeatedly in the ER was developed. I report on this ER-based model and an approach to "capturing" the skid-row alcoholic. PMID- 2581849 TI - Role of theophylline during the action of SP in vitro on the activity of synaptosomal membrane ATPase (EC 3.6.1.3) from different areas of rat brain. AB - The in vitro action of SP and theophylline on the activities of (Na K) and (Ca Mg) dependent adenosine-5'-triphosphates (ATPase) of crude synaptosomal membranes (SM) of four different areas of rat brain was investigated. The highest activity of (Ca Mg)ATPase was observed in SM from hippocampus. In thalamus with hypothalamus region the highest activity of (Na K)ATPase and the lowest activity of (Ca Mg)ATPase occurred. It was found, that 10 mumol of SP stimulating "alternatively" both (Na K) and (Ca Mg)ATPase activities from different regions may constitute a regulating agent for ionic transport in CNS of rat. Theophylline on concentration of 5 mumol modulates the action of SP on the activities of the investigated enzymes. PMID- 2581851 TI - Cloning specific complete polyadenylylated 3'-terminal cDNA segments. AB - A simple method for extending partial cDNA clones of specific mRNA molecules is described. The method combines plasmid-primed first-strand cDNA synthesis [Okayama and Berg, Mol. Cell. Biol. 2 (1982) 161-170] with second-strand synthesis by primer extension. This approach selects for the synthesis of specific double-stranded cDNAs with complete 3' termini and poly(A) tails. We have used this method to extend preexisting cDNA clones to isolate 3' segments of human beta- and G gamma-globin cDNAs. These recombinants are particularly useful for the construction of templates for in vitro transcription of synthetic polyadenylylated mRNAs and pre-mRNAs. In addition, nucleotide sequence analysis of the cloned gamma-globin cDNA segment defined a previously unreported sequence polymorphism in the 3' untranslated region. PMID- 2581852 TI - Analysis of the antigenic composition of liver specific lipoprotein using murine monoclonal antibodies. AB - Eight monoclonal antibodies have been raised to antigenic determinants within the liver specific lipoprotein complex. Five of these determinants were species and the others non-species specific. No liver specific determinants were identified. Liver specific lipoprotein antigens recognised by the eight monoclonal antibodies were located either on the hepatocyte membrane and/or along the sinusoidal lining wall or in the cytoplasm of liver parenchymal cells. All antibodies but one reacted with the cell membrane of viable human hepatocytes. The molecular weights of four liver specific lipoprotein-determinants were determined by immunoprecipitation. These ranged from 22 000 to 164 000 daltons. PMID- 2581853 TI - Humoral leukocyte adherence inhibition (H-LAI) with basic encephalitogenic protein (BEP) in head and neck cancer. AB - Fourty-five patients with head and neck cancer and 30 healthy subjects were evaluated by a modified humoral leukocyte adherence inhibition assay using basic encephalitogenic protein as antigen. Ninety-three percent of cancer patients gave a positive reaction, whereas every control person remained negative. The results suggest that humoral leukocyte adherence inhibition assay performed with basic encephalitogenic protein may be useful as an early diagnostic tool in head and neck cancer. PMID- 2581854 TI - Posters presented at the Xth International Symposium on Structure and Function of Erythroid Cells (29.8.-1.9.1983, Berlin/GDR). PMID- 2581856 TI - [Human T-lymphocytes--clinical and methodological studies on the detection of Fc IgM- and Fc-IgG-receptor bearing T-lymphocytes (Tm and Tg)]. AB - Several methodical aspects for determination of T lymphocytes with Fc receptors for IgM (TM) and IgG (TG) were studied including separation technique of T cells with E-rosetting, culture conditions of T cells for determination of TM and the rosetting of TM and TG with EA complexes. The bests results were obtained by stabilization of E-rosettes with human serum albumin, after separation of E rosette forming cells lysis of sheep erythrocytes with save hypotonic shock, culturing of T cells in medium containing 20% AB Serum. Furthermore it was shown the possibility using EA complexes produced with not purifieded IgG or IgM anti ox-red-blood cells antisera without lost of specifity for TM and TG. The percentage of TM and TG in peripheral blood of thirty healthy persons as well as monitoring TM and TG in three cases was investigated. PMID- 2581855 TI - Value of prednimustine in treating non Hodgkin's lymphomas of favourable histological type. AB - 24 patients with non-Hodgkin's lymphomas of low-grade malignancy (stage III and IV) were treated either with a single drug (prednimustine) or with combination chemotherapy (cyclophosphamide, vincristine and prednisone). Response to therapy was similar in both groups. Prednimustine induced complete remission in 6 from 13 patients, while in that group treated with combination chemotherapy a complete remission was recorded in 4 from 11 patients. Both regimens were well tolerated. Therapy with prednimustin has an advantage in oral administration enabling it to be used in out-patient practice. PMID- 2581857 TI - [In vitro study of bone marrow from leukemia patients and patients without hematologic disease]. AB - The bone-marrow of 26 patients not affected with hematological diseases and 10 patients with untreated leukemia was investigated according to Dexter in long term cultures. Survival time and cell content of those long-term cultures started with normal bone marrow were not influenced significantly, if reinoculation was made with autologeneic or allogeneic bone marrow. Even without repeated inoculation, leukemic cells grew for a longer time in long-term cultures than normal bone marrow cells. As far as the outcome of the disease is concerned, no conclusion can be drawn from the duration of cultivating leukemic cells growth. PMID- 2581859 TI - Ultrastructural morphometric cell evaluation in chronic lymphocytic leukaemias. AB - The present study was undertaken to check whether there is a correlation between the clinical stage and the ultrastructural morphometric picture of leukaemic cells. The investigations concerned 12 cases of chronic lymphocytic leukaemia. Qualitative morphological differences could not be detected between cells originating from various clinical groups. Morphometric ultrastructural analysis, however, revealed differences in the volume fraction of cytoplasmic cell components, not only between clinical groups, but also within them. None of the clinical groups were homogeneous, but the cases classified to groups 0, I and II were uniform as regards the volume fractions of the nucleus and some cytoplasmic components. Ultrastructural morphometric studies seem to suggest that counterparts to the clinical state may be found in the morphology of leukaemic cells. PMID- 2581858 TI - Activity of cyclic nucleotide phosphodiesterases in granulocytes of chronic myelogenous leukemia (CML). A preliminary report. AB - Cyclic 3':5'-adenosinmonophosphate phosphodiesterase (cAMP-PDE), high KM value type isoenzyme, and cyclic 3':5'-guanosino-monophosphate phosphodiesterase (cGMP PDE), high KM value type isoenzyme, were determined in granulocytes of patients with chronic myelogenous leukemia (CML) in the chronic phase of the disease. Granulocyte cAMP-PDE activity was similar in the general group of CML patients to that in normal granulocytes; the cGMP-PDE, however, was somewhat higher. By dividing the CML general group into the "low leukocyte count" subgroup including granulocytes of patients with WBC number ranging from 10,300 to 40,000 per microliter (mean 22,000 per microliter), and the "high leukocyte count" subgroup including patients with leukocyte count above 40,000 per microliter (mean 67,000) remarkable differences in the activities of cyclic nucleotide phosphodiesterases between these subgroups could be found: cAMP-PDE activity for the high leukocyte count subgroups was significantly higher than for that in normals, and in CML-low leukocyte count subgroup. On the other hand, cGMP-PDE activity in granulocytes of the high leukocyte count subgroup was found to be remarkably lower than that in normals, in the low leukocyte count subgroup and general CML group. In CML patients the ratio of cAMP-PDE activity to cGMP-PDE activity was always considerably higher than that in controls. The obtained results suggest CML granulocytes to differ from normal ones in respect to their control of intracellular cyclic nucleotide levels. This difference is related to the accumulation of CML granulocytes. PMID- 2581860 TI - [Visual classification of erythrocytes in blood smears from normal subjects and patients]. AB - Erythrocytes on specially prepared and coloured blood smears can be classified not only by idcture analysis but also by phase contrast microscopy. Parameters of change for the peripheral zone area and pallor area (phase contrast value PW and index of erythrocyte changes Ev-I) serve as classificators of visual technique. 449 blood smears of the same number of male and female grown-up persons, whose diagnosis was unknown at the time of evaluation, were used for evaluation. In 145 cases these were healthy test persons in clinical and laboratory respect (group I). 163 test persons were ill, but without any malignous neoplasias (group II), and in 141 patients an ensured malignous neoplasia could be found (group III). From those 308 test persons or patients respectively in group I + II 11 blood smears were falsely classified as positive (= 3.6%). In 5 from 141 cases in group III blood smears were falsely evaluated as negative (= 3.6%). The findings were statistically ensured by the t-test. Clinical parameters of evaluation gained with visual techniques of classification are in accordance with those gained with automatic picture analysis. The reasons for the good separating ability of PW and Ev-I are discussed. Visual techniques of classification are suitable for institutions of all grades of equipment. PMID- 2581861 TI - Behaviour of antithrombin III abnormalities in the crossed immunoelectrophoresis system. AB - Antithrombin III (AT III) abnormalities can be characterized by means of crossed immunoelectrophoresis. In the past, it was thought that the abnormalities could be demonstrated only if heparin is present in the system. Now some conditions (AT III Trento, for example) are known to show an abnormal pattern only in the absence of heparin. This indicates that some of the changes are heparin independent. Furthermore, it could be demonstrated that in some cases the abnormality is present only in serum (AT III Vicenza, for example). Therefore, the test should be carried out as a screening procedure both in plasma and serum and in the presence or absence of heparin in every case of suspected AT III abnormality. PMID- 2581863 TI - Serum anti-platelet activity in acute leukemias (AL) and chronic thrombocytopenic purpura (ITP). AB - Serum anti-platelet activity in 44 patients with acute leukemia (AL), 19 patients with idiopathic thrombocytopenic purpura (ITP) and 30 healthy controls was studied by using the platelet factor 3 availability test (PF-3) and the inhibition test of clot retraction. Shortening of the clotting time in PF-3 test performed with isologous platelets was found in 30 of 44 cases as a result of accelerating the intrinsic coagulation pathway. During AL remission in 6 examined cases an effect of this serum activity on autologous platelets was demonstrated. Serum anti-platelet activity was inhibited by rabbit anti-IgG. The obtained results suggest that the activity present in the globulin fraction of AL patients serum may contribute to thrombocytopenia in this disease. The influence of various concentrations and combinations of cytostatics on PF-3 and the inhibition of clot retraction tests were examined in vitro. Out of vincristine, methotrexate, cytosine arabinoside and cerubidine only the combination of cytosine arabinoside and vincristine caused the clotting time in the PF-3 test to be shortened. As a single drug only methotrexate caused an inhibition of clot retraction. PMID- 2581862 TI - Platelet factor 4 release induced by intravenous administration of heparin. AB - When heparin is injected intravenously, it can induce an immediate release of platelet factor 4 PF4), probably from the non-platelet pool of endothelial cells. We evaluated this release in a group of normal subjects and patients with cardiovascular disorders or thrombocytosis after an intravenous injection of a bolus of 5,000 I.U. of a commercial mucous heparin. The mean level in normals was 102 +/- 32 (range 50-160) ng/ml and no correlation was found before and after heparin injection between PF4 and heparin level, body weight or platelet count. Only three cardiovascular patients had an elevated level of PF4 released by heparin (HR-PF4) that could be the expression of an increased platelet turnover, whereas all the patients with thrombocytosis had an extremely elevated level of HR-PF4. These patients have much more PF4 available for the binding sites of endothelial cells since only a small percentage of potential binding sites are normally occupied "in vivo". Although no correlation could be found between platelet count and HR-PF4 in subjects with a normal platelet count or in patients with thrombocytosis there was a positive correlation, however, when all the cases were considered together. The other proteins with heparin affinity, B thromboglobulin, antithrombin III and fibronectin were not influenced by a bolus of heparin and did not correlate in normals as well in patients with HR-PF4. PMID- 2581864 TI - A case of congenital factor XIII deficiency. AB - The case of a 53 years old woman was described in whom a congenital factor XIII deficiency was suspected because of deforming scars and hemorrhagic diathesis. A thromboelastographic declination of elasticity as well as decreased factor XIII level up to 5% of normal range were only found in all hemostatic examinations. In 2 children factor XIII decreased to half of its normal level, whereas in the youngest daughter that level was 25%. Sporadically the girl had mild diathesis. No changes in thromboelastograms were observed in members of the patient's family. The platelet function was unchanged in all examined cases. PMID- 2581865 TI - The effect of HR (O-Beta-Hydroxyethylo-Rutoside, Venoruton) on the deformability of erythrocytes in patients with arteriosclerosis obliterans of lower limbs. AB - Deformability of red cells and plasma levels of cAMP and cGMP were studied in patients with arteriosclerosis obliterans of lower limbs. Deformability of red cells and plasma levels of cAMP were found to be decreased in these patients. Venous injection of HR (Venoruton) in one dose (1,000 mg) to patients, led to an increase of red cell deformability and normalisation of cAMP plasma level. The plasma level of cGMP was not changed. The beneficial effect of HR in arteriosclerosis obliterans depends, first of all, on improving the deformability of red cells. The decreased deformability observed in arteriosclerosis seems to be a result of disturbances in the rate of spectrin phosphorylation of the erythrocyte membrane. By normalising the plasma level of cAMP HR had a considerable influence on the appropriate state of elasticity of the red cell membrane. PMID- 2581866 TI - Cytochemical indices of leukocytes in patients with diabetes mellitus. AB - Cytochemical indices of leukocytes were determined in 16 patients with diabetes mellitus in the period of unbalancing and balancing. The following tests were made: content of glycogen and lipids, acid phosphatase (AP), alkaline phosphatase (AIP), myeloperoxidase (MPO) and nonspecific alpha-naphtol acetate esterase (NANAE) activity. In unbalanced diabetics an evident decrease in the activity of AP and MPO could be noted as well as a decrease of glycogen content and an increase of lipid content. An insignificant decrease could be observed in the activity of ALP and NANAE in granulocytes. A slight increase in the activity of NANAE in monocytes would be found. Balancing this disease induced the increase of all parameters in granulocytes except MPO activity. It is interesting to note that balancing diabetes mellitus deepened the observed changes in the decrease or increase of tested parameters. The presented findings clearly indicate the role of metabolic disorders in diabetes mellitus on the activity of some neutrophilic enzymes and the glycogen and the content of lipids in neutrophils. PMID- 2581867 TI - Serum lipoproteins inhibitors of granulocyte-macrophage (GM) colony formation. AB - Normal and chloroform-extracted human sera, fractionated by Sephadex column chromatography, were tested for inhibitory activity on granulocyte-macrophage (GM) colony formation. This activity was found to be connected with lipoproteins with a molecular weight of about 200,000. Serum native fractions of lipoproteins were isolated and mainly high density lipoproteins (HDL) and very low density lipoproteins (VLDL) were shown to have an unspecific inhibitory activity directed on colony stimulating factor (CSF) action. PMID- 2581868 TI - [Bisalbuminemia. Critical review and report of a case of an acquired form in a myeloma patient]. AB - Hitherto, bisalbuminemia (double albuminemia) was regarded as a rare finding in serum electrophoresis. In its first part, therefore, the present paper briefly refers to history, systematic, appearance, geography, genetics and laboratory problems of anomaly. By means of own observations made in an acquired form of bisalbuminemia in a patient with a myeloma, problems and practical significance of this serum protein anomaly are then discussed in a second part. This serum protein anomaly is likely to occur more frequently than hitherto assumed and after clarification it may contribute to increase our knowledge about indication and technique of the antibiotic therapy. PMID- 2581869 TI - [Alkaline phosphatase in human lymphocytes. I. Cytochemical detection of alkaline phosphatase in normal human peripheral blood lymphocytes]. AB - The present paper deals with a sensitive cytochemical method of identifying alkaline phosphatase (AP) in rosette-forming lymphocytes gained from the peripheral blood of healthy human beings. The percentage of AP-positive lymphocytes amounts to 5%, with all cells comprising B- and O-lymphocyte population and with T-lymphocytes being negative. In a group of healthy test persons, recently, however, having undergone various inflammatory processes or virus diseases, the number of AP-positive lymphocytes is significantly higher, from 41-73% in B- and O-lymphocytes and from 6-38% in T-lymphocytes. This observation indicates that AP in lymphocytes may have a clinical significance in reactive lymphoproliferative processes, which must be elucidated by further investigations. PMID- 2581870 TI - [Alkaline phosphatase in human lymphocytes. II. A method for ultracytochemical detection of alkaline phosphatase in lymphocytes]. AB - For the ultracytochemical identification of alkaline phosphatase in lymphocytes gained from the peripheral blood of healthy individuals a sensitive method is described which allows the low enzyme activity of these cells to be determined. This was possible because the authors succeeded in stabilizing lead ions in the alkaline medium by forming a complex directly between tris-(hydroxymethyl) aminomethan and lead (II) citrate. AP localized ultrachemically in lymphocytes in particular formations similar to phosphasomes of neutrophilic granulocytes. In those lymphocytes stimulated by lipopolysaccharides a high enzyme activity could be observed and, in addition to phosphasomes, the product of response can also be found in canal-like structures of the endoplasmatic reticulum. These findings contribute to clarify the ultrastructural localization of alkaline phosphatase in lymphocytes and may be regarded as an aid in discovering the importance of the enzyme in the biology of lymphocytes or in its activation, respectively. PMID- 2581871 TI - [Interesting relations in the HLA system]. AB - There exists no absolute binding between the antigens HLA-Cw 2, Cw 3 and Cw 4, on the one hand, and HLA-B 27, HLA-B 15 and HLA-Bw 35, on the other hand. Even if 91% of human beings with HLA Cw 4 will simultaneously have the antigen HLA-Bw 35, another antigen as HLA-B 27 or HLA-B 15 can be identified in approximately 55% of individuals with HLA-Cw 2 and Cw 3. In this connection, the joint presence of some pairs of cross-reacting HLA antigens (A 2 and A 28, B 5 and Bw 35, B 7 and B 27, B 8 and B 14, B 12 and Bw 2) could be proved and their frequency be determined. 2 cases of a simultaneous presence of two subtypes of HLA-A 10 antigen, A 25 and A 26, could be found in family examinations. Moreover, two atypical bindings of anti-HLA-Bw 4 and anti-HLA-Bw 6 cytotoxins with HLA antigens could be identified: 7,49% of HLA-Bw 35 positive lymphocytes no positive response with anti-HLA-B 4 and 1,69% of HLA-B 12 with anti-HLA Bw 6. The importance of the findings for determining HLA in practice is discussed. PMID- 2581873 TI - [Plasma fibrinogen in female patients with genital cancer and its early stage]. AB - Changes of plasma fibrinogen derivates in 54 female patients suffering from carcinomas of the genital system (36 with cervix carcinoma, 9 with ovarian carcinomas, 7 with carcinomas of the corpus uteri, 1 woman with a vulva and 1 patient with vaginal carcinoma) and 6 females with cervical intraepithelial neoplasia were investigated. It was shown, that the fibrinogen content and the concentration of soluble fibrin monomer complexes in blood plasma depend on the extension of the clinically diagnosed tumor. Furthermore, differently degraded fibrinogens were demonstrated to exist in the blood circulation. The extent of fibrinogenolysis did not correlate with the clinically diagnosed tumor stage. PMID- 2581872 TI - Activity of some lysosomal enzymes in peripheral blood lymphocytes of patients with lung cancer. A cytochemical study. AB - In 33 patients with lung cancer (6 women and 27 men, aged at average 61.2 years) the activity and intracellular localization of acid phosphatase, beta glucuronidase and N-acetyl-beta-glucosaminidase in peripheral blood lymphocytes were determined by means of semiquantitative cytochemical methods. In comparison to the control group of healthy subjects, the patients with lung cancer showed increased counts of acid phosphatase-positive lymphocytes with granular-diffuse cytochemical reaction, increased counts of beta-glucuronidase-positive lymphocytes with solely granular type of reaction and increased numbers of N acetyl-beta-glucosaminidase-positive cells showing the granular, granular-diffuse and diffuse type of reaction. The total count of beta-glucuronidase-positive and N-acetyl-beta-glucosaminidase-positive lymphocytes was significantly elevated in these patients. The authors discuss the significance of their observations for evaluating lymphocyte response in patients with lung cancer. PMID- 2581874 TI - [Proteolytic changes in plasma fibrinogen from ovarian venous blood in patients with cervix cancer]. AB - From 9 female patients suffering from carcinoma cervicis (8 women with a stage Ib, 1 woman with a stage IIa carcinoma) blood was taken immediately from the ovarian veins and a cubital vein after laparotomy on the occasion of a surgical intervention according to Wertheim-Held. Fibrinogen was isolated from plasmas by affinity chromatography at fibrin monomer Sepharose and characterized by SDS PAGE. With one exception proteolytically changed fibrinogens could be demonstrated in all plasmas. In 7 cases the fibrinogens from ovarian blood were more degraded than fibrinogen derivates in the blood obtained from cubital veins. It is assumed that the proteinase and/or plasminogen activator activities of tumor tissues are of importance for the observed proteolytic effects. PMID- 2581875 TI - [Occurrence and clinical course of drug-induced agranulocytosis]. AB - A report of 27 drug induced agranulocytosis is presented in a period of 13 years. The rate of the disease was 0.12% of the total number of patients. Cases due to cytostatical and radiation treatment were not included. According to bone-marrow cellularity patients were divided into hypo- and hyper-cellular groups. The clinical findings were similar in both groups and the majority of patients recovered. Two patients died, both in the hypocellular group: the first due to mycotic pulmonary infection, the other after massive pulmonary embolism but after complete haematological recovery. Bone-marrow plasmocytosis was slightly expressed in the hypocellular group. The normal leukocyte number appeared after treatment within 3-25 days. Recurrent agranulocytosis was observed in four patients and permanent leukopenia developed in five. The leukocyte-agglutination test was positive in 10 cases only, but the leukocyte migration test was positive in all investigated cases except two. Five patients had a previous history with idiosyncrasy. Treatment was started with antibiotics, corticosteroids and with antimycotic drugs. Sterile island and granulocyte-transfusion was applied in seriously ill patients with septicemic complications only. PMID- 2581877 TI - [For the experienced physician, the construction of an audiovisual podium]. PMID- 2581878 TI - [Histamine release due to ganglion blocking agent and muscle relaxants from rat mast cells]. AB - The mechanisms of histamine release due to d-tubocurarine from rat mast cells have long been known to anesthesiologists, such as degranulatory process, Ca++ dependent process and energy coupled process. However, not much is known about histamine release due to some drugs such as trimethaphan and muscle relaxants other than d-tubocurarine, like alcuronium, pancuronium or succinylcholine, although many clinical reports related to hypersensitivity reactions due to muscle relaxants can be found. In this experiment, the histamine releasing activities of trimethaphan and muscle relaxants were examined using the laboratory model created by Ellis (1970) who reported the selective release of histamine due to d-tubocurarine. Also observed the effects of autonomic neuro effective drugs such as theophylline, isoproterenol or carbamylcholine on histamine release due to d-tubocurarine. From this experiment, it is suggested that trimethaphan releases histamine through nonselective process but muscle relaxants release histamine selectively. It is also found that pancuronium had little effects on rat mast cells and its histamine releasing activity was selective, if any. Histamine release from rat mast cells due to d-tubocurarine was clearly depressed by pretreatment of theophylline or isoproterenol. In the case of carbamylcholine, low doses inhibited histamine release, but higher doses allowed histamine to be liberated from mast cells. From these findings, it is concluded that some drugs like theophylline or isoproterenol may diminish the side effects of d-tubocurarine and perhaps some other muscle relaxants. Also, as theophylline and isoproterenol are concerned, increase of cyclic AMP may play a role in the inhibition of histamine release. The data using carbamylcholine suggested that the cholinergic receptors on the rat mast cells may be involved through the process of histamine release. PMID- 2581880 TI - Evidence for a channel for the electrogenic transport of chloride ion in the rat hepatocyte. AB - Chloride is the major inorganic anion in bile but its mechanism of passage from blood to bile is uncertain. Specific membrane channels account for most net inorganic anion flux in other cell types such as the proximal tubular cell and red blood cell; disulfonic stilbenes inhibit anion movement through these channels. Therefore, we have sought the presence of similar channels in the hepatocyte. Net inorganic anion flux or conductance was initiated in isolated rat hepatocytes by valinomycin in the presence of an outward potassium gradient. Potassium concentration in the extracellular medium increased from 2.75 +/- 0.02 in control cell suspensions to 3.15 +/- 0.04 in valinomycin-treated cell suspensions. Membrane potential difference (Em) (mV), determined as the distribution of [14C]tetraphenyl phosphonium ion was -28 mV in control cells and 42 mV in valinomycin-treated cells (p less than 0.05). Intracellular chloride concentration (36Cl-) (mEq per liter of cell water) decreased significantly from 38.6 in control cells to 32.0 in valinomycin-treated cells. The observed intracellular concentrations (36Cl-) in both control and valinomycin-treated cell suspensions closely approximates values predicted on the basis of the Nernst equation: 41 and 29 (mEq per liter of cell water), respectively, suggesting that the chloride ion is passively distributed on the basis of the membrane potential difference. Furthermore, net rate-limited cell water loss of approximately 15% of control values was associated with the above valinomycin-stimulated changes in ion distribution, as assessed using three methods of cell water volume determination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2581879 TI - Synthesis of heat shock proteins in rat liver after ischemia and hyperthermia. AB - Ischemia of rat liver is followed by recovery or cell death. Since heat shock proteins may be essential to cell survival under stress, we determined levels of heat shock proteins in liver after different periods of blood deprivation and correlated the results with cellular recovery. Cell-free synthesis by poly (A+) mRNA and polysomes revealed 70 and 89 kd proteins which appear similar to proteins produced by the liver of rats with amphetamine-induced hyperthermia. The 70 and 89 kd proteins increased in the liver of rats which recovered from ischemia. PMID- 2581881 TI - Frozen sections of bone biopsies in metabolic and other bone diseases. AB - Frozen sections of bone trephine and needle biopsies can be satisfactorily cut in a standard cryostat and, when stained with haematoxylin and eosin, they enable a rapid diagnosis to be made in a wide range of metabolic bone disorders including Paget's disease, osteoporosis, osteomalacia, hyperparathyroidism and renal osteodystrophy. Neoplastic disease of bone may also be diagnosed using the same technique. A tissue diagnosis can be established within an hour of the biopsy being taken, instead of the 1-3 weeks required for resin section diagnosis, with a consequent potential saving in further costly biochemical and radiological investigations, a possible shortening of the patient's stay in hospital and earlier initiation of correct treatment. The method is quick, reliable and highly cost-effective; it is of particular value in laboratories with insufficient workload to justify the expenditure on specialized microtomes and reagents for resin embedding. PMID- 2581882 TI - Malignant sacrococcygeal teratoma in the adult. AB - This case of a malignant sacrococcygeal teratoma, usually a tumour of early childhood, presented as a bedsore in the lower end of the nuchal cleft of a 69 year-old man and proved to be malignant with a trophoblastic element. The literature of adult sacrococcygeal teratoma is reviewed; we have been able to find only three malignant examples. PMID- 2581876 TI - DNA-protein interactions during replication of genetic elements of bacteria. AB - Specific interactions of DNA with proteins are required for both the replication of deoxyribonucleic acid proper and its regulation. Genetic elements of bacteria, their extrachromosomal elements in particular, represent a suitable model system for studies of these processes at the molecular level. In addition to replication enzymes (DNA polymerases), a series of other protein factors (e.g. topoisomerases, DNA unwinding enzymes, and DNA binding proteins) are involved in the replication of the chromosomal, phage and plasmid DNA. Specific interactions of proteins with DNA are particularly important in the regulation of initiation of DNA synthesis. Association of DNAs with the cell membrane also plays an important role in their replication in bacteria. PMID- 2581883 TI - Optimising human chromosome separation for the production of chromosome-specific DNA libraries by flow sorting. AB - A number of cell lines, some containing chromosomes with distinctive heteromorphisms, have been flow karyotyped using a single laser flow sorter in an attempt to select those suitable for sorting all human chromosomes individually. Using the non-base-specific DNA stain ethidium bromide, chromosomes 3, 4, 5, and 6 form individual peaks in practically all normal subjects, while the right combination of heteromorphisms enables chromosomes 1, 2, 8, 9, 13, 16, 17, 18, 19, 20, 21, 22, and Y to be sorted separately. Two male cell lines, one containing a duplication and one a deletion of the X, produce flow karyotypes suitable for sorting chromosomes 7 and 8. The use of numerical chromosome abnormalities to enrich the sex chromosomes and the autosomes 18 and 21 is also illustrated. The DNA stain Hoechst 33258 binds preferentially to AT base pairs. Flow karyotypes produced with this fluorochrome separate some chromosomes not well separated with ethidium bromide. Chromosomes 5, 6, 8, 13, 14, 15, 17, and 20, and Y can be sorted individually with Hoechst 33258 with the right combination of heteromorphisms. Using these techniques, all human chromosomes apart from 10, 11, and 12 have been found as individual flow karyotype peaks, suitable for sorting with a high degree of purity. PMID- 2581884 TI - Is it possible to analyze DNA and protein sequences by the methods of digital signal processing? PMID- 2581886 TI - [Interferon production and lymphoproliferation in whole blood of schizophrenia patients]. AB - Using a whole blood assay the activity of the interferon system and mitogen induced lymphoproliferation were tested in schizophrenic patients and normal individuals. Leucocytes of the patients produced significantly less interferon than controls after stimulation with the alpha interferon inducers Corynebacterium parvum (CP) or Newcastle disease virus (NDV) and with the gamma interferon inducers PHA and Con A. Differences in the lymphoproliferation test were also measured. Significantly lower responses of the patients were observed when using PHA and Con A as mitogens. PMID- 2581885 TI - [In vitro and in vivo studies with interleukin 2 (IL-2) and various immunostimulants in a patient with AIDS]. AB - We report on a lethal course of an acquired immunodeficiency syndrome (AIDS) in a young female patient. She had spent her vacancies six years before diagnosis in Haiti, where a sexual intercourse with a Haitian man had occurred. Leading clinical symptoms consisted of recurrent Herpes simplex infections of the genital and perianal region as well as unexplained high temperatures. There were some typical laboratory and immunologic features of this disease with leukopenia, hypergammaglobulinemia, cutaneous anergy, a reduction of peripheral T-lymphocytes (OKT 3) and an almost complete loss of OKT 4 (helper cells) positive lymphocytes. The mitogenic response upon stimulation with allogeneic cells (MLC) or with the mitogens PHA, Con A and PWM was significantly reduced. There was no measurable interleukin-2 (IL-2) secretion of peripheral blood lymphocytes. Several immunostimulators (thymopentin, inosiplex, bestatin) were tested in lymphocyte proliferation assays in vitro. The mitogenic response could not be enhanced by neither of these substances. A clinical trial with Delimmun (inosiplex) for 14 days did not show any clinical or immunologic improvement in this patient. The intravenous application of high dose immunoglobulin G was without any observable effect. The proliferation inducing capacity of a highly purified IL-2 preparation on the AIDS cells in vitro led us to a clinical trial with this substance. We applied 100 Bodeker units of IL-2 per kg body weight and day subcutaneously for 16 days. A therapeutical effect, however, could not be observed. Cell marker analyses did not show significant changes in lymphocyte subpopulation composition under IL-2 therapy. There was an increase in the spontaneous cell proliferation 14 days after start of IL-2 therapy. The PHA- and IL-2 response of the AIDS cells, however, was unchanged. It cannot be excluded that an administration of IL 2 in earlier stages of AIDS may have beneficial effects. PMID- 2581887 TI - A monoclonal antibody to the galactan from Helix pomatia snails recognizes beta (1,6)-linked D-galactose residues. AB - Using the hybridoma technique, a series of four monoclonal antibodies to the galactan isolated from albumin glands of wine yard snails (Helix pomatia) could be generated. Characterization of the binding properties of one of these antibodies revealed a specificity for beta-(1,6)-glycosidically linked D galactose residues. This could be demonstrated by reaction of the antibody with beta-(1,6)-D-galactans and by the D-galactose-inhibitable binding to group B streptococci of type II, which possess beta-(1,6)-linked D-galactose as immuno determinant group. PMID- 2581888 TI - Mechanism of follicular trapping: double immunocytochemical evidence for a contribution of locally produced antibodies in follicular trapping of immune complexes. AB - Using two different antigen-enzyme conjugates and a double immunocytochemical staining technique, we demonstrate the localization patterns of two different specific antibodies in the same spleen section. During the early immune responses against simultaneously injected human gamma globulin (HGG), and bovine gamma globulin (BGG) in rabbits, the localization patterns of extracellular anti-HGG antibodies and extracellular anti-BGG antibodies in the follicles overlap only partly. It was shown in earlier studies that extracellular antibodies trapped in the follicles represent antigen-antibody complexes having free binding sites for the antigen. The fact that localization patterns do not overlap extensively, whereas it has been shown in earlier studies that follicular dendritic cells (FDCs) show no specificity with respect to the immune complexes to be captured, leads to the following conclusion. After formation of immune complexes from antibody molecules released by specific antibody-forming cells in the follicles and antigen present in excess between the cells, part of these complexes are trapped by adjacent FDCs. Results are discussed with respect to the possible role of follicular immune complexes in the generation of immunological memory. PMID- 2581889 TI - Five groups of antigenic determinants on DNA identified by monoclonal antibodies from (NZB X NZW)F1 and MRL/Mp-lpr/lpr mice. AB - A library of monoclonal antibodies (MCA) reactive with DNA was derived from mice with lupus-like disease. The combining reactions of the antibodies was determined by ELISA, precipitation assay and indirect immunofluorescence assay on cells. On the basis of their reactions in these assays, the MCA have been classified into five taxonomic groups. MCA in Group I react with conformational determinants on double-stranded DNA (dsDNA); those in Group II with conformational backbone dependent sugar-phosphate determinants on dsDNA and single-stranded DNA (ssDNA); those in Group III with determinants predominantly expressed on ssDNA; those in Group IV with base-dependent determinants on ssDNA, and those in Group V with determinants on both DNA and RNA. It is concluded that antibodies which react with DNA are collectively of limited heterogeneity with regard to their specificity. The study illustrates how, upon traditional interpretation, different assay systems may give discordant results in the assignment of specificity to antibodies reactive with DNA. PMID- 2581890 TI - Altered structure of HLA class I heavy chains associated with mouse beta-2 microglobulin. AB - The serological reactivities of HLA-A3, -B7, and -CW3 heavy chains associated with either mouse, bovine, or human beta-2-microglobulin (beta 2m) and expressed on the surface of transfected mouse fibroblasts were analyzed. All reactivities associated with one cluster (defined by monoclonal antibody W6/32) of antigenic determinants expressed by these HLA class I molecules were lost, or profoundly reduced, after each heavy chain associated with mouse beta 2-m. Expression by the transfected fibroblasts of the HLA-A3, -B7, and -CW3 heavy chains in association with human beta 2m restores these reactivities. Since most of the amino acid differences between mouse and human beta 2m probably correspond to externally oriented hydrophilic residues, these results suggest that critical interactions in the three-dimensional structure of HLA class I molecules occur between the light chain and the first two external domains of the class I heavy chains, to which some of the altered reactivities have been mapped. PMID- 2581892 TI - Reversal of H-2-restricted hyporesponsiveness to human growth hormone by the use of aluminum hydroxide as adjuvant. PMID- 2581893 TI - Analysis of the Qa-4 allodeterminant. PMID- 2581891 TI - Expression of an HLA-Bw6-related specificity by the HLA-Cw3 molecule. AB - Radioimmunoassay of HLA-transformed mouse L cells expressing A3, A24, B7, or Cw3 HLA class I molecules with a set of monomorphic monoclonal antibodies distinguishes between A3-A24 and B7-Cw3 patterns of reactivity. Analyses with Bw6 specific monoclonal antibodies and a human alloantiserum demonstrate the expression by the HLA-Cw3 molecules of a Bw6 public specificity related to but not identical with that expressed by the HLA-B7 molecules. Exon-shuffling experiments and inhibition studies of monoclonal antibody cell-surface fixation indicate that similar parts of B7 and Cw3 molecules account for their serological cross-reactivity. PMID- 2581894 TI - T-cell dependency of the antibody response to free small synthetic peptides of a protein: demonstration with an antigenic site of myoglobin. AB - Recent studies from this laboratory have found that synthetic peptides of proteins, as small as 6 residues, when administered in their free form (i.e. without coupling to any carrier) elicit the formation of antibodies with submolecular binding specificities to preselected protein regions. These peptides could represent either the antigenic sites of the protein or surface regions that are not immunogenic when the intact protein is the antigen. In either case the antibodies bind specifically to the intact protein, exclusively at the region used in immunization. In the present study we immunized BALb/c.ByJ and nude (BALb/c derived) strain mice with either Mb or synthetic antigenic site 5 of Mb. Radioimmune antibody binding studies showed that immunization of BALb/c.ByJ strain mice with either Mb or synthetic peptide resulted in the formation of antibodies that bound specifically to Mb, whereas nude mice did not produce such antibodies. These results indicate that the antibody response to both Mb and synthetic antigenic site is T-cell dependent. PMID- 2581895 TI - Characterization of adenosine-bovine serum albumin immunogen and its antibodies. AB - Antibodies to adenosine were elicited in rabbits using a conjugate of adenosine (periodate oxidized) and bovine serum albumin as immunogen. The conjugate was found to be of a higher molecular size than the original protein, apparently due to the cross-linking of albumin molecules by the dialdehydes generated during the periodate oxidation of adenosine. It produced high titres of antibodies, which were 400-fold more reactive to adenosine-trialcohol than to adenosine, when measured by a nitrocellulose filter assay. In addition, a specific elution procedure for the isolation of hapten-specific antibodies is described. PMID- 2581896 TI - Sodium channel blockers are vasodilator as well as natriuretic and diuretic agents. AB - Amiloride (100-400 micrograms) injected intra-arterially into the dog forelimb perfused at constant flow produced a prompt but transient dose-dependent decrease in perfusion pressure. Intravenous injection lowered systemic arterial pressure, but effects were small and transient except in doses exceeding 10 mg. We tested 11 analogues of amiloride, 3 other diuretics, and a hypotensive imidazopyrazine for vasodilator activity in the dog forelimb and found one analogue, 6-iodo amiloride, with twice the activity of amiloride. Intravenous injection of 3 mg of 6-iodo-amiloride promptly decreased systemic arterial pressure and forelimb perfusion pressure 65 and 47 mm Hg respectively. The decreases with 3 mg of amiloride were only 5 and 23 mm Hg respectively. Intravenous infusion of 17 to 77 mg of 6-iodo-amiloride produced diuresis, natriuresis, and antikaliuresis and, with the higher doses, hypotension. The latter occurred promptly on starting the infusion and was sustained for the duration of the infusion. Wistar rats responded to an intravenous infusion of 0.38 mg/100 g in 11 minutes in the same manner. In the spontaneously hypertensive rat, this same dose produced a large, sustained antihypertensive effect with little change in the urinary parameters. These studies indicate that 6-iodo-amiloride is a vasodilator and a vasodepressor as well as natriuretic and diuretic in the normal dog and rat and that it produces a sustained, large fall in blood pressure, independently of urinary effects, in the spontaneously hypertensive rat. These results suggest that 6-iodo amiloride and other sodium channel blockers might be useful as vasodilatory antihypertensive agents, particularly in those types of hypertension characterized by increased vascular smooth muscle cell permeability to sodium. PMID- 2581897 TI - The antihypertensive function of the kidney. Its elucidation by captopril plus unclipping. AB - Unclipping the one-kidney, one-clip hypertensive rat during a free flow of urine caused the blood pressure to return to normal levels within about 3 hours. We found that administration of captopril plus unclipping caused the blood pressure to return to normal in minutes (17 +/- 4). Ureterocaval anastomosis plus captopril plus unclipping also caused the blood pressure to return to normal in minutes (8.8 +/- 2). Thus, the potentiation of the drop in blood pressure does not seem to be due to a volume effect. Administration of indomethacin and aprotinin did not prevent a rapid decline of the blood pressure after unclipping, but the decline was less rapid than that occurring after captopril and unclipping, which suggests that prostaglandin may have some effect on this mechanism. Saralasin administration did not potentiate the antihypertensive action of captopril plus unclipping. Chemical papillectomy prevented the drop in blood pressure after unclipping. The bolus dose of captopril to the hypertensive rat often caused a transient depressor effect resembling that due to the antihypertensive neutral renomedullary lipid, which suggests secretion of this lipid into the blood. The renomedullary interstitial cells accumulated large lipid granules after captopril administration. These cells also degranulated after unclipping. These findings are consistent with the hypothesis that the renal papilla secretes an antihypertensive hormone after unclipping. At present, antihypertensive neutral renomedullary lipid is the main putative hormone. PMID- 2581898 TI - Immunization against experimental murine salmonellosis with liposome-associated O antigen. AB - Partially delipidated Salmonella typhimurium (O-1,4,5,12) lipopolysaccharide was incorporated into small multilamellar liposomes composed of either naturally occurring or synthetic phospholipids. Vaccination of mice with the liposome lipopolysaccharide complexes induced a cellular response specific for O-1,4,5,12 determinants, as determined by the development of a delayed-type hypersensitivity reaction. The liposome-lipopolysaccharide vaccines were significantly more effective, compared with other nonviable vaccines tested, in protecting mice against a lethal intravenous challenge infection with virulent S. typhimurium. Protection afforded by the liposome-lipopolysaccharide vaccines was comparable to that conferred by a live S. typhimurium vaccine. Results suggest that liposome induced modulation of the host immune response in favor of cell-mediated immunity may be more efficacious in preventing diseases in which cell-mediated immunity is of prime importance. PMID- 2581900 TI - Characterization of two different antibody specificities recognizing distinct antigenic determinants in free lipid A of Escherichia coli. AB - Antisera were raised in rabbits with acid-treated Re mutant bacteria from Salmonella minnesota and Escherichia coli and tested in a passive hemolysis assay with di- and monophosphorylated free lipid A of E. coli (LipA-Ac and LipA-HCl, respectively) coated onto sheep erythrocytes. Depending on the acid used to prepare the immunogen (acetic versus hydrochloric acid), different antibody specificities were obtained. Antiserum prepared against HCl-treated bacteria was found to react with both antigens to the same extent (i) in the passive hemolysis test, (ii) in the passive hemolysis inhibition test, and (iii) in absorption experiments, suggesting that antibodies in this antiserum recognize an antigenic determinant equally present in LipA-Ac and LipA-HCl. Antiserum raised against acetic acid-treated bacteria reacted with the homologous antigen (LipA-Ac) in the passive hemolysis and passive hemolysis inhibition test as well as in absorption experiments. However, the antiserum failed to react with the heterologous antigen (LipA-HCl) in the hemolysis test and during absorption, whereas in inhibition studies interaction of this antiserum with both antigens was observed. The inhibiting capacity of LipA-Ac was lower compared with that of LipA-HCl, indicating that the antigenic determinant of LipA-Ac is partly expressed by LipA HCl in solution, but not when fixed on the surface of sheep erythrocytes. The role of glycosidically linked phosphate in lipid A is discussed with respect to antigenicity. PMID- 2581899 TI - A completely synthetic toxoid vaccine containing Escherichia coli heat-stable toxin and antigenic determinants of the heat-labile toxin B subunit. AB - The immunodeterminant regions of the Escherichia coli heat-labile toxin B subunit were identified by determining the antigenicity, by using enzyme-linked immunosorbent assays, of synthetically produced peptides corresponding to various segments of its 124-amino-acid sequence. The addition of the 18-amino-acid sequence of heat-stable toxin (ST) to some of these peptides enhanced their B subunit antigenicity. Peptide residues containing the 26 amino acids of B subunit sequence 58 to 83 joined to the 18-amino-acid sequence of ST yielded a 44-amino acid peptide whose antigenicity was 50% that of both native B subunit and ST. This peptide was completely nontoxic when tested in Chinese hamster ovary tissue culture, suckling mouse, and rat ligated ileal loop assays. Peroral immunization of rats with the polymeric form of this peptide yielded a dose-dependent response of intestinal immunoglobulin A antitoxin titers to both the ST and B subunit components and provided strong protection against challenge with viable ST- and heat-labile toxin-producing E. coli strains. The immunogenicity of the synthetic peptide in rats was the same as that of ST and about 50% that of native B subunit. The completely synthetic peptide vaccine has the following advantages over previously described toxoid vaccines that consist of synthetic ST chemically cross-linked to native B subunit derived from bacterial cultures: it is produced by a single synthetic process, it is completely nontoxic, and it is immunogenic for both ST and B subunit. PMID- 2581901 TI - Differential action of six human interferons against two human carcinomas growing in nude mice. AB - Six different pure human interferons (IFNs), were tested for anti-tumour effect against two human carcinomas, breast and bowel, growing in nude mice, in a total of 36 experiments. The IFN-alpha mixture, analogue and subtypes showed the greatest activity, particularly against the breast cancer xenograft, whereas IFN beta and IFN-gamma had little effect. However, circulating IFN could be found in the sera of mice treated with all 3 IFN types. In terms of amount of IFN protein, IFN-alpha Con1, an IFN-alpha analogue, was the most effective, a dose of 0.1 micrograms/mouse/day being sufficient to induce breast tumour regression, and IFN gamma the least effective, a dose of 10 micrograms/mouse/day having no effect on the same tumour. A more detailed comparison of 2 IFN-alpha subtypes showed that a daily dose of 1 microgram IFN-alpha A was more effective than the same dose of IFN-alpha D, but as this IFN had approximately 30 times less antiviral activity on human cells than IFN-alpha D, these IFNs were probably at least equally effective in terms of human cell units. IFN-alpha D stimulated mouse spleen natural killer cell activity but it was not clear whether this stimulation was involved in anti-tumour activity. We conclude that this model system is useful for investigating direct anti-tumour activity of a wide range of IFN types and subtypes. PMID- 2581902 TI - Use of novel chemical supplements in the establishment of three human malignant lymphoma cell lines (NU-DHL-1, NU-DUL-1, and NU-AMB-1) with chromosome 14 translocations. AB - Three new cell lines have been established from patients with malignant lymphoma utilizing a human diploid feeder layer, pooled human serum, and the chemical supplements L-cysteine, iron-saturated transferrin, and bathocuproine disulfonate, a copper chelator. After a short period of growth, the 3 cell lines were successfully weaned from the feeder layers but continued to require human serum and the chemical supplements for up to 9 months of culture. The cell lines are currently grown in RPM1-1640 medium and fetal calf serum without further supplementation. The NU-DHL-1 cell line was established from the involved lymph node of a 73-year-old White male with diffuse large-cell lymphoma. The cell line expresses cytoplasmic IgM/lambda heavy and light chains, is Epstein-Barr virus (EBV)-negative, and is positive for several B-cell markers, indicating that it is derived from a mature-B-cell neoplasm. The NU-DUL-1 cell line was established from the cerebrospinal fluid of a 42-year-old White male with undifferentiated lymphoma, non-Burkitt's type, who initially presented with a mediastinal mass and had subsequent involvement of the central nervous system. The cell line is EBV negative, but surprisingly it is positive for early B-cell markers. The NU-AmB-1 cell line was established from the abdominal mass of a 12-year-old Hispanic male with undifferentiated lymphoma, Burkitt's type. The cell line is EBV-positive and expresses early B-cell markers. All 3 cell lines are aneuploid or pseudodiploid and contain chromosome 14q+ abnormalities including a newly described complex translocation t(?;1;8;14) in the NU-AmB-1 cell line. The establishment of these cell lines was made possible by refinements in the cell culture of the human malignant lymphomas. The availability of well-characterized lymphoma cell lines with specific chromosomal translocations will aid molecular and cellular studies designed to identify the biological significance of genomic rearrangements. PMID- 2581903 TI - Methylation pattern of human T-cell leukemia virus in vivo and in vitro: pX and LTR regions are hypomethylated in vivo. AB - The methylation patterns of the gag, pol, env, pX and LTR regions of proviral DNA of human T-cell leukemia/lymphoma virus type I (HTLV) in fresh leukemic cells and established cell lines were examined using HpaII/MspI endonuclease. Peripheral blood lymphocytes (PBL) isolated from patients with adult T-cell leukemia/lymphoma (ATL) did not express viral antigens of HTLV, but PBL that had been cultured for 2 days did express these viral antigens. Most parts of the gag, pol and env regions of the HTLV provirus in PBL isolated from 12 ATL patients and PBL cultured for 2 days were hypermethylated as reported by others. In contrast, in 10 established cell lines that harbored HTLV genomes and expressed viral antigens, HTLV proviruses were hypomethylated. In one cell line, ATL-IK, which harbored an HTLV genome but did not produce viral antigens, the gag, pol and env regions were hypermethylated. However, two HpaII sites, one in the middle of the gag region and the other in the middle of the pol region, were not methylated even in PBL from most ATL patients. Furthermore, the pX and LTR regions were hypomethylated not only in established cell lines but also in PBL of ATL patients. The hypomethylation of the pX and LTR regions detected in fresh leukemic cells of ATL patients may have some etiological significance in cell transformation by controlling the level of transcription of these regions, or modulating the binding of some factors to these regions. PMID- 2581904 TI - Pharmacologic studies of the central action of zopiclone: effects on locomotor activity and brain monoamines in rats. AB - To investigate the effects of zopiclone on the central nervous system, we examined the effects of zopiclone on brain monoamines such as dopamine (DA), noradrenaline (NA) and serotonin (5-HT) and their metabolites such as homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), as well as locomotor activity in comparison with those of nitrazepam and flurazepam. Zopiclone in a dose of 10 mg/kg (p.o.) significantly reduced it (p less than 0.01) in 30 min and the reduced locomotor activity persisted until 180 min. The reducing effect on locomotor activity by zopiclone was similar to that of nitrazepam and more potent than flurazepam. The effects of zopiclone on brain monoamines (MA) were examined. No significant changes in DA, NA and 5-HT were observed, but HVA and 5-HIAA were reduced. A fluorescent-histochemical study conducted simultaneously revealed almost the same results as the biochemical test results. From the facts that zopiclone inhibited locomotor activity in rats, and inhibited brain DA and 5-HT turnover, the mechanism of action of zopiclone in brain MA neurons seems to be similar to that of benzodiazepine derivatives. PMID- 2581905 TI - Immunomodulating activities of ethylene-2,2'-bis(dithio)bis(ethanol) and related compounds. Effects on murine lymphocyte proliferation and functions in vitro. AB - HEDS (2-hydroxyethyl disulfide) and structurally related compounds were found to affect lymphocyte proliferation and functions in vitro. HEDS, and ADA 202-718 (ethylene-2-2'-bis(dithio)bis(ethanol], were shown to stimulate the proliferation of murine spleen cells. The growth of populations of murine T-cells (thymocytes) was not stimulated. HEDS and ADA 202-718 enhanced the allogeneic response in the mixed lymphocyte reaction and stimulated the formation of antibody producing cells in a primary humoral immune response. A similar stimulatory effect was observed in a secondary humoral response towards a T-cell specific antigen, DNP keyhole limpet hemocyanine. Neither ADA 202-718 nor HEDS exhibited gamma interferon inducing ability, when tested on quiescent Balb/c spleen cell cultures in absence of antigen. However, HEDS, and especially ADA 202-718 potentiated the allogen-induced gamma-interferon production and release in the mixed lymphocyte reaction. Both HEDS and ADA 202-718 seemed to induce or stimulate the release of an interleukin-1-like activity as well as interleukin-2 in Balb/c spleen cells. No obvious effect, however, was seen with either compound on maturation or immune phagocytic activity of bone-marrow derived macrophages. PMID- 2581906 TI - Inhibition of lectin-induced lymphocyte activation by 2-cyclohexene-1-one: analysis of DNA synthesis in individual cells by BUdR quenching of Hoechst 33258. AB - A novel technique utilizing the quenching of fluorescence Hoechst 32258 by bromodeoxyuridine (BUdR) was used to investigate the effect of depressed glutathione (GSH) on the activation of human peripheral blood lymphocytes by phytohemagglutinin (PHA) or concanavalin A (con A). This technique allows the quantification of DNA synthesis in individual cells. Lymphocytes were purified by Ficoll-Hypaque density gradient centrifugation and treated with 5 X 10(-5) M to 1 X 10(-6) M 2-cyclohexene-1-one (2-CHX-1), a reagent which specifically depletes intracellular GSH, and/or interferes with GSH-protein interactions, and 25 micrograms/ml BUdR in the presence or absence of PHA or con A. At 72 h lymphocyte smears were stained with Hoechst 33258 and examined using a computer controlled microscope photometer. When DNA synthesis was assayed using BUdR quenching two populations of lymphocytes were noted; a population which incorporated little or no BUdR (unactivated) and a population which incorporated BUdR sufficient to quench 33258 fluorescence by approximately 35%. Cells treated with graded doses of 2-CHX-1 which reduced glutathione levels by 10-90%, showed a progressive loss of cells from the activated population and the appearance of these cells in the inactivated population. Statistical analysis of the frequency histograms demonstrated that there were no cells which incorporated an intermediate amount of BUdR. This data demonstrates that depressed intracellular GSH or inhibition of GSH-protein interactions inhibits an early step in the biochemical sequence of events leading to DNA synthesis but does not inhibit the DNA synthetic process per se. PMID- 2581907 TI - Effects of isoprinosine in animal models of depressed T-cell function. AB - Isoprinosine--a new drug possessing immunostimulating properties--was investigated for its ability to influence cell-mediated immune responsiveness in animal models of deficient T-cell function. In vitro isoprinosine strongly increased T-cell mitogenesis in spleen cells from normal rats, with only modest increases in B-cell mitogenesis and no effects on unstimulated cells. In vivo isoprinosine (50 mg kg-1 day-1 orally) had no effects on spleen cell responsiveness when administered to normal rats for 4 or 14 days. However, when the same dose of isoprinosine was administered to rats immunosuppressed with cyclophosphamide (5 mg kg-1 day-1 orally) a partial restoration of T-cell mitogenesis was observed after 14 days of treatment. In rats with adjuvant arthritis treated with isoprinosine for 14 days, depressed T-cell responsiveness was completely restored to the level of the nonarthritic animals. The involvement of different cell types in the observed effects of isoprinosine was further studied in arthritic rats. Removal of monocytes/macrophages from the cell suspensions prior to culture did not affect the increased T-cell response in isoprinosine-treated rats, suggesting a direct stimulatory effect of isoprinosine on T-cell functions. T-suppressor cell function, impaired in arthritic rats, was not restored by treatment with isoprinosine. These results suggest that isoprinosine may exert selective effects on specific T-cell subsets, a finding that may increase the therapeutic interest of the drug. PMID- 2581908 TI - Environmentally induced systemic sclerosis-like disorders. PMID- 2581909 TI - Lens-induced inflammation. AB - Eight cases of lens-induced inflammation are described, demonstrating the variations in the histopathological appearance. PMID- 2581910 TI - Inhibition of excision repair of DNA in u.v.-irradiated Escherichia coli by phenethyl alcohol. AB - Membrane-specific drugs such as procaine and chlorpromazine have been shown to inhibit excision repair of DNA in u.v.-irradiated E. coli. One possible mechanism is that, if association of DNA with the cell membrane is essential for excision repair, this process may be susceptible to drugs affecting the structure of cell membranes. We examined the effect of phenethyl alcohol, which is a membrane specific drug and known to dissociate the DNA-membrane complex, on excision repair of DNA in u.v.-irradiated E. coli cells. The cells were irradiated with u.v. light and then held at 30 degrees C in buffer (liquid-holding) in the presence or absence of phenethyl alcohol. It was found that phenethyl alcohol inhibits the liquid-holding recovery in both wild-type and recA strains, corresponding to its dissociating action on the DNA-membrane complex. Thus, the association of DNA with cell membrane is an important factor for excision repair in E. coli. Procaine did not show the dissociating effect, suggesting that at least two different mechanisms are responsible for the involvement of cell membrane in excision repair of DNA in E. coli. PMID- 2581911 TI - Abnormal retention of X-irradiated ataxia-telangiectasia fibroblasts in G2 phase of the cell cycle: cellular RNA content, chromatin stability and the effects of 3 aminobenzamide. AB - We have addressed three aspects of the abnormal sensitivity of SV40 transformed ataxia-telangiectasia (A-T) fibroblasts to X-irradiation, namely: (a) the radiogenic perturbations in cell-cycle traverse analysed by flow cytometry; (b) the involvement of 3-aminobenzamide-sensitive processes in cellular recovery in terms of viability and release from G2 + M phase delay; and (c) the functional and structural integrity of cells delayed in G2 + M phase using acridine orange as a probe for cellular RNA content and chromatin structure. We report that A-T cells show a dose-dependent and survival-related abnormal retention in G2 + M phase due to the lack of a recovery process, despite the capacity of such cells to synthesize ribosomal RNA and maintain the structural integrity of chromatin. Evidence is presented that the recovery process is dependent upon poly(ADP ribosyl)ation activity in both normal and A-T cells except that in the latter cell type recovery potential is rapidly saturated in terms of X-ray dose. PMID- 2581912 TI - Effects of pinealectomy on regional brain serotonin metabolism. AB - The influence of pinealectomy on serotonin cerebral metabolism was examined in male rats maintained in a long photoperiod (14 h L:10 h D). Eight weeks after pinealectomy, serum, hepatic and CNS concentrations of tryptophan were not affected. The concentrations of 5-HT was significantly decreased in only three regions, hypothalamus, midbrain and hippocampus. The levels of 5-HIAA decreased significantly only in the hypothalamus and the midbrain. These results suggest that pinealectomy promotes a decreased hypothalamic and midbrain 5-HT utilization. PMID- 2581913 TI - Double-blind study with Serocytol "Muqueuse urinaire" and "S.R.E." in patients with urological disorders. AB - A double-blind study with Serocytol "Muqueuse urinaire" (immune serum against mucosa of the urinary tract) and Serocytol "S.R.E." (immune serum against reticulo-endothelial system) and placebo was designed for treatment of different bladder diseases (interstitial cystitis sui generis, after radiotherapy and in connection with multiple transurethral resections of bladder tumour, cystitis granularis). Twenty-four patients (17 women and 5 men, aged 41-75, with interstitial cystitis, and 2 women, aged 42 and 75, with cystitis granularis) were included in this study. According to the procedure and after breaking the code 13 patients were treated with Serocytol and 11 patients with the placebo. Nine out of 13 patients who were treated with Serocytol showed an improvement of their condition. In 1 patient the condition was unchanged. Three patients treated with the active compound dropped out of the study during the treatment phase. In one instance the patient did not appear for further check-up; in another the therapy was discontinued after 3 weeks, and in one case a general exanthema occurred. Of the 11 patients treated with placebo, there was an improvement in 2 patients, whereas in 9 cases their status was unchanged. Serocytol and placebo were well tolerated by most of the patients. There were no side effects resulting from the almost daily suppository application over a period of 2 months. No changes in the blood counts, electrolytes, liver and renal function could be found in any of these patients. PMID- 2581914 TI - Testicular germ cell tumours. Current problems of histogenesis and classification. AB - Testicular germ cell tumours, owing to their variety in biological behaviour and morphological appearance, claim a place of their own in clinical oncology and tumour research. Much of the histogenesis has remained unexplained, as reflected by the different systems of pathological classification. This report sums up, on basis of the literature, the current pathologic views on the question of testicular tumour genesis. Data obtained from immune histochemical examinations, animal experiments, ultrastructure studies, together with clinical observations, suggest that differentiation of the carcinomatous stem cells are apt to produce forms, transitional between seminomatous and non-seminomatous types of tumour. The possibility to set up a uniform, clinically appropriate nomenclature depends on the progress in histogenetic knowledge. PMID- 2581916 TI - Psychophysics of reading. III. A fiberscope low-vision reading aid. AB - Existing reading aids providing magnification in excess of 6X (24 diopters) are awkward to use, expensive, or not portable. The authors have developed a new type of reading aid, a low-resolution fiberscope, that provides magnification up to 40X (160 diopters), and is easy to use, inexpensive, and portable. The fiberscope consists of an objective-lens assembly, a flexible bundle of optical fibers, and an eyepiece that together transmit an image from the page to the reader's eye. Complete construction details are included. The design is based on the authors' previous findings that reading requires a field of only four characters and a resolution of only 2 cycles/character. After only half an hour of training, a diverse group of low-vision readers read with the fiberscope at rates between 12 and 95 words/minute. Low-vision readers with central field loss had a median reading rate of only 18 words/min, whereas those with intact central fields had a median reading rate of 67 words/min, not far short of the median rate of 73 words/min for normal readers using the fiberscope. This is consistent with the authors' previous findings that low-vision readers with central field loss read much more slowly than those with intact central fields, even when optimal magnification is provided. The authors conclude that the fiberscope may be very useful as an inexpensive portable reading aid for people requiring high magnification. PMID- 2581915 TI - Light and temperature modulated staining of the rod outer segment distal tips with Lucifer yellow. AB - External application of the dye Lucifer yellow to isolated retinas of Xenopus laevis causes a specific staining of the distal tips of the rod outer segment (ROS). Staining occurs most frequently in the distal 4 micron of the ROS and does not diffuse throughout the ROS cytosol. In contrast, damaged ROS fill with the dye and exhibit a diffuse fluorescence. Retinas from constant light-treated animals show a greater frequency of labeling when isolated in the light than when isolated in the dark after 0.5 and 3 hr. Increased frequency of distal tip staining for dark-treated animals can be achieved if animals are returned to the light. Distal tip labeling also occurs in cyclic-light maintained animals but at a much lower frequency. The frequency of distal tip staining can also be altered by temperature and metabolic poisons. Isolated retinas exposed to dye solutions kept at either 3 degrees C or containing the metabolic poisons, iodoacetate or dinitrophenol, exhibited a reduced frequency of staining. This suggests that staining is an active process involving cellular metabolism. The distal location, dimensions, and light dependence of staining suggests that labeled regions are destined for detachment as part of disc shedding. The sensitivity of distal tip staining to metabolic poisons suggests that the photoreceptor plays a role in determining the membrane domains destined for shedding. PMID- 2581918 TI - Monitoring liver regeneration after right hepatectomy. AB - Factor VII coagulant, prothrombine time, fibrinogen, prealbumin and a fetoprotein have been evaluated in a patient operated on for right hepatectomy, in order to identify the best markers in prognosing liver regeneration. Factor VII and prothrombine time progressively increased, starting from the 5th-7th day, entering normal range by the 10th and demonstrated a good correlation with both liver scintiscan and ultrasonography. Prealbumin and fibrinogen did not provide any useful information and a fetoprotein levels progressively decreased, demonstrating the complete removal of the neoplastic tissue. Factor VII and prothrombine time seem therefore to be the most reliable markers, among those investigated in this study, of liver regeneration after partial hepatectomy. PMID- 2581917 TI - Myelin basic protein and S-100 antigen in cerebrospinal fluid of patients with multiple sclerosis in the acute phase. AB - It has previously been demonstrated that both Myelin Basic Protein (MBP) and S 100 are released in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients during acute phases of exacerbation of the disease. In order to investigate the pathobiological significance of the release of these two proteins into the CSF, MBP and S-100 were assayed in 10 MS patients during the five weeks following onset of an acute exacerbation. MBP was detectable in CSF during the first three weeks after exacerbation, while S-100 was detectable during the entire period of observation, at least in some of the patients. MBP reached its highest CSF concentrations during the first two weeks while S-100 did so in the third week, decreasing thereafter. This difference in time of presence of MBP and S-100 in the CSF is probably due to the different biological origin, MBP being a marker of myelin sheath injury, and S-100, more probably, of astrocytic activity. PMID- 2581919 TI - Hb F-Tokyo or alpha 2G gamma 2 34(B16)Val----Ile, a silent gamma chain variant detected by reverse phase high performance liquid chromatography. AB - Hb F-Tokyo with a Valine----Isoleucine replacement at position gamma 34(B16) is a G gamma chain variant which was discovered by reverse phase chromatography as this method permitted the nearly complete separation of the three types of gamma chain. The chemical characterization was greatly facilitated by the use of a larger, preparative, HPLC column which allowed the isolation of sufficient quantities of the different gamma chains. PMID- 2581920 TI - Hb F-Pendergrass, an A gamma I variant with a Pro----Arg substitution at position gamma 36(C2). PMID- 2581921 TI - Pontamine sky blue: a counterstain for background autofluorescence in fluorescence and immunofluorescence histochemistry. AB - The stain pontamine sky blue (PSB) has been shown to reduce background autofluorescence in catecholamine fluorescence and immunofluorescence histochemical preparations. Using PSB as a counterstain on whole-mount stretch preparations of human mesenteric blood vessels, a medium dense noradrenergic nerve plexus is clearly revealed, which previously had been only partially visible because of background autofluorescence. Image analysis of nerve densities in whole-mount stretch preparations of guinea-pig arteries containing noradrenergic, substance P-, and vasoactive intestinal polypeptide (VIP)-positive nerve plexuses shows that PSB staining does not alter the specific neuronal fluorescence and that it improves image definition. PMID- 2581922 TI - Determination of DNA content in the nurse and follicle cells from wild type and mutant Drosophila melanogaster by DNA-Feulgen cytophotometry. AB - DNA replication patterns in the nurse and follicle cells of wild type and a female sterile mutant, fs(1)1304, of Drosophila melanogaster have been studied by DNA-Feulgen cytophotometry, using a cell dispersal technique that allowed the measurement of DNA amounts in individual nuclei from egg chambers of known developmental stages. DNA-Feulgen values associated with various ovarian nuclei from egg chambers at different stages of development were used to assess a base line DNA content for ovarian tissues and to estimate the extent of DNA replication in the nurse cells and follicle cells of growing and mature egg chambers. Our data show that both the nurse and follicle cells undergo multiple cycles of endonuclear DNA replication and that there may be selective amplification as well as underreplication by portions of the genome in these highly polyploid, ovarian cells. Alternative models are proposed to account for the DNA replication patterns observed. Comparisons of DNA-Feulgen levels in wild type ovarian nuclei with those found for the fs(1)1304 mutant and its heterozygote in the balanced stock fs/FM3, show that equivalent DNA levels are present in follicle cell nuclei from all three types of females. Nurse cell nuclei in the homozygous fs stock, however, fail to achieve the same high DNA levels observed in both fs/FM3 and wild type nurse cell nuclei. Although the nuclei of follicle cells in ovaries from fs/fs females appear morphologically like those surrounding egg chambers in wild type ovaries, nurse cell nuclei from mutant females show a more compacted organization of their chromatin than found for nurse cell nuclei from wild type ovaries at similar developmental stages. Our findings suggest that a major effect of the fs(1)1304 mutation may be on the coiling behavior of chromatin and the conformation of DNA-protein moieties in both nurse cell and follicle cell nuclei. These changes in chromatin structure apparently are manifest by perturbations in DNA replication patterns and normal gene function in these biosynthetically active cells. PMID- 2581924 TI - Rapid method for removal of inorganic mercury contained in methylmercury preparation using CM-Sephadex minicolumn. PMID- 2581923 TI - Microspectrophotometric quantitation of glycosaminoglycans in articular cartilage sections stained with Safranin O. AB - A new microspectrophotometric method was developed for quantitation of glycosaminoglycans with Safranin O dye in articular cartilage matrix. From histological sections molar extinction coefficient of Safranin O was determined and used to measure the dye content of the sections. The amount of glycosaminoglycans was determined with depth of bovine articular cartilage by both gas chromatography and thin layer chromatography to calculate the fixed negative charge content. Comparison between the results revealed that binding of Safranin O to glycosaminoglycan polyanions was stoichiometric and showed minimal nonspecific staining. The method provides an accurate technique for quantitation and localization of fixed negative charge content of glycosaminoglycans in the articular cartilage matrix. Specific enzyme digestions enable detection of separate glycosaminoglycans. PMID- 2581926 TI - The corallopyronins, new inhibitors of bacterial RNA synthesis from Myxobacteria. AB - From the culture broth of the myxobacterium, Corallococcus (Myxococcus) coralloides, three new antibiotics have been isolated: corallopyronin A, B and C. The compounds, which are chemically related to the recently discovered myxopyronins, act mainly on Gram-positive bacteria, with MIC values between 0.1 and 10 micrograms/ml, and only exceptionally or at much higher concentrations (MIC values; 100 and more micrograms/ml) on Gram-negatives. They do not inhibit eukaryotic organisms and show no toxicity for mice (sc). The corallopyronins appear to block specifically eubacterial RNA polymerase. PMID- 2581927 TI - Exercise-induced changes in blood zinc and related proteins in humans. AB - Effects of cycle ergometer exercise (approximately 75% maximum ventilatory O2 consumption for 30 min) on the concentrations of zinc and related proteins in erythrocytes and/or plasma were studied on 11 sedentary male students. Lower concentrations of total zinc and of zinc derived from carbonic anhydrase I type (CA-I) in erythrocytes were observed immediately after exercise, but they disappeared after 30 min of rest. The change in total zinc concentration in erythrocytes correlated well with that in CA-I concentration immediately after exercise, as well as after rest. The concentration of carbonic anhydrase II type (CA-II)-derived zinc did not vary substantially at any time. On the other hand, there were significant increases in the plasma concentrations of total zinc and of alpha 2-macroglobulin (alpha 2-MG)-bound zinc immediately after exercise, whereas no such effect was noted in albumin-bound zinc. A positive correlation was found between total zinc and alpha 2-MG concentrations in plasma immediately after exercise. In addition, the change in the activity of alkaline phosphatase, a zinc metalloenzyme, correlated well with that in the total zinc concentration in plasma. These results suggest that a brief physical exercise induces the movement of zinc into plasma. PMID- 2581925 TI - Receptor-mediated endocytosis of alpha 2-macroglobulin by principal cells in the proximal caput epididymidis in vivo. AB - Micropuncture techniques were used to study receptor-mediated endocytosis of alpha 2-macroglobulin bound to colloidal gold (alpha 2M-gold) by principal cells in the proximal caput epididymidis of control and efferent duct-ligated rats. The pathway of receptor-mediated endocytosis of alpha 2-macroglobulin-gold in vivo was similar to that which occurs in vitro. Alpha 2-macroglobulin-gold was taken up and internalized in coated pits and coated vesicles and was localized sequentially in uncoated vesicles (endosomes), tubular-vesicular structures, multivesicular bodies, and lysosomes. However, a 100-fold excess of alpha 2 macroglobulin did not displace the uptake of alpha 2-macroglobulin-gold in principal cells from control rats. In contrast, uptake of alpha 2-macroglobulin gold by principal cells from efferent duct-ligated rats was six-fold greater than in control rats, and could be displaced to control levels by a 100-fold excess of alpha 2-macroglobulin. It is suggested that the inability of a 100-fold excess of alpha 2-macroglobulin to displace uptake of alpha 2-macroglobulin-gold in control rats was due to the normal saturation of apparent alpha 2-macroglobulin receptors on principal cells. The effect of efferent duct ligation was to remove the high levels of endogenous alpha 2-macroglobulin, which depleted the receptors of alpha 2-macroglobulin, thereby allowing a higher uptake of alpha 2-macroglobulin-gold in the efferent duct-ligated rats. PMID- 2581928 TI - Effects of plasma- and cell-free perfusates on filtration coefficient of perfused canine lungs. AB - The filtration coefficient (Kf,c) of the microvessels in isolated dog lungs were studied for whole and diluted blood, whole and diluted plasma, Tyrode's solution, and Tyrode's plus dextran (4%, 63,000 mol wt) perfusates. When whole blood and plasma were diluted, Kf,c increased abruptly at a plasma protein concentration between 4 and 5 g/l, an effect which was not dependent on the erythrocyte mass. Both Tyrode's and Tyrode's plus dextran produced increases in Kf,c (60 and 30%, respectively). The difference in Kf,c measured between these latter perfusates was completely abolished when Kf,c were corrected for viscosity differences. Thus the pulmonary microvasculature responds similarly to the systemic circulation in that complete removal of plasma proteins from the perfusate increases Kf,c by 50%. This effect is independent of erythrocyte mass or colloid osmotic pressure of the perfusate, since perfusion with dextran solutions alone also increased Kf,c. PMID- 2581930 TI - The symbolic and object play of children with autism: a review. AB - The unique characteristics of autistic children's symbolic and object play are presented and discussed in the context of a literature review covering research since 1964. Several theoretical issues are highlighted: the relationship of play in facilitating language and cognition, play as an intervention, and play as an assessment tool. Difficulties in research methodology due to pooling autistic and schizophrenic subject are raised, as well as possible difficulties inherent in ignoring severity levels within the autistic population. The appropriateness of play therapy is questioned, and evidence is presented to provide encouragement for further inquiry into the study of autistic play. PMID- 2581931 TI - The utility of radioimmunoassay of serum human chorionic gonadotropin in the management of choriocarcinoma. PMID- 2581929 TI - Electrical properties of monolayers cultured from cells of human tracheal mucosa. AB - Dispersed isolated cells were obtained from human tracheal mucosa by digestion with collagenase. Up to 1.5 X 10(8) cells were obtained per trachea and showed up to 95% viability, as judged by trypan blue exclusion. When grown in culture, the cells formed monolayers after approximately 4 days. Electron microscopy of the monolayers revealed a polarized structure. An apical membrane, containing microvilli and a pronounced glycocalyx, was separated from a relatively unspecialized basolateral membrane by typical tight junctions. Monolayers grown on nucleopore filters showed resistances of 44-1,800 omega. cm2 and transepithelial potential differences of 0.1-7.6 mV. Short-circuit current (Isc) was increased by isoproterenol, prostaglandins E2 and F2 alpha, and bradykinin. The loop diuretic, bumetanide, reduced Isc when added to the basolateral (serosal) side but had no effect from the apical (mucosal) side of the monolayers. Furosemide and MK-196 also inhibited Isc. Mucosal amiloride inhibited Isc. Serosal amiloride or mucosal ouabain had no effect on Isc. Serosal ouabain brought Isc to zero after approximately 15 min. PMID- 2581933 TI - Control of Klebsiella pneumoniae nif mRNA synthesis. AB - Four probes, each specific for a single nif transcript, were used for an analysis of the regulation of nif mRNA synthesis. Transcription of the nifLA operon was repressed by NH4+ but not by amino acids, O2, or temperatures above 37 degrees C. The nifA gene product was required for the activation of transcription of the other nif operons but not nifLA. Synthesis of the other nif transcripts was rapidly turned off by the addition of O2, NH4+, serine, or glutamine. These regulatory effects required the nifL product. However, the nifL product was not required for the cessation of synthesis of these transcripts at elevated temperatures. PMID- 2581932 TI - Promoter mapping and transcriptional regulation of the iron assimilation system of plasmid ColV-K30 in Escherichia coli K-12. AB - The promoter of the high-affinity iron assimilation system coded in an approximately 8-kilobase-pair segment of the large Escherichia coli plasmid ColV K30 was localized to a 0.7-kilobase HindIII-SalI fragment by in vitro runoff transcription. By an S1 nuclease protection assay, with in vitro-transcribed RNA and total in vivo-synthesized RNA, the major start site for transcription was mapped within this fragment and found to be identical in vitro and in vivo. A minor initiation site was located about 50 base pairs upstream from the major site. DNA sequencing of the HindIII-SalI fragment revealed the presence of two promoter-like structures within an extremely AT-rich region with transcriptional initiation sites at 30 and about 80 base pairs upstream from the initiation codon for the first structural gene. Numerous potential secondary structures were found in the DNA sequence around the major promoter. The major transcriptional start site was determined precisely by sequencing the 5' end of in vitro-transcribed RNA. The effect of iron on both the level of specific RNA, as determined by a quantitative S1 nuclease mapping assay, and on beta-galactosidase activity in a iucA'-'lacZ protein fusion, showed that the aerobactin operon is regulated at the transcriptional level. The iron-regulatory sequences are contained within a 152 base-pair Sau3A fragment of the promoter region. PMID- 2581935 TI - Effects of light, oxygen, and substrates on steady-state levels of mRNA coding for ribulose-1,5-bisphosphate carboxylase and light-harvesting and reaction center polypeptides in Rhodopseudomonas sphaeroides. AB - The mRNA levels specific for ribulose-1,5-bisphosphate carboxylase, light harvesting I polypeptides alpha and beta, and reaction center polypeptides L and M were assayed by use of a series of DNA probes specific for each cognate mRNA. Both the steady-state amounts and sizes of the specific mRNAs were measured as a function of the light intensity incident to the culture, the presence or absence of oxygen, and the type of substrate present in the growth medium. Northern hybridization revealed at least two and possibly three transcripts for ribulose 1,5-bisphosphate carboxylase. The cellular level of mRNA specific for ribulose 1,5-bisphosphate carboxylase increased in consort with enzyme activity as a function of both light intensity and reducing state of the substrate. Neither mRNA nor enzyme activity was detectable in aerobically grown cells. For the light harvesting I and reaction center polypeptides there exist two transcripts, the larger of which appears to be a polycistronic mRNA possessing information for all four polypeptides and a smaller transcript specific for only the alpha and beta polypeptides of the light-harvesting I complex. The regulation of each of these mRNAs was affected by light and oxygen, but was not significantly affected by the oxidation-reduction state of the substrate. PMID- 2581936 TI - The correlation of chemical and osmotic forces in biochemistry. PMID- 2581937 TI - A new homogeneous enzyme immunoassay. Its application to measurement of alpha fetoprotein. AB - A rapid and sensitive homogeneous enzyme immunoassay (homogeneous EIA) was developed for determination of serum proteins such as alpha-fetoprotein (AFP). There are two assay systems, one is a competitive system including horseradish peroxidase (HRP)-labeled antigen, antibody and substrate, and the other is a non competitive system including HRP-labeled antibody and substrate. When the aggregate was formed through the binding of HRP-labeled AFP and anti-AFP antibody or through the binding of HRP-labeled anti-AFP antibody and AFP, HRP of the aggregates, as compared with HRP of free conjugates, exhibited marked activity in the presence of 35 mM H2O2. The extent of stimulation of HRP activity depended on the amount of AFP. This new assay method is very simple and sensitive, and can be used for the determination of any kind of protein, hormone, or drug. PMID- 2581934 TI - Polyadenylated, noncapped RNA from the archaebacterium Methanococcus vannielii. AB - Polyadenylated [poly(A)+] RNA molecules have been isolated from Methanococcus vannielii by oligodeoxythymidylate-cellulose affinity chromatography at 4 degrees C. Approximately 16% of the label in RNA isolated from cultures allowed to incorporate [3H]uridine for 3 min at 37 degrees C was poly(A)+ RNA. In contrast, less than 1% of the radioactivity in RNA labeled over a period of several generations was contained in poly(A)+ RNA molecules. Electrophoretic separation of poly(A)+ RNA molecules showed a heterogeneous population with mobilities indicative of sizes ranging from 900 to 3,000 bases in length. The population of poly(A)+ RNA molecules was found to have a half-life in vivo of approximately 12 min. Polyadenylate [poly(A)] tracts were isolated by digestion with RNase A and RNase T1 after 3' end labeling of the poly(A)+ RNA with RNA ligase. These radioactively labeled poly(A) oligonucleotides were shown by electrophoresis through DNA sequencing gels to average 10 bases in length, with major components of 5, 9, 10, 11, and 12 bases. The lengths of these poly(A) sequences are in agreement with estimates obtained from RNase A and RNase T1 digestions of [3H]adenine-labeled poly(A)+ RNA molecules. Poly(A)+ RNA molecules from M. vannielii were labeled at their 5' termini with T4 polynucleotide kinase after dephosphorylation with calf intestine alkaline phosphatase. Pretreatment of the RNA molecules with tobacco acid pyrophosphatase did not increase the amount of phosphate incorporated into poly(A)+ RNA molecules by polynucleotide kinase, indicating that the poly(A)+ RNA molecules did not have modified bases (caps) at their 5' termini. The relatively short poly(A) tracts, the lack of 5' cap structures, and the instability of the poly(A)+ RNA molecules isolated from M. vannielii indicate that these archaebacterial poly(A)+ RNAs more closely resemble eubacterial mRNAs than eucaryotic mRNAs. PMID- 2581938 TI - Monoclonal antibodies to human protein C: effects on the biological activity of activated protein C and the thrombin-catalyzed activation of protein C1. AB - Thirteen monoclonal antibodies designated as MFC-1 to MFC-13 were obtained from hybridoma cells cloned after the fusion of mouse myeloma cells with spleen cells of mice immunized with purified human protein C. Studies were made to determine where the antibodies bound to the molecule of protein C and whether they affected the biological actions of protein C. By using the immunoblotting technique, six of these antibodies were shown to bind to the light chain of protein C, and five to the heavy chain of protein C and also activated protein C. The remaining two antibodies bound to neither the light chain nor the heavy chain, though both antibodies bound to the intact protein C. Antibodies specific for the light chain did not bind to the gamma-carboxyglutamic acid-domain. Two of the antibodies specific for the heavy chain (MFC-13 and -1) inhibited the amidolytic activity of activated protein C. The MFC-13 also inhibited the activity of bovine activated protein C, but not that of human Factor IXa, Factor Xa, or thrombin. In addition to these two antibodies, another one for the heavy chain (MFC-10) and two antibodies for the light chain (MFC-9 and -11) inhibited the inactivation of Factor Va by human activated protein C. One of the antibodies which inhibited the enzyme activity (MFC-1) blocked the inhibition of activated protein C by protein C inhibitor. Another one for the heavy chain (MFC-5) inhibited the activation of protein C by thrombin regardless of the presence or absence of thrombomodulin. Based on these results, we have established the positions of some monoclonal antibody-binding sites on the protein C molecule. PMID- 2581939 TI - The structural relation between the antigenic determinants to monoclonal antibodies and binding sites to rat brain synaptosomes and GT1b ganglioside in Clostridium botulinum type C neurotoxin. AB - The inhibition of the binding of 125I-labeled Clostridium botulinum type C neurotoxin to synaptosomes by unlabeled toxin indicated that there were two kinds of receptors on the synaptosomal membrane. The dissociation constants (Kd) were calculated as 79 pM and 35 nM from the concentration of unlabeled toxin that induced half-displacement of bound 125I-toxin. These values agree satisfactorily with the values obtained from direct binding experiments (Agui, T, Syuto, B., Oguma, K., Iida, H., & Kubo, S. (1983) J. Biochem. 94, 521-527). The inhibition of the binding of 125I-toxin to synaptosomes and N-acetylneuraminyl(alpha 2 3)galactosyl(beta 1-3)N-acetylgalactosaminyl(beta 1-4) [N-acetylneuraminyl(alpha 2-8) N-acetylneuraminyl(alpha 2-3)]galactosyl(beta 1-4)glucosyl(beta 1-1)ceramide (GT1b) by unlabeled heavy chain indicated that heavy chain facilitates the binding of toxin to synaptosomes and GT1b. The synaptosomal and heavy chain complex Kd values were estimated as 12 nM and 24 microM. Monoclonal antibodies C 9 and CA-12 recognized the binding sites to GT1b and synaptosomes, respectively. Antigenic determinants against the two antibodies are presumably partially overlapping, and the overlapping area seems to be essential to the reaction between toxin and C-9 antibody. PMID- 2581940 TI - A comparative study of tyrosine 3-monooxygenase from rat adrenal and brainstem. AB - Spleen cells from a CBF1 (BALB/c X C57BL/6) mouse immunized with rat tyrosine 3 monooxygenase were fused with NS-1 mouse myeloma cells. From 188 hybrid cells, 2 stable clones secreting anti-tyrosine 3-monooxygenase antibody were obtained. Antibody from one clone was coupled to CNBr-activated Sepharose 4B and the monoclonal antibody-Sepharose was shown to be very useful for isolating rat tyrosine 3-monooxygenase from crude preparations. Analyses by monoclonal antibody chromatography followed by SDS-polyacrylamide gel electrophoresis and by gel filtration revealed that tyrosine 3-monooxygenases from nerve cell bodies, nerve terminals, and adrenal medullae were indistinguishable with respect to their molecular structures. However, there were serious differences in the catalytic properties between the enzymes from the brain tissues and adrenal medullae, although there appeared to be no significant difference between the enzymes from nerve cell bodies and nerve terminals. The possibility that the activity of the enzyme may be strongly suppressed especially at the physiological pH in brain tissues is also discussed. PMID- 2581941 TI - Molecular properties of ECMA 2 and ECMA 3 antigens defined by monoclonal antibodies against embryonal carcinoma cells. AB - ECMA 2 and ECMA 3 antigens defined by two monoclonal antibodies are preferentially expressed in early embryonic cells of the mouse. The antigens were isolated from F9 embryonal carcinoma cells by detergent solubilization followed by indirect immunoprecipitation. Both antigens were glycoproteins, which, upon extensive pronase digestion, released the high-molecular-weight glycan (embryoglycan). The immunoprecipitation reactions were inhibited by the glycan, indicating that the two antigens were carried by it. Furthermore, binding of anti ECMA 2 antibody to the glycan was directly demonstrated by a modified Farr's assay. The antigenic determinant of ECMA 2 antigen was found to involve an alpha galactosyl residue, since alpha-galactosidase from coffee bean, but not other glycosidases, abolished the antigenic activity. Serological experiments indicated that ECMA 2 antigen is different from other alpha-galactosyl antigens, namely blood group B and P1 antigens and an antigen defined by antibodies in the sera of patients with ovarian germ cell tumors. PMID- 2581942 TI - Inductive effects of prostaglandins on alkaline phosphatase in osteoblastic cells, clone MC3T3-E1. AB - The effects of prostaglandins (PGs) on the induction of alkaline phosphatase (ALP) were investigated in osteoblastic clone MC3T3-E1 cells cultured in serum free medium. Prostaglandin E2 (PGE2) stimulated ALP activity in the cells in a dose-dependent fashion with a maximal effect which was about twice that in the control cells at concentrations of 100-500 ng/ml. Actinomycin D and cycloheximide inhibited the stimulative effect of PGE2 on ALP activity in the cells. PGE2 induced and native ALPs in the cells were of the same type as that in adult mouse calvaria, being heat-labile, L-homoarginine- and levamisole-sensitive, and L phenylalanine-insensitive. Isobutyl methylxanthine (IBMX), a cAMP phosphodiesterase inhibitor, stimulated the inductive effect of PGE2 on ALP activity at 0.1 mM, at which concentration IBMX alone had little effect on the activity. PGE2 also increased the intracellular cAMP content in a dose-dependent fashion with a maximal effect at 100 ng/ml. PGE1, PGF1 alpha, and PGF2 alpha (primary PGs like PGE2) increased the activity. Our present results suggest that PGs stimulate the differentiation of osteoblasts and are involved in bone formation in vivo, as well as in bone resorption. PMID- 2581943 TI - RNA directed synthesis of catalytically active Drosophila sn-glycerol-3-phosphate dehydrogenase in Xenopus oocytes. AB - Xenopus laevis oocytes injected with poly(A)+ RNA isolated from Drosophila melanogaster direct the synthesis of catalytically active glycerol-3-phosphate dehydrogenase (NAD+) (EC 1.1.1.8). The de novo synthesized enzyme reflects the electrophoretic properties appropriate to the stock of flies from which the injected RNA was isolated and is electrophoretically distinct from endogenous Xenopus activity. Immunoprecipitation of 35S-labeled translation products has demonstrated two immunologically related proteins with molecular masses of 32- and 34kDa which are encoded by two separate mRNA molecules. The 32-kDa protein is identical in size and charge properties to the protein purified from the fly and possesses the catalytic activity observed in the Xenopus translational assay. Poly(A)+ RNA isolated from a strain of flies bearing a CRM- null mutation at the GPDH locus does not contain translatable RNA for the 32-kDa protein. These results suggest that the two immunologically related proteins are the translational products of two separate transcripts derived from either two related loci or from differential transcription and/or processing of the same genetic locus. PMID- 2581944 TI - Organization of a type I keratin gene. Evidence for evolution of intermediate filaments from a common ancestral gene. AB - The genomic structure of the mouse 59-kDa keratin gene, a Type I intermediate filament (IF) gene is presented. A comparison of the organization of this gene with that of the human 67-kDa keratin, a Type II IF gene, and hamster vimentin, a Type III IF gene, suggests a common evolutionary origin for Type I, II, and III IF genes. Most introns in these three types of IF genes occur at similar positions within the region encoding sequences predicted to form coiled-coils, but do not delineate structural subdomains. Interestingly though, most of the introns interrupt at or near the beginning of the characteristic 7-residue (heptad) repeat of sequences which form the coiled-coil. These data suggest that the three types of IF genes arose from a common ancestor which may have been assembled from smaller units containing multiple heptad repeats. Subsequent duplication events may then have formed the three known alpha-helical types and each of their various members. PMID- 2581945 TI - Characterization of an RNase P activity from HeLa cell mitochondria. Comparison with the cytosol RNase P activity. AB - A ribonuclease P-like activity was partially purified from HeLa cell mitochondria by DEAE-cellulose and octyl-Sepharose chromatography. RNase P-like activity can be quantitatively recovered from intact mitochondrial preparations treated with micrococcal nuclease, strongly suggesting that the enzyme is localized within the organelles. Mitochondrial RNase P (mtRNase P) cleaves the precursor to Escherichia coli suppressor tRNATyr at the same site as E. coli RNase P, producing the mature 5'-end of tRNATyr. The sensitivity of mtRNase P to pretreatment with nucleases or Pronase indicates that the enzyme has essential RNA and protein components. Although the ionic requirements of mtRNase P are similar to those of the RNase P activity isolated from the post-mitochondrial cytosol fraction, the chromatographic properties of mtRNase P are distinct. Mitochondrial RNase P is probably a part of the mitochondrial RNA processing machinery of mammalian mitochondria, being responsible for the endonucleolytic cleavage of the RNA transcripts at the 5'-side of the tRNA sequences. PMID- 2581946 TI - Phosphoribosylpyrophosphate synthesis from glucose decreases during amino acid starvation of human lymphoblasts. AB - When cultured human lymphoblasts are starved 3 h for an essential amino acid, rates of purine nucleotide synthesis decrease markedly because of a decrease in the intracellular phosphoribosylpyrophosphate concentration (Boss, G.R., and Erbe, R.W. (1982) J. Biol. Chem. 257, 4242-4247; Boss, G. R. (1984) J. Biol. Chem. 259, 2936-2941). In amino acid-starved cells, glucose transport was not changed, whereas total glucose consumption and lactate production decreased by approximately 25 and 10%, respectively. Carbon flow through the oxidative pentose phosphate pathway, measured by 14CO2 release from [1-14C]glucose, decreased by 18% during amino acid starvation. However, kinetic studies of ribulose-5 phosphate 3-epimerase and phosphoriboisomerase suggested that the ribulose 5 phosphate produced by this pathway is converted mostly to xylulose 5-phosphate instead of to ribose 5-phosphate so that this pathway produces little phosphoribosylpyrophosphate. The activity of the nonoxidative pentose phosphate pathway, measured by high performance liquid chromatography following the incorporation of [1-14C]glucose into phosphoribosylpyrophosphate, ATP, and GTP, decreased by approximately 55% during amino acid starvation. None of the enzymes of either pathway changed in specific activity during amino acid starvation. We conclude that the nonoxidative pentose phosphate pathway is the major source of phosphoribosylpyrophosphate for purine nucleotide synthesis and that this pathway is regulated by a metabolite which changes in concentration during amino acid starvation. PMID- 2581947 TI - The enzymatic conversion of 3'-phosphate terminated RNA chains to 2',3'-cyclic phosphate derivatives. AB - The enzyme, RNA cyclase, has been purified from cell-free extracts of HeLa cells approximately 6000-fold. The enzyme catalyzes the conversion of 3'-phosphate ends of RNA chains to the 2',3'-cyclic phosphate derivative in the presence of ATP or adenosine 5'-(gamma-thio)triphosphate (ATP gamma S) and Mg2+. The formation of 1 mol of 2',3'-cyclic phosphate ends is associated with the disappearance of 1 mol of 3'-phosphate termini and the hydrolysis of 1 mol of ATP gamma S to AMP and thiopyrophosphate. No other nucleotides could substitute for ATP or ATP gamma S in the reaction. The reaction catalyzed by RNA cyclase was not reversible and exchange reactions between [32P]pyrophosphate and ATP were not detected. However, an enzyme-AMP intermediate could be identified that was hydrolyzed by the addition of inorganic pyrophosphate or 3'-phosphate terminated RNA chains but not by 3'-OH terminated chains or inorganic phosphate. 3'-[32P](Up)10Gp* could be converted to a form that yielded, (Formula: see text) after degradation with nuclease P1, by the addition of wheat germ RNA ligase, 5'-hydroxylpolynucleotide kinase, RNA cyclase, and ATP. This indicates that the RNA cyclase had catalyzed the formation of the 2',3'-cyclic phosphate derivative, the kinase had phosphorylated the 5'-hydroxyl end of the RNA, and the wheat germ RNA ligase had catalyzed the formation of a 3',5'-phosphodiester linkage concomitant with the conversion of the 2',3'-cyclic end to a 2'-phosphate terminated residue. PMID- 2581948 TI - Molecular cloning of cDNA sequences for rat alpha 2-macroglobulin and measurement of its transcription during experimental inflammation. AB - Poly(A)+ RNA enriched in alpha 2-macroglobulin (alpha 2M) mRNA isolated from livers of rats 18 h after injection of turpentine was used for the synthesis of double-stranded cDNA. The double-stranded cDNA was inserted into the PstI site of the plasmid pBR322 by oligo(dG)-oligo(dC)-tailing technique. Clones containing sequences complementary to alpha 2M mRNA were selected by differential colony hybridization using 32P-labeled poly(A)+ RNA and [32P]cDNA from livers of control and turpentine-treated rats and subsequent hybrid-selected translation. The isolated p alpha 2M1 clone had an insert of 657 base pairs. DNA sequence analysis revealed a homology of about 80% to human alpha 2M. Northern analysis showed that the alpha 2M mRNA from rat liver is about 5600 bases in length. The alpha 2M cDNA was used to measure the in vitro transcription of the alpha 2M gene in isolated nuclei. A 4-fold increase in alpha 2M gene activity was found 14 h after turpentine administration. We conclude that alpha 2M transcription is induced during inflammation. PMID- 2581949 TI - DNA primase-DNA polymerase alpha from simian cells. Modulation of RNA primer synthesis by ribonucleoside triphosphates. AB - DNA primase-DNA polymerase alpha, purified 53,000-fold from CV-1 cells, synthesized predominantly (p)ppA(pA)6-primed DNA on a poly(dT) template. About 80% of the RNA primers synthesized on an M13 DNA template were (p)ppA/G(pN)5-7, and 20% were (p)ppA/G(pN)0-4. RNA primer size was determined by gel electrophoresis after removing nascent DNA with phage T4 DNA polymerase 3'-5' exonuclease, leaving a single dNMP at the 3'-end of the RNA primer, and the terminal 5'-(p)ppN residue was determined by "capping" with [alpha-32P]GTP using vaccinia guanylyl-transferase. The processivity of DNA synthesis initiated by de novo synthesis of RNA primers was the same as that initiated on pre-existing RNA primers (10-15 dNMPs), although initiation on pre-existing primers was strongly preferred. Primers always began with A or G, even at high levels of CTP or UTP, although the ratio of A to G varied from 4:1 to 1:1 depending on the relative concentrations of ATP and GTP in the assay. ATP and GTP had no effect on primer length, but the fraction of shorter RNA primers increased 2-fold with higher concentrations of CTP or UTP. Nearest-neighbor analysis revealed a preference for purine ribonucleotides at RNA covalently linked to the 5'-end of DNA (RNA-p-DNA) junctions, and increasing the concentration of a single rNTP increased slightly its presence at RNA-p-DNA junctions. Thus, the base composition and size of RNA primers synthesized by DNA primase-DNA polymerase alpha is modulated by the relative concentrations of ribonucleoside triphosphates. PMID- 2581950 TI - The amino acid sequence of a crystal protein from Bacillus thuringiensis deduced from the DNA base sequence. AB - We have determined the nucleotide sequence of a 4222-base segment of DNA which contains the promoter, the coding region, and the terminator of a crystal protein gene cloned from a Bacillus thuringiensis plasmid. A sequence of 1176 amino acids encoding a Mr 133,500 peptide was deduced from the single open reading frame. This protein-coding region was analyzed for codon usage, predicted hydropathy, and predicted secondary structure. Examination of the base sequence revealed the presence of several inverted and direct repeats located in both the coding and noncoding regions. S1 nuclease mapping was used to locate the transcription termination point at a site following a potentially very stable stem-and-loop structure. PMID- 2581951 TI - Adenine nucleotide and phosphate transport systems of mitochondria. Relative location of sulfhydryl groups based on the use of the novel fluorescent probe eosin-5-maleimide. AB - Eosin-5-maleimide is impermeable to the inner mitochondrial membrane, exhibiting essentially no reactivity with matrix glutathione or with beta-hydroxybutyrate dehydrogenase located on the matrix surface of the inner membrane. In intact mitochondria, eosin-5-maleimide is unreactive with the ADP/ATP antiporter even under conditions which promote maximal labeling by N-[3H]ethylmaleimide (i.e., ADP present). However, eosin-5-maleimide readily labels the ADP/ATP antiporter in "inverted" inner membrane vesicles even in the presence of N-ethylmaleimide. Labeling is prevented if the vesicles are prepared from mitochondria pretreated with carboxyatractyloside. In contrast to the ADP/ATP antiporter, essential sulfhydryl groups of the Pi/H+ symporter are accessible to eosin-5-maleimide in intact mitochondria with optimal inhibition of phosphate transport being observed at 25 degrees C. Eosin-5-maleimide also prevents labeling of the Pi/H+ symporter by N-[3H]ethylmaleimide. These results show that essential sulfhydryl groups of the ADP/ATP antiporter and the Pi/H+ symporter have differing reactivities and locations in functionally intact mitochondria. With respect to eosin-5-maleimide, sulfhydryl groups of the ADP/ATP carrier occur in two distinct classes, both of which are inaccessible in intact mitochondria. Only one class, depending on conditions, can be exposed in submitochondrial particles. In contrast, sulfhydryl group(s) of the Pi/H+ symporter behave as a single reactive class which is readily accessible in mitochondria at 25 degrees C. PMID- 2581953 TI - Monoclonal antibodies to bovine milk lipoprotein lipase. Evidence for proteolytic degradation of the native enzyme. AB - Lipoprotein lipase was purified from bovine skim milk by chromatography on heparin-Sepharose. Polyacrylamide gel electrophoresis showed a single protein with an apparent molecular weight of 55,000 in the trailing edge of the elution profile; fractions in the leading edge contained additional proteins with molecular weights of 36,000 and 18,000-22,000. Nine monoclonal antibodies were prepared against the 55,000-dalton protein. By immunoblotting, we show that the Mr = 18,000-22,000 components share common antigen determinants with the 55,000 dalton protein, suggesting that they represent proteolytic degradation products. Incubation of partially purified lipoprotein lipase for 24 h at 37 degrees C results in breakdown of the 55,000-dalton protein with concomitant enrichment in lower Mr components; the proteolytic activity is prevented by incubating the milk with phenylmethane, sulfonyl fluoride prior to chromatography on heparin Sepharose. This study shows the presence of milk proteases which co-purify and degrade lipoprotein lipase. We suggest that this degradation could account for part of the known instability of the enzyme. PMID- 2581952 TI - Identification and differential expression of two forms of regulatory subunits (RII) of cAMP-dependent protein kinase II in Friend erythroleukemic cells. Differentiation and 8-bromo-cAMP elicit a large and selective increase in the rate of biosynthesis of only one type of RII. AB - The concentration of regulatory subunits (R) of type II cAMP-dependent protein kinase increased 4- to 5-fold when Friend erythroleukemic cells were either grown in medium containing 0.5 mM 8-bromo-cAMP and 0.2 mM methylisobutylxanthine or stimulated to differentiate. Two species of RII with apparent Mr values of 54,000 (RII-54) and 52,000 (RII-52) are expressed in Friend cells. Both forms of RII were (a) covalently labeled with 8-N3-[32P]cAMP, (b) phosphorylated by the catalytic subunit of protein kinase II, and (c) complexed by polyclonal anti-RII IgGs. RII-52 and RII-54 were not interconverted by phosphorylation or dephosphorylation. A monoclonal antibody that recognizes an internal site in RII resolved the two cAMP-binding proteins by preferentially binding RII-54. The structural diversity suggested by the monoclonal antibody experiment was further examined by comparing two-dimensional maps of tryptic peptides obtained from metabolically labeled [( 35S]met) RII-52 and RII-54. Groups of 35S-labeled peptides that were either uniquely derived from RII-54 or obtained only from RII 52 were readily distinguished, thereby demonstrating that Friend cells produce two separate and distinct forms of type II cAMP-binding subunits. The relative rate of synthesis of RII-52 increased 12- to 14-fold during erythroid differentiation and treatment with 8-bromo-cAMP, while the rate of RII-54 synthesis either declined slowly or was unchanged. Thus, two homologous forms of RII are subject to different modes of physiological (differentiation) and pharmacological (chronic 8-Br-cAMP) regulation, and the accumulation of total RII observed in the present and previous (Schwartz, D. A., and Rubin, C. S. (1983) J. Biol. Chem. 258, 777-784) studies results from a selective increase in the rate of biosynthesis of RII-52. PMID- 2581954 TI - Purification and functional reconstitution of the voltage-sensitive sodium channel from rabbit T-tubular membranes. AB - The voltage-sensitive sodium channel has been purified from rabbit T-tubular membranes and reconstituted into defined phospholipid vesicles. Membranes enriched in T-tubular elements (specific [3H]nitrendipine binding = 41 +/- 9 pmol/mg of protein, n = 7) were isolated from fast skeletal muscle. After solubilization with Nonidet P-40, the sodium channel protein was purified to greater than 95% of theoretical homogeneity based on the specific activity of [3H]saxitoxin binding. Two subunits of Mr approximately 260,000 and 38,000 were found; these bands co-distributed with the peak of [3H]saxitoxin binding on sucrose gradients. The purified protein was reconstituted into egg phosphatidylcholine vesicles and retained the ability to gate specific 22Na+ influx in response to activation by batrachotoxin or veratridine. All activated fluxes were blocked by saxitoxin and tetrodotoxin. On sucrose gradients, the distribution of protein capable of functional channel activity paralleled the distribution of specific [3H]saxitoxin binding and of the Mr 260,000 and 38,000 components. The cation selectivity for the reconstituted, batrachotoxin-activated channel was Na+ greater than K+ greater than Rb+ greater than Cs+, with flux ratios of 1:0.13:0.02:0.008. Nine of 25 monoclonal antibodies raised against the rat sarcolemmal sodium channel cross-reacted with the rabbit T-tubular sodium channel in a solid-phase radioimmunoassay. Six of these antibodies showed specific binding to immunoblot transfers of T-tubular membrane proteins. Each labeled a single band at Mr approximately 260,000 corresponding in mobility to the large subunit of the sodium channel. PMID- 2581955 TI - The intragenic control region of the Xenopus 5 S RNA gene contains two factor A binding domains that must be aligned properly for efficient transcription initiation. AB - The in vitro recombination of deletion mutants of the Xenopus borealis somatic 5 S RNA gene allows construction of mutants containing substitutions of synthetic linker DNA for blocks of 9 or 10 nucleotides within the intragenic control region that binds transcription factor A. Two of the mutants containing exact linker replacements without insertion or deletion of nucleotides together alter 12 of 21 base pairs within the center of the control region. Both of these mutants bind factor A in an essentially normal pattern and support transcription, suggesting that a remarkable sequence variability can be tolerated in the center of the control region. The data obtained with these linker substitution mutants, along with data obtained previously with unidirectional deletion mutants, indicate that two short sequences at the boundaries of the control region serve as important recognition sites for the transcription factor. Additional closely related mutants containing slight deletions or insertions of form 2 to 10 base pairs do not bind factor A normally and do not support transcription in vitro. Thus, precise relative spacing of the boundaries of the control region is of critical importance for transcription. PMID- 2581956 TI - The primary structure of bovine cellular retinoic acid-binding protein. AB - The complete amino acid sequence of bovine adrenal gland cellular retinoic acid binding protein (CRABP) has been determined. The primary structure was established by analyses of cyanogen bromide fragments and peptides obtained by trypsin and Staphylococcus aureus protease digestions. The polypeptide chain of bovine CRABP comprises 136 amino acid residues. From partial sequence information, CRABP has been shown to be homologous to cellular retinol-binding protein, myelin protein P2, and the fatty acid-binding Z-protein. A comparison of the complete amino acid sequences of the members of this protein family, which also includes the rat intestinal fatty acid-binding protein, shows that CRABP is more similar to cellular retinol-binding protein and protein P2 than to the fatty acid-binding proteins. All five proteins are very similar in their NH2-terminal regions, suggesting that this part is important for a property common to the members of this protein family. This is the first report of a complete amino acid sequence of a CRABP. PMID- 2581958 TI - Control of peptide-chain initiation in rat skeletal muscle. Development of methods for preparation of native ribosomal subunits and analysis of the effect of insulin on formation of 40 S initiation complexes. AB - A method was developed for isolation of native ribosomal subunits from rat gastrocnemius muscle. Native 40 S subunits which were isolated by this method retained their associated nonribosomal proteins and consisted primarily of particles with equilibrium densities of 1.41 and 1.48 g/cm3. Based on the binding of radiolabeled Met-tRNAmeti, the 1.41 g/cm3 particle was identified as the 40 S initiation complex. Insulin deficiency in vivo resulting from either diabetes or fasting led to a 2-fold increase in 75 S monomers but had no effect on the numbers of native 40 and 60 S subunits or the relative distribution of the 1.41 and 1.48 g/cm3 particles. The rate of protein synthesis in perfused muscle preparations derived from insulin-deficient rats was reduced to about half the control value. Addition of insulin to the perfusate restored protein synthesis and 75 S monomers to control levels. The effect of insulin on protein synthesis was associated with a 1.5-fold increase in the amount of Met-tRNAmeti bound to the 1.41 g/cm3 particle. These findings identify formation of 40 S initiation complexes as a site of action of insulin on protein synthesis in skeletal muscle. PMID- 2581957 TI - Preparation and characterization of two monoclonal antibodies against different epitopes in Escherichia coli ribosomal protein L7/L12. AB - Two monoclonal antibodies with specificities for Escherichia coli 50 S ribosomal subunit protein L7/L12 were isolated. The antibodies and Fab fragments thereof were purified by affinity chromatography using solid-phase coupled L7/L12 protein as the immunoadsorbent. The two antibodies were shown to recognize different epitopes; one in the N-terminal and the other in the C-terminal domain of protein L7/L12. Both intact antibodies strongly inhibited polyuridylic acid-directed polyphenylalanine synthesis, ribosome-dependent GTPase activity, and the binding of elongation factor EF-G to the ribosome. Ratios of antibody to ribosome of 4:1 or less were effective in inhibiting these activities. Neither antibody prevented the association of ribosomal subunits to form 70 S ribosomes. The Fab fragments showed similar effects. PMID- 2581959 TI - Chemoattractant-elicited alterations of cAMP levels in human polymorphonuclear leukocytes require a Ca2+-dependent mechanism which is independent of transmembrane activation of adenylate cyclase. AB - The affinity of the chemoattractant receptor for N-formyl-methionyl-leucyl phenylalanine (fMet-Leu-Phe) on human polymorphonuclear leukocytes (PMNs) is regulated by guanine nucleotides, and chemoattractants stimulate increased intracellular cAMP levels in PMNs. Our data, however, indicate that this receptor does not activate membrane-bound adenylate cyclase via direct nucleotide regulatory protein (N) coupling but instead raises cAMP levels indirectly via a mechanism which appears to require Ca2+ mobilization. This conclusion is based on the following data: 1) prostaglandin E1 (PGE1) activated and alpha 2-adrenergic treatment inhibited adenylate cyclase activation in PMN plasma membranes; fMet Leu-Phe, however, neither activated nor inhibited adenylate cyclase in these membranes; 2) depletion of extracellular Ca2+ had no effect on isoproterenol and PGE1 elicited cAMP responses in intact PMNs while peak fMet-Leu-Phe and A23187 induced responses were reduced by approximately 50 and 80%, respectively; 3) 8 (N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate, a purported Ca2+ antagonist, caused almost complete inhibition of fMet-Leu-Phe and ionophore-induced cAMP responses in intact cells but had no effect on PGE1 and isoproterenol; 4) alpha 2 adrenergic agonists inhibited PGE1 but not chemoattractant- or A23187-elicited cAMP responses in intact PMNs; and 5) pretreatment of cells with a phosphodiesterase inhibitor (isobutylmethylxanthine) greatly potentiated the PGE1 and isoproterenol cAMP responses but nearly abolished the peak fMet-Leu-Phe response. Thus, chemoattractants appear to utilize a novel mechanism to raise cAMP levels which appear to require Ca2+ mobilization and could be mediated in part through a transient inhibition of phosphodiesterases. We suggest that stimulation of PMN functions by chemoattractants may utilize an N-coupled process to generate a Ca2+ signal which could in turn raise intracellular cAMP levels indirectly and thereby provide negative regulation. PMID- 2581960 TI - Cyclic GMP directly regulates a cation conductance in membranes of bovine rods by a cooperative mechanism. AB - Cyclic GMP causes the release of endogenous Ca2+ from rod outer segments, whose plasma membrane has been made permeable, or from isolated discs. Approximately 11,000 Ca2+ ions are released per disc at saturating concentrations of cyclic GMP. The velocity and the amplitude of the release of Ca2+ are dependent on the concentration of cyclic GMP. The maximal rate of the Ca2+ efflux is approximately 7 X 10(4) Ca2+ ions s-1 rod-1. The Ca2+ release by cyclic GMP is independent of light. The activation of the efflux occurred within a narrow range of the cyclic GMP concentration (30-80 microM) and does not obey a simple Michaelis-Menten scheme. Instead, the kinetic analysis of the Ca2+ efflux suggests that a minimum number of 2 molecules of cyclic GMP activates the ion conductance in a cooperative fashion. The release of Ca2+ by cyclic GMP requires a gradient of Ca2+ ions across the disc membrane. If the endogenous Ca2+ gradient is dissipated by means of the ionophore A23187, the release of Ca2+ by cyclic GMP is abolished. Ca2+ is released by analogues of cyclic GMP which are either modified at the 8 carbon position of the imidazole ring or by the deaza-analogue of cyclic GMP. Congeners of cyclic GMP which are modified at the ribose, phosphodiester, or pyrimidine portion of the molecule are ineffective. The hydrolysis of cyclic GMP by the light-regulated phosphodiesterase of rod outer segments is not a necessary condition for the Ca2+ release because 8-bromo-cyclic GMP, a congener resistant to hydrolysis, is a more powerful activator of the release than cyclic GMP itself. Ca2+ release by cyclic GMP is inhibited by organic and inorganic blockers of Ca2+ channels. The l-stereoisomer of cis-diltiazem blocks the release of Ca2+ at micromolar concentrations, whereas the d-form is much less effective. These results suggest that disc membranes contain a cationic conductance which is permeable to Ca2+ ions and which is regulated through the cooperative binding of at least 2 molecules of cyclic GMP to regulatory sites of the transport protein. By this mechanism, subtle changes in the concentration of cyclic GMP could promote large changes in the flux of Ca2+ ions across the disc membrane. PMID- 2581961 TI - Kinetic studies on dextransucrase from the cariogenic oral bacterium Streptococcus mutans. AB - The kinetic mechanism of dextransucrase was studied using the Streptococcus mutans enzyme purified by affinity chromatography to a specific activity of 36.9 mumol/min/mg of enzyme. In addition to dextran synthesis, the enzyme catalyzed sucrose hydrolysis and isotope exchange between fructose and sucrose. The rates of sucrose hydrolysis and dextran synthesis were partitioned as a function of dextran concentration such that exclusive sucrose hydrolysis was observed in the absence of dextran and exclusive dextran synthesis at high dextran concentrations. An analogous situation was observed with fructose-dependent partitioning of sucrose hydrolysis and fructose exchange. Steady state dextran synthesis and fructose isotope exchange kinetics were simplified by assay at dextran or fructose concentrations high enough to eliminate significant contributions from sucrose hydrolysis. This limited dextran synthesis assays to dextran concentrations above apparent saturation. The limitation was diminished by establishing conditions in which the enzyme does not distinguish between dextran as a substrate and product which allowed initial discrimination among mechanisms on the basis of the presence or absence of dextran substrate inhibition. No inhibition was observed, which excluded ping-pong and all but three common sequential mechanisms. Patterns of initial velocity fructose production inhibition and fructose isotope exchange at equilibrium were consistent with dextran synthesis proceeding by a rapid equilibrium random mechanism. A nonsequential segment was apparent in the exchange reaction between fructose and sucrose assayed in the absence of dextran. However, the absence of detectable glucosyl exchange between dextrans and the lack of steady state dextran substrate inhibition indicate that glucosyl transfer to dextran must occur almost exclusively through the sequential route. A review of the kinetic constants from steady state dextran synthesis, fructose product inhibition, and fructose isotope exchange showed a consistency in constants derived from each reaction and revealed that dextran binding increases the affinity of sucrose and fructose for dextransucrase. PMID- 2581962 TI - Cloned mouse ribonucleotide reductase subunit M1 cDNA reveals amino acid sequence homology with Escherichia coli and herpesvirus ribonucleotide reductases. AB - We have isolated and sequenced overlapping cDNA clones containing the entire coding region of mouse ribonucleotide reductase subunit M1. The coding region comprises 2.4 kilobases and predicts a polypeptide of 792 amino acids (Mr 90,234) which shows striking homology with ribonucleotide reductases from Escherichia coli and the herpesviruses, Epstein-Barr virus and herpes simplex virus. The homologies reveal three domains: an N-terminal domain common to the mammalian and bacterial enzymes, a C-terminal domain common to the mammalian and viral ribonucleotide reductases, and a central domain common to all three. We speculate on the functional basis of this conservation. PMID- 2581963 TI - Predominance of tyrosine phosphorylation of insulin receptors during the initial response of intact cells to insulin. AB - Anti-phosphotyrosine antibody and anti-insulin receptor antibody were used to study insulin-stimulated phosphorylation of the beta-subunit of the insulin receptor in [32P]orthophosphate-labeled Fao hepatoma cells. Without insulin, the receptor contained both phosphoserine and phosphothreonine and could be immunoprecipitated with anti-receptor antibody but not with the anti phosphotyrosine antibody. After incubation of these cells with insulin, both antibodies immunoprecipitated the phosphorylated receptor. The beta-subunit of the receptor precipitated with anti-phosphotyrosine antibody from cells stimulated with insulin (100 nM) for 1 min contained predominantly phosphotyrosine, whereas, after 10 min with insulin, the amounts of phosphotyrosine and phosphoserine were nearly equal. These results suggest that insulin-stimulated tyrosine phosphorylation preceded insulin-stimulated serine phosphorylation of the beta-subunit. Sequential immunoprecipitation of receptor with anti-phosphotyrosine antibody followed by precipitation of the remaining proteins with anti-receptor antibody suggests that insulin receptors which contain phosphoserine in the basal state are tyrosine phosphorylated more slowly than the dephosphorylated receptors or not at all after the addition of insulin. The beta-subunit of the insulin receptor was the major phosphorylated protein precipitated by the anti-phosphotyrosine antibody from insulin-stimulated Fao cells. These results confirm our notion that insulin initially stimulated tyrosine autophosphorylation and subsequently serine phosphorylation of the insulin receptor in intact cells and suggests that this sequence of reactions occurs faster on receptors that are dephosphorylated before the incubation with insulin. PMID- 2581964 TI - Amino acid sequences of mouse and human epidermal type II keratins of Mr 67,000 provide a systematic basis for the structural and functional diversity of the end domains of keratin intermediate filament subunits. AB - From the nucleotide sequences of specific cDNA clones, we present partial amino acid sequences (75-90% of the total) of 67-kDa type II keratin subunits expressed in terminally differentiating mouse and human epidermis. Analysis of the sequence information reveals that their secondary structures conform to the pattern common for all intermediate filament (IF) subunits. Together with the previously published sequence of the mouse 59-kDa type I keratin (Steinert, P. M., Rice, R. H., Roop, D. R., Trus, B. L., and Steven, A. C. (1983) Nature 302, 794-800) these data allow us to make comparisons between two keratins which are coexpressed in an epithelial cell type and which coassemble into the same IF. Moreover, these comparisons suggest a systematic plan for the general organization of the end domains of other keratin subunits. We postulate that each end domain consists of a set of subdomains which are distributed with bilateral symmetry with respect to the central alpha-helical domain. Type II (but not type I) keratins contain short globular sequences, H1 and H2, immediately adjacent to the central domain, that have been conserved in size and sequence and which account for most of the difference in mass between coexpressed type II and type I keratins. These are flanked by subdomains V1 and V2 that are highly variable in both length and sequence, often contain tandem peptide repeats, and are conspicuously rich in glycines and/or serines. At the termini are strongly basic subdomains (N and C, respectively) that are variable in sequence. Among keratins of a given type, their variability in mass appears to reside in the size of their V1 and V2 subdomains. However, coexpressed type I and type II keratins have generally similar V1 and/or V2 sequences. By virtue of the ease with which large portions of these subdomain sequences can be removed from intact keratin IF by limited proteolysis, we hypothesize that they lie on the periphery of the IF where they participate in interactions with other constituents of epithelial cells. PMID- 2581965 TI - A monoclonal antibody that recognizes the functional domain of Escherichia coli single-stranded DNA binding protein that includes the ssb-113 mutation. AB - We have isolated a monoclonal antibody against Escherichia coli single-stranded DNA binding protein (SSB) that recognizes the functional domain specified by the ssb-113 temperature-sensitive mutation, a domain which is distinct from the DNA binding site. Although the ssb-113 and ssb-1 mutations result in many similar phenotypic defects, they differ significantly in others, indicating that they affect different functional domains of the protein. Whereas the SSB-1 mutant protein is clearly defective in tetramer formation and is also unable to bind single-stranded DNA at nonpermissive temperatures, no similar in vitro defects have yet been found in the SSB-113 mutant protein. In fact, the only reported in vitro effect of the ssb-113 mutation on the protein is a slight increase in its helix destabilizing ability. Competition radioimmunoassays using a monoclonal antibody demonstrated that SSB-113 mutant protein, containing a single amino acid substitution at position 176 (the penultimate residue), did not compete with SSB while SSB-1 protein (with a single change at position 55) did compete with SSB. This analysis was refined by studies with a proteolysis fragment and with peptides derived from both SSB and SSB-113. The results indicate that the antibody recognizes a determinant near the COOH-terminal end of the protein and that the SSB-113 mutation lies within or very close to this determinant. PMID- 2581966 TI - Doxorubicin induces calcium release from terminal cisternae of skeletal muscle. A study on isolated sarcoplasmic reticulum and chemically skinned fibers. AB - In this study, we investigated the effect of the anticancer drug doxorubicin on Ca2+ fluxes of isolated highly purified sarcoplasmic reticulum fractions (longitudinal tubules and terminal cisternae (Saito, A., Seiler, S., Chu, A., and Fleischer, S. (1984) J. Cell Biol. 99, 875-885] and of chemically skinned skeletal muscle fibers of the rabbit. In terminal cisternae, doxorubicin inhibits Ca2+ uptake (IC50 at 0.5 microM) and increases 2.6-fold Ca2+-dependent ATPase rate (half-maximal activation at 3 microM) and unidirectional Ca2+ efflux (8-fold stimulation at 25 microM). On the contrary, doxorubicin is without effect on longitudinal tubules. In skinned muscle fibers, doxorubicin induces rapid and transient Ca2+ release, as measured by tension development (half-maximal stimulation at 6 microM), which is completely and reversibly inhibited by ruthenium red, a known inhibitor of Ca2+ release from isolated terminal cisternae. Doxorubicin has no effect on the sarcoplasmic reticulum Ca2+ pump and on the contractile apparatus of skinned muscle fibers. It is concluded that doxorubicin activates Ca2+ release from sarcoplasmic reticulum and opens a Ca2+ efflux pathway (Ca2+ channel) selectively localized in terminal cisternae. Doxorubicin might interact with Ca2+ channels involved in physiological Ca2+ release. PMID- 2581967 TI - Nucleotide sequence analysis of a cDNA encoding human ubiquitin reveals that ubiquitin is synthesized as a precursor. AB - Ubiquitin is a 76-amino acid protein whose sequence is highly conserved throughout evolution from invertebrates to mammals. It is both a cytoplasmic and nuclear protein. In the cytoplasm it is involved in ATP-dependent nonlysosomal proteolysis. In the nucleus, ubiquitin is conjugated to histone 2A and may play a role in regulation of chromatin structure and/or regulation of transcriptional activity. During attempts to identify a cDNA encoding somatomedin-C (insulin-like growth factor I) we screened a fetal human liver cDNA library with a mixture of 17 base oligonucleotides corresponding to a portion of the B chain of somatomedin C. One oligonucleotide of the mixture hybridized to two cDNAs encoding ubiquitin despite a 2-base pair mismatch. Nucleotide sequence analyses of the 350- and 516 base pair cDNAs revealed that they correspond to the same ubiquitin mRNA. The coding sequence of the 516-base pair cDNA begins at amino acid 5 of the ubiquitin sequence and encodes amino acids 5 through 76 of ubiquitin, an 80-amino acid carboxy-terminal extension, a 3' untranslated region, and a poly(A) tail. The finding that ubiquitin is synthesized as a precursor raises the possibility that the precursor sequence may be important in compartmentalization of ubiquitin or ubiquitin precursors. Analyses of ubiquitin mRNAs in poly(A) RNA extracted from human liver and various rat tissues reveals that there are three distinct mRNAs encoding ubiquitin in humans and four mRNAs in the rat. PMID- 2581968 TI - The induction of ribosome biosynthesis in a nonmitotic secretory tissue. AB - Many investigations of the biosynthesis of ribosomes have revealed that ribosome numbers increase with growth rate in a parallel fashion. However, we have now shown that there is also a need for active ribosome synthesis in a nonmitotic tissue which is induced to secrete. The paragonial glands of Drosophila melanogaster produce and secrete proteins that are found in the seminal fluid. Following even a single copulation event these glands are substantially reduced in size, but rapidly refill, synthesizing new secretion proteins (Chen, P.S. 1980) in Invertebrate Systems in Vitro (Kurstak, E., Maramorosch, K., and Dubendorfer, A., eds) pp. 303-313, Elsevier, Amsterdam) Anticipating that paragonial gland cells might require more ribosomes to accomplish this burst of protein synthesis, we injected 10-day-old adult male flies with either [32P] phosphate or [35S]methionine, allowed them to copulate (40 +/- 20 min after injection), and then measured the amounts of rRNA and ribosomal protein synthesis taking place with time. There is clearly a burst of ribosome synthesis starting as early as 30 min after copulation and declining after 6 h. This is evidenced by the coordinate accumulation of labeled rRNAs and ribosomal proteins. However, further experiments showed that there is no concomitant rise in the accumulation of ribosomal protein mRNAs. This suggests that these mRNAs are underutilized in the paragonial glands before copulation and more actively translated after copulation. A stimulation of translation of ribosomal proteins is then well coordinated with increased rRNA transcription, but an increase of ribosomal protein mRNAs is not coordinated with these events. Both the up- and down regulation of ribosome biosynthesis need not be coupled to cell growth or a specific developmental schedule, but rather may be due to the need for secretory protein synthesis. PMID- 2581969 TI - cDNA clones coding for the pro-alpha1(IV) chain of human type IV procollagen reveal an unusual homology of amino acid sequences in two halves of the carboxyl terminal domain. AB - We report the isolation and characterization of cDNA clones coding for part of the pro-alpha1(IV) chain of human type IV procollagen. A cDNA library was prepared from total RNA isolated from a cultured human tumor cell line, HT-1080, and screened with a cloned mouse cDNA coding for the pro-alpha1(IV) chain. The largest cDNA clone encoded for 185 amino acid residues of the -Gly-X-Y-sequence of the human pro-alpha1(IV) chain, all of the globular carboxyl-terminal domain, and the 3' noncoding region. The results provide the first complete sequence for the carboxyl-terminal globular portion of a type IV procollagen chain. A striking feature of the carboxyl-terminal globular domain was a homology between the first and second half of the structure. The homology involved all 12 cysteine residues, the spacing between the cysteine residues, and many adjacent amino acids. The results raised the possibility that evolution of the globular domain involved duplication of an ancestral sequence coding for about 100 amino acids, 6 of which were cysteine. The homology, however, was more apparent in the amino acid sequence than in the nucleotide sequence, and, therefore, the results suggested that the homology reflects selective pressure on the function of the protein more than conservation of the nucleotide sequences in the gene. The nucleotide sequences of the 3' noncoding region of the cDNAs contained four polyadenylation signals of AATAAA. Three or four of the polyadenylation signals were probably used in transcription, since one major and two minor smaller RNA species from human skin fibroblasts hydridized with the cDNAs. In further studies, sorted human chromosomes were used to locate the gene for the pro-alpha1(IV) chain on chromosome 13. PMID- 2581970 TI - Structure and expression of two human metallothionein-I isoform genes and a related pseudogene. AB - Three members of the human metallothionein-I gene family have been cloned and characterized. Two of the genes encode closely related but distinct metallothionein-I subtypes. Both of these genes are functional as shown by their transcription in cultured hepatoblastoma cells and by their ability to render transfected cells resistant to cadmium toxicity. The cotranscription of these nonallelic genes shows that the previously observed microheterogeneity of metallothionein-I protein preparations is due to the expression of distinct gene products. The third clone is incapable of encoding a typical metallothionein due to an early termination codon and two nonconservative amino acid replacements. This nonfunctional pseudogene retains introns. Evolutionary comparisons reveal conserved DNA sequences in both the coding and regulatory regions of these genes. PMID- 2581971 TI - New U1 RNA species found in Friend SFFV (spleen focus forming virus)-transformed mouse cells. AB - The U1 RNA species in 10 mouse cell lines were examined by two-dimensional polyacrylamide gel electrophoresis. Seven cell lines that were not infected by Friend spleen focus forming virus gave only one (I) or two (I and II) U1 RNA containing spots. However, two Friend cell lines (FVTCT and Friend 745a cells) gave three spots (I, II, and III) and another Friend cell line, K-1 cells, gave four spots (I, II, III, and IV). As a result of further separation and fingerprinting analysis of each spot, FVTCT and Friend 745a cells were found to contain U1a-1, U1b-1, -2, and -6 RNAs whereas K-1 cells were found to contain several U1 RNAs, which we call U1a-1 and -2, U1b-4, -5, and -6 RNAs. We determined the sequences of these seven U1 RNAs and found that mouse U1 RNAs had two basic sequences (U1a and -b). The nucleotide sequence of U1a-1 RNA was identical to that of rat U1a RNA, while U1a-2 RNA was one base different from U1a 1 RNA. Relative to U1a-1 RNA all of the U1b RNAs had five base substitutions and one additional base and were under-methylated in the center. U1b-6 RNA contained two base substitutions and one base addition in the 3'-terminal portion of U1b-1 RNA. U1b-2, -4, and -5 RNAs, which were observed only in Friend cells, each had an additional base substitution in the 5'-half of U1b-1 RNA. PMID- 2581973 TI - Coronary bypass for left main disease in patients over 70 years of age. AB - Seventy-one consecutive patients over 70 years of age underwent isolated coronary bypass surgery for left main coronary artery (LMCA) disease between September 1975 and December 1982. All patients had angina; 6% were in NYHA functional class II, 30% class III, and 64% class IV. Intravenous nitroglycerin was required in 25% of patients. Resting electrocardiogram was abnormal in 91% of patients and stress testing performed in 24 patients was positive in all. Degree of left main stenosis graded by diameter was 60 to 70% in 24% of patients and greater than 70% in 76%. In addition to left main stenosis 66% of patients had significant triple vessel disease. Left ventricular end diastolic pressure (LVEDP) was elevated in 69% of patients while ejection fraction (EF) was low only 24%, without correlation between high LVEDP and low EF. Mean number of bypass grafts per patient was 3.4 +/- 0.6. Hospital mortality was 7% and mean post-operative stay was 10.4 +/- 2.0 days. Stepwise multiple regression analysis of 12 variables identified only unstable angina requiring intravenous nitroglycerin as a significant predictor of hospital mortality (p less than 0.01). Follow-up was complete with a late cardiac mortality of 4.5%. Seventy-five percent of surviving patients assessed their quality of life as good at a mean follow-up of 26 months. Coronary bypass for LMCA disease in a non-selected elderly population can be performed with low operative mortality and marked improvement in quality of life. PMID- 2581972 TI - Pathological fractures of the cervical spine. Palliative surgical treatment. AB - Eleven patients with metastases in the cervical spine had operations for severe pain due to a pathological fracture which, in eight of the cases, was unstable. Conservative treatment had either failed or was unsuitable. In the first five patients internal fixation with tension band wires and bone grafts was supported by a halo-brace. The method has evolved to the use of posterior instrumentation with laminar wires from two levels above the lesion to two levels below. Stability is increased by the use of bone cement with or without bone autografts applied to one side of the spine. This technique enables the patient to get up within a few days of operation--a great advantage when life expectancy is limited. The operations were successful in all except one case. PMID- 2581974 TI - Discoidin I, an endogenous lectin, is externalized from Dictyostelium discoideum in multilamellar bodies. AB - Discoidin I, a soluble lectin synthesized by aggregating Dictyostelium discoideum and implicated in their adhesion to the substratum, is localized in multilamellar bodies both intracellularly and upon externalization. These structures also contain a glycoconjugate that binds discoidin I. The multilamellar bodies apparently serve to package the lectin for externalization, and may then gradually release it to function extracellularly. PMID- 2581975 TI - The microsporidian spore invasion tube. IV. Discharge activation begins with pH triggered Ca2+ influx. AB - The microsporidian spore extrusion apparatus activates with a calcium influx from Spraguea lophii spore wall/plasma membrane; this influx requires preconditioning with an extrasporular shift in medium pH to the alkaline in the presence of the polyanions mucin or polyglutamate. Undischarged S. lophii spores display calcium bound to the wall/plasma membrane with a characteristic calcium chlorotetracycline fluorescence; this fluorescence declines significantly during spore discharge. S. lophii spores do not discharge when spore wall/plasma membrane calcium is removed with EGTA. Extrasporular mucin or polyglutamate and a pH shift to the alkaline appear to be necessary preconditions for the triggering of the influx of spore wall/plasma membrane-bound 45Ca2+. Ionophore A-23187 also effectively activates spore discharge without other extrasporular polyanions. Micromolar concentrations of the calcium antagonists lanthanum or verapamil prevent spore discharge, and micromolar concentrations of calmodulin inhibitors chlorpromazine and trifluroperazine prevent spore discharge. Calmodulin, visualized with a calmodulin antibody and a peroxidase conjugate, is localized particularly on the plasma membrane and the polaroplast membranes of the extrusion apparatus. PMID- 2581976 TI - Outer plaque assembly and spore encapsulation are defective during sporulation of adenylate cyclase-deficient mutants of Saccharomyces cerevisiae. AB - Sporulation in diploid cells homozygous for the cyr1-2 mutation of the yeast Saccharomyces cerevisiae was examined. This mutation causes a defect in adenylate cyclase and temperature-sensitive arrest in the G1 phase of the mitotic cell cycle. The cyr1-2/cyr1-2 diploid cells were able to initiate meiotic divisions, but produced predominantly two-spored asci at the restrictive temperature. Temperature-sensitive period for production of two-spored asci was approximately 12 h after the transfer of cells to the sporulation medium. The levels of cAMP increased during this period in the wild type and cyr1-2/cyr1-2 diploid cells incubated at the permissive temperature, but remained at an extremely low level in the cyr1-2/cyr1-2 diploid cells incubated at the restrictive temperature. Dyad analysis of the cyr1-2 strain indicated that meiotic products were randomly included into ascospores. Fluorescent microscopy of the cyr1-2/cyr1-2 diploid cells incubated at the restrictive temperature revealed that individual haploid nuclei were enclosed in each of the two spores after meiosis. About half of the cyr1-2/cyr1-2 diploid cells entered normal meiosis 1 producing two normal spindle pole bodies with inner and outer plaques, and the other half entered abnormal meiosis 1 producing one normal spindle pole body and one defective spindle pole body without out plaque. At meiosis II, some cells contained a pair of normal spindle pole bodies and other cells contained pairs of normal and abnormal spindle pole bodies. PMID- 2581977 TI - Effect of taxol on secretory cells: functional, morphological, and electrophysiological correlates. AB - The effect of 0.5-1.0 microM taxol, a potent promoter of microtubule polymerization in vitro, was studied on the secretory activity of chromaffin cells of the adrenal medulla. Taxol was found to have a dual effect: the long term effect (after a 1-h incubation) of taxol was to induce almost complete inhibition of catecholamine release, whereas after a short incubation (10 min) a massive, nicotine-independent release of catecholamine was produced. From results obtained using the patch-clamp technique to study the Ca++-dependent K+ channels (Ic channels), it was possible to conclude that taxol probably provokes an augmentation of free [Ca++]i in the cytoplasm, values increasing from 10(-8) M at rest to several 10(-7) M. The increased spontaneous release of stored neurohormones and the increased frequency of opening of Ic channels occur simultaneously and could both originate from a rise of [Ca++]i upon taxol addition. Immunofluorescence and ultrastructural studies showed that 13-h taxol treatment of chromaffin cells led to a different distribution of secretory organelles, and also to microtubule reorganization. In treated cells, microtubules were found to form bundles beneath the cell membrane and, at the ultrastructural level, to be packed along the cell axis. It is concluded that in addition to its action on microtubules, the antitumor drug taxol has side effects on the cell secretory activity, one of them being to modify free [Ca++]i. PMID- 2581978 TI - Subunit structure of paired helical filaments in Alzheimer's disease. AB - The neurofibrillary tangles that occur in the brain in cases of senile dementia of the Alzheimer type contain a distinctive type of filament, the paired helical filament (PHF). We have developed a method for isolating the tangles postmortem in sufficient yield for structural study of PHFs by electron microscopy of negatively stained and shadowed preparations. This material shows the characteristic helical structure seen in sectioned embedded material. In addition, two striking fragmentation patterns are observed. (a) Some filaments show sharp transverse breaks at apparently random positions along the filament. (b) In a few PHFs one strand is missing for a variable length, whereas the other appears to maintain its structural integrity. The shadowed specimens show the PHF to be wound in a left-handed manner. These observations indicate that the PHF consists of subunits of very limited axial extent arranged along two left-handed helical strands. The visualization of the substructure within the PHFs is rather variable and a model building approach has therefore been adopted, which has allowed the main features seen in the images to be interpreted. The subunit appears to have at least two domains in a radial direction and an axial extent of less than 5 nm. The whole structure can best be described as a twisted ribbon and indeed alkali treatment does untwist PHFs to give flat ribbons. The nature of the proposed model makes it most unlikely that the PHF is formed by a simple collapse of normal cytoskeletal elements, such as neurofilaments. PMID- 2581979 TI - Elongation arrest is not a prerequisite for secretory protein translocation across the microsomal membrane. AB - Signal recognition particle (SRP) is a ribonucleoprotein consisting of six distinct polypeptides and one molecule of small cytoplasmic 7SL RNA. It was previously shown to promote the co-translational translocation of secretory proteins across the endoplasmic reticulum by (a) arresting the elongation of the presecretory nascent chain at a specific point, and (b) interacting with the SRP receptor, an integral membrane protein of the endoplasmic reticulum which is active in releasing the elongation arrest. Recently a procedure was designed by which the particle could be disassembled into its protein and RNA components. We have further separated the SRP proteins into four homogeneous fractions. When recombined with each other and with 7SL RNA, they formed fully active SRP. Particles missing specific proteins were assembled in the hope that some of these would retain some functional activity. SRP(-9/14), the particle lacking the 9-kD and 14-kD polypeptides, was fully active in promoting translocation, but was completely inactive in elongation arrest. This implied that elongation arrest is not a prerequisite for protein translocation. SRP receptor was required for SRP( 9/14)-mediated translocation to occur, and thus must play some role in the translocation process in addition to releasing the elongation arrest. PMID- 2581981 TI - Expression and assembly of the erythroid membrane-skeletal proteins ankyrin (goblin) and spectrin in the morphogenesis of chicken neurons. AB - The membrane-skeleton of adult chicken neurons in the cerebellum and optic system is composed of polypeptides structurally and functionally related to the erythroid proteins spectrin and ankyrin, respectively. Neuronal spectrin comprises two distinct complexes that share a common alpha subunit (Mr 240,000) but which have structurally distinct polymorphic subunits (beta' beta spectrin; Mr 220/225,000; gamma spectrin, Mr 235,000); the brain-specific form (alpha gamma spectrin or fodrin) and an erythrocyte-specific form (alpha beta' beta spectrin). Two structurally related isoforms of ankyrin have also been identified and are termed alpha (Mr 260,000) and beta (Mr 237,000) ankyrin. Immunofluorescence demonstrates that the variants of spectrin and ankyrin, respectively, have different distributions within neurons. On the one hand, alpha gamma spectrin and beta ankyrin are present throughout the neuron, in the perikaryon, dendrites, and axon, whereas alpha beta' spectrin and alpha ankyrin are localized exclusively in the perikaryon and dendrites where they are actively segregated from alpha gamma spectrin and other components of axonal transport. This asymmetric distribution of spectrin and ankyrin isoforms is established in distinct stages during neuronal morphogenesis. Early in cerebellar and retinal development, alpha gamma spectrin is expressed in mitotic cells. Subsequently beta ankyrin and alpha gamma spectrin are coexpressed in postmitotic cells and gradually accumulate on the plasma membrane in a uniform pattern throughout the neuron during the phase of cell growth. At the onset of synaptogenesis and the cessation of cell growth, their levels of synthesis decline sharply while the assembled proteins remained as stable membrane components. Concomitantly, there is a dramatic induction in the accumulation of alpha ankyrin and alpha beta' spectrin, whose assembly is limited to the plasma membrane of the perikarya and dendrites. These results demonstrate that two successive, developmentally regulated programs of ankyrin and spectrin expression and patterning on the plasma membrane are involved in the assembly of the spectrin-based asymmetry in the neuronal membrane-skeleton, and that their asymmetric distribution is actively maintained throughout the life of the neuron. PMID- 2581980 TI - Detachment of cells from culture substrate by soluble fibronectin peptides. AB - The synthetic cell attachment-promoting peptides from fibronectin (Pierschbacher, M. D., and E. Ruoslahti, 1984, Nature (Lond.)., 309:30-33) were found to detach cultured cells from the substratum when added to the culture in a soluble form. Peptides ranging in length from tetrapeptide to heptapeptide and containing the active L-arginyl-glycyl-L-aspartic acid (Arg-Gly-Asp) sequence had the detaching activity, whereas a series of different peptides with chemically similar structures had no detectable effect on any of the test cells. The Arg-Gly-Asp containing peptides caused detachment of various cell lines of different species and histogenetic origin. Studies with defined substrates showed that the active peptides could inhibit the attachment of cells to vitronectin in addition to fibronectin, indicating that vitronectin is recognized by cells through a similar mechanism as fibronectin. The peptides did not inhibit the attachment of cells to collagen. However, cells cultured on collagen-coated plastic for 24-36 h, as well as cells with demonstrable type I or type VI collagen in their matrix, were susceptible to the detaching effect of the peptides. These results indicate that the recognition mechanism(s) by which cells bind to fibronectinand vitronectin plays a major role in the substratum attachment of cells and that collagens may not be directly involved in cell-substratum adhesion. Since vitronectin is abundant in serum, it is probably an important component in mediating the attachment of cultured cells. The independence of the effects of the peptide on the presence of serum and the susceptibility of many different cell types to detachment by the peptide show that the peptides perturb an attachment mechanism that is intrinsic to the cells and fundamentally significant to their adhesion. PMID- 2581982 TI - Simple and rapid identification of phosphorylated peptides from bovine brain myelin basic protein by reversed-phase high-performance liquid chromatography. AB - The phosphorylation sites of the myelin basic protein from bovine brain were determined after phosphorylation with a cyclic 3':5'-phosphate-dependent protein kinase from the same source. Three phosphorylated peptides were selectively and rapidly separated, before and after dephosphorylation, by reversed-phase high performance liquid chromatography on a styrene 250 column under alkaline conditions. Partial sequencing of the peptides by automated Edman degradation revealed that the serine-115 residue located in the main encephalitogenic determinant of the protein was a phosphorylation site, in addition to the two phosphorylation sites established (threonine-34 and serine-55). PMID- 2581983 TI - Comparison of chromatographic characteristics of a series of homologous Bence Jones proteins during size-exclusion chromatography by high-performance liquid chromatography and by Sephadex. PMID- 2581984 TI - Gas chromatographic analysis of triethylenethiophosphoramide and triethylenephosphoramide in biological specimens. AB - Comprehensive pharmacokinetic studies could realise a greater potential for the antitumour agent triethylenethiophosphoramide (ThioTEPA), and these would be aided by the development of a selective and sensitive assay. After extraction of ThioTEPA and its metabolite, triethylenephosphoramide (TEPA), from plasma using Sep-Pak C18 cartridges, the compounds were separated by capillary chromatography, detected using a nitrogen detector and quantified by reference to an internal standard, hexaethylphosphoramide. The limits of sensitivity were 1-5 ng/ml. Analytical recoveries were 74 and 95%, for TEPA and ThioTEPA, respectively, in the therapeutic range. At similar concentrations, extents of protein binding, determined by ultrafiltration, were not significant. Preliminary investigations of the elimination of ThioTEPA show that drug loss occurs more quickly in mice than in humans and in both species the metabolite is extensively recycled. PMID- 2581985 TI - Simple purification procedure of rat alpha-fetoprotein by a combination of Cibacron Blue gel affinity chromatography and anion-exchange high-performance liquid chromatography. PMID- 2581986 TI - Determination of polycyclic aromatic hydrocarbons in environmental samples by high performance thin-layer chromatography and fluorescence scanning densitometry. AB - High performance thin-layer chromatography (HPTLC) with fluorescence scanning densitometry was used for the quantitative determination of polycyclic aromatic hydrocarbons in the soluble organic fraction of air particulate samples. A method using normalized emission response ratios was developed to determine sample identity and to test for peak homogeneity. To preserve the high sample throughput of HPTLC, the two-point calibration method was used for quantitation. The principal advantages of HPTLC as a screening technique for environmental samples are its low cost, methodological simplicity, high sample throughput, and the ability to analyze crude samples with a minimum amount of sample cleanup. PMID- 2581987 TI - Comparison of two techniques for detecting antibody to HBsAg during a hepatitis B vaccine study. AB - Two assays for the detection of antibody against hepatitis B surface antigen (anti-HBs) were compared. The first was a direct sandwich radioimmunoassay (RIA) which detects, in principle, antibody against any epitope of hepatitis B surface antigen (HBsAg). The second assay was an inhibition enzyme-linked immunosorbent assay (ELISA). In this assay a fixed amount of HBsAg which can be blocked by anti HBs is measured in a direct sandwich test. Prevaccination screening sera (n = 191) and follow-up sera obtained from high risk groups (n1 = 85; n2 = 41) during two hepatitis B vaccine studies were compared in RIA and ELISA. In prevaccination sera either HBsAg or anti-HBs were detected by ELISA. Full agreement between the results of RIA and ELISA for anti-HBs was obtained in sera containing more than 10 IU/l anti-HBs. Both tests showed variable results at low titres. Experiments with monoclonal anti-HBs indicated that ELISA is less sensitive for subtype specific antibodies (anti-d, anti-y), which may explain that there were consistent differences between RIA and ELISA in a minority of cases. PMID- 2581989 TI - [Hemoglobin switching in man and the structure of globin genes]. PMID- 2581990 TI - Recovery from aphasia following extracranial-intracranial bypass surgery: case report. AB - The Boston Diagnostic Aphasia Exam and brief measures of memory, stereognosis, and limb praxis were administered to an extracranial-intracranial bypass surgery patient with moderately severe transcortical aphasia preoperatively and postoperatively. Significant improvement in language function was documented 2 days following surgery. Three month followup demonstrated continued improvement across all major areas of language function. These improvements were not felt to be attributable to practice effect, the natural remission of aphasic symptomatology or change in general medical status. Our experience with this patient leads us to speculate that patients with multivessel occlusive disease limiting cerebral oxygen supply to the vascular borderzone area may be more likely to benefit from bypass surgery and an increase in cerebral blood flow than some other subgroups of patients with cerebrovascular disorders. PMID- 2581988 TI - Acute effects of testicular and adrenal cortical blockade on protein synthesis and dihydrotestosterone content of human prostate tissue. AB - To examine the relationship between whole prostatic dihydrotestosterone (DHT) concentrations and epithelial and stromal protein synthesis, patients awaiting surgery for benign prostatic hypertrophy were given medication to reduce circulating and tissue androgen levels for comparison to levels in untreated patients. The medications, either megestrol acetate, a progestational antiandrogen, or megestrol acetate plus dexamethasone, were given for 1 week before surgery. Aliquots of prostate tissue obtained at surgery were assayed for DHT. The remainder of the tissue was separated into stromal and epithelial cells using enzymatic separation; the incorporation of both [3H] proline into stromal protein and [3H]leucine into epithelial cell protein was then measured. Over a wide range of tissue DHT concentrations, DHT correlated significantly with [3H]proline incorporation into stromal protein (r = 0.58). Likewise, epithelial cell incorporation of [3H]leucine into protein correlated significantly with tissue DHT concentrations, with a r value of 0.79. In the case of stromal cells, no additional effects of dexamethasone given with megestrol acetate were found on stromal protein synthesis. Epithelial cell [3H]leucine incorporation into protein was paradoxically enhanced by dexamethasone plus megestrol acetate compared to the latter alone, despite the fact that tissue DHT and circulating adrenal androgens, dehydroepiandrosterone sulfate and delta 4-androstenedione, were not significantly different from values obtained after treatment with megestrol acetate alone. These studies support the conclusion that there is a dominant role of DHT in regulating protein synthesis in both prostatic epithelial and stromal cells. Dexamethasone appears to have a growth-stimulating effect on prostatic epithelial cells. PMID- 2581992 TI - Application of an objective biological assay of human interferons to clinical specimens and a survey of a normal population. AB - A rapid, quantitative, and nonsubjective method of interferon assay is described, which can be readily applied to clinical specimens. Automated data acquisition and data reduction allowed a significant increase in volume per unit of time over existing methodologies. Plasma always yielded higher (usually 2:1) interferon values than did serum obtained simultaneously. Ranges of interferon levels in plasma in normal control populations are reported as well as ranges for clinical virology laboratory technicians and patients with terminal malignancies or collagen vascular diseases. PMID- 2581991 TI - Rapid detection of cytomegalovirus in cell culture by indirect immunoperoxidase staining with monoclonal antibody to an early nuclear antigen. AB - A method for the rapid detection of cytomegalovirus (CMV) in MRC-5 cells 48 h after inoculation with clinical specimens was developed. A commercially available monoclonal antibody to a CMV early nuclear antigen was used in an indirect immunoperoxidase (IPA) staining procedure performed directly on acetone-fixed cell monolayers in standard tubes (16 by 125 mm). Of 190 clinical specimens tested, 30 specimens produced CMV cytopathic effect in tissue culture (TC-CPE) within 14 days after inoculation and, of these 30, 28 were positive for CMV after 48 h by the IPA staining procedure (sensitivity, 93%). Of the remaining 160 clinical specimens negative by TC-CPE within 14 days, 7 were positive by the IPA stain (specificity, 96%). However, three of these seven specimens were positive by TC-CPE upon subculture after the initial 14-day incubation period, and one specimen was overgrown by herpes simplex virus type 2 before CMV cytopathic effect could develop. The mean time to appearance of cytopathic effect for the 30 specimens positive by TC-CPE within 14 days was 6.7 days. These findings indicate that this IPA staining is a useful method for the rapid detection of CMV in cell monolayers inoculated with clinical specimens. PMID- 2581993 TI - Myelin basic protein-specific T cell lines and clones derived from SJL/J mice with experimental allergic encephalomyelitis. AB - Myelin basic protein (BP)-specific T-cell lines and clones have been derived from SJL/J mice which had been sensitized with BP in complete Freund's adjuvant. Cell lines which were initiated and maintained in the presence of BP were specific for this antigen. Cell lines specific for tuberculin-purified protein derivative (PPD) were also established. BP-reactive cell lines maintained for 1 month in culture produced experimental allergic encephalomyelitis (EAE) when transferred to recipient mice. The number of cells required was only slightly less than that necessary for transfer of disease after 3-day culture of sensitized lymph node cells. In contrast, proliferative responses to BP were significantly enhanced after 1 month in culture. Cell lines lost the capacity to transfer EAE after 4 months in culture, but retained a vigorous proliferative response to BP. Similarly, cloned BP-reactive T cells failed to transfer disease, even when recipient mice were treated with IL-2, pertussis vaccine, or low-dose irradiation. Serial FACS analyses demonstrated alterations in cell surface antigen expression, particularly loss of reactivity with anti-Ia antibody, which correlated temporally with loss of ability to transfer disease. Persistence of antigen-induced proliferation by both cloned and uncloned T-cell lines should render these populations suitable for detailed study of the T-cell BP receptor. PMID- 2581994 TI - Experimental allergic neuritis induced in SJL mice by bovine P2. AB - Bovine myelin or bovine myelin-derived P2 protein was injected into 4 inbred mouse strains. SJL mice developed neurological deficit, and histological lesions characteristic of experimental allergic neuritis. BALB/C, CBA and C57.B1/6 mice were relatively resistant to disease induction by this method. PMID- 2581995 TI - Antigenic specificity of acetylcholine receptor in developing muscle. Studies with monoclonal antibodies. AB - Monoclonal antibodies (mcAbs) elicited against the nicotinic acetylcholine receptor (AChR) from Torpedo, were used to follow antigenic changes in AChR during muscle development. Newborn rat muscle and denervated mouse muscle were used as sources of extrajunctional AChR; adult innervated rat and mouse muscle were used as sources of junctional AChR. Most of the mcAbs tested reacted preferably, but not exclusively with extrajunctional AChR (EJR), as compared to junctional AChR (JR). None was found to react with only one of the two forms of AChR. We conclude that the anti-AChR monoclonal antibodies used in this study detect antigenic determinants which are shared by EJR and JR, but which probably undergo structural changes during muscle development. PMID- 2581996 TI - A unique control mechanism in the regulation of insulin secretion. Secretagogue induced somatostatin receptor recruitment. AB - In this study, we have correlated the translocation of somatostatin (SRIF) receptors from the cell interior to the plasma membrane with the ability of SRIF to inhibit insulin release. Islets were perifused with glucose (30, 100, 165, 200, or 300 mg/dl) in the presence of sodium isethionate. Sodium isethionate inhibits insulin release, but not the recruitment of SRIF receptors. Thus, the recruitment of SRIF receptors to the surface membrane continued without the lysis of secretion vesicles. SRIF binding rose from 3.75 +/- 0.16 to 6.46 +/- 0.28 fmol/10 islets as glucose concentration increased. Sodium isethionate was then removed, islets perifused with low glucose (30 mg/dl), and challenged with 400 microM isobutylmethylxanthine (IBMX) with or without SRIF (5 micrograms/ml). In the islets perifused with high glucose concentration, IBMX lysed a greater number of vesicles and caused enhanced release of insulin. The greater the number of secretion vesicles marginated to the plasma membrane by glucose, the greater the response to IBMX. Colchicine (1 mM) prevented secretion vesicle migration and this potentiation effect of higher concentrations of glucose was eliminated. In experiments with IBMX and SRIF, the degree of inhibition of IBMX-induced insulin release by SRIF was proportional to the magnitude of SRIF binding to these islets. SRIF inhibited insulin release by 20 microU/100 islets initially perifused with low glucose (30 mg/dl) and by 875 microU/100 islets perifused with high glucose (300 mg/dl). The maximal effect of SRIF was observed when its binding reached a level of 5.4 fmol/10 islets. We conclude that inhibition of insulin release by SRIF is proportional to the SRIF receptor concentration, and that translocation of SRIF receptors during exocytosis plays an important role in paracrine regulation of insulin secretion by rendering the islets more sensitive to SRIF. PMID- 2581997 TI - Partial restoration of impaired interleukin-2 production and Tac antigen (putative interleukin-2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment in vitro. AB - The in vitro effects of isoprinosine (ISO) on interleukin-2 (IL-2) production, the expression of Tac antigen (IL-2 receptor) on lymphocytes, and the ability of Leu 3(+) cells to absorb interleukin-1 (IL-1) were investigated in 10 patients with acquired immune deficiency syndrome (AIDS). In 9 of the 10 patients, production of IL-2 from mononuclear cells and Leu 3(+) cells was depressed; expression of Tac antigen on mononuclear cells and Leu 2(+) cells was found to be depressed in 9 of 10 patients. The ability of the Leu 3(+) lymphocytes to absorb IL-1 was depressed in all (four of four) patients studied. After ISO treatment, IL-2 production, Tac antigen expression and IL-1 absorption were restored to normal or near normal levels in most of the patients. These results suggest that ISO has an immunostimulating capacity in AIDS patients and that the potential of ISO in immune response restoration in AIDS patients deserves critical consideration. PMID- 2581998 TI - Recognition and characterization of stage-specific oocyst/sporozoite antigens of Toxoplasma gondii by human antisera. AB - Human infection with Toxoplasma gondii is presumed due to the ingestion of either tissue cysts containing bradyzoites or oocyst/sporozoites that are excreted in the feces of infected cats. The incidence of human infection in the general population by either of these routes is unknown. We have previously described unique stage-specific oocyst/sporozoite antigens identified by murine hybridoma monoclonal antibodies. We obtained acute and convalescent antitoxoplasma antisera from patients in an epidemiologically well-documented outbreak of oocyst transmitted infection associated with the ingestion of contaminated water. An enzyme-linked immunosorbent assay comparing equal numbers of tachyzoites (invasive stage) and oocyst/sporozoite (excreted stage) indicated that these antisera recognized antigens from both life forms. Absorption of pooled antisera with purified oocyst/sporozoites reduced both the antioocyst immunoglobulin G (IgG) and immunoglobulin M (IgM) titer but had only minimal effect on the antitachyzoite titer. Absorption of the antisera with tachyzoites reduced the IgG and IgM antioocyst and antitachyzoite titer. A sodium dodecyl sulfate polyacrylamide gel analysis of radioiodinated oocyst/sporozoites shows that the principal stage-specific surface proteins of the oocyst/sporozoite have approximate Mr of 67,000 and 25,000. Periodic acid and silver stain of purified oocyst/sporozoite identified bands of similar molecular weight not present in the tachyzoite preparation. Western blot analysis of purified parasites assayed with human antioocyst antisera identified specific oocyst/sporozoite antigens not present on the tachyzoites. At least two major stage-specific oocyst/sporozoite antigens of approximate Mr of 67,000 and 190,000 were identified by the infected patients' antisera and not by the normal controls. Reaction to these oocyst/sporozoite antigens was seen primarily in the IgM fraction of the acute phase and the IgG fraction of convalescent phase antisera. Neither absorption of the antisera with tachyzoites nor periodate treatment of the oocyst/sporozoites reduced the antibody recognition of these stage-specific antigens. These data suggest that individuals infected by a presumed oocyst-transmitted route develop antibodies against unique stage-specific oocyst/sporozoite antigens. PMID- 2581999 TI - Alpha thalassemia changes erythrocyte heterogeneity in sickle cell disease. AB - Homozygous alpha-thalassemia has the beneficial effect in sickle cell anemia of reducing the hemolytic severity while changing several other hematological parameters. We examined in detail the cellular basis of some of these hematologic alterations. We find that the broad distribution in erythrocyte density and the large proportion of dense cells associated with sickle cell anemia are both reduced with coexisting alpha-thalassemia. Measurements of glycosylated hemoglobin levels as a function of cell density indicate that the accelerated increase in cell density, beyond normal cell aging, in sickle cell anemia is also reduced with alpha-thalassemia. The patients with homozygous alpha-thalassemia and sickle cell disease have slightly lower levels of hemoglobin F than the nonthalassemic sickle cell patients. Examination of hemoglobin F production revealed that the proportion of hemoglobin F containing reticulocytes remained unchanged, as did the proportion of hemoglobin F in cells containing hemoglobin F (F cells). Preferential survival of F cells occurs in sickle cell anemia, with or without alpha-thalassemia, and the slight difference in hemoglobin F levels appear to reflect differences in numbers of circulating F cells. Thus, in sickle cell disease with coexisting alpha-thalassemia, the change in the erythrocyte density profile, possibly due to inhibition of polymerization-related increases in cell density, explains the hematological improvement. PMID- 2582000 TI - Carbon dioxide causes exocytosis of vesicles containing H+ pumps in isolated perfused proximal and collecting tubules. AB - In the turtle bladder it has recently been shown that CO2 stimulates H+ secretion, at least in part, by causing fusion of vesicles enriched in H+ pumps with the luminal plasma membrane. To test for the presence of this mechanism in the kidney we perfused collecting ducts and proximal straight tubules on the stage of an inverted epifluorescence microscope with fluorescein isothiocyanate dextran (70,000 mol wt) in CO2-free medium. After washout we noted punctate fluorescence in endocytic vesicles in some collecting ducts and in all proximal straight tubule cells. More cells took up fluorescent dextran in outer medullary than in cortical collecting ducts. Using the pH dependence of the excitation spectrum of fluorescein we found the pH of the vesicles to be acid (approximately pH 6). Addition of proton ionophores increased vesicular pH by 0.6 +/- 0.1 U, suggesting that the acidity of the vesicles was caused by H+ pumps. CO2 added to the medium (25 mmHg, pH 7.6 at 37 degrees C) reduced fluorescence intensity by 24 +/- 5% in cortical collecting ducts, 27 +/- 5% in medullary collecting ducts, and 25 +/- 5% in proximal straight tubules. Since this effect was prevented by the prior addition of colchicine to the bath, we believe that CO2 caused a decrease in cytoplasmic fluorescence by stimulating exocytotic fusion of the vesicles and thereby secretion of fluorescent dextran. This exocytotic fusion also occurred when tubules that were loaded with fluorescent dextran at a pCO2 of 37 mmHg were exposed isohydrically to a pCO2 of 114 mmHg; the mean decrease was 53 +/- 4%. We conclude that some cells in the collecting ducts and all cells in the proximal straight tubule incorporate fluorescent dextran into the apical cytoplasmic vesicles and acidify them with H+ pumps. CO2 causes fusion of these vesicles with the luminal membrane, but whether CO2 stimulates H+ secretion by increasing the number of functioning H+ pumps remains to be determined. PMID- 2582002 TI - Expression in normal adult, fetal, and neoplastic tissues of a carbohydrate differentiation antigen recognised by antigranulocyte mouse monoclonal antibodies. AB - The distribution in paraffin fixed human tissues of a carbohydrate antigen defined by two monoclonal antibodies raised against human granulocytes has been studied by means of an immunoperoxidase technique. In addition to granulocytes, the antigen has been detected in adult tissues on identifiable cell types of the stomach, kidney, adrenal medulla, and brain and on the mucins of the gastrointestinal tract and other secretions. In fetal tissue, epithelial cells of the alimentary tract, lung, brain, and kidney express the antigen. Adenocarcinoma of the colon, stomach, breast, and lung are stained strongly, as are other types of lung cancer. The monoclonal antibodies give a staining pattern similar but not identical to other monoclonal antibodies raised against granulocytes or neoplastic cell lines which recognise the antigen 3-fucosyl N-acetyllactosamine. The use of antibodies against this oncofetal antigen in the study of differentiation and as tumour markers is discussed. PMID- 2582001 TI - Histamine modulates contraction and cyclic nucleotides in cultured rat mesangial cells. Differential effects mediated by histamine H1 and H2 receptors. AB - Histamine influences the glomerular microcirculation and modulates immune inflammatory responses. In the rat kidney, histamine is synthesized by glomeruli and stimulates cyclic nucleotide production specifically in glomeruli. We investigated the in vitro effect of histamine on cyclic nucleotide accumulation in rat cultured glomerular mesangial and epithelial cells. Histamine stimulated cyclic AMP (cAMP) accumulation in cultured mesangial cells (64.0 +/- 22.1 to 511.4 +/- 86.6 pmol/mg protein, n = 9) but had no effect on cAMP accumulation in epithelial cells. This effect was dose-dependent and time-dependent. Stimulation of cAMP accumulation occurred in the range of 5 X 10(-6) M-10(-4) M histamine with a half maximal stimulatory effect of 2 X 10(-5) M. Initial stimulation was noted by 30 s, and maximum stimulation was observed at 5 min. The H2 antagonist cimetidine (10(-4) M) abolished the stimulatory effect of histamine (10(-4) M), while equimolar concentrations of the H1 antagonist diphenhydramine had no significant effect on cAMP accumulation. Moreover, the specific H2 agonist dimaprit, but not the H1 agonist 2-pyridylethylamine, stimulated cAMP accumulation. Histamine had no effect on cAMP accumulation in epithelial cells or on cyclic guanosine monophosphate accumulation in epithelial or mesangial cells. Since the in vivo infusion of histamine reduces ultrafiltration coefficient and since mesangial cell contraction is thought to be responsible for the reduction in the ultrafiltration coefficient, we examined the effect of histamine on the contractile property of mesangial cells. Histamine (5 X 10(-6)-10(-4) M) contracted mesangial cells, and the H1 antagonist diphenhydramine (10(-4) M) but not the H2 antagonist cimetidine (10(-4) M) prevented histamine (10(-4) M) induced contraction. In addition, the H1 agonist 2-pyridylethylamine, but not the H2 agonist dimaprit, contracted mesangial cells. Histamine and its specific agonists and antagonists induced contraction of isolated glomeruli as assessed by glomerular planar surface area in a manner parallel to their effect on mesangial cells. Cinnarizine (10(-5) M), a Ca++ channel blocker, or Ca++, Mg++-free medium prevented histamine (10(-4) M) induced mesangial cell and glomerular contraction. Thus, histamine enhances cAMP accumulation specifically in mesangial cells via an H2 receptor. In contrast, histamine contracts mesangial cells and glomeruli via an H1 receptor, an effect that is dependent on extracellular Ca++ entry. These findings show that histamine potentially influences intraglomerular hemodynamics via effects on mesangial cell contraction. Moreover, our findings considered with the in vivo observation that histamine reduces kf via and H1 receptor provide further support of the hypothesis that mesangial cell contraction regulates the glomerular capillary surface area available for filtration. Our studies also show that this contractile effect of histamine is dependent on extracellular calcium. The presence of a cAMP system sensitive to histamine may have major implications in the pathogenesis of inflammatory glomerulopathies. Mesangial cells possess characteristics similar to circulating and tissue immune effector cells, including lysosomal enzyme release, oxygen radical production, and release of a number of immunomodulatory factors. Histamine and cAMP have been shown to modulate such characteristics of inflammatory cells. It is therefore conceivable that histamine, via its interaction with H2 receptors and subsequent generation cAMP, may have profound effects on such properties of mesangial cells, suggesting that this autacoid may modulate not only glomerular hemodynamics but also immune, inflammatory responses within the glomerulus. PMID- 2582004 TI - Fine structure of peptidergic and catecholaminergic nerve fibers in the anterior cerebral artery and their interrelationship: an immunoelectron microscopic study. AB - This study shows (1) the ultrastructure of vasoactive intestinal polypeptide (VIP)-, substance P (SP)-, and neuropeptide Y (NPY)-containing nerve fibers in the walls of the cerebral arteries and (2) the relationship between these peptidergic (VIP, SP, and NPY) and catecholaminergic (CA) nerve terminals by immunohistochemistry combined with false transmitter (5-hydroxydopamine) histochemistry under the electron microscope. VIP-, SP-, and NPY-like immunoreactivity (VIPI, SPI, and NPYI) were found diffusely in the axoplasm and around the small clear vesicles in the nerve terminals. In a few cases, SPI was found within the large vesicles. Most of the VIPI terminals were ensheathed by the cytoplasm of the Schwann cells together with CA terminals, identified as those with a number of small granulated vesicles. In some cases, they were directly apposed to the smooth muscle cells at a distance of about 100 nm. SPI terminals were frequently solitary but about 30% were located together with CA and other (neither SPI nor CA) terminals ensheathed by Schwann cells, directly apposed to the smooth muscle cells at a distance of about 100 nm. On the other hand, NPYI terminals were also identified as CA terminals, indicating the coexistence of these two substances. These findings suggest a close interrelationship between peptidergic and CA nerve terminals in the neurogenic control of cerebral blood vessel function. PMID- 2582003 TI - Relation between raised concentrations of fucose, sialic acid, and acute phase proteins in serum from patients with cancer: choosing suitable serum glycoprotein markers. AB - Serum concentrations of fucose, sialic acid, and eight acute phase proteins were measured in single specimens from patients with cancer in order to determine whether the raised concentrations of protein bound sugars commonly found in cancer correlate with increased concentrations of the acute phase proteins. Strong positive correlations were found only with alpha 1-acid glycoprotein, alpha 1-antitrypsin, and haptoglobins. Changes in protein bound sugars and acute phase proteins were also examined in relation to patients' disease states. Serum fucose was raised more often in patients with advanced disease than in those in whom the spread of the tumour was more restricted; increased sialic acid concentrations, however, were found with a similar frequency in both these groups. Combined use of fucose and sialic acid values gave a high degree of marker positivity which could be only slightly improved on by including measurement of acute phase proteins. The combined use of serum fucose and sialic acid concentrations may have value in monitoring patients with cancer: the sialic acid provides an index of the acute phase response and the fucose a measure of the tumour spread. PMID- 2582005 TI - Heterogeneity of ganglia of the guinea pig myenteric plexus: an in vitro study of the origin of terminals within single ganglia using a covalently bound fluorescent retrograde tracer. AB - Experiments were done to test the hypothesis that individual ganglia of the myenteric plexus of the guinea pig small intestine are heterogeneous with respect to the location of the neurons that provide terminals to them. The myenteric plexus, attached to the longitudinal layer of smooth muscle, was maintained in vitro. Individual ganglia were injected with a variety of potential retrograde tracers by pressure microejection from the tip (20-micron diameter) of a glass micropipette. The fluorescent dye 4-acetoamido, 4'-isothiocyanostilbene-2,2' disulphonic acid (SITS) was found to be an effective tracer, labeling neuronal perikarya, evidently by retrograde transport. SITS has previously been shown not to cross plasma membranes, but to be covalently bound to the outer surface of that membrane, and to be taken up by nerve terminals to be retrogradely transported to label neuronal cell bodies. SITS fluorescence was found in about 12% of the neurons within the ganglion into which it was injected and also in approximately ten times more neurons in discretely located distant ganglia. No labeling of neurons was found when SITS was injected into the bath or into the smooth muscle below the myenteric plexus. Damage to neural connectives obstructed the labeling of neurons in ganglia distal to the injection site. Individual SITS injected myenteric ganglia were found to vary greatly in the ratios of intraganglionic SITS-labeled neurons to the total number of neurons within the injected ganglion. The ratios of the number of intraganglionic SITS-labeled neurons to SITS-labeled neurons in distant ganglia projecting to the injected ganglion from elsewhere in the myenteric plexus also varied greatly. More strikingly, individual ganglia differed over a wide range with respect to whether the neurons in distant ganglia that provided them with terminals were situated in the oral, anal, or circumferential direction. Although the majority of projections were found to be from orally located ganglia, individual ganglia were observed that received predominantly or exclusively anal or oral projections. Others received mixtures of terminals from ganglia that were anal, oral, or circumferential. This anatomical heterogeneity in the location of afferent inputs to individual myenteric ganglia is probably reflected in a functional heterogeneity as well and will have to be taken into account in further studies of the physiology of the myenteric plexus. Individual ganglia of the plexus can no longer be taken as anatomically and functionally equivalent to one another. PMID- 2582006 TI - Topographic organization of tufted cell axonal projections in the hamster main olfactory bulb: an intrabulbar associational system. AB - The organization of intrinsic axonal projections of principal neurons in the main olfactory bulb (MOB) was studied in hamsters by using wheat germ agglutinin horseradish peroxidase (WGA-HRP) and fluorescent dyes. Punctate injections of either WGA-HRP or fast blue (FB) that are restricted to small sectors on one side of the MOB produce comparably restricted fields of retrograde labeling on the opposite side. Label is found predominantly in superficially situated (middle and external) tufted cells that lie near and at the border between the external plexiform and glomerular layers. Few of the deeper middle tufted, internal tufted, or mitral cells and no external tufted cells that lie in the superficial two-thirds of the glomerular layer are labeled in regions remote to the injection site. Anterograde transport of WGA-HRP from the injection site labels axons that travel dorsally and ventrally in restricted bands through the internal plexiform layer and then terminate within this layer in the punctate sector on the opposite side that contains retrogradely labeled neurons. Such reciprocal projections between opposing regions of the medial and lateral sides of the MOB are found at all rostrocaudal and dorsoventral levels. When punctate injections of FB into the MOB are paired with restricted injections of a second fluorescent tracer (nuclear yellow or diamidino yellow dihydrochloride) into the appropriate sector of pars externa (pE) of the anterior olfactory nucleus, the punctate region of remote retrogradely labeled principal neurons is embedded within a topographically restricted longitudinal wedge of retrogradely labeled mitral and tufted cells that project extrinsically to or through pE. However, extremely few of these neurons are double-retrogradely labeled. The results reveal the existence of an intrabulbar associational system in which principal neurons engage in point-to point, reciprocal projections between opposing regions of the medial and lateral MOB. Moreover, the results indicate that this associational system largely arises from superficially situated tufted cells distinct from those that support bulbofugal projections into the topographically organized interbulbar commissural system via pE. PMID- 2582007 TI - The nature of pigment in pigmented apocrine hidrocystoma. AB - Apocrine hidrocystomas are often pigmented clinically. The cause of this pigmentation is not known. A case of pigmented apocrine hidrocystoma is presented with evidence of melanin as the underlying mechanism of the pigmentation. Review of an additional 150 cases suggests that this is rare. The Tyndall effect, analogous to that seen in blue dome cysts of fibrocystic disease of the breast may be the likely explanation of the pigmentation seen clinically in most cases of apocrine hidrocystomas. PMID- 2582008 TI - Intimate structural association of amyloid and elastic fibers in systemic and cutaneous amyloidoses. AB - Elastic fibers were found in the amyloid islands of primary systemic amyloidosis, heredo-familial amyloid polyneuropathy, macular amyloidosis and amyloidosis cutis nodularis atrophicans. In macular amyloidosis, the elaunin fibers in amyloid islands were loosely arranged, waved and twisted. In systemic amyloidosis and amyloidosis cutis nodularis atrophicans, amyloid fibers did not deposit in homogeneous electron-lucent material of elastic fiber, but were located close to the elastic fiber where the peripheral microfibrils were present. PMID- 2582009 TI - Bullous congenital ichthyosiform erythroderma masquerading as dystrophic epidermolysis bullosa. AB - A black baby, born at full term of a normal healthy mother, showed multiple erosions and ulcers. No history of skin diseases was known in the family. A skin biopsy taken shortly after birth from an arm lesion showed subepidermal edema and cavity formation. Electron microscopy showed clumping of microfibrils and anchoring fibril-like fibers at the dermo-epidermal junction. In more severely affected areas, absence of anchoring fibrils and collagenolysis were found and the diagnosis of dystrophic epidermolysis bullosa was made. Two weeks later, the lesions healed without leaving scars and a second biopsy from the chest area revealed typical histopathology of epidermolytic hyperkeratosis. PMID- 2582011 TI - The cutaneous pathology of Cowden's disease: new findings. AB - Histological, histochemical and immunohistochemical findings were studied in 40 cutaneous biopsies from 7 patients with Cowden's disease. Most facial biopsies showed a spectrum of trichilemmomas and related follicular malformations, including cylindrical trichilemmomas, lobulate trichilemmomas (14 lesions), and a keratinizing type sharing features with inverted follicular keratosis. One facial growth showed trichilemmomal changes without apparent follicular origin. Studies for common papilloma virus structural antigens were negative, apart from a typical common wart in one patient. Immunohistochemical studies in 6 facial trichilemmomas and acral keratoses, using a panel of anti-keratin antibodies, disclosed only abnormal differentiation with lack of large keratins in the lobulate trichilemmomas. Nine biopsies revealed a distinctive type of fibroma characterized by an organized pattern of interwoven fascicles of collagen bundles with a laminated or tortuous appearance, embedded in abundant mucin. A number of fibromas showed striking hyalinization; these may represent a second microscopic hallmark of Cowden's disease in addition to facial trichilemmomas. PMID- 2582010 TI - Colloid milium: a final degeneration product of actinic elastoid. AB - Serum amyloid P component (SAP) is present not only in all types of cutaneous amyloidosis, but also in the normal dermal elastic fibers as well as abnormal elastic fibers, such as elastotic degeneration of elastic fibers in actinic keratosis. It was previously postulated that the colloid substance in colloid milium is a final degeneration stage of actinic elastosis. In a lesion of colloid milium SAP was intensely positive with an indirect immunofluorescence method using rabbit antiserum to human SAP. Electron microscopy of the colloid lesion revealed components of normal elastic fibers as well as those of actinic elastoid as seen in actinic elastosis. It is concluded that the colloid substance derives, at least in major part, from elastic fibers through actinic degeneration. PMID- 2582012 TI - Adnexal displacement and regression in association with histiocytoma (dermatofibroma). AB - The literature about the changes occurring in histiocytomas mentions only the possibility of induction of primitive pilosebaceous structures and basal cell epithelioma-like lesions by the histiofibrocytic growth. We suggest here that the histopathologic findings are indicative of regressive changes of the pre-existing cutaneous adnexa resulting in the formation of basal cell epithelioma-like structures. PMID- 2582013 TI - Regulation of cyclic 3',5'-adenosine monophosphate phosphodiesterase in Friend erythroleukemia cells. AB - Friend erythroleukemia cells contain only a single form of cAMP phosphodiesterase with high affinity for substrate. It is activated by treatment with various proteases including those present in snake venom. The activity of this enzyme is increased about 2-fold when the cells are either cultivated in the presence of cAMP or in the presence of compounds which are capable of generating cAMP in vivo, such as isoproterenol, epinephrine and prostaglandins. The enzyme produced in the presence of cAMP is modified in such a way that it is no longer susceptible to activation by treatment with proteases. The activation and modification obtained in vivo can be duplicated in cell-free extracts of Friend cells, if they are incubated in the presence of cAMP and ATP. A possibility thus exists that the phosphodiesterase is activated by its substrate by phosphorylation. PMID- 2582015 TI - An evaluation of self-guided teaching methods in a fixed prosthodontics preclinical laboratory. PMID- 2582014 TI - Contribution of extracellular and intracellular calcium to the enhanced effect of an alpha-adrenergic agonist on amylase release from dispersed rat parotid cells. AB - The role of calcium in the potentiation of amylase release by the alpha adrenergic agonist methoxamine (MTX) was examined using dispersed rat parotid acinar cells. The stimulatory effect of MTX (10 microM) on the beta-adrenergic agonist isoproterenol (ISP, 1 microM)-induced amylase release was blocked by the alpha-adrenergic antagonist phentolamine (10 microM). In Ca-free (1 mM EGTA) medium, the increment of amylase release by MTX in normal medium was decreased by about 70%, but MTX still potentiated ISP-induced amylase release. MTX did not affect the cyclic AMP accumulation activated by ISP in either normal or Ca-free medium. MTX enhanced the ISP-stimulated uptake and efflux of 45Ca2+. These results suggest that both extracellular Ca2+ and intracellular stored Ca2+ may play an important role in the potentiation of amylase release from rat parotid acinar cells. PMID- 2582016 TI - Prediction of sudden death and spontaneous ventricular tachycardia in survivors of complicated myocardial infarction: value of the response to programmed stimulation using a maximum of three ventricular extrastimuli. AB - The prognostic significance of ventricular arrhythmias induced by programmed electrical stimulation was evaluated in 50 survivors of acute myocardial infarction complicated by a major new conduction disturbance (38 patients), congestive heart failure (33 patients) or sustained ventricular tachyarrhythmias (22 patients), alone or in combination. Programmed stimulation was performed in patients in stable condition 7 to 36 days (mean 16) after infarction using one to three extrastimuli at four times diastolic threshold at a maximum of two right ventricular sites. Two groups were identified by the response to programmed stimulation: 17 patients with sustained (greater than 15 seconds) or nonsustained (greater than 7 beats but less than or equal to 15 seconds) ventricular tachycardia (group I), and 33 patients with 0 to 7 intraventricular reentrant complexes in response to maximal stimulation efforts (group II). Group I patients had a higher incidence of anterior infarction than that of patients in group II (71 versus 42%), had lower left ventricular ejection fraction (mean 0.35 versus 0.48) and were more often treated with antiarrhythmic drugs (47 versus 18%, p less than 0.05). There were no significant differences between groups in the occurrence of congestive failure, new conduction disorders or sustained ventricular arrhythmias with infarction, or in the proportions treated with a beta-receptor blocking agent, coronary bypass grafting or a permanent pacemaker. Total cardiac mortality was 24% during a mean follow-up period of 23 months and did not differ between groups; however, the response to programmed stimulation identified a group at high risk of late sudden death or spontaneous ventricular tachycardia: 7 (41%) of 17 group I patients compared with 0 of 33 group II patients (p less than 0.001). The induction of sustained or nonsustained ventricular tachycardia identified all patients who died suddenly or had spontaneous tachycardia (sensitivity 100%), but triple extrastimuli were required to induce prognostically significant arrhythmias in five of these seven patients; the specificity of this protocol was only 57%. When the clinical variables of the group were evaluated individually, the response to programmed stimulation had a stronger association with occurrence of late sudden death than did any other factor (Fisher's exact test, p less than 0.001); however, a type II error could not be excluded.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2582017 TI - Comparative study of encainide and disopyramide in chronic ventricular arrhythmias: a double-blind placebo-controlled crossover study. AB - Ten patients suffering from chronic premature ventricular complexes (greater than 60/h) were treated orally in a double-blind crossover study with encainide (50 mg three times a day) and disopyramide (200 mg three times a day), with five 7 day study periods: survey, placebo, encainide or disopyramide, washout placebo and disopyramide or encainide. At the end of each 7 day period, a 12 lead electrocardiogram, a 48 hour ambulatory electrocardiogram and a treadmill exercise test were performed. Blood levels of encainide and its metabolites and of disopyramide were measured at the end of each treatment (steady state). Drug efficacy was assessed by: 1) more than 80% reduction in the number of premature ventricular complexes per 24 hours, and 2) absence of ventricular tachycardia. Encainide was effective in four patients (complete suppression of premature ventricular complexes) and ineffective in five. One patient who showed a 92% reduction in the number of premature ventricular complexes developed sustained ventricular tachycardia after 24 hours of treatment. Disopyramide was effective in three patients (greater than 80% reduction in the number of premature ventricular complexes) and ineffective in seven patients. With encainide, the percent increase in PR, QRS and QT interval duration was, respectively: 32.7 (p less than 0.001), 30.8 (p less than 0.001) and 10.6% (p less than 0.01). With disopyramide this increase was not significant. Despite the variability of drug blood levels, a relation between blood levels and suppression of premature ventricular complexes on the 48 hour ambulatory electrocardiogram was found with encainide, but not with disopyramide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582018 TI - Mechanism of alternating bundle branch aberrancy with atrial bigeminy: electrocardiographic-electrophysiologic correlates. AB - The mechanism of alternating bundle branch aberrancy in response to atrial bigeminy with fixed coupling intervals lacks adequate explanation. In this report, electrophysiologic studies on five patients with fixed coupled atrial bigeminy, identical impulse intervals arriving at the His bundle and alternating bundle branch aberrancy are presented. The mechanism of alternating bundle branch aberrancy in these patients appears to be alternating changes in the refractory periods of the bundle branches resulting from differences in the activation sequence of the distal bundle branches. These findings provide further insight into the mechanism of aberrant conduction. PMID- 2582019 TI - Hepatotoxicity in albino rats exposed to n-octane and n-nonane. AB - Effects of n-octane and n-nonane (1 ml per kg body weight daily) on hepatic and serum enzymes, which reflect abnormal liver function and concentration of lipid and nucleic acid (serum and liver), were studied after 2 and 7 days intraperitoneal administration to albino rats. Decreased activities of serum acetylcholine esterase and carboxyl esterase were observed, together with an increase in FDP aldolase activity. Significant decrease in the concentration of albumin, total protein, and total and esterified cholesterol in serum have been noted after n-octane and n-nonane administration for 7 days. Also, free cholesterol content of liver was elevated significantly after solvents exposure. PMID- 2582021 TI - Affinity chromatography of mustard beta-amylase on starch columns. AB - An affinity chromatography method for purification of beta-amylase from cotyledons of white mustard seedlings (Sinapis alba L.) is described. beta Amylase is bound to starch column, while other contaminating proteins are eluted with the binding buffer. The bound beta-amylase is eluted by including dextrin (1%, w/v) in binding buffer. This method yielded a homogeneous preparation of beta-amylase enzyme, which migrated as a single polypeptide band in SDS gel electrophoresis. PMID- 2582020 TI - Effects of bleomycin on 14C-proline uptake, its incorporation into proteins and hydroxylation in collagenous proteins of hamster lung slices. AB - The uptake of 14C-proline by lung slices and its incorporation into trichloroacetic-acid (TCA)-insoluble proteins and hydroxylation in collagenous proteins were studied. They were found to be linearly increased with the incubation time for as long as 8 h. The effects of different concentrations of bleomycin on these parameters were subsequently investigated. Bleomycin at 10(-3) M significantly reduced the uptake of 14C-proline to 75% of the control value. The incorporation of 14C-proline into TCA-insoluble proteins was reduced to 84%, 78% and 75% of the control at 2.5 X 10(-4) M, 5 X 10(-4) M and 10(-3) M concentrations of bleomycin, respectively. Bleomycin failed to alter the proline pool size of the lung slices at any of these concentrations. In addition, bleomycin also inhibited the hydroxylation of 14C-proline into collagen to 72% and 69% of the control at 5 X 10(-4) M and 10(-3) M, respectively. These findings show that bleomycin-induced increases in collagen synthesis in vivo is probably secondary to inflammatory reactions of the lung and bleomycin per se has little effect on increased collagen synthesis responsible for lung fibrosis. PMID- 2582022 TI - Immobilization of native and denatured DNA on Sephadex G200. AB - An efficient method for the immobilization of DNA on Sephadex G200 in the presence of water soluble carbodiimide is described and investigated in this paper. An increase in the extent of binding was observed when the incubation temperature of the DNA-Sephadex mixture was changed. It was found that native DNA immobilized to Sephadex with higher efficiency than denatured DNA. However, the stability of native DNA-Sephadex complex was about the same as that of denatured DNA-Sephadex. The size of DNA released by DNA-Sephadex after incubation of a suspension of the complex was the same as that of the DNA used for immobilization. The binding mechanism of DNA to Sephadex is discussed. PMID- 2582023 TI - The role of substance P in arterial chemoreflex control of ventilation. AB - The postulate that Substance P (SP) plays a neurotransmitter-like role in the arterial chemo- and thermoreflex control of ventilation was examined in conscious rabbits. The investigation was based on CNS neurotransmitter criteria and involved morphological studies using a monoclonal SP antibody, and functional experiments which compared within-animal responses to severe arterial hypoxia (PaO2 less than 35 mm Hg) and to intracisternal SP infusions. Experiments were performed in normal rabbits, and in rabbits pretreated at birth with capsaicin. The data support a neurotransmitter-like role for SP in the arterial chemo- and the thermoreflex control of ventilation, and there appear to be SP-dependent collateral chemoreflex pathways which block thermoregulatory panting through an inhibitory interneuron system. PMID- 2582024 TI - Origin of small primary afferent substance P-immunoreactive nerve fibers in the guinea-pig heart. AB - Primary afferent and substance P (SP)-immunoreactive nerve fibers of the guinea pig and rat heart were investigated by physiological and immunohistochemical methods. Immunohistochemistry revealed abundant SP-positive fibers in the guinea pig atria, with fewer in the ventricles. Only an occasional fiber was seen in the rat atrium or ventricle. Sectioning the vagus nerve did not noticeably influence the supply of SP-immunoreactive nerve fibers in the guinea pig heart. When the atria or ventricles were stimulated, afferent nerve fiber activity was recorded from the second and third thoracic dorsal roots. In guinea pig atria 3 types of fibers were identified on the basis of conduction velocities: A delta 1, A delta 2 and C fibers. Only A delta fibers were identified in the ventricle. By vagal recordings, A delta fibers were demonstrated but a C fiber response could not be shown in this nerve. SP-immunoreactivity in primary afferent fibers was depleted by the neurotoxin capsaicin. Capsaicin treatment also caused a reduction in the conduction velocity of small diameter myelinated A delta 2 (by 29%) and unmyelinated C fibers (by 46%). In the rat heart, evidence for A delta 2 or C fibers was not found. These results indicate that primary afferent and SP immunoreactive fibers are numerous in guinea pig heart, but few in the rat. It is concluded that most of these fibers have their cell bodies of origin in the dorsal root ganglia. PMID- 2582025 TI - Spinal cord substance P mediates bicuculline-induced activation of cardiovascular responses from the ventral medulla. AB - Substance P (SP) and serotonin are contained in ventral medullary projections to the intermediolateral cell column (IML) of the spinal cord, and both neurotransmitters excite sympathetic preganglionic neurons upon injection into the IML. Since gamma-aminobutyric acid (GABA) in the ventral medulla inhibits, and GABA-receptor antagonists excite sympathetic outflow to the cardiovascular system, experiments were done to determine if SP and serotonin in the spinal cord were responsible for mediating these GABAergic effects. Anesthetized rats were either given intrathecal injections of SP antagonists acutely, or pretreated with intrathecal injections of the serotonin neurotoxin, 5,7-dihydroxytryptamine. The effects of these drugs on mean arterial pressure (MAP) and heart rate (HR), as well as their ability to block the responses to topical application of GABA or the GABA antagonist, bicuculline, at the ventral medulla were assessed. Three SP antagonists (50 micrograms) decreased MAP to 2/3 baseline values, but did not change HR. They also blocked the characteristic increases in MAP and HR elicited by application of bicuculline to the ventral medulla. A lower dose (5 micrograms) of a SP antagonist also decreased MAP and blocked the bicuculline-induced increases in MAP and HR, an effect which was reversed in 1-2 h. Neonatal capsaicin treatment reduced the SP content in the dorsal horns of the thoracic spinal cord, but did not affect the cardiovascular responses to intrathecal injection of SP antagonist nor the blockade of bicuculline-induced responses. Intrathecal injection of 5,7-dihydroxytryptamine two weeks prior to the experiments resulted in 56% depletion of serotonin in the thoracic spinal cord, but did not change either basal MAP and HR, nor the responses to bicuculline and GABA applied to the ventral surface of the medulla. These data provide evidence for a role of spinal cord SP in cardiovascular regulation. PMID- 2582027 TI - Preembedding colloidal gold immunostaining of hypothalamic neurons: light and electron microscopic localization of beta-endorphin-immunoreactive perikarya. AB - A preembedding immunogold staining (IGS) procedure was developed to identify beta endorphin/adrenocorticotropic hormone immunoreactive neurons at the light and electron microscopic levels. Colchicine-treated rats were perfused with Nakane's periodate-lysine-paraformaldehyde fixative. Vibratome sections were incubated in primary antisera followed by goat anti-rabbit immunoglobulin G coupled to 16 nm colloidal gold, and, in some cases, rabbit immunoglobulin G coupled to gold. The appearance to pink to light red perikarya, corresponding to colloidal gold deposition at antigenic sites, was monitored under the light microscope. Positive cell bodies in the arcuate region sometimes extended lateral to the nucleus. Only proximal portions of neuronal processes were stained. At the ultrastructural level, colloidal gold labeled the periphery of 90-110 nm dense neurosecretory granules in the perikaryal cytoplasm and a few proximal axons. Clusters of gold particles, appearing free in the neuroplasm, actually labeled secretory granules in adjacent thin sections. Granules associated with the Golgi apparatus were not stained. Colloidal gold labeling of mature beta-endorphin granules, but not progranules, in rat hypothalamic neurons was confirmed using the peroxidase antiperoxidase technique. The results correlate well with data on the intracellular processing of pro-opiomelanocortin in pituitary cells and prepropressophysin in the paraventricular nucleus. These data demonstrate the first application of the preembedding colloidal gold staining method for the identification of intracellular antigens within the central nervous system. The IGS method provides a definitive marker for single or double labeling of nervous tissue at both the light and electron microscopic levels. PMID- 2582026 TI - [Current aspects of the Vogt-Koyanagi-Harada syndrome. Apropos of 9 cases]. AB - We have studied 9 cases of the Vogt Koyanagi Harada (VKH) syndrome as defined by the criteria of the American Uveitis Society; all these cases presented evidence of past or present exudative retinal detachment (RD). In 2 cases the RD was shallow and limited to the posterior pole, in 3 cases encephalo-meningeal symptoms were absent, in 2 cases skin and hair symptoms were absent. In all, 5 cases in this series presented as an incomplete, dissociated form of the disease. However the clinical cause of the disease in these "formes frustes" was not simpler or quieter than in the complete forms; incomplete response or drug dependence were encountered with steroid therapy, and immunosuppressive drugs were used in 3 cases. It is to be noted that in one case an extensive RD involving the posterior pole occurred bilaterally: this RD did not respond to maximal steroid and immunosuppressive therapy and reattachment was obtained only after vitrectomy. In another case bilateral optic disc neovascularization was observed in association with severe papillitis despite heavy steroid therapy. A cure was obtained with immunosuppressive drugs. PMID- 2582028 TI - Adenosine deaminase complexing proteins are localized in exocrine glands of the rabbit. AB - Adenosine deaminase complexing proteins have been localized in four exocrine glands of the rabbit by immunoperoxidase staining employing affinity-purified goat anti-rabbit complexing protein immunoglobulin as the primary antibody. In pancreatic acinar cells and in serous cells of Brunner glands (duodenal glands), staining was concentrated in granular appearing deposits between the nucleus and cell apex. Bile canaliculi, components of the exocrine liver, were also positive for complexing protein. In submaxillary glands, staining was localized in serous demilunes and striated ducts. In each instance staining was blocked by preincubating the primary antibody with complexing protein purified from rabbit kidney. PMID- 2582029 TI - Target specificity and cell surface structures involved in the human cytolytic T lymphocyte response to endothelial cells. AB - Two long-term cytolytic T lymphocyte (CTL) lines derived from the peripheral blood lymphocytes (PBL) of a single donor were analyzed for target specificity and involvement of cell surface molecules in CTL-target interactions. One line, AH2, was generated after stimulation with B lymphoblastoid cells. Cytolysis by these cells was restricted to targets expressing the appropriate HLA-A2 specificity and was blocked by mAb recognizing CD2, CD3, CD8, LFA-1, and LFA-3. The second line, AE1, was generated after stimulation with cultured endothelial cells derived from human newborn preputial microvessels. These CTL lysed all human target cells tested, except autologous cells and the Class I negative cell line Daudi. In addition, mAb specific for CD2, CD3, and CD8 did not affect cytolysis. Anti-LFA-1 and -LFA-3 mAb blocked cytolysis of B lymphoblastoid targets but not endothelial targets. These results indicate that some CTL utilize as yet uncharacterized cell surface structures for CTL-target interactions. PMID- 2582030 TI - Identification and purification of NK cells with lysosomotropic vital stains: correlation of lysosome content with NK activity. AB - The lysosome content of lymphocytes has been analyzed with lysosomotropic vital stains and the fluorescence-activated cell sorter (FACS). Large granular lymphocytes (LGL), which account for virtually all natural killing activity in peripheral blood, are quantitatively different from small lymphocytes (SL) in this respect. LGL obtained by Percoll gradient density centrifugation accumulate more of the lysosomotropic vital dyes than SL do, staining with either neutral red or mepacrine (quinacrine). Furthermore among the LGL-rich, low density lymphocyte population highly, granulated cells can be separated from less granulated ones by mepacrine staining and FACS. Thus, separated highly granulated LGL express very high natural killing, whereas the less granulated low density large lymphocytes do not kill. PMID- 2582032 TI - A myelin basic protein-specific T lymphocyte line that mediates experimental autoimmune encephalomyelitis. AB - A T lymphocyte line, BP-1, expressing the T helper phenotype was selected from Lewis rats immunized with guinea pig myelin basic protein (GP-BP) in complete Freund's adjuvant (CFA). The BP-1 line responded specifically to GP-BP but not to PPD after the first round of selection, and responded to rat but not human or bovine BP. When injected i.p. into histocompatible Lewis or F1 (Lewis X P2) recipients, the BP-1 line induced both clinical signs of experimental autoimmune encephalomyelitis (EAE) and delayed type hypersensitivity (DTH) reactions in ears challenged intradermally with GP-BP but not PPD. The severity of clinical signs and the degree of ear swelling were dependent on the dose of BP-1 cells injected. Both activities were detectable with as few as 0.1 X 10(6) BP-1 line cells and required prior activation of the line cells with GP-BP presented by accessory cells. Lewis rats that had recovered from EAE induced by injection of GP-BP in CFA were more susceptible than naive rats to BP-1 line-mediated disease, requiring as few as 0.03 X 10(6) line cells. Clinical EAE and DTH could be serially transferred into F1 (Lewis X P2) recipients with BP-1 cells and back to nonirradiated Lewis parents with activated splenocytes, suggesting that BP-1 cells persist in recipient rats. These results demonstrate the potent biologic activities of an autoreactive BP-specific T lymphocyte line. This line possesses properties similar to BP lines described previously as well as to culture conditioned splenic T effector cells; thus, the data presented here bridge the gap between these two approaches for studying T effector lymphocyte functions. PMID- 2582031 TI - The induction and suppression of in vitro IgG anti-tetanus toxoid antibody synthesis by human lymphocytes stimulated with tetanus toxoid in the absence of in vivo booster immunizations. AB - This report presents a new approach that by-passes booster immunizations with tetanus toxoid (TT) before in vitro studies of antibody (Ab) production. The methodology for optimal TT-induced synthesis of specific IgG anti-tetanus toxoid Ab (IgG anti-TT) by peripheral blood mononuclear cells (PBMC) from randomly selected TT immune individuals without recent booster immunizations is described. PBMC from most normal immune subjects could be repeatedly induced to produce in vitro IgG anti-TT; PBMC from subjects with high TT titers are not required for this new approach. This approach uses high cell concentrations in multiple replicate microcultures and TT washout to obtain optimal IgG anti-TT synthesis. Washed cultures produced more Ab than nonwashed cultures (p less than or equal to 0.005). The readdition of TT (2.5 to 250 ng/ml) to the culture media after washout of TT on day 4 suppressed specific Ab formation, whereas diphtheria toxoid added at comparable doses did not inhibit specific Ab formation. Suppression of antibody synthesis mediated by T cells could be induced by TT per se, and was not due to binding of synthesized Ab to TT in the latter 8 days of culture. In addition, suppression could not be induced in the first 4 days of culture by IgG anti-TT, IgG, or IgM. This approach permits the analysis of antigen-specific regulatory circuits in the steady and activated immune states, and the evaluation of in vivo and in vitro effects of biologic response modifiers on specific Ab production. PMID- 2582033 TI - Specificity of T lymphocyte lines for peptides of myelin basic protein. AB - T lymphocyte lines specific for myelin basic protein (BP) can mediate experimental autoimmune encephalomyelitis (EAE), or can protect against the active induction of the disease. To investigate the antigenic fine specificity of guinea pig (GP) BP-specific T cell lines raised from different rat strains, and to determine whether functionally different T lymphocyte lines and clones recognized the same or different regions of the BP molecule, the proliferation responses of line cells were assessed after stimulation with purified peptides of GP-BP. Lewis rat T cell lines and clones selected for responses to whole GP-BP responded selectively to the 68-88 amino acid sequence of GP-BP, but not to the 1 37, 43-67, or 89-169 sequences. The region of GP-BP recognized by Lewis T cells was additionally defined to include the 75-80 amino acid sequence, because a T cell clone responded equally to GP and rat BP which differed by only one amino acid at position 79, but did not respond to human or bovine BP, which had a Gly His insertion in this region. T lymphocyte lines derived from the F344 and PVG (Weizmann) rat strains shared the same selective response to peptide 68-88, but lines from BN rats responded to an epitope(s) outside of the 68-88 sequence. The functional capacity of the various T cell lines to mediate experimental autoimmune encephalomyelitis (EAE) or to induce resistance against EAE was independent of their specificity for the different GP-BP peptides; lines specific for epitope(s) within or excluded from the 68-88 sequence could be encephalitogenic depending on their strain of origin, and various lines specific for the 68-88 peptide could induce both disease and protection, disease only, or neither activity. PMID- 2582034 TI - Protein-antigen specific Ia-restricted cytolytic T cells: analysis of frequency, target cell susceptibility, and mechanism of cytolysis. AB - We previously showed that cloned, antigen-specific, Ia-restricted L3T4a+ T cell lines can be cytolytic for antigen-pulsed B cell lymphoma targets. Such cells can also, under different experimental conditions, activate B cells to proliferate and secrete immunoglobulin. In the present experiments, we show that this functional phenotype is a common one among a panel of cloned T cell lines. In keeping with this finding, freshly isolated, antigen-activated lymph node T cells show similar functional properties. Such cytolytic L3T4a+ T cells differ from classical H-2K/D-restricted cytolytic T cells in two distinct ways. First, Ia restricted cytolytic T cells can kill bystander targets, whereas H-2K/D-specific cytolytic T cells do not. Second, in testing a panel of target cells by using lectin-mediated cytolysis, Ia-restricted cytolytic clones reveal large differences in target cell susceptibility, whereas all targets are similarly susceptible to H-2K/D-specific killer cells. Finally, evidence is presented that both direct and bystander killing effected by L3T4a+ T cells are mediated by the same soluble factors, in that there is a strong positive correlation of these two activities for individual cloned lines. The relevant mediators appear to be lymphotoxin and IFN-gamma, although the latter molecule by itself is not cytolytic on our target lines. PMID- 2582035 TI - Murine interstitial nephritis. IV. Long-term cultured L3T4+ T cell lines transfer delayed expression of disease as I-A-restricted inducers of the effector T cell repertoire. AB - In the present study we observed that long-term cultures of tubular antigen reactive L3T4+ T cells from immune SJL mice are able to adoptively transfer interstitial nephritis by 12 wk after i.v. injection. Lesions that develop under these conditions generally occur in the absence of anti-tubular basement membrane antibody formation. These cultured T cell lines are I-A restricted, require L3T4 associative interactions, and are tubular antigen specific, but do not share the phenotype, function, or H-2-restriction characteristics of Lyt-2+ nephritogenic effector T lymphocytes. Rather, our L3T4+ T cell lines, and phenotypically similar lymphocytes harvested from renal infiltrates, are inducers of this Lyt-2+ effector T cell repertoire. Such effector T cells, typically found in immune lymph nodes 4 to 7 days after immunization, can be induced in vitro within 5 days and will acutely transfer disease within another 5 days when placed under the kidney capsule. These findings collectively indicate that the time course for optimal effector cell differentiation and potential expression is relatively short. The immunologic inertia we previously observed between immunization or i.v. adoptive transfer and the development of cellular lesions, therefore, seems to reside in other systemic or interactional events beyond the timely formation of effector T cells. PMID- 2582036 TI - T3 monoclonal antibody activation of nonspecific cytolysis: a mechanism of CTL inhibition. AB - The T3 antigen is expressed on all cytotoxic T lymphocytes (CTL). Monoclonal antibodies (MAb) to the T3 antigen previously have been shown to inhibit CTL mediated killing of cells expressing the relevant target antigens. The mechanism of T3 MAb inhibition, however, remains undefined. In this report, we describe a novel effect of the T3 MAb: the stimulation of allospecific CTL clones to kill target cells that do not express the relevant HLA antigens. The stimulation of nonspecific killing was seen only with MAb to the T3 antigen; MAb to other function-associated antigens (e.g., LFA-1, LFA-2, LFA-3, T4, T8, HLA-A,B,C, and DR) had no effect. T3 MAb stimulated nonspecific killing by CTL clones expressing both the T4+ and T8+ phenotype and by CTL clones specific for both class I and class II HLA alloantigens. Target cell susceptibility to T3 MAb stimulated killing was variable. CTL clones lysed some target cell lines very efficiently (e.g., K562, Daudi, and M124.1) but lysed other cell lines much less efficiently (e.g., 23.1, Mann, and L cells). In CTL-mediated cytotoxicity assays with target cells expressing the relevant HLA antigens, T3 MAb demonstrated the expected inhibition of cytolysis. Thus, the ability of T3 MAb to stimulate and inhibit CTL mediated cytolysis suggests that both effects may be the result of a common mechanism of activation. PMID- 2582037 TI - Modulation of macrophage-mediated tumoricidal activity by neuropeptides and neurohormones. AB - Recent evidence has suggested that stress may suppress the immune system and increase the frequency and severity of viral and neoplastic disease. The mechanisms for stress-induced modulation of immune function are unclear, but several neuropeptides are thought to be involved. Because macrophages play an important role in the host defense against infection and neoplasia, several stress-related neuropeptides were screened in efforts to determine whether these substances affect macrophage-mediated tumoricidal activity. Adrenocorticotropin and noradrenaline each completely blocked the capacity of mouse recombinant interferon-gamma (INF-gamma) to activate murine peritoneal macrophages to a tumoricidal state as measured by the lysis of 125I-UdR-labeled melanoma target cells. Vasoactive intestinal peptide significantly potentiated the suppressive effects of noradrenaline. In contrast, neurotensin markedly enhanced the cytolytic capability of peritoneal macrophages activated with INF-gamma. Several other neuropeptides, including substance P, alpha-endorphin, beta-endorphin, Leu enkephalin, and Met-enkephalin, had no effect on macrophage activation. These findings demonstrate that selected stress-related neuropeptides and neurohormones significantly modulate the capacity of macrophages to attain a tumoricidal state and suggest that alteration of macrophage function by neuropeptides may be a prominent feature of stress-induced enhancement of neoplastic disease. PMID- 2582038 TI - Monoclonal antibodies specific for single chain or two chain GAT-specific suppressor factors: production and analysis of in vitro modulating properties. AB - Fusion of spleen cells from rats hyperimmunized with T cell hybridoma derived GAT specific TsF1 or TsF2 suppressor T cell factors has resulted in the generation of hybridomas secreting monoclonal antibodies reactive with the appropriate GAT-TsF used for immunization, and in several cases, reactive with other GAT-TsF1 and TsF2. The monoclonal anti-TsF1 antibodies are capable of modulating in vitro GAT specific PFC response in a GAT-specific manner; some suppress responses to GAT directly, whereas others reverse GAT-TsF1-mediated suppression of responses. The monoclonal anti-TsF2 antibodies all reverse suppression but are reactive with combinatorial determinants, I-J+ chains or antigen-binding chains of the GAT TsF2. The data are discussed in terms of the nature of the determinants recognized by these antibodies as well as the potential uses of these reagents for studying the suppressor T cell pathway and potential relationships between Ts1, Ts2, and T helper cells. PMID- 2582039 TI - Specificity of the T cell receptor: two different determinants are generated by the same peptide and the I-Ak molecule. AB - The determinants recognized by two I-Ak-restricted hen egg-white lysozyme specific T cell hybridomas were differentiated with a series of truncated or substituted peptides. The 10mer 52-61 was the smallest peptide that was immunogenic for both T cells. This peptide differed by a single residue, Leu56, from the corresponding autologous lysozyme peptide, which was nonimmunogenic. The addition of amino acids to the amino terminus of 52-61 increased the immunogenicity of the peptides for 3A9 T cells and decreased the immunogenicity for 2A11 T cells. By deleting or diiodinating Tyr53, the resulting peptides were rendered totally nonimmunogenic. In contrast, the 3-NO2-Tyr derivative was fully immunogenic for the 3A9 cells but completely nonimmunogenic for the 2A11 cells. Thus, two different, but very similar, determinants were generated by the same HEL peptide and the I-Ak molecule. PMID- 2582040 TI - Novel antigenic determinants of the T200 glycoprotein expressed preferentially by activated cytotoxic T lymphocytes. AB - This report describes the production and characterization of MAb specific for neoantigenic determinants, called CT antigens, present on the T200 glycoprotein of CTL. The CT determinants are expressed at high levels only on activated CTL. Although differences had previously been noted in the cell surface protein profile of distinct T cell subsets, this is the first description of a lineage specific activation antigen. Furthermore, these determinants appear to have functional significance, because the CT-specific MAb block cytolytic function. Immune precipitation experiments indicated that the appearance of the CT antigens correlated with m.w. changes and the appearance of additional T200 protein species that were CTL specific. MLC cells cultured in the presence of IL 2 containing supernatants undergo a gradual shift from relatively low CT antigen expression to very high CT expression. This shift is accompanied by modifications of T200 eventually leading to a T200 protein profile identical to that of CTL clones. However, MLC cells propagated without the addition of IL 2-containing supernatants do not undergo a shift in CT antigen expression. Thus, the extent to which modifications occur in the T200 molecule is regulated by soluble factors. Competitive binding assays with two CT-specific MAb indicated that at least two distinct but overlapping neo-epitopes appear as the result of the T200 alterations. In sum, we have discovered the presence of CTL-lineage-specific activation antigens whose expression is regulated by lymphokines and is linked to cytolytic function. MAb specific for determinants such as these could be invaluable tools in the enumeration and depletion of specific T cell subsets in in vivo situations. PMID- 2582041 TI - Clonal T lymphocyte recognition of the fine structure of the HLA-A2 molecule. AB - A human alloimmune cytotoxic T lymphocyte (CTL) clone (4E4) was generated against the HLA-A2 molecule. Lysis of 51Cr-labeled HLA-A2 target cells was blocked by monoclonal antibodies (mAb), including mAb PA2.1 (anti-HLA-A2), mAb BB7.2 (anti HLA-A2), mAb 4B (anti-HLA-A2-plus-A28), mAb MA2.1 (anti-HLA-A2-plus-B17), and mAb W6/32 (anti-HLA-A,B,C), which are directed against different serologic epitopes on the HLA-A2 molecule. However, HLA-A2 mutant lines lacking the serologic epitope recognized by mAb BB7.2 (anti-HLA-A2) were efficiently lysed by CTL 4E4. Thus, although mAb may block cytolysis, the HLA-A2 epitope recognized the 4E4 CTL clone is distinct from the HLA-A2-specific epitope recognized by serologic reagents. Moreover, analysis of HLA-A2 population variants revealed that only the predominant HLA-A2.1 subtype molecule was recognized by CTL 4E4. No cross reactivity on other, biochemically related HLA-A2 population subtypes was observed, including HLA-A2.2 cells (Hill, CVE, ZYL, M7), HLA-A2.3 cells (TENJ, DK1), or HLA-A2.4 cells (CLA, KNE). This CTL clone appears to recognize a single epitope and, like monoclonal antibody counterparts, can be used to discriminate among immunogenic cellular and serologic epitopes on closely related HLA-A2 molecules. On the basis of the known sequence changes in mutant and subtype HLA A2 molecules, it appears that the sequence spanning residues 147 to 157 may be critical for cellular recognition of this Class I MHC molecule. PMID- 2582042 TI - A murine monoclonal antibody recognizes the 13,000 molecular weight polypeptide of the Sm small nuclear ribonucleoprotein complex. AB - Antibodies to the Sm antigen are closely associated with the rheumatic disease systemic lupus erythematosus (SLE). The Sm antigen exists in the cell as part of a ribonucleoprotein complex containing at least 10 polypeptides and five small nuclear RNA. The major immunoreactive Sm species are three polypeptides of m.w. 27,000, 26,000, and 13,000. By using an MRL/1 mouse, a strain which spontaneously produces a disease with many of the characteristics of human SLE, we have produced an anti-Sm hybridoma specific for the 13,000 m.w. Sm polypeptide. This monoclonal antibody is sufficient to allow for the rapid bulk isolation of the entire class of Sm snRNP, and can be used sequentially with an anti-(U1)RNP monoclonal antibody to subfractionate the Sm snRNP particles. PMID- 2582043 TI - Successful generation of cytotoxic T lymphocytes specific for self immunoglobulin determinants on B lymphocytes. AB - Cytotoxic T lymphocytes (CTL) specific for self immunoglobulin (Ig) determinants on B lymphocytes were successfully generated. These CTL were induced with stimulator B hybridoma cells bearing self Ig determinants in responders compatible with the stimulators in H-2 antigens but disparate in minor H antigens. Their specificities were directed toward the idiotype and probably the allotype structures of Ig receptors on stimulator B cells. However, no CTL specific for Ig structures other than the idiotype and the allotype were detected. These data indicate the presence of specific precursor CTL for self B cell clones and suggest the possible development and function of these CTL in certain situations. PMID- 2582044 TI - Structural analysis of the epitope recognized by a monoclonal antibody directed against tricyclic antidepressants. AB - After somatic cell fusion between splenocytes of immunized BALB/c mice and NS-1 myeloma cells, a clone was obtained that secreted an anti-nortriptyline antibody of the IgG1 kappa isotype. The association constant of this antibody for pharmacologically active tricyclic antidepressant drugs ranged from 0.6 X 10(7) to 3 X 10(7) M-1. From thermodynamic and binding studies as well as tridimensional structures of tested compounds, the epitope recognized by the monoclonal antibody appeared to include both a hydrophobic tricycle in which the two phenyl rings form an angle of 120 to 130 degrees, and a side chain in which the amino group is separated from the two lateral rings of the tricyclic structure by a distance of approximately 5.9 A and 7.5 A, respectively. This conformation seems to be the one interacting with muscarinic acetylcholine brain receptors. PMID- 2582045 TI - Isolation and characterization of human intestinal mucosal mast cells. AB - Study of the role of mast cells in the human gastrointestinal tract has suffered from the inability to examine these cells in vitro. In addition, work in rodent systems suggests that there are substantial differences between intestinal mast cells and those from other tissues, making extrapolation of data from other sources difficult. We report a method for producing mast cell-containing single cell suspensions from human intestinal tissue by mechanical and enzymatic dispersion. This method yields 4.5 X 10(5) mast cells per gram of tissue in purity of 3.1 +/- 2.1%. These mast cells were functionally intact as assessed by survival in short-term culture, low spontaneous release, and appropriate IgE mediated histamine release. They were morphologically intact on electron microscopy and conformed to published descriptions of human lung mast cells. The intestinal mucosal mast cells were also indistinguishable from human lung mast cells in histamine content, goat anti-human IgE dose-response curves, kinetics of histamine release, unresponsiveness to f-met peptide, and production of arachidonic acid metabolites, prostaglandin D2, and leukotriene C4. This procedure produces human intestinal mast cell suspensions in sufficient numbers to make pharmacologic characterization and further purification of this cell feasible. PMID- 2582046 TI - Biochemical analysis of desensitization of mouse mast cells. AB - Biochemical mechanisms of desensitization were explored by using peritoneal mouse mast cells saturated with monoclonal mouse IgE anti-DNP antibody. It was found that a 1-min incubation of the sensitized cells with 0.01 micrograms/ml DNP-HSA in the absence of Ca2+ was sufficient to desensitize the cells completely. The treated cells failed to release a detectable amount of histamine upon incubation with an optimal concentration (0.1 to 1.0 micrograms/ml) of DNP-HSA and Ca2+. Determination of the number of antigen molecules bound to mast cells revealed that only a small (less than 10%) fraction of cell-bound IgE antibody molecules reacted with desensitizing antigen, and that desensitized cells and untreated (sensitized) cells could bind comparable amounts of antigen upon incubation with rechallenging antigen. However, the binding of antigen molecules to desensitized cells failed to induce any of the early biochemical events, i.e., phospholipid methylation, cAMP rise, and 45Ca uptake, as well as histamine release. It was also found that intracellular cAMP levels in desensitized cells were comparable to those in sensitized cells. Desensitization by a suboptimal concentration of DNP-HSA was prevented by inhibitors of methyltransferases, such as 3-deaza adenosine plus L-homocysteine thiolactone. Sensitized cells pretreated with 0.01 micrograms/ml DNP-HSA in the absence of Ca2+ and in the presence of the methyltransferase inhibitors responded to an optimal concentration of antigen for histamine release when they were rechallenged in the presence of Ca2+. Inhibition of desensitization by methyltransferase inhibitors was reversed by the addition of S-adenosyl-L-methionine to the system. The results indicated that the activation of methyltransferases, induced by receptor bridging, is involved in the process of desensitization. Desensitization was inhibited by reversible inhibitors of serine proteases, such as p-aminobenzamidine, indole, and synthesized substrates of rat mast cell proteases. It was also found that diisopropylfluorophosphate (DFP), an irreversible inhibitor of serine proteases, completely blocked desensitization at the concentration of 10 to 40 nM. This concentration of DFP did not affect the antigen-induced histamine release, whereas 100- to 1000-fold higher concentrations of DFP did inhibit histamine release. The results suggest that serine proteases are involved in both the induction of histamine release and desensitization, and that the protease involved in desensitization is distinct from that involved in triggering histamine release. PMID- 2582048 TI - Effects of sodium on chemotactic peptide binding to polymorphonuclear leukocytes. AB - The affinity of binding of the chemotactic peptide N formylnorleucylleucylphenylalanine to rabbit peritoneal polymorphonuclear leukocytes is increased when sodium ions are removed from the medium. In Hanks' balanced salt solution, the dissociation constant of the binding is about 2 X 10( 8) M, while in Na+-free medium, the dissociation constant is between 3 and 6 X 10(-9) M. Removal of Na+ appears to cause little or no change in receptor number. The change in affinity is rapid and reversible, occurs at 4 degrees C as well as 37 degrees C, and occurs when the Na+ is replaced by K+, choline, or sucrose. The increased binding of low concentrations of peptide is seen on broken as well as whole cells and therefore does not depend on an ion gradient across the membrane. The high affinity receptors are functional in mediating peptide uptake and lysosomal enzyme release. The receptors undergo down-regulation in Na+-free medium, and the dose dependence of the receptor loss is shifted to lower concentrations consistent with the higher affinity of the binding. PMID- 2582047 TI - Lysis of anti-T3-bearing murine hybridoma cells by human allospecific cytotoxic T cell clones and inhibition of that lysis by anti-T3 and anti-LFA-1 antibodies. PMID- 2582049 TI - A Yersinia enterocolitica serotype 0:3 lipopolysaccharide-specific monoclonal antibody reacts more strongly with bacteria cultured at room temperature than those cultured at 37 degrees C. AB - It has been suggested that the O-side chains of the lipopolysaccharide (LPS) of serotype 0:3 strains of Yersinia enterocolitica vary quantitatively and qualitatively depending on whether they are cultured at 37 degrees C or 25 degrees C. It is uncertain whether this affects the expression of the serotype specific antigens that are probably carried on the LPS. We studied this question with a serotype 0:3-specific monoclonal antibody, 2C1. This monoclonal antibody immunoprecipitated a 39K major protein from detergent-solubilized 125I-labeled Yersinia preparation. However, results of Western blot experiments demonstrated that the antigens reactive with 2C1 were not actually the 39K protein but the O side chains of the LPS. Significantly, reactivity could be detected whether the bacteria were cultured at room temperature or at 37 degrees C. However, absorption experiments confirmed that there were less accessible antigenic determinants on the 37 degrees C-LPS. The LPS preparations were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and silver staining. These SDS-PAGE profiles showed that less O-side chains were present in the 37 degrees C-LPS. Hence, the most likely explanation for our observation is that the 37 degrees C incubation condition induced a partial smooth to rough transition of the Yersinia LPS with a decrease in the amount of 2C1-reactive antigen. PMID- 2582050 TI - Identification of cell surface carbohydrate and antigenic changes between noninfective and infective developmental stages of Leishmania major promastigotes. AB - Differentiation of Leishmania major promastigotes from a noninfective to an infective stage has been demonstrated for promastigotes growing within axenic culture and within the sandfly vector. We have been attempting to identify specific biochemical or antigenic changes that are associated with the development of infective-stage promastigotes. In this report we demonstrate that during growth, cultured L. major promastigotes undergo selective changes in surface carbohydrates, determined by their agglutination by plant lectins. Thus, although all promastigotes from logarithmic (log)-phase cultures were agglutinated by the two-D-galactose-binding lectins, peanut agglutinin (PNA) and Ricinus communis, identical concentrations of these lectins failed to agglutinate approximately 50% of L. major promastigotes from the stationary-phase cultures. These changes in lectin-agglutinating properties are consistent with the fact that log-phase promastigotes represent a homogeneous population of noninfective parasites, whereas up to 50% of the stationary-phase organisms appear to be transformed into infective-stage promastigotes, as determined by their ability to survive within normal resident mouse peritoneal macrophages in vitro. The identities of the populations defined by infectivity and PNA agglutination were confirmed by the purification of PNA-unagglutinated promastigotes from stationary phase cultures, which demonstrated that 100% of these promastigotes were able to establish intracellular infections. Lectin-purified, infective-stage promastigotes from the stationary phase were compared with noninfective promastigotes from the log phase for the purpose of identifying stage-specific antigens. On the basis of Western blot analysis and the immunoprecipitation of surface-labeled organisms, we have identified an antigen of roughly 116,000 Mr that is expressed on the surface of infective but not noninfective promastigotes. PMID- 2582051 TI - Identification of herpes simplex virus type 1 (HSV-1) glycoprotein gC as the immunodominant antigen for HSV-1-specific memory cytotoxic T lymphocytes. AB - The frequency and fine specificity of herpes simplex virus (HSV)-reactive cytotoxic T lymphocytes (CTL) of C57BL/6 mice was investigated in limiting dilution culture. The reactivity patterns of virus-specific CTL were assayed on target cells infected with HSV type 1, strain KOS, HSV type 2, strain Mueller, and mutants of HSV-1 (KOS) antigenically deficient or altered in glycoproteins gC or gB, two of the four major HSV-1-encoded cell surface glycoprotein antigens. Most CTL clones recognized type-specific determinants on target cells infected with the immunizing HSV serotype. In addition, the majority of HSV-1-specific CTL did not cross-react with cells infected with syn LD70, a mutant of HSV-1 (KOS) deficient for the presentation of cell surface glycoprotein gC. These data are the first demonstration of the clonal specificity of HSV-1-reactive CTL, and they identify gC as the immunodominant antigen. The fine specificity of gC-specific CTL clones was analyzed on target cells infected with mutant viruses altered in the antigenic structure of gC. These mutants were selected by resistance to neutralization with monoclonal antibodies, referred to as monoclonal antibody resistant (mar) mutants. Most mar mutations in gC did not affect recognition by the majority of CTL clones. This indicated that most epitopes recognized by CTL are distinct from those defined by antibodies. The finding, however, that one mar mutation in gC affected both CTL and antibody recognition of this antigen may help to define antigenic sites important to both humoral and cell-mediated immunity to herpesvirus infection. PMID- 2582052 TI - Analysis of the interaction between a human high molecular weight melanoma associated antigen and the monoclonal antibodies to three distinct antigenic determinants. AB - The restricted tissue distribution and the limited heterogeneity that appear in melanoma lesions of the high M.W. melanoma-associated antigen (HMW-MAA) suggest that this antigen may be an appropriate marker for radioimaging, and a useful target for immunotherapy in patients with melanoma. Therefore, in this study we analyzed other characteristics that are important in the selection of reagents for radioimaging and immunotherapy purposes. The affinities of the monoclonal antibodies (MoAB) 149.53, 225.28S, and 763.74T to distinct determinants of the HMW-MAA were found to be at least 1 X 10(8) mol/L. Furthermore, the effects of the concentrations of unlabeled MoAb on the dissociation rates suggest that the binding of MoAb 149.53 and 225.28S to melanoma cells (Colo 38) is preferentially bivalent, whereas that of MoAb 763.74T is preferentially univalent. These results suggest that the latter MoAb is the reagent of choice for assays that make use of soluble HMW-MAA, whereas the former two are the reagents of choice for assays with membrane-bound HMW-MAA, such as imaging with radiolabeled MoAb. The density of the HMW-MAA on cultured Colo 38 melanoma cells appears to be in the range of approximately 5 X 10(6) molecules/cell. The HMW-MAA was not susceptible to MoAb mediated modulation under a variety of experimental conditions that included various concentrations of modulating MoAb, different incubation times, the use of an anti-mouse Ig antiserum, and the relaxation of equilibrium by diluting cells in MoAb-free medium. These results indicate that the HMW-MAA and the available corresponding MoAb meet the criteria to be reagents for radioimaging and immunotherapy in patients with melanoma. PMID- 2582054 TI - MHC-linked immune response suppression mediated by T cells bearing I-A-encoded determinants. AB - The immune response to chicken egg-white lysozyme (HEL) is actively and specifically regulated by antigen-specific T cell-mediated suppression in mice bearing the H-2b haplotype; the suppression is therefore MHC-linked. In this report, we propose a possible mechanism for MHC-linked suppression of HEL-helper T cells based on expression of I region-encoded cell surface determinants. We determined whether inhibition of anti-HEL antibody responses correlated with expression of serologically detectable I-A-encoded cell surface determinants by antigen-specific helper, suppressor-inducer, or suppressor-effector T cells. It was observed that HEL-suppressor-effector T cells, but not helper or suppressor inducer T cells, were eliminated after treatment with anti-I-Ab antibody and complement. Furthermore, suppressor-effector T cells co-express Thy-1, Lyt-2, and I-A cell surface antigens. These results raise the possibility that HEL-specific helper T cells become functionally inhibited after recognition of HEL and I-A alloantigen displayed by suppressor-effector T cells. Thus, the interaction between helper and suppressor T cells may be analogous to the mechanism of T cell B cell interaction. PMID- 2582053 TI - Distinct proliferative T cell clonotypes are generated in response to a murine retrovirus-induced syngeneic T cell leukemia: viral gp70 antigen-specific MT4+ clones and Lyt-2+ cytolytic clones which recognize a tumor-specific cell surface antigen. AB - After immunization of B6 mice with the syngeneic retrovirus-induced T cell leukemia/lymphoma FBL-3, two major tumor-specific proliferative T cell clonotypes were derived. T cell clones derived from long-term lines propagated by in vitro culture with irradiated tumor cells and syngeneic spleen cells were exclusively of the Lyt-2+ phenotype. Such clones were cytolytic, retained their proliferative phenotype indefinitely when expanded by repeated cycles of reactivation and rest, and recognized a tumor-specific cell surface antigen in association with class I MHC molecules. This tumor cell antigen was not present on nontransformed virus infected cells. Class II MHC-restricted MT4+ clones specific for the viral antigen gp70 were derived from lymph node T cells of FBL-3 tumor-immune mice only by in vitro culture with purified Friend virus in the presence of syngeneic splenic APC. Once derived, however, such clones could be stimulated in the presence of FBL-3 tumor cells and syngeneic spleen cells, demonstrating the reprocessing of tumor-derived gp70 antigen by APC in the spleen cell population. In contrast, no reprocessing of the tumor cell surface antigen by splenic APC for presentation to the class I MHC-restricted T cell clones could be demonstrated. Evidence is presented that FBL-3 T leukemia/lymphoma cells function as APC for Lyt-2+ class I MHC-restricted clones, and that no concomitant recognition of Ia molecules is required to activate these clones. Both Lyt-2+ and MT4+ clones were induced to proliferate in the presence of exogenous IL2 alone, but this stimulus failed to result in significant release of immune interferon. In contrast, antigen stimulation of both clones resulted in proliferation as well as significant immune interferon release. Immune interferon production is not required for the generation of MHC-restricted cell-mediated cytolytic function. PMID- 2582055 TI - Immunoregulation in the rat: characteristics of a suppressor T cell that inhibits antigen-dependent cell proliferation. AB - We have examined the characteristics of a rat suppressor T cell (Ts) that inhibited the antigen-dependent proliferative response of antigen-primed T cells. The kinetics of in vitro induction of Ts from lymph node T cells obtained from antigen-primed rats indicated that Ts were induced in the presence of the priming antigen within 48 hr of culturing. The Ts produced during the first 48 hr of in vitro cultures were radiosensitive (2000 rad) but became partially radioresistant within the next 48 hr of culturing. In the presence but not the absence of priming antigen, Ts inhibited the antigen-dependent proliferative response to the priming antigen as well as to heterologous antigens. Suppression appeared to be mediated via a nondialyzable suppressor factor (TsF). The induction of Ts in cultures required the presence of OX-6-/OX-8- T cells, antigen-presenting cells, and the antigen. Although a majority of cells recovered from the induced cultures were OX-8+, there was no evidence that OX-8+ antigen expression per se was related to Ts activity. Addition of highly purified IL 2 augmented the Ts mediated suppression. The immunoregulatory implications of these findings are discussed. PMID- 2582056 TI - Use of the enzyme-linked immunosorbent assay for measurement of allergen-specific antibodies. AB - A sensitive and specific enzyme-linked immunosorbent assay (ELISA) for allergen specific IgG antibodies is described. Various solid-phase supports (microtiter plates), coating procedures, binding kinetics, and presentation of allergen in the assay were investigated. Using optimal conditions the indirect ELISA, in which the allergen is coated onto the well, was capable of detecting 2.4 ng/ml specific IgG antibodies to bee venom phospholipase A2(PLA2). The sandwich ELISA, in which the allergen was immobilized via specific antibody precoated onto the well, detected 0.24 ng/ml IgG antibodies to PLA2. PMID- 2582057 TI - Hemagglutination assay for human serum fibronectin. AB - A hemagglutination assay for human serum fibronectin (Fn) is described. The assay is based on the capacity of Fn to bind to gelatin. Purified and human serum Fn agglutinate chromic chloride treated sheep red cells coated with gelatin in a quantitative and reproducible manner. The lowest Fn concentration giving positive hemagglutination was found to be 7 micrograms/ml, a sensitivity making it suitable for measurement of Fn in both normal and pathologic sera. The assay is simple and rapid and does not require specialized equipment. PMID- 2582058 TI - Characterisation of monoclonal antibodies to adrenocorticotrophin. AB - We have produced 8 monoclonal antibodies to adrenocorticotrophin (ACTH) derived from immunisation with ACTH (1-24) conjugated to bovine serum albumin or ACTH (1 39) linked to chicken immunoglobulin by a novel method. Antibody specificity was assessed by studying the binding of purified human ACTH, synthetic ACTH (1-24), fragments of ACTH and peptides from the ACTH precursor molecule which have sequence homology. A wide range of specificities was demonstrated. Thus antibody 3H9 recognises the extreme N-terminal sequence (ACTH 4-10), antibody 1A12 is specific for residues 10-18 including alpha MSH, antibody 1D1 is specific for the mid N-terminal sequence but not alpha MSH, and antibody 2A3 is specific for the C terminal portion (ACTH 18-39). These monoclonal antibodies can be easily purified and labelled and their defined specificities make it possible to select antibody combinations which provide the basis for 2-site immunometric assays for ACTH. PMID- 2582059 TI - Monoclonal antibodies to human immune interferon and their use in a sensitive solid-phase ELISA. AB - Two stable hybridoma cell lines secreting specific antibodies against human gamma interferon (HuIFN-gamma) were established. Both monoclonal antibodies (designated as MD-1 and MD-2) belong to the IgG1/kappa subclass and neutralize the antiviral activity of natural and recombinant DNA derived HuIFN-gamma (nHuIFN-gamma and rHuIFN-gamma respectively), although MD-1 is far more effective than MD-2. MD-1 and MD-2 recognize different epitopes and do not compete with each other in binding to HuIFN-gamma as concluded from competition assays. In a 'Western' blot, both antibodies reacted with the 20 kDa and 25 kDa polypeptides present in nHuIFN gamma preparations. A sandwich enzyme immunoassay using microtiter plates coated with unlabeled MD-2 was developed. Biotinylated MD-1 was used as the second antibody. Bound MD-1 was detected by an avidin/alkaline phosphatase enzyme reaction. This immunoassay is highly specific and as sensitive as a bioassay. A radioimmunoassay using MD-2 coated on polystyrene balls and 125I-labeled MD-1 as the second antibody showed a sensitivity comparable to that of the enzyme immunoassay. PMID- 2582060 TI - Fibronectin, as well as other extracellular matrix proteins, mediate human keratinocyte adherence. AB - During the reepithelialization of cutaneous wounds, the migratory epidermis transits over a provisional matrix of fibronectin and fibrin in the absence of laminin and type IV collagen as well as ultrastructurally identifiable basement membrane. Since significant quantities of fibronectin occur at these sites of reepithelialization, we surmised that fibronectin is a suitable substrate for keratinocyte adherence and therefore undertook the in vitro investigations reported here. Purified human plasma fibronectin precoated on bacteriologic microtiter wells was demonstrated to mediate human keratinocyte adherence when concentrations greater than 10 micrograms/ml fibronectin were used. Maximal keratinocyte adherence was obtained in wells precoated with 100 micrograms/ml fibronectin and when cells were incubated with substrate for 60 min or longer at 37 degrees C. Both primary and second-passaged human keratinocytes adhered as well or better to fibronectin than to types I and III collagen, laminin, or type IV collagen under both high- and low-Ca++ culture conditions. However maximal adherence to all substrates occurred when second-passaged keratinocytes were assayed in low-Ca++ medium. Under these latter culture conditions, keratinocyte phenotype resembles the phenotype of cells in the migrating epidermis. To determine specificity of these adherence reactions, antifibronectin antibodies were shown to block keratinocyte adherence to fibronectin but not to laminin substrates. Conversely, antilaminin antibodies blocked adherence to laminin but not fibronectin substrates. Thus, human keratinocytes demonstrate specific adherence to fibronectin in a time- and dose-dependent fashion and this adherence relies on de novo protein synthesis. We take these observations to support our hypothesis that the provisional fibronectin matrix observed beneath the migrating epithelium during tissue repair plays a functional role in the reepithelialization process. PMID- 2582061 TI - Monoclonal antikeratin antibody: production, characterization, and immunohistochemical application. AB - A monoclonal antikeratin antibody, EKH4, was produced from a hybridoma cell line which was established by fusing P3X63SAg8 mouse myeloma cells with spleen cells of mice immunized with human trichilemmoma cells. Immunoblot analysis showed that EKH4 antibody reacts predominantly with 50 kilodalton keratin polypeptide in normal epidermis. By indirect immunofluorescence and immunoperoxidase techniques, EKH4 antibody reacted with the lower 2-3 cell layers of the epidermis as well as most cells of pilosebaceous follicle of human and animal skin. Tumor cells of human basal cell epitheliomas and squamous cell carcinomas were also stained with this antibody. The staining was much more regular and intense compared with an available monoclonal antikeratin antibody, AE1. In the lesion of epidermal proliferative disorders, such as psoriasis and actinic keratosis, the entire epidermis instead of the lower layers was stained with EKH4 antibody. Normal skin overlying or adjacent to epithelial tumors also showed positive staining in the entire epidermis. By using indirect immunoperoxidase technique, EKH4 also stained alcohol-fixed, paraffin-embedded tissue sections. PMID- 2582062 TI - Derivation of Langerhans cell granules from cytomembrane. AB - OKT6 monoclonal antibody has been shown to react selectively with Langerhans cell (LC) cytomembrane in human skin. Taking advantage of this property, we examined the stainability of LC granules with OKT6 using immunoperoxidase method at the ultrastructural level. It was found that the delimiting membranes of LC granules, both attached to the cytomembrane and in the cytoplasm, were specifically stained in the epidermal sheet. These findings suggest that LC granules are derived from invagination of LC cytomembrane and retain T6 antigen. We employed two new methods: one is promotion of endocytosis by incubating the epidermal sheet in tissue culture medium with OKT6 at 4 degrees C and further incubation without OKT6 at 37 degrees C, and the other is the use of saponin to facilitate penetration of the secondary antibody through the cytomembrane of LC. In the LC cytoplasm only the delimiting membrane of the granule was stained; other membranous organelles, such as mitochondria and rough endoplasmic reticulum, did not react. PMID- 2582063 TI - Immunoelectron microscopic identification of upper cytoplasmic antigens on keratin intermediate filaments. PMID- 2582064 TI - Failure of monoclonal antibodies to core glycolipid to bind intact smooth strains of Escherichia coli. AB - To study the ability of antibody to the core glycolipid (CGL) region of lipopolysaccharide (LPS) to bind intact gram-negative bacterial cells, we produced monoclonal antibodies that bind LPS from the Escherichia coli rough mutant J5. Four representative monoclonal antibodies that bound four distinct epitopes on the CGL region of LPS were studied. All four antibodies bound both isolated J5 LPS and intact J5 bacterial cells, but none of the antibodies bound to intact cells of E. coli O111:B4 or K1:O7. Binding of the monoclonal antibodies to isolated LPS from these latter two smooth strains was variable. These results confirm the presence of shared antigenic sites in the CGL region of heterologous LPS molecules but indicate that these sites are not necessarily available on smooth gram-negative bacteria for binding by antibody to CGL. PMID- 2582065 TI - Activation and inhibition of Hageman factor-dependent pathways and the complement system in uncomplicated bacteremia or bacterial shock. AB - Levels of components of the contact activation, coagulation, and complement systems and their main inhibitors were measured in 45 critically ill patients during 61 episodes of uncomplicated bacteremia or bacterial shock. Levels of Hageman factor (factor XII), prekallikrein, high-molecular-weight kininogen, factor XI, factor VII, total hemolytic complement, alternative pathway activity, and C3 were within the normal range during uncomplicated bacteremia (n = 29), but during fatal bacterial shock (n = 13) a significant decrease by 40%-50% was observed in all measurements. During nonfatal bacterial shock (n = 19) a moderate decrease was observed in most of these measurements. The capacity of plasma to inactivate kallikrein was significantly higher during bacteremia than during bacterial shock because of a significant increase in the level of C1 esterase inhibitor. Levels of antithrombin III and alpha 2-macroglobulin were below normal in all groups. Thus increased inhibition of the contact activation and complement systems is beneficial during bacteremia. PMID- 2582066 TI - Seroepidemiological studies of group B Streptococcus type II. AB - In the course of prospective epidemiological studies of group B streptococcal (GBS) colonization and infection, we surveyed 401 paired maternal and cord sera (obtained at delivery) and 23 sera from patients with systemic type II infection for IgG antibody to GBS type II. Type II carriers were more likely to have antibody (greater than 2 micrograms/ml) than were those carrying other GBS types, whereas noncolonized patients were the least likely to have antibody. The overall prevalence of levels of antibody greater than 2 micrograms/ml was estimated to be approximately 6%, on the basis of assay results of the 401 maternal-cord pairs and adjusted for known-colonization status for the entire population of 8,928 deliveries that occurred during the study period. The majority of patients with infection had antibody levels less than 2 micrograms/ml. Five patients, however, had antibody present at levels ranging from 2.7 to 5.8 micrograms/ml. These findings suggest that "antibody deficiency" was widespread and was not by itself a useful determinant of risk for disease caused by GBS type II. PMID- 2582067 TI - Immunoregulation during acute infection with Epstein-Barr virus: dynamics of interferon and 2',5'-oligoadenylate synthetase activity. AB - Immunoregulation during acute infection with Epstein-Barr virus (EBV) is incompletely understood, although species of interferon (IFN) may be important immunoregulatory molecules. IFN, 2',5'-oligoadenylate (2',5'-A) synthetase (an IFN-induced enzyme), T and natural killer cell subsets, and natural and anomalous killer cell functions were studied systemically during acute infectious mononucleosis. Serum IFN was not detected (less than 1 international unit/ml) during infection. 2',5'-A synthetase activity was significantly increased in the acute phase of infection when compared with convalescence (34.5 +/- 6.5 vs. 3.6 +/- 1.2 nmol ATP/mg of protein per hr; P less than .01 by Student's t test). A generalized IFN effect was suggested by elevated 2',5'-A synthetase activity in purified neutrophil preparations. Sequential studies revealed a correlation between peak elevations of 2',5'-A synthetase activity and increased percentages of cytotoxic/suppressor cells as well as anomalous killer cell activity against an EBV-infected B cell line. Thus IFN may act as an immunoregulatory lymphokine early in the course of acute EBV infection. PMID- 2582068 TI - [Structure and expression of the alpha-fetoprotein gene]. PMID- 2582069 TI - [The significance of serum leucine aminopeptidase (P-LAP) determination in the gynecological malignancies]. AB - We determined Placental-Leucine Aminopeptidase (P-LAP) activity, one of the oncodevelopmental antigens, in sera and in tissues of patients with gynecological cancers. The incidence of P-LAP activity and clinical usefulness of the determination of serum P-LAP activity were studied. The mean level in healthy non pregnant sera used as controls was 6.0 +/- 2.4mg/dl/h. The mean level of P-LAP activity in patients with benign tumors such as myoma uteri and benign ovarian tumor did not increase in comparison with the controls. The mean level of P-LAP activity in patients with malignant tumor increased with advancing stages, and especially in advanced cervical and ovarian cancer, serum P-LAP levels were significantly higher than in the controls. Serum P-LAP activity correlated with the serum ferritin concentration (r=0.613), but not with the serum alpha fetoprotein and serum carcinoembryonic antigen concentration. Serial measurements of serum P-LAP activities in patients with gynecological cancer showed that serum P-LAP activity might reflect the progress of cervical and ovarian cancer. Tissue P-LAP activities in 29 ovarian cancers were compared with those in normal tissues. Tissue P-LAP activities in 26 cases out of 29 increased to twice as high as the mean activities in 10 normal ovaries. Our present results suggest the possibility of using P-LAP activity as one of tumor markers for gynecological malignant tumors. PMID- 2582070 TI - Radioimmunolocalization of monoclonal antibodies to human chorionic gonadotropin in choriocarcinoma transplanted into athymic mice. AB - Radioimmunodetection of monoclonal antibodies to human Chorionic Gonadotropin (hCG) or its beta-subunit in choriocarcinoma tissue was investigated in athymic mouse model system. Antibody to hCG exhibited a higher localization index (L.I.) in tumor tissue than those in other organs, but the tissue/blood ratio of this antibody in tumor tissue was not so high as expected (0.38 and 0.5 on Day 2 and 5 respectively). On the other hand, antibody to beta-subunit showed the same L.I. in tumor tissue as those in other organs. Gel filtration of serum of mouse given an antibody to hCG showed that the antibody was forming immune complexes in the blood stream. Autoradiography showed many grains in the capillary vessels and intercellular spaces in the tumor tissue. We concluded that a monoclonal antibody to hCG localized in choriocarcinoma tissue via a mechanism of retention of immune complexes in the tissue, and that there may be a limitation to the clinical application of localization of antibodies to secretory products such as hCG of tumor cells from their low specific localization. PMID- 2582071 TI - [A clinical and histopathological study of anticancer effect of treatment with bleomycin alone--with particular reference to histological disappearance of primary lesion]. PMID- 2582073 TI - [Estimation of the ventricular activation sequence in normal and ventricular premature beat by body surface isochrone map (VAT map)]. PMID- 2582072 TI - [Experimental and clinical studies on embolotherapy of lung cancer]. PMID- 2582075 TI - Morphology of identified neurosecretory and non-neurosecretory cells in the cockroach pars intercerebralis. AB - Electrophysiologically identified cells of the cockroach pars intercerebralis (Periplaneta americana) were injected with the dye Lucifer Yellow for morphological examination and with horseradish peroxidase for ultrastructural marking. In addition to this, uninjected cells were also studied to elaborate the findings from the injected material. The two electrophysiologically distinct classes of cells (type I and type II) correspond to two distinct morphological and ultrastructural classes. Type I cells are the medial neurosecretory cells of the pars intercerebralis, which project their axons to the retrocerebral neuro hemal complex. Their cell bodies have a mean diameter of 17 microns, and they contain neurosecretory granules 200 nm in diameter. Arborizations emanate from the axon in the anterior part of the protocerebral neuropil. The type II cell bodies are larger (38 microns in diameter). Their axons project into the contralateral circumesophageal connective. These cells were usually multipolar, having somatic arborizations in the anterior portocerebral neuropil. The cell bodies contain vesicles 40 nm in diameter, numerous trophospongia, and a multi layered glial envelope. PMID- 2582074 TI - Histological studies of vascularised nerve graft and conventional nerve graft. AB - Histological studies of vascularised nerve graft versus conventional nerve graft were performed in eighteen rat femoral nerves using microsurgical technique. This experiment showed that there was no difference in the degree of vascularisation, reticulin framework collapse, rate and extent of axonal regeneration and remyelination between the two groups. PMID- 2582076 TI - Interactions of organic calcium channel antagonists with calcium channels in single frog atrial cells. AB - Inhibition of whole-cell calcium currents in enzymatically dispersed frog atrial myocytes by D-600, diltiazem, and nifedipine was studied using a single micropipette voltage-clamp technique. The objective of these experiments was to test the applicability of a modulated-receptor hypothesis similar to that proposed for local anesthetic interactions with sodium channels to account for the tonic and frequency-dependent interactions of these organic compounds with myocardial calcium channels. Data consistent with such a hypothesis include: (a) prominent use-dependent block of iCa by D-600 and diltiazem, which are predominantly charged at physiological pH; (b) iCa block by an externally applied, permanently charged dihydropyridine derivative is greatly attenuated; (c) all three antagonists produce large negative shifts in the voltage dependence of iCa availability; (d) block of iCa by these compounds is state-dependent; (e) reactivation of iCa in the presence of all three antagonists is biexponential, which suggests that drug-free channels recover with a normal time course and drug bound channels recover more slowly; and (f) the kinetics of the drug-induced slow iCa recovery process may be determined largely by factors such as size and molecular weight, in addition to lipid solubility of the compounds. Experiments in which the pH was modified, however, reveal some important differences for the interaction of organic calcium antagonists with myocardial calcium channels. Acidification, in addition to changing the proportion of charged and neutral antagonist in solution, was found to selectively antagonize tonic inhibition of iCa by diltiazem and nifedipine, without changing the kinetics of the drug induced slow iCa reactivation process. It is concluded that two distinct receptor sites may be involved in block of iCa by some of these compounds: a proton accessible site and a proton-inaccessible site. PMID- 2582077 TI - An ion's view of the potassium channel. The structure of the permeation pathway as sensed by a variety of blocking ions. AB - We have studied the block of potassium channels in voltage-clamped squid giant axons by nine organic and alkali cations, in order to learn how the channel selects among entering ions. When added to the internal solution, all of the ions blocked the channels, with inside-positive voltages enhancing the block. Cesium blocked the channels from the outside as well, with inside-negative voltages favoring block. We compared the depths to which different ions entered the channel by estimating the "apparent electrical distance" to the blocking site. Simulations with a three-barrier, double-occupancy model showed that the "apparent electrical distance," expressed as a fraction of the total transmembrane voltage, appears to be less than the actual value if the blocking ion can pass completely through the channel. These calculations strengthen our conclusion that sodium and cesium block at sites further into the channel than those occupied by lithium and the organic blockers. Our results, considered together with earlier work, demonstrate that the depth to which an ion can readily penetrate into the potassium channel depends both on its size and on the specific chemical groups on its molecular surface. The addition of hydroxyl groups to alkyl chains on a quaternary ammonium ion can both decrease the strength of binding and allow deeper penetration into the channel. For alkali cations, the degree of hydration is probably crucial in determining how far an ion penetrates. Lithium, the most strongly hydrated, appeared not to penetrate as far as sodium and cesium. Our data suggest that there are, minimally, four ion binding sites in the permeation pathway of the potassium channel, with simultaneous occupancy of at least two. PMID- 2582079 TI - Evidence for conformational changes of poliovirus precursor particles during virus morphogenesis. AB - Antisera raised against isolated structural polypeptides VP1, VP2 and VP3 of poliovirus type 1, strain Mahoney, reveal a differential reaction against mature virus and its precursor particles. During virus morphogenesis antigenic sites recognized by VP1 and VP2 antisera are lost stepwise from the surface of precursor particles. These sites are cross-reacting between serotypes and are also lost from precursor particles of type 2 (MEF-1) and type 3 (Saukett). They are absent on the surface of mature virus of all three serotypes. In contrast, the VP3 antiserum recognizes sites expressed maximally on the surface of infectious virus of type 1 (Mahoney). This antiserum did not show significant intertypic cross-reactions with virus particles, empty capsids or 14S particles of poliovirus types 2 and 3. However, it does recognize intertypic cross-reacting sites, like the VP1 and VP2 antisera, on denatured polypeptides and 5S particles of each serotype. PMID- 2582078 TI - Modulation of calcium channels by norepinephrine in internally dialyzed avian sensory neurons. AB - Modulation of voltage-dependent Ca channels by norepinephrine (NE) was studied in chick dorsal root ganglion cells using the whole-cell configuration of the patch clamp technique. Cells dialyzed with K+ and 2-10 mM EGTA exhibited Ca action potentials that were reversibly decreased in duration and amplitude by NE. Ca channel currents were isolated from other channel contributions by using: (a) tetrodotoxin (TTX) to block gNa, (b) internal K channel impermeant ions (Cs or Na/N-methylglucamine mixtures) as K substitutes, (c) external tetraethylammonium (TEA) to block K channels, (d) internal EGTA to reduce possible current contribution from Ca-activated channels. A marked decline (rundown) of Ca conductance was observed during continual dialysis, which obscured reversible NE effects. The addition of 2-5 mM MgATP to the intracellular solutions greatly retarded Ca channel rundown and permitted a clear assessment of modulatory drug effects. The inclusion of an intracellular creatine phosphate/creatine phosphokinase nucleotide regeneration system further stabilized Ca channels, which permitted recording of Ca currents for up to 3 h. NE reversibly decreased both steady state Ca currents and Ca tail currents in Cs/EGTA/MgATP-dialyzed cells. A possible role of several putative intracellular second messengers in NE receptor-Ca channel coupling was investigated. Cyclic AMP or cyclic GMP added to the intracellular solutions at concentrations several orders of magnitude higher than the Kd for activation of cyclic nucleotide-dependent protein kinases did not block or mask the expression of the NE-mediated decrease in gCa. Addition of internal EGTA to a final concentration of 10 mM also did not affect the expression of the NE response. These results suggest that neither cyclic AMP nor cyclic GMP nor Ca is acting as a second messenger coupling the NE receptor to the down-modulated Ca channel population. PMID- 2582080 TI - Purification of herpes simplex virus glycoproteins B and C using monoclonal antibodies and their ability to protect mice against lethal challenge. AB - Monoclonal antibodies which react with herpes simplex virus type 1 (HSV-1) glycoproteins, but do not neutralize infectivity, were prepared. The protein to which each monoclonal antibody was directed was determined by various techniques including their reaction with polypeptides from glycoprotein-deficient mutants after protein blotting, and also tests using passive haemagglutination. Monoclonal antibodies A7 and alpha C3 were directed against a type-specific determinant on gC and a type-common determinant on gB respectively. In addition, A7 reacted only with the HFEM strain of HSV-1 and did not react with any of the 20 low-passage human isolates also tested. The monoclonal antibodies were used in immunoadsorption chromatography to purify individual glycoproteins from detergent extracts of HSV-1-infected cells. The ability of the monoclonal antibodies or purified glycoproteins to protect mice against a lethal encephalitis induced by intracerebral inoculation of HSV-1 was investigated. Passive immunization was not very effective; however, purified gC or a mixture of gB and its precursor pgB induced good levels of neutralizing antibody which persisted for at least 9 weeks and mice survived virus challenge. PMID- 2582081 TI - Injection of anti-thy-1.2 serum breaks genetic resistance of mice against herpes simplex virus. AB - Nude mice have been shown to be as resistant to intraperitoneal infection with herpes simplex virus type 1 (HSV) as their heterozygous littermates. Here we document that both activation of natural killer (NK) cells and interferon induction were normal in nu/nu mice after injection of HSV. Injection of silica caused increased mortality by HSV in C57BL/6 mice. Silica, in addition, led to a significant reduction of NK cell activity but had no effect on the interferon response. Treatment of C57BL/6 mice with anti-asialo GM1 (an antiserum with a predominant effect on NK cells) caused complete abolition of the NK cell response, but had no effect on interferon induction or virus-induced mortality. In further studies a monoclonal anti-thy-1.2 antibody was utilized which possessed high activity in vivo in depleting T cell responses in mice. Injection of anti-thy-1.2 decreased NK cell activation but was without effect on the interferon response. Unexpectedly, in view of the data in nu/nu mice, this antibody increased HSV-induced mortality in C57BL/6 mice. Similar data were obtained when anti-thy-1.2 was injected into nu/nu mice. Our results are compatible with the hypothesis that T cell precursors sensitive to anti-thy-1.2 present in homozygous nude mice play a role in resistance against HSV. Furthermore, the data in the euthymic mice may indicate a role of T cells in the primary resistance of mice against HSV. PMID- 2582082 TI - Characterization of interferon induction in mice of resistant and susceptible strains during murine cytomegalovirus infection. AB - Comparison of the induction of plasma interferon (IFN) by murine cytomegalovirus (MCMV) in BALB/c and CBA mice demonstrated similar kinetics of induction with maximum titres at 6 and 48 h after infection. Although neutralized by antibody to type I (alpha and beta) IFN, the IFN was predominantly acid-labile. The 6 h titre was markedly dependent upon the dose and method of preparation of MCMV and also the strain of mouse used. Higher plasma IFN titres were found in CBA than in BALB/c mice following both intraperitoneal or intravenous infection but this strain variation was not apparent in IFN levels in the spleen and liver. IFN induced by MCMV in CBA and BALB/c mice was equally effective at inhibiting MCMV replication in vitro. Cultured embryo fibroblasts derived from CBA and BALB/c mice produced similar levels of IFN, but it was not detected until 24 h after infection. Use of irradiation chimeras prepared from H-2-compatible high IFN producers (CBA) and low producers (B10.BR) showed that the level of IFN produced at 6 h was dependent upon bone marrow-derived cells. PMID- 2582083 TI - Identification of Epstein-Barr virus-induced polypeptides in P3HR-1 cells by protein immunoblot. AB - The protein immunoblot technique was used to identify Epstein-Barr virus-specific antigens present in sodium butyrate-induced P3HR-1 cells. Using sera from patients with either nasopharyngeal carcinoma or arthritis, 16 polypeptides were detected ranging in molecular weight from 22K to 140K. Each of the anti-EA-, anti VCA-positive sera were found to contain antibodies to different subsets of the antigens. A 72K protein was identified which was consistent with the nuclear antigen (EBNA), and culturing cells in the presence of disodium phosphonoacetate allowed identification of 140K and 22K antigens as late viral products. Treatment of cells with sodium butyrate revealed that expression of some antigens increased in parallel with the time of incubation of the cells in butyrate while other antigens either appeared early and then decreased in intensity or were only present after a number of days of butyrate treatment. One of the antigens which decreased with the time cells were treated with butyrate was EBNA. PMID- 2582084 TI - Principal and subsidiary antigenic sites of VP1 involved in the neutralization of poliovirus type 3. AB - The characterization of over 300 mutants, derived from two strains of poliovirus type 3 and selected for resistance to neutralization by monoclonal antibodies, has led to the further definition of the major antigenic site involved in neutralization. The site encompasses amino acids 89 to 100 of VP1. A subsidiary antigenic site near the C-terminus of VP1 has been identified for the Sabin vaccine strain of poliovirus type 3. Of 59 monoclonal antibodies to poliovirus type 3 examined, 27 had virus-neutralizing activity and 25 of these were identified as directed against the major site on VP1 (designated site 1), indicating the immunodominant role of this site. One of the six monoclonal antibodies that recognized the subsidiary antigenic site on VP1 (designated site 2) possessed virus-neutralizing activity. The identification of the principal antigenic site of the virus provides a rational basis for attempts at the development of synthetic oligopeptide vaccines against poliovirus type 3. PMID- 2582085 TI - cDNA cloning of the nucleocapsid and nucleocapsid-associated protein genes of mumps virus. AB - cDNA clones of the mumps virus N and P messenger RNAs were isolated from an infected cell cDNA library. The N and P clones selected the two predominant polyadenylated RNAs found in mumps virus-infected cells with mol. wt. of 0.69 X 10(6) and 0.51 X 10(6), respectively. In addition, clones of the P gene hybridized to and selected mRNAs of higher mol. wt. probably representing polycistronic transcripts of the mumps genome. Hybrid-select translation experiments confirmed the specificity of the clones as representing the nucleocapsid (N) and nucleocapsid-associated protein (P) genes. PMID- 2582086 TI - Protein phosphorylation and neuronal function. AB - Studies in the past several years have provided direct evidence that protein phosphorylation is involved in the regulation of neuronal function. Electrophysiological experiments have demonstrated that three distinct classes of protein kinases, i.e., cyclic AMP-dependent protein kinase, protein kinase C, and CaM kinase II, modulate physiological processes in neurons. Cyclic AMP-dependent protein kinase and kinase C have been shown to modify potassium and calcium channels, and CaM kinase II has been shown to enhance neurotransmitter release. A large number of substrates for these protein kinases have been found in neurons. In some cases (e.g., tyrosine hydroxylase, acetylcholine receptor, sodium channel) these proteins have a known function, whereas most of these proteins (e.g., synapsin I) had no known function when they were first identified as phosphoproteins. In the case of synapsin I, evidence now suggests that it regulates neurotransmitter release. These studies of synapsin I suggest that the characterization of previously unknown neuronal phosphoproteins will lead to the elucidation of previously unknown regulatory processes in neurons. PMID- 2582087 TI - Sequential limited proteolysis of myelin basic protein by neutral protease activities of bovine brain. AB - Acid extracts of delipidated white matter of bovine brain were prepared, and their proteolytic activities toward myelin basic protein (MBP) were evaluated at pH 3 and pH 7. This was done by measuring changes in total protein using a selective dye-binding assay, and by evaluating peptide patterns by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and densitometry. At pH 7 greater than 50% of total protein and about 75% of MBP were degraded after 48 h, whereas at pH 3 it was less than 20% altogether. Neutral proteolysis of MBP entailed up to 12 different proteolytic peptide fragments in the molecular weight range of 17.5 to 6 kd. Its enzymatic nature was verified using protease inhibitors, including N ethylmaleimide, phenylmethylsulfonyl fluoride, o-phenanthroline, and EDTA, as well as pepstatin A and alpha 2-macroglobulin. Both transient changes in percentages of some intermediate peptides and differential effects of individual inhibitors on electrophoretic peptide patterns strongly suggest a sequential type of limited proteolysis. The results also indicate that acid extracts contained several endopeptidases of which a cysteine protease appears to initiate the breakdown of MBP. PMID- 2582088 TI - Characterization of FMRF amide-like immunoreactivity in rat spinal cord by region specific antibodies in radioimmunoassay and HPLC. AB - Material in rat spinal cord extracts that reacts with antibodies to the molluscan tetrapeptide FMRF amide (Phe-Met-Arg-Phe-NH2) has been characterized by HPLC and radioimmunoassay using region specific antibodies. An antibody to the N terminally extended analogue, Tyr-Gly-Gly-Phe-Met-Arg-Phe-NH2 (YGGFMRF amide), did not react with the rat material. Two antibodies to FMRF amide were characterized that differed markedly in their affinities for analogues with substitutions in the second and third positions from the C-terminus; both required the C-terminal amide, and neither showed appreciable sensitivity to substitutions in the fourth position from the C-terminus. With both antibodies the relative potency of the avian brain peptide, LPLRF amide, was about 0.1. Both antibodies revealed similar concentrations of immunoreactive material in rat spinal cord extracts. On reversed-phase HPLC using Techsil C18 and Spherisorb phenyl columns, two peaks were separated that could be distinguished in retention times from FMRF amide, Leu-Pro-Leu-Arg-Phe-NH2 (LPLRF amide), and YGGFMRF amide. The results suggest that the rat spinal cord peptides are structurally related to the C-terminal tripeptide of FMRF amide and are probably extended at the N terminus by sequences immunochemically distinct from other known peptides. PMID- 2582090 TI - Characterization of quinolinic acid phosphoribosyltransferase in human blood and observations in Huntington's disease. AB - Quinolinic acid (QUIN), an excitotoxic compound present in the mammalian CNS and periphery, has been hypothetically linked to human neurodegenerative disorders such as Huntington's disease and epilepsy. Quinolinic acid phosphoribosyltransferase (QPRT), the catabolic enzyme of QUIN, is found in the CNS and peripheral organs where it may be a major influence on the tissue levels of QUIN. We have measured QPRT activity in human blood as a means of assessing one aspect of QUIN metabolism in humans. The enzyme was present in blood cells, platelets having a sixfold greater activity than erythrocytes, but was essentially absent from the plasma. In a blood cell fraction, enzyme activity was potently inhibited by phthalic acid (IC50 = 6.1 microM). Kinetic analyses conducted over a range of QUIN concentrations yielded Km values of 1.89-3.75 microM and Vmax values of 33.4-72.5 fmol nicotinic acid mononucleotide/h/mg protein. Enzyme activity varied 2.2-fold between normal individuals, was reasonably constant over a series of sampling intervals, and showed some diminution when blood was stored for 1 month at -20 degrees C. No differences of enzyme activity in erythrocytes or platelets were apparent between three Huntington's disease patients and their unaffected spouses. These data indicate that measurements of QPRT activities in blood are a convenient means to monitor QUIN metabolism in human subjects and that a deficiency of the enzyme is not apparent in Huntington's disease. PMID- 2582091 TI - Parvalbumin in human brain. AB - Parvalbumin was isolated from human cerebral cortex and biceps and triceps muscles by HPLC. The immunological properties of the human protein and the mobility in two-dimensional polyacrylamide gels were similar to that of parvalbumin isolated from the muscles of rat, mouse, rabbit, and chicken. The tryptic peptide maps of the human parvalbumin, however, differed considerably from all other parvalbumins, indicating a distinct primary structure. The immunolabeled cells in the hippocampus of the human brain were of different sizes and forms; they occurred in all subfields and probably represent interneurons. PMID- 2582089 TI - Regulation of cerebroside and sulfatide metabolism in glia cells. AB - Mouse oligodendroglioma cells, G-26 clone 20 and 24, contain galactosylceramide (cerebroside) and sulfogalactosylceramide (sulfatide) as determined by an HPLC technique. The synthesis of both these lipids was stimulated by 10(-6) M hydrocortisone (cortisol) and also by the removal of serum from the culture medium. Forty-eight hours after the addition of cortisol the incorporation of H235SO4 into sulfatide, the level of sulfatide and the specific activity of the enzyme 3'-phosphoadenosine 5'-phosphosulfate:galactosylceramide sulfotransferase in the cells increased three- to fourfold. The level of cerebroside and the specific activity of UDP-galactose:hydroxyacyl sphingosine galactosyltransferase also increased threefold in the cells on treatment with cortisol. The effect of the hormone on the synthesis of cerebroside preceded the increase in sulfatide synthesis. Experiments with cycloheximide and actinomycin D showed that the effect of the hormone on glycolipid synthesis in these cells were mediated through de novo messenger RNA and protein synthesis. Removal of serum from the culture medium resulted in an approximately twofold enhancement of H235SO4 incorporation into sulfatide within 24 h. The levels of sulfatide and cerebroside and the specific activity of the galactosyltransferase and sulfotransferase also increased significantly after serum removal. However, in contrast to the effect of the steroid, the sulfotransferase activity and the level of sulfatide increased prior to elevations in galactosyltransferase and cerebroside. The effect of serum removal was also found to be mediated by de novo RNA and protein synthesis. The effects of cortisol and serum removal on the synthesis of cerebroside and sulfatide were strictly additive. PMID- 2582092 TI - Phylogenetic survey of proteins related to synapsin I and biochemical analysis of four such proteins from fish brain. AB - A phylogenetic survey of proteins immunologically related to Synapsin I, a major synaptic vesicle-associated phosphoprotein in mammals was carried out. Proteins antigenically related to Synapsin I were found by use of radioimmunoassay and other radioimmunochemical techniques in the nervous systems of several vertebrate and invertebrate species, which included birds, reptiles, amphibians, fish, echinoderms, arthropods, and mollusks. Four proteins present in fish brain, antigenically related to Synapsin I, were further studied and found to resemble mammalian Synapsin I in several respects. Like Synapsin I, the fish proteins were present in high amounts in nervous tissue, were enriched in synaptosomal fractions of brain where they were substrates for endogenous protein kinases, were acid extractable, and were sensitive to digestion by collagenase. In addition, two-dimensional peptide-mapping analysis revealed some homology between major phosphopeptide fragments of Synapsin I and the fish proteins. The results indicate that proteins related to Synapsin I are wide-spread in the animal kingdom. PMID- 2582093 TI - Calcium channel antagonism by pizotifen. AB - Pizotifen is a clinically effective anti-migraine agent with potent anti serotonin and anti-histamine properties. Pizotifen is equipotent in blocking contractions of the canine basilar artery induced by serotonin, norepinephrine or calcium chloride. As a result, the primary action of pizotifen in the canine basilar artery system appears to be calcium channel blockade and not selective antagonism of serotonin or norepinephrine. Calcium channel blocking ability may be related to the clinical efficacy of pizotifen in the treatment of migraine. PMID- 2582094 TI - Spared musical abilities in a conductor with global aphasia and ideomotor apraxia. AB - A conductor suddenly developed global aphasia and severe ideomotor apraxia as a result of an infarct in the territory of the left middle cerebral artery. Although aphasia and apraxia remained unchanged during the following six years, his musical capacities were largely spared and he was still able to conduct. This case provides some evidence in favour of right hemisphere dominance for music. PMID- 2582096 TI - A descriptive study of the practice of community health nurses with infants at risk for developmental disabilities. PMID- 2582095 TI - Reactivity of sera and isolated monoclonal IgM from patients with Waldenstrom's macroglobulinaemia with peripheral nerve myelin. AB - Sera of 23 patients with Waldenstrom's macroglobulinaemia and six monoclonal IgM paraproteins, which had been isolated from these sera, were examined for reactivity against peripheral nerve tissue. Of these 23 patients, 12 had clinical signs of peripheral polyneuropathy (PN). Using an indirect immunofluorescence method, all sera and monoclonal IgM preparations reacted with peripheral nerve structures, displaying a distinct granular fluorescence pattern with anti-IgM sera. The Waldenstrom sera reacted mainly with structures at the border of the myelin sheath, as well as between myelin and axon, and occasionally with the axon itself. There was no difference between sera of patients with PN and those without. Negative results were obtained in a complement fixation assay. Of the 23 sera, 15 reacted in an antibody-dependent lymphocyte-mediated cytotoxicity reaction (ADLC) with peripheral nerve myelin, and to a much lesser extent with myelin basic protein from CNS. Five of the six isolated monoclonal IgM preparations also gave positive ADLC reactions. These results constitute additional evidence for an immunological mechanism in the pathogenesis of PN in Waldenstrom's macroglobulinaemia. PMID- 2582097 TI - Successful treatment of resistant germinal neoplasms with VP-16 and cisplatin: results of a Southeastern Cancer Study Group trial. AB - Between July 1979 and May 1982, we treated 45 male patients with refractory germinal neoplasms. All patients had previously received intensive cisplatin containing combination chemotherapy regimens. Patients received salvage chemotherapy with VP-16 and cisplatin +/- bleomycin +/- doxorubicin. Of 44 evaluable patients, 19 (43%) achieved complete remissions with salvage chemotherapy, 12 (27%) had partial remissions, and nine (21%) had no response. Four patients (9%) were not evaluable for response due to early death or noncompliance but are considered treatment failures. Ten patients (23%) remain alive and continuously disease free 20 to 39 months (median, 29 months) after completion of therapy. Hematologic toxicity was severe, with one death related to sepsis. Bleomycin-induced pulmonary fibrosis occurred in 17 patients with two fatalities. The addition of bleomycin and/or doxorubicin to this regimen increases toxicity and probably does not improve treatment results. Salvage chemotherapy with VP-16 and cisplatin offers potentially curative therapy to men with resistant germinal tumors. PMID- 2582098 TI - Transient voltage and calcium-dependent outward currents in hippocampal CA3 pyramidal neurons. AB - Membrane currents activated by step changes in membrane potential were studied in hippocampal pyramidal neurons of region CA3 using the single microelectrode voltage-clamp technique. The transient outward current activated by depolarizing steps appeared to be composed of two transient currents that could be distinguished by differences in voltage sensitivity, time course, and pharmacological sensitivity. The more slowly decaying current was activated by voltage steps positive to -60 mV and declined exponentially with a time constant between 200 and 400 ms. This current inactivated as the holding potential was made more positive over the range of -75 to -45 mV and was 50% inactivated near 60 mV. The more slowly decaying transient current was selectively blocked by 0.5 mM 4-aminopyridine (4-AP) but not by 5-10 mM tetraethylammonium (TEA) or 2-5 mM Mn2+. The second transient current had a much faster time course than the 4-AP sensitive current, having a duration of 5-20 ms. This very fast transient current was observed during potential steps positive to -45 mV. The fast transient current was inactivated when the holding potential was made positive to -45 mV. The amplitude of the fast transient current was greatly reduced by the application of 4 mM Mn2+ or Ca2+-free artificial cerebrospinal fluid (CSF). The fast transient current appeared to be unaffected by 0.5 mM 4-AP but was greatly reduced by 10 mM TEA. These results suggest that the transient outward current observed during depolarizing steps is composed of at least two distinct transient currents. The more slowly decaying current resembles the A-current originally described in molluscan neurons (9, 32, 42) in voltage sensitivity, time course, and pharmacological sensitivity. The faster transient current resembles a fast, Ca2+-dependent transient current previously observed in bull-frog sympathetic neurons (5, 27). PMID- 2582099 TI - Muscle-fiber compartmentalization in cat splenius muscles. AB - Splenius is a structurally complex muscle that is supplied by nerves from four cervical segments. We have examined the architectural organization of extrafusal fibers in splenius by microdissecting muscles stained "en bloc" with gold chloride. We also analyzed the distribution of motor units supplied from different cervical segments using the glycogen-depletion technique. Microdissections show that the fiber architecture of splenius is different in medial and lateral muscle parts. In medial splenius, muscle fascicles run uninterrupted from the muscle origin to insertion, while in lateral splenius, separate compartments of muscle fascicles are linked in series by two tendinous inscriptions. In muscle fascicles longer than 2.0 cm, many extrafusal fibers do not run the whole length of the fascicle. Instead, these fibers end intramuscularly by tapering to a fine strand that is closely adherent to adjacent extrafusal fibers. Less than 1% of extrafusal fibers in splenius exceeds 3.0 cm in length. Experiments using glycogen depletion showed that nerves from different spinal segments innervate different muscle regions. Nerves from C1 supply muscle fibers in a small rostromedial zone. Nerves from C2-C4 have motor domains that extend from the medial to the lateral muscle edge and are arranged in series. In lateral splenius, the motor domains are separated by tendinous inscriptions. In medial splenius, where no inscriptions are present, the motor domains of adjacent segmental nerves have overlapping boundaries due to the extensive interdigitation of motor units supplied from different segmental nerves. A single muscle fascicle in medial splenius is commonly composed of two sets of fibers supplied by adjacent segments that are distributed at opposite ends of the fascicle and interdigitate in midregions of the fascicle. The in-series compartmentalization of splenius has important implications for its motor control. To secure effective muscle shortening or tension development, central mechanisms may be required to coordinate the recruitment of in-series motor units. The presence of many short fibers with intramuscular insertions leads us to question how contractile forces are developed and transmitted in splenius and other mammalian muscles that are composed of short, in-series fibers. PMID- 2582100 TI - Structure of axon terminals and active zones at synapses on lizard twitch and tonic muscle fibers. AB - The freeze-fracture technique was used to study differences in membrane structure which could explain differences in the number of quanta released from axon terminals on twitch and tonic muscle fibers in Anolis intercostal muscles. The protoplasmic leaflets of axon terminals facing lizard twitch muscle fibers have intramembrane particle specializations characterized by two parallel linear particle arrays each composed of two particle rows which lie perpendicular to the axis of shallow ridges in the axolemma. During K+ depolarization, vesicles open between the arrays, confirming that these structures are the active zones for synaptic vesicle opening. Active zones at axon terminals on tonic fibers are defined by one linear particle array composed of two parallel particle rows oriented along the axis of a shallow presynaptic ridge; vesicles open beside these arrays. Thus, there are more particles near active zone vesicles in terminals on twitch fibers. Even though terminals on twitch and tonic muscle fibers seem to have similar numbers of synaptic vesicles associated with their active zones, a presynaptic action potential is reported to release at least 10 times more quanta from terminals on twitch fibers. We postulate that the differences in quantal output are related to the observed differences in the number of active zone particles flanking synaptic vesicles at the active zone. Indeed, the correlation between the distribution of these particles and the level of transmitter release provides additional support for the idea that they are the calcium channels which couple transmitter release to the action potential. PMID- 2582101 TI - Genetic modifications of voltage-sensitive sodium channels in Drosophila: gene dosage studies of the seizure locus. AB - We have identified a genetic locus in Drosophila melanogaster whose product appears to have a structural role in the formation of functional voltage sensitive sodium channels. This locus, designated seizure, is defined by two temperature-sensitive alleles (seits-1 and seits-2), each of which causes convulsive seizures followed by a rapid but reversible paralysis of adults at restrictive temperatures above 38 degrees C. Previous work had shown that seits-2 extracts display an altered pH dependence and an abnormally high Kd for [3H] saxitoxin binding at high temperatures, suggesting that sodium channels in seits 2 mutants have an altered structure (Jackson F. R., S. D. Wilson, G. R. Strichartz, and L. M. Hall (1984) Nature 308: 189-191). These binding studies have now been extended to extracts of seits-1 which have a Kd not significantly different from wild-type at all assay temperatures. However, seits-1 extracts show a reduced number of saxitoxin binding sites (Bmax) relative to wild-type. This reduction is only 5 to 18% at 0 degree C but is 17 to 37% at 39 degrees C, suggesting that under certain conditions sodium channels in the seits-1 mutant are more labile than those of wild-type. Cytogenetic studies demonstrate that the seizure locus maps within region 60A to 60B8-10 on the second chromosome. Gene dosage analysis of approximately 99.7% of the genome, including this second chromosome region, failed to detect a wild-type locus whose dose affected saxitoxin-binding activity. Nevertheless, the mutant seits-2 allele has codominant and dose-dependent effects on paralytic behavior and saxitoxin-binding activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582102 TI - Characterization and segmental distribution of 125I-Bolton-Hunter-labeled substance P binding sites in rat spinal cord. AB - Substance P (SP) is widely distributed in the spinal cord and has been implicated as a neurotransmitter in several spinal cord neuronal systems. To investigate SP receptors in the spinal cord, 125I-Bolton-Hunter-SP (125I-BH-SP) was used to identify and characterize spinal cord binding sites for the peptide. The binding of 125I-BH-SP had the following characteristics: high affinity; time, temperature, and membrane concentration dependent; reversible; and saturable. The IC50 of SP in whole spinal cord was 0.46 nM as compared with 0.95, 60, and 150 nM for physalaemin, eledoisin, and kassinin. Four putative antagonists of SP were less than 0.0001 times as potent as SP in inhibiting 125I-BH-SP binding. IC50s were 5, 7.5, 7.0, and 45 microM for D-Pro2, D-Trp7,9-SP; D-Pro2, D-Phe7, D-Trp9 SP; D-Arg1, D-Pro2, D-Trp7,9, Leu11-SP; and D-Pro4, D-Trp7,9,10-SP(4-11), respectively. The lumbosacral section bound 3 times more SP than the cervical and thoracic sections, although IC50 for the cervical section was 0.06 of that for the lumbosacral and thoracic sections. The data suggest more than one class of binding site for SP in the spinal cord and indicate a direct role for SP in spinal cord functions. PMID- 2582104 TI - Gingival keratinocytes express HLA-DR antigens in chronic gingivitis. AB - The expression of the histocompatibility antigens HLA-DR and HLA-A, B, C within periodontally diseased tissue was investigated using immunohistological and histochemical techniques. Tissue was obtained from 18 patients with periodontal disease and from 2 healthy volunteers. HLA-DR antigen was expressed by the keratinocytes of the oral epithelium in all inflamed samples but was not a feature of normal tissue where HLA-DR reactivity was confined to Langerhans cells. These results are consistent with an underlying cellular immune process. Using a variety of phenotypic markers it was possible to characterize the macrophage population within the connective tissue into 2 distinct types: an antigen-presenting cell type located subjacent to the oral epithelium and a phagocytic cell type situated deep within the connective tissue. PMID- 2582103 TI - Digestion and absorption of carbohydrates in fowl and events through perinatal development. AB - Starch is the main carbohydrate in the food of poultry. Starch granules are digested by pancreatic alpha-amylase in the small intestine. Intestinal villi have enterocytes that project microvilli with a fibrous glycocalyx from the surface. These fine structures are envisaged to entrap water that is mixed with mucin from nearby goblet cells to form the "unstirred water layer." Maltose, maltotriose and alpha-limit dextrins must diffuse across this first barrier to absorption to be hydrolyzed by maltase and sucrase-isomaltase immobilized at the membrane; however, the resultant glucose, once formed, accrues at the surface to provide a concentration advantage. Fowl adjust to changes in dietary starch by altering the amount of amylase released, intestinal surface area and enterocyte carbohydrase concentration. Enterocytes arising during embryonic development have no carbohydrases and are not involved with glucose absorption, but they appear to be specialized for maternal immunoglobin transfer in ovo. Embryonic villi are stimulated by transfer activity, and their growth depends on enterocytes arising from the crypt. Mature crypt cells are capable of digestion-absorptive activities and dominate the villus shortly after the chick hatches when yolk sac reserves are depleted. PMID- 2582105 TI - Monoclonal antibodies specific for subsets of epidermal keratins: biochemical and immunocytochemical characterization--applications in pathology and cell culture. AB - Keratin composition has been widely used as a biochemical marker of differentiation in normal epithelia, cell culture systems and tumours of epithelial tissues. We have been developing a model system for the study of human squamous epithelial cell differentiation, and among a panel of monoclonal antibodies we have generated for analysing this system are two antibodies recognizing subsets of epidermal keratins. The two antibodies, designated LICR LON-16a and LICR-LON-29b, were raised to the human squamous carcinoma cell line LICR-LON-HN-5, and we describe here their biochemical and immunocytochemical characterization. Antibody 16a reacts with only epidermal basal cells in normal human skin and shows specificity for the 45 and 46 kdalton keratins. Antibody 29b stains all living layers of the epidermis, and reacts with a broad range of ketain polypeptides, (45-56 kdaltons) in immunoblotting analyses. We have investigated the alterations of cellular staining that occur in chronic hyperproliferative skin diseases and carcinomas and compared this with the staining of multilayered cultures of normal keratinocytes and the HN-5 cell line. We show that in squamous cell carcinomas and in HN-5 cell xenografts 16a and 29b stain only the well-differentiated cell types. Furthermore we found that the basal cell specificity of 16a was lost in all of the hyperproliferative skin lesions examined including psoriasis and eczema. This transition to suprabasal staining pattern was also seen in the cultures of normal keratinocytes and HN-5 cells. We conclude that aberrant keratin synthesis or abnormal post-translational processing of keratins associated with an increased rate of cell turnover could account for the altered expression of the epitope recognized by antibody 16a. PMID- 2582106 TI - Clinical presentation of homozygous sickle cell disease. AB - The pattern of initial clinical symptoms and signs developing in a representative sample of 305 children with homozygous sickle cell (SS) disease diagnosed at birth was analyzed. Specific symptoms were present by age 6 months in 6% of the group, and had developed by the first to eighth birthdays in 32%, 61%, 78%, 86%, 90%, 92%, 94%, and 96%, respectively. Inclusion of nonspecific symptoms in the analysis led to earlier recognition by a mean of 3 months in the first year and by a mean of approximately 1 year between the ages of 2 and 4 years. Dactylitis was the most common initial symptom, noted in 40% of the group overall and in 50% in the first 2 years. Painful crisis was the first symptom in more than one fourth of the patients and was the most frequent symptom after the age of 2 years. Acute splenic sequestration led to presentation in one-fifth of the group overall and in one third of patients younger than 2 years. The most common nonspecific symptom was pneumonia. There was a significant trend of earlier presentation in children with low fetal hemoglobin levels. The age at presentation did not appear to be affected by alpha-thalassemia status. PMID- 2582107 TI - Treatment of acute idiopathic thrombocytopenia of childhood with intravenous infusions of gammaglobulin. AB - Gammaglobulin treatment was given at a dose of 1 gm/kg/day intravenously in 29 patients with acute idiopathic thrombocytopenic purpura: 15 previously untreated, 10 resistant to steroids, and four who were steroid dependent. The average platelet increase in 24 hours was greater than 50,000/microliter; the average peak platelet count was 194,000/microliter. Eighteen of 25 patients required only one infusion; 10 of these 18 never required any additional (maintenance) therapy. Outcome in previously untreated and steroid-resistant patients was identical; however, previously untreated patients required only 1.8 gm/kg total dose of gammaglobulin, whereas steroid-resistant patients received 3.9 gm/kg. Only one steroid-dependent child of the 29 patients still requires maintenance therapy, at 6-week intervals. Toxicity was minimal. Cost was minimized by not admitting patients and by giving treatment in one visit, rather than five. PMID- 2582108 TI - Value of methylene blue examination, dark-field microscopy, and carbol-fuchsin Gram stain in the detection of Campylobacter enteritis. PMID- 2582109 TI - Anxiety and dream symbolism. AB - The present study replicates and extends previous findings of a relation between anxiety level and the use of dream symbolism. Anxiety, assessed by self-reports over a ten-day period, was positively related to the use of sexual symbolism identified from dream reports obtained over the same period. The appearance of symbolic dreams, however, was not preceded by elevated levels of anxiety. A positive relation was uncovered between the measure of anxiety and a measure of manifest sexual content in the dreams. PMID- 2582110 TI - Ornithine decarboxylase inhibition and the malaria-infected red cell: a model for polyamine metabolism and growth. AB - The addition of DL-alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, to human Plasmodium falciparum-infected red cells in continuous culture decreased both parasite growth and intracellular polyamine concentrations. Growth of P. falciparum in infected red cells was assessed by parasite counts and by assays for macromolecular syntheses of protein, DNA and RNA. Polyamine concentrations were measured by an automated high-performance liquid chromatography method. Concentrations of DL-alpha-difluoromethylornithine greater than 0.3 mM decreased intracellular levels of putrescine and spermidine, reduced ornithine decarboxylase activity and inhibited growth and maturation of the intracellular parasite at the trophozoite stage. There was a concomitant decrease in the synthesis of protein and nucleic acids in the infected cells. The use of this parasitized red cell model system together with polyamine inhibitors provide means of studying polyamine synthesis and cell growth in the design of new antimalarial therapy. PMID- 2582111 TI - Cation activation of the pig kidney sodium pump: transmembrane allosteric effects of sodium. AB - We have studied activation by Na or Rb ions of different transport modes of the Na-K pump, using phospholipid vesicles reconstituted with pig kidney Na-K-ATPase. The shape of the activation curves, sigmoid or quasi-hyperbolic, depends on the nature of the cation at the opposite surface and not on the specific mode of transport. ATP-dependent Na uptake into K-containing vesicles (Na-K exchange) is activated by cytoplasmic Na along a highly sigmoid curve in the absence of extracellular Na (Hill number, nH = 1.9). Activation displays progressively less sigmoid curves as extracellular Na is raised to 150 mM (nH = 1.2). The maximal rate of the Na-K exchange is not affected. Na is not transported from the extracellular face by the pump in the presence of excess extracellular K, and the transmembrane effects of the extracellular Na are therefore 'allosteric' in nature. ATP-dependent Na-Na exchange (Lee & Blostein, 1980) and classical ATP plus-ADP-dependent Na-Na exchange are activated by cytoplasmic Na along hyperbolic curves. ATP-dependent Na uptake into Tris-containing vesicles is activated by cytoplasmic Na along a somewhat sigmoidal curve. (ATP + Pi) dependent Rb-Rb exchange is activated by cytoplasmic and extracellular Rb along strictly hyperbolic curves. The same applies for Rb-Rb exchange in the presence or absence of ATP or Pi alone. The presence of a high concentration of extracellular Na together with extracellular Rb induces a sigmoidal activation by cytoplasmic Rb of (ATP + Pi)-dependent Rb-Rb exchange (nH = 1.45) but does not affect the maximal rate of exchange. Slow passive Rb fluxes through the pump observed in the absence of other pump ligands (see Karlish & Stein, 1982 alpha) are activated by cytoplasmic Rb along a strictly hyperbolic curve with extracellular Rb, nH = 1.0 (Rb-Rb exchange), along a strongly sigmoid curve with extracellular Na, nH = 1.5 (Rb-Na exchange), and along less-sigmoid curves with extracellular Tris, nH = 1.24 (net Rb flux) or extracellular Li, nH = 1.2 (Rb-Li exchange). Activation of the passive Rb fluxes by extracellular Rb is hyperbolic in the presence of cytoplasmic Rb, Li or Tris but is sigmoid in the presence of cytoplasmic Na (nH = 1.36). Inhibition by cytoplasmic Na of passive Rb fluxes from the cytoplasmic to the extracellular face of the pump depends on the nature of the cation at the extracellular surface.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2582112 TI - Efflux of 5-hydroxytryptamine and noradrenaline into spinal cord superfusates during stimulation of the rat medulla. AB - High pressure liquid chromatography with electrochemical detection was used to quantify the efflux, in the same sample, of endogenous 5-hydroxytryptamine (5 HT), noradrenaline (NA), and 5-hydroxyindoleacetic acid (5-HIAA) into superfusates of the rat spinal cord in vivo. The efflux of these three agents was measured prior to, and during, electrical stimulation of the nucleus raphe magnus (n.r.m.) and nucleus reticularis paragigantocellularis (n.r.p.g.), two medullary nuclei implicated in antinociception. In untreated rats, basal efflux of 5-HT and NA was 0.21 and 0.12 ng/ml of superfusate respectively; the basal efflux of 5 HIAA was 18.17 ng/ml. Stimulation of the n.r.m. and n.r.p.g. in these animals increased the efflux of 5-HT and 5-HIAA, but did not alter the efflux of NA. 60 min after administration of fluoxetine (10 mg/kg, I.P.), a 5-HT uptake inhibitor, basal efflux of 5-HT and NA was unaltered, but the basal efflux of 5-HIAA was decreased. In these rats, stimulation of the n.r.m. and n.r.p.g. increased the efflux of 5-HT and of NA. The efflux of 5-HIAA was not altered. In rats pre treated with both fluoxetine and desipramine (10 mg/kg, I.P.), the basal efflux of NA was increased while that of 5-HIAA was decreased; the basal efflux of 5-HT was not affected. The efflux of NA, but not of 5-HT, was increased in these animals during stimulation of the n.r.m. and n.r.p.g. The efflux of 5-HIAA was not changed by stimulation. Addition of fluoxetine alone or with desipramine to the superfusate in high concentrations greatly increased basal efflux of 5-HT. Failure of stimulation of the ventromedial medulla to increase the efflux of 5-HT in these animals may be related to feed-back inhibition of release by the high concentration of 5-HT initially present in the superfusate. These results indicate that electrical stimulation of the n.r.m. and n.r.p.g. increases the efflux of endogenous 5-HT and NA from the spinal cord. These stimulation sites are coincident with brain-stem sites at which stimulation produces antinociception by activation of spinal serotonergic and noradrenergic receptors. Thus, the ability of stimulation at these sites to evoke the spinal release of the probable neurotransmitters further supports the hypothesis that the antinociceptive effect is mediated by activation of serotonergic and noradrenergic neurones projecting to the spinal cord. PMID- 2582113 TI - Mechano-electrical transduction currents in isolated vestibular hair cells of the chick. AB - Properties of a mechano-electrical transduction channel were studied in enzymatically dissociated chick vestibular hair cells by using a whole-cell recording variation of the patch voltage-clamp technique. The apical hair bundle was stimulated by a glass rod which moved along a one-dimensional axis when stimulated by either a triangular or a trapezoidal command voltage. The motion of the glass rod was monitored optically using a photodiode. In response to triangular stimuli, the hair cell generated a current of triangular wave form with occasional step-like spiky or zigzag-appearing events. Control experiments confirmed that the current was generated only when the hair bundle was displaced towards the tallest stereocilium. The mechano-sensitive current was blocked by streptomycin and by neomycin. The blockage by streptomycin was clearly voltage dependent: the reduction of the current became larger with hyperpolarization of the membrane. This suggests that the positively charged antibiotic molecules plug the mechanically gated channels. From the evidence presented in 3 and 4 above, the mechano-sensitive current recorded here was identified as the mechano electrical transduction (m-e.t.) current. The permeability of the m-e.t. channel to various monovalent cations was determined from reversal potential measurements. Since a CsCl-EGTA intracellular medium was used, all the permeabilities were calculated relative to PCs. The sequence of permeabilities was Li greater than Na greater than or equal to K greater than or equal to Rb greater than Cs greater than choline greater than TMA greater than TEA. External Ca ions were indispensable for the recording of transduction current and Sr ions could replace Ca ions without loss of the transduction activity. The minimum [Ca]o for stable generation of the m-e.t. current was 20 microM in Cs saline. The addition of 50-200 microM-Ca to the isotonic Ba saline could maintain the m-e.t. current. The m-e.t. current was observed in isotonic Ca and in Sr salines. Isotonic Ba, Mg and Mn salines were enriched with 1-2 mM-Ca in order to generate the m-e.t. current. The permeabilities of the divalent cations relative to Cs were calculated from the reversal potentials, and the sequence of permeabilities among divalent cations was Ca greater than Sr greater than Ba greater than Mn greater than Mg. Step-like m-e.t. currents were observed in Cs saline. The smallest step amplitude with clear resolution had a conductance of 49.7 +/- 4.5 pS (mean +/- S.D., n = 7 cells). This is likely to be an elementary m-e.t. channel conductance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2582114 TI - Electrogenic active proton pump in Rana esculenta skin and its role in sodium ion transport. AB - Kinetic and electrophysiological studies were carried out in the in vitro Rana esculenta skin, bathed in dilute sodium solution, to characterize the proton pump and coupling between sodium absorption (JNa+n) and proton excretion (JH+n). JNa+n and JH+n were both dependent on transepithelial potential (psi ms); hyperpolarizing the skin decreased JNa+n and increased JH+n; depolarization produced the opposite effects. Amiloride (5 X 10(-5) M) at a clamped psi ms of +50 mV inhibited JNa+n without affecting JH+n. Variations of psi ms or pH had identical effects on JH+n. Ethoxzolamide inhibited JH+n and simultaneously increased psi ms by 15-30 mV. These changes were accompanied by depolarization of the apical membrane potential psi mc from -47 to -25 mV and an increase in apical membrane resistance of 30%; no significant effects on basolateral membrane potential (psi cs) and resistance (Rb) nor on shunt resistance (Rj) were observed. The proton pump appears to be localized at the apical membrane. The proton pump was also inhibited by deoxygenation, oligomycin, dicyclohexylcarbodiimide and vanadate (100, 78, 83 and 100% inhibition respectively). The variations of JH+n and of the measured electrical currents were significantly correlated. These findings are supportive evidence of a primary active proton pump, electrogenic and strictly linked to aerobic metabolism. The current-voltage (I-V) relation of the proton pump was obtained as the difference in the I-V curves of the apical membrane extracted before and after proton-pump inhibition by ethoxzolamide during amiloride block of sodium transport. The proton-pump current (IP) was best described by a saturable exponential function of psi mc. Maximal pump current (ImaxP) was calculated to be 200 nequiv h-1 cm-2 at a psi mc of +50 mV and the pump reversal potential ERP was -130 mV. The effect of ethoxzolamide to depolarize psi mc was dependent on the relation between psi mc and ERP. Maximal induced depolarization occurred at a psi mc of +50 mV whereas ethoxzolamide exerted minimal effect on psi mc when the ERP was approached either by voltage clamping the apical membrane or by the addition of amiloride. We show that electroneutral sodium-proton countertransport is not the mechanism of active proton excretion in frog skin but that it is the proton excretion which provides a favourable electrical driving force for passive apical sodium entry.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2582115 TI - Two types of calcium channels in the somatic membrane of new-born rat dorsal root ganglion neurones. AB - Ca2+ inward currents evoked by membrane depolarization have been studied by the intracellular dialysis technique in the somatic membrane of isolated dorsal root ganglion neurones of new-born rats. In about 20% of the investigated cells a hump has been detected on the descending branch of the current-voltage curve, indicating the presence of two populations of Ca2+ channels differing in their potential-dependent characteristics. An initial less regular component of the Ca2+ current was activated at membrane potentials from -75 to -70 mV. Its amplitude reached 0.2-0.9 nA at 14.6 mM-extracellular Ca2+. The activation kinetics of this component could be approximated by the Hodgkin-Huxley equation using the square of the m variable. tau m varied in the range from 8 to 1 ms at potentials between -60 and -25 mV ('fast' Ca2+ current). The second component of the Ca2+ current was activated at membrane depolarizations to between -55 and -50 mV. It could be recorded in all cells investigated and reached a maximum value of 1-7 nA at the same extracellular Ca2+ concentration. This component decreased rapidly during cell dialysis with saline solutions. The decrease could be slowed down by cooling and accelerated by warming the extracellular solution. Intracellular introduction of 3',5'-cAMP together with ATP and Mg2+ not only prevented the decrease but often restored the maximal current amplitude to its initial level. The activation kinetics of this component could also be approximated by a square function, tau m being in the range 16-2.5 ms at membrane potentials between -20 and +3 mV ('slow' Ca2+ current). The fast Ca2+ current inactivated exponentially at sustained depolarizations in a potential-dependent manner, tau h varying from 76 to 35 ms at potentials between -50 and -30 mV. The inactivation of the slow Ca2+ current studied in double-pulse experiments was current-dependent and developed very slowly (time constant of several hundreds of milliseconds). It slowed down even more at low temperature or after substitution of Ba2+ for Ca2+ in the extracellular solution. Both currents could also be carried by Ba2+ and Sr2+, although the ion-selecting properties of the two types of channels showed quantitative differences. Specific blockers of Ca2+ channels (Co2+, Mn2+, Cd2+, Ni2+ or verapamil) exerted similar effects on them. The existence of metabolically dependent and metabolically independent Ca2+ channels in the neuronal membrane and their possible functional role are discussed. PMID- 2582116 TI - Membrane currents and their modification by acetylcholine in isolated single atrial cells of the guinea-pig. AB - The ionic currents in isolated single atrial cells of the guinea-pig heart were analysed by the patch-clamp technique applied to whole-cell recordings and the effects of acetylcholine (ACh) on the membrane potential and currents were studied. Resting and action potentials of single isolated cells were normal. Upstroke velocity was sensitive to tetrodotoxin. Action potential duration was slightly shorter than in multicellular preparations. Voltage-clamp experiments demonstrated the presence of a Ca2+ current (iCa), and inward rectifying and outward rectifying K+ currents. The Ca2+ current was abolished by 2 mM-Co2+ or 10(-6) M-D600, and the K+ currents were greatly reduced by intracellular application of Cs+ using the patch electrode and simultaneously superfusing the cell with 5 mM-Cs+ Tyrode solution. Acetylcholine shortened the action potential duration in a dose-dependent manner. The threshold dose of ACh was about 10(-9) M and the maximal effect was obtained with 10(-6) M. The resting membrane potential was hyperpolarized by 1-3 mV. ACh (10(-8)-10(-6) M) increased the K+ currents both on depolarization and on hyperpolarization in a dose-dependent manner in the presence of 10(-6) M-D600. The ACh-induced K+ outward current revealed a progressive deactivation ('relaxation'), with a time constant of 111 +/- 16 ms at around 0 mV. When the K+ outward currents were minimized with Cs+, the reduction of iCa by 10(-8) M-ACh was insignificant, and became 17 +/- 2.5, 26 +/- 3.5 and 26 +/- 5% of the control value in 10(-7), 10(-6) and 10(-5) M-ACh, respectively. The inactivation time course of iCa recorded from the Cs+-loaded cells was not affected by 10(-7) M-ACh. These results suggest that ACh activates predominantly a K+ conductance in the guinea-pig atrium. The superimposition of a relaxing K+ outward current on iCa may lead to over-estimation of the decrease in iCa. PMID- 2582117 TI - A comparison of digital and optical criteria for detecting carious dentin. PMID- 2582118 TI - Tumour markers in testicular cancer. PMID- 2582119 TI - Chemotherapy for non-seminomatous germ-cell tumours. PMID- 2582121 TI - High-conductance K+ channel in pancreatic islet cells can be activated and inactivated by internal calcium. AB - The Ca2+-activated K+ channel in rat pancreatic islet cells has been studied using patch-clamp single-channel current recording in excised inside-out and outside-out membrane patches. In membrane patches exposed to quasi-physiological cation gradients (Na+ outside, K+ inside) large outward current steps were observed when the membrane was depolarized. The single-channel current voltage (I/V) relationship showed outward rectification and the null potential was more negative than -40 mV. In symmetrical K+-rich solutions the single-channel I/V relationship was linear, the null potential was 0 mV and the single-channel conductance was about 250 pS. Membrane depolarization evoked channel opening also when the inside of the membrane was exposed to a Ca2+-free solution containing 2mM EGTA, but large positive membrane potentials (70 to 80 mV) were required in order to obtain open-state probabilities (P) above 0.1. Raising the free Ca2+ concentration in contact with the membrane inside ( [Ca2+]i) to 1.5 X 10(-7) M had little effect on the relationship between membrane potential and P. When [Ca2+]i was increased to 3 X 10(-7) M and 6 X 10(-7) M smaller potential changes were required to open the channels. Increasing [Ca2+]i further to 8 X 10(-7) M again activated the channels, but the relationship between membrane potential and P was complex. Changing the membrane potential from -50 mV to +20 mV increased P from near 0 to 0.6 but further polarization to +50 mV decreased P to about 0.2. The pattern of voltage activation and inactivation was even more pronounced at [Ca2+]i = 1 and 2 microM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582120 TI - Advances in pathology and immunocytochemistry. PMID- 2582122 TI - Permeability of the squid giant axon to organic cations and small nonelectrolytes. AB - The permeability of the Na channel of squid giant axon to organic cations and small nonelectrolytes was studied. The compounds tested were guanidinium, formamidinium, and 14C-labeled urea, formamide, thiourea, and acetone. Permeability was calculated from measurements of reversal potential and influx on internally perfused, voltage clamped squid axons. The project had two objectives: (1) to determine whether different methods of measuring the permeability of organic cations yield similar values and (2) to see whether neutral analogs of the organic cations can permeate the Na channel. Our results show that the permeability ratio of sodium to a test ion depends upon the ionic composition of the solution used. This finding is consistent with the view put forward previously that the Na channel can contain more than one ion at a time. In addition, we found that the uncharged analogs of permeant cations are not measurably permeant through the Na channel, but instead probably pass through the lipid bilayer. PMID- 2582123 TI - Comparison of time constants of single channel patches, quantum bumps, and noise analysis in Limulus ventral photoreceptors. AB - The characteristic time constants derived from three different experimental procedures for measuring light-evoked currents in photoreceptors are compared; these procedures include single-channel patch-clamp measurements, noise analysis, and current relaxation studies. Recent patch-clamp measurements of the mean open times of single light-activated channels in the ventral photoreceptor of Limulus (Bacigalupo, J., Lisman, J.E. (1983), Nature (London) 304:268-270) yield a disagreement of the measured mean open time with the relaxation time of the falling phase of quantum bumps and with the inverse characteristic frequency of the noise power spectrum, measured by Wong (Wong, F. (1978), Nature (London) 276:76-79). We present new experimental results which show that the relaxation time of the falling phase of bumps is markedly shortened by light-adaptation. Hence the state of light-adaptation has to be taken into account when comparing different experiments. Secondly, we investigate three simple models for the mechanism of channel opening and closing, and conclude that an agreement of the mean open time of single channels, the relaxation time of the falling phase of bumps, and the inverse characteristic frequency of the noise power spectrum cannot be expected. PMID- 2582124 TI - Structure-activity relationship of amiloride analogs as blockers of epithelial Na channels: I. Pyrazine-ring modifications. AB - The overall on- and off-rate constants for blocking epithelial Na channels by amiloride analogs were estimated by noise analysis of frog skin epithelium. The substituents at position-5 and -6 of the pyrazine ring of amiloride were varied in order to obtain the structure/rate constant relationship. (1) The off-rate constant increases with halo-substitutions at position-6 in the order Cl less than Br less than l less than F less than H. Substitution of Cl by H lowers the standard free energy of activation of the off-step by 2.3 kcal mol-1. The on-rate constant is not affected. Apparently the substituent at ring position-6 controls the duration of attachment in the blocking position. pKa considerations show that the duration is longer when the 6-substituent is more negatively polarized. We suggest that this substituent binds to the receptor by virtue of its electronegativity. (2) In contrast, replacement of the adjacent 5-amino group (electron donor) by H or Cl affects both the on-rate and the off-rate. The dual effect may be explained by a decrease of the electronic charge at more remote parts of the molecule (on-rate decrease), as well as at the 6-position (off-rate increase). Apparently the 5-amino group stabilizes the blocking position by increasing the electron density on the 6-ligand. PMID- 2582125 TI - Voltage dependence and ion selectivity of the mitochondrial channel, VDAC, are modified by succinic anhydride. AB - The mitochondrial protein VDAC forms voltage-dependent anion-selective channels in planar phospholipid membranes. When succinic anhydride was added to these membranes, it virtually eliminated VDAC's voltage-dependence and changed its selectivity from anion to cation. These results were obtained without large changes in open-channel conductance or in energy difference between the open and closed states in the absence of a field. Since succinic anhydride converts amino groups into carboxyl groups, we propose that amino groups are responsible for VDAC's voltage-dependence and anion selectivity. Perhaps the same charges are responsible for both functions. PMID- 2582126 TI - The mitochondrial voltage-dependent channel, VDAC, is modified asymmetrically by succinic anhydride. AB - In the accompanying paper, succinic anhydride was shown to react with the outer mitochondrial membrane channel-forming protein, VDAC, resulting in the loss of its voltage dependence. In this paper, the anhydride was added to VDAC held in a particular conformational state by means of an applied electric field. VDAC was inserted into the membranes from the cis side and the anhydride was added either to the cis or trans side. Channels modified in the open state behaved similarly whether anhydride was added to the cis or trans side. Modifications of VDAC in either of the two closed states did not. Modifications resulting in the loss of voltage-dependence occurred primarily when anhydride was added to the negative side of the membrane irrespective of which closed state the VDAC was in indicating that the accessibility of the gating charges alternated between the cis and trans sides as the channel's conformation was changed from one closed state to the other. Despite the pronounced asymmetry, in general the resulting channels behaved in the same way in response to either positive or negative fields. A model consistent with the results is presented which proposes that the same gating charges are responsible for channel closure at both positive and negative fields. PMID- 2582127 TI - K+ and Cl- conductances in the apical membrane from secreting oxyntic cells are concurrently inhibited by divalent cations. AB - This study concerns the properties of rapid K+ and Cl transport pathways that are present in the (H+ + K+)-ATPase membrane from stimulated, and secreting, gastric oxyntic cells. Ion permeabilities in the isolated stimulation-associated vesicles were monitored via the rates of H+ efflux under conditions of exclusive H+/K+ counterflux or H+ - Cl co-efflux, as well as by comparison of equilibration rates for 86Rb and 36Cl under conditions of equilibrium exchange and unidirectional salt flux. These latter studies suggest that Rb+ and Cl pathways are conductive and independent. In spite of the functional independence of the ion pathways, several divalent cations inhibit Rb+ and Cl isotopic exchange as well as the H+ efflux that is dependent on either K+ or anion (Cl, SCN, NO2) fluxes. Zn2+ is the more potent inhibitor, reducing by 50% the sensitive component of K+, Cl, and NO2 fluxes at about 20 microM; Mn2+ has a similar effect at 200 microM. Ni2+ and Co2+ were roughly equipotent to Mn2+ while Mg2+ and Ca2+ had no inhibitory effect. These results suggest that the stimulation-induced permeabilities, while functioning independently, may be physically linked, i.e., residing within a single entity. In similar studies carried out in (H+ + K+)-ATPase vesicles obtained from nonstimulated cells, no vestiges of sensitivity to the inhibitory divalent cations could be detected. The implications of these findings for the physiology of the oxyntic cell in the context of a model for membrane fusion are discussed. PMID- 2582129 TI - Experimental and theoretical studies on Tl+ interactions with the cation selective channel of the sarcoplasmic reticulum. AB - This paper presents an experimental study and a theoretical interpretation of the effects of thallous ion on the electrical properties of the cation-selective channel of the sarcoplasmic reticulum (SR channel). The properties of this channel in solutions which do not contain thallous ion are consistent with the predictions of Lauger's theory for singly occupied pores (P. Luger, 1973, Biochim. Biophys. Acta 311:423-441). However, this theory does not account for SR channel properties in mixtures containing thallous ion. SR channel conductance is less than predicted in mixed salt solutions of thallium with either potassium or ammonium (J. Fox, 1983, Biochim. Biophys. Acta 736:241-245), yet is greater than expected in mixtures of lithium and thallium. In a simple single-ion pore, the ratio of the products of the single-salt binding constants and maximum conductances is equal to the permeability ratio calculated from zero-current potential experiments under near equilibrium conditions. This is not found for the SR channel when thallous ion is present. SR channel properties in the presence of thallous ion can, however, be explained by a model which postulates the existence of two external modulatory sites on the channel, without implying double-occupancy in the permeation pathway. When thallous ion is bound to a modulatory site the maximum conductance of the channel to all permeating ions is altered (thallous included). Two other models (a three-barrier, two-internal-site pore which allows multiple occupancy, and a pore with fluctuating barriers) are discussed, but are found to be unable to fit our conductance data at different concentrations. PMID- 2582128 TI - Effect of phospholipid surface charge on the conductance and gating of a Ca2+ activated K+ channel in planar lipid bilayers. AB - A Ca-activated, K-selective channel from plasma membrane of rat skeletal muscle was studied in artificial lipid bilayers formed from either phosphatidylethanolamine (PE) or phosphatidylserine (PS). In PE, the single channel conductance exhibited a complex dependence on symmetrical K+ concentration that could not be described by simple Michaelis-Menten saturation. At low K+ concentrations the channel conductance was higher in PS membranes, but approached the same conductance observed in PE above 0.4 m KCl. At the same Ca2+ concentration and voltage, the probability of channel opening was significantly greater in PS than PE. The differences in the conduction and gating, observed in the two lipids, can be explained by the negative surface charge of PS compared to the neutral PE membrane. Model calculations of the expected concentrations of K+ and Ca2+ at various distances from a PS membrane surface, using Gouy-Chapman Stern theory, suggest that the K+-conduction and Ca2+-activation sites sense a similar fraction of the surface potential, equivalent to the local electrostatic potential at a distance of 9 A from the surface. PMID- 2582130 TI - Monovalent cation permeabilities of the potassium systems in the crab giant axon. AB - Permeability ratios for pairs of monovalent cations permeating the two potassium systems proposed for the giant axon of the crab Carcinus maenas (M.E. Quinta Ferreira, E. Rojas & N. Arispe, J. Membrane Biol. 66:171-181, 1982b) were estimated from measurements of the reversal potential of the currents under voltage-clamp conditions. With K+ inside the axon, permeability ratios from the reversal potential of the currents through the late channel are: PRb/PK = 0.9, PNH4/PK less than 0.2 and PCS/PK = 0.18. With CS+ inside the ratios are: PK/PCS = 8.7, PRb/PCS = 7.1 and PNH4/PCS = 2.4. The analysis of the inward currents carried by Rb+ or NH+4 showed similar reversal potentials for the early transient component and the late sustained component. Whence, the sequence of permeabilities for the two types of potassium channels is: PK greater than PRb greater than PNH4 greater than PNa = PCS. The time constants for the activation of the two components recorded either in K-, Rb-, or NH4-artificial seawater are twice as large as the corresponding time constants measured in Na-artificial seawater. PMID- 2582132 TI - Transport of hydrophobic ions in erythrocyte membrane: I. Zero membrane potential properties. AB - The permeability and partition coefficients of tetraphenylarsonium (TPA) and several other organic cations were studied in the human erythrocyte using an ion selective electrode. The permeability constant for the different cations could be explained quite well by differences in oil/water partition coefficients. No evidence for facilitated transport could be found. Binding of the organic ions occurred to both the cell membrane and to intracellular contents. Partitioning to the membrane remained relatively constant despite variation from ion intracellular binding with blood samples from different donors. TPA flux is stimulated by substoichiometric amounts of tetraphenylboron and other organic anions, suggesting an ion-pairing mechanism. PMID- 2582131 TI - Differential blockage of two types of potassium channels in the crab giant axon. AB - Measurements were made of the kinetic and steady-state characteristics of the potassium conductance in the giant axon of the crabs Carcinus maenas and Cancer pagirus. The conductance increase during depolarizing voltage-clamp pulses was analyzed assuming that two separate types of potassium channels exist in these axons (M.E. Quinta-Ferreira, E. Rojas and N. Arispe, J. Membrane Biol. 66:171 181, 1982). It is shown here that, with small concentrations of conventional K+ channel blockers, it is possible to differentially inhibit these channels. The potassium channels with activation and fast inactivation gating (m3h, Hodgkin Huxley kinetics) were blocked by external application of 4 amino-pyridine (4-AP). The potassium channels with standard gating (n4, Hodgkin-Huxley kinetics) were preferentially inhibited by externally applied tetraethylammonium (TEA). The differential blockage of the two types of potassium conductance changes suggests that they represent two different populations of potassium channels. It is further shown here that blocking the early transient conductance increase leads to the inhibition of the repetitive electrical activity induced by constant depolarizing current injection in fibers from Cardisoma guanhumi. PMID- 2582133 TI - Channels formed by colicin E1 in planar lipid bilayers are large and exhibit pH dependent ion selectivity. AB - The E1 subgroup (E1, A, Ib, etc.) of antibacterial toxins called colicins are known to form voltage-dependent channels in planar lipid bilayers. The genes for colicins E1, A and Ib have been cloned and sequenced, making these channels interesting models for the widespread phenomenon of voltage dependence in cellular channels. In this paper we investigate ion selectivity and channel size- properties relevant to model building. Our major finding is that the colicin E1 channel is large, having a diameter of at least 8 A at its narrowest point. We established this from measurements of reversal potentials for gradients formed by salts of large cations or large anions. In so doing, we exploited the fact that the colicin channel is permeable to both cations and anions, and its relative selectivity to them is a function of pH. The channel is anion selective (Cl- over K+) in neutral membranes, and the degree of selectivity is highly dependent on pH. In negatively charged membranes, it becomes cation selective at pH's higher than about 5. Experiments with pH gradients cross the membrane suggest that titratable groups both within the channel lumen and near the channel ends affect the selectivity. Individual E1 channels have more than one open conductance state, all displaying comparable ion selectivity. Colicins A and Ib also exhibit pH-dependent ion selectivity, and appear to have even larger lumens than E1. PMID- 2582134 TI - A modification of the chronic tartrate silver impregnation technique for block impregnation of the central nervous system and paraffin wax embedding. AB - This paper describes a block silver impregnation technique for the CNS. The procedure, which is quite simple, yields highly consistent and reproducible results. After fixation during 6-10 days in 10% saline formaldehyde, 4 mm thick blocks of brain are treated with chromic anhydride and sodium potassium tartrate solution for 4 days. After this period the specimens are rinsed in 0.75% silver nitrate solution to which 8-10 drops of pyridine per 100 ml of solution have been added. This is followed by impregnation for 4 days at 37 degrees C in silver nitrate-pyridine solution identical to that used in the previous rinsing step. The impregnated blocks are reduced during 20-26 h in 1% pyrogallol to which 6 ml commercial formaldehyde per 100 ml of solution have been added, followed by dehydration in dioxan and paraffin embedding. Sections no thicker than 30 microns are then cut for histological study. This fundamentally neurofibrillar method reveals: neuronal somata and their processes; synaptic structures; fibre bundles; and cell nuclei and nucleoli. PMID- 2582135 TI - Activation and inhibition of transcription by supercoiling. AB - Stimulation of transcriptional activity in vitro is observed at low and moderate negative superhelical densities up to the level of the natural superhelical form of the plasmid pBR322. We have isolated and identified three specific transcription products: ampicillinR RNA, tetracyclineR RNA and "Rep" RNA. Their enhancement of transcription occurs at different levels of superhelicity, suggesting a sequence-dependent structural alteration of promoters upon changes of axial writhe, which may generate kink formation. The activation of transcription is drastically inhibited at higher specific linking differences exceeding that of the natural superhelical form of pBR322, which is correlated with a transition from the right-handed B to a left-handed DNA form of particular sequences induced by supercoiling. We have identified a new stop point in the beta-lactamase coding sequence composed of eight alternating purine-pyrimidine residues which, at higher torsional stress, causes transcription to stop, leading to the synthesis of a short RNA of about 55 nucleotides instead of AmpR RNA (about 580 nucleotides). In the "Rep" promoter, two alternating purine-pyrimidine segments are found, which conformational change at higher superhelical densities may be implicated in repression of "Rep" RNA synthesis. The enhancement and inhibition of transcription by supercoiling support the role of energetic and structural changes in topologically constrained DNA as elements of a control mechanism. PMID- 2582136 TI - Effect of spermidine on the conformation of bacteriophage MS2 RNA. Electron microscopy and computer modeling. AB - The structure of single-stranded RNA from the bacteriophage MS2 has been examined by electron microscopy in the presence of the polyamine spermidine. The molecules are found in two alternate conformations. The first of these can be characterized as a cruciform structure composed of three large loops approximately 500 to 700 nucleotides in size. The interior of the molecule has extensive base-paired regions which connect distant regions of the molecule; the farthest being 2500 nucleotides apart. In the second conformation, the molecules appear rod-like. Two of the large loops disappear, and these regions form, instead, extensive long range helices. Computer modeling has been employed to explore the base-pairing potential of the sequence of bacteriophage MS2 RNA. Double-stranded regions identified by electron microscopy are shown to occur in local G + C-rich stretches of the RNA. Detailed models have been calculated for two regions of long-range contact. One of these includes the ribosome-binding site for the viral coat protein gene. The results are discussed in the context of the known role of RNA structure in the regulation of viral gene expression. PMID- 2582138 TI - Extrachromosomal DNA forms of copia-like transposable elements, F elements and middle repetitive DNA sequences in Drosophila melanogaster. Variation in cultured cells and embryos. AB - Drosophila melanogaster embryos and cells in culture were screened for the presence of unintegrated covalently closed circular DNA forms that hybridize to copia-like transposable elements, the F element and uncharacterized dispersed middle repetitive DNA elements. Our results indicate that the majority of copia like elements (including copia, 297, 412, mdg1, mdg3 and gypsy), the F elements, and 9 of 12 middle repetitive DNA elements are present as free DNA forms in cultured cells and embryos. An 18 base-pair inverted repeat has been reported to flank the long direct repeat of mdg3, implying that mdg3 is not an orthodox copia like element; however, we have sequenced two independently isolated mdg3 clones and shown that the inverted repeat is not part of the element. The relative abundance with which free DNA forms are found varies between the cultured cells used, and between cultured cells and embryos. This variation, which can be up to 20-fold for some elements, does not correlate well with either the amount of element-specific poly(A)+ RNA present per cell or the number of element-specific sequences integrated in the genome. PMID- 2582137 TI - Nucleosome disruption precedes transcription and is largely limited to the transcribed domain of globin genes in murine erythroleukemia cells. AB - We used micrococcal nuclease to separate murine erythroleukemia cell (MELC) chromatin into soluble and insoluble fractions which differ in gene content and chromatin structure. Genes that are not expressed in the erythroid lineage, such as the Ig alpha and albumin genes, distribute preferentially into the soluble rather than the insoluble fraction, and are organized into nucleosomes in both fractions. Both alpha 1- and beta maj-globin genes are enriched in the insoluble fraction and are organized into structures that are partially devoid of nucleosomes in uninduced MELC, when the genes are transcriptionally inactive. Following chemical induction of MELC and the onset of globin gene transcription, globin gene enrichment and nucleosome disruption in the insoluble chromatin fraction increase. Using seven DNA subclones that span the beta maj-globin gene we show that insolubility and nucleosome disruption are largely limited to DNA sequences lying within the transcribed domain. Non-transcribed, flanking sequences are soluble and organized into nucleosomes. In addition, the globin genes found in insoluble, non-nucleosomal chromatin contain previously engaged RNA polymerases which can elongate globin RNA chains in vitro in a pattern qualitatively and quantitatively similar to intact nuclei. These results are discussed in terms of a model for globin gene activation during erythropoeisis. PMID- 2582139 TI - A mutation in an Escherichia coli ribosomal RNA operon that blocks the production of precursor 23 S ribosomal RNA by RNase III in vivo and in vitro. AB - We have isolated on a multicopy plasmid a mutant rrnB ribosomal RNA operon containing a 130 base-pair deletion immediately preceding the 23 S rRNA gene. The deletion shortens by just three base-pairs the 26 base-pair complementarity of the sequences that flank the 23 S rRNA gene, and which normally form an RNase III cleavage site in the rrnB primary transcript. Both in vivo and in vitro, cleavage at the altered RNase III site was almost completely abolished by the mutation. Our results therefore indicate that even a small perturbation of the double stranded region normally recognized by RNase III strongly inhibits the action of the enzyme. PMID- 2582141 TI - An evaluation of the combined use of nuclear magnetic resonance and distance geometry for the determination of protein conformations in solution. AB - An evaluation of the potential of nuclear magnetic resonance (n.m.r.) as a means of determining polypeptide conformation in solution is performed with the aid of a new distance geometry program which is capable of computing complete spatial structures for small proteins from n.m.r. data. Ten sets of geometric constraints which simulate the results available from n.m.r. experiments of varying precision and completeness were extracted from the crystal structure of the basic pancreatic trypsin inhibitor, and conformers consistent with these constraints were computed. Comparison of these computed structures with each other and with the original crystal structure shows that it is possible to determine the global conformation of a polypeptide chain from the distance constraints which are available from n.m.r. experiments. The results obtained with the different data sets also provide a standard by which the quality of protein structures computed from n.m.r. data can be evaluated when no crystal structure is available, and indicate directions in which n.m.r. experiments for protein structure determination could be further improved. PMID- 2582140 TI - The 5' ends of Escherichia coli lac mRNA. AB - We identified the predominant 5' ends of an mRNA in Escherichia coli to the exact nucleotides. There are four such ends of lac mRNA in fully induced cells. About 70% of the molecules have the reported major in vitro end, A-A-U-U-G (at +1), which is located 38 nucleotides before the A-U-G translation start. Another 15% start with A-U-U-G at +2, and about 8% start with A-U-U-A-G at -52. A fourth class of molecules begin with either A-G, C-A-G, A-C-A-G, or a weak A-C-A-C-A-G (at +24), observed only once. The origins of this latter set (less than or equal to 10% of the total) are not known, but they could represent "ragged" ends of the mRNA when it is degraded to the beginning of the ribosome-protected region of the message. The A-U-U-A-G molecules are probably initiated from an upstream promoter whose position would coincide with the cAMP-CRP DNA binding site for the major promoter. PMID- 2582142 TI - Good nursing care wards off disaster. PMID- 2582144 TI - High voltage electron microscopy of sperm axoneme. AB - The axoneme of sea urchin spermatozoon has been examined in whole preparation by high voltage electron microscopy. Radial spokes appear arranged in triplets with intratriplet distance of 40 nm, distance between spoke 1 and 2 of 32 nm and between spoke 2 and 3 of 24 nm. Spoke 1 is thicker than others; the complex of the triplets around the 9 microtubule doublets forms a helix of 96 nm pitch. Nexin links connect the A tubule of a doublet with the B of the adjacent one, and also form a helix of 96 nm pitch. PMID- 2582143 TI - Analysis of peritoneal lavage parameters in blunt abdominal trauma. AB - Peritoneal lavage is the most valuable diagnostic modality presently available for the evaluation of patients with blunt abdominal trauma. A retrospective review of 523 patients who underwent open peritoneal lavage for blunt abdominal trauma over a 3 1/2-year period revealed serious intra-abdominal pathology in 83% of patients undergoing laparotomy with RBC lavage counts in the range of 20,000 to 100,000 cells/mm3, a level considered by many authors to be negative or indeterminate. Two patients with isolated small bowel perforations had an elevated amylase level as the only measured abnormality. The data indicate that the standard guidelines for RBC positivity (positive count greater than 100,000 cells/mm3 and indeterminate count 50,000 to 100,000 cells/mm3) result in missed intraperitoneal injuries in a large percentage of patients and therefore require reevaluation. Lavage amylase determinations, previously stated to be costly and of insignificant yield, should be performed on patients whose lavage would otherwise be considered negative by RBC and WBC counts. PMID- 2582145 TI - Fine structure and cytochemistry of Phytomonas davidi. AB - The fine structure of Phytomonas davidi grown in an axenic medium was analyzed. The results obtained confirm a previous study and add new information. A large membrane-bounded cavity containing vesicles was observed near the nucleus. A vacuole was seen near the flagellar pocket. Its aspect varied from cell to cell and in some cells it was connected to a system of tubules and vesicles and may represent a contractile vacuole. In cells incubated in the presence of 0.1% Triton X-100 and then fixed in a glutaraldehyde solution containing tannic acid, a better visualization of filamentous structures was obtained than with conventional fixation. Filaments connecting the sub-pellicular microtubules to each other and to the plasma membrane were observed. Thin filaments were seen in the cytoplasm, mainly near the basal body. Imidazole-buffered osmium tetroxide solution was used to visualize lipids. Reaction product was seen in the matrix of the peroxisome-like (glycosome) organelle. A high contrast of the membranes which surround the nucleus and the mitochondrion was observed. Other membranes showed the usual aspect. PMID- 2582146 TI - Structure and possible functional role of septate junctions in the ovotestis of a pond snail: inter-Sertoli junctions. AB - Junctions between Sertoli cells, which form a continuous layer at the periphery of the 'acinus' in the ovotestis of Biomphalaria glabrata (mollusc gastropod), have been studied with conventional sections, lanthanum impregnation, replicas and scanning analysis of unstained sections. Extensive undulating septate junctions link Sertoli cells, which surround the various stages of spermatid differentiation. The morphology of the pleated septate junctions here presented indicates a possible role as a permeability barrier, which might result from the peculiar organization of the septa. The junctional complex is formed of areas where septa are parallel and regularly spaced, alternating with areas where septa separate and assemble with others, thus creating a complex system of channels, completely compatible with the sealing properties expected for these junctions. The morphology of septa, their possible anchorage within the membranes, and the interconnections linking the closely parallel septa are presented. PMID- 2582147 TI - Rotavirus neutralizing protein VP7: antigenic determinants investigated by sequence analysis and peptide synthesis. AB - The rotavirus neutralizing antigen, VP7, is a 37,000-molecular-weight glycoprotein which is a major component of the outer shell of the virion. The amino acid sequence of VP7 for strain S2 (human serotype 2) and Nebraska calf diarrhea virus (bovine serotype) has been inferred from the nucleic acid sequence of cloned copies of genomic segment nine. Comparison of the amino acid sequences of these two VP7 proteins with those already determined for other rotavirus strains reveals extensive sequence conservation between serotypes with clusters of amino acid differences sited predominantly in hydrophilic domains of the protein. Six peptides have been synthesized that span the hydrophilic regions of the molecule. Antisera to these peptides both recognize the respective homologous peptides in a solid-phase radioimmunoassay and bind to denatured VP7 in a Western blot. However, none of the antisera either recognize virus or exhibit significant neutralizing activity, indicating that these peptide sequences are not available on the surface of the virus. PMID- 2582148 TI - Regulation of Moloney murine leukemia virus replication in chronically infected cells arrested at the G0/G1 phase. AB - The replication of Moloney murine leukemia virus (MMuLV) in chronically infected mouse cells arrested at the G0/G1 phase of the cell cycle by different procedures was investigated. MMuLV production was inhibited in glutamine- and isoleucine (Gln-Ile)-deprived G0/G1 cells. In contrast, butyric acid treatment, which efficiently arrested the cells at the G0/G1 phase of the cell cycle, did not inhibit MMuLV production. Furthermore, the inhibition of MMuLV production caused by either Gln-Ile deprivation or by interferon (IFN) treatment was overcome by butyric acid treatment. Thus, the replication of MMuLV could be dissociated from cell proliferation. The inhibition of MMuLV production in Gln-Ile-deprived cell cultures was compared to the inhibitory effect of IFN, which is known to affect budding and release of the virus. Rates of MMuLV protein synthesis were not affected in both the IFN-treated and Gln-Ile-deprived cells. However, processing of the viral polyprotein Pre65gag into p30 was blocked in the Gln-Ile-deprived cells. Furthermore, whereas in IFN-treated cells, MMuLV accumulated on the cell surface and could be released upon treatment with trypsin, in Gln-Ile-deprived cells, no virions were released by such treatment. These results indicate that in cells arrested by Gln-Ile deprivation, MMuLV is inhibited at a posttranslation step. This step appears to precede the anti-MMuLV block induced by IFN. PMID- 2582149 TI - Competitive inhibition by human sera of mouse monoclonal antibody binding to glycoproteins C and D of herpes simplex virus types 1 and 2. AB - A competitive enzyme-linked immunosorbent assay was used to test for human antibodies to antigenic sites on herpes simplex virus (HSV) glycoproteins C and D, which are recognized by mouse monoclonal antibodies. Antibodies capable of blocking the monoclonal antibodies were detected in the human sera, and the inhibition of binding correlated with the histories of herpetic infections. The binding of monoclonal antibody to glycoprotein C of HSV type 2 was inhibited primarily by sera from patients with recurrent herpes genitalis; however, the binding of the monoclonal antibodies to gC of HSV type 1 was inhibited by sera from patients previously infected with either HSV type 1 or HSV type 2. The observations suggest that the antigenic sites defined by the mouse monoclonal antibodies are recognized by the human host. PMID- 2582150 TI - Double-stranded RNA-dependent protein kinase and 2-5A system are both activated in interferon-treated, encephalomyocarditis virus-infected HeLa cells. AB - Activation of the interferon-inducible, double-stranded RNA-dependent protein kinase was monitored in monolayer cultures of control and interferon-treated HeLa cells infected with encephalomyocarditis virus. The extent of phosphorylation in the intact cell of the alpha-subunit of eucaryotic protein synthesis initiation factor eIF2 by the kinase was determined for the first time in this type of system, using a two-dimensional immunoblot technique. Virus protein synthesis and the kinetics of activation of the ppp(A2'p)nA (n greater than or equal to 2) system were analyzed in parallel. Enhanced phosphorylation of eIF2-alpha was obvious at 9 h and increased by 12 h postinfection. ppp(A2'p)nA and ppp(A2'p)nA mediated rRNA cleavage were observed from 6 h. No viral protein synthesis was detected in cells in which a general inhibition of protein synthesis developed with time. It can be concluded that both the kinase and ppp(A2'p)nA system are active in interferon-treated, encephalomyocarditis virus-infected HeLa cells. PMID- 2582151 TI - Conservative management of testicular endodermal sinus tumor in childhood. AB - Endodermal sinus tumor is the most common testicular neoplasm in childhood. The management of children with this neoplasm remains controversial. We have treated prospectively 5 children with stage I endodermal sinus tumor with limited surgery and no adjuvant therapy. The median patient age at diagnosis was 21 months (range 5 to 24 months). All children underwent an inguinal orchiectomy with high ligation of the spermatic cord. Retroperitoneal node dissection was not performed in any case and no child received adjuvant chemotherapy or radiation therapy. All patients were well without evidence of recurrent disease at a median followup of 46 months (range 19 to 72 months). Because these tumors usually are localized at the time of diagnosis, rarely spread to the retroperitoneal nodes and have a biological marker in most cases, and because good salvage chemotherapy is available for patients with relapse, we believe that nonmetastatic testicular endodermal sinus tumors in children can be managed with radical orchiectomy alone. Retroperitoneal node dissection is not necessary and adjuvant therapy is not indicated if markers return to normal. Further treatment should be reserved for the rare child with relapse. PMID- 2582152 TI - The effects of a new serotonin receptor antagonist (ketanserin) on lower urinary tract function in patients with prostatism. AB - Ten male patients with prostatism, median age 63 years (range 50 to 70 years) were given an intravenous injection of a new serotonin antagonist, ketanserin, at a dose of 10 mg., and were investigated urodynamically before and after injection. A statistically significant increase in maximum and mean flow rates and a statistically significant decrease in urethral pressure profile measurements was observed. Supine CO2 cystometry showed no significant decrease in volumes of first sensation and bladder capacity. No subjective side effects were registered, but we observed a statistically significant decrease in mean blood pressure of 6.5 mm. Hg (range 5 to 14 mm. Hg). The mechanism behind the beneficial effect of ketanserin on micturition in prostatism is not yet known, but the results could explain an alpha blocking effect of the drug. PMID- 2582153 TI - Comparative sensitivities of diagnostic procedures used to detect bacterial kidney disease in salmonid fishes. AB - Kidney and spleen homogenates from each of 60 coho salmon (Oncorhynchus kisutch) and steelhead trout (Salmo gairdneri) were examined for detection of Renibacterium salmoninarum. The proportions of positives differed widely with the detection procedures used: in coho salmon, 5% were positive by the Gram-stain procedure, 10% by the direct fluorescent antibody test, 48% by bacteriological isolation, 65% by staphylococcal coagglutination, and 73% by counterimmunoelectrophoresis; in steelhead trout, 3% were positive by Gram-stain, 8.3% by fluorescent antibody, 17% by bacteriological isolation, and 67% by counterimmunoelectrophoresis. Renibacterium salmoninarum was not detected in either coho salmon or steelhead trout by immunodiffusion analysis. PMID- 2582154 TI - Histoplasmosis diagnosed on peripheral blood smear from a patient with AIDS. PMID- 2582155 TI - Molecular level view gives immune system clues. PMID- 2582156 TI - Atypical metastasis from prostate cancer. Clinical utility of the immunoperoxidase technique for prostate-specific antigen. AB - We review our experience with the immunoperoxidase technique of staining tissue for prostate-specific antigen in four patients with atypical metastases from prostate cancer. Our results indicate that this test is clinically useful for the diagnosis of metastatic prostate cancer in patients with an unsuspected primary prostate malignancy. Further, application of prostatic-specific antigen testing may confirm metastatic prostate cancer in atypical sites in patients with a previously diagnosed prostate malignancy. PMID- 2582157 TI - [Long-term prognosis of oral squamous cell carcinoma histologically judged to have been eliminated by the treatment with bleomycin alone]. AB - This study was intended to reveal the long-term prognosis in 21 patients with oral squamous cell carcinoma evaluated histologically as having disappeared by bleomycin treatment. Of 16 cases treated with bleomycin alone, recurrence was observed in 4, and cervical metastases in 2, with survival achieved for 5 years or more in 7 (more than 10 years in 3). No recurrence was observed in 5 patients in whom surgery was additionally performed after the bleomycin treatment, but cervical metastasis was found in one of them. In the cases with epithelial dysplasia after bleomycin therapy, recurrence and metastasis were frequent compared to those with normal epithelium, and this discrepancy was of statistical significance. It has been proved that there are long-term survivors among patients with oral carcinoma treated with bleomycin alone. PMID- 2582158 TI - [Serum levels and clinical evaluation of CA 19-9 in various diseases]. AB - We evaluated the clinical significance of serum CA 19-9 in various cancers, benign diseases and healthy controls. The percentage of positive cases for CA 19 9 (higher than 37 U/ml) was 83% in pancreas cancer, 78% in biliary tract cancer and 75% in urinary tract cancer. Benign diseases showed a low frequency of positive cases for CA 19-9, and their serum levels of CA 19-9 were low. Benign diseases with high serum levels of CA 19-9 were rarely seen, but they were easy to differentiate from malignant tumors by simultaneous examination of other tumor markers. In cancer patients with high serum levels of CA 19-9, CA 19-9 showed a weak positive correlation to CEA and ferritin. PMID- 2582159 TI - [A case of alpha-fetoprotein-producing gastric carcinoma with histologic features of embryonal carcinoma]. AB - A case of advanced gastric carcinoma in a 75-year-old female with highly elevated serum alpha-fetoprotein (AFP) (9050 ng/ml) is presented. A Borrmann 3 type tumor measuring 7 X 7 cm was located in the gastric antrum and directly invaded up to the radix of the superior mesenteric artery. Neither the preoperative CT scan nor close examination at surgery revealed any evidence of hepatic metastasis. The histological examination showed largely embryonal (atypical-cell) carcinoma. By immunoperoxidase staining, AFP and alpha-1-antitrypsin (AAT) immunoreactivities were identified in some carcinoma cells. Sixteen cases of AFP-producing gastric carcinoma reported in Japan were reviewed. PMID- 2582160 TI - [Treatment of malignant lymphoma in childhood]. PMID- 2582161 TI - [Biochemistry of the brain. f. Nucleic acids]. PMID- 2582162 TI - [Role of carbohydrate moieties in determining the antigenic properties of influenza C viral glycoproteins]. PMID- 2582163 TI - [Separation of modified amylase using electrophoresis and inhibitor methods]. PMID- 2582164 TI - [Column chromatographic analysis of serum amylase isozymes, with special reference to S type hyperamylasemia of liver cirrhosis]. PMID- 2582165 TI - [Choriocarcinoma and teratoma of the retroperitoneum--immunohistochemical investigation]. PMID- 2582167 TI - [Treatment of esophageal cancer with antineoplastic agents in ointment form]. PMID- 2582166 TI - [Ultrasonic evaluation of small hepatocellular carcinoma: on the diagnostic problems and the limits of detectability]. PMID- 2582168 TI - Preoperative hyperthermo-chemo-radiotherapy for esophageal carcinoma--analysis of 20 cases. PMID- 2582169 TI - Some characterization of the responses to substance P and other tachykinins in rabbit iris sphincter muscle. AB - Contractile responses to substance P, physalaemin and eledoisin, three members of the tachykinin family, were compared and characterized in rabbit iris sphincter smooth muscle. Eledoisin and physalaemin were approximately 5 times more potent than substance P, and the maximum responses to substance P and physalaemin were about 85 percent of those to eledoisin and carbachol. The contractile responses to the three tachykinins were not affected by tetrodotoxin (3 X 10(-6) M) and atropine (10(-6) M). The contractions induced by substance P and physalaemin were well sustained even after they were thoroughly washed out, whereas the eledoisin induced contraction was rapidly ceased by removing the agonist from the bathing medium. The sustained contraction evoked by substance P or physalaemin was strongly dependent on extracellular calcium ions. Phenoxybenzamine (2 X 10(-5) M, 10 min) selectively attenuated the response to eledoisin, but not substance P or physalaemin, and concomitant incubation with excess eledoisin (10(-7) M) significantly prevented the inhibitory effect of phenoxybenzamine. The difference between responses to eledoisin and to the other peptides, substance P and physalaemin, may suggest the existence of two different receptor subtypes for tachykinins in rabbit iris sphincter smooth muscle. PMID- 2582170 TI - Beta 1-adrenoceptor-mediated amylase release and cyclic AMP accumulation in rat parotid gland tissue. AB - The present study was carried out to determine the relationship of beta 1- and Beta 2-subtype to amylase release and cyclic AMP (cAMP) accumulation in rat parotid tissue. In in vitro experiments, beta-adrenergic agents (isoproterenol and dobutamine)-induced amylase release and cAMP accumulation were all completely inhibited by the beta 1-antagonist metoprolol, but incompletely inhibited by the beta 2-antagonist butoxamine. The beta 2-agonist procaterol caused little or no amylase release or cAMP accumulation. Our results suggest that both amylase release and cAMP accumulation in rat parotid tissue may be selectively induced by beta 1-adrenergic stimulation. PMID- 2582171 TI - Effects of idebenone (CV-2619) on metabolism of monoamines, especially serotonin, in the brain of normal rats and rats with cerebral ischemia. AB - The effects of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone, CV-2619) on the contents, turnover, release and uptake of monoamines, especially serotonin (5-HT), in various brain regions of Wistar rats were studied in vivo and in vitro. In normal rats, an intraperitoneal (i.p.) dose of 100 mg/kg of CV-2619 had no significant effect on the levels of norepinephrine (NE), dopamine (DA) and their metabolites, and 5-HT in the brain regions examined, but it increased the levels of 5-hydroxyindole-3-acetic acid (5-HIAA), the main metabolite of 5-HT, in many brain regions. In rats with cerebral ischemia, a low dose (10 mg/kg, i.p.) of CV-2619 normalized the decreased levels of 5-HIAA in the cerebral cortex, hippocampus, diencephalon and brain stem. A 5-HT biosynthesis inhibitor, DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.), decreased the levels of 5-HT in all brain regions to one-third of the control levels 24 hr after administration in normal rats. CV-2619 (10, 30 or 100 mg/kg, i.p.), administered 24 hr after the treatment with PCPA, accelerated the PCPA-induced 5-HT decreases in the hippocampus, diencephalon and brain stem in a dose-dependent manner. In vitro CV-2619, like p-chloroamphetamine (PCA), stimulated 5-HT release from slices of the hippocampus and diencephalon. CV-2619 slightly inhibited and PCA markedly inhibited 5-HT uptake into hippocampal slices. The mechanism of the 5-HT releasing action of CV-2619 in hippocampal slices seems to be mediated through endogenous calcium. These results suggest that CV-2619 has an enhancing effect on the turnover of 5-HT in the hippocampus, diencephalon and brain stem of rats. PMID- 2582172 TI - Involvement of calcium in the release of immunoreactive beta-endorphin-like peptide from dispersed cells of the neurointermediate lobe of the rat pituitary gland. AB - The presence of Ca2+ in the incubation medium was required for stimulation of the release of the immunoreactive beta-endorphin-like peptide (IR-beta-EP) from the dispersed cells of the neurointermediate lobe of rat pituitary gland by adenosine 3',5'-monophosphate (cAMP) analogs, a phosphodiesterase inhibitor, L isoproterenol, cholera toxin and forskolin. The basal release observed in the absence of the stimulants was also dependent on the addition of Ca2+. A calcium antagonist (verapamil) inhibited the effects of the stimulants. A calcium ionophore (A23187) enhanced the release of IR-beta-EP, but did not stimulate the formation of cAMP. These findings suggest that Ca2+ has the essential role in the release of beta-endorphin from the neurointermediate lobe of rat pituitary gland. PMID- 2582174 TI - In vitro and in vivo formation of 7-(2'-carboxyethyl)guanine from the liver carcinogen 1-nitroso-5,6-dihydrouracil and its reactions with water and methanol. AB - Base-catalyzed hydrolysis of the potent liver carcinogen 1-nitroso-5,6 dihydrouracil [(NDHU) CAS: 16813-36-8] afforded 3-hydroxypropionic acid and acrylic acid in 72 and 6% yield, respectively. The base-catalyzed methanolysis of NDHU gave quantitative yields of 3-methoxypropionic acid and methyl carbamate. These results indicate that base-catalyzed NDHU decomposition produces a 2 carboxyethyl carbonium-ion-type intermediate. When 3H-labeled NDHU was reacted at pH 8 with DNA and RNA, 7-(2'-carboxyethyl)guanine (CEG) was detected in the hydrolysate and was identified by its cochromatography with authentic CEG in five (for DNA) or three (for RNA) systems and by a reverse isotope-dilution procedure. Radioactively labeled CEG (identified as before) and five other labeled chromatographic fractions were present in liver DNA and RNA hydrolysates after [3H]NDHU was gavaged into MRC Wistar rats. These fractions persisted in the liver DNA for various times up to 33 days after the gavage. The CEG fraction was 94% of the radioactivity in DNA reacted in vitro, but it reached only 21% of the radioactivity in the liver DNA. The results are related to a study on single strand breaks produced by NDHU in rat liver DNA. PMID- 2582173 TI - Monoclonal antibody recognizing human melanoma-carcinoma cross-reacting oncofetal antigen epitopically associated with carcinoembryonic antigen. AB - By fusion of mouse NS1 myeloma cells with splenocytes from a BALB/c mouse immunized with human melanoma cells, an IgG1 monoclonal antibody, designated as 140.72, was produced. By the mixed hemadsorption antibody binding assay, 140.72 was shown to react with 17 of 20 melanoma cell lines and with 5 of 14 carcinoma cell lines. This antibody also reacted with 3 of 3 normal melanocyte cultures in much lower titers. It did not react with any of 35 other normal and malignant lines, including neuroblastoma, glioblastoma, sarcoma, teratoma, fibroblast, and lymphoid cell lines. Absorption with fresh melanoma and carcinoma homogenates confirmed the results of direct tests. Fetal reactivity of antibody 140.72 was determined by positive absorption with 10 of 11 tissue homogenates derived from different fetuses of 10-16 weeks' gestation. The reactivity of this antibody was completely removed by absorption with a highly purified preparation of carcinoembryonic antigen (CEA) derived from a colon carcinoma. The antigenic activity was detected in the culture medium of reactive cell lines. Immunoprecipitation analyses of melanoma and carcinoma cells indicated that the antigenic determinant recognized by antibody 140.72 is on a glycoprotein with an apparent molecular weight of 95,000-150,000 common to both serologically reactive cell types. Additionally, a 200,000-molecular-weight glycoprotein corresponding to the CEA molecule was detected only on the reactive carcinoma cells. These data confirmed previous findings obtained with polyclonal anti-CEA antisera for the existence of shared CEA-related antigenic determinants on human carcinomas and melanomas and provided additional molecular characterization of these glycoproteins. Further characterization of the molecules bearing the antigenic determinant recognized by antibody 140.72 should be performed with a view to exploring its potential in the immunodiagnosis and immunotherapy of patients with melanoma. PMID- 2582175 TI - Light and electron microscopic studies of perineural invasion by esophageal carcinoma. AB - Light and electron microscopic findings on perineural invasion by human esophageal squamous cell carcinoma are reported. Perineural invasion was observed histologically in 30 of a total of 129 cases (23%) of esophageal squamous cell carcinoma and in 11 of the 24 cases (46%) in which tumors infiltrated other organs by passing through the esophageal adventitial layer. Electron microscopic observation showed that the perineurium of peripheral nerves was completely surrounded by carcinoma cells and that marked degeneration and loss of perineural cells occurred. Irregularly thickened basal laminae were detected in the perineurium. For nerves incompletely surrounded by carcinoma tissue, the free portion of the perineurium revealed degenerative findings similar to those for completely surrounded nerves. Cytoplasmic projections of the leading margin of the invading cancer tissue were located in the degenerated perineurium, contained many lysosomes, and were not always surrounded by basal laminae. These observations suggest that invading carcinoma tissue actively contributes to the degeneration of the perineural sheath and that the special pattern of carcinoma tissue surrounding the peripheral nerves results from infiltration along the degenerated sheath of the perineurium. PMID- 2582176 TI - Experimental chemotherapy (L1210) with 5-aza-2'-deoxycytidine in combination with pyran copolymer (MVE-4), an immune adjuvant. AB - The life-span of CDF1 (BALB/c X DBA/2)F1 mice that received intraperitoneal implants with 10(5) L1210 tumor cells was prolonged to 23 days (compared to 8 days in L1210 tumor-implanted, untreated mice) when 5-aza-2'-deoxycytidine (DAC) was given to the mice after the tumor cells were allowed to metastasize (3 days after implant); DAC, however, resulted in no cures (survival beyond 48 days). When the pyran copolymer MVE-4, an immune adjuvant, was given the day after DAC, 25% of the mice treated were cured and the life-span of dying mice was increased by 7 days. When MVE-4 was repeated weekly for 4 weeks, 79% of treated mice were cured. Cured mice were able to resist a subsequent challenge of approximately 2 logs of L1210 cells. This combination of DAC plus MVE-4 was more effective than DAC alone only if the tumor cells and MVE-4 were given intraperitoneally. When this combination was repeated weekly, it became lethally toxic after 3 weeks, but only to L1210-tumor-bearing mice and not to normal mice. When DAC alone was given 2 days before tumor implant, it induced an apparent immune effect so that mice could resist a subsequent challenge of approximately 1.5-2 logs of L1210 cells. Support for part of the antitumor action of DAC exerted through the immune system was given by data that show that later treatment with noncurative doses of DAC is superior to early treatment in mice with large L1210 tumor burdens. PMID- 2582177 TI - [Initial results of clinical research on a tabletted form of ethacizin (the diethylamino analog of ethmozine) in ventricular arrhythmias]. AB - The clinical effectiveness, pharmacodynamics and some pharmacokinetic aspects of a new antiarrhythmic drug ethacyzin (a diethylamine analogue of ethmozin) were studied, using diurnal electrocardiographic monitoring and exercise testing, in 50 patients with frequent and chronic ventricular heart rhythm disorders. The drug had positive antiarrhythmic effect in 87-90% of patients treated with single 100-150 mg oral doses and courses of 150-300 mg daily (the mean dose being 200 +/ 50 mg). With a single oral dose of 100 mg ethacyzin, the onset, peak and overall duration of its therapeutic effect were noted at 0.5-1, 1.5-2 and 6-8 hours, respectively. The minimal therapeutic plasma ethacyzine concentration was 40-70 ng/ml. Both in acute testing and during treatment courses, the drug significantly expanded the P wave, the P-Q interval and the QRS complex of the electrocardiogram, without affecting heart rate or Q-T duration, the magnitude of the resulting change in the said parameters depending on the dose administered and the antiarrhythmic effect of ethacyzin. PMID- 2582178 TI - [Visualization of parathyroid adenomas and the parathyroid glands (review of the literature)]. PMID- 2582180 TI - A classification of essential hypertensive patients according to the erythrocyte Na transport abnormalities: an application for monitoring the antihypertensive response to cicletanide. AB - We have studied the kinetic properties of the interaction of internal Na with four different Na transport pathways (ouabain-sensitive Na, K pump, bumetanide sensitive Na,K cotransport, Li:Na countertransport and passive Na permeability) in erythrocytes from 197 essential hypertensive patients. This study permitted us to classify 168 of the 197 hypertensives studied into the following groups: Pump hypertensives-six patients showing low pump affinity for internal Na and high maximal pump rate; Co - hypertensives -95 patients characterized by low cotransport affinity for internal Na and low or normal maximal outward cotransport rate. Counter + hypertensives - 35 patients characterized by low countertransport affinity for internal Na and high maximal countertransport rate; and Leak + hypertensives - 32 patients showing increased passive Na permeability. Having studied the apparent affinity of the Na,K cotransport system for external K we divided the co - hypertensives into three subgroups (symmetric, asymmetric or antisymmetric) according to the presence of low, normal or high K affinity. Forty-five hypertensive patients were submitted to antihypertensive treatment with a new diuretic and antihypertensive drug, cicletanide. Preliminary results indicate that one of the factors involved in the antihypertensive efficiency of the compound is the subgroup to which the hypertensive belongs. PMID- 2582182 TI - The sodium pump and energy regulation: some new aspects for essential hypertension, diabetes II and severe overweight. AB - There is a growing evidence for that in modern societies the function of the cellular sodium-potassium pump (membrane-bound Na+ K+ ATPase) in several tissues in man cannot respond adequately to demands. This is not seen in any other free living vertebrates on this earth. The clearly unphysiological very high intake of sodium-chloride (salt) and also alcohol is definitely playing an important role in the development of the common degenerating metabolic aberrations, e.g. essential hypertension, diabetes II and severe over-weight, in man. The special and overall important role of the sodium-potassium pump for optimal cellular function and regeneration with special reference to the vascular tissues is presented and discussed. PMID- 2582184 TI - [Dynamics of blood fibronectin in patients with myocardial infarct]. PMID- 2582183 TI - [Photometric methods of laboratory studies and their application to medical microanalysis]. PMID- 2582181 TI - Sodium transport and red cell deformability. AB - Inhibition of the Na-K pump by a circulating factor is thought to be of importance in the pathophysiology of essential hypertension. We tested the correlation between an inhibition of the Na-K pump by digoxin and the deformability of red blood cells (RBC) both in vitro and in vivo. Erythrocytes were incubated with digoxin (0-1.3 mumol/l) for 1 h at 37 degrees C. Highest concentration of digoxin (0.13 and 1.3 mumol/l) significantly diminished Na-K pump activity, measured by uptake of 86rubidium (Rb). There was a parallel decrease in red cell filtrability. In nine healthy volunteers, intake of digoxin (0.2 mg b.i.d.) over a 5-day period did not alter red cell deformability and uptake of 86Rb. Taken together, inhibition of the Na-K pump in vitro correlates with a reduced red cell deformability. However, this occurs at a toxic dosis of digoxin. PMID- 2582185 TI - [New method of evaluating the transport function of serum albumin]. PMID- 2582179 TI - [Hepatitis non-A, non-B: epidemiologic, clinical, serologic and morphologic aspects]. AB - Hepatitis non-A, non-B (HNANB) is due to one or more transmissible agents, probably viruses. Epidemiologically, HNANB is transmitted predominantly by transfusion of blood or plasma derivatives, and percutaneous inoculation, but a non-percutaneous transmission by the fecal-oral route is also established. However, despite 10 years of intense world-wide research, the transmissible agent, or agents, have not been identified and there are no serological assays for either an antigen or an antibody that can be used to detect this infection. The clinical diagnosis of HNANB remains, therefore, a diagnosis of exclusion mainly of hepatitis A and B, Epstein-Barr virus, cytomegalovirus and drug-induced liver disease. In contrast to hepatitis A and B, the clinical and biochemical course of HNANB tends to be less severe and the proportion of asymptomatic and anicteric cases is higher, but fulminant hepatitis and fatalities also occur. Typically, there is a fluctuating waxing and waning pattern of the serum aminotransferase activities in HNANB. HNANB has a relative high tendency to progress to a chronic stage. The exact frequency of HNANB-induced liver cirrhosis and convincing evidence for an association with hepatocellular carcinoma cannot be assessed, although the persistence of the infectious agent in chronic HNANB and the existence of a chronic asymptomatic carrier state have been proved. By light microscopy there is a broad morphologic spectrum of acute and chronic viral hepatitis, but no single pathognomonic lesion exists that allows a reliable distinction to be made of HNANB from hepatitis A and B. Electron microscopy of liver biopsy specimens of chimpanzees, experimentally infected with HNANB agents, permits the visualisation of cytoplasmic changes, which appear to be specific for infection with HNANB viruses. In human liver biopsy specimens from patients with HNANB, identical ultrastructural cytoplasmic changes could not consistently be demonstrated. In contrast, intranuclear aggregates of spherical and tubular particles measuring 20-29 nm, first described in experimental HNANB in chimpanzees, have been repeatedly demonstrated in acute and chronic HNANB in man. These nuclear particles have been considered as compelling evidence of human HNANB infection. The specificity has been challenged, however, by the demonstration of identical particles in other viral and non-viral hepatopathies and in liver biopsies of healthy volunteers. By immune electron microscopy, a multiplicity of virus-like particles are described in association with HNANB.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2582186 TI - [Qualitative and quantitative distribution of proteins in normal human cerebrospinal fluid based on polyacrylamide gel disc electrophoresis data]. PMID- 2582187 TI - [Determination of insulin in blood using the Insulin RIA Kit (Hungary)]. PMID- 2582188 TI - [Isolation of orosomucoid from human blood plasma and preparation of its antiserum]. PMID- 2582189 TI - [Disorders of creatine metabolism in patients with bronchial asthma]. PMID- 2582190 TI - [Cytologic studies directed to determining the delivery date in women]. PMID- 2582191 TI - [Cytologic characteristics of carcinoid of the lung]. PMID- 2582192 TI - [Cytophotometric and autoradiographic study of transplantable strains of hepatoma, lung cancer, melanoma and sarcoma. 1]. PMID- 2582194 TI - [Use of gas-liquid chromatography to study non-clostridial anaerobic infection in a surgical clinic]. PMID- 2582193 TI - [Case of complete Alder's anomaly of the peripheral blood leukocytes]. PMID- 2582195 TI - [Mechanism of identification tests for Pseudomonas aeruginosa and their simplified modifications]. PMID- 2582196 TI - [Current nomenclature of bacteria in applied microbiology]. PMID- 2582197 TI - [Effect of specimen workup on detection of Shigella antigens]. PMID- 2582198 TI - [Determination of the toxigenicity of staphylococci by the method of counterdiffusion in agar and its taxonomic value in identifying Staphylococcus aureus strains]. PMID- 2582199 TI - [Value of homogenizing sputum for isolation of Mycobacterium tuberculosis using electrophoresis]. PMID- 2582201 TI - [Evaluation of different methods of studying microbial contamination of objects in the external environment]. PMID- 2582200 TI - [Use of hemin as a stimulator of the growth of the plague microbe]. PMID- 2582202 TI - [Summation of the discussions on the problem of personnel in laboratory service]. PMID- 2582203 TI - [Evaluation of the economic benefit of quality control of laboratory studies]. PMID- 2582204 TI - [Recommendations on the use of "Lachema" (ChSSR) and "Fermognost" (GDR) reagent kits for determining total lactate dehydrogenase activity and its urea-resistant fractions]. PMID- 2582205 TI - [Role of the laboratory physician in the diagnostic process]. PMID- 2582206 TI - Effects of SK&F 82526 and SK&F 83742 on the renal vascular dopamine receptor. AB - The renal vascular effects of benzazepine derivatives were studied on the isolated perfused rat kidney in the presence of phenoxybenzamine and sotalol after contraction of the vascular bed with prostaglandin F2 alpha. SK&F 82526 was a very potent dopaminomimetic drug (ED50 = 7.6 +/- 0.8 X 10(-9) M) on the renal vascular dopamine receptor. It displayed partial agonist activity (similar to SK&F 38393) and was devoid of alpha-adrenomimetic effects. SK&F 83742 was a potent dopaminolytic drug. It antagonized dopamine-induced relaxation of the renal vascular bed in a competitive way, with an apparent pA2 of 7.47 +/- 0.23. PMID- 2582207 TI - Modified Hodgkin-Huxley gating kinetics of sodium activation in giant axons of squid (Doryteuthis bleekeri). AB - The probabilities m of the sodium activation gate being open are shown to fit experimentally-determined running integrals Qg of recordings of the colchicine sensitive fraction of the asymmetry current, within the Hodgkin-Huxley framework that the gate could have only two conformations, open and closed. Using the Hodgkin-Huxley framework, we are obliged to assume that the transition velocities, alpha m and beta m, between the open and closed gates depend not only on membrane potentials V but also on the time after a potential step was externally applied. We introduce the following functions of alpha m and beta m. (sequence in text) where VH, td and tau p stand for holding potential, constant delay time of 10 microseconds, and transit time of the transition velocity of alpha m (or beta m) from its initial value alpha om (or beta om) to its final steady value alpha infinity m (or beta infinity m), respectively. The transit time tau p was found to be potential-dependent; typically it was 30 microseconds at -20 mV, and 100 microseconds at 20-40 mV. The values of alpha infinity m, alpha om, beta infinity m and beta om were found to be in reasonable agreement with those obtained by others, under the Hodgkin-Huxley assumption that the gate followed first-order kinetics. The requirement of new parameters, tau p and td, in the transition velocities was discussed in a relation to a membrane model where a voltage-receptor and a sodium channel macromolecule are spatially separated but functionally connected through underlying cytoskeletons (Matsumoto, 1984). PMID- 2582208 TI - Interpretation of 1/f fluctuations in ion conducting membranes. AB - The main objective of this work is to resolve some uncertainties associated with the analysis of conductance fluctuations that exhibit 1/f spectral density. To this end, we derive mathematical conditions under which a discrete summation of Lorentzian functions best approximates a strictly 1/f density over a given frequency range. The intrinsic errors associated with spectral density estimates are considered and used as a constraint to determine the smallest number of optimally chosen Lorentzians required to fit a 1/f-like spectrum in a statistically acceptable manner. The results provide criteria concerning the extent to which mechanisms generating a strictly 1/f spectra may be distinguished from those generating sums of Lorentzian spectra. It is found, in particular, that 1/f-like fluctuation spectra observed in a variety of biological and model membranes may well arise from the summation of a few Lorentzian components having appropriate amplitudes and corner frequencies. Consideration of physically realistic models of ion conductive channels indicates that 1/f-like conductance fluctuation spectra could originate naturally as a direct consequence of thermodynamic constraints upon the coefficients of Lorentzian components. PMID- 2582209 TI - Neuroendocrine neoplasms of the bronchopulmonary tract. A classification of the spectrum of carcinoid to small cell carcinoma and intervening variants. AB - Eighty-one primary pulmonary neuroendocrine neoplasms were assessed by the classification of Gould and associates. The neuroendocrine features of these tumors were studied by a combination of conventional light microscopy, electron microscopy, and immunohistochemical staining for hormonal substances and neuron specific enolase. In each case, clinical follow-up was obtained to test the prognostic value of this new pathological classification. This study indicated that bronchial carcinoids are very low-grade neuroendocrine neoplasms that are locally invasive and only occasionally metastasize late in their course. Well differentiated neuroendocrine carcinomas are relatively low-grade carcinomas that either present with or subsequently develop nodal or distant metastases in 73% of patients. Intermediate cell neuroendocrine carcinomas are highly aggressive tumors often mistakenly called "large cell undifferentiated carcinoma." Their clinical course is comparable to that of small cell neuroendocrine carcinomas, which has a mean survival of 9 months. The different clinical courses of these tumors demonstrate the predictive value of the proposed classification. It appears particularly valuable to identify well-differentiated neuroendocrine carcinoma as a low-grade carcinoma, distinct from true bronchial carcinoids. This classification may resolve some discrepancies regarding the therapy for and prognosis of "carcinoids" and their presumed variants. PMID- 2582211 TI - Normal counterparts of hairy cells and B-prolymphocytes in the peripheral blood. An ultrastructural study with monoclonal antibodies and the immunogold method. AB - The morphological and membrane phenotypic characteristics of normal peripheral blood B-lymphocytes were studied at ultrastructural level by means of the immunogold method with the following McAb: anti-HLA-Dr (OKIa and FMC4), FMC7, OKT10, and alpha HC1 and alpha HC2, reactive with HCL cells. Five morphological subsets of B-lymphocytes were identified: (i) 40% had a high nuclear cytoplasmic ratio, well condensed chromatin and small pale granules localised in one area of the cytoplasm, these cells expressed HLA-Dr and did not react with any of the other McAb; (ii) 40% had a prominent nucleolus, variable amount of chromatin condensation and localised granules, these cells were HLA-Dr positive and some of them expressed FMC7 as do the cells of B-PLL; (iii) 10% had a villous outline and variable numbers of polyribosomes scattered throughout the cytoplasm, some of these cells resembled morphologically HCL cells and were HLA-Dr +, FMC7 +, alpha HC1 +, alpha HC2 + and OKT10 +/-. The remaining two types of B-cells (10%) had the morphology of antibody secreting cells with parallel arrays of endoplasmic reticulum and some displayed electron dense granules in the Golgi zone. These cells were: (iv) lymphoplasmacytoid, the more common type, which were HLA-Dr +/-, FMC7-, alpha HC1-, alpha HC2 + and OKT10 +/-, and (v) plasma cells which were positive only with OKT10. The similarities in morphology and membrane markers between two of the subsets defined in this study and the cells of B-PLL and HCL suggest that they may represent normal counterparts of these B-cell malignancies. PMID- 2582210 TI - Iloprost (ZK36374), a stable analogue of prostacyclin, preserves platelets during simulated extracorporeal circulation. AB - Contact between blood and synthetic surfaces of an extracorporeal circuit results in extensive alterations in platelet function. These platelet abnormalities have been reproduced in vitro by recirculating heparinized (5 units/ml) human blood at 37 degrees C in a silicone rubber circuit (0.1 m2) containing a spiral coil membrane oxygenator (0.9 m2). During control recirculation trials, platelet counts fell to 29% +/- 8% (mean +/- standard error of the mean) of initial levels within 30 minutes, and sensitivity to the soluble agonists, adenosine diphosphate and epinephrine, disappeared. Plasma levels of the platelet-specific protein platelet factor 4 rose to 2,600 +/- 200 ng/ml, indicating extensive platelet granule release. Similarly, plasma concentrations of thromboxane B2 rose from less than or equal to 100 pg/ml to 500 +/- 200 pg/ml at 120 minutes, and transmission electron microscopy demonstrated disruption of platelet subcellular architecture. In contrast, when ilioprost, a stable prostacyclin derivative (1 ng/ml), was added to the circuit prior to recirculation, the thrombocyte count remained at 85% +/- 4% of initial values. Platelets incubated or recirculated for 2 hours in the presence of iloprost responded normally to both adenosine diphosphate and epinephrine after separation from the drug by gel-filtration. Furthermore, plasma concentrations of platelet factor 4 remained below 300 ng/ml, plasma levels of thromboxane B2 failed to reach detectable levels, and platelet ultrastructure remained intact. Thus, iloprost effectively preserves the circulating platelet count, prevents platelet granule release, and preserves platelet functional and morphological integrity during simulated extracorporeal circulation. PMID- 2582213 TI - Batrachotoxinin-A N-methylanthranilate, a new fluorescent ligand for voltage sensitive sodium channels. AB - Batrachotoxin and its derivatives have become important tools for the study of membrane excitability by virtue of their effects on voltage-sensitive sodium channels. Recent studies have shown that the 2,4-dimethylpyrrole carboxylate ester normally occurring in the 20-alpha position of batrachotoxin may be replaced by a benzoate moiety without loss of activity. We have now extended this series of active batrachotoxin derivatives and report here the synthesis of batrachotoxinin-A 20-alpha-N-methylanthranilate. The new fluorescent compound is highly toxic (LD50 approx. 15 micrograms/kg, i.p. mouse) and binds to the same receptor site of voltage-sensitive sodium channels as batrachotoxin with an equilibrium dissociation constant Kd = 180 nM (in the presence of scorpion toxin). These fluorescence and binding properties have been exploited to achieve successful visualization of sodium channels at mammalian nodes of Ranvier. Batrachotoxinin-A 20-alpha-N-methylanthranilate should prove to be a useful compound for studies of sodium channel distribution and for investigations of the microenvironment of the batrachotoxin binding site. PMID- 2582212 TI - Role of cyclic AMP in antiserum-induced growth inhibition of murine leukemia L5178Y cells. AB - Heat-inactivated rabbit antiserum, in the absence of complement, induced a 1.5-2 fold increase in cyclic AMP levels in target cells L5178Y leukemia lymphoblasts within 10-20 min after the experiment. This change preceded the previously reported delayed inhibitory effects of antiserum on cell growth such as inhibition of RNA, DNA, and protein synthesis and cell proliferation, suggesting that cyclic AMP may be one of the mediators of the antigen-antibody reactions which occur at the cell surface. Furthermore, the addition of cyclic GMP or excess calcium to either antiserum or cyclic AMP-treated cultures alleviated the growth inhibitory effects of either antiserum or cyclic AMP, substantiating further the hypothesis proposed. PMID- 2582214 TI - The physiologic interferon response. VI. Interferon activity in human plasma after a meal and drinking. AB - Interferon activity in plasma was found negligible in the morning and slightly increased in the afternoon. However, because of the wide variability of the results, the difference was not statistically significant even though the existence of a circadian rhythm appears possible. The afternoon increase of IFN activity could be at least in part due to increased abdominal lymphatic drainage following digestion and absorption. In fact, it has been shown that there is a significant transient increase in IFN plasma level 2 hours after a fat-rich meal or drinking 700 ml of water. IFN activity was due to acid-labile IFN-alpha. This is another, yet indirect, indication of the existence of the physiologic IFN response that entails a localized production of lymphomonokines with limited spillover in the circulation. PMID- 2582215 TI - Monoamine metabolites in human cerebrospinal fluid: indicators of neuronal activity? AB - Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been widely used as indicators of the level of functional activity in the central monoaminergic neuronal pathways. This article reviews the relationship between the turnover of the neurotransmitter monoamines noradrenaline, serotonin, and dopamine, and the concentrations in CSF of their principal metabolites, 3-methoxy 4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA). It attempts to summarise what is known of the effects of various illnesses and drug treatments on the concentrations of these metabolites. PMID- 2582216 TI - Value of monitoring amylase activities in patients with pancreatitis. PMID- 2582217 TI - Antigenic heterogeneity of European Borrelia burgdorferi strains isolated from patients and ticks. PMID- 2582218 TI - Inosine pranobex. PMID- 2582219 TI - Prospective screening for Down syndrome using maternal serum AFP. PMID- 2582220 TI - Association of Whipple's disease with HLA-B27. PMID- 2582221 TI - Fc gamma-receptor blocking antibodies in hyperimmune and normal pooled gammaglobulin. PMID- 2582222 TI - [Anterior single-stage resection with a manual suture as the standard operation of the proximal and middle third of the rectum]. AB - Of a total of 146 restorative resections 129 one-stage anterior resections were performed in a series of 203 tumours of the rectum. The hand-sutured one-layer anastomosis, well established for the upper third of the rectum, can be equally well effected after resection of the middle third. For this purpose the dissection of the extraperitoneal rectum is carried down as far as to the pectinate line, comparable to the abdominal phase of rectal excision. When the anococcygeal raphe is cut the pectinate line becomes visible upon traction and the anastomosis is readily established from within the abdomen. After release of traction it glides down into it's narrow final embedment in the depth of the pelvis from which a potential dehiscence never becomes apparent before the 7th postoperative day. By this time conservative management without protective colostomy is possible, provided absorbable suture material and adequate drainage are used. Dehiscence rate was 12.4%, operative mortality 1.5%. Single components of reliability of the anastomosis are particularly well visualized and controlled with the hand-suture technique. PMID- 2582223 TI - Neurotensin enhances estradiol induced DNA synthesis in immature rat uterus. AB - Systemic administration of Neurotensin, a tridecapeptide, in immature rats treated with estradiol benzoate significantly enhances uterine DNA synthesis as reflected by the incorporation of 3H-thymidine. The peptide may have a direct action on the uterus. Substance P, a related peptide, had no effect on uterine DNA synthesis. PMID- 2582225 TI - [Conducting practical exercises in surgery]. PMID- 2582224 TI - Characterization of voltage-sensitive calcium channels in a clonal pituitary cell line. AB - We have pharmacologically characterized voltage sensitive calcium channels (VSCCs) in GH3 cells, an anterior pituitary clonal cell line known to secrete prolactin and growth hormone. Raising the medium K+ concentration from 5 to 50 mM caused an immediate increase in net 45Ca2+ uptake which remained apparent over a 15 minute time course. 45Ca2+ uptake was maximally stimulated nearly 10-fold over basal levels. This K+-induced stimulation of Ca2+ uptake was not prevented by 10 5M tetrodotoxin or by replacing sodium with choline in the assay medium. Ca2+ uptake was, however, inhibited by several VSCC antagonists: nitrendipine, D-600, diltiazem and Cd2+. Further, the novel dihydropyridine VSCC agonists, BAY K8644 and CGP 28392, enhanced 50 mM K+-stimulated 45Ca2+ uptake and these effects were blocked by nitrendipine. PMID- 2582226 TI - Basic characterization of a Pseudomonas aeruginosa PAO1 bacteriophage. AB - A bacteriophage of Pseudomonas aeruginosa PAO1 was characterized. Bacteriophage PIK was found to adsorb on the cell wall of the host organism. Electron microscopy of the phage PIK revealed that it had a bipyramidal hexagonal prismatic head of 110 nm in diameter, a tail which was 158 nm long and a tail plate of 47 nm width. This paper describes its basic characters, and a quantitative study was made of its adsorption to exponential phase cells of two different strains of P. aeruginosa. PIK was found to contain double stranded DNA and it appears to be virulent towards its host, P. aeruginosa PAO1. It was classified into the group of phages possessing a contractile tail. PMID- 2582227 TI - Expression of organ-specific antigens on capillary endothelial cells. AB - Our central thesis is that the endothelial cells which line capillaries of various organs are not all alike. Using monoclonal and conventional antibodies we demonstrate that capillary endothelial cells express on their cell surface an array of antigens that manifest organ selectivity. Brain-derived endothelial cells possess brain-associated antigens, ovary-derived endothelial cells share antigenic markers with other ovarian cells, and lung-derived endothelium possesses antigens that are primarily expressed on cells of the lung. Our experiments lead us to suggest that organ-associated determinants on the endothelial cell surface may play a role in the selective adhesion of tumor cells during metastasis, in site-limited vascular pathology, and in the regionally limited release of angiogenesis-induced factors. PMID- 2582228 TI - Perturbation of fibrinolysis inhibitors in progressive systemic sclerosis. AB - Significance of fibrinolysis in pathophysiology of progressive systemic sclerosis (PSS) has been the subject of much speculation. Renal disease in PSS was associated with significant depression of an inhibitor of fibrinolysis, antithrombin III (ATIII), independent of general disease activity. Association of ATIII depression with plasminogen consumption supports an active role for plasmin or another ATIII-inhibitable enzyme in the pathophysiology of renal disease in PSS, and may explain the thrombotic tendency and propensity for fibrin deposition. PMID- 2582229 TI - Model of anion and monovalent cation transport as neutral ion pairs through lipophilic water channels of the Na,K ATPase complex. AB - A model of anion and monovalent cation transport through a lipophilic water channel of the Na,K ATPase complex is presented. Literature data for the Na,K ATPase cation binding sites are combined with data for the anion binding sites of Band 3 to obtain adjacent cation and anion combining sites at the inner and outer channel mouths. Cations and anions form neutral ion pairs or undissociated acids at these sites and then partition much more favorably into lipophilic channel water, passing through the channel in diffusive fashion. Cation movements in an "uphill" direction occur without an enzyme translocating moiety and its specific energetic requirement. The pertinent factors are the exclusion of unpaired cations by the tight channel and the site selectivity or pickup ratios for Na/K at each side which dominate over bulk and transmembrane concentration ratios. ATP hydrolysis provides phosphate for ion pairing. PMID- 2582230 TI - Hospice palliative care. PMID- 2582231 TI - [Initial results of studying the lead concentration of the deciduous and permanent teeth of residents of Turin and the Province. I]. PMID- 2582232 TI - [Experimental studies on regeneration of the pancreas--morphological and functional restoration of the remnant pancreas after major pancreatectomy]. AB - In order to elucidate a regeneration of the pancreas, morphological and functional changes after major pancreatic resection were sequentially investigated in dogs. Within the first week after major pancreatectomy, the acinar cell division occurred, followed by hypertrophy resulting in an increase of the weight of the remnant pancreas. The regeneration rate correlated with the resection rate, glucose tolerance test, and insulin secretion of the remnant pancreas. Immediately after resection of more than 92% of the pancreas, severe diabetes and diarrhea developed. The regeneration rate was 29.9 +/- 6.03% (mean +/- SD) three to six weeks after surgery, without any recovery of the exocrine function. After twelve weeks following resection of 74 to 92% of the pancreas, so called Sandmeyer's diabetes developed. The regeneration rate was 45.3 +/- 4.22% in the nondiabetic group, accompanied with a good recovery of the exocrine function, but in the diabetic group it revealed regeneration rate of 15.4 +/- 2.39% with less recovery of the exocrine function. When less than 74% of the pancreas was resected, no significant changes were observed in both morphological and functional studies in the remnant pancreas with regeneration rate of 5.5 +/- 6.62%. PMID- 2582233 TI - [The peptidyltransferase center of ribosomes--what is it?]. AB - The recent data on the interaction of model substrates and substrate-like analogs with acceptor and donor sites of 70S and 80S ribosomes are considered in terms of peptidyl transferase center models suggested earlier. PMID- 2582234 TI - [Contacts of ribosomal proteins with tRNAPhe and 16S RNA in analogs of the 30S initiation complex]. AB - Direct RNA-protein contacts have been studied by means of ultraviolet-induced (254 nm) cross-links inside complexes of NAcPhe-tRNAPhe, Phe-tRNAPhe and deacylated tRNAPhe with poly(U)-charged 30S subunit of Escherichia coli ribosome. In the first two complexes tRNA directly contacts with the similar sets of proteins (S4, S5, S7, S9/S11; S6 and S8 are found only in the second complex). These sets are similar to that in the fMet-tRNAfMet X 30S X mRNA complex, evidencing similar disposition of tRNAs in these three complexes. 16S RNA contacts in free 30S subunit mainly with proteins S4, S7 and S9/S11. In both complexes, containing NAcPhe-tRNAPhe and Phe-tRNAPhe, 16S RNA contacts with essentially the same proteins (S4, S5, S7, S8, S9/S11, S10, S15, S16 and S17) and in the same ratio, evidencing similar conformation of 30S subunit in these two complexes. In the third complex deacylated tRNAPhe contacts with proteins S4, S5, S6, S8, S9/S11 and S15, 16S RNA-protein interaction differs from those in the first two complexes by a remarkable decrease of cross-linked proteins S8, and S9/S11 and by the appearance of a large amount of cross-linked proteins(s) S13/S14. Hence, this complex differs from the first two by conformation of 30S subunit and, probably, by disposition and/or conformation of tRNA. PMID- 2582235 TI - [The great interest in small RNA]. AB - A review of data concerned with studies on low molecular weight RNA, a rapidly developing field of molecular biology and bioorganic chemistry, is given. The analytical approach allowed to estimate the initial steps of establishment of the problem, to determine the geographical distribution of these studies at present, to reveal the main laboratories involved and to give prognosis on future development. PMID- 2582236 TI - Low level of cellular protein phosphorylation by nontransforming overproduced p60c-src. AB - We have previously found that Rous sarcoma virus variants in which the viral src (v-src) gene is replaced by the cellular src (c-src) gene have no transforming activity. In this study, we analyzed the basis for the inability of the p60c-src overproduced by these variants to transform cells. Phosphorylations of tyrosine residues in total cell protein or in cellular 34K protein are known to be markedly enhanced upon infection with wild-type Rous sarcoma virus. We found that these tyrosine phosphorylations were only slightly increased in the c-src containing virus-infected cells, whereas both levels were significantly increased by infection with wild-type Rous sarcoma virus, or transforming mutant viruses which are derived from c-src-containing viruses by spontaneous mutation. Phosphorylation at tyrosine 416 of p60 itself was also extremely low in overproduced p60c-src and high in p60s of transforming mutant viruses. In immunoprecipitates with monoclonal antibody, the overproduced p60c-src had much lower casein tyrosine kinase activity than did p60v-src. We previously showed that p60 myristylation and plasma membrane localization may be required for cell transformation. p60c-src was similar to transforming p60s in these properties. These results strongly suggest that the low level of tyrosine phosphorylation by overproduced p60c-src accounts for its inability to transform cells. PMID- 2582237 TI - Overexpressed pp60c-src can induce focus formation without complete transformation of NIH 3T3 cells. AB - NIH 3T3 cells were transfected with plasmids containing Moloney murine leukemia virus long terminal repeats and either chicken c-src or v-src genes. In contrast with the effects observed after transfection with plasmids containing c-src and avian retrovirus or simian virus 40 promoter-enhancers (H. Hanafusa, H. Iba, T. Takeya, and F. R. Cross, p. 1-8, in G. F. Vande Woude, A. J. Levine, W. C. Topp, and J. D. Watson, ed., Cancer Cells, vol. 2, 1984; H. Iba, T. Takeya, F. R. Cross, T. Hanafusa, and H. Hanafusa, Proc. Natl. Acad. Sci. U.S.A. 81:4424-4428, 1984; R. C. Parker, R. Swanstrom, H. E. Varmus, and J. M. Bishop, p. 19-26, in G. F. Vande Woude et al., ed., Cancer Cells, vol. 2, 1984; R. C. Parker, H. E. Varmus, and J. M. Bishop, Cell 37:131-139, 1984; D. Shalloway, P. M. Coussens, and P. Yaciuk, p. 9-17, in G. F. Vande Woude et al., ed., Cancer Cells, vol. 2, 1984; D. Shalloway, P. M. Coussens, and P. Yaciuk, Proc. Natl. Acad. Sci. U.S.A. 81:7071-7075; and K. C. Wilhelmsen, W. G. Tarpley, and H. M. Temin, p. 303-308, in G. F. Vande Woude et al., ed., Cancer Cells, vol. 2, 1984), we found that both types of Moloney murine leukemia virus long terminal repeat-src expression plasmids induced focus formation, although c-src induced only 1% as many foci as v-src. The focus-selected c-src overexpressed cells had altered morphology and limited growth in soft agarose but were not tumorigenic in vivo. Cleveland digests, comparative in vitro kinase assays, secondary transfections, and immunoprecipitations indicated that focus formation was caused by rare transfection events that resulted in very high-level pp60c-src expression rather than by mutations of the transfected c-src genes. These results suggest that pp60v-src induced transformation is not a completely spurious activity which is unrelated to the function of pp60c-src but that it represents a perturbation of already existent molecular control processes involving pp60c-src. PMID- 2582238 TI - Human cellular src gene: nucleotide sequence and derived amino acid sequence of the region coding for the carboxy-terminal two-thirds of pp60c-src. AB - The nucleotide sequence of the 3' two-thirds of a highly conserved, molecularly cloned human cellular src gene (c-src) has been determined. This region of the c src gene encodes the tyrosine kinase domain of the cellular src protein (pp60c src) and corresponds to exons 6 through 12 of the chicken c-src gene, as well as nucleotides 545 to 1542 of the Rous sarcoma virus src gene (v-src). The human c src sequence is very strongly conserved with respect to both the chicken c-src and the Rous sarcoma virus v-src genes, with nearly 90% nucleotide homology observed in this region. Amino acid sequence conservation in this region is even greater; 98% of the amino acids are conserved between human and chicken c-src. Furthermore, the exon sizes and the locations of the exon-intron boundaries are identical in the human and chicken c-src genes. However, sequences within the introns have not been conserved, and the introns within the human c-src gene are significantly larger than the corresponding introns within the chicken c-src gene. The strong amino acid conservation between the carboxy-terminal two-thirds of pp60c-src of species as divergent as humans and chickens suggests that this portion of the pp60c-src protein specifies one or more functional domains that are of great importance to some aspect of normal cellular growth or differentiation. PMID- 2582239 TI - Synthesis of U1 RNA in isolated nuclei from sea urchin embryos: U1 RNA is initiated at the first nucleotide of the RNA. AB - Nuclei from sea urchin blastula embryos synthesize a variety of small RNAs, one of which has identical mobility with sea urchin U1 RNA. This RNA is synthesized by RNA polymerase II and, in a hybridization-selection experiment, was selected by the cloned sea urchin U1 gene. The U1 RNA was initiated with ATP, but not GTP, in isolated nuclei with beta-S- and gamma-S-ribonucleotide triphosphates as substrates. The U1 RNA containing thiophosphate at the 5' end was not capped but accumulated as an uncapped transcript from which the thiophosphate could be removed with calf intestinal phosphatase. PMID- 2582240 TI - DNA primase-DNA polymerase alpha from simian cells: sequence specificity of initiation sites on simian virus 40 DNA. AB - Unique single-stranded regions of simian virus 40 DNA, phage M13 virion DNA, and several homopolymers were used as templates for the synthesis of (p)ppRNA-DNA chains by CV-1 cell DNA primase-DNA polymerase alpha. Intact RNA primers, specifically labeled with an RNA capping enzyme, were typically 6 to 8 ribonucleotides long, although their lengths ranged from 1 to 9 bases. The fraction of intact RNA primers 1 to 4 ribonucleotides long was 14 to 73%, depending on the template used. RNA primer length varied among primers initiated at the same nucleotide, as well as with primers initiated at different sites. Thus, the size of an RNA primer depended on template sequence. Initiation sites were identified by mapping 5' ends of nascent RNA-DNA chains on the template sequence, identifying the 5'-terminal ribonucleotide, and partially sequencing one RNA primer. A total of 56 initiation events were identified on simian virus 40 DNA, an average of 1 every 16 bases. Some sites were preferred over others. A consensus sequence for initiation sites consisted of either 3'-dCTTT or 3'-dCCC centered within 7 to 25 pyrimidine-rich residues; the 5' ends of RNA primers were complementary to the dT or dC. High ATP/GTP ratios promoted initiation of RNA primer synthesis at 3'-dCTTT sites, whereas low ATP/GTP ratios promoted initiation at 3'-dCCC sites. Similarly, polydeoxythymidylic acid and polydeoxycytidylic acid were the only effective homopolymer templates. Thus, both template sequence and ribonucleoside triphosphate concentrations determine which initiation sites are used by DNA primase-DNA polymerase alpha. Remarkably, initiation sites selected in vitro were strikingly different from initiation sites selected during simian virus 40 DNA replication in vivo. PMID- 2582241 TI - Nonrandom integration of human U4 RNA pseudogenes. AB - Four loci for human U4 RNA have been characterized by DNA sequence analysis. The results show that all four loci represent pseudogenes, which are flanked by direct repeats. Three of the pseudogenes, designated U4/5, U4/6, and U4/8, have very similar structures; they are all truncated and contain the first 67 to 68 nucleotides of the U4 RNA sequence. Their properties suggest that they were created by integration of truncated cDNA copies of the U4 RNA into new chromosomal sites. An interesting observation was that their flanking regions exhibit sequence homology. A purine-rich 5'-flanking sequence 12 to 13 nucleotides long is almost perfectly conserved in all three loci. Boxes of homology were also found on the 3' side when the U4/6 and U4/8 loci were compared. The U4/4 locus has a slightly different structure; the pseudogene matches the first 79 nucleotides of U4 RNA, but contains a greater number of mutations than the other pseudogenes. Taken together, the results suggest that a frequently occurring type of pseudogene for human U4 was created by a RNA mediated mechanism and that the integration sites have features in common. PMID- 2582242 TI - Activation of hemolytic complement by mouse monoclonal IgG1 antibody: comparison with rabbit IgG. AB - We investigated the ability of a mouse anti-hapten monoclonal IgG1 antibody (Ab) to bind to cell-bound specific hapten and to fix and activate C1 and thus the lytic sequence of complement (C). In a comparative study with polyclonal rabbit anti-hapten IgG Ab, we found that about 6 times more monoclonal Ab molecules than polyclonal were necessary for the generation of 1 hemolytic site/cell: the data were interpreted to mean that a cluster of four cell-bound monoclonal Ab molecules was necessary to bind C1 and activate C-mediated hemolysis. Experiments performed under conditions of low density of cell-bound hapten and excess of antibody showed that both monoclonal and polyclonal IgG Abs were able to react only with 20-30% of the cell-bound hapten and that both Abs recognized the same hapten specificity. We also found that even though monoclonal IgG1 Ab was able to bind strongly to a protein A-Sepharose column and could be eluted only by a low pH buffer, the purified Ab, when bound to cell surface hapten, showed a weak ability to react with free protein A. PMID- 2582243 TI - Glycoprotein PAS-0 from the milk fat globule membrane carries antigenic determinants for epithelial membrane antigen. AB - Epithelial membrane antigen (EMA) can be found in human tissues using antisera raised against defatted human cream. PAS-0 is a glycoprotein which has been extracted from human milk fat globule membranes. Using a polyclonal antiserum and a series of monoclonal antibodies, we have shown that the major antigenic determinant for EMA is carried by PAS-0. A more detailed comparison of the two glycoproteins has been made by establishing a set of radioimmunoassays using the different antibodies. PMID- 2582244 TI - Monoclonal antibodies to human growth hormone can distinguish between pituitary and genetically engineered forms. AB - Monoclonal antibodies (MABs) prepared against human pituitary growth hormone (hGH) have been compared for their binding to pituitary-derived and genetically engineered methionyl growth hormone (met-hGH). The antibodies bind to four non overlapping epitopes of which two are completely shared with human choronic somatomammotropin (hCS). The determinant defined by MAB NA27 was expressed on met hGH to a lesser degree than on hGH of pituitary origin. However, another antibody, QA68, which binds to a determinant closely related to NA27, failed to discriminate between hGH and met-hGH. A further two MABs (EB1 and NA71) were similarly ineffective in distinguishing between the two forms of the hormone. The determinant recognized by antibody EB2 was equally represented on hGH and met-hGH when assessed by a liquid-phase radioimmunoassay: however, measurement of the binding in a solid-phase assay resulted in a two-four-fold lower binding to met hGH. Bioactivity assessed by both an in vitro cell proliferation assay and an in vivo cartilage sulphation bioassay failed to distinguish between the two hormones. It is therefore concluded that the NH2-terminal methionine on bacterially derived growth hormone results in altered antigenicity of the hormone without any measurable effect on bioactivity. PMID- 2582245 TI - Characterization of two epitopes on insulin using monoclonal antibodies. AB - Three monoclonal antibodies (MAb), 21 (IgG1), I10 (IgG1) and H38 (IgG2b), to insulin have been tested for cross-reactivity with 11 species variants of insulin and three of proinsulin. Correlations of differences of reactivities between the MAb and the species variants of insulin with the respective amino acid sequences of the latter have permitted the identification of two epitopes recognized by the MAb which encompass the regions in the A- and B-chains of insulin subject to frequent evolutionary amino acid substitutions. MAb 21 and H38 are directed to an epitope which includes residues B27-30 and A1 or A4 and can discriminate between human and pig insulins which differ only at B30. MAb 21 reacts with human (B30 thr) but not with pig (B30 ala) insulins, whereas MAb H38 exhibits a reciprocal specificity. Neither MAb 21 nor MAb H38 react with human or pig proinsulins respectively indicating that the presence of the C-peptide joining A1 to B30 masks the epitope. MAb 21 reacts with human insulin 125I-labeled at tyr A14 but not B26 suggesting that incorporation of the I atom at B26 also masks the epitope. MAb I10 is directed to an epitope which includes A8-10 and A4 or B3 with a specificity for the human A8-10 sequence. MAb I10 reacts with human proinsulin and human insulin 125I-labeled at either tyr A14 or B26. PMID- 2582246 TI - The circular dichroism of phosphocholine-specific mouse hybridoma and myeloma proteins: unusual properties of the hybridoma protein 101.6G6. AB - The circular dichroism (CD) spectra of five myeloma and six hybridoma proteins specific for phosphocholine were measured in the 250-310-nm range. The effect on the CD spectra of adding phosphocholine was also examined. The five myeloma proteins all had distinctive native spectra and, except for M603 and W3207, unique changes occurred on ligand binding. The hybridomas were chosen as pairs from each of the three known families of phosphocholine-specific immunoglobulins. Those from the T15 or M603 families resembled the appropriate prototype. However, the proteins from the M167 family were all distinctively different in their CD properties. In particular, the hybridoma protein 101.6G6 showed large CD changes on hapten binding and values for the association constant for phosphocholine of 1.1 X 10(5) M-1 and of 5.8 X 10(2) M-1 for acetylcholine were obtained by CD spectrophotometric titration. The CD properties of the proteins are interpreted in the light of the sequence data so far available, including the possible role of the D-segment. PMID- 2582247 TI - Immunochemical studies of tobacco mosaic virus--VI. Attempts to localize viral epitopes with monoclonal antibodies. AB - The specificity of 18 monoclonal antibodies directed to tobacco mosaic virus (TMV) was studied by measuring their ability to bind to viral mutants, to other tobamoviruses, to dissociated viral subunits and to peptide fragments of the viral coat protein. The apparent binding specificity of the antibodies was dependent on the type of enzyme-linked immunosorbent assay used, probably because the antigens were disrupted or denatured when attached to the plastic surface of microtiter wells. The capacity of different monoclonal antibodies to detect single substitutions in the viral coat protein was used to delineate some of the topographic epitopes of TMV. By means of computer-generated images of the surface residues of the viral subunit, it was possible to identify certain clusters of residues involved in binding to some of the monoclonal antibodies. The results clearly illustrate the operational limitations encountered when monoclonal antibodies are used for elucidating the antigenic structure of proteins. PMID- 2582248 TI - [Mechanism of glucan-induced aggregation of Streptococcus mutans]. PMID- 2582249 TI - Some factors affecting optimal differential staining of sister-chromatids in vivo in the fish Nothobranchius rachowi. AB - In the past few years, routine studies of SCE induction in vivo in fish have been hampered by unreliable SCD techniques. This paper presents a number of modifications of the SCD technique in vivo in Nothobranchius rachowi. Major improvements were obtained by BrdU incorporation from aqueous solutions, short intervals between preparation and staining of slides and post-treatment with HCl. These improvements resulted in a highly reliable SCD procedure in Nothobranchius with a low level base-line SCE frequency (0.90 SCE/metaphase, 0.059 SCE/chromosome). Further research is now directed at gathering additional data on base-line SCE frequencies, establishing the sensitivity of the assay for aqueous solutions of known mutagens, and defining an experimental set-up for optimal statistical evaluation. PMID- 2582250 TI - An alteration leading to loss of ability to support phleomycin mutagenesis in the pKM101-derived plasmid pGW16 is located in or close to the mucAB genes. AB - The differences between the plasmid pKM101 and its derivative pGW16, which has lost the ability to support muc-dependent phleomycin mutagenesis, while retaining other muc-dependent phenotypes, have been further investigated. Deletion derivatives which retain only 10.8 kb (approximately one third) of the pKM101 genome but retain the muc genes have been constructed from both pKM101 and pGW16. The deletion derivatives confer protection and mutagenesis-enhancing properties similar to those of their respective parents, indicating that the lesion in the mutant plasmid pGW16 lies in or close to the muc genes. Differences in the muc dependent phenotypes of strains containing pKM101 or pGW16 suggest that the pGW16 lesion results in either differential loss of function in the muc gene products, or constitutive expression of the muc gene products. PMID- 2582251 TI - Reactivation and mutagenesis of herpes virus in 5-azacytidine-treated monkey kidney cells. AB - Enhanced survival of UV-damaged herpes simplex virus and Simian virus 40 was investigated in CV-1 monkey cells treated with inhibitors of DNA methylation such as 5-azacytidine and ethionine. Survival of UV-irradiated virus was higher in treated cells than in untreated cells. Survival of herpes virus irradiated with 60Co gamma-ray was not enhanced in the treated cells. The frequency of forward mutation of herpes virus increased in 5-azacytidine-treated cells. Relative content of methylcytosine was reduced in the cells treated with 5-azacytidine. Therefore a mechanism similar to UV-enhanced reactivation of virus was operating in the cells with hypomethylated DNA. PMID- 2582253 TI - Systemic lupus erythematosus with deficiency of the T4 epitope on T helper/inducer cells. AB - Three black Jamaicans with systemic lupus erythematosus (SLE) were identified whose T helper/inducer cells lacked the T4 epitope (T4 epitope-deficient phenotype). All three patients had lymphadenopathy as part of their syndromes. The asymptomatic and otherwise healthy T4 epitope-deficient brother of one of these patients also had lymphadenopathy in a distribution identical to that of his sister with SLE. Family studies pointed to an autosomal codominant mode of inheritance not linked to the HLA locus for the T4 epitope phenotype. Cultures of peripheral-blood mononuclear cells revealed impaired B-cell differentiation upon stimulation with pokeweed mitogen in cells originating from the T4 epitope deficient family members as compared with those originating from their T4 epitope intermediate relatives. Ratios of T helper/inducer cells to T suppressor/cytotoxic cells, the presence of various autoantibodies, and proliferation in response to mitogens and in the mixed lymphocyte reactions did not correlate with T4 epitope phenotype. We suggest that SLE in association with the T4 epitope-deficient phenotype may represent a unique subset of patients with SLE that has distinct clinical and immunologic properties. PMID- 2582252 TI - Correspondence between effects of 5-azacytidine on SCE formation, cell cycling and DNA methylation in Chinese hamster cells. AB - The effects of 5-azacytidine (5-Aza-C), alone and in combination with mitomycin C, were measured on sister-chromatid exchange (SCE) formation and DNA methylation in different genomic regions of Chinese hamster ovary cells and in Chinese hamster cells containing amplified, dihydrofolate reductase sequences and resistant to methotrexate. 5-Aza-C, when present for the penultimate preharvest cell cycle, induced SCEs in a manner consistent with a directly measured reduction in deoxycytosine methylation in cellular DNA. At higher 5-Aza-C concentrations, cell cycling was inhibited and both SCE induction and DNA demethylation tended to level off. Under appropriate conditions, 5-Aza-C also potentiated the induction of SCEs by mitomycin C. 5-Aza-C-induced DNA demethylation could also be detected in the vicinity of different DNA sequences with the use of comparative HpaII/MspI digestion, DNA blotting, and molecular probes. The efficiency of an individual demethylation event in inducing SCE induction appeared to be very low, compared with alkylating agents such as 8 methoxypsoralen, suggesting that SCE induction by 5-Aza-C might be an indirect effect from long range changes induced in cellular DNA or chromatin conformation. PMID- 2582254 TI - The molecular basis for genetic deficiency of the second component of human complement. AB - Genetic deficiency of the second component of complement (C2) is the most common complement-deficiency state among Western Europeans and is frequently associated with autoimmune diseases. To examine the molecular basis of this deficiency, we established cultures of blood monocytes from four families with C2-deficient members. Using a hemolytic-plaque assay, [35S]methionine metabolic labeling of proteins in tissue culture and immunoprecipitation, RNA extraction and Northern blot analysis, and DNA restriction-enzyme digestion and Southern blot analysis, we found that C2 deficiency is not due to a major gene deletion or rearrangement but is the result of a specific and selective pretranslational regulatory defect in C2 gene expression. This leads to a lack of detectable C2 mRNA and a lack of synthesis of C2 protein. The approach used in this study should prove useful in examination of other plasma protein deficiencies, especially those in which the deficient gene is normally expressed in peripheral-blood monocytes or tissue macrophages and in which ethical considerations preclude the use of liver or other tissue for study. PMID- 2582255 TI - An analysis of serum samples positive for HTLV-III antibodies. PMID- 2582256 TI - Neurochemical studies of early-onset Alzheimer's disease. Possible influence on treatment. AB - Multiple neurotransmitter deficits found in recent autopsy studies of patients with Alzheimer's disease may militate against the success of "simple cholinergic replacement" as treatment. To study acetylcholine synthesis, we measured the incorporation of radiolabeled glucose into the transmitter in temporal-cortex specimens obtained at diagnostic craniotomy in 17 young patients with Alzheimer's disease. Synthesis of acetylcholine was significantly correlated with cognitive impairment. These results are consistent with the view that the deficit in the presynaptic cholinergic system is a relatively early change in the development of the clinical features of the disease. Other alterations in noradrenergic cells, some cortical neurons, postsynaptic cortical receptors, and possibly serotoninergic cells may not be closely associated with Alzheimer's disease. PMID- 2582257 TI - Inflammatory mediators in late antigen-induced rhinitis. AB - To investigate the mechanisms responsible for the late-phase response in patients with allergies, we measured four biochemical mediators (histamine, tosyl-L arginine methyl ester [TAME]-esterase, kinin, and prostaglandin D2) in nasal secretions after nasal challenge with pollen antigen in 12 patients with allergy. Nine patients had an immediate response and a recurrence of symptoms 3 to 11 hours after challenge. The clinical symptoms during recurrence were accompanied by a second increase in levels of histamine, TAME--esterase, and kinin over base line values, although kinin levels were lower than during the immediate response. In contrast, although the levels of prostaglandin D2 were significantly increased during the immediate response, they did not increase above base line during the late response. Rechallenge with allergen 11 hours after the initial provocation, however, was associated with reappearance of all four biochemical mediators, including prostaglandin D2. We conclude that the late response to nasal challenge with allergen is accompanied by a second increase in the concentrations of histamine and TAME--esterase but differs from the immediate response in the lack of prostaglandin D2 production and in the amount of kinin generated. Since histamine is released only by mast cells and basophils and prostaglandin D2 is not produced by basophils, we suggest that these cells are partly responsible for the late-phase response. PMID- 2582258 TI - Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. Evidence for a selective defect in soluble antigen recognition. AB - We studied purified subpopulations of lymphocytes from patients with the acquired immunodeficiency syndrome (AIDS) in order to determine whether intrinsic defects in lymphocyte function, aside from those due to alterations in lymphocyte numbers, were present. Mitogen-stimulated DNA synthesis, production of gamma interferon, production of interleukin-2, and expression of interleukin-2 receptors, although variably decreased in unseparated cell populations, were normal in populations of purified T-cell subsets. In contrast, DNA synthesis in response to the soluble protein antigen tetanus toxoid was decreased in both unseparated and purified T-cell subpopulations. Cell-mixing experiments demonstrated that the hyporesponsiveness of the unfractionated lymphocytes from patients with AIDS was not due to active suppression. We conclude that the lymphocytes of patients with AIDS, although capable of undergoing a normal degree of blast transformation and lymphokine production after mitogenic stimulation, have an intrinsic defect in their ability to recognize and respond to soluble antigen. PMID- 2582259 TI - The treatment of cancer pain. AB - Pain is one of the most feared consequences of cancer. Control of pain from cancer should be possible with the approaches discussed above. Changing attitudes toward the effective use of narcotic analgesics, the development of novel routes and methods of administration, and a clinical approach based on scientific principles and humane care offer the promise of improved management of pain in patients with cancer. PMID- 2582261 TI - Cell motility. Fast axonal transport dissected. PMID- 2582260 TI - ATP ase-positive and metallophilic cells in the skin of frog, Rana catesbeiana. PMID- 2582262 TI - Neurophysiology. Potential challenge from glia. PMID- 2582263 TI - Voltage-dependent potassium currents in cultured astrocytes. AB - Astrocytes are a major cell type in the mammalian central nervous system (CNS), yet their functions remain uncertain. There are two principal classes of these glial cells--protoplasmic astrocytes, found mainly in grey matter, and fibrous astrocytes, which occur mainly in white matter. Recently, these two types of astrocytes have been distinguished in cultures of developing CNS and have been shown to be biochemically distinct. Because both types contain large numbers of glial filaments in vitro and hence appear 'fibrous', we will refer to them as type 1 (protoplasmic) and type 2 (fibrous) astrocytes. Most type 2 astrocytes in culture share several properties with neurones; for example, they have a process bearing morphology and bind tetanus toxin and the monoclonal antibody A2B5, both of which recognize specific gangliosides and were initially considered to be neurone-specific markers in the CNS. We have therefore investigated whether type 2 astrocytes also share electrophysiological properties with neurones. Using intracellular microelectrode and 'whole-cell' (patch-clamp) recording techniques, we have now found that both type 1 and type 2 astrocytes in culture have time- and voltage-dependent potassium ion conductances which, until recently, were considered to be confined largely to electrically excitable cells. PMID- 2582264 TI - Translocation of vesicles from squid axoplasm on flagellar microtubules. AB - Directed intracellular particle movement is a fundamental process characteristic of all cells. During fast axonal transport, membranous organelles move at rapid rates, from 1 to 5 micron s-1, in either the orthograde or retrograde direction along the neurone and can traverse distances as long as 1 m (for reviews, see refs 1-3). Recent studies indicate that this extreme example of intracellular motility can occur along single microtubules, but the molecules generating the motile force have not been identified or localized. It is not known whether the force-transducing 'motor' is associated with the moving particle or with the microtubule lattice. To distinguish between these hypotheses and to characterize the membrane-cytoskeletal interactions that occur during vesicle translocations, we have developed a reconstituted model for microtubule-based motility. We isolated axoplasmic vesicles from the giant axon of the squid Loligo pealei as described previously. The vesicles (35-475 nm in diameter) were then added to axonemes of Arbacia punctulata spermatozoa that served as a source of microtubules. Axonemes were used because the tubulin subunit lattice of the A subfibre of a given outer doublet is the same as the subunit lattice of neuronal microtubules along which motility occurs. Moreover, all the microtubules of a single axoneme show the same structural polarity, indicating that the axoneme represents an oriented microtubule substrate. Here we demonstrate that vesicle motility is ATP-dependent, that it is not mediated by the flagellar force transducing molecule dynein and that the direction of movement is not specified by microtubule polarity. PMID- 2582265 TI - Developmental acquisition of Ca2+-sensitivity by K+ channels in spinal neurones. AB - A developmental change in the ionic basis of the inward current of action potentials has been observed in many excitable cells. In cultured spinal neurones of Xenopus, the timing of the development of the action parallels that seen in vivo. In vitro, as in vivo, neurones initially produce action potentials of long duration which are principally Ca-dependent; after 1 day of development the impulse is brief and primarily Na-dependent. At both ages, however, both inward components are present and the mechanism underlying shortening of the action potential is unknown. One possibility is that the outward currents change during development. Using the patch-clamp technique, we have recorded single K+-channel currents in membrane patches isolated from the cell bodies of cultured embryonic neurones. The unitary conductance of one class of K+ channels was approximately 155 pS and depolarization increased the probability of a channel being open. Neither conductance nor voltage dependence seemed to change with time in culture; in contrast, the Ca2+-sensitivity of this K+ channel increased. In younger neurones, Ca2+-sensitivity was greatly reduced or absent, whereas in more mature neurones, the activity of this channel was Ca-dependent. Such a change could account for the shortening of the action potential duration by increasing the relative contribution of outward currents. PMID- 2582266 TI - Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. AB - B-cell stimulatory factor-1 (BSF-1), formerly designated B-cell growth factor, is a T-cell-derived factor required for entry into the S phase of the cell cycle by B cells stimulated with low concentrations of anti-IgM antibodies. BSF-1 acts directly on resting B cells to prepare them to synthesize DNA more promptly on subsequent exposure to competent stimuli and to strikingly enhance their expression of class II molecules of the major histocompatibility complex. Previous studies have shown that murine BSF-1 can be separated physically from interleukin-2 (IL-2) and that the molecule has an apparent relative molecular mass (Mr) of approximately 15,000 and pI values of 6.4-6.7 and 7.4. Here, we report the production of a monoclonal antibody to BSF-1, its use in characterizing BSF-1, and functional studies demonstrating that this molecule is distinct from IL-1, IL-2 and IL-3. PMID- 2582267 TI - Imunovir. PMID- 2582269 TI - Modulation of some deadly sins. PMID- 2582268 TI - Identical V beta T-cell receptor genes used in alloreactive cytotoxic and antigen plus I-A specific helper T cells. AB - T lymphocytes involved in the cellular immune response carry cell-surface receptors responsible for antigen and self recognition. This T-cell receptor molecule is a heterodimeric protein consisting of disulphide-linked alpha- and beta-chains with variable (V) and constant (C) regions. Several complementary DNA and genomic DNA clones have been isolated and characterized. These analyses showed that the genomic arrangement and rearrangement of T-cell receptor genes using VT, diversity (DT), joining (JT) and CT gene segments is very similar to the structure of the known immunoglobulin genes. We have isolated two cDNA clones from an allospecific cytotoxic T cell, one of which shows a productive V beta-J beta-C beta 1 rearrangement without an intervening D beta segment. This V beta gene segment is identical to the V beta gene expressed in a helper T-cell clone specific for chicken red blood cells and H-21. The other clone carries the C beta 2 gene of the T-cell receptor, but the C beta 2 sequence is preceded by a DNA sequence that does not show any similarity to V beta or J beta sequences. PMID- 2582270 TI - Substance P raises neuronal membrane excitability by reducing inward rectification. AB - Much interest has recently centred on the properties of peptides that modulate the excitability of nerve cells. Such compounds include the undecapeptide substance P, which is particularly well established as an excitatory neurotransmitter, and we examine here its effects on magnocellular cholinergic neurones taken from the medial and ventral aspects of the globus pallidus of newborn rats and grown in dissociated culture. These neurones have previously been shown to respond to substance P3 and are analogous to the nucleus basalis of Meynert in man, which gives a diffuse projection to the cerebral cortex and whose degeneration is the likely cause of Alzheimer's disease. Substance P depolarizes these cultured neurones by reducing an inwardly rectifying potassium conductances; this conductance has been found in several neuronal types and has similar properties to those of certain other cells. As discussed below, modulation of inward (or anomalous) rectification by substance P implies a self reinforcing element to the depolarization caused by the peptide. PMID- 2582271 TI - Modulation of a transient outward current in serotonergic neurones by alpha 1 adrenoceptors. AB - The excitability of various neurones in the mammalian central nervous system (CNS), ranging from motoneurones to serotonergic neurones, is enhanced by alpha 1 adrenoceptor agonists. Excitations mediated via alpha 1-adrenoceptors are associated with a slow depolarization and an increase in input resistance, probably resulting from a decrease in resting potassium conductance. However, the involvement of voltage-dependent transient currents in mediating alpha 1 excitatory effects has not been evaluated. An early transient outward current has been described which is important in regulating the frequency of repetitive firing; it is activated by depolarizing voltage steps from potentials more negative than rest and blocked by 4-aminopyridine. This current, which has been termed 'IA', was found originally in invertebrates and subsequently in various vertebrate neurones. The present single-electrode voltage-clamp study demonstrates an early transient outward current (IA) in serotonergic neurones which is suppressed by noradrenaline and the alpha 1-agonist phenylephrine; a suppression of IA may account in part for the acceleration of pacemaker activity induced by alpha 1-agonists in serotonergic neurones. PMID- 2582272 TI - Modulation of single Ca2+-dependent K+-channel activity by protein phosphorylation. AB - There is considerable evidence that cyclic AMP can modulate the electrical activity of excitable cells and that protein phosphorylation by the catalytic subunit (CS) of cAMP-dependent protein kinase is a necessary step in these modulatory effects. In analogy to alterations in enzyme activities following phosphorylation, it seems possible that direct phosphorylation of ion-channel proteins may alter their gating properties, giving rise to the observe changes in electrical activity. However, the results obtained so far do not indicate whether it is ion channels themselves that are phosphorylated, or whether phosphorylation is simply an early step in some cascade of events which leads ultimately to modulation of channel activity. The development of single-channel recording techniques has provided a way to investigate this question. Here we describe effects of CS on the activity of individual CA2+-dependent K+ channels from the nervous system of the land snail Helix measured in isolated membrane patches and in artificial phospholipid bilayers. The results demonstrate that cAMP-dependent protein phosphorylation produces long-lasting changes in the activity of individual channels, and indicate that the relevant phosphorylation site is closely associated with the channel. PMID- 2582273 TI - Drastic change in idiotypic but not antigen-binding specificity of an antibody by a single amino-acid substitution. AB - In proliferating B lymphocytes, somatic mutation of rearranged antibody variable (V)-region genes occurs at high frequency and may have a key role in the selection of these cells. It is of interest in this context to learn in which way single mutations can affect antigen binding and/or idiotypic specificity of an antibody. Previous investigations have analysed spontaneous mutants of myeloma and hybridoma cells in which the mutation affected the antigen-binding specificity of the antibody. Here we describe an antibody mutant that has fully retained antigen-binding specificity but has lost or drastically changed all V region antigenic determinants (idiotopes) of the wild type as defined by monoclonal anti-idiotope antibodies. The mutant phenotype is generated by a glycine to arginine exchange in the middle of the diversity (D) element, at position 103 of the heavy chain. PMID- 2582274 TI - Tissue localization and chromosomal assignment of a serum protein that tracks the cystic fibrosis gene. AB - The basic gene defect in the autosomal recessive disorder cystic fibrosis has not been identified, and no firm linkage of the disorder to any other marker has been reported. However, a serum protein abnormality present in unaffected heterozygotes as well as in affected homozygotes has been described, and immunological quantitation of this protein, termed cystic fibrosis antigen, allows the three genotypes to be distinguished. We show here that an immunologically indistinguishable protein is present at high concentrations in granulocytes from normal and cystic fibrosis individuals as well as in myeloid leukaemia cells. Somatic cell hybrids between the mouse myeloid stem-cell line WEHI-TG and myeloid leukaemia cells express cystic fibrosis antigen only when human chromosome I is present. PMID- 2582276 TI - Study of the contractile effect of 5-hydroxytryptamine (5-HT) in the isolated longitudinal muscle strip from guinea-pig ileum. Evidence for two distinct release mechanisms. AB - The contractile effect of 5-HT in the isolated longitudinal ileal muscle of adult guinea-pigs was studied over a large concentration range. 5-HT produced a biphasic concentration-response curve indicative of an interaction with at least two independent populations of receptors. The concentrations which elicited half maximal effects for the first and the second phases of the concentration-response curve were estimated as 1.5 +/- 1.2 X 10(-8) mol/l and 1.3 +/- 0.4 X 10(-6) mol/l respectively. The maximal response produced by the interaction of 5-HT with the high affinity receptor (i.e. first phase) was calculated as 27 +/- 9.3% of the total response. The biphasic concentration-response was not influenced by methysergide (10(-6) mol/l). The effect of low concentrations of 5-HT (less than 3 X 10(-7) mol/l) was antagonised by atropine (10(-7) mol/l), tetrodotoxin (TTX) (10(-6) mol/l), morphine (10(-5) mol/l), the substance P antagonist, D-Pro4,D Trp7,9-SP4-11 (3 X 10(-5) mol/l) and capsaicin (10(-5) mol/l). Physostigmine (10( 7) mol/l) augmented the effect. The response to high concentrations of 5-HT (3 X 10(-7)-3 X 10(-6) mol/l) was antagonised by ICS 205-930 and D-Pro4,D-Trp7,9-SP4 11 in a competitive manner and was inhibited by TTX, morphine and capsaicin in an insurmountable way. The effect of very high concentrations of 5-HT (greater than 10(-5) mol/l) could be partially antagonised by methysergide (10(-7) mol/l) in the presence of ICS 205-930 (10(-7) mol/l) and totally by a combination of methysergide and TTX.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582275 TI - On the mechanism of catecholamine-induced hyperpolarization of skeletal muscle cells. AB - Catecholamines (noradrenaline, adrenaline and isoprenaline) were tested for their effect on the resting membrane potential of mouse skeletal muscle cells. In freshly isolated muscles incubated in the normal solution containing 5 mol . l-1, catecholamines increased the resting membrane potential (RMP) by 3-5 mV. In Na+ loaded muscles incubated in a K+-free solution, however, catecholamines increased the RMP by 13-16 mV; consequent application of K+ to these muscles did not hyperpolarize the membrane further. A significant decrease of input membrane resistance was observed during the noradrenaline-induced hyperpolarization. This indicates that the passive membrane permeability for K+ ions was apparently increased. Noradrenaline-induced hyperpolarization requires the presence of calcium ions in the incubation solution. We therefore assume that catecholamines hyperpolarize the membrane by Ca2+-dependent K+-channels activation. The action of catecholamines on the resting membrane potential of skeletal muscle exhibits a 50% nonspecific effect as far as the adrenergic receptor is concerned, and the rest may be blocked by adrenergic blocking agents. PMID- 2582277 TI - Effect of triamterene on 5-hydroxytryptamine biosynthesis in different brain areas. AB - Triamterene is structurally similar to the natural cofactor of tryptophan hydroxylase, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin. The hydroxylation of tryptophan has been studied by measuring the accumulation of 5-hydroxytryptophan (5-HTP) and the concentrations of 5-hydroxytryptamine (5-HT) and 5 hydroxyindoleacetic acid (5-HIAA) in brainstem, frontal cortex and hypothalamus after inhibition of L-amino acid decarboxylase with benserazide hydrochloride and administration of either the vehicle or triamterene. Triamterene (30 mg/kg i.p.) decreased 5-HTP accumulation and 5-HT concentrations in brainstem and hypothalamus after 90 min; when the diuretic was given p.o. either acutely or chronically (triamterene 30 mg/kg twice daily during 4 days), no effect either on 5-HTP accumulation or on 5-HT and 5-HIAA concentrations was observed in the three brain areas studied. These results are in accordance with the 4 to 5 times higher concentrations of triamterene plus metabolites found in brainstem and hypothalamus after the acute i.p. administration of the drug than after an acute or chronic p.o. treatment. Hence, the effect of triamterene on 5-HT biosynthesis depends on the concentration it reaches in each brain area after i.p. or p.o. administration. PMID- 2582278 TI - Substance P action on phosphoinositides in guinea-pig intestinal muscle: a possible transduction mechanism? AB - The effect of substance P on the metabolism of membrane phosphoinositides and the possible role of this effect in the contractile response to substance P was investigated in longitudinal muscle strips obtained from the guinea-pig small intestine and prelabelled with [3H] inositol. Substance P (2.2 microM) failed to change significantly the tissue content of phosphoinositides but caused an accumulation of their water-soluble hydrolysis products, inositol bisphosphate (InsP2) and inositol monophosphate (InsP). These experiments were carried out in the presence of Li+ (12 mM), since only under these conditions could an accumulation of InsP2 be observed. The rate at which InsP2 and InsP accumulated was highest during the first 0.5 min of exposure to substance P (2.2 microM) and then decreased rapidly. Thus, the rate of inositol phosphate accumulation paralleled the time course of the contractile response to substance P. The magnitude of inositol phosphate accumulation was related to the concentration of substance P (22 nM-22 microM). The substance P-induced accumulation of InsP2 and InsP was not reduced when muscle strips had been incubated in Ca2+-free medium, for a time period sufficient to deplete the intracellular Ca2+ store which can be released by substance P, or in Ca2+-free medium containing high [K+]. These findings are compatible with the concept that hydrolysis of membrane phosphoinositides is a mechanism that links substance P receptor activation to contraction but further work is needed to establish a causal relationship. PMID- 2582279 TI - Effects of para-substituted beta-adrenoceptor blocking agents and methyl substituted phenoxypropanolamine derivatives on maximum upstroke velocity of action potential in guinea-pig papillary muscles. AB - The effects of atenolol (2-5 mmol/l), sotalol (1-2 mmol/l) and pamatolol (0.1-1 mmol/l), together with N-tertiary butyl phenoxypropanolamines with o-methyl (D 2T: 50-100 mumol/l) m-methyl (D-3T: 50-100 mumol/l) and p-methyl (D-4T: 100-200 mumol/l) group as well as with o,p-methyl groups (D-24T) (50-100 mumol/l) on action potentials (APs) were investigated in isolated guinea-pig papillary muscles. All the drugs in these concentrations produced a concentration-dependent reduction of the maximum upstroke velocity (Vmax). The reduction of Vmax in premature APs induced by stimuli interpolated between the basic driving rate of 0.25, 0.1 or 0.027 Hz decayed exponentially during diastolic intervals. The time constants of these decay processes tau for atenolol, pamatolol and sotalol ranged between 260-541 ms, those for D-3T and D-4T between 655-1,166 ms, and D-2T and D 24T between 1,565-1,931 ms. A drug which provided larger tau values caused the reduction of Vmax in a wider range of the frequency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582280 TI - [Calcium antagonists, calcium entry blockers and calcium overload blockers; nomenclature and classification]. PMID- 2582282 TI - [Effect of liposomes containing antibodies to cyclic nucleotide phosphodiesterase on the receptor potential of rods and cones of the frog retina]. AB - Liposomes loaded with monospecific cGMP-phosphodiesterase (PDE) antibodies act like PDE inhibitors (methylxantins, papaverine) on the aspartate-isolated rod and cone receptor potentials of the isolated perfused rod retina. The response amplitude drastically increases, especially at low stimulus strength, and its time course slows down. Pure lipid liposomes with no antibodies, liposomes loaded with control immunoglobulins, as well as PDE antibodies without liposomes, have no such actions. The effects are readily reversible by wash-out, which implies the liposome + antibodies action without penetrating the cells. The increase in the response amplitude can be only partly explained by the measured increase in the extracellular resistance of the photoreceptor layer under liposome action. It is supposed that the specific adsorption of liposomes on the photoreceptor cell surface changes the function of the intracellular transmission mechanism or (and) the properties of ionic channels of the plasma membrane in yet unknown way. PMID- 2582281 TI - [Effect of blockade of axonal transport on endplate currents of muscle fibers in the frog]. AB - The evoked and spontaneous end-plate currents (EPC) were measured in normal voltage-clamped frog sartorius muscle fibres and after colchicine blockade of axoplasmic transport in the corresponding nerve. Colchicine application decreased the growth rate and increased the decay time constant of EPC without changes in the average amplitude of EPC and miniature EPC, quantum content of EPC and frequency of miniature EPC. The increase in EPC time constant was combined with an increase in the sensitivity of the time constant to holding potential, but there were no changes in the amplitude of EPC as a function of holding potential in the reversal potential of EPC. It is suggested that the increase in the EPC decay time constant was due to the appearance of a new population of receptor- ion channel complexes with opening time similar to that described for extrajunctional receptors after denervation. The neurotrophic control of chemosensitive muscle fibre membrane depended on the axoplasmic flow. PMID- 2582283 TI - Determination of type specific antigenic reactivities and quantitation of murine mammary tumor virus by ELISA. AB - Type specific differences associated with the antigenic determinants of exogenous and endogenous murine mammary tumor viruses (MuMTVs) isolated from strain C3H(Jax) and ICRC were demonstrated by competition enzyme linked immunosorbent assay (ELISA). In this assay, highly purified intact MuMTV from the milk of strain C3H(Jax) was conjugated to the enzyme penicillinase using glutaraldehyde. IgG fraction of antiserum prepared against disrupted C3H (Jax) MuMTV was used in the competition ELISA. The assay was highly reproducible, specific to MuMTV antigens and detected 6-9 ng of the viral proteins. For competition, MuMTV preparations from corresponding endogenous MuMTV carrying subline C3H(Mect) and ICRCf were also used. The assay demonstrated the type specific antigenic reactivities inherent in the MuMTVs isolated from C3H(Jax) and ICRC strains of mice. The competition ELISA was also used to quantitate MuMTV specific proteins in tissue extracts and milk plasma. PMID- 2582284 TI - [Value of visual evoked potentials and cerebrospinal fluid in the clinical diagnosis of multiple sclerosis. A comparative study in the context of anamesis, clinical aspects and computer tomography findings]. PMID- 2582285 TI - Effects of lindane on excitation and inhibition evoked in dentate gyrus by perforant path stimulation. AB - Lindane, 10 mg/kg, IP in DMSO, was administered to rats implanted with electrodes to stimulate the perforant path and record from the dentate gyrus of the hippocampal formation. Dentate responses were examined in acutely prepared, anesthetized rats and chronically prepared rats in unanesthetized and anesthetized states. The most significant and reliable effect of lindane administration was to increase the number of granule cells excited to discharge in response to perforant path stimulation. Further analysis indicated that lindane did not appear to produce this action by increasing transmitter release from the perforant path terminals. The primary site of action was the granule cell itself. Inhibition, mediated by recurrent collaterals and believed to be GABA-mediated, was not reduced and, in some circumstances, was increased after lindane administration. These data suggest that the primary action of lindane in intact subjects is to increase neuronal excitability. Enhanced transmitter release or reduction in GABA-mediated inhibition could not be demonstrated to contribute significantly to this effect. PMID- 2582286 TI - Effects of neonatal chlordecone exposure on pituitary-adrenal function in adult Fischer-344 rats. AB - Fischer-344 rat pups of either sex were injected on day four of age with 1 mg/pup chlordecone (CLD) or DMSO vehicle. At 77-78 days of age, the rats were subjected to a repeated stress-induced analgesia (SIA) paradigm. A white noise (conditioned stimulus; CS) was paired with scrambled footshock for approximately one-half of the rats, while the remaining rats were exposed to the CS only. Conditioning occurred over a seven day period, one trial per day. On day 8 all rats received the CS only; 15 min later, the rats were sacrificed and serum and adrenals collected for corticosterone and/or prolactin measurements. Although prior neonatal exposure to CLD had no effect on the acquisition of the conditioned response or the responsiveness of the adrenocortical system to the CS, basal levels of serum and adrenal corticosterone were generally depressed in CLD exposed males. Basal serum prolactin levels were decreased and increased in CLD exposed males and females, respectively. These data suggest that neonatal CLD exposure may serve as a chemical stressor that produces long-lasting alterations in basal pituitary-adrenocortical function. The expression of these effects also appeared to be sex-dependent. PMID- 2582287 TI - Nucleic acid and protein synthesis inhibition in developing brain by ethanol in the absence of hypothermia. AB - Effects of acute or chronic ethanol administration have been studied on protein, RNA and DNA synthesis in the developing brain in the absence or presence of hypothermia. Acute ethanol was given intraperitoneally (4 g/kg) and for chronic ethanol treatment the pups were allowed to suckle on the ethanol-fed dams. Dams were pair-fed on nutritionally adequate liquid-sustacal diet. Ethanol administration, both acutely and chronically, inhibited the in vivo and in vitro protein synthesis in the absence or presence of hypothermia. This data suggests that ethanol per se is capable of producing the inhibition of protein synthesis in brain without its hypothermic effect. However, the inhibitory effect of ethanol is more pronounced in the presence of ethanol-mediated hypothermia. Hypothermia in itself also causes a decrease in the synthesis of proteins. Maternal ethanol consumption results in a significant decrease in the synthesis of both RNA and DNA in the developing brain of suckling newborn either in the absence or presence of hypothermia. RNA and DNA synthesis was measured by following the incorporation of (5-(3)H) uridine and (14C)thymidine respectively. Decrease in body temperature alone also resulted in decreased RNA and DNA synthesis in the developing brain. Ethanol reaching the suckling newborn from maternal milk resulted in decreased brain weights, total protein, ribosomal protein, total RNA, ribosomal RNA, and total DNA of the brain. Neonatal brain proteolytic and DNA-polymerase activities were inhibited in the ethanol-fed group. An inhibition of proteolytic activity reflects a compensatory mechanism of the developing brain to decrease the breakdown of proteins in response to the inhibitory effect of ethanol on protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582288 TI - A serum factor cross-reactive with antibodies to a determinant of rabbit encephalitogenic sequence 65-74 of myelin basic protein. AB - A serum factor, cross-reactive with antibodies to a defined determinant of myelin basic protein (residues 66-71), has been found in the sera of nine mammalian species where it may function as a specific neuroautotolerogen. In equilibrium competitive inhibition radioimmunoassays the factor appears to be completely competitive with synthetic peptide S24 (TTHYGSLPQKG) at high affinity and is therefore termed MBP-SF-24 (myelin basic protein serum factor of the S24 type). The bulk of the activity can be recovered by ammonium sulfate fractionation at 61.1% saturated ammonium sulfate (SAS), pH 7, (fraction E) after removal by precipitation at pH 7 of the 37.5, 42.6, 47.5, and 51.4% SAS fractions (fractions A-D), including the immunoglobulins, and before removal by precipitation at pH 5 of the albumin fraction (fraction F). The factor, by its retention on XM300 during ultrafiltration of fraction E, can be purified 20-fold from serum proteins without much loss through a combination of SAS fractionation and ultrafiltration. The yield of MBP-SF-S24 in fraction E may range from a low 26 pmol S24 equivalents from 10 ml in sheep serum to a high 1.7 nmoles from 10 ml rat serum. The serum factor is reactive at high affinity with each of two populations of S24 reactive antibodies in one rabbit reagent antiserum and with one of two populations of S24-reactive antibodies in another. It appears to express a determinant involving residues THYGSL (66-71) of myelin basic protein with the same conformation as found in intact S24. PMID- 2582291 TI - [Transcatheter embolization with Ivalon particles in cases of intracranial meningiomas]. PMID- 2582289 TI - Effect of chronic haloperidol and quinacrine coadministration on striatal HVA levels and stereotypic behaviors in response to apomorphine in the rat. AB - The effects of chronic administration of quinacrine, a phospholipase A2 inhibitor, on striatal homovanillic acid (HVA) levels and behavioral sensitivity to challenge with a dopamine agonist were examined in rats. Moreover, the ability of chronic phospholipase A2 inhibition to modulate the behavioral supersensitivity and striatal HVA reduction induced by chronic haloperidol administration was also examined. Daily intraperitoneal injection of quinacrine resulted in a significant reduction of striatal HVA levels. Coadministration of haloperidol with quinacrine in this paradigm caused a more profound reduction of striatal HVA levels than either drug administered alone. That this effect of combined administration is not simply due to postsynaptic effects of quinacrine on dopamine receptor sensitivity is suggested by the fact that behavioral supersensitivity was not induced by quinacrine alone nor was the behavioral supersensitivity induced by the quinacrine-haloperidol combination greater than that induced by chronic haloperidol administration alone. There were no effects of any treatment condition on striatal levels of serotonin (5-HT) or 5 hydroxyindoleacetic acid (5-HIAA). These data implicate phospholipase A2 activity in the regulation of dopaminergic transmission. PMID- 2582290 TI - Generation and characterization of mouse monoclonal antibodies to the myelin associated glycoprotein (MAG). AB - A panel of mouse monoclonal antibodies to rat and human myelin-associated glycoprotein (MAG) was developed. Normal mice were unresponsive to rat MAG, and successful immunization with rat MAG was only achieved in autoimmune NZB mice. By contrast, all strains of mice were responsive to human MAG. The monoclonal antibodies developed differ with respect to immunoglobulin type, their specificity for human and/or rat MAG, and their recognition of protein or carbohydrate epitopes in MAG. In general, the antibodies that react with the protein backbone recognize both rat and human MAG, whereas a large number of the monoclonal antibodies recognize a carbohydrate determinant in human MAG that is not in rat MAG. Immunocytochemical staining of adult human spinal cord with the monoclonal antibodies resulted in periaxonal staining of myelin sheaths similar to that produced by well-defined, rabbit, polyclonal anti-MAG serum. In addition, the antibodies recognizing carbohydrate determinants in human MAG strongly stained oligodendrocyte cytoplasm. These monoclonal antibodies will be of value for the further chemical and biological characterization of MAG. PMID- 2582292 TI - [Metastatic intracranial germ cell tumor. Case report]. PMID- 2582294 TI - [Chondromyxoma in the middle cranial fossa. Case report]. PMID- 2582293 TI - [Intraventricular meningioma with intracerebral hemorrhage. Case report]. PMID- 2582295 TI - [Primary malignant lymphoma of the brain with marked size reduction by administration of prednisolone. Case report]. PMID- 2582296 TI - [Radiosensitive meningioma. Case report]. PMID- 2582297 TI - [Isodense epidermoid cyst in the pineal region. Case report]. PMID- 2582298 TI - [Ossification of multi-vertebral ligaments. Case report]. PMID- 2582299 TI - [Photoradiation therapy of experimental glioma]. PMID- 2582300 TI - [Recirculation in ischemic focus in the acute stage. Electron microscopical examination]. PMID- 2582301 TI - [Sequential changes in the autoregulation of cerebral blood flow in patients with vasospasm]. PMID- 2582302 TI - [Small saccular aneurysms in moyamoya disease]. PMID- 2582303 TI - Local anesthetic properties of opioids and phencyclidines: interaction with the voltage-dependent, batrachotoxin binding site in sodium channels. AB - [3H]Batrachotoxinin-A 20-alpha-benzoate ([3H]BTX-B) binds specifically and with high affinity (Kd = 30 nM) to a site on voltage-dependent Na+ channels. Compounds with local anesthetic activity inhibit the binding of [3H]BTX-B by a mutually exclusive, allosteric mechanism. The potential local anesthetic potency of a series of 23 opioids and phencyclidine-like compounds has been estimated by their inhibition of [3H]BTX-B binding to Na+ channels in a preparation of synaptoneurosomes from guinea pig cerebral cortex. The potency of these compounds were also tested as inhibitors of the specific binding of [3H]phencyclidine ([3H]PCP) to a high affinity site on rat brain membranes. Opioids such as morphine and codeine show little affinity for the [3H]BTX-B binding site or for the [3H]PCP binding site. Other analgesics, many of the PCP-like compounds and dioxadrol derivatives are potent versus [3H]BTX-B binding and display both stereospecificity and high affinity towards the PCP-binding site. However, there was no correlation between local anesthetic potency assessed as antagonism of [3H]BTX-B binding and affinity towards the PCP site. Five classical local anesthetics had no affinity for the PCP-site, but did displace [3H]BTX-B from its binding site. PMID- 2582305 TI - Excitatory neuropeptides activate opioid mechanisms in the guinea pig ileum. AB - A variety of peptides (corticotropin releasing factor (= CRF), cholecystokinin derived peptides, neurotensin, bombesin, angiotensin II, bradykinin and substance P) induce a contraction of the myenteric plexus/longitudinal muscle preparation of the guinea-pig ileum. This excitatory effect is rapid in onset and disappears within a few minutes in the continued presence of the peptide. A part of the contractile response is antagonized by atropine indicating that acetylcholine (ACh) is involved in this effect. Following cessation of the peptide-induced contraction, a second contractile response can be elicited by the opioid antagonist naloxone. The magnitude of this naloxone induced contraction is related to the "atropine-sensitive" component of the initial contractory effect of the peptides. It appears that the peptidergic excitatory action on the plexus which is associated with release of ACh, initiates the release of opioid peptides in this tissue. PMID- 2582304 TI - Chloroacryloyl amides and alpha-methylenelactones from naltrexone, oxymorphone and fentanyl. AB - A series of chloroacryloyl amides and alpha-methylenelactones were prepared from naltrexone and oxymorphone and some chloroacryloyl amides from fentanyl were prepared as potential Michael acceptors and irreversible ligands. The relative rates of Michael additions of p-methoxybenzenethiol to the double bonds were measured in an NMR spectrometer. The IC50's in rat brain homogenates and the irreversible binding to rat brain membranes were determined. In the methylene lactone series, it was found that both the alpha and beta isomers derived from naltrexone and oxymorphone were excellent Michael acceptors, but only the beta isomers were more active in the opioid binding assays. The beta isomer derived from naltrexone was an irreversible ligand whereas the oxymorphone analogue was active only in the presence of 100 mM NaCl. In the chloroacryloyl series, only the alpha-chloroacryloyl amide derived from beta naltrexamine proved to be an irreversible binding ligand in the absence of NaCl. It was an excellent Michael acceptor. Under the conditions of our experiments, beta-FNA was a poor Michael acceptor and did not behave as an irreversible ligand in rat membranes. PMID- 2582306 TI - Experiments on the use of hormones of the posterior pituitary in memory disorders of various genesis. PMID- 2582307 TI - The comparative distribution of enkephalin, dynorphin and substance P in the human globus pallidus and basal forebrain. AB - Three neuropeptides, enkephalin, dynorphin, and substance P appear in the globus pallidus in a unique pattern termed woolly fibers as described previously [Haber and Nauta (1983) Neuroscience 9, 245-260]. The comparative distribution of these fibers are described in the human globus pallidus and basal forebrain area. The results show two main points: The human globus pallidus is a larger, more intricately shaped structure than previously thought, invading several limbic related basal forebrain regions. There are differences in the distribution patterns of the neuropeptides described, so that they are found in overlapping, but not matching regions. The relationship between the peptide distribution and what is known about the functional (limbic vs motor) circuitry of the region is discussed. PMID- 2582309 TI - Substance P, enkephalins, somatostatin, cholecystokinin, oxytocin, and vasopressin in human spinal cord. AB - Several neuropeptides were immunohistologically studied in normal human spinal cords. Substance P, methionine-enkephalin, leucine-enkephalin, and cholecystokinin positive fibers were found in all cytoarchitectonic layers, with a specific distribution pattern for each peptide. Somatostatin, oxytocin, and vasopressin immunoreactivities were restricted to particular spinal layers. Perikarya and proximal dendrites were visualized and classified by comparison with previous Golgi analyses. Substance P was contained in "radiate cells" of layer III, methionine-enkephalin in marginal neurons as well as in layer II "stellate cells," and somatostatin in layer II "islet cells." Several results differed from those reported in other species. Chemical neuroanatomy may provide new insights into the neuronal organization of the human spinal cord. PMID- 2582308 TI - Rapid axonal transport of three molecular forms of acetylcholinesterase in the frog sciatic nerve. AB - Acetylcholinesterase occurs in the frog sciatic nerve under five stable molecular forms with distinct sedimentation coefficients in sucrose gradients: 3 globular forms (3.6S, 6S and 10.5S) and two asymmetric ones (14S and 18S). Whereas in birds and mammals, the asymmetric tailed forms of acetylcholinesterase are present in trace amounts in peripheral nerves and account for only a small part of the enzyme activity submitted to a rapid axonal transport, the two asymmetric 14S and 18S forms represent nearly 50% of total activity in the frog sciatic nerve and account for 60-70% of the acetylcholinesterase activity accumulated at both sides of a nerve transection, the rest being due to an accumulation of globular molecules. We showed that the three forms, 10.5S, 14S and 18S, are all carried with the fast phase of axonal transport at a velocity of 100-120 mm/day in the anterograde direction and 20-30 mm/day in the retrograde direction. The velocity of transport for the light molecular forms 3.6S and 6S could not be calculated. In addition, we observed that large amounts not only of the 10.5S but also of the asymmetric 14S and 18S forms appear to be stationary along the frog sciatic nerve, contrary to the situation described for peripheral nerves in birds or mammals. Our results thus reveal that some axonal transport parameters for the asymmetric forms of acetylcholinesterase greatly differ in the peripheral nerves of amphibians on the one hand and of birds and mammals on the other, suggesting that these heavy molecular forms might have distinct functions in the nerves of lower and higher vertebrates. PMID- 2582311 TI - [Carcinoma of the middle rectum. Immediate and long-term results; comparison of Miles' operation and ALR with manual anastomosis and ALR with mechanical anastomosis]. PMID- 2582310 TI - Lesch-Nyhan syndrome: CSF neurotransmitter abnormalities. AB - Serial determinations of spinal fluid homovanillic acid (HVA) and 5 hydroxyindoleacetic acid (5-HIAA) were made in four patients with the Lesch-Nyhan syndrome over a 5-year period. Control spinal fluids for age-matched comparison were obtained from 194 neurologic and nonneurologic pediatric patients. A rapid decline in control spinal fluid HVA and 5-HIAA occurs over the first 3 years of life (50 and 60%, respectively), and a more gradual decline persists throughout adolescence. The Lesch-Nyhan subjects have similar age-related changes in their spinal fluid neurotransmitter levels. Sequential 5-HIAA determinations from the four Lesch-Nyhan boys fall within the control range. The Lesch-Nyhan HVA levels are lower than the mean value for the age-matched control group in 18 of 19 samples. Ten of 19 determinations fell below the control range. Our findings provide evidence for altered CNS dopamine metabolism in the Lesch-Nyhan syndrome. PMID- 2582312 TI - [Variability of the clinical and laboratory aspects in the presentation of chronic liver diseases in relation to their etiology. Analysis of a case study and review of the literature]. AB - 247 cases of patients suffering from chronic liver diseases were reviewed. These cases were divided according to "risk areas" (viral, alcoholic, viral and alcoholic, cryptogenic) and diagnosis (CAH, compensated cirrhosis, decompensated cirrhosis). Differences found in clinical and laboratory aspects of liver diseases from different risk areas are described but it is concluded that no single aetiology affects the liver functional reserve more than the others. Laboratory tests give more information in the early stages of chronic liver diseases while clinical analysis is more varied in the terminal ones. Literature on the subject is reviewed. Our data neither confirm nor disprove that HBsAg+ Alcohol+ patients display a characteristic clinical picture and this hypothesis should be further investigated. PMID- 2582313 TI - [Comparison between the gastrointestinal tumor antigen and the carcinoembryonic antigen in diseases of the digestive tract]. AB - Recently a glycolipid antigen known as gastrointestinal cancer antigen (GICA) has been proposed as a new seral marker of gastrointestinal and pancreatic tumours. This antigen is specifically recognised by a monoclonal antibody and biologically and immunologically distinguished by carcinoembryonic antigen (CEA). Out of 438 subjects including: 60 blood donors, 205 patients suffering from digestive tract tumours, subdivided into different organs 21 gastric ca's, 60 colon ca's, 100 pancreatic ca's and 24 liver cancers) 173 subjects with inflammatory gastrointestinal complaints, also divided by organ 18 gastric ulcers, 45 inflamed colons, 60 chronic pancreatitis and 50 liver cirrhosis). GICA and CEA radioimmunoassays were carried out (Sorin GICAK and CEAK) to evaluate sensitivity, specificity and predictive accuracy. Normal threshold levels were set at 30 ng/ml for CEA and 40 mu/ml for GICA. These levels represent the mean + 2DS of levels measured in 260 patients hospitalised for various benign and functional complaints and differ from cancer patient results by the largest amount. All blood donors, whether smokers or not, give lower values than these. Results show GICA gives a lower overall number of false positives than CEA (20% as against 9.6%). GICA diagnostic results were more accurate overall for the entire case sample examined. GICA gave higher percentage positives than CEA for individual tumour types: pancreatic ca (82% v 52%), liver cancer (70.8% v 20.8%) and gastric ca (47.6% v 33%). CEA appears to work better than GICA in the case of colorectal ca's (56% v 41%). Both markers were found to be more sensitive in the presence of tumours with metastases. GICA is the best currently available marker of pancreatic tumours thanks to its sensitivity, specificity and predictive accuracy. Although GICA gave good results in cases of liver cancer, these did not exceed those obtained with alpha foetoprotein. In the other cases of digestive tumours examined, a combination of GICA and CEA investigation techniques appears to be the best non-invasive method currently available for patient follow-up. PMID- 2582314 TI - [MacDuffie's syndrome (or allergic hypocomplementemic vasculitis). Observations on 2 cases]. PMID- 2582315 TI - [Multiple neoplastic combinations in the aged. Case contribution]. AB - Four cases of patients suffering from more than one type of neoplasia are described. Plasmocytoma was found in three of the four cases. Links between old age, cancer and immunity are put forward in relation to the geriatric age of the four patients. PMID- 2582317 TI - Diphenylhydantoin reduces veratridine-induced sodium permeability in frog skeletal muscle. AB - The effect of the anti-epileptic drug 5,5'-diphenylhydantoin (Dilantin) on Na permeability (PNa) in frog skeletal muscle was studied. Because there is no detectable tetrodotoxin-sensitive Na permeability in resting frog muscle, PNa was induced using the alkaloid 'neurotoxin' veratridine. Veratridine has been previously characterized as a useful 'tool' for producing a population of open Na channels in frog muscle. The amount of sodium permeability produced by veratridine was quantified in two ways: by measuring (a) membrane potential (Vm) and (b) 22Na influx. Dilantin was shown to reverse veratridine-induced depolarization by approximately one-third and to inhibit veratridine-induced Na influx in a dose-dependent manner, with an apparent Km of 78 +/- 8 microM. PMID- 2582316 TI - Effects of intravenously administered 6-hydroxydopamine on the content of monoamines in the median eminence and neurointermediate lobe of the rat. AB - The effects of intravenous administration of 6-hydroxydopamine (6-OHDA) on the content of catecholamines in the median eminence and neurointermediate lobe was studied in male rats. The results confirmed previous findings of a depletion of catecholamines in both regions as a result of this lesion, although the magnitude of the effect was less than that revealed by fluorescence histochemistry. Administration of desipramine before 6-OHDA injection produced a more specific lesion, depleting dopamine but leaving noradrenaline unaffected. PMID- 2582318 TI - Beta-carboline analogues of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP): endogenous factors underlying idiopathic parkinsonism? AB - A remarkable structural similarity exists between the parkinsonian neurotoxin, N methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), and 2-[N]-methyl-tetrahydro beta-carboline (2M-THBC), a tryptamine-derived alkaloid which can be biosynthesized in brain. To explore whether the beta-carboline also has neurotoxic effects, owl monkeys were treated daily with MPTP or 2M-THBC. Acute behavioral similarities were seen, but 2M-THBC did not induce persistent parkinsonism, nor did it cause apparent loss of nigral cells. However, 2M-THBC resembled MPTP in reducing 3,4-dihydroxyphenylacetic acid levels in caudate and in altering levels of serotonin and 5-hydroxyindoleacetic acid in substantia nigra. These limited similarities should be considered in the light of relationships between neurotoxicity, MPTP versus 2M-THBC oxidation, and the chronicity of human Parkinson's disease. We suggest that N-methylated beta carboline species, possibly accumulating during stress and aging, could well be causative factors in parkinsonism. PMID- 2582319 TI - Ionic currents in neuroblastoma clone E-7 cells. AB - Ionic currents were studied in exponentially growing neuroblastoma cells (clone E 7) derived from mouse neuroblastoma C-1300 with the patch-clamp technique in the whole cell mode (Pflugers Arch., 391 (1981) 85-100). In differentiated cells, with one or several processes, an early inactivating inward current approximately equal to 50 microA/cm2 was observed in response to depolarizing steps from the holding potential -60 to -70 mV, which was insensitive to 2 microM tetrodotoxin but readily blocked by Co2+ (6 mM). This inward current was followed by a delayed outward current which was eliminated by 12 mM tetraethylammonium. In the undifferentiated cells, only delayed outward current was observed. It is suggested that, in differentiated cells both Ca2+ and delayed rectifier K+ channels exist, while only the latter are present in undifferentiated cells. PMID- 2582321 TI - Photographs as organizational aids for the skill laboratory. PMID- 2582320 TI - Use of the fluorescent retrograde tracer, Granular blue, in crustacean motor system studies. AB - Retrograde axonal transport and fluorescent retrograde labelling of neurons were investigated in a crustacean motor system. A fluorescent tracer (Granular blue) was injected into an antennal muscle of rock lobster in order to identify the motor neurons innervating it. After an appropriate post-injection survival time, the fluorescent tracer was found to have labelled motor neurons in the central ganglion. This result indicates that after uptake by the axon terminals, the fluorescent tracer was retrogradely transported through axons of motor neurons to the parent cell bodies. PMID- 2582322 TI - Genetic amniocentesis: significance of intraamniotic bleeding and placental location. AB - Simultaneous ultrasound was used to determine if there was a correlation between visualized intraamniotic bleeding, placental location, and fetal-maternal hemorrhage. It was hoped to then determine which Rh-negative patients should receive Rh immunoglobulin. Visualized intraamniotic bleeding showed no correlation to fetal-maternal hemorrhage. Intraamniotic bleeding was commonly associated with needle insertion through an anterior placenta, but also occurred regardless of placental location and in the absence of placental needle traversal. No correlation was found between placental location and fetal-maternal hemorrhage as evidenced by evaluation of maternal serum alpha-fetoprotein. The Kleihauer test was not as sensitive as alpha-fetoprotein. PMID- 2582323 TI - [Age-related characteristics of the cytochemical reaction of the cornea to ultrasonics]. PMID- 2582324 TI - [Immunohistochemical demonstration of tumor-associated antigens in urinary bladder carcinomas using mono- and polyclonal antisera]. AB - Keratin was found in more than 90% of transitional cell carcinomas of the bladder in the cytoplasma with polyclonal antibodies. Intensity increased with dedifferentiation. Cytokeratin was detected with monoclonal antibodies in more than 80%. Squamous cell carcinoma of the urinary bladder was always strongly positive for keratin and cytokeratin. CEA was found in 20% of G1 and 40% of G2 and G3 carcinomas of the urinary bladder. The prostatic epithelium markers PSA and PAP were always negative also Ca1. PMID- 2582325 TI - [AML-6 study of the value of cyclic alternating chemotherapy during remission in acute myelocytic leukemia]. AB - Twenty-five institutions are participating in a randomized trial of the E.O.R.T.C. for improvement of remission incidence, disease-free interval and survival in adult acute non-lymphocytic leukemia. In order to delay the time of relapse, an intensive cyclic therapy is employed early after achievement of complete remission (C.R.) using either the same drugs of the induction regimen or rotating combinations of alternative drugs, e.g. mAMSA, 5-AZA and HD-Ara C. So far 266 patients entered the trial with a median age of 45 yrs. The overall C.R. rate is 71%; 52% of the responders reached C.R. after 1 cycle of induction treatment. 10% of the patients died within the first 7 days of induction or due to hypoplasia, 13% were absolute resistant to this regimen. Fifty-eight patients are randomized to 'maintenance' arm I, 54 to arm II, 79/112 patients are still under study. Treatment toxicity is tolerable. In 7% and 3% excessive toxicity was a reason for going off study during induction or 'maintenance'. As far as remission duration or survival within the two treatment arms is concerned, it is too early to draw any conclusions. PMID- 2582326 TI - Immune complexes and acute phase proteins in human cancer: preliminary evaluation by laser nephelometric techniques. AB - The serum levels of circulating immune complexes (IC) were evaluated by a new 'direct' laser nephelometric assay, concomitantly with four acute phase proteins (APP), in 167 patients with various neoplasms at different stages. The present study confirms the presence of IC in the sera of cancer patients and, in the breast cancer group, there is a significant correlation with the progression of the disease. Among the APP, in several cancer groups, C-reactive protein, haptoglobin and alpha 1-acid glycoprotein are more elevated than in controls, and a trend to display higher values is observed in the subjects with metastatic disease; particularly, the frequency of patients with 3 or more proteins above the normal levels is significantly higher in metastatic than in localized cancers (p less than 0.09). PMID- 2582327 TI - Serum interferon as a biological marker in malignant tumors. AB - A total of 745 serum interferon (IFN) determinations were carried out on the serum of 332 cancer patients with a variety of tumors. Disease activity was defined as either 'active' or 'nonactive' as based on clinical examination, the results of laboratory tests and radiological criteria. IFN levels were estimated for both disease activity and mode of treatment. A statistically significant higher level of IFN in the serum of active, as compared to that of nonactive disease, was established. Furthermore, a slight increase in the IFN level was observed in patients before initiating chemotherapy as compared to untreated patients, followed by a decrease in those patients undergoing chemotherapy. These differences between groups were not found to be statistically significant. However, in the cases of rectum, prostate and female genital cancers, a significant elevated level of serum IFN was observed at a late stage of the disease, followed by a decrease after chemotherapy treatment. In addition, a significant lower level of serum IFN was detected in breast cancer patients shortly after radiotherapy as compared to those before radiotherapy. We conclude that IFN, known to play a role in the control mechanisms of developing malignant processes, can be determined in the serum and used to monitor disease activity in individual patients. The inhibition of IFN release depends in part on therapy and can be used for monitoring treatment schedules along the course of disease. PMID- 2582328 TI - Selective staining reactions of involved blood cells prior to symptoms of lymphatic leukemia in mice. AB - After inoculation with lymphatic leukemia virus, blood smears were obtained daily from young Balb/c mice. When the smears were stained with silver nitrate, a cytoplasmic granular deposition was first observed in the circulating polymorphs with a subsequent abrupt disappearance of any staining reaction in the cytoplasm. No further cytoplasmic reaction was noted in these cells. The mononuclear cells demonstrated a gradually increasing intracytoplasmic concentration of granules. Prior to the appearance of leukemic symptoms, the lymphoid cells showed extensive vacuolization. It is suggested that this staining procedure affords a means for identifying cells undergoing malignant transformation before symptoms are discernible in the host. PMID- 2582329 TI - Long-term diabetic vitrectomy results. Report of 10 year follow-up. AB - Ten year follow-up examinations were obtained on 72 cases having pars plana vitrectomies for diabetic retinopathy complications from 1970 to 1973. Forty-two percent of the cases maintained 6/60 or better visual acuities through the tenth year. The visual results were quite stable, with 53% of the cases having the same or better visual acuities at ten years compared with six months. Neovascular glaucoma developed in 11 eyes, usually during the first six months, and open angle glaucoma developed in 16 eyes, usually after the five-year follow-up examination. Both types of glaucoma occurred almost exclusively in aphakic eyes. Cataracts developed in 75% of retained clear lenses. The vitreous cavities remained clear in 67% of the eyes, and the maculas were attached in 65% of the eyes 10 years following vitrectomy. Fundus neovascularization did not recur. PMID- 2582330 TI - Diabetic dense premacular hemorrhage. A possible indication for prompt vitrectomy. AB - A review was undertaken of nine eyes of nine patients who suffered tightly bound dense premacular hemorrhage as a complication of proliferative diabetic retinopathy. Patients who did not receive vitrectomy within four weeks of the onset of the hemorrhage all progressed to late macular traction and visual acuity no better than 6/30. Of the five patients who received vitrectomy within four weeks of the onset of the hemorrhage, none developed significant late macular traction and all achieved visual acuity of 6/12 or better. It is possible that the tightly bound dense premacular hemorrhage represents an indication for vitrectomy within one month of its onset. PMID- 2582331 TI - Diabetic choroidopathy. Light and electron microscopic observations of seven cases. AB - The choroid of seven young patients (ages 20-29 years), who had had diabetes mellitus for many years (14-23 years) was studied by light and electron microscopy. The eight enucleated eyes were blind and painful as a complication of diabetes mellitus. Histopathologically, the choriocapillaris and other small choroidal blood vessels disclosed marked basement membrane thickening of their walls. Periodic acid-Schiff-positive homogeneous acellular nodules were present and resembled those of diabetic glomerulosclerosis (Kimmelsteil-Wilson disease). Some choroidal arteries were arteriosclerotic. Choroidal compromise was suggested by luminal narrowing of the capillaries, capillary dropout, and focal scarring. Choroidal neovascularization with subretinal fibrovascular membranes occurred in two patients at the midperiphery and periphery, and resembled those of retinitis proliferans. Leakage of proteinaceous fluid into the choroidal stroma and beneath the focally detached pigment epithelium was suggested by the electron microscopic observations. Choroidal vasculopathy in diabetes mellitus is similar to much of what has been described in other tissues of the eye and body, and suggests an important role in the pathogenesis of diabetic retinopathy since the outer retinal layers are largely dependent on the choroid for their nutrition and oxygenation. PMID- 2582332 TI - Chorioretinal and choriovitreal neovascularization after photocoagulation for proliferative diabetic retinopathy. A clinicopathologic correlation. AB - A patient with proliferative diabetic retinopathy was treated by panretinal and focal photocoagulation. Later, he developed one area of clinically diagnosed chorioretinal and choriovitreal neovascularization (CNV), neovascular glaucoma, and a blind painful eye necessitating enucleation. Clinicopathologic correlations of this eye including fundus photography, fluorescein angiography, light and electron microscopy are reported. Histopathologic examination revealed three areas of CNV, suggesting that some CNV may go undetected clinically also in other cases and thus may occur more frequently than evident from the literature. Our CNV occurred at sites of focal treatment. Retreatment of one area was unsuccessful. Choriovitreal neovascularization passed through discontinuities of Bruch's membrane into the retina and showed fenestrae of the endothelial cells. Endothelial fenestrae may account for the profuse fluorescein leakage seen clinically in CNV. PMID- 2582333 TI - Update on antiviral agents. AB - Recent evidence indicates that many of the characteristics of herpes simplex virus (HSV) ocular disease are determined by the genome of the virus strain. The type and severity of epithelial disease, as well as the morphology of the lesions, have been demonstrated to be genetically controlled, and the region of the viral DNA responsible for these aspects of the disease has been identified. In addition, the frequency of reactivation of the latent virus may be inherent in the genetic makeup of the virus, although host factors appear to influence the appearance of frank disease. Drugs for the treatment of epithelial herpes inhibit virus replication in the host cells; the newest and most effective drug, trifluridine, heals 97% of epithelial lesions within two weeks. The place of thymidine kinase selective drugs in ophthalmology has not been determined. There are, as yet, no drugs specific for stromal herpes, and no drugs have been shown to eradicate the latent virus from the ganglia or to prevent the recurrence of ocular herpetic disease. PMID- 2582334 TI - Ocular findings in incontinentia pigmenti. AB - Incontinentia pigmenti is an uncommon disorder affecting females, and is associated with ocular, dental, skeletal, and central nervous system abnormalities. Ocular abnormalities are found in 35% of cases. The authors present an eight-month-old girl with neonatal history of skin bullae, who was noted to have esotropia, leukocoria, and a fixed pupil. Histologic examination of the enucleated globe reveals total retinal detachment with retinal neovascularization into the collapsed vitreous, reactive retinal gliosis, and scattered giant nodular proliferations of retinal pigment epithelium. It is suggested that the underlying defect is at the level of the retinal pigment epithelium and that the neurosensory retinal changes are secondary. PMID- 2582335 TI - Anterior chamber tube shunt to an encircling band in the treatment of neovascular glaucoma and other refractory glaucomas. A long-term study. AB - Long-term follow-up results of the anterior chamber tube shunt to an encircling band (ACTSEB) procedure are reported. Thirty eyes of 28 patients with neovascular glaucoma (Group I) and five eyes with non-neovascular refractory glaucoma (Group II) underwent this procedure. In Group I, the average preoperative intraocular pressure (IOP) was 57.1 mmHg. After surgery and average followup of 25 months 96% of eyes had a successful outcome with an average IOP of 15.8 mmHg (P less than 0.001). In Group II, despite multiple glaucoma surgical procedures, the average preoperative IOP was 54 mmHg. After surgery and average followup of 20 months 80% of eyes had a successful outcome with an average IOP of 19.8 mmHg (P less than 0.01). Revisions in our surgical technique utilizing a small entry with a 25 gauge needle into the anterior chamber and use of Healon resulted in a fully formed anterior chamber by two days. Clinical and experimental evidence is presented which suggest that aqueous filters through the tube to a reservoir around the encircling band. PMID- 2582336 TI - Ghost cells in complex odontoma: a light microscopic and SEM study. AB - Ghost cells in complex odontoma were studied by light microscopic and scanning electron microscopic examination of decalcified sections. They were found at different locations in odontomas: next to tubular dentin, at the site where enamel would be expected; adjacent to remnants of enamel matrix or surrounded by enamel matrix; within granular calcified masses in contact with bone or tubular dentin; in contact with ameloblasts or adjacent to small rests of odontogenic epithelium. They were either isolated or arranged in groups. Their cytoplasm presented a fibrillar component and a lack of keratohyaline. In a complex odontoma, ghost cell keratinization occurs as a result of metaplastic transformation. The calcifying process in these cells was found to be a passive one, with the cells becoming gradually entrapped within the calcified material- bone, osteoid, dentin, dystrophic osteodentin, or dystrophic granular or lamellar types of calcification. Complex odontomas contain both normal and metaplastic odontogenic epithelial cells, which may have lost their developmental and inductive properties. PMID- 2582337 TI - Inhibition of bleomycin lung toxicity by N-acetyl cysteine in the rat. AB - N-acetyl cysteine (NAC) has recently been shown to have antioxidant properties, and since bleomycin produces pulmonary damage via free oxygen radical toxicity, the possible protective effect of NAC on bleomycin lung toxicity was investigated. Rats received saline (n = 7), NAC (n = 6), bleomycin (n = 7) or bleomycin and NAC (n = 6) by direct intratracheal injection. Seven days later the animals were killed and the lungs processed for histology or morphometry. All rats treated with bleomycin only had typical changes of bleomycin lung toxicity whereas the animals treated with bleomycin and NAC had minimal pathology. The control animals had normal lungs. These results were confirmed by morphometry which demonstrated significantly higher volume densities (p less than .01) of alveolar wall and free alveolar cells in the bleomycin group compared to the other 3 groups. It is concluded that NAC inhibits bleomycin lung toxicity when administered by direct intratracheal injection. PMID- 2582338 TI - Speaking personally: monoclonal antibodies as diagnostic reagents. AB - It is 10 years since Kohler & Milstein published the first paper describing the laboratory production of a monoclonal antibody. In those 10 yr monoclonal antibodies have caused a revolution in Immunology and in some branches of Pathology. After a surprisingly slow initial reaction, the scientific community has embraced the new technique enthusiastically, indeed overenthusiastically. Inevitably, excessive enthusiasm was followed by disappointment. There can be no doubt that monoclonal antibodies provide opportunities for major improvements in diagnostic specificity and resolving power. It is equally clear that monoclonal antibodies do not solve all analytical problems, and have a few problems of their very own. This brief review presents one man's assessment of the place of monoclonal antibodies as diagnostic reagents and discusses the properties of the antibodies and the parameters of the assay which most influence the successful use of diagnostic tests based on monoclonal antibodies. PMID- 2582340 TI - Augmentative communication: a perspective for pediatricians. AB - This article has described the rationale and methods available for treatment of severely communicatively impaired children. The primary goal of such intervention is to facilitate communication, rather than speech per se, as the most realistic goal for some youngsters. To the extent that augmentative techniques affect speech development, however, they have been shown to exert a facilitory, rather than inhibitory, effect. The relatively new phenomenon of aided augmentative communication for non-speaking youngsters is still in its infancy. Service professionals in the medical, clinical, and research fields must continue to discern ways to practically apply these instruments to the task of human communication interchange. PMID- 2582339 TI - [Characteristics of the resuscitation of dogs immunized with a foreign protein and sheep erythrocytes]. PMID- 2582343 TI - Comparison of the carbohydrate composition of alpha 2-macroglobulin from patients with cystic fibrosis and normal controls. AB - The putative involvement of alpha 2-macroglobulin (alpha 2M) in the pathogenesis of cystic fibrosis has long been a subject of controversy. Previous reports have indicated that there are alterations in the carbohydrate moieties of alpha 2M in the disease. In the present study the carbohydrate composition of alpha 2M isolated from the plasma of six patients with CF was compared to that of alpha 2M from six age- and sex-matched normal controls. The carbohydrate composition of CF alpha 2M expressed as mean mumol carbohydrate +/- SD per 100 mg protein was: fucose 0.70 +/- 0.12; mannose 14.07 +/- 1.31; galactose 6.72 +/- 0.65; glucosamine 15.38 +/- 1.59; sialic acid 5.52 +/- 0.33 while that of normal control alpha 2M was: fucose 0.69 +/- 0.11; mannose 14.42 +/- 1.21; galactose 6.91 +/- 0.52; glucosamine 16.13 +/- 1.77; sialic acid 5.58 +/- 0.31. Therefore, contrary to previous reports, this paper demonstrates that there is no difference in the carbohydrate composition of alpha 2M in cystic fibrosis. PMID- 2582341 TI - Practical approaches to assessing liver function. PMID- 2582342 TI - Cancer chemotherapy in infants and children. AB - The narrow therapeutic index and potentially life-threatening toxicities of the antineoplastic agents require a clear understanding of their toxicologic and pharmacologic properties, particularly in infants and children. This article reviews the literature published in the last five years on pediatric cancer chemotherapy. It begins with an overview of new concepts in antineoplastic therapy and then summarizes each of the main drugs used to treat the cancer of infants and children. PMID- 2582344 TI - Increase of F cells during acute hemolysis in glucose-6-phosphate dehydrogenase deficient males. AB - Five male Sicilian children with glucose-6-phosphate dehydrogenase deficiency were studied shortly after hemolytic crisis in order to evaluate the immediate effects of massive hemolysis on fetal Hb (HbF) levels and the number of circulating F cells. Hematological values seen 4 months after the children recovered from the crisis were considered representative of the patients' steady state. All patients had an increase in HbF levels (2.26 +/- 0.24%) and F cell number (29 +/- 4.79%) in the acute phase and their HbF values and F cells returned to normal range at control. Globin synthesis was balanced in the peripheral blood and bone marrow and there was a small peak of gamma chains. Globin chain electrophoresis showed that both G gamma and A gamma genes were active in all patients. These results confirm that hemolytic stress produces increased F cell release in peripheral blood. Such release is rapid enough (less than 72 h) to be consistent with the hypothesis of an induction of HbF synthesis in late erythroid precursors. PMID- 2582346 TI - [Assessment of the mental development of young children]. PMID- 2582345 TI - [Activity of proteolytic enzymes, their inhibitors and amylase of the blood in toxicoses in young infants]. PMID- 2582347 TI - [Comparative evaluation of the effectiveness of different methods of prophylactic treatment for children with bronchial asthma]. PMID- 2582348 TI - The relationship between total protein in serum, glutaraldehyde coagulation test and disease in feedlot calves. AB - Serum from in all 249 calves were used to correlate the level of total protein (serum-Tp), gamma-globulin and the reaction of glutaraldehyde coagulation test (GCT) to each other. Further, of the 249 calves 219 were bled within two days after arrival to a feedlot and serum-Tp and GCT were related to subsequent diseases. The results revealed a close relationship between the three tests. Of the 219 calves 15% had a negative GCT (hypogammaglobulinemia) and 26% had a serum Tp below 55 g/l. There was a significantly (p less than 0.001) higher disease frequency, 81%, in the GCT negative calves than in the GCT positive, 35%. Serum Tp was significantly (p less than 0.001) higher in healthy compared to diseased calves. The mean values were 60.6, 57.2, 55.2 and 53.1 g/l for healthy calves, calves with respiratory disease, enteritis and both respiratory disease and enteritis respectively. Further, calves with a serum-Tp below 55 g/l developed disease earlier after arrival to the feedlot than those above this limit. It was concluded that both serum-Tp and GCT can be used in field investigation to identify calves predisposed to disease. PMID- 2582350 TI - DNaseI sensitivity of the rat albumin and alpha-fetoprotein genes. AB - We have analyzed the DNaseI sensitivity of chromatin from the rat albumin and alpha-fetoprotein genes in the fetal liver (which synthesizes albumin and alpha fetoprotein), adult liver (which synthesizes albumin), fetal yolk sac (which synthesizes alpha-fetoprotein), and adult kidney (which synthesizes neither). Active genes were much more sensitive than their kidney counterparts, and the adult liver alpha-fetoprotein and fetal yolk sac albumin genes showed intermediate levels of sensitivity. Sensitivity was analyzed as a function of the extent of DNaseI digestion. Rate constants were calculated for the degradation of individual DNA hybridization bands and normalized to the intrinsic rate constants of the same bands degraded in purified DNA. This enabled us to eliminate the inconsistencies that otherwise result from comparing chromatin sensitivity of different DNA sequences, or chromatin sensitivity in different nuclear environments. PMID- 2582349 TI - Molecular cloning of mouse PSP mRNA. AB - PSP is the most abundant translation product of mouse parotid glands where its production is co-ordinated with that of salivary amylase. The synthesis of these two proteins apparently is restricted to this tissue. In order to enable us to study common regulatory elements in the genes of the two proteins, double stranded cDNA, synthesized for parotid gland poly (A)+ RNA, was cloned. DNA sequencing of three clones complementary to the most abundant messenger indicated overlap and resulted in a total sequence of 867 nucleotides. Translation of this sequence revealed that at one end the amino acid sequence was the same as the N terminal sequence of PSP. The sequence contains 60 nucleotides coding for part of or the complete signal peptide, 645 nucleotides coding for the PSP protein, and 162 nucleotides that apparently are not translated. Southern blot analysis suggests a simple structure for the PSP gene in mouse and man. PMID- 2582351 TI - Common structural features of the genes for two stable RNAs from Halobacterium halobium. AB - The genes coding for the 5S rRNA and another stable RNA, termed 7S RNA, in Halobacterium halobium were isolated from a genomic library of this archaebacterium and their nucleotide sequences determined. Both genes are colinear with their transcripts (5S rRNA and 7S RNA), but 5S rRNA and possibly also 7S RNA isolated from other halobacteria carry additional nucleotides within the RNA transcript. Both genes are located in the G + C rich chromosomal fraction I of H. halobium. Comparison of the 3' non-coding regions of both genes shows a 20 bp sequence of high homology immediately at the 3' ends which is almost symmetrically flanked by two stem-loop structures, one being situated close to the 3' end but within the coding region and the other downstream of the common 20 bp sequence. PMID- 2582353 TI - Mammalian single-stranded DNA binding proteins and heterogeneous nuclear RNA proteins have common antigenic determinants. AB - Antibodies were raised in rabbit against a pure subset of calf thymus single stranded DNA binding proteins (ssDBPs) and purified by affinity chromatography on antigen-Sepharose. In Western blot experiments these antibodies were shown to react to the same extent with the whole family of bovine ssDBPs, as well as with ssDBPs from HeLa cells. When used to stain total cell extracts from both calf thymus and HeLa cells the antibodies reacted only with bands corresponding to the ssDBPs and with a set of bands of higher molecular weight, whose electrophoretic pattern matched that of the 40S hnRNP core proteins. In effect we observed that purified 40S hnRNP core proteins from HeLa cells were strongly reactive with the antibodies. Moreover after partial tryptic digestion HeLa cells ssDBPs and hnRNPs produced immunoreactive fragments of the same molecular weight and isoelectric point. Extensive structural homologies can thus be evidenced between these two classes of proteins, which share the property of selective binding to single stranded nucleic acids. PMID- 2582352 TI - Chemical and enzymatic biotin-labeling of oligodeoxyribonucleotides. AB - Biotin has been converted to 2-(biotinylamido)ethanol and condensed to phosphorylated oligonucleotides in a solid phase synthesis. The 5'-biotinylated oligonucleotides were enzymatically coupled to other DNA fragments by T4 DNA ligase or T4 RNA ligase. The hybridization properties of such biotin-labeled oligonucleotide probes were studied. PMID- 2582354 TI - The gene for an exported antigen of the malaria parasite Plasmodium falciparum cloned and expressed in Escherichia coli. AB - An exported protein of the erythrocytic stages of the malaria parasite, Plasmodium falciparum, has epitope(s) in common with the surface of the sporozoite stage (1). Two cDNA clones encoding this protein, Ag5.1, have now been isolated and expressed in Escherichia coli. The coding sequence contains a region with strong homology to that of the circumsporozoite protein of P. falciparum. Other features of the sequence can be explained in terms of the observed behaviour of the protein in the parasite life cycle. The Ag5.1 can now be synthesised in bacteria in sufficient amounts to analyse the immune response to this protein. PMID- 2582355 TI - Hyperacetylated histones facilitate chromatin assembly in vitro. AB - We have examined the effect of histone acetylation on the in vitro assembly of nucleosomes with DNA and purified histones at physiological ionic strength in the presence of polyglutamic acid. We have found that hyperacetylated histones assemble nucleosomes with greater efficiency, and to a greater extent, than either control or hypoacetylated histones. Assembly reactions were performed over a range of histone to DNA ratios (0.25 to 3.0, w/w) and polyglutamic acid to histone ratios (0 to 1.6, w/w). Although polyglutamic acid may act as a sink to prevent nonspecific histone-DNA interactions, our data suggest that the polyanion primarily facilitates the assembly of nucleosomes by organizing histones into a form that is amenable to deposition. PMID- 2582356 TI - Structure of the sea urchin U1 RNA repeat. AB - The genes coding for U1 RNA in the sea urchin L. variegatus are present in a 1400 base pair tandem repeat. One member of the repeat has been cloned and its sequence determined. The repeat unit contains a single copy of the gene for L. variegatus U1 RNA. This gene encodes an RNA which is 75% homologous to mammalian U1 RNA. The L. variegatus U1 RNA could assume a secondary structure similar to that proposed for other U1 RNAs. In addition the L. variegatus U1 RNA is precipitated by anti-SM and anti-RNP antisera. Analysis of the L. variegatus genomic DNA using the cloned U1 gene as a probe reveals a major and a minor type of repeat unit. The two repeated units are the same length but differ in a number of restriction enzyme sites clustered 200-500 bases down-stream from the gene. The monomer we have cloned and sequenced is a representative of the minor repeat. A sequence (GATAA) which is -41 to -37 bases 5' to the gene has homology to the putative RNA polymerase II promoter. Fifteen bases 3' of the gene is a sequence (CAAAGAAAGAAAA) which is very similar to the sequence found 3' of the sea urchin histone genes. The two Hha I, Hpa II and Ava I sites in the repeat are all unmethylated in sperm DNA. PMID- 2582357 TI - Characterization of cloned human alphoid satellite with an unusual monomeric construction: evidence for enrichment in HeLa small polydisperse circular DNA. AB - A recombinant DNA plasmid library was constructed from HeLa cell extrachromosomal circular DNA and the sequence organization of one family of clones, which contain sequences enriched in HeLa small polydisperse circular (spc) DNA, was studied by restriction mapping and base sequence analysis. Restriction mapping revealed each clone to be composed solely of imperfect tandem repeats of ca. 170 bp. The entire DNA sequence of one clone was determined and found to be alphoid satellite with a variant monomeric construction. PMID- 2582358 TI - Non-radioactive hybridization probes prepared by the chemical labelling of DNA and RNA with a novel reagent, photobiotin. AB - A photo-activatable analogue of biotin, N-(4-azido-2-nitrophenyl)-N'-(N-d biotinyl-3-aminopropyl)-N'-methyl-1,3- propanediamine (photobiotin), has been synthesized and used for the rapid and reliable preparation of large amounts of stable, non-radioactive, biotin-labelled DNA and RNA hybridization probes. Upon brief irradiation with visible light, photobiotin formed stable linkages with single- and double-stranded nucleic acids yielding probes which were purified from excess reagent by 2-butanol extraction and ethanol precipitation. Using single-stranded phage M13 DNA probes chemically labelled with one biotin per 100 400 residues and dot-blot hybridization reactions on nitrocellulose, as little as 0.5 pg (6 X 10(-18) mol) of target DNA was detected colorimetrically by avidin or streptavidin complexes with acid or alkaline phosphatase from three commercial sources. The sensitivity of detection of target RNA in dot-blots and Northern blots was equivalent to that obtained with 32p-labelled DNA probes. Photobiotin was also used for the labelling of proteins with biotin. PMID- 2582359 TI - Polymorphism in the structure of the yeast mitochondrial tRNA synthesis locus. AB - Yeast mitochondrial DNA contains a genetic locus, called the tRNA synthesis locus, which codes for information necessary for mitochondrial tRNA biosynthesis. A 9S RNA molecule coded by this locus is thought to be the trans-acting element required for the removal of 5' extensions from tRNA precursors. The DNA coding for this RNA maps to a region of mitochondrial DNA known to contain strain specific restriction site polymorphisms. Comparison of the tRNA synthesis locus in two such strains by sequence analysis demonstrates that the restriction enzyme polymorphisms are due to the deletion/insertion of a 50 base pair GC-rich element in the 5' flanking sequence of the 9S RNA coding region. There are also several differences between the 9S RNA coding region of these two strains which do not interfere with the tRNA synthesis function. PMID- 2582360 TI - Transcriptional and post-transcriptional regulation of storage protein gene expression in sulfur-deficient pea seeds. AB - We have used in vitro transcription in isolated pea nuclei to determine whether the expression of genes for the seed storage proteins legumin and vicilin is regulated transcriptionally or post-transcriptionally in response to changing sulfur status in the developing seed. During the first 48 h of recovery from S deficiency, transcription of legumin genes increased by two-fold whereas the level of legumin mRNA increased 20-fold in the same period. Vicilin gene transcription decreased during recovery, consistent with a gradual decrease in mRNA levels. We conclude that regulation of legumin mRNA levels in response to changing S status is post-transcriptional, whereas that of vicilin mRNA is transcriptional. In contrast, during normal plant development the expression of both of these gene families appears to be under transcriptional control. PMID- 2582361 TI - Comparison of the sequence specificity of bleomycin cleavage in two slightly different DNA sequences. AB - The sequence specificity of bleomycin damage was investigated utilising 340 bp alpha-DNA (a middle repetitive sequence in the human genome) as a target sequence. The following significant facts were found:- i) The dinucleotides GT and GC were cleaved on all occasions, GA most of the time, and AT, AC, GG and AA cleaved some of the time; ii) The base immediately 5' to the purine-pyrimidine dinucleotides was found to be statistically highly significant in determining the degree of damage caused by bleomycin, while other nearest neighbour bases had no significant effect; iii) The sequence specificity of bleomycin damage was determined on both strands and it was found that damage on either strand follows the above dinucleotide preference and is independent of the extent of damage on the opposite strand; iv) Bleomycin damage was compared between genomic 340 bp alpha-DNA and a cloned alpha-DNA with eleven base substitutions relative to the "consensus" sequence. There were forty-nine detectable differences in intensity of damage between these two DNA molecules. Although four of the differences can be directly attributed to changes in base sequence, the remaining differences were not at the base substitution sites. Some of the differences were over fifty base pairs from the nearest base substitution. We propose that the majority of these differences are due to microvariation in the structure of DNA with a slightly different DNA sequence. PMID- 2582362 TI - Spacer sequences downstream of the 28S RNA coding region are part of the mouse rDNA transcription unit. AB - Evidence is presented that more than 300 bp of spacer sequences downstream of the 28S RNA coding sequence are part of the mouse rDNA transcription unit. Studies in two cell-free transcription systems as well as analysis of cellular RNA indicate that RNA polymerase I does not terminate within the 334 bp 3' terminal spacer sequences contained in the rDNA clone used. Quantitative hybridization data, S1 mapping experiments and Northern analysis of nuclear RNA showed that the 14 kb pre-rRNA molecules hybridize with the same efficiency to both the 28S and the 3' NTS specific DNA probe. This indicates that the rRNA precursor contains both at the 5' and 3' end several hundreds bases of external transcribed spacer sequences which are eliminated in subsequent processing reactions. PMID- 2582363 TI - Rat alpha 1-fetoprotein messenger RNA: 5'-end sequence and glucocorticoid suppressed liver transcription in an improved nuclear run-off assay. AB - Cloned cDNA fragments spanning nearly the entire coding regions of rat AFP and albumin genes were used in liver nuclear run-off assays. Under standard assay conditions, transcription signals detected with 5' probes were systematically stronger than with 3' probes. Heparin eliminated this phenomenon, which suggests that nuclear run-off assays are subject to in vitro reinitiation occurring preferentially in promoter gene regions. Transcription in the presence of heparin indicates that very few polymerases are engaged on the AFP gene in adult rat liver. Dexamethasone treatment of developing rat liver results in the loss of transcribing polymerases from all regions of the AFP gene. Albumin gene transcription is unaffected. Inhibition of liver protein synthesis with cycloheximide does not modify the AFP gene suppressive action of dexamethasone. Glucocorticoid hormone receptors may thus directly interact with the AFP locus, blocking polymerase initiation. We also report the sequence analysis of rat AFP mRNA, which reveals the existence of two potential initiation codons on this molecule. PMID- 2582364 TI - Association of the lupus antigen La with a subset of U6 snRNA molecules. AB - U6 snRNA is a component of the major class of small RNA-protein complexes, the Sm snRNPs, present in mammalian cell nuclei. Here we report that a substantial fraction (about 10%) of U6 RNA from human and mouse cells is associated with another lupus antigen, the 50 kd La protein. The La-bound U6 subpopulation is characterized by 3' end heterogeneity and partial undermethylation. These U6 molecules have U-rich 3' termini that could be responsible for their selective association with the La protein. The question of whether they are precursors to the major U6 RNAs found in Sm snRNPs is discussed. PMID- 2582366 TI - A beta zero-thalassemic beta-globin RNA that is labile in bone marrow cells is relatively stable in HeLa cells. AB - We have shown previously that a beta-globin RNA-deficient beta zero-thalassemia is caused by a single base-pair deletion in codon 44 of the human beta-globin gene1. The lack of beta-globin RNA in erythroid cells of these affected individuals is due to extreme beta-globin RNA instability (t 1/2 = 30 min)2. We have further investigated the mechanism of this extreme lability by transiently expressing the beta zero-thalassemic allele in HeLa cells and assaying the stability of the beta-globin RNA that is produced. Surprisingly, the beta zero thalassemic RNA is much more stable in HeLa cells than in bone marrow cells. Apparently, developing erythroid cells have a mechanism for turning over this thalassemic RNA while cervical carcinoma cells do not. We also have assayed the stability of RNA derived from in vitro-mutagenized beta-globin genes. In HeLa cells, beta-globin RNAs harboring deletions in and around the translation initiation codon accumulate to steady-state levels that are similar to the level of normal beta-globin RNA. PMID- 2582365 TI - Analysis of cDNA and genomic clones coding for the pro alpha 1 chain of calf type II collagen. AB - A bovine cDNA library constructed from fetal cartilage RNA was screened with a pro alpha 1(II) collagen specific chicken cDNA. A recombinant clone (Bc 7), with an insert of 1 kb, was identified and shown to contain sequences exhibiting 85% homology with the chicken pro alpha 1(II) collagen C-propeptide. Interspecies comparison strongly suggested that one potential glycosylation site present in the avian C-propeptide is not utilized, since this site is absent in the bovine chain. In addition, two overlapping genomic clones (Pal 3 and Pal 4) were isolated and partially characterized. These clones span 23 kb of DNA and contain approximately 17 kb of the pro alpha 1(II) calf gene. Sequencing of exon 1 has determined the length of the 3' untranslated region and the exact location of the polyadenylation attachment site. PMID- 2582367 TI - Eleven new sequence variants of citrus exocortis viroid and the correlation of sequence with pathogenicity. AB - Full-length double-stranded cDNA was prepared from purified circular RNA of two new Australian field isolates of citrus exocortis viroid (CEV) using two synthetic oligodeoxynucleotide primers. The cDNA was then cloned into the phage vector M13mp9 for sequence analysis. Sequencing of nine cDNA clones of isolate CEV-DE30 and eleven cDNA clones of isolate CEV-J indicated that both isolates consisted of a mixture of viroid species and led to the discovery of eleven new sequence variants of CEV. These new variants, together with the six reported previously, form two classes of sequence which differ by a minimum of 26 nucleotides in a total of 370 to 375 residues. These two classes correlate with two biologically distinct groups when propagated on tomato plants where one produces severe symptoms and the other gives rise to mild symptoms. Two regions of the native structure of CEV, comprising 18% of the total residues, differ between the sequence variants of mild and severe isolates. Whether or not both of these regions are essential for the variation in pathogenicity has yet to be determined. PMID- 2582368 TI - Nomenclature for incompletely specified bases in nucleic acid sequences: recommendations 1984. PMID- 2582370 TI - Molecular cloning and characterization of a gene coding for methanol oxidase in Hansenula polymorpha. AB - The structural gene and the regulatory DNA sequence of the yeast Hansenula polymorpha methanol oxidase have been isolated. According to the nucleotide sequence data obtained, the structural gene encodes a 664 amino acids long protein, contains no intervening sequences, and the 5'- and 3'-non-coding region contains several sequences implicated in transcription initiation and termination in the yeast Saccharomyces cerevisiae. Although the methanol oxidase is translocated to the peroxisomes, no cleavable signal sequence was found at the N terminus of the protein. PMID- 2582369 TI - Structure of a processed gene of mouse cytoplasmic gamma-actin transposed into a BAM5 sequence: insertion has created 13 base-pair direct repeats. AB - We have cloned a processed gene related to cytoplasmic gamma-actin from a phage library of mouse brain DNA. The gene lacks introns, carries a poly(dA) tract of 19-base pairs at the 3' end and is flanked by 13-base-pair direct repeats. Southern blotting experiments indicated that this segment is embedded in highly repetitive and strongly methylated sequences. Direct comparison of the flanking sequences with those of mouse repetitive DNAs revealed that this processed gene is integrated into a BAM5 family, which is one of the repetitive sequences of the mouse genome. In addition, it was shown that the direct repeats were created by a duplication of the corresponding 13-bp stretch of the BAM5 DNA as a consequence of the integration of this segment. These results strongly suggest that the processed gamma-actin gene has been conveyed to this locus through a poly(A)+ RNA intermediate by a transposon-like mechanism. PMID- 2582372 TI - 57Co-bleomycin scintigraphy in staging of carcinoma of the cervix. AB - 65 patients with cervical cancer at various stages of the disease were studied scintigraphically after 57Co-bleomycin administration, active urine being flushed out from the bladder continuously. The patients were submitted to other auxiliary tests and the interpretation of scintigraphic images could thus be verified. Scintigraphic data were classified semiquantitatively by scoring in the range from zero to 5. Results were evaluated in terms of ROC-curves. This method of analysis permitted selection of cut-off levels for binary decisions that yielded satisfactory sensitivity and acceptable specificity of the test. PMID- 2582373 TI - [Interference factors in the in vivo diagnosis of the thyroid]. AB - Anamnestic iodine contamination and medication with thyroid drugs were registered in 260 patients of a clinical thyroid care unit and 200 patients of a thyroid doctor's office in the southern German endemic goiter region. We found in the university clinic 54% patients with interfering factors, 30% with iodine contamination and 20% with multiple interferences. In the physician's practice there were 18%, nearly all treated with thyroid hormone. The influence of those factors on thyroidal technetium uptake and the resulting restriction on its diagnostic value is discussed. PMID- 2582371 TI - Compilation of small RNA sequences. PMID- 2582375 TI - A child with low imperforate anus. PMID- 2582374 TI - Osteogenesis imperfecta. PMID- 2582376 TI - A suggested code for permanent cardiac pacing leads. PMID- 2582377 TI - Rate-responsive pacing: clinical experience. AB - Single chamber, rate-responsive pacing is emerging as a new modality in cardiac pacing and in the near future, dual chamber rate-responsive pacing may be the optimal solution for most pacemaker patients. In this report we describe our short- and long-term clinical experience with two different rate-responsive pacemakers: the RS4, an asynchronous atrial sensing ventricular pacemaker, and the TX-pacemaker, which senses the evoked QT after a ventricular paced beat, as an indicator of metabolic demand. Both systems use a single ventricular lead. Nine patients received RS4 and 10 patients received TX units. All of these patients had AV block and good ventricular function except for three patients with sinus node disease in the TX group. Between 1 and 3 months after implantation, a 24-hour Holter monitoring was performed, during which two maximal symptom-limited treadmill exercise tests (Bruce protocol) were conducted in VVI (70 bpm) and rate-responsive modes, in a random fashion. The mean follow-up was 25 months in RS4 group and 10 months in TX group. Significant improvements in patient exercise tolerance were found in the rate-responsive mode (9.0 vs. 6.6 METs in VVI) with similar results in both groups (RS4 and TX) despite higher ventricular pacing rates in the TX group (121 bpm vs. 102 bpm in RS4). An autolimited rate-responsive pacemaker-mediated tachycardia, induced by retrograde ventriculo-atrial conduction, was observed in a patient with an RS4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582378 TI - Unexpected coexistence of supraventricular and ventricular tachycardia in patients with syncope. AB - The incidence of multiple, inducible sustained arrhythmias during electrophysiologic studies is unknown. We have identified five patients who had several sustained tachycardias, some of which were not previously recognized clinically. Three patients had documented sustained supraventricular tachycardia (one of these also had nonsustained ventricular tachycardia) and two had documented sustained ventricular tachycardia. The clinically documented tachycardia was successfully reproduced in all cases; however, the three cases of supraventricular tachycardia also had sustained ventricular tachycardia initiated, and the two cases of ventricular tachycardia also had sustained supraventricular tachycardia, which had not previously been seen. The underlying common denominators for all five patients were poor left ventricular function due to ischemic heart disease and a history of syncope. In one case of clinical supraventricular tachycardia, the second sustained tachycardia appeared following drug therapy (procainamide), which seemed to convert nonsustained to sustained ventricular tachycardia. In another patient with clinical ventricular tachycardia, the supraventricular tachycardia was also initiated following drug therapy (indecainide). We conclude that: (1) patients with syncope may have multiple arrhythmic etiologies and (2) complete electrophysiologic evaluation, during control studies as well as serial drug studies, are important in the management of these patients. PMID- 2582379 TI - Electrophysiologic study of tachycardia-dependent paroxysmal His bundle block in man. AB - Electrophysiologic study was performed in a patient with tachycardia-dependent paroxysmal atrioventricular block. The site of block was within the His bundle. The effective refractory period of the His bundle was markedly prolonged and it was comparable to the critical atrial cycle length producing type II His bundle block. The most likely mechanism of paroxysmal atrioventricular block was repetitive concealed penetration of the blocking zone by nonconducted impulses that reached the proximal His bundle. Enhancing the blocking ratio at the atrioventricular nodal level resulted in improvement of overall atrioventricular conduction. PMID- 2582380 TI - Amplitude of atrial electrical activity during sinus rhythm and during atrial flutter-fibrillation. AB - The onset of atrial flutter or fibrillation in a patient with a DDD pacemaker may result in sensing of the atrial arrhythmia and an inappropriate ventricular pacing response. In order to assess the potential of this problem, we evaluated the amplitude of atrial electrograms recorded from the right atrial appendage during sinus rhythm and during atrial flutter or fibrillation during 19 episodes in 18 patients. In 11 episodes of fibrillation and eight episodes of flutter, there was no difference in amplitude of either unipolar or bipolar atrial electrograms compared to that recorded during sinus rhythm (p greater than 0.05). In 14 of 19 episodes, the direction of depolarization of the bipolar electrogram did not change appreciably between sinus rhythm and the atrial arrhythmia. In summary, there is insufficient difference between amplitude of atrial depolarizations recorded during sinus rhythm and atrial flutter or fibrillation to be differentiated reliably by DDD pacemakers. PMID- 2582381 TI - Mixed carotid sinus hypersensitivity: successful therapy with pacing, ephedrine, and propranolol. AB - Three forms of carotid sinus hypersensitivity are recognized clinically (cardio inhibitory, vasodepressor, and mixed). The cardio-inhibitory form has been managed successfully with pacemaker therapy. The vasodepressor element has been difficult to manage clinically whether in its pure form or in combination with the cardio-inhibitory type. We review the various pharmacologic methods previously reported and present our experience with a new pharmacologic alternative, which is the combined use of ephedrine and propranolol to induce unopposed alpha stimulation. PMID- 2582383 TI - Electrocardiographic patterns resulting from improper connections of the right leg (ground) cable. AB - The patterns resulting from improper connections of the right leg (ground) cable to the right arm, left arm, and left leg electrodes (hardly ever discussed in books dealing with electrocardiography) are presented and their genesis is explained. Knowledge about this technical error is important because it: (1) may be misinterpreted as resulting from switching the right arm and left arm cables; and, worse, (2) may not be recognized, which, in patients with abnormal electrocardiograms, can lead to clinically significant errors in interpretation. PMID- 2582382 TI - Extreme intracardiac coiling of a transvenous pacemaker: a case report. AB - We report an unusual complication of transvenous pacing: extreme coiling of a pacemaker catheter, which formed a redundant, twisted loop protruding into the right ventricular outflow tract. This may be a result of "twiddling" (rotation) of the pacemaker generator by the patient and/or inadequate fixation of the catheter at the venous entry site. Careful fixation of the generator to the venous entry site within the subcutaneous pocket may prevent such a complication. PMID- 2582384 TI - Drug-device interactions: clinical considerations. PMID- 2582385 TI - Esophageal P-synchronous pacing. AB - An esophageal electrode can be employed to provide atrial sensing which then can be used to change from temporary right ventricular (VVI) pacing to P-synchronous (VAT) pacing. Two cases of postoperative aortic valve replacement, each with new complete heart block (CHB) and dopamine dependency, are presented. In both cases, establishment of P-synchronous pacing resulted in improved hemodynamic status characterized by successful weaning from dopamine and maintenance of adequate cardiac output (CO). PMID- 2582386 TI - Rate-responsive ventricular pacing: clinical experience with the RS4-SRT pacing system. AB - Eighteen patients (11 men and 7 women) with symptomatic second or third degree atrioventricular block underwent implantation of the rate-responsive RS4-SRT pacing system. Exercise tolerance in RS4 mode was compared to that in VVI mode by randomized double-blind treadmill stress testing. Following hospital discharge, RS4 function was assessed by repeat exercise testing and 24-hour Holter monitoring. Difficulty in obtaining satisfactory P-wave amplitudes at implantation (mean 3.1 +/- 1.5 mV) resulted in prolonged implantation times (mean 79.4 +/- 26.4 minutes). Following implantation, 10 patients (58%) showed a significant ventricular rate response to exercise, seven did not, and one remained in sinus rhythm. For responders, peak ventricular paced rate and double product were significantly greater in RS4 than in VVI mode, being 101.8 +/- 5.8 vs. 74.3 +/- 0.4 beats per minute and 20.1 +/- 2.9 vs. 15.5 +/- 3.7 beats per minute X mmHg X 10(-3), respectively (p less than 0.001). However, treadmill times (10.5 +/- 2.6 vs. 9.7 +/- 3.3 minutes) and work done (5.51 +/- 2.01 vs. 4.97 +/- 2.33 joules X 10(-5] were not significantly different (p = 0.22). Following hospital discharge, repeat exercise testing and 24-hour Holter monitoring demonstrated RS4 function in 11 of 16 and 15 of 18 patients, respectively. We conclude that, due to unreliable atrial sensing, the RS4-SRT pacing system does not provide the reliable rate-responsiveness required to improve exercise tolerance. PMID- 2582387 TI - Reappearance of persistent normal sinus rhythm in a patient with the sick sinus syndrome following cardiac pacing for 10.5 years. AB - A patient with symptomatic sick sinus syndrome which manifested as a brady-tachy syndrome, was admitted to our institute in 1969. Following cardiac pacing for 10.5 years, the brady-tachy syndrome disappeared and normal sinus rhythm was restored. Her stable normal sinus rate has persisted up to the present, 2.5 years after termination of pacing. PMID- 2582388 TI - Atrioventricular conduction abnormalities in patients undergoing isolated aortic or mitral valve replacement. AB - Cardiac conduction defects are common in patients with aortic valve disease. Several studies have suggested that the spontaneous occurrence of complete heart block in these patients is related to the extent of calcium deposits in the aortic valve and adjacent structures. No studies have been done to relate the occurrence of complete heart block at the time of valve replacement to predictive factors. We evaluated 102 consecutive patients undergoing isolated aortic valve replacement and 100 patients undergoing isolated mitral valve replacement. Although transient complete heart block was relatively common in each group (17.6% and 13%, respectively), we were not able to identify any factors predictive of its occurrence. There was a very low incidence of late heart block in a follow-up period of over four years. Thus, the capability for temporary pacing is mandatory in patients undergoing valve replacement. However, transient complete AV block during the perioperative period does not predict late recurrence of AV block and, therefore, prophylactic pacemaker or electrode implantation during or following transient block appears unnecessary. PMID- 2582389 TI - Atrial and ventricular burst pacing from a coronary sinus catheter: relation to position of radiofrequency transmitter. AB - A young woman with drug-refractory recurrent supraventricular tachycardia was managed by rapid atrial stimulation using a catheter positioned in the coronary sinus. During follow-up, radiofrequency activation of the pacemaker resulted in burst ventricular and/or atrial pacing, depending on the distance of the transmitter's antenna loop from the receiver. Current output was directly related to the distance of the transmitter's antenna loop from the receiver and ranged from 20 mA at a distance of 0 cm from the receiver to 1 mA at 5 cm. If possible, coronary sinus lead placement should be avoided for radiofrequency-activated atrial burst pacing given the large current output with direct contact of the transmitter's antenna loop to the implanted receiver and the risk for ventricular stimulation. Alteration of the spatial relationship between the transmitter and receiver can be used to decrease current output and prevent ventricular pacing if atrial burst pacing from the coronary sinus is desirable. PMID- 2582390 TI - Atrial pacing bigeminy: a manifestation of crosstalk. AB - Atrial pacing bigeminy, defined as atrial pacing with alternating short and long cycle lengths, was recorded in two out of five DDD-pacemaker implants. Another fascinating feature, the lowering of the effective pacing rate after programming to a higher rate, occurred in one patient. Both phenomena can be explained by crosstalk; appropriate programming resulted in normal DDD-function in all cases. These observations in our patients have led to some interesting conclusions regarding multiprogrammability and nominal settings. PMID- 2582391 TI - Radionuclide evaluation of dual chamber pacing: comparison between variable AV intervals and ventricular pacing. AB - We prospectively evaluated changes in left ventricular ejection fraction, end diastolic volume, and stroke volume via radionuclide multigated acquisition study. Comparison was made between ventricular pacing and dual chamber pacing with varying AV intervals. The volumes and changes in ejection fraction were determined at rest, at set increased pacing rates, and during physiological stress. AV sequential pacing shows overall improvement in cardiac function in the majority of patients regardless of left ventricular function. The shorter AV interval would be appropriate for the majority of patients who have an atrial tracking mechanism (adequate intrinsic sensed atrial activity followed by ventricular pacing) and who undergo significant physiological stress. PMID- 2582392 TI - Artificial circus movement tachycardias: incidence, mechanisms, and prevention. AB - In a group of 45 patients treated with Medtronic 7000 and 7100 pulse generators for sick sinus syndrome or second or third degree atrioventricular block, an atrial synchronous mode of pacing was programmed in 34 cases and spontaneously occurring artificial circus movement tachycardias (ACMTs) were observed in nine. An analysis of conditions of occurrence, triggering mechanisms and patterns of ACMT, is presented. Various modalities of prevention are discussed. They resulted in suppression of ACMT in five patients and decrease of incidence in a sixth; the three remaining subjects were managed by definitive reprogramming in the DVI mode. Our conclusion is that correct prevention of ACMT requires the use of dual chamber pulse generators with programmable atrial refractory periods. For patients in whom a unit has already been implanted, careful observation of the triggering mechanism and pattern of ACMT may help in determining the most suitable way to prevent and suppress the arrhythmia. PMID- 2582393 TI - The role of electrophysiologic studies in the management of patients with unexplained syncope. AB - We evaluated the frequency and type of electrophysiologic abnormalities in an unselected population of consecutive patients with unexplained syncope. Fifty patients were entered in the study; all had 24-hour dynamic electrocardiographic (Holter) recordings and underwent complete electrophysiological studies. An abnormal electrophysiologic study was found in 74% of the patients. Sinus node abnormality was observed in 30%, abnormal AV node function in 14%, long HV in 10%, block distal to H during rapid atrial pacing in 6%, paroxysmal supraventricular tachycardia in 12%, ventricular tachycardia/fibrillation in 8%, and hypersensitive carotid sinus syndrome in 24%. There was no correlation between Holter and electrophysiologic study findings except for the presence of paroxysmal sustained supraventricular tachycardia. Based on clinical, Holter monitoring, and electrophysiologic findings, 38% were treated by antiarrhythmic drugs, 40% received permanent pacemakers, and 22% were not treated at all. During follow-up (23 +/- 13 months), 9 patients (18%) experienced recurrent syncope or death. PMID- 2582394 TI - Pacemaker-mediated tachycardia initiated by coincident P-wave undersensing and ventricular blanking period. AB - Pacemaker-mediated tachycardias (PMT) have received much recent attention. We describe the course and treatment of a 60-year-old man with an AV universal (DDD) pacemaker who developed a pacemaker-mediated tachycardia. The tachycardia was initiated by the coincidence of an unsensed P-wave, a QRS that was also not sensed due to the ventricular blanking period, and a short right ventricular myocardial effective refractory period. Treatment consisted of reprogramming the atrial sensitivity of the device. Physicians should be aware of the potential for the ventricular blanking period to participate in the initiation of pacemaker mediated tachycardias. PMID- 2582395 TI - Late potentials and arrhythmogenesis. AB - There are three current prognostic indicators of ventricular electrical instability: categorization and stratification of spontaneous ventricular arrhythmias from standard ECG recordings; programmed electrical stimulation; direct recording of delayed depolarization potentials, usually referred to as late potentials. Of the three, the latter offers a new and promising approach. Late potentials represent delayed activation potentials of diseased myocardial zones and may prove to be a strong independent marker of the propensity to develop reentrant ventricular arrhythmias and sudden cardiac electrical death. The problem in identifying late potentials on the body surface is that the signal is smaller than the electrical noise produced by various sources. Two different techniques have been utilized to improve the signal-to-noise ratio: first, signal averaging, which is applicable to regular repetitive electrocardiographic signals but cannot detect moment-to-moment dynamic changes in the signal; second, low noise or high-resolution electrocardiography that utilizes spatial averaging techniques as well as other noise-reducing measures to record the late potentials on a beat-to-beat basis. This technique has the potential of directly identifying malignant "reentrant" versus benign "focal" ventricular rhythms. The present report discusses the electrophysiologic basis of late potentials and the clinical results of both signal-averaged and low-noise recordings for evaluation of ventricular electrical instability, particularly in patients with ischemic heart disease. PMID- 2582396 TI - Electrophysiological testing of sinus node function. PMID- 2582397 TI - Primary cardiac amyloidosis treated with permanent pacing. PMID- 2582398 TI - Polymorphous ventricular tachycardia (PVT) PMID- 2582400 TI - 3rd European Symposium on Cardiac Pacing. Torremolinos, Malaga, Spain, June 2-5, 1985. Abstracts. PMID- 2582399 TI - Product-oriented research. PMID- 2582402 TI - [Clinical value of the analysis of amylase isoenzymes in the blood and urine of patients wih cholelithiasis without acute pancreatitis]. PMID- 2582401 TI - Amsacrine (m-AMSA): a new antineoplastic agent. Pharmacology, clinical activity and toxicity. AB - The synthetic aminoacridine derivative amsacrine (m-AMSA) is capable of preventing DNA from serving as a template in replication and DNA synthesis. This mechanism of action is similar to that of anthracyclines, but clinical evidence suggests the lack of cross-resistance. The recommended dosage in patients with solid tumors is 90-120 mg/m2 intravenously every 3-4 weeks. Despite the initial encouraging reports from experimental models, m-AMSA has shown no real impact in the treatment of patients with a wide variety of solid tumors. In relapsed acute nonlymphocytic leukemia, 20-30% of patients will achieve complete remission. An increased remission rate is obtained when m-AMSA is combined with other agents, especially with high-dose cytosine arabinoside, with a complete remission rate of 50-60% in relapsed patients. Currently, several phase III trials are evaluating m AMSA combinations against daunorubicin-containing regimens in patients with previously untreated acute leukemia. The potential role of these regimens in this disease remains to be defined. PMID- 2582403 TI - Tissue mast cells in health and disease. AB - Mast cells (MC) are regular constituents of soft tissue and occur with varying frequency in nearly every organ. They derive from monocytic cells occurring in the adhering mononuclear fraction of the peripheral blood. Their subsequent evolution into mature MCs is primed by a MC generating lymphokine released by sensitized T-cells on restimulation by the antigen. MC granules contain preformed heparin histamine and eosinophil chemotactic factors. Other factors such as leukotriene B4 can be produced by MCs following stimulation. This is the case during the initial phase of nonspecific inflammations, when MCs are stimulated by complement activation. In the immediate type hypersensitivity reaction giving rise to IgE, MC degranulation occurs independent from complement. In IgG and IgM mediated reactions, however, MC involvement is effected by complement consumption and C5 a generation. In delayed type hypersensitivity MCs increase locally. Their functional significance remains obscure. MC neoplasias are rare and generally confined to the dermis. Cutaneous mastocytoses are called benign mastocytoma when localized and urticaria pigmentosa when disseminated. Generalized mastocytosis involves extracutaneous tissue irrespective of skin involvement. Those associated with urticaria pigmentosa-like skin lesions, present at the onset of the disease, have a significantly higher survival rate than those lacking a primary skin involvement. The term urticaria pigmentosa should be reserved for cases of cutaneous mastocytosis without extracutaneous involvement. Cases of mastocytoses lacking primary skin lesions assume a malignant course and are additionally aggravated by high incidence of myeloproliferative disorders and MC leukemia. MC sarcoma is an extremely rare neoplasia of MCs which may also terminate as a MC leukemia. PMID- 2582404 TI - Effects of aphidicolin and alpha-amanitin on visualization of acridine orange binding to DNA in rat astrocytoma C6 cells. AB - The purpose of this study was to examine effects of aphidicolin and alpha amanitin on visualization of acridine orange (AO) binding to DNA in rat astrocytoma C6 cells and to discuss briefly the significance of AO chromatin interaction products. Aphidicolin inhibited DNA synthesis but percentage of AO positive cells was approximately 60% of that of the untreated control cells. alpha-Amanitin caused a slight inhibition of RNA synthesis and 3H-uridine incorporation in the treated cells was about 64% of that of the untreated cells, whereas a distinct decrease of the number of AO positive cell nuclei was observed. The results suggest that activity of RNA polymerase II and mRNA synthesis is mainly concerned in visualization of AO chromatin interaction products. PMID- 2582405 TI - [Detection of hyperamylasuria. Value of a quick test]. AB - A new reactive strip was used in a hospital admission unit, to detect amylasuria in the urine of 76 patients consulting for abdominal pain (population A) and of 68 unselected patients (population B). Detection on admission by this method was concordant with subsequent laboratory detection in 93% of the cases. The fast test was positive for amylasuria in 17 patients: 13 (17.1%) in population A and 4 (5.9%) in population B. The 8 patients recorded as "+" had moderate amylasuria with multiple but ill-defined symptoms mostly abdominal. The 9 patients recorded as "++" had marked amylasuria highly suggestive of an abdominal disease, including 4 cases of chronic pancreatitis. PMID- 2582406 TI - [Is urography necessary in the preoperative exploration of prostatic adenoma?]. PMID- 2582408 TI - Endonuclease-resistant apyrimidinic sites formed by neocarzinostatin at cytosine residues in DNA: evidence for a possible role in mutagenesis. AB - When defined-sequence DNA from the lacl region of plasmid pMC1 was treated with the nonprotein chromophore of neocarzinostatin in the presence of various thiols, the predominant lesions were direct strand breaks, occurring primarily at thymine and adenine residues. In the presence of glutathione, however, alkali-dependent strand breaks, occurring at certain cytosine residues, were also detected but were virtually absent when other thiols were used. Chromophore-induced release of free cytosine base from [3H]cytosine-labeled DNA was 2- to 3-fold greater with glutathione than with the other thiols. These results suggest that the alkali dependent strand break is some form of apyrimidinic site. These sites were substrates for endonuclease IV of Escherichia coli, although a 5-fold greater concentration of enzyme was required for their cleavage than was required for cleavage of apurinic sites in depurinated DNA. These sites were also less sensitive to E. coli endonuclease VI (exonuclease III) by a factor of at least 5 and less sensitive to E. coli endonuclease III by a factor of at least 10. These and other results suggest that these sites are chemically different from normal apurinic/apyrimidine sites. When chromophore-induced apyrimidinic sites were quantitated as alkali-dependent breaks at 11 specific sites in the lacl gene, a correlation was found between occurrences of these lesions and the reported frequencies of G-C to A X T transitions at the same sites. All occurrences of the trinucleotide sequence A-G-C, including the ochre 21 mutational hot spot, were particularly prominent sites. The selective formation of endonuclease-resistant apyrimidinic sites at specific cytosine residues may explain the high frequency of G X C to A X T transitions in the mutational spectrum of neocarzinostatin. PMID- 2582409 TI - Defective macromolecule biosynthesis and cell-cycle progression in a mammalian cell starved for mevalonate. AB - The isolation of a somatic cell mutant (Mev-1) with a block in one of the mevalonate-biosynthesizing enzymes (3-hydroxy-3-methylglutaryl-coenzyme A synthase, EC 4.1.3.5) has afforded us the opportunity to test and to extend the hypothesis that a product of mevalonate biosynthesis other than cholesterol is required for cellular proliferation. We present evidence here that both DNA synthesis and protein synthesis are inhibited in this mutant by mevalonate starvation, although RNA synthesis appears to be unaffected. The loss of DNA synthesis and the loss of protein synthesis in this mutant appear to be due to independent processes. DNA synthesis is reversibly inhibited by mevalonate starvation at a unique point in the cell cycle. Resumption of DNA synthesis after readdition of mevalonate exhibits a long lag; the peak of S-phase DNA synthesis occurs approximately 17 hr after mevalonate readdition, suggesting that mevalonate starvation puts cells into a quiescent (G0) state owing to their failure to transit a restriction point. The loss of DNA biosynthesis in the Mev-1 cell is well correlated with the rate of turnover of mevalonate label of certain terpenylated polypeptides. PMID- 2582407 TI - Complete nucleotide sequence of an infectious clone of human T-cell leukemia virus type II: an open reading frame for the protease gene. AB - The entire nucleotide sequence of an infectious clone of human T-cell leukemia virus type II provirus was determined. This provirus consists of 8952 nucleotides. In addition to long terminal repeats and gag, pol, env, and X, a protease gene that is responsible for processing the gag precursor protein was found. The protease gene is encoded in a different frame from gag and pol and was located between the gag and pol open reading frames. The 5' region of the protease gene overlaps the 3' gag region. Coding regions of the provirus show about 60% homology with those of human T-cell leukemia virus type I at the nucleotide level. The evolutionary relationship between human T-cell leukemia virus types I and II is discussed. PMID- 2582410 TI - Cell-type-specific receptors for alpha-fetoprotein in a mouse T-lymphoma cell line. AB - Binding and uptake of alpha-fetoprotein (AFP) by mouse T-lymphoma YAC-1 cells exhibited the characteristics of receptor-mediated endocytosis. The binding saturation curve obtained by incubating YAC-1 cells at 4 degrees C with 125I labeled AFP at different concentrations (50 ng/ml to 2.5 mg/ml) showed three saturation plateaus. AFP binding was inhibited by unlabeled mouse, rat, or bovine AFP and, to a lesser extent, by rat or bovine serum albumin. No significant competition was observed with transferrin, alpha 2-macroglobulin, IgG, or ovalbumin. Scatchard analysis suggested the presence of three types of receptor sites with a Kd of 2.2 X 10(-9) M (approximately equal to 700 sites per cell), 8.6 X 10(-7) M (approximately equal to 210,000 sites per cell), and 5.7 X 10(-6) M (approximately equal to 910,000 sites per cell), respectively. At 37 degrees C, AFP was rapidly internalized and could be localized in the cytoplasm after incubation of cells with fluoresceinated AFP. After a short residence time, AFP was released undegraded from the cells. Normal adult thymocytes and T lymphocytes, which are counterparts of YAC-1 cells, did not show any significant uptake of AFP. On the other hand, a small subpopulation of fetal and newborn thymocytes was labeled by fluoresceinated AFP. PMID- 2582411 TI - Human T-lymphocyte response in vitro to synthetic peptides of herpes simplex virus glycoprotein D. AB - Immunization of mice with a synthetic peptide that corresponds to a murine antibody-defined immunodominant domain of herpes simplex virus (HSV) glycoprotein D (gD) induced neutralizing antibodies against HSV types 1 and 2 and protected animals against a lethal challenge with HSV type 2 (Dietzschold, B., Eisenberg, R., Ponce de Leon, M., Golub, E., Hudecz, F., Varicchio, A. & Cohen, G. (1984) J. Virol. 52, 431-435). We report here that human peripheral blood T cells from HSV seropositive and -seronegative adult donors are activated by this synthetic peptide in vitro. Interleukin-2-dependent T-cell lines established from these cultures respond specifically to peptides containing residues 1-23 of HSV gD and to a panel of overlapping peptides within this domain. The T-cell proliferative response was maximal when the majority of interleukin-2-propagated T cells were of the helper phenotype and the peptides were at least 16 amino acids long. Peptides of 8 or 12 amino acids from the carboxyl terminus were nonstimulatory. Peptide-activated T-cell lines from sero-negative donors less than 11 years old could be established in vitro, but most cells were of the suppressor/cytotoxic phenotype and demonstrated no antigen-specificity when tested with the panel of synthetic peptides. PMID- 2582413 TI - A monoclonal antibody against human thrombospondin inhibits platelet aggregation. AB - A monoclonal antibody (C6.7) has been generated against the calcium-replete form of human platelet thrombospondin (TSP). C6.7 is specific for TSP as determined by both competitive radioimmunoassay and immunoprecipitation. This antibody inhibits both thrombin- and A23187-induced aggregation of gel-filtered platelets in a concentration-dependent manner without affecting the secretion of serotonin. The epitope on TSP recognized by C6.7 has been localized to an 18-kDa fragment that is present in mild chymotryptic digests of TSP. This fragment is disulfide-linked to a 120- to 140-kDa fragment in unreduced digests, and both reduction and denaturation are required to separate the 18-kDa peptide from the larger fragments. A 25-kDa heparin binding domain is also present in the chymotryptic digest. However, the 18-kDa peptide is distinct from the heparin binding domain. The amino acid sequence at the NH2 terminus of the 18-kDa fragment is Asp-Thr-Asn Pro-Thr-Arg-Ala-Gln-Gly-Tyr-. PMID- 2582412 TI - Isolation and characterization of an RNA-proteolipid complex associated with the malignant state in humans. AB - An RNA-proteolipid complex was isolated from sera of patients with a variety of malignant disorders as well as from culture media of malignant cell lines. The complex, characterized by a relatively constant composition, contains 27S poly(A)+ RNA and Mr 1250 oligopeptide(s) and is rich in phospholipids and glycosphingolipids. Serum lipoproteins (low and high density) differ from this complex in density, chemical composition, and immunological reactivity. The complex was detected in 94 of 96 cases of malignancy tested but not in any of 58 patients with nonmalignant disorders or in 46 healthy individuals. PMID- 2582414 TI - Immunological properties of the Gag protein p24 of the acquired immunodeficiency syndrome retrovirus (human T-cell leukemia virus type III). AB - Antigenic cross-reactivity of human T-cell leukemia virus type III (HTLV-III) with HTLV-I and HTLV-II and other retroviruses was measured by using a stringent homologous competition radioimmunoassay for the Gag protein p24 and a less stringent electrophoretic transfer blot assay. In the competition radioimmunoassay only minimal cross-reactivities were detected between HTLV-III p24 and both HTLV-I and HTLV-II. No cross-reactivity was detected with any other retrovirus. In the electrophoretic transfer blot system using rabbit antibody to HTLV-I, HTLV-II, and HTLV-III, low-level cross-reaction was detected between HTLV I and HTLV-III and between HTLV-II and HTLV-III. Unlike the cross-reactivity between HTLV-I p24 and HTLV-III p24, which was bidirectional, the one between HTLV-II and HTLV-III was only a one-way reactivity. Antiserum to HTLV-II recognized HTLV-III p24, but the antiserum to HTLV-III did not recognize HTLV-II p24. The results indicate that HTLV-III is a unique retrovirus with a limited homology with HTLV-I and HTLV-II but unrelated to most other retroviruses. PMID- 2582415 TI - The 200- and 150-kDa neurofilament proteins react with IgG autoantibodies from patients with kuru, Creutzfeldt-Jakob disease, and other neurologic diseases. AB - Sera from 65 patients with spongiform virus encephalopathies (29 with kuru, 36 with Creutzfeldt-Jakob disease), 79 with other neurologic diseases, and 65 control subjects were examined for reactivity in immunoblots of preparations of myelinated axons and neurofilaments from mouse brain. The sera reacted most frequently with the 200-kDa and 150-kDa neurofilament proteins and less frequently with the 70-kDa neurofilament protein and a 62-kDa neurofilament associated protein. The sera reacted with the same proteins as those which reacted with rabbit and mouse polyclonal antibodies and mouse monoclonal antibody to neurofilament proteins. Serum reactions were also seen with Trixon X-100 extracts of chimpanzee brain and bovine spinal cord but not with Triton extracts of liver, kidney, and muscle. PMID- 2582417 TI - Evidence that receptors mediating central synaptic potentials extend beyond the postsynaptic density. AB - Physiological recordings and computer simulations of unitary inhibitory postsynaptic potentials in the Mauthner cell of the goldfish central nervous system have been used to estimate the expected size of the postsynaptic receptor matrix at individual junctions. Simultaneous pre- and postsynaptic recordings were used to determine the kinetic parameters of the quantal responses under normal conditions and in the presence of strychnine, a competitive antagonist of glycine, which is the putative transmitter at these synapses. Calculations indicate that if the postsynaptic density, which has a radius of 0.1 micron, were to accommodate the population of channels estimated to be opened during a quantal response, the glycine binding site density in that region would be unrealistically high. Computer simulation of the quantal responses included transmitter diffusion, transmitter-receptor interactions, and channel activation under conditions including both normal and lowered binding site densities, the latter corresponding to the experimental data obtained with strychnine. The data indicate that the synaptic receptors involved in generating unitary responses are widely distributed to include regions located outside the junctional area, which directly faces the presynaptic release sites. We further suggest that the receptor matrix is surrounded by a restricted diffusional space; this geometrical organization may underlie the finding that response rise times are relatively independent of receptor binding site densities. PMID- 2582418 TI - Batrachotoxin changes the properties of the muscarinic receptor in rat brain and heart: possible interaction(s) between muscarinic receptors and sodium channels. AB - The effects of Na+-channel activator batrachotoxin (BTX) on the binding properties of muscarinic receptors in homogenates of rat brain and heart were studied. BTX enhanced the affinity for the binding of the agonists carbamoylcholine and acetylcholine to the muscarinic receptors in brainstem and ventricle, but not in the cerebral cortex. Analysis of the data according to a two-site model for agonist binding indicated that the effect of BTX was to increase the affinity of the agonists to the high-affinity site. Guanyl nucleotides, known to induce interconversion of high-affinity agonist binding sites to the low-affinity state, canceled the effect of BTX on carbamoylcholine and acetylcholine binding. BTX had no effect on the binding of the agonist oxotremorine or on the binding of the antagonist [3H]-N-methyl-4-piperidyl benzilate. The local anesthetics dibucaine and tetracaine antagonized the effect of BTX on the binding of muscarinic agonists at concentrations known to inhibit the activation of Na+ channels by BTX. On the basis of these findings, we propose that in specific tissues the muscarinic receptors may interact with the BTX binding site (Na+ channels). PMID- 2582416 TI - Antibodies to synthetic peptides as probes for the binding site on the alpha subunit of the acetylcholine receptor. AB - Synthetic peptides and their respective antibodies were used in an attempt to localize and identify the ligand-binding site of the nicotinic acetylcholine receptor. Two peptides of the receptor alpha subunit were synthesized, the first corresponding to the NH2-terminal domain (positions 1-20) and the other, to a segment (residues 126-143) that contains the first two cysteine residues. Specific antipeptide antibodies were elicited in rabbits after immunization with the peptides conjugated to bovine serum albumin. The antipeptide antibodies thus obtained cross-reacted with the receptor and bound specifically to its alpha subunit. The antipeptide antibodies were used to test whether the peptide sequences corresponded to the alpha-bungarotoxin (alpha-BTX)-binding site. Staphylococcus aureus V8-protease digestion of the isolated receptor alpha subunit generated several fragments. Antipeptide (1-20) and antipeptide (126-143) both bound a 26-kDa fragment, whereas only antipeptide (126-143) bound a 17-kDa fragment. None of these fragments were found to bind alpha-BTX. On the other hand, alpha-BTX bound to an 18-kDa fragment that did not react with either of the antipeptide antibodies. Moreover, the 26-kDa and 17-kDa fragments were also found to contain the endoglycosidase H-susceptible oligosaccharide chain. Our results indicate that the toxin-binding site lies beyond the first possible V8 protease cleavage site after residues 126-143: i.e., Asp-152. This location is in agreement with the possibility that cysteine residues 192 and/or 193 are in close proximity to or contiguous with the ligand-binding site. PMID- 2582419 TI - Characterization of Lewis antigens in normal colon and gastrointestinal adenocarcinomas. AB - The Lewis a antigen (Lea)- and Lewis b antigen (Leb)-active glycolipids and glycoproteins in normal colon mucosa, colon carcinoma tumors, and gastrointestinal tumor cell lines were studied by using monoclonal antibodies against Lewis determinants in solid-phase radioimmunoassay, chromatogram binding assay, and immunoprecipitation/PAGE. Lea-5 was a major component of the purified non-acid glycolipid fraction from normal colon mucosas from four patients examined and Lea-7 was a minor component in three of these four cases. Lea in colon carcinoma of the same patients was expressed as Lea-5 in all four cases and as both Lea-5 and Lea-7 in one of the four cases. All normal colon mucosa samples expressed Lea but not Leb. Leb-6 was expressed in all tumors obtained from the same patients as normal colon mucosa (Leb negative) samples and in the gastrointestinal tumor cell lines. These findings indicate that Leb is a colon adenocarcinoma-associated antigen and that Lea and Leb are coexpressed in tumor tissue. Evidence is presented for the coexistence of Lea and Leb carbohydrate determinants in both glycolipid and glycoprotein forms in the same cells. PMID- 2582420 TI - Characterization of an almost full-length cDNA coding for human blood coagulation factor X. AB - A human liver cDNA library was screened by colony hybridization with a bovine factor X cDNA probe. Three of the positive plasmids contained overlapping DNA that coded for most of human factor X mRNA. DNA sequence analysis of these three clones allowed the prediction of the complete amino acid sequence of plasma factor X. From these studies, we predict that human factor X is synthesized as a single polypeptide chain precursor in which the light and heavy chains of plasma factor X are linked by the tripeptide Arg-Lys-Arg. The cDNA sequence also predicts that human factor X is synthesized as a preproprotein having an amino terminal leader peptide of at least 28 amino acid residues. A comparison of the amino acid sequences of human and bovine factor X shows high sequence identity around the calcium-binding regions and catalytic regions but low sequence identity around the nonfunctional regions. PMID- 2582421 TI - Synthesis of small nuclear ribonucleoprotein particles by the malarial parasite Plasmodium falciparum. AB - Sera from patients with autoimmune diseases have been used to identify small nuclear ribonucleoprotein particles (snRNPs) present in higher eukaryotic cells and also in dinoflagellates. Previously these sera have not detected crossreactive snRNP protein antigens of other lower eukaryotes such as yeast, Tetrahymena, or Dictyostelium. We report that anti-Sm, anti-U1-RNP, and anti La/SS-B human antisera react with specific snRNP protein antigens synthesized by the protozoan Plasmodium falciparum, the human malarial parasite. These results suggest that the structure and antigenicity (and thus probably the function) of snRNPs have been widely conserved in eukaryote evolution. PMID- 2582423 TI - N-myc amplification in multiple homogeneously staining regions in two human neuroblastomas. AB - Molecular characterization of two human neuroblastoma cell lines has revealed that both contain multiple homogeneously staining regions (HSRs), each representing a chromosome site of N-myc amplification. The newly established cell line CHP-382/JK had two cytogenetically distinct populations with several identical chromosomal abnormalities, indicating a common progenitor cell. Each population had one HSR, one on chromosome 5 at q31-34 and the other on chromosome 2 at q31-32. Chromosomal in situ hybridization with the N-myc probe pNb-1 demonstrated that both HSRs contained amplified copies of N-myc. Southern blot analysis confirmed amplification of N-myc sequences in genomic DNA of CHP-382/JK. Chromosomal features of CHP-382/JK shared with other neuroblastoma cell lines were the deletion of 1p and the presence of extra 17q material. In addition, the cells were highly reactive to monoclonal antibody PI 153/3 used to identify human neuroblastoma. CHP-382/JK cells were further characterized as neuronal cells by the expression of neurotoxin-responsive Na+ channels. Another neuroblastoma cell line, CHP-134, contained a single cell population with three HSRs, one in the short arm of each chromosome 7 and one in the long arm of a chromosome 6. All three HSRs contained amplified copies of N-myc as shown by in situ hybridization with the N-myc probe pNb-1. One of the 7p HSRs was acquired during culture of CHP 134 cells, whereas the 2q HSR of CHP-382/JK was lost. Such findings highlight the continued process of N-myc amplification and transposition in vitro. To our knowledge, amplification of N-myc in multiple HSRs has not been documented previously in neuroblastoma cell lines. PMID- 2582422 TI - Restricted homology between human alpha 1 type IV and other procollagen chains. AB - Screening of a human fibroblast cDNA library with a mouse type IV procollagen clone resulted in one 1.05-kilobase isolate that was used to identify a 1.7 kilobase clone overlapping the former by less than 150 nucleotides. EcoRII digestion revealed that the larger clone exhibited the pattern characteristic of DNA coding for a collagenous sequence. Blot hybridization to RNA from mouse F9 stem cells and from these cells treated with retinoic acid and N6, O2'-dibutyryl cAMP showed induction of type IV mRNA. DNA sequencing and comparison of the derived amino acids with the reported protein data demonstrated that the clones encode part of the alpha 1 chain of human type IV procollagen. Alignment of alpha 1 (IV) with other human procollagens showed minimal but detectable homology. A small cluster of charged residues in the alpha chain is partially shared by type IV. In close proximity is an interruption in the alpha 1 (IV) Gly-Xaa-Yaa region corresponding to the 3' end of a unique proline-free, and therefore also less rigid, area in other collagen triple helices. Analysis of the carboxyl-terminal alpha 1 (IV) peptide showed a repeat symmetry possibly dictated by the six cysteines in each half of the structure. The position of five cysteines in addition to four tyrosine/tryptophan groups allowed a correlation to be drawn between the 3' noncollagenous type IV region and the larger, highly conserved carboxyl propeptides of other human procollagens. Such similarities in the different chains may define functional domains conserved throughout evolution. PMID- 2582424 TI - Molecular characterization of MT3 antigens by two-dimensional gel electrophoresis, NH2-terminal amino acid sequence analysis, and southern blot analysis. AB - The monoclonal antibody 109d6, which recognizes major histocompatibility antigen MT3-like serologic determinants, has been used to characterize the molecules bearing this determinant in HLA-DR4 and -DR7 homozygous cell lines by two dimensional gel and sequencing analyses. By these two criteria, these molecules are identical to each other. Southern blot analysis of genomic DNA from HLA-DR1 through -DR7 homozygous cell lines with DR beta-chain gene probes reveals a striking similarity in the pattern of hybridizing fragments between DR4 and DR7 haplotypes and among DR3, DR5, and DRw6 haplotypes reminiscent of the MT3/MT2 allodeterminant distribution. The sharing of the MT2 determinant between DR3, DR5, and DRw6 haplotypes and of the MT3 determinant between DR4 and DR7 haplotypes is part of a broader "homology," which may be a consequence of more recent separation of the haplotypes sharing the MT2 determinant on the one hand and the haplotypes sharing the MT3 determinant on the other hand. PMID- 2582425 TI - Cross-reactive idiotypes and common antigen binding specificities expressed by a series of murine B-cell lymphomas: etiological implications. AB - A series of 27 B-cell lymphomas (designated the CH series), induced in B10.H-2aH 4b p/Wts mice by intense adoptive immunization with sheep erythrocytes, was found to represent a subset of the total B-cell repertoire. This subset was characterized by expression of a limited number of Ig heavy chain variable regions, as evidenced by the presence of cross-reactive idiotypes and common antigen binding specificities. Twenty-one of the 27 CH lymphomas studied were classified into five groups, defined by a particular cross-reactive idiotype; four of these groups were linked in a single network. Seven of 16 idiotypes defined by absorption analysis were present on lymphomas bearing either kappa or lambda light chains and so were localized to the heavy chain variable region. The surface Ig on 14 CH lymphomas was found to be specific for epitopes on certain erythrocytes (bromelain-treated autologous erythrocytes, sheep, and chicken erythrocytes) or E. coli. We propose that the CH lymphomas represent the malignant counterparts of a subset of idiotypically related, normal B cells in B10.H-2aH-4b p/Wts mice. Perturbation of this idiotype network, by hyperimmunization with an antigen for which some of the members are specific (sheep erythrocytes), increases the risk for neoplasia. Possible mechanisms for this are discussed. PMID- 2582426 TI - Specific 5' and 3' regions of the mu-chain gene are undermethylated at distinct stages of B-cell differentiation. AB - The mu-chain gene is expressed differently in successive stages of B-lymphocyte development. The heavy chain product appears as a cytoplasmic constituent in pre B-cells, as part of the IgM receptor in maturing B cells, and as a component in the pentamer IgM antibody synthesized and secreted by the antigen-stimulated cell. We have used the methylation of CpG sequences as an assay system to define the chromatin changes associated with different expression of the mu-chain. The methylation status of eight index sites was followed by restriction enzyme analysis of murine cell lines representing the major stages in the developmental pathway. The analyses showed that a single Msp I/Hpa II site 5' to the immunoglobulin enhancer becomes undermethylated with the onset of mu-chain gene transcription. Four midgene Msp I/Hpa II sites exhibit a progressive loss of methyl groups unrelated to changes in mu-chain gene expression, whereas a Msp I/Hpa II site and two Hha I sites surrounding the exon encoding the carboxyl terminus of the secreted form of mu chain (mus) become undermethylated during the transition to IgM secretion. These results indicate that structural changes in local regions of the mu-chain gene correlate with specific developmental events. PMID- 2582427 TI - Isolation and characterization of mouse Thy-1 genomic clones. AB - The mouse Thy-1.2 gene was isolated from a C57Bl/6 cosmid library and its nucleotide sequence was determined from an 8-kilobase-long EcoRI fragment. The predicted amino acid sequence indicates that the mouse Thy-1 molecule contains a 19 amino acid leader peptide and the 112 amino acids reported previously from protein sequence analysis, plus 31 extra amino acids at the carboxyl terminus. These 31 amino acids contain a stretch of 20 amino acids, at positions 124-143, which is highly hydrophobic. RNA transfer blot analysis of RNA from mouse tissues indicates that the sequence coding for these 31 amino acids is present on poly(A) containing RNA of brain and thymus tissues. This hydrophobic segment very likely provides the basis for integration of Thy-1 within the plasma membrane. The entire coding sequence of Thy-1 is distributed among three exons, encoding amino acid residues -19 to 8, -7 to 106, and 107 to 143, respectively. Comparison of the mouse and rat Thy-1 genes shows that both have a similar gene organization and encode a highly conserved transmembrane segment. PMID- 2582429 TI - Insulin-related genes expressed in human placenta from normal and diabetic pregnancies. AB - Rapid growth of human fetal tissues requires insulin or insulin-like growth factors. A high rate of human fetal growth occurs between implantation and about 14 weeks of gestation. Fetal pancreatic insulin secretion begins much later. Since maternal insulin does not cross the blood/placental barrier, other sources of insulin or insulin-like growth factors may be provided for fetal development. We report here that placental polyadenylylated RNAs from the first and third trimester of normal pregnancy as well as from term pregnancies of diabetic mothers hybridize to a 32P-labeled cloned cDNA of an insulin-related sequence expressed in fetal pancreas. Moreover, placentas from diabetic women express much more of these sequences. These results suggest that insulin-related genes are expressed in placental tissue during fetal development and may be a source of growth-promoting hormones for the human fetus. Fetuses developing in diabetic women receive a large influx of glucose. This in turn may stimulate the expression of insulin-related sequences, which may result in higher utilization of glucose, thus bringing about the macrosomia and high incidence of malformation and still-births known to result from pregnancies in diabetics. PMID- 2582428 TI - Inhibition of platelet aggregation by a monoclonal antibody against human fibronectin. AB - A monoclonal antibody (A3.3) has been generated against human platelet fibronectin (FN). A3.3 reacts with human plasma FN but with no other plasma proteins. A3.3 was found to inhibit thrombin- or ionophore A23187-stimulated aggregation of gel-filtered platelets in a concentration-dependent manner in both an aggregometer assay and a sensitive well plate aggregation assay. The antibody does not block secretion of serotonin. Four other anti-FN monoclonal antibodies that recognize different epitopes on FN than A3.3 does have no effect on platelet aggregation. A3.3 does not block the adhesion of CHO cells to FN-coated surfaces, indicating that it does not bind to the identified cell-binding domain of FN. A3.3 reacts with a 160/140-kDa doublet, known to contain the cell-binding domain, that is produced by digestion of FN with elastase or thermolysin. However, the antibody does not react with lower molecular weight species that also contain the cell-binding domain or with any of the other identified domains of FN. The A3.3 epitope is extremely protease sensitive and the smallest fragment found in any digest that retains reactivity with A3.3 is a 70-kDa peptide produced in low yield by mild thermolytic cleavage of FN. These data suggest that A3.3 defines a functional site present on both the platelet and plasma FN molecule that has a direct role in platelet aggregation. PMID- 2582431 TI - Decrease in polylactosaminoglycans associated with lysosomal membrane glycoproteins during differentiation of CaCo-2 human colonic adenocarcinoma cells. AB - The proportion of labeled polylactosaminoglycans found in glycoproteins decreases during spontaneous differentiation of CaCo-2 human colonic adenocarcinoma cells to enterocytes in culture (A. Youakim and A. Herscovics, Biochem. J., 247: 299 306, 1987). To identify polylactosaminoglycan-containing glycoproteins, CaCo-2 cells were incubated with [3H]glucosamine or [3H]fucose, for 24 h, and membrane glycoproteins solubilized with 0.5% Nonidet P-40 were fractionated by affinity chromatography on Datura stramonium (DSA)-agarose. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography showed that a restricted set of glycoproteins with a molecular weight of about 100,000 bound to DSA-agarose. These labeled glycoproteins were shown to contain polylactosaminoglycans by DSA agarose chromatography and endo-beta-galactosidase digestion of Pronase-derived glycopeptides. Immunoprecipitation of the [3H]glucosamine-labeled Nonidet P-40 extract with polyclonal antibodies to the lysosomal membrane proteins h-lamp-1 and h-lamp-2 followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography also revealed a band with a molecular weight of about 100,000. The immunoprecipitates were digested with Pronase, and the resulting glycopeptides were first fractionated on Bio-Gel P-6 into excluded (Fraction I) and included (Fraction II) glycopeptides, and then by DSA-agarose affinity chromatography. A much greater proportion of labeled glycopeptides in undifferentiated cells (3 to 5 days in culture) than in differentiated cells (19 to 27 days in culture) was recovered in Fraction I; these glycopeptides were bound to DSA-agarose and were sensitive to endo-beta-galactosidase. This decrease in polylactosaminoglycans was associated primarily with h-lamp-1. These results indicate that h-lamp-1 of CaCo-2 cells contains polylactosaminoglycans and that it undergoes a change in glycosylation with differentiation. PMID- 2582430 TI - Flow cytometric determination of the frequency and heterogeneity of expression of human melanoma-associated antigens. AB - We used flow cytometry to measure the expression of human melanoma antigens on cell suspensions dissociated from metastatic masses. The objective was to study the heterogeneity between tumor samples from different patients and between different tumors excised from a single patient. Fifty-three metastases excised from 34 melanoma patients were analyzed with a panel of nine murine monoclonal antibodies (MOABs). Melanoma cells were stained by an indirect fluorescent method and analyzed on a Coulter EPICS C flow cytometer after gating to exclude tumor infiltrating leukocytes and dead cells. The most consistently and most strongly expressed antigen was the high-molecular-weight proteoglycan (detected by the MOAB 9.2.27), which was expressed on 95% of the melanoma specimens and by a high proportion of cells within each specimen (mean +/- SE, 79.2 +/- 5.5). However, strong expression of this antigen was limited to melanoma cells that had been dissociated mechanically and was markedly diminished by exposure to collagenase. Culture of collagenase-dissociated tumor cells for 24 to 48 h resulted in reexpression of the antigen. The expression of other melanoma-associated antigens was not affected by collagenase treatment, but for these antigens there was more variability between cells from an individual tumor and between tumors from different patients. The percentage of enzyme-dissociated tumors considered positive for MOAB binding (defined as at least 10% of cells positive) and the mean +/- SE of the percentage of positive cells within a tumor were as follows: MOAB ME-9-61 (antigen, p97) = 84% + (41.2 +/- 5.4%); MOAB ME-20.4 (antigen, nerve growth factor receptor) = 40% + (18.7 +/- 5.1%); MOAB ME-24 (antigen, ganglioside GD3) = 84% + (50.8 +/- 4.8%); MOAB ME-311 (antigen, ganglioside 9-O-acetyl-GD3) = 76% + (42.5 +/- 5.1%); MOAB ME-361 (antigen, mainly ganglioside GD2) = 3% + (1.9 +/- 0.8%); MOAB 3F8 (antigen, ganglioside GD2) = 36% (10.5 +/- 3.8%); MOAB 14G2a (antigen, ganglioside GD2) = 86% + (46.0 +/- 6.7%); MOAB L243 (antigen, HLA-DR) = 56% + (22.5 +/- 5.5%). In 19 cases, we were able to compare the antigenic profiles of two tumors excised from the same patient at different times. Analysis by nonindependent t test showed no significant differences in MOAB binding between the paired tumors. Moreover, linear regression analysis indicated that there was a linear relationship, with a slope approximately = 1, between the percentage of positive cells in Tumor 1 versus Tumor 2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2582432 TI - Reversal by cefoperazone of resistance to etoposide, doxorubicin, and vinblastine in multidrug resistant human sarcoma cells. AB - The cephalosporins are a family of semisynthetic antibiotics, some of which have structural features associated with substrates for the multidrug transporter, P glycoprotein. The activity of a series of six cephalosporins in reversing multidrug resistance (MDR) was examined in MDR variants (Dx5 cells) of the human sarcoma line MES-SA. Dx5 cells express high levels of the mdr1 gene product P glycoprotein and are 25- to 30-fold resistant to doxorubicin (DOX), etoposide (VP 16), and vinblastine (VBL). Cytotoxicity was measured by the MTT assay. Cefoperazone (1.0 mM) was the most effective modulator of MDR, lowering the IC50 for VP-16 by 29-fold (29x), for VBL by 16x, and for DOX by 14x. Ceftriaxone at 1.0 mM produced 10x modulation of VP-16 cytotoxicity, 8x for DOX, and 2x for VBL. The reversal of resistance was concentration dependent, decreasing to 4x and 5x, respectively, for DOX with 0.25 mM cefoperazone and ceftriaxone. No modulation of cytotoxicity was observed in the parental MES-SA cells, which do not express mdr1. Cefazolin, cefotetan, cephradine, and ceftazidime were ineffective, producing less than 5x modulation of DOX at 1.0 mM. Among these cephalosporins, cefoperazone and ceftriaxone were the most highly protein bound in the media (30 and 52%), and the most lipid soluble, with octanol/water partitioning coefficients of -0.49 and -0.60. Varying the serum concentration in medium from 5 to 50% had less than a two-fold effect on the modulation of MDR by ceftriaxone. The ability to reverse MDR among these agents is associated with lipid solubility, high protein binding, a polycyclic planar geometry, and the presence of the piperazine group in cefoperazone. These data and the potential for achieving high tissue concentrations indicate that cefoperazone merits further study as a modulator of MDR. PMID- 2582433 TI - Metastatic potential of human colorectal carcinomas implanted into nude mice: prediction of clinical outcome in patients operated upon for cure. AB - To determine whether the production of experimental hepatic metastases in athymic nude mice by human colorectal carcinomas (HCC) correlated with the clinical outcome in patients, we harvested colorectal carcinomas from 82 patients, dissociated the tumors with collagenase and DNase, and injected them into groups of nude mice, either in the flank to assess experimental tumorigenicity or into the spleen to produce experimental metastasis in the liver. Growth in mice was then associated with clinicopathological factors and clinical outcome. Growth of HCC in either the flanks or the livers of nude mice was associated with the time to recurrence in a Wilcoxon analysis. Analysis of the outcome data in a Cox proportional hazards model suggested that there was an interaction between tumorigenicity and metastatic potential of HCC in nude mice and serum CEA concentration in the patient and stage of disease. A univariate analysis indicated that both tumorigenicity and metastatic potential of HCC in nude mice were significantly associated with the serum CEA concentration of the patient but not with the other variables of stage of disease, mucin production, local tissue invasion, state of differentiation, or sex. A subset of 57 patients was operated upon for cure and followed prospectively for up to 61 months. Tumorigenicity and, to a lesser extent, experimental metastatic potential were associated with disease recurrence in 23 of these patients. Seventy-eight % of the subset of patients who were operated upon for cure developed liver metastasis as one site of their progressive disease. Thus, the ability of HCC cells isolated from surgical specimens to grow in athymic nude mice correlates with the development of advanced disease in patients. PMID- 2582434 TI - Establishment of a melphalan-resistant rhabdomyosarcoma xenograft with cross resistance to vincristine and enhanced sensitivity following buthionine sulfoximine-mediated glutathione depletion. AB - A melphalan-resistant human rhabdomyosarcoma xenograft, TE-671 MR, was established in athymic mice by serial melphalan treatment of the parent xenograft, TE-671, at the 10% lethal dosage (LD10); significant resistance was evident after ten passages of the tumor. TE-671 MR demonstrated a doubling time of 3.5 days and a latency period to 1000-mm3 tumors of 27.5 days. The glutathione level of TE-671 MR was 2.36 mumol/g tumor, wet weight, 2-fold higher than the parent line. The glutathione S-transferase activity of TE-671 MR was 117.8 mumol/min/mg protein, essentially unchanged from the parent line. Although TE-671 MR demonstrated cross-resistance to vincristine, dot blot analysis did not reveal an elevated expression of mdr1 mRNA in the resistant line. TE-671 MR demonstrated a 9.7-day growth delay following treatment with melphalan at the LD10 (compared to 20.9 days for the parent line). Treatment with L-buthionine-SR-sulfoximine (BSO) resulted in increased sensitivity to melphalan subsequently administered at 50% of the LD10 (melphalan alone, growth delays of 3.7 and 4.6 days in duplicate trials; melphalan plus BSO, growth delays of 7.2 and 9.8 days). Sensitivity to melphalan equal to that of the parent line TE-671 was not achieved, however. Treatment with BSO did not result in significantly enhanced sensitivity to subsequently administered vincristine (50% of the LD10) (vincristine alone, growth delays of 6.8 and 6.9 days in duplicate trials; vincristine plus BSO, growth delays of 10.9 and 7.5 days). These results suggest that generation of melphalan resistance may be associated with development of cross-resistance to vincristine; this resistance may be associated with (although not necessarily mediated by) glutathione elevation; this resistance may be partially overcome by BSO-mediated depletion of glutathione. PMID- 2582435 TI - ICI 164,384, a pure antagonist of estrogen-stimulated MCF-7 cell proliferation and invasiveness. AB - Estrogen is known to stimulate the proliferation and basement membrane invasiveness of the MCF-7 human breast cancer cell line. We have compared the new steroidal antiestrogen ICI 164,384, the triphenylethylene 4-hydroxytamoxifen (OHT), and the benzothiophene LY 117018, for their effects on the proliferation and invasiveness of the MCF-7 cell line and its antiestrogen-resistant variant LY 2. While all three antiestrogens blocked the proliferative effects of 17 beta estradiol on MCF-7 cells, OHT and LY 117018, but not ICI 164,384 stimulated their proliferation in the absence of estrogen. The proliferative effects of OHT and LY 117018 were blocked by ICI 164,384. Basement membrane invasiveness of MCF-7 cells was stimulated by 17 beta-estradiol and OHT, but not LY 117018 or ICI 164,384. Both ICI 164,384 and LY 117018 were able to block the invasiveness induced by either 17 beta-estradiol or OHT. The LY-2 antiestrogen-resistant variant of the MCF-7 cell line showed increased basal proliferation, and responded only slightly to estrogen. ICI 164,384, but not OHT or LY 117018 antagonized the effects of 17 beta-estradiol, but did not reduce proliferation below control levels. The LY-2 line was not resistant to the antiestrogenic effects of LY 117018 or ICI 164,384 on invasiveness, and was stimulated by LY 117018 for this parameter. Thus, ICI 164,384 is a pure antiestrogen for MCF-7 cell proliferation and invasiveness, and may offer clinical advantage over nonsteroidal antiestrogens which can stimulate these activities in tumor models in vitro. PMID- 2582436 TI - Reduction in cis-diamminedichloroplatinum(II)-induced cytotoxicity, sister chromatid exchange, and DNA interstrand cross-links in 9L cells treated with the polyamine biosynthesis inhibitor (2R,5R)-6-heptyne-2,5-diamine. AB - The effects of depletion of intracellular levels of the polyamines putrescine and spermidine on cis-diamminedichloroplatinum(II)-induced cytotoxicity, sister chromatid exchanges, DNA interstrand cross-linking, and intracellular glutathione levels were studied in 9L rat brain tumor cells pretreated with the ornithine decarboxylase inhibitor (2R,5R)-6-heptyne-2,5-diamine (R,R-MAP). Pretreatment of 9L cells with R,R-MAP for 48 h decreased cis-diamminedichloroplatinum(II) cytotoxicity with an average dose reduction ratio of 0.55 at both the 5 and 10% survival levels; addition of putrescine partially prevented this effect. The number of sister chromatid exchanges and DNA interstrand cross-links was also reduced (31 and 38%, respectively). Within 24 h of treatment with R,R-MAP, intracellular glutathione levels began to increase relative to untreated control cells and were significantly elevated in R,R-MAP-treated cells 48-72 h after addition of drug. We discuss several mechanisms by which polyamine depletion could reduce cis-diamminedichloroplatinum(II) toxicity. PMID- 2582437 TI - Changes in calcitonin gene RNA processing during growth of a human medullary thyroid carcinoma cell line. AB - The ratios of calcitonin (CT) to calcitonin gene-related peptide (CGRP) mRNA, both generated by alternative RNA processing from the same primary RNA transcript, are shown by Northern blotting of cytoplasmic RNA to vary as a function of growth in a human medullary thyroid carcinoma cell line (TT). Upon initial seeding, CT mRNA levels are relatively high, and CGRP mRNA levels are relatively low. During the early logarithmic growth phase, CGRP mRNA levels rise severalfold, while CT mRNA levels change only slightly. As the cells approach confluence, both CT and CGRP mRNA levels rise. Subsequently, CGRP mRNA levels fall substantially in postconfluent cells, while CT mRNA levels remain high. By actinomycin D blocking of nascent transcription, we have shown that these growth related, reversible changes in the ratio of CT to CGRP mRNA are not due to changes in mRNA stability. Our data rather suggest that TT cells reversibly alter alternative RNA-processing patterns dependent upon growth conditions in vitro, such that CT mRNA is lowest and CGRP mRNA is highest during rapid growth. The mechanisms underlying this RNA-processing alteration may play a role in certain patients with aggressive forms of medullary thyroid carcinoma, in whom a decrease or loss of CT levels heralds a poor prognosis. PMID- 2582438 TI - Frequent alteration of the DF3 tumor-associated antigen gene in primary human breast carcinomas. AB - The gene for the human DF3 breast carcinoma-associated antigen contains a conserved (G + C)-rich 60-base pair tandem repeat and maps to chromosome 1q21-24. In the present study we isolated and characterized 1220 base pairs of nonrepetitive adjacent sequences. Multiple alleles were identified by fragment size. Signal intensity of hybrids with the tandem and unique sequence probes indicated that allelic variation is due to different numbers of repeats. Probes for both the tandem and the unique sequences were used to study the DF3 locus in human breast tumor DNAs. Seventy of 110 breast tumor DNAs were informative at the DF3 locus. Of these, 20 (29%) showed a loss of heterozygosity, while eight (11%) had an increased copy number of one allele. In some cases, the loss of heterozygosity or increased copy number did not extend to other markers on chromosome 1q or 1p. These data indicate that the chromosomal region around the DF3 locus is affected by mutations at high frequency. PMID- 2582439 TI - Expression of transforming growth factor alpha in normal human adult kidney and enhanced expression of transforming growth factors alpha and beta 1 in renal cell carcinoma. AB - Normal kidney and renal cell carcinoma tissues from ten patients were studied for mRNA and DNA for both transforming growth factors alpha and beta 1. Northern and Southern hybridizations were conducted on samples extracted from the solid tumor and surrounding normal tissues and two tumor-derived cell lines. Low levels of constitutive expression of TGF-alpha mRNA were detected in all normal kidney tissues; six of the ten patients, however, demonstrated an increased (2- to 8 fold) expression of TGF-alpha in the tumor versus normal kidney as determined by densitometry of RNA blots. All ten patients had elevated mRNA levels for TGF-beta 1 in the tumor (2.5-to 22-fold increase) relative to normal kidney. Two tumor derived cell lines also expressed TGF-alpha and TGF-beta 1 mRNA. Southern blot hybridization of the DNA extracted from the normal tumor pairs revealed no gene amplification or gross rearrangement for either the TGF-alpha or TGF-beta 1 genes. These results demonstrate the expected constitutive expression of TGF-beta 1 by normal kidney; however, the constitutive expression of TGF-alpha by Northern blot analysis in normal adult human kidney is previously unreported. Enhanced expression of TGF-alpha and TGF-beta 1 mRNA in solid tumor may be related to the development of renal cell carcinoma. PMID- 2582440 TI - Dose response of hepatocyte replication in rats following continuous exposure to diethylnitrosamine. AB - Chronic exposure to the hepatocellular carcinogen diethylnitrosamine (DEN) causes a dose-dependent accumulation of the promutagenic DNA adduct O4 ethyldeoxythymidine in hepatocytes and increases in the number of initiated hepatocytes as indicated by gamma-glutamyl transpeptidase positive foci. Initiation is thought to be dependent on the quantity of promutagenic DNA adducts, their efficiency for causing base pair mismatch, and the extent of replication in the target tissue. If the extent of replication is also dose dependent, then this dependence could alter the number of promutagenic DNA adducts that mispair prior to repair and enhance the clonal expansion of initiated cells. We have examined the effect of DEN on hepatocellular proliferation over a wide range of doses. Six-week-old male F-344 rats were exposed to drinking water containing 0.4, 1, 4, 10, 40, or 100 ppm DEN for 1, 4, or 10 weeks. Following exposures to DEN, rats were injected i.p. with [3H]thymidine, sections from the left, right median and anterior right lobes of the liver were processed for autoradiography and the labeling index of hepatocytes determined. A progressive increase in hepatocyte replication was induced by exposure to 40 and 100 ppm DEN. This was especially marked in the left lobe where 40 and 100 ppm DEN induced increases of 800 and 1500%, respectively, over controls after 10 weeks of exposure. Exposure to 4 and 10 ppm DEN resulted in a 300 to 400% increase in hepatocyte replication in all lobes, whereas 1 and 0.4 ppm DEN did not significantly increase cell proliferation compared to unexposed controls. PMID- 2582442 TI - Expression and precursor processing of neuropeptide Y in human pheochromocytoma and neuroblastoma tumors. AB - The expression of the potent vasoactive peptide neuropeptide Y (NPY) was studied in 16 clinically and/or histologically diagnosed human pheochromocytomas and 3 human neuroblastoma tumors. All tumors contained NPY in concentrations ranging from 21 pmol/g of tissue, similar to that found in normal adrenal tissue, to 91,000 pmol/g (median, 1,700 pmol/g). Three control tumors of Cushing's type did not contain NPY. An almost total proteolytic processing of pro-NPY to normal NPY was observed in the tumors (median, 93%; range, 72-100%). A positive correlation between the processing efficiency and the NPY content was also observed. The small amount of pro-NPY found in the tumors was characterized by "in vitro conversion" with endoproteinase Lys-C. In the tumor extracts, the majority of the NPY immunoreactivity, corresponding in size to the NPY standard, also behaved like synthetic NPY by high performance liquid chromatography and isoelectric focusing. As assessed by both its elution position in isoelectric focusing and its reaction with an antiserum specific for the COOH-terminal amidated sequence, the peptide produced by the tumors was found to be efficiently amidated, a modification which is essential for the biological activity of NPY. It is concluded that although only a subset of chromaffin cells express NPY, a very high number of pheochromocytomas and neuroblastomas produce correctly amidated and thus biologically active NPY in large amounts, and that this is of potential importance for tumor-related cardiovascular symptoms and for autocrine stimulation of tumor cells. PMID- 2582441 TI - Constitutive expression and abnormal glycosylation of transferrin receptor in acute T-cell leukemia. AB - The expression of transferrin receptors (TrfRs) was investigated in acute T-cell leukemia (T-ALL) blasts at the molecular, biochemical, immunological, and functional level. TrfRs, although not detected on quiescent T-cells from normal adults, are constitutively expressed at high level on the blasts from all T-ALL patients and bind normally to transferrin. Their number is modulated by the intracellular iron level, but is independent of exogenous interleukin 2. They also exhibit immunological and biochemical abnormalities, in that: (a) they react preferentially with monoclonal antibodies (MAb) that recognize ligand-binding domains of TrfR (42/6 and 43/31), as compared to MAbs (B3/25, OKT9) that interact with the nonligand binding domains; (b) they have a reduced molecular weight, as compared to TrfR on normal thymocytes and activated T-lymphocytes: this phenomenon is apparently related to a defective glycosylation. It is noteworthy that expression of TrfR was not observed in a large series of other types of acute leukemias, i.e., pre-B, B, and myeloid leukemias, excluding erythroleukemias. The constitutive, high level expression of TrfRs on T-ALL blasts may play a key role in the stepwise progression of this malignancy and particularly provide a proliferative advantage to T-ALL blasts as compared to normal T-lymphocytes. Furthermore, indirect evidence suggests that the glycosylation defect of TrfR on T-ALL blasts contributes to their tumorigenic capacity. PMID- 2582443 TI - Expression and precursor processing of neuropeptide Y in human and murine neuroblastoma and pheochromocytoma cell lines. AB - The synthesis and processing of the precursor for neuropeptide Y (NPY) were studied in 16 human and murine neuroendocrine cell lines. Eight of the cell lines, NS-20Y, PC12, LA-N-5, CHP-234, SMS-KCNR, SH-SY5Y, SMS-KCN, and BE(2)-M17, produced sufficient quantities to permit chromatographic characterization of the NPY immunoreactivity. Although the cell lines varied in the amount of NPY they produced, both within and between cell lines, they displayed a relatively constant pattern of posttranslational modifications. In contrast to observations in tumor extracts (M. M. T. O'Hare and T. W. Schwartz, Cancer Res., 49: 7010 7014, 1989), all cell lines studied contained a substantial amount of the intracellular NPY in the form of the unprocessed propeptide, 57% (range, 33-72%) as characterized by both gel filtrations (32 experiments in 8 cell lines) and "in vitro conversion" with endoproteinase Lys-C. In the majority, 4 of 6 cell lines studied, almost all of the NPY, which by size corresponded to the mature 36-amino acid form, was amidated as assessed by isoelectric focusing and by a radioimmunoassay specific for the COOH-terminal amide group of the peptide. Both the propeptide and smaller molecular forms of NPY were secreted from the cell cultures; however, proteolytic degradation in the tissue culture medium prevented a detailed, meaningful characterization of these peptides. It is concluded that many neuroendocrine cell lines, especially those derived from human neuroblastomas, express the NPY gene; the cells display a partly impaired dibasic processing capacity but they generally amidate the products efficiently. PMID- 2582444 TI - Immunotherapy of mice with a large burden of disseminated lymphoma with low-dose interleukin 2. AB - Successful immunotherapy with recombinant interleukin 2 (rIL-2) of mice bearing a large burden of lymphokine-activated killer-resistant disseminated SL2 lymphoma is described. When mice were challenged i.p. with 2 x 10(4) SL2 cells on day 0 and treated with daily i.p. injections of 5,000 units rIL-2 on days 3-7, no therapeutic effect was observed. However after treatment with daily IL-2 injections on day 10-14, 25% of the mice survived. Ten days after this tumor challenge more than 10(8) SL2 cells were present growing as ascitic tumor. On day 10, SL2 cells were also present as solid tumor in the greater omentum and as metastases in lungs and liver. Surviving mice were able to reject a second challenge with SL2 cells given on day 60. A second challenge with P815, another DBA/2 tumor, resulted in death of the mice due to tumor development. This finding is of particular importance as the SL2 cells are resistant to lymphokine activated killer activity. Thus local (i.p.) injection of low dose rIL-2 can cause the systemic rejection of advanced and metastasized cancer. Our data indicate that IL-2 can strongly enhance a specific immune reaction against tumor cells. PMID- 2582445 TI - Increased therapeutic gain of combined cis-diamminedichloroplatinum (II) and whole body hyperthermia therapy by optimal heat/drug scheduling. AB - To maximize therapeutic gain, the timing sequence of whole body hyperthermia (WBH) and cis-diamminedichloroplatinum (II) (DDP) was examined. Normal tissue injury as well as growth of a s.c. transplanted fibrosarcoma were measured in F344 rats treated with variable schedules of WBH and DDP. Simultaneous application of DDP (2 mg/kg i.v.) with WBH (120 min at 41.5 degrees C) resulted in severe renal injury, body weight loss, and mortality; while sequential use of the modalities caused minimal to no toxicity. DDP or WBH alone produced only minimal tumor growth delay, whereas supraadditive antitumor effects occurred with all tested schedules of DDP combined with WBH, regardless of sequence or interval between the two modalities. We designated the ratio of antitumor effect to nephrotoxicity as specific therapeutic efficacy (STE). DDP given simultaneously with WBH produced the lowest STE (0.6-1.2), which was less than or equal to either DDP (STE = 1.2) or WBH (STE = 1.5) alone. On the other hand, schedules of DDP prior to and after WBH resulted in a STE of 1.8-3.0, a supraadditive effect. These results indicate that an optimal scheduling of DDP with WBH significantly improves therapeutic gain by reducing normal tissue injury while maintaining enhanced antitumor activity. PMID- 2582446 TI - Characterization of IgG and IgM antibodies induced in melanoma patients by immunization with purified GM2 ganglioside. AB - The ganglioside GM2 is a differentiation antigen expressed on the cell surface of human malignant melanomas and other cancers of neuroectodermal origin. We have previously reported that immunization with purified GM2 combined with Bacillus Calmette-Guerin as adjuvant and pretreatment with low-dose cyclophosphamide induced production of antibodies against GM2 in five of six patients. We have now extended our study and analyzed the induced antibodies against GM2 were not detected. After immunization, high-titer IgM antibodies were induced in 17 of 24 patients, and high-titer IgG antibodies in eight cases. Additional treatment of 12 patients with cimetidine, a histamine H2 receptor antagonist reported to have antisuppressor cell activity, had no effect on GM2 antibody titers. Antibodies against asialo-GM2 were present in all patients, and antibodies against GM1 were present in 33% of patients, before and after immunization. Antibodies induced by immunization were specific for GM2, though some reacted predominantly with N acetylneuraminic acid GM2 (GM2), and some reacted with GM2 and N glycolylneuraminic acid GM2(NeuGcGM2). The pattern of reactivity with GM2 is consistent with the response to T-cell-independent antigens: both IgM and IgG antibody responses against GM2 were short lived; peak titers seen after initial and secondary vaccinations were similar; and delayed-type hypersensitivity responses to skin test challenges with GM2 were not detected in any patients. However, the IgG response typed as predominantly IgG1 and IgG3, not IgG2 as might be expected for carbohydrate antigens (which are generally T-cell-independent antigens). Because IgG1 and IgG3 antibody responses are usually to T-cell dependent antigens, the humoral immune response elicited by GM2 vaccination has both T-cell-dependent and T-cell-independent characteristics. These IgM and IgG responses against this neuroectodermal differentiation antigen expressed on melanoma cells have been induced without evidence of neurological or other toxicity. PMID- 2582448 TI - Characterization of two cell lines with distinct phenotypes and genotypes established from a patient with renal cell carcinoma. AB - Two human renal carcinoma cell lines have been established from the same patient. One cell line (CCF-RC1) was obtained from the primary tumor and the second (CCF RC2) was established from cells of the renal vein effluent of the perfused tumorous kidney. Although they were established from the same patient, the cell lines differed in certain biological properties. They have been passaged up to 50 times in vitro for about two years. Each has an epithelial morphology and exhibits mutilayering. Cell cycle time of CCF-RC1 and CCF-RC2 was 34 and 36 h, respectively. They exhibited anchorage independent growth, and the plating efficiency of CCF-RC2 in soft agar was higher than that of CCF-RC1. Both lines induced tumors in nude mice at the site of s.c. injection closely resembling the original tumor in histological examination. Electron microscopic features of both tumors in nude mice were consistent with epithelial origin. Doubling time of CCF RC1 and CCF-RC2 in nude mice was 11 and 12 days, respectively. CCF-RC1 and CCF RC2 have hypotetraploid karyotype and modal numbers of 83 and 73, presenting two and three marker chromosomes, respectively. Immunocytology with commercial monoclonal antibodies against renal carcinoma (URO-3) and cytokeratin (Mac 6) showed positive reactions with both lines, suggesting that these cell lines derived from renal epithelium. A murine monoclonal antibody (2E11) was generated against CCF-RC2 by the hybridoma technique; 2E11 reacted with CCF-RC2, but not with CCF-RC1. These cell lines may provide a useful model for the study of tumor heterogeneity and its relationship to metastasis. PMID- 2582447 TI - Glycosphingolipids in Bomirski transplantable melanomas in hamsters. AB - The glycosphingolipid compositions of Bomirski melanomas at different stages of differentiation, including Ab amelanotic melanoma (fast growing), Ma melanotic melanoma (slow growing), and MI hypomelanotic melanoma (slow growing), were studied. The total concentration of lipid-bound sialic acid in Ab amelanotic melanoma was found to be much lower than those in Ma and MI melanomas (0.8 micrograms versus 1.4 micrograms and 1.4 micrograms/mg of dry tissue, respectively). The ganglioside patterns in melanoma tissues were composed mainly of three components, which were confirmed as NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer (GM3), acetyl1-9-O-NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1 1'Cer (9-O-acetyl-GD3), and NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1 1'Cer(GD3) by structural analysis and monoclonal antibody detections. However, the relative ratios of these gangliosides expressed in the different types of melanomas were completely different. The MI melanoma tissues contained GM3 as the predominant species (greater than 90% of the total gangliosides) with very little of GD3 and 9-O-acetyl-GD3 gangliosides (less than 2% of the total gangliosides). In contrast, Ab amelanotic melanomas contained mainly 9-O-acetyl-GD3 (greater than 27%) and GD3 (greater than 51%) with lesser amounts of GM3. However, Ma melanoma had intermediate levels of GM3, GD3, and 9-O-acetyl GD3. The MI and Ma melanomas also contained monohexosylceramide (GL1) (about 60% as Gal beta 1-1'Cer and 40% as Glc beta 1-1'Cer in Ma and 30% as Gal beta 1-1'Cer and 70% as Glc beta 1-1'Cer in MI) and Gal beta 1-4Glc beta 1-1'Cer as the predominant neutral glycosphingolipid species. In contrast, Ab melanoma tissues contained more GalNAc beta 1-3GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1'Cer (Gb5), Gal alpha 1-4Gal beta 1-4Glc beta 1-1'Cer (Gb3), and GalNAc beta 1-3Gal alpha 1-4Gal beta 1 4Glc beta 1-1'Cer (Gb4) than MI and Ma melanomas. Our data suggest that the expression of glycosphingolipids in hamster melanoma cells may be closely related to cell growth and the degree of differentiation, with slow growing, highly differentiated cells expressing GM3 and GL1, and fast growing, undifferentiating cells having a preponderance of GD3, 9-O-acetyl-GD3, Gb5, Gb3, and Gb4. PMID- 2582449 TI - Platinum incorporation and differential effects of cis- and trans diamminedichloroplatinum(II) on the growth of mouse leukemia P388/D1. AB - The parallel effects of cis-diamminedichloroplatinum(II) (1 microM) or trans diamminedichloroplatinum(II) (20 microM) on the growth of mouse leukemia P388/D1 in culture, on the cellular content of protein/DNA, on the average cell volume, and on the distribution in different phases of the cell cycle were measured over a period of 70 h and compared with the amount of platinum residing in the cells. Despite different concentrations in the culture medium, similar amounts of cis- and trans-diamminedichloroplatinum(II) were incorporated. The platinum content of cells passed through an early concentration maximum in the millimolar range and decreased during prolonged times of incubation. Effects of cis diamminedichloroplatinum(II) were marked and irreversible whereas those of trans diamminedichloroplatinum(II) were small and transient. Proliferation was inhibited, while synthesis of protein and DNA continued almost unaffected. Cells were arrested in G2-phase of the cell cycle, and their volume increased correspondingly. The results suggested an inhibition of mitotic events, rather than of DNA replication, that caused cell arrest. PMID- 2582451 TI - Effect of tight junctional resistance on penetration of LLC-PK1 epithelial cell layers by metastatic B16-F10 melanoma cells. AB - The relationship between tight junctional resistance of a tissue and its penetration by metastatic cells was examined in vitro using LLC-PK1 cells, an epithelial cell line derived from pig kidney, and B16-F10 cells, a murine melanoma cell line metastatic in syngeneic C57BL/6 mice. When grown to confluence on 8.0-microns pore size polycarbonate filters, LLC-PK1 cells formed tight junctions between adjacent cells which offered an electrical resistance to a nondestructive 20-mu ampere alternating current passed across the cell layer. B16 F10 cells seeded on top of an LLC-PK1 epithelial layer with a measured transepithelial resistance of approximately 300 omega x cm2 were unable to penetrate the epithelial barrier. The tumor-promoter 12-O-tetradecanoylphorbol-13 acetate (TPA) lowered the electrical resistance of the epithelial layer by 80% and simultaneously opened the epithelial barrier to penetration by metastatic cells. PMID- 2582450 TI - Immunohistochemical correlates of response to recombinant interleukin-2-based immunotherapy in humans. AB - We have evaluated immunohistochemical characteristics of tumors and the infiltrating cells in patients treated with various immunotherapy regimens. Forty eight patients with advanced malignancies were treated with high dose i.v. recombinant interleukin-2 alone or in combination with cyclophosphamide, recombinant tumor necrosis factor, recombinant interferon-alpha, antimelanoma antibody 9.2.27, adoptively transferred tumor infiltrating lymphocytes, or lymphokine-activated killer cells. Thirty-four patients with metastatic melanoma and two patients with breast carcinoma underwent excision of one or more s.c. metastases either before, during, or after treatment. Twelve patients with metastatic renal cell carcinoma underwent pretreatment nephrectomy and these tumors were also studied. Tumor cells were evaluated for class I (HLA-A,B,C) and II (HLA-DR) antigen expression and the mononuclear infiltrate was characterized using an avidin-biotin immunoperoxidase technique. All melanomas were class I antigen positive. Fifty-three % of biopsied metastatic melanoma lesions, 58% of primary renal cell carcinomas, and neither of the two breast carcinomas expressed class II antigen prior to therapy. The pretreatment expression of class II antigens by a tumor was not predictive of a clinical response to recombinant interleukin 2-based therapy. After treatment, however, seven of seven biopsied regressing individual metastases intensely expressed DR antigen on over fifty percent of the cells while only three of ten nonresponding lesions did so. Regressing lesions were permeated with macrophages and both CD4 and CD8 T-cell subsets. There were no CD1 or NKH-1 positive infiltrating cells detected in any lesion. The response to recombinant interleukin 2-based immunotherapy is associated with T-cell as well as macrophage infiltration. DR antigen expression by tumor cells and T-cell infiltrate appear in individual lesions to be associated with this response. PMID- 2582452 TI - Altered queuine modification of transfer RNA involved in the in vitro transformation of Chinese hamster embryo cells. AB - Altered queuine modification of tRNA has been correlated to neoplastic transformation, but no direct cause and effect relationship has been defined. In the present study, a potential role for this alteration has been assigned. The tRNA in normal Chinese hamster embryo cells is significantly more queuine modified than the tRNA in their transformed Chinese hamster embryo counterparts, even though the specific activity of the queuine modification enzyme is much lower in Chinese hamster embryo cells than in transformed Chinese hamster embryo cells. Substrate availability appears to be responsible for the queuine hypomodification of tRNA in the transformed cells, since addition of excess exogenous queuine to the culture medium results in incorporation of queuine into the anti-codon of the undermodified tRNAs. Most importantly, the excess queuine inhibits anchorage-independent growth of transformed Chinese hamster embryo cells, thereby implicating queuine hypomodification of tRNA in the expression of this transformed phenotype. PMID- 2582453 TI - Multiple resistance mechanisms in Chinese hamster cells resistant to 9 hydroxyellipticine. AB - We have previously shown that Chinese hamster lung cells resistant to 9 hydroxyellipticine, DC-3F/9-OH-E, display multiple phenotypical alterations including cross-resistance to a variety of drugs as well as loss of tumorigenicity. We now analyze a DC-3F/9-OH-E subline that has been maintained for a prolonged period of time in drug-free medium in order to clarify the relationships between the various phenotypic traits. The absence of selection resulted in a partial recovery of the ability to form colonies in soft agar as well as of the tumorigenicity in nude mice. In contrast, no change was observed with respect to population-doubling time. Our results also show that the resistance to 9-hydroxyellipticine, which is associated with an altered topoisomerase II activity, is stable in the absence of drug for more than 1 year. In contrast, the cross-resistance to doxorubicin is partially reversible and the cross-resistance to vincristine is totally reversible in the absence of selection. The cross-resistance to vincristine and doxorubicin is accompanied by a decreased drug uptake. Northern blot analysis shows that the multidrug resistance-associated Mr 170,000-180,000 glycoprotein is overexpressed in the DC 3F/9-OH-E cells and that the overexpression is lost in the absence of selection. We conclude that (a) the DC-3F/9-OH-E cells exhibit multiple mechanisms of resistance which can be dissociated, (b) the tumorigenicity and the altered topoisomerase activity are independent biochemical events whereas the oncogenic potential appears to follow the expression of the multidrug resistance, and (c) the multidrug resistance phenotype may be induced by a drug which is not itself recognized by the multidrug resistance mechanism such as 9-hydroxyellipticine. PMID- 2582455 TI - Reproductive and menstrual factors and risk of colorectal cancer. AB - The relation between reproductive and menstrual factors and the risk of colorectal cancer was investigated in a case-control study conducted in Northern Italy on 279 women with colon cancer, 153 with rectal cancer and 386 controls admitted to hospital for a wide spectrum of acute, nonneoplastic, nondigestive disorders. Compared with nulliparous women, the relative risks (RR) of colon cancer were 1.1 for one and two births, 1.3 for three or four, and 1.1 for five or more. Corresponding values for rectal cancer were 0.9 for one, 1.1 for two, 1.4 for three or four, and 0.8 for five or more births. No significant association emerged with number of abortions, and no consistent pattern of trends for both colon and rectum cancer was observed in relation to age at first or last birth. Women whose menarche occurred at age 15 or over were at significantly lower risk of colon cancer (RR 0.5, 95% confidence interval = 0.3-0.9), and the point estimate was below unity, though nonsignificantly, for rectal cancer too (RR = 0.7). There was no relation between age at menopause, duration of menstrual cycles, and cancers of the colon and rectum. The present study produced no evidence that reproductive factors are related to colorectal cancer in this population. With this sample size, it was possible to exclude relative risks below 0.8 for colon and 0.7 for rectal cancer among multiparous women versus nulliparous ones. These findings are thus inconsistent with the epidemiological evidence on reproductive and menstrual factors and breast cancer in this and other populations, with the sole potential exception of the reduced risk of colorectal cancer among women whose menarche occurred at age 15 or over. PMID- 2582454 TI - Heterogeneous response to differentiation induction in different clonal subpopulations of a rat rhabdomyosarcoma cell line (BA-HAN-1). AB - Three clonal subpopulations (A, B, C) isolated from the same rhabdomyosarcoma of the rat were tested and compared for their susceptibility to differentiation induction using retinoic acid (RA), dimethylformamide (DMF), and N monomethylformamide (NMF). These subpopulations differ in that a block to spontaneous differentiation is imposed at different stages which are characteristic for each subpopulation. Whereas tumor cell proliferation was significantly inhibited (P less than 0.001) in all three subpopulations, the effects of RA, DMF, and NMF on tumor cell differentiation were strikingly heterogeneous. The response was most marked in subpopulation C, as evidenced by a significant increase in the number of terminally differentiated myotube-like giant cells (P less than 0.001) and in biochemical differentiation, as indicated by the creatine kinase activity (P less than 0.05). Between 5% (DMF and NMF) and 30% (RA) of the mononuclear cells in subpopulation C exhibited thick and thin myofilaments, which were never observed in the mononuclear cells of the control. In contrast, subpopulation A and B responded to RA, DMF, and NMF quite heterogeneously with an increase in biochemical differentiation, whereas terminally differentiated myotube-like giant cells were never observed. These results demonstrate that the therapeutic potential of differentiation induction in malignant tumors may be impaired by tumor heterogeneity. PMID- 2582456 TI - Improved measurement of androgen receptors in human breast cancer. AB - Molybdate-stabilized androgen receptors have been quantitated in cytosols derived from 1026 malignant breast tumors including all new cases of primary breast cancer reported in the western region of Norway during the 3-year period 1985 1987. A simple single point saturation assay using the synthetic labeled ligand methyltrienolone was evaluated for this purpose. This approach also allowed the simultaneous determination of estrogen and progesterone receptor from the same cytosol preparation. The cytosol content of albumin was also recorded in order to control for dilution by extracellular proteins. Androgen receptor was the sex hormone receptor most frequently found both in primary and secondary breast cancer. In primary tumors 84.9% (723 of 852) showed a cytosol concentration higher than 10 fmol/mg protein compared to 71.2 and 67.1% for estrogen and progesterone receptors, respectively. This incidence is about 2 times higher than previously reported for androgen receptors in the literature and may be due to the stabilizing effects of molybdate and a serine protease inhibitor on the recovery of active binding sites in cytosol. Cytosol concentration of androgen receptor is generally lower than that of the other sex hormone receptors; the average level was 65.5 fmol/mg cytosol protein compared to 86.8 and 84.7 for estrogen and progesterone receptors, respectively. Both incidence and cytosol concentrations were lower for all sex hormone receptors in soft tissue metastasis than in the primary tumor. This decrease is not likely to be due to differences in tumor cellularity since metastatic tumors appear to be more cellular as judged from a lower cytosol content of extracellular proteins (albumin). No significant differences were observed in any parameter investigated between different metastatic sites (skin, lymph nodes). Androgen receptor levels were strongly correlated to estrogen and progesterone receptor concentration in both primary and secondary cancers. Cytosol androgen receptor concentration increases with age. This increase is more significant in metastatic than in primary tumors. Evidently, tumor cellularity is a confounding factor in primary tumors since tumor cytosols from younger patients showed a higher content of extracellular proteins. Receptor levels in lymph node metastasis did not exhibit age dependence. This may suggest that locally produced factors rather than circulating levels of sex steroids modulate tumor receptor expression. In metastatic tissues androgen receptors are present with twice the frequency of progesterone receptors and one in four of these tumors express androgen receptor as their sole sex hormone receptor. This supports the view that some of the beneficial effects of high dose progestin treatment of advanced breast cancer are mediated through the androgen receptor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2582457 TI - First Annual Pezcoller Symposium. Drug resistance--mechanisms and reversal. PMID- 2582458 TI - Progestin action and progesterone receptors in breast cancer. PMID- 2582459 TI - Nursing, a new tomorrow? PMID- 2582460 TI - Surprised by tears. PMID- 2582462 TI - Isolation of monosialyated oligosaccharides from human milk and structural analysis of three new compounds. AB - The monosialyated oligosaccharide fraction from combined samples of human milk was fractionated by gel filtration, ion-exchange chromatography, and h.p.l.c. with triethylamine as an ion-pairing reagent. Among the twelve oligosaccharides isolated, three were new compounds for which the following structures were established on the basis of chemical analyses, f.a.b.-m.s., and n.m.r. spectroscopy. PMID- 2582461 TI - Preparative synthesis of C-(alpha-D-glucopyranosyl)-alkenes and -alkadienes: Diels-Alder reaction. AB - The reaction of 2,3,4,6-tetra-O-benzyl-1-O-(p-nitrobenzoyl)-alpha-D-glucopyranose with (E)-penta-2,4-dienyltrimethylsilane and boron trifluoride etherate in acetonitrile afforded stereoselectively (E)-5-(tetra-O-benzyl-alpha-D glucopyranosyl)-1,3-pentadiene in good yield. The readily available penta-O benzoyl-alpha-D-glucopyranose reacted with allyltrimethylsilane in the presence of boron trifluoride etherate in acetonitrile to give 3-(tetra-O-benzoyl-alpha-D glucopyranosyl)-1-propene and its beta anomer in yields of 60% and 2.3%, respectively. Diels-Alder cycloaddition of maleic anhydride to diene 1 afforded the adduct cis,cis-3-(tetra-O-benzyl-alpha-D-glucopyranosylmethyl)cyclohex -4-ene 1,2-dicarboxylic anhydride in high yield. PMID- 2582463 TI - The complete structure of the capsular polysaccharide from Streptococcus sanguis 34. AB - A complete structure for the capsular polysaccharide of Streptococcus sanguis 34, which is responsible for coaggregation of this bacterium with Actinomyces viscosus T14V, an important step in the formation of dental plaque, is proposed, based partly on the 1H-n.m.r. spectrum, which was assigned by 2-dimensional COSY, homonuclear Hartmann-Hahn spectroscopy, and nuclear Overhauser effects. A phosphoric diester linkage was identified from the 31P-n.m.r. spectrum, and the linkage was determined from long range 1H-31P correlation spectroscopy. The proposed structure is supported both by methylation analysis before and after dephosphorylation and by g.l.c.-m.s. of the phosphorylated monosaccharides as their trimethylsilyl derivatives, isolated by partial hydrolysis of the polysaccharide. The structure is composed of repeating linear hexasaccharide units joined by a phosphoric diester linkage, i.e., [----PO4(-)----6)-alpha-D GalpNAc-(1----3)-beta-L-Rhap-(1----4)-be ta -D-Glcp- (1----6)-beta-D-Galf-(1--- 6)-beta-D-GalpNAc-(1----3)-alpha-D-Galp -(1----]n. PMID- 2582464 TI - [Modern trends in gerontology]. AB - The paper discusses the main problems in gerontology, geriatrics and care of old persons. It stresses the importance of the geriatric discipline and a new conception of providing health care and social services to persons of high age. PMID- 2582465 TI - [The most frequent localization of cerebral ischemia attacks. III. Status lacunaris cerebri]. AB - The initial two parts of a 3-volume study on cerebral ictus concerned with analysis of macroangiopathic ischaemic defects are concluded with a final study analyzing microangiopathic defects. In a group of 93 patients with status lacunaris cerebri, the authors evaluated the presence and morphology of three main manifestations of status lacunaris: cerebral atrophy (periventricular and cortical), subcortical arteriosclerotic encephalopathy and the position of cerebral lacunae. The cerebral lacunae were mostly localized at the interphase of the individual cerebrovascular systems, which shows that their pathogenesis was due to interterritorial infarct. PMID- 2582466 TI - [Mutagenic activity of paracetamol. A study in volunteers]. AB - Mutagenic activity of paracetamol (PC) was studied in a group of healthy persons (3 men, 8 women) after a simultaneous administration of 3 x 1000 mg of PC and of identical dose of PC + 1000 mg of ascorbic acid within an 8 hr. period. Blood sample tests were made at intervals 0, 24, 72 and 168 hrs. Cytogenetic analysis showed that in 24 hrs. the PC increases the aberrant cell frequency to the value of 2.77 +/- 0.37 percentage vs. 1.68 +/- 0.30% (p less than 0.05) prior to the administration of the drug. In 72 hrs., the occurrence of micronucleoli in the buccal mucosa increased to 0.38 +/- 0.07% vs. 0.19 +/- 0.06% prior to PC administration (p less than 0.01). Unscheduled DNA synthesis in peripheral lymphocytes decreased to T/C = 2.06 +/- 0.54 (p less than 0.01) compared to the value of T/C = 3.16 +/- 0.84 before PC administration. The lipid peroxidation level in the plasma was unchanged. The ascorbic acid administered simultaneously with the PC had no effect on the changes observed. The authors recommend a further follow-up of other side PC effects. PMID- 2582467 TI - [Mechanical irrigation and selective decontamination in critically ill patients]. AB - The authors debugged and launched into routine operation an automated monitoring system using computer techniques. Working off-line, they monitored microbiological, immunologic and biochemical parameters of mechanical irrigation of the mouth and selective decontamination of the gastro-intestinal tract. They ran and classified the data concerned into two index-sequence subsets defined on a set of patients treated with artificial pulmonary ventilation and patients with reduced defenses, and/or corticoid-dependent patients with myasthenia gravis. At present, they study basic sets, representative enough to permit the statistically significant examination of all the parameters under study as well as their exact interpretation with regard to the efficiency of the therapeutical strategy chosen. PMID- 2582468 TI - [Intensive post-remission therapy of acute myeloid leukemia with high doses of cytosine arabinoside]. AB - The results are estimated of treatment for acute myeloid leukaemia using intensive post-remission therapy with high doses of cytosine arabinoside (HiDAC). Two women and four men aged 18-34 years were treated with HiDAC. None of them had been given maintenance or boost chemotherapy any more at the time. The patients were rated for the duration of granulocytopenia and thrombocytopenia for the incidence of non-haematological complications and for the duration and quality of survival. The preliminary results are promising and in keeping with those reported by similar clinical centres abroad, namely that maintenance therapy should be phased out in the presence of intensive post-remission treatment. PMID- 2582469 TI - [Metastasizing melanoma]. AB - The complexities of diagnosing melanoma metastases are discussed. More accuracy can be attained with the aid of USG, CT, NMR and scintiscans of the liver. The LDH test appears to be the most effective in cases of metastases developing in the liver. A case of melanoma metastases in the gallbladder is analyzed. PMID- 2582470 TI - [Iatropathogenic effect of Mevacor on vitamin D metabolism]. AB - The authors examined 18 heterozygotes with familial hypercholesterolaemia and assessed vitamin D metabolites, parameters of phosphocalcium homeostasis and blood lipids. They investigated the effect of the hypolipidaemic drug lovastatin (Mevacor, Merck, Sharpe Dohme, tbl. 20 mg) on the vitamin D metabolism, using increasing doses of 20 to 80 mg per day. They found normal parameters of phosphocalcium homeostasis, normal plasma concentrations of 1,25-dihydroxyvitamin D but low basal values of 25-dihydroxyvitamin D and elevated plasma levels after three months' treatment with MEVACOR. They confirmed at the same time the hypocholesterolaemic effect of the drug. The authors conclude that heterozygotes with familial hypercholesterolaemia may suffer from vitamin D deficiency and that the positive iatropathogenic effect of MEVACOR, a substance inhibiting the activity of 3 hydroxymethylglutarate coenzyme A reductase can have a supporting effect on the vitamin D homeostasis, in particular in old people with vitamin D deficiency. PMID- 2582471 TI - [Treatment of anemia in patients on a regular dialysis program using human recombinant erythropoietin]. AB - Five women aged 50-64 years with chronic renal failure, due to interstitial nephritis, enlisted in a regular dialyzation programme were treated for three months with human recombinant erythropoietin. The blood haemoglobin level rose from 78.0 +/- 6.9 g/l to 108.4 +/- 15.5 g/l, the haematocrit from 21.8 +/- 1.8% to 33.6 +/- 4.9%. The serum ferritin concentration declined from 2213 +/- 1892 micrograms/l to 850 +/- 953 micrograms/l. Contrary to the period before treatment, during erythropoietin administration no blood transfusion had to be administered. The general condition of the patients improved. There were no serious complications. The action of erythropoietin persisted for two months. Human recombinant erythropoietin is significant help in the treatment of patients with chronic renal failure. PMID- 2582472 TI - [Changes in blood pressure and erythrocyte sodium transport in subjects with normal blood pressure after dietary sodium loading]. AB - The authors investigated in 20 healthy normotonics changes of the blood pressure and sodium transport in red cells after two dietary regimes: I. normal diet, II. normal diet + 5 g salt/day for a period of 7 days. After the salt load the following changes were observed: 1. a rise of the pressure and body weight 2. an increase of the mean blood pressure (MBP) by more than 7% in 11 subjects, described as "salt sensitive" (SS), the remaining 9 were not sensitive to salt (NSS); 3. a significant activation of ouabain sensitive transport (Na pump) in NSS. The authors did not observe a reduced activity of the Na pump found in volume expansion in essential hypertonics. On the other hand, after the salt load in normotonics an adaptive increase of the Na pump activation occurred which, however, was not sufficient in VSS normotonics. The authors assume that an inadequate response of the Na pump to a salt load in SS may be due to structural changes of the pump or its inadequate functional reserve which may be genetically conditioned and may lead secondarily to an increased salt sensitivity. PMID- 2582473 TI - [Do the algae known as "Japanese crystals" have a therapeutic effect?]. PMID- 2582474 TI - Stage-specific localization of cytoskeletal actin mRNA in murine seminiferous tubules and intestinal epithelia as demonstrated by in-situ hybridization. AB - In-situ hybridization experiments have been performed using isoactin (beta and gamma)-specific riboprobes in various tissues of the rat and mouse. Distribution of the grains of actin mRNAs for both beta and gamma types was similar throughout sections of the rat testis. Although both mRNAs were evenly distributed in the seminiferous tubule, extremely heavy labeling was observed in about 10% of the seminiferous tubules that could be identified as stage XII of spermatogenesis. At high magnification, grains of the mRNA were found in the cytoplasm of elongating spermatids and in the Sertoli cell cytoplasm at the adluminal side. Much higher density of the grains of mRNA was observed in the neck region of the spermatids at stage XII. Thus, the dense distribution of cytoskeletal actin mRNAs is stage specific in the tubule during spermatogenesis in the rat. The high expression of both beta and gamma actin mRNAs was also observed in the epithelial cells of the intestinal crypts. PMID- 2582475 TI - Embryonic chicken retinal cells can regenerate all cell layers in vitro, but ciliary pigmented cells induce their correct polarity. AB - The capacities of retinal and pigmented cells to regenerate histotypic in-vitro retinae (IVR) in rotary culture were investigated by dividing the eye cups of 6 day-old chicken embryos into a central and a peripheral part; they were cut along the ora serrata, and the retinal and the pigmented constituents of both parts were isolated. The 4 dissociated cell populations were cultured separately and in all double combinations. Two different types of IVR's were generated; one developed from central or peripheral retinal cells, the other required the addition of pigmented cells from the ciliary margin of the eye. The shape of these IVR's was examined using scanning electron microscopy, and they were also characterized histologically. The acetylcholinesterase pattern marked the inner half of the retina; F11-antibody and a peanut agglutinin marker revealed both plexiform layers and a radial fiber system. In both types, organized histotypical areas consisted of complete sets of retinal layers. In the type containing pigmented cells from the eye periphery, the sequence of layers was identical with that of an in-situ-retina ("laminar IVR"). In IVR's derived from retinal cells only, the sequence of layers was reversed ("rosetted IVR"). PMID- 2582476 TI - System-specific distribution of zinc in the chick brain. A light- and electron microscopic study using the Timm method. AB - The brain of young domestic chicks was investigated using a Timm sulfide silver method. Serial Vibratome sections were analyzed under the light microscope, and the localization of zinc-positive structures in selected areas was determined at the ultrastructural level. Both strong and differential staining was visible in the avian telencephalon whereas most subtelencephalic structures showed a pale reaction. The highest staining intensity was found in the nonprimary sensory regions of the telencephalon such as the hyperstriatum dorsale, hyperstriatum ventrale, hippocampus, palaeostriatum augmentatum, lobus parolfactorius and caudal parts of neostriatum. There was an overall gradient of staining intensity in neostriatal areas from rostral to caudal with the heaviest zinc deposits in the caudal neostriatum. Primary sensory projection areas, such as the ectostriatum (visual), hyperstriatum intercalatum superius (visual), nucleus basalis (beak representation), the input layer L2 of the auditory field L and the somatosensory area rostral to field L were selectively left unstained. Fiber tracts throughout the brain were free of zinc deposits except for glial cells. In electron micrographs of stained regions, silver grains were localized in some presynaptic boutons of asymmetric synpases (Gray type I), within the cytoplasm of neuronal somata and sporadically in the nucleus. The possible involvement of zinc in synaptic transmission and other processes is discussed. PMID- 2582477 TI - Peptide-containing nerve fibers in the respiratory tract of the ferret. AB - The ferret is widely used in functional and neuromorphological studies on the respiratory tract. We have examined the occurrence and distribution of peptide containing and adrenergic nerve fibers (using dopamine-beta-hydroxylase as a marker). Adrenergic nerve fibers and fibers storing vasoactive intestinal peptide have a widespread distribution along the entire respiratory tract. Adrenergic nerve fibers were found in the lamina propria, as well as around blood vessels and glands and in smooth muscle. Nerve fibers storing vasoactive intestinal peptide occurred in the epithelium, the lamina propria, around blood vessels and glands, and among muscle bundles. Substance P-, neurokinin A- and calcitonin gene related peptide-containing nerve fibers predominated beneath and within the epithelium along the entire respiratory tract. Neuropeptide Y-containing nerve fibers were prominent among smooth muscle bundles and around glands. The blood vessels in the wall of the airways were richly supplied with peptide-containing nerve fibers and adrenergic fibers. Ganglia located over the outer or dorsal surface of the tracheal wall harbored vasoactive intestinal peptide-containing nerve cell bodies. Substance P and neurokinin A invariably coexisted in the same nerve fibers. Further, coexistence of substance P/neurokinin A and calcitonin gene-related peptide was observed in the nerve fibers associated with the epithelium. Vasoactive intestinal peptide, neuropeptide Y and occasionally also substance P coexisted in the population of nerve fibers associated with blood vessels and smooth muscle. Many adrenergic nerve fibers contained neuropeptide Y. PMID- 2582478 TI - Intramembrane particles and filipin labelling on the membranes of autophagic vacuoles and lysosomes in mouse liver. AB - Morphologically detectable protein (intramembrane particles) and cholesterol (filipin labelling) in the membranes of autophagic vacuoles and lysosomes were studied in mouse hepatocytes using thin-section and freeze-fracture electron microscopy. Both isolated autophagic vacuoles and lysosomes, and intact tissue blocks were used due to the facts (i) that lysosomes are difficult to recognize in freeze-fracture replicas of intact hepatocytes, and (i) that filipin penetration into the tissue blocks is unsatisfactory. Intramembrane particle density was low in the membranes of early autophagic vacuoles (defined as round shaped vacuoles in which an inner membrane parallel with the outer limiting membrane was clearly visible). The lysosomal membranes contained considerably more intramembrane particles. Particle-rich lysosomes or other vesicles were observed to fuse with the early autophagic vacuoles. The membranes of nascent autophagic vacuoles with morphologically intact contents were usually not labelled by filipin, whereas the membranes of all other autophagic vacuoles and lysosomes were heavily labelled. The increased cholesterol in the membranes of slightly older autophagic vacuoles is presumably derived from cholesterol-rich lysosomes or other vesicles fusing with the vacuoles and from the degrading organelles inside the autophagic vacuoles. PMID- 2582479 TI - Localization of cholesterol in the colonic epithelium of the guinea pig: regional differences and functional implications. AB - It is generally accepted that variations in membrane cholesterol content affect the fluidity of the bilayer, thus altering its permeability. In the biological membranes, in physiological conditions, a high cholesterol content rigidifies the bilayer decreasing its permeability, a lower cholesterol content induces the opposite effect by increasing the permeability. Since differences in the epithelial permeability for short chain fatty acids have previously been demonstrated in the proximal and distal colon of the guinea pig, these two regions were investigated to establish whether differences in membrane cholesterol content of the absorbing cells can be demonstrated. Freeze-fracture replicas of filipin-treated colonic tissue were used. The results show that in the proximal colon the density of filipin cholesterol complexes located on the luminal plasma membrane of the columnar absorbing cells was significantly higher (about twice) than in the distal colon. Therefore the lower amount of cholesterol present in the membrane of the absorbing cells in the distal colon indicates a greater fluidity of the membranes of the epithelial cells in this region. Such fluidity could be correlated to the higher absorption rates of shortchain fatty acids characteristic of this region. PMID- 2582480 TI - The distribution of endocrine cells in the mucosa of the gastrointestinal tract of the house musk shrew, Suncus murinus (Insectivora). AB - The distribution of endocrine cells in the gastrointestinal tract of the house musk shrew, Suncus murinus (Family Soricidae, Order Insectivora) was studied immunohistochemically. The hormones investigated were gastrin, cholecystokinin (CCK), somatostatin, secretin, glucagon, gastric inhibitory polypeptide (GIP), motilin and neurotensin. In the gastric mucosa, gastrin and somatostatin cells were only found in the pyloric regions, and no other hormonal cell-types were observed. In the intestinal mucosa, the largest number of endocrine cells belonged to the gastrin and glucagon/glicentin cell-types, whereas CCK-33/39 and secretin cells were the least numerous. Numbers of other cell-types were intermediate between these two groups. The gastrin and GIP cells were mostly localized in the proximal portion of the intestine, decreasing in number towards the distal portion. The motilin and CCK-33/39 cells were restricted to the proximal half. The glucagon/glicentin and neurotensin cells were most abundant in the middle portion. The somatostatin and secretin cells, although only present in small numbers, were randomly distributed throughout the intestine. This characteristic distribution of gastrointestinal endocrine cells is discussed in comparison with the distribution patterns of other mammals. PMID- 2582482 TI - Dynamic changes of cell-surface glycoconjugates in human palmar epidermis following friction-blisters. AB - Damage and repair of cell-surface glycoconjugates were examined in human palmar skin following friction-blister injury, using biotinylated lectins and the avidin biotin complex method. In normal skin, concanavalin A, Ricinus communis, and Triticum vulgaris bound to the surface of cells from the basal layer to the granular layer. After injury, binding of concanavalin A was absent in the plasma membrane, but appeared in the cytoplasm at perinuclear sites. The surface reaction was recovered in basal and spinous cells, but not in granular cells, when cell maturation began at 5 days after injury. In contrast, binding of Ricinus communis and Triticum vulgaris was, in general, much more resistant to tissue damage. Even in some cells, where the surface staining became obscure at an early period, a normal staining pattern reappeared by 6 h after injury. Staining of Ulex europeus I and Glycine max, detected on the surface of upper spinous and granular cells in normal skin, disappeared immediately after the injury, but recovered quickly on the surfaces of the differentiated cells. These findings suggest that at least 2 oligosaccharide sequences, one binding with concanavalin A, and the other with Ricinus communis and Triticum vulgaris, may exist on epidermal cells. Addition of terminal carbohydrates, detectable with binding of Ulex europeus I and Glycine max, appears to occur on the Ricinus communis I and Triticum vulgaris-bound oligosaccharide chain. PMID- 2582481 TI - The effect of thioglycolate on intermediate filaments and membrane translocation in rat urothelium during the expansion-contraction cycle. AB - The functional role of cytokeratin intermediate filaments in the translocation of asymmetric membrane plaques between cytoplasm and surface of apical urothelial cells was investigated during contraction and expansion of rat urinary bladders. A stereological investigation of electron micrographs provided estimations of surface area, volume, and number of discoidal vesicles and infoldings per unit volume of urothelial apical cell cytoplasm. Contracted and distended bladders incubated in 0.01 M sodium bicarbonate were compared to identical preparations experimentally incubated in 5 mM thioglycolic acid. The latter reagent disrupts the intermediate filament network by reducing sulfhydryl bridges. Densities of discoidal vesicles in cells contracted after incubation in thioglycolate were similar to density estimations in cells expanded under control conditions. Similarly, densities of vesicles in cells expanded after exposure to thioglycolate were comparable in number to those in normally contracted cells. Thus, membrane translocation to and from the luminal surface was blocked by thioglycolate treatment. The lack of normal membrane transfer at the luminal surface induces apical cells exposed to experimental conditions to undergo extraordinary adjustments in response to external pressures of bladder contraction and distension. During contraction, the apical-intermediate cell interface unfolded while the luminal surface ballooned out into the lumen. In distended bladders, large intercellular spaces formed between apical cells along their lateral margins. The results support a model published earlier implicating the filament network as a critical mediator of membrane translocation. PMID- 2582483 TI - Vascular response in a non-uterine site to implantation-stage embryos following interspecies transfers between the rat, mouse, and guinea-pig. AB - Pre-implantation-stage embryos from rats, mice, and guinea-pigs were transferred to a non-uterine site--the anterior chamber of the eye--of female recipients. All 9 combinations of transfers were performed: 3 allogeneic (intraspecies) transfers as controls, and 6 xenogeneic (interspecies) transfers. Implantation, as judged by extravasation from blood vessels of the iris or ciliary body occurred with success rates of 90.4% per transfer in the control rat group. 76.9% in the control mouse group, and 81.8% in the control guinea-pig group. Significantly reduced implantation rates occurred in the rat to guinea-pig (0%), mouse to rat (46.9%), mouse to guinea-pig (6.7%), and guinea-pig to rat (0%) groups compared to controls. Reductions, although not significant, also occurred in the other 2 groups: rat to mouse (77.8%), and guinea-pig to mouse (44.4%). These results together with some ultrastructural and light-microscopical observations suggest a degree of species specificity involved in the vascular response to the implanting embryo. We propose that the peri-implantation embryo produces a signal(s) which is to some extent species specific and which in the normal allogeneic situation is responsible for the early vascular effects seen at implantation in most eutherian mammals. PMID- 2582484 TI - Innervation of the arteriovenous anastomoses in the dog tongue. AB - Profiles of nerve plexuses in the arteriovenous anastomoses of the dog tongue were investigated by both transmission and scanning electron microscopy. Three dimensional morphology of the vascular nerves was examined after removal of the connective tissue components by the HCl-hydrolysis method. Tight bending and a rich nerve supply were the most characteristic features of the anastomosing channels. The tunica media consisted of an outer circular layer of typical smooth muscle cells and an inner region containing longitudinal plicae of ramified smooth-muscle cells. The tunica adventitia was exclusively occupied by nerve bundles; fibroblasts were poorly developed. Numerous nerve bundles of variable size were coiled around the anastomosing channels, and occasional bundles ran crosswise over the U-shaped bent vessels. PMID- 2582485 TI - Ectopic Purkinje-like cells are GABAergic: immunohistochemistry with an immune serum against glutamic acid decarboxylase. AB - Intensely stained cells are found in the cerebellar white matter of the vermis and paravermis in adult rats after immunoreaction with an immune serum raised against glutamic acid decarboxylase (GAD). The cells are similar in size to cortical Purkinje cells and three times the size of Golgi cells of the internal granule layer, and have a thick immunopositive cell process emerging from a well defined cytoplasmic cone. In the cytoplasm, immunoprecipitates are more dense around the nucleus as in normally located Purkinje cells. The morphological appearance of the immunopositive cells suggests that they may be ectopically located Purkinje cells. The soma of the ectopic Purkinje cells is contacted by a few darkly stained terminal boutons. Data indicate that, in spite of the different cellular environment, ectopic Purkinje cells can develop not only the typical morphological pattern already described but also other intrinsic features, such as their typical inhibitory neurotransmitter. PMID- 2582486 TI - Effect of non-steroidal anti-inflammatory agents on the upper gastro-intestinal tract: gastroscopic findings in Nigerians. AB - The effect of 4 non-steroidal anti-inflammatory agents, viz Aspirin, Piroxicam, Ibuprofen and Indomethacin on the gastric mucosa of the African was studied on 34 volunteers who had no previous symptoms of acid peptic diseases. Aspirin caused the worst lesions while piroxicam caused the least lesions. The indiscriminate prescription of these drugs, particularly drugs containing acetosalicylic acid should be avoided. PMID- 2582487 TI - Helminth ova in soil from children's playgrounds in Calabar, Nigeria. AB - A study was undertaken to examine the helminth ova in soil from children's playgrounds in Calabar, Nigeria. A total of 150 soil samples were collected from the playgrounds studied. Ova of Ascaris lumbricoides (10 percent, 12 percent and 20 percent) were found in these playgrounds. In addition, each of the following helminth ova was found respectively in each of the playgrounds: Trichuris vulpis (4 percent), Toxocara canis (8 percent) and Strongyloides stercoralis (6 percent). The public health aspects of these findings are discussed. PMID- 2582488 TI - Some applications of the tensor fascia lata myocutaneous flap. AB - Two cases of reconstruction using the Tensor Fascia (TFL) myocutaneous flap are presented. In the first case the T F L flap was used to resurface a complex soft tissue defect on the extensor surface of the left forearm. The T F L flap was used in the second case to resurface a left trochanteric bedsore in a patient recovering from paraparesis sustained from an attack of Transverse Myelitis. The flap was successfully used in both cases. PMID- 2582489 TI - Identification of an octapeptide involved in homophilic interaction of the cell adhesion molecule gp80 of dictyostelium discoideum. AB - During development of Dictyostelium discoideum, a surface glycoprotein of Mr 80,000 (gp80) is known to mediate EDTA-resistant cell-cell adhesion via homophilic interaction. Antibodies directed against a 13 amino acid sequence (13 mer) near the NH2 terminus of the protein were found to inhibit cell reassociation. This 13-mer also inhibited gp80-cell interaction and gp80-gp80 interaction. The cell binding site was mapped to the octapeptide sequence YKLNVNDS by using shorter peptide sequences to inhibit gp80 interaction. High salt concentrations inhibited homophilic interactions of both the 13-mer and gp80, suggesting that ionic interactions are involved in the forward binding reaction. Since disruption of homophilic interactions between the bound molecules required the presence of Triton X-100, hydrophobic interactions may occur after the initial ionic binding. PMID- 2582490 TI - The lck tyrosine protein kinase interacts with the cytoplasmic tail of the CD4 glycoprotein through its unique amino-terminal domain. AB - The CD4 lymphocyte surface glycoprotein and the lck tyrosine protein kinase p56lck are found as a complex in T lymphocytes. We have defined the domains in both proteins that are responsible for this interaction by coexpressing hybrid and deleted forms of the two proteins in HeLa cells. We have found that the unique 32 amino-terminal residues of p56lck and the 38 carboxy-terminal residues of CD4 that comprise the cytoplasmic domain are both necessary and sufficient by themselves for the interaction of the two proteins. The interaction appears to be independent of other T cell-specific proteins and probably occurs before CD4 reaches the cell surface. Our findings suggest that the specialized amino terminal domains of other members of the src family of intracellular tyrosine kinases may also mediate transmembrane signaling via coupling to the cytoplasmic domains of specific transmembrane proteins. PMID- 2582491 TI - Alpha beta lineage-specific expression of the alpha T cell receptor gene by nearby silencers. AB - T cells expressing either the alpha beta or gamma delta antigen receptor (TCR) are distinct cell lineages. The single locus encoding the TCR alpha and delta genes requires special regulation to avoid alpha gene expression in gamma delta T cells. We show here that the minimal alpha enhancer is active in the gamma delta T cell lineage but gains alpha beta lineage specificity through negative cis acting elements 3' of the C alpha gene that silence the enhancer in gamma delta T cells. The negative elements at the C alpha locus consist of several silencers that work in an orientation- and distance-independent fashion. These silencers also act on a retroviral enhancer that is normally ubiquitously expressed, restricting its activity to alpha beta cells. The alpha silencers are active in non-T cell lines, suggesting that the decision of a cell to differentiate into the alpha beta T cell lineage may involve specific relief from these silencers. Silencers are likely to be as important as enhancers in establishing lineage specific gene expression in many systems. PMID- 2582492 TI - Assembly and self-association of oxytricha telomeric nucleoprotein complexes. AB - Two types of specific telomeric protein-DNA complex are reconstituted upon incubation of purified Oxytricha telomere protein with (T4G4)4, an oligodeoxynucleotide of telomeric sequence. The complexes differ in electrophoretic mobility, in protein-DNA contacts, and in the rate of DNA exchange. The patterns of protein-DNA interaction determined by modification interference suggest a model in which the protein can bind either to the two T4G4 repeats at the 3' end or to two internal repeats; in the latter case, it can make a different set of contacts with the terminal repeat to form the more stable complex. Native telomeric chromatin isolated from Oxytricha contains both types of complexes. The reconstituted monomeric complexes associate to give a high molecular weight form that has an altered chemical footprint. Such interactions may mediate the association of chromosomal telomeres in vivo. PMID- 2582493 TI - Distribution of the wingless gene product in Drosophila embryos: a protein involved in cell-cell communication. AB - wingless, a segment polarity gene required in every segment for the normal development of the Drosophila embryo, encodes a cysteine-rich protein with a signal peptide. A polyclonal antiserum localizes the wingless protein in approximately the same region of the embryo as the wingless mRNA. The pattern of antigen localization changes rapidly during development. In the extended germband stage, stripes of wingless staining are present in the trunk region just anterior to the parasegment boundary; wingless-expressing cells abut engrailed-expressing cells across that boundary. wingless antigen is seen both inside and outside the cell by electron microscopy: inside the cell, in small membrane-bound vesicles and in multivesicular bodies; outside the cell, close to or on the plasma membrane and associated with material in the intercellular space. The multivesicular bodies containing the wingless protein are occasionally found in engrailed-positive cells, suggesting that the wingless protein behaves as a paracrine signal. PMID- 2582494 TI - The Drosophila patched gene encodes a putative membrane protein required for segmental patterning. AB - The patched (ptc) gene is one of several segment polarity genes required for correct patterning within every segment of Drosophila. The absence of ptc gene function causes a transformation of the fate of cells in the middle part of each segment so that they form pattern elements characteristic of cells positioned around the segment border. Analysis of the mutant phenotype demonstrates that both segment and parasegment borders are included in the duplicated pattern of ptc mutants. We have cloned the ptc gene and deduced that the product is a 1286 amino acid protein with at least seven putative transmembrane alpha helices. ptc RNA is expressed in embryos in broad stripes of segmental periodicity that later split into two stripes per segment primordium. The pattern of expression does not directly predict the transformation seen in ptc mutant embryos, suggesting that ptc participates in cell interactions that establish pattern within the segment. PMID- 2582495 TI - Molecular genetic approaches to protein structure and function. Applications to cell and developmental biology. PMID- 2582496 TI - Relationship between tektins and intermediate filament proteins: an immunological study. AB - Affinity-purified antibodies raised against three flagellar tektins (tektin A, B, and C) from each of two sea urchin species (Lytechinus pictus and Strongylocentrotus purpuratus) were used to study the immunological relationship between tektins and intermediate filament proteins. By immunofluorescence microscopy, several antitektins revealed a staining of intermediate filament-like arrays in three vertebrate cell lines tested. Immunoelectron microscopy substantiated the cross reaction of antitektins with intermediate filaments. When the cells were treated with cytochalasin B, the arrangement of the filaments recognized by anti-(Lp)-tektin B was altered; the alteration observed is typical for keratin filaments. By immunoblot, it was found that anti-(Lp)-tektin B cross reacted with two isoforms or different proteins of approximately 54 kD with pIs of 6.1 and 6.2 in human carcinoma epithelia (HeLa) cells and with two isoforms or different proteins of approximately 55 kD with pIs of 6.1 and 6.3 in pig kidney epithelia (LLC-PK1) cells. Furthermore, when antitektin antibodies were affinity purified with the 54 kD HeLa keratin, these keratin-specific antibodies again restained the original tektins on immunoblots. From these observations, it can be concluded that tektins and keratins are to a certain extent immunologically related. To determine the degree of the immunological relationship, tektin filaments and purified intermediate filaments from HeLa cells were cleaved with alpha-chymotrypsin and examined by quantitative immunoblot analysis. On immunoblots of digested tektins from L. pictus, anti-(Lp)-tektin B recognized several cleavage products in the range of 20 kD to 46 kD. However, when immunoblots of digested intermediate filaments from HeLa cells were probed, the cross reaction of anti-(Lp)-tektin B with HeLa keratins was eliminated by more than 98% within 2 min, suggesting that tektins have epitopes in common with the end domains of certain keratins. PMID- 2582497 TI - Morphology of fibroblasts in collagen gels: a study using 400 keV electron microscopy and computer graphics. AB - We have used 400 kilovolt intermediate voltage electron microscopy (IVEM) to examine thick sections of fibroblasts cultured in collagen gels. In these 3D collagen lattices, the long, narrow pseudopodial extensions that extend out and make contact with the collagen matrix exhibit a complex topography not seen in the processes put out by cells moving on planar substrata. For this reason, sections 1 to 2 microns thick that enclose a whole cell process are more informative of the overall morphology of the interaction between cells and the collagen than are thin sections. To aid the discrimination of topography of cell processes in stereo views of micrographs, some cells were labeled with antibodies and protein A-colloidal gold conjugates. The gold particles provided clear 3D reference points for computer-aided reconstructions of membrane topography from tilt series of IVEM images. Our results confirm that cells that move through collagen lattices lack the well-spread morphology of their counterparts moving on glass. They are generally rather spindly with several long branching anterior pseudopodia. We found that the cell bodies and major pseudopodial processes were cylindrical, as one might expect of cells in a 3D environment, but at the leading edge of advancing pseudopodia there are small flat extensions similar to those seen in cells on glass. This similarity suggests that the lamellipodium is a basic type of protrusive structure used by fibroblasts during locomotion on all types of substratum. The flattened shape of lamellipodia may be part of the mechanism by which cells sense the orientation of fibrillar extracellular matrices during embryonic morphogenesis. PMID- 2582499 TI - External mechanical control of the timing of bend initiation in sea urchin sperm flagella. AB - The movement parameters of a sea urchin sperm flagellum can be manipulated mechanically by applying various modes of periodic vibrations to the sperm head held by suction in the tip of a micropipette. The beat frequency of the flagellum readily synchronizes with the frequency of the externally imposed lateral vibration, and the plane of flagellar bending waves adapts itself to the plane of the pipette vibration (Gibbons et al., J. Cell Biol. 101:270a, 1985; Nature 325: 351-352, 1987). In this study, we observed the particular effects of external asymmetric forces on flagellar beating parameters by vibrating the micropipette holding the sperm head in a transverse sawtooth-like motion composed of a rapid effective stroke and a slower recovery stroke, while keeping the vibration frequency constant. The results demonstrate that the timing of bend initiation within the flagellar beat cycle can be controlled mechanically by changing the time point within the vibration cycle at which the micropipette changes its direction of motion. A switch in the sidedness of the asymmetric movement of the micropipette produces dramatic changes in the profiles of bend growth in the basal 5 microns of the flagellum but has almost no effect on the asymmetry or other parameters of bending in the mid- and distal regions of the flagellum. Our results suggest that elastic strain within the basal region of the flagellar structure may play a more significant role in the process of bend initiation than has been realized heretofore. PMID- 2582498 TI - Isolation of a subpellicular microtubule protein from Trypanosoma brucei that mediates crosslinking of microtubules. AB - The cell body of Trypanosomatidae is enclosed in densely packed, crosslinked, subpellicular microtubules closely underlying the plasma membrane. We isolated the subpellicular microtubules from bloodstream Trypanosoma brucei parasites by use of a zwitterion detergent. These cold stable structures were solubilized by a high ionic strength salt solution, and the soluble proteins that contained tubulin along with several other proteins were further fractionated by Mono S cation exchange column chromatography. Two distinct peaks were eluted containing one protein each, which had an apparent molecular weight of 52 kDa and 53 kDa. (Mr was determined by SDS-gel electrophoresis). Only the 52 kDa protein showed specific tubulin binding properties, which were demonstrated by exposure of nitrocellulose-bound trypanosome proteins to brain tubulin. When this protein was added to brain tubulin in the presence of taxol and GTP, microtubule bundles were formed with regular crosslinks between the parallel closely packed microtubules. The crosslinks were about 7.2 nm apart (center to center). Under the same conditions, but with the 53 kDA protein or without trypanosome derived proteins, brain tubulin polymerized to single microtubules. It is thus suggested that the unique structural organization of the subpellicular microtubules is dictated by specific parasite proteins and is not an inherent property of the polymerizing tubulin. The in vitro reconstituted microtubule bundles are strikingly similar to the subpellicular microtubule network of the parasite. PMID- 2582500 TI - [Personal experience with monitoring drug prescriptions in pregnancy]. AB - The authors submit the results of an epidemiological perspective investigation concerned with drug prescription in 372 pregnant women during the period 1983 1988 in two municipal health communities of a regional town with an industrial and agricultural agglomeration. They record for orientation also some other factors which may have an impact on mother and foetus, i.e. smoking, alcohol intake, black coffee. In drugs with a possible negative effect on mother and foetus the prescribed dose was expressed in % DDD and the time interval during pregnancy. The results revealed a significant drop of drug prescription in all groups of drugs, in particular Ferronat, antihistaminic drugs and Diazepam. Perinatal complications, functional or somatic disorders in neonates were manifested in 31% of the total number of neonates. In the small group investigated by the authors neither the effect of the number of drugs nor a relationship between different drugs and certain functional or somatic disorders of the child during delivery were apparent. PMID- 2582502 TI - [Functional reserve of umbilico-placental circulation]. AB - The authors present the results of the action of 10% magnesium sulphate on the umbilico-placental circulation. They found that intravenous administration of magnesium sulphate reduces the vascular resistance in the umbilico-placental circulation and improves its parameters when a functional disorder is involved. The maximum effect was recorded during the 10th minute following administration. In case of absolute reduction of the placental circulation or in case of an obstruction in the umbilical artery the above parameters did not improve. Magnesium sulphate administration may serve as a loading test of the functional reserve of the umbilico-placental circulation. PMID- 2582501 TI - [Routine screening for serological markers of viral hepatitis B in pregnancy]. AB - Transmission of hepatitis B virus (HBV) from mother to infant during the perinatal period represents very efficient mode of HBV infection and often leads to severe longterm sequelae. Perinatal transmission can occur when an infant is born to mother positive for hepatitis B surface antigen (HBsAg), frequency of transmission is high if the mother is also HBeAg positive. Prevention of perinatal transmission of HBV is important since the majority of these infants who are infected at birth become chronic carriers and can subsequently develop chronic hepatitis, cirrhosis or primary hepatocellular carcinoma. Routine screening for HBsAg of all pregnant women attending prenatal clinic at the Institute for the Care of Mother and Child, Prague in the third trimester of pregnancy by Sevatest ELISA HBsAg Micro I. method (Sevac, Prague) began in June 1986. HBsAg positive patients were subsequently tested for HBeAg and anti-HBe hepatitis markers. Of the 2744 women examined 22 were found HBsAg positive, of these mostly asymptomatic carrier mothers 2 were positive for HBeAg, 14 for anti HBe and 6 were negative for both HbeAg and anti-HBe. All infants were given passive HBIg prophylaxis in conjunction with HB vaccine after birth regardless of HBeAg status of mother. At present no infant were found HBsAg positive at 6 month of age, observation of this risk group infants continues. PMID- 2582503 TI - [Semi-ambulatory genetic amniocentesis]. PMID- 2582505 TI - [The past and future of cardiotocography in Czechoslovakia]. PMID- 2582504 TI - [The importance of electromyography of the external urethral sphincter muscle in the diagnosis of urinary incontinence in women]. PMID- 2582506 TI - [What are the present views on indications for cesarean section?]. PMID- 2582508 TI - [Physiology and pathology of the puerperium. Selected papers presented at the national scientific conference of the Slovak Gynecologico-Obstetrical Society. Bratislava, 8-9 December 1988. Abstracts]. PMID- 2582507 TI - [The status of perinatal care and its results in Czechoslovakia in 1987]. PMID- 2582509 TI - [Multiple tumors in patients with laryngeal cancer]. AB - The author evaluated a group of patients treated on account of carcinoma of the larynx in 1958-1977 and followed up till 1988. A second primary tumour except to that of the larynx and skin was detected in 1978 in 5.5% of the patients, in 1983 in 10.0%, and in 1988 in 12.6%. Before the complete extinction of the group due to deaths of its members it may be assumed that multiple tumours will reach 17%. 44% of the multiple tumours were carcinomas of the lungs and 43% carcinomas of the digestive tract. Follow-up of patients after treatment of carcinoma of the larynx must concentrate attention among others also on organs with a high probability of tumour multiplicity. PMID- 2582510 TI - [Hearing in patients with chronic otitis media and cholesteatoma]. AB - The authors submit their experience with the treatment of chronic otitis media with cholesteatoma and inform on therapeutic results recorded in 1979-1986. Chronic otitis media with cholesteatoma are encountered still relatively frequently. The authors detected it in adults in 40%. In children and adolescents under 20 years the percentage incidence is even higher, 53%. In a group of 38 operated patients the authors investigated the preoperative findings, the type of auditory disorder and its extent. They investigated also the selection of operations and reconstruction operations. The auditory gains were correlated with the percentage occlusion of the cochlear reserve, subjective data on altered hearing, disappearance of tinnitus and discharge from the ear. In children and adolescents a 22% auditory gain was recorded, in the age group of 21-40 years an auditory gain of 19.20%. In more advanced age groups a loss of 16.4%. Subjective improvement of hearing was reported by 41%, no change by 32%, deterioration by 27% of the patients. Constant tinnitus persisted after operation in 7.9% and a constant discharge in 4.5% of the operated patients. In one instance the authors observed a relapse of cholesteatoma in a patient operated by the so-called "closed method". PMID- 2582511 TI - [ENG findings in 47 acoustic neurinomas]. AB - ENG examinations still belong to the basic examinations in the diagnosis of acoustic neurinomas. The decisive finding in small and medium-sized tumours is a peripheral involutional vestibular symptomatology on the side of the lesion: vestibular caloric hyporeflexia to areflexia, possibly associated with spontaneous nystagmus towards the sound side. In large or giant tumours on the ENG tracing other symptoms caused by compression and pressure on the brain stem and flocculonodular part of the cerebellum are found: visual paretic nystagmus (its variant is Bruns-Stewart's nystagmus), rebound nystagmus, high fixation suppression index, ocular dysmetria (over- or undershoot) and delaging of the eyes during fixation of a moving target, compensated by corrective saccades in tests of continuous tracing of ocular movements, which all provide unequivocal evidence of the size of the tumour. In this way 13 small and medium sized tumours were diagnosed, as well as large tumours (above 2 cm in diameter) and giant tumours (above 4 cm in diameter) a total of 34. In this respect ENG findings were consistent with surgical ones and CT and if any CT cisternographic findings with contrasting air filling. PMID- 2582513 TI - [Microsurgical removal of synechia in the vocal cord area]. AB - The authors submit two recommendations for the final surgical elimination of adhesions between the vocal folds. In both instances the procedure prevents the development of a new adhesion by covering at least one vocal fold by a mucous membrane. The operations are performed by the endolaryngeal route. PMID- 2582512 TI - [Post-traumatic stenoses of the larynx and subglottic space]. AB - The authors give the basic principles of the etiopathogenesis of post-traumatic stenoses of the larynx and subglottic space. Therapeutic tactics are briefly described. Three basic types of treatment are illustrated on their own observations. PMID- 2582514 TI - [Dusodril in the ambulatory care of inner ear disorders]. AB - The author discusses causes of disorders of the internal ear. He describes the tactics of treatment used in his department and gives an account of the therapeutic effect of the drug. In the subsequent parts of the paper results are quoted which were achieved during treatment of a total of 82 ambulatory patients. Dusodril is comparable with other preparations used in disorders of the internal ear. According to the author's observation it influences the symptomatology of the internal ear in the following order: dizziness hypacusia, tinnitus. PMID- 2582515 TI - [Congenital duplication of the external auditory canal]. AB - An anomaly of the external auditory meatus in a two-year-old child manifested by a fistula in the area of the right parotid gland. From the histological aspect a non-epithelized fistula was involved through which cerumen and epithelia accumulating in the closed part of the duplicated external auditory meatus were drained, the latter being discovered only on reoperation of an originally assumed cervicoaural fistula. PMID- 2582516 TI - [Transplantation and regeneration of brain tissue: present state and perspectives]. PMID- 2582518 TI - [Transplantation of the embryonic neocortex into the brain in rats: angioarchitecture of the graft 5 months after surgery]. AB - In five adult rats into a bilateral, two-week old cavity in the sensorimotor cortex a homologous embryonic neocortex was implanted which was removed on the 14th day of gestation. The angioarchitecture was studied after a whole body injection of Indian ink into the host circulation. The regional capillarization in the transplant corresponded to construction principles of the graft. The neuron agglomerations which were arranged in a nodal pattern displayed the same capillary density as surrounding cerebral tissue. In the glial septa and in portions of the glial scar the capillary density was substantially lower. In zone I. representing a complete fusion of the neuropil between graft and recipient there was an inapparent and continuous transition of the capillary network. Also in the area of the glial scar (zone II) and the gliomeningeal scar (zone III) vascular connection was established. PMID- 2582517 TI - [Pathobiology of experimental spinal cord injury (characteristics of the present stage of research)]. PMID- 2582519 TI - [What else does the computerized tomograph of the head reveal? Neuromorphologic approach to cancerogenesis]. PMID- 2582520 TI - [Changes in carbohydrate metabolism before and after the development of focal cerebral ischemia. III. Function of the diencephalon]. AB - The purpose of the investigation was to assess whether the mechanism of reduced glucose tolerance in focal ischaemia of the brain can be considered a functional disorder of the regulatory brain centres or a manifestation of inadequate glucose utilization due to impaired insulin secretion. The function of centres regulating metabolic processes was tested by the i.v. administration of Pyrifer. It was revealed that after Pyrifer administration a parallel rise of the investigated values does not occur (i.e. number of leucocytes, body temperature, pulse, systolic and diastolic pressure, blood sugar level), the maximum values do not reach the levels of the control group, their rise is retarded, persists twice as long as in the control group and does not return to baseline values in the appropriate time. A pathological constellation of responses was recorded in 85.71% of the cases. A similar trend of changes was found also in a group of arteriosclerotic and hypertonic patients although in a lower percentage. The results confirmed the assumption that in the mechanism of reduced glucose tolerance in the periphery an important part is played by the impaired function of regulating centres in the diencephalon. PMID- 2582521 TI - [Genetic linkage of the autosomal dominant form of Charcot-Marie-Tooth amyotrophy and 3 genetic markers on chromosome 1]. AB - In a large pedigree with the autosomal dominant form of Charcot-Marie-Tooth neuropathy type I (CMT 1) segregating in four generations, genetic linkage was studied between this disease and three genetic markers from the centromere region of chromosome 1: Duffy blood group (Fy), salivary and pancreatic isoamylases (AMY 1, AMY 2), and DNA polymorphism at the antithrombin III locus, detected with the probe pAT3c. The lod-scores found do not support linkage between CMT 1 and both Fy and AT 3, since they are negative for all recombination frequencies. Very close linkage could have been excluded. For the AMY polymorphism, the pedigree was not linkage-informative. In agreement with the data from literature, these results support the notion of genetic heterogeneity of CMT 1: in the pedigree under study, the responsible locus is probably not in the centromeric region of the chromosome 1, where it was shown to map to in several other pedigrees. Thus, there seem to exist at least two loci responsible for this type of CMT disease. PMID- 2582522 TI - [Vascular headache. Changes in visual evoked potentials]. AB - The authors examined visual evoked potentials using the method of the visual full field stimulation hemi-field, using a check-board patterned structural stimulus in 69 patients with the diagnosis of vascular headache. The peak latencies of the waves did not differ significantly in the group of patients with vascular cephalea, as compared with the control group; this applies to both ways of stimulation. The es amplitudes of waves (P1 = P100 and N2) were significantly higher in the group with vascular cephalea after stimulation by the visual field. Of half the visual field stimulation did not reveal statistically significant differences in the latencies waves. The results may indicate an increased electrophysiological activity of the visual system in the interparoxysmal period in patients with vascular cephalea. PMID- 2582524 TI - [Recurrent hemorrhage into the mesencephalon]. AB - The author described the case of a 19-year-old man, normotensive, who developed after a blunt injury of the head haemorrhage into the left part of the mesencephalon with the symptomatology Weber's stem syndrome. Manifestation of focal symptoms was recorded three days after the injury. The cerebrospinal fluid examined on the fourth day was normal, cerebrospinal fluid one week later was blood stained. Fourteen months after this primary haemorrhage after almost complete clinical recovery a spontaneous relapse of haemorrhage occurred at the original site with the same symptomatology. Angiography was normal, haemorrhage was proved by CT and its cause was not elucidated. Haemorrhage into the brain stem of normotensive subjects is a rare and special group with a favourable prognosis and it must be differentiated from haemorrhage in hypertonic subjects. PMID- 2582523 TI - [Developmental cysts in the area of the quadrigeminal plate in children]. AB - The authors describe three cases of operated developmental cysts in the area of the laminae quadrigeminae in children. The performed multiple fenestrations or excision of the wall of the cyst and effective communication with the subarachnoid or ventricular system, as well as a plastic operation of the dura mater with collagen tissue from a Tissue bank. By means of light microscopy the walls of two cysts were examined (one arachnoid and one glioependymal), one cyst was examined by electron microscopy (glioependymal). The authors supplemented by their own cases the number of hitherto described cysts in the collicular region to 56. PMID- 2582525 TI - Influenza serosurvey for the 1989-1990 season. Prevalence of antibody to current influenza virus strains in a 1989 Canadian serosurvey. PMID- 2582526 TI - A school outbreak of hepatitis A in southwestern Ontario. PMID- 2582527 TI - Meningococcemia in a group of Canadian students on a European trip. PMID- 2582528 TI - [The development of theoretical bases of health care is one of the most important priorities]. AB - The standard of the theoretical background determines the quality and effectiveness of health care as a nation-wide system. The author draws attention to the necessity of a rapid development of social medicine in the sphere of information, research, training and management. A feasible starting point is the programme of the World Health Organization "Health for All by the Year 2000". PMID- 2582530 TI - [The life style of the Czechoslovak population in relation to health]. AB - The paper is devoted to the development of the life style factors of the Czechoslovak population relevant for health. The author analyzes broader socio economic relations of the shaping of the life style, in particular the developmental stage of production, the structure of national economy and the type of social order. The most important components of the life style, with a negative impact on the health potential are inadequate or one-sided exercise, an unbalanced diet and unfavourable responses to stressing situations (smoking, abuse of alcohol, other types of drug addiction etc.). Reflections on the possible future development of the life style in relation to health are projected into two polar alternatives--warning and intensification. Implementation of the warning alternative would imply further health damage on a mass scale. Only the intensification alternative implemented within the context of the nation-wide strategy of restoration and development of national health would lead at first to slight, later to substantial positive shifts in the health standard of the Czechoslovak population. PMID- 2582529 TI - [Perspectives in the development of health care in Czechoslovakia]. AB - The finding that the health status of the population is shaped in particular by social and cultural conditions is accepted not only by health workers but also by political and executive authorities of the State. For the further development health care of the people is of revolutionary importance. If society will find adequate political will to take the appropriate measures, we may expect radical changes in all spheres of national economy, social life, science and culture. The basic demand is that health workers must acquire new sociomedical thinking which supplements and at the same time replaces the out-dated biomedical pattern. Structural changes will pertain in particular to mechanisms and organizational measures which will ensure the implementation of the health policy beyond the framework of the health services. In the system of health services we may anticipate that the centre of gravity in health care will shift from the traditional hospital to out-patient facilities with emphasis on the newly conceived function of primary health care. Training of health workers will have to be modified to the effect that graduates will be better prepared to meet actual needs of health care focused on prevention, economy, effectiveness and quality. It will be necessary to create favourable conditions for the development of socio-ecological, epidemiological and operational research. The democratization of health care will call for greater interest and initiative on the part of the public as regards collective and individual health. Our partial health projects should be re-arranged into a single comprehensive nation-wide programme which will include all spheres of health care in the sense of the WHO programme in its modification for Europe. PMID- 2582531 TI - [The health status of stomatologists based on the Cornell Medical Index questionnaire]. AB - The Cornell Medical Index--CMI was used in a group of 674 stomatologists from the North Moravian region to obtain information on their health status. The control group was formed by 126 health community doctors and factory medical officers from the Olomouc, Sumperk and Prerov districts. The results confirm that stomatologists, a risk group, suffer significantly more from somatic and mental problems, as compared with the control group. PMID- 2582532 TI - [Evaluation of information sources and the effectiveness of health education in the North Bohemian Region, as indicated by knowledge of risk factors for cardiovascular diseases]. AB - In May 1988 in the North Bohemian region an anonymous enquiry was made among a representative group of 3,767 respondents which was focused among others on problems of health education. The respondents consider the most important source of health education in 60.37% a talk with their doctor, in 37.67% television and in 17.67% lectures. Newspaper articles, pamphlets and films are rated roughly equally (cca 5% of the respondents). Posters are negligible as a source of health education. Health education is most appreciated by the oldest age group and least by respondents aged 16-30 years. It is necessary to prefer the most appreciated forms of health education and to seek contents and forms attractive for the youngest group of patients. Part of the enquiry was focused on knowledge of risk factors of cardiovascular diseases. Smoking is considered generally most harmful, less than half know about the harmfulness of stress, few respondents know that diabetes is a risk factor (26.3%). The most frequently incorrectly mentioned factor was alcohol. PMID- 2582533 TI - [Results of a study of breastfeeding by pediatric and health education workers 1983-1987]. AB - The authors investigated the rate of breastfeeding in infants born in February in the CSR in 1983-1987. During this period the rate of breastfeeding increased by 3 4%, in particular during the 3rd, 4th and 5th month. The number of infants not breastfed at all did not change and is 12%. By the third month two-thirds of infants cease to be breastfed and only less than one third are breastfed for more than three months. By the end of the 6th month less than one tenth of infants are breastfed. Recommendations to increase the rate of breastfeeding comprise in addition to provisions in obstetric departments (rooming-in) more intense individual health education of mothers in these departments and in paediatric health communities, group training of pregnant women, inclusion of the importance of breastfeeding into syllabi in schools and propagation of breastfeeding in mass media and social organizations of the National Front. PMID- 2582534 TI - [Polyvalency of drugs and its importance in utilization analysis]. AB - In general, morbidity is considered the primary factor in the consumption of drugs. The relationship between the treated nosological unit and the consumption of a given drug for its therapy is, however, not unequivocal and this complicates the quantification of the influence of morbidity on the consumption of drugs. This property of drugs is called in the submitted paper polyvalency or ambivalency. The authors maintain that this property of drugs is reflected also in their consumption. To express this relationship the authors use the mediated response on morbidity treated in ambulatory departments. The polyvalency of drugs is related with the subject's behaviour during therapeutic decisions which determine the final consumption of drugs. PMID- 2582535 TI - [Problems in drug prescriptions. II. The structure of prescriptions from an economic viewpoint]. AB - Based on frequency analysis of 62,209 medical prescriptions from 1985, the authors assessed the structure of the prescription of drugs issued on medical prescription (HVLP, IPL) and their financial value. The mean value of all drugs on one recipe is 37.54 Kcs. Drugs of the IPL group account for 13.3% of the total prescription and 3.9% of the financial value. PMID- 2582536 TI - [Evaluation of factors affecting work disability in health personnel]. AB - The authors assessed and analysed factors responsible for the work incapacity and its duration in health workers. Statistical computing revealed a significantly longer work incapacity in workers suffering from diseases with a severe course. Work incapacity is adversely influenced also by poor living, working and social conditions. Institutes of national health can improve the situation by improving the position of their workers as regards the working, financial, social and health aspect. PMID- 2582537 TI - [Responsibility for damage associated with therapeutic care]. AB - Czechoslovak law ensures in a comprehensive way justified demands of patients for damages caused in conjunction with therapeutic care. As compared with legal regulations in other countries, there is an apparent humanitarian character of the legal responsibility of health institutions. PMID- 2582538 TI - [Specialization training in social medicine and the organization of health care]. AB - During the last five years the Chair of Social Medicine and Organization of the Health Services began to make greater demands also on the stage of training in the specialty which precedes admission to a course in the specialty of social medicine and the organization of health services. The training last three years incl. the participation in a pre-attestation course. The prerequisite of a high standard of training which begins by admitting the student to the discipline is early selection of a tutor (leading worker, specialist in the discipline of social medicine and the organization of health services). The tutor helps with the preparation of a programme of studies which should ensure high standard selfhanded studies and preparation of the new candidate before admission to the course as well as during periods between different sessions which are part of the courses held in the Institute for Postgraduate Medical and Pharmaceutical Training. The investigation made in participants of three consecutive specialization courses should elucidate the present position and stimulate leading workers in the discipline of social medicine and the organization of health services to devote more attention to the selection of subjects admitted to the discipline and to make much greater efforts as regards training of workers, a reserve of future leading workers. At the same time the results of the investigation should provide more information to workers of the Ministry of Health and Social Affairs of the CSR on the state of training in the discipline of social medicine and organization of health services and on the training of workers engaged in the discipline as well as those who are starting work in the discipline. PMID- 2582540 TI - Use of host cell reactivation of cisplatin-treated adenovirus 5 in human cell lines to detect repair of drug-treated DNA. AB - This study demonstrates that whilst some DNA-repair deficiencies can be detected using host cell reactivation of cisplatin (CDDP)-treated adenovirus (Ad5), not all repair deficiencies affected replication of CDDP-treated Ad5 in human cells. A line of fibroblasts (XP25), derived from a patient with a UV-hypersensitive syndrome xeroderma pigmentosum (XP), was found, as previously reported [1], to be deficient in reactivating the treated virus when compared to the apparently repair-proficient human tumor cell lines established from bladder and ovarian carcinomas. However, a testicular teratoma cell line (SuSa), shown previously to be deficient in the repair of guanine-guanine (G-G) intrastrand crosslinks, adenine-guanine (A-G) intrastrand crosslinks and interstrand crosslinks [2], was found to reactivate the treated virus to a similar extent as the repair proficient ovarian tumor cell line and the similarly repair-proficient RT112 cell line derived from a bladder carcinoma. Therefore, not all repair-deficient cell lines were deficient at CDDP-treated Ad5 reactivation. However, the HCR technique may still prove to be useful as a rapid screen for DNA-repair deficiencies in CDDP-sensitive cells of unknown repair capacity. A CDDP-sensitive ovarian tumor cell line (TR175) was deficient in reactivating CDDP-treated Ad5, whilst another ovarian cell line (TR170) of intermediate CDDP sensitivity reactivated the virus to a marginally higher extent than the other more CDDP-resistant repair proficient ovarian cell line (SKOV3). In addition, sublines of either the SuSa cells or the RT112 cells expressing approximately two-fold levels of resistance or increased sensitivity to CDDP, showed no change in their abilities to reactivate this CDDP-treated virus, compared to their parental lines. CDDP treated Ad5 was also used as a lethal probe to obtain cell lines specifically deficient in DNA repair. One such deficient line (SKOV3-C3A), derived from the SKOV3 ovarian carcinoma cell line, displayed an unusual biphasic curve for reactivation of the CDDP-treated virus. Further cell lines derived in this novel manner may prove useful in analysing the genetics of CDDP-repair. PMID- 2582539 TI - Biotransformation of terodiline. V. Stereoselectivity in hydroxylation by human liver microsomes. AB - The stereoselective hydroxylation of N-tert-butyl-4,4-diphenyl-2-butylamine (Terodiline) was studied in human liver microsomes. Formation of the two main metabolites, N-tert-butyl-4(4-hydroxyphenyl)-4-phenyl-2-butylamine (II) and N-(2 hydroxymethyl-2-propyl)-4,4-diphenyl-2-butylamine (VI), was found to be stereoselective. R-Terodiline was preferentially transformed by phenolic hydroxylation to the 2R,4S-II and 2R,4R-II forms with a pronounced selectivity for the former. The formation rate ratio 2R,4S-II/2R,4R-II was about 6, obtained from two liver preparations. S-Terodiline was mainly hydroxylated to the alcohol 2S-VI although phenolic hydroxylation to the 2S,4S-II and 2S,4R-II also occurred, yielding about equal amounts of the two phenols. PMID- 2582541 TI - Irreversible inhibition of rat hepatic glutathione S-transferase isoenzymes by a series of structurally related quinones. AB - The effect of several structurally related 1,4-benzoquinones (BQ) and 1,4 naphthoquinones (NQ) on the activity of rat hepatic glutathione S-transferases (GST) was studied. For the 1,4-benzoquinones, the extent of inhibition increased with an increasing number of halogen substituents. Neither the type of halogen nor the position of chlorine-atoms was of major importance. Similarly, 2,3 dichloro-NQ demonstrated a considerably higher inhibitory activity than 5-hydroxy NQ. 2-Methyl derivatives of NQ did not inhibit GST activity at all. The irreversible nature of the inhibition was shown both by the time-course of the inhibition as well as by the fact that removal of the inhibitor by ultrafiltration did not restore the enzymatic activity. Incubation of quinones and enzyme in the presence of the competitive inhibitor S-hexyl-glutathione, slowed the inhibition considerably, indicating an involvement of the active site. Isoenzyme 3-3 was found to be most sensitive towards the whole series of inhibitors, whereas the activity of isoenzyme 2-2 was least affected in all cases. The inhibition by quinones is probably mainly due to covalent modification of a specific cysteine residue in or near the active site. The differential sensitivities of individual isoenzymes indicates that this residue is more accessible and/or easier modified in isoenzyme 3-3 than in any of the other isoenzymes tested. The findings suggest that quinones form a class of compounds from which a selective in vivo inhibitor of the GST might be developed. PMID- 2582542 TI - Metabolism of 3-methylcholanthrene in rat liver cytosol. AB - The present study investigates the metabolism of the potent carcinogen 3 methylcholanthrene in rat liver cytosol preparations. Three metabolites of 3 methylcholanthrene were characterized by HPLC and GC/MS analysis. These metabolites were identified as 1-hydroxy-3-methylcholanthrene, 1-keto-3 methylcholanthrene and cholanthrene. The results of the present study, taken together with earlier studies, suggests that the first step in the metabolic activation of 3-methylcholanthrene is hydroxylation at the 1-position, the most easily oxidized reactive center in the molecule. PMID- 2582543 TI - Stereoselective glutathione conjugation of a uricosuric diuretic. AB - A reduction of cellular glutathione (GSH) content was observed when isolated rat hepatocytes were incubated with a stereoisomer of a uricosuric diuretic (S-8666) at a high concentration. Subsequent studies have revealed it was due to conjugation of GSH and S-8666 (-)-enantiomer in the liver cytosol. The (+) enantiomer strongly inhibited the conjugation reaction, therefore, GSH depletion did not take place when a racemic form of S-8666 was incubated with the liver cells. A possible chemical structure of the GSH-conjugate is tentatively proposed. PMID- 2582544 TI - [Human pituitary growth hormone cell adenomas, ultrastructural and immunoelectron microscopical study]. AB - 24 cases of growth hormone(GH)-producing pituitary adenomas were studied with electron microscopy and immunoelectron microscopy by protein A-gold complex, 6 cases were identified as densely granulated GH adenoma and 15 cases as sparsely granulated GH adenoma, among which 4 cases were proved by immunoelectron microscopy to be containing granules with prolactin(PRL) activity simultaneously. Intracytoplasmic fibrous bodies were often seen in the sparsely granulated cells anyhow, not all those cells with fibrous bodies possess the secretory granules with GH activity, and fibrous bodies were also detected in some PRL cells of certain mixed type adenoma. This suggests that fibrous bodies might not be the specific morphological feature of pituitary growth hormone cell adenomas. PMID- 2582546 TI - [Experimental study on farmer's lung-like lesions caused by Beauveria bassiana]. AB - 113 lung specimens from rats and mice were observed under both LM and TEM, after inhalation of gonidiospores of Beauveria bassiana for 18 months 78.8% of the 113 cases developed chronic interstitial pneumonia (IP). There were desquamative pneumonitis mainly with macrophage; granuloma with multinucleate giant cells or fibrosis, and localized pulmonary edema. These lesions were firstly described to be caused by the spores here. It was considered that IF lesions might be related to types III, IV hypersensitivity reaction. The authors emphasized that these lesions might be similar to those observed in farmer's lung or extrinsic allergic alveolitis (EAA). PMID- 2582545 TI - [Study of experimental lung lesions caused by extracellular enzyme of Streptomyces thermohygroscopicus]. AB - Rabbits and rats were infected intratracheally with extracellular enzyme of streptomyces thermohygroscopicus (H9-4) for only one exposure and lesions of lung developed which included mononuclear macrophage infiltration as well as bronchitis and vasculitis. The obvious damages in type I pneumocytes, endothelial cells of capillaries and arterioles in the lung were observed by electron microscopy. Immunofluorecent histochemistry examination revealed exudation of plasma fibronectin which might be important to play certein role during the process of wound repairing in lung. The experiment also confirmed that extracellular enzyme of streptomyces thermohygroscopicus might directly damage the lung tissue, and these experimental data may serve valuable reference for studying the etiology and pathogenesis of farmer's lung diseases. PMID- 2582547 TI - [A morphologic and follow-up study on nasopharyngeal lymphoid hyperplasia and its relation to cancer]. AB - Forty-three cases of nasopharyngeal lymphoid hyperplasia (NPLH) were studied morphologically and had been followed-up for a period of 7.5 years in a high incidence city of nasopharyngeal carcinoma (NPC). The authors suggest that NPLH might be recognized as a disease entity in adults. Basing on the sites and gross appearances of the hyperplastic lymphoid tissue, two types of NPLH, namely, adenoids and nodular might be distinguished. The histopathological changes of NPLH are described in detail and its relation to the development of NPC is discussed. According to the data of this study, the authors' opinion is that NPLH is not a precancerous condition. PMID- 2582548 TI - [Histologic and ultrastructural changes in the liver in ageing rats and the effects due to food restriction and noise]. AB - Histologic and ultrastructural changes of the liver in old and non-old Wistar rats and the effects due to persistent restriction of food and exposure to noise were studied. There was increase of hepatocytes with enlarged or double nuclei, and apoptosis as well as fatty change of the liver in the old rats. The incidence of apoptosis and fatty change was lower in those rats with persistent food restriction, but no significant change of the liver was seen in those animals persistently exposed to noisy, environment. PMID- 2582549 TI - [Mucin histochemical changes in various colo-rectal polyps in relation to carcinoma of the large bowel]. AB - 210 various colo-rectal polyps including 46 inflammatory polyps, 21 juvenile polyps, 9 hyperplastic polyps, 65 tubular adenomas, 51 familial polyps, 11 villous adenomas, 7 adenomatous polyps with focal cancer, and 14 carcinoma of the large bowel were investigated by HE,HID-AB,PAT-KOH-PAS staining in order to study the mucin changes of these lesions. N-acetylated and C7,C9 O-acetylated sialomucin were mainly obtained in those adenomas with moderate and severe dysplasia (55-64.3%) and the proportion was even higher in cases of villous adenomas, familial polyps, adenomas with focal cancer and advanced carcinoma. These mucins might be assumed as a criteria in representing malignant transformation. PMID- 2582550 TI - [Fibronectin in gastrointestinal tumors and its relation to biological characteristics of tumor]. AB - Through immunohistochemical technique, distribution of FN in normal mucosa, benign and malignant tumors of human gastrointestinal tract were studied. In normal and adenoma tissues, FN was found in both basement membrane (BN) and interstitial tissue. While in cancer tissue, there was a consistent decrease of BM FN content around the tumor nests particularly more apparently in cases of invading carcinoma. Statistical analysis showed that the reduction of BM FN was correlated with the degree of tumor dedifferentiation but not with the incidence of regional metastases. No association was noticed between the stroma FN and tumor behaviors. Since small blood vessels were usually delineated clearly by the staining for FN, FN might be considered as a marker in identifying the invasion of blood vessel wall by tumor cells. It is suggested that lack of BM FN in tumor tissues might be mainly due to decrease of FN synthesis by the tumor cells. PMID- 2582551 TI - [The influence of castration on the induction of gastric adenocarcinoma by N methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Wistar rats]. AB - Six-week old non-castrated and castrated Wistar rats of both sexes, 20 in each group, received a continuous dose of 83 micrograms/ml MNNG in drinking water for 32 weeks. All animals were autopsied at the 52nd week for pathological examination. The incidence of the gastric adenocarcinoma was 31.6-50.0%, and no significant differences were obtained statistically between different MNNG treated groups. No tumor was found in the control group. Quantitative and qualitative studies of the intramucosal cyst (IC) showed that the ICs might be classified into simple and dysplastic. The former was subdivided into 5 groups and the commonest type was fundic cyst (81%). In MNNG-treated groups, the number of fundic cysts was decreased; nevertheless, the neck cell cysts were increased in number markedly. The number of dysplastic cysts in the MNNG-treated groups was significantly increased and this important precancerous lesion was closely related with the genesis of gastric adenocarcinoma. PMID- 2582552 TI - [Differentiation between primary and metastatic ovarian cancers by monoclonal antibodies specific for gastrointestinal tract carcinomas]. AB - Monoclonal antibodies MG7 and MC3, which are highly specific for gastrocolonic carcinomas, were used in immunohistochemical studies of detecting the relevant antigens present in the primary and metastatic carcinomas in ovaries. All 33 cases of primary ovarian carcinomas examined were negative, and positive reaction was obtained in 94.4% of 18 cases of metastatic carcinomas in ovaries. Results of this investigation confirmed the specificity of MG7 and MC3 in differential diagnosis of primary ovarian cancers from metastatic cancers in ovaries originating from the gastrointestinal tract. PMID- 2582553 TI - [The relationship between DNA content in cervical carcinoma cell and the clinicopathological features]. AB - Nuclear DNA content was determined by flow cytometry in biopsy samples taken from cervical carcinomas of 33 patients. Aneuploid DNA content was found in 24 cases (72.7%). The relationship between DNA content of carcinoma cells and the clinicopathological features was investigated. Carcinomas with aneuploid DNA content were clinically more advanced and histologically poorly differentiated as compared with those with diploid DNA content. DNA content was found neither correlated with the patient's age nor with the growing type of the tumor; and analysis of DNA content by flow cytometry was considered helpful in evaluating tumor malignancy, efficacy of treatment and prognosis. PMID- 2582554 TI - [The significance of mummy cell in the diagnosis of Hodgkin's disease]. AB - The mummy cell is a necrotic single cell in lympho-reticular lesion, and it is characterized by the pattern of distributing isolated in a lympho-reticular background without detachment from the surrounding cells, staining deeply or amphibic in mature both nuclei and cytoplasm and the ghost nuclei are often recognized. Totally, 95 lympho-node biopsies were reviewed, the mummy cells can be found in 21/24 of Hodgkin's disease and 18/71 of other lesions (NHL, reactive hyperplasia etc.). They are more common in nodular sclerosis (NS) and lymphocyte depletion (LD) among the four subtypes of Hodgkin's disease. It is worthwhile to note the suggestive role of mummy cells in pathological diagnosis of Hodgkin's disease. PMID- 2582556 TI - [Malignant histiocytosis and immunodeficiency]. AB - Phenotypes of the tumor cells of malignant histiocytosis (MH) were studied by using monoclonal and polyclonal antibodies in 18 autopsy cases. The tumor cells expressed different antigens in various degrees. Almost all tumor cells showed positive reaction for alpha 1-ACT; partially for alpha 1-AT, LCA and a few for lysozyme as well as LeuM1. It was most likely that the tumor cells of MH originated from the mononuclear phagocytic system (MPS). In order to reveal the relationship between MH and immunodeficiency, morphological changes of the lympho reticular system in 18 cases of MH were studied. It was found that the lymphoid tissues, including lymph nodes, thymus, tonsil, spleen, bone marrow, lymphoid tissues of GI tract and lung etc showed severe depletion. These findings indicate that MH usually combine with immunodeficiency which is also closely related to the pathogenesis and pathological changes of MH. PMID- 2582555 TI - [Pathologic changes of infections in patients after receiving immunosuppressive therapy in renal allografts]. AB - 30 cases of autopsies of patients who died after human renal allografts were studied. The incidence of infection was 60% and the lethal infectious complications amounted to 43%. The most common infectious agents were bacteria, including mycobacterium tuberculosis. In addition, some opportunistic agents, such as Cryptococcus, Aspergillus, mucormycosis, Pneumocystis carinii and cytomegalovirus were also found. All these patients had a history of receiving large dosage of immunosuppressive drugs such as cyclophosphamide, azathioprine, prednisone and dexamethasone after renal allografts. Pathological changes showed marked atrophy of lymphoid tissue and it was compatible with the histologic appearance of immunodeficiency. It is concluded that overuse of immunosuppressive drugs impairs the function of the immune system causing acquired immunodeficiency. Pathological features of lesions caused by the aforementioned infectious agents are also described in this paper. PMID- 2582557 TI - [The relationships between thymus, other immune organs and various diseases in children (analysis of 621 cases)]. AB - Thymuses, spleens, lymph nodes, tonsils and appendices from 621 autopsy cases were reviewed. The degree of atrophy of these organs might be classified into 3 grades. The main diagnoses of these cases involved more than 130 different diseases, which could be divided into 9 groups: infection, benign tumor, malignant tumor, deformity, amniotic fluid aspiration, fungal infection, autoimmune disease and hemorrhage, etc. Cases of infection with a course less than 5 days showed mild atrophy of the thymus and those cases with a longer course might show moderate or severe degree of atrophy. Cases of benign tumor showed no relationship between the degree of atrophy and the course of the disease. Nevertheless, in cases of malignant neoplasms even there was a history of short course, showed severe atrophy of the thymus. Only mild atrophy was obtained in those patients with deformity, amniotic fluid aspiration and hemorrhage, while severe atrophy was seen in those cases with fungal infection and autoimmune disease. In 81% of the cases, the degree of thymus atrophy was in accordance with those of the other immune organs. PMID- 2582558 TI - [An immunohistochemical study of human atherosclerotic lesion]. AB - Cellular composition of 31 cases of human atherosclerotic lesion was studied by immunohistochemical technique. Specimens were taken from the thoracic and abdominal aortas of necrosis. Four monoclonal antibodies were used to identify cell types. Monocytes/macrophages reacting with anti-Leu-M1 or anti-alpha-1-ACT were found in early lesions and some activated areas such as the peripheral region of bottom of atheromatous plagues of the advanced lesions. Some foamy cells also showed positive to alpha-1-ACT. In addition T lymphocytes reacting with anti-UCHL-1 were detected in the early lesions and some activated areas of advanced plaques, and both types of cells were more common in the early than in the advanced lesions. Other types of leukocytes were scanty in both early and advanced atheromatous lesions. In conclusion, the presence of a variable number of monocytes/macrophages and T lymphocytes in human atherosclerotic lesion may represent a cell-mediated immune response which may be very important in the initiation and progression of atherosclerotic lesion. PMID- 2582559 TI - Failed intubation in the parturient. PMID- 2582560 TI - Failed intubation in the parturient. PMID- 2582561 TI - The efficacy of three different methods of transtracheal ventilation. AB - The ability of three different techniques of transtracheal ventilation to reverse hypoxia and provide pulmonary ventilation were examined. Five swine were anaesthetized with isoflurane in oxygen, their tracheas were intubated, and their lungs mechanically ventilated to produce a PaCO2 of 35-40 mmHg. A 14-gauge catheter was inserted percutaneously into the trachea caudad to the tip of the tracheal tube. The animals were then left apnoeic until their oxygen saturation fell to 60 per cent. At this point, attempts were made to ventilate and oxygenate the animals through the tracheal catheter with one of three systems (Jet--50 psi [2585 mmHg] driving pressure controlled with a thumb operated valve, Flush-fresh gas outlet of an anaesthetic machine with flow controlled by the flush button, or Circle--standard anaesthesia circle system with pressures greater than 60 mmHg). Arterial blood gas determinations were made every minute for five minutes after beginning transtracheal ventilation. Both the Jet and Flush modes resulted in a mean PaO2 greater than 250 mmHg within one minute of their initiation whereas the PaO2 with the Circle system never exceeded 180 mmHg even at five minutes. The Flush and Jet modes produced a decrease in the PaCO2 (from 80 mmHg to 35-45 mmHg) over the five minutes. In contrast, it was not possible to provide adequate ventilation with the Circle system as evidence by an increasing PaCO2 (from 80 mmHg to less than 110 mmHg at five minutes).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582562 TI - Epidural morphine reduces halothane MAC in the dog. AB - Morphine, 0.1 mg.kg-1 was administered epidurally on two different occasions to ten dogs to determine the effect of two different volumes of saline dilution, 0.13 and 0.26 ml.kg-1, on the minimum alveolar concentration (MAC) of halothane as determined by subcutaneous electrical current applied to the fore and hind limbs in a random order. Following MAC determination with halothane alone, epidural morphine was administered and MAC was redetermined. Epidural morphine significantly reduced, P less than 0.001, the MAC of halothane for fore and hind legs in both volume groups; from 1.04 +/- 0.038 to 0.68 +/- 0.034 and 0.60 +/- 0.017 for for and hind limbs, respectively, in the large volume group, and from 0.96 +/- 0.038 to 0.66 +/- 0.088 and 0.60 +/- 0.030 for fore and hind limbs, respectively, in the small volume group. The reduction in MAC was significantly greater, P less than 0.025, in the hind limb. This study indicates that epidural morphine reduces the halothane requirements in the dog in a segmental manner. The volume of administration was not shown to be critical. Epidural morphine, 0.1 mg.kg-1, diluted in 0.13 to 0.26 ml.kg-1 saline produces significant analgesia in the dog as far forward as the fore limb and will reduce the halothane requirement to permit surgery. PMID- 2582563 TI - Visual evoked potentials during thiopentone-fentanyl-nitrous oxide anaesthesia in humans. AB - Visual evoked potentials (VEP) during thiopentone-fentanyl-nitrous oxide anaesthesia were studied in 15 healthy patients undergoing non-neurosurgical procedures. The VEP was recorded before and at 1 and 2 min after induction of anaesthesia with 5-6 mg.kg-1 of thiopentone. After recording the 1 and 2 min VEPs, anaesthesia was maintained with a fentanyl-nitrous oxide-oxygen combination, and further recordings were made at 5, 10, 15 and 20 min after induction. The 1 and 2 min VEPs showed a marked decrease in the amplitudes. Latencies were increased. The amplitudes gradually returned to the control level at 15 min, while the latencies remained increased throughout the study period. In conclusion, thiopentone should be avoided during the critical period of VEP recording. Once it is given, at least 15 min should elapse before an appropriate interpretation of the VEP can be made. Thiopentone-fentanyl-nitrous oxide anaesthesia slightly increases the latencies of the VEP. These effects should be considered in the interpretation of the VEP when thiopentone-fentanyl-nitrous oxide anaesthesia is used. PMID- 2582564 TI - Rectal pH in children. AB - In an attempt to establish normal values for rectal pH in children, we have measured pH in 100 paediatric patients. Measurement of rectal pH was performed in 25 infants and 75 children (27 girls and 73 boys) using a monocrystalline antimony electrode. Rectal pH was 9.6 +/- 0.9 (mean +/- SD, range 7.2 to 12.1) and was independent of sex, age and nutrition. This wide range of rectal pH values offers a possible explanation for the widely scattered bioavailability of drugs administered by the rectal route. Mean rectal pH was considerably higher than that reported for adults; this unexpected alkalinity should be taken into account, when drug formulations are considered for rectal administration in children. PMID- 2582565 TI - Anaesthetic management of emergency caesarean section followed by pulmonary embolectomy. AB - This report discusses the anaesthetic management of a patient undergoing emergency Caesarean section followed by an open pulmonary embolectomy with cardiopulmonary bypass. This case was complicated by the major physiological alterations associated with pregnancy and delivery, massive blood loss, cardiac dysrhythmias, hypotension, and cardiac arrest. Both patients, mother and child, made a full recovery. PMID- 2582566 TI - Obstetric epidural anaesthesia in patients with Harrington instrumentation. AB - This five-year retrospective study reviews our experience with epidural obstetric analgesia in patients with previous Harrington rod instrumentation (HRI) for correction of idiopathic scoliosis. Patients were identified by the presence of an antepartum anaesthetic consultation for HRI. The anaesthetic record was examined to determine the frequency of epidural catheter insertion and any problems related to this procedure. Nine epidural insertions were attempted in the 16 patients identified. Five were uncomplicated but four were complicated by one or more of: failure to identify the epidural space, blood vessel trauma, dural puncture, failure to obtain analgesia or the need for multiple attempts before successful insertion. There were no sequelae related to epidural insertion. There were no sequelae related to epidural insertion. We conclude that patients with HRI may be offered epidural anaesthesia for labour and delivery provided that they are informed of the increased risk of complications. PMID- 2582567 TI - Computerized axial tomo-epidurographic and radiographic documentation of unilateral epidural analgesia. AB - A 23-year-old primigravid patient who received epidural analgesia for pain of labour presented with persistent, apparently irremediable, unilateral analgesia. Computerized axial tomo-epidurography demonstrated absence of circumferential spread due to lateral placement of the catheter. Transforaminal escape of contrast medium into the paravertebral area had occurred and anterior and posterior midline partitioning of the epidural space was obvious. All the usual measures to promote contralateral analgesia, except re-insertion of the catheter, had been tried without success. PMID- 2582568 TI - Epidural anaesthesia for caesarean section in patients with active recurrent genital herpes simplex infections: a retrospective review. AB - The safety of epidural anaesthesia in patients with active, recurrent genital herpes simplex (HSV) infections is controversial. We reviewed the six-year experience of the use of epidural anaesthesia in this patient population in two institutions. Eighty-nine parturients with active genital HSV were administered epidural anaesthesia for Caesarean section. No patient suffered an adverse outcome related to either the anaesthetic or the virus. The theoretical risks of regional anaesthesia in the parturient with active herpes genitalis are reviewed. We conclude from available data that the risk of an adverse outcome is small and does not contraindicate the use of epidural anaesthesia in patients with recurrent infection. PMID- 2582569 TI - Postpartum headache following regional analgesia; a symptom of cerebral venous thrombosis. AB - In this report we describe a patient who developed severe headache following uneventful continuous epidural analgesia for labour and delivery. Initially it was thought that she had a spinal headache. However, with the aid of Magnetic Resonance Imaging the diagnosis of cerebral venous thrombosis was later established. The entity of cerebral venous thrombosis, its manifestation, pathology, diagnosis and treatment are discussed. PMID- 2582570 TI - [Accidental catheterization of the subdural space: a complication of continuous spinal anesthesia and continuous peridural anesthesia]. AB - Two cases of subdural catheter placement following continuous spinal and continuous epidural anaesthesia are presented. In the first, despite an easy reflux of clear cerebrospinal fluid through the catheter, the injection of 4 ml bupivacaine 0.5 per cent with epinephrine 1:200,000 followed by 3 ml tetracaine 0.5 per cent showed a failure of spinal anesthesia. In the second, the administration through the catheter of 20 ml lidocaine 2.0 per cent CO2 plus epinephrine 1:200,000 and of ten ml bupivacaine 0.5 per cent lead to an insufficient, patchy and asymmetrical analgesia. The clinical signs observed in these two cases are compared with previous publications. The importance of an x ray contrast study to confirm the diagnosis of subdural catheter insertion is stressed. PMID- 2582572 TI - A simple device for monitoring neuromuscular blockade in children. AB - A simple instrument for measuring adductor pollicis tension in children has been devised. The thumb sensor utilizes a thin conical rubber seal obtained from a 5, 10 or 20 ml Becton Dickinson syringe. A syringe barrel of similar size, fixed at right angles to the sensor, forms a handle for the fist. The sensor is linked to a pressure transducer with non-compliant tubing. Pressure output of the saline filled system was found to be linearly related to the force exerted on each size of the sensor. In 20 children, aged two to eight years, the device, fitted in turn with the 5, 10 and 20 ml syringe seal sensors, gave train-of-four (TOF) ratios which showed close correlation (coefficient r = 0.96, 0.93, 0.95) and agreement (regression slope b = 0.97, 0.95, 0.98) with those of a force transducer. Thus, inspection of the displayed TOF pressure pulses gives a rapid and reliable estimate of neuromuscular blockade. PMID- 2582571 TI - Successful treatment of chronic pancreatitis pain with interpleural analgesia. AB - Interpleural analgesia has recently been shown to be effective in the management of various chronic pain syndromes. We have used interpleural analgesia successfully in 11 patients with severe chronic pancreatitis of 24-38 months' duration. Daily injections of 30 ml of 0.5 per cent bupivacaine with epinephrine 5 mu.ml-1, were given through a percutaneously inserted pleural catheter over a five- to ten-day period. Patients have remained pain-free during follow up which ranges from 24 to 40 weeks. This method of providing analgesia for the patient suffering from the pain of chronic pancreatitis is simple, safe, effective and can be provided on an outpatient basis. PMID- 2582573 TI - Computerized schedules--one solution to variable workstyles. AB - A computerized scheduling program was developed to provide hospital anaesthetic coverage and yet still satisfy the complex workstyles of 30 anaesthetists. Hospital commitments required ten anaesthetists available each weekday and four each weekend day for after-hours coverage of the intensive care units and operating rooms. The workstyles included part-time arrangements, limited calls by some individuals, and calls restricted to certain anaesthetists with specific areas of expertise. Rules were defined to limit the proximity of late calls to avoid fatigue and computer software was developed. For each scheduling period, the program assists in making daily call assignments based on each anaesthetist's availability and a priority ranking system. It is flexible enough to allow personal preferences. The number and distribution of all calls scheduled are counted. When the assignments are completed, differences are reconciled. For two years, this program has proved superior to previous manual systems for scheduling this group of anaesthetists with variable workstyles. PMID- 2582574 TI - Respiratory depression and spinal opioids. PMID- 2582575 TI - Metoclopramide inhibits plasma cholinesterase. PMID- 2582576 TI - Contamination of syringes. PMID- 2582577 TI - A portable anaesthetic monitoring trolley for labour room placement of epidurals. PMID- 2582579 TI - Another cause of tracheal tube failure. PMID- 2582578 TI - Transfusion-related 2-to-1 electromechanical block during surgery. PMID- 2582580 TI - Avoiding unintentional arterial cannulation. PMID- 2582581 TI - Different mechanisms may mediate anaesthesia and analgesia. PMID- 2582582 TI - Characterization of hemodynamic, hematologic, and biochemical responses to administration of liposome-encapsulated hemoglobin in the conscious, freely moving rat. AB - To improve the outcome of trauma victims and of patients undergoing high-blood loss surgical procedures and to avoid the many serious complications of blood transfusion, there is a need for an oxygen-carrying blood substitute. Synthetic erythrocytes composed of liposome-encapsulated hemoglobin (LEH) represent one of the significant research efforts in this direction. The purpose of the present study was to examine some of the cardiovascular, hematologic, and biochemical effects of a recently developed LEH preparation in the conscious rat (n = 7). LEH increased mean arterial pressure (MAP) by +18.7 +/- 4.7 mm Hg (P less than 0.01) and heart rate (HR) by +117 +/- 18 beats/min (P less than 0.05). Platelet count dropped to 40% of basal value (P less than 0.01), while plasma thromboxane B2 (TXB2) increased by +25.1 +/- 5.4 pg/100 microliters (P less than 0.001). There was no effect on plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Hemoglobin and hematocrit levels were elevated as well as the white blood cell count [( WBC] lymphocytosis). The platelet and TXB2 responses to LEH showed negative correlation (R = -0.56, P less than 0.01). The injection of the liposome vehicle (LIP) decreased MAP by -16.5 +/- 5.1 mm Hg (P less than 0.01) and platelets, but increased HR, WBC, and TXB2. All observed effects exerted by LEH and LIP were transient, and basal levels obtained 120 min after LEH injection. These data suggest that while LEH maintains some physicochemical properties of red blood cells, its biological properties at the present time indicate potential cardiovascular and hematological liabilities. Furthermore, it seems that the phospholipid bilayer alone or in combination with free Hb might be responsible for the biological effects of LEH. PMID- 2582583 TI - Changes in anti-endotoxin-IgG antibody and endotoxaemia in three cases of gram negative septic shock. AB - Circulating endotoxin levels and IgG antibodies to a range of Gram-negative bacterial lipopolysaccharides (LPS) (endotoxins) of different sizes and structures were measured daily in three cases of septic shock. There was an inverse relationship between endotoxin levels and cross-reactive antibodies to the core glycolipid (CGL) region of lipopolysaccharide. This suggests that antibody to LPS-CGL was initially consumed by a superabundance of endotoxin, and that a resurgence of intrinsic anti-LPS-CGL antibody levels may be associated with a reduction of circulating endotoxin. The implications of these findings for passive antibody therapy of septic shock are discussed. PMID- 2582584 TI - Pressure-induced vasoconstriction of renal microvessels in normotensive and hypertensive rats. Studies in the isolated perfused hydronephrotic kidney. AB - The capacity of small arteries to respond to increased intravascular pressure may be altered in hypertension. In the kidney, hypertension is associated with a compensatory shift in the autoregulatory response to pressure. To directly determine the effects of established hypertension on the renal microvascular response to changes of perfusion pressure, we evaluated pressure-induced vasoconstriction in hydronephrotic kidneys isolated from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). Vessel diameters of interlobular arteries (ILAs) and afferent and efferent arterioles were determined by computer-assisted videomicroscopy during alterations in renal arterial pressure (RAP) from 80 to 180 mm Hg. Increased RAP induced a pressure-dependent vasoconstriction in preglomerular vessels (afferent arterioles and ILAs), but not in postglomerular vessels (efferent arterioles). The calcium antagonist nifedipine prevented pressure-induced afferent arteriolar vasoconstriction with a similar half-maximal inhibitory concentration (IC50) (WKY, 63 +/- 27 vs. SHR, 60 +/- 32 nM). The pressure-activation curves for ILAs in SHR and WKY were similar. In contrast, the pressure-activation curve for afferent arterioles in SHR kidneys exhibited a rightward shift, which was observed at every segment of the afferent arteriole (i.e., near ILA, at midportion, and near glomerulus). These findings demonstrate that the ILA and the afferent arteriole both possess the ability to constrict in response to increased pressure, whereas this property is lacking in the efferent arteriole. Hypertension was associated with a compensatory shift in the pressure response of the afferent arteriole, such that higher RAPs were required to elicit vasoconstriction in this vessel. PMID- 2582585 TI - Rate-dependent changes in intraventricular conduction produced by procainamide in anesthetized dogs. A quantitative analysis based on the relation between phase 0 inward current and conduction velocity. AB - Antiarrhythmic drug effects on maximal upstroke velocity (Vmax) are frequency dependent, which implies that the effects of these drugs on conduction should also be rate dependent. Previous in vivo studies have been limited by assumptions about unchanging propagation pathway, and by the empirical use of a first-order recovery model. To explore time-dependent antiarrhythmic drug-induced conduction slowing in vivo, we used 56-electrode epicardial mapping in chloralose anesthetized dogs with formalin-induced atrioventricular block. Interval dependent changes in conduction time were assessed under control conditions and then after three loading and maintenance infusions of procainamide. Under control conditions, epicardial activation time (86 +/- 26 msec at a basic cycle length of 300 msec) was unchanged (87 +/- 24 msec) by pauses up to 6.6 +/- 2.2 seconds. Procainamide caused conduction slowing that dissipated as a function of recovery interval, with 94 +/- 6% recovery over a maximum pause of 6.7 +/- 1.5 seconds, but did not alter activation pattern. Drug-induced changes in conduction were evaluated by use of a mathematical model assuming phase 0 inward current proportional to conduction velocity squared. Conduction changes were better fitted by this "quadratic model" (least sum of squared deviations 3.9 x 10(-3) by mapping in five dogs, 2.7 x 10(-2) by use of QRS duration in nine dogs) than by a monoexponential model (sum of squared deviations 5.7 x 10(-3) by mapping, 3.4 x 10(-2) with QRS; p less than 0.01 vs. quadratic model for each). As predicted by theoretical analysis, recovery time constants from the quadratic model were similar to time constants for procainamide-induced changes in Vmax in vitro, and significantly longer than values obtained with a monoexponential model. Drug induced changes in QRS duration were highly correlated with simultaneous changes measured by epicardial mapping (r = 0.95, p less than 0.001), indicating that QRS duration is a valid index of drug effects on ventricular conduction. We concluded that procainamide causes interval-dependent changes in ventricular conduction in vivo that are consistent with a proportional relation between phase 0 inward current and the square of conduction velocity. These observations have important potential implications for the dose-dependent and heart rate-dependent effects of antiarrhythmic drugs. PMID- 2582586 TI - Differences in load dependence of relaxation between the left and right ventricular myocardium as a function of age in rats. AB - To determine whether the variation in the magnitude of work load sustained by the left and right ventricles during adulthood and senescence affects the load dependent aspect of relaxation, posterior papillary muscles from the left and right ventricles of rats at 4, 10, and 20 months of age were studied under variably loaded conditions in vitro. Because of differences between the life spans of Fischer and Sprague-Dawley rats, the functional characteristics of relaxation were investigated to evaluate the possibility of a differential age associated response in these two strains of animals. The kinetic performance of the diastolic phase of myocardial contraction was measured by assessing the relative time during which load bearing occurred in a series of afterloaded isotonic twitches. This measurement was expressed as the ratio of the duration of afterloaded isotonic shortening and relengthening to the time required for isometric force to decline to the same level during isometric relaxation. A ratio of less than unity identified a load-dependent state whereas a value greater than one reflected a load-independent condition. Results showed that the right myocardium was completely load independent whereas the left myocardium was fully load dependent at all physiological afterloads. Aging reduced the load independence of the right ventricle and the load dependence of the left ventricle in Fischer rats. In contrast, no aging effect on the properties of afterloaded isotonic relaxation was seen in Sprague-Dawley rats. In conclusion, distinct differences exist in the mechanical dynamics of inactivation between the left and right ventricular myocardium. Aging reduced these variations in Fischer rats but had no apparent influence in Sprague-Dawley animals up to 20 months after birth. PMID- 2582587 TI - Adenosine produces pulmonary vasoconstriction in sheep. Evidence for thromboxane A2/prostaglandin endoperoxide-receptor activation. AB - Adenosine, an intermediate product in the metabolism of ATP, is thought to produce vasodilation in all vascular beds with the exception of the kidney. Due to its theoretical potential as a pulmonary vasodilator, we studied the hemodynamic effects of adenosine in the pulmonary vasculature of chronically instrumented awake sheep. Adenosine produced significant pulmonary vasoconstriction instead of the expected vasodilatation. Bolus injections of adenosine into the superior vena cava produced a dose-dependent increase in pulmonary artery pressure that was entirely due to an increase in vascular resistance, since cardiac output decreased slightly. This effect is produced via activation of specific cell surface adenosine receptors, since it was blocked by the adenosine-receptor antagonists theophylline and dipropylsulfophenylxanthine. The cell type involved in adenosine-induced pulmonary vasoconstriction appears to be located within the lung, since vasoconstriction was blunted when adenosine was infused into the left atrium, distal to the lung. However, adenosine does not directly vasoconstrict the pulmonary vasculature, because its effect could be completely abolished by cyclooxygenase inhibition with either indomethacin or ibuprofen and by a thromboxane A2/prostaglandin endoperoxide-receptor antagonist (SQ 29,548). Adenosine-induced vasoconstriction was also greatly reduced after inhibition of thromboxane synthesis. Thus, adenosine produced pulmonary vasoconstriction through generation of a thromboxane/endoperoxide product. Whether endogenous adenosine is involved in the generation of pulmonary vasoconstriction seen in pathophysiological states remains to be determined. To our knowledge, this is the first clear evidence for adenosine-induced vasoconstriction outside the kidney and for an interaction between adenosine and eicosanoid mechanisms. PMID- 2582588 TI - Baroreflex control of renal sympathetic nerve activity is preserved in heart failure despite reduced arterial baroreceptor sensitivity. AB - The purpose of this study was to determine if arterial baroreflex control of sympathetic nerve traffic is impaired in heart failure. We recorded renal nerve activity during changes in arterial pressure while simultaneously recording from aortic baroreceptor afferent fibers in 10 dogs with heart failure induced by rapid ventricular pacing and in 10 sham animals. Sensitivity of the aortic baroreceptors (percent change in nerve activity per millimeters mercury change in mean arterial pressure) was reduced in the heart failure group (heart failure, 2.3 +/- 0.3; sham, 3.6 +/- 0.4, p = 0.02). Despite the reduced sensitivity of aortic baroreceptors in heart failure, there was no difference in the baroreflex gain of renal nerve activity (heart failure, -5.5 +/- 1.4; sham, -5.8 +/- 1.3, p = NS). These values tended to decrease in both groups after vagotomy. The relation between baroreceptor input and renal sympathetic output, or central baroreflex gain (percent change in renal nerve activity divided by percent change in aortic nerve activity) was similar in both groups before vagotomy (heart failure, -2.4 +/- 0.6; sham, -2.3 +/- 0.5, p = NS). Vagotomy reduced central gain in the sham group (-0.9 +/- 0.1, p = 0.03) but not in the heart failure group ( 1.7 +/- 0.5, p = NS), suggesting that the contribution of vagal afferents in the baroreflex arc is reduced in heart failure. Baroreflex control of R-R interval was attenuated in heart failure when assessed by blood pressure elevation but not reduction, indicating abnormal parasympathetic but preserved cardiac sympathetic mechanisms in heart failure. Thus, dogs with heart failure exhibit reduced sensitivity of aortic baroreceptors but preserved baroreflex control of renal nerve activity. Reduced baroreceptor sensitivity with preservation of baroreflex control of sympathetic nerve activity may contribute to the sympathoexcitatory state known to exist in heart failure. PMID- 2582589 TI - Inhibition of cardiac vagal effects by neurally released and exogenous neuropeptide Y. AB - Neuropeptide Y (NPY) attenuates vagal effects on cardiac cycle length, presumably by inhibiting the release of acetylcholine from vagal nerve endings. We sought to determine if NPY inhibited the vagal effects on atrioventricular (AV) interval and atrial contraction in a manner similar to its inhibition of the vagal effects on cycle length. In 19 anesthetized dogs we measured the vagal effects on cycle length, AV interval, and atrial contraction before and after 3-minute trains of sympathetic stimulation or before and after exogenous NPY (20 micrograms/kg i.v.). Three minutes after 10-Hz sympathetic stimulation, the vagal effects on cycle length and AV interval were attenuated by 52 +/- 9% and 63 +/- 8%, respectively. Phentolamine significantly augmented this attenuation, but propranolol had no appreciable effect. In the control group of animals or in the group that received phentolamine, the vagal effects on atrial contraction measured before and after sympathetic stimulation were not significantly different. In these two groups, however, the basal atrial contraction was reduced substantially after the cessation of sympathetic stimulation. Propranolol prevented this reduction in atrial contraction. After propranolol, the vagal effects on atrial contraction 3 minutes after sympathetic stimulation were attenuated by 31 +/- 6%. Exogenous NPY had no direct effect on cycle length, AV interval, or atrial contraction, but exogenous NPY did persistently inhibit the vagal effects on each of these cardiac processes. Three minutes after NPY was given, the vagal effects on cycle length, AV interval, and atrial contraction were inhibited by 62 +/- 7%, 69 +/- 5%, and 68 +/- 5%, respectively. We conclude that NPY attenuates the vagal effects on the atrial myocardium and on the sinus and AV nodes. In the absence of beta-blockade, the inhibitory effect of neurally released NPY on the vagally induced decreases in atrial contraction may be masked by the reduction in the atrial contraction that occurs after sympathetic stimulation. PMID- 2582590 TI - Chronotropic responses of chick atria to field stimulation after various neural crest ablations. AB - Three models of altered autonomic innervation of the chick heart have been developed in the last few years. These include sympathetically aneural heart, parasympathetically aneural heart, and heart with cholinergic innervation reconstituted from the nodose placodes. The neural status of these hearts has been assessed by a variety of morphological and biochemical methods, but the functional status of innervation is not known. In the present study, we have used electrocardiography and field stimulation to determine the functional neural status of the three different innervation models. The RR and QTc intervals were measured to assess the dominant autonomic tone and autonomic dysfunction in the heart. Even though the RR and QTc intervals were found to be identical in sham and experimental embryos, field stimulation of superfused atria showed that the sympathetically aneural heart has functional cholinergic innervation but lacks any sympathetic response. Hearts from embryos which were parasympathetically aneural lacked a cholinergic response to field stimulation and were judged to be functionally parasympathetically aneural. Hearts with cholinergic ganglia reconstituted from the nodose placodes have normal RR and QTc intervals as well as a normal cholinergic response to field stimulation. The results indicate that these neurons are functionally indistinguishable from neural crest-derived neurons. PMID- 2582591 TI - Acetylcholine causes coronary vasodilation in dogs and baboons. AB - Intracoronary administration of acetylcholine or efferent vagal stimulation causes coronary vasodilation in dogs. However, in baboons it has been reported that intracoronary acetylcholine results in a fall in coronary blood flow and that stimulation of the vagi is without effect. The dose response of intracoronary acetylcholine and the effect of efferent vagal stimulation on the coronary circulation were reinvestigated in closed-chest, anesthetized dogs and baboons. The left main coronary artery was cannulated and perfused at constant pressure. alpha-Adrenergic and beta-adrenergic receptors were pharmacologically blocked with phenoxybenzamine and propranolol. Heart rate was held constant by right ventricular pacing. In dogs, intracoronary infusion of acetylcholine (1-300 micrograms/min) elicited a dose-dependent increase in steady-state coronary blood flow and coronary sinus oxygen tension, without a change in myocardial oxygen consumption. Vagal stimulation caused a coronary vasodilation that was attenuated by a metabolically mediated decrease in flow. In baboons, acetylcholine increased steady-state coronary blood flow in the dose range of 1-10 micrograms/min, caused little change at 30 micrograms/min, and decreased flow at 100-300 micrograms/min. Coronary sinus oxygen tension increased in a dose-dependent manner up to 10 micrograms/min. Myocardial oxygen consumption was unchanged in the dose range of 1-10 micrograms/min and declined between 30 and 300 micrograms/min. Efferent stimulation of the vagi resulted in coronary dilation obscured by a metabolic reduction of flow. It is concluded that 1) low doses of acetylcholine elicit a primary coronary vasodilation in both species, but in baboons high doses of acetylcholine cause a reduction of both myocardial oxygen consumption and coronary blood flow below control values and 2) vagal stimulation causes a competition between coronary vasodilation and metabolic reduction of flow in dogs and baboons. PMID- 2582592 TI - Multiple regional differences in cellular properties that regulate repolarization and contraction in the right atrium of adult and newborn dogs. AB - Recent studies of isolated cardiac myocytes have generated the need for detailed information about regional electrophysiological differences in the atrium. We measured the spatial distribution of action potentials in adult and newborn canine right atria. Multiple regional differences in action potential shape and duration were found. The multiple regional differences produced an overall simple pattern: the longest action potentials occurred in the area of the sinus node, and the action potential duration decreased with increasing distance from the sinus node area. To account for the overall pattern, we tested factors considered important in causing atrial action potential shape differences (e.g., electronic interactions). None of the factors tested accounted for the regional differences. We then found regional differences in the responses to pauses, which suggested that differences in the properties of individual cells accounted for the regional repolarization differences. If so, genetic regulation of the regional differences may produce the overall pattern on a developmental basis. Experiments in newborn atria showed that only in the upper crista was the spatial pattern similar to that of the adult; there was little variability in action potential shape and duration in the other areas. As a further test for associated regional differences in cell properties, we examined for differences in the isoform expression of troponin T (TnT1, TnT2, TnT3, and TnT4), a protein important in excitation-contraction coupling. In adults, the greatest proportion of TnT1 occurred in the area of the sinus node, and its proportion decreased with increasing distance from the sinus node area in association with a relative increase in the proportion of TnT2. In newborn atria the relative amount of TnT1 was greatest in the upper crista (similar to adult), but little difference was found in the distribution of the isoforms in the other regions. The correspondence between the regional differences in repolarization and in the expression of the troponin T isoforms in adult and newborn atria suggests that 1) cellular ionic mechanisms vary regionally to coordinate differences in action potential configuration with differences in cell properties that regulate contractility and 2) genetic expression of the systems that regulate repolarization and mechanical cellular properties are under similar developmental and regional control. PMID- 2582593 TI - Interaction of inhomogeneities of repolarization with anisotropic propagation in dog atria. A mechanism for both preventing and initiating reentry. AB - Having found the regional differences in right atrial action potentials shown in an accompanying article, we tested two seemingly paradoxical hypotheses: 1) The spatial pattern of repolarization provides a protective mechanism against reentry, and 2) repolarization inhomogeneities interact with anisotropic discontinuous propagation to produce reentry. Measurement of multidimensional refractory periods demonstrated an anisotropic distribution within large bundles with the longest refractory periods in the medial upper crista terminalis (sinus node area), a distribution similar to that of action potential durations. Also, discontinuities of repolarization were found at muscle bundle junctions. Early premature impulses originating in the sinus node area propagated throughout the right atrial preparations without conduction disturbances or reentry. Conversely, early premature impulses that originated at sites distal to the sinus node area resulted in localized conduction block at multiple sites, which frequently produced complex conduction changes and reentry. The critical nature of the site of origin of a premature impulse in initiating reentry was related to locations where the steepest repolarization gradients occurred: within anisotropic bundles in the direction of highest axial resistance (across fibers) and at muscle bundle junctions that represented localized discontinuities of axial resistance. The multiple conduction abnormalities at localized sites interacted to produce different types of reentry at a larger size scale (25 mm2 to several cm2). In each case, neither repolarization inhomogeneities (leading circle concept) nor anisotropic discontinuous propagation was the only "mechanism" involved. That is, reentry at a macroscopic size scale occurred as a result of a combined repolarization-anisotropic discontinuous propagation mechanism. PMID- 2582594 TI - Alterations in collagen cross-linking impair myocardial contractility in the mouse heart. AB - A number of genetic disorders in humans are associated with defects in the synthesis and metabolism of collagen, which are accompanied by multiple cardiovascular disease processes. To determine whether genetically determined cross-linking abnormalities of collagen may alter cardiac function, left ventricular papillary muscles of mice with a genetic defect in the cross-linking of collagen (Movbr) were studied in vitro. With respect to controls, increases in time to peak tension, from 102 +/- 1.4 to 125 +/- 5.4 msec (p less than 0.001), and time to one-half relaxation, from 76 +/- 3.0 to 98 +/- 6.1 msec (p less than 0.05), were measured. Moreover, resting tension at the length associated with maximum developed isometric force (L) was elevated, from 11.1 +/- 1.7 to 19.3 +/- 1.1 mN/mm2 (p less than 0.001), and a similar difference was also seen throughout the physiological range of muscle lengths. In contrast, developed tension was depressed at 93-97% of L. Peak rate of tension rise and decay were diminished whereas time to peak rate of tension rise was prolonged. Isotonically, a decrease in the magnitude of peak shortening at L, from 4.0 +/- 0.5 to 2.0 +/- 0.2% (p less than 0.04), and an increase in time to peak shortening, from 100 +/- 2.3 to 129 +/- 2.8 msec (p less than 0.001), were seen. In addition, peak velocities of shortening and relengthening were diminished in the Movbr mouse heart. In conclusion, the impairment in collagen cross-linking alters cardiac mechanics by a reduction in force-generating ability and a prolongation of the timing parameters of the systolic and diastolic phases of contraction in vitro. PMID- 2582595 TI - Hemodynamics of the stage 12 to stage 29 chick embryo. AB - The heart is the first functioning organ in the embryo and provides blood flow during cardiac morphogenesis from a muscle-wrapped tube a few cells thick to the four-chambered pump. We described the hemodynamics of the chick embryo from stage 12 (50 hours of a 21-day incubation) to stage 29 (6 days), during which the embryo weight increased 120-fold. We measured ventricular, embryo and extraembryonic vascular bed wet weights, dorsal aortic blood flow with a directional pulsed-Doppler velocity meter, and ventricular and vitelline arterial blood pressures with a servo-null micropressure system. The data are reported as mean +/- SEM. With rapid development and morphogenesis, dorsal aortic blood flow increased from 0.015 +/- 0.004 to 2.40 +/- 0.20 mm3/sec parallel to the geometric increase of wet embryo weight from 2.22 +/- 0.10 to 267.5 +/- 9.7 mg. Dorsal aortic blood flow normalized for embryo and extraembryonic weight remained relatively constant (Y = 2.13 + 0.02X, r = 0.23, SEE = 0.03). Stroke volume increased from 0.01 +/- 0.003 to 0.69 +/- 0.03 mm3, and heart rate doubled from 103 +/- 2 to 208 +/- 5 beats/min. Systolic, diastolic, and mean vitelline arterial pressure increased linearly from 0.32 +/- 0.01, 0.23 +/- 0.01, and 0.28 +/- 0.01 mm Hg at stage 12 to 2.00 +/- 0.06, 1.22 +/- 0.03, and 1.51 +/- 0.04 mm Hg, respectively, at stage 29. Ventricular peak systolic and end-diastolic pressure increased from 0.95 +/- 0.04 and 0.24 +/- 0.02 at stage 12 to 3.45 +/- 0.10 and 0.82 +/- 0.03 at stage 29, respectively. The hemodynamic waveforms were similar to those found in the four-chamber heart of the mature animal. These data are integral to understanding the interrelation of function and form during cardiac development. PMID- 2582597 TI - Activation patterns in healed experimental myocardial infarction. AB - The maximum amplitude of vector loops formed by summing orthogonally recorded bipolar electrograms has been shown to reflect the direction of activation in cardiac muscle. To investigate whether components of vector loops could provide information about different activation directions in local areas of myocardium, we correlated "instantaneous vectors" with isochronal activation patterns in an in vitro preparation of experimental myocardial infarction. In thirteen 3 mm x 3 mm regions studied (from 11 tissues), at least 16 microelectrode impalements with a minimum density of 0.8 mm between sites were made. In seven situations in which notched, irregular, and prolonged duration electrograms were present, vector loops pointed in the same general direction throughout their entire time course. In these preparations, microelectrode impalements demonstrated only a single major direction of activation. In five of six areas in which multidirectional vector loops were present, two or more separate local directions of activation corresponded to the directions of the vector loop. Instantaneous vectors were then used to analyze propagation patterns in vivo in 10 animals with 2-4-week-old experimental myocardial infarction. Of 150 sites in the 10 animals, 13% contained more than one major local direction of activation. In 11 markedly abnormal sites, electrograms were recorded during pacing from four sites around the recording probe. When comparing electrogram characteristics from the four sites, a mean difference of 5.9 mV in electrogram amplitude and 19.1 msec in electrogram duration (coefficient of variation, 27% for amplitude and 22% for duration) was found. In only two of the 11 sites was it found that the same number of activation directions occurred from all pacing sites. We conclude: 1) Instantaneous components of vector loops accurately represent local directions of cardiac activation at differing times. 2) Most areas of experimental myocardial infarction have only one major direction of activation despite the presence of abnormal electrograms. 3) In some regions, however, two major local directions of activation can be identified within a relatively local area. 4) Geometric activation patterns in experimental myocardial infarction are markedly dependent on initial activation direction. PMID- 2582596 TI - A plasmatic factor may cause platelet activation in acute ischemic stroke. AB - To study the pathogenesis of platelet activation in ischemic stroke, ionized calcium ([Cai2+]) was measured in aequorin-loaded gel-filtered platelets in the basal and stimulated state. Basal [Cai2+] was increased in stroke patients maximally 36-72 hours after onset. The increase in [Cai2+] after stimulation with thrombin, collagen, and platelet-activating factor were also greater in stroke patients, but the profiles of these [Cai2+] changes were parallel to control. Cross incubation of control platelets with plasma from stroke patients resulted in raised basal [Cai2+] and caused the release of serotonin from platelets. These results indicate that the higher platelet basal [Cai2+] in stroke patients represents a lowered threshold for activation and that this may be due to a plasmatic factor rather than a primary platelet defect. PMID- 2582598 TI - Relation between sympathetic outflow and vascular resistance in the calf during perturbations in central venous pressure. Evidence for cardiopulmonary afferent regulation of calf vascular resistance in humans. AB - Vascular studies in humans have advanced the concept that, during orthostatic stress, cardiopulmonary afferents reflexly regulate vascular resistance in the forearm but exert surprisingly little if any effects on vascular resistance in the calf. In contrast, neurophysiological studies have indicated that unloading of cardiopulmonary afferents during lower body negative pressure evokes comparable increases in sympathetic outflow to the muscles of both the forearm and the calf. The aim of this study, therefore, was to determine if alterations in central venous pressure over the physiological range trigger reflex changes in muscle sympathetic outflow that not only are statistically significant but also are large enough to alter vascular resistance in the calf. To accomplish this aim, we measured calf blood flow with plethysmography and simultaneously performed microelectrode recordings of sympathetic outflow to calf muscles in conscious humans during maneuvers designed to alter the loading conditions of the cardiopulmonary afferents. We found that calf vascular resistance increased by 33 +/- 7% (mean +/- SEM, p less than 0.05) during decreases in central venous pressure produced by nonhypotensive lower body negative pressure (LBNP) and decreased by 26 +/- 5% (p less than 0.05) during increases in central venous pressure produced by nonhypertensive infusion of normal saline. These changes in calf resistance were at least as large as the changes in forearm resistance evoked by these maneuvers and were accompanied by parallel changes in peroneal muscle sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582599 TI - Morphometric analyses of rabbit thoracic aorta after poststenotic dilatation. AB - The aim of this study was to quantify the morphological changes in the arterial wall resulting from poststenotic dilatation (PSD). PSD was produced by placing a split nylon ring around the thoracic aorta of the rabbits at a level of T6-7 during a sterile thoracotomy done under pentobarbital anesthesia. After period of PSD ranging from 1-51 months these rabbits were anesthetized, as were the control animals, and the descending thoracic aorta from the fourth to the eleventh ribs was removed following perfusion fixation with Karnovsky's solution at a constant pressure of 80 mm Hg. The extent of PSD development was variable even though the stenotic ring was the same size in all rabbits. Ultrastructural findings showed degenerative changes of the wall components in the PSD region and were more prominent in the aortas with greater dilatation. Morphometric measurements showed that the PSD was accompanied by a decrease in volume density of both smooth muscle cells (SMCs) and elastin and an increase in collagen and ground substance. These changes were well correlated with degree of dilatation and ratio of internal radius to wall thickness (hence, mean wall stress) but not with duration of PSD. While the number of SMCs per unit volume in the PSD aortas was significantly less than normal (p less than 0.05), there was no significant change in mean cell volume. Although the reduced muscle mass might be expected to lower the capacity of the vessel to maintain tone, previous results show that this does not occur. PMID- 2582600 TI - Possible involvements of intracellular Ca2+ and Ca2+ -dependent protein phosphorylation in cholinergic differentiation of clonal rat pheochromocytoma cells (PC12) induced by glioma-conditioned medium and retinoic acid. AB - It is known that nerve growth factor (NGF) induces neurite outgrowth and elevation of the activity of adrenergic marker enzyme, tyrosine hydroxylase (TH) in clonal rat pheochromocytoma cells (PC12), whereas glioma-conditioned medium (GCM) induces neurite outgrowth and elevation of the activity of cholinergic marker enzyme, choline acetyltransferase (ChAT) in PC12 cells. In the previous study we have shown that retinoic acid (RA) induces specific elevation of ChAT activity and depression of TH activity without morphological differentiation (Matsuoka, I. et al., Brain Res., 502 (1989]. In the present study, we compared the effects of NGF, GCM and RA on the intracellular signalings in PC12 cells in relation to the mechanism of cholinergic differentiation. Addition of NGF, GCM or RA to the culture medium of PC12 cells caused a rapid rise in intracellular Ca2+ concentration [( Ca2+]i) reaching the level of almost 2.5-fold the resting condition within 3-18 h. Thereafter, [Ca2+]i of NGF-treated cells were decreased to the resting level within 12 h. On the other hand, [Ca2+]i of GCM-and RA treated cells decreased to a level which was 1.8- to 2-fold the resting condition within 24-48 h and stayed at this level for up to 4-7 days. When homogenates of GCM- and RA-treated PC12 cells were incubated with [gamma-32P]ATP, phosphorylation of a protein with molecular mass of 27 kDa (27 K-protein) was specifically enhanced. The phosphorylation of the 27 K-protein was not seen in the homogenate of the NGF-treated cells. The phosphorylation of the 27 K-protein was dependent on Ca2+ and inhibited by inhibitors of Ca2+-dependent protein kinase, H-7 and W-7. Addition of H-7 and W-7 to the culture medium of PC12 cells abolished the elevation of ChAT activity specifically induced by GCM and RA. These observations suggested that the sustained increase of [Ca2+]i and Ca2+ dependent protein phosphorylation are involved in the intracellular signaling mechanism required for the cholinergic differentiation of PC12 cells induced by GCM and RA. PMID- 2582601 TI - Intrinsic and extrinsic factors collaborate to generate driving forces for neural tube formation in the chick: a study using morphometry and computerized three dimensional reconstruction. AB - The formation of the neural tube, the rudiment of the entire central nervous system, is one of the earliest morphogenetic movements. The origin of the driving forces for this process remains uncertain, but recent studies suggest the involvement of both intrinsic and extrinsic factors. In the present study, we have used morphometry, analysis of stereopair photographs of whole embryos, and computerized three-dimensional reconstruction to investigate the factors which constitute the bulk of the driving forces for neural tube formation in the developing midbrain of Hamburger and Hamilton stages 5-9 chick embryos. Results support the notion that neural tube formation is driven by a coordinated interplay of intrinsic and extrinsic forces. Initial bending of the neural plate along the midline of the embryo and uplifting of the neural folds is accomplished primarily through the combined action of intrinsic forces (resulting from apical constriction of neuroepithelial cells) and extrinsic forces (mostly a passive consequence of head-fold formation). However, once in the uplifted position, curling over of neural folds and closure of the neural tube is driven largely by apical constriction-mediated (intrinsic) forces that are generated by cells in the midlateral walls of the forming neural tube. PMID- 2582602 TI - Changes in synaptic density in motor cortex of rhesus monkey during fetal and postnatal life. AB - The density and proportion of synaptic contacts in the primate motor cortex (Brodmann area 4) were determined in 21 rhesus monkeys ranging in age from embryonic day 41 (E41) to 20 years. Two to 4 vertical electron microscopic probes, each consisting of 150-250 overlapping micrographs traversing the thickness of the cortex, were prepared for each specimen. Synapses were categorized according to their morphology (symmetrical or asymmetrical), cellular location (on spines, shafts or soma), number, and ratio of laminar distribution. The density of synapses was expressed per unit area and volume of neuropil (excluding neuronal and glia cell bodies, myelin sheath, blood vessels and extracellular space). The first synapse in the area of the emerging motor cortex were observed at E53 in the marginal zone (prospective layer I) and in the transient subplate zone situated beneath the developing cortical plate. Around midgestation (E89) synapses were observed over the entire width of the cortical plate, and their density was about 5/100 microns 3 of neuropil. During the last two months of gestation synaptic density increased 8-fold across all layers to reach about 40/100 microns 3 at the time of birth (E165). Synaptic production continued postnatally and by the end of the second postnatal month attained a level of 60/100 microns 3 neuropil which is two times higher than in the adults. This level decreased at a slow rate until sexual maturity (3 years of age) and then more rapidly to the adult level which is characterized by relative stability of about 30/100 microns 3. The decline in synaptic density after the peak in infancy occurs predominantly at the expense of asymmetric synapses situated on dendritic spines; the population of symmetric synapses on dendritic shafts remains relatively constant. The development of synaptic connections in the motor cortex of non-human primates involves initial overproduction followed by selective elimination and structural alterations. PMID- 2582603 TI - Dendritic growth of DAPI-accumulating amacrine cells in the retina of the goldfish. AB - The dendritic growth of amacrine cells was studied in the retina of the goldfish. Those cells that accumulated the intraocularly injected fluorescent dye 4,6 diamidino-2-phenylindole (DAPI) were compared in retinal wholemounts from small and large animals. Dendritic arbors were stained by intracellular injections of Lucifer yellow. Based upon their dendritic morphology, two types were identified, radiate and fusiform. The dendritic field areas and the number of dendritic terminals were quantitatively compared for cells in small retinas from young fish and large retinas from old fish in the region of the retina that grows by expansion. For both cell types the dendritic fields were significantly larger in the large retinas. The radiate cells had the same number of dendritic terminals in retinas of both sizes, where the fusiform cells in the large retinas had significantly more dendritic terminals than those in the small retinas. This resulted from the addition of new dendrites to the proximal arbor. These data show that with retinal expansion the pattern of dendritic growth by a amacrine cells is cell-type specific. PMID- 2582604 TI - Do glucocorticoids induce adrenergic differentiation in adrenal cells of neural crest origin? AB - The chromaffin cells of the adrenal medulla originate in the neural crest and migrate to populate the emerging adrenal gland. When differentiated, the adrenal medulla is formed by two populations of cells: the norepinephrine (NE) cells, which contain the first 3 enzymes of the catecholamine pathway, and the epinephrine (Epi) cells, which contain all 4 enzymes. It has been suggested that in rat, the last enzyme, phenylethanolamine-N-methyltransferase (PNMT), appears in NE cells that are exposed to very high levels of fetal glucocorticoids (GCs), such as those present in the adrenal gland. If so, PNMT would appear during development after the initiation of fetal GC synthesis by the adrenal cortex at E18. In this study we examined the time of appearance and the relative level of PNMT mRNA and protein in rat embryos. We found (a) PNMT protein and mRNA are present at E16. Moreover, (b) the proportion of NE and Epi cells is already similar to that of adults and (c) the adult proportion of steady-state PNMT mRNA is also achieved prior to E18. We conclude that the appearance of PNMT is not affected by the surge of fetal GCs. Questions are raised as to the identity of the cues, genetic and/or epigenetic, which determine the differentiation of NE and Epi cells in the adrenal gland. PMID- 2582605 TI - HNK-1 marks earliest axonal outgrowth in Xenopus. AB - In wholemounts of the very early developing nervous system of Xenopus, HNK-1 specifically labeled cell bodies, axons, and growth cones of identifiable CNS neurons during the period of axonal outgrowth. The unique overview provided by these preparations showed that individual growth cones navigate their routes independently rather than by fasciculation and, further, revealed features of the directional and positional choices made by axons of several different but simultaneously developing pathways. PMID- 2582606 TI - Monoclonal antibody that binds to both the prenatal and postnatal astroglia in rodent cerebellum. AB - A monoclonal antibody (MAb), generated by immunizing mice with homogenized guinea pig cerebellum, labeled cerebellar astroglia including perikarya, radial fibers and veil-like processes in adult rats, mice and guinea pigs. Cell bodies and processes of the immature radial glia in the ventricular neuroepithelium of fetal mice cerebellum were definitely stained by the MAb on the 14th day of gestation. The astroglial components continued to show selective immunoreactivity to the MAb after the 14th day of gestation. PMID- 2582607 TI - Developmental changes in the pattern of retinal projections in pigmented and albino rabbits. AB - The distribution of retinal axons and/or terminals in the retino-recipient nuclei of pigmented and albino rabbits varying in age from the 24th postconceptional day (24PCD) to adulthood was examined following unilateral intraocular injections of the enzyme horseradish peroxidase. Both in pigmented and albino rabbits contralateral retinal axons and/or terminals in the dorsal and ventral lateral geniculate nuclei (DLG and VLG), superior colliculi (SC), pretecta (PT) and accessory optic tract nuclei (AON) were already present on 24PCD. In the period 26-30PCD the contralateral projection occupied the entire volume of the DLG, VLG and SC. Although 32PCD (the day of birth) the proportions of the volumes of DLG and VLG occupied by the contralateral projections were slightly reduced, their volume continued to increase in absolute terms up to adulthood. In pigmented rabbits the ipsilateral projections to all retino-recipient nuclei were most dense and extensive on 26PCD. From 26PCD, the relative extent of the ipsilateral projections was gradually reduced, but a reduction in their absolute extent did not become evident until 32PCD. By 32PCD the ipsilateral projection to the AON had disappeared completely. The distribution of ipsilateral axons and/or terminals and the relative proportion of the nuclei occupied by the ipsilateral projection in all other retino-recipient nuclei had become adult-like by 34PCD. In albino rabbits only a sparse ipsilateral projection to the presumptive superficial collicular layers was present on 24PCD. In the remaining retino recipient nuclei an ipsilateral projection was present on 26PCD. From 26PCD the relative extent and from 30PCD the absolute extent of ipsilateral retinal axons and/or terminals was gradually reduced. The relative extent of the ipsilateral projection had become almost adult-like by 34PCD. Throughout development ipsilateral projections in albinos were consistently less dense and less extensive than those in pigmented rabbits, and unlike in pigmented rabbits, the ipsilateral projections to the VLG and PT were only transient. The differences between the two strains in the pattern of retinofugal projections were further enhanced during the period of segregation of the ipsilateral and contralateral projections. Considering the fact that in both strains there is a partial correspondence between the period in which the spatial extent of the ipsilateral projections is reduced and the period of retinal ganglion cell (RGC) death, it is likely that RGC death plays a role in the process of segregation of the retinal afferents into ocular domains. However, our data suggest that other mechanism(s) also play an important role in the process. PMID- 2582609 TI - Consequences of visual deprivation in the absence of binocular competitive mechanisms in Siamese cat area 17. AB - The Siamese cat is a mutant with abnormally crossed visual pathways, which provides a model for studying the effects of visual deprivation in the absence of binocular competitive interactions. Siamese cats are known to be resistant to the effects of monocular eyelid suture. To further explore the nature of this resistance, the receptive field properties of neurons in area 17 of monocularly (MD) and binocularly (BD) deprived Siamese cats were studied. Neither condition produced a loss of cortical responsiveness, which is a characteristic result of binocular deprivation in normally pigmented cats. Somewhat more units in the deprived hemisphere of MD Siamese cats were orientation-selective, and many more units were direction-selective than in BD Siamese cats. This difference may be due to an effect of visual attentional mechanisms, which can function in MD but not BD Siamese cats. To test whether the resistance to the effects of visual deprivation in Siamese cats might be a more general phenomenon. Siamese and normally pigmented cats were raised in an 8-Hz stroboscopically illuminated environment. Both groups showed a severe loss of direction selectivity. Some of the normally pigmented cats also showed a loss of binocularity, which appeared to be secondary to strabismus. PMID- 2582608 TI - Dynamic structure of the radial glial fiber system of the developing murine cerebral wall. An immunocytochemical analysis. AB - Dramatic changes occur in the radial glial fiber system of the murine forebrain in the course of neocortical histogenesis. Initially, prior to substratification of cortical and subcortical anlagen between E13 and E14, the system is uniformly radial in alignment. It appears to achieve maximum density and to be highly uniform in structure throughout its radial span, both in terms of apparent fiber density and the pattern of arrangement of fibers in fascicles. Subsequent to E14, concurrently with rapid growth of the cerebral wall and with the differentiation of the cortical substrata and intermediate zone, the subcortical segment of the system becomes laterally arced while the transcortical span of the system remains radially aligned. Although the spacing between fascicles changes little, there is an apparent general drop in fiber density associated with a progressive reduction in the number of fibers per fascicle. The changes in relative positioning of the fibers and the apparent decline in fiber density are most dramatic within the developing cortical plate and subplate and may be of specific significance for the migration and radial assembly of the neurons in the supragranular neocortical layers. PMID- 2582611 TI - Molecular genetics and the transformation of clinical chemistry. AB - Clinical chemistry is going through an identity crisis, squeezed between automation (de-skilling) on the service side and molecular genetics in research. Automated routine estimations are now carried out and interpreted by machines; the skilled staff members required are more likely to have degrees in electronics than medicine or biochemistry. The role of molecular genetics is more ambiguous; it is inherently reductionist, in that it attempts to explain most clinical phenomena in terms of DNA sequence alone. This has been remarkably successful for single-gene defects (such as those causing Duchenne muscular dystrophy, hemoglobinopathies, cystic fibrosis, and ataxias) and may well prove equally so for Alzheimer's disease, cancer, heart disease, and schizophrenia. DNA diagnosis is not yet routine, but because of technical advances such as gene amplification ("PCR") and high-sensitivity gene-detection assays, it may soon become so, not only in major centers but also in local pathology laboratories and general practice. Clinical chemists must decide whether they wish to respond to this new and stimulating challenge by retooling and retraining. Should anyone be permitted into clinical chemistry during the 1990s without knowledge of both electronics and molecular genetics? Will there be a clinical chemistry in the twenty-first century other than through molecular genetics? This article is a personal response to these questions. PMID- 2582610 TI - Brainstem serotonergic hyperinnervation modifies behavioral supersensitivity to 5 hydroxytryptophan in the rat. AB - Rat pups were injected intracisternally (i.c.) or intraperitoneally (i.p.) with 5,7-dihydroxytryptamine (5,7-DHT) or saline and challenged 2 and 14 weeks later with the 5-HT precursor 5-hydroxytryptophan (5-HTP), which evokes behavioral supersensitivity in adult rats, 5,7-DHT induced transient postinjection convulsions in rats injected i.c. but not i.p. Rats with either type of 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP. However, rats lesioned by i.p. injections exhibited significantly greater shaking behavior (+1445%) in response to 5-HTP than their i.c. counterparts, who instead showed more forepaw myoclonus (+250%) and head weaving (+270%), the core features of the 5-HT syndrome. Differences in 5-HT syndrome behaviors were already present 2 weeks after lesioning, whereas the difference in shaking behavior was not. After 14 weeks, 5-HT was selectively depleted (-43 to -92%) in hippocampus, spinal cord, and frontal cortex, and differences between i.c. and i.p. 5,7-DHT routes were insignificant except in frontal cortex. Brainstem 5-HT concentrations were significantly increased (+35%) after i.p. 5,7-DHT injections in contrast to reduction (-89%) after i.c. 5,7-DHT; 5-hydroxyindole acetic acid/5 hydroxytryptamine (5-HIAA/5-HT) ratios were decreased (-20%) with either route. These data suggest that brainstem 5-HT hyperinnervation following i.p. 5,7-DHT injection modifies the functional consequences of injury in abating the 5-HT syndrome, but does not result in complete recovery since shaking behavior is enhanced. Loss of presynaptically mediated autoregulation or receptor dysregulation may play a major role in behavioral supersensitivity induced by 5 HTP in rats with 5,7-DHT lesions. To the extent that the 5-HT syndrome is mediated by 5-HT1A receptors and shaking behavior by 5-HT2 sites, differential responses to injury of 5-HT1A and 5-HT2 receptors may contribute to these behavioral differences. PMID- 2582613 TI - Characteristics of creatine kinase-MB and MB isoforms in serum after reperfusion in acute myocardial infarction. AB - Characteristics of CK-MB, the MB1 and MB2 isoforms, and the MB2/MB1 ratio are described in six acute myocardial infarction (AMI) patients in whom the infarct related artery was identified and, after intervention, normal coronary flow was re-established. After myocardial reperfusion, washout of CK-MB and the MB2 isoform occurred in parallel, with CK-MB peaking between 5.75 and 10.0 h, and MB2 peaking between 4.50 and 8.00 h. In five of the six patients, MB1 peaked between 8.75 and 15.5 h; the MB2/MB1 ratio demonstrated the earliest peak from 0.75 to 2.25 h. When we compared this study group to an additional 10 AMI patients who had achieved myocardial reperfusion earlier, we found a significant difference (P less than 0.005) for all tests, except MB1 isoform activity, as early as 50 min after reperfusion. This same comparison, by logistic-regression analysis, showed that the MB2/MB1 ratio discriminated between the groups 50 min after reperfusion (P less than 0.05); MB2 showed near-significance at 100 min (P less than 0.057); and CK-MB achieved significance after 200 min (P less than 0.05). CK-MB, the MB2 isoform, and especially the MB2/MB1 ratio show potential for the early, noninvasive detection of myocardial reperfusion. PMID- 2582612 TI - Factors affecting a cyanogen bromide-based assay of thiamin. AB - We analyzed extensively a modified thiochrome method for thiamin analysis. Acid phosphatase (EC 3.1.3.2) from potato was superior to either alpha-amylase or acid phosphatase from wheat germ as a dephosphorylating agent. Timing of cyanogen bromide exposure was important, but the assay had good precision and accuracy. The standard curve was linear from 10 to 3000 nmol/L. The within-run and between run coefficients of variation for total thiamin in whole blood were 3.6% and 7.4%, respectively. Analytical recoveries for low, intermediate, and high additions of thiamin to whole blood were 93-109%. Sample yield was increased by 41% (+/- 29% SD) with pre-assay freezing. Samples were stable for two days at room temperature, for seven days when refrigerated, and for two years when frozen. Previously unreported interference was seen with penicillin derivatives, and with several commonly used diuretic and antiepileptic medications. This assay may be suitable for population screening; 200 samples could be analyzed weekly at a cost of +0.20 per sample. PMID- 2582614 TI - Plasma glutathione S-transferase and F protein are more sensitive than alanine aminotransferase as markers of paracetamol (acetaminophen)-induced liver damage. AB - Concentrations of glutathione S-transferase (GST; glutathione transferase; EC 2.5.1.18) B1 subunits, F protein, and the activity of alanine aminotransferase (ALT; EC 2.6.1.2) were measured in sequential plasma samples taken from nine patients with self-administered paracetamol (acetaminophen) poisoning. GST exceeded the reference interval in all patients at the time of admission, and F protein was increased in seven. In contrast, abnormal activities of ALT in plasma were found in only one of the nine on admission, a patient admitted 12 h after poisoning. Subsequent to admission nine, eight, and five patients, respectively, had abnormal concentrations of GST, F protein, and ALT. When expressed as multiples of the upper reference limit, the highest values for GST measured in each patient always far exceeded the greatest abnormalities in ALT; this was true for F protein in only five patients. Patients in whom the concentration of GST exceeded 10 micrograms/L on admission subsequently went on to develop moderate or severe liver damage, despite treatment with N-acetylcysteine. F protein and ALT measurements on admission were not as efficient as GST at predicting the clinical outcome of the patients. We conclude that GST and F protein offer clear advantages over ALT for detecting minor degrees of acute liver dysfunction, particularly when only centrilobular damage may be involved. PMID- 2582616 TI - Automated DNA sequencing methods involving polymerase chain reaction. AB - Polymerase chain reaction (PCR) as a method for preparing DNA templates has been used for several DNA sequencing applications. An in situ procedure for directly sequencing PCR products by the dideoxy-termination method has been developed by using fluorophore-labeled sequencing primers. Completed sequence reactions were combined and loaded into a single electrophoretic lane of a fluorescence-based DNA sequence analyzer. DNA targets devoid of a universal primer sequence could be sequenced with labeled universal primers by incorporating a universal primer sequence into the PCR product. With this method, the sequence of a 351-bp region in the bacteriophage lambda genome was fully analyzed in a single lane with automatic base identification accuracy of greater than 99%. An unknown sequence, 1.7 kb long, also was sequenced by this procedure, in combination with a "PCR gene walking" strategy. Comparison of the 1110 bases in overlapping sequence data from both strands yielded only two single-base ambiguities. Automated DNA sequence analysis of the highly polymorphic HLA-DQA-1 (alpha) region in the human genome can be performed with this simple methodology. Use of this PCR-sequencing method to analyze DNA extracted from a one-month-old blood sample from an individual who is heterozygous at this locus allowed unambiguous assignment of genotype. PMID- 2582615 TI - Autoantibodies to lactate dehydrogenase in serum identified by use of immobilized protein G and immobilized jacalin, a jackfruit lectin. AB - In this method for identifying autoantibodies to lactate dehydrogenase (anti-LDs) in serum, we used immobilized Protein G to bind IgG-complexed LD and immobilized jacalin to bind IgA-complexed LD, leaving non-complexed LD in solution. The non complexed LD and total LD were kinetically measured. We report results as LD bound to immobilized Protein G and LD bound to immobilized jacalin. Using sera demonstrating IgG and IgA anti-LDs by immunoelectrophoresis (IEP), respectively, we optimized the method for incubation time and concentration of binding agents. We demonstrated concomitant binding of LD and greater than or equal to 98% of IgG and of LD and greater than or equal to 92% of IgA. For LD bound to immunobilized Protein G the detection limit was 10 U/L, within- and between-run CVs ranged from 2.9% to 9.1%, and values for normal sera were less than or equal to 3% of total LD. Results for LD bound to immobilized jacalin were similar. We tested 10 sera displaying aberrant LD electrophoretograms: In seven, LD bound to immobilized Protein G was increased (range: 26-99% of total LD), indicating IgG-complexed LD. This was confirmed by IEP, demonstrating IgG1,2, or IgG3 anti-LDs in these sera. In the other three sera, LD bound to immobilized jacalin was increased (range: 38 72% of total LD), indicating IgA-complexed LD. This was confirmed by IEP, demonstrating IgA anti-LDs in these sera. Evidently this method is an alternative to IEP for identifying anti-LDs in serum. PMID- 2582617 TI - Calciferin and cathepsin D-like acid protease in serum in acute and chronic liver injuries in rats and humans. AB - Serum from patients with chronic liver diseases (chronic hepatitis, cirrhosis, and hepatomas) contained greater concentrations of calciferin (total 1.7-fold, free 3.3-fold) than that from normal subjects. There were also decreases in the concentration and affinity of the calciferin-binding protein(s) in the patients' sera, but the amount of cathepsin D (EC 3.4.23.5)-like acid protease (total and free) was within normal limits. In addition, rats with acute liver injuries (partial hepatectomy or CCl4 administration) showed increases in calciferin and acid protease in their serum. Rats subjected to continuous feeding of 3'-methyl-4 dimethylaminoazobenzene (a potent hepatocarcinogen) also showed an increase of both analytes in the earlier stages (two to eight weeks; acute phase). Later (13 weeks or more; chronic phase), however, only acid protease appeared to return to normal values. PMID- 2582618 TI - Enzymatic assay of magnesium through glucokinase activation. AB - We describe an improved enzymatic method for assaying magnesium in serum, plasma, or urine. Magnesium participates as an Mg.ATP complex in a reaction catalyzed by glucokinase (EC 2.7.1.2) coupled to an NADP+-dependent glucose-6-phosphate dehydrogenase (EC 1.1.1.49) reaction. The increase of absorbance at 340 nm, due to the NADPH produced, is proportional to the amount of the activated glucokinase, which in turn is related to the concentration of magnesium in the sample. The method is characterized by a zero-order reaction kinetics, affording a simple and rapid assay with good sensitivity and linearity (up to 2.06 mmol/L) and by working solutions that are stable (refrigerated) for one month. The method is reliable, produces test results that compare closely with those of the atomic absorption spectrophotometry (r greater than or equal to 0.99), is suitable for routine work, and lends itself to automation. PMID- 2582619 TI - Effect of glycation of low-density lipoprotein on the immunological determination of apolipoprotein B. AB - Non-enzymatic glycation of low-density lipoprotein (LDL) may contribute to the premature atherogenesis of patients with diabetes mellitus. To assess whether glycation of apolipoprotein B, the predominant protein of LDL, interferes with the ability to immunologically quantify this protein, we prepared and purified glycated LDL by incubating normal plasma samples with high concentrations of glucose. Although both the plasma and the LDL specimens incubated with glucose contained significantly more glycated protein than control specimens, the quantitative interaction of an apolipoprotein B-specific antibody with glycated vs nonglycated LDL was not significantly different. We conclude that apolipoprotein B can be accurately quantified immunologically despite the presence of clinically excessive degrees of LDL glycation. PMID- 2582620 TI - A clinical chemistry analyzer evaluated by NCCLS guidelines for use in a military field laboratory unit. AB - In a previous comparison study of "dry chemistry" desktop analyzers, the ChemPro 1000 (Arden Medical Systems) was one of several instruments found suitable for field use. We have now evaluated the linearity, accuracy, and precision of the ChemPro 1000, according to NCCLS Document EP 10-P. We also compared results with those by the SMAC (Technicon) and the Nova 9 (Nova Biomedical) for electrolytes, serum urea nitrogen, and ionized calcium in field and laboratory environments. The precision (CV) of the ChemPro was within acceptable ranges for dry chemistry desktop analyzers for all analytes tested. This instrument is a suitable and reasonable alternative to manual chemistry or to large, automated instrumentation in a field environment. PMID- 2582621 TI - A rapid, automated micromethod for measuring free fatty acids in plasma/serum. AB - The investigation of mobilization and utilization of fat as fuel in human subjects requires the quantification of free fatty acids (FFA) in the circulating plasma. Methods in current use involve tedious extraction and titration, or enzymatic reaction with colorimetric or fluorometric detections. A rapid and reliable micro-technique is needed. We have adapted the manual enzymatic method of the Wako NEFAC kit to an automated rapid assay performed with a micro centrifugal analyzer. This method depends upon the specific acylation of CoA by FFA, followed by oxidation and condensation to form a purple adduct measurable at 550 nm. The acylation step requires incubation at 37 degrees C for 10 min, a critical step for serum/plasma analysis. Only 4 microL of plasma is needed, and 20 tests can be performed in 20 min. The precision (CV) of sample analysis is within 2%. The results for the samples analyzed by this technique are within 4% (SEM 1%) of results by the manual method. Thus accurate results are achieved at reduced cost, time, and sample size. PMID- 2582622 TI - An improved pyrogallol red-molybdate method for determining total urinary protein. AB - We adapted the pyrogallol red-molybdate method for total urinary protein to the Cobas Bio centrifugal analyzer. The method is simple, rapid, sensitive, and inexpensive. Addition of 25 mg of sodium dodecyl sulfate per liter to the reagent modifies protein reactivities so that the chromogenicity of human gamma globulins is the same as that of albumin. Results by this method and a comparison method that included gel filtration and a modified biuret reaction correlated well (r = 0.951). PMID- 2582623 TI - Comparative results with five cannabinoid immunoassay systems at the screening threshold of 100 micrograms/L. AB - Five commercially available immunoassay techniques were compared for the detection of cannabinoid metabolites in urine at a positive cutoff of 100 micrograms/L. Numerical values, available for four of these techniques, were used to evaluate inter-assay equivalence at this threshold. The total number of positive results differed for each assay, with some individual samples exhibiting wide variations in numerical values. As a group, the radioimmunoassay systems gave a greater proportion of positive specimens than did enzyme-linked or fluorescence-polarization-based techniques. The single threshold of detection suggested by federal guidelines does not provide for equivalent screening of cannabinoids with these immunoassay techniques. PMID- 2582624 TI - Changes in iron, zinc, and copper concentrations in serum and in their binding to transport proteins after cholecystectomy and cardiac surgery. AB - Concentrations of iron, zinc, and copper and of their respective transport proteins transferrin, albumin, and ceruloplasmin were measured in serum after elective cholecystectomy and cardiac surgery. The pattern of changes in the concentrations of iron, zinc, and copper was reproducible, with an early increase in serum iron and zinc, then a decrease in the concentrations as these metals are dissociated from their serum transport proteins. Zinc and iron concentrations change before the increase in C-reactive protein, which begins 8 h after incision, whereas the copper concentration in the serum remains constant in the early postoperative period. Quantitative and kinetic differences were observed in both the trace metal and protein changes after cardiac surgery and cholecystectomy. These studies indicate the complexity of interpreting changes in trace elements in serum after surgery. PMID- 2582626 TI - Ultra-specific time-resolved immunofluorometric assay of lutropin in serum. PMID- 2582625 TI - Performance of the Kodak iron and total iron-binding capacity methods. PMID- 2582627 TI - Cyclosporine does not interfere in total and high-density lipoprotein cholesterol measurement with use of enzymatic cholesterol assays. PMID- 2582628 TI - Simplified analysis for glycated hemoglobin by ion-exchange chromatography. PMID- 2582629 TI - Increases in aspartate aminotransferase and creatine kinase in hemorrhagic shock and encephalopathy syndrome. PMID- 2582630 TI - Serum creatine kinase in primary hypothermia. PMID- 2582631 TI - Conflicting results of liquid-chromatographic determinations of alkaline phosphatase isoenzymes. PMID- 2582632 TI - Nasal congestion during pregnancy. AB - Twenty-one pregnant women with nasal congestion, verified by rhinomanometry, did not differ significantly from 8 pregnant women without nasal congestion regarding the serum levels of the hormones oestradiol, progesterone and VIP. The congested group had a significantly lower serum level of oxytocin than the reference group. There were no differences in the symptoms urinary incontinence, constipation, and heartburn between the groups. The pathophysiology of nasal congestion during pregnancy is still veiled in obscurity. PMID- 2582633 TI - CT-scanning of the cochlea in Pendred's syndrome. AB - The inner ears of 5 adult patients with Pendred's syndrome were investigated using a Siemens SOMATOM DRG. Five normal hearing adults participated in the investigation as a control group. The CT-scanning comprised 10-15 consecutive scans of the cochlea. The CT evaluation was performed using both a special bone setting and a soft tissue setting. The cochlear content was quantitatively evaluated by drawing an irregular region of interest on the bone pictures. The region of interest was then transferred to the soft tissue pictures by means of the standard program of the CT-scanner. The resulting mean values of attenuation expressed in Hounsfield Units were significantly lower in the Pendred cochleas than in the normal cochleas. At the same time a typical Mondini malformed cochlea was demonstrated in all patients with Pendred's syndrome. The lower values of attenuation of the cochlea in Pendred's syndrome reflect the rudimentarily developed infra-cochlear osseous structures in this disease. We conclude that CT scanning of the cochlea using this procedure is reliable enough to replace the conventional axial-pyramidal tomography when a Mondini cochlea is suspected. PMID- 2582634 TI - The variable intrafamiliar expressivity in Pendred's syndrome. AB - This study presents clinical, audiological, radiological and biochemical data on 14 individuals representing 6 families, each including at least one patient with the classical Pendred's syndrome. The size of the thyroid, degree of hearing loss and result of the iodine perchlorate discharge test showed great variations, even between affected relatives. Based on these observations a new definition of Pendred's syndrome is proposed. The use of the iodine perchlorate discharge test for detection of healthy carriers among family members is suggested. PMID- 2582635 TI - Effect of surgical treatment of olfactory disturbance caused by localized ethmoiditis. AB - Twenty patients who had disturbance of the sense of smell caused by localized inflammation of the ethmoid sinus were studied to determine the effects of endonasal ethmoidectomy on olfaction. The patients were evaluated pre and post operatively regarding their subjective olfaction, and with the T&T olfactometry and the Alinamine intravenous administration test, both of which are widely used in Japan. The improvement rate was 70.0% subjectively and 80.0% with T&T olfactometry 6 months after surgery. It is concluded that surgery is worthwhile treatment for olfactory disturbances caused by localized ethmoiditis. PMID- 2582636 TI - Eustachian tube function following adenoidectomy: an evaluation by sniffing. AB - Recent investigations have demonstrated an association between sniff-induced negative middle ear pressure and otitis media with effusion. This is taken as evidence of Eustachian tube malfunction. Adenoidectomy is frequently performed as part of the surgical management for otitis media with effusion, but whether this affects Eustachian tube function is uncertain. The aim of this study was to investigate the hypothesis that if adenoidectomy improved Eustachian tube function, children who had undergone adenoidectomy would show less tendency to generate a high negative intratympanic pressure by sniffing. Eustachian tube function was studied actively in 40 children with otitis media with effusion. Twenty children, selected at random, underwent adenoidectomy and all 40 had a unilateral grommet inserted. Eighty-five percent of the children could create a negative middle ear pressure by sniffing, but there was no difference in the number of 'sniff + ve' children between the adenoidectomy and control groups (P greater than 0.5), or in the magnitude of the negative pressure induced. It is concluded that a high percentage of children with otitis media with effusion are capable of inducing a negative middle ear pressure by sniffing, but this parameter of Eustachian tube function is not affected by adenoidectomy. PMID- 2582638 TI - Tonsillectomy haemostasis: diathermy or ligation. AB - A retrospective and prospective study has been carried out to assess the morbidity associated with the techniques of diathermy and ligation in controlling tonsillectomy haemorrhage. No difference was found in the incidence of haemorrhage between the two techniques. The use of diathermy cuts the operation time by 26%, and has no increase in morbidity. PMID- 2582637 TI - Hearing-aids: can they be safely prescribed without medical supervision? An analysis of patients referred for hearing-aids. AB - A prospective study of 169 patients with hearing loss as their main symptom, referred to the ENT Clinic by General Practitioners, is reported. The study aimed to assess the safety of prescribing hearing aids by Physiological Measurement Technicians from the Audiology Department without medical supervision. The General Practitioners' referral letter and patients' histories were analysed to see if all cases of middle ear disease would be picked up from this information alone. In this study, 31 patients had otoscopic evidence of chronic otitis media, active or inactive, only 14 (45.2%) of whom were identifiable from the referral letters. Of the 8 cases of active inflammatory ear disease, 3 were not mentioned in the referral letter. No asymptomatic cholesteatoma was found in the study population. At present all patients are reviewed by ENT medical staff prior to prescription of a hearing-aid; we feel this should continue. PMID- 2582639 TI - Pneumatization of the posteromedial air-cell tract. AB - Sixty consecutive temporal bone specimens were examined histologically by light microscopy to determine the incidence of a pneumatized posteromedial air-cell tract extending into the posterior wall of the internal auditory meatus. Thirteen were found to have this air-cell tract. The main potential surgical hazards of opening this air-cell tract are CSF otorhinorrhoea and meningitis. PMID- 2582640 TI - Fibrin glue in the surgical treatment of ranulas. AB - The essential treatment of a ranula is meticulous dissection of the thin wall of the cyst in continuity with the sublingual gland of origin. We have used a technique of fibrin glue injection into the cystic space of the ranula after it had been evacuated by aspiration. The fibrin glue within the cystic cavity prevents collapse of the wall of the cyst during surgery and facilitates and simplifies the surgical procedure by clearly outlining the involved area and by sharply delineating its thin wall. PMID- 2582642 TI - The role of bacterial infection of the maxillary sinus in nasal polyps. AB - Fifty-two adult patients with nasal polyps were studied. All patients had preoperative sinus radiographs which were coded on the degree of mucosal thickening and these were compared with the results of irrigation of the maxillary sinuses. All irrigations were sent for culture and microscopy for pus cells. Pus cells and bacteria were found in only 16 of 104 wash-outs. It was concluded that the disease results in stasis of secretions and secondary maxillary sinusitis. PMID- 2582641 TI - Preglottic low-frequency Venturi jet ventilation in laryngoscopic microsurgery in adults. The influence of inspiratory time and frequency of ventilation. AB - The influence of inspiratory time and frequency of jet ventilation was investigated in an experimental model of a jet ventilator and a set of artificial lungs. The optimal ventilatory settings, when used in the clinical context, result in safe, adequate ventilation, as was proved by Astrup and intratracheal pressure measurements in 15 patients. PMID- 2582644 TI - Hearing loss in the elderly: a 17-year longitudinal study. PMID- 2582643 TI - Ear involvement in Wegener's granulomatosis. AB - In 16 of 19 patients with biopsy-proved Wegener's granulomatosis the early manifestations were limited to the ear and nose. The audiological data of 13 patients revealed middle ear involvement in 16 of 26 ears. Twenty-one of 26 ears presented with a low to moderate sensorineural hearing loss. One ear remained deaf after a sudden hearing loss in the early stage of the disease. Serologically, 4 of 6 tested patients with sensorineural hearing loss demonstrated antibodies against sarcolemma. One patient showed antinuclear antibodies. It is remarkable that these antibodies can often be detected in classic inner ear disorders. The course of inner ear function, serum findings and the success of immunosuppressive therapy in Wegener's granulomatosis are comparable with immunologically mediated vasculitis in the inner ear. PMID- 2582645 TI - The lamina propria and cholesteatoma. PMID- 2582646 TI - Survival of human immunodeficiency virus-infected patients on maintenance dialysis. AB - It has recently been reported that patients on maintenance dialysis with the acquired immune deficiency syndrome (AIDS) survive only 1 to 3 months. We studied all patients on maintenance dialysis at the Baumritter Kidney Center who were known to be infected with the human immunodeficiency virus (HIV). Five patients met the criteria for AIDS; another ten had anti-HIV antibodies but no opportunistic infections. The AIDS patients survived 8 to 18 months, and two are still alive. Mean survival in the AIDS group was 13.2 +/- 1.9 months, while the HIV(+) non-AIDS group survived 15.7 +/- 3.0 months. While these data are not statistically different, the survival curve in the AIDS group predicted a shorter survival than for the HIV(+) patients without AIDS. In fact, the survival of our dialyzed AIDS patients was similar to that reported for AIDS patients in general. Our experience suggests that dialysis may have no adverse effect on survival in AIDS. We conclude that dialysis patients with AIDS may survive 8 to 12 months or more and that the approach to such patients should be individualized. PMID- 2582647 TI - Remission of nephrotic syndrome in amyloidosis associated with a hypernephroma. AB - Nephrotic syndrome due to renal amyloidosis in association with hypernephroma underwent gradual but complete remission with loss of proteinuria after unilateral nephrectomy. Remission persisted for over five years despite the development of intracranial metastatic disease and the administration of dexamethasone, but relapse occurred 6 months before eventual death. This case history appears to be unique amongst the descriptions of tumor-associated amyloidosis. PMID- 2582648 TI - Renal functional reserve in patients with a reduced number of functioning glomeruli. AB - Renal functional reserve (RFR) has been reported to be either reduced or absent in patients with renal insufficiency. Our study consisted in measuring RFR by acute protein load (PL) in 3 groups of patients: the first one was composed of 20 patients (pts) with biopsy-proven glomerular disease (GN) and a varying percentage of sclerotic glomeruli (15-70%); the second one consisted of 10 patients with acquired single kidney (SK) and the third group contained 5 patients with surgical ablation of more than 50% renal tissue (LRRM). Twenty-four healthy volunteers were studied as control subjects. The GFR percentage increase (delta GFR%) after PL in CS did not differ from that of the three groups of patients, despite a significant difference in resting GFR (CS = 113 +/- 11 ml/min/1.73 m2: GN 72 +/- 28 ml/min/1.7, p less than 0.01 vs CS; SK 81 +/- 20 ml/min/1.73 m2, p less than 0.01 vs CS; LRRM 45 +/- 10 ml/min/1.7, p less than 0.01 vs CS; Moreover, an inverse correlation was not found either between GFR and the percentage of sclerotic glomeruli in GN (r = 0.01, p = NS) or between GFR and the extent of excised renal tissue in the other two groups (r = 0.38, p = NS). In conclusion, our data do not confirm that RFR is necessarily reduced or absent in patients with a reduced number of functioning glomeruli, nor do they uphold the hypothesis of constant hyperfiltration in the remaining glomeruli. PMID- 2582649 TI - Analysis of cellular populations in peritoneal effluents of children on CAPD. AB - The characterization of cellular populations in peritoneal effluents (PE) of CAPD patients has been the subject of few studies. In order to establish a possible correlation between PE cells and clinical parameters, we studied the immunocompetent cells that are found in uncomplicated patients. In this study we used cytofluorimetric analysis to characterize phenotypically immunocompetent PE cells. We studied 17 children with a mean age of 8.7 +/- 5.3 years, who had been on CAPD for a mean duration of 16 months. The patients never suffered from peritonitis. The effluents were collected after overnight dialysis and centrifuged to concentrate cells. Surface phenotype of PE cells was tested with a panel of monoclonal antibodies. The analysis of 40 PE samples showed that the various cell types were present with different frequencies, suggesting that a dominant phenotype cannot be defined. The ratio between M3 positive cells (monocytic-macrophagic lineage) and T3 positive cells (T lymphocytes) showed a tendency to decrease after initiation of CAPD. T4/T8 ratio in all samples did not differ from that of peripheral lymphocytes. A high frequency of activated T cells (41% +/- 13), defined by the presence of DR antigens on T3+ M3- cells, was seen in PE and confirmed by the high frequency of T cells expressing the IL-2 receptor. PMID- 2582651 TI - Head scan appearances and cognitive function in renal failure. AB - Cognitive function was assessed, and unenhanced CT head scans were carried out in 44 patients with renal failure. Thirteen had been on regular hemodialysis for 5 years or more (long-term hemodialysis group, LTHD), 12 had received hemodialysis for less than 5 years (short-term hemodialysis, STHD), 9 were on continuous ambulatory peritoneal dialysis (CAPD group) and 10 had severe chronic renal failure and were near to-but had not reached-dialysis dependence (chronic renal failure group, CRF). Employing an index of deterioration (the "discrepancy score") based on the discrepancy between current reading skills and current performance on the Wechsler Adult Intelligence Scale, 6 LTHD patients, 2 STHD patients, 2 CAPD patients and 5 CRF patients were identified as functioning below their predicted premorbid optimum level. Cerebral sulci were abnormally wide in 22 patients (8 LTHD, 2 STHD, 6 CAPD and 6 CRF) and one of the STHD group also had cerebral ventricular dilatation. Nine patients had both an abnormal scan and evidence of cognitive deterioration, 13 had an abnormal scan in the absence of such evidence and 6 had evidence of cognitive deterioration and a normal scan. Both cognitive deterioration and the CT scan finding of widening of cerebral sulci were commoner in these patients than would be expected in an age-matched sample of the general population, but no simple relationship was found between anatomical abnormality and cognitive functioning. Statistically significant correlations were found between discrepancy score and the cumulative amount of aluminum prescribed to be taken orally in both LTHD and CAPD groups. PMID- 2582652 TI - Comment on "Baroreceptor, not Left Ventricular, Dysfunction is the Cause of Hemodialysis Hypotension" by Heber et al. PMID- 2582653 TI - Pathophysiology and management of unstable angina. PMID- 2582650 TI - Campylobacter pylori: prevalence and significance in patients with chronic renal failure. AB - Since gastric symptoms are frequent in uremic patients, we have studied the prevalence and significance of Campylobacter pylori infection in patients with chronic renal failure. The prevalence of serum IgG antibodies to C. pylori in 50 patients on regular dialysis treatment (44%) was similar to that of a control group of 40 blood donors (45%), but was significantly lower (p = 0.0001) than that in 31 patients with peptic ulcer disease (93%). Furthermore, 11 of the 50 patients with chronic renal failure and a history of documented peptic ulcer disease had a similar prevalence of antibodies to C. pylori (45%) as did the 39 chronic renal failure patients without previous peptic ulcer (44%), which was significantly lower (p less than 0.01) than that in the control group of peptic ulcer patients (93%). Of 10 patients with chronic renal failure (6 with and 4 without gastric complaints) studied by endoscopical biopsies, two had chronic active antral gastritis and were positive for C. pylori by histology, culture and had IgG antibodies in their sera, while one patient with normal antral mucosa had IgG antibodies but was negative by culture and histology. Thus, this study shows that there is no predisposition to C. pylori infection among patients with chronic renal failure, and that C. pylori infection does not play a significant role in the ulcer diathesis in these patients. PMID- 2582654 TI - Doppler echocardiographic assessment of transmitral gradients and mitral valve area before and after mitral valve balloon dilatation. AB - This is a comparative study of 60 sets of observations of mitral valve end diastolic gradient, mean diastolic gradient, and mitral valve area obtained by Doppler echocardiography and cardiac catheterization. The studies were performed in 28 patients, 16 of whom underwent mitral valve balloon valvuloplasty. These 16 patients had studies performed before, immediately after valvuloplasty, and one week later. Thus 28 studies were performed before or without valvuloplasty (Group I) and 32 after valvuloplasty (Group II). The time interval between Doppler echocardiography and cardiac catheterization was less than 24 hours in 44 studies and 24 to 72 hours in 16 studies. In Doppler echocardiography the gradients were obtained by simplified Bernoulli's equation and the mitral valve area by pressure half-time method. There was excellent correlation between end-diastolic gradients (r = 0.96, p less than 0.001) and mean diastolic gradients (r = 0.92, p less than 0.001) measured by the two techniques. A statistically significant correlation also existed in the mitral valve area values (r = 0.53, p less than 0.005). On separate analysis Group I showed excellent correlation for all three variables (r values of 0.90, 0.87, and 0.82 for end-diastolic gradients, mean-diastolic gradients, and mitral valve area, respectively). Group II also showed excellent correlation of end-diastolic gradients (r = 0.80) and mean diastolic gradients (r = 0.87), but poor correlation of the mitral valve areas (r = 0.17; p = NS) by the two techniques. Doppler echocardiography can accurately measure transmitral gradients both before and after valvuloplasty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582655 TI - Cardiovascular reactivity and silent ischemia in response to mental stress in symptomatic and asymptomatic coronary artery disease patients: results of a pilot study. AB - The current study was designed to examine cardiovascular reactivity to psychological tasks and its relationship to provocation of ischemia in asymptomatic coronary artery disease (CAD) patients with documented silent ischemia and those with painful ischemia. ECG, heart rate, and blood pressure responses to mental stress were collected for 13 patients with coronary artery disease (CAD) and for 6 healthy control subjects. Six of the CAD patients were asymptomatic (documented silent ischemia and no history of angina), while the remaining 7 were symptomatic (history of angina). Three types of mental stress were employed: white noise (a passive stressor), digits repeated backwards (an active stressor), and a math task plus white noise (active + passive stressor). Results indicate that significant increases in heart rate and blood pressure, but not silent ischemic episodes, were induced by the mental stress tasks. In addition, patients with documented exercise-induced and ambulant silent ischemia showed trends of blunted autonomic responsiveness to the stressors. On the digits backwards task, the CAD patients with silent ischemia showed significantly lower diastolic blood pressure responses compared with controls or angina patients. Findings suggest that ischemic episodes are not easily induced by brief mental stress. However, results indicate that asymptomatic CAD patients with silent ischemia may be lacking in autonomic responsiveness, particularly in terms of peripheral resistance, to mental stress in comparison with health controls and symptomatic ischemic patients. Further investigation is needed to explore how patients with silent ischemia typically respond autonomically to mental stress and how blunted reactivity may relate to the provocation of unrecognized ischemic episodes. PMID- 2582656 TI - Elevated pain threshold in patients with effort-induced angina pectoris and asymptomatic myocardial ischemia during exercise test. AB - The purpose of the present study was to analyze the prevalence of asymptomatic (silent) myocardial ischemia during exercise testing among patients with effort induced angina pectoris, and further, to compare the pain threshold of patients with symptomatic and asymptomatic myocardial ischemia. A group of 26 patients comprised the study. In half of the patients myocardial ischemia during the exercise testing was silent and in one half it was symptomatic. Asymptomatic myocardial ischemia was defined as an asymptomatic ST-segment depression greater than or equal to 0.1 mV, lasting longer than 60 s during an exercise test. In patients with asymptomatic ischemia the pain thresholds both on toe and finger were significantly higher than in patients with symptomatic ischemia: mean values were 10.1 versus 4.9 mA on the toes, p less than 0.025, and 8.4 versus 2.5 mA on the fingers, p less than 0.01. We conclude that asymptomatic myocardial ischemia during exercise test is seen often in patients with angina pectoris and that this may be due to an increased pain threshold. PMID- 2582657 TI - Prognostic significance of postinfarction arrhythmias and biventricular dysfunction under stress. AB - The prognostic relevance on mortality of right ventricular dysfunction in comparison with left ventricular function during stress, complex arrhythmias detected by Holter monitoring, and variables of exercise performance, was evaluated via a retrospective follow-up of more than four years for cardiac mortality of all patients in the chronic stage after myocardial infarction who were referred serially during a one-year period to stress radionuclide ventriculography and 24-h Holter monitoring. A sample of 47% (213) of all patients admitted after myocardial infarction to the rehabilitation center during 1983 was investigated by scintigraphic stress testing and Holter monitoring and were followed up. Subsequent medication and invasive therapeutic interventions were documented. The mortality during a mean follow-up period of 3.9 years in 213 patients (mean age, 56 years) was 14.6%. Significantly decreased values of left and right ventricular ejection fractions during stress scintigraphy (38 +/- 14 versus 50 +/- 15%, p = 0.000 and 45 +/- 13 versus 54 +/- 11%, p = 0.001, respectively) were revealed in the cardiac deceased patient cohort compared with the remainder. Complex arrhythmias during Holter monitoring occurred twice as often (62 vs. 34%, p = 0.0059) in later deceased patients. Lifetable analysis demonstrated that patients with biventricular stress dysfunction had a significantly worse survival prognosis than those with monoventricular dysfunction. Multivariate nonlinear Cox survival analysis revealed that left and right ventricular ejection fraction during stress and arrhythmias were of independent prognostic significance compared with multiple clinical variables including those of exercise performance. Thus, apart from left ventricular dysfunction and arrhythmias, scintigraphically assessed right ventricular stress dysfunction is a further marker of poor prognosis after myocardial infarction. This reflects the previously neglected pathophysiologic significance of right ventricular performance in patients after myocardial infarction. PMID- 2582659 TI - Traumatic thrombosis of the left main coronary artery and myocardial infarction caused by blunt chest trauma. AB - We report the case of a 38-year-old man who, after a blunt chest trauma, developed an acute transmural myocardial infarction. Coronary arteriography revealed a thrombus in the left main artery, occlusion of the distal left anterior descending artery, and a diagonal branch caused by emboli. PMID- 2582658 TI - Structure and function of contractile proteins in human dilated cardiomyopathy. AB - The pathogenesis of reduced systolic left ventricular function in dilated cardiomyopathy is yet unclear. To analyze a possible involvement of contractile protein, function and structure of left ventricular myofibrils were examined in hearts of patients with advanced cardiomyopathy undergoing heart transplantation and in normal control hearts (from renal transplant donors). Myosin and actin content of the left ventricular myocardium was slightly reduced in cardiomyopathic hearts. Myofibrillar polypeptide composition was determined using two-dimensional electrophoresis and immunoblotting. No differences in constituting polypeptides were apparent, including Z-line proteins and proteins of the endosarcomeric lattice. M-line-bound creatine kinase was identical in both groups. Further, basal and maximal myofibrillar adenosine triphosphatase (ATPase) activities were unaltered in dilated cardiomyopathy. The structure of purified myosin was identical in both groups by the following criteria: electrophoretic mobility of native myosin, identical pattern of light chains after isoelectric focusing, identical cleavage peptides of myosin's heavy chain, and identical patterns after immunoblotting of heavy chain cleavage peptides using polyclonal antibodies generated against myosin from normal and cardiomyopathic ventricles. Ca2+-activated, K+-EDTA-activated and actin-activated myosin ATPase activities were identical in control and cardiomyopathic hearts. A structural alteration or functional defect of myofibrils does not seem to be primarily involved in the pathogenesis of reduced myocardial contractility in dilated cardiomyopathy. PMID- 2582660 TI - 1989 proceedings of the Hip Society. PMID- 2582661 TI - The effect of indomethacin, aspirin, and ibuprofen on bone ingrowth into a porous coated implant. AB - Therapeutic doses of indomethacin, aspirin, and ibuprofen were administered to New Zealand White rabbits after implantation of a porous-coated chrome-cobalt implant. Quantitative histomorphometric analysis was used to calculate the amount of bone occupying the pores. There was a statistically significant decrease in bone ingrowth in animals treated with indomethacin, ibuprofen, and high-dose aspirin when compared to a control group. There was a dose-response effect for the indomethacin and aspirin groups, with higher doses having a greater inhibitory effect. Indomethacin, ibuprofen, and high-dose aspirin may be contraindicated during the immediate postoperative period in patients having cementless arthroplasty. PMID- 2582663 TI - Examination of rotational fixation of the femoral component in total hip arthroplasty. A mechanical study of micromovement and acoustic emission. AB - Rotational loosening has recently emerged as an important cause of failure of the femoral component of total hip arthroplasties. This study was designed to investigate the role played by torsional loads in loosening of cementless femoral components and to evaluate three cementing techniques involving a combination of canal irrigation, manual insertion, and vacuum mixing combined with pressure injection of the cement for their ability to improve rotational fixation. Rotational micromotion and subsidence were measured in 24 preserved human anatomic specimen femora. Acoustic emission (AE) technique was applied as a non destructive method for evaluating material failure during loading. From the micromovement data, torque to 50 mu subsidence and torque to failure were surprisingly low with cementless fixation and with poor cement technique but were markedly improved with pulsed irrigation. Further improvement was achieved by pressure injection and vacuum mixing of the cement. However, AE was detected even in the most carefully performed cement specimens under torsional-loading conditions commonly occurring in daily activities. These signs of microfailure of the cement mantle at relatively low torsional loads suggest that the mode of failure of deeply penetrated cement is by microfracture of the cement mantle. The poor performance suggests that cementless fixation of intramedullary stems provides unsatisfactory fixation against torsional loading. There is need for major improvements in fixation mechanisms and techniques. The signs of failure of the cement mantle at normally occurring torsional loads suggest that even the best cement technique is prone to failure in torsion when exposed to normal daily use. PMID- 2582662 TI - Cementless press-fit cup. Principles, experimental data, and three-year follow-up study. AB - The concept of the press-fit cup includes an operative defect as small as possible, achievement of intrinsic stability by press-fit, and surface coating by an orderly, oriented wire mesh coating. The design is a modified hemisphere with flattening in the pole area and oversized cup diameter. A first series of press fit cups were fitted with titanium nitride-coated stainless steel mesh. The manufacturing of such chemically pure titanium has only recently become feasible. Animal experiments using mountain sheep have shown an increase in the stability of the press-fit cup within the acetabulum with time and progressive bony ingrowth; this was verified in cups retrieved at autopsy. Three hundred eighty seven first-generation titanium nitride-coated stainless steel mesh implants have been reviewed with a follow-up time of 12 to 39 months (average, 16.6 months). There were no intraoperative complications related to the cup. The roentgenographic follow-up study of 330 (85.1%) hips showed only a single case with a radiolucent line in all zones (1-3) as a roentgenographic sign of loosening, i.e., fibrous ingrowth. Two cups had to be revised due to insufficient primary stability and tilting. PMID- 2582665 TI - Cementless total hip arthroplasty using the anatomic medullary locking stem. Results using a survivorship analysis. AB - Three hundred forty-three primary hip arthroplasties performed prior to June 1984 were followed for two years, and an additional 204 were followed for five years. Anteroposterior and lateral roentgenograms taken at annual intervals were used for comparison. At two years, 78% of the hips showed roentgenographic signs of stem osseointegration. Seventeen percent were clinically stable but demonstrated reactive lines surrounding the porous surface, indicating lack of bone-ingrowth fixation. Four percent showed late implant migration. Using late migration as an end point, a survivorship analysis of the stem stability was performed. The cumulative survival rate for stable fixation was 94% at five years and 88% at eight years. Among the 143 undersized stems, 17 showed late migration and two failed by stem fracture at six and eight years, giving a cumulative survival rate of 77% at eight years. By contrast, there were no roentgenographic failures among 200 canal-filling stems. Three stems were revised: two for stem fracture and one for loosening with infection. Proximal stress shielding occurred only in bone ingrowth stems and was slightly progressive. Unstable implants produced progressive intramedullary canal widening. The clinical results were superior when the roentgenograms showed signs of bone-ingrowth fixation. Functional recovery in such cases was equivalent to that for cemented arthroplasty. PMID- 2582664 TI - Biomechanical and histologic investigation of cemented total hip arthroplasties. A study of autopsy-retrieved femurs after in vivo cycling. AB - Eleven whole anatomic specimens of the femur were retrieved at autopsy from patients who previously had cemented total hip arthroplasty. Implant duration ranged from 0.5 to 210 months. Clinically and roentgenographically the implants were stable. A detailed biomechanical analysis evaluated bone strains and implant stability in both the single-limb stance and stair-climbing positions using a 100 pound spinal load. The stability offered by cement in these well-fixed prostheses was remarkable, with the maximum axial micromotion being 40 mu. This is a reflection of intimate osseointegration at the bone-cement interface with only rare intervening fibrous tissue. The strain gauge and photoelastic strain-coating studies revealed that marked stress shielding in the proximal medial femoral cortex persists long after a cemented femoral component is inserted. Even 17 years after surgery, the strain in the calcar region did not normalize. PMID- 2582666 TI - Short-stemmed uncemented femoral component for primary hip arthroplasty. AB - A short-stemmed femoral implant differing from conventional design assumptions demonstrates that immediate three-point proximal femur fixation is possible without stem fixation. A double-wedged contour and neck shaft angle of 150 degrees help secure immediate stability and lessen an excessive varus moment. Results of 20 patients with at least one year of follow-up study are encouraging. Nineteen (95%) are classified as satisfactory with a Harris hip score of 44.5 before and 97.8 after surgery. One patient was revised for loosening; no patient has thigh pain. The gratifying early results justify further clinical investigation. PMID- 2582667 TI - A finite-element analysis of the effects of intertrochanteric osteotomy on stresses in femoral head osteonecrosis. AB - The efficacy of osteotomy for the precollapse stage of femoral head necrosis depends on altering load transmission. The alteration must reduce the stress levels on the infarcted bone during the process of repair. The prospects for success in this regard would likely be improved by the ability to predict reliably the stress changes derived from specific osteotomies for specific femoral head involvement patterns. For this reason, an anatomic three-dimensional finite-element model has been designed to compute necrotic femoral head stress changes that accompany varus, valgus, and rotational osteotomies. Four specific patterns of femoral head infarction are considered. Comparison of the patterns of load transmission at ten discrete instants (spanning the stance phase of the gait cycle) revealed that the critical stresses in the most commonly infarcted anterolateral and central femoral head regions occur just after the instant of heel-strike. For the femoral head with a deep, narrow lesion in the weight bearing tract, and for classic wedge-shaped segmental infarct, the data showed that 30 degrees varus osteotomy was beneficial in reducing stress levels through much of the infarcted region. The 30 degrees valgus osteotomy was less successful. Neither 30 degrees anteversion nor 30 degrees retroversion osteotomies caused substantial changes in stresses for infarcted regions along the weight-bearing tract. For the case of a wide, shallow lesion or for whole femoral head involvement, none of the four osteotomies considered was able to achieve appreciable net reduction of stresses in weakened, infarcted regions. PMID- 2582668 TI - Osteonecrosis of the femoral head. Results of core decompression and grafting with and without electrical stimulation. AB - The effectiveness of core decompression and bone grafting with and without electrical stimulation was investigated in patients with avascular necrosis (AVN) of the femoral head. One hundred sixteen hips with AVN had decompression and grafting; 74 were also treated with direct current (DC). The DC stimulation was via a coil inserted directly into the femoral head. These were compared to 55 hips with AVN treated nonoperatively. Hips treated with electrical stimulation showed less roentgenographic progression and achieved a better clinical score than hips treated with decompression and grafting alone. Both groups had a significantly lower incidence of arthroplasty than the nonoperated controls. One patient developed a pulmonary embolus, but there were no fractures or other complications. Decompression and grafting are safe and reasonably effective in retarding the progression of AVN. Supplemental electrical stimulation seems to improve the results even further. PMID- 2582670 TI - Hybrid total hip arthroplasty. AB - One hundred twenty-six primary total hip arthroplasties composed of a hybrid cemented femoral component and a cementless acetabular component were followed for a minimum of two years (mean, 42 months). The average patient age was 63 years. The most common diagnosis was osteoarthritis (85 hips), although 13 of the cases were severe or total congenital dislocations. Overall, the results were excellent. The mean Harris hip score was 93. Postoperative pain was rated as none or slight in 94% of the cases. No patient had moderate or severe pain. No femoral or acetabular components were revised. Roentgenographically no femoral component was definitely or probably loose. One acetabular reconstruction component had migrated. The authors conclude that the selective use of cemented and cementless fixation by anatomic site in this hybrid form of hip arthroplasty provided excellent results for five and one-half years. PMID- 2582669 TI - The conservative treatment of osteonecrosis of the femoral head. A comparison of core decompression and pulsing electromagnetic fields. AB - Once roentgenographic changes are apparent, osteonecrosis of the femoral head in the adult generally progresses to osteoarthritis within two to three years. A variety of conservative surgical procedures have been devised to conserve the femoral head with varying success. This study examines the effectiveness of pulsing electromagnetic fields and core decompression in the treatment of osteonecrosis of the femoral head. Both techniques reduce the incidence of clinical and roentgenographic progression. Exposure to pulsing electromagnetic fields appears to be more effective in hips with Ficat II lesions than in hips with more advanced lesions. PMID- 2582671 TI - Indications and results of intertrochanteric osteotomy in osteonecrosis of the femoral head. AB - The intertrochanteric osteotomy has been used for several years as a method of treatment of osteonecrosis of the femoral head. As the clinical experience has increased, it has become apparent that, if the procedure is to succeed, specific criteria have to be met. In general, a valgus/flexion osteotomy should be done in patients younger than 40 years who have a Ficat Stage II and/or crescent sign. A necrosis angle of less than 200 degrees as measured on anteroposterior and lateral roentgenograms is also important in predicting a successful outcome. Caudal oblique roentgenograms also help determine the status of the posterior femoral head and whether the osteotomy is feasible. Preoperative planning is important to reduce operating time and obtain a good end result. A 95 degrees blade-plate is used, and if necessary, a small wedge is excised to ensure coaptation of the osteotomy segments. The results of the procedure in 17 patients show that eight patients have a satisfactory result at a mean of three years, while three patients continue to have problems. Five patients have been converted to total hip arthroplasties, and one has a girdlestone arthroplasty. The unsuccessful results occurred in patients who were on corticosteroids or had continued metabolic bone abnormalities. Present experience confirms reports of other series. The operation should be offered only to the small group of patients with idiopathic, posttraumatic, or alcohol-induced osteonecrosis of the femoral head. PMID- 2582672 TI - Efficacy of intermittent epidural morphine following posterior spinal fusion in children and adolescents. AB - Postoperative pain is a distressing and disabling feature of scoliosis surgery. Epidural morphine has recently been advocated to reduce the frequency and severity of postoperative pain in adults. A retrospective study of 35 patients was conducted to determine whether epidural administration of morphine is useful in the management of postoperative pain in children and adolescents following posterior spinal fusion. The derived data included dose and frequency of narcotic administration on the day of surgery and during the subsequent three days. On the first postoperative day, the total morphine given averaged only 16.4 mg in patients receiving epidural morphine compared to 27 mg in those receiving only conventional parenteral morphine. Similar significant differences persisted through the second postoperative day. Intermittent epidural injection of small doses of morphine can give satisfactory and prolonged analgesia for early postoperative pain management. PMID- 2582673 TI - Bipolar implant shoulder arthroplasty. Long-term results. AB - The bipolar shoulder implant (BSI), designed by the senior author in 1975, has an unfixed metal glenoid cup with a polyethylene liner that articulates with a cemented titanium humeral component. The BSI was inserted in 35 shoulders of 33 patients with severe rheumatoid arthritis (20 cases), degenerative arthritis (ten cases), and posttraumatic lesions (five cases). The follow-up period ranged from 24 to 140 months (average, 63 months). Pain relief was good to excellent in 31 shoulders; four experienced some pain during daily activities. After BSI, motion was greatly improved with 71 degrees average range of abduction, 23 degrees range of adduction, 79 degrees range of flexion, 45 degrees range of extension, 76 degrees range of internal rotation, and 28 degrees range of external rotation. BSI was well-tolerated by the bone and soft tissues, with no erosive changes at the coracoacromial arch. There was no evidence of loosening at the cement-bone interface. One patient with a postoperative subcoracoid dislocation maintained a good functional result for more than 11 years. One BSI had draining sinus tract with negative culture, which spontaneously healed following removal of the implants. There were 3.3 mm (range, -7 mm to 11 mm) of superior subluxation of the humeral head on the preoperative roentgenogram. This increased to 8.7 mm (range, -5 mm to 20 mm) in the long-term follow-up roentgenogram. The bipolar implant is specially indicated in the severely arthritic shoulders in patients with vertical humeral subluxation and complicated histories of multiple failed operations. PMID- 2582675 TI - Treatment of subtrochanteric fractures of the femur treated with the 95 degrees angled blade plate. PMID- 2582674 TI - Posterior subtalar joint arthrography. A useful tool in the diagnosis of hindfoot disorders. AB - Obscure hindfoot disorders are often classified under the heading of sinus tarsi syndrome (STS). The diagnosis of STS is based upon subjective symptoms: tenderness over the lateral aperture of the sinus tarsi and hindfoot instability. Arthrography of the posterior subtalar joint is an objective parameter, identifying peri- or intraarticular pathology as the cause of symptoms. In 27 patients with STS, the pathologic arthrographic findings include less-marked microrecesses in the sinus tarsi region, ganglions at the anterior aspect of the subtalar joint, retraction of the joint recesses, a smooth and rounded appearance of the capsule, and a frozen subtalar joint. Through analysis of these films, the appropriate therapeutic approach can be outlined; infiltrations into the sinus tarsi itself, intraarticular corticosteroid injections, or subtalar arthrodesis for resistant cases are the procedures of choice. In the authors' experience, surgical curettage of the sinus tarsi has no place in the treatment of STS. PMID- 2582676 TI - Noncemented acetabular revision arthroplasty using allograft bone. AB - The authors retrospectively reviewed a series of 106 acetabular revisions for failed cemented total hip arthroplasties followed from 12 to 56 months. All of the sockets had extensive bone deficiency requiring bone graft surgery. The deficiencies were classified as cavitary, combined cavitary and segmental, and pelvic discontinuity. The purpose was to evaluate clinical experience with three different acetabular components. In chronological order, the three components tested were bipolar type, truncated-cone screw-in type, and porous-coated titanium press-fit type with fins. These were combined with four different bone augmentation constructs, using nonstructural morselized fresh-frozen allograft or segmental freeze-dried allograft. Follow-up evaluation of both the bipolar and screw-in designs showed frequent migration with bone graft resorption, compromising the clinical scores and leading to some revisions. The press-fit design had little migration, reliable graft healing, and better clinical scores. No revisions have been done. The nonstructural morselized bone allograft fared better under stable cups. The large segmental grafts did much better when buttress plating was combined with interfragmentary screw fixation compared to screws alone. PMID- 2582677 TI - Arthroscopy of the hip. AB - Arthroscopy of the hip is a relatively new addition to the orthopedic armamentarium. Eriksson, of Sweden, has been a pioneer in studying the force needed to distract the hip joint to allow adequate arthroscopic viewing. Johnson, of Michigan, has provided information on techniques including landmarks, needle positioning and cannula entry. Glick, of California, has described the lateral position for ease of entry of arthroscopic instruments just superior to the greater trochanter. A mini-arthrotomy technique has been used to sublux the femoral head anteriorly from the acetabulum to allow anterior viewing and debridement. An initial series of such procedures in 12 patients resulted in general improvement in symptoms of younger patients with localized articular cartilage defects. Results in older patients with diffuse osteoarthritic changes involving most of the weight-bearing zone of the femoral head were unsatisfactory, however, with most of those patients requiring total hip arthroplasty, within one to two years. Recently, arthroscopy of the hip has been performed in the outpatient surgery department under general endotracheal anesthesia in the lateral decubitus position. Mechanical distraction with 9-18 kg of force has been used routinely, without postoperative neurologic symptoms. Specially adapted long arthroscopes and powered synovial resectors and abraders have been used. In addition, pressurized saline inflow with 100 mmHg of pressure has provided improved joint visualization. Especially helpful has been the availability of angled arthroscopes, including 30 degrees, 60 degrees, and 90 degrees arthroscopes. Potential complications include inadvertent cartilage scuffing, broken instruments, neovascular injury to nearby structures, and local infection. Systemic complications such as pulmonary embolus must always by considered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582678 TI - Preliminary results of an off-the-shelf press-fit stem. The anthropometric total hip femoral component using exact-fit principles. AB - The use of custom-manufactured femoral prostheses as part of routine total hip arthroplasty (THA) has been suggested. However, there are several disadvantages, including possible inaccuracy of fit, inadequate instrumentation, and high cost. A series of 28 THAs (including 18% for revision of failed, cemented THA) using a press-fit prosthesis of contemporary design were investigated. The average follow up period was 28 months (range, 12-49 months). Clinical results were overall very good, even in revision cases. Roentgenographic changes included rapid femoral remodeling, which may increase component stability. Given the clinical and roentgenographic results obtained in this complex-problem patient population, it is difficult to justify the use of custom femoral components in routine THA. PMID- 2582679 TI - Shape the implant to the patient. A rationale for the use of custom-fit cementless total hip implants. AB - Most authors agree that "fit" and "fill" of the endosteal canal is critical to the success of cementless femoral components. Yet, there exists a wide variation to the anatomic size and shape of this canal in the normal population. This paper reviews the rationale and the efficacy of using a computed tomography-generated CAD/CAM custom femoral component in cementless total hip arthroplasty. One hundred fifty-six cases (81 primary and 75 revisions) were reviewed with follow up time of six weeks to three years (mean, 22 months). A subset of 48 hips (25 primary and 23 revisions) has been followed a minimum of two years. For the primary hips, the custom group was found to have statistically higher Harris pain scores (less pain) at all follow-up intervals as compared to a prior series by the same surgeon using an off-the-shelf (OTS) prosthesis. Revision customized hip implants had lower Harris pain and total scores than primary custom hips, but 80% were in the none or slight pain category. In revision cases, the use of custom components decreased the need for structural bone grafting and achieved stability on host bone in situations in which it was not possible using OTS components. Complications included failure by aseptic loosening of one primary and one revision case. Initial subsidence of more than 3 mm of the collarless custom design occurred in 8%, the majority being in revision cases. All cases but one appear to have stabilized. Subsidence occurred mainly in cases done early in the series.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582681 TI - [Parkinsonism, depression and akathisia induced by flunarizine, a calcium entry blockade--report of 31 cases]. AB - Flunarizine hydrochloride (FZ), a calcium entry blockade, has been used nationwide in Japan as a cerebral active vasodilator since October, 1984. The present paper reports 31 cases of FZ-induced Parkinsonism, depression and akathisia, referred to our hospital between October 1986 and September 1988. Out of the 31 patients, four including two with Parkinson's disease and one each with progressive supranuclear palsy and olivopontocerebellar atrophy showed worsening of their parkinsonian symptoms within a few months after FZ administration. The remaining 27 patients (7 males and 20 females) newly developed Parkinsonism after treatment with FZ. Symptoms appeared one week to two years (mean: 6.1 months) after starting FZ of a daily dose of 10 mg. FZ had been used in 6 patients for cerebrovascular episodes confirmed by clinical history or brain CT, and in the remainder, for dizziness, light-headedness, hypertension, amnesia or hypochondric neurotic complaints. Akinesia and bradykinesia progressed rather rapidly after onset, and patients became unambulatory within several months. Symptoms had worsened, and L-dopa, anticholinergic drugs, and bromocriptine had been ineffective until FZ was discontinued. Their Parkinsonism was characterized by marked akinesia, bradykinesia, and moderate rigidity. Masked face was seen in most of them. Tremor was absent at rest, and induced in 12 patients by posture and/or action. Sixteen patients were accompanied by depression, and five, by akathisia. Improvement began several weeks after withdrawal of FZ, and most patients recovered almost completely within a few months although mild rigidity and bradykinesia remained in some.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582680 TI - A new system to produce intraoperatively custom femoral prosthesis from measurements taken during the surgical procedure. AB - A system has been developed that allows the surgeon to match a prosthesis to any femoral cavity. The surgeon may choose how and where it will preferentially fit. The surgeon does not have to create a cavity to suit a premade prosthesis. The system is based on a novel technique for making a mold of the prepared femoral cavity. This is accurately and thoroughly measured using a laser. An implant is designed and manufactured while the operation is in progress using state-of-the art computer and machining techniques. All important parameters such as neck length, offset, and anteversion are fully variable intraoperatively. To date, more than 800 consecutive procedures have been carried out. In a limited trial, no subjective difference was found with a cemented Charnley total hip arthroplasty at one year. It currently takes about 40 minutes to manufacture the implant and make it available in the operating room, and this time is being continually reduced. Using a femur first approach, operating time is not greatly extended. In the future, perhaps the operating time will not be extended at all. All data including cavity geometry are centrally recorded for analysis. PMID- 2582682 TI - [Adult-onset Hartnup disease presenting with neuropsychiatric symptoms but without skin lesions]. AB - Hartnup disease is an inborn abnormality of renal and intestinal transport involving the neutral amino acids. Intermittent pellagra-like rash, attacks of cerebellar ataxia and psychiatric disturbance are characteristic symptoms of this disease. We described here a patient with adult-onset Hartnup disease who presented unique neuropsychiatric symptoms but no dermatologic symptoms, and reported features of amino acids transport in this patient and his family. The patient, a man aged 37 years, was referred to us because of lasting daytime bruxism. He is the second child of healthy parents who are first cousin; his elder brother who has been mentally retarded became bed-ridden and died at 32 years of age. His younger brother is completely healthy. Although the patient's development in infancy has been slightly retarded, he completed compulsory 9-year education. At 29 years of age, he experienced episodes of diplopia, ataxic gait and insomnia, and at 33 years of age, of transient stupor. There had been no history of photosensitivity or dermatitis. On neurological examination, there were trunkal ataxia, increased muscular tone and decreased mental activity besides bruxism. These symptoms remained unchanged despite of several medications including trihexyphenidyl, diazepam, halloperidol, tiapride and sulpiride. Two months later, the patient became stuporous; bruxism and hypertonicity became exaggerated. Myerson's sign, sucking reflex and grasp reflex in both hand appeared. There was no dermal lesion. A cranial computed tomography revealed a small calcification in the right frontal subcortical region and a single photon emission tomography indicated possible bifrontal hypoperfusion. Electroencephalograms demonstrated non-specific slowing. Somatosensory evoked potentials and nerve conduction velocities were normal. There were constant indicanuria and amino-aciduria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582683 TI - [Sweating deficiency in myotonic dystrophy]. AB - We evaluated local sweating function quantitatively in nine cases of myotonic dystrophy (MyD) aged 26 to 61 years (mean, 45.4 years) and 25 control subjects aged 24 to 71 years (mean, 50.1 years). MyD subjects were grouped into three clinical classes according to their severity (three mild cases; class 1, three moderate; class 2 and three severe; class 3). 10 mg of acetylcholine was injected intradermally on the dorsum of the foot. After stimulation the impressions of sweat droplets were obtained using vinyl silicon impression material and the number of sweat droplet impressions per square centimeter was counted and the diameter of each droplet was measured by an image processor using a microcomputer. The result showed statistically significant decrease in the number of sweat droplets in class 2 and 3 as compared with control group and class 1. The histogram of sweat droplet diameter disclosed tendency of progressive deficit in diameter in all three clinical classes of MyD. Various kinds of autonomic function test, besides sweat tests, and nerve conduction study done on class 2 and 3 failed to show any significant abnormalities. Skin biopsy study done on lower leg on four subjects of class 2 and 3 revealed atrophy of eccrine sweat glands. These results suggests that local sweating deficiency develops in MyD as the disease progresses and that this deficiency is caused by dysfunction of eccrine glands, and not of postganglionic autonomic nerves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582684 TI - [Changes in free amino acids in the central nervous system of hypo- and hyperthyroid rats]. AB - The increase in the content of taurine in the central nervous system (CNS) of amyotrophic lateral sclerosis (ALS) may probably be related to the impairment of folate cycle. In addition, the appearance of pyramidal sign in patients with hyperthyroidism as well as impairment of folate metabolism in thyropathies have been reported. This study was undertaken to investigate whether excess or deficiency of thyroid hormones could induce changes in free amino acids and folate cycle in CNS. Wistar male rats weighing approximately 370 g were used. Forty rats were thyroidectomized, and twenty were sham-operated as control under pentobarbital anesthesia. After 22 to 24 weeks, these animals were sacrificed by decapitation and the blood was collected in a heparinized and a non-heparinized container. Brain, spinal cord, liver, skeletal muscle, erythrocytes, plasma, and serum were stored at -80 degrees C until analyzed. To make hyperthyroidism in rats, triiodothyronine (T3) solved in alkaline 0.9% saline (10 micrograms of T3/100 g of body weight) were injected intraperitoneally to 16 rats six times a week, totally thirty times. Only alkaline 0.9% saline were injected to sixteen controls. These rats were sacrificed by the same way described above and each material was also stored at -80 degrees C. The content of taurine was changed in various tissues including CNS in thyroidectomized and T3-injected rats. The significant increase of taurine was seen in spinal cord and skeletal muscle of thyroidectomized rats. On the other hand, the significant decrease of taurine was observed in brain, liver, and skeletal muscle of T3-injected rats. The folate level was increased only in liver of thyroidectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582685 TI - [Magnetic resonance imaging of parkinsonism]. AB - We have analyzed magnetic resonance images in 33 patients; 18 patients with Parkinson's disease, 1 patient with diurnally fluctuating progressive dystonia, 1 patient with pure akinesia, 6 patients with multiple system atrophy, 1 patient with flunarizine induced parkinsonism, and 4 patients with unclassified parkinsonism. The MR images were obtained using a 1.5-T GE MR System. A spin-echo pulse sequence was used with a TE of 30 msec and 80 msec and a TR of 2000 msec. No signal abnormalities were seen in any patient with Parkinson's disease but 3 showed slightly decreased signal intensity of the putamen on T2-weighted sequences. Patients with diurnally fluctuating progressive dystonia and pure akinesia evidenced no abnormal findings. All six patients with multiple system atrophy demonstrated decreased signal intensity of the putamen, particularly along their lateral and posterior portions, and an enlarged substantia nigra. Atrophy of the pons and cerebellum was detected in all cases with multiple system atrophy. One case of flunarizine induced parkinsonism showed slightly decreased signal intensity of the putamen. Four cases of unclassified parkinsonism showed decreased signal in the putamen on T2-weighted sequences. Magnetic resonance imaging has the potential to become a useful diagnostic tool in the management of parkinsonism. PMID- 2582686 TI - [Thermal sudomotor deficits in Parkinson's disease]. AB - In order to evaluate sympathetic functions in Parkinson's disease (PD), thermal sweating was examined with colorimetric method in 50 cases of PD (22 males & 28 females, mean age at examination: 58 +/- 9.6 ys, mean duration of illness: 5.3 +/ 3.6 years, Hoehn and Yahr's stage: II-IV, patients without drugs: 15), and following results were obtained; normal sweating in 20 (A), possible generalized hyperhidrosis in 5 (B), localized hyperhidrosis in 4 (C), unilateral hypohidrosis in 7 (D), hypohidrosis over the trunk and legs in 7 (E), and anhidrosis over the trunk and lower extremities in 7 (F). In group F, acetylcholine- or pilocarpine sweating was also defective, suggesting that postganglionic sympathetic fibers were also impaired. The results were analyzed with respect to age, duration and severity of illness, predominant somatic symptoms, postural changes of blood pressure or subjective dysuria. Abnormal sweating appeared to be related to higher age, severity of PD, and to rigid akinesia as the predominant symptoms. Group B appeared to involve relatively young patients without orthostatic hypotension or dysuria. Group B and C included 5 tremor-dominant patients. But, these features were not statistically significant. Patients in group F had rigid akinesia as the predominant feature (p less than 0.01), and showed higher incidence of dysuria (p less than 0.05). They appeared to have severe PD symptoms in spite of relatively shorter duration of the disease. An administration of drugs including anticholinergics had no significant influence upon the present results. It has been reported by several authors that the rapid progression of PD symptoms and early deterioration of mental status are related to rigid akinesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582687 TI - [Metabolic acidosis and hypoglycemia during calcium hopantenate administration- report on 5 patients]. AB - Calcium hopantenate (HOPA) has been widely used as an activator of cerebral metabolism in Japan. However, several cases of acute encephalopathy during HOPA administration were recently reported, which were characterized by marked metabolic acidosis and hypoglycemia. The encephalopathy in these patients was named Reye-like syndrome because of the similarity to Reye's syndrome in children. The purposes of this presentation are to report on 5 patients with acute encephalopathy developing during HOPA administration, to summarize their symptoms and clinical courses, and to discuss the pathogenesis of metabolic acidosis and hypoglycemia. Initial characteristics of the clinical course in all patients were loss of appetite, nausea and vomiting, followed by unconsciousness. Laboratory examinations revealed marked metabolic acidosis, severe hypoglycemia, hyperlactacidemia, leukocytosis, ketonuria, and increased Ht and BUN. A few days after development of the initial symptoms, mild renal and liver dysfunction, and elevation of serum amylase were observed in all patients. Hyperlactacidemia was present in 4 in the initial period. Blood concentration of HOPA was 2.131 micrograms/ml in patient 1 (8-10 hours after final administration), and 10.7 micrograms/ml in patient 5 (24 hours after final administration). These values are extremely high, because usually HOPA concentration is almost negligible 7 hours after the drug is taken. As the pathogenesis of acute encephalopathy due to HOPA administration, the failure of fatty acid beta-oxidation has been proposed by some investigators. However, the serum concentrations of CoA, pantothenic acid and carnitine during the initial stage were not reduced in our patients. Furthermore, it is very difficult to explain the severe hypoglycemia in terms of the beta-oxidation theory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582689 TI - [A case of acute spinal epidural hematoma with spontaneous resolution and its MRI]. AB - A case of non-traumatic spinal epidural hematoma (SEH) with spontaneous resolution was reported. A 80-year-old woman was admitted to our hospital for her paraplegia of acute onset. She had had no specific previous history, and she did not either receive any drug or suffer from hypertension. On admission, general status was unremarkable. Flaccid paralysis of lower extremities and bilateral sensory disturbance of all modalities below the level of Th4 were observed. Deep tendon reflexes were normal in upper extremities, while absent in lower extremities. Babinski's sign was not elicited. From the findings of CT and metrizamide CT myelography, SEH of ventral type was presumed. MRI revealed hematoma compressing spinal cord over two vertebral segments, and widely spreading even to C7 rostrally and to Th10 caudally. Urgent surgical intervention was taken into consideration, but was not performed because of her rapid improvement: sensory disturbance alleviated from day to day, and she became able to walk within the 3rd day of hospitalization. Almost complete recovery from motor and sensory dysfunction was achieved in about 7 days after admission. Only 4 cases of spontaneous recovery of SEH have been reported so far, and this patient is the 5th such case. Although CT and metrizamide CT myelography are useful in diagnosing SEH, MRI is also proved to be an accurate and efficacious method for evaluation of its size, location and extent in the spinal canal. PMID- 2582688 TI - [A case of ischemic oculopathy followed by border zone infarction]. AB - We reported a 72-year-old male with ischemic oculopathy due to ophthalmic artery stenosis followed by ipsilateral border zone infarction due to internal carotid artery stenosis. The patient had history of hypertension and diabetes mellitus. He had severe headache and visual disturbance of the right eye. He was diagnosed right neovascular glaucoma and left diabetic retinopathy (simple type), and received diuretics, beta-blockade and other anti-hypertensive drugs. One month later, he noticed left mild hemiparesis in a morning, and he experienced progression of left hemiparesis over a week. He was admitted to our hospital on the 11th day. He showed left complete hemiplegia, left sensory disturbance, anosognosia and left unilateral spatial neglect. His right eye was diagnosed neovascular glaucoma but left eye was normal. The 5th days CT showed low density area in the right terminal zone and bilateral periventricular lucency. At the same area, the 46th days MRI showed high intensity area in the T2-weighted image and low intensity area in the T1-weighted image. Cerebral angiography performed on the 33rd day, disclosed severe kinking at the cervical segment and 50% stenosis at the intracavernous segment in the right internal carotid artery, and 90% stenosis and post-stenotic dilatation of the right ophthalmic artery. Left internal carotid artery had each 60% stenosis at the cervical segment and the intracavernous segment. Left ophthalmic artery had severe stenosis from its beginning to distal part. This infarction was considered berder zone infarction by it's localization (terminal zone) and internal carotid artery stenosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582690 TI - [A case of malignant rheumatoid arthritis with severe peripheral neuropathy]. AB - A 72-year-old woman of definite type of malignant rheumatoid arthritis (MRA) with severe peripheral neuropathy. She has often noted pain of both shoulders or knee joints since some years ago. At the age of 71, she noticed numbness of the feet with pain and swelling of knee joints. She was diagnosed as definite type of rheumatoid arthritis by one podiatrist. Although she took some medications, she subsequently developed general fatigue, appetite loss, exacerbation of arthritis, drop feet and hands with prominent coldness. She was admitted to our hospital on March 22, 1985. On examination, she revealed purpura, decubitis, heart murmur, arthritis of knee joints, and fingers necrosis with skin ulcer. She had severe muscle weakness, and wasting of four limbs. Moderate impairment of all-modality sensations were noted in all extremities. Distal involvement was greater than proximal. Laboratory data during administration of prednisolone (60 mg/day) were as follows: glucose in urine, 2+; occult blood in urine, 1+; white blood cells count, 18600 with 92% polymorphonuclear leukocytes; erythrocyte sedimentation rate, 60 mm in an hour; CRP, 14.62 mg/dl (normal 0.5 greater than); RA test, 2+; RAHA, 10240; CH50, 10 U/ml (normal 32-42); C3, 37 mg/dl (normal 55-75); C4, 9 mg/dl (normal 15-28); immune complex, 4.4 micrograms/ml (normal 3.0): Chest X-ray film showed cardiomegaly (CTR, 57%). ECG disclosed atrial premature contraction, and echo cardiography suggested epicarditis with aortic valve insufficiency. 99mTc RI angiogram revealed impairment of peripheral circulation. SCV on sural nerve was not elicited. Sural nerve biopsy showed obliterans type of endoarteritis and axonal degeneration with loss of myelinated fiber. PMID- 2582691 TI - [A case of Burkitt's lymphoma with numb chin syndrome as the initial manifestation]. AB - In 1963, Calverley and Mohnac reported four cases with sensory disturbance of the mental nerve region. They emphasized the symptomatological significance of that finding because of the underlying ominous diseases. The purpose of this paper is to emphasize the clinical importance of this symptom especially as the initial manifestation of the underlying malignant diseases. A 56-year-old Japanese female was seen in consultation because of complaints of the paresthesia over the distribution of the right mental nerve, diplopia and ptosis of the right side. The patient had been well until a hundred days prior to admission, when she noted numbness with pain of the right mental nerve region. This symptom was followed by ptosis of the right side and diplopia after five weeks. MRI-CT scan revealed an abnormally low intensity echo (in T1 weighted image) of the bone around sphenoid sinus and tumor of the cavernous sinus (in T2 weighted image) compressing the right internal carotid artery. The patient was transferred to this hospital 100 days after the occurrence of the initial symptom. Physical examination revealed neither superficial lymph node swelling nor buccal tumor. Abnormal findings were restricted to the cranial nerve regions such as diplopia, adduction disturbance, sluggish light reflex of the right side and hypesthesia on the right chin, lower lip and buccal mucous membrane. Other neurological findings were not significant. Laboratory findings showed elevated LDH (1,503 IU/L). Leucocyte cell count was 7,500/mm3 with almost normal composition. CSF was normal. A diagnosis of Burkitt's lymphoma stage IV was done by nasopharynx and bone marrow biopsies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582692 TI - [Autonomic dysfunctions in acute intermittent porphyria]. AB - A young woman with acute intermittent porphyria is described. She was admitted in a prolonged attack and had developed a flaccid quadriplegia. During the course she showed various manifestations of the autonomic nervous system, including pupils, gastrointestinal tract, cardiovascular system and others. On admission her pupils were equally mydriatic, and reacted to light sluggishly. Dilation of the pupils was seen when cocaine was instilled, but not when adrenalin. It was suggested that the parasympathetic control of pupils was disturbed. She complained repeatedly abdominal pain, nausea, vomiting, and constipation. However, diarrhea was rarely found. Radiological examinations revealed that her bowel movements were markedly impaired. Sinus tachycardia and elevation of blood pressure were frequently observed with attacks, and they correlated with the clinical course. With tachycardia the coefficient variance of R-R interval was markedly decreased, and large dose of atropine failed to accelerate the heart rate. These indicate that the vagal function was markedly impaired with attacks. The effects of isoproterenol and of propranolol on the heart rate were normal. Phenylephrine and phentolamine changed the blood pressure normally. From these it was concluded that the sympathetic nervous function was not so impaired at the time examined. However, with the elevation of blood pressure plasma and urinary noradrenaline were markedly increased. Other autonomic and related manifestations observed during the course included disorders of sweating, loss of sphincter control, fever of unknown cause and amenorrhea. PMID- 2582693 TI - [A case of sarcoidosis presenting ataxic hemiparesis as an initial clinical manifestation]. AB - A case of sarcoidosis presenting ataxic hemiparesis was reported. A 25-year-old man was admitted to Kanto Teishin Hospital because of slight weakness and dysesthesia in the right side of his body. His physical findings were normal. Neurological findings disclosed mild right hemiparesis (MMT 4+), cerebellar signs and mild dysesthesia in the same side. Laboratory findings were within normal limits except for elevated serum ACE and lysozyme. Chest roentgenogram showed bilateral hilar lymphadenopathy and TBLB disclosed sarcoid granuloma. Though brain CT, brain MRI and cerebral angiography were within normal limits, the neurological features were thought to be due to sarcoidosis. They disappeared along with the decrease of ACE and lysozyme. This is the first report of ataxic hemiparesis due to sarcoidosis, and it is interesting in that ataxic hemiparesis, which is one of signs of diseases in central nervous system, is the first manifest clinical feature of sarcoidosis. PMID- 2582694 TI - Pharmacokinetics of sulpiride after intravenous administration in patients with impaired renal function. AB - Single intravenous doses of sulpiride 100 mg were administered to 18 patients with renal function impairment, and 6 healthy volunteers. The plasma concentration-time profile is described by a 2-compartment open model. The differences between the pharmacokinetic parameters of sulpiride for the 2 groups were statistically significant. Elimination half-life, mean residence time and area under the plasma concentration-time curve are significantly greater in renal failure; renal and total clearance, and the cumulative amount of unchanged sulpiride in urine, are significantly reduced but volume of distribution remains unchanged. Creatinine clearance was strongly correlated with renal clearance of sulpiride, elimination rate constant, area under the curve and cumulative amount excreted in urine. For patients with impaired or physiologically reduced renal function receiving long term sulpiride treatment, a 35 to 70% reduction in dose, or extension of the dosage interval by a factor of 1.5 to 3, may be required. PMID- 2582695 TI - Adolescent cocaine abuse. Addictive potential, behavioral and psychiatric effects. AB - Four hundred seventy-nine drug abusing adolescent patients enrolled in seven Straight, Inc. Adolescent Drug-Abuse Treatment Programs in five geographic regions across the United States were studied to determine the severity and patterns of cocaine abuse. Of these, 341 admitted to cocaine use and became part of this survey. Cocaine use was categorized as heavy, intermediate, or light. Areas examined were the addictive spectrum, psychosocial dysfunction, and psychiatric symptoms. Intermediate and heavy users of cocaine abused significantly less marijuana and inhalants than light cocaine abusers. Heavy and intermediate users were more likely to use cocaine intravenously and to use crack. They developed tachyphylaxis more frequently, progressed to weekly use in less than 3 months more frequently, and became preoccupied with obtaining and using cocaine significantly more frequently. They used more sedative hypnotics to calm themselves and engaged in more criminal behavior, such as stealing from parents and stores and passing bad checks. They had more arrests for possession of drugs, stole more cars, sold more drugs, and were more likely to trade sexual favors to obtain the drug. Heavy and intermediate users were significantly more psychiatrically disturbed than light users, becoming more suspicious, nervous, aggressive, and demonstrating increased symptoms of fatigue, sleeplessness, decreased appetite, and increasing cocaine dysphoria. All of these symptoms could be mistaken for psychiatric disorders. This study suggests that cocaine is as addictive in adolescents as in adults; possibly more so. It also causes psychosocial dysfunction and psychiatric symptoms. Further research into cocaine addiction among adolescents is indicated. PMID- 2582696 TI - Atypical anorexia nervosa and hysterical symptomatology in a child with acute lymphocytic leukemia. A case management conference. PMID- 2582697 TI - Thyroid storm. Presenting with coma and seizures. In a 3-year-old girl. AB - Thyroid storm is a rare occurrence in the adult population and is even more unusual in children. The current report is of a 3.5-year-old girl who had thyroid storm with unique neurologic manifestations, namely seizure and coma. Acute medical management with propylthiouracil, saturated solution of potassium iodide, hydrocortisone, and propranolol brought about complete resolution of symptoms. PMID- 2582698 TI - Congenital hypopituitarism. With free water intolerance and lack of thymic involution. Early recognition of clinical presentation. PMID- 2582699 TI - Catheter-induced aortic thrombus masquerading as coarctation of the aorta. AB - The placement of an umbilical artery catheter is firmly established as an essential technique in the care of ill neonates. This simple procedure involves well recognized risks. Thrombotic complications are frequently seen with umbilical artery catheter (UAC) placement. The occurrence, however, of an aortic thrombus presenting as classical aortic coarctation has not been reported previously. This report describes two infants with classical symptomatology of coarctation of the aorta who were found instead to have aortic thrombus formation in association with umbilical artery catheter placement. PMID- 2582700 TI - Neonatal hematemesis: use of red blood cell antigens to differentiate maternal from fetal blood. PMID- 2582701 TI - Dorsal penile nerve block for circumcision. PMID- 2582702 TI - Umbilical cord care. PMID- 2582703 TI - Tobacco ingestions in children. PMID- 2582704 TI - Clinical pharmacology comes of age. PMID- 2582705 TI - The state of pediatric clinical pharmacology: an international survey of training programs. PMID- 2582706 TI - Alteration of zidovudine pharmacokinetics by probenecid in patients with AIDS or AIDS-related complex. AB - The anti-human immunodeficiency virus drug zidovudine is metabolized extensively in human beings to the 5'-glucuronide (GAZT) and is cleared rapidly, resulting in a short half-life and the need for frequent dosing. This study explores whether probenecid, which is also metabolized by glucuronidation, reduces zidovudine clearance when zidovudine is administered orally to patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). The mean zidovudine plasma levels were significantly higher after concurrent administration of probenecid than in its absence, resulting in a twofold increase in the mean AUC, a corresponding decline in the apparent total clearance, and a prolongation in the mean half-life. Similar alterations were observed in GAZT disposition. There was a marked reduction in the urinary excretion ratio of GAZT to zidovudine and a decline in the renal clearance of GAZT after probenecid coadministration. Probenecid inhibits zidovudine glucuronidation and renal excretion of GAZT. PMID- 2582708 TI - Fasting plasma homocysteine as a sensitive parameter of antifolate effect: a study of psoriasis patients receiving low-dose methotrexate treatment. AB - We have investigated the effect of low-dose methotrexate (25 mg weekly) on plasma homocysteine in 13 patients who had psoriasis. Total, free, and protein-bound homocysteine were determined both during fasting and after methionine loading. Psoriasis patients had significantly higher basal plasma homocysteine levels than age-matched control subjects. In addition, the methionine loading test was abnormal in four of the patients, but this was not significant. Psoriasis patients, although not folate deficient, did have lower serum folate levels than control subjects. There was a significant and transient increase in fasting plasma homocysteine levels within 48 hours after administration of low-dose methotrexate. This response was repeated after each administration and was observed eight to 20 times in three patients whose progress was monitored for 2 to 6 months. Notably, methotrexate did not affect the plasma profile for homocysteine after methionine loading. This study showed the level of fasting plasma homocysteine to be a sensitive and responsive parameter of antifolate drug treatment. PMID- 2582707 TI - Sulfation pharmacogenetics: correlation of human platelet and small intestinal phenol sulfotransferase. AB - Phenol sulfotransferase (PST) catalyzes the sulfate conjugation of phenolic drugs. All human tissues studied contain a thermostable (TS) form of PST, which catalyzes the sulfate conjugation of "simple" phenols such as p-nitrophenol, and a thermolabile (TL) form, which catalyzes the sulfation of dopamine and other monoamines. In the present study we tested the hypothesis that genetically controlled levels of TS and TL PST activity in the platelet, as well as inherited variations in the thermal stability of platelet TS PST, might reflect those same characteristics of the enzyme in the less accessible tissue, human small intestinal mucosa. Platelet TS and TL PST activities and TS PST thermal stability were measured in blood samples from 45 randomly selected healthy subjects, and 14 of those subjects were selected to have intestinal biopsies performed. There was a significant correlation between levels of platelet and jejunal mucosal TS PST activity (rs = 0.574, p less than 0.030), but there was not a significant correlation between levels of TL PST activity in the two tissues (rs = 0.265, p = 0.368). There was also a significant correlation between the trait of TS PST thermal stability in the two tissues (rs = 0.828, p less than 0.0001). These observations suggest that inherited variations in TS PST activity and thermal stability in an easily obtained tissue, the platelet, might be used to predict individual differences of those properties of the enzyme in the human small intestine, an organ that plays an important role in drug metabolism. PMID- 2582709 TI - Lidocaine metabolism in human liver microsomes by cytochrome P450IIIA4. AB - The metabolism of lidocaine to its major metabolite monoethylglycinexylidide (MEGX) was studied in human liver microsomes of 13 kidney transplant donors and of one patient with liver cirrhosis. Interindividual variation in metabolite formation was considerable. Biphasic kinetics indicated the involvement of at least two distinct enzymatic activities. With use of a series of antisera that recognize different human cytochrome P450 isozymes, we were able to identify an enzyme of the P450III gene family as one of two enzymes. By expressing human P450IIIA4 complementary deoxyribonucleic acid (cDNA) in HepG2 cells, we directly demonstrated lidocaine-deethylase activity for this P450 isozyme. These data suggest that P450IIIA4 is at least in part responsible for microsomal MEGX formation. PMID- 2582710 TI - Decreased plasma albumin concentration results in increased volume of distribution and decreased elimination of midazolam in intensive care patients. AB - The pharmacokinetic parameters of 16 patients in the intensive care unit, sedated with midazolam, were evaluated. A large variation was observed in the plasma concentration of midazolam and between the plasma concentration of midazolam and its metabolite 1-hydroxymethylmidazolam glucuronide. The plasma albumin concentration governs the volume of distribution of midazolam. Decreased plasma albumin concentration (25 gm/L) results in an increased volume of distribution and a decreased elimination rate of midazolam. The observed plasma concentration ratio between the parent drug and its metabolite 1-hydroxymethylmidazolam glucuronide is governed by the variables of protein binding, the metabolic rate of midazolam, and the renal clearance of the glucuronide metabolite itself (which can be considered as a measure of the kidney function of the patient). PMID- 2582712 TI - Lack of effect of cimetidine on acetaminophen disposition in humans. AB - The effect of cimetidine administration on the disposition of acetaminophen was evaluated in seven men and six women. One gram of acetaminophen was administered to each volunteer after an overnight fast on two occasions in a balanced crossover design with and without cimetidine, 300 mg every 6 hours beginning 50 hours before acetaminophen administration and continuing for 22 hours after. N Acetylcysteine was administered on both occasions when acetaminophen was ingested to protect against glutathione depletion. Blood samples were collected serially for 12 hours after acetaminophen administration, and total urine volume was collected for 24 hours. Fractional clearances of acetaminophen through renal and metabolic routes (sulfation, glucuronidation, 3-hydroxylation, and glutathione conjugate formation) were not altered by cimetidine administration. Studies in microsomes prepared from two human organ donors indicated that cimetidine inhibited acetaminophen reactive metabolite formation noncompetitively, with Ki values of 0.35 mmol/L and 0.32 mmol/L for the respective livers, which is 5 to 10 times the putative cimetidine concentration required for therapeutic effect. PMID- 2582711 TI - Pharmacodynamics of intravenous ranitidine after bolus and continuous infusion in patients with healed duodenal ulcers. AB - Fifteen adult men who had histories of duodenal ulcer disease were studied for 24 hours during treatment with varying intravenous doses of ranitidine (50 mg every 8 hours, 100 mg every 12 hours, 6.25 mg/hr continuous infusion, and 10 mg/hr continuous infusion) and placebo. Gastric pH was monitored under fasting conditions by means of an indwelling pH sensitive electrode. The continuous infusion regimens provided the most constant level of acid suppression. A "breakthrough" decrease in gastric pH began at approximately 6 PM at the 6.25 mg/hr dose level. The drop in pH at the 10 mg/hr dose level was less impressive. Ranitidine, 100 mg every 12 hours, resulted in better acid suppression than the regimen of 50 mg every 8 hours. A gastric pH greater than or equal to 4 was achieved 35 to 50 minutes after the start of administration for all regimens. The median effective concentration (EC50) of ranitidine was approximately 45 ng/ml. Continuous infusion regimens, with a dosage adjustment for the time of day, may be the optimal dosage regimen for patients requiring continuous protection from gastric damage by hydrochloric acid. Bolus loading doses are not required to speed the onset of effect in the clinical setting. PMID- 2582713 TI - Publish? Perish the thought! PMID- 2582714 TI - Evidence of HLA-linked susceptibility gene(s) in respiratory distress syndrome. AB - In a prospective study 101 newborns were enrolled into four groups: Group I included 38 unrelated newborns suffering from RDS and four sets of twin sibs (seven of whom had RDS; Group II included prematures free from RDS and any other disease; Group III included 21 newborns) delivered by C.S. and free from RDS and any other disease; Group IV included 20 infants of diabetic mothers free from RDS. HLA antigens were typed for all the newborns. The analysis of results could be summarized as follows. (1) Strong association between A3 antigen (RR = 19.4, WY2 = 59.8, S = 0.599) and B14 antigen (RR = 14.1, WY2 = 50.7, S = 0.489) and RDS. (2) HLA haplotypes were identical in twins sibs suffering from RDS and nonidentical in twins when one sib had RDS and the other is free. (3) The frequencies of A3 and B14 among the other three groups were insignificantly different from the general population and highly significantly low compared to RDS group. In conclusion, the development of RDS depends probably on the presence of susceptibility gene(s) in linkage disequilibrium with A3 and B14 antigens. Environmental factors, magnified by prematurity, in such susceptible newborns affect the production of surfactant leading to the development of RDS. PMID- 2582715 TI - Breast cancer and the MNSs blood groups. AB - Breast cancer has been reported to be associated with the Ss blood group system and specifically the ss blood genotype. This report was not substantiated by further work which concluded that the difference between the two studies may have been due to different aetiological factors in the two groups of patients studied. Breast cancer has a familial element so we decided to study the Ss and MN blood groups in familial and sporadic breast cancer patients and normal women with a positive family history along with a control group. We observed an increased incidence of the SS blood genotype in familial, sporadic breast cancer patients and women at an increased risk of developing breast cancer compared with a control group. PMID- 2582717 TI - HIV/HTLV gene nomenclature. PMID- 2582716 TI - Detection of HIV-1 RNA sequences by in vitro DNA amplification. PMID- 2582718 TI - Location and chemical synthesis of a binding site for HIV-1 on the CD4 [correction of CE4] protein. PMID- 2582719 TI - Effect of aluminium on superoxide dismutase. AB - 1. The effect of Al3+ on superoxide dismutase in vitro was studied, since in uraemia there is excessive superoxide production and frequently an elevated serum Al3+ level. Thus, the protective role of superoxide dismutase is particularly important. 2. Al3+ in concentrations similar to those found in the serum of uraemic patients inhibits superoxide dismutase activity. The degree of inhibition is directly proportional to the Al3+ level. 3. The combination of excessive oxygen free radical production with an increased Al3+ level may contribute to a variety of complications, including aluminium dementia or initiation and promotion of carcinogenic processes, which are known to be more common in uraemic patients. PMID- 2582720 TI - Effect of vasopressin on bronchial reactivity to histamine. AB - 1. Recent evidence suggests that a high salt diet increases bronchial reactivity, but the underlying mechanism is unclear. 2. To determine whether alterations in circulating vasopressin might be responsible, we have studied the effect of an infusion of vasopressin on the airways of six normal and eight asthmatic subjects measuring the response as expiratory flow at 30% of vital capacity (V30P) in the normal subjects and as forced expiratory volume in 1s (FEV1) in the asthmatic subjects, in a double-blind, placebo-controlled, cross-over study. 3. Vasopressin, given as an infusion at a rate of 2 i.u./h for 1 h, followed by 4 i.u./h for a further hour, produced plasma concentrations of 12.8 and 17 ng/l, respectively, compared with 2.0 and 2.0 ng/l on placebo. 4. Airway reactivity to histamine was measured after 1 and 2 h as the provocative doses of histamine causing a 40% reduction in V30P (PD40V30P) in the normal subjects and a 20% reduction in FEV1 (PD20FEV1) in the asthmatic subjects. 5. There was a small increase in PD40V30P after both vasopressin and placebo in normal subjects (refractoriness) but no change in PD20FEV1 in the asthmatic subjects. 6. There was no significant difference between vasopressin and placebo in V30P or PD40V30P over the 2 h after the drug in the normal subjects or in FEV1 or PD20FEV1 over the 2 h after the drug in the asthmatic subjects. 7. We conclude that alterations in circulating vasopressin are unlikely to be responsible for the increase in bronchial reactivity when dietary salt intake is increased. PMID- 2582721 TI - Reduced selenium status of patients with asthma. AB - 1. Selenium is an essential component of glutathione peroxidase (GSH-Px, EC 1.11.1.9), an enzyme which helps protects cells against damage caused by free radicals and hydroperoxides. 2. We report the plasma, whole blood and platelet concentrations of selenium, and whole blood and platelet activities of GSH-Px, in 49 patients with asthma, 23 of whom had coexisting eczema, and 76 healthy control subjects. 3. The asthmatic patients had significantly lower concentrations of selenium measured in plasma (P less than 0.001) and whole blood (P less than 0.001), but not in platelets. When the data were summarized as odds ratios there was a highly significant 3.54- and 5.08-fold increased probability of asthma observed for the lower range of plasma and whole blood selenium concentrations, respectively. 4. No overall decrease in platelet or whole blood GSH-Px activity was found when the asthmatic and control groups were compared. 5. Although patients with symptomatic asthma have a reduced selenium status, this does not appear to influence the antioxidant capacity of their circulating blood cells. PMID- 2582722 TI - Effect of ligustrazine on pulmonary vascular changes induced by chronic hypoxia in rats. AB - 1. Acute and chronic effects on the pulmonary circulation of ligustrazine, a chemically identified and synthesized principle of a Chinese herb, were studied in rats. It dilated lung vessels and reversed hypoxic pulmonary vasoconstriction. 2. In rats kept 2 weeks in 10% O2 in a normobaric chamber and simultaneously treated with ligustrazine, right ventricular hypertrophy and muscularization of pulmonary arterioles were attenuated compared with saline-treated rats. Pulmonary artery pressure, measured in isolated lungs perfused at a constant flow rate, was also less in ligustrazine-treated rats. 3. In isolated blood-perfused lungs of chronically hypoxic and control rats, the relation between pressure and flow was measured during normoxia (ventilation with air plus 5% CO2), hypoxia (2% O2 plus 5% CO2) and after ligustrazine during continued hypoxia. Alveolar pressure was always greater than left atrial pressure; thus flow was determined by the pulmonary artery minus alveolar pressure difference. 4. Pressure/flow lines were measured during normoxia in four groups of rats: (1) control, saline-treated; (2) control, ligustrazine-treated; (3) chronically hypoxic, saline-treated; (4) chronically hypoxic, ligustrazine-treated. Both chronically hypoxic groups had steeper lines (higher resistance) than the control groups, which were similar in all respects. However, in chronically hypoxic rats, the extrapolated intercept of the line on the pressure axis, probably attributable to small newly muscularized arterioles in a state of tone, was much increased in the saline-treated group but did not differ from controls in the ligustrazine-treated group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582723 TI - Genetic factors in the development of nephropathy in diabetic Lewis and DA rats. AB - 1. Streptozotocin was used to induce diabetes in two inbred strains of rats, Lewis and DA, known to have different glomerular properties. 2. Dietary protein intake, weight and plasma glucose were monitored during the course of the experiment, and, at regular intervals, urine collections were made utilizing metabolic cages. 3. No significant differences were found in protein intake or plasma glucose between the two strains. 4. Proteinuria was higher in the diabetic Lewis rats than in the diabetic DA rats, and the difference became progressively greater with the passage of time. After 6 months of diabetes, the median values for proteinuria were 19.9 mg/24 h in the Lewis rats and 9.0 mg/24 h in the DA rats. 5. Electron microscopic examination revealed a greater degree of mesangial expansion in the glomeruli of the Lewis rats than in those of the DA rats after 6 months of diabetes. The median fractional mesangial area was 44.8% in the diabetic Lewis rats and 31.4% in the diabetic DA rats. 6. These results suggest that Lewis rats possess an inherited susceptibility to diabetic nephropathy, and that DA rats are relatively resistant. These differences in susceptibilities support the hypothesis that inherited glomerular properties determine an individual's susceptibility to diabetic nephropathy. PMID- 2582724 TI - Haemodynamic and cerebrovascular responses to glycerol infusion in dogs. AB - 1. The response of cerebral blood vessels to hyperosmolar agents in vivo remains controversial, and little is known about the effect of glycerol on cerebral vessels. In this study we investigated the cerebrovascular response to intravenous administration of glycerol (1 g/kg, infused over 25 min) in dogs under pentobarbital anaesthesia. 2. intracranial pressure, systemic arterial pressure, mean arterial blood pressure, serum osmolarity and packed cell volume were continuously monitored, and blood gases were checked frequently. Through a parietal cranial window, pial vessel diameter was measured by means of a surgical microscope and a video image-analyser. 3. Pial vessel diameter increased gradually with a maximum at 30 min after the beginning of glycerol infusion. The maximum increase in diameter in small (less than or equal to 100 microns) vessels was 14.3%, whereas that in large (greater than 100 microns) vessels was 10.3%. There was only a slight increase (less than 4%) in pial vessel diameter in vehicle-infused animals. The intracranial pressure decreased drastically after glycerol infusion, whereas the mean arterial blood pressure remained constant. There were correlations between the rise in serum osmolarity, fall in packed cell volume and vasodilatation, indicating that glycerol caused vasodilatation accompanied by plasma volume expansion. 4. Our data suggest that glycerol produces cerebral vasodilatation, which might be beneficial in cerebral ischaemia and vasospasm, in addition to its intracranial pressure-reducing effect on normal or oedematous brain. The degree of vasodilatation was not sufficient to affect the predominant intracranial pressure drop resulting from cerebral dehydration. PMID- 2582725 TI - Sympathetic vasoconstriction as a mechanism of action of ouabain in forearm arterioles of hypertensive patients. AB - 1. The interaction of ouabain, a Na+/K+ adenosine 5'-triphosphatase inhibitor, with sympathetic mechanisms of vasoconstriction, as well as its possible site(s) of action, were investigated in forearm arterioles of patients with uncomplicated hypertension. 2. Intra-arterial infusion of ouabain per se decreased forearm blood flow without changes in systemic arterial pressure or contralateral flow. However, the vasoconstrictor effect of the glycoside was abolished after local pretreatment with either phentolamine, a competitive alpha-adrenoceptor antagonist, or bretylium tosylate, a neurotransmitter blocker. 3. To exclude a non-specific effect due to the vasodilatation, a similar protocol was performed using histamine, which acts independently of sympathetic mechanisms. The vascular effect of ouabain was maintained in spite of histamine-induced increases in forearm blood flow even greater than those obtained from either blocker. 4. To discriminate between pre- and post-synaptic site(s) of action of ouabain, exogenous noradrenaline was infused intra-arterially after inactivation of local neurotransmitter release by bretylium, thus causing direct postsynaptic vascular alpha-adrenoceptor stimulation. Under these conditions, noradrenaline decreased forearm blood flow irrespective of the presence or absence of ouabain. 5. Thus, local sympatholysis by drugs acting on different levels of the sympathetic neuroeffector junction abolished the effect of ouabain, whereas histamine did not influence it. The data provide positive evidence for an effect of ouabain on sympathetically mediated vasoconstriction. This action is apparently not exerted at a postsynaptic site but possibly by enhancing neurotransmitter release. 6. If a circulating endogenous ouabain-like Na+/K+ adenosine 5'-triphosphatase inhibitor is relevant to the development of hypertension in man, it might act through a similar mechanism. PMID- 2582726 TI - Cardiovascular reflex responses in patients with unexplained syncope. AB - 1. This study was undertaken to determine whether, in a group of patients complaining of recurrent syncopal attacks but with no apparent cause, there was evidence of abnormal cardiovascular reflex control. 2. The steady-state responses of blood pressure, heart rate and cardiac output to head-up tilting were determined in 67 patients using entirely 'non-invasive' methods. In some patients we also studied the immediate response of pulse interval to carotid baroreceptor stimulation by neck suction. 3. Two of the patients developed vasovagal attacks during the 20 min test period of head-up tilting. Eighteen others showed postural hypotension, defined as a fall in blood pressure to outside the limits of two SDS from the mean values of age-related control subjects. 4. Patients who showed postural hypotension had a mean fall in cardiac output significantly larger than that in age-related control subjects. Responses in the nonhypotensive patients did not differ significantly from controls. 5. Stimulation of carotid baroreceptors resulted in significantly smaller responses of pulse interval in the patients defined as having postural hypotension compared with the non hypotensive patients and with the age-related control subjects. 6. In some of the patients who did not show postural hypotension during the standard test, the duration of tilt was prolonged for up to 1 h. Five out of 26 patients developed vasovagal attacks. All the vasovagal patients showed an initial tachycardia and the response of pulse interval to neck suction was significantly larger than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582727 TI - Trophic effect of Efamol on the rat small-intestinal mucosa. AB - 1. The hypothesis that triacylglycerols are trophic to the small-intestinal mucosa of the rat was tested by comparing the action of the essential fatty acid rich oil Efamol with that of glucose. 2. Two groups of nine female Wistar rats were pair-fed Vivonex HN with 50% calorie substitution by glucose or Efamol for 21 days. 3. Body weight gain was greater with glucose than with Efamol, but, despite this, whole gut weight, mucosal weight and mucosal protein were increased by Efamol in all small-intestinal segments. Total mucosal DNA was also increased with a significant change in the middle small-intestinal segment. These changes were associated with an increased crypt cell production rate. 4. Fasting plasma levels of peptidyltyrosyltyrosine ('peptide YY'), but not of enteroglucagon, were significantly elevated in the Efamol-fed group. 5. The data show a trophic effect of Efamol on the rat small-intestinal mucosa. Possible mechanisms are discussed. PMID- 2582728 TI - Plasma levels of the lyso-derivative of platelet-activating factor in acute severe systemic illness. AB - 1. Evidence suggests that activation of phospholipase A2 and production of eicosanoids and platelet-activating factor (PAF) are involved in various responses associated with severe tissue damage and shock. It was postulated that the plasma level of the precursor and degradation product of PAF, lyso-platelet activating factor (lyso-PAF), might be increased in acute severe illness. 2. After plasma extraction, lyso-PAF was acetylated in vitro to PAF, which was measured by bioassay using 5-[14C]hydroxytryptamine-labelled rabbit platelets. Measurements were made in 18 severely ill patients (five with cardiogenic shock; five with severe infection, five after repair of abdominal aortic aneurysm, two with acute pancreatitis; 13 males, five females). Plasma lyso-PAF in these patients was 33 +/- 15 (SD)ng/ml (range 5-111 ng/ml), whereas values in normal males (40-65 years) ranged from 102 to 253 ng/ml (n = 15) and in females from 74 to 174 ng/ml (n = 10). Depression of plasma lyso-PAF did not relate closely to the patient group nor to specific therapy, but repeated measurements in each of 10 patients showed an increase in plasma lyso-PAF (P less than 0.002), associated with clinical improvement. 3. Evidence was obtained indicating that neither the presence of an inhibitor in the assay system nor reconversion of PAF to lyso-PAF in vitro produced the unexpected depression of plasma lyso-PAF. 4. The mechanisms responsible, which may have therapeutic implications, remain to be elucidated. PMID- 2582729 TI - Cardiac repolarization properties during standardized exercise test as studied by QT, QT peak and terminated T-wave intervals. AB - Changes in QT, QT peak (QTp) and terminal T-wave, Tp-Te (QT-QTp) were studied in 11 apparently healthy subjects during and after a standardized exercise test. ECG was recorded at scalar lead positions. Averaged complexes were later analysed by computer for the different time intervals. QT and QTp decreased in parallel with increasing heart rate with a ratio QTp/QT of 0.80 +/- 0.02 at rest and 0.74 +/- 0.02 at maximal heart rate around 170. After exercise QT and QTp prolonged disproportionately slower than heart rate, reaching the relation observed during exercise only 9.5 min post exercise. Tp-Te was 75 +/- 10 ms at rest and 65 +/- 8 ms at maximal heart rate. The decrease was significant (P less than 0.001). The main part of the rate-associated shortening of the QT interval occurred in the QTp interval where it was about six to seven times larger than in the Tp-Te interval. In conclusion, QT and QTp decreased similarly with heart rate during exercise. Post exercise there was an initial slower return of these intervals to the resting state than for heart rate. Tp-Te changes were minimal. PMID- 2582731 TI - Chest pain and oesophageal pressure relationships in man following an intravenous bolus of adenosine. AB - After titration of maximum tolerable i.v. bolus dose of adenosine, this dose was given to seven volunteers (20-42 years), instrumented with a three-lumen oesophageal pressure catheter with recording sites at the levels of the stomach, the lower oesophageal sphincter (LOS) and the oesophagus. In addition to continuous pressure recordings, chest pain was estimated continuously by a 10 graded category-ratio scale. Baseline resting pressures were 8.4 (1.9) mmHg in the stomach, 1.6 (1.7) mmHg in the oesophagus and 20 (2.6) mmHg in the LOS resulting in a net LOS pressure of 11 (+/- 1.3) mmHg. Following injection of adenosine which provoked transient chest pain with a rated maximum of 5.4 (1.0), resting oesophageal pressure did not change while net LOS pressure decreased to 1.3 (1.9) mmHg (P less than 0.0001). Adenosine injection did not affect swallowing-induced peristaltic contractions of the oesophagus and LOS although the peristaltic wave was delayed (P less than 0.05). Thus, chest pain evoked by adenosine cannot be caused by spastic oesophageal contractions. Adenosine may have a relaxing effect on the LOS but does not block its normal reactions to swallowing. PMID- 2582730 TI - Cardiovascular and metabolic response to adrenaline infusion in weight-losing patients with and without cancer. AB - Fasting is generally accompanied by a decrease in energy metabolism and hormones. On the other hand, indirect evidence has suggested that the response to adrenergic agonists may be maintained or even increased in malnutrition. The present study evaluated whether weight-losing patients with and without cancer have increased plasma concentrations of catecholamines and different responses to intravenously infused adrenaline compared to weight-stable individuals. Eight malnourished cancer and 10 non-cancer patients (11% weight loss) were compared to seven well-nourished and weight-stable patients. Adrenaline was infused i.v. at a rate of 0.005 microgram min-1 kg-1 body weight during 40 min followed by a 40 min rest period (without infusion) and then a final 40 min period with i.v. adrenaline infusion (0.02 microgram min-1 kg-1 body weight). Plasma glycerol concentration at fast was higher in weight-losing patients compared to weight stable individuals. Whole body oxygen uptake, carbon dioxide production, heart rate and plasma concentrations of free fatty acids (FFA) increased while the mean arterial pressure decreased significantly in response to adrenaline infusion at 0.02 microgram kg-1 min-1 in both weight-losing and weight-stable patients. Adrenaline at 0.005 microgram kg-1 min-1 increased plasma FFA levels by 19% (P less than 0.05) in weight-losing patients while no significant alteration was observed in well-nourished patients. Adrenaline infusion at 0.02 microgram kg-1 min-1 decreased the mean arterial blood pressure and stimulated respiratory gas exchange and heart rate significantly more in weight-losing than in weight-stable patients. The slopes for oxygen uptake, carbon dioxide production, heart rate, plasma FFA and plasma glycerol vs. plasma adrenaline and noradrenaline were all significantly steeper (P less than 0.05-0.01) in malnourished patients than in well-nourished controls. The present study suggests an increased sensitivity to adrenaline in weight-losing patients compared to matched controls with normal nutritional state and stable weight. PMID- 2582732 TI - Limitation of finger systolic pressure measurement as a diagnostic test for primary Raynaud's phenomenon in a female population. AB - The diagnostic value of measurement of the finger systolic pressure (FSP) was assessed during combined local and whole body cooling in a population-based sample of women with a medical history of primary Raynaud's phenomenon. Forty women had mild Raynaud's phenomenon and 40 had pronounced Raynaud's phenomenon. The results were compared with subjective assessments of complaints from Raynaud's phenomenon as indicated on a visual analogue scale (VAS) in the same group of women. The mean FSP at 10 degrees C was significantly lower in the patients than in 24 age- and sex-matched controls, but there was a large overlap in individual responses. The sensitivity of the FSP method was only 51% for the whole group with primary Raynaud's phenomenon. There was no significant difference in FSP at 10 degrees C between subjects with mild and those with pronounced Raynaud's phenomenon. The subjective severity of the symptoms as indicated on VAS was significantly higher in these two combined groups than in the controls. The mean VAS value was significantly higher in the group with pronounced Raynaud's phenomenon (P less than 0.01) than in that with the mild type. The low sensitivity of FSP measurement implies that this method is of limited value as a diagnostic test in subjects with primary Raynaud's phenomenon. Furthermore, there was no significant correlation between FSP and the VAS values (r = 0.23). PMID- 2582733 TI - Fluorescein angiography and distal arterial pressure in patients with arterial disease of the legs. AB - Fluorescein angiography (FA) of the foot soles was performed in 119 patients with arterial disease of the legs. Fluorescein was injected rapidly intravenously and sequential photographs were taken of the foot soles. Densitometric measurements were performed on three areas of each foot image: the big toe, the foot pad (just proximal to the little toe) and the heel. The relationships between different FA measurements and systolic arterial pressure in the ankle or the big toe were analysed. The appearance times of fluorescence correlated inversely with ankle pressure (P less than 0.001). The initial slopes of the fluorescence-time curves at all three sites of measurement correlated with ankle pressure (P less than 0.001). The initial slopes of fluorescence-time curves of the big toe and the foot pad correlated with toe pressure (P less than 0.001). In 12 patients effective arterial pressure was lowered by elevation of the feet, and in eight patients external pressure was applied to the foot by enclosing it in a box. The changes in FA evoked by these manoeuvres further strengthened the relationship between arterial pressures and FA measurements. We conclude that FA is a good method for evaluating circulation in the foot when neither ankle nor toe pressure is obtainable. In addition, FA may be useful when vascular disease is suspected in the presence of normal pressures, because the fluorescence distribution pattern was clearly abnormal in 11 of 16 such feet. PMID- 2582734 TI - Meal-induced thermogenesis in obese patients before and after weight reduction. AB - The purpose of this study was to find out whether human obesity is associated with a diminished meal-induced thermogenesis and, if so, to what extent this response is influenced by weight reduction. Ten obese subjects (body mass index 42 +/- 2) and 10 age- and sex-matched non-obese volunteers were studied with continuous indirect calorimetry in the basal state and after the ingestion of a standardized test meal. Six obese subjects (body mass index 44 +/- 2) were examined on two occasions, once before and once after gastric banding and an average weight reduction of 18 +/- 3 kg. Basal oxygen uptake and energy expenditure were 30% (P less than 0.001) greater in the obese subjects compared to non-obese controls. After the meal, pulmonary oxygen uptake and energy expenditure increased rapidly and reached a relatively constant level after 60 min; for pulmonary oxygen uptake the average rise above basal was less in the obese (17.7 +/- 1.6%) than the non-obese (27.8 +/- 1.9%, P less than 0.001); the increase in energy expenditure was 18.5 +/- 1.7% in obese and 30.8 +/- 2.1% in non-obese subjects (P less than 0.001). After weight reduction, oxygen uptake and energy expenditure in the basal state were 20% lower (P less than 0.05) than before weight reduction. The average post-prandial increase in oxygen uptake was greater after weight reduction (24.8 +/- 2.0%) than before (16.7 +/- 1.6%, P less than 0.001). Corresponding values for energy expenditure were 27.2 +/- 2.2 and 18.2 +/- 2.2% (P less than 0.001). It is concluded that: (1) the thermogenic response to a mixed meal is lower in obese compared to non-obese individuals; and, (2) this impaired response is partly normalized after weight reduction. These findings suggest that a diminished meal-induced thermogenesis is a secondary phenomenon rather than a primary pathogenic factor in human obesity. PMID- 2582735 TI - Does post-tetanic potentiation compensate for low frequency fatigue? AB - The purpose of this study was to examine the effect of post-tetanic potentiation on low frequency fatigue in adult human quadriceps muscle. Sixteen subjects (10 male and six female) performed three 60 s sets of knee extension exercise in order to induce low frequency fatigue (reduction in torque output at 10 and 20 Hz). The potentiating stimulus (a 10 s maximal voluntary contraction) induced a 58% increase in twitch tension (Pt) during the pre-fatigue state. Immediately following the fatiguing exercise, torque (X +/- SE, Nm) at 10 and 20 Hz (submaximal transcutaneous stimulation, 50 microsecond pulses) decreased (P less than 0.05) from 54.8 +/- 5.8 and 94.9 +/- 9.6 to 40.3 +/- 6.1 and 77.0 +/- 11, respectively. Although potentiation at this time increased Pt from 40.9 +/- 4.0 to 54.8 +/- 3.7 (P less than 0.05), torque at 10 and 20 Hz was unaffected. At 60, 120 and 240 min post-contraction, torque at 10 and 20 Hz remained depressed. Following potentiation, which increased twitch tensions to between 64 and 75%, torque at 10 Hz was increased (P less than 0.05) at 60 min (36.3 +/- 4.1 vs. 50.7 +/- 6.2), 120 min (40.8 +/- 6.3 vs. 56.5 +/- 8.9) and 240 min (42.0 +/- 4.7 vs. 57.5 +/- 8.3) of recovery. Similar effects were also noted at 20 Hz. These findings indicate that post-tetanic potentiation can overcome the low frequency fatigue during the post-contraction period and restore torque to pre-exercise levels. PMID- 2582737 TI - Working after heart attack. PMID- 2582736 TI - The management of heart failure. PMID- 2582738 TI - Gastrointestinal disorders associated with AIDS. PMID- 2582739 TI - Ribavirin inhibits proliferation of bovine respiratory syncytial virus in vitro. AB - Bovine respiratory syncytial virus (BRSV) is an important pathogen in bovine respiratory diseases in the United States. Proliferation of the disease can reach epidemic proportions with mortality reaching as high as 20%. In vitro work shown here suggests that the antiviral compound Ribavirin will be effective in the treatment of infected animals. Treatment at three dose levels with Ribavirin have shown significant inhibition of BRSV proliferation. Bovine turbinate cells were host cells for this study. Tissue culture specimens, infected and noninfected, were carried for 10 days. Presence of BRSV was verified with the use of monoclonal antibody. In addition, the infection with BRSV and consequential treatment with Ribavirin of calves demonstrated a noticeable reduction in viral symptom but no apparent systemic reaction to drug therapy. PMID- 2582741 TI - In vivo chemotaxis of oxidised lipids: 1. Chemotactic effects of oxidised arachidonic acid on rat leucocytes. AB - In vivo chemotaxis to rat leucocytes was shown to mildly oxidised arachidonic acid in the migration into cotton pellet method. Amounts of oxidised acid, 0.25, 0.5 and 2.5 mg, mobilized net leucocytes (mostly neutrophils) into experimental pellets in 12 h. The 0.5 mg of oxidised acid showed maximum chemotactic activity and attracted maximum net leucocytes into the experimental pellets at 12 h. Doses lower or higher than this were less effective. Equivalent doses of pure arachidonic acid failed to show these chemotactic activities but evoked inflammatory reactions at the experimental pellet sites. Chemotactic activity seemed therefore to require mild oxidation of the lipid. Oxidation also seemed to stimulate spontaneous migratory activity into the control pellets. PMID- 2582740 TI - Immunomodulatory properties of a strain of Mycobacterium chelonae. I. Mouse lymphocyte responses in vitro. AB - Immunomodulatory properties of a strain of live Mycobacterium chelonae (Mch) was investigated in an in vitro lymphocyte transformation system. Murine splenocyte activation by this bacterium was characterized by polyclonal lymphoproliferative responses in a dose dependent fashion. Optimal doses ranging from 20 to 80 micrograms of Mch (wet weight) per ml of cell suspension induced a very significant mitogenic effect. Higher doses (100 micrograms) of Mch manifested a decreased rate of tritiated thymidine ([3H] TdR) uptake whereas responsiveness of splenic lymphocytes to lower doses (0.156 microgram) was not modified. Contrary to the splenocyte responses activation of murine thymocytes by this mycobacterium is characterised by a decreased proliferation as compared to the background count of unstimulated cells. Simultaneous addition of Mch with optimal doses of Concanavalin A (Con A) and Phytohemaglutinin (PHA) potentiated polyclonal mitogenic responses of murine splenocytes to these two lectins. However, proliferation of these lymphocytes to Lypopolysaccharide (LPS) induction was not modified. BALB/C and DBA/2 spenocytes were found to be more responsive to stimulation by this Mycobacterium as compared to those of C3H/Ou and to a lesser degree to those of C57BL/6 mice. PMID- 2582742 TI - Isolation and plaque purification of a syncytial forming component of myxoma virus. AB - Using the endpoint dilution and plaque purification technique performed on rabbit kidney cells, two stable syncytial clones of myxoma virus have been isolated. No eosinophilic intracytoplasmic inclusion bodies nor intranuclear granulations could be detected in cells infected with these clones. Traditional plaques with the central area of detached cells surrounded by round cells also could not be recognized. However, when enough virus was added, one large complete syncytium developed in 24 on the monolayer. Syncytial activity was associated with the entire particle. This was the first time that myxoma virus is reported to demonstrate such an intense syncytial activity. PMID- 2582743 TI - Fuzzy model of inexact reasoning in medicine. AB - In this paper a fuzzy model of inexact reasoning in medicine is developed. Both diagnosis and choice of therapy are considered. In the context of diagnosis a model used as the mathematical basis of MYCIN is given in a fuzzy interpretation. Single combining functions are identified with basic fuzzy operations and principles. In choosing therapy, the approach adopted in MYCIN formalized in fuzzy set terminology. A modified model of therapy selection is developed based upon the certainty factors of possible significant organisms' identities. PMID- 2582744 TI - A new therapeutic parameter and computer control to approach optimal haemodialysis. AB - A two-compartmental (intracellular and extracellular volumes) patient model is being employed to derive the time variation of dialysis rate, which is required to meet the criterion that the intercompartmental concentration difference should not exceed the maximum value the patient could tolerate during dialysis treatment. Dialysate flow rate is the operational variable selected for controlling the dialysis rate. The maximum intercompartmental solute concentration difference allowable for individual patients is suggested as a new therapeutic parameter. The model algorithm and a personal computer can be linked with the delivery pump to monitor the dialysis treatment so as to avoid the disequilibrium syndrome and thus rationalise the entire procedure of dialysis. PMID- 2582745 TI - Statistical tests of the IBM PC pseudorandom number generator. AB - The widespread use of IBM personal computers in biomedical research and medical practice is evidenced by a variety of journal articles. Many of the application programs are written in the BASIC language, they model a stochastic process, and they depend on the Microsoft random number generator. Unfortunately, the Microsoft generator has exhibited a number of flaws including, for some seeds, a lack of uniformity of generated sequences of numbers, and serial correlation within such sequences. This paper provides evidence of these problems for several seeds, and provides suggestions for acceptable seeds which ensure that the generated sequences of numbers pass two fundamental statistical tests for randomness. PMID- 2582746 TI - Computerized collection and analysis of dietary intake information. AB - A computer system has been developed which facilitates standardized and in-depth collection and analysis of dietary intake information required for nutritional research. The system uses a hierarchically arranged database of food descriptions. A user identifies a consumed food by traversing a hierarchy and reaching a leaf node food item via a succession of selections from menu displays. If a food contains ingredients or was cooked with additional fat or salt, multiple traversals of the food hierarchies are necessary. The system assigns one or more food codes and determines the gram weight of the food consumed using everyday measures such as cups, slices, ounces, etc. It then uses these food codes and gram weights to calculate nutrient content. Utilizing binary trees and physical pointers to expedite data retrieval from this nearly 10 Mbyte database permits the system's use in conducting real-time interactive interviews. PMID- 2582747 TI - Single exposure dual-energy digital radiography. AB - This study presents preliminary results of single kVp dual-energy computed radiography using laser stimulable luminescent phosphor image plate detectors. The single kVp technique makes use of four of these plates in a single cassette, each plate acting as an X-ray filter to the next so that the energy separation required for the dual-energy basis decomposition is achieved. An analysis to determine the best operating technique for the chest is performed using computer stimulation, and was found to be 85 kVp and 14 mAs. This technique yields the same entrance exposure value as is used clinically, so that the information for the decomposition is obtained without additional dose to the patient. The iso transmission line technique was used as the decomposition algorithm. A humanoid chest phantom was used to demonstrate the quality of the resulting calibration material equivalent images. PMID- 2582748 TI - A flexible nurse scheduling support system. AB - Salaries paid to nursing personnel constitute the largest chunk of a hospital's budget. Therefore, this human resource must be utilized efficiently. Hospitals provide continuous service without the exception of holidays and personal preferences. This causes the nurses' discontent in shift scheduling. And the consequence of this discontent is the nurse shortage. This and the pressures on hospitals to limit costs increase the importance of the nurse scheduling problem. Scheduling nursing personnel in hospitals is very complex due to the variety of conflicting interests or objectives between hospitals and nurses. Also, the demand, which varies widely 24-h a day 7-day a week is skill specific and hard to forecast. In the face of this complexity, the present nurse scheduling models have met with little success. In this paper, we propose a more flexible decision support system that will satisfy the interests of both hospitals and nurses through alternative models that attempt to accommodate flexible work patterns as it integrates time of the day (TOD) and day of the week (DOW) scheduling problems. PMID- 2582749 TI - An object-based architecture for biomedical expert database systems. AB - Objects play a major role in both database and artificial intelligence research. In this paper, we present a novel architecture for expert database systems that introduces an object-based interface between relational databases and expert systems. We exploit a semantic model of the database structure to map relations automatically into object templates, where each template can be a complex combination of join and projection operations. Moreover, we arrange the templates into object networks that represent different views of the same database. Separate processes instantiate those templates using data from the base relations, cache the resulting instances in main memory, navigate through a given network's objects, and update the database according to changes made at the object layer. In the context of an immunologic-research application, we demonstrate the capabilities of a prototype implementation of the architecture. The resulting model provides enhanced tools for database structuring and manipulation. In addition, this architecture supports efficient bidirectional communication between database and expert systems through the shared object layer. PMID- 2582751 TI - A picture archiving and communication system module for radiology. AB - This paper presents the design and implementation of a clinical picture archiving and communication system (PACS) module within the radiology department of a 700 bed teaching hospital. The system is composed of an integrated network of digital devices used to electronically acquire, store, manage, and display radiological text and image information. Operationally the system behaves as a large queueing network allowing processes to operate concurrently in a coordinated and prioritized fashion. Secondary reviews (radiology conferences and fast case reviews by clinicians) are being conducted from a 512 X 512 CRT viewing station. Preliminary evaluation based on formal survey and usage statistics shows that the system is rapidly being accepted by radiologists and clinicians for the review and processing of digital radiographic images. PMID- 2582750 TI - Improving drug dosing in hospitalized patients: automated modeling of pharmacokinetics for individualization of drug dosage regimens. AB - Many clinical useful drugs have a narrow range of blood concentrations which are both safe and efficacious. Inter-individual and intra-individual variations in drug disposition are important factors causing blood concentrations of drug to fall outside of the therapeutic range. Modeling of the pharmacokinetics of the individual offers an effective approach to the problem of variation in drug disposition. Previous approaches for the modeling of individual pharmacokinetics have required either extensive computations or access to computer software and hardware in the clinical environment, and special expertise to interpret the results. This paper describes a prototype computer program, PK Monitor, which can, when connected with an appropriate interface, automatically monitor drug dosing and recommend changes that may be required to obtain blood concentrations in the therapeutic range. The software can also detect the occurrence of change in drug disposition which will lead to concentrations outside of the therapeutic range, identify potentially erroneous blood concentration measurements, and assess the need for further blood concentration measurements. This program will be an integral part of the MENTOR therapeutic monitoring system of programs. PK Monitor awaits a complete evaluation with the rest of the MENTOR system, but preliminary simulations suggest reasonable sensitivity and specificity in monitoring for unexpected data and change. PMID- 2582752 TI - A desktop computer-based workstation for display and analysis of 3- and 4 dimensional biomedical images. AB - While great advances have been made in developing new and better ways to produce medical images, the technology to efficiently display and analyze them has lagged. This paper describes design considerations and development of a workstation based on an IBM PC/AT personal computer for the analysis of three- and four-dimensional medical image data. PMID- 2582753 TI - Variations on the family resemblance hypothesis as applied to personality disorders. AB - Diagnosis and classification of the personality disorders is controversial and problematic. Diagnostic reliability is uneven because of overlapping of traits and the lack of clear boundaries between categories. This study demonstrates that personality disorder diagnosis is dependent on the total number of defining features. Clinicians tend to ignore the presence of conflicting features when making a diagnosis. A new research instrument, artificially created case histories that allow the specific manipulation of defining features (i.e., diagnostic criteria), is described. PMID- 2582754 TI - Comparison of 6- with 9-week trials of adjunctive imipramine in postpsychotic depression. AB - Outcome at 6 weeks versus outcome at 9 weeks was compared in 23 patients with syndromally defined episodes of postpsychotic depression who underwent a trial of adjunctive imipramine added to their continuing treatment with fluphenazine decanoate and benztropine. The global outcome after 9 weeks was found to be superior. The implications of this finding for the treatment of secondary depressions in patients with schizophrenia and schizoaffective disorder is discussed. PMID- 2582755 TI - Compounded depression and family functioning during the acute episode and at 6 month follow-up. AB - Thirty-seven inpatients with pure major depression were compared with 41 inpatients with compounded depression (major depression with coexistent axis I, II, and/or III disorders) to assess the impact of the patients' illness on their families. Families of patients with compounded depression had worse family functioning (especially in their ability to solve problems and in maintaining acceptable standards of behavior), both during the acute depressive episode and at 6-month follow-up. A significantly smaller percentage of patients with compounded depression had recovered by 6 months (28%) than those with pure depression (51%). PMID- 2582756 TI - Accidents among schizophrenic outpatients. AB - A preliminary comparison of traffic, home, and work accident incidence was performed among 103 outpatient schizophrenic patients and an age matched sample of 123 controls. The number of motor vehicle drivers among schizophrenic outpatients was far less than among controls (70 of 103 versus 122 of 123; P = .00001). Among those who did drive, schizophrenic patients drove far less than controls (19 of 70 patients driving greater than or equal to 5,000 miles per year versus 81 of 122 controls; P = .0001). Patients also reported more accidents per miles driven than did controls, consistent with previous studies. Older patients reported more home accidents than did younger patients (five of eight for those over 55 years versus four of 95 for those less than 55; P = .0007); no similar effect was observed among controls. Schizophrenic outpatients may be at greater risk of motor vehicle accidents per miles driven than age matched controls; elderly patients may be at higher risk of home accidents as well. PMID- 2582758 TI - Loss in childhood: anxiety in adulthood. AB - Recent research, especially in Great Britain, has attracted interest by reporting on the relationship between maternal loss and vulnerability to depression among women. Several studies in the United States that included men have not received equal attention. The present study expands on the US work by reporting findings from the Queensbrook Study in New York City, a cross-sectional survey that provides information about the relationships between the family environment of childhood and the prevalence of psychiatric illness in adulthood. The Queensbrook survey was conducted in the mid 1960 as an urban counterpart to the Stirling County Study in rural Atlantic Canada. The data from the urban sample described here were not published earlier, and for this report we used DSM-111 criteria to develop scoring algorithme to identify depression and anxiety. We investigated several types of adverse childhood losses, not solely the death of a mother, and related them to depression and anxiety in both men and women. None of the childhood experience was significant associated with these disorders among women, nor was the death of a parent related to either type of disorder among men. However, boys who left home before 16 years of age, whose parents were divorced or separated, or who were placed in an adopted family had a threefold increase in rates of anxiety as adults. This finding of a positive association between the divorce of parents and later anxiety in men is supported by several of the other population surveys carried out in the United States. PMID- 2582759 TI - The neurological legacy of psychoanalysis: Freud as a neurologist. PMID- 2582757 TI - Psychiatric admissions due to adverse drug reactions. AB - This is a report of the findings of a 6-year study of hospitalizations caused by adverse psychiatric reactions to prescribed medications. Of 15,800 consecutive psychiatric admissions to two university hospitals, 112 (0.7%) were caused by adverse reactions to medications. In 67% of cases these admissions were due to extrapyramidal symptoms such as parkinsonism and/or akathisia, and coexisting neuroleptic-related depression. In 25% the admitting diagnosis was drug-induced delirium or psychosis; one third of these patients suffered from Parkinson's disease and had been treated with a combination of two or more antiparkinsonian agents. Older age, polydrug therapy, and the parenteral administration of neuroleptics at high dosages were important risk factors for severe adverse drug reactions leading to hospitalization. PMID- 2582761 TI - Intraoperative disseminated intravascular coagulation in a patient with ulcerative colitis. AB - A patient with acute ulcerative colitis who developed acute disseminated intravascular coagulation during the course of a proctocolectomy is presented. Ulcerative colitis may represent a rare cause of acute disseminated intravascular coagulation. PMID- 2582760 TI - Continent reservoirs. AB - Continent urinary diversion is a major advance in the treatment of selected patients following cystectomy. Twenty-eight patients have undergone some form of continent urinary diversion at Yale New Haven Hospital during the past three years; thirteen have a continent reservoir with a continent stoma on the abdominal wall, and empty the urine by self-intermittent catheterization, and 15 have a reservoir anastomosed to the urethra, the majority of whom void spontaneously. All are continent by day and over 50% are continent at night. A recent modification in the construction of the urinary reservoir would appear to have resolved the problem of nocturnal incontinence. The results and urodynamic studies in this group of patients are discussed, and it is concluded that a detubularized intestinal reservoir provides a safe and effective method for continent urinary diversion in selected patients following cystectomy. PMID- 2582762 TI - More on the world's longest insulin patient. PMID- 2582763 TI - Oral complications of cancer therapies: diagnosis, prevention, and treatment. National Institutes of Health. PMID- 2582764 TI - Animals and human life. PMID- 2582765 TI - JCAHO. PMID- 2582766 TI - Life after Webster: the more things change.... PMID- 2582768 TI - Uterine cavity and the location of IUDs following administration of meclofenamic acid to menorrhagic women. A pilot study. AB - The relationship between the uterus and the IUD was studied selectively with hysterosalpingograms in 18 menorrhagic women previously treated with Meclofenamic acid (M Ac.), a well known anti-inflammatory drug. Major anomalies (embedding, perforation, rotation) were found in 28.6% of those patients who responded positively to M Ac. In contrast, major anomalies were found in 63.6% of those patients who responded negatively to the drug. It is proposed that the negative response to M Ac. might be due to severe macroscopic disturbances of the uterine wall-IUD relationship. The degree of response to M Ac. might contribute to the decision to remove the IUD from menorrhagic women. In addition, 84.7% anomalies (deformities, embedding, perforation) in the uterine-IUD relationship were found in 13 women with a T-shape IUD device. The fact that those anomalies are related to the tip of the horizontal arm justifies future studies using shortened arms to diminish hypermenorrhea induced by T-shape devices or attempts to use IUDs which do not have the conventional plastic frame, as in the Cu-Fix IUD which has been mentioned as particularly useful to prevent bleeding side effects and pain induced by conventional IUDs. The Cu-Fix IUD consists of 6 sleeves made of pure (99.99%) copper, each sleeve with a length of 5 mm and an outer diameter of approximately 2.2 mm, threaded on surgical 00 monofilament polypropylene (ProleneR, Ethicon). The total area of exposed copper is approximately 390 mm2. The sleeves are prevented from sliding off the suture by 2 smaller copper tubules crushed on the thread in both ends of the IUD structure. This thread-type, copper bearing device has been designed to overcome the most common IUD-related problems, bleeding and pain. PMID- 2582767 TI - Changes in menstrual blood loss after four methods of female tubal sterilization. AB - One-hundred females requesting tubal sterilization were included in this study. They were enrolled into 4 groups, each n = 25. They were allocated to a particular method of sterilization on a randomized basis. The four modalities used were: laparoscopic Falope ring application, bipolar electrocoagulation, Hulka clip application and Pomeroy tubal ligation via minilaparotomy. The menstrual blood loss (MBL) was quantitatively estimated, using the alkaline hematin method, prior to sterilization and after 3, 6 and 12 months. No significant changes in MBL were observed after the four sterilization techniques. Moreover, they did not differ significantly in this context. PMID- 2582770 TI - Pharmacokinetic study of orally administered RU 486 in non-pregnant women. AB - A method based on HPLC was devised for the estimation of RU 486 in blood and utilised to study the pharmacokinetics of a single dose of 50 mg RU 486 administered orally to 12 women on day 7 of the cycle. The dose was rapidly absorbed with peak plasma concentration between 1 and 2 hours. Distribution was also rapid (mean t1/2 alpha: 1.4h), whereas elimination was slow (mean t1/2 beta: 28.3 h). RU 486 was still detectable in some women at 72 h after administration. The plasma concentrations fitted the equation for a two-compartment open model from which the pharmacokinetic parameters were calculated. The mean total plasma clearance was 3.0 l/h, and the comparison of our data with those published studies suggests that the pharmacokinetics of RU 486 in Chinese women are similar to those of other populations. PMID- 2582771 TI - Single dose pharmacokinetics of gestodene in women after intravenous and oral administration. AB - Six healthy female volunteers (age 25 - 39 years) received 75 micrograms gestodene intravenously followed by 3 oral administrations of 25, 75 and 125 micrograms gestodene together with 30 micrograms ethinylestradiol (EE2) in a cross-over design. Gestodene plasma levels were determined using a specific RIA. After intravenous administration, plasma gestodene concentrations decayed triphasically with mean half-lives of 0.16 h, 1.5 h and 10 hours. The area under the plasma level curve, the total plasma clearance and the volume of distribution (VZ) were as follows: AUC = 35 +/- 15 ng.h/ml, CL = 0.80 +/- 0.53 ml/min/kg, and VZ = 0.66 +/- 0.43 1/kg, respectively. After oral administration of all doses, maximum plasma levels of 1.0 (25 micrograms), 3.8 (75 micrograms) and 7.0 ng/ml (125 micrograms) were achieved between 1.4 and 1.9 hours after the intake. Post maximum levels showed 2 disposition phases with half-lives of 1 and 12 - 14 hours. Absolute bioavailabilities were calculated as 87.5 +/- 17.5% (25 micrograms), 99.3 +/- 10.9% (75 micrograms) and 110.8 +/- 17.7% (125 micrograms) indicating that gestodene is completely absorbed and systemically available at all doses investigated. PMID- 2582769 TI - Blood loss following induction of early abortion using mifepristone (RU 486) and a prostaglandin analogue (gemeprost). AB - The pattern and amount of blood loss following induction of therapeutic abortion using mifepristone (RU 486) and a prostaglandin E analogue (gemeprost) was studied in 222 women of less than 63 days amenorrhoea. A single oral dose of mifepristone (400, 500 or 600 mg) was followed 48 hours later by a half or 1 mg gemeprost vaginal pessary. Complete abortion occurred in 218 (98%) women without necessity for surgical evacuation of the uterus. Bleeding commonly occurred following administration of mifepristone and prior to prostaglandin administration. The median duration of bleeding following abortion was 13 days with a range of from 1 to 44 days. There was a wide individual variation in measured blood loss between women, from 14 to 512 ml, with a median loss of 74 ml. The amount of blood loss was independent of the dose of mifepristone or prostaglandin but was significantly correlated with gestation. These results confirm that the combination of mifepristone and gemeprost is a highly effective and safe method of inducing therapeutic abortion medically. As the amount of blood loss increases with increasing gestation, it is suggested that its use should be restricted to women with amenorrhoea less than or equal to 56 days. PMID- 2582772 TI - The contraceptive sponge: factors in initiation and discontinuation of use. AB - This study examined characteristic of the contraceptive sponge that were important in women's decisions to use the contraceptive sponge and reasons why women discontinued sponge use. A sample of 385 current sponge users and 407 former sponge users participated in a national telephone survey on sponge use. Important reasons for trying the sponge were effectiveness, comfort, convenience and ease of use and it "would not interfere with sexual pleasure." The media and physicians were of considerable influence in women's decisions to initiate sponge use, but sexual partners, friends, parents and relatives exerted little influence. The most important reasons for discontinuing use of the sponge were pregnancy, both planned and accidental, and irritation, discomfort or vaginal infection. Women may decide to use the sponge because they have unrealistically positive perceptions of sponge characteristics. PMID- 2582774 TI - Conjugate vaccines. PMID- 2582773 TI - The vaginal contraceptive diaphragm and the condom--a reevaluation and comparison of two barrier methods with the rhythm method. AB - The use-effectiveness and continuation rates of two barrier methods of contraception, the diaphragm and condom, were studied during a two-year follow-up in a group of 85 and 98 women, respectively. All were highly motivated. Results were compared to a group of 64 women using the periodic abstinence or rhythm method, i.e. not using any contraceptive. The patients selected the method of contraception they preferred and were instructed in their proper use. Results showed good continuation rates in the groups using a diaphragm and the condom for 2 years, for a total follow-up of 5570 cycles. Pregnancy rate after 24 months of use, as calculated by Pearl's formula, was 2.48 for the diaphragm, 3.21 for the condom, and 5.19 in the rhythm group. No serious side effects or complications occurred in either group. The study demonstrated a fair acceptability and use effectiveness for barrier contraceptive. We suggest that these harmless and complication-free methods may still be reasonable alternatives for the "modern" methods, the pill and the IUD. PMID- 2582775 TI - B lymphocytes: function and regulation. PMID- 2582776 TI - Single-dose kinetics of recombinant human erythropoietin after intravenous, subcutaneous and intraperitoneal administration. Preliminary results. PMID- 2582777 TI - Correction of the anaemia of chronic renal failure with erythropoietin: pharmacokinetic studies in patients on haemodialysis and CAPD. PMID- 2582778 TI - Pharmacokinetics of recombinant human erythropoietin after SC administration and in long-term IV treatment in patients on maintenance hemodialysis. PMID- 2582779 TI - Site of erythropoietin formation. PMID- 2582780 TI - Subcutaneous recombinant erythropoietin in the treatment of renal anaemia in CAPD patients. PMID- 2582781 TI - Correlation of the molecular and anatomical aspects of renal erythropoietin production. PMID- 2582782 TI - Influence of erythropoietin treatment on endocrine abnormalities in haemodialyzed patients. PMID- 2582784 TI - Blood rheology in hemodialysis patients treated with recombinant human erythropoietin. PMID- 2582783 TI - Peripheral hemodynamics, blood viscosity, and the renin-angiotensin system in hemodialysis patients under therapy with recombinant human erythropoietin. AB - Treatment of renal anemia with rhEPO (120 U/kg body weight/hemodialysis) in transfusion-dependent patients on maintenance hemodialysis led to an increase in blood pressure, regional peripheral resistance and whole blood viscosity. Our results are in agreement with earlier findings that partial correction of renal anemia results in hemodynamic changes characterized by a fall in cardiac output together with an increase in blood pressure due to increased vascular resistance. The increase in whole blood viscosity correlated with the increase in regional peripheral resistance but not with the increase in mean arterial blood pressure. Thus, other regulating factors of vascular resistance must be involved. Correction of renal anemia does not influence the reninangiotensin system. However, peripheral responsiveness of vascular smooth muscles may have changed due to improved tissue oxygenation and thus leading to an increase in vasoconstriction. PMID- 2582786 TI - Erythropoietin metabolism in the isolated perfused rat liver. PMID- 2582785 TI - The in vivo metabolism of recombinant human erythropoietin. PMID- 2582787 TI - Continuous arteriovenous ultrafiltration: a monitoring guide for ICU nurses. AB - CAVU has been demonstrated to be a therapeutic intervention for certain critically compromised patients. The objectives of this therapy can be achieved if nurses and physicians are aware of the procedural considerations before, during, and after therapy that enhance effective management. Continuing in service education, established departmental protocols, and comprehensive guidelines for monitoring are not only extremely helpful but necessary to assure quality patient care. PMID- 2582788 TI - Continuous arteriovenous hemodialysis in the ICU. PMID- 2582789 TI - The patient with lower urinary tract trauma. AB - The nursing care of the patient with lower urinary tract trauma depends upon the location and extent of the injury. Following stabilization of the airway, breathing, and circulation (and after neurologic evaluation) the nurse focuses on abdominal and urinary tract assessment. By using the results of a physical examination, diagnostic testing, and urinalysis, the nurse develops a plan of care. This plan provides the patient with relief of pain, control of infection, emotional support, and management of alterations in fluid and electrolyte balance. Early recognition of the extent of injury and knowledgeable management of potential complications from injury enable the critical care nurse to maximize the patient's own compensatory mechanisms and minimize long-term effects. PMID- 2582790 TI - Special touches in perinatal care. PMID- 2582791 TI - Arterial blood gas evaluation: metabolic acidemia. PMID- 2582792 TI - Compassion: a strategy for avoiding a lawsuit. PMID- 2582793 TI - VT or SVT? PMID- 2582794 TI - Recognizing critical care nurses. PMID- 2582795 TI - Calcium channel blockers: nursing care for hypertension. AB - Calcium channel blockers are gaining wider use in patients with cardiac disease, particularly hypertension and angina. The nurse must be aware of the actions, side effects, and interactions of these agents if they are to be administered safely. PMID- 2582796 TI - Rapid initiation of thrombolytic therapy for acute MI. PMID- 2582797 TI - Improving time management. PMID- 2582799 TI - Compatibilities and stabilities of i.v. preparations. PMID- 2582798 TI - Evaluating an ICP epidural catheter. PMID- 2582800 TI - Imipenem-cilastatin sodium. PMID- 2582801 TI - Readership survey: critical care orientation programs. PMID- 2582802 TI - Ventricular burst pacing--an alternative to electric countershock for terminating ventricular arrhythmias. PMID- 2582803 TI - Promoting sleep for the patient with a myocardial infarction. PMID- 2582804 TI - Applying the Roy adaptation model to the CCU. PMID- 2582805 TI - Percutaneous transluminal valvuloplasty. PMID- 2582807 TI - ECG lead placement and configuration. PMID- 2582808 TI - Evaluating the impact of educational programs in critical care settings. PMID- 2582809 TI - Participate in the future of critical care nursing. PMID- 2582806 TI - Developing competency-based orientation for six critical care units. PMID- 2582810 TI - Chronic pain is a big problem in health care today. PMID- 2582812 TI - Training and development of the ICU nurse for critical care transport. PMID- 2582811 TI - Quality care: the emerging role of the CNS. PMID- 2582813 TI - Understanding disruptive behaviors in the critical care setting. PMID- 2582814 TI - Caring: the essence of nursing. PMID- 2582815 TI - Phenylephrine. PMID- 2582816 TI - Double tachycardia. PMID- 2582817 TI - Care of the family of the ICU patient. AB - A nurse working in intensive care may easily forget the first impact this environment makes and therefore may unintentionally overlook a family's needs. It is hoped that this article will help nurses recognize the importance of easing stress within the family as well as provide the tools to meet the needs of each family whose loved one enters an intensive care unit. PMID- 2582818 TI - Opting-in versus opting-out: an organ procurement dilemma. PMID- 2582819 TI - Teaching after CABG surgery: a family affair. AB - CABG surgery is a stressor that severely compromises the integrity of the family. In the role of teacher, the critical care nurse can function as a catalyst to facilitate the togetherness of the family. This goal may be achieved by the nurse using easily planned and presented teaching-learning strategies described in this article. Family wholeness can be encouraged by the nurse instructing both the patient and spouse in the basic skills and general knowledge necessary to perform postoperative care. In this capacity, the nurse can also establish a foundation for life-long commitment to healthful behaviors. Thus, the instruction of the nurse facilitates the mutual support needed by family members to achieve positive rehabilitation. Truly, teaching after CABG surgery is a family affair. PMID- 2582820 TI - A dyspnea assessment guide. PMID- 2582821 TI - Beta agonist delivery and the outpatient. PMID- 2582822 TI - Muscarinic autoreceptors in airways. Their possible role in airway disease. PMID- 2582823 TI - Allergistis non carborundum. PMID- 2582824 TI - Disparities in assessment of disease activity. PMID- 2582825 TI - Correlation of chest roentgenograms with pulmonary function and bronchoalveolar lavage in interstitial lung disease. AB - We used the ILO classification for occupational lung disease to determine whether there was any correlation between the type and/or severity of pulmonary infiltration on chest roentgenograms and either pulmonary function tests or the types of inflammatory cells present in BAL fluid in patients with interstitial lung disease. Of the 62 patients evaluated (27 with sarcoidosis, 18 with IPF, and 17 with a CV disease and lung involvement), 49 had irregular linear opacities and 13 had normal chest x-rays. There were no significant correlations between the types of cells present in BAL fluid and the various categories of infiltrate or profusion of the infiltrates within each disease group. In patients with sarcoidosis, more extensive infiltration (profusion) was associated with lower FEV, (p less than 0.01). In patients with IPE, linear opacity type, profusion, and the presence or absence of honeycombing were not related to the severity of pulmonary function abnormalities. We conclude that the ILO classification for analysis of chest roentgenograms can be applied to patients with interstitial lung disease not associated with an occupational exposure and that this approach is useful, especially for communication. However, these data provide no information regarding the inflammatory process in the lung and limited information regarding abnormalities in pulmonary function. PMID- 2582826 TI - Transbronchial needle aspiration for histology specimens. AB - Fine-gauge (22-G) transbronchial needle aspiration (TBNA) has significantly added to the diagnostic yield of FOB, and in some institutions has become routine in staging bronchogenic carcinoma. Cytologic examination of the specimen obtained by n228G TBNA, however, has several limitations. The mediastinal aspirate can be contaminated by tumor cells from respiratory secretions, giving false positive diagnoses of unresectability. The diagnosis of benign conditions can seldom be made. Using 18-G TBNA, we can obtain specimens for histologic examination from paratracheal, peribronchial, and carinal areas by FOB. Both 18-G and 22-G TBNA were performed in 34 patients with radiographic abnormalities involving mediastinal or hilar areas. Tissue for histologic examination was obtained in 17 patients (50 percent) using 18-G TBNA and was diagnostic in 11 (32 percent), including three patients with benign conditions. The overall diagnostic yeild of 18-G TBNA was 41 percent (14/34 patients), increasing the yield of FOB from 50 percent to 58 percent. There were no false positive results and few minor complications. 18-G TBNA is effective in obtaining tissue for histologic examination and diagnosing benign conditions. In selected cases this technique increases the diagnostic yield of FOB. PMID- 2582827 TI - Comparison of outpatient nebulized vs metered dose inhaler terbutaline in chronic airflow obstruction. AB - Eighteen patients (nine asthmatic patients and nine with poorly reversible airflow obstruction) with stable, severe chronic airflow obstruction, completed a four-week randomized, doubled-blind, placebo-control, crossover trial comparing the acute and chronic effects of terbutaline administered by metered-dose inhaler (MDI) and nebulizer (NEB). Equipotent doses of terbutaline were selected from the comparison of separate cumulative dose-response curves for MDI and NEB. The MDI and NEB given acutely produced similar bronchodilatation and improvement in exercise performance. Spirometric indices, 6 min walking distance, symptom scores and extra beta-agonist use were no different between MDI and NEB treatment fortnights in the outpatient study. We conclude that the degree of bronchodilatation achieved in these patients is a reflection of the dose of bronchodilator administered and not the mode of administration. There is no justification for the preferred outpatient use of nebulized bronchodilators in patients with stable chronic airflow obstruction who can use adequate doses of bronchodilators via a metered-dose inhaler. PMID- 2582828 TI - Nebulizer vs spacer for bronchodilator delivery in patients hospitalized for acute exacerbations of COPD. AB - This double-blind crossover study compared the efficacy of two methods of delivery (MDI-spacer and nebulizer) of inhaled albuterol to patients hospitalized for an acute exacerbation of COPD. Within 24 h of admission, 20 subjects (mean age, 69 years) with severe airflow obstruction (mean FEV, 0.69 L) were subjected to a treatment with an MDI-spacer (0.36 mg of albuterol or placebo) followed by treatment with a nebulizer (2.5 mg of albuterol or placebo). Active drug was given by only one device (randomly assigned in a double-blind manner), and the entire sequence was repeated in 4 h, with active drug given in the alternate device. Spirometric data and the Borg dyspnea score were obtained before and 1 h after each sequence of treatments. Treatment resulted in significant improvements in the FEV1, FVC, and Borg score. The percent improvement in the FEV1 was slightly larger after treatment with the nebulizer (16.7 percent vs 13.4 percent). Improvements in the Borg score were slightly larger after treatment with the MDI-spacer (-1.08 vs -0.73). However, these differences were not statistically significant. This study suggests that the MDI-spacer system is an effective method of sympathomimetic delivery in this setting, provided patients are able to master the technique. PMID- 2582829 TI - The relationship between pulmonary function and dyspnea in obstructive lung disease. AB - Increased importance is now being placed on evaluating dyspnea in patients with obstructive lung disease (OLD). We measured breathlessness at rest, using a Borg scale dyspnea index (BSDI) before and after bronchodilator albuterol [salbutamol] 200 micrograms) in 93 patients with OLD drawn from a larger population undergoing routine spirometry. The median BSDI declined from 3 to 1 before and after bronchodilator, suggesting improvement in dyspnea. However, there was no correlation between initial or postbronchodilator spirometry and BSDI. The change in FEV1 similarly did not correlate with the change in BSDI (r = 0.05). A large bronchodilator response was usually associated with improvement in dyspnea, but the converse was not observed. Thus, of ten patients with an improvement in BSDI of more than two categories, six had a change in FEV1 of 0.1 L or less after bronchodilator. Analyzing a subgroup of 65 dyspneic patients with an initial BSDI of 2 or more revealed the following response groups: those with either a bronchodilator or dyspnea response alone, both together, or neither. Twenty-eight patients (43 percent) responded both subjectively and objectively. Eleven (17 percent) had a bronchodilator response only, 17 (26 percent) had a dyspnea response only, while nine (14 percent) had neither measurable response. We conclude that dyspnea is poorly correlated with results of routine spirometry in patients with OLD. The use of dyspnea ratings may yield information about bronchodilator responsiveness not appreciated by spirometry alone. PMID- 2582830 TI - Noninvasive estimation of systolic pulmonary artery pressure using Doppler echocardiography in patients with chronic obstructive pulmonary disease. AB - In patients with acquired or congenital heart diseases, the systolic pulmonary artery pressure (PAPs) can be predicted using continuous-wave Doppler ultrasound (CWD) measurement of the peak velocity of a tricuspid regurgitation (TR) jet. The aim of this study was to determine whether CWD could be used to accurately estimate PAP in patients with chronic obstructive pulmonary disease (COPD). In 41 patients with stable COPD, we prospectively performed CWD and right heart catheterization. The mean value of PAPs for the entire group was 38.5 +/- 14.9 mm Hg. Pulmonary arterial hypertension (PAPs greater than or equal to 35 mm Hg) occurred in 51 percent (21/41) of patients. Doppler estimation of PAP was impossible in 34 percent (14/41) because of poor signal quality (n = 3), absence of Doppler-detected TR (n = 8), and inadequate TR Doppler signal (n = 3). The PAP could be estimated in 66 percent (27/41) of patients. A statistically significant correlation was found between the Doppler-estimated PAP and the catheter-measured PAPs (r = 0.65; p less than 0.001; SEE = 9 mm Hg). Therefore, CWD appears to be useful for the noninvasive estimation of PAP in patients with COPD. However, this method is associated with two limitations: (1) the high percentage of patients in whom the PAP cannot be estimated by CWD, mainly because of the absence of Doppler detected TR, and (2) the high value of the standard error of the estimate. The combination of CWD with other Doppler methods should increase the feasibility and accuracy of Doppler echography for the prediction of PAP in patients with COPD. PMID- 2582831 TI - Independent pulsed Doppler mapping techniques. Limitations in the prediction of the angiographic severity of mitral regurgitation. AB - Pulsed Doppler mapping of the flow disturbance of mitral insufficiency is commonly employed to estimate the severity of regurgitation. We re-examined the customary pulsed Doppler criterion of relative depth of jet penetration (MR ratio) in 50 patients undergoing left ventriculography and found a modest correlation (r = 0.70) between Doppler and angiographic estimates of regurgitant grade. The MR ratio did not provide statistically significant separation between adjacent angiographic grades 1+ to 3+ (scale 0 to 4+). However, when the data were re-analyzed for the subset of 36 patients with pure mitral regurgitation the correlation between Doppler and angiographic estimates of regurgitant grade improved dramatically (r = 0.88) and MR ratio provided statistically significant separation between all angiographic grades with the sole exception of the distinction between 1+ and 2+ regurgitation. The presence of restriction of the regurgitant orifice in the remaining 14 patients with relative mitral inflow obstruction may result in a nozzle effect on the regurgitant jet which alters the relationship between depth of jet penetration and severity of regurgitation. In this latter group of patients independent pulsed Doppler mapping techniques may provide inaccurate estimates of the angiographic severity of mitral regurgitation. PMID- 2582832 TI - Transbronchial needle aspiration in clinical practice. A five-year experience. AB - We conducted a five-year review of our use of TBNA during bronchoscopy in our clinical practice. Out of 1,630 bronchoscopic procedures, 633 patients (39 percent) had TBNA performed as part of the initial examination. Mediastinal nodes were sampled in 86 percent of the patients who had TBNA performed, and 127 (23 percent) of 547 of these aspirates were positive. Other areas of mucosal abnormality of the tracheobronchial tree were also sampled by TBNA under direct vision and showed malignant cells in 44 (25 percent) of 176 aspirates. Of 363 patients first diagnosed as having carcinoma of the lung who had TBNA of N2 nodes, 41 (59 percent) of 70 with small-cell tumors were positive, as were 83 (28 percent) of 293 with non-small-cell malignant neoplasms. Comparison of cytologic results obtained by TBNA with histologic material in 109 cases showed an excellent correlation. In 31 cases (4 percent of all TBNA), the aspirate provided the sole means of establishing the diagnosis of cancer. Two patients were thought to have false-positive aspirates. No complications of therapeutic significance were encountered. We believe that TBNA is a safe and effective way to assess mediastinal lymphatic involvement in the staging of lung cancer and that TBNA can be safely performed as part of the initial bronchoscopic examination in patients suspected of having malignant neoplasms of the chest. PMID- 2582833 TI - Predictive risk factors for periannular extension of native valve endocarditis. Clinical and echocardiographic analyses. AB - The study objective is to identify clinical, microbiologic, and/or echocardiographic risk factors present early in the course of native valve endocarditis that predict subsequent development of periannular extension of infection. A multivariate computer-generated analysis of 21 clinical microbiologic parameters and 11 two-dimensional echocardiographic parameters in patients with native valve endocarditis was designed. These parameters were statistically compared in operated-on patients with native valve endocarditis with and without periannular extension of infection. The study took place in a 600-bed acute-care, nonreferral, municipal hospital primarily servicing an indigent patient population. Seventy-three documented episodes of native valve endocarditis occurred between the years of 1973 and 1987, including 29 operated on patients with surgically confirmed periannular extension of infection and 44 operated-on patients without periannular extension of infection. Multivariate logistic-regression analyses of multiple clinical, microbiologic, and echocardiographic parameters which are potentially predictive of eventual periannular extension of native valve endocarditis were carried out. The only two independent parameters that significantly predicted periannular infection among patients with native valve endocarditis were (1) aortic valve involvement and (2) abuse of intravenous (IV) drugs (p less than 0.01; p less than 0.01, respectively, multivariate analysis). The relative risk of developing periannular extension of endocarditis among patients with aortic valve involvement and/or IV drug abuse was increased by approximately 2.5-fold compared with patients without these characteristics. Factors not significantly associated with increased risk of periannular extension of native valve endocarditis included the following: prolonged febrile morbidity; Staphylococcus aureus etiology; or two-dimensional echocardiographic demonstration of vegetations, large vegetations (greater than or equal to 1 cm), multiple vegetations, or enlargement of aortic root or annulus. These data suggest that patients with native aortic valve endocarditis, particularly in the setting of IV drug abuse, should be considered for routine, serial noninvasive evaluation for the early detection of periannular extension of their infection. PMID- 2582834 TI - Prediction of pulmonary arterial pressure in chronic obstructive pulmonary disease by radionuclide ventriculography. AB - Pulmonary arterial hypertension represents an important parameter for the assessment of the severity of chronic bronchitis. The measurement of the pulmonary arterial pressure, however, requires invasive techniques of limited routine use because of costs and associated risks. The aim of this study is to evaluate whether the 81mKr right ventricular ejection fraction and parameters derived from equilibrium 99mTc red blood cells' right ventricular curve allow a better estimation of PAP than the 99mTc RVEF. In 41 patients with severe chronic bronchitis, the linear correlation between PAP and 99mTc RVEF was -0.61 (p less than 0.001). None of the parameters derived from the right ventricular curve was better correlated to PAP than the 99mTc RVEF. In 16 other chronic bronchitis patients, the 81mKr RVEF correlated moderately to PAP. In conclusion, the alternative isotopic methods proposed in this work do not provide a reliable estimation of pulmonary arterial pressure in patients with chronic bronchitis. PMID- 2582835 TI - Civilian spontaneous pneumothorax. Treatment options and long-term results. AB - The treatment of spontaneous pneumothorax in the civilian population can be influenced by the age of the patient and the presence of associated pulmonary disease. The medical records of 130 patients who presented with 168 occurrences of SP were reviewed during an 11-year period (1973 to 1984). Follow-up was from a minimum of 30 months to 13 years (mean 6.3 years). The therapeutic options included observation alone (40 occurrences), thoracentesis (6 occurrences), chest tube thoracostomy (102 occurrences), and thoracotomy (20 occurrences). Treatment of SP should be prompt with the objective of complete re-expansion of the lung and prevention of recurrent pneumothorax. This should be accomplished by the use of chest tube thoracostomy with early addition of thoracotomy as necessary. Selected use of thoracentesis can be effective. The use of observation alone can be dangerous and is associated with a higher recurrence rate. PMID- 2582836 TI - Demand oxygen delivery for patients with restrictive lung disease. AB - The demand oxygen delivery system has been reported to improve oxygen delivery 7:1 vs steady flow during rest and exercise in COPD patients. The present study evaluates the DODS during rest and exercise in eight patients with restrictive lung disease. It was concluded that the DODS provides substantial oxygen savings in RLD patients, particularly during exercise. PMID- 2582837 TI - Can maximal cardiopulmonary capacity be recognized by a plateau in oxygen uptake? AB - The failure of oxygen uptake to increase with increasing work has been considered a marker of the limits of the cardiopulmonary system for many years. However, the concept has suffered from inconsistencies in definition, criteria, and data sampling, all of which affect the interpretation of the relation between changes in work and oxygen uptake. To evaluate the response and reproducibility of the slope in oxygen uptake at peak exercise, six subjects (mean age, 33 +/- 6 years) performed two individualized ramp treadmill tests on separate days. During exercise, oxygen uptake (for a given sample of 30 eight-breath running averages) was regressed with time and the slope was calculated. Maximal oxygen uptake, maximal heart rate and maximal perceived exertion were reproducible from day 1 to day 2 (mean difference, 0.4 ml/kg/min, 1.0 beats per minute, and 0.2 for maximal oxygen uptake, heart rate, and maximal perceived exertion, respectively [not significant]). Considerable variability in the slopes was observed during each test and from day to day. This occurred despite the use of large gas exchange samples, averaging techniques, and constant, consistent changes in external work. A plateau, defined as the slope of an oxygen uptake sample at peak exercise that did not differ significantly from a slope of zero, was not a consistent finding within subjects between days. We conclude that marked variability in the slope of the change in oxygen uptake occurs throughout progressive exercise, despite the use of large samples and a linear change in external work. These findings appear to preclude the determination of a plateau by common definitions. PMID- 2582838 TI - The cardiovascular effects of inhaled fenoterol alone and during treatment with oral theophylline. AB - We have investigated whether oral theophylline potentiated the cardiovascular effects of fenoterol administered by metered-dose inhaler. Eight healthy subjects were investigated on four occasions. On successive days (1 and 2), the subjects were given doses of 400 micrograms, 600 micrograms, and 800 micrograms of fenoterol at 15-minute intervals (total dose, 1.8 mg) or matched placebo. Systolic time intervals, blood pressure, and the ECG were recorded at baseline and five minutes after each inhalation. Thereafter, the subjects were treated with slow-release theophylline for eight days. On days 9 and 10, the procedures on days 1 and 2 were repeated. The order of treatment was applied according to a crossover Latin-square design. The effects after theophylline alone were no different from placebo. Theophylline potentiated those hemodynamic effects of fenoterol due to enhanced cardiac sympathetic tone (mean +/- SE) as measured by a decrease in Q-S2I (-41.6 +/- 7.6 ms vs -27.3 +/- 5.9 ms; p = 0.0004), an increase in systolic BP (23.5 +/- 2.8 mm Hg vs 9.0 +/- 5.3 mm Hg; p = 0.00001), and an increase in heart rate (15.8 +/- 1.6 bpm vs 9.1 +/- 3.7 bpm; p = 0.0013). The responses mediated by beta 2-adrenergic receptor stimulation, namely, a decrease in PEP and diastolic BP, were not potentiated. Although fenoterol prolonged the Q Tc interval and decreased T-wave amplitude, these effects were not potentiated by theophylline. Oral theophylline potentiates the positively inotropic and chronotropic effects of fenoterol. PMID- 2582839 TI - Pulmonary non-Hodgkin's lymphoma in AIDS. AB - Whereas extralymphatic involvement is common in lymphomas associated with HIV infection, there have been few reports of pulmonary lymphoma. In 648 cases of AIDS reported in Colorado, 40 have had non-Hodgkin's lymphoma. Of these, four have had documented pulmonary involvement and are reported in detail. Clinical manifestations were nonspecific and included fever, weight loss, generalized lymphadenopathy, dyspnea, chest pain and cough. Chest roentgenograms revealed multiple nodules or interstitial infiltrates. Transbronchial biopsy failed to establish the diagnosis in all cases. Three of four patients died four to five months after appearance of pulmonary nodules; one patient with stage IE disease showed slow radiographic progression over 16 months following radiation and chemotherapy and died 18 months after appearance of pulmonary nodules. Pulmonary involvement with lymphoma should be considered in patients with HIV infection, especially if multiple nodules are seen on chest roentgenograms. PMID- 2582840 TI - High frequency of atopic asthma in a pulmonary clinic population. AB - Seventy-two consecutive adult asthmatic patients seen in the Pulmonary Clinic at Rhode Island Hospital were tested for atopy by prick test with 14 standard aeroallergens and by in vitro total and specific IgE determinations (FAST). A total of 58.3 percent of patients were found to be atopic by these tests. There was a significant difference between the mean total serum IgE in atopic and nonatopic asthma and in atopic asthma and control subjects. The age onset was lower in atopic asthmatic patients, and they were more likely to have a history of chronic rhinitis than nonatopic subjects. Family history of rhinitis or asthma and severity of asthma was not different between the two groups. Since our outpatient facility has a large allergy clinic in proximity to the pulmonary clinic, which was the source of our patient population, this investigation has a negative bias toward allergy. Nevertheless, this study reveals that atopy is common in adult asthmatic patients, and a battery of allergy tests (skin tests or in vitro tests) together with total serum IgE is able to differentiate between atopic and nonatopic asthma. PMID- 2582841 TI - The SaO2/t diagram as a useful means to express nocturnal hypoxemia. AB - The computerization of SaO2 recording during polysomnographic monitoring allows the construction of a diagram expressing the percentage of TIB spent at different steps in saturation. We studied the value of this diagram in three groups of male patients: (1) nine healthy subjects (all volunteers); (2) 25 patients with COPD who had a mean daily SaO2 of 92.3 +/- 1.3 percent; and (3) 25 patients with SAS who had a mean daily SaO2 of 92.1 +/- 1.4 percent. The results show the existence of a discriminating quality in the diagram's morphology, the existence of strong correlations (p less than 0.01) between the percentage of TIB spent at SaO2 less than 85 percent, and the total duration of the desaturation dips. PMID- 2582842 TI - Ventilation and breathing pattern during sleep in Duchenne muscular dystrophy. AB - Ventilatory data, including timing and partitioning of ventilation, were obtained from six subjects with advanced Duchenne muscular dystrophy, aged 16 to 22 years, during polysomnography on two consecutive nights; the subjects were randomized to breathing air or oxygen. Five of the six patients developed oxygen desaturation exceeding 5 percent during rapid eye movement (REM) sleep while breathing air. Minute ventilation on air (the mean of at least six consecutive minutes) was 6.9 +/- 0.7 (SEM) L min-1 but fell, owing to decreases in both tidal volume and frequency, to 4.9 +/- 0.3 L min-1 (p less than 0.05) in slow wave sleep and to 4.5 +/- 0.6 L min-1 (p less than 0.05) in REM sleep. Similar falls were seen on oxygen. The variability of all ventilatory data was significantly greater in REM than non-REM (NREM) sleep. The mean abdominal contribution to breathing was lower than predicted for wakefulness and all sleep stages, and two subjects showed paradoxical abdominal movement in NREM sleep; a correlation (p less than 0.05) existed between the NREM abdominal (diaphragmatic) contribution and the extent of oxygen desaturation subsequently seen in REM. We conclude that although awake minute ventilation is normal in Duchenne muscular dystrophy, hypoventilation occurs in all sleep stages, and those with diaphragmatic dysfunction are especially vulnerable to oxygen desaturation during REM sleep. PMID- 2582843 TI - Treatment of lymphangioleiomyomatosis. A meta-analysis. AB - Lymphangioleiomyomatosis is a rare disease which afflicts young women of childbearing age. It is sufficiently uncommon that randomization or any other systematic evaluation of regimens of treatment has been difficult. Review of scattered case reports implies that a number of hormonal manipulations may be equally effective. A comprehensive review of the literature revealed 30 cases of LAM treated with eight regimens of treatment. Evaluation with predetermined criteria (meta-analysis) shows that administration of progesterone or oophorectomy or both are the most effective treatments, resulting in improvement or stabilization of the disease in the majority of cases. PMID- 2582844 TI - Cardiorespiratory effects of pressure controlled inverse ratio ventilation in severe respiratory failure. AB - Cardiorespiratory values were measured in nine patients with severe respiratory failure before and following initiation of pressure controlled inverse ratio ventilation (PC-IRV) at an inspiratory to expiratory ratio of 2:1. All patients showed increases in PaO2, with the mean PaO2 rising from 63 +/- 4 (mean +/- SEM) to 76 +/- 8 mm Hg. Peak inspiratory pressure fell from 44 +/- 4 to 39 +/- 2 cm H2O. There were no significant changes in any hemodynamic or oxygen metabolism variable associated with the institution of PC-IRV. In particular, no significant alteration in cardiac index, pulmonary artery pressures, oxygen delivery, oxygen consumption, or oxygen extraction ratio occurred with the use of PC-IRV. These results suggest that PC-IRV may be a useful ventilatory modality in the treatment of severe respiratory failure since it results in improvement in arterial oxygenation without any deterioration in hemodynamic or tissue oxygen metabolism parameters. PMID- 2582845 TI - Continuous in-line nebulizers complicate pressure support ventilation. AB - Patients ventilated in the pressure support mode must generate a negative airway pressure before the ventilator will deliver a breath. Inserting a continuous-flow nebulizer between the patient and the sensor in the ventilator makes it more difficult for the patient to generate this negative pressure. We observed two mechanically ventilated patients who were unable to initiate ventilator breaths in the pressure support mode while bronchodilators were being administered through a continuous-flow nebulizer. In neither case did ventilator alarms sound. Using a lung model, we found that when the nebulizer flow rate exceeded the mean inspiratory flow rate of the test lung, the negative pressure necessary to trigger the pressure support ventilator could not be generated. Critical care providers need to be aware of this potential complication, since it may lead to serious underventilation of their patients. PMID- 2582846 TI - Respiratory acoustic impedance in left ventricular failure. AB - The measurement of respiratory acoustic impedance (Zrs) by forced pseudorandom noise provides a simple means of assessing respiratory mechanics in nonintubated intensive care patients. To characterize the lung mechanical alterations induced by acute vascular congestion of the lung, Zrs was measured in 14 spontaneously breathing patients hospitalized for acute left ventricular failure. The Zrs data in the cardiac patients were compared with those of 48 semirecumbent normal subjects and those of 23 sitting asthmatic patients during allergen-induced bronchospasm. In the patients with acute left ventricular failure, the Zrs abnormalities noted were an excessive frequency dependence of resistance from 10 to 20 Hz and an abnormally low reactance at all frequencies, abnormalities qualitatively similar to those observed in the asthmatic patients but of lesser magnitude. Acute lung vascular congestion modifies the acoustic impedance of the respiratory system. Reflex-induced bronchospasm might be the main mechanism altering respiratory acoustic impedance in acute left ventricular failure. PMID- 2582847 TI - Analysis of resistance to gas flow in nine adult ventilator circuits. AB - We measured the resistance in nine complete ventilator circuits, partial circuits and 7, 8, and 9 mm ID endotracheal tubes at flow rates of 20 to 120 liters per minute. We found a statistically significant (p less than 0.01) increase in resistive pressure with increases in flow rate, as the diameter of the ETT decreased, and as each component of the ventilator circuit was added to the ETT. There was a curvilinear increase in resistive pressure to increase in flow rate. However, when resistances were computed, the Bennett cascade "circuit" created higher resistance at 20 lpm than at flow rates up to 120 lpm. The Bennett cascade humidifier added the greatest resistive pressure, 3.5 to 8.5 cm H2O, the Engstrom Edith, 0.5 to 6.5 cm H2O, and the Conchapak added the least, 0.0 to 2.5 cm H2O at flow rates of 20 to 120 lpm. After all the components of the ventilator circuit were attached to the ETTs, there was approximately a 97 to 450 percent increase in resistive pressure compared to the resistive pressure created by the ETTs alone. PMID- 2582849 TI - A classic image of complete right main bronchus avulsion. PMID- 2582848 TI - Bilateral focal pulmonary densities. PMID- 2582850 TI - Everything that wheezes is not asthma. A tale of an Indian businessman. PMID- 2582851 TI - Atrioventricular canal associated with trisomy 9. AB - The features of a newborn with the full clinical aspect of trisomy 9 presenting with an atrioventricular canal is described. This association of anomalies has never been reported before. Interestingly, the patient also had a left-sided obstruction which is known to be more characteristically associated with atrioventricular canal without Down's syndrome. PMID- 2582852 TI - Recurrent high-altitude illness associated with right pulmonary artery occlusion from granulomatous mediastinitis. AB - While travelling across the intermountain West at an altitude of approximately 2,300 m, a 35-year-old man developed symptoms of HAPE. Delay in diagnosis and treatment was nearly lethal. Subsequent evaluation demonstrated unilateral pulmonary artery occlusion, presumably resulting from antecedent granulomatous mediastinitis. This case report supports the concept of evaluating anyone developing HAPE at relatively low altitude for an underlying predisposition. PMID- 2582854 TI - A muscle-saving posterolateral thoracotomy incision. AB - A posterolateral thoracotomy incision which spares the latissimus dorsi and serratus anterior muscles and provides adequate exposure for major thoracic procedures and structures in the posterior hilum is described. Preservation of these accessory muscles of respiration results in improved respiratory dynamics, decreased postoperative pain, and early recovery. PMID- 2582853 TI - Yohimbine-induced bronchospasm. AB - Yohimbine is an alpha-2 blocking agent which also increases cholinergic activity. This medication is used to treat male impotence. We report a case of yohimbine induced bronchospasm. PMID- 2582855 TI - Pulmonary involvement in Behcet's syndrome. AB - We present a case of Behcet's syndrome with unusual pulmonary manifestations. A woman presented five years previously with oral, genital and ocular lesions found on biopsy to be consistent with Behcet's syndrome. While on prednisolone, she complained of nonpleuritic chest pain. Clinical features of active Behcet's syndrome were absent. A previously normal chest x-ray film showed multiple intrapulmonary lesions. Laboratory abnormalities were consistent with findings seen in phases of disease activity. Bronchoscopy showed ulceration of the bronchial mucosa, but no evidence of opportunistic infection or neoplasia. Pulmonary angiography excluded vaso-occlusive abnormalities. A provisional diagnosis of pulmonary involvement with Behcet's syndrome was made and the patient responded to further immunosuppressive therapy. PMID- 2582856 TI - Noncardiogenic pulmonary edema following laser therapy of a tracheal neoplasm. AB - Nd-YAG laser phototherapy has been demonstrated to be effective for the treatment of airways obstruction caused by tracheal tumors. Pulmonary edema has been reported as a complication following acute relief of an upper airway obstruction. We describe a case where laser photoresection of an endotracheal malignancy resulted in acute pulmonary edema. It is important to recognize this potential cause of respiratory deterioration following successful phototherapy to obstructing lesions of the upper airways. PMID- 2582857 TI - Cardiac amyloidosis causing ventricular tachycardia. Diagnosis made by endomyocardial biopsy. AB - In patients with malignant ventricular arrhythmias, endomyocardial biopsy may be helpful when all other findings from the workup are negative. A case of nonsustained polymorphic ventricular tachycardia is presented. The findings from an echocardiogram, coronary angiogram, and cardiac catheterization were negative. An electrophysiologic study showed inducible nonsustained ventricular tachycardia. A right ventricular endomyocardial biopsy was diagnostic of cardiac amyloid. The findings from a workup for systemic amyloidosis were negative. Primary cardiac amyloidosis should be considered in patients with malignant arrhythmias and no documented heart disease, and endomyocardial biopsy is helpful in making this diagnosis. PMID- 2582858 TI - Recurrent calcium emboli in a patient with aortic stenosis. AB - We report a patient with moderate aortic stenosis who had two episodes of calcium embolus to the left popliteal artery within ten months. This case suggests that calcium emboli can be recurrent and that major calcium emboli should warrant consideration of valve replacement, even in patients with mild aortic stenosis. PMID- 2582859 TI - Pulmonary amyloidosis with pulmonary arteriovenous fistula. AB - A 77-year-old man was found to have multiple pulmonary amyloidoma and arteriovenous (AV) fistula of the lungs. Massive deposits of amyloid were present in the vascular wall, which apparently caused the fistula. PMID- 2582860 TI - Calcified plaque in the superior portion of the major fissure. An unusual manifestation of asbestos exposure. AB - Parietal pleural plaque is a well-recognized sign of exposure to asbestos. Visceral pleural involvement is an uncommon manifestation, and calcified visceral pleural plaques are rare. Those reported have been in the minor fissure and inferior major fissure. We describe a unique calcified plaque in the superior major fissure. PMID- 2582861 TI - Rapid mucosal absorption of topical lidocaine during bronchoscopy in the presence of oral candidiasis. AB - Local anesthetic agents are topically applied during diagnostic procedures such as bronchoscopy. These routine procedures are associated with only rare reports of drug toxicity or extensive systemic drug absorption. We report a case of rapid systemic absorption and elevated plasma lidocaine concentrations following a fiberoptic bronchoscopy procedure in a man with oral candidiasis and lung cancer. PMID- 2582862 TI - Simple conversion from intravenous aminophylline to twice daily oral theophylline. PMID- 2582863 TI - Primary Sjogren syndrome and pleural effusion. PMID- 2582864 TI - Medical management of hemoptysis. PMID- 2582865 TI - Pneumothorax during bronchoalveolar lavage. PMID- 2582866 TI - Primary biliary cirrhosis and sarcoidosis. PMID- 2582867 TI - Dosages for labetalol. PMID- 2582868 TI - Can we protect children from abuse? A review of three cases. AB - Abused infants at risk of further abuse are not being protected for many reasons. The ability of a variety of professionals to recognize and manage abuse when it occurs is limited. The reasons for this are briefly presented. Three cases in which young infants were reinjured, one fatally, are presented. Continuing efforts to improve all parts of the child welfare system and community response system need to be made. In this way, infants at risk will be better protected in our society. PMID- 2582869 TI - [Medical care orders between need and reality]. PMID- 2582870 TI - [Specialty commentary on fee regulations. EBM (BMA/E-GO) 1987. I. Surgery of the body surface no. 2100-2180]. PMID- 2582872 TI - [Woman physicians in the year 2000: new strategies for managing changing responsibilities in career and personal planning. Females in surgical specialties]. PMID- 2582871 TI - [Physical examinations based on criminal process regulations--exemplified by suspected intracorporeal drug smuggle]. PMID- 2582873 TI - [Clinical management for medical directors and supervisors--is it necessary?]. PMID- 2582874 TI - [Parathyroidectomy and autotransplantation in renal hyperparathyroidism. I. Clinical and chemical laboratory studies following tissue selection]. PMID- 2582875 TI - [Parathyroidectomy and autotransplantation in renal hyperparathyroidism. II. Morphologic and functional studies in transplant-dependent recurrence]. AB - Corresponding to predefined macroscopic criteria indicating morphological and functional characteristics, fragments of a type 1a-gland were used after total parathyroidectomy for auto-transplantation in 16 hemodialyzed patients with drug resistant renal hyperparathyroidism (rHPT). Fragments of a type 1b-gland were used in two, fragments of a type 2-gland in 17 patients, respectively. The clinical and biochemical follow-up three to 84 months postoperatively showed one patient (3%) with graft-dependent hypocalcemia (type 1a-graft) and in two patients (6%) with type 2-grafts histological examinations confirmed graft dependent recurrent hyperparathyroidism. Thus the estimated cumulative success (= normal parathyroid metabolism; Kaplan Meier) was 78 +/- 12% 5 years postoperatively. Comparing the estimated cumulative function rate of type 1a- and type 2-autotransplants, a better course was found in typ 1a-grafts three years postoperatively (Breslow: p = 0.0724; Mantel-Cox: p = 0.0677). The morphological examinations of the removed enlarged fragments of different size (between 0.2 cm and 0.9 cm) showed signs of an expansive, but never invasive growth. The chief and oxyphilic cells were intermixed and arranged in a follicular pattern as in the former glands selected for grafting. Mitoses could be found more often in larger fragments, thus correlating with a tendency to proliferation and a bad in vitro suppressibility. The results of the studies confirm the conclusions of an in vitro study, showing that the diffuse hyperplastic type 1a-parathyroids are most suited for autotransplantation. Glands or gland areas without fat-cells (type 1b) or nodules of type 2-glands which can be identified intraoperatively using a stereomagnifier should not be used. PMID- 2582876 TI - [The effect of arteriovenous fistulas on the metabolism and morphology of striated muscles]. AB - The revascularization of ischemic extremities by retrograde arterial perfusion has been reported in clinical and experimental studies. The effect of retrograde perfusion on hemodynamics and metabolism of skeletal muscle was investigated in 86 rabbits with various types of AV-fistulas. Since blood flow was markedly reduced, levels of energy phosphates (ATP, CP) stabilized on a lower level. In all groups, lactate raised significantly. Focal morphological lesions were seen in all groups in a various degree. A high incidence of thrombosis was found at dissection. Maintenance of blood flow and metabolism after retrograde perfusion seems to be possible on a low level. PMID- 2582877 TI - [Injuries to retroperitoneal arteries in lumbar intervertebral disk surgery]. AB - Retroperitoneal bleeding as a rarely occurring but life-threatening event after lumbar disc surgery is being presented in three cases. Discussion includes necessary steps in establishing the diagnosis for adequate therapy by referring to clinical features with their anatomical background. PMID- 2582878 TI - [Atrial septum rupture following blunt thoracic injury within the scope of polytrauma]. AB - Blunt thoracic trauma is a frequent diagnosis in polytraumatic patients, blunt cardiac trauma a rare finding. Severe cardiac injuries e.g. myocardial rupture normally result in immediate death of the patients. If patients survive a cardiac trauma, it often remains unrecognized. The interval between trauma and diagnosis of cardiac injury can make up several months up to years. This applies in particular for the traumatic atrial septal defect. A case report of a traumatic atrial septal defect with left to right shunting due to blunt thoracic trauma in a young man is presented. To our knowledge this is the second case of a successfully repaired traumatic atrial septal defect in literature. Problems regarding diagnosis of the less commonly observed blunt cardiac traumas are discussed. PMID- 2582879 TI - [Cavernous transformation of the portal vein. A rare cause of mechanical obstructive jaundice]. PMID- 2582880 TI - [Bridging a subtotal ureter necrosis following burn injury by autotransplantation of the kidney and pyelo-cystostomy]. PMID- 2582881 TI - [Current problems from the viewpoint of a leading hospital surgeon]. PMID- 2582882 TI - [Endoscopy in the continuing education of surgeons]. PMID- 2582883 TI - [Knee joint-bridging mounting of the external fixator for the treatment of close to-the-joint fractures and soft tissue lesions]. PMID- 2582884 TI - [Painful groin in athletes--a surgical indication?]. PMID- 2582885 TI - [Criteria for amputation, reconstruction and replantation of extremities in multiple trauma patients]. AB - The paper defines indications for amputation, reconstruction and replantation of severely injured extremities of multiple traumatised patients using the trauma score PTS (Hannover Polytrauma Score) and the fracture grading for open and closed fractures. PMID- 2582886 TI - [Arthroscopic synovectomy using the Neodymium-YAG laser]. AB - Arthroscopic laser synovectomy consists of a mechanical abrasion of the superficial layers followed by a laser devitalization of the basal synovium. The Neodymium-YAG-laser is suitable for this purpose because of its depth of penetration in tissue and the transmission through quartz flexible fibers. In histological in-vivo-studies laser induced changes in the deep synovial layers could be verified. After a total of 50 arthroscopic laser procedures the clinical results of the first 15 laser synovectomies are analyzed in a follow-up period of 6 months. Compared to the preoperative condition the arthroscopic operation resulted in a significant improvement. A reduced hemorrhage is a specific advantage of this technique. Arthroscopic laser synovectomy is as effective as conventional open capsulosynovectomy preserving the advantages of arthroscopic surgery, a reduced morbidity, a low functional impairment and short rehabilitation periods. PMID- 2582887 TI - [Spontaneous and simultaneous bilateral quadriceps ruptures in hyperparathyroidism]. AB - A report of a case of bilateral spontaneous and simultaneous quadriceps tendon ruptures and a review of the world literature is given. Chronic renal failure and its sequelae, hemodialysis and particularly hyperparathyroidism are associated with all such patients under the age of 50. Diagnosis should be made early since primary suture of the tendons is the treatment of choice. PMID- 2582888 TI - [Value of irrigation-suction drainage in the treatment of early infection of joint implants]. AB - The analysis of follow-up examinations on 77 patients at the Endo-Klinik who were treated with suction irrigation drainage for acute postoperative infection after joint replacement surgery during the last 12 years showed a success rate up to a maximum of 60%. The success of this treatment increased, the earlier and more thoroughly it was performed. Only when the suction irrigation drainage is combined with radical excision of infected soft tissue this operation can save the implant and prolong its service life. PMID- 2582889 TI - [The treatment of large sacral and gluteal soft tissue defects following multiple trauma]. PMID- 2582890 TI - [Alternatives to primary forefoot amputation. Experiences with the external minifixator in complicated pressure necrosis]. PMID- 2582891 TI - [Acute pulmonary complications following femoral intramedullary nailing in a patient with multiple trauma]. PMID- 2582892 TI - [Vascularized fibula transfer for preservation of limbs. A report of 21 cases]. PMID- 2582893 TI - [Osteonecrosis following TEP (total endoprosthesis) exchange, intraoperative femur fracture and multiple cerclages]. PMID- 2582894 TI - [An acetabular ring with support screws for the bridging of bony defects in the acetabulum]. PMID- 2582895 TI - [Trauma Management Trainer. Education and training unit for the management of multiple trauma patients]. PMID- 2582896 TI - DNA loop domains in mammalian spermatozoa. AB - The highly condensed and tightly packaged DNA of hamster spermatozoa was found to be organized into topologically constrained DNA loop domains attached at their bases to a nuclear matrix. The loop domains of the sperm nuclei differed from somatic cell loop domains from the same animal in two aspects. Sperm loop domains were 60% smaller than somatic cell loop domains, with an average DNA length of 46 +/- 7 kb in sperm as compared with 76 +/- 11 kb in brain. Secondly, unlike virtually all somatic cell DNA known which is negatively supercoiled, sperm DNA was devoid of detectable supercoiling. The presence of the loop domain structure in the highly condensed DNA of mammalian spermatozoa suggests that this motif is a fundamental aspect of eukaryotic DNA organization. PMID- 2582897 TI - Sequence of centromere separation: separation in a quasi-stable mouse-human somatic cell hybrid. AB - A quasi-stable mouse-human hybrid cell line, HR61, containing between one and ten human chromosomes was analyzed for the sequence of centromere separation. The purpose was to determine which genome of the two initiates centromere separation first. The data clearly indicate that the separation of centromeres of the human genome is not only initiated but is completed before any centromeres from the mouse chromosomes start splitting into daughter units. The information on whether uniparental chromosome loss results from a lack of deposition of kinetochore proteins was equivocal. The human genome also completes its DNA replication before the mouse genome does. Our studies, therefore, show that the timing of centromere separation is tightly linked to the completion of replication of DNA. At least in this cell line the segregant genome is not the one which exhibits delayed DNA replication. PMID- 2582899 TI - [Coronary arteriography in coronary heart diseases with angina pectoris (an analysis of 55 cases)]. AB - A retrospective study of the coronary arteriographic findings in 55 cases with angina pectoris, 10 spontaneous angina and 45 effort angina (unstable angina 21, stable 24) was presented in the present article. Among the 10 cases with spontaneous angina, 8 showed normal coronary arteries, 2 with double vessel disease. In the 45 cases with effort angina, single and multiple vessel disease was found in 9/45 (20%) and 33/45 (73.3%) respectively, the remaining 3/45 (6.7%) were normal. There was no significant difference in severity and distribution of coronary atherosclerotic lesion (P greater than 0.05) in the two subgroups of unstable and stable angina. However in 3 out of 21 cases (14%) with unstable angina total occlusion of coronary arteries was found suggesting the presence of intracoronary thrombus. Triple vessel disease or/and left main coronary artery lesion was observed more frequently in cases with unstable angina (13/21, 61.9%) than in cases with stable angina (10/24, 41.7%). PMID- 2582900 TI - [Imaging diagnosis of intracardiac myxoma (report of 23 cases)]. AB - The diagnostic imaging manifestations of 23 cases of intracardiac myxoma were analyzed, 22 were confirmed by operation and pathology. In this series the myxoma occurred in left atrium in 18 cases, right atrium 3 and right ventricle 2 cases. Evaluation was made on CT and 2-D echocardiography in the diagnosis of intracardiac myxoma, CT as well as sonography can display clearly the contour and location of the tumor and also its motion with blood flow thereby providing reliable evidence for diagnosis and surgery. CT is superior in differentiating intracardiac thrombus and lipoma from myxoma. PMID- 2582901 TI - [The roentgenologic diagnosis of cor triatriatum sinistrum]. AB - Varied in compliance with the presence and size of the septal foramen, existence and location of the atrial shunt and abnormal pulmonary venous connection, the haemodynamic status of the reported 10 cases of cor triatriatum sinistrum might be classified into four types: Pulmonary venous hypertensive, polyemic, cyanotic polyemic and normal. Accordingly, the roentgenologic features of this anomaly manifested differently and mimicked mitral stenosis or atrial septal defect. PMID- 2582898 TI - DNA denaturation for ultrastructural banding and the mechanism underlying the fluorochrome-photolysis-Giemsa technique studied with anti-5-bromodeoxyuridine antibodies. AB - G- and R-bands produced by an immunochemical approach were studied by electron microscopy (EM) to evaluate the role of DNA denaturation on banding quality. Excellent banding was observed only after adequate denaturation by HCl, NaOH and formamide, used in appropriate concentrations to provide uniform 5 bromodeoxyuridine (BrdUrd) exposure by generating single-stranded DNA. Formamide treatment resulted in less intercellular variability. High temperature and high concentrations of NaOH and HCl altered chromosomal morphology. Besides formamide, Hoechst 33258 prestaining which does not interfere with the binding of the anti BrdUrd antibody and UV irradiation associated with formamide also produced high quality banding. On the other hand, consecutive Hoechst and UV treatment completely inhibited the immunochemical banding. The data indicate that Hoechst and UV act synergistically to disintegrate BrdUrd-substituted chromatin from which DNA is then extracted, leaving only the unsubstituted DNA stainable with Giemsa. PMID- 2582903 TI - [Investigation on the complications in bronchial artery infusion with chemotherapeutic agent to treat bronchogenic carcinoma]. AB - This article reported 797 bronchial arteriography and bronchial artery infusion using CDDP, MMC or 5-FU, in 200 patients with bronchogenic carcinoma. There were 10 patients who had severe complications (1.25%) including: large hematoma (one case), massive hemorrhage (one case), guide wire snapped broken in lumbar artery (one case), thrombosis of femoral artery (one case) and damage of radicular artery of spinal cord (six cases). The causes of complications were discussed. PMID- 2582902 TI - [X-ray diagnosis of non-lymphomatous lymphoid disorders of the chest]. AB - The non-lymphomatous lymphoid disorders of the chest are rare conditions characterized by infiltration of the pulmonary interstitium with lymphocytes and plasma cells. This article reported 6 pathologically proved cases, including Castleman's disease (3), pseudolymphoma (1), angioimmunoblastic lymphadenopathy (1), and lymphomatoid granulomatosis (1). The X-ray findings of these lesions were rather characteristic. In our series, the chest film showed large patchy areas of consolidation sometimes with the presence of air bronchogram in pseudolymphoma and lymphomatoid granulomatosis, simulating bronchiolo-alveolar carcinoma or pulmonary lymphoma roentgenologically. However, the former developed very slowly with little clinical symptoms. Most of the Castleman's disease in this series were found in young adults showing conspicuous, sharply marginated mediastinal node enlargement. Recognition of the aforementioned signs would bring about greater diagnostic accuracy. PMID- 2582904 TI - [Exogenous allergic alveolitis--a clinico-radiologic analysis of 15 cases of pigeon breeder's lung]. AB - A clinico-radiologic analysis of 15 cases with exogenous allergic alveolitis in pigeon breeders was reported. There were 4 male and 11 female. The age ranged from 15-68 years, averaging 33.5 years. All cases had history of intimate contact with pigeons. The clinical manifestations were dry cough, dyspnea and Velcro's rales at the base of the lung. The X-ray appearances included increased, coarsened, tortuous and hazy lung markings, reticular shadows, ground glass appearance due to decreased lung lucency, patchy shadows and honeycombed areas of lucency etc. These findings however were nonspecific, and must be differentiated from other diseases. Therefore X-ray signs must be closely correlated with clinical picture before making the diagnosis. PMID- 2582905 TI - [CT diagnosis of myasthenia gravis]. AB - This paper reported 21 cases of myasthenia gravis. All investigated by laboratory tests, conventional chest X-ray study and CT scan, and documented by surgery and pathology. There were 9 cases of thymoma, 2 thymic cyst, 8 normal thymus, 1 atrophic thymus and 1 thymic hyperplasia. In this series, the diagnostic accuracy rate of CT scan was over 90%. Of course, CT is a highly efficient technique for evaluation of abnormalities of thymus, but high resolution CT scanner and the ability of correct interpretation of CT image are even more important. PMID- 2582906 TI - [Phlebographic observations on the morphology and function of the femoral vein and its valves]. AB - The morphology and function of the femoral vein and its valves in normal and abnormal groups were analysed and compared in 334 cases (414 lower limbs) by ascending and descending phlebography. The diagnostic criteria were established in the normal and abnormal femoral vein and its valves using statistical analysis. Three types of the femoral valvular incompetence were proposed and the value of ascending and descending phlebography in the diagnosis of femoral valves was discussed. PMID- 2582908 TI - [X-ray diagnosis of primary rhabdomyosarcoma of long bone (report of 4 cases)]. AB - Four cases of primary rhabdomyosarcoma of long bone were reported, all confirmed by operation and pathology. There were 3 male and 1 female. The femur was involved in 1 case and tibia in 3. Based on the radiologic manifestations the tumor could be divided into two different types: (1) Osteolytic form: Presenting as large area of osteolytic destruction without periosteal reaction; (2) Mixed form: In addition to patchy osteolytic destruction, calcification or dense tumor bone in the medullary cavity or soft tissue can be seen, often associated with periosteal reaction. PMID- 2582907 TI - [The roentgen findings and pathological basis of parosteal osteosarcoma]. AB - The roentgen findings of 17 cases of parosteal osteosarcoma were analyzed. In 13 of them, a patho-radiologic correlative study was conducted. The results showed that there was an obvious relationship between the radiologic pattern and the degree of malignancy. On roentgenogram, tumor with dense ivory bone as the main manifestation is mostly lower in malignancy, while cotton-like and spiculate tumor bone usually denotes higher degree of malignancy. The pathological basis of the radiolucent area inside the tumor, the satellite nodules in the vicinity of the tumor as well as the differential diagnosis were discussed. PMID- 2582909 TI - [Some problems concerning the radiologic diagnosis of eosinophilic granuloma of the bone]. AB - 125 eosinophilic granulomas of the bone in 61 cases were reported. The radiologic manifestations may be summarized as follows: (1) Multiple lesions may occur with vertebra plana; (2) Epiphyseal lesion may be primary or secondarily involved by extension from metaphyseal lesion; (3) Metaphyseal lesion usually presents as an eccentric cystic area or central oval area of lucency; (4) The diaphyseal lesion manifests a "hole within hole" appearance; (5) The tarsal bone may exhibit a "bone within bone" sign; (6) Periosteal Codman triangle may be present. PMID- 2582911 TI - [Magnification radiography with Circlex 0.1 mm ultra-microfocus]. AB - 929 magnification radiographies of different rates of magnification were taken in 719 patients and 39 animals with the Japanese Circlex 0.1 mm ultra-microfocus tube. According to IEC 336/1982 documentation, tests on focus size, resolution, filtration effect of penumbra, filtration effect of contrast, background dispersion and space effect were done. The results showed that 0.1 mm ultra microfocus could produce images of high quality. PMID- 2582910 TI - [Clinical and radiological diagnosis of Fanconi's anemia]. AB - This paper reported 4 cases of Fanconi's anemia, which is a rare disease usually seen in children under 10 years of age. Its clinical features comprise familial pancytopenia, hypoplasia of bone marrow, and conspicuous megakaryophthisis, with multiple malformations predominantly occurring in the skeleton and kidney. Some cases may be associated with abnormalities of the chromosome. PMID- 2582912 TI - [CT, radiologic and pathologic correlative study of pulmonary edema and respiratory distress syndrome in animal model]. AB - Animal models of cardiogenic edema, overhydration edema and respiratory distress syndrome (RDS) were established in 12 rabbits, radiography and CT of the chest were taken in supine position and compared with pathology. In cardiogenic and overhydration edema, the lesion is located at the posterior part of the lungs and around the hili both on CT image and the pathologic specimen. On the radiograph the lesion was projected onto the middle and inner zones of the lungs. In RDS, both CT and pathology showed that the peripheral and posterior parts of the lungs were involved, while on radiograph, the hazy shadows were situated at the periphery of the lungs or in a diffuse pattern. The authors were of the opinion that CT can demonstrate the lesions more clearly than radiography. The underlying mechanism for different distribution of lesions in pulmonary edema and RDS was discussed. PMID- 2582913 TI - [The penetration of cephalosporins across the blood-brain barrier and its clinical significance]. AB - The penetration of Cefuroxime (CXM), Ceftazidime (CTZ), Cefotaxime (CTX), Ceftizoxime (CZX), and Ceftriaxone (CTRX) across the blood-brain barrier was studied in 119 patients with or without meningitis after an intravenous injection of 2 grams. Cephalosporins were undetectable or their concentrations very low in the cerebrospinal fluid (CSF), when there was no inflammation in the meninges. On the contrary, the mean CSF concentrations of cephalosporins were 2.21-5.36 micrograms/ml and the CSF/serum ratios 3.73-31.80% in acute stage of purulent meningitis. The CSF levels of all the five cephalosporins were much higher than the mean MICs of the common pathogens of bacterial meningitis as well as that of Enterobacteriaceae. It is thus shown that these five new cephalosporins are useful for treatment of meningitis including those caused by gram-negative bacilli. PMID- 2582914 TI - [Effect of respiratory failure on water and sodium metabolism]. AB - Water and sodium loading tests were undertaken in 27 cases of cor pulmonale with acute exacerbation. The results showed that ratio of 2 hour urine volume versus water load was 23- +/- 1.38% in respiratory failure (RF) group (17 cases), which was significantly lower than that of non-RF group (10 cases) 51.3 +/- 4.17%, (P less than 0.01) and control group (7 cases) 57.4 +/- 6.54%, (P less than 0.01); ratio of 4-hour urine sodium versus sodium load was 12.0 +/- 1.48% in RF group, which was also lower than that of non-RF group (29.6 +/- 1.93%, P less than 0.01) and control group (30.4 +/- 2.42%, P less than 0.01). It was suggested that excretions of water and sodium decreased in RF group. The incidences of hyponatremia and hyposmosemia were 47.1% and 64.7% respectively in RF group in 6 cases of RF with edema, the excretions of water and sodium increased after oxygen treatment. The mechanism and the clinical significance of hyponatremia and hyposmosemia and of impaired excretions of water and sodium in RF patients were discussed preliminarily. It is concluded that hypoxemia is one of the important causes of the disturbance in water and sodium metabolism. PMID- 2582916 TI - [Abnormality of T cell subsets in patients with idiopathic thrombocytopenic purpura]. AB - Fifty patients with idiopathic thrombocytopenic purpura (ITP) and 50 normal controls were studied for T cell subsets using OKT monoclonal antibodies. These patients were found to have lower proportions of OKT4+ subset and higher proportions of OKT8+ ratio than the healthy controls. The perturbation was more severe in patients with active disease. A significant increase of OKT 4+8+ double labelled cells deduced by a subtraction method was also observed in the peripheral blood of patients and an inverse correlation was demonstrated between the proportions of OKT4+8+ subset and the platelet counts. Furthermore, a positive correlation between the proportions of OKT4-8+ subset and the platelet counts was also found in patients with active ITP. These data suggest that abnormalities of T cell subsets in the peripheral blood may play an important role in the pathogenesis of ITP. PMID- 2582915 TI - [Primary nephrotic syndrome treated with urokinase--a report of 20 cases]. AB - Twenty cases of primary nephrotic syndrome were treated with urokinase at a dosage of 60,000 units per day for two successive weeks. The results showed that after treatment the concentrations of fibrinogen, urine FDP, alpha 2-plasma inhibitor and plasminogen were significantly decreased (P value less than 0.01, less than 0.01, less than 0.001, less than 0.005 respectively). The concentration of antithrombin III was significantly increased (P less than 0.05). It is suggested that the treatment obviously increased the fibrinolytic activity and improved the hypercoagulated state. The clinical data showed that in addition to decrease of proteinuria and obvious increase of urine volume, the clinical manifestations and laboratory parameters showed no significant difference. Further study on the dosage and indications of urokinase is needed and the activity of coagulation and fibrinolysis in patients with deep vein thrombosis of lower extremities was also discussed. PMID- 2582917 TI - [Preliminary report on the clinical application of anti-Jo-1 antibody]. AB - Jo-1 antigen was purified from the rabbit thymus acetone powder. Using it as antigen, we found anti-Jo-1 antibody in 25% of polymyositis, 7.1% in dermatomyositis, none in other connective tissue diseases nor non-connective tissue diseases. Other antinuclear antibodies, eg anti-RNP, anti-SSA were also found in our polymyositis-dermatomyositis patients. Our study suggested, the positivity of anti-Jo 1 antibody not only confirmed the patient's diagnosis of polymyositis but also demonstrated the autoimmune pathogenesis of this disease. PMID- 2582918 TI - [A preliminary study on response to hepatitis B vaccine in subjects with various levels of antibody to hepatitis B surface antigen]. AB - After hepatitis B vaccine immunization, serum antibody response was of primary type in 33 cases with anti-HBs less than 2.1 S/N (S/N Ratio Unit) at T0, the anti HBs positive rate was 39.4%, 84.8%, 96.7% and 96.7% in T1, T2, T0 and T12 respectively. Anti-HBs S/N rose gradually month by month, the antibody response in younger children was better than that in adult. Anamnestic type in 38 cases with anti-HBs greater than 2.1 S/N at T0, the antibody levels rose rapidly in T1, T2 and began to fall in T8. The children were negative for HBsAg, anti-HBs and anti-HBc in sera by RPHA, PHA and ELISA respectively, most (100% in 1-4 age group and 63.2% in 5-9 age group) of them were also negative for HBV serological markers by SPRIA repeatedly, thus they were susceptible and need for hepatitis B vaccine immunization. Indication of hepatitis B vaccination for adult population was also discussed. PMID- 2582919 TI - [Family clustering analysis of HBV infection]. AB - A family clustering analysis of HBsAg, anti-HBs, anti-HBc positive and total infected persons in 148 families on a farm was carried out by the methods of G statistic, binomial distribution and negative binomial distribution. The results consistently showed that there was significant clustering of HBsAg carriers in families, whereas there were not clustering was seen an overall HBV infected persons in families. The clustering of HBsAg carriers in families is due probably to the effect of some genetic factors. The results of G statistic analysis indicate that anti-HBc also have significant clustering in families. PMID- 2582920 TI - [Cadmium exposure and health effects among residents in irrigation area with ore dressing wastewater]. AB - About 0.05 mg Cd/L was found in the irrigation water contaminated by the wastewater discharged from the wolfram ore dressing plants, and about 1 mg Cd/kg was found in irrigated acid soil. The main sources of the cadmium intake by residents, living in pollution areas, were agricultural products. The average intake of cadmium was 366.7-381.9 micrograms/d, smokers 416.6 micrograms/d. Among residents, who have been exposed to cadmium for more than 25 years, cadmium absorption (CdU greater than or equal to 10 micrograms/g Cre) was 60% and early effect of target organ (CdU greater than or equal to 15 micrograms/g Cre and beta 2 -mU greater than or equal to 500 micrograms/g Cre) was 17%. Levels of CdU and CdB were beyond the critical value in the observation areas. The concentrations of CaU, beta 2-mU and NAGU were significantly higher among residents in observation areas compared with control areas. Owing to the combined cadmium effect the cases with fractional beta 2-m excretion greater than 0.10 were 46% in the observation areas, and it was much higher than that in control areas (20.3%) in a case-control study among residents who have been suffering from an original nephropathy with tubulo-interstitial abnormalities. PMID- 2582921 TI - [Bacteriologic investigation of the hospital air-conditioning water]. AB - We have isolated a pathogenic strain of LDB from the water of the hospital cooling-water storage tank for air-conditioning system. At the same time, other bacteria were also isolated with Pseudomonas and Flavobacterium being predominant, most of these organisms in the water of air-conditioning system were resistant to antibacterial drugs. A proposal to improve architectural design and to sterilize air-conditioning water was suggested. PMID- 2582922 TI - [Risk assessment of factors related to lactation of breast-feeding women by multichotomous logistic regression with stepwise procedure]. AB - Based on Dubin and Pasternack's solution of parsimonious parameters, the authors proposed a procedure of stepwise selection of factors for establishing the Multichotomous logistic regression "best" model. Score statistic was used to select factors into model. Ratio of likelihood function was used to eliminate factors from model. The data of lactation from 129 breast-feeding women living in rural area have been analysed by the procedure. It showed that the first breast feeding to the newborn of over 48 hours from her childbirth has negative effect while good appetite has positive effect on milk secretion. The epidemiological meaning of parameters estimated from the data was illustrated in detail. PMID- 2582923 TI - [Confidence factors-method for estimating the confidence limits of standardized population rate of indirect method]. AB - The standardized rate of indirect method is widely used, but no method of interval estimation for its population rate has been reported. The authors have discussed the standard error of standardized rate of indirect method and suggested that a method using this standard error should be used to determine the confidence limits for the population rate. In this paper, the authors put forward another method (Confidence Factors-Method) which can be easily applied to determine the confidence limits. It gives approximately the same result with the method mentioned above. PMID- 2582924 TI - [Measurement of the biochemical marker of smoking: urinary nicotine metabolites]. AB - A novel, barbituric acid method of detecting urinary nicotine metabolites was evaluated for use as an objective test of smoking. Urine samples were collected from 289 male smokers and 167 male nonsmokers. The smokers recorded the number of cigarettes smoked on the previous day. This method correctly classified the subjects as smokers or nonsmokers. There was a significant positive correlation (r = 0.587, P less than 0.001) between the urinary nicotine metabolites/creatinine ratios and number of cigarettes smoked. This method can be performed very rapidly and reagent costs are very cheap. It is a good objective test of smoking and nicotine intake. PMID- 2582925 TI - [Research on the anti-mutagenic effect of six natural foods]. AB - Six natural foods were tested with Ames Test for their anti-mutagenic effect on 2 AF, AFTB, MNNG, NaN3 induced mutagenic activity in TA99 and TA100. The tested substances were extracted repeatedly with acetone. The revertants induced by 2-AF AFTB1 (with TA98, TA100). MNNG (with TA100) were significantly decreased when the six natural foods were added to the medium. The results revealed that all six natural foods showed remarkable inhibitory effect on 2-AF, AFTB1, MNNG induced mutagenic activity for strains TA98 and TA100 and suggested the presence of anti mutagenic substances in the six natural foods. This experiment provides a scientific basis to the study of food substances for the prevention of carcinogenesis. It is considered that the six natural foods possess remarkable anti-mutagenic effect and is practically valuable in the field of chemoprophylaxis of Cancer in men. PMID- 2582926 TI - [A study on the effects of alcoholic beverage on experimental animal behaviors]. AB - Mice and pregnant Wistar rats were given alcoholic beverage at different concentrations. A set of behavioral tests was used to observe the effects on the development and the behavioral functions of the offspring. The retardation of behavioral development and the adverse effects on the learning and locomotor activity of the offspring were observed at highest concentration (60% 10 ml/kg B. W). No similar effects were found at lower concentrations. It is therefore suggested that pregnant women should avoid drinking, in particular, heavy drinking of alcoholic beverage so as to protect the offsprings from adverse effects. PMID- 2582927 TI - [Selective accumulation of 147Pm in organism on induction of micronucleus and SCE of bone marrow cells as well as the mutagenic effect on fetal liver and spleen]. AB - Study of accumulation peculiarity of 147Pm showed that iv. different doses of 147Pm were the same selectively localized in skeleton. Retention of 147Pm in skeleton was elevated when the radioactive doses of 147Pm were increased. At the same time absorption dose of 147Pm radiation was also raised. The ability of 147Pm to induce sister chromatid exchanges (SCEs) has been investigated by IdU labelling methods. A statistically significant elevation of SCEs was observed after 147Pm intake. The number of SCEs per cell in bone marrow cells was always higher in mice when the animals were maintained on the doses of 37 Bq/g. We observed the injurious effects of 147Pm, using micronucleus rates in bone marrow cells as indicator. The results showed that the lower limit of injected activity effecting marked rise of rates was 185 Bq/g A peak rate of 1.34% was reached at 24 here after intake of 147Pm 1.85 x 10(5) Bq/g. Our study is also to ascertain the correlation between maternal deposition, perinatal uptake of 147Pm and their chromosome aberrations of maternal and fetal liver cells. Results indicated that 147Pm was predominantly deposited in maternal liver. Deposition of 147Pm in maternal spleen was about one quarter of that in the maternal liver. In view of the placental barrier uptake of 147Pm by fetal liver or spleen was definitely depressed. Studies indicated that maternal contamination of 147Pm could induce chromosome aberrations in fetal liver and spleen cells. Among the type of aberrations induced by 147Pm, chromatid breakage were predominant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2582928 TI - [Anteversion angle of the femoral neck in congenital dislocation of the hip]. AB - The anteversion angle of femoral neck in 40 children, aged 18 months to 14 years (4.6 years on average), with congenital dislocation of hip was measured pre operatively on X-ray films according to the way of Dr. Hu's method, and from the proximal femur exposed during operation. The mean value of them was 64.6 degrees and 44 degrees respectively, being statistically significant (P less than 0.01). The method of direct measurement of the anteversion angle during operation was described. The factors affecting the diversity of the measured angle value with different methods were discussed. It seems that the calculation formula used in Hu's method should somehow be corrected and a revision is put forward. PMID- 2582929 TI - [Central fracture-dislocation of the hip joint. Clinical analysis of 40 cases]. AB - From 1957 to 1986, 40 cases of central fracture-dislocation of hip joint, 36 fresh and 4 old, were treated. Classification concerning the lesional patterns, indications for operative and non-operative treatment together with the factors affecting prognosis were discussed. In conclusion firstly, treatment by means of traction, simple and easy to handle, is well suited to most cases, if reduction has been satisfactory and maintained well, permitting early motion, for sufficient period of time for healing. Secondly, operation is only fit for fracture-dislocation, of which reduction has not been good enough and that it would not subject the patient to much surgical risk. Lastly, poor reduction, traction time not long enough, accetabular roof fracture or femoral head fracture and extensive damage or concomitant fracture of the same limb are the recessive factors influencing outcome. PMID- 2582930 TI - [Entrapment of the synovium of the hip joint in children: a report of 15 cases]. AB - 15 cases, aged 4 to 14 years, experienced, a few days after a mild trauma, slight pain and limited motion of hip joint with the corresponding leg lengthened, a result of restrained adduction. Plane X-ray films of these hip joints showed nothing wrong, yet arthrography done on 4 cases and operative exploration in 1 patient found that a portion of synovium at the anteromedio-inferior part of the hip had been entrapped into the joint, on account of which the term entrapment of synovium of hip joint is coined. Under general anesthesia, gentle manipulation resulted in immediate relief in all hips but one, which failed to respond and then under went open operation, a very good chance of looking into the matter: a big portion of synovium incarcerated in the joint, the actual offender. There has been no recurrence found up to the time of writing. The pathogenesis and the related differential diagnosis have been discussed in detail. PMID- 2582931 TI - [Double-cup replacement in the treatment of tuberculosis of the hip. Long-term follow-up studies]. AB - 24 tuberculous hip joints were treated by radical debridement and double-cup replacement in one single stage. They healed up primarily and remained well up to the time of follow-up, a period of 5 years and 7 months on average, except one which recurred 1 month after operation and persisted until removal of the implants. Slipping of head cup occurred in 4 cases in 10 to 12 months post operatively. The slipped cups were removed or received, showing fibrous drinking of the head stump. Factors influencing and the time taking place of slipping of head cup along with it management were discussed and described. It is shown that radical debridement and double-cup replacement could serve to cure the tuberculosis and preserve the function of the hip joint. PMID- 2582933 TI - [Influence of calcar femoral on stress distribution of the upper femur and its clinical application]. AB - Relation between the integrity of the internal structure of upper femur and femoral neck fracture was investigated by means of photo-electric technique. It was found that the stress increased significantly in the upper femur when its calcar femoral was defective, and that the nearer the defective area to the femoral head the greater was the stress. This increased stress was especially significant at the heel strike period of stance phase during walking. As a result of osteoporosis and deficit of the calcar femoral in the elderly, upper femur fracture, mostly subcapital or transcervical type is commonly seen in the aged. The feasibility and principle of internal fixation with thread-screw pins for subcapital and transcervical fracture have been discussed in conjunction with the distribution of tensile and compressive stresses. PMID- 2582932 TI - [Surgical treatment of intertrochanteric fracture]. AB - 75 cases of intertrochanteric fracture were treated operatively with different instrumentation according to the fracture patterns. Classification of these fractures in relation to choice of fixation device used were discussed. We are in favour of dividing these fractures into two types: stable, 31 fractures; 24 of them were fixed with compression screws, the rest 7 with compression sliding lag screw-plate; unstable, 44 fractures; they were fixed with compression sliding lag screw-plate except 6. Follow-up, average 1 year and 9 months, showed normal joint function in 64 cases (85%) and walking with crutches in 8 (10.8%). PMID- 2582935 TI - [Stone formation and amino acid analysis of glycoproteins of gallstones]. AB - On the basis of amino-acid analysis of glycoprotein extracts from human pigment and cholesterol stones, we came to the conclusion that it was not collagen, reticulin, nor elastin or fibroprotein but most likely to be the precursor of collagenic polypeptide. It was postulated that in acid circumstances the precipitated collagenic polypeptide with positive charges on its surface acts as nucleus of stone to combine with negative charged acid polysaccharide, the glycoprotein thus formed further combines with negative charged pigment and/or cholesterol into crystals in the process of stone formation. PMID- 2582934 TI - [Diagnosis and treatment of idiopathic necrosis of the femoral head]. AB - Fourteen cases, 25 hips, of idiopathic necrosis of femoral head (INFH) were included in our series. The role of radiographs, isotopic bone scanning, intraosseous pressure measurement and intraosseous venography in diagnosis of INFH was evaluated. Radiological examination cannot reveal early case, while isotopic bone scanning was more sensitive. There was increase of intraosseous pressure in most diseased hips. Intraosseous venography was abnormal in all examined hips. These two tests could therefore detect early INFH. Core decompression was performed on 21 hips. The operated hips were followed for 3.5 months to 20 months. Functional evaluation of 18 hips were good or excellent. Radiographic re-examination of 20 hips remained unchanged. The postoperative intraosseous pressure measurement and intraosseous venography in examined hips revealed a decrease of intraosseous pressure and improvement of venous drainage. Core decompression is therefore an ideal method of treatment for early INFH. PMID- 2582936 TI - [Effect of splenectomy on phagocytic function of leucocytes]. AB - By means of whole blood chemiluminescence, phagocytic function of leucocytes (PFL) and the opsonic activity of plasma (OAP) were examined in 27 patients to observe the effect of splenectomy on phagocytic function of leucocytes. It was found that, the PFL of splenectomized patients was significantly lower than that of healthy persons and patients with cholecystectomy. It was then believed that the impaired immunological function against infection in splenectomized patients was related to the abnormal PFL resulting from the disappearance of tuftsin in the circulation, an important leucocytic activator produced only in the spleen. It was showed in this paper that the whole blood chemiluminescence is a simple, rapid and useful method in detecting PFL and OAP. PMID- 2582937 TI - [Clinical treatment of traumatic false aneurysm and arteriovenous fistula]. AB - In this article, treatment of 41 cases of traumatic false aneurysms and arteriovenous fistulas are reported. The methods consist of arterial ligation in 6 cases, end-to-end anastomosis in 5 cases, prosthesis or autogenous vein grafts in 9 cases, "Flying Kite" technique by muscular embolism in 5 cases, vascular embolism by means of the spring-coil in 14 cases, direct operation combined with vascular embolism in 1 case, and breaking blood stream by the balloon catheter at first, then embolism by the spring-coil through retrograde catheterization and finally removal of false aneurysm in 1 case. Indications and advantages of the varied methods are discussed. PMID- 2582938 TI - [Traumatic diaphragmatic injury and hernia]. AB - 31 cases of traumatic diaphragmatic injury were treated in our department from Jan. 1977 to Jan. 1986. Among them, 18 were caused by blunt trauma and 13 by penetrated wound. 17 of the cases accompanied with diaphragmatic hernia. 80% of the cases (25/31) were complicated trauma. As a result, 28 of them recovered with only 3 died. The authors described the mechanism and characteristics of diaphragmatic trauma as well as its diagnosis and treatment. PMID- 2582940 TI - [Technic of esophagogastrostomy using intraluminal elastic circular ligation. Clinical analysis of 100 cases]. AB - The results of 100 cases of carcinomas of esophagus and gastric cardia by resection and intraluminal elastic circular ligation was reported. The operation method and analysis of the results of the treatment are discussed. The authors suggest that it may be better if the supporting tube made by absorbable material. PMID- 2582939 TI - [Open mitral valvuloplasty under cardiopulmonary bypass. Report of 24 cases]. AB - 24 cases of open mitral-valvuloplasty were reported. The clinical date are back from October 1980 to July 1987. Operative technique, indication and contraindication are discussed. By preserving autovalvular tissue in site, some complications and the deterioration of the artificial valves can be avoided. One patient died postoperatively. The survivals were followed-up 3 months to 6.5 years (average 3.1 years). The authors considered that careful selection of patients, myocardial protection, and accurate manipulation of the operation are important factors of success. PMID- 2582941 TI - [An evaluation of lymphangiography in the diagnosis of nodal metastasis from genitourinary cancer]. AB - From September 1979 to March 1988, lymphangiography was carried out in 187 cases of genito-urinary cancers and the specific features of metastatic lymph-nodes have been summarized. The results showed that the false positive was much lower in bladder, testicular, and prostatic cancers than in penile cancer. In order to enhance visualization of the pelvic, lumbar and kidney-hilar nodes, a combined lymphangiography should be done through both bipedal and funicular routes. A percutaneous FNAB is necessary to minimize the false positive. PMID- 2582942 TI - [Experimental study on the bone cement-precoated implant in arthroplasty]. AB - Canine hip joints, in vitro and in vivo, were used for arthroplasty: one side was replaced by a bone cement-precoated femoral head prosthesis and the other side by a non-cement-precoated one. Results showed that the interfacial shearing strength between both the implant-cement and the cement-bone interfaces of the cement precoated ones was obviously stronger than that of the non-cement-precoated ones. Thus, the stability of the prosthesis was remarkably increased in the former than the later. PMID- 2582943 TI - [An analytical study of optical conditions of the elderly]. AB - The visual acuity, refraction and related factors in 471 eyes 60-90 years of age were analyzed with the authors's statistical method for refractive data. The mean logarithmic visual acuity (Lv) of all eyes naked was 4.66 (equivalent to 20/44, or 6/13), and with corrections 5.03 (equivalent to 20/18.7, or 6/5.6). There was significant negative linear correlation between Lv and age (r = -0.9684), Lv = 5.7183-0.0095 x age. The percentages of hyperopia and myopia in the series were 47.8% and 39.7%, the mean refraction being +0.96 DS +0.78 DC and -1.29 DS -0.95 DC respectively. The percentage of mixed astigmatism was 7.86%, averaging +0.71 DC -0.74 DC. The mean refraction of all the patients was -0.05 +/- 2.90 DS -0.04 +/- 1.14 DC. PMID- 2582944 TI - [Retinal function test of eyes with opaque refractive media]. AB - The characteristics of the laser interference fringes of opaque lenses were studied by the laser speckle method. After studies with the opaque lenses in the laboratory, the method was employed in the clinic. The preoperative laser interference fringe visual acuities were compared with the postoperative corrected visual acuities in 65 eyes with mature cataract and 8 eyes with cornea opacities. The authors concluded that the laser speckle interferometry estimated the retinal function of eyes with opaque refractive media quantitatively and it demonstrated practical value in the clinic. PMID- 2582945 TI - [A pattern-ERG study of amblyopia]. AB - 26 normal and 60 amblyopic children were examined with the P-ERG. The results showed that P-ERG in amblyopes was significantly abnormal, with delay in the latent periods of wave b and the after potential, as well as reduction in the amplitudes of the same. The latency of wave a was also delayed in some severe amblyopes. The abnormal manifestations of P-ERG and the mechanism in their occurrence were discussed. The P-ERG could be a sensitive and objective diagnostic method for amblyopia. PMID- 2582946 TI - [Further studies on the functional decompensation of corneal endothelial cells]. AB - 30 cases of corneal endothelial decompensation occurred in 241 transparent grafts of penetrating keratoplasty during a 5-year follow-up with the specular photomicroscope. The study indicated that the critical cell density for corneal endothelial decompensation was 786/mm2; the critical cell dimension as represented by the sum of mean maximal and minimal diagonal was 35.43 microns; and the critical difference between the mean maximal and minimal diagonal was 14.70 microns. When these three criteria all approximated the critical values, the endothelium was regarded as in a predecompensation state that heralded impending endothelial decompensation. Therefore, these values may be regarded as a reference standard for diagnosing early stage endothelial decompensation. PMID- 2582947 TI - [Meibomian gland adenocarcinoma with regional lymph node metastasis]. AB - Meibomian gland carcinoma of the eyelid is a common neoplasm which clinically simulates a benign condition of chalazion. Although growing slowly, metastasis to regional lymph nodes is frequent, at a rate of 17-28% in this country. Eleven (11) cases of Meibomian gland carcinoma with regional lymph node metastasis are reported, and the therapeutic modalities have been tailored to suit the individual cases, including full-thickness local excision, orbital exenteration, radical cervical dissection, and superficial parotidectomy. PMID- 2582948 TI - [Clinical use of orbital implant in autogenous sclera]. AB - The authors embedded orbital implants wrapped up in autogenous sclera into 11 patients after enucleation, with sutures to fix the sclera to external ocular muscles. Tenon's capsule, and conjunctiva. The total volume of the implant was about 6 cm3 and the weight less than the eyeball. A shell was placed into the cul de-sac after the operation to be replaced by a prosthesis 6 weeks later. No extrusion or displacement of the implants occurred in follow-ups of 6 months to 2 years and the cosmetic effect was good. Tissue tolerance and ample motility could have resulted from the scleral wrapping and suture fixation to the muscles. PMID- 2582949 TI - [Electron microscopy of the angioarchitecture of the human iris and ciliary body]. AB - With the corrosion cast technique and electron microscopy, the major arterial circle of the iris, formed by the terminal branches of the medial and lateral long posterior ciliary arteries and of the anterior ciliary arteries, is shown not an anastomosed vascular ring but divided small branches of the arteries to supply the iris and ciliary body. The iris vessels demonstrate a radiate distribution of about 180-200 branches. The calibres of the iris arteries are homogeneous and measure about 50-120 microns. The branching portion of a precapillary arteriole begins with a constriction. The vessels of the ciliary processes account for more than half the volume of the ciliary body and have a rich capillary network of at least two layers. The draining veins are located on the surface and at the base of the ciliary body. There are 7-10 draining veins between two ciliary processes. PMID- 2582950 TI - [Genetic study of retinoblastoma]. AB - Eight patients with retinoblastoma were studied by high resolution chromosome R banding technique, and the EsD was quantitatively determined in red blood cells of the patients. Among these patients, two cases showed 13 q 14 deletion mosaicism, one showed a monosomy 13 q 14.1----q 14.2, and the rest had normal karyotype. The EsD activity was proportional to the number of copies of 13 q 14.1 region present. Our findings indicate that (1) the RB gene is located at 13 q 14.1, a region which is critical in the etiology of retinoblastoma, (2) 13q deletion is an important event in the development of retinoblastoma, and (3) EsD determination is an important diagnostic tool in the detection of 13 q deletion, useful for prenatal diagnosis and genetic counselling, permitting early institution of treatment upon early diagnosis. PMID- 2582951 TI - [Ultrastructural observations on the fetal corneal epithelium]. AB - The maturing changes in the central corneal epithelium of 18 fetuses were observed by transmission electron microscopy, revealing that the corneal epithelium comprised 5-6 layers of cells after the 8th month of gestation, when the basal cells were short columnar in shape with oval, regular nuclei, and the cytoplasmic organelles included mitochondria. Golgi complexes, rough endoplasmic reticulum, membrane coating granules, glycogen granules etc. In the middle layers were polygonal cells with flat nuclei and few cytoplasmic organelles. The free surfaces of the superficial flat cells were covered with microvilli of different heights and in random arrangement. The study confirmed that ultrastructurally the fetal corneal epithelium after the 8th month achieved the mature form of the adult cornea. PMID- 2582952 TI - [Functional dominance in the lacrimal canaliculi]. AB - Past reports ignored the functional relationship between the upper and lower lacrimal canaliculi. The authors measured the lacrimal function in 50 normal eyes of 27 subjects and found that the drainage was more rapid in the lower lacrimal canaliculi of 25 eyes and in the upper canaliculi of 22 eyes, while the drainage time was equal in 3 eyes. The drainage in 25 eyes with both the upper and lower canaliculi open was more rapid than with any one canaliculus occluded. The authors suggested that the function of the lacrimal canaliculi might be classified into three types: the dominating, the dominated and the balanced. There was no statistical difference (P greater than 0.05) between the numbers of dominating upper or lower canaliculi in this series. The function of the upper and lower canaliculi operated synergically and complete drainage was not accomplished by any one canaliculus alone. PMID- 2582953 TI - [Determination of the conjunctival goblet cell density in 43 normal subjects]. AB - The goblet cell density in the nasai inferior fornical conjunctiva was determined in 43 normal subjects (57 eyes). The mean number of goblets per 100 epithelial cells was found to be 10.17 +/- 2.81 in the young averaging 25 years and 5.25 +/- 3.38 in the aged averaging 62 years (P less than 0.01). The relation between the morphological features of the epithelial cells and the number of goblet cells was discussed. PMID- 2582955 TI - [An experimental study of the ocular hypotensive action of dopaminergic antagonists]. AB - The ocular hypotensive action of a group of dopaminergic antagonists was observed in the low intraocular pressure model of albino rabbits infused with 20% NaCl. It was found that haloperidol lowered IOP significantly in both eyes, though the drug was administered in one eye. Compared with timolol and pilocarpine, the strength in lowering IOP was in the order haloperidol greater than timolol greater than pilocarpine. Haloperidol did not affect the pupil. It may be a promising antiglaucoma agent. PMID- 2582954 TI - [Injurious effects on the rhesus monkey eye from dye laser iridotomy]. AB - 8 normal rhesus monkeys were performed dye laser iridotomy in one eye and iridectomy surgery in the other. Another 7 normal rhesus monkeys were performed dye laser iridotomy in one eye and ruby laser iridotomy in the other. The protein content and the number of white blood cells in the aqueous humor, the intraocular pressure, and the ultrastructural changes in the pars plicata of the ciliary body and iris were observed after the operation. It was demonstrated that the intercellular space of the endothelium of the blood vessels in the iris might, like the intercellular space of the non-pigment epithelium in the pars plicata of the ciliary body, be the site of the blood-aqueous barrier of the eye. It was also shown that among these three modalities, dye laser iridotomy was the best, which induced the least injury to the blood-aqueous barrier with the shortest time for recovery and the least inflammatory reactions in the anterior segment of the eye. PMID- 2582956 TI - [An epidemiologic survey of trachoma in Shunyi County, Beijing]. AB - The report presents the results of an epidemiologic survey of trachoma in Shunyi County, Beijing, conducted in 1985, revealing that trachoma was the major eye disease in Shunyi County with a prevalence of 38.68%, which obviously related with age. Most of the trachoma patients were mild cases; only 2.88% were of the severe type, while trachomatous complications occurred in 10.50% of the patients. The morbid characteristics of trachoma in rural areas and measures of treatment and prevention are discussed. PMID- 2582957 TI - Flow cytometry chamber with 4 pi light collection suitable for epifluorescence microscopes. AB - A compact, solid, spherico-ellipsoidal chamber (SEC), which has approaching 4 pi ("all around") light collection, has been developed for flow cytometry. This was mounted onto the stage of a standard fluorescence photomicroscope, and the camera was replaced by a photomultiplier. Both components can be added or removed in minutes. The increased light collection efficiency of the SEC (about 85%) compared with about 4% from standard chambers enabled a fluorescence microscope with a 50 W mercury vapour lamp to "double" as a flow cytometer. The system was tested with microbeads and cells stained for DNA with ethidium bromide, and results were comparable to those obtained with our laser-based instrument. PMID- 2582958 TI - A simple and rapid method for determining the linearity of a flow cytometer amplification system. AB - We describe a simple and rapid method for determining the linearity of a flow cytometer amplification system. The method is based on a fundamental characteristic of linear amplifiers: The difference between two amplified signals increases linearly with increasing amplifier gain. Two populations of beads or cells, differing slightly in fluorescence intensity, are analyzed by the flow cytometer at increasing photomultiplier tube high-voltage settings. The distribution of the populations' mean difference versus mean position is a straight line intersecting the origin for linear amplifiers. Although some types of nonlinearities cannot be detected with this technique, deviations from linearity indicate nonlinear components in the flow cytometer amplification system. The correlation coefficient is used to quantify degree of nonlinearity. We also describe a method for amplifier nonlinearity compensation. PMID- 2582959 TI - Statistical evaluation of cell kinetic data from DNA flow cytometry (FCM) by the EM algorithm. AB - Flow cytometric DNA measurements yield the amount of DNA for each of a large number of cells. A DNA histogram normally consists of a mixture of one or more constellations of G0/G1-, S-, G2/M-phase cells, together with internal standards, debris, background noise, and one or more populations of clumped cells. We have modelled typical DNA histograms as a mixed distribution with Gaussian densities for the G0/G1 and G2/M phases, an S-phase density, assumed to be uniform between the G0/G1 and G2/M peaks, observed with a Gaussian error, and with Gaussian densities for standards of chicken and trout red blood cells. The debris is modelled as a truncated exponential distribution, and we also have included a uniform background noise distribution over the whole observation interval. We have explored a new approach for maximum-likelihood analyses of complex DNA histograms by the application of the EM algorithm. This algorithm was used for four observed DNA histograms of varying complexity. Our results show that the algorithm works very well, and it converges to reasonable values for all parameters. In simulations from the estimated models, we have investigated bias, variance, and correlations of the estimates. PMID- 2582960 TI - Reference standards for flow cytometry and application in comparative studies of nuclear DNA content. AB - Nuclear DNA mass in cells from a reference species can be used to obtain high resolution estimates of DNA mass from a target species. In our study of DNA mass in cells from 45 selected species, representing each of the major vertebrate classes, we have obtained values of from 1.5 to 110.0 pg of DNA. Because values in or near this range would be expected in the study of nuclear DNA mass in vertebrates and other organisms, the species in this report can provide a useful catalogue of references for comparative studies of DNA. PMID- 2582961 TI - Different opinions on classification of DNA histograms produced from paraffin embedded tissue. AB - Flow cytometric DNA ploidy determination has been regarded as an objective prognostic parameter in several types of human cancer. To test whether DNA histograms are similarly interpreted, a series of flow cytometric DNA histograms was posted to six investigators working in the field for independent classification. The histograms were produced from paraffin-embedded adrenal adenomas or non-neoplastic tissue and had several different patterns. Only 44% of the histograms were similarly classified by all investigators, and 85% by five of the six participants, when DNA ploidy was evaluated. Different criteria for tetraploidy existed, and also some uncertainty in classifying peridiploid and small aneuploid peaks. It is concluded that lack of consensus on histogram classification may result in widely varying percentages of DNA aneuploid tumors found even if the data are similar. Until general agreement is reached on the definition of DNA aneuploidy and its subclasses, classification of DNA histograms is variable and subjective. PMID- 2582963 TI - Flow cytometric evaluation of DNA stainability with propidium iodide after histone H1 extraction. AB - A flow cytometric evaluation of the effect of the histone H1 extraction on DNA stainability with propidium iodide was performed on isolated HeLa nuclei. Selective removal of the lysine-rich protein was attained by using two established techniques involving treatment with 0.7 M NaCl or low pH. DNA stainability was monitored at different dye/DNA-P ratios, varying from low to high saturating concentrations. Depletion of the histone H1from nuclei results in the transition from low to high affinity of a portion of binding sites, as shown by 1) the increase in fluorescence intensity after staining with the dye at low saturating concentrations and 2) the higher value of the fluorescence intensity ratio (FI5/FI50) exhibited by H1-depleted nuclei stained with a low (5 micrograms/ml) vs. a high (50 micrograms/ml) concentration, as compared with control samples. PMID- 2582962 TI - Thermal denaturation of DNA for immunochemical staining of incorporated bromodeoxyuridine (BrdUrd): critical factors that affect the amount of fluorescence and the shape of BrdUrd/DNA histogram. AB - Significant inter- and intraexperimental variations of the relative antibromodeoxyuridine fluorescence were found during measurement of DNA synthesis rates using flow cytometric analysis of 5-bromodeoxyuridine (BrdUrd)-labeled cells with an anti-BrdUrd antibody. Fluctuations in other endpoints associated with levels of denaturation (integrity of DNA and cell size) were also observed to vary widely among samples that were otherwise thought to have been treated identically. Therefore, the denaturation step has been carefully re-examined, and several critical factors were identified that influence the denaturation and subsequent binding of the anti-BrdUrd to the labeled DNA. These factors include cell density, volume of water, and pH of the sample during heating. Appropriate adjustments are now included in the protocol, resulting in more consistent anti Brd-Urd measurements in the face of routine (and sometimes necessary) experimental variations. PMID- 2582964 TI - Measurement variability in DNA flow cytometry of replicate samples. AB - A Bladder Cancer Flow Cytometry Network study has been carried out aimed at identification of the sources of inter- and intralaboratory variability. Replicate "cocktail" samples containing a mixture of peripheral blood lymphocytes and an aneuploid cell line and samples of peripheral blood lymphocytes serving as a DNA reference standard were distributed to five network laboratories. The samples were stained for DNA using propidium iodide, with each laboratory using its own staining protocol. Sets of these samples were analyzed by flow cytometry to obtain cellular DNA distributions. DNA index and hyperdiploid fraction were calculated for each histogram using an automated technique. Results were evaluated by analysis of variance to identify sources of variability. Three important sources of variation were found that affect flow cytometry in general and- the transportability of flow cytometry results to routine clinical use in particular. The significant variation among laboratories that is constant across time most probably represents stable differences in instrumentation, instrument set-up, and laboratory techniques. This variation can be compensated for, if it is known and stable, to develop transportable classification criteria. The second type of variation, termed the interaction component, represents differences among laboratories that are not constant across time. Sources of this variation include inconsistency in sample preparation, staining, and analysis. The elimination of this type of variation is required for meaningful comparison of data within and among laboratories and the creation of interlaboratory data-bases. The third type of variation represents pure measurement variability and affects the sensitivity of the technique. PMID- 2582966 TI - Flow cytometric analysis of protein thiol groups in relation to the cell cycle and the intracellular content of glutathione in rat hepatocytes. AB - The relationship between protein thiols (PSH) and cell proliferation was examined in ethanol-fixed rat hepatocytes. A new protocol was developed for simultaneous measurement of protein thiol vs. DNA content by flow cytometry. The fluorescent dye o-phthalaldehyde (OPT) was used for flow cytometric measurements of protein thiol groups. The influence of nonprotein thiols was examined by monitoring the cell cycle of cells in which the glutathione content (GSH) was modified by treatment with buthionine sulphoximine (BSO). Three rat liver cell lines (IAR 20, IAR 6.1, IAR 6.1RT7) were used: these cell lines possess different growth characteristics and degrees of tumorigenicity, which made it possible to analyse changes in PSH during normal and deranged cell proliferation. The effects on the cell cycle of the changes in PSH due to the depletion of GSH were measured by 5 bromo-2'-deoxyuridine (BrdUrd) incorporation and flow cytometry. The data obtained can be summarised as follows: a) OPT fluorescence increases with increasing DNA content in all rat liver cell lines examined; b) the greatest variation in PSH content occurs in G1. There is a smaller variation in G2 + M, and PSH levels are relatively invariant throughout S-phase; c) a higher content of PSH is found in the tumorigenic cell lines; d) the amount and distribution of PSH is not affected by BSO treatment; e) kinetic studies indicate that BSO treatment has no effect on the ability of the IAR rat liver cell lines to progress through the cycle. PMID- 2582965 TI - Detection of bladder carcinoma in females by flow cytometry and cytology. AB - The sensitivity of bladder wash flow cytometry (BWFCM), voided urinary cytology (VUC), and cytology of catheterized urine obtained at the time of cystoscopy (CUC) were reviewed on all women evaluated for bladder cancer at Memorial Sloan Kettering Cancer Center between June 1985 and December 1986. This comprised sixty four episodes of pathologically proven bladder cancer in 48 women. Considering positive and suspicious results jointly the sensitivities of BWFCM, CUC and 3 VUC were 75%, 64% and 56%, respectively. If only positive results were considered (i.e., suspicious results considered as negative), the sensitivities of BWFCM, CUC and 3 VUC were 64%, 31% and 32%, respectively. The sensitivities of these tests are less than for a predominantly male population, presumably related to the presence of squamous epithelium and greater frequency of pyuria. However, bladder wash flow cytometry and conventional cytology are still a very valuable addition to cystoscopic examination, and the combination of BWFCM with conventional cytology is more sensitive than either procedure alone. PMID- 2582967 TI - Dual-parameter flow cytometric analysis of an early lymphocyte activation antigen (CK226) and DNA content. AB - This study provides a direct correlation, via dual-parameter flow cytometric analysis (simultaneous assessment of surface immunofluorescence and DNA content), between activated T-cell entry into the S/G2/M phases of the cell cycle and the kinetics of expression of a novel T-cell activation antigen, termed CK226. This molecule was identified by the specific monoclonal antibody on the leukaemic T cell line CEM/K, and it was expressed by 8-30% of resting peripheral blood lymphocytes and the majority of monocytes and granulocytes. A large fraction of activated lymphocytes acquired the CK226 antigen before DNA synthesis. Moreover, this molecule was expressed on virtually all G0/G1 and S/G2/M phase cells by day 2 after phytohaemagglutinin (PHA) activation and at day 6 after stimulation in a mixed lymphocyte culture. The time course of expression of other known activation antigens, such as Tac and transferrin receptor, was comparable to that of CK226. Based on the relationships between CK226 expression on cycling cells and the stimulatory effects of the specific monoclonal antibody, we conclude that CK226 should be considered an early activation antigen, which defines a new pathway of T-cell activation. PMID- 2582968 TI - Separation of hepatocytes of different acinar zones by flow cytometry. AB - Hepatocytes in the proximal (zone 1) and distal (zone 3) regions of the liver acinus are selectively stained by perfusion of the isolated rat liver with 0.2-20 microM acridine orange (AO). After 10-60 min of anterograde perfusion, AO fluorescence is visible in zone 1 cells, whereas retrograde perfusion stains cells of zone 3. In this paper, we describe a technique to isolate a mixed population of fluorescent and nonfluorescent hepatocytes (cells from all acinar zones, which do not loose the zone specific AO labeling) and to separate these cells according to their zonal origin by fluorescence activated cell sorting. The zonal populations obtained were either fluorescent or nonfluorescent (purity greater than 95%). Separated cell fractions differed in their enzyme content (5' nucleotidase, succinate-dehydrogenase, beta-glucuronidase). An unidentified AO metabolite, which is not found in bile after retrograde perfusion (not formed in zone 3 cells), is also absent after retrograde perfusion in sorted fluorescent cells (zone 3 cells), indicating zonal purity of sorted cells. PMID- 2582969 TI - Separation of pigmented and albino melanocytes and the concomitant evaluation of endogenous peroxide content using flow cytometry. AB - Flow cytometry (FCM) has been used extensively to analyze various biological properties of the cell. In this report, we describe a method by which FCM was used to determine the light scattering profile of a mixed population of pigmented and non-pigmented melanocytes, plus its subsequent use for the sorting and separation of the two cell types. In addition, the relative peroxide content in pigmented and non-pigmented melanocytes was compared by flow cytometry. Cultured avian melanocytes from a pigmented control and from three genetically distinct albino sources were studied. FCM analysis of forward versus side light scatter within a mixed suspension of pigmented and amelanotic melanocytes distinguished two overlapping populations of cells. Sorting of these two populations demonstrated that the population exhibiting much side and minimal forward light scatter was primarily pigmented melanocytes, while conversely the population exhibiting less side and more forward scatter was principally non-pigmented cells. These two melanocyte types also demonstrated differences in levels of endogenous peroxides. The intracellular content of peroxide in the two subpopulations of cells was measured utilizing the nonfluorescent compound, 2',7' dichlorofluorescein diacetate (DCFH-DA), which within the cell is oxidized by intracellular peroxides to a fluorescent dichlorofluorescein (DCF). Non-pigmented albino melanocytes had the highest quantity of endogenous peroxides, while heavily pigmented cells had considerably less peroxide-related fluorescence. The amount of this DCF fluorescence could be enhanced by increasing concentrations of DCF used in the assay. These flow cytometric methods are useful for isolating and culturing subpopulations of melanocytes expressing various pigment levels and to investigate the relationship between melanin and its precursors with hydrogen and lipid peroxides in melanocytes. PMID- 2582971 TI - Sample station modification providing on-line reagent addition and reduced sample transit time for flow cytometers. AB - A flow cytometer was equipped with a modified sample station to facilitate on line addition of mediators to the sample and reduce the time of delivery of the sample to the interrogation point. The ready availability of materials and straightforward nature of this design make modifications simple and facilitate measurements of cellular activation. Parameters such as pH, membrane fluidity, and calcium mobilization are easily measured in this system, because detection can be made less than 4 s after addition of mediator with no interruption of sample flow. The sample station modification is described in detail along with methods for mixing and temperature control. PMID- 2582970 TI - Flow cytometric analysis of the kinetic effects of cisplatin on lung cancer cells. AB - The effects of cisplatin on the cell cycle and DNA synthesis of human lung adenocarcinoma cell line PC-9 were examined by flow cytometry. The cellular DNA content and the bromodeoxyuridine (BrdUrd) incorporation rate were measured simultaneously using a monoclonal anti-BrdUrd antibody. Following exposure to cisplatin (1.0 micrograms/ml) for 1 and 24 hr, the bivariate DNA/BrdUrd distributions revealed a delayed S-phase transit and an accumulation of cells in the G2M phase. The BrdUrd-linked green fluorescence intensity continued to decrease with the lapse of time. However, early- and mid-S-phase cells soon recovered DNA synthesis activity, and the former showed higher activity than the control cells. These findings suggested the vigorous DNA synthesis of cells in early S phase. However, for quantitative analysis of chemotherapeutic effects, some problems remained to be resolved regarding the condition for DNA denaturation and its alteration by the agents. PMID- 2582973 TI - Cytokinetic analysis of lung cancer by bromodeoxyuridine labeling of cytology specimens. AB - Recent flow cytometric (FCM) studies have indicated the prognostic value of S phase cells (SPF) in lung cancer. More refined cytokinetic analysis can be obtained by dual-parameter FCM, labeling S-phase cells with 5-bromodeoxyuridine (BrdUrd), which can be detected using a monoclonal antibody (MoAb) to BrdUrd. Tumor cells obtained through bronchoscopic brush were incubated for 1 hr in RPMI 1640 medium with 10% fetal calf serum and 10 microM BrdUrd. After fixation in ethanol, pepsin treatment, and DNA denaturation, the nuclei were stained with anti-BrdUrd MoAb and propidium iodide. From 14 of 20 patients, sufficient material was obtained (three adenocarcinoma and seven squamous cell, one giant cell, and three small cell carcinoma). The measured SPF ranged from 5.2% to 26%. The labeling index (LI), calculated as the ratio of the number of BrdUrd-labeled cells to the total number of aneuploid cells, or diploid cells in the case of a diploid tumor, ranged from 1.2% to 16.7%; LI and SPF correlated significantly (r = 0.69). In this study, we have demonstrated the feasibility of determining the actively DNA-synthesizing cells on brush material from lung cancer cells. In addition, some extra information can be obtained about the SPF population, including the fraction of unlabeled SPF, which could be of prognostic significance. PMID- 2582974 TI - Modified Box-Cox transform for modulating the dynamic range of flow cytometry data. AB - We describe an algorithm, Vout = Integer ([2(12)-1/2(12 lambda)-1] V lambda in-1) + 1; lambda greater than 0 based upon Box-Cox transformations as an alternative to nonlinear electronic amplifiers to expand or compress high- or low-amplitude flow cytometer-derived signals. If the indexing parameter lambda less than 1, input channels in the high-amplitude input range are compressed in the output range as occurs when an electronic logarithmic amplifier is used. However, if lambda greater than 1, input channels in the low-amplitude input range are compressed in the output range as occurs when an electronic power amplifier is used. Our modified Box-Cox transform can be implemented either during data collection or off-line for the transformation of previously collected raw data. The transform is the equivalent of an infinite class of nonlinear amplifiers. As the transform is implemented in software, it does not suffer from many of the disadvantages of nonlinear electronic amplifiers. PMID- 2582972 TI - Use of xantham gum to suspend large particles during flow cytometric analysis and sorting. AB - In this report we describe the use of xantham gum as a biologically inert material for increasing the viscosity of a suspension of cells or particles during flow cytometric analysis and sorting. A 0.1% concentration of xantham gum in culture medium or saline will increase the viscosity approximately 9-fold. For suspensions of multicellular spheroids 100-400 microns in diameter the measured sedimentation velocity was approximately 9 times slower than that in medium alone. Thus, spheroids of 100 microns diameter remain in suspension in 0.1% xantham gum for 66 min, compared to 7.5 min in culture medium. This allows extended periods of sorting without stirring or agitating the sample suspension. The xantham gum solution is noncytotoxic for periods up to 8 h as measured by clonogenicity assay. Xantham gum has the added advantage that the viscosity is significantly reduced when the solution is subjected to shear stress, such as during flow. This technique should be applicable to extended sorting of suspensions of spheroids, plant cells, and other large particles, as well as for analyzing and sorting single cells for extended periods. PMID- 2582975 TI - INCA: software for consort 30 analysis of flow cytometric calcium determinations. AB - The INCA program converts Consort 30-generated fluorescence list mode data collected from Indo-1-stained cells to absolute intracellular calcium concentrations (nM Ca2+i). The calcium data are plotted vs. time, allowing the user to analyze the fractions of cells responding to a given stimulus. Converted files can be restored to disk after replacing FL1 and FL2 with time and calcium, respectively, for future analysis. PMID- 2582976 TI - Noncardiac chest pain. The crumbling of the sphinx. PMID- 2582977 TI - Spontaneous noncardiac chest pain: value of ambulatory esophageal pH and motility monitoring. AB - We performed esophageal investigations in 20 patients suffering from noncardiac chest pain in order to assess the diagnostic value of short- versus long-term manometric and pH studies. Patients had baseline esophageal manometry with two provocative tests: a Bernstein test and an intravenous injection of edrophonium. On a separate occasion they had a 24-hr ambulatory esophageal pH and motility recording. The Bernstein test provoked chest pain in two patients, while edrophonium injection did not elicit pain in any of the patients. The ambulatory pH study helped to establish the esophagus as the likely source of pain in one patient, and the ambulatory motility one in another. In our experience, ambulatory pH and motility recordings have a low diagnostic yield in the evaluation of patients with noncardiac chest pain. PMID- 2582978 TI - Modulation of esophageal peristalsis by alterations of body position. Effect of bolus viscosity. AB - Previous studies have demonstrated that nonviscous liquids traverse the esophagus more rapidly with the subject in the upright rather than the supine position. Conversely, similar studies have shown that viscous liquids traverse the esophagus at similar rates for both upright and supine positions. Our purpose was to define the motor correlates of these differing responses. Six normal volunteers were studied with an infused catheter system incorporating a Dent sleeve for monitoring lower esophageal sphincter pressure. The subjects were given a series of swallows of a water and a viscous (52 centipoise) bolus in both the supine and upright positions. In the upright position, the water bolus caused an increased velocity of propagation in the proximal esophageal segment that was associated with a shortening of lower esophageal sphincter relaxation time and reductions in amplitude and duration of contraction. No significant changes in the peristaltic wave were noted with the viscous bolus during alterations of body position. We conclude that the more rapid transit of a nonviscous water bolus through the esophagus in the upright position is reflected in specific alterations of esophageal peristaltic parameters. The possible mechanisms for these differing responses are discussed. PMID- 2582979 TI - Motility changes in opossum esophagus from experimental esophagitis. AB - We assessed how acute inflammation affects the contractile activity of the esophageal body. Two models of esophagitis were used: nine opossums had an esophageal perfusion of 100 meq hydrochloric acid for 2 hr and were studied at 24 hr. Ten had the perfusion for 4 h and their esophagitis were studied in vitro after 72 hr. Comparisons were made in all instances to animals who had esophageal saline perfusion for identical periods. All acid-perfused animals developed gross and histologic evidence of mucosal inflammation; in three animals, inflammatory changes extended into the submucosa and the muscularis propria. Manometric recordings in the acid-perfused animals revealed esophageal shortening, frequent failure of primary peristalsis and frequent occurrence of spontaneous contractions. Recordings of isometric tension of muscle in vitro revealed spontaneous contractions in strips from the mucosa and from the circular and from the longitudinal muscle. The amplitude of contractions in response to electrical stimulation was decreased, but the duration of contractions was increased largely because of a prolonged recovery phase. These changes in mechanical response occurred with stimulus parameters directed at both the muscle and the intrinsic nerves. We conclude that esophageal inflammation can lead to an increased irritability and decreased stimulus response of the smooth muscle of the esophagus even where it is not directly involved in an inflammatory response. These changes correspond to the functional abnormalities of the esophagus seen in patients with reflux esophagitis. PMID- 2582980 TI - Campylobacter pylori is not associated with gastroparesis. AB - There is a high incidence of Campylobacter pylori in the gastric mucosa of patients with duodenal ulcer, gastric ulcer, and nonulcer dyspepsia. Factors that lead to development of this infection are unknown. We hypothesized that delayed solid-phase gastric emptying, a condition characterized by antral stasis, might predispose to Campylobacter pylori infection. We prospectively studied 51 patients with symptoms of gastroparesis using a solid-phase gastric emptying study and upper endoscopy. Patients were excluded if they had predominant symptoms of epigastric pain or an abnormal endoscopy. Three biopsies were obtained from the antrum and stained with H&E. When any inflammation was present, a Warthin-Starry stain was also performed. These were blindly examined for chronic inflammation, activity, and presence of Campylobacter pylori. Campylobacter pylori was not more common in patients with gastroparesis, documented by delayed gastric emptying, than in patients with a normal emptying study. On the contrary, there was a significantly lower incidence of Campylobacter pylori in those with delayed emptying compared to those with normal emptying (5% vs 31%, P less than 0.05). Gastritis activity correlated closely with Campylobacter presence. Inactive chronic gastritis with Campylobacter was equally common in those with delayed or normal gastric emptying. Diabetics were no more likely to harbor Campylobacter pylori than nondiabetics (16% vs 25%). The 5% incidence of Campylobacter in the gastroparesis group is less than, but approaches, that previously reported in asymptomatic controls. The 31% incidence of Campylobacter in the group with symptoms of gastroparesis but normal gastric emptying approaches that reported for nonulcer dyspepsia. Our data suggest that gastroparesis does not predispose to Campylobacter pylori infection or histologic chronic gastritis. PMID- 2582981 TI - Exogenous prostaglandin protects against acid-induced deep mucosal injury by stimulating alkaline secretion in rat duodenum. AB - In the anesthetized rat, exogenous acid (0.1-0.3 N HCl) perfused through the duodenum produced a dose-related increase in the severity of duodenal villous injury. Increasing the duration of perfusion of the 0.1 N HCl also increased the severity of the injury. The increase in the severity of the lesion score was due to an increase in the percentage of villi with damage extending to the lower half of the villus. 16,16-Dimethyl prostaglandin E2 (dm PGE2, 5 micrograms/kg) administered subcutaneously significantly increased duodenal mucosal alkaline secretion and significantly reduced the duodenal villous injury produced by 0.1 N HCl. The reduction in the severity of the lesion score was due to a decrease in the percentage of villi with the deeper type of damage. These data indicate: (1) perfusion of the rat duodenum with 0.1 N HCl at 0.1 ml/min for 30 min provides a valid model for assessing deep duodenal villous injury, (2) exogenous prostaglandin enhances the resistance of the duodenal mucosa against acid induced deep villous injury, and (3) the enhanced resistance may be mediated at least in part by stimulation of duodenal alkaline secretion. The results support the hypothesis that stimulated duodenal alkaline secretion may play a role in defense of the duodenal mucosa against acid-induced deep villous injury. PMID- 2582982 TI - Morphologic changes in gastric mucosa of aging rats. AB - We examined histologic and ultrastructural changes in the gastric mucosa of aging rats. Standardized gastric specimens from Sprague-Dawley rats 3 months of age (young) and 24 months of age (old) were evaluated by qualitative and quantitative histology and transmission electron microscopy. Old rats had the following histologic changes: (1) partial atrophy of the gastric glands and their replacement with hyalinlike connective tissue; (2) cystic dilatation of the gastric glands at the bases with occasional squamous cell metaplasia; and (3) extensive perivascular depositions of PAS-positive material, negative for amyloid. The total mucosal thickness was 484 +/- 100 microns in young rats vs 1122 +/- 240 microns in old rats (P less than 0.01). Electron microscopy demonstrated degenerative changes in parietal and chief cells, hyperplasia of surface and foveolar mucous cells, and prominent accumulation of disorganized collagen fibrils in perivascular connective tissue. This study indicates that the gastric mucosa of aging rats that have not been exposed to damaging agents does show definite histologic and ultrastructural changes. PMID- 2582983 TI - Differential effects of acute mental stress on interdigestive secretion of gastric acid, pancreatic enzymes, and gastroduodenal motility. AB - To study the effects of acute mental stress on gastric and pancreatic secretion, 12 healthy fasting volunteers swallowed two multilumen tubes, which allowed continuous aspiration of gastric and duodenal juices and measurement of motility of the stomach and the duodenum. In each study at least three duodenal phase III complexes of the migrating motor complex were recorded. In randomized order after the first or second duodenal phase III, mental stress was induced for 60 min by means of solving anagrams and doing mental arithmetic. Mental stress significantly increased the duration of the migrating motor complex by 60% (137.9 +/- 16.3 vs 86.1 +/- 13.0). Gastric flow rate and gastric acid output were not significantly altered. Duodenal flow rate was not changed during the stress period but significantly decreased by more than 52% in the following 30-min resting period. Duodenal concentration and output of chymotrypsin were significantly increased during the second 30-min period of acute mental stress; chymotrypsin output was significantly reduced in the poststress period. We conclude that acute mental stress has different effects on the stomach, the pancreas, and the upper gastrointestinal motility. The mechanisms by which the central nervous activity induced by mental stress affects the motility and secretion of the upper gastrointestinal tract remain to be elucidated. PMID- 2582984 TI - Bombesin: an activator of specific Aeromonas antibody secretion in rat intestine. AB - The effect of bombesin (BBS) in modulating the secretion of specific Aeromonas antibodies in rat intestine was determined. Rats were immunized with the culture supernatant of Aeromonas hydrophila, isolate SSU. This culture supernatant contained a number of toxins that may be considered virulence factors. After 24 days of immunization, rats were anesthetized and a 10-cm intestinal segment was perfused with phosphate-buffered saline. The effluents were collected for measurement of IgA and IgG by the enzyme-linked immunosorbent assay. When compared with the effect of intravenous administration of normal saline in the control group, intravenous injection of BBS (20 micrograms/kg) in the experimental group caused a significant increase in rat intestinal IgA and IgG in perfusates. The stimulatory effects of BBS on the presence of IgA and IgG were depressed partially by proglumide, a receptor antagonist of cholecystokinin (CCK) and gastrin. Treatment with pentagastrin (250 micrograms/kg) accelerated intestinal secretion of IgA, but failed to stimulate intestinal IgG secretion. In addition, intravenous injection of CCK-8 (120 ng/kg) evoked the intestinal secretion of either IgA or IgG. These findings demonstrated that BBS, gastrin, and CCK can stimulate antibody secretion in rat intestine and the stimulatory effect of BBS may be mediated partially via release of CCK and gastrin. These results suggest that neuropeptides such as BBS and gastrointestinal hormones, eg, CCK and gastrin, may participate in the regulation of intestinal secretion of IgA and IgG antibodies, respectively, in rats. PMID- 2582985 TI - Period and generation effects on mortality from idiopathic inflammatory bowel disease. AB - To test the hypothesis that environmental factors play a role in idiopathic inflammatory bowel disease (IBD), age, period, and generation (cohort) effects on IBD mortality in the United Kingdom and the United States were examined. The crude death rate of ulcerative colitis has declined since 1930. Plotted versus the year of birth, its age-specific death rates showed an initial rise in successive generations born between 1850 and 1900, followed by a fall in all later generations. The crude death rate of Crohn's disease increased from 1950 to 1974 and then declined. When the age-specific death rates for Crohn's disease and ulcerative colitis were superimposed, the mortality from Crohn's disease in each age group or sex began to decline at a different time, but always upon reaching the level of mortality from ulcerative colitis. It appears as if the gradual disappearance of an ulcerative colitis-associated factor in a birth-cohort fashion prevented a further rise in mortality from Crohn's disease after 1974. PMID- 2582986 TI - Lymphocytic (microscopic) colitis. Clinicopathologic study of 18 patients and comparison to collagenous colitis. AB - Lymphocytic colitis, formerly called microscopic colitis, is a clinicopathologic syndrome with chronic watery diarrhea and diffuse mucosal inflammatory changes with prominent intraepithelial lymphocytes. The 18 lymphocytic colitis patients studied presented with chronic watery diarrhea at a mean age of 53.8 +/- 17 years (+/- 1 SD). Roentgenographic, endoscopic, and culture data were not diagnostic. In patients tested, there was a high prevalence of arthritis (82%) and autoantibodies (50%) but no increase in frequency of histocompatibility antigens associated with well-defined autoimmune disease (DR3, B8). Lymphocytic colitis patients were compared to 21 patients with collagenous colitis. Similarities included age, symptomatology, and nondiagnostic radiographic and endoscopic studies. However, the sex distribution was statistically different, with an equal male-to-female ratio in lymphocytic colitis and female predominance (80%) in collagenous colitis. Other differences included dissimilar histocompatibility phenotypes and collagen band on biopsies of collagenous but not lymphocytic colitis. These findings suggest that lymphocytic and collagenous colitis may be related yet distinct disorders. PMID- 2582987 TI - Does milk have a cataractogenic effect? Weighing of clinical evidence. AB - We undertook a prospective study to test Simoons' hypothesis that in certain susceptible races milk exerts a cataractogenic effect. Overall milk intake in low lactase deficiency areas did not correlate with cataract occurrence. Subgrouping of cataract patients revealed that greater milk intake did show positive correlation with cortical cataracts. Cortical cataracts were also markedly more common in females. Analysis of data from three different regions showed greater milk intake in cortical cataract patients only. Our data indicate the importance of specifying cataract type in cataract studies and highlight the problem this approach brings forth. We noted no different trends in subjects from northwest and southeast India, although the number of subjects from the southeast was considerably less. Patients with early cortical cataracts may be advised to restrict milk intake. PMID- 2582989 TI - Ultrastructure of another spiral organism associated with human gastritis. AB - Campylobacter pylori may not be the only organism that causes active chronic gastritis in man. We report two cases of gastric infection with a spiral organism distinct from C. pylori. The first patient is a 36-year-old female who presented with epigastric pain and abdominal colic present since childhood and who had 14 cats. Endoscopy was normal. The second patient kept two dogs. Histology of gastric mucosal biopsy specimens in both patients revealed active chronic gastritis, most severe in body mucosa. Giemsa stain revealed bacteria with four to eight spirals, 0.5 micron in diameter and 3-7 micron in length. The organisms had multiple sheathed flagella at the pole and smooth cell walls without axial filaments. The organisms resembled the gastric spirillum that has been seen in cats, dogs, and nonhuman primates. After antibacterial therapy with bismuth subsalicylate, amoxicillin, and metronidazole, the organisms disappeared in both patients and the gastritis healed. Unlike C. pylori, this new spirillum prefers to colonize gastric mucosa containing parietal cells. Whereas this type of organism is a common commensal in other mammals, it appears to be associated with and a possible cause of gastritis in humans. PMID- 2582988 TI - Effect of bradykinin on feline gallbladder water transport and prostanoid formation. AB - Continuing evaluation of the pathophysiology of gallbladder disease has demonstrated significant relationships between gallbladder mucosal fluid transport, gallbladder inflammation, and prostanoid formation. Inflamed gallbladder mucosa secretes, rather than absorbs, fluid, a process associated with prostaglandin formation. Bradykinin has been previously implicated in the pathogenesis of cholecystitis and, in the intestine, bradykinin stimulates mucosal fluid secretion by a prostaglandin-mediated mechanism. Bradykinin was infused into the gallbladder lumen and administered intraarterially into the hepatic artery of perfused cat gallbladders. Both methods of bradykinin administration reversed the mucosal absorption present during control experiments as measured by concentration changes in a nonabsorbable marker. Perfusate and gallbladder tissue prostaglandin E concentrations were significantly increased by bradykinin when compared to control values. Concentrations of 6-keto PGF1 alpha in perfusate solutions and in gallbladder tissue were significantly increased, suggesting bradykinin increased prostacyclin formation. Bradykinin administration significantly increased inflammation, as evaluated by a histologic scoring system. Indomethacin was administered intravenously along with luminal perfusion of the gallbladder with bradykinin. Indomethacin significantly decreased gallbladder fluid secretion and prostanoid formation, but not histologic inflammation, when compared to values produced by bradykinin alone. An increase in systemic vascular and bile kinin concentrations produces gallbladder mucosal water secretion, a process which may be mediated by prostanoids. Histologic inflammation produced by bradykinin was not prevented by indomethacin. PMID- 2582990 TI - Quantitative distribution of radiolabeled 5-aminosalicylic acid enemas in patients with left-sided ulcerative colitis. AB - Rectally administered suspensions of 5-aminosalicylic acid (5-ASA) are topically effective in treating left-sided ulcerative colitis. The extent to which the contents of these enemas are distributed to inflamed mucosal linings has not previously been determined. This study was undertaken to validate a technique for labeling 5-ASA with 99mTc and to quantitate the distribution of [99mTc]5-ASA in eight patients with left-sided ulcerative colitis. Eight patients underwent three colonic scintigraphic exams within five days, receiving a 60-ml radiolabeled 5 ASA enema into the unprepared rectum for each study, with sequential anterior abdominal images obtained for 4 hr. Activity within the rectum, sigmoid, descending, transverse, and ascending colon was quantitated. Over 50% of the labeled enema had advanced beyond the rectum in five of eight patients and in six of eight patients by 30 min and 60 min, respectively. The distribution of [99mTc]5-ASA was quantitatively reproducible when repeated in the same patient on different days, despite apparent visual differences. By 2 hr, the amount of the enema present within the rectum decreased significantly (P less than 0.05) compared to the initial distribution. The amount of enema present within the descending colon was increased significantly at 0.5 hr (P less than 0.05) and at 2 hr (P less than 0.01). There were no significant changes in the distribution from initial values for the sigmoid, transverse, or ascending colon at any time. In each of these cases the spread of the enema to or beyond the extent of disease was documented. In patients with left-sided ulcerative colitis, small volume [99mTc]5-ASA enemas reliably reach the area of inflammation. PMID- 2582991 TI - Fecal anions and lactate in severe ulcerative colitis. PMID- 2582992 TI - Campylobacter pylori in esophagus. PMID- 2582994 TI - Posterior chamber intraocular lens implantation in patients with retinitis pigmentosa. AB - 20 eyes of 12 Retinitis Pigmentosa patients underwent extracapsular cataract extraction followed by I.O.L. implantation. No unusual intra or post operative complications were encountered. All pseudophakic eyes showed improvement in visual acuity whereas the V.F. remained unaltered. Subjectively all 12 patients reported a benefit from surgery despite the Visual Field impairment. PMID- 2582993 TI - Reversible changes of visual acuity and pattern-electroretinograms after blue green argon laser photocoagulation of diabetic patients. AB - Visual acuity, color vision, pattern-visual-evoked-potentials (P-VEPs) and pattern-electroretinograms (P-ERGs) were measured in 13 diabetic subjects before, and 24 hours and 5 weeks after blue-green argon laser treatment. As control, the same examinations were performed in 7 normal subjects and 7 diabetic patients before and after slit lamp examination with the Goldman three mirror contact lens. Visual acuity and P-ERG amplitudes were significantly reduced one day after the laser treatment, while 5 weeks after the laser coagulation, visual acuity and P-ERG amplitudes recovered to pretreatment values. The control group showed no significant changes after slit lamp examination. Since fluorescein angiography revealed no macular changes after laser treatment, the possibility of a reversible functional light damage after blue-green argon laser coagulation (ALC) is discussed. PMID- 2582996 TI - Further evidence for the role of proprioception in space perception. AB - In this paper results are presented of errors in spatial localization found after encircling procedures for retinal detachment both in the operated and in the normal eye. Also changes in spatial localization were found in strabismus patients in which a stretch on the operated muscle was exerted after an adjustable recession. In both groups of patients a manipulation of the eye muscle was performed without inducing an eye muscle imbalance in the retinal detachment patients and without modifying the eye position in the strabismus patients in which a stretch was exerted. These data provide further evidence in favour of the role of proprioceptive information in space perception. PMID- 2582995 TI - Intraocular pressure responses to systemic autonomic stimulation in diabetes mellitus. AB - The acute changes in intraocular pressure during sustained handgrip contraction (2.5 minutes duration) and the Valsalva manoeuvre (15 seconds duration), both standard tests of autonomic nerve function were studied in 14 diabetic patients and 14 similar aged control subjects. During sustained handgrip contraction, diastolic blood pressure increased by 16.35 +/- 1.87 mmHg in the diabetic patients and 21.36 +/- 0.66 mmHg for the control group. Mean intraocular pressure decreased by 0.71 +/- 0.43 mmHg in the diabetics, p less than 0.05 and 0.64 +/- 0.27 mmHg, p less than 0.01) in the control group. There was no correlation between the blood pressure and the intraocular pressure responses in either group. On release of handgrip contraction, mean recovery intraocular pressure over 5 minutes was significantly lower than mean baseline values for the two groups; control: baseline 14.78 +/- 0.49 to 14.14 +/- 0.67, p less than 0.001 and diabetic: 14.57 +/- 0.65 to 13.86 +/- 0.72, p less than 0.001. During the Valsalva manoeuvre, there was a significant rise in intraocular pressure in the control (+7.85 +/- 0.75 mmHg, p less than 0.001) and the diabetic group (+7.93 +/ 1.18 mmHg, p less than 0.001). 5 minutes after release of intrathoracic pressure, mean recovery intraocular pressure remained significantly below baseline values for the two groups. The Valsalva ratios were in the normal range for the control group (1.21 to 2.2) while 2 diabetics had abnormal ratios. PMID- 2582997 TI - Difficulties in the definition of 'stereoscotoma' using temporal detection of thresholds of dynamic random dot stereograms. AB - Temporal detection thresholds are reported from two subjects to dynamic random dot stereograms (DRDSs) of both crossed and uncrossed disparity. The stimuli were 1 degree square, of 0.25 degrees disparity and were presented at 81 positions in a 9 degree square central region. In both subjects crossed disparity stimuli were detected at shorter durations. One subject displayed particularly acute stereoscopic vision and presented a pattern of temporal thresholds increasing gradually with eccentricity. The other subject displayed evidence, particularly in response to uncrossed stimuli, of a 'stereo-scotoma' which was not evident in monocular testing or ophthalmologic examination. Criteria used to define 'stereo scotoma' are discussed. It was concluded that, although left-right field differences may be found with a large subject sample, individual factors may be more important in the distribution of stereo sensitivity throughout the portion of visual field tested. PMID- 2582998 TI - Main posterior watershed zone of the choroid. Variations of its position in normal subjects. AB - The main posterior watershed zone of the choroid is located between the nasal edge of the optic disc and the fovea and represents the area situated between the territories supplied by the temporal and nasal posterior ciliary arteries. In the fluorescein angiographies of 800 normal subjects a watershed zone was not observed in 33.1% due to technical reasons and in 22.3% due to the simultaneous filling of the peripapillar and macular choriocapillaris. In the remaining 44.6% the watershed zone was well outlined: it was straddling the optic disc in about half of these cases and involved the temporal half of the optic disc and the close choroid in the other half. Very rarely the watershed zone involved the nasal half of the optic disc or the papillo-macular area. The position of the watershed zone could be important to explain the visual field defect in anterior ischemic optic neuropathy and glaucoma. PMID- 2583001 TI - [Non-histone chromatin proteins participating in the regulation of transcription of globin genes in erythroid cells]. PMID- 2582999 TI - Bilateral macular colobomas in Leber's congenital amaurosis. AB - Two siblings with Leber's congenital amaurosis had bilateral macular colobomas, nystagmus, extinguished ERGs, and degenerative salt and pepper like changes in the fundus. They had non-recordable or non-meaningful visually evoked cortical potentials in response to both flash and pattern stimuli. The ophthalmic conditions were thought to be inherited as an autosomal recessive trait. PMID- 2583002 TI - [The effect of adaptation of rats in ice water on their radiosensitivity]. PMID- 2583000 TI - Effect of botulinum toxin on extraocular muscle proprioception. AB - Injections of botulinum toxin type A (BoTox) in one extraocular muscle (EOM) induce long lasting paretic lengthening of the muscle permitting realignment to occur in strabismus, while eye movements appear to be unaffected after the transitory period of induced paresis. It has been hypothesized a BoTox-induced change in the spindle discharge of EOMs to explain the effect in EOM length. In decerebrate lambs and goats, first order neurons of eye muscle spindles were identified in a cellular pool located in the medial dorsolateral portion of the semilunar ganglion. The belly of the muscle to which the recorded unit belonged was infiltrated with BoTox. A decrease in afferent discharge of the spindle and in its stretch sensitivity was observed. This effect began 10-15 minutes after the injection. There was no corresponding decrease in muscle tension during the first 45 minutes. This finding suggests that the block of release of acetylcholine at motor endings is earlier and more efficacious in gamma- than in alpha-motoneurons. As a result of the proprioceptive input reduction, an unbalance between the agonist and antagonist muscles should occur favouring the ocular realignment. PMID- 2583003 TI - [Opposite changes of social behavior in hamadryas baboons after administration of mediators of cellular and humoral immunity--thymosine and myelopeptides]. PMID- 2583004 TI - [Attenuation of translation upon the use of alternative promotors of the gene for esterase S of Drosophila virilis]. PMID- 2583005 TI - [Features of the organization of the densovirus genome]. PMID- 2583007 TI - [Prevention of cigarette smoking in school. A prospective controlled study]. AB - 752 schoolchildren, mean age 12.7 years, were asked by multiple-choice questionnaire about their smoking experience. After this, eight educational lessons were given in seven of the schools ("intervention schools") to reinforce non-smoking. In six control schools no activities were performed. After 2.3 years, 579 schoolchildren (301 males and 278 females, mean age 15.0 years) again filled in a similar questionnaire. In the control schools 12.4% of children had begun to smoke, (greater than 1 cigarette per month), but only 7.4% in the intervention group (P less than 0.06). Daily cigarette smoking had been taken up by 8.4% in the control schools, but by only 4% in the intervention schools (P less than 0.04). 9.9% of children in the control schools and 3.8% in the intervention schools had smoked during the 24 hours before the questionnaire was filled in (P less than 0.004). The data indicate that an eight-hour course of instruction with reinforcement of non-smoking can lastingly influence smoking behaviour of juveniles. PMID- 2583006 TI - [Transpapillary cholangioscopy. A new diagnostic and therapeutic dimension]. AB - Transpapillary cholangioscopy (TCS) was performed in 52 patients (12 men, 40 women; mean age 61.6 [39-86] years) in whom endoscopic retrograde cholangiography had not provided a firm diagnosis. TCS was unsuccessful in five patients for technical or anatomical reasons. In 33 of the remaining 47 patients (70%) the procedure gave diagnostically or therapeutically useful results: In seven patients with tumour in the biliary tract biopsies were obtained, while in eight with extraductal stenoses cholangiography was made possible and provided the diagnosis. In eight patients residual gall stones were removed; in three cholangioscopically guided lithotripsy was successful. TCS proved to be a simple method with few complications; it significantly improved the diagnosis and treatment of diseases in the biliary tract. PMID- 2583008 TI - [Surgical masks--effective protection against cytostatic aerosols?]. AB - A surgical mask, a coarse-dust mask and five types of fine-dust masks were tested by enhanced light microscopy and cross-sectional thickness measurements for their effectiveness against inhalation of cytostatic aerosols. The construction of surgical masks most nearly resembles that of coarse-dust masks with respect to quality and number of layers. They are thus not suitable as protection against inhalation of cytostatic aerosols. Such masks must be at least particle-filtering half-masks of type DIN 58645 FHM - P2 (fine-dust masks of protective stage P2). PMID- 2583009 TI - [Intraoperative positional damage to the ulnar nerve in anatomic variants]. AB - After laparotomy (for acute abdomen) a 53-year-old woman had signs of pressure damage to the right ulnar nerve at the elbow. On open inspection at surgery 3 1/2 months later the rather deep right ulnar sulcus was markedly narrowed by connective tissue and the ulnar nerve thinned out; an epi- and perifascicular neurolysis was performed. There was no evidence of abnormal mobility of the left ulnar nerve. Nerve function gradually improved. Subsequent expert opinion concluded that adequate protective measures had been taken at the time of laparotomy to avoid positional or pressure damage to the nerve if the anatomy had been normal. - An abnormal mobility of a right ulnar nerve (it could be dislocated at the elbow) was demonstrated in a 35-year-old woman whose right ulnar nerve had been found to be damaged after laparotomy. It is recommended that, in the rare case in which such increased mobility is known preoperatively, the arm should be placed in supination with the elbow extended and carefully padded. PMID- 2583010 TI - [Are botanical immunostimulants effective and harmless?]. PMID- 2583011 TI - [Measuring the contribution of medical boards. Decision of the Bavarian Administrative Court on April 13, 1989]. PMID- 2583012 TI - [Influenza immunization]. PMID- 2583013 TI - [Antibiotics for Campylobacter pylori colonization of the stomach]. PMID- 2583014 TI - [Accidental vertebral body fracture]. PMID- 2583015 TI - [Intra-aortal balloon counterpulsation in acute myocardial infarction, ischemic left ventricle insufficiency and treatment refractory angina pectoris]. AB - Intraaortic balloon counterpulsation (IABP) was employed between 1977 and 1988 in 132 patients (37 women and 95 men; mean age 60 +/- 9.9 years) with coronary heart disease. Indications for IABP were cardiogenic shock in 93, markedly impaired left ventricular function in 13, and treatment-refractory angina in 26. The hospital mortality rate among those patients in cardiogenic shock was 54%. The mortality rate among the 47 patients who had additional procedures (percutaneous transluminal coronary angioplasty or operation) was 40%, significantly lower than that in 46 patients without further procedure (67%). Complications of IABP occurred in 20% of patients (bleeding, vascular injury, ischaemia in the legs, embolism or infection). The complication rate was, however, reduced to 10% in the last few years by improvements in placement technique and materials. Introduction and placement of the balloon catheter is simple, rapid and reliable. The initially high success rate is particularly valuable for those patients in whom further therapeutic measures can be undertaken. PMID- 2583016 TI - [Postoperative tetanus]. AB - 12 days after an operation for pericaecal abscess due to perforation of the appendix, a 57-year-old man developed severe tetanus requiring mechanical ventilation for 37 days. Additional complications--pneumonia with septicaemia, disseminated intravascular coagulopathy, prolonged renal failure--were controlled by intensive medical measures. The tetanus was most likely of endogenous origin: Clostridium tetani occurs as a saprophyte in the gastrointestinal tract. It is recommended that tetanus immunization status of a patient should be checked before any operation on the gastrointestinal tract. If negative, prophylactic tetanus antitoxin should be administered. PMID- 2583017 TI - [Erythrohepatic protoporphyria with rapidly progressing liver cirrhosis]. AB - A 49-year-old man, known to have had an increased light sensitivity since childhood, was admitted to hospital because of jaundice. Biochemical and morphological examination revealed cirrhosis of the liver with cholestasis. There was a 70-fold increase of protoporphyrin content in the erythrocytes, increased fecal protoporphyrin excretion as well as secondary coproporphyrinuria. Despite symptomatic treatment with ursodeoxycholic acid and cholestyramine hepatic failure ensued for which orthotopic liver transplantation was performed five months after the diagnosis had been made. The patient died two months later of treatment-resistant septicaemia and multiorgan failure. This case demonstrates the need for annual monitoring of liver functions and porphyrin parameters to ensure earliest possible diagnosis of hepatic involvement in erythrohepatic protoporphyria. PMID- 2583018 TI - [Thrombocytopenia and surgical intervention]. PMID- 2583020 TI - [Catheter break in an implantable central venous infusion system with embolization in the pulmonary artery]. AB - A central venous catheter with a subcutaneous infusion port was implanted for chemotherapy into a 64-year-old woman with gastric lymphoma. Six weeks later, two weeks after a trivial trauma with hyperextension of the shoulder joint, it was found that the catheter had broken and its tip portion had embolized into the pulmonary artery: it was retrieved without difficulty via the femoral vein. This event suggests that pressure between clavicle and first rib can cause material fatigue in a silicon catheter. Such catheters should therefore not be implanted via the subclavian vein. PMID- 2583019 TI - [Circulatory collapse caused by carbachol-containing eye drops]. PMID- 2583021 TI - [Endocarditis prevention following rheumatic fever?]. PMID- 2583022 TI - [Spirochetal bacteria as the cause of gastritis?]. PMID- 2583023 TI - [Case description of a congenital malformation in a calf, characterized by an ingrowth of the fetal membranes into the cranial cavity]. AB - It is reported on a congenital malformation at the head of a calf born dead, characterized by downgrowth of the fetal membranes into the cranial cavity. The outer appearance and the pathologic-anatomical observations are presented in pictures and the attempt of an interpretation is made. PMID- 2583024 TI - [The compatibility of the new ionophore-coccidiostats with other chemotherapeutics in broilers]. AB - The compatibility of Salinomycin, Narasin or Maduramycin with Tiamulin, Erythromycin, Tylosin, Kitasamycin, Flumequine, Sulfachlorpyrazine or Sulfaquinoxaline was tested in cockerels in three experiments. It was found that Salinomycin and Narasin are incompatible with Tiamulin, Erythromycin, Sulfachlorpyrazine and Sulfaquinoxaline. The effect of incompatibility was shown more markedly with the administration of Salinomycin than with Narasin. Maduramycin was also shown as incompatible with Tiamulin although this interaction was nowhere near as severe as in the case of Salinomycin or Narasin. It caused a significant weight gain depression without mortality. Because of the significant weight gain depression, however, the administration of Tiamulin in the presence of Maduramycin in feed will not be recommended. At the same time, Maduramycin proved to be fully compatible with Erythromycin, Sulfachlorpyrazine and Sulfaquinoxaline. All three anticoccidials tested showed total compatibility with Tylosin, Kitasamycin and Flumequine. PMID- 2583026 TI - [Dispensing law and sale of animal feed]. AB - For the veterinarian, drug sale is generally permitted by his licence of drug dispensing. According to the law on animal feed, feedstuffs are not regarded as drugs and thus they are not licensed to be sold by veterinarians. Drugs, however, may only be released for the treatment of individual animals, which are previously examined by the vet. The sale of animal feed is not regarded as part of veterinary practice. Only in case of a registered additional business, a veterinarian is allowed to sale feedstuffs. Dietetic animal feedstuffs are also regulated by the Animal Feed Act. Dietetic drugs, however, are regulated by the Drug Act and are strongly to be delineated from dietetic feed. Thus, the term "dietetic" alone does not automatically give any legitimatization for a sale of feedstuffs in veterinary practice. PMID- 2583025 TI - [Scanning electron and light microscopic studies of the surface epithelium of the rete testis and epididymis in the boar. II. Ductus epididymis]. AB - The entire ductus epididymidis is characterized by pseudostratified columnar epithelium which contain principal and basal cells. Apical cells are found in the proximal segments. Long stereocilia projected from the apical surface of the principal cells. Signs of adjacent apocrine secretory activity are shown. The various segments of the ductus epididymidis present differences in the height of the epithelium, the development of the stereocilia, the appearance of granules in the cytoplasm, the luminal sperm concentration and the height of the peritubular layer. PMID- 2583027 TI - [Drug sensitivity of haemophilus influenzae type b:n]. PMID- 2583028 TI - Traditional and new treatment strategies for oral squamous cell carcinomas. AB - 308 patients with intraoral carcinomas were treated in the Finsen Institute, Copenhagen, from 1978 to 1982. As primary treatment, 73% of the patients had radiotherapy alone, 5% had operations alone, and 14% had combined treatment. After first recurrences, 45% of 204 patients were operated on. This treatment strategy kept 40% of all 308 patients free of disease for at least 3.5 years or until death. Fifty-eight percent of all 308 patients died of their oral carcinomas. The present study shows that tumor size, lymph node involvement, and total tumor stage are important prognostic factors. Old and new treatment strategies are discussed and more use of operations using modern reconstructive techniques followed by radiotherapy is recommended. PMID- 2583029 TI - Invasive basal cell carcinoma of the temporal bone. AB - Basal cell carcinomas involving the ear represent a spectrum of diseases, from a small superficial auricular lesion to an advanced destructive malignancy invading the temporal bone. The biologic activity of the morphea-form basal cell carcinoma variant of tumor and a postauricular location predispose to an aggressive biologic pattern. Management requires a thorough evaluation with determination of the degree of cranial and possible intracranial invasion. These lesions usually can be managed with partial temporal bone resections, although prognosis for patients with advanced lesions may be poor. PMID- 2583030 TI - Invasive intramuscular hemangiomas of the head and neck. AB - Intramuscular hemangiomas make up less than 1% of all hemangiomas [1]. These invasive and aggressive lesions appear to have a predilection for large muscle masses. They can be strikingly aggressive in the head and neck, and persistence despite radical treatment is common. Spontaneous resolution in adults to our knowledge has not been reported in the literature. We present a case report of an invasive intramuscular hemangioma involving the parotid gland, the masseter and pterygoid muscles, and the infratemporal fossa after local resection of an apparently isolated lesion of the lip and the submandibular triangle. We describe a detailed course of treatment and review the literature. PMID- 2583031 TI - Calcification and thyroid carcinoma. PMID- 2583032 TI - Epithelial retention cyst of the neck after chest flap reconstruction. PMID- 2583033 TI - Nipping "malignant" otitis externa in the bud? PMID- 2583034 TI - Mycobacterial cervical lymphadenitis. AB - Mycobacterial cervical lymphadenitis remains a diagnostic challenge for many clinicians despite current advances in diagnostic laboratory techniques. Although much has been done to prevent tuberculosis, cases of mycobacterial disease in endemic form still occur. Six hundred and forty-five patients with tuberculosis were diagnosed and treated at the American University of Beirut Medical Center during the period from 1970 to 1985. Twenty-nine (4.5%) of these patients had proven mycobacterial cervical lymphadenitis. We stress histopathologic examination as the single most important means for diagnosing mycobacterial cervical lymphadenitis. Operation in combination with antituberculous chemotherapy remain the treatments of choice. PMID- 2583035 TI - Auricular wedge resection and reconstruction. AB - Various techniques have been described in the literature for auricular reconstruction after resection of both benign and malignant tumors of the auricle. Since 1981, I have performed simple wedge resections of the auricle as treatment for both basal and squamous cell carcinomas. A 4-mm margin on the former lesions and a 6-mm margin on the latter lesions have been used routinely. Thirty patients so treated were studied. The follow-up period for most of the patients was a minimum of one year, and only 1 patient had a recurrent lesion, which was resected without complication. The size of the lesions ranged from 4 mm to 3 cm. The majority of the lesions were either basal or squamous cell carcinomas (other lesions included melanomas, fibrous histiocytomas, and chondrodermatitis nodularis chronica helices), and multiple frozen sections of the margins resected were carefully examined. The technique of reconstruction using polyglactin 910 sutures on the cartilage and a molded otoplasty dressing contributed to a good cosmetic result for all patients. PMID- 2583036 TI - Postirradiation sarcomas of the head and neck. AB - We discuss four cases of postirradiation sarcomas of the head and neck. Two cases were metachronous sarcomas that appeared after operation and irradiation for primary sarcomas, 1 case was a mandibular malignant fibrous histiocytoma that developed on the opposite side of the jaw from a malignant histiocytic neoplasm that was irradiated 8 years previously, and 1 case was a laryngeal tumor that appeared 5 years after combined operative and radiation therapy for a laryngeal squamous carcinoma. Immunohistochemical studies more precisely defined and classified these tumors, and assisted in determining a therapeutic protocol. The therapy for postirradiation sarcomas includes extirpative operation when possible, but the role of chemotherapy is uncertain. The aggressive behavior of these neoplasms was attested to by the death of three patients within 18 months of their operations. PMID- 2583038 TI - Quincke's disease after acetaminophen use. PMID- 2583037 TI - Primary tuberculosis of the tongue. AB - Primary tongue tuberculosis is an uncommon condition, and there is a paucity of such cases in the literature. We report a case of primary tuberculosis of the tongue in a 55-year-old man. PMID- 2583040 TI - The relevance of endocrinology to a national research program. PMID- 2583039 TI - Is ultrasound treatment beneficial in Bell's palsy? PMID- 2583041 TI - Enterohepatic circulation of triiodothyronine (T3) in rats: importance of the microflora for the liberation and reabsorption of T3 from biliary T3 conjugates. AB - In normal rats, T3 glucuronide (T3G) is the major biliary T3 metabolite, but excretion of T3 sulfate (T3S) is greatly increased after inhibition of type I deiodinase, e.g. with 6-propyl-2-thiouracil (PTU). In this study, the fate of the T3 conjugates excreted with bile was studied to assess the significance of a putative enterohepatic circulation of T3 in rats. Conventional (CV) or intestine decontaminated (ID) rats received iv [125I]T3G or [125I]T3S, the latter usually after pretreatment with PTU (1 mg/100 g BW). Radioactivity in plasma and bile or feces was analyzed by Sephadex LH-20 chromatography and HPLC. Within 1 h, 88% of injected T3G was excreted in bile of CV or ID rats, independent of PTU. About 75% of the injected T3S was excreted within 4 h in PTU-treated rats, in contrast to only 20% in controls. Up to 13 h after iv administration of T3G or T3S (+PTU) to intact ID and CV rats, fecal radioactivity consisted of more than 90% T3 in all CV rats, 95% of T3S in T3S-injected ID rats, and 30% T3 and 67% T3G in T3G injected ID rats. In overnight-fasted CV rats injected with T3G, total plasma radioactivity rapidly declined until a nadir of 0.10% dose/ml at about 2.5 h, but radioactivity reappeared with a broad maximum of 0.12% dose/ml between 5.5-10 h. In the latter phase, plasma radioactivity consisted of predominantly I- and T3 in a ratio of 2:1. Reabsorption was diminished in fed CV rats and prevented in ID rats. Plasma T3 4-10 h after iv T3G injection to overnight-fasted CV rats was 12, 2, and 3 times higher than that in bile-diverted rats, fed CV rats, and ID rats, respectively, and similar to that 4 h after the injection of T3 itself. Total plasma radioactivity as well as plasma T3 6-13 h after iv administration T3S in PTU-treated rats were significantly increased in CV vs. ID rats, e.g. T3 0.016% vs. 0.005% dose/ml. These results demonstrate a significant enterohepatic circulation of T3 in rats in which bacterial hydrolysis of T3 conjugates excreted with bile plays an important role. PMID- 2583042 TI - Bromocriptine microcapsules inhibit ornithine decarboxylase activity induced by Freund's complete adjuvant in lymphoid tissues of male rats. AB - Arthritis is produced in male rats within 9-10 days after a single injection of Freund's complete adjuvant (FCA) at the base of the tail. When bromocriptine, a dopaminomimetic that suppresses PRL secretion, was given in form of long-acting microcapsules (CBLA) 3 days before FCA, the hind limb swelling was significantly reduced by 70%. Here, we showed that plasma PRL levels were significantly elevated (by 150% over controls) during the 6-day period after FCA, particularly at night. Further, within 1-4 days after FCA inoculation, marked increases in ornithine decarboxylase (ODC) activity occurred in bone marrow, thymus, spleen, and lymph nodes (by 190%, 160%, 80% and 75% over control values, respectively). In FCA-treated rats, the circadian rhythm of thymic ODC showed that an important enhancement of activity occurred during the dark phase, which correlated with the peak of PRL secretion (between 2200-0400 h). Finally, pretreatment with CBLA significantly inhibited the induction of ODC in response to FCA in thymus, spleen, and lymph nodes (by 65%, 80%, and 45%, respectively) and inhibited it more weakly in the bone marrow. This in vivo study leaves little doubt about the existence of a PRL-dependent immuno-stimulatory mechanism, probably involved in the pathogenesis of adjuvant arthritis. PMID- 2583043 TI - The regulation of lipogenesis by thyroid hormone and its contribution to thermogenesis. AB - We have used the tritiated water method to quantitate the effects of thyroid hormone on lipogenesis in the rat and then determined the contribution of this process to thyroid hormone-induced thermogenesis. After thyroid hormone administration to hypothyroid animals, fatty acid synthesis rose after a lag time of 12-16 h and reached a plateau after 4-5 days. This is consistent with the kinetics of an increase in oxygen consumption measured by others in similar animals. A diurnal variation was maintained in all thyroid states, with the peak value in the middle of the dark period being 3-fold higher than the nadir. Fatty acid synthesis in the livers of hyperthyroid animals was 3- to 4-fold higher than that in euthyroid rats, which, in turn, was 3- to 5-fold higher than the rate observed in hypothyroid rats. Slightly smaller but similar fold increases were measured in epididymal fat. A stimulation of fatty acid synthesis by thyroid hormone was also measured in the rest of the carcass, with hyperthyroid rates being twice those in hypothyroid animals. The contribution of the liver was much greater in hyperthyroid rats (34% of total fatty acid synthesis) than in hypothyroid animals (5%). The energy costs of this synthesis were calculated and compared to published values for total oxygen consumption in different thyroid states. Thus, 6-10% of the total increment in oxygen consumption between hyperthyroid and hypothyroid animals could be attributed to lipogenesis, depending on which published figures were used. About 3% of this increment was due to the liver alone. PMID- 2583045 TI - Lesions to the anterior hypothalamus prevent the melatonin-induced lengthening of delayed implantation. AB - The anterior hypothalamic area (AHA) has been postulated as a site of action for melatonin. We tested the hypothesis that lesions to the AHA (AHAx) would counteract the inhibitory effect of exogenous melatonin on blastocyst implantation in the spotted skunk by removing a possible site of action. Forty seven females were treated as follows during delayed implantation. In Exp 1, five received empty Silastic capsules, five received Silastic capsules containing melatonin, six received sham AHAx plus empty capsules, none received AHAx plus empty capsules, and eight received AHAx plus capsules containing melatonin. In Exp 2, four skunks each received two empty capsules, five skunks each received two capsules containing melatonin, and five skunks received AHAx plus capsules containing melatonin. All capsules were inserted sc in the interscapular region 14-35 days after surgery in Exp 1 and 2 weeks before surgery in Exp 2. Surgery was performed between January 22 and February 12, 1988, in Exp 1 and on March 2 3, 1989, in Exp 2. The skunks were subjected to a natural photoperiod, and the duration of preimplantation was measured. In Exp 1, AHAx plus empty capsules significantly (P less than 0.05) shortened the duration of preimplantation (163 +/- 14.7 days) compared to that in sham AHAx or intact controls (193 +/- 26.1 and 188 +/- 10.6 days, respectively). Melatonin significantly (P less than 0.05) prolonged the duration of preimplantation (289 +/- 2.9 days) in intact skunks, but failed to do so in skunks with AHAx, as the preimplantation period was significantly shortened (159 +/- 6.1 days). In Exp 2, AHAx reversed the inhibitory effect of melatonin on the duration of preimplantation (191 +/- 21.5 days), as intact melatonin-treated skunks had a significantly longer preimplantation period (260 +/- 2.5 days) than skunks receiving empty capsules (191 +/- 16.4 days). The inhibitory effect of melatonin was reversible in all intact skunks, as blastocysts implanted 23 days, on the average, after cessation of treatment with melatonin. These data are consistent with the hypothesis that a portion of the AHA and/or adjacent regions play an essential role in timing blastocyst implantation in the spotted skunk. The lesions may have given this result by ablating a neural pathway controlling PRL secretion and may or may not have involved a site of action for melatonin. PMID- 2583044 TI - Developmental pattern of estrogen receptor expression in female mouse genital tracts. AB - The distribution of the estrogen receptor (ER) was investigated in neonatal female genital tracts (uterus, oviduct, cervix, and vagina) from days 1-22 after birth, using immunohistochemistry employing an anti-ER monoclonal antibody. In uteri, the ER in epithelial cells began to be observed by day 4. The number of positive epithelial cells and the staining intensity gradually increased until day 22 of age. On the other hand, uterine stroma cells gave a strong ER immunostaining even on day 1. The staining intensity reached a maximum by days 4 7 and then slightly decreased with age. In the oviduct, cervix, and vagina, epithelial cells showed positive ER immunostaining on day 1, and the intensity increased gradually until day 22. ER immunostaining in stroma cells was almost constant during the development period. The ER in both epithelial and stroma cells from these younger animals showed similar biochemical properties, i.e. an increased affinity for nuclei and resistance to extraction with PBS. Thus, during neonatal development of the female reproductive tract, ER is present not only in stroma cells but also in epithelial cells. This ER protein exhibits properties and characteristics similar to those of adult mice. The presence of ER suggests that some of the estrogen actions of cell proliferation, differentiation, and tissue abnormalities resulting from prenatal and postnatal estrogen administration may be mediated by receptor interactions. PMID- 2583046 TI - Thyroid hormone and growth hormone interact to regulate insulin-like growth factor-I messenger ribonucleic acid and circulating levels in the rat. AB - Thyroid hormones influence growth in part by altering the secretion and effects of GH. GH, in turn, mediates its effects by regulating the synthesis and secretion of insulin-like growth factor-I (IGF-I). IGF-I is a pleiotropic growth factor that is synthesized by many tissues and acts on many tissues to regulate both cellular replication and differentiated function. We have studied the direct effects of thyroid hormones and the combined effects of thyroid hormones and GH on the regulation of IGF-I synthesis and secretion in hypophysectomized (hypox) rats in vivo. All rats, except normal littermates and a hypox control group, received 100 micrograms hydrocortisone/100 g BW for 10 days. Circulating IGF-I was measured by specific RIA (normal rats, 1 U/ml), and hepatic IGF-I mRNA was measured by Northern blot hybridization with an antisense cRNA probe. 1) Hypox rats treated with hGH (75 micrograms, ip, twice daily) for 10 days gained 17 g BW vs. 70 g for normal littermates. GH markedly increased hepatic IGF-I mRNA and circulating IGF-I (0.52 +/- 0.14 U/ml 12 h after the last GH injection vs. 0.03 +/- 0.02 for hypox controls). 2) T4 (1 micrograms/100 g BW, ip) for 10 days increased neither weight, hepatic IGF-I mRNA, nor circulating IGF-I. 3) Rats treated with T4 for 10 days followed by a single injection of 1 mg GH, ip, increased hepatic IGF-I mRNA and circulating IGF-I levels comparably as in rats receiving acute GH alone (IGF-I, 12 h, 0.31 +/- 0.09 vs. 0.36 +/- 0.06 U/ml). 4) Hypox rats treated with a single injection of T3 (1.5 micrograms/100 g BW, ip) had slightly increased hepatic IGF-I mRNA, but showed no significant change in circulating IGF-I levels. 5) A single injection of T3 plus GH to hypox rats increased IGF-I mRNA levels above those in rats injected with GH alone and increased serum IGF-I levels to 0.48 +/- 0.12 U/ml compared to 0.36 +/- 0.06 U/ml for GH alone. 6) After 10 days of GH treatment, a single injection of T3 lowered both hepatic IGF-I mRNA and circulating IGF-I (0.52 +/- 0.14 to 0.16 +/- 0.06 U/ml, 6 h after T3). These studies demonstrate that thyroid hormones have relatively little direct effect on IGF-I synthesis but can have major effects on GH-stimulated IGF-I synthesis and secretion. The pattern of these effects depends on the integrity of the pituitary gland, prior exposure of the liver to GH and/or thyroid hormones, and the temporal relationship between GH and thyroid hormone administration. PMID- 2583047 TI - High density lipoprotein3 binding and biological action: high affinity binding is not necessary for stimulation of placental lactogen release from trophoblast cells. AB - High density lipoprotein (HDL3) binds with high affinity to many types of cells, but controversy exists concerning the nature and biological significance of the binding. We have recently demonstrated that HDL and apoproteins (apo)-AI, -AII, and -CI stimulate a specific and dose-dependent increase in placental lactogen (hPL) release from human trophoblast cells. To examine the possible relationship between HDL3 binding and stimulation of hPL release, we have characterized the binding of [125I]HDL3 to an enriched fraction of hPL-producing trophoblast cells. Binding studies were performed on trophoblast cells isolated by isopycnic centrifugation of collagenase/hyaluronidase-dispersed placental tissue and apo-E free-HDL3 (density, 1.125-1.215 g/ml). Scatchard analysis of binding studies performed at 37 C for 2 h revealed two classes of binding sites: 1) high affinity binding sites with a Kd of 9.7 +/- 2.2 micrograms/ml (1.3 x 10(-7) M) and 9.8 +/- 3.2 x 10(5) binding sites/trophoblast cell, and 2) low affinity binding sites with a Kd of 172.8 +/- 64.8 micrograms/ml (2.3 x 10(-6) M) and an estimated 3.2 x 10(6) sites/cell. As has been found in hepatocytes and other cells, the number of HDL3-binding sites per trophoblast cell (but not the binding affinity) decreased at lower incubation temperatures. In addition, HDL3 binding to trophoblasts cells did not require calcium and was not affected by prior treatment of the cells with pronase or trypsin. HDL3-binding sites on trophoblast cells, however, were not specific for HDL3. Low density lipoprotein (density, 1.063-1.055 g/ml), which does not stimulate hPL release, was nearly as potent on a molar basis as HDL3 in binding to the high and low affinity binding sites on trophoblast cells. Furthermore, nitrated HDL3, which does not compete for high affinity binding to trophoblast cells, stimulated hPL release. Although the characteristics of HDL3 binding to trophoblast cells are similar to those of other cells, these results strongly suggest that the binding of HDL3 to high affinity binding sites is not essential for HDL-mediated hPL release. PMID- 2583048 TI - The pharmacokinetics and pharmacodynamics of a human relaxin in the mouse pubic symphysis bioassay. AB - The effects of dose, route, regimen, and the presence or absence of a repository vehicle [benzopurpurine (BPP)] were determined for a human relaxin (hRlx) in the mouse pubic symphysis bioassay. Administration of 88 micrograms/kg hRlx sc in 1% BPP resulted in delayed, prolonged absorption. Although peak hRlx concentrations were lower, serum concentrations remained elevated longer in the presence of BPP compared to a single sc administration of hRlx in saline at the same dose. The bioavailabilities with and without BPP were similar (109 and 96%, respectively). While the pharmacodynamic effect (i.e. lengthening of the pubic ligament in estrogen-primed mice) was approximately maximum at 88 micrograms/kg hRlx sc with BPP, single sc administration of hRlx without BPP up to 264 micrograms/kg had no effect on pubic ligament length. In the absence of the BPP vehicle, manipulation of the regimen (e.g. multiple sc doses) showed that emulation of the serum concentration-time profile observed for hRlx in the presence of BPP resulted in similar pharmacodynamic effects. It appears that BPP delays the absorption of hRlx after sc administration, resulting in prolonged, elevated hRlx serum concentrations. hRlx has been shown to be effective in this model without BPP if it is administered by a multidose sc schedule. As has been observed with other protein therapeutics, the dosage regimen employed for hRlx delivery appears to be an important determinant of the expression of its pharmacodynamic effects. PMID- 2583049 TI - Vasoactive intestinal peptide potentiates sexual behavior: inhibition by novel antagonist. AB - Vasoactive intestinal peptide (VIP) has been suggested as a neurotransmitter mediating penile erection. We now show that VIP can stimulate sexual behavior in rats with reduced masculine potential due to pituitary grafting or castration. This effect was attenuated in the presence of a novel VIP antagonist, devised by a hybrid peptide strategy. Thus, we have synthesized a molecule combining a portion of VIP with a portion of neurotensin, peptides of opposite pharmacological action on cAMP formation and smooth muscle relaxation. The hybrid peptide markedly inhibited VIP's effect on sexual behavior. This inhibition was manifested by a significant increase in the mean interval between copulatory events (greater than 3-fold change) coupled with a blockade of VIP-stimulated ejaculation. Other putative VIP antagonists were not as effective in blocking these activities. Thus, our results imply that VIP is not only associated with penile erection, but is involved in sexual behavior as well. Furthermore, the hybrid antagonist was shown to inhibit VIP binding in glial cell cultures. The availability of highly potent VIP antagonists may offer a route to study the possible multiple VIP receptors as well as help delineate other biological activities attributable to VIP. PMID- 2583050 TI - Expression of calbindin-D decreases with age in intestine and kidney. AB - The calbindins are Ca-binding proteins whose expression is regulated by 1,25 dihydroxyvitamin D3, the active metabolite of vitamin D3. The calbindins are found in high amounts in the proximal intestine (calbindin-D-9k) and the kidney (calbindin-D-28k), and they are thought to play a role in Ca transport by these tissues. Ca absorption by the intestine and perhaps the kidney declines with age, and this could be due to decreased expression of calbindin. Therefore, the expression of calbindins-D-9k and -D-28k was measured in F344 rats aged 2, 6, 13, and 24 months. mRNA levels were measured by dot blot hybridization to synthetic cDNA oligonucleotide probes, and protein levels were measured by enzyme-linked immunosorbent assay using specific antisera. Intestinal calbindin-D-9k mRNA decreased markedly between 2 and 6 months of age, but it then increased significantly between 13 and 24 months. Calbindin-D-9k protein paralleled the decrease in mRNA between 2 and 6 months, but continued to decline at 13 and 24 months despite the rise in mRNA. In the kidney, calbindin-D-28k mRNA declined between 2 and 13 months and then plateaued. Calbindin-D-28k protein followed a similar pattern. In the same studies expression of calmodulin by the intestine and kidney did not change with age. Plasma 1,25-dihydroxyvitamin-D3 correlated well with the expression of calbindin-D-9k in the intestine at 2 and 6 months of age and with the expression of calbindin-D-28k in the kidney at all ages. Decreased expression of calbindin-D with age may contribute to the age-related decrease in Ca transport in intestine and kidney. PMID- 2583051 TI - Hormonal control of the cervix in pregnant gilts. I. Changes in the physical properties of the cervix correlate temporally with elevated serum levels of estrogen and relaxin. AB - The time course of changes in the physical properties of both the uterine and vaginal portions of the cervix were studied during the last two thirds (days 40 to approximately 115) of pregnancy in the gilt. To obtain insight concerning the hormonal control of these physical changes, serum levels of relaxin, estrone, 17 beta-estradiol, and progesterone were also determined. Throughout midpregnancy, the extensibility (softness), lumen diameter, and wet weight of the uterine portion of the cervix were less than those of the vaginal portion of the cervix. After day 80, marked and sustained increases in these three physical parameters occurred in the uterine portion of the cervix whereas slight (extensibility) or moderate (lumen diameter and wet weight) increases occurred in the vaginal portion of the cervix. By day 110, extensibility, lumen diameter, and wet weight of the uterine portion of the cervix were similar to those of the vaginal portion of the cervix. Because the uterine portion of the cervix has a relatively firm consistency and small lumen throughout most of pregnancy, we conclude that it probably plays a more important role than the vaginal portion of the cervix in protecting the uterus and its contents during pregnancy. The marked changes in the physical properties of the uterine portion of the cervix are temporally correlated with elevated serum estrogen levels (days 80-100) or estrogen and relaxin levels (day 100 to term). We conclude that estrogen or, more likely, estrogen and relaxin in combination may promote the modifications in the physical properties of the cervix that occur during the last 35 days of gestation. PMID- 2583053 TI - Aldosterone metabolism in the isolated perfused liver of female and male rats. AB - A sex-dependent metabolism of aldosterone has been reported in intact rats. To further characterize the hepatic elimination of aldosterone and its sex dependence, the metabolism of d-[4-14C]aldosterone was studied in isolated perfused liver from male and female Wistar rats, from male rats castrated 3 weeks before experiments, and from younger male rats (same body weight as the female rats). The livers were perfused at a constant flow rate in a recirculating mode with a hemoglobin-free medium containing aldosterone at initially 1 nM. Perfusate aldosterone was measured by a specific RIA. Total 4-14C radio-activity in perfusate and bile was determined. The perfusate [4-14C]aldosterone radiometabolite concentration was calculated. The radiometabolite pattern in additional experiments was studied by HPLC. The male rats exhibited 10% higher systolic blood pressure (P less than 0.05) and 51% higher fasting values of plasma aldosterone (P less than 0.05) compared to those in the female rats. In female rats the hepatic clearance rate of aldosterone per 100 g BW was 72% higher than that in male rats (11.2 +/- 2.7 to 6.5 +/- 1.8 ml/min: P less than 0.01), and that expressed per g liver wet wt was 75% higher (3.5 +/- 1.0 to 2.0 +/- 0.7 ml/min; P less than 0.01). When female rats were compared to younger male rats with the same body weight, 33% higher hepatic aldosterone clearance rates were still found in female rats (21.0 +/- 5.4 to 15.8 +/- 3.2 ml/min; P less than 0.05), and 51% higher values when expressed per g liver wet wt (3.5 +/- 1.0 to 2.3 +/- 0.5 ml/min; P less than 0.01). No difference in the aldosterone clearance rate was observed in castrated male rats compared to that in noncastrated male rats. 4-14C-Labeled radiometabolite levels accumulated similarly in the perfusate of livers of both sexes. Perfusate 4-14C-labeled radiometabolites after 90 min of perfusion were lower in livers of castrated male rats than in noncastrated male rats (P less than 0.001). The final perfusate 14C-labeled radiometabolite concentration correlated inversely with the total 14C in bile (P less than 0.01). All 14C-labeled radiometabolites detected in perfusate and bile after 90 min were more polar than aldosterone. After enzymatic hydrolysis, some of the metabolites from the male livers cochromatographed with tetrahydro- and dihydroaldosterone, while other fractions remained more polar. Only more polar metabolites were detected in the perfusate and bile of female livers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2583052 TI - Hormonal control of the cervix in pregnant gilts. II. Relaxin promotes changes in the physical properties of the cervix in ovariectomized hormone-treated pregnant gilts. AB - The effects of relaxin on the physical properties of both the uterine and vaginal portions of the cervix were studied between days 80 and 110 of pregnancy in ovariectomized gilts given progesterone to maintain pregnancy. In controls gilts the extensibility, lumen diameter, and wet weight of the uterine portion of the cervix were less than those of the vaginal portion of the cervix on day 80, but increased thereafter, and by day 110 did not differ (extensibility and wet weight) or approached (lumen diameter) those values of the vaginal portion of the cervix. When gilts were ovariectomized on either days 80 or 100 and given progesterone only (groups OP-100 and OP-110) extensibility, lumen diameter, and wet weight failed to increase in both the uterine and vaginal portions of the cervix. After replacement therapy with progesterone plus relaxin (groups OPR-100 and OPR-110), extensibility, lumen diameter, and wet weight increased to values as least as large as those in control groups in both portions of the cervix. In all groups the uterine portion of the cervix changed more dramatically than the vaginal portion. After hormone replacement therapy, blood levels of relaxin were moderately higher, and blood levels of progesterone were somewhat lower than those in control gilts. There was little or no difference in estrogen levels between ovariectomized and control gilts. We conclude that relaxin plays an important role in promoting increased growth and extensibility in both the uterine and vaginal portions of the cervix after day 80 of gestation in the gilt. PMID- 2583054 TI - Hormone-dependent regulation of chicken progesterone receptor deoxyribonucleic acid binding and phosphorylation. AB - To further understand the structure-function relationships of the chicken oviduct progesterone receptor, the effects of in vivo and in situ progesterone treatment were studied. Immunoprecipitated receptors isolated from oviduct slices incubated in the presence of H(3)32PO4 exhibited hormone-dependent phosphorylation. This was correlated with an increase in the apparent mol wt of receptors when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and increased DNA binding of total cytosolic receptors. Further, in vivo progesterone treatment resulted in dissociation of both the A and B receptor forms from nonhormone binding proteins (such as heat shock protein-90) in vitro when analyzed by sucrose gradient ultracentrifugation. The 4S and 8S receptors were separated by phosphocellulose column chromatography, treated with ammonium sulfate to convert all receptors to DNA-binding forms, and analyzed for binding to DNA cellulose. The 4S receptor produced as a consequence of in vivo hormone treatment had a 3.35 fold higher affinity for DNA and bound to about a 3-fold greater extent than receptor that did not show altered interaction with other proteins. Thus, in vivo progesterone treatment results in increased receptor phosphorylation, altered interaction with heat shock protein-90, and increased DNA binding. PMID- 2583055 TI - Location of the second steroid-binding site on the glucocorticoid receptor. AB - The ability of nonradioactive progesterone to accelerate the dissociation of tritiated dexamethasone from the agonist-binding site of the glucocorticoid receptor was used as a probe for the existence of a second antagonist steroid site. The goal was to evaluate if this second site was on the glucocorticoid receptor and, if so, on what region of that protein. The magnitude of acceleration of dissociation was assessed during purification of the receptor as well as with the untransformed (multimeric), transformed (monomeric), and mero receptor. In each preparation progesterone caused a statistically significant increase in the rate of agonist dissociation. The documentation of acceleration of dissociation during purification suggests that progesterone one is interacting with a site on the glucocorticoid receptor and not with another protein. Evidence for the second binding site was found using each form of the receptor, untransformed, transformed, and mero-receptor, suggesting that the second binding site resides on the steroid-binding domain of the receptor which is on the carboxy-terminus, topographically close to the agonist-binding site. PMID- 2583056 TI - Analysis of overall pathophysiological relationships between serum levels of TSH and thyroid hormones using a large laboratory database. AB - Factors associated with the basal level of serum thyrotropin (TSH) were analyzed over a wide range of pathophysiological conditions by means of a large laboratory database on thyroid function. When data were analyzed two-dimensionally, serum TSH showed significant inverse correlations with total triiodothyronine (T3), free T3 index (FT3I), total thyroxin (TT4) and free T4 index (FT4I) in the order of increasing intensity. The three-dimensional analysis, however, revealed that 1) total hormone levels were actually unrelated to serum TSH when the levels of free hormone indices were held constant, 2) the relation between FT3I and TSH became obscure when the influence of FT4I was similarly removed. On the other hand, 3) the relation of FT4I with TSH was unaffected by the level of FT3I. These results suggest that free T4 is the main determinant of the serum TSH level. This study also implies that it is possible to use large amounts of laboratory data to elucidate the overall profile of a given patho-physiological system, whose structure is only partially revealed by conventional clinical or animal studies. PMID- 2583057 TI - Incidences of antibodies to Yersinia enterocolitica: high incidence of serotype O5 in autoimmune thyroid diseases in Japan. AB - Antibodies to Yersinia enterocolitica serotype O3, O5, O6 and O9 were measured by the micro-agglutination method in 445 healthy subjects and patients with Grave's disease (n = 70), Hashimoto's disease (n = 45) and thyroid tumor (n = 29). In contrast to previous reports, the incidence of antibodies to serotype O3 in each group of patients with thyroid diseases was not significantly different from that in healthy subjects. However, the incidence of antibodies to serotype O5 was significantly higher in patients with Graves' disease (81.4%, P less than 0.001) and Hashimoto's disease (91.1%, P less than 0.001) than in healthy subjects (258.9%). Significantly increased incidence of antibodies to serotypes O6 and O9 was observed only in patients with Hashimoto's disease (40.0% and 51.1% vs healthy subjects 24.7% and 29.9%, respectively). Patients with thyroid tumor showed no increase in any serotype of Yersinia enterocolitica. No correlations was found between the titers of anti-Yersinia antibodies and anti-thyroglobulin or anti-microsomal antibodies. These data indicate an association between thyroid autoimmunity and antibodies to Yersinia enterocolitica. These results are different from those in reports from other countries, suggesting that serotype specificity may be influenced by racial or genetic factors. PMID- 2583058 TI - Inhibition of rat ovarian 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17 alpha-hydroxylase and 17,20 lyase by progestins and danazol. AB - The site of action of synthetic progestins or danazol in the treatment of endometriosis is considered to be mainly the hypothalamo-pituitary level, but the direct action to the uterine endometrium and the ovary is also suggested. We investigated the effect of these synthetic steroids to rat ovarian steroidogenic enzymes. The effect of norethisterone, levonorgestrel, danazol, gestrinone, desogestrel and 3-keto-desogestrel was studied in vitro. The sources of the enzymes were prepared from ovaries of immature rats treated either with pregnant mare serum gonadotropin (PMS) and human chorionic gonadotropin (hCG) for 3 beta hydroxy steroid dehydrogenase (3 beta-HSD), or with PMS for 17 alpha-hydroxylase and 17,20 lyase. The substrates used were pregnenolone (P5) for 3 beta-HSD, progesterone (P4) for 17 alpha-hydroxylase, and 17 alpha-hydroxy-progesterone (17 alpha-OH-P4) for 17,20 lyase. The substrates were incubated with the enzyme sources and coenzymes, and the products formed were measured. All the steroids inhibited 3 beta-HSD, and the inhibition by gestrinone (Ki = 3.0 microM) and 3 keto-desogestrel (17.5 microM) was particularly marked. Only desogestrel (Ki = 30.3 microM) and danazol (168 microM) inhibited 17 alpha-hydroxylase. All the steroids inhibited 17,20 lyase, and the inhibition by desogestrel (Ki = 0.70 microM), danazol (0.80 microM), and gestrinone (30 microM) was particularly marked. PMID- 2583059 TI - Regulation of prolactin gene expression during early pregnancy in rats. AB - We have shown that administration of estrogen which increases prolactin (PRL) synthesis in the rat may be mediated by an increase in poly [adenosine diphosphate ribose (ADP-ribose)] synthesis. Present investigation was attempted to study whether poly (ADP-ribose) synthesis is involved in rat PRL gene expression during early pregnancy. Anterior pituitaries were obtained on days 0, 2, 4, 6, 8, 10 and 12 of pregnancy (group C). Another group of pregnant rats was given nicotinamide, an inhibitor of poly (ADP-ribose) synthesis twice a day intra peritoneally from day 0 to the day of sacrifice (group N). Serum estradiol (E2) concentration was determined by radioimmunoassay. PRL mRNA was measured by cytoplasmic dot hybridization using 32P-labeled cDNA. Poly (ADP-ribose) synthesis was assessed by incubating purified nuclei with 14C-nicotinamide adenine dinucleotide. The serum concentration of E2 increased between days 2 and 4, and on day 6 it decreased to the level of day 0. It remained low until day 12. No difference in the serum E2 level was observed in groups C and N. In group C, PRL mRNA increased from day 2 and remained high until day 8. In group C, poly (ADP ribose) synthesis increased between days 2 and 4, decreased on day 6 to the level of day 0, and thereafter gradually increased until day 10. Administration of nicotinamide abolished the increase in poly (ADP-ribose) synthesis observed in group C during early pregnancy. In group N, the increase in PRL mRNA was completely suppressed. It is suggested that the increase in PRL mRNA in early pregnancy may be mediated by increased poly (ADP-ribose) synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583061 TI - Immunoreactive 7B2 concentrations in rats with various endocrine conditions. AB - Changes in 7B2 immunoreactivity in the pituitary as well as in the other brain regions and gut after various endocrine situations were investigated. Gonadectomy and neonatal monosodium glutamate (MSG) treatment resulted in an appreciable increase in the pituitary 7B2 concentration, though 7B2 content in the MSG treated pituitary was not significantly different when calculation was performed on a per pituitary gland basis. The 7B2 concentration in the cerebellum, midbrain and cortex in thyroxine treated rats showed a significant increase, which might indicate possible thyroid hormone involvement in 7B2 metabolism in the brain. The pituitary 7B2 concentration during the estrous cycle did not change significantly. These results suggest that pituitary 7B2 may correlate to the pituitary gonadotropins and that brain 7B2 content may be modulated by thyroid hormones. PMID- 2583060 TI - Calcitonin gene-related peptide in the human hypothalamus. AB - Calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) in the human hypothalamus was investigated by radioimmunoassay and by immunocytochemistry. CGRP-LI was detected from two hypothalami obtained at autopsy (2.1 and 7.0 ng/g wet tissue) by radioimmunoassay. Reverse phase high performance liquid chromatography revealed that most of the CGRP-LI in the human hypothalamus was eluted in an identical position with synthetic human CGRP. For immunocytochemistry, human hypothalami obtained at autopsy were fixed and cryostat-sectioned at 40 microns. Free floating sections were immunostained with antibody to CGRP. CGRP-immunoreactive cell bodies were found in the supraoptic nucleus, paraventricular nucleus and infundibular nucleus. These findings indicate that CGRP exists in the cell bodies of the supraoptic nucleus, paraventricular nucleus and infundibular nucleus in the human hypothalamus and CGRP may play some roles in the endocrine and other functions of the human hypothalamus. PMID- 2583062 TI - Effects of cigarette smoke on norepinephrine turnover and thermogenesis in brown adipose tissue in MSG-induced obese mice. AB - To clarify whether cigarette smoke stimulates the sympathetic nervous system (SNS) and thermogenesis in interscapular brown adipose tissue (IBAT), we measured norepinephrine (NE) turnover, an indicator of SNS activity, guanosine-5' diphosphate (GDP) binding, a thermogenic indicator, and oxygen consumption in IBAT in monosodium-L-glutamate (MSG)-induced obese and saline control mice following a two-week exposure to cigarette smoke. Cigarette smoke significantly increased NE turnover, GDP binding and oxygen consumption in IBAT, and significantly reduced body weight in MSG obese mice as well as in control mice. However, food intake was unchanged in the MSG group. These results suggest that cigarette smoke stimulates NE turnover and thermogenesis in BAT, which contribute to the mitigation of obesity. PMID- 2583063 TI - Neuropeptide Y and blood pressure in haemodialysis patients. AB - To investigate the relationship between plasma neuropeptide Y (NPY) concentrations and blood pressure in haemodialysis (HD), we measured plasma immunoreactive neuropeptide Y (IR-NPY) concentrations and blood pressure before and after HD in 71 patients undergoing maintenance HD. Plasma IR-NPY concentrations were measured by radioimmunoassay after extraction with Sep-Pak C18 cartridges. We corrected the plasma IR-NPY values after HD by reference to the ratio of the plasma total protein levels before HD to the levels after HD, in order to exclude the influence of the haemoconcentration caused by HD. Plasma IR NPY concentrations before and after HD in 71 patients undergoing maintenance HD were 413 +/- 94 pg/ml and 340 +/- 90 pg/ml (mean +/- SD), respectively. Plasma IR NPY concentrations before HD in 28 hypertensive patients with HD (398 +/- 91 pg/ml) were not significantly different from those in 40 normotensive (427 +/- 98 pg/ml) and 3 hypotensive (372 +/- 21 pg/ml) patients with HD (P greater than 0.1). Plasma IR-NPY concentrations after HD in 9 patients whose systolic blood pressure fell more than 30 mmHg during HD (409 +/- 52 pg/ml) were significantly higher than those in the other patients (P less than 0.025). These findings suggest that the release of NPY is increased when the blood pressure falls during HD in patients undergoing maintenance HD. PMID- 2583064 TI - Identification and partial characterization of mesenchyme-derived growth factor that stimulates proliferation and inhibits functional differentiation of mouse mammary epithelium in culture. AB - The effect of mesenchyme on both proliferation and differentiation of mammary epithelial cells was investigated in a primary cell culture system. Mammary cells cultured on collagen gel for 4 days produced casein in response to the synergistic action of insulin, cortisol, and prolactin. When mammary epithelial cells were co-cultured with fibroblasts derived from three different kinds of fetal mesenchymal tissues, casein production was suppressed. The addition of conditioned media obtained from cultures of these mesenchymal cells stimulated DNA synthesis and reduced casein synthesis in a dose-dependent fashion in the cultured mammary cells. Although such biological actions are similar to those of epidermal growth factor (EGF), the capability to compete with EGF for EGF receptor was not found in this conditioned medium. Sephadex G-200 column chromatography revealed that molecular weight of the peak which has these biological activities was around 100,000. These results indicate that fetal mesenchymal cells secrete a substance(s) which has a stimulatory effect on proliferation and an inhibitory effect on differentiation of mammary epithelial cells. PMID- 2583065 TI - Epidermal growth factor (EGF) binding, EGF-dependent autophosphorylation and activity of tyrosine-specific protein kinase in hepatic membrane fractions from fetal, newborn, adult and partially hepatectomized rats. AB - The binding of 125I-epidermal growth factor (EGF) and activities of EGF-receptor autophosphorylation and of tyrosine-specific protein kinases were determined in hepatic membrane fraction from newborn, fetal and hepatectomized adult rats and compared with those of adult control rats. Although the EGF binding was decreased, there was a tendency for the activity of autophosphorylation to be higher and ligand-dependency to be lower in the membranes from growing hepatic tissues. The activity of tyrosine kinases did not differ among animal groups but a supplement of (NH4)2SO4 to the incubation mixture revealed a difference in the EGF-dependency of the activity; the salt inhibited the activity in the control more profoundly than in the newborn and fetus but the activity was partially restored in the presence of EGF, while in the newborn and fetus the activity did not respond to the added EGF. The results suggest that the higher activity with less responsiveness to the ligand of EGF-receptor autophosphorylation and protein tyrosine kinase is one of the characteristics of growing rat hepatic tissues. PMID- 2583066 TI - Suppression of norepinephrine secretion by dopamine in children with neuroblastoma: evidence for precursor inhibition in catecholamine pathway. AB - To elucidate catecholamine (CA) secretory dynamics in neuroblastoma, urinary excretion of CAs and their metabolites was serially measured in 6 patients aged 3 months to 3 years before and during treatment. After tumor extirpation, increased urinary CAs were promptly normalized; the reduction reflected the amount of CA production from the tumor. Urinary dopamine (DA) showed the most prominent reduction, whereas DA content in the tumor was very small, indicating that the DA produced was immediately released from the tumor and metabolized in extra-tumor tissues. In contrast, patients receiving chemotherapy continued to excrete excess DA and homovanillic acid (HVA), which were increased further at recidivation. One patient showed an inverse correlation between DA and norepinephrine (NE) excretion; a decrease in DA was associated with an increase in NE and plasma DA beta-hydroxylase (DBH) activity. A similar inverse correlation was also noted between NE and vanillylmandelic acid (VMA) or 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion, while HVA and dihydroxyphenylacetic acid (DOPAC) were positively correlated with DA excretion. Urinary HVA and VMA were lineally correlated but in a patient excreting an enormous amount of DA, urinary VMA was markedly suppressed in terms of HVA excretion. Excessive DA induced an increase in renal water output but did not enhance Na and K excretion. These results indicate that endogenous DA overload in neuroblastoma inhibits NE production by suppressing DBH activity as well as by forming VMA and MHPG. This precursor regulation appears to be the characteristic of the CA metabolic pathway. PMID- 2583067 TI - Roles of prepubertal androgen, estrogen or androgen plus prolactin on androgen induced proliferative response of seminal vesicles in adult mice. AB - Male mice castrated on day 0 after birth were pretreated daily with testosterone propionate (TP, 4 micrograms/g body weight), 17 beta-estradiol (E2, 0.2 micrograms/g body weight) or vehicle for 21 days starting from day 20. In another experiment, male mice were castrated on day 25; two pituitaries from 60-day-old females were immediately grafted under the capsule of the left kidney in one group. The castrated mice with or without grafts were pretreated daily with TP (4 or 20 micrograms/g body weight) for 36 days starting from day 25, and the left kidney was removed on day 60. Daily TP injections (4 micrograms/g body weight) were started again at 30 days after the end of pretreatments to examine androgen induced proliferation, and incorporation of 5-[125I]iodo-2'-deoxyuridine into the whole seminal vesicles was used as an index of proliferation. In the neonatally castrated mice, both TP and E2 pretreatments given during the prepubertal period significantly increased seminal vesicle weight even long after the end of the pretreatments. However, androgen-induced proliferative response found in the neonatally castrated adult mice (poor response; long duration with a low peak) was changed to that found in mice castrated at adulthood (good response; short duration with a high peak) by the TP pretreatment only but not at all by the E2 pretreatment. In the mice castrated on day 25, a pharmacological dose of TP or TP plus hyperprolactin could not enhance or change the adult castration type of androgen-induced proliferation induced by physiological prepubertal androgens, although both treatments significantly enhanced the prepubertal growth of the seminal vesicles. PMID- 2583068 TI - Environmental cancer risks--real and unreal. PMID- 2583069 TI - Air pollution and acute respiratory morbidity: an observational study of multiple pollutants. AB - Recently there have been several attempts to estimate the health and economic effects of one or more airborne pollutants using the Health Interview Survey (HIS), a large cross-sectional database collected by the National Center for Health Statistics. The ultimate implications of these studies are unclear, however, since they frequently include different pollutants and health outcomes in the regression analysis. This paper attempts to determine the separate health consequences of two air pollutants common to the urban environment, ozone and particulate matter, using six separate years of the HIS. The results, using a fixed effects model that controls for intercity differences, indicate an association between smaller size particles (fine particulate) and both minor restrictions in activity and respiratory conditions severe enough to result in work loss and bed disability in adults. Ozone, on the other hand, appears to be associated only with the more minor restrictions. However, the measurement error associated with estimating exposure to ozone may limit the usefulness of the HIS which relies on a 2-week recall of health status. The results are compared with other studies using the HIS and related studies involving acute respiratory symptoms. PMID- 2583071 TI - Congenital anomalies associated with maternal exposure to oxydemeton-methyl. AB - Thirty-five workers became ill after they entered a cauliflower field contaminated with residues of three different insecticides, the organophosphates oxydemeton-methyl (Metasystox-R) and mevinphos (Phosdrin), and a carbamate, methomyl (Lannate). One crew member was pregnant with a 4-week-old fetus. At birth, the 3200-g female infant had multiple cardiac defects, bilateral optic nerve colobomas, microphthalmia of the left eye, cerebral and cerebellar atrophy, and facial anomalies. The cardiac defects included ventricular and atrial septal defects, stenosis of the pulmonary artery, and a patent ductus arteriosus. The child died at 14 days of age. There was no family history of birth defects, nor any maternal risk factor present, except that doxylamine (Bendectin) had been prescribed at 9 weeks fetal age. It is unlikely that doxylamine was responsible for the observed anomalies. Of the three chemicals involved, reproductive effects in test organisms have been observed only with oxydemeton-methyl. This case represents the first report of human malformations associated with prenatal exposure to this chemical. Further studies may be warranted to determine if a causal relationship exists. PMID- 2583070 TI - Sister chromatid exchange in painters recently exposed to solvents. AB - Epidemiologic studies have suggested that exposure to solvent-based materials in the painting trades is associated with an increased cancer risk. In order to determine if the solvent exposures of current union members of the International Brotherhood of Painters and Allied Tradesman (IBPAT) are associated with a genotoxic risk, we have measured the sister chromatid exchange (SCE) frequency in their peripheral blood lymphocytes. Previous reports have shown that chronic solvent exposure of these workers does not elevate SCE frequencies. We now report that acute exposure, estimated by the number of days worked over the month prior to venipuncture, is associated with elevated SCE levels in currently smoking workers. No elevation in SCE was associated with similar recent exposure in nonsmoking, solvent-exposed painters. PMID- 2583072 TI - Tissue distribution of lead in young common terns: influence of time since exposure. AB - Newly hatched common tern (Sterna hirundo) chicks were injected at 2 days of age with 0.2 mg/g of lead, and subsets were examined at 1, 2, 3, and 20 days postexposure. Control birds (water injection) had low levels (less than 2 ppb) of lead in liver, kidney, muscle, and brain. Lead-dosed chicks 2 days postexposure had liver and kidney residues greater than 1000 ppb (dry weight), and 3-day postexposure chicks showed substantially higher levels. By Day 20 the lead levels had declined by about half. In all samples the liver residue exceeded the kidney level by a factor of 1.5 to 2 in controls and 4.6 to 10.7 in exposed birds. In control birds, only brain and kidney levels were correlated, whereas in exposed birds kidney and liver, and kidney and muscle were correlated as well. PMID- 2583073 TI - Induction of pulmonary metallothionein following oxygen exposure. AB - Metallothionein (MT) levels were measured by radioimmunoassay in lungs of animals exposed 0, 3, and 6 days to 85% oxygen. MT levels increased with duration of exposure from 112.0 ng/lung in sham air control animals to 872.6 ng/lung in animals exposed for 6 days to oxygen. Gel chromatographic analysis of lung homogenates from oxygen-exposed animals revealed the presence of a copper- and zinc-binding component with an approximate molecular weight of 12,000 Da. It was heat stable and cross-reacted with anti-MT. The induction of pulmonary Cu/Zn thionein was accompanied by an acute phase response, characterized by elevated serum Cu and ceruloplasmin levels and depressed serum Zn. Total lung Cu and Zn also increased, perhaps as a consequence of normal repairative processes necessitated by the oxidant injury. Increased adrenal weight and coincident thymic atrophy in oxygen-exposed animals suggested the participation of adrenocorticosteroids in the induction process. PMID- 2583074 TI - In vitro effects of fibrous and nonfibrous silicon nitride on bovine pulmonary macrophages. AB - Bovine pulmonary macrophages were exposed in vitro to 0.3, 0.1, 0.03, or 0.01 mg/ml of a fibrous silicon nitride, nonfibrous (milled) silicon nitride comminuted from the fibrous powder, alpha-quartz (an active control), or glass beads (an inert control). Functional evaluation of the exposed cells indicated that the fibrous silicon nitride was as cytotoxic as quartz, while the nonfibrous silicon nitride was relatively inert. To further evaluate the mechanisms of cytotoxicity, the cells were exposed to 1 mg/ml of the control and test materials and biochemical studies were performed. Quartz increased release of both the cytoplasmic enzyme, lactate dehydrogenase (LDH), and the lysosomal enzyme, acid phosphatase (AP), consistent with both cell membrane and lysosome lysis. In addition, total protein levels were significantly depressed, suggesting significant impairment of cellular synthetic processes. LDH, but not AP, values were increased with fibrous silicon nitride treatment, but not with the nonfibrous silicon nitride. In contrast to quartz, which increased LDH levels by 65%, the fibrous silicon nitride only increased LDH levels by 11%. Scanning electron micrographs further indicated that the fibrous silicon is cytotoxic and poorly tolerated by macrophages. These studies provide further evidence of morphology as a primary determinant of cytotoxicity since the milled powder test article was comminuted from the fibrous material. PMID- 2583075 TI - Pathogenic amoebae in natural thermal waters of three resorts of Hidalgo, Mexico. AB - In a search for free-living amoebae, seven water samples from three thermal water bathing resorts in Tecozautla, Hidalgo, were analyzed during December 1984. The samples were concentrated by filtration and centrifugation, and inoculated later on monoxenic and axenic media. The identification of the isolates was performed by morphology and isoelectric focusing of isoenzymes and total proteins. Thirty three strains of free-living amoebae belonging to the genera Naegleria, Acanthamoeba, and Willaertia were isolated. Twenty of these strains belonged to the Naegleria genus, 16 of them were classified as Naegleria spp., and 2 were classified as Naegleria lovaniensis. Noteworthy was the finding of two pathogenic strains of the species Naegleria australiensis. N. australiensis and N. lovaniensis may be considered good indicator organisms, since they live in the same environmental conditions as N. fowleri, the agent of primary amoebic encephalitis (PAM). On the other hand, amoebae other than Naegleria were isolated and identified as Acathamoeba castellanii (two strains), and Acanthamoeba lugdunensis (one strain), which proved to be pathogenic when tested in mice. Nine more pathogenic strains of the genus Acanthamoeba spp. were isolated together with one strain of Willaertia magna, a thermophilic nonpathogenic amoeba. The chlorination and periodical surveillance of water resorts like the one studied is recommended, in order to prevent the appearance of more cases of PAM or other human diseases associated with pathogenic Acanthamoeba spp. PMID- 2583076 TI - Potential exposure of cooks to airborne mutagens and carcinogens. AB - Recent case-control and proportionate mortality studies in Canada, the United States, Britain, and Denmark have shown that cooks and other food-service workers may have elevated risks of cancers of the nasopharynx, buccal cavity, esophagus, lung, and bladder. The purpose of this pilot study was to determine if there might be airborne products of cooking which may be risk factors for these cancers in cooks. Eight air samples were taken in four restaurants and subsequently analyzed for mutagenicity using the Ames assay, and for carcinogens using gas chromatography/mass spectrometry. All four samples taken in the restaurant cooking areas were mutagenic to TA98 without metabolic activation, and two were mutagenic to TA100 also without metabolic activation. Of the four dining area samples, one was mutagenic to TA100 and one to TA98, both without metabolic activation. Compounds tentatively identified by mass spectrometry did not include known carcinogens. The ventilation systems in all four restaurants allow the exposure of cooks to both the air from dining room smoking areas and the volatile products of cooking. PMID- 2583077 TI - Lung function and chronic exposure to air pollution: a cross-sectional analysis of NHANES II. AB - The effect of air pollution on lung function in children and youths ages 6-24 years was examined, after controlling for age, height, race, sex, body mass, cigarette smoking, and respiratory symptoms. Forced vital capacity (FVC), forced expiratory volume at 1 sec (FEV1), and peak expiratory flow all showed statistically significant (P less than 0.05) negative correlations with annual concentrations of total suspended particulates (TSP), nitrogen dioxide, and ozone. The ozone and NO2 relationships were highly significant. The TSP relationship was less significant. No relationship was found with sulfur dioxide. The relationships held whether or not children with respiratory conditions, or smokers were included. Demographic and geographic variables had little or no impact on the pollution relationships, which also held when only persons still residing in their state of birth were considered. Essentially identical relationships were found using pollution averaged over 2 years. The relationships held across most NO2 concentrations, but were only apparent at high particulate and ozone concentrations. PMID- 2583078 TI - Familial environment associated with type A behaviors and psychophysiological responses to stress in children. AB - This study tested two major hypotheses regarding the characteristics of family environments associated with children's Type A behaviors, anger frequency and expression, hostile outlook, hostility displayed during an interview, and cardiovascular responses to laboratory stressors. Two measures of family environment, Positive Affiliation and Authoritarianism, were derived by a factor analysis of the Family Environment Scale completed by parents. The sample consisted of 66 girls and 48 boys enrolled in Grades 2 through 12 from 114 families residing in a predominantly White, upper-middle-class suburb of Pittsburgh. Analyses largely supported the first hypothesis--that a less supportive and positively involved family climate would be associated with attributes of potential coronary heart disease (CHD) risk in children. Families scoring low on Positive Affiliation had children who were assessed as more angry and hostile on the basis of questionnaires and interview. Boys from these families had a more pronounced heart rate response to all laboratory stressors. The second hypothesis--that authoritarianism, in the absence of positive involvement and supportiveness in the family, would be associated with attributes of potential CHD risk in children--received support in regard to boys' heart rate responses to the serial-subtraction and mirror-image-tracing tasks. High Authoritarianism scores in combination with low Positive Affiliation scores in families predicted a heightened heart rate response in boys. Sex differences in the pattern of associations among family and child characteristics were also found. Results suggest that factors in the family environment may be important influences in children's development of characteristics that may, in adulthood, place them at risk for CHD. PMID- 2583079 TI - Cardiovascular reactivity, mood, and task performance in deprived and nondeprived coffee drinkers. AB - Forty habitual, heavy coffee drinkers (M = 5.7 cups/day) participated in two experimental sessions. Participants were deprived of their morning coffee for one of the laboratory sessions, not deprived the other. During each session, subjects consumed 12 oz of caffeinated coffee, decaffeinated coffee, or caffeine-free herbal tea. Measurements of heart rate, blood pressure, mood, and catecholamine response to deprivation and consumption of the beverage, alone and in combination with challenging tasks, were made. This study found that caffeine continues to cause blood pressure increases with chronic, heavy consumption and that these effects do not appear to habituate with regular use. Subjects reacted to behavioral challenge with fewer negative mood effects if they had consumed caffeine or coffee. Mild caffeine deprivation was associated with symptoms of stress. PMID- 2583081 TI - Trans-situational consistency in smoking relapse. AB - This article explores the question of consistency in ex-smokers' experiences of temptation to smoke. Data were collected from 57 ex-smokers who called a relapse prevention hotline on two occasions. Relapse situations were classified through cluster analysis and were also coded on McKennel's Smoking Motivation factors. Cognitive and behavioral coping efforts were recorded. Only modest trans situational consistency was observed. The two relapse episodes did not systematically fall into the same cluster. Data suggested that social aspects of relapse situations might be most consistent. Behavioral coping showed modest trans-situational consistency, whereas cognitive coping showed no stability. The implications of these findings for the prospect of individually tailored interventions are discussed. PMID- 2583080 TI - Illness representations and matching labels with symptoms. AB - Three studies are reported that show that health-relevant information (e.g., blood pressure [BP] or symptoms) initiates an active cognitive search process that results in the construction of an illness representation. Study 1 showed that informing subjects that their BP was elevated affected two attributes of illness representation: identity (label and symptoms), and time line or expected chronology of the health threat. Subjects given a high-BP reading reported symptoms commonly associated with high BP, especially if they attributed the high BP reading to stress. Study 2 showed that the active search process uses causal information (a third attribute of representations) to give meaning to symptoms. Specifically, subjects used environmental cues to interpret whether familiar, unfamiliar, and ambiguous symptoms were due to illness or to stress. In Study 3 we showed that the constructive process, initiated by a high-BP reading, is directed by prior beliefs about the time line for developing high BP and by the presence of external cues about the stressfulness of the subject's daily life. Subjects who believed BP was labile and that they were under high daily stress or who believed BP was stable and that they were under low daily stress reported more symptoms. The significance of these findings for understanding how people process diagnostic labels and symptom information involved in the construction of illness representations is discussed. PMID- 2583082 TI - Phytochrome activation of two nuclear genes requires cytoplasmic protein synthesis. AB - We have investigated the effects of protein synthesis inhibitors on light-induced expression of two plant nuclear genes, Cab and rbcS, in wheat, pea and transgenic tobacco. Light activation of these two genes is very sensitive to cycloheximide, an inhibitor of cytoplasmic protein synthesis but not to chloramphenicol, an inhibitor of organellar protein synthesis. Studies with chimeric gene constructs in transgenic tobacco seedlings show that cycloheximide exerts its effect at the transcriptional level. As a control, we show that the expression of the cauliflower mosaic virus (CaMV) 35S promoter is enhanced by cycloheximide treatment, irrespective of the coding sequence used. Escape-time analyses with green wheat seedlings show that the cycloheximide block for Cab gene expression is after the primary signal transduction step linked to phytochrome photoconversion. Our results suggest that phytochrome activation of Cab and rbcS is mediated by a labile protein factor(s) synthesized on cytoplasmic ribosomes. PMID- 2583083 TI - The argininosuccinate lyase gene of Chlamydomonas reinhardtii: an important tool for nuclear transformation and for correlating the genetic and molecular maps of the ARG7 locus. AB - The argininosuccinate lyase (ASL) gene of Chlamydomonas reinhardtii has been cloned using four oligonucleotide probes corresponding to highly conserved regions of the ASL polypeptide sequence. The identity of the gene was confirmed by partial sequencing. It is unique, contains several introns and spans a region less than 7.8 kb that includes highly repetitive sequences. Using a particle gun, a reliable nuclear transformation system has been established by complementing three mutants deficient in ASL activity with the wild-type ASL gene. Analysis of the transformants reveals variable patterns of integration of the transforming DNA into the nuclear genome. Previous work has mapped the mutations in the mutants arg2 and arg7 to either end of the ARG7 locus 1.0 to 1.6 recombination map units apart. Our transformation results show that these two mutations are located within a region of 7.8 kb. This allows for the first correlation of the recombination map and the molecular map at the ARG7 locus and indicates a high recombination frequency in this region of the nuclear genome. PMID- 2583084 TI - Two isotocin genes are present in the white sucker Catostomus commersoni both lacking introns in their protein coding regions. AB - Two genes each encoding a distinct precursor protein to the hormone isotocin and a neurophysin-related protein are present in the teleost fish Catostomus commersoni. These precursors are referred to as isotocin 1 and 2. As shown by the polymerase chain reaction technique, both genes lack introns in their protein coding sequences. Both genes are transcribed giving rise to mRNAs of 920 (isotocin 1) and 1020 (isotocin 2) bases, respectively. Based on the nucleotide sequences, the predicted isotocin precursors contain, besides the hormone moiety, a neurophysin-like protein that, in contrast to its mammalian counterpart, is extended at its C-terminus by a peptide which includes a leucine-rich core segment. This segment shows similarities to the copeptin of the mammalian vasopressin precursor that is known to possess prolactin-releasing activity. The data imply that the mammalian copeptin sequence was initially part of a larger ancestral neurophysin molecule. PMID- 2583086 TI - Synthesis and conformational analysis of a series of galactosyl enkephalin analogues showing high analgesic activity. AB - Two galactosyl derivatives of [DMet2,Pro5] enkephalin-amide (compound 1), namely [DMet2,Pro5] enkephalin [N1.5-beta-D-galactopyranosyl] amide (compound 2) and O1.5-(beta-D-galactopyranosyl) [DMet2,Hyp5] enkephalin-amide (compound 3) have been synthesized. Such glycosylpeptides have been shown to be extremely potent analgesic agonists. The conformational analysis of these three compounds in DMSO d6 solution has been carried out using two-dimensional NMR methods. Both the parent compound (1) and the beta N-galactosyl derivative (2) show similar NMR parameters which are consistent with fairly rigid beta-strands at both the N terminus and C-terminus, connected by a glycine residue that displays a mixture between multiple conformational states. Thus, although the beta N-galactosyl derivative (2) has been shown to be significantly more potent than the parent compound (1) in the tail immersion and paw pressure tests of analgesia, no correlation can be established between the conformation of (1) and (2) in DMSO and the difference in analgesic activity. In contrast, important conformational differences with respect to (1) and (2) have been detected in the beta O galactosyl derivative (3). In this case, only one of the likely conformations for (1) and (2) are consistent with the experimental data. These data show that the position of the galactose residue in compound (3) causes Gly3 to loose flexibility leading to a more rigid folded conformation. Such a change in conformation could be related to the difference in analgesic activity between (2) and (3). PMID- 2583085 TI - Proenkephalin A is expressed in mesodermal lineages during organogenesis. AB - Proenkephalin A (PEA) encodes several neuropeptides with an opioid activity, as well as other peptides with as yet unknown functions. As an initial step toward finding possible roles for PEA gene products in non-neuronal tissues, we have determined sites of PEA expression during mouse embryonic development, employing in situ hybridization. We report here the unexpected observation that in addition to its abundance in brain, PEA RNA is expressed in non-differentiated mesodermal cells of diverse lineages in the process of their development into several adult tissues and organs; it drops to undetectable levels upon terminal differentiation of these tissues. In a particular example of differentiating mesoderm, the developing kidney, the transient expression of PEA mRNA and of its encoded peptide Met-enkephalin was demonstrated by both in situ and Northern blot hybridizations, as well as by a radioimmunoassay. These findings suggest a novel role for PEA-derived peptide(s) in mesoderm growth or differentiation during organogenesis. PMID- 2583087 TI - An 18-kd heparin-binding protein of developing brain that is distinct from fibroblast growth factors. AB - An 18-kd heparin-binding protein (p18) was isolated from perinatal rat brain. Although the protein closely resembles the fibroblast growth factors in its strong binding to heparin and in its apparent molecular mass, it has a distinct structure. This was concluded from the amino-terminal sequence analysis that identified a unique structure containing a cluster of lysine residues. Antipeptide antibodies were raised in rabbits according to the sequence analysis and affinity purified using a synthetic peptide. The antibodies were shown to bind specifically to p18, which was immunochemically distinct from the basic fibroblast growth factor. The antipeptide antibodies detected p18 in brain but not in liver, kidney, heart or skeletal muscle. The content of the protein was shown to undergo a remarkable developmental change corresponding to the time period of rapid sprouting of axons and dendrites in brain. The content of p18 was rapidly increased at the time of birth until the postnatal age of approximately 1 week, after which it was decreased to values less than 10% in young adults as compared to the content found in perinatal rats. p18 also enhanced neurite outgrowth in brain neurons in vitro. The protein was stained in neurons in cells dispersed from perinatal brain. The properties of p18 suggest that it has a role in the growth and maturation of brain. PMID- 2583089 TI - Multiple domains of the large fibroblast proteoglycan, versican. AB - The primary structure of a large chondroitin sulfate proteoglycan expressed by human fibroblasts has been determined. Overlapping cDNA clones code for the entire 2389 amino acid long core protein and the 20-residue signal peptide. The sequence predicts a potential hyaluronic acid-binding domain in the amino terminal portion. This domain contains sequences virtually identical to partial peptide sequences from a glial hyaluronate-binding protein. Putative glycosaminoglycan attachment sites are located in the middle of the protein. The carboxy-terminal portion includes two epidermal growth factor (EGF)-like repeats, a lectin-like sequence and a complement regulatory protein-like domain. The same set of binding elements has also been identified in a new class of cell adhesion molecules. Amino- and carboxy-terminal portions of the fibroblast core protein are closely related to the core protein of a large chondroitin sulfate proteoglycan of chondrosarcoma cells. However, the glycosaminoglycan attachment regions in the middle of the core proteins are different and only the fibroblast core protein contains EGF-like repeats. Based on the similarities of its domains with various binding elements of other proteins, we suggest that the large fibroblast proteoglycan, herein referred to as versican, may function in cell recognition, possibly by connecting extracellular matrix components and cell surface glycoproteins. PMID- 2583088 TI - Cytoplasmic domains determine signal specificity, cellular routing characteristics and influence ligand binding of epidermal growth factor and insulin receptors. AB - The cell surface receptors for insulin and epidermal growth factor (EGF) both employ a tyrosine-specific protein kinase activity to fulfil their distinct biological roles. To identify the structural domains responsible for various receptor activities, we have generated chimeric receptor polypeptides consisting of major EGF and insulin receptor structural domains and examined their biochemical properties and cellular signalling activities. The EGF-insulin receptor hybrids are properly synthesized and transported to the cell surface, where they form binding competent structures that are defined by the origin of their extracellular domains. While their ligand binding affinities are altered, we find that these chimeric receptors are fully functional in transmitting signals across the plasma membrane and into the cell. Thus, EGF receptor and insulin receptor cytoplasmic domain signalling capabilities are independent of their new heterotetrameric or monomeric environments respectively. Furthermore, the cytoplasmic domains carry the structural determinants that define kinase specificity, mitogenic and transforming potential, and receptor routing. PMID- 2583090 TI - Genetic basis of the antibody repertoire in Xenopus: analysis of the Vh diversity. AB - The Xenopus IgH locus includes various variable (VH) families, several putative diversity (DH) and at least seven joining (JH) elements, but--although structurally very similar to the mammalian locus--it contributes to a restricted antibody repertoire. The largest three VH families contain 15-30 VH elements which are interspersed at the VHI-VHII and VHII-VHIII boundaries. Twenty-nine genomic and eight expressed VH regions have been sequenced. Each VH family has distinct promoter elements with up to three octamers (ATGCCTAAAT) in either orientation. The incidence of pseudogenes ranges from less than 15% in VHI and VHII to approximately 50% in VHIII, consistent with their relative expression. CDR1 and CDR2 show low overall diversity with nucleotide divergence limited to parts of the CDRs. Randomly selectedly VH elements share CDR1 and CDR2, in some cases also with expressed VH regions. Thus, the complexity of VH elements is not maximal. Patterns of sequence similarities or identities indicate recombination or gene conversion events; sets of direct and inverted repeats flank the sites of, or lie within FR or CDR sequences where these genetic events may occur. Restricted antibody diversity in Xenopus seems therefore to be at least partially related to low complexity of VH elements, frequence of pseudogenes and expression regulated by specific promoter elements; diversity may potentially be increased by (non)homologous recombination events. PMID- 2583092 TI - Transcriptional enhancement by upstream activators is brought about by different molecular mechanisms for class I and II RNA polymerase genes. AB - Ribosomal gene transcription requires the functional interplay of at least two promoter elements, the upstream control element (UCE) and the start site proximal core, which operate in concert to promote efficient and accurate transcription initiation by RNA polymerase I (pol I). Because this bipartite organization of the rDNA promoter is formally analogous to the organization of a typical pol II promoter, we have examined whether transcriptional activation by upstream activating sequences is brought about by similar molecular mechanisms for both classes of genes. We have replaced the UCE of the mouse rDNA promoter by three different pol II activating sequences (the yeast GAL4 binding sites, the target sequence of the enhancer binding protein E2 from bovine papilloma virus type 1 and the octamer motif), and measured the template activity of these chimeric promoters in the presence of the trans-activating proteins either in a cell free transcription system or in vivo after transfection into mouse cells. In the context of the pol I promoter none of these transcriptional activators enhanced rDNA transcription. The results indicate that activation by UCEs is not interchangeable between genes transcribed by RNA pol I and II, respectively, and suggest that different molecular mechanisms mediate the synergistic action of distant control sequences of different classes of genes. PMID- 2583091 TI - Phosphorylation of hepatic phenobarbital-inducible cytochrome P-450. AB - The major phenobarbital-inducible cytochrome P-450 purified from rat liver, a member of family II of the cytochrome P-450 gene superfamily, is rapidly phosphorylated by cAMP-dependent protein kinase. The phosphorylation reaches greater than 0.5 mol phosphate/mol P-450 after 5 min and is accompanied by a decrease in enzyme activity. The serine residue in position 128 was shown to be the sole phosphorylation site and a conformational change of the protein was indicated by a shift of the carbon monoxide difference spectrum of the reduced cytochrome from 450 to 420 nm. Comparison of amino acid sequences of various cytochrome P-450 families revealed a highly conserved arginine residue in the immediate vicinity of the phosphorylated serine residue which constitutes the kinase recognition sequence. It also revealed that only the members of the cytochrome P-450 family II carry this kinase recognition sequence. To find out whether this phosphorylation also occurs in vivo, the exchangeable phosphate pool of intact hepatocytes derived from phenobarbital-pretreated rats was labeled with 32Pi followed by an incubation of the cells with the membrane-permeating dibutyryl-cAMP or with the adenylate cyclase stimulator glucagon to activate endogenous kinase. As a result, a microsomal polypeptide with the same electrophoretic mobility as cytochrome P-450 became strongly labeled. Peptide mapping and immunoprecipitation with monospecific antibodies identified this protein as the major phenobarbital-inducible cytochrome P-450. It becomes phosphorylated at the same serine residues as in the cell-free phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583093 TI - Characterization of Schizosaccharomyces pombe minichromosome deletion derivatives and a functional allocation of their centromere. AB - A 530 kb long Schizosaccharomyces pombe linear minichromosome, Ch16, containing a centric region of chromosome III, has previously been made. In the present study, we constructed a number of deletions in the right and/or left arms of Ch16, and compared their structure and behaviour with Ch16. The functional centromere, cen3, is allocated within a 120 kb long region which is covered by the shortest derivative, Ch10, and is comprised mostly of centromeric repeating sequences. The shortest minichromosome is stable in mitosis and the copy number control is apparently precise. In monosomic meiosis it segregates normally. In disomic meioses, however, the frequency of non-disjunction is very high, suggesting that it may not form a pair. The mitotic loss rate of one of the left-arm deletions, ChR32, which lacks a part of the centromeric repeating sequence, is the highest of all the deletions. This deletion also exhibits the highest precocious sister chromatid separation in meiosis I, suggesting that sister chromatid association might become weakened in ChR32. Our results indicate that the proper meiotic segregation of S.pombe minichromosomes is dependent upon the formation of a bivalent. S.pombe may not have the 'distributive segregation' found with Saccharomyces cerevisiae minichromosomes. PMID- 2583094 TI - The scute (T4) gene acts as a numerator element of the X:a signal that determines the state of activity of sex-lethal in Drosophila. AB - The ratio of X chromosomes to sets of autosomes (X:A) is the primary genetic signal that determines sex and dosage compensation in Drosophila. The gene Sex lethal (Sxl) receives this signal and is responsible for the execution of the alternative developmental programmes of males and females. We have found that the scute (T4) gene, which is involved in neurogenesis, also plays a role in the activation of Sxl. The following results suggest that scute (T4) may be a numerator element of the X:A signal: scute (T4) mutations show female-specific lethality. There are female-specific lethal synergistic interactions between sis a, a previously described numerator element, and mutants for T4. The female lethality is suppressed by SxlM1, a constitutive allele which expresses an active Sxl product independently of the X:A ratio. The Hw685 mutation, which overexpresses T4, is lethal to males with a duplication of sis-a. This lethality is suppressed by either Sxlf1, or the T4 point mutation sc10-1. There are female specific lethal interactions between sc10-1 and daughter-less (da), a gene needed maternally for Sxl to become active. The sc10-1 mutation masculinizes triploid intersexes. PMID- 2583095 TI - Intragenic recombination in a flagellin gene: characterization of the H1-j gene of Salmonella typhi. AB - Salmonella typhi, the etiologic agent of typhoid fever, typically has only a phase-1 flagellar antigen, d, but some isolates, found only in Indonesia, have antigen j instead, and may have a second flagellar antigen, z66. It appears that intragenic recombination involving a directly repeated 11 bp sequence in the H1-d flagellin gene changed the flagellar antigen to j, by deleting 261 bp in its central, antigenically determinant, part. Sequencing of the hypervariable regions of genes H1-d and H1-j, and hybridization of such genes, after amplification by the polymerase chain reaction, with oligonucleotide probes specific for the deleted segment or for the sequence produced by the recombination confirmed that all the j alleles have the postulated deletion. By applying the polymerase chain reaction to study S. typhi isolates from Jakarta, not previously tested in respect to flagellar antigen, we showed that gene H1-j was nearly as common as H1 d in these isolates. PMID- 2583096 TI - Targeting of proteins to the thylakoid lumen by the bipartite transit peptide of the 33 kd oxygen-evolving protein. AB - Various chimeric precursors and deletions of the 33 kd oxygen-evolving protein (OEE1) were constructed to study the mechanism by which chloroplast proteins are imported and targeted to the thylakoid lumen. The native OEE1 precursor was imported into isolated chloroplasts, processed and localized in the thylakoid lumen. Replacement of the OEE1 transit peptide with the transit peptide of the small subunit of ribulose-1,5-bisphosphate carboxylase, a stromal protein, resulted in redirection of mature OEE1 into the stromal compartment of the chloroplast. Utilizing chimeric transit peptides and block deletions we demonstrated that the 85 residue OEE1 transit peptide contains separate signal domains for importing and targeting the thylakoid lumen. The importing domain, which mediates translocation across the two membranes of the chloroplast envelope, is present in the N-terminal 58 amino acids. The thylakoid lumen targeting domain, which mediates translocation across the thylakoid membrane, is located within the C-terminal 27 residues of the OEE1 transit peptide. Chimeric precursors were constructed and used in in vitro import experiments to demonstrate that the OEE1 transit peptide is capable of importing and targeting foreign proteins to the thylakoid lumen. PMID- 2583097 TI - Cytoplasmic intermediate filament proteins of invertebrates are closer to nuclear lamins than are vertebrate intermediate filament proteins; sequence characterization of two muscle proteins of a nematode. AB - The giant body muscle cells of the nematode Ascaris lumbricoides show a complex three dimensional array of intermediate filaments (IFs). They contain two proteins, A (71 kd) and B (63 kd), which we now show are able to form homopolymeric filaments in vitro. The complete amino acid sequence of B and 80% of A have been determined. A and B are two homologous proteins with a 55% sequence identity over the rod and tail domains. Sequence comparisons with the only other invertebrate IF protein currently known (Helix pomatia) and with vertebrate IF proteins show that along the coiled-coil rod domain, sequence principles rather than actual sequences are conserved in evolution. Noticeable exceptions are the consensus sequences at the ends of the rod, which probably play a direct role in IF assembly. Like the Helix IF protein the nematode proteins have six extra heptads in the coil 1b segment. These are characteristic of nuclear lamins from vertebrates and invertebrates and are not found in vertebrate IF proteins. Unexpectedly the enhanced homology between lamins and invertebrate IF proteins continues in the tail domains, which in vertebrate IF proteins totally diverge. The sequence alignment necessitates the introduction of a 15 residue deletion in the tail domain of all three invertebrate IF proteins. Its location coincides with the position of the karyophilic signal sequence, which dictates nuclear entry of the lamins. The results provide the first molecular support for the speculation that nuclear lamins and cytoplasmic IF proteins arose in eukaryotic evolution from a common lamin-like predecessor. PMID- 2583098 TI - Excision products of the T cell receptor gene support a progressive rearrangement model of the alpha/delta locus. AB - We have cloned extrachromosomal circular DNAs containing T cell receptor (TCR) delta gene segments in adult mouse thymocytes and splenocytes. We find that the frequency of circular DNA clones carrying germline delta sequences is lower than that of J alpha probe-positive clones, possibly related to increasing 5' distance from the most upstream J alpha segment. This suggests that the TCR alpha/delta locus is successively rearranged from within and that the delta-containing excision products are progressively diluted out by the subsequent cell division which includes further alpha gene rearrangements. In addition, examination of delta gene excision products revealed newly identified V delta subfamilies, the reciprocal joining of two D delta elements, J delta 2 usage in thymocytes and novel sequences homologous to the human delta-gene deleting elements. PMID- 2583099 TI - Facultative polypeptide translocation allows a single mRNA to encode the secreted and cytosolic forms of plasminogen activators inhibitor 2. AB - Two forms of plasminogen activators inhibitor 2 (PAI-2) are synthesized by human and murine monocytes/macrophages: one accumulates in the cytosol, while the other is translocated into the endoplasmic reticulum, glycosylated and secreted. We show here that a single mRNA encodes both forms of PAI-2. Firstly, a single PIA-2 mRNA was detected by Northern blot hybridization and by RNase protection. Secondly, transfection of a PAI-2 cDNA led to the synthesis of both forms of PAI 2. Finally, in vitro translation of an mRNA transcript of the PAI-2 cDNA in the presence of microsomal membranes generated two topologically distinct forms of PAI-2. The cytosolic and secreted forms of PAI-2 do not result from the use of two translation start sites, since their synthesis initiates at the same AUG, in a sequence context that is conserved between the human and murine genes. Thus, the accumulation of one polypeptide into two topologically distinct cellular compartments can be achieved by facultative translocation. PMID- 2583101 TI - Head activator acts as an autocrine growth factor for NH15-CA2 cells in the G2/mitosis transition. AB - The neuropeptide head activator (HA) acts as an autocrine growth factor for the neural cell line NH15-CA2. Cell proliferation is increased in the presence of HA and inhibited by HA peptide-specific antisera. Stimulation of cellular proliferation is visible 2 h after HA application as an increase in cells in mitosis. HA has no direct effect on stimulating DNA synthesis. HA thus functions as a control signal in the G2/mitosis transition and not in the G1/S transition. Receptors for HA are present on small round cells in clusters of foci and not on cells with differentiated morphology, suggesting cell-cycle-dependent HA receptor expression. PMID- 2583100 TI - Intermolecular transphosphorylation between insulin receptors and EGF-insulin receptor chimerae. AB - The insulin receptor, a glycoprotein consisting of two extracellular alpha- and two transmembrane beta-subunits, is thought to mediate hormone action by means of its tyrosine-specific protein kinase activity. To explore the mechanism of insulin receptor phosphorylation we have used NIH3T3 cells transfected with two receptor constructs: one encoding a chimeric receptor composed of the extracellular domain of the human EGF receptor and the cytosolic domain of the human insulin receptor beta-subunit, and a second construct encoding a kinase defiecient human insulin receptor. Stimulation of these cells with EGF induced tyrosine autophosphorylation of the EGF-insulin receptor chimera (150 kd) and tyrosine phosphorylation of the beta-subunit of the kinase-deficient insulin receptor (95 kd). The phosphopeptides of the autophosphorylated cytoplasmic domain of the EGF-insulin receptor chimera were comparable to those of the transphosphorylated beta-subunit of the kinase-deficient insulin receptor and of the wild-type human insulin receptor. When immunoaffinity purified EGF-insulin receptor hybrids and kinase-deficient insulin receptors were used in a cell lysate phosphorylation assay, it was found that addition of EGF produced 32P labeling of both receptor species. We conclude that EGF acting directly through the EGF-insulin receptor chimera causes transphosphorylation of the kinase deficient insulin receptor. These data support the notion that autophosphorylation of the insulin receptor may proceed by an intermolecular mechanism. PMID- 2583102 TI - Suppression of MHC class I gene expression by N-myc through enhancer inactivation. AB - Amplification of the N-myc oncogene in human neuroblastoma is associated with increased metastatic ability. We previously found that over-expression of N-myc in rat neuroblastoma tumor cells causes a dramatic reduction in the expression of MHC class I mRNA. We show here that two distinct elements in the promoter render the MHC class I genes susceptible to N-myc-mediated suppression, one of which was identified as the MHC class I gene enhancer. Our data indicate that elevated N myc expression is associated with reduced binding of a transcription factor that activates this enhancer. As a result, the activity of the MHC class I gene enhancer is greatly diminished. Elevated expression of the N-myc oncogene in human neuroblastomas and murine pre-B lymphoid lines also correlated with reduced factor binding to the MHC class I gene enhancer. Thus, an important effect of N myc may be to impair the function of certain cellular enhancers by altering the levels of their cognate binding proteins. PMID- 2583105 TI - Proper expression of myosin genes in transgenic nematodes. AB - Caenorhabditis elegans has four genes which encode skeletal myosin heavy chain isoforms. We have re-introduced clones of two of these genes, myo-3 and unc-54 at low copy number into the germline of C. elegans. The resulting loci behave as functional copies of the genes by two genetic criteria: (i) they can result in phenotypic rescue of strains carrying inactivating myo-3 or unc-54 mutations, and (ii) their presence in strains with wild-type copies of the endogenous myosin loci has genetic consequences similar to duplicating the endogenous loci. The re introduced genes function at a level close to that of the endogenous loci. Monoclonal antibodies specific for the different isoforms have been used to localize the expressed proteins. The re-introduced genes express in precisely the same cell types as the endogenous genes, and the myosin products produced assemble into filament structures as in wild-type. Unexpectedly, we have found in the course of this work that very high copy numbers of the unc-54 gene lead to a disruption of muscle structure which may result from overexpression of the protein product. PMID- 2583103 TI - Characterization of the RNA polymerases of Trypanosoma brucei: trypanosomal mRNAs are composed of transcripts derived from both RNA polymerase II and III. AB - To analyze transcription in Typanosoma brucei, we have characterized the trypanosomal RNA polymerases. Here we present our results, which allow a discrimination between the different classes of RNA polymerases in nuclear run-on experiments by polymerase inhibitors and Mn2+ dependence. We also describe the separation of trypanosomal RNA polymerases by chromatography, demonstrating that T. brucei contains RNA polymerases I-III. The outcome of our experiments suggests that the VSG genes of T. brucei are not transcribed by RNA polymerase I, as previously reported, but by RNA polymerase II. We propose that an additional factor modifies RNA polymerase II, resulting in the alpha-amanitin-resistant transcription of VSG genes. Our data also suggest that the mini-exon genes, which encode the 5' end of each trypanosomal mRNA, are probably transcribed by RNA polymerase III. PMID- 2583104 TI - Autoregulation of RNase III operon by mRNA processing. AB - RNase III has been implicated in the control of gene expression by the processing of mRNA. We have found that the rnc operon is autoregulated; rnc- mutant strains oversynthesize the operon's mRNA and protein products. A site in the 5'-noncoding region of the operon's message is cleaved by RNase III. This site-specific cleavage appears to be the initial step in the functional inactivation of the message, since the half-life of the cut message is dramatically shorter than that of the uncut message. PMID- 2583106 TI - The minor myosin heavy chain, mhcA, of Caenorhabditis elegans is necessary for the initiation of thick filament assembly. AB - Caenorhabditis elegans body wall muscle has two distinct myosin heavy chain isoforms, mhcA and mhcB. Mutations eliminating the major isoform, mhcB, have previously been shown to yield paralyzed, viable animals. In this paper we show that the minor isoform, mhcA, is essential for viability. We have utilized the known physical map position of the gene encoding mhcA to obtain two recessive lethal mutations that virtually eliminate accumulation of mhcA. The mutations are allelic, and the interactions of these alleles with mutations affecting other thick filament components are consistent with the hypothesis that the new mutations lie in the structural gene for mhcA. The homozygous mutant animals move very little and morphological analysis shows that thick filament assembly is severely impaired. Together with the location of mhcA in the center of the thick filament (Miller et al., 1983), the results suggest that mhcA has a unique role in initiating filament assembly. The homozygous mutations have an unexpected effect on morphogenesis that indicates an interaction between the muscle cells and the hypodermis during development. The resultant phenotype may be useful in the search for additional essential muscle genes. PMID- 2583107 TI - Drosophila Sgs3 TATA: effects of point mutations on expression in vivo and protein binding in vitro with staged nuclear extracts. AB - The Drosophila salivary gland secretion protein gene, Sgs3, has a consensus TATA sequence and gives rise to abundant stage and tissue-specific transcripts. Two TATA point mutations (TAAA and TAGA) reduce transcript levels approximately 50 fold when assayed in transgenic flies. This effect is reflected in vitro, in DNase I footprint and gel retardation assays where we observed TATA-probe specific complexes that are not seen with TAAA, TAGA or non-specific probes. The binding patterns observed when using nuclear extracts from 0-2- and 0-20-h embryos (Sgs3 inactive) differ from those seen with extracts from third instar salivary glands (Sgs3 active). There are also differences in in vitro binding when using an hsp70 TATA fragment, previously shown to substitute in vivo for the Sgs3 TATA sequence, as probe. Together these observations suggest the possibility that more than one TATA box factor may be present in these extracts. We conclude that a wild-type TATA motif is crucial for the binding of a TATA box factor and all subsequent interactions with other factors bound to the proximal and distal regulatory sequences that are necessary for the normal expression of Sgs3. PMID- 2583108 TI - The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. AB - A stoichiometric complex formed between human alpha-thrombin and D-Phe-Pro-Arg chloromethylketone was crystallized in an orthorhombic crystal form. Orientation and position of a starting model derived from homologous modelling were determined by Patterson search methods. The thrombin model was completed in a cyclic modelling-crystallographic refinement procedure to a final R-value of 0.171 for X-ray data to 1.92 A. The structure is in full agreement with published cDNA sequence data. The A-chain, ordered only in its central part, is positioned along the molecular surface opposite to the active site. The B-chain exhibits the characteristic polypeptide fold of trypsin-like proteinases. Several extended insertions form, however, large protuberances; most important for interaction with macromolecular substrates is the characteristic thrombin loop around Tyr60A Pro60B-Pro60C-Trp60D (chymotrypsinogen numbering) and the enlarged loop around the unique Trp148. The former considerably restricts the active site cleft and seems likely to be responsible for poor binding of most natural proteinase inhibitors to thrombin. The exceptional specificity of D-Phe-Pro-Arg chloromethylketone can be explained by a hydrophobic cage formed by Ile174, Trp215, Leu99, His57, Tyr60A and Trp60D. The narrow active site cleft, with a more polar base and hydrophobic rims, extends towards the arginine-rich surface of loop Lys70-Glu80 that probably represents part of the anionic binding region for hirudin and fibrinogen. PMID- 2583109 TI - Adenovirus polypeptide IX revealed as capsid cement by difference images from electron microscopy and crystallography. AB - Particles of adenovirus type 2 (ad2), when disassembled, consistently yield groups-of-nine (GON) hexons, which are the major virion shell component. The location of a minor component (6%) of the GON has been determined using a novel combination of electron microscopy and X-ray crystallography. The Brookhaven Scanning Transmission Electron Microscope (STEM) was used to estimate the distribution of protein in the GON to a resolution of 15-18 A. The relative hexon positions then were determined to within 1 A using a model of the hexon derived from the X-ray crystal structure to search the STEM image. The difference image between the STEM image and a model hexon group reveals individual monomers of polypeptide IX extending along the hexon--hexon interfaces. The distribution confirms our earlier proposal that four trimers of polypeptide IX are embedded in the large cavities in the upper surface of the GON to cement hexons into a highly stable assembly. PMID- 2583110 TI - Multiple zones in the sequence of calreticulin (CRP55, calregulin, HACBP), a major calcium binding ER/SR protein. AB - The complete amino acid sequence of CRP55, the major 55 kd calcium binding protein of the ER lumen, was deduced from the murine cDNA nucleotide sequence. This was completed using a novel application of PCR amplification. The mature 399 residue protein encoded is preceded by a 17 amino acid leader sequence and ends in the ER signal sequence, KDEL. The protein contains no calcium binding motifs of the EF hand type or of the form seen in calelectrin-related proteins. The major region of potential low affinity calcium binding sites is a polyacidic stretch towards the C terminus. The primary structure of the protein is markedly zonal. The N-terminal region, of approximately neutral net charge and hydrophobicity, is followed by a central proline-rich zone with repeat sequences separated from the polyacidic C-terminal stretch by a short hydrophobic sequence. The general shape suggested is a globular domain attached to an extended tail. Immunofluorescence studies show that the protein is present in skeletal muscle and indicate that it is a sarcoplasmic reticulum protein. We propose that the protein be named calreticulin to reflect its calcium binding activity and location in the ER and SR. PMID- 2583111 TI - Differential expression of myogenic determination genes in muscle cells: possible autoactivation by the Myf gene products. AB - The development of muscle cells involves the action of myogenic determination factors. In this report, we show that human skeletal muscle tissue contains, besides the previously described Myf-5, two additional factors Myf-3 and Myf-4 which represent the human homologues of the rodent proteins MyoD1 and myogenin. The genes encoding Myf-3, Myf-4 and Myf-5 are located on human chromosomes 11, 1, and 12 respectively. Constitutive expression of a single factor is sufficient to convert mouse C3H 10T1/2 fibroblasts to phenotypically normal muscle cells. The myogenic conversion of 10T1/2 fibroblasts results in the activation of the endogenous MyoD1 and Myf-4 (myogenin) genes. This observation suggests that the expression of Myf proteins leads to positive autoregulation of the members of the Myf gene family. Individual myogenic colonies derived from MCA C115 cells (10T1/2 fibroblast transformed by methylcholanthrene) express various levels of endogenous MyoD1 mRNA ranging from nearly zero to high levels. The Myf-5 gene was generally not activated in 10T1/2 derived myogenic cell lines but was expressed in some MCA myoblasts. In primary human muscle cells Myf-3 and Myf-4 mRNA but very little Myf-5 mRNA is expressed. In mouse C2 and P2 muscle cell lines MyoD1 is abundantly synthesized together with myogenin. In contrast, the rat muscle lines L8 and L6 and the mouse BC3H1 cells express primarily myogenin and low levels of Myf-5 but no MyoD1. Myf-4 (myogenin) mRNA is present in all muscle cell lines at the onset of differentiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583113 TI - Lysosomal acid phosphatase is transported to lysosomes via the cell surface. AB - Lysosomal acid phosphatase (LAP) is transported as a transmembrane protein to dense lysosomes. The pathway of LAP to lysosomes includes the passage through the plasma membrane. LAP is transported from the trans-Golgi to the cell surface with a half-time of less than 10 min. Cell surface LAP is rapidly internalized. Most of the internalized LAP is transported back to the cell surface. On average, each LAP molecule cycles greater than 15 times between the cell surface and the endosomes before it is transferred to dense lysosomes. At equilibrium approximately 4 times more LAP precursor is present in endosomes than at the cell surface. Exposing cells to reduced temperature or weak bases such as NH4Cl, chloroquine and primaquine decreases the steady-state concentration of LAP at the cell surface. The recycling pathway is operative at greater than or equal to 20 degrees C and does not include passage of the Golgi/trans-Golgi network. LAP is transferred with a half-time of 5-6 h from the plasma membrane/endosome pool to dense lysosomes, from where it does not recycle to the endosome/plasma membrane pool at a measurable rate. PMID- 2583112 TI - Differential brain expression of the Alzheimer's amyloid precursor protein. AB - The expression of the Alzheimer amyloid protein precursor (AAPP) was examined in human, monkey, dog and rat brains. Two proteins, one identified as AAPP695 and the other as AAPP751, were immunoprecipitated from the in vitro translation of human, dog and rat brain polysomes. The AAPP751 to AAPP695 ratio was highest in human, intermediate in dog and lowest in rat brain polysomes. Human cerebral cortex contained higher levels of the AAPP751 mRNA than either dog or rat cortex. AAPP695 was detected in both cerebral cortex and cerebellum of all species examined. In contrast, AAPP751 was detected predominantly in the cortex of human, monkey and to a lesser extent dog brains while it was not detected in rat brain. These findings indicate that the amyloid precursors are differentially expressed in different mammalian brains and suggest that AAPP751 is mainly expressed in the brain regions involved in plaque formation. PMID- 2583114 TI - Internalization and recycling of CD4 transfected into HeLa and NIH3T3 cells. AB - The internalization of CD4, a T cell differentiation antigen and the receptor for the human immunodeficiency viruses (HIV-1 and -2), has been examined in HeLa and murine 3T3 cells transfected with CD4 cDNA. Fab' fragments of the anti-CD4 monoclonal antibody Leu3a were generated by pepsin digestion and used as a specific monovalent, non-crosslinking ligand for CD4. These Fab' fragments were shown to bind to CD4 on the transfected cells with an affinity similar to that of HIV gp120, and inhibited HIV infection of lymphocytic cells. The Fab' fragments were radioiodinated and used in an acid-stripping endocytosis assay to demonstrate that the CD4 expressed on transfected HeLa and NIH3T3 cells was internalized. Approximately 1.5-2% of the total cell-bound [125I]Fab' fragments were internalized per minute. Furthermore, the internalized [125I]Fab' fragments could be shown to recycle to the cell surface. After 30-60 min a steady state was reached between internalization and recycling, with approximately 30-40% of the total cellular CD4 pool residing inside the cell. Similar results were obtained in studies with the intact divalent radiolabelled Leu3a antibody. These data demonstrate that CD4 expressed on transfected non-lymphoid cells is constitutively endocytosed and recycled. PMID- 2583115 TI - Role of the zeta chain in the expression of the T cell antigen receptor: genetic reconstitution studies. AB - The zeta (zeta) chain plays a central role in T cell antigen receptor assembly and signal transduction. From previous work in murine T cell hybridomas we have inferred that the zeta subunit is limiting in receptor assembly. Partial receptors made in excess of zeta are assembled in the endoplasmic reticulum, transported through the Golgi, but then rapidly and efficiently degraded in lysosomes. zeta would therefore seem to play a unique role in targeting receptors from the Golgi to the cell surface. To determine directly whether zeta limits receptor assembly we have reconstituted a zeta-deficient T cell line by transfection of the murine zeta cDNA. Transfection results in restoration of expression of surface T cell receptor. In addition, increasing zeta expression results in a commensurate increase in the survival of previously excess subunits. This is reflected in an increased surface expression of complete receptors. Finally, transfection of the zeta cDNA fails to produce detectable zeta-eta heterodimers. The implications of these findings with regard to receptor assembly, and the relationship between zeta and eta, are discussed. PMID- 2583117 TI - A physical map linking the five CD1 human thymocyte differentiation antigen genes. AB - Human CD1 is a family of thymocyte differentiation antigens which consist of heavy chains with mol. wts between 43 and 49 kd binding to beta 2 microglobulin. They are distant relatives of the major histocompatibility complex (MHC) class I and II products. Five human CD1 genes have been described. Three (CD1A, -B and C) code for the serologically defined CD1a, -b and -c antigens. The protein products of the other two genes, CD1D and CD1E, remain unknown. All CD1 genes are located on chromosome 1 and hence are independent of the MHC locus. In this paper, the tight linkage of the CD1 genes has been established by pulse field gel electrophoresis, cosmid cloning and walking techniques. The 190 kb of DNA linking all five CD1 genes has been spanned by 14 overlapping cosmids. The order of the genes in the CD1 complex is CD1D-CD1A-CD1C-CD1B-CD1E, and, with the exception of CD1B, they are arranged in the same transcriptional orientation. The genes are evenly spaced in the complex except for the distance between CD1D and CD1A, which is two to three times greater than the average. PMID- 2583116 TI - Iron regulation of transferrin receptor mRNA levels requires iron-responsive elements and a rapid turnover determinant in the 3' untranslated region of the mRNA. AB - Post-transcriptional regulation of transferrin receptor mRNA levels by iron is mediated by a portion of the 3' untranslated region (UTR) of the mRNA. We have previously shown that a 678 nucleotide fragment of the 3'UTR contains the regulatory element(s). Within this region are five RNA structures which resemble the iron-responsive element (IRE) in the 5' untranslated region of the ferritin mRNA which is regulated translationally by iron. The IREs from the ferritin and transferrin receptor mRNAs compete in an in vitro assay for interaction with a cytoplasmic protein; the activity of this IRE-binding protein is dependent upon the iron status of the cells. Based on further deletion analysis reported here, the sequence required for iron regulation of the transferrin receptor have been limited to 250 nucleotides which we have produced synthetically and cloned. This sequence, which contains three IREs, is capable of producing iron-dependent regulation of transferrin receptor levels. Removal of the three IREs from the synthetic element results in loss of iron regulation. Moreover, deletion of a single cytosine residue from each of the three IREs in the synthetic regulatory element eliminates high-affinity binding to the IRE-binding protein in vitro and results in low levels of iron-independent transferrin receptor expression, consistent with production of a constitutively unstable mRNA. These data indicate that the ability of the mRNA to interact with the IRE-binding protein is required for regulation of transferrin receptor mRNA levels by iron.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583119 TI - A U-snRNA gene-specific upstream element and a -30 'TATA box' are required for transcription of the U2 snRNA gene of Arabidopsis thaliana. AB - The U2 and U5 snRNA genes of Arabidopsis thaliana contain in their promoter regions two elements with conserved sequence and position. To test the significance of this conservation we have made a construction in which the promoter of the U2 RNA gene is replaced by the synthetic 98 bp long sequence containing the two conserved elements: an upstream sequence element, GTCCCACATCG (USE, pos. -78 to -68), and a TATA-like sequence TATAAATA (-33 to -26), positioned approximately three helical turns apart, as in the wild-type promoter. This synthetic promoter efficiently drove transcription of the U2 gene in transfected protoplasts of Nicotiana plumbaginifolia. The importance of the individual elements and of their position within the promoter was investigated. Deletion of the USE, change of its orientation, and some single point mutations all decreased transcription 10- to 20-fold, and replacement of the TATA-like element by an unrelated sequence inactivated the promoter. Mutants in which the spacing between the USE and TATAAATA was changed were less active but no correlation was observed between promoter activity and insertion of either odd or even numbers of half helical turns. Insertion of a spacer between TATAAATA and the cap site resulted in accumulation of U2 RNA with an extended 5' end, indicating that the TATAAATA element is responsible for selection of the initiation site. The data indicate that the promoters of RNA polymerase II specific U-snRNA genes in higher plants differ from their animal counter-parts and also from plant mRNA gene promoters. They contain two essential elements, an USE, an element found only in U-snRNA genes, and a TATA element which is indistinguishable from the TATA boxes of mRNA-coding genes. PMID- 2583118 TI - Cooperative binding of estrogen receptor to imperfect estrogen-responsive DNA elements correlates with their synergistic hormone-dependent enhancer activity. AB - The Xenopus vitellogenin (vit) gene B1 estrogen-inducible enhancer is formed by two closely adjacent 13 bp imperfect palindromic estrogen-responsive elements (EREs), i.e. ERE-2 and ERE-1, having one and two base substitutions respectively, when compared to the perfect palindromic consensus ERE (GGTCANNNTGACC). Gene transfer experiments indicate that these degenerated elements, on their own, have a low or no regulatory capacity at all, but in vivo act together synergistically to confer high receptor- and hormone-dependent transcription activation to the heterologous HSV thymidine kinase promoter. Thus, the DNA region upstream of the vitB1 gene comprising these two imperfect EREs separated by 7 bp, was called the vitB1 estrogen-responsive unit (vitB1 ERU). Using in vitro protein-DNA interaction techniques, we demonstrate that estrogen receptor dimers bind cooperatively to the imperfect EREs of the vitB1 ERU. Binding of a first receptor dimer to the more conserved ERE-2 increases approximately 4- to 8-fold the binding affinity of the receptor to the adjacent less conserved ERE-1. Thus, we suggest that the observed synergistic estrogen-dependent transcription activation conferred by the pair of hormone-responsive DNA elements of the vit B1 ERU is the result of cooperative binding of two estrogen receptor dimers to these two adjacent imperfect EREs. PMID- 2583120 TI - Binding of the 3' terminus of tRNA to 23S rRNA in the ribosomal exit site actively promotes translocation. AB - A key event in ribosomal protein synthesis is the translocation of deacylated tRNA, peptidyl tRNA and mRNA, which is catalyzed by elongation factor G (EF-G) and requires GTP. To address the molecular mechanism of the reaction we have studied the functional role of a tRNA exit site (E site) for tRNA release during translocation. We show that modifications of the 3' end of tRNAPhe, which considerably decrease the affinity of E-site binding, lower the translocation rate up to 40-fold. Furthermore, 3'-end modifications lower or abolish the stimulation by P site-bound tRNA of the GTPase activity of EF-G on the ribosome. The results suggest that a hydrogen-bonding interaction of the 3'-terminal adenine of the leaving tRNA in the E site, most likely base-pairing with 23S rRNA, is essential for the translocation reaction. Furthermore, this interaction stimulates the GTP hydrolyzing activity of EF-G on the ribosome. We propose the following molecular model of translocation: after the binding of EF-G.GTP, the P site-bound tRNA, by a movement of the 3'-terminal single-stranded ACCA tail, establishes an interaction with 23S rRNA in the adjacent E site, thereby initiating the tRNA transfer from the P site to the E site and promoting GTP hydrolysis. The co-operative interaction between the E site and the EF-G binding site, which are distantly located on the 50S ribosomal subunit, is probably mediated by a conformational change of 23S rRNA. PMID- 2583121 TI - Correlation of the expression of the nuclear photosynthetic gene ST-LS1 with the presence of chloroplasts. AB - A detailed analysis of the expression of a chimeric gene, consisting of the upstream region of the nuclear photosynthetic gene ST-LS1, encoding a component of the water-oxidizing complex of photosystem II, fused to the coding sequence of beta-glucuronidase (GUS) as a reporter, is described. The expression of this chimeric gene at the cellular level was detected by histochemical methods and shows that the expression of this gene is correlated with the presence of chloroplasts. Interestingly, the GUS activity was not only detected in typical photosynthetic tissues, e.g. leaves and stems, but also in green roots containing chloroplasts. In contrast no activity was detected in neighbouring white root tissue which was devoid of chloroplasts. One can therefore separate the relative importance of the (morphological) differentiation steps responsible for the formation of tissues normally involved in photosynthesis, from the importance of the developmental stage (characterized by the presence of chloroplasts), for the expression of this nuclear photosynthetic gene. Our data strongly suggest that the developmental stage of the plastids is the primary determinant for the activity of this nuclear photosynthetic gene, although they do not yet allow the exclusion of the reverse type of control, i.e. control of the differentiation of the plastid by the expression of certain nuclear genes. A chimeric gene, consisting of the promoter of the 35S cauliflower mosaic virus (CaMV) gene and the GUS coding sequence, was used as a control throughout the experiments, confirming that the observed differential ST-LS1-GUS gene expression reflects the particular transcriptional regulation impacted on this gene by its cis-acting regulatory sequences. PMID- 2583122 TI - An enhancer located in a CpG-island 3' to the TCR/CD3-epsilon gene confers T lymphocyte-specificity to its promoter. AB - The gene encoding the CD3-epsilon chain of the T cell receptor (TCR/CD3) complex is uniquely transcribed in all T lymphocyte lineage cells. The human CD3-epsilon gene, when introduced into the mouse germ line, was expressed in correct tissue specific fashion. The gene was then screened for T lymphocyte-specific cis-acting elements in transient chloramphenicol transferase assays. The promoter (-228 to +100) functioned irrespective of cell type. A 1225 bp enhancer with strict T cell specificity was found in a DNase I hypersensitive site downstream of the last exon, 12 kb from the promoter. This site was present in T cells only. The CD3 epsilon enhancer did not display sequence similarity with the T cell-specific enhancer of CD3-delta, a related gene co-regulated with CD3-epsilon during intrathymic differentiation. The CD3-epsilon enhancer was unusual in that it constituted a CpG island, and was hypomethylated independent of tissue type. Two HTLV I-transformed T cell lines were identified in which the CD3-epsilon gene was not expressed, and in which the enhancer was inactive. PMID- 2583123 TI - A thyroid-specific nuclear protein essential for tissue-specific expression of the thyroglobulin promoter. AB - A rat thyroglobulin promoter fragment, capable of directing thyroid-specific transcription, binds at least three different factors, TTF-1, TTF-2 and UFA, which are all present in nuclear extracts of the differentiated rat thyroid cell line FRTL-5. TTF-1 and TTF-2 are FRTL-5 specific, as demonstrated by their absence in nuclear extracts prepared from cell lines that do not express any thyroid-differentiated function, while UFA is present in all cell lines tested. TTF-1 has been extensively purified. It binds to the rat thyroglobulin promoter at three different sites which share sequence homology. Mutations in two of the three sites decrease both binding of TTF-1 in vitro and promoter function in vivo. This suggests that the tissue-specific expression of the thyroglobulin genes is mediated, at least in part, by the presence of a transcription factor exclusively in thyroid cells. PMID- 2583124 TI - Mouse interleukin-2 structure-function studies: substitutions in the first alpha helix can specifically inactivate p70 receptor binding and mutations in the fifth alpha-helix can specifically inactivate p55 receptor binding. AB - The function of two alpha-helical regions of mouse interleukin-2 were analyzed by saturation substitution analysis. The functional parts of the first alpha-helix (A) was defined as residues 31-39 by the observation that proline substitutions within this region inactivate the protein. Four residues within alpha-helix A, Leu31, Asp34, Leu35 and Leu38, were found to be crucial for biological activity. Structural modeling suggested that these four residues are clustered on one face of alpha-helix A. Residues 31 and 35 had to remain hydrophobic for the molecule to be functional. At residue 38 there was a preference for hydrophobic side chain residues, while at residue 34 some small side chain residues as well as acidic or amide side chain residues were functionally acceptable. Inactivating changes at residue 34 had no effect upon the ability of the protein to interact with the p55 receptor. Disruption of the fifth alpha-helix (E), which had little effect upon biological activity, resulted in an inability of the protein to interact with the p55 receptor. Mutagenesis of the alpha-helix E region demonstrated that alpha helicity and the nature of the side chain residues in this region were unimportant for biological activity. The region immediately proximal to alpha helix E was important only for the single intramolecular disulfide linkage. PMID- 2583125 TI - A stable alpha-helical element in the carboxy-terminal domain of free and chromatin-bound histone H1 from sea urchin sperm. AB - The carboxy-terminal domain (residues 121-248) of sea urchin sperm-specific H1 is not random coil but partly alpha-helical, even in 1 mM sodium phosphate, pH 7. The helix resides in a 57 residue proline-free segment which, in the intact histone, immediately abuts the central globular domain. The proline-free region, which is rich in lysine and alanine, is relatively resistant to tryptic digestion when the carboxy-terminal domain is bound to DNA. Two (overlapping) resistant peptides are shown by circular dichroism measurements to be substantially alpha helical in 1 mM sodium phosphate and to increase in helix content to approximately 70% in 1 M NaCLO4. Tryptic digestion of chromatin gives resistant fragments containing both the globular domain and the contiguous proline-free segment, strongly suggesting that the alpha-helical segment also exists in chromatin, where it would be ideally placed to direct the path of the linker DNA entering or leaving the nucleosome. The linker in sea urchin sperm chromatin is long (approximately 74 bp), and the unusually long alpha-helical segment in the carboxy-terminal tail of sperm H1 which has amphipathic character due to the alanine distribution, and is likely to be curved, may be a special feature tailored to organize it. PMID- 2583127 TI - Replication origin of a single-stranded DNA plasmid pC194. AB - The replication of the single-stranded (ss) DNA plasmid pC194 by the rolling circle mechanism was investigated using chimeric plasmids that possess two pC194 replication origins. One of the origins was intact, whereas the other was either intact or mutated. The origins were activated by inducing synthesis of the pC194 replication protein, under the control of lambda phage pL promoter. Initiation of pC194 replication at one origin and termination at the other generated circular ssDNA molecules smaller than the parental chimeric plasmid. From the nature and the amount of ssDNA circles, the activity of an origin could be assessed. Our results show that (i) the signal for initiation of pC194 replication is more stringent than that for termination; (ii) the sequence and structure of the origin are important for its activity and (iii) successful termination of one replication cycle is not followed by reinitiation of another. This last observation differentiates a ssDNA plasmid (pC194) from a ssDNA phage (phi X174). PMID- 2583126 TI - Adenovirus VAI-RNA regulates gene expression by controlling stability of ribosome bound RNAs. AB - Adenovirus VAI-RNA is a small virally encoded RNA that is required for efficient protein synthesis at late times of adenoviral infection. We show that in transient transfection assays VAI-RNA promotes not only an increased level of protein encoded by a co-transfected marker (CAT) plasmid, but also a marked accumulation of its transcript. The increases in CAT protein and RNA levels reflect an enhanced stability of the cytoplasmic RNA as shown by primer extension analyses of RNA isolated from transfected cells upon transcriptional arrest. Surprisingly, the ability of VAI to activate expression of CAT requires the translation of a substantial portion of the RNA: when translation is prevented by elimination of the initiator AUG codon or by introduction of stop codons 5' to codon 107, VAI-RNA is no longer capable of increasing CAT RNA levels; the introduction of stop codons 3' of codon-135, on the other hand, does not significantly impair VAI-RNA function. We conclude that in addition to its role as a specific activator of translation, adenovirus VA genes function to regulate the stability of ribosome-bound RNA. PMID- 2583129 TI - Assays of three carcinogen/non-carcinogen chemical pairs for in vivo induction of chromosome aberrations, sister chromatid exchanges and micronuclei. AB - Three pairs of structurally similar carcinogenic/non-carcinogenic chemicals were tested for in vivo genotoxic activity in B6C3F1 mice. The carcinogenic/non carcinogenic pairs, respectively, were o-toluidine hydrochloride/o-anthranilic acid, 4-chloro-o-phenylenediamine/4-nitro-o-phenylenediamine, and 3 (chloromethyl)pyridine hydrochloride/2-(chloromethyl)pyridine hydrochloride. Bone marrow cells from mice given intraperitoneal injections of up to the maximum tolerated dose were evaluated for chromosomal aberration, sister chromatid exchange, and micronucleus induction, o-anthranilic acid and o-toluidine hydrochloride did not increase the frequency of chromosomal aberrations or micronuclei. o-Toluidine hydrochloride increased the frequency of sister chromatid exchanges in two successive trials, while o-anthranilic acid had a positive effect on sister chromatid exchanges in two of three trials. Both 2 (chloromethyl) and 3-(chloromethyl)pyridine hydrochloride were negative for all three endpoints. Assays for chromosomal aberrations and micronuclei each distinguished between 4-chloro-o-phenylenediamine and its non-carcinogenic companion, 4-nitro-o-phenylenediamine. In the aberration test, 4-chloro-o phenylenediamine produced a few cells with very large numbers of aberrations rather than an even distribution of damage among cells. PMID- 2583130 TI - Molecular analyses of in vivo hprt mutations in human T-lymphocytes: IV. Studies in newborns. AB - In order to characterize in vivo gene mutations that occur during fetal development, molecular analyses were undertaken of mutant 6-thioguanine resistant T-lymphocytes isolated from placental cord blood samples of 13 normal male newborns. These mutant T-cells were studied to define hypoxanthine-guanine phosphoribosyltransferase (hprt) gene structural alterations and to determine T cell receptor (TCR) gene rearrangement patterns. Structural hprt alterations, as shown by Southern blot analyses, occurred in 85% of these mutant clones. These alterations consisted mostly of deletion of exons 2 and 3. These findings contrast with the 10-20% of gross structural alterations (i.e., those visible on Southern blots) occurring randomly across the entire gene previously reported for T-cell mutants isolated from normal young adults. Iterative analyses of hprt structural alterations and TCR gene rearrangement patterns show that approximately one-third of the newborn derived mutants may have originated as pre or intrathymic hprt mutations. This too contrasts with previous findings in adults where the background in vivo hprt mutations appeared to originate in postthymic T-lymphocytes. PMID- 2583128 TI - Structure and deduced function of the granaticin-producing polyketide synthase gene cluster of Streptomyces violaceoruber Tu22. AB - A 6.5 kb region of DNA from Streptomyces violaceoruber, which contains polyketide synthase (PKS) genes for production of the benzoisochromane quinone moiety of the antibiotic, granaticin, was cloned and sequenced. Of six open reading frames (ORFs) identified, four (ORFs 1-4) would be transcribed in one direction and two (ORFs 5 and 6) divergently from ORFs 1-4. ORF1 and ORF2, which show evidence for translation coupling, encode (deduced) gene products which strongly resemble each other and the Escherichia coli fatty acid ketoacyl synthase (condensing enzyme), FabB. We conclude that ORF1 (which contains a characteristic cysteine residue) functions as a condensing enzyme, possibly as part of a heterodimeric protein including the product of ORF2. The predicted ORF3 gene product strikingly resembles acyl carrier proteins (ACPs) of fatty acid synthase (FAS), particularly in the region of the active site motif, while the predicted ORF5 and ORF6 gene products resemble known oxidoreductases, suggesting that they function as reductive steps required during assembly of the granaticin carbon skeleton. Comparison of the deduced ORF4 gene product with available protein databases failed to elucidate its potential function. The overall conclusion is that the granaticin-producing PKS would consist of at least six separate enzymes involved in carbon chain assembly, thus resembling a Type II, rather than a Type I, FAS. PMID- 2583132 TI - Serum fluoride in children anaesthetized with enflurane. AB - The serum inorganic fluoride concentration (SF) was measured in 40 children aged 22 days to 11 yrs (five infants) undergoing enflurane anaesthesia lasting 20-200 min, at an inspiratory concentration of 0.8 or 1.0%. Regardless of age, SF peaked at 2-8 mumol l-1 after 20-40 min of enflurane exposure, and at 4-10 mumol 1-1 and 6-10 mumol l-1 after 41-90 min and 91-200 min of exposure, respectively. The highest individual value was 12.5 mumol l-1. Another 23 children, aged 1-16 yrs, received 0.8% enflurane for 60 min. The increase in SF was 3-9 mumol l-1, with no clear dependence on age. Altogether, the increase in SF was comparable to that detected in adults after anaesthesia of equal duration. PMID- 2583133 TI - Posterior peribulbar anaesthesia for eye surgery. AB - The efficacy, reliability, and safety of a modification of posterior peribulbar blockade for various types of ophthalmic procedures were investigated. In the present prospective study we describe the technical conditions of a nerve block considered to be less dangerous for patients. The incidence of failure was low, there was no adverse reaction, and the patients themselves judged the method favourably. PMID- 2583131 TI - Chemical mutagenesis testing in Drosophila. VII. Results of 22 coded compounds tested in larval feeding experiments. AB - Twenty-two chemicals were tested for mutagenicity in the sex-linked recessive lethal (SLRL) mutation assay after being fed to Drosophila melanogaster larvae. One compound, maleic hydrazide, was found to be mutagenic. It was tested for the ability to produce reciprocal translocations (RTs) and was positive in that assay as well. PMID- 2583134 TI - The pharmacokinetics of intravenous anaesthetic drugs given by infusion: SPINA--a software program. AB - SPINA is a program developed with LOTUS 1-2-3 that simulates the pharmacokinetics of an infusion of intravenous anaesthetic drugs. SPINA incorporates a database which contains records of multiple-compartment pharmacokinetic models. The models have been obtained from the literature. They are directed towards those intravenous drugs that are used frequently during daily clinical anaesthetic practice. The models are classified using keywords for selection criteria (age, biometry, pathology and indication). To perform the pharmacokinetic simulation, the anaesthetist has to choose a pharmacokinetic model in which the program determines the turn-over rates, and displays a sequence of infusion steps. On request, SPINA provides the graphs for the theoretical drug distribution and for the infusion rate required to maintain the target concentration. SPINA therefore allows one to simulate the administration of intravenous anaesthetic drugs and to optimize their delivery. PMID- 2583135 TI - European Young Anaesthesia Researchers Group. 2nd meeting. Bonn, 31 August 1989. Abstracts. PMID- 2583136 TI - Anaesthetic induction in children. PMID- 2583137 TI - Contribution of central and reflex nervous activity to the rapid increase in pulmonary ventilation at the start of muscular exercise in man. AB - To investigate the relative contributions of the central and peripheral neural drive to hyperventilation at the onset of muscular exercise, five volunteers were tested during the first ten breaths while performing both voluntary (VM) and passive (PM) ankle rotations with a frequency of 1 Hz and through an angle of 10 degrees. Resulting breathing patterns for the two movements were compared. Hypocapnic hyperventilation, found in both PM and VM, indicated its neural origin. Respiratory changes were higher in VM than in PM. In both experimental conditions, increases in ventilation (VE) depended more on respiratory frequency (f) than on tidal volume (VT). Moreover, increases in VT adapted, breath-by breath, to values lower than the initial ones, while increases in f rose progressively. Expiratory time was reduced more than inspiratory time (TI); increases in inspiratory flow (VT/TI) depended to the same extent on changes in both TI and VT. Increases in expiratory tidal volume were initially higher than in inspiratory tidal volume, thereby producing a reduction in functional residual capacity. Because PM respiratory changes could be considered to be of nervous reflex origin only, the identical breathing patterns in PM and VM indicated that the hyperventilation found also in VM was mainly of reflex origin. The increase in VE was considered to be dependent on a greater stimulus from muscle proprioreceptors. PMID- 2583138 TI - Electromyography of lumbar erector spinae muscles--influence of posture, interelectrode distance, strength, and fatigue. AB - The aims of the study were to obtain information (1) on surface electromyograms (SEMG) from the lumbar erector spinae muscles at different interelectrode distances and postures during short isometric contractions with constant force, (2) on the relationships between SEMG and extension force at different postures, and (3) on changes in SEMG during fatiguing isometric contractions at different postures and strengths. Six male subjects developed target forces in prone postures without gravity confounding the measurement of the extension torque. The angles between the constantly horizontal upper trunk and thighs were 90 degrees (P1), 135 degrees (P2), 170 degrees (P3), and 190 degrees (P4). Standard deviations of the distribution of SEMG amplitudes (RMS values), autoregressive (AR) time series models of the 15th order and spectral densities, including mean power frequency (MPF), were computed. Smaller interelectrode distances accompanied smaller RMS values and higher MPF. At a constant extension torque of about 110 Nm, RMS values and MPF increased from P1 to P4. Changes of interelectrode distance were of relatively minor importance, compared with the variation in the posture. With increasing torque, the increase in RMS values was steeper at P3 than at P2. The AR structure and MPF did not exhibit distinct effects of force. During sustained contractions at P2 and P3, only the highest force (mean = 140 Nm) at P3 caused a significant decrease of the MPF at the very beginning of the contraction. Endurance at P2 was greater than at P3. Higher forces and/or shorter muscles (P3) induced more pronounced and earlier relative decreases of the MPF and residual variance of AR models. Up to the "failure point", RMS values increased slightly, but without significant differences. PMID- 2583139 TI - Thermoregulatory responses of firemen to exercise in the heat. AB - Twelve volunteer (VF) and 12 professional firemen (PF) wearing only brief trunks exercised on an electrically-braked cycle ergometer at three-five exercise intensities. After 45 min of exercise at 75 W, the exercise intensity was elevated in steps of 25 W every 15 min until the subject was exhausted. Air temperature was regulated to equal skin temperature (36 degrees-38 degrees C) and relative humidity was regulated at 52%. The two groups of firemen were comparable in terms of body mass, age and maximum oxygen consumption. Their oxygen consumption, rectal and skin temperatures, sweating and heart rate were measured during the tests. Blood lactate concentration was measured before, during and after the test. The physiological strain was higher in VF as indicated by higher heat storage, heart rate, skin and rectal temperatures. Sweat rate tended to be lower in VF than PF. The results indicated a better adaptation of the professional compared to the volunteer firemen to work in the heat, although the degree of heat acclimatization was considered to be equally minimal in both groups. PMID- 2583140 TI - Improved physical fitness failed to alter the EEG patterns of sleep in young women. AB - We investigated the effect of a 12-week physical training programme on the sleep of nine unfit women. Data were collected at 0, 4, 8 and 12 weeks of the training programme. Changes in fitness were assessed by changes in maximal oxygen consumption (VO2max) and onset of blood lactate turn point (LTP). Lean body mass (LBM) was calculated from total body potassium measurements. The all-night sleep recordings were made following days during which the subjects carried out their normal daily routines and did no extra exercise. Although cardiorespiratory fitness improved significantly as indicated by an increase in both VO2max and LTP, there was no change in LBM. The improvement in cardiorespiratory fitness did not result in any changes in the sleep parameters measured. Other workers have reported an improvement in sleep quality in eight army recruits during their basic training. The male recruits showed improved cardiorespiratory fitness and an increase in muscle bulk. These results suggest that increased fitness only facilitates sleep when there is an associated increase in LBM. Alternatively it may be that the response of sleep to improved fitness is sex-linked. PMID- 2583141 TI - In vivo vibrational wave propagation in human tibiae at different ages. AB - Vibrational wave propagation was tested in vivo on the tibial bone of both legs of 56 female volunteers. The impact was produced by a hammer with a force strain gauge and the response was monitored by two accelerometers. The peak amplitude of the accelerations, the velocity of the acceleration wave propagation and damping were analysed for comparison among the different age groups. The results showed significant negative correlations between age and the peak amplitude of acceleration, and the velocity of acceleration wave propagation (p less than 0.01). The damping time of the acceleration wave also had a negative correlation with age. These findings suggested that age differences were related to the differences in the mechanical properties of bone. With reduction of bone mineral density, the velocity of the vibrational wave propagation would decrease, with simultaneous increase in impedance. In addition, wave absorption would be accelerated. It is suggested that this method could be used as an indicator of bone density. The method could also be developed to provide an index to monitor the progress of osteoporosis. PMID- 2583142 TI - Influence of repeated passive body heating on subsequent night sleep in humans. AB - Experiments were carried out on four healthy male subjects in two separate sessions: (a) A baseline period of two consecutive nights, one spent at thermoneutrality [operative temperature (To) = 30 degrees C, dew-point temperature (Tdp) = 7 degrees C, air velocity (Va) = 0.2 m.s-1] and the other in hot condition (To = 35 degrees C, Tdp = 7 degrees C, Va = 0.2 m.s-1). During the day, the subjects lived in their normal housing and were engaged in their usual activities. (b) An acclimation period of seven consecutive daily heat exposures from 1400 to 1700 hours (To = 44 degrees C, Tdp = 29 degrees C, Va = 0.3 m.s-1). During each night, the subjects slept in thermoneutral or in hot conditions. The sleep measurements were: EEG from two sites, EOG from both eyes, EMG and EKG. Esophageal and ten skin temperatures were recorded continuously during the night. In the nocturnal hot conditions, a sweat collection capsule recorded the sweat gland activity in the different sleep stages. Results showed that passive body heating had no significant effect on the sleep structure of subsequent nights at thermoneutrality. In contrast, during nights at To = 35 degrees C an effect of daily heat exposure was observed on sleep. During the 2nd night of the heat acclimation period, sleep was more restless and less efficient than during the baseline night. The rapid eye movement sleep duration was reduced, while the rate of transient activation phases observed in sleep stage 2 increased significantly. On the 7th night, stage 4 sleep increased (+68%) over values observed during the baseline night.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583143 TI - Heart rate response to breath-holding during supramaximal exercise. AB - The cardiovascular responses to breath-holding (BH) during short-lasting supramaximal exercise (415 W) on a cycle ergometer were investigated in 15 healthy male subjects. The arterial oxygen saturation, heart rate (HR), endtidal PO2 and PCO2 were continuously monitored. Firstly, 15 subjects performed exercise during BH, preceded by air breathing (air-BH test), and secondly, exercise without BH. Then 9 of the subjects performed the same procedure as in the air-BH test, except that all subjects breathed 100% O2 for 1 min before apnoea (O2-BH test). In 2 of these subjects, the systemic arterial blood pressure was continuously measured via a catheter in the radial artery and plasma catecholamine concentration [CA] was also measured both during the air-BH and the O2-BH tests. In the later period of the air-BH test, the high HR level became progressively depressed. This response, however, was absent in the O2-BH test. There was a late increase in the arterial blood pressure in both tests, and both tests produced hypercapnia. Only the air-BH test resulted in hypoxia, substantial hypertension and HR-depression. The increase in plasma CA was similar in both tests. The marked HR-depression demonstrated here is ascribed mainly to activation of the peripheral arterial chemoreceptors by asphyxia, and partially to baroreceptor activity due to elevated blood pressure. PMID- 2583144 TI - Carbohydrate feeding and exercise: effect of beverage carbohydrate content. AB - The purpose of this study was to determine the effect of ingesting fluids of varying carbohydrate content upon sensory response, physiologic function, and exercise performance during 1.25 h of intermittent cycling in a warm environment (Tdb = 33.4 degrees C). Twelve subjects (7 male, 5 female) completed four separate exercise sessions; each session consisted of three 20 min bouts of cycling at 65% VO2max, with each bout followed by 5 min rest. A timed cycling task (1200 pedal revolutions) completed each exercise session. Immediately prior to the first 20 min cycling bout and during each rest period, subjects consumed 2.5 ml.kg BW-1 of water placebo (WP), or solutions of 6%, 8%, or 10% sucrose with electrolytes (20 mmol.l-1 Na+, 3.2 mmol.l-1 K+). Beverages were administered in double blind, counterbalanced order. Mean (+/- SE) times for the 1200 cycling task differed significantly: WP = 13.62 +/- 0.33 min, *6% = 13.03 +/- 0.24 min, 8% = 13.30 +/- 0.25 min, 10% = 13.57 +/- 0.22 min (* = different from WP and 10%, P less than 0.05). Compared to WP, ingestion of the CHO beverages resulted in higher plasma glucose and insulin concentrations, and higher RER values during the final 20 min of exercise (P less than 0.05). Markers of physiologic function and sensory perception changed similarly throughout exercise; no differences were observed among subjects in response to beverage treatments for changes in plasma concentrations of lactate, sodium, potassium, for changes in plasma volume, plasma osmolality, rectal temperature, heart rate, oxygen uptake, rating of perceived exertion, or for indices of gastrointestinal distress, perceived thirst, and overall beverage acceptance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583146 TI - Fitness as a determinant of oxygen uptake response to constant-load exercise. AB - Exercise performed above the lactate threshold (OLa) produces a slowly-developing phase of oxygen uptake (VO2) kinetics which elevates VO2 above that predicted from the sub-OLa VO2-work rate relationship. This phenomenon has only been demonstrated, to date, in subjects who were relatively homogeneous with respect to fitness. This investigation therefore examined whether this behaviour occurred at a given absolute VO2 or whether it was a characteristic of supra-OLa exercise in a group of subjects with over a threefold range of OLa (990-3000 ml O2.min-1) and peak VO2 (1600-5260 ml O2.min-1). Twelve healthy subjects performed: 1) exhausting incremental cycle ergometer exercise for estimation of OLa (OLa) and peak VO2, and 11) a series of constant-load tests above and below OLa for determination of the VO2 profile and efficiency of work. During all tests expired ventilation, VO2 and carbon dioxide production were monitored breath-by-breath. The efficiency of work determined during incremental exercise (28.1 +/- 0.7%, means +/- SE, n = 12) did not differ from that determined during sub-OLa constant load exercise (27.4 +/- 0.5%, p greater than 0.05). For constant-load exercise, VO2 rose above that predicted, from the sub-OLa VO2-work rate relationship, for all supra-OLa work rates. This was evident above 990 ml O2.min-1 in the least fit subject but only above 3000 ml O2.min-1 in the fittest subject. As a consequence the efficiency of work was reduced from 27.4 +/- 0.5% for sub-OLa exercise to 22.6 +/- 0.4% (p less than 0.05) at the lowest supra-OLa work rate (i.e. OLa + 20 W, on average).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583145 TI - Effects of an ultra-long-distance (1000 km) race on lipid metabolism. AB - The influence was examined of ultra-long-distance running (1000 km race lasting 20 days) on changes in serum lipids. The 110 participants received two types of diet, a conventional Western diet and a wholesome vegetarian diet. Of the 55 finishers the serum concentration of total cholesterol, low density lipoprotein (LDL)-cholesterol, apolipoprotein B and triglycerides decreased significantly during the first 8 days of the run, but rose again towards the end of the race without reaching pre-race levels. The high density lipoprotein (HDL)-cholesterol increased initially but decreased in the final days of the run. The values for apolipoprotein A-I were not correlated with HDL-cholesterol. The free fatty acids and free glycerol showed marked increases (five times the prerace concentration), falling towards the end of the run. Changes in serum lipids showed no correlation with changes in body mass. Similar changes were observed in both dietary groups. PMID- 2583147 TI - Circadian variations in psychophysiological responses to heat exposure and exercise. AB - Ten healthy men were tested at 0600, 1200, 1800 and 2400 hours on different days at rest in a laboratory at room temperature followed by 1 h of heat exposure in a climatic chamber at 42 degrees C, 60% rh (50 min rest and 10 min exercise on a cycle ergometer at 50% VO2max). Heart rate, blood pressure, rectal temperature Tre, metabolic rate, number connection test, visual and auditory reaction time, flicker test and catecholamine excretion were measured. Heat exposure and exercise caused lower heart rate acceleration at 2400 hours than at 0600 and 1200 hours, the smallest increase of Tre at 1800 hours, and an increase in metabolic rate greater at 1200 than at 1800 hours. In the afternoon, when, according to the circadian rhythm, the body temperature is highest, the additional heat load produced the smallest physiological effects. Performance efficiency, after heat exposure combined with physical exercise, improved slightly, but diurnal variations did not show significant circadian rhythm. PMID- 2583148 TI - On the edema-preventing effect of the calf muscle pump. AB - During motionless standing an increased hydrostatic pressure leads to increased transcapillary fluid filtration into the interstitial space of the tissues of the lower extremities. The resulting changes in calf volume were measured using a mercury-in-silastic strain gauge. Following a change in body posture from lying to standing or sitting a two-stage change in calf volume was observed. A fast initial filling of the capacitance vessels was followed by a slow but continuous increase in calf volume during motionless standing and sitting with the legs dependent passively. The mean rates of this slow increase were about 0.17%.min-1 during standing and 0.12%.min-1 during sitting, respectively. During cycle ergometer exercise the plethysmographic recordings were highly influenced by movement artifacts. These artifacts, however, were removed from the recordings by low-pass filtering. As a result the slow volume changes, i.e. changes of the extravascular fluid were selected from the recorded signal. Contrary to the increases during standing and sitting the calf volumes of all 30 subjects decreased during cycle ergometer exercise. The mean decrease during 18 min of cycling (2-20 min) was -1.6% at 50 W work load and -1.9% at 100 W, respectively. This difference was statistically significant (p less than or equal to 0.01). The factors which may counteract the development of an interstitial edema, even during quiet standing and sitting, are discussed in detail. During cycling, however, three factors are most likely to contribute to the observed reduction in calf volume: (1) The decrease in venous pressure, which in turn reduces the effective filtration pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583150 TI - The pattern of breathing and the ventilatory response to breathing through a tube and to physical exercise in sport divers. AB - Well-trained divers can be expected to differ from healthy controls in their ventilatory response to breathing through a tube and to physical exercise. Therefore, we measured their minute ventilation (VE) at rest and during breathing through a tube combined with two levels of physical exercise (1 or 2 W.kg body weight-1). For breathing through a tube an additional dead space of 600 ml was used. All divers were trained in the breath-hold technique and in the use of the breathing apparatus. Their mean period of training as divers was 9 +/- 6 years. The approximate age of the subjects was 25 years. The pattern of breathing and the oxygen uptake were measured by spirometer, the end-tidal concentration of CO2 was measured and all experiments were carried out above sea level. The ventilation of the divers at rest was comparable to that of the controls. During physical exercise it was smaller whether during breathing through a tube or not. The inadequate increase of VE during exercise in divers was associated with hypercapnia only at a higher physical work intensity (of 2 W.kg-1). This finding is interpreted as a lower chemoregulatory response to the combined stimuli of hypercapnia, hypoxia and physical exercise. In some situations significant bradypnoea and higher tidal volumes were found in the divers. PMID- 2583149 TI - The effects of substrate utilization, manipulated by caffeine, on post-exercise oxygen consumption in untrained female subjects. AB - The effect of substrate utilization manipulated by caffeine on post-exercise oxygen consumption was investigated in five untrained females (age = 21 +/- 1.5 years), following 90 min of treadmill walking at 55% maximal oxygen consumption. Each subject participated in the two trials (control and experimental) within 2 weeks of each other. Immediately following the measurement of resting oxygen consumption, subjects consumed one of the two test beverages 60 min prior to exercise: 5 mg of caffeine per kg of body-weight in 200 ml of orange juice (CA) or 200 ml of orange juice (C). Assignment of CA and C was made in a random, double blind fashion. Immediately prior to the exercise phase (0 min) resting oxygen consumption was again measured. Following exercise, subjects returned to the same pre-exercise sitting position where respiratory data was collected over 1 h. No significant differences were found in resting oxygen consumption and respiratory exchange ratio (R) prior to caffeine ingestion (-60 min). One hour after caffeine ingestion (0 min) oxygen consumption and free fatty acid (FFA) levels increased significantly compared to C. During and 1 h following exercise, oxygen consumption and FFA levels were significantly greater, with R values being significantly lower in CA compared to C. These findings provide further evidence that metabolic substrate is somehow implicated in elevating oxygen consumption following exercise cessation. PMID- 2583151 TI - Cardiorespiratory response to absolute and relative work intensity in untrained men. AB - Twenty young, untrained men performed two tests on cycle ergometer in order to verify whether the kinetics of the cardiorespiratory reactions exhibit any relation to maximal oxygen uptake (VO2max) in the untrained state. On the 1st day, the subjects exercised at work intensities of 50 and 100 W, the increase as a step function, for periods of 10 min each. The next day, they performed exercise at a relative intensity of 50% VO2max for 10 min. Respiratory frequency, tidal volume, minute ventilation (VE), heart rate (HR), stroke volume (SV), and cardiac output (Q) were measured continuously. The SV was measured by impedance plethysmography. All the cardiorespiratory variables increased rapidly at the onset of both absolute and relative intensity of work, with a faster response for Q than for VE. The increase in absolute intensity of work from 50 to 100 W caused a significantly slower cardiorespiratory reaction than at the beginning of exercise. The SV increased by 20 ml during first 20 s of both absolute and relative intensities of work and then began to decrease after 6 and 4 min of the exercise, respectively. The decrease in SV was associated with an increase in HR and a stable value of Q. Acceleration at the beginning of, and deceleration during recovery from, the relative intensity of work for VE, HR, and Q were well correlated with individual levels of VO2max in the tested men. It is concluded that the kinetics of cardiorespiratory reaction to a constant, relative intensity of work is related to VO2max in untrained men, and that the kinetics probably constitute a physiological feature of an individual. PMID- 2583152 TI - Effect of phototherapy on serum 25-hydroxyvitamin D in the Antarctic. AB - The hypothesis that sunlight may induce the enzymes involved in the vitamin D pathway has been tested by comparing the ability to synthesize vitamin D3 and its 25 hydroxy metabolite (25-OHD) in 2 groups of male volunteers resident at the British Antarctic base at Rothera Point (67 degrees 34'S.). One group endured the UV depleted winter and the other group received regular phototherapy throughout the winter. Both groups then received a course of 14 days phototherapy in October (Southern Hemisphere spring). The group receiving regular phototherapy had a trend towards a higher level of serum 25-OHD, and the October phototherapy course produced a further small increase in serum 25-OHD values. In the previously non irradiated group the October phototherapy produced a much larger increase in serum 25-OHD so that they attained the previously higher values of the pre iradiated group. There was a negative correlation between the pre October phototherapy serum concentration of 25-OHD and the subsequent increment (r-0.78, p less than 0.01) but no relationship between the serum 25-OHD and D3 after phototherapy. These results provide evidence against the existence of enzyme induction of vitamin D 25 hydroxylase by light. PMID- 2583153 TI - Blood lactate during submaximal exercises. Comparison between intermittent incremental exercises and isolated exercises. AB - Values of oxygen consumption, carbon dioxide production, ventilation and blood lactate concentration were determined in eight active male subjects during the minute following submaximal square-wave exercise on a treadmill under two sets of conditions. Square-wave exercise was (1) integrated in a series of intermittent incremental exercises of 4-min duration separated by 1-min rest periods; (2) isolated, of 4- and 12-min duration, and of intensity corresponding to each of the intermittent incremental periods of exercise. For square-wave exercise of the same duration (4 min) and intensity, no significant differences in the above mentioned parameters were noted between intermittent incremental exercise and isolated exercise. Only at high work rate (greater than 92% maximal oxygen uptake), were blood lactate levels in three subjects slightly higher after 12-min of isolated exercise than after the 4-min periods of isolated exercise. Examination of these results suggests that (1) 80-90% of the blood lactate concentration observed under our experimental conditions results from the accumulation of lactate in the blood during the period of oxygen deficit; (2) therefore the blood lactate concentration/exercise intensity relationship, for the most part, appears to represent the lactate accumulated early in the periods of intermittent incremental exercise. PMID- 2583154 TI - Influence of angular velocity and movement frequency on development of fatigue in repeated isokinetic knee extensions. AB - Six sedentary students, six orienteers, and six soccer players were each subjected to 15 tests, comprising 120 s of repeated, maximal isokinetic knee extensions. The tests differed with respect to movement velocity (30 degrees.s-1, 120 degrees.s-1, and 300 degrees.s-1), and movement frequency (5 at each velocity). At a certain velocity, a rectilinear relationship was found between muscular performance intensity (expressed either as average power output or as exercise time ratio) and development of fatigue (expressed either as an absolute or as a fractional decline in work output). Significant inter-velocity differences existed between the slopes of these lines at some combinations of performance and fatigue expressions. Only tendencies towards a difference in x intercept values were found. This x-intercept value can be taken as a measure of the greatest attainable intensity level of performance without the development of fatigue. This suggestion is valuable both in basic physiological research, and as a possible criterion for optimization of muscular performance. At a given exercise time ratio, increasing movement velocity produced increasing fatigue. However, at a given muscular power output--above 15 W approximately--fatigue developed to a greater extent at the low velocity than at the two higher ones, which did not differ significantly. Substantial individual variation was seen in the positions of the low-, medium-, and high-velocity lines. These variations did not depend on the training background. This implies that the validity of using single-velocity, single-frequency tests in determining isokinetic endurance is doubtful. PMID- 2583155 TI - Effect of liver disease on the kinetics of lactate removal after heavy exercise. AB - Recovery from heavy exercise requires clearance of lactic acid from the blood and body tissues. Although it has long been felt that the liver plays the major role in lactate removal, it has more recently been asserted that skeletal muscle plays the dominant role. We felt it relevant to this controversy to determine whether patients with liver dysfunction have slowed lactate removal following heavy exercise. Eight patients with alcoholic liver disease and 5 normal subjects were studied. Liver function was measured by the 14C-aminopyrine breath test; the results were expressed as the rate of appearance of 14CO2 in the breath two hours after ingestion, as a fraction of the ingested 14C dose (%.h-1). Each participant exercised on a cycle ergometer for 7 min at a work rate which was moderately heavy for that subject (mean peak lactate is 5.3 mmol.L-1). During, and for 45 minutes after exercise, blood was drawn from a hand vein catheter. The time required for blood lactate to decrease halfway toward resting levels (t1/2 LA) was determined. Compared to the normal subjects and historical controls, seven of the patients had distinctly slowed lactate removal. The t1/2 LA was as long as 46 min (as compared to approximately 15 min seen normally). Further, among the patients the 2 h breath excretion of 14C was well correlated with the rate constant of lactate removal (r 0.82, P less than 0.01). Four of the patients with severe liver dysfunction performed a second exercise test in which, instead of resting after heavy exercise, low level exercise was continued. The t1/2 LA of the averaged responses decreased by 29%.2+ PMID- 2583156 TI - Lipid profile of body builders with and without self-administration of anabolic steroids. AB - Twenty-four top-level body builders [13 anabolic steroid users (A); 11 non-users (N)] and 11 performance-matched controls (C) were examined to determine the effect on lipids, lipoproteins and apolipoproteins of many years of body building with and without simultaneous intake of anabolic steroids and testosterone. After an overnight fast, triglycerides (TG), total cholesterol (TOTC), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), the HDLC subfractions HDL2C and HDL3C, as well as apolipoprotein A-I (Apo A-I), apolipoprotein A-II (Apo A-II) and apolipoprotein B (Apo B) were determined. Both A and N, compared to C, showed significantly lower HDLC and higher LDLC concentrations, with the differences between A and C clearly pronounced. In a subgroup of 6 body builders taking anabolic steroids at the time of the study, HDLC, HDL2C, HDL3C, Apo A-I and Apo A-II were all significantly lower and LDLC was significantly higher than in a second subgroup of 7 body builders who had discontinued their intake of anabolic steroids at least 4 weeks prior to the study. In some single cases HDLC was barely detectable (2-7 mg.dl-1). The TG and TOTC remained unchanged. The present findings suggest that many years of body building among top-level athletes have no beneficial effect on lipoproteins and apolipoproteins. Simultaneous use of anabolic steroids results in part in extreme alterations in lipoproteins and apolipoproteins, representing an atherogenic profile. After discontinuing the use of anabolic steroids, the changes in lipid metabolism appear to be reversible. PMID- 2583157 TI - Exercise-induced activation of the branched-chain 2-oxo acid dehydrogenase in human muscle. AB - The present study was conducted to investigate the metabolic regulation of the oxidation of branched-chain amino acids (BCAA) by exercise in human skeletal muscle. Five trained male volunteers were exercised on a cycle ergometer at 70% +/- 10% (mean +/- SD) of their maximal oxygen consumption (VO2max). Percutaneous quadriceps muscle biopsies were obtained under local anaesthesia at rest and after 30 and 120 min of exercise. In the muscle samples the active and total amount of the branched-chain 2-oxo acid dehydrogenase complex (BC-complex), the regulatory enzyme in the oxidative pathway of the BCAA, were measured. Glycogen content and activity of mitochondrial marker enzymes were also measured. Blood samples were obtained every 20 min for the measurement of metabolites. Heart rate and rated perceived exertion on the Borg scale were recorded every 10 min. At rest 4.0% +/- 2.5% of the BC complex was active, after 30 min of exercise 9.9% +/ 9.0% and after 120 min 17.5% +/- 8.5% (mean +/- SD). Exercise did not change the total activity. The largest activation was seen in two of the subjects who developed higher blood lactates early on during exercise and decreased their muscle glycogen more (indications of anaerobic metabolism). These data demonstrate that in trained individuals significant increases in the activity of the BC-complex occur only after prolonged intense exercise. In spite of the 4 fold activation, the data support the classical view that amino acids and protein do not contribute substantially as an energy source during exercise, since VO2 increased more than 20-fold. PMID- 2583158 TI - The effect of caffeine ingestion on physical performance after prolonged exercise. AB - The purpose of this study was to determine the effect of caffeine ingestion on physical performance after prolonged endurance exercise. Twenty three trained male volunteers participated in a 40-km march and were divided into two groups, matched for caffeine clearance rate and aerobic capacity. The experimental group ingested, prior to the march, a caffeinated drink at a dose of 5 mg.kg-1 body mass and at the 3rd and 5th h of marching an additional drink at a dose of 2.5 mg.kg-1 body mass. The control group ingested a drink of equal volume at the same times. Upon termination of the march each subject performed a cycle ergometer test at an intensity of 90% maximal oxygen consumption. Time to exhaustion and rate of perceived exertion (RPE) were recorded. Blood samples were drawn predrink, at the 3rd and 5th h of marching and immediately after the cycle ergometer test, and were analysed for caffeine, free fatty acids (FFA), lactate and glucose levels. Plasma FFA levels increased during the march (p less than 0.05), with no significant difference between groups. Lactate levels increased in the experimental group (p less than 0.05), with no significant change in the control group. Glucose levels did not change significantly in either group. After the cycle ergometer test, lactate levels were significantly higher in the experimental, as compared to the control group (3.77 +/- 0.33 vs 2.52 +/- 0.35 mmol.l-1, respectively). There was no significant difference between treatments in the time to exhaustion on the cycle ergometer, but RPE was different (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583159 TI - Energy cost of running in similarly trained men and women. AB - The energy demand of running on a treadmill was studied in different groups of trained athletes of both sexes. We have not found any significant differences in the net energy cost (C) during running (expressed in J.kg-1.m-1) between similarly trained groups of men and women. For men and women respectively in adult middle distance runners C = 3.57 +/- 0.15 and 3.65 +/- 0.20, in adult long distance runners C = 3.63 +/- 0.18 and 3.70 +/- 0.21, in adult canoeists C = 3.82 +/- 0.34 and 3.80 +/- 0.24, in young middle-distance runners C = 3.84 +/- 0.18 and 3.78 +/- 0.26 and in young long-distance runners C = 3.85 +/- 0.12 and 3.80 +/- 0.24. This similarity may be explained by the similar training states of both sexes, resulting from the intense training which did not differ in its relative intensity and frequency between the groups of men and women. A negative relationship was found between the energy cost of running and maximal oxygen uptake (VO2max) expressed relative to body weight (for men r = -0.471, p less than 0.001; for women r = -0.589, p less than 0.001). In contrast, no significant relationship was found in either sex between the energy cost of running and VO2max. We conclude therefore that differences in sports performance between similarly trained men and women are related to differences in VO2max.kg-1. The evaluation of C as an additional characteristic during laboratory tests may help us to ascertain, along with other parameters, not only the effectiveness of the training procedure, but also to evaluate the technique performed. PMID- 2583160 TI - Cardiovascular and sympatho-adrenal responses to static handgrip performed with one and two hands. AB - 12 healthy men aged 21-25 years performed, in the sitting position, a sustained handgrip at 25% of their maximum voluntary contraction, first with each hand separately and then with both hands simultaneously. Heart rate (HR), systolic blood pressure (SBP), stroke volume (determined reographically) and plasma catecholamine concentration were measured during each handgrip test. The HR and SBP increased consistently during each handgrip test while stroke volume decreased by approximately 20% of the initial value. Cardiac output did not change significantly. There were no significant differences in the magnitude and dynamics of the cardiovascular responses between the tests with one and with both hands. Plasma noradrenaline and adrenaline levels showed similar elevations in response to handgrip performed with the right hand and with both hands, while during the exercise performed with the left hand the increase in the plasma catecholamine concentration was less pronounced. It was concluded that: (1) during sustained handgrip, performed in the sitting position by young healthy subjects, the stroke volume markedly decreases and cardiac output does not change significantly in spite of the increased HR; (2) the cardiovascular and sympatho adrenal responses to static handgrip do not depend on the mass of contracting muscle when the same relative tension is developed. PMID- 2583162 TI - Combined effects of vibration and noise on palmar sweating in healthy subjects. AB - The combined effects of vibration and noise on palmar sweating were studied experimentally in healthy subjects. Ten subjects were exposed to vibration at an acceleration of 100 m.sec-2 root mean square at a frequency of 125 Hz, a noise level of 105 dB(A) at a frequency of 1000 Hz and both stimuli together. Vibration was applied to the right hand and noise to both ears from headphones. Palmar sweating was measured by the ventilated capsule method. Vibration caused a marked increase in palmar sweating of the right hand directly exposed to vibration and also of the left hand not exposed to vibration. Simultaneous vibration and noise caused a greater increase in palmar sweating than by each of the factors separately. The combined effects tended to be greater in subjects who were more susceptible to vibration or noise. PMID- 2583161 TI - Post-exercise ketosis and the glycogen content of liver and muscle in rats on a high carbohydrate diet. AB - Post-exercise ketosis is known to be suppressed by physical training and by a high carbohydrate diet. As a result it has often been presumed, but not proven, that the development of post-exercise ketosis is closely related to the glycogen content of the liver. We therefore studied the effect of 1 h of treadmill running on the blood 3-hydroxybutyrate and liver and muscle glycogen concentrations of carbohydrate-loaded trained (n = 72) and untrained rats (n = 72). Resting liver and muscle glycogen levels were 25%-30% higher in the trained than in the untrained animals. The resting 3-hydroxybutyrate concentrations of both groups of rats were very low: less than 0.08 mmol.l-1. Exercise did not significantly influence the blood 3-hydroxybutyrate concentrations of trained rats, but caused a marked post-exercise ketosis (1.40 +/- 0.40 mmol.l-1 h after exercise) in the untrained animals, the time-course of which was the approximate inverse of the changes in liver glycogen concentration. Interpreting the results in the light of similar data obtained after a normal and low carbohydrate diet it has been concluded that trained animals probably owe their relative resistance to post exercise ketosis to their higher liver glycogen concentrations as well as to greater peripheral stores of mobilizable carbohydrate. PMID- 2583163 TI - Cardiovascular responses to autonomic stimuli in workers with vibration-induced white finger. AB - Cardiovascular responses to autonomic stimulation were assessed in 11 grinding operators affected with vibration-induced white finger (VWF) and in 11 comparable healthy controls by measuring blood pressures, heart rate and systolic time intervals (STI) during a hand-grip test, an arithmetic test and an orthostatic test. Digital circulatory function was also investigated by measurement of finger systolic pressure (FSP) during local cooling with water at 30 degrees C, 15 degrees C and 10 degrees C. The increase in diastolic blood pressure and heart rate during the stress tests was greater in the VWF workers than in the controls. The STI values such as total electromechanical systole and left ventricular ejection time, were found to be shorter in the VWF subjects than in the controls at rest and during both the circulatory stress tests and the recovery periods (0.001 less than p less than 0.05). Multiple regression analysis showed that vibration exposure was the major predictor of STI during the stress tests, while age, smoking and drinking habits did not contribute substantially to the explained variation in STI. The reduction in FSP by local cooling from 30 degrees C to 15 degrees C and 10 degrees C was greater in VWF operators than in controls (p less than 0.001), and total closure of the digital arteries at 10 degrees C was observed in 8 VWF workers (72.7%). In all subjects significant relationships were found between the reduction in FSP at 10 degrees C and the decrease in STI during circulatory stress activities (p less than 0.001). The findings in this study suggest an association between vibration exposure, digital vasospasm and increased cardiac sympathetic tone, the latter being demonstrated by the shortening of STI during the stress tests. It is suggested that excessive sympathetic reflex activity plays the dominant role in the pathogenesis of VWF. PMID- 2583164 TI - Aging process of leg muscle endurance in males and females. AB - In order to estimate muscle endurance during knee extension (KME) and plantar flexion (PME) using a simple method, holding times for the half-squatting posture for KME and for the calf-raising posture for PME were measured in 3,792 males and 3,620 females aged between 6 and 79 years. The regression lines of the aging process for KME and PME in both sexes were determined. Peak values were found at 13 years in males and 12 years in females for KME, and at 15 years in males and 16 years in females for PME. The mean values increased sharply with age up to each peak and then decreased abruptly to a low level at around 20 years, thereafter declining gradually. The values of KME as a percentage of the peak value were 71, 75 and 34 at the ages of 6, 20 and 70-79 years respectively in males, while the corresponding values were 80, 77 and 36 for females. The values of PME at these ages were 34, 93 and 69 in males and 54, 91 and 73 in females. The mean values for males were generally higher than those for females. These results suggest that endurance of the leg muscles differs according to age, sex and the region of the leg muscle. These data will be useful as standard values for evaluating endurance and for prescribing suitable exercise for the promotion of physical fitness. PMID- 2583165 TI - Muscle cross-sectional area and voluntary force production characteristics in elite strength- and endurance-trained athletes and sprinters. AB - Seven male elite strength-trained athletes (SA) from different weight categories, six elite sprinters (SPA) and seven elite endurance-trained athletes (EA) volunteered as subjects for examination of their muscle cross-sectional area (CSA), maximal voluntary isometric force, force-time and relaxation-time characteristics of the leg extensor muscles. The SA group demonstrated slightly greater CSA and maximal absolute strength than the SPA group, while the EA group demonstrated the smallest values both in CSA and especially in maximal strength (p less than 0.05). When the maximal forces were related to CSA of the muscles, the mean value for the SA group of 60.8 +/- 10.0 N.cm-2 remained slightly greater than that recorded in the SPA group 55.0 +/- 3.1 N.cm-2 and significantly greater (p less than 0.05) than that recorded in the EA group 49.3 +/- 4.0 N.cm-2. The mean value in the SPA was also significantly greater (p less than 0.05) than that of the EA group. The isometric force-time curves differed between the groups (p less than 0.05-0.01) so that the times taken to produce the same absolute force were the shortest in the SPA group and the longest in the EA group. With force expressed as a percentage of the maximum, the force-time curves showed that the SPA group demonstrated still shorter times to a given value (p less than 0.05), especially at the lower force levels, than the other two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583166 TI - Quantitative correlation between cardiovascular and plasma epinephrine response to mental stress. AB - To investigate the quantitative correlations between cardiovascular and endogenous catecholamine response to mental stress, we gave a mental arithmetic test to 20 young healthy men. A direct and non-invasive haemodynamic measurement was performed by serial M-mode echocardiography. Heart rate, blood pressure, cardiac output, stroke volume, ejection fraction, left ventricular end-systolic pressure-volume ratio and plasma epinephrine increased over the baseline period during the test. The peripheral resistance and left ventricular end-systolic volume decreased, whereas left ventricular end-diastolic volume and plasma norepinephrine were unaltered. Furthermore, the degree of change in each haemodynamic parameter showing significant reaction, was well correlated with that of the increase in plasma epinephrine. The data suggest that acute mental stress induces endogenous epinephrine secretion resulting in a beta-adrenergic activated state in the cardiovascular system, namely, positive chronotropism, positive inotropism and vasodilatation. PMID- 2583167 TI - Bilateral eccentric and concentric torque of quadriceps and hamstring muscles in females and males. AB - This study assessed maximum eccentric (ECC) and concentric (CON) torque of quadriceps (QUAD) and hamstring (HAM) muscle groups in healthy females (n = 13) and males (n = 27). Peak torques (PT) of bilateral muscle actions were recorded at constant angular velocities of 0.52, 1.57 and 2.61 rad.s-1. The QUADCON and HAMCON PT decreased (p less than 0.05) with increasing angular velocity. The QUADECC and HAMECC PT increased (p less than 0.05) in females, whereas QUADECC PT decreased (p less than 0.05) and HAMECC PT showed no change in males. In general, ECC PT was higher (p less than 0.05) than CON PT and QUAD PT was higher (p less than 0.05) than HAM PT, for any given angular velocity. Males displayed higher (p less than 0.05) PT than females but when PT were adjusted for body mass the sex differences in QUADCON and HAMCON were reduced (p less than 0.05), whereas the differences in QUADECC and HAMECC were abolished. The CON and ECC PT were, on average, 60% and 41% greater, respectively, in males than in females. The corresponding differences, when adjusted for body mass, were 23% and 8%. ECC:CON PT for QUAD were higher (p less than 0.05) in females than in males. CON and ECC HAM:QUAD PT ratio increased (p less than 0.05), as a function of velocity. This study suggests, that bilateral ECC PT is higher than CON PT and CON HAM:QUAD PT ratio is higher than ECC HAM:QUAD PT ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583168 TI - Serum hormone concentrations during prolonged training in elite endurance-trained and strength-trained athletes. AB - A study of 1 year was performed on nine elite endurance-trained athletes (swimmers) and on eight elite strength-trained athletes (weightlifters) in order to examine the effects of training on the endocrine responses and on physical performance capacity. The measurements for the determination of serum hormone concentrations were performed at about 4-month intervals during the course of the year. The primary findings demonstrated that during the first and most intensive training period of the year in preparing for the primary competitions similar but statistically insignificant changes were observed in the concentrations of serum testosterone, free testosterone and cortisol in both the endurance-trained and strength-trained groups. After that period the changes in hormonal response over the year were infrequent and minor. A significant (p less than 0.01) decrease occurred in the strength-trained group in serum-free testosterone during the second period, which was characterized by the highest overall amount of training. Over the entire year the concentrations of serum hormones remained statistically unaltered in both groups. Slight but statistically insignificant increases of 1.2% +/- 0.8% and 2.1% +/- 5.1% were observed in the competitive performances over the year in the endurance-trained and strength-trained groups, respectively. The present findings in the two groups of elite athletes, who differed greatly with regard to the type of physiological loading, demonstrated that the overall hormonal responses both during the most intensive and during prolonged training periods were rather similar and the infrequent small changes remained well within the normal physiological range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583169 TI - Effect of disuse on the ultrastructure of the achilles tendon in rats. AB - We examined the influence exerted, through disuse of the hindlimb, on the collagen fibres of the achilles tendon in rats. With disuse the body mass decreased by 28%, and the mass of soleus muscle decreased by 20%. A decrease in the surface area and diameter was observed in the experimental group when compared to the control group. A histogram of the collagen fibres showed a decrease of the thick fibres in the experimental group. The maximum surface area of collagen fibres in the experimental group was seen to be only 43% of that of the control group. These results showed a decrease in the thickness of the collagen fibres of the achilles tendon through disuse. This seemed to suggest that resistance to tension is decreased by disuse. PMID- 2583170 TI - Effects of vibration on arm and shoulder muscles in three body postures. AB - The electromyographic responses of arm and shoulder muscles to vibrations were studied in three postures similar to the postures of drilling in a ceiling, drilling in a wall and drilling in a floor. This experiment was performed within the defined parameters of: vibrational frequency at 30 Hz, acceleration level 40 m.s-2 (rms), pushing force expressed as percentage maximal voluntary contraction, and gripping force which was set at 100 N. The exposure time for each test was 5 min. The general findings from these three body postures show that all the examined muscles were affected by exposure to vibration. The EMG index increased as follows: trapezius muscle 39% (p less than 0.05), lower-arm flexor muscles 23% (p less than 0.05), infraspinatus muscle 14% (p less than 0.05), lower-arm extensor muscles 14% (p less than 0.1) and biceps muscle 6% (p less than 0.1). The muscle most affected by vibration was found to be the trapezius muscle. It should be taken into consideration that vibration can be a contributing factor in neck/shoulder disorders among power handtool operators. The general conclusion from this study is that changes in working posture give different transmissions of vibration in the upper extremities. It seems as if the prime movers and muscles with an increased muscle length or increased degree of contraction are most affected by vibration. PMID- 2583171 TI - Lipolytic response of adipocytes to epinephrine in sedentary and exercise-trained subjects: sex-related differences. AB - Adipose tissue lipolytic activity is increased in endurance-trained subjects, but little is known about the mechanisms of this increase. To understand more fully the mechanisms involved and to discover whether sex-related differences exist, biopsies of fat were performed in the periumbilical region of 20 sedentary subjects (10 women (W) and 10 men (M)) and 20 trained subjects (10 W, 10 M); the in vitro response to epinephrine of the collagenase-isolated fat cells was studied. Glycerol release, chosen as an adipocyte lipolysis indicator, was measured by bioluminescence. Dose-response curves with epinephrine (alpha 2 and beta agonist), with isoproterenol (beta agonist) and epinephrine + propranolol and adenosine deaminase, were studied. Epinephrine-induced lipolysis was enhanced in trained subjects and this was due to an increased efficiency of the beta adrenergic pathway. However, differences were found between the two sexes. In trained men, the lipolysis increase resulted from the enhancement of the beta adrenergic pathway efficiency without any significant decrease in the alpha 2 adrenergic pathway efficiency. In trained women, the lipolysis increase was not only due to the enhancement of the beta-adrenergic pathway efficiency (which was greater than in trained men), but also to a significant decrease in the alpha 2 adrenergic pathway efficiency. Despite the decrease, the alpha 2-adrenergic pathway remained more efficient in trained women than in trained men, as was the case in sedentary subjects. It is concluded that endurance training led to better lipid mobilization and that this effect seemed greater in women than in men. PMID- 2583172 TI - Blood lactate responses in incremental exercise as predictors of constant load performance. AB - Seven trained male cyclists (VO2max = 4.42 +/- 0.23 l.min-1; weight 71.7 +/- 2.7 kg, mean +/- SE) completed two incremental cycling tests on the cycle ergometer for the estimation of the "individual anaerobic threshold" (IAT). The cyclists completed three more exercises in which the work rate incremented by the same protocol, but upon reaching selected work rates of approximately 40, 60 and 80% VO2max, the subjects cycled for 60 min or until exhaustion. In these constant load studies, blood lactate concentration was determined on arterialized venous ([La-]av) and deep venous blood ([La-]v) of the resting forearm. The av-v lactate gradient across the inactive forearm muscle was -0.08 mmol.l-1 at rest. After 3 min at each of the constant load work rates, the gradients were +0.05, +0.65* and +1.60* mmol.l-1 (*P less than 0.05). The gradients after 10 min at these same work rates were -0.09, +0.24 and +1.03* mmol.l-1. For the two highest work rates taken together, the lactate gradient was less at 10 min than 3 min constant load exercise (P less than 0.05). The [La-]av was consistently higher during prolonged exercise at both 60 and 80% VO2max than that observed at the same work rate during progressive exercise. At the highest work rate (at or above the IAT), time to exhaustion ranged from 3 to 36 min in the different subjects. These data showed that [La-] uptake across resting muscle continued to increase to work rates above the IAT. Further, the greater av-v lactate gradient at 3 min than 10 min constant load exercise supports the concept that inactive muscle might act as a passive sink for lactate in addition to a metabolic site. PMID- 2583173 TI - Effects of endurance training on hyperammonaemia during a 45-min constant exercise intensity. AB - Eleven laboratory-pretrained subjects (initial VO2max = 54 ml.kg-1.min-1) took part in a study to evaluate the effect of a short endurance training programme [8 12 sessions, 1 h per session, with an intensity varying from 60% to 90% maximal oxygen consumption (VO2max)] on the responses of blood ammonia (b[NH+4]) and lactate (b[la]) concentrations during progressive and constant exercise intensities. After training, during which VO2max did not increase, significant decreases in b[NH+4], b[la] and muscle proton concentration were observed at the end of the 80% VO2max constant exercise intensity, although b[NH+4] and b[la] during progressive exercise were unchanged. On the other hand, no correlations were found between muscle fibre composition and b[NH+4] in any of the exercise procedures. This study demonstrated that a constant exercise intensity was necessary to reveal the effect of training on muscle metabolic changes inducing the decrease in b[NH+4] and b[la]. At a relative power of exercise of 80% VO2max, there was no effect of muscle fibre composition on b[NH+4] accumulation. PMID- 2583174 TI - The relationship between anaerobic threshold and heart rate linearity during cycle ergometry. AB - Recent studies have demonstrated there is a definitive deflection in the heart rate response to incremental velocity work that coincides with the anaerobic threshold. These studies were conducted with elite athletes who performed the specific activities in which they were trained. The purpose of this study was to determine if the same relationship in heart rate and ventilatory response to increasing velocity was evident in nine untrained healthy subjects aged 22 to 36 years performing leg ergometry under controlled laboratory conditions. All subjects began pedaling at 50 rpm with an initial power output of 100 W. Pedaling rates were increased by 5 rpm every 30 s. This increment was equivalent to a power increase of 11.1 W. The subjects cycled to the point of exhaustion or until they could no longer maintain the pedaling speed at the higher velocities. Heart rate and expiration gases were collected at 30-s intervals. The results indicated that the heart rate and ventilatory response to increasing velocity as previously reported under field conditions does not exist under laboratory conditions. While there was a definitive and statistically significant inflection in the ventilatory response to increasing velocity, heart rate remained linear. Therefore, caution should be used when determining the anaerobic threshold from the single measure of heart rate response. PMID- 2583175 TI - Effect of low frequency fatigue on human muscle strength and fatigability during subsequent stimulated activity. AB - Fatiguing contractions of the adductor pollicis muscle were produced by intermittent supramaximal stimulation of the ulnar nerve in a set frequency pattern, in six normal subjects. At the end of an initial fatiguing contraction series, low frequency fatigue (LFF) had been induced and persisted at 15 min of recovery. Stimulated fatiguing activity was then repeated in an identical fashion to the initial series. At high frequencies, declines in force were similar for both series. At low frequencies, declines in force were greater during the second series despite similar changes in compound muscle action potential amplitude. This confirmation that LFF persists during subsequent stimulated activity, and reduces low but not high frequency fatigue resistance, suggests that the impaired endurance of fatigued muscle during voluntary activity primarily results from peripheral changes at low frequency. These findings also have implications for therapeutic electrical stimulation of muscle. PMID- 2583176 TI - Mean skin temperature in warm humid climates. AB - Mean skin temperature (Tsk) was measured in 24 subjects during experiments in a climatic chamber. Three conditions of ambient temperature (Ta = 25.6 degrees, 28.9 degrees and 32.2 degrees C), and three of humidity (relative humidity = 50%, 70% and 90%) were studied. A relationship was established by a linear regression technique. It is valid in the 24 degree-34 degree C range, for air velocity = 0.2 m.s-1, clothing insulation = 0.077 degrees C.m2.w-1 (0.5 clo), metabolic rate = 64 w.m-2 (1.1 met) and radiant temperature = air temperature. In these conditions Tsk = 28.125 + 0.021 Pw + 0.210 Ta (Pw: ambient water vapour pressure in mb). It shows a small humidity influence. The influences of sex, transition from one condition to the next, and air velocity were also studied. Measurements in Africa confirmed the small influence of humidity. Ethnic life-style differences indicated that a high precision in Tsk determination is difficult to achieve. PMID- 2583177 TI - Thermal stress and physiological strain of children exposed to hot environments in a glass bangle factory. AB - A group of 19 male children (mean age 12.1 years SEM 1.6 years) occupationally exposed to an excessively hot environment for an average duration of 2.5 years SEM 1.7 years in the glass bangle factory in Firozabad, India, were studied to evaluate the physiological strain induced by the thermal radiation (mean radiant temperature 46.2 degrees SEM 5.1 degrees C) and high ambient temperature (38.2 degrees SEM 3.4 degrees C) prevailing in the factory. Over a work-shift the mean increase in oral temperature was 0.90 degrees C in the exposed children, in comparison with the 0.40 degrees C increase recorded in the control children (p less than 0.05). The maximum increase in oral temperature was recorded in 'gulliwalas' (0.90 degrees C) and the minimum in 'battiwalas' (0.80 degrees C). The mean peak value of oral temperature (37.5 degrees C) was observed at 1600 hours. A significant increase in the pulse rate (25.9 beats.min-1) during the work-shift was observed in the exposed children in comparison with a mean increase of 9.4 beats.min-1 in the control group. Ventilatory studies showed pulmonary hyperventilation in the exposed workers. The increase in pulmonary ventilation was in the form of an increase in tidal volume and respiratory frequency induced by high environmental temperatures and thermal radiation. The cardio-respiratory responses showed physiological strain induced by the high ambient temperature and radiant heat prevailing in the glass bangle factory. PMID- 2583178 TI - The relationship between contraction and relaxation during fatiguing isokinetic shoulder flexions. An electromyographic study. AB - Knowledge of the strength, endurance and coordination of the shoulder muscles during dynamic contractions in healthy women would contribute to the understanding of symptoms in that part of the body in patients with myalgia. Twenty clinically healthy women performed single maximal forward shoulder flexions at four different angular velocities (0.57-3.14 rad.s-1). The same subjects also took part in two endurance tests (at angular velocities of 0.57 and 2.09 rad.s-1, respectively) consisting of 150 repeated maximal shoulder flexions. Electromyographic activity (EMG) was registered from four shoulder flexors using surface electrodes. Work was used as the mechanical variable. During the endurance tests subjects rated their perception of fatigue in the shoulder muscles. Work and the amplitude of the EMG signals decreaesd with angular velocity. The mean power frequency of the EMG was constant in the span of angular velocities investigated. During the endurance tests, work and the mean power frequency decreased during the initial 40-60 contractions followed by stable levels. The relative work level was higher at 2.09 than at 0.57 rad.s-1. Greater relative increases of the signal amplitudes of EMG occurred at 2.09 than at 0.57 rad.s-1. The EMG activity between the flexions (during the supposed passive extension) was higher at 2.09 than at 0.57 rad.s-1. Such a high activity was associated with a low mechanical performance at 2.09 rad.s-1. It is suggested that the initial sharp decreases in work and in mean power frequency reflect the fatiguing of the fast twitch motor units. Dynamic work consisting of continuous activity could predispose to muscle complaints. PMID- 2583180 TI - Biosynthesis of 1-alkenes in higher plants: stereochemical implications. A model study with Carthamus tinctorius (Asteraceae). AB - Odd numbered 1-alkenes, such as 1-pentadecene or 1,8,11,14-heptadecatetraene are formed from palmitic or linolenic acid by fragmentative decarboxylation. Incubation studies with germinating safflower (Carthamus tinctorius) and (2R,3R) 12-phenyl[2,3-2H2]dodecanoic acid, (2S,3S)-12-phenyl[2,3-2H2]dodecanoic acid, (2R)-12-phenyl[2-2H]dodecanoic acid and (2S)-12-phenyl[2-2H]dodecanoic acid instead of the natural alpha-linolenic acid precursor revealed the fragmentation to be an overall anti elimination of the 3-pro(S) hydrogen and the carboxyl group (anti-periplanar transition state geometry). Externally offered 3-hydroxy acids are not fragmented to 1-alkenes. The most probable mechanistic alternatives are in agreement with abstraction of the 3-pro(S) hydrogen as a radical followed by electron transfer and fragmentation, or transient insertion of oxygen into the 3 pro(S) C-H bond and subsequent fragmentation into an 1-alkene and CO2 after appropriate activation. The mechanism seems to be of general importance for the biosynthesis of vinylic substructures of natural products from oxygenated precursors. PMID- 2583179 TI - Changes in force, cross-sectional area and neural activation during strength training and detraining of the human quadriceps. AB - Four male subjects aged 23-34 years were studied during 60 days of unilateral strength training and 40 days of detraining. Training was carried out four times a week and consisted of six series of ten maximal isokinetic knee extensions at an angular velocity of 2.09 rad.s-1. At the start and at every 20th day of training and detraining, isometric maximal voluntary contraction (MVC), integrated electromyographic activity (iEMG) and quadriceps muscle cross sectional area (CSA) assessed at seven fractions of femur length (Lf), by nuclear magnetic resonance imaging, were measured on both trained (T) and untrained (UT) legs. Isokinetic torques at 30 degrees before full knee extension were measured before and at the end of training at: 0, 1.05, 2.09, 3.14, 4.19, 5.24 rad.s-1. After 60 days T leg CSA had increased by 8.5% +/- 1.4% (mean +/- SEM, n = 4, p less than 0.001), iEMG by 42.4% +/- 16.5% (p less than 0.01) and MVC by 20.8% +/- 5.4% (p less than 0.01). Changes during detraining had a similar time course to those of training. No changes in UT leg CSA were observed while iEMG and MVC increased by 24.8% +/- 10% (N.S.) and 8.7% +/- 4.3% (N.S.), respectively. The increase in quadriceps muscle CSA was maximal at 2/10 Lf (12.0% +/- 1.5%, p less than 0.01) and minimal, proximally to the knee, at 8/10 Lf (3.5% +/- 1.2%, N.S.). Preferential hypertrophy of the vastus medialis and intermedius muscles compared to those of the rectus femoris and lateralis muscles was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583181 TI - Two arylamine N-acetyltransferases from chicken pineal gland as identified by cDNA cloning. AB - A cDNA library prepared from the poly(A)-rich RNA of the chicken pineal gland obtained at night was screened with the 32P-labeled cDNA of arylamine N acetyltransferase from the chicken liver recently isolated in this laboratory. Two positive clones (p-NAT-3 and p-NAT-10) that cross-hybridized with the liver cDNA were isolated. The cDNAs did not cross-hybridize each other under a high stringency, indicating that they corresponded to different mRNAs. When the cDNAs were inserted into an expression vector pcDL1 under the control of the early promoter of simian virus 40 and introduced into Chinese hamster ovary cells, both cDNAs expressed arylamine N-acetyltransferase activity in the transfected cells. The nucleotide sequences of the cDNAs were determined, from which amino acid sequences were deduced. Both cDNAs coded for 290 amino acids. Similarities in amino acid sequences were about 60% between p-NAT-3, p-NAT-10 and liver N acetyltransferases. Poly(A)-rich RNA blot hybridization analysis indicated that p NAT-3 cDNA detected a 2.2-kb band with the poly(A)-rich RNAs from the brain, gut and, less intensively, spleen, liver and kidney, while p-NAT-10 cDNA hybridized only with the poly(A)-rich RNA from the kidney. Neither cDNA detected any hybridization band with the poly(A)-rich RNA from the pineal gland, suggesting that the contents were low. Genomic Southern blot hybridization analysis showed that p-NAT-3, p-NAT-10 and liver N-acetyltransferases were encoded in a separate single gene. The properties of the enzymes expressed in the transfected cells were compared with N-acetyltransferases from the pineal gland, brain and kidney. On a DEAE-cellulose column, the kidney and p-NAT-10 enzymes appeared in the effluent fraction, whereas the brain and p-NAT-3 enzymes were eluted from the column with a gradient elution at 0.08 M NaCl. The supernatant of the pineal gland obtained in the daytime showed two peaks appearing in the effluent fraction and the eluate fraction at 0.08 M NaCl. The substrate specificity of these enzymes were examined with p-phenetidine, 2-aminofluorene, tryptamine and phenylethylamine as substrates. All the enzymes preferred arylamines to arylalkylamines, indicating that both p-NAT-3 and p-NAT-10 cDNAs encoded arylamine N-acetyltransferases. PMID- 2583182 TI - Tryptophan 110, a residue involved in the toxic activity but not in the enzymatic activity of notexin. AB - We prepared two derivatives of notexin, a phospholipase A2 from Notechis scutatus scutatus venom, by modifying the protein with 2-nitrophenylsulfenylchloride, a tryptophan-specific reagent. One derivative was modified at both tryptophans 20 and 110 whereas the other was modified at tryptophan 20. Evidence based on circular dichroic analysis and antigenicity towards a notexin-specific monoclonal antibody indicated that derivatization at both tryptophans did not affect the tertiary structure of notexin. Concomitant modification of tryptophans 20 and 110 induced a marked decrease in the capacity of notexin to kill mice and to block neuromuscular transmission in the chick biventer cervicis preparation, whereas selective modification at tryptophan 20 had no effect on the lethal properties of notexin. This implies that the decrease in the lethal properties of notexin after derivatization was due to modification at tryptophan 110. However, the diderivatized notexin retained full enzymatic activity, implying that neither tryptophan 20 and tryptophan 110 are involved in the catalytic function of the molecule. We conclude that notexin harbours two functional sites. One of them corresponds to the enzymatic site, whereas the other, which includes tryptophan 110, provides specific toxic characteristics to notexin. By reference to previous crystallographic studies, the relative spatial positions of elements involved in toxicity and the catalytic site, we propose a possible orientation of notexin with respect to its putative membrane-bound target. PMID- 2583183 TI - Molecular organization and clustering of cell-wall-bound enzymes as a source of kinetic apparent co-operativity. AB - When fixed charges and enzyme molecules are not homogeneously distributed in a matrix, the degree of organization of charges, of enzyme molecules and of charges with respect to enzyme molecules modulate the enzyme reaction rate. The overall reaction velocity of the bound enzyme system may be expressed in terms of monovariate moments of the charge density distribution and of the bivariate moments of the charge and enzyme density distributions. With respect to the situation where fixed charges and enzyme molecules are randomly distributed in the matrix, the molecular organization, as expressed by the monovariate and bivariate moments results in an increase or a decrease, of the overall reaction rate, as well as in the appearance of a kinetic cooperativity. The degree of spatial organization of objects may be expressed quantitatively through the concept of minimal spanning tree. This concept may thus be applied to the quantification of the degree of order that may exist in the bidimensional distribution of enzyme molecules in a charged matrix. Primary walls of isolated plant cells in sterile culture behave as a polyanion and contain different enzymes. The spatial distribution in sycamore cell walls of an acid phosphatase has been studied through the concept of minimal spanning tree and shown to be non randomly distributed in the polyanionic matrix, but clustered in that matrix. This spatial organization results in a modulation of the reaction rate of the cell-wall-bound phosphatase reaction. Both the theoretical and experimental results presented in this study leave little doubt as to the validity of the idea that in situ the organization of fixed charges and enzyme molecules modulate the overall dynamics of enzyme reactions. PMID- 2583184 TI - Characterization of mononuclear-phagocyte terminal maturation by mRNA phenotyping using a set of cloned cDNA probes. AB - The terminal step in the maturation of mononuclear cells from circulating monocytes to resident macrophages is accompanied by dramatic changes in cell morphology and physiology. Applying a cultivation system which allows peripheral monocytes to undergo terminal maturation in vitro under absolutely endotoxin-free conditions, we have determined the pattern of expression of a set of eight genes by mRNA phenotyping. The results can be summarized as follows: the two protease inhibitors alpha 1-antitrypsin and alpha 2-macroglobulin show a inverse pattern of expression. alpha 1-Antitrypsin mRNA is repressed, alpha 2-macroglobulin mRNA is strongly induced during maturation to macrophages. Therefore, these two genes are excellent markers of the terminal maturation. In addition, ferritin-light chain mRNA progressively increases during the course of differentiation, providing a further marker for maturation. Gene expression as a function of activation was studied in mononuclear cells stimulated with bacterial endotoxin (lipopolysaccharide). In monocytes, complement-factor-B, interleukin-1 and interleukin-6 mRNAs are drastically induced upon lipopolysaccharide activation whereas lysozyme RNA is strongly repressed. However, the ability of all four genes to respond to endotoxin was markedly diminished or abolished in mature macrophages, indicating that susceptibility to a certain type of activation may be restricted to a specific stage of maturation. Our data show that mRNA phenotyping is excellently suited for the characterization of the differentiation and activation state of mononuclear phagocytes. PMID- 2583185 TI - Tissue specificity of nucleo-cytoplasmic distribution of HMG1 and HMG2 proteins and their probable functions. AB - The levels and distribution between nucleus and cytoplasm of HMG1 and HMG2 proteins have been investigated in different tissues of mammals. In lymphoid tissues and testis high amounts of these proteins are present in both nuclei and cytoplasm, while in the hepatic tissues and brain they accumulate in cytoplasm, mainly in the cytosol. In particular, very low amounts, if any, of HMG1 and 2 are present in the nuclei active for DNA replication (rat regenerating liver and primary hepatoma) or transcription (adult liver and brain). Therefore, it appears that HMG1 and 2 are not necessary for these processes. On the other hand, nuclear (chromosomal) HMG1 and 2 are characteristic for the tissues containing undifferentiated cells: lymphoid tissues, testis, neonatal liver. These proteins are bound to the chromatin regions solubilized early by sonication or DNase action. Comparison of the data obtained for different tissues shows an inverse correlation between the amounts of chromosomal HMG1 and 2, on the one hand, and of histone H1(0), on the other hand. These results suggest that chromosomal HMG1 and 2 take part in the processes that occur during cell differentiation, while histone H1(0) is induced to preserve differentiated cells from dedifferentiation. PMID- 2583186 TI - The activity of GD3 synthase modulates the ganglioside pattern in rat liver. AB - Variations of the ganglioside composition in the livers of Wistar rats correlated with the activity of GD3 synthase in the corresponding liver homogenates. With increasing enzyme activity, higher proportions of b-series gangliosides (GD3, GD1b, GT1b) were detected. No significant changes in the activity of GM2 synthase or GM1 synthase were observed, indicating a regulatory function for GD3 synthase in this tissue. Young animals showed an average GD3 synthase activity of 0.5-0.6 nmol.h-1.mg protein-1 without sex-dependent variations. Among the older animals, however, males expressed an activity five-fold higher than females, suggesting that this enzyme might be affected by hormones. PMID- 2583188 TI - A new probe for affinity labelling pancreatic cholecystokinin receptor with minor modification of its structure. AB - Biochemical studies on receptors for peptides are most often carried out on affinity-labelled (peptide-receptor) complexes. Necessarily, the assumption is made that a covalent (peptide-receptor) complex behaves as the native receptor. The validity of this assumption is dependent on both the affinity-labelling technique and the resolution of the analytical method used for biochemical characterization. We designed a new affinity-labelling probe in order to minimize structural modifications occurring within the affinity-labelled cholecystokinin (CCK) receptor protein. The probe was 125I-labelled 2-(p-azidosalicylamido)-1,3 dithiopropionate-[Thr28,Ahx31 ]CCK-25-33, (125I-ASD-[Thr28,Ahx31]CCK-25-33), the peptide moiety of which was released from its binding site by reduction. It was obtained by coupling a photoactivable chemical to [Thr28,Ahx31]CCK-25-33 via its N-terminus. The resulting peptide was HPLC purified and radioiodinated in the presence of chloramine T. Binding of 125I-ASD-[Thr28,Ahx31]CCK-25-33 was time- and temperature-dependent and reversible. At 25 degrees C, a steady-state level was reached after 60 min and half-maximal dissociation after 38 min. Binding was inhibited by [Thr28,Ahx31]CCK-25-33 and L-364-718 antagonist with IC50 0.4 nM and 0.9 nM, respectively. Photoaffinity labelling of pancreatic plasma membranes by 125I-ASD-[Thr28,Ahx31]CCK-25-33 identified a glycoprotein of Mr 85,000-100,000 which was retained on immobilized wheat germ agglutinin. Enzyme cleavage by endoproteinase Glu-C generated a main fragment of Mr 30,000-34,000. The same glycoprotein was photoaffinity labelled with 125I-DTyr-Gly [Ahx28,31,pNO2Phe33]CCK-26-33 (Ahx, 2-aminohexanoic acid; pNO2Phe,p nitrophenylalanine) an intrinsic probe having its photolabile group sited in the binding domain of cholecystokinin. 125I-ASD-[Thr28,Ahx31]CCK-25-33 is a potentially powerful tool for biologically and biochemically studying cholecystokinin receptors. PMID- 2583187 TI - The 23S ribosomal RNA higher-order structure of Pseudomonas cepacia and other prokaryotes. AB - A 23S ribosomal RNA gene of Pseudomonas cepacia has been cloned and sequenced. A general higher-order structure model based on earlier published models has been derived from comparative analysis of 23S-like rRNAs of eubacteria, archaebacteria, organelles and eukaryotes. Differences between the previous models were carefully analyzed and controversial regions evaluated. Moderately large insertions and deletions have been found at new points in the secondary structure. The analysis of 50 published as well as unpublished 23S rRNA sequences provide additional proof for six of the seven previously suggested tertiary interactions within the 23S rRNA. P. cepacia is the first representative of the beta subgroup of the Proteobacteria phylum whose 23S rRNA has been sequenced. A tree reflecting evolutionary relationships of prokaryotes was constructed. The topology of this tree is in good agreement with the 16S rRNA tree. PMID- 2583189 TI - Purification and characterization of angiotensin-binding protein from porcine liver cytosolic fraction. AB - A protein that binds angiotensins with high affinity was found in porcine liver cytosol, purified to apparent homogeneity and characterized. The protein was named soluble angiotensin-binding protein (sABP) to distinguish it from angiotensin II receptors present on plasma membranes. Purification of the protein was achieved by a combination of ammonium sulfate fractionation, hydrophobic chromatography, ion-exchange chromatography, hydroxylapatite column chromatography and Mono Q ion-exchange chromatography. Specific angiotensin binding activity, as measured using 125I-angiotensin II, was enriched more than 3400-fold. SDS/polyacrylamide gel electrophoresis of the purified sABP yielded a single 75-kDa protein band, in good agreement with the molecular mass estimated by affinity labeling. sABP was very similar to the angiotensin II receptor in its sensitivity to reducing agents and in its affinities for angiotensin analogues ([Sar1, Ala8]angiotensin II greater than angiotensin III greater than angiotensin II greater than angiotensin I), suggesting a possible similarity between the ligand-binding sites of sABP and the angiotensin II receptor. To obtain a clue to its physiological role(s), we examined the tissue distribution of sABP and found that this protein is widely distributed not only in the peripheral organs but also in the brain. PMID- 2583190 TI - Ligand-induced conformational changes of citrate synthase studied with the fluorescent probe 8-anilinonaphthalene 1-sulfonate. AB - Experiments are presented which show that oxaloacetate and analogs thereof with (R)-malate substructure, on interaction with citrate synthase linked to synthase 8-anilinonaphthalene 1-sulfonate (ANS), induce identical conformational changes of a characteristic magnitude. A conformational change of lower magnitude is also produced on binding of CoASH or ATP to citrate synthase.ANS and is completed on addition of oxaloacetate. The significance of these ligand-dependent conformational changes is discussed. PMID- 2583191 TI - Interleukin 2 stimulates tyrosine phosphorylation in T cell membrane fractions. AB - Interleukin 2 is a growth factor secreted by T lymphocytes upon antigenic stimulation and inducing the proliferation of T cells bearing at their surface the heterodimeric high-affinity form of its receptor. No enzymatic function has so far been demonstrated in the receptor subunits. In an attempt to elucidate the biochemical pathway of signal transduction, we investigated the capacity of interleukin 2 to modulate tyrosine phosphorylation in T cell membranes. Membrane rich fractions from T cells were tested for their ability to phosphorylate tyrosine in the presence or absence of added recombinant interleukin 2. Using as substrate a synthetic polymer of glutamic acid and tyrosine, we demonstrated a 3 4-fold stimulation of tyrosine phosphorylation in the presence of interleukin 2; this stimulating effect appeared to be well correlated with interleukin 2 function since (a) it was not observed in insensitive cells, (b) it required the presence of the high-affinity form of the receptor and (c) it was dose-dependent. Confirmatory results were obtained by phosphorylating membrane-rich fractions with [gamma-32P]ATP and by analysing the resulting phosphoproteins: only in fractions from cells with the high-affinity form of the receptor were several membrane proteins specifically phosphorylated on tyrosine residues in response to interleukin 2. At least two proteins of 115 and 58 kDa were consistently hyperphosphorylated on tyrosine in an interleukin-2-dependent manner. This stimulation was strongly dependent on the presence of the protein tyrosine phosphatase inhibitor, sodium orthovanadate. Thus, we propose that interleukin 2 enhances tyrosine phosphorylation by stimulating a tyrosine kinase activity. The nature of the enzyme involved remains to be determined. PMID- 2583192 TI - Assessment of the scatter fraction evaluation methodology using Monte Carlo simulation techniques. AB - To evaluate scatter fraction and scatter pair spatial distribution, experimental methods are generally used. These methods make use of a line source, placed along the FOV axis, inserted in a cylindrical phantom filled with air or water. The accuracy of these experimental methodologies can be tested by the use of a Monte Carlo method. In fact, the simulation allows the shape of the scatter event projection and the scatter fraction to be defined. An example of this application is the simulation package PETSI (PET SImulation). In this paper the comparison between the predicted scatter fraction and the experimentally evaluated one, obtained using an ECAT III PT 911/02 double ring whole body scanner are presented. PETSI permits additional data to be obtained: a) the true and scatter component of the energy spectrum; b) the spatial distribution, in the FOV plane, of the detected scatter events at different energy thresholds; c) the scatter to total detected events ratio; d) the predicted scatter fraction at both energy thresholds and FOV diameters. This information is very useful for optimizing both energy threshold and FOV size and to improve the accuracy of the currently used methods for the scatter fraction evaluation. Preliminary results of the predicted scatter fraction in a uniform phantom are presented. PMID- 2583193 TI - A computerized adjustable brain atlas. AB - A computerized brain atlas, adjustable to the patients anatomy, has been developed. It is primarily intended for use in positron emission tomography, but may also be employed in other fields utilizing neuro imaging, such as stereotactic surgery, transmission computerized tomography (CT) and magnetic resonance imaging (MRI). The atlas is based on anatomical information obtained from a digitized cryosectioned brain. It can be adjusted to fit a wide range of images from individual brains with normal anatomy. The corresponding transformation is chosen so that the modified atlas agrees with a set of CT or NMR images of the patient. The computerized atlas can be used to improve the quantification and evaluation of PET data by: Aiding and improving the selection of regions of interests. Facilitating comparisons of functional image data from different individuals or groups of individuals. Facilitating the comparison of different examinations of the same patient, thus reducing the need of reproducible fixation systems. Providing external a priori anatomical information to be used in the image reconstruction. Improving the attenuation and scatter corrections. Aiding in selecting a suitable patient orientation during the PET study. By applying the inverse atlas transformation to PET data set it is possible to relate the PET information to the anatomy of the reference atlas. Thus reformatted PET data from different patients can be averaged, and averages from different categories of patients can be compared. This procedure will facilitate the identification of statistically significant differences in the PET information from different groups of patients. PMID- 2583194 TI - A new approach to positron emission tomography. AB - A recently developed detection principle for gamma rays offers the prospect of improving the performance of positron emission tomographic scanners. This detection principle is based on the use of BaF2 scintillator and photosensitive wire chambers. We present technical results obtained with a prototype detector. It is shown that the impact point of the gamma ray can be determined with a precision of a few mm and that the detection efficiency is 60% with a time resolution of 10 ns (FWHM). A scanner based on the new principle is described and its anticipated performance discussed. PMID- 2583195 TI - Image quantification with a large area multiwire proportional chamber positron camera (MUP-PET). AB - A large area multi wire proportional chamber positron camera system is under evaluation for clinical Nuclear Medicine investigation using isotopes both from the house generators (68Ga) and from remote cyclotrons (18F, 124I, 64Cu and 81Rb). Images are reconstructed using a fully three dimensional (3D) algorithm and exhibit equal resolution in all three orthogonal directions. The axial field of view of 15 cm is large enough to allow coverage of the whole brain. This paper discusses the performance of the MUP-PET system with particular emphasis on quantification and the development of an attenuation correction scheme for a large area detector system. The distribution of scattered and accidental events is investigated and observed to contribute a fairly uniform background to the image. Dead time correction factors are calculated from an analytical expression obtained by considering the various sources of dead time present in the system. Following correction for attenuation, accidentals, scattered events and dead time, reconstructed phantom images show a strong linear correlation (r = 0.998) between count density and regional isotope concentration. The extension of the methods to clinical studies is discussed. PMID- 2583196 TI - Influence of some instrumental parameters on the determination of quantitative data using the PET scanner PC4096-15WB. AB - In order to evaluate the influence of physical and instrumental limitations of the PET technique on metabolic data, various parameters have been tested. The measurements were done with a whole body PET scanner PC4096-15WB. The dependence on the transaxial resolution of reconstruction filter cut off frequency alpha c was investigated. The high resolution (4.8 mm at r = 0 in the field of view) and the low scatter fraction (less than 5%) of this system yields a higher grey/white matter ratio (3.8:1) than that found with older scanners (2:1). The use of a rotating pin source allows transmission scans to be performed after tracer administration with an error of less than 5%. PMID- 2583197 TI - Evaluation of PET count rate performance. AB - A proposal is made for the test conditions to evaluate PET count rate performance. This performance depends in a complex manner on the spatial distribution of activity and scattering material. Therefore, a combined body phantom is proposed, which is as simple as possible but which adequately simulates the range of clinical application of a whole body tomograph. Taking into account the special properties of the new block detector design, a comprehensive test procedure is developed. This includes not only the common count rate characteristic, but also checks for the accuracy of randoms estimation and count loss correction schemes, and for the occurrence of pulse pile up. This is done for different source and scatter configurations, simulating brain, cardiac, and abdominal imaging, respectively. Examples are given, based on measurements of the latest generation PET scanners, namely the CT1 PT 931/08-12 and the Scanditronix PC 2048-07WB. PMID- 2583199 TI - A preliminary evaluation of the Scanditronix PC2048-15B brain scanner. AB - The PC2048-15B is the brain version of the new generation of Scanditronix positron camera systems. It is based on a detection unit with 16 scintillating crystals mounted on 2 dual photomultiplier tubes. A system description is given and preliminary test results including spatial resolution, sensitivity to true and random coincidences, scatter correction, and count rate linearity are presented. PMID- 2583198 TI - Online brain attenuation correction in PET: towards a fully automated data handling in a clinical environment. AB - We have improved the calculation of the brain attenuation correction in positron emission tomography (PET) and set up a procedure which allows the clinician to get a fully corrected image in a single reconstruction step, without human intervention. By using a general object description scheme based on polygonal contour trees we are able to calculate the attenuation correction for brain tissue, bone and head holder. The head contour is generated from the emission sinogram. On a set of 15 adult patients, the emission values obtained using this calculated attenuation compare favorably with those obtained with an attenuation resulting from a transmission measurement. Residual discrepancies are attributed to incomplete scatter compensation between emission and transmission. The robustness of the algorithm has been tested on more than 100 brain fluorodeoxyglucose (18FDG) studies in adult patients, including pathological cases. Its applicability for 18FDG studies in children and for other tracers such as water (H2 15O) and fluoroethylspiperone (18FESP) is also presented. PMID- 2583200 TI - Measured attenuation correction methods. AB - Accurate attenuation correction is a prerequisite for the determination of exact local radioactivity concentrations in positron emission tomography. Attenuation correction factors range from 4-5 in brain studies to 50-100 in whole body measurements. This report gives an overview of the different methods of determining the attenuation correction factors by transmission measurements using an external positron emitting source. The long-lived generator nuclide 68Ge/68Ga is commonly used for this purpose. The additional patient dose from the transmission source is usually a small fraction of the dose due to the subsequent emission measurement. Ring-shaped transmission sources as well as rotating point or line sources are employed in modern positron tomographs. By masking a rotating line or point source, random and scattered events in the transmission scans can be effectively suppressed. The problems of measured attenuation correction are discussed: transmission/emission mismatch, random and scattered event contamination, counting statistics, transmission/emission scatter compensation, transmission scan after administration of activity to the patient. By using a double masking technique simultaneous emission and transmission scans become feasible. PMID- 2583201 TI - Scatter fraction: measurement and correction. AB - The concept of scatter in Positron Emission Tomography is reviewed regarding origin and influence on data. Different ways to measure and correct for scatter are discussed. PMID- 2583202 TI - Study on the stability of the calibration and normalization in PET and the influence of drifts on the accuracy of quantification. AB - With regard to the quality control of quantification in positron emission tomography some characteristics were examined, to develop a simple method for frequent monitoring. The stability and uniformity of the detector count rate was checked by plotting the RMS deviation of the non normalized count rate and the standard deviation of the normalized count rate, each normalized to its value after the calibration or normalization respectively. Switching off a single detector did not impair the image quality, but the normalized image pixel counts were reduced by 2%-3% when a detector block was switched off. Thus in case of need, a weak detector can still be used to perform a scan. A reduced count rate capability at specific activities above 5 x 10(4) Bq/ml (approximately 1.5 x 10(5) corrected true system counts/s or approximately 1.5 x 10(4)/s for a plane) was found compared to the maximum usable activity of 8 x 10(4) Bq/ml obtained 1 year earlier, indicating a drift in the count loss corrections. A variation of the room temperature changes the temperature distribution inside the gantry by 5% per degree C and the drift of the sensitivity (normalized image pixel counts) is 2% per degree C. PMID- 2583203 TI - Quality control procedures in positron tomography. AB - The derivation of physiological parameters in positron tomography relies on accurate calibration of the tomograph. Normally, the calibration relates image pixel count density to the count rate from an external blood counter per unit activity concentration in each device. The quality control of the latter is simple and relies on detector stability assessed by measurement of a standard source of similar geometry to a blood sample. The quality control of the tomographic data depends on (i) detector stability, (ii) uniformity of calibration and normalisation sources and (iii) reproducibility of the attenuation correction procedure. A quality control procedure has been developed for an 8 detector ring (15 transaxial plane) tomograph in which detector response is assessed by acquiring data from retractable transmission ring sources. These are scanned daily and a print out of detector efficiencies is produced as well as changes from a given date. This provides the raw data from which decisions on recalibration or renormalization are made. PMID- 2583204 TI - Aspects of three dimensional reconstruction for a multi ring positron tomograph. AB - An important feature of multi ring positron tomographs is the inter plane septa, the purpose of which is to reduce random and scattered coincidences. In general, such septa also eliminate the coincidence lines of response between pairs of detectors more than one ring apart. The operation of a camera without septa must result in an increase not only in the true coincidence rate, but also in the singles, and therefore in the dead time and randoms rate, and in the scattered coincidences. A configuration option in the coincidence hardware of the 8 ring, 15 slice ECAT 931/08-12 enables a full set of 64 sinograms to be acquired when the septa are removed. The detector normalisation and transmission data for studies with the septa out can be obtained using a rotating pin source. To take maximum advantage of the additional signal, the emission data must be reconstructed using a fully three dimensional reconstruction algorithm. This paper presents an analysis of some phantom studies acquired without septa and reconstructed in three dimensions. The results are compared with data acquired with septa for the same phantoms imaged under similar conditions. It is found that, with the septa removed, the signal to noise for a uniform, 20 cm diameter cylinder improves by a factor of 2.8 in the centre of the field of view, whereas in regions distant from the centre in the axial direction, the signal to noise decreases due to the increase in scatter and randoms. An improvement in signal to noise is observed in 6 cm of the 10 cm axial length of the tomograph. PMID- 2583206 TI - Measurement of resolution and recovery in recent generation positron tomographs. AB - In positron tomographic images, the ability to differentiate closely lying structures, the spillover of activity from a region into adjacent regions and the reduction in apparent isotope concentration in small structures are all dependent on spatial resolution. Resolution in the reconstructed image is affected by (i) detector size, (ii) the spatial sampling used (e.g. stationary, wobble), (iii) the amount of smoothing in the reconstruction process (or subsequent to reconstruction) and (iv) the image pixel size. Under ideal conditions, modern commercial tomographs can produce a reconstructed spatial resolution of 5 mm or less. However, this is rarely realizable in a clinical study due to the inadequacy of counting statistics and the amplification of statistical noise. In practice, a smoother filter has to be used. This paper presents a summary of practical measurements of spatial resolution, and the related count recovery, performed on recent generation positron tomographs. It is intended to contribute to the definition of methods of measuring these parameters which is part of an on going concerted action in positron tomography supported by the European Commission. PMID- 2583205 TI - Evaluation of the significance of "redistribution" in I-123 IMP SPECT in cerebrovascular disorders--a comparative study with PET. AB - We evaluated the significance of redistribution in 123I-IMP SPECT study using PET. Twelve lesions in ten patients were selected. These lesions were classified into the following three groups; ischemia, infarction of subacute phase and infarction of chronic phase. All lesions with ischemia or subacute infarction showed good or moderate redistribution. Three of four lesions with chronic infarction showed no redistribution. The mean values of rCBF and rCMRO2 were highest in the lesions with good redistribution, but there was no differences in rOEF with the degree of redistribution. In conclusion, the tissue with good redistribution is not always viable and it was impossible to predict a region with increased rOEF by redistribution alone. PMID- 2583207 TI - Sensitivity and cross calibration. AB - In Positron Emission Tomography it is possible to obtain quantitative information on the distribution of positron emitting radiopharmaceuticals. The different components influencing the sensitivity and the cross calibration of PET systems are discussed especially with respect to the quantitative nature of the PET technique. PMID- 2583208 TI - Diagnosis of heterotopic bone marrow in the mediastinum using 52Fe and positron emission tomography. AB - A patient with hereditary spherocytosis was admitted with mediastinal masses on the chest X-ray. 52Fe and positron emission tomography (PET) showed uptake of 52Fe in the masses and established the diagnosis of thoracic extramedullary hematopoiesis. PMID- 2583209 TI - PET and MR imaging in a neuro-Behcet syndrome. AB - Positron emission tomography (PET) and magnetic resonance imaging (MRI) studies were performed on a case of neuro-Behcet's syndrome. In accordance with the clinical signs, FDG PET (using 18F-labeled 2-F-2'-desoxyglucose) revealed disseminated storage defects in the cerebrum and cerebellum. Focal regions of enhanced signal intensity were demonstrated in the parietal white matter of the cerebrum in T2-weighted images and in the brain stem by MRI. PMID- 2583211 TI - The magnitude of the Mueller-Lyer illusion as a function of hue, saturation, fundus pigmentation, and simulated aging. AB - Ninety-six female college students were tested to determine the effects of hue, saturation, fundus pigmentation, and simulated aging on the magnitude of the Muller-Lyer illusion. In the first experiment, main effects for hue and saturation as well as an interaction effect between them were found to be significant. In the second experiment, filters served to simulate receptor aging by decreasing the visual sensitivity of young adults. A significant main effect of hue and an interaction effect between hue and saturation were found. However, there was no significant effect for fundus pigmentation in either experiment. Comparative analysis of the two experiments showed that only the magnitude of the illusion produced by an unsaturated blue figure decreased significantly when viewed through aging-simulation filters. PMID- 2583210 TI - Changes in the performance of parkinsonian patients and normal aged on the Benton Visual Retention Test. AB - Performance on the Benton Visual Retention Test was compared between those with Parkinson's disease (PD) and age-equivalent controls. The major difference between groups was that those with PD showed an increase in figural reproduction errors between test periods spaced six months apart, while controls showed little increase in errors over this time and made fewer errors at each time of testing. Age and IQ accounted for major proportions of variance in performance for both groups (about 50%), far more than that attributable to group membership. Within the PD group, however, age and disease onset were confounded (r = .92), indicating that age as a variable is quite when disease onset is considered. The results support the notion that PD is associated with change in visual-spatial memory, beyond that predicted by age per se. PMID- 2583212 TI - Simulated aged performance on the embedded figures test. AB - According to Labouvie-Vief (1985) the predominant explanatory mechanism for performance decline among the elderly incorporates a regression-oriented view of cognitive development: The present study tested the hypothesis that age-related performance decline may be explained by the quantitative changes in lower-level visual functions, such as those due to preretinal aging, which preclude the expression of intact cognitive (qualitative) processes. Thirty undergraduate female volunteers (18 to 25 years) viewed the Embedded Figures Test (EFT) under three conditions: no-filter viewing, .6 neutral-density filter viewing, and simulated-aged (yellow-filter plus .5 neutral-density filter) viewing. A one-way ANOVA revealed significant viewing condition effects for the number of items solved, the number of errors, and time-to-solution. Significant linear trends were found for levels of luminous transmittance. Results supported the hypothesis that preretinal aging appears to degrade EFT performance. PMID- 2583213 TI - Physostigmine-induced analgesia in young, middle-aged, and senescent rats. AB - To investigate the effect of aging on cholinergically medicated analgesia, rats from three age groups (3-month, 17-month, and 25-month) were injected with physostigmine (0.0156, 0.0625, or 0.25 mg/kg) or saline. Following the injection, tail-flick latencies were measured at 5-minute intervals for 30 minutes and at 45, 60, 75 and 90 minutes. The analysis of the tail-flick latencies revealed that physostigmine produced a dose-dependent analgesia in all age groups. However, the 17- and 25-month-old age groups were more sensitive to the highest dose of physostigmine. The age-related differences in the analgesia produced by physostigmine is in agreement with other research which has demonstrated that pharmacological stimulation of the cholinergic system produces an equivalent or increased responsivity in aged animals. PMID- 2583214 TI - Attitudes towards aging and physical health. AB - Brief narrative descriptions of four hypothetical individuals who differed in age and physical health were developed and presented to people who differed in age and sex. Each participant read only one of the four profiles. After reading the profile, the participant rated the profiled individual on the Rosencrantz and McNevin (1969) semantic differential scale of attitudes towards aging. Respondents were divided into a young group (29 years or younger), a middle-aged group (30-49 years), and an old group (50 years and older). No participant gender effects were found. All three age groups rated the older and younger profiles of persons in poor health more negatively than those describing healthy persons on each of the three dimensions of the Rosencrantz-McNeven scale. Older respondents tended to view the younger healthy profile and to a lessor extent the younger sick profile more positively than the older profiles, but the young and middle aged respondents viewed the older profiles more positively than the younger profiles on all three dimensions of the scale. These findings suggest that (a) a major component of negative attitudes toward the aged may be related to the more likely occurrence of physical illness in this age group, and (b) more negative attitudes toward the aged are more likely to occur in older than younger respondents regardless of health status. PMID- 2583215 TI - Auditory memory and age-related differences in two-tone frequency discrimination: trace decay and interference. AB - We investigated age-related differences in the time course of two-tone frequency discrimination. Healthy young and elderly adults with normal hearing acuity in the 500-2000 Hz range performed a two-alternative forced choice frequency discrimination task. The stimuli were short tones separated by either a 250-ms (short), 850-ms (medium), or 3000-ms (long) silent inter-interstimulus interval (ISI). Frequency discrimination thresholds were estimated using an adaptive staircase procedure. Although young listeners performed better than the elderly at all ISIs, the latter showed a dramatic elevation of discrimination thresholds at 250 ms, while the thresholds of the young subjects increased significantly at 3000 ms. These results suggest that the elderly may be especially vulnerable to the effects of masking produced by the second tone at the short interval, whereas the young listeners tend to be differentially affected by the trace decay at long ISI. The results are discussed in the framework of stimulus persistence hypothesis. PMID- 2583217 TI - Aging but not arousal influences the effect of environmental noise on the span of attention. AB - In young samples environmental noise acts to reduce attention to low salience events. We asked whether noise would affect old individuals similarly. Furthermore, both aging and noise effects on performance have been attributed to changes in physiological arousal. Therefore, we also asked whether performance changes with noise and aging were necessarily associated with changes in physiological arousal. Young, middle-aged and older individuals (total N = 50) performed a dual task in the presence or absence of 90 dBA white noise. In noise relative to quiet, young and middle-aged but not older participants responded to low salience events less accurately. Neither self-report nor cardiovascular change unequivocally supported the view that general arousal induced the performance changes associated with noise or aging. Cardiovascular changes were controlled by engagement in the task, not by the presence or absence of noise. Age-related changes in preparation for infrequent events were related to vascular change. Alternatives to general arousal explanations were considered. PMID- 2583216 TI - Changes in cognitive and social functioning of diabetic patients following initiation of insulin infusion therapy. AB - Functional health outcomes resulting from intensive insulin regimens may differ depending upon the age of the diabetic patient. This study tested the hypothesis that health functioning is poorer for younger insulin-dependent diabetic (IDDM) patients following a change to the insulin infusion pump regimen, with progressive improvements occurring in functional health status at higher age levels. Thirty IDDM patients aged 10-47 years were administered health status instruments prior to changing to the new regimen, and again six months later. The instruments assessed physical, cognitive, psychological, and social health functioning. When compared at six months to an age-matched control group on conventional insulin therapy, declines in social activities were found for younger insulin pump patients, with improvements occurring linearly as age increased. Lower performance levels were also found for the younger patients in Conceptual Quotient (CQ), an indicator of cognitive functional status, with progressive improvements with age through the early 30s. However, corresponding declines in function occurred at the oldest age levels. Adaptation to an intensive diabetes regimen appears to be more difficult at younger and older age levels. PMID- 2583218 TI - Generation and elaboration in older adults. AB - This study examined the effects of elaborative processing in older adults using the same technique employed in an earlier study (Hashtroudi, Parker, DeLisi, & Wyatt, 1983) on acute alcohol amnesia. Older and younger adults either generated elaborators or were provided with elaborators. Elaborators were either precise or imprecise. Generation, in particular generation of precise elaborators, was effective in enhancing older subjects' level of recall and reducing age differences in memory. It is suggested that active involvement in elaborative processing enables older adults to take advantage of elaboration. Similarities and differences between memory decrements associated with aging and with alcohol intoxication are discussed. PMID- 2583219 TI - Figural after-effects in kinesthesis: more data on age differences. AB - A cross-sectional study of figural after-effects in kinesthesis on 144 subjects ranging in age from 10 to 87 years was carried out. The procedure was nearly identical to one used by Kohler and Dinnerstein (1947). The data show a significant nonmonotonic age trend of the figural after-effect. There is a decline of the kinesthetic after-effect from the youngest to the 35-50-year-old group, followed by an increase in the 51-66-year-olds, and a decrease from this group to the 67-87-year-old group. The pre-test judgments follow a quadratic trend, with a minimal deviation from the objective block size in the group of 35 50-year-old people. The theoretical basis for the relationship between age and figural after-effects is discussed with respect to an age specificity of the attentional capacity, of the cognitive strategy for making successive comparisons, and of stimulus persistence. PMID- 2583220 TI - Aging-related changes in the processing and retention of script information. AB - Adult age differences in the processing of script-related information were examined in two separate experiments. In both studies, no age differences were observed in the pattern of reading times across different types of script actions, with all groups reading relevant actions faster than irrelevant ones. In addition, script structure had similar effects across age groups on both recall and recognition performance, with relevant actions being recalled better than irrelevant ones, and atypical actions recognized better than typical ones. In both cases, however, the younger adults exhibited better memory than the older adults for all types of actions, but the age differences in performance decreased as the relevance and typicality of the target information increased. It is suggested that aging is associated with greater dependence upon scripts in the encoding of scripted events. PMID- 2583221 TI - The gene for the T lymphocyte alloantigen, RT6, is not linked to either diabetes or lymphopenia and is not defective in the BB rat. AB - In an outcross between a diabetic BB/H rat and a healthy Long Evans Hooded rat, the segregation of the RT6 gene was studied in the 207 F2 animals to look for linkage with diabetes or lymphopenia. The recessive gene, albino (c), was used as a marker for the RT6 gene because of the close proximity of these two genes on chromosome 1. Though most of the albino F2 rats should have been homozygous for the BB RT6 gene, we found no increase in the incidence of diabetes or lymphopenia among them when compared to their hooded littermates. Therefore, the RT6 gene was not linked to diabetes or lymphopenia in the BB rat. Moreover, the non lymphopenic albino rats displayed normal RT6 expression when compared to the normal hooded rats showing that the RT6 gene from the BB/H grandfather was not defective. Any alteration in lymphocyte composition which could be specifically related to diabetes was studied by measuring all F2 rats for the major lymphocyte subsets including the RT6+ subset. We found that the typical pattern of lymphopenia described in diabetic BB rats was displayed by both diabetic and non diabetic lymphopenic rats in the F2 generation. Thus, all these lymphocyte abnormalities including the depletion in RT6+ T lymphocytes appeared as a consequence of lymphopenia alone and could not be specifically related to diabetes. PMID- 2583222 TI - Activation of human T cells by toxic shock syndrome toxin-1: the toxin-binding structures expressed on human lymphoid cells acting as accessory cells are HLA class II molecules. AB - Toxic shock syndrome toxin-1 (TSST-1)-binding assay using 125I-labeled TSST-1 showed the presence of specific TSST-1 binding in a B cell fraction of human peripheral blood mononuclear cells and L cells transfected with DR2 genes or DR4 genes but not in a T cell fraction and control L cells. Fixation with paraformaldehyde, an inhibitor of antigen processing, did not remove TSST-1 binding activity of the transfectants. Binding of 125I-labeled TSST-1 to the transfectants was reduced by an anti-DR monoclonal antibody. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the presence of a single band with TSST-1-binding activity and the same migration pattern as DR heterodimers. TSST-1-induced T cell responses, proliferation and interleukin 2 (IL2) production were observed in the presence of the transfectants but not in the presence of control L cells, while concanavalin A-induced IL2 production was observed in the presence of either the transfectants or control L cells. Presence of an anti-DR monoclonal antibody inhibited the TSST-1-induced responses. Paraformaldehyde fixed Daudi cells were effective in supporting TSST-1-induced IL2 production by T cells. These results indicate that HLA class II molecules directly bind intact TSST-1 and perform an essential role as the TSST-1-binding structures on accessory cells in T cell activation by the toxin. PMID- 2583223 TI - B cell repertoire in adult antigen-free and conventional neonatal BALB/c mice. II. Analysis of antigen-binding capacities in relation to VH gene usage. AB - Hybridomas were derived from lipopolysaccharide-reactive splenic B cells of adult germ-free BALB/c mice fed a chemically defined ultrafiltered "antigen-free" diet (GF-CD) and from splenic B cells of 5-day-old conventional (CV-NEO) BALB/c mice. The monoclonal antibodies (mAb) from both collections of hybridomas were tested for reactivity against a large panel of antigens of exogenous and endogenous origin. As a source of natural exogenous antigens 36 different bacteria and 9 different viruses were used, while as endogenous antigens frozen tissue sections of stomach, liver and kidney, the Hep-2 cell line and the anti-idiotopic mAb Ac38 and Ac146 were used. In both collections of mAb approximately 70% reacted with one or more bacterial antigens, while no reactivity could be detected against the viral antigens. Of the GF-CD and CV-NEO hybridomas, 16% and 19%, respectively, reacted with one or more frozen tissue sections. Overall 56% and 68% of the GF-CD and CV-NEO hybridomas, respectively, were producing multireactive antibodies reactive to several exogenous and/or endogenous antigens. Among the GF-CD hybridomas a correlation was found between multireactivity and the usage of the VH gene family PC7183. In CV-NEO hybridomas, however, the preferential utilization of the VH gene family PC7183 was found among both mono- and multireactive hybridomas. The results suggest (a) that the actual B cell repertoire of neonatal mice consists of a large proportion of multireactive B cells which are reactive with autoantigens and bacterial antigens, but not viral antigens and (b) that in antigen-deprived mice the neonatal repertoire is largely preserved during maturation of the mice. PMID- 2583224 TI - Detection of soluble class I molecules (non HLA-A or HLA-B) in serum, spleen membranes and lymphocytes in culture. AB - Soluble major histocompatibility complex class I molecules (sHLA) present in human serum can be resolved by gel filtration into two different peaks with an apparent molecular mass of about 200 kDa (30% of the total) and 50-60 kDa (60% 70%). The serological analysis of the peaks shows that A or B specificities can only be detected in the 200 kDa peak while both are recognized by the monomorphic W6/32 monoclonal antibody (mAb) and anti-beta 2-microglobulin mAb. Such sHLA (non HLA-A or -B) molecules are released from human spleen membranes upon incubation at 37 degrees C and have been purified by affinity chromatography with mAb W6/32 bound to Sepharose. The molecular mass analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis of the sHLA (non HLA-A or -B) and of the classical HLA-A or -B antigens still bound to the membranes and purified from the same membranes after detergent solubilization does not show a significant difference, indicating that sHLA do not represent proteolytic fragments of the classical HLA-A or -B antigens. The presence of sHLA (non HLA-A or -B) has also been detected in the supernatants of lymphocyte cultures and increases dramatically upon stimulation by mitogens. The effect of pokeweed mitogen, phytohemagglutinin, Staphylococcus aureus Cowan strain and phorbol 12-myristate 13-acetate on the secretion of sHLA has been studied. The molecular mass of the secreted sHLA (detected using [14C]leucine) is compared with the classical transmembrane proteins. PMID- 2583225 TI - Only DFL16, DSP2, and DQ52 gene families exist in mouse immunoglobulin heavy chain diversity gene loci, of which DFL16 and DSP2 originate from the same primordial DH gene. AB - In mice, 12 germ-line DH genes belonging to three different families (DQ52, DSP2 and DFL16) have been identified. The DH genes other than DQ52 are clustered in the 60 kb-long region located between VH and JH genes. Since there are seven DH gene families (DHQ52, DXP, DA, DK, DN, DM and DLR) in humans, we tried to identify new DH gene families in the 60 kb-long region using human DH gene probes. Mouse and human DH genes showing the highest similarity were mouse DFL16 genes and human DA genes. Southern hybridization of the mouse clones covering the 60-kb region with human DH probes did not detect any other DH genes. Nucleotide sequence analysis of the 4.0-kb fragment containing the DFL16.1 gene confirmed this conclusion. Comparison of the 12 germ-line DH genes and more than 150 somatic DH sequences also indicated that there are not more germ-line DH genes in the mouse genome. Moreover, comparison of nucleotide sequences of DFL16.1 and DSP2.2 genes and their surrounding regions suggests that both DH gene families originate from the same primordial DH gene. Using the flanking sequences of both DH genes, the divergence date between DFL16 and DSP2 genes was estimated at around 37 million years ago. PMID- 2583226 TI - Bioactive human recombinant tumor necrosis factor-alpha: an unstable dimer? AB - As determined by native polyacrylamide gel electrophoresis (PAGE) and gel chromatography the molecular mass of native tumor necrosis factor (TNF)-alpha was approximately 35 kDa. When incubated at low concentrations (less than 1 nM) 125I labeled TNF-alpha and unlabeled TNF-alpha rapidly multimerized or dissociated into monomers and bioactivity decreased. Sodium dodecyl sulfate (SDS)-PAGE analysis of cross-linked 125I-labeled TNF-alpha demonstrated bands of multi- and trimeric TNF-alpha in addition to dominating bands of dimers and monomers. Tri-, di- and monomeric TNF-alpha were recovered from SDS-PAGE gels and allowed to renature. Of the original receptor-binding activity, 10%-15% was obtained with cross-linked TNF-alpha dimers, whereas none was recovered from preparations of trimeric TNF-alpha. Multimeric and monomeric TNF-alpha exhibited little or no binding activity, and cell-bound, cross-linked TNF-alpha which was dissociated from cellular binding sites was mainly dimeric. 125I-labeled TNF-alpha bound to lymphokine-activated killer (LAK) cells and binding kinetics were much similar (Kd approximately 100 pM) to those reported in other normal cell types. The number of receptors per LAK cell was approximately 4 x 10(3). Cross-linking of TNF-alpha to binding sites in U-937 and LAK cells yielded a receptor-ligand complex of about 80/90 kDa. At 37 degrees C, 125I-labeled TNF-alpha was rapidly internalized and degraded in L-929, U-937 and LAK cells. Degradation of ligand and recycling of receptors were blocked in the presence of methylamine. Methylamine significantly inhibited TNF-alpha-mediated cytolysis of L-929 cells and caused a quantitatively corresponding reduction in cellular TNF-alpha uptake, indicating that L-929 lysis was mediated by receptors. PMID- 2583228 TI - A new cell surface molecule closely related to mouse class I transplantation antigens. AB - The "37" H-2 class I mouse gene, located in the Tla complex, is poorly polymorphic and is transcribed in a wide variety of cells and tissues. Using antisera directed against peptides deduced from the gene sequence, we demonstrate that the 37 gene encodes a 45.5-kDa cell surface glycoprotein. This protein, initially identified on the surface of mouse L cells transfected with an overexpressing 37 gene, is present on cells such as splenocytes of various mouse strains except those of A/J mice. Thus, mouse cells may express not only the major transplantation antigens encoded by the K and D region genes, but at least one additional poorly polymorphic class I molecule encoded by the 37 gene. PMID- 2583227 TI - The proliferation and life-span of rat large granular lymphocytes: effects of cytokines. AB - Pulse labeling of large granular lymphocytes (LGL) with [3H]thymidine for 1 h in vitro showed that 1%-7% of LGL were in S phase in the blood, spleen and liver of unstimulated euthymic and athymic rats as scored with autoradiography. Repetitive injections of [3H]thymidine over 2-7 days revealed that about half of the blood and spleen LGL had formed by division of precursors during this week. Stimulation of rats with the interferon inducer poly(I).poly(C) increased the proportion of S phase LGL rapidly and simultaneously in the blood, spleen and liver, so that by 20 h after stimulation ca 30% of LGL were in the S phase in these organs. This LGL proliferation was accompanied by an increased number of LGL in all three compartments 48-96 h after poly(I).poly(C) injection. Blood LGL cultured in cell impermeable diffusion chambers in the peritoneal cavity of poly(I).poly(C) stimulated rats exhibited enhanced natural killer (NK) activity but no proliferative response, indicating that mature LGL were not induced to undergo blastogenesis by poly(I).poly(C) in vivo. Pretreatment of NK cells with rat interferon (IFN-alpha/beta) and with human recombinant interleukin 2 (rIL 2) in vitro, showed that these two cytokines, when combined, had opposing effects on NK activity and proliferation: whereas rIL 2 inhibited the IFN-induced augmentation in NK activity, IFN inhibited the rIL 2-induced LGL proliferation. PMID- 2583229 TI - Major histocompatibility complex-linked and T cell-dependent selection of antibody repertoires. Quantitation of I-E-related specificities in normal mice. AB - Autoreactive B cell repertoires with major histocompatibility complex (MHC) class II (I-E)-related specificities were investigated by quantitating frequencies of specific B lymphocyte clonal precursors in unmanipulated normal and athymic BALB/c mice and in I-E-negative, MHC-congenic BALB.B10 mice. Clonal culture supernatants containing anti-I-E antibodies were identified by their selective binding to I-Ek alpha Ed beta-transfected fibroblasts, and those containing anti anti-I-E antibodies were detected by their selective binding to anti-I-E monoclonal antibodies. Analysis of splenic B lymphocytes from BALB/c mice revealed high frequencies of both specificities in the compartment of large, naturally activated cells, but not among small, resting lymphocytes. The selection of such clones was found to be MHC linked because of their absence in BALB.B10 mice, and T cell dependent because of their reduced frequency in athymic BALB/c mice. The positive selection of V regions representing complementarities and mimicries of self-class II antigens may suggest a set of mechanisms participating in the maintenance of natural tolerance. PMID- 2583230 TI - Sequence and linkage of the V kappa 21A and G germ-line gene segments in the mouse. AB - The germ-line V gene segments encoding the subgroups A and G of the BALB/c V kappa 21 family were cloned and assigned to the previously described 30-kb cluster of the V kappa 21 family. Sequence comparison revealed close homology between the two gene segments at the DNA and the predicted amino acid sequence level, indicating that V kappa 21A and V kappa 21G originated by a rather recent gene duplication. PMID- 2583231 TI - Naloxone-induced facilitation of C-fiber reflexes is reduced by chronic morphine. AB - The effects of chronic morphine on endogenous opioid function were examined in feline spinal cord. Naloxone-induced facilitation (disinhibition) of the C-fiber reflex was used as a model to reflect endogenous opioid function. Facilitation was reduced 24 h after withdrawal of chronic morphine (14 days). Acute morphine failed to depress C-fiber reflexes in the abstinent cats, indicating tolerance. Thus, these results demonstrated that, after chronic morphine, spinal endogenous opioid function was reduced due to tolerance. PMID- 2583232 TI - BRL 34915 (cromakalim) enhances voltage-dependent K+ current in cultured rat hippocampal neurons. AB - The whole cell voltage-clamp recording technique was used to study the effects of the benzopyran antihypertensive agent BRL 34915 on voltage-dependent outward currents in cultured rat hippocampal neurons. Extracellular perfusion with BRL 34915 (10-500 microM) produced a dose-dependent increase in the sustained (minimally inactivating) voltage-dependent outward current without altering the transient outward current (IA) or producing a change in the resting current at 60 mV. One-half maximal facilitation of the sustained outward current occurred at 40 microM and maximal facilitation (59%) at 100 microM. The increase in outward current occurred at all potentials where hippocampal neurons exhibited outward rectification (greater than -30 mV). The effect of BRL 34915 was slow to develop (requiring as long as 5-15 min to achieve maximal effect) and persisted for at least 10-15 min after cessation of the drug superfusion. Like the sustained outward current recorded under control conditions, the outward current augmented by BRL 34915 was inhibited by the K+ channel blocker tetraethylammonium (20 mM). These results indicate that BRL 34915 can enhance the activity of sustained voltage-dependent K+ channels in mammalian CNS neurons. PMID- 2583233 TI - Affinity profiles of hexahydro-sila-difenidol analogues at muscarinic receptor subtypes. AB - In an attempt to assess the structural requirements of hexahydro-sila-difenidol for potency and selectivity, a series of analogues modified in the amino group and the phenyl ring were investigated for their affinity to muscarinic M1-(rabbit vas deferens), M2- (guinea-pig atria) and M3- (guinea-pig ileum) receptors. All compounds were competitive antagonists in the three tissues. Their affinities to the three muscarinic receptor subtypes differed by more than two orders of magnitude and the observed receptor selectivities were not associated with high affinity. The pyrrolidino and hexamethyleneimino analogues, compounds substituted in the phenyl ring with a methoxy group or a chlorine atom as well as p-fluoro hexahydro-difenidol displayed the same affinity profile as the parent compound, hexahydro-sila-difenidol: M1 approximately M3 greater than M2. A different selectivity pattern was observed for p-fluoro-hexahydro-sila-difenidol: M3 greater than M1 greater than M2. This compound exhibited its highest affinity for M3-receptors in guinea-pig ileum (pA2 = 7.84), intermediate affinity for M1 receptors in rabbit vas deferens (pA2 = 6.68) and lowest affinity for the M2 receptors in guinea-pig atria (pA2 = 6.01). This receptor selectivity profile of p-fluoro-hexahydro-sila-difenidol was confirmed in ganglia (M1), atria (M2) and ileum (M3) of the rat. Furthermore, dose ratios obtained with either pirenzepine (M1) or hexahydrosila-difenidol (M2 and M3) and the p-fluoro analogue used in combination suggested that the antagonism was additive, implying mutual competition with a single population of muscarinic receptor subtypes. These results indicate that p-fluoro-hexahydro-sila-difenidol represents a valuable tool for characterization of muscarinic receptor subtypes. PMID- 2583234 TI - Peptides of the corticoliberin superfamily attenuate thermal and neurogenic inflammation in rat pawskin. AB - The paws of pentobarbital-anesthetized rats were immersed in 48 or 58 degree C water for 5 min and the thermal inflammatory response to heat was measured by Evans blue dye leakage into the pawskin. Sauvagine, sucker fish urotensin I and human/rat corticotropin-releasing factor (CRF), homologous peptides belonging to the corticoliberin superfamily, injected i.v. 10 min before heat exposure, inhibited dye leakage with ED50 (nmol/kg) of 0.44, 1.5 and 5.9, respectively. The same rank order of potency was observed when the peptides were tested against the protein extravasation evoked by antidromic stimulation of the rat saphenous nerve. The alpha-helical CRF-(-9-41) antagonist, administered alone at 24 nmol/kg i.v., did not affect the heat-induced dye leakage into skin; but it attenuated the effects of h/rCRF, urotensin I and sauvagine. h/r[Tyr0]CRF, ovine[Nle21,Tyr32]CRF and h/r[Met(O)21,38]CRF, administered 24 nmol/kg i.v., did not affect the dye leakage response to heat. Peptides of the corticoliberin superfamily may have the unusual property of making small blood vessels less permeable when responding to injurious stimuli. PMID- 2583235 TI - Minaprine antagonises the serotonergic inhibitory effect of trifluoromethylphenylpiperazine (TFMPP) on acetylcholine release. AB - The serotonin agonist, m-trifluoromethylphenylpiperazine (TFMPP), inhibited the K+-evoked release of [3H]acetylcholine ([3H]ACh) from rat hippocampal synaptosomes. The inhibitory effect of TFMPP was blocked by the non-selective 5 HT1 antagonist, methiothepin, but was not affected by ketanserin, mesulergine or spiperone. The 5-HT3 antagonist, MDL 72222, slightly reversed the inhibitory effect. The antidepressant, minaprine, did not modify the basal release of [3H]ACh but it antagonised the inhibitory effect of TFMPP on the K+-evoked release. The maximal reversal was found at 0.3 microM minaprine. These results suggest that minaprine interacts with heterologous presynaptic 5-HT1B receptors. A new approach is thus opened to the study of the mechanism of action of antidepressant drugs. PMID- 2583236 TI - Endothelium removal does not affect potentiation by neuropeptide Y in rabbit ear artery. AB - Influence of endothelial cells on the effect of neuropeptide Y (NPY) was investigated. NPY (30 nM) doubled the vasoconstriction elicited by transmural nerve stimulation (8 pulses at 8 Hz) in the perfused rabbit ear artery with or without endothelium. Conditions that increase the biophase concentration of norepinephrine, longer stimulation trains or application of yohimbine, decreased the potentiation by NPY, although in the presence of cocaine potentiation by NPY was unchanged. However, no significant differences between control and endothelium-removed arteries were revealed. Thus modulation of adrenergic neurotransmission by NPY does not depend on endothelium-derived vasoactive substances. PMID- 2583237 TI - Effects of adenosine analogs and ouabain on rhythmicity in human coronary artery. AB - The effects of adenosine receptor agonists and ouabain on rhythmicity were studied in coronary arteries obtained from 12 human donors. Ring segments of left anterior descending coronary arteries were suspended in organ baths for measurement of isometric tension. Prostaglandin F2 alpha (PGF2 alpha:10 microM) produced tonic contractions followed by phasic relaxations. The phasic relaxations were completely abolished by either 100 nM ouabain or 50 mM KCl and changed to tonic contraction. The rhythmicity was also inhibited in K+-free medium. The adenosine analogs, 5'-N-ethylcarbo-xamidoadenosine (NECA) and 2 chloroadenosine (CAD) caused a concentration-dependent relaxation of the maximum force, minimum force, and decreased the frequency of rhythmicity. In rings that did not show phasic activity in response to PGF2 alpha, NECA and CAD produced concentration-dependent relaxation of the tonic contraction. Prior treatment with ouabain (100 nM) prevented the relaxing response of these compounds and the development of rhythmicity. Our data show that PGF2 alpha-induced rhythmicity in human coronary arteries could be inhibited by ouabain, alterations in K+ concentrations and by adenosine analogs. The relaxations produced by adenosine analogs could also be inhibited by ouabain. PMID- 2583238 TI - Evidence for adenosine A2 receptor involvement in the hypomobility effects of adenosine analogues in mice. AB - The hypomobility induced by a series of adenosine analogues was investigated using a holeboard test and their behavioral potencies correlated to their reported adenosine A1 and A2 receptor affinities. All of the adenosine analogues dose dependently inhibited both exploratory behavior (head dipping) and locomotor activity. The rank order of potency 5'-ethylcarboxamido adenosine (NECA) greater than 5'-methylcarboxamido adenosine (MECA) greater than N6-[(R)-1-methyl-2 phenylethyl]adenosine (R-PIA) greater than N6-cyclohexyladenosine (CHA) = N6 cyclopentyladenosine (CPA) greater than N6-[(S)-1-methyl-2-phenylethylladenosine (S-PIA) greater than N6-(2-hydroxyethyl)adenosine (2-OH-ethyl) was observed for inhibiting both activities. The behavioral potency of these adenosine analogues correlates extremely well with their reported A2 receptor affinity (r2 = 0.93, P less than 0.01 and r2 = 0.86, P less than 0.05 for locomotor and head dipping activity respectively), but very poorly with their reported A1 receptor affinity (r2 less than 0.02, P greater than 0.50 for both activities). These results suggest that adenosine A2 receptors, but not A1 receptors, may be involved in the hypomobility induced by adenosine analogues. PMID- 2583239 TI - Alleviation of myocardial dysfunction and abnormal lactate metabolism during coronary stenosis in dogs by ICI 118,551. AB - Hemodynamic parameters, segment shortening in the ischemic myocardium and cardiac lactate extraction were estimated in the presence of a critical coronary stenosis, before and after administration of the selective beta 2-adrenoceptor antagonist, ICI 118,551, or the beta 1-adrenoceptor antagonist, atenolol, to anesthetized dogs. ICI 118,551 (0.2 and 0.5 mg/kg i.v.) and atenolol (0.2 mg/kg i.v.) produced significant decreases in both heart rate (by 6, 14 and 20% of the predrug value, respectively) and maxLVdP/dt (by 15, 26 and 24% of the predrug value, respectively). ICI 118,551 (0.5 mg/kg) and atenolol significantly improved the impaired shortening of the myocardial segment when compared with the change seen after saline administration. ICI 118,551 at both doses and atenolol significantly increased depressed cardiac lactate extraction while saline did not. Increasing heart rate by pacing abolished the beneficial effects of ICI 118,551 and atenolol on ischemic myocardial segment shortening and lactate metabolism. The data suggest that not only beta 1- but also beta 2-adrenoceptor blockade may contribute to the amelioration of myocardial ischemia in a model of coronary stenosis. PMID- 2583240 TI - Effects of lithium ex vivo on the GTP-mediated inhibition of calcium-stimulated adenylate cyclase activity in rat brain. AB - The aim of this study was to investigate the effects of chronic lithium treatment on calcium (Ca2+)-stimulated adenylate cyclase activity in rat striatum and hippocampus, and to elucidate the effect of lithium treatment on the neurotransmitter/GTP-mediated inhibition of Ca2+-stimulated enzyme activity in the two brain areas. Lithium treatment, which gave a serum-lithium concentration of 0.9 +/- 0.16 mmol/l, enhanced Ca2+-stimulated enzyme activity in the hippocampus but reduced this activity in the striatum. Serotonin (5-HT) dose dependently reduced Ca2+-stimulated adenylate cyclase activity in the hippocampus, and chronic lithium administration reduced the ability of 1 microM 5 HT to inhibit Ca2+-stimulated enzyme activity. Furthermore, the 5-HT-induced GTP mediated inhibition of Ca2+-stimulated adenylate cyclase activity in the hippocampus was markedly decreased by lithium. Increasing concentrations of dopamine in the striatum did not, however, affect Ca2+-stimulated adenylate cyclase activity and the inhibition of enzyme activity observed with increasing concentrations of GTP was not influenced by chronic lithium treatment. These results demonstrate that lithium ex vivo exerts dual and region-specific effects on Ca2+-stimulated adenylate cyclase in the brain. Furthermore, long-term administration of lithium could reduce the inhibitory effect of 5-HT on adenylate cyclase in the hippocampus, by influencing the inhibitory GTP-binding protein. The effects of lithium on serotonergic and dopaminergic neurotransmission could be involved in the therapeutic actions of lithium in manic-depressive illness. PMID- 2583241 TI - Association of [3H]zacopride with 5-HT3 binding sites. AB - An assay was developed for [3H]zacopride binding to 5-HT3 specific sites in membranes from rabbit ileum muscularis. The binding was rapid, saturable, reversible, salt-insensitive, unaffected by pH between 6.5 and 9.5, and of high affinity (apparent KD = 0.65 +/- 0.15 nM). ICS 205-930, a potent 5-HT3 antagonist that inhibited competitively, was utilized to define 5-HT3 specific binding. Other 5-HT3 antagonists and agonists, although exhibiting marked differences in potency, were also effective inhibitors; whereas, antagonists of other classes of serotonin receptors, guanyl nucleotides and numerous receptor-specific ligands, including peptide hormones, were inactive. Vagus nerve exhibited the greatest amount of 5-HT3 specific binding amongst rabbit tissues and virtually all of the [3H]zacopride was bound to 5-HT3 binding sites. In rabbit, rat and ferret a fairly uniform distribution of 5-HT3 binding sites was observed along the muscularis of the small bowel. [3H]Zacopride is a high-affinity ligand for detecting 5-HT3 binding sites and rabbit small bowel muscularis membranes are a sensitive system for evaluating the potency of 5-HT3 antagonists or agonists. PMID- 2583242 TI - Characterization of DOI, a putative 5-HT2 receptor agonist in the rat. AB - DOI (1-100 micrograms/kg i.v.) induced an increase in mean blood pressure in the anaesthetized rat. Similarly, in the pithed rat, DOI (1-100 micrograms/kg i.v.) induced a dose-dependent increase in mean blood pressure, as did 5-HT. However, in contrast to 5-HT, DOI did not change the heart rate in either intact or pithed rats. In the pithed rat, the dose-pressor response curves to both 5-HT and DOI were unaffected by MDL 72222 (5-HT3 receptor antagonist), spiroxatrine or (+/-) pindolol (5-HT1A receptor antagonists), idazoxan (alpha 2-adrenoceptor blocking agent) and AR-C 239 (alpha 1-adrenoceptor blocking agent). Only the selective 5 HT2 receptor antagonist. LY 53857, significantly and dose dependently shifted to the right the dose-response curves to both 5-HT and DOI. These results indicated that DOI possesses 5-HT2 agonistic properties and that the pressor response induced by DOI in the pithed rat is mediated via 5-HT2 receptors. PMID- 2583243 TI - The H-L subgroup of guinea-pig cardiac M2 receptors (M2 beta) regulates inositol phosphate formation. AB - In previous studies, we showed that cardiac muscarinic receptors (M2) are composed of two subgroups, M2 alpha and M2 beta, with different affinities for agonists and that the M2 alpha subgroup is coupled with inhibition of adenylate cyclase. We now studied which subgroup was responsible for the formation of inositol mono- (IP), bis- (IP2), tris- (IP3) and tetrakis- (IP4) phosphates in guinea pig heart. Carbachol (1 mM) significantly stimulated the formation of all four IPs in [3H]myoinositol-preloaded slices of guinea-pig ventricles. Acetylcholine (1 mM) also stimulated the formation of IP2, IP3 and IP4. However, oxotremorine (1 mM) only slightly stimulated the formation of IP2, and pilocarpine did not stimulate the formation of any IP. The pED50 values of carbachol for IP2 and IP3 formation were 3.76 and 4.23, respectively, which coincided with the pKd values of the low-affinity agonist binding site (L site) measured by competition of carbachol with [3H]quinuclidinyl benzilate [( 3H]QNB) binding while the pKd value for inhibition of adenylate cyclase coincided with the pKd value of the high-affinity agonist binding site (H site). Treatment of animals with pertussis toxin decreased the formation of IP2 and IP3 by carbachol to 66 and 54%, respectively, but resulted in complete inhibition of adenylate cyclase. These results suggested that muscarinic stimulation of the formation of IPs was manifested through a different receptor subgroup (M2 beta) and GTP binding protein different from those for inhibition of adenylate cyclase. PMID- 2583244 TI - Binding of arylpiperazines to 5-HT3 serotonin receptors: results of a structure affinity study. AB - The binding affinities of a series of arylpiperazine derivatives at [3H]quipazine labeled central 5-HT3 sites were investigated. Features determined to be important for binding include the N4 piperazine nitrogen atom (but not the N1 piperazine nitrogen), and a quinolinyl group. The quinoline nitrogen atom of quipazine also contributes to affinity and its replacement by carbon reduces affinity by 20-fold. The entire quinoline nucleus is not necessary for binding, and certain monocyclic arylpiperazines, particularly those with a chloro group meta to the position of the piperazine ring (e.g. mCPP, MK-212), also bind at 5 HT3, sites; however, the affinities of these agents are at least an order of magnitude less than that of quipazine itself. Taking advantage of the fact that tertiary amines are not well tolerated at 5-HT1B sites, but that N-methyl substituents have little effect on 5-HT3 binding, we designed and synthesized a tertiary amine analog of quipazine, i.e., N-methylquipazine (NMQ). NMQ binds at 5 HT3 sites with an affinity similar to that of quipazine; however, unlike quipazine, NMQ shows very little affinity (IC50 greater than 10,000 nM) for central 5-HT1B sites. PMID- 2583245 TI - Solubilization and characterisation of the cholecystokininB binding site from pig cerebral cortex. AB - Cholecystokinin (CCK) binding sites were solubilized from pig cerebral cortical membranes with digitonin (2%, w/v) in the presence of Na+ (120 mM) and Mg2+ (5 mM). Scatchard plot transformation of equilibrium binding data obtained with 125I CCK-8S gave an apparent dissociation constant (Kd) of 0.6 nM, comparable to that obtained in membranes in the presence of these cations. Hill coefficients close to unity suggested the presence of a single population of receptor sites. Competitive inhibition studies with pentagastrin, gastrin(1-17)S and the CCKA receptor antagonist L-364,718 indicated that the solubilized receptor sites were of the B-type (CCKB), with the same pharmacological profile as that observed in membranes. Optimal specific binding of 125I-CCK-8S to membrane-bound and solubilized receptors was obtained in the presence of divalent cations. Both the membrane-bound and the solubilized receptor activity were attenuated by guanylyl imidodiphosphate (Gpp(NH)p) indicating that the brain CCKB receptors are coupled to G proteins. PMID- 2583246 TI - Estrogen-induced proteins in rat hypothalamus. AB - The identification of estrogen-inducible genes in specific regions of the central nervous system (CNS) will give information about the mechanisms by which this steroid modulates nervous activity. Two-dimensional gel analysis of the proteins synthesized in vitro from mRNA isolated from control or estrogen-treated rats indicated that the levels of mRNA were increased in the estrogen-treated animals. The levels of mRNA were elevated only in those brain regions that express estrogen receptors. PMID- 2583248 TI - Improving the precision of biological age determinations. Part 2: Automatic human tests, age norms and variability. AB - In order to eliminate variability due to test operators, procedures for measuring 12 physiological functions that are candidate biomarkers of aging have been automated. Data was collected from a norm group of 2462 male and female office workers using an instrument which requires no test operators, administers all 12 tests in about 45 min. per subject, computes biological age, prints out results, and stores data on floppy disks for transfer to other computers for analysis. This report a) describes the instrumentation and test procedures, b) presents normal age/sex standards for each of the 12 biomarkers, c) reports the variance of the data for each biomarker by sex, d) lists sources of biomarker variance, e) discusses criteria for biomarker selection and f) examines implications for information loss when biomarker data is combined to calculate biological age. After eliminating chronological age as a variable, the standard deviations of the frequency distributions of predicted age for individual biomarkers were found to vary from .226 to 1.075, a range of more than 4 to 1. Procedures are discussed for improving the ratio of useful-to-useless variance in calculating biological age. PMID- 2583247 TI - Agonist binding to M1 muscarinic receptors is sensitive to guanine nucleotides. AB - Putative M1 (high-affinity pirenzepine) muscarinic receptors in rabbit hippocampal membranes, treated with 0.1 mM N-ethylmaleimide (NEM), were selectively labeled with [3H]pirenzepine. A single class of binding sites was labeled with a Kd of 3.4 nM, consistent with the pharmacologically-defined M1 subtype of muscarinic receptors. While full muscarinic agonists bound to high- and low-affinity states of [3H]pirenzepine-labeled M1 sites with a KL/KH ratio of approximately 100, the ratio for partial muscarinic agonists was approximately 10. The high-affinity binding of all agonists tested required divalent cations, and was interconverted to low-affinity binding in the presence of the non hydrolyzable GTP analogue, guanylyl imidodiphosphate (GppNHp). Direct labeling of the high-affinity agonist state of M1 receptors was achieved with 5 nM [3H]oxotremorine-M by selectively uncoupling the high-affinity agonist state of M2 (low-affinity pirenzepine) receptors with NEM. The rate of dissociation of [3H]Pxotremorine-M from M1 receptors was accelerated 6-fold by GppNHp. These results provide further evidence which suggests that putative M1 muscarinic receptors activate second messenger systems by coupling to NEM-insensitive guanine nucleotide-binding proteins. PMID- 2583249 TI - Glucose metabolism and protein synthesis in stratified squamous epithelia from young and old mice. AB - Glucose metabolism in regionally distinct epidermis and oral epithelia of young adult and aged mice was studied using 5-3H glucose and differentially labelled 14C-glucose. The results obtained with 3H-glucose indicate there is active utilization of glucose by all the epithelia examined. However, an enhanced utilization of glucose was observed in old ear epidermis when compared to that in young mice. The measurements of respiratory 14CO2 in the young and old epidermis indicated that aerobic glycolysis was significantly greater in ear epidermis and buccal epithelium from old than from young mice. Pentose phosphate activity was significantly reduced in palate epithelium from old animals when compared with that of young animals. Incorporation of radioactively labelled leucine and histidine revealed some regional differences between the epithelia examined. However, no age-associated differences were observed in any of the tissues. It is concluded that the observed metabolic changes reflect regionally specific adaptations to local factors rather than representing a programmed biological event. PMID- 2583250 TI - Cholinergic enhancement of megakaryocytopoiesis and granulocytopoiesis in culture: mediation via T-lymphocytes. AB - Addition of carbamylcholine, a cholinergic analogue, to bone marrow cultures enhanced megakaryocytic and granulocytic growth by 60% and 42%, respectively. When carbamylcholine was added to spleen cells cultured in the presence of pokeweed mitogen, the resulting conditioned medium (PWM-SCM) increased the number of megakaryocytic and granulocytic colonies to 159% +/- 6% and 146% +/- 10%, respectively, compared to control cultures stimulated by PWM-SCM alone. To determine if this cholinergic augmentation of colony formation was direct or mediated via accessory marrow cells, cyclosporin A (CyA), a potent T-lymphocyte function inhibitor known to suppress the production of colony-stimulating activity (CSA) by spleen cell cultures, was added to marrow cultures. CyA (3 micrograms/ml) abrogated the enhancement of megakaryocytic and granulocyte macrophage colony growth but had no effect on colony formation when added alone. To confirm the role of T-lymphocytes in the augmented proliferation of megakaryocytopoiesis and granulocytopoiesis, bone marrow cells from T-lymphocyte deficient nude mice were cultured in the presence of carbamylcholine. No significant change was observed in the number of megakaryocyte colony-forming units (CFU-M) and committed granulocyte-macrophage colony-forming units (CFU-C) derived from the marrow of nude mice when cultured in the presence of carbamylcholine. The data suggest that carbamylcholine-induced enhancement of megakaryocytopoiesis and granulocytopoiesis in culture is indirect, requiring a T lymphocyte population. PMID- 2583251 TI - Further studies on the biological activities of the CFU-S inhibitory tetrapeptide AcSDKP. I. The precise point of the cell cycle sensitive to AcSDKP. Studies on the effect of AcSDKP on GM-CFC and on the possible involvement of T-lymphocytes in AcSDKP response. AB - In order to further investigate the mechanisms of spleen colony-forming unit (CFU S) inhibition by the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), the following related subjects were studied: 1) the effects of AcSDKP on the kinetics of granulocyte and macrophage precursor cells (granulocyte-macrophage colony forming cells; GM-CFC); 2) the precise point in the cell cycle of CFU-S that is sensitive to AcSDKP; and 3) the role of lymphocytes in the chain of events leading to the inhibition of CFU-S entry into the cell cycle. The effects of AcSDKP on CFU-S and GM-CFC were tested using the spleen colony assay and methylcellulose culture technique, respectively; the cell cycle kinetic status was determined by the tritiated thymidine suicide technique. Nude mice were studied to assess the role of T-lymphocytes in the inhibitory phenomenon. Our results indicate that: 1) there is no inhibitory effect of AcSDKP on GM-CFC in vitro or in vivo; 2) AcSDKP is active at only the G0 or early G1 phases; and 3) AcSDKP activity is not modulated by T cells. PMID- 2583252 TI - Further studies on the biological activities of the CFU-S inhibitory tetrapeptide AcSDKP. II. Unresponsiveness of isolated adult rat hepatocytes, 3T3, FDC-P2, and K562 cell lines to AcSDKP. Possible involvement of intermediary cell(s) in the mechanism of AcSDKP action. AB - Because the molecular mechanisms of the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP; an inhibitor of spleen colony-forming unit [CFU-S] DNA synthesis) are difficult to study on bone marrow due to the scarcity of CFU-S in this tissue, we sought a pure cell population responsive to the molecule in vitro. Although growth factor-stimulated DNA synthesis in primary culture of hepatocytes and Balb/c 3T3 cells can be inhibited by transforming growth factor beta (TGF beta) and interferon alpha/beta (IFN[alpha/beta], respectively, neither hepatocytes nor 3T3 cells were found to be sensitive to AcSDKP. DNA synthesis in stimulated murine FDC-P2 cell lines and in human K562 cell lines also remained unchanged after exposure to the tetrapeptide. The fact that hepatocytes do respond in vivo to AcSDKP implies the existence of intermediary cell(s) involved in AcSDKP action in vivo that are lacking in hepatocyte culture. Whether intermediary cell(s) are implicated in the inhibitory action of AcSDKP on CFU-S entry into DNA synthesis is now being investigated. PMID- 2583253 TI - The role of interleukin 6 and interleukin 1 in megakaryocyte development. AB - The effect of human interleukin 6 (IL-6) and interleukin 1 (IL-1) on cells of the megakaryocyte lineage from murine bone marrow was examined. In bone marrow liquid culture, IL-6 but not IL-1 increases the amount of acetylcholinesterase, a megakaryocyte marker. In semisolid colony assays, a low level of interleukin 3 (IL-3) was used as a growth factor, and IL-6 and IL-1 were tested for their ability to potentiate the activity of IL-3 to stimulate megakaryocyte colony formation. IL-6 and/or IL-1 had no effect on megakaryocyte colony formation in the absence of IL-3. However, IL-6 was able to stimulate increased megakaryocyte colonies in the presence of IL-3. IL-1 was able to potentiate colony formation only in the presence of both IL-3 and IL-6. PMID- 2583255 TI - Hydrocortisone promotes survival and proliferation of granulocyte-macrophage progenitors via monocytes/macrophages. AB - We have determined the mechanism by which hydrocortisone (Hc) promotes the survival and proliferation of normal human granulocyte-macrophage progenitors (granulocyte-macrophage colony-forming units, CFU-GM). Peripheral blood mononuclear cells were cultured in a liquid system with 0-10.0 microM Hc over 3 weeks. At 7-day intervals 50% of the culture media along with the cells (suspension cells) present in the media were removed and replaced with fresh media. No CFU-GM or very small numbers of CFU-GM were contained in the suspension cells of the 14- and 21-day-old liquid cultures without Hc; CFU-GM were present and increased with increasing concentrations of Hc. The CFU-GM content in suspension cells of 14- and 21-day-old liquid cultures with 1.0 microM Hc was at least threefold higher compared to liquid cultures without Hc. In a double-layer CFU-GM agar culture system, the suspension cells from liquid cultures with 1.0 microM Hc, but not from liquid cultures without Hc, supported CFU-GM proliferation from normal human bone marrow cells. The CFU-GM proliferation inducing ability was confined to the monocytes/macrophages (Mo). CFU-GM colony inhibitory and stimulatory activities were detected in cell-free media recovered from liquid cultures without Hc, but only colony stimulatory activity was detected in the media from cultures with 1.0 microM Hc. These results indicate that greater than or equal to physiological concentrations of Hc (0.1-1.0 microM) are required for the persistence and proliferation of CFU-GM, and the effect of Hc is mediated through the Mo, probably by inhibiting the production of one or more of the CFU-GM colony inhibitory molecules. PMID- 2583254 TI - Normal and malignant human myeloid progenitors differ in their sensitivity to hyperthermia. AB - The effect of in vitro hyperthermia on normal human bone marrow granulocyte macrophage progenitor cells (granulocyte-macrophage colony-forming units, CFU-GM) was compared to its effect on clonogenic acute nonlymphocytic leukemic (ANLL) cells. Mononuclear normal bone marrow cells, blasts from patients with ANLL, and HL-60 cells were incubated at room temperature (control) and at 42 degrees-44 degrees C for 0-120 min prior to assay in methylcellulose. The heat sensitivity of the leukemic cells was significantly greater than that of normal bone marrow progenitors. Two-h exposure to 43 degrees C, for example, resulted in survival of 52% of normal marrow CFU-GM, whereas only 3% of leukemic CFU-GM survived (p less than 0.001 for HL-60 cells and p less than 0.005 for patient blast cells). To determine the effect of hyperthermia on more primitive progenitors and on marrow stromal cells, long-term cultures of normal bone marrow were established using control and heat-treated cells. Generation of CFU-GM was detected in the nonadherent fraction of hyperthermia-treated samples throughout the 5-week culture period. Although stromal development was slightly delayed, hyperthermia treated cells were able to establish stromal layers similar to control cells. These results indicate that normal bone marrow committed progenitor cells are more resistant to hyperthermia than are myeloid leukemic cells. Normal stromal cells and primitive cells assayed in long-term culture are also resistant to hyperthermia that is toxic for leukemic cells. Because of this differential sensitivity to heat, ex vivo hyperthermia may be applicable for removing residual leukemic cells from bone marrow harvested for autologous transplantation. PMID- 2583256 TI - 2'-Deoxycoformycin after failure of alpha-interferon in hairy cell leukemia. AB - Alpha-interferon (IFN) and 2'-deoxycoformycin (dCF) both exhibit substantial activity in the treatment of hairy cell leukemia (HCL). Anecdotal reports have suggested that patients who failed IFN could achieve durable responses with dCF, although the frequency with which this was said to have occurred was unknown. We reviewed the available data on the responsiveness of HCL to dCF after IFN therapy by analyzing cases reported in the literature and those treated under the Special Exception mechanism of the National Cancer Institute, Division of Cancer Treatment. Of 60 such cases identified there were 22 (37%) "compete responses" and 22 (37%) "partial responses" for a total response rate of 74%. Responses appeared to be durable in many cases, lasting up to 2 years at the time of reporting. dCF is an active agent in HCL both as initial therapy and for the salvage of patients who have failed IFN. The relative activity of these two agents and the optimal strategies for their use are currently under investigation in ongoing clinical trials. PMID- 2583257 TI - Idarubicin in combination with intermediate-dose cytarabine in the treatment of refractory or relapsed acute leukemias. AB - 13 patients with refractory or relapsed acute lymphoblastic leukemia (ALL) and 7 patients with acute myeloid leukemia (AML) were treated with a regimen that included idarubicin 12 mg/m2 intravenously daily for 3 d plus cytarabine 2 g/m2 by infusion over 3 hours daily for 3 d. There were 10 remissions (ALL:7; AML:3) in the 15 relapsed patients and 4 (ALL:3) in the 5 patients with primary refractory disease. Severe myelosuppression was observed in all patients. Toxicity of this regimen caused nausea and vomiting, stomatitis, infections and/or liver enzymes increase. Cardiac toxicity was not observed. 2 patients died in aplasia of Gram-negative septicemia and brain hemorrhage. In conclusion, the combination of idarubicin and intermediate-dose cytarabine (IDARA-C) seems to be highly effective and sufficiently well-tolerated for the treatment of refractory and relapsed acute leukemias. PMID- 2583258 TI - Treatment of multiple myeloma in old patients. Finnish Leukaemia Group. AB - Patients aged 70 yr or older with multiple myeloma were treated, when suitable, according to concurrent trial protocols for younger patients, with the exception that the cytostatic regimen was not allocated at random. Intermittent melphalan and prednisone (MP) was given as the primary treatment to 42 patients and 5-drug combination MOCCA to 68 patients. The groups were comparable with each other, and the distribution of the clinical stages of the patients was similar to the younger patients in concurrent trials. An at least 50% response was achieved in 33% (SE 7.3) with MP and in 75% (SE 5.3) with MOCCA. The median survival times were 39 and 32 months, the relative age-adjusted survival times 45 and 41 months, respectively. Advanced age as such is thus no contraindication for active treatment of myeloma, and in suitable patients the results compare well with those achieved in younger patients. PMID- 2583259 TI - Primarily asymptomatic low-grade non-Hodgkin lymphomas: prediction of symptom free survival and total survival. AB - Low-grade non-Hodgkin lymphomas (NHL) constitute a group of tumours with an often long survival time but, at present, with little--or no--chance of cure if the disease is not strictly local. In primarily asymptomatic patients, treatment may either be started immediately after diagnosis or deferred until symptoms occur. The possibility of predicting the symptom-free time was investigated in 64 non selected initially asymptomatic patients with advanced low grade NHL, all of whom had treatment deferred until symptoms occurred. The most powerful predictor was the histopathological subgroup. Lymphocytic (LC) and follicular centroblastic centrocytic (fCBCC) lymphomas had a median symptom-free period of 2 years, which was four times longer than that for immunocytoma (IC) and follicular and diffuse CBCC (fdCBCC). In addition, the serum levels of deoxythymidine kinase (S-TK) and lactic dehydrogenase (S-LDH) could predict the symptom-free period. This did not apply to S-Haptoglobin, S-Orosomucoid or stage. In a multivariate analysis, only S-TK gave additional information to histopathology. The only variable that predicted the overall survival time was the length of the symptom-free period. PMID- 2583260 TI - Skin involvement in B-cell prolymphocytic leukaemia. PMID- 2583261 TI - Spontaneous remission of essential thrombocythaemia during two consecutive pregnancies. PMID- 2583262 TI - Rapid response to recombinant interferon alpha 2B and high-dose prednisone in multiple drug-resistant multiple myeloma. PMID- 2583263 TI - Ascites in a case of IgD-myeloma with myelofibrosis demonstration of the cIg in ascitic plasma cells. PMID- 2583264 TI - Platelet aggregation in polycythemia vera. PMID- 2583265 TI - Identification of the N-tosyl-L-phenylalanyl chloromethylketone modification site in Thermus thermophilus elongation factor Tu. AB - EF-Tu from Thermus thermophilus was first labelled with N-[14C]tosyl-L phenylalaninechloromethylketone and then cleaved by the combined action of CNBr and trypsin. The resulting peptides were separated by reversed-phase HPLC. Analysis of the isolated, labelled peptide led to the identification of a sequence which was identical to residues 76-88 in T. thermophilus EF-Tu. The TPCK reactive site is at Cys-82. Kinetic measurements of the incorporation of TPCK into native EF-Tu and EF-Tu nicked at position Arg-59 were performed. The results provide evidence that the cleavage of the peptide bond between Arg-59 and Gly-60 does not lead to a dramatic conformational change of EF-Tu at the aa-tRNA binding site. PMID- 2583267 TI - The histones of Caenorhabditis elegans: no evidence of stage-specific isoforms. An overview. AB - The nematode Caenorhabditis elegans expresses one species of H2A and one species of H4 molecules, at least two species of H1 (H1.1, H1.2), two species of H2B (H2B.1, H2B.2) and 2-4 species of H3 (H3.1 and H3.3 and an unassigned Ile/Leu microheterogeneity in H3). The study of their primary structures has been completed now and all of them, with the exception of the Ile/Leu microheterogeneity in H3, have been assigned to protein spots on two-dimensional gels. One spot, previously designated H3.2, probably represents C-terminally cleaved H3.1. The relative abundance of the isohistones was essentially the same when derived from either eggs, gravid adults or postreproductive, senescent worms. The degree of post-translational modification, however, particularly acetylation of H2A, H2B and H3 histone species, was reduced at old age. PMID- 2583266 TI - Raison d'etre and structural model for the B-Z transition of poly d(G-C).poly d(G C). AB - In DNA oligonucleotides crystallized in the A form, the nucleotides adopt standard conformation except for steps 5'-CpG-3' where reduced base-pair twist and a sliding motion of the base pairs along their long axes causes pronounced interstrand guanine-guanine overlap. As a consequence, torsion angles alpha, beta and gamma are consistently trans, trans, trans instead of the common-gauche, trans, +gauche. This conformation significantly increases the intraresidue distance between the guanine base and the 5'-phosphate group. A molecular model of poly d(G-C).poly d(G-C) built with these structural characteristics in the A form, which we call A2-DNA, shows that rotation of the guanosine sugar into the syn orientation is easily achieved and pushes the base pair across the helix axis. If successive guanosines are changed this way, a smooth transformation occurs to the left-handed Z-DNA. We suggest that A- and A2-DNA forms of poly d(G C).poly d(G-C) are metastable and that the actual transition is B in equilibrium (A in equilibrium A2) in equilibrium Z-DNA. PMID- 2583269 TI - Secretory protein synthesis in Chironomus salivary gland cells is not coupled with protein translocation across endoplasmic reticulum membranes. Electron microscopic evidence. AB - Fragments of rough endoplasmic reticulum containing polysomes bound to the membranes only at the 5 end were visualized in electron microscopic spreads from Chironomus thummi salivary gland cells. The length of the nascent protein molecules in the polysomes increased from the 5 to the 3 (free) polysome end. The data obtained disagree with the generally accepted model according to which synthesis of secretory proteins is concomitant with the protein transport across the endoplasmic membrane. PMID- 2583268 TI - Glycosylated forms of nuclear lamins. AB - Chromatin and pore complex-lamina preparations were obtained from pig and chicken tissues, and their proteins were analysed by mono- and bidimensional electrophoresis. A glycosylated form of lamin A, recognized by concanavalin A, was shown to be present in at least 3 of the tissues examined. Glycosylation is suggested to be a further postsynthetic modification, besides phosphorylation and methylation, which can modify the properties of lamins. PMID- 2583270 TI - Alkaloid homoharringtonine inhibits polypeptide chain elongation on human ribosomes on the step of peptide bond formation. AB - The aim of the present study was to investigate homoharringtonine alkaloid effect on: (i) the nonenzymatic and eEF-1-dependent Phe-tRNAPhe binding to poly(U) programmed human placenta 80 S ribosomes; (ii) diphenylalanine synthesis accompanying nonenzymatic Phe-tRNAPhe binding; and (iii) acetylphenylalanyl puromycin formation. Neither nonenzymatic nor eEF-1-dependent Phe-tRNAPhe binding were noticeably affected by the alkaloid, whereas diphenylalanine synthesis and puromycin reaction were strongly inhibited by homoharringtonine. It has been proposed that the site of homoharringtonine binding on 80 S ribosomes should overlap or coincide with the acceptor site of the ribosome. PMID- 2583271 TI - Translational active mRNPs from rabbit reticulocytes are qualitatively different from free mRNA in their translatability in cell-free system. AB - The translatability of polyribosomal and free mRNPs from rabbit reticulocytes and their mRNA was compared. Both classes of mRNPs turned out to be active in rabbit reticulocyte lysates. Considerable differences between mRNPs and mRNA have been revealed. The most striking feature of mRNPs was that high concentrations of mRNPs do not inhibit protein biosynthesis, whereas high concentrations of mRNA strongly inhibit this process. This inhibition is specific for mRNA and does not occur at the addition of the same amount of rRNA from E. coli. The features of mRNP translation are not the result of addition of the supplementary translation factors within particles. The specific function of mRNP proteins in the process of translation is under discussion. PMID- 2583272 TI - Characterization of two different peptides from the venom of the scorpion Buthus sindicus. AB - Two disulfide-rich, low-molecular mass peptides (approximately 3 kDa and approximately 4 kDa) have been isolated from Buthus sindicus venom using ion exchange and reverse-phase HPLC. Peptide I has 35 residues with 8 half-cystine residues and is clearly related to four-disulfide core proteins of the neurophysin type and to toxins of other scorpion species (55-63% residue identity). Peptide II, present in low yield, has 28 residues with 6 half-cystine residues and a structure largely dissimilar from that of peptide I and other characterized toxins, although probably still a member of the disulfide core peptide type. Consequently, scorpion venom contains, in addition to toxins characterized before, toxin-like compounds with distant relationships. PMID- 2583273 TI - Photocrosslinking demonstrates proximity of a 34 kDa membrane protein to different portions of preprolactin during translocation through the endoplasmic reticulum. AB - Photocrosslinking has been used to identify integral proteins of the endoplasmic reticulum membrane that are in proximity to nascent preprolactin during in vitro translocation. A photoreactive lysyl derivative was introduced into truncated preprolactin chains comprising 86 or 115 amino acids. Both with the 86mer, containing the reactive group in the signal sequence, and with the 115mer, containing the probe exclusively in the mature portion of the chain, photocrosslinking occurred to an approximately 35 kDa transmembrane glycoprotein, the signal sequence receptor (SSR). SSR is identical with a previously isolated abundant and ubiquitous 34 kDa membrane protein that appears to be essential for protein translocation. PMID- 2583274 TI - A luminescence probe for metallothionein in liver tissue: emission intensity measured directly from copper metallothionein induced in rat liver. AB - We report the first use of an emission probe based on the Cu(I)-thiolate chromophore, for the direct observation of copper metallothionein located in samples of rat liver. Elevated synthesis of Cu-MT in the rat liver was induced by subcutaneous injections of a series of aqueous CuCl2 solutions containing increasing amounts of Cu(II). Luminescence intensity in the 600 nm region, detected from frozen solutions of Cu-MT and from slices of the liver frozen at 77 K, following excitation in the 300 nm region, was dependent on the concentration of the Cu(II) used in the inducing solution. No such luminescence intensity was found for control samples obtained from the livers of rats not exposed to copper salts. It is suggested that this new method will allow direct visualization of Cu MT in tissue where genetic disorders impare copper metabolism. PMID- 2583275 TI - Affinity chromatography of the bovine cerebral cortex A1 adenosine receptor. AB - An approximate 140-fold purification of the A1 adenosine receptor of bovine cerebral cortex has been obtained via affinity chromatography. The affinity column consists of Affi-Gel 10 coupled through an amide linkage to XAC, a high affinity A1 adenosine receptor antagonist. As assessed by [3H]XAC binding, bovine brain membranes solubilized with the detergent CHAPS had a specific binding activity of 1.1 pmol/mg protein. Interaction of solubilized A1 adenosine receptors with the XAC-Affi-Gel was biospecific and 30% of the receptor activity was bound by the gel. Demonstration of [3H]XAC binding in the material eluted from the column with R-PIA required insertion of receptor into phospholipid vesicles. The specific activity of the affinity column purified receptor was 146 +/- 22 pmol/mg protein with typically 5-15% of the bound receptor recovered. The purified receptor displayed high-affinity antagonist binding and bound agonists with the potency order expected of the bovine brain A1 adenosine receptor: R-PIA greater than S-PIA greater than NECA. In purified preparations, the photoaffinity probe [125I]PAPAXAC-SANPAH specifically labelled a protein of molecular mass 38,000 which has previously been shown to be the A1 adenosine receptor binding subunit. PMID- 2583276 TI - Heat-stable translational inhibitor from rabbit reticulocyte lysates. AB - We have purified to apparent homogeneity a heat-stable (HS) factor from the postribosomal supernatant of rabbit reticulocyte lysates [(1988) FEBS Lett. 236, 479-483]. HS inhibits translation in hemin-supplemented lysates and induces phosphorylation of the alpha-subunit of the eukaryotic initiation factor 2 as does hemin deficiency. The translational inhibition produced by addition of HS to hemin-containing reticulocyte lysates and the accompanying phosphorylation of the eIF-2 alpha subunit can be prevented or reversed by NADPH generators including glucose 6-phosphate, NADPH itself, and also by dithiols, e.g., dithiothreitol, but not by fructose 1,6-bisphosphate or by monothiols, e.g., 2-mercaptoethanol. When added to crude preparations of the proinhibitor form (proHCI) of the heme controlled translational inhibitor (HCI), HS produces a pronounced increase of the HCI to proHCI ratio. It appeared possible that HS might be oxidized glutathione (GSSG) but this is not the case, for HS is not a substrate for highly purified glutathione reductase from rabbit erythrocytes. The spectral analysis of highly purified HS is consistent with the idea that HS could be a nucleotide derivative. PMID- 2583277 TI - Amino acid sequence of cinnamomin, a new member of the elicitin family, and its comparison to cryptogein and capsicein. AB - The phytopathogenic fungi Phytophthora cinnamomi cause systemic leaf necrosis on its non-host tobacco; in culture, it secretes a protein, called cinnamomin, which elicits leaf necrosis and protects tobacco against the pathogen Phytophthora nicotianoe, in a way similar to cryptogein and different from capsicein, elicitins of known amino acid sequences. The cinnamomin sequence has been determined and compared to other elicitins. The differences in the 3 elicitin sequences were correlated to the biological activities: 2 lysines were ascribed as the key amino acids involved in the differential control of protection with respect to necrosis. PMID- 2583278 TI - A chemically transformed rat fibroblast cell line expresses high levels of oncomodulin. AB - Chemically (by N-methyl-N'-nitro-N-nitrosoguanidine) treated rat fibroblasts (T14c) exhibited growth characteristics and a morphology typical for transformed cells and markedly different from untreated, parental cells. In contrast to untransformed cells, T14c fibroblasts produced significant levels of oncomodulin mRNA as analyzed on Northern blots even when compared to rat Morris hepatomas, the richest source of oncomodulin known so far. The levels of transcripts for both calmodulin and oncomodulin in T14c cells were higher in log phase growth as compared to confluent stages. The T14c model system may be useful in the elucidation of mechanisms involved in the regulation of oncomodulin synthesis. PMID- 2583279 TI - Conserved residues of tumour necrosis factor and lymphotoxin constitute the framework of the trimeric structure. AB - Four distinct areas of primary sequence conservation between known tumour necrosis factor and lymphotoxin polypeptides from various species can be recognized. When these amino acid sequences are highlighted in the three dimensional structure, all are found in the same region, constituting the framework of the trimeric structure. PMID- 2583280 TI - Amino acid sequences of cytotoxin-like basic proteins derived from cobra venoms. AB - Amino acid sequences of cytotoxin-like basic proteins (CLBPs), purified from the venoms of Formosan cobra (Naja naja atra) and Indian cobra (Naja naja), were reinvestigated. The determined sequences differed from those reported previously by Takechi et al. [(1985) Biochem. Int. 11, 795-802; (1987) Biochem. Int. 14, 145 152]. The sequence of CLBPs at residues 25-30 was found to be hydrophilic as compared with those of cytotoxins. The difference in the hydrophobicity of this region might be responsible for the difference in their cytotoxic activities. PMID- 2583281 TI - Effect of denervation on the androgen-induced expression of actin and CPK mRNAs in the levator ani muscle of the rat. AB - In the adult male rat, the castration-induced atrophy of the levator ani (LA) muscle was found to be associated with a decrease in the relative levels of both actin and creatine phosphokinase (CPK) mRNAs. The typical recovery of these two sequences following 5 days of testosterone propionate (TP) replacement therapy was not impaired by the bilateral denervation of the LA. This indicated that TP was the sole trophic factor regulating the plasticity of these two mRNAs and challenged the hypothesis that androgen action might be neuronally mediated. The observation that denervation led to a severe repression of both actin and CPK messages only in the absence of TP replacement therapy suggested that the nerve impulse could play an accessory role in the control of their expression. PMID- 2583282 TI - Tight binding dopamine reuptake inhibitors as cocaine antagonists. A strategy for drug development. AB - The experiments reported in this study tested the hypothesis that tight binding dopamine (DA) reuptake inhibitors might act as cocaine antagonists. Binding studies demonstrated that the high affinity dopamine reuptake inhibitor, 1-[2 [bis(4-fluorophenyl)methoxy]ethyl]-4-[3-phenylpropyl]piperazine (GBR12909) produced a wash-resistant inhibition of the DA transporter in rat striatal membranes as labeled by [3H]cocaine or [3H]1-[2-(diphenyl- methoxy)ethyl]-4-(3 phenylpropyl)piperazine [( 3H]GBR12935), indicative of tight binding. In vivo microdialysis experiments showed that administration of 25 mg/kg GBR12909 to rats produced a modest, but not statistically significant, increase in the extracellular levels of striatal DA, while this same dose of GBR12909 inhibited the ability of cocaine to elevate extracellular DA levels by 64%. These data suggest that tight binding DA reuptake blockers may provide a fruitful approach for developing a cocaine antagonist. PMID- 2583283 TI - Testing topological models for the membrane penetration of the fusion peptide of influenza virus hemagglutinin. AB - Low pH-induced binding of the bromelain-solubilized form of influenza virus hemagglutinin (BHA) to membranes occurs through the fusion peptide. From asymmetric hydrophobic photolabeling of membranes, evidence was obtained that this peptide penetrates only one leaflet of the bilayer. The asymmetrical labeling was achieved by employing a photoreactive analogue of a fatty acid whose transbilayer distribution can be manipulated by a membrane proton gradient. PMID- 2583284 TI - Differential allosteric effects of 8-(N,N-diethylamino)octyl-3,4,5 trimethoxybenzoate-HCl (TMB-8) on muscarinic receptor subtypes. AB - TMB-8, a putative inhibitor of intracellular calcium mobilization, prevents the binding of the muscarinic ligand N-[3H]methylscopolamine. The inhibition was observed in four tissues from guinea pig; cortex, heart, pancreas, and ileum, representing M1, cardiac M2, glandular M2, and heterogeneous M2 subtypes of muscarinic receptors, respectively. The Ki values for all four tissues were approx. 4 microM. However, dissociation kinetics revealed that TMB-8 interacted with an allosteric site of three muscarinic receptor subtypes but not the subtype from pancreas. These results indicate that TMB-8 interacts with muscarinic receptors, and therefore would disrupt calcium mobilization or any second messenger system coupled to these receptors. PMID- 2583285 TI - Antisera against an acetylcholine receptor alpha 3 fusion protein bind to ganglionic but not to brain nicotinic acetylcholine receptors. AB - Neuronal nicotinic acetylcholine receptor (AChR) subtypes have been defined pharmacologically, immunologically, and by DNA cloning, but the correlations between these approaches are incomplete. Vertebrate neuronal AChRs that have been isolated are composed of structural subunits and ACh-binding subunits. A single kind of subunit can be used in more than one AChR subtype. Monoclonal antibody (mAb) 35 binds to structural subunits of subtypes of AChRs from both chicken brain and ganglia. By using antisera to a unique sequence of alpha 3 ACh-binding subunits expressed in bacteria, we show that ganglionic AChRs contain alpha 3 ACh binding subunits, whereas the brain AChR subtype that binds mAb 35 does not. Subunit-specific antisera raised against recombinant proteins should be a valuable approach for identifying the subunit composition of receptors in multigene, multisubunit families. PMID- 2583286 TI - A cytocidal tissue kallikrein isolated from mouse submandibular glands. AB - A cytocidal factor against mouse thymocytes was purified from the submandibular glands of female BALB/c mice using Sephadex G-50 gel filtration chromatography and reverse-phase HPLC. SDS-PAGE and amino acid sequence analysis revealed that the cytocidal factor was mouse glandular kallikrein (mGK)-6. mGK-6 showed an optimal enzyme activity at pH 10 and a cytocidal activity against thymocytes in a dose-dependent manner. PMID- 2583287 TI - Maturation of nuclear lamin A involves a specific carboxy-terminal trimming, which removes the polyisoprenylation site from the precursor; implications for the structure of the nuclear lamina. AB - Lamin A, a nuclear lamina protein of differentiated cells, is synthesized as a precursor of the mature molecule. Protein sequencing of the carboxy-terminal 14 kDa fragment shows a lack of the last 18 residues predicted by cDNA sequencing. The carboxy-terminal proteolytic maturation explains previous biochemical results including the loss of the polyisoprenylation site now located to the CXXM motif at the end of the chain. This view and earlier results on lamin B predict multiple post-translational modifications shared by lamins A and B. While retained by lamin B, which is present in all cells, they are lost by maturation from lamin A, which probably acts only as an additional lamina constituent in differentiated cells. PMID- 2583289 TI - A cross-linked complex between horse pancreatic lipase and colipase. AB - The water soluble carbodiimide N-cyclohexyl-N'-2-morpholinoethyl-carbodiimide methyl-p-toluolsulfona te was found to effectively covalently cross-link pancreatic colipase to lipase as evidenced by Western blotting experiments using antibodies directed either against lipase or colipase. Moreover the resulting covalent complex has a Mr consistent with a stoichiometry of 1 mol colipase per mol lipase. Cross-linked lipase and colipase retain their activity implying a correct covalent binding between the two proteins. The specificity of the lipase colipase binding was further supported by the very low amount of cross-linked products when lipase or colipase alone were incubated in the presence of carbodiimide. The formation of a covalent lipase-colipase complex in the presence of carbodiimide clearly demonstrates that the binding between both proteins involves ion pairing. Furthermore, the formation of an active covalent complex strongly suggests that the lipase-colipase binding site is distinct from the colipase interfacial recognition site as well as from the lipase catalytic site. PMID- 2583288 TI - Wheat germ agglutinin but not concanavalin A modulates protein kinase C-mediated phosphorylation of red cell skeletal proteins. AB - Human red blood cells contain protein kinase C (PKC) which acts exclusively on the membrane skeletal proteins band 4.1, band 4.9 and adducin. PKC activity can be stimulated by the addition of the phorbol ester 12-O-tetradecanoyl phorbol 13 acetate to intact cells. Phosphorylation of band 4.1 by PKC in vitro results in a dramatic reduction in band 4.1 binding to spectrin and actin, as well as to the cytoplasmic domain of band 3. Here we show that the lectin wheat germ agglutinin (WGA), which binds to the extracellular domain of glycophorin results in the inhibition of PKC catalyzed phosphorylation of band 4.1, band 4.9 and likely adducin as well. The lectin concanavalin A, which binds to band 3 was without effect. Our results suggest that the binding of WGA to glycophorin results in a major rearrangement of the membrane skeletal network which correlates with reduced phosphorylation of membrane skeletal proteins by PKC. PMID- 2583290 TI - Adrenal chromaffin granules and secretory granules from thyroid parafollicular cells have several common antigens. AB - The presence of various antigens in two types of isolated endocrine vesicles (chromaffin granules and secretory vesicles of thyroid parafollicular cells) was investigated by immunoblotting. The two types of vesicles have three common secretory proteins: chromogranin A, chromogranin B and secretogranin II. Furthermore, six common membrane antigens were found: cytochrome b-561, carboxypeptidase H, glycoprotein II, glycoprotein III, synaptin/synaptophysin and SV 2. These results demonstrate that vesicles obtained from neural crest-derived endocrine cells not only share several common secretory peptides and proteins, but also have common properties as far as their membrane antigens are concerned. PMID- 2583291 TI - Imaging of cell membraneous and cytoskeletal structures with a scanning tunneling microscope. AB - The first observation of unstained cell membraneous structures by a scanning tunneling microscope is reported. An adhesive preparation method was used for imaging human medulloblastoma cells from the cell line TE 671 and oocytes from the clawed toad Xenopus laevis. The images show filaments, stacks of molecules and hilly structures. The possible identify of the filamentous structures is discussed, although the observed structures cannot yet be fully characterized. The work suggests possible future experiments on various biological structures in their natural environment. PMID- 2583293 TI - [The provisional health and hygiene requirements for cooperatives and individual labor in the production and sale of food products]. PMID- 2583292 TI - Alcohol-related problems in high-risk groups. Report on a WHO study. PMID- 2583294 TI - [Brucellosis]. PMID- 2583295 TI - [Salmonelloses]. PMID- 2583297 TI - [The pathogenesis of nervous and mental disorders in children]. PMID- 2583296 TI - [The premature child: the causes of prematurity and the characteristics of such infants]. PMID- 2583298 TI - [Angiitis (vasculitis) of the skin]. PMID- 2583300 TI - [Ligament injuries of the ankle joint]. PMID- 2583299 TI - [Pyogenic granuloma (botryomycosis)]. PMID- 2583301 TI - [Lumbosacral radiculitis in coal miners]. PMID- 2583302 TI - [Current approaches to conducting anti-alcohol health education work by paramedical personnel]. PMID- 2583303 TI - [Current trends in the prevention of drug addiction and abuse abroad]. PMID- 2583304 TI - [Herbal treatment in nervous system diseases]. PMID- 2583305 TI - [Complicated infected abortion]. PMID- 2583306 TI - [Sepsis in a female patient with pneumonia]. PMID- 2583307 TI - [Ovarian cystoma]. PMID- 2583308 TI - [Conservative therapy of uterine myoma]. PMID- 2583309 TI - [The sanatorium-health resort treatment of children together with the parents]. PMID- 2583310 TI - [Changes in anti-thyroid hormone and anti-thyroglobulin antibodies during thyroid hormone(s) or prednisolone treatments in 3 cases of Hashimoto's thyroiditis]. AB - We have experienced 3 cases of Hashimoto's thyroiditis with anti-thyroid hormone antibodies. Changes in titers of anti-thyroglobulin(Tg) and anti-thyroid hormone antibodies during 6 year (Cases 1 and 2) and 7 year (Case 3) observation periods were examined in each case. Cases 1 (13-year-old) and 2 (10-year-old) are sisters with hypothyroidism whose chief complaint was short stature. They were diagnosed as having Hashimoto's thyroiditis by needle biopsy of the thyroid gland. Presence of anti-thyroid hormone antibodies were found in the sera of both cases (Case 1: anti-thyroxine(T4) antibodies, Case 2: anti-triiodothyronine(T3) antibodies). They were treated with synthetic T4 or combined therapy of T3 and T4, and serial sera obtained during the 6 year treatment period were tested for the titers of anti-Tg and anti-thyroid hormone antibodies. Case 3 (23-year-old female), who was diagnosed as having Hashimoto's thyroiditis associated with systemic lupus erythematosus (SLE) and Sjogren's syndrome had been treated with prednisolone(PSL) for 8 years. After one year of strating the treatment, she was found to have unusually low serum T3 measured by radioimmunoassay. Further examination revealed the presence of anti-T3 antibodies in her serum. Serial sera obtained during the 7 year observation period were tested for the titers of anti Tg and anti-T3 antibodies. In cases 1 and 2, replacement therapy with thyroid hormone resulted in the decrease of titers of anti-thyroid hormone antibodies. In addition, increase in serum TSH concentrations was accompanied with increased titers of anti-Tg and anti-thyroid hormone antibodies in all 3 cases. The exact mechanism for it is not clear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583311 TI - [Fluctuations in the titers of anti-thyroid hormone and anti-thyroglobulin antibodies in 4 cases of Graves' disease during long-term treatment period]. AB - We studied 4 cases of Graves' disease with anti-thyroid hormone antibodies. Changes in the serum levels of triiodothyronine(T3), thyroxine(T4), free T4, thyrotropin(TSH), and thyroglobulin(Tg), as well as titers of anti-Tg antibodies, anti-thyroid hormone antibodies, anti-TSH receptor antibodies(TRAb) and anti microsomal antibodies(MCHA) during 2 10 years' treatment periods were examined in each case. Case 1; A woman, who was diagnosed as having Graves' disease when she was 10 years old, had been treated with methimazole(MMI) or propylthiouracil(PTU). Treatment with the antithyroid drug had been discontinued by herself when she was 19 years old until she was 24 years old, when she was pregnant and consulted our hospital. Since her serum levels of T3 were unusually high, examination of her serum for the presence of anti-T3 antibodies was done. The presence of anti-T3 antibodies in her serum was confirmed. Case 2; A woman, who was diagnosed as having Graves' disease at the age of 41, had been treated with MMI or PTU. Presence of serum anti-T3 antibodies was found in a screening test for the antibodies. Serial sera were obtained during the 5 year observation period when she was treated with MMI, PTU, and subtotal thyroidectomy. Titers of anti-Tg antibodies in her sera were in the normal range. Case 3; A woman, who was diagnosed as having Graves' disease at the age of 11, had been treated with MMI or PTU. Presence of anti-T3 and anti-T4 antibodies were found in her sera in a screening test. Serial sera obtained during the 4 year treatment period were tested. Case 4; A woman, who was diagnosed as having Graves' disease at the age of 14, had been treated with MMI. Presence of anti-T3 and anti-T4 antibodies was found in her sera in a screening test. Serial sera obtained during the 2 year treatment period were tested. Titers of anti-Tg were increased when the levels of TSH or titers of TRAb were increased. The results suggested that TSH and TRAb, which are thyroid stimulating substances, increased serum levels of Tg, which resulted in the increase of titers of anti-Tg. Because of the possibility that administration of PSL could modify B lymphocyte functions, periods during which PSL was administered were excluded from the examination of the correlation between Tg concentrations or titers of anti-Tg and titers of anti-thyroid hormone antibodies, as in Cases 2 and 4, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2583312 TI - [Non-aromatizing androgen 19-hydroxylase in human fetal organs]. AB - 19-hydroxyandrostenedione (19-OH A), known for many years as an obligatory intermediate of estrogen biosynthesis, has recently been found to be an amplifier of aldosterone action and in itself a hypertensinogenic steroid (J. Steroid Biochem., 16; 329, 1982). To search the presence of a non-aromatizing andorgen 19 hydroxylase in fetal organs, metabolism of labeled androstenedione(A) in fetal adrenal, liver, lung, brain and kidney was studied. 19-hydroxylase activity was calculated by the amounts of 19-OH A formed from A. The tissue homogenate was incubated with [4-14C]A and NADPH for different periods of time under air. The product, [4-14C] 19-OH A with added carrier standard [6,7-3H] 19-OH A was separated and purified by TLC, acetylation and TLC to constant 3H/14C ratio. The identity of the product was established by C.C.D. and by GC-MS analysis of purified product 19-AcOA in a larger scale adrenal incubation of non-labeled A. 19-hydroxylase activity was 0.9 pmol/min/mg protein for adrenal, but there was a negligible quantity of 19-OH A in lung, brain and kidney. Estrogen production was also assayed by 3H-water method using [1 beta-3H, 4-14C] A (3H/14C = 69.9). No detectable amount of estrogen was found in incubation of any homogenate except for liver. These results indicate that the non-aromatizing 19-hydroxylase activity in fetal adrenal gland is much higher than that in other organs. This is the first report to demonstrate the presence of 19-hydroxylase in human fetal adrenal tissue. It is suggested that 19-OH A secreted from fetal adrenal may also be associated with serum concentration of fetal circulation. PMID- 2583313 TI - [Cellular immune dysfunction in the NOD mouse: suppression of concanavalin A induced responses in spleen cells by activated macrophages]. AB - It is generally accepted that T lymphocyte-mediated autoimmunity contributes to the pathogenesis of Type 1 diabetes in humans and animals. Using spleen cells from nonobese diabetic (NOD) mice, a model of human Type 1 diabetes, we have analyzed the subset of T lymphocytes by flow cytometry and investigated concanavalin A (Con A)-induced interleukin 2 (IL-2) production and cell proliferation. NOD mice showed a higher percentage of Thy1.2+, L3T4+, and Lyt2+ T lymphocytes than did control ICR mice through the whole age examined. Spleen cells from a large majority of NOD mice were found to generate very low IL-2 production and cell proliferation in response to Con A. However, a few mice preserved their responsiveness to Con A. The following reasons may indicate that macrophage-mediated suppression participates in the deficient function of NOD spleen cells. (a) Macrophage depletion from NOD spleen cells retrieved Con A induced IL-2 production. (b) Thioglycollate-induced peritoneal exudate cells containing many activated macrophages could completely suppress cell proliferation. (c) Prostaglandin synthetase inhibitor indomethacin reversed the suppression of IL-2 production by macrophages. (d) Conversely, exogenous prostaglandins could show the partial suppression of IL-2 production. These results suggest that activated macrophages suppress the response of NOD spleen cells to Con A mostly through prostaglandins. This impairment may contribute to the pathogenesis of Type 1 diabetes in NOD mice. PMID- 2583314 TI - [Assay of activated form of progesterone receptor with ATP-sepharose column chromatography]. AB - Biological actions of progesterone are correlated with the ability of the progesterone receptor(PR) to bind to nuclear acceptor sites. Measurement of not only the presence of PR in a tissue but also the amount of that receptor which is able to bind to nuclear acceptor sites is important in predicting tissue response to progesterone. Activation of PR is required for effective binding to chromatin. Since the dextrancoated charcoal assay does not distinguish between an activated and a non-activated receptor, a rapid, relatively simple assay is needed which can account for an activated form of PR. Therefore, ATP-Sepharose column chromatography was tested to identify an activated form of PR. PR in crude uterine cytosol from estrogen-primed immature rabbits was labeled with 3H progesterone at 0 degree C. The labeled PR was then incubated at 4 degrees C with uterine chromatin from ovariectomized mature rabbits. The freshly prepared PR had little capacity to bind to the chromatin. After activation manipulation at low temperature, low ionic strength and neutral pH, this PR was able to bind to chromatin approximately fourfold more than that activated by heating at 25 degrees C. The affinity of the activated and the non-activated PR for ATP was evaluated on ATP-Sepharose column chromatography. The activated PR was selectively adsorbed onto columns of ATP-Sepharose, and the binding ability of the activated PR to ATP paralleled that of the rabbit uterine chromatin. These results suggest that ATP-Sepharose column chromatography could be useful to identify an activated PR as a substitute for chromatin binding assay. PMID- 2583315 TI - Can we make time for children? The economy, work schedules, and child care. PMID- 2583316 TI - Mother or market? Effects of maternal employment on the intellectual ability of 4 year-old children. AB - This article uses the 1986 Children of the National Longitudinal Survey of Youth data set to investigate the impact of maternal employment on children's intellectual ability, as measured at the age of 4 by using the Peabody Picture Vocabulary Test (PPVT). Results from multivariate regression analysis show a statistically significant adverse effect of mother's employment on children's intellectual ability, but only for boys in higher income families. Furthermore, the negative impact was related to the timing of maternal employment: employment during the boys' infancy had a statistically significant negative effect on PPVT scores at the age of 4. This pattern was not found for girls, for children in low income families, or for families in which mothers resumed their employment after the child's first year of life. The impact of other demographic trends in recent years--declining fertility and rising marital instability--are also investigated. The results show an adverse effect of the presence of other siblings on children's PPVT scores; but holding family income constant, the effect of the parents' marital status on children's intellectual ability is not statistically significant. In addition, several family background factors are highly correlated with children's test scores. PMID- 2583317 TI - Mother-child relations and adolescent sexual attitudes and behavior. AB - We hypothesize that children who are close to their parents are more likely to have attitudes and behavior that are consistent with their parents' values than children who are not close to their parents. Using data from a probability sample of 888 mother-child pairs of white women in the Detroit metropolitan area, we tested this hypothesis, using both mother's and child's attitudes toward premarital sexual intercourse and the child's report of whether he or she had engaged in premarital sexual intercourse. Unlike most previous work in this area, which has posited a direct association between the closeness of the mother-child relation and the child's attitudes and behavior, we found that the quality of the relation interacted with the mother's attitudes in its effects on the child's attitudes and behavior. Children with close relations with their mothers were more likely to hold attitudes and behave in a manner consistent with their mothers' own attitudes than children with more distant relations. PMID- 2583318 TI - The antecedents of teenage fatherhood. AB - The High School and Beyond Survey was used to describe young men who are at risk of becoming teenage fathers and examine the causal process leading to early fathering for young men. Bivariate results show that men who are at risk of fathering children at a young age have unique attitudes and family, school, and dating experiences. Multivariate analyses suggest that the most cogent factors affecting teenage fathering include being black, going steady, and having unorthodox views about parenting outside of marriage. PMID- 2583319 TI - Pathways to independent living in early adulthood: marriage, semiautonomy, and premarital residential independence. AB - Data from the National Longitudinal Study of the High School Class of 1972 are used to examine factors influencing young adults' departure from the parental home and the initial pathways taken, including leaving home for marriage, residential semi-autonomy (Semi), and premarital residential independence (PRI). Parents' education and continuing in school decrease the likelihood of leaving home via marriage and increase the likelihood of leaving home via Semi or PRI. All other factors considered affect all pathways out of the parental home in the same direction, but in differing magnitudes. The predominant influences on PRI are indicators of modern family values, whereas the predominant influences on leaving home for marriage are measures of resources, both those of the parents and those of the young adults. PMID- 2583320 TI - National estimates of cohabitation. AB - Data from the 1987-1988 National Survey of Families and Households are used to provide national estimates of cohabitation trends and levels. The rapid increase since around 1970 is documented over both birth cohorts and marriage cohorts. Almost half of the persons in their early 30s and half of the recently married have cohabited. Changes in the proportion ever married are compared with changes in the proportion who have either married or cohabited. Much of the decline in marriage has been offset by increased living together without being married. The stability of unions of various types is compared. Cohabitations end very quickly in either marriage or disruption. About 60 percent of all first cohabitations result in marriage. Cohabiting unions and marriages preceded by cohabitation are much more likely to break up than are unions initiated by marriage. Multivariate analysis reveals higher rates of cohabitation among women, whites, persons who did not complete high school, and those from families who received welfare or who lived in a single-parent family while growing up. PMID- 2583321 TI - Living arrangements of the elderly in Fiji, Korea, Malaysia, and the Philippines. AB - Using logit techniques and data from surveys of the elderly conducted in 1984 under the auspices of the World Health Organization, this article investigates socioeconomic, cultural, and demographic determinants of living arrangements of the elderly. Having a spouse or children with whom to live has important effects on living arrangements. The results provide only weak support, however, for hypotheses based on modernization theory and point to the need for detailed data on transitions in living arrangements and for information about the younger generation as well as the older generation, both of which are involved in deciding who lives with whom. PMID- 2583322 TI - Forecasting mortality: a parameterized time series approach. AB - This article links parameterized model mortality schedules with time series methods to develop forecasts of U.S. mortality to the year 2000. The use of model mortality schedules permits a relatively concise representation of the history of mortality by age and sex from 1900 to 1985, and the use of modern time series methods to extend this history forward to the end of this century allows for a flexible modeling of trend and the accommodation of changes in long-run mortality patterns. This pilot study demonstrates that the proposed procedure produces medium-range forecasts of mortality that meet the standard tests of accuracy in forecast evaluation and that are sensible when evaluated against the comparable forecasts produced by the Social Security Administration. PMID- 2583323 TI - Black/white differences in health status and mortality among the elderly. AB - Grade of membership (GOM) representations are used to characterize and compare the health status of a very heterogeneous sample of blacks and whites in an elderly cohort of 2,806 noninstitutionalized men and women living in New Haven, Connecticut. They were interviewed in 1982 as part of the Established Populations for the Epidemiologic Study of the Elderly (EPESE). Ideal profiles based on functional disabilities, chronic diseases, and selected biomedical and behavioral risk factors are constructed empirically. Each individual in the sample is represented by a set of GOM scores, interpreted as degrees of similarity of his or her health record to each of the profiles. Four profiles emerge from GOM analyses: healthy elderly, elderly with cognitive impairment, elderly with impairment in mobility function and physical performance and with selected chronic conditions, and elderly with major limitations in activities of daily living and multiple chronic conditions. Although elderly blacks and whites generally have similar configurations of profiles, there are important differences, especially when chronic conditions are related to specific types of functional impairments. Questions about and claims for black/white mortality crossovers at older ages, usually addressed with aggregate data, are examined conditional on GOM scores that correspond to diverse combinations of disabilities (or lack thereof) together with housing characteristics of cohort members (e.g., whether they live in public housing for the elderly or in owned or rented housing in the community). PMID- 2583324 TI - A new look at the effect of venereal disease on black fertility: the Deep South in 1940. AB - The effect of venereal disease on black fertility is estimated for six Deep South states around 1940. Several relevant control variables are introduced, including characteristics of the socioeconomic environment and measures of possible diffusion processes that might have affected the relationship between venereal disease and fertility. The objective is to identify as precisely as possible the net effect of venereal disease on black fertility. The analyses are based on 395 counties in Alabama, Florida, Georgia, Louisiana, Mississippi, and South Carolina. The results indicate that venereal disease was significantly related to black fertility, but that the relationship was considerably weaker than some have suggested (most notably, Wright and Pirie, 1984). Furthermore, the revised estimates suggest that venereal infections probably accounted for around 28 percent of the historical decline in black fertility between 1875-1880 and 1935 1940. I conclude that the black fertility transition was not unicausal and that explanations for the black experience should be sought among the same causative forces considered for other populations. PMID- 2583325 TI - Demographic conditions responsible for population aging. AB - This article develops and applies two expressions for the rate of change of a population's mean age. In one, aging is shown to be negatively related to contemporary birth rates and death rates. In a general sense, aging occurs when vital rates are too low, as illustrated through applications to the United States, the Netherlands, and Japan. The other expression relates the rate of aging to a population's demographic history, in particular to changes in mortality, migration, and the annual number of births. Applications to the United States and Sweden show that the dominant factor in current aging in these countries is a history of declining mortality. Migration also contributes significantly but in opposite directions in the two countries. The two approaches are integrated after recognizing that the rate of change in the mean age is equal to the covariance between age and age-specific growth rates. A decomposition of this covariance shows that the two seemingly unrelated expressions contain exactly the same information about the age pattern of growth rates. PMID- 2583326 TI - Relating changes in life expectancy to changes in mortality. AB - I address the problem of what can be said of changes in mortality rates, if one knows how life expectancies change. I note a general formula relating life expectancies in different ages to mortality and prove that if mortality changes over time following a proportional-hazard model, then there is a one-to-one correspondence between life expectancy at birth and mortality rates. Extensions and an application of these results to the analysis of mortality change are presented. PMID- 2583327 TI - An alternative purging method: controlling the composition-dependent interaction in an analysis of rates. AB - The purging method controlling for the composition-group interaction developed by Clogg and his associates has proven useful in demographic research. This article proposes an alternative method, partial CD purging, that controls the interaction between composition and the dependent variable. The purged rates from this new method are invariant to changes in the marginal distribution of composition, but those from the earlier purging method are not. Mathematical relationships between the proposed method and other techniques are also explored. PMID- 2583328 TI - A flexible approach for the decomposition of rate differences. AB - Conventional methods of decomposing the difference between two rates, such as Kitagawa's classic component analysis, are confined to taking the average of compositional differences. I propose a more general modeling approach involving three steps: (1) A system of equations with the various additive components of the rate difference is set up; (2) unknowns (refined rate differences) are estimated with Clogg's purging method; (3) the components are calculated. I use an example of U.S. mortality data to compare the proposed method with the conventional ones. The method can be generalized to decompositions for multiple groups and for multiple confounding factors. Kitagawa's method is a special case of this general approach. PMID- 2583329 TI - [Initial results of studies of the effect of solar UV irradiation on the curative effect of psoriasis vulgaris in Heiligendamm]. AB - By simultaneous registration of individual dose of natural UV radiation and clinical determination of variation of skin lesions of patients with psoriasis vulgaris was derived a good correlation between both parameters. Furthermore, there were large differences in utilization of UV-light by patients. There are great reserves of a more effective therapy with solar radiation. PMID- 2583330 TI - [Phototherapy of parapsoriasis]. AB - The effectiveness of photo(chemo)therapy was tested on 69 patients with different forms of parapsoriasis (parapsoriasis guttata, n = 14; pityriasis lichenoides et varioliformis acuta, n = 6; and parapsoriasis en plaques, n = 49). The forms of parapsoriasis differed in their response to phototherapy and in their relapse rates. Whereas parapsoriasis guttata can be regarded as a definite indication for UVA therapy, much higher UVA doses are required for pityriasis lichenoides et varioliformis and the probability of relapses is higher. It was not possible to interrupt the relapsing course of parapsoriasis en plaqes in the majority of patients. Relapses occurred within 7 months in 63.2% of the cases. A healing effect that lasted for more than one year was achieved only in 18 patients. PMID- 2583331 TI - [The effect of the peptide dalargin on wound healing]. AB - The wound-healing agent Dalargin, a hexapeptide and varios of its cleavage products were tested in a wound-healing model on the basis of granulation in rat. Three days after wounding (p.op.) an increase in granulation was observed at Dalargin concentrations of 10 micrograms/ml and 50 micrograms/ml. Seven days p.op. an increase was observed already at a Dalargin concentration of 5 micrograms/ml. The cleavage products of Dalargin had no stimulating effect on granulation. A histologic differentiation of the different cell parts in the granulation tissue led to an increased total number of cells. The concentration of 5 micrograms/ml induced both an increase in the number of endothelial cells and fibroblasts, the concentration of 50 micrograms/ml induced just an increase of the number of endothelial cells. The possible bases of the mode of operation are being discussed. The stimulating effect on wound healing as described could be confirmed by the results obtained in our animal experiments. PMID- 2583332 TI - [The forensic value of morphologic-morphometric sperm differentiation in trace studies. I: Methods]. AB - Proceeded from examination of sperm samples of 200 men, controls of sperm samples from 81 men during a determined period (5 sperm samples from each man within a period up to 70 days) and in view of trace-conditioned influences, the feasibility of a morphologic-morphometric differentiation of spermatozoa is demonstrated with sperm traces and comparative material. The following items are shown: necessary marginal conditions such as quantity and quality of spermatozoa available, application of the elaborated 37-item spermiocytogram in connection with the introduced indices of identification as well as the observance of a maximum period of 30 days between the formation of a criminologically relevant sperm trace and the separation of comparative samples. The method is used in group identification in terms of criminological identification theory. PMID- 2583333 TI - [The nail file test--a method for the clinical differentiation of color changes in nails]. AB - A simple and rapid method for the identification of discolored nails is described. By peeling of the surface of the nail at the discolored site with a file distinction between tumor (in most cases malignant melanoma) or hematoma is possible. The extraction of the nail, which is more expensive and painful, becomes unnecessary. PMID- 2583334 TI - [Leiomyoma of the breast in the male]. AB - A macroscopically not sure classifiable solitary tumour on the nipple was observed in a 68 year old man. Histologically a pure leiomyoma was found. Therapy of choice is the tumour resection, if requested. PMID- 2583335 TI - Asymptomatic bacteriuria in normal and high-risk pregnancy. AB - A routine urine culture was performed in 1130 normal pregnant women and in 211 high-risk pregnancies (136 diabetics and 75 women with a previous urinary tract infection). Asymptomatic bacteriuria was found in 5.9% of the normal pregnancies, 12.5% among the diabetics and in 18.5% of the previous urinary tract infection patients. The higher incidence of a clinical urinary tract infection among patients with asymptomatic bacteriuria was found statistically significant (p less than 0.001) in all three groups. A high correlation was found between a negative urine culture in early pregnancy and the absence of development of cystitis and pyelonephritis in later pregnancy. The incidence of asymptomatic bacteriuria in normal pregnant women who developed cystitis later in pregnancy was 33.3% and in those developing pyelonephritis, 66%. In the two high-risk pregnancy groups, the incidence of asymptomatic bacteriuria among those developing clinical infection was even higher, 58.3 and 85.7%, respectively, among the diabetics, and 60 and 66.6% respectively, among the previous urinary tract infection patients. PMID- 2583336 TI - The effect of abortion on the incidence of pre-eclampsia. AB - The incidence of pre-eclampsia was studied in 9771 women that were pregnant for the first or second time. The protection offered by a previous pregnancy which ended in abortion was compared to that provided by a first pregnancy that proceeded to term. The rate of pre-eclampsia was 2.9% for primigravid women and was significantly lower (1.5%, p less than 0.001) for women giving birth for the second time. Adjusting by multiple regression for confounding factors (e.g., maternal age, social class, ethnic origin and smoking), the incidence of pre eclampsia was also significantly lower (p = 0.038) following an induced abortion, but not following a spontaneous abortion. PMID- 2583337 TI - Diabetes mellitus in pregnancy. Management and outcome of diabetic pregnancies in the state of Hesse, F.R.G.; a five-year-survey. AB - From 1982 to 1986, data of 446 pregnancies in diabetic women were compared to equivalent information on 111,390 unselected non-diabetic pregnancies with the help of the Hessische Perinatalstudie (Hessian Perinatal Study, HEPS), a computerized system of collecting information on obstetrical care in the state of Hesse, F.R.G. Patient histories, pregnancy risks, birth risks, fetal outcome and maternal well-being were evaluated to survey the current situation of diabetic pregnancies in the specific constellation of widely decentralized obstetrical management and to point out possible benefits of stronger centralization of these high-risk pregnancies. Perinatal mortality in children of diabetic mothers (4.89%) remains substantially higher than in children of non-diabetic mothers (0.63%), with two thirds of the fetal loss occurring before birth. Infant morbidity, including macrosomia, shows the same impact of maternal diabetes. Maternal post-partum morbidity is increased in diabetic women. 37.9% of children of diabetic mothers were delivered in obstetrical units equipped for maximal care, 17.5% in primary care level hospitals. Perinatal mortality and morbidity as well as maternal complications indicate that diabetic women should receive obstetrical care in those centers that can provide all the necessary facilities. PMID- 2583338 TI - Twinning in southern Israel; secular trends, ethnic variation and effects of maternal age and parity. AB - Twin births in southern Israel between 1970 and 1986 were examined in the Jewish and Bedouin populations. An increase in dizygotic twinning in the whole population, largely due to an increase of rate in the Bedouin population was found. The dizygotic twinning rate in the Bedouin population rose until it reached the level found in the Jewish population. No change with time was found in the monozygotic twinning rates in either population. This suggests that while dizygotic twinning rates are influenced by environmental factors, the monozygotic twinning rates are not. The effects of maternal age and parity on dizygotic and monozygotic twinning rates differed in the two ethnic groups examined. In the Jewish population the dizygotic twinning rate was related to maternal age and parity, while in the Bedouins only maternal age affects the rate. The monozygotic twinning rate has an inverted U shape with maternal age in the Jewish population and is linearly related to maternal age in Bedouin women. No effect of parity on the Jewish monozygotic twinning rate is found but this rate is directly affected by parity in Bedouin women. The effects of maternal age and parity together were examined in both populations. Both maternal age and parity affected the twinning rates; however, the effects are not additive and no interaction between maternal age and parity was found. PMID- 2583339 TI - Miniature electronic blood pressure monitor compared with a blind-reading mercury sphygmomanometer in pregnancy. AB - The use of electronic blood pressure monitors is increasing, but they have received little evaluation in pregnancy. We compared an electronic monitor (Nissei D-175 Digital Monitor) with a London School of Hygiene blind-reading mercury sphygmomanometer in clinical conditions in 41 patients in the third trimester. In 141 comparisons, the electronic monitor read systolic pressures that were 16.53 mmHg higher on average than the mercury sphygmomanometer, the limits of agreement being from -9.13 mmHg to +42.19 mmHg. For diastolic pressures, the electronic monitor read 9.71 mmHg higher on average than the mercury sphygmomanometer, the limits of agreement being from -16.97 mmHg to +36.39 mmHg. The coefficient of repeatability was similar for both instruments with systolic and diastolic readings. As much caution should be exercised with the use of the electronic monitor in late pregnancy as with the mercury sphygmomanometer, and practitioners should be aware of the marked differences that can occur between instruments. PMID- 2583340 TI - Modification of number and of affinity of endometrial EGF receptors during the menstrual cycle. AB - We have analysed the distribution and the binding properties of the epidermal growth factor (EGF) receptor in human endometrium during the menstrual cycle to validate the proposal that steroids affect the growth rate of target cells via growth factor-related pathways. The total number of EGF receptors and their affinity for the iodinate exogenous ligand are significantly higher during the proliferative than the secretory phase; the binding kinetics appear to be hyperbolic and sigmoid during the proliferative and the secretory phase, respectively. These results suggest that endogenous sex steroids can regulate the levels and the properties of EGF receptors in vivo, and support the possibility that receptor-coupled events may play a role in estrogen-stimulated growth. PMID- 2583341 TI - Successful outcome after antepartum expulsion of placenta and fetus into the abdominal cavity; a case report. AB - Spontaneous rupture of the uterus before labour is a rare event associated with a high incidence of maternal and fetal death. We report a case of spontaneous uterine rupture at 34 weeks' gestation in a patient's second pregnancy. The case is unusual because both the mother and baby survived despite the expulsion of the placenta with the fetus into the abdominal cavity prior to laparotomy. PMID- 2583342 TI - Obstetrical problems in patients with Ehlers-Danlos syndrome type IV; a case report. AB - The Ehlers-Danlos syndrome type IV is a heritable connective-tissue disorder characterized by thin translucent skin, pronounced bruising and scarring, and extreme tissue fragility. Obstetrical complications include premature rupture of membranes, rupture of blood vessels and gravid uterus, tearing of perineum, vagina, urethra and bladder, requesting specific prophylactic and therapeutic measurements. Hereditary transmission is usually autosomal dominant with variable expression. Histological examination of skin biopsy and biochemical analysis of collagen proteins from skin fibroblast cultures confirm the clinical diagnosis. DNA studies offer the possibility of prenatal diagnosis in suitable families. The consecutive severe obstetrical complications of a woman with Ehlers-Danlos syndrome type IV are reported here. The patient died at age 33 years from renal artery rupture. PMID- 2583343 TI - Ectopic pregnancies due to contralateral fistulas after sterilization by electrocoagulation; case reports. AB - Three cases of post-sterilization tubal pregnancy are discussed. The sterilizations were performed by bipolar electrocoagulation. The location of the pregnancy was distal to the site of sterilization. There was no continuity between the segment containing the ectopic pregnancy and the uterus. Spermatozoa reached the site of fertilization via a tuboperitoneal fistula. The existence of the fistulas was confirmed by a methylene blue test. In two cases fistulas existed on the contralateral side to the ectopic pregnancy. In the third case, bilateral fistulas were found. So, on performing a salpingectomy for ectopic pregnancy after sterilization failure, we have to be aware of contralateral fistulas. Also good understanding of the mechanism of extra-uterine pregnancy secondary to transperitoneal migration of spermatozoa is important when doing conservative tubal surgery. PMID- 2583344 TI - The oxidative part of the glucose-oxidase reaction. AB - 1. Kinetic parameters of the oxidative part of glucose-oxidase reaction have been measured with 16 different electron-acceptors and glucose as a substrate. 2. In each case, the rate-limiting portion of the oxidative part of reaction was the formation of the E-FADH2.Acceptor-complex; this rate was pH-independent around the pH-optimum of the enzyme. 3. In each case, E-FADH2 acceptor-complex was undetectable in the steady-state kinetics, with the exception of cytochrome-c. 4. The rates of redox reactions between various forms of reduced 5-ethyl-lumiflavin and five different electron-acceptors have been examined with a conventional spectrophotometry. In each case, it was found that the reactions proceeded at high rates whenever thermodynamically feasible, and were totally prevented in the opposite case. 5. Molecular oxygen was able to oxidize only the neutral form of 5 ethyl-1,5-dihydrolumiflavin to its radical form, at a moderate rate; all other forms of reduced 5-ethyl-lumiflavin were not oxidized by O2. 6. By the comparison of enzymatic and model redox reactions, it was possible to establish the minimal mechanism of the oxidative part of the glucose-oxidase catalytic cycle. PMID- 2583345 TI - Molecular mechanisms of gossypol action on sperm motility. AB - 1. Gossypol acetic acid inhibits collective motility of ejaculated ram spermatozoa. 2. Oxygen consumption was stimulated at low gossypol concentrations and inhibited as the concentrations are increased. 3. Gossypol inhibits respiration of permeabilized spermatozoa supported by durohydroquinome, which indicates a direct inhibition of mitochondrial electron transport chain. 4. The rapid reduction of mitochondrial dependent motility, high uncoupling effect and almost complete inhibition of mitochondrial calcium accumulation, indicate that gossypol inhibits motility in a mechanism by which mitochondrial uncoupling is involved. PMID- 2583346 TI - Prooxidant and antioxidant effects of ascorbate on tBuOOH-induced erythrocyte membrane damage. AB - 1. t-Butylhydroperoxide (tBuOOH) a lipoperoxide analog, causes rapid and considerable sulphydryl (SH) oxidation but almost no lipid peroxidation in red blood cell membranes (ghosts) containing no detectable haemoglobin. 2. tBuOOH, in the presence of ascorbate, produces significant lipid peroxidation the level of which is proportional to the ascorbate concentration. The initiation of lipid peroxidation is thought to occur by the reactive tBuO (butoxyl) species via the reductive decomposition of tBuOOH by ascorbate. 3. Ascorbate protects ghost membranes from the tBuOOH-induced SH oxidation in a dose-dependent fashion. 4. There is no parallelism between lipid peroxidation and SH oxidation in these systems. This suggests that the two processes occur independently of each other. 5. These findings indicate that, simultaneously, ascorbate can have both a protective and a prooxidant action in different membrane components under the same oxidative stress. PMID- 2583347 TI - Characterization of the terminal cisternae and longitudinal tubules of sarcoplasmic reticulum from malignant hyperpyrexia susceptible porcine skeletal muscle. AB - 1. The sarcoplasmic reticulum (SR) from malignant hyperpyrexia susceptible (MHS) and control porcine skeletal muscle was separated into vesicular fractions enriched in the membrane elements of the terminal cisternae and longitudinal tubules. 2. The two membrane preparations were highly purified and had distinctive features which were associated with their origins in the SR membraneous network. 3. Calsequestrin and calcium were enriched in the terminal cisternae fraction (HSR), in comparison to longitudinal tubule preparations (LSR). 4. The HSR membrane also had a greater total capacity to store Ca2+ and Ca2+ release was more rapid than from LSR preparations. 5. No distinction could be made between the membrane morphology, Ca2+ -fluxes or Ca2+ -dependent ATPase activities, associated with these functionally distinct regions of MHS and control preparations. PMID- 2583348 TI - Effect of the administration of cycloheximide to thioacetamide-primed rats or partial-hepatectomized rats on the RNA polymerase I activity in isolated nuclei of liver. AB - 1. Twenty-four hours after administration of thioacetamide to normal rats, the activity and amount of RNA polymerase I in isolated liver nuclei were almost doubled. 2. When cycloheximide was administered to the drug-treated rats and normal rats 1 or 2 hr before death, the reduction in the activity was of the same degree, that is, about half of the activity of liver nuclei from normal rats. 3. Partial hepatectomy also caused about 2-fold increase in the RNA polymerase I activity in isolated liver nuclei after 16 hr, but the increased activity was almost completely abolished by injection of cycloheximide 1-3 hr before killing. PMID- 2583349 TI - Sphingomyelin and ceramide: phosphoethanolamine synthesis in ram spermatozoa plasma membrane. AB - 1. The possibility for sphingomyelin and ceramide: phosphoethanolamine synthesis in ram spermatozoa plasma membranes has been established. 2. Ceramide: phosphoethanolamine formation appears to be higher than the synthesis of sphingomyelin. 3. The pH optimum of the phosphatidylethanolamine: ceramide phosphoethanolamine transferase is about 7.0. An inhibition of its activity was observed in the presence of Ca2+ and Zn2+ ions. PMID- 2583350 TI - Cloning and sequencing of a cDNA encoding the precursor to the 24 kDa iron-sulfur protein of human mitochondrial NADH dehydrogenase. AB - 1. We have isolated a cDNA encoding the 24 kDa subunit, an iron-sulfur protein, of mitochondrial NADH dehydrogenase from a human fibroblast cDNA library by colony hybridization using a rat 24 kDa subunit cDNA as a probe. 2. The presequence predicted from the human cDNA sequence is typical of precursors to mitochondrial proteins in a high content of basic residues and in the absence of acidic ones. 3. The mature form of the human 24 kDa subunit shows 95% homology with its rat counterpart. Five cysteine residues are conserved among human, rat and bovine; four of these are expected to be involved in the binding of a binuclear iron-sulfur cluster. PMID- 2583351 TI - Ornithine decarboxylase in resting human mononuclear leucocytes: evidence for an endogenous inhibitor. AB - 1. Ornithine decarboxylase (ODC) was measured in human mononuclear leucocytes (HML) by retention of putrescine on cation exchange paper. 2. The method was validated with unstimulated HML, phytohemagglutinin-stimulated HML, and a commercial preparation of ODC. The average enzyme activity of unstimulated HML (50 samples) was 22.6 +/- 7.3 pmol/hr 10(7) cells, with 29 values less than 5 pmol/hr 107 cells. 3. The results show that an endogenous inhibitor or inactivator of ODC exists in unstimulated HML: enzyme activity in extracts of mitogen-stimulated cells were inhibited by extracts of unstimulated cells (37 55%) inhibition under the conditions used. PMID- 2583352 TI - Exercise-induced lipid peroxidation and leakage of enzymes before and after vitamin E supplementation. AB - 1. The purpose of this study was to investigate the effects of vitamin E on serum levels of malondialdehyde following the acute exhaustive exercise in human, and to determine whether the magnitude of leakage of enzyme would be affected by vitamin E supplementation. 2. Increase of malondialdehyde after exercise before vitamin E supplementation was slight (but statistically significant), however after supplementation with vitamin E, malondialdehyde level after exercise was significantly decreased. 3. Leakage of enzyme was significantly increased after exercise before vitamin E supplementation, but it was lower following exercise after vitamin E supplementation. 4. Lipid peroxidation following a bout of acute heavy exercise can be inhibited by vitamin E supplementation. PMID- 2583353 TI - Circular dichroic study of the conformational stability of sulfhydryl-blocked bovine serum albumin. AB - 1. The blockage of the single sulfhydryl-group of bovine serum albumin does not alter the secondary structure, although the alpha-helical structure is destabilized since lower concentrations of guanidine and of urea unfold the protein. 2. What happens to the previously helical structure depends upon the reagent used to block the sulfhydryl-group. Bovine serum albumin derivatized with 5,5'-dithiobis-(2-nitrobenzoic acid) and iodoacetate preferentially acquire the beta-structure in high concentrations of guanidine and urea, whereas iodoacetamide-derivatized bovine serum albumin acquires primarily the random coil structure. 3. Part of the helical structure is also lost in 5-6 mM sodium dodecyl sulfate; thionitrobenzoate-bovine serum albumin shows an increase in the random coil, whereas the two alkylated proteins display the increase both in beta structure and random coil. 4. Carboxymethylation or carboxamidomethylation of fully reduced bovine serum albumin results in a drastic change in the secondary structure of the protein with a substantial decrease in alpha-helix and a corresponding increase in both beta-structure and random coil. These extensively alkylated proteins also display differences in denaturation profiles in solutions of guanidine and urea. PMID- 2583354 TI - Purification and properties of the thrombin-like enzyme from the venom of Lachesis muta muta. AB - 1. The coagulating enzyme of the Lachesis muta muta venom was purified to homogeneity by a combination of a gel filtration in Sephadex G-100 and affinity chromatography on agarose-agmatine resin. 2. Several forms of the enzyme were prepared by isoelectric focusing with pIs ranging from 3.1 to 5.0; the asialoenzyme focused as a narrow band at pH 8.7. SDS-PAGE analysis of the purified enzyme revealed a single broad band with apparent Mr of 41-47 kDa. 3. The enzyme cleaves only fibrinopeptide A from fibrinogen; it does not activate factor XIII and is devoid of kallikrein-like activity. 4. Kinetic properties of the enzyme were determined for representative synthetic chromogenic substrates and inhibitors. PMID- 2583355 TI - Growth-related changes of non-histone chromatin proteins from Kirkman-Robbins hepatoma. AB - 1. Non-histone chromatin protein fractions NHCP1 and NHCP2 eluted from hydroxyapatite with 50 and 100 mM phosphate buffer (pH 6.8) from nuclei of Kirkman-Robbins hepatoma from 4th, 7th and 9th day of growth were analysed by one and two-dimensional gel electrophoresis as well as Western blot technique in the presence of antibodies elicited against NHCP1, NHCP2 and dehistonized chromatin of hamster hepatoma and liver. 2. The presence of electrophoretically and immunologically specific components among NHCP1 and NHCP2 fractions during Kirkman-Robbins hepatoma growth was stated. PMID- 2583356 TI - Regulation of lipid metabolism by dipyridamole and adenosine antagonists in rat adipocytes. AB - 1. Acute effects of dipyridamole, an inhibitor of adenosine transport, direct activators of adenylate cyclase and thirteen adenosine antagonist analogs on fatty acid synthesis have been examined in terms of the control of [1-14C]acetate incorporation into labeled fatty acids in the presence of glucose. 2. This monosaccharide acts as a stimulator of lipogenesis by generating NADPH for the lipid synthesis. 3. The relationship between lipogenesis and lipolysis was compared with a variety of adenylate cyclase stimulators. 4. The data obtained reveals that dipyridamole potentiated the inhibitory or stimulatory effects of isoproterenol and forskolin on lipogenesis and on lipolysis, respectively. 5. In these cases the data show that it exists an inverse relationship between lipogenesis and lipolysis. 6. Dipyridamole and methylxanthine analogs only moderately affect the rate of lipolysis whereas its effects are more potent on lipogenesis and lend further support to the hypothesis that dipyridamole antagonize adenosine actions as well as methyl xanthines. 7. These results suggest that dipyridamole and adenosine antagonists alter lipogenesis independently of the lipolytic process and that it exists an inverse relationship between lipogenesis and lipolysis under some conditions whereas there are not under others. PMID- 2583357 TI - Activation of rat liver S-adenosylmethionine decarboxylase by putrescine and 2 substituted 1,4-butanediamines. AB - 1. The activation of S-adenosyl-L-methionine decarboxylase (SAM-DC) by putrescine and a series of 1,4-butanediamines with a substituent in position 2 was studied. 2. Kinetic data show the activation of SAM-DC by putrescine is essentially uncompetitive. 3. All 2-substituted 1,4-butanediamines were activators, although not as potent as putrescine itself. 4. At high concentrations of SAM activation of SAM-DC by putrescine and putrescine analogs deviated considerably from uncompetitive activation kinetics. 5. In order to explain the experimental data, especially the non-linearity of the "fractional velocity plots", it was necessary to postulate two independent, but equivalent activator binding sites, for which substrate (SAM) and activator compete. 6. Based on this kinetic model an equation was derived which describes the rate of SAM decarboxylation as a function of substrate and activator concentrations. 7. From the simulated curves, approximate values for equilibrium constants for the binding of activator and substrate to the activator binding sites, and relative rate constants for the product forming steps were calculated. 8. Even a minor change of the structure, such as the substitution of one hydrogen atom by fluorine in the 2-position of putrescine had a very considerable effect on the potency of activation. 9. It is apparent that the structural requirements of an activator of SAM-DC are highly specific. PMID- 2583358 TI - Skeletal muscle mitochondrial respiration of malignant hyperthermia-susceptible patients. Ca2+-induced uncoupling and free fatty acids. AB - 1. Skeletal muscle mitochondria of malignant hyperthermia (MH)-susceptible patients showed normal oxidative phosphorylation but were more easily uncoupled than normal by exogenous Ca2+. 2. Fatty acids, in stimulating the mitochondrial ATPase activity, are responsible for the enhanced State 4 respiration in MH susceptible patients. 3. These results imply that skeletal muscle mitochondria and free fatty acids are associated with the development of MH syndrome. PMID- 2583359 TI - Antimetabolic activity of L-ascorbic acid in human and animal tumors. AB - 1. The effect of high concentrations of L-ascorbic acid on the growth of some human and animal transformed and non-transformed cell lines has been investigated. Directly implemented into culture of transformed cell lines it decreased [3H]thymidine, [3H]uridine and [3H]leucine incorporation into cells. Vitamin C inhibited DNA synthesis by transformed cells 3-4 times more efficiently than by normal cells. 2. In vivo treatment of athymic nude mice bearing human mammary carcinoma with 500 mg/kg L-ascorbic acid for the first 15 days markedly inhibited the growth of tumor cells. 3. As determined by alkaline elution, both DNA strand breaks and DNA cross links were observed in mammary carcinoma cells treated with vitamin C. DNA-DNA and DNA-protein cross links in cells treated with L-ascorbic acid were revealed by the proteinase K assay. Removal of vitamin C caused an immediate onset of spontaneous repair of single or double stranded DNA breaks. If, however, vitamin was reintroduced into cell culture, this spontaneous repair was reversed. 4. Our results indicate an antimetabolic activity of L ascorbic acid in human and animal transformed cells, probably due to lethal damages in DNA. PMID- 2583360 TI - Maximal activities of key enzymes of glutaminolysis, glycolysis, Krebs cycle and pentose-phosphate pathway of several tissues in mature and aged rats. AB - 1. The maximum activities of some key enzymes, which provide a quantitative indices of flux through several important pathways have been measured in brain, liver, muscle, white and brown adipose tissue and lymphocytes of mature and aged rats. 2. The results were expressed as mumol/min per g fresh weight and nmol/min per mg protein. 3. On the both basis, as compared to mature rats, hexokinase activity is decreased in brown adipose tissue and increased in soleus muscle. 4. Glucose-6-phosphate dehydrogenase activity is decreased in most tissues and increased in brain. 5. Citrate synthase activity, which provides a qualitative index of the Krebs cycle, is decreased in white adipose tissues and lymphocytes. 6. Glutaminase activity is decreased in brain, white and brown adipose tissues but is increased in lymphocytes. PMID- 2583362 TI - Evidence that Y-organs of the crab Cancer antennarius secrete 3-dehydroecdysone. AB - Y-organs are paired glands in crustaceans that secrete a class of steroid hormones (ecdysteroids) that regulate growth, molting and development. The glandular secretion has been assumed to be solely the ecdysteroid, ecdysone, a polyhydroxylated derivative of cholesterol. We previously reported that Y-organs of a crab (Cancer antennarius) additionally secreted an ecdysteroid that is less polar than ecdysone. Evidence is presented here that the other secretion product is 3-dehydroecdysone (3-dhE). The compound co-chromatographed with authentic 3 dhE in both normal-phase, and reversed-phase, high-performance liquid chromatography. Mass spectrometry of the ecdysteroid gave results consistent with its identity as 3-dhE. The putative 3-dhE was radiolabeled by injecting crabs with [3H]cholesterol and then incubating the Y-organs. The putative [3H]3-dhE secretion was then subjected to chemical reduction. The reaction yielded labeled products that co-chromatographed with authentic ecdysone and 3-epiecdysone. Results of other experiments gave the following results: (1) Putative 3-dhE was not altered (chromatographic criteria) by incubations with snail hydrolases. (2) Putative [3H]3-dhE, added to incubations of Y-organ halves or homogenates, was not significantly converted to ecdysone; also, no conversion was evident after incubation in medium alone in which the hemolymph serum supplement was raised to 50% of the volume. (3) [3H]Ecdysone was not converted to putative 3-dhE in vitro by Y-organ halves or homogenates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583361 TI - Estradiol receptor in the lizard liver (Podarcis s. sicula). Seasonal changes and estradiol and growth hormone dependence. AB - This study shows that in the liver of the oviparous lizard, Podarcis s. sicula, the estrogen receptor (ER) level increases during the reproductive period (spring) when vitellogenesis occurs. This phenomenon interested both unfilled and filled ER present in the cytosolic and nuclear fractions. The increase in unfilled cytosolic and filled nuclear receptor was positively correlated to the plasma level of vitellogenin. The level of liver ER approximated that of mammalian liver ER and, therefore, it is higher than that reported for the liver of several nonmammalian species. At electrofocusing, liver ER distributes in two pH ranges (pH 6.5-7.5 and 8.0-8.8, respectively). The first form predominated in nuclei of reproductive females or of spayed estrogenized females and could represent the activated form of receptor. Ovariectomy was followed by a decrease in liver ER which can be induced in spayed females by estradiol administration. Pituitary growth hormone (GH) seemed to exert a synergic effect on estradiol liver estrogen receptor regulation. In lizards treated both with estradiol and GH, in fact, there was a significant increase in nuclear filled ER rather than an increase in the level of total nuclear ER. PMID- 2583363 TI - Alkali-resistant protein phosphorylation and tyrosine kinase activity of epithelial cell types from normal and metaplastic canine prostates. AB - To determine how functional changes such as growth and differentiation in the prostatic epithelium would alter protein phosphorylation on tyrosyl residues, differentiated (secretory) and basal (non-secretory) prostatic epithelial cells from normal and from metaplastic canine prostates were labeled with [32P]phosphate and their alkali-resistant phosphoproteins were analyzed by autoradiography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The tyrosine protein kinase activity of the cells was also assayed by phosphorylation of a synthetic substrate, poly(Glu80-NaTyr20), in the presence of [gamma-32P]ATP. The prostates were characterized by tissue morphology and the cells by their density on Percoll gradients and [3H]thymidine incorporation into DNA. In prostates from intact dogs, tall columnar secretory epithelial cells were predominant and the non-secretory or basal epithelial cells were quiescent and did not incorporate [3H]thymidine. In metaplastic glands obtained from estrogen treated castrated dogs, most of the isolated cells were non-secretory and synthesized DNA. Alkali-resistant phosphoproteins were present in all cell types. Except for two common phosphoproteins, p44 and p82, the relative phosphoprotein distribution within the gel differed when normal prostatic cells were compared to the metaplastic cells. However, the phosphoprotein patterns were the same in secretory and non-secretory cells from the same prostate tissue. On the other hand, the relative labeling intensity of phosphoproteins was always higher in non secretory cells compared to corresponding secretory cells. Accordingly, tyrosine protein kinase (TPK) activity, expressed on a cell basis, was also higher in non secretory cells; the ratios of TPK activities, non-secretory over corresponding secretory cells, was always higher than unity for all preparations but overlapped when cells from metaplastic glands were compared to those isolated from normal prostates. Thus, non-secretory epithelial cells isolated from either normal or metaplastic glands have a higher ability than corresponding secretory cells to phosphorylate endogenous alkali-resistant phosphoproteins and their TPK activity, measured with the synthetic substrate poly(Glu80-NaTyr20), is also higher. PMID- 2583365 TI - 18-Hydroxylase activity in the Y1 adrenal cell line. AB - 18-Hydroxylase activity, reported here for the first time in the mouse adrenal tumor cell line (Y1), was expressed in the metabolism of 11-deoxycorticosterone (DOC) and corticosterone (B). Detected after 24 h of incubation, it was more evident after 48 h and produced mostly 18-hydroxy-20 alpha-DHB from these exogenous substrates. However, 18-hydroxylation was quantitatively less significant than the metabolism of 20 alpha-reduction and 11 beta-hydroxylation (of DOC). The latter is also the predominant metabolism of progesterone in this cell line, during the conversion of cholesterol from the serum-supplemented culture media. The cytochrome P-450 11 beta activity of the Y1 cells is similar to that of the mouse in vivo which catalyzes the production of an 11 beta 18 dihydroxylated metabolite as the principal 18-hydroxylated steroid. It is different from that of other species, such as the rat and the bovine, both in terms of the ratio of 11 beta- to 18-hydroxylated metabolites and of the structure of these metabolites. PMID- 2583364 TI - Dexamethasone control of growth hormone mRNA levels in GH3 pituitary cells is cycloheximide-sensitive and primarily posttranscriptional. AB - To clarify the mechanism of growth hormone (GH) gene activation by glucocorticoids in GH3 pituitary cells, GH mRNA accumulation in nuclear and cytoplasmic compartments was measured in the presence and absence of cycloheximide. In dexamethasone-treated cells, levels of GH mRNA were increased in the nucleus by 6 h and in the cytoplasm by 12 h. Dexamethasone treatment caused a 5- to 24-fold rise in total GH mRNA levels by 48-72 h. The differential elevation of nuclear levels of GH mRNA relative to the amount of cytoplasmic GH mRNA persisted for 48 h. A transient accumulation of GH mRNA in the nucleus was followed by a brief rise in cytoplasmic GH mRNA levels in GH3 cells treated simultaneously with dexamethasone and cycloheximide. In GH3 cells pretreated for 2 h with cycloheximide, the rise in nuclear and cytoplasmic GH mRNA levels mediated by dexamethasone was blocked completely. Levels of glucocorticoid receptor were unaffected by cycloheximide. These data suggest that the stimulation of GH mRNA levels by glucocorticoids is initiated within the nucleus and that cycloheximide-sensitive events are essential for this stimulation to occur. To assess the importance of GH gene transcriptional activation by glucocorticoids, nuclear transcription run-on reactions and assays of GH promoter activity in an aminoglycoside 3'-phosphotransferase (Neo) fusion gene within stably transformed GH3 cells were performed. Evidence for a weak, transient transcriptional activation of the GH gene by dexamethasone in nuclear run-on assays was obtained. Consistent with this idea, a 30-72 h exposure to dexamethasone raised levels of Neo mRNA in GH-Neo GH3 cell transformants by less than or equal to 2-fold. We conclude that glucocorticoid stimulation of GH mRNA in GH3 cells requires ongoing protein synthesis and can occur largely independently of GH gene transcriptional activation. PMID- 2583366 TI - Differential responses of pituitary kallikrein and prolactin to tamoxifen and chlorotrianisene. AB - Glandular kallikrein, a trypsin-like serine protease, and prolactin (PRL) are both estrogen-induced proteins in rat anterior pituitary lactotrophs. The estrogen agonist and antagonist effects of tamoxifen (TAM, a triphenylethylene antiestrogen) and chlorotrianisene (TACE, a triphenylethylene estrogen) on anterior pituitary glandular kallikrein and PRL were examined to see if TAM and TACE differentially affect these estrogen response of lactotrophs after in vivo dosing of rats. TAM and TACE acted as partial agonists on PRL and uterine weight induction. In contrast, on glandular kallikrein induction TAM acted as a pure estrogen antagonist and TACE acted as an almost pure antagonist. The results document that both TAM and TACE exhibit protein-specific estrogen agonist and antagonist efficacies in lactotrophs, with the estrogen induction of glandular kallikrein being particularly sensitive to antagonism by TAM in vivo. The marked antiestrogen character of TACE was surprising since TACE has been classified and clinically used as an estrogen. PMID- 2583367 TI - Structural and functional polarity of starfish blastomeres. AB - The cortex of the blastomeres of Asterina pectinifera are structurally polarized so that some kinds of granules in the cortex, which can be stained vitally with Nile blue (Nile blue-positive granules, NBGs), and microvilli were distributed mainly in the apical region. The blastomeres always faced the adjoining blastomeres and blastocoel with the NBG-free, smooth region during embryogenesis. To confirm whether such blastomeres are functionally polarized, we rotated one of the blastomeres in the 2-cell-stage embryo so that it faced the other with the NBG-containing region. As a result, all embryos developed into twin or partitioned blastulae. This shows that the blastomeres are functionally polarized and have to orient the basal cortex toward the inner side of the embryo in order to be integrated into a blastula together with the others. The cortical polarity was formed and maintained even in blastomeres of dissociated embryos. In such blastomeres the cleavage furrows were formed along the axis of polarity. When the blastomeres began to adhere closely to each other at the 256-cell stage, only the NBG-free (basal) region acquired adhesiveness. These facts make it possible to infer why the correct apicobasal orientation of blastomeres is necessary for embryonic integration, without considering intercellular communication during the cleavage stage. PMID- 2583368 TI - Involvement of microtubules and microfilaments in the control of the nuclear movement during maturation of mouse oocyte. AB - We confirm that the centrifugal migration of the chromosomes in maturing mouse oocytes depends on a microfilament-mediated process. We investigated the role of the cytoskeleton in the germinal vesicle (GV) behavior of oocytes prevented from resuming meiosis by either activators of protein kinase A or activators of protein kinase C. A time-lapse microcinematography study demonstrates that GV immobilization by isobutylmethylxanthine (IBMX) is overcome by colcemid (COL), nocodazole (NOC), and taxol and that cytochalasin D (CCD) reversibly immobilizes the GV of oocytes treated with either IBMX + COL (or NOC) or 12-O tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, known to allow a programmed GV cortical translocation. An immunofluorescence analysis shows that the disorganization of a perinuclear microtubule network is the very first cytological clue of maturation. IBMX promotes its persistence while NOC, COL, and taxol induce its immediate disappearance. It is concluded that elements of the cytoplasmic microtubular complex (CMTC) are passively involved in the control of the setting up of a "centrifugal displacement property" (CDP) by counteracting a motive force provided by the microfilament cytoskeleton. Finally, TPA induces a clearcut reorganization instead of a total disorganization of the CMTC. This reorganization is, however, sufficient to allow the microfilaments to drive the GV displacement. PMID- 2583369 TI - Parthenogenesis in Xenopus eggs injected with centrosomes from synchronized human lymphoid cells. AB - In Xenopus eggs, normal development requires the participation of the centrosome provided by the sperm. Injection of foreign centrosomes purified from exponentially growing mammalian cells enables the eggs to undertake parthenogenesis. In order to know whether such a complementation required centrosomes already committed to duplication, we have prepared centrosomes from human cells synchronized at different stages of the cell cycle (G0, G1, G2). We show that the three types of centrosome possess a similar parthenogenetic activity and conclude that duplication of heterologous centrosome can be triggered in Xenopus eggs. PMID- 2583370 TI - The responses of pollen to applied electrical fields. AB - The growing pollen tubes of tomato and tobacco were exposed to electrical fields and the effect on the direction of growth was measured. They responded by turning toward the positive electrode (anode) and gave a detectable response in fields as small as 0.1 mV/tube diameter. The sites of germination of tobacco pollen grains were also affected by applied fields; the pollen tubes tended to emerge from the anodal side. This effect was detectable at a field of 0.4 mV/grain diameter. PMID- 2583371 TI - Local shifts in position and polarized motility drive cell rearrangement during sea urchin gastrulation. AB - This study examines the mechanisms of epithelial cell rearrangement during archenteron elongation in the sea urchin embryo using scanning electron microscopy, differential interference contrast videomicroscopy, cell marking, and fluorescently labeled chimaeric clones. Archenteron elongation involves two major processes: local shifts in position of cells in the archenteron wall and polarized motility of the cells as they rearrange. Fluorescently labeled chimaeric clones introduced into the archenteron of Lytechinus pictus are initially 4-5 cells wide; by the end of gastrulation the clones elongate and narrow, so that they are one cell wide in the narrowest region of the archenteron. The extent of clonal mixing indicates that cells in the archenteron change their relative positions by only 1-2 cell diameters during cell rearrangement. Cells at the blastopore rearrange concomitantly with cells in the archenteron, resulting in a 35% decrease in blastopore diameter. Endoderm cells undergo polarized, stage-specific changes in shape and motility as they rearrange; (1) they flatten markedly along their apical-basal axis throughout archenteron elongation; (2) just prior to the onset of cell rearrangement, basal surfaces of all cells in the archenteron extend long, polarized lamellipodial protrusions along the axis of extension of the archenteron; (3) as cell rearrangement begins, basal surfaces round up and the cells become isodiametric; (4) by the 3/4 gastrula stage the cells become stretched along the animal-vegetal axis, apparently due to filopodial traction, and finally (5) they continue to rearrange, returning to a less elongated shape by the end of gastrulation. Direct observation of gastrulation in the cidaroid Eucidaris tribuloides indicates that in this species cell rearrangement is accomplished by progressive circumferential intercalation of cells without upwardly directed filopodia. This intercalation is accompanied by explosive, apparently stochastic, cortical blebbing activity at the boundaries between cells, suggesting that in addition to whatever cell rearrangement may be generated by filopodial tension, such activity is an important component of the active rearrangement process. PMID- 2583372 TI - The establishment of polarity by hippocampal neurons: the relationship between the stage of a cell's development in situ and its subsequent development in culture. AB - Neurons removed from the embryonic hippocampus and placed into culture develop structurally and functionally distinct axonal and dendritic processes. The central issue addressed in this study concerns the extent to which the sequence of events which results in the differentiation of neurites by hippocampal neurons in culture is influenced by the cell's state of development in situ. [3H]thymidine was administered to pregnant rats either on Embryonic Day 15 (E15) or on E18.5 to label hippocampal neurons at known stages of their development. All fetuses were sacrificed on E19. Some of the fetal brains were sectioned and examined by autoradiography to determine the location of labeled cells in the hippocampus. The remaining brains were used to prepare hippocampal cell cultures. Neurons labeled at E18.5 remained confined to the ventricular zone at E19. Those labeled at E15 had completed their migration to the cortical plate. Other data suggest that the former cells had not yet initiated process outgrowth, while the latter cells had begun to elaborate both axons and dendrites. When introduced into culture, both populations of cells developed axons and dendrites and both compartmentalized MAP2 to the dendritic domain. Moreover, despite marked differences in their developmental state at the time of introduction into culture, both underwent the same sequence of developmental events leading to axonal and dendritic development. In a few cases cells that incorporated [3H]thymidine in situ at E18.5 apparently underwent mitosis in culture. These neurons also developed axons and dendrites appropriately. These results indicate that hippocampal neurons become polarized in culture, even if they have never developed axons or dendrites in situ, and do so as efficiently as cells that have become polarized before being placed into culture. Moreover, they indicate that the same sequence of events leading to the establishment of polarity occurs for hippocampal neurons with different developmental histories prior to culturing. PMID- 2583373 TI - Induction of reinitiation of meiosis in amphibian Bufo oocytes by injection of ciliate Paramecium extracts. AB - Germinal vesicle breakdown (GVBD) of amphibian Bufo oocytes can be induced if Paramecium extracts were injected into them. The activity of meiosis-reinitiation inducing factor (MRIF) appeared in premeiotic G1 cells, then the activity fluctuates according to the degrees of micronuclear chromatin condensation in meiosis. Proliferating micronucleate and amicronucleate cells also showed the same activity. MRIF differed from MPF (M phase promoting factor), because MRIF appeared not only in M phase cells but also in premeiotic interphase cells and its action on the induction of GVBD was inhibited by cycloheximide. Preliminary experiments showed that MRIF was a heat-labile soluble protein. PMID- 2583374 TI - Gastrulation in the sea urchin is accompanied by the accumulation of an endoderm specific mRNA. AB - Spatial diversification of the endoderm during gastrulation in the sea urchin Lytechinus variegatus was examined with an endoderm-specific cDNA clone. This cDNA clone, LvN1.2, was identified by a differential cDNA screen between the ectoderm and endoderm/mesoderm fractions from prism stage embryos. The LvN 1.2-kb mRNA was first detectable by Northern blots at the mesenchyme blastula stage just prior to gastrulation and then accumulated approximately 15-fold from gastrulation to the pluteus stage. In situ hybridization analysis demonstrated that the mRNA accumulated specifically in endoderm and was restricted to the hindgut-midgut regions. This restricted localization was apparent during gastrulation and predicted the morphological distinction between foregut and midgut eventually seen at prism and pluteus stages. Sequence analysis showed that the 189-amino acid open reading frame represented a novel protein. In vitro translation of synthetically produced LvN1.2 mRNA and Western blot analysis with antibodies to the protein sequence yielded the same 25-kDa polypeptide on SDS PAGE. The LvN1.2 protein resided within discrete granules of the hindgut and midgut cells. These particles were concentrated to the luminal aspect of the cells, suggesting the LvN1.2 protein participates in the digestive function of this region of the gut. PMID- 2583375 TI - Mouse oocytes gradually develop the capacity for activation during the metaphase II arrest. AB - Metaphase II (M II) mouse oocytes were subjected to a parthenogenetic stimulus (8% ethanol) or fertilized in vitro at various times following the extrusion of the first polar body. The oocytes progressively develop the ability for full activation. Their responsiveness to activation stimuli not only increases, but also changes qualitatively with time. Newly arrested oocytes do not respond at all; then, when the ability to undergo meiotic anaphase II first develops, the response is defective: following extrusion of the second polar body (II PB), the oocyte does not enter interphase but arrests again at metaphase (M III-arrest). Finally, oocytes gain the ability for full activation including the entry to interphase. Depending on the type of activating stimulus, oocytes exhibit the capacity for full activation at different ages. The oocyte arrest in M III is similar to M II and can be released by subsequent activation. Such oocytes undergo anaphase III, extrude a third polar body (III PB), and form an aneuploid female pronuclei. PMID- 2583376 TI - A monoclonal antibody against an adult-specific cuticular protein of Tenebrio molitor (Insecta, Coleoptera). AB - To study the sequential expression of the epidermal program in the mealworm Tenebrio molitor, monoclonal antibodies were prepared against the water-soluble proteins from preecdysial adult cuticle. Among the 16 clones obtained, one of them (named K2F6) recognized a 20-kDa antigen, found only in adult extracts but not in the larval or pupal ones, as revealed by immunoblot analysis. Our results strongly suggest an epidermal origin for this protein. The monoclonal antibody K2F6 fails to react with water-soluble proteins from fat body and hemolymph taken during the deposition of the 20-kDa antigen. Electron microscopic immunogold localization of this antigen showed that it is secreted, just after epicuticle deposition, in the 30 first-deposited preecdysial lamellae of sternal and elytral cuticles only. The sclerotizing process, which modifies the physicochemical properties of these cuticles, does not prevent the immunoreaction. When the expression of the adult program was inhibited by application of a juvenile hormone analog (ZR 515), the water-soluble proteins from different pupal-adult intermediates were never recognized by the monoclonal antibody K2F6 using immunoblot analysis. These results support the conclusion that this 20-kDa antigen is a protein specific for the sclerotized cuticle of the adult stage. PMID- 2583377 TI - Degradation of hyaluronic acid does not prevent looping of the mammalian heart in situ. AB - It is currently proposed that accumulation of hyaluronic acid (HA) and subsequent hydration of the cardiac extracellular matrix is required for normal looping of the vertebrate heart. To test this hypothesis, we cultured Wistar rat embryos (Gestational Day 9.5) in rat serum plus 20 TRU/ml of Streptomyces hyaluronidase (treated embryos) or rat serum alone (control embryos). Despite degradation of HA as documented by Alcian blue staining at pH 2.5, 57 of 59 treated embryos developed normally looped hearts after 36 hr in culture. These experiments suggest that the accumulation of HA is not required for normal looping of the mammalian heart in situ. PMID- 2583378 TI - Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes. AB - Erythrocytes of diabetic patients have abnormal membrane properties. We examined in vivo membrane lipid peroxidation in erythrocytes of diabetic subjects and its possible relationship with hyperglycemia. Lipid peroxidation was assessed in fresh, untreated erythrocytes by quantitating thiobarbituric acid reactivity and an adduct of phospholipids and malonyldialdehyde (MDA), an end product of lipid peroxidation, with thin-layer chromatography of lipid extract of diabetic erythrocytes. There was a significantly increased membrane lipid peroxidation in diabetic erythrocytes compared with nondiabetic erythrocytes. The degree of membrane lipid peroxidative damage in erythrocytes was significantly correlated with the level of glycosylated hemoglobin, an index of mean glucose level for the preceding 3-4 mo. This suggests that peroxidation of membrane lipids and accumulation of MDA occurs in erythrocytes of diabetic patients. PMID- 2583379 TI - Prevalence and risk factors for micro- and macroalbuminuria in diabetic subjects and entire population of Nauru. AB - Rates of elevated urinary albumin concentration, defined as microalbuminuria (30 299 micrograms/ml) and macroalbuminuria (greater than or equal to 300 micrograms/ml), were determined on random morning urine specimens in the population of Nauru, which has a high prevalence of non-insulin-dependent diabetes mellitus. The prevalence of elevated urinary albumin levels in the total Nauruan population was very high: 26 and 30% of men and women, respectively, had microalbuminuria, whereas 13% of both sexes had macroalbuminuria. Of the subjects with macroalbuminuria, 66% had diabetes. The prevalence increased with worsening glucose tolerance; 26% of subjects with normal glucose tolerance had either micro or macroalbuminuria, increasing to 43% of subjects with impaired glucose tolerance, 63% of newly diagnosed diabetic subjects, and 75% of previously diagnosed diabetic subjects. Associations between elevated urinary albumin concentration and putative risk factors were assessed for both the total population (n = 1184) and the diabetic subgroup alone (n = 318). Fasting plasma glucose and hypertension were the most important independent correlates for the whole population, whereas plasma creatinine was also important in diabetic subjects. Age at onset and duration of diabetes were not found to be significantly associated with elevated albumin concentration. In subjects with normal glucose tolerance, hypertension and hyperuricemia were the most important associated factors. These results suggest that blood glucose, blood pressure, and possibly obesity and plasma uric acid are important modifiable risk factors for both micro- and macroalbuminuria in this population. PMID- 2583380 TI - Rapid detection of IDDM susceptibility with HLA-DQ beta-alleles as markers. AB - The allelic forms of the human leukocyte antigen (HLA)-DQ beta-chain (DQB1) have been recognized as the best markers of insulin-dependent diabetes mellitus (IDDM) susceptibility. We describe a method that allows the recognition of these DQB1 alleles without the use of either allele-specific oligonucleotide probes or radioactive material. This method determines these alleles by electrophoretically separating restriction enzyme-generated fragments from the polymerase chain reaction-amplified second exon of the HLA-DQB1 gene, which encodes the first domain of the protein chain. This digestion method, which is simpler and more rapid than the previously adopted hybridization method, is described in detail to enable individuals at any clinical laboratory to quickly ascertain IDDM susceptibility. PMID- 2583381 TI - Evaluation of WHO and NDDG criteria for impaired glucose tolerance. Results from two national samples. AB - The considerable disagreement in the definition of impaired glucose tolerance (IGT) by National Diabetes Data Group (NDDG) and World Health Organization (WHO) criteria was explored in two independent representative adult population samples in Israel (n = 1119) and the United States (n = 1783). Five categories of nondiabetic glucose tolerance were defined according to fasting plasma glucose (FPG) values (mM) and 1- and 2-h plasma glucose values (PG1 and PG2, respectively) after oral glucose load: 1) normal by WHO and NDDG (FPG less than 6.4 mM, PG1 less than 11.1 mM, PG2 less than 7.8 mM), 2) Normal by WHO, nondiagnostic by NDDG (FPG 6.4-7.7 mM, PG1 less than 11.1 mM, PG2 less than 7.8 mM), 3) normal by WHO, nondiagnostic by NDDG (FPG less than 7.8 mM, PG1 greater than or equal to 11.1 mM, PG2 less than 7.8 mM), 4) IGT by WHO, nondiagnostic by NDDG (FPG less than 7.8 mM, PG1 less than 11.1 mM, PG2 7.8-11.0 mM), and 5) IGT by WHO and NDDG (FPG less than 7.8 mM, PG1 greater than or equal to 11.1 mM, PG2 7.8-11.0 mM). Established markers of abnormal glucose tolerance were also measured, including glycosylated hemoglobulin A1, insulin response, plasma triglycerides, serum uric acid, and rate of hypertension in Israel as well as rates of hypertension, peripheral vascular involvement, family history of diabetes, and history of cholelithiasis in the U.S. Accounting for potential confounders, levels of these markers in both national samples were similar in categories 1 and 2 and in categories 3-5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583382 TI - [The effect of simultaneous performance of static and dynamic loads on changes in routine physical work capacity]. PMID- 2583383 TI - [The relation of infralow-frequency fluctuations of external electrical fields to electrophysical parameters of the body]. PMID- 2583384 TI - [The "final" potential in muscle forces of various durations]. PMID- 2583385 TI - [Neurologic informatics: its bases, current status and outlook]. PMID- 2583386 TI - [The action of dilantin on the state of consciousness]. PMID- 2583387 TI - [The dependence of physical work capacity on genotype in unpleasant weather]. PMID- 2583388 TI - [The significance of the design of a dichotic test in research on functional asymmetry of the brain]. PMID- 2583389 TI - [Rapid eye movements during sleep]. PMID- 2583390 TI - [The influence of the level of neuroticism on the development of adaptation]. PMID- 2583391 TI - [A method for the objective assessment of human capacity to sense the bitter taste of phenylthiocarbamide]. PMID- 2583393 TI - [Pain sensitivity indices of stenocardia patients and healthy subjects]. PMID- 2583392 TI - [A multichannel cortical electrode for recording the neuronal impulse activity of the human cerebral cortex]. PMID- 2583394 TI - [Characteristics of the transitional process of heart rhythm during an active orthostatic test in middle-aged and elderly subjects]. PMID- 2583395 TI - [Resonance phenomena in the EEG during photostimulation with a changing burst frequency. 2. Regional characteristics of the resonance effects]. PMID- 2583396 TI - [The normal index of attention and short-term memory and in neuroses in youth]. PMID- 2583397 TI - [The autonomic indices of children and adolescents under emotional stress]. PMID- 2583399 TI - [Age-related changes in the ventilation function of the lungs and in the hemodynamics of the lesser circulation in children and adolescents]. PMID- 2583398 TI - [Indices of respiration and the cardiovascular system during the bicycle ergometry test in boys 10-11 years of age]. PMID- 2583400 TI - [Age-related changes in hemodynamics at rest and under physical loading in relation to the functional status of young athletes]. PMID- 2583401 TI - [The regulation of glucocorticoid secretion during sports activity]. PMID- 2583402 TI - [Age-related characteristics of the ion-regulating function of the kidneys]. PMID- 2583404 TI - [An integral index of visual information processing]. PMID- 2583406 TI - Effect of exercise and physical fitness on large intestinal function. AB - The effect of exercise on large intestinal function has been determined in 14 healthy but normally sedentary men and women, aged 22-34 yr while on a constant diet. For an initial 3-5-wk period (control) no activity was allowed. Six subjects then undertook a 9-wk training schedule by the end of which they were capable of jogging for 1 h per day, 5 days a week. A further 6 subjects undertook a similar training schedule that lasted for only 7 wk, at the end of which they were jogging for 45 min per day. Finally, 2 subjects were studied continuously while taking light exercise for 6 wk and then jogging for a further 3 wk. Physical fitness was monitored and showed significant changes with maximum aerobic capacity increasing from 2.4 +/- 0.5 to 3.1 +/- 0.4 L/min, maximum heart rate after a step test falling from 152 +/- 8 to 129 +/- 5 beats per minute, and resting pulse rate also falling from 56 +/- 4 to 50 +/- 5 beats per minute. High density lipoprotein cholesterol also increased significantly. Colonic function was assessed by measurement of stool weight and transit time, using the continuous radiopaque marker technique, fecal pH, nitrogen excretion, and ammonia concentration. No change was observed overall in mean daily fecal weight [124 +/- 39 (control) and 129 +/- 49 g/day (exercise)], transit time [55 +/- 20 (control), 54 +/- 23 h (exercise)], nor in fecal frequency, dry stool weight, pH, ammonia, or total nitrogen excretion. Significant changes did occur in 5 individuals with significant slowing of transit time in 2 and speeding up in 3. Overall transit time increased in 9 subjects and decreased in 5; hence, when diet is constant, exercise has marked effects on physical fitness but no consistent effect on large bowel function. PMID- 2583405 TI - Reorganizing the AGA: why, how, and when. PMID- 2583403 TI - [Psychological status and metabolic function under the action of high temperature and humidity]. PMID- 2583407 TI - Regulation of eicosanoid production in rabbit colon by interleukin-1. AB - Prostaglandins and thromboxanes are increased in human and experimental colitis, but the factors that regulate this enhanced production are unclear. The present studies evaluate the effects of the monokines, interleukin-1 alpha and beta on eicosanoid production in rabbit colon. In tissue incubations the peak dose response of eicosanoid release to human recombinant interleukin-1 is 50 ng/ml. Interleukin-1 alpha increases prostaglandin E2 (PGE2) by 4.5 +/- 1.9 ng/g tissue, 6-keto PGF1 alpha by 6.2 +/- 2.7 ng/g, and thromboxane B2 by 2.1 +/- 0.3 ng/g compared to placebo. In isolated rabbit colons perfused with Krebs' solution, 10 h infusion of interleukin-1 alpha (50 ng/ml) progressively increases production of PGE2, 6-keto PGF1 alpha, and thromboxane B2. Bolus injections of bradykinin increase production of PGE2, but not 6-keto PGF1 alpha and thromboxane B2, and these responses are markedly augmented by interleukin-1 alpha: at 10 h bradykinin stimulated PGE2 production is 518 +/- 104 vs. 95 +/- 18 ng/5 min (p less than 0.005), 6-keto PGF1 alpha is 172 +/- 88 vs. 8 +/- 2 ng/5 min (p less than 0.02), and thromboxane B2 is 60 +/- 14 vs. 13 +/- 4 ng/5 min (p less than 0.02) for interleukin-treated colons vs. placebo-treated colons, respectively. The response is greater with interleukin-1 alpha than interleukin-1 beta. This study demonstrates that interleukin-1 stimulates prostaglandin and thromboxane production in normal colon tissue. These data are consistent with the concept that interleukin-1 production by inflammatory cells may augment prostaglandin and thromboxane production in colitis. PMID- 2583408 TI - Gastrin is a major mediator of the gastric phase of acid secretion in dogs: proof by monoclonal antibody neutralization. AB - We developed a monoclonal antibody, 28.2, that binds specifically to the amidated carboxyl terminal region common to gastrin and cholecystokinin. This immunoglobulin G1 antibody has high affinity (ID50 = 30-70 pM for gastrin and cholecystokinin peptides), binds labeled gastrin similarly at 37 degrees C and 4 degrees C, and shows minimal inhibition of binding in the presence of 40% canine serum. Antibody 28.2 was used to carry out in vivo immunoneutralization studies in 8 dogs previously prepared with chronic gastric fistulas. Preliminary studies revealed that a single intravenous dose of 0.75 mg of partially purified immunoglobulin G of monoclonal antibody 28.2 completely inhibited the acid stimulatory effect of exogenous gastrin-17 given intravenously at 200 pmol/kg.h, a physiologic dose, and inhibited by 70% the acid response to a supraphysiologic dose, 800 pmol/kg.h. The same dose of antibody decreased the acid secretory response obtained during distention of the stomach with 300 ml of 5.8% glucose solution by 98% and decreased the response to distention with 300 ml of 8% peptone solution by 68%. A 10-fold higher dose of antibody decreased the acid response to peptone by 96%. The gastrin antibody had no effect on the acid response to exogenous histamine. A control antibody, specific for the biologically inactive glycine-extended gastrin/cholecystokinin peptapeptide region, had no significant effect on gastric acid secretion stimulated by gastrin or by gastric distention with nutrients. These studies indicate that circulating gastrin is of major importance in the gastric phase of gastric acid stimulation caused by distention of the stomach with nutrients. PMID- 2583409 TI - Activation of the complement system in primary sclerosing cholangitis. AB - Recent evidence, including the presence of circulating immune complexes, suggests that abnormalities of humoral immunity may be important in the pathogenesis of primary sclerosing cholangitis. The aim of the present study was to determine whether activation of the complement system is present in patients with this disease, as this would be supportive evidence of a role for circulating immune complexes in primary sclerosing cholangitis. Plasma complement fragments C3d and C4d, and serum C3 and C4, their respective parent molecules, have been assayed. Both C3d and C4d were elevated in patients with primary sclerosing cholangitis compared with patients with extrahepatic obstructive cholestasis and normal controls (p less than 0.01 in all instances). C3 was elevated in both patient groups, in whom it was similar, compared with normal controls (p less than 0.001 in both cases), whereas C4 was similar in all groups. Elevated levels of circulating immune complexes were identified in 21 of 24 (88%) patients with primary sclerosing cholangitis, but in none of the normal controls. These findings support the hypothesis that in primary sclerosing cholangitis circulating immune complexes are associated with activation of complement via the classical pathway. PMID- 2583410 TI - Lack of association between oral contraceptive use and Crohn's disease: a community-based matched case-control study. AB - Previous epidemiologic studies have suggested a weak association between oral contraceptive use and Crohn's disease, specifically Crohn's colitis. To measure a possible etiologic association, 51 women with Crohn's disease who were 18-50 yr old were studied and compared with peer-nominated age- and sex-matched controls. There were no differences between cases and controls with respect to race, religion, marital status, and number of pregnancies. There was no association between oral contraceptive use and Crohn's disease incidence [current use: odds ratio (OR) 0.73, 95% confidence interval (CI) 0.34-1.59; former use: OR 1.80, CI 0.61-5.29; current or former use: OR 1.00, CI 0.46-2.16]. Stratifying by disease location also failed to identify an association. Cigarette smoking was significantly associated with Crohn's disease incidence. Controlling for possible confounding effects of cigarette smoking did not alter the lack of association between oral contraceptive use and Crohn's disease. Similarly, testing for interaction failed to demonstrate any effect modification. Analyzing for duration of current oral contraceptive use or time interval since last use failed to demonstrate a "dose-response" effect. The study was of sufficient size to detect statistical significance for oral contraceptive use for odds ratios of greater than or equal to 2.76. From this community-based matched case-control study, there was no association between oral contraceptive use and Crohn's disease, and women need not be advised to discontinue oral contraceptive use when a diagnosis of Crohn's disease is made. PMID- 2583411 TI - Rapid decrease in electrical conductance of mammalian duodenal mucosa in vitro. Combined effects of prostaglandin E2 and bicarbonate. AB - The effects of HCO3- on transepithelial conductance of guinea pig (and, in some experiments, rabbit) duodenum have been investigated using stripped preparations in Ussing-type chambers. Initial conductance amounted to approximately 27 mS/cm2. In the presence of serosal or bilateral HCO3- (20 mM), it fell to approximately 15 mS/cm2 within 60 min. With mucosal HCO3- or HCO3- -free solutions, conductance decreased to only approximately 23 mS/cm2. In the absence of HCO3-, serosal but not mucosal addition of HCO3- prompted a steep conductance drop that was 50% complete within 6 min. These effects were the same in proximal and distal segments, whereas conductance levels in the latter were higher. The effects of HCO3- required serosal Na+; they were partly prevented or reversed by serosal ouabain (3 x 10(-5) M), furosemide (10(-3) M), and other loop diuretics, and indomethacin (10(-5) M). Serosal addition of prostaglandin E2 (10(-7) M, followed by 10(-6) M) reduced conductance from approximately 22 to approximately 17 mS/cm2. This effect required serosal HCO3- and the presence of indomethacin. 8-Br cyclic adenosine monophosphate (10(-3)M, serosal side) mimicked the effects of prostaglandin E2. Indomethacin and prostaglandin E2 did not influence the secretory flux of HCO3- (approximately 0.5 mumol/cm2.h, pH-stat method). Our results assign a critical role to serosal HCO3- in the maintenance of a low tissue permeability, dependent on the availability of prostaglandins (cyclic adenosine monophosphate) and involving HCO3- access to the cell rather than secretion. PMID- 2583412 TI - Long-term influence of enteric infection on jejunal propulsion in guinea pigs. AB - The intrinsic fluid-propelling behavior of guinea pig jejunal segments was reportedly altered by primary infection with Trichinella spiralis from day 10 to day 20 postinoculation. After that time propulsive behavior returned to normal. The objective in the investigation reported here was to determine if jejunal responsiveness to an infection is influenced by prior exposure to the parasite. Accordingly, jejunal propulsion was examined in guinea pigs reinfected 2 mo after the initial inoculation with the parasite. Propulsive behavior was measured in vitro by attaching oral and aboral ends of jejunal segments to a propulsion evaluation system that imposed input-output conditions of constant capacitance and negligible resistance. Propulsive complexes produced by segments removed from animals 60 days after primary inoculation were generally similar in configuration to those produced by segments from uninfected hosts. The pronounced net aboral propulsive behavior previously observed 10-20 days after primary infection was not observed in segments from animals 60 days postinfection or from uninfected controls. After secondary inoculation the fluid volume expelled per propulsive complex began to increase within 1 day and net aboral propulsive behavior was clearly evident 2 days postinoculation. As net aboral propulsive behavior was induced approximately five times faster after secondary as compared with primary inoculation with T. spiralis, it is evident that the overall intrinsic mechanisms that are responsible for an earlier onset of net aboral propulsive behavior are responsive for at least 2 mo after initial exposure to the parasite. PMID- 2583413 TI - Upper esophageal sphincter opening and modulation during swallowing. AB - Studies were done on 8 normal subjects with synchronized videofluoroscopy and manometry to facilitate a biomechanical analysis of upper esophageal sphincter opening and volume-dependent modulation during swallowing. Movements of the hyoid and larynx, dimensions of sphincter opening, and intraluminal sphincter pressure were determined at 1/30th-s intervals during swallows of 1, 5, 10, and 20 ml of liquid barium. Our analysis subdivided upper esophageal sphincter activity during swallowing into five phases: (a) relaxation, (b) opening, (c) distention, (d) collapse, and (e) closure. Sphincter relaxation occurred during laryngeal elevation and preceded opening by a mean period of 0.1 s. Opening occurred as the sphincter was pulled apart via muscular attachments to the hyoid such that the hyoid coordinates at which sphincter opening and closing occurred were constant among bolus volumes. Sphincter distention after opening was modulated by intrabolus pressures rather than graded hyoid movement. The generation of intrabolus pressure coincided with the posterior thrust of the tongue that culminated in pharyngeal wall contact and the initiation of pharyngeal peristalsis. Larger volume swallows were associated with greater intrabolus pressure and increased bolus head velocity. The duration of sphincter opening increased in conjunction with a prolongation of the anterior-superior excursion of the hyoid and a delay in the onset of pharyngeal peristalsis (the event that determined the timing of sphincter closure). We conclude that transsphincteric transport of increasing swallow bolus volumes is accomplished by modulating sphincter diameter, opening interval, and flow rate (reflected by bolus head velocity). Furthermore, upper esophageal sphincter opening is an active mechanical event rather than simply a consequence of cricopharyngeal relaxation. PMID- 2583414 TI - Gallbladder contraction in patients with pigment and cholesterol stones. AB - Thirty gallbladders were studied in vitro; 5 had black pigment stones and 25 contained manifestations of excess cholesterol in bile. Of the 25, 14 had cholesterol stones, 7 had macroscopic cholesterolosis, and 4 had cholesterol crystals. There were no differences in basal active tension among these groups, but the force of spontaneous phasic contractions was reduced in gallbladders with cholesterol stones, cholesterolosis, and cholesterol crystals compared with specimens with pigment stones (p less than 0.001). The forces developed in response to cholecystokinin-8 (10(-10)-10(-6) M), acetylcholine (10(-7)-10(-3) M), and potassium chloride (20-60 mM) were greater in strips from specimens with pigment stones than in strips from specimens with cholesterol stones or cholesterolosis (p less than 0.001). In cholesterol stones and cholesterolosis specimens, relatively strong muscle strips had similar responses to 10(-6) M cholecystokinin-8 in normal calcium (2.5 mM) and in the absence of extracellular calcium. Weaker muscle strips had a reduced response to cholecystokinin-8 in the absence of extracellular calcium (p less than 0.01). It is concluded that muscle strips exposed to bile with excess cholesterol have a reduced contractility compared with muscle strips from specimens with pigment stones; this impaired contractility precedes gallstone formation, and results from muscle dysfunction. PMID- 2583415 TI - Bile acid synthesis in humans: regulation of hepatic microsomal cholesterol 7 alpha-hydroxylase activity. AB - The present work tested the hypothesis that portal venous bile acids regulate the activity of the cholesterol 7 alpha-hydroxylase and studied the influence of hepatic microsomal free cholesterol concentration on the enzyme activity. Operative liver biopsies and samples of portal venous blood were obtained from a total of 61 patients with gallstones who were undergoing cholecystectomy. Fifteen of the patients were treated with cholestyramine (16 g/day) for 2-3 wk before operation and 23 patients with chenodeoxycholic acid (15 mg/kg.day) or ursodeoxycholic acid (15 mg/kg.day) for 3-4 wk before operation. Highly accurate methods based on isotope dilution-mass spectrometry were used for assay of the cholesterol 7 alpha-hydroxylase activity, the concentration of free cholesterol in the microsomes, and the levels of individual bile acids in portal venous blood. Cholestyramine treatment increased the cholesterol 7 alpha-hydroxylase activity about sixfold, from 7.6 +/- 1.1 (mean +/- SEM) to 45.7 +/- 6.7 pmol/min.mg protein. Administration of chenodeoxycholic acid reduced the enzyme activity considerably to 1.0 +/- 0.3 pmol/min.mg protein, whereas ursodeoxycholic acid did not significantly affect the enzyme activity (7.9 +/- 2.2 pmol/min.mg protein). The concentration of microsomal free cholesterol remained essentially unchanged in spite of a 45-fold variation in enzyme activity. There was a negative correlation between the absolute as well as the relative concentration of chenodeoxycholic acid in portal blood and the activity of the cholesterol 7 alpha-hydroxylase, whereas there was no correlation between the total concentration of bile acids and the enzyme activity. It is concluded that the composition of individual bile acids may be more important than the total concentration of bile acids in the portal vein for the regulation of the cholesterol 7 alpha-hydroxylase activity in humans. It is further concluded that chenodeoxycholic acid is a considerably stronger suppressor of bile acid synthesis than ursodeoxycholic acid. PMID- 2583417 TI - Dietary intake and the prevalence of gallbladder disease in Mexican Americans. AB - Mexican Americans have a high prevalence of gallbladder disease. We examined the contribution of ethnic preferences in food intake to the risk of gallbladder disease in Mexican Americans and non-Hispanic whites. Participants in a population-based health survey were questioned about any history of gallbladder disease, and were interviewed to determine their dietary intake. After adjusting for age, body mass index, and ethnic group, we found that women with the highest intake of total fat and linoleic acid had reduced risks of gallbladder disease, although an opposite trend was observed in men. High levels of sucrose intake and low levels of cholesterol intake were associated with an increased risk for both sexes, but the odds ratios were not statistically significant. Although Mexican Americans and non-Hispanics differed in their intake of several nutrients, the elevated risk of gallbladder disease in Mexican American women was unchanged after ethnic differences in food intake were taken into account. Although the dietary preferences of Mexican Americans as reflected in 24-h diet recall interviews do not appear to explain their high prevalence of gallbladder disease, this finding should be interpreted with caution because of methodologic limitations in measuring habitual food intake. PMID- 2583416 TI - Reduced central blood volume in cirrhosis. AB - The pathogenesis of ascites formation in cirrhosis is uncertain. It is still under debate whether the effective blood volume is reduced (underfilling theory) or whether the intravascular compartment is expanded (overflow theory). This problem has not yet been solved because of insufficient tools for measuring the central blood volume. We have developed a method that enables us to determine directly the central blood volume, i.e., the blood volume in the heart cavities, lungs, and central arterial tree. In 60 patients with cirrhosis and 16 control subjects the central blood volume was assessed according to the kinetic theory as the product of cardiac output and mean transit time of the central vascular bed. Central blood volume was significantly smaller in patients with cirrhosis than in controls (mean 21 vs. 27 ml/kg estimated ideal body weight, p less than 0.001; 25% vs. 33% of the total blood volume, p less than 0.0001). The lowest values (18 ml/kg) were found in patients with gross ascites and a reduced systemic vascular resistance. In patients with cirrhosis central blood volume was inversely correlated to the hepatic venous pressure gradient (r = -0.41, p less than 0.01), and the total blood volume was inversely correlated to the systemic vascular resistance (r = -0.49, p less than 0.001), the latter being significantly reduced in the patient group. Patients with cirrhosis apparently are unable to maintain a normal central blood volume. This may be due to arteriolar vasodilation, portosystemic collateral flow, or sequestration of fluid in the peritoneal cavity, or any combination thereof. The present results indicate that central circulatory underfilling is an integral part of the hemodynamic and homeostatic derangement observed in cirrhosis. PMID- 2583418 TI - Pancreatobiliary responses to an intragastric amino acid meal: comparison to albumin, dextrose, and a maximal cholecystokinin stimulus. AB - Little is known about how gastric and pancreatobiliary responses differ after intake of elemental diets from responses to polymeric food. We therefore compared pancreatic and biliary secretions after gastric instillation of albumin (7 g%, with dextrose 21 g%) with an elemental diet in 6 healthy volunteers. The elemental diet contained amino acids (7 g%, with dextrose 21 g%) in the same molar composition as the albumin. Furthermore, we studied the effect of a pure intragastric dextrose solution (21 g%) on pancreatobiliary secretions, as glucose constitutes a major component of elemental diet formulas. The various pancreatobiliary responses were tested against a maximal i.v. cholecystokinin stimulus. The dextrose, amino acid, and albumin meals emptied at similar rates, and gastric emptying was completed within 3 h. Similar pancreatobiliary responses were observed after the albumin and amino acid meals, but response to both the amino acid and albumin meals was smaller than to the intravenous cholecystokinin stimulus. The glucose meal caused a marked and sustained stimulation of pancreatobiliary outputs, which did not differ significantly from the other test meals. However, lower cholecystokinin levels were observed after the glucose meal compared with distinct cholecystokinin release after the albumin and amino acid meals. We conclude first that there are no major differences in secretory responses between elemental (amino acid) and polymeric (protein) meals and second, that intragastric pure glucose meals strongly stimulate pancreatobiliary secretions. The marked pancreatic and biliary responses to intragastric dextrose cannot be fully explained on the basis of cholecystokinin release, suggesting that this response is probably mediated by neural mechanisms. PMID- 2583419 TI - Collagenous gastritis. AB - Subepithelial fibrosis has previously been reported in the small intestine (collagenous sprue) and colon (collagenous colitis). We report a 15-yr-old girl with chronic gastritis and subepithelial fibrosis of the gastric corpus who presented with recurrent abdominal pain and acute upper gastrointestinal bleeding. Nodularity and erythema of the gastric corpus were persistent endoscopic findings. Biopsies revealed patchy chronic active gastritis with a striking focal thick band of collagen immediately beneath the surface epithelial cells that did not extend to deeper portions of the lamina propria. Contrast radiography demonstrated an abnormal mucosa of the gastric corpus with a mosaiclike surface pattern. Numerous studies have failed to elucidate the etiology. Despite treatment with ranitidine, sucralfate, and furazolidone, there has been no clinical or pathologic improvement. The pathogenesis and prognosis of collagenous gastritis, and its relationship to collagenous sprue and collagenous colitis, remain to be defined. PMID- 2583420 TI - Animal research and the practicing gastroenterologist. PMID- 2583422 TI - Detection of colorectal liver metastases: which imaging technique is best? PMID- 2583421 TI - Transforming growth factors and intestinal epithelia: more questions than answers. PMID- 2583423 TI - Endoscopy for gallstone pancreatitis. PMID- 2583424 TI - Effect of cholecystectomy on bile acid kinetics. PMID- 2583425 TI - Protein kinase C subspecies. PMID- 2583427 TI - [Functional forms of prolapse]. AB - 234 women were examined via microtransducers both with 100 ml bladder contents in recumbent position and with 300 ml bladder contents in seated position. The types of prolapse or descensus were categorised after modification according to Green. The quotient from the maximal urethral occlusion pressure at rest recorded with 300 ml bladder filling in seated position and 100 ml bladder filling in recumbent position (known as pressure quotient at rest) showed changes dependent on the type of prolapse (Type I: less than or equal to 1, Type II: less than 1, Type III: greater than 1 (n.s.), Type IV: greater than 1). These functional changes can be explained by the stress-dependent dynamics of each individual form of prolapse. An additional combined form was described (Type III) which was found to be a special form both anatomically and functionally. PMID- 2583426 TI - Effect of FOY-305 (Camostate) on severe acute pancreatitis in two experimental animal models. PMID- 2583428 TI - [Definition and etiologic factors of hypotonic urethra in relation to urinary stress incontinence in the female]. AB - In 555 stress-induced urinary incontinent and 119 continent women patients, we studied the history, clinical and urodynamic investigations to define the hypotonic urethra and to find out important etiological factors of the low urethral closure pressure. The linear depression of the urethral pressure and the urethral closure pressure at rest--well known from literature--has been confirmed in this study. With hypotonic urethra, closure pressure values were found to be below the simple standard deviation from a norm-curve. Also, in cases of stress urinary incontinence, we found a nearly linear depression of closure pressure. The stress incontinent patients could be divided in two groups: 46% with hypotonic urethra, 54% with nearly normal closure pressure. History of former incontinence surgery, but also of other operations such as simple abdominal or vaginal hysterectomy, is correlated with low urethral closure pressure. The degree of closure pressure is correlated with shortening of the functional urethral length. The maximum closure pressure shifts distally. Women, who, despite hypotonic urethras, are continent, build up a positive closure pressure throughout a broad zone of the functional urethral length. Contrarily, in the case of incontinent patients, even a weak coughing spasm, which does not even break through the bladder sphincter in maximum closure, can cause opening of the urethra and establishment of pressure equilibration between bladder and urethra. PMID- 2583429 TI - [Recurrence rate following surgery of incontinence in patients with hypotonic urethra]. AB - In a retrospective study, 94 patients were examined after incontinence operation. We show the anamnestic, clinical and urodynamic results. Standardised questions were used for exploring the patients' history. The loss of urine during provocation, like coughing with a filled bladder up to 300 ml, showed the clinical incontinence. The urodynamic investigations were performed with a modern, computer-guided instrument. The pressure was measured by highly flexible polyurethane catheters with micro-tip pressure transducers. The examinations were made in horizontal position with 100 ml, and upright position with either 100 ml or 300 ml bladder volume. Approx. 50% of the examined patients had postoperative stress incontinence both anamnestically and urodynamically. After vaginal repair and the Marshall-Marchetti-Krantz procedure, regardless of maximal urethral closure pressure (UVDR max), the recurrence rate was doubled in comparison to Burch colposuspension. After dividing all patients into those with hypotonic and those with normotonic urethra, the recurrence rate was doubled when UVDR max was low. The comparison of vaginal repair and abdominal colposuspension in patients with hypotonic urethra showed a significantly higher recurrence rate in the first group. In a preliminary prospective study, 19 patients with hypotonic urethra prior to surgery underwent Burch colposuspension. The examinations 3-6 months later did not show any stress incontinence. The main UVDR max ascended from 28.2 to 38.2 cm H2O. The increase was statistically significant (p less than 0.003). Unsatisfactory results after incontinence operations were obtained on patients with vaginal repair with hypotonic urethra. Preliminary results show, that after Burch colposuspension on patients with low maximal urethra closure pressure, a reduction of recurrence may be achieved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583430 TI - [Comparison of various length parameters of the urethra in 386 patients in relation to continence, menopausal status and age]. AB - 368 urodynamically investigated women of the University Hospital of Innsbruck (Austria) were separated into four groups depending on their incontinence status (either stress incontinence or not) and depending on previous incontinence surgery. In this collective of patients, we compared the urethral length, the absolute and relative functional urethral length and the absolute and relative length from the bladder to the point of maximum urethral closure pressure with the patients' age and menopausal status. The analysis showed a dependence of the urethral length on age and menopausal status in women having undergone no previous incontinence surgery, who suffered from genuine stress incontinence. In these patients, the relative length from the bladder to the point of maximum urethral closure pressure also depended on the menopausal status. In women with no previous surgical treatment showing no symptoms of genuine stress incontinence, we could find a relationship between the age of the patients and the relative length to the point of maximum urethral pressure. Furthermore we could show that, in continent patients, the distance bladder - point of maximum urethral closure pressure was more often longer than 60% of the functional urethral length than in patients suffering from genuine stress incontinence. PMID- 2583431 TI - [Initial experiences with hysterosalpingoscintigraphy in normal and pathologic fallopian tube passage]. AB - A prospective study in 38 patients was designed to evaluate the efficacy and reliability of radionuclide hysterosalpingoscintigraphy (HSS) using 99mTc labelled human albumin macroaggregates (HAMA). Following application in the posterior vaginal fornix at the time of ovulation, HAMA normally migrate spontaneously through the uterus and tubes and may be identified after 20 min (range 5-90 min) in the uterine cavity and after 2 hrs (range 40 min - 3 hrs) in the free pelvis, using a gamma camera. When correlated with the findings of conventional contrast hysterosalpingography (HSG), the radionuclide procedure yielded comparable results in females with patent or clearly obstructed tubes. Using 8-10 MBq 99mTc, radiation exposure was estimated to be 0.75 cGy per ovary, which is considerably less than the mean dose absorbed with HSG. As the HSS procedure imitates the migration of spermatozoa by the means of an inert tracer, it allows a direct insight in the mechanisms of passive transport taking place in the uterus and tubes at the period of ovulation. Thus, it reflects the physiological state of the female reproductive tract. On the basis of the scintigraphic findings, equivocal results on HSG have to be re-evaluated, as tubes, which are anatomically patent under high pressure, may be functionally deficient. PMID- 2583432 TI - [Intra-tubal embryo transfer (IVF/IT-ET) in the treatment of non-tubal-induced sterility. Initial studies of the value of a new and expensive therapy procedure]. AB - Intratubar embryo transfer is a form of sterility treatment, in which the in vitro-fertilized pre-implantation embryos are transferred into the intact fallopian tube(s). This enables the benefits of in-vitro fertilization (information of the gamete fertilization behavior, specific incubation of dysmature oocytes, reduction of the polyploidy rate, risk of multiple pregnancies) to be combined with those of gamete intrafallopian transfer (GIFT; tubar environment for the further development of the pre-implantation embryos). Intratubar embryo transfer is indicated in cases of sterility that are not due to the fallopian tubes; in addition to idiopathic sterility, particular emphasis is put on a certain form of immunological sterility (antibodies against sperm antigens), which seems to be a special indication for this method. Intratubar embryo transfer demands a two sided approach. It is advisable to collect the oocytes transvaginally, guided by ultrasound, since general anaesthesia maybe dispensed with - if so desired. The embryo transfer itself still requires a pelviscopy, which is only performed once fertilization of the oocyte has been confirmed; which is in contrast to GIFT, in which pelviscopy is an inherent part of each treatment cycle. In spite of this advantage, intratubar embryo transfer is a method, which is associated with a high expenditure. The aim of the study was, to evaluate the success rate when all the alternative, less costly options have been exhausted. Our first results are demonstrating, that intratubar embryo transfer is successful, even as a second line therapy. Therefore the method has a significance in the treatment of sterility, not caused by the tubes and the expenditure, with which it is associated, can be justified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583434 TI - [Comment on the contribution by E. Kuss. On adding tests for anti-HIV-IgG to the general prenatal examination of pregnant patients]. PMID- 2583433 TI - [Pregnancy-induced gigantomastia]. AB - Gigantomastia complicating pregnancy is rare and of unknown etiology. Medical treatment does not lead to a lasting improvement. We favour surgical treatment, involving plastic reconstructive aspects. PMID- 2583435 TI - [Interferon in the treatment of condylomata acuminata]. AB - In the present study we used the well known antiviral properties of interferon alpha 2b in condylomata acuminata. Firstly we investigated 3 different application forms. We found that 1. the local INF application in gel was completely ineffective, 2. the injection of INF into the base of the warts was effective but too painful for routine therapy, 3. the systemic treatment by s.c. injection had an excellent compliance and a high efficacy. In the second part of the study we treated 16 patients with our own s.c.-regimen of 3 x 5 mill. U and 6 x 2 mill. U INF alpha 2b within 5 weeks. 60% showed a complete response, 30% a partial response; these were treated surgical afterwards. In none of the patients a relapse occurred at a median follow-up of 11 months. The observed side-effects were poor. We consider the systemic treatment with interferon for condylomata acuminata to be highly effective and well tolerated. The relapse rate is very poor. PMID- 2583436 TI - [The "HELLP syndrome" without fragmentocytes: do drug-induced antibodies play a role?]. AB - This is a case report on a nulliparous women, who developed the HELLP syndrome following intravenous tocolysis. Contrary to our expectations, neither schistocytes nor signs of intravasal coagulation were apparent; however, we found Fenoterol-associated anti-erythrocyte antibodies. However, the low titre of these antibodies does not explain the massive haemolysis. It is suggested, that these antibodies represent a causal factor in developing the HELLP syndrome. PMID- 2583437 TI - [Clostridium infection in the puerperium following cesarean section]. AB - Clostridium perfringens infections in the puerperal period are rare. A 22-year old patient, after caesarean section at another hospital, was admitted to our clinic showing clinical signs of haemolysis, slight uraemia, a crepitation of tissue and sonographical signs of air bubble formation in the uterus. Since clostridium perfringens infections show a high mortality rate, early operative measures under high-dose Penicillin treatment are indicated. In this case, hysterectomy and salpingectomy were performed. Both ovaries were unaffected and could be conserved. In addition, a peritoneal lavage was done. Our patient was discharged as cured after a postoperative course without any complications. There is no evidence in the literature for the efficacy of either antitoxin treatment or a high oxygen therapy. PMID- 2583439 TI - [Extrauterine pregnancy following abruptio placentae with lacking proof of intrauterine pregnancies]. PMID- 2583438 TI - [Metastasizing malignant melanoma of the vagina]. AB - We report on a 54-year-old patient with multiple cutaneous, lung and liver metastases. The primary tumour is a malignant melanoma of the vagina, who developed within one year after the last gynaecological examination. Our case report is another example for the poor prognosis of this rare vaginal tumour. PMID- 2583441 TI - [The normal fetal intestinal tract in correlation to gestational age. An amniofetography study]. AB - Amniofetography represents an adequate method to study prenatally the fetal gastrointestinal tract in utero. In 108 pregnancies without fetal intestinal anomalies, the course of intestinal growth with regard to the lumen of certain parts of intestine has been analyzed. The results agree with those of other authors using sonography to study the intrauterine development of fetal intestinal tract. The demonstrated kinetics of contrast media passage through the gastrointestinal tract, following its intra-amnion application, contribute the knowledge of normal fetal physiology. PMID- 2583440 TI - [Plastic surgery correction of combination craniofacial malformations. A survey for the obstetrician]. AB - Complex malformations of the skeleton of the cranium and face are mostly first discovered by the obstetrician. Almost all anomalies can be corrected already at infant age by means of update craniofacial surgery, provided they are diagnosed well in time and treatment is initiated directly. Surgery should be performed by a team that is well-versed in craniofacial surgery. A few examples are given to illustrate the most important malformations. Pointers to the best possible time of operation, indication and method are supplied. PMID- 2583442 TI - [Maternal and neonatal bupivacaine plasma levels in peridural anesthesia for relief of labor pain]. AB - Peripheral venous blood samples were drawn for bupivacaine analyses (gas chromatography) from 24 patients under epidural anaesthesia, used to reduce pain caused by contractions. The specimens were taken 10, 20, 30 and up to 45 minutes following a first injection of 11 to 13 ml bupivacaine 0.25%, before, 15 as well as 30 minutes after each repetitive dose and at childbirth. Immediately after cord clamping, blood sampling in the neonate was performed to evaluate bupivacaine concentrations in the umbilical artery and vein. Additionally, apgar scores and blood gas parameters were checked and compared with those of neonates, born without analgesic treatment of their mothers. Using bupivacaine 0.25% (average 12 ml) for epidural anaesthesia, the peak plasma levels (mean = 0.2 micrograms/ml) were found 10 minutes after application of the analgesic dose. In one patient a maximum bupivacaine plasma concentration (0.47 micrograms/ml) was determined 15 minutes after the second repetitive dose of 5 ml bupivacaine 0.25%. Apgar scores and results of blood gas analyses demonstrated no significant difference between neonates born spontaneously under regional anaesthesia or without any analgesic treatment of their mothers, respectively. Using bupivacaine 0.25% in epidural anaesthesia for pain relief in labour, we found maternal and neonatal plasma concentrations of the local anaesthetic drug far below the accepted threshold level which might produce systemic toxic reactions. PMID- 2583443 TI - [Senna-containing laxatives: excretion in the breast milk?]. AB - The excretion of rhein, a cathartic with active metabolite from sennosides, was investigated in breast milk samples of 15 post-partum women for at least 24 h after the intake of a therapeutic dose (15 mg sennosides/day) of a standardized, fiber containing senna laxative (Agiolax). Rhein was analyzed by a HPLC-method with a lower limit of detection at 1 ng/ml rhein, taking into account a possible binding as monoglucuronide and monosulfate. Maximal concentrations up to 27 ng/ml and in 89% values below 10 ng/ml were measured. Related to the daily milk volume, 73% of the women excreted less than 2 ng rhein/day. Based on median values, 0.017% of the sennoside intake (calculated as rhein) was excreted in breast milk. The amount of rhein transmitted to the infant is therefore 0.3% of the rhein intake of the mother. This is far below the oral rhein dose necessary for inducing a laxative effect. Accordingly, none of the breast-fed infants (n = 8) showed any difference in stool consistency in comparison with the non breast-fed infants. PMID- 2583444 TI - [Diagnostic in-vitro fertilization]. AB - Unexplained sterility is one of the major problems in the treatment of childless couples. The reason for sterility can be the result of different factors such as andrological or anatomic-physiological dysfunctions. The therapeutic approach to treat patients with unexplained sterility at the Department of Obstetrics and Gynecology, University of Goettingen, is, to exclude those patients from further therapies who obviously have no chance to become pregnant by any technique of reproductive medicine. A so called "diagnostical IVF" gives information about the fertilization capacity of male and female gametes in vitro. The results of a one year study with 85 couples (tubal sterility = 57; idiopathic sterility = 28) indicated, that even with no differences in the number of oocytes retrieved, the fertilization and cleavage rates were significantly higher in the group of patients with tubal sterility (fertilization rate: 63.1% vs 46.1%; cleavage rate: 57.5% vs 40.6%). Thus the transfer rate in patients with unexplained sterility was about 15% lower (68.9%) than in patients with tubal sterility (85.6%). On the other hand, after embryo transfer the pregnancy rate was double in those patients with unexplained sterility (38.7 vs 15.7%). If there is no fertilization of the oocytes in at least two IVF cycles all attempts to fulfill the patients desire for a child seem useless. In contrast successful in vitro fertilization provide the bases for further intrauterine insemination cycles which can be assisted by psychotherapy. This regimen seems helpful to classify patients with unexplained sterility and avoids long lasting frustrating therapies. PMID- 2583445 TI - [The segmented phantom insert for the formation of a neovagina according to Vecchietti]. AB - Formation of a neovagina by surgical cavitation with an olive-shaped plastic form following Vecchietti, yields good functional and cosmetic results. By replacing the olive with a motile model consisting of a variable number of single segments, complications can be reduced. The newly developed model leads to better dilatation and stabilization of the newly-formed vagina. Wound secretion is drained by an interior canal and by lateral perforations. Through this canal, catheter irrigations and drug application are possible. 15 cases of this novel surgical technique are reported. PMID- 2583446 TI - [Adenomatous hyperplasia--hysterectomy or drug therapy?]. AB - Adenomatous hyperplasia of the endometrium requires either gestagen treatment or hysterectomy, depending on the patient's age and grade of hyperplasia. 51 patients, in whom adenomatous hyperplasia of grade I-III had been ascertained by curettage, were hysterectomized not more than 4 weeks following diagnosis at the Kiel University Clinic of Obstetrics and Gynecology during the years 1985-1989. Only few of the patients received hormone treatment. For all grades of hyperplasia, histological findings from curettage and hysterectomy were identical in only 40% of the cases. In patients older than 40 years, 54% of 13 patients with adenomatous hyperplasia grade III in the curettage specimen had already developed a well differentiated adenocarcinoma, which was detected in the extirpated uterus. In our opinion, when adenomatous hyperplasia of grade II or III is present in a curettage specimen in the age group over 40 years women, hysterectomy should be recommended. For younger women and for adenomatous hyperplasia grade I, we recommend individual therapy. PMID- 2583447 TI - [Trephine biopsy of the bone marrow in patients with hairy cell leukemia]. AB - The bone marrow histological picture was studied in 13 patients with hairy-cell leukemia (HCL) who were followed up at the Hematological Centre in the Latvian SSR. The diagnosis was made or proved in all the cases, among them in 9 patients on the basis of the proliferation type of leukemia cells in the bone marrow trephine biopsy that is characteristic of HCL. The analysis of the clinical and morphological features of the disease has permitted the authors to distinguish specific types of HCL: 1) splenic and bone-marrow variants predominantly were diagnosed clinically, 2) typical and atypical variants resembling malignant lymphoma or chronic lymphoid leukemia were diagnosed histomorphologically. The authors have recommended trephine biopsy+ for a wider use (as a more informative method as compared to sternal punction) in the diagnosis and differential diagnosis of HCL. PMID- 2583448 TI - [Clinico-roentgenological characteristics of acute leukemia]. AB - Combined clinico-roentgenological investigations of the thoracic organs, spleen, bone and lymphatic systems (using low lymphography) were conducted in 123 patients with acute leukemia. Clinico-roentgenological variants of acute leukemia have been distinguished, they differ in the organs and systems affected, in the process spreading by the lymphatic routes+, in the clinical course pattern and response to the treatment. Clinico-roentgenological variants of acute leukemia have shown that different pathogenetic mechanisms may act in the same cytomorphologic type of the disease. They should be taken into consideration in classification of acute leukemia. PMID- 2583449 TI - [The role of endogenous enkephalins in the regulation of bone marrow hematopoiesis in stress]. AB - A study was made of the effect of the enkephalinase inhibitor D-phenylalanine on hematopoiesis during the immobilization stress. The long-term treatment with D phenylalanine before the immobilization stress resulted in a significant increase of plasma ley-enkephalin in mice during the first day after exposure. Later the inhibition of bone marrow hyperplasia was recorded. There were no changes in hematopoiesis provided D-phenylalanine was injected after the immobilization. It is suggested that endogenous enkephalins may take part in the regulation of hematopoiesis at the early period of the stress reaction formation. PMID- 2583450 TI - [Use of the antioxidant complex of vitamins A, E and C in murine leukemia]. AB - A study was made of the content of ubiquinone, vitamins A, E, ascorbic, dehydroascorbic and diketogulonic acids (DKGA), and malonic dialdehyde (MDA) in the liver, of the content of glutathione, the activity of superoxide dismutase (SOD) and glutathione reductase in red blood cells, of the content of vitamins A, E and ubiquinone in the spleen of C57Bl/6jG mice with inoculated leukemia La. It was found that in red blood cells of the animals with leukemia, the content of vitamin E and DKGA reduced, the MDA level increased, and the content of glutathione dropped whereas SOD activity rose. Application of the antioxidant complex of vitamins A, E, C appreciably improved the characteristics of enzymatic and non-enzymatic antioxidant protection of the liver and red blood cells of the leukemic animals without exerting any noticeable effect on the content of vitamin E and ubiquinone in the leukemic spleen tissue. PMID- 2583451 TI - [Bone marrow transplantation (immunology, immunosuppression)]. AB - Clinical effectiveness of bone marrow transplantation has been analyzed in 83 patients with aplastic anemia. Bone marrow of non-related donors with high degree of histocompatibility, according to the antigen system HLA of loci A, B, C and DR, was used. Freshly prepared bone marrow was transplanted in doses from 3.4 x 10(9) to 15 x 10(9) myelokaryocytes. Immunosuppression was provided by corticosteroid hormones and antithymocytic globulin. Complete or partial remission lasting for more than a year was recorded in 56 patients. Formed elements of the donor's blood were detected in the blood of 39% of the patients (the observation period lasted from 1 to 8 months). Symptoms of a secondary disease were observed in 29% of the patients. Significant changes in the cellular immunity parameters were recorded in all the patients investigated. The character of the time course of these changes may serve as a prognostic factor of myelotherapy effectiveness. PMID- 2583452 TI - [Medico-social value of the organization and development of ambulatory hematological services]. AB - The authors have validated socio-medical and economic advantages of dispensary treatment of patients with blood diseases. It has been documented that most patients with acute leukemia can betreated on ambulatory basis. The requirement of physicians-hematologists for outpatient treatment of children and adults has been calculated. The methods of treatment suggested can be used in the public health practice. PMID- 2583453 TI - [Parameters of granulocyte proliferation in chronic myeloid leukemia and their prognostic value]. AB - A total of 112 patients with chronic myeloid leukemia were examined over time for the parameters of the proliferation of bone marrow and peripheral blood granulocytes. In the phase of blast crisis, the bone marrow demonstrated a significant rise of the portion of the G2 cells and of the mitotic index. The portion of the cells undergoing DNA synthesis in the chronic phase of the disease was not dependent on its duration. The parameters such as the mitotic index and the portion of the G2 cells in the bone marrow as well as the percentage of the cells in the S-phase in the peripheral blood correlated negatively with the patients' survival. PMID- 2583454 TI - [Evaluation of the pool of mature circulating lymphocytes in children with acute leukemia]. AB - In children with acute leukemia, at the initial period of the disease the absolute number of T-lymphocytes is within the normal range, when the values of the total number of leucocytes is low or normal, and it is increased in cases with high initial leucocytosis. Dissociation of T-cell marker signs in the lymphocyte population has been revealed that evidences the presence of functionally defective T-cells in the circulation. The value of the relative content of E+ T-cells over 10% in the circulation is of prognostic significance. PMID- 2583455 TI - [Immunodiagnosis of acute nonlymphoblastic leukemia in children]. AB - Seventy-two children with acute nonlymphoblastic leukemia (ANLL) have been studied for expression of different antigens on blast cells with the use of monoclonal antibodies. Myeloid antigens (C3bi; X-hapten) were identified on blast cells most frequently, 58.3%, Ia-like antigen was found in 55% and LFA-1 in 34% of cases. The expression of all antigens except that of LFA-1 was independent on FAB-subtype. It seems necessary in clinical practice to type ANLL cells for the expression of T-cell and myeloid antigens that are of prognostic significance. PMID- 2583456 TI - [Immunocytochemical methods using monoclonal antibodies and lectins in the diagnosis of lymphoblastic leukemia in children]. AB - ICO, IPO, LT monoclonal antibodies and lectins were used to study blood cells in 18 children with acute lymphoblastic leukemia (ALL). The immunological phenotype has been characterized, and two cytological variants of ALL of T-cell nature, and four variants of ALL of B-cell origin have been distinguished, differing by the degree of blast cell maturity. PMID- 2583457 TI - [Comparative evaluation of blast cell proliferation and effectiveness of combined chemotherapy in children with different immunocytological subvariants of acute lymphoblastic and nonlymphoblastic leukemia]. AB - It has been found that kinetic parameters of proliferation in a dominating clone of bone marrow blast cells with Ia-positive and Ia-negative phenotype, as well as with expression of myeloid differentiating antigens (ICO-GM1 and ICO-G2), or in the absence of these antigens, do not significantly differ in children with subvariants MO-M4 of acute nonlymphoblastic leukemia, sensitive and resistant to the therapy. A higher rate of the bone marrow blast cell population growth and a lower effectiveness of the combined chemotherapy have been recorded in children with T-cell and pre-B-cell acute lymphoblastic leukemia as compared to acute lymphoblastic leukemia with the phenotype of blast cells that have only Ia-like or "common" antigens. PMID- 2583458 TI - [State of nucleolus-forming regions in bone marrow and blood cells in acute leukemia in children]. AB - The study of the activity of nucleolus-forming areas in bone marrow and blood cells in 67 children with acute leukemia has shown the parameter variability depending on histogenetic affiliation, differentiation degree and on the proliferative activity of the cells. PMID- 2583459 TI - [Prospects and ways of development of child hematology]. PMID- 2583460 TI - [Results of the use of human leukocytic interferon in the treatment program in acute lymphoblastic leukemia in children]. AB - Soviet preparation of human leucocytic interferon (HLI) was injected to 112 children with acute lymphoblastic leukemia at different stages of the treatment program. The results obtained have evidenced that HLI produces a direct antitumor effect, intensifies the effectiveness of inductive chemotherapy and the treatment program leading to the prolongation of the remission period and survival of the patients, as well as induces activation of natural and antitumor resistance of the body. PMID- 2583461 TI - [Circulating granulomonocytic precursor cells and phenotype of peripheral blood monocytes in premature infants]. AB - The functional state of granulomonocytic hemopoietic stem cells was investigated in 72 premature infants in the neonatal period. New data were obtained on the concentration of committed granulomonocytic precursors, and on the characteristics of the phenotype of monocytes--the final differentiation component of this series. These data have verified the present notions on the features of nonspecific adaptation reactions in premature newborns. PMID- 2583462 TI - [Lymphocyte subpopulations in the bone marrow of children]. AB - Blood lymphocyte subpopulations, and bone marrow aspiration and biopsy materials were comparatively investigated in 10 children without hematologic or infectious diseases (the children had chest deformations and diaphragmatic hernias). Lymphocyte typing was conducted by the method of continuous cytofluorometry in a complete leucocyte suspension with the use of monoclonal antibodies. The results of the study have evidenced that the content of lymphocytes carrying T-cell markers in the aspiration material was twofold lower, and in the biopsy material fourfold lower than in the peripheral blood. The number of immature T-lymphocytes in the bone marrow is higher than their content in the peripheral blood. A total of 40% of aspiration cells and 60% of biopsy cells present in the lymphocytic window, do not carry lymphocytic markers. CD8+-lymphocytes prevail in the bone marrow. PMID- 2583464 TI - [Time course of the development of acute T-cell lymphoblastic leukemia in a 4.5 year-old child]. PMID- 2583463 TI - [Two-dimensional size-charge distribution of bone marrow cells in children with chronic immune neutropenia]. AB - Physical characteristics of bone marrow cells of normal donors were comparatively studied with those of children with immune neutropenia. As a result of the bone marrow cell separation in the density gradient according to their sedimentation rate, fractions enriched with cells of one histogenetic series (lymphoid, erythroid and granulocytic) were obtained. Electrophoretic mobility of immature granulocytes in normal donors differed from that in children with immune neutropenia. PMID- 2583465 TI - [Experience in the use of plasmapheresis in children with hemorrhagic vasculitis]. PMID- 2583466 TI - Estradiol-17 beta silastic implants in female Rana ridibunda depress thyroid hormone concentrations in plasma and the in vitro 5'-monodeiodination activity of kidney homogenates. AB - Estradiol-17 beta containing silastic tubings were implanted in female Rana ridibunda. Preliminary data, concerning in vitro incubations of such tubings in saline media, revealed that high concentrations of estradiol were released out of the tubings in the incubation medium. Compared to control-implanted frogs, the frogs that had the estradiol tubings implanted for 30 days showed a significant increase of the plasma estradiol concentration, the ovarian estradiol concentration, and the weight of the oviduct. Plasma triiodothyronine (T3) levels, plasma thyroxine levels, and the in vitro T3 production in the kidney homogenates were significantly decreased. These results indicate that high estradiol levels not only influence the gonadal axis, but also cause important effects on the thyroidal axis. PMID- 2583467 TI - Pineal activity during the seasonal gonadal cycle in a wild avian species, the tree pie (Dendrocitta vagabunda). AB - The aim of the present investigation was to study the pineal activity during the seasonal gonadal cycle in both sexes of the Indian tree pie (Dendrocitta vagabunda). The findings revealed that the nuclear diameter of the pineal parenchymal cells moderately decreased and was followed by a moderate increase in the cell population density (per microscopic field of the pineal sections) and serotonin content of the gland during the progressive phase. The values of these parameters were further altered (decreased nuclear diameter with increased cell population density and serotonin level) during breeding but were reversibly altered to some extent during the regression phase, and further altered during the nonbreeding phase in both sexes of the birds. It is suggested that the pineal activity distinctly varies with the seasonal gonadal cycle, being minimum during breeding and maximum during nonbreeding in both sexes of the tree pie. PMID- 2583469 TI - Sex differences in the profiles of prothoracic gland synthetic activity and of hemolymph ecdysteroid titers during development in the last larval instar of Rhodnius prolixus (Hemiptera). AB - The synthesis of ecdysteroids by prothoracic glands (PGs) of Rhodnius prolixus was measured in vitro by radioimmunoassay in both male and female larvae following initiation of development in the last larval instar by a blood meal. Neither ecdysteroid synthesis nor hemolymph titer differ between the sexes during the first few days following a blood meal. However, on Day 4 the PGs of female larvae commence a surge of increased synthesis, while in males this surge does not commence until Day 5. This 1 day difference is attributed to different times of activation of the PGs by prothoracicotropic hormone in male and female larvae. From Day 4 onward, differences between male and female larvae are described for both ecdysteroid synthesis and titer, both of which are more complex than a 1-day displacement of duplicate profiles. Both temporal and quantitative differences are detailed between males and females during Days 4-16 of development; ecdysteroid synthesis by PGs varies between males and females by up to fourfold on the same day. The hemolymph ecdysteroid titer profile closely follows that of PG synthesis for each sex. Both PG activity and titer in females decline 1 day ahead of males. The declining titer is known to influence the timing of ecdysis, and it was found that the median ecdysis time of females occurs 1 day before that of males even when males and females are synchronized with each other using a developmental marker on Day 14. We conclude that male and female PGs possess the intrinsic ability to synthesize ecdysteroids in a sex-specific pattern during development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583468 TI - Influence of human urinary erythropoietin and L-thyroxine on blood morphology and energy reserves in two tropical species of fed and starved teleosts. AB - Erythropoietic responses of fed and starved species of teleosts, viz., Clarias batrachus and Heteropneustes fossilis, to human urinary erythropoietin and thyroxine have been examined. The effects of these hormones on energy reserves have also been evaluated. Twenty-four C. batrachus were divided into two groups: half were fed regularly; the remaining fish were starved 20 days. On the 21st day each group was further divided into three subgroups of four each and received either saline, thyroxine (8 micrograms), or erythropoietin (6 IU) over 4 consecutive days. The experimental protocol was identical for H. fossilis; however, for H. fossilis two identical studies were conducted approximately 1 year apart. A decline in the rate of erythropoiesis and a stimulatory response to human urinary erythropoietin followed starvation in both species of teleosts. In addition, erythropoietin had a pronounced effect on hepatic glycogenesis of fed H. fossilis and stimulated erythropoiesis in the fed teleosts of both species. Prolonged starvation drastically depleted hepatic glycogen in C. batrachus. In contrast, it had no effect on hepatic glycogen in H. fossilis and on muscle glycogen and protein in both species. In general, while both species could respond to erythropoietin and withstand prolonged starvation, H. fossilis alone exhibited remarkable tolerance to fasting. PMID- 2583471 TI - Calcitonin gene-related peptide in neural tissues: a phylogenetic study. AB - A heterologous radioimmunoassay using a rabbit antiserum raised against human calcitonin gene-related peptide (CGRP) was used to measure levels of immunoreactive CGRP (IR-CGRP) in the brain, pituitary, and spinal cord in species representing all classes of vertebrates from cyclostomes to mammals, except amphibians. All the brain extracts except those from the trout, goldfish, and iguana demonstrated the presence of IR-CGRP. Pituitary extracts from all animals, except the ratfish, goldfish and trout, contained IR-CGRP. CGRP was present in all classes of animals tested and seems to be highly conserved in the nervous system, where it may act as a neurotransmitter or neuromodulator. PMID- 2583470 TI - Blood steroid levels in the goldfish: measurement of six ovarian steroids in small volumes of serum by reverse-phase high-performance liquid chromatography and radioimmunoassay. AB - A reliable and rapid technique for the measurement of estradiol-17 beta, testosterone, progesterone, 17 alpha-hydroxyprogesterone, 17 alpha,20 beta dihydroxy-4-pregnen-3-one, and cortisol by reverse-phase high-performance liquid chromatography and radioimmunoassay in single female goldfish serum samples of 50 microliters was developed. The steroids were extracted with Sep-Pak C18 cartridges after heat treatment. While estradiol-17 beta was assayed directly after extraction, the other steroids were separated on a mu Bondapak C18 stainless-steel column with acetonitrile:water (53:47, v/v) in 17 min under isocratic conditions, and then quantitated by specific radioimmunoassays. The technique was validated and was shown to be highly accurate, precise, sensitive, and specific for measuring those particular ovarian steroids in goldfish serum. The steroid levels measured in this way were not significantly different from those measured after separation on a Nova-Pak C18 column with methanol:water (56:44, v/v), where all the individual steroids could be completely resolved during a 40-min run. With this technique, the steroid levels in the serum of the goldfish during the secondary yolk stage, the tertiary yolk stage, and at 0 hr after ovulation were determined. While estradiol-17 beta was found to be significantly higher in the tertiary yolk stage, testosterone was significantly higher in the secondary yolk stage than in the other two stages. There was no significant difference in the levels of cortisol, 17 alpha-hydroxyprogesterone,17 alpha,20 beta-dihydroxy-4-pregnen-3-one, and progesterone among the three stages. We conclude that the technique is particularly useful for assaying multiple steroids in very small volumes of biological fluids. PMID- 2583472 TI - Inherited changes in concentrations of retinal and serum melatonin in the chicken. AB - Concentrations of melatonin in the retina, serum, and pineal gland were studied in genetically blind chicks carrying an autosomal recessive mutation, rc, characterized by the degeneration of photoreceptors in the retina after hatching. Blind homozygous (rc/rc) and sighted heterozygous (Rc+/rc) chicks were housed under 12:12 light:dark cycles. They were decapitated at 4, 6, 8, and 10 weeks of age at midlight and middark. Retinas, pineal glands, and serum samples were collected, and the resultant tissue melatonin was extracted and determined by radioimmunoassay. Retinal and pineal melatonin were also identified and quantified by gas chromatography-mass spectrometry (GC-MS). Good correlations were demonstrated between the values obtained by GC-MS and levels of quantified by radioimmunoassay. In all the tissues studied, there were age-related changes and diurnal variations in melatonin levels with high levels in the dark period. Melatonin levels in the retina and serum of rc/rc chicks were also significantly lower than those of Rc+/rc control birds. However, storages of melatonin in the pineal gland were similar between the two groups of chicks studied. These results suggest that (1) retinal melatonin is synthesized in the photoreceptor, (2) the phototransduction process which produces neural signals (i.e., electroretinogram) may be different from the phototransduction process which initiated the rhythmic melatonin synthesis and production in the retina, (3) the inherited degeneration of retinal photoreceptors with lower retinal melatonin levels correlates with an inherited abnormality of the pineal melatonin synthesis and/or secretion resulting in lower serum melatonin levels (pleiotropism), (4) levels of pineal melatonin (an indicator of the rate of synthesis and/or storage) and that of serum melatonin (an indicator of the rate of release) may not be directly correlated, and (5) the chicken pineal secretes melatonin not only by simple diffusion but also from a bound pool of melatonin in the gland. PMID- 2583473 TI - Changes in tissue and blood concentrations of thyroid hormones in developing chum salmon. AB - The changes in tissue and blood concentrations of thyroxine (T4) and triiodothyronine (T3) were examined during development of the chum salmon (Oncorhynchus keta). Extraction methods previously established for tissue T4 were also validated for tissue T3, by parallel displacement curves to T3 standard in the radioimmunoassay and by the same elution patterns of immunoreactivity in a HPLC system. The T3 concentration of the eggs just after fertilization (4-9 ng/g) was lower than the T4 concentration (5-15 ng/g). Both T4 and T3 concentrations in the whole body decreased steadily during yolk absorption, primarily due to the decline of the hormone content in the yolk. Both T4 and T3 were detected in blood plasma at later stages of yolk absorption, and the plasma levels increased toward the end of yolk absorption. At the end of yolk absorption, when the larvae emerge from the gravel bed, a transient increase in whole body concentrations of T4 and T3 was observed. Plasma levels of T4 were always greater than the T3 levels. Thyroid follicles began to develop during the early stages of yolk absorption. These findings suggest important roles of maternal thyroid hormones for developing salmon embryos during yolk absorption. PMID- 2583474 TI - Ovarian and adrenal function in the parthenogenetic whiptail lizard Cnemidophorus uniparens in the field and laboratory. AB - The purpose of this study was to document circulating concentrations of corticosterone in the plasma in relation to the ovarian follicular cycle in animals in the field and to examine the effects of captivity and laboratory manipulations on plasma corticosterone in the parthenogenetic whiptail lizard Cnemidophorus uniparens. In nature, circulating concentrations of corticosterone are highest in previtellogenic individuals when concentrations of progesterone are basal and estradiol-17 beta is undetectable. In vitellogenic lizards, circulating concentrations of corticosterone decline from previtellogenic levels while concentrations of progesterone and estradiol-17 beta increase. In preovulatory individuals, corticosterone concentrations are basal, while progesterone and estradiol-17 beta levels are maximal. Following ovulation, corticosterone and progesterone remain at preovulatory concentrations and estradiol-17 beta is undetectable. Ovariectomy elevates circulating concentrations of corticosterone, as does cold and handling. Individuals housed either in isolation or in groups of three per cage exhibit circulating concentrations of corticosterone similar to those measured in the plasma of animals immediately after being captured in the field. The effects of ovariectomy and cold/handling manipulations were additive. No nonadditive effect (statistical interaction) was revealed. These results document complementary and reciprocal effects of ovarian and adrenal gland function with respect to hormonal changes both in the field and as a result of experimental manipulations in the laboratory. However, relationships between ovarian and adrenal function appear to be complex. Several overlapping hypotheses are offered as possible explanations of the results and as potential avenues for further investigations. PMID- 2583475 TI - The effects of estradiol and testosterone on mullerian-duct regression in the American alligator (Alligator mississippiensis). AB - Female hatchling alligators were castrated and implanted with a graft of either skeletal muscle tissue or testicular tissue from male hatchlings. Following surgery, each female also received a sustained-release pellet (Innovative Research of America, Rockville, MD) implanted subcutaneously that delivered one of the following treatments: a control substance (0.1 mg), 17 beta-estradiol (0.01 mg), or testosterone propionate (0.1 mg). Treated and final control females were sacrificed 8 weeks after surgery, and the mullerian and wolffian ducts were removed and examined histologically. The testis graft induced regression of the mullerian ducts in both the testosterone- and control-treated females. In the estradiol-treated females, however, no mullerian-duct regression occurred, indicating that estradiol prevented testis-induced regression. In the females that received a muscle graft, the mullerian ducts of placebo-treated females were morphologically similar to those of the intact final control females, but they were smaller in size. On the other hand, estradiol-treated mullerian ducts exhibited significant hypertrophy, but differentiation of muscle tissue in the stroma was not induced. Some of the testosterone-treated ducts were also slightly stimulated, but none showed any signs of regression. This suggests that testosterone does not induce regression in this species. Finally, there was no effect of either graft treatment or steroid treatment on the wolffian ducts. The evolutionary significance of these results is discussed. PMID- 2583476 TI - Transformation of Bacillus thuringiensis vegetative cells by electroporation. AB - A highly efficient procedure for the transformation of Bacillus thuringiensis and Bacillus subtilis using covalently closed circular plasmid DNA was developed by using the small Staphylococcus aureus plasmid pC194 and electroporation. We have achieved transformation efficiencies in B. thuringiensis subsp. kurstaki (HD-73) greater than 5 x 10(6) transformants/micrograms plasmid DNA. The electro transformation (or electroporation) procedure also worked with B. subtilis 168 although at a 200-fold less level of efficiency. The results indicated that the plasmid exists in double and single-stranded forms both in B. subtilis and B. thuringiensis. A second single-stranded species was also observed in both species. This technique may prove to be applicable to other members of the genus Bacillus. PMID- 2583477 TI - Temperature-dependent incorporation of 4-amino-L-arabinose in lipid A of distinct gram-negative bacteria. AB - The presence and the relative amount of 4-amino-L-arabinose in lipopolysaccharides of members of the Enterobacteriaceae family and in a single strain of Chromobacterium violaceum has been studied with regard to growth temperature dependent variations. Changes in the presence and the amount of 4 amino-L-arabinose (4-AA) were observed in almost all cases, but the variations observed were not consistent among different species. While Salmonella minnesota and Proteus mirabilis showed higher levels of incorporation at higher temperatures, the S- and R-forms of Yersinia enterocolitica showed the opposite effect, i.e. only marginal incorporation by growth at 10 degrees C. Chromobacterium violaceum, however, showed no significant alteration in the 4 amino-L-arabinose content when growth either at 14 or at 37 degrees C. DOC-PAGE pattern of isolated lipopolysaccharides showed characteristic profiles indicating that the O-chain-synthesis of distinct Enterobacteriaceae is also differently influenced by changes in growth temperature. PMID- 2583478 TI - Antibiotic resistance mutations in the chloroplast 16S and 23S rRNA genes of Chlamydomonas reinhardtii: correlation of genetic and physical maps of the chloroplast genome. AB - Mutants resistant to streptomycin, spectinomycin, neamine/kanamycin and erythromycin define eight genetic loci in a linear linkage group corresponding to about 21 kb of the circular chloroplast genome of Chlamydomonas reinhardtii. With one exception, all of these mutants represent single base-pair changes in conserved regions of the genes encoding the 16S and 23S chloroplast ribosomal RNAs. Streptomycin resistance can result from changes at the bases equivalent to Escherichia coli 13, 523, and 912-915 in the 16S gene, or from mutations in the rps12 gene encoding chloroplast ribosomal protein S12. In the 912-915 region of the 16S gene, three mutations were identified that resulted in different levels of streptomycin resistance in vitro. Although the three regions of the 16S rRNA mutable to streptomycin resistance are widely separated in the primary sequence, studies by other laboratories of RNA secondary structure and protein cross linking suggest that all three regions are involved in a common ribosomal neighborhood that interacts with ribosomal proteins S4, S5 and S12. Three different changes within a conserved region of the 16S gene, equivalent to E. coli bases 1191-1193, confer varying levels of spectinomycin resistance, while resistance to neamine and kanamycin results from mutations in the 16S gene at bases equivalent to E. coli 1408 and 1409. Five mutations in two genetically distinct erythromycin resistance loci map in the 23S rDNA of C. reinhardtii, at positions equivalent to E. coli 2057-2058 and 2611, corresponding to the rib3 and rib2 loci of yeast mitochondria respectively. Although all five mutants are highly resistant to erythromycin, they differ in levels of cross-resistance to lincomycin and clindamycin. The order and spacing of all these mutations in the physical map are entirely consistent with our genetic map of the same loci and thereby validate the zygote clone method of analysis used to generate this map. These results are discussed in comparison with other published maps of chloroplast genes based on analysis by different methods using many of the same mutants. PMID- 2583479 TI - A new kind of informational suppression in the nematode Caenorhabditis elegans. AB - Independent reversions of mutations affecting three different Caenorhabditis elegans genes have each yielded representatives of the same set of extragenic suppressors. Mutations at any one of six loci act as allele-specific recessive suppressors of certain allels of unc-54 (a myosin heavy chain gene), lin-29 (a heterochronic gene), and tra-2 (a sex determination gene). The same mutations also suppress certain alleles of another sex determination gene, tra-1, and of a morphogenetic gene, dpy-5. In addition to their suppression phenotype, the suppressor mutations cause abnormal morphogenesis of the male bursa and the hermaphrodite vulva. We name these genes smg-1 through smg-6 (suppressor with morphogenetic effect on genitalia), in order to distinguish them from mab (male abnormal) genes that can mutate to produce abnormal genitalia but which do not act as suppressors (smg-1 and smg-2 are new names for two previously described genes, mab-1 and mab-11). The patterns of suppression, and the interactions between the different smg genes, are described and discussed. In general, suppression is recessive and incomplete, and at least some of the suppressed mutations are hypomorphic in nature. A suppressible allele of unc-54 contains a deletion in the 3' noncoding region of the gene; the protein coding region of the gene is apparently unaffected. This suggests that the smg suppressors affect a process other than translation, for example mRNA processing, transport, or stability. PMID- 2583480 TI - Distinguishing the forces controlling genetic variation at the Xdh locus in Drosophila pseudoobscura. AB - Fifty-eight isochromosomal lines sampled from two natural populations of Drosophila pseudoobscura in California and one from Bogota, Colombia, were examined using four-cutter restriction mapping. A 4.6-kb region of the xanthine dehydrogenase locus was probed and 66 of 135 restriction sites scored were polymorphic. This predicts that on average every 12th bp would be polymorphic in this region for the genes surveyed if polymorphism occurred randomly along the coding region. In addition, there were 12 insertion/deletion polymorphisms. Forty nine distinct haplotypes were recognized in the 58 lines examined. The most common haplotype obtained a frequency of only 5%. Measures of base pair heterozygosity (0.0097) and linkage disequilibrium lead to a predicted population size in the range of 1.2-2.4 X 10(6) for the species. High levels of recombination (including gene conversion) can be inferred from the presence of all four gametic types in the data set. PMID- 2583481 TI - Genetic mapping in Xenopus laevis: eight linkage groups established. AB - Inheritance of alleles at 29 electrophoretically detected protein loci and one pigment locus (albinism) was analyzed in Xenopus laevis by backcrossing multiply heterozygous individuals generated by intersubspecies hybridization. Pairwise linkage tests revealed eight classical linkage groups. These groups have been provisionally numbered from 1 to 8 in an arbitrarily chosen order. Linkage group 1 includes ALB-2 (albumin), ADH-1 (alcohol dehydrogenase), NP (nucleoside phosphorylase), and ap (periodic albinism). Linkage group 2 contains ALB-1 and ADH-2, and probably is homeologous to group 1. Linkage group 3 comprises PEP-B (peptidase B), MPI-1 (mannosephosphate isomerase), SORD (sorbitol dehydrogenase), and mIDH-2 (mitochondrial isocitrate dehydrogenase). Linkage group 4 contains GPI 1 (glucosephosphate isomerase) and EST-4 (esterase 4). Linkage group 5 contains GPI-2 and PEP-D (peptidase D). Linkage group 6 comprises ACP-3 (acid phosphatase), sME (cytosolic malic enzyme), and GLO-2 (glyoxalase). Linkage group 7 consists of sSOD-1 (cytosolic superoxide dismutase), GPD-2 (glycerol-3 phosphate dehydrogenase), mME (mitochondrial malic enzyme), and the sex determining locus. Linkage group 8 includes FH (fumarate hydratase) and TRF (transferrin). Recombination frequencies between linked loci showed differences related to the genomic constitution (parental subspecies) and to the sex of the heterozygous parent. Independent assortment was observed between the duplicate ALB loci. This is true for the duplicate ADH, GLO, and MPI loci as well, supporting the view that these genes have been duplicated as part of a genome duplication that occurred in the evolutionary history of X. laevis. Comparative analysis of genetic maps reveals a possible conservation of several linkages from the Xenopus genome to the human genome. PMID- 2583482 TI - Mitochondrial and nuclear gene dynamics of introduced populations of Lepomis macrochirus. AB - A population of bluegill sunfish, Lepomis macrochirus, was introduced into three man-made ponds in 1966. Analyses of these ponds in 1984 and 1985 found significant mtDNA divergence without nuclear gene differentiation. The difference between nuclear gene and mtDNA measures of interpopulational divergence was very large and suggests that sexual asymmetries in life histories may be important considerations in mtDNA and nuclear gene rates of divergence. The rapid divergence of mtDNA haplotype frequencies suggests that sorting of previously existing variation may accelerate mtDNA divergence among recently isolated populations. PMID- 2583484 TI - [A phylogenetic analysis of genes of the influenza virus. Phylogenetic trees and fixation rates]. AB - The phylogenetic trees of influenza virus genes of hemagglutinins, neuraminidases, and of NS genes were composed. Considering properties of synonimic replacements to be neutral and their rates constant at each tree, the dates of ancestor branch points were calculated, and the rates of fixation of synonimic (Ks) and non-synonimic (Kns) replacements estimated. The epidemic branches were mostly shown to be "deadlocks", non-epidemic ones being internal or "roots." The ratios of the numbers of synonimic to non-synonimic replacements (vs/vns) were correspondingly 1.32+/-0.42 and 4.78+/-1.28 for all trees, the difference being significant. It was shown that the dated branch points for hemagglutinins are non-randomly clustered around the initial points of the main genetic shifts of the A-type virus, corresponding to the influenza pandemics. It seems that these ancestor forms of virus behave similar to the "train" of these shifts, reproducing together with the pandemic forms under conditions of decreased immune resistance of host population. The rates of fixation of non synonimic replacements in the epidemic branches of this tree are 4 times increased, as compared to non-epidemic ones. PMID- 2583483 TI - [Nucleotide sequence of the B1-hordein gene of barley Hordeum vulgare L]. AB - The gene encoding B1 hordein of Hordeum vulgare (cv. Donetsky 4) was cloned and entirely sequenced. It contains no introns and codes for of 293 amino acids long polypeptide with molecular weight 33418. Our clone differs from the previously sequenced B1 hordein genes in some positions within the coding region (there are 4 nucleotide changes and a 12 bp deletion, as compared with the pB11 cDNA clone, and 5 nucleotide changes, as compared with the pBHP184 genomic clone). These changes result in polymorphism of amino acid sequences at 5 positions. 5' flanking region contains putative regulatory and promoter sequences and differs from that of the pBHP184 clone in 3 positions. PMID- 2583486 TI - [Cytogenetic mapping of cattle (Bos taurus L.). Quantitative analysis of the RBA map of prometaphase chromosomes]. AB - Using the decondensing effect of ethidium bromide and replicative (RBA) staining a high resolution map of cattle chromosomes was produced. The extent and distribution pattern of R(G) blocks were estimated quantitatively. The data thus obtained are correlated with the results of cytogenetic mapping in other mammalian species and in man. PMID- 2583485 TI - [Genetic control of catalepsy in mice]. AB - Pinch-induced immobility (catalepsy) was studied in mice of 9 inbred strains. CBA mice were found to be different from those of other strains both by the highest percent of cataleptics (56%) and by the highest duration of immobility. The Mendelian analysis of predisposition to catalepsy was performed on CBA and AKR mice strains contrasting in this feature. Reciprocal F1 hybrids did not display any catalepsy. Manifestation of cataleptics in the F2 and in CBA x F2 backcrosses suggested that catalepsy was inherited as a recessive, monogenic, autosomal feature. PMID- 2583487 TI - [EcoRI- and BamHI-families of repeated sequences in mustelids]. AB - The restriction enzymes EcoRI and BamHI digest the genomic DNAs from six mustelids species Mustela lutreola, M. vision, M. erminea, M. sibirica, Vormela peregusna, producing repeated fragments varying in length. Some fragments were hybridized to chromosomes and restriction digests of DNAs from some mustelids and other mammals. The 0.7 kb EcoRI repeats from DNA of M. erminea are dispersed over chromosomes of carnivors. The 1.35, 1.9 and 2.7 kb BamHI repeats from DNA of polecat M. putorius furo are specific for mustelids. These repeats demonstrate interspecific variation in length and the number of copies. All BamHI repeats have no strict tandem organization. The 1.9 kb BamHI repeats are concentrated in the heterochromatic pericentromeric regions and additional chromosome arms. The 1.35 kb BamHI repeats are only located in the centromeric regions of chromosomes of five species and are absent in Vormela peregusna. PMID- 2583488 TI - [The effect of cow genotype for beta-casein on the quantitative level of milk proteins]. AB - The quantitative content of 14 milk proteins was investigated in Bestuzhevskaya and Kholmogorskaya cows with different genotypes for beta-casein. It is shown that beta-CnA1 allele provides higher content of protein in corresponding variant, as compared to beta-CnB and beta-CnA2 (P less than 0.05-0.001). beta casein quantity in milk is in following dependence on genotypes for beta-Cn: A1B less than A1A1 greater than A1A2, A2B greater than BB greater than A2A2. The effect of locus beta-Cn on the quantity of total protein, caseins and separate milk proteins was also found (eta 2 = = 0.098-0.147). PMID- 2583489 TI - [Analysis of the interconnection between susceptibility factors to schizophrenia and epilepsy]. AB - The results of the genetic-correlative analysis of schizophrenia (681 families) and epilepsy (365 families) are given. The presence of various liabilities to these diseases, having genetic correlation of 0.16-0.19 between them, is shown. From epidemiologic data, elevated frequency of convulsive manifestations in schizophrenics and schizophrenia-like psychosis in epileptic patients was established. Within the limits of the three-component hypothesis of etiology of these diseases ("major genes", environmental factors and constitutional readiness), the relation detected is explained by interaction between constitutional readiness factors. PMID- 2583490 TI - [Isoenzymes of human blood cholinesterases and their genetic control]. AB - Acetylcholinesterase from human erythrocytes solubilized by 1% Triton X-100 was resolved using polyacrylamide gel electrophoresis into two components. The first one (fast) is more firmly bound to cell membranes than the other. The existence of multiple forms (C1-C4) of serum cholinesterase-1 (CHE1) has been established. Electrophoresis in acid medium (pH 4.8) permits to detect the C5 component and a group of supplementary isoenzymes of cholinesterase-2. Individual differences observed in patterns of the CHE2 isozymes are controlled by a pair of autosomal codominant alleles Che2A and Che2B. The serum of subjects with phenotypes Che2AB(C5+) and Che2BB(C5-) showed on the average equal level of cholinesterase activity. PMID- 2583491 TI - [Phylogenetic analysis of genes of the influenza virus. Relationship between adaptability and neutrality]. AB - Detailed phylogenetic analysis of the gene family of hemagglutinin H3 of influenza A-type virus was fulfilled, taking into account the domain structure of protein and positions of antigen determinants. The densities of distribution of fixed synonimic replacements between domains HA1 and HA2 were shown to be actually equal (rho (HA1) = rho (HA2], and those of nonsynonimic ones to be unequal: their ratios were rho (HA1): rho (HA2) = 2.8 for nonepidemic branches, and rho (HA1): rho (HA2) = 7.7 for epidemic ones. For the positions of antigen determinants (agd) these densities differ still stronger from HA2: rho (agd): rho (HA2) = 10 for nonepidemic branches, and rho (agd): rho (HA2) = 36 for epidemic ones. In total, the rate of fixation of nonsynonimic replacements per position of antigen determinants for epidemic branches is 32 times higher than for nonepidemic ones. The absolute value of this estimation is K(ns)d = (9.1 +/- 0.7).10(-3) of nonsynonimic replacements per nonsynonimic position per year and seems to be twice as much as the maximum rate of neutral fixations Ks = (4.28 +/- 0.68).10(-3). Therefore, the epidemic reproduction of influenza virus is highly adaptive, exactly being focused on positions of antigen determinants. The evolution of influenza virus is stochastic process, both with the neutral and adaptive fixations. PMID- 2583492 TI - [Re-evaluation of genetic formulae and epistasis]. AB - Experimental verification of some quantitative results, following from the new theory for investigation of non-allelic genes' interactions in the diallele analysis by Hayman was conducted. We postulated earlier a special kind of epistasis HC which is the new explication of epistasis j--the interaction between homozygote and heterozygote by Mather and Jinks. Genetic interpretation of the epistasis HC establishes some relations between epistasis and the model of ecological-genetical control of quantitative characters. We found the invariant characteristic of genetic control which is stable in a number of characters, environments, treatments, inspite of redetermination of genetic formulae under conditions of environmental variability. PMID- 2583493 TI - [Localization of the di gene in the fourth linkage group in Rattus norvegicus rats]. AB - Based on the backcross progeny analysis of rats Rattus norvegicus matings (August X Brattleboro)F1 X Brattleboro, the gene di has been localized in the fourth linkage group at a distance of 26.8 +/- 1.7 cM from the non-agouti loci and 11.4 +/- 4.7 cM from the Svp-1 loci. The gene order proposed is a--Svp-1--di. PMID- 2583494 TI - Bronchoprovocation challenge: update. PMID- 2583495 TI - Environmental challenge. AB - A variety of organic dusts and chemicals encountered in our environment are capable of provoking a response in the lung. Frequently, they produce transient or reversible physiologic changes that may obscure the diagnosis. The patient may fail to recognize a causal relationship with a specific exposure with late-onset reactions and the development of symptoms remote from the exposure. A thorough evaluation of the individual's total environment and symptoms, with particular reference to their time course, is essential in making the diagnosis. Removal of the worker from a suspected environment, with serial clinical and physiologic monitoring to demonstrate improvement, or return to the workplace with similar studies, can be helpful in establishing a causal relationship. When a specific agent can be identified, a controlled inhalation challenge in the laboratory is the procedure of choice. Once a causal relationship has been established, the individual should be removed from exposure or the implicated agent eliminated. PMID- 2583497 TI - [Bacteriologic studies of flies and cockroaches in the residential quarters of refuse disposal sites in Cairo (Mokattam and Ezbeth el Nakhl)]. AB - In Cairo's waste disposal sites various germs could be isolated from cockroaches and flies; antibiotic resistance was determined. PMID- 2583496 TI - Ocular infection investigations in Cairo's waste disposal sites. PVP-iodine treatment trials. AB - Investigations were carried out in Cairo's waste disposal sites of the inhabitants of all age groups. Germ-spectrum was analyzed before and after PVP Iodine-treatment. However, any further dilution of PVP-Iodine in the treatment had no effect on the germspectrum, as hydrochloric acid formation in air, produced by plastic burning causes severe eye irritation and a constant lacrimation. The high germ count of the air in the dwellings and the environment is an additional source of contamination to the conjunctiva. PMID- 2583498 TI - Leptospirosis in man, in wild and in domestic animals at waste disposal sites in Cairo. AB - The authors examined 65 Rattus rattus, 28 pigs, 12 donkeys, 67 goats, 5 sheep, 1 cow and 1 dog as well as 196 inhabitants at two settlements on the waste disposal sites at the periphery of Cairo. Rattus norvegicus were positive in 55.4% for L. ictero-haemorrhagiae, pigs in 14.3% for L. pomona and in 3.6% for L. ictero haemorrhagiae. 2 out of 12 donkeys were positive for L. pomona, 1 of them for L. pyrogenes and L. icterohaemorrhagiae as well, goats in 1.5% for L. grippotyphosa. Human sera reacted positively in 8.7% of the cases, 7.1% of which with L. bratislava, 1.0% with L. icterohaemorrhagiae and 0.5% with L. grippotyphosa and L. sejroe respectively. PMID- 2583499 TI - [Serologic studies of listeriosis antibodies in dogs in Greece]. AB - In an epidemiological study of dogs carried out in Greece, antibodies against listeriosis were demonstrated in the slow-agglutination and the complement fixation-reaction. Depending on the dogs' place of origin CFR titers were found in 6.1% to 51.1%. CFR-titers could be confirmed in a comparative investigation with the slow-agglutination-test. PMID- 2583500 TI - Medical entomology problems of people working in Cairo's waste disposal sites. PMID- 2583501 TI - [Toxoplasmosis in dogs in Greece]. AB - In Greece, not only raw meat feeding but also the possible faecal transmission of disease from the vast amount of strayed domestic cats play an important role in the incidence of toxoplasmosis among dogs. This must be concluded from the high contamination rate of 21.2% to 30.8% in all four presented investigations. PMID- 2583502 TI - [Studies of dog sera using the microagglutination test for Q-fever in Greece]. AB - In serological investigations of dog sera from Greece for Q-fever 4.2% to 53.9% of samples were positive in the highly specific microagglutination test. PMID- 2583503 TI - [Leptospirosis in dogs in Greece]. PMID- 2583504 TI - [Transmission of visceral leishmaniasis with studies of dogs in Greece]. AB - According to our results the public fear in Greece of infection from dogs or the dog as a possible reservoir could not be confirmed. A total of 749 dogs were investigated. Positive findings were demonstrated successfully in 10 cases of 19 clinical cases and serologically confirmed in 10 cases. Strains were isolated in the experimental animal the hamster. PMID- 2583505 TI - Serological investigations for leptospirosis in humans in Columbia. AB - The authors examined serologically 353 clinically healthy persons in 5 localities in South Columbia for leptospirosis using the MAL-reaction with 15 serovars of 15 serogroups. The positivity was high - 18.4% namely with the serovars of the serogroups Icterohaemorrhagiae, Canicola, Pyrogenes, Australis, Pomona, Grippotyphosa, Sejroe, Hebdomadis, Bataviae, Panama and Shermani. Sera reacted positive in titer levels of 1:400 and higher only with the serovars of the serogroups Icterohaemorrhagiae, Canicola, Australis, Grippotyphosa, Sejroe, Hebdomadis, Panama and Shermani. In the total positivity were the serovars of the serogroups Icterohaemorrhagiae with 30.8%, Grippotyphosa with 23.1%, Australis with 15.4%, Panama and Pyrogenes with 10.8% each, Pomona with 6.2%, Shermani with 4.6% and Canicola, Sejroe, Hebdomadis, Bataviae with 3.1% each. The high positivity of the sera from the Mocoa for L.grippotyphosa was surprising - 20.7%. PMID- 2583506 TI - Results of leptospirosis examinations of human sera from El Salvador. AB - The authors examined 984 human sera for leptospirosis with the serovars from 15 serogroups serologically in 15 localities of El Salvador. In 17.5% of the sera the following reactions were found with serovars of 13 serogroups: Australis 6.8%, Pomona 5.5%, Grippotyphosa 3.2%, Icterohaemorrhagiae and Tarassovi each 2.1%, Javanica, Canicola, Pyrogenes, Cynopteri, Autumnalis, Sejroe, Hebdomadis, Bataviae, Shermani, between 0.2%-1.4%. Men showed a 18.5% and women 17.0% positive reaction. Positivity increases with an increase in age, an increase was shown from 11.5% in the group of up to 10 years, to 40.4% in the group of 51 to 60 years, in the last age group of over 60 years a decrease was shown of 34.7%. In 8 localities we were able to compare the serological positivity of the population, the highest percentages were found in Fey Esperanza 35.1%, San Jose de la Montana 31.6% and Domus Maria 27.8%, the lowest in Credisa 6.4% and Ametepec 7.6%. PMID- 2583507 TI - [The significance of detecting Corynebacterium equi in the conjunctiva of children in Cairo]. AB - The probable correlations between certain Corynebacterium are discussed. Carpenter et al. (1976) describes a Corynebacterium equi-pneumonia in a patient with Hodgkin's disease; Gardner et. al. (1976) also reports on a case of pneumonia. Golub et. al. (1967) demonstrates a lung abscess resulting from Corynebacterium equi. Williams et. al. (1971) demonstrates a thoracic infection in an immunosuppressed patient. Although, our findings have been demonstrated only in conjunctivitis of children, hitherto descriptions of Corynebacterium equi in diseases of the lungs, especially in the case of a low immune response in certain sections of the population should be taken into account. Further investigations of the numerous dead donkeys with severe clinical symptoms of lung sequela are necessary. PMID- 2583508 TI - [Data from measuring air pathogens of inhabitants of refuse disposal sites in Cairo (1)]. AB - Atmospheric germ measurements were carried out and the germ spectrum determined in medical ambulances, bedrooms and livingrooms. PMID- 2583509 TI - Continentality indices patterns in Greece. AB - Two continentality indices patterns in Greece are presented in this paper by using the Conrad's and Kerner's formulas. PMID- 2583510 TI - Climate and bioclimate of the broader region of the spas at Kamena Vourla, Thermopylae, Hypati and Aedipsos and their hydrotherapeutical possibilities. AB - The climate and bioclimate of spas in the central region of Greece are examined in this paper. Besides, the hydrotherapeutical possibilities of the spas at Kamena Vourla, Thermopylae, Hypati, Aedipsos and Platystomo are determined. PMID- 2583511 TI - Purification and characterization of the FokI restriction endonuclease. AB - The restriction endonuclease FokI from Flavobacterium okeanokoites was purified to homogeneity. Based on gel filtration, sedimentation and sodium dodecyl sulfate polyacrylamide-gel electrophoresis, the following properties of the enzyme were determined: FokI exists in one active monomeric form, and has an Mr of 64-65.4 x 10(3).FokI is a strongly basic protein with an isoelectric point of 9.4. The enzyme exhibits restriction activity in the pH range 5.0 to 10.5 (maximum level at pH 7.0-8.5) and its divalent cation requirement is satisfied not only by Mg2+, but also by Co2+, Mn2+, Ni2+, Cd2+, Zn2+ and Fe2+. PMID- 2583512 TI - The Cucurbita maxima ribosomal DNA intergenic spacer has a complex structure. AB - The nucleotide (nt) sequence of the 5508-nt intergenic spacer (IGS), between the 25S- and the 18S-coding regions of Cucurbita maxima rDNA, was determined. The fragment sequenced is 6142 nt long and includes 472 nt of 25S- and 162 nt of 18S coding regions. The IGS has a complex primary structure, composed of five repetitive families (A-E) and three unique domains. It is dominated by the presence of nine, tandemly-repeating units of approximately 250 nt (repeat D), each unit containing four copies of an internal subrepeat (repeat E). The repetitive units show sequence variability consisting of nt changes, insertions and deletions. Upstream of the nine D repeats and between two copies of the B repeat is a 575-nt region, highly G + C rich (83%) and heavily biased toward C (58%) in the sense strand. Within this region are six repetitive units, averaging 42 nt (repeat C) each, containing but a single A nt. Downstream from the terminus of the 25S-coding sequence, are two tandem copies of the 103-nt A repeat. The IGS of C. maxima is longer and more complex than that of other plant IGSs described to date. The 600 nt at the 5' portion of cucurbit IGS is more conserved in evolution than the remainder, as revealed by comparison of C. maxima and C. pepo IGS restriction maps and by nucleotide sequence comparison of C. maxima and Cucumis sativa IGSs. PMID- 2583513 TI - Analysis of distal flanking regions of maize 19-kDa zein genes. AB - Two genomic fragments from maize, each containing a 19-kDa zein gene with extensive flanking regions, have been sequenced and examined by computer-aided analysis and Southern blotting techniques. Sequence analysis of the distal flanking sequences has revealed interesting sequence motifs, some not seen before. In particular, four nearly identical, G + C-rich, 17 to 21-bp perfect palindromes were found clustered in a 133-bp stretch lying 2 kb upstream from the zein-coding region in the genomic clone pMS2. These palindromic sequences exhibit other interesting features, including a precise spatial organization with respect to each other, and their proximity to several other repeated motifs in the same region. Southern blot analysis indicates that these palindromes, or closely related sequences, are found frequently in the maize genome. Possible secondary structures for the palindrome units are presented, which resemble functionally important sequences found upstream from other eukaryotic genes. PMID- 2583514 TI - The nucleotide sequence of a microvitellogenin encoding gene from the tobacco hornworm, Manduca sexta. AB - A microvitellogenin (mVg)-coding gene (mvg) has been isolated from a lambda phage library prepared from the tobacco hornworm, Manduca sexta. One of the lambda clones had a 15-kb insert and contained the entire mvg gene. A DNA fragment (3.0 kb) containing this mvg gene has been sequenced. Southern blot analysis showed that there may be more than one mvg gene in M. sexta. The putative transcriptional start point (tsp) for the cloned mvg was determined by primer extension analysis. This gene contains a single intron in the 5'-noncoding region. The 5'-flanking sequence was compared to the 5'-conserved regions of yolk polypeptide-encoding genes (yp) of Drosophila melanogaster. Two regions were found in the 5'-flanking sequence of the mvg gene that have 66% similarity to the D. melanogaster yp consensus sequence that is believed to be involved in gene expression controlled by ecdysteroids. Furthermore, the sequences flanking these two regions are also similar to the ecdysone-responsive elements found in several genes of D. melanogaster. In fact, preliminary experiments showed that mVg mRNA synthesis is induced by the 20-hydroxyecdysone. Four regions of the mvg gene resemble the upstream conserved regions of the two vitellogenin-encoding genes of the locust, Locusta migratoria. The nucleotide sequence of mvg has 70% similarity to the sequence of one or more of the 30-kDa hemolymph proteins of Bombyx mori. This indicates a very close evolutionary relationship between these proteins. PMID- 2583515 TI - Cloning of a housekeeping-type gene (MER5) preferentially expressed in murine erythroleukemia cells. AB - DNA complementary to mRNA preferentially produced in murine erythroleukemia (MEL) cells was cloned from a cDNA library of anemic mouse spleen mRNAs. An open reading frame was noted in the cloned DNA, and was tentatively designated MER5. The MER5 mRNA is abundant in three MEL cell lines, but less in other tissues or cell lines. The levels of the MER5 mRNA changed periodically during MEL cell differentiation and decreased as globin mRNA accumulated. The MER5 promoter region contained no typical TATA-like sequence, but possible target sequences for AP1, AP2, SP1 and octamer-binding protein. More interestingly, this promoter contained the duplicated CACCC boxes, which are common in the adult beta-globin promoter from many species, but uncommon for promoters of other eukaryotic genes. PMID- 2583516 TI - A new isoschizomer, BnaI, of the BamHI restriction endonuclease. AB - By assaying the yield of phage SPO1 we have identified a new restriction modification activity in the Bacillus natto B3364 strain. A class II restriction endonuclease, BnaI, isolated from the crude extract of B3364 cells was shown to be a true isoschizomer of the BamHI endonuclease. The Mr, stability and optimal conditions required for DNA digestion were determined for BnaI. Although both enzymes show the same specificity, BnaI and BamHI differ from each other in all the properties specified above. PMID- 2583517 TI - Characterization of the simian adenovirus type 30 inverted terminal repeat. AB - The presence of an inverted terminal repeat (ITR), which plays an important role in the initiation of DNA replication, is one of the characteristic properties of adenoviruses (Ads). We have established the nucleotide (nt) sequences for the ITR of simian adenovirus type 30 (SV30), a subgroup-III oncogenic virus. This repeat consists of 185 nt, representing the longest ITR found in an Ad so far. It contains multiple copies of internal repeats, as well as the consensus sequences of the putative binding sites for replication and transcription factors. The conserved features of the known ITRs are also found in SV30. Interestingly, the ITR of SV30 is more closely related to that of Ad5 (human), than to that of SA7 (simian). PMID- 2583518 TI - Nucleotide sequence and organization of full length human U4 RNA pseudogenes. AB - Two loci encoding human U4 RNA, designated U4/7 and U4/14, have been isolated and sequenced. Both are pseudogenes in that their sequences do not match any identified human U4 RNA species perfectly. The U4/7 locus harbours a full-length pseudogene of 144 bp with eight base substitutions in the structural region. This pseudogene might be derived from a hitherto unidentified human U4 RNA gene. The second locus, U4/14, has a complex structure; the structural sequence of a U4 gene has apparently been integrated into an Alu sequence. PMID- 2583519 TI - Two sequences participating in the autolytic processing of satellite tobacco ringspot virus complementary RNA. AB - Circular and multimeric forms of the satellite RNA of tobacco ringspot virus and their autolytic processing reactions are well known. They suggest replication models in which key elements are rolling circle transcription and the processing of the resulting multimeric RNA to generate the unit, 'monomeric' satellite RNA sequence. We prepared plasmids bearing two distinct sequences of the satellite RNA. Each was arranged to allow transcription of an oligoribonucleotide (r-oligo) of the polarity that is complementary to encapsidated satellite RNA. One sequence has the autolytic processing phosphodiester bond, ApG, and the other is located at a distance of about 150 nucleotide (nt) residues. The second r-oligo accomplished cleavage of the first, in a catalytic fashion. Analysis of truncated forms showed that 10 nt of the ApG junction-containing r-oligo and 46 of the endoribonucleolytic r-oligo were sufficient for recognition in the cleavage reaction. These results map the sequences involved in autolytic processing of the complementary polarity satellite RNA to two regions. PMID- 2583520 TI - Triplex DNA in plasmids and chromosomes. AB - Circular plasmids containing pyrimidine purine tracts can form both inter-and intramolecular triplexes. Addition of poly(dTC) to plasmid pTC45, which contains a (TC)45.(GA)45 insert, results in intermolecular triplex formation. Agarose-gel electrophoresis gives rise to many well-resolved bands, which correspond to 1, 2, 3, 4... plasmid molecules attached to the added pyrimidine strand. In the electron microscope these complexes appear as a rosette of petals. The mobility of these triplex-containing complexes can be retarded by the addition of a triplex-specific monoclonal antibody, Jel318. Intramolecular triplex formation can be demonstrated at pH 5 in pTC45 and also in pT463-I, a plasmid containing a segment of a crab satellite DNA with both (G)n.(C)n and (TCC)n.(GGA)n inserts. However, although the intermolecular triplex remains stable for some time at pH 8, intramolecular triplex formation only occurs at low pH. Triplexes can also be detected by an immunoblotting procedure with Jel318. This unfamiliar structure is readily demonstrated in eukaryotic extracts, but not in cell extracts from Escherichia coli. Triplexes may thus be an inherent feature of eukaryotic chromosome structure. PMID- 2583521 TI - Insertional mutagenesis using a synthetic lac operator. AB - We have developed a novel cassette for generating insertion mutants in multi-copy bacterial plasmids. The cassette consists of synthetic oligodeoxyribonucleotides (oligos) which form a DNA duplex following reconstitution in vitro, due to sequence complementarity. It contains a 21-bp segment of the lac operator (lacZo), to provide a readily detectable phenotypic marker. Bacterial colonies harboring plasmids with insertions of this cassette are blue due to constitutive expression of the lac operon resulting from titration of lac repressor molecules by plasmid-borne lacZo sequences. Synthetic oligos containing a desire sequence may be added to the cassette by complementary ends for targeted insertion into plasmids. Sequencing of the resulting insertion mutants is facilitated by using oligos within the cassette as primers for bidirectional sequencing. This allows a complete characterization of each insertion in terms of location, structure of flanking sequences, and orientation of the inserted oligo. We have used this system to construct a series of mutants in early region 1a genes of human adenovirus type 5. For this purpose we designed a cassette which had all three possible translational reading frames open when inserted in one orientation, and all reading frames closed in the other orientation. The cassette also had BamHI restriction sites at each end which could be used to 'collapse' mutants, reducing the size of each insert to 6 bp. PMID- 2583522 TI - Nucleotide sequence of the MgPa (mgp) operon of Mycoplasma genitalium and comparison to the P1 (mpp) operon of Mycoplasma pneumoniae. AB - The attachment of Mycoplasma genitalium and Mycoplasma pneumoniae to ciliated epithelium involves two surface proteins designated MgPa and P1, respectively. We have previously cloned and sequenced the P1 (mpp) operon of M. pneumoniae, and report here the use of P1-derived probes to clone and sequence a 10.4-kb region of M. genitalium DNA that, by analogy to the P1 operon, contains the MgPa (mgp) operon. The deduced amino acid sequences of the 29-kDa (ORF-1), MgPa (160-kDa) and 114-kDa (ORF-3) proteins of the MgPa operon show extensive homologies with those of the 28-kDa, P1 (170-kDa) and 130-kDa proteins, respectively, encoded by the P1 operon. The common features and homology of these operons are consistent with previous observations that the MgPa and P1 proteins share cross-reactive epitopes, as well as similar biological function. The gene order of the MgPa operon is ORF-1, MgPa, ORF-3, with intervening regions of 6 and 1 nt, respectively. A consensus ribosome-binding site (RBS) sequence is found before ORF-1 and a sequence indicative of a transcription terminator is located beyond ORF-3; the absence of such sequences adjacent to the MgPa gene suggests that the operon is transcribed as a polycistronic message. The RBS sequence is followed by sequences of dyad symmetry that have the potential to form two alternative stem and-loop structures, which could be involved in controlling initiation of translation. PMID- 2583523 TI - Differential screening of a cDNA library with cDNA probes amplified in a heterologous host: isolation of murine GRP78 (BiP) and other serum-regulated low abundance mRNAs. AB - A novel method was used to screen differentially a cDNA library for clones representing serum-regulated mRNA species of low abundance. To increase the amount of probe available for screening, the cDNA probe was cloned and amplified. Two separate cDNA 'probe' libraries were constructed in the Escherichia coli plasmid vector pDE613, using poly(A)+mRNA from murine cells at 0 and 16 h after stimulation of a G0 population. Radiolabelled plasmid DNA from each library was hybridized sequentially to colony blots of the third 'target' library, constructed with mRNA from serum-stimulated cells in the Bacillus subtilis vector pBD214. Differential screening of the target cDNA library with the two probe libraries identified novel murine cDNA clones, some representing cytoplasmic poly(A)+RNA species of low (0.01%) abundance, accumulating after serum stimulation of a quiescent mouse embryo fibroblast population. One cDNA clone was found to correspond to mitochondrial 16S rRNA and a second was identified as the murine equivalent of previously described cDNA clones for the hamster 78-kDa glucose-regulated protein (GRP78) and the rat immunoglobulin heavy-chain-binding protein. GRP78 mRNA has not previously been recognized as a serum-inducible message. PMID- 2583524 TI - An MboII/FokI trimming plasmid allowing consecutive cycles of precise 1- to 12 base-pair deletions in cloned DNA. AB - A novel trimming plasmid has been designed which allows, in a preprogrammed fashion, the precise deletion of up to 12 bp per cleavage cycle, from one end of a cloned fragment. The plasmid, which carries the dhfr gene, contains unique recognition sites for two class-IIS restriction enzymes, MboII and FokI, which are arranged in the form of a cassette, so that consecutive cleavages with these endonucleases, followed by blunting with mung bean nuclease (MB), will precisely delete 12 bp of adjacent cloned DNA. When either MboII or FokI is used alone (followed by MB), 1 or 4 bp are removed, respectively. The final step in the trimming cycle is religation of the plasmid with T4 ligase. After required number of cycles, plasmids were transformed into Escherichia coli C600, and transformants selected by resistance to trimethoprim. Since the MboII/FokI cassette remains intact during these operations, one can repeat the cycle, consisting of cleaving, MB blunting and religation, several times, each time removing up to 12 bp from the cloned target DNA. Examples are provided of one-, two- and three-cycle trimmings. PMID- 2583525 TI - Phagemid VPCS vectors for priming, cloning and sequencing. AB - A phagemid was adapted for use as the vector in the vector-primer-cloner sequencer cloning system. The use of this new vector markedly expanded the utility of this technology for the construction of cDNA libraries. Technological advantages and new capabilities include: (1) a greater number of unique restriction sites within the polylinker region; (2) the ability to produce single stranded templates for nucleotide sequencing, and (3) a convenient means to synthesize strand-specific hybridization probes. With the use of this cloning system, a rat liver cDNA library (8.56 x 10(5) recombinants from 1 microgram of poly(A)+ RNA) was rapidly (in two days) constructed. PMID- 2583526 TI - Nucleotide sequence of the 24S subgenomic messenger RNA of a vaccine strain (HPV77) of rubella virus: comparison with a wild-type strain (M33). AB - A full-length cDNA clone for the 24S subgenomic mRNA of the vaccine strain (HPV77) of rubella virus has been isolated from a cDNA library made from the RNAs of infected cells. Starting from the first Met start codon, the 24S mRNA codes for a precursor protein of 1063 amino acids (aa). This precursor encodes a capsid protein of 300 aa, and two envelope proteins, E1 (481 aa) and E2 (282 aa). Both the E1 and E2 proteins are preceded by a stretch of 21 hydrophobic aa, characteristic of a signal peptide, and each has three putative glycosylation sites in the polypeptide chains. Comparison between the structural proteins of the vaccine and the wild-type (wt; M33) strains of rubella virus, revealed that the E2 protein of the vaccine strain differs, in its apparent Mr, by approx. 3 kDa, from the wt strain. The difference could be due to decreased glycosylation of the vaccine strain E2 protein, as revealed by [3H]mannose incorporation studies. Five single-aa changes in the structural proteins occurred during the attenuation process, one each in the capsid and the E1 protein and three in the E2 protein. The change of Thr-412----Ile in the E2 protein results in the loss of a putative glycosylation site at Asn-410, which offers a plausible explanation for decreased glycosylation of the E2 protein from the vaccine strain of rubella virus. PMID- 2583527 TI - Cloning and sequencing of immunoglobulin variable-region genes using degenerate oligodeoxyribonucleotides and polymerase chain reaction. AB - A procedure is described for using the polymerase chain reaction (PCR) to amplify and clone the cDNA from mouse immunoglobulin (Ig) variable (V) regions. This method uses a set of universal 5'-oligodeoxyribonucleotide primers that are degenerate and allow for the amplification of Ig V-region sequences from gamma and mu heavy chains and from kappa light chains. Selective first-strand cDNA synthesis is performed using Ig constant region primers and then a PCR is achieved by using the appropriate universal 5'-primer. The universal Ig heavy chain primer was used to amplify the V-region cDNA from gamma and mu isotypes and the universal light-chain primer was used to amplify three separate kappa light V region sequences. This procedure was used to obtain Ig V-region gene sequences from hybridomas secreting IgG1/kappa, IgG2b/kappa and IgM/kappa isotypes. PMID- 2583528 TI - Operon structure and nucleotide homology of the chlorocatechol oxidation genes of plasmids pJP4 and pAC27. AB - Alcaligenes eutrophus harboring plasmid pJP4 (strain JMP134) is capable of growing on both 2,4-dichlorophenoxyacetate (2,4-D) and 3-chlorobenzoate (3-Cba), while Pseudomonas putida carrying plasmid pAC27 (strain AC867) can utilize only 3 Cba as the sole carbon source. The tfdCDEF operon of the pJP4 plasmid and the clcABD operon of plasmid pAC27 each encode enzymes for the degradation of chlorocatechols (Clc), key intermediates in the catabolism of 2,4-D and 3-Cba. Similarities in the nucleotide (nt) sequences of genes tfdC and clcA, encoding pyrocatechases, were reported earlier [Ghosal and You, Mol. Gen. Genet. 211 (1988a) 113-120]. Genes tfdD and clcB, encoding Clc-specific cycloisomerases, have been completely sequenced. The tfdD gene (1107 bp) is slightly smaller than gene clcB (1113 bp). Comparison of the two cycloisomerase-encoding genes reveals that the nt sequences are 63% homologous with 62% homology in the deduced amino acid (aa) sequences of the polypeptides they encode. Genes tfdD and tfdE are contiguous in the tfdCDEF operon, whereas the corresponding genes, clcB and clcD, of the clcABD operon, are known to be separated by a long open reading frame of unknown function. The predicted N-terminal aa sequences of the two hydrolase encoding genes, tfdE and clcD, also show homology. The structural and nt homologies between the two Clc operons, tfdCDEF and clcABD, suggest their relatedness. PMID- 2583529 TI - The bovine and ovine genomes contain multiple sequences homologous to the alpha lactalbumin-encoding gene. AB - Bovine and ovine (pseudo)genes homologous to the alpha-lactalbumin-encoding gene are described. In both cases, sequence analysis reveals homology extending downstream from exon 2. Southern analysis indicates the presence of a family of alpha-lactalbumin-related sequences in the bovine genome. PMID- 2583530 TI - Cloning and sequencing the cDNA encoding pig liver thioltransferase. AB - We report here, the first successful cloning and sequencing of a full-length cDNA gene (TT) encoding the pig liver thioltransferase (TT). The TT cDNA was obtained by screening a commercial (Clonetech) pig liver cDNA library in lambda gt11, using polyclonal antibodies raised in rabbits against pig liver TT. Two positive clones were identified in 3.5 x 10(5) recombinants. For verification, we successfully hybridized three oligodeoxyribonucleotide nucleotide probes, synthesized according to three different regions of the pig liver TT amino acid (aa) sequence, to both of the positive clones. In addition, the size of the TT beta-galactosidase fusion protein, produced by the positive clone, was consistent with the length of the cDNA. The TT cDNA was subcloned into the EcoRI site of M13mp18 replicative form and sequenced by the dideoxy chain-termination method using 35S-labeled nucleotides. The aa sequence deduced from the cDNA sequence is in exact agreement with the previously reported primary aa sequence, except that the N terminus should be N-acetylalanine followed by glutamine, rather than the reverse, as originally interpreted by conventional mass spectrometry fast atom bombardment analysis of the tryptic peptide corresponding to the first 8 aa residues. PMID- 2583531 TI - Lysozyme, a major low-molecular-weight cationic protein of the intervertebral disc, which increases with ageing and degeneration. AB - Lysozyme was demonstrated to increase in content in the human intervertebral disc in a significant age-dependent manner. In young discs (less than 20 years) the levels were 440 U/g wet weight, whereas in older discs (greater than 65 years) the concentration was 3,460 U/g wet weight. These findings contrasted with the hexuronate level (as a marker of proteoglycans) and neutral sugar content of the tissues which decreased with age. The level of lysozyme determined in the disc tissue also correlated with the morphological grade of disc degeneration. PMID- 2583532 TI - Effect of sodium selenite on antioxidative enzymes of banana fruitfly. AB - The median and maximum life spans of Zaprionus paravittiger are 43 and 79 days, respectively, for males and 52 and 91 days for females at 24 +/- 2 degrees C. Sodium selenite (SS), an antioxidant, feeding prolongs the median as well as maximum life span of both the sexes. Antioxidative enzymes, catalase and peroxidase showed greater activity during the developmental stages. Females, at most of the age intervals, exhibited greater enzymatic activities as compared to their age-matched males. Both the sexes showed a statistically significant increase in the baseline activity of these enzymes as consequent upon SS feeding. It is suggested that SS acts by strengthening the antioxidative enzymes, namely catalase and peroxidase. PMID- 2583534 TI - Lymphocyte glutamate dehydrogenase activity in normal aging and neurological diseases. AB - The activity of total and heat-stable glutamate dehydrogenase (GDH) in lymphocytes increased with aging in 40 control subjects (p less than 0.001). The total GDH activity was lower in patients with olivopontocerebellar atrophy (OPCA), motor neuron disease, Parkinson's disease or Alzheimer's disease than in age-matched control subjects, but not in patients with nondegenerative neurological diseases. The decrease in heat-stable GDH activity was observed in patients with OPCA, Parkinson's disease or Alzheimer's disease, but heat-labile GDH was decreased only in patients with OPCA. PMID- 2583533 TI - Plasma 25-hydroxyvitamin D concentration in patients with hip fracture in Hong Kong. AB - The serum concentration of 25-hydroxyvitamin D level and plasma albumin-adjusted calcium, phosphate, and alkaline phosphatase levels were studied in 200 patients with hip fracture (age range 49-93 years) and 427 elderly subjects living in the community (age range 60-90 years). The mean serum 25-hydroxyvitamin D levels in controls were higher than in temperate countries, but the 25-hydroxyvitamin D concentration was significantly lower in the patients than the controls for all sex and age groups. There was little difference in albumin-adjusted calcium and alkaline phosphatase levels, but the phosphate level was higher in the patients than in the controls. None of the patients with a low 25-hydroxyvitamin D level had a blood picture suggestive of osteopathy resulting from vitamin D deficiency or frank osteomalacia. Hip fracture patients with a low 25-hydroxyvitamin D level were much less ambulant and went outdoors much less frequently than hip fracture patients with a normal vitamin D level. A low vitamin D level was a risk factor for hip fracture in Hong Kong Chinese, and may be prevented by frequent outdoor exposure. PMID- 2583535 TI - Use of sensitive thyrotrophin measurements in an elderly population. AB - The investigation of thyroid disease in the elderly is difficult. Conventional tests are influenced by ill health and abnormal concentrations of thyroid binding proteins. To screen for thyroid disease thyroxine (T4), then tri-iodothyronine (T3) or TSH and an index for binding proteins are normally measured, methods which are expensive and time-consuming. TSH immunoradiometric assays (IRMA) offer the potential of a single test assessment of thyroid function in the elderly. This was assessed by comparing the measurement of IRMA-TSH with T4, T3 and the free thyroxine indices in 290 elderly subjects. Concordant results were obtained in 236 subjects. Non-concordant results were seen in 54 subjects. The commonest cause was sick euthyroid syndrome but 4 cases of high T4 and normal TSH were seen with amiodarone therapy. PMID- 2583536 TI - Psychology of aging. AB - Psychology of aging is both part of life-span developmental psychology and gerontology. Courses in this area are becoming a key part of gerontological education curriculum. The development of psychology of aging courses needs to draw on a life-span perspective with its intervention orientation. PMID- 2583537 TI - Social gerontology: an essential part of the "backbone". AB - This paper will discuss some of the major topics which are essential to a core course in Social Gerontology and some suggestions for how best to help students understand these topics. It is assumed that Social Gerontology is an essential part of the "backbone of gerontology." PMID- 2583538 TI - Public policy and aging in the gerontology curriculum: suggestions for a model course. AB - This paper presents suggestions for a model master's level course in public policy and aging. Course content should focus on the historical context of aging policy development, the policy making process, and the legislative history and current content of specific aging policies. Suggestions for teaching resources and class assignments are included. PMID- 2583539 TI - Experiential learning in gerontology: methods for applying concepts and theories to practice. AB - Theories of developmental aging are a crucial component of professional training in gerontology and methods for applying these theories are equally important. Current models are presented which include a variety of opportunities to test theories and develop skills in the gerontology classroom. In addition, the methodology of field studies and consultation are discussed. Various practica models and the instructor's role in organizing and directing them are also presented. PMID- 2583540 TI - Assessment of gerontology certificate program quality: a follow-up study of graduates. AB - A follow-up survey of gerontology certificate program graduates was undertaken to elicit views about quality and impact of their interdisciplinary studies, professional roles, and usefulness of course offerings. Graduates provided recommendations about essential course content and suggestions to assist the university in certificate program development. The data strongly support program objectives and direction. PMID- 2583542 TI - Biology and physiology of development of aging. AB - The presentation of a new language of biology and physiology to undergraduate and graduate students in gerontology is a challenge met with varied approaches in content and form. Major issues in content are presented with reference to encyclopedic and more readable texts and journals. Use of audiovisual, discussion, and written materials are identified. The importance of ongoing evaluation, knowledge and implementation of the most current information, and goals of undergraduate and graduate courses are addressed. PMID- 2583541 TI - An ambulatory geriatric evaluation unit in a family geriatric curriculum. AB - Training in Geriatric Medicine has become increasingly important in the education of family physicians. This paper describes the experience of a community-based Family Medicine residency in developing an ambulatory Geriatric Evaluation Unit (GEU) as part of a comprehensive geriatric curriculum. The experience demonstrates the value of a multidisciplinary team approach, systematic development and integration of additional education activities as effective techniques for training family physicians and ancillary health care providers. PMID- 2583543 TI - Free radicals in medicine. An international symposium. Vienna, November, 1988. PMID- 2583544 TI - Histophotometric quantification of the field effect and the extended field effect of tumors. AB - Histophotometric investigations have been made on samples of human skin. Fresh frozen serial sections were fixed and stained for either reactive protein thiols (PSHr) or total reactive protein sulphur (TRPS) using modifications of the DDD Fast blue B-method. In addition, total protein thiols (PSHt) were stained with the Mercurochromcyanide-method, and proteins were stained using a modified amido black procedure. Significant differences were found between the different tumours investigated and normal tissue, and also between apparently normal tissue adjacent to the tumours and normal tissue from patients without tumour. To reveal such tumour-related changes of apparently normal tissue, termed the field effect of tumours, a double quotient had to be calculated from the PSHr-and TRPS-values determined from both epithelium (epidermis) and connective tissue. In addition, abdominal skin was investigated from patients without tumour and patients with tumours of the female genital tract, liver or breast. With the aid of the double quotient procedure, highly significant differences were found between normal abdominal skin of patients without tumours versus similar samples taken from patients with tumours. The tumour-related changes found with abdominal skin distant from the tumours have been termed the extended field effect of tumours. These general tumour-related changes, independent of the size, state or degree of malignancy of the distant tumour, could be shown to be due to changes in abdominal dermis. PMID- 2583545 TI - Preparation and photosensitizing properties of hematoporphyrin ethers. AB - Hematoporphyrin ethers having acyl or aryl substituents in the 2 and 4 positions of the porphyrin ring have been synthesized, starting from protoporphyrin HBr adduct, and tested for photosensitizing efficiency on cells in vitro and transplanted tumors in mice. In general, they resemble the tumor localizing fraction of hematoporphyrin derivative (Hpd). Cellular uptake and retention runs parallel with the degree of their non-polarity and in vitro sensitizing efficiencies are up to ten times that of Hpd or Photofrin II (P II). They have high quantum yields for inactivation of cells and also relatively low in vivo skin/tumor concentration ratios. PMID- 2583546 TI - 5-Hydroperoxyeicosatetraenoic acid (5-HPETE) enhances the synthesis of 1-O-alkyl 2-sn-acetyl-glycero-3-phosphocholine (PAF) in fMet-Leu-Phe-stimulated HL-60 cells: key role of diacylglycerol (DAG) in activation of protein kinase C (PKC). AB - We investigated the effect of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) on the PAF formation in fMet-Leu-Phe-stimulated HL-60 cells. 5-HPETE was found to enhance the PAF synthesis in fmlp-stimulated cells without causing additional mobilization of intracellular calcium. However, a significant increase in diacylglycerol (DAG) levels due to 5-HPETE was observed, which in turn activated the protein kinase C (PKC). Obviously, PKC is responsible for the activation of phospholipase A2 and the release of lyso-PAF and AA from complex lipid stores. Further, the dose-dependent increase in DAG production in absence of simultaneous increase in total inositol phosphates is indicative of an additional source for DAG besides PIP2. PMID- 2583547 TI - The effects of free radicals on cobalamin and iron. AB - The aim of this communication is to show the means by which free radicals could deleteriously alter the metabolism of cobalamin (vitamin B12) and iron in their attempt to protect the body against neoplasia or inflammation and in doing so, create the anaemia of chronic disease. PMID- 2583548 TI - Role of oxygen-derived free radicals in gastric mucosal injury induced by ischemia or ischemia-reperfusion in rats. AB - Oxygen-derived free radicals have been implicated as possible mediators in the development of tissue injury induced by ischemia and reperfusion. Clamping of the celiac artery in rats reduced the gastric mucosal blood flow to 10% of that measured before the clamping. The area of gastric erosions and thiobarbituric acid (TBA) reactants in gastric mucosa were significantly increased 60 and 90 min after clamping. These changes were inhibited by treatment with SOD and catalase. Thirty and 60 min after reoxygenation. produced by removal of the clamps following 30 min of ischemia, gastric mucosal injury and the increase in TBA reactants were markedly aggravated compared with those induced by ischemia alone. SOD and catalase significantly inhibited these changes. The serum alpha tocopherol/cholesterol ratio, an index of in vivo lipid peroxidation, was significantly decreased after long periods of ischemia (60 and 90 min), or after 30 and 60 min of reperfusion following 30 min of ischemia. These results indicated that active oxygen species and lipid peroxidation may play a role in the pathogenesis of gastric mucosal injury induced by both ischemia alone and ischemia-reperfusion. Although, allopurinol inhibited the formation of gastric mucosal injury and the increase in TBA reactants in gastric mucosa, the depletion of polymorphonuclear leukocytes (PMN) counts induced by an injection of anti-rat PMN antibody did not inhibit these changes. As compared with the hypoxanthine xanthine oxidase system. PMN seem to play a relatively small part in the formation of gastric mucosal injury induced by ischemia-reperfusion. PMID- 2583549 TI - Iron overload and the predisposition of cells to antioxidant consumption and peroxidative damage. AB - We have investigated the effects of iron overload in vivo on the tocopherol levels and the extent of lipid peroxidation in rat liver microsomes and their response to subsequent oxidative stress in vitro. The results demonstrate a direct correlation between consumption of antioxidant defences and the induction and extent of malondialdehyde production in microsomes prepared from iron-loaded rats. The data are consistent with the requirement for iron (II)/iron (III) ratios in lipid peroxidation in control microsomes. PMID- 2583550 TI - Staphylococcal arthritis--effects of superoxide dismutase on infected knee joints of rabbits. AB - The effect of SOD on staphylococcal arthritis has not been successfully evaluated to date. We developed an animal model to investigate the correlation. Using 16 rabbits divided into four groups, we injected two groups with staphylococcus aureus and the other two with NaCl. One group in each was also injected with SOD. The presence of SOD activity in untreated and infected knee joints of rabbits over a period of 72 hours showed no significant difference. TBA-reactive substances (TBARS) measured in joint fluid and plasma did differ in each of the groups, with the highest values found in animals with septic arthritis treated with SOD. This finding corresponded especially with the histological investigation. Joints of infected animals intra-articularly injected with SOD also showed histologically significantly more inflammation, a higher amount of bacteria in the joint cavity, and more distinct joint damage than joints injected only with bacteria. The mechanisms responsible for this SOD effect remain to be determined. PMID- 2583551 TI - Radical formation in the rat small intestine during and following ischemia. AB - Oxidative loading during the reperfusion of the proximal jejunum of rats following a one hour-period of complete ischemia was demonstrated in in vivo experiments by the increases of the GSSG: total glutathione ratio and the concentration of TBA-RS. The pretreatment of the animals with the xanthine oxidoreductase inhibitor allopurinol diminished the accumulation of GSSG and of TBA-RS. It was concluded that the purine nucleotide degradation is an important source of oxygen reduction products in reoxygenated small intestine. The tissue concentrations of nucleotides, nucleosides and nucleobases were measured by an ion-pair reversed-phase HPLC separation. There occurred fast declines of ATP and GTP concentrations during ischaemia leading to temporary increases of nucleoside mono- and diphosphate pools. The hypoxanthine concentration is increased about twentyfold during oxygen deficiency. The ATP and GTP restoration during the reperfusion was accelerated in presence of allopurinol. The shares of the beneficial allopurinol effects are not yet clarified. PMID- 2583552 TI - Alterations in electrolyte and trace-element concentrations during simulated extracorporeal blood circulation. AB - In our studies with simulated extracorporeal blood circulation we observed damaging effects on blood cells, especially under oxygenating conditions. In order to characterize these effects we also analysed electrolyte and trace element concentrations in plasma during and after simulated extracorporeal blood circulation. Highest resorption effects for magnesium and highest desorption effects for calcium, copper and iron are found with oxygen gas flow in the system. Membrane permeability for electrolytes seems to be induced as well. Cellular damage due only to mechanical stress within the perfusion system can be neglected. PMID- 2583553 TI - Cytotoxicity of the hypoxanthine-xanthine oxidase system on V79 cells: comparison of the effects of SOD and CuDIPS. AB - The hypoxanthine - xanthine oxidase system generates an extracellular flux of superoxide anion radical (O2.-) and hydrogen peroxide (H2O2). Catalase but not superoxide dismutase (SOD) protects V79 cells exposed to the hypoxanthine - xanthine oxidase system, showing that H2O2 is the major reactive oxygen species involved in the cytotoxicity of such a system. In contrast to SOD, the lipophilic SOD like compound CuII (diisopropylsalicylate)2 (CuDIPS) exhibits some protection at non cytotoxic concentration. It is also found that methanol partially protects cells exposed to the hypoxanthine-xanthine oxidase system. It appears that in our experimental conditions (temperature, ionic strength and pH) the protective effect afforded by methanol and CuDIPS is due to the inhibition of the xanthine oxidase activity. PMID- 2583554 TI - Effects of free radicals on the fluidity of myocardial membranes. AB - Free radicals, including superoxide anions (O2.-), hydroxyl radical (HO.), and hypohalite radical (OCl.), as well as oxidants such as hydrogen peroxide (H2O2) and hypochlorous acid (HOCl), have been indicated in the pathogenesis of myocardial ischemic and reperfusion injury. In this report, we compared the integrity of the myocardial membrane when exposed to these free radicals/oxidants. Isolated rat heart membrane preparations were exposed to chemically generated free radicals with or without their respective scavengers. Membrane fluidity was monitored by fluorescence polarization using the diphenylhexatriene probe, as well as by electron spin resonance (ESR) spectroscopy using 2,2,6,6-tetramethyl piperidine-n-oxyl as the spin labeling agent. HO., H2O2, and OCl. + HOCl increased the fluorescence polarization (FP) and microviscosity significantly by 1.7-fold, 1.8-fold, and 1.7-fold, respectively, as compared to an only 1.2-fold increase in FP by O2.-. O2.- did not alter the fatty acid profiles of the membrane phospholipids. However, HO. and H2O2 reduced the arachidonic acid contents in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). These radicals also stimulated the lipid peroxidation by several-fold, while that by O2.- was only insignificant. These results suggest that HO. and H2O2 decreased the membrane fluidity and induced lipid peroxidation by releasing the arachidonic acid from PC, PE, and PI. PMID- 2583555 TI - Comparative toxicology of ozone and t-butyl hydroperoxide on isolated rat lung. AB - Comparative studies were undertaken on the effects of ozone and t-butyl hydroperoxide (t-BuOOH) on alkane production, glutathione and lactate dehydrogenase (LDH) release from isolated rat lungs. Specifically, ethane and pentane production, as well as glutathione and LDH release were simultaneously determined at different time intervals from the isolated lung preparation in the absence and presence of toxic concentrations of ozone or t-BuOOH. When compared to control conditions, both toxic agents produced a marked decrease in the dry weight to wet weight ratios, reflecting the development of acute pulmonary edema. These toxic agents also caused a marked increase in the efflux of glutathione into the effluent. A much higher glutathione efflux into the effluent was observed during t-BuOOH perfusion in comparison to ozone exposure. In parallel with the enhancement of glutathione release a significant increase in ethane production was also observed during t-BuOOH perfusion. However, the production of either alkane by ozone inhalation was not significantly different from that in the control conditions. Unlike glutathione release, there was no marked increase of LDH release into the effluent following exposure to t-BuOOH or ozone. This suggests that the observed increase in glutathione release caused by t-BuOOH or ozone treatment was not associated with non-specific destruction of cell membrane integrity. PMID- 2583557 TI - The British Society of Gastroenterology. 1989 annual general meeting. Dublin, 27 29 September 1989. PMID- 2583556 TI - Binding of iron to human red blood cell membranes. AB - The binding of Fe3+ to red cell membranes was studied in a system in which lipid peroxidation was proportional to Fe3+ concentration. Binding of Fe3+ was evaluated by labeling with 59FeCl3 and measurement of NMR water-proton relaxation times. Labeling with 59Fe showed that 95% of the Fe3+ was membrane bound at 100 microM FeCl3 in a 1.5 mg protein/ml membrane suspension. Both spin-lattice (T1) and spin-spin (T2) relaxation times decreased with increasing Fe3+ concentration. Addition of red cell membrane suspensions largely prevents the Fe3+ effect on relaxation times. Charge transfer to Fe3+ may occur at the membrane binding site with resultant decrease in the Fe3+ effect on water-proton relaxation times. These studies support the hypothesis that Fe3+ binds to the membrane and generates free radicals at the binding site. PMID- 2583558 TI - Is yield pressure at the cardia increased by effective fundoplication? AB - Yield pressure at the cardia was measured before and after fundoplication in 10 patients; five had a Nissen fundoplication and five a Belsey mark IV procedure. Surgery was considered successful if oesophagitis healed or if 24 hour pH monitoring returned to normal. There was a marked rise in yield pressure in all eight patients with a successful operation. Yield pressure remained low in two patients in whom oesophagitis persisted. PMID- 2583559 TI - Effect of cimetidine and ranitidine on drug induced damage to gastric epithelial cell monolayers in vitro. AB - The effect of the H2 blockers cimetidine and ranitidine on drug induced damage to gastric cell monolayers has been evaluated in conditions independent of systemic factors and their anti-acid properties. Monolayers of mucous cells from a human cell line MKN 28, obtained from a human gastric adenocarcinoma, have been studied. Cell damage has been assessed qualitatively by trypan blue dye exclusion test and quantitatively by 51Cr release assay. Cimetidine and ranitidine significantly protected cultured cells against damage induced by sodium taurocholate decreasing taurocholate induced 51Cr release by 36% (p less than 0.001) and 28% (p less than 0.01), respectively. Cimetidine was also protective in concentrations lower than ranitidine. This protection was not prevented by the prostaglandin synthesis inhibitor indomethacin nor by the sulph-hydryl blocker N ethylmaleimide. Incubation with cimetidine and ranitidine did not increase the production of PGE2 by cultured cells nor did it affect the cellular level of sulph-hydryl compounds. Cimetidine and ranitidine did not afford protection against damage induced by indomethacin and ethanol. Cimetidine in a concentration of 10 4M increased ethanol induced damage significantly. In conclusion (1) cimetidine and ranitidine protect gastric cells against taurocholate induced damage in vitro, independently of their anti-acid effect; (2) this protection is not mediated by prostaglandin E2 or sulph-hydryl compounds; (3) cimetidine and ranitidine do not protect gastric cells against damage induced by indomethacin and ethanol. PMID- 2583560 TI - Profound spatial clustering of simultaneous peptic ulcers. AB - In an endoscopic study of 90 consecutive patients with more than one peptic ulcer, the ulcers in an individual were profoundly spatially clustered. Clustering of ulcer locations was shown using a non-parametric test of clustering (Kruskal-Wallis statistic with 89 degrees of freedom = 151.31, probability of observing this extreme statistic with no clustering less than 0.0005) and a parametric test of clustering (F test statistic with 89 and 124 degrees of freedom = 5.41, probability of observing this extreme statistic with no clustering less than 0.0005). Patients having their largest ulcer in any given region had a much greater likelihood than other patients of having other ulcers in that same site. For example, the 26 patients with their largest ulcer in the proximal duodenal bulb had 20 of 33, or 61% (9) (standard error), of their other ulcers in the proximal duodenal bulb. In contrast, the 18 patients with their largest ulcer in the proximal stomach had four of 23, or 17% (8), of their other ulcers in the proximal duodenal bulb. Of the 59 patients who had two simultaneous ulcers, 28 patients had adjacent ulcers (distance between ulcers less than 4% of the distance from the gastric cardia to the apex of the duodenal bulb). These findings suggest that local factors may be important in the pathogenesis of simultaneous peptic ulcers, including infection caused by Campylobacter pylori or other microorganisms, ischaemia and mucosal barrier disruption. PMID- 2583561 TI - Patterns of colonisation of Campylobacter pylori in the oesophagus, stomach and duodenum. AB - Thirty five subjects underwent upper gastrointestinal endoscopy and multiple biopsy (30 patients, five normal subjects). A total of 11 biopsies per subject from four sites (oesophagus (three), gastric body (two), antrum (three), duodenum (three] were examined for inflammation and the presence of Campylobacter pylori and using standard methods of culture and by light (LM) and electron microscopy (EM). The organism was cultured from oesophageal biopsies in eight of 30 (27%) patients but could not be identified at this site by LM or EM. There was evidence of oesophageal inflammation in 20 patients which was associated with the local finding of C pylori in five (25%) including two of seven (29%) with Barrett's mucosa. Antral C pylori was present in 22 of 23 (96%) patients with chronic active gastritis. The organism was found in the antrum and oesophagus in four of 22 patients (18%), in the antrum and duodenum in four of 22 patients (18%) and in all three sites in a further two of 22 patients (9%). Antral C pylori was found in five of six patients with peptic ulceration. C pylori was cultured from the duodenum in six patients with confirmation by LN and EM in three, but only on areas of gastric metaplasia. The organism was not found in the normal group. This study indicates that C pylori may be irregularly isolated from the oesophagus and duodenum in patients with antral C pylori and chronic active gastritis. The role of C pylori in the oesophagus is most likely that of a commensal or contaminant. PMID- 2583562 TI - Glycoprotein synthesis and secretion by cultured small intestinal mucosa in coeliac disease. AB - Glycoprotein biosynthesis by jejunal mucosa was examined during culture in vitro in 26 patients with coeliac disease and 19 controls. The incorporation rates of tritiated glucosamine into tissue and secreted glycoproteins were determined using established techniques. The total glucosamine incorporation in untreated coeliac patients was significantly greater than that of histologically normal mucosa (p less than 0.001) and jejunal tissue from patients with treated coeliac disease (p less than 0.01). Enhanced secretion of in vitro labelled glycoproteins was observed in untreated coeliac patients. The total incorporation of tritiated glucosamine in intestinal tissues was correlated with goblet cell numbers. These results indicate that quantitative changes in glycoprotein synthesis and secretion occur in coeliac disease. PMID- 2583563 TI - Near infrared spectrometry for faecal fat measurement: comparison with conventional gravimetric and titrimetric methods. AB - This investigation was aimed at comparing a new method for measuring faecal fat excretion, carried out with a semi-automated instrument by using near infrared analysis (NIRA), with the traditional titrimetric (Van de Kamer) and gravimetric (Sobel) methods. Near infrared analysis faecal fat was assayed on the three day stool collection from 118 patients (68 chronic pancreatitis, 19 organic diseases of the gastrointestinal tract, 19 alcoholic liver disease, 12 functional gastrointestinal disorders). A strict linear correlation was found between NIRA and both the titrimetric (r = 0.928, p less than 0.0001) and the gravimetric (r = 0.971, p less than 0.0001) methods. On homogenised faeces, a mean coefficient of variation of 2.1 (SD 1.71)% was found. Before homogenisation (where a mean coefficient of variation of 7% was found) accurate results were obtained when the mean of five measurements was considered. In conclusion, the assay of faecal fat excretion by the near infrared reflessometry appears a simple, rapid and reliable method for measuring steatorrhoea. PMID- 2583564 TI - Significance of venous and lymphatic invasion in malignant polyps of the colon and rectum. AB - Three hundred and sixty seven neoplastic colorectal polyps removed at endoscopy of which 34 were complicated by invasive carcinoma, were reviewed clinically and histologically to assess the prevalence and clinical significance of venous and or lymphatic invasion. Traditional stains for histological assessment were supplemented by immunohistochemical methods. Venous and or lymphatic invasion was present in six cases (17.6%), with a statistically significant association with recurrent carcinoma or Dukes's C carcinoma in polyps otherwise regarded as completely excised. The presence or absence of venous and or lymphatic invasion in malignant polyps should be documented as if present, further treatment is indicated. A combination of haematoxylin and eosin and elastic-van Gieson stains will usually identify the presence of vascular invasion. Where a discrepancy arises, however, additional immunohistochemical stains may be of value. PMID- 2583566 TI - Effects of non-shunting operation on azygos venous blood flow in cirrhotic patients. AB - Azygos venous blood flow and other haemodynamic parameters were measured in 14 cirrhotic patients to investigate the effects of a non-shunting operation, oesophageal transection with paraoesophagogastric devascularisation. Azygos venous blood flow measured by the local continuous thermal dilution method was significantly reduced by 13.8% after the operation (428 (41) v 369 (33) ml/min). Hepatic venous pressure gradient (HVPG) was also significantly decreased from 14.5 (0.8) to 12.8 (0.7) mmHg (-11.8%). Cardiac output and routine liver tests did not change remarkably postoperatively. In this haemodynamic study before and after non-shunting operation, moderate but significant decreases were seen in azygos venous blood flow and portal pressure (HVPG), without substantial changes in systemic circulation. This suggests that blood flow through the portosystemic collaterals other than oesophageal varices may be decreased but still adequate after the operation. Well preserved portosystemic collaterals without oesophageal varices are thus considered an optimally balanced state after non-shunting operation. PMID- 2583565 TI - Plasma leucine enkephalin is increased in liver disease. AB - Plasma methionine enkephalin is increased in liver disease and may contribute to some of the clinical manifestations of hepatic failure. To determine if another 'small' opioid peptide is increased in the plasma of patients with liver disease, leucine enkephalin was measured by radioimmunoassay. Its plasma concentration was raised approximately five-fold in patients with acute liver disease (median 1490 pmol/l, range 830-2420) and three-fold in patients with cirrhosis with ascites (960 pmol/l, 470-2900), compared with disease controls (325 pmol/l, 180-740) and healthy controls (305 pmol/l, 180-560). The increase in plasma leucine enkephalin was proportional to the degree of liver damage, as judged in the patients with acute liver disease by its correlation with the prothrombin time (r = 0.691, p less than 0.01) and alanine aminotransferase (r = 0.502, p less than 0.05), and in the patients with cirrhosis by its negative correlation with the plasma albumin (r = -0.743, p less than 0.001). It is unclear whether the raised plasma leucine enkephalin in liver disease is a consequence of diminished hepatic inactivation, increased secretion from sympathetic nerves and adrenal glands, or both. PMID- 2583568 TI - Extracorporeal shock wave lithotripsy of pancreatic stones. AB - Extracorporeal shock wave lithotripsy of pancreatic stones was performed in eight patients with chronic pancreatitis and a dilated duct system harbouring stones 5 to 20 mm (means 10 (SD) 5 mm) in diameter. After endoscopic sphincterotomy of the pancreatic orifice the stones were disintegrated by shock waves under fluoroscopic control using a kidney lithotripter (Dornier HM3). The procedure was well tolerated by all but one patient, who had a mild pancreatitic attack immediately after lithotripsy. Clearance of the pancreatic duct systems from the larger stones was achieved in seven of eight patients. Half of the patients showed no improvement in the intensity and frequency of pain. The other patients had a marked amelioration of symptoms, however, both immediately and during a mean follow up interval of 11 (eight) months. A selective combined approach by endoscopy and extracorporeal shock wave lithotripsy for the treatment of pancreatic stones seems promising. PMID- 2583567 TI - Comparison of albendazole, mebendazole and praziquantel chemotherapy of Echinococcus multilocularis in a gerbil model. AB - The efficacy of albendazole (50 mg/kg/d), mebendazole (50 mg/kg/d) and praziquantel (500 mg/kg/d) against established intraperitoneal infections of Echinococcus multilocularis in gerbils was compared by monitoring parasite weight and making ultrastructural observations on treated and untreated material. Praziquantel was the most active protoscolicidal agent, reducing protoscolex viability to less than 2%, although it did not inhibit cyst growth. Albendazole was the most effective agent in reducing cyst growth and was, when compared with other regimes significantly more effective than mebendazole (p less than 0.05), praziquantel (p less than 0.01) or untreated controls (p less than 0.01). PMID- 2583569 TI - Peculiar acute toxic colitis after ingestion of colocynth: a clinicopathological study of three cases. AB - We report three examples of toxic acute colitis which occurred after ingestion of colocynth (Citrullus colocynthis) for ritual purposes. The prominent clinical feature was dysenteric diarrhoea; colonoscopic changes included congestion and hyperaemia of the mucosa with abundant exudates but no ulceration or pseudopolyp formation. A causal relationship between colonic injury and the intake of colocynth was supported by the following features: (1) the pharmacology of the colocynth extract ingested; (2) the temporal relationship between colocynth intake and clinical onset (eight to 12 h); (3) the rapid recovery within three to six days, with normal endoscopy at day 14; (4) the absence of other possible causes for the observed patterns, except in one case, in which a concomitant intestinal infection with Clostridium perfringens Type A was discovered; (5) the specific pathological features. Colonic biopsies taken 27, 44, and 72 h after colocynth intake showed: erosions with fibrino-purulent exudate, early fibrosis of the lamina propria, hyaline thickening of the superficial epithelial basal membrane. These pathological features completely disappeared within 14 days in all three cases. PMID- 2583570 TI - Development of chronic hepatocerebral degeneration eight years after a distal splenorenal (Warren) shunt. AB - It is well known that chronic encephalopathy may be a major complication after the establishment of a surgical portal caval shunt for an episode of variceal haemorrhage. In an effort to minimise this problem Warren and colleagues developed the distal splenorenal shunt where the portal and mesenteric blood flow to the liver was left intact. It is now recognised, however, that the longterm incidence of encephalopathy may be no different with this type of shunt compared with conventional surgical portal systemic shunts. Acquired chronic hepatocerebral degeneration has not been reported after such a selective shunt. A patient with primary biliary cirrhosis is reported who developed the clinical features of this syndrome eight years after a successful distal splenorenal shunt. PMID- 2583571 TI - Fatal variceal haemorrhage after paracetamol overdose. AB - A patient is described where oesophageal varices developed and bled 13 days after a paracetamol overdose. The bleeding was unresponsive to medical management and proved fatal. There was no evidence that the patient had pre-existing liver disease. At necropsy the liver showed severe acute parenchymal necrosis but chronic lesions were absent. The portal vein and hepatic veins were patent. PMID- 2583572 TI - Nodular regenerative hyperplasia of the liver, CREST syndrome and primary biliary cirrhosis: an overlap syndrome? AB - Nodular regenerative hyperplasia of the liver (NRHL) has been found in association with collagen vascular diseases, after drug therapy, with autoimmune disease, and with a variety of haematological disorders. The association of NRHL with the syndrome of Calcinosis cutis, Raynaud's phenomenon, oesophageal dysfunction, sclerodactyly and telangiectasia (CREST syndrome) has only been reported on two previous occasions. The liver disease usually associated with CREST syndrome is primary biliary cirrhosis (PBC) and recently nodular hyperplasia of the liver has been reported in patients with early stage PBC. We present a case of NRHL with CREST syndrome and serological and biochemical features of PBC, a newly recognised overlap syndrome. PMID- 2583573 TI - Comparison of gastric body and antral pH. PMID- 2583574 TI - Piezoelectric shockwave fragmentation of biliary calculi. PMID- 2583576 TI - Processing gastric pH measurements. PMID- 2583575 TI - Chronic colitis after Aeromonas infection. PMID- 2583577 TI - Whys and whats of wandering. PMID- 2583578 TI - Shedding light on nocturia. PMID- 2583579 TI - The next step. PMID- 2583580 TI - Health in the sandwich generation. PMID- 2583581 TI - What do you mean? PMID- 2583582 TI - Nursing diagnoses: not for individuals only. PMID- 2583583 TI - Community of caring. PMID- 2583584 TI - Not another lecture! PMID- 2583585 TI - [Inguinal lymphoma with lymphedema of the leg as the leading symptom of tubal cancer]. PMID- 2583586 TI - [Breast cancer: a diagnostic or therapeutic problem?]. PMID- 2583587 TI - [Breast-saving therapy of primary breast cancer. Results of the Zurich University Gynecologic Clinic]. PMID- 2583588 TI - [Gynecologic surgery in the elderly patient]. PMID- 2583589 TI - [Changes in urodynamic parameters following cystourethropexy]. PMID- 2583590 TI - [Can progress in obstetrics be measured?]. PMID- 2583591 TI - [The university hospital and critical care hospital: an interactive educational system]. PMID- 2583592 TI - [The gynecology clinic in the era of electronic data processing]. PMID- 2583593 TI - [35 years of gynecology--retrospect and prospects]. PMID- 2583594 TI - IgE levels in normal human sera and IgG preparations. AB - Serum IgE levels were determined in 318 Hungarian blood donors by PRIST technique. Age-dependent decrease of IgE and higher values in males than in females were found. Commercial IgG preparations contained variable amounts of IgE related to the procedures for purification. The normal IgE level in healthy Hungarian adults were compared to the reported normal values of other countries. PMID- 2583595 TI - Relationship between adenosine deaminase activity (ADA) and inosinemonophosphate (IMP) accumulation in fresh erythrocytes incubated with adenosine and dipyridamole. AB - Fresh human erythrocytes were incubated in two media: a) adenosine (10 mM), pyruvate (10 mM), phosphate (50 mM) (APP medium); b) APP medium enriched with 100 mumol/l dipyridamole (APPD) medium. The amount of IMP in fresh erythrocytes was 0.18 +/- 0.09 mumol/g Hb, after incubation in APP medium it was 1.52 +/- 0.78 mumol/g Hb, and after incubation in APP medium it was 1.52 +/- 0.78 mumol/g Hb, and after incubation in APPD the amount was 5.28 +/- 0.94 mumol/g Hb. ADA activity was measured simultaneously. The mean activity (+/- SD) of ADA fresh red cells was 1.29 +/- 0.36 U/g Hb, after 2 h incubation in APP medium it was 1.71 +/ 0.38 U/g Hb, and after 2 h incubation in APPD medium an activity of 2.68 +/- 0.95 U/g Hb was found. A highly significant correlation between the accumulation of IMP and the activity of ADA in fresh erythrocytes (r = 0.93; p = less than 0.001) and in erythrocytes incubated in APPD medium (r = 0.97; p = less than 0.001) was found. PMID- 2583596 TI - Clinical features of hepatic sequestration in sickle cell anaemia. AB - Episodes of hepatic sequestration were seen in four patients with sickle cell anaemia (SCA). One case presented a severe and fatal sequestration crisis whereas the others showed mild episodes associated with less striking haematological and clinical changes. These clinical pictures are similar to those seen in the splenic sequestration crises of children with SCA. Different causes of liver enlargement in SCA suggest that the clinical spectrum representing intrahepatic trapping of blood could range from the acute sequestration crisis to chronic sequestration events which very probably should play any role in the pathogenesis of the hepatomegaly frequently found in these patients. PMID- 2583597 TI - Alpha-thalassemia changes the cell density profile in sickle cell anaemia. AB - Several factors are implied in the haematological and clinical picture of sickle cell anaemia. Attention has been focused on the concomitant presence of -alpha thalassemia and high levels of HbF, but contradictory results have been reported in different populations. We compared the blood cell density profile, obtained by the phtalate esther method, of normal subjects with those of patients with sickle cell anaemia - with or without heterozygous alpha-thalassemia. We found that the density profile of both groups of patients differs from normal subjects, and that a difference can also be demonstrated between normal alpha genotype patients with sickle cell anaemia and patients with heterozygous alpha-thalassemia. These results are in agreement with the findings obtained in other countries in which a gene from Caucasian to African populations have been demonstrated, and are different from the results obtained in populations of more pure African ancestry. It can be suggested, therefore, that these data, in addition with findings of other authors in different geographical areas, support the hypothesis that the genetic make up plays an important role in the haematologic and clinical picture of sickle cell anaemia. PMID- 2583598 TI - Preparation of leukocyte-poor platelet concentrates for transfusion by filtration through a new cellulose acetate filter. AB - The preparation of leukocyte-poor platelet concentrates using a new cellulose acetate filter was evaluated. The platelet loss was 9% when freshly prepared platelet concentrates were filtered. The platelet loss was more variable and about 16% (p less than 0.05) when 5 day old platelets were filtered. The leukocyte removal was not influenced by storage time. The mean absolute number of leukocytes was about 1 x 10(7) and 3 x 10(7) for freshly prepared or 5 day old platelet concentrates, respectively (p less than 0.05). The leukocyte-poor platelet concentrate prepared by the described filtration procedure may be used as a blood component in transfusion therapy to prevent or delay platelet alloimmunization. PMID- 2583599 TI - Functional determination of C1 esterase inhibitor in fractions derived from plasma. AB - A traditional esterolytic assay, a commercial chromogenic assay and an in-house chromogenic assay were compared for suitability in estimating C 1 esterase inhibitor (C 1 INH) activity in plasma and fractions obtained during preparation of a clinical concentrate of C 1 INH. The esterolytic and both of the chromogenic assays showed similar C 1 INH activity in unfractionated plasma samples. However, the esterolytic assay was significantly influenced by the buffer pH and concentration in fractionated plasma samples, and this often resulted in a significant overestimation of C 1 INH in some fractions. Similarly, the commercial C 1 INH assay kit did not always reliably estimate C 1 INH activity in fractions derived from plasma. A modified in-house functional assay was found to be more reliable in measuring C 1 INH in fractionated plasma samples. There was a good correlation between this activity assay and immunological assay estimates of C 1 INH in fractions derived from plasma. PMID- 2583600 TI - Central nervous system acute promyelocytic leukaemia: a report of three cases. AB - Authors report 3 cases of acute promyelocytic leukaemia, in which the central nervous system was involved in the first period of relapse. The clinical features of these patients are discussed. Authors conclude that central nervous system involvement in acute promyelocytic leukaemia must be considered a very bad prognostic sign, because in these cases a rapidly progressive course may be expected. PMID- 2583601 TI - [Platelet-modified LDL: uptake and metabolism in macrophages]. AB - Mouse peritoneal macrophages accumulate large amounts of cholesterol ester when incubated with chemically or biologically modified lipoproteins. Incubation of LDL with platelet secretory products for 2 hours at 37 degrees C decreases its protein and cholesterol content. Subsequently this modified LDL, named PCM-LDL, enhances in-vitro platelet aggregation. When it is incubated with cultures of macrophages, cholesterol accumulates in the cells and esterification is increased. PCM-LDL is taken up by macrophages via a receptor-mediated mechanism, independent of the scavenger receptor for acetyl-LDL. Its degradation in lysosomes is required for stimulation of cholesterol ester synthesis. PMID- 2583602 TI - [Evaluation of VIIIth nerve disorders in learning-disabled children]. AB - Recent research indicates that a subclinical VIIIth nerve defect can be a major contributing factor to, if not a cause of learning disabilities. A battery of tests developed for evaluation of VIIIth nerve function is presented. These tests include assessment of vestibular function and evaluation of auditory figure ground abilities. 70 primary school children diagnosed as learning-disabled by child study teams were tested using this battery. 94% had abnormal findings in the electronystagmographic test and 22% in the auditory figure ground test. This battery of tests can detect subclinical defects in learning-disabled children which can be alleviated by a combination of proper medical treatment and an appropriate educational plan. PMID- 2583603 TI - [Delay in the diagnosis of malignant melanoma]. AB - We investigated delay in the diagnosis of malignant melanoma using the files of 180 patients diagnosed from January 1979 through October 1980, and interviewed 103 of the patients. 62% of the patients sought medical help more than 6 weeks after the appearance of symptoms, and the median delay was 6 months. There was no correlation between delay in diagnosis and sex or country of origin. Those in whom the primary tumor had bled were diagnosed earlier than those with other initial symptoms. Those with some knowledge of the signs of skin cancer did not seek medical care earlier than those without. The most frequent reasons for delay in diagnosis were that patients thought the lesions were insignificant or that they would heal without medical intervention. The first physician most patients consulted was their family physician or a dermatologist. Most family physicians (85%) immediately referred the patient to a dermatologist or plastic surgeon. 30% of the dermatologists did not refer the patient immediately for surgery, thus delaying diagnosis and treatment. Education of the public, and of physicians as well, is needed in the prevention and early detection of malignant melanoma. PMID- 2583605 TI - [Traumatic fracture of the corpus cavernosum with urethral rupture]. AB - Traumatic fracture of the corpus cavernosum with urethral rupture occurs rarely, mostly during intercourse. About 200 cases have been published. Some reports favor conservative treatment, but lately it has been shown that this results in longer hospitalization and to late complications in 29%. Cavernography should be used in the equivocal cases without hematuria or signs of fracture. We present a case of fracture of the corpus cavernosum and tear in the urethra. Treatment consisted of surgical repair of the tunica albuginea and stenting of the urethra. Long term results were excellent. PMID- 2583604 TI - [Is Solcoderm suitable for treating malignant skin tumors?]. AB - Solcoderm, a liquid preparation developed in the USSR, is recommended for topical treatment of benign and malignant skin tumors. We present 5 out of 25 patients treated in our department over the past 2 years who had been treated with Solcoderm for malignant skin tumors. The preparation appeared to have affected only the superficial layers of the tumor and had not penetrated in depth. Cellular remnants tended to spread far beyond the confines of the original tumor and seemed to become much more aggressive. To be effective, the technique of applying the drug would have to be much more complicated than originally specified. Both the functional and esthetic results are much worse than expected. PMID- 2583606 TI - [Traumatic myopia due to ciliary body detachment]. AB - A 20-year-old man developed myopia immediately after blunt trauma to the eye. The main finding was a shallow anterior chamber. Ultrasonography revealed anterior displacement of the iris lens diaphragm without change in lens thickness or axial length of the eye. After 1 week intraocular pressure decreased to a very low level, and edema of the optic disc and macula developed. Since hypotony and shallowness of the anterior chamber persisted for many months, we assume the cause to be detachment of the ciliary body. This is an uncommon mechanism for traumatic myopia, spasm of the ciliary body being more common. PMID- 2583607 TI - [External fixation for open fractures of the femur]. AB - 32 cases of severe open fractures of the femur were treated by external fixation in 1 lateral plane with either the Wagner apparatus or the A.O. tubular system. 2/3 of the cases were war injuries and 1/3 were due to traffic accidents. In 1 case the broken limb was severely burned. In half the cases external fixation was changed for P.O.P. or internal fixation because of pin tract infection or delayed union. There were no non-unions or amputations, but 1 case had chronic post traumatic osteomyelitis. We conclude that the method of choice for 3rd degree open fractures of the femur is external fixation. In the case of severe multitrauma and complex wounds with vascular injury or burns, external fixation is mandatory. PMID- 2583608 TI - [Quality control and quality assurance in medicine]. PMID- 2583609 TI - [Revised criteria for rheumatoid arthritis]. PMID- 2583610 TI - A second finding of Linognathoides laeviusculus (Grube) (Anoplura) in Rumania. PMID- 2583611 TI - The pathogenicity of Cryptosporidium parvum Tyzzer, 1912 and C. Baileyi Current, Upton et Haynes, 1986 for chickens. AB - Clinical symptoms and pathological-morphological changes in the respiratory tract of chickens inoculated with Cryptosporidium parvum were described for the first time and compared with those induced by Cryptosporidium baileyi. Intratracheal inoculation with these two species caused symptoms of a respiratory tract disease in all chicken, but a disease of the digestive tract or death did not occur in any case. Pathological and morphological changes were observed only in the respiratory system and were characterized by petechiae in the mucous of larynx, trachea, primary bronchi and in the wall of air sacs in chickens infected with C. parvum, or by diffuse hyperaemia of respiratory tract mucosa in chickens infected with C. baileyi. The pathological-histological changes, which were characterized by affections of various degrees in epithelial cells, mucous glands, and lamina propria mucosae, were more pronounced in the chickens infected with C. parvum. PMID- 2583612 TI - An unusual localization of developmental stages of Cryptosporidium parvum Tyzzer, 1912 in the cells of small intestine of a gnotobiotic piglet. AB - In a gnotobiotic piglet infected with 50.10(6) oocysts of Cryptosporidium parvum, developmental stages of the parasite were found in the duodenum, anterior jejunum and middle jejunum on the first day post infection (1 DPI). During the studies of the ultrastructure, trophozoites and meronts of C. parvum were encountered in the microvillous zone of enterocytes, and the outer membrane of parasites was a continuation of the membrane of microvilli. Unusual was the attachment of C. parvum trophozoite on the opening of a goblet cell, as well as a meront localized in the cytoplasm in the enterocyte of anterior jejunum. These findings show that C. parvum is very adaptive and capable of developing in a still undescribed location. PMID- 2583613 TI - Ultrastructure of the tail of Echinostoma revolutum cercaria. AB - The ultrastructure of the tail fins and muscles of Echinostoma revolutum cercaria is described. The longitudinal muscles consist of a primitive type of transversely striated muscle fibres with a well-developed sarcoplasmic reticulum in the Z-band. The fins are formed by a longitudinal tegument fold containing the same components as the remaining part of the tail tegument. The difference between the body and tail tegument is discussed. PMID- 2583614 TI - Some trematodes of freshwater fishes from North Vietnam with a list of recorded endohelminths by fish hosts. AB - The present paper comprises a systematic survey of trematodes collected from 12 species of freshwater fishes from North Vietnam (the Red River near Hanoi). Altogether 16 trematode species (14 adults and 2 juvenile forms) have been recorded. These include: Amurotrema dombrowskajae, Platycladorchis microacetabularis, P. macroacetabularis, Neocladorchis multilobularis, Carassotrema koreanum, Azygia hwangtsiyui, Phyllodistomum clariasi, Phyllodistomum sp., Orientocreadium batrachoides, Masenia collata, Bucephalopsis ozakii, Dollfustrema bagarii sp. n., Prosorhynchus vietnamensis sp. n., Prosorhynchus sp. juv., Metadena bagarii sp. n., and Isoparorchis hypselobagri juv. Except for the first four named species, all the trematodes are briefly described and illustrated and some problems concerning their taxonomy and geographical distribution are discussed. D. bagarii sp. n. from Bagarius bagarius (catfish) is characterized mainly by location of the mouth opening in anterior half of body, extension of the uterus anteriorly not surpassing vitellaria, number of spines (about 60) on the rhynchus, and by other features. Characteristic features of P. vietnamensis sp. n. (host B. bagarius) are the structure and shape of the rhynchus, equatorial situation of vitellaria, postequatorial distribution of gonads and mouth opening, extension of the uterus, and body measurements, whereas those of M. bagarii sp. n. (host B. bagarius) include the shape (spherical) of the ovary, extent of caeca (slightly surpassing testes) and body measurements. Carassotrema ginezinskajae Kulakova et Ha Ky, 1976 is considered a junior synonym of C. koreanum Park, 1938. Eight species have not yet been reported from Vietnam. The findings include several new host records. PMID- 2583615 TI - Systematic status of Philometra acipenseris (Del Lupo, 1898) (Nematoda). PMID- 2583617 TI - Population variability of some quantitative characters in Argas polonicus larvae (Acarina: Argasidae). AB - The nature of variability of quantitative morphometrical characters was studied in larvae of two local populations of Argas (Argas) polonicus Siuda, Hoogstraal, Clifford et Wassef, 1979 collected in Czechoslovakia and Poland. Statistically significant differences in five quantitative characters studied, in which the larvae of both wild populations differed from one another, disappeared during three generations of laboratory rearing. The variability of these characters was lower in laboratory populations than in field collected ticks. The results of hybridization experiments and analysis of variability of larvae of individual populations and parental pairs suggest that rather adaptive than genetic variation is involved. The genetic component of the variation is inferior and is expressed probably by dominant relations between alleles of the same locus, or by different types of non-allelic interactions. PMID- 2583616 TI - Chaetotaxy of cercariae of Opisthioglyphe ranae (Frolich, 1791) (Trematoda: Plagiorchidae). AB - A detailed observation of the sensory apparatus of Opisthioglyphe ranae (Frolich, 1791) cercariae was carried out. The species was determined on the basis of an experimental study of the life cycle and morphology of sporocysts, cercariae, metacercariae, and adults. In contrast to other species of the family Plagiorchidae, no papillae were present in the positions CId1, CId2, CII0, CII3 and CII4. Papillae with markedly ventral situation on the postacetabular zone were found very rarely. Some of the cercariae possessed ventral papillae variously distributed in the preacetabular zone. A comparative analysis of the chaetotaxy revealed that the cercaria studied by us was very similar to Cercaria 4 of Richard, 1971, with the exception of the number of acetabular papillae and some groups of ventral papillae. Compared to the cercaria of O. ranae studied by Dobrovolskiy (1965). AID papillae and a part of ventral papillae were distributed differently. The chaetotaxy was identical with that of experimentally obtained cercariae of O. ranae from L. stagnalis and of cercariae of the same species obtained from Bulgaria. PMID- 2583618 TI - Occurrence and localization of Cryptosporidium sp. in spontaneously infected pheasants (Phasianus colchicus L.). PMID- 2583620 TI - [Sequelae of unsecured elastic bands (the status after 7 years)]. AB - The use of elastic bands without an adequate appliance mechanism to close a diastema represents a professional error on behalf of the dentist. Two case reports are presented showing both the consequences of such malpractice and the successful periodontal and orthodontic treatment over a period of seven years. The reasons for this successful treatment are discussed as well as points of special interest. PMID- 2583619 TI - [Changes in clinical crown length during multiband treatment]. AB - The clinical crown lengths of the incisors and first molars of 50 adolescents were measured on dental casts prior to and five to seven months following end of treatment and the differences were recorded. The patients were treated with fixed appliances for an average of 23 months. In addition, initial crown lengths were compared to those of ten children who were four years younger on average. Treatment time and objectives were recorded. Statistically significant differences were determined by means of the t-test. In order to test for correlations between treatment objectives, duration of treatment and change in clinical crown length, correlation analysis was used. The results were: clinical crown length increases physiologically from ten to 14 years of age by about 0.175 mm per year. During fixed appliance therapy in adolescents, the clinical crown length increases. This is accelerated when employing extrusive mechanics, whereas intrusive mechanics reduce this tendency. There is no evidence to suggest that the process is accelerated by the type of appliance. PMID- 2583621 TI - [Physiologic sucking performance and the shape of the oral cavity in infants and young children with respect to the design of nipples for nursing bottles and pacifiers]. AB - Empirical data for functional measurements of the infant oral cavity under stimulated sucking conditions are presented. The data may serve as a basis for the design of nourishing and nipple-shaped pacifiers. Casts of the oral cavity during sucking show a sagittal flattening. The length of the nipple-head influences sucking capacity. PMID- 2583623 TI - [The vertical position and axial inclination of the wisdom teeth. An x-ray study]. AB - In a roentgenographic study we considered the question as to whether the vertical position and inclination of third molars is influenced by orthodontic treatment. Normal inclination and correct vertical relationship of the third molars to the occlusal plane was found more frequently in those patients who received orthodontic treatment - for space closure following extraction or agenesis. There is less likelihood of impacted/displaced third molars in cases where extractions have been carried out as posteriorly in the arch as possible and the resulting space (including space from congenitally absent teeth) has been closed. In Angle class II malocclusions, the maxillary third molar erupted more often into a good position, whereas in the class III malocclusions the mandibular third molars were more reliable. PMID- 2583622 TI - [The effect on chewing of treating distal bite with an activator]. AB - The aim of this study was to analyse the influence of activator treatment on chewing efficiency. The subject material consisted of 60 children, adolescents and adults: Twelve children (ten years of age) with a Class II, Division 1 malocclusion were treated successfully with activators to a normal occlusion (16 years of age). Three normal occlusion samples, ten years (n = 12), 16 years (n = 12) and 29 years (n = 12) of age as well as an untreated Class II sample (n = 12), 16 years of age, served as control groups to the activator patients. The chewing ability was evaluated with the aid of a chewing efficiency test. The dental occlusion was appraised on dental casts. Recordings were made of number of erupted teeth, number of intermaxillary occlusal tooth contacts, overjet and overbite. The results revealed that chewing efficiency in activator patients was doubled from ten to 16 years of age. When comparing untreated subjects 16 years and ten years of age a greater chewing efficiency was seen in the older subjects. This was true for both Class II malocclusion and normal occlusion cases. Furthermore, in 16 year old subjects the chewing efficiency was comparable in treated and untreated normal occlusions as well as untreated Class II malocclusions. Thus, the investigation did not ascertain whether activator treatment per se resulted in an improved chewing efficiency. Furthermore, in the activator group no direct association existed between improvement in chewing efficiency and increased number of erupted teeth on one hand and increased number of intermaxillary occlusal tooth contacts, reduced overjet and overbite on the other. It is suggested that chewing efficiency is partly age related. The sagittal intermaxillary dental arch relationship doesn't seem to play an important role in determining chewing ability. However, harmonious interplay between the occluding teeth and the muscles influencing them (the muscles of mastication, the tongue-, lip- and cheek-musculature) is certainly of importance. PMID- 2583624 TI - [Isolated canine aplasia in monozygotic twins]. AB - This article describes isolated aplasia of the upper canines with retained deciduous canines in identical female twins. The twins are also concordant in some ectodermal stigmata. As a result of investigating other members of the family it appears that aplasia of the canines is due to a specific autosomal dominant gene. PMID- 2583626 TI - [Disorders of the sensitivity of the anterior teeth in children and adolescents]. AB - 1435 permanent incisors and canines were examined in 134 children and juveniles undergoing orthodontic treatment. Nearly 50% of the subjects had sustained trauma to their anterior teeth with equal numbers of boys and girls. Girls, however, were less often injured by direct contact. Pulp testing with dry ice from liquid CO2 showed disturbed sensitivity mainly of the upper anterior teeth. In the group with trauma the frequency of this phenomenon was increased compared to the group without trauma. The electric pulp tester did not prove suitable for sensitivity tests compared with dry ice testing. PMID- 2583625 TI - [Problems and characteristics of the orthodontic treatment of a patient with adrenogenital syndrome]. AB - This article describes biochemical relationships accompanying pathological symptoms of C-21-hydroxylase deficiency (adrenogenital syndrome). Disturbances of bone growth and development have been observed, even during medical treatment. A discrepancy of 2 1/2 years was noted between the patients chronological age and his bone development. The patient reaches a maximum height of 155 to 160 cm. Supernumeraries and delayed mineralisation are to be expected. Surgical procedures require an increase in cortisone dosage. When considering orthodontic treatment, one must determine the most appropriate time to start, take into account the long retention period and pay particular attention to oral hygiene. PMID- 2583627 TI - [Possibilities for the use of zonography in orthodontics]. AB - The "Zonarc" is a panoramic device in maxillofacial radiology that is programmed to cover different image layers. In this study human skulls of various sizes and various stages of development were examined with the aid of this equipment. The following projections were used: DENT program, JLA (special) program (TMJ side view, mouth open and closed), JSA program (TMJ sagittal, mouth open and closed). The positioning of the skulls as well as the correct adjustment of the equipment have been described on the basis of this investigation. The quality of reproduction of the skeletal tissue is discussed. The results indicate that the projections JLA and JSA can be used to advantage in orthodontic diagnosis. However one has to take the cost factor into consideration. PMID- 2583628 TI - [Early orthodontic treatment measures in infants with the EMG syndrome]. AB - In 1963 Beckwith and Wiedemann reported a syndrome, which was characterized by umbilical hernia, macroglossia and somatic gigantism. In the literature, early intervention by tongue reduction is recommended in order to prevent both mandibular prognathism and open bite. In this paper seven cases were presented showing that early functional treatment of the stomatognatic system leads to pleasing results, both functionally and aesthetically. Therefore it is suggested, that functional treatment should replace surgical management of macroglossia in the Beckwith-Wiedemann-syndrome. PMID- 2583629 TI - [Evaluation of the applicability of a mathematical model in the x-ray cephalometric diagnosis of sagittal bite anomalies. A clinical test]. AB - The mathematical model (Jarvinen) for measuring the sagittal difference between the maxillary and mandibular apical bases has been clinically tested. The material for this study consisted of 30 lateral skull radiographs of orthodontically untreated children (aged seven to 15 years) with different types of skeletal and/or dento-alveolar malocclusions. A comparison of the model with two conventional and two more developed methods to measure the sagittal apical base difference showed that the correlation between the new and the older methods increased as the errors of the older methods were eliminated. The results seemed to indicate that sagittal malocclusions could be accurately diagnosed by means of the model. PMID- 2583630 TI - [The Tubingen implant within the scope of adult orthodontic treatment]. AB - Prior to the replacement of a missing tooth with an implant the adult dentition, orthodontic treatment can be carried out to widen the space mesio-distally, correct the axial inclination of the neighbouring teeth and safeguard the anterior overbite. Implantation is not possible if, as a result of orthodontic treatment the gap cannot be widened to a minimum of at least 6 mm, if the alveolar bone is not thick enough in the vertical dimension or if the implant does not have sufficient space in the oro-vestibular direction. PMID- 2583632 TI - [Evaluation of inflammatory reactions following cataract surgery]. AB - Following cataract extraction 179 patients were examined with a slit-lamp using focal and specular illumination. 163 of them had received an intraocular lens (IOL). The cells (granulocytes) and flare-up in the anterior chamber decreased during the first postoperative days, while the cellular growth on the IOLs (macrophages) did not decrease in the same period. No correlations could be found between the cells, the flare-up in the anterior chamber, and the cellular growth on the IOLs. All three seem to be independent inflammatory reactions that occur following cataract extraction. PMID- 2583631 TI - [Risk factors for capsular rupture and vitreous loss in extracapsular cataract extraction. The Erlangen Ophthalmology Group]. AB - A prospective study of preoperative risk factors in extracapsular cataract surgery was undertaken. The study included 2042 planned extracapsular cataract extractions in 1772 patients performed by 12 surgeons between February, 1986 and June, 1988. The possible risk factors to be analysed included sex, age, right or left eye, axial length, pseudoexfoliation syndrome, preceding blunt ocular trauma, diabetes mellitus and systemic hypertension. Capsular breaks occurred in 2.9% and vitreous loss in 1.9% of our patients. A significant increase in the frequency of capsular breaks was observed for patients under the age of 41 and for patients with diabetes mellitus, vitreous loss being observed significantly more frequently in eyes with pseudoexfoliation syndrome. A slight but insignificant increase in capsular breaks was observed for male patients, left eyes, eyes smaller than 22 mm, pseudoexfoliation syndrome and systemic hypertension. Advanced age, myopia and previous blunt trauma were not found to be significant risk factors for capsular breaks or vitreous loss. We recommend careful preoperative patient examination to identify preoperative risk factors and possibly avoid intraoperative complications. PMID- 2583633 TI - [Lens opacities following pars plana vitrectomy]. AB - Lens opacities and particularly nuclear sclerosis belong to the most frequent complications after pars plana vitrectomy. Although the causative mechanism is not yet completely understood, the infusion cannula and infusion technique are likely to have important influence on the development of postoperative lens opacities. In order to reduce the flow of the infusion fluid directed to the posterior lens surface we developed a new cannula. Because of its posterior curvature and opening as well as a turbulent flow of the fluid the impairment of the posterior lens surface is diminished. To study the clinical efficacy of the new infusion cannula we examined 235 patients after pars plana vitrectomy during an observation period of 12 months. 14.7% of the total group developed progressive nuclear sclerosis. Significant cataract formation was much less frequent in eyes operated on because of macular pucker (7.3%). This is a lower incidence compared with other investigators. PMID- 2583634 TI - [Pigment dispersion following extracapsular cataract surgery with posterior chamber lens implantation]. AB - Pseudophakic bullous keratopathy is the leading indication for penetrating keratoplasty. Eight cases of postoperative corneal decompensation occurred during 1 year, five of them in 1 month. So far, three of these patients have received corneal grafts. None of the intraocular lenses were removed. Common symptoms are increased intraocular pressure in the immediate postoperative period, deposition of pigment on the corneal endothelium, long-lasting folds in the on descemet's membrane, edema of the corneal stroma, pigment dusting of the iris and anterior chamber angle. The potential role of the following factors is discussed: risk factors, infection, toxic reaction to the intraocular lens, antibiotics, Epinefrin and irrigation solution. The synonym "toxic solution syndrome" is proposed and discussed. PMID- 2583636 TI - [Experimental studies of the correlation of morphologic endothelial cell findings and endothelial pump function]. AB - In our experiments corneal endothelial cell morphology after Alizarin Red and Trypan Blue staining and endothelial pump function in a perfusion chamber were investigated. As a model for morphologically degenerated tissue we used corneas that had been cryopreserved with two different methods. In control groups 1) fresh, 2) one day organ cultured and 3) corneas without endothelium were evaluated. Morphologic evaluation showed degenerations (enlarged mononucleated cells, giant cells, disseminated necrotic areas) in cryopreserved corneas as compared with control groups. However, in perfusion experiments morphologically damaged tissue showed the same deswelling pattern as organ-cultured corneas. The results show that a morphologic evaluation seems to be a more precise criterion for the quality of the tissue than the investigation of the corneal pump function in a perfusion chamber. PMID- 2583635 TI - [Configuration of corneal incisions with the excimer laser: an experimental study]. AB - The potential applications of an ophthalmic excimer laser at 193 nm include its use as a precise trephine in keratoplasty procedures. In a series of 20 human autopsy and 40 pig cadaver eyes the histological and ultrastructural results of donor and recipient trephination and full-thickness corneal grafting using new mask systems were evaluated. In comparison with other beam delivery systems the "open mask system" allows the performance of excimer laser trephinations with reproducible wound configuration and geometry, with easy handling and high reliability. This technique enables the surgeon to surmount the mechanical limitations of cutting direction and makes non-circular trephinations possible. PMID- 2583637 TI - [Endothelial function in contact lens-induced deep corneal opacities]. AB - Deep stromal and preendothelial corneal opacities have been described to be a problem of growing importance in contact lens wearers, above all in those with a more than ten-year-old history of contact lens wearing. In the present study the corneal endothelial permeability of 21 patients with a more than ten-year-old history of contact lens (HEMA 38%) wearing has been determined and compared with that of an age-matched group of 8 healthy individuals without ocular disease. The corneal endothelial permeability has been measured by a computerized automated fluorophotometer (Coherent Radiation Fluorotron Master) after topical application of a Na-fluorescein solution according to the method described by Jones and Maurice. The corneal endothelial permeability of contact lens wearers with deep corneal opacities has been found to be significantly (p = 0.05) increased when compared with contact lens wearers without corneal opacities. Contact lens wearers without corneal opacities showed no significant increase of their endothelial permeability in comparison to the control group. PMID- 2583638 TI - [Long-term results of the treatment of Coats disease]. AB - Fluorescein angiographies and clinical data of 265 patients (292 eyes) with primary retinal teleangiectasis were retrospectively evaluated. If patients showed the typical pathology of the fundus and were less than or equal to 20 years, they were summarized under the diagnosis Coats' disease (125 eyes). These patients revealed significantly more severe vascular changes and exudates compared with older patients with retinal teleangiectasis. The treated and untreated course was compared in the group of patients with Coats' disease. Coagulation treatment and in some cases additional retina detachment surgery resulted in a significantly better course of the disease in contrast to the untreated group. The degree of the pathology of the fundus was the main factor for successful therapy. If the vascular changes regressed, the situation was stabilized for the following years. PMID- 2583639 TI - [Incidence and pathogenesis of ocular symptoms in HIV infection]. AB - 202 patients with HIV infections of different stages [1 (n = 59): symptomless HIV seropositivity, 2 (n = 64): pre-AIDS (LAS = Lymphadenopathy syndrome, ARC = AIDS related complex), 3 (n = 79): AIDS] were prospectively examined. The findings of the first examination were analyzed statistically in a cross-section-study. In 15 AIDS autopsy cases the eyes were examined histopathologically and with immunohistochemical techniques. Patients with stage 1 had only some Sicca syndromes (3%) and neuroophthalmological signs (dyscoria with neurosyphilis) (2%). 14% of the patients with stage 2 had a microvascular retinal syndrome, 11% a Sicca syndrome and 2% neuroophthalmological signs. Among the AIDS patients (stage 3), however, 61% had a microvascular syndrome of the retina, 24% a retinitis resp. choroiditis as an opportunistic infection (in 15% Cytomegalovirus was the causative organism), 16% had neuroophthalmological symptoms, 14% a Sicca syndrome and 5% Kaposi's sarcoma of the eyelids or conjunctiva. The microvascular retinal syndrome was found to be the most sensitive ocular indicator for an advanced stage of HIV infection. Further changes of the anterior eye segments (especially conjunctival vessel abnormalities and precipitates of the corneal endothelium in Cytomegalovirus retinitis) are demonstrated. PMID- 2583640 TI - [Macular coloboma and alternating diffuse chorio-retinal dysplasia]. AB - The author reports on two siblings. The elder, a 28-year-old woman has bilateral macular coloboma and a high degree of myopia. Her 27-year-old brother's left eye also has a macular coloboma, while his right eye has diffuse chorioretinal dysplasia with extensive nevoid choroidal pigmentation but no macular coloboma. His right eye is hyperopic, the left myopic. The eyes of the parents and their other, younger daughter are normal in all respects. Congenital syphilis and toxoplasmosis have been excluded as causes of the fundus deterioration of the first two offsprings. The macular colobomas of the two siblings (circumscribed macular dysplasia) and the alternating diffuse chorioretinal dysplasia must be classified as genetically conditioned maldevelopment of the optic cup ectoderm. PMID- 2583641 TI - [Amelanotic melanoma and nuclear magnetic resonance tomography--case report]. AB - In MRI choroidal melanoma shows a very short relaxation time (T2), shorter than that of any other intraocular tumor. This short T2 time is referred to the high concentration of paramagnetic melanine in this tumor. Therefore, it is of interest to measure the relaxation time in an amelanotic melanoma and compare it with the histological analysis. The duration of T2 for the amelanotic melanoma examined ranged from 130 to 160 ms. The small concentration of melanine is not a sufficient explanation, but it is possible that there are some precursors of melanine with paramagnetic characteristics. PMID- 2583642 TI - [Heliotherapy in iridocyclitis and intermediate uveitis]. AB - In a pilot in 1985 we treated 45 patients suffering from recurrent anterior uveitis with heliotherapy (Dead Sea, Israel), improvements were noticed in 40% of the probants during the following year. In a further clinical trial 14 patients (25 affected eyes) received treatment with heliotherapy twice for 3 weeks with a 12 months interval. The clinical findings showed a significant correlation between administration of the therapy and intermittent inflammation of the eyes. PMID- 2583643 TI - [Nonspecific eye autoantibodies in uveitis]. AB - Under certain pathologic circumstances autoantigens lead to the formation of autoantibodies. In uveitis, autoimmunologic phenomena will also be discussed. We studied 149 sera of uveitis patients for various organ specific and non-organ specific autoantibodies. We found antisarcolemal autoantibodies (ASA) mainly in patients with acute iritis (59% positive) but also in panuveitis (40%) and iridocyclitis (29%). On the other hand antiendothelial antibodies (AEA) could be found in 43% of patients with chorioretinitis. Antisinusoidal antibodies (SA) have been detected in iritis and panuveitis patients more often than in the control group which show positive autoantibodies in 5% of all cases. Using ELISA we looked for antibodies against keratin, laminin and microsomes. Because antimicrosomal-, antilaminin- and antisarcolemal-antibodies recognize the same epitope, there was a good correlation of these three autoantibodies. Similar clusters of autoantibodies (ASA, AEA and SA) have been found in various infectious diseases and in chronic inflammatory diseases in which an infectious component is discussed. These results may indicate that iritis, iridocyclitis, chorioretinitis and panuveitis are secondary reactions of eye tissue following a systemic primary disease. Especially viruses are well-known for their production of autoantibodies. In patients with intermediate uveitis we could not demonstrate these autoantibodies more often than in the control group, favouring theories which believe in an autoimmune reaction against vitreous elements. PMID- 2583644 TI - [Diagnosis of glaucoma using retinal nerve fiber photography]. AB - Clinical valuable retinal nerve fiber layer (RNFL) pictures are possible with every fundus camera when using the excitation or green filter. The conclusions follow by projection of the black-and-white print film. The more expensive production of paper prints is not always necessary for the judgement of the RNFL. RNFL-photography may facilitate the diagnosis and follow-up of optic nerve damages, especially the evaluation of eyes with an enlarged cup of the disk or of eyes with elevated intraocular pressure (IOP) without visual field defects. The damage of RNFL can be diffuse or localized. Diffuse damaging is difficult to detect. Localized RNFL-defects may be either slit- or grove-like and will be found in the upper and lower temporal arcuate. Slit like defects may be seen in normal eyes, too. RNFL-photography allows additional information in glaucoma suspect eyes. PMID- 2583645 TI - [Recording of visual evoked potentials in infants: characteristics and optimization of the method]. AB - As the capacities for concentration and fixation are limited in infants and young children it is necessary to adapt the method of VEP measurement. An appropriate stimulus presentation is the appearance, disappearance mode with sequentially presented gratings of different spatial frequencies. Variation in the conditions such as fixation, attention or electrode properties, during a recording session affects all cortical responses equally. The duration of VEP examination is shortened by using rapid sequences of stimuli. The purpose of our study was to improve the presentation of the stimuli. We used a small bright monitor (9 x 9 cm) for stimulation; the test distance was 60 cm, and the mean luminance 60 cd/m2. Stimuli were achromatic gratings. These parameters were chosen in order to compare the results of our method with psychophysical measurements, such as preferential looking (PL) with Teller acuity cards. The gratings with increasing spatial frequencies were presented in a sequence of 7 steps. In order to control the influence of artefacts and the variability of the responses summation/subtraction curve of the responses, was displayed simultaneously with the VEP on the control monitor. By increasing the temporal stimulus frequency in steps from 2.5 Hz (transient stimulus) to higher values we got excellent responses from on/off-stimuli at 5 Hz frequency. Thus the signal-to-noise-ratio was improved without alteration of the spatial transfer function which is found when using higher frequencies due to the Brucke-Bartley-effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583646 TI - [Direct superior oblique muscle trauma and dysfunction--surgical possibilities and results]. AB - Direct trauma to the superior-oblique muscle of the eyeball may result in active and passive ocular motility disturbance, e.g. paresis, Brown phenomenon, cyclorotation disorder, head-tilt and faulty head posture. In individual cases combinations of these and rather complex forms may occur. Surgery should aim at sufficient centralization of the binocular field of vision. The author usually recommends indirect procedures, at the ipsilateral inferior oblique muscle, to correct excyclorotation, or at the contralateral inferior rectus muscle to correct paresis. A pronounced Brown phenomenon should be treated by recession of the superior oblique muscle, or rather its transposition to the nasal side of the superior rectus. In addition, recession of the contralateral superior-rectus muscle or resection of the ipsilateral inferior-rectus muscle may be advisable. Out of eight patients, one refused surgery, five were sufficiently cured in one session, and another patient in three surgical sessions. One patient could not be satisfactority treated by surgery; in addition to a Brown phenomenon she had excyclorotation, especially in down-gaze, and paresis of the superior oblique muscle plus severe neuralgic pain in up-gaze. In this patient the trochlea had been accidentally lost during a foreign-body excision in the upper medial orbit. A secondary reconstruction of the trochlea was found not to be advisable in this patient, because the neuralgia was thought to be due to traction within the superior oblique tendon or the periost. PMID- 2583648 TI - The application of hard contact lenses in patients with congenital nystagmus. AB - From 1973 to 1987, 210 contact lenses were fitted in 112 patients with nystagmus and a refraction anomaly. In 79%, it was possible to correct myopia or a myopic or mixed form of astigmatism. In these cases, the visual acuity improved significantly. The hard contact lenses were well tolerated in all patients, and the intensity of the nystagmus can be reduced through this treatment. PMID- 2583649 TI - [Personal experiences with naturopathy. Liver diseases: success with plant extracts]. PMID- 2583647 TI - [Treatment of the dry eye with vitamin A acid--an impression cytology controlled study]. AB - To test the efficacy of topically applied tretinoin eyedrops (0.01%, twice daily, in a solution of peanut oil) in the treatment of squamous metaplasia of the conjunctival epithelium associated with dry-eye, the authors evaluated the impression cytology (IPC) of a total of 31 patients. The cytological findings were classified into four different stages with an overall range from 0 to 9 points. The average period of treatment was 12 weeks. The patients were classified into three groups: (1) Those with mucin deficiency (Mucin less than - greater than; n = 19), (2) those with Keratoconjunctivitis sicca (KSC; n = 6), and (3) a control group in whom pure peanut oil was used (n = 6). The IPC showed a considerable improvement of squamous metaplasia in the mucin less than - greater than group, by an average of 4.3 points (from 6.2 points before treatment to 1.9 points). No changes were seen in the IPC of the KCS patients or the control group. The results of this study show a good effect of tretinoin eyedrops in patients with a significant decrease in or loss of goblet cells seen in the IPC, a decreased break-up time and with no severe aqueous deficiency of tear film. These patients seem to have a "primary" mucin deficiency induced by the decrease in or loss of goblet cells. There is no indication for tretinoin treatment in patients with aqueous deficiency involving major or accessory lacrimal glands. The results of other previous and recent studies on tretinoin treatment are discussed. PMID- 2583650 TI - [Patient education in the treatment of bronchial asthma. Goals, content, pedagogic technics and evaluation of a structured program]. AB - Despite the advances in the understanding of the pathogenic mechanisms, clinical assessment and medical treatment of asthma, an increase of mortality and morbidity has been observed. It is clear from several studies, however, that this discrepancy may be at least partly due to serious short-comings, amongst asthmatic patients, in their ability to judge the severity of their asthma, and their knowledge of medication and correct dosaging, in the event of deterioration. Therefore, to effectively manage asthma structured education programs for adult asthmatics appear to be useful including information about the disease and the medication as well as training of self-management of airflow limitation by the patients. The evaluation of the course of the disease before and after this education revealed a reduction in severe attacks, hospitalization and days lost from work in trained asthmatics. PMID- 2583652 TI - [Treatment of acute hepatitis and its transformation into a chronic type]. PMID- 2583651 TI - [Recent topics on cell-membrane impairment by bacteriocidal substances--special reference to defensin and perforin]. PMID- 2583653 TI - [Management of HBs antigen carriers]. PMID- 2583654 TI - [Extents of daily activities allowed in chronic hepatitis and liver cirrhosis]. PMID- 2583655 TI - [Non-surgical treatment of liver cirrhosis and hepatic cancer]. PMID- 2583656 TI - [Surgical treatment of liver cancer]. PMID- 2583657 TI - A simple and efficient method for isolating genomic DNA from endomycorrhizal spores. AB - A procedure for rapid isolation of genomic DNA from spores of endomycorrhizal fungi is described. Isolation of high molecular weight DNA relies on the lysis of freeze-dried spores and extraction of DNA using mixed alkyl trimethyl ammonium bromide and an excess of proteinase. DNA greater than 30 kb was successfully isolated from Glomus mosseae, Glomus intraradices, and Glomus etnuicatum using less than 600,000 spores. All DNA preparations were suitable for restriction analysis, hybridizations, and cloning. PMID- 2583658 TI - An improved boiling method for the preparation of bacterial plasmid and phage DNA. AB - A streamlined, reproducible boiling method for preparing plasmid as well as phage replicative form DNA is described. Both quantity and quality of DNA purified are sufficient for restriction enzyme analysis and sequencing. A small loopful of bacteria will provide enough DNA for several experiments, and multiple samples can be processed and prepared for digestion or sequencing in under 20 minutes. DNA preparations are stable for at least 6 months at -20 degrees C. PMID- 2583660 TI - [Outline of daily instructions for diabetic patients]. PMID- 2583659 TI - An improved vector for the expression of proteins in all three translational reading frames. AB - We have constructed a novel vector (pN-7) that is capable of producing large amounts of recombinant proteins in E. coli and requires minimal manipulation for the construction of recombinant expression vectors. This expression vector (pN-7) contains the tightly regulated lambda pL promoter, cII ribosome binding site, and initiator condon ATG. The pN-7 vector also contains cleavage sites for the restriction enzymes SmaI, EcoRV, and HpaI that provide blunt ends in all three reading frames. Thus after cleavage with the appropriate restriction enzyme, this novel vector can be directly ligated to the DNA fragment that contains the open reading frame without further manipulation. PMID- 2583661 TI - [Diabetes and ocular complications]. PMID- 2583662 TI - [Diabetic neuropathies; new trends in physiopathology and treatment]. PMID- 2583663 TI - [Diabetic nephropathy]. PMID- 2583664 TI - [Relation of serum lipids disorders and ischemic heart disease in diabetics]. PMID- 2583665 TI - [Patient education for diabetics in the Hokkaido District]. PMID- 2583666 TI - [Nonthoracotomy internal defibrillation in dogs using a body surface electrode with a transvenous catheter electrode]. AB - The efficacy of truncated exponential waveform shocks using a cardioverter defibrillator catheter (Medtronic 6880) and body surface electrodes was examined in comparison with using a RV epicardial patch electrode and a LV epicardial patch electrode in fifteen pentobarbital-anesthetized dogs. The defibrillation thresholds (DFT) for 5 lead configurations were measured by the total energy, peak voltage and peak current: A) a body surface electrode (positioned at the right lateral chest wall) as the anode and a body surface electrode (positioned at the left lateral chest wall) as the cathode; B) a superior vena cava catheter electrode as the anode and a RV apex catheter electrode as the cathode; C1) a body surface electrode (positioned at left anterior chest wall) as the anode and a RV apex catheter electrode as the cathode; C2) a body surface electrode (positioned at the left lateral chest wall) as the anode and a RV apex catheter electrode as the cathode; and D) a RV epicardial patch electrode as the anode and a LV epicardial patch electrode as the cathode. The total energy at DFT for configurations C2 and D was lower than for configurations A, B, and C1, respectively (7.2 +/- 3.1 and 4.7 +/- 2.0 less than 18.9 +/- 3.8, 12.0 +/- 3.8 and 11.2 +/- 2.2 joules; p less than 0.05). The peak voltage at DFT for configurations C2 and D was lower than for configurations A, B, and C1, respectively (463 +/- 70 and 377 +/- 73 less than 767 +/- 85, 585 +/- 117 and 600 +/- 62 volts; P less than 0.05). PMID- 2583667 TI - [The oxygen dependence of the energy state of cardiac tissue--31P-NMR and optical measurement of myoglobin in perfused rat heart]. AB - The relationship between the energy state and intracellular oxygen concentration was established in the cardiac tissues, where the former could be monitored by 31PNMR and latter by optical method for myoglobin absorption. The ratio of creatine phosphate to inorganic phosphate (PCr/Pi), started to fall at 40 microM ofintacellular oxygen concentration. In contrast, intracellular pH and cardiac function started to fall at 10 microM of oxygen. By infusion of epinephrine (0.01 micrograms/min), myoglobin was deoxygenated concomitant with the increase of left ventricular pressure and heart heart rate increased. The oxygen dependence of Parameters described above were unchanged by epinephrine infusion. Araki et al. reported that oxygen consumption, the reduction of pyridine nucleotide, the increase of lactate release started to change at 10 microM and reduction of cytochrome a + a3 started to increase at 40 microM. These results suggest that there is near-equilibrium state in the respiratory chain and oxidative phosphorylation in the cardiac tissue. The decrease of oxygen consumption was compensated by PCr/Pi ratio and cytochrome a + a3. And this near-equilibrium was maintained when the respiratory rate increased. PMID- 2583668 TI - [Susceptibility of the Chinese hamster (Cricetulus griseus) to parasitic infection (3). Experimental infection with Hymenolepis nana or Trichuris muris to the cortisone treated Chinese hamster]. AB - Susceptibility of Chinese hamster (Cricetulus griseus) of Asahikawa Colony (CHA) to Hymenolepis nana or Trichuris muris infection was compared in the feces-egg examination with that of mice as the control animals. Though CHA were resistant to the infection of H. nana, they were found to become susceptible to H. nana by the treatment with cortisone. A half number of CHA was infected with H. nana and the eggs were detected from each animal only in 4 or 6 days in the periods of examination more than 40 days. Mice with or without cortisone treatment were equally susceptible to H. nana infection. In another experiment, CHA with or without cortisone treatment were completely resistant to Trichuris muris infection. Mice, as the control animals, were found to be infected with T. muris in both of cortisone-treated and non-treated groups. Results from the fecal examination, it was confirmed that T. muris were expelled naturally from the animals on the weeks of 11 to 33 after infection. PMID- 2583669 TI - Adrenalectomy in genetically obese ob/ob and db/db mice increases the proton conductance pathway. AB - Adrenalectomy (ADX) prevents the excessive weight gain in the genetically obese ob/ob and db/db mice. To test the possibility that this results from increased energy expenditure due to increased thermogenesis in brown adipose tissue (BAT), we measured GDP binding to mitochondria from interscapular brown adipose tissue (BAT) in db/db and ob/ob mice and their lean controls after adrenalectomy, with and without corticosterone replacement. Both the vehicle treated and corticosterone treated db/db and ob/ob mice had lower body weights than the sham operated mice GDP binding to mitochondria from IBAT was significantly lower in both the db/db and ob/ob mice than in their lean controls. Adrenalectomy significantly increased GDP binding in all mice compared to the respective sham operated mice, but, the percentage increase was always greater in the db/db and ob/ob mice. Corticosterone treatment of adrenalectomized db/db, ob/ob or lean mice lowered GDP binding to sham levels. Our data confirm previous findings that adrenalectomy results in increased GDP binding to mitochondria from IBAT. Injections of corticosterone into adrenalectomized mice results in a decrease in GDP binding to values which are similar to values in sham-operated mice. Thus adrenalectomy may inhibit the development of obesity by increasing the thermic activity in IBAT. PMID- 2583670 TI - Coordinated stimulation by triiodothyronine of fatty acid synthesis and isoproterenol-sensitive fatty acid release in two preadipocyte cell lines of lean or genetically obese mice. AB - The development and thyroid hormone sensitivity of fatty acid and triacylglycerol synthesis from 14C-acetate and of the isoproterenol-sensitive fatty acid release, were studied in two preadipocyte cell lines during the adipose differentiation: the Ob 17 and the HGFu cell lines cloned from the periepididymal adipose tissue of adult mice genetically obese and phenotypically lean respectively. Both parameters increased and peaked in the same time-period during the second week of culture after confluence. Both parameters were also amplified when T3 was added to the culture medium at confluence. The increment due to T3 was concentration dependent: it peaked at the physiological concentration of 1.5 nM and declined thereafter with the same pattern. This shows that some steps of two opposite pathways of lipid metabolism in differentiating preadipose cells can be stimulated by triiodothyronine in a similar manner and suggests a coordinated regulation. No significant difference could be detected between cells from lean or genetically obese mice. PMID- 2583671 TI - Distribution, composition and image analysis of plasma lipoproteins in steroid treated calves. AB - Six 8-day-old female calves were treated with a subcutaneous implant of 200 mg testosterone + 20 mg estradiol-17 beta. Thirty-five days following implantation, plasma lipoproteins were compared to those in control calves of the same age. The LDL exhibited a slight change in protein and lipid concentrations and no change in particle size. The effects of steroid therapy on HDL and particularly on the lighter density HDL were characterized by a reduction of densities associated with a decrease in protein content, and by a rise in lipids and an increase in particle size. The changes in HDL composition but not in LDL alterations were consistent with those associated with sexual maturation described previously. Although testosterone is the predominant component of our combined preparation, the effects of our treatment on young female calves is not consistent with the data reported for human lipoproteinemia. The high levels of urinary estradiol in treated calves suggest that these effects result more likely from the aromatization of the injected testosterone. PMID- 2583672 TI - Increased synthesis of prolactin and growth hormone during incubation in the pituitary of broody Nagoya hens. AB - Synthesis and release rates of prolactin and growth hormone (GH) in the anterior pituitary of laying and incubating broody chickens (Nagoya breed) were determined by a disc electrophoretic technique after in vitro incubation of anterior pituitaries with a labeled amino acid. Prolactin synthesis and release were two fold higher in incubating than in laying hens, resulting in twofold increase in the concentration of prolactin in the gland. GH synthesis was three-fold higher in incubating than in laying hens but GH release was not affected by the incubation. GH concentration in the pituitary gland also increased in incubating hens. It is suggested that these changes in hormone synthesis, release, and concentrations are related to nesting behaviour and nutritional condition of incubating hens. PMID- 2583673 TI - Does amiodarone inhibit T3 binding to solubilized nuclear receptors in vitro? AB - One of the proposed mechanisms of action of amiodarone is by interfering with T3 receptor interactions. However, reports in the literature on this matter are contradictory and, in an attempt to resolve these contradictions, the effects of amiodarone on T3 binding to solubilized nuclear receptors from rat liver were investigated. A drug concentration-related competitive inhibition of T3 binding occurred in the presence of considerable amiodarone precipitation. Measurement of the proportion of soluble amiodarone over the range where significant inhibition of T3 binding was observed, revealed that the soluble amiodarone decreased over this range. Since the amiodarone preparation was free of any contaminant, these findings suggested that a product generated from amiodarone during incubation was responsible for the inhibition. HPLC analysis of the soluble amiodarone fraction indicated that, during incubation, two substances were generated from the parent compound. However, only the concentration of one of the substances continually increased whereas the other decreased with increasing concentrations of amiodarone added to the samples. These findings suggest that the inhibition of T3 binding to solubilized nuclear receptors in the presence of amiodarone results from the generation of a specific product from the amiodarone under certain conditions during incubation. PMID- 2583674 TI - Actinomycin D inhibits the rapid increase in translatable calcitonin mRNA provoked by acute calcium stimulation. AB - Calcium, injected to rats, elicits a rapid increase in translatable calcitonin mRNA, by acting probably at the post-transcriptional level, as no change in calcitonin mRNA could be detected by hybridization assay. In this study we have measured calcitonin mRNA extracted from rats subjected or not to acute hypercalcemia and pretreated or not with actinomycin D. Calcitonin mRNA was quantified by its ability to direct the synthesis of calcitonin (CT) precursors in a cell free system and by hybridization to a 32P cDNA probe specific for CT mRNA. Actinomycin D, injected 5 hours before calcium administration, decreased the incorporation of 3H adenine in liver and thyroid, but did not inhibit the rise in plasma levels of calcium and CT (measured by radioimmunoassay). The antibiotic was able to inhibit the eightfold increase in translatable mRNA elicited by calcium administration in the control animals. Hybridizable CT mRNA levels were not modified by the treatments. Thus the increase in translatable CT mRNA after calcium stimulation is independent of CT secretion and is probably due to post-transcriptional modifications involving the expression of other gene(s). PMID- 2583675 TI - Maternal, amniotic fluid and cord blood metabolic profile in normal pregnant and gestational diabetics during recurrent withholding of food. AB - In order to advise regarding the religious practice of withholding food, we studied the metabolic changes after successive 15 days of recurrent fasting of 13 hours every day in maternal plasma and liquor amnii of obese normal gravids and gestational diabetics in their third trimester. There were no significant differences between those who fasted that period for one day prior to elective cesarean section (CS) and those who fasted the same period repeatedly for 15 days. The fasted gravids had significant rises in glycerol, beta-hydroxybutyrate (BOHB) and nonesterified fatty acids (NEFA) (P less than 0.0001, P less than 0.005 and P less than 0.01, respectively) in maternal plasma, compared to unfasted gravid groups and ungravid fasted group. No significant metabolic difference was found in the liquor amnii withdrawn from fasted and unfasted groups. The influence of such short term of starvation on the fetal metabolic profile was studied in the cord blood during cesarean section (CS). Glucose, glycerol and NEFA were significantly lower in arterial than in venous cord plasma (P less than 0.05, P less than 0.01 and P less than 0.01, respectively) indicating that the fetus could utilize these substrates. Positive correlation was found between the levels of BOHB in the mother and venous cord plasma on the one hand and their levels in the arterial cord plasma and liquor amnii on the other hand implying that this substrate passes unutilized through the fetus to the liquor amnii. A pregnant woman in the third trimester should not withhold food for long periods. PMID- 2583676 TI - A comparison of the thermogenic effects of CRF, sauvagine and urotensin I in the rat. PMID- 2583677 TI - McCune-Albright syndrome with acromegaly. PMID- 2583678 TI - Association of primary sclerosing cholangitis and celiac disease: fact or fancy? PMID- 2583679 TI - Alcohol infusion to measure hepatic blood flow: vanquishing the bete noire? PMID- 2583680 TI - Gallstone pancreatitis: when is the optimal time for intervention? PMID- 2583681 TI - Portacaval anastomosis: the longest shunt. PMID- 2583682 TI - Impaired sulfoxidation in primary biliary cirrhosis. PMID- 2583683 TI - Treatment of patients with benign recurrent intrahepatic cholestasis. PMID- 2583684 TI - Timing of postprandial hemodynamic events in cirrhosis. PMID- 2583685 TI - Chronic delta hepatitis: detection of hepatitis delta virus antigen in serum by immunoblot and correlation with other markers of delta viral replication. AB - To investigate the presence of serum hepatitis delta virus antigen by immunoblot and its correlation with other markers of active viral replication (intrahepatic hepatitis D antigen, IgM antibody to hepatitis D and serum hepatitis D virus RNA), we studied serum samples from 50 patients with chronic hepatitis D virus infection (38 with and 12 without intrahepatic hepatitis D antigen). Of the 38 patients with intrahepatic hepatitis D antigen, 27 (71%) had antigen detectable in serum by immunoblot, whereas only two were reactive by conventional enzyme linked immunosorbent assay. Thirty-one (82%) patients were also positive for serum hepatitis D virus RNA by spot hybridization and 33 (87%) were positive for IgM anti-hepatitis D virus. All markers were simultaneously present in 24 patients. Circulating hepatitis D antigen was detected in one (8%), IgM anti hepatitis D in seven (58%) and hepatitis D virus RNA in two (17%) of the 12 patients who had anti-hepatitis D in serum but not detectable hepatitis D antigen in liver. Hepatitis D antigen was not detected in serum of any of the 15 control patients. The results suggest that serum hepatitis D antigen as detected by immunoblot and serum hepatitis D virus RNA are similar in sensitivity for detection of active hepatitis D virus replication during chronic infection and constitute useful, sensitive and noninvasive tests for the diagnosis and monitoring of chronic hepatitis D virus infection. PMID- 2583687 TI - Soluble interleukin 2 receptor in acute viral hepatitis and chronic liver disease. AB - Serum levels of soluble interleukin 2 receptor were determined in patients with acute viral hepatitis and patients with various chronic liver diseases. In addition, the ability of peripheral blood mononuclear cells of patients with alcoholic cirrhosis to generate soluble interleukin 2 receptor following mitogenic stimulation was studied in vitro. Serum soluble interleukin 2 receptor concentrations in all patients with acute viral hepatitis were found to be significantly elevated (1,319 +/- 527 units per ml) during the first week after onset of disease, as compared to healthy control individuals (375 +/- 102 units per ml; p less than 0.0005) and declined toward normal levels during the course of the illness. Similarly, patients suffering from chronic liver disease such as alcoholic liver cirrhosis (1,172 +/- 507 units per ml), primary biliary cirrhosis (619 +/- 190 units per ml) or chronic active HBsAg+ hepatitis (941 +/- 357 units per ml) showed increased serum soluble interleukin 2 receptor concentrations (p less than 0.0005 vs. controls, respectively). In vitro mitogen stimulation of peripheral mononuclear cells derived from patients with alcoholic cirrhosis resulted in a soluble interleukin 2 receptor production not different from that seen in healthy individuals, suggesting that elevated soluble interleukin 2 receptor serum levels seen in this disease are not the result of an increased synthesis by circulating lymphocytes. Due to the ability of soluble interleukin 2 receptor to bind free interleukin 2--thus making it a potential immunoregulatory molecule--its high serum levels could explain some of the immunologic abnormalities observed in acute and chronic liver disease. PMID- 2583686 TI - In vitro replication and expression of hepatitis B virus from chronically infected primary chimpanzee hepatocytes. AB - Primary chimpanzee hepatocytes were maintained in vitro utilizing a serum-free medium. Hepatocyte functions were sustained throughout the culture period as demonstrated by the synthesis and secretion of liver-specific plasma proteins characteristic for differentiated hepatocytes. Hepatocyte cultures established from a chimpanzee chronically infected with human hepatitis B virus exhibited the synthesis and secretion of hepatitis B virus proteins into the medium. In addition, the de novo replication of hepatitis B virus was documented by the recovery of virus, exhibiting an endogenous DNA polymerase activity, from the tissue culture medium. Therefore, both the long-term maintenance of differentiated hepatocytes and the expression of hepatitis B virus from these primary cultures were sustained in the serum-free medium. PMID- 2583688 TI - The rat liver microcirculation in alcohol-induced hepatomegaly. AB - It has been suggested that hepatocyte enlargement can lead to compression of the extracellular space (sinusoidal and interstitial) and induce portal hypertension. However, this hypothesis has never been tested by measuring the vascular and extravascular spaces in the intact liver. The aim of the present study was to investigate the effects of chronic alcohol intake on the hepatic microcirculation using Goresky's multiple-indicator dilution technique in the isolated perfused rat liver. Female rat littermates were pair-fed either ethanol (n = 7) or an isocaloric carbohydrate diet (n = 7) for 21 days. As expected, chronic alcohol intake produced a significant increase in liver/body weight ratio (+32%, p less than 0.01) and hepatocyte size (+45%, p less than 0.001), which was accompanied by a marked increase in the cellular water space (control: 3.3 +/- 0.6 ml; ethanol-fed: 4.9 +/- 0.9 ml; p less than 0.001). When expressing data per total liver, the sinusoidal space was similar in the two groups (control: 1.87 +/- 0.2; ethanol-fed: 1.95 +/- 0.2 ml; not significant), whereas the interstitial space was increased in alcohol rats compared to controls (albumin space +58%, p less than 0.01; sucrose space +51%, p less than 0.01). In alcoholic rats, the sinusoidal space was probably stretched, with an overall reduced transversal diameter, as suggested by the reduced values found when data were expressed per gm of liver weight. However, despite this finding and the enlargement of the liver and hepatocytes observed in alcoholic rats, similar values were obtained between the two groups for the portal perfusion pressure and thus the intrahepatic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583689 TI - Effect of ethanol on splanchnic hemodynamics in awake and unrestrained rats with portal hypertension. AB - Alcoholic liver disease is frequently accompanied by portal hypertension. We have previously shown that alcohol intake in awake, unrestrained rats is followed by an increase in portal tributary blood flow. In this study, the effect of ethanol on splanchnic hemodynamics in rats with portal hypertension was analyzed. Portal hypertension was induced by partial ligation of the portal vein. This procedure resulted in an increase in portal tributary and hepatic arterial blood flows compared to sham-operated animals. Ethanol (2 gm per kg, oral) increased portal tributary blood flow in both sham-operated and portal vein-ligated rats (sham + water = 37.6 +/- 1.4; sham + ethanol = 63.1 +/- 1.9; p less than 0.01; partial portal vein stenosis + water = 53.2 +/- 3.3; partial portal vein stenosis + ethanol = 69.5 +/- 2.2 ml.kg-1.min-1; p less than 0.01). In sham-operated rats, hepatic artery blood flow was unchanged following ethanol (sham + water = 6.6 +/- 0.7; sham + ethanol = 7.1 +/- 1.0 ml.kg-1.min-1), whereas in portal vein-ligated rats, flow was increased (partial portal vein stenosis + water = 13.7 +/- 1.4; partial portal vein stenosis + ethanol = 19.8 +/- 1.1 ml.kg-1.min-1; p less than 0.025). The adenosine receptor blocker 8-phenyltheophylline suppressed only the ethanol-induced increase in both portal tributary and hepatic artery blood flows in portal vein-ligated rats. The increases in hepatic artery and portal tributary blood flows observed in portal vein-ligated rats without ethanol were not influenced by 8-phenyltheophylline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583690 TI - Propranolol decreases portal pressure without changing portocollateral resistance in cirrhotic rats. AB - Propranolol decreases portal pressure by reducing portal blood inflow. Studies in rats with prehepatic portal hypertension due to portal vein stenosis (a model with extensive portosystemic shunting) have shown that propranolol increases the portocollateral resistance, which hinders the fall in portal pressure. The present study examined the effects of propranolol on splanchnic and systemic hemodynamics in rats with portal hypertension due to cirrhosis of the liver, a model which is characterized by mild portosystemic shunting. Two groups of rats with CCl4-induced cirrhosis were studied: the propranolol group (n = 8), which received a propranolol infusion of 2 mg per 15 min, and controls (n = 9), which received a placebo (saline) infusion. Hemodynamic measurements were done using radiolabeled microspheres. Propranolol-treated rats had significantly lower cardiac output (-31%) and heart rate (-26%) than controls (p less than 0.001). Hepatic artery flow was not modified by propranolol. Propranolol caused splanchnic vasoconstriction, manifested by increased splanchnic resistance (+57%) and by a significant fall in portal blood inflow (4.8 +/- 0.4 vs. 6.3 +/- 0.5 ml per min.100 gm in controls, p less than 0.05). In contrast with rats with prehepatic portal hypertension, propranolol did not increase portal resistance in cirrhotic rats [2.0 +/- 0.2 vs. 2.0 +/- 0.1 mmHg per ml per min.100 gm body weight (not significant)]. Hence, the fall in portal pressure (-19%) was expected from the decrease in portal inflow (-24%). These results suggest that increased portal resistance in rats with prehepatic portal hypertension may represent an intrinsic effect of propranolol on the portocollateral vessels, since beta blockade does not modify portal vascular resistance in cirrhosis. PMID- 2583691 TI - Rejection in liver transplantation. AB - One hundred four liver transplant recipients were retrospectively reviewed for the incidence of liver allograft rejection, the response to antirejection therapy and the impact of rejection on graft and patient survival. Liver biopsies were performed weekly during episodes of graft dysfunction and to follow response to treatment. Baseline immunosuppression consisted of cyclosporine and low-dose prednisolone. Rejection was treated with steroids and with OKT3 as rescue. Azathioprine was given to patients with preoperative or perioperative renal insufficiency and was added to patients' treatment after the first sign of rejection. Seven complications were observed in approximately 1,100 liver biopsies, only one necessitating surgery. We found that 39.4% of the patients never experienced acute rejection, and 60.6% had at least one episode of acute rejection. Overall, 42.3% of the patients had only one episode of acute rejection, 13.5% had two, 3.8% had three and 1% had five episodes of acute rejection. Sixty of 63 first acute rejection episodes occurred within 21 days of transplant. Primary disease, sex or patient age had no significant influence on the incidence of rejection. There was a lower incidence of rejection (p less than 0.005) in patients transplanted after October, 1986, despite lower mean cyclosporine levels. Mean cyclosporine level during the first postoperative month was 679 ng per ml vs. a mean level of 910 ng per ml prior to October, 1986, when the immunosuppressive protocol was altered. Antirejection therapy was very effective in that only two of the 63 patients had graft failure due to acute rejection. Both of these patients were subsequently retransplanted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583693 TI - MA hospitals suffer from physician fee limits. AB - Massachusetts laws restricting physician fees are creating problems for hospitals as well. The physician shortage that the restrictions have created is resulting in emergency department overloads and rising lengths of stay in hospitals outside the Boston metropolitan area. PMID- 2583694 TI - Community concerns stall hospital closure. AB - Closing Leland Memorial Hospital, Riverdale, MD, would end the financial problems that the 120-bed facility faces. But a coalition of local government officials, physicians, and community leaders is successfully using the not-for-profit mission of the system that owns the hospital and its tax-exempt status as weapons to keep the hospital open. PMID- 2583692 TI - Interaction of hemopexin, albumin and liver fatty acid-binding protein with protoporphyrin. AB - Equilibrium constants for the binding of protoporphyrin to serum albumin and hemopexin and liver cytosolic fatty acid-binding protein of the rat were determined fluorometrically. The experimental equilibrium constant [10(6) M-1 (mean +/- S.D.)] values were 8.4 +/- 1.3, 10.0 +/- 2.4 and 34.0 +/- 3.0 for albumin, hemopexin and liver fatty acid-binding protein, respectively. Statistical analysis showed the equilibrium constant of binding of protoporphyrin to liver fatty acid-binding protein to be significantly (p less than 0.01) higher than that to albumin and hemopexin. The data suggest that in patients with erythropoietic protoporphyria an equilibrium gradient may exist which favors the uptake by hepatocytes of plasma protoporphyrin as a result of its greater affinity for intracellular liver fatty acid-binding protein. PMID- 2583695 TI - Hospitals see threats from patients and doctors. PMID- 2583696 TI - Peer review, privileges: MDs fear legal tangles. AB - Physicians are watching--and worrying about--a variety of new liability concerns generated by changing credentialing practices in hospitals. In fact, liability from peer review actions is the foremost legal concern of today's physicians. PMID- 2583697 TI - The data bank: final regulations. PMID- 2583698 TI - Be aware, not afraid, of JCAHO complaint standards. AB - How does your hospital handle complaints? You better have a good answer to this question. As of this January, the Joint Commission on Accreditation of Healthcare Organizations, Chicago, will require hospitals to formalize their methods of responding to patient complaints. PMID- 2583699 TI - Chief operating officers: increasingly choice positions. AB - Traditionally viewed as a steppingstone to the CEO position, today's chief operating officers (COO) are experiencing dramatic changes in their jobs. As our cover story notes, the emphasis is on operations, and the ideal COO is an an individual who likes dealing with people, managing them, and increasing productivity, say executive recruiters. But the number of COO job slots appears to be decreasing, according to a recent survey. And competition for the available jobs is increasing as more burned-out CEOs begin to look favorably at step-down positions. Also, don't miss our exclusive nationwide survey data profiling the hospital's number-two job. PMID- 2583700 TI - Hospital's number 2s--who they are, what they do. PMID- 2583701 TI - Pain programs offer opportunities for hospitals. AB - Easing pain and suffering has always been hospitals' business. But recently some hospitals have begun to treat the management of pain as a business in itself. And programs that treat both the physical and psychological aspects of pain are bringing in profits and new patients. PMID- 2583702 TI - No smoking: punitive words for addicted patients. AB - No smoking. These words are becoming common in hospitals, which are increasingly turning smoke-free. But for the patient who smokes, these words only add stress to what is already a trying situation. Now, some hospitals are offering patients bedside support programs to ease their nicotine addiction. PMID- 2583703 TI - Physician-to-physician accountability aids UR. Interview by Mary T. Koska. AB - Robert J. Becker, M.D., risked his house, his pension, and all the assets from his 26-year medical career to start Health Care Compare, Inc., a Downers Grove, IL, utilization review (UR) company. Since then, Becker has seen that risk pay off. His method of employing physicians as part of the UR team is an attempt to alleviate some of the anxiety physicians have about the UR process. PMID- 2583704 TI - CA price competition hot despite fewer contracts. AB - Negotiating hundreds of managed care contracts to protect market share may soon be a thing of the past for large California hospitals, according to an ongoing study by the Rand Corp., Los Angeles. But this doesn't mean that price competition is slowing down in the state, experts say. PMID- 2583705 TI - EDI: electronic management is almost a reality. AB - Electronic data interchange (EDI) is the computer-to-computer transmission of business data in a standard format. But EDI is not just a method for sending purchase orders to a few vendors more rapidly, say executives. It can be a business-management methodology that could be utilized in every hospital department. PMID- 2583706 TI - Suppliers promote new EDI frontiers. PMID- 2583707 TI - One contract alters small-town market balance. AB - What happens when the largest employer in a small community of 30,000 contracts with one provider's HMO network? Ask hospital executives in Sherman, TX. The exclusive contract, which marks the debut of managed care in the community, has shifted the balance of the local health care market. PMID- 2583708 TI - American Express caters to cautious clients. AB - American Express Information Services Co. (ISC), St. Louis, assures former clients of McDonnell Douglas Health Systems Co., Hazelwood, MO, that they have nothing to fear from the April 1989 acquisition. In fact, McDonnell Douglas's former clients are in the hands of a company that believes computer purchasers, such as hospitals, are underserved and deserve more support from their vendors. PMID- 2583709 TI - Growth in outpatient PT services aids consumers. AB - More physical therapy is being offered outside the hospital setting, and health care experts expect this trend to continue as providers plan to expand their services to meet the needs of an increasingly fitness-minded, health-conscious society. In addition, don't miss the exclusive consumer data on who's using physical therapy services. PMID- 2583710 TI - Leadership style: what works, how to change. AB - What's the most important leadership quality: charisma, vision, or a "take charge" personality? All of the above, according to executive recruiters. The passive leadership styles that were acceptable in the past are out. Today's boards are looking for more active, visible leaders. PMID- 2583711 TI - Brownisms: words of wisdom on management style. AB - The management philosophies and accomplishments of the distinguished hospital administrator and professor Ray E. Brown (1913-1974) will be described in a new book, which is scheduled to be published in April 1990. Some of his "Brownisms" are previewed in this issue. PMID- 2583712 TI - Detection of HIV genome in HIV antibody negative men. AB - The presence of the human immunodeficiency virus (HIV) genome was investigated by applying in situ hybridisation techniques to peripheral blood mononuclear cells (PBMCs). Twenty asymptomatic anti-HIV seronegative homosexual men were the subjects of our study. The cells were hybridised with: (1) an SP 64 plasmid containing the nine-kilobase SstI-SstI viral insert from the lambda BH 10 recombinant clone; this can recognise both viral RNA and proviral DNA, and (2) with a pA01 plasmid containing HBV DNA genome. The DNA probes were modified by inserting an antigenic sulfone group in the cytosine moieties and the visualisation was performed by a double antibody immunohistochemical reaction. In two subjects both the HIV genome and HBV DNA were detected whereas another two subjects were positive for HBV DNA and for the HIV genome respectively. Thus people who are seronegative for anti-HIV specific antibodies may be infected with HIV. PMID- 2583713 TI - Rheumatoid factor in congenital syphilis. AB - The rheumatoid factor (RF) latex test was evaluated as a test for congenital syphilis. High risk newborns of mothers with untreated or inadequately treated syphilis were studied. The asymptomatic infants were followed up for between 3 and 4 months (or longer if the VDRL test was positive). The overall performance of the RF latex test was better than that of the other tests studied, even though the sensitivity was 46.7%. The specificity and positive predictive value of the test were 100% whilst the negative predictive value was 86.4%. The test was negative in all 84 controls studied. Although a negative RF latex test cannot be used to exclude congenital syphilis in an asymptomatic infant, a positive test in the presence of maternal syphilis should lead one to strongly suspect congenital syphilis. PMID- 2583714 TI - Early yaws, imported in The Netherlands. AB - Early yaws in a 9 year old girl from Ghana, diagnosed as imported disease in The Netherlands is reported. She had lived in The Netherlands for six months. Tropical non-venereal treponematoses are rarely seen in Europe, and only a few case reports have been published. Migration and travelling may confront the medical profession with cases of tropical diseases such as yaws. Positive serological reactions in non-venereal tropical or venereal treponematoses cannot be distinguished at present. PMID- 2583715 TI - Evaluation of a radioactive rRNA:cDNA-hybridisation assay for the direct detection of Chlamydia trachomatis in urogenital specimens. AB - A radioactive cDNA probe complementary to chlamydial ribosomal RNA was used to detect C trachomatis in urogenital specimens. Of 37 specimens positive with cell culture 31 were confirmed by the rRNA:cDNA hybridisation test, the sensitivity being 83.8%. The specificity of the hybridisation test was 94.4%, as 186 of 197 specimens that were negative by cell culture were also negative when assessed by the hybridisation method. Given a prevalence of 15.8% the predictive values for positive and negative results were 73.8% and 96.9%, respectively. In additional experiments the possible role of microorganisms added to the specimen collection medium was investigated. However, no indication for crosshybridisation was found; at high concentrations microorganisms interfered with the test procedure. PMID- 2583716 TI - VIth African Regional Conference on sexually transmitted diseases. PMID- 2583718 TI - Syphilitic myelopathy. AB - Whether the clinical pattern of neurosyphilis has changed since the introduction of penicillin is controversial. This study describes the clinical, laboratory and radiological features of nine patients with syphilitic myelopathy, to assess whether the disease pattern has changed in this subgroup. Four patterns based on clinical course and radiological findings were identified: three patients presented with subacute paraparesis, four with prodromal backache and/or mild leg weakness followed by sudden paraplegia, one patient developed slowly progressive weakness over 4 years and one patient who progressed over one month was shown to have dural thickening on myelography. All patients showed CSF pleocytosis with positive CSF VDRL in seven patients. Despite therapy the prognosis for recovery was not good. Compared with pre-penicillin era studies, the clinical pattern has not significantly changed. Greater alertness to the diagnosis might result in earlier therapy and thus possibly lead to improved prognosis. PMID- 2583717 TI - White piedra and Trichosporon beigelii: the incidence in patients attending a clinic in genitourinary medicine. AB - To assess the occurrence of white piedra and the asymptomatic carriage rate of T beigelii, 100 heterosexual and 49 homosexual/bisexual men were entered into the study. White piedra of the scrotal hair was discovered in a total of four (2.7%) patients (two heterosexual, one homosexual and one bisexual), while in addition a positive scrotal culture for T beigelii was noted in a further seven (4.8%) patients (four heterosexual and three homosexual). Rectal carriage rates were 1% in the heterosexual and 4% in the homosexual/bisexual groups, while there was no pharyngeal carriage in either group. PMID- 2583719 TI - Changes in incidence of STD among heterosexual patients: fear of AIDS? PMID- 2583720 TI - Evaluation of abnormal cervical cytology results in a genitourinary clinic. PMID- 2583722 TI - Pedal error and misperceived centerline in eight different automobiles. AB - The hypothesis that misperception of an automobile's centerline is related to pedal error was tested in eight late-model automobiles. Pedal error is described as hitting the accelerator pedal when instructed to depress the brake pedal. One hundred twenty-nine subjects participated in an experiment in which pedal errors and perceived centerline were measured in all eight automobiles. The results indicate that subjects misperceive the centerline of the automobile to be to the right of the actual centerline. Although 26 pedal errors were recorded, no relationship between pedal errors and misperceived centerline was found. PMID- 2583721 TI - Treating chancroid: summary of studies in South Africa. PMID- 2583724 TI - Effect of prior headlighting experience on ratings of discomfort glare. AB - This study investigated the effects of prior headlighting experience on ratings of discomfort glare from headlamps in an actual driving situation. Specifically, discomfort glare ratings given by West Germans who had recently arrived in the United States and were, presumably, used to the relatively low levels of glare associated with headlamps in West Germany were compared with ratings given by U.S.-born subjects. The West German subjects reported significantly more discomfort than did the U.S. subjects. This finding is in agreement with the so called range effect, in which subjective judgments are affected by the range of available stimuli. Consequently, the present findings support the hypothesis that discomfort glare ratings are affected by prior visual experience. PMID- 2583723 TI - Perception of risk in automotive systems. AB - Thirty subsystems constituting a functioning motor vehicle, including brake, steering, suspension, engine, electrical, and fuel systems, were evaluated by individuals on a set of risk characteristic scales. These included overall vehicle riskiness, manufacturer's anticipatory knowledge of system defects during vehicle design, likelihood of severe consequences in the event of system failure, controllability of the vehicle, and observability of impending failure. An analysis of the resulting judgments revealed two composite factors, one representing the controllability of consequences and the other representing observability. Both factors were highly related to judgments of risk, desire for risk regulation, and anticipated recall compliance. A comparison of risk judgments with accident data suggested that for some vehicle systems, particularly those serving a communication function in the driving task, drivers may underestimate the actual risk they face when system performance has degraded. PMID- 2583725 TI - Effects of handle angle and work orientation on hammering: I. Wrist motion and hammering performance. AB - This research investigated the range of wrist motion characteristics associated with the ergonomic principle of "bending the tool and not the wrist" as applied to the hammer. It is thought that bending the tool reduces angular wrist motion, which has been shown in the literature to be a risk factor in hand/wrist disorders such as carpal tunnel syndrome and tenosynovitis. Hammer handles angled at 0 (straight), 20, and 40 deg were investigated in this study. For novices, hammer handles bent at 20 and 40 deg resulted in less total ulnar deviation than straight hammers. However, there was a trade-off in beginning and ending positions of the wrist in that the angled hammers reduced ulnar deviation at the impact position but increased radial deviation at the starting position of a hammer stroke. Handle angle did not significantly affect hammering performance. Wrist motion was affected minimally by hammering orientation, but hammering performance was significantly worse in the wall orientation compared with the bench orientation. This research suggests that for novice users, hammers with handles bent in the range of 20 to 40 deg could possibly decrease the incidence of hand/wrist disorders caused by hammering. PMID- 2583726 TI - Effects of handle angle and work orientation on hammering: II. Muscle fatigue and subjective ratings of body discomfort. AB - This research investigated how changes in hammer handle angle and hammering orientation affected muscle fatigue in the forearm and subjective ratings of body discomfort. Forearm muscle fatigue and discomfort ratings were not significantly affected by handle angle, but they were significantly higher in the wall hammering orientation than in the bench orientation. The research in this article and in the companion article (Part I) reveal that for novices, hammers with handles angled in the range of 20-40 deg are advantageous because (1) they reduce ulnar deviation and may possibly decrease the incidence of hand/wrist disorders, and (2) they do not significantly affect hammering performance in the bench conditions, forearm muscle fatigue, or subjective ratings of body discomfort. PMID- 2583728 TI - Training effects on the resolution of moving targets--dynamic visual acuity. AB - In initial 60-min sessions, the dynamic visual acuity (DVA) of 54 male college observers was determined over a range of target velocities (60, 90, 120, and 150 deg/s) at each of three durations (200, 400, and 600 ms). Following four 30-min practice sessions with the task, a final test session identical to the first was then conducted. Highly significant training effects on DVA were obtained; contrary to previous work, these effects were most marked for observers with initially poorer performance. PMID- 2583727 TI - Arm posture and human movement capability. AB - Many workers perform manual assembly tasks or use hand tools while the hands are postured above the shoulders or to the side of the body. Experiments were conducted to study the sensitivity of speed-accuracy movement performance to a wide range of hand locations around the shoulder under various levels of hand loads, ratios of work to rest, and task durations. Subjects performed a spatially constrained stylus-to-hole Fitts reciprocal movement task designed to simulate high-incentive manual assembly operations while providing basic information regarding changes in human move and positioning capabilities. Significant decrements in movement performance occurred when hands were postured above shoulder level. Move and positioning times increased 15.3% and 26.5%, respectively, with elevation of the hand from -15 to 60 deg respective to shoulder level. Posturally based decrements in movement capability were unrelated to differences in subject strength capability found among test postures. The consequences of elevated arm postures on human move and positioning capability are presented along with workplace design and methods recommendations for job designers facing work-height decisions in manual assembly environments. PMID- 2583729 TI - Liver alcohol and aldehyde dehydrogenase isozymes in a Chinese population in Hong Kong. AB - The distribution of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isozymes in the livers of a Chinese population in Hong Kong was examined. Among the 90 livers examined, 7 were typical ADH phenotype consisting the normal beta 1 type isozymes and 83 were atypical phenotype consisting the beta 2-type isozymes. Livers of 48 subjects were of deficient type in ALDH containing ALDH-II alone and 42 were of normal type with both ALDH-I and ALDH-II. When the combination of ADH and ALDH isozymes is considered, the Chinese population in Hong Kong falls into 4 subgroups. For each group, the rates of ethanol and acetaldehyde clearance have a distinct and characteristic potential which is directly related to its particular combination of isozymes. PMID- 2583730 TI - HLA antigens, blood groups and serum protein groups in patients with intermittent claudication. AB - HLA (A and B) antigens, blood group systems (AB0, Rh, MNSs P, Kell, Lewis and Duffy) and serum group systems (Hp, Tf, Pi, C3 and C4) were studied in patients with intermittent claudication (IC) and controls. HLA antigen A 28 was significantly more common, and blood group 0 was significantly less common among the patients than among the controls. A comparison between patients with IC and those with abdominal aortic aneurysms showed a significant difference between these two groups concerning the MN blood groups. PMID- 2583731 TI - Commingling in the distributions of immunoglobulin levels. AB - Commingling in the distributions of five immunoglobulins from a Canadian sample of 810 Caucasians and IgE from a US sample of 935 Caucasians was investigated. For both the Canadian and US samples significant commingling was found in the child's but not the adult's IgE distribution. Contrary to expectations based upon the major gene hypothesis for IgM, we found no evidence for commingling in the IgM distribution. Finally, the distributions of IgA, IgD and IgG all evidenced significant commingling that may be the result of a single gene effect or the operation of a discrete environmental effect. PMID- 2583732 TI - Estimates of conditional heterozygosity risks for young females in Duchenne muscular dystrophy. AB - Using the data from daughters of known carriers and from age-paired controls, we present a method for estimating the mean and variance of creatine kinase (CK) and pyruvate kinase (PK) in pre-menarchal and early adolescent Duchenne muscular dystrophy (DMD) carriers. CK and PK means and variances were estimated for different age ranges; it is shown that among DMD carriers the levels of both enzymes decrease linearly with age. A discriminant analysis was further performed for the estimation of biochemical risks favouring the diagnosis of heterozygosity for possible young carriers. The use of this method may also be applicable for other X-linked conditions in which the detection of heterozygotes is probabilistic. PMID- 2583733 TI - Family resemblance for glucose tolerance in a Melanesian population, the Tolai. AB - Path analysis of family resemblance for plasma glucose concentration, 2 h after an oral glucose challenge, failed to detect significant genetic heritability. There were no intergenerational differences and marital resemblance was moderate. Over one-third of sibling environmental similarity was due to non-inherited factors. Cultural inheritance was very strong, tending to mimic genetic inheritance, and cultural heritability was considerable. Measures of obesity were included in the environmental index, an estimate of familial environment, in this analysis, for comparability with previous studies. Since obesity appears, in part, to be a heritable trait, in future studies a bivariate approach to family resemblance for both glucose tolerance and obesity could yield important additional insight. PMID- 2583735 TI - Distribution of blood groups in Korea. AB - Eight populations in the southern part of the Korean peninsula were studied to elucidate their genetic structure and to understand the genetic relationships between them. For this purpose, several blood groups and other genetic markers were analyzed. In total, over 9,000 blood specimens were collected. About 2,000 specimens were tested for 9 blood groups. The gene frequencies were estimated as A = 0.2555, B = 0.2244, O = 0.5201, M = 0.5263, S = 0.0560, d = 0.0472, C = 0.6542, E = 0.3126, Fya = 0.9210, Jka = 0.4386, Dia = 0.0539, P1 = 0.1939, K = 0.0010, Le = 0.6866 and Se = 0.6311 in the total sample. A continuous variation was observed for the frequency of gene B. PMID- 2583734 TI - Distribution of plasma alpha-1-B-glycoprotein phenotypes in several Mongoloid populations of East Asia. AB - The distribution of plasma alpha 1B-glycoprotein (alpha 1B) phenotypes was determined by a simple method of two-dimensional electrophoresis followed by protein staining in a group of 1,154 individuals from 8 Mongoloid populations of East Asia. The sample comprised 581 Chinese from different localities (Singapore: 204; Taiwan: 150; Fujien and Hopeh provinces of eastern China: 146 and 81), 155 Koreans, 155 Filipinos, 152 Thais and 111 Malays. Altogether, 6 different alpha 1B phenotypes (1-1, 1-2, 2-2, 1-3, 2-3, and 1-6) were observed. The alpha 1B allele frequencies were very similar in all of the populations. The frequency of A1B*1 varied from 0.89 to 0.91 and that of A1B*2 from 0.08 to 0.10. The A1B*3 allele, reported previously only in American blacks, was observed with a frequency range of 0.003-0.01 in 3 of the Chinese populations, in Koreans and in Malays. A new alpha 1B allele (A1B*6) was observed in 2 Chinese individuals. PMID- 2583736 TI - Population studies in northern Sweden. XVI. GC subtypes. AB - The frequencies of group-specific component (GC) subtypes were studied in a population of 4,053 conscripts and blood donors from the counties of Vasterbotten and Norrbotten in northern Sweden. The individuals were distributed according to place of birth into 23 subpopulations. A significant heterogeneity between the 23 regions was observed for the GC*1F, GC*1S and GC*2 genes, and clines were found for all genes. The frequency of the GC*1F gene was increasing in the northern direction, and the frequencies of the GS*1S and GC*2 genes were increasing in the southern direction. The geographical pattern of the GC*1F gene frequency could be explained in terms of Lappish influence. PMID- 2583738 TI - [Ulcerating herpes analis: cardinal symptom for manifest immunodefects in HIV infections]. PMID- 2583737 TI - Regulation of total leukocyte, neutrophil and lymphocyte concentrations in human blood by major effectors. AB - Commingling analysis of total leukocyte, neutrophil and lymphocyte concentrations in human blood suggested the effect of major regulatory factors affecting each type of white blood cells. Our results showed two distributions for the total leukocyte and lymphocyte concentrations. The values of the low and high phenotypes were 5.8 and 8.4 x 10(9)/l of total leukocytes and 2.0 and 4.6 x 10(9)/l of total lymphocytes. On the other hand, the neutrophil concentration in blood is probably regulated by equally penetrant factors. The means of the three phenotypes were 2.6, 4.2 and 6.5 x 10(9)/l. The evidence of two or three phenotypes, although consistent with the effect of a single-factor hypothesis (genetic or environmental), must be confirmed by segregation analysis of families. PMID- 2583739 TI - [Zidovudine prolongs the survival time of AIDS patients with PCP]. PMID- 2583740 TI - Assessment of immunological parameters during tumour development in a murine model. AB - Natural Killer activity assessed by 51Cr release assay from K-562 cells showed detectable activity from 5th day after tumour transplantation, reaching a peak on 12th day and thereafter showing a gradual decline in the activity. Antibody dependent cell mediated cytotoxicity estimated by 51Cr labelled sheep red blood cells anti SRBC system demonstrated a peak activity on 5th day. Cytotoxic T lymphocyte activity detected by 51Cr release of Dalton's lymphoma ascites target cells showed a peak on 10th day. Antibody complement mediated cytotoxicity revealed a similar pattern as natural killer cell activity. PMID- 2583741 TI - Uterine and placental 5-HT profile in different gestational period of albino rats. AB - Possible role of 5-HT in pregnancy was investigated in albino rats by biological estimation of uterine and placental 5-HT contents in different periods of gestation in normal and drug treated rats. Uterine 5-HT level increased steadily from day-1 of gestation to reach the peak on day-7; thereafter, the level continued to decline throughout the period till day-20 when 5-HT level was lowest. From day-20, a mild secondary rise started and remained persistent even after parturition. The results show that a critical level of 5-HT in early gestational period is necessary for conception. Manipulation of endogenous 5-HT do not influence duration of gestation. PMID- 2583742 TI - Ultrastructural and biochemical changes in epididymis and vas deferens of gossypol treated rats. AB - Adult male Wister rats when administered with 15 mg/kg body weight/day of gossypol acetic acid proved to be sterile by 10 weeks of treatment. The weight of the whole epididymis did not deviate from the controls but when the caput, corpus and cauda epididymidis were considered separately, the cauda epididymidis weight was significantly reduced. The major changes were observed in the motor apparatus of the sperm. The most common defects in the sperm were the vacuolization and complete degeneration of the midpiece mitochondria and plasma membrane. The total LDH activity of caput and cauda epididymidis were within the range of control values. Sialic acid levels of the epididymis were not affected after the treatment. These results suggest a more proximal site of action of the drug than at the epididymal level. PMID- 2583743 TI - Serum and thyroid tissue lipids in patients with thyroid tumors in euthyroidism. AB - Plasma lipids of 24 euthyroid subjects with thyroid adenoma and non-toxic primary differentiated thyroid carcinoma (papillary and follicular types) were assessed and compared with a similar investigation conducted on 20 normal subjects. A parallel study with thyroid tumor tissues examined the lipid changes which occurred in the same group of patients. These were compared with the picture seen in 5 normal thyroids. The investigations examined the changes in total lipids; total, free and esterified cholesterol; total phospholipids; lecithin; cephalin and sphingomyelin; triglycerides and free fatty acids in both serum and thyroid tissue. Compared with normal subjects, the serum lipids were almost identical except for the concentration of free fatty acids which showed significantly lower values in the group with neoplastic changes. Tissue analysis of the cancerous thyroid however revealed a marked rise in virtually all lipid fractions but the cholesterol seemed to dominate the picture. The differential studies of total phospholipids for thyroid tissue membrane lipids further revealed a significant increase in the lecithin and sphingomyelin components of total phospholipids as well as the esterified cholesterol fraction in thyroid carcinoma. The changes in thyrophospholipids were more marked in females normal thyroids than males. An attempt has been made through evaluation of the results derived from differential lipid studies to elucidate the role of some of the various fractions determined and the possible effect of the changes described on thyroid hormone metabolism. PMID- 2583744 TI - Platelet serotonergic mechanisms and glomerulonephritis. AB - Proven cases (28) of glomerulonephritis (GN) were evaluated for clinico biochemical profile, bleeding time, platelet count, platelet aggregation and platelet serotonergic mechanisms. Inordinate increase in platelet aggregation and altered platelet serotonergic mechanisms (reduced 5-HT, uptake, reduced intraplatelet 5-HT and increased plasma 5-HT) were demonstrated in some histopathological types of GN. The mechanisms and importance of these alterations have been discussed. PMID- 2583745 TI - Pharmacodynamic studies on Polypodium vulgare (Linn.). AB - Aqueous extract of the root of P. vulgare (PV) produced CNS depressant effect. It decreased the spontaneous motor activity, prolonged the pentobarbitone induced hypnosis, reduced body temperature and increased the reaction time to pain stimuli. PV also caused prevention against supramaximal electroshock and pentylenetetrazol induced seizures. PV showed a positive inotropic and chronotropic effect on perfused frog heart and caused hypotension and tachycardia in anaesthetised dogs. The effects were blocked by propranolol. PV produced dose dependent inhibition of contractions of rabbit small intestine and the effect was blocked by propranolol. PV appears to possess CNS depressant and beta adrenoceptor agonistic activities. PMID- 2583746 TI - Pharmacology of Acorus calamus L. AB - Water soluble dried powder of alcoholic extract of roots and rhizomes of A. calamus L. was used. The in vivo experiments involved strychnine convulsant activity in frogs, spontaneous motor activity and amphetamine hyperactivity in mice, pentobarbitone sleeping-time in rats and local anaesthetic activity in guinea pigs and rabbits. Frog skeletal muscle and heart preparations and rat phrenic nerve diaphragm constituted the in vitro experiments. Plant extracts at 10, 20 mg/kg ip did not afford protection to strychnine (1,5,2.5 mg/kg) induced convulsions and same effect was found on acetylcholine induced contractions of rectus muscle except that it inhibited caffeine citrate contractions in frog. At 1, 10 and 100 micrograms/ml doses, it caused negative iono- and chronotropic effects in frogs. Dosages of 10, 25, 50 mg/kg ip of herbal extract antagonize spontaneous motor activity and also amphetamine induced hyperactivity in mice. It was less potent than chloropromazine, though exerts sedative and tranquilizing action. Local anaesthetic activity was found to be absent at 0.5 and 1% dose levels. PMID- 2583747 TI - Effect of intracerebroventricular administration of angiotensin II on emetic reflex in dogs. AB - Area postrema is rich in angiotensin II receptors and intravenous (iv) administration of angiotensin II has been reported to elicit emesis. However, in the present study intracerebroventricular (icv) administration of angiotensin II up to a dose of 10 micrograms failed to elicit emesis. It is suggested that presence of a cerebrospinal fluid-brain barrier in area postrema most probably prevents access of icv angiotensin II to its receptors which are otherwise accessible on iv administration. PMID- 2583748 TI - In vitro proliferation of murine spleen cells: I. Strain variation of response to medium from cultures of EL-4 cells. AB - Proliferative responses of murine lymphoid cells were elicited in vitro with supernatant fluid from cultures of EL-4 thymoma cells stimulated with phorbol ester. It was demonstrated that such responses depend on IL-2 contained in the supernatant fluid, but reflect co-stimulation with IL-2 and phorbol ester. Striking differences in the magnitude of proliferative responses of spleen, splenic T lymphocytes, thymus and bone marrow cells from various strains were observed. Three classes of responders could be identified. The differences in responsiveness, at least in part, reflected differences in the frequency of responsive cells and were genetically controlled by codominant alleles of two independent somatic genes. PMID- 2583749 TI - Protection against a syngeneic mammary adenocarcinoma by administration of idiotypic and anti-idiotypic antibodies. AB - A hybridoma secreting a monoclonal antibody (mAb) with specificity for tumor associated cell surface antigens of a transplantable murine mammary adenocarcinoma (SMC-168) was prepared by fusion of syngeneic C3H/He spleen cells with SP2 myeloma cells. Mice which were pretreated with this mAb (C-73) were significantly resistant to the outgrowth of a tumorigenic dose of SMC-168 cells when compared to controls. The treated mice developed tumor-specific cell mediated immunity, measured by leukocyte adherence inhibition (LAI), which was equal to that of mice immunized with live tumor cells. The IgG fraction from serum of mice receiving mAb C-73 contained antibodies which would bind to that mAb suggesting the presence of anti-idiotypic antibodies (anti-Id). This binding could be partially inhibited by a soluble 1-butanol cell surface extract of SMC 168. Rabbits were immunized with mAb C-73 to produce a polyclonal anti-Id. The purified and absorbed IgG fraction of this serum would bind only to mAb C-73 and not to other mAbs of the same isotype or normal C3H/HeN IgG. Binding of the rabbit anti-Id to mAb C-73 could be partially inhibited by soluble tumor associated antigen extracted from SMC-168. Mice immunized with this polyclonal anti-Id vaccine developed tumor-specific cell-mediated immunity and were significantly resistant to the outgrowth of a tumorigenic dose of SMC-168. PMID- 2583750 TI - Effects of corticosterone on responses of murine splenic B and T cells to phytohemagglutinin, concanavalin A, and lipopolysaccharide. AB - Spleen cells of C57BL/6 mice injected with corticosterone were compared with cells from mice injected with saline in their ability to respond to the mitogens PHA, Con A, and LPS. Both unseparated cells and cells separated into T-enriched and B-enriched fractions were studied. After either seven daily injections or four injections every other day of up to 100 mumoles hormone/kg body weight, the ability of both T and B cells to respond to mitogens was affected, the unseparated cells being more affected than the separated cells. In the whole spleen preparations, corticosterone seemed to inhibit the B cells more than the T cells, whereas when the cells were separated into T and B fractions, only the response of the cells in the T fraction was significantly reduced by the hormone. This suggests that this hormone may have a greater effect on the responsiveness of T cells than on B cells, whereas it reduces B cell number more than T cell number. PMID- 2583751 TI - Soluble interleukin 2 receptors released from mitogen stimulated human peripheral blood lymphocytes bind interleukin 2 and inhibit IL2 dependent cell proliferation. AB - In this communication the binding characteristics and possible regulatory role of sIL2R were investigated. Soluble IL2R are released or secreted in high concentrations by phytohemagglutinin (PHA) stimulated human lymphoid cells. The addition of sIL2R, purified by gel filtration chromatography, to cultures of PHA stimulated lymphoblasts resulted in a dose-dependent inhibition of [3H]TdR incorporation that could be overcome by the addition of exogenous IL2. Scatchard analysis of IL2 binding demonstrated that the presence of sIL2R did not inhibit ligand interaction with the high affinity IL2R. Immunoprecipitation studies utilizing [125I]IL2 and the non-inhibitory anti-Tac protein antibody 7G7/B6 revealed that most of the 125I-labeled IL2 migrated with a protein of approximately 45-50 kDa on SDS/PAGE. Together, these results provide evidence that the sIL2R limits the availability of free IL2 to proliferating cells and down-regulates their response without directly affecting the number or function of the cell bound high affinity IL2R. PMID- 2583752 TI - Effect of anesthesia on the immune system: suppression of the immunogenic capacity of macrophages and of lymphocyte transformation. AB - Experiments were carried out aimed at investigating the effects of anesthesia without surgery on certain functional components of the immune system. We observed that the immunogenic antigen-presenting capacity of mouse peritoneal macrophages was significantly reduced one week post-anesthesia, with either injected or inhaled anesthetic drugs. On the other hand, an augmentation of the phagocytic activities of these macrophages was manifested. Hence, the impaired immunogenic potency could not be attributed to a reduced antigen uptake. Lymphocyte transformations, i.e., response to PHA and Con A were suppressed, whereas the response to LPS was augmented. PMID- 2583753 TI - Oxidative burst capability of human monocyte subsets defined by high and low HLA DR expression. AB - There is a wide range in the expression of major histocompatability complex (MHC) class II HLA-DR molecules on freshly isolated human peripheral blood monocytes from one individual. This study determined whether the variability in HLA-DR expression on monocytes correlated with their oxidative burst capability after treatment with either phorbol myristate acetate (PMA) or calcium ionophore A23187. Freshly obtained cells were incubated with 2',7'-dichlorofluorescin diacetate (DCFH-DA), a dye which is utilized for the determination of cell oxidative potential by flow cytometry. Cells were stimulated, and then stained with phycoerythrin (PE)-labeled monoclonal antibodies (mAb). Two-color flow cytometry was used to determine changes in DCFH-DA (green) fluorescence which corresponded to oxidative product formation by cells which stained only with the PE-labeled mAb (monocytes). While monocytes with a high or low surface density of HLA-DR differed substantially in HLA-DR expression, only small differences in oxidative capability between "high" and "low" subsets were observed. Thus, monocytes which are very different in HLA-DR expression possess very similar oxidative burst capabilities. PMID- 2583754 TI - The Madurai experience in preventing nutritional blindness. PMID- 2583755 TI - Effectivity of colloidal ferric salt in childhood iron deficiency anemia. PMID- 2583756 TI - Supplementary iron dose in pregnancy anemia prophylaxis. AB - This study was conducted to determine the optimum dose of supplemental iron for prophylaxis against pregnancy anemia. One hundred and ten pregnant women were randomly allocated to three groups: Group A receiving equivalent of 60 mg, group B 120 mg and Group C 240 mg, elemental iron as ferrous sulphate daily; the content of folic acid was constant in all the three groups (0.5 mg). These women had at least consumed 90 tablets in 100 +/- 10 days. Blood was drawn at the beginning and at the end of the treatment. Fifty percent were anemic (less than 11 g/100 ml). The hemoglobin levels rose similarly in all groups and the differences were statistically not significant. Fifty-six percent had depleted iron stores (serum ferritin value less than 12 micrograms/l) at the beginning of the study. Following therapy a statistically significant increase in iron stores was observed in group B and C as compared to group A. The difference between group B and C was not significant. The side effects increased with increasing doses of iron; 32.4%, 40.3% and 72% in group A, B and C respectively. Based on these findings, the authors advocate that optimum dose of iron should be 120 mg instead of 60 mg as is currently being used in the National Nutritional Anemia Prophylaxis Programme. PMID- 2583757 TI - Determination of gestational age: comparative accuracy of different methods. AB - One hundred new-born infants were studied in an attempt to test the accuracy of selected methods of post-natal assessment of gestational age. The Finnstrom method using seven external characteristics was found to be relatively more accurate both in preterm and term infants. Dubowitz and Cappuro method were accurate in premature infants only. However in a limited number of post-term infants Cappuro method yielded better results. The Finnstrom method can be recommended for routine assessment of gestational age. PMID- 2583758 TI - Effect of chlorine gas leak on the pulmonary functions of school children. AB - Pulmonary function tests (PFT) were performed on 84 children studying in a Municipal School, near a plant manufacturing chemicals in Chembur, a suburb of Bombay, from where large amounts of chlorine gas leaked out on 30th August, 1985. It was found that only 23.8% had normal PFT's. 66.7% showed an obstructive pattern and 9.5% showed a restrictive pattern of PFT's. This is a preliminary report to establish the prevalence of lower PFT values in children staying in an area of air pollution in Bombay. PMID- 2583759 TI - Cryptosporidium causing chronic diarrhea. AB - The authors report a case of a child with chronic diarrhea due to Cryptosporidium. The child had also hemolytic uraemic syndrome. Cryptosporidium oocysts were identified by the modified Ziehl-Neelsen technique. PMID- 2583760 TI - Prevalence of cryptosporidium in children with acute diarrhea. AB - Cryptosporidium is an intestinal protozoa known to cause diarrhea in animals and more recently has been recognised as a cause of diarrhea in humans. The present study was designed to determine the prevalence of cryptosporidium as a cause of diarrhea in children. Faecal samples of 180 children admitted to the hospital for acute gastroenteritis and from 100 normal children were analysed. Eight out of 180 (4.4%) stools from children with acute diarrhea and none from normal showed cryptosporidi. We conclude that this parasite does play a role in the etiology of human diarrhea. PMID- 2583761 TI - Edward syndrome with multiple chromosomal defects. PMID- 2583762 TI - Cyclopic malformation in infants of diabetic mothers. AB - Two cases of cyclopic malformations are described among 450 infants of diabetic mothers during a period of four years. Both died within 30 min. of birth. Both belonged to unrelated Libyan families with absent consanguinity and family history. No chromosomal defect was found in either. A possible etiological association with uncontrolled maternal diabetes is discussed. PMID- 2583763 TI - Primary cerebral rhabdomyosarcoma. AB - Primary intracranial rhabdomyosarcomas are extremely rare tumors; those in the supratentorial location are commoner in adults. A 10 year old girl with primary cerebral rhabdomyosarcoma is presented. PMID- 2583764 TI - Teaching and learning pediatrics. PMID- 2583765 TI - How we teach and how they learn. AB - Residents need to learn how to assess and accommodate to a variety of behaviors and affective styles presented by patients and their families. This requires those skills which enable them to facilitate interactions with people in a positive, effective, and efficient manner. The teaching of these interpersonal and communication skills should incorporate a multi-disciplinary model. The development and implementation of a successful resident training program requires careful attention to the establishment of goals and objectives, learning activities and evaluation strategies that will meet the needs of the resident. The utilization of a multi-teaching, multi-media, and collaborative team approach intensifies the effectiveness of the overall training program. This article describes a training program that focuses on communication skills while being mindful of the various settings in which residency training occurs. These include the use of video-tape of physician/patient interaction in continuing care clinic, communication with children in non-medical settings and audio-tape reviews of physicians telephone management in a pediatric emergency care setting. The evaluation instruments developed to assess interpersonal and communications skills are reviewed and discussed as an integral component of this educational and training model. PMID- 2583766 TI - Lecture skills in medical education. AB - The lecture is the most common method of transmitting information in medical schools and continuing medical education. In recent years this educational method has received considerable criticism because of poor lecturers and poor learning. The major advantage of the lecture is the ability to teach pertinent up-to-date information in an efficient manner. The major limitation is the passivity of the method with the teacher speaking and the listener passively receiving the material with considerable opportunity to be bored. The effective techniques of lecturing are: 1) environment aids learning: 2) an introduction perks interest; 3) stating objectives helps audience to respond analytically; 4) outlining a lecture helps clear thinking; 5) non-verbal behavior increases learning; 6) use of voice shows interest and clarity; 7) content is understood if it fits objectives; 8) organized lecture fits the time available; 9) visual aids used should be clear and understandable; 10) a summary helps to retain what is learned; 11) closure should be upbeat and should restate objectives; 12) questions should be answered succinctly. The medical lecturer can improve his skills by studying them, rehearsing while being observed by colleagues and by performing a self-analysis of video-taped lectures. PMID- 2583768 TI - Essential drugs in primary health care. PMID- 2583769 TI - Cryptosporidiosis--the Indian scene. PMID- 2583767 TI - Teaching technical skills in pediatrics. AB - Technical skills are an important and difficult part of managing a very sick or injured child. However, technical procedures are more often learned from experience than practice. This article reviews a variety of technical skills and procedures commonly performed in a pediatric emergency department. Each technical procedure can be practiced using live or artificial model for simulation. PMID- 2583770 TI - Multiple choice questions: how to construct and how to evaluate? AB - Multiple choice questions have come to occupy a prominent place in the evaluation system of medical education. However the framing of multiple choice questions and their effective use need further clarification in the Indian context. This paper outlines some of the steps that may be adopted for streamlining the preparation and administration of a multiple choice test and their scoring. A few tips have been given for getting the best from the candidates in a multiple choice examination. Lastly institutional mechanisms for developing MCQ bank have been suggested. PMID- 2583771 TI - Science and art of pediatric diagnosis. PMID- 2583772 TI - Chemotherapy research group for mother and child. PMID- 2583773 TI - Cholera gastroenteritis amongst children in Delhi. AB - Cholera gastroenteritis amongst 3595 children under twelve years suffering from acute watery diarrhea was studied for a period of five years (1982-86). V. cholerae 01 could be isolated from 31.7% of total specimens studied. Distribution in different age groups out of total gastroenteritis cases was 7.5% in less than 2 years, 13.1% in 2-5 years and 11.1% in greater than 5-12 years. Out of total cholera cases (1141 isolate) 23.4% occurred in the age group less than 2 yrs., 41.4% in 2-5 yrs. and 35.1% in greater than 5-12 yrs. Infection occurred more often in males in all the age groups. Throughout the study, cholera was observed during summer monsoon season with Ogawa being predominant serotype. PMID- 2583774 TI - Social stimulation of the severely malnourished child: a home training programme. PMID- 2583775 TI - Medullo epithelioma (diktyoma). PMID- 2583776 TI - Iatrogenesis in ophthalmology. PMID- 2583777 TI - "Present state of management of aphakia. Future of spectacles and contact lenses". PMID- 2583778 TI - History, developments and future thoughts of intraocular lens. PMID- 2583779 TI - Posterior peribulbar anesthesia: an alternative to retrobulbar anesthesia. AB - Peribulbar anesthesia is a safe alternative to retrobulbar anesthesia for ophthalmic surgery. Because the anesthetic is deposited outside the muscle cone, the potential for intraocular or intradural injection is greatly minimized. Furthermore, intraconal hemorrhage and direct optic nerve injury is avoided. We illustrate the details of our technique for posterior peribulbar anesthesia and describe our experience in over 3,000 cases. PMID- 2583780 TI - Lowering of intra ocular pressure--various methods. PMID- 2583781 TI - Methylcellulose--a better viscosurgical alternative for intraocular lens implantation. AB - The authors have used 2% methylcellulose in 8,000 cases of intraocular lens implant surgery during the last five and a half years. Their surgical experience and investigations have convinced them that methylcellulose is safe and effective besides being convenient and economical. It is easily autoclavable, has very low particulate matter when prepared by the author's technique, and causes minimal secondary rise of intraocular pressure. The endothelial protective function and breakdown of the blood aqueous barrier are comparable to that of Healon. The authors consider methylcellulose to be the better alternative for IOL implant surgery. PMID- 2583782 TI - Microsurgical instruments and their care. AB - The microsurgical instruments should be chosen such that they are less than 10 cm long, made of titanium, dulled, have very little closing pressure and the working parts do not open more than 10mm. They should be cleaned with ultrasonic cleaners and sterilised preferably by Ethylene oxide, though Cidex and dry heat can also be used. PMID- 2583783 TI - Extracapsular surgery. PMID- 2583784 TI - Anterior chamber intra ocular lens implantation. AB - The role of A.C. IOL in modern implant surgery has become somewhat debatable, since, the choice procedure to day is undoubtedly an ECCE with a PC lens implant preferably in the capsular bag. Even so, anterior chamber lens implantation has its definite indications. As such it is necessary for the implant surgeon to be familiar with the latest technique in this modality of surgery as well. Many of the complications of earlier rigid model AC IOLs were mainly due to defective lens design. With the advent of new generation flexible one-piece PMMA AC lenses, many of these complications have been eliminated. A.C. IOL implantation, although less frequently done now, has its own legitimate place in modern IOL surgery. PMID- 2583785 TI - Endo capsular insertion of intra ocular implant. AB - The first 500 posterior chamber lenses inserted in the capsular bag, have been analysed in detail. The cases included in this study were developmental, traumatic and complicated cataracts in addition to senile cataract. The follow-up ranged from 6 months to 2 years. Although posterior capsule rupture occurred in 23 cases, the lens was inserted in 12 cases with a small tear. In general the complications were found to be minimal and visual recovery was good in more than 80% of the cases. The only problems we have been facing were thickening of the posterior capsule (11.6%), high astigmatism (12.2%), pupillary capture (5.6%) and decentering of the lens (2.8%). PMID- 2583786 TI - Analysis of complications in 1000 cases of posterior chamber intra ocular lens implantation. AB - Analysis of complications in 1000 cases of primary posterior chamber intraocular lens implantation done, during a period of one year was undertaken for the study. The cases included uncomplicated as well as those with various associated conditions like diabetes, traumatic cataracts, complicated cataracts, myopia and developmental cataracts. The important postoperative complications were uveitis (9%), endophthalmitis (0.5%), malposition of IOL (2.8%) and cystoid macular edema (0.3%). Posterior capsule opacification was seen in 11.5% of cases and was treated by YAG laser capsulotomy. More than 80% cases had 6/6-6/12 vision. In our experience posterior chamber IOL implantation has become an extremely successful and satisfying procedure along with the availability of YAG laser facility to manage posterior capsule opacification. PMID- 2583787 TI - Phakoemulsification cataract extraction with foldable IOLs-first 50 cases. AB - Phakoemulsification as a procedure is only complete with flexible foldable lens. Preliminary studies show good acceptance of the procedure though the injector is cumbersome. Phakoemulsification has now become a reality with advanced instrumentation techniques available. Phakoemulsification has to its greatest advantage the ability to remove a cataract though a 3mm opening. Not only does this enhance the safety and the speed of healing, but it reduces postoperative astigmatism significantly. However, the very advantages listed above stand negated if the wound is to be opened to 6mm to accommodate an implant. The extra effort needed as compared to regular extra capsular cataract extraction, the enhanced cost of the instrumentation, the more sophisticated technique needed and the superior magnification devices required were all rendered negative till the flexible lenses made their debut. With foldable lenses, phakoemulsification has come into its own. Thomas Mazaco was first credited with the concept of folding and inserting lenses. The ocular lenses were foldable with a forcep (Faulker Folder) and inserted into the eye through a 4 mm incision. It was a tight fit and the compression exerted by the forceps often left a bend on the lens. These problems led to the manufacture of a injective inserter which was in essence a single metal syringe with a piston, either longitudinal pressure or screw movement. Of these the Bartel injector was perhaps the earliest. Now virtually every company making flexible lenses has come out with an injector. The Staar Softrans injector has proven in my hands to be the most useful of all these devices. PMID- 2583788 TI - Glass lens implant. PMID- 2583789 TI - Secondary IOL versus Epi-K. PMID- 2583790 TI - Intraocular lens (I.O.L) implant in traumatic cataract. AB - I.O.L. either primary or secondary has proved to be useful after traumatic cataract extraction. Problem of binocular single vision will be better solved and the traumatic eye becoming divergent and amblyopic can thus be avoided. PMID- 2583791 TI - Myopia and plasma cortisol. AB - Estimation of plasma cortisol by fluorometric technique desorbed by Mallingly's was carried out in 56 cases, including 38 cases of myopia (19 cases of simple myopia and 19 cases of degenerative myopia) and 18 normal individuals. Urinary 17 keto steroids/24 hours was also estimated by Zimmermann technique in 12 out of the 56 cases, which include 8 cases of myopia (4 cases of simple myopia and 4 cases of degenerative myopia) and 4 normal individuals as control. Plasma cortisol level is lower in simple and degenerative myopia than in normal subjects, but on statistical analysis the difference was not of much significance. Patients with simple myopia with positive family history showed lower value of plasma cortisol than patients with simple myopia with negative family history, the difference was also statistically insignificant (P-0.1). In degenerative myopia patients, with and without family history, there was very little difference in plasma cortisol level and statistically highly insignificant (P-0.8). Urinary 17 keto steroid/24 hour values are lower in simple and degenerative myopia than in normal subjects. PMID- 2583792 TI - Microbiological studies in conjunctivitis. AB - A total of 102 cases of clinically diagnosed cases of acute conjunctivitis were included in the present study. The sample was collected from the inflamed conjunctiva and was subjected to conventional bacterial and fungal cultural studies. The allergic element was found out by studying the smear after Giemsa staining and demonstrating increased number of eosinophils. The data revealed that 32 samples had an evidence of bacterial infection, 14 showed isolation of fungi and one displayed an allergic etiology. Thirty cases showed presence of mixed infection in different combinations while 25 samples were sterile on conventional culture media. Microbiological studies are essential for confirmation of clinical diagnosis and to institute an appropriate treatment. PMID- 2583793 TI - Ocular findings in the inmates of a leprosy rehabilitation centre. AB - This study is aimed at presenting the profile of ocular lesions observed in the inmates of a leprosy rehabilitation centre. Corneal involvement was found to be the highest (52.7%), followed by lesions of the eyebrows (47.3%) and eyelids (30.9%), uveal tract involvement (18.1%) and chronic conjunctivitis (1.8%). PMID- 2583794 TI - Bilateral tubercular lid abscess--a case report. AB - Tuberculosis is a ubiquitous disease and a public health problem of major importance in almost all countries. The disease can involve any part of the body. Eye involvement to tuberculosis is also common. A case of bilateral tubercular lid abscess without any active systemic involvement is being reported because of its rare occurrence. PMID- 2583795 TI - Hydatid cyst of the orbit with papilloedema. AB - A rare case of Hydatid cyst of the orbit causing, unilateral axial proptosis is reported. The presence of gross unilateral papilloedema misled us to the character of the cystic swelling causing axial proptosis. PMID- 2583796 TI - Race and gender influence ambulatory blood pressure patterns of adolescents. AB - The purpose of this study was to examine ambulatory blood pressure and heart rate patterns in healthy, normotensive adolescents and to determine the influence of race and gender on these patterns. Ambulatory blood pressure recordings were performed on 199 adolescents; 42 were black males, 55 were white males, 65 were black females, and 37 were white females. The mean age (+/- SD) was 13 +/- 2 years. Blood pressure readings were obtained with an automatic, noninvasive recorder. Black adolescents and white adolescents had similar blood pressures while awake (116/69 vs. 116/69 mm Hg), with boys having higher levels of systolic blood pressure (118 vs. 114 mm Hg) and comparable levels of diastolic blood pressure (69 vs. 69 mm Hg) relative to girls. The patterns while the adolescents were asleep, however, were different. White boys (106 mm Hg), white girls (105 mm Hg), and black girls (105 mm Hg) had similar systolic blood pressures during sleep. Black boys (112 mm Hg), however, had significantly higher systolic blood pressures while asleep. Black adolescents, as a group, had significantly higher diastolic blood pressures than white adolescents while asleep (64 vs. 61 mm Hg). Changes in blood pressure from awake to asleep were not related to changes in heart rate. Results of this study indicate that both race and gender are important determinants of the diurnal pattern of blood pressure and heart rate in adolescents. PMID- 2583797 TI - Lesions of the anteroventral third ventricle prevent salt-induced hypertension in the borderline hypertensive rat. AB - Many forms of experimental hypertension depend on the integrity of the periventricular tissue surrounding the anteroventral third ventricle. The current investigation examined the extent to which this forebrain area is necessary for the elaboration of salt-induced hypertension in the borderline hypertensive rat. Eight-week-old male rats were given either electrolytic lesions of the anteroventral portion of the third ventricle region or sham lesions. All rats were then placed on a high salt diet (8% NaCl) for 10 weeks. At the conclusion of this dietary period, direct measurement of resting mean arterial pressure revealed that borderline hypertensive rats with lesions of the anteroventral portion of the third ventricle had significantly lower blood pressure (128.4 +/- 5.1 mm Hg) compared with sham-operated rats (148.1 +/- 4.1 mm Hg). PMID- 2583798 TI - Hypothalamic GABA and sympathetic regulation in spontaneously hypertensive rats. AB - The posterior hypothalamus contains a sympathoexcitatory system that can be modulated by changes in GABAergic tone. We tested the hypothesis that the GABAergic mechanism in the posterior hypothalamus is altered in spontaneously hypertensive rats (SHR) compared with the Wistar-Kyoto (WKY) control rats. Blood pressure and heart rate were continuously measured in the conscious state; blood samples were obtained for determination of plasma catecholamine concentrations. Bilateral microinjections of the GABAA receptor antagonist bicuculline methiodide into the posterior hypothalamus increased heart rate and blood pressure in a dose related fashion and increased plasma catecholamine concentrations in both SHR and WKY rats. The responses were not significantly different between the two strains of rats. Microinjections of the GABAA receptor agonist muscimol in this same region caused dose-related decreases in both heart rate and blood pressure in SHR and WKY rats. Although the decreases in heart rate caused by muscimol were not significantly different between the SHR and WKY rats, the decreases in blood pressure were significantly greater in SHR compared with WKY rats. Further, microinjection of muscimol caused a significant decrease in plasma catecholamines in SHR but not in WKY rats. These data indicate that in SHR and WKY rats the posterior hypothalamus contains a sympathoexcitatory mechanism that is tonically inhibited by GABA. The ability of muscimol to decrease plasma catecholamines selectively in SHR and to cause greater decreases in blood pressure, suggests that the GABAergic mechanisms in the posterior hypothalamus of the SHR and WKY rats may differ. PMID- 2583800 TI - Long-term inhibition of angiotensin converting enzyme suppresses calcium channel agonist-induced contraction of aorta in hypertensive rats. AB - To elucidate functional changes in the vascular smooth muscle of spontaneously hypertensive rats (SHR) after chronic inhibition of angiotensin converting enzyme, we examined the contractile responses to different pharmacological interventions in the isolated aortas from SHR treated with a novel angiotensin converting enzyme inhibitor, CS-622 (10 mg/kg/day) for 20 weeks. In normal K+ medium, a marked contraction was elicited by increasing Ca2+ concentration from 0 to 3 mM in aortas from a control group of SHR, but not in aortas from SHR treated with CS-622. In 60 mM K+ medium, however, the sensitivity of aorta to Ca2+ was almost the same in the two groups. A calcium channel activator, CGP-28392 (10(-7) to 10(-6) M), induced a marked contraction in the aortas from control SHR, but not in the aortas from CS-622-treated SHR. When slightly depolarized in 10 or 12 mM K+ solution, the aortas from CS-622-treated SHR contracted in response to CGP 28392. The aortic sensitivity to KCl contraction was much lower in CS-622-treated SHR than in untreated SHR, whereas the sensitivity to phenylephrine contraction was little different in the two groups. These contractile profiles of aortas from CS-622-treated SHR were very similar to those from normotensive Wistar-Kyoto rats but not to those from hydralazine-treated SHR. These data suggest that contractions due to Ca2+ through voltage-dependent calcium channels are exaggerated in SHR aorta and that long-term treatment with angiotensin converting enzyme inhibitor suppresses the abnormal contractility of SHR vascular smooth muscle, probably through alterations of voltage-related functions of calcium channels. PMID- 2583799 TI - Role of endogenous brain kinins in the cardiovascular response to intracerebroventricular melittin. AB - Intracerebroventricular infusion of the peptide melittin increases immunoreactive kinins in the cerebrospinal fluid of anesthetized dogs, probably secondary to activation of brain or cerebrospinal fluid kininogenases. Intracerebroventricular melittin also increases blood pressure and heart rate, possibly mediated by brain kinins, since intracerebroventricular bradykinin also increases blood pressure and heart rate. We tested whether the effects of centrally administered melittin on blood pressure and heart rate could be blocked by simultaneous infusion of a kinin receptor antagonist, [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin, in normotensive awake rats. In the controls, intracerebroventricular infusion of kinin receptor antagonist given for 1 hour at a rate of 10 micrograms/hr blocked bradykinin induced increases in blood pressure and heart rate by 80%. Basal blood pressure and heart rate were not affected by the kinin receptor antagonist alone. After a 30-minute infusion of melittin (8 micrograms/30 min), cerebrospinal fluid kininogenase activity (n = 17) rose from 0.13 +/- 0.05 to 0.43 +/- 0.1 ng/ml/min (p less than 0.02). Although cerebrospinal fluid kinins increased from below sensitivity (0.02 ng/ml, n = 12) to 0.19 +/- 0.1 ng/ml (n = 17), this change was due to drastic increases in three rats, whereas in 12 of them kinins were below sensitivity. Incubation of bradykinin (10 ng) with 0.1 ml rat cerebrospinal fluid for 5 minutes destroyed 70% of kinins, suggesting that rapid destruction may have made detection of increased CSF kinins difficult.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583802 TI - Acute intestinal obstruction. AB - Nine hundred and four children with intestinal obstruction were studied. Necrotising enteritis was the commonest cause of intestinal obstruction in children. Acute intussusception was the second commonest cause in the whole group and the commonest cause in children under 1 year of age. Less common causes included band obstruction, sub acute intestinal obstruction and remnants of vitello-intestinal duct. A steady and significant improvement in the results of treatment was noted in children suffering from necrotising enteritis in the study period. PMID- 2583801 TI - Blood pressure in spontaneously hypertensive rats fed butterfat, corn oil, or fish oil. AB - Dietary fats have been shown to influence blood pressure in humans and animal models of hypertension. The ability of a particular fat to modulate arterial pressure appears to depend on its fatty acid profile rather than its degree of saturation or unsaturation. Little is known about the effects of specific dietary fats of animal origin on blood pressure. We tested the concurrent effects of both calcium and dietary fat on blood pressure development in the spontaneously hypertensive rat. Sixty animals were fed diets containing butterfat, fish oil, or corn oil from 3-26 weeks of age. Each diet among the three oils was further modified to contain either 0.25% or 2.0% of the diet as calcium. All six diets provided 18% of the diet (36% of the calories) as fat. The polyunsaturated-to saturated fat ratio was 0.07, 0.84, and 4.54 for butterfat, fish oil, and corn oil, respectively. Fish oil consumption resulted in lower blood pressures compared with butterfat (p less than 0.036) or corn oil (p less than 0.0009). Similarly, butterfat feeding resulted in lower blood pressures when compared with corn oil (p less than 0.054). Supplementing the diet with calcium decreased blood pressure in both the butterfat and corn oil diets. When butterfat diets were supplemented with calcium, the resulting blood pressures did not differ significantly from those obtained with the two fish oil diets. It is concluded that butterfat, though highly saturated, is associated with less of an increase in the spontaneously hypertensive rat's blood pressure than is corn oil, which is highly unsaturated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583803 TI - Profile of blood pressure in normal school children. AB - A total of 2073 school children between the age group of 5-14 years were examined to define the normal range of auscultatory blood pressure and prevalence of hypertension. An equal number of children in each age, sex and socio-economic group were studied. Mean figures for systolic and diastolic blood pressure with standard deviation and 95th percentile position for each age group were calculated. Systolic and diastolic blood pressure for both sexes had a direct correlation with age, weight and height. Overall prevalence of hypertension was found to be 2.93%. PMID- 2583804 TI - Infant and early childhood mortality in urban slums under ICDS scheme--a prospective study. AB - The infant and early childhood mortality, its causes and associated factors were studied prospectively, in twelve Anganwadi centres, situated in urban slums of Patna from 1st January, 1987 to 31st December, 1987. A strict recording of births and deaths was done by Anganwadi workers, with monthly verifications by authors. The causes of death were established on the basis of clinical and corroborative enquiry from the parents. The birth rate was found to be 29.25, death rate 13.1, infant mortality rate 64.65/1000. Neonatal and post neonatal mortality rates were 49.42/1000 and 15.21/1000, respectively. Mortality in children between 1-3 years (11.3/1000) was higher in comparison to that of 3-6 years (9.1/1000). Low birth weight (25.52%) and perinatal infection (23.52%) were the major causes of infant mortality followed by respiratory infection (11.76) and diarrhea (8.82%). Diarrhea (37.5%), respiratory infection (15.62%) and accidents and burns (12.5%) were major killers in children between 1-6 years. Mortality in males was higher than females in infancy. Risk factors associated with infant mortality included extremes of maternal age (less than 20 and greater than 30 years), multiparity and illiterate mothers. PMID- 2583805 TI - Morbidity pattern in children below three years attending a rural health centre in Haryana. AB - Morbidity pattern of children below three years attending a rural health centre was studied prospectively for one year. All children were first examined by a doctor and the diagnoses made were compiled and analysed. The common morbidity conditions found were pyoderma (23.65%), respiratory infection (21.18%), diarrhea (20.05%), unspecified fever (11.75%), ear infection (6.58%) and eye infection (5.46%). The maximum episodes of morbidity were recorded in summer season (39.22%) followed by rainy (31.36%) and winter season (30.16%). PMID- 2583806 TI - Late hemorrhagic disease of infancy. AB - Over a period of 1 1/2 years, 9 infants ages ranging between 3 weeks and 7 months presented with the syndrome of late hemorrhagic disease related to vitamin K deficiency. All were exclusively breast fed and had not received vitamin K at birth. Four of these had acute intracranial hemorrhage, of which 2 expired and the surviving 2 have residual neurologic handicap. Of the remaining 5 who had skin and mucosal bleeds, all recovered on administration of vitamin K. PMID- 2583807 TI - Retinal hemorrhages in newborn--fetal causative factors. AB - Two hundred and eight alive newborns examined within 2 hours of birth showed 37.50% incidence of retinal hemorrhage (RH). Out of these, 38.59% were full term and 29.17% were preterm. Head circumference had a significant correlation (p less than 0.05) with retinal hemorrhage, while sex of the newborn, birth weight, gestational age and fetal distress showed no significant correlation. Birth injuries especially ocular and periocular injuries showed a significantly higher incidence of retinal hemorrhage (83.33%). PMID- 2583808 TI - Brain stem evoked response audiometry in neonates. AB - Brain stem evoked response audiometry (BERA) was performed in 50 normal full term newborn infants (25 male, 25 female) to generate normative data base for this age group. The stimuli of 30 dB, 40 dB and 80 dB nHL (normal hearing level) intensities were delivered to each subjects. 30 dB stimulus failed to produce clear wave patterns, whereas upto six vertex positive waves were recognised among which waves I, III and V were commonly present. The absolute latencies of waves I and V at 40 dB nJL were 2.54 +/- 0.21 msec and 7.56 +/- 0.26 msec and at 80 dB nHL these were 2.06 +/- 0.15 msec and 7.09 +/- 0.17 msec respectively. I-V interpeak latencies (IPL) were 5.02 +/- 0.13 msec at 40 dB and 5.03 +/- 0.13 at 80 dB nHL. The latencies of waves I and V were decreased with the increase of intensity of stimuli with the rate of 0.012 msec/dB, bit I-V IPL, i.e., central conduction time remained almost constant. There were no statistically significant differences in the brain stem auditory evoked responses between male and female subjects. Brain stem evoked response audiometry is objective and reliable for hearing screening in neonates. PMID- 2583809 TI - Cord blood lipid levels in low birth weight newborns. AB - Cord blood cholesterol, triglyceride and FFA levels were estimated in 73 newborns, subdivided into various gestation weight categories (FTAGA, PTAGA, FTSGA and PTSGA). Cholesterol levels were not influenced by birth weight and gestation. Prematurity and growth retardation caused a significant elevation in triglyceride values. FFA levels were not influenced by prematurity, but growth retardation produced a significant increase. Birth weight and gestational age should be taken into consideration before labelling the newborn as hyperlipidemic. PMID- 2583810 TI - Health status of rural school children. PMID- 2583812 TI - Adult respiratory distress syndrome in a neonate. PMID- 2583811 TI - Disseminated neonatal aspergillosis. PMID- 2583813 TI - Citrullinemia: early diagnosis & successful management of an otherwise lethal disorder. PMID- 2583814 TI - True isolated levocardia with abdominal situs inversus. PMID- 2583815 TI - An unusual foreign body in the esophagus of an infant. PMID- 2583816 TI - Cervical teratoma in newborn. PMID- 2583817 TI - Unusual bone changes and laboratory features in congenital syphilis. PMID- 2583819 TI - Visitors in a pediatric ward. PMID- 2583818 TI - Dermatoglyphics in retinitis pigmentosa. PMID- 2583820 TI - Seasonal variation in birth weight patterns. PMID- 2583821 TI - Dose of verapamil in neonates and young infants. PMID- 2583822 TI - Celiac disease in Indian children. PMID- 2583823 TI - Use of body mass index for assessing the growth status of infants. AB - Growth status of infants measured by weight and height was assessed from birth to 12 months in a randomly selected community from the urban slums of Hyderabad City. Mean birth weight was 2.82 kg. Weight/height indicator of body mass index (BMI) showed a progressive increase till 4th month, followed by more or less a constant figure with a mean value of 1.50 in longitudinal, semi-longitudinal and cross sectional data till one year. Critical limit for BMI at birth for given weight of 2.5 kg was 1.20 and subsequently increased to 1.35. BMI was well correlated with weight and weight for height (%) and least correlated with height. Children with height of 90% or above and birth weight of above 2.5 kg were observed with better growth and better maintenance of weight for height (%) and BMI till 6 months. PMID- 2583824 TI - A study of psychiatrically normal children in a hospital based child guidance clinic. AB - A total of 1330 children who attended a hospital-based child guidance clinic in last three years were studied retrospectively. 7.37% of these were found to have no psychiatric disorder. Epilepsy and scholastic backwardness without any psychiatric disorder, together constituted 70.41% of this group. Children referred to a child guidance clinic require proper assessment to detect psychiatrically normal children who would otherwise receive unnecessary label of psychiatric disorder and treatment. PMID- 2583825 TI - Care of the newborn by traditional birth attendants. AB - The study was carried out in a slum cum resettlement colony (Area-I) and four villages (Area-II) of Delhi. Management of the newborn by the 25 functioning Traditional Birth Attendants (TBA's) who conducted 83.64% deliveries in Area-I and 16.22% in Area-II was studied. Majority of TBA's did not have the concept of washing hands before conducting per vaginum (P/V) examinations or deliveries. Most of the TBA's, i.e., 21 out of 25 used a razor blade to cut the umbilical cord of which 9 used a fresh blade. No TBA left the cord untied. Vigorous patting in upright and also after holding the baby upside down was the commonest (68%) method of neonatal resuscitation. All TBA's massaged and bathed the baby everyday. Majority of the TBA's (18 out of 25) referred the baby to a health agency for immunization though they did not know the exact schedule. PMID- 2583826 TI - Cord and maternal serum IgM in IUGR babies. AB - Due to constraints in conducting specific tests for diagnosis of perinatal infection, the present study was carried out to find out the value of cord serum IgM levels as a screening procedure for intrauterine infection in full term intrauterine growth retarded (IUGR) babies. Thirty five consecutively born full term IUGR singleton babies and their mothers (having weight greater than 40 kg, height greater than 145 cm, Hb 8 g/dl and normal blood pressure) formed the study group. Ten full term singleton babies weighing greater than or equal to 3000 g and their mothers served as controls. In the study population both mean cord serum IgM (26.8 mg/dl) and mean maternal serum IgM (142.42 mg/dl) were raised as compared to the mean cord serum IgM (13.76 mg/dl) and mean maternal serum IgM (100.16 mg/dl) of the control group. However, statistically the rise was significant only between the maternal cord serum IgM levels. But all the same, cord serum IgM levels exceeding 20 mg/dl and 30 mg/dl were found in 51.43 and 22.8% of full term IUGR neonates, respectively whereas among the control neonates only 20.0% had levels exceeding 20 mg/dl and none had levels above 30 mg/dl suggesting possible intrauterine antigenic challenge to perinatal infection in higher proportion of IUGR babies. Cord serum IgM levels were also seen to increase with increase in birth weight. Idiopathic IUGR babies having cord serum IgM levels greater than 30 mg/dl should undergo specific immunological tests and follow up. PMID- 2583827 TI - Upper and lower limb standards in newborn. AB - One thousand live born babies of various gestational ages were studied. Using standard techniques, various limbs anthropometric measurements were taken with a non-stretchable measuring tape. Normal values and S.D. for each gestational week were calculated and their relation with gestational age statistically analysed. All these measurements correlated with gestational age. Foot length correlated best with gestational age amongst all the measurements (r = 0.9399). PMID- 2583828 TI - Maternal and neonatal anthropometric and hematological parameters in Manipuri population. AB - One hundred and sixty five women admitted in the Regional Medical College Hospital, Manipur, for delivery and their newborns were studied for some anthropometric and hematological parameters. The mean weights of mothers and infants were 50.94 +/- 0.86 kg and 2.86 +/- 0.07 kg, respectively. The mean hemoglobin levels were 11.05 +/- 1.57 g/dl in mothers and 15.05 +/- 0.27 g/dl in cord blood. Statistically no correlation existed between hemoglobin levels and between weights of mothers and infants. PMID- 2583829 TI - Septal deviation in neonates. AB - Deviated nasal septum (DNS) is believed to occur in neonates following the trauma of birth processes. The present prospective study was undertaken to evaluate the relationship of intrauterine and parturition processes with neonatal septal dislocations. The neonates were subjected to a series of tests to assess presence and extent of deviated septum within the first 48 hours. A statistically significant correlation was demonstrable between the incidences of septal deviations with intra uterine fetal positions and mode of delivery. PMID- 2583830 TI - Factors responsible for refusal of medical care. PMID- 2583831 TI - Community participation in child health promotional activities at a primary health centre in Haryana. PMID- 2583832 TI - Management of omphalocele with bowel pathology--primary or iatrogenic. PMID- 2583833 TI - Acquired zinc deficiency in an infant resembling acrodermatitis enteropathica. PMID- 2583834 TI - Severe lead intoxication in a family caused by use of residential premises for battery manufacturing. PMID- 2583836 TI - Vaccine transport. PMID- 2583835 TI - Middle fossa arachnoid cysts. PMID- 2583837 TI - Terbutaline in wheezing infants. PMID- 2583838 TI - Acute dapsone poisoning. PMID- 2583839 TI - Hydrothorax complicating peritoneal dialysis. PMID- 2583840 TI - Biocompatibility and safety of cytapheresis. AB - Cytaphereses are safe and can be used routinely like whole blood donations on the premise that standard techniques based on appropriate guidelines and regulations are performed. Before the introduction of a new cell or plasma separator, a thorough clinical investigation is always recommended in order to demonstrate biocompatibility and safety features. In this context cell loss and damage as well as activation of coagulation and complement should be tested primarily. The examination should consist of a direct comparison with an approved system. In addition, it is necessary to repeat periodically on multicenter studies adverse donor reactions such as those already described so that it is possible to recognize even rare side effects. Of special importance are long-term studies of donors undergoing frequent cytaphereses for many years in order to detect relevant immunological changes. On the other hand, harm caused by the plasticizer or cancer due to cancerogenicity of the plastics are only speculative at the moment. PMID- 2583841 TI - The safety of blood component preparation with blood cell separators. AB - Despite initial skepticism following the introduction of cytapheresis with blood cell separators, this technology is now accepted in the field of blood donation. Serious, life-threatening reactions have not been observed and thus could not influence the development, and minor problems can be reduced further on the basis of recommended safety guidelines. Additionally, the continuous registration of side effects is helpful for a complete elimination of undesired reactions. PMID- 2583842 TI - COBE Spectra Apheresis System: designs, protocols and results. AB - The COBE Spectra System will perform all types of apheresis procedures. One of its main procedures is to collect single donor platelets. Because of the unique abilities of this device, the procedures are individualized by the control of several algorithms. Prior to the beginning of the run, a platelet yield is predicted using the entered platelet count. Based upon this information, changes can be made in the operating parameters to optimize the collection. Leuko-poor thrombozytes are produced which can be stored for 5 days. The collect concentration monitor, an on-line device, provides information on the use of thrombocyte concentration and yield, without the use of probes. The future of this system will ensure increased platelet yields with new channel designs or protocol modifications. PMID- 2583843 TI - Collection and transfusion of single donor platelets and their clinical response. AB - The success of transfusing platelet concentrates depends on a variety of factors; those factors are to a certain extent the subject of this paper. The quantity and quality of platelets transfused is discussed in relation to peripheral blood platelet concentration. The data obtained do not yet allow a final conclusion at present, so that further investigations are required. PMID- 2583844 TI - Further results with the COBE Spectra system. Platelet collection using the COBE Spectra. PMID- 2583845 TI - Comparison of plateletapheresis with two cell separators using identical donors. PMID- 2583846 TI - Use of the COBE Spectra System (CSS) for platelet pheresis (PP) and intensive plasma exchange (IPE). PMID- 2583847 TI - Simulated plasma exchange procedures with the COBE Spectra apheresis system using healthy donors. PMID- 2583848 TI - Lymphocytopheresis for killer cell generation and in patients with chronic lymphocytic leukemia: comparison of the COBE 2997 and the COBE Spectra. PMID- 2583849 TI - Fractionation and analysis of allergenicity of allergens from Prosopis juliflora pollen. AB - Prosopis juliflora pollen allergen extract was prepared, and its crude allergen extract was fractionated by Sephadex G-100 gel filtration. Six different fractions were obtained which was confirmed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Protein and carbohydrate content of each fraction were estimated. Fraction E (MW 20,000) showed a 25% carbohydrate concentration. The amino acid analysis indicated that this fraction was rich in glutamic acid and alanine. Antigenicity or allergenicity of fractionated allergens were checked by gel diffusion test, rocket immunoelectrophoresis, skin prick test, and radioallergosorbent test. All these test indicate that fraction E consisted mainly of allergenic molecules (MW 20,000) of P. juliflora pollen. PMID- 2583850 TI - Anti-asthmatic activity of newly synthesized calcium antagonists: 2-n-butyl-1 (N methyl-n-[2-(N',N'-dimethylamino)ethyl]amino) -5,6-methylenedioxy-indene and indane. AB - The anti-asthmatic activity of the newly synthesized methylenedioxyindene (MDI) derivatives, 2-n-butyl-1 (N-methyl-N-[2-(N', N' -dimethylamino)ethyl]amino)-5, 6 methylenedioxy-indene (MDI-C) and -indane (MDI-D), were investigated in vitro and in vivo in guinea pigs. The in vitro pharmacological activity of both derivatives was compared to that of 8-(diethylamino)octyl-3,4, 5-trimethyoxybezoate hydrochloride. All three agents caused a concentration-dependent inhibition of the antigen-induced contraction of sensitized guinea pig tracheal smooth muscle. In histamine and leukotriene D4-induced contractions of guinea pig tracheal smooth muscle, each agent showed clear antagonistic actions. Additionally, all three agents demonstrated potent calcium antagonistic actions via inhibition of guinea pig tracheal smooth muscle contractions caused by CaCl2 in a high potassium and Ca-free medium and by compound 48/80 in a solution of ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid in a contained Ca free medium. MDI-C and MDI-D inhibited the antigen-induced release of histamine and slow reacting substance of anaphylaxis from sensitized guinea pig lung tissue. Lastly, both MDI is clearly inhibited asthmatic respiratory disorders without affecting blood pressure in guinea pigs. PMID- 2583851 TI - Antigen-specific T-cell factors induce isotype-like suppression of mast cell and eosinophil-rich T-cell-dependent inflammation in the intestine of mice infected with Trichinella spiralis. AB - The recent identification of a T-cell-derived antigen-binding molecule (TABM), Trichinella spiralis factor (Tric-F), isolated from culture supernatants of lymphoid cells from mice infected with the intestinal helminth T. spiralis, has led to investigation of the ability of Tric-F to induce a T-cell-dependent feedback circuit that ultimately suppresses the production of other TABMs with similar (isotype-like) features. This form of regulation that has been identified in contact hypersensitivity and in delayed-type hypersensitivity (DTH) responses to tumor cells, was shown not to be antigen-specific but to be DTH-specific. Injection of mice with the TABM called picryl chloride factor (PCl-F) induced suppression of the production of DTH-initiating TABMs of other antigenic specificities. In this study, we report that intravenous injection of mice with Tric-F or PCl-F, 8 days before an oral infection with T. spiralis, induced suppressor cells that inhibited the T-cell-dependent influx into the gut of inflammatory cells, comprising mast cells and eosinophils. Similar results were obtained when the mice were skin sensitized with PCl 8 days prior to a T. spiralis infection, i.e. in a system where TABMs are known to be produced. The phenotype of these suppressor cells was Lyt-1-2+. This suppression preferentially affected the parasite-induced DTH-like response in the gut. In contrast, increased levels of IgA plasma cells in the gut, and worm expulsion were not affected by these treatments. In reciprocal experiments, intravenous injection of Tric-F, or PCl-F, or an oral infection with T. spiralis (that results in the production of TABMs) given 8 days before contact sensitizing mice with PCl, resulted in a suppression of elicitation of cutaneous DTH, as measured by ear swelling. In contrast, pretreatment with anti-dinitrophenyl IgE antibody did not interfere with intestinal inflammation to T. spiralis nor with DTH to PCl. Our results suggest that similar to cutaneous DTH, T. spiralis-specific T-cell factors are involved in the initiation and regulation of the DTH-like mast cell and eosinophil-rich intestinal inflammation that accompanies T. spiralis infections in the gut. Since both Tric-F and PCl-F induce suppression of cellular immune responses in vivo, independent of antigen specificity, it is concluded that Tric-F belongs to the same isotype of TABMs as PCl-F that therefore can be regulated by a non-antigen-specific, isotype-like, T-cell-dependent feedback mechanism. PMID- 2583852 TI - Immunological studies of the glycoprotein allergen Ag-54 (Cla h II) in Cladosporium herbarum with special attention to the carbohydrate and protein moieties. AB - The glycoprotein allergen Ag-54 (Cla h II) isolated from Cladosporium herbarum was split into its carbohydrate and protein moieties by using alkaline borohydride treatment and deglycosylation, respectively. The native Ag-54, the deglycosylated protein and the protein-free carbohydrate moieties were tested for IgE-binding activity by radioallergosorbent test inhibition using selected sera from individuals with C. herbarum allergy. The deglycosylated material had a stronger allergenic activity than the native Ag-54 with all the sera tested. The Ag-54 carbohydrate moieties were not found to possess any IgE-binding activity. The galactoglucomannan part of the carbohydrate moiety was isolated and it was demonstrated to precipitate IgG rabbit antibody. Removal of the galactofuranose units by mild acid hydrolysis did not alter the IgG-binding capacity of the polysaccharide, indicating that galactofuranose was not immunodominant. PMID- 2583853 TI - In vitro proliferation of murine spleen cells. Strain variation of proliferative responses induced by recombinant IL-2. AB - Proliferative responses of normal (not immunized intentionally) spleen cells from inbred mouse strains to human recombinant interleukin 2 (L-2) were studied. It was shown that inbred strains vary in their responses to IL-2. The differences were observed for various doses of IL-2 and at various times after stimulation. Experimental data suggested that the strain differences in the magnitude of proliferative responses may result from an interplay of several interrelated factors such as differences in the frequency of the IL-2-responsive cells, differences in inducibility of the expression of the gene for the alpha-chain of the IL-2R, and genetic control of the responses. The latter was found to be exerted by two independent genes with the dominant alleles determining good responses to IL-2. The magnitude of the responses to IL-2 correlated with the magnitude of responses to concanavalin A, but seemed to have no effect on the interferon production or on the primary response to sheep red blood cells. The described phenomenon may have a practical significance in studies aimed at improving tumor immunotherapy with lymphokine-activated killer cells. PMID- 2583854 TI - Effect of tetrandrine on immunological responses and cardiac transplant rejection in mice. AB - Mice treated with the plant alkaloid tetrandrine have a reduced capacity to mount delayed-type hypersensitivity (DTH) responses. This suppressive effect on DTH was more pronounced when treatment was begun 2 days prior to immunization with sheep erythrocytes. Similar dosage regimens significantly delayed the rejection of cardiac transplants. By contrast, there was significant enhancement of antibody production. These immunomodulatory properties of tetrandrine may account for some of its potential in the treatment of chronic inflammatory diseases, where immunological mechanisms are known to play a major role in pathogenesis. PMID- 2583855 TI - Stability studies of Calvatia cyathiformis basidiospore allergens. AB - Calvatia cyathiformis allergens in unfractionated extract (crude), and in extract sequentially fractionated by gel filtration (GF) and hydrophobic interaction chromatography (HIC) were tested for stability. C. cyathiformis allergen sources (crude, GF, HIC) were sampled immediately (0 h), or incubated at 4, 24 or 37 degrees C and then sampled at 8, 24 or 96 h. Polyacrylamide gel-isoelectric focusing immunoprints revealed 3 allergen(s) groups, or bands (Bds) with respective pI of 3.6-4.6, 6.6 and 9.3. Only Bds 3.6-4.6 were stable at 37 degrees C. At 24 degrees C, Bds 3.6-4.6 persisted to 96 h, Bd 6.6 persisted 24 h, and Bd 9.3 waned in 8 h. At 4 degrees C all 3 allergens in HIC were stable for 8 and 24 h; Bd 9.3 was reduced at 96 h. All allergen activity was labile to low pH conditions except for Bds 3.6-4.6. Proteinase K degraded Bd 9.3 more rapidly than Bd 6.6. Immunoprint patterns corresponded to the stained gels and were consistent among different sources. Bd 9.3 is very labile, but reactive with 63% of sera tested. Since 10-15% of C. cyathiformis reactors bind IgE only to Bd 9.3, this is notable variability, and significant for diagnosis and treatment. PMID- 2583856 TI - Measurement of allergens associated with dust mite allergy. I. Development of sensitive radioimmunoassays for the two groups of Dermatophagoides mite allergens, Der I and Der II. AB - Sensitive radioimmunoassays were developed to measure the two groups of major allergens (Der I and Der II) of Dermatophagoides pteronyssinus and Dermatophagoides farinae, in which radiolabeled protein A served as a general tracer. Glass rods covalently coupled with F(ab')2 fragments of rabbit antiserum IgG were incubated first with mite or house dust extracts, and then with affinity purified rabbit antibodies. The bound allergen-antibody complex was detected with a 125I-labeled protein A. The two Der I allergens, Der p I and Der f I, were measured separately with the use of immunoabsorbed rabbit antibodies directed against species-specific determinants, while the two Der II allergens, Der p II and Der f II, were measured as 'Der II' with the use of antibodies directed against common determinants on both allergens. Each assay demonstrated consistently parallel dilution curves with mite and house dust extracts. The mean intraassay and interassay coefficient of variation for each assay ranged from 4.3 to 7.7% and from 3.6 to 9.0%, respectively. The Der p I and Der f I assays were shown to be highly species-specific so that the ratio of Der p I: Der f I would provide a good index of the distribution of the two mite species in a dust sample. The concentrations of the Der I and Der II allergens in different types of mite extract and dust samples from houses were compared using these assays.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583857 TI - Measurement of allergens associated with dust mite allergy. II. Concentrations of airborne mite allergens (Der I and Der II) in the house. AB - Assays of mite allergens (Der p I, Der f I and Der II) in the air of houses became feasible with the use of a low-noise air sampler and a sensitive radioimmunoassay described previously. The levels of the airborne allergens Der I (Der p I + Der f I) and Der II in the living room of 10 houses during usual domestic life were very low, 29.5 and 6.3 pg/m3, respectively, with a Der I: Der II ratio of 4.7:1. At the time of bedmaking, they greatly increased, about 1,000 fold, to 30,900 and 12,600 pg/m3, respectively, with a Der I: Der II ratio of 2.5:1. The amounts of Der I and Der II in the floor dust of the living room were 2,040 and 2,690 ng/g of fine dust, respectively, with a Der I: Der II ratio of 0.8:1. Der I seemed more prone to become airborne than Der II. PMID- 2583858 TI - A case-control study of diet and breast cancer in Argentina. AB - A case-control study of breast cancer was carried out in La Plata, Argentina, where the incidence of the disease is comparable to the highest rates recorded worldwide. One hundred and fifty incident cases were identified through major hospitals. For each case, a hospital control, matched by age and hospital, and a neighbourhood control, matched by residential area and age, were also chosen. Cases and controls were interviewed to obtain information on past diet, as well as demographic and socio-economic characteristics, reproductive and menstrual history and other potential breast-cancer risk factors. The dietary information was obtained from questions on the consumption of specific food items and information on portion sizes from an earlier study was used to estimate intake of calories and selected nutrients. There was a substantial excess energy intake among cases as compared to both control groups, which was present across all 3 major macronutrients which contribute to total calories. Among the food groups, the consumption of eggs was a risk factor for breast cancer, and whole-milk products and green leafy vegetables were protective. After adjusting for the calorie difference in multivariate statistical analyses of nutrients, fibre and beta-carotene consumption were weakly protective. The results are discussed with reference to possible methodological difficulties and previous studies of diet and breast cancer. PMID- 2583859 TI - IL-1 and IL-6 release by tumor-associated macrophages from human ovarian carcinoma. AB - Our study was designed to investigate the production of interleukin-1 (IL-1) and IL-6 in tumor-associated macrophages (TAM) isolated from ascites (18 cases) or solid (7 cases) human ovarian carcinoma. These are pleiotropic monokines which, in addition to affecting proliferation and differentiation of lymphocytes, act on various targets, including vascular cells and liver, and may therefore be involved in the pathogenesis of certain manifestations of malignancy. IL-1 was measured by the thymocyte co-stimulator assay, under conditions in which IL-6 was inactive, and, in 8 cases, by radioimmunoassay (RIA). IL-6 was measured as hybridoma growth factor (HGF) on the 7TD1 cell line. TAM did not release appreciable levels of IL-1 spontaneously and, upon LPS stimulation, were poor producers of this monokine compared to blood monocytes. In contrast, TAM supernatants contained a high level of HGF in the absence of deliberate stimulation, and exposure to LPS either did not affect or further augmented production of this monokine. HGF activity of TAM supernatants was completely blocked by anti-IL-6 antibodies. Ascites fluid from 8 ovarian-carcinoma patients contained high levels of HGF activity, blocked by anti-IL-6 antibodies. Thus, TAM exhibit a dissociation in their capacity to release the functionally related monokines IL-1 and IL-6. IL-6 produced by TAM may account for the elevation of liver-derived acute-phase proteins associated with malignancy. PMID- 2583860 TI - Expression of the pS2 gene in normal, benign and neoplastic human stomach. AB - The expression of the estrogen-regulated breast-cancer-associated pS2 gene was examined in 75 stomach resections taken from 45 patients. The 600-base pS2 mRNA was found in all of the 47 non-neoplastic samples at varying levels: in the histologically normal group we observed a Poisson-type distribution, whereas 79% of the tissues exhibiting dysplastic features expressed high levels of transcript. Tumour samples expressed relatively lower pS2 mRNA, with only 18% having high levels and 43% with no detectable expression. These differences were not correlated to tumour grading, stage or site. No amplification or rearrangement of the pS2 gene was found. Immunohistochemical analysis of formalin fixed paraffin sections, using a polyclonal antibody against pS2 protein, showed specific staining of both cytoplasm and membrane of epithelial cells in the neck region of antral and body glands as well as in luminal secretions. Immunoreactivity was observed in the sub-nuclear region of foveolar cells, with specialized gland and goblet cells in atrophic gastritis being negative. Heterogeneous but strong focal cytoplasmic staining was seen in tumour cells as well as in dysplastic epithelium. Two gastric cell lines, KATO III and MKN-45, derived from poorly differentiated adenocarcinomas also expressed pS2, whereas 3 other lines from well differentiated parental tumours did not. Genomic analysis revealed a BamHI polymorphism in Kato III cells and in the non-expressing MKN-28 cells. Immunostaining to pS2 protein was also demonstrated in the cytoplasm of KATO III cells, but neither these nor any of 30 tissues examined showed any positivity with a monoclonal antibody (MAb) to estrogen receptor. Our results suggest that pS2 is normally expressed in human stomach, possibly in association with secretory activity, and becomes down-regulated during malignancy. PMID- 2583861 TI - Is chronic sunlight exposure important in accounting for increases in melanoma incidence? AB - Most attempts to relate changes in patterns of sunlight exposure to the rise in incidence of malignant melanoma have concentrated on the positive association between intermittent exposure to sunlight and risk of melanoma. The Western Canada Melanoma Study, however, also detected a significant inverse association between melanoma and chronic or long-term occupational sun exposure in men, with the lowest risk (OR = 0.5) in those with maximum occupational exposure, suggesting that chronic exposure may be protective. Data obtained from Canadian census figures indicated that since 1951 there has been a substantial reduction in the number of males engaged in outdoor occupations in Canadian society. These observations suggest that part of the increase in the incidence of melanoma in low-sunlight areas may be due to a reduction over the past 40 years of the size of this group of individuals "protected" by their exposure to UV light. PMID- 2583862 TI - Correlation of HLA-D/Ii antigen expression in breast carcinoma with local lymphohistiocytic infiltration reveals considerable dysregulation in a subset of tumors. AB - Non-neoplastic mammary glands and 203 carcinomas of the breast were examined immunohistochemically for expression of HLA-DR, -DP, and -DQ molecules and the HLA-D-associated invariant chain (Ii). According to the reaction of normal breast epithelium in the course of chronic inflammation, these antigens were found to be induced in 120 carcinomas. In 106 of these the order was Ii greater than or equal to HLA-DR greater than or equal to HLA-DP greater than or equal to HLA-DQ. The extent of induction of these sequentially expressed antigens correlated with the density of local lymphohistiocytic infiltration (Ii: p = 0.003; HLA-DR: p = 0.0005; HLA-DP: p = 0.0000005; HLA-DQ: p = 0.01). Therefore, Ii/HLA-D antigen expression of carcinoma cells in local association with inflammation was regarded as an adequate reaction. The presence of these antigens in the absence of inflammation was regarded as "inadequate hyper-expression", and was found in 14 cases involving Ii, in 8 involving HLA-DR, and in 1 case each involving -DP and DQ molecules. In contrast, 20 cases expressed minimal/no Ii despite heavy inflammatory infiltration. This "inadequate hypo-expression" was also found in 25 cases involving HLA-DR, in 30 involving -DP and in 40 involving -DQ determinants. Combining the 2 variants showed that at least 54 cases (26.6%) were characterized as being dysregulated. "Adequate vs. inadequate Ii/HLA-D antigen expression" did not correlate with tumor grading and might therefore be an independent parameter. PMID- 2583863 TI - Urinary excretion of N-nitrosamino acids and nitrate by inhabitants of high- and low-risk areas for stomach cancer in Poland. AB - Urine samples were collected from 96 inhabitants of a high-risk rural area and a low-risk urban area for stomach cancer in Poland, according to the following protocol: (1) when they were undosed; (2) after ingestion of proline 3 times a day; and (3) after ingestion of proline together with vitamin C 3 times a day. The samples were analyzed for N-nitrosamino acids and nitrates, as indices of exposure to preformed and endogenously formed N-nitrosamines. The median values of N-nitrosoproline (NPRO) and N-nitrosothiazolidine 4-carboxylic acid (NTCA) excreted in the urine of undosed subjects were not different between the two areas; but N-nitrososarcosine and 3-(N-nitroso-N-methylamino)propionic acid levels were 3- to 4-fold higher in subjects of the high-risk area. After intake of proline, the NPRO level increased (p less than 0.02) only in subjects in the high-risk area; intake of vitamin C tended to inhibit this increase in NPRO and lowered the levels of other nitrosamino acids. The urinary level of nitrates was 1.4-fold, but significantly higher among subjects in the high-risk area than among those in the low-risk area; nitrate levels were not correlated with the amounts of cured meat or types of vegetables consumed. Urinary nitrate levels and excretion of NPRO, NTCA and the sum of all nitrosamino acids analyzed showed positive, though modest, correlations. These results indicate a higher potential for endogenous nitrosamine formation, possibly by intragastric nitrosation among subjects in the high-risk rural area. PMID- 2583864 TI - Frequent clonal chromosomal changes in human non-malignant tumors. AB - A cytogenetic analysis has been performed on 109 non-malignant human solid tumors of various histological types after short-term culture. These tumors were derived from epithelial, mesenchymal, embryonal and neurogenic tissues. The chromosome count was in the diploid range in virtually all specimens. Clonal chromosomal changes were found in 37% of tumors: 20% had numerical deviations, 12% structural rearrangements, and 5% both karyotypic alterations. Chromosome 7 was most frequently involved in 25% of abnormal specimens. Our results suggest that chromosomal changes contribute to non-malignant tumorigenesis and that their analysis may provide information about the genetic events which shift benign tumor cells to malignant behavior. PMID- 2583865 TI - Risk of cancer in women receiving hormone replacement therapy. AB - Cancer risk following treatment with non-contraceptive estrogens was studied in a population-based cohort of 23,244 women. Complete follow-up for an average of 6.7 years revealed 1,087 incident cancers versus 962.5 expected (relative risk/RR/ = 1.13; 95% confidence interval 1.10-1.20). We confirmed the recent findings of a more detailed analysis of the same cohort, based on a 1-year shorter follow-up period, namely: a markedly increased risk of endometrial cancer (RR = 1.8; 1.5 2.1), notably in women receiving potent estrogens, i.e., conjugated estrogens or estradiol (RR = 2.0; 1.6-2.4), and a slightly increased risk of breast cancer (RR = 1.1; 1.0-1.2). A slightly decreased risk of invasive cervical cancer (RR = 0.8; 0.5-1.2) is most likely due to more frequent smear taking than in the background population. There was no increase in the risk of cancer of ovary (RR = 1.0; 0.8 1.2), pancreas (RR = 0.8; 0.5-1.2), large bowel (RR = 1.0; 0.8-1.2) or kidney (RR = 1.0; 0.7-1.4). The risk of developing cancer in liver or biliary tract was lower than expected (RR = 0.4; 0.2-0.7), particularly in women who had used potent estrogens (RR = 0.3; 0.1-0.6), an unexpected finding which warrants further studies. Increased risks of malignant melanoma (RR = 1.5; 1.0-2.1) and lung cancer (RR = 1.3; 0.9-1.7) need cautious interpretation because of their low magnitude, the absence of a biological gradient when subgroups were analyzed and the slightly higher prevalence of smokers in the cohort than in the background population. PMID- 2583866 TI - Monoclonal antibody against human squamous-cell-carcinoma-associated antigen. AB - Mouse monoclonal antibody (MAb) 3F8E3 (IgG3k) was developed against the head and neck cancer cell line LICR-LON-HN2. Subjected to indirect immunofluorescence, the MAb reacted exclusively with SCC cell lines and showed no reactivity with normal or transformed mouse and human non-SCC cell lines and hematopoietic cell lines. The radiolabelled MAb showed an affinity constant of 1.8 x 10(8) M-1 with HN2 cells and identified 2.07 x 10(4) sites/cell by Scatchard analysis. It identified 2 peptides from membrane extracts of HN2 cells by Western blotting. Avidin-biotin complexed immunoperoxidase staining on cryostat sections of tumors from various tissues revealed that 3F8E3 reacted mainly with the membrane antigens of well differentiated SCC cells of oral cavity, larynx, esophagus, lung, uterine cervix, metastatic nodes of patients with oral cancer, and dysplastic cells in oral leukoplakia. The MAb did not react with poorly differentiated cells of Ca esophagus, adenocarcinoma of breast, stomach and colon, renal-cell carcinoma and soft-tissue sarcoma. PMID- 2583867 TI - Staurosporine stimulates expression of the urokinase-type (u-PA) plasminogen activator in LLC-PK1 cells. AB - In LLC-PK1 porcine epithelial cells, the urokinase-type plasminogen activator (u PA) mRNA and protein can be induced either by stimulation of the protein kinase C (PKC) pathway using a tumor promoter (PMA) or by stimulation of the protein kinase A (PKA) pathway with calcitonin (SCT). By contrast, addition of 10(-7) M staurosporine, an inhibitor of PKC, to LLC-PK1 cells also stimulated urokinase production. In contrast to the in vitro situation (where staurosporine inhibited PKC activity), in the cell-culture system the microbial agent caused an early translocation of PKC and inhibited PKA. Addition of staurosporine together with PMA or with SCT further increased urokinase mRNA and protein synthesis. Maximal stimulation was obtained when all 3 agents were added together. We thus assume that in LLC-PK1 cells the PKA and PKC signal-transferring pathways can function independently. PMID- 2583869 TI - Phenotypic and cytogenetic characterization of a cell line derived from primary prostatic carcinoma. AB - A new cell line, PPC-I, has been established from a specimen obtained from a patient with a poorly differentiated adenocarcinoma of the prostate. This is the first line of its type derived from a primary prostatic tumor site. PPC-I cells have become immortalized in culture, exhibit transformation parameters including relaxed growth factor requirements and anchorage-independent growth, and are highly tumorigenic in nude mice. Cytogenetic studies by G-banding revealed a grossly abnormal karyotype, with a modal chromosome number of 84, multiple marker chromosomes including both homogeneously staining regions and double minutes and clonal loss of chromosomes 3, 5, 10, 15 and Y. PMID- 2583868 TI - Unique patterns of brain metastasis produced by different human carcinomas in athymic nude mice. AB - The purpose of this study was to develop an in vivo model to study the growth pattern and biological behavior of brain metastases produced by different human carcinomas. To do so, human tumor cells from 8 different carcinomas of the colon, breast, kidney and lung were injected into athymic nude mice either by a direct intracerebral route or into the internal carotid artery. All carcinoma cells invaded through the blood-brain barrier and produced progressively growing lesions in the brain parenchyma. Unique patterns of growth were discernible among the carcinomas. Human colon carcinomas produced multiple lesions that spread by extension. Lung carcinoma cells produced widespread lesions throughout the brain. A very high degree of vascularization was associated with lesions produced by renal-cell carcinoma. The influence of estrogen on the growth of estrogen receptor-positive human breast carcinoma cells was well demonstrated in this model. We conclude that the athymic nude mouse can be a useful model for studies of the biology and perhaps therapy of brain metastases produced by human carcinoma cells. PMID- 2583870 TI - Clustering of discrete cell properties essential for tumorigenicity and metastasis. I. Studies of Syrian hamster embryo fibroblasts spontaneously transformed in vitro. AB - The expression of two discrete cell properties related to the host natural effector mechanisms, i.e., resistance to damage by H2O2, a cytotoxic product of activated macrophages, and the ability to secrete PGE, which inhibits NK-cell cytotoxicity, has been examined in parental Syrian hamster embryo cells spontaneously transformed in vitro (STHE strain) and in 18 in vivo selected sublines. In all cell variants, resistance to H2O2 and PGE-releasing activity were either both expressed, or not expressed at all. Parental STHE cells and 5 variants selected in vivo, which were equally highly susceptible to H2O2-induced damage, did not release any detectable amount of PGE upon contact with NK cells. In contrast, 13 other STHE variants selected in vivo and characterized by their resistance to H2O2, all released PGE upon contact with NK cells. Thus, these two biochemically unrelated cell phenotypic characteristics are likely to be either simultaneously selected in vivo, or united in cluster which pre-exist or appear in rare cell variants of the parental cell population in the conditions of in vivo natural selection pressure. PMID- 2583871 TI - Paradoxical effects of tumour necrosis factor in experimental ovarian cancer. AB - Recombinant human tumour necrosis factor (rhTNF) had anti-tumour activity against 2 of 3 human ovarian cancer xenografts growing intraperitoneally (i.p.) in nude mice, producing a moderate (2- to 3-fold) increase in mouse survival time. rhTNF therapy caused a marked influx of polymorphonuclear neutrophils into the peritoneal cavity during the first few days of daily therapy. This was accompanied by a decrease in the number of peritoneal macrophages and lymphocytes. rhTNF also caused an increase in peripheral blood neutrophils. With continuation of daily therapy, the peritoneal neutrophil influx diminished, with restoration of the macrophage and lymphocyte populations. After 2 to 3 weeks there was a small but significant increase in peritoneal Thy 1.2+ cells. In the peripheral blood, the neutrophilia was less marked than at the start of therapy. Mild myelosuppression was indicated by significant falls in haemoglobin and platelet counts. Within 24 hr of the start of therapy in the 2 responsive xenografts (HU and LA) tumour clumps in the peritoneum were surrounded by host inflammatory cells, and tumours fixed to the omentum were infiltrated by neutrophils and mononuclear cells. In both instances necrosis was evident by 4 to 7 days. The third xenograft (OS) grew although the rhTNF therapy induced the same inflammatory changes in the peritoneum. In contrast to its positive effect on the survival of tumour-bearing mice, rhTNF promoted the adhesion of tumour cells to the peritoneum and their establishment as tumour nodules below the mesothelial surface. This phenomenon was seen in all 3 xenografts including the OS xenograft which did not respond in any other way to rhTNF therapy. PMID- 2583873 TI - Recent endometrial cancer trends in Connecticut and prescriptions for estrogen replacement therapy. PMID- 2583874 TI - Urinary estrogens and male-to-female breast cancer ratios. PMID- 2583872 TI - Effect of polarity and differentiation on antibody localization in multicellular tumour spheroid and xenograft models and its potential importance for in vivo immunotargeting. AB - Two monoclonal antibodies (MAbs) AUAI and HMFGI recognize antigens located on different membrane domains of polarized epithelial cells. We have assessed the accessibility of these antigens in multicellular tumour spheroids produced in culture using a well-polarized (HRA-19) and a non-polarized cell line (LoVo) of human large-bowel carcinoma origin. Multicellular spheroids of HRA-19 cells develop polarity, so that the membrane which is in contact with the culture medium (apical) becomes antigenically distinct from the membrane facing the centre of the spheroids (basolateral). This was confirmed by immunostaining sections of spheroids with 2 MAbs, AUAI and HMFGI. AUAI recognizes an antigen located exclusively on the basolateral membranes of polarized epithelial cells, and stained only internal membranes in spheroid sections. Conversely HMFGI, which recognizes an antigen located on the apical membranes, stained only the periphery of the spheroids. These 2MAbs were then radiolabelled with 125I and incubated with live spheroids for 4 hr at 37 degrees C. Autoradiographs of spheroid sections showed a marked difference between the 2 MAbs. 125I-HMFGI-radioantibody localized exclusively on the spheroid surface in a pattern identical to the in vitro immunostaining pattern, while 125I-AUAI radioantibody showed no binding in spite of the uniform presence of antigen on all tumour cells basolaterally. This appeared to be the result of the inaccessibility of basolateral antigenic sites in well-polarized epithelial cells because of the tight junctions connecting these cells at their apical surfaces. In contrast to the HRA-19 cell line LoVo, spheroids do not develop polarity; as a result, when stained with AUAI, variable antigenic expression all over the cell surface was seen. Autoradiographs of these spheroids showed 125I-AUAI binding with a penetration to a depth of about 1-3 cells, while HMFGI which shows no reactivity with this cell line in vitro, did not bind. This phenomenon was further investigated in xenografts of the HRA-19 cell line. It was shown that in a well-differentiated adenocarcinoma where the tumour cells forming acini are arranged in a polarized fashion, the luminal antigenic sites may be inaccessible to the injected MAb. The striking differences in binding of MAbs on polarized and unpolarized tumours indicate the importance of cell polarization and exact location of antigenic sites for in vivo immunotargeting. PMID- 2583875 TI - Variations of sotalol kinetics in renal insufficiency. AB - Decreased elimination of sotalol (160 mg) is found in patients with renal insufficiency. Simulation of plasma concentrations at steady-state exhibits moderately higher concentrations when creatinine clearance is between 10 and 30 ml/min and very high plasma concentrations when creatinine clearance is less than 10 ml/min suggesting, if treatment is absolutely necessary, monitoring in these cases and the reduction of the dose in major renal insufficiency. PMID- 2583876 TI - Differential effect of type I and type II diabetes mellitus on serum ampicillin levels. AB - Ampicillin elimination was studied in 10 poorly controlled, 6 well controlled type I and 14 poorly controlled type II diabetic patients. Two groups of age matched healthy volunteers served as controls. After oral administration of ampicillin (500 mg), the poorly controlled type I diabetics had significantly lower serum concentration of the drug when compared to their corresponding healthy controls. The elimination half-life (t1/2) remained unaltered. Their creatinine clearance rate and urinary excretion of the drug were significantly reduced. There was no difference in these parameters between well controlled diabetics and healthy volunteers. The bioavailability data calculated from the urinary recovery of the drug, after oral and i.v. administration, suggested reduced oral absorption in poorly controlled type I diabetic patients. Ampicillin kinetics data of poorly controlled type II diabetic patients were not significantly different from that of the control group. Serum ampicillin levels and urinary excretion of the drug were similar in these groups. It is concluded that serum ampicillin level may be lower in poorly controlled type I diabetics which may be due to reduced absorption of the orally administered drug. PMID- 2583877 TI - Effect of age and renal function on gentamicin pharmacokinetic parameters. AB - The effect of age and renal function on gentamicin pharmacokinetic parameters were studied in 125 patients with various degrees of renal function. Patients were grouped according to age. Group 1 ranged from 18-40 years (46 patients), group 2 ranged from 41-64 years (53 patients) and group 3 ranged from 65-92 years (26 patients). Elimination rate constant (K) were 0.28 +/- 0.01 h-1 (mean +/- SEM), 0.23 +/- 0.02 h-1, and 0.16 +/- 0.01 h-1 for groups 1, 2 and 3, respectively. Total body clearance (Clt) were 86.21 +/- 5.0 ml/min, 62.41 +/- 4.36 ml/min, and 46.08 +/- 3.89 ml/min, for group 1, 2 and 3, respectively. No significant differences were found between groups with respect to apparent volume of distribution. There was a significant decrease in creatinine clearance (Clcr) with increase in age. Linear regression analysis revealed good correlations between age of the patients and K (r = 0.4132, p less than 0.05), between age and Clt (r = 0.3999, p less than 0.05) and between age and Clcr (r = 0.5241, p less than 0.05). However, poor correlations between age and apparent volume of distribution and between age and serum creatinine concentration were obtained. Significant relationships were also obtained between the composite parameters Clt/age and K/age vs Clcr (r = 0.7064, p less than 0.001, and r = 0.7200, p less than 0.001, respectively). On the other hand, no significant relations were found between K/Clcr and Clt/Clcr vs age of the patients. These findings suggest that the elimination of gentamicin is independent of age of the patient but is highly dependent on renal function. PMID- 2583878 TI - Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. AB - The pharmacokinetic and pharmacodynamic studies of four different brands of propranolol (Inderal, Ciplar, Corbeta and Propal) were carried out after single and multiple dosing on six normal adult healthy volunteers in a randomized crossover fashion to determine any inter-brand variations in bioavailability and pharmacodynamic effects. No significant difference was observed in any of the pharmacokinetic and pharmacodynamic parameters of four different brands of propranolol studied. PMID- 2583879 TI - A critical theory of medical discourse: how patients and health professionals deal with social problems. AB - Criticism of social context does not generally appear in medical encounters. When contextual issues arise in medical discourse, messages of ideology and social control may become apparent, usually without the conscious awareness of the participants. By easing the physical or psychological impact of contextual difficulties, or by encouraging patients' conformity to mainstream expectations of desirable behavior, encounters with doctors can help win patients' consent to troubling social conditions. Seen in this light, doctor-patient encounters become micropolitical situations that do not typically encourage explicit statements or actions by health professionals to change contextual sources of their patients' difficulties. A critical theory influenced by structuralism suggests that the surface meanings of signs in medical discourse prove less important than their structural relationships. In addition, a theoretical approach adopting elements of post-structuralism and Marxist literary criticism emphasizes the marginal, absent, or excluded elements of medical discourse. Contextual features that shape a text include social class, sex, age, and race. Through the underlying structure of medical discourse, contextual problems are expressed, marginalized, and managed. PMID- 2583880 TI - Proletarianization or restratification of the medical profession? The case of obstetrics. AB - Professional dominance, autonomy, and control have been consistently emphasized in theories of the medical profession. Recently, however, the professional hegemony that physicians have enjoyed is increasingly being questioned in the light of profound changes that are taking place in the organization of health care in the United States. Debates about the implications of the power of medicine and the means by which it is maintained are being replaced by attempts to understand professional decline. Proletarianization (McKinlay and colleagues) and restratification theory (Freidson) are two prominent and competing predictions for the future of the medical profession. Taking obstetrics as a critical case, this article considers the relative ability of these theories to elucidate the changing organization of maternity care in one state and presents a case study of patient care in one hospital. It suggests a disjuncture between obstetricians' inability to protect their interests as a corporate body and their relative ability to control the organization of everyday medical work. It is concluded that more theoretical clarity is needed on professional behaviors at the macro and micro levels. PMID- 2583881 TI - Escalation of the nurse-physician conflict: registered care technologists and the economic crisis. AB - Rivalry between nurses and physicians has been escalating in recent years. The American Medical Association's (AMA's) recent proposal to deal with the nursing shortage by introducing a non-nurse bedside care technician to be called a registered care technologist has met with strong opposition from the American Nurses' Association (ANA). This article suggests that limiting the analysis of this debate to changes taking place within the health sector is problematic. The determining constraints are not endogenous to the health sector, but are located in the broader macroeconomic context. The object, herein, is to locate the AMA's proposal and the ANA's response in the light of the macroeconomic crisis that is forcing the U.S. economy, including the health sector, to restructure. This restructuring generates increasing rivalry and conflict as firms and workers vie to consolidate, and where possible, to expand their relative power in the face of generally declining and qualitatively changing circumstances. PMID- 2583882 TI - Privatization in French health politics: few projects and little outcome. AB - The author presents the main features of the organization of the French health care system, revealing an important mixture of public and private actors and institutions and a large number of political restraints that oppose resistance to privatization. In spite of traditional references to "liberal medicine" and recurrent debates opposing public and private intervention, neither the doctors nor the political decision makers have really supported the few projects that have been proposed for privatization or liberalization of health care. On the contrary, the cost-control policy introduced growing State intervention and new management methods into the health care sector, whose actors were not used to it. The privatization and liberalization debates appear as a rhetoric necessary to accommodate these difficult changes. PMID- 2583883 TI - Doctors and detailers: therapeutic education or pharmaceutical promotion? AB - Pharmaceutical companies in industrialized countries generally view detailers as the most crucial element in the promotion of their products, with the result that over 50 percent of expenditures on promotion are devoted to detailers. Publicly the companies make claims for the scientific knowledge of detailers and for their role in passing on information to physicians, but the main purpose of detailers is to sell their company's products. This emphasis on sales is evident from statements of detailers themselves, from advertisements for detailers, from company documents, and by looking at the groups of physicians that companies specially target for visits by detailers. A variety of explanations are offered as to why physicians see detailers, but on examination none of the reasons is justifiable. Studies from a number of industrialized countries have shown that over 90 percent of physicians see detailers and a substantial percentage rely heavily on detailers as sources of information about therapeutics. Detailers are highly successful in altering physicians' prescribing habits, but almost all the literature available shows that the more reliant doctors are on commercial sources of information, the less appropriate they are as prescribers. Widespread use of DES (diethylstilbestrol) and the Dalkon Shield was encouraged by detailers. Although detailers have received the endorsement of both physicians' groups and government bodies, seeing detailers is detrimental to the practice of good medicine, and the best interests of doctors and their patients would be served if physicians had nothing further to do with detailers. PMID- 2583884 TI - Gender, work control, and stress: a theoretical discussion and an empirical test. AB - Within the field of occupational stress research the theoretical orientation, the research instruments, and the populations studied have largely been standardized on and restricted to male subjects. This article discusses the threats that single-sex studies pose to the valid assessment of the health effects of working life. Following this critique, an empirical examination of the differential distribution of work control is examined within a random sample (n = 13,203) of Swedish working males and females. Results indicate that even in a socially progressive society the labor force continues to be highly sex-segregated. Males, as a group, were found to have access to a larger and more diverse set of jobs than do females, as a group. Work control was found to be consistently higher among men than among women. The highest level of control was found among white collar men in male-segregated jobs, while the lowest was found among blue-collar women in male-segregated jobs. It was notable that men had a higher level of control than women even in jobs that are traditionally considered "women's work." The implications of these findings are discussed in terms of future directions in the psychosocial work environment field. PMID- 2583885 TI - Prevention and rehabilitation of osteoporosis program: exercise and osteoporosis. AB - Osteoporosis is a common crippling bone disease affecting post-menopausal and elderly women. It results in fractures, spinal deformity and chronic pain leading to decreased mobility and functional disability. A preventive program in Toronto, described in this article, aims to prevent bone loss and maximise the functional capacity of osteoporotic patients through a program with educational, social and exercise components. Evaluation of the program, also reported here, showed that 80 per cent of patients complied with the requirements of the exercise program and that those who exercised reported improvement in general well being, stamina, mobility and pain tolerance. The exercise group also showed a significant improvement in VO 2 max (p less than 0.001) and bone mass (p less than 0.02) after one year of exercise. None of the patients developed fracture as a direct result of the exercise. The exercise prescribed for osteoporosis is safe and beneficial. The program is a social success. PMID- 2583886 TI - Getting in touch with pictures and words: educational strategies for the blind. AB - Tactual processing of information is of much more significance for blind than sighted persons, for whom it is a less dominant channel of communication. However, it has received much less attention than verbal or visual processing of information. In this article, the main outcomes of a series of experiments with congenitally blind children are described, with their performance on a series of spatial reasoning and shape recognition tasks compared to that of blindfolded, partially sighted controls. Results suggest that congenitally blind subjects perform as well as, if not better than, blindfolded subjects on simple 2 dimensional tactual processing tasks, but less well on more complex tasks requiring them to store, compare and label objects. This is thought to reflect their poorer sensory coding abilities and their more limited experience of pictures and representations of objects. While other work suggests that blind children can be trained to enhance these skills, the fact that they appear to utilise different learning strategies should be taken into consideration in educational practice and explored further in future research. PMID- 2583887 TI - The biological significance of the Mongolian spot. PMID- 2583888 TI - Brittle nails. PMID- 2583889 TI - Markers and relative risk in a German population for developing malignant melanoma. AB - The relationship between cutaneous malignant melanoma (MM) and possible risk factors was assessed in a case-controlled study. Two hundred patients and 200 non melanoma controls of German origin matched for age and sex were interviewed and examined for pigmented moles and pigmentation characteristics. In patients with MM significantly more melanocytic nevi greater than or equal to 2 mm (MCN) were found (mean, 53 MCN) compared to control cases (mean, 18 MCN). For persons with greater than 60 MCN the relative risk (RR) for developing MM increased 15 times compared to less than or equal to 10 MCN. Additional independent markers for an increased risk were presence of atypical MCN (RR = 7 vs. none) found in 45% of patients and in 5% of the control group, moderate to large numbers of actinic lentigines (RR = 6.2 vs. none), and lack of tanning as well as a tendency to sunburn (skin type I; RR = 2.2 vs skin type IV) No significant correlation was found between the relative risk for MM and hair color, eye color, duration of free time sun exposure and number of sunburns. Individuals with permanent outdoor profession and sun exposure, however, showed a clearly increased relative risk for developing MM. PMID- 2583890 TI - What lichen planus patients die of. A retrospective study. AB - The causes of death of 50 patients who had had lichen planus have been investigated and compared with those of 50 patients with psoriasis and with those of the general population. Patients with lichen planus were as old as those with psoriasis and in the general population at the time of death, but the diseases causing death differed. Malignant tumors, particularly those of the gut and the bladder, and malignant hemopathies exceeded the expected prevalence. In addition, autoimmune diseases were more common than in patients with psoriasis and in the general population. Multiple sclerosis and primitive pulmonary fibrosis have never been described before in patients with lichen planus. PMID- 2583892 TI - Lichen planus and ulcerative colitis--is there a relationship? PMID- 2583891 TI - Reproductive factors and melanoma of the skin among women. AB - A higher risk of reproductive system disorders, (which include benign tumors, endometriosis, dilation and curettage, hysterectomy, and other disorders requiring gynecologic biopsies) exist among women with cutaneous melanoma as compared to women with skin cancers: The odds ratio (OR) is 3.2, 95% confidence limits (1.0, 10.1), p = 0.049; as compared to a random sample of women with no melanoma or skin cancers, the OR is 3.9, 95% confidence limits (1.2, 12.4), p = 0.021. Confirming the observations of others, the authors found that melanoma was associated with red hair. The data also confirmed the finding that melanoma is associated with significantly fewer pregnancies. The mean numbers of pregnancies in the melanoma group is 1.83 +/- 1.6 (mean and standard deviation) compared to 2.99 +/- 1.9 in the skin cancer group and 2.93 +/- 1.9 in the random sample (p less than or equal to 0.05). PMID- 2583893 TI - Dermal malignant melanoma developing from a nevus of Ota. PMID- 2583895 TI - Verrucous sarcoidosis simulating hypertrophic lichen planus. PMID- 2583894 TI - A pigmentary purpuric eruption associated with an unusual platelet dysfunction. PMID- 2583896 TI - Malignancy in lichen planus. PMID- 2583897 TI - Vitiligo therapy with oral and topical phenylalanine with UVA exposure. AB - The administration of phenylalanine (Phe) combined with UVA exposure was found to be effective in treating vitiligo. Twenty-one patients with vitiligo were divided in two groups: eleven patients were treated with oral L-Phe in a dose of 100 mg/kg body weight and with UVA exposure and ten patients were treated with oral L Phe in a dose of 100 mg/kg body weight and with UVA exposure. In addition, in the second group, a cream containing 10% L-Phe was applied to the vitiliginous areas. The best results occurred in the second group. No side effects were found in either group. PMID- 2583898 TI - Impetigo herpetiformis: response to steroids and etretinate. PMID- 2583899 TI - Cutaneous Crohn's disease: treatment with intralesional steroids. PMID- 2583900 TI - Adenoid (pseudoglandular) squamous cell carcinoma at the base of cutaneous horn. PMID- 2583901 TI - Nail pigmentation resulting from selenium sulfide and copper. PMID- 2583902 TI - AIDS, Kaposi's sarcoma, and the gay population. The germ or the terrain? PMID- 2583903 TI - Risk factors for basal cell carcinoma. AB - Completed questionnaires regarding suspected risk factors for basal cell carcinoma (BCC) were completed by 538 basal cell carcinoma patients and 738 age-, sex-, and location-matched controls in Saskatchewan. Significant risk factors were identified using chi2 analyses. Relative risks were subsequently computed. The following relative risks were identified: occupation of farming, 1.29; prominent freckles in childhood, 1.23; family history of skin cancer, 1.22; sunburn, 1.19; Irish, Scottish, Welsh mother, 1.19; light skin color, 1.18; red/blond hair color, 1.16; and working outdoors more than 3 hours/day in winter, 1.13: The average age of cases of BCC with a family history of skin cancer was significantly lower than cases of BCC with no family history of skin cancer (63.86 vs. 67.02 years, p = 0.018). No association was noted between BCC and psoriasis. PMID- 2583904 TI - Unilateral dermatomal superficial telangiectasia overlapping Becker's melanosis. PMID- 2583905 TI - Allergic granulomatosis and angiitis of Churg-Strauss. Case report in a patient with antibodies to human immunodeficiency virus and hepatitis B virus. PMID- 2583906 TI - Radiation-induced erythema multiforme. An unusual presentation with elastic tissue phagocytosis. PMID- 2583907 TI - Diflucortolone valerate ointment with and without occlusion in lichen simplex chronicus. PMID- 2583908 TI - PUVA treatment inhibits nonimmunologic immediate contact reactions to benzoic acid and methyl nicotinate. AB - The effect of trioxsalen bath PUVA therapy on nonimmunologic immediate contact reactions (NIICRs) induced by benzoic acid (BA) and methyl nicotinate (MN) was studied in 12 dermatologic patients. One half of the back skin was covered with a cloth before each of ten irradiations on subsequent days. Four concentrations of each test substance were applied to the PUVA-exposed and nonexposed areas before any irradiation and after the 1st, 5th, and 10th PUVA treatment. Erythema and edema reactions were observed visually 40 minutes after BA and MN application, and changes in the skin blood flow were monitored using laser Doppler flowmetry (LDF). PUVA therapy suppressed the NIICRs in all concentrations of BA and MN on the PUVA-exposed area and occasionally on the nonexposed test sites. The suppressive effect was intesified during therapy. PMID- 2583909 TI - Dermal leishmaniasis and rifampicin. AB - In an uncontrolled study, the effectiveness of rifampicin was assessed in cutaneous leishmaniasis. Twelve of 15 patients (80%) showed good response. The treatment ranged from 2 to 12 weeks. Tolerance of the drug was excellent and apart from red discolouration of the urine, no other side effects were encountered. Rifampicin appears to have a place in the management of cutaneous leishmaniasis. PMID- 2583910 TI - Dermatitis herpetiformis associated with myasthenia gravis. PMID- 2583912 TI - The possible role of routine skin cancer screening in the military. PMID- 2583911 TI - Cutaneous leishmaniasis in Belize. PMID- 2583913 TI - Mode of delivery in Ehlers-Danlos syndrome: a reappraisal of the current approach. PMID- 2583914 TI - Fatty acid composition in serum lipids and adipose tissue in severe obesity before and after six weeks of weight loss. AB - Fatty acid composition was studied in 25 grossly obese patients (mean weight 116 +/- 21 (s.d.) kg) before and after 6 weeks of treatment with a combined program consisting of diet, behavioral modification and light exercise. Data were compared with results from nonobese controls. In obese patients the most marked differences were reduced relative contents of linoleic acid in serum triglycerides (P less than 0.001), cholesterol esters (P less than 0.05) and phospholipids (P less than 0.001). Linolenic acid was reduced in serum triglycerides (P less than 0.001) and in cholesterol esters (P less than 0.01). There were reciprocal increases in palmitic and palmitoleic acid (P less than 0.05) in these two serum lipid fractions. In adipose tissue of obese patients only minor differences were found in palmitoleic acid, which was increased, and in the saturated fatty acids with 14, 16 and 18 carbon atoms which were decreased. Weight loss (600 kcal/day for 6 weeks, P/S ratio about 0.5) did not affect adipose tissue fatty acid composition, but resulted in reductions of linoleic acid content in cholesterol esters and phospholipids, with reciprocal increases of palmitic and arachidonic acid in these fractions. Our results suggest that obese patients have low essential fatty acids content in their circulating plasma lipids already in a weight stable phase. Therefore it may be argued that in the development of long-term dietary restriction programs attention should be paid to the quality of the dietary fat. PMID- 2583915 TI - Caloric intake and activity levels are related in young children. AB - In this study the relationship between caloric intake and activity levels was examined in forty-three 18-month-old children. Caloric consumption was measured during a laboratory meal, and activity levels were assessed using an ambulatory monitor over a 24-hour period. Caloric intake was found to be significantly correlated with activity levels, such that children with a high caloric intake tended to have lower activity levels. This finding suggests that two risk factors influencing the development of obesity, caloric intake and physical activity levels, are likely to occur together in a subset of young children. A possible mechanism underlying this association is discussed. PMID- 2583916 TI - Weight change underway and in port in the American Navy. AB - The introduction of strict weight control guidelines in the American Navy has drawn attention to a theory that obese sailors lose weight more readily at sea than ashore. I tested this hypothesis retrospectively over a 13 month period on a large American naval vessel, using data on 40 obese men who were weighed weekly as part of a mandatory health and physical readiness program. Included in the study period were both a 25 week deployment and a 29 week extended in port period. Ten subjects were enrolled for the entire 13 months, and their mean in port and underway weight changes were compared using a paired t test. Regression analysis was also performed comparing time underway or in port with net weight change for all subjects. The 10 men enrolled for 13 months had a mean weight loss of 6.6 kg during the underway period and a mean weight gain of 4.3 kg during the in port period (P less than 0.005). Number of weeks underway and number of weeks in port were found to correlate with number of kilograms lost and gained, respectively (P less than 0.005). These data suggest that men who have strong incentives to lose weight do so more effectively at sea than after returning from sea. PMID- 2583917 TI - Effects of chronic low doses of d-fenfluramine on weight gain and calorie intake, brown adipose tissue thermogenic parameters and brain neurotransmitter content in rats fed chow or palatable diets. AB - Male black-hooded rats of original age 3 months were maintained on either a standard laboratory chow diet or a palatable diet (32 animals in each group). After two months, when clear increases in weight gain and calorie intake in the latter group were evident, eight animals from each group were killed for analysis. For one further month, eight animals from each group received low doses (1-3 mg/kg/day) of d-fenfluramine in drinking water, another eight served as untreated controls, and the remaining eight were pair-fed to the treated groups. On killing, the interscapular brown adipose tissue (BAT) mass, and also BAT mitochondrial protein and uncoupling protein contents, and BAT mitochondrial cytochrome oxidase activity and GDP-binding were measured. Gross brain chemical changes were assessed by measuring whole brain contents of serotonin, noradrenaline and dopamine. The palatable diet produced clear increases in weight gain, calorie intake, total BAT mass, BAT mass with respect to body mass, total BAT mitochondrial protein and total amounts of uncoupling protein in each case; however, BAT mitochondrial protein per unit of BAT mass was not significantly increased, nor was the amount of uncoupling protein per mg of mitochondrial protein. Small, but variable, increases in brain neurotransmitter contents were observed. Drug-treated animals showed marked reductions in calorie intake and body weight compared to untreated controls but no significant decreases in body weight compared to pair-fed controls were evident. The pair-fed (i.e. 'slimming') groups displayed a decrease in BAT thermogenic parameters: d-fenfluramine partially prevented these decreases. PMID- 2583918 TI - Use of fluoxetine, a selective serotonin-uptake inhibitor, in the treatment of obesity: a dose-response study (with a commentary by Michael Weintraub). AB - Pharmacologic measures which increase serotonergic activity in the brain decrease food consumption and lead to decreased weight in animals. Fluoxetine, an inhibitor of serotonin reuptake, decreases food intake in animals and is associated with weight loss in depressed and otherwise healthy obese patients. To determine the most effective daily fixed dose which causes weight loss in nondepressed obese patients, fluoxetine (10, 20, 40 or 60 mg) or placebo was administered once daily for 8 weeks to 655 patients consisting primarily of women (mean age 40 years, mean weight 95 kg). Diet and activity were not controlled. The placebo-treated patients lost 0.6 +/- 2.3 kg. With the 60-mg fluoxetine dose, patients lost an average of 4.0 +/- 3.9 kg (P less than 0.001), with intermediate responses at the lower doses. Weight loss was proportional to the initial body mass index (weight/height squared). There were no statistically significant differences between any fluoxetine treatment group and placebo for discontinuations from the study. There were statistically significant dose dependent increases in reports of asthenia, somnolence and sweating. Thus, fluoxetine 60 mg daily appears to be potentially effective for use in weight reduction. PMID- 2583919 TI - Body composition and in vitro lipid metabolism of overfed hypophysectomized rats. AB - Hypophysectomized (hypox) rats were fed ad libitum or were tube-fed increasing levels of their normal food intake. Sham operated (sham) rats were tube-fed to maintain their normal rate of growth or were fed 150 percent of their ad libitum food intake. This was equivalent to the highest intake of hypox rats. Overfeeding continued for 20 days. Overfeeding hypox rats increased body weight almost entirely by hypertrophy and hyperplasia of body fat depots. Overfeeding did not promote growth of lean tissue in hypox rats. Serum insulin increased with higher levels of food intake and extreme overfeeding resulted in hyperinsulinemia and hyperglycemia in hypox rats. Serum thyroid hormones and corticosterone were lower in hypox than sham rats and were not significantly changed by overfeeding. Adipose and hepatic fatty acid synthesis and esterification and adipose glycerol release were measured in vitro. Although serum insulin increased, peripheral tissue of overfed hypox rats remained insulin resistant. Rates of hepatic and adipose lipid synthesis and adipose lipolysis appeared to be determined by nutrient availability rather than being dependent upon pituitary factors. PMID- 2583920 TI - Effects of rapid glucose infusion on in vivo and in vitro free fatty acid re esterification by adipose tissue of fasted obese subjects. AB - Adipose tissue lipolysis and fatty acid re-esterification were examined simultaneously in vivo and in vitro in fasted human subjects receiving a constant intravenous infusion of 14C palmitate and large intravenous infusions of glucose and insulin. Under these circumstances, the plasma [FFA] declines rapidly while the specific activity of plasma FFA increases. Plasma [glycerol] remains stable or declines slowly. These in vivo changes in FFA and glycerol metabolism appear to reflect increased adipose tissue re-esterification of FFA, without an attendant decline in rate of lipolysis. However, in vitro rates of re esterification in gluteal adipose tissue did not change sufficiently to account for the in vivo phenomena. We conclude that: (1) re-esterification in adipose tissue is an important mechanism for the decline in [FFA] induced by glucose infusion in fasted man, but in vitro studies of adipose tissue from a gluteal site do not explain the changes in plasma free fatty acid levels; (2) our data suggest that control of the net mixture of metabolic fuels leaving the adipocyte may be under the influence of pericellular blood flow in addition to ambient humoral factors or intrinsic characteristics of the adipocyte. PMID- 2583921 TI - A positive correlation between energy intake and body mass index in a population of 1312 overweight subjects. AB - The energy intake (EI) of 1312 overweight subjects was assessed using the research dietary history method. EI was positively associated with overweight--as expressed by the body mass index (BMI)--in both males and females. Such findings are at variance with earlier reports of low dietary intakes in the obese and of an inverse relationship between EI and BMI. This discrepancy could be related to the dietary-interviews method used and/or to differences in the degree of motivation of the obese subjects in the various studies. On the other hand, our results are consistent with the positive relationship between energy expenditure (EE) and BMI previously reported in the literature and with the expected EE of our subjects. PMID- 2583922 TI - Short-term weight loss and exercise training effects on glucose-induced thermogenesis in obese adolescent males during hypocaloric feeding. AB - Our purpose was to examine the effect of short-term weight loss and exercise training on the thermic effect of a glucose load in lean and obese adolescents. Nine obese (age 14.3 +/- 0.3 years, mean +/- s.e.m.) boys were examined during the first (Ob-pre) and sixth (Ob-post) week of caloric restriction (1300-1500 kcal/day, 5441-6279 kJ/day) and aerobic exercise conditioning (walk/jog/swim/calisthenics), and compared to age-matched lean controls (Con). A 100-g oral glucose tolerance test (OGTT) was administered while simultaneously measuring energy expenditure by indirect calorimetry every 30 min for 3 h. Posttest results revealed a decrease in body weight and body fatness in obese boys, but not to the level of that in lean controls (P less than 0.01). The thermic effect of glucose, calculated as the area under the response curve for three hours in excess of resting metabolic rate, was similar in Ob-pre and Con (0.77 +/- 0.14 vs. 0.57 +/- 0.28 kcal/kg lbm/3h), but decreased in Ob-post (0.29 +/- 0.08 kcal/kg lbm/3h, P less than 0.01). The area under the response curve for glucose was elevated in Ob-pre (328.1 +/- 12.2 mg/dl/3h) compared to Con (270.4 +/- 21.4 mg/dl/3h). The insulin response was similar in Ob-pre and Con (120.4 +/- 11.3 vs 125.6 +/- 12.4 mU/ml/3h), but decreased in Ob-post (89.6 +/- 15.1 mU/ml/3h, P less than 0.05). Thus, the improvement in peripheral insulin sensitivity with short-term exercise and weight loss was unaccompanied by favorable alterations in carbohydrate-induced thermogenesis in obese adolescents. PMID- 2583923 TI - Preliminary assessment of very low calorie diets by conventional and signal averaged electrocardiography. AB - Fatalities accompanying the use of very low calorie diets have been attributed to cardiac arrhythmias, which may have been associated with myocardial catabolism and hypokalemia. Delayed activation of damaged regions of myocardium may result in low amplitude potentials late in the QRS complex which have been associated with sustained ventricular tachycardia. We used the techniques of routine electrocardiography, signal averaging of the surface electrocardiogram and ambulatory electrocardiographic (Holter) monitoring to evaluate a group of 11 obese men (116 +/- 14 kg) who consumed a potassium-supplemented 660 kcal/day (2763 kJ/day) milk-based liquid diet for 95 +/- 14 days. Electrocardiographic measurements were made before beginning the diet, during the final week on the diet, and after refeeding. Corrected QT interval, QRS voltage and duration, absence of signal-averaged late potentials and ventricular ectopy during 24 h Holter monitoring during the diet and refeeding did not differ from baseline determinations at any point in the obese subjects. In this study, which involved only 11 subjects, neither standard electrocardiographic techniques nor a newer signal-averaging technique revealed any electrocardiographic changes from the diet. A very large population would have to be studied to evaluate the usefulness of these techniques in predicting myocardial damage serious enough to cause arrhythmias. Until such studies are available, the safety of such diets remains unknown. PMID- 2583924 TI - Effect of massive obesity on low and high density lipoprotein binding to human adipocyte plasma membranes. AB - Adipose tissue is a major cholesterol storage organ in man, and turnover of this slowly exchangeable pool is dependent on low and high density lipoproteins which deliver and remove cholesterol from this site. To determine whether lipoprotein binding is altered in the obese state, we examined the binding of low density lipoprotein (LDL) and high density lipoprotein (HDL2 and HDL3) to purified adipocyte plasma membranes obtained from omental fat depots of massively obese patients (BMI greater than 40 kg/m2) and lean subjects. The specific binding and uptake of 125I-HDL2 and 125I-HDL3 were greater for obese than for lean adipocytes. Scatchard analysis of binding studies using purified adipocyte plasma membranes and varying amounts of labeled HDL2 or HDL3 demonstrated a higher binding affinity (lower Kd) for HDL2 and higher binding capacity (Bmax) value for both HDL2 and HDL3 in obese as compared to lean. 125I-LDL specific binding was somewhat lower in obese than in lean membranes but this difference was not statistically significant. The cholesterol content of isolated omental adipocytes expressed on a cellular basis or as the cholesterol/triglyceride ratio (mg chol/g of lipid) were similar in the obese and lean subjects. Furthermore, 125I-LDL, 125I-HDL2 or 125I-HDL3 specific binding did not correlate with cellular cholesterol content or with cholesterol/triglyceride ratio. These findings indicate that lipoprotein binding to adipocytes is altered in obesity and is characterized by up-regulation of HDL (particularly HDL2) binding with little change in LDL binding. We conclude from this study that obesity has a profound effect on the expression of HDL binding sites in human adipocytes and that LDL and HDL binding in fat cells are regulated differently. PMID- 2583925 TI - Reversal of dietary obesity is influenced by its duration and severity. AB - A model of dietary obesity was developed, in adult male rats, where duration of feeding of a high fat diet (HFD; 60 percent of calories as fat) influenced capacity to reverse the obese state following a reduction in dietary fat. After 17, and again after 30 weeks, groups of HFD fed rats were returned to ad libitum feeding of a low fat, chow diet (C; 14 percent fat). The rats switched from HFD to C after 17 weeks returned to control levels of body weight and body composition, but the rats switched from HFD to C after 30 weeks did not. This latter group remained heavier than controls without ingesting more energy, indicating an increased energy efficiency and a reduction in energy requirements. These results suggest that energy balance during development of dietary obesity may be different from energy balance in long-standing dietary obesity. In addition to demonstrating that duration (and/or severity) of dietary obesity is an important variable in the potential reversal of the obese state, the results provide further evidence that persistent obesity is not maintained solely by an elevated energy intake. A corollary to these findings is that treatment of dietary obesity may be more effective if begun early. PMID- 2583926 TI - The association of lifetime weight and weight control patterns with diabetes among men and women in an adult community. AB - We examined the association of degree and duration overweight, dietary habits and exercise with non-insulin dependent diabetes mellitus risk in a defined population of 886 men and 1114 women who were aged 50 years and older when examined in 1984-1987. After an oral glucose tolerance test, 142 men and 142 women were classified as diabetic using WHO criteria. Compared to those with appropriate childhood weight, reported underweight as a child significantly increased the rate of diabetes as an adult (RR = 1.3, P less than 0.05). Underweight as a teenager was also associated with an increased rate (RR = 1.3, P less than 0.05). Underweight as a teenager was also associated with an increased rate (RR = 1.4, P less than 0.01). In adults with current body mass indices (weight/height2) greater than 26, the diabetes rate was significantly higher for those underweight as children (RR = 1.7, P less than 0.01). A multivariate logistic regression analysis of adult diet and weight behaviors, adjusting for age and current smoking, found that a weight gain or fluctuation between the ages of 40 and 60 of 10 lbs or more significantly increased the diabetes rate (RR = 1.4, P less than 0.05; RR = 1.7, P less than 0.01). Weight gain between age 18 and the 1984-1987 visit also significantly increased the rate (RR = 1.4 per 17.3 percent, P less than 0.001). Exercise as the only means to control weight was associated with a significantly reduced diabetes rate (RR = 0.05, P less than 0.05). PMID- 2583927 TI - Melatonin potentiates the effects of naloxone on reserpine-induced catalepsy in the rat. PMID- 2583928 TI - The relationship of serotonin metabolism and melatonin secretion to the pathophysiology of tardive dyskinesia. PMID- 2583929 TI - Neurotrophic effect of angiotensin II, vasopressin and oxytocin on the ventral spinal cord of rat embryo. AB - We studied trophic effects of angiotensin II, vasopressin and oxytocin on explanted ventral spinal cord cultures from 13-14-old day rat embryos. There was a significant neurite promoting effect in angiotensin II and vasopressin-treated cultures. Angiotensin II had the most potent effect at any concentrations. It became clear that minimum effective concentration was 10(-8) M in angiotensin II and vasopressin respectively. Effect of these two neuropeptides was concentration dependent. However, oxytocin had no neurotrophic effect at any concentrations. Our results demonstrated that angiotensin II and vasopressin have a neurotrophic effect on ventral spinal cord in cultures, and may contribute to therapeutic strategy of amyotrophic lateral sclerosis. PMID- 2583930 TI - The influence of piracetam on digoxin up-take by different rabbit tissues in vitro. AB - The action of increasing piracetam concentration on the digoxin up-take by various rabbit tissues was investigated in vitro. 125J-digoxin was used and radioactivity was counted in a gamma scintillation counter. Piracetam 100 micrograms/ml has a small increasing action on digoxin up-take by parenchymatous rabbit tissues. This action may be due to the beneficial effect of the substance on tissue microcirculation and cell metabolism. This action is equilibrated or reversed by piracetam 200 micrograms/ml and 400 micrograms/ml. It is suggested that piracetam displays digoxin from its binding-sites but these concentrations are above those ones used for clinical purposes. PMID- 2583932 TI - The early prediction of school learning problems. AB - The purpose of this research was to determine a reliable and realistic set of variables for teachers to assist in early identification of children with special needs. Sixty-four kindergarten children participated in the study, 32 identified as high achieving and 32 identified as low achieving by their teachers. Variables included were information from questionnaires answered by parents and teachers and results of standardized tests. Based on the results of the analyses, variables and tests are suggested for distinguishing between groups of children who may experience school success or difficulties. PMID- 2583931 TI - Involvement of arcuate nucleus of hypothalamus in the descending pathway from nucleus accumbens to periaqueductal grey subserving an antinociceptive effect. AB - The present study was performed to explore the possible involvement of the arcuate nucleus of hypothalamus (ARH) and beta-endorphinergic pathway in the connection from nucleus accumbens to periaqueductal grey (PAG). It was found that the analgesic effect of morphine administered to nucleus accumbens of the rabbit was significantly attenuated by the antiserum against beta-endorphin (beta-EP) injected into PAG. The antagonistic effect was totally abolished by lesioning of the ARH. However, in the rabbit with ARH lesioning, no significant change in basal nociceptive threshold was seen nor was there any significant change in the efficacy of analgesia induced by injecting morphine into nucleus accumbens. The latter effect was attenuated by intra-PAG-administered naloxone, as in the normal control rabbits. These results indicate that (1) ARH and its efferent beta endorphinergic fibers are involved in the descending pathway from the nucleus accumbens to PAG, subserving an antinociceptive effect, (2) endogenous opioid peptides other than beta-EP seem to play an equally important role in mediating analgesia. PMID- 2583933 TI - Orchestration of multiple codes in developing readers: an alternative model of lexical access. AB - An alternative model of lexical access, based on recent PET scan studies showing localized coding operations in multiple brain sites, is proposed. Lexical access is viewed as a process of orchestrating multiple connections between corresponding visible language and oral language coding operations instead of a place--the internal lexicon--to which stimulus words gain access directly or indirectly. In both Study 1 (end of 1st grade) and Study 2 (mid 2nd and mid 4th grade) speed of naming phonically regular words, in which every letter can be phonemically coded, and of naming phonically irregular words, in which every letter cannot be phonemically coded, was not significantly different, indicating that naming can be based on a phonetic code connection rather than phonemic code connections. In both Study 1 and Study 2 speed of correctly accepting phonically regular real words was significantly faster than speed of correctly rejecting nonsense words on lexical decision, showing that absence of a semantic code is not detected as quickly as presence of a semantic code is. In both Study 1 and Study 2 speed of naming a phonically regular real word was significantly faster than speed of naming a nonsense word, demonstrating that naming is facilitated when two connections--between a printed word and its phonetic code and between a printed word and its semantic code--are activated. These findings held whether a key press (Study 1) or voice key (Study 2) response was used. Taken together, the results suggest that the whole word-phonetic code connection may be completed before the whole word-semantic code connection, both of which may precede the letter-phoneme connection in time. PMID- 2583934 TI - Psychological stress and oxytocin treatment during pregnancy affect central norepinephrine, dopamine and serotonin in lactating rats. AB - The aim of these experiments was to investigate the effects of psychological stress and oxytocin treatment on levels of norepinephrine, dopamine and serotonin in the hypothalamus, hippocampus, striatum, midbrain and brainstem of lactating females. Stress and oxytocin treatment were applied during the third trimester of pregnancy, and females examined on day 6 and day 21 postpartum. The results indicated that serotonin levels were significantly increased on day 6 following unpredictable novelty stress during pregnancy. Furthermore, a marked reduction in serotonin levels in the hypothalamus, hippocampus, midbrain and brainstem was observed as a result of oxytocin treatment on both Day 6 and Day 21 postpartum. These results are in stark contrast to those obtained for nulliparous females in a previous study and suggest an important distinction between nulliparous and lactating females with respect to the effects of psychological stress and oxytocin treatment on central monoamine levels. PMID- 2583935 TI - The neuropsychology of de novo patients with idiopathic Parkinson's disease: the effects of age of onset. AB - One hundred de novo patients with Parkinson's disease (PD) were classified into two groups according to age of onset of symptoms. Seventy two patients were under 70 years and 28 were 70 years and over. All patients were given neurological and neuropsychological assessments, and the severity of the signs was rated on a modified Columbia scale. The neuropsychological assessment was also administered to 50 age-and-education-matched controls. The neuropsychological test battery included tests of verbal learning, visual memory, verbal fluency, visuospatial skill, simple and choice reaction time, language and maze learning. The late onset patients had significant impairment in nonverbal reasoning, auditory verbal learning, visual memory and choice reaction time in contrast to early-onset patients and controls. A relationship was found between bradykinesia and widespread cognitive impairment. Severity of tremor was found to be significantly correlated with impairment in auditory verbal learning, visual memory and increased choice reaction time, while rigidity was found to be associated with cognitive impairment in verbal fluency and visuospatial skill. Using DSM II criteria, 39% of the late-onset and 8% of the early-onset group were classified as demented. Dementia was more common in patients with bilateral symmetrical disease and in those patients with marked tremor and bradykinesia. The pattern of cognitive impairment in PD was consistent with that associated with a subcortical dementia. This study confirms that the expression of PD is markedly influenced by the age of onset. PMID- 2583936 TI - Cognitive function in multiple sclerosis and its relation to functional abilities. AB - The performance of patients with multiple sclerosis (MS) on selected neuropsychologic tests was examined to ascertain the applicability of such examinations to diagnosis. Twenty-four patients with definite or probable MS, and sixteen age- and education-matched control subjects were given a battery of tests to assess intellectual functions. The results indicate that the MS patients had cognitive impairment. Severity of disability was not significantly correlated with cognitive impairment. Impaired cognitive functioning, which is often not detected through routine examination, may occur in the disease. These deficits may represent manifestations of otherwise undetectable plaques in the subcortical white matter. PMID- 2583937 TI - Hemisphericity and student achievement. AB - Hemispheric preference, the newest element of learning style, refers to the tendency of a person to use one side of the brain to perceive and function more than the other. The objective of the study was to investigate the psychological domain of learning styles in terms of the hemispheric patterns of Singapore Secondary Two students in the three achievement levels, namely Normal (low achievers), Express (average achievers), and Special (high achievers). Using the Cognitive Laterality Battery (Gordon, 1986) to measure the students' hemispheric dominance, the study found that it is in the psychological domain of the students' learning styles, in terms of their hemispheric dominance that the Secondary Two students in the three achievement levels are distinctly different. PMID- 2583938 TI - Effects of an overnight fluid infusion on cognitive functions in preoperative patients. AB - The results of the present study show that subjects who received an overnight infusion of isotonic fluid did significantly less well at particular neuropsychological tests than controls who did not receive such an infusion. The relevant test parameters involved aspects of word list learning, and concept shifting on a complex speed task. Potentially biasing factors such as anxiety, disturbed sleep, education and age could be discarded. With respect to the physiological mechanism involved, the results suggest that a relatively expanded extracellular volume without dilutional hyponatremia might underlie the diminished performance. The experimental group did not lose weight overnight, and the hemoglobin and haematocrit level of the experimental group were significantly different from those of the control group; the blood pressure, plasma electrolytes and osmolality were not different. The present results provide evidence that disturbances in fluid homeostasis may affect cognitive performance. PMID- 2583939 TI - Lateral preference and processing style. AB - Lateral preference, as measured by the Lateral Preference Schedule, was related to the Simultaneous, Sequential and Achievement Scales of the Kaufman Assessment Battery for Children (K-ABC) for a sample of 44 normal elementary school children. The results showed that, as eye preference and general laterality became more mixed, children tended to score lower on all three scales of the K ABC. This relationship was strongest for tasks related to classroom achievement. PMID- 2583940 TI - Psychomotor decline can be described by discontinuities in response trajectories: comments on Vrtunski and Patterson (1985). AB - Five methodological and experimental design concerns are identified in Vrtunski and Patterson's (1985) article. The discussed concerns involved: (a) the use of misleading premotor segment terminology, (b) the uncertain status of the repeated measures sphericity assumptions, (c) mean calculations across unequal trials of the four levels of stimulus conditions, (d) improper selection of a main effect for post hoc analysis and discussion of these results when a significant interaction was present, and (e) conflicting text and table values. These concerns have prompted us to question their psychomotor decline conclusions. And unless Vrtunski and Patterson can convince us that these concerns are unjustified, we have no choice but to doubt seriously the validity of their conclusions. PMID- 2583941 TI - The Hoffmann reflex from the flexor pollicis longus of the thumb in left-handed subjects: spinal motor asymmetry and supraspinal facilitation to Cattell's intelligence test. AB - The spinal motor asymmetry was studied in left-handers. Hand preference was assessed by Geschwind scores (GS), and hand skill by peg moving task, the reflex responses were recorded from the long flexor muscle of the thumb. The H-reflex could be elicited by averaging during cortico-spinal facilitation (voluntary isometric force). The Cattell's Culture Fair Intelligence Test was used to assess the individual differences in mental abilities. H-reflexes were found to be significantly larger on the left than the right side. The amplitude of H-reflex increased linearly with force applied to transducer by the thumb. This facilitation was more pronounced for the left than the right reflexes. Removal of the visual visual input caused facilitation in H-reflex (supraspinal disinhibition). Post-activation potentiation was also observed in H-reflex. There was a positive linear correlation between the degree of left-hand preference ( GSs) and left-hand skill. The correlation for the right-hand skill was not significant. There was a linear correlation between the degree of left-hand preference and the right minus left hand skill. There was an inverse correlation between left-hand skill and H-reflex from left. The correlation for the right side did not reach the 5% significance level. The force-reflex relation did not show any significant change to IQ for the right H-reflex. The left H-reflexes were significantly larger in subjects with high IQ than those with low IQ. The regression line and its slope for the force-reflex relation on the left was found to be higher in subjects with high IQ than those with low IQs. There was a positive linear relationship between IQ and H reflex from left. The correlation for the right side was not as pronounced as that for the left side. The left minus right H reflex was also positive linearly correlated with IQ. These results provide further evidence for the psycho-motor hypothesis (Tan. 1988b) as well as the spinal motor asymmetry to handedness. It was suggested that lateralization of cognitive and motor functions would be essential to create subjects with high psychomotor capacity. PMID- 2583942 TI - The H-reflex recovery curve from the wrist flexors: lateralization of motoneuronal excitability in relation to handedness in normal subjects. AB - Spinal motor asymmetry was studied in relation to handedness. Hand preference was assessed by Oldfield's Questionnaire and Geschwind scores. hand skill was evaluated by a peg moving task. The motoneuronal excitability was assessed by the size and recovery curve of the H-reflex elicited by stimulation of the right and left median nerves. H-reflex was recorded by cup electrodes placed over the wrist flexors. The mean reflex latencies from the right and left sides were 23.4 and 23.2 ms, respectively. The mean amplitude of the maximum H reflex was significantly higher on the right side than the left side in right-handers without familial sinistrality (FS). There were no significant side differences in the amplitudes of H-reflexes of the right-handers with FS. A genetic factor was suggested to involve this left shift of spinal motor lateralization in right handers with FS. The recovery curve studies showed that the motoneuronal excitability was higher on the right than the left in right-handers without FS. There was no excitability difference between the right and left sides of the right-handers with FS. In left-handers, the motoneuronal excitability was significantly higher on the left than the right side. Voluntary flexions of the wrist increased the H-reflex especially on the right side of the right-handers. There was no relationship between this corticospinal facilitation and baseline EMG activity. The H-reflex amplitude was found to be inversely correlated with hand skill in right-handers. It was concluded that motoneuronal excitability is associated with handedness and also depends on FS. It was suggested that small reflexes are especially suitable in fine motor control of rapid aimed-movements, as the well-established relation between the size of motor units and fine motor control. PMID- 2583944 TI - Neurotrophic action of autopsied ventral spinal cord extracts in patients with amyotrophic lateral sclerosis on the ventral spinal cord of rat embryo. AB - The effects of ventral spinal cord extracts from normal controls and patients with amyotrophic lateral sclerosis (ALS) on neurite appearance in ventral spinal cord explant of 13-day-old Sprague-Dawley rats were investigated. Ventral spinal cord extracts from normal controls and ALS were significantly more effective in stimulating growth than control medium only. There was no statistically significant difference between normal and ALS ventral spinal cord extracts in growth of neurites. Our results may be an important for the consideration of the hypothesis that ALS may be a disorder of motor neuron growth factors. PMID- 2583943 TI - Trophic effects of cholecystokinin and calcitonin gene-related peptide on ventral spinal cord in culture. AB - We studied trophic effects of cholecystokinin (CCK) and calcitonin gene-related peptide (CGRP) on explanted cultures of ventral spinal cord from 13-14 old day rat embryo. There was a significant neurite promoting effect (NPE) in CCK-treated culture. The neuritic extension of ventral spinal cord exceeds control values 3.5 6.5 times. Otherwise, CGRP and NPE at any concentration. The possible mechanism of trophic effect of CCK on ventral spinal cord was briefly discussed. Our results may contribute to a therapeutic strategy for amyotrophic lateral sclerosis. PMID- 2583945 TI - Attenuation of reserpine-induced catalepsy by melatonin and the role of the opioid system. AB - Several reports have indicated that melatonin influences motor activity in animals and humans. Melatonin has been reported to attenuate the rigidity and tremor of Parkinson's disease. Some of the behavioral effects (e.g., analgesic and anticonvulsant properties) of melatonin have been reported to be mediated through interactions with the endogenous opioid peptides. We investigated the effect of melatonin on reserpine-induced catalepsy in the rat and, additionally, examined whether this effect is modified by opioid peptides. Melatonin was found to attenuate markedly the duration of reserpine-induced catalepsy. These effects were potentiated by administration of the opiate agonist nalbuphine hydrochloride, while naloxone partially reversed the catalepsy reducing effect of melatonin. These findings suggest that the motor effects of melatonin may involve critical interactions with opioid peptides, and support the postulated reciprocal interactions between melatonin and opioid peptides that previously have been demonstrated for the analgesic and anticonvulsant properties of melatonin. PMID- 2583946 TI - Spinal motor lateralization assessed by recovery curve of H reflex from wrist flexors in right-, and left-handed normal subjects. PMID- 2583947 TI - Lateralization of the Hoffmann reflex from the long flexor thumb muscle in right- and left-handed normal subjects. PMID- 2583948 TI - Naloxone analgesia: an update. PMID- 2583949 TI - Brainstem auditory evoked potentials in patients with multi-infarct dementia and dementia of the Alzheimer type. AB - Brainstem auditory evoked potentials (BAEPs) were recorded in 25 patients with multi-infarct dementia (MID) (mean age 71.2 years), 16 patients with dementia of the Alzheimer type (DAT) (mean age 70.6 years), and 34 normal subjects (mean age 69.1 years). Both MID and DAT patients showed significant prolonged interpeak latencies between waves I and V (I-V IPLs) compared to normal subjects (p less than .001 and p less than .01, respectively). In patients with MID, both I-III IPLs and III-V IPLs were significantly longer than those of normal subjects (p less than .01 and p less than .01 respectively). On the other hand, only III-V IPLs were significantly prolonged in patients with DAT (p less than .01). There were no significant differences between MID and DAT with regard to any of the IPLs. Present results suggest that the brainstem lesions are located in the auditory pathways in patients with MID and DAT. However, with BAEP measurements, we were not able to discriminate between patients with MID and DAT. PMID- 2583950 TI - Wakefulness-sleep modulation of the surface and depth auditory evoked potentials in man. AB - Amplitude and latency changes of early and late components of surface and depth auditory evoked potentials were determined during wakefulness-sleep steady state shifts in epileptic patients, with implanted electrodes used as an electrophysiological procedure for surgical treatment of temporal lobe seizures. Early surface (I and V) and depth (N8 and N15) components of the auditory brainstem potentials and late surface (P2 and N2) and depth (B and C) components of the auditory evoked potentials were produced by either 8/s or single clicks, delivered monoaurally and simultaneously recorded from the vertex and contralateral thalamic (lateral geniculate thalamic nucleus) and frontotemporal (amygdala, hippocampus and orbitofrontal cortex) regions, while patients spontaneously shifted from initial wakefulness (W1) to slow wave sleep (SWS I, II and IV), to paradoxical sleep (PS) and to final wakefulness (W2). Amplitude of late surface (P2 and N2) and depth (B and C) components significantly decreased when patients shifted from SWS IV to PS and increased from PS to W2. Latency of components P2 and B increased while that of components N2 and C decreased from SWS IV to PS. No latency changes in late components were found from PS to W2. In addition, amplitude and latency of P2 and B components significantly decreased while those of N2 and C increased from W1 to SWS IV. Polarity of all late components remained unchangeable during all wakefulness-sleep state shifts, with the exception of that of component C which reversed from W1 to SWS IV. In contrast, early surface (I and V) and depth (N8 and 15) components showed no systematic changes in amplitude and latency during all consecutive wakefulness sleep shifts, with the exception of a significant increase amplitude but no latency of component V from PS to W1. PMID- 2583951 TI - Long latency cutaneous reflex effect on H-reflex recovery in hemiplegics and paraplegics: a longitudinal study for the assessment of motor function. AB - H-reflex recovery by twin pulses was recorded serially in 10 paraplegics for 5 months and in 23 hemiplegics for 2 months after the lesion. Fifty-one normal subjects acted as controls. The effect of cutaneous tactile stimulation was also studied simultaneously by applying electrical stimuli synchronized with twin pulses to the skin over the lateral border of small toe. In paraplegics, the H reflex recovery curves recorded serially showed a highly depressed pattern during the first two weeks, an almost normal pattern during the second and third months and a significantly elevated pattern during the fourth and fifth months. Whereas cutaneous stimulation in control subjects produced a highly significant late inhibition of H-reflex recovery between 600 ms and 600 ms, in paraplegics it failed to produce any significant effect, except in two, who besides having a normal H-reflex recovery curve even during the first week, showed a substantial amount of cutaneous inhibition of H-reflex recovery, 4 months after the lesion. A highly depressed pattern of H-reflex recovery was observed on the affected side of the majority of hemiplegics during the first week after the lesion, many of them showing similar pattern on the "unaffected side" also. The serial study showed very good improvement in all hemiplegics both in terms of H-reflex recovery pattern and the amount of cutaneous inhibition. The observations in present study suggest preservation and/or restoration of supraspinal influences in many hemiplegics and in at least two paraplegics. The study also shows that a serial recording of H-reflex recovery curve and the amount of cutaneous reflex effect on it, is a very sensitive method of assessing the supraspinal influences on the spinal motoneurones and so can be of immense help in the diagnosis and prognosis in hemiplegics and paraplegics. PMID- 2583952 TI - Left-sided lateralization of immune disorders in a left-handed female subject. PMID- 2583954 TI - Medical management of the glaucoma patient: an interdisciplinary perspective. Proceedings of an international symposium. Paris, France, September 16-18, 1988. Abstracts. PMID- 2583953 TI - Autoimmune mechanisms in Parkinson's disease. PMID- 2583955 TI - Reliability and factor structure of the Portuguese version of Self-Reporting Questionnaire. AB - The Self-Reporting Questionnaire is a screening instrument devised by the WHO to identify minor psychiatric morbidity in primary care settings and the community in developing countries. It has already been widely used although its psychometric properties are not yet completely explained. The present article describes the following properties of the Portuguese version of the SRQ-20: a) coefficients of internal consistency; b) inter-rater reliability coefficients, and c) a factor analysis. Internal consistency, measured by the KD20 method, was 0.81. The intra-class correlation coefficient obtained from simultaneous scoring of four interviewers was 0.96, considerably high, as expected from a structured instrument. In the factor analysis four main factors accounted for 41% of the total item variance, and they could be reasonably identified as Decreased Energy, Somatic symptoms, Depressive mood and Depressive thoughts. PMID- 2583956 TI - Social class, psychological wellbeing and minority status in Northern Ireland. AB - The present study sought to evaluate the completing claims of the social stress hypothesis and the social selection hypothesis which both claim to explain the relationship between social class and psychopathology. Scores on a self-report measure of psychological wellbeing, the General Health Questionnaire (GHQ) were obtained from a random sample of 581 respondents in Northern Ireland. An analysis of variance comparing majority (Protestant) and minority (Catholic) group males and females at three socioeconomic levels produced a Religion X Social Status interaction. This was due to a trend of increasing symptoms with decreasing social status among Protestants and the reverse phenomenon among Catholics. It was concluded that the results while similar to those reported earlier by Cochrane and Stopes-Roe, provided no clear support for either the social selection hypothesis or the social stress hypothesis but were possibly related to local factors connected with emigration or the ongoing political violence in Northern Ireland. PMID- 2583957 TI - Sex differences in schizophrenia. AB - Demographic and clinical characteristics of 275 schizophrenics consecutively admitted to seven hospitals were examined. Males were younger than females when first hospitalized, diagnosed and treated. Psychiatrists rated on two rating scales by using a structured interview to compare the symptomatology. Female schizophrenics were more agitated, inappropriate, silly, irrelevant, over talkative, and exhibiting more flight of ideas, while male schizophrenics were more slowed, hypoactive, grandiose, withdrawn, and showing more blocking, auditory hallucinations and poor communications. Katz Adjustment Scales were rated by the patients and their relatives. Female schizophrenics were perceived by relatives to be more helpless and withdrawn-depressed than male schizophrenics. PMID- 2583959 TI - Parental communication and psychological distress in children of Holocaust survivors: a comparison between the U.S. and Israel. AB - To determine how the children of Holocaust survivors in Israel and the U.S. differ on measures of parental communication and psychological distress, we performed a comparative study on 140 subjects in the U.S. and 54 in Israel using a written questionnaire. Respondents in Israel reported more communication by their parents, but also a higher level of demoralization; this may be due to more demoralization among the general population. In both populations, parents' general communication correlated negatively with anxiety, depression and demoralization and positively with guilt. Parents' Holocaust communication resulted in similar findings; however, in Israel only a negative correlation with demoralization reached significance. Parental communication about the Holocaust thus seems to be of less importance in Israel in determining the children's psychological outcome. This may be due to a greater role by Israeli society in forming children's perception of the Holocaust. PMID- 2583958 TI - Psychiatric day care: the users' perspective. AB - The literature on consumer opinion about psychiatric day care is reviewed and a study of the views of day care attenders living in an inner city catchment area who are in prolonged contact with psychiatric services is presented. Attenders were broadly satisfied with their care. Analysis of their verbatim comments suggested that attenders perceived the value of attendance at a day unit in social rather than therapeutic terms. The implications of this finding are discussed. PMID- 2583960 TI - Consultation liaison psychiatry in a Kuwaiti general hospital. AB - The authors analysed the psychiatric profile of 208 general hospital patients referred for psychiatric consultation, about half of these patients presented with parasuicidal behaviour. The diagnoses of depression and adjustment disorders predominated. Characteristics of the referred patients, source of referral and main forms of psychiatric intervention are documented. Means to promote good relationships between psychiatrists and physicians are suggested. The need for a better liaison psychiatric service is emphasised. PMID- 2583961 TI - Characteristics of a rural area community mental health programme County Caroni. AB - The paper describes characteristics and trends in a rural area Community Mental Health programme. Research done by the mental health team supports some of the previously held notions on alcoholism and dispels some myths about parasuicide and suicide. Education at all levels continues to be an important preventative measure in the fight against drug abuse. The effort to set up an Alcohol and Referral Center is partly thwarted by poor community resources. The mental health team has had to enlist the support of service organizations in their educational programmes. More work needs to be done in the area of psychogeriatrics, rehabilitation and family life. The need for closer links between governmental agencies and the community is emphasized. PMID- 2583962 TI - [Determination of the aluminum concentration in body fluids]. PMID- 2583963 TI - [Iodine supply, iodine deficiency and struma prevention]. PMID- 2583964 TI - Diagnosing breast cancer. PMID- 2583966 TI - The best kind of support. PMID- 2583965 TI - Breast cancer: one woman's perspective. PMID- 2583967 TI - Breast reconstruction after mastectomy. PMID- 2583968 TI - Breast cancer. PMID- 2583969 TI - Iowa Health Data Commission update. PMID- 2583970 TI - Enzyme activity in organized systems. Abstracts of the meeting of the Lazio Abruzzi-Molise Group of the Italian Biochemical Society. Rome, June 24, 1988. PMID- 2583971 TI - Protective effects of exogenously administered fructose-1,6-diphosphate from ischemia reperfusion damage induced on isolated rat heart. PMID- 2583972 TI - Microspectroscopic studies on single red blood cells. PMID- 2583973 TI - Peroxidative activity in lymphoid cells evaluated by 2'-7'-dichlorofluorescein diacetate. PMID- 2583974 TI - Modulation of protein kinase C in myogenic differentiation. PMID- 2583975 TI - Effect of X-rays on the differentiation of L5 myoblast cell line. PMID- 2583976 TI - Involvement of the membrane fluidity on the human erythrocyte deformability. PMID- 2583977 TI - Interaction of fusicoccin with specific binding sites: a receptor model in higher plants. PMID- 2583978 TI - Naturally occurring inactive forms of aminotransferases. PMID- 2583979 TI - Liposomal encapsulation of Cu, Zn superoxide dismutase: characterization of enzyme-loaded liposomes and their interaction with human cells. PMID- 2583981 TI - Abstracts presented at the meeting of the Liguria-Lombardia- Piemonte Group of the Italian Biochemical Society. June 14, 1988, Pavia. PMID- 2583980 TI - Electrophoresis pattern of the human platelet subpopulation proteins. PMID- 2583982 TI - Marfan syndrome: a collagen disorder? PMID- 2583983 TI - Tissue and serum gangliosides determination in patients with meningiomas. PMID- 2583984 TI - Molecular defects in genetic variants of human serum albumin. PMID- 2583985 TI - Uptake of polyamines by human lymphocytes. PMID- 2583986 TI - Inhibitors of cholesterol biosynthesis as potential hypocholesterolemic drugs. PMID- 2583988 TI - Polyamines. Abstracts of the Italian Biochemical Society. Padova, October 4, 1988. PMID- 2583987 TI - Nuclear magnetic resonance applied to biochemical problems: structure determination of ganglioside lactones. PMID- 2583989 TI - Calorimetric scanning structural studies on bovine serum amine oxidase. PMID- 2583990 TI - Regulation of lymphocyte carbohydrate metabolism by polyamines. PMID- 2583991 TI - Mechanism of polyamine action on the activation process of protein kinase C. PMID- 2583992 TI - Migraine--a risk factor for dissection of cervical arteries. AB - A case control study technique was employed to test for an association between non-traumatic cervical artery dissection and several possible risk factors. A significant positive association was shown with migraine, independent of type and treatment regimen. No such relationship was found with smoking history, hypertension or past oral contraceptive use. There was, however a significant and independent association with current oral contraceptive use. PMID- 2583993 TI - The vascular "cold patch" is not a prognostic index for headache. AB - Our previous research has determined that the vascular "cold patch" is a valid diagnostic "marker" and is a persistent constituent of the thermal geography of the external carotid region. It has been suggested by Dalla Volta and Anzola (1988) that the cold patch may be a prognostic index of vascular headache physiology; that is, as headaches improve through the use of vasoactive prophylactic medication, the cold patch would decrease in size or disappear. The purpose of this study is an attempt to replicate these findings. Forty migraine patients were randomly selected, and a thermographic re-examination of the external carotid region (forehead) was conducted. The post-treatment thermogram was then compared to the initial pre-treatment thermogram. Thirty subjects demonstrated an improved condition (IC) and ten subjects a worsened condition (WC). The IC Group exhibited a 73.2% reduction in headache frequency following a mean treatment period of 6.3 months. The WC Group demonstrated a 48.1% increase in headache occurrence at a mean treatment interval of fifteen months. Results demonstrated little thermographic difference between the two conditions. Within the IC Group, 46.7% of subjects exhibited and increase in cold patch size with an improved condition, 40% of cold patches remained stable, 6.7% of cold patches reduced in size, and zero cold patches disappeared with successful treatment. Within the WC Group, 20% of cold patches decreased in size with a worsened condition, 40% increased in size, and 40% remained stable. Chi square analysis determined there was no significant difference in cold patch changes between patients whose headache condition improved or worsened (p less than .70).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2583994 TI - Investigation of environmental factors in pediatric headache. AB - This study assessed the environmental conditions surrounding headache for a clinical sample of 38 pediatric headache patients. A parent rating questionnaire, the Children's Headache Assessment Scale (CHAS), was developed and pilot tested as a means of identifying particular environmental events or situations impacting on children's headaches. CHAS items are organized into six functional categories (Stress Antecedents, Physical Antecedents, Attention Consequences, Escape Consequences, Coping Responses, and Medication Use) potentially related to headache activity. Parents filled out the CHAS at an intake evaluation for behavioral medicine treatment, and parents of children who completed treatment filled out another CHAS after therapy. Results showed that the frequency of specific CHAS items varied widely both within and between functional categories, suggesting that headache is affected by a variety of situational factors, some of which are common across many children and others of which are pertinent only for a small proportion of children. The results further suggest that the environmental conditions of headache are open to change by behavioral medicine treatment. In the present study, items reflecting social attention to headache, interference of headache with school attendance, and use of relaxation procedures changed after treatment. The potential value of the CHAS for treatment planning is discussed. PMID- 2583996 TI - Cluster headache: localization. PMID- 2583995 TI - Severe headache and vacation. AB - Of a randomized nationwide adult population sample of 2,073 people, 1,590 (76.7%) were interviewed on their vacation expectations and their determinants using a prestructured questionnaire of 200 questions. Migraine or other severe headache occurred in 14.0% of people 15 to 74 years of age (in 19.7% of women and 8.0% of men). Compared with people without headache, headache sufferers were characterized by less interest in paid or unpaid vacation, more passive ways of spending vacation, more fear and anxiety for their health and human relations, uncertainty of the world situation, fear of global catastrophes and disturbances of work routine and increased family discord during vacation. Headache sufferers were apparently hard-working and conscientious people with a stressed, depressive and resigned character and unable to feel care-free and to relax on vacation. PMID- 2583997 TI - Atypical facial pain, ectasia of the basilar artery, and baclofen: a case report. AB - Atypical facial pain is a clinical syndrome of facial pain that has been related to depression but whose pathogenesis is not known. We describe a 72-year-old woman with a chronic facial pain, and ectasia and left sided deviation of the basilar artery, that responded dramatically to baclofen. This case suggests that vascular compression of the trigeminal nerve may be one of the mechanisms producing this syndrome and in these cases it might respond to baclofen. PMID- 2583998 TI - The relationship of electromyographic and vasomotor activity to MMPI subgroups in chronic headache patients: the use of the original and contemporary MMPI norms. AB - The relationship of electromyographic (EMG) and temporal artery vasomotor activity to MMPI subgroups was examined in 60 chronic headache sufferers. Analysis of the right frontalis data revealed a significant interaction between MMPI subgroup and position (reclining, sitting, standing) with a trend toward the same interaction with the left frontalis. However, this effect was only found when the contemporary MMPI norms were utilized in the formation of the subgroups. No effects were found for the bilateral trapezius EMG or bilateral temporal artery sites. Analysis of the self report data revealed a significant main effect for the Total Pain Score of the Pain Mannequin but not for a current headache intensity rating. Again, the former effect was seen most clearly when the contemporary MMPI norms were used. In general, these data support a Psychological Distress Hypothesis in that patients with significant elevations (greater than 70) demonstrated greater frontalis EMG activity and higher Pain Mannequin scores. Additionally, the data demonstrate the importance of utilizing the contemporary MMPI norms in the formation of subgroups. PMID- 2583999 TI - Vascular headache from extracranial venous malformation. AB - Headache associated with intracranial venous anomalies is well described but headache associated with extracranial venous malformation previously has not been recognized. A case of extracranial venous malformation producing vascular headache is presented. PMID- 2584000 TI - Low brain magnesium in migraine. AB - Brain magnesium was measured in migraine patients and control subjects using in vivo 31-Phosphorus Nuclear Magnetic Resonance Spectroscopy. pMg and pH were calculated from the chemical shifts between Pi, PCr and ATP signals. Magnesium levels were low during a migraine attack without changes in pH. We hypothesize that low brain magnesium is an important factor in the mechanism of the migraine attack. PMID- 2584001 TI - Prevalence and clinical features of migraine: a community survey in Bangkok, Thailand. AB - The authors probed the extent and clinical features of migraine through a community survey in the Bangkok slum. A total population of 540 individuals of both sexes were randomly selected from available subjects. They were interviewed using questionnaires. The response rate was 100%. The prevalence of migraine in the previous year in 135 men and 405 women was 10.4% and 35.3% respectively. The overall prevalence of migraine in this community was 29.1%. In both sexes, the prevalence declined with increasing age and in women, the effect of age was significant (p less than .005). The clinical features of migraine (age of onset, headache profile, neurological symptoms, severity and frequency of headache, familial history, precipitating factors and medications for headache) were analyzed. We concluded that migraine is not uncommon in a low socioeconomic group in Thailand, and that this type of headache is a burden to patients and may have some economic effect. Thus, strategy in prevention and control of migraine should be critically considered. PMID- 2584002 TI - Cryotherapy for headache. AB - 45 patients with migraine or migraine plus chronic daily headache evaluated the effectiveness of a coldwrap for headache relief. 35.5% judged it not effective, 29% judged it mildly effective, 26.5% found it moderately effective, and 9% judged it completely effective. Previous studies on ice treatment for headache are reviewed. PMID- 2584003 TI - The challenge of head and neck cancer in India. PMID- 2584004 TI - Evaluation and treatment of acute laryngeal fractures. AB - Treatment of laryngeal fractures continues to evolve, and the airway now can be restored without stenosis or aspiration in most cases. However, the best treatment of vocal cord dysfunction from trauma remains uncertain, and the value of computerized tomographic scan (CT) is controversial. In this report, we describe the symptoms, radiologic findings, and treatment of 15 consecutive cases of laryngeal trauma. The value of CT for assessing the cricoarytenoid area is discussed. We also found CT to be reliable for defining the extent of soft tissue trauma and for diagnosing the presence and displacement of any fractures. Endoscopic photographs are compared with CT scan photographs to illustrate the correlation of CT with the degree of trauma. Finally, we present a method of laryngeal fracture repair using autologous thyroid cartilage. PMID- 2584005 TI - Endotracheal intubation as an alternative to tracheostomy after intraoral or oropharyngeal surgery. AB - Patients who undergo oral or oropharyngeal surgery usually require a tracheostomy for postoperative airway maintenance. However, the development in recent years of soft endotracheal tubes now provides the alternative of short-term endotracheal intubation, with minimal sequelae. Our favorable experience with the use of short term intubation in children with epiglottitis prompted us to apply the technique to adults. Over a 2-year period at the University of Chicago Medical Center, we successfully used postoperative endotracheal intubation for 19 adult and pediatric patients who underwent major intraoral procedures, thus avoiding the possible complications, discomfort, and anxiety associated with tracheostomy. The patients were given intravenous steroids and antibiotics concomitantly, so that tissue edema and inflammation were minimized. No complications related to intubation and no postextubation airway compromise were noted in any of the patients. PMID- 2584006 TI - Preclinical chemotherapy on human head and neck cancer xenografts grown in athymic nude mice. AB - This study was undertaken to investigate the potential role of xenografts established from human head and neck squamous cell carcinoma (HNSCC) in the selection of new anticancer agents for phase II clinical trials. Eight HNSCC tumor lines were established in NMRI nude mice. The tumor-bearing animals were then treated with drugs at the maximum tolerated dose level. Treatment with drugs known for their activity in 15%-30% of HNSCC patients [cisplatin (CDDP), bleomycin (BLEO), 5-fluorouracil (5-Fu), cyclophosphamide (CY), and doxorubicin (DOX)] caused strong responses in up to 38% and moderate responses in 50%-67% of the HNSCC tumor lines. Methotrexate (MTX), known to cause remissions in about 40% of HNSCC patients, was only minimally active in this model system. A clinically ineffective drug, amsacrine (m-AMSA), was included as a negative control and showed no or minimal activity in all four HNSCC lines tested. A number of experimental drugs that have promising preclinical activity were also tested. Brequinar sodium (Dup 785) and 10-ethyl, 10-deaza-aminopterin (10-EdAM) showed activity in three of five, and two of the four tested tumor lines respectively. N,N-dimethylformamide (DMF) and 5-aza-2'-deoxycytidine (5-aza-dCyd), agents with the capacity to induce differentiation in in vitro systems, showed moderate activity in 43% and 40%, and strong activity in 14% and 40% of the lines, respectively. Our results indicate that the nude mouse xenograft model may play a role in the screening of new drugs, and in particular, it could be of help in the selection of drugs to be tested in phase II HNSCC clinical trials. PMID- 2584007 TI - Use of xenograft bone with aspirated bone marrow for treatment of cystic defect of the jaws. AB - Xenografts of Kiel bone in combination with autologous aspirated bone marrow were used to graft 20 cystic defects in the jaws. Sixteen cases (80%) were successful. Results were evaluated by clinical and radiographic follow-up of the patient up to 4 years (average 2.3 years) after surgery. Inability to create a water-tight closure followed by immediate secondary infection were considered as the causes for failure rather than rejection by the host. PMID- 2584009 TI - Gigantiform cementoma of the jaws. AB - Fibro-osseous cemental lesions of the jaw remain a controversial area of bone/cementum pathology. This article describes the clinicopathological features of 28 lesions classified as gigantiform cementoma. Black women are affected more frequently than other race and sex groups, with a peak frequency of occurrence in the fourth and fifth decades. The posterior mandible is preferentially affected and unifocal lesions (67.9%) occur more frequently than multifocal lesions (32.1%). Dull pain and a centrifugal size increase are the most prevalent presenting symptoms. Of 28 cases with parental and sibling clinical information, there were no cases which exhibited an autosomal dominant genetic association. The pathogenesis of this lesion in relation to other cemental lesions of the jaws, as well as the clinical management of cemental jaw lesions, is discussed. PMID- 2584008 TI - Tracheogastric puncture for vocal rehabilitation following total pharyngolaryngoesophagectomy. AB - Speech rehabilitation postpharyngolaryngoesophagectomy has not received significant emphasis. We describe our experience with five patients who underwent a delayed tracheogastric puncture (TGP) after pharyngogastric anastomosis. When compared to patients who had undergone tracheoesophageal puncture (TEP) after laryngectomy, speech intelligibility and fluency were adequate for conversational speech, but voice quality was characterized by lower pitch, reduced intensity, slower rate, and a "wet" quality. There were no complications related to the TGP. TGP is a safe and often useful procedure for voice and speech restoration in patients who have undergone total pharyngolaryngoesophagectomy and pharyngogastric anastomosis. PMID- 2584010 TI - The tooth as a foreign body in soft tissue after head and neck trauma. AB - Thorough evaluation of dentition is important in the management of craniofacial trauma. Avulsed or fractured teeth in the pulmonary and gastrointestinal tracts can lead to serious complications that are well described. However, the penetration of avulsed teeth into soft tissues of the head and neck is unusual and may not be recognized. Two cases in which a tooth became a foreign body in these soft tissues are illustrative. One patient had bronchoscopy for possible aspiration of an avulsed maxillary canine; it was later found embedded in the premaxillary tissues. The other patient had a right mandibular molar propelled into the posterior triangle of the left side of the neck. Physicians must be aware of dental injury resulting from facial trauma and account for all teeth as part of their evaluation, keeping an open mind as to where a missing tooth might be located. PMID- 2584011 TI - Gorham's disease affecting the maxillofacial skeleton. AB - Twenty-one cases of Gorham's disease in the maxillofacial region are described in the literature. This case is an additional one. The disease has a slight male predominance. All cases involved either the mandible alone or in association with the maxilla or other bones of the head and neck. The most common symptoms were pain, tooth mobility, mandibular pathological fractures, and facial deformity. The mean duration of symptoms prior to diagnosis was 6.4 years. Treatment included surgery, radiotherapy, and various medications, alone or combined. Four patients died of their disease. The diagnosis of the initial biopsy was incorrect in 45% of these cases. The current case appears to be the only one successfully treated by excision and autogenous bone graft reconstruction. In order to make an accurate diagnosis, the histologic features should be correlated with the clinical features. PMID- 2584012 TI - Dermatofibrosarcoma protuberans with regional lymph node metastasis: a case report. AB - The case of a 21-year-old man with dermatofibrosarcoma protuberans of the scalp that spread to deep cervical lymph nodes is presented. Available literature is reviewed, and the infrequency of metastasis is discussed. Since cases of metastases almost always involve recurrent lesions, the importance of wide and deep resection in the initial operation cannot be overemphasized. PMID- 2584014 TI - Thermoluminescence dosimetry of gamma-rays from the Hiroshima atomic bomb at distances 1.91-2.05 km from the hypocenter. PMID- 2584013 TI - Reduction of salivary flow in amyotrophic lateral sclerosis with Scopoderm TTS. PMID- 2584016 TI - Fallout in the hypocenter area of the Hiroshima atomic bomb. PMID- 2584015 TI - A Compton current radiation dosimeter. PMID- 2584019 TI - Some remarks on secondary protective barrier calculation for radiographic installations: NCRP Report No. 49 revisited. PMID- 2584017 TI - Chernobyl radioactivity in a Turkish tea drinker. PMID- 2584018 TI - Routine calibration of automatic exposure control systems for diagnostic x-ray machines: a 5-y progress report. PMID- 2584021 TI - Supra-linear dose-response in the A-bomb study. PMID- 2584020 TI - Dose-response analyses for the Japanese A-bomb survivors. PMID- 2584022 TI - Is transpiration an important mechanism for release of 222Rn to the atmosphere? PMID- 2584023 TI - The future supply of health physicists. PMID- 2584024 TI - Multi-state surveys of indoor 222Rn. AB - The U.S. Environmental Protection Agency provides assistance to states in conducting surveys of indoor 222Rn. Alabama, Kentucky, Tennessee, Wisconsin, and Wyoming completed statistically designed surveys during the 1986-1987 heating season. In all states, probability-based samples of 5800 houses were tested using charcoal canisters exposed for 48 h. Thus, sample results can be validly extrapolated to the target population of all owner-occupied, ground-level houses having listed telephone numbers. Estimates of population parameters (e.g., median) and their associated confidence intervals are given for each state, for geographic regions within states, and for basement and nonbasement houses. Results confirm that 222Rn concentration varies widely from one state to another and from one geographic region to another within a state; however, the same pattern of differences was not evident in basement or nonbasement houses. Short term 222Rn readings appear to follow a log-normal distribution. PMID- 2584026 TI - Beta skin dose determination using TLDs, Monte-Carlo calculations, and extrapolation chamber. AB - The beta doses produced by 90Sr-Y and 204 Tl beta sources were determined using three methods: Monte-Carlo calculations, measurements with TLDs, and measurements with an extrapolation chamber. Excellent agreement was obtained by all three methods, except a TLD nonlinear response to beta s was observed, which gives doses approximately 20% high for the 90Sr-Y source and 5% low for the 204Tl source. Also, analyses performed with low-energy beta s using these methods can determine errors in shield thickness covering TLD elements. Direct measurement of skin dose is not possible by the TLDs because the minimum shield thickness for the elements is 13 mg cm-2. A thinner shield for the elements must be used or the data must be extrapolated. Presently, thinner shields for TLD elements are not available, and the thick shields can lead to significant errors in skin dose when exposed to low-energy beta s. PMID- 2584025 TI - Expected indoor 222Rn levels in counties with very high and very low lung cancer rates. AB - Counties in the U.S. with high lung cancer rates should have higher average 222Rn levels than counties with low lung cancer rates, assuming the average 222Rn level in a county is not correlated with other factors that cause lung cancer. The magnitude of this effect was calculated, using the absolute risk model, the relative risk model, and an intermediate model, for females who died in 1950 1969. The results were similar for all three models. We concluded that, ignoring migration, the average Rn level in the highest lung cancer counties should be about three times higher than in the lowest lung cancer counties according to the theory. Preliminary data are presented indicating that the situation is quite the opposite: The average Rn level in the highest lung cancer counties was only about one-half that in the lowest lung cancer counties. PMID- 2584027 TI - The postnatal growth of ICRP target organs in reference humans: spleen and liver. AB - Attempts to improve radiation dose estimates to infants and children are hampered because of the lack of mathematical models that describe the age variation in anatomical and physiological parameters. Specifically, for one anatomical parameter, organ size, there are no growth models available to the health physics community. In this paper, an empirical mathematical model is introduced for estimating age-specific masses of two ICRP target organs: the spleen and liver. That model, the Power Logistic Additive (PLA) growth model, is fitted to ICRP 23 organ growth data to determine five growth parameters. This model assumes that organs grow under the influence of two main processes: a primary (power function) and a sexual maturation (logistic function) process, which are additive from birth to adulthood. The results show that the model describes the ICRP growth data quite well. Growth parameters and tables listing the predicted masses and mass velocities as a function of age for each organ are provided for application in the ICRP modeling system. PMID- 2584028 TI - Mass loading of soil particles on plant surfaces. AB - Radionuclide-bearing soil particles on plant surfaces can be ingested and contribute to human dose, but evaluating the potential dose is limited by the relatively few data available on the masses of soil particles present on plant surfaces. This report summarizes mass loading data (i.e., mass of soil per unit of vegetation) for crops in the southeastern United States and compares these data to 1) those from other regions and 2) the mass loadings used in radionuclide transfer models to predict soil contamination of plant surfaces. Mass loadings were estimated using the 238Pu content of crops as an indicator of soil on plant surfaces. Crops were grown in two soils: a sandy clay loam soil and a loamy sand soil. Concentrations of soil on southeastern crops (i.e., mg soil g-1 plant) differed by more than a factor of 100 due to differences in crop growth form and biomass. Mean concentrations ranged from 1.7 mg g-1 for corn to 260 mg g-1 for lettuce. Differences in mass loadings between soils were less than those among crops. Concentrations differed by less than a factor of two between the two soil types. Because of 1) the differences among crops and 2) the limited data available from other systems, it is difficult to draw conclusions regarding regional or climatic variation in mass loadings. There is, however, little evidence to suggest large differences among regions. The mass loadings used to predict soil contamination in current radionuclide transfer models appear to be less than those observed for most crops. PMID- 2584029 TI - Uncertainty in predictions of fallout radionuclides in foods and of subsequent ingestion. AB - Uncertainty in predictions from the PATHWAY food-chain model was estimated using Monte Carlo simulation. Uncertainty estimates, measured by the geometric standard deviation (GSD), were obtained for median values of time-integrated concentrations of 131I, 136Cs, and 137Cs in foods and for the corresponding time integrated intakes resulting from ingestion of all foods. The GSDs associated with a given food for the two short-lived radionuclides, 131I and 136Cs, were not significantly different, but they differed from the GSDs for the longer-lived radionuclide. The GSDs for integrated concentrations of radionuclides in milk varied with the time of year fallout was deposited, but uncertainty for nondairy products was relatively independent of the date of fallout deposition. The estimated GSDs were applied to other radionuclides of interest based on physical half-life and ranged from 1.7 to 2.7 for time-integrated intake across all foods for radionuclides with physical half-lives less than 30 d, from 1.8 to 2.3 for half-lives ranging from 30 to 500 d, and from 1.9 to 2.1 when half-lives were greater than 500 d. PMID- 2584030 TI - Cesium-137 in Montana soils. AB - Fallout 137Cs levels in soil were measured at 11 diverse sites throughout Montana. Concentrations in near-surface samples ranged from 20-200 mBq g-1 (0.51 5.41 pCi g-1). Most of the 137Cs was in the top 10 cm of soil. Deeper occurrences were attributed to disturbances by animals and to interstitial flow of small sediment particles within saturated soils. The areal concentrations ranged from 130-748 mBq cm-2 (3.6-20.2 pCi cm-2) and were highly correlated with annual precipitation. PMID- 2584031 TI - Experimental determination of transfer coefficients of 137Cs and 131I from fodder into milk of cows and sheep after the Chernobyl accident. AB - Following the Chernobyl accident in April 1986, the transfer of 131I and 137Cs from feed to milk was studied under experimental and common agricultural conditions. From measurements in different dairy farms in Southern Bavaria, equilibrium transfer coefficients for cow's milk were calculated to be 0.003 d L 1 (range 0.0015 to 0.005) for 131I and 0.003 d L-1 (range 0.0025 to 0.004) for 137Cs. In feeding experiments with cows and sheep under more controlled conditions, milk transfer coefficients of 0.007 d L-1 (range 0.0055 to 0.0081) for 131I and 0.003 d L-1 (range 0.0023 to 0.0053) for 137Cs were obtained for cows, while for sheep the 137Cs transfer coefficient was higher: 0.06 d L-1. The kinetics of the Cs transfer from fodder to cow's milk can be described by two exponential terms assuming biological half-lives in milk of 1-2 d and 10-20 d. The use of a fast component with 1.5 d and a fraction of 0.8, and a slow component with 15 d, gives a good approximation to the kinetics for all cows in this experiment. PMID- 2584032 TI - Isolation and characterization of hot particles from Chernobyl fallout in southwestern Finland. AB - Three types of activity composition have been found in airborne hot particles that were transported long distances from the Chernobyl accident. Their characterization is based on the analysis of single particles isolated from Pinus Sylvestris needles. The average activity of the particles was 130 Bq at the time of the accident. The most common type of particle contains the radioactive species 141Ce, 144Ce, 95Zr and 95Nb; the second type includes 103Ru and 106Ru along with the previous isotopes; and the third contains 103Ru and 106Ru only. Cesium-134 and -137 were present only in very small amounts. The activity composition of the Chernobyl reactor core fuel was similar to the composition of the first and second type particle; apparently the core fuel was only partially volatilized. The main bulk composition of the particles is shown to be U. The average aerodynamic size of the identified hot particles is 10 microns. The particles are rectangular or pentagonal in shape. PMID- 2584033 TI - Uranium assay in milk and drug samples using solid-state track detectors. PMID- 2584034 TI - Long-term measurements of Rn and short-lived Rn daughter concentrations in natural gas from distribution line. PMID- 2584035 TI - Design and evaluation of a cart for the collection and segregation of low-level radioactive waste. PMID- 2584036 TI - Measurements of whole-body radiocesium at the Harwell Laboratory, 1976-1988. PMID- 2584037 TI - Health insurance and welfare reentry. AB - This study presents a theoretical model of welfare reentry that examines the importance of private health insurance in determining whether working recipients terminated from Aid to Families with Dependent Children (AFDC) as a result of the Omnibus Budget Reconciliation Act returned to welfare over a two-year period. Our empirical results suggest that the lack of private health insurance is a statistically significant and quantitatively important determinant of welfare reentry. Since the vast majority of the terminated families remained off welfare, however, these results suggest the difficulty of meeting the health needs of the employed uninsured. PMID- 2584038 TI - Posthospital needs of elderly people at home: findings from an eight-month follow up study. AB - In a study of 737 elderly hospital patients discharged to their homes in suburban areas northwest of Chicago, Illinois, 60 percent were assessed as needing help with personal care or housekeeping. Only 19 percent were referred by the hospital to community service agencies and, in the immediate postdischarge period, a large proportion of help in both personal care and housekeeping was given by relatives. Eight months after discharge, however, the proportion of care provided by relatives had decreased and the proportion of paid help had increased. The use of help at both points in time was strongly related to limitations in the basic activities of daily living (ADL) at time of hospital discharge. Many patients were unaware of available community services, and 64 percent said that no one in the hospital had talked with them about managing at home. These findings indicate the need for rethinking criteria for hospital discharge planning, more effective communication between service providers and patients, and community focus of attention on elders coming home from the hospital. PMID- 2584039 TI - The extremal quotient in small-area variation analysis. AB - This article reviews the current small-area variation analysis (SAVA) approach to population-based rates of surgery, and describes a new method for ascertaining variance based on the beta-binomial probability distribution of small-area rates. The critical review of the current SAVA approach focuses (1) on how incidence rates are calculated, and (2) on how the significance of the observed magnitude between the largest and smallest rates (i.e., the external quotient) is ascertained. While reducing the problems of calculating rates by considering only certain operative procedures, the new method addresses the current inadequacies of ascertaining significant differences among small areas. Not only does it correctly assess likelihood of an extermal quotient, it also can determine the particular area's rate, producing an unlikely extermal quotient. The method evaluates the probability that the observed magnitude of the extremal quotient is due solely to chance and study design effects, and tables of these probabilities are available for the method's application. A mathematical model, based on a combination of the binomial and beta distributions, uses (1) the sample size, (2) the average of the areas' rates, (3) the variance among the rates, and (4) a specific quotient level to determine the probability of observing the quotient by chance. After computerizing this calculation, probability tables for reasonable values of these four parameters are generated. In addition to looking at just one quotient for each sample, the probability tables facilitate the easy examination of intermediate quotients when the extremal quotient is unlikely due to chance. By alternatively ignoring the highest and lowest rates, two new quotients can be produced and tested. Given that one of these two quotients is likely due to chance, the excluded rate (i.e., producing the unlikely extremal quotient) can be classified as an outliner, and the associated small area should be the focus of more detailed investigation. The probability tables reveal that the external quotient is not the appropriate statistic to be applied in studies where many small areas are to be included. The probability of seeing even a "large" extremal quotient simply by chance rapidly approaches one as the sample size increases. However, an extremal quotient modeled from a beta-binomial distribution can be useful for studies with small sample sizes (e.g., six counties). The use of this beta-binomial model for small-area rates provides a new method of designing and evaluating small-area studies where costs or domain limit the number of areas under consideration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2584040 TI - The effect of arthroscopic surgery of the knee on hospital utilization. AB - Arthroscopic surgery of the knee has reduced in-hospital utilization of 37 percent for surgical treatment of internal derangements of the knee at The Mount Sinai Medical Center. In a study comparing arthrotomies of the knee in 1974 (N = 106) to arthroscopic surgery of the knee in 1984 (N = 221) it was found that while the average patient's age increased 4.39 years to 38.79 years (p less than 0.01) and the number of nonligament knee surgeries increased 108 percent, total annual inpatient hospital days fell to 459 in 1984, from 733 in 1974. The average length of stay in 1984 decreased to 2.07 days, from 6.91 days in 1974 (p less than 0.001). Ambulatory patients comprised 16 percent of the total in 1984, and there were none in 1974. New surgical techniques are reducing in-hospital usage and revenues. Due to the greater third-party reimbursement rate for outpatient operating room use as compared to per diem hospital reimbursement, efficient utilization of ambulatory operating rooms can help to compensate for decreased inpatient census. PMID- 2584041 TI - Men in nursing: their fields of employment, preferred fields of practice, and role strain. AB - A survey of 367 randomly selected male registered nurses (RNs) revealed that (1) they considered certain fields of nursing (e.g., administration, emergency, or intensive care) to be more congruent with the male sex role than other fields (e.g., general medical, outpatient, or obstetrical nursing); (2) they generally preferred work in more congruent fields, except for administration; (3) over time, they were increasingly employed in more congruent fields; and (4) they did not experience significantly less role strain in the more congruent fields of nursing than in the less congruent fields. PMID- 2584042 TI - Myocardial contusion without creatine kinase--MB elevation. AB - Myocardial contusion after chest trauma remains one of the major complexities of trauma care today. Diagnostic methods such as 12-lead electrocardiography and echocardiography, as well as activity of the biochemical marker creatine kinase and the MB subfraction, have not been shown to be sensitive or specific indicators. We report a case of an intraoperatively proved myocardial contusion without creatinine kinase or creatine kinase MB elevation. PMID- 2584043 TI - Lower limb ischemia related to use of the intraaortic balloon pump. AB - In this prospective study we sought to establish the incidence and nature of lower limb ischemia in patients undergoing treatment with intraaortic balloon pump (IABP) counterpulsation and to determine risk factors for its development. The sample was composed of all 258 balloon catheter insertions or attempted insertions for IABP therapy in 249 patients during a 16-month period. Assessment of the lower limbs, hemodynamic status, and pertinent medications were recorded daily throughout the patient's hospitalization. Lower limb ischemia was present in 47%, with 14% having major ischemic complications. Multivariate logistic regression, which was based on variables found to be significant in univariate analysis, revealed that preexisting peripheral vascular disease, female sex, and diabetes mellitus were related to the development of the whole range of lower limb ischemic problems. Diabetes mellitus, cardiogenic shock, and a history of smoking were associated with major ischemia. Evaluation of risks and benefits before treatment with IABP counterpulsation and careful lower limb assessment before, during, and after counterpulsation may help reduce the complications associated with this lifesaving device. PMID- 2584044 TI - Chest wall pain after aortocoronary bypass surgery using internal mammary artery graft: a new pain syndrome? AB - During an 18-month period 11 patients were seen at the Toronto Western Hospital Pain Clinic 4 months to 5 years after internal mammary artery (IMA) bypass with a specific cluster of chest wall symptoms and signs confined to the site of IMA graft harvesting. Sympathetic ganglia blocks produced dramatic but temporary relief of symptoms in two of the most severely affected patients. In two other patients seen quite early after surgery, use of transcutaneous electrical stimulation produced considerable and permanent decrease of symptoms within 3 weeks. Such a chronic pain syndrome has not been previously reported in the literature. We postulate that IMA bypass surgery may be associated with a specific pain syndrome. This syndrome may arise from injury to the anterior branches of the intercostal nerves at the site of graft harvesting. Possible neurophysiologic mechanisms are discussed. PMID- 2584045 TI - Recovery from coma that results as a complication of cardiac arrest followed by cardiopulmonary bypass. AB - Many possible complications are associated with cardiopulmonary bypass. They are similar to the risks accompanying most surgical procedures and include stroke, renal failure, and death. This potential for complication increases when bypass exceeds 2 hours and rises sharply when pump time is prolonged more than 3 to 4 hours. One group of serious complications is major neurologic disorders. The risk of significant cerebral dysfunction, that is, severe focal stroke or coma, is about 1%, and this risk increases with age and coexistent cardiovascular disease. This article focuses on the complication of coma and the possible role cardiopulmonary bypass plays in improving survival rates. A case study is presented illustrating the potential role of cardiopulmonary bypass in the unexpected neurologic recovery from coma. PMID- 2584046 TI - Implications of prosthetic valve implantation: an 8-year follow-up of patients with porcine bioprostheses. AB - Nurses in cardiovascular critical care settings routinely care for patients with implanted valvular prostheses. The presence of an artificial valve substitutes a new disease state for the preexisting valvular disease. Five hundred nine patients who underwent cardiac valve replacement with porcine bioprostheses and who were followed for a total of 1633 patient-years provide the data base for discussion of long-term survival, functional capacity, and morbidity associated with valvular prostheses. Seventy-two percent of patients survived 5 years after operation. New York Heart Association functional class was improved in 84%. Three major types of morbidity were documented: thromboembolism, endocarditis, and valve failure. Cardiovascular nurses should be familiar with the implications of valvular prostheses to provide appropriate patient education and to facilitate the prompt detection and treatment of valve-related complications. PMID- 2584047 TI - Anxiety transmission in the patient with myocardial infarction. AB - The purpose of this study was to examine and document the transmission of anxiety between the family of the patient with cardiac disease and the nurse and between the family and the patient in the coronary care unit (CCU). A nonrandomized sample of 23 patients with an acute myocardial infarction were recruited from two CCUS. An interaction between the CCU nurse and the patient's family member was tape recorded, and immediately thereafter a conversation between the patient and the family member was recorded. Statistical analysis of the data did not support a relationship between the anxiety of the family member and the nurse but did support a positive relationship between the anxiety of the family member and the CCU patient. The study represents a preliminary investigation of the phenomenon of anxiety contagion. PMID- 2584048 TI - Family needs of patients having coronary artery bypass graft surgery during the intraoperative period. AB - The purpose of this study was to describe the needs of the spouses and relatives of patients having coronary artery bypass graft surgery during the intraoperative period. Data were collected in a 434-bed Midwestern hospital from a convenience sample of 23 spouses and 45 adult relatives of 30 patients having their first coronary artery bypass graft operation. Using the Critical Care Family Needs Inventory, subjects were asked to rate the importance of 45 needs. On the basis of item means, the 21 highest-ranked needs were rated as very important or important by both spouses and relatives. Of these top 21 needs, 14 concerned the need for obtaining information. The highest-ranking need for both groups was to have questions answered honestly. Eight needs were identified as significantly more important to spouses than to relatives. Nurses were viewed as the most helpful group in meeting the family's needs. PMID- 2584049 TI - Brain abscess mimicking brain tumor. AB - We review our experience with brain abscesses presenting as primary brain tumor over a 5-year period (1983 to 1988). Four of 66 (6%) patients admitted with the diagnosis of primary brain tumor by computed tomographic scans were found at craniotomy to have brain abscesses. Periapical abscesses found after surgery were determined to be the cause of brain abscess in two of four patients. Our experience suggests that periapical abscess may be a more frequent cause of brain abscess than previously thought, and should be considered before surgery in patients with a suspected brain tumor. PMID- 2584050 TI - Interdisciplinary research. PMID- 2584051 TI - Weal and woe: on the loss of lament. PMID- 2584053 TI - Biological activities of ganglion extracts from a prosobranch mollusc, Fusinus ferrugineus. AB - Acetone extract of the ganglia of Fusinus ferrugineus was applied to C-18 cartridges, and the flowthrough and retained materials were bioassayed on the radula retractor muscle of the animal. The flowthrough was found to have a potent contractile action and the retained material a potent contraction-inhibiting action in addition to a weak contractile action. The retained material was then applied to a column (2.6 x 40 cm) of Sephadex G-15. Fractions of 4 ml each were collected, and their activities were assayed on twitch contractions of the radula retractor. Three peaks (E1, E2 and E3) of contraction-potentiating activity and one peak (I) of contraction-inhibiting activity were obtained. The maximum activities of peaks E1, E2 and E3 were found at fractions 22, 44 and 50, respectively. The maximum activity of peak I was found at fractions 28-30. All of the activities of these peaks were destroyed by incubating the fractions with the peptidase subtilisin, suggesting that the active substances in the peaks are peptides. Using some kinds of molluscan muscles, the actions of the substances were examined in greater detail. The results suggest that peak E1 may contain a novel excitatory peptide whose molecular weight is more than 1,000, and that peaks E2 and E3 may contain FMRFamide-related peptides. It is also suggested that peak I may contain two or more myomodulin-CARP-related inhibitory peptides. PMID- 2584052 TI - Antitumor effect of recombinant human lymphotoxin on a tumor line of human malignant glioma. AB - We examined the antitumor effect of recombinant human lymphotoxin (rHuLT) on a xenotransplantable human malignant glioma line. Tumor-bearing nude mice were treated with rHuLT for three weeks following four schedules: intratumoral injection of rHuLT 20,000 units once a week, twice a week, intravenous injection once a week and twice a week. The inhibition rate of tumor growth was 98.8%, 99.1%, 92.1% and 98.8%, respectively. Histologically, necrotic lesions were observed in the tumors of all treated mice. Thrombo-obstructive changes of tumor vessels were also seen in the tumors of mice after intravenous injection of rHuLT. None of the mice died as a result of this treatment in spite of significant body weight loss. These results indicate that rHuLT has a strong antitumor effect on a xenotransplantable human malignant glioma line. PMID- 2584054 TI - Accurate evaluation of balancing-side contacts in relation to internal derangements of the temporomandibular joint: possible roles of balancing-side protection. AB - Balancing-side contacts were precisely evaluated in relation to internal derangements of the temporomandibular joint. Balancing-side contacts were classified into the three following groups: 1) Severe balancing-side interference, 2) balancing-side interference and 3) balancing-side protective contacts. Balancing-side protective contacts were defined as balancing-side occlusal contacts on lower first and/or second molar in lateral excursive movements, which are observed only when clenching forces are exerted. The prevalence of the balancing-side protection was revealed to be highly correlated with that of internal derangements of temporomandibular joint. These results strongly suggest that balancing-side protection might play an important role as a regulating mechanism in the etiology of internal derangements of temporomandibular joint. PMID- 2584055 TI - Cytogenetical analysis of the human gastric carcinoma cell line TMK-1. AB - We examined a human gastric carcinoma cell line TMK-1 cytogenetically by G banding technique. TMK-1 cells were characterized not only by numerical aberrations but also by structural rearrangements affecting various chromosomes. The modal chromosome number was found to be in the hypotriploid range with most ranging between 64 and 66. Flow cytometry revealed near triploid DNA histogram which was correlated well with chromosome counts. Gain of chromosome 7, 9, 11, and X was found in all of the 25 cells examined and trisomy of chromosome 3, 5, 10, 19, 21 and 22 was also frequently detected. Loss of Y chromosome was shown in all of the cells and monosomy of chromosome 6 and 13 was frequently detected. The most conspicuous rearrangements involved chromosome 6, 12, and 16 which showed complex nonreciprocal translocation. Twenty-two cells (88%) had isochromosome of 12q. A brief review is made of reported karyotype of human gastric cancers. PMID- 2584056 TI - Effects of a diphenyl ether herbicide (CNP emulsion) on mouse fetuses. AB - We investigated the effects of a diphenyl ether herbicide, a chlornitrophen (CNP) emulsion, on mouse fetuses. An MO emulsion was used as the experimental chemical twenty percent of this herbicide consisting of CNP. CNP and other components were extracted and evaporated (undegraded solution). The chemical was diluted 10 times by deionized water and then exposed to sunlight until the CNP concentration in the mixture became 10% of the initial CNP concentration. CNP, degradation products, and other materials were extracted from the mixture and evaporated (degraded solution). The undegraded and degraded solutions were administered subcutaneously to the backs of pregnant mice from the 6th to 15th fetal day, once daily. The mice were sacrificed on the 18th day of pregnancy. The number of fetuses and implantations, their weights, externals and skeletons were observed. Infant mice born from maternal mice treated in the same way as above were weighed once a week. Mean fetal body weights of the undegraded and degraded solution dose groups were significantly lower than those of the control (p less than 0.001). Fetal skeletal abnormalities were also higher than those of the control. The degraded solution dose group differed particularly in this regard from the control (p less than 0.05). In the degraded solution dose group, all 21 newborn infants from two maternal mice out of a total of 43 newborn infants from four maternal mice died within one week. The above results suggest that the degraded solution of CNP is no less noxious on mouse fetuses than the undegraded solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584057 TI - Pentane as an index of in vitro lipid peroxidation via microsomal NADPH-P-450 enzyme systems. AB - Pentane was measured in a mixture of guinea pig liver microsomes and carbontetrachloride (CCl4) in the presence of nicotineamide adenine dinucleotide phosphate (NADPH) and under anaerobic conditions by gas chromatography. Pentane of 0.2 pmol/mg protein/min was formed in the presence of NADPH without CCl4. Pentane formation increased to 2.0 pmol/mg protein/min in the presence of CCl4 and NADPH. This reaction required an anaerobic atmosphere, 2.1 mmol/litter of NADPH and 13.4 mmol/litter of CCl4 under optimal conditions. The formation was reduced in the presence of oxygen, glutathione, vitamin E and metyrapone. These results clearly show that pentane is formed by lipid peroxidation initiated by the free radical cleavage products of CCl4, which are anaerobically produced by NADPH-dependent microsomal enzymes. We conclude that pentane is a good index of in vitro lipid peroxidation via microsomal NADPH-P-450 enzyme systems. PMID- 2584058 TI - Tumorigenicity study of sodium erythorbate administered orally to mice. AB - Sodium erythorbate (SE) was administered at concentrations of 0, 1.25, or 2.5% (maximum tolerated dose, MTD) in the drinking-water to groups of 50 male B6C3F1 mice respectively. Female groups, each consisting of 50 mice, received SE in the drinking-water at concentrations of 0, 2.5 or 5% (MTD). Treatment continued for 96 wks and the experiment was terminated during wk 110. Tumors were observed at various sites including the liver, hematopoietic system, lung and soft tissue. However, at any of the sites, the tumor incidence, the time to death with tumors or the histological distribution of tumors did not differ significantly from those in the untreated control group. Thus, the present study did not demonstrate a tumorigenic effect of SE on B6C3F1 mice by means of oral administration. PMID- 2584059 TI - Prognostic assessment after local resection for the treatment of small carcinoma in lower rectum. AB - Local resection of the lower rectum was performed for the treatment of malignant polypoid lesions in 22 patients. The clinical outcomes of the procedure are summarized as follows; 1. For IIa + IIc type malignant polyp, transanal wedge resection of the entire rectal wall or a transsacral tube resection of the rectum should be performed; as a minimal preventive measure against local recurrence. 2. Early invasive carcinoma (sm) has a metastatic potential on distant organs. 3. In the case of polypoid carcinoma invading the muscle layer (pm), local resection was conducted only in the patients with distant metastasis or with serious complications and in aged patients. 4. When postoperative histological examination reveals a mistake in operative strategy, the patient should be reoperated immediately. PMID- 2584060 TI - Pulmonary lymphangiomyomatosis in childhood? Marked smooth muscle cell proliferation of the lung in a preadolescent girl with repeated pneumothorax and progressive dyspnea. AB - A 13-year-old girl with repeated spontaneous pneumothorax and progressive dyspnea is described. The biopsy specimen of the lung showed marked proliferation of smooth muscle cells in the thickened bullous wall and alveolar septa, which was similar to the findings of the pulmonary lymphangiomyomatosis. Pulmonary lymphangiomyomatosis is one of the diseases which should be considered when children have progressive dyspnea, chylous effusions and repeated spontaneous pneumothorax. PMID- 2584061 TI - Induction of cataract in methylnitrosourea treated Fischer (F344) rats. AB - Cataracts were observed in female F344 rats who intravenously received methylnitrosourea (MNU), a potent carcinogen for multiple organs, in one dose of 50 mg/kg body weight. Induction of cataract 40 weeks after MNU treatment was 41% whereas no cataract was observed in control rats. The aggregation of beta H crystallin fraction by MNU was studied in vitro. HPLC pattern of beta H crystallin changed when lens protein was incubated for 24 hrs with MNU. HPLC patterns indicated that MNU induced high molecular weight aggregates of beta H crystallin. This study conveys some indication about the direct interaction of MNU with lens protein in cataract formation. PMID- 2584062 TI - Prevention of limb ischemia in surgical patients by intra-aortic balloon pumping. AB - Intra-aortic balloon pumping (IABP) was recently performed during the perioperative period in seven patients in whom balloon insertion was difficult because of vascular complication. Prophylactic measures for the prevention of limb ischemia were taken when the balloon was inserted. These measures included (1) balloon insertion through the femoral artery and continuous infusion of heparin into the femoral artery in three patients, (2) balloon insertion through the left femoral artery and femoro-femoral arterial crossover bypass in two patients, and (3) balloon insertion through the left common iliac artery and axillo-femoral bypass on the same side in two patients. Most patients recovered satisfactorily without any evidence of ischemia of the limbs either clinically or in serum biochemistry examination. One patient died of prolonged cardiac failure. PMID- 2584063 TI - Further use of fluorochromes in the cytochemical characterization of phytoplankton. AB - The rapid, specific effects of 25 fluorochromes at low concentration and physiological conditions of pH and temperature were investigated on live cells of five phytoplankton species (Prorocentrum micans, Amphidinium carterae, Dunaliella tertiolecta, Chlamydomonas moewusii and Fragilaria crotonensis). They allowed the identification of cellular components such as the plasma membrane, endoplasmic reticulum, Golgi apparatus, thecal plates, nucleus, mitochondria, trichocysts, vacuoles/lysosomes, polyphosphate and starch granules, lipid bodies and hydrolytic enzymes. Morphological alterations of some of these constituents were examined in cells at different metabolic states. It was found that the thickness of Prorocentrum thecal plates increases during cell development while surface pores appear to be formed in the early stages of thecal formation. The number and size of mitochondria varies among cells at different stages of growth. The number of trichocysts, the size of vacuoles and the quantity of polyphosphates, starch or lipid inclusions increases in nitrogen-depleted cells. Photodegradation and photoenhancement phenomena are described. Some important factors helping to avoid quenching and some applications of the fluorochroming technique are presented. PMID- 2584064 TI - Postnatal development of lectin binding sites in the rat ventral prostate. AB - Five Fluorescein-isothiocyanate (FITC)-labelled lectins were used to study the postnatal development of carbohydrate constituents in the rat ventral prostate: Concanavalin A (Con A), wheat germ agglutinin (WGA), peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA) and Ricinus communis agglutinin I (RCA-I). With all the lectins tested, except RCA-I, specific binding sites could be shown for every stage of differentiation in the glandular epithelium. Binding sites for Con A, WGA, PNA and DBA were found from day 10 to 13 post partum onwards. Each lectin showed a characteristic localization. Binding sites for the lectins used changed to different extents during the following two weeks. After the 24th day post partum no further changes in the lectin binding pattern could be found. The development of the lectin binding properties showed that the changes in carbohydrate-containing constituents of the prostate correlate with the beginning of prostatic secretion and to prostatic epithelial differentiation. In the periacinar stroma the development of the lectin binding pattern was similar to that in the glandular epithelium. The changes of stromal binding sites for Con A and WGA during epithelial differentiation may reflect the changes of epithelial stromal interactions in the prostate. PMID- 2584067 TI - [Relevance of the new tumor marker SCC (squamous cell carcinoma antigen) for the diagnosis and follow-up control of squamous epithelial carcinoma of the head and neck]. AB - The SCC antigen, a tumour marker for squamous cell carcinoma, is already used for the diagnosis and follow-up of carcinoma of the cervix and the lungs. We determined the SCC antigen levels at the time of diagnosis and during therapy in 108 subjects with a squamous cell carcinoma of the head and neck. According to our results and those of other authors, the normal serum range of SCC lies between 0 and 2 ng/ml. Before therapy we found an increased titre in 38.9% of the subjects, being 6.2%, 30.8%, 47.2% and 76.2% for stages T1 to T4 respectively. Thus even some stage T3 and T4 tumours did not express the antigen. No correlation was found between the titre at the time of diagnosis and the grade of differentiation, the site of the tumour, the presence of lymph node or remote metastases, and the sex of the patient. After operation the titres returned to normal within 1 week, but after radiation or chemotherapy the titre decreased more slowly. In recurrent tumours we found a rising titre, which could be measured in several cases some weeks before the recurrence was visible. In the light of the costs and the yield of the method, we suggest determining the serum SCC antigen level once before therapy. If it is increased, subsequent estimates should be done during the succeeding years to allow early diagnosis of a recurrence of the tumour. PMID- 2584065 TI - Human salivary gland glycoconjugates: a lectin histochemical study. AB - The glycoconjugate content of normal salivary glands has been extensively investigated in humans by biochemical means and in non-human mammals by histochemical methods. However, there have been few histochemical studies of human tissues. This paper describes the findings obtained in parotid, submandibular and minor salivary glands by applying a panel of 13 biotinylated lectins, directed against a range of N-linked, fucosylated and galactosylated sequences, using an avidin-peroxidase technique, with appropriate enzymatic and inhibitory sugar controls. The results were generally in accord with those observed in biochemical assays but the use of lectin histochemistry permitted the localization in situ of small amounts of oligosaccharide and, therefore, allowed the recognition of subtle tissue differences. This study expands the current knowledge on the glycoconjugate composition of salivary glands and their lectin histochemistry and serves as a baseline for further studies, particularly in the field of neoplasia. PMID- 2584068 TI - [Treatment of carcinoma of the piriform sinus]. AB - Sixty patients with carcinoma of the piriform fossa were treated with surgery and postoperative irradiation, and 22 other patients with incurable disease were irradiated. All but 2 patients primarily irradiated died within a year. 87% of the 60 patients who were treated by primary surgery had histologically proven lymph node metastases. Twenty six of these patients suffered a local recurrence, regional metastases or distant metastases within 18 months. They were all dead within 2 years of diagnosis of the primary tumor. 75% of patients in this group had shown capsular rupture by metastases. Thirty two of the patients operated on are now free of disease, 23 of them for more than 18 months. Eighteen patients had regional metastases, of whom 6 had caused capsular rupture. The tumor specific 3 year survival was 47.1%. Primary radical surgery followed by radiation therapy is the most effective form of treatment for cancer of the piriform sinus, and should always be advised if possible instead of less mutilating but also less effective forms of treatment. PMID- 2584066 TI - Local cerebral glucose utilization in the hippocampus of old rats. AB - The local cerebral glucose utilization (LCGU) was measured in the different areas and layers of the Ammon's horn and dentate gyrus of young adult (3 to 4-month old) rats, and of 27-month-old rats with proven cognitive deficits. The LCGU was determined by quantitative [14C]2-deoxyglucose autoradiography. Compared to young animals, in the old rats the LCGU was significantly reduced by 12% to 15% in the oriens layers of CA1 and CA2, the pyramidal layers of the CA sectors 1-3, the radiatum and lacunosum-molecular layers of CA2 and CA3 and in the lucidum layer of CA3. The LCGU values of all the other layers of the Ammon's horn and the dentate gyrus did not differ significantly between young and old rats. The pattern of the LCGU reduction found in the old rats roughly resembles changes found after fimbra-fornix lesions or systemic administration of scopolamine, suggesting a functionally important deficit in the cholinergic innervation of the old rats' hippocampi. PMID- 2584069 TI - [Tubal manometry: the question of normal values, values in chronic mesotympanic purulent middle ear infections]. AB - We investigated tubal function by equalization manometry in 68 patients with unilateral traumatic perforation of the tympanic membrane, and in 116 patients with chronic mesotympanic suppuration (85 dry and 31 discharging ears). Our criterion of normal tubal function is the ability to equalize a difference in pressure of +/- 30 hPa by means of at most 7 swallowings. This result was achieved in only 25% of the dry perforations and in none of the patients with discharging ears. Normal tubal function may only be expected in 25% of patients with chronic otitis media. PMID- 2584070 TI - [Manifestations of inactivity in unilateral hearing aid management of patients with a high degree of hearing loss]. AB - Concluding from audiometrical practice using hearing aids unilaterally we could find an inactivity of the unused contralateral ear. We have investigated if it is possible to measure this inactivity by common psychoacoustic methods. We tested 92 persons with advanced combined hearing loss. We had to state that the inactivity is not measurable by mean tone hearing loss according to HAIC (0.5, 1 and 2 kHz), the percentage hearing loss according to Fowler-Sabine, the percentage of hearing loss calculated by speech-audiogram according to Boenninghaus and Roser 1973 and the value of hearing loss for speech (a1). It is only a big discrimination loss that points to the presence of inactivity. The discrimination loss was compared in two groups concerning "used" and "unused" ears. We could clearly measure the biggest discrimination loss in the group of unused ears. The clinical consequences were discussed. PMID- 2584071 TI - [Lateral osteoma--auditory exostosis or hamartoma?]. AB - An osteoma of the external meatus the size of a hazelnut was found in a 30-year old man, arising from the bony edge of the external meatus near the tympanomastoid fissure. Histology showed epithelial cysts, trabeculae, blood forming areas, fat cells, connective tissue and blood vessels. The site of origin and histological findings seem to indicate true hamartoma. PMID- 2584072 TI - Enhanced resolution of the SstI polymorphic variants of the C2 locus: description of a new size class. AB - Investigation of the SstI polymorphism at the 5' region of the gene encoding the serum complement component, C2, in unrelated individuals has been limited by inadequate resolution of the different size variants using conventional agarose gel electrophoresis. We have overcome this problem by the simple modification of electrophoretic conditions using both low current and temperature. With the technique described in this report it has been possible to assign the hetero- and homozygosities of the SstI polymorphism in unrelated individuals without the need for family studies. Using this approach we have investigated a population of 60 healthy, unrelated Caucasians. Five different variants of the SstI polymorphism, the 2.75-, 2.7-, 2.65-, 2.55-, and 2.4-kb fragments, were observed. The 2.7-kb SstI fragment is the most common variant, followed by the 2.65- and the less common 2.4-kb SstI fragments. These fragments occurred at frequencies of 53.3, 35.8, and 7.5%, respectively. We report here a new rare variant of the 2.75- and another rare variant of the 2.55-kb SstI fragments; both occurred at a frequency of 1.7%. The latter variant was previously described as the 2.6-kb SstI fragment but is reclassified in this report as 2.55-kb, based on the results of better resolution on electrophoresis. All the larger-size classes of the SstI polymorphic variants, the 2.75-, 2.7-, and 2.65-kb fragments, are associated with the 4.5-kb TaqI fragment, while the smaller-size classes of 2.55- and 2.4-kb fragments are associated with the 6.6-kb TaqI fragment at the 3' end of the C2 gene. PMID- 2584074 TI - The death of a child: Part II. PMID- 2584073 TI - Genetic origin of human anti-insulin antibodies. AB - Numerous studies have characterized the specificity of human anti-insulin antibodies; however, little is known about their genetic origin. To initiate molecular studies, B cells that bind human insulin were selected from the peripheral blood of diabetic donors and transformed with Epstein-Barr virus. The resulting anti-insulin B-cell lines were cultured at limiting dilution and examined for immunoglobulin heavy-chain gene rearrangements on Southern gels. These studies demonstrated the clonality of the B-cell lines and showed that multiple immunoglobulin heavy chain rearrangements are present. When the heavy chain variable region (VH) gene from one of these Epstein-Barr virus cell lines was cloned, it was found to belong to the recently identified human VHV gene family that represents less than 1% of known human VH genes. Using the polymerase chain reaction, the germline VHV gene of the donor was amplified and sequenced. The sequences showed a high level of homology (98%) between the expressed and germline VHV gene of the donor. While antibodies reactive with autologous insulin (like other autoantibodies) are not extensively mutated from their germline configuration, two replacement substitutions are present in this IgM antibody. PMID- 2584075 TI - The neurologically impaired and dying child: applying the Neuman systems model. PMID- 2584076 TI - Oral-dental concerns of the pediatric oncology patient. AB - One of the main concerns of all disciplines in health care today is maintaining the patient's quality of life and comfort during cancer therapy. Oral complications resulting from radiation or chemotherapy can be expected in a large percentage of patients. Conducting a dental evaluation and performing treatment before therapy can help prevent or lessen potential complications. With preventive care and fewer infections, the patient will be able to communicate with friends and family, and optimum care and comfort can be provided. PMID- 2584077 TI - The emotional and play needs of the dying child. AB - At any particular moment, the doctor's goal is cure and the child's goal is self pleasure. Recreation therapy helps the child meet this goal while moving toward the doctor's goal. When the doctor's goal can no longer be reached, recreation therapy can provide support to the child through the established relationship. The emotional and play needs of the dying child can be met. PMID- 2584078 TI - The spiritual needs of dying children. PMID- 2584079 TI - Educational needs of the terminally ill student. AB - It is the norm for medical professionals to encourage school reentry for the terminally ill student. Their commitment to and belief in the benefits of school involvement are to be commended. It is essential, however, that the hospital staff be directly involved with facilitating school reentry. Research into the needs of chronically and terminally ill students has historically been done by the medical community. Educators lack basic knowledge and the expertise to ensure that the school experience will be successful. It is hoped that the educational community will become more aware and actively seek to guarantee that every child is provided with an appropriate education in future years. For the time being, however, the medical professional must assume the role of coordinator, bringing together the terminally ill child, parents, peers, and educators, and fostering open, ongoing communication between all. The success of these efforts will bring about healthy attitudes toward death and dying; a rich, rewarding experience for all children involved; and ultimately an opportunity for a dying child to live life to its fullest. PMID- 2584080 TI - Families who have a child diagnosed with cancer: what the medical caregiver can do to help them and themselves. PMID- 2584081 TI - Eye movements and blinks: their relationship to higher cognitive processes. AB - Information about the timing of spontaneous eye blinks was abstracted while subjects performed a detection and identification task. We found blinks to be time-locked to saccadic eye movements involved in the identification of peripherally presented stimuli. The larger the required eye movement, the greater the likelihood of blink occurrence. Blink latencies were found to be significantly shorter for centrally, as compared to peripherally presented stimuli, and blinks were more likely to be associated with eye movement returning gaze to a central location than with movements associated with the identification of peripherally presented information. Thus, we conclude that the spontaneous or endogenous eye blink is triggered by aspects of information processing, and that blink latencies can be used as one tool for evaluating the level of complexity of such processing under a wide variety of task demands. PMID- 2584083 TI - Cognitive versus motivational significance of the cardiac response to intense auditory stimulation. AB - This paper reports on an investigation to examine the psychological significance of the heart rate response to intense auditory stimulation--the cardiac defense response (CDR) - by studying its relationship with cognitive tasks related to Lacey's intake/rejection hypothesis (simple reaction time and mental arithmetic) and motivational tasks related to Obrist's cardiosomatic hypothesis (avoidance reaction time and cold pressor). Eight subjects who consistently evoked the CDR pattern (pattern 1) and 8 subjects who consistently did not (pattern 2) underwent the 4 cognitive/motivational tasks balancing the order of task presentation. Results showed that CDR does not bear any relation to mental arithmetic or cold pressor. Significant relationships were found with both simple and avoidance reaction time tasks. During the foreperiod of both tasks, pattern 1 showed a greater initial acceleration followed by a greater final deceleration. In addition, in the avoidance reaction time task pattern 1 showed a greater acceleration after initial greater deceleration during the period prior to the expected shock. It is concluded that CDR is sequentially related to both cognitive processes of input intake (Lacey's hypothesis) and motivational processes of active coping (Obrist's hypothesis). PMID- 2584082 TI - Intensive language learning and increases in rapid eye movement sleep: evidence of a performance factor. AB - Ten anglophone students taking a 6-week French immersion course were recorded in the sleep laboratory during 4 consecutive nights before the course, during the course and after the course. There was a positive and significant (P less than 0.05) correlation between language learning efficiency and increases in the percentage of rapid eye movement (REM) sleep from pre-course to course periods. This observation suggests that learning performance may be an important factor in the relationship between information processing and REM sleep. PMID- 2584084 TI - A modified selective attention auditory event-related potential paradigm suitable for the clinical setting. AB - Auditory event-related potentials (ERPs) were recorded without practice sessions using a selective attention ERP paradigm modified from Hillyard et al. (1973) in 20 normal individuals who varied across wide ranges of age and educational background. The results concur with previous findings concerning the effects of selective attention on both the earlier and later phases of the ERP waveform. Attended stimuli elicited a larger N1 deflection compared with unattended stimuli. Processing negativity was also elicited by attended stimuli, but not by unattended stimuli. Mismatch negativity (N2) was evident in waveforms to signals as compared with standards, and a late positivity (P3) followed N2 only in waveforms to attended signals. This paradigm may be appropriate for evaluating suspected attentional dysfunctions in clinical populations. PMID- 2584085 TI - Specificity of auditory evoked potentials from rat hypothalamus: differential recording by lateral and ventromedial electrodes. AB - Evoked potentials recorded from ventromedial nucleus (VMH) and lateral area (LHA) of the hypothalamus were studied in freely moving rats with respect to specificity of the components to recorded areas and to peripheral stimuli utilized. This study attempts to circumvent some methodological problems and contamination in data with respect to origin of recorded components by comparing monopolar and differential recordings made in VMH and LHA, areas accepted as being involved in food-intake behavior. Of the stable components, the complex with 15-20 ms latency was evaluated as of extra-hypothalamic origin. Meanwhile, those with 25-ms (positive) and 40-ms (negative) average peak latencies were considered as specific to recorded areas. Hypothalamic responses appeared not to be specific to stimulus modality, indicating convergence of different sensory modalities on studied areas. Hunger and satiety appeared to influence the amplitude of the specified components similarly, the study not providing evidence for the reciprocal relation stated in the dual center hypothesis between VMH and LHA. PMID- 2584086 TI - Multivariate EEG power spectral analysis in acute schizophrenics. AB - The electroencephalogram (EEG) during information processing is influenced by specific changes in brain electrical activity. Based on the theory of disturbed information processing in schizophrenics, we analysed auditory stimulus induced EEG changes by Fast Fourier Transformation. The most important of the significant stimulation-dependent EEG power changes were measured in the 0.5-3.5 Hz and 10 13.5 Hz frequency bands in the left frontoparietal lead. In a multivariate analysis the separation of the subjects examined into acute schizophrenics and normals was incorrect in only 21% of the cases (resubstitution rate); using pi method an error of 31% was estimated. PMID- 2584087 TI - We do remember our humanity. PMID- 2584088 TI - Psychophysiological micromapping of the human brain. AB - Neuronal impulse activity (NIA) of cortex and subcortical nuclei of the brain was studied in patients diagnosed and treated with the aid of long-term intracerebral electrodes. A special battery of psychophysiological tests was constructed for study of reflexion of different mental functions in NIA, such as various speech functions, short-term and long-term memory, count and arithmetic operations, emotions. Neuronal populations with the significant responses have been revealed during these testings. First results of psychophysiological mapping of the human brain obtained from NIA data have been presented. PMID- 2584089 TI - Feedback EEG in the detection of subclinical hepatic encephalopathy: a preliminary report. AB - The detection, monitoring, and quantification of subclinical hepatic encephalopathy present difficult problems for the clinician caring for patients with liver disease. Traditionally, pencil and paper tests such as signature writing have been used at the bed-side to measure early encephalopathy. More recently, the Trail-making test has been employed to detect and quantify encephalopathic changes. While the electroencephalogram has provided information about the extent of clinically-obvious encephalopathy, it has only recently proved useful in the detection of subclinical disease. In these cases, evoked potentials and spectral analysis methods have discriminated between 35 and 62% of patients with subclinical hepatic encephalopathy. The present study used the method of feedback electroencephalography to detect and quantify differences in cortical arousal in 5 cirrhotic patients and 5 normal age-matched controls. Subject were also compared with respect to baseline measures of cortical arousal. Finally, arousal during feedback EEG stimulation was correlated with Trail-making test performance. The data revealed that cirrhotic patients can be discriminated from normal controls by baseline (80% detection) and feedback stimulation conditions (100% detection). In addition, feedback EEG reactivity (cortical arousal) was inversely correlated with Trail-making test performance (-0.86, P less than 0.01). The results indicate that simple features of the conventional EEG can reliably discriminate cirrhotic patients from normals. Clinical application of the feedback method in other metabolic encephalopathies, as well as in hypoaroused states secondary to, for example, narcolepsy, is discussed. PMID- 2584090 TI - ERP study of the development of the holistic and analytic modes of processing between 6 and 8 years. AB - Event-related potentials (ERPs) were recorded (01, 02, Fcz, Cpz leads) from 32 normal children aged from 6 to 8 years during a categorisation task performed with 4 types of stimuli that allowed for a holistic and/or an analytic development to modify information processing according to the child's age. Whatever age, derivation or stimulus, the individual ERPs showed a large negative N2 wave (mean latency: 230 ms) made up of two widely overlapping components. In order to separate these components, an initial principal component analysis (PCA) was performed on the waveforms; this PCA provided a principal component that accounted for the amplitude difference between the first negative peak of the N2 wave (180 ms after stimulus onset) and the subsequent slope change. A second PCA was then carried out on the corresponding individual component scores; this second PCA provided two factors according to whether the stimuli were holistically or analytically processed. Regarding the pre- and post-vertex data (Fcz and Cpz), these two factors accounted for the same ERP effect for the 6-year old children but opposite effects after the age of seven. We interpreted this change as reflecting the differentiation of specific - holistic and analytic - modes of processing from a non-specific mode after the establishment of the concrete operation period. PMID- 2584091 TI - Effect of acute respiratory acidosis on multimodality sensory evoked potentials of Long-Evans rats. AB - Auditory, visual and somatosensory evoked potentials (EPs), recorded epidurally from 31 chronically implanted male Long-Evans rats, were studied to examine the pattern of sensory effects caused by hypercapnia. Recordings were obtained before exposures, 10-20 min after the beginning of exposure to CO2 in synthetic air, and 30 min after the end of exposure. Previous recordings revealed no substantial effects of the extended recording period itself. Blood pH during an average exposure of 18.8% CO2 was about 7.1. During this level of CO2 exposure the somatosensory response was almost completely abolished, but the latencies of early detectable components were not affected. In contrast, the latencies of all brainstem auditory evoked response components and the 1-5 interwave time increased, whereas amplitudes were only slightly affected. Amplitudes and latencies of early and late components of the flash EP were decreased and lengthened, but the after-discharge components appeared to be most sensitive to CO2. Concentration-response relationships were examined by exposure of rats to 8 and 16% CO2. The most sensitive EP parameter was average amplitude of the late somatosensory EP components. These results suggest that EPs might be useful for assessing acute metabolic disturbances as well as more commonly assessed neurologic disorders. PMID- 2584092 TI - Hemisphere asymmetry of alpha burst sequential organization in depression. AB - A new quantitative EEG index based on the sequential variability of the frequency of occurrence of alpha bursts (alpha-BVI) was utilized for investigating the respective role of the two hemispheres in depression and their relationship with two clinical dimensions of this illness: psychomotor retardation and blunted affect. The EEG (at P3 and P4 referred to Fz) was recorded during rest periods in two groups of patients selected according to their scores on various clinical scales: one consisted of 12 patients characterized by psychomotor retardation (PMR group), the other of 9 patients characterized by blunted affect (BA group). A control group of 12 normal subjects was recorded in the same conditions. All subjects were dextral. The following main results were obtained: (1) in both groups of patients the right and the left alpha-BVI were, before treatment, significantly lower than those of the controls. (2) In controls, the sequential alpha burst variability was identical on both hemispheres. (3) In patients, before treatment, the right hemisphere alpha-BVI was significantly lower than the left. (4) Electro-clinical correlations were also observed: (A) in the BA group, before treatment, (a) between the degree of blunted affect and the decrease of the right alpha-BVI, (b) between ideoverbal retardation and the decrease of the left alpha-BVI (these correlations disappeared after treatment); (B) in the PMR group, ideoverbal retardation was, on the contrary, correlated to a right alpha BVI decrease, this correlation persisting after treatment. These results are discussed according to the role of each hemisphere in depression. PMID- 2584093 TI - Event-related potential evidence of semantic mismatch in a 'same-different' reaction time task. AB - In a 'same-different' reaction time (RT) task, suit (spades and/or hearts) target stimuli, and irrelevant suits (distractors) or plus signs (indifferent elements) were presented. The 'same' RT was shorter than the 'different' RT. This 'fast same' effect was independent of the RT increase caused by the distractor stimuli. Event-related potentials (ERPs) in trials with distractor elements were more negative in the 350-600 ms latency range than the ERPs of trials with different irrelevant elements. PMID- 2584094 TI - The problem of cardiac response latency-jitter and plethysmographic recording: a reply to Barry and Mitchell. PMID- 2584095 TI - Electrocardiogram and pulse-derived phasic cardiac responses: a rejoinder to Turpin. PMID- 2584096 TI - FDA sponsors symposium on proper animal drug use. PMID- 2584097 TI - The Pew Report and the food animal practitioner. PMID- 2584098 TI - The well-informed veterinarian. PMID- 2584099 TI - Survey of intradermal skin testing practices in North America. AB - Allergic skin diseases are commonly diagnosed by veterinarians. Inhalant-related allergic diseases are especially prevalent in companion animal species. Intradermal skin testing (IDST) is the usual method for diagnosis of these syndromes, and is often followed by hyposensitization treatment if an animal reacts to substances during testing. A mail survey of veterinarians in the United States and Canada was conducted to determine current procedures in use for IDST and opinions on results of IDST and hyposensitization. Results of the survey indicate that IDST procedures are not currently standardized and that there is wide variation in the methods used. Opinion regarding results of skin testing and hyposensitization was largely in agreement with previously published patient studies. PMID- 2584100 TI - Antebrachial metacarpal arthrodesis for fusion of deranged carpal joints in two dogs. AB - Congenital malformation of the carpal joint in a young dog resulted in a progressive lameness. Traumatic disruption of the carpus in another dog resulted in carpal bone necrosis, infection, and chronic instability. Radial metacarpal arthrodesis was performed in both dogs. The diseased carpal bones were excised, sparing the accessory carpal bone in both dogs. Radial metacarpal arthrodeses were then performed, using bone plate fixation. In the dog with the malformed limb, the gait had improved, but intermittent lameness was still present 8 months later because of an associated malarticulation of the cubital joint. The dog with the traumatized carpus had little or no lameness associated with normal activity for 32 months. PMID- 2584101 TI - Fractured capital femoral epiphysis in twin ewes. AB - Capital femoral physeal fractures occurred simultaneously in twin 2-year-old Shropshire ewes. The fractures resulted in gradual, progressive lameness and recumbency. There was no history of trauma and no other ewes in the flock were affected. The fractures occurred at an age when the capital physis should have been closed. Clinical and postmortem examination of the ewes and evaluation of the ration did not reveal predisposing factors for the condition. A familial tendency for fractured capital femoral epiphysis is well documented in human beings, but there is no known familial tendency in sheep. PMID- 2584103 TI - Cervical hyperplasia with prolapse in a mare. AB - Cervical hyperplasia with prolapse through the vulvar lips was documented in a mare. Postmortem examination indicated that the mass originated from the cervical wall. The surface of the prolapsed mass had histologic features of normal cervix. Cervical hyperplasia can be considered in a list of differential diagnoses in cases of prolapse of the internal genitalia in mares. PMID- 2584102 TI - Internal fixation of a transverse scapular neck fracture in a filly. AB - A 3-week-old Standardbred filly had a non-weightbearing forelimb lameness caused by scapular neck fracture. The fracture was repaired with 2 dynamic compression plates placed 90 degrees to each other. A 10-hole 4.5-mm narrow dynamic compression plate was placed on the cranial aspect of the scapular spine, and a 10-hole 3.5-mm dynamic compression plate was placed caudal to the scapular spine. One year after surgery, the filly was not lame when exercising in the pasture, and muscle atrophy was not evident on the affected limb. Eighteen months after surgery, the filly was in race training with no apparent problems caused by fracture repair. PMID- 2584104 TI - Staphylectomy for treatment of dorsal displacement of the soft palate in two foals. AB - Dorsal displacement of the soft palate associated with dysphagia and aspiration pneumonia was diagnosed in 2 young foals. The displacement appeared to be congenital. Clinical signs associated with the condition were resolved after staphylectomy. Dorsal displacement of the soft palate is usually recognized in adult animals as an upper respiratory tract disease, but may be a contributing factor to dysphagia and lower respiratory tract disease in young animals. PMID- 2584105 TI - Evaluation of cisplatin-induced emesis in dogs with malignant neoplasia: 115 cases (1984-1987). AB - A retrospective review of the records of 115 dogs with 13 types of malignant tumors was performed in an attempt to identify factors that influence the degree of emesis observed within 24 hours after cisplatin therapy. Six groups were established on the basis of dosage of cisplatin and on the route of administration: 10 mg/m2 IV (n = 17), 40 mg/m2 IV (n = 10), 50 mg/m2 IV (n = 19), 60 mg/m2 IV (n = 7), 70 mg/m2 IV (n = 36), and 70 mg/m2 intra-arterially (IA; n = 26). Age, gender, weight, dose of cisplatin, route of administration (IV vs IA), and duration of infusion were evaluated. Increasing doses of cisplatin (P less than 0.01) and the IV route of drug administration (P less than 0.0006) were associated with an increased occurrence of vomiting in response to the first treatment. Anesthesia, performed in dogs that were given cisplatin IA, was a confounding variable that may have reduced the emetic potential of the drug after the dogs were awakened. If the dog vomited in response to the first treatment, there was a greater tendency to vomit after subsequent cisplatin treatments (P = 0.08). Multivariable analysis, after correcting for the effects of age, gender, and weight, indicated that high doses of cisplatin (P less than 0.001) and lower weight of the dog (P less than 0.04) were significantly associated with an increased likelihood of vomiting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584106 TI - Mesenteric torsion in dogs with exocrine pancreatic insufficiency: 21 cases (1978 1987). AB - Mesenteric torsion was diagnosed in 21 of 199 German Shepherd Dogs suffering from exocrine pancreatic insufficiency. Eight dogs were euthanatized at the request of the owners; 4 dogs died at home before any treatment for mesenteric torsion was initiated. Surgery was performed on 9 dogs, all of which died during recovery from anesthesia. PMID- 2584107 TI - Employment, starting salaries, and educational indebtedness of 1989 graduates of US veterinary medical colleges. PMID- 2584108 TI - Comments on use of 4-methylpyrazole. PMID- 2584109 TI - Observations on flea bite allergic dermatitis. PMID- 2584110 TI - Identifying with the profession. PMID- 2584112 TI - The previous veterinarian. PMID- 2584111 TI - Right to life--the sparring continues. PMID- 2584113 TI - Could an apple a day be harmful to your health? PMID- 2584114 TI - Study takes aim at lowering risks of cancer, heart disease. PMID- 2584115 TI - Rabies vaccine initiative gets booster from public health veterinarians. PMID- 2584116 TI - Echinococcosis (hydatid disease). PMID- 2584117 TI - Recent malpractice decisions of importance to veterinarians. PMID- 2584118 TI - ECG of the month. Paroxysmal ventricular tachycardia in a horse with diarrhea. PMID- 2584119 TI - Comparison of bacteria isolated from specimens obtained by use of endoscopic guarded tracheal swabbing and percutaneous tracheal aspiration in horses. AB - Results of bacteriologic culture of specimens obtained from 14 horses with pneumonia and from 15 horses that were clinically healthy (nonpneumonia group) were compared. Specimens were obtained by use of an endoscopic guarded tracheal swabbing method and percutaneous tracheal aspiration. The percentage of agreement between the 2 tracheal specimens for the horses of the pneumonia group was 79% for aerobic isolates and 100% for anaerobic isolates. The percentage of agreement between results of the 2 tracheal specimens for horses of the nonpneumonia group was 80% for aerobic organisms and 93% for anaerobic organisms. The endoscopic guarded swabbing method described here for obtaining specimens from the lower airways for bacteriologic culture did not always prevent contamination. Results of the study suggested that this endoscopic swabbing technique has merit and should be considered as an alternative to the tracheal aspiration method. Pseudomonas sp and any anaerobic bacteria that are isolated must be viewed as potential contaminants of the endoscopic swab specimen and may not be involved in the primary pulmonary disease. PMID- 2584121 TI - Treatment of serous retinal detachments associated with optic disk pits in dogs. AB - Serous retinal detachment, associated with optic disk pit, was diagnosed in 28 eyes of 24 dogs. Xenon arc photocoagulation was used in treatment of the detachment. Of 24 dogs, 21 were Collies. In 23 eyes, retinal detachments affected temporal and/or inferior portions of the retina. In 5 eyes, detachments were predominantly superior and/or nasal. A single photocoagulation treatment resulted in reattachments in 25 eyes. Of the 3 remaining detachments, 2 eyes improved with additional photocoagulation, and 1 eye, which was not treated further, had a complete retinal detachment. PMID- 2584120 TI - Frequencies of feline blood groups in the United States. AB - A survey of AB blood group frequencies among cats in the United States was undertaken, using feline blood typing reagents from Australia. We typed blood of 280 cats of both genders and various breeds within the Philadelphia area and 205 cats at 27 veterinary medical teaching hospitals (most cats had been used as blood donors in 1987) throughout the United States. All but 2 cats had type-A blood. A Himalayan cat in Philadelphia and a domestic shorthair cat from Florida, neither of which had been used as a blood donor, had type-B blood. Plasma of the 2 blood-group-Bcats contained strong isoagglutinins (greater than 1:8 titer) against type-A cells, thereby allowing their detection in a major cross-match test. Approximately 30% of tested plasma samples from blood-group-A cats had weak isoagglutinins (1:2 titer) against type-B cells. This limited survey suggests that cats in the United States, including blood donors, predominantly have type-A blood, and that blood-group-B cats are rare. PMID- 2584122 TI - Chronic dilatative myocarditis caused by Trypanosoma cruzi in two dogs. AB - Trypanosoma cruzi was believed responsible for causing chronic dilatative myocarditis in 2 female hunting dogs. Clinical signs included ascites, respiratory distress, thoracic effusion, cyanosis, and weak pulse with ventricular arrhythmias. Electrocardiography indicated first-degree heart block, chamber enlargement, and ventricular-based arrhythmias unresponsive to treatment. M-mode echocardiography of 1 dog confirmed bilateral cardiac enlargement and septal and left ventricular free wall thinning. Multifocal infiltrates of plasma cells, lymphocytes, and histiocytes, cardiocyte degeneration, and multifocal fibrosis were the predominant histologic lesions. Trypanosoma cruzi pseudocysts were infrequently found. PMID- 2584123 TI - Lymphosarcoma with disseminated skeletal involvement in a pup. AB - Lymphoblastic lymphosarcoma with disseminated skeletal involvement was diagnosed in a 15-week-old Golden Retriever. The skeletal disease was characterized by diffuse, irregular areas of radiolucency most evident in the diaphyseal portion of long bones and was associated with gait abnormalities and signs of pain. Necropsy also revealed involvement of the spleen, liver, kidneys, and mesenteric lymph nodes. PMID- 2584124 TI - Clinical, echocardiographic, and radiographic findings of peritoneopericardial diaphragmatic hernia in two dogs and a cat. AB - Peritoneopericardial diaphragmatic hernia was diagnosed in 2 dogs and a cat. One dog was referred because of clinical signs of cardiac tamponade and acute decompensation from liver entrapment within the hernia. Surgical correction of the hernia alleviated clinical signs in all 3 animals. Echocardiography was used in combination with radiography to provide a rapid and accurate diagnosis. PMID- 2584126 TI - Atypical contagious ecthyma in a sheep after extensive cutaneous thermal injury. AB - An atypical case of contagious ecthyma in a wether, following severe thermal injury to the skin, is reported. Histologically, extensive verrucous growths at the edges of the burned skin were areas of severe epidermal hyperplasia and hyperkeratosis. Intracellular viral particles were present, and sections of skin were positive for ovine contagious ecthyma virus by a fluorescent antibody test. PMID- 2584125 TI - Orbital neoplasia with enophthalmos in a cat. AB - A 9-year-old cat was evaluated for left-sided enophthalmos and protrusion of the third eyelid. A primary orbital fibrosarcoma was diagnosed. During the orbital exploration, normal periorbital fascia could not be identified in the lateral and ventral region, thus accounting for the enophthalmos. PMID- 2584127 TI - Fracture repair with transfixation pins and fiberglass cast in llamas and small ruminants. AB - Transfixation pinning with fiberglass casting is an effective and adaptable method of longbone fracture fixation in llamas and small ruminants. Treatment of fractures in 7 limbs of 4 llamas and 2 small ruminants with this technique are described. Steinmann pins are placed transcortically proximal, and if necessary, distal to the fracture. The pin ends and limb are encased in fiberglass cast material. The cast is strong enough in animals of this size to eliminate the need for external frames or connecting bars. Severely comminuted fractures and fractures near joints are especially suited to fixation with this technique. Complications encountered in these cases included loosening of pins and one delayed union. All fractures healed to permit full use of the limb. PMID- 2584128 TI - Peritoneal dialysis in dogs and cats: 27 cases (1976-1987). AB - The records of 25 dogs and 2 cats treated with peritoneal dialysis during an 11 year period were evaluated. The indications for peritoneal dialysis were acute renal failure in 21 animals, chronic renal failure in 5 animals, and azotemia of undetermined cause in 1 animal. Peritoneal dialysis resulted in a significant (P less than 0.05) decrease in serum urea nitrogen concentration in 19 of the dogs and a significant (P less than 0.05) decrease in serum creatinine in 20 dogs. The most common complication of peritoneal dialysis was hypoalbuminemia (11 animals affected). Other common complications were dialysate retention/catheter obstruction (8 animals), peritonitis (6 animals), hypochloremia (6 animals), and subcutaneous leakage of dialysate (6 animals). Twelve dogs and 2 cats died during treatment, 6 dogs were euthanatized, and 1 dog was lost to follow-up evaluation. The remaining 6 dogs survived and were discharged from the hospital after successful peritoneal dialysis. On the basis of the results of this study, the authors concluded that peritoneal dialysis, although associated with a high complication rate, was a successful technique for reducing azotemia in dogs with acute and chronic renal failure. Survival rates were poor because of the severity of the underlying renal diseases. PMID- 2584129 TI - Complications of transposition of the fibular head for stabilization of the cranial cruciate-deficient stifle in dogs: 80 cases (1982-1986). AB - Over a 5-year period, fibular head transposition was performed in 85 stifles in 80 dogs with rupture of a cranial cruciate ligament. The most common complication during surgery was iatrogenic fracture of the fibular head or neck (10 dogs; 12.5%), and the most common postoperative complication was seroma formation at the lateral aspect of the proximal portion of the tibia overlying the pin (6 dogs; 7.5%). Sixty-nine of 80 owners were contacted for follow-up evaluation of lameness 6 months to 5 years after surgery; 51% reported excellent results, 39% good results, and 10% fair results. Fifty-six dogs were available for long-term follow-up examination; all dogs had some degree of medical thickening of the stifle, 27 (48%) had crepitus, 4 (7%) had signs of pain, and 2 (3.5%) had moderate cranial drawer instability on manipulation of the joint. Results were good or excellent in 90% of the dogs. PMID- 2584130 TI - What is your diagnosis? Fusion of the ulnar and fourth carpal bones. PMID- 2584131 TI - Accreditation in the allied health professions. AB - Specialized accreditation in the allied health professions can and will fulfill its basic purpose if its efforts are guided by the principle that evaluation must place its emphasis on the outcome of the educational process, no matter how difficult it may be to assess. This requires the commitment and cooperation of both the accrediting body and the institution and program under review. Accreditation is a vitally important and valuable system in higher education in general, and the allied health professions are no exception. If the system is to be effective, however, every temptation must be resisted by all involved parties to debase it by using it for self-serving purposes. A recognized accrediting agency not only has the right, but indeed the responsibility, to ensure that the graduates of a program under review possess the prerequisite knowledge and skills essential for entrance into a given allied health profession. In cases where that minimal standard is not attained, the program should be required to remove those deficiencies in a timely manner or, if sufficiently serious, have its accreditation withheld or withdrawn. There should be no exceptions to this course of action. Every standard or essential adopted should be defensible on sound educational grounds, and every program should be evaluated according to whether it is in compliance. Accrediting bodies must direct their efforts toward evaluating educational quality. They must respect institutional rights and responsibilities and not even attempt to prescribe what will be taught or by whom, or who will administer a given program. The entire accreditation process must account for institutional diversity and should not discourage experimentation, innovation, or modernization. However, the standards and essentials that are ultimately adopted must be applied uniformly and fairly and not in an arbitrary or capricious manner. Hence, it is imperative that the standards and essentials be stated in such a way that they are clear and understandable. For those programs in which an enhancement or upgrading is deemed necessary for one or more aspects of the educational experience, it would be a genuine service to the institution and its consistuency if the accrediting agency could offer sound advice and suggestions for remedying those factors that may be causing or contributing to the observed deficiencies in the educational outcome. Any responsible institution would welcome such an approach, and the outcome should be an upgrading of the program under review with a concomitant enhancement of the profession involved.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2584132 TI - An integrated team approach to the management of patients with oropharyngeal dysphagia. AB - This paper describes a team approach to the assessment and management of patients with oropharyngeal dysphagia of neurologic origin. The team's major focus was to determine the need for adjustments to the patient's diet to maintain or restore the safety of oral feeding. This involved the development of a detailed radiographic examination and a series of dysphagia diets, in addition to comprehensive evaluations by an occupational therapist, physiotherapist, and speech pathologist. The effects of deteriorating swallowing ability on the physical, cognitive, and emotional status of the patient are discussed in the context of a multidisciplinary approach. PMID- 2584133 TI - A view from Washington. PMID- 2584134 TI - Novel antifungal antibiotics maniwamycins A and B. I. Taxonomy of the producing organism, fermentation, isolation, physico-chemical properties and biological properties. AB - Two antifungal antibiotics maniwamycins A and B were isolated from the culture broth of a strain of actinomycetes, which were classified as Streptomyces prasinopilosus. These antibiotics were isolated by resin absorption and extraction with EtOAc and purified by column chromatography. Both antibiotics were found to be new azoxy substances from their physico-chemical properties. They showed broad antifungal spectra. PMID- 2584135 TI - Novel antifungal antibiotics maniwamycins A and B. II. Structure determination. AB - The structures of the new azoxy antibiotics maniwamycins A and B have been determined by means of spectral analyses and chemical studies. PMID- 2584136 TI - AT2433-A1, AT2433-A2, AT2433-B1, and AT2433-B2 novel antitumor antibiotic compounds produced by Actinomadura melliaura. Taxonomy, fermentation, isolation and biological properties. AB - Compounds AT2433-A1 (A1), AT2433-A2 (A2), AT2433-B1 (B1), and AT2433-B2 (B2) were isolated from the cultured broth of Actinomadura melliaura sp. nov. (SCC 1655). Structurally these materials are closely related to rebeccamycin (1), an indolocarbazole antitumor antibiotic. A1, A2, B1, and B2 were active against Staphylococcus aureus A9537, Streptococcus faecalis A20688, Streptococcus faecium (ATCC 9790), Micrococcus lutea (ATCC 9341), Bacillus subtilis (ATCC 6633). A1 and B1 were active against P388 leukemia in mice. PMID- 2584138 TI - Altemicidin, a new acaricidal and antitumor substance. II. Structure determination. AB - The structure of altemicidin, a new acaricidal and antitumor agent, was determined to be (1R,2S,3aR,7aS)-4-carbamoyl-2-hydroxy-6-methyl-1-(sulfamo ylacetamido)-2,3,3a,6, 7,7a-hexahydro-6-azaindene-1-carboxylic acid by a combination of spectroscopic and X-ray crystallographic analysis of its derivatives. Altemicidin is a monoterpene alkaloid. PMID- 2584137 TI - Altemicidin, a new acaricidal and antitumor substance. I. Taxonomy, fermentation, isolation and physico-chemical and biological properties. AB - Screening of new insecticidal and acaricidal antibiotics was carried out with reference to anti-brine shrimp activity from actinomycete strains isolated from marine environments. Of 200 actinomycete isolates, one isolate was found to produce a new substance, altemicidin. The strain was isolated from sea mud collected at Gamo, Miyagi Prefecture, Japan, and identified as Streptomyces sioyaensis SA-1758. Altemicidin was purified by Diaion CHP-20P and Sephadex LH-20 column chromatographies. The molecular formula was determined as C13H20N4O7S by elemental analysis, MS and 13C NMR spectrum. Altemicidin showed not only acaricidal activity but also antitumor activity. The compound showed no antimicrobial activity except the inhibitory activity to Xanthomonas strains. PMID- 2584139 TI - Maggiemycin and anhydromaggiemycin: two novel anthracyclinone antitumor antibiotics. Isolation, structures, partial synthesis and biological properties. AB - Two new anthracyclinone antitumor antibiotics, maggiemycin (6, NSC-D344012) and anhydromaggiemycin (8) have been isolated from a culture of an unspeciated Streptomyces (ATCC No. 39235). Bioautography against Bacillus subtilis was used for the preliminary detection of these anthracyclinones. Structures were proposed based on their UV-visible, IR, 1H NMR, 13C NMR spectra, electron impact (EI) and high-resolution EI-MS and confirmed by partial synthesis and a direct correlation with epsilon-rhodomycinone. Both the anthracyclinones are active against KB, P388 and L1210 murine tumor cell lines; however, anhydromaggiemycin was more active than maggiemycin. A number of related anthracyclinones have also been prepared and their biological activity has been determined. The structure-activity relationship of these new anthracyclinones is also discussed. PMID- 2584140 TI - FK409, a novel vasodilator isolated from the acid-treated fermentation broth of Streptomyces griseosporeus. I. Taxonomy, fermentation, isolation, and physico chemical and biological characteristics. AB - FK409, a novel vasodilator with anti-platelet aggregation activity, has been isolated from the acid-treated fermentation broth of Streptomyces griseosporeus No. 16917, which was cultured on a medium containing NaNO3 for 4 days. FK409 was purified from the culture-filtrate by extraction with ethyl acetate after adjusting the pH to 3.0 with HC1, followed by silica gel chromatography. The molecular formula of this compound was determined to be C8H13N3O4. In vitro, FK409 showed a potent relaxation activity on noradrenaline induced contraction of rat aorta. In addition to the vasodilating activity, this compound also showed potent anti-aggregation activities towards rabbit platelets. In vivo, intravenously administered FK409 resulted in marked blood pressure lowering in rats. PMID- 2584141 TI - FK409, a novel vasodilator isolated from the acid-treated fermentation broth of Streptomyces griseosporeus. II. Structure of FK409 and its precursor FR-900411. AB - In a purification study of novel vasodilator FK409 from the fermentation broth of Streptomyces griseosporeus, we found the existence of FR-900411, a precursor of FK409 in the broth, suggesting that FK409 was derived from FR-900411 via a chemical reaction. We therefore isolated FR-900411 from the broth. The structure of FK409 and FR-900411 were determined to be 1 and 2 respectively, on the basis of spectroscopic and chemical evidence. PMID- 2584142 TI - FK409, a novel vasodilator isolated from the acid-treated fermentation broth of Streptomyces griseosporeus. III. Reaction mechanism and synthesis. AB - FK409 (1), a novel vasodilator, is a semi-artificial fermentation product of Streptomyces griseosporeus No. 16917, which was cultured in a medium containing nitrate. And the acid-treatment of the broth is essential for the generation of FK409. FK409 was considered to be formed via a novel synchronous nitrosation nitration reaction of FR-900411 (2) which was produced by the strain as a precursor of FK409. The conversion of FK-900411 to FK409 proceeded under acidic conditions with nitrite formed by microbial reduction of nitrate. Total synthesis of FK409 was achieved starting from (E)-2-ethyl-2-butenal (3) via a nitrosation reaction of FR-900411 (2) as a key step. PMID- 2584143 TI - A novel series of milbemycin antibiotics from Streptomyces strain E225. I. Discovery, fermentation and anthelmintic activity. AB - A novel series of milbemycin antibiotics were produced by soil isolate, strain E225 which was shown to be a Streptomyces species. The antibiotics displayed anthelmintic activity against Trichostrongylus colubriformis in the gerbil. Two of the compounds, VM 44857 and VM 44866 were shown to be potent anthelmintics against mixed nematode infections in sheep. PMID- 2584144 TI - Epiderstatin, a new inhibitor of the mitogenic activity induced by epidermal growth factor. I. Taxonomy, fermentation, isolation and characterization. AB - Inhibitors of mitogenic activity induced by epidermal growth factor (EGF) were screened from culture broths of soil microorganisms. A strain of actinomycetes has been found to produce a new glutarimide antibiotic named epiderstatin which inhibits the incorporation of [3H]thymidine into quiescent animal cells stimulated by EGF. Taxonomic studies have revealed that the producing strain belongs to a subspecies of Streptomyces pulveraceus, thus the name, Streptomyces pulveraceus subsp. epiderstagenes was given to this strain. The molecular formula (C15H20N2O4) and UV profile (lambda max 295 nm) of the antibiotic are distinct from other known antibiotics. It inhibited the incorporation of [3H]thymidine into quiescent cells stronger than into growing cells. PMID- 2584145 TI - UK-69,753, a novel member of the efrotomycin family of antibiotics. II. Structure determination and biological activity. AB - A novel antibiotic, UK-69,753, has been isolated from a submerged fermentation of Amycolatopsis orientalis strain N731-15. UK-69,753 has been assigned the structure 1 using spectroscopic means, primarily by NMR analysis. UK-69,753 is a glycoside of factumycin (A40A), a previously reported member of a small group of antibiotics related to aurodox and efrotomycin. UK-69,753 was shown to have potent activity both in vitro and in vivo against the swine pathogen Treponema hyodysenteriae. PMID- 2584146 TI - The structure of vacidin A, an aromatic heptaene macrolide antibiotic. I. Complete assignment of the 1H NMR spectrum and geometry of the polyene chromophore. AB - The constitution of vacidin A, a representative of the aromatic heptaene macrolide antibiotics was established on the basis of 13C and 1H-1H double quantum filtered correlated spectroscopy, rotating frame nuclear Overhauser effect spectroscopy, J-resolved 1H as well as 1H-13C correlation NMR spectra. Geometry of the polyene chromophore was determined as 22E,24E,26E,28Z,30Z,32E,34E. PMID- 2584147 TI - The structure of vacidin A, an aromatic heptaene macrolide antibiotic. II. Stereochemistry of the antibiotic. AB - On the basis of coupling constants and rotating frame nuclear Overhauser effect spectroscopy of vacidin A methoxycarbonylmethylamide, the stereochemistry of the antibiotic was established. The configuration of the aglycone was determined as (3R,7R,9R,11S,13S,15R,17S,18R,19S,21R, 36S,37R,38S). The aminosugar constituent of the antibiotic was identified as beta-(D)-mycosamine. The chiral center at C 41 remains to be assigned. PMID- 2584149 TI - Reexamination of the 1H and 13C NMR spectral assignments of thiostrepton. AB - The use of 2D NMR techniques on unlabeled and biosynthetically multiple 13C labeled samples enabled us to refine the 1H and 13C NMR spectral assignments for thiostrepton. PMID- 2584148 TI - 1H and 13C NMR assignments of the thiopeptide antibiotic nosiheptide. AB - The 1H and 13C NMR spectra of nosiheptide have been assigned by use of 2D NMR techniques on unlabeled samples and biosynthetically multiple-labeled samples from stable isotope feeding experiments. PMID- 2584150 TI - C(3)-cyclopropyl cephems and carbacephems. AB - A series of C(3)-cyclopropyl cephems and carbacephems has been prepared by palladium catalyzed addition of diazomethane to the corresponding C(3)-vinyl derivatives. The phenylglycyl cyclopropyl cephem derivatives exhibit better Gram positive activity than cephalexin or cefaclor, while the aminothiazole oxime cyclopropyl cephem derivatives were not as active as the corresponding C(3)-vinyl cephems. PMID- 2584151 TI - Structure-activity relationship studies on 4''-O-acyltylosin derivatives: significance of their 23-O-mycinosyl and 4''-O-acyl moieties in antimicrobial activity against macrolide-resistant microbes. AB - Essential roles for both the 23-O-mycinosyl and 4''-O-acyl moieties of 4''-O acyltylosin derivatives in the expression of antimicrobial activity against multiple macrolide-resistant strains of Staphylococci and mycoplasmas were demonstrated by in vitro comparison of the MICs of erythromycin, josamycin, tylosin and its 3- and 4''-O-acyl derivatives, demycinosyltylosin (DMT) and its 3 and 4''-O-acyl derivatives and 23-modified 3-O-acetyl-4''-O-isovaleryl-DMT derivatives. PMID- 2584152 TI - Microbial conversion of anthracyclinones to carminomycins by a blocked mutant of Actinomadura roseoviolacea. AB - New anthracycline antibiotics, 1-hydroxy-11-deoxycarminomycin II and 11 deoxycarminomycin II were produced by a blocked mutant MuW1 of Actinomadura roseoviolacea from epsilon-pyrromycinone and aklavinone, respectively. We found that the enzyme catalyzing hydroxylation at the C-11 position was not lost but was down regulated in the strain MuW1. PMID- 2584153 TI - Potentiation of cytotoxicity and antitumor activity of adenosine analogs by the adenosine deaminase inhibitor adecypenol. PMID- 2584154 TI - Transduction of plasmid DNA in macrolide producing streptomycetes. PMID- 2584155 TI - Tubulin and microtubules in cochlear hair cells: comparative immunocytochemistry and ultrastructure. AB - The distribution of tubulin has been investigated in surface preparations of the guinea pig organ of Corti using indirect immunofluorescence microscopy. Two different monoclonal antibodies to tubulin produce similar distinct patterns of labelling in hair cells. Labelling is greater in inner hair cells than outer hair cells. It occurs in rings around the cell apex, and in a meshwork below and channels through, the cuticular plate. In outer hair cells from the apical region of the cochlea, labelling occurs around the location of a basalward protrusion of the cuticular plate. These patterns correlate with the location of microtubules observed using transmission electron microscopy. A large patch of labelling occurs on the strial side of the cell corresponding to the largest channel through the cuticular plate and the kinociliary basal body. Strands of labelling are seen running parallel to the long axis of the cell between the subcuticular and synaptic region. Many more of these strands are seen in the inner hair cell than the outer hair cell and may correspond to tracks of microtubules transporting neurotransmitter vesicles or other organelles. In outer hair cells, intense labelling and many microtubules are seen in the subnuclear region. The possible roles of the different microtubule arrangements are discussed. PMID- 2584156 TI - Selective damage to cochlear efferents by the choline neurotoxin ethylcholine mustard aziridinium ion (AF64A) in the chinchilla. AB - The cholinotoxin ethylcholine mustard aziridinium ion (AF64A) was diluted in artificial perilymph to concentrations ranging from 10-100 microM, injected unilaterally into the bulla of chinchillas, and allowed to passively diffuse across the round window membrane. Following 21-day survival, the animals were sacrificed and ears removed and embedded in epoxy for histological evaluation under both light and transmission electron microscopy. At 10 microM concentration, selective degeneration of efferent fibers was observed in the efferent terminals on outer hair cells (OHC), tunnel radial fibers, tunnel spiral bundle, and the inner spiral bundle. Serial sections of the middle turn of an animal at 10 microM concentrations showed normal efferent terminals on approximately 50% of OHCs. At the higher concentrations non-specific damage was seen in OHCs, afferents, and some supporting cells. These data suggest that low doses AF64A produces selective damage to cochlear efferent terminals and fibers in the chinchilla. PMID- 2584157 TI - Spontaneous rates, thresholds and tuning of auditory-nerve fibers in the gerbil: comparisons to cat data. AB - Characteristics of 245 auditory nerve fibers in eleven Mongolian gerbils are described in terms of spontaneous rates, thresholds, and tuning curves. The animals were reared in a low-noise environment and had similar hearing thresholds across frequency. Tuning curves were obtained with an algorithm developed to characterize the tuning of auditory fibers in cat, thereby allowing direct comparisons to published data from cat. The results demonstrate that basic similarities exist between gerbil and cat data, although some minor differences are also apparent. Tuning curve bandwidths, as measured 10 and 40 dB above the thresholds at the characteristic frequency (CF), follow trends found in cat data. Like cat, auditory nerve fibers in the gerbil have a range of spontaneous rates. In individual gerbils, fibers associated with low spontaneous rates have higher thresholds than do fibers of similar CF with high rates. Five of the eleven gerbils showed profiles of spontaneous rate across frequency reminiscent of those obtained from quiet-raised young cats. The profiles of the remaining gerbils tended to be compressed to a smaller range of spontaneous rates for characteristic frequencies above about five kHz, much like older cats with unknown noise histories. The cause of the spontaneous compression is not obvious. The correspondence between cat and gerbil with regard to spontaneous rate and CF threshold implies the presence of fundamental mechanisms that are common to mammalian auditory systems. PMID- 2584158 TI - Comodulation masking release for three types of modulator as a function of modulation rate. AB - To investigate the dependence of 'Comodulation Masking Release' (CMR) on the type and frequency of modulator, thresholds were measured for a 4-kHz tone masked by modulated and unmodulated noises. The maskers were a 400-Hz wide band of noise centered on 4 kHz (NOCUE), the same noise with a 2700-Hz lowpass noise added (LPCUE), and a wideband noise with a passband between 3 and 6 kHz (WBCUE). In each condition three types of modulator were used: a square wave, a sinewave, and a lowpass noise. Several frequencies of each type of modulator were used, allowing measurement of the interaction between envelope frequency (fe) and modulator type. Thresholds were lower in the presence than in the absence of modulation for all modulator types, except when fe was high (e.g. 100 Hz). The 'Modulated-Unmodulated Difference' (MUD) decreased monotonically with increasing fe in all conditions. For any given fe, MUDs generally were greater for square wave and lowpass-noise modulation than for sinusoidal modulation. As significant MUDs were sometimes obtained even in the NOCUE condition, the MUD was not an accurate measure of CMR. Therefore, CMR was defined as the difference between the MUD obtained in the NOCUE condition and that obtained in each cue condition, for each combination of fe and modulator type. Measured this way, the CMR for our 4 kHz signals did not vary systemically with fc over the range studied. When a CMR was obtained it was smaller for sinusoidal modulation than for either square-wave or lowpass-noise modulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584159 TI - Lower boundaries of two-tone suppression regions in the guinea pig. AB - Lower boundaries of two-tone suppression regions were determined in single fibres of the guinea pig with a tracking algorithm as described by Schmiedt (1982). For a suppressee at CF having a level of 20 dB above the threshold of the tip, suppression at the high-frequency (hf) side of the FTC could almost always be found. With the method used, the percentage of fibres in which suppression could be found at the low-frequency (lf) side of the FTC decreased with decreasing CF. Moreover, the occurrence of lf-suppression decreased for lower suppressee levels for fibres with CF approximately 2-5 kHz. For each fibre the minimum level difference between lf-suppression boundary and tip threshold was larger than 20 dB, for the whole group of fibres the difference was 34 dB on average. The hf suppression regions sometimes reached below the tip for fibres with CFs in the 4 kHz region. The frequency at the lowest level of the hf-suppression boundary, best suppression frequency or BSF, is related to the CF as: BSF = 0.55 + 1.13 CF. When the suppressee level increased, the lower boundary at the hf side shifted upwards with a rate greater than 1 dB/dB. On the whole the two-tone suppression data in the guinea pig agree with those found in other rodents. PMID- 2584160 TI - CGRP-like immunoreactivity in the guinea pig organ of Corti: a light and electron microscopy study. AB - We examined calcitonin-gene related peptide (CGRP)-like immunoreactivity in the guinea pig organ of Corti at both the light and electron microscope level using immunofluorescence and immunoperoxidase techniques. We observed strong CGRP-like immunoreactivity in the inner spiral bundle and tunnel spiral bundle in all turns at both the light and electron microscope level. CGRP immunostaining was localized exclusively in vesiculated efferent fibers. The majority of these fibers in the inner spiral bundle were immunoreactive. We observed immunostained synaptic junctions between two efferent fibers and between efferent varicosities and afferent dendrites. In the region of the outer hair cells (OHC), we found CGRP-like immunoreactivity in the efferent endings at the base of OHCs and at the level of the OHC nucleus. At the base of OHCs, CGRP reactive endings in the first, second and more rarely the third row. CGRP immunoreactivity was localized in large dense core vesicles. In summary, our data demonstrate that the neuropeptide, CGRP, was found in both the lateral and medial efferent systems. Secondly, the immunoreactivity was localized in large dense core vesicles. PMID- 2584162 TI - Loving Hands get a slap in New Zealand. PMID- 2584161 TI - The form and distribution of GABAergic synapses on the principal cell types of the ventral cochlear nucleus of the cat. AB - The distribution of GABAergic endings was examined histochemically in the ventral cochlear nucleus (VCN) of the cat using an antibody to glutamate decarboxylase (GAD), the synthetic enzyme for GABA. Immunoreactive (GAD+) endings appeared in all subdivisions of the cat VCN. Each of the principal cell types had a characteristic labeling pattern, based on the size, concentration, and distribution of GAD+ endings on its soma. Spherical bushy cell somata were typically contacted by many small (less than 1.5 microns in diameter) and medium sized (1.5-2 microns in diameter) endings, many of which aggregated into tight clusters. Globular bushy cells had a similar pattern, but the clusters of GAD+ endings were less tightly packed. Reactive endings on stellate cells were more evenly distributed. GAD+ endings on octopus cells were larger (up to 2.5 microns in diameter) than those on the bushy cells and tended to aggregate into small clusters or rows on the somata and dendrites. Reactive endings contained small pleomorphic vesicles and formed symmetrical synaptic contacts on each of the cell types examined. The patterns formed by GAD+ endings on each type of neuron resemble those of certain types of non-cochlear axons previously described with the Golgi methods as projecting from the dorsal cochlear nucleus and the trapezoid body. PMID- 2584163 TI - Stress, satisfaction, and coping: a study of women clerical workers. AB - Increasing numbers of women in the work force have prompted researchers to study the health impact of their work satisfactions and stressors. In this study, we examined the quality of the work role as perceived by women who hold clerical jobs. Qualitative data were collected through structured interviews with 87 female clerical workers employed in four organizational settings. All were mothers with one or more children living at home. Work satisfaction, work stressors, coping strategies, and resources were discussed in the interviews. Categories were developed for each of these areas. The Ethnograph computer program was used after content analysis to code and retrieve the responses for each category. PMID- 2584165 TI - Promiscuity that (which?) can frustrate your efforts at communication. PMID- 2584164 TI - Women's responses to sexual abuse in intimate relationships. AB - One hundred ninety-three women having serious problems in an intimate relationship with a man were recruited by newspaper advertisement to participate in this study. Of the 97 battered women, 44.3% also were being sexually abused. Sexual abuse was inversely correlated with body image and self-esteem scores and positively related to danger of homicide, even when severity and frequency of violence were controlled for. Assessment and interventions for sexual abuse are necessary in all women's health settings, especially if a woman is battered. PMID- 2584166 TI - Occurrence of Erysipelothrix rhusiopathiae on pork and in pig slurry, and the distribution of specific antibodies in abattoir workers. AB - Strains of Erysipelothrix rhusiopathiae isolated at 19 pig farms serving a certain abattoir, and on pork and in workers of this abattoir were studied. Mouse pathogenic E. rhusiopathiae was found in pig slurry from two farms (11%). The strains belonged to serotypes 7 and 16 (both from the same farm) or were untypable. In pig slurry from the abattoir lairage only serotype 2 strains were found and all were pathogenic to mice. Mouse-pathogenic E. rhusiopathiae strains of serotype 2 were also recovered from 25 pork lions (25%). A mouse-pathogenic E. rhusiopathiae (serotype 2) strain was isolated from one of the 16 hand infections of slaughterhouse workers. The E. rhusiopathiae strains were phenotypically grouped by the API 50 CH system. Variations were demonstrated for the different serotypes. In 20 of 138 workers antibodies against E. rhusiopathiae were found; 14 had increased levels of IgG antibodies, seven had increased levels of IgM antibodies and one had an increased level of both. PMID- 2584167 TI - Identification of psychrotrophic pseudomonads from goats' milk by computer assisted analysis of carbon source assimilation data. AB - The results of carbon source assimilation tests on a group of psychrotrophic pseudomonas were compared with published data for established Pseudomonas taxa, using computer-assisted numerical taxonomic analysis and a modified diagnostic computer program. Several phenons were not grouped at the biovar level by numerical taxonomic analysis. Identification of strains by the diagnostic program revealed heterogeneity among those in the unassigned phenons, and supported a continuum concept among the fluorescent pseudomonads. PMID- 2584168 TI - Rapid detection of staphylococcal enterotoxins in foods with a modification of the reversed passive latex agglutination assay. AB - A modification of the reversed passive latex agglutination kit assay for detection of staphylococcal enterotoxins by centrifugation of microtitration plates reduces the incubation time of the assay from 20-24 h to 4 h. Enterotoxins can therefore be detected in foods within the working day. PMID- 2584169 TI - The faecal flora of the giant panda (Ailuropoda melanoleuca). AB - The faecal floras of two adult (male and female) and one infant (male) giant panda kept at the Ueno Zoo, Tokyo, Japan were examined and shown to be quite different from those of other animals. The predominant bacteria in the adults were Streptococcus (including Enterococcus) and Enterobacteriaceae, while obligate anaerobes had minor populations. Fastidious anaerobes were not detected. The predominant bacteria in the suckling infant were Lactobacillus and Streptococcus, followed by Bifidobacterium. After the infant began to eat bamboo leaves the number of Lactobacillus decreased and Bifidobacterium became undetectable, whereas Enterobacteriaceae became one of the most predominant flora. The most dominant streptococcus isolated from the female panda was identified as Streptococcus bovis, but those from the male adult and the weaned infant were not identified as any known species. PMID- 2584171 TI - A note on the isolation and propagation of lytic phages from Streptococcus uberis and their potential for strain typing. AB - Thirty-eight of 98 strains of Streptococcus uberis were shown to be carrying lysogenic phage. Although propagating strains were rare, host modification by field strains sensitive to phage was used to increase the lytic spectra. When 120 nationally-collected strains were challenged with 25 phages, selected on the basis of differing lytic spectra and propagating strains, 30% were susceptible to at least one phage, increasing to 42% when 480 strains from a single farm were considered. A typing system based on susceptibility to lytic phage was considered feasible. PMID- 2584170 TI - The preservation of micro-organisms in biological specimens stored at-70 degrees C. AB - The preservation of micro-organisms that may be found on the skin was studied by storage in liquid media at--70 degrees C. In the first part of the study the performance of 12 varieties of suspending media was evaluated with pure cultures of 17 species of micro-organisms maintained in the laboratory. After storage for 1 year the best medium (Oxoid Nutrient Broth with 15% glycerol) showed a mean survival for all organisms studied of 83.8%, with no significant differences between organisms. Even the worst medium (distilled water) permitted greater than 40% survival at 1 year. No changes in the characteristics of these micro organisms were detected after 6 months storage in glycerol broth. In the second part of the study nose swabs were suspended in one representative medium (Bacto Nutrient Broth containing 7% glycerol). The mean percentage survival of staphylococci in these suspensions after 1 year's storage at - 70 degrees C was 75.4%. These results indicate that coagulase-negative coagulase-negative staphylococci in samples of skin flora may be stored under these conditions for long periods, greatly reducing the work-load in epidemiological studies of infection. PMID- 2584172 TI - A procedure for urease and protein extraction from staphylococci. AB - Staphylococcal cell protein and urease can be solubilized after growth in Todd Hewitt broth supplemented with 0.5% yeast extract by extraction for 18-24 h in phosphate buffer, pH 7.0. In general 20% (but up to 100%) of the urease present in the original cells could be solubilized. Less protein was solubilized. Species examined included coagulase-negative staphylococci, Staphylococcus intermedius and Staph. aureus. Extracts of Staph. epidermidis prepared by this procedure gave electrophoretic urease and protein patterns similar to those prepared by sonication. The procedure was simple and minimized handling of the cells. PMID- 2584173 TI - Numerical analysis of electrophoretic protein patterns of Providencia rettgeri strains from human faeces, urine and other specimens. AB - Thirty-one strains of Providencia rettgeri (mainly from humans) were characterized by one-dimensional SDS-PAGE of cellular proteins. The strains came from various countries and comprised 14 from urine, eight from faeces, two from bile (plus one from the liver of a sheep), two from sputum, one from an insect pupa and three the sources of which were unknown. Also included, for reference purposes, were the type strains of the four other Providencia species. The protein patterns, which contained 45-50 discrete bands, were highly reproducible and were used as the basis for two numerical analyses. In the first, which included all the protein bands, the 31 Prov. rettgeri strains formed 13 clusters at the 84% S level. In the second analysis, in which the principal protein bands (in the 33.3-41.3 kD range) were excluded, 29 of the 31 Prov. rettgeri strains formed a single cluster at the 81% S level, whilst the four Providencia reference strains remained unclustered. We conclude that high resolution PAGE combined with computerized analysis of protein patterns provides the basis for typing clinical strains of Prov. rettgeri. Reference strains of each of the 13 PAGE types identified are available from NCTC for inclusion in future studies. PMID- 2584174 TI - The inotropic consequences of cooling: studies in the isolated rat heart. AB - To investigate the controversial effects of hypothermia on cardiac contractile performance, we have carried out ventricular volume-loading experiments in 23 perfused, paced (2 Hz), isolated rat hearts, contracting isovolumically at various temperatures. A water-filled, unstressed latex balloon was inserted into the left ventricle and its volume was controlled with a microsyringe. Left ventricular pressure (LVP), its first derivative (dP/dt) and coronary flow were recorded. One group of hearts (n = 7) were perfused at 37 degrees C over 2 h. Another group of hearts (n = 16) were cooled in a stepwise manner from 37 degrees C to 21 degrees C, with 10-min perfusion at each of seven different temperatures, and then rewarmed to 37 degrees C. Emax, an index of contractility, calculated as the slope of the regression line of the end-systolic pressure-volume relationship, was found to increase as temperature fell (3.9, 4.6, 4.9, 5.5, 5.5, 6.2, and 6.3 cm H2O/microliters at 37 degrees, 34 degrees, 31 degrees, 29 degrees, 27 degrees, 24 degrees and 21 degrees C, respectively) while it remained constant over the 2-h perfusion in the normothermic perfusion group. By contrast, peak positive dP/dt/peak-developed pressure (+dP/dt/DP) progressively decreased during cooling without any change in the normothermic perfusion group. The results indicate that hypothermia can be designated as a positive inotropic intervention in terms of force-generation (Emax) but as a negative inotropic intervention in terms of shortening velocity of contractile element in Hill's model (+dP/dt/DP). PMID- 2584176 TI - Diastolic compliance of the left atrium in man: a determinant of preload of the left ventricle. AB - During the ventricular slow-filling period, both the left atrium and left ventricle fill passively, and their respective internal pressures equalize, becoming evenly elevated. If the diastolic chamber compliance of the left atrium is smaller than that of the left ventricle, we expect the inflowing blood to be distributed more to the left ventricle than to the left atrium during this period. We examined the magnitude of the diastolic compliance of the left atrium and the left ventricle at the end of the slow-filling period. We studied 10 patients, mostly with a mild degree of coronary artery disease, in whom hemodynamic variables were almost within normal limits. To estimate the compliance of the left atrium, we recorded the left atrial pressure directly (by the Brockenbrough technique) and determined the left atrial volume by biplane cineatriography. We determined the diastolic compliance of the left atrium from the pressure-volume relations between the nadir of the x trough and the peak of the v wave by fitting them to an exponential equation. P = b.eaV (P = pressure, V = volume, a, b = constants). The diastolic compliance of the left ventricle was determined from the pressure-volume relations during the ventricular slow-filling period. The compliances of the left atrium and the left ventricle at the pressure at the end of the ventricular slow-filling period were 1.60 +/- 0.41 (mean +/- SD) ml.mmHg-1.m-2 and 4.22 +/- 1.12, respectively. The ratio of compliance of the left ventricle to that of the left atrium was 2.60 +/- 0.71.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584175 TI - Effect of ouabain on the relation between left ventricular oxygen consumption and systolic pressure-volume area (PVA) in dog heart. AB - We studied the effect of ouabain (digitalis) on the relation between left ventricular (LV) O2 consumption (VO2) and pressure-volume (P-V) area (PVA) in 7 excised cross-circulated canine heart preparations. PVA is a measure of the total mechanical energy generated by LV contraction and was obtained as the specific area in the P-V diagram circumscribed by the end-systolic P-V line, end-diastolic P-V curve, and the systolic P-V trajectory. Ouabain (0.11 mg, intracoronary arterially) increased Emax (LV contractility index) by 58 +/- 44% (mean +/- SD) from 7.8 +/- 3.4 to 12.0 +/- 4.8 mmHg/(ml/100 g LV). PVA correlated linearly with LV VO2 per beat in either the control (r greater than 0.97) or the ouabain run (r greater than 0.96) in individual hearts. Ouabain increased the VO2-axis intercept of the regression line of VO2 on PVA from 0.029 +/- 0.004 in the control run to 0.036 +/- 0.009 ml O2/beat/100 g LV without significantly changing the slope [(1.53 +/- 0.24).10(-5) ml O2/(mmHg/ml)] of the regression line. This slope is equivalent to the contractile efficiency value of 44 +/- 6% from the excess VO2 above unloaded VO2 to PVA. The parallel elevation of the VO2-PVA relation with ouabain was similar to the results produced by epinephrine and Ca2+ in our previous studies. Ouabain, like epinephrine and Ca2+, did not change the contractile efficiency from the PVA-dependent fraction of VO2 to PVA. PMID- 2584177 TI - Strength, elasticity and viscoelastic properties of cerebral aneurysms. AB - Tissue strength and stiffness of cerebral aneurysm walls obtained intraoperatively or at autopsy were evaluated by uniaxial strain/stress measurements. For comparison, corresponding measurements were also made on autopsy specimens of intracranial arteries. The maximum stress that the aneurysm tissue could tolerate, the yield stress, was found to be slightly lower than in arteries, which is likely due to the content of immature forms of collagen. The material stiffness, as determined by division of the yield stress by the corresponding strain, was also smaller in aneurysms than in arteries. The stress resistance of aneurysms and arterial tissue decreased over a period of several hours. The relaxation curves were found to be identical in aneurysms and arteries. The stress tolerated by aneurysm walls was found to be in the range of the stress that is imposed in vivo by the blood pressure. Arteries resisted stresses corresponding to pressures 5-10 times higher than physiological values. It is suggested that the balance of tissue strength and the stress imposed by the blood pressure is causally related to aneurysm growth. PMID- 2584178 TI - Long-term prognosis of Kawasaki disease patients with coronary artery obstruction. AB - The prognosis of coronary artery obstruction was studied in patients with Kawasaki disease. Between May 1973 and December 1987, coronary artery obstruction was diagnosed by coronary angiography in 30 patients (21 males, 9 females), of whom, only 8 (26.7%) had clinical symptoms. One patient died after 9 years of illness. Two complained of frequent chest pain, which disappeared after bypass surgery in one case and spontaneously in the other. Five had symptomatic myocardial infarction. Myocardial ischemia was diagnosed in 31.8% by treadmill stress testing, but was well demonstrated in 85.7% by thallium-201 myocardial tomography. Frequent ventricular premature beats, Wenckebach-type atrioventricular block, and ST-segment depression accompanied by chest pain were recognized by 24-h Holter monitoring. In the past, the methods used to determine the prognosis of Kawasaki disease patients with coronary artery obstruction were not adequate. However, the examinations used in this study revealed an improved ability to determine the prognosis in this disease. Myocardial tomography, in particular, provided a more accurate evaluation of myocardial damage. Ventricular arrhythmias seem to be a serious problem in these patients. Therefore, careful observation using these tests, especially myocardial tomography and Holter monitoring, should be done even if the patients are free of symptoms. PMID- 2584179 TI - A case of aortic intimal sarcoma manifested with acutely occurring hypertension and aortic occlusion. AB - Primary tumor of the aorta is extremely rare. An instance of aortic intimal sarcoma, namely fibromyxosarcoma, which extended from the beginning of the descending aorta to 7 cm above the abdominal bifurcation, with clinical evidence of acutely occurring hypertension, arterial embolism of the lower extremities, renal infarction, and aortic occlusion in a 50-year-old male is reported. The tumor was limited to the intima and composed of spindle-shaped tumor cells with abundant myxoid extracellular matrices. The tumor cells were negative for Factor VIII, Desmin, or Myoglobin, but were positive for Vimentin or Factor XIIIa in immunoperoxidase studies. An electron microscopic examination revealed a large amount of rough endoplasmic reticulum in the cytoplasm. Parenchymal metastases were observed in both the lungs and thoracic vertebrae. A review of literature on the clinical and pathological aspects of the tumor was made. PMID- 2584180 TI - Reperfusion through balloon catheter to minimize myocardial infarction during the interval between failed percutaneous transluminal coronary angioplasty and emergency coronary artery bypass grafting. AB - A 65-year-old man was admitted with chest pain. A diagnosis of spastic angina was made because of symptoms of recurrent anginal attacks associated with ST-segment elevations in the electrocardiogram. A selective coronary arteriogram revealed a 90% diameter narrowing of the proximal left anterior descending coronary artery (LAD). No angiographically visible collaterals from the right coronary artery to the LAD were observed. The ventriculogram showed normal contraction of the left ventricle with an ejection fraction of 65%. Percutaneous transluminal coronary angioplasty (PTCA) failed resulting in total occlusion of the stenosis. Repeat PTCA at a higher pressure and of longer duration failed to redilate the artery. Reperfusion with the blood from the femoral artery through the balloon catheter, which was used for the PTCA, was carried out until coronary artery bypass grafting (CABG). Blood flow rate of perfusion was approximately 25 ml/min. Reperfusion through the balloon catheter reduced chest pain and ST-segment elevations in the electrocardiogram. The patient tolerated the operative procedure well and his post-operative course was uncomplicated. The interval between the acute occlusion and revascularization by CABG was approximately 4 1/4 h. The ventriculogram taken 56 days after the CABG demonstrated normal contraction of the anterior wall of the left ventricle with an ejection fraction of 63%. Abnormal Q waves did not appear in precordial leads of the electrocardiogram after the surgery. The thallium scintigram showed no perfusion defects. In conclusion, this case suggested that autologous blood reperfusion through balloon catheter would be worth attempting in some cases for minimization of myocardial infarction during the interval between failed PTCA and emergency CABG. PMID- 2584181 TI - Alterations in the phosphorylation and activity of DNA polymerase alpha correlate with the change in replicative DNA synthesis as quiescent cells re-enter the cell cycle. AB - The regulation of DNA polymerase alpha was examined in quiescent, human fibroblast cells stimulated to re-enter the cell cycle by subculturing in fresh serum-containing medium. The level of DNA polymerase alpha activity was measured in cell lysates and after specific immunoprecipitation. DNA polymerase alpha activity increased approximately 10-fold during the period of measurement. The activity increase was coincident with an approximately 60-fold increase in thymidine incorporation in the whole cells representing the first S phase. The large increase in polymerase alpha activity was not predominantly the result of synthesis of new polymerase, since the abundance of the enzyme changed less than 2-fold over the measured period. The quantity of [32P]phosphate incorporated into two subunits (180 and 68 kilodaltons) of DNA polymerase alpha increased approximately 10-fold in parallel with the increase in polymerase activity. The specific activity of the cellular ATP pool remained nearly constant over the period of measurement, indicating that the increase in labeling reflects a true increase in incorporation of phosphate. Results from other laboratories indicate that phosphorylation of DNA polymerase alpha increases its catalytic activity. Our results then suggest that the activity increase observed in DNA polymerase alpha when quiescent, human fibroblasts are stimulated to proliferate is largely caused by a phosphorylation-dependent regulatory process. PMID- 2584182 TI - Structure of the gene for human von Willebrand factor. AB - von Willebrand factor is a large multimeric plasma protein composed of identical subunits which contain four types of repeated domains. von Willebrand factor is essential for normal hemostasis, and deficiency of von Willebrand factor is the most common inherited bleeding disorder of man. Four human genomic DNA cosmid libraries and one bacteriophage lambda library were screened with von Willebrand factor cDNA probes. Twenty positive overlapping clones were characterized that span the entire von Willebrand factor gene. A high-resolution restriction map was constructed for approximately 75% of the locus and a total of approximately 33.8 kilobases was sequenced on both strands including all intron-exon boundaries. The gene is approximately 178 kilobases in length and contains 52 exons. The exons vary from 40 to 1379 base pairs in length, and the introns vary from 97 base pairs to approximately 19.9 kilobases in length. The signal peptide and propeptide (von Willebrand antigen II) of von Willebrand factor are encoded by 17 exons in approximately 80 kilobases of DNA while the mature subunit of von Willebrand factor and 3' noncoding region are encoded by 35 exons in the remaining approximately 100 kilobases of the gene. A number of repetitive sequences were identified including 14 Alu repeats and a approximately 670-base pair TCTA simple repeat in intron 40 that is polymorphic. Regions of the gene that encode homologous domains have similar structures, supporting a model for their origin by gene segment duplication. PMID- 2584183 TI - Primary structure of the maize NADP-dependent malic enzyme. AB - Chloroplast-localized NADP-dependent malic enzyme (EC 1.1.1.40) (NADP-ME) provides a key activity for the carbon 4 fixation pathway. In maize, nuclear encoded NADP-ME is synthesized in the cytoplasm as a precursor with a transit peptide that is removed upon transport into the chloroplast stroma. We present here the complete nucleotide sequence for a 2184-base pair full-length maize NADP ME cDNA. The predicted precursor protein is 636 amino acids long with a Mr of 69,800. There is a strong codon bias found in the amino-terminal portion of NADP ME that is present in genes for the other enzymes of the C-4 photosynthetic pathway. The NADP-ME transit peptide has general features common to other known chloroplast stroma transit peptides. Comparison of mature maize NADP-ME to the amino acid sequences of known malic enzymes shows two conserved dinucleotide binding sites. There is a third highly conserved region of unknown function. On the basis of amino acid sequence similarity, the maize chloroplastic enzyme is more closely related to eukaryotic cytosolic isoforms of malic enzyme than to prokaryotic isoforms. We discuss the functional and evolutionary relationship between the chloroplastic and cytosolic forms of NADP-ME. PMID- 2584184 TI - Thiophosphorylation causes Ca2+-independent norepinephrine secretion from permeabilized PC12 cells. AB - Adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S) was used to examine the role of phosphorylation in the regulation of norepinephrine secretion by digitonin permeabilized PC12 cells. While most kinases will use ATP gamma S to thiophosphorylate proteins, thiophosphorylated proteins are relatively resistant to dethiophosphorylation by protein phosphatases. Norepinephrine secretion by permeabilized PC12 cells was ATP- and Ca2+-dependent but resistant to calmodulin antagonists. Half-maximum secretion was obtained in 0.75 microM Ca2+. Permeabilized PC12 cells were incubated with ATP gamma S in the absence of Ca2+, the ATP gamma S was removed, and norepinephrine secretion was determined. Preincubation with ATP gamma S increased the amount of norepinephrine secreted in the absence of Ca2+, but it had no effect on the amount released in the presence of Ca2+. After a 15-min preincubation in 1 mM ATP gamma S, there was almost as much secretion in the absence of Ca2+ as in its presence. Inclusion of ATP in the preincubation inhibited the effect of ATP gamma S. Ca2+ stimulated the rate of modification by ATP gamma S as brief preincubations with ATP gamma S in the presence of Ca2+ resulted in higher levels of Ca2+-independent secretion than did preincubations with ATP gamma S in the absence of Ca2+. Similarly, brief preincubations of permeabilized cells with ATP in the presence of Ca2+ resulted in elevated levels of Ca2+-independent secretion. Secretion of norepinephrine from ATP gamma S-treated cells was ATP-dependent. These results suggest that norepinephrine secretion by PC12 cells is regulated by a Ca2+-dependent phosphorylation. Once this phosphorylation has occurred, secretion is still ATP dependent, but it no longer requires Ca2+. PMID- 2584185 TI - The transition of RNA polymerase II from initiation to elongation is associated with phosphorylation of the carboxyl-terminal domain of subunit IIa. AB - Mammalian cells contain two forms of RNA polymerase II, designated IIO and IIA, that differ in the extent of phosphorylation within the C-terminal domain of their largest subunit. Phosphorylation of this domain, which results in the conversion of RNA polymerase IIA to IIO, may play an important role in the transition from the initiation to the elongation phase of transcription. A third form of the enzyme, RNA polymerase IIB, is found in vitro and lacks the repetitive C-terminal domain. Purified calf thymus RNA polymerase IIA was labeled selectively with casein kinase II in the presence of [gamma-32P]ATP and used as substrate for the identification and partial purification of factors that catalyze the conversion of RNA polymerase IIA to IIO. HeLa cell S-100 transcription extracts contain such an activity that cofractionates with factors essential for promoter-dependent transcription through heparin-Sepharose, DEAE 5PW, and DE52 chromatography. The activity is dependent on either ATP, GTP, or dATP, requires a hydrolyzable beta,gamma-phosphoanhydride bond, and cannot utilize pyrimidine nucleoside triphosphates. This observation supports the idea that the conversion activity is a protein kinase. Transcription of the major late promoter of adenovirus-2 was carried out in the presence of a reconstituted transcription extract containing purified RNA polymerases IIO, IIA, or IIB, and the nature of the elongating enzyme was determined by photoaffinity labeling. When the reaction was initiated with RNA polymerase IIO or IIB, nascent transcripts were found cross-linked to subunit IIo or IIb, respectively. However, when the reaction was initiated with RNA polymerase IIA, nascent transcripts were cross-linked to subunit IIo. Consequently, phosphorylation of the C-terminal domain of subunit IIa must have occurred prior to elongation. The copurification of RNA polymerase IIA to IIO conversion activity with factors essential for promoter-dependent transcription and the observation that RNA polymerase II containing an unphosphorylated C-terminal domain is phosphorylated prior to elongation suggest that protein kinases that phosphorylate the C-terminal domain of subunit IIa may play an essential role in transcription. PMID- 2584186 TI - Macrophage oxidation of L-arginine to nitric oxide, nitrite, and nitrate. Tetrahydrobiopterin is required as a cofactor. AB - A new metabolic pathway characterized recently that is expressed in activated macrophages involves the formation of nitric oxide ('N = O) as an intermediate. The 'N = O formed decomposes to nitrite (NO2-) and nitrate (NO3-). The substrate for the reaction is the amino acid arginine which is oxidized at the guanido nitrogen to yield citrulline as the other product of the reaction. The studies reported here show that the activity for this unusual oxidation reaction which is contained in the 100,000 x g supernatant was lost after desalting on a Sephadex G 25 column. A small molecule cofactor was found to be required for the restoration of activity. The addition of (6R)-tetrahydrobiopterin (BH4) and NADPH led to complete recovery of activity in this desalted protein. Analysis of macrophage cell extracts, using high performance liquid chromatography with electrochemical detection, showed that BH4 was present at 17 pmol/10(6) cells or 2.1 microM in macrophage supernatant. Only the (6R)-isomer was present. With the addition of BH4 and NADPH, there was loss of arginine that was equal to the NO2-, NO3-, and citrulline formed. With substoichiometric levels of NADPH relative to BH4, the loss of arginine was greater than the formation of the end products of the reaction. A scheme for the reaction pathway consistent with the results involves N-hydroxylation of arginine as the initial step. The participation of BH4 in this type of oxidative chemistry is consistent with previous characterizations of this co-factor. PMID- 2584187 TI - A histidine residue at the active site of avian liver phosphoenolpyruvate carboxykinase. AB - The histidine-selective reagents diethylpyrocarbonate (DEPC) and dimethylpyrocarbonate were used to study active site residues of phosphoenolpyruvate carboxykinase. Both reagents show pseudo first-order inhibition of enzyme activity at 22 +/- 1 degree C with calculated second-order rate constants of 2.8 and 4.6 M-1 s-1, respectively. The inhibition appears partially reversible. Substrates affect the rate of inhibition: KHCO3 enhances the rate, Mn2+ has little effect, and phosphoenolpyruvate decreases the rate. The best protection is obtained by IDP or IDP and Mn2+. The kinetic studies show that modification of histidine is specific and leads to loss of enzymatic activity. Two histidines per enzyme are modified by DEPC, as measured by an absorption change at 240 nm, in the absence of substrate, leading to loss in activity. One histidine per molecule is modified in the presence of KHCO3, giving inactivation. Cysteine and lysine residues are not affected. A study of the inhibition rate constant as a function of pH gives a pKa of 6.7. Enzyme modified by DEPC in the absence of substrate (1% remaining activity) shows no binding of ITP or of phosphoenolpyruvate to the enzyme.Mn2+ complex as studied by proton relaxation rates. When enzyme is modified in the presence of KHCO3 (44% remaining activity), ITP and KHCO3 bind to the enzyme.Mn2+ complex similarly to the binding to native enzyme. Phosphoenolpyruvate binding to modified enzyme.Mn results in an enhancement of proton relaxation rates rather than the decrease observed with native enzyme.Mn. The CD spectra of histidine-modified enzyme show a decrease in alpha-helical and random structure with an increase in anti-parallel beta-sheet structure compared to native enzyme. These results show that avian phosphoenolpyruvate carboxykinase has 2 histidine residues which are reactive with DEPC and dimethylpyrocarbonate, and one of the 15 histidine residues in the protein is at or near the phosphoenolpyruvate binding site and is involved in catalysis. PMID- 2584188 TI - Interaction of thiocyanate with horseradish peroxidase. 1H and 15N nuclear magnetic resonance studies. AB - Interaction of thiocyanate with horseradish peroxidase (HRP) was investigated by relaxation rate measurements (at 50.68 MHz) of the 15N resonance of thiocyanate nitrogen and by following the hyperfine shifted ring methyl proton resonances (at 500 MHz) of the heme group of SCN-.HRP solutions. At pH 4.0, the apparent dissociation constant (KD) for thiocyanate binding to HRP was deduced to be 158 mM from the relaxation rate measurements. Chemical shift changes of 1- and 8-ring methyl proton resonances in the presence of various amounts of thiocyanate at pH 4.0 yielded KD values of 166 and 136 mM, respectively. From the pH dependence of KD and the 15N resonance line width, it was observed that thiocyanate binds to HRP only under acidic conditions (pH less than 6). The binding was found to be facilitated by protonation of an acid group on the enzyme with pKa 4.0. The pH dependence of the 15N line width as well as the apparent dissociation constant were quantitatively analyzed on the basis of a reaction scheme in which thiocyanate in deprotonated ionic form binds to the enzyme in protonated acidic form. The KD for thiocyanate binding to HRP was also evaluated in the presence of an excess of exogenous substrates such as resorcinol, cyanide, and iodide ions. It was found that the presence of cyanide (which binds to heme iron at the sixth coordination position) and resorcinol did not have any effect on the binding of thiocyanate, indicating that the binding site of the thiocyanate ion is located away from the ferric center as well as from the aromatic donor binding site. The KD in the presence of iodide, however, showed that iodide competes with thiocyanate for binding at the same site. The distance of the bound thiocyanate ion from the ferric center was deduced from the 15N relaxation time measurements and was found to be a 6.8 A. From the distance as well as the change in the chemical shifts and line width of 1- and 8-methyl proton resonances, it is suggested that the binding site of thiocyanate may be located near heme, placed symmetrically with respect to 1- and 8-methyl groups of the heme of HRP. Similarity in the modes of binding of iodide and thiocyanate suggests that the oxidation of thiocyanate ion by H2O2 may also proceed via the two-electron transfer pathway under acidic conditions, as is the case for iodide. PMID- 2584189 TI - Calcium-induced shape change of calmodulin with mastoparan studied by solution X ray scattering. AB - Solution x-ray scattering using synchrotron radiation as an x-ray source was used to analyze the Ca2+-dependent shape change of pig brain calmodulin in detail. The radius of gyration of calmodulin at 10 mg/ml was increased by 0.9 A. The increase was nearly completed when 2.5 mol of Ca2+/mol of calmodulin was added, whereas the radius of gyration of calmodulin with mastoparan decreased by about 3 A with an increasing Ca2+ concentration up to 4 mol of Ca2+/mol of calmodulin. At a moderate angle of region, both scattering profiles from calmodulin with or without Ca2+ displayed clear humps at s = 0.03 A-1 which are characteristic of a dumbbell structure. However, in the presence of mastoparan, the hump in the scattering profile became obscure and later disappeared with the third and fourth Ca2+ binding to calmodulin. These findings are attributable to the Ca2+-induced shape change of calmodulin with mastoparan from a dumbbell structure to a non dumbbell structure in which the distance between the two lobes of calmodulin become closer by a bend in the central helix. PMID- 2584190 TI - Functionally distinct agonist and receptor-binding regions in human chorionic gonadotropin. Development of a tertiary structure model. AB - The histidine residues in human chorionic gonadotropin (hCG) were chemically modified using diethyl pyrocarbonate. Derivatives of hCG with an average of 0.5 3.5 histidines modified (maximum of 4 per hCG) had reduced receptor-binding and cell-stimulating activities. Acylation of hCG at progressively lower pH values (conditions in which 1 of the 2 absolutely conserved histidines alpha His-83 is not titratable, whereas alpha His-94 becomes increasingly protonated and resistant to modification) produced hCG derivatives with a greater retention of receptor-binding activity than cell-stimulating activity. The involvement of alpha His-94 as part of the receptor-binding region of the hormone and of alpha His-83 as a putative active site residue was inferred. Proteinaceous protease inhibitors were shown to neutralize the agonist activity of hCG and to reduce the binding of hCG to its receptor and also to specific antisera. It was presumed that an inhibitor-hormone complex was formed which was analogous to the complexing of inhibitor with the "substrate pocket" of a serine protease. The discovery of primary sequence analogies between hCG and the serine protease chymotrypsin enabled the prediction of hCG structure using the enzyme as a folding template. Solvent-exposed and buried core regions of the peptide chain were delineated using smoothed hydrophobicity profiles in combination with Chou Fasman secondary structure predictions. Hypervariable hydrophobicity indices between residues 38 and 80 of the human beta subunits reflected different folding arrangements which presumably conferred the individual receptor specificities. When mapped to the putative structure these receptor-determinant loops were adjacent to an area of the alpha subunit analogous to the substrate pocket of serine proteases. Disulfide bond assignments and intersubunit contact regions were identifiable. The proposed tertiary structure for hCG manifests the topographical epitopes defined using monoclonal antibodies and satisfies the currently available data on specific modification and its effects upon hormonal structure and function. This paper is considered to be the first report of a differential effect upon the agonist and receptor binding abilities of a glycoprotein hormone after modification of the proteinaceous, as opposed to the glycosylated, moiety of the molecule. PMID- 2584191 TI - Candida glabrata metallothioneins. Cloning and sequence of the genes and characterization of proteins. AB - Southern blot analysis has identified several metallothionein gene sequences in a human pathogenic yeast Candida glabrata. Two of these genes encoding proteins designated MT-I and MT-II have been cloned and sequenced. No introns were found in either of the genes. The complete primary structure of MT-II was also determined by protein sequencing methods. As isolated, MT-I and MT-II consist of 62 and 51 amino acids, respectively. The only residues predicted from the nucleotide sequence but not present in the isolated protein are the amino terminal methionines in each sequence. MT-I contains 18 cysteines, 14 of which are present as Cys-X-Cys motifs and two additional cysteines in a Cys-X-X-Cys sequence. The sequence of MT-II contains 16 cysteinyl residues, 14 of which are in Cys-X-Cys sequences. Fluorescence spectroscopy indicates the presence of Cu(I) thiolate bonds in both proteins. The binding stoichiometries are 11-12 for MT-I and 10 for MT-II. Under certain nutritional conditions, a truncated form of MT-II was also produced. Northern analysis of the total cellular RNA from copper treated cells showed that both MT-I and MT-II genes are regulated by this metal ion in a concentration-dependent fashion. The concentrations of MT-II mRNA appeared to be higher than that of MT-I mRNA at all concentrations of copper sulfate tested. Both genes are inducible by silver but not by cadmium salts. Cadmium ions, however, are effective in reducing the control levels of both MT-I and MT-II mRNAs. PMID- 2584192 TI - Type XII collagen. A large multidomain molecule with partial homology to type IX collagen. AB - Three overlapping cDNAs encoding alpha 1 (XII) collagen have been isolated and sequenced. The DNAs define five sequence domains within the chain. Three domains are nontriple-helical; two are relatively short triple-helical regions. The amino acid sequences of tryptic peptides derived from 16- and 10-kDa pepsin-resistant fragments isolated from tendon extracts are in full agreement with the deduced sequences of the triple-helical regions. Two of the five sequence domains in alpha 1 (XII), one triple-helical and one nontriple-helical, show a high degree of similarity to regions in type IX collagen chains. In addition, examination of seven exons in the alpha 1 (XII) gene shows that the gene is, in part, similar to the structure of type IX collagen genes. Therefore, collagen types IX and XII are partially homologous. The alpha 1 (XII) sequence data predict an asymmetric structure for type XII collagen molecules, fully consistent with the rotary shadowing images. These images show a triple-helical 75-nm tail attached through a central globule to three finger-like structures, each 60 nm long (Dublet, B., Oh, S., Sugrue, S. P., Gordon, M. K., Gerecke, D. R., Olsen, B. R., and van der Rest, M. (1989) J. Biol. Chem. 264, 13150-13156). PMID- 2584193 TI - Identification of rat S14 protein and comparison of its regulation with that of mRNA S14 employing synthetic peptide antisera. AB - The rat S14 gene encodes a protein of unknown function and has an amino acid sequence unrelated to any published sequences. Expression of mRNA S14 and lipogenesis in liver, fat, and mammary gland are regulated coordinately by dietary and hormonal stimuli, suggesting that the S14 protein may be associated with lipogenesis. Antisera to synthetic peptides corresponding to portions of the deduced amino acid sequence of the protein were used to identify the protein and to compare its regulation with that of mRNA S14. Antisera specifically recognized the in vitro translation product of mRNA S14 as defined by its migration on two dimensional gel electrophoresis. A product of identical Mr was identified on Western blots of liver homogenates from hyperthyroid, carbohydrate-fed rats. Subcellular fractionation showed that S14 protein is primarily cytosolic. The protein was detectable in tissues with abundant S14 gene expression, including hyperthyroid liver and epididymal fat and hypothyroid brown adipose tissue, whereas it was undetectable in hypothyroid liver and euthyroid kidney, testis, and spleen. Diurnal variation in hepatic mRNA S14 correlated with comparable changes in levels of the protein. Surprisingly, no S14 protein was observed in the livers of chronically (3 week) hypothyroid rats treated with triiodothyronine (T3) until 12 h had elapsed, despite attainment of maximal levels of mRNA S14 within 4 h. Rapid appearance of protein after T3 treatment was observed in both euthyroid and short term (4 day) hypothyroid rats, suggesting that long-term hypothyroidism is associated with a defect in the translational efficiency of mRNA S14. PMID- 2584194 TI - Kinetics of induction by thyroid hormone of the two hepatic mRNAs coding for cytosolic malic enzyme in the hypothyroid and euthyroid states. Evidence against an obligatory role of S14 protein in malic enzyme gene expression. AB - In rat liver, triiodothyronine (T3) and dietary carbohydrate induce the expression of the genes coding for malic enzyme (ME) (EC 1.1.1.40) and S14 protein. The mRNAs for both ME and S14 are elevated under circumstances associated with augmented lipogenesis. Since the lag time in the induction of mRNA coding for S14 is short (20 min) and the lag time in the induction of the mRNA for ME is relatively long (2-6 h), the possibility arose that the induction of the ME gene by T3 was mediated by S14 protein. To test this hypothesis we examined the temporal relationship between the accumulation of the hepatic S14 protein and the mRNAs coding for ME. In confirmation of previous reports, we found that two mRNAs coded for ME, one 27 S and the other 21 S in size. The level of enzyme activity generated appeared to be determined by both mRNA species. Sequencing of the 27 S fragment established that this mRNA is generated as a consequence of the use of an alternate polyadenylation site downstream to that used in the 21 S mRNA. Unanticipated from the earlier descriptions was the finding of a markedly asynchronous response of these mRNAs to T3 in hypothyroid animals. The lag time following T3 administration was 90 min for the 27 S and fully 8-12 h for the smaller 21 S sequence. Despite the rapid rise of mRNA S14, the S14 protein could not be detected for approximately 12 h after T3 administration. This ruled out the possibility that S14 is an obligate mediator in the induction of the ME gene. A contrasting pattern was observed in the euthyroid state where both ME mRNAs had indistinguishable lag times of 2-3 h, and the S14 protein rose within the same time frame. The delayed response of the 21 S mRNA for malic enzyme in hypothyroid animals thus appears to be due to a reversible defect in the transcription of the ME gene. PMID- 2584195 TI - Direct evidence that the glucocorticoid receptor binds to hsp90 at or near the termination of receptor translation in vitro. AB - We have translated the rat glucocorticoid receptor in both reticulocyte lysate and in wheat germ extract. Receptor synthesized in the reticulocyte lysate is immunoadsorbed by the 8D3 monoclonal antibody directed against the 90-kDa heat shock protein (hsp90) and it has a normal ability to bind glucocorticoid in a high affinity manner. Although the wheat germ extract synthesizes the full length receptor, the receptor is not immunoadsorbed by 8D3 and we cannot demonstrate high affinity steroid binding. Receptor synthesized by the reticulocyte lysate can be immunoadsorbed by antibody directed against hsp90 as soon as the translation product is full length, suggesting that the receptor becomes associated with hsp90 late during translation or immediately at the termination of translation. When newly synthesized receptor is bound with steroid and incubated at 25 degrees C, it is converted to a form that binds to DNA. This study provides direct evidence that association of hsp90 with the glucocorticoid receptor is a very early event and that the newly formed heteromeric receptor hsp90 complex is fully competent to undergo transformation. PMID- 2584196 TI - Endogenous epoxyeicosatrienoic acids. Cytochrome P-450 controlled stereoselectivity of the hepatic arachidonic acid epoxygenase. AB - Chiral analysis of the endogenous rat liver epoxyeicosatrienoic acids shows the biosynthesis of 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids in a 4:1, 2:1, and 3:1 ratio of antipodes, respectively. Animal treatment with phenobarbital results in a 3.7-fold increase in microsomal cytochrome P-450 concentration and a concomitant, regioselective 6.8- and 3.4-fold increase in the liver concentration of 8,9- and 14,15-epoxyeicosatrienoic acids, respectively. Phenobarbital induces the in vivo synthesis of both regioisomers as nearly optically pure enantiomers. These results demonstrate the enzymatic origin of the epoxyeicosatrienoic acids present in rat liver and document a novel metabolic function for cytochrome P-450 in the regio- and enatioselective epoxygenation of endogenous pools of arachidonic acid. PMID- 2584197 TI - Tissue-specific expression of the chicken alpha A-crystallin gene in cultured lens epithelia and transgenic mice. AB - The present experiments show that the single gene for the lens-specific protein alpha A-crystallin of chickens and mice uses a different subset of cis- and trans acting regulatory elements for expression in transfected embryonic chicken lens epithelial cells. A chicken alpha A-crystallin-chloramphenicol acetyltransferase (CAT) fusion gene required 162 base pairs whereas the murine alpha A-crystallin CAT fusion gene required only 111 base pairs of 5'-flanking sequences for efficient tissue-specific expression in the transfected chicken lens cells. Gel retardation and competition experiments were performed using embryonic chicken lens nuclear extract and oligodeoxynucleotides identical to the 5'-flanking region of the chicken (-170/-111) and murine (-111/-88 and -88/-55) alpha A crystallin gene. The results indicated that these homologous promoters use different nuclear factors for function. Methylation interference analysis identified a dyad of symmetry (CTGGTTCCCACCAG) at position -153 to -140 in the chicken alpha A-crystallin promoter which binds one or more lens nuclear factors. Gel mobility shift experiments using nuclear extracts of brain, reticulocytes, and muscle of embryonic chickens or HeLa cells suggested that the factor(s) binding to the chicken alpha A-crystallin gene promoter sequences are not lens specific. Despite differences in the functional and protein-binding properties of the alpha A-crystallin gene promoter of chickens and mice, expression of the chicken alpha A-crystallin-CAT fusion gene in transgenic mice was lens specific, consistent with a common underlying mechanism for expression of the alpha A crystallin gene in chickens and mice. PMID- 2584198 TI - The pathway of myo-inositol 1,3,4-trisphosphate phosphorylation in liver. Identification of myo-inositol 1,3,4-trisphosphate 6-kinase, myo-inositol 1,3,4 trisphosphate 5-kinase, and myo-inositol 1,3,4,6-tetrakisphosphate 5-kinase. AB - Inositol 1,3,4-trisphosphate (Ins(1,3,4)P3) metabolism has been studied in liver homogenates and in 100,000 x g supernatant and particulate fractions. When liver homogenates were incubated in an "intracellular" medium containing 5 mM MgATP, equal proportions of Ins(1,3,4)P3 were dephosphorylated and phosphorylated. Two inositol tetrakisphosphate (InsP4) products and an inositol pentakisphosphate (InsP5) were detected. The InsP4 isomers were unequivocally identified as inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) and inositol 1,3,4,6 tetrakisphosphate (Ins(1,3,4,6)P4) by high performance liquid chromatography separation of inositol phosphates, periodate oxidation, alkaline hydrolysis, and stereo-specific polyol dehydrogenase. Ins(1,3,4)P3 5-kinase is a novel enzyme activity and accounted for 16% of the total Ins(1,3,4)P3 phosphorylation. Ins(1,3,4,6)P4 was also shown to be further phosphorylated to inositol 1,3,4,5,6 pentakisphosphate (Ins(1,3,4,5,6)P5) by a kinase not previously known to occur in liver. About 75% of Ins(1,3,4)P3 kinase activities were soluble and were partly purified by anion-exchange fast protein liquid chromatography. The two Ins(1,3,4)P3 kinase activities eluted as a single peak that was well resolved from Ins(1,3,4)P3 phosphatase, Ins(1,3,4,6)P4 5-kinase, and Ins(1,3,4,5)P4 5 phosphatase activities. A further novel observation was that 10 microM Ins(1,3,4,5)P4 inhibited Ins(1,3,4)P3 kinase activities by 60%. PMID- 2584199 TI - Transglycosylation and transfer reaction activities of endo-alpha-N-acetyl-D galactosaminidase from Diplococcus (Streptococcus) pneumoniae. AB - Endo-alpha-N-acetyl-D-galactosaminidase from Diplococcus pneumoniae was shown to have transglycosylation and transfer reaction (reversed hydrolysis) activities. Treatment of asialoglycoproteins having Gal beta 1----3GalNAc alpha 1----Ser/Thr linkages with enzyme preparations containing glycerol resulted in formation of nonreducing trisaccharides. The structure of the main trisaccharide (approximately 80%) was deduced to be Gal beta 1----3GalNAc alpha 1----1(3) glycerol by analysis of sugar composition and the results of exoglycosidase treatment and periodate oxidation. The ability of the endoglycosidase to catalyze transfer of Gal beta 1----3GalNAc to various acceptors was also demonstrated by incubation of the enzyme with the disaccharide and the test compound. The following were found to show acceptor activity: glycerol, Tris, p-nitrophenol, threonine, serine, D-glucose, D-galactose, D-fucose, and 6-O-methylgalactose. Transfer to the primary hydroxyl groups of glycerol and hexoses appears to be favored since the major glycerol product was 1(3)-substituted and transfer to D fucose and 6-O-methyl-D-galactose was less than that to D-galactose. In order to avoid spurious results, it is necessary to carry out incubations with this enzyme in the absence of glycerol and other hydroxy compounds. The potential use of this endoglycosidase in the synthesis of glycosides is indicated by our studies. PMID- 2584200 TI - Purification and characterization of the adenosine A2-like binding site from human placental membrane. AB - We have purified and characterized the adenosine A2-like binding site from human placental membranes. 5'-N-Ethylcarboxamido[2,8-3H]adenosine ([3H]NECA) binds to this site, with a Kd of 240 nM and a Bmax of 13.0 pmol/mg in human placental membranes. The adenosine A2-like binding site was purified after extraction from placental membranes with 0.1% 3-[(3-cholamidopropyl)dimethylammonio]-1 propanesulfonic acid. The purification included ammonium sulfate precipitation and concanavalin A, DEAE-Sephadex, and Sepharose 6B gel filtration chromatographies. The protein was purified 127-fold to homogeneity, with a final specific activity of 1.5-1.9 nmol/mg of protein and a 5.5-8.1% yield of binding activity from the membranes. The purified protein had similar binding properties and an identical potency order for displacement of [3H] NECA by adenosine analogs as the initial membranes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified protein revealed a single band at 98 kDa which coeluted with [3H]NECA binding activity during Sepharose 6B gel filtration chromatography. In 0.1% Triton X-100, the binding complex has a Stokes radius of 70 A, a sedimentation coefficient of 6.9 S, and a partial specific volume of 0.698 ml/g. The detergent-protein complex has a calculated molecular mass of 230 kDa. The estimated frictional ratio is 1.5. The native binding complex appears to consist of a dimer of identical subunits. The function of this ubiquitous protein remains unclear. PMID- 2584202 TI - Structure of phosphonoglycosphingolipid containing pyruvylated galactose in nerve fibers of Aplysia kurodai. AB - A phosphonoglycosphingolipid, designated as FGL-IIb, was identified in nerve fibers of Aplysia kurodai by two-dimensional thin layer chromatography (Abe, S., Araki, S., and Satake, M. (1986) Biomed. Res. (Tokyo) 7, 47-51). FGL-IIb was isolated from the nervous system of A. kurodai by Iatrobeads column chromatography using three solvent systems. Pyruvic acid was identified by thin layer chromatography as its 2,4-dinitrophenylhydrazone and established by permethylation studies to be attached as a ketal to O-3 and O-4 of the terminal galactose of the oligosaccharide chain in FGL-IIb. By sugar analysis, permethylation studies, fast atom bombardment-mass spectrometry, and proton magnetic resonance spectrometry, the structure of FGL-IIb was concluded to be [3,4-O-(1-carboxyethylidene)]Gal beta 1----3GalNAc alpha 1----3(Fuc alpha 1----2) (2-aminoethylphosphonyl----6)Gal beta 1----4Glc beta 1----1ceramide. Its major aliphatic components were palmitic acid, octadeca-4-sphingenine and anteisononadeca-4-sphingenine. This is the first report of the occurrence of pyruvylated galactose as a constituent of animal sphingolipid. PMID- 2584201 TI - Expression of the rat L-type pyruvate kinase gene from its dual erythroid- and liver-specific promoter in transgenic mice. AB - The gene for the L-type pyruvate kinase possesses two promoters which are located 500 base pairs apart. The L promoter is specific to liver and regulated by hormones and diet; the L' promoter is specific to erythroid cells. We produced two series of transgenic mice carrying either the entire rat L-pyruvate kinase gene or a minigene devoid of exons two to nine, with 2.7 kilobases of flanking sequences 5' to the cap site of the L' promoter and 1.4 kilobases 3' to the downstream polyadenylation site. In both series the patterns of expression from the two promoters were similar to those of the endogenous rat gene. The rat L promoter was expressed strongly in liver and weakly in kidney and gut of adult transgenic mice. Moreover, it was regulated like the endogenous rat L-pyruvate kinase gene upon hormonal and nutritional adaptation: the level of L-pyruvate kinase mRNA was decreased dramatically by 24 h of starvation, while refeeding a carbohydrate-rich diet strongly stimulated expression of the transgenes. This stimulation was prevented by glucagon. Use of alternative polyadenylation sites in the last exon of the rat L-type pyruvate kinase gene was similar for both types of transgenes and similar to that in rat and not control mice, suggesting that the transgenes contain the sequences that control the choice of polyadenylation site. Transcription of the minigene was higher than that of the entire transgene, probably due to the high copy number of the minigene. At the protein level, rat L subunits encoded by the entire transgene were more abundant than mouse subunits in the liver of adult transgenic mice. In contrast, expression of the rat L' promoter in fetal liver was only 5% of that in fetal rat liver, and we were unable to detect rat L' subunits of pyruvate kinase enzyme in the red blood cells from transgenic mice. Our results suggest that the integrated DNA contains all elements necessary for tissue specificity (L' and L) as well as hormonal and nutritional control (L) of expression of the rat transgene. Nevertheless, a L'-specific activating element may be missing. PMID- 2584203 TI - Identification of an 18,000-dalton protein in mammalian lens fiber cell membranes. AB - Monoclonal antibodies have been produced against electrophoretically purified MP18, a major calf lens membrane Mr = 18,000 substrate for cAMP-dependent protein kinase. One of these antibodies (monoclonal antibody 2D10) cross-reacted with both native MP18 in lens membranes, and sodium dodecyl sulfate-denatured, electrophoretically purified MP18. In immunoblots, this antibody recognized MP18 in pig, sheep, rat, human, but not chicken lens membranes, indicating the similarity of this protein in mammalian lenses. Amino acid sequencing revealed that the N-terminal sequence of MP18 is identical in these five different mammalian species and is unrelated to any previously sequenced lens or junctional proteins. Electron microscopic examination of monoclonal antibody 2D10-labeled bovine, pig and rat lens membranes indicated that MP18 is localized exclusively to the thicker 16-17 nm junctions in isolated preparations of lens fiber cell membranes. These results provide evidence of a role for MP18 in mammalian lens fiber cell junctional organization. PMID- 2584205 TI - Human vascular permeability factor. Isolation from U937 cells. AB - Human vascular permeability factor (hVPF) is a glycoprotein that promotes fluid and protein leakage from blood vessels. The function of hVPF is at present unknown, but the potent bioactivities of this protein suggest that it could act during inflammation, wound healing, and tumor angiogenesis. hVPF was purified from serum-free conditioned medium of the human histiocytic lymphoma cell line U937 as a disulfide-linked dimeric 40-kDa protein that promoted dermal blood vessel leakage in guinea pigs at a dose of 20 ng (3 x 10(-9) M) and promoted in vitro endothelial cell growth at concentrations as low as 50 PM. Multiple forms of hVPF with apparent pI values greater than 7.5 were resolved using pH gradient electrophoresis. Antibodies against guinea pig vascular permeability factor were found to cross-react with hVPF. The N-terminal amino acid sequence of hVPF was similar to, but not identical with, the N-terminal sequence of guinea pig vascular permeability factor. PMID- 2584204 TI - Structural organization of the lens fiber cell plasma membrane protein MP18. AB - The 18,000-dalton bovine lens fiber cell intrinsic membrane protein MP18 was phosphorylated on a serine residue by both cAMP-dependent protein kinase and protein kinase C. In addition, this protein bound calmodulin and was recognized by a monoclonal antibody (2D10). These different regions were localized using enzymatic and chemical fragmentation of electrophoretically purified MP18 that had been phosphorylated with either cAMP-dependent protein kinase or protein kinase C. Partial digestion of 32P-labeled MP18 with protease V8 resulted in a Mr = 17,000 peptide that bound calmodulin, but neither contained 32P or was recognized by the monoclonal antibody 2D10. Furthermore, the 17-kDa peptide had the same N-terminal amino acid sequence as MP18. Thus, the monoclonal antibody 2D10 recognition site and the protein kinase phosphorylation site(s) are close together and confined to a small region in the C terminus of MP18. This conclusion was confirmed in experiments where MP18 was fragmented with trypsin, endoproteinase Lys-C, or CNBr. The location of the phosphorylation site was confirmed by sequencing the small 32P-labeled, C-terminal peptide that resulted from protease V8 digestion of 32P-labeled MP18. This peptide contained a consensus sequence for cAMP-dependent protein kinase. PMID- 2584207 TI - Bone sialoprotein II synthesized by cultured osteoblasts contains tyrosine sulfate. AB - Isolated mouse osteoblasts that retain their osteogenic activity in culture were incubated with [35S] sulfate. Two radiolabeled proteins, in addition to proteoglycans, were extracted from the calcified matrix of osteoblast cultures. All the sulfate label in both proteins was in the form of tyrosine sulfate as assessed by amino acid analysis and thin layer chromatography following alkaline hydrolysis. The elution behavior on DEAE-Sephacel of the major sulfated protein and the apparent Mr on sodium dodecyl sulfate gels were characteristic of bone sialoprotein II extracted from rat. This protein was shown to cross-react with an antiserum raised against bovine bone sialoprotein II, indicating that bone sialoprotein II synthesized by cultured mouse osteoblasts is a tyrosine-sulfated protein. The minor sulfated protein was tentatively identified as bone sialoprotein I or osteopontin based on its elution properties on DEAE-Sephacel and anomalous behavior on sodium dodecyl sulfate gels similar to those reported for rat bone sialoprotein I. PMID- 2584206 TI - Tissue-specific forms of type IX collagen-proteoglycan arise from the use of two widely separated promoters. AB - We demonstrate that the gene encoding an extracellular matrix component contains two widely separated promoters controlling the generation of different transcripts in a tissue-specific fashion. Two transcription start sites, about 20 kilobase pairs apart, in the alpha 1(IX) collagen gene are utilized to generate different forms of a collagen-proteoglycan (collagen IX) in chicken cartilage and cornea. Transcripts from the upstream site encode a large (266 amino acid residues) globular domain at the amino terminus of alpha 1(IX) chains, whereas the transcripts from the downstream site encode chains that lack this globular domain and contain a short alternative sequence. Transcripts from the upstream site are predominantly present in cartilage, and transcripts from the downstream site are predominantly used in cornea. The structural differences in collagen IX molecules that are synthesized as a consequence of the use of these two alternative transcription start sites in the alpha 1(IX) gene are likely to contribute to the differences in the macromolecular organization of the extracellular matrix in cartilage and cornea. Our finding provides a novel clue to answering the general question of what mechanisms are used to generate unique fibrillar patterns in different tissues. PMID- 2584209 TI - A mutation in the catalytic subunit of protein kinase A prevents myristylation but does not inhibit biological activity. AB - The catalytic of subunit of cAMP-dependent protein kinase is acylated at its NH2 terminus with myristic acid. This type of modification is thought to mediate the association of proteins with lipid bilayers, yet the catalytic subunit shows no preferential binding with membranes. We investigated the role of C subunit myristylation using a cDNA expression vector in which the acylated NH2-terminal Gly was mutagenized to Ala. Protein synthesized in NIH 3T3 cells from this modified gene did not incorporate [3H]myristate. However, the kinase activity of this altered C subunit on a synthetic substrate was not diminished, nor was its ability to form holoenzyme with regulatory subunit. Non-myristylated C subunit also regulated several biological processes occurring in specific subcellular compartments; mutant C subunit stimulated dramatic cell shape changes controlled by the cytoskeleton, restored steroidogenesis in the mitochondria of defective adrenocortical cells, and effectively induced the transcription of genes in the nucleus. These results suggest that myristylation is nonessential for C subunit conformation and enzyme activation, and is not required for C subunit interaction with other proteins in regions where C is thought to localize upon activation. The purpose for NH2-terminal myristylation of this important signal-transducing enzyme remains an enigma. PMID- 2584208 TI - Isolation and molecular cloning of mast cell carboxypeptidase A. A novel member of the carboxypeptidase gene family. AB - Mast cell carboxypeptidase A has been isolated from the secretory granules of mouse peritoneal connective tissue mast cells (CTMC) and from a mouse Kirsten sarcoma virus-immortalized mast cell line (KiSV-MC), and a cDNA that encodes this exopeptidase has been cloned from a KiSV-MC-derived cDNA library. KiSV-MC-derived mast cell carboxypeptidase A was purified with a potato-derived carboxypeptidase inhibitor affinity column and was found by analytical sodium dodecyl sulfate polyacrylamide gel electrophoresis to be a Mr 36,000 protein. Secretory granule proteins from KiSV-MC and from mouse peritoneal CTMC were then resolved by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transblotted to polyvinylidine difluoride membranes. Identical aminoterminal amino acid sequences were obtained for the prominent Mr 36,000 protein present in the granules of both cell types. Based on the amino-terminal sequence, an oligonucleotide probe was synthesized and used to isolate a 1,470-base pair cDNA that encodes this mouse exopeptidase. The deduced amino acid sequence revealed that, after cleavage of a 15-amino acid hydrophobic signal peptide and a 94-amino acid activation peptide from a 417-amino acid preproenzyme, the mature mast cell carboxypeptidase A protein core has a predicted Mr of 35,780 and a high positive charge [Lys + Arg) - (Asp + Glu) = 17) at neutral pH. Although critical zinc binding amino acids (His67, Glu70, His195), substrate-binding amino acids (Arg69, Asn142, Arg143, Tyr197, Asp255, Phe278), and cysteine residues that participate in intrachain disulfide bonds (Cys64-Cys77, Cys136-Cys159) of pancreatic carboxypeptidases were also present in mast cell carboxypeptidase A, the overall amino acid sequence identities for mouse mast cell carboxypeptidase A relative to rat pancreatic carboxypeptidases A1, A2, and B were only 43, 41, and 53%, respectively. RNA and DNA blot analyses revealed that mouse peritoneal CTMC, KiSV MC, and bone marrow-derived mast cells all express a prominent 1.5-kilobase mast cell carboxypeptidase A mRNA which is transcribed from a single gene. We conclude that mouse mast cell carboxypeptidase A is a prominent secretory granule enzyme of mast cells of the CTMC subclass and represents a novel addition to the carboxypeptidase gene family. PMID- 2584210 TI - Receptor-stimulated phospholipase A2 activation is coupled to influx of external calcium and not to mobilization of intracellular calcium in C62B glioma cells. AB - C62B rat glioma cells respond to muscarinic cholinergic stimulation with transient inositol phosphate formation and phospholipase A2-dependent arachidonic acid liberation. Since phospholipase A2 is a Ca2+-sensitive enzyme, we have examined the role of the agonist-stimulated Ca2+ response in production of the arachidonate signal. The fluorescent indicator fura-2 was used to monitor changes in cytoplasmic Ca2+ levels ([Ca2+]i) of C62B cells following acetylcholine treatment. In the presence of extracellular Ca2+, acetylcholine induces a biphasic [Ca2+]i response consisting of an initial transient peak that precedes arachidonate liberation and a sustained elevation that outlasts the phospholipase A2 response. The initial [Ca2+]i peak is not altered by the absence of external Ca2+ and therefore reflects intracellular Ca2+ mobilization. The sustained elevation phase is dependent on the influx of external Ca2+; it is lost in Ca2+ free medium and restored on the addition of Ca2+. Pretreating cells with phorbol dibutyrate substantially inhibits acetylcholine-stimulated inositol phosphate formation and the peak [Ca2+]i response without affecting the sustained elevation in [Ca2+]i. This suggests that the release of internal Ca2+ stores by inositol 1,4,5-trisphosphate can be blocked without interfering with Ca2+ influx. Pretreatment with phorbol also fails to affect acetylcholine-stimulated arachidonate liberation, demonstrating that phospholipase A2 activation does not require normal intracellular Ca2+ release. Stimulated arachidonate accumulation is totally inhibited in Ca2+-free medium and restored by the subsequent addition of Ca2+. Pretreatment with verapamil, a voltage-dependent Ca2+ channel inhibitor, also blocks both the sustained [Ca2+]i elevation and arachidonate liberation without altering peak intracellular Ca2+ release. We conclude that the influx of extracellular Ca2+ is tightly coupled to phospholipase A2 activation, whereas large changes in [Ca2+]i due to mobilization of internal Ca2+ stores are neither sufficient nor necessary for acetylcholine-stimulated phospholipase A2 activation. PMID- 2584211 TI - Specific interaction between gangliotriaosylceramide (Gg3) and sialosyllactosylceramide (GM3) as a basis for specific cellular recognition between lymphoma and melanoma cells. AB - In view of the possible role of glycosphingolipids in defining the specificity of cell-cell interactions, the key molecules for recognition of cell surface glycosphingolipids have been studied. In addition to previously suggested recognition mechanisms involving endogenous lectins and glycosyltransferases, an alternative possibility, based on carbohydrate-carbohydrate (Lex-Lex) interaction, has been raised (Eggens, I., Fenderson, B., Toyokuni, T., Dean, B., Stroud, M., and Hakomori, S. (1989) J. Biol. Chem. 264, 9476-9484). We now report a highly specific interaction between gangliotriaosylceramide (Gg3, GalNAc beta 1 ---4Gal beta 1----4Glc beta 1----Cer) and sialosyllactosylceramide (GM3, NeuAc alpha 2----3Gal beta 1----4Glc beta 1----Cer). The interaction requires a bivalent cation (Ca2+ or Mg2+) and can be inhibited by sialosyl 2----3 lactose, anti-GM3 antibody (DH2), anti-Gg3 antibody (2D4), or EDTA. The strength of interaction between GM3 liposome and the Gg3-coated plastic surface was highly density-dependent. The mouse lymphoma L5178 AA12 cell line (high expressor of Gg3) interacted specifically with the mouse B16 melanoma cell line (high expressor of GM3). The interaction was inhibited by 5 mM sialosyllactose, anti GM3 antibody, anti-Gg3 antibody, and EDTA in analogy to GM3-Gg3 interaction. L5178 AV27, a genetically related variant clone which does not express Gg3, showed no interaction with B16 cells. Untreated AA12 cells, but not 2D4-treated AA12 cells or AV27 cells, interacted with GM3 coated on the plastic surface. These findings suggest a specific interaction between AA12 cells and B16 cells based on Gg3-GM3 interaction. PMID- 2584212 TI - A 165-base pair sequence between the dihydrofolate reductase gene and the divergently transcribed upstream gene is sufficient for bidirectional transcriptional activity. AB - The dihydrofolate reductase gene encodes a key enzyme of one-carbon metabolism and is constitutively expressed in all cells. Recently, transcripts initiated at 89 base pairs upstream from the transcriptional initiation site of the dihydrofolate reductase gene and transcribed from the opposite strand have been identified and shown to encode for a protein with homology to a bacterial DNA mismatch repair enzyme (Fujii, H., and Shimada, T. (1989) J. Biol. Chem. 264, 10057-10064). Therefore, the two genes are organized in a head-to-head configuration separated by an 89-base pair segment. The promoter activities of this short spacer sequence were studied in a transient assay using the chloramphenicol acetyltransferase and the guanine phosphoribosyltransferase genes as reporters. A 165-base pair fragment from -111 to +54 relative to the dihydrofolate reductase initiation site was shown to be sufficient for transcriptional activity in either direction, suggesting that expression of the two divergent genes is regulated by a bidirectional promoter that may use common regulatory elements. PMID- 2584213 TI - Development expression of the genes encoding the four subunits of the chicken muscle acetylcholine receptor. AB - Subunit-specific DNA probes for the chicken muscle acetylcholine receptor have been used in conjunction with Northern blots and dot-blots based upon the SP6/T7 RNA polymerase reaction to quantitate changes in the steady-state mRNA levels of all four subunits during development. In pectoral muscle, maximal subunit transcript levels are observed at day 12 in ovo for alpha, days 12-16 in ovo for beta, day 14 in ovo for gamma, and days 12-14 in ovo for delta. Interestingly, two delta-subunit transcripts which have somewhat different patterns of temporal expression are detected. At the peak of expression of each subunit mRNA the absolute levels of the alpha-, beta-, and gamma-subunit transcripts are very similar (49.2, 66.0, and 70.7 attomoles of transcript/micrograms of poly(A)+ RNA, respectively) whereas that for the summed delta-subunit transcripts is significantly lower (17.8 attomoles/micrograms of poly(A)+ RNA). Further, this lower level of delta-subunit mRNA is observed from day 10 to day 16 of embryonic development. We conclude that subunit transcript availability is important in the synthesis of acetylcholine receptor protein during development and that the level of the delta-subunit transcript can be rate limiting in the expression of this receptor. PMID- 2584214 TI - The carboxyl terminus of the chicken alpha 3 chain of collagen VI is a unique mosaic structure with glycoprotein Ib-like, fibronectin type III, and Kunitz modules. AB - The primary amino acid sequence of the carboxyl-terminal portion of the alpha 3 chain of chick type VI collagen as deduced from the nucleotide sequence is reported. This carboxyl-terminal segment is not present in the alpha 1 and alpha 2 chains of chick type VI collagen and is specific for a mosaic region with extensive similarities to several other proteins. This unique segment, beginning with a stretch (73 residues) very rich in serine and threonine, is preceded by sequences analogous to the platelet glycoprotein Ib. This region is followed by one segment that closely resembles the type III domains of fibronectin. At the end of the sequence, there is a 58-residue motif very similar to sequences characteristic of the Kunitz-type proteinase inhibitors. The present findings and our recent observation that the alpha 3(VI) chain contains 11 repeats similar to type A repeats of von Willebrand factor raise interesting questions about the peculiar mosaic structure and the multiple functions that this unique collagen might play in growth and remodeling of connective tissues. PMID- 2584215 TI - Gastrotropin: not an enterooxyntin but a member of a family of cytoplasmic hydrophobic ligand binding proteins. AB - Gastrotropin, a peptide initially isolated from porcine intestinal extracts, has been proposed to be an enterooxyntin. We have isolated a full length gastrotropin cDNA from a hog small intestinal lambda gt11 library. No evidence of co translational translocation or processing of the encoded 127-residue protein could be demonstrated using an in vitro transcription/translation/microsomal processing assay. Comparative sequence analyses indicate that gastrotropin is a new member of the family of cytoplasmic hydrophobic ligand proteins. Analysis of the distribution of gastrotropin in nine adult Sprague-Dawley rat tissues revealed that the gene is expressed in small intestine but not in stomach, liver, heart, skeletal muscle, lung, kidney, adrenals, or brain. Bioactivity studies demonstrated that neither gastrotropin nor a carboxyl-terminally amidated tridecapeptide fragment deduced from the cDNA sequence influence acid secretory activity in rats with gastric fistulas or in isolated canine gastric parietal cells. Together these data suggest that gastrotropin is not likely to be secreted as a hormone or to function as an enterooxyntin. Moreover, it appears that gastrotropin represents one of several members of the family of hydrophobic ligand binding proteins that are expressed in the small intestine. PMID- 2584216 TI - Overexpression of the type II regulatory subunit of the cAMP-dependent protein kinase eliminates the type I holoenzyme in mouse cells. AB - Mammalian tissues and cell lines express two major types of cAMP-dependent protein kinase, PKA-I and PKA-II, which can be distinguished at the molecular level by the presence of either type I or type II regulatory subunits in the holoenzyme. An expression vector for the mouse type II regulatory subunit (RII alpha) was transfected into ras-transformed NIH3T3 (R3T3) cells, which contain approximately equal amounts of both holoenzymes, PKA-I and PKA-II. In RII alpha overexpressing R3T3 cells, PKA-II levels were increased, and the level of PKA-I declined. The decrease in PKA-I was dependent on the amount of RII alpha expressed, and at high levels of RII alpha expression, PKA-I was completely eliminated. In contrast, overexpression of the type I regulatory subunit (RI alpha) did not alter PKA isozyme levels. We propose that competition between RII alpha and RI alpha for a limited pool of catalytic subunit results in preferential assembly of PKA-II and that significant amounts of PKA-I are formed only if catalytic subunit is present in excess of the RII alpha subunit. The PKA I isozyme, which is absent in untransformed 3T3 cells, is not essential for the transformed phenotype of R3T3 cells. RII alpha-overexpressing R3T3 cells that are devoid of PKA-I continued to exhibit a transformed phenotype including anchorage independent growth. Overexpression of RII alpha provides a genetic approach that may prove useful in demonstrating specific functions for the two PKA isozymes in cAMP-dependent signal transduction pathways. PMID- 2584217 TI - Heparin-modulated binding of pancreatic lipase and uptake of hydrolyzed triglycerides in the intestine. AB - Utilizing small intestine membranes that contain heparin (50 micrograms/mg protein), binding of triglyceride lipase (homogeneous 52 kDa, specific activity, 70 nmol/mg.h) to membranes was shown to be concentration dependent and saturable, and it was characterized by a single dissociation constant (KD = 86 +/- 16 nM) with a maximal binding capacity of 54 +/- 8 pmol/mg of vesicle protein. Specific binding was decreased in a concentration-dependent manner by the addition of exogenous heparin, and binding was virtually eliminated (less than 6% control values) by pretreatment of membranes with bacterial heparinase. Cultured intestinal epithelial cells (CaCo-2), shown to possess membrane-associated heparin, also bound pancreatic triglyceride lipase in a specific and saturable manner, with KD = 77 +/- 12 nM and Bmax = 13.7 +/- 6 pmol/10(6) cells. Soluble heparin not only decreased binding, but it also diminished the enzyme-mediated cellular uptake of [14C]oleate from [14C]triolein by over 75%. Therefore, intestinal heparin, a component of the brush border membrane, localizes pancreatic triglyceride lipase in a receptor-like manner to the plasma membrane to promote the subsequent absorption of fatty acids derived from hydrolyzed triglycerides. PMID- 2584218 TI - Protein structural requirements and properties of membrane binding by gamma carboxyglutamic acid-containing plasma proteins and peptides. AB - The membrane-binding characteristics of a number of modified vitamin K-dependent proteins and peptides showed a general pattern of structural requirements. The amino-terminal peptides from human prothrombin (residues 1-41 and 1-44, 60:40) bovine factor X (residues 1-44), and bovine factor IX (residues 1-42), showed a general requirement for a free amino-terminal group, an intact disulfide, and the tyrosine homologous to Tyr44 of factor X for membrane binding. Consequently, the peptide from factor IX did not bind to membranes. Any of several modifications of the amino terminus, except reaction with trinitrobenzenesulfonic acid, abolished membrane binding by the factor X and prothrombin peptides. Calcium, but not magnesium, protected the amino terminus from chemical modification. The requirement for a free amino terminus was also shown to be true for intact prothrombin fragment 1, factor X, and factor IX. Although aggregation of the peptide-vesicle complexes greatly complicated accurate estimation of equilibrium binding constants, results with the factor X peptide indicated an affinity that was not greatly different from that of the parent protein. The most striking difference shown by the peptides was a requirement for about 10 times as much calcium as the parent proteins. In a manner similar to the parent proteins, the prothrombin and factor X peptides showed a large calcium-dependent quenching of tryptophan fluorescence. This fluorescence quenching in the peptides also required about 10 times the calcium needed by the parent proteins. Thus, the 1-45 region of the vitamin K-dependent proteins contained most of the membrane-binding structure but lacked component(s) needed for high affinity calcium binding. Protein S that was modified by thrombin cleavage at Arg52 and Arg70 showed approximately the same behavior as the amino-terminal 45-residue peptides. That is, it bound to membranes with overall affinity that was similar to native protein S but required high calcium concentrations. These results suggested that the second disulfide loop of protein S (Cys47-Cys72) and prothrombin (Cys48 Cys61) were involved in high affinity calcium binding. Since factor X lacks a homologous disulfide loop, an alternative structure must serve a similar function. A striking property of protein S was dissociation from membranes by high calcium. While this property was shared by all the vitamin K-dependent proteins, protein S showed this most dramatically and supported protein-membrane binding by calcium bridging. PMID- 2584220 TI - Phosphorylation of lignin peroxidases from Phanerochaete chrysosporium. Identification of mannose 6-phosphate. AB - Many of the extracellular lignin-degrading peroxidases from the wood-degrading fungus Phanerochaete chrysosporium are phosphorylated. Immunoprecipitation of the extracellular fluid of cultures grown with H2K32PO4 with a polyclonal antibody raised against one of the lignin peroxidase isozymes, H8 (pI 3.5), revealed the incorporation of H2K32PO4 into lignin peroxidases. Analyses of the purified isozymes from labeled cultures by isoelectric focusing showed that, in addition to isozyme H8, lignin peroxidase isozymes H2 (pI 4.4), H6 (pI 3.7), and H10 (pI 3.3) are also phosphorylated. These analyses also showed that lignin peroxidase isozyme H1 (pI 4.7) and manganese-dependent peroxidase isozymes H3 (pI 4.9) and H4 (pI 4.5) are not phosphorylated. Phosphate quantitation indicated the presence of one molecule of phosphate/molecule of enzyme for all of the phosphorylated isozymes. To locate the site of phosphorylation, one-dimensional phosphoamino acid analysis was performed with hydrolyzed 32P-protein. However, phosphotyrosine, phosphoserine, and phosphothreonine could not be identified. Coupled enzyme assays of acid hydrolysate indicated the presence of mannose 6 phosphate as the phosphorylated component on the lignin peroxidase isozymes. Digestion of the isozymes with N-glycanase released the phosphate component, indicating that the mannose 6-phosphate is contained on an asparagine-linked oligosaccharide. PMID- 2584219 TI - The reactivity of sulfhydryl groups of bovine cardiac troponin C. AB - Bovine cardiac troponin C (cTnC) contains 2 cysteine residues, Cys-35 located in the nonfunctional Ca2+-binding loop I and Cys-84 in the N-terminal segment of the central helix. We have studied the reactivity of Cys residues in cTnC with 5,5' dithiobis(2-nitrobenzoic acid) (DTNB) and 7-diethylamino-3-(4'-maleimidylphenyl) 4-methylcoumarin (CPM). The latter compound fluoresces only when reacted with the protein. The reaction with DTNB followed second order kinetics with respect to DTNB, the rate constants being 3.37 s-1 M-1 and 1.82 s-1 M-1 in the presence and absence of Ca2+, respectively. These rates are much slower than the rate of reaction with Cys-98 of skeletal TnC (sTnC) or with the urea-denatured cTnC, indicating that both Cys residues are partly buried within the structure of the protein. The increase in reactivity was induced by binding of Ca2+ to the single low affinity Ca2+ binding site (site II). The fluorescence increase upon reaction of cTnC with CPM in the absence of Ca2+ could be fitted with a single exponential equation indicating that both cysteine residues are equally available to the reagent. The reaction in the presence of Ca2+ was biphasic. Analysis of CNBr fragments of cTnC labeled with CPM under various conditions indicated that in the presence of Ca2+ the reactivity of Cys-84 is increased while that of Cys-35 is slightly decreased. This finding is consistent with the model of Herzberg et al. (Herzberg, O., Moult, J., and James, M. N. G. (1986) J. Biol. Chem. 261, 2638 2644) and the data of Ingraham and Hodges (Ingraham, R. H., and Hodges, R. S. (1988) Biochemistry 27, 5891-5898), suggesting that the Ca2+-induced conformational change in the N-terminal half of TnC involves separation of the helix C from the central helix, thereby increasing the accessibility of Cys-84. The slow overall kinetics, however, indicates that the structure in the vicinity of Cys residues is relatively compact regardless of Ca2+. We interpret the increase in reactivity towards CPM as consistent with a Ca2+-induced exposure of a hydrophobic pocket in the vicinity of Cys-84. PMID- 2584221 TI - Identification and characterization of a novel transcription factor participating in the expression of eukaryotic initiation factor 2 alpha. AB - We have recently cloned and characterized the promoter region of the gene encoding eukaryotic initiation factor 2 alpha (eIF-2 alpha) to identify regulatory elements of this housekeeping gene. We compared the location of DNase I-hypersensitive (HS) sites with the distribution of protein-binding sites as revealed by footprint analysis. The eIF-2 alpha promoter contains four upstream DNase I-HS sites extending from -650 to -40 base pairs and a fifth downstream site near the first intron-exon junction. In vitro DNase I footprint analysis shows eight distinct DNA-protein interactions organized into clusters that correspond well with the distribution of the five HS sites. None of the protected regions, however, shares obvious sequence homology with the binding sites of known regulatory factors. To initiate our analysis of factors required for eIF-2 alpha expression, selected a CAP-proximal element shown by in vivo methylation protection analysis to bind a potential regulatory factor. A striking feature of this element is its palindrome sequences and eight-base pair direct repeats. We have purified to near homogeneity a 66-68-kDa protein that binds to this region and have designated it alpha-PAL. The alpha-PAL-binding site extends from -74 to 10. By methylation protection analysis and mobility shift assay, the alpha-PAL binding site is shown to be two adjacent sites, one with high and one with lower affinity, which bind alpha-PAL in a noncooperative manner. When the high affinity binding site is cloned upstream of the adenovirus 2 core promoter, in vitro transcription is stimulated 2-3-fold. When linked to a CAT reporter gene, activity of the eIF-2 alpha promoter shows an approximate 2-fold dependence on the alpha-PAL element. PMID- 2584222 TI - Cooperative DNA binding by Xenopus transcription factor IIIA. Use of a 66-base pair DNA fragment containing the intragenic control region of the 5 S RNA gene to study specific and nonspecific interactions. AB - The interaction of Xenopus transcription factor IIIA (TFIIIA) with a synthetic 66 base pair DNA fragment containing the intragenic control region (ICR) of the 5 S RNA gene was investigated by mobility shift gel electrophoresis and DNase I protection experiments. Specific EDTA-sensitive protein-DNA complexes were observed only in the presence of high concentrations of either the ICR-containing fragment or an excess of unlabeled nonspecific DNA. This predominant complex was determined to be composed of equal molar ratios of TFIIIA and the 66-base pair ICR-containing fragment, although complexes containing two TFIIIA molecules/ICR and three TFIIIA molecules/ICR were also found. In the absence of excess unlabeled specific or nonspecific DNA, TFIIIA was observed to interact with the labeled 66-mer as an aggregate that remained at the top of the gel matrix. Although the binding affinities of TFIIIA for the 66-base pair specific DNA fragment and the 74-base pair nonspecific DNA fragment were comparable as observed by direct measurement with mobility shift gel electrophoresis, a greater than 500-fold difference was observed by competition experiments at high DNA concentrations. Furthermore, a similar difference was also detected when proteolytically cleaved TFIIIA was used in the binding reaction, which substantially reduced the protein-protein interactions. DNase I digestion patterns of the noncoding strand of the 66-mer in the absence or presence of TFIIIA demonstrated that this region of DNA is structurally equivalent to the ICR contained within the 5 S RNA gene. In addition, the mode of binding observed in the mobility shift gels is identical to that observed by direct footprint analysis. Protein-protein interactions appear, therefore, to be an intrinsic and necessary activity of TFIIIA. PMID- 2584223 TI - Structure of the promoter region and tissue specificity of the human glycophorin C gene. AB - Glycophorin C (GPC) is an integral membrane protein of human erythrocytes which plays an important role in regulating the deformability and mechanical stability of red cells. Recently, the structural gene for this glycoprotein has been cloned (Colin, Y., Le Van Kim, C., Tsapis, A., Clerget, M., d'Auriol, L., London, J., Galibert, F., and Cartron, J. P. (1989) J. Biol. Chem. 264, 3773-3780), and we have now determined the sequence of the 1050 base pairs of DNA preceding the transcription initiation site mapped in erythroid cells. This region contains different potential regulatory cis-acting elements found in a variety of eukaryotic promoters (TATA box, CAAT box, Sp1-binding site) as well as sequences present in the promoter and enhancer regions of genes specific for the erythroid lineage (CACCC box and NF-E1-binding site). Northern blot analysis and immunological studies indicate that the GPC gene is expressed in a large number of cells and tissues. However, the level of transcription as well as the glycosylation of the mature GPC differ in erythroid and nonerythroid cells. Primer extension analysis and mapping of the 5' end GPC mRNA by the polymerase chain reaction indicate that different transcription sites are utilized for the expression of the GPC gene in erythroid and nonerythroid tissues and cell lines. PMID- 2584224 TI - Regulation of the gene for estrogenic 17-ketosteroid reductase lying on chromosome 17cen----q25. AB - 17-Ketosteroid reductase (17KSR), also known as 17 beta-hydroxysteroid dehydrogenase, catalyzes the reversible interconversion of estradiol to estrone and of androstenedione to testosterone. Using a recently cloned human placental 17KSR cDNA, we show that the 1.4-kilobase mRNA for this enzyme is detected only in tissues producing estrogens, and a 2.4-kilobase mRNA is detected in some estrogenic tissues and some androgenic tissues. This tissue distribution suggests that the interconversion of androstenedione and testosterone may be mediated by a different enzyme. Southern blotting studies show that the mRNA for this estrogenic 17KSR is encoded by two very similar genes localized to chromosome 17cen----q25 by analysis of DNA from mouse/human somatic hybrid cell lines. 8-Br cAMP increases the abundance of estrogenic 17KSR mRNA as well as mRNAs for other steroidogenic enzymes in JEG-3 choriocarcinoma cells. By contrast, cAMP decreases estrogenic 17KSR mRNA in primary cultures of human cytotrophoblasts and human granulosa cells, a pattern of tropic regulation that differs from other steroidogenic enzyme mRNAs. PMID- 2584225 TI - Crystallization and preliminary X-ray diffraction data of an anti-angiotensin II Fab and of the peptide-Fab complex. AB - mAb-131 is a monoclonal antibody that binds with high affinity (K alpha = 7.4 x 10(9) M-1) to the 8-residue peptide hormone angiotensin II, the major effector of the renin/angiotensin system. mAb-131 is a member of a well characterized idiotypic antibody network since it was raised as an anti-anti-idiotype of an antibody raised against angiotensin II. mAb-131 Fabs prepared with papain contain four major charge isoforms that can be separated by pH gradient elution from an anion-exchange column. Diffraction quality isomorphous crystals of two of the isoforms and of the Fab.peptide complexes have been grown. The crystals diffract to 3.5 A resolution, are tetragonal, space group P4(1) (or P4(3] with cell dimensions a = b = 78.6 A, c = 125.2 A, and have two Fab molecules per asymmetric unit. By using a different buffer, a second crystal form has been grown which diffracts to 3.3 A. It also belongs to space group P4(1) (or P4(3] but has cell dimensions of a = b = 109.6 A and c = 125.2 A. Knowledge of the three-dimensional structure of this Fab and of the peptide.Fab complex will give insight into two problems: 1) the recognition of small peptide hormones (which exist as random coils in solution) with high affinity by proteins, and 2) the nature of conservation of antibody combining sites in idiotypic networks. PMID- 2584226 TI - Reduced biopterin as a cofactor in the generation of nitrogen oxides by murine macrophages. AB - Generation of nitric oxide (NO.), an autacoid with vasorelaxant and cytotoxic properties, requires at least three cytosolic components in mouse macrophages besides L-arginine and NADPH. One or more components appear after induction by immunologic stimuli; two or more are present in both activated and non-activated macrophages. The constitutive factors can be separated on a Mr approximately 30,000 cut-off filter into high Mr fraction (HF) and low Mr fraction (LF) (Stuehr, D. J., Kwon, N. S., Gross, S. S., Thiel, B. A., Levi, R., and Nathan, C. F. (1989) Biochem. Biophys. Res. Commun. 161, 420-426). Herein we characterize the major active component in LF. The active component was dialyzable (Mr less than approximately 1,000), water soluble, and cationic at acidic to neutral pH. Fractionation on a C18 column in an acetonitrile/water gradient yielded one broad peak of activity, most of which corresponded to a fluorophore with the excitation/emission spectra of biopterins. Gas chromatography isolated a species in this peak with the mass spectrum of biopterin. Of 14 pteridines tested, only 7,8-dihydrobiopterin (H2biopterin) or 5,6,7,8-tetrahydrobiopterin (H4biopterin) could replace LF in synergizing with HF and the inducible component(s) to generate NO-2 and NO-3, the accumulating oxidation products of NO.. Half-maximal activity required 20-30 nM reduced biopterins. LFs from three cell lines were active in proportion to their content of biopterins; addition of reduced biopterins restored activity to LF from biopterin-deficient cells. Enhancement of NO-2 generation in the presence of H2biopterin but not H4biopterin was abolished by methotrexate and aminopterin, inhibitors of dihydrofolate reductase. These findings implicate a redox cycle in which the generation of NO. is facilitated by catalytic amounts of H4biopterin. PMID- 2584227 TI - Damage to the bases in DNA induced by hydrogen peroxide and ferric ion chelates. AB - Incubation of a number of ferric ion chelates with H2O2 at pH 7.4 generated a reactive species able to produce chemical modifications of the bases in DNA that are very similar to those produced in DNA by the hypoxanthine/xanthine oxidase system (Aruoma, O.I., Halliwell, B., and Dizdaroglu, M. (1989) J. Biol. Chem. 264, 13024-13028). Products were identified and quantitated by the use of gas chromatography-mass spectrometry with selected-ion monitoring. Compared with other complexes used, ferric ion-nitrilotriacetic acid produced by far the largest amount of the base products. Typical hydroxyl radical scavengers and superoxide dismutase provided significant decreases in the yields of the products. On this basis, it is proposed that ferric ion complexes react with H2O2 to produce hydroxyl radical; this was also shown using the deoxyribose assay. Inhibition of product formation by superoxide dismutase suggests the involvement of superoxide radical in this reaction. It is likely that hydroxyl radical generated by reaction of the ferric ion-nitrilotriacetic acid complex with H2O2 contributes to the carcinogenicity and nephrotoxicity associated with this chelating agent. PMID- 2584228 TI - Regulation of ornithine aminotransferase in retinoblastomas. AB - Ornithine-delta-aminotransferase (OAT) is a nuclear-encoded, mitochondrial enzyme that converts ornithine to glutamate semialdehyde. Although OAT is expressed in most tissues of the rat, liver, kidney, and retina have the highest levels of OAT activity. Studies of OAT regulation in liver and kidney have indicated transcriptional and translational controls for the enzyme in a tissue-specific manner. Little is known about OAT modulation in retinal tissue, although chorio retinal degeneration is the predominant feature in a hereditary disorder of OAT deficiency, gyrate atrophy. To characterize OAT regulation in retinal lines, we studied its synthesis in two retinoblastoma strains, Y79 and RB355. Baseline OAT mRNA levels were similar in the two cell lines, yet Y79 expressed 3-fold more immunoreactive OAT protein and enzyme activity than RB355; this finding suggested the presence of a post-transcriptional mechanism for the regulation of steady state OAT levels. Treatment of the two strains with estradiol or thyroid hormone for 24 h resulted in approximately 5-fold increases in OAT protein and activity. Since similar increases in OAT mRNA levels were observed in both strains after Northern blotting, it is likely that these hormones exert their effects at the transcriptional level. Finally, primer extension analysis revealed two OAT mRNA species in both strains, due to the presence of an additional exon (exon 2) in one of the transcripts. The absence of this exon in other tissues reflects the unique mechanisms which govern OAT in retinoblastomas. PMID- 2584229 TI - Structure of human lysosomal membrane glycoprotein 1. Assignment of disulfide bonds and visualization of its domain arrangement. AB - The amino acid sequence of one of the major lysosomal membrane glycoproteins, lysosome-associated membrane protein 1 (lamp-1), was deduced from its cDNA sequence (Fukuda, M., Viitala, J., Matteson, J., and Carlsson, S. R. (1988) J. Biol. Chem. 263, 18920-18928). This amino acid sequence suggests that lamp-1 contains a hinge-like structure and could form disulfide bridges that are observed in the immunoglobulin superfamily. To test this possibility, we have determined the positions of the disulfide bridges by isolating and sequencing cystine-containing peptides which contain disulfide bridges. The results indicate that disulfide arrangement of lamp-1 is different from that of immunoglobulins. Each molecule contains, in total, four loops formed by disulfide bonds, and each loop contains 36-39 amino acid residues. However, none of the disulfide bonds connects two domains that are separated by a hinge-like structure. The results indicate that the hinge region has no ordered structure, and the relative positions of the two domains can be altered in space. Examination of the ultrastructure of lamp-1 by electron microscopy showed that the hinge-like structure actually functions as a hinge. These results indicate that the lamp-1 molecule represents a novel family of glycoproteins with unique structural properties. PMID- 2584230 TI - The pattern of dihydrofolate reductase expression through the cell cycle in rodent and human cultured cells. AB - We have examined the pattern of dihydrofolate reductase (DHFR) enzyme and mRNA levels in cell cycle stage-specific populations obtained by centrifugal elutriation in Chinese hamster ovary cells and in a derivative line in which the dihydrofolate reductase gene is amplified approximately 50-fold. On a per cell basis, we observed a 2-fold increase in DHFR activity as cells progressed from G1 to G2/M with a concomitant 2-fold increase in the rate of protein synthesis and steady state level of mRNA. Analysis of DHFR mRNA levels in cell cycle stage specific mouse 3T6 and human 143 tk- cells gave a similar pattern. We also demonstrate that simple alterations in growth conditions prior to elutriations can dramatically increase the levels of DHFR mRNA in all cell cycle states, thereby indicating that growth response associated with the DHFR gene functions independent of the cell cycle. We conclude that during periods of exponential growth the increases in dihydrofolate reductase activity, rate of protein synthesis, and steady state levels of mRNA parallel the general increases in cell volume and protein content associated with normal progression through the cell cycle, and therefore DHFR cannot be considered a cell cycle-regulated enzyme. PMID- 2584231 TI - Heme regulates expression of phycobiliprotein photogenes in the unicellular rhodophyte, Cyanidium caldarium. AB - Allophycocyanin and phycocyanin in the red alga (Cyanidium caldarium) are chloroplast-encoded, light-harvesting accessory pigments composed of alpha and beta subunit polypeptides (17-19 kDa) to which 1 or more residues of the heme derived bile pigment chromophore phycocyanobilin are attached by cysteinyl thioether linkages (Offner, G.D., and Troxler, R.F. (1983) J. Biol. Chem. 258, 9931-9940). Western blot experiments utilizing phycobiliprotein antisera revealed that immunoreactive allophycocyanin and phycocyanin apoproteins were absent in cells grown in the dark and present in cells exposed to light. Northern blot experiments using genomic DNA hybridization probes indicated that phycobiliprotein mRNAs were absent in the dark, whereas cells exposed to light contained two allophycocyanin mRNA transcripts, 1.4 and 1.6 kilobases in length, and one phycocyanin mRNA transcript, 3.0 kilobases in length, providing evidence that phycobiliproteins are encoded in photogenes which are only transcriptionally active in the light. Northern and Western analyses demonstrated that cells incubated in the dark with the heme precursor delta-aminolevulinate contained allophycocyanin and phycocyanin mRNAs and apoproteins, indistinguishable in size, number, and quantity from those made in the light. Cells incubated in the dark with delta-aminolevulinate, protoporphyrin IX, or heme, but not biliverdin or phycocyanobilin, synthesized allophycocyanin and phycocyanin alpha and beta apoproteins, suggesting a role for heme in the control phycobiliprotein gene expression. Cells incubated with heme in the dark produced allophycocyanin and phycocyanin mRNA transcripts, but did not produce mRNAs for four other photogenes coding for a P-700 reaction center protein, a 32-kDa herbicide-binding protein, and the large and small subunits of ribulose-bisphosphate carboxylase. These results show, for the first time, that heme is a regulatory factor specifically involved in transcriptional regulation of chloroplast genes for phycobiliproteins. PMID- 2584233 TI - Identification of a 90-kDa polypeptide which associates with adenovirus VA RNAI and is phosphorylated by the double-stranded RNA-dependent protein kinase. AB - Interferon treatment of mammalian cells induces a double-stranded (ds) RNA dependent protein kinase known as DAI. When activated, DAI phosphorylates the alpha-subunit of eukaryotic initiation factor eIF-2, impairing its ability to be recycled and leading to the inhibition of protein synthesis. We have identified a novel DAI substrate in the ribosomal salt wash of rabbit reticulocyte lysates. This substrate is a 90-kDa polypeptide which has been purified to apparent homogeneity. It can be cross-linked by ultraviolet irradiation to adenovirus VA RNAI, a small RNA polymerase III transcript RNA which acts as an inhibitor of DAI. As assayed by a nitrocellulose filter binding assay, the 90-kDa polypeptide is also able to associate with authentic double-stranded RNA, but not single stranded RNA, made in vitro. Thus, this newly identified substrate of DAI appears to have affinity for dsRNA structures and may be involved in dsRNA-regulated processes in the reticulocyte. Polyclonal and monoclonal antibodies directed against the 90-kDa polypeptide co-precipitate DAI, suggesting that these two proteins may exist as a complex. PMID- 2584232 TI - Isolation and characterization of a small intestinal surfactant-like particle containing alkaline phosphatase and other digestive enzymes. AB - Digestive brush-border enzymes in particulate form have been reported in the intestinal lumen in vivo and in medium from organ explants in vitro. It has been suggested that these particles derive from membrane shedding of the apical brush border. This study describes the isolation and characterization of particles derived from the 105,000 x g supernatant fraction of intestinal luminal washings and from light scrapings of the mucosa itself after fat feeding of rats. These fractions were separated in a continuous NaBr gradient, producing a visible band of 1.07-1.08 g/liter density and resulting in a 15-fold enrichment of intestinal alkaline phosphatase in the band fraction. Other brush-border hydrolases were represented in the banded fraction, but at specific activities only 1/5th to 1/36th that of the brush border. The major phospholipid in the fraction was phosphatidylcholine (58 +/- 15%), containing 75% saturated fatty acids. In contrast, the major brush-border phospholipid was phosphatidyl-ethanolamine. These characteristics showed that the particles derived from the lumen and mucosal surface were not identical to fragments of the brush border. Electron microscopy of the banded fraction revealed partially coiled membrane fragments. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blots, some proteins (e.g. surfactant protein B, collagenous protein 4) were found in common between the intestinal particles and rat pulmonary surfactant. These data suggest the production of a particle secreted by rat intestine that differs from brush-border membranes and that shares some morphological and biochemical similarities with pulmonary surfactant. PMID- 2584235 TI - Effect of thyroid hormones on glucokinase gene transcription in rat liver. AB - Thyroid hormones contribute to the regulation of blood sugar by accelerating the turnover of glucose. The mechanism by which thyroid hormones stimulate the rate of glucose utilization in the liver was determined by investigating the effect of different thyroid states on the expression of the glucokinase gene, a key enzyme of glycolysis. In euthyroid rats the mass of glucokinase mRNA increased 8-fold during the first 4 h of refeeding a high carbohydrate diet to 48-h starved rats. In hypothyroid rats under the same conditions only a 2-fold induction was observed. In euthyroid rats a 5-fold increase was obtained 1 h after refeeding, while hypothyroid rats displayed no significant response in glucokinase mRNA within this time. Basal levels of glucokinase mRNA in starved rats were the same observed in eu- and hypothyroid rats. Injection of 3,3',5-triiodothyronine (T3) into hypothyroid rats restored the mRNA levels of refed hypothyroid rats to euthyroid levels within 24 h. However, a 3-fold increase over untreated animals was already observed 3 h after T3 administration. Even subphysiological doses of T3 (0.1 microgram/100 g body weight) led to an significant increase in glucokinase mRNA levels (1.5-fold, p less than 0.05) in hypothyroid rats, whereas higher doses (100 micrograms/100 g body weight) restored the mRNA levels to those of euthyroid controls. Parallel increases in the cytosolic mRNA levels and rate of glucokinase gene transcription were detected when hypo- and euthyroid fasted rats were compared after 4 h of refeeding. It is concluded that thyroid hormones are permissive for the induction of glucokinase during refeeding but have no effect during starvation. They rapidly enhance the rate of gene transcription within the range of their physiologically circulating concentrations. The results suggest a major importance of thyroid hormones in regulating glucose utilization. PMID- 2584234 TI - Photoaffinity labeling of the rabbit reticulocyte guanine nucleotide exchange factor and eukaryotic initiation factor 2 with 8-azidopurine nucleotides. Identification of GTP- and ATP-binding domains. AB - We have covalently modified rabbit reticulocyte polypeptide chain initiation factor 2 (eIF-2) and the guanine nucleotide exchange factor (GEF) with the 8 azido analogs of GTP (8-N3GTP) and ATP (8-N3ATP). Of the five subunits of GEF, the Mr 40,000 polypeptide binds 8-[gamma-32P]N3GTP, and the Mr 55,000 and 65,000 polypeptides bind 8-[gamma-32P]N3ATP. Both 8-N3GTP and 8-N3ATP specifically label the beta-subunit of eIF-2. Covalent binding of 8-azidopurine analogs to the eukaryotic initiation factors is dependent on UV irradiation. Binding of 8-N3GTP and 8-N3ATP is specific for the guanine- and adenine-binding sites on the protein, respectively. GDP and GTP, but not ATP, inhibit the photoinsertion of 8 N3GTP to the protein. Similarly, ATP, but not GTP, inhibits the photoinsertion of 8-N3ATP. The inclusion of NADP+ in the reaction mixtures also interferes with the binding of 8-N3ATP to GEF. Mg2+ inhibits the binding of the 8-azido analogs of GTP and ATP to both eIF-2 and GEF, whereas EDTA stimulates the photoinsertion of these nucleotides. Identical results are obtained when the binding of GTP and ATP to these proteins, in the presence of Mg2+ or EDTA, is estimated by nitrocellulose membranes. In enzymatic assays, 8-N3GTP supports the activity of eIF-2 and GEF, indicating that the interaction of 8-N3GTP is catalytically relevant. PMID- 2584236 TI - High levels of expression of full length human pro-alpha 2(V) collagen cDNA in pro-alpha 2(V)-deficient hamster cells. AB - A full length cDNA encoding human pro-alpha 2(V) collagen was constructed. Partial sequencing of the cDNA and primer extension analysis of mRNA from fibroblasts found that pro-alpha 2(V) mRNA differs from the mRNAs of other fibrillar collagens in the increased length of its 5'-untranslated region. The pro-alpha 2(V) cDNA was placed downstream of the human cytomegalovirus immediate early promoter/regulatory sequences for expression studies in cultured Chinese hamster lung cells. These cells have been shown previously to synthesize large quantities of pro-alpha 1(V) homotrimers as their only collagenous product. Transfection resulted in a number of clonal cell lines that express human alpha 2(V) RNA at levels comparable to, and in some cases greater than, levels found in normal human skin fibroblasts. Pro-alpha 2(V) chains produced in the majority of clonal lines were of sufficient quantity to complex all available endogenous pro alpha 1(V) chains. Chimeric heterotrimers, composed of hamster alpha 1(V) and human alpha 2(V) chains in a 2:1 ratio, were stable to pepsin digestion and were found predominantly associated with the cell layer. Surprisingly, pro-alpha 2(V) chains, in excess to pro-alpha 1(V) chains, were found in the extracellular matrix and, in much greater abundance, in media. These chains were pepsin sensitive, indicating that pro-alpha 2(V) chains can be secreted as nonstable homotrimers or as free chains. PMID- 2584237 TI - The chymotrypsin enhancer core. Specific factor binding and biological activity. AB - A 20-base pair (bp) conserved sequence present in the 5'-flanking regions of genes highly expressed in the exocrine pancreas forms part of the enhancers of the rat amylase 2A, chymotrypsin B, and elastase I genes. Factor(s) that interact with the conserved DNA sequence of the rat chymotrypsin B gene in vitro have been detected in extracts from acinar cells but not in three other cell lines tested. Transfection experiments suggest that the acinar cell factor(s) recognizing this enhancer core sequence are transcriptional activators. Multimers of a 28-bp sequence located by DNase I protection are capable of activating heterologous promoters in acinar cells. In vitro competition binding and methylation interference analyses indicate protein-DNA interactions at two distinct sites 10 base pairs apart on the DNA. This interaction is identical in extracts from cultured acinar cells as well as from whole pancreas tissue. The presence of two contiguous binding motifs on the same face of the DNA suggests that two (multiple) factors cooperate in the transcriptional regulation of this gene. We term these factors CACCTG pan-1 and TTTCCC pan-1. A factor with the binding specificity of the adenovirus major late transcription factor (MLTF) cross-reacts with the factor CACCTG pan-1 in vitro. However, the distribution of this factor in the various cells does not correlate with the activity of the enhancer core element in vivo. Further, conversion of the chymotrypsin sequence into a consensus MLTF site by three-point mutations abolished enhancer activity in acinar cells. Thus, the MLTF-like factor cannot substitute functionally for the factor CACCTG pan-1 and may act as an inhibitor of chymotrypsin enhancer function. PMID- 2584238 TI - Change in the actin-myosin subfragment 1 interaction during actin polymerization. AB - To better characterize the conformational differences of G- and F-actin, we have compared the interaction between G- and F-actin with myosin subfragment 1 (S1) which had part of its F-actin binding site (residues 633-642) blocked by a complementary peptide or "antipeptide" (Chaussepied, P., and Morales, M. F. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7471-7475). Light scattering, sedimentation, and electron microscopy measurements showed that, with the antipeptide covalently attached to the S1 heavy chain, S1 was not capable of inducing G-actin polymerization in the absence of salt. Moreover, the antipeptide carrying S1 did not change the fluorescence polarization of 5-[2-(iodoacetyl) aminoethyl]aminonaphthalene-1-sulfonic acid (1,5-IAEDANS)-labeled G-actin or of 1,5-IAEDANS-labeled actin dimer, compared to the control S1. This result, interpreted as a lack of interaction between G-actin and antipeptide-carrying S1, was confirmed further by the following experiments: in the presence of G-actin, antipeptide.S1 heavy chain was not protected against trypsin and papain proteolysis, and G-actin could not be cross-linked to antipeptide.S1 by 1-ethyl 3[-3-(dimethylamino)propyl]carbodiimide. In contrast, similar experiments showed that antipeptide.S1 was able to interact with nascent F-actin and with F-actin. Thus, blocking the stretch 633-642 of S1 heavy chain by the antipeptide strongly inhibits G-actin-S1 interaction but only slightly alters F-actin-S1 contact. We, therefore postulate that this stretch of skeletal S1 heavy chain is essential for G-actin-S1 interaction and that the G-F transformation generates new S1 binding site(s) on the actin molecule. PMID- 2584239 TI - Identification of sites phosphorylated in bovine cardiac troponin I and troponin T by protein kinase C and comparative substrate activity of synthetic peptides containing the phosphorylation sites. AB - As an extension of our previous reports that cardiac and skeletal muscle troponin I (Tn-I) and troponin T (Tn-T) are excellent substrates for protein kinase C (PKC) (Katoh, N., Wise, B. C., and Kuo, J. F. (1983) Biochem. J. 209, 189-195; Mazzei, G. J., and Kuo, J. F. (1984) Biochem. J. 218, 361-369), we have now determined that PKC phosphorylated serine 43 (and/or serine 45), serine 78, and threonine 144 in the free Tn-I subunit and threonine 190, threonine 199, and threonine 280 in the free Tn-T subunit of bovine cardiac troponin. PKC appeared to phosphorylate the same sites of the subunits present in the form of the troponin complex, as indicated by the similarity in the two-dimensional phosphopeptide maps. Although some of the phosphorylation sites were shared by other classes of protein kinases, PKC exhibited a distinct substrate specificity. It was also noted that phosphorylated serine and threonine residues in Tn-I and Tn-T had neighboring basic amino acid residues separated by 1 or 2 other residues both at the amino and carboxyl termini, in agreement with the conclusion of House et al. (House, C., Wettenhall, R. E. H., and Kemp, B. E. (1987) J. Biol. Chem. 262, 772-777) based upon their studies on other substrate proteins. Several peptides having sequences around the phosphorylating sites have been synthesized. The phosphorylation experiments indicated that these peptides were substrates for PKC, and their relative substrate activity (determined by the ratios of Vmax/Km) compared with other proteins, in descending order, was Tn-I = Tn-I(134-154) greater than Tn-T much greater than histone H1 greater than Tn-I(33-35) approximately Tn-T(268-284) greater than Tn-T(179-198) approximately Tn-T(191 209). It is suggested that PKC phosphorylation of Tn-I and Tn-T could be biologically significant in terms of possible modifications in interactions among the individual contractile protein components as well as the Ca2+ sensitivity and activity of actomyosin ATPase. PMID- 2584240 TI - Purification and characterization of a unique osteoinductive factor from bovine bone. AB - A unique protein that promotes ectopic osteoinduction in the rat has been isolated and characterized. Osteoinductive factor (OIF) was extracted from the organic matrix of bovine bone with 4 M guanidine HCl and purified by gel filtration, ion-exchange chromatography, affinity chromatography, and reversed phase high performance liquid chromatography. OIF is a glycoprotein with an apparent molecular mass of 22-28 kDa based on sodium dodecyl sulfate gel electrophoresis. Enzymatic or chemical deglycosylation of OIF reduces its mass to about 12 kDa with apparent loss of activity. OIF activity in the model used is substantially increased by addition of transforming growth factor (TGF)-beta 1 or TGF-beta 2, suggesting an important role for TGF-beta 1 and -2 in bone regeneration and repair. The N-terminal sequence of OIF has no homology to other reported proteins. PMID- 2584241 TI - The orthopaedic consequences of civil disturbance in Northern Ireland. PMID- 2584242 TI - Congenital dislocation of the hip presenting after the age of three years. A long term review. AB - We reviewed the cases of 38 children with 45 congenitally dislocated hips who presented for primary treatment after the age of three years. Of these, 34 hips were managed by the 'direct approach' of Somerville and Scott (1957); 14 of these required secondary operations for subluxation, often with a poor outcome. Eleven hips were treated by combined pelvic and femoral osteotomy which, in general, gave good results. At a mean follow-up of 16.7 years, 80% of the whole series had a good or excellent clinical result and 51% were good or excellent radiologically. Simultaneous correction both above and below the hip is considered to be the best treatment for the older child with congenital hip dislocation. PMID- 2584243 TI - The skeletal manifestations of congenital syphilis. A review of 197 cases. AB - In a retrospective review of 302 clinically suspected cases of congenital syphilis, bone changes were found in 197. The skeletal manifestations were periostitis (102 cases), osteitis (20), and metaphyseal changes (71). Combinations of more than one lesion were found in 61. Pseudoparalysis was a presenting sign in 34 infants; 12 of these were found to have had pathological fractures and four had dactylitis. Complete radiological healing without residual changes was seen in all 59 cases that were recalled for review. The orthopaedic surgeon should consider the diagnosis of congenital syphilis when destructive lesions of bone are seen in an infant. PMID- 2584244 TI - Morphological changes in the acetabulum in Perthes' disease. AB - Radiographs of 155 Indian children were examined to identify the acetabular changes which occur in Perthes' disease. These changes included osteoporosis of the acetabular roof, irregularity of contour, premature fusion of the triradiate cartilage, hypertrophy of articular cartilage and changes in dimensions. These changes tended to be more marked in older children and when more than half of the femoral epiphysis was involved. Comparison with 25 cases of Perthes' disease from Liverpool showed the same picture. Several of the acetabular changes noted during the active stages were also seen in a series of 24 adult hips after Perthes' disease. Radio-isotope scans of the hips of 27 children with Perthes' disease showed a consistently increased uptake in the acetabulum on the affected side, indicative of a local increase in vascularity and metabolic activity. It was possible to postulate a working model for the pathogenesis of all the acetabular changes. A number of statistical correlations suggest that most of the changes have a bearing on the final outcome. PMID- 2584245 TI - Acetabular fractures in older patients. AB - Retrospective review of 25 patients over 65 years of age with unilateral acetabular fractures managed conservatively showed that seven of the 23 survivors (30%) had an unacceptable functional result. Poor results were associated with: displaced posterior column fractures, osteoporosis, femoral head fracture, delayed diagnosis, inadequate radiographs, inappropriate or too brief traction, and early weight-bearing. In this age group acetabular fractures tend to be low velocity injuries of osteoporotic bone and are not comparable with those in younger patients. PMID- 2584246 TI - Secondary arthroplasty for complications of femoral neck fracture. AB - We report a series of 640 consecutive cervical hip fractures which were followed prospectively for two years after primary internal fixation with two hook-pins. Secondary arthroplasties were performed as salvage procedures in 75 cases and the early outcome of these was studied retrospectively. The mean time in hospital was 25 days for prosthetic replacement, though 60% of the patients had other medical conditions considered as risk factors. Mortality was 5% after six months and 8% after one year. Dislocation was seen in 11% and additional surgery was required in 4%. There was one case of deep infection and one supracondylar femoral fracture. In some cases there was considerable delay between the primary and secondary operation due to lack of awareness of functional deterioration, but although many patients had poor mobility before the secondary operation this was greatly improved within six weeks of the arthroplasty. We conclude that elective secondary hip arthroplasty for failure of fracture fixation is a safe and successful procedure. Once the decision to perform an arthroplasty is taken, this should be done without delay to avoid deterioration of function. PMID- 2584248 TI - Patellofemoral relationships in recurrent patellar dislocation. AB - Magnetic resonance imaging was used to analyse the patellofemoral relationships during the first 30 degrees of knee flexion in women with recurrent patellar dislocation. The patellofemoral joints were imaged both sagittally and axially with the knee flexed 0 degrees, 10 degrees, 20 degrees, and 30 degrees. At the beginning of knee flexion the sulcus angle was greater than in unaffected women, the lateral patellofemoral angle was smaller, the patella displaced further laterally, tilted more laterally and the congruence angle was directed more laterally. At 30 degrees of knee flexion these differences were less marked than at 0 degree to 10 degrees. Logistic regression analysis showed that the sulcus angle at 10 degrees of knee flexion was the most diagnostic feature, indicating that there is an anatomical predisposition to recurrent dislocation and that pathological patellar tracking starts from the beginning of flexion. Traditional sunrise radiographic films taken at 25 degrees to 30 degrees knee flexion clearly miss diagnostically important information. PMID- 2584247 TI - Intertrochanteric osteotomy for non-union of the femoral neck. AB - We report a series of 50 patients under 70 years of age who had an ununited femoral neck fracture treated by a Pauwels abduction osteotomy. At an average follow-up of 7.1 years, seven patients had required prosthetic replacement and 37 others were reviewed in detail. In these patients the Harris hip score averaged 91. Twenty-two hips showed radiographic evidence of avascular femoral head necrosis, but only three of these had been replaced. For active patients with non union of a femoral neck fracture, Pauwels osteotomy provides a high proportion of good results even in the presence of avascular necrosis of the head, providing there has been no collapse. If osteotomy fails, prosthetic replacement is still possible. PMID- 2584249 TI - The total condylar prosthesis. 10- to 12-year results of a cemented knee replacement. AB - Over a two-year period 104 patients had 130 knee arthroplasties performed with the total condylar prosthesis at the Hospital for Special Surgery. At a 10- to 12 year review 58 patients (74 knees) had survived and were available for detailed clinical and radiographic evaluation. Of these, 38 knees (51.3%) were rated as excellent and 27 (36.5%) good. There were three (4.0%) fair and six (8.2%) poor results. Five of the six had had revision operations. The success of this early pattern of prosthesis supports the continued use of methacrylate cement for knee arthroplasties. PMID- 2584250 TI - Survivorship of cemented knee replacements. AB - The survivorship method of analysis has been used to compare the failure rate and overall success of 1,430 cemented primary total knee arthroplasties performed at The Hospital for Special Surgery over a 15-year period. There were 224 total condylar prostheses with a polyethylene tibia, 289 of the posterior stabilised type with an all polyethylene tibia, and 917 posterior stabilised with a metal backed tibial component. There were 12 failures in the total condylar series, giving an average annual failure rate of 0.65% and a 15-year success rate of 90.56%. The posterior stabilised prosthesis with a polyethylene tibia showed an average annual failure rate of 0.27% and a 10-year success rate of 97.34%, and this prosthesis with a metal-backed tibial component gave an annual failure rate of 0.19% and a seven-year success rate of 98.75%. The overall survival rate was not influenced by sex or age, diagnosis or the percentage of ideal body weight. No metal-backed tibial components have yet needed revision for loosening. It seems that infection will be the major cause of failure. PMID- 2584251 TI - Methotrexate diffusion from acrylic cement. Local chemotherapy for bone tumours. AB - We investigated the possible use of acrylic cement containing chemotherapeutic drugs in the treatment of malignant lesions in bone. The diffusion of methotrexate (MTX) from methylpolymethacrylate implants was studied in vitro: polymerisation of the cement did not destroy the drug; liberation began immediately and about 10% was released by 18 hours. Some release continued for as long as six months. In vivo experiments on rats with induced osteosarcoma showed that MTX in cement had both local and general effects which were dependent on the dosage. A series of 17 large dogs with spontaneous osteosarcoma were then treated by local resection and cement containing MTX. General chemotherapeutic effects were detectable from 2 hours to 5 days, survival was increased and local recurrence was reduced, but there were four cases of delayed wound healing. Preliminary studies in human patients confirm the possibility that this method of local chemotherapy could be a useful addition to the treatment of malignant tumours of bone. PMID- 2584252 TI - Intramuscular lipoma of the lower limb. Long-term follow-up after local resection. AB - We report 12 patients with infiltrating muscular lipomas of the lower limbs all treated by wide resection. During follow-up averaging seven years, the tumour recurred in five patients. Our results and those reported by others suggest that, in order to avoid recurrence, this tumour, although benign, should be treated by total excision of the muscle or by compartmental resection. Hormonal imbalance was suspected in 9 of the patients but an oestrogen receptor analysis of the histological samples proved negative. PMID- 2584253 TI - Tendinitis of the pectoralis major insertion with humeral lesions. A report of two cases. AB - Two patients presented with pain in the arm and a radiographic lesion of the upper humerus which warranted surgical exploration and excision biopsy. In both cases the pathology was inflammatory and involved the insertion of pectoralis major. Tendinitis of the pectoralis major with an associated lesion of the humerus has not previously been described. PMID- 2584254 TI - Anterior cruciate ligament replacement. Knee stability and the effects of implants. AB - The anteroposterior stability of cadaveric knees was investigated. There was a wide range of normal laxity; knees were more stable at 90 degrees than at 20 degrees flexion. Anterior cruciate ligament implants with different stiffnesses were inserted; normal stability could always be restored, and the stiffness or extensibility of implants did not affect knee behaviour significantly. The tightness of implants was critical--small tensioning errors caused subluxation, inhibited knee extension and allowed damagingly high implant tensions. It is concluded that the tension of ligament implants could not be adjusted simply with a pre-set instrument; the procedure will remain critically dependent on the judgment of the operating surgeon. PMID- 2584255 TI - Partial tears of the anterior cruciate ligament. Progression to complete ligament deficiency. AB - In a prospective seven-year study, we treated 32 patients with partial ruptures of the anterior cruciate ligament (ACL) verified by arthroscopy. Twelve knees (38%) progressed to complete ACL deficiency with positive pivot shift tests and increased anteroposterior translation on tests with the KT-1000 arthrometer. Patients with partial ACL tears frequently had limitation for strenuous sports, while those developing ACL deficiency had additional functional limitations involving recreational activities. Three factors were statistically significant in predicting which partial tears would develop complete ACL deficiency: the amount of ligament tearing--one-fourth tears infrequently progressed, one-half tears progressed in 50% and three-fourth tears in 86%; a subtle increase in initial anterior translation; and the occurrence of a subsequent re-injury with giving-way. PMID- 2584256 TI - Ligamentotaxis and bone grafting for comminuted fractures of the distal radius. AB - The conventional treatment of comminuted fractures in the distal radius has been unsatisfactory. We therefore made a prospective study using the principle of ligamentotoxis and primary cancellous bone grafting as the uniform method of treatment. Ligamentotaxis was maintained by using an external fixator for three weeks only, after which a carefully monitored programme of rehabilitation was given. We have reviewed 72 consecutive distal radial fractures after a follow-up of 7 to 40 months (average 11 months). Reduction had been maintained during healing and over 80% of patients regained full range of movement in hands, wrists and forearms with strong and pain-free wrist function. Complications were infrequent and gave no real problems. We conclude that distraction, external fixation and bone grafting appears to be an excellent method of treating comminuted fractures of the distal radius. PMID- 2584257 TI - Is the KT1000 knee ligament arthrometer reliable? AB - We set up a trial to test whether the KT1000 arthrometer would give consistent measurements of anteroposterior laxity when used by the same and different examiners on the knees of the same subjects on the same day. The results showed substantial inter- and intra-examiner variation in the measurements both of absolute displacement in single knees and of side-to-side differences between pairs of knees. This casts doubt on the reliability of the instrument when used to compare the results of different techniques for reconstructing injured cruciate ligaments. PMID- 2584258 TI - Deep infection of cemented total hip arthroplasties caused by coagulase-negative staphylococci. AB - We reviewed a series of 91 patients with deep infection of a cemented total hip arthroplasty caused by coagulase-negative staphylococci (C-NS). Of these, 72 were treated by one-stage exchange arthroplasty with a failure rate of 13% due to recurrence of infection. The other 19 patients have started or completed treatment by a two-stage exchange without failure to date. In 27 of the 91 patients multiple strains of C-NS were discovered, many being resistant to previously used antibiotics. The use of gentamicin-containing cement in the primary arthroplasty was significantly associated with the emergence of gentamicin-resistant C-NS in subsequent deep infection. Bacteriological diagnosis of such infections must take into consideration the possibility that multiple strains of the organism are involved. PMID- 2584259 TI - Salvage of failed total knee arthroplasty: the 'beefburger' procedure. PMID- 2584260 TI - A method of interphalangeal joint fusion. PMID- 2584262 TI - Results of surgery for ingrowing toenails. PMID- 2584263 TI - A new physical sign in shoulder arthroscopy. PMID- 2584264 TI - Lobster claw leg. PMID- 2584261 TI - The 'tooth' of the dog that bit him. PMID- 2584266 TI - Prone examination for anterior cruciate ligament insufficiency. PMID- 2584265 TI - A physical sign denoting irreducibility of a dislocated knee. PMID- 2584267 TI - Metatarsophalangeal joint dislocation after local steroid injection. PMID- 2584268 TI - External fixation for fracture-dislocations of the proximal humerus. PMID- 2584269 TI - A technique for reducing diastasis of the symphysis pubis. PMID- 2584270 TI - XIX World Congress of the International Society for Cardiovascular Surgery. September 5-9, 1989, Toronto, Ontario (Canada). Abstracts. PMID- 2584271 TI - Muscarinic cholinergic receptors on the endothelium of human cerebral arteries. AB - To characterize the muscarinic cholinergic receptors on the endothelium of human cerebral arteries, isometric tension measurement and receptor autoradiographic studies were performed. Acetylcholine (ACh) induced dose-dependent relaxation of human cerebral arteries precontracted by 10(-5) M serotonin, with an EC50 of 1.9 +/- 0.6 X 10(-6) M (n = 7). The relaxation was abolished by 10(-5) M hemoglobin. Autoradiography, using the muscarinic antagonist [3H]propylbenzilycholine mustard, demonstrated the high density of muscarinic cholinergic receptors on the endothelial cells of human cerebral arteries, especially on the luminal surface of the endothelium. These findings suggest that ACh-induced relaxation mediated by muscarinic cholinergic receptors on the endothelium has a physiological function in human cerebral arteries. PMID- 2584272 TI - The effects of the GABA agonist muscimol upon blood flow in different vascular territories of the rat cortex. AB - Local cerebral blood flow was measured in five regions of rat cortex immediately following intravenous administration of the gamma-aminobutyric acid (GABA) agonist muscimol. In contrast to recent observations, no increases in blood flow were found at either of the two time points analysed, and the data revealed that decreases in blood flow previously reported 30 min after muscimol treatment were in evidence as early as 30 s. These results are totally consistent with the conclusion that the overall effects of GABA agonists in the intact animal are to reduce blood flow in line with reduced metabolic demand in the neuropil. However, the heterogeneity of the reductions in cortical blood flow found here possibly suggests a biological role for vascular GABA systems in providing a mitigating influence on fluctuating tissue perfusion. PMID- 2584273 TI - Sequential metabolic changes in rat brain following middle cerebral artery occlusion: a 2-deoxyglucose study. AB - The distribution and time course of altered cerebral metabolism following permanent focal ischemia was studied in rat using the 2-deoxyglucose (2DG) technique. Increased 2DG uptake preceded decreased 2DG uptake and infarction in the caudate putamen and cortex. Decreased 2DG uptake without infarction was observed for 72 h in thalamus and for 24 h in hippocampus (areas remote from the ischemic zones). This study supports the concept of cell excitation as a pathophysiologic process in permanent focal ischemia. The time course of increased metabolism may demarcate the time window of opportunity for the previously demonstrated attenuation of stroke size with inhibition of cell excitation by pharmacologic blockade of excitatory amino acid neurotransmission. PMID- 2584274 TI - Glycolysis-induced discordance between glucose metabolic rates measured with radiolabeled fluorodeoxyglucose and glucose. AB - We have developed an autoradiographic method for estimating the oxidative and glycolytic components of local CMRglc (LCMRglc), using sequentially administered [18F]fluorodeoxyglucose (FDG) and [14C]-6-glucose (GLC). FDG-6-phosphate accumulation is proportional to the rate of glucose phosphorylation, which occurs before the divergence of glycolytic (GMg) and oxidative (GMo) glucose metabolism and is therefore related to total cerebral glucose metabolism GMt: GMg + GMo = GMt. With oxidative metabolism, the 14C label of GLC is temporarily retained in Krebs cycle-related substrate pools. We hypothesize that with glycolytic metabolism, however, a significant fraction of the 14C label is lost from the brain via lactate production and efflux from the brain. Thus, cerebral GLC metabolite concentration may be more closely related to GMo than to GMt. If true, the glycolytic metabolic rate will be related to the difference between FDG- and GLC-derived LCMRglc. Thus far, we have studied normal awake rats, rats with limbic activation induced by kainic acid (KA), and rats visually stimulated with 16-Hz flashes. In KA-treated rats, significant discordance between FDG and GLC accumulation, which we attribute to glycolysis, occurred only in activated limbic structures. In visually stimulated rats, significant discordance occurred only in the optic tectum. PMID- 2584275 TI - Effect of the serotonin antagonist ketanserin on the hemodynamic and morphological consequences of thrombotic infarction. AB - The effect of the serotonin (5-hydroxytryptamine, 5-HT) antagonist ketanserin on the remote hemodynamic consequences of thrombotic brain infarction was studied in rats. Treated rats received an injection of 1 mg/kg ketanserin 30 min before and 1 h following photochemically induced cortical infarction. Local CBF (LCBF) was assessed autoradiographically with [14C]iodoantipyrine 4 h following infarction, and chronic infarct size was documented at 5 days. Thrombotic infarction led to significant decreases in LCBF within noninfarcted cortical regions. For example, mean LCBF was decreased to 63, 55, and 65% of control (nontreated normal rats) in ipsilateral frontal, lateral, and auditory cortices, respectively. In rats treated with ketanserin, significant decreases in LCBF were not documented within remote cortical areas compared with controls. In contrast to these hemodynamic effects, morphological analysis of chronic infarct size demonstrated no differences in infarct volume between treated (27 +/- 3 mm3) and nontreated (27 +/- 6 mm3) rats. These data are consistent with the hypothesis that 5-HT is involved in the widespread hemodynamic consequences of experimentally induced thrombotic infarction. Remote hemodynamic consequences of acute infarction can be inhibited without altering final infarct size. PMID- 2584276 TI - Seizure-induced damage to substantia nigra and globus pallidus is accompanied by pronounced intra- and extracellular acidosis. AB - Status epilepticus of greater than 30-min duration in rats gives rise to a conspicuous lesion in the substantia nigra pars reticulata (SNPR) and globus pallidus (GP). The objective of the present study was to explore whether the lesion, which encompasses necrosis of both neurons and glial cells, is related to intra- and extracellular acidosis. Using the flurothyl model previously described to produce seizures, we assessed regional pH values with the autoradiographic 5,5 dimethyl[2-14C]oxazolidine-2,4-dione technique. Regional pH values were assessed in animals with continuous seizures for 20 and 60 min, as well as in those allowed to recover for 30 and 120 min after seizure periods of 20 or 60 min. In additional animals, changes in extracellular fluid pH (pHe) were measured with ion-selective microelectrodes, and extracellular fluid (ECF) volume was calculated from the diffusion profile for electrophoretically administered tetramethylammonium. In structures such as the neocortex and the hippocampus, which show intense metabolic activation during seizures, status epilepticus of 20 and 60-min duration was accompanied by a reduction of the "composite" tissue pH (pHt) of 0.2-0.3 unit. Recovery of pHt was observed upon termination of seizures. In SNPR and in GP, the acidosis was marked to excessive after 20 and 60 min of seizures (delta pHt approximately 0.6 after 60 min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584277 TI - A determination of the regional brain/blood partition coefficient of water using dynamic positron emission tomography. AB - In order to investigate the validity of the single compartment model in measuring CBF with the use of 15O-labeled water (H2 15O), dynamic positron emission tomography (PET) was performed following bolus injection of H2 15O. Careful attention was paid to accuracy in the measurement system (especially for the input function). In the region of the putamen, which includes the smallest mixture of gray and white matters in addition to the smallest contamination of cerebrospinal fluid (CSF) spaces, the partition coefficient obtained was 0.88 +/- 0.06 (ml/g). The discrepancy from the prediction estimated from the brain/blood water content ratio was only 7%. This finding suggests that there is no more complicated model than the usual single compartment one to describe the physiological behaviour of 15O water. On the other hand, in the other cortical regions, the discrepancy was larger (e.g., about 12% for the insular cortex and 26% for the frontal cortex) than in the region of the putamen, and a significant fit-interval dependence was observed in the calculated parameters. These observations suggest a significant effect of tissue heterogeneity and/or contamination with nonperfusable spaces in actual clinical PET data. PMID- 2584278 TI - Direct evidence for acute and massive norepinephrine release in the hippocampus during transient ischemia. AB - Recent studies suggest the norepinephrine (NE) may play a regulatory role in neuronal cell death in the hippocampus after transient ischemia. However, ischemia-induced changes in extracellular NE release have not been demonstrated. In the present study, we utilized the microdialysis technique to measure extracellular NE levels in the hippocampus before, during, and after 20 min of global ischemia induced by two-vessel occlusion combined with systemic hypotension in the rat. Stable basal concentrations of extracellular NE were detected in three consecutive samples collected prior to ischemia (1.86 +/- 1.21 pmol/ml of perfusate mean +/- SEM). During ischemia, NE levels increased to 30.1 +/- 5.5 pmol/ml, representing an 18-fold increase. The levels gradually returned to baseline by 40 min of reperfusion. These results are the first to demonstrate that acute and massive extracellular release of NE occurs in the hippocampus during ischemia and early recirculation. These results support the hypothesis that the activation of the noradrenergic system may play a significant role in modulating the development of ischemic neuronal damage. PMID- 2584279 TI - Decrease of glutamate decarboxylase activity in substantia nigra and caudoputamen following transient hyperglycemic ischemia in the rat. AB - Glutamate decarboxylase (GAD) activity was determined in caudoputamen (CP), substantia nigra (SN), and cerebral cortex (CCX) after 19-22 h of recirculation following 10 min of transient ischemia in hyperglycemic rats, i.e., under the conditions when previously a pronounced nerve cell damage was demonstrated in both CP and SN. The present results demonstrate a decrease of GAD activity in SN by 30% and in CP by 22% and no change in CCX. No statistically significant change in GAD activity could be detected in SN, CP, or CCX 1,4, and 7 days following 10 min of ischemia in normoglycemic animals. The decrease of GAD activity in SN at the time preceding the onset of postischemic seizures suggests that there may be an imbalance between augmented excitatory and decreased inhibitory transmission in SN. We tentatively conclude that this may increase the probability of generalized seizures in the postischemic period following ischemia in hyperglycemic animals. PMID- 2584280 TI - Long-term sampling of cerebral venous blood in conscious rats. AB - The mechanisms of secondary brain damage following cerebral ischemia or CNS trauma are still unknown. A variety of mediators, released by the injured brain, are held to be responsible for delayed neuronal cell damage. No technique is available yet for repeated sampling of cerebral venous blood (CVB) on a long-term basis, which allows to assess the neurobiochemical responses to brain injury chronically in conscious laboratory animals. This is a report on the establishment of a method to sample CVB from the superior sagittal sinus (SSS) for at least 7 days in conscious freely moving rats. The torcular was exposed for implantation of a catheter into the caudal SSS. Patency was preserved by perfusion with a nonsystemic dose of heparin by an Alzet osmotic pump and verified daily by aspirating of 0.5 ml CVB for blood analysis. No neuropathology was seen in histological examination. The rats appeared comfortable and without distress, and the transient weight loss was rapidly regained. The present model provides the opportunity to evaluate acute or chronic neurobiochemical responses to stroke, CNS trauma, or any other typ of brain injury in the conscious rat. PMID- 2584282 TI - Educating the educator--implications for psychiatric pharmacy. PMID- 2584281 TI - Why the deoxyglucose method has proven so useful in cerebral activation studies: the unappreciated prevalence of stimulation-induced glycolysis. PMID- 2584283 TI - A 10-year review of the Teaching Hospital-Based National Drug and Toxicology Information Service in Zimbabwe. AB - The drug and toxicology information service (DaTIS), at the Department of Pharmacy, University of Zimbabwe Medical School, was set up in 1979. The service is mainly delivered to health professionals and to a lesser extent to the community. The DaTIS is designed to help solve complex clinical questions. Most of the requests are made by telephone. Urgent questions may be initially answered by telephone, or a phone call can be returned after in-depth documentation. A complete answer with references may be written and sent to the enquirer. Written non-urgent questions may be sent a few days to a few weeks later. This report is based on a systematic review of records compiled over the period between January 1983 and July 1988. Of the 1,000 requests received and recorded during the period under consideration, approximately 750 (75%) were on drug information and 250 (25%) were on poisoning or toxicological information. The most common causes of poisonings were due to organophosphate pesticides and fertilizers, Elephant's Ear, Amanita Phalloides mushroom, medicines affecting the central nervous system, e.g. tranquilizers, psychotropics, and chemicals, especially those used for hair relaxing. Only the first three causes of poisoning are discussed in detail. Most of the queries relating to poisoning, especially those received during the night, were not recorded. These results confirm the need for an adequate number of qualified and committed manpower to share the work-load in DaTIS as well as in teaching, research and in the continuous health education of the community. The results obtained by DaTIS and a recent survey (14) indicate that Zimbabwe has a big poisoning problem, especially with regard to pesticides and treatments recommended by the traditional healer. Education and information dissemination to health professionals, workers and the general public on the toxic agents concerned are vital and, although steps have been taken in this direction, much still remains to be done. Moreover, the report confirms the importance of the service to health professionals and the community in the country and the SADCC (Southern African Development Conference Committee) region as a whole. PMID- 2584284 TI - Kinetics of bacterial growth in simple intravenous solutions and admixtures. AB - The growth of bacteria in intravenous solutions and admixtures has been studied under stationary conditions of incubation. All the solutions were inoculated with 100 organisms/ml, incubated at room temperature (27 degrees C) or (37 degrees C), with samples withdrawn at specified time intervals, and plated in quadruplicates. The simple intravenous (i.v.) solutions did not support significant growth (P greater than 0.05) of any of the micro-organisms. Growth in i.v. solutions containing 1% blood was very significant (P greater than 0.05), as demonstrated by the high apparent growth rate constants (K). The ratio of K for beta-lactamase producing bacteria (beta-lac+) over that for non-beta-lactamase producing bacteria (beta-lac-) was significant (P less than 0.05) at 37 degrees C compared to that at 27 degrees C. The higher K values for B. cereus in benzylpenicillin and cefuroxime solutions, respectively, compared to those in antibiotic-free solutions, may be attributable to hydrolysis of the drugs, while the low K values for B. subtilis in the same solutions may be attributed to the inhibitory effects of the drugs. In conclusion, minute quantities of blood in i.v. solution tend to cause bacteria to multiply rapidly. The presence of beta-lactamase producing species might, in addition, hydrolyse susceptible beta-lactam antibiotics which are common additives to i.v. fluids. PMID- 2584285 TI - The influence of nifedipine and diltiazem on serum theophylline concentration time profiles. AB - Chronic dosing studies in normal volunteers have shown that both nifedipine and diltiazem exert a small effect on serum theophylline concentrations, which tend to be higher during concurrent nifedipine therapy. The differences were not significant but may be of clinical interest as theophylline causes adverse effects at higher plasma concentrations. PMID- 2584286 TI - [Axillo-femoral bypass. Long-term results]. AB - 182 patients underwent axillo-femoral bypass between April 1974 and December 1981 (29 women and 153 men). Mean survival was 43 months. The mean age was 68 years (range: 40-90). 10.9% of patients were Leriche stage II, stages III and IV accounted for 69.7% of cases. All presented a high surgical risk with cardiac disease present in 43.4% and severe respiratory failure in 36.8%. Depending on the year studied, this procedure represented 10 to 15% of the aorto-iliac revascularisations carried out. Mortality was low (5 cases = 2.7%). Early complications (15%) included 11 cases (6%) of early thrombosis requiring reintervention, and late complications included 48 cardiac problems (26.3%). Analysis of the results in the long term was carried out according to an actuarial method over a period of 10 years. The secondary permeability rate was 86.4% at 5 years and 68.8% at 10 years with a 30% secondary thrombectomy rate (25% long term). Limb conservation at 5 and 10 years was respectively 91.1% and 82.7% while for the same periods survival was 46.7% and 19.7%, confirming the grave condition of the patients. We can conclude that axillo-femoral bypass remains a simple and reliable method with good long term results. When extra anatomical revascularisation seems indicated, it is particularly suitable for subjects in very poor general health. PMID- 2584287 TI - [Cystic duplications of the esophagus in adults. Report of 2 cases]. AB - Oesophageal duplications account for less than 10% of the benign tumors of the oesophagus and for 20% of intestinal duplications. They are most often seen during childhood. In the adult it is more often the non communicating cystic forms, which are prone to complication, which have been reported. Cervical localization is rare and up to now no case has been described in the adult. We report here an asymptomatic case. Our second patient, who had a duplication in the mediastinal region, presented with a cough and dysphagia which completely regressed after excision. PMID- 2584288 TI - [Impingement syndrome of the shoulder. 50 cases treated by Neer's anterior acromioplasty]. AB - The authors present the preliminary results of 50 cases of impingement syndrome treated surgically using an operative technique which at least included an anterior Neer acromioplasty. Surgery was performed after a period of progression ranging from several months to several years. These included 2 Neer stage 1 (4%), 29 stage II (58%) and 19 stage III (38%). In all cases an anterior Neer acromioplasty was carried out. In 18 cases, an additional procedure was also performed (resection of the acromial extremity of the clavicle, suture of a rotator cuff rupture, resection reinsertion of the long head of biceps and an Apoil and Augereau deltoid flap procedure). Results could be assessed in 48 cases (2 cases lost to follow up). They demonstrated 31 very good (i.e. 64.5%), 12 good results (i.e. 25%) and 5 poor results (i.e. 10.5%). PMID- 2584290 TI - [A rare cause of obstruction: hernia through the hiatus of Winslow. Apropos of 3 cases]. AB - Exceptional pathology whose preoperative diagnosis is based upon clinical and radiological signs; the herniation through the foramen of Winslow is a variety of internal herniation. About three recent cases observed in the service, it seemed interesting to see, reviewing literature, what are the diagnostic characters and therapeutic modalities knowing difficulties because of a quasi exclusive vascular collect. PMID- 2584289 TI - [Mechanical obstruction of the duodenum after surgery of the abdominal aorta]. AB - The authors report two cases of duodenal obstruction occurring after insertion of an aorto-iliac prosthesis. This form of mechanical obstruction is much rare than the other forms of post-operative mechanical intestinal obstruction. While the need for surgery is often evident, precise diagnosis before the procedure is seldom obtained. CT scan appears to be the investigation of choice. This complication could be prevented by an epiploplasty covering the graft implant region. PMID- 2584292 TI - [What is new in the diagnosis of appendicitis? Borborygmi in the cecal region]. AB - The author analysed a homogeneous prospective series of 200 appendectomies. He studied the reliability of various elements in the diagnosis of appendicitis, including a new physical sign: borborygmi in the cecal region, an objective element on clinical examination which was present in 65% of cases. Its association with pain on rectal examination allowed a diagnostic certainty of 98% to be obtained. PMID- 2584291 TI - [Fatal appendectomy caused by postoperative gas gangrene of the abdominal wall. 2 cases]. AB - The authors report two cases of post-appendicectomy gas gangrene with a fatal outcome. Based on the study of these two cases they analyse the incidence, mechanism and prognosis of this serious post-operative complication. They stress the prophylactic measures necessary for prevention. PMID- 2584293 TI - Studies on steroids. CCXXXXV. Determination of 5 beta-cholestanoic acids in human urine by gas chromatography-mass spectrometry with negative ion chemical ionization detection. AB - A method for the determination of 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid (DHCA) and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) in human urine by gas chromatography (GC) in combination with negative ion chemical ionization (NICI) mass spectrometry is described. Unconjugated, glycine- and taurine-conjugated DHCA and THCA labelled with 18O and 2H were used as internal standards. 5 beta-Cholestanoic acids in urine were extracted with a Sep Pak C18 cartridge, separated into the unconjugated, glycine- and taurine conjugated fractions by ion-exchange chromatography on piperidinohydroxypropyl Sephadex LH-20 and, following alkaline hydrolysis of conjugated forms, derivatization into the pentafluorobenzyl ester-dimethylethylsilyl ethers. Subsequent resolution of each fraction into DHCA and THCA was attained by GC on a cross-linked 5% phenylmethylsilicone fused-silica capillary column where 5 beta cholestanoic acids were monitored with a characteristic carboxylate anion [M-181] in the NICI mode using isobutane as a reagent gas. The method was applied to separation and determination of 5 beta-cholestanoic acids in urine from a patient with Zellweger syndrome and from healthy volunteers. PMID- 2584294 TI - Gas chromatographic-mass spectral studies after methylation of metabolites produced by some anaerobic bacteria in spent media. AB - The gas chromatographic analysis of metabolites such as volatile fatty acids (VFAs) and non-volatile fatty acids (NVFAs) for identification of anaerobic bacteria is now widely performed. Cultures of anaerobes tested for NVFAs as methyl esters were found to contain several unidentified compounds not previously detected and/or reported with methylation procedures. Gas chromatographic-mass spectrometric studies demonstrated that these compounds correspond to the methyl esters of both saturated and unsaturated short-chain fatty acids, and also of 2 hydroxy and 2-oxo acids. The distribution of these acids among different species of anaerobes was determined and their amounts were measured. The effects of supplementing the culture medium with either glucose or amino acids on the production of these acids are described. The use of very polar stationary phases is suggested for a better separation of all NVFAs. PMID- 2584295 TI - Determination of urinary 3-methoxy-4-hydroxyphenylethylene glycol and its conjugates by high-performance liquid chromatography with electrochemical and ultraviolet absorbance detection. AB - A simple method for the determination in urine of the norepinephrine metabolite 3 methoxy-4-hydroxyphenylethylene glycol (MHPG) and its conjugated derivatives is described. After an extraction procedure similar to that described by Gaertner and Wiatr [J. Clin. Chem. Clin. Biochem., 18 (1980) 579] isocratic high performance liquid chromatographic separation is performed. MHPG can be detected by either electrochemical or absorbance detection (278 nm). Free MHPG is determined directly, whereas MHPG sulphate and MHPG glucuronide are determined after enzymic hydrolysis. Since total MHPG, which represents the sum of these substances, is determined separately, a comparison of the results allows the effectiveness of the hydrolysis of the MHPG derivatives for each urine sample to be determined. For quantitation, the method of adding standard amounts of MHPG is used. PMID- 2584296 TI - Routine measurement of plasma catecholamines in clinical pharmacology by high performance liquid chromatography with electrochemical detection. AB - A method for the simultaneous determination of epinephrine, norepinephrine and dopamine in human plasma is described, which combines the advantages of liquid liquid extraction sample preparation, high-performance liquid chromatography on weak cation-exchange stationary phases and dual-electrode coulometric detection. The limits of quantification are less than 5 pg/ml (at a signal-to-noise ratio greater than 5) for each analyte. The influence of various experimental parameters (e.g., composition of the mobile phase, pretreatment of the assay buffer, components of the re-extraction system) on the performance of the assay is reported in detail. A number of applications are presented, which demonstrate the quality of the data obtained in terms of sensitivity, reproducibility and significance. PMID- 2584297 TI - Determination of isoniazid methanesulphonate and its metabolites in rabbit blood by high-performance liquid chromatography. AB - A rapid and sensitive high-performance liquid chromatographic method is described for simultaneous determination of isoniazid methanesulphonate (IHMS) and its metabolites, such as isoniazid (INH) and acetylisoniazid (AcINH) in rabbit blood. According to stability studies, IHMS was most stable at pH 3-5. After acidifying the blood to pH 5.0, a suitable amount of acetonitrile was added to the supernatant for extraction and niacinamide served as an internal standard. After evaporation, the residue was reconstituted with phosphate buffer and aliquots of this solution were separated on a reversed-phase phenyl column by a mobile phase consisting of 0.25 mM tetrabutylammonium phosphate as a paired-ion reagent. UV detection was performed at 280 nm. Under these conditions, the between-run coefficients of variation of IHMS, INH and AcINH from 1 to 25 microns/ml were 4.7 +/- 2.5, 5.4 +/- 1.0 and 5.1 +/- 3.1%, respectively. Hence this sensitive, reproducible and accurate method was suitable for pharmacokinetic studies of IHMS. PMID- 2584298 TI - Direct determination of codeine-6-glucuronide in plasma and urine using solid phase extraction and high-performance liquid chromatography with fluorescence detection. AB - A sensitive and selective method was developed for the direct determination of codeine-6-glucuronide in plasma and urine using high-performance liquid chromatography (HPLC) with fluorescence detection. Codeine-6-glucuronide was synthesised and its purity estimated using acid and enzyme hydrolysis. The hydrolysis of codeine-6-glucuronide by beta-glucuronidase was incomplete and urine reduced the extent of hydrolysis. Codeine-6-glucuronide was recovered from plasma using a solid-phase extraction column and separated on a reversed-phase C18 HPLC column. The assay showed good reproducibility and accuracy (within 10%), and standard curves were linear between 32 and 1600 ng/ml in plasma and between 0.32 and 160 micrograms/ml in urine. The assay has been applied to the study of the pharmacokinetics and metabolism of codeine in patients. PMID- 2584299 TI - High-performance liquid chromatographic method for the simultaneous determination of enrofloxacin and its primary metabolite ciprofloxacin in canine serum and prostatic tissue. AB - A simple and sensitive high-performance liquid chromatographic method was developed for the determination of enrofloxacin and ciprofloxacin in canine serum and prostatic tissue. Sample preparation consisted of mixing canine serum with a 1:1 dilution of acetonitrile and 0.1 M sodium hydroxide followed by ultrafiltration through a 10,000 molecular mass cut-off filter. Prostatic tissue was sonicated with the same solution prior to ultrafiltration. Separation of these two quinolones in the ultrafiltrate was accomplished by ion-paired liquid chromatography using a reversed-phase analytical column eluted with an acetonitrile-methanol-water solution. Enrofloxacin and ciprofloxacin were detected by a photometric ultraviolet-visible detector set at 278.6 nm and confirmed by a photodiode array detector operating from 230 to 360 nm. The limits of detection for enrofloxacin and ciprofloxacin were 4 and 2 ng/ml, respectively. PMID- 2584300 TI - Presence of tetrahydroisoquinoline, a parkinsonism-related compound, in foods. PMID- 2584302 TI - Separation of C-17 fatty acid esters of 17 beta-estradiol by reversed-phase high performance liquid chromatography. PMID- 2584301 TI - Separation of alkylacyl and diacyl glycerophospholipids and their molecular species as naphthylurethanes by high-performance liquid chromatography. PMID- 2584303 TI - Chromatographic determination of percutaneous absorption of topical non radiolabelled prednisolone in vivo, and preliminary application to transdermal pharmacokinetics. PMID- 2584304 TI - Simultaneous determination of L-homoserine and L-homoserine lactone by reversed phase liquid chromatography in acid hydrolysates of proteins after cyanogen bromide treatment. PMID- 2584305 TI - Simple method of measurement of orotic acid and orotidine in urine. PMID- 2584306 TI - Mass spectrometric determination of tetrabenazine using a stable isotope-labeled analogue as an internal standard. PMID- 2584307 TI - Measurement of zipeprol in rat plasma by gas chromatography with nitrogen phosphorus detection. PMID- 2584308 TI - Rapid high-performance liquid chromatographic method for the quantification of mexiletine and its metabolites in serum. PMID- 2584309 TI - Simultaneous measurement of prednisone, prednisolone and 6 beta hydroxyprednisolone in urine by high-performance liquid chromatography using dexamethasone as the internal standard. PMID- 2584310 TI - Capillary gas chromatographic-mass spectrometric determination of stable isotopically labelled and unlabelled theophylline in serum and urine and of 1,3 dimethyluric acid in urine. AB - A capillary gas chromatographic-mass spectrometric method for the determination of [13C,15N2]theophylline and unlabelled theophylline (TP) and of 1,3 dimethyluric acid (1,3-DMU), a major metabolite of TP, is described. TP and the metabolite were extracted separately from serum or urine, purified by high performance liquid chromatography and converted into alkyl derivatives (monoethyl TP and dibutyl-1,3-DMU). The internal standards used for the respective determinations were [2H6]TP and [2H6]1,3-DMU. Detection was performed by monitoring the molecular ions of the alkyl derivatives. The method needed no complex corrections for contributions and provides good accuracy and precision. PMID- 2584311 TI - Sulfonium salts as derivatizing agents. 2. Determination of theophylline in plasma by automated gas chromatography. AB - An automated gas chromatographic method for determination of theophylline in plasma is described. A novel feature of this assay is the use of triethylsulfonium hydroxide as an on-column alkylating agent. A simple extraction procedure together with automated sample injection and data processing has facilitated processing of large numbers of samples generated in pharmacokinetic studies. The between-run coefficient of variation was 2.2% at 5 micrograms/ml (n = 5) and 3.9% at 15 micrograms/ml (n = 6). Within-run coefficient of variation was 2.4% at 5 micrograms/ml (n = 9) and 3.3% at 15 micrograms/ml (n = 6). Accuracy was 105% at a concentration of 5 micrograms/ml and 102% at 15 micrograms/ml. PMID- 2584312 TI - Comparison between two methods for the determination of the total and free (R)- and (S)-disopyramide in plasma using an alpha 1-acid glycoprotein column. AB - Two different high-performance liquid chromatographic systems for the determination of the total and free (R)- and (S)-disopyramide (DP) in plasma and urine were compared. In method I a Nucleosil C8 column was coupled in series with an alpha 1-acid glycoprotein column. Method II consisted of two systems; a LiChrosorb Si 60 column was used for the determination of the racemic drug concentration and the R/S ratio was determined on an alpha 1-acid glycoprotein column. The recovery of (R)- and (S)-DP from plasma was greater than 97% in both methods. The precisions of the (R)- and (S)-DP determinations in plasma are high with both methods. The relative standard deviations for the determination of the free concentration do not exceed 6.5% at 1.59 micrograms/ml racemic DP. Method II is preferred as it can also be used to determine the concentration of (R)- and (S)-monodesisopropyramide. It is also easier to avoid disturbances from endogenous compounds in plasma samples with method II than with method I. It was observed that DP was incorporated into urine sediment during storage. A simple ultrasonic treatment of the urine samples was demonstrated to release DP from the sediment. PMID- 2584313 TI - Determination of (R)- and (S)-propranolol in plasma by high-performance liquid chromatography using N-benzoxycarbonylglycyl-L-proline as chiral selector in the mobile phase. AB - A normal-phase chromatographic method for the determination of (R)- and (S) propranolol in plasma is described. The chiral separation is performed by adding an optically active complexing agent, N-benzoxycarbonylglycyl-L-proline, to the mobile phase (dichloromethane). The solid phase is LiChrosorb DIOL. After adjustment of the pH of the plasma, the propranolol enantiomers are extracted into hexane-dichloromethane-n-butanol (72:18:10). The organic phase is evaporated and the residue dissolved in the mobile phase before injection on to the column. Quantifications are performed by using internal standardization, giving a precision of better than 2% (coefficient of variation). The method employs 1-ml plasma samples and has linear calibration graphs (r = 0.999) over the concentration range studied, 9.2-288 nmol/l. injections of sample solutions with a composition different from that of the mobile phase gave system peaks that might affect the shape of the solute peaks. Several possibilities for avoiding these disturbing system peaks in the chromatogram by changing the mobile phase composition are discussed. PMID- 2584315 TI - Quantification of L-3-(3-hydroxy-4-pivaloyloxyphenyl)alanine (NB-355) by high performance liquid chromatography using o-phthalaldehyde/N-acetyl-L-cysteine derivatization. AB - A new and rapid high-performance liquid chromatographic assay has been developed for the determination of L-3-(3-hydroxy-4-pivaloyloxyphenyl)alanine (NB-355,I), a novel prodrug of L-DOPA. The method involves precolumn derivatization of the drug in biological samples with o-phthalaldehyde (OPA) and N-acetyl-L-cysteine (NAC) in a triethanolamine buffer (pH 8.0), giving a fluorescent compound that is stable for 2 h at 4 degrees C. Use of an internal standard improved the assay in accuracy and reliability. A programmable injector allowed automatic derivatization of large numbers of samples. Chromatographic separation was performed on a reversed-phase column (Capcell Pak C18) in which the silica gel was coated with silicone polymer. The peaks corresponding to compound I and the internal standard were eluted within 16 min with a mobile phase of acetonitrile phosphate buffer (pH 7.1). The reliable limit of quantification was 0.5 pmol per injection (0.05 micrograms equivalents of L-DOPA per ml in plasma). The method was successfully applied for the measurements of dog plasma concentrations after oral dosing of compound I. PMID- 2584316 TI - High-performance liquid chromatographic method for the quantification of several diamidine compounds with potential chemotherapeutic value. AB - A high-performance liquid chromatographic method has been developed for the detection and quantification of pentamidine and pentamidine analogues of chemotherapeutic value in order to measure their concentration in physiological fluids. The compounds were extracted from urine over octadecyl solid-phase extraction columns, followed by chromatographic separation with an octadecyl reversed-phase column. For the mobile phase, a gradient of 31.5-37.5% acetonitrile in water, with sodium heptanesulfonate and tetramethylammonium chloride as ion modifiers, was used. This method was used to reliably detect levels as low as 341 ng/ml without concentration of the compounds during the solid-phase extraction. The assay was used to determine the effectiveness of several solid-phase extraction columns for isolating the compounds of interest and to quantify the amount of pentamidine and its analogues contained in the urine of dosed rats. PMID- 2584317 TI - Comparison of high-performance liquid chromatography and the Abbott fluorescent polarization radioimmunoassay in the measurement of methotrexate. AB - A modified high-performance liquid chromatographic (HPLC) technique for the assay of methotrexate is described and compared to the Abbott Fluorescence Polarization Radioimmunoassay. The reproducibility (coefficient of variation) at low concentrations was similar for the two assays: 8.1 and 8.5% for the Abbott and HPLC assay, respectively. The limit of detection of the two assays was also similar at 0.01 microM. The correlation coefficient for Abbott versus HPLC was 0.9833 with a gradient of 0.9545. Aspirin was the only drug that interfered with HPLC. Methotrexate's metabolite 7-hydroxymethotrexate did not interfere with the Abbott assay. Plasma half-lives were similar to oncology patients in the two rheumatological patients studied. The 7-hydroxymethotrexate half-life was 15 h. PMID- 2584314 TI - High-performance liquid chromatographic analysis of the enantiomers of flurbiprofen and its metabolites in plasma and urine. AB - Reversed-phase high-performance liquid chromatographic methods have been developed to quantitate the R- and S-enantiomers of flurbiprofen and its major metabolites, 4'-hydroxyflurbiprofen, 3'-hydroxy-4'-methoxyflurbiprofen, and 3',4' dihydroxyflurbiprofen. The compounds are extracted from plasma or urine and derivatized with S-(alpha)-methylbenzylamine to form diastereomeric amides which are readily separated on a C18 column. Fluorescence detection resulted in detection limits that readily allowed us to characterize the disposition of R- and S-flurbiprofen and its major metabolites in man following therapeutic doses. PMID- 2584318 TI - Determination of manidipine and its pyridine metabolite in human serum by high performance liquid chromatography with ultraviolet detection and column switching. AB - A highly sensitive and selective high-performance liquid chromatographic method using column switching is described for the determination of the dihydropyridine calcium antagonist manidipine (I),2-[4-(diphenylmethyl)-1-piperazinyl]ethyl methyl (+/- )-1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5- pyridinedicarboxylate, and its pyridine metabolite (II), 2-[4-(diphenylmethyl)-1 piperazinyl]ethyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-3,5 pyridinedicarboxylate, in human serum. The method is based on the combination of the column-switching technique and ion-pair chromatography. In the first ODS column, I and II are preseparated from endogenous substances in serum with a mobile phase containing sodium nonane sulphonate as an ion-pair reagent. After column switching, in the second ODS column, the heart-cut fraction containing I and II is further separated from the co-eluted substances through the first column with a mobile phase containing no ion-pair reagent. By using microbore columns with a diameter of 2.1 mm, the sensitivity is almost double that given by conventional bore columns with a diameter of 4.6 mm. The method offers high sensitivity and selectivity with short-wavelength ultraviolet detection at 230 nm. The detection limits of both I and II are 0.1 ng/ml using 1 ml of serum. The method is suitable for the pharmacokinetic study of I.2HCl after oral administration to man. PMID- 2584319 TI - Simultaneous determination of pyrimethamine and mefloquine in human plasma by high-performance liquid chromatography with ultraviolet detection. AB - A rapid, sensitive and selective method was developed for the simultaneous determination of pyrimethamine and mefloquine, two of the active ingredients of Fansimef, in human plasma. The procedure involved extraction of the compounds and the internal standard nitrazepam from basified plasma with dichloromethane and chromatography on a C18 column (microBondapak, 300 X 3.9 mm I.D.) with acetonitrile-phosphate buffer as the mobile phase and UV detection at 222 nm. The limit of quantification was 10 ng/ml for both substances, using a 1-ml plasma specimen. The mean inter-assay precision was 2.8% for pyrimethamine and 4.7% for mefloquine up to 800 ng/ml. The practicability of the method was demonstrated by the analysis of more than 1200 plasma samples from several pharmacokinetic studies involving single-dose administration of Fansimef to both patients and volunteers. PMID- 2584321 TI - Analytical studies on beta-lactam antibiotics. III. Automated high-performance liquid chromatographic method for the determination of the orally active antibiotic ceftibuten in human plasma and urine. AB - A fully automated high-performance liquid chromatographic method was established for the determination of the oral cephalosporin antibiotic ceftibuten. The procedure for plasma assay involves on-line sample clean-up with a precolumn of BSA-ODS (ODS coated with bovine serum albumin) and subsequent determination of the drug with a reversed-phase C18 column using a column-switching technique. The precolumn effectively removed protein components and hydrophilic substances from plasma, with ceftibuten and its metabolite, the trans-isomer of ceftibuten, being retained using an ion-pairing reagent, tetra-n-butylammonium bromide, in the mobile phase. In urine assay, an ODS precolumn was used in place of the BSA-ODS column. The urine sample, after 10-fold dilution, was analysed in a similar manner to that used in the plasma assay. A large proportion of hydrophilic substances was eliminated by the on-line clean-up and the residual interfering substances introduced into the analytical column were separated from ceftibuten and its metabolite using the ion-pairing reagent. This method permits the determination of 0.1-20 micrograms/ml of ceftibuten and its metabolite in human plasma and 1-200 micrograms/ml of both compounds in urine. The advantages of the method are easy performance without manual sample preparation, saving of plasma (50 microliters) and high sensitivity. The method was applied to pharmacokinetic studies of ceftibuten after oral administration to healthy subjects. PMID- 2584322 TI - Simultaneous determination of flurazepam and its metabolites in human plasma by high-performance liquid chromatography. AB - A sensitive isocratic high-performance liquid chromatographic method is described, which allows the precise and accurate quantification of flurazepam and four metabolites with a single determination. A pharmacokinetic study was performed on nine volunteers and the main pharmacokinetic data are reported. The method was used to demonstrate that monodesethylflurazepam and didesethylflurazepam are major metabolites in men. One more unidentified flurazepam metabolite was detected. PMID- 2584324 TI - Determination of phosphoethanolamine in animal tissues by gas chromatography with flame photometric detection. PMID- 2584320 TI - Long-chain fatty acids and alcohols from gerbil meibomian lipids. AB - Capillary gas chromatography-mass spectrometry was used to identify constituent fatty acids, alcohols and steroids from gerbil meibomian glands. Over 80 compounds representing about 90% of the total fraction were identified. The major steroid was cholesterol accompanied by a lower concentration of 3 beta-hydroxy-5 alpha-cholestane. Fatty acids with chain lengths from 12 to 27 carbon atoms were present; they had predominantly straight, iso or anteiso chains with major concentrations in the C15-C18 and C25-C27 regions. Unsaturated acids had mainly 16 and 18 carbon atoms. The fatty alcohols were mainly branched-chain with the majority of compounds having chain lengths of 25-27 carbon atoms. Several alcohols, both branched and unsaturated, were found with chains of up to 33 carbon atoms long. The profile was similar to that found earlier in other species, but with lower concentrations of mono-unsaturated compounds than were found in rats and humans. Di-hydroxy compounds, on the other hand, tended to be more abundant although still of low relative concentration. PMID- 2584323 TI - Analysis of fatty acids in equine cerebrospinal fluid using gas chromatography with electron-capture detection. PMID- 2584326 TI - Measurement of urinary free catecholamines using high-performance liquid chromatography with electrochemical detection. PMID- 2584327 TI - Purification of the isolated beta-chain of adult human haemoglobin from its post translational modification. PMID- 2584325 TI - Rapid, quantitative method for the isolation and purification of gangliosides by LIPSEP gel chromatography. PMID- 2584329 TI - Characterization of the antidiarrhoeal loperamide by gas chromatography-mass spectrometry and application of the Hofmann degradation and Cope elimination reaction. PMID- 2584330 TI - Gas chromatographic and mass spectrometric analysis of articaine in urine. PMID- 2584328 TI - Determination of meprobamate in serum by alkaline hydrolysis, trimethylsilyl derivatization and detection by gas chromatography-mass spectrometry. PMID- 2584331 TI - Rapid high-performance liquid chromatographic method for the determination of oxolinic acid in fish serum employing solid-phase extraction. PMID- 2584332 TI - Determination of velnacrine in plasma and urine by high-performance liquid chromatography. PMID- 2584333 TI - Determination of mizoribine in plasma using ion-pair high-performance liquid chromatography. PMID- 2584334 TI - Determination of crotamiton in plasma and urine by high-performance liquid chromatography. PMID- 2584335 TI - High-performance liquid chromatographic assay for timolol in the aqueous humor of the eye. PMID- 2584337 TI - Stereoselective determination of plasma pindolol in endotoxin-pretreated rats by high-performance liquid chromatography. PMID- 2584336 TI - Reversed-phase high-performance liquid chromatographic assay for the determination of mezlocillin in human and rat biological samples. PMID- 2584338 TI - High-performance liquid chromatography of chlorambucil prodrugs structurally related to lipids in rat plasma. PMID- 2584339 TI - Determination of tacrine and its 1-hydroxy metabolite in plasma using column liquid chromatography with ultraviolet detection. PMID- 2584340 TI - Sensitive high-performance liquid chromatographic assay for albendazole and its main metabolite albendazole sulphoxide in plasma and cerebrospinal fluid. PMID- 2584341 TI - Column liquid chromatography of calcium channel blockers. PMID- 2584342 TI - Gas chromatographic-mass spectrometric analysis of threo-methylphenidate enantiomers in plasma. PMID- 2584343 TI - Modified high-performance liquid chromatographic assay for antipyrine and its three major metabolites in urine. PMID- 2584344 TI - Separation and quantitation of free cholesterol and cholesteryl esters in a macrophage cell line by high-performance liquid chromatography. AB - A method for the direct high-performance liquid chromatographic (HPLC) determination of free cholesterol and the individual cholesteryl esters in cell culture experiments is described. The murine macrophage-like J774 cell line was loaded with cholesterol by incubation with low-density lipoproteins. After extraction of the cellular lipids with hexane-isopropanol (3:2, v/v), the cholesteryl esters were identified and quantified by isocratic HPLC. Unesterified cholesterol and its esters were eluted with acetonitrile-isopropanol (50:50, v/v) on a Zorbax ODS column within 25 min and detected at 210 nm. Cholesteryl heptadecanoate was used as an internal standard. The detection response is linear in the analytical range of interest; the overall coefficients of variation are less than 8% and the detection limit is between 50 and 150 ng. The results demonstrate that HPLC is suitable for the determination of cellular cholesteryl ester profiles and could usefully contribute to the understanding of the mechanism of foam cell formation during the development of atherosclerosis. This method can also be applied to all experimental systems involving the study of cholesteryl esters. PMID- 2584345 TI - Catecholamine measurements in urine by high-performance liquid chromatography with amperometric detection--comparison with an autoanalyser fluorescence method. AB - In order to validate different methods of measuring urinary catecholamines (norepinephrine, epinephrine and dopamine) in humans, methods based on separation of catecholamines using reversed-phase or cation-exchange high-performance liquid chromatography with electrochemical detection were compared with an autoanalyser based fluorescence method. Different methods for pre-chromatography sample purification were also studied. For measurements of urinary catecholamines, the reversed-phase-based chromatographic techniques studied were found to give less reliable results than cation-exchange chromatography, even if one of them (Clin Rep Urine Catecholamine Kit) gave almost as precise estimates. The autoanalyser technique yielded good results. It is concluded that cation-exchange chromatography with an appropriate sample work-up procedure (a combination of organic solvent extraction and alumina adsorption) is a reliable and accurate method for analyses of urinary catecholamines. PMID- 2584346 TI - Measurement of methionine enkephalin and leucine enkephalin in rat brain regions by high-performance liquid chromatography with coulometric electrochemical detection. AB - A method is described for the determination of two pentapeptides, methionine enkephalin (H-Tyr-Gly-Gly-Phe-Met-OH) (ME) and leucine enkephalin (H-Tyr-Gly-Gly Phe-Leu-OH) (LE) in discrete rat brain regions. Separation and quantitation were performed by reversed-phase high-performance liquid chromatography with coulometric detection. Perchloric acid extracts of the tissue after enzyme inactivation by heat treatment were passed through a normal-phase solid-phase extraction diol (COHCOH) column, and endogenous ME and LE were subsequently eluted with methanol. The mobile phase was 1-propanol-phosphate buffer (pH 5.5) (9:91). Eluted samples were detected electrochemically using dual coulometric electrodes operated in screen mode. Each of these enkephalins gave a linear response over the range 40-160 ng/ml cerebellar homogenate (0.8-3.2 ng absolute amount on column). Analytical recoveries of synthetic ME and LE, added to the homogenates, were 70 +/- 3 and 70 +/- 10%, respectively, when compared with enkephalins dissolved in water. The mean between-assay coefficients of variation for synthetic ME and LE were lower than 10.7 and 7.4%, respectively, over the concentration range studied. The within-assay coefficients of variation for synthetic ME and LE were 11.4 and 9.5%, respectively, at the lowest concentration. The present method has been applied to a study determining the levels of endogenous ME and LE in discrete rat brain regions. PMID- 2584347 TI - Determination of quinonoid dihydrobiopterin by high-performance liquid chromatography and electrochemical detection. AB - Sodium bisulphite is shown to react with quinonoid dihydrobiopterin to form a stable adduct. Sodium bisulphite does not react with tetrahydrobiopterin. Quinonoid dihydrobiopterin reacts with dithioerythritol to form tetrahydrobiopterin, whereas the quinonoid dihydrobiopterin bisulphite adduct does not. Using these properties we have developed an indirect method for the quantitative measurement of quinonoid dihydrobiopterin. The method requires division of a sample into two. Dithioerythritol is added to one half (a). This converts quinonoid dihydrobiopterin to tetrahydrobiopterin and prevents the oxidation of tetrahydrobiopterin. Measurement of the tetrahydrobiopterin content of this sample by electrochemistry following high-performance liquid chromatographic separation (with dithioerythritol present in the mobile phase to prevent autoxidation of the tetrahydrobiopterin on column), therefore provides a total value of the tetrahydrobiopterin plus quinonoid dihydrobiopterin present within the original sample. Sodium bisulphite is added to the other portion of the sample (b), followed immediately by dithioerythritol which prevents autoxidation of the remaining tetrahydrobiopterin. The bisulphite reacts with the quinonoid dihydrobiopterin present and the quinonoid dihydrobiopterin-bisulphite adduct is no longer detected by electrochemistry at the retention time of tetrahydrobiopterin. Using reversed-phase high-performance liquid chromatography and redox electrochemical detection, measurement of tetrahydrobiopterin in the absence (a) and presence (b) of bisulphite enables the concentration of quinonoid dihydrobiopterin to be calculated by subtraction (a - b). This method is shown to be quantitative and preliminary experiments demonstrate that it can be adapted for biological samples. PMID- 2584349 TI - Integrity in submitting manuscripts. PMID- 2584348 TI - Development and evaluation of monoclonal antibody-based immune electron microscopy for diagnosis of adenovirus types 40 and 41. AB - Immune electron microscopy based on monoclonal antibodies was developed and evaluated for diagnosis of adenovirus type 40 and adenovirus type 41 directly from clinical specimens. One adenovirus type 40 monoclonal (5-8) and one adenovirus type 41 monoclonal (5-15) were found to react to high titre with homotypic but not heterotypic antigen. These monoclonals were tested on a coded batch of 20 stools which contained adenovirus type 40 or adenovirus type 41. The results showed that 5/6 adenovirus type 40 and 13/14 adenovirus type 41 strains were correctly serotyped but one strain of each type failed to react with either serum. A wide variation in the numbers of virions bound to positive grids was observed. A further coded batch of 27 specimens, a mixture of subgenus F (i.e. type 40 or 41) or non-subgenus F adenoviruses, was then tested. There was complete serotype concordance with reference results for 16/19 subgenus F strains and all 8 non-subgenus F adenoviruses gave negative results. However, three subgenus F adenoviruses also gave negative results. In conclusion, monoclonal antibody-based immune electron microscopy accurately distinguished adenovirus type 40 from adenovirus type 41 and both viruses from other adenovirus serotypes in clinical specimens and will therefore be useful in the diagnosis of adenovirus gastroenteritis, but some strains may be missed, presumably because of antigenic variation in surface epitopes. PMID- 2584350 TI - Oxandrolone in constitutionally delayed growth, a longitudinal study up to final height. AB - Twenty-seven prepubertal boys and 9 prepubertal girls with constitutionally delayed growth were treated with the anabolic steroid oxandrolone for 12 months and followed until they reached final height. Sixteen boys were treated with a mean dose of 0.12 mg/kg.day [low dose (LD)] and 11 boys with a mean dose of 0.22 mg/kg.day [high dose (HD)]. The girls were treated with a mean dose of 0.1 mg/kg.day. Thirteen boys and 9 girls served as controls. On oxandrolone the mean height velocity increased from 4.0 to 8.6 (boys, LD), from 4.3 to 8.9 (boys, HD), and from 4.3 to 8.3 cm/yr (girls). The immediate posttreatment height velocity was significantly higher than the pretreatment height velocity (P less than 0.05), regardless of whether the patients had entered puberty. On oxandrolone the mean ratios of change in bone age/change in chronological age were 2.0 (boys, LD), 2.3 (boys, HD), and 2.0 yr/yr (girls) and continued to be accelerated during the 6 months after treatment. Height predictions at the onset of treatment and after 6 months off treatment were calculated by three different methods: Bayley Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner Mark II (T II). In the boys (LD) mean height predictions increased significantly by the methods of BP (3.3 cm) and RWT (2.9 cm), but not by the method of T II (0.6 cm). In the boys (HD) no significant change in height predictions was noted. In the girls mean height predictions remained unchanged by BP and RWT, but decreased significantly by T II (-2.5 cm). The difference between final height and initial height prediction was taken as a measure of the influence of the treatment on adult height. In all three treatment groups the difference between final height and initial height prediction, calculated with all three methods, did not differ from the control group. We conclude that oxandrolone treatment for 1 yr has no effect on adult height. In spite of this, the use of an anabolic steroid such as oxandrolone may still have value, as an increase in height velocity and an earlier onset of puberty may benefit short children suffering from psychological problems due to delay of growth and development. PMID- 2584351 TI - Low levels of thyroglobulin messenger ribonucleic acid in congenital goitrous hypothyroidism with defective thyroglobulin synthesis. AB - We characterized the virtual absence of immunoassayable thyroglobulin (Tg) in the serum and thyroid gland of two siblings (MA, JNA) and one nephew (RSS) from a family without inbreeding or familial goiter. Diagnosis of defective Tg gene expression was based on findings of normal PBI and low serum T4, low or normal serum T3, negative perchlorate discharge test, and virtual absence of the serum Tg response to challenge by bovine TSH. This conclusion was confirmed by analysis of proteins in the goiter extracts. Only minute amounts of immunoassayable Tg were detected by RIA (MA, 0.11; JNA, 0.19 mg/g tissue; compared to 70-90 mg/g in normal thyroid tissue). Gel filtration in Sephacryl S300 showed the absence of a normal Tg peak at 280 nm and concentration of label mostly on albumin. A minor intermediate peak of radioactivity was also detected, with the size of, approximately, normal Tg. Sodium dodecyl sulfate-agarose gel electrophoresis indicated the absence of Tg dimer and monomer, and Western blotting and immunoelectrophoresis confirmed this finding. Dot blot quantification of Tg and thyroid peroxidase mRNA indicated decreased hybridization of the patients' mRNA (MA, 44%; JNA, 63%) with phTgM2 (Tg probe) and increased hybridization (MA, 191%; JNA, 182%) with the pM5 (thyroid peroxidase probe) compared with control thyroid tissue. Dot blot analysis of Tg mRNA from the two siblings weakly hybridized with 3' and 5' Tg probes. RNA analysis by means of Northern transfer showed a clear signal of hybridization with Tg probe (phTgM1) in the 8- to 9-kilobase range, corresponding to the normal size Tg mRNA. No major polymorphisms were noted in Southern blotting, using seven restriction endonucleases. We conclude that no gross alteration of the 5' region of Tg gene was present in these patients. Ultrastructural examination of the thyroid tissue indicated that the rough endoplasmic reticulum was not augmented, nor were the cisternae of rough endoplasmic reticulum dilated. The defect observed in these goiters is diminished tissue concentration of Tg mRNA with defective translation. However, small amounts of functionally active Tg could be synthesized, iodinated, and immediately hydrolized, yielding mostly T3, owing to the intense tissue stimulation by TSH. PMID- 2584352 TI - Insulin-like growth factor-II in nonislet cell tumors associated with hypoglycemia: increased levels of messenger ribonucleic acid. AB - The role of insulin-like growth factor-II (IGF-II) in the hypoglycemia associated with nonislet cell tumors is controversial. In this study we have addressed this question by measuring the IGF-II mRNA levels in extracts of these tumors. Hybridization of a 32P-labeled IGF-II cDNA to a Northern blot of RNA from three nonislet cell tumors associated with hypoglycemia (a hemangiopericytoma, fibrosarcoma, and malignant mesenchymal tumor) demonstrated six hybridizing bands, 6.8, 5.6, 4.7, 3.6, 2.6, and 2.1 kilobases in length. These bands were similar to those described by others in a range of tumors and normal tissues. Tissue IGF-II mRNA levels were quantitated using a solution hybridization/RNase protection assay. IGF-II mRNA levels in the tumors were similar to the level present in one line of human hepatoblastoma-derived Hep G2 cells, 5- to 6-fold higher than that in another line of Hep G2 cells, and 2- to 3-fold higher than that in term placenta. In contrast, little or no IGF-II mRNA was detected in a nonfunctioning islet cell adenoma or normal spleen. There was no evidence for amplification of the IGF-II gene in the one tumor in which it was sought. These data suggest that nonislet cell tumors associated with hypoglycemia produce large amounts of IGF-II mRNA and that this IGF-II mRNA appears to be the product of an IGF-II gene, which is apparently normal in the region encoding mature IGF-II peptide. PMID- 2584353 TI - Water and salt conservation in the human fetus and newborn. I. Evidence for a role of fetal prolactin. AB - A study was performed on 94 women delivering at 34-44 weeks gestation, whose pregnancies were uncomplicated to determine the role of PRL in human fetal and neonatal salt and water conservation. Ultrasonic estimation of amniotic fluid (AF) volume and sampling of maternal blood, AF, cord blood, and 2-h neonatal blood were performed to analyze PRL, osmolality, sodium ion concentration ([Na]), and blood solids [hematocrit (Hct), total serum solids (tss), and total protein concentration]. In this report, which addresses the role of fetal PRL, Pearson correlations showed the following significant relationships: 1) approximation of cord serum osmolality and [Na] in cord and maternal serum, as well as parallel changes in cord blood Hct, tss, and total protein; 2) reduced estimated AF volume and increased AF osmolality in the face of elevated cord serum osmolality and [Na]; 3) a shift toward normal in cord Hct and tss over the first 2 h of neonatal life after an initially increased or decreased cord serum osmolality, [Na], Hct, or tss; and 4) relationship between fetal pituitary PRL levels of 230 micrograms/L or less and cord serum osmolality, [Na], and Hct. The entire range of cord serum PRL levels correlated with changes in AF osmolality and [Na] as well as with neonatal changes in Hct and tss. These findings support the hypotheses that osmotic equilibrium exists between maternal and fetal circulations; that disturbances in this balance lead to changes in fetal and neonatal water excretion; and that fetal PRL, stimulated by increases in cord serum osmolality and [Na], acts as an antidiuretic, leading to restoration of the offspring's extracellular fluid volume. PMID- 2584354 TI - The effects of RU 486 on immune function and steroid-induced immunosuppression in vitro. AB - The effect of RU 486 [17 beta-hydroxy-11 beta-(4-dimethylamino-phenol)17 alpha (prop-1-ynyl)estra- 4,9diene-3-one] on [3H]thymidine incorporation into Concanavalin-A-stimulated human peripheral blood mononuclear cells and its influence on the suppressive effects of cortisol and progesterone were investigated. Cortisol suppressed lymphocyte thymidine incorporation at 10(-5), 10(-6), and 10(-7) M (17.6%, 20%, and 38% of control, respectively; P less than 0.01). Cortisol-induced suppression was reversed when low concentrations of RU 486 (10(-7) and 10(-6) M) were added. RU 486 at 10(-5) M further suppressed lymphocyte thymidine incorporation when added to cultures with cortisol. Progesterone significantly inhibited lymphocyte thymidine incorporation at 10(-5) M (8.2% of control; P less than 0.01). No reversal of progesterone-induced suppression of thymidine incorporation was seen when RU 486 was added to cultures; rather, further suppression of thymidine incorporation was seen. RU 486 alone in culture at concentrations achieved therapeutically (10(-5) M) significantly inhibited thymidine incorporation (7.2% of control; P less than 0.01). These findings suggest that RU 486 may have dose-dependent mixed agonist/antagonist effects on cortisol-induced immunosuppression. The lack of an antagonist effect of RU 486 on progesterone suggests that progesterone's immunosuppressive effects may not be receptor mediated. Finally, our findings would suggest that some immunosuppression may be seen at currently used doses of RU 486. PMID- 2584355 TI - Progesterone and estradiol modulate interleukin-1 beta messenger ribonucleic acid levels in cultured human peripheral monocytes. AB - The relationship between the endocrine system and immune monokines, such as interleukin-1 (IL-1), is of increasing interest. IL-1, a protein secreted by peripheral monocytes and tissue macrophages, mediates a wide variety of immune responses, and its production appears to be inversely related to the level of gonadal steroids. In this report, we have investigated the relationship between estradiol and progesterone concentrations and the level of IL-1 beta mRNA in cultured human peripheral monocytes and pelvic macrophages. Human peripheral monocytes, isolated during the luteal phase of the menstrual cycle, were activated with lipopolysaccharide (10 micrograms/mL). Cellular RNA was isolated and analyzed by Northern analysis using an 800-basepair IL-1 beta cDNA probe. Hybridization with 32P-labeled probe showed maximal levels of IL-1 beta mRNA occurring between 3 and 7 h of culture. Cultures of lipopolysaccharide-activated human peripheral monocytes incubated for 3-6 h with increasing amounts of progesterone or estradiol (0-10(-5) M) in the presence of either 5% fetal calf serum or 0.1% BSA demonstrated an inverse relationship between IL-1 beta mRNA levels and steroid concentration. In both cases, IL-1 beta mRNA levels decreased by 80-90% as the progesterone concentration increased to 10(-5) M and by 70-90% as the estradiol concentration increased similarly. A similar 80% decrease in IL 1 beta mRNA was observed with peritoneal macrophages incubated with increasing amounts of progesterone. This reciprocal relationship between IL-1 beta mRNA and gonadal steroids may have important ramifications in reproductive biology for both embryonic implantation and fetal survival as well as for clinically relevant changes in bone mass. PMID- 2584357 TI - Cotinine and nicotine inhibit human fetal adrenal 11 beta-hydroxylase. AB - The effects of nicotine and cotinine on fetal adrenal 11 beta- and 21-hydroxylase were examined using enzymatic and spectral techniques. The addition of nicotine or cotinine to preparations of adrenal mitochondria yielded a type II cytochrome P-450 binding spectrum. The apparent spectral dissociation constants (Ks) for nicotine and cotinine binding to mitochondrial cytochrome P-450 were 20 and 19 microM, respectively. The addition of nicotine to preparations of adrenal microsomes yielded a type II cytochrome P-450 binding spectrum, with an apparent Ks of 70 microM. Adrenal mitochondrial 11 beta-hydroxylase was assayed by measuring the conversion of deoxycorticosterone to corticosterone. Nicotine and cotinine competitively inhibited 11 beta-hydroxylase, with apparent Michaelis Menten inhibition constants (Ki) of 9.9 and 9.0 microM, respectively. Nicotine competitively inhibited microsomal 21-hydroxylase, with an apparent Ki of 110 microM. Cotinine, in concentrations as high as 1 mM, did not inhibit 21 hydroxylase. These results suggest that nicotine and cotinine inhibit 11 beta hydroxylase by binding to the heme iron of the cytochrome P-450 component of this enzyme system. Inhibition of 11 beta-hydroxylase could contribute to the altered pattern of steroidogenesis observed in smokers. PMID- 2584356 TI - Apolipoprotein-E2 and hyperlipoproteinemia in noninsulin-dependent diabetes mellitus. AB - The association of apolipoprotein-E2 (apoE2) with hyperlipoproteinemia (HLP) was investigated in 23 noninsulin-dependent diabetes mellitus patients with apoE2 and 24 nondiabetic controls with apoE2. The frequency of HLP was significantly higher in diabetic subjects with apoE2 (73.9%) than in nondiabetic controls (37.5%). HLP in nondiabetic subjects with apoE2 included only type IV (n = 9), whereas HLP in diabetic subjects with apoE2 included type IIb (n = 1), type III (n = 7), and type IV (n = 9). Diabetic patients with apoE2 were characterized by increased levels of plasma triglyceride, total cholesterol (chol), very low density lipoprotein (VLDL)-chol, and apoE and an increased VLDL-chol/VLDL-triglyceride ratio, i.e. the accumulation of remnants. In addition, fasting plasma glucose and hemoglobin-A1 levels were significantly higher in hyperlipoproteinemic diabetic patients with apoE2 than in normolipidemic diabetic patients with apoE2. It is concluded that diabetes (poor metabolic control) predisposes apoE2 (epsilon 2) carrying subjects to HLP (particularly type III) and that apoE2 may be one factor linking diabetes with HLP and cardiovascular disease. PMID- 2584358 TI - Serum vitamin D metabolites are not responsible for low turnover osteoporosis in chronic liver disease. AB - We measured the concentrations of vitamin D-binding protein (DBP), total 25 hydroxyvitamin D, total 1,25-dihydroxyvitamin D [1,25-(OH)2D], and free 1,25 (OH)2D in sera of 107 patients with histologically proven chronic liver disease. Bone density measurements and dynamic skeletal histomorphometry were also performed. Osteoporosis, as defined by arbitrary criteria, was found in 42 patients (39%), while no patient had osteomalacia. Serum concentrations of vitamin D-binding protein, 25-hydroxyvitamin D, total 1,25-(OH)2D, and free 1,25 (OH)2D were reduced in patients with cirrhosis, but not in the noncirrhotic patients. Bone formation rates, which were low in 55 patients (51%), were correlated with liver functions, but not with the concentrations of either vitamin D metabolite. A subgroup of 44 patients with low serum 1,25-(OH)2D concentrations and low bone formation rates failed to show an appropriate increase in serum bone Gla protein after 1,25-(OH)2D3 administration even though serum concentrations of 1,25-(OH)2D rose normally. These data suggest that the bone disease in patients with hepatic disorders is not related to the serum concentrations of vitamin D metabolites or the effect of these metabolites on osteoblast function. PMID- 2584359 TI - Arteriographic ablation of cervical parathyroid adenomas. AB - In some cases of primary hyperparathyroidism, in particular where neck exploration has been unsuccessful, an alternative to surgical therapy may be desirable. We studied the acute and chronic metabolic effects of attempted angiographic destruction by angiographic contrast infusion of solitary parathyroid adenomas in 18 patients with symptomatic disease. Fourteen patients had failed prior surgery; 4 patients had not undergone prior surgery but were extremely high surgical risks. Cervical adenomas were present in 17 of 18 subjects; mediastinal adenoma in 1 of 18. Sixteen patients underwent selective parathyroid venous catheterization, which facilitated subsequent arteriographic localization. Selective arteriographic localization and attempted angiographic ablation were performed in all subjects with standard contrast, renografin-60. Laboratory studies, including serum calcium and PTH, were frequently performed before and after attempted angiographic parathyroid ablation. In all patients serum calcium fell to normal or subnormal levels within 48 h of attempted ablation. Prolonged follow-up (mean, 35.1 months) revealed that ablation was curative in 12 of 18 (sustained normocalcemia) and partially effective in 1 of 18 patients. For the entire group serum calcium fell from 3.14 +/- 0.07 at presentation to 2.42 +/- 0.07 mmol/L at the end of follow-up (or before surgery in unsuccessful cases; P less than 0.001). In 4 of 5 failed cases hypercalcemia recurred within 2 weeks. All 5 failed cases underwent curative surgery, aided by accurate localization achieved during angiographic procedure. Several transient complications and 1 case of permanent hypoparathyroidism were noted. We conclude that angiographic ablation of cervical parathyroid adenomas can be considered as an extension of diagnostic angiographic procedures in selected cases of primary hyperparathyroidism who have failed prior surgery of possibly in rare cases where surgery is contraindicated. PMID- 2584360 TI - Cocaine effects on pulsatile secretion of anterior pituitary, gonadal, and adrenal hormones. AB - Pulse frequency analysis of LH, PRL, testosterone, and cortisol was carried out with the Cluster Analysis Program in eight male cocaine abusers and eight aged matched normal men. Four of the eight cocaine abusers had hyperprolactinemia (range, 22.08-44.65 micrograms/L). Cocaine users as a group had significantly higher mean peak height (P less than 0.02) than control subjects. Cocaine users with hyperprolactinemia had higher mean peak height than control subjects or cocaine users with normal PRL levels (P less than 0.01). Cocaine users with hyperprolactinemia also had higher mean amplitude increments than control subjects (P less than 0.02). Cocaine users with hyperprolactinemia had a higher mean valley than controls (P less than 0.01) and cocaine users with normal PRL levels (P less than 0.03). However, there were no significant differences in PRL peak frequency, peak duration, or interpulse intervals between cocaine users with or without hyperprolactinemia and control subjects. There were minimal differences between cocaine users and control subjects in pulse frequency analysis of LH parameters; the small differences in mean LH levels and average interpulse interval were not in the abnormal range and were probably not biologically significant. No differences between cocaine users and controls were detected for pulse frequency analysis of testosterone or cortisol. Cocaine induced hyperprolactinemia may contribute to disorders of sexual and reproductive function in men who abuse the drug, and recent reports that PRL modulates immune function suggest that cocaine-induced derangements of PRL secretion may also contribute to cocaine-related comorbidity in infectious disease. Since cocaine users with hyperprolactinemia had a higher mean valley as well as a higher peak pulse PRL height than control subjects, but did not have greater PRL pulse frequencies, we conclude that hyperprolactinemia in these men may be due to a cocaine-induced derangement of dopaminergic inhibition of basal PRL secretion. PMID- 2584361 TI - Hashimoto's thyroiditis and HLA in Japanese. AB - To investigate genetic factors involved in the pathogenesis of Hashimoto's thyroiditis (HT; goitrous autoimmune thyroiditis), HLA class I and class II antigens were analyzed in both seropositive HT (99 patients) and seronegative HT (43 patients). The frequency of HLA-DRw53 antigen was increased significantly in both seropositive HT (antigen frequency, 0.83; relative risk, 33.3; P less than 0.0002; corrected P less than 0.001) and seronegative HT (antigen frequency, 0.81; relative risk, 3.02; P less than 0.01; corrected P less than 0.05). The etiological fraction values for HLA-DRw53 in seropositive HT and seronegative HT were 0.58 and 0.54, respectively. An increased frequency of HLA-DQw4 and a decreased frequency of HLA-DQw1 were observed in patients with seronegative HT. These data suggest that susceptibility to HT is primarily associated with HLA DRw53 and that HLA-DQ alleles may control the production of autoantibodies to the thyroid gland. The mode of inheritance of disease susceptibility for HT (controlled by a major gene in linkage disequilibrium with HLA-DRw53) was investigated by the method of Thomson and Bodmer, and it was suggested that disease susceptibility was inherited in a dominant manner. PMID- 2584362 TI - [Changes in spinal evoked potentials following local cooling of the spinal cord in the cat]. AB - Potentials evoked by stimulation of the ulnar nerve and the thoracic cord were recorded in the cervical cord of Nembutalized, curarized cats. The sites of the spinal cord stimulated or recorded therefrom were cooled, all together or independently, in 30 cats, and the effects of the cooling on the evoked potentials were investigated. In all cases, the peak latency tended to increase. On the other hand, the amplitude gradually decreased in the cats in which the stimulation site was cooled, gradually increased in the cats in which the recording site was cooled, and transiently increased when the whole area extending from the stimulation site to the recording site was cooled. In 20 cats, the effects of cooling on the anoxic spinal cord were studied. In the hypothermic cats, the evoked potentials disappeared in 24 min, and in the normothermic cats in 13 min. The difference was statistically significant (p less than 0.01). This indicates that cooling could counteract the effects of anoxia to a certain extent. PMID- 2584363 TI - [The 1H-NMR evaluation of biomechanical function in human lumbar disc]. AB - The purpose of this study was to determine the usefulness of relaxation time of nuclear magnetic resonance in evaluating biomechanical functions of human lumbar discs. Using L3-L4 disc-body units obtained from fresh human cadavers en bloc, proton density imaging was performed with a NMR-CT. Furthermore, intradiscal pressure, tan delta, dynamic stiffness, and relaxation time were measured. The results were as follows: Proton density imaging was useful in detecting the degeneration of the human lumbar disc. Intradiscal pressure, tan delta, and relaxation time decreased with advancing age whereas dynamic stiffness increased. The correlation coefficient of relaxation time to tan delta and dynamic stiffness was 0.80 (p less than 0.01) and -0.67 (p less than 0.05), respectively, which reflected dynamic viscoelasticity of the human lumbar disc. In conclusion, relaxation time seems to be useful in evaluating biomechanical functions of human lumbar discs. PMID- 2584364 TI - [An attempt at angiographic characterization of pulmonary arterial distribution in small-sized lung cancers originating in the peripheral region of the lung]. AB - In order to clarify the distribution pattern of the pulmonary vessels, which are one of the supply sources of small-sized lung cancers, we studied tumors of less than 3.5 cm in diameter, which were made available to our department, by pre operative pulmonary angiography, as well as microangiography of the surgically resected lung. Morphological study of the pulmonary arterial trees in various tumors revealed that they may be classified into either highly vascular or poorly vascularized subtypes. In addition to the morphological study of the pulmonary arterial trees, a correlative study of the extent of the area covered with the intraneoplastic pulmonary arteries and the tumor area was attempted. In the highly vascularized group, moderate or highly differentiated adenocarcinoma or squamous cell carcinoma, or alveolar cell carcinoma were observed. In the latter group, poorly differentiated adenocarcinoma, large cell or small cell type undifferentiated carcinoma were observed. Thus it is concluded that visualization of vessel distribution in the tumor parenchyma is made possible by the technique of selective pulmonary angiopathy which leads to identification of the detailed histological patterns and degree of differentiation. This may offer very versatile diagnostic information on the efficacy of selective pulmonary anti cancer infusion therapy against small-sized lung cancers which originate mainly in the peripheral region. PMID- 2584365 TI - A comparison of frequencies between mouse T cells and B cells which are mutually interactive and specific to each other. AB - Repertoire sizes of T cells and B cells were estimated by frequency studies using mouse helper T cell clone D10G4.1 (D10 for short) and monoclonal antibodies raised against the antigen recognition structures on D10 cells. The soluble form of these antibodies was capable of activating D10 cells to proliferate in the presence of exogenous IL-1. Moreover, among the heterogeneous peripheral T cells, there is a population of cells which respond to those antibodies. Normal spleen B cells were non-clonally activated by LPS in limiting dilution cultures and the supernatant was tested for its activation capacity on D10 cells. Precursor frequencies of B cells which produce D10 activating antibodies were in the range of one in millions. The presence of D10 cells in the limiting dilution cultures increased this frequency by a factor of more than ten. For the estimation of frequencies of a given T cell clone which is activated by anti-D10 antibodies, normal spleen T cells were activated either by beads coupled monoclonal antibodies or by Con A followed by specific soluble antibodies in the limiting dilution cultures, and thereafter specific proliferation was assayed. A group of monoclonal anti-receptor antibodies gave rise to a single hit curve with relatively low frequency of one in 10(4) to 10(5). Another group of antibodies revealed in addition to the low frequency population, a higher frequency population of one in thousands. The data taken together suggest the frequencies of mutually interactive B and T cells are in the range of one in 10(4) to 10(5), while among T cells, there can be seen another population of cells of ten to a hundred fold higher frequency. Consequently, direct idiotype-antiidiotypic interactions between lymphocytes should occur only once in 10(8) to 10(10) cells in the normal unstimulated immune system. Thus, it is more likely that interactions will take place between cells of more degenerated specificities. The implications of these findings in favour of multiple levels of connection among T cells which reflect the multiple levels of affinity of the recognition complex of T cells are discussed. PMID- 2584366 TI - [A study of bronchial sensitivity and bronchial reactivity using Astograph and transcutaneous oxygen tension in asthmatic children. The problems of simultaneous measurement]. AB - Bronchial sensitivity and reactivity in 60 patients with bronchial asthma was measured using the Astograph and simultaneous transcutaneous oxygen tension [PtcO2]. In spite of increasing respiratory resistance, there were some cases in which PtcO2 did not show remarkable decrease. The PtcO2 percentage was defined as (basal value of PtcO2 - bottom value of PtcO2)/(basal value of PtcO2). The correlation between PtcO2% and the basal value of PtcO2 was relatively high (r = 0.42, n = 58, p less than 0.005). The correlation between PtcO2% and V50/Ht or V25/Ht was also relatively high (r = 0.41, n = 45, p less than 0.01, r = 0.49, n = 45, p less than 0.001, respectively). In some cases of small airway obstruction or low basal value of PtcO2, was smaller. The patients of over 70% in FEV1.0/VCP were in accord with that of over 70 mmHg in the basal value of PtcO2. The results suggest the recommended basal value of PtcO2 to measure bronchial sensitivity and reactivity may be over 70 mmHg. PMID- 2584367 TI - [Regulation of ferritin and transferrin synthesis in hepatocytes depending on iron status of rats]. AB - In order to examine the control mechanism of ferritin (Fr) and transferrin (Tf) synthesis depending on intracellular iron levels, the rate of 14C-leucine incorporation into those proteins was investigated by cell culture of isolated hepatocytes obtained from iron deficient, iron injected and control rats. The effects of iron (ferric ammonium citrate: FeAc) and (diferric Tf: 2FeTf) or desferrioxamine (Dfo) in culture media were also examined. Serum iron, TIBC and Hb levels of iron deficient rats, which were fed an iron deficient diet for 2 and 4 weeks were significantly lower than the control. However serum iron and TIBC levels of iron injected rats which had received 30 and 45 mg iron as iron dextran 18 h before sacrifice were approximately ten times higher than the control group. The time course of 14C-leucine incorporation into Fr and Tf was investigated at the 60, 120 and 180 minutes stages of the culture. Fr synthesis was increased by the amounts of iron injected, whereas Tf synthesis showed a negative response to iron. The 14C activities in Fr and Tf detected from culture media were proportional to those in hepatocytes. The percentage of nonglycosylated Fr was 82.0-91.4% for total Fr in the culture media in every experiment, which was measured by the affinity of glycosylated Fr to Con A-Sepharose (Con A). This result suggested the leakage of cytosol Fr through the cell membrane instead of specific secretion of the sialyl protein. The efficiency of Fr and Tf synthesis was positively or negatively proportional to cellular iron contents respectively. And the curves of 14C-leucine incorporation into both proteins, calculated as the sum of those in hepatocytes and culture media intersected at the point between the 30 mg iron injected and control groups. The addition of FeAC or 2FeTf into the culture media had an indistinct effect on Fr and Tf synthesis, whereas there was a significant decrease for Fr and a slight increase for Tf formations in the Dfo supplement. These results showed the influence of cellular iron levels in Fr and Tf synthesis. PMID- 2584368 TI - Electrophoretic karyotypes of Torulopsis glabrata. AB - Chromosome-sized DNA molecules of clinical isolates of Torulopsis glabrata were resolved by a pulsed-field electrophoretic method, contour-clamped homogeneous electric fields. With the conditions established in this study, 8 to 12 bands (ranging from 445 to 3,000 kilobases) were observed. There were differences in the intensities and migrations of bands, consistent with T. glabrata being either haploid or diploid. A total of 22 distinctive electrophoretic patterns were noted among single isolates of T. glabrata recovered from 33 patients. When strains were delineated by an electrophoretic pattern, individuals usually harbored only one strain. PMID- 2584369 TI - Pasteurella caballi, a new species from equine clinical specimens. AB - The name Pasteurella caballi is proposed for a group of organisms represented by 29 strains isolated from respiratory and other infections in horses. P. caballi strains are gram-negative, oxidase-positive, nonmotile, fermentative rods with the key characteristics of the genus Pasteurella. These strains differed from other Pasteurella species in that all were aerogenic and catalase negative, and some strains produced acid from myo-inositol and L-rhamnose. The levels of DNA relatedness of 28 P. caballi strains with labeled DNA from the proposed type strain averaged 91 and 85% (hydroxyapatite method at 55 and 70 degrees C). P. caballi was 13 to 53% related to strains representing 22 other species of the family Pasteurellaceae. The guanine-plus-cytosine content of the DNA of four strains was 41 to 42 mol%. The type strain is 83851 (=ATCC 49197). PMID- 2584370 TI - Turnover of nontypable Haemophilus influenzae in the nasopharynges of healthy children. AB - The nasopharyngeal Haemophilus influenzae flora of healthy children in a day care center was analyzed by repeated sampling during 4 winter months. The average carrier rate was 39%, but 74% of the children became colonized at some time during the study. The H. influenzae isolates were identified by capsular type, biotype, and multilocus enzyme electrophoresis. The turnover of the flora in individual children and in the day-care group was characterized. Four patterns of colonization were defined among the 38 children and 49 H. influenzae strains. Depending on the persistence in the group, the strains were designated as endemic, i.e., shared between several children on several occasions, or as epidemic, i.e., occurring only once but in several children. The individual hosts had two patterns; resident strains persisted for 2 weeks or more, and transient strains showed no evidence of persistence. The results suggest that there is considerable sharing of certain nontypable H. influenzae among healthy children in day care, whereas other strains remain restricted to a single host. The properties of host and bacteria determining these patterns remain to be defined. PMID- 2584371 TI - Enzyme-linked immunosorbent assay and immunoblot analysis of the immunoglobulin G response to whole-cell and lipooligosaccharide antigens of Pasteurella pneumotropica in laboratory mice with latent pasteurellosis. AB - The immunoglobulin G (IgG) response to whole-cell and lipooligosaccharide (LOS) antigens of Pasteurella pneumotropica was evaluated in mice with latent pasteurellosis by enzyme-linked immunosorbent assay (ELISA) and immunoblots. Antibodies to cell wall proteins of P. pneumotropica also reacted with several protein antigens from isolates of Actinobacillus spp. and other pasteurellae. Conversely, antibodies to LOS antigens of P. pneumotropica demonstrated no cross reactivity with LOSs of other Pasteurella or Actinobacillus species. IgG to cell wall proteins was detected initially by ELISA 4 weeks after experimental oronasal inoculation of specific-pathogen-free mice; antibody to LOSs was first detected 7 weeks after infection and at that time exceeded titers to other cell wall antigens. Naturally infected conventional mice from a colony with endemic latent pasteurellosis had high IgG titers to P. pneumotropica antigens at 8 to 10 weeks of age, and, as in the experimentally infected mice, antibody to LOSs predominated. Thus, LOSs of P. pneumotropica can be used as an ELISA or immunoblot antigen to detect serospecific antibodies in laboratory mice with latent pasteurellosis. PMID- 2584372 TI - Human antibody response to Campylobacter jejuni flagellin protein and a synthetic N-terminal flagellin peptide. AB - We measured isotype-specific human antibodies directed against Campylobacter jejuni native flagellin and a synthetic peptide derived from the N-terminal amino acid sequence of the protein by using a microdilution enzyme-linked immunosorbent assay (ELISA). Serum samples from patients with gastrointestinal infection caused by C. jejuni (n = 20) and control samples (number from normal subjects = 20; number from patients with diarrhea other than campylobacter = 20) were tested in this assay. Serum specimens from patients with campylobacter infection showed statistically significant higher isotype-specific antiflagellin antibody titers than control samples did. Detection of immunoglobulin G (IgG) antibodies was less specific (70%) than detection of either IgA or IgM antibodies in infected patients (95%). The sensitivity of testing for any of the isotypes ranged from 64 to 100% in acute-phase serum specimens and 85 to 95% in convalescent-phase serum specimens. An ELISA with an N-terminal synthetic peptide derived from the flagellin protein as antigen was not sensitive (60%) for detecting campylobacter infection but was very specific (97.5%). In conclusion, detection of serum IgA or IgM against C. jejuni flagellin may be a useful marker of infection. Although the N-terminal synthetic peptide was antigenic in a few patients with infection and showed good specificity in the ELISA, additional amino acid sequences with better sensitivity for detecting infection need to be identified. PMID- 2584373 TI - Characterization of coagulase-negative staphylococci by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblot analyses. AB - Coagulase-negative staphylococci are important nosocomial pathogens. At present, no wholly satisfactory typing scheme exists for these organisms. Therefore, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting were assessed as characterization methods. A total of 100 type strains and nontyped isolates representing nine species of coagulase-negative staphylococci were analyzed. Each species had a reproducible, characteristic whole-cell banding pattern when analyzed by either method. These species-specific profiles were obtained for all isolates despite disparate geographical origins and clinical isolation sites. Intraspecies similarities, calculated by using the Dice coefficient, were significantly higher than interspecies similarities. Although some species were more heterogeneous than others, the allocation of isolates to any particular species was reinforced by the high degree of interspecies dissimilarity. Application of SDS-PAGE also distinguished discrete subspecies groups. These groups possessed the characteristic profile of their species but were distinguished by a group of variable polypeptides. Species specific banding patterns were also obtained by immunoblotting of whole-cell polypeptides. Differences between immunoblot and SDS-PAGE profiles could be attributed to variations of antigenicity of particular polypeptides. However, both SDS-PAGE and immunoblotting provided reproducible and sensitive methods for characterization of coagulase-negative staphylococci. Standardization of these techniques could provide the basis for a primary typing scheme. PMID- 2584374 TI - Cerebral phaeohyphomycosis caused by Chaetomium globosum in a renal transplant recipient. AB - A 32-year-old male patient developed headaches, vomiting, blurring of vision, and focal seizures of the left side of the face 2 months after a renal transplant. He developed a brain abscess and died. Direct KOH examination of the brain tissue demonstrated hyaline as well as dematiaceous, septate hyphae. Histologic examination of brain sections revealed polymorphous fungal elements consisting of septate, dark-pigmented hyphae, intercalary and terminal swollen fungal cells, and budding yeastlike cells characteristic of phaeohyphomycosis. Chaetomium globosum was isolated from the brain tissue on all of the fungal media used. This case represents the first histologically and culturally documented phaeohyphomycotic brain infection caused by C. globosum. PMID- 2584375 TI - Diagnostic considerations and interpretation of microbiological findings for evaluation of chronic prostatitis. AB - Seventy-five patients attending a clinic for chronic prostatitis were evaluated by use of lower urinary tract localization cultures. Coagulase-negative staphylococci, alpha-hemolytic streptococci, and diphtheroids were the most common isolates, but none of these organisms were pathogens, based on the absence of bacteriuria or evidence of an inflammatory response in prostatic secretions. Recognized uropathogens were isolated in 12 (16%) of the 75 cases and included Escherichia coli in 6 cases, Enterococcus spp. in 2 cases, and Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter cloacae, and Staphylococcus saprophyticus in 1 case each. Laboratory evaluation of men with chronic prostatitis should concentrate on the isolation and antimicrobial susceptibility testing of bacteria that have an established pathogenic potential in the genitourinary tract. PMID- 2584376 TI - Evaluation of a rapid method of extracting DNA from stool samples for use in hybridization assays. AB - The ability of the Extractor system (Molecular Biosystems, Inc., San Diego, Calif.) to isolate nucleic acid (NA) from stool samples for use in hybridization assays was investigated. Crude NA was recovered from 45 of 50 stool samples by using this system. The amount of NA recovered varied considerably depending on the microbial flora present in the sample (mean +/- standard deviation, 50.2 +/- 46.7 micrograms; range, 2 to 228 micrograms) but did not correlate with the consistency of the sample. Samples containing primarily gram-positive organisms or yeast cells gave lower yields of NA (less than 10 micrograms) than those containing gram-negative bacilli. The five samples which did not yield NA were sterile when cultured aerobically on blood agar plates. Samples of the 45 stools yielding NA were inoculated into broth and grown overnight, and a 10-microliters sample of broth was spotted onto nitrocellulose filters. The NA samples recovered from the Extractor column were applied to nylon membranes by using the Centri-dot system. The NA on the broth blots and the NA on the Centri-dot filters were hybridized with a 310-base-pair probe specific for the 2"-O-aminoglycoside adenylyltransferase [ANT(2")] resistance gene. The Extractor-Centri-dot system demonstrated 61.9% sensitivity and 95.8% specificity in detecting the ANT(2") gene in stool samples containing colonies demonstrating the ANT(2") phenotype. The positive and negative predictive values of the NA blot were 92.8 and 74.2%, respectively. PMID- 2584378 TI - Comparison of four commercial brucella agar media for growth of anaerobic organisms. AB - Four different commercial brucella blood agar plating media (Anaerobe Systems, BBL Microbiology Systems, Remel, and Scott Laboratories) were compared for the abilities to recover anaerobic organisms from clinical specimens and to support the growth of American Type Culture Collection anaerobic stock cultures. Following 24 h of incubation in an anaerobe chamber, Anaerobe Systems prereduced, anaerobically sterilized brucella plates yielded 63% of the total clinical anaerobe isolates, the Scott medium yielded 51%, the Remel medium yielded 42%, and the BBL medium yielded 37%. Poor growth of Peptostreptococcus magnus, P. anaerobius, Fusobacterium necrophorum, F. nucleatum, and pigmented Bacteroides spp. was observed on brucella media obtained from BBL, Remel, and Scott. Data obtained with stock anaerobic cultures showed that Anaerobe Systems plates yielded good growth and produced a larger colony size with all of the strains tested in 1 day, whereas poor growth of Peptostreptococcus spp., B. melaninogenicus, and Fusobacterium spp. was noted on brucella media from BBL, Remel, and Scott. PMID- 2584377 TI - Detection of leptospires in urine by polymerase chain reaction. AB - Primers for polymerase chain reaction (PCR) were synthesized from clones derived from a Leptospira hardjo (type hardjobovis) library. One pair of synthetic oligonucleotide primers was selected for further analysis. Under experimental conditions an amplification was obtained with DNA of Leptospira interrogans of some serovars belonging to serogroup sejroe. However, very little or no amplification was observed with DNA from other serovars of this group. No amplification was observed with DNA from other serogroups, other bacteria, or eucaryotic organisms. Cattle urine, seeded with hardjobovis, was processed in several ways and subsequently subjected to PCR. Boiling of the samples or treatment with detergents appeared to be most effective. Urine samples containing fewer than 10 leptospires gave a positive result in the PCR assay. Twenty urine samples obtained from a slaughterhouse or farm cows were investigated using the PCR assay, culture isolation, dot and quick blot hybridization, and serological tests. This comparative study suggests that amplification by PCR may be a valuable method for the detection of leptospires in cattle urine. PMID- 2584380 TI - Visuwell Reagin, a non-treponemal enzyme-linked immunosorbent assay for the serodiagnosis of syphilis. AB - A urease-based enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of reagin antibodies in serum. Visuwell Reagin (ADI Diagnostics Inc., Rexdale, Ontario, Canada) is a non-treponemal screening test for the serodiagnosis of syphilis which has the benefits of large batch testing, automatability, and objective interpretation of results. Unheated, undiluted sera are incubated in 96-well microtiter plates coated with a modified cardiolipin lecithin-cholesterol antigen. Antibody bound to the plate is detected by an anti human immunoglobulin G-urease conjugate. The procedure consists of three steps, with a total test time of 60 min. Visuwell Reagin ELISA was compared with the Venereal Disease Research Laboratory (VDRL) test and the reagin screening test (RST) with the following results. For ELISA versus the VDRL test, the sensitivities for untreated syphilis (n = 37) were 97.3% for both ELISA and the VDRL test, the confirmatory positive values (n = 79) were 84.8% for ELISA and 72.2% for the VDRL test, and the specificities for normal samples (n = 1,327) were 98.8% for ELISA and 99.5% for the VDRL test. For ELISA versus RST, the sensitivities for untreated syphilis (n = 57) were 94.7% for ELISA and 87.7% for RST, the confirmatory positive values (n = 26) were 96.2% for ELISA and 92.3% for RST, and the specificities for normal samples (n = 1,891) were 99.6% for ELISA and 99.3% for RST. The overall concordance values of ELISA with VDRL test and RST were 96.7 and 97.9%, respectively. The specificity of ELISA compared with that of RST may be underestimated, since confirmatory data were not available for all apparent false-positive samples. Visuwell Reagin had increased sensitivity and similar specificity compared with flocculation tests. PMID- 2584381 TI - Lack of protection against bacterial infections in patients with advanced cancer treated by biologic response modifiers. AB - A survey of patients with advanced cancer treated by biologic response modifiers (BRMs), including (i) recombinant interleukin-2 and lymphokine-activated killer cells, (ii) recombinant interleukin-2 and alpha interferon, and (iii) tumor necrosis factor, was done. A total of 52 patients were reviewed. A total of 73 courses of BRMs were administered. Prior to the initiation of therapy, all patients were infection free and not receiving antibiotics. Twelve patients developed bacteremia during treatment with these BRMs. Five of these 12 patients had catheter-related bacteremia. Six patients had bacteremic infections without an obvious source, and one patient had a urinary tract infection with bacteremia. Staphylococcus epidermidis accounted for six of the isolates. Other organisms were Staphylococcus aureus, group B streptococci, viridans group streptococci, and gram-negative bacilli. This was an unexpectedly high incidence of bacterial infections in patients treated with BRMs. These BRMs have been previously shown to be efficacious against infections (by bacteria and other intracellular organisms) in experimental animals. In this study BRMs did not influence host defense mechanisms or offer protection against bacterial infections. PMID- 2584379 TI - Typing of urogenital, maternal, and neonatal isolates of Haemophilus influenzae and Haemophilus parainfluenzae in correlation with clinical source of isolation and evidence for a genital specificity of H. influenzae biotype IV. AB - Over a period of 6 years, 114 strains of Haemophilus influenzae and Haemophilus parainfluenzae were isolated from genital, mother-infant, or neonatal infections. Their serotypes, biotypes, antibiotic resistance phenotypes, and outer membrane protein (OMP) electrophoretic patterns were characterized and correlated with the various clinical outcomes. Genital H. influenzae and H. parainfluenzae appeared to behave mostly as opportunistic pathogens; for instance, 62% of the cases of endometritis or pelvic inflammatory disease were related to the presence of an intrauterine device. However, as seen clearly in one case, the strains may be sexually transmitted. The analysis of OMP patterns proved to be a very convenient method to seek evidence for the sexual origin of the infection. H. influenzae was more often involved in complicated genital infections than was H. parainfluenzae. Nontypeable and biotype II H. influenzae strains were the more frequent isolates, except in pelvic inflammatory diseases, in which biotype I prevailed, and in mother-infant infections, in which one-fourth of the cases were due to biotype IV. Characterization of H. influenzae isolates did not support a general concept of specific genital strains. However, strains of biotype IV clearly stood out with two characteristics: (i) a peritrichous fimbriation and (ii) a very peculiar homogeneous OMP pattern comprising an OMP of molecular weight approximately 18,000 unique to this biotype. These characteristics were also found in H. influenzae biotype IV strains isolated from genital infections in the United States and used as controls. H. influenzae biotype IV strains may thus correspond to a group somewhat adapted to the genital tract. PMID- 2584382 TI - Application of different chromosomal DNA restriction digest fingerprints to specific and subspecific identification of Campylobacter isolates. AB - Eleven strains comprising representatives of different subspecies, biotypes, and serotypes of Campylobacter jejuni and reference strains of C. coli, C. fetus subsp. fetus, C. hyointestinalis, and C. sputorum subsp. sputorum were studied to assess the utility of different DNA profiles for measuring fine differences between allied bacteria. Strains were compared by analyses of HaeIII and XhoI digest patterns of chromosomal DNA and Southern blot hybridization patterns of XhoI digests obtained with an Escherichia coli 16S + 23S rRNA gene probe. Visual comparisons and numerical analyses of the HaeIII and XhoI digest patterns both revealed clear differences between the five Campylobacter species and between representatives of C. jejuni subspecies and biotypes. Only strains with the same Penner serotype gave identical total digest polymorphisms. The advantages of XhoI total digests and Southern blot hybridization patterns were that they were less complex than the HaeIII patterns and easier to compare visually. However, numerical analysis of XhoI data resulted in reduced discrimination. We conclude that DNA fingerprinting using either HaeIII or XhoI fragment polymorphisms has considerable potential as a generally applicable method for identification of Campylobacter isolates, especially at the infrasubspecific level. PMID- 2584383 TI - Molecular techniques for the detection of Chlamydia trachomatis. AB - A DNA probe assay (PACE; Gen-Probe, San Diego, Calif.) was compared with a culture reference method for the detection of Chlamydia trachomatis. Using stock isolates of each of the 15 serovars (A to K, Ba, L1, L2, and L3) of C. trachomatis, the lower limit of sensitivity for the DNA probe ranged between 1,086 inclusion-forming units (IFU) for serovar E (Bour) to 2,930 IFU for serovar L1 (440), with the only exception being serovar C (TW-3), with which 99 IFU was detected. There was no cross-reactivity with Chlamydia psittaci (Texas turkey) and Chlamydia pneumoniae (TWAR-183). Bacterial and fungal isolates representing 14 species of normal vaginal flora as well as Neisseria gonorrhoeae gave negative results with the DNA probe when tested at a level of 1.5 X 10(7) CFU/ml. In addition, the DNA probe, a direct fluorescent-antibody stain (DFA) (MicroTrak; Syva Corp., Palo Alto, Calif.), and an enzyme-linked immunosorbent assay (Chlamydiazyme; Abbott Laboratories, North Chicago, Ill.) were compared with culture for the detection of C. trachomatis, using 196 clinical cervical samples. Of the 196 samples, 20 (10%) were culture positive. Of the 176 culture-negative samples, 1 was not evaluated by DNA probe and 4, because of a lack of cellular material, were not evaluated by DFA. The sensitivities of the DNA probe, DFA, and enzyme-linked immunosorbent assay were 60, 75, and 85%, respectively, and specificities were 95, 99, and 97%, respectively. Of the false-positive direct results, there was only one specimen with which more than one direct method was positive, and with this specimen all three direct methods were positive. The majority of false-negative results by the direct methods were from specimens which by the culture method gave <100 IFU per culture. PMID- 2584384 TI - Aerobic and anaerobic microbiology of biliary tract disease. AB - A retrospective analysis of the experiences of two military hospitals over 4 years in the recovery of organisms from biliary tract specimens was done. Bacterial growth was obtained in 123 bile specimens. Aerobic and facultative bacteria only were present in 59 specimens (48%), aerobic bacteria only were present in 4 specimens (3%), and mixed anaerobic and aerobic or facultative bacteria were present in 60 specimens (49%). Of 286 isolates recovered, 216 were aerobic or facultative (1.8 per specimen) and 70 were anaerobic (0.6 per specimen). The predominant bacteria were Escherichia coli (71 isolates), group D streptococci (42 isolates), Klebsiella sp. (29 isolates), Clostridium sp. (27 isolates), Bacteroides sp. (28 isolates), and Enterobacter sp. (16 isolates). Polymicrobial infections were present in 108 instances (88%). A higher recovery rate of anaerobes was present in patients with chronic infections than in those with acute infections and did not correlate with the presence of gallstones or use of antimicrobial prophylaxis. PMID- 2584385 TI - "Campylobacter upsaliensis" isolated from cats as identified by DNA relatedness and biochemical features. AB - Campylobacter spp. were isolated from the feces of 20 (58%) of 53 asymptomatic cats during routine physical examination while the cats were maintained in an accredited quarantine facility. Fifteen of these Campylobacter spp. were identified phenotypically as Campylobacter jejuni, and two were identified as C. coli. DNA-DNA hybridization (hydroxyapatite method) was used to confirm the identification of three thermotolerant catalase-negative isolates. They were 80 to 100% related to each other and to the type strain of "C. upsaliensis" in reassociation reactions under optimal conditions and a stringent hybridization criterion. These strains were 75 to 100% interrelated and less than 12% related to type strains of other Campylobacter species. These strains represent the first reported feline isolate of "C. upsaliensis" and show that cats used in biomedical research can harbor this and other Campylobacter species. PMID- 2584386 TI - Evaluation of four newer antimicrobial agents in the Avantage susceptibility test system. AB - Antimicrobial elution disks containing amoxicillin-clavulanic acid (Augmentin), cefotetan, ciprofloxacin, or norfloxacin were tested in the Avantage automated susceptibility test system. Performance was compared against an agar diffusion procedure in a three-site collaborative study. Results of 1,500 comparison with amoxicillin-clavulanic acid showed a full accord (agreement of both systems) of 93.6% and an essential accord (agreement excluding minor discrepancies) of 97.6%. Results for cefotetan showed a full accord of 95.1% and an essential accord of 98.3% by the two methods. Results for both ciprofloxacin and norfloxacin were in full accord for more than 98% of tests with gram-negative bacilli and staphylococci, but tests with enterococci gave 38 and 26.1% minor discrepancies (the result of one method was resistant or susceptible and the result of the other method was intermediate), respectively. The results indicated that the Avantage test system is accurate and reliable and provides appropriate determination of bacterial susceptibility with the four antibiotics tested. PMID- 2584387 TI - Establishment of 2-docosanol as a cellular marker compound in the identification of Mycobacterium xenopi. AB - Sixteen strains of Mycobacterium xenopi were studied by gas chromatography and thin-layer chromatography. Data on the cellular fatty acids, fatty alcohols, mycolic acids, and glycolipids indicated that this bacterium possesses a specific lipid composition. 2-Docosanol, detected in all studied strains, was found to constitute a useful chemical marker in the identification of M. xenopi. PMID- 2584388 TI - Frequency of Staphylococcus intermedius as human nasopharyngeal flora. AB - Staphylococcus intermedius, a veterinary flora and pathogen, has recently been isolated from humans with infected dog bite wounds. The frequency of S. intermedius as a human nasopharyngeal flora was determined by culturing samples from 144 veterinary college staff members. This bacterium was isolated from only one individual (0.7%). It appears that S. intermedius is a true zoonotic opportunistic pathogen. PMID- 2584389 TI - Standardization of yeast inocula with an electronic impedance counter. AB - The standardization of yeast inocula has been identified as an important variable in the performance of reproducible in vitro fungal susceptibility testing. We investigated the precision and accuracy of an electronic particle counter in preparing yeast inocula, with quantitative culture used as a "gold standard." Suspensions of Candida albicans and Torulopsis glabrata standardized with a particle counter at 10(6) counts per ml were highly reproducible when cultured quantitatively (coefficients of variation, 6.7 and 6.8%, respectively). Accuracies of particle counts, compared with those of quantitative culture, were 8.5 and +2.8% for the two species, respectively. Electronic cell counts were highly linear between 5 X 10(6) and 5 X 10(4) CFU/ml (R2 greater than 0.99). Multiple electronic counts of a single suspension of C. albicans had less variation than did multiple quantitative cultures of a suspension of the same organism (coefficients of variation, 2.4 versus 8.9%; P less than 0.01), suggesting that impedance counting is probably more precise than quantitative culture. Electronic particle counters can be used to prepare accurate, reproducible yeast inocula. The method may be more accurate and is more precise than other techniques commonly used to standardize yeast suspensions. PMID- 2584390 TI - Potentiation of antibody responsiveness after the transplantation of a syngeneic pituitary gland. AB - Transplantation of a pituitary graft under the kidney capsule and the resulting elevation of serum prolactin enhances the primary humoral antibody response to sheep red blood cells. Enhancement of the response is not due to marked changes in the percentage of T-cells and their subsets, B-cells, or the number of nucleated spleen cells. Quantitation of serum prolactin levels correlates well with the proportion of enhancement as mice with two grafts and higher levels of prolactin have increased responsiveness compared to mice with one graft. Systemic administration of mouse prolactin at the time of immunization also enhances the humoral immune response; however, if prolactin treatment is delayed and given 24 h after immunization, no potentiation of the response occurs. Thus, prolactin is enhancing the immune response by affecting an early afferent event in the induction of the immune response. PMID- 2584391 TI - Effector cells of autoimmune encephalomyelitis in the rat belong to the CD4 positive, OX22-adherent T cell subset. AB - We characterized the effector cells which mediate experimental autoimmune encephalomyelitis (EAE) on the basis of selective adherence properties. Nylon nonadherent spleen cells (SpC) from Lewis rats challenged earlier with myelin basic protein (BP) in adjuvant were separated by 'panning' on Petri dishes coated with monoclonal antibody (MAb) OX22. OX22 recognizes high molecular weight forms of the leukocyte-common antigen which is present on several cell types, including the CD4-positive T cells which mediate delayed hypersensitivity reactions. We found that the EAE effector cells were enriched in the OX22-adherent T cell population, which supports the hypothesis that delayed hypersensitivity is important in the pathogenesis of this autoimmune disease. PMID- 2584392 TI - Comparison and quantitation of Ia antigen expression on cultured macroglia and ameboid microglia from Lewis rat cerebral cortex: analyses and implications. AB - We isolated two subclasses of astrocytes, oligodendrocytes and ameboid microglia from Lewis rat cerebral cortex and analyzed Ia antigen expression on each glial cell type by immunofluorescent microscopy and cytofluorometry. All of these expressed little or no Ia without interferon-gamma (IFN-gamma) treatment. Following IFN-gamma treatment, Ia expression was observed on a majority (approximately 80%) of ameboid microglia, on half (approximately 55%) of the type 1 astrocytes, on a small number (approximately 7%) of type 2 astrocytes, but not on oligodendrocytes. These findings suggest that the type 1 astrocyte and microglia may play more predominant roles in Ia-related, immune-mediated intracerebral lesions although the type 2 astrocytes may also be involved. PMID- 2584393 TI - Anti-GM1 ganglioside antibodies with differing fine specificities in patients with multifocal motor neuropathy. AB - Antibodies to gangliosides were detected in sera from three of 19 patients with chronic inflammatory polyneuropathy (CIP) by a thin-layer chromatogram overlay technique. All three of the patients fell into a clinical subset of the group that had multifocal motor neuropathy, and in all three patients the antibodies reacted with GM1 ganglioside. However, the fine specificities of the antibodies differed as demonstrated by cross-reactivity with different gangliosides in each of the three patients. The antibodies in patient 1 reacted with GM1, GD1b, and asialo-GM1 suggesting that the terminal Gal(beta 1-3)GalNAc moiety that is common to these three glycolipids is an important part of the epitope(s). This was confirmed by showing reactivity of the antibodies with Gal(beta 1-3)GalNAc conjugated to bovine serum albumin. Patient 2 had antibodies that did not react with GD1b, but cross-reacted with GM2 ganglioside suggesting that the epitope(s) involved the inner portion of the oligosaccharide moiety that is shared between GM1 and GM2. Patient 3 had antibodies that reacted with GM1 and asialo-GM1, but they did not cross-react with either GD1b or GM2. These results provide further evidence for a relationship between motor nerve syndromes and anti-GM1 antibodies and also suggest that GM1 could be a principal target antigen since other reactive gangliosides differed among the patients. However, the possible pathogenic effects of anti-GM1 antibodies on motor nerves remain to be established. PMID- 2584394 TI - Monoclonal antibody analysis of major histocompatibility complex expression in human meningiomas. AB - Using monoclonal antibodies (MAB) in combination with the alkaline phosphatase anti-alkaline phosphatase technique, 20 meningiomas were examined for the expression of major histocompatibility complex (MHC) antigens. Most of the tumor cells were labeled with the MAB for class I MHC antigens. In addition, class I reactivity was seen in the tumor blood vessels, presumably reflecting labeling of the endothelial cells. Tumor cells and endothelium were not labeled with the MAB for class II MHC antigen HLA-DR. Occasionally a staining of periendothelial cells was detected. The presence of MHC antigens supports the assumption that endothelial cells play a role in antigen presentation, perhaps relevant to the initiation of an immune response, and that meningioma cells can be a target of T cell-mediated immune reactions. PMID- 2584395 TI - A quantitative immunocytochemical study of the infiltrating lymphocytes in the spinal cord of guinea pigs with chronic relapsing experimental allergic encephalomyelitis. AB - The production and characterization of an anti-guinea pig B cell monoclonal antibody is described. Immunocytochemical techniques using this antibody and others recognizing a Pan T cell antigen and T cell subsets were employed to study frozen sections of spinal cord from guinea pigs with chronic relapsing experimental allergic encephalomyelitis. T and B cells were found in both perivascular lesions and the central nervous system parenchyma, with the major T cell infiltration occurring by the end of the acute phase of disease. The distribution of T cell subsets suggests a phenotypic selectivity in favour of the transport of CT6 (putative CD8)+ve cells across the blood-brain barrier. PMID- 2584396 TI - Role of cervical lymph nodes in the systemic humoral immune response to human serum albumin microinfused into rat cerebrospinal fluid. AB - The humoral immune response to human serum albumin (HSA) microinfused into cerebrospinal fluid (CSF) has been measured in serum, cervical lymph nodes, and spleen of Sprague-Dawley rats. Conditions were designed to promote normal brain barrier function. Serum titers of anti-HSA antibodies, primarily IgG, increased over 10 days and then persisted for at least 10 weeks. A significant role for cervical lymphatics in the systemic response to CSF-administered HSA is suggested, based on results showing that (1) cervical lymph obstruction reduces serum titers of anti-HSA antibodies, and (2) total antibody production by combined superficial and deep cervical nodes, sampled 14 days post-immunization, exceeds that by the spleen. PMID- 2584397 TI - Activated T lymphocytes in cerebrospinal fluid of patients with HTLV-I-associated myelopathy (HAM/TSP). AB - In order to detect activated T lymphocytes in the cerebrospinal fluid (CSF) of patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we studied CSF lymphocytes in untreated patients with HAM/TSP and other neurological diseases (OND). Dual immunofluorescence staining technique was performed using fluorescence microscopy. No significant difference in the CD4+/CD8+ ratio of CSF lymphocytes was observed between HAM/TSP patients and patients with OND. However, both CD4+ and CD8+ CSF lymphocytes of HAM/TSP patients contained higher percentages of HLA DR-positive cells than those of patients with OND (P less than 0.05), suggesting that the activated CSF T lymphocytes were composed of both CD4+ and CD8+ subsets in patients with HAM/TSP. PMID- 2584398 TI - Measurement and significance of antibodies against GM1 ganglioside. Report of a workshop, 18 April 1989, Chicago, IL, U.S.A. AB - Twelve laboratories from the United States, Canada, France, Italy and Switzerland participated in a workshop to compare assays used to measure anti-GM1 antibodies, and to discuss the clinical significance of these antibodies. A panel of test samples containing varying amounts of anti-GM1 antibody was prepared by mixing varied proportions of normal serum with a serum containing a monoclonal IgM antibody that bound GM1 ganglioside. Enzyme-linked immunosorbent assay (ELISA) data were supplied by eight laboratories and ten laboratories classified the sera as negative, weakly or strongly positive. Most laboratories correctly identified the two samples that contained the highest quantities of antibody, but there was considerable disagreement on the classification of the three samples with moderate or small amounts of antibody. The sensitivity of the assays varied considerably. The more sensitive assays did not use detergent in the washing buffers, and incubated the human serum with the antigen at 4 degrees C overnight. Several investigators have identified a subset of patients with lower motor neuron disease or multifocal neuropathy who have high titers of anti-GM1 antibodies. Many patients with neurological and non-neurological diseases have low to moderate levels of anti-GM1 antibodies, and the significance of these antibodies is unclear. There was general agreement that standardization of the ELISA assays is urgently required, and that distribution of a reference high titered antiserum would facilitate this process. PMID- 2584399 TI - Classical conditioning of meaning--I. A replication and higher-order extension. AB - The meaning that individuals associate with verbal stimuli may be modified by using classical conditioning procedures. Clinically, such procedures may be used to modify a client's maladaptive associations. The current research investigated the existence and generalizability of this phenomenon by attempting to replicate Staats and Staats' (1957) language conditioning effect and then extent it to a second-order classical conditioning situation (CS1----UCS then CS2----CS1). Such higher-order conditioning would suggest that several different but related maladaptive associations can be modified simultaneously. Significant conditioning was obtained to the CS1, particularly for aware subjects, but no conditioning occurred to the CS2. PMID- 2584400 TI - A guide for conducting a comprehensive behavioral analysis of a target behavior. AB - This paper provides a sequenced, structured format for conducting a behavioral analysis. It is designed to help ensure that the analysis is comprehensive, that it includes potentially important antecedent events, that influencing factors become apparent and that useful recommendations for treatment can be derived from it. In addition, the guide solicits other useful types of information, including: (1) covert antecedents such as thoughts; (2) distant antecedents which may relate to a behavior; and (3) under what conditions the behavior does not occur. PMID- 2584401 TI - The reduction of bruxism using contingent EMG audible biofeedback: a case study. AB - This report describes the use of EMG biofeedback to reduce bruxism in an 18-year old woman. The behaviour was severe and not responsive to standard dental treatment. In addition to psychometric measures of affective status, objective measures of both the frequency and intensity of bruxing incidents were made, and a 4-week intervention conducted. On the bruxing and affective measures significant improvements were noted, as were reductions in associated pain and dysfunction. PMID- 2584402 TI - Use of immunochemistry in Britain: EQA forum antibody usage questionnaire. AB - A questionnaire was prepared under the auspices of the Department of Health with the aim of defining the extent and nature of immunocytochemistry use within pathology departments. The questionnaire was circulated to 320 pathology laboratories within the United Kingdom, and a total of 178 replies were received, representing a response rate of 56%. One hundred and thirty eight (78%) of the respondents used immunocytochemical techniques: 64 used immunocytochemical kits, including 35 district general hospital and 29 teaching hospital laboratories. An extensive range of antibodies was being used on a variety of tissues, epithelial and lymphoid markers far exceeding all other antibodies. Several differences in the numbers of cases and the types of tissues studied were identified among laboratories. The techniques used, the problems encountered, and the procedures followed with unsatisfactory reagents were also analysed. Finally, an assessment of the resources allocated to immunocytochemistry, both in terms of staff and reagent costs was made. Taking into account the response rate of 56% and the uncertainty that all pathology departments in the United Kingdom had been circulated, the estimated annual total costs for immunocytochemistry for all pathology laboratories in the United Kingdom was 5.4 million pounds. PMID- 2584403 TI - Bronchial gland duct ectasia in fatal bronchial asthma: association with interstitial emphysema. AB - To determine the incidence of bronchial gland duct ectasia in fatal asthma and its association with interstitial emphysema, the histological features of 72 patients in whom death was considered to be due to asthma, and 72 matched control subjects in whom sudden death was not attributed to asthma, were reviewed. In all cases and controls, sections of two or more blocks of lung tissue stained with haematoxylin and eosin were obtained at necropsy. Bronchial gland duct ectasia was diagnosed if there was more than one abnormally dilated epithelial lined protrusion from a bronchus, extending through the smooth muscle layer. A histological diagnosis of asthma was made if four of the five following criteria were present: mucus plugging, basement membrane thickening, epithelial shedding, submucosal eosinophil leucocyte infiltration and smooth muscle hypertrophy. A histological diagnosis of asthma was made in 53 of 72 clinical cases of fatal asthma and in five of 72 control subjects. Interstitial emphysema was present in 10 clinical cases of fatal asthma, all of whom had bronchial gland duct ectasia and a histological diagnosis of asthma. Interstitial emphysema was not observed in control subjects. It is concluded that bronchial gland duct ectasia is a common histological feature of severe asthma, and that interstitial emphysema may be consequent on rupture of these dilated gland ducts. PMID- 2584404 TI - Is there any justification for the routine examination of bowel resection margins in colorectal adenocarcinoma? AB - The proximal and distal bowel resection margins of 339 specimens of colorectal adenocarcinoma were examined for the presence of tumour. In only five cases was tumour found in a resection margin. In four of these cases macroscopic examination showed that the tumour extended to the resection margin. In the fifth case the tumour was present in the pericolic fat. These results and reported data on the intramural spread of colorectal cancer suggest that examination of bowel resection margins is unnecessary unless the tumour extends to within 2 cm of the resection margin. Examination of the deep radial margins of the tumour and slides to show other prognostic indicators would be a more effective use of histopathological resources. PMID- 2584405 TI - Prognostic value of prostaglandin F2 alpha concentrations in breast carcinoma. AB - Prostaglandin F2 alpha (PGF2 alpha) concentrations were measured by radioimmunoassay in homogenised primary tumours from 57 patients with breast cancer. These patients were followed up from 60 to 78 months (median 63 months) after surgery and PGF2 alpha concentrations were related prospectively to metastatic spread and survival. The amounts of PGF2 alpha varied greatly in the different tumours (range 0-90 ng/mg protein), but no significant association was found between PGF2 alpha concentrations and disease free survival, time of relapse, site of recurrence, or overall survival. It therefore seems unlikely that measurement of PGF2 alpha in breast carcinoma is important in the prognosis of the disease. PMID- 2584407 TI - Immunolocalization of alpha interferon in liver disease. AB - The expression of immunoreactive alpha interferon was examined in 78 liver biopsy specimens using an indirect immunoperoxidase technique. Biopsy specimens included cases of acute viral hepatitis, chronic active hepatitis, primary biliary cirrhosis, alcoholic hepatitis, large bile duct obstruction and normal liver. Kupffer cells were positive for alpha interferon in all cases. Hepatocytes were negative for alpha interferon in normal liver but in acute viral hepatitis were positive in perivenular and necrotic areas. Hepatocytes were positive in periportal areas, associated with piecemeal necrosis, in chronic active hepatitis and primary biliary cirrhosis, and were positive in perivenular areas in alcoholic hepatitis and large bile duct obstruction. The unexpected finding of alpha interferon in hepatocytes in non-viral liver disease indicates that the presence of this substance in liver cells cannot be taken as a specific marker of viral infection. PMID- 2584406 TI - Findings in lymph nodes of patients with germ cell tumours after chemotherapy and their relation to prognosis. AB - One hundred and forty six patients with advanced germ cell testicular tumours (38 seminomas and 108 malignant teratomas) treated by combination chemotherapy were studied over 10 years. Most of the improvement seen was in patients with malignant teratoma undifferentiated. In the most recently treated patients (1984 1987) 75% of drug resistant cases were malignant teratoma intermediate compared with 26% in the series treated between 1978-1983. The microscopic features of 52 primary testicular tumours were compared with features seen in excised retroperitoneal lymph nodes after completion of chemotherapy. Primary malignant teratoma intermediate had a higher incidence of viable malignancy in the excised tissue than malignant teratoma undifferentiated. Mature teratoma or fibronecrotic tissue within resected tissue was associated with a good prognosis. If resection was complete patients with drug resistant malignant teratoma intermediate had a more favourable prognosis than drug resistant malignant teratoma undifferentiated. It is advised that retroperitoneal node dissection should be considered in the management of patients with advanced germ cell testicular tumours, and that as complete a resection as possible be attempted to avoid the danger of missing residual disease. PMID- 2584408 TI - Leucocyte behaviour in controlled ischaemia of the calves. AB - Whole blood filterability and leucocyte behaviour (number, activation, and subfraction filterability rates) were monitored at the earliest stage of peripheral ischaemia in 18 patients with stage II peripheral occlusive arterial disease (PAOD) and 20 matched controls. A model of controlled ischaemia, using exercise to stress leg circulation, was set up and blood samples were taken before exercise, at the onset of calf pain, and at recovery from peak exercise. Leucocytes were counted, separated into their subfractions on a Ficoll-Hypaque density gradient and by adhesion to Petri dishes, and filtered in buffer (like the whole blood suspensions) through 5 microns pore diameter Nucleopore filters. Unfractionated white cells, separated under gravity, with pseudopodia or cytoplasmic irregularities were regarded as activated. The whole blood filterability rate was significantly increased at the onset of calf pain and was associated with significant increases in the number of leucocytes and in the filterability rate of the monocyte subfraction, the latter persisting throughout the recovery period. No significant changes were observed in the other variables monitored, showing that impairments in white cell rheology may be associated with ischaemia. PMID- 2584409 TI - Erythrocyte autoantibodies, autoimmune haemolysis, and myelodysplastic syndromes. AB - Immunohaematological investigations were carried out in 46 patients with erythrocyte autoantibodies associated with myelodysplastic syndromes. Eight patients had refractory anaemia, 17 refractory anaemia with ring sideroblasts, 11 refractory anaemia with excess of blasts, four chronic myelomonocytic leukaemia, five refractory anaemia with excess of blasts in transformation and one could not be classified. Standard agglutination direct antiglobulin tests showed that the red cells were most often coated with IgG and C3d, though increased amounts of IgM or IgA were also found in 15 of 35 cases (43%) when the more sensitive enzyme linked method was used. The IgG antibodies were predominantly of IgG1 subclass. Clinically important autoimmune haemolysis occurred in 15 patients, and was of "warm", "cold," and "mixed" types in seven, four, and four cases, respectively: it is important to recognise its presence in view of the good response to treatment. The increased incidence of erythrocyte autoantibodies in myelodysplastic syndromes is thought to be one manifestation of disturbed immune homeostasis. PMID- 2584410 TI - Longitudinal study of circulating gastric antibodies in pernicious anaemia. AB - Temporal changes in gastric antibody response were investigated in 113 (51 men, 62 women) patients with confirmed pernicious anaemia. Their ages ranged from 31 92 years (mean (SD 13.2) 66). At diagnosis, parietal cell antibody and intrinsic factor antibody were detected in 90.9% and 39.1% of all patients, respectively. When the tests were repeated after a mean follow up of 70 months (range 14-137), parietal cell antibody and intrinsic factor antibody were positive in 82.8% and 58.7%, respectively. There was a definite but not significant trend for the organ specific parietal cell antibody to disappear; intrinsic factor antibody became more positive. These results may indicate that with progressive parietal cell destruction, the antigen is no longer available to sustain an immunological response. On the other hand, this hypothesis does not explain the increased prevalence of intrinsic factor antibody which is also a product of parietal cells. PMID- 2584411 TI - New method for preserving cytology specimens. AB - A method of freezing cytological material for long term storage, based on a modification of that used in tissue typing for the storage of lymphocytes, was developed. The method entails the centrifugation of the specimen, adding 1 ml AB or fetal calf serum and 1 ml 20% dimethyl sulphoxide aliquoted into 2 ml tubes, and storage at -70 degrees C. Cytological detail was well preserved in a variety of samples including fine needle aspirates, urine, and bronchial brushings. Three dimensional architecture was also preserved. The method is practical, easy to perform, and allows retrospective studies to be undertaken with the subsequent use of a variety of special staining techniques, including immunocytochemistry. PMID- 2584413 TI - Campylobacter-like organisms in Meckel's diverticulum? PMID- 2584412 TI - Light and electron microscopic demonstration of extracellular immunoglobulin deposition in renal tissue. AB - Extracellular immunoglobulin (IgG) deposits were shown by both light and electron microscopy in renal biopsy material using immunogold labelling. After fixation of tissue in 4% paraformaldehyde and embedding in Lowicryl K4M, semithin sections were cut and stained using the immunogold silver stain. The sections were then viewed and areas of interest were noted; ultrathin sections were cut from the same block of tissue, then stained using immunogold. Good localisation was achieved at both optical and ultrastructural levels allowing direct correlation to be made in the same area of tissue. PMID- 2584414 TI - Duodenal gastric heterotopia and Campylobacter pylori: an exception to the rule? PMID- 2584415 TI - Infiltrative myeloid metaplasia: an unusual cause of gastric outlet obstruction. PMID- 2584416 TI - Effect of penicillin on endocarditis strains of viridans streptococci. PMID- 2584417 TI - Limulus amoebocyte lysate (LAL) assay and rapid detection of gram negative bacterial peritonitis in patients receiving CAPD. PMID- 2584418 TI - Effect of heat inactivation of sera on anti-Trichomonas vaginalis IgG ELISA. PMID- 2584419 TI - Manual and automated prothrombin time tests. PMID- 2584420 TI - Morphometric analysis of suprabasal cells in oral white lesions. PMID- 2584421 TI - ISI value of thromboplastin. PMID- 2584422 TI - Diagnosis of acute myocardial infarction from sequential enzyme measurements obtained within 12 hours of admission to hospital. AB - A prospective study was made of sequential changes in serum creatine kinase (CK) and CK-MB isoenzyme activity within the 12 hours following admission to the coronary care unit on 65 patients with recent chest pain. CK determinations were performed in the laboratory or in the coronary care unit using a dry reagent strip analyser. Slope values for log CK/hour and log CK-MB/hour were calculated, used to confirm or exclude the diagnosis of myocardial infarction, and compared with diagnosis by conventional means. Compared with retrospective diagnosis using all available information, the CK slope had a sensitivity of 100% and a specificity of 94%. This compared with a sensitivity of 94% and specificity of 90% for diagnosis using upper reference limits alone. Determination of CK slope permits very rapid and accurate biochemical confirmation or exclusion of myocardial infarction and the possibility of performing the measurements on the coronary care unit. It additionally offers the prospect of major cost savings resulting from early discharge or transfer from the coronary care unit. PMID- 2584423 TI - Is low proteinuria an early predictor of severity of acute pancreatitis? AB - Serial six hourly urine collections were made for seven days on 20 patients with acute pancreatitis. Quantitative immunoassay of urinary albumin and IgG on the first urine sample after admission showed increased excretion rates in 14 and 13 patients, respectively. Urinary protein excretion rates remained normal or approached normal by seven days in 17 patients who made uneventful recoveries. The maximum urinary excretion rates of both albumin and IgG within the first 36 hours correlated with the serum C-reactive protein concentration 72 hours after admission. The highest IgG excretion rates were found in three patients who later developed severe complications. These preliminary data suggest that low proteinuria is a very early response in acute pancreatitis, and that it may reflect the severity of inflammation. PMID- 2584424 TI - Microbiology of infected pilonidal sinuses. AB - Aspirates of pus from infected pilonidal sinuses in 75 patients showed bacterial growth. Anaerobic bacteria only were recovered in 58 (77%) specimens, aerobic bacteria only in three (4%), and mixed aerobic and anaerobic bacteria in 14 (19%). Two hundred and nine isolates were recovered: 147 anaerobes (2.0 isolates a specimen) and 62 aerobes (0.8 a specimen). The predominant anaerobes were Bacteroides sp (81 isolates, including 29 Bacteroides fragilis group) and 51 anaerobic cocci. The predominant aerobes were Escherichia coli (n = 15), Proteus sp (n = 9), group D streptococcus (n = 7), and Pseudomonas sp (n = 7). This study highlights the polymicrobial nature and predominance of anaerobic bacteria in infected pilonidal sinuses. PMID- 2584425 TI - Changes in phagocytic function with glycaemic control in diabetic patients. AB - Phagocytic function was assessed by serial whole blood chemiluminescence in poorly controlled type 2 (non-insulin dependent) diabetic patients during efforts to improve glycaemic control and compared with a group of well controlled type 1 (insulin dependent) diabetic patients. Chemiluminescence (corrected to a standard polymorphonuclear count) remained below normal (0.15-0.30 photons/second/cell) for most of the type 2 patients until 12 weeks when the value was significantly increased in patients showing improved glycaemic control (mean (range) 0.25 (0.01 0.43) photons/second/cell) compared with those showing no improvement (0.12(0.01 0.31) photons/second/cell). There was a significant inverse correlation of delta HbA1 with delta chemiluminescence. Although mean chemiluminescence for the type 1 diabetic patients was within the normal range, there was a wide scatter of values (0.19 (0.04-0.43) photons/second/cell) and there was no significant difference compared with the final value of type 2 patients with improved control. Glycaemic control is therefore a major determinant of phagocytic function in diabetic patients, but other factors must contribute, particularly in type 1 (insulin dependent) patients. PMID- 2584426 TI - N-myc amplification in neuroblastomas: histopathological, DNA ploidy, and clinical variables. AB - The association between tumour N-myc amplification, DNA ploidy, and various prognostic factors (patient age, tumour stage at diagnosis, primary site and histopathological differentiation) was studied in 18 children who had neuroblastoma, ganglioneuroblastoma, or ganglioneuroma. Amplification of genomic N-myc was observed in six patients who had been treated with chemotherapy before surgery (one with stage III and five with stage IV). All these tumours were located in the adrenal or upper retroperitoneum; five were neuroblastomas and one was a ganglioneuroblastoma. Three of them were aneuploid and three diploid. The degree of N-myc patients with tumour N-amplification varied from 20 to 1500 copies without relation to ploidy. All patients with tumour N-myc amplification died of their tumour. Amplification was always associated with poor prognosis, independent of tumour cell ploidy. Four patients without such amplification also died: three had diploid tumours, the fourth was aneuploid. It is suggested that genomic N-myc amplification takes place mainly in adrenal and retroperitoneal neuroblastomas and can be a feature of tumours with and without histological signs of differentiation. The precise role of N-myc in the pathogenesis of neuroblastoma remains unclear. PMID- 2584427 TI - Brown adipose tissue activity in pyrexial cases of cot death. AB - Brown adipose tissue was investigated in two cases of cot death in which core temperatures were above 40 degrees C on arrival at the mortuary. Evidence was obtained from mitochondrial (8-3H) guanosine diphosphate (GDP) binding and oxygen uptake of active thermogenesis with uncoupled mitochondrial respiration which was recoupled by GDP. Thermogenic capacity of brown adipose tissue, estimated by radioimmunoassay of the specific mitochondrial membrane "uncoupling protein" responsible for heat production, was similar to that measured in other infants or in experimental animals acclimated to moderately warm conditions (23 degrees C). Brown adipose tissue thermogenesis, occurring inappropriately in a warm, well insulated infant, could be a cause of some cases of cot death. PMID- 2584428 TI - Umbilical cord sclerosis as an indicator of congenital syphilis. AB - In two cases of congenital syphilis examination of the umbilical cord showed a distinctive picture of perivascular sclerosis and inflammation. Large numbers of spirochaetes were shown in the sclerotic zone in both cases. No organisms were demonstrable in the placental disc and there were no morphological changes suggestive of syphilis. It is concluded that the finding of sclerosing funisitis, together with the clinical circumstances, should raise the possibility of congenital syphilis. PMID- 2584429 TI - Portal lymphadenopathy associated with lipofuscin in chronic cholestatic liver disease. AB - To determine whether portal lymphadenopathy in primary biliary cirrhosis is caused by deposition of lipofuscin pigment in sinus histiocytes and to compare primary biliary cirrhosis with other liver diseases a retrospective study on a consecutive series of 169 livers obtained at transplantation was carried out. There were grouped into eight diagnostic categories: primary biliary cirrhosis (n = 51), primary sclerosing cholangitis (n = 10), extrahepatic biliary atresia (n = 6), chronic rejection (n = 9), cirrhosis (other causes) (n = 38), primary liver neoplasia (n = 21), acute liver disease (n = 20), and retransplantation (other) (n = 14). Lymph nodes were present in 66 specimens. Fifty of these contained granules of lipofuscin pigment. The highest incidence of lymph node enlargement and the largest amounts of pigment were present in cases of primary biliary cirrhosis. A similar pattern of lymph node enlargement was also commonly observed in other chronic cholestatic conditions (primary sclerosing cholangitis, biliary atresia, chronic rejection). Much less pigment was seen in nodes draining livers with non-cholestatic cirrhosis or primary tumours. Nodes were not found in acute liver disease. It is concluded that portal lymphadenopathy associated with lipofuscin is a common finding in various chronic cholestatic liver diseases. The pathogenesis of this lesion is uncertain. Most cases are asymptomatic with enlarged nodes which may be detected only at laperotomy or necropsy and may be wrongly attributed to neoplastic disease. Diagnostically, the finding of large amounts of lipofuscin in enlarged portal lymph nodes is a good indicator of underlying chronic cholestatic liver disease. PMID- 2584430 TI - Breast carcinoma cellularity and its relation to oestrogen receptor content. AB - The cellularity of 104 primary breast carcinomata was determined by semiautomated image analysis to allow the relation between cellularity and oestrogen receptor content values to be assessed. The oestrogen receptor content of tumours detected by a steroid binding assay showed no correlation with cellularity, although a possible weak negative correlation was observed between tumour cellularity and oestrogen receptor content detected by enzyme immunoassay. It is concluded that there is no single direct correlation between tumour cellularity and oestrogen receptor content. PMID- 2584432 TI - Quality assurance programme for necropsies. AB - One hundred and eight consecutive necropsies were entered into a quality assessment of the necropsy service in this hospital using a previously published American protocol. Our results were similar to those of the American series, with confirmation of the major clinical diagnosis in 75%, but a higher rate of unsuspected diagnosis (44%). Necropsy was helpful in 58% of cases. The presentation of selected cases at a monthly conference on causes of death was valuable in correlating clinical and pathological findings, and in helping integrate both services. PMID- 2584431 TI - Pathology of tropical appendicitis. AB - Over the past 25 years, 2921 appendicectomies were performed at this hospital. All were subjected to routine histopathological examination. In 95% of cases, histopathological examination did not add any further information but in 153 (5%) cases, clinically important pathological findings were detected for the first time. Seventy (2.3%) specimens showed typical evidence of tuberculosis. Parasitic infestation was detected in 75 (2.5%), including enterobiasis (1.4%), amoebiasis (0.5%), ascariasis (0.5%), ascariasis with trichuriasis (0.05%), and taeniasis (0.05%). Other lesions found were mucocele (0.1%) and carcinoid tumour (0.1%). It is concluded that routine histopathological examination of all appendicectomy specimens should be performed to avoid missing any clinically important and treatable condition. PMID- 2584433 TI - Detection of hepatitis B virus DNA in serum using synthetic non-radioactive oligonucleotides. AB - A rapid and simplified technique for detecting hepatitis B virus (HBV) DNA by spot hybridisation in the sera of patients with different clinical forms of HBV infection was investigated using enzyme conjugated synthetic oligodeoxyribonucleotides as probes. These are able to hybridize to the S and C regions of the HBV L(-) DNA strand. When compared with a complete 32P-labelled HBV DNA probe, the synthetic oligonucleotides provided a sensitive and quick method for the routine survey of HBV infection. Moreover, the DNA extraction procedure used allowed the spot hybridisation technique to be applied and read easily and the results obtained within a few hours. It is concluded that synthetic cold probes can be used in hybridisation assays HBV DNA detection as part of current clinical laboratory procedures. PMID- 2584434 TI - Breast carcinoma metastatic to the gallbladder. PMID- 2584435 TI - Respiratory syncytial virus pneumonia. PMID- 2584436 TI - DNA aneuploidy in sarcoid granuloma. PMID- 2584437 TI - Barium sulphate radio-opacity agent and bacterial adhesion to silicone catheter material. PMID- 2584438 TI - Hypothyroidism: an important differential diagnosis for raised serum transaminases? PMID- 2584439 TI - Use of necropsy in clinical audit. PMID- 2584440 TI - Clinical importance of squamous metaplasia in invasive transitional cell carcinoma of the bladder. PMID- 2584441 TI - Hodgkin's disease presenting with hypercalcaemia. PMID- 2584442 TI - Value of throat swabs in meningococcal meningitis. PMID- 2584443 TI - Studies on cardiovascular fluke (Digenea: Spirorchiidae) infections in sea turtles from the Great Barrier Reef, Queensland, Australia. AB - Twenty-seven sea turtles (23 Chelonia mydas and four Eretmochelys imbricata) from northeast Queensland were found to be infected with cardiovascular flukes and/or their eggs. Five had originated from turtle farms in the Torres Strait, five from an oceanarium on Magnetic Island (146 degrees 56'E, 19 degrees S) and the remainder from coral reefs in the Torres Strait or near Townsville. The incidence of flukes and/or eggs in the groups was 4.8 per cent (5 of 104), 33.3 per cent (5 of 15) and 72.2 per cent (17 of 22), respectively. Affected animals ranged in size from 18 to 108 cm (curved carapace length) and weighed between 0.5 and 77 kg. The average number of flukes per host was 47. Flukes were recovered from the three chambers of the heart and major vessels (right aortic arch and brachiocephalic artery), where they were attached to the walls or free in the lumen. They were subsequently identified as Haplotrema spp. and/or Learedius spp. In 59.2 per cent (16 of 27) of turtles, flukes were not found, although their eggs were detected microscopically. Gross pathological changes associated with the presence of flukes included thickening and hardening of arterial walls (four turtles), thrombus formation (three), chronic pneumonia (two) and an excess of pericardial or peritoneal fluid (four). Microscopically, the essential changes was that of chronic inflammation, as evidenced by the proliferation of epithelial cells, reticulo-endothelial cells and fibroblasts in areas accessible to flukes and/or eggs. Multiple diffuse egg granulomas were a prominent feature of most organs, the spleen and lungs being predilection sites. Proliferative changes had occurred in the endocardium and in the endothelium of vessels supplying the spleen, stomach, intestine and pancreas (18 turtles). The walls of major arteries, lungs, liver, brain, crop and stomach were also acutely inflamed (eight turtles). Haemorrhage was recorded in the lungs and/or brain of eight turtles with heavy fluke infestations. Other vascular changes, viz. congestion, oedema and hypertrophy of arterial/arteriolar walls, resulted from the inhibition of blood flow by parasitic emboli. PMID- 2584444 TI - The ultrastructural pathology of five lipoprotein lipase-deficient cats. AB - The ultrastructural pathology of cats suffering from familial lipoprotein lipase deficiency is described. There were large numbers of lipid vacuoles within hepatocytes, epithelial cells of the proximal convoluted tubule of kidney and macrophages of the liver, spleen and lymph node. The older cats tended to have larger quantities of ceroid within hepatocytes and macrophages, and all stages of development of ceroid were observed. Chylomicron emboli were seen within the glomerular capillaries and interlobular blood vessels. There was podocyte foot fusion and thickening of basement membranes of glomeruli, Bowman's capsule and some proximal convoluted tubules, similar to that seen in diabetes mellitus. These changes represent a non-specific reaction of the kidney to noxious insults such as hypoxia caused by emboli. Transformation of smooth muscle cells from a contractile to a synthetic state was seen in the splenic trabeculae and, to a lesser extent, in blood vessels. Dilatations of the nuclear membrane of the lymphocytes were noted, the significance of which is unknown. PMID- 2584445 TI - Polyglucosan bodies in the brain of the cat. AB - Polyglucosan bodies (PGB) were examined by light and electron microscopy in the brain of cats without neurological signs. PGB in the feline brain were round, basophilic, PAS-positive, filamentous structures. Both morphologically and histochemically, PGB in the cat were identical to Lafora bodies and similar structures found in man and other animals. Most of the bodies were situated in the neuronal processes, but were not found in perikarya. PGB were disseminated throughout the brain, especially in the cerebral cortex, midbrain, cerebellum and medulla oblongata. The occurrence of PGB in the feline brain may represent an ageing phenomenon. PMID- 2584446 TI - Investigations of bone marrow dyscrasia in a poodle with macrocytosis. AB - A poodle-type dog with bone marrow dyscrasia and macrocytosis was investigated by clinicopathological, cytological and ultrastructural means. Peripheral blood analysis revealed macrocytosis and the presence of nucleated erythroid cells, some with nuclear/cytoplasmic asynchrony. Tendencies towards neutropenia and granulocytic hypersegmentation were observed. Bone marrow examination revealed low normal myeloid to erythroid ratio, the presence of megaloblasts and some giant metamyelocytes. In addition, there were abnormal mitoses, binuclearity and multinuclearity, incomplete nuclear membranes and nuclear clefts, intracytoplasmic parallel-sided membranes and apparent degenerate erythroid cells. Blood biochemical tests indicated normal to high concentrations of serum vitamin B12, serum folate and red cell folate. Transcobalamin I/IIIB12-binding capacity was similar to values for normal dogs, but transcobalamin II-binding capacity appeared high. It was concluded that the condition had similarities to both congenital dyserythropoietic disorders and true megaloblastic conditions, but until further investigations are reported it might be wise to refer to it as "bone marrow dyscrasia" in poodles. PMID- 2584447 TI - Arteriosclerosis and related lesions in rabbits. AB - Eleven female rabbits, mainly of the NZW breed, aged between 1 and 3.5 years, were examined post mortem. All had originated over the years 1982 to 1987 from the same rabbitry where they had been fed on pellets from the same manufacturer. Apart from one rabbit, all had a history of progressive loss of bodily condition and six of them had also been infertile. Grossly, most of them were emaciated and their arteries were hardened. In some, hepatopathy, nephropathy and pulmonary emphysema were evident. In one case, mummified foetuses were recovered from the abdominal cavity. Microscopically, degenerative changes and calcification were found in the walls of arteries, kidneys, lungs, hearts and ovaries. PMID- 2584448 TI - Spontaneous reproductive tract leiomyomas in aged guinea-pigs. AB - Seven of 83 female guinea-pigs were found to have reproductive tract leiomyomas at necropsy. Sixty-three of these guinea-pigs also had cystic rete ovarii. Eleven separate leiomyomas were identified, the most common site of formation being the uterine body or horn. The tumours contained histological evidence of smooth muscle, abundant fibrous connective tissue and occasional foci of fibrocartilage and bone. Mitotic figures were identified in only one tumour. The mean age of guinea-pigs with leiomyomas was 47.6 months, and the mean age of the study population was 33.1 months. Two other reproductive tract tumours identified in the 83 guinea-pigs were an ovarian teratoma and a cavernous haemangioma. These data indicate that leiomyomas are the most common reproductive tract tumour in this colony of aged female guinea-pigs and that they are frequently seen in conjunction with cystic rete ovarii. PMID- 2584449 TI - Experimental infection of eland (Taurotrages oryx), sable antelope (Ozanna grandicomis) and buffalo (Syncerus caffer) with foot-and-mouth disease virus. AB - The course of experimental infection of a type SAT 1 FMDV strain was studied in buffalo, sable antelope and eland following tongue inoculation and contact and has been compared with that in cattle. All species became infected, although disease was less severe in the game animals and larger amounts of virus were required to infect game animals than cattle. Neutralizing antibody titres were high and were maintained for an extended period in buffalo, sable antelope and eland. The carrier state was demonstrated in buffalo for the longest period. Cattle carried virus for up to 56 days. Virus persistence in sable antelope was transitory and did not occur in eland. PMID- 2584450 TI - Complications of a permanent transvenous pacing catheter in a horse. AB - Gross and histopathological findings in a 9-year-old horse implanted with permanent transvenous pacing cardiac catheters, 18 and 34 months before its death, are described. Lesions consisting of extensive fibrino-haemorrhagic thrombi with large numbers of bacterial colonies were present along the electrode wires and on mural and valvular endocardial surfaces of the right heart. There was a locally extensive area of suppurative endocarditis around the attachment site of the atrial electrode, which was loosely attached by a thin band of membranous tissue to the endocardium. The ventricular electrode was firmly embedded in the myocardium and was surrounded by a dense area of fibrous connective tissue in which multifocal mineralized areas were seen. Histologically, there was evidence of terminal bacteraemia. The observed lesions are discussed with respect to findings in man and other animals with similar cardiac implants. PMID- 2584452 TI - Argyrophilic, intracellular bacteria in some cats with idiopathic peripheral lymphadenopathy. AB - Lymph node biopsy specimens from several previously reported cases of unusual feline peripheral lymphadenopathies were re-examined by a modified Dieterle silver-impregnation staining technique. In a proportion of these specimens, the Dieterle stain revealed tiny pleomorphic, intensely argyrophilic coccobacilli. These organisms were predominantly located within macrophages. The infected cells were focally distributed, particularly in the interfollicular regions of the nodes. They were inconspicuous in sections stained by other, more conventional staining methods. It is possible that these coccobacilli represent yet another, previously unidentified, cause of chronic lymph node hyperplasia in the cat. PMID- 2584451 TI - Respiratory tract-associated lymphoid tissue in conventionally raised sheep. AB - The distribution and morphological features of respiratory tract-associated lymphoid tissue was investigated in 20 clinically healthy sheep aged from 6 months to 9 years. Five different forms of lymphoid tissue were identified, but their distribution varied between regions of the respiratory tract and between individuals. Scattered lymphoid cells were the most predominant form. Dense lymphoid aggregations were frequently seen in the pharyngeal tonsil and bronchioles. They were less common in the mid-nasopharynx and about the opening of the auditory tube, occasionally seen in the anterior nasopharynx, trachea and bronchus and rarely found in the regions of the nasal conchae, nostril, nasal vestibule and epiglottis. Nodular lymphoid aggregations with morphologically distinct lympho-epithelium were seen only in the pharyngeal tonsil and opening of the auditory tube region. Small numbers of intra-epithelial lymphoid cells were always present throughout the mucosa, but intraluminal lymphocytes were observed mainly in the regions of pharyngeal tonsil, trachea, bronchi and large bronchioles. The respiratory tract-associated lymphoid tissue is less developed in sheep than in most other species studied, except perhaps cattle. PMID- 2584453 TI - Naturally occurring mucocutaneous histoplasmosis in a rabbit. AB - Mucocutaneous histoplasmosis was diagnosed in a pet rabbit. A mass protruding through the anal opening was histologically composed of a densely cellular infiltrate of macrophages which expanded the anorectal submucosa. Macrophages contained abundant yeast forms of fungi morphologically consistent with Histoplasma capsulatum. Infection appeared to be localized. Histoplasmosis should be considered in the differential diagnosis of granulomatous inflammatory disease in the rabbit. PMID- 2584455 TI - Reproducibility of patch tests. AB - Patch tests with a series of 39 substances were performed in 41 patients on one side of the upper aspect of the back. Testing was repeated on the contralateral side of the back 1 week later (sequential testing). In 35 other patients, duplicate patch test series were simultaneously applied on both sides of the back (concomitant testing). If a positive reaction to a test substance was obtained at only one side of the back, the result was regarded as nonreproducible. Of all positive reactions, 40.0% were nonreproducible at sequential testing and 43.8% were nonreproducible at concomitant testing. Weakly positive reactions were far more often nonreproducible than stronger reactions. PMID- 2584454 TI - Disseminated superficial actinic porokeratosis: experimental induction and exacerbation of skin lesions. AB - A 55-year-old woman with disseminated superficial actinic porokeratosis (DSAP) had lesions on sun-exposed skin areas that were exacerbated during the summer months and involuted in winter. This is the third report in which induction and exacerbation of DSAP lesions were achieved by irradiation with artificial ultraviolet light sources. Our data show that UVB plus UVA is more effective in inducing new or exacerbating preexisting skin lesions than either wavelength alone. We believe that testing with the appropriate ultraviolet light sources is a practical means to differentiate between DSAP and disseminated superficial porokeratosis. PMID- 2584456 TI - Reactions to a bovine collagen implant. Clinical and immunologic study in 705 patients. AB - A small percentage of patients treated with bovine collagen implants have adverse reactions involving both the cellular and humoral types of immune response. We report a clinical follow-up of 705 subjects treated with a new bovine collagen implant, Atelocollagen (Koken Co. Ltd., Tokyo, Japan). Sensitization to the implant was evaluated in all subjects by skin testing, and humoral response was monitored in 166 subjects by measuring the level of circulating antibodies directed against bovine collagen. Twenty-seven patients (3.8%) exhibited a positive response to a skin test, and of the remaining 656 patients, an adverse reaction to the implant developed in 2.3%. We found a strong correlation between the presence of antibodies to collagen and a positive response to skin testing (92%) or an adverse reaction (100%). In the case of a borderline clinical response to bovine collagen implantation, anticollagen serologic tests appeared to be a useful tool for the identification of clinically reactive patients. PMID- 2584457 TI - Evaluation of the adult carrier state in juvenile tinea capitis caused by Trichophyton tonsurans. AB - The anthropophilic dermatophyte Trichophyton tonsurans is an occasional cause of scalp ringworm in adults. An asymptomatic adult carrier state also has been described. In this study the parents and/or grandparents of 50 children with proved T. tonsurans tinea capitis were evaluated. Cultures were obtained from the scalps of 46 asymptomatic adults; 14 of the cultures grew T. tonsurans. This population may provide a source for continued reinfection in children. PMID- 2584459 TI - Cutaneous sarcoidosis in Nigeria. AB - The study is a retrospective analysis of the cutaneous manifestations of sarcoidosis in patients seen during a 10-year period at the skin and chest clinics of the Lagos University Teaching Hospital. Of the 43 patients with sarcoidosis 30% had skin lesions. The most common was sarcoidal infiltration of scarification marks. Facial macropapular lesions also were frequently present. PMID- 2584458 TI - Annular erythema associated with primary Sjogren syndrome: analysis of T cell subsets in cutaneous infiltrates. AB - Immunohistochemical analysis was performed on the annular erythema associated with Sjogren syndrome. This type of annular erythema is characterized by a doughnutlike appearance with an elevated border and central pallor; it is distinct from subacute cutaneous lupus erythematosus. Histologically this erythema is characterized by coat sleeve-like infiltration of lymphocytes around blood vessels and by nuclear debris in the connective tissue. Vasculitis or epidermal changes suggestive of lupus erythematosus were not observed in any of the cases, although immunoglobulin or complement deposition along the basement membrane zone and focal liquefaction degeneration of the basal layer in involved skin were seen in some cases. Major dermal infiltrates consisted primarily of CD4+ and 4B4+ lymphocytes. PMID- 2584460 TI - Cutaneous mucormycosis. AB - We report two cases of primary cutaneous mucormycosis in immunocompromised patients. Although their clinical presentation showed nonspecific necrotic ulcers, the histopathologic features were diagnostic. In both cases, broad, branching, nonseptate hyphae were found in the dermis and subcutaneous tissue. In one case the hyphae could be observed in the epidermis. To our knowledge, this is the only reported case of primary cutaneous mucormycosis with hyphae detectable in the epidermis. PMID- 2584462 TI - Recurrent pyogenic granuloma with satellitosis. AB - The development of recurrent pyogenic granulomas as multiple satellite lesions is rare and often associated with trauma or treatment of the primary lesion. At least 34 cases of such lesions after various treatment modalities have been reported, but none occurred in conjunction with laser therapy. We report a case of recurrent pyogenic granuloma with satellite lesions that developed after carbon-dioxide laser excision of a previously recurrent lesion. PMID- 2584461 TI - Mucocutaneous complications of intraarterial 5-bromodeoxyuridine and radiation. AB - 5-Bromodeoxyuridine (BUDR), a halopyrimidine thymidine analogue, is incorporated into the DNA of dividing cells and causes photoradiosensitization. Twenty-five patients with malignant astrocytomas were treated with continuous intracarotid BUDR radiosensitization and radiotherapy for 8 1/2 weeks. Unique dose-limiting mucocutaneous complications were encountered. Ipsilateral facial dermatitis with epilation of eyebrows and eyelashes, ocular irritation, and bilateral nail dystrophy developed in all patients. Less common reactions included oral ulceration in six patients, body exanthem on the trunk in five, and atypical erythema multiforme major in one. PMID- 2584464 TI - Minocycline staining of the oral cavity. PMID- 2584463 TI - Melkersson-Rosenthal syndrome: a review of 36 patients. AB - The Melkersson-Rosenthal syndrome is an uncommon condition of uncertain pathogenesis and cause. The classic triad of signs includes recurrent orofacial edema, recurrent facial nerve palsy, and lingua plicata. We retrospectively reviewed the medical records of 36 patients (24 women and 12 men) with elements of the Melkersson-Rosenthal syndrome. The complete triad was present in 9 (25%) patients. Orofacial involvement was the dominant feature; it occurred in all 36 patients and was the presenting sign in 15 (42%). Lingua plicata occurred in 18 (50%) patients, and peripheral facial paralysis was present in 17 (47%). Fourteen biopsy specimens were obtained, all from the orofacial region. Eight specimens revealed the classic pathologic picture of granulomatous cheilitis. No etiologic agent was identified in any of the patients. Diagnosis is difficult when all features of the triad are not present. A conservative treatment approach is recommended. PMID- 2584465 TI - IgA benign monoclonal gammopathy with recurrent self-healing skin tumors. PMID- 2584466 TI - Two distinct squamous cell carcinomas in a psoriasis patient receiving low-dose cyclosporine maintenance treatment. PMID- 2584468 TI - Ulcerative syphilis in acquired immunodeficiency syndrome: a case of precocious tertiary syphilis in a patient infected with human immunodeficiency virus. PMID- 2584467 TI - Skin color reflectance measurements for objective quantification of erythema in human beings. PMID- 2584469 TI - Successful treatment of botryomycosis in a patient with acquired immunodeficiency syndrome. PMID- 2584470 TI - Hair discoloration caused by minoxidil lotion. PMID- 2584471 TI - Melanophages in inflammatory skin disease. PMID- 2584472 TI - Disseminated superficial actinic porokeratosis in pemphigus foliaceus. PMID- 2584473 TI - Incidence of malignancy in patients with generalized pruritus. PMID- 2584474 TI - Pigmented purpura-like eruption progressing to mycosis fungoides. PMID- 2584476 TI - Severe reaction to diphenhydramine. PMID- 2584475 TI - Audiologic disturbances in vitiligo. PMID- 2584477 TI - Evaluation of craniosynostosis with three-dimensional CT imaging. AB - Technological advances in computer image analysis have made possible three dimensional (3D) surface reformations of anatomic structures from contiguous axial CT slices. We have recently utilized this new imaging technique in six patients with primary, isolated craniosynostosis. In each case 3D CT demonstrated the exact extent of synostosis, and in five cases 3D CT images facilitated surgical planning by precisely localizing the proper site for craniectomy. Three dimensional CT may be a useful adjunct to imaging and surgical planning in this condition. PMID- 2584478 TI - CT features of cellulosae and racemosus neurocysticercosis. AB - Of 210 cases of cerebral neurocysticercosis studied with CT since 1982, three cases proved to be due to the rare Cysticercus racemosus (surgical verification) rather than to the much more prevalent infestation by Cysticercus cellulosae. We attempted to establish CT criteria for differentiating the more severe and always fatal form of C. racemosus. The CT appearance occasionally encountered in C. racemosus resembles a "bunch of grapes"; this appears to be the only criterion of differential value. PMID- 2584479 TI - Orbital "blow-in" fractures: clinical and CT features. AB - During a 16 month period, seven patients were admitted to our trauma center with "blow-in" fractures of the orbital roof. This injury results from a significant direct blunt force applied to the supraorbital region of the frontal bone with transmission of energy to the thin orbital plate of this bone and displacement of bone fragments downward into the superior orbit. High resolution CT with multiplanar reformation and three-dimensional display proved very useful in identifying and characterizing the bone and soft tissue abnormalities found in our patients. Our experience suggests that CT demonstration of supraorbital frontal bone fractures and/or frontal lobe cerebral contusions is an indication for thin section CT of the entire orbit, even when there is no evidence of a superior orbital rim fracture. Demonstration of an orbital blow-in fracture should prompt careful clinical assessment of the globe, optic nerve, and extraocular muscles to identify and appropriately manage underlying injuries to these structures. PMID- 2584480 TI - Impact of marrow fat on accuracy of quantitative CT. AB - An assessment of the role of marrow fat as a source of error in single energy quantitative CT (SEQCT) measurements of the spine is presented. Fat-induced shifts and spreads in SEQCT findings are discriminated and quantified. Studies using chemical analysis have reported an average vertebral bone mineral (MIN) loss of approximately 1.3 mg/ml (0.9%) per year from a peak MIN of 150 mg/ml at age 30 years with a standard error of the estimate (SEE) of approximately 23 mg/ml [coefficient of variation (CV) = 20%]; intraosseous vertebral fat content increases by approximately 2.4 mg/ml (1.4%) per year from a fat density of 175 mg/ml at age 30 years with an SEE of approximately 87.5 mg/ml (CV = 36%). If one does not adjust for the average age-related fat change, SEQCT underestimates MIN and overestimates MIN loss by 10-30% (at a scanner setting of approximately 80 kVp). Application of correction procedures reduces the average underestimation to 1-3%. The impact of residual vertebral fat variability on the accuracy of MIN measurements accounts for only 12-24% of the total accuracy error of typically 10 15 mg/ml. The impact of fat changes between zero and twice the normal age-related rate on MIN loss measurements on individual patients and patient groups (treatment versus control) accounts for only 1-2% of the total precision error of typically 1.5-3 mg/ml. From 94 to 99% of the spread of SEQCT versus age data is caused by sources of variability other than fat. All fat-related errors are higher than the above estimates by a factor of approximately 1.5-2.5 when scanning at higher voltages of up to 130 kVp. Given the limited impact of fat variability, we conclude that for most clinical applications, MIN and bone loss measurements should use SEQCT. Adjustment for the average under/overestimation (by either explicitly correcting SEQCT findings or by comparing them with normative data obtained on a similar scanner), measuring at low voltages of approximately 80 kVp, and strict compliance to quality assurance procedures are highly recommended to achieve optimum accuracy. PMID- 2584481 TI - Inversion recovery snapshot FLASH MR imaging. AB - Snapshot fast low angle shot (FLASH) magnetic resonance (MR) imaging techniques have been developed to enable real time imaging of MR parameters. The method is based on a 64 x 128 FLASH tomogram acquired within less than 200 ms. This work describes snapshot FLASH MR using a single 180 degrees pulse prior to the acquisition of a series of FLASH images. The experiment creates continuous dynamic inversion recovery (IR) T1 contrast in successive images. The total acquisition time of 16 images displaying the IR behavior is less than 4 s. Representative snapshot FLASH IR MR images of the abdomen of healthy rats and of an implanted hepatic tumor are illustrated. PMID- 2584482 TI - Improvement in signal-to-noise ratio and reduction of chemical shift and motion induced artifacts by summation of gradient and spin echo data acquisition. AB - Narrow bandwidth magnetic resonance (MR) imaging allows an increase of signal-to noise ratio (SNR) but causes increased chemical shift and motion-induced artifacts. To obtain MR images with SNR approximately equal to that obtained with narrow bandwidth but with less chemical shift and motion-induced artifact, we introduced triple readout gradient reversal centered around the spin echo. As a result, signals from two gradient echoes and a single spin echo can be collected and summed. Phantom, knee, shoulder, and abdominal MR images were obtained using a 1.5 T GE Signa System at sampling rates ranging from 10 to 60 kHz. Since the bandwidth per pixel was tripled, chemical shift misregistration was reduced by the same factor. The summation image of two gradient echoes and one spin echo had an SNR comparable with that of a single spin echo acquired within the same total sampling interval. Data acquisition at a high sampling ratio also minimizes the dispersion of T2* weighting among three echoes. In addition, summation of the three resulting images decreases motion artifact by effective averaging. PMID- 2584483 TI - Supratentorial and spinal cord hemangioblastomas: gadolinium enhanced MR appearance with pathologic correlation. AB - A case is presented that illustrates the magnetic resonance appearance of supratentorial hemangioblastomas both prior to and following intravenous administration of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). Spinal cord hemangioblastomas were also present and were visualized only after Gd DTPA administration. Pathological verification of the multiple tumoral lesions was obtained. PMID- 2584484 TI - Heterotopic brain in the middle ear: CT findings. AB - A soft tissue mass was found by CT in the mesotympanum of the left middle ear of a 4-year-old boy. This lesion was without radiologic or surgical evidence of associated bony defect or communication with the intracranial cavity. Pathological examination revealed heterotopic brain tissue. Although heterotopic brain tissue in the middle ear is rare, it should be considered in the differential diagnosis of soft tissue middle ear masses. PMID- 2584485 TI - Intracerebral extension of nasal dermoid cyst: CT appearance. AB - We report on a 46-year-old man with a congenital nasal dermoid cyst that extended intracranially to form large bifrontal intraaxial dermoid cysts, which became secondarily infected through a nasal dermal sinus tract. Computed tomography demonstrated bilateral frontal lobe ring enhancing cystic masses containing fat fluid levels consistent with dermoid cyst abscesses. Axial and coronal CT of the skull base and nose demonstrated a midline bony canal extending from two dimples on the dorsum of the patient's nose to the base of the anterior cranial fossa. The clinical, CT, and surgical findings are reviewed as well as the embryogenesis of congenital nasal dermoid cysts. PMID- 2584486 TI - CT-guided extrapleural drainage of bronchogenic cyst. AB - A patient with a subcarinal bronchogenic cyst is described. The cyst was aspirated using an extrapleural percutaneous approach under CT guidance, employing repeated injections of 4-5 ml of saline to split the parietal pleura from the chest wall. Thus we describe a technique that allows the insertion of a catheter into a cyst and complete evacuation of its contents. PMID- 2584488 TI - Hemiazygos vein aneurysm: CT documentation. AB - A case of an idiopathic aneurysm of the hemiazygos vein diagnosed by CT is presented. Then a patient with hemiazygos vein dilatation due to a known etiology is shown for comparison. PMID- 2584487 TI - Computed tomography of bronchial artery aneurysm with erosion into the esophagus. AB - Bronchial artery aneurysms are rare lesions. A case report is presented in which CT demonstrated a 7 cm enhancing mass that proved to be a mediastinal bronchial artery aneurysm. The aneurysm subsequently eroded into the esophagus, resulting in fatal exsanguination. PMID- 2584489 TI - CT appearance of diffuse peritoneal endometriosis. AB - The CT appearance of diffuse peritoneal endometriosis is presented. This entity may mimic peritoneal carcinomatosis and should be considered in females of childbearing age. PMID- 2584490 TI - Giant renal cell carcinoma: CT and MR characteristics. AB - A case of an unusually large cystic renal cell carcinoma demonstrated on plain film, CT, and magnetic resonance (MR) is presented. Though the origin of huge abdominal tumors can be difficult to determine, the CT and MR findings were able to correctly diagnose the mass as a malignant cystic kidney tumor. PMID- 2584491 TI - Lymphoma in a pelvic spleen: CT features. AB - A case of recurrent lymphoma presenting as a pelvic mass on CT is described. At surgery this proved to represent an ectopic spleen with lymphomatous infiltration. PMID- 2584492 TI - MR imaging of retroperitoneal teratoma: correlation with CT and pathology. AB - A retroperitoneal teratoma was studied with CT and magnetic resonance (MR) imaging. The images were correlated with the pathologic findings. The tumor was composed of five portions: adipose tissue, bone, hair, sebum, and loose edematous fibrofatty tissue with skin. Computed tomography and MR both demonstrated a well defined mass with separate cystic and solid components and all five tissue elements of the tumor. Magnetic resonance was superior to CT in delineating the relationship of blood vessels to the tumor. PMID- 2584493 TI - MR imaging of cavernous hemangioma of the optic chiasm. PMID- 2584494 TI - Solitary prostatic metastasis to the cerebellopontine angle: MR and CT findings. PMID- 2584495 TI - CT signs of ascending transtentorial cerebellar herniation. PMID- 2584496 TI - Intracranial protrusion of the glenoid fossa: CT findings. PMID- 2584497 TI - CT findings in primary amyloidosis of the colon. PMID- 2584498 TI - Pedunculated leiomyosarcoma of the vaginal cuff after total hysterectomy: CT features. PMID- 2584499 TI - Imaging of breast cancer with [18F]fluorodeoxyglucose and positron emission tomography. PMID- 2584500 TI - Hemangioendothelioma of bone: CT findings. PMID- 2584501 TI - Forty degree angled coronal CT scanning of scaphoid fractures through plaster and fiberglass casts. AB - A method for obtaining coronal CT scans angled 40 degrees to the longitudinal axis of the wrist, parallel to the long axis of the scaphoid, is described. Its potential for evaluating scaphoid fractures is assessed in 10 patients with healing or clinically suspected fractures. Overlapping 3 mm thick angled coronal CT scans were obtained for each patient both in and out of cast. The CT images were compared to plain films and tomography. Comparisons were also made of CT images obtained through fiberglass and plaster casts. All fractures apparent by plain films and tomography were apparent by CT; one case suspected of fracture on initial plain films showed no evidence of fracture on CT and subsequent clinical course and plain films. Osseous union of healing fractures was more reliably assessed on CT than on plain films and plain film tomography. There was no degradation of CT images by either fiberglass or plaster casts; fiberglass casts allowed easy planning of tomographic slices from scout films. We conclude that direct 40 degree angled coronal CT examination of the scaphoid is a quick reliable method to detect scaphoid fractures and to assess their healing without the need of cast removal. PMID- 2584502 TI - Coaxial needle system of MR- and CT-guided aspiration cytology. AB - The use of aspiration cytology guided by imaging devices such as ultrasound, CT, or magnetic resonance (MR) has revolutionized the evaluation of disease processes throughout the body. Previously described coaxial needle systems for interventional procedures have a variety of limitations that are particularly problematic for use in the head and neck, CNS, and other areas where critical and complex anatomy is present in a very small region. We describe a new coaxial needle system for CT- and MR-guided aspiration cytology that overcomes these limitations. PMID- 2584503 TI - Pulmonary infarction: CT appearance with pathologic correlation. AB - The CT appearance of 12 proven pulmonary infarcts in 10 patients was analyzed and correlated with pathologic appearance. The diagnosis of pulmonary infarction was clinically suspected in only 2 of the 10 patients. A pleural based parenchymal density with convex, bulging borders and linear strands directed from the apex of the density toward the hilum was noted in each case (n = 12). Other features were a truncated apex (n = 10), a broad pleural base (n = 10), and scattered areas of reduced attenuation within the lesions (n = 7). This distinctive complex of findings on CT should raise a strong suspicion of pulmonary infarction. PMID- 2584504 TI - Gadolinium-DTPA enhancement of lung radiation fibrosis. AB - Gadolinium-diethylenetriamine pentaacetic acid (DTPA) enhancement of radiation induced apical pulmonary fibrosis was observed in two patients previously treated for breast cancer. In one case the fibrosis was biopsied twice, with no change in its CT appearance over 3 years. Gadolinium-DTPA may enhance benign apical fibrosis after radiation therapy and should not, in and of itself, be used as evidence of recurrent malignancy. PMID- 2584505 TI - Infiltrated retrocrural space following thoracic aorta trauma: CT evaluation. AB - Four cases of abnormal increased soft tissue density in the retrocrural space associated with traumatic thoracic aorta laceration are presented. Although the specificity of this finding needs further study, the dense retrocrural space sign can aid in the determination of the need for thoracic aortography and subsequent identification of aortic tears. PMID- 2584506 TI - Periportal tracking in hepatic trauma: CT features. AB - In retrospective review, 51 cases of hepatic trauma were analyzed for type and location of injury. More than half of these cases (62%) demonstrated periportal zones of decreased attenuation, which is presumed to represent blood in the periportal region. This finding has been termed "periportal tracking" and may be an important sign of subtle liver injury. PMID- 2584507 TI - Hepatic perfusion during hepatic artery infusion chemotherapy: evaluation with perfusion CT and perfusion scintigraphy. AB - The standard method for the evaluation of hepatic perfusion during hepatic artery infusion (HAI) chemotherapy is planar hepatic artery perfusion scintigraphy (HAPS). Planar HAPS was performed with 2 mCi of [99mTc] macroaggregated albumin infused at 1 ml/min and compared with single photon emission CT (SPECT) HAPS and with a new study, CT performed during the slow injection of contrast material through the HAI catheter (HAI-CT). Thirteen patients underwent 16 HAI-CT studies, 14 planar HAPS studies, and 9 SPECT HAPS studies. In 13 of 14 studies (93%) HAI CT and planar HAPS were in complete agreement as to the perfusion pattern of intrahepatic metastases and normal liver. In nine studies where all modalities were performed, the findings identified by HAI-CT and planar HAPS agreed in all cases, whereas the results of two SPECT scans disagreed with the other studies. With respect to perfusion of individual metastases, 14 of 14 HAI-CT studies, 12 of 13 planar HAPS studies, and 9 of 9 SPECT HAPS studies correctly demonstrated the perfusion status of individual lesions as indicated by the pattern of changes in tumor size determined on CT obtained before and after the perfusion studies. Hepatic artery infusion CT was superior for delineation of individual metastases, particularly small lesions, and for the evaluation of nonperfused portions of the liver. Planar HAPS detected extrahepatic perfusion in four patients, and this was not detected by HAI-CT. We conclude that HAI-CT and scintigraphy are complementary techniques. Hepatic artery infusion CT has advantages for the evaluation of intrahepatic perfusion, and planar HAPS is superior to HAI-CT for the detection of extrahepatic perfusion. PMID- 2584508 TI - Comparison of conventional and computed arthrotomography with MR imaging in the evaluation of the shoulder. AB - To compare conventional arthrography and computed arthrotomography (CAT) with magnetic resonance (MR) imaging in the evaluation of the shoulder, we studied 18 patients who underwent conventional double contrast arthrography and CAT, and T1 , balanced, and T2-weighted MR imaging. The arthrograms were independently reviewed by two of the authors and the MR images were independently reviewed by three other authors in a systematic fashion with the aid of a prewritten evaluation form. The findings were compared among reviewers and between imaging methods. We found MR comparable to conventional arthrography in the evaluation of the rotator cuff; however, MR also enabled evaluation of tendonitis, which could not be accomplished with conventional arthrography. Because of MR's superior soft tissue imaging capability, we were able to stage the impingement syndrome. Magnetic resonance also allowed evaluation of the glenoid labrum and capsuloligamentous structures and assessment of instability in a fashion similar to CAT. In most cases, information obtained from MR equaled or exceeded that obtained from conventional arthrography and CAT. With refinement in technique and increased experience, we believe that MR may replace arthrography in the evaluation of the shoulder. PMID- 2584509 TI - Juxtaacetabular ganglionic (or synovial) cysts: CT and MR features. AB - Radiographic findings include supraacetabular bone erosions, subchondral acetabular cysts, soft tissue masses with or without radiolucent inclusions representing nitrogen gas, joint space narrowing, and abnormal hip configuration. Associated tears of the acetabular labrum were confirmed by arthrography in two patients. Computed tomography and magnetic resonance imaging afforded improved delineation of soft tissue ganglia and their relationship to the acetabular bone, labrum, and hip joint. We report our experience with seven patients in whom various imaging examinations clearly documented the presence of soft tissue cystic lesions adjacent to the acetabulum; in six of the seven patients, significant clinical manifestations were evident in the affected hip. Such cysts, whether designated synovial or ganglionic in type, appear to be a frequently overlooked yet important cause of hip symptomatology. PMID- 2584510 TI - MR imaging of the knee: three-dimensional volume imaging combined with fast processing. AB - A new examination protocol for patients with suspected meniscal or hyaline cartilage disorders is presented. Knees were imaged with a fast gradient echo imaging sequence with subsequent three-dimensional transformation. Data were transferred to an image processing system that allows reconstruction in any plane desired. Approximately 200 interactively positioned reconstructions are displayed and reviewed in approximately 10 min. Thirty-five patients with suspected meniscal or hyaline cartilage disorders were examined prospectively. All underwent subsequent arthroscopy. The magnetic resonance (MR) diagnosis showed an accuracy of 91.4% compared with arthroscopic findings. Owing to the short imaging time, the proposed procedure permits screening of knee joint disorders with MR. PMID- 2584511 TI - Lower cranial nerve palsy due to dissection of the internal carotid artery: CT and MR imaging. AB - Three patients with unilateral lower cranial nerve palsy underwent contrast enhanced CT and magnetic resonance (MR) imaging for the investigation of possible compressive pathology in the region of the jugular foramen. Computed tomography revealed a mural crescentic hypodensity of the corresponding internal carotid artery (ICA) in two patients and a faulty visualization of the vessel in one. Magnetic resonance revealed a corresponding hyperintense lesion expanding the wall and narrowing the lumen of the cervical ICA on both T1- and T2-weighted images. Dissection of the ICA was confirmed by angiography in all three patients. Among the possible etiologies of lower cranial nerve palsy, a dissecting hematoma of the cervical ICA must be considered, which can be diagnosed by CT and MR. PMID- 2584513 TI - Dental research: problems, progress, and prognosis. PMID- 2584512 TI - Cerebral asymmetry: MR planimetry of the human planum temporale. AB - A method is described for the imaging and planimetric measurement of the planum temporale (PT) using computer reformations from three-dimensional fast low angle shot magnetic resonance (MR) data. The procedure allows the determination of size and left-right asymmetry of this area on the posterior supratemporal surface, which has been assumed by previous investigators to be a structural correlate of speech lateralization. To establish a consistent method for future studies, special effort was invested in the elaboration of reliable imaging criteria for the borders of the PT. The authors report MR planimetric measurements of the PT in 10 human cadaver brains performed independently and in a "blinded" fashion by two observers. A high degree of interobserver agreement was found, demonstrating the reliability of the MR criteria for PT delineation. The planimetric data correlated with those from subsequent anatomic measurements following section of the same specimens. The left-right ratios of PT size were almost the same with both methods (mean 1.9). Magnetic resonance planimetry of the PT is a noninvasive, reliable, and quantitative procedure to determine gross cerebral asymmetry in the posterior speech area. PMID- 2584514 TI - Whither peer review? PMID- 2584515 TI - Effect of exercise on salivary composition and cortisol in serum and saliva in man. AB - The effect of exercise on electrolytes and cortisol levels in serum and saliva was examined in 27 young, healthy male volunteers who performed graded submaximal cycle exercise for nine min at up to 85% of their age-predicted maximal heart rate. Seventeen men performed the Wingate anaerobic test for 30 s. A significant increase in pulse rate and systolic blood pressure and a decrease in diastolic blood pressure were found, and serum concentrations of Na+, K+, and lactate were significantly elevated immediately after exercise. A nonsignificant increase in saliva and serum cortisol levels was found. Significantly lowered salivary flow rate and elevated salivary K+, protein, and lactate concentrations were found within ten min after exercise. Salivary Mg2+ was significantly elevated after anaerobic exercise only. PMID- 2584516 TI - Scanning electron microscopic characterization of sensitive vs. insensitive human radicular dentin. AB - Our aim was to investigate the structural changes of dentinal tubules in specimens obtained from both hypersensitive and naturally desensitized areas in wedge-shaped defects on the same exposed cervical dentin surface of a hypersensitive tooth. A new biopsy technique that makes use of a hollow, cylindrical diamond bur was designed so that specimens from exposed root dentin of vital teeth could be obtained. Twenty-two dentin biopsy pairs were divided into two groups; one was prepared for scanning electron microscopy (SEM) and the other for microradiography (MR). Small hypersensitive areas were identified by a scratch test on exposed human dentin in vivo. SEM observation of the dentin biopsies showed that the orifices of many dentinal tubules in hypersensitive areas were open and that membranous structures appeared on the walls of dentinal tubules. In naturally desensitized areas on the same dentin surface, most of the dentinal tubules were obturated with rhombohedral crystals of all sizes; membranous structures were not observed in these tubules. These results showed that hypersensitivity occurred on the exposed dentin when most of the tubular orifices were open. PMID- 2584517 TI - A cytochemical study of horseradish peroxidase uptake in rat junctional epithelium. AB - The uptake of horseradish peroxidase (HRP) was studied in rat junctional epithelium (JE). Intravenous HRP (12.5 mg, 25 mg, or 50 mg) was only endocytosed by the entire JE (particularly by the coronal portion of the JE). Although HRP uptake was negligible at a concentration of 12.5 mg, marked uptake was observed at concentrations of 25 mg and 50 mg. However, there was no difference in the HRP uptake by the JE between the concentrations of 25 mg and 50 mg. By electron microscopy, HRP was detected in the organellae (micropinocytotic vesicles, intracytoplasmic vacuoles, dense bodies, and multivesicular bodies) in the junctional epithelial cells (JE cells). HRP-positive micropinocytotic vesicles were detected in all JE cells. However, intracytoplasmic vacuoles, which are characteristically observed in JE cells, were not always positive for HRP. Numerous HRP-negative vacuoles were detected in the JE cells. The number of HRP positive organellae in the coronal portion of the JE was pronounced, compared with those in other portions. These findings provided evidence that the entire JE, especially its coronal portion, has endocytotic ability by micropinocytotic vesicles, rather than intracytoplasmic vacuoles, for foreign substances. PMID- 2584518 TI - Differences in the rate of molar wear between monkeys raised on different diets. AB - The purpose of this study was to make detailed comparisons of rates and patterns of tooth wear in 15 growing vervet monkeys raised on hard vs. soft diets. Dental impressions were taken every six to eight weeks over a four-year period. Cusp heights and areas of dentin exposure on the buccal cusps of the left mandibular first molar were measured from high-resolution epoxy casts, by use of a Reflex Measuring Microscope. Areas of dentin exposure were regressed against time (by use of least-squares regression) so that the course of tooth wear in animals from both diet groups could be charted. By use of a two-sample t test and the Mann Whitney test, slopes of the regressions and changes in cusp height were compared between diet groups. In both comparisons, animals raised on the hard diet showed more rapid tooth wear than did animals raised on the soft diet. Analyses of other parameters indicate that this was probably because of differences in dietary consistency between the two groups. PMID- 2584519 TI - Microscopic and crystallographic examinations of the teeth of the X-linked hypophosphatemic mouse. AB - Teeth from the C57BL/6J-Hyp mouse (Hyp mouse) were examined histologically, radiographically, and crystallographically. Microscopic examinations of the ground sections, the decalcified and H-E-stained sections, and the contact microradiograms of molars and incisors from the Hyp mouse showed several abnormalities--such as large pulp chamber, wide predentin, thin dentin at the pulp floor, and multiple occurrences of interglobular dentin. Powder and microbeam x-ray diffraction analyses showed that the crystallinity of hydroxyapatite in incisor globular dentin from the Hyp mouse was higher than that in incisor dentin from the normal mouse. On the other hand, the findings of transmission electron microscopy demonstrated that the sizes of hydroxyapatite crystals of globular dentin in the Hyp incisor were larger than those in normal incisor dentin. These results demonstrated that the findings in Hyp mouse teeth were in accord with those of human XLH teeth. PMID- 2584520 TI - Genotoxic evaluation of chronic fluoride exposure: micronucleus and sperm morphology studies. AB - The purpose of this study was to investigate the genotoxic effects of chronic fluoride exposure on mammalian cells in vivo by use of the mouse bone-marrow micronucleus test and the sperm morphology methodology. Mice of genotype B6C3F1 were obtained at weaning and maintained on a low-fluoride diet (less than 0.2 ppm F) ad libitum throughout the experiment. The animals were randomly assigned to seven groups and given fluoride (as sodium fluoride) in concentrations ranging from 1.0 to 75 ppm in the drinking water. Negative (distilled water) and positive (cyclophosphamide) controls were included. After a 21-week treatment period, the animals were killed by cervical dislocation, and blood was obtained by cardiac puncture. Slides of femur marrow cells were prepared and blindly examined for the frequency of micronucleated polychromatic erythrocytes (MN-PCE). Slides of sperm from the cauda epididymides of the male mice were also prepared and similarly examined for morphological abnormalities. Weight of the testes was recorded, and the plasma, humeri, testes, and carcasses were saved for fluoride analyses. Analyses of bone and plasma fluoride confirmed the effective absorption of fluoride following ingestion. The frequency of MN-PCE, the count of abnormal sperm, and the weight of the testes for mice chronically exposed to fluoride, in doses ranging from approximately 0.3 to 23 mg/kg/day, were not significantly different from those of the negative control animals. The results of this study support the view that fluoride has no genotoxic effects. PMID- 2584521 TI - Output from visible-light activation units and depth of cure of light-activated composites. AB - A simple and reproducible method for monitoring the intensity of radiation from composite light-activation units has been developed. The method depends upon the use of a cadmium sulfide photo-conductive cell, the electrical resistance of which varies with the amount of light falling upon its surface. Filters were used for selection of the wavelength of light that is thought to be most effective in activating polymerization. The use of broad-band wavelength filters failed to give results for light intensity that correlated with depth of cure. Narrow-band interference filters, having a band width of only 10 nm and being selective within the wavelength range of from 460 to 480 nm, produced results for light intensity that correlated with depth of cure. The depths of cure for various types of composite material were measured with use of a penetrometer that enabled the thickness of unpolymerized material at the base of the test mould to be determined. The depth of cure was inversely proportional to the attenuation of light caused by the composite resin at 470 nm. The relationship between depth of cure and light intensity at 470 nm was not a simple linear one over all intensity values. Above a certain critical value of intensity (about 550 lux for a 3.5-mm aperture in these experiments), the depth of cure appeared to be almost independent of intensity. Below this critical value, depth of cure fell markedly with decreasing intensity. PMID- 2584522 TI - Stiffness of endodontically-treated teeth related to restoration technique. AB - Endodontically-treated posterior teeth are susceptible to fracture; consequently, full-occlusal-coverage restorations are recommended. We designed this study to examine the potential for alternative restorative techniques for pulpless teeth, using strain gauges mounted on extracted maxillary second premolars to measure strains generated by nondestructive occlusal loading. Cuspal stiffness was evaluated on the following sequentially performed procedures: unaltered tooth, completion of all endodontic procedures, appropriate restorative preparation, and restoration. The restorative procedures evaluated were: (1) amalgam, (2) cast gold onlay, (3) composite restoration with enamel etch, and (4) composite restoration with enamel and dentin etch. Finally, all teeth were loaded to fracture. Cast gold was the strongest restorative material tested (2.11 relative stiffness, compared with that of the unaltered tooth at 1.00), and amalgam was the weakest (0.35 relative stiffness). Composite restoration and enamel plus dentin etch were almost as strong as the unaltered tooth (0.87 relative stiffness), while enamel-etch-only yielded lower stiffness (0.51). PMID- 2584524 TI - IAET strategic planning report: chapters IV, V, VI. PMID- 2584523 TI - Geriatric dentistry: a pressing need. PMID- 2584525 TI - Patient adjustment to an ileal conduit after radical cystectomy. PMID- 2584526 TI - Standards of care. Patient with colostomy. Part II. International Association of Enterostomal Therapy. PMID- 2584527 TI - Cultivating time management skills. PMID- 2584528 TI - Administering suppository via stoma. PMID- 2584529 TI - Gosnell pressure sore risk assessment instrument revision. PMID- 2584530 TI - [Mechanisms of the antitumor action of spirobromine in mice with leukemia P-388]. AB - The influence of new antitumor drug, spirobromine, a derivative of dispirotripiperazine, on DNA synthesis in tumor cells and organs at different times after its injection into mice with P388 leukemia has been studied. The duration of DNA synthesis inhibition in tumor cells was found to correlate with spirobromine antitumor activity. A certain selectivity of action of the studied compound on DNA synthesis in P 388 leukemia cells as compared to the action on DNA synthesis in bone marrow, small intestine, spleen and liver of tumor animals was observed. PMID- 2584531 TI - [The effect of a one-time administration of phenobarbital and carbon tetrachloride on comuton activity in the rat liver]. AB - Infusion of phenobarbital and CCl4 was found to induce comuton control of mitochondrial respiration in a liver of starved rats. Comuton regulation of liver mitochondria respiration can be activated either by increase in liver activity or by damage caused by CCl4. The comuton regulation is directly induced by disturbance of energetic homeostasis of liver cells. PMID- 2584532 TI - [Biomedical aspects of the stereoisomerism of biomolecules]. AB - A concept of "racemate lock" has been proposed. This "lock" switches off certain biochemical processes in an organism by increasing concentration of nonspecific stereoisomer of the corresponding metabolite. A program of research of this concept has been discussed. PMID- 2584533 TI - [Changes in the membrane structure of the brain microsomes in cats with electrodes implanted in the inner ear]. AB - Using spin-labels it was shown that electrode implantation into the cats scala media resulted in structure reconstruction of microsome membranes of auditory zones in cats brain. Membrane fluidity increased but there was no change of surface potential. The changes of microviscosity were found during the first month after the implantation. Five months later the order parameter returned to the mean valve for cats in control group without electrodes. PMID- 2584534 TI - [UV-induced formation of DNA-protein cross-links in chromatin in the presence of chemical agents]. AB - Hindered phenols, quinones, and SH-compounds have been studied as possible protectors and sensitizers of DNA-protein cross-linking in chromatin. Efficacy of cross-linking was estimated by the quantity of protein linked to DNA after UV irradiation at 254 um in the presence of chemical agents. Phenols and quinones exert protective influence on cross-linking whereas DNA-protein cross-links are sensibilized by cysteine hydrochloride. PMID- 2584536 TI - The Care Card--a new medical records application in British health care. PMID- 2584535 TI - [Changes in the level of sulfhydryl groups in the organs and blood of mice administered a highly dispersed iron powder against a background of developing anemia]. AB - Alimentary iron deficiency causes significant changes in thiol content: the increase in the content of protein sulfhydryl groups in organs at late stages and the decrease in that of non-protein sulfhydryl groups at early stages of experiment. A preliminary introduction of 10 mg/kg fine iron powder (FIP) into animals fed iron-free food leads to the decrease in sulfhydryl group content in organs and blood of experimental mice. The decrease in sulfhydryl group content at FIP introduction might be connected with changes in activity of glutathione dependent enzymes. PMID- 2584537 TI - Testing for HIV infection without consent: new guidelines from the Royal College of Psychiatrists. PMID- 2584538 TI - The nurse's role in giving pre-operative information to reduce anxiety in patients admitted to hospital for elective minor surgery. AB - Hospitalization, regardless of disease, is known to provoke anxiety in the patient admitted for minor surgery. If unrecognized, prolonged anxiety creates stress which may subsequently harm the patient and delay recovery. If nursing intervention is to be therapeutic, it is argued that recognition of and response to this area of patient need should be based on current research findings within the framework of a nursing model. The relationships between pre-operative anxiety, types of coping strategy and information received are discussed with reference to current literature. Open-ended and flexible assessment formats based on Orem's therapeutic self-care requirements and King's open-systems framework are proposed. PMID- 2584539 TI - Geriatric versus general medical wards: comparison of patients' behaviours following discharge from an acute care hospital. AB - The objective of this study was to explore, from a nursing perspective, the effectiveness of geriatric wards in preparing elderly patients for discharge from an acute care hospital. A convenience sample of 40 patients aged 70 years or older was obtained from three geriatric medical wards and two general medical wards of a large British teaching hospital. Data were collected immediately prior to discharge, and after 6 and 13 weeks following discharge. No meaningful differences were found between the two patient-groups in their ability to cope with activities of daily living following discharge. The majority of deaths and/or hospital readmissions occurred within 6 weeks of discharge. A major concern identified in both groups was patients' lack of knowledge about medications and their side-effects. A need for more effective teaching programmes for elderly patients was identified. PMID- 2584540 TI - Staff nurses' attitudes toward nursing research: a descriptive survey. AB - Staff nurse involvement in clinical nursing research is dependent on the attitudes nurses hold toward research. An exploration of these attitudes was undertaken in a 464-bed midwestern teaching hospital as it developed its nursing research procedures. A questionnaire was developed which incorporated the Boothe Attitudes on Nursing Research Scale. All registered nurses (n = 925) at the facility were surveyed with a response rate of 77.8% (n = 720). Findings indicated that many nurses were interested in research and believed that the institution would support research activities and the implementation of research findings. Some deterrences to conducting research included: time, lack of knowledge, and the nurses's perception of the supervisory support and the research support services. PMID- 2584541 TI - Knowledge and perception of AIDS among Canadian nurses. AB - Within the growing literature on AIDS, relatively little attention has been paid to the public's knowledge and perception of the disease. Even less is known about nurse's understanding of, and attitudes towards AIDS, even though in large part, the treatment and care of AIDS patients rests in their hands. As a partial corrective to this deficiency, this study offers a comparative examination of AIDS-related beliefs and attitudes held by nursing practitioners and nursing students in Canada. Briefly stated, what the research reveals is that Canadian nurses are less than fully informed about the disease and have over-cautious attitudes towards the care of AIDS patients. Among nursing students, lack of information is also a serious problem, although this group does tend to view AIDS patient care in a somewhat more liberal manner. It is apparent from these results that more attention needs to be paid to enhancing knowledge of, and changing attitudes towards, AIDS in the education of Canadian nurses. PMID- 2584542 TI - Addressing the needs of informal carers: a neglected area of nursing practice. AB - The British government's philosophy of maintaining dependency groups in the community, coupled with the rising numbers of frail elderly and dwindling pool of informal carers, has highlighted the need for appropriate professional interventions in this area. However, a failure to adequately conceptualize the needs of carers has, in the past, resulted in interventions often being inappropriate, irrelevant or unavailable. This paper advocates a major role for the nursing profession in redressing this balance. Using the findings of a postal survey on the problems and satisfactions of caring, the authors suggest how nurses might modify their current practice to maximize their contribution to this important but neglected area of their work. PMID- 2584543 TI - Perceptions of self-care in Sweden: a cross-cultural replication. AB - This cross-cultural study attempted to replicate the nursing phenomena of self care and self-concept using two self-reporting instruments. Both instruments were translated from English into Swedish and administered on a convenience basis to 187 Swedish subjects, 117 women and 70 men, ages 19-66, compulsory to university educated, and residing in the southern districts of Sweden. Swedish mean self care scores were lower (112.5) than the United States normative group of university nursing and psychology students, but the mean was comparable to East German (113.6) reported from an earlier study. Self-concept scores were similar to Nebraska teachers and East Germans. Alpha coefficients were used to assess reliability, ANOVA for differences, and item correlation of self-care agency were organized by factor analysis with four subfactors identified. The derived subscales appeared to identify potentially useful factors to aid in unravelling the complexity of the self-care agency construct. Study limitations were addressed. Cross-cultural directives for international nursing are discussed. PMID- 2584544 TI - Teaching psychomotor skills in nursing: a randomized control trial. AB - Historically, McMaster University School of Nursing in Hamilton, Ontario, Canada has utilized self-directed learning methods to teach psychomotor nursing skills to undergraduate nursing students. Second year students, in their post-clinical evaluations indicated a desire for a structured laboratory setting to assist them in acquiring these skills. In response, faculty designed a randomized control trial to compare the effectiveness of teaching psychomotor skills in a structured laboratory setting with self-directed self-taught modules. The results of this study substantiated the hypothesis of no difference between psychomotor skill performance of students who learn in a self-directed manner and those taught in a structured clinical laboratory. PMID- 2584545 TI - Lack of care givers' knowledge causes unnecessary suffering in elderly patients. AB - A comparative study of the personal hygiene of two groups of elderly women was carried out. The control group consisted of 35 healthy women aged 70-86. The experimental group consisted of 28 women aged 66-96 who were hospitalized in long term care wards and who received help with their personal hygiene. The results show that care givers lack knowledge about the normal physiological ageing process in women, which prevents them from applying the eighth component of Virginia Henderson's nursing theory. In the group who received help with their personal hygiene, 25 (89%) had abnormal genital problems. PMID- 2584546 TI - Medications of elderly institutionalized incontinent females. AB - The purpose of the study was to explore drug use of elderly incontinent female nursing home residents, to identify potential drug--drug interactions, and to identify the number and categories of drugs taken having the potential to cause urinary incontinence. The medication administration records of 84 female residents were examined. The drugs were categorized by therapeutic classification as designated by the American Hospital Formulary Service. Potential drug--drug interactions were identified using The Hansten Drug Interaction Knowledge Base Program, a microcomputer version of Hansten's (1985) book Drug Interactions. Data were computer-coded and analysed using the Statistical Analysis System (SAS). A total of 454 drugs was taken by the 84 subjects, with an overall average of 5.40 drugs per person. The most frequently taken drugs were gastrointestinal drugs, central nervous system agents, electrolytic, caloric, and water balance drugs, and cardiovascular drugs. Fifty per cent (n = 42) of the subjects were identified as having 119 potential drug-drug interactions. Seventy per cent (n = 59) of the subjects were taking a drug having the potential to cause urinary incontinence. Suggestions for future research are presented. PMID- 2584548 TI - Long-term ischemic risks after successful thrombolysis for acute myocardial infarction. PMID- 2584547 TI - Long-term benefit of early thrombolytic therapy in patients with acute myocardial infarction: 5 year follow-up of a trial conducted by the Interuniversity Cardiology Institute of The Netherlands. AB - Patients (n = 533) who participated in the Interuniversity Cardiology Institute of the Netherlands Trial were followed up for 3 to 7 years. The 5 year survival rate after thrombolytic therapy with intracoronary streptokinase was 81% (269 patients) compared with 71% after conventional therapy (264 patients). The greatest improvement in survival was observed in patients with anterior infarction (81% versus 64% with thrombolytic therapy or conventional therapy, respectively), in those with heart failure on admission or a previous infarction and in those with extensive myocardial ischemia on admission. Left ventricular ejection fraction at the time of hospital discharge was better after thrombolytic therapy. In the hospital survivors, long-term outcome was related to left ventricular function at the time of discharge and, to a lesser extent, to the underlying coronary artery disease. The initial therapy (thrombolysis or conventional) was not an independent additional determinant of long-term survival when left ventricular function and coronary status at the time of hospital discharge were taken into account. Thus, the salutary effects of thrombolytic therapy appear to be the result of myocardial salvage. Reinfarction within 3 years was observed more frequently after thrombolytic therapy, particularly in patients with inferior wall infarction and those with greater than or equal to 90% stenosis of the infarct-related vessel at discharge. Coronary bypass surgery and coronary angioplasty were performed more frequently after thrombolytic therapy than in conventionally treated patients. At 5 years, approximately 40% of patients in both groups had an uneventful course without reinfarction or additional revascularization procedures. These observations demonstrate that the benefits of thrombolytic therapy are maintained throughout 5 years of follow up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584549 TI - The role of silent ischemia, the arrhythmic substrate and the short-long sequence in the genesis of sudden cardiac death. AB - To study the role of silent ischemia and the arrhythmic substrate in the genesis of sudden cardiac death, 67 patients were studied (mean age 62 +/- 12 years). Of these, 14 patients (Group 1) had an in-hospital episode of ventricular tachycardia or fibrillation while wearing a 24 h Holter ambulatory electrocardiographic (ECG) monitor, 33 (Group II) had a documented episode of sustained ventricular tachycardia or fibrillation, or both, and 20 (Group III) had angina pectoris but no ventricular tachycardia or fibrillation. Eight Group I survivors underwent programmed electrical stimulation or ECG signal averaging, or both. All Group II patients underwent 24 h Holter monitoring and ECG signal averaging to detect late potentials before programmed electrical stimulation. Group III patients underwent both 24 h Holter recording and coronary angiography. The 24 h ECG tapes were analyzed for ST segment changes, prematurity index and characteristics of ventricular premature depolarizations. Any ST depression greater than or equal to 1 mm for greater than 30 s was considered to be a reflection of silent ischemia, and the induction of ventricular tachycardia or fibrillation by programmed electrical stimulation or the presence of late potentials, or both, was considered to be a reflection of the arrhythmia substrate. Silent ischemia preceded ventricular tachycardia in only 2 (14%) of the 14 Group I patients. The prematurity index was less than 1 in only 18% of ventricular tachycardia episodes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584550 TI - Neurally mediated hypotension and bradycardia: which nerves? How mediated? PMID- 2584551 TI - Prognostic importance of silent myocardial ischemia detected by intravenous dipyridamole thallium myocardial imaging in asymptomatic patients with coronary artery disease. AB - One hundred seven asymptomatic patients who underwent intravenous dipyridamole thallium imaging were evaluated to determine prognostic indicators of subsequent cardiac events over an average follow-up period of 14 +/- 10 months. Univariate analysis of 18 clinical, scintigraphic and angiographic variables revealed that a reversible thallium defect, a combined fixed and reversible thallium defect, number of segmental thallium defects and extent of coronary artery disease were significant predictors of subsequent cardiac events. Of the 13 patients who died or had a nonfatal infarction, 12 had a reversible thallium defect. Stepwise logistic regression analysis selected a reversible thallium defect as the only significant predictor of cardiac events. When death or myocardial infarction was the outcome variable, a combined fixed and reversible thallium defect was the only predictor of outcome. In patients without previous myocardial infarction, the cardiac event rate was significantly greater in those with an abnormal versus normal thallium scan (55% versus 12%, p less than 0.001). Thus, intravenous dipyridamole thallium scintigraphy is a useful noninvasive test to risk stratify asymptomatic patients with coronary artery disease. A reversible thallium defect most likely indicates silent myocardial ischemia in a sizable fraction of patients in this clinical subset and is associated with an unfavorable prognosis. PMID- 2584552 TI - Dipyridamole thallium-201 scintigraphy: an excellent alternative to exercise scintigraphy. PMID- 2584553 TI - Value of two-dimensional echocardiography in selecting patients and balloon sizes for percutaneous balloon mitral valvuloplasty. AB - The effect of valvular and subvalvular morphologic features and balloon size/mitral anulus size ratio on results of valvuloplasty were prospectively studied in 38 consecutive patients undergoing mitral valvuloplasty. The severity of valvular and subvalvular disease was graded echocardiographically from grade I to IV (mild to severe) for immobility, thickening, calcification of mitral leaflets and subvalvular thickening and fusion, yielding a maximal total score of 16. The diastolic mitral anulus diameter was measured in the apical four chamber view. After valvuloplasty, the mitral valve area increased from 0.9 +/- 0.3 to 2.2 +/- 0.5 cm2 (p less than 0.001) with increasing mitral regurgitation in 12 (32%) of the 38 patients. Multiple stepwise analysis revealed that the ratio of balloon size and annular size and the severity of subvalvular disease are two independent factors that correlated significantly with the mitral valve area after valvuloplasty (multiple r = 0.65, p less than 0.0002). One of 34 patients with mild subvalvular disease of grade III or less had an unsatisfactory increase in mitral valve area to less than or equal to 1.5 cm2, whereas 3 of 4 patients with severe (grade IV) subvalvular disease had a valve area less than or equal to 1.5 cm2 (p less than 0.002) after valvuloplasty. The increase in mitral regurgitation after valvuloplasty correlated significantly with the ratio of balloon to mitral anulus size and the severity of subvalvular disease (multiple r = 0.53, p less than 0.003). (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584554 TI - Cognitive function in patients with symptomatic dilated cardiomyopathy before and after cardiac transplantation. AB - Pre- and postoperative cognitive performance of candidates for heart transplantation was examined by means of an extensive battery of neuropsychological measures. A total of 54 patients completed the preoperative cognitive protocol, 20 of whom also completed postoperative testing. Age (less than 50 or greater than or equal to 50 years of age) and the primary cause of cardiac deterioration (idiopathic, ischemic disease or rheumatic/congenital defects) were the major classification variables. The main findings of this study were: 1) Preoperative neuropsychological measures revealed a high frequency of impaired performance, particularly in measures of memory, higher level processing of information and motor speed. A pattern consistent with diffuse rather than focal or lateralized cerebral deficits was observed. Significant differences were not found on the basis of the cause of cardiac disease, but some were observed for age (the older group was more impaired). 2) A comparison of pre- and postoperative cognitive scores failed to show significant cognitive improvement despite greatly improved physical health. The cause of cardiac deterioration was not differentially associated with postoperative cognitive performance, and there was equivocal evidence for age effects. These findings may have implications for the selection of transplant recipients and the timing of transplantation surgery. PMID- 2584555 TI - Technetium-99m isonitrile myocardial uptake at rest. I. Relation to severity of coronary artery stenosis. AB - To determine the potential of planar technetium-99m methoxybutyl isonitrile myocardial imaging as a method of detecting totally occluded or severely stenosed coronary arteries, the regional distribution of technetium-99m isonitrile at rest was compared with the coronary anatomy in 38 patients with prior myocardial infarction who underwent coronary arteriography. Left ventricular technetium-99m isonitrile tracer uptake at rest was assessed in the three major coronary vascular territories. When qualitative rest technetium-99m isonitrile uptake was markedly reduced or absent (grade 0), there was a 91% probability of finding a totally occluded or severely stenosed coronary artery. When qualitative tracer uptake was reduced (grade 1) or normal (grade 2), it excluded all territories supplied by a totally occluded vessel with poor collateral flow. Quantitative technetium-99m isonitrile uptake (mean +/- 1 standard deviation) in territories supplied by an occluded coronary artery with poor collateral flow (42 +/- 21%) was lower than in territories supplied by a vessel with less than 50% stenosis (87 +/- 10%) and 50 to 99% stenosis (74 +/- 19%) (p less than 0.001). Furthermore, technetium-99m isonitrile uptake in areas supplied by an occluded coronary artery with good collateral flow (61 +/- 23%) was lower than in areas supplied by a vessel with less than 50% stenosis (87 +/- 10%) (p less than 0.001). Because rest technetium-99m isonitrile imaging detects coronary occlusion with poor collateral flow, this method may be useful in assessing patients with acute myocardial infarction. PMID- 2584556 TI - Technetium-99m isonitrile myocardial uptake at rest. II. Relation to clinical markers of potential viability. AB - To determine the utility of rest-injected technetium-99m methoxybutyl isonitrile (Tc-99m isonitrile) uptake as a marker of myocardial viability, the regional uptake of this agent was compared with regional wall motion by equilibrium gated blood pool scan in 26 patients with previous myocardial infarction and with postrevascularization uptake in 8 patients after coronary bypass surgery. Rest left ventricular Tc-99m isonitrile uptake was assessed qualitatively in three coronary vascular territories as grade 0 (markedly reduced) to grade 2 (normal), and quantitatively by circumferential profile analysis. Wall motion was scored qualitatively in corresponding vascular territories as normal, hypokinetic or akinetic/dyskinetic. There was an overall relation between qualitative Tc-99m isonitrile uptake and wall motion. Abnormal wall motion occurred in 74% of vascular territories with perfusion grade 0, in 61% of those with grade 1 and in 30% of those with grade 2; however, 26% of territories with grade 0 uptake had normal wall motion. In the territories visually assigned perfusion grade 0, quantitative isonitrile uptake (mean value +/- SD) was higher when corresponding wall motion was normal or hypokinetic (62 +/- 15%) than when akinesia was detected by gated blood pool scan (39 +/- 16%, p less than 0.02). Qualitative Tc 99m isonitrile uptake improved after coronary bypass surgery in 12 of 13 territories with reduced uptake preoperatively; this included all 5 territories with a preoperative Tc-99m isonitrile score of 0. Quantitative uptake in these regions increased from 55 +/- 18% to 73 +/- 21% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584557 TI - Technetium-99m isonitrile: a perfusion or a viability agent? PMID- 2584559 TI - Single photon emission computed tomography (SPECT): 1989 and beyond. PMID- 2584558 TI - Quantitative single photon emission computed thallium-201 tomography for detection and localization of coronary artery disease: optimization and prospective validation of a new technique. AB - One hundred eight-three men underwent stress-redistribution thallium-201 myocardial perfusion tomography. After evaluation of various preprocessing filters in a phantom study, the Butterworth filter with a frequency cutoff of 0.2 cycles/pixel, order 5 (which provided optimal filter power) was used in the back projection algorithm of the patient studies. All short-axis and apical portions of vertical long-axis images were quantified by dividing each myocardial slice into 60 equal sectors and displaying the maximal count per sector as a linear profile. In a pilot group consisting of 20 normal men (less than 5% likelihood of coronary artery disease) and 25 men with coronary artery disease (greater than or equal to 50% coronary stenosis by angiography), profiles representing the lowest observed value below the mean normal profiles provided the best threshold for defining normal limits. Abnormal portions of the patient profiles were plotted on a two-dimensional polar map. The polar map was divided into 102 sectors, and sectors with a probability of greater than or equal to 80% for disease of each one of the three major coronary arteries were clustered to represent specific coronary artery territories. Receiver operating characteristic curve analysis for defect size showed that the optimal threshold for defining a definite perfusion defect was 12% for the left anterior descending and left circumflex and 8% for the right coronary artery territories. These criteria were prospectively applied to an additional 92 patients with angiographic coronary artery disease, 18 patients with normal coronary arteriograms and 28 patients with less than 5% likelihood of coronary disease. Sensitivity, specificity (in patients with normal coronary arteriograms) and normalcy rate (in patients with less than 5% likelihood of coronary artery disease) for overall detection of coronary disease were 96%, 56% and 86%, respectively. Sensitivity and specificity for identification of individual diseased vessels were, respectively, 78% and 85% for the left anterior descending, 79% and 60% for the left circumflex and 81% and 71% for the right coronary artery. These results were not significantly different from those of the pilot group. An optimized quantitative method for interpretation of stress thallium-201 myocardial perfusion tomography has been developed. Prospective application of this method indicates that the technique is accurate for the overall detection of coronary artery disease and identification of disease in individual arteries. PMID- 2584560 TI - Characteristic Doppler echocardiographic pattern of mitral inflow velocity in severe aortic regurgitation. AB - In symptomatic severe aortic regurgitation, left ventricular diastolic pressure increases rapidly, often exceeding left atrial pressure in late diastole. This characteristic hemodynamic change should be reflected in the Doppler mitral inflow velocity, which is the direct result of the diastolic pressure difference between the left ventricle and left atrium. Mitral inflow velocity was obtained by pulsed wave Doppler echocardiography in 11 patients (6 men, 5 women: mean age 53 years) with severe symptomatic aortic regurgitation and compared with normal values from 11 sex- and age-matched control subjects. The following Doppler variables were determined: velocity of early filling wave (E), velocity of late filling wave due to atrial contraction (A), E to A ratio (E/A), deceleration time and pressure half-time. In severe aortic regurgitation, E and E/A (1.13 m/s and 3.3, respectively) were significantly higher (p less than 0.001) than normal (0.60 m/s and 1.5, respectively). Deceleration time and pressure half-time (117 and 34 ms, respectively) were significantly shorter (p less than 0.001) than normal (203 and 59 ms, respectively). Late filling wave velocity (A) was not statistically different in the two groups, although it tended to be lower in the patient group (0.39 versus 0.50 m/s). Diastolic mitral regurgitation was present in eight patients (73%). M-mode echocardiography of the mitral valve, performed in 10 patients, showed that only 3 (30%) had premature mitral valve closure. In symptomatic severe aortic regurgitation, the Doppler mitral inflow velocity pattern is characteristic, with increased early filling wave velocity (E) and early to late filling wave ratio (E/A) and decreased deceleration time of the E wave.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584561 TI - Insights into the physiologic significance of the mitral inflow velocity pattern. PMID- 2584562 TI - The value of cine nuclear magnetic resonance imaging for assessing regional ventricular function. AB - Previous nuclear magnetic resonance (NMR) imaging studies to assess left ventricular function have used multiple axial planes, which are compromised by partial volume effects and are time consuming to acquire and analyze. Accordingly, an imaging approach using cine NMR and planes aligned with the true cardiac axes of the left ventricle was developed in views comparable with left ventricular cineangiography. Cine NMR imaging was used to assess regional wall motion and was validated by comparison with biplane left ventricular cineangiography. Fifty-nine patients underwent cineangiographic and NMR studies within 72 h. A poor quality NMR study precluded analysis in 4. leaving a study group of 55 patients (mean age 58 +/- 12: 17 women). Cine NMR movie loops were acquired in two long-axis planes: 1) right anterior oblique plane, parallel to the septum, and 2) four chamber orthogonal plane, perpendicular to the septum (this view is comparable to the angiographic left anterior oblique view). To assess regional wall motion, the left ventricle in both cine NMR and cineangiographic images was divided into five segments and graded on a five point grading scale from 3 for normal through 0 for akinesia and -1 for dyskinesia. Regional wall thickening was used qualitatively to aid in the analysis of wall motion. For the 275 segments compared in the right anterior oblique view, agreement was within one grade in 263 (95.6%) of 275 segments, whereas absolute agreement was observed in 171 (62%) of 275 segments. In the left anterior oblique view, of 200 segments evaluated, agreement within one grade was achieved in 184 segments (92%) and agreement was complete in 132 (66%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584563 TI - Fast Fourier transformation of the entire low amplitude late QRS potential to predict ventricular tachycardia. AB - Signal-averaged electrocardiograms (X, Y and Z leads) were acquired from 24 patients with coronary artery disease and recurrent ventricular tachycardia, 24 control patients with coronary artery disease and 23 normal subjects to assess the discriminant value of fast Fourier transformation of the entire late potential period of the QRS complex. Analysis of the vector magnitude in the temporal domain (25 to 250 Hz bandpass filters) measured high frequency QRS duration, the duration of terminal signals less than 40 microV and the root mean square voltage of the last 40 ms. Late potentials were defined as terminal signals greater than 25 Hz that were less than 40 microV. Analysis in the frequency domain used a 120 ms window that encompassed (had onset with) all of the late potential, but the mean value was first subtracted to eliminate a direct current component. High frequency spectral areas (60 to 120 Hz) and the percent high frequency (100 x [60 to 120 Hz/0 to 120 Hz]) were calculated. Results in both temporal and frequency domains were similar in control patients with coronary artery disease and normal subjects. Patients with ventricular tachycardia had a longer high frequency QRS complex (p less than 0.0001) and longer high frequency terminal signals less than 40 microV (p less than 0.0004), but not significantly lower voltage in the last 40 ms. The most useful temporal domain measurement was high frequency QRS duration (if greater than or equal to 120 ms, odds ratio = 8.2). Patients with ventricular tachycardia had increased high frequency spectral areas (p less than 0.0002) in the late potential, and the percent high frequency was especially increased (p = 0.0000; if percent high frequency greater than 3.1%, odds ratio = 18.4). The odds ratio and the area under the receiver operating characteristic curve were both greater for percent high frequency than for high frequency QRS duration (p less than 0.03). All patients with ventricular tachycardia had a high frequency QRS complex greater than or equal to 107 ms or percent high frequency greater than or equal to 3.1% (sensitivity 100%). For a high frequency QRS complex greater than or equal to 107 ms and percent high frequency greater than or equal to 3.1%, specificity was 96%. Therefore, high frequencies in late potentials, not their duration or reduced voltage, most usefully identify patients with coronary artery disease who are prone to ventricular tachycardia. PMID- 2584564 TI - Spectral and temporal interrogation of signal-averaged electrocardiograms: the best is yet to come. PMID- 2584565 TI - Programmed ventricular stimulation in patients with left ventricular dysfunction and ventricular tachycardia: effects of acute hemodynamic improvement due to nitroprusside. AB - To assess the electrophysiologic effects of acute hemodynamic improvement in patients with left ventricular systolic dysfunction, 12 patients with a left ventricular ejection fraction less than 0.40 and a history of sustained monomorphic ventricular tachycardia were studied. All patients had underlying coronary artery disease. Patients underwent programmed cardiac stimulation in random order during a baseline period and with nitroprusside infusion. Mean pulmonary capillary wedge pressure decreased from 20 +/- 8 mm Hg at baseline study to 8 +/- 3 mm Hg during nitroprusside infusion (p less than 0.0001). Pulmonary artery, right atrial and systemic arterial pressures also decreased with nitroprusside (p less than 0.01). Cardiac output did not change. Left ventricular dimensions, determined by two-dimensional echocardiography, decreased significantly during nitroprusside infusion. The right ventricular effective refractory period, measured during ventricular drive trains at cycle lengths of 400 and 600 ms, were similar during baseline and nitroprusside periods (271 +/- 30 versus 274 +/- 31 ms at 600 ms, and 249 +/- 25 versus 246 +/- 18 ms at 400 ms). In 2 patients no ventricular arrhythmias were induced during either study period; in the other 10, ventricular tachyarrhythmias were induced during both periods. The mean number of extrastimuli required to induce a ventricular tachyarrhythmia was similar during the baseline period (1.8 +/- 0.6) and during nitroprusside infusion (1.9 +/- 0.7). As well, the mean cycle length of ventricular tachycardia induced was similar during the baseline period (347 +/- 61 ms) and during nitroprusside infusion (342 +/- 70 ms).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584566 TI - The feasibility of utilizing the systolic pre-ejection interval as a determinant of pacing rate. AB - Rate-modulated pacing modes adjust the stimulus rate by responding to sensed alterations in physiologic indexes of metabolic demand. This study was designed to determine whether right ventricular pre-ejection interval, measured in patients by a prototype pacemaker system capable of tracking intraventricular volume, changes predictably with exercise and, if so, whether it can be used in an algorithm to vary heart rate appropriately. This system utilizes intraventricular electrical impedance measurements of injected microampere currents to determine intracavitary volume changes. Five pacemaker-dependent patients underwent temporary insertion of a tripolar electrode connected to an external device that sensed cardiac signals, generated an impedance wave form and produced stimuli at rates dependent on pre-ejection interval. Pre-ejection interval did not change as a result of variations in pacing rate itself (347 +/- 41 ms at 70 beats/min versus 321 +/- 19 ms at 130 beats/min), but consistently decreased during graded exercise (by 23% from baseline). During rate-modulated pacing based on pre-ejection interval, heart rate significantly increased during exercise compared with ventricular demand pacing (by 46 +/- 6 versus 7 +/- 6 beats/min, respectively), and increased appropriately during burst exercise. Thus, the pre-ejection interval appears to be a specific, reliable physiologic determinant of pacing rate during exertion, which may be applicable in implantable rate-modulated pacemakers. PMID- 2584567 TI - Amiodarone in chronic heart failure. PMID- 2584568 TI - Surgical therapy for atrial tachycardia in adults. AB - Eighteen adult patients with atrial tachycardia refractory to treatment with a mean of four drugs underwent attempted surgical cure. Atrial tachycardia originated in the right atrium in 17 patients and the left atrium in 1 patient. Tachycardia could be reproducibly induced and terminated by atrial extrastimuli or atrial pacing in 8 patients (44%). Resection of the arrhythmogenic area was performed in 16 patients (89%), and an isolation procedure was performed in 1 patient. In seven cases (39%), the area of isolation or excision included the sinoatrial node. One patient underwent His bundle section because the arrhythmogenic region was too close to the atrioventricular (AV) conduction system to enable resection. The mean duration of clinical follow-up was 56 +/- 34 months. Clinical tachycardia recurred in five patients (28%), but in two patients it did not recur until greater than 1 year after surgery. A permanent pacemaker was implanted in 3 (18%) of the 17 patients whose His-Purkinje system was left intact. One other patient had required permanent pacing before surgery. Only one of the seven patients undergoing sinoatrial node resection or isolation required permanent pacing for symptomatic bradycardia. Apart from the requirement for permanent pacing, no significant complications occurred. Surgical therapy for atrial tachycardia is a safe procedure, but the rate of cure appears to be less than that of supraventricular tachycardias associated with accessory AV connections. Excision or isolation of the sinoatrial node does not necessitate permanent pacing in most patients. PMID- 2584569 TI - Atrial tachycardia: a rare disease sheds light on common questions. PMID- 2584570 TI - Effect of ischemia and postischemic dysfunction on myocardial uptake of technetium-99m-labeled methoxyisobutyl isonitrile and thallium-201. AB - The myocardial uptake of a new technetium-99m-labeled myocardial perfusion agent, methoxyisobutyl isonitrile (Tc-99m MIBI), and thallium-201 was correlated with microsphere flow in an open chest canine model of low coronary flow and postischemic dysfunction. Eighteen dogs were given an injection of thallium-201 (0.5 mCi) and Tc-99m MIBI (5 mCi) either after 40 min of partial left anterior descending artery occlusion (Group I, 10 dogs) or during reperfusion after 15 min of left anterior descending artery occlusion (Group II, 8 dogs). Regional dysfunction was documented during injection in both groups by quantitative two dimensional echocardiography. Regional blood flow was assessed by radiolabeled microspheres. The heart was excised 15 min after radionuclide injection and the left ventricle divided into 96 segments for gamma well counting. Among Group I dogs, central ischemic thallium-201 and Tc-99m MIBI activity (expressed as a percent of the activity in the corresponding nonischemic zone) was comparable, respectively, for endocardial (54 +/- 17% and 52 +/- 17%), mid-wall (71 +/- 20% and 69 +/- 17%) and epicardial (89 +/- 13% and 94 +/- 9%) segments and increased proportionally with flow. There was a good linear correlation among these endocardial segments between flow and both thallium-201 (r = 0.78) and Tc-99m MIBI (r = 0.85) activity. Among Group II dogs, central ischemic endocardial flow (59 +/- 14%) was comparable to thallium-201 (70 +/- 18%) and Tc-99m MIBI (74 +/- 12%) activity. Similarly, relative endocardial flow in the intermediate ischemic region (71 +/- 11%) was comparable to thallium-201 (77 +/- 11%) and Tc-99m MIBI (81 +/- 10%) activity. Thus, myocardial uptake of Tc-99m MIBI and thallium-201 is comparable under conditions of low coronary flow and postischemic dysfunction and closely parallels flow alterations. PMID- 2584571 TI - Indomethacin attenuates the constriction of canine epicardial coronary arteries to acetylcholine in the absence of endothelium: contribution of platelets to vasoconstriction in vivo. AB - This study was designed to evaluate the in vivo effect of acetylcholine on endothelial-damaged canine epicardial coronary arteries and the potential contribution of platelets to those acetylcholine-induced responses. Changes in left anterior descending artery cross-sectional area were determined by quantitative angiography in the closed chest anesthetized dog. Baseline cross sectional area of the left anterior descending artery was not changed by removal of the endothelium by balloon-tipped catheter. Increased constrictor tone produced by prostaglandin F2 alpha was comparable in endothelium-intact and endothelium-removed vessels, supporting an endothelium-independent mechanism for prostaglandin F2 alpha in vivo. Acetylcholine produced anterior descending artery vasodilation with the endothelium intact; a comparable maximal dilator response was also obtained in the presence of increased constrictor tone (prostaglandin F2 alpha). In contrast, acetylcholine produced vasoconstriction of the anterior descending artery when the endothelium was removed. To evaluate the mechanism of acetylcholine-induced vasoconstriction in endothelium-removed vessels, the same protocol was completed in the presence of the platelet inhibitor indomethacin. Indomethacin did not alter baseline cross-sectional area or the dilator response to acetylcholine in endothelium-intact vessels. In contrast, the constrictor response in endothelium-removed vessels was antagonized, and a dilator response comparable with that in endothelium-intact vessels was produced by acetylcholine. The results of this study provide an experimental basis for the observations in human studies in which apparently atherosclerotic vessels constrict in response to acetylcholine. Removal of the endothelium in vivo abolishes the dilator response to acetylcholine and converts the acetylcholine response to vasoconstriction or vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584572 TI - Neutrophil depletion fails to modify myocardial no reflow and functional recovery after coronary reperfusion. AB - Recent studies suggest that neutrophil accumulation and activation in postischemic myocardium may be responsible for myocardial no reflow, which is characterized by an incomplete restoration of blood flow after reperfusion. To examine this further, 11 open chest, anesthetized dogs received bolus injections of a bovine neutrophil antiserum that produced an average 81 +/- 5% depletion of circulating neutrophils, and 10 control dogs received nonimmune serum. Each animal underwent 2 h of left circumflex artery occlusion followed by 4 h of reperfusion. Simultaneous two-dimensional echocardiography and radioactive microsphere blood flow studies were performed at baseline, 2 h of occlusion and early (approximately 5 min) and 4 h of reperfusion. During occlusion, both groups developed similar reductions in myocardial blood flow and levels of ischemic zone myocardial wall thinning. At early reperfusion, similar levels of hyperemia and regional hypokinesia were observed for both groups. By late reperfusion, both groups experienced significant no reflow in the subendocardium (p less than 0.05) and reduced reflow in the mid-myocardium. Regional depression in ischemic zone function persisted throughout the reperfusion period in both groups. However, infarct size expressed as a percent of left ventricular weight, assessed by triphenyltetrazolium chloride staining, was smaller for the neutrophil depletion group compared with the control group (8.7 +/- 1.3% versus 13.1 +/- 1.8%, p less than 0.05). It is concluded that an 81% neutrophil depletion fails to modify the no reflow phenomenon or improve functional recovery after 2 h of coronary artery occlusion and 4 h of coronary reperfusion despite modification of the ultimate size of necrosis. PMID- 2584574 TI - Guidelines for clinical intracardiac electrophysiologic studies. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee to Assess Clinical Intracardiac Electrophysiologic Studies). PMID- 2584573 TI - No reflow revisited. PMID- 2584575 TI - Expert witness testimony. PMID- 2584576 TI - Webster v Reproductive Health Services. PMID- 2584577 TI - Women and crack addiction. PMID- 2584579 TI - Strengthening the network. PMID- 2584578 TI - The legacy of the gifted teacher. PMID- 2584580 TI - Female graduates of a predominantly black college of medicine: their characteristics and challenges. AB - To obtain detailed information about the general characteristics of and the special challenges faced by its predominantly black female graduates. Howard University College of Medicine included an oversampling of women in an extensive 1985-1986 follow-up survey of alumni. Women were asked specific questions about their experiences as women medical students and physicians. Comparative results for the 168 female and 560 male respondents show interesting similarities and differences. Male and female respondents serve the same large proportion of black and female patients, while a higher proportion of the women practice in large cities, provide primary care, and serve younger and poorer patients. Special challenges of being women in medicine include lack of support from faculty, spouses, and colleagues, especially in the areas of child rearing and household management. Although comparisons of earlier (1924-1969) and later (1970-1980) women graduates reveal some improvements, findings include a continuing need to eliminate the dual problems of sexism and racism that have historically faced black women medical students and physicians. Suggestions for continued improvement include support groups, consciousness raising activities, and further research related to women in medicine. PMID- 2584581 TI - Child care choices of women physicians. AB - The majority of women physicians will have children, and they will also shoulder the major responsibility for child care arrangements, in spite of immense professional responsibilities. To date, little information has been made available regarding the child care choices of women physicians. This article summarizes the results of a national survey of women physicians' child care choices. PMID- 2584583 TI - The environment and the eye. PMID- 2584582 TI - Women in medical leadership. PMID- 2584584 TI - Research in optometric practice. PMID- 2584585 TI - Stop the world! I want to get off! PMID- 2584586 TI - Masking of astigmatism with selected spherical soft contact lenses. AB - This observational study investigated the ability of three current brands of spherical soft contact lenses to correct or "mask" low amounts of refractive astigmatism. The lens brands were worn by 16 subjects having at least 0.50 D, but not more than 1.00 D, of refractive astigmatism. Spherocylindrical refraction over the soft lenses was used to determine the amount of astigmatism that was masked by the lenses. Results showed that the wearing of spherical soft contact lenses, such as those used in this study, cannot be expected to predictably mask astigmatism. PMID- 2584587 TI - pH consistency and stability of contact lens solutions. AB - The pH of contact lens solutions has been implicated in the comfort of contact lenses on insertion. The pH of five samples each of 11 different products available for the rinsing and wetting of contact lenses was measured over a 4 month period. Buffered solutions were initially neutral to slightly basic (mean pH 7.03-7.83) and remained relatively close to their original pH throughout the study. The unbuffered solutions tested were initially acidic (5.81 and 5.46). One unbuffered solution rapidly became even more acidic (5.01) before rebounding slightly toward its original value. The difference in the mean pH between all the buffered solutions and the unbuffered solutions was found to be statistically significant. This study indicates the use of buffered solutions unless otherwise contraindicated. PMID- 2584588 TI - Association of antibody titer and chorioretinal scarring in toxoplasmosis retinochoroiditis. AB - Thirty subjects with clinically diagnosed toxoplasmosis retinal lesions, and 30 control subjects matched for age, sex, and race, were evaluated for the presence of IgG antitoxoplasmosis antibodies by enzyme-linked immunosorbent assay (ELISA) methodology. Positive titer was found in 56% of subjects and 20% of controls. Positivity of titer was not correlated to location of lesion, laterality, presence of satellites, sex, or race. Increasing age in both subjects and controls was weakly correlated to positive titer. Study results indicate that a relative overdiagnosis of toxoplasmosis occurs if positive antibody titer is accepted as criteria for positive diagnosis. Currently employed criteria based on physical findings appear to be of little value in predicting positive titer. PMID- 2584589 TI - Wallenberg's syndrome: a first-person account. AB - As clinicians, we may be faced with the patient who has had a stroke with resultant visual and ocular manifestations. Often it is difficult to appreciate the implications of the symptoms and their effects on the quality of life. In this article the first author describes his experiences as a patient, with the hope that this account will assist others to understand this condition better, thus resulting in both enhanced care and sensitivity. PMID- 2584590 TI - A case of Wallenberg's syndrome: ocular motor abnormalities. AB - Eye movements were measured objectively in a patient with Wallenberg's syndrome during the course of his 2-year recovery period. The patient exhibited a change in fixational and reading eye movement patterns consistent with concurrent reduction in symptoms. The results demonstrate the importance of clinical eye movement recordings in such patients to understand more fully the relationship between the visually related symptoms and the objective oculomotor correlates. PMID- 2584592 TI - Dosage cost analysis in glaucoma management. AB - After the diagnosis of chronic open-angle glaucoma has been made, and the indications vs. contraindications of each of the potential first-line topical medications have been weighed, what medical therapy should be initiated if the most cost effective form of management is desired? We surveyed 40 pharmacies in four cities and found no statistical difference between the mean annual cost of therapy with timolol maleate (Timoptic), betaxolol (Betoptic), and pilocarpine. Statistically, both dipivefrin (Propine) and levobunolol (Betagan) were found to be more expensive. We also discovered that there are large variations in medication prices between various pharmacies. In order to enhance compliance, optometrists may want to know the pharmacies in their communities that offer antiglaucoma medications at reasonable prices. PMID- 2584591 TI - Thalasselis' syndrome and other theories on keratoconus. AB - The etiology of keratoconus is still unclear. This study presents a new clinical sign, Thalasselis' syndrome, defined as: an association between keratoconus, magnesium deficiency, type-A behavior and allergy. Also, it introduces the hypothesis that magnesium deficiency could affect pathologically the osmotic mechanism of the cornea, specifically the Na-K and/or Ca-ATPase pumps; the collagen structure by alteration of the adenylate cyclase activity; and other mechanisms as well. Furthermore, we propose the Thalasselis' syndrome is compatible with previous theories on keratoconus. In addition to the other therapeutic measures, such as contact lenses and keratoplasty, this study suggests a clinical, nutritional, psychological, and immunological treatment for keratoconic patients. PMID- 2584593 TI - The questions and curiosity of the psychoanalyst. AB - Questions the analyst asks of the patient are a powerful but neglected aspect of the theory of psychoanalytic technique. Their importance resides in their dynamic impact on the psychic equilibrium of the patient because of their ability to destabilize existing compromise formations. A clinical vignette illustrates the view that the linguistic shift from other modes of discourse to the spoken question heralds a less visible parallel shift in the psychic equilibrium of either the psychoanalyst or patient. There is no more and no less complexity to questions than to any other communication by either analyst or patient. For that reason there can be no systematic classification of questions in the clinical psychoanalytic situation, just as there can be no definitive taxonomy of psychoanalytic discourse. It makes no sense to reduce the enormous diversity and range of all the questions the analyst asks to the simple dichotomy of good or bad for the analysis. Questions are the emblem of the analyst's mode of inquiry; they can further the development of self-observation, which is such an important concomitant, cause, and consequence of structural change. PMID- 2584594 TI - The development of the ego: biological and environmental specificity in the psychopathological developmental process and the selection and construction of ego defenses. AB - This paper suggests that differences in early sensory processing, integration, and differentiation, contribute, in highly specific ways, to characteristics of the ego, deficits in ego functions, and the ego's tendency to employ certain defenses (when certain pathogenic environmental experiences are present). Specifically (1) auditory-verbal-affective vulnerabilities may be associated with disorders of thought and obsessive-compulsive patterns, especially when coupled with environments that tend to confuse affective meanings at behavioral-gestural and symbolic levels; (2) visual-spatial-affective vulnerabilities may be associated with disorders of affect regulation and hysterical patterns, especially when coupled with environments that lack empathy and/or limit setting; (3) spatial, motor movement (vestibular) vulnerabilities may be associated with phobic and/or counterphobic tendencies. The author contends that these hypotheses are sufficiently specific and testable to lead to new research opportunities. PMID- 2584595 TI - Changing psychic structure through treatment: criteria for change. AB - The author outlines his clinical observations during the "middle game" of psychoanalysis, leading to recognition that structural change is taking place. "Middle game," "structure," process, and content are defined and critically discussed. Illustrative clinical vignettes are offered. The presentation emphasizes the importance of an active and resolving transference "struggle"; in addition, more traditionally noted criteria are briefly touched on, e.g., development of observing ego and treatment alliance, changes in dream function and communication, and the reviewing of the neurosis and transference during the termination phase as instances of mourning and working through. The concept of optimal psychobiological function in the service of a homeostatic principle is discussed. PMID- 2584596 TI - Character, character type, and character organization. AB - This paper explores the relevance of the concept of character organization for psychoanalysis and argues for its usefulness in preserving what is specific to character. Character organization is viewed as a bridge concept between the observable and the structural, the role of fantasy and object relations in development, and as a convenient way of describing certain global phenomena not easily encompassed by the structural theory or compromise formation. PMID- 2584597 TI - Negative oedipal transference of a male patient to his female analyst during the termination phase. AB - There has been some debate in the literature concerning the ability of the male patient to experience his paternal, and particularly negative oedipal, transference feelings directly toward his female analyst. In this context, the author describes paternal transference manifestations evident throughout her male patient's analysis, and presents detailed process material from the termination phase. At this time the patient's obsessional neurosis was revived in the context of setting a termination date, and transference to the negative oedipal father could be clearly demonstrated. The paper illustrates that even the negative oedipal component of the paternal transference can be experienced directly in the male patient/female analyst, dyad, and interpretation of this material can bring it into clearer focus. The author discusses some possible influences of her sex on the timing and intensity of the material. PMID- 2584598 TI - Dream frequency in psychoanalysis and psychoanalytic psychotherapy. AB - The authors examine data on dream frequency from 50 patients, half of whom were seen in psychoanalysis and half in psychoanalytic psychotherapy. Frequency, defined as the proportion of sessions where at least one dream is related, is analyzed statistically as a function of sex, age, and type of treatment. Also, treatment outcome is examined as a function of sex, type of treatment, diagnosis, and dream frequency. Psychoanalytic patients are found to have higher dream frequency than the patients in the psychotherapy group. Higher average dream frequency is correlated with a better treatment outcome in both patient groups. PMID- 2584599 TI - Spelunking as a manifestation of a counterclaustrophobia. AB - Material is presented from the case history of a patient whose interest in spelunking (cave exploration) was found to be an unconscious expression of a type of counterclaustrophobia. Both oedipal and preoedipal determinants of the claustrophobic anxieties are delineated. Of particular note in this instance is the testicular element in the genesis of the patient's claustrophobia. His confusion of the movements of his testicles into his inguinal canals during childhood defecation with the movements of the feces themselves lent an special intensity to his fear of being flushed away from the mother by an expulsive anal birth from the claustrum. Childhood anxiety aroused when his testicles would become trapped in the inguinal canals was an important forerunner of the adult fear of being trapped in confined spaces. A counterphobic element of the spelunking per se was his enjoyment in hanging suspended by a rope in caves. In this manner, he was able to act out (by virtue of his body-testicle equation) his identification with, and control over, the disappearing testicles in the setting of a claustrophilic union with the mother. PMID- 2584600 TI - Aliens among us: a representation of children in science fiction. AB - As a literary genre, science fiction has been largely ignored by psychoanalysis. Science fiction lends itself well to analytic interpretations since its structure embraces an attitude of "cognitive estrangement" (a term that defines the genre). Science fiction allows for the exploration of new and different permutations of seemingly ageless conflicts and concerns. One of the conflicts science fiction seems to address revolves about our fears regarding our children. These children become the "aliens" among us, as they seek to usurp parental power and authority. This issue is addressed through a study of two of Ray Bradbury's short stories. By manipulating the reader's experience of the "uncanny," Bradbury succeeds in tapping what appear to be prevalent and potent fears regarding children and, reflexively, the adults who produce them. Mechanisms involved in this play on "alienness" include projective identification of destructive aspects of the self, a resurgence of archaic superego forerunners constituted around primal scene material, and a reawakening of oedipal struggles. PMID- 2584601 TI - Uses and limitations of Kohut's self psychology in the treatment of borderline patients. AB - The treatment of borderline patients provides a setting in which the analyst can evaluate the clinical usefulness of Kohut's theories. The issues that arise in this treatment can also highlight aspects of Kohut's theories that are incomplete and require other theoretical models in order to understand the patient optimally. PMID- 2584603 TI - Personal reflections on the role of sexuality in the etiology and treatment of the neuroses. Panel Report. PMID- 2584602 TI - Current concepts of the development of sexuality. Panel Report. PMID- 2584604 TI - Evaluation of outcome of psychoanalytic treatment: should followup by the analyst be part of the post-termination phase of analytic treatment? Panel Report. PMID- 2584605 TI - Unconscious fantasy. Panel Report. PMID- 2584606 TI - Protein binding to nitrocellulose, nylon and PVDF membranes in immunoassays and electroblotting. AB - A selection of different membranes commonly used to bind proteins in blotting and dot binding assays were investigated for a range of properties which would influence their performance. Large differences were observed in the membranes' ability to bind increasing amounts of protein, the effect of incubation times on the quantity of protein bound and the loss of proteins from the membranes following their incubation with different detergents or protein blocking agents. These differences could only partially explain the observed performance of the membranes when used as protein adsorbants in immunoassays and when different buffers were used for the electro-transfer of several different proteins to a range of membranes. PMID- 2584607 TI - Evaluation and practical aspects of the use of a commercial DNA probe for detection of mycoplasma infections in cell cultures. AB - Cell cultures have been analyzed for mycoplasma infections by using a commercial DNA-probe based on rRNA genes from mycoplasmas. Both the original version, Mycoplasma T.C. Detection Kit, and the improved version of the kit, Mycoplasma T.C. II Rapid Detection System, were used. The sensitivities of the two tests were found to be adequate in most cases and the improved version of the kit was 10-100 times more sensitive than the original one. A batch variation was observed with the improved version, which is not satisfactory. This batch variation can, however, be checked and the performance of the method with a properly working lot was found to be good. PMID- 2584608 TI - Quantitative determination of pectic substances as an example of a rhamnopolysaccharide assay. AB - A quantitative enzymatic assay for rhamnopolysaccharides is described. The procedure is shown with pectic substances as an example. The test is based on the enzymatic degradation of the macromolecules to liberate L-rhamnose. This sugar can be quantitatively determined with the help of L-rhamnose dehydrogenase under concomitant reduction of NAD, thus allowing the quantitative evaluation of the original pectin. PMID- 2584609 TI - Pilot scale production of a human monoclonal antibody against human immunodeficiency virus HIV-1. AB - Human monoclonal antibodies against the transmembrane protein gp41 of HIV-1 were isolated and purified on a pilot scale. A purification scheme was established for the production of human monoclonal antibodies on the gram scale. 50 1 of culture supernatant can be treated in one purification cycle. The hybridomas were mass cultured in an airlift fermenter. The culture broth was clarified by microfiltration and chromatographed on CM-Sepharose fast flow and protein A Superose. Scale up of the high performance affinity chromatography from 1 ml protein A Superose up to 40 ml is described. All desalting steps were performed by gel filtration on Sephadex G-25 coarse. The yield of the whole purification procedure is in the range of 50-60%. The purity is higher than 99.9%. DNA and reverse transcriptase could not be detected. The whole method is designed as a basis for scale up to industrial scale. Results from quality control assays have proven the validity of this approach. PMID- 2584611 TI - The location of extrinsic efferent and afferent nerve cell bodies of the normal canine stomach. AB - The location of the extrinsic efferent and afferent nerve cell bodies to the mucosa, submucosa, and tunica muscularis of the cardiac, gastric, and pyloric gland regions of the ventral stomach and to the mucosa-submucosa alone of these 3 glandular gastric regions was determined using the horseradish peroxidase technique. All animals of the study demonstrated labeling bilaterally in the rostrocaudal extent of the dorsal motor nucleus of the vagus nerve (DMV) although mucosa-submucosa injections resulted in fewer labeled cells in the DMV. There was no evidence of viscerotopic organization within the DMV for the different gastric regions. However, the left nucleus generally contained a greater number of labeled cells than the right nucleus. Injection of the mucosa, submucosa, and tunica muscularis of the cardiac gland region also resulted in labeling in the nucleus ambiguus in 4 of 5 animals. The vast majority of labeled postganglionic sympathetic neurons were found in the celiacomesenteric ganglion. Labeled cells were also located variously in the stellate ganglion, middle cervical ganglion, and sympathetic trunk ganglia for the different groups. There was no discernible pattern of localization of labeled cells within a sympathetic ganglion. For the stomach, afferent labeled cells were located in the range of the first thoracic to fourth lumbar spinal ganglia and the nodose ganglia, bilaterally. As with sympathetic neurons, there was no discernible pattern of localization of labeled cells within a sensory ganglion. PMID- 2584610 TI - Microcalorimetric detection of sucrose admixture in glucose samples. PMID- 2584612 TI - Autonomic nervous stimulation affects left ventricular relaxation more than left ventricular contraction. AB - We studied the effects of stimulation of the vagal and also the sympathetic efferent cardiac nerves on left ventricular (LV) relaxation and contraction in 11 anesthetized, open-chest dogs. In each dog, we paced the ventricles at a fixed rate of 120 beats.min-1 and kept the systemic arterial pressure constant. The maximum rate of LV pressure decline, (dP/dt)min, and the time constant of LV isovolumic pressure decline, tau, were used as our indexes of LV relaxation. The maximum rate of LV pressure rise, (dP/dt)max, was used as our measure of LV contractility. Vagal stimulation decreased (dP/dt)min more than (dP/dt)max (P less than 0.01) when examined at frequencies that ranged from 2 to 12 Hz. Vagal stimulation at 12 Hz reduced (dP/dt)min by 26% (P less than 0.001) and increased tau by 57% (P less than 0.0001) but decreased (dP/dt)max by only 20%. Sympathetic stimulation, at frequencies that ranged from 2 to 12 Hz, increased (dP/dt)min more than (dP/dt)max (P less than 0.001). Sympathetic stimulation at 12 Hz increased (dP/dt)min by 130% (P less than 0.0001) whereas it increased (dP/dt)max by 60% (P less than 0.0001). Sympathetic stimulation at 12 Hz decreased tau by 74% (P less than 0.0001). Our studies suggest that cardiac autonomic nerve stimulation affects left ventricular relaxation more than left ventricular contraction. PMID- 2584613 TI - Cardiovascular responses to 5-HT in the ventrolateral medulla of the rat. AB - Bilateral microinjection of 5-HT into the rostral ventrolateral medulla (RVLM) produced a fall in blood pressure in anaesthetised rats. Injection of 10-20 nmol 5-HT produced a fall in mean arterial pressure of 5-55 (mean 15.7) mm Hg which lasted 1-69 (mean 25.2) min. Larger doses (up to 120 nmol) produced a similar, but longer lasting fall in pressure. The depressor response was accompanied by bradycardia but tachycardia was sometimes seen in response to injections made at the rostral tip of the RVLM. An analysis of haemodynamic changes in response to 40-50 nmol 5-HT showed the depressor response was accompanied by an increase in vascular conductance of hindlimb muscle (20-200, mean 87.2%) and a rise of 2-9 (mean 5.9)degrees C, in the surface temperature of the tail. In contrast, an increase in renal vascular conductance (8-66 (mean 19.6)%) was only evoked after injections of 5-HT into the caudal half of the RVLM whereas a decrease in conductance (14-48 (mean 24.5)%) was measured after injections of 5-HT into the rostral tip of the nucleus. The hindlimb muscle and tail vascular beds therefore appear to make a larger contribution to the fall in peripheral resistance than the renal bed. PMID- 2584614 TI - Prolongation of cardiac cycle length attenuates negative dromotropic response to selective vagal stimuli. AB - We stimulated intracardiac parasympathetic nerve fibers that selectively innervated the atrioventricular (AV) nodal area (AV parasympathetic stimulation), and the sinoatrial (SA) nodal area (SA parasympathetic stimulation), in autonomically decentralized, anesthetized dogs. We then compared these responses to those elicited by stimulation of the cervical vagus nerves. We investigated the interactions between the dromotropic and chronotropic responses to simultaneous AV and SA parasympathetic stimulation. AV parasympathetic stimulation increased the AV interval (AV conduction time) but did not alter the interval between atrial depolarizations (sinus cycle length). SA parasympathetic stimulation increased the sinus cycle length and evoked small changes in the AV interval. Simultaneous AV and SA parasympathetic stimulation, at different combinations of frequencies, induced negative dromotropic and chronotropic responses that were similar to those evoked by cervical vagal stimulation. The greater the increase in sinus cycle length, the less did a given parasympathetic stimulation prolong the AV interval. The prolongation of the AV interval by parasympathetic stimulation did not affect the sinus cycle length. These results suggest that the direct pure negative dromotropic response to parasympathetic nerve stimulation is attenuated by the prolongation of the sinus cycle length, e.g. a concomitant negative chronotropic effect of the parasympathetic stimulation, in the dog heart. This attenuation reflects a mechanism that does not depend on the relative timing of the stimulus impulses in the cardiac cycle, i.e. a phase-independent, as well as the previously reported phase-dependent, mechanism. PMID- 2584616 TI - [3H]-alpha, beta-methylene ATP, a radioligand labelling P2-purinoceptors. PMID- 2584617 TI - Uptake of [3H]dopamine in the mouse adrenal medulla during dark and light period. AB - Uptake of exogenous [3H]dopamine in adrenal chromaffin cells of the mouse was studied by autoradiography under a 12-h light, 12-h dark cycle. The uptake of [3H]dopamine in adrenal chromaffin cells was markedly decreased in the dark period. The decrease was prevented by adrenal denervation. It is postulated that there is a neurally mediated suppression of [3H]dopamine uptake by adrenal chromaffin cells in the dark period. Adrenaline-storing (A) cells are more sensitive to the decreased sympathetic activity than noradrenaline-storing (NA) cells while increased sympathetic activity non-selectively affects both types of adrenal chromaffin cells. PMID- 2584615 TI - Renal sympathetic responses to changes in arterial pressure in conscious rabbits. AB - Renal sympathetic nerve activity (RSNA) at rest and in response to changes in mean arterial pressure (MAP) were examined by measuring norepinephrine (NE) spillover rate across the kidney in 14 conscious rabbits. NE spillover rate was calculated from veno-arterial difference in plasma NE concentrations across the kidney corrected by the fractional extraction of infused tritiated NE. Renal NE spillover rate (mean +/- S.E.M.) at rest in 14 conscious rabbits was 14.7 +/- 0.9 ng/min. During sodium nitroprusside infusions at 10 and 20 micrograms/kg/min, renal NE spillover rate significantly increased by 55 and 101% in response to falls in MAP of 15 and 19% respectively. During phenylephrine infusion at 2 micrograms/kg/min, renal NE spillover rate significantly decreased by 40% in response to a 14% rise in MAP. The relative contribution of renal to total NE spillover rate decreased during sympathetic stimulation, while this ratio was unchanged during sympathetic inhibition. This study demonstrates that the renal NE spillover method is sufficiently sensitive and reliable to detect the responses in RSNA to physiological stimuli in conscious rabbits. The difference observed in the degree of stimulation of renal versus total NE spillover rate during hypotension produces confirmation that sympathetic responses are not uniformly distributed in the body. PMID- 2584618 TI - Plantar fascia is a frequent source of pathology within the lower extremity. PMID- 2584619 TI - Crescentic transmalleolar osteotomy for optimal exposure of the medial talar dome. AB - A review of the literature suggests that surgical treatment of transchondral talar dome fractures affords superior results over lengthy conservative therapy. Medial lesions have been reported most often. The authors perform stress views in acute and chronic ankle injuries, as there are often associated ligament ruptures with suspected talar dome fractures, and routinely use an air-contrast radiographic technique for visualization of the continuity of the articular cartilage. An arthrogram is performed for definitive diagnosis of ligamentous injury. A new osseous surgical approach to the medial talar dome has been presented, entailing a crescentic osteotomy of the medial malleolus. The distinct advantage has proven to be enhanced exposure to the middle and posterior aspects of the medial margin of the talus. The configuration of the crescentic osteotomy is also amenable to internal fixation and tension band wiring has been recommended. Unrestricted access to the site of a medial transchondral talar dome fracture through this osteotomy is the benefit of a technically well-performed procedure. PMID- 2584620 TI - Undifferentiated primary malignant soft tissue tumor. AB - A rare case of a malignant, undifferentiated, soft tissue neoplasm is presented. A thorough podiatric and medical evaluation is essential in the proper diagnosis and treatment of soft tissue tumors. This evaluation includes appropriate consultation with the various medical specialists. PMID- 2584622 TI - Sutter double-stem silicone implant arthroplasty of the lesser metatarsophalangeal joints. AB - A double-stem silicone prosthetic implant to replace the lesser metatarsophalangeal joint has been found to be successful in helping several difficult-to-treat conditions that affect the forefoot. The prosthetic device can be used to replace the proximal phalanx base or the metatarsal head. It is more successful in older (over age 50) patients. PMID- 2584621 TI - Disseminated gonococcal infection involving the foot. AB - The patient had two features of N. gonorrhoeae infection, which were urogenital inflammation and pharyngitis. At first, the urogenital inflammation was denied and so delayed the correct diagnosis. The patient had been treated initially with oral penicillin for the pharyngitis, but without effect. The result was because of the increase in penicillin-resistant strains. This created DGI with initial migratory polyarthralgia from his left shoulder to the right midfoot. Acute arthritis formed in the midfoot. Once the correct diagnosis was made and appropriate antibiotics started, the infection responded rapidly and completely. PMID- 2584623 TI - Avascular necrosis following chevron distal metatarsal osteotomy: a significant risk? AB - The authors have shown the chevron osteotomy to be an effective operation for hallux valgus where degenerative changes have not occurred in the metatarsophalangeal joint. Chevron osteotomy is normally restricted to younger patients, yet in this study there has been no upper limit for age and the authors have shown a high rate of patient satisfaction with good mobility and cosmesis. Results are not significantly operator-dependent, and the procedure is simple and reliable. The authors have been unable to verify previous reports in smaller studies of the serious complication of avascular necrosis of the metatarsal head on clinical or radiological grounds. PMID- 2584625 TI - Schwannoma of the fifth digit. AB - The authors have presented a rare case of benign solitary schwannoma of the fifth digit. A case study involving this digit has not been reported previously. The lesion was simple to excise and provided no postoperative complications. Schwannomas may produce pain, parasthesia, hypesthesia, and occasionally motor and sensory deficits. Because the lesion is a nerve sheath tumor, it usually can be separated from the nerve. Simple excision is recommended because the tumor rarely becomes malignant. The tumor should be diagnosed correctly in order to rule out neurofibromatosis-1, neurofibroma, or malignant schwannoma. This can be performed during biopsy by observing for the presence of Antoni type A or type B cells, and through other distinguishing characteristics, such as encapsulation, singularity of the tumor, and lack of skin pigmentation changes. Benign schwannomas rarely recur. PMID- 2584624 TI - Crossover second toe deformity: etiology and treatment. AB - The pathogenesis, etiology, diagnostic features, and treatment of the crossover second toe deformity are discussed in this manuscript. The crossover second toe deformity is an undescribed entity in podiatric literature. Two cases are presented by the authors to illustrate the deformity and surgical correction. PMID- 2584626 TI - Rupture of the lateral head of the gastrocnemius muscle at the musculotendinous junction mimicking a compartment syndrome. AB - This case report documents an acute rupture of the lateral head of the gastrocnemius muscle at the myotendinous junction and a lateral dislocation of the tibialis anterior tendon with a clinical presentation consistent with a compartment syndrome, despite the intraoperative finding of a rupture of the posterior and lateral compartments. Extensive hematoma formation led to marked edema, paresthesias, muscle weakness, and severe pain in the involved leg. Surgical repair of the torn muscle and dislocated tendon and evacuation of the dissecting hematoma resulted in a well-functioning extremity. The authors emphasize the importance of prompt diagnosis of soft tissue injuries, which may place a patient at risk for a compartment syndrome. A compartment syndrome may lead to severe ischemia and irreversible tissue necrosis if intracompartmental hemorrhage of a torn muscle persists, and may require a surgical decompression. The clinical presentation, as well as adjunctive techniques in the diagnosis of a patient with a partial rupture of the gastrocnemius muscle, and a compartment syndrome, were presented. PMID- 2584627 TI - Osteoid osteoma: report of a case. AB - An osteoid osteoma on the foot diagnosed by clinical, pathologic, and radiographic evaluation was described. The lesion is found predominantly in the long bones of the foot. A differential diagnosis of osteoma, osteoblastoma, and osteogenic sarcoma must be ruled out in order for proper management of the patient. The case of a solitary, bony lesion located at the base of the proximal phalanx of the fifth toe in a 38-year-old, white female was presented. No evidence of malignancy was found. The lesion was a hard, painful, palpable mass, located in the fourth left web space, and was excised completely. The skin defect was closed in order for proper syndactilization of the adjoining fourth and fifth digits. Two years post-operatively, the patient was asymptomatic with no evidence of reoccurrence. PMID- 2584629 TI - Surgical treatment of metatarsus adductus using a combined soft tissue and osseous approach. AB - Children between 6 and 8 years of age with metatarsus adductus deformity have been considered to be in the gray zone for surgical correction. Should osseous or soft tissue procedures be implemented to reduce the adducted attitude of the metatarsals? The literature clearly describes one or the other and the intermediary chondrotomy procedure described by Johnson. The use of a combined approach has not been presented. The present authors offer a brief review of metatarsus adductus, and two case reports using a modified, combined approach. Two 7-year-old girls presented with bilateral resistant metatarsus adductus deformities. The authors contend that the first and fifth metatarsals are the major deforming forces in this age group, and may be corrected with base wedge osteotomies, while the central three metatarsals are more amendable to capsular and ligamentous releases. Advantages of soft tissue procedures on the central rays include avoidance of extensive dissection, creating less trauma and avoidance of the need for internal fixation. The obvious disadvantage is the inability to adequately reduce the deformity. This can be assessed intraoperatively. These authors, therefore, conclude that this modified surgical approach is a viable alternative to the previously described procedures for resistant metatarsus adductus. PMID- 2584628 TI - First metatarsal-cuneiform dorsal exostosis: its anatomical relation with the medial dorsal cutaneous nerve. AB - The results of the cadaver dissection show the importance of identifying the proper digital nerve at the time of surgery. In all 20 cadaver dissections, the nerve crossed the first cuneometatarsal joint. Identification of this nerve, along with meticulous dissection may help prevent the formation of postoperative neuroma. PMID- 2584630 TI - First metatarsocuneiform joint arthrodesis: a five-year retrospective analysis. AB - Historically, first metatarsocuneiform joint arthrodesis has been advocated for severe metatarsus primus adductus deformity and as a salvage procedure in reconstructive forefoot surgery. At the Podiatry Hospital of Pittsburgh, the authors have expanded the use of this procedure to include elimination of excessive motion at the first metatarsocuneiform joint and to restore functional integrity to the first ray in an otherwise poorly functioning foot. First metatarsocuneiform arthrodesis has had poor acceptance by podiatric surgeons. Common reasons for this poor acceptance are technical difficulty associated with the procedure and often-cited complications such as shortening of the first ray, with symptomatic transfer lesions, as well as nonunion of the arthrodesis site. The authors evaluated 54 procedures. Results of first metatarsocuneiform joint arthrodesis for long-term reduction of the intermetatarsal angle and for limiting abnormal motion at this joint have been very good. Few complications were encountered. Shortening of the first metatarsal with secondary transfer lesions was not found to be a common problem. Several radiographic nonunions occurred, none of which were symptomatic. The surgical procedure, as it is performed at the Podiatry Hospital of Pittsburgh, is described. Results from a 5-year retrospective analysis of first metatarsocuneiform arthrodesis are presented. PMID- 2584631 TI - Arthrodesis of the hallux interphalangeal joint using a diagonally placed 2-mm. cortical bone screw. AB - Arthrodesis of the interphalangeal joint of the hallux is quite often needed in conjunction with first metatarsophalangeal joint interpositional arthroplasty. With the exception of two cited techniques, the authors believe all previously described methods of achieving interphalangeal joint arthrodesis are inconsistent in their results and in their ability to be performed in conjunction with first metatarsophalangeal joint procedures. The authors, therefore, sought a more practical, efficacious method of achieving hallux interphalangeal joint arthrodesis in the presence of first metatarsophalangeal joint implants, while still using ASIF-AO compressive technique. Presented is their technique of hallux IPJ arthrodesis using a diagonally placed 2-mm. cortical bone screw. PMID- 2584632 TI - Normal and pathologic anatomy of hallux valgus. AB - The author reviews the pathologic entity of hallux valgus, using anatomic illustrations. Although this description is not considered to represent new information, foot surgeons must continue to appreciate the delicate biomechanical imbalances leading to this anomaly. PMID- 2584633 TI - Spindle cell hemangioendothelioma of the foot. AB - The author suggests an index of suspicion when dealing with recurrent tumors in the foot. Initially, a lesion was removed and pathologic diagnosis was lipoma. Repetitive recurrence lead to the diagnosis of spindle cell hemangioendothelioma. A relationship has been suggested between this lesion and low grade malignancies. PMID- 2584634 TI - Magnetic resonance imaging of the diabetic foot. PMID- 2584635 TI - Are we undertreating our foot and leg problems. PMID- 2584636 TI - Modification of the total first metatarsophalangeal joint implant arthroplasty. PMID- 2584637 TI - Blindness influences the growth of institutionalized prepubertal subjects. AB - To investigate if blindness influences the growth rate of young subjects we measured height and weight of 71 prepubertal blind subjects (33 females and 38 males) aged 7-10 yr, in Tanner stage one puberty, living at the Institute "Martuscelli" for young blind individuals in Naples, Italy. They were divided into two groups: group 1 consisting of 27 subjects (14 females and 13 males) with total blindness; group 2 consisting of 44 subjects (20 females and 24 males) having only a light perception. The distribution in quintiles of their height and weight was compared by X2 test for trend to that of an age-matched large population (7902 subjects: 3808 females and 4094 males) of primary school from the same district. A stature significantly lower than controls was evidenced in both group 1 (p = 0.0006) and in group 2 (p = 0.008). When the comparison is performed taking into account the sex of subjects, the girls of both group 1 (p = 0.0014) and group 2 (p = 0.0004) show a stature significantly lower than female controls, whereas the stature of boys of both groups did not differ from that of male controls. No statistically significant differences in weight distribution were found between controls and either group 1 and group 2. Our results suggest that total or partial blindness could influence negatively the growth of prepubertal subjects; in particular it can cause short stature or growth delay especially in female sex. PMID- 2584638 TI - Effects of surgery and general or epidural anesthesia on plasma levels of cortisol, growth hormone and prolactin in infants under one year of age. AB - Twenty infants under one yr of age undergoing minor surgery were divided in two groups according to the type of anesthesia (epidural, Group 1, n = 10; general, Group 2, n = 10) which was randomly performed. Blood samples for cortisol (F), growth hormone (GH), and prolactin (PRL) determination were taken from each infant in baseline conditions, before surgery, and at the end of surgery. Mean plasma F levels in infants of group 2 rose significantly (p less than 0.01) before surgery to attend a maximum at the end of surgery (p less than 0.005). In infants of Group 1 a significant increase was also observed before surgery (p less than 0.05) but at the end of surgery mean plasma cortisol returned to levels comparable to baseline. Mean GH plasma levels were not significantly affected by both types of anesthesia, however an increase (not statistically significant) was observed at the end of surgery in both groups. Mean plasma PRL levels showed a significant increase before surgery (p less than 0.05 and p less than 0.01 in group 1 and 2, respectively) and a further increase at the end of surgery in both groups of infants (p less than 0.005). These results suggest that in infants under one yr of age both types of anesthetic procedures preceding surgery have no significant effect on plasma GH, but produce a significant increase of cortisol and prolactin mean plasma levels. The cortisol response to surgery and general or epidural anesthesia was similar to that reported in adults and prepubertal boys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584639 TI - Iodine deficiency in schoolchildren of the province of Parma, Italy. PMID- 2584640 TI - Acute scaphoid fracture with scapholunate gap. AB - Disruptive forces from wrist trauma are thought to fracture bone or disrupt ligaments. Two cases are presented to demonstrate the simultaneous occurrence of acute scaphoid fracture and scapholunate gap. Recommended treatment in acute cases is open reduction and internal fixation of the fracture and open stabilization of the scaphoid. In chronic cases, we recommend open reduction and internal fixation with bone graft to the scaphoid nonunion combined with fusion of the scaphoid-trapezium-trapezoid joint. PMID- 2584641 TI - Application of magnetic resonance imaging to ischemic necrosis of the lunate. AB - Twenty patients (22 wrists), in whom ischemic necrosis of the lunate was suspected clinically, were studied prospectively by physical examination, conventional radiography, radionuclide bone scintigraphy, and magnetic resonance imaging. Magnetic resonance imaging showed more specificity than radiography or radionuclide bone imaging in making the diagnosis of ischemic necrosis of the lunate. Two patterns of lunate signal defect were seen on magnetic resonance imaging with focal or generalized signal loss on T1-weighted and T2-weighted images. Generalized loss of lunate signal on T1-weighted images was diagnostic for ischemic necrosis of the lunate. Focal signal loss on the radial one half of the lunate suggested early involvement. Normal or increased signal on the corresponding T2-weighted image implied an earlier stage and a better prognosis. Magnetic resonance imaging evaluation of the lunate may be useful for subclassification of Lichtman's radiographic stage 2 and can be employed to follow lunate revascularization after treatment. Magnetic resonance imaging is a low risk, noninvasive diagnostic technique, which can modify diagnosis, staging, treatment and prognosis of ischemic necrosis of the lunate. PMID- 2584642 TI - Reliability of carpal angle determinations. AB - The radioscaphoid, radiolunate, and radiocapitate angles of nine lateral projections of the wrist (three in flexion, three in extension, and three in neutral position) of three fresh cadaver specimens were measured. Seven orthopedic surgeons (six hand surgeons and one orthopedic surgeon) made the measurements with a standard goniometer using both the axial and tangential methods of angle determination. The overall standard deviation for all measurements was 5.2 degrees, and no significant difference in variability between axial and tangential methods was found. By comparing the same angles from different wrist positions, the amount of flexion-extension motion of the capitate, scaphoid, and lunate with respect to the radius was estimated. To assess the accuracy of such a method of carpal motion determination, a more accurate stereoradiographic method of analysis of carpal kinematics was utilized. The overall estimated error of this standard goniometric method of carpal motion determination averaged 7.4 degrees. PMID- 2584644 TI - Chinese external fixation treatment for fractures of the distal end of the radius. AB - One hundred forty-five patients with fractures of the distal end of the radius (age range, 13 to 76 years; means, 61 years) were treated conservatively with a Chinese system of external fixation. Most of the fractures were of the extension and extraarticular type. The fixation system consists of four splints used in conjunction with three pressure pads and three or four slings. The system was used after successful manipulative reduction, and the patients were instructed to move their joints as soon as possible. The results, especially in elderly patients, were highly encouraging. We believe that this Chinese system of external fixation serves as a kind of functional brace. PMID- 2584643 TI - Primary malignant bone tumors of the hand. AB - Malignant bone tumors of the hand are rare and few centers have extensive experience in the care of patients with these lesions. Eighteen patients with 22 lesions were evaluated at our institution. There were nine chondrosarcomas, four hemangioendothelial sarcomas, two cases each of osteosarcoma and fibrosarcoma, and a single case of Ewing's tumor. The average age of the patients was 39 years. Ten lesions each were located in the metacarpals and phalanges, with two lesions in the carpus. There were nine local recurrences, which appeared at an average of 24.5 months (range, 3 to 74 months). Curettage procedures resulted in the highest rate of local recurrence (85%). Three patients died of metastatic disease. Surgical control of these lesions requires careful preoperative planning and wide surgical margins. Regular oncologic follow-up is necessary. PMID- 2584645 TI - A new method of evaluating angulation of scaphoid nonunions. PMID- 2584646 TI - A rare "tumor" of the wrist. PMID- 2584648 TI - Toxic shock syndrome. PMID- 2584647 TI - Catfish spine envenomation of the hand. PMID- 2584649 TI - Third International Conference on Surgical Rehabilitation of the Upper Limb in Tetraplegia (quadriplegia). PMID- 2584650 TI - Study of upper extremity growth and development using human embryos and computer reconstructed models. AB - This study investigated the apical ectodermal ridge and early vasculature of the human limb bud by use of histologic techniques and a new method of computer modeling. Fourteen human embryos were studied (more than 10,000 sections) microscopically and the embryonic limbs were reconstructed three-dimensionally by use of a serialized programming method. The apical ectodermal ridge consists of an extensive band of specialized cells, located over the rim of the limb surmounting a strip of rapidly-dividing mesenchymal cells. It is consistently supplied by a large vessel that shows extensive central branching. PMID- 2584651 TI - Hand complications in children from digital sucking. AB - Digital sucking is common in children. Although orthodontic complications have been reported, hand complications of digital sucking are seldom described. Five patients are reported; two had digital deformities and three had infections. Deformities of the digits were improved with splinting. Infections required surgical drainage followed by postoperative splint protection to prevent digital sucking. Splinting prohibited sucking in four of five patients. PMID- 2584652 TI - Two-stage correction of thumb adduction contracture in Freeman-Sheldon syndrome (craniocarpotarsal dysplasia). AB - Freeman-Sheldon syndrome is a rare congenital anomaly that is characterized by facial, hand, and foot deformities. We describe a female infant who had severe adduction contractures of the thumbs. A two-stage reconstruction was done. The first web space soft tissues were stretched with a transversely oriented external skeletal distractor, then a conventional first web space deepening and release was performed. PMID- 2584654 TI - Distraction osteogenesis of a congenital amputation at the elbow. AB - A case is described demonstrating the effectiveness of distraction osteogenesis for the lengthening of a short below elbow congenital amputation. To our knowledge this technique has not been previously used in a patient with a congenital amputation. The surgical technique of corticotomy and postoperative lengthening is detailed. The result converted the level of patient performance from elbow disarticulation to functional below elbow status. PMID- 2584653 TI - Improvement in the surgical results of treatment of duplicated thumb by preoperative splinting. AB - Seven patients with an angular deformity of their duplicated thumb were treated by splinting and taping before operation. In all patients, the angular deformity of the interphalangeal joint improved within a few months, and surgical centralization and osteotomy were not necessary. Furthermore the design of the fillet flap was easier and more accurate as was the adjustment of the joint ligament tension. After operation there was no recurrence of angular deformity, and the range of motion of the interphalangeal joint was good. We believe that this procedure simplifies the operative approach, making it more precise and helping to prevent postoperative complications in patients with angular deformity. PMID- 2584655 TI - Functional anatomy of the human digital flexor pulley system. AB - The anatomy of 55 cadaver digits was studied, both statistically and with simulated active motion using weights attached to the flexor tendons. The modified description of Doyle and Blythe accurately described the anatomy observed. Serial pulley sectioning showed two types of bowstringing, both of which affected the relationship of tendon excursion to joint motion. The most constant, resulting in 15% loss of motion for a fixed tendon excursion, occurred over the concave surfaces of the proximal and middle phalanges. Bowstringing at the proximal interphalangeal joint was present only after 30 degrees of flexion had occurred, because of the convexity of the phalangeal condyles. PMID- 2584656 TI - Three rare causes of extensor tendon rupture. AB - Three unusual cases of rupture of finger extensor tendons by attrition are reported. In one instance it was associated with long-standing nonunion of a scaphoid fracture, with a posttraumatic dorsal subluxation of the lower end of the ulna in another, and with a Madelung's deformity in the third. Extensor tendon rupture has not been previously recorded in the English-language literature after the first two conditions. PMID- 2584658 TI - Direct nerve crossing with the intercostal nerve to treat avulsion injuries of the brachial plexus. AB - One hundred seventy-nine patients with root avulsion brachial plexus injuries were treated with direct nerve crossing with the intercostal nerve and 159 cases were followed more than 1 1/2 years after the operation. When suture was done to the musculocutaneous nerve, 90% of 10 children who had operation within 7 months of injury and 81.8% of 110 adults, younger than 40 years with operation within 6 months of injury regained grade 3 or 4 elbow flexion power. This direct method seems to produce better results than those of nerve crossing, which uses intermediary nerve grafts. PMID- 2584659 TI - Perfusion of the abductor digiti quinti after transfer on a neurovascular pedicle. AB - The perfusion to the abductor digiti quinti muscle was measured, both before and after, opponensplasty transfer on its neurovascular pedicle in six monkeys, with use of the hydrogen wash-out technique to determine blood flow. The musculotendinous unit can be transferred without vascular compromise, but detachment of the abductor digiti quinti from its origin on the pisiform results in ischemia. Such impairment of blood flow to the muscle may be responsible for the postoperative fibrosis, which has been seen as a complication of the procedure. PMID- 2584657 TI - Crossed intrinsic transfer. AB - A retrospective analysis of the long-term results of the crossed intrinsic transfer operation is presented. Twenty-one patients (30 hands) with rheumatoid arthritis and one patient (1 hand) with systemic lupus erythematosus were examined clinically and radiographically. The average follow-up was 12.7 years. The average postoperative ulnar drift for all fingers was 5 degrees. The magnitude of ulnar drift did not increase over time. The average active range of motion for the metacarpophalangeal joints was 47 degrees and for the proximal interphalangeal joints it was 58 degrees. The average radial deviation deformity of the wrist in the resting position was 2 degrees. These variables did deteriorate with time. Extensor carpi radialis longus to extensor carpi ulnaris tendon transfer with crossed intrinsic transfer produced the same result as crossed intrinsic transfer alone. The outcomes for crossed intrinsic transfer attached to the lateral band were similar to outcomes for transfers attached to the collateral ligament of the metacarpophalangeal joint. The crossed intrinsic transfer procedure effectively provides long-term correction of ulnar drift in the rheumatoid hand. PMID- 2584660 TI - Retrograde Herbert screw fixation for treatment of proximal pole scaphoid nonunions. AB - Most nonunions of the carpal scaphoid bone can be treated with a high rate of success by use of conventional bone grafting techniques. However, fractures with a small proximal pole fragment may be difficult to treat by use of these techniques. Nine patients with nonunion and three patients with unstable proximal pole fractures were treated with retrograde dorsal Herbert screw fixation and adjunctive bone grafting. Follow-up averaged 25 months. Of the 12 patients, the fracture healed in 11 and one fracture remained ununited. This technique has been successful in our practice and should be considered in the treatment of small proximal pole nonunions and displaced proximal pole fractures. PMID- 2584661 TI - Hunger pain: a poor indicator of peptic ulcer in a developing country. AB - Endoscopy of the esophagus, stomach, and duodenum and stool examinations for ova and parasites were performed in 63 adult Peruvian patients with "hunger pain" (HP) and other dyspeptic symptoms. No lesion capable of provoking HP was found at endoscopy in 50 (78%) of the 63 patients. Only 7 (12%) of the patients had evidence of active or healed peptic ulcers. Another 6 patients (10%) had either gastric erosions or duodenitis. One (2%) of the patients was infected with hookworm, a parasite that produces epigastric pain mimicking HP. The 12% rate of peptic ulcer in Peruvian patients with HP contrasts strongly with accumulated experience in most developed countries, whose rates of peptic ulcer associated with HP range from 60 to 75%. As the frequency of peptic ulcer is so variable in patients with HP, we suggest that the simple term "hunger pain" be used instead of "peptic ulcer pain" or "ulcer dyspepsia" to refer to the complaint of such patients. PMID- 2584662 TI - Lack of association between gastric emptying of solids and symptoms in nonulcer dyspepsia. AB - Gastric motor dysfunction and concomitant gastric stasis have been implicated in the pathogenesis of nonulcer dyspepsia, but a cause-and-effect relationship is not established. Essential dyspepsia refers to a subgroup of nonulcer dyspepsia patients who have no evidence of irritable bowel syndrome, gastroesophageal reflux, or pancreaticobiliary disease. In 32 patients with essential dyspepsia, and 32 randomly selected dyspepsia-free community controls of similar age and sex, we measured gastric emptying of solids using Tc99m-Sulphur Colloid in a fried egg sandwich. Subjects with neuromuscular or other diseases that may alter gastric emptying were excluded. Symptoms were assessed by a standard questionnaire. Data processing was carried out "blinded" to the subjects' clinical status. Female patients took significantly longer to empty half the initial stomach activity (mean 90 min) than female controls (mean, 73 min; p = 0.02). The rate of emptying at 25 min was also significantly less in female patients than in controls. Female and male controls, and male patients, had similar emptying times. Delayed emptying was not associated with the occurrence of postprandial pain, belching, or nausea; there was a trend for the half-time rate of emptying to be greater in patients with abdominal distention. While gastric emptying of solids is slightly delayed in females with essential dyspepsia as a group, this may not explain their symptoms. PMID- 2584663 TI - Pentagastrin-stimulated gastric acid secretion: does desensitization exist? AB - The existence of tachyphylaxis to pentagastrin-stimulated gastric acid secretion in humans is controversial. To study this, we determined gastric acid output in 19 duodenal ulcer patients following the administration of two successive intramuscular injections of pentagastrin (6 micrograms/kg body weight). In 18 of 19 patients, the maximal acid output decreased by 33.73 +/- 3.25% (mean +/- SE) following the second pentagastrin administration when compared with the maximal acid output following the first injection. This study indicates the existence of tolerance to pentagastrin-induced gastric acid secretion in humans, which may be due to a receptor-mediated phenomenon of "down-regulation." PMID- 2584664 TI - The effect of simethicone on colonic visibility after night-prior colonic lavage. A double-blind randomized study. AB - We prospectively studied 26 patients receiving simethicone (n = 14) or placebo (n = 12) in Colyte (Edlaw Preparations. Inc., Farmingdale, NY, U.S.A.) to determine if the addition of simethicone could improve visibility when administered the night before colonoscopy. Two parameters of visibility were assessed: amount of bubbles and degree of haziness. The effectiveness of a night-prior administration of Colyte to clean the colon of feculent debris was also examined. Patients receiving simethicone had significantly less bubbles (p less than 0.02), but haziness was not improved (p = 0.9). The presence of feculent debris that interfered with the colonoscopic examination was similar in both groups: simethicone 5 of 14 or 35% and placebo 7 of 12 or 58%. Eighty percent (four of five) of patients with feculent debris in the rectosigmoid colon had diverticulosis, and 50% (four of eight) patients with diverticulosis had feculent debris in the rectosigmoid. These data indicate that (a) the combination of simethicone plus Colyte administered the night before colonoscopy improves visibility by diminishing bubbles; (b) this dosage of simethicone is not effective in diminishing haziness when administered the night before colonoscopy; and (c) patients with diverticulosis are likely to have feculent debris in the rectosigmoid colon, and a precolonoscopy enema may be helpful when the diagnosis is known. PMID- 2584665 TI - Hepatic sinusoidal dilatation in rheumatoid arthritis. AB - In a review of 100 consecutive patients with adult rheumatoid arthritis (RA), clinical evidence of liver disease was absent, whereas minor abnormalities of liver biochemistry, mainly a raised alkaline phosphatase, were present in 32 cases. Liver biopsies were obtained in eight patients; the most striking finding was the presence of sinusoidal dilation in all samples, with a normal central vein and preservation of hepatic architecture. The mechanism of this nonspecific histological change is not known, though it could be speculated to be secondary to a humoral factor related to RA. We conclude that hepatic involvement in adult RA is common but trivial and that routine liver biopsy is not indicated. PMID- 2584667 TI - Esophageal perforation at a Barrett's ulcer. AB - An alcoholic man with known reflux esophagitis and Barrett's esophagus developed fever, epigastric pain, subcutaneous crepitus, and leukocytosis from an esophageal perforation at a Barrett's ulcer. Possible risk factors for perforation in this patient included alcoholism, severe gastroesophageal reflux, corticosteroid therapy, noncompliance with antacid and H2 blocker therapy, and the presence of acid-secreting parietal cells in the Barrett's epithelium. Five cases of this complication have previously been reported in a review of the literature, which included 536 cases of Barrett's esophagus or esophageal perforation. This entity may present with a clinical triad of a patient (a) in acute distress with fever and epigastric or noncardiac chest pain and without signs of peritonitis, (b) with symptoms of or known gastroesophageal reflux, and (c) with chest examination revealing subcutaneous crepitus, or chest roentgenogram revealing subcutaneous emphysema, pneumomediastinum, or hydropneumothorax. PMID- 2584666 TI - Results of distal splenorenal shunt with versus without splenopancreatic disconnection. AB - From December 1973 to December 1987, we performed a distal splenorenal shunt (DSRS) in 112 cases of portal hypertension, including 107 with postnecrotic liver cirrhosis and 5 with idiopathic portal hypertension (IPH). They comprised about 50% of our surgical cases with esophageal varices. In 1981, we modified our operative procedure towards a more extended splenopancreatic disconnection (SPD) in order to prevent the "stealing" of the shunt through the pancreatic vein. In one group of 69 patients who underwent DSRS alone, the operative mortality was 2.9%; postoperative encephalopathy was seen in 17.4%, late hepatic failure in 40.6%, and recurrence of varices in 4.3%. In the other group, 43 patients who underwent DSRS with SPD, there were no operative deaths, no encephalopathy (better than DSRS alone at p less than 0.05), and late hepatic failure was seen in only 9.3% (better than DSRS alone at p less than 0.025), while the recurrence rate of 7% was the only statistical increase. These data show that DSRS + SPD can improve chances of survival. PMID- 2584668 TI - Multinodular adult hypertrophic pyloric stenosis. AB - A case of multinodular hypertrophic pyloric stenosis is described in a 57-year old woman. Over a 3-month interval, there was progressive enlargement of several mucosal nodules overlying hypertrophied muscularis, and one nodule obstructed the pyloric opening. Diagnosis was made at operation and symptoms resolved after Billroth I gastrectomy. PMID- 2584669 TI - The prolonged course of gastrointestinal tuberculosis. AB - Review of biopsy specimens showed that a patient incorrectly diagnosed 7 years ago as having Crohn's disease actually had histologically proven gastrointestinal tuberculosis of 7 years' duration. It is significant that gastrointestinal tuberculosis and Crohn's disease can mimic each other not only in their clinical, radiologic, and histologic manifestations but also temporally. We discuss the interrelationship between AIDS, tuberculosis, and inflammatory bowel disease. PMID- 2584670 TI - Rapid development of pancreatitis following reuse of 6-mercaptopurine. AB - A patient with Crohn's disease developed acute pancreatitis 4 h after retaking one 50 mg dose of orally administered 6-mercaptopurine (6-MP). All seven previously reported patients who were rechallenged with 50 mg or more of 6-MP developed pancreatitis within 48 h. These findings suggest that 6-MP can produce pancreatitis due to an idiosyncratic immune-mediated response. Patients with this complication should not reuse 6-MP. PMID- 2584671 TI - Distal colonic impaction requiring laparotomy in an adult with cystic fibrosis. AB - A sigmoid fecal impaction leading to colonic obstruction in an adult with cystic fibrosis was evacuated at laparotomy by manual compression of the inspissated stool through the rectum. In cystic fibrosis beyond infancy, constipation is a common management problem. Intestinal obstruction caused by inspissated stool in the terminal ileum and cecum has been well documented; however, distal colonic obstruction requiring operation has not been previously reported. PMID- 2584672 TI - Toxic epidermal necrolysis associated with acute cholestatic viral hepatitis A. AB - A 35-year-old man with obvious hepatitis A (HA) developed toxic epidermal necrolysis, which, we suggest, may have been a direct result of the infection with HA virus. PMID- 2584673 TI - Primary biliary cirrhosis: management of an unusual case with severe xanthomata by hepatic transplantation. AB - We report a patient with advanced primary biliary cirrhosis associated with Sjogren's syndrome, xanthelasma, and extensive, painful xanthomata involving cutaneous lipid deposits on her face, abdomen, hands, and buttocks and extensor surfaces over many joints. Despite conventional dietary and drug therapy, these lesions progressed rapidly over 3 years. There was symptomatic improvement of the xanthomata, but no objective amelioration of the xanthomatosis with the use of plasmapheresis over an 18-month period. Liver transplantation was undertaken for decompensated chronic liver disease and poor quality of life due to complications of xanthomatosis. Twelve months after transplantation, all xanthomata and xanthelasma and symptoms attributable to xanthomata had disappeared. Liver transplantation is a drastic but successful remedy for complications of abnormal lipid metabolism associated with primary biliary cirrhosis. PMID- 2584674 TI - Ulcerative colitis and Crohn's disease--one or two diseases? PMID- 2584675 TI - Questions raised about June issue. PMID- 2584676 TI - Cross-sectional survey sampling. PMID- 2584677 TI - HIV transmission, healthcare workers and media hype. PMID- 2584678 TI - The high rate of blood donor exposure for critically ill neonates. AB - The purpose of this study was to determine the number and volume of red blood cell (RBC) transfusions and the number of donors a newborn is exposed to during his or her newborn intensive care unit (NICU) stay. On one day at the Medical University of South Carolina (MUSC) and two days at the University of Virginia Hospital (UVH) all babies who had or were receiving RBCs comprised the study group. Patient records were reviewed at discharge. Fifty-two (70%) of the 75 NICU babies had or were receiving RBCs and were enrolled. The average number of RBC transfusions was nine (range 1 to 28, median 7) and the average transfusion volume was 16.5 ml (range 5 to 60) for a total volume of 148 ml transfused during a NICU stay. Each baby was exposed to an average of 6.9 donors (range 1 to 25, median 6.5). The practice of splitting RBC packs to share among different infants and of giving multiple small volume transfusions maximizes donor exposure and transfusion-related infectious risks in this population. PMID- 2584679 TI - Pseudoepidemic of Rhodotorula rubra in patients undergoing fiberoptic bronchoscopy. AB - Between March and June 1988, Rhodotorula rubra was isolated from the bronchial washings of 30 of 56 (54%) patients undergoing bronchoscopy at a North Carolina community hospital. Pulmonary disease consistent with invasive fungal pneumonia was not apparent for any patient. Repeat sputum cultures were performed on 11 patients, none of whom were positive for R rubra. Investigation revealed fungal contamination of two brushes used to clean the bronchoscope channels and one positive sample of the tub water used to test the integrity of the bronchoscope prior to cleaning and disinfection. Control measures instituted were high-level disinfection of all equipment used to clean the bronchoscopes, including the brushes, complete air drying of the bronchoscopes before storing and storage of equipment in closed cabinets. An additional case one month after instituting these measures prompted the addition of a final 70% ethyl alcohol rinse of the bronchoscopes immediately prior to storage. Over a six-month period no additional cases have been identified. Despite published disinfection guidelines, pseudoepidemics and infections from contaminated equipment continue to appear. This pseudoepidemic investigation revealed a site for contaminating bronchoscopes that has not been previously reported, the inner cannula cleaning brushes. This emphasizes the need for stringent adherence to recommended cleaning and disinfection guidelines. PMID- 2584680 TI - Evaluation of rigid container systems for sterilization. PMID- 2584681 TI - Nurse's accounts of nursing the terminally ill on a coronary care unit. AB - This paper is based on nurses' reported experiences about nursing people dying in a coronary care unit, and their attitudes towards such work. Two patterns of dying associated with cardiac arrest and cardiac failure were typical in the unit, each with its difficulties and problems. However, the nurses did not report any severe coping difficulties associated with their nursing care of dying patients. Their most severe difficulties were those relating to telling relatives about a patient's death. Elements within the unit's ethos and organisation associated with this positive coping were the high staff-patient ratio, low staff turnover, good and supportive relationships among staff, and the policy of open and honest communication about prognosis. Of particular importance was the feeling that everything that it was possible to have done for the patient had been done. PMID- 2584682 TI - Kegworth: an ICU experience. PMID- 2584684 TI - The Indiana Poison Center: a valuable resource for Indiana physicians. PMID- 2584683 TI - Coping with disaster--and afterwards. PMID- 2584685 TI - Abnormal bones in a 25-year-old man. PMID- 2584686 TI - Monoclonal antibodies: a short history. PMID- 2584687 TI - Infertility as a crisis experience. PMID- 2584688 TI - Managing HIV-seropositive adults without AIDS. PMID- 2584689 TI - PREVENTION: ten ways to diminish malpractice losses. PMID- 2584690 TI - Digest of Health and Medical Laws. 1989 Indiana General Assembly. PMID- 2584691 TI - Nursing's image in Indiana. PMID- 2584692 TI - Distribution of protein disulfide isomerase in rat epiphyseal chondrocytes. AB - We investigated the intracellular distribution of protein disulfide isomerase (PDI) in rat epiphyseal chondrocytes by immunocytochemistry, using a post embedding protein A-gold technique. Gold particles were localized primarily in the cisternal space of the rough endoplasmic reticulum (ER) and nuclear envelopes. The ER cisternae of the chondrocytes in all the differentiating epiphyseal zones--resting, proliferative, pre-hypertrophic, and hypertrophic- were equally and highly labeled. The labeling density of the cisternal space of the dilated ER, probably reflecting marked accumulation of secretory proteins such as procollagen, was always higher than that of the non-dilated ER. In the dilated cisternal space, gold particles were freely and evenly distributed, without preferential binding to the luminal surface of the ER membranes. We suggest that PDI catalyzes the formation of disulfide bonds of various secretory proteins, perhaps type II procollagen, in the cisternal space of the ER in epiphyseal chondrocytes. The exclusive localization of gold particles in the cisternal space of the ER and nuclear envelopes and the lack of gold particles in the Golgi apparatus, including cis-Golgi cisternae, indicate that PDI is an ER soluble protein in the chondrocytes and is presumably sorted out in some pre Golgi compartment and not transported to the Golgi apparatus. PMID- 2584693 TI - An immunogold-silver staining method for detection of cell surface antigens in cell smears. AB - We developed an indirect immunogold-silver staining method for detection of leukocyte cell surface antigens in cell smears. Air-dried and fixed cytocentrifuge preparations or smears of peripheral blood leukocytes were incubated with monoclonal antibodies (MAb) and colloidal gold-labeled secondary antibodies. The preparations were post-fixed and silver enhancement was performed. The smears were counterstained with May-Grunwald-Giemsa and examined in brightfield light microscopy. The morphology of the cells was well preserved. Leukocytes reacting with the MAb showed black granules on their surface membranes. The intense immunostaining and the low background allowed a rapid enumeration of the positive cells. The labeling could be detected with high sensitivity by epipolarization microscopy. This immunogold-silver staining method was used to quantify T- and B-lymphocytes and natural killer cells in buffy coat smears of normal adult blood. These lymphocyte subsets correlated well with those obtained in smears with the alkaline phosphatase-anti-alkaline phosphatase (APAAP) method and with those found by labeling of mononuclear cells in suspension with immunogold-silver staining. This immunogold-silver staining method forms a good alternative to immunoenzyme methods for study of hematologic cells. In addition, it could be a general procedure for detection of cell surface antigens in all kinds of cell smears. PMID- 2584694 TI - The known purified mammalian 2,4-dienoyl-CoA reductases are mitochondrial isoenzymes. AB - The aim of this work was to determine the subcellular location of mammalian 2,4 dienoyl-CoA reductase, a key enzyme for degradation of polyunsaturated fatty acids by beta-oxidation. The enzyme was purified according to Kimura et al. (J Biochem 96:1463, 1984), and antibodies were raised in rabbits. Monospecific antibodies were obtained via purification on an affinity column. Immunoblotting of isolated rat liver mitochondria and peroxisomes with the monospecific reductase antibody showed that the antigen was located only in mitochondria. Immunocytochemical experiments with liver tissue, using the protein A-gold labeling technique, confirmed this result. The similarity of their characteristics suggests that the purified reductases described in the literature are the same isoenzyme. Consequently, since the rat enzyme was localized here to the mitochondria, purification and characterization of peroxisomal mammalian reductases remain to be achieved in the future. In addition, a significant induction also of mitochondrial reductase by clofibrate was observed in the immunoblotting experiments. PMID- 2584695 TI - Histochemical identification of the vascular endothelial isoenzyme of alkaline phosphatase. AB - Alkaline phosphatase (AP) is a widely studied membrane bound ecto-enzyme with an extensive distribution in nature. Three major human isoenzymes have been defined and can be distinguished on the basis of their differential sensitivity to specific inhibitors. Despite the voluminous literature describing AP, the physiological role of this enzyme is unclear. Microvascular endothelium is strongly AP positive and may provide a convenient model for study of the role of AP in vitro. This report describes the use of freeze-substitution and high resolution plastic embedding techniques to identify the isoenzyme of endothelial AP by quantitative analysis of the relative inhibition by specific inhibitors of AP, using human gingival tissues and a number of rat tissues. Endothelial AP is found to be the liver/bone/kidney isoenzyme, indicating kidney as a credible source of enzyme for further experimental work investigating the role of AP. PMID- 2584696 TI - Autonomic control of the diurnal variation in arterial blood pressure and heart rate in spontaneously hypertensive and Wistar-Kyoto rats. AB - The relative influences of sympathetic and parasympathetic neural modulation on mean arterial pressure (MAP) and heart rate (HR), and their respective variabilities, were studied in young spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). An on-line computerized system was used for continuous intra-arterial measurements of MAP and HR in unrestrained rats. In addition, the autonomic nervous control of MAP and HR was studied in ageing SHR and WKY. Both WKY and SHR showed diurnal rhythms with regard to MAP and HR. The MAP variability was higher in SHR than in WKY during both daytime (inactive) and night-time (active), and did not change in response to either beta 1-adrenoceptor- or cholinergic blockade. Structural vascular changes, with a resultant increase in reactivity, may explain the elevated MAP variability in SHR. HR variability was clearly reduced in SHR; this was not influenced by vagal blockade, whereas HR variability was significantly reduced in WKY. This pattern is suggested to be due to a reduced tonic vagal discharge in SHR, as part of a persistent, mild defence reaction. The initial reduction in vagal activity will in turn eliminate vagally mediated tachycardias. Furthermore, administration beta 1-blockade to SHR of different ages caused a greater fall in MAP and HR than in WKY, indicating an increased dependence upon the sympathetic nervous system in SHR with age. PMID- 2584697 TI - DNA fingerprinting of spontaneously hypertensive and Wistar-Kyoto rats: implications for hypertension research. AB - Probes to hypervariable minisatellite regions of DNA identify multiple loci scattered over the autosomal chromosomes and produce a complex Southern blot pattern of fragments termed a DNA 'fingerprint'. As concern has been raised that different stocks of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) may not be biologically identical, we have compared the DNA of SHR and WKY from several sources using two such probes which identify different sets of minisatellite sequences. While the DNA fingerprints of SHR from the various sources were identical, variability was observed in those of WKY, indicating genetic heterogeneity between different WKY stocks. In animals from one of the commercial suppliers even inter-rat variability in DNA fingerprints was seen, suggesting genetic heterogeneity within that single colony. These observations indicate that experimental results obtained using WKY from different sources may not be directly comparable and could provide an explanation for some of the conflicting data that exist on the comparative characteristics of SHR and WKY. In separate studies, direct comparisons both of the DNA fingerprints of SHR and WKY and of SHR and stroke-prone spontaneously hypertensive rats (SHRSP) showed multiple differences between the strains. The polymorphisms seen could provide useful linkage markers in locating the chromosomal sites of the genetic loci responsible for raised blood pressure in the SHR and the propensity to strokes in the SHRSP. PMID- 2584698 TI - The development of hypertension care in Finland from 1982 to 1987. AB - The development of hypertension care in Finland was evaluated using the data from two independent population samples of the FINMONICA Project comprising 9350 and 6250 persons examined in 1982 and 1987, respectively. The sampling frame was the population aged 25 to 64 years in the provinces of North Karelia and Kuopio in eastern Finland and in the Turku-Loimaa region in south-western Finland. During the 5-year period, the mean systolic blood pressure levels decreased in all of the groups except the North Karelian men. Mean diastolic blood pressure did not change significantly. The proportion of hypertensive men with adequately controlled blood pressure increased from 22.6 to 29.4% [difference 6.8%, 95% confidence interval (Cl) for the difference 2.4-11.2] during 1982-1987. At the same time, the proportion of hypertensive men unaware of their condition fell from 30 to 20.9% (difference -9.1%, 95% Cl for the difference -13.4- -4.8). There was corresponding falls for women from 39.2 to 41.3% (difference 2.1%, 95% Cl for the difference -3.1-7.3) and from 15.4 to 13.1% (difference -2.3%, 95% Cl for the difference 1.4- -6.0), respectively. Thus, obvious progress had taken place, although the situation remained far from satisfactory. The possibility of overly aggressive treatment of hypertension was also investigated. It was found that only less than 10% of the middle-aged hypertensive men treated with drugs had diastolic pressures less than or equal to 85 mmHg, suggesting that this might not be an issue of concern at community level. PMID- 2584699 TI - Blood pressure measurement in children: the importance of cuff bladder size. AB - The effect of cuff bladder size on blood pressure measurement has been investigated in 838 children aged 5-7 years, using a Dinamap oscillometric automated blood pressure recorder and a Hawksley random zero sphygmomanometer. With both instruments the smallest (infant) cuffs recorded higher pressures than the child cuffs (mean systolic differences: Dinamap 4.6 mmHg, Hawksley 6.6 mmHg), which in turn recorded higher pressures than the largest (adult) cuffs (mean systolic differences: Dinamap 5.5 mmHg, Hawksley 8.1 mmHg). These differences in measurement between cuffs are sufficiently large as to be of concern in both clinical and epidemiological studies. Since they are little affected by arm circumference, their occurrence cannot be prevented simply by following current guidelines for selection of cuff size. Methods of dealing with these problems are discussed. PMID- 2584700 TI - Perforin mRNA in primary peritoneal exudate cytotoxic T lymphocytes. AB - Considerable evidence indicates that cloned CTL cell lines kill target cells by releasing toxic granules that contain a cytolytic protein, called perforin, and several serine esterases (granzymes A to F). However, primary CTL, such as the highly cytolytic peritoneal exudate lymphocyte (PEL) cell population, have been found by a hemolytic assay to have no perforin, or perhaps only borderline levels of that protein, suggesting that these cells use a different lytic mechanism. To determine whether or not primary CTL express the perforin gene, we have here compared mRNA from PEL CTL and from a cloned CTL cell line, 2C, by Northern blot analysis using a perforin cDNA probe. CD8+ PEL CTL contain approximately 30% of the amount of perforin message present in 2C. Moreover, depletion of CD8+ T cells from the total peritoneal exudate cell population removes both cytolytic activity and perforin message. We have previously shown that PEL CTL elicit the same changes in target cells as cloned CTL cell lines and are resistant to lysis by the toxic granules purified from these cells lines. Taken together these results are consistent with the view that primary CTL, as well as long term cloned CTL cell lines, exercise their cytolytic activity by means of perforin. PMID- 2584701 TI - Location of hemopoietic stem cells influences frequency of lymphoid engraftment in Xenopus embryos. AB - The first hemopoietic stem cells to differentiate in Xenopus embryos arise from ventral blood island (VBI) mesoderm. Progeny of these stem cells contribute to larval E, macrophage, thymocyte, and B lymphocyte populations. When small pieces of mesoderm are transplanted to a central location within the VBI, the contribution of this mesoderm is predominantly to erythropoiesis and engraftment of lymphoid populations is minimal. The present experiments examined the influence of position within the VBI on the contribution of single stem cells to lymphoid populations. Pieces of diploid VBI mesoderm, containing an average of one hemopoietic stem cell, were transplanted to either a central or a peripheral location within the defined boundaries of the VBI of triploid, stage matched embryos. The number of animals with donor-derived cells in lymphoid populations was markedly increased when stem cells were grafted to a peripheral position. In three cases, stem cells contributed to lymphoid populations at the exclusion of erythroid populations. These data were consistent with the notion of either a lymphoid stem cell or restricted B and T lymphocyte precursors. These data also suggested that during embryogenesis, stochastic differentiation of hemopoietic stem cells was influenced by regional differences in the VBI microenvironment. PMID- 2584702 TI - Tumor necrosis factor and IL-1 in New Zealand Black/White mice. Enhanced gene expression and acceleration of renal injury. AB - TNF and IL-1 are potent immunologic and inflammatory cytokines. We have previously reported increased levels of mRNA for TNF alpha and IL-1 beta in MRL lpr mice with lupus nephritis. To determine whether the increased levels of TNF and IL-1 mRNA are a more general feature of mice with lupus nephritis we studied cytokine gene expression in female NZB x NZW F1 (NZB/W) mice by Northern blot analysis. Enhanced steady state levels of mRNA for TNF alpha and IL-1 beta, but not IL-1 alpha, were detected in the renal cortices of animals with lupus nephritis. To determine whether administration of TNF or IL-1 would accelerate renal injury and mortality, we injected murine rTNF alpha or rIL-1 alpha i.p. into female NZB/W or C3H/FeJ mice at two doses, 2.0 micrograms or 0.2 micrograms, three times weekly for 2 or 4 mo beginning at 2 or 4 mo of age. Administration of the lower dose of each cytokine accelerated renal disease and mortality rate when treatment was initiated at 4 mo of age. At the higher dose, neither cytokine promoted disease. Treatment administered from 2-4 mo of age did not accelerate renal disease. This observation suggests that in order to cause renal injury, these cytokines must interact with other pathologic features present in these animals after 4 mo of age. These findings support the hypothesis that TNF and IL 1 can contribute to nephritis in murine models of lupus. Taken together with previously published data, we propose that TNF and IL-1 have differential dose effects on renal disease. The dose of TNF and IL-1 and the stage of disease activity dictate the pathogenic action of these cytokines. PMID- 2584703 TI - Effects of T cell depletion in radiation bone marrow chimeras. III. Characterization of allogeneic bone marrow cell populations that increase allogeneic chimerism independently of graft-vs-host disease in mixed marrow recipients. AB - The opposing problems of graft-vs-host disease vs failure of alloengraftment severely limit the success of allogeneic bone marrow transplantation as a therapeutic modality. We have recently used a murine bone marrow transplantation model involving reconstitution of lethally irradiated mice with mixtures of allogeneic and syngeneic marrow to demonstrate that an allogeneic bone marrow subpopulation, removed by T cell depletion with rabbit anti-mouse brain serum and complement (RAMB/C), is capable of increasing levels of allogeneic chimerism. This effect was observed in an F1 into parent genetic combination lacking the potential for graft-vs-host disease, and radiation protection studies suggested that it was not due to depletion of stem cells by RAMB/C. We have now attempted to characterize the cell population responsible for increasing allogeneic chimerism in this model. The results indicate that neither mature T cells nor NK cells are responsible for this activity. However, an assay involving mixed marrow reconstitution in an Ly-5 congenic strain combination was found to be more sensitive to small degrees of stem cell depletion than radiation protection assays using three-fold titrations of bone marrow cells. Using this assay, we were able to detect some degree of stem cell depletion by treatment with RAMB/C, but not with anti-T cell mAb. Nevertheless, if the effects of alloresistance observed in this model are considered, the degree of stem cell depletion detected by such mixing studies in insufficient to account for the effects of RAMB/C depletion on levels of allogeneic chimerism, suggesting that another cell population with this property remains to be identified. PMID- 2584704 TI - IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice. AB - Incubation of the human U937 histiocytic lymphoma cell line with granulocyte macrophage colony stimulating factor (GM-CSF) rendered the cells responsive to induction of TNF by LPS. Treatment with IL-6 reduced TNF production in GM-CSF primed U937 cells. The inhibitory effect was most pronounced (approximately equal to 80%) when IL-6 was added either along with GM-CSF or within the first 3 h of GM-CSF treatment. Both GM-CSF or IL-6 inhibited [3H]TdR uptake in U937 cells, and simultaneous treatment with GM-CSF and IL-6 resulted in an additive inhibitory effect on cell proliferation. However, the inhibition of TNF production could not be explained by the inhibitory effect of IL-6 on cell growth, nor was it due to a reduction in cell viability. An inhibition of TNF production by IL-6 was also demonstrated in cultured human peripheral blood monocytes. Treatment with IL-6 also resulted in a dose-dependent reduction of the 17-kDa TNF band revealed by SDS-PAGE after labeling monocytes with [35S]cysteine and immunoprecipitation with anti-TNF mAb. In addition, treatment with IL-6 resulted in a reduction of monocyte in vitro cytotoxicity for tumor target cells. Finally, in mice sensitized by the administration of Bacillus Calmette-Guerin, the injection of IL 6 significantly reduced the levels of TNF found in the serum upon challenge with LPS. Inasmuch as TNF is known to be an inducer of IL-6, the inhibitory action of IL-6 on TNF production may represent the negative arm of a regulatory circuit. The inhibitory action of IL-6 on TNF production is consistent with a predominantly antiinflammatory role of IL-6 in the intact organism. PMID- 2584705 TI - IL-2 induction of IL-1 beta mRNA expression in monocytes. Regulation by agents that block second messenger pathways. AB - We have previously shown that in mixed cultures of PBL incubation with human rIL 2 induces the rapid expression of IL-1 alpha and IL-1 beta mRNA. Because studies have demonstrated that IL-2R can be expressed on the surface of human peripheral blood monocytes, we chose to investigate whether IL-1 beta mRNA could be directly induced in purified human monocytes by treatment with Il-2 and, if so, to analyze the second messenger pathways by which it may be controlled. Human monocytes do not spontaneously express IL-1 beta mRNA, but can express the gene as soon as 1 h after treatment with IL-2. The level of IL-1 beta mRNA induced by IL-2 at 5 h in human monocytes was about one-fourth that induced by LPS. LPS induction of IL-1 beta mRNA in human monocytes can be blocked by either an inhibitor of protein kinase C (PKc) 1-(5-isoquinolinesulfonyl)-2-methylpiperazine or an inhibitor of calcium/calmodulin (CaM) kinase N-(6-aminohexyl) 5-chloro-1 naphthalenesulfonamide, suggesting that both PKc and CaM kinase are involved in transducing signals initiated by LPS. In contrast, IL-2 induction of IL-1 beta mRNA expression is blocked only by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, suggesting that PKc, and not CaM kinase, is activated by IL-2. These data suggest that overlapping but distinct second messenger pathways are involved in the transduction of signals initiated by IL-2 and LPS. PMID- 2584706 TI - Contribution of IL-6 to the antiproliferative effect of IL-1 and tumor necrosis factor on tumor cell lines. AB - The role of IL-6 in the antiproliferative effect of IL-1 for tumor cell lines was investigated using IL-1-sensitive cell lines. Human recombinant IL-1 alpha and IL 6 both inhibited the growth of an IL-1-sensitive cloned human melanoma cell line (A375-C6). However, IL-1 has greater maximum growth inhibitory activity than IL 6. Conditioned medium of the tumor cells that were treated with IL-1 contained IL 6 as determined by ELISA. Northern blot analysis revealed that IL-6 mRNA expression increased in IL-1-treated cells. In addition, antibody against human IL-6 neutralized about 50% of the antiproliferative effect of IL-1. The growth of an IL-1-resistant clone of A375 cells (A375-C5), which cannot be shown to express any detectable IL-1R, was inhibited by IL-6 to the same degree as A375-C6 cells. The A375-C5 cell line did not produce IL-6 or increase IL-6 mRNA after stimulation with IL-1. These results indicate that IL-6 mediates in part the antiproliferative effect of IL-1 on A375-C6 cells by acting as an autocrine antiproliferative factor. IL-1 also inhibited the growth of a malignant human mammary cell line (MDA-MB-415). IL-6 exhibited only slight growth inhibition in this cell line. Neither IL-6 production nor IL-6 mRNA expression was induced in this cell line by IL-1. Antibody against IL-6 did not neutralize the antiproliferative effect of IL-1. Therefore, for MDA-MB-415 cells IL-6 appeared not to be involved in the antiproliferative effect of IL-1. These results indicate that the antiproliferative effect of IL-1 involves at least two pathways, one IL-6 dependent and another IL-6 independent. The contribution of IL 6 to the antiproliferative effect of TNF was also examined. IL-6 appeared not to play a role in the antiproliferative effect of TNF in these cell lines. PMID- 2584707 TI - Differential expression of the IL-2 receptor subunits, p55 and p75 on various populations of primary peripheral blood mononuclear cells. AB - Unstimulated PBL were examined for expression of IL-2R subunits, IL-2Rp55 and IL 2Rp75, by two-color flow cytometric analyses using mAb. NKH-1+ non-T non-B cells expressed IL-2Rp75 but not IL-2Rp55, and the IL-2Rp75 sites on purified NKH-1+ cells were determined to be 1630 sites/cell by binding of 125I-labeled TU27 mAb specific for IL-2Rp75. In the CD4+ T cell population, IL-2Rp55+ cells were significantly detected, but little or marginally of the IL-2Rp75+ cells. However, IL-2Rp75+ cells were significantly detected, but little of the IL-2Rp55+ cells in the CD8+ T cell population. The IL-2Rp75 sites on CD8+ T cells were estimated at approximate 180-410 sites/cell. In the CD4+ T cells, expression of IL-2Rp75 as well as IL-2Rp55 was induced by stimulation with PHA. IL-2Rp75+ cells, but not IL 2Rp55+ cells, were also detected in the CD14+ monocyte population. In the CD20+ B cell population, a small number of IL-2Rp55+ cells was detected, but little of the IL-2Rp75+ cells. PMID- 2584708 TI - The main immunogenic region of the nicotinic acetylcholine receptor. Identification of amino acid residues interacting with different antibodies. AB - In myasthenia gravis a highly conserved area of the nicotinic receptor (AcChR) dominates the autoantibody response (main immunogenic region, MIR), and it is formed by residues within the sequence segment 67-76 of the AcChR alpha-subunit. We have studied the binding of eight anti-MIR mAb to synthetic peptides containing the sequence segment 67-76 of the human alpha-subunit, and peptide analogues containing single residue substitutions of this sequence. We used also a peptide where both Asp70 and Asp71 were substituted by glycine residues. The binding of six anti-MIR mAb was strongly influenced by several substitutions. All these mAb required residues Asn68, and Pro69 for binding. Five of them required also Asp71 and Tyr72. Substitution of Asp70, which is an Ala residue in Torpedo AcChR, was irrelevant for the binding of an anti-Torpedo and an anti Electrophorus mAb, and moderately reduced the binding of an anti-human mAb (no. 203). Substitution of Trp67 moderately reduced the binding of some of these mAbs. A mAb of this group (the antihuman mAb no. 198) bound in a manner only slightly influenced by ionic strength, whereas the binding of the other five mAb of this group was very sensitive to the ionic strength. Two anti-Electrophorus MIR mAb bound similarly to all peptide analogues in low ionic strength. At high ionic strength only the peptide analogue where Asp 70 was changed to a Gly residue bound significantly. This may indicate that the Electrophorus MIR has an uncharged residue at this position, as does Torpedo AcChR. Residues at position 73, 74, 75, and 76 were of little or no importance for the binding of all anti MIR mAb. A free amino terminus was essential for the binding of most mAb. The results of competition experiments between different peptides and native AcChR for mAb binding were consistent with those obtained in direct binding experiments. PMID- 2584709 TI - Immunochemistry of the dominating antigenic region Ala582 to Cys604 in the transmembranous protein of simian and human immunodeficiency virus. AB - The immunochemistry of two homologous uniquely antigenic peptides representing Ala582 to Cys604 in the transmembrane proteins of simian immunodeficiency virus of rhesus macaque origin, SIVmac (closely related to HIV-2) and HIV-1 (strain HTLV-IIIB) was characterized at the resolution of single amino acids. Five different antigenic sites were identified in the SIVmac peptide by use of 34 mAb against this peptide and two different sites were similarly demonstrated in the HIV-1 peptide by use of 10 peptide-specific mAb. Within some sites the mAb could be subgrouped to show a progressively more narrow epitopic dependence on amino acids in the central part of the site. Three SIVmac peptide mAbs had a remarkably narrow amino acid dependence, Glu584 and Tyr586. Anti-peptide mAbs reacting with the site Trp596 to Gln602 effectively blocked the capacity of the peptide to react with human postinfection HIV-2 antibodies previously demonstrated to have a restricted reactivity involving this site. No similar blocking was seen when mAb specific for Leu587 to Gln590 were used except with a single broadly reacting HIV 2 serum, which depended on an amino acid at a distance of only 6 residues, Trp596. A cross-reacting site involving amino acids Ala582 to Glu588/Lys588 was identified with mAb and rabbit hyperimmune sera against the two peptides. This site was not accessible in the intact transmembrane proteins as determined by ELISA and Western blot tests. Antipeptide mAb against other sites as well as rabbit sera reacted strongly in these tests and can be used as type-specific, component-unique reagents. PMID- 2584710 TI - The role of the Ia-invariant chain complex in the posttranslational processing and transport of Ia and invariant chain glycoproteins. AB - The invariant chain (Ii) is a nonpolymorphic glycoprotein that associates with the Ia alpha- and beta-chains of MHC class II Ag during their transport to the cell surface. Although surface expression of Ia can occur in the absence of Ii, it has not been shown whether the intracellular association of Ia and Ii affects the biosynthetic rate or specificity of posttranslational modifications to the individual molecules. Analysis of transfected cell lines carrying either Ia, Ii, or both Ia and Ii demonstrated efficient assembly of alpha-beta whether or not Ii was present. Pulse-chase studies and two-dimensional gel electrophoresis showed that Ii did not affect the addition of Ia N-linked oligosaccharide chains, or the extent or rate of their conversion to the complex form, nor did it affect the sulfation of alpha and beta glycoproteins. Ii also did not affect the rate of Ia synthesis or appearance of Ia at the cell surface. In contrast, Ia dramatically affected the posttranslational modification of Ii. Although invariant chain was modified by addition of fatty acid, N-linked oligosaccharide, and glycosaminoglycan in the absence of Ia, the processing of Ii-linked oligosaccharide into more acidic, terminally glycosylated forms was significantly less when Ia was absent, and although conversion to proteoglycan did occur, the glycosaminoglycan chains were significantly shorter than normal. The disappearance of radiolabel from the 31,000 Da form of Ii was faster when Ia was present, and the processing of Ii was more rapid when it was associated with Ia. Thus, the rate and manner in which Ii enters and passes through the Golgi is critically affected by Ia. PMID- 2584711 TI - Quantitative analyses of C3b capture and immune adherence of IgM antibody/dsDNA immune complexes. AB - We isolated the IgM fraction from the plasma of an SLE patient with high titer anti-dsDNA antibodies and prepared soluble IgM/dsDNA immune complexes (IC) that fixed C and captured sufficient C3b to bind to human E via their C3b/C4b receptor, CR1 (immune adherence, IA). We used specific 125I-labeled mAb to IgM, C3b, and IgG to measure the stoichiometries of these C-opsonized IC. They contained 10 to 60 C3b and 10 to 30 IgM per PM2 dsDNA, had no detectable IgG, and the vast majority of the C3b was bound to the IgM, and not to the dsDNA. These stoichiometries are in contrast to those we observed for comparable E-bound IC prepared with IgG anti-dsDNA antibodies (100 to 200 C3b, and 200 to 500 IgG). Our results help explain the greater lability of the IgM IC with respect to IA as evidenced by their plasma-mediated release from human E (presumably due to factor I), and confirm previous predictions of a lower density of "packing" of IgM on dsDNA, compared to IgG. The detailed stoichiometry of C3b capture by the IgM IC (typically 1.5 to 3 C3b per IgM) suggests that individual IgM molecules with multiple C3b facilitate IC binding to clusters of CR1. Finally, comparison of the IgM/dsDNA IC with other IgM IC which have been investigated with respect to C activation, and review of the proposed mechanism by which IgM activates C, suggests that the nature of the Ag plays a fundamental role in determining whether or not an IgM IC can activate C and participate in IA. PMID- 2584712 TI - Regulation of macrophage physiology by L-arginine: role of the oxidative L arginine deiminase pathway. AB - The L-arginine content of the extracellular fluid in sites of predominant macrophage infiltration is reduced below plasma levels due to the activity of macrophage-derived arginase. Investigation of the effects of altered L-arginine availability on macrophage physiology reveals that culture of rat peritoneal macrophages in media containing L-arginine in the concentrations present in inflammatory lesions (less than 0.1 mM) enhances activation-associated functions. In contrast, culture in the higher L-arginine concentrations found in standard tissue culture media (0.4 to 1.2 mM) suppresses most macrophage functions (superoxide production, phagocytosis, and protein synthesis). An exception is the tumor cytotoxicity of Corynebacterium parvum-elicited macrophages which is enhanced by culture in supraphysiologic concentrations of L-arginine. Work reported here investigated the mechanisms for these L-arginine-dependent effects and, more specifically, the role of the recently described oxidative L-arginine deiminase pathway in the regulation of macrophage physiology. Overnight culture of resident or C. parvum-elicited peritoneal macrophages in media containing increasing concentrations of L-arginine (6 microM to 1 mM) resulted in: inhibition of electron transport chain activity (resident and C. parvum-elicited macrophages), increased lactate production (resident macrophages), and decreased ATP content (resident and C. parvum-elicited macrophages). In line with these findings, viability was markedly decreased after 2 days of culture when the initial L-arginine concentration was greater than or equal to 0.1 mM. As shown before, increasing media concentrations of L-arginine were associated with suppression of superoxide production and cytotoxicity in resident macrophages, and with reduced superoxide production and increased cytotoxicity in C. parvum elicited macrophages. All L-arginine-dependent metabolic and functional alterations, as well as the loss of viability, were prevented by NG-monomethyl-L arginine, a specific inhibitor of the oxidative L-arginine deiminase pathway. These results demonstrate that flux of L-arginine through the oxidative L arginine deiminase pathway results in the inhibition of oxidative metabolism in rat macrophages. This metabolic inhibition may, through alterations in the macrophage high energy phosphate stores, mediate the suppression of cell functions and result ultimately in cell death. PMID- 2584713 TI - Role of cell surface carbohydrate moieties in monocytic cell adhesion to endothelium in vitro. AB - Monocyte adhesion to endothelium represents the first step in the emigration of this leukocyte from blood to tissue during such pathologic and physiologic processes as atherosclerotic plaque development, wound healing, and inflammation. We have examined the role of carbohydrate moieties in the binding of mononuclear cells to endothelium in vitro. Wheat germ agglutinin (WGA) completely inhibited binding of the human monocytic cell line U937 to pig or human endothelial cells (EC). The inhibition was abolished by the presence of N-acetyl glucosamine, a preferred ligand for WGA. This sugar itself, however, had no effect on monocytic cell binding to EC, suggesting that WGA is inhibiting the cell-cell interaction by binding to a distinct sugar moiety. We tested a series of simple and phosphorylated sugars for the ability to inhibit U937 cell binding to EC. Two phosphorylated disaccharides, lactose-1-phosphate and maltose-1-phosphate, but not 14 other sugars, caused complete suppression of monocyte adhesion to EC. Among the inactive sugars were mannose-6-phosphate and fructose-1-phosphate, which have been shown by others to markedly suppress lymphocyte adhesion to EC. A nonionic detergent, n-octyl-beta-D-glucopyranoside (octyl glucoside), which contains a sugar group as a hydrophilic moiety, also inhibited U937 cell or human monocyte binding to human or porcine EC. The inhibition was observed at a nontoxic concentration of octyl glucoside and appeared to be due to an effect on the monocytic cell rather than the EC. When suboptimal doses of WGA and octyl glucoside were added in combination to the U937 cell-EC adhesion assay, the level of inhibition was greatly reduced when compared with either of the inhibitors alone, suggesting an interaction between these two blocking agents. Lactose-1 phosphate, but not octyl glucoside or WGA, blocked neutrophil adhesion to EC. In summary, our results indicate that specific cell surface carbohydrate groups are required for the adhesion of monocytes to the endothelium. PMID- 2584714 TI - Impaired macrophage activation in vitamin D3 deficiency: differential in vitro effects of 1,25-dihydroxyvitamin D3 on mouse peritoneal macrophage functions. AB - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to interact in vitro with mononuclear phagocytes. The purpose of this study was to determine the role of the steroid in macrophage activation in vivo. Peritoneal macrophages from normal and vitamin D3-deficient mice were obtained after i.p. injection of activating or eliciting agents. Cells obtained from vitamin D3-deficient mice exhibited defected capabilities to perform anti-tumor activities (cytostasis and cytolysis) and to form oxygen reduction products (H2O2 and O2-). On the other hand, the level of the lysosomal enzyme acid phosphatase was unaffected by vitamin D3 deficiency. In vitro, incubation of macrophages with 1,25(OH)2D3 enhanced their anti-tumor activities, but did not affect the cells' capacity to produce H2O2 and O2-, or acid phosphatase. Our results suggest that 1,25(OH)2D3 is essential for macrophage activation in vivo. However, in vitro, the hormone is only partially capable of affecting the macrophage functions, probably because of the maturation state of the cells. PMID- 2584715 TI - Regulated expression of proenkephalin A in normal lymphocytes. AB - The expression of proenkephalin A (PEA), a neuropeptide-encoding gene, was examined in normal rat lymphocytes. With the use of Northern blot hybridization analysis of total RNA, PEA mRNA was found in normal cells derived from spleen, lymph nodes, and bone marrow. Cell sorting of the two main fractions of B and T cells derived from the spleen revealed that PEA is expressed in normal B cells (sIg+). The expression of PEA mRNA was markedly enhanced after a short incubation (3 h) of cells with LPS or Salmonella typhimurium. This was not the case when these cells were incubated with Con A during the same period of time; whereas, in thymocytes the presence of PEA mRNA was exclusively dependent upon mitogenic stimulus (Con A) and could be detected after 24 h of in vitro incubation. Extracts of cells were also found to contain immune reactive enkephalins, indicating that the PEA mRNA is translated. These results support the concept that neuropeptides, such as enkephalins, have a role in the modulation of the immune response and may participate in the bidirectional communication between the nervous and immune systems. PMID- 2584717 TI - Immunogenicity of human hepatitis B virus P-gene derived proteins. AB - The frequency and specificity of antibodies to P-gene encoded proteins of human hepatitis B virus was tested in sera of acute and chronically infected patients with and without hepatocellular carcinoma (HCC). For antibody detection an immunoprecipitation gel assay was performed with radioactively labeled polypeptides produced by in vitro translation of RNA of different P-gene regions. Thus, five antigenic regions were identified. All anti-P antibody positive sera reacted with carboxy-terminal P-poly-peptides, a subset with polypeptides of the amino-terminal and middle region, and none reacted with P-protein derived from the most sequence variable region. Anti-P antibodies were detected at very high frequency in sera of acute (73%) and chronically infected patients without HCC (87%), but less often in HCC patients (27%). These data indirectly demonstrate the expression of most hepatitis B virus P-gene sequences and the immunogenicity of P-proteins in vivo. Moreover, they establish hepatitis B virus anti-P antibodies as a frequent serologic marker of infection and identify the carboxy terminal region of the P-protein(s) as immunodominant. PMID- 2584716 TI - Binding and release of C3 from Leishmania donovani promastigotes during incubation in normal human serum. AB - We have examined the nature and extent of C3 deposition on Leishmania donovani, strain 1S, clone 2D, promastigotes. Total molecules of C3 bound/parasite after 60 min was similar for parasites incubated in normal human serum, normal human serum adsorbed to remove natural antibody, or either serum source chelated with Mg-EGTA to limit activation to the alternative pathway. A comparison of parasites grown to early, mid, late-log or stationary phases revealed no difference in the extent and kinetics of C3 binding. C3 bound covalently to the parasite primarily through a hydroxylamine resistant (putatively amide) linkage. Of the bound C3, 75% was present as hemolytically inactive iC3b. Nearly 50% of the bound C3 was spontaneously released within 30 min at 37 degrees C. This spontaneous release was due to an unusual proteolytic cleavage event that released C3 from the C3 acceptor on the parasite surface. These results define and characterize the unusual features of C3 binding to L. donovani promastigotes during incubation in serum. PMID- 2584718 TI - Characterization of the thymus leukemia (TL) product encoded by the BALB/c T3c gene by DNA-mediated gene transfer. Comparison to the T13c product and BALB/c leukemia TL. AB - Using DNA-mediated gene transfer, we have studied the TL protein products encoded by both the T3c and T13c BALB/c genes. Biochemically, the proteins differed in their m.w. and pI points; serologically, although both molecules were recognized by TL alloantiserum, only the T13c protein was recognized by monoclonal TL antibodies. Interestingly, both proteins were serologically and immunochemically recognized by leukemia-specific TL.4 antiserum. The quantity of cell surface T13 was significantly greater than T3 possibly due to the less efficient splicing of T3 transcripts in the L cell nucleus; both genes directed the synthesis of cytoplasmic RNA containing an unspliced intron 3 as assessed by S1 analysis. In toto, the results suggest that T3c is similar or perhaps identical with the novel TL product previously identified on the surface of certain x-ray-induced BALB/c leukemias. PMID- 2584719 TI - Tumor necrosis factor mediates autocrine growth inhibition in a chronic leukemia. AB - Autocrine production of growth factors may contribute to the rapid and fatal proliferation of acute hematologic malignancies. We have investigated whether the more controlled growth of less aggressive malignancies such as chronic myeloid leukemia (CML) may be associated with autocrine production of growth inhibitory factors. TNF inhibits the growth of both normal and leukemic hemopoietic progenitor cells. We find that exogenous TNF reduces the viability and DNA synthesis of purified myeloid cells from patients with CML and inhibits myeloid colony formation by patient progenitor cells. However, unlike progenitor cells from normal donors, patient myeloid progenitor cells also constitutively express mRNA for TNF and secrete functional TNF protein in culture. This endogenous TNF impedes the growth of CML cells because anti-TNF mAb shown to neutralize bioactive human TNF increases CML cell DNA synthesis whereas non-neutralizing anti-TNF mAb has no effect. Production of TNF by CML cells is not associated with production of lymphotoxin (TNF-beta), IL-1 or IL-6. TNF-mediated autocrine growth inhibition may contribute to the maintenance of the stable, chronic phase of this disease and similar mechanisms may operate in other malignancies to limit tumor proliferation. Competition between autocrine growth promoting and inhibiting factors may underlie the observed differences in biologic behavior between acute and chronic malignancies. PMID- 2584720 TI - Tumor rejection mediated by transfection with allogeneic class I histocompatibility gene. AB - Non-self class I histocompatibility Ag can act as strong alloantigens and be recognized as distinct targets by CTL. To study the possibility of using allograft rejection to generate tumor-specific immunity, we have introduced an allogeneic class I histocompatibility gene, the H-2Kb gene, into a k haplotype tumor, K36.16, by DNA-mediated gene transfer. The K36.16 tumor grows readily and does not confer protective immunity in AKR mice. A total of 37 H-2Kb-transfected K36.16 clones (Kb/K36.16) was isolated and studied individually. The Kb/K36.16 clones were found to differ significantly in the amount of the exogenous H-2Kb antigens expressed on their cell surface. Moreover, as a result of the transfection, the level of expression of the endogenous H-2Dk Ag was also altered when compared to that of the parental K36.16 tumor cells. All the Kb/K36.16 clones that were positive for the H-2Kb Ag were rejected by the semisyngeneic AKR mice. Moreover, some of these Kb/K36.16 clones were also rejected by syngeneic (AKR x C57BL/10)F1 mice. In consequence of immunization with the Kb/K36.16 clones, the AKR and F1 mice were able to survive a subsequent challenge of the wild-type, unmodified, parental K36.16 tumor cells. More importantly, some of these Kb/K36.16 clones demonstrated an active and specific immunotherapeutic effect, and they were able to eradicate the growth of the parental K36.16 tumor cells in AKR mice. This observation therefore reinforces the feasibility of using DNA-mediated gene transfer as a molecular approach to abrogate tumor growth. PMID- 2584722 TI - Pathogenesis of autoantibody production in SLE. PMID- 2584721 TI - Characterization of syngeneic antiidiotypic monoclonal antibodies to murine anti human high molecular weight melanoma-associated antigen monoclonal antibodies. AB - Hybridization with murine myeloma cells P3-X63-Ag8.653 of splenocytes from BALB/c mice immunized with syngeneic anti-human high molecular weight melanoma associated Ag (HMW-MAA) mAb 149.53, 225.28, 763.74, and TP41.2 has resulted in the formation of antiidiotypic antibody-secreting hybridomas with a frequency ranging between 1.2% and 5.2%. No marked difference was detected in the frequency of antibody secreting hybridomas in the fusions generated from mice immunized with the four anti-HMW-MAA mAb, suggesting that the idiotopes expressed by each of them display similar immunogenicity in a syngeneic combination. The number of antiidiotypic mAb that did not inhibit the binding of immunizing mAb to melanoma cells was higher than that of those that died, suggesting that idiotopes not associated with the Ag-combining site are more immunogenic than those that are. The idiotopes recognized by mAb were not detected on a large panel of anti-HLA Class I mAb, anti-HLA Class II mAb, and anti-human melanoma-associated Ag mAb. The latter included also mAb that cross-inhibit the immunizing anti-HMW-MAA mAb. The idiotopes recognized by mAb were not detected on the isolated H and L chain of the immunizing anti-HMW-MAA mAb. Cross-blocking experiments with a selected number of antiidiotypic mAb identified three distinct idiotopes on mAb 149.53, 225.28, and TP41.2 and two on mAb 763.74. Three, 5, 2, and 5 antiidiotypic mAb to idiotopes within the Ag-combining site of mAb 149.53, 225.28, 763.74, and TP41.2, respectively, were tested for their ability to induce anti-HMW-MAA antibodies. Serological and immunochemical assays detected anti-HMW-MAA antibodies only in sera from BALB/c mice immunized with mAb MK2-23. Therefore, mAb MK2-23 can be classified as beta, while the remaining 14 can be classified as gamma. PMID- 2584723 TI - The difference between human C3F and C3S results from a single amino acid change from an asparagine to an aspartate residue at position 1216 on the alpha chain of the complement component, C3. PMID- 2584724 TI - Two-dimensional gels and amino acid hydrolysis data. PMID- 2584725 TI - Intra-uterine growth retardation. PMID- 2584727 TI - Nerve injuries in neonates. AB - A clinical study of 40 cases of nerve injuries in neonates with one-year follow up is presented. The total incidence of such injuries was 1.50%. Thirty-three cases sustained nerve injury due to obstetrical trauma and in 7 cases it was due to postnatal trauma like intragluteal injection and tight splintage. Almost in all cases there was history of prolonged or obstructed labour. Upper limb nerve injuries were commonest followed by facial palsy. Twenty-three cases (76%) showed complete recovery while 17% had partial and 7% no recovery at all. Hence nerve injuries are not uncommon in neonates. If managed properly the recovery is good. Intragluteal injection in the neonatal period should not be recommended. PMID- 2584726 TI - Maternal determinants of intra-uterine growth retardation. AB - Forty mothers with full term low birth weight babies and 30 age-matched mothers with full term normal birth weight babies were studied to find out the relative incidence of common maternal aetiological factors in the causation of intra uterine growth retardation (IUGR). Attention was focussed to find out the relevance of the following factors: Age of the mother, weight of the mother, incidence of toxaemias of pregnancy, haemoglobin and serum protein values. It was observed that there was a statistically significant correlation between the incidence of IUGR and maternal weight of less than 45 kg and of toxaemia of pregnancy. Also, there was an increased association of IUGR with decreased value of haemoglobin and serum protein in mothers. PMID- 2584728 TI - Ocular manifestations of rheumatoid arthritis. AB - One hundred and seven patients of definite rheumatoid arthritis were screened for the presence of ocular manifestations of which 21 (19.63%) were observed to have ocular changes. Of these keratoconjunctivitis sicca in 19 (17.7%) patients and episcleritis in one (0.93%) were attributable to rheumatoid arthritis. Bilateral retinal haemorrhage in one patient was due to grade 3 hypertensive retinopathy. Absence of posterior subcapsular cataract in 106 (99.06%) patients who did not receive corticosteroids supports the hypothesis that steroids are the aetiologic agents and not rheumatoid arthritis. PMID- 2584730 TI - Diabetes mellitus in geriatric females. AB - A study was carried out on 36 geriatric diabetic females (above 60 years). Marked exhaustion and significant loss of weight were common presenting complaints (60%) besides usual symptomatology. Only 25% patients were asymptomatic for diabetes. Generalised itching (20%) and pruritus vulvae (33.3%) were other common presenting complaints. Neuropathy was found to be the commonest complication being present in 77.7% patients, followed by retinopathy (50%) and nephropathy (27.7%). Hypertension was found to be associated in 44% patients and evidence of ischaemic heart disease was found in 42%. Development of nephropathy, retinopathy, neuropathy, and hypertension showed direct correlation with duration of illness ie, longer the history of diabetes higher was the incidence of complications. PMID- 2584729 TI - Pattern of paediatric solid malignant tumours in southern Orissa. AB - Twenty-nine cases of solid malignant tumours in paediatric age group were studied. The incidence of different tumours in order of frequency were lymphomas (37.9%), Wilms' tumour (24.1%), neuroblastoma (17.2%), soft tissue sarcoma (10.4%) and rare tumours (10.4%). Maximum number of tumours occurred in 1-5 years' age group. Male predominance was noted (male:female as 2.2:1). Among the lymphomas, non-Hodgkin's lymphoma outnumbered Hodgkin's lymphoma. Left kidney affection was seen more than the right kidney among cases of Wilms' tumours. Neuroblastomas presented commonly as abdominal masses. All the 3 cases of soft tissue sarcomas were embryonal rhabdomysoarcomas. Rare tumours encountered in the study were ovarian tumours (arrhenoblastoma), endodermal sinus tumours and hepatoblastoma. PMID- 2584731 TI - Meralgia paraesthetica. AB - Forty-four patients of meralgia paraesthetica presented with combination of symptoms mainly of numbness with loss of superficial sensation on the anterolateral aspect of a thigh were selected for the study. They responded well to local infiltration of hydrocortisone acetate and lignocaine hydrochloride which not only helped in diagnosis but also prevented the recurrence of symptoms in majority of cases. PMID- 2584733 TI - Asplenia syndrome. PMID- 2584732 TI - Psychic seizure. AB - Epilepsy is a fairly common disease. Various types of epilepsy, e.g., grand mal, petit mal, Jacksonian, akinetic, and myoclonic are usually encountered. An atypical type, presenting only with psychiatric symptoms is rarely found. A report of one such case is presented. PMID- 2584734 TI - Primary carcinoma of the fallopian tube with torsion. PMID- 2584735 TI - Vascular hamartomas in infancy and childhood. PMID- 2584736 TI - Palpitation: a useful clinical clue. PMID- 2584737 TI - Leukotrienes C4 and D4 as potent mitogens for cultured human neonatal melanocytes. AB - Arachidonic acid and its metabolites (eicosanoids) are membrane-derived inflammatory mediators with a diverse set of biologic properties affecting numerous cells and organ systems, including the skin. They have been implicated in the pathogenesis of inflammatory skin disease and post-inflammatory hyperpigmentation. We have studied the ability of arachidonic acid, prostaglandin D2, prostaglandin E2, leukotriene B4, leukotriene C4, leukotriene D4, and leukotriene E4 to enhance the growth of cultured human melanocytes. Of these compounds, only leukotriene C4 and leukotriene D4 were capable of stimulating melanocyte proliferation. In addition, cultured melanocytes metabolized leukotriene C4 to leukotriene E4 with greater than 60% conversion in less than three hours. Melanocytes grown on suboptimal media (doubling time 12-20 days) respond in a dose-dependent fashion to leukotriene C4, with a significant difference from control noted at 28 days with a concentration of LTC4 of 30 nM and a doubling time of 5-8 days. We feel that leukotriene C4 and D4 could play an important role in post-inflammatory melanocyte hyperplasia. PMID- 2584738 TI - The origin of alkanes found in human skin surface lipids. AB - Lipids extracted from human skin contain variable amounts of paraffin hydrocarbons. Although the composition of these alkanes strongly resembles petroleum waxes, it has been proposed that they are biosynthetic products of human skin. To investigate this question, skin surface lipids from 15 normal subjects were analyzed for the amount and composition of alkanes, using quantitative thin-layer chromatography and quartz capillary gas chromatography. The alkanes were found to constitute 0.5% to 1.7% of the skin lipids. Subjects differed greatly in the chain length distribution of their alkanes between 15 and 35 carbon atoms, and in the relative amounts of normal alkanes (like those in petroleum waxes) and branched chain alkanes (like those in petroleum lubricating oils). In 6 subjects, the alkane content of cerumen from each ear was examined to investigate whether alkanes arrive at the skin surface by a systemic route or by direct contact with environmental surfaces. No trace of alkanes was found in 11 of the 12 cerumen samples. Using a tandem accelerator mass spectrometer for carbon-14 dating, a combined sample of the skin surface alkanes was found to have a theoretical age of 30,950 years, similar to that of a sample of petrolatum. These analyses indicate that the alkanes found on the surface of human skin are mixtures of a variety of petroleum distillation fractions that are acquired by direct contamination from the environment. PMID- 2584739 TI - The sensitivity of Langerhans cells to simulated solar radiation in basal cell carcinoma patients. AB - The role of Langerhans cells (LC) in host resistance against the induction and growth of nonmelanoma skin cancers is still obscure. The purpose of this study was to investigate the sensitivity of LC to simulated solar radiation in patients with basal cell carcinoma (BCC). Thirty-four patients (31-74 years old) with at least one histologically diagnosed BCC on a sun-exposed area and 21 healthy volunteers (29-62 years old) were included in the study. Patients and control subjects were given 10 graded doses of simulated solar UV radiation (10-75 mJ/cm2) on the lower back using a 12S solar simulator with a WG 320 filter. Twenty-four hours later, the minimal erythema dose (MED) was determined and shave biopsies were taken from the site given 1.25 X MED and from adjacent, unirradiated skin. Epidermal sheets were stained for LC using the ATPase method. The mean value of the MED of the BCC patients was 25 +/- 2 mJ/cm2 and that of controls was 29 +/- 3 mJ/cm2 (p greater than 0.05). The number of ATPase+ LC was significantly decreased (p less than 0.05), and their morphology was altered in the irradiated skin of nearly all individuals. However, there was no significant difference in the average reduction of LC in the patients (32% +/- 3%) compared with that of control subjects (32% +/- 4%). The depletion of LC ranged from 0% to 74% in different individuals, all of whom were given 1.25 MED. Furthermore, no correlation was found between the percentage decrease in ATPase+ cells and the dose of UV radiation required to produce erythema. Our results indicate that the ability of UV radiation to cause erythema was unrelated to the magnitude of its effects on LC number or morphology. Second, the morphologic alterations of LC in BCC patients after UV irradiation do not differ from those observed in normal individuals. Third, as a group, patients with BCC do not have a significantly lower MED than cancer-free subjects. PMID- 2584740 TI - The immunogenetic relationship between anti-Ro(SS-A)/La(SS-B) antibody positive Sjogren's/lupus erythematosus overlap syndrome and the neonatal lupus syndrome. AB - We have described previously the clinical features of a unique group of anti Ro(SS-A) antibody positive Sjogren's patients who have cutaneous features of lupus erythematosus, most commonly subacute cutaneous lupus erythematosus, defined as the Sjogren's/lupus erythematosus overlap syndrome. Three of these patients are also mothers of infants with the neonatal lupus erythematosus syndrome, characterized by cutaneous lesions resembling subacute cutaneous lupus erythematosus or congenital heart block. Patients with Sjogren's/lupus erythematosus overlap syndrome, subacute cutaneous lupus erythematosus, and mothers of infants with the neonatal lupus syndrome characteristically have autoantibodies to Ro(SS-A), and in many cases, La(SS-B) antigens. The present study was designed to test the hypothesis that anti-Ro(SS-A)/La(SS-B) positive Sjogren's/lupus overlap patients and mothers of infants with neonatal lupus erythematosus syndrome are immunogenetically homogenous and closely related. We report a strong association with HLA-B8, DR3, DQw2, and DRw52 phenotypes and the HLA-B8, DR3, DQw2, DRw52 extended haplotype in both patient cohorts. Furthermore, we describe disease associations with HLA-DR3/DRw6 heterozygotes in both patient groups. These data demonstrate that anti-Ro(SS-A)/La(SS-B) positive Sjogren's/lupus overlap patients and neonatal lupus syndrome mothers are immunogenetically closely related to each other and appear to be more closely related to both primary Sjogren's syndrome and subacute lupus erythematosus, than to classical systemic lupus erythematosus. PMID- 2584741 TI - A fully differentiating epidermal model with extended viability: development and partial characterization. AB - A highly differentiated porcine skin organ culture model has been developed for future investigations of membrane-coating granules (MCG) and their role in epidermal differentiation. In contrast to many previous systems, cultures do not undergo necrosis of the upper epidermis or display dermo-epidermal separation, but survive for at least 3 weeks, at which time mitotic cells are still evident. Although rete projections are gradually smoothed out and the viable epidermis thins at a rate of approximately 0.35 cells per day, the stratum corneum gains approximately 1.5 corneocytes per day. Furthermore, at 3 weeks all the major differentiation markers are expressed, including keratohyalin granules, MCG, and an orthokeratotic stratum corneum. The system is inexpensive, simple to establish, and does not require elevated oxygen levels. The main requirements are 1) the use of Dulbecco's minimal essential medium supplemented with 2) hydrocortisone (100 micrograms/ml), 3) growth at an air/liquid interface, and 4) attached connective tissue. The further addition of vitamin C (300 micrograms/ml) and/or bovine serum albumin (2 mg/ml) offered no obvious advantage. Degeneration of organ cultures in standard cell culture media was discovered to be caused by fetal bovine serum (FBS). FBS-induced degeneration was not prevented by adding any of the supplements tested, or the inclusion of 3T3 fibroblasts, even when culturing at an air/liquid interface. Complete submersion rapidly killed specimens, presumably through oxygen starvation. The ability to maintain a fully keratinizing system for several weeks, in a totally chemically defined medium, will prove valuable for research not only into the role(s) of MCG in epidermal biology but also studies of desquamation and epidermal differentiation. PMID- 2584742 TI - Impairment of enzymic and nonenzymic antioxidants in skin by UVB irradiation. AB - Antioxidants may play a significant role in ameliorating or preventing photobiologic damage in skin that could lead to cutaneous disorders such as cancer and premature aging. The objective of this study was to assess the acute cutaneous enzymic and nonenzymic antioxidant response to a single exposure of large fluence (300 mJ/cm2) ultraviolet radiation (greater than 280 nm) in hairless mice. This treatment caused an immediate and statistically significant inhibition of glutathione reductase and catalase activity. Glutathione peroxidase and superoxide dismutase were not affected. Glutathione levels decreased and, conversely glutathione disulfide concentrations increased. A slight depletion of the total glutathione was observed, while the content of total ascorbic acid did not change. The lipophilic antioxidants alpha-tocopherol, ubiquinol 9 and ubiquinone 9 also decreased significantly, and the concentration of malondialdehyde remained constant. The free radical scavenging activity of epidermis, as assessed by reduction of the stable, cationic nitroxide radical [2,2,6,6-tetramethyl-1-piperidinoxy-4-(2',4',6'-trimethyl) methylpyridinium perchlorate] was considerably inhibited. The study indicates that immediately after exposure to a large fluence of ultraviolet radiation the enzymic and nonenzymic antioxidant capacity of skin decreases significantly. PMID- 2584743 TI - Enhancement of hydrocortisone permeation of human and hairless mouse skin by 1 dodecylazacycloheptan-2-one. AB - The influence of 1-dodecylazacycloheptan-2-one (Azone) on the in vitro permeation of hairless mouse skin and human epidermis by hydrocortisone was studied as a function of the amount of Azone solubilized and/or emulsified into aqueous media applied to the membranes using the infinite-dose technique. The permeability enhancing effect of Azone increases with increasing Azone total concentrations until 0.1% is reached with mouse skin and 0.01% is reached for human epidermis. Thereafter, permeabilities for both tissues drop systematically. The maximally enhanced permeability in mouse skin approached that for mouse skin stripped of its stratum corneum. The peak permeability in human epidermis is an order of magnitude smaller than for mouse skin with the duration of Azone treatment required to achieve the full effect in human epidermis being twice that for mouse skin (approximately 20 h vs approximately 12 h). Thus, there is a profound difference in Azone's action on these two tissue types. It was also established that the affinity of an enhancer for a permeant drug can significantly offset its ability to enhance permeability. Specifically, hydrocortisone was found to partition significantly into the Azone-rich phase of the emulsion, lowering its concentration (and its thermodynamic activity) in the continuous aqueous phase and thereby reducing its flux through the skin. This physiochemical effect was profound enough to nullify the intrinsic permeability-enhancing effect of Azone as the total Azone concentration was raised to 10%. PMID- 2584744 TI - An immunohistochemical and immunoelectron microscopic study of the ontogeny of rat Langerhans cell lineage with anti-macrophage and anti-Ia monoclonal antibodies. AB - An immunohistochemical study with anti-macrophage and anti-Ia monoclonal antibodies was performed to clarify the relationship between Langerhans cells (LC) and indeterminate cells (IC) in rat epidermis both in adulthood and in the fetal stage. On immunoelectron microscopy, a mouse anti-rat macrophage monoclonal antibody, TRPM-1, recently produced by us, reacted with IC and some LC in adult rat skin. Ontogenic study revealed that TRPM-1-positive cells first appeared in the epidermis of fetal rat heads on Day 17 of gestation and then spread caudally along the anterior-posterior axis. On Day 20 of gestation, when the distribution of the TRPM-1-positive cells over body surface became even, Ia-positive cells appeared in the epidermis and began to increase in number. Ia-positive cells with Birbeck granules were found on Day 21 of gestation. These results indicate that. TRPM-1-positive IC matured into Ia-expressing LC after being exposed to microenvironmental change during the perinatal period. The number of Ia-positive cells exceeded that of TRPM-1-positive cells at around 5 d after birth. Afterwards, there were more dendritic Ia-positive cells found in the interfollicular areas than TRPM-1-positive ones. However, local concentrations of the TRPM-1-positive IC in the follicular infundibula were frequently found in the fetal stage and occasionally in adulthood. These TRPM-1-positive cells in the follicular infundibula were thought to be a precursor pool in the epidermis for LC. PMID- 2584745 TI - Development of human fetal skin transplanted to the nude mouse. AB - Thirty-five human fetal skin (HFS) grafts were transplanted to nude mice for 7 to 70 d and evaluated histologically with 64 biopsies. The estimated gestational ages (EGA) of the grafts at the time of the transplantation ranged from 8 to 19 weeks. The maturation of the engrafted fetal skin was evaluated by assessing epidermal, dermal, and appendage development. Within the nude mouse, the HFS demonstrated progression in stratification and maturation of the epidermis. The dermis increased in depth, adding fibrovascular stroma and adipose tissue. The appendages demonstrated invagination, differentiation, and progression of organogenesis. Subcutaneously placed grafts showed the same rate of HFS development as HFS in utero. The grafts transplanted to the surface of the nude mice and exposed to air demonstrated an acceleration of development. We conclude that HFS transplanted to the nude mouse is an effective in vivo model for maintaining and altering HFS maturation. PMID- 2584746 TI - Long-term culture of fibroblasts in contracted collagen gels: effects on cell growth and biosynthetic activity. AB - The purpose of these studies was to analyze the consequences of long-term collagen gel contraction on fibroblast growth and metabolic activity. After 4 weeks, floating gels were 98% contracted, and attached gels were 94% contracted. During this culture period, fibroblasts in floating gels regressed significantly compared to fibroblasts in attached gels, although the cells remaining in the floating gels were viable. In attached gels, fibroblasts were bipolar; whereas in floating gels, fibroblasts were stellate. Therefore, differences between survival of fibroblasts in attached and floating collagen gels might depend on cell shape. Similarly, extracellular matrix organization and its influence on cell shape might control fibroblast proliferation in granulation tissue. During long-term culture of fibroblasts in contracted collagen gels, 70%-80% of the starting collagen was degraded. Collagen synthesized by cells in 4-d cultures was mostly procollagen secreted into the medium. On the other hand, collagen synthesized in 4-week cultures was processed to alpha (I) chains and incorporated into the matrix. There also were other differences between the proteins synthesized by fibroblasts after short-term and long-term culture in contracted gels. These findings show that fibroblasts in long-term collagen gel cultures express unique growth and biosynthetic characteristics. PMID- 2584747 TI - Preparation of model membranes for skin permeability studies using stratum corneum lipids. AB - Liposomes were prepared from stratum corneum lipids consisting of epidermal ceramides (55% by weight), cholesterol (25%), free fatty acids (15%), and cholesteryl sulfate (5%). Multiple lamellae were formed by air-drying the liposomal suspensions on hydrophilic filter disks, and water permeabilities through these filter-supported lamellae were measured using a diffusion cell. Ultrastructure of the lipid lamellae was characterized by scanning and thin section electron microscopy. Water flux data and ultrastructure of the model membranes are discussed in relation to stratum corneum, the horny layer of the epidermis that constitutes the epidermal barrier. PMID- 2584748 TI - Effect of enzyme digestion on anionic sites and charge-selective permeability of dermo-epidermal junction. AB - To study components of anionic sites on the lamina densa of the dermo-epidermal junction (DEJ) and to assess the effect of removal of sialic acid or glycosaminoglycans on its charge-selective permeability, epidermal sheets, whose dermis had been removed by treatment with dithiothreitol, were digested with heparitinase, chondroitinase ABC, hyaluronidase, or neuraminidase. They were then stained with polyethyleneimine for demonstration of the anionic sites or incubated in a medium containing native anionic ferritin for tracer experiments. The anionic sites were completely removed after heparitinase digestion. Although the numerical density of the sites was not altered, their electron density was decreased after chondroitinase ABC digestion. The other enzymes had no effect on the sites. In the tracer experiments, heparitinase or neuraminidase increased the number of tracer molecules penetrating into the lamina lucida of the epidermal sheet, while the other enzymes had no effect on it. These data indicate that heparan sulfate, which is a main component of the anionic sites, plays an important role in the charge-selective permeability of the DEJ, whereas chondroitin sulfate, which seems to be contained in the sites, does not, probably because of its small amount. These data also indicate that sialic acid, which is not a main component of the anionic sites demonstrated with the cationic probe, has a role in the permeability function. PMID- 2584749 TI - Cerebrospinal fluid endotoxin levels in children with H. influenzae meningitis before and after administration of intravenous ceftriaxone. AB - Total, cell-free, and cell-bound endotoxin and bacterial density were measured in cerebrospinal fluid (CSF) of 22 children with Hemophilus influenzae meningitis. Also the effect of ceftriaxone on CSF endotoxin levels was investigated in eight patients by reexamining their CSF 2-6 h after the initial dose. Initial CSF bacterial density correlated with initial CSF endotoxin levels (P less than .001). Ceftriaxone induced a marked increase of free endotoxin in CSF, from an initial (mean +/- SE) 0.75 +/- 0.21 to 1.29 +/- 0.23 log10 ng/ml (P less than .01). This increase correlated positively with the number of bacteria killed in the CSF (P less than .01). The increase in free endotoxin was associated with an increase in mean CSF lactate levels from 8.5 to 9.7 units/l (P less than .05) and mean lactate dehydrogenase levels from 102 to 180 mmol/l (P less than .02) and a decrease in mean CSF glucose from 1.17 to 0.46 mmol/l (P less than .05). Initial CSF total endotoxin concentrations correlated both with the Herson-Todd clinical severity score (P less than .001) and with the number of febrile hospital days (P less than .001). These findings suggest that highly bactericidal agents initially lead to release of free endotoxin from gram-negative organisms into CSF, with associated enhanced inflammatory response by the host. PMID- 2584751 TI - Mycobacterium avium and Mycobacterium intracellulare infections in patients with and without AIDS. AB - A genetic probe (Gen-Probe) was used to evaluate potential epidemiologic and susceptibility differences of Mycobacterium avium complex (MAC) strains isolated from 154 patients with and without the acquired immunodeficiency syndrome (AIDS). Genetic analysis revealed that 98% of the 45 patients with AIDS harbored only M. avium regardless of the anatomic or geographic source of the isolate; in contrast, approximately 40% of MAC isolates recovered from 109 patients without AIDS were M. intracellulare. Most M. intracellulare of respiratory origin recovered from patients without AIDS were involved in infectious processes. When 95 MAC isolates (M. avium, n = 53; M. intracellulare, n = 42) were evaluated for in vitro susceptibility to primary or secondary antimycobacterial drugs, significant differences were noted. M. intracellulare was more susceptible to streptomycin, rifampin, and ethambutol than M. avium; the converse was true for ethionamide. The results of this study suggest potentially important differences in disease spectrum and in vitro susceptibility profile for M. avium and M. intracellulare. PMID- 2584750 TI - A specific and sensitive assay for the Lyme disease spirochete Borrelia burgdorferi using the polymerase chain reaction. AB - A highly specific and sensitive assay for Borrelia burgdorferi, the causative agent of Lyme disease, was developed using the polymerase chain reaction (PCR). The target DNA sequence was of chromosomal origin and conserved, by hybridization analyses, among all strains of B. burgdorferi tested but was not present in the most closely related member of the genus, B. hermsii. The PCR assay developed from this sequence reacted with 17 of 18 strains of B. burgdorferi but not with any other Borrelia species tested. The assay was sensitive to fewer than five copies of the B. burgdorferi genome, even in the presence of a 10(6)-fold excess of eukaryotic DNA. This assay should greatly facilitate the accurate diagnosis of Lyme disease and provide a means with which to investigate the pathogenesis, transmission, and basic biology of B. burgdorferi. PMID- 2584752 TI - Urbs in rure: human immunodeficiency virus infection in rural Tennessee. AB - Although the AIDS Commentaries published over the past 18 months have focused on clinical questions relevant to all practicing infectious diseases physicians, they have emphasized clinical information gathered from the large epicenters of the epidemic. We need to remember that clinicians dealing with HIV-infected patients outside metropolitan areas may face problems that are unique. For example, fighting the stigma of AIDS in a low-prevalence population may be as important an issue as treating pneumocystic pneumonia. In this AIDS Commentary, Drs. Abraham Verghese, Steven L. Berk, and Felix Sarubbi of the Veterans Administration Medical Center, East Tennessee State University and describe their experiences in such an environment, discuss some of the problems they've faced, and offer suggestions about what physicians and health officers need to do to prepare for the inevitable spread of AIDS to rural communities. PMID- 2584753 TI - Influence of magnesium concentration on production of exoprotein and beta lactamase by Staphylococcus aureus and Staphylococcus hemolyticus. AB - Earlier investigations demonstrated that production and secretion of toxic shock syndrome toxin-1 (TSST-1) and total exoprotein by strains of Staphylococcus aureus were maximal when magnesium ion was limiting and diminished when the concentration of magnesium increased. This investigation studied the influence of magnesium concentration on production of total exoprotein and beta-lactamase by strains of S. aureus and Staphylococcus hemolyticus, isolated from the genital tracts of women. These strains were resistant to penicillins. Each organism was incubated in chemically defined medium with various concentrations of magnesium, and total exoprotein production and beta-lactamase activity in supernatants were determined. In all strains, total exoprotein production and beta-lactamase activity per bacterial cell were markedly increased in the presence of low concentrations of magnesium. When the concentration of magnesium was elevated, production of total exoprotein and beta-lactamase was decreased. Therefore, magnesium-deficient strains of S. aureus and S. hemolyticus may secrete more exoproteins and be more resistant to beta-lactam drugs than when magnesium is not limiting. PMID- 2584754 TI - Anaerobic bacterial bacteremia: 12-year experience in two military hospitals. AB - Clinical and microbiologic data of 296 patients with anaerobic bacteremia were reviewed. Anaerobes were isolated with aerobic or facultative bacteremia in 23 instances. The Bacteroides fragilis group accounted for 148 (70%) of 212 isolates of Bacteroides species. B. fragilis accounted for 78% and B. thetaiotaomicron for 14%. Among other species, there were 20 (6%) Fusobacterium organisms, 63 (18%) Clostridium isolates, and 53 (15%) anaerobic cocci. Seventy-five patients died: 40 had B. fragilis group isolates - B. fragilis, 28, and B. thetaiotaomicron, 8 - and 21 had Clostridium organisms isolated. The primary portals of entry were the gastrointestinal tract (42%), decubiti and gangrene (10%), the female genital tract (8%), and the oropharynx (7%). The gastrointestinal tract, decubiti, and gangrene were the predominant sources for B. fragilis and Clostridium organisms, the female genital tract and oropharynx for anaerobic cocci and Fusobacterium species, and the oropharynx for pigmented Bacteroides. Foreign body was associated with Propionibacterium acnes and Clostridium species. Factors predisposing to bacteremia were abscesses, 53; malignancy, 51; surgery, 30; and intestinal obstruction or perforation, 27. PMID- 2584755 TI - Characterization of a thiol proteinase in Giardia lamblia. AB - Sonicated preparations of Giardia lamblia hydrolyze a variety of protein substrates including human immunoglobulin. Activity is increased by thiol activating agents and inhibited by thiol proteinase inhibitors. About 55% of activity remains in the soluble fraction after high-speed centrifugation, and pretreatment with a nonionic detergent results in increased soluble activity. This suggests that the enzyme is membrane bound or associated with subcellular particles. Activity elutes as a major peak at 38,000 molecular weight by calibrated sieve chromatography. The favored sites of enzymatic cleavage of IgA1 are between the CH2 and CH3 domain and near the hinge region of the heavy chain. Similar cleavage patterns were identified using sonicated preparations of Entamoeba histolytica and Trichomonas vaginalis. PMID- 2584756 TI - Vibrio cholerae wound infection acquired in Colorado. PMID- 2584757 TI - Deficient interferon-alpha production but normal natural killer cell activity in an AIDS patient with HIV-2 infection. PMID- 2584758 TI - Circulating lymphokine levels in the chronic fatigue syndrome. PMID- 2584759 TI - Intravenous metronidazole and Clostridium difficile-associated diarrhea or colitis. PMID- 2584760 TI - False-positive serology of rickettsial disease in parenteral drug addicts. PMID- 2584761 TI - Evidence of immunologic cross-reactivity between hemolysins of Vibrio hollisae and Vibrio parahaemolyticus demonstrated by monoclonal antibodies. PMID- 2584762 TI - Eye involvement in cerebral malaria. PMID- 2584764 TI - Vibrio gastroenteritis in Louisiana: a prospective study among attendees of a scientific congress in New Orleans. AB - The incidence of diarrhea associated with infection by Vibrio species was investigated among attendees at the 1986 Interscience Conference on Antimicrobial Agents and Chemotherapy held in New Orleans. Twelve percent of respondents reported diarrhea; the risk of diarrhea was significantly higher in those who ate raw or cooked oysters (relative risk = 1.5, P = .005). At least one Vibrio species was recovered from 51 (11%) of 479 persons submitting stool specimens; however, only 15 (29%) of those with a positive stool culture also reported diarrhea. Of the five Vibrio species identified, V. parahaemolyticus was most common and was most strongly associated with diarrhea. V. cholerae serogroup O1 was not isolated despite the occurrence of a cholera outbreak during the same time period in Louisiana. Cultures of raw and cooked seafood served in local restaurants yielded five different Vibrio species. Although asymptomatic passage of Vibrio organisms was common among persons eating seafood, the risk of Vibrio gastroenteritis was low. PMID- 2584763 TI - Characterization of the transcripts of hepatitis D and B viruses in infected human livers. AB - To examine the replication of hepatitis D virus (HDV) and its interactions with helper hepatitis B virus (HBV), the RNA of both viruses was analyzed in liver biopsy tissue obtained from six patients with past or present hepatitis. In four of five hepatitis B surface antigen (HBsAg) carriers, the RNA genome of HDV was found in the liver. Further, the complementary RNA species as replication templates of HDV genomes documented in previous animal studies were confirmed. Within the livers of four HBsAg carriers, the transcription of HBV was absent or incomplete, however, in the patient without HDV RNA, the HBV genes expressed accurately and actively. This may account for the previously observed HBV suppression by concomitant HDV infection. PMID- 2584765 TI - Epidemiology and spectrum of Vibrio infections in a Chesapeake Bay community. AB - The clinical and epidemiologic features of vibrio infections occurring over 15 y in a hospital adjacent to the Chesapeake Bay were examined. Microbiologic techniques included the use of thiosulfate citrate bile salts sucrose (TCBS) medium on all stool specimens. Among 40 vibrio isolates from 32 patients, eight species were identified: V. parahaemolyticus (16), V. vulnificus (10), non-O1 V. cholerae (7), V. mimicus (3), V. hollisae (1), V. fluvialis (1), V. alginolyticus (1), and an unnamed halophilic vibrio. Sources included stool (13), wound (11), sputum (3), ear (3), bone (1), and gallbladder (1). While illnesses were diverse, they were relatively mild and self-limited with no mortality. The mild clinical spectrum and especially lack of mortality are in sharp contrast to the findings of previous reports. Even with the proximity to the bay and use of optimal isolation techniques, the demonstrated incidence of vibrio infections was low (1.6/100,000/y). The routine use of TCBS medium, which has been advocated for high-risk areas, was not cost-effective. PMID- 2584766 TI - Otitis media in children. I. The systemic immune response to nontypable Hemophilus influenzae. AB - Twenty-one infants experienced 29 episodes of otitis media with effusion caused by nontypable Hemophilus influenzae (NTHI) during 2 y of observation. Bactericidal antibody was detected in acute serum of 26% of the subjects at a mean titer of 0.8 +/- 0.3 (log2) and was observed in convalescent serum of all of the individuals at a mean titer of 4.0 +/- 0.3 (log2, P less than .001). The serum bactericidal antibody response was not age-dependent (r = .08, P greater than .05). Serum concentrations of bactericidal antibody remained stable for the entire observation period in 90% of the children. The presence of serum bactericidal antibody correlated significantly with a reduction in the number of bacteria present in the middle ear fluid (P less than .025). Eight children experienced a second episode of otitis media with effusion caused by a different serotype of NTHI. All those who lacked bactericidal antibody against the organism causing the second episode possessed bactericidal antibody against the first strain at the time of the second episode. These data suggest that the immune response to NTHI in otitis media with effusion is type-specific. The occurrence of second episodes of otitis media with effusion due to different strains of NTHI in the face of preexisting heterologous bactericidal antibody suggests a lack of NTHI in the face of preexisting heterologous bactericidal antibody suggests a lack of cross-protection. PMID- 2584767 TI - [Results of pulmonary resection for metastatic lung tumors]. AB - The results of pulmonary resection for metastatic pulmonary lesions in our institution are reviewed. Over the period of ten years 43 patients underwent 46 thoracotomies with a 5 years survival rate of 40.8%. The most significant predictors of survival were type of primary tumor, number of lesions removed and disease-free interval, while there were no statistically significant difference in survival rates between partial resection and lobectomy. Recurrence in the early postoperative period was often observed in the patients with bilateral pulmonary metastases and their 5 years survival rate was as low as 21.9%. Though multiple lung metastases is not contraindication for pulmonary resection, we should be prudent to operate for those patients with multiple lung metastases. Our results suggest that the patient with solitary lesion, long disease-free interval and no metastases to mediastinal lymph nodes is the best candidate for resection of the metastatic pulmonary lesions. PMID- 2584768 TI - [Comparative study of the protective effects of a cold potassium cardioplegic solution verses the Collins solution in the preservation of canine hearts for 24 hours by simple immersion method]. AB - This study was undertaken to compare the protective effects of a cold potassium cardioplegic solution (K+:23 mEq/l, Na+:25.2 mEq/l) versus the Collins solution (K+:115 mEq/l, Na+:10 mEq/l) on the preservation of isolated canine hearts for 24 hours by simple immersion. To assess the viability of the preserved hearts, recovery of left ventricular function, myocardial water content and myocardial ultrastructures were evaluated before and after preservation. Isovolumic left ventricular function was evaluated with an intra-ventricular balloon method using a preparation of an isolated, blood-perfused heart. The cardioplegic solution group (n = 9) showed significantly better recovery results of pressure developed in the left ventricular (84-76 vs. 35-37%) and dp/dt (90-52% vs. 44-39%) as compared to the Collins solution group (n = 13). Compliance of the left ventricle was well maintained in the cardioplegic solution group. The Collins solution group showed a significant increase of myocardial water content and a remarkable decrease in compliance of the left ventricle after preservation. The quantitative evaluation results of the mitochondrial injury (mitochondria score) found through electron microscopy revealed that the mitochondria of the cardioplegic solution group were less injured as compared to those of the Collins solution group. We concluded that our cold potassium cardioplegic solution offers superior protective effects on the preservation of the heart by simple immersion as compared to the Collins solution. PMID- 2584769 TI - [Development and evaluation of ventricular assist blood pump to salvage patients with profound heart failure]. AB - One of the most important characteristics of a ventricular assist device (VAD) is good antithrombogenicity such that the circulating blood does not clot on the surface even when the bypass flow through the device is reduced at the time of weaning-off. A pneumatic and diaphragm-type VAD with excellent antithrombogenicity was developed for clinical use. The pump is made of Japanese made segmented polyether polyurethane and the maximum output is 7.0 L/min. If the bypass flow was maintained above 2.0 L/min during early postoperative period, thrombus formation was rarely observed even when the flow rate decreased afterwards in chronic animal experiments using 30 goats. Experimental analyses suggested that a biolization mechanism of the material surface covered by absorbed plasma protein might play a major role in the establishment of antithrombogenicity of the pump. No mechanical failure, thrombosis, calcification, and complication in experimental animals occurred when the VAD manufactured under our good quality control system was driven adequately. These results proved that the VAD could be used reliably for at least 3 months. In conclusion, the VAD is safely applicable to clinical cases and contributes to treatments of profound heart failure patients. PMID- 2584770 TI - [Surgical repair and late problem for Ebstein's anomaly--surgical cases with severe tricuspid stenosis or regurgitation]. AB - In this report, we described our surgical experiences of Ebstein's anomaly with severe tricuspid stenosis (TS) or regurgitation (TR). Long-term clinical assessments and late problems of the treatment were also mentioned. From 1953 to 1988, a total of 2850 patients with congenital heart malformation underwent surgery in our hospital. During this period, 32 patients with Ebstein's anomaly were admitted, and surgical treatment was performed in 10 of these patients. Thus, the surgical treatment of Ebstein's anomaly took only 0.35% of total surgeries of congenital heart diseases. According to Takayasu's classification of Ebstein's anomaly, 6 of our these patients were classified into TS, and 4 into TR type. The operative methods were shunt operation in 3 patients, plication in 2 patients and tricuspid valve replacement (TVR) in 5 patients. One patient was died during the operative course of Glenn's procedure. Other 9 patients are alive and the longest follow-up period is 18 years at this moment. In the remaining two patients with shunt operation, Blalock-Taussig's procedure completely diminished their polycythemia. In the cases of TVR, the replaced valve was sutured to the right atrium in 2 patients with TS, true annulus in 2 patients with TR, valve remnant in one patient with TR type. Delayed cardiac tamponade occurred in 2 patients and calcification of Xenograft valve was observed at 8 years after the surgery in one patient with TVR. Although the hemodynamics did not improve immediately just after open heart surgery, cardio-thoracic ratio reduced and clinical symptoms were improved remarkably throughout the long-term follow up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584771 TI - [Studies on optimal reperfusate temperature following hypothermic ischemic arrest in the isolated rat hearts]. AB - This study was undertaken to evaluate the optimal reperfusate temperature during early reperfusion period for 10 min of non-working mode followed by 20 min of normothermic working mode in the isolated hypothermic ischemic (20 degrees C, 60 min) rat hearts. The reperfusate temperature was selected 20 degrees C (group A) and 30 degrees C (group B) as a hypothermic reperfusion, and 37 degrees C (group C) for normothermia. Functional recovery of aortic flow rate (AFR), heart rate (HR), peak systolic pressure (PSP), coronary flow (CF), and rate pressure product was compared among three groups as well as myocardial biochemical (adenosine triphosphate (ATP), creatine phosphate (CP)) and ultrastructural change. During non-working reperfusion, HR and CF showed significant positive correlation to reperfusate temperature. At the end of 10 min of non-working reperfusion, myocardial creatine phosphate (CP) significantly increased in all groups beyond the pre-ischemic level, however CP in the group A and B was significantly better compared to that in the group C. And myocardial ATP was better recovered near to the pre-ischemic level in the hypothermic groups compared to the group C without significant recovery, being significantly different between group A and C. The integrity of mitochondrial ultrastructure was also well maintained in group A compared to group C. At the end of normothermic reperfusion in the working mode for 20 min, percent recovery of AFR was 85.1% (B), 73.3% (A) and 70.3% (C), and percent recovery of rate pressure product was 92.5% (A), 89.1% (B) and 78.6% (C) with significant difference between the hypothermic and the normothermic groups. PSP, CF and HR recovered without significant difference among three groups. Myocardial ATP and CP declined significantly during 20 min of working reperfusion to the same level as those of three groups. CP only in group C was significantly lower than pre-ischemic level, although ATP in all groups at the end of reperfusion was significantly lower than the pre-ischemic level. These data suggest that hypothermic (20 degrees C, 30 degrees C) reperfusion seemed to provide better functional and metabolic recovery in association with better preservation of ultrastructure through improving energy production-utilization balance in early reperfusion period. And rapid warming in the reperfusion period may deteriorate or delay the myocardial recovery from ischemic isult. PMID- 2584772 TI - [Interest of percutaneous transvenous mitral commissurotomy in the management of rheumatic mitral stenosis]. AB - During from April 1987 to October 1988, 13 cases of mitral stenosis (MS) were treated with percutaneous transvenous mitral commissurotomy (PTMC) among 24 cases of MS. The indications of PTMC were determined by surgeons in 4 cases with several reasons described as follows: 1. Patient, having been treated with closed mitral commissurotomy, who refused to be operated with open heart technique. 2. Patient associated with early gastric cancer. 3. Patient associated with severe hyperthyroidism and cardiac cachexia. 4. Patients suffering from acute renal failure following left heart failure due to association of aortic stenosis. Other 9 cases were determined by cardiologist because of the inherent benefit of PTMC being less invasive. After PTMC, the symptomatic improvement, assessed by means of NYHA classification, were observed in 11 cases out of 13. Hemodynamic data such as mitral valvular area, mitral valve gradient and cardiac index showed marked improvement without any inducing of significant mitral regurgitation. The authors thought with these results as follows: 1. The effect of PTMC may be appreciable for mild or moderate stenotic lesion of mitral orifice, however, severely affected valves should be treated by open heart techniques in order to perform radical procedures. Otherwise, significant MR may occur by overloading of balloon size beyond some extent. 2. On account of the appearance of PTMC, the indicational determination for the treatment of MS will be more controvertial than now. PMID- 2584773 TI - [Treatment of prosthetic valve endocarditis--analysis of eleven cases]. AB - A retrospective examination was made of eleven patients that developed prosthetic valve endocarditis (PVE) during the period from January 1960 to December 1987. Infection occurred in one patient within 60 days after surgery and in 10 thereafter. Causative organism was found in 6 patients. As organism, Staphylococcus species were noted in 4 patients and Peptstreptococcus was noted in one patient and Aspergyllus was noted in one patient. Three of eleven patients received medical treatment only and the other 8 patients were received surgical treatment. Mortality rate was 67% in medical group and 29% in surgical group. Two patients with medical treatment died of cerebral infarction about 40 days after the onset of PVE. In surgical group one patient died of uncontrollable Aspergillus infection and the other one died of dyspnea. No survivors who was treated surgically have developed reinfection or relapse of infection but four of them developed perivalvular leakage and needed reoperation. Absolute removal and closure of the valve ring abscess and reconstruction of defect should be considered for those needed surgical treatment to prevent reinfection and relapse developing. PMID- 2584774 TI - [Influence of cardiopulmonary bypass on plasma lipid peroxides]. AB - In 22 patients who underwent cardiac surgery with cardiopulmonary bypass (CPB), we studied the influence of CPB on the level of lipid peroxides (LPO) in plasma by means of measuring the time course of plasma LPO level during and after CPB. We expressed LPO level, which was measured by thiobarbituric acid reaction, as the level of malondialdehyde. In our preliminary study, it was found necessary to correct the plasma LPO level diluted by priming fluids of CPB machine and the concentration of plasma protein was fitted for its correction. In the following study, we used the plasma LPO level corrected by the concentration of plasma protein. LPO were significantly decreased since the initiation of CPB (1.669 +/- 0.208 versus pre-CPB 1.785 +/- 0.158 log nmol MDA/gm protein, p less than 0.05) to the post CPB 30 minutes, except around 60 minutes after initiation of CPB (1.735 +/- 0.242 log nmol MDA/gm protein, p greater than 0.05). As the initial change (the values at 30 minutes after CPB initiation) may express the effect of CPB directly in this time course of LPO, we analyzed the initial change on different background factors. By ordinary analysis of the initial change, as to the effect of type of disease (congenital and acquired), LPO were decreased in the acquired group (1.617 +/- 0.197 versus pre-CPB 1.779 +/- 0.163 log nmol MDA/gm protein, p less than 0.05). At that time the acquired group was significantly different from the congenital group (1.799 +/- 0.191 versus pre-CPB 1.800 +/- 0.157 log nmol MDA/gm protein, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584775 TI - [Experimental studies of the esophageal prosthesis with a polyvinyl alcohol hydrogel]. AB - Though various prosthetic materials have been experimented with for use as an artificial esophagus in the past, the two main problems that have prevented successful clinical implantation of such a prosthesis were anastomotic leakage and stricture formation of the artificial esophagus. The purpose of this study is to evaluate a high water content polyvinyl alcohol hydrogel (PVA-H) for use as the esophageal prosthesis. In 10 adult mongrel dogs, the defect after resection of the intrathoracic esophagus was bridged with a PVA-H esophageal prosthesis, 5.5 cm in length and 15 mm in internal diameter with two Tefron rings, installed 2 cm from each end. The esophageal prostheses, including the anastomotic lines, were enveloped by Dacron mesh after implantation. After implantation, the prostheses were examined endoscopically and fluoroscopically. The dogs, which were sacrificed or had died, were evaluated macro- and microscopically. Among the six dogs underwent operation, one is still living 900 days after implantation. The other two dogs were sacrificed on 165 and 162 days after implantation. The remaining three dogs died of postoperative complications ranging from 25 to 81 days after implantation. The causes of death were the respiratory insufficiency after endoscopical examination, abscess formation around the prosthesis and pyothorax. Up to 2 months after implantation the esophageal prostheses were fixed to the host esophagus without stenosis. However, the prostheses were gradually dislodged due to constricture depending on the growing granulation at the proximal anastomosis. When the surviving dog was examined on the 376th day after the operation, the esophageal prosthesis fell off entirely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584776 TI - [Effects of the site of distal anastomosis on the branch flow of coronary arteries in an A-C bypass grafting]. AB - Hemodynamics of coronary branch with retrograde blood flow of the host artery was examined in seven mongrel dogs, when the distal side of the graft was anastomosed at distal site to branching point in A-C bypass grafting. A Y-shaped tube was interposed to reconstruct coronary blood flow between the right carotid artery and the left anterior descending coronary artery (LAD), its one arm of Y was connected to proximal site of the branching point of the first diagonal artery (proximal anastomosis), and the other arm was connected to distal site of the branching point (distal anastomosis). After the LAD was ligated just distal to the bifurcation from the left main coronary artery, each arm was clamped in turn, and blood flow of the first diagonal branch was evaluated. Heart rate, left ventricular pressure and cardiac output (cardiac function), and blood pressure, flow and resistance of the interposed tube (bypass function) were not changed significantly in each arm clamped. The diagonal branch flow decreased from 11.2 +/- 2.7 ml/min (mean +/- S.D.) in proximal anastomosis to 10.3 +/- 3.1 ml/min in distal anastomosis with significant difference (P less than 0.05). The diagonal branch/bypass graft flow ratio decreased from 0.422 +/- 0.159 in proximal anastomosis to 0.395 +/- 0.160 in distal anastomosis with significant difference (p less than 0.05). The blood flow in systolic phase of the diagonal branch tended to increase in distal anastomosis as compared with proximal anastomosis. However, diastolic flow of the branch significantly decreased from 8.3 +/- 2.1 ml/min in proximal anastomosis to 7.1 +/- 2.2 ml/min in distal anastomosis (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584777 TI - [Complication related to operative procedure in lung cancer and mediastinal malignancy--report of 6 cases]. AB - Of the patients who underwent surgical treatment for the respiratory system at our hospital over the past 9 years, 6 were postoperatively complicated with chylothorax, 1 with liquorrhea and the other one with paraplegia. Chylothorax occurred after mediastinal lymph node dissection which was carried out for the treatment of malignant tumors. In five cases, it occurred on the left side, and in the sixth case, it occurred on the right side. In 2 patients who received conservative treatment, there was no reduction in chyle outflow, and they died of cerebral infarction and sepsis. The other 4 cases were surgically treated. In 3 of them, the impaired site of the thoracic duct was confirmed by administration of Sudan III before surgery. We confirmed that early reoperation for the chylothorax after lung resection should be performed. Liquorrhea occurred from the 5th costvertebral joint which had been directly infiltrated by lung carcinoma. Fortunately, the postoperative course was uneventful, though the patient complained of dizziness and headache until 14 postoperative days. The case of paraplegia was caused by oxydized cellulose cotton that entered the epidural space via the intervertebral foramen. It was used for hemostasis in the 5th costvertebral joint. This case indicates that oxydized cellulose cotton, which swells when it absorbs water, should be carefully used for hemostasis around the nerves. PMID- 2584778 TI - [Improvement of extracorporeal circulation on the basis of anaphylatoxin levels, with special reference to oxygenation mechanisms and plasma denaturation by oxygen bubbling]. AB - Complement activation was evaluated in 76 patients undergoing cardiopulmonary bypass (CPB) with particular reference to anaphylatoxin levels. These patients were divided into membrane (MOG) and bubble oxygenator groups (BOG). The influence of primed homologous to circulating autologous blood volume (H/A) ratio was also examined. Each group was further divided into two subgroups: one was primed with homologous whole blood, and the other with fresh homologous concentrated red cells (CRC) and human albumin. C4a slowly increased during CPB in both groups, maintaining slightly higher levels in the BOG than in the MOG. A marked initial rise was observed in the BOG with high H/A ratios. C3a increased more steeply in the BOG than in the MOG. C5a levels in the BOG were higher than in the MOG. The influence of the H/A ratio was milder in the MOG than in the BOG. In the BOG, the anaphylatoxin levels in the group primed with CRC and human albumin were slightly lower than in the group primed with whole blood. However, anaphylatoxin levels rose most steeply in cyanotic patients even though they were perfused with a membrane oxygenator. In experimental studies using 20 monkeys (Macaca fascicularis), continuous intraaortic infusion with O2 bubbled autologous blood increased C4a and C3a levels, while autologous blood extracorporeally contacted with nylon increased C3a levels alone. C4a and C3a levels were unchanged by infusion with O2 microbubbles. In vitro studies revealed that human immunoglobulin denatured by O2 bubbling produced C4a, C3a, and C5a in a dose dependent manner, although human albumin treated identically as human immunoglobulin did not produce them.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584779 TI - [Clinical study of the effect to myocardial protection with crystalloid cardioplegic solution during open heart surgery in infants under age 3 months]. AB - We investigated the effect to myocardial protection with crystalloid cardioplegic solution (Kurume solution I (S-I)) during open heart surgery in 21 infants less than 3 months old. The mortality was 28.6% (6 cases) including 2 patients having peroperative severe acidosis or shock. It was suggested that about half of them died of inadequate myocardial preservation. Comparing factors in the deaths with the survivors, there were significant differences between them in extracorporeal circulation time (ECCT) (196.7 +/- 50.1 min versus 133.2 +/- 45.8 min, p less than 0.01) and aortic-cross clamping time (ACCT) (120.0 +/- 45.8 min versus 78.3 +/- 30.5 min, p less than 0.05). In survivors, 86.7% of them required the effective dose (more than 6 micrograms/kg/min) of catecholamine and 33.3% presented low cardiac output syndrome (with the dose of more than 10 micrograms/kg/min and more than for 48 hours). The incidence of LOS was related to ECCT and ACCT. Thus it seemed that infant was more susceptible than older patient to the effects of ECC and the operation was carried out safely with ECCT less than 150 minutes and ACCT under age 3 months, it is necessary to use the cardioplegic solution fitting immature myocardium and to design operative technique and assist device for open heart surgery to shorten ECCT and ACCT. PMID- 2584780 TI - [Primary lung cancer of the right middle lobe]. AB - During the period from 1973 to 1986, 230 patients with lung cancer were operated on at our Surgical Clinic of Kagoshima University Hospital. There were fourteen patients (6.1%) with lung cancer in the right middle lobe. There were 13 male and 1 female patients. The histological types were adenocarcinoma (10), squamous cell carcinoma (4). Five-year survival rate of 14 patients was 34.9%. Statistically, it was similar to that of the patients with lung cancer in the other lobes. As concerns with the histological type of lung cancer in the right middle lobe, the case of squamous cell carcinoma revealed poorer prognosis than those of adenocarcinoma, because there were many cases of advanced cancer in the former case. PMID- 2584782 TI - [A case report of ventricular septal defect accompanied by winded and elongated malformation of the aortic arch]. AB - A three-year-old boy, surgically treated for a ventricular septal defect, had a winded and elongated aortic arch between the left common carotid artery and the left subclavian artery. Angiography revealed that the arch was positioned more caudalward than normally, and that it was in contact with the left pulmonary artery at a point near the central portion of the arch (i.e., near the position of the ductus arteriosus). The embryological cause of this malformation was speculated. It seemed unlikely that malformations was caused by involution, abnormal growth, etc., of the components of the great vessels in the coursed of embryonic development, but rather to have been caused by an abnormal elongation of the artery at the fourth arch and of the ventral artery between the 6th and 7th intersegmental artery, which had occurred after normal embryonic development. Under extracorporeal circulation, where blood was returned to the patient via the femoral artery, the patient underwent open heart surgery to close the ventricular septal defect. Pressure monitoring during the operation revealed no pressure loss in the winded and elongated portion of the artery; hence, the malformation seemed to cause no hemodynamic problems at present. Considering that the patient is only three years old and that the aorta will continue to grow, we have decided to refrain from any surgical treatment of the winded and alongated part of the aorta for the time being. However, the patient might develop aortic aneurysm in the future because of the relative coactation of the aorta and the insufficient mechanical strength of the winded and elongated area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584781 TI - [Surgical treatment of rheumatic tricuspid valve disease]. AB - The rheumatic tricuspid valve is relatively rare in this country. We report the study on surgical treatment of 27 patients with rheumatic tricuspid valve. Surgical procedure on 7 cases out of them was tricuspid valve replacement (TVR) with bioprosthesis and tricuspid valvuloplasty (TVP) was performed in the remaining 20 cases. There were two operative deaths in TVR group, however, there were no major complications, such as thrombosed valve, the valve dysfunction or prosthetic valve endocarditis in the remaining five cases after the operation. The method of TVP in twenty cases consisted of two Kay's TAPs, six tricuspid commissurotomies (OTC), ten OTC with Key's TAPs and two OTC with DeVega's TAPs. Doppler cardiography (DCG) revealed residual tricuspid regurgitation (TR) more than 3/4 degrees in 7 cases of TVP group immediately after operation. Moreover, the increment of residual TR was seen in 7 cases during the following period and TVR was performed in 3 cases out of these 7 cases. In conclusion, it is suggested that TVR may be preferred to TVP for the rheumatic tricuspid valve because of severe residual TR in many cases of TVP group. PMID- 2584783 TI - [Long-term survival with Hufnagel ball valve--a case report]. AB - Authors report a 61-year-old female with an aortic aneurysm at the distal end of the Hufnagel ball valve which was implanted surgically for the treatment of aortic insufficiency 23 years previously. The Hufnagel ball valve has been working well for the past 23 years, but the aneurysm was found enlarging in size, therefore the replacement of aneurysm with a 20 mm dacron graft was performed following removal of the well-working Hufnagel ball valve. There were 151 cases with Hufnagel ball valve implantation in the literature and at least 7 cases of them were reported in Japan. Among them, the majority survived only several years after surgery and the cases with long-term survival were very few in number. Our case is unique, because the valve in this case has worked well for 23 years. PMID- 2584784 TI - [Postpneumonectomy esophagopleural fistula--successful one-stage repair with omental flap and thoracoplasty]. AB - A 69 year-old man, who had undergone left pneumonectomy for squamous cell carcinoma of the lung 21 months ago, was admitted with a high temperature and chest pain. A diagnosis of empyema was made, and a chest tube was inserted for drainage. Bronchopleural fistula was not noted. Noticing that food was leaking through the drainage tube, a diagnosis of esophagopleural fistula was made radiologically. Surgery was done in October, 1987, after irrigating an empyema space for two months. The fistula was approximately 4 cm below the carina, and it was closed directly. The omentum was sutured around the closed site to reinforce and obliterate the empyema space. Furthermore, additional thoracoplasty was done because the cavity was too large to close only with the omentum. The postoperative course was uneventful. He was able to eat specially prepared foods within 4 weeks, and was discharged on the 60th day after the operation. This patient could possibly be the first case who had undergone an omental flap for the closure of a postpneumonectomy esophagopleural fistula. PMID- 2584785 TI - [Coronary artery bypass grafting in a patient with Sjogren's syndrome and other autoimmune diseases]. AB - Coronary arterial involvement in collagen disease is a very rare complication. Particularly in Sjogren's syndrome is there no report of coronary artery bypass grafting (CABG). We report a 68-year-old woman with various autoimmune diseases who underwent successful CABG for unstable angina pectoris. She had a history of Sjogren's syndrome, hypothyroidism, thrombocytopenia and lupoid hepatitis, and had been on the regimens of prednisolone and levothyroxine sodium during the last 4 years. Two months prior to admission when the doses of these drugs were increased, she began to complain of angina on mild exertion and occasionally even at rest. Selective coronary angiograms revealed 75% stenosis at Seg. 2 and 99% stenosis at Seg. 6. Based on these findings and severity of the angina, saphenous vein CABG to the posterior descending and the left anterior descending branches was performed. Despite the associated autoimmune diseases, the patient's postoperative course was uneventful and she is now doing well with no attack of angina, 12 months following the operation. PMID- 2584786 TI - [Surgical treatment of acute pulmonary embolism--report of two cases]. AB - Two surgical cases of acute pulmonary embolism with severe cardiocirculatory impairment were reported. In the first case, emergent open pulmonary embolectomy with cardiopulmonary bypass was not effective, and multiple and organized emboli were indicative. In the second case, complete pulmonary thromboembolectomy was accomplished under extracorporeal circulation with remarkable hemodynamic improvement. It was suggested that urgent pulmonary angiography was necessary for definitive diagnosis and medical treatment, and that indications for pulmonary embolectomy included all patients with massive emboli in the main branches of the pulmonary artery. Monitoring of pulmonary arterial pressure was important to assess the effect of thrombolytic therapy, and the system of emergent cardiopulmonary bypass was required for immediate and effective cardiopulmonary resuscitation. PMID- 2584787 TI - [A successfully operated case of isolated tricuspid insufficiency due to traumatic laceration of anterior leaflet of tricuspid valve]. AB - A case of isolated traumatic tricuspid insufficiency is presented. The patient was a 26-year-old designer with chief complaints of palpitation and dyspnea on exertion, who had the traffic accident three years and four months ago. The cardiac catheterization and two-dimensional echocardiography showed isolated insufficiency, and revealed that the basic damage was laceration of anterior leaflet of tricuspid valve itself. Tricuspid valve was replaced with SJM M-31 valve. His postoperative course was satisfactory. Until present to our knowledge, 13 cases of traumatic tricuspid insufficiency have been reported in Japan including our case. In three instances the papillary muscles ruptured. In nine patients the chordae tendineae were torn and in this case, there was primary laceration of anterior leaflet. PMID- 2584788 TI - [A case report of hypertrophic obstructive cardiomyopathy after the correction of atrioventricular septal defect]. AB - A 47-year-old woman who had closure of an atrioventricular septal defect and repair of mitral cleft developed severe dyspnea on effort 6 years after surgery. An echocardiography showed asymmetric left ventricular hypertrophy and a left cardiac catheterization revealed marked intraventricular pressure gradient and moderately severe mitral regurgitation. The patient underwent mitral valve replacement through transseptal approach during empty beating heart. Symptomatic relief was obtained and marked reduction of intraventricular systolic pressure gradient was noted in postoperative cardiac catheterization about 40 days after the operation. Mitral valve replacement should be considered for the treatment of hypertrophic obstructive cardiomyopathy in severe cases with associated morphological abnormality of mitral leaflet or severe mitral regurgitation. PMID- 2584789 TI - [A successful arterial switch operation for the transportation of the great arteries with posterior aorta--with special reference to its anatomical features and possibility of the indication of the Jatene procedure]. AB - A five months old infant with the transposition of the great arteries with posterior aorta undergoing arterial switch operation is reported. A pre-operative diagnosis of the transposition of the great arteries with posterior aorta, subarterial ventricular septal defect, anterior pulmonary artery, bilateral conus and fibrous continuity between aortic and mitral valve was made. This diagnosis was confirmed by the open heart surgery. The ventricular septal defect was subaortic from the transected aortic aspect, and the infundibular and trabecular septum was aligned. For these reasons, this subarterial ventricular septal defect was easily closed transaortically. The right coronary artery arose from the left sinus and the left coronary artery from the posterior sinus, so the coronary arterial pattern of this patient was a Shaher type 9. And in addition, another small ostium located in the left sinus gave rise to an additional small branch. Translocation of the coronary arteries was performed. The new pulmonary trunk was reconstructed to the right pulmonary artery so as not to compress the coronary artery and distort the great arteries. This patient was restudied three months after the repair. The right to left ventricular systolic pressure ratio was 0.42 and no pressure gradient was present between the right ventricle and the right pulmonary artery. But a moderate aortic regurgitation was detected. This was caused by deformity of the aortic sinus of valsalva. Only 28 patients with the transposition of the great arteries with posterior aorta were reported in the literature, but there were no reports on the successful surgical treatment for its rare anomaly, to our knowledge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584790 TI - [A case of giant mediastinal cystic lymphangioma]. AB - A 13 year-old boy was admitted because of anterior chest pain, fever up and exertional dyspnea. Chest X-ray film showed a large mass shadow on the middle and lower lung field with positive silhouette sign. Under the ultra-sonic tomogram the mass showed cystic pattern with septum. The bloody fluid collected by puncture suggested hemorrhage into the cyst. Chest CT scan revealed a well defined cystic mass in the left thoracic space. The mass reached to the right thoracic space through behind the Inferior Vena Cava (IVC). At operation, although the tumor adjoined heart, esophagus, diaphragma and IVC, it was removed completely. Pathological diagnosis was cystic lymphangioma. PMID- 2584791 TI - Lung cancer: reconstruction of the trachea and bronchus. PMID- 2584792 TI - Development of surgery of the oesophagus in Europe. PMID- 2584794 TI - Trends in coronary artery reoperation. PMID- 2584793 TI - Surgery for complete form of atrioventricular canal defects with or without cono truncal anomalies. PMID- 2584796 TI - Perioperative care in infant heart transplantation. PMID- 2584795 TI - RATG: 10 year experience in cardiac transplantation. PMID- 2584797 TI - Myocardial biopsy in heart and heart-lung transplantation. PMID- 2584798 TI - Acute and chronic rejection of the lung following heart and lung transplantation. PMID- 2584799 TI - The use of surgical glue without replacement in the treatment of type A aortic dissection. PMID- 2584800 TI - Surgical treatment for mitral regurgitation due to coronary artery disease. PMID- 2584801 TI - Neonatal repair of Fallot's tetralogy with and without pulmonary atresia. PMID- 2584802 TI - Rapid two-stage arterial switch operation for TGA. PMID- 2584804 TI - [Interleukin 2 receptor]. PMID- 2584803 TI - Dynamic cardiomyoplasty to enhance cardiac performance. PMID- 2584805 TI - [Biological activities of algal polysaccharides]. PMID- 2584806 TI - [Clinical studies of IgA nephropathy during pregnancy]. AB - We have obtained some new findings from the observation and management of 15 pregnancies and deliveries, all complicated with IgA nephropathy, which was diagnosed by open renal biopsy before each pregnancy. The classification of IgA nephropathy was from Grade I to Grade IV according to Nomoto et al. Clinical and pathological changes during each pregnancy were observed in the appearance and degree of edema, proteinuria and hypertension. The criteria were based on the classification of toxemia of pregnancy of the Committee for Toxemia of Pregnancy. Japan Society of Obstetrics and Gynecology. We referred to laboratory data such as complete blood counts, coagulation tests, blood chemistry tests, urinalysis and renal function tests. We also referred to Amagasaki's criteria which indicate whether the pregnancy and delivery will be normal or not. Three cases with Grade I IgA nephropathy all had normal courses. Nine cases with Grade II satisfied the criteria of Amagasaki for normal delivery, but during the third trimester, proteinuria was recognized in seven cases, edema in one case and hypertension in two cases. Three cases with Grade III were all met the criteria for abnormal pregnancy and delivery. Only one case showed proteinuria from the first trimester, but she had no obstetrical complications or deterioration of renal function during her course. There were 12 vaginal deliveries and three Cesarian sections. All infants were in good condition except for one intrauterine fetal death. In view of the above results, we concluded that patients with Grade II IgA nephropathy could not continue their pregnancies safety. However, some of the patients with Grade III had successful deliveries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584807 TI - [Clinical spectrum and congenital anomalies in trisomy 18]. AB - Ultrasound sonography has become a major diagnostic tool in the detection of fetal trisomy 18. And, because understanding fetal trisomy 18 is important for us, we examined the variegated presentations of trisomy 18. Clinical observation of 16 cases and autopsy findings in 14 cases of 18 trisomy are presented. These patients were seen during the seven-year period 1981-1988. All patients died in the first 3 months of life. The mean maternal age was 31.8 years and other clinical observation coincided well with those of other reports well recognized. In 15 cases, typical features of 18 trisomy (intrauterine growth retardation, trisomy face, hand and foot deformities) were seen. However, one case presented an atypical phenotype. Holoprosencephaly was superimposed, and this combination is believed to be unique. Another abnormality of the central nervous system was cerebellar hypoplasia in 50% of the cases and this incidence was much higher than in Smith's textbook (less than 10%). And in this paper we also reported a rare anomaly of the coronary artery and described first an abnormality of aortic arch and calcification of the placental vein in this paper. Findings in the present study were compared to the literature. PMID- 2584808 TI - [Role of progesterone in the ovulatory process of PMSG/hCG treated immature female rats]. AB - To determine exactly when progesterone (P) acts as a most important mediator in the ovulatory process, a dose of 10mg/kg of RU486, an antiprogesterone, was administered to PMSG/hCG treated immature female rats (22 days old) at 0 (RU0 groups), 2 (RU2 group), 4,6,8 or 10 hours after an hCG injection, respectively. In the RU0 groups, the ovulatory effect of P was investigated at 0.2 (P2 group), 4 (P4 group), 6 or 8 hours after the hCG injection. Ovulation rates were calculated 24 hours after the hCG injections. Serum P and estradiol (E2) concentrations in the RU0 groups, the P2 group and the control rats (C group), were determined. The results were as follows. 1) The numbers of ova in the RU0, RU2 and RU4 group rats were significantly (p less than 0.01, p less than 0.01 and p less than 0.01) lower than that in the C group rats. 2) In the P2 and P4 groups, the numbers of ova were significantly (p less than 0.01 and p less than 0.01) increased compared with the RU0 group and returned to the control range. 3) In the RU0 group, the serum P and E2 concentrations within 8 hours after an hCG injection did not show any significant differences compared with the C group. In contrast, in the P2 group, the P concentrations at 4 and 6 hours after hCG increased significantly (p less than 0.01 and p less than 0.01) compared to the corresponding RU0 group. These results clarified an indispensable role of P in the ovulatory process within 6 hours after an hCG injection. PMID- 2584810 TI - [N-myc amplification and neuron-specific enolase production of ovarian immature teratoma]. PMID- 2584809 TI - [CDDP-ACR treatment in patients with recurrent ovarian cancer with prior chemotherapy containing CDDP--a preliminary study of a 14-day continuous infusion of CDDP with ACR]. AB - Six patients with recurrent ovarian cancer who had prior chemotherapy were studied for the clinical efficacy of CDDP-ACR treatment. Five out of the 6 had received CDDP a total doses of 1,320, 780, 750, 475, and 340 mg. CDDP-ACR therapy consisted of continuous infusion of CDDP at a daily dose of 10 mg/m2 over 14 days (total CDDP doses; 140 mg/m2) and of intermittent infusion of ACR (aclarubicin) at a dose of 20 mg/body every other day (total ACR doses: 140 mg). There were one CR and five PR and a response rate up to 100% was noted. Toxicity was manifested in slight nausea or vomiting, but there was no nephrotoxicity. However bone marrow was severe. Thrombocytopenia less than 50,000/mcl in 4 pts (67%) and leukopenia less than 1,000 mcl in 3 pts (50%). The mean filterable platinum exposure measured by area under the concentration-time curve (AUC) was as high as 19.7 +/- 6/0 mg.hr/ml. In conclusion the bone marrow toxicity in this regimen was severe, but the therapeutic efficacy was promising. Further studies on the appropriate infusion time and the minimum effective dose of CDDP are needed. PMID- 2584811 TI - [Hemolytic disease of the newborn due to anti-Kidd Jka sensitization during pregnancy]. PMID- 2584812 TI - [Ultrastructural localization of prolactin in the cytoplasmic processes of the cumulus granulosa cells and the microvilli of the oocyte in the rat ovary]. AB - The cytoplasmic processes of the cumulus granulosa cells are known to play an important role in connecting these cells with the oocyte, and in supplying nutrition and some to the oocyte for its growth and maturation. And it is also found that the follicular fluid contains prolactin, and that prolactin is present in the cytoplasm of the cumulus granulosa cells and the oocyte when studied by the light microscopic histochemical staining procedure. In this study, we used the protein A-colloidal gold method for transmission electron microscopic observation of the localization of prolactin in the cumulus granulosa cells and the oocyte in the rat ovary. We proved that prolactin is present in the cytoplasmic processes of the cumulus granulosa cells and in the microvilli of the oocyte. Therefore, it is suggested that prolactin is transported from the follicular fluid through the cytoplasmic processes of the cumulus granulosa cells, and that prolactin is absorbed into the oocyte from its microvilli. PMID- 2584813 TI - [The mechanism of resistance and its circumvention of cisplatin-resistant human ovarian cancer cells]. AB - In this study, we attempted to elucidate the mechanisms of cisplatin resistance and circumvent the resistance with calmodulin antagonists using a cisplatin resistant human ovarian cancer cell line (KFr). It was assumed that the cisplatin resistance resulted from impairment of cisplatin transport systems. In particular, we considered that a reduced cisplatin transport function caused by some amino acids had an effect on the resistance mechanism. Reduced uptake of cisplatin as well as cisplatin analogues to KFr cells was observed. Four cisplatin analogues used in this study had cross-resistance to cisplatin. However, the concentration of drugs incorporated into cells was not always correlated with the degree of resistance. Therefore, it is possible that, in addition to the reduced influx function, an other mechanism is involved in the resistance. Combined treatment with cisplatin and calmodulin antagonists significantly increased the uptake of cisplatin by KFr cells and maintained the cellular level. Thus, a combination therapy of cisplatin and calmodulin antagonists seemed to be of clinical use. PMID- 2584814 TI - [Establishment and characterization of ovarian pure dysgerminoma cell line secreting human chorionic gonadotropin]. AB - A cell line, designated KURATOU, was established from a human chorionic gonadotropin (hCG)-secreting pure dysgerminoma of the ovary. The cell line comprised small cells resembling original tumor cells and large ones possessing one or a few nuclei. Population doubling time was calculated to be about 10 days. An enzyme immunoassay study of hCG in media showed that the cells produced 7-9 x 10(-6) IU/cell of hCG. Immunocytochemical studies revealed hCG in almost all of the cultured cells. The chromosomal number was distributed in triploid and the modal chromosomal number was 69. Some cells contained HLA-ABC antigens, but none contained HLA-DR antigens. The cell line was transplanted into a nude mouse and produced a tumor resembling the original tumor but with no other tumor elements. PMID- 2584815 TI - [Analysis of trophoblast subpopulations on touch smears of chorionic villi during normal pregnancy]. AB - Trophoblasts of normal human pregnancy are classified into syncytiotrophoblasts (STs), cytotrophoblasts (CTs) and intermediate trophoblasts (ITs) which exist in cell columns and so forth. We analyzed the trophoblast subpopulations which appear on touch smears of chorionic villi morphologically and immunohistochemically, using the uterine contents of 37 cases of induced abortion. Troma 1, a rat monoclonal antibody, was utilized as a trophoblast marker and a mouse monoclonal antibody to HLA-A,B,C was employed to discriminate ITs from CTs. The results were as follows: 1. Two sorts of cells were positive for Troma 1 and therefore were considered to be trophoblastic: Multinuclear cells of various sizes and relatively large mononuclear cells. 2. Multinuclear trophoblasts were thought to be STs because of their characteristic cytomorphology and negative reaction for HLA-A,B,C. 3. The lower the gestational age was, the more ITs were observed. 4. The cellular and nuclear size of ITs varied and their chromatin was coarsely granular with aggregates. In addition one or more marked nucleoli were noted. Consequently it would be important to take care not to misdiagnose ITs as trophoblasts of a malignant nature. PMID- 2584816 TI - [Study on intracardiac blood flow with color flow mapping in human fetus--the reverse flow at tricuspid valve in human fetus during labor]. AB - This study was performed to determine the relation among the reverse flow signal of tricuspid valve, fetal heart rate pattern and uterine contraction. The blood flow signal through the tricuspid valve was continuously recorded with color flow mapping and direct fetal electrocardiogram as well as uterine contraction in 17 human fetuses during labor. Gestational ages ranged from 36 to 41 weeks. No fetus had a congenital heart anomaly. The detection rate of the reverse flow signal at the tricuspid valve was 100% in variable deceleration, 33% in late deceleration, 5% in normocardia and none in early deceleration. In investigation of the time relation between the reverse flow signal and variable deceleration, the reverse flow signal started after the onset of the recovery phase of deceleration. The tricuspid reverse flow, which was observed in variable deceleration, was caused by an increase in the venous return when cord compression disappeared at the onset of the recovery phase of variable deceleration. PMID- 2584817 TI - [Hemorheological studies on platelet counts and size in normal pregnancy and pregnancies with preeclampsia and intrauterine growth retardation]. AB - It has been reported that preeclampsia and pregnancy resulting in intrauterine growth retardation (IUGR) are associated with high hematocrits. The relations between hematocrits (Ht) and platelet volumes in normal and abnormal pregnancies were investigated to clarify a hemorheological effect on formation of microthrombus. 1) In normal pregnancy, Ht was decreased from 12-19 weeks gestation and reached its lowest level at 28-31 weeks gestation. The mean platelet volume (MPV) was decreased from 20 to 31 weeks gestation but markedly increased from 38 to 41 weeks gestation. The platelet count (Pl) remained unchanged during pregnancy. 2) In severe type of preeclampsia, at 28-37 weeks gestation Ht and MPV were markedly increased and Pl was markedly decreased at 38 41 weeks gestation as compared with normal pregnancies. 3) Mothers who delivered IUGR had a much higher level of Ht at 28-35 weeks gestation and MPV level from 38 weeks gestation than in normal mothers. As the volume of young platelets is large, increased MPV is suggestive of the occurrence of platelet consumption. From these results, it was suggested that microcirculatory disturbances such as higher blood viscosity due to hemoconcentration and microthrombus formation were related to the onset of preeclampsia or IUGR. PMID- 2584818 TI - [Cytogenetic studies in couples with repeated spontaneous abortions]. AB - Chromosome studies were carried out on both partners of 509 couples with a history of two or more spontaneous abortions. 1) Twenty-six individuals (2.6%) were carriers of a major chromosome abnormality. This incidence is at least six to seven times higher than that in the general adult population. 2) Of these, 10 were reciprocal translocations, 10 robertsonian translocations and 6 numerical aberrations of gonosomes. None of the carriers showed abnormal phenotypes. 3) Chromosome aberrations were more frequent in the women than in their husbands. There were 19 abnormalities in females and 7 in males. 4) The use of banding techniques in chromosome analysis improves the detection of balanced reciprocal translocations. 5) Prenatal diagnosis was performed in 5 subsequent pregnancies of 4 balanced translocation carriers. The fetal karyotypes were 2 normal and 3 balanced translocations. It would seem reasonable to recommend chromosome analysis for couples with repeated spontaneous abortions. PMID- 2584819 TI - [Fetal screening of congenital heart disease]. AB - Echocardiograms of two hundred and ninety normal fetuses at 18-39 weeks of gestation were studied with a real-time linear scanner (3.5 MHz). Aortic valvular diameter, pulmonary valvular diameter, mitral valvular diameter, tricuspid valvular diameter and total cardiac dimension were measured. These parameters increased with fetal growth. The ratios of pulmonary to aortic valvular diameter and of tricuspid to mitral valvular diameter were more than 1, suggesting right ventricular dominance in the fetal hearts. The cardio-thoracic ratio was about 50% in this period. The four-chamber view, left ventricular long-axis view, ventricular short-axis view, short-axis view of the great arteries, the view of the aortic arch and the view of the inferior and superior vena cava were also recorded. These six views could be obtained in 9.8% of all subjects at the same time. Detection rates for these views were the greatest in pregnancy at 22-33 (especially 28-29) weeks of gestation. The ventricular short-axis view and short axis view of the great arteries were easily detected in the dorsoposterior position, whereas the view of the aortic arch was obtained in the dorsoanterior position. It was concluded that fetal echocardiography needed to be performed at least twice, at 22-23 and 28-29 weeks of gestation, and this would be useful in diagnosing some congenital heart diseases. PMID- 2584820 TI - [Experimental model of respiratory distress syndrome by lung lavage with fluorocarbon]. AB - The purpose of this study was to determine how much alveolar surfactant is washed out by lung lavage with fluorocarbon and also to find out whether or not instillation of artificial surfactant can restore pulmonary function after lung lavage in rats. The lung lavage was performed manually, administering a tidal volume 5 mg (2 mg/100g body weight) of fluorocarbon for about eight seconds. This process was repeated more than 40 times. In the study group, 4 ml/kg (120 mg/kg) of artificial surfactant was instilled into the trachea, and the same amount of normal saline was instilled in the control group. The amount of phospholipids extracted in lung lavage was 16.6 +/- 3.6 mg/kg body weight in the control group and 18.9 +/- 3.7 mg/kg body weight in the experimental group. Immediately after instillation of the surfactant, arterial oxygen pressure increased from 84 +/- 17 mmHg to 195.1 +/- 26.7 mmHg, and remained high, at about 170-260 mmHg. In contrast the physiological saline treated group did not show any change. We conclude that lung lavage with fluorocarbon is an adequate ideal experimental model of respiratory distress syndrome and suggests that combination of artificial surfactant treatment after lung lavage with fluorocarbon might be a new pulmonary washing method for severe lung disease. PMID- 2584821 TI - [Changes in bone mineral content and bone metabolism related to menopause]. AB - Although the phenomenon of postmenopausal osteoporosis has attracted attention, there have been no parameter-matched studies of pre- and postmenopausal difference in metacarpal bone mineral status and bone metabolism. Therefore the authors compared metacarpal bone loss in a group of 41 postmenopausal volunteers (average postmenopausal duration: 39.3 months) and 28 age- and body size-matched controls (age 50-54), using the MD method. Perimenopausal changes in bone metabolism were also examined in these groups. The result revealed that the reduction in the metacarpal bone mineral status due to menopause occurs mainly in the bone mineral density such as GSmin and sigma GS/D. The reduction rate was the highest for the index of GSmin, corresponding to 5.1% per year. Serum levels of Alp and osteocalcin were significantly higher and the U-Ca/cr ratio tended to be higher in the postmenopausal subjects than in controls. The serum levels of calcium regulating hormones such as PTH and calcitonin in these two groups did not differ significantly. However the estrone and the estradiol levels, were significantly lower in postmenopausal subjects. Significant correlations were found between Alp and the postmenopausal period (r = 0.4684), and between the U Hpr/cr ratio and postmenopausal period (r = -0.5332). It therefore appeared that estradiol is mainly related to postmenopausal bone metabolism causing insufficient suppression of bone resorption. However, calcium regulating hormones appeared to be not directly related to the postmenopausal bone loss mechanism. Bone turnover decreased with the postmenopausal period. PMID- 2584822 TI - [A study of sleep-waking rhythms based on pattern-recognition of continuous fetal heart rate monitoring]. AB - Two different rhythms exist in the fetal heart rate (FHR) pattern of a full-term fetus. These rhythms seem to be related to the rhythms associated with sleep and wakefulness, but the results are not yet conclusive. In this study, at first, the states of sleep and wakefulness in newborn infants (measured simultaneously by EEG, EOG, respiration and body movement) were compared with their heart rate patterns in rest, active, awake and unclassified phases. The results suggest that in newborn infants it is possible to distinguish quiet sleep from other states of sleep and wakefulness by means of the heart rate pattern alone. In the second part of the study, NST for three consecutive hours with 24 to 41 week pregnant women was performed and examined to determine the relationship between maturity and heart rate pattern (measured minute by minute in rest, active and unclassified phases) in their fetus. The findings suggest that the rest phase in a heart rate pattern of a fetus indicates the fetus to be in a state of quiet sleep. Further, the proportional increase and significant increase in the duration of the rest phase after 34 gestational week indicate the maturity of the central nervous system of the fetus. PMID- 2584823 TI - [Assessment of osteopenia following oophorectomy by quantitative computed tomography and its relation with Ca-regulating hormones]. AB - In order to determine the pathogenesis of post-oophorectomy osteopenia, we investigated the bone mineral status and biochemical parameters, and identified high-turnover bone metabolism. The present study was undertaken to determine whether there is a decrease in bone mineral content of peripheral bone or axial bone and cortical bone or trabecular bone using the microdensitometry method and a modified quantitative computed tomography method in 40 [24 premenopausal females (controls) and 16 premenopausal females who underwent oophorectomy]. We also investigated what biochemical and endocrinological parameters are changed, for example, Ca-regulating hormones and sex steroids, etc. As a result, it found that the reduction in bone mineral content due to oophorectomy occurs mainly in the axial bone, especially in the trabecular bone. It was considered that oophorectomy causes high-turnover osteopenia, in which bone formation is promoted but is outweighed by bone resorption, resulting in an overall decrease in bone mineral content. It also seemed that E2 is significantly related to bone metabolism, causing insufficient suppression of bone resorption. However, Ca regulating hormones appeared not to be directly related to bone metabolism during the period (average: 39.6 months) after oophorectomy. PMID- 2584824 TI - [DNA synthesis by growth factors in primary cultures of human trophoblast cells]. PMID- 2584825 TI - Establishment of human uterine sarcoma in nude mice. PMID- 2584826 TI - [An evaluation of two postoperative chemotherapy protocols in ovarian common epithelial cancer: a comparison of continuous and intermittent hospitalization]. PMID- 2584827 TI - [Clinical application of skeletal scintigraphy and quantitative computed tomography (QCT) to osteoarthritis of the knee]. AB - Skeletal scintigraphy and QCT were performed to determine changes of subchondral bone tissues in osteoarthritis of the knee and findings were compared with plain X-ray findings, knee pain and femoro-tibial angle. Results on blood pool study were especially related to pain. Results on delayed study using single photon emission computed tomography revealed high uptake on the medial side of the femur and tibia parallel to plain X-rays and pain. The QCT value was slightly decreased as osteoarthritic changes progressed without a significant change. In addition, delayed study in cases with previous surgical intervention by high tibial osteotomy revealed a lower uptake on the medial side of the femur and tibia. When skeletal scintigraphy accurately reflects blood flow through the subchondral bone tissues and is closely related to morbidity and pain, this modality is valuable in analysis of signs and symptoms as well as postoperative outcome. PMID- 2584828 TI - [Participation of osteoporosis in femoral neck fracture--bone mineral measurement of proximal femur using quantitative computed tomography]. AB - Quantitative computed tomography (QCT) was used to measure bone mineral contents of the proximal femur. First, 62 specimens of cancellous bones of the proximal femur obtained at operation were burnt for mineral determination after preoperative QCT measurement to evaluate the relationship between QCT values and ash weight. The findings indicated that QCT measurement of proximal femur was as useful as that of the lumbar spine. Next, 10 groups of 50 men and 50 women ranging in age from the 5th to the 9th decade were tested to define the control mean and range of QCT mineral content of proximal femur, to compare with 32 cases of femoral neck fracture. In women with femoral neck fracture, QCT values of the femoral neck were less than those of the same normal age group except for cases of medial fracture in the 9th decade. This measurement might provide an index for fracture risk. PMID- 2584829 TI - [Stress analysis of the femur after osteosynthesis of a trochanteric fracture using the finite element method]. AB - A stress analysis of the femur was performed in cases of the trochanteric fracture using the two-dimensional finite element method after osteosynthesis with the Ender nail, Jewett nail, AO angle plate and compression hip screw and the dynamic characteristics were discussed. Following results were obtained. (1) The Ender method makes maximum principal stress in the trochanter relatively small compared to the other methods. It also makes stress distribution of the femoral shaft rather stable. (2) The Ender method makes maximum extreme fiber stress in the device the largest compared to the other methods. (3) In the cases with weak abductor muscular force toward a fractured part, the Ender method is rather safe. In the cases with too strong abductor muscular force toward a fractured part, breaking of the device may occur. (4) Insertion of the Ender nails into the greater trochanter is effective in cases with large moment centering inside a fracture, as in a reverse intertrochanteric fracture. PMID- 2584830 TI - [A clinical study on the diagnosis of spinal cord tumor using magnetic resonance imaging]. AB - Thirty-five patients with a variety of spinal cord tumors were studied by magnetic resonance imaging (MRI). In 22 out of these cases, the efficacy of Dimeglumine gadopentetate (Gd-DTPA) in enhancing MRI was also investigated. The results were as follows: (1) MRI was capable of discerning the level of tumors. (2) MRI was able to distinguish intramedullary from extramedullary tumors. MRI, however, could not always differentiate extradural from intradural tumors. (3) Some cases of lipoma, arteriovenous malformation and hematoma were diagnosed by MRI. (4) Gd-DTPA was found to be effective in enhancing MRI in all cases of spinal cord tumors with exception of two cases of arteriovenous malformations. In conclusion, MRI is very useful in diagnosing spinal cord tumors. MRI, when enhanced with Gd-DTPA, is capable of revealing the content of tumors but also differentiating intramedullary tumors from surrounding edema and syrinx. PMID- 2584831 TI - [Detection of c-sis transcripts and PDGF-like products by in situ hybridization and immunohistochemical study]. AB - To clarify the relationship between oncogene c-sis expression and tumorigenesis in human osteosarcoma, in situ hybridization and immunohistochemical studies were performed to detect c-sis mRNA and PDGF-like protein partially consisting of c sis product. Formalin fixed-paraffin embedded sections of eight cases of osteosarcoma of bone were examined. Three osteosarcomas highly expressed c-sis mRNA with a fine granular pattern in their cytoplasms. Five osteosarcomas, including three cases with c-sis expression, contained PDGF-like protein in their cytoplasms. These results suggested that c-sis oncogene and PDGF-like protein were closely related to tumorigenesis in human osteosarcoma. The DNA-mRNA in situ hybridization technique applied by the author is as efficient as the immunohistochemical method in cancer research. PMID- 2584832 TI - [Measurement of changes in distance between the femoral and the tibial drill holes for the anterior cruciate ligament reconstruction]. AB - We have developed an experimental system in which a new Gallium-Indium containing transducer can continuously measure the changes of separation distances between the femoral and tibial points. The measurements provides information for the attachment location in the anterior cruciate ligament (ACL) reconstruction and used for various combinations of extra-articular and intra-articular methods. At the first experiment, the distance between each pair of points at the level of the capsule for fifteen combinations during simple flexion-extension knee motion were measured on six cadaveric knees. At the next experiment, in an ACL-deficient knee the distances of ten combinations in the intra-articular method were measured. These results indicated that for an isometric placement the combination of the center of tibial insertion and the postero-proximal of the femoral origin of the ACL appeared to furnish a better location for intraarticular reconstruction. No combination was recommended for extraarticular reconstruction. PMID- 2584834 TI - [Experimental studies on haematogenous osteomyelitis due to Staphylococcus hyicus in mice]. AB - 10(7) colony forming units of 18 different strains of Staphylococcus hyicus were intravenously administered into mice. Five mice as a group received each strain of S. hyicus. At 14 days after inoculation, 11 out of 18 strains were found in the bone marrow. Out of these 11 strains, SMUH 10 and SMUH 18 caused remarkable inflammation which was characterized by roentgenographical change. A number of these organisms were detected in the bone marrow until 28 and 42 days after the injection, suggesting specific lodgement of the strain in mouse bone marrow. X rays of the upper and lower extremities taken 14 days after inoculation showed multiple small radiolucent areas surrounded by small rims representing osteosclerosis. However, these changes did not show any aggravation during 70 days after inoculation suggesting tendency of improvement. PMID- 2584833 TI - [An experimental comparative study of hydroxyapatite and tricalcium-phosphate as bone substitutes]. AB - Hydroxyapatite (HAP) and beta tricalcium-phosphate (TCP) were implanted into the femoral distal metaphysis of 18 adult mongrel dogs. X-ray pictures were periodically taken following surgery, and the animals were sacrificed at 2, 4, 8, 12, 24 weeks, and 1, 2 years postoperatively. The undecalcified specimens were stained using Cole HE stain. During 2 years following surgery, both radiological and macroscopic examinations revealed no significant change in either HAP or TCP. In the undecalcified specimens, an apparent change in configuration was only noticed in the TCP, but there was no difference in the degree of new bone formation between HAP and TCP implants. At 2 years postoperatively, the Ca/P ratios of the HAP and TCP implants remained constant. The results of this study therefore suggest that TCP is a promising autograft extender. PMID- 2584835 TI - A new method of socket wear measurement in Charnley total hip replacement. AB - A new technique of wear measurement of the Charnley type socket is developed and introduced with an evaluation of its advantages and reliability. The principle in this technique is as follows: the X-ray projection angle of the radiograph taken before wear is corrected by some calculations on the basis of the second radiograph taken after wear has occurred. Then, on the identical X-Y coordinate axes made on these films, the shift of the femoral head's center (that is the wear vector) reveals the amount and direction of socket wear. When experimental wear of a socket was measured with this technique, the amount of wear was found accurate independent of varying socket fixating angle or irradiating direction. This technique has certain problems including technical complexity and the need for a new radiograph. However, it is useful clinically, because two-dimensional evaluation of socket wear both in amount and direction is possible. PMID- 2584837 TI - [Study on the surface quality of prosthetic hip joints]. AB - To evaluate the quality of the joint surface of a prosthetic hip joint, such parameters were measured as roundness, sphericity and roughness of joint surfaces for conventional prosthetic hip joints. Roundness was measured at two cross sections for spherical and semi-spherical parts; sphericity was deduced from measurements at 25 points using a coordinate measuring machine, and surface roughness was estimated from measurements at two points on the joint surface. The measured values were ranked in three levels, A (five marks), B (three marks) and C (one mark). The marks were totaled for a given prosthetic hip joint, and classified into the following 4 stages as a criterion for evaluation. The stages comprised A (more than 21 marks), B (20 to 18), C (17 to 15) and D (less than 14). The prosthetic hip joint evaluated as A has, on average, roundness, sphericity and roughness of the femoral head and acetabular cup, respectively of less than 0.1 and 20 microns, 5 and 50 microns, and 0.1 and 0.5 microns. (The maximum roughness of the acetabular cup was less than 5 microns.) Only a few products ranked A not only in individual measurements, but also in the total evaluation. This fact strongly supports the view that to be an effective product a prosthetic hip joint should meet at least the A criteria set up for evaluating the surface quality of its femoral head and acetabular cup. PMID- 2584836 TI - [A roentogenographical study on the alignment of the lower extremities in secondary coxarthrosis]. AB - Alignment of the lower extremities in secondary coxarthrosis (273 lower extremities) and controls (240 normal lower extremities) were studied using roentogenograms of whole lower extremities including the pelvis taken in the standing position with both legs. Secondary coxarthrosis, which is caused by congenital dislocation of the hip joint, was classified into four groups: unreduced dislocation, high dislocation, incomplete dislocation, and dysplasia of the acetabulum. Comparative studies were conducted using statistical data on measured items, obtained from secondary coxarthrosis cases and controls. In controls, the femoro-tibial angle (FTA) was 175.5 +/- 2.08 degrees and the mechanical axis passed through the medial side to the middle of the knee. It has been noted that a tendency for bow-legs was seen after the age of 50. In coxarthrosis with high dislocation, the most marked knock-knees were observed (FTA of 172.5 +/- 3.88 degrees), while in coxarthrosis with incomplete dislocation and dysplasia of the acetabulum, there was a tendency to coxa valga but no tendency toward knock-knees was evident. Cases of total hip replacement revealed that it is possible to improve knock-knees by installing a socket in the primary acetabulum as much as possible, correcting the difference between the length of the legs and elimating adduction contracture. It was also possible to study factors contributing to bow-legs and knock-knees by means of multivariate analysis. PMID- 2584838 TI - [Histopathological study of the aging process in the human sacroiliac joint]. AB - It has not been well defined the morphologic characteristics of the aging process of the sacroiliac joints in man. We have, therefore, studied the sacroiliac joints of human subjects by light and scanning electron microscopy. The joints were collected from 55 Japanese fetuses and adult cadavers. The articular cartilages on both sacral and iliac sides were composed of hyaline cartilage in the fetuses and adults. In fetuses, loose fibrous strands were found in the articular space and appeared to represent a residue of the intermediate layer during formation of the articular space. In adults who were older than 30, the joints showed definite degeneration which was more severe on the cartilage at the iliac side than that of sacral side. Scanning electron microscopic observations supported the light microscopic findings. Fusion of the two articular surfaces was observed in 24% of the adult joints. These findings strongly suggest that the buffering capacity of the sacroiliac joints decreases with aging which appears to relate to the clinical symptom of low back pain. PMID- 2584839 TI - [Study on the intraneural topography of the brachial plexus]. AB - To accurately determine the intraneural topography at each level of the brachial plexus, the funicular pattern of the brachial plexus in 10 Japanese adult cadavers was investigated by microdissection and an intraneural topographic map at different levels of the brachial plexus was prepared. It was possible to identify the intraneural location of funiculi from the cord level to the distal level of the nerve root. At the cord level, the funiculi were very thin and the funicular pattern was complicated. At the level from the division to the root, some nerve fibers were mixed. The intraneural topographic map of the C5 nerve root appears to be most important for cable grafting. In the C5 nerve root, the funiculus of the suprascapular nerve was located cranially, funiculi containing the musculocutaneus nerve anteriorly and those containing the axillary nerve posteriorly. PMID- 2584840 TI - [Effect of the sympathetic nerve on the skeletal muscle blood flow at rest, during and after contraction]. AB - The effects of the sympathetic nerve on the muscle blood flow were studied on the quadriceps muscles of anesthetized rabbits. The muscle blood flow was measured by heated thermocouple technique, electrolytic hydrogen clearance method and laser doppler flowmetry. There was significant correlation in the muscle blood flow measured by the above three methods. After blockage of the neuro-muscular junction with pancuronium bromide, the femoral nerve stimulations with pulse duration 0.1 msec, 6 V, at 2, 5 and 10 Hz caused no change in the muscle blood flow, while the stimulation with pulse duration 1 msec, 6 V, at 10 Hz caused reduction of the muscle blood flow. The higher the frequency of lumbar sympathetic trunk stimulation was, the lower the muscle blood flow became thus the longer the recovery time was. When femoral nerve and lumbar sympathetic trunk were stimulated simultaneously, increment of muscle blood flow during contraction became less prominent, especially, with a stimulation of 5 Hz, which caused a decrement of post-contraction hyperemia both in height and duration. These results suggest that sympathetic nerve activities have an influence on the muscle blood flow at rest, as well as during and after muscle contraction. PMID- 2584841 TI - [Peroxide lipid and evoked spinal potentials in experimental spinal cord ischemia]. AB - The author of this report has studied peroxide lipid and evoked potentials of the spinal cord during ischemia and after reperfusion. In addition, he has studied effects of vitamin E (V.E.) upon ischemic spinal cord. The ischemia of the spinal cord was experimentally produced by clamping the thoracic aorta of Wistar rats and subsequently removing the clamps. Wistar rats were given diet containing 2 IU/100 g (control group) or 50 IU/100 g (V.E. group) of alpha-tocopherol acetate for 6 weeks before experiments. In the V.E. group the quantity of thiobarbituric acid reactive substance (TBARS) in the spinal cord after clamp removal was lower than the control group. The V.E. content in the spinal cord indicated a negative correlation to the TBARS values. The evoked spinal potentials in both groups disappeared due to spinal cord ischemia. The control group displayed wave form loss earlier than the V.E. group. It is conceivable that lipid peroxidation correlate to the tissue damage following spinal cord ischemia and reperfusion, and V.E. has the preventive effect to the damage. PMID- 2584842 TI - [Molecular biological approach to orthopaedic research--analysis of cartilage collagens]. PMID- 2584843 TI - The ethical issues of medicine. PMID- 2584844 TI - Double jeopardy: the diagnosis and treatment of pulmonary thromboembolism in pregnancy. AB - Current information about deep vein thrombosis and pulmonary embolism indicates that both conditions are greatly underdiagnosed. Since some of the newer methods for accurate diagnosis constitute a potential hazard to the fetus, underdiagnosis is most assuredly true for pregnant patients as well. The diagnostic approach to the pregnant female suspected of having pulmonary thromboembolism is discussed and the current treatment recommendations are reviewed. PMID- 2584845 TI - Pancreatic abscess: analysis of a high risk subgroup. AB - Over the past ten years, 21 cases of pancreatic abscess were diagnosed at our university teaching hospital. On the basis of the findings from CT scan, sonography, and exploratory laparotomy, five patients were determined to have poorly localized disease and 16 patients were felt to have well localized purulent fluid collection. The five patients with poorly localized disease had an overall mortality rate of 80%, an average of 5.2 Ranson criteria, and 80% required partial pancreatic resection. Of the 16 patients with well localized disease there was a mortality rate of 20%, an average of 3.3 Ranson criteria, and only 6% required resection. All five patients who had pancreatic resection died. These data suggest the following conclusions: 1. Patients with pancreatic abscess which is poorly localized have a greater severity of pancreatitis as indicated by a higher average number of Ranson criteria. 2. Patients with a poorly localized phlegmonous abscess more often require pancreatic resection, which is associated with a higher mortality. 3. The high mortality rate seen with patients with a poorly localized phlegmonous pancreatic slough designates this group as a high risk subset of all pancreatic abscess patients. PMID- 2584846 TI - Promoting the appropriate use of medications by older adults; the pharmacist's role. PMID- 2584847 TI - Resuscitation. PMID- 2584848 TI - Traumatic middle ear lesions. Fracture of the malleus handle, aetiology, diagnosis and treatment. AB - Traumatic middle ear lesions are quite common but only seldom mentioned in the literature; an isolated fracture of the handle of the malleus seems to be extremely rare. The appearance of two patients with an isolated fracture of the handle of the malleus within one year might indicate that this type of lesion should be considered more frequently. The traumatic aetiology, symptoms, diagnosis and treatment of this lesion is described and is illustrated by two cases. PMID- 2584849 TI - Serum antibodies against respiratory tract viruses: a prospective three-year follow-up from birth. AB - Acute otitis media (AOM) has been epidemiologically related to viral respiratory tract infections, and viral antigens have also been detected in middle ear secretion in some AOM episodes. Successive serum samples from children followed prospectively for three years from birth were analysed for IgG antibodies against respiratory syncytial virus (RSV), adenoviruses and influenza A virus. Values from serum antibody activity gradually decreased during the first six months of life, followed by a gradual increase. Various relationships were found to obtain between age and the increases of antibody activity against the different viruses. Thus, three quarters of those tested had manifested increased antibody activity against RSV by 18 months of age, and against adenoviruses by 30 months of age. No increase of antibody activity against influenza A was noted before 12 months of age, and then only seen in two thirds of those tested during the entire three year observation period. With regard to age, however, the proportion of children with increased antibody activity to RSV, adenoviruses or influenza A virus did not differ between otitis-prone and non-otitis-prone children. Thus, as compared to non-otitis-prone children, development of the ability to produce antibodies against these viruses was not found to be delayed in otitis-prone children. PMID- 2584850 TI - Nasal airflow: resistance and sensation. AB - For many years nasal resistance to airflow measured by rhinomanometry has been regarded as the objective measure of nasal patency. However, recently it has become apparent that this may not be the case. The present study was designed to affirm or refute this view by using large numbers of subjects and observations. Five hundred estimations of (objective) nasal resistance to airflow and (subjective) nasal sensation of airflow where carried out. No correlation could be demonstrated between these two parameters. It is concluded nasal resistance to airflow and nasal sensation of airflow are two separate modalities which are not directly related. The possible reasons for this finding are discussed with reference to previous work on nasal sensation. PMID- 2584851 TI - Total glossectomy: reconstruction and rehabilitation. AB - Patients with carcinoma of the tongue including the base of the tongue who underwent total glossectomy in a period of just over ten years since January 1979 have been reviewed. Total glossectomy may be indicated as salvage surgery or as a primary procedure. The larynx may be preserved or may have to be sacrificed depending upon the site of the lesion. When the larynx is preserved the use of laryngeal suspension facilitates early rehabilitation and preserves the quality of life to a large extent. Cricopharyngeal myotomy seems unnecessary. PMID- 2584853 TI - Laryngotracheal resection for post scleromatous laryngeal stenosis. AB - Scleroma is an endemic disease in Egypt, which frequently results in subglottic laryngeal stenosis. Six patients suffering from laryngoscleroma are represented. They all underwent laryngotracheal resection of the stenosed segment, followed by direct anastomosis. The results were satisfactory in four of the patients. Surgery was abandoned in one patient who was believed to suffer from perichondritis following previous surgery. Restenosis occurred in a 14-year-old girl two weeks after surgery. This was attributed to recurrence, possibly due to residual activity of the disease which was missed before surgery. PMID- 2584852 TI - The lingual tonsil. A neglected symptomatic structure? AB - Surgical treatment of the lingual tonsil is seldom performed because problems attributable to chronic lingual tonsillar hypertrophy are infrequently diagnosed. We have reviewed a series of 25 patients with symptoms from enlarged lingual tonsils. The variety of presentation of lingual tonsillar lesions and the methods of surgical treatment are discussed. PMID- 2584854 TI - An evaluation of myringoplasty in war injured people. AB - Perforation of the tympanic membrane is a common war injury, especially after explosions. Such perforations will normally heal spontaneously under favourable conditions. A small number in whom the defect persists will benefit from closure by myringoplasty. Thirty-four such cases underwent operative repair and were compared with an equal number due to other causes. PMID- 2584855 TI - Klippel-Feil syndrome and conductive deafness. AB - The Klippel-Feil syndrome is usually associated with sensorineural deafness and reports of conductive or mixed deafness are rare. Four additional cases are presented in this paper. The middle ear anomalies found in this syndrome are discussed. The results of middle ear surgery are reviewed and found to be poor. PMID- 2584856 TI - Alveolar soft part sarcoma of the tongue. AB - In this report a 13-year-old girl with characteristic clinical and pathological features of alveolar soft part sarcoma of the tongue is presented. Alveolar soft part sarcoma is a rare malignant tumor of unknown origin. Forty eight cases of alveolar soft part sarcoma have so far been reported in the head and neck region. Median survival reported for all sites of the body is 79 months following various modes of therapy. In this case, the treatment was surgical excision of the mass combined with radiotherapy and chemotherapy. The patient has been asymptomatic for the past 12 months. PMID- 2584857 TI - Parapharyngeal mass presenting with sleep apnoea. AB - A 60-year-old man presented with a history of progressive sleep disturbance due to an intraoral parapharyngeal salivary gland tumour. The sleep study performed post-operatively showed rapid resolution of nocturnal hypoxic episodes. This appears to be the first recorded case of a parapharyngeal mass causing sleep apnoea and we review the current literature on obstructive sleep apnoea. PMID- 2584858 TI - Pharyngeal cyst arising from second branchial cleft. AB - A rare case of pharyngeal cyst arising from the second branchial cleft in a 14 year-old boy is described. A cyst located in the right posterolateral wall of the oropharynx was completely removed by an intraoral approach. Histopathological examination revealed that the cyst was lined with columnar (respiratory type) epithelium. PMID- 2584859 TI - Congenital cysts of the larynx. AB - Two cases of congenital cyst of larynx which is a rare condition, are reported. PMID- 2584860 TI - Recurrent laryngeal nerve palsy following heart-lung transplantation: three cases of vocal cord augmentation in the acute phase. AB - Three cases of left recurrent laryngeal nerve palsy following heart-lung transplantation are described. In each case, within twelve hours of extubation, the left vocal cord was injected with Teflon, and the paralyzed vocal cord thus displaced to the midline. Effective closure of the glottis was then possible, permitting an adequate cough, adequate clearing of the bronchial tree and minimising the risk of aspiration. Augmentation under general anaesthesia as soon as possible after discovery of vocal cord dysfunction is advocated. Suitable materials for injection are discussed. To our knowledge, this is the first reported series of vocal cord augmentation in the acute phase following heart lung transplantation. PMID- 2584861 TI - Laryngeal chondrosarcoma: is conservative surgery adequate treatment? AB - A case of laryngeal chondrosarcoma in a 63-year-old woman is presented. The report illustrates most of the features of this rare neoplasm, the difficulties in the histopathological evaluation and supports the previous ones that recommend an initial conservative attitude towards low grade laryngeal chondrosarcomas. PMID- 2584862 TI - Facial schwannoma without facial paralysis. AB - A 64-year-old man with right aural discharge presented complaining of progressive deafness. Other otological symptoms were absent and specifically there was no seventh nerve paresis. A right aural polyp was identified and biopsied. Histology showed the polyp to be a schwannoma. Subsequent temporal bone computed tomography showed expansion of the distal facial canal. At operation, the schwannoma filled the middle ear cleft and extended from the genu to the region of the stylomastoid foramen. The floor of the middle ear had been eroded, exposing the jugular bulb. Facial paresis is the usual presenting feature of a facial schwannoma, while deafness, ageusia and reduced lacrimation are variable, dependent upon the site of the lesion. The absence of facial palsy as a presenting feature is very rare and this case illustrates the need for histological examination of all abnormal aural material. PMID- 2584863 TI - Adenosquamous carcinoma of the thyroid gland. AB - A case of adenosquamous carcinoma of the thyroid gland is presented. This rare form of cancer behaves in an aggressive manner similar to anaplastic carcinoma and is characterized histologically by the intimate blending of the squamous and glandular elements. The prognostic significance of identifying areas of malignant squamous epithelium within papillary carcinoma as opposed to the much more common benign squamous metaplasia, is highlighted. The pathogenesis, differential diagnosis and management of the condition are discussed. PMID- 2584864 TI - CSF otorrhoea secondary to a tegmen defect. PMID- 2584865 TI - Tuning forks: the origin of interfering waveforms. PMID- 2584866 TI - Guillotine and dissection tonsillectomy compared. PMID- 2584867 TI - Anthropological study of the mastoid air cell system in Pakistani races. AB - This is an anthropological study of the development of the mastoid process in the four ethnic groups of Pakistani races: Turko-Iranian, Indo-Aryan, Scytho Dravidian, and Aryo-Dravidian. Cephalometric studies have established that the majority of Pakistanis are brachio to ultra-brachiocephalic (Cephalic Index 82 x). Radiological evaluation of normal mastoids and their planimetric measurements show that the mastoid process is smaller (Av: 10.24 sq.cm. +/- 0.8) than the Caucasian Western races (Av: 12-15 sq.cm.). Neither combined approach tympanoplasty, nor mastoid obliteration technique may be required, nor technically possible in a small mastoid. Natural epithelization of a small 'peanut size' mastoidectomy cavity does not justify these procedures. A modified radical mastoidectomy and tympanoplasty reconstruction provides a satisfactory result in chronic discharging ears. PMID- 2584868 TI - Diagnostic vetting of individuals with asymmetric sensorineural hearing impairments. AB - Audiological and vestibular tests were administered conjointly in a neurological or general ORL clinic to exclude cerebellopontine angle (CPA) tumours. This study aimed to assess the efficiency of various tests in achieving that exclusion with the minimum of unnecessary investigations. All patients received the full battery of auditory brainstem responses, acoustic reflex thresholds and decay, alternate binaural loudness balance and ENG and caloric testing. All patients who did not have normal auditory brainstem responses proceeded to high resolution CT scanning. One hundred and fifteen patients were investigated and four acoustic neuromas were diagnosed. The efficiency of these tests in a general ORL clinic is very much poorer than often suggested, due largely to the number of occasions on which the tests cannot be done, and to the very small proportion of the test population who have CPA tumours. PMID- 2584869 TI - Otitis media with effusion as a presenting symptom of chronic sinusitis. AB - Otitis media with effusion was the presenting symptom in 23 per cent of patients suffering from chronic sinusitis. The inter-relationship between chronic sinusitis and otitis media with effusion was studied in 29 patients. Endoscopic evaluation of intranasal structures including sinus ostia and Eustachian tube orifices was carried out. We further suggest that otitis media with effusion is not a separate entity but a presentation of sinus disease, predominantly of the ethmoid system. Patients with otitis media with effusion should be evaluated for sinusitis and vice versa. The value of careful nasendoscopy is demonstrated. PMID- 2584870 TI - Temporal bone laboratory training for stapedectomy. AB - Practice in the Temporal Bone laboratory is a fundamental part of Otological training. Performing a stapedectomy on a normal temporal bone is handicapped by the mobility of the footplate. We describe a simple method of producing stapes footplate fixation in a normal temporal bone so that the operative conditions found in otosclerosis are more closely simulated. PMID- 2584871 TI - Contralateral auditory brainstem response abnormalities in acoustic neuroma. AB - Contralateral Auditory Brainstem Response (ABR) findings in a series of 79 patients with unilateral acoustic neuroma are presented. Sixty-four patients (81 per cent) had a normal contralateral ABR, thirteen (16.4 per cent) had latency abnormalities contralaterally and in two patients (2.6 per cent) no consistent responses could be recorded despite good hearing. Abnormalities in the contralateral ABR were analysed and five patients had abnormal III-V interwave intervals, in seven patients the I-III intervals were abnormal and in one patient, only the fifth wave was present and of abnormal latency. The tumour size was assessed by computed axial tomography (CT) and the relationship between tumour size and contralateral ABR findings established. Large tumours (greater than 2.5 cm.) were associated with contralateral ABR abnormalities in 25.6 per cent of the patients, medium tumours (1.0-2.5 cm.) with ABR abnormalities in 14 per cent and there were no abnormalities in the small group (intracanalicular). The implications for interpretation of ABR recordings contralateral to an acoustic neuroma are discussed in relation to brainstem compression and its effect on the wave generator sites. PMID- 2584873 TI - Transmastoid extracranial repair of CSF leaks following acoustic neuroma resection. AB - Acoustic neuromas may be resected either by a suboccipital craniectomy or translabyrinthine approach; the latter gives good access without unduly traumatising the brainstem, but can lead to a higher incidence of cerebrospinal fluid (CSF) leaks. The surgical management of these leaks can be difficult; we describe a transmastoid extracranial technique using pedicled sternomastoid muscle that has produced complete resolution of the leak in all cases managed in this way. PMID- 2584872 TI - Unterberger's stepping test in acoustic neuroma. AB - A prospective study of 100 patients with a unilateral, subsequently histologically proven, acoustic neuroma seen in the Department of Otoneurosurgery at Addenbrooke's Hospital between 1983 and 1988, demonstrated that Unterberger's Stepping test achieved a higher sensitivity (71 per cent) than the Romberg test (39 per cent). The discrepancy between tests is at a maximum for small acoustic neuromas, and therefore the Stepping test may help in the earlier detection of vestibular abnormalities. PMID- 2584874 TI - The contralateral ear after translabyrinthine removal of acoustic neuromas: is there a drill-noise generated hearing loss? AB - To determine whether translabyrinthine acoustic surgery may result in a drill generated, bone-conducted sensorineural hearing impairment in the contralateral ear, the audiograms from 50 consecutive patients with acoustic neuromas undergoing the translabyrinthine approach were compared before and three months after surgery. No case of sensorineural hearing impairment could be demonstrated postoperatively. PMID- 2584875 TI - Hearing aids--a case for review. AB - An analysis of a series of 100 patients aged 60 years or over, referred by their General Practitioner to the Department of Otolaryngology, Addenbrooke's Hospital, specifically for the provision of a hearing aid, is presented. Forty-six per cent of patients failed to satisfy the criteria suggested by the Technicians, Therapists and Scientists in Audiology as a screening for treatable pathology. This study has shown that the existing referral pattern of general practitioner to consultant otolaryngologist for the provision of a hearing aid reflects the highest quality of care for the patient. Direct referral or open access of patients for hearing aid fitting may risk failure to diagnose early and treatable conditions. PMID- 2584876 TI - Nasal mucociliary clearance in patients with diabetes mellitus. AB - Fifty insulin-dependent diabetics and 50 non-diabetics without a history of nasal disease have been studied for nasal problems including mucociliary function complicated by diabetes mellitus. For the diabetics, the mean value of nasal mucociliary clearance was considerably decreased and this was more often associated with dry noses but increased pH-values, both of which were higher than those for non-diabetics (p less than 0.05). As suggested in earlier literature, more aggressive nasal moistening therapy must be recommended for those patients presenting with these conditions in the light of systemic diabetic abnormalities. PMID- 2584877 TI - Antroscopy in maxillary sinus disease associated with nasal polyposis. AB - Although the association of maxillary sinusitis with nasal polyps is widely recognized little has been written on its precise incidence and degree. Antroscopy of 70 antra with ipsilateral polyps showed a high incidence of mucosal abnormalities, retained secretions and ostial narrowing. Comparison of these findings with preoperative X-rays showed the latter were unreliable in detecting retained antral fluid. It is concluded that in nasal polyposis the antra warrant careful assessment and that antroscopy is a highly satisfactory method for this purpose. PMID- 2584878 TI - Laryngeal tuberculosis in the eighties--an Indian experience. AB - Laryngeal tuberculosis is one of the rarer forms of extrapulmonary tuberculosis. A retrospective analysis of 26 patients seen in the last nine years in our hospital was conducted to illustrate the various modes of clinical presentation. Of the 26 patients, twenty were male and six female. The average age of presentation was 47 years with an age range of 15 months to 71 years. Hoarseness (92.3 per cent) was the commonest symptom. The laryngoscopic appearances often simulated malignancy. Most patients (69.2 per cent) had lesions involving the anterior two-thirds of the true vocal cords. Hypertrophic lesions (69.2 per cent) out-numbered ulcerative ones (38.5 per cent). Laryngeal oedema was infrequent (7.7 per cent). Diagnosis was based on a laryngeal biopsy in 18 patients and on evidence of associated pulmonary tuberculosis and response to anti-tuberculous therapy in eight. Chest X-rays showed apical cavitation and infiltration as the commonest findings. Three patients had miliary tuberculosis and one had no pulmonary lesion. Diabetes mellitus was present in seven (26.9 per cent) patients. Four illustrative cases are described. The problems in diagnosis and management of laryngeal tuberculosis are discussed. PMID- 2584879 TI - Subarachnoid fat embolism complicating autologous fat grafting following translabyrinthine excision of acoustic neuroma. AB - A 64-year-old man had complete excision of an acoustic schwannoma via the translabyrinthine route and the mastoid cavity was packed with fat. Post operatively there were two episodes of aseptic meningitis and CT scanning demonstrated migration of fat into the basal subarachnoid CSF spaces. This unusual complication should be recognized and differentiated from both true infective meningitis and aseptic meningitis from other causes. PMID- 2584880 TI - Objective tinnitus and tympanic membrane displacement. AB - A young girl with objective tinnitus is presented. Using tympanic membrane displacement, the probable origin of the tinnitus has been demonstrated. The patient has responded well to treatment with a tinnitus masker. PMID- 2584881 TI - Factitious illness and the ENT surgeon. AB - Factitious illness' is a recently classified group of diseases characterized by repeated purposeful simulation of physical or mental illness in order to obtain medical or psychiatric treatment. 'Munchausen Syndrome' is a classical example of this group. The case reported is a 26-year-old Caucasian male who presented with recurrent facial swelling between December 1978 and November 1987. His true condition eluded diagnosis for so long because he presented repeatedly with overt clinical signs which appeared severe enough to justify the symptoms claimed. PMID- 2584882 TI - Metastatic melanoma of the tonsil. PMID- 2584883 TI - [How to assure the international future of medical and scientific Francophone periodicals]. PMID- 2584884 TI - [Venous hemodynamics. Base equations]. AB - The hydrodynamics in tubes with inert walls collapsed by a negative transmural pressure (inside pressure minus outside pressure) set up a fundamental and original approach in venous hemodynamics. Mechanisms of flow regulation and flow limitation can occur especially when the upstream pressure is held constant or when the average flow speed in a cross-section equals the local pressure waves speed. The three baseline equations on mechanics are required to demonstrate these properties: --the tube law, --the equation of motion, --the equation of continuity. It is shown that the behaviour of the tube varies with the nature of the flow (subcritical, critical or supercritical, subsonic, sonic or supersonic, according to the aerodynamics). Though this study does not take all the physiological and biological data into account, it includes indeed the three fundamental aspects on mechanics of the veins. The rheologic equation on the state of the venous wall, normal or pathologic, plays a major and determinant role. PMID- 2584885 TI - [Thrombectomy or thrombolysis in the treatment of proximal phlebitis. Functional long term results]. AB - MATERIALS AND METHODS Between 1981 and 1985, 78 iliocaval thrombi were treated by aggressive therapy: 52 surgical thrombectomies were performed by a femoral approach associated, depending on the case, with a caval approach; and 26 iliofemoral thrombi were lysed according to a protocol in which urokinase and plasminogen were used over a 48-h period. Subsequent functional evaluation was based on clinical scoring (0 to 9 points) taking into account functional impairment, edema and trophic disorders. Patency of trunks and the deep valvular state were assessed by Doppler examination and plethysmography. RESULTS In the surgical group, 3 early deaths occurred, only one of which could be attributed to an embolic course. Six weeks after surgery the rate of recurrence of iliac thrombosis was 50% (25% postoperative + 25% secondary). Beyond this period, there were no recurrences of thrombosis. There was a direct, statistically significant relation between the degree of iliac patency and the realization of an ideal thrombectomy on a nonadherent fresh clot. The functional results, assessed after four and a half years of follow-up, are satisfactory (score less than 3) in 80% of patients. The poor results with venous claudication or varicose ulcer all occurred in the case of massive persistent thrombi of the femoral confluence. Valve lesions were signaled in 46% of patients by a massive backflow in orthostatism. In the medical group, a major hemorrhagic complication occurred under urokinase therapy in 11% of patients, including one for whom it was fatal. Sixty percent of patients showed immediate radiological improvement allowing partial or total freeing of a venous confluence. The functional results after 4 years of follow-up were nondisabling in 85% of patients. No leg ulcers were detected. Late iliac patency was low (26%), whereas at the femoral level almost all of the thrombi which remained after lysis became patent again spontaneously. Valve failure was found in 37% of patients. Both groups had very similar late functional results despite rather different anatomical conditions. The iliac patency rate was higher in the surgical group (50% vs 26%), but plethysmographic study showed that in case of therapeutic failure devalvulation was greater after surgery (46% vs 37%). PMID- 2584886 TI - [Action of nifedipine on the post-ischemic cold hyperemia reaction in Raynaud's phenomenon]. AB - PURPOSE OF THE STUDY: To determine the effects of Nifedipine on cold stress reactive hyperemia in patients with Raynaud's phenomenon. DESIGN: Open trial comprising an observation period without treatment and a treatment period with Nifedipine. SETTING: Referral-based angiology department in a university hospital. PATIENTS: 26 patients with definite Raynaud's phenomenon were included; 6 patients were withdrawn (3 for side effects, 1 for pregnancy, 2 for protocol inobservance). INTERVENTIONS took place after one week of observation and one week of treatment with Nifedipine per os 20 mg 3 times daily. At day 0, 7 and 14, cold stress was performed to measure cold reactive post-ischemic hyperemia. MAIN RESULTS: During the Nifedipine period, the number of attacks, their intensity and resulting total disability decreased significantly, and hyperemia increased significantly. CONCLUSIONS: Our study confirms improvement in Raynaud's phenomenon with Nifedipine. This calcium-channel inhibitory drug also improves cold reactive hyperemia. This new cold test is inexpensive and easy to perform and appears to be suitable for assessing hemodynamic objective improvement in drug trials concerning Raynaud's phenomenon. PMID- 2584887 TI - [Value of somatosensory evoked potentials in thoraco- brachial outlet syndrome]. AB - INTRODUCTION: Brachial plexus involvement in symptoms of thoracic outlet syndrome (TOS) is often difficult to assess from clinical data. Conventional EMG and nerve conduction studies (NCS) do not seem reliable to all authors. For this reason, our investigations of this syndrome were complemented by study of somatosensory evoked potentials (SEP) in order to compare the results of these different techniques. PATIENTS AND METHODS: Ten patients were studied, all of whom had prominent vascular symptoms which led to their consulting a vascular surgeon. Only one had hand wasting without hypoesthesia. None had cervical rib or cervical spine anomaly. In all cases, diagnosis was confirmed by arteriography or phlebography. Operations were decided on clinical data and results of vascular investigations. Patients were tested with conventional motor and sensitive NCS F wave studies. Needle EMG was performed in abductor pollicis brevis, first dorsal interosseus or abductor digitiminimi. Their SEP were performed as for controls. Ten controls were studied whose SEP were obtained at Erb's point (N9) and C2 cervical spine level (N13) after percutaneous stimulation of median and ulnar nerves at the wrist on both sides. The criterion of abnormality was the mean of controls + 2.5 SD for latencies. Amplitude was considered as low when it was less than 50% of the contralateral one. RESULTS: For 2 patients EMG, NCS and SEP were abnormal. One had hand wasting and denervation in hand muscles as well as slowed median and ulnar sensory conduction with low amplitude responses. SEP at Erb's point were slightly delayed after ulnar stimulation. No cervical response was obtained after ulnar stimulation. The second one had normal responses at Erb's point but delayed responses at the cervical level. In addition, N13 amplitude after ulnar stimulation was low. Four patients had normal EMG, NCS and SEP. Two patients had normal EMG and NCS, but their SEP was questionable since latencies were normal, even though amplitude was low after median and ulnar stimulation. This was not considered this to be abnormal since it was bilateral. For the remaining 2 patients (F.1), EMG and NCS and Erb's point SEP were normal, but C2 median and ulnar responses were delayed in one case and C2 ulnar response amplitude was very low on one side only in the other. In conclusion, SEP were abnormal for 4 patients out of 10 but gave more information than conventional EMG and NCS for only 2 patients. SEP abnormalities prevailed after ulnar stimulation. PMID- 2584888 TI - [Venous insufficiency and hemorheology. Influence of venous stasis on erythrocyte aggregation and disaggregation]. AB - The aim of this study was to assess the rheological properties of blood in patients with superficial venous insufficiency, in the very exact place of the hemodynamic disturbance i.e. in the veins of the lower limbs. MATERIAL AND METHODS: Several hemorheological parameters were studied in 20 patients (12 females and 8 males, 20 to 44 years old) with varicose veins of the lower limbs (insufficiency of the superficial venous system and no history of thrombosis). The results were compared to those obtained in 20 healthy controls matched for sex, age, weight and schedule for blood withdrawal. Two blood samples were obtained from the veins of the lower limbs of each subject: the first one at rest and the second after 10 minutes of "venous stasis" (standing position and 100 mm Hg tourniquet), in a temperature controlled room (22 degrees C). Every blood test was performed within one hour after blood withdrawal: --hematocrit (microcentrifugation) and fibrinogen (nephelometry); --plasma viscosity in a 37 degrees C temperature controlled capillary viscometer (Myrenne KSPV4); - erythrocyte filterability using the Hemorheometer (8% hematocrit and polycarbonate nuclepore membrane with a pore diameter of 5 microns); - erythrocyte aggregation and disaggregation (Myrenne AMM1 aggregometer and Erythroaggregometer SEFAM). RESULTS: 1. Hematocrit was not significantly different between both groups of subjects at rest. However, it increased significantly after venous stasis in patients with varicose veins (44.2% vs 41.8%, p. less than 0.05) and that was not found in controls. 2. At rest, the fibrinogen level was higher in patients than in controls (3.54 milligrams vs 2.41 milligrams, p less than 0.01). After statis, a significant increased was found only in the patients group (3.93 milligrams, p less than 0.05). 3. In a similar way, plasma viscosity at rest was significantly higher in patients (1.23 mPa.s) than in controls (1.11 mPa.s, p less than 0.01), and after stasis a further increase was found in the patients group (1.32 mPa.s, p less than 0.01). 4. Also the erythrocyte filterability index was altered at rest in patients (20.9) when compared to controls (15.1, p less than 0.01). A significant increase of this index was only found in the patients group (23, p less than 0.01). 5. Every aggregation parameters were significantly different at rest when comparing subjects groups, the most significant difference concerning the threshold of disaggregation (171.2 s-1 vs 106.8 S-1, p less than 0.001. Erythrocyte aggregation index was increased after stasis in patients but not in controls, with both 600 S-1 and 3 S-1 shear rates. 6. Positive correlations were found between low shear rate aggregation index on one hand and fibrinogen (r = 0.61), plasma viscosity (r = 0.51) and erythrocyte filterability index (r = 0.47) on the other hand... PMID- 2584889 TI - [Arterial sequelae of pregnancy hypertension. Detection by carotid piezogram]. AB - High blood pressure (HTA) is characterized by elevation of pression, but also by modifications of arterial pulse wave. Carotid piezograms were used to evaluate arterial pulse wave. Diastolic blood pressure is significantly correlated with dicrotic notch pressure. The duration of dicrotic notch is negatively correlated with arterial wall elasticity. Thus by carotid piezogram analysis one can determine the respective participation of arterial wall elasticity, peripheral resistance and cardiac factors in blood pressure elevation. Carotid piezograms were measured in 97 women (mean age 27, 8 y), with previous hypertensive pregnancy and apparently cured (mean blood pressure 122-74 mmHg at time of examination). 25 women only had normal piezogram drawing. Abnormalities similar to that of permanent hypertensive disease were observed in most cases. Dicrotic notch duration was significantly reduced and dicrotic notch pressure enhanced; in 34 women both of these abnormalities were present. In conclusion, among women previously hypertensive during pregnancy, even when blood pressure is returned to normal, abnormalities of arterial pulse wave may be present, suggesting that these women are prone to subsequent permanent hypertension. PMID- 2584890 TI - [Lumbar sympathectomy in the aged subject: surgery or phenolization? Prospective study of early results]. AB - Lumbar sympathectomy, which is usually indicated in the arteritic patient in cases of severe ischemia and occlusion of leg arteries when bypass surgery is not feasible, can be performed surgically or by scanner-guided phenolization. Surgical sympathectomy was performed by resection of the 2nd, 3rd, 4th and 5th lumbar ganglia under general anesthesia by a retroperitoneal route. Chemical sympathectomy involved scanner-guided injection of phenol diluted 6.7% into the sympathetic nervous system at L3 and L4 level. This act, performed on outpatients, required no anesthesia. Prospective study of the early results (within one month) obtained with these two techniques in 428 patients indicates that rates of death, amputation and noteworthy complications for those less than 70 yr (table IV, VI and VIII) were respectively 4.7%, 8.5% and 7.4% for surgery, and 2.5%, 5% and 0% for phenolization; for those greater than 70 yr the rates were respectively 12%, 11% and 10% for surgery, and 10%, 9% and 8% for phenolization. It may be concluded that phenolization of the sympathetic nervous system provides the same results as surgical sympathectomy but has the advantage of lower morbidity and shorter hospitalization (24 h vs 10 days). The results of these two techniques in terms of limb conservation are disappointing and markedly poorer than those of distal bypass surgery. PMID- 2584891 TI - [Arterial pathology of the limbs. Tests for hyperemia]. AB - We consider the walk test on the treadmill (ET), and the postocclusive reactive hyperemia (HR). The determinations are limited to the peripheral pressures measured by the sphygmomanometric-Doppler technique. It is the method of choice for diagnostic purposes, but is necessary only for selected cases. For epidemiology, HR is interesting because it is simple to apply and the sensitivity and specificity to recognise moderate obstructions is good. The determination of the ankle pressure at rest is generally enough in the routine practice. It is reproducible and safe. ET may be applied in certain conditions taking into account some problems of interpretation due the complexity of the phenomenon. PMID- 2584892 TI - [Variation of TCPO2 as a function of tobacco consumption in the healthy subject]. PMID- 2584893 TI - Itinerant surgery in the guise of outreach surgery. PMID- 2584894 TI - Massive orbital and intracranial teratoma in the newborn: a case report. AB - Severe hydrocephalus secondary to a massive teratoma occupying the left lateral ventricle and protruding from the left orbit was diagnosed in a newborn infant. A craniofacial mass had been initially detected during labor by ultrasound examination. The pathophysiology of teratomas and the clinical course and ethical issues in management of this child are discussed. PMID- 2584895 TI - Parental satisfaction with neonatal intensive care services. PMID- 2584897 TI - Retirement of a surgeon. Part I: Freedom and happiness. PMID- 2584896 TI - Continuing medical education requirements for hospital medical staffs. PMID- 2584898 TI - Taxpayer's Bill of Rights: much ado about nothing. PMID- 2584899 TI - Percutaneous umbilical cord blood sampling. AB - Percutaneous umbilical cord blood sampling is a newer, safer, and more convenient technique and can be performed in the second and third trimester of pregnancy by direct puncture of the umbilical vein near its placental insertion, using a needle guided by ultrasound. Between 2-4 ml of pure fetal blood were obtained from 10 pregnancies at between 19 and 39 weeks' gestation. This new procedure offers access to the fetal circulation for diagnosis and therapeutic purposes. PMID- 2584900 TI - Computed tomography in the diagnosis of central nervous system lymphomas. AB - CT appearances of 13 patients diagnosed as having CNS lymphoma were reviewed. Eight patients were of primary type and 5 patients had secondary CNS involvement. In primary CNS lymphoma, the median age was 62.5 years. All except one were male. Solitary lesions were observed in 4 patients; multiple lesions in 3 patients and an infiltrative lesion in one. Characteristic CT finding was a hyper-or isodense mass with homogeneous enhancement in the gray matter and corpus callosum. In secondary CNS lymphoma, the median age was 30 years. Two had solitary lesions. Isodense lesions were found in 4 of 5 patients. PMID- 2584901 TI - Effect of caffeine on the bioavailability and pharmacokinetics of aspirin. AB - The objective of this study was to determine the influence of caffeine on aspirin bioavailability and pharmacokinetics in man. Two lots of the drugs were compared. The first lot (Lot # 1), which was caffeine-free, contained 650 mg aspirin plus 60 mg citric acid, whereas the second lot (Lot # 2) was caffeine-aspirin combination (650 mg aspirin plus 120 mg caffeine citrate, equivalent to 60 mg anhydrous caffeine). On two different occasions (2 weeks apart), the subjects received these two lots of drugs orally, i.e., each volunteer was given 650 mg aspirin (Lot # 1) or 650 mg aspirin plus 120 mg caffeine citrate (Lot # 2). It was found that caffeine significantly increased the rate of appearance as well as the maximum concentration of the salicylate in plasma by about 31 and 15 per cent, respectively. The area under the plasma concentration-time curve (AUC0 affinity) of salicylate was statistically higher in the subjects given the drug combination as compared to those given aspirin alone. Other pharmacokinetic parameters of the salicylate remained unchanged. It was therefore concluded that caffeine can increase the bioavailability of aspirin in man without any other effects on the salicylate disposition. PMID- 2584902 TI - Clinical assessment of respiratory impairment. AB - "Respiratory impairment" can be assessed roughly by clinical methods (symptom information and physical examination) and a simple bedside test ('match test'), and quantitatively and accurately by laboratory pulmonary function study (spirometry, arterial blood gas analysis and several other sophisticated tests). Whereas tests of respiratory impairment in a laboratory situation can predict dysfunction level reasonably well, a complete description of the function will depend in part on judgement, and in part on the motivation and attitude of the individual. Subject participation is an integral part of all evaluations. PMID- 2584903 TI - Hygienic status of food handlers. AB - The study demonstrated bacterial species on hands and nails of food-handlers before and after hand-washing. Those were Staphylococcus spp., Streptococcus spp., Micrococcus spp., Bacillus spp., Diphtheroid, Aeromonas hydrophila, Klebsiella pneumoniae, Acinetobacter, Enterobacter cloacae, Escherichia coli, Pseudomonas spp., Proteus mirabilis, Serratia spp., Citrobacter freundii. Before hand washing, each food-handler harboured one to eight bacterial species. After hand-washing (eight with water from plastic boxes, 97 from pipe water, 57 out of 97 (58.8%) used soap or detergent with water), disappearance of one to four bacterial strains from hands and nails were found in 47.6 per cent of food handlers. Cultures of water used for washing from eight plastic boxes yielded Staph. spp., Strep. spp., Aeromonas hydrophila, Kleb.pneumoniae, Acinetobacter anitratus, Enterobacter cloacae. From pipe water, Diphtheroid in 4, 4.1 per cent Micrococcus in 1, 1.03 per cent were shown. Comparing bacterial species found in food-handlers with long nails and short nails, 4-8 more species were revealed in the former than the latter for 35.7 per cent. After hand-washing, there was recontamination of bacterial species in 17 food-handlers. This was probably due to dirty napkins or dresses during hand-drying or from water in plastic boxes. PMID- 2584904 TI - Several sporadic outbreaks of El Tor cholera in Sunpathong, Chiang Mai, September October, 1987. AB - From September through October 1987, a cholera outbreak involving 59 cases of biotype El Tor, serotype Inaba occurred in Sunpathong district, Chiang Mai. No cases died. Twenty-seven cases were males and 32 were females. The age ranged between 4 months and 85 years, with a median of 36 years. The outbreak affected 7 small communities, and showed different vehicles of infection. Six housewives and one girl were infected with cholera in the first localized outbreak. The transmission of infection appeared due to the consumption of packed food contaminated by an infected food handler. In the second localized outbreak, 6 young males acquired cholera after eating uncooked fish harvested from a canal contaminated with cholera organisms. Another outbreak of cholera with 24 culture confirmed cases occurred among guests at a funeral held in one rural village. The source of infection was traced to uncooked pork contaminated from an infected butcher: Early detection of infected persons, rapid identification of possible vehicles of transmission, and prompt implementation of control measures effectively curtailed the extension of these outbreaks. PMID- 2584905 TI - Retroperitoneal malignant schwannoma: a case report. AB - Malignant Schwannoma is a primary nerve sheath tumor that rarely occurs within the retroperitoneum. It occurs more commonly in patients with von Recklinghausen's disease but is also seen without this association. Our patient demonstrated no evidence of multiple neurofibromatosis, as seen in classical von Recklinghausen's disease. A review of the English literature on retroperitoneal malignant schwannoma suggested that radical surgical excision offered the best hope for cure. Experiences with adjunctive chemotherapy and radiotherapy were too meagre for meaningful evaluation of their effectiveness. PMID- 2584907 TI - Retinal detachment in toxemia of pregnancy. AB - A case of exudative retinal detachment in a 16-year-old Thai woman with toxemia of pregnancy was reported. The patient developed bilateral retinal detachment during toxemia of pregnancy. After termination of pregnancy, the blood pressure returned to normal level, the subretinal fluid reabsorbed and the retina reattached. The visual acuity improved from 6/60 to 6/9 both eyes. PMID- 2584906 TI - Severe cases of green pit viper snake venom poisoning. AB - Two severe cases of green pit viper bites were reported. The clinical manifestations were severe bleeding and diarrhea. The first patient had acute renal failure complicated from severe diarrhea and hypovolemia. Hematological findings showed hypofibrinogenemia and thrombocytopenia. Renal biopsy performed in the first case showed a picture compatible with that of the recovery phase of acute tubular necrosis. Green pit viper antivenine serum together with symptomatic and supportive treatment was given. Both patients recovered uneventfully. PMID- 2584908 TI - Target materials suitable for projection X-ray microscope observation of biological samples. AB - Trials for improving the contrast of projection X-ray images by finding better target materials than Ti (lambda K alpha: 2.75 A), which has been found to be suitable for many kinds of specimens, were carried out, considering the factors of melting point, thermal conductivity, mechanical strength, chemical stability, absorption of the X-ray, etc. Au, Ta, and Ge were found to be suitable, giving 5 10 A X-rays when low electron beam energies around 10 kV were used. In order to take advantage of the long wavelength X-rays of these targets, we tried to minimize the attenuation of the imaging X-rays in the air or to use a vacuum camera. Even in non-stained biological samples such as HeLa cells and lingual muscle section, their microstructures were visible with sufficient contrast. PMID- 2584909 TI - Development of cellular polarity and tight junctions in parotid acinar cells of postnatal rat. AB - The morphogenesis of acino-tubular structures and cytodifferentiation of acinar cells in developing rat parotid glands from the day of birth to the 7th day after birth were studied by conventional ultrathin-section electron microscopy in conjunction with freeze replica and space tracer methods. An ultrathin-section study indicated that the acinar cells developed sequentially in the order of the following three stages: (1) the stage of undifferentiated cell immediately after birth, in which the presumptive acinar cells showed very scanty cell cytoplasm, poorly developed organellae, and no distinctive cellular polarity; (2) the stage about the 3rd day after birth, in which cells were arranged into a single layer, resulting in the establishment of three recognizable domains in the plasma membranes, and developing cellular organellae started to distribute with distinctive polarity; and (3) the stage of the 5th day after birth and thereafter, in which secretory granules were formed, indicating the beginning of exocrine functions. Freeze replica and a tracer study demonstrated that the formation of a sealing strand of tight junctional belt took place in correspondence to the establishment of cellular polarity. These results indicated that the development of cellular polarity, plasma membrane domains, tight junctions, and acino-tubular structure were closely interrelated to each other, and preceded the onset of secretory functions. PMID- 2584910 TI - Three-dimensional studies of cytoskeletal organizations in cultured thyroid cells by quick-freezing and deep-etching method. AB - Isolated porcine thyroid cells were cultured on collagen gels (control group, TSH stimulated group, and double-layered culture). They were split or cut to remove cytoplasmic soluble proteins for replica preparations. Some specimens were immunostained with anti-actin antibody or decorated with S1 myosin fragments to identify actin filaments. The basal cell membranes of thyroid cells of monolayer culture were in contact with collagen gels and the apical cell membranes faced the culture medium. Networks of actin filaments were attached to the cytoplasmic sides of the apical cell membranes, while intermediate filaments were localized along the basal ones. The thyroid-stimulating hormone (TSH) treatment induced the formation of microvilli only on the apical cell membranes and the accumulation of actin filaments under the apical cell membranes, indicating the apical-basal polarity of the cells. In double-layered culture, the primitive follicular lumens with microvilli appeared between two adjacent cells. The interaction of cell membranes with collagen gels is a determinant factor in the orientation of apical basal polarity. Moreover, the TSH treatment and cell-cell contact further intensify the polarization through reorganizing the cytoskeletons. PMID- 2584911 TI - Acetylcholine-induced activation of the eccrine sweat glands in a case of hypohidrotic congenital ectodermal dysplasia. AB - In a male patient suffering from congenital ectodermal dysplasia with sweating only on the plantar and palmar surface, we found that the anhidrotic eccrine sweat glands became able to produce sweat after repeated local application of acetylcholine. We ultrastructurally examined the sweat glands in skin biopsies before and after acetylcholine treatment. The secretory portion of the sweat glands of the right plantar region was characterized by well-developed basal infoldings and intercellular interdigitations, and also by dilated intercellular spaces and canaliculi. In the flexor region of the right brachium (anhidrotic area), the secretory portion showed hypoplastic features, especially denoted by the presence of few locally distributed basal infoldings and intercellular canaliculi. The secretory cells seemed to be hypofunctional with the nuclei containing much heterochromatin. After treatment, in the flexor region of the left brachium and the right infraclavicular region, where sweating was induced, the secretory portion appeared to be considerably activated, though hypoplastic structures were unchanged: the secretory cell nuclei contained dispersed chromatin, the Golgi apparatus in the dark cells was well developed, and both in the clear cells and the myoepithelial cells micropinocytotic vesicle-like structures increased in number. In ductular cells, mitochondria also increased in number. PMID- 2584912 TI - Distal surface of the rat ruffle-ended ameloblasts at the stage of enamel maturation observed by scanning electron microscopy. AB - Distal surface of the rat ruffle-ended ameloblasts was observed by high resolution scanning electron microscopy. Specimens fixed by perfusion with 0.5% formaldehyde and 0.5% glutaraldehyde were decalcified with ethylenediamine tetraacetic acid and freeze-fractured using dimethyl sulfoxide. They were treated with 0.1% osmium tetroxide for 96 hr to remove excess cytoplasmic matrices, dehydrated, and critical-point dried. The present method was useful for observing both surface and intracellular structures simultaneously. The dense lamina lining the distal surface of the ruffle-ended ameloblasts having been dissolved in this preparation, the surface was clearly demonstrated in three dimensions under SEM. The surface was characterized by a complex labyrinth formed by protrusion and invagination of the plasma membrane. At high magnification, two kinds of minute granules are visible: small and larger granules measured as 10-20 nm and 70 nm in diameter, respectively. The former were more numerous than the latter. Furthermore, microfibrils connecting the protrusions of the plasma membrane were observed on the distal surface. The small granules probably connect the dense lamina with the distal surface of the ameloblasts. In addition, a denuded area free from the granules was sometimes recognized on the distal surface. These surface structures of the distal end of the ameloblasts appeared to be concerned with the enamel maturation. PMID- 2584913 TI - Contrast as seen in visual search reaction times. AB - Three pigeons searched arrays of alphabetic letters displayed on computer monitors. On each trial, either an A or an E appeared, and the reaction time and accuracy with which the bird pecked at this target were measured. In each block of trials, each target (A or E) was displayed alone, or together with a number of distractor letters (2 or 18) that varied in their similarity to the target. During a baseline series of sessions, responses to the A and to the E each yielded food reinforcement on 10% of the trials. In the next series of sessions, reinforcement continued at 10% for A, but rose to 30% for E. In a final series, these reinforcement conditions were reversed. As expected, reaction times increased with target-distractor similarity and (for similar distractors) with the number of distractors. Increased reinforcement of E had no effect on reaction times to E, but produced a very consistent increase in reaction times to A; the average increase was constant across the various display conditions. Reversal of the differential reinforcement conditions reversed this contrast effect. Analysis of the reaction time distributions indicated that increased reinforcement to E decreased the momentary probability of response to A by a constant amount, regardless of display conditions. These results are discussed in relation to theories of contrast, memory, and of the search image. PMID- 2584914 TI - On the limits of the matching concept in monkeys (Cebus apella). AB - Two cebus monkeys, with many years of experience matching a variety of static visual stimuli (forms and colors) within a standard matching-to-sample paradigm, were trained to press a left lever when a pair of displayed static stimuli were the same and to press a right lever when they were different. After learning the same/different task, the monkeys were tested for transfer to dynamic visual stimuli (flashing versus steady green disks), with which they had no previous experience. Both failed to transfer to the dynamic stimuli. A third monkey, also with massive past experience matching static visual stimuli, was tested for transfer to the dynamic stimuli within our standard matching paradigm, and it, too, failed. All 3 subjects were unable to reach a moderate acquisition criterion despite as many as 52 sessions of training with the dynamic stimuli. These results provide further evidence that, in monkeys, the matching (or identity) concept has a very limited reach; they consequently do not support the view held by some theorists that an abstract matching concept based on physical similarity is a general endowment of animals. PMID- 2584916 TI - Instructional control of generalized relational matching to sample in children. AB - Three experiments examined the performance of 4-year-old children in matching geometric stimuli. Performance was developed as a simulation in which all components of the behavior were overt and directly measured. A correct match depended on the state of an instructional stimulus: the background color of the display. In the first two experiments, on nonidentity trials (signified by a green background) the next longer length, larger size, or greater distance was correct. With a blue background, a comparison identical to the sample was correct. In Experiment 3, red was added for which shorter, smaller, or nearer was correct. Also here, on nonidentity trials, if a comparison of the correct length was not presented, the children adjusted their search target to the comparison of the next succeeding size (larger or smaller) so as to maintain a constant matching relation. Subsequently, when exposure to the instructional stimulus was reduced to presentation only at the beginning of each trial, performance simulated matching based on instructions about abstract relations. In all experiments, accurate matching generalized across novel stimuli and reduced exposure to the instructional stimuli. PMID- 2584915 TI - Relational and absolute stimulus learning by monkeys in a memory task. AB - Three experiments showed stimulus control by either the absolute properties of probe stimuli, relational properties of the probe-list relationship, or both in a serial probe recognition memory task in which a four-item memory list was followed by a single probe (test) item. In Experiment 1, 3 rhesus monkeys received 39 to 75 repetitions of the same 24-trial stimulus sequence. Special tests showed stimulus control by the absolute properties of the probe stimuli. Retention of previous relational control was demonstrated by the good transfer (83%) to novel list and probe stimuli at the beginning of Experiment 2. During Experiment 2, control by absolute properties of the probe stimuli gradually reoccurred. Only a small measure of control by list stimuli could be detected or promoted. In Experiment 3, 4 monkeys were shown to have largely lost their ability to perform on the basis of the list-probe relationship, and were performing primarily on the basis of the absolute properties of the probe stimuli. Over the next 15 weeks, these monkeys were transferred to new stimuli at the beginning of each week. Control by the relational aspects of the task gradually returned. As transfer performance increased, control by the absolute properties of the probe stimuli was eliminated. The results are discussed in terms of stimulus control and performance strategies used by the monkeys. PMID- 2584917 TI - Short-term memory for responses: the "choose-small" effect. AB - Pigeons' short-term memory for fixed-ratio requirements was assessed using a delayed symbolic matching-to-sample procedure. Different choices were reinforced after fixed-ratio 10 and fixed-ratio 40 requirements, and delays of 0, 5, or 20 s were sometimes placed between sample ratios and choice. All birds made disproportionate numbers of responses to the small-ratio choice alternative when delays were interposed between ratios and choice, and this bias increased as a function of delay. Preference for the small fixed-ratio alternative was also observed on "no-sample" trials, during which the choice alternatives were presented without a prior sample ratio. This "choose-small" bias is analogous to results obtained by Spetch and Wilkie (1983) with event duration as the discriminative stimulus. The choose-small bias was attenuated when the houselight was turned on during delays, but overall accuracy was not influenced systematically by the houselight manipulation. PMID- 2584918 TI - Preference for starting and finishing behavior patterns. AB - Pigeon's key pecking was reinforced with food in two experiments in which the correspondence between preference for starting one of two reinforced behavior patterns and the likelihood of finishing it subsequently was examined. Reinforcers were scheduled according to concurrent schedules for two classes of interresponse times, modified such that reinforcers followed a center-key peck terminating either a shorter interresponse time started by a left-key peck or a longer interresponse time started by a right-key peck. In Experiment 1, the times when reinforcers potentially were available were not discriminated, whereas in Experiment 2 they were. Absolute reinforced pattern durations were varied. The relative frequency of starting a particular pattern was highly correlated with relative frequency of that completed pattern in both experiments. Other relations between starting and finishing a pattern depended on whether reinforced interresponse times were discriminated. For instance, preference for starting a pattern sometimes correlated negatively with the likelihood of subsequently completing it. The present experiments are described as capturing part of the ordinary language meaning of "intention," according to which an organism's behavior at one moment sets the occasion for an observer to say that the organism "intends" in the future to engage in one behavior rather than another. PMID- 2584919 TI - Global increase in response latencies by early middle age: complexity effects in individual performances. AB - Ten young women (age 20 to 22 years) and 10 middle-aged women (age 36 to 44 years) served as subjects in choice reaction time, letter classification, and abstract matching-to-sample tasks. In each of seven conditions, the older group responded more slowly than the younger group. Age differences showed a complexity effect. That is, differences between the latencies of young and old subjects increased as the latency of the young subjects increased. Both linear and power functions accurately described the relation between the latencies of the middle aged and young adult groups. This was true not only for the relation between average latencies but also for the relation between corresponding quartiles of latency distributions. Similar results were observed at the individual level: All middle-aged subjects showed complexity effects, and, for each middle-aged subject, the relation between her latencies and those of the average young adult was well described by linear and power functions. These findings indicate that age-related slowing is apparent by age 40, and that complexity effects are observable in individual performances. This slowing is global and not specific to particular tasks, as indicated by the fact that the latencies of older adults can be predicted directly from those of younger adults without regard to the nature of the task. PMID- 2584920 TI - An ecological analysis of knowing by wielding. AB - The ecological approach to perception, as developed by James Gibson, is described and applied to how one knows, by means of the haptic perceptual system, various properties of hand-held objects. Four sets of experiments are reviewed in which subjects reported on the extent, orientation, shape, and fractional components of unseen objects wielded freely. For each task, an invariant specific to the object property in question is identified in the structured arrays of rotational moments and strains produced by the act of wielding. Results are discussed in relation to the concepts of attention and stimulation, as reformulated by the ecological approach, and the general theory of perception as information pickup. PMID- 2584921 TI - Mechanisms of attention: a developmental study. AB - A model of selective attention is proposed which contains a number of properties. First, stimuli which are irrelevant to the subjects' task can be analyzed to semantic levels automatically, and such stimuli can produce intrusion/interference effects. Second, two mechanisms by which selection is achieved are habituation to, and inhibition of, these irrelevant stimuli. A series of studies demonstrates that both the ability to process automatically irrelevant stimuli and the habituation mechanisms of attention are observable by Grade 2, whereas the inhibitory mechanism is not always evident at this stage. It is suggested that the greater distractability of children in certain situations may be due in part to the underutilization of this inhibitory mechanism. We further propose that children may be able to employ inhibitory mechanisms in more familiar perceptual-motor tasks. PMID- 2584922 TI - Complementary versus contrastive classification in preschool children. PMID- 2584923 TI - Picture versus question elaboration on young children's learning of sentences containing high- and low-probability content. AB - The main purpose of the two experiments reported here was to compare the potency of two types of elaboration on children's learning of sentence content: The effects of partial picture adjuncts were compared to the effects produced by answering "why"-questions about the relationships specified in the sentences. Five- to seven-year-old children heard sentences of the form, subject/verb/direct object/preposition/instrument. Sentences contained either a high-probability or a low-probability instrument given the semantic context. In Experiment 1, sentences either were accompanied by a partial picture depicting the sentence action but omitting the instrument or were presented without a partial picture accompaniment. Recall was improved by provision of partial pictures at study. In Experiment 2, the sentences were accompanied by complete pictures depicting the sentence content. In both experiments, questioning significantly reduced recall of high-probability sentences, with recall of instruments affected especially negatively. Evidence is presented that insufficient attention to instruments may have been one mechanism mediating depressed recall of high- compared to low probability instruments in the questioned conditions. In summary, partial pictures improved cued recall of sentences in this study; in contrast, all significant effects produced by answering why-questions were negative ones (i.e., later recall was reduced following interrogation at study). PMID- 2584924 TI - A peptide binding protein having a role in antigen presentation is a member of the HSP70 heat shock family. AB - The T cell recognition of globular protein antigens requires the processing and presentation of the antigen by Ia-expressing APCs. Processing is believed to involve the uptake of antigen into an acidic compartment where proteolysis occurs. The resulting peptides containing the T cell antigenic determinant are associated with Ia and presented at the cell surface to the specific T cells. The mechanisms by which antigenic peptides become associated with Ia is not known. We previously described a peptide binding protein of 72/74 x 10(3) Mr (PBP72/74) that plays a role in antigen presentation as shown by the ability of an antiserum raised in rabbits to affinity-purified PBP72/74 to block presentation of cytochrome c to a cytochrome c-specific T cell hybrid. Here we show that PBP72/74 is recognized by mAbs specific for members of the HSP70 family of proteins. In Western blots PBP72/74 is bound by mAb 7.10, specific for an evolutionarily conserved epitope of HSP proteins and by mAb N27, specific for both the constitutively expressed and inducible 72/73 x 10(3) Mr HSP70 proteins. In addition, PBP72/74 shares a second common feature of the HSP proteins, that of binding to ATP. Indeed, ATP causes the release of PBP72/74 from binding to a peptide fragment of cytochrome c (Pc 81-104) and PBP72/74 can be eluted from ATP columns by Pc 81-104. Finally, a portion of PBP72/74 is shown to be present on B cell surfaces by immunofluorescence staining. Thus, it appears that characteristics of the heat shock proteins are shared by a protein playing a role in antigen presentation, suggesting some commonality in function. PMID- 2584925 TI - Analysis of a novel VHS107 haplotype in CLA-2 and WSA mice. Evidence for gene conversion among IgVH genes in outbred populations. AB - Gene conversion has been suggested as the basis for many VH allelic differences, particularly in the murine VHS107 family. Whether conversion among IgVH genes is likely to have occurred in outbred populations has not been directly addressed. The CLA-2/Cn and WSA strains, which were recently and independently derived from a feral population exhibiting low responsiveness to PC, provide the opportunity to approach this question. In previous studies, the heavy chain cDNA sequence of a PC-specific hybridoma derived from CLA-2/Cn suggested gene conversion events within the VHS107 family. Accordingly, we have examined the germline VHS107 genes of CLA-2/Cn and WSA. The results indicate that: (a) The CLA-2 and WSA strains bear an identical but novel VHS107 family haplotype, which lacks a V3 element and contains a V1, a V13, and two V11 genes; (b) low PC responsiveness in these populations is unlikely due to an inability to express the V1 member of the VHS107 gene family; and (c) when compared with the other known VHS107 haplotypes, the proportion of differences consistent with gene conversion greatly exceeds that expected by random base substitution. Thus, gene conversion events appear to have occurred with considerable frequency in the evolution of the murine VHS107 family, especially among the V3, V13, and V11 members. PMID- 2584926 TI - I-E-linked control of spontaneous rheumatoid factor production in normal mice. AB - The concentration of serum IgM molecules binding to IgG2a (rheumatoid factor [RF]) in solid phase assays is 10-100-fold higher in normal, unmanipulated C3H/HeJ (H-2k) than in C57BL/6 (H-2b) mice. Analysis of MHC-congenic mice with the prototype strains show that C3H SW (H-2b) are low, and B6.H-2k are high RF expressor strains, respectively. Furthermore, segregation of RF phenotypes in progenies from backcrosses to C3H/HeJ of (C3H/HeJ x C57BL/6)F1 hybrid mice shows MHC- and IgH-linked controls. RF phenotypes also segregate as if they are MHC linked in crosses between H-2-congenic strains (C3H/HeJ and C3H.SW). The study of intra-H-2 (k/b and k/s) recombinant mice suggested that RF phenotype control is linked to the I-E region. This was confirmed by the typing of C57BL/6 mice expressing a transgenic E alpha chain, and thus, I-E+, which, in contrast to nontransgenic littermates, are high expressors of RF. PMID- 2584928 TI - Local production of tumor necrosis factor alpha, interleukin 1, and interleukin 6 in meningococcal meningitis. Relation to the inflammatory response. AB - We examined the cerebrospinal fluid (CF) taken on admission from 60 patients with infections caused by Neisseria meningitidis for presence of TNF-alpha, IL-1, and IL-6. TNF-alpha was detected in CF in 55 and 19% (p = 0.03), IL-1 in 50 and 15% (p = 0.05), and IL-6 in 98 and 100% of patients with meningitis and septic shock/bacteremia, respectively. The median IL-6 concentration in CF in patients with meningitis was 154 ng/ml, and in patients with septic shock/bacteremia it was 42 ng/ml (p = 0.001). The level of LPS in CF correlated with the level of TNF alpha (r = 0.91, p less than 0.001), but not with the level of IL-1 and IL-6. CF levels of TNF-alpha, IL-1, and IL-6 correlated with each other (r = 0.34-0.54, p less than 0.01), with the protein concentration (r = 0.34-0.62, p less than 0.01) and inversely with the CF/blood glucose ratio (r = -0.34 to -0.67, p less than 0.01). Only the Il-6 level correlated with the leukocyte count (r = 0.37, p less than 0.01). In rabbits TNF-alpha, IL-1, and IL-6 activities sequentially appeared in CF within 3 h of injection of meningococcal LPS or viable meningococci, whereas the main infiltration of granulocytes started after 4 h. TNF-alpha was detected in serum at concentrations less than 1/100 of those in CF after administration of LPS into the subarachnoid space, and conversely, TNF-alpha was detected in CF at concentrations 1/100 of those in serum after intravenous injection of LPS. The results demonstrate that TNF-alpha, IL-1, and IL-6 are sequentially produced in the initial phase of the local inflammatory response caused by meningococci, and that the subarachnoid space and systemic circulation are separate compartments with respect to production of TNF-alpha, IL-1, and IL 6. PMID- 2584927 TI - Comparison of exon 5 sequences from 35 class I genes of the BALB/c mouse. AB - DNA sequences of the fifth exon, which encodes the transmembrane domain, were determined for the BALB/c mouse class I MHC genes and used to study the relationships between them. Based on nucleotide sequence similarity, the exon 5 sequences can be divided into seven groups. Although most members within each group are at least 80% similar to each other, comparison between groups reveals that the groups share little similarity. However, in spite of the extensive variation of the fifth exon sequences, analysis of their predicted amino acid translations reveals that only four class I gene fifth exons have frameshifts or stop codons that terminate their translation and prevent them from encoding a domain that is both hydrophobic and long enough to span a lipid bilayer. Exactly 27 of the remaining fifth exons could encode a domain that is similar to those of the transplantation antigens in that it consists of a proline-rich connecting peptide, a transmembrane segment, and a cytoplasmic portion with membrane anchoring basic residues. The conservation of this motif in the majority of the fifth exon translations in spite of extensive variation suggests that selective pressure exists for these exons to maintain their ability to encode a functional transmembrane domain, raising the possibility that many of the nonclassical class I genes encode functionally important products. PMID- 2584929 TI - Prevention of endogenous leukotriene production during anaphylaxis in the guinea pig by an inhibitor of leukotriene biosynthesis (MK-886) but not by dexamethasone. AB - Leukotriene C4 (LTC4) underwent rapid elimination from the circulating blood and was extensively converted to LTD4 within the vascular space of the guinea pig. To mimic the elimination and metabolism of endogenous LTC4 generated during anaphylaxis, 14,15-3H-labeled LTC4 was infused intravenously over a period of 15 min, leading to a recovery in bile of 85% of the infused LT radioactivity within 2 h. Corresponding to the tracer studies, LTD4 and, to a lesser extent, LTC4 were the predominant endogenous cysteinyl LTs in guinea pig bile. The biliary production rate of endogenous LTD4 increased from 0.3 +/- 0.1 to 6.2 +/- 1.8 pmol x min-1 x kg-1 (p less than 0.001) during anaphylactic shock induced by intravenous injection of OVA (0.2 mg/kg) into sensitized guinea pigs. A novel LT biosynthesis inhibitor (MK-886; 10 mg/kg, i.v., 15 min before antigen challenge) suppressed the antigen-induced cysteinyl LT production by greater than 92% (p less than 0.001). This inhibition of systemic LTC4 formation was associated with a complete protection against lethal anaphylactic shock in animals pretreated in addition with the H1 receptor antagonist pyrilamine. Pretreatment with either the inhibitor of LT synthesis or the histamine receptor antagonist reduced the lethality during anaphylactic shock from 100 to 60 and 78%, respectively. In artificially ventilated, pyrilamine-pretreated animals, the antigen-induced decrease in dynamic lung compliance and the rise in hematocrit were significantly reduced (p less than 0.05) by pretreatment with the inhibitor of LT synthesis. Dexamethasone at high doses (10 mg/kg, i.p., once daily for 7 d, or in a single dose of 10 mg/kg, i.v., 3.5 h before challenge) had no inhibitory effect on LT generation during anaphylaxis in vivo. However, in resident peritoneal macrophages, harvested from these dexamethasone-treated sensitized guinea pigs and stimulated with zymosan, both cysteinyl LT and 6-keto-PGF1 alpha formation were strongly suppressed. These studies indicate an important role of cysteinyl LTs in systemic anaphylaxis in vivo and demonstrate the blockade of anaphylactic LT generation by a novel inhibitor of LT biosynthesis (MK-886) but not by dexamethasone. PMID- 2584930 TI - Generation of biliary lesions after transfer of human lymphocytes into severe combined immunodeficient (SCID) mice. AB - Human PBL have been reported to reconstitute B and T cells as well as human serum Ig in mice with severe combined immunodeficiency disease (SCID). To confirm these observations and attempt the transfer of an autoimmune disease to the immunodeficient animals, groups of SCID mice received an injection of PBL from patients with primary biliary cirrhosis (PBC) or from normal volunteers. By 8 wk after the injection of 10-42 x 10(6) PBL into the mice, human lymphoid cells were detected in the spleen of approximately half of the animals and all had detectable serum levels of human IgG. Moreover, the sera of SCID mice that received cells from patients with PBC contained human antimitochondrial antibodies (AMA) to dihydrolipoamide acetyltransferase, the major mitochondrial autoantigen of PBC. Histologically, a human mononuclear cell infiltrate was present around the portal areas of the liver and inflammation, bile duct atypica, and necrosis of bile duct cells were observed. While the biliary lesions in the SCID recipients of PBC cells were more severe, a mononuclear infiltrate was clearly evident in mice that received cells from normal donors, suggesting the presence of a graft-vs.-host-like disease. While these data are the first to describe an animal model with both the humoral and cellular characteristics of PBC, they also raise an interesting question regarding the preferential localization of lymphoid cells to the biliary system. PMID- 2584931 TI - The Mac-2 antigen is a galactose-specific lectin that binds IgE. AB - A cDNA encoding the Mac-2 antigen, a surface marker highly expressed by thioglycollate-elicited macrophages, has been cloned by immunoscreening of a lambda gt11-P388D1 expression library. The nucleotide sequence of the cDNA is identical to that of carbohydrate-binding protein 35, a galactose-specific lectin found in fibroblasts and highly homologous to a rat IgE-binding protein from basophilic leukemia cells. The in vitro synthesized Mac-2 protein displayed the expected carbohydrate- and IgE-binding properties. By pulse-chase analysis and subcellular fractionation studies, the Mac-2 protein was found in the cytosol but was also seen to accumulate in the extracellular medium. The latter finding was surprising in view of the fact that the cDNA did not encode a signal peptide or transmembrane domain. An alternatively spliced cDNA with the potential to encode a NH2 terminally extended Mac-2 protein with a stretch of hydrophobic amino acids at its NH2 terminus was also found, but it is not clear whether it is the source of the extracellular Mac-2. Possible functions for the Mac-2 protein based on its lectin- and IgE-binding properties are discussed. PMID- 2584932 TI - One synchronous wave of B cell development in mouse fetal liver changes at day 16 of gestation from dependence to independence of a stromal cell environment. AB - Precursor cells of the B lineage can be enriched from mouse fetal liver by FACS with the aid of the pre-B cell-specific mAb G-5-2. The cells are concomitantly enriched for cells expressing the pre-B cell-specific gene lambda 5, and for cells developing to LPS-reactive mature B cells. The enriched purified precursors are not influenced by rIL-2 through -7, alone or in combination, to develop to mitogen-reactive, sIg+ cells. Marginal proliferation of the precursors is observed in response to IL-3 plus -4, and IL-6 plus -7, and this does not change in the presence of stromal cells. Development to mitogen-reactive, sIg+ cells is dependent on interactions with embryonic stromal cells from fetal liver. Two mAbs raised against the stromal cells inhibit this development. Two phases of precursor cell development can be distinguished in fetal liver. Between days 13 and 15 of gestation, it is dependent on stromal cell interactions, thereafter, from days 16 to 19, it is independent. A sudden increase in the number of mitogen reactive, sIg+ B lineage cells occurs within 24 h between days 16 and 17. All these results indicate that B cell development occurs in one wave with synchronous steps of changes from a mitogen-insensitive, sIg-, stromal cell dependent to a mitogen-reactive, sIg+, stromal cell-independent B lineage line. PMID- 2584933 TI - The staphylococcal toxic shock syndrome toxin 1 triggers B cell proliferation and differentiation via major histocompatibility complex-unrestricted cognate T/B cell interaction. AB - The Staphylococcus aureus exotoxin toxic shock syndrome toxin 1 (TSST-1) is a potent activator of T cells and monocytes. We have recently demonstrated that TSST-1 is a superantigen that binds monomorphic determinants on MHC class II molecules. In the present study, we have examined the effect of TSST-1 on the activation and differentiation of high density human tonsillar B cells. TSST-1 bound to tonsilar B cells with high affinity and saturation kinetics. This binding was effectively inhibited by a combination of anti-HLA-DR and anti-HLA-DQ mAbs. Treatment of purified B cells with TSST-1 failed to induce B cell proliferation or Ig production. However, in the presence of irradiated T cells, TSST-1 induced resting B cells to proliferate and differentiate into Ig secretory cells. TSST-1 mimicked nominal antigen in that its induction of B cell responses was strictly dependent on physical contact between T and B cells, and was profoundly inhibited by anti-MHC class II mAbs, anti-CD3 mAbs, and, to a lesser extent, by anti-CD18 mAbs. However, unlike nominal antigen, TSST-1-mediated T/B cell interactions were MHC unrestricted. These results suggest that TSST-1 induces T cell-dependent B cell proliferation and differentiation by virtue of its ability to mediate MHC-unrestricted cognate T/B cell interaction via the TCR/CD3 complex and MHC class II antigens. PMID- 2584934 TI - Evidence of eosinophil granule major basic protein in human placenta. AB - A protein immunochemically related to the eosinophil granule major basic protein (gMBP) is found in increased concentration in the plasma of pregnant women and has been localized to placental trophoblasts by immunofluorescence. Pregnancy MBP (pMBP) is indistinguishable from gMBP in its reactivity with polyclonal antisera and a panel of 14 mouse mAbs. We report the purification of pMBP from human placenta by: (a) affinity chromatography over mAb immobilized on Sepharose, (b) gel filtration in 6 M guanidine.HCl buffer, and (c) reversed-phase HPLC. Purified pMBP and gMBP are biochemically indistinguishable in that both: (a) bind to DNA, (b) polymerize and bind to carrier proteins via disulfide linkages, (c) have a molecular weight of 14,000, (d) have isoelectric points greater than 10.6, (e) comigrate in two-dimensional gels, (f) coelute during reversed-phase HPLC on C18 columns, (g) have identical peptide maps after three different digestions, and (h) have partial amino acid sequence identity. This physicochemical identity has important implications as to the role of pMBP in human placentation. PMID- 2584935 TI - The major parasite surface antigen associated with human resistance to schistosomiasis is a 37-kD glyceraldehyde-3P-dehydrogenase. AB - Schistosomiasis, due to Schistosoma mansoni, is a major health problem in many subtropical countries, and major efforts are being made to define a vaccine. In this regard, we have reported that sera from subjects with low susceptibility to infection by S. mansoni react with a major larval surface antigen (P-37), having an apparent molecular mass of 37 kD, against which sera of susceptible individuals show little reactivity. We have now cloned the cDNA for this antigen by screening a schistosome cDNA expression library with antibodies against the purified protein. The selected cDNAs encode a protein that is specifically identified by immune human sera containing antibodies against P-37, while sera exhibiting low or no reactivity toward P-37 fail to recognize the recombinant protein. The cloned cDNAs hybridize with a 1.2-kb RNA that is the transcript of a single copy gene. This RNA directs the synthesis of a 36.5-kD polypeptide that is precipitated by sera from the most resistant subjects. The amino acid sequence of the encoded polypeptide shows homology with the glycolytic enzyme Glyceraldehyde 3P-dehydrogenase (72.5% of positional identity with human Glyceraldehyde-3P dehydrogenase). Antibodies against the recombinant protein identified P-37 on the larva. These findings, together with other reports, indicate that a number of conserved proteins may be major targets of host-protective immunity against S. mansoni. The hypothesis is discussed that genetic restriction of the immune response to these antigens may occur in heterogeneous human populations because of the limited number of T cell epitopes carried by these host-like proteins. Such genetic effects might allow parasite transmission through nonresponder (susceptible) individuals. This hypothesis and the protective properties of P-37 can now be tested using the recombinant protein and synthetic peptides derived from selected regions of the polypeptide chain. PMID- 2584936 TI - Tumor necrosis factor plays a protective role in experimental murine cutaneous leishmaniasis. AB - The ability of mice to resist infection with L. major correlated directly with the capacity of their LNC to produce TNF in response to in vitro parasite challenge. Blocking TNF in vivo by passively administering anti-TNF antibodies exacerbated the course of L. major infection, resulting in substantially larger cutaneous lesions and elevated numbers of parasites within those lesions. In addition, treatment of infected mice with exogenous rHuTNF afforded host protection as evidenced by smaller lesion size and decreased parasite counts. Taken together, these results suggest a central role for TNF in resistance to L. major. PMID- 2584938 TI - The immunogenicity of chimeric antibodies. AB - Mice were immunized with model xenogeneic (both the VH frameworks and the CH domains of human origin), chimeric (just VH frameworks human), or self antibodies, and the antiantibody responses were dissected. Only the self antibody did not elicit a response. A strong response was elicited by the most xenogeneic antibody with approximately 90% against the C and approximately 10% against the V. The anti-V response was not attenuated in the chimeric antibody, demonstrating that foreign VH frameworks can be sufficient to lead to a strong antiantibody response. The magnitude of this xenogeneic anti-VH response was similar to that of the allotypic response elicited by immunizing mice of the Igha allotype with an Ighb antibody. Thus, although chimerization can diminish antiantibody responses, attention should be paid both to V region immunogenicity and to polymorphism. PMID- 2584939 TI - Discussion of "Repetitive Deoxyribonucleic Acid (DNA) and Human Genome Variation- A Concise Review Relevant to Forensic Biology". PMID- 2584940 TI - Inactivation of human immunodeficiency virus (HIV) by ionizing radiation in body fluids and serological evidence. AB - A method to use ionizing radiation to inactivate HIV (Human Immunodeficiency Virus) in human body fluids was studied in an effort to reduce the risk of accidental infection to forensic science laboratory workers. Experiments conducted indicate that an X-ray absorbed dose of 25 krad was required to completely inactivate HIV. This does not alter forensically important constituents such as enzymes and proteins in body fluids. This method of inactivation of HIV cannot be used on body fluids which will be subjected to deoxyribonucleic acid (DNA) typing. PMID- 2584941 TI - Biostatistical evaluation of evidence from continuous allele frequency distribution deoxyribonucleic acid (DNA) probes in reference to disputed paternity and identity. AB - We present a development and discussion of the biostatistical evaluation of deoxyribonucleic acid (DNA) probe evidence in forensic science cases of disputed paternity and identity. We restrict ourselves to single-locus codominant systems (highly analogous to more conventional systems) which have the apparently novel complication of an experimentally continuous allele frequency distribution. This complication necessitates reformulations of standard biostatistical summaries of the evidence (the paternity index (PI) and the phenotype frequency, respectively). These reformulations, rather than representing a unique case, have applicability to the evaluation of evidence obtained in standard genetic systems now in widespread use. PMID- 2584937 TI - Perforin and serine esterase gene expression in stimulated human T cells. Kinetics, mitogen requirements, and effects of cyclosporin A. AB - A pore-forming protein (PFP; perforin) and various serine esterases (SE) have been identified in the cytoplasmic granules of CTL and NK cells. Perforin and several SE have recently been cloned. Northern blotting analysis was performed here using cDNA probes specific for human perforin and two SE (SE 1/HS and SE 2/GB) to monitor the levels of specific mRNAs in mitogen-stimulated primary human T cells. These mRNAs were rapidly induced by IL-2 with optimal responses at 300 U/ml. After IL-2 treatment, mRNAs for perforin, SE 1, and SE 2 peaked at 12-24 h and decreased after 48 h. The three mRNAs were also induced in T cells treated with a combination of PMA plus lectin, OKT3 mAb, or plastic-adherent accessory cells. However, the induction induced by PMA/mitogen followed a slower kinetics, peaking at 48 h. In general, we found that SE 1 mRNA was more readily induced by IL-2, while SE 2 responded better to PMA/mitogen. Similar patterns of mRNA expression were observed for both unprimed T cells and PHA-primed T blasts. After stimulation with IL-2 and PMA/mitogen, the T8+ subset was shown to be the main producer of perforin, SE 1, and SE 2. Low levels of all three mRNAs, however, were also detected in the T4+ subset. The induction of all three mRNAs by either IL-2 or PMA/mitogen was partially blocked by the immunosuppressive drug cyclosporin A (CsA), but not by the biologically inactive analogue cyclosporin H. Together, these results point to some similarities and differences with upregulation of granule mediator mRNAs relative to lymphokine mRNAs. Both sets of genes require two signals for their induction by mitogens. In contrast to lymphokines, there is a strong response of granule mRNAs to IL-2, and the induction of these transcripts is only partially blocked by CsA. PMID- 2584942 TI - Group specific component: isoelectric focusing subtyping and immunoblot detection. AB - A method for the detection of group specific component (Gc) by immunoblotting, following isoelectric focusing (IEF), is described. This isoelectric focusing method resolves the six common phenotypes of Gc using a narrow range pH 4.5 to 5.4 ampholyte. The Gc proteins were passively transferred from the IEF gel to nitrocellulose and detected with goat anti-Gc followed by peroxidase labeled anti goat immunoglobulin (Ig) antibody. The increased sensitivity of this technique results in the typing of stains older than one year and also those stains with minimal concentrations of the Gc protein. The polyacrylamide gel can also be used for the subtyping of esterase D. PMID- 2584943 TI - A study on the standard for forensic anthropologic identification of skull-image superimposition. AB - By means of X-ray photography tests were made of 224 (100 males and 124 females) volunteer Chinese adults of Han nationality to study the related regular patterns of superimposed projection of face landmarks onto the skull. On the basis of these tests, the present article reveals from a forensic anthropology angle the related regular patterns of plane projection of the human face with its skull. Study shows that there exist a strict individual identity and exclusiveness in relation between the human face and skull. The related regularity of displacement of face landmarks appears in projection of the skull with the human head at different photographic positions and angles. On the basis of this discovery, 52 indexes in 4 groups were established as a standard for judging the identification of a skull's body origin by means of skull-image superimposition. Based on forensic anthropology, the technique has raised to a great extent the credibility of unknown skull identification. In the past 8 years, 89 unknown skulls have been identified with their body origins which provided important and accurate evidence for the solution of murders with dismembered bodies, skeletonized bodies, and unidentified dead bodies. PMID- 2584945 TI - Unexpected death as a result of infective endocarditis. AB - Thirteen cases of infective endocarditis (IE) diagnosed for the first time at autopsy or, in those patients with a previous diagnosis of IE, not thought to be active at the time of death, are presented. Of the six patients who died within 24 h of the onset of symptoms, two died of obstruction of a valve orifice, two died of sepsis, one died of sepsis and alcoholic cardiomyopathy, and one died of a coronary artery embolus. Of the five patients with symptoms lasting more than 24 h, three died of sepsis and congestive heart failure. One died from sepsis alone and one died from congestive heart failure (CHF). In two patients whose duration of symptoms is unknown, one died of sepsis and CHF, and in the other the mechanism of death is unknown. Predisposing factors present in 11 of 13 patients included alcoholism (three), intravenous (IV) drug abuse (three), prosthetic valves (three), aortic stenosis (two), past rheumatic fever (one), and nonstenotic congenitally bicuspid valves (two). The reasons for no antemortem diagnosis were a missed or incorrect clinical diagnosis in three patients seen by a physician shortly before death, no signs or symptoms or found dead (four), non specific signs and symptoms (three), refusal of medical treatment (one), and a solitary lifestyle (one); there was insufficient information about one patient. Individuals with needle tracks, generalized petechiae. Osler's nodes, splinter hemorrhages, intravenous catheters, pacemaker wires, and infected aortic-valve (A V) shunts are at risk of IE. Blood and the vegetations should be cultured. The attending physician should be notified of the diagnosis in such cases. PMID- 2584944 TI - Dental characteristics of a large military population useful for identification. AB - The number and complexity of dental restorations has decreased for younger Americans. Since the presence and extent of restorations are important data for forensic science identification purposes, the Computer-Assisted Postmortem Identification (CAPMI) system was used to assess the practical effect of the decreased selectivity expected as a result of improved dental health. Dental examination data from 7030 soldiers were recorded on optical mark read forms and entered into a database. The data were reorganized and analyzed to generate summary statistics about the incidence of each type of restoration (divided into 16 categories) for both anterior, posterior, upper, lower, and combined segments. Patients' ages ranged from 17 to 49 with a mean of 24 years 5 months. Sixty percent were from 18 to 25 years old. A characteristic is defined as any situation other than a virgin tooth; for example, extracted, missing, unerupted, or restored. The average subject had 7 dental characteristics with approximately 75% having 4 or more. Within the entire population, 9% had 32 unrestored teeth. 3.6% had only one characteristic. To test the selectivity and uniqueness of various combinations of dental characteristics, 363 simulations using the CAPMI system were made against the entire 7030 subject database. Sample records (33 per group) with 2, 3, 4, 5, 6, 7, 8, 9-11, 12-14, 15-18, and 19+ characteristics were chosen at random from the database and searches were made.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2584946 TI - Fatal accidental enflurane intoxication. AB - Among reported cases of abuse of volatile anesthetics there is only one of enflurane intoxication. We report another fatal enflurane intoxication. A 21-year old man found dead seemed to have experimented with enflurane. Three and one-half days after death high amounts of enflurane were detected in blood, brain, and subcutaneous fat. Gas chromatographic quantification revealed the following high enflurane concentrations: blood: 130 mg/l-1, brain: 350 mg/l-1, and subcutaneous fat: 100 mg/l-1. Histologic signs of drug-induced damage were lacking. No suicide intentions became known. It was concluded that the young man died of an accidental intoxication while abusing enflurane. PMID- 2584947 TI - Carbofuran poisoning of pregnant woman and fetus per ingestion. AB - A case of carbamate pesticide poisoning of a pregnant woman by carbofuran ingestion is presented. The mother recovered from the poisoning in the hospital but necrosis of the fetus was found. Toxicological findings of the liver, brain, and kidney of the fetus revealed carbofuran in concentrations comparable with the mother's blood. Our findings in the case contribute to the research on permeation of the placental barrier by chemical substances. PMID- 2584948 TI - Phenotyping of alpha-2-HS glycoprotein in bloodstains by isoelectric focusing and immunoblotting. AB - A sensitive immunoblotting procedure has been applied to the detection of alpha-2 HS-glycoprotein (A2HS) phenotypes from control and casework bloodstains. A2HS phenotypes were separated by thin layer polyacrylamide gel isoelectric focusing (PAGIEF) in gels containing Pharmalyte pH 4.2-4.9. After transfer to nitrocellulose by a rapid capillary blot, the A2HS phenotypes were developed using a double antibody enzyme-immunoassay. The evaluation of A2HS phenotyping of casework material was undertaken in parallel with phosphoglucomutase (PGM) phenotyping by PAGIEF. A total of 598 water extracts from casework bloodstains have been tested. Positive results were obtained in 84% and 75% of samples for PGM and A2HS respectively. The A2HS gene frequencies A2HS*1 = 0.6420, A2HS*2 = 0.3530, and A2HS*3 = 0.0050 were determined from a survey of 1000 people in Brisbane. PMID- 2584949 TI - A surprising case of endrin poisoning in dogs. AB - A case of possible malicious poisoning of dogs by endrin was investigated. A variety of tissues were analysed. The stomach contents of one dog contained 5 g/kg endrin. The results are compared with recorded data from feeding studies pursued elsewhere to aid the diagnosis of dieldrin and endrin intoxication. A number of organochlorine compounds closely related chemically to endrin were tentatively identified. PMID- 2584950 TI - The complete nucleotide sequence of coxsackievirus A21. AB - We have determined the complete nucleotide sequence of coxsackievirus A21 (CAV 21), the first member of this enterovirus subgroup to be analysed in molecular detail. The sequence, which is 7401 nucleotides long, encodes an open reading frame of 2206 codons, preceded by a 5' non-coding region of 711 nucleotides and followed by a 3' non-coding region of 72 nucleotides plus a poly(A) tract. The most striking feature is the remarkable homology to the poliovirus (greater than 90% at the amino acid level) in the 3' part of the genome. The rest of the genome is much less homologous, suggesting that CAV-21 is a recombinant virus. Rhinovirus-like characteristics, including the length of the 5' non-coding region and a slight --U/--A imbalance in codon usage, may be related to the fact that CAV-21, like rhinoviruses, infects the upper respiratory tract. However, the sequence sheds little light on the molecular basis of the shared receptor specificity. PMID- 2584951 TI - Nucleotide sequence of the capsid protein gene of barley yellow mosaic virus. AB - The sequence of the 3'-terminal 1370 nucleotides of barley yellow mosaic virus (BaYMV) RNA 1 was determined. The sequence contains a long open reading frame (ORF) of 1137 nucleotides and a non-coding region of 231 nucleotides upstream of the poly(A) tail. Mapping of the partial amino acid sequences of the capsid protein onto the putative translational product of the ORF indicates that the 3' proximal region of RNA 1 encodes the capsid protein which consists of 297 amino acids with an Mr of 32334; the capsid protein is produced by proteolytic processing from a precursor polypeptide at a glutamine-alanine dipeptide. The removal of the N- and C-terminal regions of the capsid protein by mild proteolysis of intact virus particles indicates that both terminal regions are exposed on the external surfaces of virus particles. Alignment of the BaYMV capsid protein sequence with those of some potyviruses showed only small blocks of homology which contrast with the extensive matches among potyviruses. This fact together with the genome organization and the vector specificity clearly distinguishes BaYMV from potyviruses. PMID- 2584952 TI - Nucleotide sequences of 5' and 3' non-coding regions of pepper mild mottle virus strain S RNA. AB - The nucleotide sequences of the 5' and 3' non-coding regions of pepper mild mottle virus strain S (PMMV-S) RNA were determined; they are more like corresponding sequences of tomato mosaic virus (ToMV) RNA than those of any other tobamovirus reported so far. The 5' leader contains a 68 nucleotide guanosine free sequence which differs in several nucleotides from the corresponding sequences in genomic RNA of tobacco mosaic virus (TMV) and ToMV. The messenger activity of PMMV-S RNA in vitro and the polypeptide translation products made were similar to those of TMV RNA. It therefore seems unlikely that qualitative or quantitative differences in translation in vivo account for the milder symptoms induced by PMMV-S, and its lesser replication, than TMV. The 3' non-coding region of PMMV-S RNA is 199 nucleotides long and can be folded into the same secondary structure as the RNA of other tobamoviruses. PMID- 2584953 TI - Coat protein of melon necrotic spot carmovirus is more similar to those of tombusviruses than those of carmoviruses. AB - Complementary DNA copies of the genomic RNA of melon necrotic spot virus (MNSV) have been cloned and the region deduced to encode the coat protein has been sequenced. The putative coat protein coding region, located near the 3' end of the genome, consists of 1170 nucleotides and has the potential to encode a 390 amino acid protein of Mr 41,840. Our data show that although MNSV is a carmovirus, its coat protein more closely resembles those of the tombusviruses than those of the carmoviruses sequenced to date, in both the extent of sequence similarity and in the length of the random/arm and protruding domains of the coat protein. Furthermore, dot matrix comparisons revealed sequence similarity between the coat protein protruding domains of MNSV and the cucumber necrosis tombusvirus. This similarity may be involved in one or more of the biological properties these two viruses share, such as the ability to infect cucumbers naturally and to be transmitted by the soil-inhabiting fungus Olpidium radicale. PMID- 2584954 TI - Expression of the human parvovirus B19 protein fused to protein A in Escherichia coli: recognition by IgM and IgG antibodies in human sera. AB - A 1.4 kb fragment (nucleotides 2430 to 3901) encoding portions of the human parvovirus B19 structural proteins was inserted into the pRIT2 plasmid expression vector containing the gene encoding staphylococcal Protein A under the control of the phage lambda promoter PR. The fusion protein was used to raise antibodies in rabbits. The sera were shown by immune electron microscopy to agglutinate B19 particles and were also shown to recognize the VP2 B19 capsid protein, by Western blot analysis. The B19 antigenicity of the fusion protein was confirmed by immunoblot and enzyme immunoassay with IgG and IgM anti-B19-positive reference human sera. PMID- 2584955 TI - Postpartum subsidence of hepatitis B viral replication in HBeAg-positive carrier mothers. AB - To elucidate the effects of pregnancy and delivery on hepatitis B e antigen (HBeAg)-positive carrier mothers, 31 HBeAg-positive carrier mothers were followed up postpartum 1 year, with 30 HBeAg-positive nonpregnant female carriers as controls. Serum hepatitis B surface antigen (HBsAg), HBeAg titer, and hepatitis B virus (HBV)-DNA concentration were studied at defined intervals. The results revealed that in the control group HBeAg titers and HBV-DNA concentrations fluctuated, whereas the HBsAg titers showed little change, but HBeAg clearance or seroconversion to anti-HBe were not noted on follow-up. In contrast, one carrier mother seroconverted to anti-HBe during pregnancy and the antibody persisted thereafter. Five of the remaining 30 carrier mothers cleared HBeAg postpartum, and among these five cases, one also seroconverted to anti-HBe. In addition, in another five of the 30 cases, the HBV-DNA fell to undetectable level (less than 0.04 ng/ml). All these ten cases had a common tendency of showing a decrease in HBeAg titers and/or HBV-DNA concentrations 1-2 months after delivery. The HBeAg titers and HBV-DNA concentrations in the other 11 cases remained unchanged, whereas the remaining nine cases had increased levels. It is concluded that subsidence of HBV replication is precipitated by delivery in one-third of HBeAg positive carrier mothers in Taiwan, and this occurs most frequently 1-2 months postpartum. PMID- 2584956 TI - Control of HBV and HDV infection in an isolated Pacific Island: 1. Pattern of infection. AB - Hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections are known to be hyperendemic in Nauru. Because of the consequences of chronic HBV infection, the Nauruan Government has commenced a program that aims to reduce and eventually eliminate hepatitis B infection by immunizing susceptible adults and children on the island and every newborn baby. At the outset of this program, a national seroepidemiological survey was undertaken. Eighty-eight percent of the population were tested, of whom 69.1% had markers of HBV infection. Evidence of superinfection with HDV was found in 22.7% of HBV carriers, with the highest prevalence in adolescents and young adults. All seronegative individuals were offered three doses of plasma derived hepatitis B vaccine. A post-vaccination survey of 64% of those vaccinated showed that 98% had developed circulating antibodies. PMID- 2584957 TI - Elimination of circulatory IgM anti-HSA precedes anti-HBe seroconversion in patients with CAH type B. AB - The presence of IgM and IgA antibodies with specificity for human serum albumin (HSA) were consecutively analyzed in serum samples from four patients with biopsy verified CAH type B during seroconversion in the HBe/anti-HBe antigen system. Circulatory IgM anti-HSA antibodies were present during HBe antigenemia. The antibody titers fluctuated, decreased, and were finally lost from the circulation. After the disappearance of IgM anti-HSA antibodies, seroconversion to anti-HBe reactivity occurred and a quiescent phase of the disease was established, as judged by normalization of transaminases and absence of circulatory HBV-DNA. IgA anti-HSA antibodies persisted in the circulation after the elimination of IgM anti-HSA and seroconversion to anti-HBe reactivity. For one of the patients, a dramatic increase in titers was followed by elimination of IgA anti-HSA and seroconversion to anti-HBs. The data indicate that the host "self"-component HSA, when associated with "foreign" HBe or HBs antigenic structures, elicit immune responses to HSA, preventing the adequate development of anti-HBe and anti-HBs. The cessation of anti-HSA reactivity, however, seemed to permit subsequent sensitization to HBe and HBs antigenic determinants, as detected by the presence of circulatory antibodies. PMID- 2584958 TI - Hepatitis delta virus infections in intravenous drug abusers with hepatitis B in the west of Scotland. AB - The prevalence of delta virus infection was studied in 264 intravenous drug abusers (IVDAs) whose sera were found to be HBsAg positive between 1985 and 1987 and in 15 IVDAs from the period 1971-75, seven from 1976, 15 from 1979, and 37 from 1982. Delta markers were present in 41% of IVDAs with acute hepatitis B and in 65% of those who were chronic HBsAg carriers between 1985-87. The first evidence of delta virus infection was found in 1975. In 1976, 1979, and 1982, respectively, 42, 63, and 5% of IVDAs with acute hepatitis B had delta coinfection. In the West of Scotland, delta infection has been established in the IVDA population since 1975. The very high percentage of IVDA carriers superinfected with the delta virus implies that there will be an excess of patients presenting with severe liver disease in the future. PMID- 2584959 TI - Detection of human coronavirus 229E in nasal washings using RNA:RNA hybridisation. AB - A method is described for the detection of human coronavirus 229E (HCV 229E) in nasal washings using RNA:RNA filter hybridisation. Volunteers were inoculated with HCV 229E, and daily nasal washings were collected. These washings were then examined for the presence of viral RNA using a single-stranded RNA probe. Nucleic acid hybridisation is shown to be a sensitive technique for the diagnosis of HCV 229E infections. PMID- 2584960 TI - Autoradiographic identification of ecdysteroid-binding cells in the nervous system of the moth Manduca sexta. AB - The steroid hormone 20-hydroxyecdysone regulates many aspects of nervous system development in the moth Manduca sexta, including stage-specific neuronal morphology and stage-specific neuronal death. We have used steroid hormone autoradiography to study the distribution of cells that concentrate ecdysteroids in the ventral nervous system of this insect. The ligand was [3H]-ponasterone A, a bioactive phytoecdysone. Tissue was examined from three stages of development: the end of larval life (first day of wandering), the end of metamorphosis (pharate adult), and 4-day-old adults. In the abdominal ganglia of wandering larvae and pharate adults, a subset of neurons including both motoneurons and interneurons exhibited a nuclear concentration of radiolabeled hormone. The pattern of binding was reproducible but stage-specific, with a greater proportion of neurons showing binding in the larvae than in pharate adults. No labeled neurons were found in abdominal ganglia from mature (4-day-old) adults. In the case of the pharate adult ganglia, the ecdysteroid receptor content of specific, identified motoneurons was determined. These results are discussed in light of the responses of these neurons to physiological changes in levels of circulating ecdysteroids. PMID- 2584961 TI - Regeneration of an identifiable motoneuron in the crayfish. I. Patterns of reconnection and synaptic strength established in normal and altered target areas. AB - The superficial flexor muscles of the crayfish are innervated in a position dependent connectivity pattern, which can be reestablished when the nerve to the muscle is cut. This article deals with the regeneration of the largest excitor motoneuron under three different target scenarios: (1) a normal target with all the muscle fibers present, (2) a reduced target lacking the medial or the lateral muscle fiber population, and (3) when the nerve enters the target in the middle of the muscle field. In scenario 1 the neuron is able to regenerate the normal connectivity pattern within 10 weeks after surgery: all the lateral fibers become innervated, with a linear decline in the probability of connections over the medial fibers. The medial fibers become transiently hyperinnervated before the normal pattern of connections is established. In scenario 2 the normal pattern of connections is established only when the lateral fibers were present; with only medial cells as a target, the transient hyperinnervation stage is stable and no decline in connections was observed. Analysis of regenerated junction potential sizes during the stable hyperinnervation stage show abnormal patterns, suggesting that some aspects of the regeneration program of this neuron can be affected when signals from its prime target cells are missing. In scenario 3 growth begins in both directions until the entire muscle becomes innervated. The normal pattern of connectivity finally emerges after continued lateral growth and diminished medial growth, suggesting that the position of the muscle fibers influences connectivity patterns during the final stages of regeneration. PMID- 2584962 TI - Regeneration of an identifiable motoneuron in the crayfish. II. Patterns of reconnection and synaptic strength established in the presence of an extra nerve. AB - The regeneration of neuromuscular connections to the superficial flexor muscle system in the crayfish has been studied under a variety of experimental manipulations. These have provided insight into the factors that can influence the regeneration program of neurons. In this work the regeneration of the largest excitor motoneuron was studied under two different conditions: (1) when the original neuron and a transplanted neuron were growing simultaneously into a denervated target, and (2) when a transplanted neuron was growing into a target that had its original nerve supply intact. In condition 1 both the transplanted and the original neuron formed normal patterns of connectivity and synaptic strength in comparable periods of time. In condition 2 the rate of growth of the transplanted neuron is significantly reduced and does not extend into the lateral fibers of the muscle. It is concluded that the regeneration program of this neuron is not affected by the presence of other neurons growing at the same time into a denervated muscle. Since regeneration is seriously affected if growth occurs into a fully innervated target area, it is suggested that lack of growth stimuli from the target or competitive interactions between established and growing synaptic terminals could influence the regeneration program of this neuron. PMID- 2584963 TI - Aminergic cellular organization in the gills of Aplysia species. AB - The constituent elements of the gills of Aplysia kurodai and A. juliana were examined for the presence of biogenic amines using histochemical, immunocytochemical, and HPLC techniques. Aminergic elements were revealed by glyoxylic acid-induced fluorescence in the branchial nerve, branchial ganglion, branchial vessels, and pinnules in both species. Three types of fluorescent cells were found in the neural plexus of the gill in each species. Two of them might be sensory neurons. Although HPLC analysis showed the presence of serotonin and dopamine in all gill structures including fluorescent neural elements, there were regional differences in concentrations of the monoamines. It was noted in the pinnules that there was a much higher concentration of dopamine than serotonin. Serotonin immunocytochemistry revealed neural processes which were immunoreactive to antiserotonin antibody, but serotonin immunoreactivity could not be found in a population of branchioganglionic neuron (BGN) somata. Serotonergic elements in the ganglion may be processes of the central ganglion, while dopaminergic elements may be processes of neurons in the neural plexus, located beyond the branchial ganglion. BGNs were activated by bath-applied dopamine and serotonin. These results suggest that dopaminergic sensory inputs from the neural plexus and serotonergic descending inputs from the abdominal ganglion may be among the inputs received by BGNs. It was found that serotonin depressed excitatory junctional potentials in muscle cells of the efferent branchial vessel, which were induced by an identified neuron of the abdominal ganglion. The aminergic cellular organization of the gill may involve serotonergic presynaptic-inhibitory fibers arising from the abdominal ganglion. PMID- 2584964 TI - Multiple cAMP-binding proteins in Aplysia tissues. AB - While it is recognized that cAMP is able to regulate distinct cellular processes differentially, the molecular basis for the diversity of its effects remains unclear. Using photoaffinity labeling with 32P-8 azido-cAMP and two-dimensional gel analysis, we have identified 26 electrophoretic variants of cAMP-binding proteins in the six different tissues of the marine mollusc Aplysia californica sampled. Some of these proteins are found in most tissues, others only in a few; still others appear to be restricted to a single tissue. All of these proteins bind cAMP specifically. The two-dimensional polyacrylamide gel electrophoretic patterns of binding proteins seen in the different tissues fall into three classes. One pattern is shared by the nervous system and embryos. The second is found in muscular tissues (heart, buccal muscle, siphon, and gill). The third pattern is specific to sperm. The presence of distinct subsets of cAMP-binding proteins in different tissues suggests that at least some of the diversity in cAMP's regulatory function may result from diversity in the proteins that bind it. PMID- 2584965 TI - Localization of the enhanced input to cockroach giant interneurons after partial deafferentation. AB - The ventral giant interneurons (GIs) in the cockroach have two distinct dendritic fields: a small one ipsilateral to the soma, and a larger, contralateral field from which the axon arises. The major input to these GIs is from the cercus on the axon side; when this cercus is ablated in the last instar before the adult stage, input from the other cercus becomes more effective within 30 days (Vardi and Camhi, 1982b). I wished to determine if the input from the intact, soma ipsilateral cercus contacted the GIs purely ipsilaterally and if EPSPs at this site were larger in deafferented animals. Consistent with earlier anatomical findings, intracellular recordings from the GI somata showed that the majority of cercal inputs synapse on their own side of the ganglion in normal animals. This was evidenced by differences in the size and shape of the synaptic potentials evoked from the two cerci and by the presence of large EPSPs after a ganglion had been split along the midline. Unitary EPSPs produced by stimulation of single, identified cercal afferents, ipsilateral to the soma, were compared between normal and deafferented animals. Column "h" afferents were chosen because they make a large contribution to the receptive fields of GIs 1 and 2 after ablation of the contralateral cercus. In addition, the arbors of these afferents, when stained with cobalt, did not cross the ganglionic midline in normal animals. Unitary EPSPs recorded in GI 2 were significantly larger in the deafferented animals. There was, however, no significant change in the size of EPSPs in GI 1. Nevertheless, the results from GI 2 suggest that partial deafferentation in the central nervous system can increase the efficacy of synapses distant from the locus of denervation. PMID- 2584966 TI - Identification of species D, a new member of the Anopheles quadrimaculatus species complex: a biochemical key. AB - Sibling species D, a new member of the Anopheles quadrimaculatus species complex was identified in collections from Pickwick Lake, Tishomingo County, Mississippi and Choctawhatchee, Bay County, in West Florida. This species occurred sympatrically with the previously described species, A, B and C. Evidence for identification of species D includes diagnostic allozymes, a lack of polytene chromosomes in the ovarian nurse cells, and inviability of F1 progeny and lack of sperm transfer in hybridization crosses. An electrophoretic taxonomic key for distinguishing species D from A, B and C is presented. PMID- 2584968 TI - Biting and resting behavior of Anopheles darlingi in the Suriname rainforest. AB - An experimental hut study was conducted on the biting and house resting behavior of Anopheles darlingi in the rainforest of Suriname. Of all anophelines collected on human bait at indoor and peridomestic sites, An. darlingi comprised 100% and 98%, respectively. A single peak in biting activity occurred around 2300 h. With hourly exit trap collections, a peak of exit from the hut was observed at sunrise. Of these mosquitoes, 91% were freshly fed. The indoor resting period was calculated to be about 4 h. When the human bait in the hut was protected by a mosquito net, only 18% of the exiting mosquitoes were fed and the resting period was about 3 h. PMID- 2584967 TI - Behavioral responses of Anopheles darlingi in Suriname to DDT residues on house walls. AB - A study was conducted in Suriname on the effects of DDT residual house spray on the main vector of malaria, Anopheles darlingi. Results obtained with an experimental hut sprayed with DDT wettable powder (2 g/m2 AI) were compared with results obtained with an unsprayed control hut. In the sprayed hut, entry rates were reduced by 32% and feeding success by 43.6%. The 24-h mortality of mosquitoes which entered the sprayed hut was 95% (range 85-100%) over the 10 month study period. After furnishing the sprayed hut according to local custom, no reduction in mortality was observed despite an abundance of unsprayed resting surfaces. Bioassays showed that the DDT deposits remained effective for at least 14 months. With excito-repellency test boxes an irritant effect caused by DDT on recently fed An. darlingi females was shown. With a choice-box experiment no preference for unsprayed over sprayed resting places could be demonstrated. PMID- 2584969 TI - Efficacy of diethyl methylbenzamide (deet) against Aedes dorsalis and a comparison of two end points for protection time. AB - The repellent deet (N,N-diethyl-3-methylbenzamide) was tested against the mosquito Aedes dorsalis in a coastal salt marsh in California. The experimental design incorporated a multiple regression model, sequential treatments and a proportional end point (95%) for protection time. The ED95 (95% effective dose) and 4-h ED95 were estimated at 0.05 mg/cm2 and 0.09 mg/cm2, respectively. The 0.05 mg/cm2 protection time and 0.10 mg/cm2 protection time were estimated at 0.2 h and 4.4 h. The decay constant and half-life were estimated at 0.17 h-1 and 4.1 h. The design and analysis of repellent field trials are discussed. PMID- 2584970 TI - A field trial of ethyl hexanediol against Aedes dorsalis in Sonoma County, California. AB - The repellent ethyl hexanediol (2-ethyl-1,3-hexanediol) was tested against the mosquito Aedes dorsalis in a coastal salt marsh in California. The experimental design incorporated a linear regression model, sequential treatments and a proportional end point (95%) for protection time. The protection time of 0.10 mg/cm2 ethyl hexanediol was estimated at 0.8 h. This time is shorter than that obtained previously for deet (N,N-diethyl-3-methylbenzamide) against Ae. dorsalis (4.4 h). PMID- 2584971 TI - Relative suitability of Aedes albopictus and Aedes aegypti in North Carolina to support development of Dirofilaria immitis. AB - The relative suitability of two colonies established from local strains of Aedes albopictus (Wilmington and Rockingham) and a local (Raleigh) and laboratory (Liverpool) strain of Ae. aegypti to support development of Dirofilaria immitis was investigated. High levels of mortality occurred 1-2 days after mosquitoes fed on a heavily microfilaremic (28,617 microfilariae/ml) dog but not when mosquitoes were fed on a dog exhibiting a moderate microfilaremia (3,300 microfilariae/ml). At 15-16 days postfeeding, development of D. immitis to the third larval stage occurred to some extent in mosquitoes of all four strains. Microfilariae were only found in the Raleigh strain of Ae. aegypti. Aedes albopictus most frequently contained first and second stage larvae that were deteriorated which suggested that their development had been arrested. Third stage larvae were found most often in the Liverpool strain of Ae. aegypti. Colonies established from local strains of Ae. albopictus and Ae. aegypti do not appear to be suitable hosts of D. immitis. PMID- 2584972 TI - Environmental factors affecting mortality of adult Culicoides variipennis (Diptera: Ceratopogonidae) in the laboratory. AB - The effects of several environmental factors on mortality of adult Culicoides variipennis in the laboratory were evaluated. Daily mortality rates significantly increased when adult midges were maintained at an elevated constant temperature (26 degrees C). Adult C. variipennis handled the least during routine maintenance procedures had the lowest daily mortality rate. Survival was not significantly affected by varying density levels of adult midges in the size of container routinely used in our laboratory. Implications of these observations using adult C. variipennis for future studies are discussed. PMID- 2584973 TI - Prey-size selection by Triops longicaudatus (Notostraca: Triopsidae) feeding on immature stages of Culex quinquefasciatus. AB - The tadpole shrimp, Triops longicaudatus, was found to be a size-dependent predator of Culex quinquefasciatus larvae in the laboratory. However, changes in tadpole shrimp size were accompanied by changes in prey-size preference: larger sized predators consumed an increasing proportion of larger prey items. Very large tadpole shrimp may be nonselective predators of this mosquito species. Quantified behavioral observations indicated that while second instar mosquito larvae were encountered significantly less frequently than were fourth instar larvae or pupae, they were captured at significantly greater rates and with shorter handling times. It is hypothesized that prey vulnerability has an important influence on tadpole shrimp prey size "preferences." PMID- 2584974 TI - A broad evaluation of B.t.i. for black fly (Diptera: Simuliidae) control in a Michigan river: efficacy, carry and nontarget effects on invertebrates and fish. AB - Efficacy for black fly control, carry and nontarget effects of B.t.i. (Teknar HP D), applied in the Betsie River, Michigan, were studied in June 1988. Black fly mortality was high (approximately 100%) for a 2,200 m stretch downstream from the application site, declined to 30% at 3,200 m, and was nil at 4,500 m. Drift of black flies greatly increased after application at a downstream site, but did not change at an upstream site. There were no detectable nontarget effects of B.t.i. application on: 1) invertebrate macro- or micro-drift; 2) numbers of invertebrates in benthic Surber samples; 3) mortality or feeding of drifting and nondrifting insects; 4) growth or mortality of caged Stenomena sp. larvae; 5) invertebrate functional group composition; 6) mortality or weight change of caged rock bass; or 7) fish numbers, species composition, length-weight (rock bass only) relationships or rock bass diet. Sampling of Rheotanytarsus sp. midges on natural substrates indicated low (27%) mortality owing to B.t.i. at only 100 m downstream from the application site, with negligible mortality at all other downstream and upstream sites. This information, combined with no pronounced changes in numbers of midges in macro-drift after application, indicated that midge populations were not adversely affected by B.t.i. in the study. PMID- 2584975 TI - Interspecific mating between Louisiana strains of Aedes albopictus and Aedes aegypti in the field and laboratory. AB - Interspecific mating between Aedes albopictus males and Ae. aegypti females was detected in the field using mark-release-recapture techniques. By 3 days after the release of virgin Ae. aegypti females into a field site containing only Ae. albopictus, 100% of the captured females were inseminated. Laboratory investigations indicated that male Ae. albopictus were very proficient at inseminating Ae. aegypti females and that Ae. aegypti males rarely inseminated Ae. albopictus females, especially if Ae. aegypti females were available. Most of the Ae. aegypti females inseminated by Ae. albopictus males contained only small amounts of dead sperm in their spermathecae, while inseminated females from the converse interspecific mating and from intraspecific matings contained only large amounts of live sperm. The results are discussed in relation to the decline in Ae. aegypti densities observed since the introduction of Ae. albopictus into the southern USA. PMID- 2584976 TI - Recently introduced Aedes albopictus in the United States: potential vector of La Crosse virus (Bunyaviridae: California serogroup). AB - A population of Aedes albopictus collected in 1986 in Harris County, Texas, was evaluated for its vector competence with 4 California serogroup viruses (Jamestown Canyon, Keystone, La Crosse and trivittatus). Rates of midgut infection, dissemination of virus beyond the midgut and oral transmission to suckling mice were markedly different for the 4 viruses in a pattern representative of the antigenic relationships known for the California serogroup. Only La Crosse virus was shown to be efficiently transmitted by this recently introduced mosquito population. The results suggest that populations of Ae. albopictus originating from the Harris County population might well be as efficient in transmitting La Crosse virus as are populations of the natural mosquito vector. Aedes triseriatus, from the midwestern La Crosse virus enzootic region. The public health implications of these results are discussed in relation to the rapid spread of Ae. albopictus throughout the eastern half of the United States and into regions where La Crosse virus is known to be enzootic. PMID- 2584978 TI - An improved laboratory test cage for testing repellents on human volunteers. PMID- 2584977 TI - An electrically controlled pesticide agitation system for rotary-winged aircraft mounted sprayers. PMID- 2584979 TI - Records of Aedes albopictus, Ae. aegypti and Ae. triseriatus from the U.S. Air Force ovitrapping program--1988. PMID- 2584980 TI - Parasitism of adult Aedes vexans by a mermithid (Nematoda: Mermithidae) in Iowa. PMID- 2584981 TI - Unicompartmental knee arthroplasty. A 4.5-6-year follow-up study with a metal backed tibial component. AB - The results in the first 50 patients to receive an improved-design unicompartmental knee prosthesis were reviewed after an average follow-up period of 5.5 years. The prosthesis is composed of a metal-backed polyethylene tibial component and a wide femoral surface replacement that are fixed to bone with acrylic cement. Forty-five patients with 55 unicompartmental knee arthroplasties were available for clinical study. Ninety-two percent of the knees were rated as having a good or excellent result, and 94% had lasting relief of pain. There have been no failures requiring revision. A radiographic review demonstrated that no tibial component was bordered by a complete radiolucent line. There was no subsidence or loosening of either the tibial or femoral components, and there was no instance of local osteolysis. These results, coupled with a 14-year follow-up experience with the original-design unicondylar prosthesis, encourages the authors to remain advocates of this procedure in selected patients with unicompartmental osteoarthritis. PMID- 2584982 TI - Total knee arthroplasty following high tibial osteotomy for osteoarthritis. AB - The authors assessed the effect of proximal tibial osteotomy on the results of a subsequent total knee arthroplasty. A retrospective, clinical and radiographic analysis was carried out between a study group of 39 patients with 42 total knee arthroplasties following osteotomy and a control group of 39 patients with 41 primary arthroplasties. Outcome was assessed using the Hospital for Special Surgery (HSS) knee score, pain, function, range of motion, and radiographic evaluation. The follow-up period averaged 37 months (range, 24-50 months). The study group had 88% good or excellent results using the HSS score, compared to 90% in the control group. Function and pain improved equally in both groups. The control group had, on average, 14 degrees greater range of motion (115 degrees v. 101 degrees) after arthroplasty. The control group had, on average, posterior inclination of the tibial plateau of 7 degrees before operation and 3 degrees after operation; the corresponding values in the study group were 2 degrees and 1 degree. Using the HSS score and pain and function as parameters, previous osteotomy does not seem to affect the outcome of total knee arthroplasty. Conversely, range of motion following arthroplasty appears to be less in those with prior osteotomy. In addition, a high tibial osteotomy may alter the inclination of the tibial plateau. PMID- 2584983 TI - Fracture of polyethylene of patellar component in total knee arthroplasty, diagnosed by arthroscopy. AB - Three reports of fracture of the polyethylene of the patellar component in total knee arthroplasty are presented. The value of arthroscopy in providing the correct diagnosis of this unusual complication of total knee arthroplasty is emphasized. PMID- 2584984 TI - Treatment of major wound necrosis following total knee arthroplasty. AB - Following total knee arthoplasty, seven patients developed significant wound necrosis and dehiscence, requiring wound coverage with soft tissue flaps. Three patients had rheumatoid arthritis, three had degenerative arthritis, and one had osteosarcoma of the distal femur. Five different prostheses were used and the wound problems were discovered on average 21 days after arthroplasty. The average wound size was 6.0 cm2. Five were infected, four with Staphylococcus epidermidis and one with Staphylococcus aureus. All patients were treated with antibiotics and local debridement for an average of 10 days prior to the flap procedure. Medical gastrocnemius muscle flaps were used in two patients, unipedicle flaps transposed from the lateral thigh in three, and bipedicle flaps shifted from the medial thigh in two. Flaps were done an average of 56 days after arthroplasty, and knee rehabilitation was delayed an average of 76 days after arthroplasty. Patients were followed an average of 48 months after the flap procedure. Six patients had mild or no knee pain and one who remained infected had moderate constant pain. Three of the patients had greater than 90 degrees of knee motion and one had 75 degrees of motion. The remaining three had only 35 degrees of motion, due in part to significant preoperative contractures, infection, local radiation, and chemotherapy. Late infection developed in two patients at 20 and 45 months following the flap procedure. There was one excellent, three good, two fair, and one poor result using the Hospital for Special Surgery knee rating system at final follow-up examination. PMID- 2584986 TI - Abrasion arthroplasty as a salvage for failed upper tibial osteotomy. AB - Eight patients with persistent pain after upper tibial osteotomy and correction of malalignment were treated with abrasion arthroplasty of the affected compartment. At 34-month follow-up examination, only one patient had significant lasting benefit. Five of the patients required subsequent total knee arthroplasty for relief of their pain. One patient was symptomatically unchanged, and one was awaiting total knee arthroplasty. The authors conclude that abrasion arthroplasty is not a satisfactory salvage for a failed upper tibial osteotomy. PMID- 2584985 TI - Quantitative histologic analysis of tissue growth into porous total knee components. AB - Histologic and radiographic analysis was performed on 85 porous-coated, uncemented knee components (26 femoral, 34 tibial, and 25 patellar) retrieved from 45 patients for malposition or instability, unexplained pain, late infection, postmortem or postamputation, and posttrauma. No component was clinically or radiographically loose at the time of removal. The average patient age at removal was 62.1 years (range, 39-85 years), and the average time in situ was 12.4 months (range, 2 weeks to 53 months). Radiographs from 31 of the 45 patients (69%) were examined for implant alignment, fit, subsidence, loose beads, and the presence of sclerotic and lucent lines. Histologic and microradiographic sections of the implant and adherent tissue were examined for type, amount, and anatomic location of tissue ingrowth. Overall, 52% of the components showed no evidence of bone ingrowth, 29% showed minimal (less than 2%), 12% showed moderate (2-5%), and 7% showed extensive (5-10%) bone ingrowth. In no case was bone present in more than 10% of the available pore volume of any component. There were no significant differences in the incidence or extent of bone ingrowth among femoral, tibial, and patellar components, nor in the extent of bone ingrowth observed in comparing different implant designs, materials, or porous coating types. When bone ingrowth was observed, the anatomic location was consistent in each type of component. The presence of a lucent line radiographically was indicative of fibrous encapsulation, while a sclerotic line or absence of any radiographic abnormality was seen with both fibrous tissue and bone ingrowth. PMID- 2584987 TI - 10-year evaluation of compartmental knee arthroplasty. AB - The author describes the clinical outcome 10 years after unicompartmental knee arthroplasty according to a knee assessment system, developed by Tew and Waugh, that includes a detailed operational identification of the clinical examination. Sixty percent had a good or excellent results using this method, versus 75% using the Hospital for Special Surgery knee assessment system. Seventy percent of the patients were still satisfied with their knee at follow-up evaluation, 59% could step up and 48% down from a 30-cm platform in a normal way. About 35% of the patients who could not step up and down from a 30-cm platform were handicapped by factors other than their knee. There was no extensor lag. The median for coronal tibiofemoral angle was 176 degrees, for coronal bidirectional instability was 1 degree, for active flexion was 109 degrees, for active extension was 5 degrees, for range of motion was 107 degrees, and for change of flexion from before arthroplasty was 0 degrees. In 56% of the knees the patellofemoral joint alone or in combination with the tibiofemoral joint had abnormal symptoms or signs. PMID- 2584988 TI - Alignment of total knee arthroplasty. AB - A series of 65 total knee arthroplasties performed by the senior author was evaluated to determine the effect of alignment on outcome. Radiographs and results of clinical examination were reviewed. Sixty-one of the 65 knees were in varus on the mechanical axis (ie, the weight-bearing line passed through the medial compartment). At an average follow-up period of 48 months, alignment was not found to affect incidence or progression of radiolucent lines, changes in tibial metaphyseal density, or clinical outcome (pain or range of motion). The authors were unable to confirm the historical belief that alignment is critical to the durability of cemented total knee arthroplasty, nor that the mechanical axis must pass through the center of the knee joint. PMID- 2584989 TI - Patellar fractures in total knee arthroplasty. AB - The incidence of patellar fractures following total knee arthroplasty varies from 3% to 21%. This problem has been attributed to avascular necrosis of the patella secondary to the surgical approach, including medial arthrotomy and lateral release, patellar bone resection, thermal necrosis, and anatomic variation. Management of these patellar fractures may be conservative or surgical. PMID- 2584990 TI - The patellofemoral joint in total knee prostheses. Design considerations. AB - Some desirable design features of the patellofemoral joint in a total knee arthroplasty condylar prosthesis are proposed. These are that the femoral element should be grooved, have a high anterior flange, and be circular as viewed from the side. The groove should be about 5 mm deep and have relatively vertical walls. The patellar component should have a saddle-shaped articular surface matching the femur and should be countersunk into the patella. The components should be placed so as to position the joint automatically. Results with such a design are reported; loosening, wear, dislocation, and fracture have been rare. Osteolysis of the patella has not been seen after 9 years, so that the cementless press-fit fixation of an H.D.P. patellar prosthesis to date seems safe and efficacious. PMID- 2584991 TI - Blood supply to the patella. Significance in total knee arthroplasty. AB - Patellofemoral problems occur in approximately 5% of total knee arthroplasties and account for 50% of complications of total knee arthroplasty. Surgical disruption of the blood supply to the patella may cause an increase in the incidence of osteonecrosis, stress fracture, and loosening. The authors discuss patellar blood supply and surgical considerations in total knee arthroplasty and review the clinical experience with avascular patellae. PMID- 2584992 TI - Nonresurfaced patella in total knee arthroplasty. AB - Problems attributable to the patellofemoral joint are still the major cause of disability in contemporary knee arthroplasty. Patellar resurfacing does lead to further complications, such as loosening, wear, and malalignment. Two studies have been performed specifically to review experience with the nonresurfaced patella in total knee arthroplasty. The first study determined that patellofemoral symptoms occurred in 8% of the total group and the majority of these were due to patellar malalignment. The postoperative skyline views at 60 degrees and 90 degrees of flexion obtained routinely identified dynamic patellar maltracking responsible for anterior knee pain. The second study addressed long term durability of the nonresurfaced patella. The tracking of the patella was maintained with only small shifts of patella position and the tendency to stabilize with time. Stress-induced bone remodelling, particularly of the lateral facet, occurred in 85% of patellae. No preoperative or postoperative radiologic variable was associated with anterior knee pain. The authors strongly recommend that accurate patellofemoral tracking be obtained at the time of knee arthroplasty by staged procedures, with removal of peripheral osteophytes, then proximal iliotibial tract release followed by lateral debulking to a marked degree to obtain neutral tracking. Only then will intracapsular lateral release be performed. The results presented support the use of the nonresurfaced patella, and patellar malalignment remains a major source of disability attributable to the patellofemoral joint following total knee arthroplasty. PMID- 2584993 TI - Patellofemoral instability in total knee arthroplasty. AB - Patellofemoral instability following total knee arthroplasty remains one of the major complications requiring operative intervention. In spite of recent advances in technique and instrumentation, the rate of this complication remains disturbingly high. A comprehensive analysis of cause reveals malalignment of any of the components to be potentially responsible, particularly valgus or internal rotation malalignment of either femoral or tibial component, as well as lateral displacement of the patellar component. Underresection of the patella or oversizing the femoral component may also contribute to excessive lateral retinacular tightness. When confronted with patellofemoral instability, the surgeon must first look for and correct the cause. Component malalignment requires component revision. Extensor mechanism imbalance requires either proximal or distal realignment. Lateral release alone invites recurrence of the problem. PMID- 2584994 TI - Predicting respiratory morbidity from pulmonary function tests: a reanalysis of ozone chamber studies. AB - Some consequences of acute exposure to ozone are best measured in studies of human respiratory responses in controlled exposure chambers. These studies typically examine relationships between exposures to alternative pollutant concentrations and indicators of lung function as measured by spirometry, such as forced expiratory volume in one second, FEV1. However, the association of respiratory morbidity with these changes in lung function is not well established. To gain a better understanding of the relationship between ozone related changes in pulmonary function and respiratory symptoms, data from several clinical studies have been reanalyzed. Logistic regression models were used to determine the quantitative relationship between changes in FEV1 and the probability of a mild or moderate lower respiratory symptom. Models were developed that corrected for repeated sampling of individuals and both population averaged and subject-specific effects were determined. The results indicate the existence of a strong and consistent quantitative relationship between changes in lung function and the probability of a respiratory symptom. Specifically, a 10 percent reduction in FEV1 is associated with a 15 percentage point increase in the probability of a mild, moderate or severe lower respiratory symptom and a 6 percentage point increase in the probability of a moderate or severe lower respiratory symptom. PMID- 2584996 TI - Indoor exposure to airborne particles and nitrogen dioxide during an air pollution episode. PMID- 2584997 TI - Health effects of ozone. Critical review discussion papers. PMID- 2584995 TI - Alteration in carboxyhemoglobin concentrations during exposure to 9 ppm carbon monoxide for 8 hours at sea level and 2134 m altitude in a hypobaric chamber. AB - Seventeen non-smoking young men served as subjects to determine the alteration in carboxyhemoglobin (COHb) concentrations during exposure to 0 or 9 ppm carbon monoxide for 8 hours (CO) at sea level or an altitude of 2134 meters (7000 feet) in a hypobaric chamber. Nine subjects rested during the exposure and 8 exercised for 10 minutes of each exposure hour at a mean ventilation of 25 L (BTPS). All subjects performed a maximal aerobic capacity test at the completion of their respective exposures. Carboxyhemoglobin concentrations fell in all subjects during their exposures to 0 ppm CO at sea level or 2134 m. During the 8-h exposures to 9 ppm CO, COHb rose linearly from approximately 0.2 percent to 0.7 percent. No significant differences in uptake were found whether the subjects were resting or intermittently exercising during their 8-h exposures. COHb levels attained were similar at both sea level and 2134 m. Maximal aerobic capacity was reduced approximately 7-10 percent consequent to altitude exposure during 0 ppm CO exposures. These values were not altered following exposure for 8 h to 9 ppm CO in either the resting or exercising subjects. PMID- 2584998 TI - Valveless sampling of ambient air for analysis by capillary gas chromatography. AB - A method for the high resolution, high sensitivity analysis of polluted air for individual organic compounds is described. Samples collected from 50 mL of ambient air at 87 K (liquid argon) are injected without use of a valve into a silica capillary column which is then temperature programmed from -30 degrees C to 180 degrees C. Hydrocarbons (4 to 10 carbons) as well as carbonyl compounds, chlorinated compounds and terpenes can be identified and quantified. The detection limit, not strongly dependent on carbon number, is estimated to be 0.3 ppbc in a 50 mL sample. Use of small samples eliminates the need to remove water vapor, a procedure which might jeopardize sample integrity. PMID- 2585000 TI - The impact of add-on catalytic devices on pollutant emissions from unvented kerosene heaters. PMID- 2584999 TI - Evaluation of canisters for measuring emissions of volatile organic air pollutants from hazardous waste incineration. AB - Regulation to control air emissions of toxic organic compounds require the collection and analysis of effluent gas from low level sources such as hazardous waste incinerators. The standard SW-846 Method specifies the use of Tenax and Tenax/charcoal adsorbent traps for collection of volatile organics from incinerators. This study evaluates passivated stainless steel canisters as an alternative to adsorbent traps to eliminate some of the problems associated with adsorbent sampling. Initially the stability of 18 nonpolar, volatile organic compounds was determined in Summa-treated stainless steel canisters with greater than 100 ppmv HCl and saturated with water vapor. All 18 components were stable for a two-week period; however, an interference caused a 10-fold increase in the FID response of trichloroethylene, toluene, and chlorobenzene. No interference of the ECD response was found for any of the 11 compounds detected with the ECD including trichloroethylene. A pilot scale incinerator was sampled using canisters, and the destruction efficiency of 1,1,1-trichloroethane was determined at a concentration of less than 0.5 ppbv while determining 1,1-dichloroethylene, the major product of incomplete combustion, at a concentration of 8000 ppbv from the same sample. PMID- 2585001 TI - GEOM: a new tool for molecular modelling based on distance geometry calculations with NMR data. AB - GEOM is a new graphics tool which allows the use of distance geometry to compute linear and cyclic structures typically arising in drug design situations. Modified amino acids or monomeric organic entities can be easily constructed in an interactive way and deposited in the library of the distance geometry program together with geometric information required for structure calculation in dihedral angle space. In addition, GEOM is able to produce all files needed to calculate a structure based on NMR data (NOE and J-coupling constraints) and it permits the graphic analysis and comparison of computed structures. The application of GEOM is demonstrated in three examples: modelling of cyclosporin A structures with and without a limited set of H-bond constraints and modelling of a cyclic hexapeptide with a full NMR data set. PMID- 2585002 TI - Theoretical studies of the mechanism of the action of the neurohypophyseal hormones. I. Molecular electrostatic potential (MEP) and molecular electrostatic field (MEF) maps of some vasopressin analogues. AB - Continuing our theoretical studies of the oxytocin and vasopressin analogues, we have analysed the molecular electrostatic potential (MEP) and the norm of the molecular electrostatic field (MEF) of [1-beta-mercaptopropionic acid]-arginine vasopressin ([ Mpa1]-AVP), [1-(beta-mercapto-beta,beta cyclopentamethylene)propionic acid]-arginine-vasopressin ([Cpp']-AVP), and [1 thiosalicylic acid]-arginine-vasopressin ([Ths']-AVP) whose low-energy conformations were calculated in our previous work. These compounds are known from experiment to exhibit different biological activity. The scalar fields mentioned determine the energy of interaction with either charged (MEP) or polar (MEF) species, the energy being in the second case either optimal or Boltzmann averaged over all the possible orientations of the dipole moment versus the electrostatic field. The electrostatic interactions slowly vanish with distance and can therefore be considered to be the factor determining the molecular shape at greater distances, which can help in both predicting the interactions with the receptor at the stage of remote recognition and in finding the preferred directions of solvation by a polar solvent. In the analysis of the fields three techniques have been used: (i) the construction of maps in certain planes; (ii) the construction of maps on spheres centered in the charge center of the molecule under study and of poles chosen according to the main axes of the quadrupole moment; and (iii) the construction of surfaces corresponding to a given value of potential. The results obtained show that the shapes of both MEP and MEF are similar in the case of [Mpa1]-AVP and [Cpp1]-AVP (biologically active), while some differences emerge when comparing these compounds with [Ths1]-AVP (inactive). It has also been found that both MEP and MEF depend even more strongly on conformation. PMID- 2585003 TI - The Gold Rush of '89. PMID- 2585005 TI - A study of the self-perception of being overweight in adult inhabitants of Cracow. AB - The self-assessment of body weight (normal vs overweight) reported in an interview in a group of 783 men and 1085 women aged 32-83, was compared with weight and height measurements taken a few days after the interview. Among subjects with body mass indices revealing excess weight (over 27 kg/m2 in men and 45 kg/m in women), 24% of men and 15% of women reported having normal body weight. The proportion of overweight persons unaware of their condition was related to age, smoking habit, education and physical activity. In men with hypertension, the proportion of subjects unaware of being overweight was smaller by 25% compared with others. This was not the case in women. A history of cardiovascular disease, diabetes, dyspnea or poor health status had no effect on the awareness of being overweight. PMID- 2585004 TI - Quality of life activities associated with adherence to insulin infusion pump therapy in the treatment of insulin dependent diabetes mellitus. AB - The impact of continuous subcutaneous insulin infusion (CSII) pump therapy on patients' activities of daily living and the prevalence of acute complications were examined in order to characterize patients' experience while on CSII, and to ascertain whether any of these factors could be associated with continued use of CSII. Fifty-one of 55 patients (93%) identified as initiating CSII in our medical center patient population completed retrospective surveys; 37 individuals (73%) were still using pumps and 14 individuals (27%) had discontinued pump use. CSII appeared to affect the quality of daily activities only modestly, neither improving nor interfering with many activities to any great degree. Activities associated with greatest improvements were eating, working, traveling, sleeping, and exercising. Results of logit analyses adjusting for duration of pump therapy indicated that the prevalence of six different acute complications (skin infections at the needle site, mild insulin reactions, more severe insulin reactions requiring assistance, hypoglycemic coma, asymptomatic hypoglycemia, and ketoacidosis) was not statistically associated with patients' decisions to continue or to stop CSII. In contrast, significant differences (p less than 0.05) between the groups continuing and discontinuing CSII were found in 11 of 18 activities of daily living. In general, patients continuing CSII, in contrast to those discontinuing CSII, found that many of their activities were improved significantly during pump therapy. There were few differences between groups in the degree to which CSII was perceived to interfere with daily activities. However, those continuing CSII found it significantly less necessary to take the pump off while doing some activities than did those discontinuing CSII.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585006 TI - An integrative framework for health-related research. AB - Research on the manifold aspects of health and health-care delivery, economics and administration has expanded rapidly in recent years and now engages a number of disciplines. The array of theories, methods, and analytical strategies derived from such diverse sources frequently impedes effective communication between investigators and sometimes renders it impossible. We propose a conceptual framework that encompasses all health-related research and demonstrates the relationships and interfaces between the various disciplines involved. The framework emerges from a classification of health-related research into studies of health states or health interventions followed by consideration of the level of analysis (e.g. cell, individual, community) employed and the purpose of each study (development, description, explanation, or evaluation). PMID- 2585007 TI - A prospective study of the reliability and convergent validity of three physical activity measures in a field research trial. AB - This investigation sought to determine the test-retest reliability and convergent validity of three commonly used physical activity measures. The Stanford Physical Activity Recall, the Caltrac Activity Monitor, and a daily physical activity log were administered to 45 subjects over a 3-week period. The results indicated high levels of test-retest reliability for the Stanford and the daily log; low test retest reliability was obtained for the Caltrac. Convergent validity was also high between the Stanford and daily log but was low for both of these measures with the Caltrac. These results suggest that the Stanford Physical Activity Recall may be the self-report measure of choice for large studies due to its high reliability and convergent validity with a more time-consuming daily log, as well as its cost- and time-efficiency. Based on the results, it is recommended that the Caltrac activity sensors not be used for field studies of physical activity until the logistical problems of their use in clinical trials are solved. PMID- 2585008 TI - Recurrence of low birth weight in siblings. AB - The recurrence of low birth weight (LBW, less than 2500 g) in full siblings was studied in 3286 singleton infants born between 1966 and 1986 to 1677 male U.S. Army veterans who were part of a nationwide health study. Hospital of birth medical records were abstracted for these children. Mean birth weights, risks of LBW, LBW occurring with preterm delivery (less than 37 weeks) (LBW/p), and LBW in term infants (LBW/t) were examined in successive singleton siblings according to LBW status of prior siblings. The risk of LBW in infants who had prior siblings with LBW was 9.9%, compared with a risk of 2.8% in infants who had prior siblings without LBW (OR = 3.8, 95% CI 2.0-7.3). The excess recurrence of LBW was specifically due to LBW/p. Infants with prior siblings with LBW/p were at high tisk of LBW/p (OR = 9.2, CI 4.4-19.6) but not of LBW/t (OR = 2.0, CI 0.1-9.1). Using modified logistic regression techniques that incorporate familial risks and the effects of other risk factors, the excess sibling recurrence risk of LBW and LBW/p could not be explained by the tendency for recurrence in siblings of other risk factors for LBW, such as pregnancy complications, maternal illnesses, and birth defects. Although the familial factors involved in LBW may or may not be genetic in nature, such factors need to be investigated in epidemiologic studies of LBW and prematurity. PMID- 2585009 TI - Behavior of the exposure odds ratio in a case-control study when the hazard function is not constant over time. AB - In case-control studies of adverse drug effects there is rarely much evidence to support the assumption that the hazard function among users is constant during therapy. Nonetheless, this assumption is often implicitly made. We will use both clinical reasoning and a simple model to show how non-constancy of the hazard function affects odds ratio interpretation. When the hazard function is non constant and there is more than one temporal pattern of drug usage, the odds ratio will estimate a weighted mean of incidence ratios with weights dependent on the corresponding fractions of person-time. If the duration-specific incidence ratios differ widely, the odds ratio will depend not only on the drug but also on its usage pattern in the study population. This may explain some of the large regional odds ratio variation for dipyrone-related agranulocytosis in the International Agranulocytosis and Aplastic Anemia Study (JAMA 1986; 256: 1749 1757. PMID- 2585011 TI - A comparison of interview data and medical records for previous medical conditions and surgery. AB - Although interview information is usually the sole source of data in case-control studies, the accuracy of such data is infrequently assessed. We compared interview data on selected medical conditions and surgical procedures with medical records of subjects with chronic lymphocytic leukemia. We examined agreement by type of respondent (self or surrogate), age, sex, race, and type of hospital. The strength of agreement between the two data sources (as measured by kappa statistics) was substantial kappa greater than 0.6) for splenectomy, appendectomy, asthma, and systemic lupus erythematosus; moderate kappa greater than 0.4) for tonsillectomy/adenoidectomy, tuberculosis, diverticulitis, hepatitis, rheumatic fever, and drug allergy; and poor kappa less than 0.3) for chronic bronchitis, chronic sinusitis, psoriasis, rheumatoid arthritis, and most other types of allergy. In general, self respondents had more accurate recall than surrogate respondents. Among self respondents the strength of agreement tended to be greater for males than females, for whites than blacks, and for subjects from referral hospitals than for community hospitals. No consistent patterns were apparent by age. Despite a number of limitations, the findings of the study provide an addition to the scant epidemiologic literature on this topic, and suggest that for certain conditions medical record data collection may be needed to supplement interview information. PMID- 2585010 TI - Risk adjustment in claims-based research: the search for efficient approaches. AB - Claims-based indices of comorbidity and severity, as well as other measures derived from routinely collected administrative data, are developed and tested. The extent to which risk adjustments using claims can be improved by adding information from one well-known measure based on chart review and patient examination (the American Society of Anesthesiologists' (ASA) Physical Status score) is also examined. Readmissions and mortality after three common surgical procedures are the outcomes studied using multiple logistic regression. Claims based measures of comorbidity, derived both from hospital discharge abstracts at the time of surgery and from hospitalizations in the 6 months before surgery, provided reasonably good predictions of postsurgical readmissions and mortality. In the most complete logistic regression models, the Somers' Dyx measure of fit (a rank correlation coefficient) ranged from 0.23 to 0.38 for readmissions and from 0.46 to 0.72 for mortality. In 5 out of 6 cases, these predictions were not improved by including the prospectively-collected ASA Physical Status score. Such difficulties in improving risk adjustment by more intensive data collection are discussed in terms of their research implications. PMID- 2585012 TI - Predictors of disability in elderly Finnish men--a longitudinal study. AB - Factors predicting disability in late life were studied in 716 men from eastern or southwestern Finland in connection with the 25-year follow-up of the East-West Study, which is part of the Seven Countries Study, in 1984. In middle-aged men, low forced vital capacity, occurrence of diabetes, presence of intermittent claudication, high diastolic blood pressure, higher age and lower educational level showed the greatest predicting power for future disability 15-25 years later. In later middle age, low forced vital capacity, presence of intermittent claudication, cerebrovascular disease or coronary heart disease and higher age were the most powerful predictors for disability 10 years later. In order to lower disability in old age, it is important to prevent deterioration of ventilatory function and cardiovascular diseases in middle-aged populations and to treat chronic diseases adequately. PMID- 2585014 TI - Screening for HIV: can we afford the confusion of the false positive rate? PMID- 2585013 TI - Characteristics of reproductive life and risk of breast cancer in a case-control study of young nulliparous women. AB - Between 1982 and 1985, a case-control study of nulliparous women, aged 25-45, was conducted to analyse the relationships between the risk of breast cancer and causes of nulliparity, including contraceptive methods. Fifty-one cases of breast cancer diagnosed less than 3 months before interview were matched with 95 controls on age at diagnosis, year of interview, and medical center. The causes of nulliparity related to female sterility or subfertility (mechanical or hormonal disorders) were not found to be associated with a significantly higher risk of breast cancer. The causes related to fertilization failure, i.e. no sexual partner, rare sexual intercourse (less than once per month), or partner with abnormal semen, were found to lead to an increased risk. Detailed analysis of contraceptive methods showed that the risk of breast cancer increased (p = 0.02) with a longer duration of use of barrier methods (withdrawal or condom). Conversely, the risk significantly decreased (p = 0.004) with a longer duration of use of non-barrier methods (oral contraceptives, IUD, cap, local spermicides, vaginal douche, safe period, or no method), i.e. methods allowing a direct exposure to human semen. PMID- 2585015 TI - Quality of life instruments for cancer patients: "Babel's Tower revisited". PMID- 2585016 TI - Fluorouracil, interferon-alpha, and colon cancer: rational pursuit of synergism between antimetabolites and biologicals. PMID- 2585017 TI - How much MOPP? PMID- 2585018 TI - Fluorouracil and recombinant alfa-2a-interferon: an active regimen against advanced colorectal carcinoma. AB - Based on in vitro studies that have demonstrated synergy between recombinant alfa 2a-interferon (rIFN alpha-2a) and the fluoropyrimidine, fluorouracil (5FU), against two human colon cancer cell lines, a pilot clinical trial was initiated to determine the effects of the combination of 5FU and rIFN alpha-2a in patients with advanced, unresectable colorectal carcinoma. A total of 30 patients were enrolled; all were evaluable. 5FU was administered as a loading course, 750 mg/m2 daily for 5 days by continuous infusion followed by weekly bolus therapy, rIFN alpha-2a, 9 MU, was administered subcutaneously three times per week. Of 17 previously untreated patients evaluable for response, 13 achieved a response. Three patients had disease progression. No previously treated patients had a major response. There was one death clearly related to therapy, an event preceded by watery diarrhea and neutropenic sepsis. Other toxicities were reversible and responded to dose reduction. With a median follow-up of 16+ months, median survival has not been reached among the previously untreated patient cohort. We conclude that the combination of 5FU and rIFN alpha-2a is an active regimen against disseminated colorectal cancer in previously untreated patients. PMID- 2585019 TI - Dose intensity of MOPP chemotherapy and survival in Hodgkin's disease. AB - The association between dose intensity of chemotherapy with the rate of complete remission (CR), the duration of disease-free survival (DFS), and overall survival (OS) was separately analyzed for 67 patients initially treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), and for 75 patients in relapse following radiotherapy who had received MOPP as a salvage regimen. In both groups of patients, the fraction of the total dose of mechlorethamine delivered in all cycles divided by the planned dose for six cycles was strongly associated with OS (P = .002 for patients receiving initial MOPP and P = .02 for the salvage group, respectively). B symptoms were independent of drug-derived variables associated with OS (corresponding P values .03 for initial MOPP and .004 for the salvage group). The predictive value of mechlorethamine dosage with regard to OS was retained in an analysis restricted to the patients receiving greater than or equal to six cycles of chemotherapy. In the initial chemotherapy group, mechlorethamine dosage was associated with attainment of CR but none of the variables tested was predictive of DFS. In the salvage chemotherapy group, mechlorethamine dosage was associated with attainment of CR and duration of DFS as well. The results emphasize that, besides tumor characteristics, optimal dosage of chemotherapy is of great importance for survival. PMID- 2585020 TI - Clinical significance of immunophenotype in diffuse aggressive non-Hodgkin's lymphoma. AB - We performed a prospective study of the clinical significance of immunophenotype in 110 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by oncologists in the Nebraska Lymphoma Study Group between October 1982 and May 1986. All patients were immunophenotyped from biopsies performed before therapy was administered. The patients were treated with a uniform protocol of radiotherapy for minimal nonbulky, stage I or II disease (seven patients) or a single, six-drug chemotherapy regimen cyclophosphamide, doxorubicin, procarbazine, bleomycin, vincristine, and prednisone (CAP-BOP) in patients with more extensive disease (103 patients). Ninety-one patients (83%) had B-cell lymphoma and 19 patients (17%) had T-cell lymphoma. The histologic diagnosis of diffuse mixed-cell lymphoma was significantly associated with T-cell immunophenotype (45% v 5%; P less than .001), and the diagnosis of diffuse large cell lymphoma was significantly associated with B-cell immunophenotype (40% v 5%; P = .006). However, no significant difference in frequency of prognostic variables such as age, stage, systemic symptoms, tumor bulk, serum lactic dehydrogenase, or performance status was found between the B-cell and T-cell groups. Patients with B-cell NHL had a slightly higher complete remission rate (74% v 53%; P = NS), similar durability of complete remission (75% v 70% at 3 years; P = NS), and a slightly but not significantly better overall survival (50% v 41% at 3 years; P = NS). The slight advantage in response rate and survival for B-cell patients was related to a very poor outcome for patients with stage IV T cell NHL. For patients with stage I to III disease, neither the complete remission rate (B-cell, 82% v T-cell, 91%; P = NS) nor overall survival (3-year survival for B cell, 58% v T cell, 73%; P = NS) were significantly different. However, with stage IV disease B-cell patients fared far better than those with T cell NHL for both complete remission rate (67% v 0%; P = .002) and overall survival (3-year survival, 44% v 0%; P = .002). Immunophenotyping intermediate- and high-grade NHL allowed identification of a subgroup of patients who had a very poor prognosis with this treatment approach and for whom alternate therapy might be considered. PMID- 2585021 TI - High frequency of benign mediastinal uptake of gallium-67 after completion of chemotherapy in children with high-grade non-Hodgkin's lymphoma. AB - We observed increased gallium-67 uptake in the mediastinum after completion of chemotherapy in 10 of 62 patients with non-Hodgkin's lymphoma. All 10 were under 15 years of age, yielding a frequency of 43% in this age group. The interval between cessation of chemotherapy and the development of increased gallium-67 uptake ranged from 1 to 8 months, and the abnormality persisted for 2 to 59 months. Serial chest x-rays were performed in all patients, and four of the 10 had transient widening of the mediastinum that remained within normal limits for the children's ages. Three patients had chest computed tomographic (CT) scans at the time of increased gallium-67 uptake, and one of the three had serial scans that showed a mediastinal mass consistent with thymic enlargement. All of the patients were asymptomatic and none were biopsied. All 10 remained well, with a mean follow-up of 52.5 months. The phenomenon we describe is probably due to "rebound" thymic hyperplasia, which is a benign and transient condition. We conclude that abnormal mediastinal gallium-67 uptake after completion of chemotherapy is likely to be benign and transient if the patients are young, have small non-cleaved-cell histology, are without other evidence of lymphoma recurrence, and do not have initial mediastinal involvement. Progressive widening of the mediastinum on chest x-ray is cause for suspicion and requires further evaluation. Serum lactate dehydrogenase (LDH) levels may not be helpful in differentiating a benign from a malignant process. PMID- 2585023 TI - Prognostic factors in multiple myeloma: definition of risk groups in 410 previously untreated patients: a Grupo Argentino de Tratamiento de la Leucemia Aguda study. AB - Four hundred ten previously untreated multiple myeloma patients entered onto two consecutive Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) protocols were analyzed to identify significant prognostic factors influencing survival. The univariate analysis selected the following variables: performance status, renal function, percentage of bone marrow plasma cells at diagnosis, hemoglobin, and age. A multivariate analysis showed that performance status, renal function, percentage of bone marrow plasma cells, hemoglobin, and age were the best predictive variables for survival. A score was assigned to each patient according to these variables, which led to their classification in three groups: good, intermediate, and poor risk, with a probability of survival of 26% and 10% at 96 months, and 5% at 56 months, and median survival of 60, 37, and 14 months, respectively (P = .0000). In our patient population, this model proved to be superior to the Durie-Salmon staging system in defining prognostic risk groups, and separating patients with significantly different risks within each Durie Salmon stage. PMID- 2585022 TI - Variable mercaptopurine metabolism and treatment outcome in childhood lymphoblastic leukemia. AB - Intracellular thioguanine nucleotides (6-TGN) are the major cytotoxic metabolites of mercaptopurine (6-MP). Red blood cell (RBC) 6-TGN concentrations were measured in a group of 120 consecutive children with lymphoblastic leukemia (ALL) to assess interpatient variability and its clinical importance. Assays were performed after at least 2 months 6-MP maintanance chemotherapy and a minimum 7 days unattenuated protocol dose of 75 mg/m2. Observed 6-TGN concentrations ranged from 126 to 832 pmol/8 x 10(8) RBCs (median, 275). There was a correlation between 6-TGN and neutropenia 14 days postassay (rs = .51; P less than .0005), and an inverse correlation between 6-TGN and the length of time uninterrupted full protocol dose was tolerated without neutropenia (rs = -.3; P less than .01). After a median follow-up of 49 months, 19 children had relapsed, of whom 17 (89%) had 6-TGN concentrations below the group median (log-rank chi 2 = 11.9; P less than .001). Multivariate analysis using Cox's proportional hazards regression showed the 6-TGN effect on disease control to be independent of diagnostic WBC count, sex, age, immunological cell type, French-American-British (FAB) type, variation in other antineoplastic therapy, and duration of remission at the time of 6-TGN assay. Children with ALL taking the same dose of 6-MP show great variability in its measurable cytotoxic effect, and this variability is apparently important in predicting treatment outcome. PMID- 2585024 TI - Interleukin-2 induces profound reversible cholestasis: a detailed analysis in treated cancer patients. AB - Interleukin-2 (IL-2)-based immunotherapy is associated with profound reversible cholestasis and hyperbilirubinemia. We performed a nonrandomized retrospective and prospective analysis to determine the incidence, characteristics, clinical course, and nature of the IL-2-induced liver dysfunction in patients with cancer. Patients received IL-2 at a dose of 20,000 to 100,000 units (U)/kg thrice daily for up to 5 days. Fifty-one patients on adjuvant treatment protocols received a mean of 10.18 +/- 2.38 IL-2 doses and 11.67 +/- 4.16 doses were delivered to 210 patients with advanced disease during this period. Retrospective analysis of all patients receiving this therapy revealed increases in the following liver function tests expressed as median, 25th percentile, and 75th percentile (range): bilirubin (mg/dL) 4.5, 2.6, 6.5 (.4 to 38.5); alkaline phosphatase (U/L) 256, 179, 378 (56-1680); SGOT (U/L) 80, 52, 117 (18 to 483); SGPT (U/L) 91, 64, 132 (20-540); prothrombin time 13.4, 12.8, 14.5 (10.8 to 35.4); and albumin (g/dL) values decreased (trough) slightly 3.0, 2.8, 3.2 (2.3 to 3.8). Multiple regression analysis revealed several factors that were significantly associated with the increase in bilirubin when jointly considered (model P2 less than or equal to .001) including total IL-2 dosage, increase in creatinine, alkaline phosphatase, weight, and SGOT. Similar increases were noted in a prospectively evaluated group of 10 patients. A return to normal levels of bilirubin was noted within 5.6 days of stopping IL-2. Fasting serum cholylglycine increased from a mean of 32.3 +/- 1.6 to a peak of 1556.0 +/- 625.0 mg/mL. Although conventional ultrasound examinations were unrevealing, tissue ultrasound examinations revealed a mean scatterer spacing (MSS) increase compared to baseline of .10 +/- .04 (P less than .02) suggesting hepatic edema or an infiltrative process. Further, computerized hepatobiliary nuclear medicine scans revealed a delay in uptake (2.2 +/- 0.5 fold greater) and excretion (8.0 +/- 5.9 fold greater) of technetium-99m labeled disofenin. These findings support the development of profound reversible cholestasis as the primary basis for the elevated bilirubin in patients undergoing IL-2 treatment and may have implications for understanding the jaundice observed in some patients postoperatively as well as that associated with sepsis and other inflammatory disorders. Specifically, the release of IL-2 or the induction of other factors similarly induced by IL-2 may be responsible for these findings. Tissue ultrasound and computerized hepatobiliary scans provide additional noninvasive assessments of liver function and physiology. PMID- 2585025 TI - Mechanisms of bone destruction in multiple myeloma: the importance of an unbalanced process in determining the severity of lytic bone disease. AB - In order to clarify the mechanisms involved in the occurrence of lytic bone lesions (BL) in multiple myeloma (MM), we have compared the presenting myeloma induced histological bone changes of 14 previously untreated MM patients with lytic BL with those of seven MM patients lacking lytic BL at presentation despite similar myeloma cell mass. A major unbalanced bone remodeling (increased bone resorption with normal to low bone formation) was the characteristic feature of patients presenting lytic BL. Furthermore, this unbalanced process was associated with a significant reduction of bone mass. Unexpectedly, a balanced bone remodeling (increase of both bone resorption and bone formation, without bone mass reduction) rather than a true lack of an excessive bone resorption was the usual feature of patients lacking lytic BL. Our current work clearly shows that a majority (72%) of patients with MM present an important unbalanced bone remodeling at diagnosis, leading to bone mass reduction and bone destruction (unbalanced MM). Some patients (20%) retain a balanced bone remodeling with initial absence of bone destruction (balanced MM). Few (8%) patients have pure osteoblastic MM without bone destruction. PMID- 2585026 TI - A phase I study of samarium-153 ethylenediaminetetramethylene phosphonate therapy for disseminated skeletal metastases. AB - Thirty-five patients with disseminated skeletal metastases from a variety of tumor types underwent clinical trial of samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) on a day-patient basis. Individual beta radiation dosimetry was based on pharmacokinetic studies of a 20 mCi tracer dose of 153Sm-EDTMP. The retained skeletal activity varied unpredictably from 40% to 95% of the administered dose, but in all patients greater than 98% of the nonosseous activity was cleared in the urine within 6 hours. Prospective calculation of radiation dosimetry in each patient permitted an accurate dosage schedule based upon total red marrow exposure, starting at 100 cGy and escalating to 280 cGy to define the dose-limiting myelotoxicity. Pain was relieved in 22 of 34 evaluable patients (65%) for periods ranging from 4 to 35 weeks, following a single administration of 153Sm-EDTMP. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of nine patients. The dose limiting toxicity was myelosuppression manifested particularly by delayed thrombocytopenia. Platelet counts less than 100 x 10(9)/L occurred in 42% of courses when bone marrow radiation absorbed dose exceeded 200 cGy. Myelosuppression was transient and platelet counts had recovered to pretreatment levels within 10 weeks of treatment. 153Sm-EDTMP is effective for the amelioration of pain due to disseminated skeletal metastases particularly with carcinoma of breast or prostate where 83% of patients experienced pain relief. In 15 of the 34 evaluable patients there was evidence of stabilization or regression of skeletal metastases on radiographs and follow-up technetium-99m methylene diphosphonate (99mTc-MDP) bone scans. PMID- 2585027 TI - Fatal intramedular tumor of the cervical spinal cord during remission of acute lymphoblastic leukemia. AB - An adult male with acute lymphoblastic leukemia including meningeal leukemia was in complete clinical remission for more than one year after initiation of chemotherapy including intrathecally methotrexate and irradiation towards the brain and spinal cord. Signs of central nervous system involvement developed with symptoms primarily from the lower limbs and the urinary bladder but the cerebrospinal fluid was consistently without lymphoblasts. By magnetic resonance imaging an intramedular tumor of the cervical spinal cord was demonstrated and malignant cells compatible with lymphoblasts were obtained from the tumor at laminectomy. Despite immediate irradiation towards the tumor the patient died within two weeks. PMID- 2585028 TI - The intracerebral penetration of intraventricularly administered methotrexate: a quantitative autoradiographic study. AB - The local concentration and distribution of methotrexate following intraventricular administration were studied in the brains of New Zealand White rabbits. Tritiated methotrexate was injected through subcutaneous reservoirs connected to ventricular catheters, the animals were sacrificed one hour after administration of the drug, and the distribution of the radiolabelled compound was assessed using quantitative autoradiographic techniques. The intracerebral distribution of tritiated inulin delivered in an identical fashion was studied for comparison. One hour after intraventricular administration of radiolabelled methotrexate or inulin approximately 40% of the area of the brain sections contained appreciable concentrations of the radiolabelled tracer. Gray matter adjacent to the cerebrospinal fluid, including the hippocampus, thalamus, caudate nucleus, and periaquaductal gray contained the highest concentrations of 3H methotrexate. Large white matter tracts contained smaller amounts of tracer activity. The rapid and extensive penetration of intraventricularly administered methotrexate and inulin into normal brain parenchyma and the high methotrexate concentrations in specific regions of the brain provide insight into the pathogenesis of methotrexate-induced neurotoxicity. PMID- 2585031 TI - Inhibitors and inactivators of beta-lactamase from Mycobacterium fortuitum. AB - The inhibiting or inactivating effects of some beta-lactam antibiotics on beta lactamase from Mycobacterium fortuitum were studied. Among all substrates tested, clavulanic acid and sulbactam were the strongest competitive inhibitors of the enzyme although the latter was slightly hydrolyzed. Imipenem and cefoxitin scarcely inhibited the beta-lactamase yet expressed good activity against the microorganism in vitro, suggesting that the effectiveness of these drugs on M. fortuitum might be due to high permeation through the cell wall. All the isoxazolylpenicillins tested and methicillin inactivated the enzyme of M. fortuitum by a first rapid phase of acylation followed by a steady-state process of enzyme reactivation (deacylation). Clavulanic acid and sulbactam showed Ki values for the enzyme inactivation closely corresponding to hematic concentrations achievable in vivo during antibiotic treatment. PMID- 2585029 TI - Major structural alterations of the c-sis gene are not observed in a series of tumors of the human central nervous system. AB - Expression of the c-sis oncogene, the gene encoding the B chain of platelet derived growth factor (PDGF), may be related to initiation and/or progression of glial cell tumorigenesis by PDGF-mediated autocrine growth stimulation. As the mechanism for activation of expression of the c-sis gene in gliomas is not known, we searched for possible structural alterations of c-sis DNA in these tumors. Genomic Southern blots of DNA from 7 different cultured human glioblastoma cell lines and 15 different solid human brain tumors revealed no significant change in either the gross structure or the copy number of the c-sis gene in tumor cells vs. control cells. Activation of glioma c-sis gene expression is therefore not the result of a gross rearrangement or amplification of the c-sis gene. Expression of c-sis mRNA was detected in all of 12 different solid human brain tumors, 11 of which were of glial cell origin. However, in tissue adjacent to 5 different tumors, approximately the same level of c-sis mRNA was seen. PMID- 2585030 TI - Distribution of collagen type IV in brain tumors: an immunohistochemical study. AB - One hundred-twenty seven human brain tumors were examined by an immunoperoxidase technique for the expression of collagen Type IV, a major constituent of basement membrane. The parenchymal components were negative for the marker protein in all tumors except for neurilemmomas which were positively stained. In every case, the antibody to collagen Type IV showed distinct staining of the vascular pattern. In gliomas, capillaries increased in number and the vascular staining increased in intensity. Fine branching capillaries and endothelial glomeruloid proliferations characteristic each of oligodendrogliomas and glioblastomas could be distinctly illustrated. In two ependymomas, marked capillary proliferation was noted in periventricular areas. Fibrillar staining was observed between the tumor cells in seven of 34 meningiomas. Pericapillary lamellar deposition of collagen Type IV suggests a vascular origin of psammoma bodies. In some malignant tumors, pial glial membranes were disrupted and the Virchow-Robin spaces were filled with malignant cells. Collagen Type IV was absent around the stromal cells of hemangioblastomas, suggesting that these stromal cells were unrelated histogenetically with endothelial cells. Collage Type IV may be useful in the differential diagnosis between meningiomas and neurilemmomas. PMID- 2585032 TI - Treatment of Echinococcus granulosus hydatid disease with mebendazole. AB - The Authors report their personal experience in the treatment of 70 patients with hydatid cysts of different localization with mebendazole, following protocols approved by WHO. During treatment patients were submitted to careful clinical, biochemical, radiological and immunological controls. On the whole, 150 hydatid cysts and 13 cases of widespread hydatidosis were observed. Follow-up ranged from 6 months to 5 years. Morphological and/or volumetric modifications were observed in 64.3% of the total number of cysts treated, regardless of their localization. 9 relapses were observed, and all but one case showed the same previous sensitivity to a further cycle of mebendazole. The observed side effects were not severe. PMID- 2585033 TI - A comparison of two assays for the in vitro chemosensitivity testing of human acute non-lymphoblastic leukemia cells. AB - In vitro chemosensitivity of blast cells from 19 patients, affected by acute non lymphocytic leukemia, to cytosine arabinoside and daunorubicin was investigated. A semiautomated P-iodonitrotetrazolium violet (INT) colorimetric assay, based on the ability of viable cells to cleave piodonitrotetrazolium violet into a red formazan derivative and a short-term antimetabolic assay based on the uptake inhibition of [3H]-thymidine were compared in terms of their ability to predict clinical outcome. Both methods were able to discriminate between sensitive and resistant patients by in vitro cytosine arabinoside testing. On the contrary the assays carried out with daunorubicin failed to predict the clinical outcome. A good correlation was demonstrated between the results of the two different methodological approaches, validating the recently described INT sensitivity test. PMID- 2585034 TI - Skin and perivascular toxicity induced experimentally by doxorubicin. AB - Extravasation of antitumor drugs and particularly doxorubicin (DXR) can be followed by skin ulceration and slowly evolving perivascular necrosis. DXR lesions have some characteristics in common with those induced by ionizing radiation and, with respect to gross morphology, are reminiscent of skin lesions induced by necrotizing agents. Time course and histopathology of toxic phenomena induced by intradermal or perivascular injection of various doses of either DXR or caustic chemicals have been studied in hairy outbred and hairless inbred (MF1 hr/hr) mice. The latter strain has been found to be intrinsically more sensitive to DXR induced toxic effects, particularly as far as perivascular administration is concerned. Long lasting lesions and, in a few cases, systemic involvement have been observed. On the contrary, necrotic foci induced by caustic chemicals rapidly regressed in both strains. The perivascular administration model, which has not been previously investigated, appears to be representative of what happens in clinical conditions and can be of use for assessing either skin toxicity of antitumor compound or the protective effect of candidate antidotes. PMID- 2585035 TI - Phase II trial of 5-fluorouracil and high-dose folinic acid in advanced renal cell cancer. AB - Fourteen patients with metastatic renal cell carcinoma (RCC) were treated with high-dose folinic acid (HDFA): 200 mg/m2 i.v. and 5-fluorouracil (5-FU): 370 mg/m2 i.v. for 5 consecutive days every 28 days. Severe oral mucositis (WHO grade III-IV) was experienced by two patients, whereas hematological toxicity was mild. No complete or partial remission was observed. Short-lasting stable disease occurred in 8 patients (median = 5 months, range 2-11). This combination does not need further evaluation in patients with RCC. PMID- 2585036 TI - Mechanics of stretch in activated crustacean slow muscle. II. Dynamic changes in force in response to stretch. AB - 1. The mechanical dynamics of the ventral superficial muscles (VSM) of the abdomen of the hermit crab, Pagurus pollicarus, have been analyzed to develop a quantitative model of gradedly excitable arthropod muscle. Such a model is important for understanding the role of proprioceptive reflexes in posture and movement. 2. The decay in force produced after ramp stretch of both passive and active muscle was approximated by the use of regression equations involving a direct term and one to three exponential terms. A second-order equation produced an acceptable description of this decay over short (0.5 s) sampling durations. 3. The rate constants of the regression equation did not vary with stretch length, velocity, or activation level of the muscle. For the two-exponential-term model, the rate constants were approximately 90 and 9 s-1 for a sample duration of 0.3 s. An additional rate constant of approximately 1 s-1 was needed to adapt the model to longer sample times. 4. The direct term and the middle-order (9 s-1) residual were both functions of stretch length and activation level. The high order (90 s-1) residual was primarily a function of stretch length and velocity. Transfer functions omitting the velocity dependence adequately described the mechanical dynamics of the muscle for physiological ranges of stretch velocity. 5. White-noise length perturbations were used to calculate spectral density functions of muscle force and length. These measurements confirmed the principal observations of the ramp stretch analysis: the frequency response of the muscle was independent of the level of activation; the magnitude of the stiffness increased over the stretch frequency range of 4-40 Hz and was then almost constant; and the phase response of the muscle became slightly positive over the same range of stretch frequency. 6. The speed of activation of the muscle to different stimulus frequencies was estimated by fitting a single exponential equation to the rise in isometric tension at the onset of stimulation of the motor nerve. The rate constant increased with stimulus frequency, but its maximum value was only 1.8 s-1, about one-fourth of the middle mechanical rate constant. 7. Because muscle activation is slower than the mechanical dynamics, it is unlikely that the nervous system can regulate muscle dynamics. However, it is possible that mechanical impedance could be regulated to maintain a desired time averaged value. PMID- 2585037 TI - Encoding of nociceptive thermal stimuli by diffuse noxious inhibitory controls in humans. AB - 1. It has previously been shown that, in normal humans, heterotopic painful thermal conditioning stimuli induce parallel increase in the thresholds of a spinal nociceptive flexion reflex (RIII reflex) and the concurrent sensation of pain elicited by electrical stimulation of the sural nerve. On the basis of analogous animal studies, we proposed that such phenomena could be related to diffuse noxious inhibitory controls (DNIC), which have been described in the rat. The present study, which was carried out on normal volunteer subjects, was particularly concerned with the extent and temporal characteristics of the depressive effects of DNIC triggered by painful thermal stimuli on RIII reflex activity. In addition, because it was possible that these depressive effects could have resulted from a direct postsynaptic inhibition of motoneurons, a second part of the study was aimed at determining whether or not the heterotopic noxious thermal stimuli also affected the excitability of alpha-motoneurons, as monitored by the monosynaptic Hoffmann reflex (H reflex) technique. 2. In the 11 subjects under study, application of moderate, nonnoxious temperatures (40-44 degree C) to the contralateral hand (via a thermoregulated and agitated waterbath) did not modify the RIII reflex nor the associated sensation of pain. By contrast noxious temperatures clearly depressed the RIII reflex and the concurrent sensation of pain, both during and after the conditioning procedure (CP), in a direct linear relationship to the temperature of the waterbath in the 45-47 degree C range; the maximal depressive effect was observed with the highest conditioning temperature. A significant relationship was also found between the extent of the RIII depression during the CP and that during a 10-min period of post-CP observation. 3. The depressive effects observed on both the RIII reflex and pain were not associated with clear change in autonomic functions. Respiration remained stable during the sessions, with no significant relationship between the temperatures of the waterbath and respiratory rate. Heart rate was slightly but significantly increased during the immersion of the hand in the 46 or 47 degree C waterbaths; this increase, however, ceased with the end of CP. 4. Application of thermal conditioning stimuli produced a slight but nonsignificant increase of the monosynaptic H reflex during the first minute of CP, no matter what was the temperature of the waterbath. However, there were no subsequent variations during the 6-min period of post-CP observation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2585038 TI - Response properties in the dorsal lateral geniculate nucleus of the adult cat after interruption of prenatal binocular interactions. AB - 1. Single-cell recordings were made in the magnocellular layer of the dorsal lateral genicule nucleus (dLGN) of five adult cats in which prenatal binocular interactions were interrupted by monocular enucleation at known gestational ages. Three cats (early enucleates) had one eye removed on either embryonic day 44.48, or 49, before retinogeniculate inputs are segregated into uniocular layers. Two other (late enucleates) underwent this procedure on embryonic days 55 and 58, when segregation is well advanced. Responses were compared with those obtained from recordings in the A and A1 layers of the dLGN of seven normal adult cats. 2. Cells were classified as ON or OFF by the use of spots of light and as X or Y based on a test of linearity of spatial summation with the use of counterphased sinusoidal gratings. Receptive-field size and spatial resolution were also obtained. 3. The dLGN of prenatally enucleated cats contains a dorsal magnocellular layer and a ventral parvocellular layer. In early enucleates, only an occasional hint of a cell-sparse interlaminar zone was apparent, located between the magnocellular and parvocellular layers. In late enucleates, a prominent cell-sparse band was observed contralateral to the remaining eye, in a region that would most likely correspond to layer A1 in the normal dLGN. No such cell-sparse band was seen ipsilateral to the remaining eye in late enucleates. 4. Eighty-six X cells and 22 Y cells were studied in the enucleates. Both cell types were found at all depths of the magnocellular layer. All but a few neurons had concentric ON-center or OFF-center receptive fields that were normal in size. The topography of receptive fields also appeared normal. In addition, spatial resolution of X and Y cells was similar in experimental and control animals. 5. In early enucleates there was a higher percentage of X cells and a lower percentage of Y cells than normal. The change in X-to-Y ratio was shown to be because of both a gain in cells with X properties and a loss of cells with Y properties. The distribution of dLGN somal sizes in the early enucleates was comparable with controls, so the change in X-to-Y ratio most likely did not result from an electrode sampling bias. It was suggested that the X-to-Y ratio difference could stem from the abnormalities in retinogeniculate terminal arbors that have been shown to follow early eye removal.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2585039 TI - Intracellular recording of identified neostriatal patch and matrix spiny cells in a slice preparation preserving cortical inputs. AB - 1. The morphology, electrical membrane properties, and corticostriatal excitatory postsynaptic potentials (EPSPs) of two groups of neostriatal projection cells, patch cells, and matrix spiny cells were compared in the rat by the use of an in vitro slice preparation that preserves inputs from medial agranular cortex. Spiny cells were stained intracellularly with biocytin and identified as belonging to the patch (striosomal) compartment or to the matrix by immunohistochemistry for the 28 kD calcium-binding protein calbindin on the same sections. 2. Patch and matrix neurons had very similar axonal and dendritic morphology. Both patch and matrix cells extended their dendrites and local axon collaterals almost exclusively in their respective compartments. Patch cells and most matrix cells had local axon collaterals within or near the parent dendritic domain. However there was a class of matrix cells that extended axon collaterals over a much wider portion of the neostriatum but still restricted to the matrix compartment. 3. Input resistance and membrane time constant were estimated from the membrane response to intracellularly applied current pulses. The average values of matrix cells were and 8.41 ms. The values of patch cells were 31.8 M omega and 8.19 ms and were within the range of those of matrix cells. Both types of cells showed the same kinds of membrane nonlinearities when tested with the use of current pulses. Input resistance and time constant were both strongly affected by a fast anomalous rectification and were thus voltage-dependent, decreasing with membrane polarization. Slow ramplike depolarizing responses were observed in response to depolarizing current steps. 4. Repetitive firing was examined with the use of depolarizing current pulses. In both types of spiny cells, trains of action potentials showed little adaptation of spike frequency and linearly increased with current intensities less than 1 nA. The slopes frequency, calculated from the first and second intervals, were 115.0 and 107.2 Hz/nA, respectively, for matrix cells and 86.0 and 82.8 Hz/nA for patch cells. 5. Stimulation of the medial agranular cortex induced EPSPs in some striatal cells in both compartments. EPSP in matrix cells often showed both short-latency and long latency components, corresponding to two early components of the response observed in vivo. Some matrix cells, and all patch cells, showed only the longer latency EPSP component. The average latency was 6.3 ms in matrix cells and 9.1 ms in patch cells. The relationship between EPSP amplitude and membrane potential was nonlinear, with EPSP amplitude and duration increasing with decreasing membrane polarization.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2585040 TI - Behavioral inspiratory inhibition: inactivated and activated respiratory cells. AB - 1. Eleven adult cats were trained to stop inspiration in response to a conditioning stimulus. The conditioning stimuli were presented at the onset of inspiration at intervals of approximately 20-30 s. Intratracheal pressures, diaphragmatic activity, and the extracellular activity of single medullary respiratory neurons were recorded while the animals performed this response. 2. Inactivation of the diaphragm to the conditioning stimuli occurred at latencies that varied from 40 to 110 ms and averaged 74 +/- 32 (SD) ms. 3. The subjects of this report are 38 inspiratory neurons that were inactivated and 19 cells that were activated when inspiration was stopped behaviorally. These cells were located in the region of n. ambiguus and the ventrolateral n. of tractus solitarius. 4. The inspiratory cells that were inactivated behaviorally had the following characteristics: 1) Most had an augmenting inspiratory profile with (n = 14) or without (n = 9) postinspiratory activity. Other types were inspiratory throughout (n = 5), decrementing inspiratory (n = 3), tonic inspiratory (n = 4), early inspiratory (n = 2), and expiratory-inspiratory (n = 1). 2) Their mean discharge rate was 39 +/- 2.7 (SE) Hz. 3) The latency of their inactivation in response to the task averaged 81 +/- 4.9 (SE) ms, and 4) Their activity corresponded closely to breathing not only during the behavioral response but also during eupnea (eta 2 = 0.62 +/- 0.04, mean +/- SE) and respiratory acts such as sneezing, sniffing, meowing, and purring. 5. The cells that were activated when inspiration was stopped behaviorally had the following characteristics. 1) As a group, they had discharge profiles related to every phase of the respiratory cycle. 2) They were recorded in the same region as, and often simultaneously with, respiratory cells that were inactivated. 3) Their activity patterns were highly variable such that the signal strength and consistency of the respiratory component of that activity were weak (eta 2 = 0.27 +/- 0.03, mean +/- SE). 4) The latency of their activation in response to the task averaged 58 +/- 2.7 (SE) ms and was significantly shorter than the latency of inactivation of the high eta 2 valued inspiratory cells. 5) This activation was intense and prolonged. 6. It is hypothesized that the activated cells integrate nonrespiratory and respiratory inputs and act to inhibit other respiratory cells during the behavioral inhibition of inspiration. PMID- 2585041 TI - Responses of pigeon horizontal semicircular canal afferent fibers. I. Step, trapezoid, and low-frequency sinusoid mechanical and rotational stimulation. AB - 1. The horizontal semicircular canals of anesthetized (barbiturate/ketamine) pigeons were stimulated by rotational and by mechanical stimulation. 2. The mechanical stimulation consisted of making a small (less than 1 mm) fistula in the lateral part of the bony horizontal semicircular canal and, after inserting a probe coupled to a piezoelectric micropusher through the fistula, providing controlled indentation of the exposed membranous horizontal semicircular duct. 3. Extracellular action potentials from single horizontal semicircular canal primary afferent (HCA) fibers were recorded during sinusoidal rotational and during step, ramp, and sinusoidal mechanical stimulation. 4. The mean spontaneous discharge rate of 160 horizontal canal afferents was 86 +/- 4 (SE) spikes/s. This rate was not significantly different from that reported previously for pigeon HCA fibers recorded with the horizontal canal intact (i.e., no fistula introduced). 5. Sinusoidal mechanical indentation of the horizontal semicircular duct produced clearly entrained action potentials on 36 HCA fibers for a range of peak displacements from +/- 0.5 to +/- 30 microns. Action potentials were never modulated on afferents (n greater than 100) identified as innervating the anterior and posterior semicircular canals or the otolith organs during mechanical stimulation of the horizontal semicircular canal, even for displacements as large as 30 microns. 6. Intensity functions relating peak firing frequency (spikes per second) and peak probe displacement (micrometers) for 1.0 Hz sinusoidal mechanical stimulation were linear over the range 1.0-5.0 microns. The most sensitive units (6/36, 17%) showed response saturation as the stimulus magnitude was extended to 7 microns and beyond. 7. In 15 of 36 units, both mechanical and rotational sinusoidal stimulation (1.0 Hz) were applied to the same unit. The duct indentation magnitudes were 1.0, 2.5, 5.0, and 7.0 microns and the rotational velocities were 5, 10, and 20 deg/s. The constant of proportionality found to equate the peak response produced by rotational to that elicited by mechanical stimulation was 7.0 deg.sec-1/1.0 microns. 8. Bode plots and best-fit transfer functions of the frequency response (0.05-10.0 Hz) of 14 HCAs exposed to both mechanical and rotational stimulation were nearly identical. 9. Parameters for best-fit transfer functions, responses to step, and trapezoidal duct displacements were in excellent agreement with previous rotational studies carried out using the pigeon. 10. Although the mechanisms by which focal identation of the horizontal membranous duct produce responses have not yet been determined, primary afferent responses using this method of stimulation are directly comparable with rotatory stimulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2585042 TI - Responses of pigeon horizontal semicircular canal afferent fibers. II. High frequency mechanical stimulation. AB - 1. The horizontal semicircular canals of anesthetized (barbiturate/ketamine) pigeons were mechanically stimulated by the use of a piezoelectric micropusher that provided controlled indentation of the surgically exposed membranous horizontal semicircular duct. 2. Extracellular action potentials from single horizontal semicircular canal afferent (HCA) fibers were recorded during sinusoidal mechanical stimulation. This method of stimulation was shown in the companion paper to produce equivalent responses to those produced by rotation for frequencies ranging from 0.01 to 10 Hz. 3. Sinusoidal mechanical stimulation produced clearly entrained action potentials in some HCA fibers up to a frequency of 400 Hz (highest stimulus frequency tested), with stimulus probe displacements of +/- 1.0 and +/- 2.5 microns. Thirty-four HCA fibers were thoroughly studied. 4. For most HCA fibers, the number of action potentials per stimulus cycle decreased as stimulus frequency increased, until only one action potential per stimulus cycle was elicited. The point at which only one spike per stimulus cycle was observed was dependent on both the fiber's resting mean discharge rate (MDR) and the fiber's coefficient of variation (CV) obtained during the MDR. 5. Dynamic response properties of individual HCA fibers were found to be correlated with the fiber's CV and the resting level MDR. Neurons with lower CV values had less adaptation, higher short time constants, and lower high corner frequencies than did neurons with high CV values. For a given CV class of HCA fibers, neurons with higher MDRs had more enhanced gains and more advanced phase shifts at high stimulus frequencies than did neurons with lower MDRs. 6. Transfer function parameters affecting the dynamics of the high-frequency response were derived from the mean gain and phase shift values of regular-, intermediate-, and irregular-firing HCA fibers. Best-fit short time constant (tau S) values of 4.6, 1.9, and 2.0 ms; hair cell membrane time constant (tau M) values of 10.3, 13, and 7 ms; excitatory postsynaptic membrane time constant (tau E) values of 0.8, 0.4, and 0.5 ms; and synaptic delay time constant (tau D) values of 0.5, 0.5, and 1.4 ms were determined for regular, intermediate, and irregular classes of HCA fibers, respectively. 7. The values of 4.6, 1.9, and 2.0 ms derived for the regular, intermediate, and irregular afferents would suggest upper-corner frequencies of 35, 84, and 80 Hz for these classes of HCA fibers, respectively. PMID- 2585043 TI - Chemically and electrically coupled interneurons mediate respiratory pumping in Aplysia. AB - 1. Respiratory pumping in Aplysia consists of synchronous, brief contractions of the mantle organs that can occur spontaneously and also can be triggered by tactile or noxious stimulation. It has been shown previously to be driven in part by a cluster of electrically coupled interneurons, called the L25 cells, located in the left hemiabdominal ganglion. This paper describes a second class of interneurons, the R25 cells, that also plays an important role in the control of respiratory pumping. 2. The R25 cells are a cluster of approximately 14 interneurons located in the right hemiabdominal ganglion, roughly symmetrical to the L25 cells. The R25 cells are electrically coupled to each other and to the L25 cells. Some R25 and L25 cells also produce chemically mediated fast excitation and slow inhibition of other neurons in the R25/L25 network. 3. Three lines of evidence demonstrate that the R25 cells play a role in mediating respiratory pumping: 1) They fire in a synchronous burst each time the behavior occurs. 2) They make direct chemical synaptic connections to motoneurons that mediate the behavior; and 3) Firing a single R25 cell can trigger the entire behavior, by recruiting synchronous bursts of activity in all of the other R25 and L25 neurons. Individual R25 and L25 cells can act both as trigger cells (exciting the other interneurons) and as relay cells (projecting directly to motoneurons). 4. Burst initiation within the R25/L25 network appears to have two phases: 1) There is an initial phase when the R25 and L25 cells fire at a relatively low frequency. This phase can be driven either by endogenous pacemaker activity of the R25/L25 cells or by afferent synaptic input from sensory pathways; and 2) The late, high-frequency phase of the burst results largely from reverberation within the network, as activity in each cell contributes positive feedback via the excitatory chemical and electrical connections between R25 and L25 cells. 5. Synchronization of the different motor outputs that make up the pumping behavior is achieved by three mechanisms: 1) When pumping occurs spontaneously, the electrical coupling between the cells of the R25/L25 network ensures that these cells will all be near spike threshold at the end of each interburst period.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2585044 TI - Corticomotoneuronal postspike effects in averages of unrectified EMG activity. AB - 1. Spike-triggered averaging (SpTA) of rectified electromyograms (EMGs) in awake monkeys is recognized as an effective means of establishing causal relations between cortical/cell discharge and muscle activity. The appearance of postspike facilitation (PSF) in averages of rectified EMG activity is interpreted as evidence of an underlying excitatory synaptic linkage between the trigger cell and motoneurons. Cells producing PSF are referred to as corticomotoneuronal (CM) cells. Similarly, postspike suppression (PSS) is interpreted as evidence of underlying inhibitory synaptic linkages. Studies to date have focused almost exclusively on averages of full-wave rectified EMG activity. Because the potential utility of SpTA of unrectified EMG activity has not been systematically examined, we compared postspike effects in SpTAs of rectified and unrectified EMGs for 44 cortical cells yielding 293 cell-target muscle pairs (CMPs). 2. Clear PSF was found in 110 of 293 averages of rectified EMG activity from 28 known CM cells. Forty-nine of these 110 CMPs (45%) also showed clear postspike effects (PSE) in the corresponding averages of unrectified EMGs activity. Loss of effects in averages of unrectified EMGs can be attributed to cancellation of the negative and positive phases of motor unit potentials. Mean onset latencies were similar for effects in rectified and unrectified EMGs [6.9 +/- 1.8 (SD) ms vs. 6.6 +/- 1.2 (SD) ms]. Overall, the magnitudes of effects measured as peak-to-noise ratios were also similar for effects in the two groups (8.8 vs. 8.7). The 61 CMPs that showed clear PSF in rectified EMGs but no effects in corresponding unrectified EMGs had, as a group, longer and more dispersed onset latencies and were weaker in magnitude than those that showed effects in both rectified and unrectified EMGs. Moreover, the occurrence of clear effects in averages of unrectified EMGs was correlated with the strength of PSF (75% of strong but only 29% of weak PSFs showed clear PSEs in averages of unrectified EMG activity). 3. Clear PSS was observed in 24 (8%) averages of rectified EMGs derived from nine cells. Remarkably, clear PSEs were found in 12 of the corresponding averages of unrectified EMG activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2585045 TI - Spatiospectral properties of goldfish retinal ganglion cells. AB - 1. Responses of single ganglion cells from isolated goldfish retinas were recorded during presentation of various spatial and spectral stimuli. Each cell was classified along several spatial [spatial summation class, spatial contrast sensitivity function (CSF), and response to contrast] and spectral (Red-ON, Red OFF or Red-ON/OFF, and spectral opponency/nonopponency) dimensions. 2. Linearity of spatial summation was determined from responses to contrast-reversal sinusoidal gratings positioned at various locations across the receptive field of the cell. CSFs were derived from responses to sinusoidal gratings of various spatial frequencies and contrasts, drifting across the cell's receptive field at a rate of 4 Hz. Response to contrast was determined from responses to variations in contrast of a sinusoidal grating of optimal spatial frequency. Spectral classifications were based on responses to monochromatic stimuli presented separately to the center and surround portions of the receptive field. 3. Linearity of spatial summation (X-, Y-, and W-like) was independent of the cell's spectral properties; for example, an X-like cell could be classified as either a Red-ON, Red-OFF, or Red-ON/OFF center cell and as spectrally opponent or nonopponent. 4. There were differences in response to contrast across spectral categories. Red-OFF center cells were very sensitive to contrast compared with Red-ON center cells. Spectrally nonopponent cells were more responsive to contrast than spectrally opponent cells. 5. There were dramatic differences across the spectral categories in relative sensitivity to low spatial frequency stimuli; however, the spatial resolution (i.e., sensitivity to high spatial frequencies) of each spectral classification appeared to be similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585046 TI - Synchronized excitation and inhibition driven by intrinsically bursting neurons in neocortex. AB - 1. The cellular mechanisms of synchronous synaptic activity were studied in isolated slices of rat SmI neocortex in which gamma-aminobutyric acid (GABA) mediated inhibition was slightly suppressed. Intracellular measurements were made from single neurons, and extracellular recordings monitored the timing and intensity of population events. 2. Neurons in cortical layers II-VI were classified by the attributes of their single action potentials and repetitive firing patterns during injection of intracellular current pulses. Regular-spiking (RS) cells occurred in all layers and had relatively long-duration spikes and strong frequency adaptation. Intrinsically bursting (IB) cells occurred only in layers IV and V and generated bursts of greater than or equal to 3 spikes; some IB cells of lower-layer V produced repetitive bursts during long depolarizing pulses. Fast-spiking (FS) cells had brief spikes and little or no adaptation and fired at high frequencies. 3. When GABAA-mediated inhibition was slightly reduced with low doses of bicuculline methiodide (BMI, 0.8-1.0 microM), synchronous events were evoked by stimulating layer VI with single shocks. Synchronous events were characterized by prominent, often all-or-none extracellular field potentials that propagated horizontally for variable distances up to several millimeters. Large field potentials were invariably correlated with excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in single neurons. Both PSPs and field potentials often had long (up to 250 ms) and variable latencies, and sometimes two or more events were generated by single stimuli. In all cases the PSPs and field potentials were synchronous. Both field potentials and single cells sometimes generated short epochs (3-7 peaks) of rhythmic events at 20-50 Hz. 4. The physiological class of single neurons was correlated with the relative dominance of excitation and inhibition during each synchronous event. In phase with each synchronous event, most RS cells were very strongly inhibited with only small amounts of concurrent excitation. By contrast, IB cells were strongly and consistently excited, with relatively little inhibition. FS cells were also phasically excited. 5. Anatomic studies have identified RS and IB cells as pyramidal cells and FS cells as GABAergic nonpyramidal cells. This implies that, during the synchronous events of the present study, the majority of pyramidal cells were dominated by IPSPs. Synchronous excitation of FS cells, the presumed inhibitory interneurons, is consistent with this. Only a subset of the pyramidal neurons, almost all of them IB cells of the middle layers, displayed strong, synchronous excitation and clusters of action potentials.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2585048 TI - Intra-axonal recordings of cutaneous primary afferents during fictive locomotion in the cat. AB - 1. Cutaneous primary afferents were recorded intracellularly during fictive locomotion in decorticated cats with the goal of improving our understanding of how locomotor networks might centrally control the transmission in cutaneous pathways at a presynaptic level. 2. Identified cutaneous axons from superficialis peroneal nerve (SP) or tibialis posterior nerve (TP) were recorded intracellularly together with the electroneurograms (ENGs) of representative flexor and extensor muscle nerves of the hindlimb as well as dorsal root potential from L6 or L7 (DRP). Fictive locomotion occurred spontaneously after decortication (n = 12) or was induced by stimulation of the mesencephalic locomotor region (MLR) (n = 6). 3. The results revealed that all cutaneous axons (82 units with resting potential greater than 45 mV) showed fluctuations of their membrane potential (greater than or equal to 0.5 mV) at the rhythm of the fictive locomotion. The characteristics of fluctuation patterns, common to all cutaneous units, consisted of two depolarization waves per cycle: one related to the flexor activity, the other related to the extensor activity. The flexor-related depolarization was followed by a sharp trough of membrane repolarization. The extensor-related depolarization usually overlapped partly with the flexor depolarization of the following cycle. The relative size of each depolarization could vary among different afferents of the same nerve in the same animal. Hence, maximal depolarization could occur in different parts of the locomotor cycle, but, for the majority of units (82%), it occurred during the flexor activity. These results were similar for SP and TP units. 4. Twenty percent of the units were discharging with a constant or irregular frequency. Phasic antidromic discharges related to locomotor ENGs were rarely encountered (5/82 units). 5. Linear regression analysis of the temporal relationships between fluctuations of membrane potential of cutaneous axons and locomotor bursts over several cycles showed that the timing of presynaptic events in cutaneous afferents is related to the events of the locomotor output. However, the same type of analysis showed that the amplitude of axonal depolarizations and the amplitude of flexor and extensor locomotor bursts could vary independently. Tight temporal relationships were also found between the depolarizations recorded in cutaneous units and the fluctuations recorded at the dorsal root level (DRP). 6. Based on the assumption that the locomotor fluctuations of cutaneous membrane potential are mediated through the primary afferent depolarization (PAD) pathways associated with presynaptic inhibition, it is proposed that the central pattern generator for locomotion (CPG) could phasically control the efficacy of transmission of cutaneous pathways at a presynaptic level as part of the locomotor program. PMID- 2585047 TI - Swimming in Aplysia brasiliana: behavioral and cellular effects of serotonin. AB - 1. Aplysia brasiliana is a marine mollusk that swims by repeated metachronal flapping movements of its bilateral fleshy parapodia. Animals with bilateral cerebropedal connective (CPC) lesions do not swim when suspended above the substrate, although tonic CPC stimulation can elicit normal parapodial flapping. Although the parapodial opener-phase (POP) cells, a previously identified group of neurons, fire synchronous bursts of efferent spikes in-phase with parapodial opening movements in both intact animals and dissected preparations, they are not likely to be primary parapodial motoneurons. These cells receive one or more large, apparently monosynaptic excitatory postsynaptic potentials (EPSPs) during CPC stimulation that are effective in producing the swimming motor program (SMP). 2. In suspended CPC-lesioned animals, injections of serotonin (5-HT) that produce an average hemolymph concentration of 10(-5) M induced full-amplitude parapodial flapping. Selected episodes of flapping were similar in frequency to normal suspended swimming. 3. In suspended CPC-lesioned animals, 5-HT injections elicited an apparently normal swimming motor program that was associated with synchronous bursts of large-amplitude efferent spikes in the parapodial nerves. In many semi-intact preparations, exposing the circumoesophageal ganglia to 5-HT elicited a similar rhythmic motor program, but usually at a lower frequency than during normal swimming or during tonic CPC stimulation. 4. In isolated-ganglion preparations, bath application of 5-HT produced immediate depolarization and tonic firing of individual POP neurons, followed by smooth and regular bursting in the apparent absence of synaptic input. In such preparations, the motor program elicited by bath-applied 5-HT differed from the one elicited by tonic CPC stimulation in that the 5-HT-elicited rhythmic bursting usually was not synchronous in different POP neurons. Tonic CPC stimulation during bath applications of 5-HT produced immediate synchronization of bursts among the POP neurons. 5. Hyperpolarization (or depolarization) of a POP neuron during bath application of 5-HT increased (or decreased) the burst period, but membrane polarization did not change the burst period elicited during tonic CPC stimulation. PMID- 2585050 TI - Mechanics of stretch in activated crustacean slow muscle. I. Factors affecting peak force. AB - 1. The active stiffness of ventral superficial abdominal muscle (VSM) of the hermit crab, Pagurus pollicarus, was measured with ramp stretches of different amplitudes and velocities. Active stiffness was calculated by subtracting the peak force produced by passive stretch and the isometric force just before stretch from the peak force produced by stretching active muscle. The result was then divided by stretch length to give stiffness. 2. The relationship between force just before stretch (the level of activation) and active stiffness was curvilinear and was found to apply under a variety of experiment conditions. For pooled data from eight experiments, active stiffness (GN.m-2.m-1) = 3.2*stress (MN/m2)-7.6*stress2. Decreasing the number of motor units or activating the inhibitor did not alter this relationship nor did the addition of proctolin, octopamine, or 5-HT to the bath. The relationship also applied during the rising phase of isometric tension. However, stiffness declined more rapidly than predicted by this relationship after the end of tetanus. 3. Active stiffness varied inversely with stretch amplitude for fast stretches, and the slope of this relationship increased with increasing muscle activation. At lower stretch velocities, the slope was much less than at rapid stretch velocities, so at low levels of activation and stretch velocity, active stiffness was essentially independent of stretch length. 4. Active stiffness covaried with muscle force as both were sampled at shorter and shorter lengths on the ascending limb of the length-tension curve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585049 TI - Role of competition among sensory neurons in regulation of pattern of innervation at their central and peripheral targets. AB - 1. The importance of competitive interactions among muscle sensory afferents on their projections to central and peripheral targets was studied by producing large reductions in the number of afferents during development. Removal of the brachial dorsal root ganglion (DRG2), which normally supplies the entire sensory innervation of the forelimb, in bullfrog (Rana catesbeiana) tadpoles caused a smaller number of neurons in the adjacent thoracic ganglion (DRG3) to sprout into the forelimb and into the brachial spinal cord. 2. Horseradish peroxidase labeling in postmetamorphic animals showed that DRG3 neurons innervating the triceps muscle arborize in a novel but now appropriate area of the spinal cord, the region containing motoneuronal dendrites. These foreign afferents do not arborize in inappropriate regions of the spinal gray matter, and their collaterals have the same rostrocaudal distribution as those of normal DRG2 muscle afferents. 3. After metamorphosis, the number of DRG3 sensory axons in individual triceps muscle nerves was determined. Normally, two-thirds of all triceps afferents project to the medial head alone, even though each of the three heads is of similar size and is contacted by similar numbers of motoneurons. After DRG2 removal, although the total number of DRG3 afferents projecting to the triceps muscle was smaller than normal, the medial head still received approximately two-thirds of the axons, just as in normal frogs. These results suggest that the proportional sensory innervation of the triceps muscle-heads is not dependent on competitive interactions among afferents. 4. DRG3 afferents projecting to the forelimb also sprouted to innervate appropriate brachial motoneurons. The average strength of connection between individual sensory and motor neurons was found to be the same as in normal animals, even though there was presumably more central target space available for each afferent axon. This suggests that the number and/or strength of central connections made by individual fibers may be an intrinsic property of muscle sensory neurons. PMID- 2585051 TI - Riluzole, a novel antiglutamate, prevents memory loss and hippocampal neuronal damage in ischemic gerbils. AB - The neuroprotective effects of riluzole, a novel antiglutamate, has been demonstrated in a model of ischemia induced in female Mongolian gerbils by transient bilateral carotid occlusion. Riluzole was administered at a dose of 4 mg/kg, i.p., just before, 4 hr after, and for the 14 d following the transient bilateral carotid occlusion (10 min). The functional sequelae of ischemic damage were assessed using a memory test (passive avoidance) and the extent of neuronal damage by histological examination and quantitative autoradiography of muscarinic cholinergic receptors in the hippocampus. The performance of the ischemic gerbils in the memory test was about half that of control animals. This memory deficit was completely reversed in animals treated with riluzole. This protective effect of riluzole was confirmed by histological and autoradiographic studies. The neuronal degeneration of CA1 pyramidal cells in the hippocampus observed in the ischemic group was not seen in the riluzole-treated animals, which resembled the control group. This neuronal degeneration in the CA1 area was confirmed by a quantitative measurement of muscarinic receptors: The binding was decreased by a third in the lacunosum moleculare, the stratum oriens, and the stratum radiatum. By contrast in riluzole-treated gerbils, this decrease was reversed by 50%. Finally, a clear-cut correlation was found between the deficit in the memory test and the decrease in muscarinic receptor binding in the CA1 fields. These results are compatible with the idea that glutamic acid may be involved in the neuronal degeneration of the hippocampus following ischemia, and could be foreseeable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585052 TI - Fibroblast growth factor and glutamate: opposing roles in the generation and degeneration of hippocampal neuroarchitecture. AB - Neuritic regression and cell death (neurodegeneration) are common features of both normal nervous system development and neurodegenerative disorders. Growth factors and excitatory amino acid neurotransmitters have been suggested independently to play roles in neurodegenerative processes. The present study investigated the combined effects of fibroblast growth factor (FGF) and glutamate on the development and degeneration of cultured hippocampal neurons. Consistent with previous data, we found that FGF, but not NGF, promoted neuronal survival and dendritic outgrowth. In contrast, a low level of glutamate (50 microM) caused a reduction in dendritic outgrowth, and high levels (100 microM-1 mM) reduced neuronal survival in a dose-dependent manner. When cultures were maintained in the presence of FGF, there was a striking reduction in neuronal death normally caused by 100-500 microM glutamate. FGF raised the threshold for glutamate neurotoxicity. FGF also antagonized the outgrowth-inhibiting actions of glutamate. Measurements of intracellular calcium levels with fura-2 demonstrated a direct relationship between glutamate-induced rises in intracellular calcium and neurodegeneration. FGF reduced the glutamate-induced increases in intracellular calcium levels. However, when cultures were pretreated with the RNA synthesis inhibitor actinomycin D or with the protein synthesis inhibitor cycloheximide, FGF did not prevent glutamate-induced increases in intracellular calcium or neurodegeneration. Taken together, these results suggest that (1) interactions between growth factors and neurotransmitters may be important in brain development; (2) imbalances in these systems may lead to neurodegeneration; and (3) cellular calcium-regulating systems may be a common focus of growth factor and neurotransmitter actions. PMID- 2585053 TI - Elementary processes of response selection mediated by distinct regions of the striatum. AB - The relative contributions of the medial and lateral caudate putamen to performance of a visual reaction time task were compared by examining the effects of unilateral ibotenate-induced lesions to these regions in the rat. Different groups of rats were trained to respond either towards (Discrimination 1) or away from (Discrimination 2) unpredictable, brief visual stimuli presented to either side of the head. Lateral striatal lesions produced a strong spatial bias towards the side of the lesion but left the latency for the initiation of responses to the visual cues unchanged. By contrast, the medial striatal lesions resulted in a smaller degree of spatial response bias but a significant slowing of initiation latency to the side contralateral to the lesion. These effects were irrespective of the side of the stimulus presentation and thus represent response-related impairments. The lesions were further dissociated in their effects on responding inappropriately to task requirements. These results demonstrate a double dissociation of behavioral effects of lateral and medial striatal damage that can be used to infer the operation of distinct elementary processes of response output within a single task. They are important not only in demonstrating functional effects of hypothetical segregated parallel corticostriatal loops but also in showing that these loops must interact to produce integrated performance. PMID- 2585054 TI - Axotomy-induced changes in the expression of a type III neuronal intermediate filament gene. AB - The effect of axotomy on the expression of the 57 kDa neuronal intermediate filament (IF) protein in adult rat dorsal root ganglion (DRG) neurons was examined. This IF protein is known to have an exclusively neuronal localization but is considerably more limited in its distribution in the nervous system than the neurofilament (NF) triplet proteins. The 57 kDa neuronal IF protein is similar (and perhaps identical) to the protein "peripherin" and is known to be the product of a Type III IF gene. Since the down-regulated expression of NF proteins (products of type IV IF genes) has been well established, it was of interest to determine whether the novel 57 kDa IF protein was regulated in a similar or different manner from that of the NFs in axotomized neurons. In vitro pulse-labeling of DRGs with 35S-methionine: cysteine followed by 2-dimensional gel electrophoresis/fluorography revealed that the synthesis of the 57 kDa neuronal IF protein was increased 2 weeks after sciatic nerve crush. Immunocytochemical studies using a polyclonal antibody to the 57 kDa neuronal IF protein showed that the immunodetectable levels of this protein increased in DRG neurons after peripheral axotomy. In the normal DRG, staining was localized almost exclusively to small-sized neurons. At 2 weeks after axotomy, however, large- and medium-sized neurons also became immunoreactive; in addition, the overall level of staining in the DRG was greater than normal. Quantitative analysis of in situ hybridizations of DRG neurons with a 35S-labeled cDNA probe specific for the 57 kDa neuronal IF protein revealed a significant increase in the level of 57 kDa IF mRNA in the large-sized (greater than 1000 microns2) neurons 2 weeks after axotomy; the level of 57 kDa IF mRNA in the small neurons was not different from normal at that time. Finally, using a newly developed paradigm for examining the composition of regenerating axons by axonal transport, we determined that significant amounts of the 57 kDa neuronal IF protein were conveyed into the regrowing axonal sprouts of DRG neurons. When DRG neurons were conditioned by a previous axotomy (a crush axotomy of the distal sciatic nerve 2 weeks earlier) and then stimulated to regenerate axons by a second crush axotomy located very close to the DRG, the regenerating sprouts incorporated and conveyed significantly more 57 kDa IF protein by slow axonal transport than did those elaborated by unprimed DRG neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2585056 TI - Quantified distribution of the noradrenaline innervation in the hippocampus of adult rat. AB - A recently developed radioautographic technique, based on the uptake labeling of monoamine terminals (axonal varicosities) in vitro, was used to quantify the noradrenaline (NA) innervation in adult rat hippocampus. After incubation of brain slices with 1 microM 3H-NA, the NA varicosities were visualized as small aggregates of silver grains, in light microscope radioautographs prepared at 3 equidistant horizontal levels across the ventral 2/3 of the hippocampus. Using a computer-assisted image analyzer, counts were obtained from the subiculum (SUB), 3 sectors of Ammon's horn (CA1, CA3-a, CA3-b) and 3 sectors of the dentate gyrus (DG-medial blade, crest, and lateral blade), every lamina being sampled in each region. After a double correction for duration of radioautographic exposure and section thickness, and following measurement of varicosity diameter in electron microscope radioautographs, it was possible to express these results in number of terminals per volumetric unit of tissue. It was thus found that the overall density of hippocampal NA innervation averages 2.1 million varicosities/mm3 of tissue, a value almost twice as high as that in cerebral cortex. This innervation is 20% denser ventrally than dorsally and is heterogeneous both in terms of regional and laminar distribution. SUB and DG are more strongly innervated than Ammon's horn, wherein CA1 has the lowest overall density. In SUB and CA1, there is a clear predilection of NA varicosities for the stratum moleculare. In CA3, there is a narrow band of even stronger innervation in the stratum radiatum, near the apical border of the stratum pyramidale, contrasting with a 3 times lower density in this cell layer and the stratum oriens. In DG, the NA innervation is again the weakest in the cell body layer (granule) and exhibits an almost 3-fold greater density in the polymorph layer, the highest of all hippocampus. These figures allow for numerous correlations with other quantitative parameters- cytological, biochemical, and pharmacological--of NA function in the hippocampus. They also provide a strong basis for elucidating, at a cellular level, the action of NA in this part of the brain. PMID- 2585055 TI - Inaccuracies in initial growth and arborization of chick retinotectal axons followed by course corrections and axon remodeling to develop topographic order. AB - The retinotectal projection is organized in a precise retinotopic manner. We find, though, that during development the growth and arborization of temporal retinal axons within the optic tectum of chick embryos is initially imprecise. Axonal targeting errors occur along the rostral-caudal and medial-lateral tectal axes, and arbors are formed at topographically inappropriate positions. Subsequent course corrections along both tectal axes and large-scale axonal remodeling lead to the retinotopic ordering of terminal arborizations characteristic of the mature projection. The trajectories and branching patterns of temporal retinal axons labeled with Dil or DiO were determined in whole mounts of retina and tectum from chicks ranging in age from embryonic day 9 to posthatching. Within the retina, labeled retinofugal axons travel in a compact bundle but do not maintain strict neighbor relations, as they course to the optic fissure. The axons enter the contralateral tectum at its rostral edge and grow caudally. Many extend well past their appropriate terminal zone within rostral tectum; a proportion of these later reverse their direction of growth. Many axons grow onto the tectum at incorrect positions along the medial-lateral tectal axis. Some correct this error in a directed manner by altering their trajectory or extending collateral branches at right angles. About 80% of the positional changes of this type are made in the direction appropriate to correct axon position, and thus are likely a response to tectal positional cues. After maturation of retinotopic order, about half of the axons that project to a mature terminal zone have made abrupt course corrections along one or both tectal axes, indicating that initially mistargeted axons can establish appropriately positioned arbors and survive. The development of temporal axons within the tectum is characterized by 3 phases: elongation, branch and arbor formation, and remodeling. After considerable rostrocaudal elongation, an axon typically develops numerous side branches and arbors, many at inappropriate locations. Most arbors are formed by side branches that develop as interstitial collaterals; few axons grow directly to their appropriate terminal zone and arborize. Aberrant arbors, and axons and axon segments that fail to form arbors in the appropriate terminal zone, are rapidly eliminated over about a 2 d period. Axon degeneration appears to play a role in this remodeling process. PMID- 2585057 TI - Neural circuits mediating visual flight control in flies. I. Quantitative comparison of neural and behavioral response characteristics. AB - The motion-sensitive horizontal cells in the lobula plate of the fly are assumed to play a key role in the sensory control of yaw torque generated by the flying animal during course-stabilization maneuvers and the fixation of objects. This inference results from comparisons of electrophysiological data obtained from blowflies (Calliphora erythrocephala) and behavioral data obtained mainly from houseflies (Musca domestica) and fruitflies (Drosophila melanogaster). Apart from few exceptions, the compatibility of these physiological and behavioral data has not been critically tested. In the present study, the responses of the equatorial horizontal cell HSE of Calliphora and the yaw torque responses of Calliphora and Musca were recorded under identical visual stimulation with moving periodic gratings. The goal of the experiments was to obtain electrophysiological and behavioral data on Calliphora, on the one hand, and behavioral data on Calliphora and Musca, on the other hand, that allow direct comparisons between the physiological properties of the HSE and the visually induced torque responses in both species. The dependence of the HSE responses and the yaw torque responses on the direction, contrast frequency, and brightness of a moving periodic grating were evaluated quantitatively. The results of the electrophysiological recordings and torque measurements are in close agreement and thus represent strong evidence that the horizontal cells are, in fact, involved in yaw torque control in both species. Measurements of the cellular and behavioral responses as function of the stimulus position in the visual field, however, reveal differences between the spatial sensitivity of the horizontal cells and the sensory input to the motor system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585058 TI - Penetrating head injury in young adulthood exacerbates cognitive decline in later years. AB - Few investigators have studied whether the behavioral effects of brain insult in adulthood are stable after the period of maximum recovery. We addressed this issue in a 30-year longitudinal study of 84 veterans of World War II, 57 with penetrating head injury (HI) and 27 with peripheral nerve injury (PNI), matched with respect to age, premorbid intelligence, and premorbid education. Each subject was examined during the 1950s and during the 1980s; each examination included the largely verbal Army General Classification Test (AGCT) (with Vocabulary, Arithmetic, and Block Counting subscales) and the Hidden Figures Test (which measures figure-ground discrimination). HI exacerbated decline in performance over time, irrespective of lesion site or cognitive test. HI and PNI subjects differed significantly (p less than 0.05) in AGCT Total and Arithmetic change scores, and means were in the same direction for all other measures. In analyses contrasting subjects in each of the eight lesion groups to PNI subjects, those with left parietal lobe injuries showed significantly greater decline from the 1950s to the 1980s on the Vocabulary and Arithmetic subscales of the AGCT, as did those with left temporal lobe injuries on the Arithmetic subscale, whereas subjects with right parietal lobe injuries showed significantly greater decline on the Hidden Figures Test. We hypothesize that the observed reduction of cognitive capacities late in life was due to some combination of HI in young adulthood, secondary effects of the injury occurring with time, effects of stress on remaining brain tissue caused by functioning for decades in a compromised state, and changes in the brain occurring with age. Although the HI subjects were not demented, follow-up studies must assess whether exacerbated decline is a harbinger of dementia. PMID- 2585059 TI - Administration of testosterone attenuates neuronal loss following axotomy in the brain-stem motor nuclei of female rats. AB - This study was undertaken to elucidate whether (1) administration of testosterone to female rats attenuates axotomy-induced neuronal loss; (2) the efficacy of testosterone treatment is related to the age of animals, the dosage given, and the time and duration of the treatment; (3) neurons which project or terminate aberrantly can survive; and (4) the trophic actions of testosterone on neuronal survival and axonal outgrowth are operated under the same mechanisms. The hypoglossal and facial nerves were transected unilaterally at 3 and 6 weeks of age. In order to establish the dose-response curve, testosterone propionate (TP) at doses of 0.5, 1.0, 2.0, or 5.0 mg was injected subcutaneously twice weekly during the first 4 postaxotomy weeks, and once weekly thereafter for an additional 6 weeks. Neuronal numbers in the hypoglossal and facial motor nuclei were counted 10-12 weeks after axotomy in serial paraffin sections stained with cresyl violet. To determine the time course of TP effect, neuronal numbers were counted at 1, 4, 12, and 20 weeks after axotomy. In addition, neuronal loss 12 weeks after axotomy in rats treated with TP for the first 3 postaxotomy weeks only was compared with that in rats withheld TP treatment until the 5th postaxotomy week. To determine axonal projections and terminations of the surviving neurons, HRP retrograde tracing technique was used. Results indicated that TP treatment significantly attenuated neuronal loss in prepubertal and young adult female rats in a dose- and time-dependent manner. Only doses which elevated serum testosterone to levels comparable to or surpassing normal male levels were effective.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585060 TI - Preserved spatial coding in hippocampal CA1 pyramidal cells during reversible suppression of CA3c output: evidence for pattern completion in hippocampus. AB - Medial septal modulation of hippocampal single-unit activity was examined by assessing the behavioral and physiological consequences of reversibly inactivating the medial septum via microinjection of a local anesthetic (tetracaine) in freely behaving rats trained to solve a working memory problem on a radial maze. Reversible septal inactivation resulted in a dramatic, but temporary (15-20 min), impairment in choice accuracy. In addition, movement induced theta (theta) modulation of the hippocampal EEG was eliminated. Septal injection of tetracaine also produced a significant reduction in location specific firing by hilar/CA3c complex-spike cells (about 50%), with no significant change in the place-specific firing properties of CA1 complex-spike units. The mean spontaneous rates of stratum granulosum and CA1 theta cells were temporarily reduced by about 50% following septal injection of tetracaine. Although there was a significant reduction in the activities of inhibitory interneurons (theta cells) in CA1, there was no loss of spatial selectivity in the CA1 pyramidal cell discharge patterns. We interpret these results as support for the proposal originally put forth by Marr (1969, 1971) that hippocampal circuits perform pattern completion on fragmentary input information as a result of a normalization operation carried out by inhibitory interneurons. A second major finding in this study was that location specific firing of CA1 cells can be maintained in the virtual absence of the hippocampal theta-rhythm. PMID- 2585061 TI - Development of inhibitory synapses among striatal neurons in vitro. AB - The development of excitatory and inhibitory synaptic connections has been studied in postnatal neurons from the caudate and putamen maintained in tissue culture. Excitatory postsynaptic potentials which were sensitive to the glutamate antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) appeared between 4 and 8 d in vitro. This is the first indication that glutamatergic excitatory neurons may be intrinsic to the striatum. Spontaneous inhibitory postsynaptic currents appeared at approximately the same time, several days after process outgrowth. Antibodies to glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA, labeled neurons which produce bicuculline-sensitive, inhibitory postsynaptic currents. GAD immunoreactivity and immunoreactivity to synapsin I, a synaptic vesicle-associated protein, became localized to discrete sites along neurites 4-8 d after plating. It is concluded that the punctate GAD immunoreactivity identified possible sites of presynaptic transmitter release. PMID- 2585062 TI - Postischemic synaptic physiology in area CA1 of the gerbil hippocampus studied in vitro. AB - After transient forebrain ischemia in the Mongolian gerbil, CA1b hippocampal pyramidal cells degenerate during a period of 2-4 d. We tested the hypothesis that this delayed neuronal death is preceded by excessive synaptic excitation. Hippocampal slices were prepared from gerbils that had been subjected to a 5 min occlusion of both common carotid arteries. Input/output curves demonstrated enhancement of the initial slope of the Schaffer collateral-commissural focally recorded EPSP at all stimulus currents between 5 and 10 hr after the ischemic insult. The duration of the focally recorded EPSP also increased. At the same time, the excitability of the CA1b pyramidal cells decreased. Thus, the EPSP brought fewer pyramidal cells to threshold than the same size EPSP in control slices. During the first 14 hr after ischemia, the antidromic population spike remained unaffected. By 24 hr after ischemia, however, the focally recorded EPSP and both orthodromic and antidromic population spikes were markedly depressed, and they declined further over the next 2 d. No recovery was detected. In the same slices, transient ischemia only mildly and reversibly affected the response of dentate granule cells to perforant path stimulation and did not affect their response to antidromic stimulation. Hippocampal slices adjacent to those used for electrophysiological recording were analyzed histologically. Examination of somatic argyrophilia confirmed that CA1b pyramidal cells suffered delayed neuronal death, whereas dentate granule cells remained intact. Pyramidal cell argyrophilia was, however, not detected until 2 d after these neurons had become virtually inexcitable. We conclude that CA1b pyramidal cells begin to lose electrophysiological function well before definite morphological signs of degeneration become visible. The observation of enhanced excitatory transmission 5-10 hr after reperfusion is consistent with the idea that delayed ischemic neuronal death results, at least in part, from excessive excitation. PMID- 2585064 TI - Elevated cytosolic calcium in the growth cone inhibits neurite elongation in neuroblastoma cells: correlation of behavioral states with cytosolic calcium concentration. AB - Schubert (1984) and Kater et al. (1988) have suggested that motility and growth at the neuronal growth cone is activated by an increase of cytosolic free calcium concentration ([Ca2+]i) above the levels found in quiescent growth cones. In order to test this model, we have used a digital imaging fluorescence microscope together with injection of the fluorescent indicator dye Fura-2 to measure [Ca2+]i in growth cones of a mammalian sympathetic neuron, the N1E-115 neuroblastoma cell. The behavior of individual growth cones, together with spontaneously varying levels of [Ca2+]i within the growth cone, were monitored for periods of up to several hours. [Ca2+]i in motile, advancing growth cones was low and equal to [Ca2+]i in quiescent growth cones. Higher values of [Ca2+]i were found in motile growth cones that were not advancing, suggesting that a small elevation of [Ca2+]i inhibits neurite extension. A further rise of [Ca2+]i above the level found in motile, nonadvancing growth cones appeared to inhibit motility and cause retraction of the growth cone back towards the cell body. Spatial gradients of [Ca2+]i within the growth cone were small and, where statistically significant, [Ca2+]i was lower by 5-10 nM in motile regions. Our results are incompatible with the model that a rise of [Ca2+]i is responsible for activating quiescent growth cones; however, our results suggest that in active growth cones [Ca2+]i can regulate morphology and behavior. PMID- 2585065 TI - Diversity of the transient outward potassium current in somata of identified molluscan neurons. AB - We have undertaken a quantitative study of the differences in the properties of the fast transient outward current (A-current) between identified neurons of 2 species of nudibranch mollusc. Somata from identifiable neurons of Archidoris montereyensis and Anisodoris nobilis were isolated and voltage-clamped with a 2 microelectrode voltage clamp at 11 degrees C. We examined diversity in the expression of the time- and voltage-dependent properties of A-current by measuring the following parameters: (1) current magnitude, (2) current density, (3) inactivation kinetics, (4) the voltage dependence of steady-state activation and inactivation. We first characterized A-current in each cell type by measuring these parameters for each identified neuron in a series of animals of a given species. The results of these measurements were used to describe the A-current properties of an identified neuron in terms of a mean and SD. The SD measured diversity within the animal population for any given cell type, while the mean values could be compared to measure diversity in the expression of A-current between identified neurons. When we compared mean values for A-current properties between identified neurons of a given species, we did not detect statistically significant differences in the steady-state voltage dependence of activation and inactivation. However, there were statistically significant differences in peak A current magnitude, density, and inactivation kinetics between identified neurons. We examined differences between the species by comparing the A-current properties of homologous neurons. The major difference between the species was that outward current magnitude and density were significantly greater in Anisodoris than in Archidoris. We conclude that the magnitude and density of A-current differ between identified nudibranch neurons. The neurons also differentially express A current inactivation kinetics in a cell-specific manner. PMID- 2585066 TI - Regional cerebral glucose utilization reveals widespread abnormalities in the motor system of the rat mutant dystonic. AB - Rats with an inherited movement disorder (dystonic, dt), their phenotypically normal littermates, and normal unrelated controls were studied using a metabolic mapping technique, 2-deoxyglucose autoradiography. This approach was used to identify potential sites of abnormality underlying the movement disorder, as no morphological abnormalities using light and electron microscopic techniques have been identified in this mutation. There was a significant overall glucose utilization (GU) reduction in the dt rats and their littermate controls when they were at rest and not displaying abnormal movements. Conversion of GU values to standard scores showed abnormalities in dt compared with both control groups in the following areas: deep cerebellar nuclei, locus coeruleus, pontine gray, ventrolateral-ventromedial thalamic complex, nucleus of the third nerve, lateral habenula, and basolateral amygdala. Littermates were different from nonlittermates in several regions, including the dentate and red nuclei. A study of relative GU performed in animals displaying dystonic movements also showed abnormalities in the deep cerebellar nuclei and locus coeruleus, and in the red nucleus, external cuneate, and medial septum. Correlations computed for GU in pairs of regions with known anatomical connections suggested that cerebellar, substantia nigra, and basal ganglia efferents may be abnormal. These studies complement existing biochemical and neuropharmacological data which show abnormalities in the cerebellum of the dt rat. Additionally, the function of brain stem and even basal ganglia nuclei is affected in this mutant, perhaps as a consequence of abnormal cerebellar activity. The partial effects in the littermates suggest that abnormalities in only a few regions are not sufficient to produce the movement disorder, and a gene dose effect may exist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585063 TI - Norepinephrine and learning-induced plasticity in infant rat olfactory system. AB - Postnatal olfactory learning produces both a conditioned behavioral response and a modified olfactory bulb neural response to the learned odor. The present report describes the role of norepinephrine (NE) on both of these learned responses in neonatal rat pups. Pups received olfactory classical conditioning training from postnatal days (PN) 1-18. Training consisted of 18 trials with an intertrial interval of 24 hr. For the experimental group, a trial consisted of a pairing of unconditioned stimulus (UCS, stroking/tactile stimulation) and the conditioned stimulus (CS, odor). Control groups received either only the CS (Odor only) or only the UCS (Stroke only). Within each training condition, pups were injected with either the NE beta-receptor agonist isoproterenol (1, 20, or 4 mg/kg), the NE beta-receptor antagonist propranolol (10, 20, 40 mg/kg), or saline 30 min prior to training. On day 20, pups received one of the following tests: (1) behavioral conditioned responding, (2) injection with 14C-2-deoxyglucose (2-DG) and exposed to the CS odor, or (3) tested for olfactory bulb mitral/tufted cell single-unit responses to the CS odor. The results indicated that training with either: (1) Odor-Stroke-Saline, (2) Odor-Stroke-Isoproterenol-Propranolol, or (3) Odor only-Isoproterenol (2 mg/kg) was sufficient to produce a learned behavioral odor preference, enhanced uptake of 14C-2-DG in the odor-specific foci within the bulb, and a modified output signal from the bulb as measured by single-cell recordings of mitral/tufted cells. Moreover, propranolol injected prior to Odor Stroke training blocked the acquisition of both the learned behavior and olfactory bulb responses. Thus, NE is sufficient and may be necessary for the acquisition of both learned olfactory behavior and olfactory bulb responses. PMID- 2585067 TI - Innervation of the kidney of Aplysia by L10, the LUQ cells, and an identified peripheral motoneuron. AB - The purpose of this study was to begin to describe the neural circuit within the abdominal ganglion that modulates renal functioning in Aplysia. We found that the previously described cholinergic neuron L10 and peptidergic left upper quadrant (LUQ) neurons have important roles in the control of the kidney. Cell L10 and a subset of the LUQ cells branch extensively within the kidney and send major processes to the renal pore, a sphincter that controls the efflux of urine. The renal pore has circular (closer) and radial (opener) muscle fibers that act as antagonists. Embedded within the wall of the renal pore is a newly identified peripheral neuron, RPO, which is a renal pore opener motoneuron. L10 activity causes opening of the renal pore by directly exciting pore opener muscle, inhibiting closer muscle, and exciting RPO. When RPO is active, it generates synchronous, discrete twitches in the opener muscle fibers. The action potentials recorded in RPO exhibit pronounced broadening at physiological rates of firing. LUQ cells that project to the renal pore cause it to close, and they antagonize the opening generated by an L10 burst. The pore closing caused by the LUQ cells is mediated in part by heterosynaptic inhibition of the L10 to RPO excitatory connection. The previously described central inhibitory connections from L10 to the LUQ cells ensure that these 2 classes of antagonists fire out of phase with each other. Our data, along with those from earlier studies demonstrating that L10 plays an important role in controlling the circulatory system, suggest that L10 and the LUQ cells modulate various aspects of renal function in Aplysia, including filtration and micturition. PMID- 2585068 TI - Clustered distribution and variability in kinetics of transient K channels in molluscan neuron cell bodies. AB - The spatial distribution of transient K current, IA, was studied using a combination of patch-clamp and whole-cell voltage-clamp techniques. The average IA current density in somatic patches is 0.64 times the current density in the entire axotomized cell body, a finding which suggests that the axon hillock or initial segment of the axon has a higher concentration of IA channels than much of soma. The highest density of active channels during the peak IA is 1/micron2 at a membrane voltage of -20 mV. There is no evidence for a gradient in the distribution of IA channels in the cell body, but the channels are not evenly distributed. The variability in the number of channels per patch for multiple patches on the same neuron is much higher than expected for a random distribution. Statistical analysis of the data yields a coefficient of dispersion of 8.1, a value indicating a high degree of clustering. The utility of this statistic for evaluating channel distributions is discussed. Several lines of evidence suggest that the upper limit for the area of IA channel clusters is approximately 250 micron2. Single-channel currents attributed to IA were recorded in the cell-attached configuration. The voltage dependence of channel opening and inactivation are the same as measured in whole-cell voltage-clamp experiments. The single-channel conductance is about 9 pS in normal saline. Patches 9-30 micron2 in areas that contain IA channels are often devoid of other K channel types, suggesting that IA channels can occur in isochannel clusters. IA inactivation follows an exponential time course in all of the neurons examined, but the time constant of inactivation ranges from 25 to 560 msec in different cells. The voltage dependence of activation and inactivation and the reversal potential of the current are approximately the same in all cells. When multiple patches on the same neuron are studied, it is found that IA inactivates exponentially with approximately the same time constant in each patch, regardless of patch area. The data suggest that each neuron expresses predominantly, and perhaps exclusively, a single type of IA channel with distinct kinetic properties. The wide range of IA inactivation time constants observed in different cell suggests that a large number of channel types are available for expression. Possible mechanisms for generating diversity in channel types are discussed. PMID- 2585069 TI - Natural course of unoperated intracranial arteriovenous malformations: study of 50 cases. AB - The clinical course of 50 patients with conservatively treated intracranial arteriovenous malformations (AVM's) was followed, most of them for more than 5 years. The average follow-up period was 13.4 years. The initial symptom was intracranial bleeding in 29 patients (58%) and seizure in 15 patients (30%). Small and deep-seated AVM's were associated with a high incidence of bleeding; however, repeated hemorrhages were not necessarily indicative of a poor prognosis. Children younger than 15 years had a better prognosis than adults. There was no correlation between pregnancy and bleeding. In the hemorrhage group, the incidence of rebleeding was 6.9% in the 1st year after initial rupture, 1.91% per year after 5 years, and 0.92% per year after 15 years. The overall incidence of rebleeding was 34.5% in the hemorrhage group. Of the 50 patients, 37 (74%) had a good clinical outcome, four (8%) had a fair outcome, and four (8%) had a poor outcome; five patients died. PMID- 2585070 TI - Surgery of spinal nerve schwannoma. Risk of neurological deficit after resection of involved root. AB - When surgically removing a spinal nerve schwannoma, preservation of the involved root is attempted and may be feasible. However, in large tumors, sacrifice of the nerve root is often required to achieve total removal of the tumor, and the resection does not always result in postoperative neurological deficit. The present study was designed to determine the incidence and extent of neurological deficit as correlated with resection of the root, performed between 1976 and 1987 in 86 cases at the time of total removal of spinal schwannoma. Thirty-one patients underwent sacrifice of a root critical for the function of the upper (C5 T1, 14 cases) or the lower extremities (L3-S1, 17 cases). This report is limited to these 31 cases. Only seven patients (23%) developed detachable motor or sensory deficits postoperatively. All deficits were no more than partial loss of strength or sensation. Fifteen of the 31 patients had large tumors with extradural components, which necessitated sacrifice of the entire motor and sensory radix; however, 11 (76%) of these 15 did not develop any deficits referrable to the involved myotome or dermatome. Six cases showed histological characteristics of "neurofibroma," with axons intermingled in the tumor, and none developed a postoperative deficit. Preoperative electromyography was performed in 23 cases. Of 13 patients with findings of denervation, five developed deficits after surgery; the other 10 patients showed no evidence of denervation, and none had deficits after surgery. These results indicate that the spinal roots giving origin to schwannoma are frequently nonfunctional at the time of surgery, and risks of causing disabling neurological deficit after sacrificing these roots are small. PMID- 2585071 TI - Results of reoperation for failed epilepsy surgery. AB - A total of 37 patients who failed epilepsy surgery were evaluated with magnetic resonance imaging and long-term scalp electroencephalographic monitoring before reoperation. Repeat surgery involved focal resections after initial focal resections (30 cases) or stereotactic lesions (one case), or focal resections following anterior corpus callosotomy (six cases). Patients with initial focal resections followed by enlargement of the original operative site had the most successful outcome, especially those with complex partial seizures of temporal lobe origin. The most common cause for poor outcome of the original operation in patients with temporal lobe epilepsy was insufficient hippocampal resection. Patients who were most likely to benefit from reoperation were: 1) those with initially incompletely resected structural lesions; 2) those who were initially evaluated with invasive ictal monitoring; and 3) those who underwent further resection of the initial operative site rather than resection of a different cortical region. PMID- 2585074 TI - The lateral extracavitary approach to the spine using the three-quarter prone position. AB - A three-quarter prone position for the lateral extracavitary operative approach to the thoracic and lumbar spine is described. This approach has been used in 40 patients with anterior spinal cord compressive lesions in the thoracic and/or lumbar region. In this patient population, it has allowed a safe ventral decompression of the spinal cord. It also allows placement of spinal instrumentation through the same incision. Both the operating surgeon and the assistant have an excellent view of the operative site, including the dural sac. Patient positioning and the operative approach are described and illustrated. PMID- 2585072 TI - Pre-irradiation chemotherapy for infants and children with medulloblastoma: a preliminary report. AB - From March, 1984, through June, 1987, 21 newly diagnosed children with high-risk medulloblastoma (Chang Stage T3 to T4) were treated on a 9-week postoperative, pre-irradiation chemotherapy regimen consisting of vincristine and cisplatin. The children over 2 years old then received radiation therapy. Six infants (aged 6 to 18 months) were maintained on chemotherapy consisting of MOP (nitrogen mustard, vincristine, and procarbazine) until the age of 2 years, at which time they were referred for irradiation. Of 13 children with measurable disease following surgery, five showed a definite response on computerized tomography scans to vincristine and cisplatin (one complete response and four partial responses) and five others showed clear marginal responses. Four of the six infants were disease free at 19, 32, 35, and 57 months from diagnosis. One infant developed progressive disease at the completion of the vincristine and cisplatin course, and a second infant had progression during MOP administration. Three of the 21 children developed hearing loss within the speech frequencies during cisplatin treatments, but there were no other major toxicities. Fifteen children remained disease-free with a median follow-up period of 35 months (range 19 to 57 months). Chemotherapy given between surgery and radiotherapy may allow for the direct evaluation of a specific drug regimen and permit the postponement of radiation therapy in infants. Pre-irradiation vincristine and cisplatin was well tolerated and effective in shrinking the tumor in most children with medulloblastoma. Such chemotherapy regimens have the potential for extending long-term survival in high risk children. PMID- 2585073 TI - National survey of patterns of care for brain-tumor patients. AB - An excellent response by participating institutions was realized in this survey of patterns of care for patients with primary brain tumors. Since the histopathology of the tumor is such a strong predictor of outcome and influences care so greatly, most analyses were performed not only on the overall series of patients but also by World Health Organization histological classification. Several factors that influence outcome were identified: tumor type, patient age, patient Karnofsky rating, tumor location, and therapy. Very few cases were coded as regards the American Joint Committee on Cancer clinical stage, and few potentially eligible cases were placed in investigative protocols. It behooves those centers providing investigative protocol opportunities to develop liaisons with practicing physicians nearby as well as at some distance and to provide an organizational framework that will make participation in these protocols practical for a larger segment of our brain-tumor patient population. Between 1980 and 1985, the increased use of magnetic resonance imaging in neuroradiology is apparent as well as the increased use of stereotactic biopsy and interstitial radiotherapy. Complications of therapy seem acceptably low. Five-year survival for benign brain tumor is high, while that for the most common primary tumor, glioblastoma multiforme, is only 5.5%. Some of the findings in this survey confirm those from the literature while others, particularly the pattern of care, represent new data. PMID- 2585075 TI - Primary intraspinal neoplasms in Norway, 1955 to 1986. A population-based survey of 467 patients. AB - A survey of all patients (173 males and 294 females) registered with primary intraspinal neoplasms in the Norwegian Cancer Registry from 1955 through 1986 is presented. Annual age-adjusted incidence rates of new tumors per one million population were three for males and five for females. Altogether, 89% of the tumors were verified histologically. Meningioma was the most common tumor type, followed by ependymoma and neurilemoma. Intraspinal ependymomas accounted for 34.5% of all 223 ependymomas of the central nervous system, whereas only 0.2% of the 3046 glioblastomas were found intraspinally. Patients with intraspinal meningioma had a better life expectancy than those with intracranial meningioma. The 5-year relative survival rate for patients with intraspinal ependymoma was 88.9% in contrast to 24.4% for patients with intracranial ependymoma. PMID- 2585076 TI - Surgical alternatives in the treatment of cavernous sinus aneurysms. AB - Direct surgery on aneurysms in the cavernous sinus is a formidable technical procedure. The intimate relationship of the intracavernous carotid artery to the venous structures and to the cranial nerves make surgical access difficult at best. Thirty-two of 356 aneurysm patients presented with symptomatic aneurysms originating from the intracavernous internal carotid artery. Twenty-one patients had aneurysms contained entirely within the cavernous sinus, and in 11 others the aneurysms arose within the cavernous sinus and extended into the subarachnoid space. Of the purely intracavernous aneurysms there were five small aneurysms (less than 25 mm) and 16 giant (greater than or equal to 25 mm) aneurysms. Fifteen patients with purely intracavernous lesions had a superior orbital fissure syndrome, and six had a variety of other symptoms. Of 11 patients with subarachnoid extension, five had a subarachnoid hemorrhage (Grade I or II), five had ipsilateral visual loss, and one had periorbital pain. The aneurysms were treated as follows: Group 1 received progressive ligation of the internal carotid artery in the neck with a Selverstone clamp and a surface superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis (purely intracavernous in nine, and with subarachnoid extension in one); Group 2 underwent trapping of the internal carotid artery and a deep STA-MCA anastomosis (purely intracavernous in seven); and Group 3 had direct clipping of the aneurysm (purely intracavernous in five, and with subarachnoid extension in 10). The cavernous sinus was entered directly through its roof by a pterional craniotomy with radical removal of the optic canal, lesser sphenoid wing, and lateral and superior orbital walls. Proximal control of the internal carotid artery was obtained through a cervical incision. Two patients in Group 1 developed transient neurological deficits, which resolved. Two patients in Group 2 developed a cerebral infarction, one of whom died; in both of these patients, the anastomosis was completed after the internal carotid artery occlusion. Two patients in Group 3 progressed from marked visual loss to blindness of the same side, and one developed an intraventricular hemorrhage during induction of anesthesia and died without surgery. It is proposed that a direct approach to symptomatic aneurysms in the cavernous sinus is the best initial alternative. When this approach is not feasible, a trapping procedure preceded by a high-flow extracranial-intracranial anastomosis may be considered. Although the authors have been able to clip aneurysms of various sizes, this has not been possible in all patients. Further work is needed in this area. PMID- 2585077 TI - Traumatic carotid artery dissection: diagnosis and treatment. AB - Early diagnosis and successful management of traumatic carotid artery dissections require a high index of clinical suspicion. The diagnostic study of choice is cerebral arteriography. In this paper, 24 cases of traumatic carotid artery dissection are described. Presenting signs and symptoms include Horner's syndrome, dysphasia, hemiparesis, obtundation, and monoparesis. Patients detected early with mild neurological deficits fared well with treatment, while those with profound neurological deficits and delayed diagnoses had poor outcomes. Aggressive nonsurgical treatment is advocated including anticoagulation therapy for prevention of progressive thrombosis and arterial occlusion and/or distal arterial embolization with resultant cerebral ischemia. Direct surgical thromboendarterectomy is considered to carry high morbidity and mortality rates. PMID- 2585078 TI - Acute subdural hematomas: an age-dependent clinical entity. AB - Reports prior to 1980 describe overall mortality rates for acute subdural hematomas (SDH's) ranging from 40% to 90% with poor outcomes observed in all age groups. Recently, improved results have been reported with rapid diagnosis and surgical treatment. A relatively large number of older patients (34 patients over 65 years old) were treated recently at Harborview Medical Center, enabling a retrospective comparison with similarly treated younger patients (33 patients aged 18 to 40 years). Clinical information and computerized tomography morphometric data were obtained. Patients in the younger group were most often injured in motor-vehicle accidents (15 cases), whereas falls were most frequent in the older group (19 cases). Patients in both groups were rapidly resuscitated in the field; more than 30% were treated within 1 hour after the time of injury. Injury severity, determined by the admission Glasgow Coma Scale score, was similar for the two groups. Mean acute SDH volume was significantly larger in the older patients than in the younger group (mean +/- standard deviation: 96.2 +/- 117.2 vs. 21.6 + 27.7 cu cm), as was the amount of midline shift (1.2 +/- 1.69 vs. 0.6 +/- 0.75 cm). Surgical treatments were similar, but outcomes were dramatically different for the younger and older patients. Mortality rates were more than four times higher in older patients than in younger ones (74% vs. 18%). Three older patients and 25 younger patients were functional survivors. Old age, a larger SDH volume, and a larger midline shift all correlated with a poor outcome. The results of this study suggest that the pathophysiology of acute SDH varies with age, and that currently employed resuscitation and treatment methods have differentially improved the outcome for younger patients. PMID- 2585079 TI - Cerebral blood flow and glucose metabolism in experimental brain edema. AB - The relationship between cerebral blood flow (CBF) and cerebral metabolic rate of glucose (CMRgl) in the white matter was studied in a plasma infusion model of vasogenic edema in cats. Local CBF, as determined by iodoantipyrine testing, was found to be significantly decreased in edematous white matter (mean +/- standard error of the mean: 17.3 +/- 1.5 ml/100 gm/min) when compared with CBF in the contralateral control white matter (24.8 +/- 1.8 ml/100 gm/min). When the values for edematous brain were corrected for dilution, however, the local CBF averaged 25.3 +/- 1.7 ml/100 gm/min, which was similar to the control value. Local CMRgl was found to be significantly increased in plasma-infused white matter (16.3 +/- 2.2 mumol/100 gm/min) compared with that in control white matter (10.7 +/- 1.3 mumol/100 gm/min). This difference remained, despite correction for dilution and recalculation of local CMRgl values based on altered kinetic constants found in edematous brain. A similar increase in local CMRgl was noted with saline-infusion edema. It is concluded that the increased tissue water level does not alter CBF, but does induce an increase in anaerobic metabolism. PMID- 2585080 TI - Isolation and partial purification of growth factors with TGF-like activity from human malignant gliomas. AB - The effect of concentrated conditioned medium from each of eight human malignant glioma cell lines on the growth of indicator cells (normal rat kidney fibroblasts (NRK), clone 14) was determined in monolayer and in soft agar assay systems. The conditioned medium from all cell lines was mitogenic in the monolayer assay, but only SF-210, U-343 MG-A, and U-251 MG produced soluble factors that caused NRK cells to grow in soft agar. The soluble growth-promoting factors from these three cell lines were acid- and heat-stable (60 degrees C for 30 minutes) but were inactivated by trypsin (100 microns/ml) and dithiothreitol (50 microM). The growth factors from SF-210 and U-343 MG-A were further purified by molecular sieve chromatography. The partially purified growth factor from U-343 MG-A retained transforming growth factor (TGF)-like activity, had a molecular weight of 9 kD, was potentiated by TGF-beta in the soft agar assay, competed effectively with 125I-epidermal growth factor (EGF) radiolabeled for the EGF receptor on A 431 epidermoid carcinoma cells, and was completely inhibited by monoclonal antibodies to TGF-alpha. The partially purified growth factor from SF-210 had a molecular weight of 17 kD, was not inhibited by monoclonal antibodies to platelet derived growth factor (PDGF) or TGF-alpha, and did not bind to a heparin Sepharose column. These results imply that U-343 MG-A secretes a growth factor with TGF-alpha-like activity, and SF-210 secretes a TGF with neither TGF-alpha nor TGF-beta activity. PMID- 2585082 TI - Monoclonal antibodies with cytotoxic reactivities against human gliomas. AB - Monoclonal antibodies (MAb's) reactive with human malignant glioma cells were derived from mice inoculated with cells from fresh glioma tissue. Seven MAb's were selected for study based on their high-level binding in immunoperoxidase and immunofluorescence assay to most of the glioma tissues derived from various patients and based on the absence of binding to normal bone marrow cells. Four of the seven MAb's did not bind to any of the four normal brain tissues tested, whereas three MAb's bound to one or two of these tissues. Two MAb's bound to the surfaces of cultured glioma cells in radioimmunoassay. One of these MAb's (AS AY1, immunoglobulin (Ig)(G1) lysed cultured glioma cells with human lymphocytes or murine macrophages as effector cells; the other MAb (AS-AY2, IgM) was reactive in complement-dependent cytotoxicity assay. These two MAb's therefore seem especially promising reagents in approaches to immunotherapy of human malignant glioma. PMID- 2585081 TI - Cytosolic calcium changes in endothelial cells induced by a protein product of human gliomas containing vascular permeability factor activity. AB - A vascular permeability factor (VPF) derived from serum-free conditioned medium of cultured human malignant gliomas (HG-VPF) has been described previously. The rapid kinetics of HG-VPF activity in an in vivo assay of vascular permeability suggests a direct action upon the vascular endothelial cell. To determine whether HG-VPF was capable of inducing a physiologically significant alteration in isolated endothelial cells, cytosolic calcium [Ca++]i was measured in vitro in these cells before and after their exposure to media containing this substance. This was accomplished by preloading cultured endothelial cells with a fluorescent intracellular Ca++ probe fura-2/AM. It was found that HG-VPF induced a rapid and transient elevation of [Ca++]i in normal endothelial cells derived from human umbilical vein, bovine adrenal medulla, bovine pulmonary artery, and rat brain. This effect was inhibited by chelating extracellular calcium [Ca++]e with ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetra-acetic acid (EGTA), indicating that the HG-VPF-induced response resulted from the influx of extracellular calcium. The addition of cations that act as nonspecific calcium channel blockers (Li+, Co++, Mn++, La ) completely inhibited VPF activity, further supporting the role of [Ca++]e influx. The HG-VPF activity was not, however, blocked by verapamil, a calcium antagonist that appears to be specific for voltage-gated calcium channels. Furthermore, exposure of endothelial cells to 120 mM [K+]e did not result in a calcium transient. Coincubation of endothelial cells with dexamethasone inhibited HG-VPF-induced rises in [Ca++]i, while having no effect upon cyclic nucleotide-induced changes in calcium. The present studies indicate that vascular extravasation induced by human glioma-derived VPF may be mediated by a direct action upon vascular endothelial cells. Furthermore, the observed dexamethasone-induced inhibition of this process suggests a specific cellular action for corticosteroids. This, together with previous observations that dexamethasone suppresses both the production of VPF by tumor cells in vitro and its permeability-inducing activity in vivo, may explain the efficacy of glucocorticoids in the treatment of neoplastic vasogenic brain edema. Finally, studies with a polycationic peptide (protamine) known to induce blood-brain barrier disruption in vivo revealed similar effects upon endothelial cytosolic calcium levels. As HG-VPF is a positively charged macromolecule, a common interaction between these substances and the negatively charged endothelial cell surface in the induction of permeability is suggested. Nonspecific cross-linking of charged groups of the endothelial glycocalyx and specific HG-VPF receptor binding are both valid mechanisms of HG-VPF-mediated calcium changes. Their potential relevance in the setting of microvascular permeability is discussed. PMID- 2585083 TI - Effects of nicardipine on the ex vivo release of eicosanoids after experimental subarachnoid hemorrhage. AB - The activation of lipid peroxidation and the enhancement of arachidonic acid metabolism have been demonstrated as indicators of brain damage after subarachnoid hemorrhage (SAH). Meanwhile, the final common pathway of neuronal damage seems to be related to the impaired homeostasis of Ca++. The present study evaluated the effect of the calcium-antagonist nicardipine on arachidonate metabolism after experimental induction of SAH. The ex vivo release of four eicosanoids (prostaglandin (PG)D2, PGE2, 6-keto-PGF1 alpha, and leukotriene (LT)C4) was measured at different intervals after SAH induction. Rats were separated into the following three groups: a sham-operated group, an SAH group (rats were injected with 0.3 ml autologous arterial blood), and an SAH-treated group (after SAH induction, rats were treated with nicardipine 1.2 mg/kg intraperitoneally). Nicardipine significantly decreased the ex vivo release of PGD2 at 48 hours after SAH (p less than 0.01). The release of PGE2 was significantly enhanced at 6 hours after SAH, while in the nicardipine-treated group PGE2 release is significantly reduced. Nicardipine also affects the lipoxygenase pathway, reducing the release of LTC4 at 1, 6, and 48 hours after SAH induction. The results of the present study show that nicardipine treatment exerts an inhibitory effect on both biochemical pathways of arachidonic acid metabolism; aside from vascular effects, nicardipine could exert a protective role against the release of arachidonate metabolites, which could play a significant role in the pathogenesis of brain damage after SAH. PMID- 2585084 TI - Effects of ML-9 on experimental delayed cerebral vasospasm. AB - Experimental delayed cerebral vasospasm was produced in a two-hemorrhage canine model. The spastic basilar artery was exposed via the transclival route under a surgical microscope and was dilated by the topical application of 1-(5 chloronaphthalenesulfonyl)-1H-hexa-1,4-diazepine (ML-9), a selective antagonist of myosin light chain kinase. Dilation was dose-dependent, with a median effective dose (+/- standard deviation) of 51.4 +/- 6.9 microM. In addition, 50 microM of ML-9 was injected into the cisterna magna until the intracranial pressure (ICP) reached 200 mm H2O for 30 minutes, including a complete reversal of angiographic delayed vasospasm in three of seven dogs; in contrast, 150 microM of ML-9 was infused at 1.52 ml/min into the vertebral artery for 30 minutes, producing little dilation of the spastic basilar artery. In another study, the intracisternal perfusion of 50 microM of ML-9 at 1.48 ml/min for 30 minutes in dogs with an ICP of less than 200 mm H2O produced no serious electroencephalographic abnormalities, and the mean arterial blood pressure and pulse rate remained normal; no neurological deficits or significant histological abnormalities ascribable to the intracisternal ML-9 were found. PMID- 2585085 TI - Microsurgical anatomy of the tentorial sinuses. AB - Variations of the tentorial sinus of cadaver cerebellar tentoria were examined under a surgical microscope. The tentorial sinuses were classified into four groups: Group I, in which the sinus received venous blood from the cerebral hemisphere; Group II, in which the sinus drains the cerebellum; Groups III, in which the sinus originates in the tentorium itself; and Group IV, in which the sinus originates from a vein bridging to the tentorial free edge. The tentorial sinuses of Groups I and II were frequently located in the posterior portion of the tentorium. The sinuses of Group I were short and most frequently present in the lateral portion of the tentorium. The tentorial sinuses of Group II, which were usually large and drained into the dural sinuses near the torcular, were separated into five subtypes according to the draining veins and direction of termination. The tentorial sinuses of Groups III and IV were located near the tentorial free edge or the straight sinus. The draining patterns of the tentorial sinuses and their draining veins (so-called "bridging veins") were present in most cases. Knowledge of this anatomy can benefit the neurosurgeon carrying out repair near or on the cerebellar tentorium. PMID- 2585086 TI - Intracerebral myiasis from Hypoderma bovis larva in a child. Case report. AB - Cerebral myiasis with a 10-day history of convulsions due to an intracerebral hematoma caused by a Hypoderma bovis larva is reported in an 8-year-old child. Computerized tomography (CT) showed the hematoma in a right parieto-occipital location. The H. bovis larva and the extensive intracerebral hematoma were discovered during surgery. Among human parasitoses, cerebral myiasis is rare: a review of the literature revealed only two reports, one published in 1969 and one in 1980. This is the first case that has been diagnosed as cerebral myiasis with exact identification of the Hypoderma bovis larva both from the CT scans and at surgery in a patient during life. PMID- 2585087 TI - Multiple dural arteriovenous malformations. Report of two cases. AB - Two cases of multiple dural arteriovenous malformations (AVM's) in different locations are reported. One patient was diagnosed as having a dural AVM involving the right cavernous sinus that disappeared spontaneously 4 months after onset of symptoms. After an interval of 4 months, another dural AVM appeared involving the right lateral sinuses (transverse and sigmoid sinuses) with occlusion of the right sigmoid sinus. In the other patient, multiple dural AVM's were demonstrated on angiography, one involving the cavernous sinus and the other the left lateral sinus. The frequency of multiple occurrence and possible mechanisms of sinus occlusion are discussed. PMID- 2585089 TI - Intervertebral disc embolization resulting in spinal cord infarction. Case report. AB - A case of spinal cord infarction resulting from embolization of fibrocartilaginous intervertebral disc material is presented. Cases from the literature are reviewed and the theories of pathogenesis are discussed, in all reported cases the diagnosis was not made until postmortem examination. PMID- 2585088 TI - Cavernous angioma of the tentorium cerebelli. Case report. AB - The case of a cavernous angioma of the tentorium cerebelli is described. This is the seventh reported case of a cavernous angioma in this unusual location and the first of a dural cavernous angioma demonstrated by magnetic resonance imaging. The clinical presentation, radiographic features, and surgical treatment of these rare tumors are discussed, along with a review of the literature. PMID- 2585090 TI - The "thousand-hands Kannon" universal headframe. Technical note. AB - The authors describe a new headframe system, by which a variety of instruments, such as brain retractors, suction tubes, mirrors, forks, armrests, and cotton sheet trays, can be simultaneously supported. This frame enables neurosurgeons to perform operations with greater ease and fewer problems. PMID- 2585091 TI - LP shunting in cases of Chiari malformation. PMID- 2585092 TI - Hypothermia and circulatory arrest in aneurysm surgery. PMID- 2585093 TI - Pneumatized anterior clinoid mimicking an aneurysm. PMID- 2585094 TI - Surgical management of spinal fractures. PMID- 2585095 TI - Scientific highlights of the European Association of Nuclear Medicine Congress- 1989. Nuclear medicine continues its innovative development. PMID- 2585096 TI - Nonimmunogenic hyperthyroidism: cumulative hypothyroidism incidence after radioiodine and surgical treatment. AB - During 1977, 246 hyperthyroid patients were seen in our departments, 140 (57%) with nonimmunogenic hyperthyroidism (NIH)--101 with a toxic adenoma (TA) and 39 with multifocal functional autonomy (MFA). All patients but one could be followed over 9 yr, 101 after 131I treatment (RIT), another 29 after surgery (S). Ten patients were left untreated. Thirty-four treated (24%) patients died, none as a result of thyroid or post-treatment complications. There was no hyperthyroidism later than 9 mo after therapy. Only 1% (RIT) and 24% (S) were hypothyroid 1 yr after treatment. But 19% of all treated NIH patients were hypothyroid after 9 yr or at the time of their death, 12% after RIT and 41% after S. The cumulative hypothyroidism incidences 1.4%/yr for RIT and 2.2%/yr for S, were not significantly different. Out of the five survivers without RIT or S, two TA patients were hypothyroid. The effect of RIT on goiter related loco-regional complications was not worse than after S. We conclude that RIT is the treatment for NIH, leaving surgery for exceptional cases. PMID- 2585097 TI - Diagnosis of coronary artery disease by radionuclide angiography: effect of combining indices of left ventricular function. AB - The aim of this study was to determine whether the diagnostic capability of radionuclide angiography (RNA) in detecting coronary artery disease (CAD) might be improved by using several indices of left ventricular (LV) function in concert. Three different models (rest data, exercise data, and rest plus exercise data) were derived by stepwise multivariate discriminant analysis of RNA data in 65 normal volunteers and 111 patients with CAD and normal ejection fraction (EF) at rest. The model with only resting indices yielded a diagnostic capability comparable to the simple measure of EF response to exercise (area under receiver operating characteristic curve = 89% and 91%, respectively). Both the exercise and rest plus exercise models gave better results (area = 94% and 97%, respectively), but only the rest plus the exercise model was better than the EF response alone (p less than 0.001). Thus (a) if resting studies alone are performed, the diagnostic potential of RNA may be improved by combining several indices of resting function; and (b) combined rest and exercise data may improve the sensitivity of RNA in detecting CAD over what could be obtained with the EF response to exercise alone. PMID- 2585098 TI - Effects of heart rate on myocardial thallium-201 uptake and clearance. AB - The effects of heart rate on the myocardial uptake and clearance of 201Tl were studied prospectively in seven healthy men, mean age 43 +/- 7 (s.d.) yr. Initial and delayed (3 hr) thallium images were obtained in three views after three bicycle exercise tests: to maximal, 80% and 60% of predicted maximal heart rate. The mean of three views initial myocardial 201Tl uptake was higher at maximal than at both 80% and 60% of predicted maximal heart rate, being 81% (p less than 0.01) and 60% (p less than 0.01) of maximal activity, respectively. The myocardial activity in the delayed images was identical. There was a linear relationship between heart rate and the initial myocardial activity, r = 0.86 (p less than 0.001). The mean (range) 201Tl clearance was 58% (51-65), 47% (34-56), and 34% (22-49) (all differences p less than 0.01), respectively. Concordance among the three individual views in estimating clearance was best for the highest exercise level. There was a linear relationship between heart rate and clearance, r = 0.80 (p less than 0.001). Clearance was altered by only 1.67 x 10%/heart bpm (0.024 hr/heart beat). Clearance in the liver, spleen and lungs increased at submaximal exercise levels. Thus, a linear relationship between heart rate and clearance is the result of changes in the initial exercise myocardial 201Tl activity. Submaximal exercise may reduce reproducibility of clearance estimation, and the change of myocardial clearance with heart rate seems less than previously suggested. PMID- 2585099 TI - Temporal changes in accumulation of N-isopropyl-p-iodoamphetamine in human brain: relation to lung clearance. AB - Temporal changes in brain uptake of 123I-labeled N-isopropyl-p-iodoamphetamine (IMP) were studied by means of a multi-detector single photon emission computed tomography (SPECT) scanner. Serial dynamic SPECT scan was performed for 50 min following an i.v. bolus injection of IMP in 30 patients with various neurologic diseases. In 18 of them the radioactivity in the lung was also recorded by a single probe detector during the serial dynamic SPECT scan. Brain activity showed a gradual increase after the injection of IMP, reaching 63 +/- 7% of the maximum activity at 5 min and 90 +/- 5% at 20 min. The lung clearance showed a large variation among the individual cases; 29 to 72% (52 +/- 11%) of the initial peak activity at 20 min and 22 to 57% (41 +/- 9%) at 50 min after the injection. A significant positive correlation was observed between the clearance half-time in the lung and the time to reach 90% of the maximum activity in the brain (r = 0.86, p less than 0.001). These results suggested that brain uptake of IMP is influenced by the lung clearance and the optimum time to start SPECT data acquisition using a conventional rotating gamma camera system is 20 min after the injection. PMID- 2585100 TI - Functional imaging of brain maturation in humans using iodine-123 iodoamphetamine and SPECT. AB - The application of regional cerebral blood flow (rCBF) study by means of lipophilic radiotracers and single photon emission computed (SPECT) devices in very young infants is hampered by the considerable changes of rCBF pattern as a result of the cerebral maturation process. In an attempt to determine the normal evolution of [123I]IMP SPECT pattern as a function of age, we retrospectively selected the studies of 30 babies with normal clinical examination, EEG and CT or ultrasound scans at time of SPECT. There was a marked predominance of the thalamic perfusion over cortical areas until the end of the second month. The distribution of regional cortical activity followed a strict sequence. The perfusion of both parietal and occipital areas was well-visualized around the 40th week of gestational age and thereafter rapidly rose, always, however, with a slight predominance of the parietal activity. At the opposite, frontal activity which remained scarcely recognizable up to the second month tremendously rose to present the adult-like pattern at the beginning of the second year. The rCBF changes described above are well in agreement with the behavioral evolution occurring during prime infancy. PMID- 2585101 TI - Model-based quantification of myocardial perfusion images from SPECT. AB - A system for quantitative analysis of myocardial perfusion tomograms is proposed. The system starts with an automated delineation of the total left ventricle, including possible perfusion defects, to determine the mass and shape of the myocardium. Next, polar maps or bulls-eyes are computed from the delineation, which can then be compared to reference bulls-eyes to detect perfusion defects. The proposed system differs in three main aspects from currently available bulls eye algorithms. First, radial slices are used rather than short-axis slices. In this way three-dimensional gradient information is retained, in particular near the base and the apex of the left ventricle. Moreover, the reproducibility of this method is expected to be superior, since the interactive selection of short axis slices through the left ventricle is eliminated. Second, the left ventricle is automatically delineated using a flexible computer model in order to obtain higher reproducibility. The resulting delineation contains both mass and shape information. Third, in addition to the classic count rate bulls-eye, a mass bulls eye is computed, which contains the myocardial mass corresponding to each bulls eye pixel. Analysis of the count rate bulls-eye reveals perfusion defects, the quantification of the defects is carried out with the mass bulls-eye. PMID- 2585102 TI - A model of the peritoneal cavity for use in internal dosimetry. AB - Several therapeutic and diagnostic techniques involve injection of radioactive material into the peritoneal cavity. Estimation of the radiation dose to the surface of the peritoneum or to surrounding organs is hampered by the lack of a suitable source region in the phantom commonly used for such calculations. We have modified the Fisher-Snyder phantom to include a region representing the peritoneal cavity which may be employed to estimate such radiation doses. A geometric model is described which is coordinated with the existing organ regions in the phantom. Specific absorbed fractions (derived by Monte Carlo techniques) for photon emissions originating within the cavity are listed. Photon S-values for several radionuclides which have been administered intraperitoneally are shown. Dose conversion factors for electrons irradiating the peritoneal cavity wall, from either a thin plane or volume source of activity within the cavity, are also given for several nuclides. PMID- 2585103 TI - Rapid and sensitive response of carbon-11-L-methionine tumor uptake to irradiation. AB - Evaluation of cancer treatments by the measurement of tumor size is an unsatisfactory method for the observation of the radiobiologic response of the tumor. After 20 Gy single-dose irradiation of 60Co to rat tumor AH109A, the L [methyl-11C] methionine tumor uptake, the microscopic extension of tumor necrosis and the shrinkage of tumor were compared quantitatively. L-[Methyl-11C]methionine uptake fell to 54 +/- 19% of non irradiated tumor at 12 hr after irradiation. Necrosis extended 49 +/- 7% of total tissue volume after 3 days. Tumor volume decreased 48 +/- 12% 10 days after irradiation. L-[Methyl-11C]methionine uptake by tumor showed a sharp and rapid linear decrease after irradiation and the response of the uptake to irradiation preceded the extension of necrosis and tumor shrinkage. We conclude that radiation effect on the tumor may be evaluated immediately after irradiation by the measurement of L-[methyl-11C]methionine uptake and thus clinical application of positron emission tomography may give a benefit to the patients undergoing radiotherapy. PMID- 2585105 TI - In vitro and in vivo evaluation of granulocyte labeling with [99mTc]d,1-HM-PAO. AB - The functional integrity of white blood cells labeled with [99mTc]d,1-HM-PAO containing variable amounts of the ligand or of the 99mTc activity was evaluated by enzymatic tests and by measuring random migration, chemotaxis, phagocytosis, killing, and adhesion. The ultrastructure of labeled cells was studied by electron microscopy. The tracer dose and the HM-PAO concentration did not significantly affect phagocytosis and killing. The results of the other tests remained normal. A maximum labeling efficiency of 80% was reached by incubating the granulocytes for 20 min with 10-20 mCi of [99mTc]d,1-HM-PAO containing 50 micrograms of the ligand in 1 ml of saline. There was only a slow washout of 20% of activity from the labeled cells in 24 hr. The ultrastructure was not influenced by the labeling technique. Proven infection sites of 17 orthopedic patients were clearly visualized. After a short transient lung uptake, there was a clear spleen and moderate liver uptake with early bladder and late prominent colon visualization. Because of the lower cost, favorable radiation dose and more suitable tracer characteristics, this technique is a promising alternative for 111In labeling of white blood cells. PMID- 2585104 TI - Imaging of inflammatory arthritis with technetium-99m-labeled IgG. AB - The accumulation of nonspecific polyclonal human immunoglobulin G (IgG) radiolabeled with 99mTc was compared to that of [99mTc]albumin and [99mTc]nanocolloid in rats with collagen induced arthritis. Serial scintigrams were acquired directly, 4 and 24 hr after injection. A clearly discernable image of the site of synovitis was seen with [99mTc]IgG as early as 4 hr postinjection. The relative intensity of the inflammatory lesion was maximal at 24 hr. Discrimination between arthritic and nonarthritic joints as well as correlations between the relative intensity of the arthritic joint and clinical indices of joint inflammation were superior with IgG compared to albumin or nanocolloid. These studies show that localization and severity of inflammatory joint disease can be detected with radiolabeled nonspecific IgG. PMID- 2585106 TI - Energy-weighted acquisition of scintigraphic images using finite spatial filters. AB - Energy weighted acquisition (EWA) is a technique for improving image contrast by correcting for some of the blurring effects of Compton scattering within the patient. We outline image formation theory as it applies to energy weighting and present a pre-processing implementation that acquires images with real-number energy-dependent weighting functions of finite spatial extent. The effect of scattered radiation on quantitative accuracy, with and without EWA, is demonstrated with sheet and point sources at various depths. A planar phantom and a clinical 201TI study demonstrate enhanced contrast and edge definition. The performance of EWA in SPECT is shown by 99mTc and 123I phantom studies and a clinical 125I study. PMID- 2585107 TI - Three-dimensional display of gated cardiac blood-pool studies. AB - There has been little interest in use of single photon tomography in gated cardiac blood-pool imaging. This fact arises most likely from two principal causes: the difficulty associated with interpretation of images presented as series of beating slices, and the formidable computational burdens involved in processing the data. We have addressed both of these issues. A new method, called volume rendering, is used to generate realistic and easily interpreted three dimensional images of the cardiac blood pool. These images of the beating heart can be displayed in a continuously rotating cine format or viewed in any orientation selected by the observer. Total computation time for a 16-frame gated study, including filtered backprojection, spatial and temporal filtering, and volume rendering, is 82.7 min employing a 32-bit computer and an array processor. With greater use of the array processor it should be possible to reduce the time to approximately 40 min, thus making routine use of these three-dimensional images clinically feasible. PMID- 2585109 TI - Irradiation of volunteers in nuclear medicine. PMID- 2585108 TI - Nuclear medicine imaging of systemic mastocytosis. AB - A 66-yr-old male with systemic mastocytosis is presented along with classic imaging findings of dense bone on radiographs, intense uptake on bone scan and marrow expansion on bone marrow scan. Dual photon absorptiometry (DPA) measurements of the skeleton revealed a very high bone mineral measurement of 1.678 grams per square centimeter (lumbar vertebrae 2 through 4). It is suggested that DPA may be useful to follow the development of mast cell disease in the bones. PMID- 2585110 TI - Gainsharing: rewarding nurse performance. PMID- 2585112 TI - The nurse advocate project: a strategy to retain new graduates. AB - Would you like to have 96% of the newly graduated nurses you hired last year still working for you a year later? Does your staff know how to help new graduates, who have been in the student role for over 20 years, adjust to the world of work? The author discusses the nurse advocate project which increased retention, decreased costs, and fostered a more positive work environment for all staff. PMID- 2585111 TI - Improving your written communications. AB - Writing letters and memos is a required task--welcome or not--of any administrator, and competition is fierce for an audience's attention and time. The authors offer a guide for improving organization of written messages through a time-saving technique called mapping and improving the message's style and tone through application of advice from the experts on writing clearly and concisely. PMID- 2585113 TI - Assessing communication in organizations. AB - Communication problems exist in every organization. Nurse administrators can address these problems by conducting a communication assessment. The author provides suggestions for developing a tool to assess the communication system of an organization. Data obtained from the assessment can provide the basis for improving communications. Potential outcomes of an improved communication system include increased satisfaction of nursing personnel and greater effectiveness of the organization. PMID- 2585114 TI - Discharge holding area: using inpatient beds more efficiently. AB - Unlike many private hospitals which are closing beds or have low census, one county hospital has an increase in the number of acutely ill patients who require admission. Frequently, bed availability is impeded by delays in final departure of discharged patients. A discharge holding area is an economical solution to expediting bed availability of discharged patients. Steps for developing such a unit and the outcomes are discussed. PMID- 2585115 TI - She is a man: avoiding sexist language. PMID- 2585116 TI - Service capacity management in ambulatory care clinics. PMID- 2585117 TI - Documentation principles and pitfalls. PMID- 2585118 TI - Current trends in freeze-fracture, part I. PMID- 2585119 TI - Counting and measuring IMPs and pits: why accurate counts are exceedingly rare. AB - Particle counting and measuring techniques are now widely used to characterize normal membranes and to identify molecular changes occurring during development, maturation, and aging during progression of disease and following pharmacological manipulation. However, the use of particle counting and measuring for the identification of molecular changes in membranes has been premature. We show that current procedures rarely yield replicas that are free of cryogenic or mechanical prefractures, and as a result, the "complementarity" of membrane faces is severely compromised. However, with simple alterations of procedure, combined with the resolve to recognize and discard images of pre-fractured membrane faces, a high degree of "complementarity" may be obtained. Criteria for recognizing the occurrence and relative frequency of noncomplementarity are presented and a cleaving method for avoiding a primary source of water vapor contamination is described. In such replicas, membrane pits are found in equivalent numbers and near-identical diameters as the intramembrane particles (IMPs) in the complementary-type membrane faces. When conditions of "cold fracture" and immediate replication are demonstrated, fracture faces are minimally contaminated by frozen water vapor, yielding images where 1) diameters of IMPs vs. pits are very nearly identical, 2) large diameter IMPs are very rare, and 3) the numbers of IMPs and pits are increased substantially over the numbers currently reported. Thus, we reiterate previous proposals that complementarity of membrane faces is the single most important criterion that must be met before accepting the validity of IMP counts or for attributing perceived changes in IMP density or size to conditions of experimental manipulation, to normal developmental processes, or to disease etiology. PMID- 2585120 TI - Quick-freeze, deep-etch, rotary-shadow views of the extracellular matrix and cortical cytoskeleton of Xenopus laevis eggs. AB - The quick-freeze, deep-etch, rotary-shadow technique provides a powerful tool to study the structural dynamics of extracellular matrices. Using this technique, we show that the extracellular investments of the Xenopus laevis egg are multilayered and securely anchored to the egg surface. The cortical cytoskeleton within the egg contains embedded cortical granules with surrounding endoplasmic reticulum and is capped by a thin reticular sheet that contacts the inner surface of the plasma membrane. The extracellular matrix undergoes three distinct changes at fertilization: a) formation of a "smooth" layer below the vitelline envelope (VE), b) transformation of the VE itself to an altered VE composed of concentric fibrous sheets, and c) formation of a dense, "briar-patch"-like fertilization layer at the upper surface of the VE. PMID- 2585121 TI - Protocol for 3-D visualization of molecules on mica via the quick-freeze, deep etch technique. AB - Molecular imaging by freeze-drying of molecules adsorbed to a mica substrate often provides better images of molecules than those attainable with other methods; the images are easier to interpret than those obtained with frozen thin film or negative staining, and the 3-dimensional information content is greater. The complete procedure for the production and examination of platinum-carbon replicas of molecules is described. Topics include production of a mica flake suspension, chemical pretreatment of the flakes to enhance adsorption, quick freezing of the samples on mica, optimal operation of the freeze-fracture equipment, and orientation of replica topography. The production of stereo micrographs is analyzed in detail, with emphasis on the photographic procedures necessary for interpretation and on the identification of correct micrograph orientation. Guidelines are provided for the extrapolation from observed molecular size in platinum replicas to expected molecular weight. PMID- 2585122 TI - A method for obtaining light microscopic survey sections from fresh frozen tissue during cryoultramicrotomy. PMID- 2585123 TI - Flat mold embedding with LR white and Lowicryl K4M. PMID- 2585124 TI - Polystyrene specimen support films for the collection of ultrathin serial sections. PMID- 2585125 TI - Repairing holes and tears in the plastic substrates on slot grids. PMID- 2585126 TI - Transmission electron microscopy of the cytoskeleton of migratory and invasive cells. PMID- 2585127 TI - Improved shielding for energy-dispersive X-ray microanalysis in the high-voltage electron microscope. PMID- 2585129 TI - Effect of colostomy on nitrogen nutrition in the chicken fed a low protein diet plus urea. AB - Recent interest in the role of the ceca in avian nutrition has focused on recycling of urinary nitrogen through the ceca. In the colostomized chicken, we observed appreciable decrease in utilization of dietary urea nitrogen. This is the first report demonstrating that the ceca are able to play an advantageous role in nitrogen nutrition of the chicken, because back-flow of urinary nitrogen into the ceca was completely inhibited by colostomy. When colostomized chickens were fed a diet containing urea, little urea was found in feces but the amount of urea excreted in the urine corresponded to 77.5% of urea intake. Droppings of normal control chickens fed the same diet did not contain urea. However, they contained twice as much ammonia as the urine plus feces of colostomized chickens, indicating active and great degradation of urinary urea to ammonia by microflora in the ceca of control chickens. The recycling of urinary nitrogen through the ceca may be involved in the utilization of dietary urea by the chicken. PMID- 2585128 TI - Biotin analysis of commercial vitamin and other nutritional supplements. AB - Because previous observations suggest that biotin may be present in vitamin preparations not labeled as containing biotin, we determined the biotin content of several over-the-counter vitamin and nutritional supplements said to contain biotin (group 1) and several in which biotin content was not specified (group 2). Biotin concentration was measured using the 125I-avidin assay which detects total avidin-binding substances. Water extracts were assayed for free biotin and acid hydrolysates were assayed for total biotin. The results of the 125I-avidin assay agreed with the stated biotin content for most vitamin and nutritional supplements in group 1. Biotin was the only avidin-binding substance in the preparations from group 1, based on reversed-phase chromatography. However, some vitamin and nutritional supplements in group 2 contained nutritionally significant amounts of biotin, particularly if the supplement contained liver or yeast extract. Total biotin was significantly higher than free biotin in one supplement; the difference was attributable to release of biotin rather than a biotin analog. We conclude that biotin may be present in some vitamin and nutritional supplements not labeled as containing biotin; biotin intake might be under-estimated if the subject is receiving a nutritional supplement containing extracts of liver or yeast. PMID- 2585130 TI - Altered cytoskeletal organization and secretory response of thrombin-activated platelets from copper-deficient rats. AB - The cytoskeletal organization that occurs following thrombin-induced activation of platelets was investigated in rats consuming either a copper-deficient diet containing less than 1 microgram Cu/g or a copper-adequate diet containing 5.5 micrograms Cu/g. Within 30 s following thrombin activation, the amount of polymerized actin in Triton X-100 extracts of whole platelets from copper deficient rats was greater than the amount in platelets from copper-adequate rats. Electrophoretic analysis of the cytoskeletal proteins obtained from low speed centrifugation of the Triton X-100 extracts indicated that the myosin content of the cytoskeleton increased with time and reached higher levels following activation in platelets from copper-deficient rats. Actin content of the cytoskeleton also increased with time following activation. However, the difference in cytoskeletal actin content of platelets from copper-deficient and copper-adequate rats was not as great as that observed for myosin. The rate of ATP secretion from thrombin-activated platelets was also increased by copper deficiency. Myosin association with the platelet cytoskeleton may be involved in platelet secretion following thrombin activation. Thus, the increased association of myosin with the cytoskeleton and concomitant increase in ATP secretion suggest that the normal mechanism for stimulus-response coupling is altered in thrombin activated platelets from copper-deficient rats. PMID- 2585131 TI - Fluoride absorption from the gastrointestinal tract of rats. AB - The contribution of the stomach and the small intestine to absorption of fluoride from the gastrointestinal tract was examined in rats. Fasted adult male rats weighing approximately 350 g were given 50 micrograms of fluoride in 1 ml of water by stomach intubation, with 14C-labeled polyethylene glycol as a marker of water movement through the gastrointestinal tract. Rats were killed at intervals up to 120 min, and the stomach, duodenum, jejunum, ileum, distal ileum and cecum were rapidly clamped and removed for fluoride analysis and 14C counting. Approximately 90% of the fluoride dose was absorbed in 120 min. Peak plasma fluoride concentration occurred 10 min after intubation and began to decline after 40 min as the rate of fluoride absorption slowed. Absorption from the stomach was derived from rates of gastric emptying and remaining fluoride. Even at 10 min after intubation, when the bulk of the fluoride remained in the stomach, only approximately 25% of fluoride absorption had occurred from the stomach and 75% from the small intestine. After 120 min, 19.8% of total fluoride absorption had occurred from the stomach. Although the stomach is unquestionably a significant site for fluoride absorption, its contribution is much smaller than that of the small intestine. PMID- 2585133 TI - An in vitro study of the effect of picolinic acid on metal translocation across lipid bilayers. AB - The effect of picolinic acid (pyridine-2-carboxylic acid) on the efflux of divalent metal ions from multilamellar liposomes was examined to determine the possible specificity and mechanism for its reported beneficial effects on the intestinal absorption and systemic metabolism of zinc. Extraliposomal picolinic acid increased the efflux of Zn, Cu, Co, Mn, Ni, Cd, Pb, Fe(II) and Ca from the vesicles. However, when picolinic acid was trapped with Co, Cu and Zn within the liposomes, the loss of metals was reduced. In a partition study, picolinic acid increased the aqueous solubility of Zn, Cu, Co and Cd at alkaline pH, but did not transfer the metal to an organic bulk phase of chloroform. It is proposed that picolinic acid does not act as an ionophore and that any effect it may have on zinc metabolism is dependent upon its unselective chelating properties, which may also lead to altered dietary and systemic compartmentation of other divalent cations. PMID- 2585132 TI - Phosphorus-induced nephrocalcinosis and kidney function in female rats. AB - The question was addressed whether dietary phosphorus-induced nephrocalcinosis in rats is associated with impaired kidney function. Weanling female rats were fed purified diets containing either 0.4 or 0.6% (wt/wt) phosphorus for 28 d. The diet containing 0.6% phosphorus produced marked kidney calcification, as determined both by chemical analysis of kidney calcium and histological examination in kidney sections. Histological examination did not show calcification in stomach, lung, heart or thoracic aorta, which are predisposition sites of metastatic calcification in secondary renal hyperparathyroidism. In rats fed the 0.6% phosphorus diet, phosphorus retention and urinary excretion were greater compared with rats fed the 0.4% phosphorus diet. The following indicators of kidney function were examined: water intake, urinary volume, urine and plasma osmolality, urine and plasma creatinine, urine and plasma urea, urea and creatinine clearance and urinary albumin excretion. Of these indicators, only urinary albumin excretion was significantly increased in rats fed the nephrocalcinogenic diet. In a further experiment, the increase of urinary albumin was reproduced. After pooling the results of the two experiments, in individual rats fed the 0.6% phosphorus diet, the concentration of kidney calcium was found to be positively related with kidney weight expressed relative to body weight (r = 0.82, n = 22) and with albumin excretion in urine (r = 0.79, n = 28). The increased weight of calcinotic kidneys was mainly due to both calcium deposition and tubular hyperplasia. It is concluded that dietary phosphorus-induced nephrocalcinosis is associated with impaired kidney function in rats. PMID- 2585134 TI - Calculation of zinc absorption in humans using tracers by fecal monitoring and a compartmental approach. AB - Zinc absorption is often determined following oral administration of tracer by fecal monitoring as dose minus tracer excreted in feces. The value obtained for absorption with this method is influenced by excretion of absorbed tracer into feces during the fecal collection period and by any incomplete elimination of unabsorbed tracer. In the present study a published, physiologically based compartmental model of zinc metabolism has been used to calculate, after oral tracer administration, the fecal appearance of unabsorbed and absorbed tracer and the appearance when fractional rates of endogenous excretion and elimination were varied. Absorption was determined by fecal monitoring and compared to the value determined using parameter values of the compartmental model. The value calculated for absorption using fecal monitoring varied with length of fecal collection, rate of excretion of absorbed tracer (secretion) and rate of elimination of unabsorbed tracer. Absorption was determined correctly by fecal monitoring only when the amount of absorbed tracer excreted was equivalent to the amount of unabsorbed tracer remaining in the gut. Fecal monitoring determines a parameter representing the combined processes of absorption, endogenous excretion (or secretion) and fecal elimination. PMID- 2585135 TI - Effects of starch, sucrose, fructose and glucose on chromium absorption and tissue concentrations in obese and lean mice. AB - Forty-eight male genetically obese (OB) mice (C57BL/6J-OB) and 48 lean male littermates were randomly assigned within main plots (OB or lean) to one of eight diets. Diets were low chromium or supplemented with 1 mg chromium as CrCl3 per kg. Starch, sucrose, fructose or glucose comprised 50% of the diet, which met AIN recommendations except for chromium. Experimental diets and deionized water were available ad libitum for 26 d. Mice were fasted 10 h and were intubated 2 h before killing with 15 microCi of 51CrCl3 in a 25% carbohydrate solution (2 mg carbohydrate/g body wt) of either starch, sucrose, glucose or fructose corresponding to the diet previously fed. 51Cr concentrations were significantly higher in the blood, liver, spleen, epididymal fat pad, testes and femur of animals given their carbohydrate load as starch than in animals fed sucrose, fructose or glucose. Carbohydrate had a significant effect on chromium concentrations of testes, spleen, kidney and liver with values generally being higher with the starch diet. Chromium supplementation increased bone and kidney chromium concentrations and heart and muscle glycogen. These data indicate that the source of carbohydrate can alter chromium absorption and retention. PMID- 2585136 TI - Effect of dietary taurine on renal taurine transport by proximal tubule brush border membrane vesicles in the kitten. AB - Renal adaptation of the kitten to altered dietary taurine intake was assessed using proximal tubule brush border membrane (BBM) vesicles. Three groups of kittens were adapted to purified diets containing 43.5% soy protein that were either taurine-free (OT) or contained 0.15% taurine (NT) or 1.0% taurine (HT). The plasma taurine concentration of the kittens fed OT decreased from 104 +/- 25 microM to 16 +/- 5 microM and 1.7 +/- 0.5 microM in 1 and 6 wk, respectively. Feeding HT increased plasma taurine concentration to 350 +/- 116 microM in 1 wk. Compared to NT, taurine accumulation by BBM vesicles was significantly elevated after 4 wk of feeding OT and decreased after 2 wk or less of feeding HT (P less than 0.05). Maximum renal adaptation occurred by 6 wk of feeding OT (206% increase in taurine uptake/15 s compared to NT) and by 2 wk or less of feeding HT (43% decrease in taurine uptake/15 s compared to NT). Evaluation of transport kinetics using renal cortex from groups of four kittens (16 determinations) fed NT, OT (12 wk) or HT (10 wk) revealed a Vmax of 55 +/- 10, 123 +/- 24 or 39 +/- 7 pmol.mg protein-1.10 s-1 and a Km of 32 +/- 7, 16 +/- 2 or 37 +/- 8 microM, respectively. The differences in Vmax and Km were significant between NT and OT (P less than 0.05), but not significant between NT and HT (P greater than 0.05). Our results suggest that renal adaptation of the kitten to changes in dietary taurine occurs with modifications of both Vmax and Km of the taurine transport system. PMID- 2585137 TI - Identification of transferrin as the major plasma carrier protein for manganese introduced orally or intravenously or after in vitro addition in the rat. AB - It is known that the metabolic handling of manganese (Mn) introduced via the diet or by intravenous injection is quite different. We hypothesized that this difference could be due in part to different proteins carrying Mn in plasma that could affect tissue uptake and retention. To test this idea, 54Mn was administered orally or intravenously to rats, and blood samples were taken by cardiac puncture at various time points postdosing. Plasma proteins were separated using fast protein liquid chromatography with a combination of anion exchange and gel filtration columns. Using these methods, independent of the route of 54Mn administration, transferrin was identified as the major Mn-binding protein in plasma. The identity was further confirmed by SDS-polyacrylamide gradient gel electrophoresis and Western blotting. These results conclusively show that 54Mn in plasma is carried by transferrin, regardless of route of administration and time postdosing. PMID- 2585138 TI - Effect of gender on the response to a high fat diet in aging Fischer 344 rats. AB - The purpose of this study was to describe the effects of high fat (HF) and low fat (LF) diets in male and female Fischer 344 (F344) rats ages 5, 23 and 27 mo. Rats were fed the diet for 3 mo, and then resting metabolic rate, body composition and adipose tissue cellularity were evaluated. Although body mass was greater in rats fed the HF diet, this difference was due to a rapid increase in mass within the first 2 wk. There was no difference in the rate of body mass gain after this period. Resting mass-independent metabolic rate did not significantly differ due to age, diet or gender. In general, percentage fat mass was greater in rats fed the HF diet and in female than in male rats in both diet groups. However, lean body mass (%) was not altered due to diet or age. Cell number of the retroperitoneal depot increased with age and diet between 5 and 23 mo of age in both male and female rats. There was no effect of age, diet or gender on retroperitoneal cell size or gonadal cell number and size. These data suggest that age, gender and diet do not significantly alter the ability of F344 rats to regulate body composition or fat cell proliferation. PMID- 2585139 TI - Effects of chronic ethanol and diet treatment on urinary folate excretion and development of folate deficiency in the rat. AB - Because the folate deficiency of chronic alcoholism has been proposed to result from ethanol-induced effects on metabolism or urinary excretion of folate, the present study was designed to evaluate the role of chronic ethanol-induced urinary folate loss on folate homeostasis in the rat. Male Sprague-Dawley rats were fed nutritionally sufficient liquid diets for 12 wk with or without ethanol, folate and sulfonamide. Urinary folate excretion was increased in ethanol-fed rats consuming folate-containing diets, but not in rats fed folate deficient diets. Consumption of folate-deficient diets led to a rapid decrease in urinary folate excretion, suggesting renal adaptation to conserve folate. Tissue and plasma levels of folate were mostly unaffected by ethanol ingestion in rats fed folate-containing diets. Ethanol treatment did not consistently enhance tissue folate depletion in rats fed folate-deficient diets. The results suggest that in rats consuming diets containing high levels of folate, chronic ethanol ingestion increased urinary folate excretion, but not to a sufficient magnitude to consistently affect folate homeostasis. PMID- 2585140 TI - Effects of acute ethanol on urinary excretion of 5-methyltetrahydrofolic acid and folate derivatives in the rat. AB - Acute ethanol treatment enhances the urinary excretion of endogenous folate. This effect has been implicated in the development of folate deficiency associated with chronic alcoholism. Previous studies have shown that urinary excretion of total [3H]-label after administration of [3H]folic acid is slightly higher in ethanol-treated rats because of conversion of the tracer to forms whose excretion is not affected by ethanol. Since [3H]folic acid is not the physiological substrate for the kidney, studies were performed using a high specific activity 5 methyltetrahydrofolic acid ([3H]5-CH3-H4 folic acid). Male Sprague-Dawley rats were given four consecutive hourly doses of ethanol at 1 g/kg, followed by infusion of [3H]5-CH3-H4 folic acid at 5 h. Urine samples were collected to 6 h, when rats were killed, and plasma, liver and kidney samples were collected. Endogenous urinary folate excretion and the fractional urinary excretion of both endogenous and [3H]5-CH3-H4 folic acid at the 5-6 h time period were significantly higher in ethanol-treated rats. The kidney had a tenfold greater specific incorporation of [3H]-label than did the liver. High performance liquid chromatography (HPLC) analysis of the plasma obtained at 6 h showed that 68% of the label was [3H]5-CH3-H4 folic acid, and HPLC analysis of the urine obtained from 5-6 h showed that only 10% of the label was [3H]5-CH3-H4 folic acid. The data indicate that [3H]5-CH3-H4 folic acid was rapidly taken up by the kidney and metabolized to other folate and nonfolate forms, which were then secreted into the renal tubule for excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585141 TI - Effect of dietary restriction on receptor-mediated and independent catabolism of beta-very low density lipoproteins in cholesterol-fed rabbits. AB - This study was designed to define the effect of dietary restriction and cholesterol feeding on disturbances of very low density lipoprotein (VLDL) catabolism. Three groups of 15 New Zealand rabbits were fed standard or cholesterol-rich diets either ad libitum or in restricted amounts and in vitro binding assays on hepatocyte membranes were carried out after 4, 8, 12 and 20 d. Cholesterol feeding reduced the specific binding of labeled beta-VLDL to liver membranes. Dietary restriction, which enhances the hypercholesterolemia induced by cholesterol feeding, had no additional effect on the down-regulation of beta VLDL specific binding. In another set of experiments the uptake of labeled beta VLDL by various tissues was measured after 15 d of feeding the diets. Cholesterol feeding decreased uptake of these lipoproteins by the liver and various extrahepatic tissues, such as skin, intestine, muscle, adipose tissue, kidneys, spleen and aorta. Additional changes occurred in liver and intestine with dietary restriction. In liver beta-VLDL uptake in the group fed a restricted amount of the cholesterol-containing diet was 70% of that in the group fed the same diet ad libitum. Taken together, the results suggest that dietary restriction acts mainly on the receptor-independent catabolism of beta-VLDL. PMID- 2585142 TI - Route of delivery of phenylalanine influences its effect on short-term food intake in adult male rats. AB - The effect of phenylalanine (Phe) on plasma and brain Phe and tyrosine (Tyr) levels and on short-term food intake in male rats was measured after intragastric (i.g.), subcutaneous (s.c.) and intraperitoneal (i.p.) administration. Compared to equimolar alanine (Ala), which served as the control, Phe significantly suppressed feeding at a dose of 90 mg/kg body wt when given i.p., but doses up to 720 mg/kg body wt had no effect when given i.g. or s.c. The high doses of Phe given by the i.g. or s.c. route resulted in higher levels of Phe in both plasma and brain than those following i.p. injection (90 mg/kg body wt). Furthermore, brain Tyr levels after i.g. Phe (720 mg/kg body wt) were equal to or higher than after i.p. Phe (90 mg/kg body wt). We conclude that the route of administration is an important variable influencing the effects of Phe on feeding behavior, and that these effects are not readily explained by plasma or brain Phe and Tyr concentrations. PMID- 2585143 TI - Bone marrow and serum concentrations of 25-hydroxyvitamin D, 24,25 dihydroxyvitamin D, and 1 alpha,25-dihydroxyvitamin D in patients with leukemia and normal subjects. AB - Concentrations of 25-hydroxyvitamin D (25-OH-D), 24,25-dihydroxyvitamin D [24,25(OH)2D], and 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] in bone marrow and serum of patients with leukemia and normal subjects were assayed. There were highly significant correlations between the bone marrow and serum concentrations of the respective vitamin D metabolites. Especially, the concentrations of 25-OH D and 1,25(OH)2D in the bone marrow gave very similar values to those in serum. This is a big advantage in controlling the bone marrow levels of vitamin D metabolites in patients with leukemia, because doctors can calculate the bone marrow levels from the serum levels of the respective vitamin D metabolites without bone marrow aspiration. When 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) was administered orally to eight patients with leukemia, clinical conditions were improved in seven patients: four complete remissions (CR), one partial response (PR), and two minor responses (MR) without severe hypercalcemia. The results suggest that the therapy with 1 alpha-OH-D3 is fairly effective for curing human leukemia although it is not dramatic. PMID- 2585144 TI - Concentrations of vitamin D-binding protein and vitamin D metabolites in plasma of patients with liver cirrhosis. AB - Plasma levels of vitamin D-binding protein (DBP) and vitamin D metabolites in patients with decompensated and compensated liver cirrhosis were assayed. Plasma levels of DBP in the decompensated group were significantly lower than those in the compensated group, but both were lower than the normal range. The plasma levels of 25-hydroxyvitamin D (25-OH-D) and 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] in the compensated group were within the respective normal ranges, whereas both values in the decompensated group were significantly lower than those in the compensated group. Most of 25-OH-D (higher than 96%) was confirmed to be circulated as a bound form with DBP in the plasma of not only the compensated but also the decompensated group. When vitamin D2 was given to the decompensated group, a significant increase of 1,25(OH)2D levels in the plasma could not be observed while 25-OH-D levels were increased. On the other hand, the administration of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) to the decompensated group caused a significant increase in the plasma levels of 1,25(OH)2D. Therefore, we suggest that the administration of 1 alpha-OH-D3 is useful for the treatment of bone disease induced by liver cirrhosis. PMID- 2585145 TI - Simple method of tocopherol determination in plasma lipoprotein fractions using a heparin-Ca precipitation technique. AB - A simple and convenient method using a heparin-Ca precipitation technique, which was devised for determination of serum lipoprotein fractions, was applied to the determination of tocopherol concentrations in individual lipoproteins. Three types of precipitates were prepared from 0.25 ml serum samples plus 0.1 ml of 5% heparin by mixing at 37 degrees C for 30 min with 5 ml of 0.054 M CaCl2 only, 0.054 M CaCl2 in 0.6% NaCl, or 0.054 M CaCl2 in 0.92% NaCl. These three precipitates consisted of chylomicron + VLDL (very low-density lipoprotein) + LDL (low density lipoprotein), chylomicron + VLDL, and chylomicron only, respectively. The tocopherol content of individual lipoproteins was calculated from the concentrations of tocopherol in these three precipitates, and the values obtained by using this technique were very close to those by a standard ultracentrifugation method. Thus, this simple method appears to be suitable for rapid tocopherol assay of a large number of samples. PMID- 2585146 TI - Tocopherol distribution in serum lipoproteins with respect to red blood cell tocopherol levels in children. AB - The relation of lipoprotein tocopherol levels to red blood cell (RBC) tocopherol was investigated in 81 healthy children, comprising 44 males and 37 females, using a new technique for separation of individual lipoprotein fractions. 1. In children there were no age and sex differences in tocopherol contents among individual lipoprotein fractions. The tocopherol content of high density lipoprotein (HDL) was slightly higher than that of low density lipoprotein (LDL), but this difference was not statistically significant. 2. The tocopherol content of HDL fractions was closely correlated with RBC tocopherol concentration, but there was no relationship in tocopherol levels between RBC and LDL and between RBC and very low density lipoprotein (VLDL). 3. There were no age and sex differences in contents of total cholesterol (T-ch), triglycerides (TG), phospholipids (PL), total lipids, HDL-cholesterol, LDL or VLDL in children. PMID- 2585148 TI - Different effects of bile and sodium taurocholate on mucosal calcium accumulation and calcium absorption in rats. AB - To demonstrate different effects of bile and Na taurocholate on calcium absorption, in vivo studies and in situ intestinal loop experiments were performed in intact rats. Only bile (collected from donor rats), but not 15 mM Na taurocholate, significantly increased the jejunal mucosa calcium and 45Ca contents after an intragastric administration of test solution containing 7.5 mM CaCl2 + 45Ca. However, plasma radioactivity which represented lumen to plasma calcium transport was increased by Na taurocholate but not bile, suggesting that both agents enhanced calcium transport across the brush border membrane but in the presence of bile some calcium remained in the mucosal cells. Results from the in situ studies supported the above findings. It was shown that bile and Na taurocholate enhanced the calcium transport from the lumen. However, net absorption was unchanged due to concurrent increase in the efflux of calcium. PMID- 2585147 TI - Changes in the concentrations of vitamin D and its metabolites in the plasma of healthy subjects orally given physiological doses of vitamin D2 by multivitamin or vitamin D preparations. AB - Changes in the concentrations of vitamin D and its metabolites in plasma of healthy subjects orally given physiological doses of vitamin D2 by multivitamin or vitamin D liquid preparations were determined and the bioavailability of vitamin D was studied. Separative assay on the D2 and D3 compounds of vitamin D, 25-hydroxyvitamin D (25-OH-D), 24R,25-dihydroxyvitamin D [24,25(OH)2D], and 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] was performed in plasma of eight healthy male volunteers. When the concentrations of vitamin D and its metabolites in plasma of volunteers were assayed after daily oral administration of 400 IU of vitamin D2 in a form of multivitamin tablet for 1 week, the variations of vitamin D3 and its metabolites in plasma levels were very small. In contrast, the concentrations of 25-OH-D2 and 1,25(OH)2D2 slightly increased after the administration, while neither vitamin D2 nor 24,25(OH)2D2 was detected. A single dose of 4,000 IU of vitamin D2 was orally given to the volunteers in a form of a vitamin D liquid preparation and the hourly variations were observed during 24 h. These concentrations of vitamin D2, 25-OH-D2, and 1,25(OH)2D2 were slightly higher than those of the repeated doses. The result suggests that even the high dose of 4,000 IU has little effect on the plasma levels of vitamin D2 and its metabolites by a single dose, indicating a low risk for hypervitaminosis D. PMID- 2585150 TI - Effects of dietary pantethine levels on drug-metabolizing system in the liver of rats orally administered varying amounts of autoxidized linoleate. AB - The effects of dietary pantethine levels on the drug-metabolizing system were investigated under administration of varying amounts of autoxidized linoleate (AL) with rat liver microsomes and S-9 fractions. AL having 800 meq/kg of peroxide value and 1,700 meq/kg of carbonyl value was dosed to the rats of each group given drinking water containing 0 mg% (deficient), 6.25 mg% (normal), and 125 mg% pantethine (sufficient). The contents and activities of the enzymes in the drug-metabolizing system in the rat liver of each pantethine-level group changed essentially in a similar manner, that is, they were induced at an AL daily dose of 0.2 ml/100 g body weight (i.e., small dose) for 5 successive days and lowered at a daily dose of 0.4 ml/100 g body weight (i.e., large dose) by the same administration period, compared with respective non-AL groups in each of the three pantethine levels. In both non-AL and the small-dose AL, enzyme activities of the electron transfer system in rat liver microsomes, aminopyrine-N demethylase activity, and metabolic activation of 2-acetylaminofluorene in S-9 fractions were significantly higher in the pantethine-deficient group than in the pantethine-normal and -sufficient groups. In the large-dose AL, the enzyme activities in the drug-metabolizing system decreased significantly in any pantethine levels, though the survival rate of the rats was higher in the pantethine-sufficient group than in the pantethine-normal groups. The results suggest that the pantethine relieves the effect of dosed AL on the drug metabolizing system in rat liver. PMID- 2585149 TI - Effects of cholesterol feeding on the distribution, metabolism, and accumulation of pentachlorobenzene in rats. AB - To investigate the influence of cholesterol content in tissue on the distribution, metabolism, and accumulation of pentachlorobenzene (PECB), rats were fed on a cholesterol-enriched (CHE) diet or a basal diet for 4 weeks. At two weeks, a single dose or a 6-day dosage of PECB was orally administered. The serum cholesterol concentration in the CHE diet group was 2.1-2.9 times higher than that in the basal diet group, while the serum triglyceride concentration decreased. The serum lipid levels were similar to the levels at two weeks. The blood PECB concentration was not different between the two groups. Increases in the contents of PECB and lipid in tissue due to the CHE diet feeding were observed only in liver (PECB, 2.6-3.0 times; triglyceride, 2-3 times; cholesterol, 10-15 times). Content of pentachlorophenol, a main metabolite of PECB, and the level of drug-metabolizing enzymes in liver of the CHE diet group tended to be higher than those of the basal diet group. These results suggested that the increase in PECB accumulation in the liver of the CHE diet group was not due to the decrease of PECB metabolism but due to the increase in the content of cholesterol and triglyceride. PMID- 2585151 TI - Lesions of intestinal epithelium by ingestion of bean lectins in rats. AB - Wistar rats were submitted to the action of active lectins from common dry beans (Phaseolus vulgaris) and from jack beans (Canavalia ensiformis, DC). Raw common bean was offered to the rats in an otherwise balanced diet to make 10% protein as the sole protein source. A single dose of 20 mg of jack bean lectin (concanavalin A) was given by gastric intubation. Half of the rats receiving raw bean died within 22 days of experiment. Histological findings showed ulceration and necrosis of the intestinal villi in the surviving rats. In some cases the lesions reached also the submucosa. Gastric intubation of concanavalin A caused intense scaling off in the apical portion of the villi. PMID- 2585152 TI - Effects of addition of sulfur-containing amino acids and glycine to soybean protein and casein on serum cholesterol levels of rats. AB - The effects of the supplementation of methionine (Met), cystine (Cys), and glycine (Gly) to soybean protein or casein on serum and liver lipid levels were studied in rats. Rats were fed cholesterol-free diets containing 25% soybean protein or casein supplemented with 0.75% Met, 2.5% Gly, or a combination of these two for 4 weeks. The addition of Met to soybean protein caused a significant increase in serum cholesterol and this was slightly ameliorated when Gly was given simultaneously. In rats fed casein diets, serum cholesterol tended to decrease when Gly, or Met and Gly were added. A simultaneous supplementation of Met and Gly to casein resulted in a reduction of hepatic cholesterol. Cystine added at the 0.6% level did not cause demonstrable changes in lipid concentrations except for a drop in serum triglyceride of the casein group. When 2.0% Gly was added to cholesterol-enriched diets containing 20% protein, serum cholesterol decreased significantly only when the protein source was casein and the level attained was comparable to that observed in rats fed soybean protein. Liver cholesterol was also markedly decreased by the addition of Gly to casein. The results suggest a possible role of Gly in the regulation of serum cholesterol levels by dietary protein. PMID- 2585153 TI - Effects of sitosterol and sitostanol on micellar solubility of cholesterol. AB - The influence of sitosterol and sitostanol on the solubility of cholesterol in mixed bile salt micelles in vitro and in vivo was investigated to examine the mechanism by which sitostanol inhibits cholesterol absorption more than does sitosterol. Both sitosterol and sitostanol decreased micellar solubility of cholesterol to a similar extent, when determined with the turbidity. Also, these sterols reduced the concentration of cholesterol in micelles, both in vitro and in vivo. The extent of the reduction of micellar solubility of cholesterol by these sterols was almost the same in vitro, whereas sitostanol tended to reduce the solubility more effectively than sitosterol in vivo. Thus, the interference with cholesterol solubilization in vivo may be responsible for effective inhibition of cholesterol absorption by sitostanol. Since the effect of sitostanol was not observed in vitro, there is a possibility that another factor(s) not included in the in vitro system might affect the action of sitostanol on micellar solubility of cholesterol in vivo. PMID- 2585154 TI - Changes in the basal metabolic rate of a normal woman induced by short-term and long-term alterations of energy intake. AB - A long-term experiment was carried out to study the effects of alterations in energy intake and meal contents on basal metabolic rate (BMR) of a normal woman. Alterations of energy intake induced changes in BMR and pulse rate in addition to body weight changes. Whether BMR was expressed per whole body, per unit body weight, or per unit body surface area, it increased progressively during long term overeating periods, and decreased markedly during long-term undereating periods. These results suggest that there exists 'Luxuskonsumption', or adaptive diet-induced thermogenesis, during an overeating period and hypometabolism during an undereating period. BMR was affected significantly by the menstrual cycle but not by nutrient composition when daily energy intake was fixed at 2000 kcal for a long time. PMID- 2585155 TI - Does review of peripheral blood smears help in the initial workup of common anemias? AB - Sixty-five physicians were tested to determine the effect of their reviews of red blood cell morphology on their subsequent diagnoses of and workup plans for common anemias. The subjects read clinical and laboratory data for six pairs of cases of anemia, reviewing the blood smear for one case in each pair. They correctly identified the presence or absence of morphologic features on the blood smears 82% of the time. In spite of excellent morphologic discrimination, the number of tests ordered was not affected by blood smear review. In fact, the quality of the physicians' workup plans, measured by numbers of tests appropriately ordered and excluded, was slightly but significantly better when they did not review the smears (p less than 0.005). In addition, smear review did not significantly improve diagnostic accuracy for any of the common anemias studied. Significantly more correct diagnoses were made without smear review for vitamin B12-folate deficiency anemia (p less than 0.015) and thalassemia (p less than 0.0001). Although routine review of blood smears by physicians in the management of common anemias may provide useful information, the authors were unable to demonstrate an improvement in the number or appropriateness of tests ordered or diagnostic accuracy in spite of excellent morphologic discrimination. PMID- 2585156 TI - Clinical scoring system for hypothyroidism: is it useful? AB - A clinical scoring system for hypothyroidism was evaluated against an established "gold standard" (low serum thyroxine and elevated thyroid-stimulating hormone) in 52 adults in a peripheral hospital and in 53 adults in a endocrinology referral clinic. Using a score of 0 as a cutoff point, the scoring system selected patients with hypothyroidism from the referral center for further biochemical evaluation; at the same time, it excluded hypothyroidism with confidence in 42% of euthyroid subjects. In the peripheral hospital, a cutoff score of -10 selected 92% of hypothyroid subjects for further evaluation and excluded hypothyroidism in 55% of euthyroid subjects. Two cutoff points were needed because the prevalences of hypothyroidism in the two centers differed. The simple scoring system increased the pretest probability of disease by 15% in the peripheral hospital and by 19% in the referral clinic. In countries where resources are limited, this scoring system can improve the clinical evaluation of patients who have one or more symptoms of hypothyroidism and reduce the load on referral centers. PMID- 2585157 TI - Pursuit of abnormal coagulation screening tests generates modest hidden preoperative costs. AB - To measure the follow-up costs of preoperative coagulation screening tests, the authors studied 829 consecutive patients undergoing inpatient orthopedic surgery. The results of the initial prothrombin and activated partial thromboplastin time tests were divided into three groups: normal; abnormal above the hospital laboratory's upper limit of normal but below an "action limit"; and abnormal above an action limit. Patients with abnormal preoperative coagulation screening test results were matched on the basis of operative procedure and age with patients who had normal results. The matched groups of patients were compared according to preoperative length of stay and the cost of subsequent related preoperative testing. The average cost of follow-up preoperative testing for patients with abnormal screening test results was $5.05, compared with $0.58 for patients with normal screening results. The difference in average preoperative lengths of stay was not statistically significant. The attributable cost of evaluating an abnormal result added 3% to the cost of the initial coagulation screening program. This represents an average preoperative cost of $0.36 per patient in addition to the cost of the screening tests themselves. PMID- 2585158 TI - Patient perception of involvement in medical care: relationship to illness attitudes and outcomes. AB - OBJECTIVE: The purpose of this study was to explore the relationships among patients' perceptions about the roles they played during medical visits, their subsequent attitudes about their illnesses and treatments, and their self-rated improvement. DESIGN: Questionnaires were completed by patients before, one day after, and one week after their medical visits, and by their physicians following the visits. SETTING: The study was conducted in a general internal medicine faculty practice that provided adult primary care to a largely HMO population. PARTICIPANTS: Adult patients with new or increased symptoms who were capable of reading and understanding the study questionnaire. MAIN RESULTS: Fifty-five patients (47%) reported playing an active role; 62 patients (53%) reported playing a passive role. After adjusting for age, sex, baseline illness ratings, and physician-rated prognosis, "active" patients reported less discomfort (p = 0.04), greater alleviation of symptoms (p = 0.008), and more improvement in their general medical condition (p = 0.04) one week after the visits than did "passive" patients. These differences were not influenced by the roles patients desired to play. Active patients also reported less concern with their illnesses (p = 0.04), a greater sense of control of their illnesses (p = 0.04), and more satisfaction with their physicians (p = 0.02) one day after the visit. Post-visit dysfunction ratings were not related to patients' role perceptions. CONCLUSIONS: Patients' perceptions about their involvement in care appeared to be related to their attitudes about their illnesses as well as to recovery. Further research is needed, however, to determine the factors that influence these role perceptions and to define the types of patients, illnesses, and settings in which the benefits of active-role perceptions are most likely to be realized. PMID- 2585159 TI - Pica: its frequency and significance in patients with iron-deficiency anemia due to chronic gastrointestinal blood loss. AB - PURPOSE: Pica, particularly ice-eating (pagophagia), is a recognized symptom of iron deficiency. The value of pica as a clue to the etiology of blood loss has never been studied. PATIENT POPULATION: Fifty-five unselected patients with iron deficiency anemia due to gastrointestinal blood loss evaluated by a gastroenterology referral service at a city hospital. RESULTS: The patients' mean hematocrit was 26 +/- 15% (SD). Thirty two (58%) had pica, and in 28 (88%) it manifested as pagophagia. Pica was present significantly more often in women (19/32, 68%) than in men (9/23, 39%, p less than 0.05). Pica occurred less frequently in patients with malignancy (2/9 vs. 30/46), but this difference was not significant. CONCLUSION: Pica, a frequent symptom in patients with iron deficiency anemia due to gastrointestinal blood loss, particularly women, is not of value in predicting the cause of bleeding. PMID- 2585161 TI - The road we have taken. PMID- 2585162 TI - General internal medicine: fad or future? PMID- 2585163 TI - ACP guidelines for common diagnostic tests and the practicing internist. PMID- 2585160 TI - Evaluating humanistic attributes of internal medicine residents. AB - OBJECTIVE: Methods of assessing humanism in internal medicine residents have not been completely designed or evaluated. This study used patient satisfaction as a measure of humanism, and assessed the validity of using faculty physicians to evaluate residents' humanistic behavior. Residents' ability to assess themselves was also evaluated. SETTING: A university-affiliated internal medicine training program. SUBJECTS: Forty-seven internal medicine residents were evaluated by patients, faculty, and themselves. DESIGN: Faculty physicians were given standard faculty evaluation and patient satisfaction forms, and were asked to evaluate residents. These evaluations were compared with the patients' responses on the same satisfaction forms. Residents performed self-assessment using identical forms; these responses were compared with those of the faculty and patients. RESULTS: There was no correlation between patients' responses and those of the faculty or residents. There was a significant inverse correlation between resident and faculty responses, especially for the female residents (r = 0.71). CONCLUSION: These findings suggest the need for further study of the evaluation process, including what factors influence individuals to respond as they do. It appears that the use of one rating group is not sufficient to achieve an accurate assessment of residents' humanistic skills. The present status of the process of evaluating humanism is discussed. PMID- 2585164 TI - Guidelines for medical practice: necessary but not sufficient. PMID- 2585165 TI - Blue Cross and Blue Shield Association's perspective on the common diagnostic testing guidelines. PMID- 2585166 TI - Patient-centered research: through the looking glass in search of a paradigm. PMID- 2585167 TI - Advanced achievement in internal medicine: the end of the line for voluntary recertification. PMID- 2585168 TI - Changing of the guard. PMID- 2585170 TI - High-resolution image recovery from image-plane arrays, using convex projections. AB - We consider the problem of reconstructing remotely obtained images from image plane detector arrays. Although the individual detectors may be larger than the blur spot of the imaging optics, high-resolution reconstructions can be obtained by scanning or rotating the image with respect to the detector. As an alternative to matrix inversion or least-squares estimation [Appl. Opt. 26, 3615 (1987)], the method of convex projections is proposed. We show that readily obtained prior knowledge can be used to obtain good-quality imagery with reduced data. The effect of noise on the reconstruction process is considered. PMID- 2585169 TI - Reflections. Until I met Mary. PMID- 2585172 TI - Holographic interferometry applied to the case of large deformations. AB - This investigation in holographic interferometry concerns an approach to a systematic quasi-compensation by appropriate optical modifications at the reconstruction in order that the fringes of interference become visible in the case of large unknown object deformations. The relevant relations are established by using the aberration theory for the image formation in combination with elementary intrinsic differential geometry. PMID- 2585171 TI - Deblurring random time-varying blur. AB - The problem of restoring a constant image distorted by a system of random time varying point-spread functions is studied. The restoration is based on a finite number of images that are observed in a finite period of time. Two features distinguish this problem. The first is that of the signal-noise dependency, and the second is the availability of large amounts of data. The Wiener criterion approach is used to solve the signal-noise-dependency problem. The problem of data size is also alleviated. For the case of time-space separability, a Karhunen Loeve transformation is used to reduce the computations to the size of a single frame problem. For the case in which the noise is stationary in time and in space, a solution based on the direct form of the Wiener filter is presented. The amount of computations here is reduced considerably by the use of fast Fourier transforms and circulant matrix approximations whenever they are valid. PMID- 2585173 TI - Realization of general nondiffracting beams with computer-generated holograms. AB - A new class of solutions to the scalar wave equation was introduced recently that represents transversely localized but totally nondiffracting fields. We show by the method of stationary phase that any of these wave fields can be realized approximately with a laser and a single computer-generated hologram. We briefly discuss various techniques for coding and fabrication of the required hologram and the associated diffraction efficiencies. Using both binary-amplitude and four level phase holograms, we demonstrate experimentally the formation of arbitrary order Bessel beams and rotationally nonsymmetric beams. PMID- 2585174 TI - Constraints on passive spatial coherence filtering of imaging systems due to properties of the impulse response. AB - Properties of the amplitude and intensity impulse responses of passive optical imaging systems have consequences for the spatial coherence filtering properties of such systems. It is shown that imaging systems that have both space-invariant impulse responses and truncating pupil functions have no capability to block spatially coherent sources while imaging those that are incoherent. However, examples of systems with space-variant impulse responses with approximately such capabilities appear to be realizable for a certain range of parameters. However, even space-variant systems cannot block unresolved coherent sources while retaining the capability of imaging those that are spacially incoherent for the same range of source-plane coordinates. PMID- 2585175 TI - Opponent-color receptive-field profiles determined from large-area psychophysical measurements. AB - By compensating for retinal inhomogeneity and using the opponent-color characteristics of retinal receptive fields, some of the problems associated with previous methods of inferring local spatial-processing properties from sine-wave contrast-sensitivity measurements can be eliminated. Forced-choice contrast detection thresholds were obtained for circular frequency-modulated patterns, over a wide range of spatial and temporal frequencies, with three subjects. Eye movement artifacts were minimized by image stabilization. The luminance contrast sensitivity (L) for a given isochromatic stimulus and the chromatic contrast sensitivity (C) for the corresponding isoluminance stimulus were measured in rapid succession, under identical conditions, using red and green components with accurately known spectral distributions. Receptive-field center (E) and surround (I) frequency functions were then calculated from the L and C data by solving two linear equations in two unknowns, with coefficients given by the spectral characteristics of the stimuli and the long-wave and middle-wave cone pigments. The results depend on the small differences of large numbers inherent in opponent color responses, so they are somewhat noisy, but the forms of these (E-I) spatial profiles are similar to those obtained by other methods. PMID- 2585176 TI - Maintaining the unity of oral and maxillofacial surgery. PMID- 2585177 TI - Maxillomandibular advancement surgery in 23 patients with obstructive sleep apnea syndrome. AB - Twenty-three patients with obstructive sleep apnea syndrome (OSAS) documented by polysomnography underwent maxillomandibular advancement via Le Fort I, and sagittal ramus split osteotomies followed by rigid fixation with miniplates and bicortical screws. Partial turbinectomies and septal reconstruction were simultaneously performed. Pre- and post-operative cephalometric radiographs were analyzed by computer. Hyoid position and posterior airway space changes did not correlate with clinical success. The surgical success (respiratory disturbance index less than 10) with maxillomandibular advancement was 65%. The total desaturations below 90% greatly decreased. Ninety-six percent of patients were subjectively and objectively improved. PMID- 2585178 TI - Arthroscopic TMJ surgery: effects on signs, symptoms, and disc position. AB - Nineteen subjects with documented intra-articular pathology refractory to nonsurgical therapies underwent temporomandibular joint (TMJ) arthroscopy involving lysis and lavage in the superior joint space. Following surgery, subjects were evaluated for 6 to 12 months by clinical examinations and questionnaires at designated time periods and by postsurgical joint imaging. Significant improvement was noted in pain, mandibular movement, and diet. No improvement was noted in the incidence of joint sounds, and disc position was unchanged in 80% of the joints. The findings suggest that disc repositioning may not be needed to achieve clinical success. PMID- 2585179 TI - Reconstruction of frontal and frontal-nasal deformities with prefabricated custom implants. AB - The use of prefabricated custom silicone rubber implants for frontal and nasofrontal deformities produces predictable esthetic results with minimal operative and postoperative morbidity and/or complications in selected patients. Over the past 8 years, 15 custom silicone rubber implants have been placed with good to excellent results. Only one implant was removed due to postoperative infection. This implant was successfully replaced upon resolution of the infection. PMID- 2585180 TI - Temporary silastic implantation following discectomy in the primate temporomandibular joint. AB - Silastic (Dow Corning, Midland, MI) has been used in the surgical treatment of a variety of temporomandibular joint (TMJ) disorders as either a permanent or temporary implant. In this study four Macaca fascicularis monkeys underwent bilateral TMJ discectomies and high condylar shaves. The experimental side was treated with a Silastic sheet implant which was removed at 3 months postdiscectomy. The contralateral side was left without an implant and served as a control. Animals were killed at 3, 4, 5, and 6 months postoperatively. A fibrous connective tissue capsule was found around the Silastic implant at all time intervals. This capsule formed a single joint space between the inferior surface of the glenoid fossa and articulating surface of the condyle. Three months following implant removal, the capsule was still present and there was no significant inflammatory cell infiltrate. The severity of the degenerative changes was decreased on the implant side. PMID- 2585182 TI - Non-Hodgkin's lymphoma of the buccal gingiva as the initial manifestation of AIDS. PMID- 2585181 TI - Effect of stretching on the physical properties of stainless steel wire. AB - Stretching of 25-gauge stainless steel wire causes alterations in the physical properties of the wire. The yield strength and ultimate tensile strength are increased and the elasticity is decreased. These alterations make stretched wire more satisfactory for maxillofacial surgical applications than unstretched wire. PMID- 2585183 TI - Metastatic thyroid carcinoma of the mandible: case report. PMID- 2585184 TI - Arteriovenous malformation of the mandible: survey of previously unreported cases and case report. PMID- 2585185 TI - False aneurysm of the facial artery. AB - A case of an unusual traumatic aneurysm of the facial artery secondary to blunt trauma is reported. The lesion was typical in that it was pulsatile, had a systolic bruit, and had a filling defect that was evident on carotid angiography. Although a traumatic aneurysm is a rare occurrence in the facial region, the inclusion of this lesion in the differential diagnosis of soft tissue lesions is important if the serious consequences of hemorrhage are to be avoided. PMID- 2585186 TI - Recurrent dislocation of the mandible in a patient with myotonic dystrophy. PMID- 2585187 TI - Reflex sympathetic dystrophy linked to venipuncture: a case report. AB - A case of reflex sympathetic dystrophy following routine venipuncture is presented. This syndrome is characterized by pain, stiffness, and dysfunction of an extremity in response to a minor injury, and may lead to loss of the involved limb. The syndrome is poorly understood and often misdiagnosed. Early recognition and intensive physical therapy are most important in treating this disorder. PMID- 2585188 TI - An aid to nasal tracheal intubation. PMID- 2585189 TI - A uniform recording method for surgical workup on study models. PMID- 2585190 TI - TMJ articular disc perforation--a new perspective. PMID- 2585191 TI - Seeing a different future. PMID- 2585192 TI - Casting the second stone. PMID- 2585193 TI - [The role of high-resolution CT in evaluating disease of the posterior tympanum]. AB - The posterior tympanum consists of several irregular eminences, ridges, and sinuses. These sinuses do not communicate with the mastoid air cell system, and cholesteatoma and/or granulation tissue prefer to fill them. This area cannot be visualized with ease by the usual surgical approach, and is thus quite important for surgeons. Recent developments in high-resolution computed tomography (HRCT) allow more than ever precise identification of subtle changes in the posterior tympanum. Axial HRCT sections provide essential information for the preoperative evaluation of the posterior tympanum. The performance of surgeons has been promoted both in evaluation and treatment planning of patient with suspected posterior tympanic lesions. HRCT findings were compared with the operative findings in 52 patients (54 ears) who had the operation for chronic otitis media. Important findings by HRCT diagnosis of posterior tympanum are as follows: (1) Bone destruction in the posterosuperior part of the tympanic anulus and in the lateral wall of the facial sinus are the important findings for the diagnosis of invasion of cholesteatoma in the posterior tympanum. (2) Similarly important finding is the bone destruction of the pyramidal eminence. This was found in 6 of 9 cases with cholesteatomas extending into the sinus tympani. (3) The soft tissue density in the posterior tympanum does not necessarily indicate pathological processes. Effusion in the posterior tympanum is imaged as soft tissue density, and can not be differentiated from cholesteatoma or granulation by present HRCT. PMID- 2585194 TI - [Histochemical study of acetylcholine receptors at the neuromuscular junctions of the cat posterior cricoarytenoid muscle using erabutoxin B]. AB - Acetylcholine receptors (AchRs) at the neuromuscular junctions of the cat posterior cricoarytenoid muscle (PCA muscle) were demonstrated by using erabutoxin b (Eb) which has a curare-like action. Eb is one of the short-chain neurotoxins which is obtained from Laticauda-semifasciata. At the light microscopic level, the localization of the neuromuscular junctions was detected on the muscle fiber by rhodamine-labeled Eb (TMR-Eb) under a fluorescein microscopy. For the electron microscopy horseradish peroxidase-labeled Eb (HRP Eb) was used. After incubation with HRP-Eb conjugate the tissue was fixed in a mixture of paraformaldehyde and glutaraldehyde, then embedded in Epon. The reaction products were largely restricted to the postsynaptic membrane at the neuromuscular junction. Acetylcholinesterase (AchE) activity was also demonstrated electron microscopically by Karnovsky's and Lewis' methods respectively. The reaction products were localized at the subneural apparatus of the neuromuscular junction. Both these results were compared. PMID- 2585195 TI - [Four cases of dysosmia with no vocal cords adduction during sniff (laryngeal dysosmia)]. AB - The author first reported that the vocal cords adduct during sniff. This movement was observed both in normal and in anosmic subjects. In this paper four cases of dysosmia with no adduction of vocal cords during sniff was reported. The pattern of their olfactometry showed same tendencies, normal detective thresholds and inability of recognition and/or very low recognition threshold. With the observations and referenced articles, the author concluded that the vocal cord's adduction during sniff is a specific movement when the larynx concern with olfaction, and that the adductory movements is related to olfactory recognition. It was thought that the orbital cortex integrates the afferent stimulations from the larynx during sniff and olfaction from the nose. The author concluded also there exists these reported kind of dysosmia with no vocal cord adductory movement. PMID- 2585196 TI - [Sympathetic innervation in the larynx of cats]. AB - The site of origins, peripheral courses and intramucosal distribution of the sympathetic post-ganglionic nerve fibers supplying to the larynx were investigated by means of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and Falck-Hillarp method in 51 cats. The cervical sympathetic ganglia which send the postganglionic fibers to the larynx were the superior cervical ganglion (SCG), middle cervical ganglion (MCG), and stellate ganglion (SG). Location of MCG was at the bifurcation of the cervical sympathetic trunk, rostrally to the point of its crossing with the subclavian artery. After WGA-HRP injection, labeled sympathetic nerve fibers were observed mainly in the wall of the blood vessels and around the laryngeal glands of the posterior and caudal parts of the larynx. Labeled fibers originated from SCG were seen in the mucosa of the arytenoid region and posterior glottis ipsilaterally. Both the internal and external branches of the superior and inferior laryngeal nerves contained the postganglionic fibers from SCG. Labeled nerve fibers from MCG were recognized in the ipsilateral mucosa of the glottis and subglottis and were also contained in the internal and external branches of the superior and the inferior laryngeal nerves. Labeled sympathetic nerve fibers from SG appeared in the mucosa caudal to the first tracheal ring. The pattern of distribution of labeled sympathetic nerve fibers revealed by WGA-HRP technique coincided with that of the noradrenergic fibers stained by Falck-Hillarp method. PMID- 2585197 TI - [Surgical treatment of subglottic stenosis in children--laryngotracheal plastic surgery with autogenous costal cartilage graft]. AB - We performed laryngotracheal plastic surgery by transplantation of autogenous costal cartilage graft in 9 cases of subglottic stenosis (2 with congenital type and 7 with acquired type). Of 9 cases, 3 cases had the lesion after long-term intubation, 2 cases after tracheotomy and 2 cases after laryngo-tracheo bronchitis. Five cases aged one year and the remaining 4 cases 2 years, 3 years, 4 years and 6 years old, respectively. We could successfully decannulate in all the 9 cases after our plastic surgery. The period from surgical treatment to decannulation varied from 9 days to 6 months. However, 8 cases were decannulated in 2 months after surgery. Cotton et al (1978) did not use any stents in their treatment for subglottic stenosis, but we did in all of our cases. We preferred stents of the silicone Y-tube, and the recommendable duration of cannulation is 4 weeks. PMID- 2585198 TI - [Stereoendoscopic observation of the larynx--vocal fold length in respiration and in phonation with vocal pitch change]. AB - By use of a rigid stereoendoscope system, the vocal fold length in living human subjects was measured in absolute values. The subjects were seven adults. None of them had special training for singing. The measurements were made during inspiration and phonation with systematic changes in vocal pitch. During respiration, the glottal width was widened in inspiration and narrowed in expiration. Following the widening of the glottis, the vocal fold length increased and following the narrowing of the glottis, it decreased. In steady phonation with systematic changes in vocal pitch, the minimum length of the vocal fold ranged from 5.6 to 9.8mm in males and from 6.0 to 7.3mm in females. The range of maximum length was from 10.7 to 15.0mm in males and from 9.2 to 12.6mm in females. In male subjects, the vocal fold length in usual spoken pitch (USP) ranged from 8.9 to 11.3mm. In the female subjects, it ranged from 7.0 to 10.1mm. It is noted that the subjects having a larger value of the vocal fold length in USP, also have larger value in the minimum and maximum length of the vocal fold. There was a general tendency for vocal fold length to increase with pitch ascent at least within some portion of the voice range of spoken voice. The rate of the elongation in relation to the pitch ascent appears to be variable among the subjects. It is also noted that the vocal fold length does not necessarily increase with the increase in vocal pitch in the higher portion of the voice range, including both natural and falsetto registers. In these pitch ranges, the physiological mechanisms for pitch control might not consistently be seen in the change of the vocal fold length. It seems that these variabilities of relation between the vocal pitch and the vocal fold length are evident in spoken voice, while uniform patterns are dominantly seen in singing voice, although further research is needed to support this notion. PMID- 2585199 TI - [Modification of speech encoding process of single channel cochlear implant utilizing digital delay circuit]. AB - Speech perception by single channel cochlear implant can be improved to some extent by modifying the encoding process of the speech signals. The principle of our encoding strategy is to present speech signals with appropriate delay time for lower frequency components of the speech sound, while without delay for higher frequency components. This is based on a cochlear physiology that higher frequency sounds are perceived earlier than lower frequency sounds, since the former is perceived at the basal turn and the latter at the apical turn. The following tests were performed without the aid of lip reading in the two patients implanted with a single channel cochlear implant of 3M-House design. Lower frequency components of the speech signals were digitally delayed with a Sony SDP 777 ES surround processor. The results indicated that the optimal delay time for identification of /i/, /e/ and /u/ needed longer delay time, while that of /a/ and /o/ need shorter delay time, corresponding to the difference between the first and second formant of each vowel. Comparison of vowel perception with and without delay coding showed that vowel identification with delay coding was superior to that without it; 30% vs. 16% in case 1, and 48% vs. 30% in case 2. PMID- 2585200 TI - [Nasal resistance in facial palsy]. AB - The parasympathetic nerve which innervates the nasal mucosa is known to take a course along the facial nerve, geniculate ganglion, greater petrosal nerve and Vidian nerve as a preganglionic component. In the case of facial palsy with decreased lacrimation, it is proposed that the patients have a damage of the geniculate or suprageniculate lesion. This lesion is thought to cause parasympathetic, preganglionic denervation to the nasal mucosa. In the case of facial palsy with decreased lacrimation in Schirmer's test, it can be considered that the preganglionic nerve fibers of their parasympathetic nerves to the nose were injured. Twenty-seven cases of facial palsy were selected for this study. We found that 18 (66.7%) out of 27 patients with facial palsy showed a nasal cycle and that 9 (33.3%) showed no nasal cycle. Ten (62.5%) out of 16 patients with decreased lacrimation showed a nasal cycle. In Hasegawa and Kern's study, a nasal cycle was present in 72% of 50 normal subjects. Our data was similar to their finding. Therefore we conclude that the nasal cycle was not influenced by injury to the preganglionic, parasympathetic nerve to the nose. PMID- 2585201 TI - [Clinical evaluation of local administration of RIL-2 in head and neck cancer]. AB - Recombinant Interleukin-2 (rIL-2) was administered locally to 20 patients with head and neck cancer. 800 thousand units of TGP-3 were injected around the tumor mass every day for about 4 weeks. Complete response (CR) was obtained in two cases with lip cancer and one with lingual cancer showed partial response (PR), and minor response (MR) in oral floor cancer. No recurrence of tumors was observed in the two cases of lip cancer. Chemotherapy was performed with rIL-2 in cases responding only insufficiently to rIL-2. It was interesting that arterial infusion of anticancer drugs subsequent to local administration of rIL-2 resulted in a dramatic decrease in tumor size in a short time. It is suggested that local administration of rIL-2 may play an important role in multimodal treatment for head and neck cancer. PMID- 2585202 TI - [Nasal allergy and leukotriene. 2. Kinetics of peptide leukotrienes and inflammatory cells in nasal lavage fluid after antigen challenge]. AB - The purpose of this study is to clarify the role of peptide leukotrienes (LTs) on the onset of characteristic hyperreactive nasal symptoms of nasal allergy by observing the time course of the correlation among degrees of nasal symptoms, and by observing the amount of chemical mediators and the number of inflammatory cells in the nasal lavage fluid after nasal antigen challenge in subjects with Japanese cedar pollinosis during off season. Sneezing was terminated within 10 minutes and nasal discharge within 2 hours. However, time course change of the percent increase of nasal airway resistance showed dual response consisting of immediate and late phase responses. The peak of the former was seen at 30 minutes and the latter was at 7 hours after provocation. The significant increase of eosinophils in the nasal lavage fluid was observed during both the immediate and the late phase responses, but during the late phase response, the increase was more prominent. Basophilic cells definitely increased during the late phase response. The amount of LTs in the nasal lavage fluid increased significantly during both the immediate and the late phase responses. In contrast, the level of histamine increased significantly only during the immediate phase response. Considering that LTs, especially LTD4, has potent and persistent effect on causing swelling of nasal mucosa, LTs may play important role in causing nasal obstruction during both the immediate and the late phase responses after antigen challenge. On the other hand, the role of histamine may be confined to cause the hyperreactive nasal symptoms during the immediate phase response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585203 TI - [Influence of otitis media with effusion on perilymph and round window membrane]. AB - To investigate the influence of middle ear effusion (MEE) on perilymph (PL) and the round window membrane (RWM), an experimental otitis media with effusion (OME) was manufactured in chinchillas by injecting the tympanic cavity with immune complexes. The presence of MEE lasted 9 days after the injection of immune complexes. Perilymph was aspirated on the fourth, tenth, 21st, and 60th days after the inoculation. The mean concentrations of albumin, IgG, histamine, and prostaglandin E2 (PGE2) were significantly greater in PL obtained from OME induced ears than in those from normal control ears. The 3H-PGE2 placed on the RWM of pathologically affected ears passed into PL in significantly greater amounts, compared to normal control ears. The findings of the present study indicate that MEE affect the biochemical milieu of PL. PMID- 2585204 TI - [Ossicular vibration in human temporal bones]. AB - Vibration mode of the ossicles was investigated in twelve fresh human temporal bones using a video measuring system (VMS, Technical Instrument). This system allows one to observe the ossicular vibration and to measure its vibration amplitude (up to 0.2 micron) and phase angle. In this study the inner and middle ear was kept intact except for two small holes in the tympanic tegmen. These holes were for the observation of ossicular movement and were covered with a thin cover glass during the experiment. The vibration amplitude and phase angle of the umbo, malleus head, lenticular process and stapes head were measured at 19 frequencies between 0.1 kHz and 4.5 kHz. The umbo moved piston-like at 0.1-0.8 kHz and 2.6-4.5 kHz but in an ellipse at 1.0-2.4 kHz. The malleus head showed elliptical movement with its long axis anteriorly tilted around 45 degrees from the direction of the umbo vibration at 0.1 kHz. Both the lenticular process and stapes head showed similar movement; piston-like in lower frequencies and elliptical in higher frequencies. The umbo, lenticular process and stapes head vibrated parallel at lower frequencies. The position, displacement and phase angle of the rotation axis of the ossicles was calculated based on the displacement and phase angle of the umbo, malleus head and lenticular process. The axis was around the level of the neck of the malleus in frequencies lower than the resonant frequency, beneath the level of the short process near the resonant frequency and at the top of the malleus head in higher frequencies. The average axis displacement was 0.9 microns at 1 kHz but much smaller at frequencies lower than 0.8 kHz or higher than 2 kHz. This suggests that such axis movement may reduce the efficiency of the middle ear sound transmission. PMID- 2585205 TI - [The clinical study of functional deafness]. AB - Ninety eight cases with functional deaf who visited in recent 13 years were studied. The results were as follows; 1) Patients were likely to increase in the last 10 years. 2) Females seemed to be more frequently suffered from functional deafness rather than males. 3) It was found that there were two peaks of age when patient had functional deafness. 4) Chief complaints in most cases were hearing loss. 5) Pure tone audiograms in these cases showed bilateral in most cases, symmetrical curve, sensorineural in type, flat and sloping in shape (including saucer type), and its hearing level revealed in 30-40dB in most cases. 6) Bekesy audiometry was useful for diagnosis. Ninety cases out of 98 showed the V type of Jerger classification. 7) Psychological problems related to troubles of school and friends were observed as causative factors, and episodes concerned otological problems were found to be as triggers. 8) It is possible to make sure a diagnosis by using ABR. For diagnosis, however, it was necessary to doubt the presence of this disease, and then it was important to find out the discrepancy in a battery of hearing test. 9) In some cases, the exactly the same, but higher threshold levels for hearing are always detected in repeated examinations of their audiograms, suggesting the actual disturbance of the loudness recognition in these patients. PMID- 2585206 TI - [Acute low tone sensorineural hearing loss caused by inner ear barotrauma]. AB - Three cases of inner ear barotrauma with subjective symptoms and hearing impairment which were similar to the low tone sudden deafness were reported. Case 1 was a 34-year-old man who developed a hearing loss in the next morning of taking an airplane and recovered four days after. Case 2 was a 42-year-old man who developed a hearing loss 2 days after flying in an airplane and hearing loss have recurred 4 times in his right ear for 3 months. Eight months after recovery of previous recurrent attack, a hearing loss occurred in his left ear without flying and recurred twice for 3 weeks. Case 3 was a 25-year-old woman who developed a hearing loss in the right ear after 24 meter depth scuba diving and recurred 4 times for 40 days. Those three patients complained of no vertigo at any attacks and were treated conservatively. From previous reports and the onset and the course of hearing disturbance, acute low tone sensorineural hearing loss in case 1 and case 2 was thought to be caused by circulatory disturbance of the inner ear and in case 3 thought to be caused by inner ear window rupture. But, endolymphatic hydrops was also needed to be take into account in those three cases as a common possible cause. Inner ear barotrauma and so called labyrinthine window rupture were considered to be one of the diseases needed to differentiate from low tone sudden deafness without reference to mono-attack type or recurrent type. PMID- 2585207 TI - [Contralateral hearing and tympanoplasty]. AB - The relationship between the contralateral hearing threshold in the operated ear and the type of tympanoplasty and the hearing threshold in the operated ear was investigated in this report. The subjects of analysis were 863 ears that received tympanoplasty during the past nine years at the Nippon Medical School Main Hospital. Patients who had good hearing in the contralateral ear received type I tympanoplasty more frequently than did those who had poor hearing on the contralateral ear. On the other hand, patients who had poor hearing in the contralateral ear received a modified type III tympanoplasty more frequently. Patients who had good hearing in the contralateral ear tended to have better hearing in the operated ear compared to those who had poor hearing in the contralateral ear. The hearing threshold in patients who had normal contralateral hearing on the average had 20 dB better hearing than did those who had profound hearing loss in the contralateral ear. More than one third of the patients whose hearing thresholds were worse than 30 dB in the operated ear also had a contralateral hearing loss of 30 dB or more. The decision to perform tympanoplasty in cases of the better hearing ear or the only hearing ear must be made very carefully. The contralateral hearing in patients with chronic otitis media, however, is frequently not normal as was evidenced in this investigation. Also, patients who had poor hearing or were deaf in the contralateral ear received more benefit by tympanoplasty than did those who had good hearing in the contralateral ear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585208 TI - [A case of congenital laryngeal web with subglottic stenosis]. AB - A severe case of congenital laryngeal web with subglottic stenosis was reported. The patient had weak crying after birth and stridor was noticed from one month old. He had tracheostomy at two month old and the incision of the web was attempted under laryngomicrosurgery with CO2 LASER, although the attempt failed due to combined subglottic stenosis. The "trough method" was applied at the age of one year. The web was incised and subglottic granulation including the excessive cartilaginous tissue was removed through a laryngotracheal fissure. A piece of silicone membrane was inserted between the vocal cords preventing from adhesion and a silicone tube stent was also inserted into the subglottic space and trachea to keep the laryngotracheal space open widely. After one month and a half, the silicon membrane and silicon tube were removed and a silicon T-tube was inserted instead of the silicon tube. The anterior wall of the laryngotracheal space was closed using a hinge flap. The patient can vocalize and does not complain of dyspnea at present, one year after the removal of the T-tube. PMID- 2585209 TI - [A study on the effect of infrasound]. AB - In order to examine the influence of infrasound that is becoming topical in society, human beings and guinea pigs were exposed to infrasound. After exposure, the hearing level, vestibular functions and autonomic nervous functions of human beings were examined, and endocochlear potential (EP) and cochlear microphonics (CM) of guinea pigs were examined. Next, after guinea pigs were exposed to intense audible low frequency sound that was born secondarily from infrasound and/or vibration of whole body concerning about air pressure change of infrasound, their EP and CM were examined. The results obtained were as follows: 1) By exposure of infrasound 10-15Ha 130-135dB LSPL for 30min. to human beings, their hearing level, vestibular functions and autonomic nervous functions were not changed. 2) After exposure of infrasound 15Hz 135-140dB LSPL for 24hrs. 72hrs. to guinea pigs, their EP and CM remained normal. 3) After each exposure of audible low frequency sound 90Hz 120dB SPL for 72hrs., 150Hz 110dB SPL for 72hrs. and 200Hz 100dB SPL for 72hrs. to guinea pigs, their EP became abnormal though their CM remained normal. 4) After exposure of 15Hz 500 mu +/- 30 mu vibration for 72hrs. to guinea pigs, both EP and CM remained normal. 5) After exposure of both audible low frequency sound 150Hz 100dB SPL and vibration 15Hz 500 mu +/- 30 mu for 72hrs. to guinea pigs, their EP became abnormal though their CM remained normal. PMID- 2585210 TI - [Aging and reference values of the parameters in optokinetic nystagmus]. AB - Changes in optokinetic nystagmus by age were assessed, and preparation of reference values by age was made by the use of the data from 834 reference subjects. As a result, changes by age were observed at the test on optokinetic nystagmus. The reference values by these changes can be approximated with the quadratic and was considered, therefore, to be useful clinically. Four parameters were set for the test items for optokinetic nystagmus as the total number of nystagmus (NYS); the mean of eye velocity during the fast phase of nystagmus (FM); the algebraic summations of eye velocity (VEL) and amplitude (AMP) during the slow phase of nystagmus. As the process for statistical analysis, variables were divided into 7 groups, and after removing outlier (any extraneous data) in each group, changes in variables by age were assessed by the one-way analysis of variance and the method of multiple comparison (Ryan's method). As a result: 1) the age group of each variable seemed to develop into normal distribution; 2) it was presumed that change in NYS by age is less; 3-1) regarding FM, VEL and AMP, no change was observed in the variable by ages on 30s and 40s; and 3-2) however, decrease in the measured value was observed in ages on 60s along with aging. From these, the ages on 50s are the generation when the measured values of optokinetic nystagmus change. On the other hand, the reference values calculated, taking age into consideration, could be approximated with the quadratic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585212 TI - [Early hearing screening for brain impairment baby--Crib-O-Gram]. AB - A retrospective investigation by ABR and COG was performed to children with brain impairment determined by neurological follow-up out of children who had hearing screening test, and the relationship with the presence or not of hearing loss was analyzed. The results obtained are as follows. 1) The failure rate in COG test was 46.3% in the brain impairment group. It was significantly higher than in the hearing loss high-risk group and the low-risk group. However, 20% of 101 children with brain impairment ware cases in which the COG test could not be performed. Presumably , this is due to the special character of COG test. 2) In the brain impairment children group, the rate of true positive, true negative and false negative by COG as to the presence or not of hearing loss stood at 68.8%, 31.3%, and 0% respectively. Since, however, 32.4% of the children who failed to pass COG had hearing loss, the usefulness of COG can be said to be high. 3) The incidence of hearing loss was significantly high at 15.0% in the brain impairment group compared with other groups. In contrast, the rate of true positive was significantly high, the rate of true negative significantly low and no false negative was noted in the low-risk group. So COG was considered appropriate as a hearing screening device that can be used from the neonatal period. 4) In the brain impairment group, the rate of true positive by ABR was high at 86.7%, but the rate of true negative was 13%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585211 TI - [Animal model of motion sickness in rats]. AB - Complex accelerative stimuli can induce pica in rats as well as the treatment with poisons, which means eating of non-nutritive substances such as kaolin, in proportion to the severity of their sickness. For the purpose of using pica as an index of motion sickness in rats, we examined what kind of rotation was effective for inducing pica in rats with or without normal bilateral labyrinth functions. Clinically potent anti-motion sickness drugs, such as scopolamine, methamphetamine, diphenhydramine, were examined in reducing rotation-induced pica in rats. Rats ate more kaolin after double rotation with continuously changing acceleration, than after single rotation. Both the animals treated with anti motion sickness drugs or labyrinthectomy ate less kaolin even after double rotation. Since the physiological and pharmacological mechanisms for inducing pica in rats were similar with those of motion sickness in humans, pica in rats should be an acceptable index of their motion sickness. In order to study neural mechanisms of motion sickness in rats, we examined the effects of an anti cholinergic as a potent anti-motion sickness drug and cholinergics as an antagonistic drug treated during the 4th-7th day of rotation on both habituation to double rotation within daily rotations for 10-11 days, using pica as an index of motion sickness. Rats were separated into three groups according to their initial susceptibility, and rats with low susceptibility were omitted in these experiments. Scopolamine (TTS-scopolamine) as an anticholinergic facilitated habituation to motion, especially in rats with moderate susceptibility. Treatment of physostigmine suppressed residual habituation to motion sickness in rats, especially with moderate susceptibility, though neostigmine, peripherally acting anti-cholinesterase, had no effect. These results suggested that centrally acting acetylcholine play an important role in suppressing habituation of motion sickness. In conclusion, rats should be a convenient model for studying for motion sickness, as we examined one of the neural mechanisms in motion sickness using pica as an index. PMID- 2585213 TI - Effects of race on the validity of clinical estimates of gestational age. PMID- 2585214 TI - Absence of tolerance to the behavioral effects of methylphenidate in hyperactive and inattentive children. AB - To determine whether the behavioral benefits of methylphenidate in hyperactive and inattentive children decline during long-term treatment, we analyzed data from 108 hyperactive students who responded well to methylphenidate therapy for 3 to 10 years. Responders were identified by their consistent improvement from baseline on standard teacher rating scales. The therapeutically effective drug doses were corrected for body size and evaluated in relation to increasing age and treatment duration. Body size corrections included milligrams per kilogram, milligrams per kilogram to the 0.7th power, and milligrams per square meter of estimated body surface area. The major findings were that (1) the dose of methylphenidate, when adjusted for growth, did not change significantly during the 3 to 10 years of treatment; (2) the loss of a previously satisfactory response to methylphenidate treatment was uncommon (6%) and when present was related to middle school enrollment, male gender, noncompliance with medication, and lower than customary dosage; (3) the dose calculations that minimized the effects of growth with age were milligrams per kilogram to the 0.7th power and milligrams per square meter of estimated body surface area; and (4) the commonly used milligrams per kilogram dose consistently overcorrected for growth with advancing age. PMID- 2585215 TI - Maternal-fetal transport of vitamin K1 and its effects on coagulation in premature infants. AB - We conducted a prospective study to determine (1) the maternal-fetal vitamin K1 transport in premature infants after vitamin K1 was given to the mothers antenatally and (2) the vitamin K1 effects on blood coagulation in the babies. Women in labor at less than or equal to 34 weeks of gestation were randomly selected to receive antenatal vitamin K1, 5 mg given intramuscularly (vitamin K1 group), or no vitamin K1 (control group). Eight infants, including one set of twins, were in the vitamin K1 group and six in the control group. Vitamin K1 concentrations were higher in the vitamin K1 group than in the control group (p = 0.06). Activated partial thromboplastin time was prolonged, and factor II coagulation activity and factor II antigen were proportionately decreased in cord plasma in both groups. The average ratio of factor II coagulation activity to antigen was not decreased in either group. Protein induced by vitamin K absence II (PIVKA-II) was not detectable in any cord plasma sample in either group. These findings support previous reports that the decreased vitamin K-dependent coagulation activity in premature infants is the result of reduced synthesis of precursor proteins, rather than the result of vitamin K deficiency, and suggest that additional vitamin K1 is not likely to improve coagulation activity. Among those infants who underwent cranial ultrasonography, all four in the vitamin K1 group and one of five in the control group had mild intraventricular hemorrhage. Studies of a larger number of patients are necessary before it can be established that maternal antenatal administration of vitamin K1 results in improvement of coagulation and the prevention of intraventricular hemorrhage in premature infants. PMID- 2585216 TI - Use of continuous caudal block to relieve lower-extremity ischemia caused by vasculitis in a child with meningococcemia. PMID- 2585217 TI - Neonatal screening for congenital adrenal hyperplasia. PMID- 2585218 TI - Incidence of natal and neonatal teeth. PMID- 2585219 TI - Toxicity of tea containing pyrrolizidine alkaloids. PMID- 2585220 TI - Vitamin K deficiency in breast-fed infants. PMID- 2585221 TI - Megalencephaly in thanatophoric dysplasia and in achondroplasia. PMID- 2585222 TI - Management of Stevens-Johnson syndrome and toxic epidermal necrolysis in children. AB - A retrospective analysis of 21 consecutive patients hospitalized with either Stevens-Johnson syndrome or toxic epidermal necrolysis was carried out to assess morbidity and mortality rates and to establish the value of a specific management practice. Fourteen children with Stevens-Johnson syndrome and seven with toxic epidermal necrolysis were cared for at the Children's Memorial Hospital, Chicago, between 1978 and 1988. All were managed in a well-staffed medical ward or, when necessary, in the pediatric intensive care unit. Supportive measures included reverse barrier isolation, intravenous fluids and nutritional support, meticulous skin care, early detection and treatment of infection, and daily ophthalmologic examination. No patient was treated with systemic steroids. The mortality rate was zero. Eye complications, consisting of dry eyes or mild chronic symblepharon, were the most significant long-term sequelae. PMID- 2585223 TI - Temperature response to acetaminophen and risk of occult bacteremia: a case control study. AB - A case-control study of 34 children with occult bacteremia was conducted to test the hypothesis that nonresponse to acetaminophen (decrease less than or equal to 0.8 degrees C) is a risk factor for occult bacteremia. Febrile children visiting the emergency center from May 1986 to October 1987 were monitored for occult bacteremia. Inclusion criteria were age 2 months to 6 years, temperature greater than or equal to 38.9 degrees C, and having a blood culture. Exclusion criteria were serious acute or chronic illness, sponging for fever reduction, current therapy with antibiotics or steroids, and admission to the hospital. Records of 3892 febrile children were reviewed. Of these, 2101 (54%) had a blood culture and 1028 (26%) were eligible. All patients (positive blood culture) were matched with two control subjects (negative blood culture). Patients and control subjects had similar age, gender, ethnicity, height of initial temperature, time to second temperature, and dose of acetaminophen. The estimated risk of occult bacteremia for nonresponders was 9.2 (95% confidence interval 2.7, 32.0). We conclude that children who do not respond to acetaminophen by at least a 0.8 degrees C decrease in temperature have an increased risk of occult bacteremia. However, achieving a response to acetaminophen does not eliminate the possibility that the child has occult bacteremia. PMID- 2585224 TI - Sleep-associated breathing disorders in morbidly obese children and adolescents. AB - Forty-one children and adolescents with a history of breathing difficulty during sleep and morbid obesity, defined as greater than 150% ideal body weight, underwent polysomnography to determine the incidence of sleep-associated breathing disorders. Seventeen patients also performed pulmonary function testing. The mean patient age was 10.3 +/- 4.4 (SD) years, and mean percent of ideal body weight was 208 +/- 42.2. A sleep history questionnaire showed that all patients snored, but frank apnea was reported in only 32%. The pulmonary function tests showed 18% (3/17) with a restrictive defect and 47% (8/17) with obstructive changes. The polysomnograms in 37% (15/41) of the patients were abnormal because of apnea, hypopnea, excessive arousals, or abnormalities in gas exchange. Multiple regression analysis demonstrated no significant association between weight, age, or gender and any physiologic measure on the polysomnogram. Most of the abnormal polysomnograms (13/15) were mildly abnormal, but two showed sufficiently severe abnormalities to require clinical intervention. We conclude that children and adolescents with morbid obesity are at risk for sleep associated breathing disorders; their polysomnographic abnormalities are usually mild but rarely may be severe enough to require clinical intervention. PMID- 2585225 TI - Abnormal control of ventilation in adolescents with myelodysplasia. AB - Infants with myelomeningocele have abnormalities in ventilatory control. To determine whether these persist into later life, we studied 14 patients with myelomeningocele and Arnold-Chiari malformation (age 18.0 +/- 0.8 (SE) years), and compared them with 14 control subjects (age 24.0 +/- 0.9 years). Pulmonary function and ventilatory muscle strength did not differ between patients with myelomeningocele and control subjects. Hypercapnic ventilatory responses were significantly lower in the group with myelomeningocele (1.98 L/min/mm Hg) compared with control values (3.33 L/min/mm Hg; p less than 0.01). Hypoxic ventilatory responses (-1.4 L/min/%oxygen saturation of hemoglobin in arterial blood) were not significantly different from control values (-2.14 L/min/%oxygen saturation). In control subjects the hypercapnic and hypoxic ventilatory responses were highly correlated with each other within subjects (r = 0.84; p less than 0.002) but not in those with myelomeningocele (r = 0.34; not significant). We concluded that adolescents and young adults with myelomeningocele have abnormalities in control of ventilation during sleep and wakefulness. We speculate that the Arnold-Chiari malformation interferes with central chemosensitivity (hypercapnic ventilatory response) and central integration of chemoreceptor output. PMID- 2585226 TI - Long-term ventilatory support in spinal muscular atrophy. AB - Before ethical issues regarding prolonging life in patients with degenerative disease can be considered, the quality of life with medical intervention must be delineated. We have followed 15 patients with spinal muscular atrophy who have been treated with mechanical ventilation. They have received assisted ventilation for an average of 8 years 10 months (range 5 months to 23 years 10 months). Three of the patients required full-time ventilator assistance at the time of initiation of ventilation; the remaining 12 used nighttime ventilation for an average of 8 years 7 months. Nine patients continue to receive nighttime ventilation only. Two patients died after 5 years and 14 years of assisted ventilation, respectively. Of the 10 patients more than 18 years of age, three graduated from college, two are in college, three graduated from high school, and two completed eleventh grade. One patient is a mother of a healthy child. Two patients are employed, and two others have found fulfilling volunteer work. Ventilator support has not significantly interfered with these patients' plans and expectations. PMID- 2585227 TI - Meconium contamination of the neonatal middle ear. AB - The neonatal middle ear and mastoid cavity are frequently contaminated by cells and hair of the amniotic fluid. This amniotic fluid cellular content provokes a foreign body inflammatory reaction that can persist for months. To evaluate whether clinical and postmortem findings might correlate with the amount of amniotic fluid cellular content in the middle ear, we compared temporal bones of nine patients born through meconium-contaminated amniotic fluid with those of 10 patients born through clear amniotic fluid. All patients were examined at less than 17 days postpartum and provided 37 temporal bones for histologic analysis. The volume of contaminant was quantified for each patient. The cases were arranged according to volume of contaminant in the middle ear and compared with clinical information and autopsy findings. Patients with larger volumes of contaminant in the middle ear were born through thick, meconium-stained amniotic fluid (1.9-38 mm3; average 9.3 mm3). Conversely, patients with lesser volumes of contaminant in the middle ear were born through unstained amniotic fluid (none to 3.2 mm3; average 0.9 mm3). We speculate that patients born through thick, meconium-stained amniotic fluid may be at greater risk of sequelae such as otitis media from this foreign body inflammatory reaction in the middle ear and mastoid cavity. PMID- 2585228 TI - Uric acid excretion in children with urolithiasis. AB - Urinary uric acid excretion was assessed in 38 children to determine whether hyperuricuria was a risk factor in children with urolithiasis. Uric acid excretion (measured per deciliter glomerular filtration rate), and fractional excretion of uric acid were similar in 27 children with hypercalciuria and calcium oxalate urinary stones, in six children with idiopathic calcium oxalate urolithiasis, and in five with uric acid urolithiasis, of whom four were white boys and one was an Asian girl. One boy with a urate stone had cystinosis. Serum uric acid concentrations exceeded 6.0 mg/dl (360 mumol/L) in two children with hypercalciuria and in two patients with idiopathic calcium oxalate urolithiasis. None of the children with calcium urolithiasis had excessive urinary excretion of uric acid. In children with hypercalciuria, uric acid excretion did not change significantly when dietary sodium was increased from 1.0 to 5.0 gm/1.73 m2. We conclude that excessive urinary uric acid excretion is seldom an additional risk factor in children with calcium urolithiasis and that dietary sodium chloride does not have a strong influence on urinary excretion of uric acid in children with hypercalciuria. PMID- 2585230 TI - Predicting traffic injuries in childhood: a cohort analysis. AB - Data from a sample of more than 16,000 children born in the United Kingdom in 1958 were studied to identify factors that may affect the risk of having a traffic injury. Five sets of risk factors were examined: physical, developmental, educational, behavioral, and family. Information about these factors were obtained systematically from parents, teachers, and physicians when the children were 7 and 11 years of age. The results were related to traffic injuries occurring for the first time during each subsequent 4-year period. Between 8 and 11 years of age, 431 children had a traffic injury requiring medical attention, and between 12 and 16 years the number was 590. Logistic regression analyses identified a small number of factors associated with injuries, which varied according to the age and gender of the child. When all these factors were entered into a final model, only five remained: fidgety, abnormal behavior, and three measures of family disruption or disadvantage--crowding, family problems, and being removed from the family and placed in the care of the local authority. These findings suggest that it may be unwise to place much reliance on "high risk" preventive strategies by measures of this kind. Instead, more emphasis should be placed on community-based passive and environmental strategies. PMID- 2585229 TI - Family support and parenting education in the home: an effective extension of clinic-based preventive health care services for poor children. AB - A study was designed to assess the effect and cost of providing parenting and child care education in the home to inner-city mothers of poor infants receiving comprehensive health care in a large federal Children and Youth Program. Randomly selected, healthy neonates weighing more than 2000 gm and born to black women aged 18 years and older (n = 131) and to comparable control subjects (n = 132) were followed for a mean of 23.4 and 22.9 months, respectively. A community woman, with educational, social service, and medical backup support from the Children and Youth Program, made home visits 7 to 10 days after the birth and between regularly scheduled well-child-care visits. Improved compliance with well child care, fewer illness visits, and sharp reductions in hospitalization and in neglect or abuse were found in the visited group compared with the control group, and substantial cost was averted. Prerequisite and concomitant to focusing the mother's attention on the infant was the resolution of the numerous crises and survival problems experienced by these poor women. Only then was parenting education accepted by the mother. PMID- 2585231 TI - Spontaneous tumor necrosis factor production in Kawasaki disease. AB - Tumor necrosis factor production by peripheral blood mononuclear cells was measured in 18 patients with Kawasaki disease. In patients studied during the acute febrile phase of their disease, there was increased spontaneous TNF production (mean 26.9 +/- 40.3 U/ml) compared with that of control subjects (1.0 +/- .86 U/ml) (p less than or equal to 0.025). Spontaneous TNF production by patients tested in the subacute or convalescent phase of the illness was significantly lower than that in patients tested during the acute illness (p less than or equal to 0.025). In all patients studied with serial acute and subacute convalescent samples, TNF production was normal in the follow-up samples. Because TNF is a potent mediator of inflammation and causes damage to vascular endothelial cells, we suggest that TNF may be important in the pathogenesis of both the immune activation and endothelial cell damage characteristic of this illness. PMID- 2585232 TI - Lymphocyte phenotype does not predict immune function in pediatric patients infected with human immunodeficiency virus type 1. AB - To determine whether assays of lymphocyte phenotype were predictive of antigen specific immunologic function in children infected with human immunodeficiency virus type 1 (HIV-1), we compared the antigen-specific cellular and humoral functions (tetanus toxoid-induced T lymphocyte blastogenesis and anti-tetanus toxoid antibody) with the patients' T lymphocyte phenotype, determined at the same time. Although both HIV-1-infected patient populations studied (pediatric hemophilia patients and other pediatric patients) had decreases in the values determined by their functional and phenotypic assays, no association between the functional and phenotypic assays was demonstrated. Thus some HIV-1-infected patients with a normal phenotype had no antigen-specific function, whereas other patients with a markedly abnormal T lymphocyte phenotype had normal antigen specific T lymphocyte function. These results indicate that the assessment of HIV 1-infected patients should include assays of antigen-specific immune function in addition to assays of T lymphocyte phenotype. PMID- 2585233 TI - Transfusion of infants with activation of erythrocyte T antigen. AB - A protocol for transfusion of infants with erythrocyte T-antigen activation was evaluated for safety and effectiveness in a prospective, 3-year, sequential series of 1672 infants admitted for intensive care. Erythrocyte T antigens are activated by enzymes produced by clostridia or other bacteria in infants with sepsis, often in association with necrotizing enterocolitis. Transfusion of these infants with blood products containing plasma carries the risk of causing intravascular hemolysis. Our transfusion protocol included testing for T-antigen activation, restricting transfusion of patients with activated T antigens to washed erythrocytes or washed platelets whenever possible, and selecting donors with low-titer anti-T when plasma-containing blood products were required. In this series, 10 patients had T-antigen activation, including four with clostridial infections. Severe hemolysis occurred in one patient who received plasma before T-antigen activation developed. Of five patients who received low titer anti-T plasma, mild hemolysis occurred in three and no hemolysis in two. Four patients who received no plasma-containing blood products experienced no hemolysis. Used cautiously, this protocol allows a full range of transfusion therapy to infants with T-antigen activation. PMID- 2585234 TI - Outcome of pectus excavatum in patients with Marfan syndrome and in the general population. AB - We reviewed the records of 28 patients with Marfan syndrome and 30 age-matched control patients with presumed isolated pectus excavatum to determine the outcome of surgical repair of the pectus deformity in Marfan syndrome. One third of the patients with Marfan syndrome underwent repair of the pectus excavatum before diagnosis. Of the 30 patients with "isolated" pectus excavatum, 17 had findings by history or physical examination, such as mitral valve prolapse, scoliosis, or a relative with pectus excavatum, suggestive of an underlying disorder of connective tissue. Pectus excavatum of more than moderate severity recurred in 11 of 28 patients with Marfan syndrome and was associated with young age at initial surgery and lack of temporary internal stabilization of the chest after surgery. Only two of the control patients had recurrence of the defect; one of these patients had findings suggestive of an underlying heritable disorder of connective tissue. We conclude that pectus excavatum may indicate the presence of an underlying heritable disorder of connective tissue such as the Marfan syndrome. In patients with Marfan syndrome, and possibly other inherited connective tissue disorders, surgical repair should be delayed if possible until skeletal maturity is nearly complete and should employ internal stabilization. PMID- 2585235 TI - Nutrient intake and growth performance of older infants fed human milk. AB - STUDY OBJECTIVE: To determine whether the ad libitum addition of solid foods to the diet of exclusively human milk-fed infants will increase energy intake and reverse the decline in weight-for-age percentiles observed during the exclusive breast-feeding period. DESIGN: Weekly or biweekly measures of growth were made longitudinally on a cohort of infants from birth to 36 weeks of age, and monthly measures of nutrient intake were made from 16 weeks of age until 10 weeks after solid foods were introduced into the diet. SUBJECTS: Volunteer mother-infant pairs from middle and upper income groups who met entry criteria, including the intention to breast-feed exclusively for at least for 16 weeks; 58 pairs entered and 45 pairs completed the study. INTERVENTION: Solid foods were introduced at a time determined by the mother and the pediatrician; solid foods from controlled lot numbers were provided for each infant. MEASUREMENTS AND MAIN RESULTS: After solid foods were added, daily human milk intake declined at a rate of 77 gm/mo (p less than 0.001). Milk composition did not change during the observation period. Daily total energy intake increased 29 kcal/mo, but no changes were noted in energy intake when consumption was normalized for body weight. Weight (National Center for Health Statistics percentiles) at 28 weeks was 13 percentiles lower than that at birth, and length at 28 weeks was 1 percentile lower than at week 1. Weight and length percentiles at 28 weeks, when compared with peak values at 8 weeks, had dropped 19 and 14 percentiles, respectively. CONCLUSIONS: Energy intake of human milk-fed infants did not increase after solid foods were added to their diet but was maintained at approximately 20% below recommended levels. Energy intake appeared to reflect infant demands. These data suggest that the recommendations for the energy requirements of infancy should be reevaluated. The growth pattern of exclusively breast-fed infants differs from that of the National Center for Health Statistics reference population. These observations raise questions about the adaptive response of human milk-fed infants to different levels of energy intake and about the estimations of energy requirements based on the sum of basal metabolism, activity, growth, and diet induced thermogenesis. PMID- 2585236 TI - Intravenously administered immune globulin for premature infants: a time to wait. PMID- 2585237 TI - Use of intravenously administered immune globulin to prevent nosocomial sepsis in low birth weight infants: report of a pilot study. AB - To evaluate the use of intravenously administered immune globulin (IVIG) for prevention of sepsis in preterm infants, we administered IVIG in a protocol designed to maintain a therapeutic serum "target level" of 700 mg/dl. The 200 patients who were eligible for the study (600 to 2000 gm birth weight) were monitored throughout their initial hospitalization. Of these, 115 patients were randomly assigned in a double-blind, controlled trial to treatment and placebo groups. The remaining 85 infants were not randomly assigned to a group, by parental request, but were followed and analyzed separately. In one patient who received IVIG, transient tachycardia and a decrease in blood pressure developed during an infusion; resolution occurred promptly after the infusion was discontinued. No persistent hepatic or renal abnormalities were noted in either the IVIG- or the placebo-treated group. There were seven episodes of sepsis in the placebo group and nine in the group whose parents refused consent to the study. No infant who received IVIG acquired nosocomial sepsis (p less than 0.01). All patients in the placebo group in whom sepsis developed had serum IgG levels less than 400 mg/dl at the time sepsis developed. Serum IgG levels were maintained near 700 mg/dl in patients who received IVIG. These data indicate that administration of sufficient IVIG to maintain target serum IgG levels throughout hospitalization may decrease the incidence of nosocomial sepsis in preterm infants. PMID- 2585239 TI - Microencapsulation using poly(L-lactic acid). I: Microcapsule properties affected by the preparative technique. AB - Microcapsules were prepared using a poly (L-lactic acid) (L = PLA), mol. wt. 43,200, by an emulsification and solvent evaporation technique. Phenobarbitone (PB) was used as a reference drug, (core to polymer ratio, 1:1). Both the o/w and w/o emulsion system were investigated in order to study microcapsule properties affected by the preparative technique. In the o/w system, dichloromethane (DCM) was used to dissolve L = PLA and PB and the resulting solution was dispersed in 1 per cent aqueous gelatin solution. Subsequent evaporation of the DCM resulted in the formation of microcapsules. PB was found to be poorly encapsulated within microcapsules from this o/w system. PB content in the microcapsules was found to improve using PB saturated aqueous gelatin solution as the continuum. In the w/o system, acetonitrile (AN) was used as a solvent for L-PLA and PB and light liquid paraffin (LLP), containing 2 per cent w/w Span 40, as the continuous phase. PB loading in the microcapsules was found to be very high from this w/o system. Microcapsules from the o/w system were very small compared to microcapsules obtained from the w/o system. The morphology of the microcapsules and the surface properties were found to be affected distinctly by the two techniques. Microcapsules from the o/w system showed a smooth and less porous surface, whereas a highly porous surface containing embedded PB crystals was found in the microcapsules from the w/o system. PMID- 2585238 TI - Accuracy and reliability of glucose reflectance meters in the high-risk neonate. PMID- 2585240 TI - Sterilization of contrast media (Isovist) containing liposomes by ethylene oxide. AB - Liposomes containing Isovist were prepared by controlled detergent dialysis as well as by reverse phase evaporation. After preparation these liposomes were lyophilized and then submitted to sterilization by ethylene oxide. Prior to lyophilization, trehalose was added as a protective agent to preserve the size of the liposomes. After each step in the preparation size distribution was determined by photon correlation spectroscopy. The computer program CONTIN was adapted for the data analysis and proved to be applicable for polydisperse solutions of liposomes. Neither freeze-drying nor sterilization had negative effects on the morphological quality of the samples when using 4 g of trehalose per 1 g of lipid. In addition, the quality of the liposomes was controlled by scanning electron microscopy. At the end of seven days, no growth of microorganisms occurred in any of the samples. PMID- 2585241 TI - In vivo characterization of indomethacin magnetic polymethyl methacrylate nanoparticles. AB - The in vivo magnet responsiveness and kinetics of distribution of indomethacin entrapped in a magnetic and plain carrier were characterized by rat tail model and periodic monitoring of drug concentration in various visceral organs after intraarterial and intravenous administration respectively. Up to 60 min post injection time 60-fold higher concentrations could be achieved in tail target segment which resulted in considerably reduced drug concentration in other organs as evinced by data from control rats. Following normal administration (no magnetic field applied) the drug concentration was higher in the liver and spleen where endocytosis and phagocytosis occur. The magnetic nanoparticle of indomethacin holds promise for selective targeting under magnetic field of 8000 Oe strength. PMID- 2585243 TI - Effect of electrolytes, stirring and surfactants in the coacervation and microencapsulation processes in presence of gelatin. AB - The objectives of the present study were to investigate the parameters affecting simple coacervation and the ability to encapsulate oleic acid using this technique. Coacervation has been achieved using different types of gelatin (bloom number, charge) and various electrolytes. The electrolytes used for the coacervation can be divided into three groups: (1) inert salts; (2) phase separation inducers, (a) precipitation inducing agents (PIA), and (b) coacervation inducing agents (CIA); (3) coacervation inhibiting agents. The encapsulation of oleic acid was evaluated with two types of gelatin and various emulsifiers (anionic, cationic and nonionic). For positively charged gelatin, it was found that the encapsulation is incomplete in presence of cationic emulsifiers. For negatively charged gelatin no general trend was observed. The stirring rate for each step of the preparation of the microcapsules was evaluated. It was found that high stirring is essential only in the cooling stage. The study was carried out in view of encapsulation of particular bacteria dispersed in the oil phase. PMID- 2585242 TI - Production of hydrogen sulphide in milkfat-coated microcapsules containing Brevibacterium linens and cysteine. AB - Milkfat-coated microcapsules containing Brevibacterium linens and cysteine were used to produce hydrogen sulphide, one of Cheddar cheese flavour compounds. Hydrogen sulphide production was substantially reduced and delayed in the encapsulated system as compared with that of the unencapsulated system. Hydrogen sulphide was not produced aerobically whereas substantial amounts of hydrogen sulphide were produced in a nitrogen purged system. The inhibitory effect of the initial aerobic condition disappeared after 8 days of incubation. In spite of the lag in hydrogen sulphide production under aerobic conditions almost the same amount of hydrogen sulphide was produced in oxygen purged samples as in the nitrogen purged samples after 10 days of incubation. Moderate heat treatment (2 min at 58 degrees C) of cell suspension-milkfat-emulsion increased subsequent hydrogen sulphide production. The optimum pH and temperature for hydrogen sulphide production from cysteine by Brevibacterium linens were 6 degrees C and 32 degrees C, respectively. Antioxidants BHT, BHA and ascorbic acid had negligible effects on production of hydrogen sulphide in the encapsulated system. PMID- 2585245 TI - Evidence for spread of the human immunodeficiency virus epidemic into low prevalence areas of the United States. AB - Reports of an increased proportion of AIDS cases occurring in small and medium sized cities suggest that the HIV epidemic may be spreading into locations that were previously characterized by their low HIV antibody prevalences. Studying the question of the geographic spread of the HIV infection epidemic (rather than the AIDS epidemic) has been difficult largely because most serial seroprevalence data have been gathered from cohorts of high risk individuals (e.g., homosexual/bisexual cohorts) in New York City, San Francisco, and other geographically circumscribed areas. The U.S. military applicant HIV screening data were used in the current report to examine rates and 24 month temporal trends in geographic areas characterized by their HIV endemicities. The data examined concern the seven most populous states and four hyperendemic metropolitan areas located within those states (New York City, Miami, Houston, and San Francisco). In the nonepidemic regions, seroprevalence rates increased among black and white applicants. In the four epidemic urban areas, only young black applicants had higher HIV seroprevalence rates during the second 12 month period. Six of the seven nonepidemic regions had positive HIV seroprevalence trends, and these trends were significant in Florida, California, Texas, Illinois, and Ohio. The increases in these regions were greater for young blacks (30% excess for year 2 vs. year 1) compared to young whites (12% excess for year 2 vs. year 1). These data provide evidence of birth year specific increases in seroprevalence over time occurring in presumed low HIV prevalence areas. These increases cannot be due to, but are observed in spite of, biases associated with increasing self-selection over time. PMID- 2585244 TI - Safety comparison of insecticide microencapsulation and investigation of its mechanism. AB - Four kinds of microencapsulated insecticides were prepared with fenthion, mevinphos, acetofenate and methylparathion. From observations made after the experiment it was found that type II microcapsules with polyurea capsule walls formed by interfacial polymerization had a special advantage: they had greatly enhanced safety in mice when administered via mouth, respiratory tract and skin. Type I microcapsules, with capsular walls of gelatin and Arabic gum formed through complex condensation, had no safety protection with oral administration. The mechanism of safety enhancement associated with type II microcapsules depends mainly on maintenance of microcapsule integrity within the digestive tract; type II microcapsules rarely disintegrated in the gastrointestinal tract and only about 5 per cent were ruptured. Of the small quantity of insecticide that leaked through the ruptured capsule walls, the amount absorbed by the digestive tract was not sufficient to kill the mice before the microcapsules were discharged in faeces--The amount of discharge within 48 hours exceeded 80 per cent. Administration of large numbers of microcapsules was necessary before sufficient insecticide could be absorbed by the digestive tract to cause lethal dosage; on post-mortem examination some microcapsules were found intact in the stomach and small intestine. Type I microcapsules, however, were totally disintegrated in the digestive tract and no traces could be found in the faeces; therefore their drug safety could not be increased. PMID- 2585247 TI - Human retroviruses HTLV-I, HIV-1, and HIV-2 and neurological diseases in some equatorial areas of Africa. AB - HTLV-I is associated with tropical spastic paraparesis (TSP) in the Caribbean area and with certain chronic myelopathies termed HAM (HTLV-I-associated myelopathy) in Japan. In order to investigate the situation in Africa, we tested for HTLV-I, but also for HIV-1 and HIV-2 antibodies, 94 patients with epidemic spastic paraparesis (ESP) from Zaire and Tanzania, 26 cases of sporadic spastic paraparesis (SSP) and 21 cases of tropical ataxic neuropathy (TAN), both from Ivory Coast, and 319 unselected neurological patients from Ivory Coast, Congo, and Tanzania. While none of the 94 ESP cases nor any of the 21 TAN patients exhibited antibodies to any retrovirus, 4 of the 26 sporadic spastic paraparesis patients had high HTLV-I antibodies in their sera and cerebrospinal fluid (CSF). Three of those were clinically and immunologically identical to TSP, as observed in persons from the Caribbean region, and the fourth case, a poorly explored chronic pyramidal syndrome, could also represent a TSP. Only one of these four cases originally had HIV-1 antibodies. Among the 319 unselected patients, only 5 (1.6%) had HTLV-I antibodies, but 32 (10%) had HIV-1 antibodies and 14 (4.4%) had HIV-2 antibodies, with a number of combined infections, indicating that retroviruses represent potentially important etiological agents for African neurological diseases. PMID- 2585246 TI - Introduction of HIV infection among intravenous drug abusers in low prevalence areas. AB - To explore the introduction of human immunodeficiency virus (HIV) infection into intravenous drug abusing populations, risk behaviors of 1,154 intravenous drug abusers (IVDAs) in four U.S. cities with low prevalence of IVDA/HIV infection (0.9-13.0%) were examined. Seropositive subjects (N = 54) were compared with demographically matched seronegative controls regarding drug use practices, homosexual contact, blood transfusions, risk behaviors while traveling or living in high prevalence areas, and acquaintance with persons with AIDS. With the exception of needle sharing with homosexual/bisexual males, no differences in risk behaviors were found between seropositive subjects and matched seronegatives. Seropositives were substantially more likely than matched seronegatives to report having shared a needle with a homosexual or bisexual male, suggesting that needle sharing between homosexual/bisexual IVDAs and heterosexual IVDAs may be an important means by which HIV is introduced among heterosexual IVDAs in low prevalence areas. PMID- 2585248 TI - Cutaneous delayed-type hypersensitivity in patients with human immunodeficiency virus infection in Zaire. AB - Cutaneous delayed-type hypersensitivity (DTH) reactions were assessed by the CMI Multitest (Merieux, Lyon, France) in patients with different stages of human immunodeficiency virus (HIV) infection in Kinshasa, Zaire. Skin tests were read after 48-72 h. A reaction to an antigen was considered positive if there was induration of greater than 2 mm. Cutaneous anergy occurred more often in HIV seropositive patients than in healthy controls (p less than 0.001) and was most prevalent in patients with advanced HIV illness. HIV-seropositive patients with a positive tuberculin reaction were more likely to have active tuberculosis (TB) than HIV-seropositive patients without a positive tuberculin reaction (p less than 0.001). Therefore, a TB diagnosis should be pursued in HIV-seropositive patients with a positive tuberculin reaction. PMID- 2585249 TI - The potential for homeostatic regulation of the X region proteins of the human T cell leukemia virus type I. AB - The human T cell leukemia/lymphoma virus type I (HTLV-I) encodes two regulatory proteins, a 42 kDa trans-activator protein (p42tax) and a 27 kDa protein (p27rex), required for virus capsid protein synthesis. The experiments described here show that the p27rex protein negatively regulates the expression of the p42tax protein by suppressing the accumulation of the spliced messenger RNA from which the p42tax and p27rex proteins are made. It is proposed that such an interplay between the two regulatory genes results in a homeostatic system that may regulate the rate of viral replication as well as the growth of HTLV-I transformed cells. PMID- 2585250 TI - Medical Research Council AIDS Directed Program: program plan and research opportunities. AB - In 1987 the U.K. Medical Research Council established a Directed Programme of AIDS Research, the primary objective of which is the development of vaccines and therapeutic approaches against HIV infection and AIDS. The Programme's activities have been rapidly built up and by mid-1989 comprised some 130 individual research projects. The Programme provides the framework for a cohesive approach to AIDS research, comprising a clearly defined scientific development plan, the central provision of resources including laboratory reagents and specialized laboratory facilities and special arrangements for interaction with industry and for international collaboration and training. This article describes the organization, scientific strategies and progress of the Programme. PMID- 2585251 TI - Barriers to child psychiatric nursing research. Issues and opportunities to advance the field. PMID- 2585252 TI - Are adolescents being hospitalized unnecessarily? The current use of hospitalization in psychiatric treatment. AB - The increasing use of hospitalization in adolescent psychiatric treatment is arousing public and professional concern. Numerous factors may be contributing to inappropriate or unnecessary inpatient care. The misuse of hospitalization ultimately may lead to reduced third-party coverage for needed care. Nurses can help promote adherence to guidelines for hospitalization, such as those set by the American Academy of Child and Adolescent Psychiatry. PMID- 2585253 TI - Comparison of child adaptation to epilepsy and asthma. AB - Self-concept, home behavior and school behavior of 128 children with epilepsy and 126 children with asthma were measured in order to compare and contrast differences in psychosocial adaptation. Results indicated that children with epilepsy were experiencing significantly poorer psychosocial adaptation (p less than .001) in all three areas. An exploration of gender differences across groups indicated that girls were more at risk for the home behavior problems of depression, somatic complaints, social withdrawal and hyperactivity than boys. Clinical implications for interventions with these two populations are discussed. PMID- 2585254 TI - Crisis in psychiatric nursing education: the paradox of shortage and cutbacks in psychiatric nursing education programs. PMID- 2585255 TI - The "Life Plant" and psychiatric mental health nursing. PMID- 2585256 TI - Coping with cutbacks in psychiatric nursing education programs. PMID- 2585258 TI - Child psychiatric nursing. PMID- 2585257 TI - Socialization groups in a school outreach program. PMID- 2585259 TI - [Synthesis of thieno[2,3-d]pyrimidine derivatives and their antifungal activities]. AB - 4-Chlorothieno[2,3-d]pyrimidines were prepared by the chlorination of 4-oxo-3,4 dihydrothieno[2,3-d]pyrimidines with phosphoryl chloride. 4-Oxo-3,4,5,6,7,8 hexahydro[1]-benzo- and 4-oxo-6-phenylthieno[2,3-d]pyrimidine were synthesized by the cyclization of 2-acylaminothiophene-3-carboxamide derivatives with base. 2 Methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine was prepared by the treatment of 2-methyl-4-trichloromethylthieno-[2,3-d]pyrimidine with sodium hydroxide in aqueous methanol. A series of 4-alkylamino- and 4-arylaminothieno[2,3 d]pyrimidines were synthesized by the nucleophilic substitution of 4 chlorothieno[2,3-d]pyrimidines with various amines. These compounds were evaluated for antifungal activity against Piricularia oryzae. The preventive effects on Rice blast, Sheath blight, and Cucumber powdery mildew were also determined by pot tests. PMID- 2585260 TI - [Choleretic effects of methanol extracts obtained from various Chinese traditional medicine]. AB - Choleretic effects of 60 kinds of Chinese traditional medicine frequently used in clinical practice were investigated. Consequently, significant effects of choleretics were found in the methanol extracts of Ko-so-san, Intinko-to, Saiko seikan-to, Hange-koboku-to, Antyu-san, Syo-kankyo-to, Keisi-syakuyaku-timo-to, Senkan-meimoku-to, Bohu-tusyo-san, Juzen-taiho-to, Jumi-haidoku-to Kami-syoyo-san and Hange-syasin-to. Water extracts of these Chinese traditional medicine had no such effect. Alteration of excretion of various biliary components after administration of the methanol extracts with the choleretic effect was examined, and with all medicines, bile acid excretion decreased and sodium and potassium excretions increased. Therefore, a medicine inducing choleresis involves some selective increases in the bile acid-independent fraction of bile flow. And after administration of methanol extracts of Keisi-syakuyaku-timo-to and Bohu-tusyo san, lithogenic index, an index of saturation level of cholesterol, decreased significantly. Therefore, with these medicines, a dissolving effect on cholesterol gallstone is expected. PMID- 2585261 TI - [Application of multi-lines fitting technic for ethenzamide elimination with capacity-limited process in the rabbit plasma]. AB - Intravenous and oral administrations of ethenzamide (EZ) were carried out in the rabbit, and elimination process pharmokinetically discussed. When the drug dose increased, plasma clearance and extent of bioavailability were reduced and plasma peak times delayed after oral dose of EZ. Michaelis-Menten type elimination parameters were estimated from the plasma concentration-time profiles after intravenous dosing of EZ. The first-order absorption rate constant (ka), hepatic available fraction (FH) and approximate elimination rate constant (K) for hepatic first-pass metabolism of EZ were estimated using computer multi-lines fitting technique by iterative nonlinear least squares regression program, MULTI (RUNGE). PMID- 2585262 TI - Effect of probenecid on the renal and nonrenal clearances of zidovudine and its distribution into cerebrospinal fluid in the rabbit. AB - The effect of probenecid on the renal excretion of zidovudine (3'-azido-3' deoxythymidine; AZT) and its distribution into CSF was studied in the rabbit. Although probenecid is chemically unrelated to AZT, it has been shown that probenecid inhibits AZT elimination in Acquired Immunodeficiency Syndrome (AIDS) patients. The effect of probenecid on the renal clearance of AZT after an iv bolus dose was studied in crossover experiments in the absence (control) and the presence of a continuous iv infusion of probenecid. Probenecid coadministration increased the AZT plasma AUC by 70%, by proportionally decreasing the total body clearance. The renal clearance decreased by 50%. The effect of probenecid on the renal clearance of AZT at steady state was studied by measuring the renal clearance of AZT at different steady-state plasma probenecid concentrations. The renal clearance of AZT decreased with increasing probenecid concentration, suggesting competitive inhibition of the secretion of AZT in the renal tubule. The relationship between AZT renal clearance and probenecid plasma concentrations, during and after probenecid iv infusion in conscious and in anesthetized uretercannulated rabbits, showed hysteresis, indicating that probenecid plasma concentration is different from the concentration at the site of interaction. This suggests the presence of an effect compartment for the inhibition of AZT renal excretion by probenecid. The effect of probenecid on the CSF distribution of AZT was also studied in the rabbit. Probenecid coadministration caused a sevenfold increase in the AZT AUCCSF in probenecid treated rabbits when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585263 TI - Characterization of the oral absorption of beta-lactam antibiotics. II. Competitive absorption and peptide carrier specificity. AB - The beta-lactam antibiotic oral absorption pathway is studied using a single-pass perfusion technique in the rat small intestine. Beta-lactam antibiotic absorption in the presence of amino acids, small peptides, and other beta-lactams is modeled using a simple competitive inhibition boundary condition at the intestinal wall, with a corrected value for the intestinal wall concentration, Cw, derived from the modified boundary layer analysis. The model-predicted permeability in the presence of an inhibitor is used to characterize the beta-lactam antibiotic intestinal carrier system. Several concentrations of cephalexin, coperfused with a constant concentration of cefadroxil (equal to its Km), showed that the Km of cephalexin approximately doubled from 7.2 (+/- 1.1) to 18.8 (+/- 4.1) mM; Jmax remained unchanged at 9.2 (+/- 1.2) and 11.1 (+/- 2.1) mM; and the carrier permeability, Pc, was reduced by approximately 50% from 1.11 (+/- 0.10) to 0.59 (+/- 0.04), consistent with competitive absorption kinetics. The predicted in situ wall permeability, the mean value of P*w, of beta-lactams perfused in the presence of other beta-lactams was calculated and then compared with experimentally determined values. For cefadroxil, P*w = 0.27 (+/- 0.04), the mean value of P*w = 0.29; for cefatrizine, P*w = 0.67 (+/- 0.09), the mean value of P*w (+/- 0.09), the mean value of P*w = 0.59; and for cephalexin, P*w = 0.56 (+/- 0.05), the mean value of P*w = 0.59.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585264 TI - Atropine absorption after intramuscular administration with 2-pralidoxime chloride by two automatic injector devices. AB - Compared with manual intramuscular injection, automatic injector delivery substantially enhances drug absorption rate. We examined the effect of two types of automatic injector delivery of two drugs which are components of the standard antidote to anticholinesterase poisoning and which have been previously shown to have a reduced absorption rate when mixed together in a manual injection. In crossover experiments one week apart, 20 nonsmoking healthy young male humans (ages 20-30) were studied after citrated atropine (6.9 mumol/0.7 mL) and pralidoxime chloride (3.5 mmol/2.0 mL; PAMCL) were injected sequentially into a single intramuscular site by either a multichambered autoinjector or a device which delivers the drugs into two separate intramuscular sites (MARK I). Atropine absorption was assessed by the appearance of atropine in the serum and by changes in heart rate, salivary secretion, pupil diameters, and near vision accommodation. Atropine absorption was significantly greater in the first 30 min following injection with the MARK I. The results of this study suggest that: (1) the MARK I device produces a faster absorption of atropine, probably through some combination of its broader dispersal of atropine in the muscle site and its separation of atropine from the PAMCL; (2) salivary secretion may be the most convenient and sensitive marker of atropine action; and (3) the 6.9- mumol (2-mg) dose of atropine delivered by either autoinjector gives near maximal antisialogogue activity in normal male humans. PMID- 2585265 TI - Improved anticonvulsant activity of phenytoin by a redox brain delivery system. II: Stability in buffers and biological materials. AB - The stability of nine chemical delivery systems (CDSs) for phenytoin (DPH) was studied in aqueous buffers and in biological materials. The systems were based on a dihydropyridine in equilibrium quaternary pyridinium salt redox pair attached to 3-(hydroxymethyl)phenytoin via an ester linkage. The pyridinium derivatives released DPH in aqueous buffers and their hydrolytic reactivity was consistent with their chemical structure. Although in rat blood and plasma all pyridinium esters hydrolyzed rapidly, there was a wide range in the hydrolysis rates in rat brain homogenate. The sterically hindered 1-alkylcarboxynicotinamide was the least reactive ester (t1/2 = 98.2 min), while the trigonellylglycolate ester was the fastest to hydrolyze enzymatically (t1/2 = 2 min) in rat brain homogenate. In acidic media, the major products of all dihydropyridine esters were the corresponding water adducts, the 6-hydroxy- 1,4,5,6-tetrahydropyridines. These adducts were of no significance in biological materials. After comparison of the relative stability of the corresponding pairs of dihydropyridine and pyridinium ion in brain homogenate and the absolute stability of the various dihydropyridines, two CDSs were chosen for further in vivo evaluations. The CDSs chosen were the dihydrotrigonellinate ester and its 6-methyl derivative. PMID- 2585266 TI - Toxicity screening of N-alkylazacycloheptan-2-one derivatives in cultured human skin cells: structure-toxicity relationships. AB - A number of N-alkylazacycloheptan-2-one derivatives, with the hydrocarbon chain lengths systematically varied from C2 to C16, were tested for their possible skin toxic effects. For this purpose, three in vitro cytotoxicity assays were used: (1) inhibition of proliferation of cultured human fibroblasts and keratinocytes; (2) inhibition of collagen contraction by human fibroblasts; and (3) cell morphology changes in confluent cultures of human fibroblasts and keratinocytes. With all assays used, the toxicity of N-alkylazacycloheptan-2-one derivatives increased from C2 to C8, remained constant at a hydrocarbon chain length between C8 and C14, and subsequently decreased with increasing alkyl chain length. A similar trend has been observed for flux enhancement of nitroglycerine in the presence of these N-alkylazacycloheptan-2-one derivatives, suggesting that with these compounds a parallelism exists between skin cell toxicity and penetration enhancing capacity. Since for practical use it is preferable to find a balance between skin toxicity and the penetration enhancement effect of a particular enhancer, it would be advisable to do QSAR studies of this kind with a number of congeners of a particular compound in order to optimize the choice. In this particular case, further modification of the N-alkylazacycloheptan-2-one structure might lead to an even better choice than the often propagated dodecyl derivative. PMID- 2585267 TI - Kinetics of drug action in disease states. XXXII: Effect of experimental hypertension on the pharmacodynamics of phenobarbital in rats. AB - The purpose of this investigation was to determine the effect of experimental hypertension on the concentrations of phenobarbital required to produce a defined hypnotic effect (loss of righting reflex) in adult, female Lewis rats. Hypertension was induced with deoxycorticosterone acetate (DOCA), administered by im injection (first experiment) or by pellet implant (second experiment), and 1% NaCl in the drinking water. There were two control groups: one that received im injections of water or a drug-free pellet implant plus 1% NaCl in the drinking water, the other that received water injections or drug-free pellet implants and no NaCl in the drinking water. These treatments were carried out for 3 months and resulted in appreciable elevation of blood pressure and increased heart weight in the DOCA + NaCl-treated (but not in the NaCl alone) rats. All animals then received an infusion of phenobarbital until onset of loss of righting reflex. The concentrations of phenobarbital in the serum, serum water, brain, and CSF of the hypertensive rats at the pharmacologic endpoint did not differ significantly from corresponding concentrations in the control groups (except for a marginal difference of the drug concentration in serum water between the DOCA pellet group and the drug-free pellet control group). It is concluded that DOCA-induced hypertension has no apparent effect on the sensitivity of the central nervous system to the hypnotic action of a barbiturate in female rats. PMID- 2585268 TI - Effect of carrier dose on the multiple tissue disposition of doxorubicin hydrochloride administered via magnetic albumin microspheres in rats. AB - The effect of carrier dose on the multiple tissue disposition of doxorubicin hydrochloride has been investigated in rats. The drug was encapsulated in submicron magnetic albumin microspheres using a heat-denaturation technique. The rat tail was used as a target organ. Two groups of animals were administered 2.0 or 0.04 mg/kg of microsphere-entrapped drug via the ventral caudal artery, and the predefined tail target site was exposed to a 8000-G magnetic field for 30 min after dosing. In each group, the animals were sacrificed in triplicate over a 48 h period, and their various tissues were analyzed for drug concentration using reversed-phase ion-pair HPLC. The reduction in carrier dose was found to increase drug distribution as well as the targeting efficiency for the target tissue. The drug delivery to heart and liver was reduced. The significance of carrier dose in the targeted delivery of drugs is discussed. PMID- 2585269 TI - Competitive protein binding assay for piritrexim. AB - A competitive protein binding assay for piritrexim (PTX, 1) that makes use of a commercially available radioassay kit for methotrexate has been developed. After it is selectively extracted from plasma, PTX competes with [125l]methotrexate for binding to dihydrofolate reductase isolated from Lactobacillus casei. Free drug is separated from bound drug by adsorption to dextran-coated charcoal. Piritrexim is measurable over a range of 0.01 to 10.0 micrograms/mL in plasma with a coefficient of variation less than 15%. The limit of sensitivity of the assay is approximately 2 ng/mL. An excellent correlation between this assay and a previously published HPLC method was found. published HPLC method was found. PMID- 2585270 TI - Application of Bayesian estimation for the prediction of an appropriate dosage regimen of amikacin. AB - A Bayesian approach was developed to determine an amikacin dosage regimen to achieve the desired plasma concentrations for each patient. Statistical characteristics of pharmacokinetic parameters were first evaluated in a group of patients (reference population), which when combined with three individual plasma concentrations of drug led to a Bayesian estimation of individual pharmacokinetic parameters. By using these parameters, an individual dosage regimen was then established to avoid residual and peak amikacin concentrations of up to 3 and 25 micrograms/mL, respectively. In a test group of 33 patients, adapted amikacin dosage regimens ranged from 4 to 43 mg/kg/d, with schedules requiring up to four infusions per day. Infusion time varied from 40 min to 4 h. These differences in drug administration protocol result from the wide interindividual variability of amikacin pharmacokinetic parameters. Performance of the developed methodology was evaluated by computing bias and precision of the estimated total body clearance and of the trough and peak amikacin concentrations that were reached after dosage regimen determinations. PMID- 2585271 TI - Physical and structural comparison of oxyphenbutazone monohydrate and anhydrate. AB - Two crystal forms of oxyphenbutazone (a monohydrate and an anhydrate) were prepared by recrystallization. The forms were characterized by means of differential scanning calorimetry, thermogravimetry, infrared spectrophotometry, X-ray powder diffraction patterns, thermomicroscopy, scanning electron microscopy, as well as powder and intrinsic dissolution rates. The crystal structure of the anhydrate has been elucidated and compared with that of the monohydrate. PMID- 2585272 TI - Quantum mechanical study and nuclear magnetic resonance measurements of some alpha-arylcarboxyalkyl acids as anti-inflammatory agents. AB - The CNDO/2 quantum mechanical conformation method of analysis, charge density and protonation energy calculations, as well as 13C and 1H NMR measurements were carried out for ibufenac, ibuprofen, methylibuprofen, and for a series of alpha arylpropionic acids. It was found that the nature of the terminal lipophilic residue does not significantly influence the conformation of the alpha arylcarboxyalkyl acid side chain. The preferred conformational angle, for the torsion of the phenyl-C alpha bond, was found to be 90, 120, and 180 degrees in ibufenac, ibuprofen, and methylibuprofen, respectively. This conformational angle is calculated to be the same in all the alpha-arylpropionic acids. The protonation energies of the alpha-arylpropionic acids are correlated with the anti-inflammatory activity. It was found that the smaller the protonation energy, the larger the anti-inflammatory activity. PMID- 2585273 TI - Effect of pH and temperature on the solubility of a surface active carboxylic acid. AB - We have examined the effect of pH and temperature on the solubility of 3-(4 heptylbenzoyl) benzoic acid (1), a surface active carboxylic acid with a pKa of 4.83 and a critical micelle concentration (cmc) of 4 X 10(-4) M. Our results show that below a pH of 7.0 and a temperature of 50 degrees C, the solubility of 1 is less than the cmc; under these conditions, 1 behaves like a typical weak acid. Above pH 7.0, the solubility can equal or exceed the cmc, depending on the temperature, and dramatic deviations from typical weak acid solubility behavior are observed. The temperatures at which the solubility becomes equal to the cmc at various pH values were determined; these temperatures are termed apparent Krafft Points (KPapp). The KPapp varies with pH; the higher the pH, the lower the KPapp. For example, the KPapp at pH 7.0 is 49 degrees C, and at pH 8.0 is less than 5 degrees C. We report the pH-temperature-solubility relationship for 1 and use it to construct simple phase diagrams. PMID- 2585274 TI - Simultaneous determination of propranolol enantiomers in plasma by high performance liquid chromatography with fluorescence detection. AB - A simple, rapid, and sensitive assay for the simultaneous quantification of the ( )- and (+)-propranolol in human and dog plasma is described using a reversed phase high-performance liquid chromatography (HPLC) system with fluorescence detection. The method involves extraction of propranolol enantiomers from plasma into 1% 1-butanol in n-hexane at basic pH, followed by evaporation of the organic phase and the formation of diastereomeric derivatives with the chiral reagent (-) menthyl chloroformate. (+)-Flecainide is used as the internal standard. The limiting concentration of each enantiomer that can be detected is 1 ng/mL plasma. In six normal human volunteers, who received a single oral dose of 80 mg of racemic propranolol, the plasma levels of the (-)-enantiomer were always higher than those of the (+)-enantiomer with a mean (-):(+) ratio of 1.38. The half lives of both the enantiomers were similar (3.5 +/- 0.3 h). In six normal male mongrel dogs given a single intraportal dose of 40 mg of racemic propranolol, the plasma levels of the (-)-enantiomer were always lower than those of the (+) enantiomer with a mean (-):(+) ratio of 0.48. The half-life of the (-)-enantiomer (73.3 +/- 16.2 min) was shorter than that of the (+)-enantiomer (87.1 +/- 18.1 min). PMID- 2585275 TI - Analysis of pirprofen in cerebrospinal fluid, plasma, and synovial fluid by high performance liquid chromatography with electrochemical detection. AB - We describe a high-performance liquid chromatographic method, using electrochemical detection, for the determination of pirprofen in cerebrospinal fluid (CSF), plasma, and synovial fluid (SF). A C-18 column with a mobile phase containing acetonitrile acetate:phosphate buffer (pH 3.0) was employed. Samples were added with phosphoric acid, then extracted into dichloromethane, evaporated, and injected into the chromatograph. A detection potential of +0.85 V was applied on the basis of current-potential curves. Good linearity was found for each fluid in the expected range of therapeutic concentrations. The detection limit was 0.1 ng/mL for CSF, and 1 ng/mL for plasma and SF, with a recovery greater than 96% and intraday coefficient of variation less than 5% in all cases. The main advantages of this method include high specificity and sensitivity which allow the analysis of CSF and the use of small volumes of plasma and SF. The application of the method for the analysis of plasma and SF samples and the kinetic profile in CSF are shown. PMID- 2585276 TI - Synthesis and antimicrobial activity of new substituted 10-methyl-1,2-dihydro-1 oxo-1,2,4-triazino(4,5-a)indoles. AB - Ten new 4,8-disubstituted 10-methyl-1,2-dihydro-1-oxo-1,2,4-triazino(4,5 a)indoles (5 and 6) were prepared by refluxing various 5-substituted indole-2 carbohydrazides (4) with triethylorthoformate or triethylorthoacetate in dimethylformamide. These derivatives were evaluated for their antimicrobial activity. Some of the title compounds possess fairly potent antimicrobial activity. PMID- 2585277 TI - Uptake of O-alkyl erythromycin derivatives in the lung tissue and cells of rats. PMID- 2585278 TI - Kinetics of drug action in disease states. XXXV: Effect of hypovolemia on the pharmacodynamics of zoxazolamine in rats. PMID- 2585279 TI - Foot infections in patients with diabetes mellitus. AB - Foot infection is the single most common reason for hospitalization of the diabetic patient. A combination of host factors, including neuropathy, angiopathy, and immunopathy, combine to make the diabetic foot infection the most severe infection commonly seen by podiatrists. If inadequately treated, the likelihood of morbidity or mortality is high. The presence of anaerobic bacteria as a predominant type of organism makes diagnosis and antibiotic selection complicated. PMID- 2585280 TI - Diagnosis and treatment of staphylococcal diseases. AB - Staphylococcus is, by far, the most commonly seen organism in podiatric infections. Although common, staphylococcal infections are difficult to understand and treat. These bacteria have undergone significant changes in their pathogenicity and antibiotic susceptibility over the last few years. Methicillin resistant strains, once relatively rare, are becoming a major therapeutic dilemma in some centers. PMID- 2585281 TI - Use of ciprofloxacin in podiatric medicine. AB - Ciprofloxacin is the first of the new class of antibiotics known as fluoroquinolones to be approved for use in skin, skin structure, and bone and joint infections. It has an extremely broad spectrum and is particularly effective against traditionally resistant gram-negative rods. As an oral agent, it is as effective as parenteral drugs against a variety of organisms and diseases. Its spectrum, pharmacokinetics, and podiatric indications are reviewed. PMID- 2585282 TI - Adverse effects of antibiotics. AB - Adverse reactions to antibiotics comprise a number of classes of reactions, including toxicity, side effects, and allergy. Each one of these differs in its implication for treatment of the patient. The authors discuss some of the more common and unusual reactions to antibiotics frequently used in the practice of podiatric medicine. PMID- 2585283 TI - Positive identification based on radiographic examination of the leg and foot. A case report. AB - The authors have presented a forensic anthropology case that established positive identification by comparison of antemortem and postmortem x-rays of the legs and feet. This case illustrates one method of ascertaining the identity of a burned and skeletonized victim. By careful reconstruction and examination of the skeleton, the investigators were able to determine not only age, race, and sex, but also trauma sustained to the head and left arm at the time of death. This case highlights the importance and application of clinical radiography in a legal context. PMID- 2585284 TI - Os subcalcaneum. AB - An 11-year-old female presented with a history of pain in the left heel. Radiologic studies of both feet displayed a bony mass unilaterally. This bony mass had been identified radiologically as being separate from the posterior portion of the calcaneus. Clinically, the os subcalcaneum displayed a syndesmotic attachment to the calcaneus. Removal of the ossicle rendered the patient aysmptomatic. PMID- 2585285 TI - Acral lentiginous malignant melanoma. PMID- 2585286 TI - Intracisternal naloxone and cardiac nerve blockade prevent vasodilatation during simulated haemorrhage in awake rabbits. AB - 1. Acute haemorrhage was simulated in five unanaesthetized rabbits, by inflating a cuff on the inferior vena cava so that cardiac output fell by 8.3% of its resting level per minute. Simulated haemorrhage was performed after sham treatment, after graded doses of intravenous and intracisternal naloxone, and after cardiac nerve blockade with intrapericardial procaine. 2. After sham treatment, the haemodynamic response to simulated haemorrhage was biphasic. During the first phase, systemic vascular conductance fell steadily, heart rate rose steadily, and arterial pressure fell only slightly. A second decompensatory phase began abruptly when cardiac output had fallen to approximately 55% of its resting level. Vascular conductance rose steeply, heart rate fell slowly, and arterial pressure fell precipitately. 3. Treatment with naloxone (intravenous, 0.04-0.4 mg kg-1; intracisternal, 0.2-2 micrograms kg-1) did not affect either phase of the haemodynamic response to simulated haemorrhage. 4. After treatment with larger doses of naloxone (intravenous, 4-8 mg kg-1; intracisternal, 4-69 micrograms kg-1), the first phase was unaffected, but the second phase no longer occurred. Throughout simulated haemorrhage, systemic vascular conductance fell steadily, heart rate rose, and arterial pressure was well maintained. The dose of intracisternal naloxone which prevented the second phase was 90-900 times less than the corresponding intravenous dose. The second phase was also prevented by cardiac nerve blockade. 5. We conclude that an endogenous opiate mechanism is responsible for the haemodynamic decompensation that occurs when cardiac output falls to a critical level. The mechanism is located within the central nervous system. It is triggered by a signal from the heart. PMID- 2585287 TI - Excitatory synaptic responses in turtle cerebellar Purkinje cells. AB - 1. Climbing fibre responses (CFRs) and parallel fibre responses (PFRs) in Purkinje cells have been analysed in intracellular recordings obtained at various levels from cell body to terminal dendrites in the turtle cerebellum in vitro. 2. With increasing stimulus intensity, the PFR recorded in distal dendrites displayed an early regenerative component which was graded at rest and at hyperpolarized membrane potentials, but was all-or-none at depolarized membrane potentials. 3. The all-or-none component had the same characteristics as Ca2+ spikes triggered by passing depolarizing current through the recording electrode. 4. The repolarizing phase of the PFR had a fast component enhanced by depolarization and diminished by hyperpolarization. 5. In the mid-molecular layer the PFR also included a plateau component which was increasingly prolonged by depolarization and abolished by hyperpolarization. 6. CFRs recorded in the soma had a plateau component, prolonged by local depolarization and abolished by local hyperpolarization. 7. The CFR in distal dendrites included a regenerative component. In some cells this component appeared in an all-or-none manner with local depolarization. In other cells it was smoothly graded with local polarization. 8. In mid-molecular records the CFR was prolonged by local depolarization and presumably electrotonically affected by the configuration of the response more distally and proximally in the cell. 9. It is concluded that excitatory synaptic responses in Purkinje cells include a regenerative Ca2+ mediated spike component in the spiny dendrites and a plateau component located in the proximal dendrites and/or the cell body. It is shown that both responses are modulated in configuration by the local membrane potential. In the spiny dendrites activation and inactivation of the transient hyperpolarizing potential appear to govern the Ca2+ influx during the CFR. PMID- 2585288 TI - Pulmonary glucose transport in the fetal sheep. AB - 1. In the chronically catheterized sheep fetus between 122 and 143 days gestation the concentration of D-glucose in lung liquid was very low (usually less than 0.01 mM, the lower limit of detection of the analytical method) whereas the mean plasma concentration was 0.19 mM (S.E.M. 0.4, n = 13). 2. When the lung liquid concentration of D-glucose was raised to 1.67-5.00 mM, rapid uptake was observed until the concentration had fallen to its preceding low level. The uptake showed saturation kinetics (Vmax = 2.29-8.78 mumol/min, increasing with gestation; mean Km = 0.14 +/- 0.02 mM, n = 11, no change with gestation). This active uptake of glucose was blocked by phloridzin (10(-4) M). It was associated with a decrease in lung liquid secretion rate from which a change in net sodium flux could be inferred of an order suggesting one-to-one glucose-sodium co-transport. 3. Radiolabelled 3-O-methyl-D-glucose (3-O-meG) - a monosaccharide which is transported but not metabolized - was taken up rapidly from lung liquid and this rapid uptake was inhibited by D-glucose with 50% inhibition at 0.35 mM (+/- 0.08, n = 9). It was also inhibited by phloridzin (10(-4) M). 4. Radiolabelled 2-deoxy D-glucose - a monosaccharide which is not a substrate for sodium-coupled transport - was taken up only very slowly from lung liquid; the rate of uptake was appropriate for passive diffusional transport and it was unaffected by the addition of D-glucose or phloridzin to lung liquid. 5. Intravenous infusion of D glucose caused no detectable increase in the concentration of glucose in lung liquid unless phloridzin was added, when a slow increase was observed. 6. In two experiments with active transport blocked by phloridzin in lung liquid (10(-4) M), the rate of entry of labelled 3-O-meG from plasma to lung liquid was measured during intravenous infusion of this tracer for 29 and 23 h. The rates of entry were similar to the rate of efflux of the tracer from lung liquid when uptake was blocked by phloridzin or D-glucose, and similar to the rate expected for a metabolically inert tracer (i.e. it was some two orders of magnitude less than efflux from lung liquid in the absence of an inhibitor).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2585289 TI - Synaptic control of excitability in turtle cerebellar Purkinje cells. AB - 1. In turtle Purkinje cells in vitro successive climbing fibre responses (CFRs) gradually induced a hyperpolarization that persisted with maintained stimulation and decayed over minutes after climbing fibre stimulation was terminated. 2. The rate of development and the amplitude of this long-lasting hyperpolarization (LHP) increased with the frequency of CFRs. 3. The LHP was also induced by Ca2+ spikes evoked by current injection but not by Na+ spikes. The LHP was blocked by Co2+ but not by tetrodotoxin and could not be explained solely by an increased K+ conductance. 4. Depolarizing current during a train of CFRs enhanced the regenerative component of CFRs and promoted the LHP. Hyperpolarizing current during the stimulus train reduced the regenerative component of CFRs and attenuated the resulting LHP. 5. In the range of membrane potentials attained at different levels of climbing fibre activity the regenerative component of CFRs varied from being dominant at very low stimulus frequency (0.1 s-1) to being inconspicuous at high stimulus frequency (10 s-1). 6. It is concluded that successive CFRs induce a Ca2+-dependent, long-lasting hyperpolarization. The magnitude of the hyperpolarization is regulated by the rate of CFRs and by the voltage- and frequency-dependent configuration of each individual CFR. 7. The active, non-synaptic properties of turtle Purkinje cells make the Ca2+ influx during climbing fibre responses prone to regulation by on-going synaptic activity and by the after-effects of synaptic activity on a time scale of minutes. We suggest that this arrangement may enhance the capacity and complexity of spatial and temporal synaptic integration in Purkinje cells. PMID- 2585290 TI - An after-hyperpolarization of medium duration in rat hippocampal pyramidal cells. AB - 1. In hippocampal pyramidal cells, action potentials are followed by three after hyperpolarizations (AHPs): a fast AHP (fAHP) lasting 2-5 ms, a medium AHP (mAHP) lasting 50-100 ms, and a slow AHP (sAHP) lasting more than 1 s. The mechanism underlying the mAHP was studied in CA1 cells (n = 46) in rat hippocampal slices, using injection of depolarizing current to elicit discharge. 2. The current underlying the mAHP was studied by single-electrode voltage clamp in two ways. Either the voltage clamp was activated following a burst of spikes, thus recording the early tail current underlying the mAHP (hybrid clamp), or, after blocking the spikes with tetrodotoxin, the early tail current following a depolarizing voltage clamp command (to -20 to -45 mV for 100-400 ms) was measured. In both cases, the early tail current (measured at -60 mV) showed the following characteristics: (a) it decayed exponentially with a time constant of about 50 ms; (b) it was substantially reduced by the muscarinic agonist carbachol (40-50 microM); (c) it was moderately reduced (by 20% or less) by Ca2+-free medium and Ca2+ channel blockers (Cd2+, Mn2+), which abolished the fAHP and the sAHP; (d) it was partly blocked by tetraethylammonium (TEA, 1-10 mM) both before and during Ca2+ channel blockade; (e) it was resistant to noradrenaline (5-10 microM), which blocked the sAHP, and to apamin (100 nM). 3. The mAHP itself, recorded under current clamp, showed properties corresponding to those of the early tail current. 4. Unlike the current underlying the sAHP, which was reduced and reversed by hyperpolarization, the early tail current appeared to be reduced only at potentials down to -80 mV, and to increase at more negative potentials. The early tail current and mAHP-like undershoot at hyperpolarized potentials was blocked by external Cs+, but not by carbachol, in contrast to the early tail current and mAHP at -60 mV. 5. It was concluded that two currents contribute to the mAHP: IM (a voltage-gated muscarine-sensitive K+ current) and IC (a Ca2+ dependent TEA-sensitive K+ current). TEA reduced both the IM (5 mM) and the IC (1 mM) component of the mAHP. When the cell is hyperpolarized, a third current, IQ (a Ca+-sensitive mixed Na+-K+ inward current activated by hyperpolarization), masks the reversal of the mAHP by causing a depolarizing sag which resembles the decay of the mAHP. PMID- 2585291 TI - Multiple-site optical monitoring of neural activity evoked by vagus nerve stimulation in the embryonic chick brain stem. AB - 1. Electrical activity in the embryonic chick brain stem has been monitored optically. The vagus-brain stem preparations isolated from 7-day-old chick embryos were stained with voltage-sensitive merocyanine-rhodanine dyes. 2. Voltage-related optical absorption signals evoked by vagus nerve stimulation with depolarizing and hyperpolarizing pulses using a suction electrode were recorded simultaneously from 127 adjacent loci in the brain stem using a 12 x 12-element photodiode array. 3. The optical signals evoked by the stimulation appeared to be concentrated longitudinally in the central region and in the lateral region, both on the stimulated side of the brain stem, and they did not spread to the opposite side. In addition, the evoked optical responses were detected from small areas on the dorsal surface of the stimulated side, in experiments using transverse slices of brain stem. 4. The optical action potential signals evoked by the brief depolarizing stimulus were conducted slowly and were blocked completely by tetrodotoxin. With relatively long-duration depolarizing and hyperpolarizing stimulations, electrotonic responses were recorded. 5. When 2 microA/2 ms hyperpolarizing pulse stimulations were applied, anode-break excitation signals were detected, and these signals were also blocked by tetrodotoxin. 6. On the basis of the data obtained from these experiments, we constructed maps of the electrical response area and demonstrated the spatial pattern of the vagus dorsal nucleus in the 7-day-old embryonic chick brain stem. PMID- 2585292 TI - Endogenous histamine excites neurones in the guinea-pig superior cervical ganglion in vitro. AB - 1. Intracellular recordings were obtained from neurones in the guinea-pig superior cervical ganglion (SCG) in vitro to study the electrophysiological effects of endogenously released histamine. 2. Guinea-pigs were actively sensitized to the specific antigen, ovalbumin. SCG removed from these animals rapidly released a significant proportion of their endogenous histamine stores into the extracellular space upon exposure to the sensitizing antigen. Several observations indicated that the released histamine was derived from ganglionic mast cells. 3. The electrophysiological effects produced by antigen challenge in a neurone mimicked qualitatively and quantitatively those effects produced by exogenously applied histamine in the same neurone. Under current clamp the membrane effects of antigen and histamine included a transient depolarization, an increase in input resistance and transient blockade of a long-duration component of the spike after-hyperpolarization. In voltage clamp histamine and antigen produced an inward current and decreased membrane conductance. 4. Histamine H1, but not H2 or H3 receptor antagonists prevented the membrane depolarization to both histamine and antigen treatments. 5. These convergent biochemical, physiological and pharmacological data demonstrate that a sufficient quantity of endogenous histamine is released by an antigenic stimulus in SCG from sensitized guinea-pigs to affect specific electrophysiological characteristics of neurones. Histamine may thus be involved in mediating interactions between the mammalian immune system and the peripheral sympathetic nervous system. PMID- 2585293 TI - Cardiovascular responses to brief static contractions in man with topical nervous blockade. AB - 1. We tested the hypothesis that afferent nerves from working muscles are important in determining the heart rate and blood pressure responses to brief maximal static exercise. 2. In twenty human subjects, the heart rate and arterial blood pressure responses to a brief maximal voluntary handgrip were studied before and after axillary nerve anaesthesia or to maximal one-leg knee extension before and after epidural anaesthesia at L3-L4. Maximal knee extension could not be accomplished without performing a 'Valsalva-like' manoeuvre, but during handgrip it was possible to avoid the use of muscles other than those directly involved in the contraction. Heart rate and blood pressure were also monitored during a Valsalva manoeuvre of similar duration to the maximal voluntary contractions (4 s). 3. During handgrip with normal breathing, axillary nerve anaesthesia reduced the heart rate response but had no effect on the blood pressure response. 4. During a Valsalva manoeuvre, blood pressure increased but heart rate remained stable as long as expiratory pressure was maintained. During one-leg knee extension, epidural anaesthesia reduced the blood pressure response; however, the reduction in blood pressure was probably due to a reduction in the simultaneously performed 'Valsalva-like' manoeuvre. 5. The results of this study suggest that afferent input from the working muscles is of importance for the heart rate responses to brief static muscle contractions. That such influence may be important for the blood pressure response remains unproven. PMID- 2585294 TI - The effect of distension of the urinary bladder on activity in efferent renal fibres in anaesthetized dogs. AB - 1. To test whether distension of the urinary bladder causes a consistent change in activity in efferent renal nerve fibres, bladder distension was performed in anaesthetized dogs. The carotid sinuses were vascularly isolated and perfused with blood at constant flow. Both ureters were cannulated and the urinary bladder was distended with warm Ringer solution at a steady intravesical pressure. 2. In a first series of experiments all twenty-six renal nerve fibres in eleven dogs which responded to changes in carotid sinus pressure and changes in the nature of the blood perfusing the carotid sinuses also responded to distension of the bladder. 3. In a second series of experiments, graded bladder distension over a range of pressure of 0-9.2 kPa led to a graded increase in activity in thirteen efferent renal fibres in six dogs. The magnitude of the renal nerve response was greater at low than at high carotid sinus pressure. Over a range of carotid sinus pressure of 9-30 kPa, the greatest renal nerve activity was obtained at the lower end of this range in the presence of bladder distension. 4. Thus distension of the urinary bladder resulted in the response of a consistent increase in efferent renal nerve activity, which could be graded according to intravesical pressure. The magnitude of the responses to bladder distension was affected by carotid sinus pressure. PMID- 2585295 TI - Duodenal bulb control of the flow rate of digesta in the fasted and fed dog. AB - 1. Continuous measurement of the flow of digesta near the pylorus, and 5 cm aborally, was assessed in the conscious dog using a chronically implanted flowmeter. The patterns of flow were related to motor activity of the gastroduodenal junction. 2. Electromagnetic measurement of the flow was calibrated in vitro by means of a pulsatile pump. Validation was obtained in vivo by direct evaluation of the amount of chyme collected from an open duodenal cannula and indirectly by a dye-dilution technique. 3. After a 12 h fast, only small amounts of gastric contents were delivered into the duodenum. This transfer occurred during periods of irregular motor activity recorded along the gastroduodenal junction, which occupied less than 25% of the recording time. The patterns of flow near the pylorus and beyond the duodenal bulb were correlated to antral and duodenal contractions respectively. 4. After a meal, gastric emptying occurred intermittently and was related to enhanced antral motor activity beyond the duodenal bulb; digesta flowed in clusters of gushes which were related to the duodenal contractions. 5. It is concluded that the mechanical role of the duodenal bulb is to change the intermittent juxtapyloric flow of digesta into a uniform flow at the duodenal level. PMID- 2585296 TI - Properties of calcium stores and transient outward currents in single smooth muscle cells of rabbit intestine. AB - 1. Single dispersed cells obtained by collagenase treatment of longitudinal muscle of rabbit small intestine were voltage clamped with low-resistance patch pipettes and membrane current was measured. 2. In cells held at -20 or -30 mV, a discharge of spontaneous transient outward currents (STOCs) was usually seen; these are believed to represent the sporadic release of calcium from storage sites in the cell in relation to TEA-sensitive, 4 AP-resistant, calcium-activated potassium channels. 3. Caffeine (20 mM) externally applied, accelerated and then abolished STOCs; carbachol (0.1 mM) had similar effects; the initial burst of STOCs was often carried on a large, temporary, outward current which could occur alone. This was suggested to be caused by the rapid release of stored calcium in relation to calcium-activated potassium channels. 4. If STOCs were abolished by caffeine (or carbachol) then carbachol (or caffeine) did not evoke outward current indicating that these drugs act on the same calcium store but by different pathways. Inclusion of ryanodine (10(-8)-10(-4) M) in the patch pipette abolished STOCs soon after establishing whole-cell recording mode; afterwards, outward current to caffeine or to carbachol could not be evoked. 5. STOCs were quickly abolished in cells patched with pipettes filled with GTP gamma S (0.1-1 mM) or Gpp(NH)p (0.1-1 mM) but were large or normal in size in cells where GDP beta S (0.1-1 mM) was included in the pipette. GTP gamma S or Gpp(NH)p in the cell abolished outward current to caffeine or to carbachol, but had no effect on calcium-activated potassium channel activity in isolated patches or on a TEA sensitive, 4-AP-resistant, outward potassium current evoked in single cells by stepping positively from a -20 mV holding potential. These results suggest that the effect of guanine nucleotide analogues are on the calcium store rather than on calcium-activated potassium channels. 6. The effects of GTP gamma S or Gpp(NH)p could be explained if they depleted calcium stores via a G-protein mechanism; this effect may involve activation of phospholipase C enzyme (PLC) and D-myo-inositol 1,4,5-trisphosphate (IP3) production as well as a direct effect on stores. However a separate G-protein-independent pathway of activation of PLC by muscarinic receptor activation may exist as calcium release by carbachol was large or normal in cells filled with GDP beta S. PMID- 2585297 TI - Selective recruitment of high-threshold human motor units during voluntary isotonic lengthening of active muscles. AB - 1. We have investigated the possibility that voluntary muscle lengthening contractions can be performed by selective recruitment of fast-twitch motor units, accompanied by derecruitment of slow-twitch motor units. 2. The behaviour of motor units in soleus, gastrocnemius lateralis and gastrocnemius medialis muscles was studied during (a) controlled isotonic plantar flexion against a constant load (shortening contraction, S), maintained plantar flexion, or dorsal flexion resisting the load and gradually yielding to it (lengthening contraction, L), (b) isometric increasing or decreasing plantar torque accomplished by graded contraction or relaxation of the triceps surae muscles, (c) isometric or isotonic ballistic contractions, and (d) periodic, quasi-sinusoidal isotonic contractions at different velocities. The above tasks were performed under visual control of foot position, without activation of antagonist muscles. The motor units discharging during foot rotation were grouped on the basis of the phase(s) during which they were active as S, S + L and L. The units were also characterized according to both the level of isometric ramp plantar torque at which they were first recruited and the amplitude of their action potential. 3. S units were never active during dorsal flexion; some of them were active during the sustained contraction between plantar and dorsal flexion. Most S + L units were active also during the maintenance phase and were slowly derecruited during lengthening; their behaviour during foot rotations was similar to that during isometric contractions or relaxations. L units were never active during either plantar or maintained flexion, but discharged during lengthening contraction in a given range of rotation velocities; the velocity of lengthening consistently influenced the firing frequency of these units. Such dependence on velocity was not observed in S + L units. 4. A correlation was found between the amplitude of the action potential and the threshold torque of recruitment among all the units. In addition, the amplitudes of both the action potential and the threshold torque were higher in the case of L units than in the case of S and S + L units. Most L units could be voluntarily recruited only in the case of ballistic isometric or isotonic contraction. 5. Occasionally, L units were directly activated by electrical stimulation of motor fibres and their conduction velocity was in the higher range for alpha-axons. In contrast, nerve stimulation could induce a reflex activation of S and S + L units.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2585298 TI - Maximum tension and force-velocity properties of fatigued, single Xenopus muscle fibres studied by caffeine and high K+. AB - 1. The importance of reduced maximum force-generating capacity in the development of skeletal muscle fatigue has been studied using potassium and caffeine contractures as tools. 2. Single, intact fibres isolated from the lumbrical and iliofibularis muscles of Xenopus were fatigued by repeated tetanic stimulations until they produced close to 40% of the original tetanic tension (P0). Using this stimulation scheme three major types of fibres can be distinguished: easily fatigued (type 1), fatigue resistant (type 2), and very fatigue-resistant (type 3) fibres (Westerblad & Lannergren, 1986). 3. When activated by 8-15 mM-caffeine Ringer solutions fatigued fibres of all three types developed tensions similar to those of controls (81.0 +/- 6.6 vs. 83.9 +/- 4.2% of P0, respectively; means +/- S.D.). 4. Tension output also increased markedly when fatigued fibres were depolarized by 190 mM-K+ solution. The tension produced was in this case fibre type dependent: 71.4 +/- 6.6, 81.3 +/- 2.5 and 95.0 +/- 4.4% of P0 in fibre types 1, 2 and 3, respectively. 5. Force-velocity measurements were performed during caffeine contractures in fatigued iliofibularis fibres (types 1 and 2) to obtain more information about the functional state of cross-bridges. 6. In fatigued type 1 fibres the shortening velocity was reduced to about 25% of that in controls, while it was not significantly depressed in type 2 fibres. 7. It is concluded that cross-bridges of fatigued fibres can produce nearly full tension, but they may work at a much slower rate in this state. 8. Fibre types 1 and 2 mostly display a long-lasting, reversible state of severely depressed tension production during the recovery period, which has been named post-contractile depression, PCD (Westerblad & Lannergren, 1986). Fibres tested in this state generated full caffeine-activated tension and the shortening velocity was not significantly reduced. The tension output during K+ contractures was, however, markedly depressed (12.4 +/- 4.1% of P0). 9. In conclusion, cross-bridges are able to produce close to full tension during PCD as well as in the fatigued state if they are fully activated. The form of functional impairment seems, however, not to be the same in the two cases. PMID- 2585299 TI - Muscle filament spacing and short-term heavy-resistance exercise in humans. AB - 1. Six weeks of a dynamic heavy-resistance training of the quadriceps muscle in healthy young men resulted in a continuous increase in muscle strength, in an increase in muscle cross-sectional area (significant only in the second half of the training period) and in an increase in radiological density of the muscle tissue of 3.1% (2P less than 0.001) in the first three weeks and 1.6% (2P less than 0.01) in the second three weeks. 2. The linear distance between myosin filaments (38.7 +/- 0.3 nm before, 38.7 +/- 0.4 nm after training; mean +/- S.E.M.) as well as the ratio of actin to myosin filaments (3.94 +/- 0.03 before, 3.86 +/- 0.06 after training) did not change with training. 3. These results refute the concept that the increases in muscle strength or radiological density during short-term heavy-resistance training are caused by changes in myofilament spacing. PMID- 2585301 TI - The intrinsic intracellular H+ buffering power of snail neurones. AB - 1. We measured intracellular pH (pHi) in snail neurones using pH-sensitive glass microelectrodes. We then calculated the intracellular buffering power (beta i) from the pHi changes associated with the influx or efflux of a variety of weak acids or bases. 2. The weak acid anions butyrate and propionate (20 mM) gave similar values for beta i but those measured using 20 mM-acetate were on average twice as great. 3. Although solutions were nominally CO2-free, blockage of pHi regulation with SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid) increased the sizes of the pHi changes upon weak acid addition and removal. The corresponding measured values of beta i were on average 26% lower with SITS than without. 4. With pHi regulation blocked, the use of 2.7% CO2 to measure beta i gave beta i values similar to those measured with butyrate or propionate. These values were about 50% less than those previously measured in snail neurones using CO2. 5. beta i values calculated from the pHi changes due to the removal of 5 mM of the weak bases trimethylamine, procaine and NH4Cl were all similar and comparable to those measured using butyrate or propionate. Removing the influence of pHi regulation on the undershoots after NH4Cl removal was found to decrease the apparent measured values of beta i by 10%. 6. Combining all the data (except the values obtained using CO2 and acetate), and adjusting for the errors due to pHi regulation reducing the sizes of the pHi changes, we found that the mean value for beta i was 10.4 +/- 0.6 mM (+/- S.E.M.) at a mean pHi of 7.36 +/- 0.05. 7. We also investigated the relationship between beta i and pHi using ionophoretic acid injection. By means of step-wise injections, with pHi regulation blocked, we found that at normal pHi levels beta i remained relatively constant. However, at a pHi of less than about 6.8 beta i increased with decreasing pHi. PMID- 2585300 TI - Cable properties of cat spinal motoneurones measured by combining voltage clamp, current clamp and intracellular staining. AB - 1. Spinal alpha-motoneurones were injected with horseradish peroxidase after measuring their voltage response to a brief current pulse and their current response to a small voltage step. 2. The morphology of each motoneurone was reconstructed from serial sections. The diameters and lengths of dendritic segments were used to build a compartmental model of each neurone's electrotonic structure. The specific resistivity of the membrane (Rm) was assumed to be constant throughout the dendrites, but it was lowered for the somatic membrane by the introduction of a somatic shunt resistance. 3. The specific resistances of the somatic and dendritic membrane were adjusted in the compartmental model until the responses of the model to the same current and voltage steps as those used in the experiment gave the best fits to the recorded transients. Satisfactory fits were obtained for six out of seven motoneurones. Dendritic Rm varied from 7 to 35 k omega cm2 and somatic Rm varied from 100 to 420 omega cm2. The dendritic Rm was 100-300 times the somatic Rm for different neurones. 4. The calculated dendritic Rm was used to determine the geometric profile of the equivalent dendritic cable. This was found to be an approximately uniform cylinder for about 0.5 lambda and thereafter to taper rapidly to a final termination at 2-3 lambda from the soma. 5. The results indicate that motoneurone dendrites are more electrically compact than was hitherto believed. The different Rm values for somatic and dendritic membrane, and the tapering of the dendritic cable, means that the cable model developed by Rall (1959, 1964) must be revised to take account of these spatial and electrical non-uniformities. PMID- 2585302 TI - Brushite in the pulp of primary molars. AB - This study was undertaken to investigate the mineral phase of spherulitic calcifications discovered in the pulpous mesenchyme of human primary molars by microradiography. Analytical scanning electron microscopy and x-ray diffraction disclosed that well-crystallized brushite is the major compound of the spherulites. The mechanism leading to the crystallization of brushite is far from well understood. Histologically, on decalcified sections, inflammatory cells and capillaries can be seen trapped in the spherulites. In the light of these findings, it could be suggested that metabolic conditions may promote the crystallization of brushite in the pulp of primary molars. PMID- 2585303 TI - Variant sublines with different metastatic potentials selected in nude mice from human oral squamous cell carcinomas. AB - Variant sublines LMF3, LMF4 and LMF5 with high metastatic potential were established from a human oral squamous carcinoma cell line HSC-3. These sublines metastasized to the draining lymph nodes after subcutaneous inoculation into nude mice. They were obtained by sequential selection in vivo from the parent HSC-3. At each step, the cells which metastasized to lymph nodes were cultured and reinoculated into nude mice. Two other cell lines HSC-2 and HSC-4 were also established from other patients, that had neither invasive nor metastatic potential. Biologic properties were compared among high metastatic, low metastatic and non-metastatic cells. Metastatic cells grew rapidly and invaded into surrounding tissues at the inoculated site. The incidence of pulmonary colonization after intravenous injection of tumor cells was high in selected variants. Metastatic cells formed diffuse colonies in type I collagen matrix and had a higher tendency to adhere to type IV collagen network. PMID- 2585304 TI - Acinic cell carcinoma of salivary glands: 16 cases with clinicopathologic correlation. AB - Sixteen cases of acinic cell carcinoma (ACC) of salivary glands were studied and their different clinicopathologic aspects were analysed. ACC occurred more frequently in the 5th and 6th decades of life, and was seen exclusively in major salivary glands. The main complaint of the patients was the presence of a mass, and the majority of the tumors were Stage III and IV when first seen in our institution. The tumors were divided into three histologic grades based on cellular pleomorphism, mitotic activity, and necrosis. This study showed correlation between prognosis and grading. Other important factors in the prognosis were the type of treatment and the duration of symptoms. Surgical resection with free margins is the treatment of choice. PMID- 2585305 TI - Low prevalence of oral mucosal lesions in HIV-1 seropositive African women. AB - In Nairobi (Kenya) 334 women prostitutes of whom 80.5% were HIV-1 positive, were examined for oral mucosal lesions; 15.6% of seropositive, and 4.6% of seronegative, women had oral mucosal lesions, predominantly oral candidiasis. In the seropositives, 8.6% had erythematous, 1.1% had hyperplastic candidiasis, and 0.4% had hairly leukoplakia as the only oral lesions; 0.4% had a combination of erythematous and hyperplastic candidiasis, and 1.5% had combinations of pseudomembranous and erythematous candidiasis in the presence of hairly leukoplakia. Of the 211 seropositive women for whom we knew the first date on which a positive serologic test was obtained, the likelihood of developing an oral mucosal lesion was found to be dependent on the duration of seropositivity. The low incidence of oral mucosal lesions in this population may be due to the relatively recent acquisition of HIV-1 infection. PMID- 2585307 TI - The law and your profession. PMID- 2585306 TI - Verapamil-induced gingival overgrowth: a clinical, histologic, and biochemic approach. AB - Verapamil-induced overgrowth was most prominent in the anterior regions and interproximal areas associated with plaque retention. Despite periodontal therapy, overgrowths recurred 1 month after gingivectomy. Discontinuation of the drug resulted in regression of the overgrowths. Histologic findings showed inflamed connective tissue covered by an acanthotic, thickened oral epithelium with long rete pegs containing dyskeratotic pearls. The proliferation rate and protein and collagen production of fibroblasts from the overgrowth sites were markedly lower than in the control cells cultured from healthy gingiva. Incubation of fibroblasts in the presence of verapamil reduced protein and collagen synthesis. PMID- 2585308 TI - The nurse's role in informed consent. PMID- 2585309 TI - Writing for the nursing press. PMID- 2585310 TI - The use of vascularized bone grafts in osseointegration. A clinical report. AB - This clinical report presented the concept of a vascularized bone graft for mandibular reconstruction coupled with osseointegration to achieve a superior rehabilitative result. The potential use of these two modalities enables the reconstructive team to restore functional and esthetic levels previously not possible after radical surgery. The application of this technique is not limited to cancer surgery patients, but may be advisable for patients requiring reconstruction of mandibular discontinuity. PMID- 2585311 TI - Clinical implications of resilient denture lining material research. Part I: Flexibility and elasticity. AB - The clinical use of resilient denture liners is based on their flexibility and elasticity. The nine commercial resilient denture liners measured were less flexible during and after simulated chewing and clenching test sequences. The elasticity of the intraoral-cure liners reached maximal values at 24 hours. Although interpretations require caution, the results imply that the dentist should (1) use maximum liner thickness in the denture base when conditioning abused supporting tissues because of the material's tendency to stiffen under function, and (2) leave a functional impression in the mouth for at least 24 hours before pouring the cast. PMID- 2585312 TI - Vital root retention: a clinical procedure. AB - Retention of vital roots retards the resorption of residual alveolar ridges under complete dentures. It also eliminates the patient's responsibility of maintaining the periodontal health of overdenture abutments. The procedure involves (1) preparing the teeth to be retained from a periodontal standpoint to reduce the possibility of contamination of the surgical site, (2) removing hopeless teeth, (3) sectioning and contouring the teeth so that the retained roots are contiguous with the crestal bone, (4) preparing and suturing labial and lingual flaps to cover the prepared roots and maintain proper vestibular depth, and (5) placing an immediate denture relined with tissue-conditioning material. PMID- 2585313 TI - Quantitative and subjective analysis of temporomandibular joint radiographs. AB - The lateral oblique transcranial radiograph of the temporomandibular joint is commonly used in dentistry. Changes in horizontal angulation of the x-ray beam can produce changes in radiographic condylar position. This study used quantitative and subjective methods to assess and rank changes in radiographic condylar position as a function of known horizontal x-ray beam changes. Six dry skulls were positioned in a craniostat device where known angulations could be measured. Nine sequential transcranial temporomandibular joint radiographs were made of each joint and five of these 12 sets were randomly selected for analyses. The quantitative method involved film digitization, computer calculations, and expressed condylar position as a ratio between posterior and anterior joint space distributions. Eight observers viewed the same films and ranked radiographic condylar position from anterior to posterior. The two methods agreed with known rankings 81.8% of the time. Subjective rankings were more variable than quantitative rankings. Intraobserver differences were insignificant and the observers were consistent among themselves as a group. PMID- 2585314 TI - A comparative strength study of metal ceramic and all-ceramic esthetic materials: modulus of rupture. AB - The modulus of rupture for three metal ceramics and five all-ceramic substructures with and without veneer porcelain was compared. Support of the veneer porcelain was directly related to the modulus of elasticity and not to the strength of the substructure material. The higher the modulus of elasticity, the greater was the strength of the veneered restoration. For each 1 x 10(6) increase in the modulus there was a corresponding 1040 psi increase in strength. The veneered all-ceramics had 45% to 70% of the strength of the metal ceramic restorations. The veneered nonprecious and gold-palladium metal ceramic test bars were significantly stronger than any veneered all-ceramic material. PMID- 2585315 TI - Skeletal osteopenia and residual ridge resorption. PMID- 2585316 TI - Tannic acid for smear layer removal: pilot study with scanning electron microscope. PMID- 2585317 TI - Use of mouthguards during tooth preparation for patients with extreme tooth sensitivity. PMID- 2585318 TI - Temperature rise in the pulp chamber during fabrication of provisional crowns. AB - This study measured and compared thermal changes in the pulp chamber during the fabrication of provisional crowns by direct method using various brands of autopolymerizing resin systems. The effect of curing the crowns in condensation and addition-reaction silicone putty matrices was also evaluated. The results suggested that the amount of heat transferred in the pulp chamber during the curing of resins may be damaging to the dental pulp and odontoblasts. Curing provisional resin crowns in either condensation or addition silicone putty impressions significantly reduced the temperature rise in the pulp chamber. PMID- 2585319 TI - A radiologic method for determining the thickness of the hard crown tissues. AB - This study describes a radiologic method that provides a reliable evaluation of the thickness of the hard crown tissues of the tooth scheduled for prosthetic and conservative preparation. The first stage consisted of calculating the discrepancy between the actual dimensions of the specimen under examination and the dimensions of the same specimen as measured and radiographed. Some coefficients of distortion were calculated for the distance(s) more usually involved clinically. Radiographs were made by using the "paralleling" technique. In the second stage, radiographs were made of 83 extracted teeth (22 incisors, 12 canines, and 51 premolars). On the resulting radiographs some prefixed distances were measured. Finally, to gain an anatomic comparison of the values obtained radiologically, 24 of the previously radiographed teeth were sectioned along the sagittal plane at the diameter, and measurements were made and compared with the radiologic data to which the correction coefficients had been applied. PMID- 2585320 TI - Severe vertical overlap: a modified method of treatment. AB - Severe vertical overlap may predispose the patient to abnormal function, improper mastication, excessive stress, and functional problems such as bruxing, clenching, and craniomandibular disorders. This report describes the establishment of a new occlusal relationship by using the potential of posterior tooth eruption with the Hawley bite plane or the canine platform method. It was used in patients with a full complement of teeth or with some missing teeth. Patients treated by either the Hawley bite plane or the canine platform demonstrate a stable and long-lasting new occlusal relationship. The method described is efficient, inexpensive, and convenient to the patient. PMID- 2585321 TI - Prevalence of the 'combination syndrome' among denture patients. AB - The prevalence of symptoms associated with "combination syndrome" were documented in 150 maxillary complete denture wearers. The five alveolar ridge changes that are most consequential to denture wearing and most difficult to correct surgically were found in 7% of the population studied. However, these changes were found in 24% of patients who have natural mandibular anterior teeth opposing complete maxillary dentures. This rate did not differ significantly between patients who do and do not wear a mandibular removable partial denture. PMID- 2585322 TI - Ten-year study of trends in removable prosthodontic service. AB - To gain an overview of where the field of removable prosthodontics may be heading, an ex post facto research project was completed that randomly sampled the charts of patients screened for removable prosthodontics during 1977-1979 and 1985-1987. The information showed that, overall, the number of complete dentures was declining whereas the number of removable partial dentures was increasing. The fastest growing prosthodontic service was the combination of the maxillary complete denture opposing the mandibular removable partial denture. Curriculum changes based on the results of the research were made. PMID- 2585323 TI - A comparison of self-assessed satisfaction among wearers of dentures, hearing aids, and eyeglasses. AB - Patient assessment of dental prostheses, hearing aids, and eyeglasses can provide valuable data regarding adaptability of geriatric patients. This article describes a cross-modality evaluation of patient satisfaction with dental, hearing, and vision prostheses. Three hundred ninety-one subjects with recently placed prostheses were evaluated for self-assessed satisfaction and other related information. Patient satisfaction was compared with, age, type of prosthesis, and level of impairment. No statistical evidence of an age-related dissatisfaction with prostheses was found. Significant differences in levels of satisfaction were noted between different types of prostheses. Irrespective of level of impairment, patients expressed greatest satisfaction with dental prostheses and least satisfaction with hearing aids. PMID- 2585324 TI - A technique for fabrication of a custom tracheostomy prosthesis. AB - A technique is described for using an endotracheal tube to make an impression of the intratracheal anatomy for fabrication of a custom-fitted tracheostomy prosthesis. PMID- 2585325 TI - The sleep apnea syndrome. Part I: Diagnosis. AB - Part I of this two-part article presents a review of the symptoms, pathophysiology, and diagnosis of the sleep apnea syndrome. The more common obstructive type is characterized by disturbed sleep and daytime hypersomnolence. Subjective signs and symptoms should be correlated with objective findings by way of polysomnography (sleep study) to confirm the diagnosis and determine the severity of obstructive sleep apnea. Electrocardiographic monitoring during polysomnography has revealed potentially life-threatening arrhythmias during sleep. Differential diagnosis should include central sleep apnea and narcolepsy to avoid inappropriate therapy and worsening of symptoms. PMID- 2585326 TI - A mouth splint for severe burns of the head and neck. AB - An individual mouth splint device that applies continuous or intermittent pressure to stretch commissures and fibrotic muscles in patients treated for microstomia resulting from facial and neck burns is presented. After an individual lip tray is prepared, the method uses the impression and cast of the region of the lips to construct a pink acrylic resin splint. By using the device, split horizontally and activated with a Hyrx screw, an opening of 14 mm can be obtained within 2 weeks. The device is recommended as being easily constructed, inexpensive, almost painlessly inserted, and progressively activated. PMID- 2585327 TI - Proportionality of mean voltage of masseter muscle to maximum bite force applied for diagnosing temporomandibular joint disturbance syndrome. AB - Maximum bite force in the region of the right first maxillary molar and the corresponding mean voltage of the right masseter muscle of 29 patients suffering from temporomandibular joint dysfunction and 27 healthy controls were measured. In contrast with the controls, the maximum bite force of the patients was smaller (p less than 0.01), the mean voltage was nearly equal (p greater than 0.05), and the proportionality of the mean voltage to the maximum bite force of the patients was greater (p less than 0.01). These results tend to indicate that the masticatory muscles of patients with temporomandibular joint dysfunction are in a state of hyperactivity and tension. The proportionality method suggested in this article is more convenient and easier to apply than previously proposed methods that measure the slope of voltage/tension curves. It may, therefore, have clinical value in the diagnosis of patients with temporomandibular joint disorders. PMID- 2585328 TI - Relationships between mandibular and skeletal bone in an osteoporotic population. AB - This study attempted to determine relationships between bone mass in the mandible and skeletal bone mass in a group of 85 postmenopausal women with osteoporosis. Mandibular bone mass was determined by microdensitometry, cortical thickness at the gonion, the height of the alveolar ridge in subjects who were edentulous, and periodontal probings. Skeletal measures were made up of total body calcium, bone mass at the radius, and the two newer bone mass measures of dual photon and computed tomography of the vertebrae. The height of the edentulous ridge correlated with total body calcium and mandibular mass. Most of the edentulous patients had ridges that were extremely resorbed. Mandibular mass correlated with all skeletal measures. PMID- 2585329 TI - Removable prosthodontics research--quo vadis? AB - The need to improve removable prosthodontic treatment through research has not diminished. Most recent research reports in prosthodontics are in fixed prosthodontics, indicating a declining interest in removable prosthodontics. A survey of dental schools in the United States and Canada reveals that the financial support for research in removable prosthodontics is a mean of $42,500 per year. Present research is not directed toward solving the major problems in removable prosthodontics. The key to making progress in removable prosthodontic research is to interest capable trainees in securing the necessary basic science and clinical training. Adequate financial support is then needed to conduct the research. PMID- 2585330 TI - Deflation of the 'obstinate' Foley's urinary catheter balloon: a new technique. AB - We have successfully deflated "obstinate" Foley's urinary catheter balloons in 15 cases in the last six months with the help of a simple bedside procedure using an angiographic guide-wire. PMID- 2585331 TI - Nosocomial infections due to Acinetobacter calcoaceticus. AB - Fifty four isolates of Acinetobacter calcoaceticus were studied in a period of 6 months. Maximum isolates were from burns cases and environmental sampling from burns ward also grew the same organism, indicating their role as nosocomial pathogen. Acinetobacter may initially be mistaken for Neisseria species. As the organisms show multidrug resistance to commonly used antibiotics their correct identification is important. PMID- 2585332 TI - Serum immunoglobulins in viral hepatitis. AB - The serum levels of IgA, IgG and IgM were determined by single radial immuno diffusion technique in 104 male patients of acute viral hepatitis. HBsAg was detected by counterimmuno-electrophoresis (CIEP) and 51% were HBsAg + ve. IgA, IgG and IgM levels were found to be higher than normal levels. Mean IgA and IgG levels were same in HBsAg + ve and HBsAg--ve patients. Mean IgM levels were however, higher in HBsAg--ve patients. PMID- 2585333 TI - Prevalence of antibodies to aspergilli in bronchial asthmatics. AB - Sputum and bleed samples were analysed from 330 cases of bronchial asthmatics and 50 normal persons without features of bronchial asthma. The prevalence of aspergilli and antibodies to different Aspergillus species were detected using cultural methods and serological technique like agar gel double diffusion (DD), counter-immuno-electrophoresis (CIEP) and enzyme-linked immunosorbent assay (ELISA). Out of total 6.06% yielded Aspergillus species in sputum specimens repeatedly. Precipitins against Aspergillus species were detected in 7.88% of cases by DD and CIEP. ELISA test showed 20% of cases to be having antibodies to A. fumigatus. Allergic broncho-pulmonary aspergillosis can be detected in the early course of the disease in bronchial asthmatics using highly sensitive technique like ELISA. PMID- 2585334 TI - Immunoprofile of pulmonary tuberculosis-comparison with normal healthy controls. AB - The immunoprofile of 60 adult patients of pulmonary tuberculosis was studied and compared with 22 normal controls. The immunological parameters studied were serum protein electrophoresis, serum immunoglobulins (IgG, IgA and IgM), delayed hypersensitivity by Mantoux test, and T-cell % estimation. The mean total serum proteins and serum albumin were significantly lower, whereas mean beta and gamma globulins were elevated. Mean serum IgG and serum IgA showed a significant rise, whereas the T-cell % was significantly reduced when compared to controls. The significance of these findings is discussed. PMID- 2585335 TI - Chronic bronchitis. IV--Antibody titres to bacterial antigens during acute exacerbations. AB - In 49 patients of chronic bronchitis with acute exacerbation, serum antibody titres were estimated against the respective pathogen isolated and cultured from sputum of individual patients. Antibody titres to Klebsiella and Staphylococcus coagulase positive organisms were found in 28 and 25 patients respectively. Paired serum samples from 21 patients showed rising antibody titres in 17 of them, whereas the antibody titres fell in the remaining 4 patients. Notably, only 2 patients demonstrated a four fold rise or fall in the antibody titres. The significance of these findings is discussed. PMID- 2585336 TI - A random plasma glucose method for screening for gestational diabetes. AB - Low renal threshold for glucose during pregnancy renders glycosuria less specific for the diagnosis of gestational diabetes. Screening for gestational diabetes was done by utilising random plasma glucose (RPG). RPG was done at the first antenatal visit. In 12,623 patients who registered for antenatal care at the N.W.M. Hospital, 1371 patients had a RPG more than 100 mg%. An oral glucose tolerance test was advised in these patients. The pick-up rate of gestational diabetes correlated with RPG level. Thirty-six cases of gestational diabetes were picked up. The pick up rate is significantly higher as compared to that which would have been detected utilising conventional screening criteria. PMID- 2585337 TI - Role of pulsed electromagnetic fields in recalcitrant non-unions. AB - Twenty-nine patients of recalcitrant nonunion of long bones were treated by pulsed electromagnetic fields in an attempt to bring about osteogenesis. The pulse used was rectangular, equal mark space wave in the astable, continuous mode operating at a frequency of 40 Hertz. The success rate was 82.5%. The result was not dependent on the age, sex, time of nonunion or the presence of infection. However, the results were uniformly poor when infection and fracture instability were coexistent in the same patient. PMID- 2585339 TI - Post-hysterectomy broad ligament haematoma: a complication of vaginal packing? (A case report). AB - With meticulous surgical technique, bleeding following vaginal hysterectomy and colporrhaphy is an unusual complication. With exteriorization of the stumps, any such haemorrhage is revealed in the form of vaginal bleeding. Two unusual cases of perivesical and broad ligament hematoma are presented and the possible role of vaginal packing in the development of such bleeding is discussed. PMID- 2585338 TI - Fatal outcome of group-G streptococcal meningitis (a case report). AB - An adult woman developed meningitis caused by Group-G streptococci. The organism was successfully isolated both from blood and cerebrospinal fluid of the patient. The woman succumbed to infection despite an appropriate antibiotic therapy. PMID- 2585340 TI - Primary echinococcal cyst of the broad ligament (a case report). PMID- 2585341 TI - Corrosive acid strictures of the stomach (a case report). AB - Two patients presented with history of suicidal acid ingestion. Both the patients developed strictures exclusively in the stomach without involvement of the oesophagus, after a period of 12 weeks. The mechanism of this involvement is presented. The literature on this subject is briefly reviewed. PMID- 2585342 TI - Comparative study of oral and intramuscular atropine sulphate as a premedicant in paediatric age group. AB - The use of atropine sulphate in the paediatric age group as a premedicant orally in a dosage of 0.02 mg/kg body weight 70 minutes prior to surgery was found to be as effective as atropine sulphate given intramuscularly 35 minutes prior to surgery in a dosage of 0.01 mg/kg body weight. This avoids the unpleasant memory of needle prick; The duration of effect as studied in the normal healthy children not subjected to surgery was found to be 2 1/2-3 hours. PMID- 2585343 TI - Segregation and linkage analyses of bipolar and major depressive illnesses in multigenerational pedigrees. AB - Data were collected on six large multigenerational pedigrees, four ascertained through a proband with major depression and two ascertained through a proband with a bipolar form of illness. Diagnoses were made using the SADS-L structured interview and Research Diagnostic Criteria (RDC). Complex segregation analyses were conducted on the bipolar and the major depression pedigree sets using a model allowing for both major locus and polygenic inheritance; in these analyses a variety of diagnostic schemes and assumptions concerning the lifetime population prevalence were examined. Linkage analyses on standard markers were conducted using parameters for transmission of susceptibility to illness derived from the segregation analyses. Results of the segregation analyses were quite sensitive to the diagnostic and prevalence assumptions. In the pedigrees ascertained through probands with a bipolar form of illness, we were unable to discriminate between major gene and polygenic inheritance. The data were compatible with Mendelian major gene transmission of susceptibility to illness when bipolar and schizoaffective manic diagnoses were considered as affected and the lifetime population prevalence was between 0.04 and 0.06. Outside this narrow prevalence range, or when additional diagnoses, such as major depression or hypomania, were included as expressions of liability to disease, major gene transmission of susceptibility to disease could be rejected. Similarly, in the pedigrees ascertained through probands with major depression, it was not generally possible to discriminate between major gene and polygenic transmission of susceptibility to illness. For a diagnostic scheme including only major depression as a manifestation of susceptibility to illness, there was a narrow range of lifetime population prevalence values (female prevalence ranging from 0.20 to 0.25, male prevalence set to 1/2 female prevalence) which yielded results compatible with major gene transmission. Linkage analyses for all markers yielded negative or inconclusive results. In one bipolar pedigree a lod score of 1.65 was found with a marker in chromosome 1 recommending further studies of this chromosome. PMID- 2585344 TI - The reliability and discriminant validity of three potential measures of bulimic behaviours. AB - There is currently a need for a reliable and valid self-report measure of bulimic behaviours that is brief and economical to administer and that can be used to assess response to treatment and to investigate correlates of bulimic symptoms. Three potential screening measures of bulimic behaviours (the Bulimia Test, the Conroy-Healy Eating Questionnaire and the Bulimia subscale of the Eating Disorder Inventory) were evaluated using internal consistency analysis and Receiver (or Relative) Operating Characteristic curve analysis, to determine their internal reliability and ability correctly to identify bulimic patients seen at an eating disorders outpatients clinic. The results showed that the three measures examined were all good discriminators of bulimic and non-bulimic patients. However, the results showed that the Bulimia Test was clearly the most reliable measure, apparently because of its greater length. It is suggested that further investigations be conducted to establish the sensitivity of the Bulimia Test to changes in the severity of bulimic behaviours in patients, since this will increase knowledge of its utility as a measure of response to treatment. PMID- 2585345 TI - General practitioners' characteristics and the assessment of psychiatric illness. AB - We put forward the hypothesis that general practitioners (GPs) with a family medicine orientation are more sensitive to the presence of mental health problems than GPs with a clinical orientation. To test it, GPs were divided into three subgroups on the basis of an attitude questionnaire. The General Health Questionnaire (GHQ) and the Present State Examination (PSE) were used as criteria. No differences in sensitivity to psychiatric illness were observed using either scale. Results of factor analysis with the subscales of the GP attitude questionnaire and the indices 'bias' and 'accuracy' were similar to those reported by GOLDBERG and associates. 'New' patients were defined as patients in whom the GP had not identified a mental health problem (MHP) in the past year. 'Old' patients were defined as 'not new'. GPs tended to under-identify MHPs in 'new' and over-identify them in 'old' patients. Recognition of psychiatric illness was better in 'old' than in 'new' patients. In 'new' patients, recognition depended on psychiatric diagnosis. Among 'old' patients, older people and people (especially women) with low education predominated. In their assessments GPs used information not contained in the GHQ. PMID- 2585346 TI - The predictive power of the salivary cortisol dexamethasone suppression test for three-year outcome in major depressive illness. AB - Seventy patients satisfying DSM-III and Research Diagnostic Criteria for major depression were given a salivary cortisol dexamethasone suppression test, with samples collected at 0700 h, 1500 h and 2300 h after dexamethasone. The patients were classified as nonsuppressors (mean post-dexamethasone salivary cortisol concentration greater than or equal to 2.0 ng/ml, N = 27) and suppressors (mean post-dexamethasone salivary cortisol concentration less than 2.0 ng/ml, N = 43). At 3-yr follow-up there was no difference in illness outcome as assessed by the life table method or by the length of rehospitalisation for several periods after the index episode. In multiple regression and discriminant function analyses, with outcome as the dependent variable (readmitted within 1 yr, readmitted between 1 and 3 yr, not readmitted), the mean post-dexamethasone salivary cortisol concentration was not significantly predictive of outcome. PMID- 2585348 TI - Interpreting the structure of diagnosis in initial evaluations: primary, auxiliary and rule out patterns. AB - The study evaluates DSM III as a natural taxonomy, a system of categories devised for identifying complex objects represented as clinical conditions. Adults seeking initial evaluations constitute the study's population. An individual's clinical condition is examined in terms of a diagnostic format consisting of primary, auxiliary and rule out positions in Axis I and presence and number of diagnoses in Axis II. Each clinical condition thus differs with respect to complexity and diagnostic formats of such conditions are analyzed quantitatively. Differences between the sexes and the races with respect to number of Axis I and Axis II diagnoses are presented. The frequency of use of a diagnostic category is analyzed with respect to position on Axis I, and Axis II, and ratings of the perceived salience and efficacy of treatment plans of the disorders referenced by the category. The number of symptoms in conditions that differ with respect to level of complexity (i.e., number of diagnoses) are compared. An attempt is made to understand how Axis I and Axis II of the DSM III system are used by clinicians and also how they operate as devices to codify clinical information under conditions of relative uncertainty. PMID- 2585347 TI - Age and cortisol suppression by dexamethasone in normal subjects. AB - A study of 60 healthy volunteers ranging from 19-88 yr of age found nonsuppression rare (5%) and confirmed that the dexamethasone suppression test (DST) of the reactivity of the hypophyseal-pituitary-adrenal axis to negative feedback inhibition requires 0800 h plasma dexamethasone (DEX) levels in excess of 220 ng/dl. All of the subjects with inadequate DEX levels (N = 3) were older than 50 yr of age as were the nonsuppressors (N = 3); two of the three nonsuppressors had inadequate DEX concentrations. Thus, DST may be more often invalid in elders than in younger adults because of inadequate plasma dexamethasone (DEX) concentration, indicating that plasma DEX levels should be assayed concomitantly with DST in elders. PMID- 2585349 TI - Linkage analysis of pure depressive disease. AB - In a study of the subgroups of unipolar affective disease, 13 families were ascertained as pure depressive disease (PDD) families. Here we investigate linkage relationships between PDD and 30 genetic markers in these families. Using the robust sib-pair method of linkage analysis, evidence for possible linkage or association was found with five loci: the ABO and MNS blood groups, immunoglobulin kappa (IGK), proline rich parotid salivary protein (PR) and glyoxylase-1 (GLO1). Weak evidence of linkage with ABO was supported using the lod score method of analysis. The maximum lod score between PDD and ABO was 1.42 at a male recombination fraction of 0.09 and a female recombination fraction of 0.03. When these results from the sib-pair analysis were combined with the results from two previous sib-pair studies on PDD, the ABO, MNS and IGK loci were found to be significant (P = 0.05, P = 0.005, P = 0.05, respectively, not allowing for multiple tests). PMID- 2585350 TI - Personality correlates of attributional style. AB - Previous research, much of it based on the learned helplessness model of depression, suggested that a wide variety of personality variables might be related to attributional style. The Attributional Style Questionnaire (ASQ; Peterson et al., 1982) and Comrey Personality Scales (CPS; Comrey, 1970) were administered to 329 subjects, and their scores were subjected to correlational and multiple regression analysis. The CPS scales were also factor analyzed, and the resulting scores were correlated with ASQ scores. Results indicated that a variety of personality variables have statistically significant relationships with attributional style, that these variables show significant positive relationships with internal, stable, and global attributions for positive events and significant negative relationships with these same attributions for negative events, and that an Activity-Extraversion-Stability factor demonstrates the strongest relationships with attributional style. Findings are interpreted within a revised theoretical framework, and emphasis is placed on understanding the personality correlates of attributional style for adequate interpretation of the concept. PMID- 2585351 TI - Correlates of life satisfaction among military wives. AB - Military life includes constant change. This study explored the relationship of life satisfaction among military wives with the individual attitudinal and personality variables of perceived social support, locus of control, and temperament. Sixty wives of noncommissioned military personnel were selected as participants. Life satisfaction was found to be related to high levels of perceived social support from family and from friends, to an internal locus of control, and to low levels of emotionality-stress and emotionality-fear. The results supported the role of individual resources for mediating adjustment and enhancing life satisfaction during the changes inherent in military life. Implications for identifying and helping high-risk women emerged. PMID- 2585352 TI - The principle of additivity and its relation to clinical decision making. AB - Clients (N = 178) with varying degrees of organic indicators were administered a psychological battery including the Memory for Designs Test (MFD; Graham & Kendall, 1960) to assess the extent to which joint presence of organic indicators affected the sensitivity of the MFD in identifying organicity. Joint presence failed to add to the discriminability of the MFD, although individual instruments such as the PIAT (Arithmetic) and WAIS-R (PIQ less than VIQ) clearly discriminated across the MFD. PMID- 2585353 TI - Job involvement and Machiavellianism: obsession-compulsion or detachment? AB - This study addressed a conflicting finding in the Machiavellianism literature- the direction of the relationship between job involvement and Machiavellianism. Although the results did not verify the positive relationship implicit in the view of job involvement as obsession-compulsion, they did confirm the negative relationship implicit in the characterization of Machiavellians as somewhat detached from their surroundings and uninvolved in their jobs. PMID- 2585354 TI - Personality profiles of homosexual men and women. AB - There has been surprisingly little research on possible differences between homosexual and heterosexual personalities, although the few studies that have been conducted suggest some interesting differences. We devised two hypothesis that may account for these differences. First, differences appear to reflect generalized social nonconformity and alienation due to the social stigmatization of the homosexual. Second, these differences seem to express a more specific tendency to deviation from socially normative sex roles. The two hypotheses imply a number of predictions concerning specific personality traits, which were tested by comparing the 16PF (Cattell, Eber, & Tatsuoka, 1970) personality profiles of a group of male (N = 34) and female (N = 31) homosexuals with those obtained from the two large student samples (male, N = 899 and female, N = 912) whose scores are commonly used as norms for the South African version of the 16PF. The findings suggested reasonably good support for the two hypotheses, particularly considering the limitations of the study with respect to the adequacy of the comparison groups used and the relative heterogeneity of the 16PF scale content. PMID- 2585355 TI - Sibling correlates of young adults' status attainment: ethnic group differences. AB - I used longitudinal data to examine relationships between sibling variables and young adults' status attainment at different levels, based on earlier measures of adolescents' educational and occupational aspirations. My analyses involved 21 year-old Australians from Anglo-Australian, Greek, and Southern Italian families. Regression surfaces were plotted from models that included terms to test for possible linear, interaction, and curvilinear associations among the variables. My study showed that the number of children in a family and birth order continue to be significantly associated with young adults' status attainment, even after incorporating the mediating influences of adolescents' aspirations. The investigation also suggested ethnic group differences among sibling variables, adolescents' aspirations, and young adults' status attainment. PMID- 2585356 TI - Alienation among the visually impaired: some important predictors. PMID- 2585357 TI - Frequency and space representation in the primary auditory cortex of the frequency modulating bat Eptesicus fuscus. AB - 1. Frequency and space representation in the auditory cortex of the big brown bat, Eptesicus fuscus, were studied by recording responses of 223 neurons to acoustic stimuli presented in the bat's frontal auditory space. 2. The majority of the auditory cortical neurons were recorded at a depth of less than 500 microns with a response latency between 8 and 20 ms. They generally discharged phasically and had nonmonotonic intensity-rate functions. The minimum threshold, (MT) of these neurons was between 8 and 82 dB sound pressure level (SPL). Half of the cortical neurons showed spontaneous activity. All 55 threshold curves are V shaped and can be described as broad, intermediate, or narrow. 3. Auditory cortical neurons are tonotopically organized along the anteroposterior axis of the auditory cortex. High-frequency-sensitive neurons are located anteriorly and low-frequency-sensitive neurons posteriorly. An overwhelming majority of neurons were sensitive to a frequency range between 30 and 75 kHz. 4. When a sound was delivered from the response center of a neuron on the bat's frontal auditory space, the neuron had its lowest MT. When the stimulus amplitude was increased above the MT, the neuron responded to sound delivered within a defined spatial area. The response center was not always at the geometric center of the spatial response area. The latter also expanded with stimulus amplitude. High-frequency sensitive neurons tended to have smaller spatial response areas than low frequency-sensitive neurons. 5. Response centers of all 223 neurons were located between 0 degrees and 50 degrees in azimuth, 2 degrees up and 25 degrees down in elevation of the contralateral frontal auditory space. Response centers of auditory cortical neurons tended to move toward the midline and slightly downward with increasing best frequency. 6. Auditory space representation appears to be systematically arranged according to the tonotopic axis of the auditory cortex. Thus, the lateral space is represented posteriorly and the middle space anteriorly. Space representation, however, is less systematic in the vertical direction. 7. Auditory cortical neurons are columnarly organized. Thus, the BFs, MTs, threshold curves, azimuthal location of response centers, and auditory spatial response areas of neurons sequentially isolated from an orthogonal electrode penetration are similar. PMID- 2585358 TI - Effects of light on circadian pacemaker development. I. The freerunning period. AB - 1. The effects of raising cockroaches, Leucophaea maderae, in non-24 h light cycles on circadian rhythms in adults were examined. The average period (tau) of freerunning rhythms of locomotor activity of animals exposed to LD 11:11 (T22) during post-embryonic development was significantly shorter (tau = 22.8 +/- 0.47 SD, n = 85) than that of animals raised in LD 12:12 (T24) (tau = 23.7 +/- 0.20 h, n = 142), while animals raised in LD 13:13 (T26) had significantly longer periods (tau = 24.3 +/- 0.21 h, n = 65). Animals raised in constant darkness (DD) had a significantly shorter period (tau = 23.5 +/- 0.21 h, n = 13) than siblings raised in constant light (LL) (tau = 24.0 +/- 0.15 h, n = 10). 2. The differences in tau between animals raised in T22 and T24 were found to be stable in DD for at least 7 months and could not be reversed by exposing animals to LD 12:12 or LD 6:18. 3. Animals raised in either T24 or DD and then exposed as adults to T22 exhibited average freerunning periods that were not different from animals not exposed to T22. 4. Measurement of freerunning periods at different temperatures of animals raised in T22, T24, or T26 showed that the temperature compensation of tau was not affected by the developmental light cycle. These results indicate that the lighting conditions during post-embryonic development can permanently alter the freerunning period of the circadian system in the cockroach, but do not affect its temperature compensation. PMID- 2585359 TI - Effects of light on circadian pacemaker development. II. Responses to light. AB - The effects of raising cockroaches, Leucophaea maderae, in non-24-h light cycles on the response of the circadian system to light was examined. 1. Phase response curves (PRC) were measured for 6-h light pulses for animals raised in LD 11:11 (T22), LD 12:12 (T24), and LD 13:13 (T26). The delay portion of the PRC was found to be significantly reduced in T22 animals (compared to T24 animals) while the advance portion of the PRC was reduced in T26 animals. Compared to T26 animals, phase shifts were more positive at every phase for animals raised in T22. 2. When transferred from constant darkness (DD) to constant light (LL) the freerunning period lengthened significantly less for T22 animals than T24 animals, and in some cases tau in LL was actually shorter than tau in DD in T22 animals. Animals raised in LL were inactive when exposed to LL as adults, and unlike T24 animals, were consistently reset to the beginning of the subjective night (near CT 12) when transferred to DD. 3. Roaches raised in T22 would entrain to LD 6:18, but a few animals exhibited periods of relative coordination indicating that the 24-h light cycle was near the limits of entrainment. These results indicate that the circadian system's responsiveness to light, as well as its freerunning period (Barrett and Page 1989), is dependent on the lighting conditions to which the animals are exposed during development. PMID- 2585360 TI - The code for stimulus direction in a cell assembly in the cockroach. AB - The cockroach Periplaneta americana responds to the approach of a predator by turning away. A gentle wind gust, caused by the predator's approach, excites cercal wind receptors, which encode both the presence and the direction of the stimulus. These cells in turn excite a group of giant interneurons (GI's) whose axons convey the directional information to thoracic motor centers. A given wind direction is coded not by a single GI functioning as a labeled line, but rather by some relationship among the spike trains in an assembly of GI's. This paper analyzes the code in this assembly. It is shown that all three pairs of GI's with the largest axonal diameters respond differentially to wind from left front vs. right front (Figs, 3, 4; Table 2). Each GI encodes these angles by both the time of its first action potential, and the number of action potentials, relative to its contralateral homolog. It is shown that the behavioral discrimination cannot rely solely upon the left-right differences in the time of the first action potential. A model of the assembly code is developed that involves a comparison of the numbers of action potentials in the left vs. the right group of giant interneurons. The model is shown to account for a large number of pre-existing experimental data on direction discrimination. The model requires, however, the involvement of additional cells in the left and right groups, besides the specific GI's whose role had been tested in prior experiments. The model is then tested by further experiments designed to verify the involvement of these added cells. These experiments support the model. PMID- 2585361 TI - Diabetes care and the White Paper--will it work for patients? PMID- 2585362 TI - Prenatal diagnosis and genetic screening. Community and service implications. Summary and recommendations of a report of the Royal College of Physicians. PMID- 2585363 TI - Use of the Nottingham ADL scale in stroke: relationship between functional recovery and length of stay in hospital. PMID- 2585364 TI - Diabetes mellitus on the Zambian Copperbelt. PMID- 2585366 TI - Secrecy-related problems in AIDS management. PMID- 2585365 TI - Endocarditis in Cameroon. PMID- 2585368 TI - Cholestasis associated with extrahepatic bacterial infection in five dogs. AB - Intrahepatic cholestasis associated with severe extrahepatic bacterial infection is well recognized in humans. A similar syndrome is not well characterized in veterinary medicine. Five dogs with severe extrahepatic bacterial infection that developed histologically confirmed intrahepatic cholestasis were selected from the authors' case files. The types of infections included pneumonia, peritonitis secondary to a rectal tear, urinary tract infection, bite wounds, and vegetative endocarditis. Escherichia coli was involved in two of the dogs, mixed infection in one dog, and a gram-positive cocci in the other two dogs. Total bilirubin concentrations ranged from 3.5 to 33.5 mg/dl. Serum liver enzyme activities showed only mild to moderate increases: alkaline phosphatase (ALP, 41-750 IU/l), alanine aminotransferase (ALT, 25-235 IU/l), and aspartate aminotransferase (AST, 99-255 IU/l). Fasting serum bile acids concentration was markedly elevated in the one dog in which it was measured (259 mumol/l). Histologically, the cholestasis was characterized by bile pigment accumulation in hepatocytes, canaliculi, and/or Kupffer's cells. Inflammatory parenchymal changes, when present, were minimal. The findings of hyperbilirubinemia, only a slight increase in the liver enzyme activities, and minimal inflammatory changes in liver tissue specimens in the five dogs with extrahepatic bacterial infections are similar to the findings in intrahepatic cholestasis associated with extrahepatic bacterial infection in humans. PMID- 2585367 TI - Child survival--world survival. An epidemiologist's story. The Lilly lecture 1989. PMID- 2585369 TI - Intracranial lesions in dogs with hemangiosarcoma. AB - A retrospective analysis of 85 dogs with hemangiosarcoma (HSA) that underwent complete necropsy, including gross examination of the brain, was conducted. Grossly identifiable intracranial lesions were present in 17 dogs. Twelve of 85 dogs (14.2%) had brain metastases. Four of 85 dogs (4.7%) had hemorrhagic lesions and/or ischemic necrosis without identifiable tumor. One dog had a primary central nervous system tumor. Signs of intracranial disease were present in six of 85 dogs (7.1%) with HSA; four had brain metastases and two had nonneoplastic lesions. Metastases had a propensity for cerebrum and gray matter. Dogs with brain metastases had more widely disseminated disease than dogs without brain metastases (P less than 0.001). Dogs with pulmonary metastases were at greater risk for developing brain metastases than dogs without pulmonary metastases (odds ratio = 8.31). Although thoracic radiography accurately identified ten of 12 dogs (83%) with pulmonary metastases, too few cases were available to assess the applicability/accuracy of thoracic radiography in predicting the presence or absence of brain metastases in dogs with malignancy and signs of intracranial disease. PMID- 2585370 TI - Postnatal development of brainstem auditory-evoked potentials, electroretinograms, and visual-evoked potentials in the calf. AB - Brainstem auditory-evoked potentials (BAEP), electroretinograms (ERG), and visual evoked potentials (VEP) were recorded for eight calves from birth to 56 days and the values compared with previously determined adult responses. The BAEPs, ERGs, and VEPs recorded within the first 24 hours after birth contained all of the peaks seen in adult recordings. Varying degrees of maturation of the responses were documented as changes in latency and amplitude with age. The BAEPs were adult-like at birth, with latencies falling within the mean, plus or minus one standard deviation, for adult cows. A small but significant decrease in latency with age was seen for the first, second, and fourth peaks of the response. The ERG amplitudes were also within the adult range for the entire period of the study. Latencies to the a- and b-waves declined during the first 14 days and then stabilized at adult values. The VEP latencies decreased with age, with late peaks changing more than early peaks. Latencies of all but the first peak decreased to values less than the adult range. Two VEP amplitudes increased significantly with age. Developmental appears in the calf and other precocious species are compared to those in altricious (nonprecocious) species. PMID- 2585371 TI - A 6-month-old Doberman pinscher with ambiguous genitalia as a first case of X chromosomal monosomy in the dog. PMID- 2585372 TI - [Bone scintigraphy]. PMID- 2585373 TI - [Topographic anatomy of the ethmoid labyrinth in x-ray computed tomography]. AB - These last years the surgical treatment of inflammatory ethmoid disease has been completely modified, with new endoscopic conservative procedures. In a preoperative phase it is mandatory to provide optimal CT imaging of the ethmoid labyrinth, and for this purpose sections perpendicular and parallel to the nasofrontal duct axis are better than axial and coronal slices. The anatomy of the ethmoid is fairly complex; however certain constant anatomic landmarks allow a systematic analysis of the ethmoid labyrinth: the unciform process, the bulla, the middle turbinate, the superior turbinate and their respective basal lamellae. PMID- 2585374 TI - [How to visualize one additional vertebra on profile radiographs of the cervical spine?]. AB - The authors describe a simple technical trick allowing a better study of the cervical spine in subjects with a brevilineal morphology: this consists in placing a small sans block between, the patient's shoulder blades, while exerting the usual traction, thus causing appropriate backward displacement of the shoulders and clearing the lower cervical spine. PMID- 2585375 TI - An investigation of medical discharges from the British Army 1979-1986. AB - Male medical discharges from the British Army were analyzed for the years 1979 1986. There was a sudden increase in 1983 which reached a peak in 1985 caused by a significant rise in rates of discharge as a consequence of lower limbs and muscular overuse conditions, injuries from road traffic accidents, sports and falls. Training injuries showed an increase which, although substantial, failed to reach statistical significance. The highest increase took place in lower limb and muscular overuse conditions in the youngest and most junior members of the infantry, especially when undergoing basic training. This category appears to be at the highest risk of medical discharge. Other teeth arms had the highest incidence of medical discharges from road traffic accidents. The importance of medical discharges may be misunderstood through the underestimation of their incidence and the absence of a capital valuation of the skills and experience of personnel discharged. The discharge of an infantry corporal with 8 years service may mean the loss of a capital of at least 149,599 pounds. Any interventions aimed at reducing the number discharges should be evaluated using the cost benefit approach. Ways of reducing wastage are discussed. PMID- 2585376 TI - British Military Hospital Dharan: the range, mode of presentation and management of malignancies presenting to the department of surgery during 1985-86. AB - British Military Hospital Dharan provides the surgeon with an opportunity, unparalleled anywhere in the United Kingdom to observe and manage a range of malignancies. The historical and contemporary reasons for this are outlined. The paper illustrates the military hospital experience and mode of presentation of a wide range of malignant conditions treated during the tour. Differences from United Kingdom practice are noted and where known, the reasons for this are discussed. Problems in diagnosis, treatment and continuing care, unique to a practice of this kind, are highlighted. The training potential of a hospital of this nature for future military surgeons is discussed. PMID- 2585377 TI - Reproducibility of measurement of pulsatility index by Doppler ultrasound of the anterior cerebral artery of preterm infants. AB - Ten preterm infants were each studied by three observers using a commercial duplex Doppler ultrasound scanner, in order to determine the intra-observer and inter-observer variability in the measurement of pulsatility index (PI) of the anterior cerebral artery. There was considerable difference in estimates of PI, with a mean range of 0.11 between the three observers for each infant. Intra observer variability exceeded inter-observer variability and had a coefficient of variation of 8.4%. The five observers involved in this study had less than six months experience of duplex scanning. The results suggest that the PI can be measured with acceptable reproducibility by personnel with limited experience. PMID- 2585378 TI - Management after coronary by-pass graft surgery: a rehabilitation course induces life style changes which may improve long term graft survival. AB - Too many coronary artery by-pass grafts block within 10 years. Smoking, one risk factor is well managed with over 80% giving up peri-operatively, but hyperlipidaemia is not. Only 27% of such patients on a rehabilitation course knew their cholesterol and 32% had received no dietary advice. As baseline mean cholesterol was high (7.03 mmol/l) this may be a serious omission. After rehabilitation patients have complied for a mean 16.6 months with recommendations on diet (97% remain on a low fat diet) and exercise (now over 3 sessions per week, a level at which long term cardiovascular benefit may be expected). Within 4 months a significant (14%) fall in total cholesterol was achieved. Rehabilitation after by-pass grafting induces life style changes which may improve long term graft survival and should be made more available. PMID- 2585379 TI - Hand injuries sustained during jungle training. AB - During the initial six week period of deployment and jungle training in Belize, a 634 man strong infantry battalion group sustained twenty-three machete hand injuries. Eighteen were treated at battalion level, while five required hospital treatment. The management of these injuries is considered. PMID- 2585380 TI - Scleroderma with rash and clubbing--a case report. PMID- 2585381 TI - Morale in battle--the vulnerable recruit. PMID- 2585382 TI - Rocky mountain spotted fever. PMID- 2585383 TI - Arthropod transmission of AIDS? PMID- 2585384 TI - Unpublished research papers. PMID- 2585385 TI - The place of colposcopy and related systems in gynecological practice and research. PMID- 2585386 TI - Endometrial bacteria in asymptomatic, nonpregnant women. AB - The existence of normal lower reproductive tract flora has been recognized for many years. A study was conducted to identify the possible existence of upper reproductive tract (endometrial) bacteria in asymptomatic women with no history of previous pelvic infection and a normal pelvic examination. Bacteria were recovered from the endometria of 55 women with a double-lumen-catheter-protected brush; six cultures were sterile. Two hundred thirty-one bacterial species were present in 54 endocervical cultures. Type of contraception and phase of the menstrual cycle had no significant effect on the bacterial species recovered. Although contamination by cervical bacteria was possible, there was evidence of separate endometrial flora. PMID- 2585387 TI - Comparison of two endometrial sampling devices. Cotton-tipped swab and double lumen catheter with a brush. AB - The potential for bacterial contamination during transvaginal recovery of endometrial samples in patients with postpartum endomyometritis spawned an investigation into various protective measures and techniques. The confirmation and determination of the extent of contamination was attempted in 120 postpartum women with the diagnosis of postpartum endometritis. Each woman underwent endometrial sampling for bacterial culturing utilizing two devices--an unprotected, cotton-tipped swab and a protective, double-lumen catheter with a brush. Although a statistically greater number of bacterial species were recovered with the swab than with the brush (2.4 vs. 1.6, respectively [P less than .001]), they were not representative of species commonly thought of as causing cervicovaginal contamination. Individual species found with greater frequency with the swab were Streptococcus faecalis (P = .023), Escherichia coli (P = .007), Proteus mirabilis (P = .025), Bacteroides bivius (P less than .001 and Bacteroides melaninogenicus (P = .02). Thus, with proper cervical preparation and an extended-reach, transvaginal, cotton-tipped swab, true fundal specimens were obtained that provided a representative and cost-efficient sample of the infected endometrial cavity. PMID- 2585389 TI - Carcinoma of the vulva. Significance of surgical margin involvement in assessing prognosis. AB - Repeat pathologic analysis was completed in order to independently assign surgical margin status in a group of 61 patients from the Ohio State University gynecologic oncology tumor registry. Patients were entered into the study group after having undergone simple or radical vulvectomy for squamous carcinoma of the vulva. A statement regarding margin status was made following a detailed pathologic review, and parameters--including stage, grade and lymph node involvement--were assigned without regard to outcome. There was no statistically significant difference in the survival or recurrence rate with involved margins. Mean lesion size was significantly larger with involved margins (P less than .05). The survival and recurrence data support a primary surgical attempt at complete excision regardless of the microscopic margin status. PMID- 2585388 TI - Late-second-trimester pregnancy termination with dilation and evacuation in critically ill women. AB - Dilation-and-evacuation procedures were performed on 13 critically ill women between 20 and 24 weeks of gestation. There were no complications. The procedure can play a significant role in the management of selected critically ill women. PMID- 2585390 TI - Coitus during menses. Its effect on endometriosis and pelvic inflammatory disease. AB - Four hundred ninety-eight consecutive new female patients in a private obstetrics gynecology practice were asked about their coital habits during menses (SxMs/F = frequent, SxMs/O = occasional, SxMs/N = never) and history of pelvic inflammatory disease (PID). Endometriosis and tubal infertility factor were diagnosed on laparoscopy or laparotomy. The frequency of endometriosis was higher (P less than .05) in patients with coitus during menses (SxMs/F + O) (17.5%) than in the SxMs/N group (10.9%). The frequency of PID was not different between the SxMs/F + O (10.8%) and SxMs/N (9.7%) groups. Thirty-five percent of the infertility patients had a tubal infertility factor. The frequency of tubal infertility factors was higher in the PID group (78.4%) than in the non-PID group (30.4%) (P less than .001). Endometriosis was associated with an increase in tubal infertility factors (47.9% vs. 33.3% in the nonendometriosis group) but to a lesser degree than PID. The frequency of PID in the group with a tubal infertility factor was higher (22.7% vs. no tubal factor, 3.4%) (P less than .001), and the frequency of endometriosis was higher in the group with a tubal infertility factor (19.3% vs. no tubal factor, 11.5%) (P less than .05). Coitus during menses appeared to increase the chances of endometriosis but not of PID. The rate of tubal infertility factors increased in both PID and endometriosis. PMID- 2585391 TI - In vitro fertilization. Correlation of vaginal cytology and hormonal profile with success rates. AB - Cytologic parameters of the vaginal epithelium in 59 women undergoing in vitro fertilization-embryo transfer (ET) were correlated with plasma levels of 17-beta estradiol and progesterone on the oocyte pickup (OPU) and ET days. On the OPU day a late proliferative/late proliferative-early secretory pattern was observed in 84.6% of the 13 women who conceived (group 1) but in only 52% of the 46 who failed to conceive (group 2) (P less than .04). On the ET day a secretory phase appeared in 100% and 61% of group 1 and 2 patients, respectively (P less than .01). Between the OPU and ET days the mean karyopyknotic index dropped by 60% and 13% in group 1 and 2 patients, respectively (P less than .001). It seems that a high estrogenic effect followed by an advanced progestational environment, on the OPU and ET days, respectively, can provide a favorable milieu for implantation. PMID- 2585392 TI - Myometrial norepinephrine in human pregnancy. Elevated levels in various disorders leading to cesarean section. AB - Myometrial norepinephrine was measured consecutively with high-performance liquid chromatography in women who delivered by cesarean section. The previously recorded marked reduction in tissue norepinephrine at the end of normal pregnancy was confirmed. When cesarean section was performed because of abruptio placentae/hemorrhage, impending asphyxia, dystocia or preeclampsia, the norepinephrine concentrations were six to ten times higher than in normal pregnancy. When an emergency cesarean section was carried out for premature breech presentation, transverse position of the fetus or prolapse of the umbilical cord (following an otherwise-normal pregnancy), the reduced norepinephrine values were not significantly different from those measured in a control group of women who underwent elective cesarean section. It is possible that the abnormally elevated levels of myometrial norepinephrine are part of the primary pathophysiologic condition associated with sympathetic overactivity, resulting in disturbed myometrial circulation and/or motor activity. PMID- 2585393 TI - Premenstrual syndrome improvement after laser ablation of the endometrium for menorrhagia. AB - Laser ablation of the endometrium was performed on 18 patients for menorrhagia. The patients were evaluated for the premenstrual syndrome (PMS) preoperatively and again at three and six months postoperatively. An improvement in both the severity and duration of PMS symptoms was noted postoperatively, and the reduction in menstrual bleeding was correlated with the reduction in PMS symptoms. PMID- 2585394 TI - Adenocarcinoma of the small intestine presenting as an ovarian mass. A case report. AB - A case of primary adenocarcinoma of the small intestine presented as an abdominopelvic mass. The only site of secondary involvement was the left ovary. Postoperatively six courses of 5-fluorouracil, cisplatin and adriamycin were administered. At the 31-month follow-up there was no evidence of recurrent disease. PMID- 2585395 TI - Persistent insulin resistance after normalization of androgen levels in a woman with congenital adrenal hyperplasia. A case report. AB - Treatment of a woman who had 21-hydroxylase deficiency and insulin resistance resulted in normalization of her high androgen levels. The insulin resistance persisted, indicating that the hyperandrogenism was not contributing to it. PMID- 2585396 TI - Irreversible renal failure after intraperitoneal cisplatin administration. A case report. AB - Intraperitoneal cisplatin has been used for localized tumor control to attain high intraperitoneal concentrations while minimizing systemic toxicity. We report on a woman who developed permanent renal failure following a single intraperitoneal dose of cisplatin. Probable factors contributing to this toxicity were mild renal insufficiency from prior intravenous cisplatin and failure to maintain brisk diuresis in the face of volume depletion due to severe vomiting. Although intraperitoneal cisplatin results in high intraperitoneal drug levels, serum levels similar to those seen with intravenous therapy may contribute to severe nephrotoxicity. PMID- 2585397 TI - Endometriosis and perimenarchal tubal torsion. A case report. AB - Tubal torsion and endometriosis were present in conjunction in a perimenarchal girl. PMID- 2585398 TI - How do bacteria cause chronic arthritis? PMID- 2585399 TI - Lack of association of HLA-DR4 with interleukin 1 beta secretion from peripheral blood monocytes in patients with rheumatoid arthritis. AB - The possible association between HLA-DR4 and interleukin 1 beta (IL-1 beta) secretion from peripheral blood monocytes was analyzed using 34 female patients, with definite rheumatoid arthritis (RA). RA monocytes in serum-free medium or medium supplemented with 10% fetal calf serum secreted IL-1 spontaneously. The level of secretion was enhanced by stimulation with pyrogen-free type II collagen as determined by comparison with 30 healthy individuals matched for age and sex. No association between HLA-DR4 and spontaneous or stimulated IL-1 release from RA monocytes was observed. PMID- 2585400 TI - Pulmonary arterial histology and morphometry in systemic sclerosis: a case control autopsy study. AB - Morphometric measurements were performed on pulmonary arteries in 58 patients with systemic sclerosis (20 limited cutaneous and 38 diffuse cutaneous involvement [21 with and 17 without renal crisis]) and age, race, and sex matched autopsy controls. Matched pairs analysis was employed. For arteries of all sizes, the area of the intima and percent luminal occlusion were greater in the limited and diffuse (no renal crisis) groups than in controls, and these differences were statistically significant for large and medium sized vessels. The greatest luminal occlusion was found in limited cutaneous patients, and especially those with clinical evidence of pulmonary arterial hypertension, providing a rationale for the poor response to vasodilator therapy in these patients. PMID- 2585401 TI - The presence of Sjogren's syndrome is a major determinant of the pattern of interstitial lung disease in scleroderma and other connective tissue diseases. AB - A number of patients with scleroderma, Sjogren's syndrome and other connective tissue diseases (CTD) were assessed to ascertain the prevalence of respiratory abnormalities as defined by bronchoalveolar lavage (BAL), standard respiratory function studies and gallium scan of the lung, and the relationship of these abnormalities to the presence or absence of dyspnea. These results suggest that respiratory symptoms are very common in CTD and in scleroderma, particularly if Sjogren's syndrome is also present. Our findings also suggest the presence of 2 patterns of interstitial lung involvement in scleroderma. In scleroderma alone this appears to be characterized by the presence of increased neutrophil proportions in the BAL, decreased DLCO, and no increase in gallium uptake within the lung. Where scleroderma is associated with Sjogren's syndrome, there is an increase in the proportion of lymphocytes in the BAL and respiratory symptoms are very prominent, the latter associated with an increase in gallium uptake within the lung. This suggests that Sjogren's is a major determinant of the pattern of interstitial lung disease seen in CTD. PMID- 2585402 TI - Mechanism of the damaging effect of dermatomyositis mononuclear cells on cultured human skin fibroblasts. AB - We further studied the mechanism of action of peripheral mononuclear cells (MNC) from patients with dermatomyositis (DM) to strikingly suppress fibroblast proliferation in vitro. Attachment of MNC to fibroblasts was closely related to the mechanism. Most of attached MNC were activated T lymphocytes. Conditioned medium alone did not show any effects on fibroblasts. T8 positive cells and monocytes were essential to elicit the effect. Study of 51Cr release demonstrated that DM MNC augmented cytolysis of fibroblasts. It might be concluded that DM MNC possess T lymphocyte mediated cytotoxicity on fibroblasts and this causes the inhibition of fibroblast proliferation. PMID- 2585403 TI - Cell wall fragments from major residents of the human intestinal flora induce chronic arthritis in rats. AB - To investigate the involvement of human intestinal flora in joint inflammation, cell wall fragments of 9 anaerobic gram positive bacteria of the human fecal flora were prepared and tested for arthropathic properties in the rat. A single intraperitoneal injection of cell wall fragments from Eubacterium aerofaciens or Bifidobacterium species induced persistent chronic arthritis, in contrast to those from Eubacterium rectale, Clostridium species and Lactobacillus leichmanii. The results show that cell wall fragments of major residents from the human fecal flora can induce chronic arthritis in the rat and support the hypothesis that normal human intestinal flora plays a role in the induction of arthritis in man. PMID- 2585404 TI - Antibody to streptococcal cell wall peptidoglycan-polysaccharide polymers in sera of patients with juvenile rheumatoid arthritis but absent in isolated immune complexes. AB - Sera of 88 children with juvenile rheumatoid arthritis (JRA) (10 seropositive, polyarticular onset, 29 seronegative, polyarticular onset, 32 pauciarticular onset, and 17 systemic onset) were evaluated for the presence of serum antibodies to streptococcal cell wall peptidoglycan-polysaccharide polymers (PG-PSP). Immune complexes (IC) isolated by the antihuman IgM (HIgM) affinity column method were also evaluated for the presence of antibodies to PG-PSP. Forty-one of 88 patients with JRA (7 of 10 seropositive, polyarticular onset, 11 of 29 seronegative, polyarticular onset, 16 of 32 pauciarticular onset, and 7 of 17 systemic onset) showed elevated levels of antibodies to PG-PSP in their sera. IgM rheumatoid factors (RF) were demonstrated in 70/88 isolated IC fractions of patients with JRA and IgG RF in 7; however, none of the patients demonstrated the presence of antibodies to PG-PSP in their isolated IC fractions from the anti-HIgM affinity column. These data indicate that antibodies are produced to PG-PSP in all JRA onset types, but they are not constituents of isolated IC by the anti-HIgM affinity column method. PMID- 2585405 TI - Chronic family difficulties and stressful life events in recent onset juvenile arthritis. AB - The prevalence of chronic family difficulties, recent stressful life events and socioeconomic status were assessed in 106 families of children with juvenile arthritis, divided in 5 groups according to disease course types. Chronic family difficulties were assessed by semi-structured parent interviews and life events by questionnaires and interviews. Both chronic family difficulties and recent stressful life events appeared in about 2/3 of the families, but a correlation between these were found only for the pauci and polyarticular groups. Chronic family difficulties and recent stressful life events did not differ between groups and were not associated to severity of disease. To what extent stress influences the course of various disease types of juvenile arthritis warrants longitudinal follow-up. For this a life event questionnaire may be valuable. PMID- 2585406 TI - Factor VIII related antigen and childhood rheumatic diseases. AB - Factor VIII related antigen (FVIIIRAg) levels were measured in the plasma of 63 children with rheumatic diseases and 20 controls. High levels were found in patients with systemic juvenile arthritis, systemic lupus erythematosus, dermatomyositis and systemic forms of vasculitis. The amount of circulating FVIIIRAg seemed to be independent of values for erythrocyte sedimentation rate, C reactive protein and fibrinogen, implying that it was not just another acute phase reactant. Rather, a high level of circulating FVIIIRAg most likely reflects the presence of vascular endothelial injury, and this test may be useful in monitoring disease activity in children with rheumatic diseases in which vasculitis is present. PMID- 2585407 TI - Spontaneous osteoarthritis in rhesus macaques. I. Chemical and biochemical studies. AB - We analyzed the articular cartilage of 41 rhesus macaques for elemental concentrations including [Ca] calcium, [P] phosphorus, [Mg] magnesium, [S] sulfur, [K] potassium and glycosaminoglycan (GAG) and collagen content. Our findings revealed an increase in all elements with aging. Within the osteoarthritic (OA) groups, young OA had higher levels of all elements than old OA, and significantly greater levels compared to young normals. In addition, GAG content was dramatically increased in young OA. Old OA did not differ from old normals for any elements although GAG levels decreased. Collagen was shown to be stable with increasing age in both normal and OA cartilage, but decreased in OA cartilage. This macaque model of spontaneous OA is valuable because it demonstrates early OA changes typical of experimental models and late changes similar to human OA. PMID- 2585408 TI - Comparing the short and long versions of the Arthritis Impact Measurement Scales. AB - Evidence is presented for the utilization of a shortened version of the Arthritis Impact Measurement Scales. The results confirmed that the shortened versions retained adequate internal consistencies, test-retest reliabilities, and both concurrent and predictive validities over a 2 year period which were similar to the original longer versions. PMID- 2585409 TI - An assessment of the Arthritis Impact Measurement Scales in 3 ethnic groups. AB - The Arthritis Impact Measure Scales (AIMS) have established validity and reliability in general adult populations with medically diagnosed rheumatoid arthritis. Our analysis extends this work to a community based sample of elderly individuals with self reported joint systems in 3 ethnic groups: Hispanics (N = 100), whites of Eastern European origin (N = 112) and blacks (N = 105). With the exception of the Social Activity and ADL scales, acceptable reliability and validity of the AIMs scales are found for all 3 groups. The assumption of factor invariance across ethnic groups is also supported. PMID- 2585410 TI - Diffuse idiopathic skeletal hyperostosis and situs viscerum inversus. AB - We describe a 74-year-old woman with diffuse idiopathic skeletal hyperostosis (DISH) and situs viscerum inversus. The radiographic alterations typical of DISH were present only on the left side of her thoracic spine. The role of the thoracic aorta in preventing DISH adjacent to its side and some pathogenetic aspects of this skeletal disorder are discussed. PMID- 2585411 TI - Acute, reversible hepatic failure associated with methotrexate treatment of rheumatoid arthritis. AB - We describe 2 patients who developed reversible decompensated liver disease while taking pulse dosed methotrexate (MTX) for rheumatoid arthritis. One of the patients was available for biopsy and had chronic active hepatitis--a lesion not previously described with MTX. This appears to be a unique and unusual manifestation of MTX hepatotoxicity. PMID- 2585412 TI - Splenic hypofunction in systemic lupus erythematosus: response to pneumococcal vaccine. AB - A woman who presented with splenic hypofunction as a complication of systemic lupus erythematosus is described. Pneumococcal vaccine was given. Her antibody response was measured and the responses of other cases are discussed. PMID- 2585413 TI - Massive pulmonary hemorrhage in mixed connective tissue diseases. AB - We report a patient with mixed connective tissue disease (MCTD) who suddenly developed pulmonary distress with bilateral pulmonary infiltrates. She died in 24 h and was found at necropsy to have had a massive alveolar hemorrhage, as well as renal necrotizing vasculitis and immune complex deposits in the glomeruli. One previous case of MCTD with pulmonary hemorrhage was found in the literature. Recognition of this complication of MCTD may help in its early diagnosis. PMID- 2585414 TI - Linear scleroderma, hemiatrophy and systemic lupus erythematosus. AB - A young woman, with linear scleroderma accompanied by body hemiatrophy since childhood, developed systemic lupus erythematosus. The rare coexistence of the 2 diseases is discussed. PMID- 2585415 TI - Camptodactyly, polyepiphyseal dysplasia and mixed crystal deposition disease. AB - A sporadic case of camptodactyly and arthropathy is described in a 54-year-old man. Polyepiphyseal dysplasia complicated by the so called "chondrodysplastic rheumatism" was a main feature of the arthropathy which included early onset osteoarthritis, calcium pyrophosphate dihydrate and calcium phosphate deposition diseases. We suggest that epiphyseal dysplasia, chondrocalcinosis and mixed crystal deposition disease could be an additional cause of a camptodactyly arthropathy syndrome. PMID- 2585416 TI - Paradoxical disturbances of sex hormone levels in postmenopausal women with systemic lupus erythematosus. PMID- 2585417 TI - Destructive spondyloarthropathy in longterm CAPD and hemodialysis. PMID- 2585418 TI - Concomitant ankylosing spondylitis and DISH. PMID- 2585419 TI - Taking chance out of living--and dying: the Merseyside Accident Information Model (MAIM) PMID- 2585420 TI - Proctocolectomy and ileostomy for ulcerative colitis: the longer term story. AB - Elective surgery for ulcerative colitis usually involves the removal of the entire large bowel with either a conventional ileostomy or the formation of an ileoanal pouch anastomosis. Seventy patients undergoing a one stage elective total proctocolectomy and ileostomy between 1976 (the first year an ileoanal pouch was carried out in this hospital) and 1986 have been studied. We have confirmed that proctocolectomy and ileostomy for ulcerative colitis is not the trouble free operation many presume it to be when considering the alternative of an ileoanal pouch. PMID- 2585421 TI - Evaluation of a 'DIY' test for the detection of colorectal cancer. AB - A new type of faecal occult blood test, EZ-Detect, has been evaluated in 404 patients presenting with symptoms suggestive of colorectal disease. The test avoids handling of stools and gives a result which patients can read themselves- factors which may increase patient compliance. In comparison with the Haemoccult test, EZ-Detect has the same sensitivity for blood in laboratory conditions. In clinical use 98% of patients expressed a preference for EZ-Detect but it detected significantly fewer patients with cancer than did Haemoccult (P = less than 0.05). In its present form, this type of test would be unsuitable for population screening for colorectal cancer even if improved compliance is achieved. PMID- 2585422 TI - Thrombolysis for acute myocardial infarction in a district general hospital. AB - We report our experience in establishing thrombolysis as a routine part of the management of patients with acute myocardial infarction in our hospital; with particular reference to the effectiveness of the policy, safety and delays in administration. PMID- 2585423 TI - Septicaemia in patients with temporary and permanent endocardial pacemakers. AB - Twenty-four patients with staphylococcal septicaemia due to permanent (14) and temporary (10) endocardial pacemakers were reviewed. With permanent pacemakers local inflammation was usually present and the onset of septicaemia rapid. If patients were treated with high dose intravenous flucloxacillin combined with removal, recovery was usual. In patients with retained endocardial tips (6) we eradicated infection with medical treatment alone in four cases. We would advocate antistaphylococcal prophylaxis for patients undergoing revision in the presence of local inflammation and high dose intravenous flucloxacillin plus a second anti-staphylococcal antibiotic (e.g. gentamicin) in patients with septicaemia and a pacemaker in situ. PMID- 2585424 TI - Coronary atherosclerosis and myocardial infarction in autopsied patients in Gondar, Ethiopia. AB - Autopsy study of 124 Ethiopian patients for atherosclerotic lesions and myocardial infarction revealed aortic lesions in 58 (47%), coronary lesions in 26 (21%) and myocardial infarction in 8 (6.5%) cases. Fatty streaks in the coronary arteries were detected after the age of 19 years. Thereafter the frequency increased gradually with age reaching a peak of 33.3% by the age group of 50-59 years. Fibrous plaque appeared at the age of 40 years and progressed with age reaching a maximum of 44.4% by the age of 60-69 years. Myocardial infarction was the cause of sudden death in two cases. Six of the patients with myocardial infarction had moderate to severe lesions. Calcification with narrowing of the left anterior descending coronary artery was found in a 60-year-old female. The significance of the increasing incidence of CHD in black Africans and particularly in Ethiopians is discussed. PMID- 2585425 TI - Exclusion from resuscitation. AB - Resuscitation was attempted for 156 (19.9%) of the 783 cases in St Thomas's Hospital, aged 16 or over, who suffered first cardiac or respiratory arrest of the current admission during the year to 13 April 1987. Seventeen (11%) of the 156 were discharged alive from hospital after resuscitation. All seventeen had been active outside the home before admission, and all except one remained so after discharge. The factors which were associated with exclusion from resuscitation attempts are analysed. Most accorded with known prognostic factors, but resuscitation was attempted for some persons who seemed to have little chance of benefiting from resuscitation attempts. Routine collection, analysis, and dissemination of information on pre-arrest characteristics in relation to their outcome, on which clinicians can base their decision to with-hold resuscitation in the event of an arrest, is recommended. PMID- 2585426 TI - Ten years experience of a genetic eye clinic: 1978-1987. AB - Over a ten year period of running a joint ophthalmological/genetic clinic, 387 index patients were advised, and a further 260 individuals (relatives of the above) were examined and counselled. Determination of the precise diagnoses and modes of inheritance in the index patients necessitated retinal function tests in 267 (69%) and examination of 84 of their parents and 23 sisters and daughters. Finally, 41% of index patients and 39% of their relatives were given high risks for transmitting an autosomal dominant or X-linked disorder to their children. It is noteworthy that 16% of these high-risk index patients and 66% of these high risk relatives had no visual symptoms; ophthalmological expertise was required to assess the significance of their minor signs. It was concluded that an active Register is required for contacting relatives outside the nuclear family, and for future recall of children currently too young for carrier tests or genetic counselling. PMID- 2585428 TI - Development and involution of the notochord in the human spine. AB - The availability of a collection of fetal and embryonic spines made possible a review of the involution of the notochord. Results of this histological, histochemical and immunohistochemical study are in accord with the dominant view in the literature that the notochord does not contribute materially to the adult nucleus pulposus. It is also consonant with the expectation that, normally, all chordal cells have disappeared during early childhood, but is not sufficiently detailed to assess the possibility of occasional survivors. PMID- 2585427 TI - Prevalence, detection and referral of psychiatric morbidity in general medical patients. AB - Twenty seven per cent of medical emergency admissions were found to have diagnosable psychiatric disorders, mostly mild. Although ward staff assessed 31.1% of admissions as having emotional or psychological problems, only a minority had diagnosable psychiatric disorders. Few patients were referred for specialist psychiatric help. This partly reflected the milder nature of problems identified by ward staff, and partly indifference to psychiatry. PMID- 2585429 TI - Faecoptysis as the presenting symptom of colonic carcinoma. PMID- 2585430 TI - Cat scratch disease presenting as a lump in the parotid region. PMID- 2585431 TI - Benign caecal ulceration presenting with life threatening haemorrhage. PMID- 2585432 TI - Faeco-pneumothorax as the presenting feature of a traumatic diaphragmatic hernia. PMID- 2585434 TI - Interrelation between alcohol and accidents. PMID- 2585433 TI - Chronic asthma and hypnotherapy. PMID- 2585435 TI - The future of general anaesthesia in dental surgery. PMID- 2585436 TI - Seat belt injuries. PMID- 2585437 TI - Prader-Willi syndrome. PMID- 2585438 TI - A novel solution-stable, water-soluble prodrug type for drugs containing a hydroxyl or an NH-acidic group. PMID- 2585440 TI - Enkephalinase inhibitors. 1. 2,4-Dibenzylglutaric acid derivatives. AB - The synthesis of two new series of dicarboxylic acid dipeptides and two sulfhydryl-containing inhibitors are described. The in vitro enkephalinase inhibition data and some in vivo analgesic data are presented for these compounds. For the dibenzylglutaric acid series structure-activity relationships and in vivo analgesic activity are discussed. The reverse amides, i.e., 4-amino 2,4-dibenzylbutyric acid derivatives, are also discussed. Two sulfhydryl containing inhibitors showed good in vivo potency in the mouse jump-latency hot plate test after peripheral administration at moderate low doses. PMID- 2585439 TI - Thienothiopyran-2-sulfonamides: novel topically active carbonic anhydrase inhibitors for the treatment of glaucoma. PMID- 2585441 TI - Derivatives of tamoxifen. Dependence of antiestrogenicity on the 4-substituent. AB - A range of tamoxifen derivatives substituted in the 4-position of the 1-phenyl ring are described. The key steps in the synthesis of 4-iodo-, 4-bromo-, and 4 (methylthio)tamoxifen were reactions of 1,2-diarylbutanones with the (4 halogenophenyl)lithium or [4-(methylthio)phenyl]magnesium bromide. Oxidized precursors of 4-(methylthio)tamoxifen were used to prepare the methylsulfinyl and methylsulfonyl derivatives. Further derivatives (formyl, hydroxymethyl, oxirane, mercapto) were prepared from 4-bromotamoxifen via the 4-lithio derivative. Several of the derivatives (Br, I, SMe, SOMe, SO2Me, oxirane, CHO, CH2OH) displayed a higher affinity for estrogen receptors (ER) of calf uterine cytosol than did tamoxifen, but there was no relationship between affinity to ER and the ability to inhibit the growth of the MCF-7 breast cancer cell line in vitro. PMID- 2585442 TI - 4-Phenyl- and 4-heteroaryl-4-anilidopiperidines. A novel class of analgesic and anesthetic agents. AB - The incorporation of the 4-phenylpiperidine pharmacophore found in morphine into 4-anilidopiperidines related to fentanyl (1) led to a novel class of potent opioid analgesic and anesthetic agents with a favorable pharmacological profile. The synthesis, analgesic activity, and anesthetic properties of a series of 4 phenyl-4-anilidopiperidines (13-29) are discussed. Isosteric replacement of the phenyl by various heteroaryl substituents extended the series to include 4 heteroaryl-4-anilidopiperidines (30-53). Within this group, 1-[2-(1H-pyrazol-1 yl)ethyl]-4-(4-methylthiazol-2-yl)-4-(N- phenylpropionamido)piperidine (48), exhibited high analgesic potency, short duration of action, rapid recovery of motor coordination following anesthetic doses, and greater cardiovascular and respiratory safety during anesthesia as compared with opioids fentanyl (1) and alfentanil (2) currently in clinical use. Such analgesics could be of great utility to clinicians in the expanding outpatient surgical arena and for patient controlled analgesia and computer assisted continuous infusion pain control techniques. PMID- 2585443 TI - Topically active carbonic anhydrase inhibitors. 2. Benzo[b]thiophenesulfonamide derivatives with ocular hypotensive activity. AB - Derivatives of benzo[b]thiophene-2-sulfonamide were prepared to investigate their potential utility as topically active inhibitors of ocular carbonic anhydrase. Such an agent would be useful in the treatment of glaucoma. Among the compounds described are 6-hydroxybenzo[b]thiophene-2-sulfonamide (16) and its acetate ester (23), which are among the most potent ocular hypotensive agents in this class, as assessed in the alpha-chymotrypsinized rabbit. These compounds were selected for clinical evaluation. PMID- 2585445 TI - Comparative fine structure of the eggs of Aedes albopictus, Ae. aegypti, and Ae. bahamensis (Diptera: Culicidae). AB - Complete descriptions, including details of the micropylar apparatus and outer chorion at the anterior and posterior poles and on the dorsal surface, are given for the eggs of Aedes (Stegomyia) albopictus Skuse and Ae. (S.) aegypti (L.). The egg of Ae. (Howardina) bahamensis Berlin, the first of this subgenus to be examined with the electron microscope, is described for the first time. Certain characters may be useful for differentiating eggs of these three species under a stereomicroscope. The substantially greater egg length in Ae. bahamensis alone separates it from the other two species, at least in the laboratory populations studied. The micropylar collar in Ae. aegypti clearly differentiates it from the other two. Further examination of mixed groups of eggs is needed to determine whether fine structural differences in the outer chorion can be correlated with consistent differences in the stereomicroscopic image. PMID- 2585444 TI - Flight behavior of Musca domestica and Stomoxys calcitrans (Diptera: Muscidae) in a Kansas dairy barn. AB - Aerial density, flight thresholds, and periodicity were estimated for the house fly, Musca domestica L., and the stable fly, Stomoxys calcitrans (L.), from data collected by suction traps located in a dairy barn in Kansas between 1 July and 31 October 1970. M. domestica catches increased from July to August, declining to near zero by the end of October. S. calcitrans catches peaked in July and September with a major decline in August. Both species exhibited a diel periodicity in flight with maximal activity during the early afternoon. Secondary peaks were detected in the late afternoon or early evening. M. domestica activity peaked about two hours after S. calcitrans. Male and female S. calcitrans flight activity patterns were slightly different, but peaked at the same time. Both species flew at temperatures between 20 and 38 degrees C. At temperatures over 33 degrees C, stable fly activity decreased rapidly. No upper threshold for flight by M. domestica was detected. The median temperature-flight thresholds of male and female S. calcitrans were significantly different, with females flying at lower temperatures than males. The threshold for M. domestica flight was lower than for S. calcitrans. The shape of the temperature-flight relationship indicated that the flight threshold was determined by heat accumulation. PMID- 2585446 TI - Rearing Dictya floridensis (Diptera: Sciomyzidae) in a continuously producing colony and evaluation of larval food sources. AB - Methods for large-scale continuous propagation of Dictya floridensis Steyskal were developed. A colony originating from 22 specimens of several Dictya species collected in Alachua County, Fla., became a single species colony after several generations because of failure of all but D. floridensis to survive colonization. The colony was maintained as separate generations until the F5, after which new D. floridensis adults were pooled into mass colony cages. During the F7 generation, colony production was in excess of 1,000 neonate larvae per day, the number of adults was continually increasing, and the females had extended longevity and fecundity. At that time, the colony was considered to be continuously producing, and size of the colony was limited only by the availability of food and rearing facilities. Larvae were reared on living, freshly crushed, frozen snails, Physella hendersoni hendersoni (Clench) and Pseudosuccinea columella Say. Larval development and their survival rate to pupariation was the same whether reared on freshly crushed snails or on live food. Larvae reared on frozen snail tissue compared with live snails had the same sex ratio but were lighter in weight and had extended development time to pupariation and lowered survival rates. Larvae fed and developed successfully upon living embryonated snail egg masses but were unable to use egg masses that had been frozen. PMID- 2585447 TI - Environmental factors influencing oviposition by Culex (Culex) (Diptera: Culicidae) in two types of traps. AB - Seasonal and habitat influences on the egg-laying activity of four species of Culex were compared in south Florida using jar- and vat-type oviposition traps. Egg rafts of Culex nigripalpus Theobald, Cx. quinquefasciatus Say, and Cx. salinarius Coquillett were collected in every month of the year, but rafts of Cx. restuans Theobald were absent during spring and summer. Cx. nigripalpus was the dominant species in the summer and fall, and Cx. quinquefasciatus and Cx. salinarius peaked during the winter and spring. Cx. restuans oviposited most rafts in the fall (98.4%). Most Cx. nigripalpus egg rafts were laid in vats (88.5%), and most Cx. quinquefasciatus egg rafts were deposited in jars (58.7%). Fewer Cx. quinquefasciatus rafts were found in a wooded area (32.4%) with a dense undergrowth than in a more open area (67.6%), but Cx. nigripalpus showed no ovipositional preference between these two habitats. The number of rafts oviposited by all species was reduced during periods of rainfall. PMID- 2585448 TI - Size of blood meals of Aedes albopictus and Culex tritaeniorhynchus (Diptera: Culicidae) feeding on an unrestrained dog infected with Dirofilaria immitis (Spirurida: Filariidae). AB - Blood meal volume was determined for two species of mosquitoes, Aedes albopictus (Skuse) and Culex tritaeniorhynchus Giles, recently demonstrated to be natural vectors of canine heartworm in Japan. When fed on unrestrained dogs, volumes were from 1 nl to 6 microliters in both species, but percentages of engorged mosquitoes were 45.2-64.3% for Ae. albopictus and 11.9-22.2% for Cx. tritaeniorhynchus. Ae. albopictus preferred to feed on human bait versus canine bait when both were exposed concurrently. PMID- 2585450 TI - Two new species of schoengastiine chiggers (Acari: Trombiculidae) from Brazil and rediagnosis of Arisocerus Brennan, 1970. AB - Colicus spinosus Goff & Gettinger, n. sp., is described from Marmosa agilis. Quadraseta brasiliensis Goff & Gettinger, n. sp., is described from Marmosa agilis, Monodelphis americana, and Oryzomys capito. All specimens were collected in central Brazil. The diagnosis of the genus Arisocerus Brennan, 1970, is corrected to describe the setation of the palpal tarsus as 7BS rather than 6BS as listed in the original description. PMID- 2585449 TI - Species recognition elicited by differences in composition of the genital sex pheromone in Dermacentor variabilis and D. andersoni (Acari: Ixodidae). AB - The chemical basis for the ability of fed males of Dermacentor variabilis (Say) and D. andersoni (Stiles) to differentiate conspecific and heterospecific females was investigated using a neutered female bioassay. Male D. variabilis responded strongly in a dose-response manner to increasing concentrations of stearic and palmitic acids and an extract of the anterior reproductive tract (ART) of fed D. variabilis females. Mating responses were greatest at 1 microgram of fatty acid and 1 female equivalent (FE) of ART extract. D. variabilis males also responded strongly to D. variabilis females treated with a conspecific ART extract and a mixture of fatty acids simulating the extract; responses were moderate to D. andersoni females treated with the same extract or fatty acid mixture. They also responded moderately to conspecific females treated with D. andersoni extract. Male D. andersoni displayed moderate increases in mating behavior over a range of concentrations of stearic and palmitic acids and conspecific ART extract. D. andersoni males mated only with D. andersoni females treated with a conspecific extract or a mixture of fatty acids simulating the extract. Mating by D. andersoni did not occur in response to D. variabilis females treated with D. andersoni or D. variabilis ART extracts. Stearic acid alone or in combination with 20-hydroxyecdysone, oleic, or myristic acid did not account for the specificity of response of either species. D. andersoni males were much less responsive to fatty acids, alone or in mixtures, than D. variabilis males. These findings indicate that fatty acids are important in mate recognition by D. variabilis, but explain only part of that by D. andersoni. The possibility is raised that another compound is required for mate recognition by D. andersoni. PMID- 2585451 TI - A quantitative survey of Culicoides variipennis (Diptera: Ceratopogonidae) in dairy wastewater ponds in southern California. AB - Culicoides variipennis (Coquillett) larvae were sampled five times over a 10-wk period in late summer in each of 26 dairy wastewater ponds in western Riverside County, Calif. Slope, degree of cattle access, prevalence of visible manure solids, salinity, chemical oxygen demand, plankton volume, and whether the ponds were pumped for irrigation were determined concurrently. Larvae of C. variipennis were associated positively with plankton volume, degree of animal access, and salinity, and negatively with slope and the pumping of the ponds for irrigation. High densities of larvae were found in shoreline mud in shallow, "evaporation bed" type ponds that were not pumped (means = 106 larvae per 30 ml). In contrast, pumped ponds were deeper, had steeper slopes, and supported lower densities of C. variipennis (means = 52 larvae per 30 ml). The pumped ponds tended to hold water continuously (more stable in time), and to have lower phytoplankton volumes and lower values of chemical oxygen demand. Rapid water level fluctuations in the pumped ponds also may have reduced C. variipennis density. PMID- 2585452 TI - Response of Culicoides variipennis (Diptera: Ceratopogonidae) to water level fluctuations in experimental dairy wastewater ponds. AB - Water levels were fluctuated in experimental dairy wastewater ponds in southern California to study the response of Culicoides variipennis (Coquillet). Immatures consistently were found in surface mud at the water's edge in ponds where the water level was stable. In ponds where the water level was fluctuated, immatures did not relocate to the new, lower waterline when the water quickly receded 3 m in horizontal distance. Younger larvae apparently were stranded above the waterline and were killed by heat or desication, or both; pupae and late fourth instars emerged as adults at the old waterline. A larvae were recovered from fairly dry mud up to 19 d after the water level receded. Substantial oviposition occurred at the lower waterline following the water level decrease, and adults began to emerge 14-18 d later. Immatures relocated to the higher waterline 3 h to 2 d after a rise in water level. Densities of this species were slightly, but not significantly, reduced in the fluctuated ponds under this water management regime. Water level fluctuations at 1-wk intervals might be expected to reduce substantially C. variipennis production from these habitats. PMID- 2585453 TI - Keys to the adult ticks of Haemaphysalis Koch, 1844, in Thailand with notes on changes in taxonomy (Acari: Ixodoidea: Ixodidae). AB - Specimens of the genus Haemaphysalis collected in Thailand were examined, and a key to the adult of 24 species belonging to six subgenera is presented. We propose that H. wellingtoni Nuttall & Warburton, 1908, be placed in the subgenus Kaiseriana; H. obesa Larrousse, 1925, be moved from Segalia to Kaiseriana; and that H. cornigera Neumann, 1897, be removed from the species list of Thailand. PMID- 2585454 TI - Replication and dissemination of La Crosse virus in the competent vector Aedes triseriatus and the incompetent vector Aedes hendersoni and evidence for transovarial transmission by Aedes hendersoni (Diptera: Culicidae). AB - The time course and pattern of the replication and dissemination of La Crosse virus was studied in orally infected Aedes triseriatus (Say) and Ae. hendersoni Cockerell. Development of La Crosse virus was approximately the same in both species when plaque assay titers of intact mosquitos or dissected tissues were compared. The mosquitoes were equally susceptible to infection; all Ae. hendersoni and 99% of the Ae. triseriatus tested showed detectable midgut infections. Virus was first detected in hemolymph, salivary glands, and ovaries 10-13 d after infection in both species. The pattern of infection suggests virus dissemination beyond the midgut to be via the hemolymph. By 21 d after infection, 100% (10 of 10) of Ae. triseriatus and 70% (7 of 10) of Ae. hendersoni had infected salivary glands, and the geometric mean titer of Ae. hendersoni salivary glands was 10 times higher than the geometric mean titer of those of Ae. triseriatus, However, when tested for transmission 22 d after infection by refeeding on suckling mice, only 9% (2 of 22) of the Ae. hendersoni with disseminated infections transmitted virus versus 71% (12 of 17) of the Ae. triseriatus. A salivary gland escape barrier was shown to be primarily responsible for the failure of Ae. hendersoni to orally transmit La Crosse virus. However, eight parenterally infected Ae. hendersoni females transovarially transmitted the virus to 25% (5 of 20) of their progeny. PMID- 2585455 TI - Seasonal activity and survival of adult Ixodes dammini (Acari: Ixodidae) in southern New York State. AB - Mark-recapture studies demonstrated that adult Ixodes dammini Spielman, Clifford, Piesman, and Corwin in southern New York successfully overwinter and resume active host-seeking in the spring. Thus, the resulting bimodal peak in autumn and spring appears to reflect temperature-induced activity of the same cohort and not different generations. Adult tick abundance in the field was monitored by counting the number of ticks collected by a domestic dog on routine walks and correcting for the effects of temperature on tick activity. It is suggested that adult abundance, measured independently of ambient temperature, may be an accurate indicator of survival. The field tick abundance curve was negatively exponential (y = e(4.26-0.12x] and significantly different from the survival curve for ticks maintained in the laboratory, which displayed a constant mortality rate (y = -3.7x + 105.5). Body size influenced male survival during the winter, whereas female survival was independent of body size. Greater male mortality in fall and winter resulted in a lower sex ratio in spring. PMID- 2585456 TI - Interspecific competition among Aedes aegypti, Ae. albopictus, and Ae. triseriatus (Diptera: Culicidae): larval development in mixed cultures. AB - Interactions among the larvae of Aedes aegypti (L.), Ae. albopictus (Skuse), and Ae. triseriatus (Say) were studied in trispecific and bispecific mixed populations under laboratory and field conditions. Competitive stress (as evidenced by the average time to first, 50, and 75% pupation and the total pupation periods for mixed populations of each species in comparison with their single species controls) was more pronounced in mixed cultures reared in glass jars in the laboratory than in tires under field conditions. In the laboratory, the larval development of Ae. aegypti reared together with Ae. albopictus or Ae. triseriatus, or both, larvae was accelerated significantly. Conversely, the time to pupation for Ae. albopictus and Ae. triseriatus was delayed when reared with Ae. aegypti. However, the average wing length of female Ae. albopictus and Ae. triseriatus was greater in the mixed cultures than in single species cultures. These data indicated that the effect of intraspecific competition was greater than interspecific competition. Adequate food and higher temperature appeared to promote rapid development and higher survival of the immature stages of the three Aedes species in tires placed in the field. In general, Ae. triseriatus larvae required a longer period for larval development and had greater larval mortality than either Ae. aegypti or Ae. albopictus. In mixed populations of Ae, albopictus and Ae. aegypti in the jars and food-rich tires, the periods needed to attain first, 50, and 75% cumulative pupation were not significantly different than in single species controls. We conclude that no clear-cut displacement occurred in mixed experimental populations of Ae. aegypti and Ae. albopictus. PMID- 2585457 TI - Natural control of larval Anopheles albimanus (Diptera: Culicidae) by the predator Mesocyclops (Copepoda: Cyclopoida). AB - Forty-two ground water sites on the Pacific and Atlantic coasts of Colombia were sampled quantitatively with a plankton net to assess the abundance of mosquito larvae and associated fauna. Many of the sites contained substantial numbers of Anopheles albimanus Wiedemann larvae, but the larvae were virtually absent wherever there were large populations of the copepods Mesocyclops venezolanus, M. longisetus, or M. aspericornis. Mesocyclops were observed to prey readily upon first-instar An. albimanus larvae in the laboratory, but smaller genera of cyclopoid copepods did not kill An. albimanus larvae. We conclude that Mesocyclops may prove useful for biological control of Anopheles. PMID- 2585458 TI - Focus of human parasitism by the brown dog tick, Rhipicephalus sanguineus (Acari: Ixodidae). AB - Throughout most of its range, the brown dog tick, Rhipicephalus sanguineus (Latreille), prefers dogs as a host, but human bites occasionally occur in the Mediterranean region and Central America; historically, this species has rarely bitten humans in the United States. A focus of 15 human bite cases by this tick is reported from four Air Force bases located within 200 miles of each other in north central Texas and southwestern Oklahoma. The sudden appearance of numerous documented bite cases indicates that either the species is becoming more anthropophilic in this area or than an introduction of a more human adapted population of R. sanguineus has occurred. The species is a known reservoir and vector of Ehrlichia canis, the causative agent of canine ehrlichiosis in dogs. The presence of an anthropophilic strain of R. sanguineus in the United States may lead to increased exposure to E. canis and thus an increase in the incidence of human ehrlichiosis. PMID- 2585460 TI - Familial mental retardation associated with balanced chromosome rearrangement rcp t(8;11)(q24.3;p15.1). AB - We report three sisters and their father with a reciprocal balanced translocation, rcp t(8;11)(q24.3;p15.1) and the same abnormal phenotypes, including mental retardation, growth disturbance, and amblyopia. It is considered that the abnormal phenotypes in our four cases might result from a tiny deletion or gene mutation at the breakpoints in 8q or 11p or both. Our cases showed no resemblance, apart from mental retardation, to Langer-Giedion syndrome, which is caused by the deletion of 8q23.3 and 8q24. Furthermore, our patients did not have the cardinal features of Beckwith-Wiedermann syndrome or WAGR which are caused by deletion of 11p. It is suggested that the amblyopia in our four cases might have resulted from the breakpoints at 11p15.1. PMID- 2585459 TI - Transient nephrotic syndrome after anaesthesia resulting from a familial cryofibrinogen precipitating at 35 degrees C. AB - Transient nephrotic syndrome, haematuria, and cryofibrinogenuria in a child after anaesthesia were found in association with a plasma cryofibrinogen that precipitated at 35 degrees C. Investigation of the family showed this to be a familial trait probably with dominant inheritance. PMID- 2585461 TI - A new interstitial deletion of 4q (q21.1::q22.1). AB - A unique case of de novo interstitial deletion of chromosome 4 is described involving loss of band q21. The male newborn had multiple abnormalities including frontal bossing, prominent occiput, low set ears, micrognathia, short sternum, short, broad hands and feet, agenesis of the corpus callosum, and cardiac defects. The phenotypic abnormalities are compared with other reported cases of deletion 4q involving adjacent regions. PMID- 2585462 TI - Cat eye syndrome associated with aganglionosis of the small and large intestine. AB - A newborn male infant is presented with the characteristic phenotype of the cat eye syndrome and a small supernumerary chromosome shorter than a 22. He also had complete absence of parasympathetic ganglion cells throughout the small and large intestine. PMID- 2585463 TI - A single maxillary incisor as a manifestation of an ectodermal dysplasia. AB - A single, central, maxillary incisor was found in a patient with an ectodermal dysplasia. PMID- 2585465 TI - Unknown syndrome: congenital heart disease, ptosis, hypodontia, and craniosynostosis. AB - We report a child with total anomalous pulmonary venous drainage, ptosis, hypoplastic teeth, sagittal craniosynostosis, and developmental delay, together with several unusual features. PMID- 2585464 TI - Maternal translocation (9;18) with two abnormal offspring each with different chromosome derivatives. AB - We report a phenotypically normal woman with an apparently balanced reciprocal translocation between chromosomes 9 and 18 [46,XX,t(9;18)(p22;p11.2)], giving rise to unbalanced chromosome complements in two of her children, each of whom received a different derivative chromosome. The proband's karyotype is 46,XY, 18,+der(18), t(9;18)(p22;p11.2)mat, which results in a duplication of the distal portion of the short arm of chromosome 9 with a concomitant deletion of much of the short arm of chromosome 18. The karyotype of the proband's brother is 46, XY, 9,+der(9),t(9;18)(p22;p11.2)mat, which results in a deletion of the distal short arm of chromosome 9 and a duplication of most of the short arm of chromosome 18. The phenotype of each child is significantly different from that of his sib and is not consistent with any previously reported chromosome abnormality. PMID- 2585466 TI - Unknown syndrome in sibs: microcephaly, seizures, mental retardation, congenital heart disease, and skeletal abnormalities. AB - We present two male sibs with a series of malformations including microcephaly, mental retardation, congenital heart disease, skeletal abnormalities, micropenis, and mild hypothyroidism. Both have had seizures. While the pattern of abnormalities is similar to that previously reported in this journal as an unknown syndrome, the facies is clearly distinct, the hypothyroidism is mild, micropenis is present, and there are additional minor skeletal abnormalities. PMID- 2585467 TI - Updated results of the thalassaemia prevention programme carried out in Latium. PMID- 2585468 TI - Correlation of clinical and deletion data in Duchenne and Becker muscular dystrophy. AB - Cloned cDNA sequences representing exons from the Duchenne/Becker muscular dystrophy (DMD/BMD) gene were used for deletion screening in a population of 287 males males affected with DMD or BMD. The clinical phenotypes of affected boys were classified into three clinical severity groups based on the age at which ambulation was lost. Boys in group 1 had DMD, losing ambulation before their 13th birthday; those in group 2 had disease of intermediate severity, losing ambulation between the ages of 13 and 16 years; and boys in group 3 had BMD, being ambulant beyond 16 years. A fourth group consisted of patients too young to be classified. Clinical group allocation was made without previous knowledge of the DNA results. A gene deletion was found in 124 cases where the clinical severity group of the affected boy was known. The extent of the deletions was delineated using cDNA probes. There were 74 different deletions. Fifty-five of these were unique to individual patients, but the other 19 were found in at least two unrelated patients. The different clinical groups showed generally similar distributions of deletions, and the number of exon bands deleted (that is, deletion size) was independent of phenotype. Some specific deletion types, however, correlated with the clinical severity of the disease. Deletion of exons containing HindIII fragments 33 and 34 and 33 to 35 were associated with BMD and were not found in patients with DMD. Deletions 3 to 7 occurred in four patients with the intermediate phenotype and one patient with BMD. Other shared deletions were associated with DMD, although in four cases patients with disease of intermediate severity apparently shared the same deletion with boys with DMD. The range of phenotypes observed, and the overlap at the genetic level between severe and intermediate and mild and intermediate forms of dystrophy, emphasizes the essential continuity of the clinical spectrum of DMD/BMD. There were no characteristic deletions found in boys with mental retardation or short stature which differed from deletions in affected boys without these features. PMID- 2585469 TI - Diagnostic and counselling difficulties using a fully comprehensive screening protocol for families at risk for tuberous sclerosis. AB - Tuberous sclerosis (TS) results from an autosomal dominant gene which exhibits variable expression and reduced penetrance. Although there are well established diagnostic criteria for TS, examination of first degree relatives can cause diagnostic criteria for TS, examination of first degree relatives can cause diagnostic problems with consequent difficulties in genetic counselling. Using an extensive, non-invasive protocol consisting of skin examination with Wood's lamp, cranial CT scan, specialist ophthalmological and dental examination, skeletal survey, and echocardiography, we have examined 56 first degree relatives of persons with TS. These consisted of 40 parents and seven sibs from 25 sporadically affected families and nine persons from seven multigeneration families. In seven of the apparently sporadically affected families, three mothers had echocardiographical findings consistent with one or more rhabdomyoma. In another, the mother's renal ultrasound showed evidence of single cysts in both kidneys. In a fifth family, the father had suggestive but not diagnostic features of TS on the cranial CT scan and skeletal survey. In the sixth family, the mother was found to have atypical calcification on CT scan. In a seventh instance a sib from a two generation family had echocardiographical evidence of a rhabdomyoma. Even though the proband in three of the sporadically affected families presented with fits, developmental delay, and depigmented patches, and therefore did not strictly fulfil the diagnostic criteria for TS, two mothers were found to have evidence of rhabdomyomata on echocardiography and the brother of the third had typical depigmented patches. Although the presently accepted diagnostic criteria for TS may not allow one to make a definitive diagnosis of TS in these relatives, we recommend that an extensive screening protocol be used to examine first degree relatives and that caution be used in counselling apparently unaffected members of families at risk for TS. PMID- 2585470 TI - Fountain's syndrome: mental retardation, sensorineural deafness, skeletal abnormalities, and coarse face with full lips. PMID- 2585471 TI - Thanatophoric dysplasia in identical twins. PMID- 2585472 TI - The epidemiology of peritonitis caused by coagulase-negative staphylococci in continuous ambulatory peritoneal dialysis. AB - The epidemiology of 10 episodes of CAPD peritonitis caused by coagulase-negative staphylococci was studied. The infecting micro-organism was found in prospective skin swabs in six episodes, widely distributed and as the predominant, or equally predominant, organism at each site but was not detected in swabs taken more than 12 weeks before the episode of peritonitis; this suggests recent acquisition. Infecting strains were no more likely to be adherent or to produce slime than non infecting strains, nor had they any other characteristic detected in our typing scheme that might lead to their detection before peritonitis developed. PMID- 2585473 TI - Serum antibodies to giardial surface antigens: lower titres in persistent than in non-persistent giardiasis. AB - Antisera to two antigens of Giardia lamblia--plasma membrane (PM) protein and an affinity-purified surface antigen (SA56)--were raised in rabbits, and shown to agglutinate and kill trophozoites in vitro. These antibodies were also demonstrated by ELISA in the sera of paediatric patients with giardiasis. The titres of both antibodies were significantly higher in non-persistent (acute) and asymptomatic cases than in patients with persistent infection; and the latter group did not respond to anti-giardial therapy. The inability of this group to clear G. lamblia infection, in spite of therapy, may result from the low level of antibodies which mediate the killing of trophozoites. PMID- 2585474 TI - The susceptibility of germ-free, oestradiol-treated, mice to Mycoplasma hominis. AB - Conventionally reared female BALB/c mice, rendered susceptible to Mycoplasma hominis infection of the genital tract by treatment with oestradiol, have increased numbers of endogenous vaginal bacteria. The latter was reflected by the occurrence of bacterial growth in 95 (65.5%) of 145 cultures undertaken to isolate M. hominis from oestradiol-treated mice, but in only seven (4.8%) of 146 cultures from untreated animals. In addition, larger numbers of bacteria were seen in vaginal smears from oestradiol-treated mice than from untreated ones. Furthermore, abscesses developed in the genital region of 27 (17%) of 155 oestradiol-treated mice but in none of 50 that were untreated. However, such proliferation of the endogenous vaginal bacteria was not necessary for colonisation of the vagina by M. hominis. This was determined by showing that six germ-free, oestradiol-treated BALB/c mice given 2.5 x 10(5) ccu of M. hominis intravaginally became colonised vaginally for at least 14 days, with multiplication and spread of the organisms to the upper genital tract and elsewhere, whereas six similar untreated mice given the same inoculum remained uninfected. PMID- 2585476 TI - A method for measuring the various constituents of the human hair follicle. AB - Hair follicles from scalp biopsies (temporal and parietal regions) were isolated by microdissection. This technique allows preservation of the whole structure of the follicle in its fibrous sheath, or isolation of certain elements: bulb and dermal papilla. Each follicle is examined by transmission optical microscopy and its image is digitized into sixty-four grey levels by an image analyser. Follicle images are memorized on a hard disc, then recalled individually for measurement. The image analysis consists of thresholding, interactive selecting, then measurement of the following elements: diameter of the hair follicle, volume of the bulb, height of the keratogenous zone, mean diameter of the hair and size of the dermal papilla. These parameters were related to a clinical classification (terminal, dystrophic, vellus). This morphometric study constitutes an objective approach which is different from, but complementary, to the classic trichogram (telogen/anagen). PMID- 2585475 TI - Microcomputer system for ion microscopy digital imaging and processing. AB - Analytical ion microscopy is a powerful tool for biological tissue analysis as it allows direct chemical distribution imaging, even at low element concentrations. A microcomputer based digital imaging system achieving acquisition at low light level is presented. It includes a high sensitivity video camera connected to a specialized image processor subsystem. Acquired images consist of 512 x 512 pixels with 8 bits accuracy. Real-time image processing software has been implemented so that image processing may be performed on-line. Image processing software allows off-line image manipulation and correlation for biological interpretation of elemental mapping images. System capabilities are illustrated by a study of stable and radio iodine mapping in rat thyroid tissue. PMID- 2585477 TI - Health care workers' knowledge and attitudes concerning AIDS. AB - This paper reports the results of a study performed to address the many unresolved issues concerning health care workers and their treatment of patients with AIDS. A survey was developed to measure knowledge, attitudes and opinions, and other information of health care workers. The survey was administered to all employees of a 200 bed hospital. The authors provide a description of the study, indicating methods, subjects, and procedures. They report that the study identified problem areas in the educational/training of participants. According to the authors, the study indicates that there will be no AIDS-related staffing problems in health care organizations in the future. Additional findings concerning AIDS and health care workers are reported. PMID- 2585478 TI - Washington impressions. PMID- 2585479 TI - Cigarette smoking: more than a habit. AB - The author states that the pharmacologic and behavioral processes that determine nicotine addiction are similar to those that determine addiction to heroin and cocaine. He maintains that treatment of nicotine addiction should be more widely available, and suggests that many physicians still view cigarette smoking erroneously as a habit rather than a true drug addiction. PMID- 2585480 TI - Hospital emergency departments in Mississippi. AB - This paper is a descriptive study of hospital emergency departments in Mississippi. Hospital emergency departments are analyzed according to the number of patient visits per day and the services available. The data indicate that rapid access of a trauma patient to a high volume, broad service emergency department is difficult in much of the state. The authors encourage the state to utilize recommendations of the American College of Surgeons to develop a statewide emergency medical system. They maintain that such a system would better match existing resources with the needs of emergency patients. PMID- 2585481 TI - What is your medical practice worth? PMID- 2585482 TI - Structure of the goat psi beta y beta-globin pseudogene. Analysis of goat pseudogene evolutionary patterns. AB - The 12-member beta-globin gene locus of the goat contains three beta(adult)-type pseudogenes, one in each of three four-gene subsets of the locus. We have determined the complete nucleotide sequence of psi beta y, the pseudogene present in the most downstream four-gene subset, which also contains the functional fetal gene, beta F. psi beta y contains, throughout its length, numerous incapacitating mutations in common with the previously sequenced goat psi beta x and psi beta z pseudogenes consistent with the model that all were descended from a common pseudogene ancestor which became defective prior to the expansion of the beta globin locus in the goat lineage. Evolutionary analysis of the psi beta y sequence in comparison to psi beta x and psi beta z provides evidence that nucleotide substitutions were fixed in a random manner within these pseudogenes with respect to polarity, coding versus non-coding regions, and replacement sites versus silent sites. However, substitutions appear to have accumulated asymmetrically between different pseudogenes in a manner that provides evidence for partial gene conversion. Moreover, the presence of deletions in goat psi beta y, which are also observed in the cow pseudogene psi 2, but not in the cow psi 1 pseudogene, indicate that goat psi beta y and cow psi 2 are orthologous but cow psi 1 actually arose prior to the goat/cow divergence. The authentic goat orthologue to cow psi 1 temporarily existed in the goat lineage but was deleted, probably prior to the divergence of goats and sheep. PMID- 2585484 TI - Crystal structure of hexameric haemocyanin from Panulirus interruptus refined at 3.2 A resolution. AB - The use of non-crystallographic symmetry restraints in the refinement of the haemocyanin hexamer from Panulirus interruptus at 3.2 A resolution has resulted in a final model with a very reasonable geometry and a crystallographic R-factor of 20.1%, using 59,193 observed structure factor amplitudes between 8.0 and 3.2 A. The mean co-ordinate error is approximately 0.35 A. The six subunits appear to be related by symmetry operations that differ slightly from 32 point group symmetry. The six subunits have essentially maintained the same structure. The hexamer, with point group 32, is best described as a trimer of "tight dimers". The contacts between the subunits in such a dimer are more numerous, and better conserved during evolution than contacts in a trimer. The interface of a tight dimer is separated by an internal cavity into two "contact areas". The contact area nearest to the centre of the hexamer is most extensive and consists mainly of residues that are quite conserved among arthropodan haemocyanins. All these residues are provided by the second domain of each subunit. Hence, this second domain may play a crucial role in the allosteric functioning of this oxygen transport protein. The dinuclear copper oxygen-binding site resides in the centre of domain 2. This oxygen-binding centre is not fully accessible from the solvent. Three large cavities occur, however, within each subunit at the interfaces of the three domains. All three cavities contain ordered water molecules, and two of them are accessible from the surrounding solvent. These cavities may play a role in facilitating fast movement of dioxygen towards the binding site, which is situated in a highly conserved, rather hydrophobic core. A detailed definition of the geometry of the copper site is, of course, not possible at the limited resolution of 3.2 A. Nevertheless, it is possible to conclude that each copper is co-ordinated by two, more or less tightly bound, histidine ligands and one more distant histidine residue. The six histidine residues utilize their N epsilon atoms for copper co-ordination, while their N delta atoms are engaged in hydrogen bonds with conserved residues or water molecules. The two distant histidine ligands are located in apical positions and are on opposite sides with respect to the plane approximately defined by the four more tightly bound histidine ligands and the two copper ions. The copper-to-copper distance is 3.5 to 3.6 A in four of the subunits, but this distance deviates considerably in two others.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2585483 TI - Proteins binding to the liver-specific pyruvate kinase gene promoter. A unique combination of known factors. AB - A 183 base-pair fragment of the liver-specific promoter of the L-type puruvate kinase (L-PK) gene has been shown by transfection assay to be sufficient to confer a tissue-specific expression to a reporter gene. The proteins binding in vitro to this fragment have been investigated by a combination of DNase I footprinting, gel retardation of synthetic oligonucleotides and ultraviolet cross linking. Four proteins from liver nuclear extracts bind to the investigated fragment. They were called, from 3' to 5', L1 to L4 binding factors. The L1 site (nucleotides -95 to -66 with respect to the cap site) binds hepatocyte nuclear factor 1 (HNF1), a liver-specific protein. The L2 site (nucleotides -114 to -97) binds the ubiquitous nuclear factor 1 (NF1), or a related factor. The L3 site (nucleotides -144 to -126) binds liver factor A1 (LF-A1), another liver-specific protein. Finally, the L4 site (nucleotides -168 to -145) binds major late transcription factor (MLTF/USF/UEF), an ubiquitous protein. Each of these proteins has been detected in other liver-specific promoters, but their combination is unique to the liver-specific promoter of the L-PK gene. PMID- 2585486 TI - Crystallization and preliminary X-ray diffraction studies of an anti-4-hydroxy-3 nitrophenylacetic acid monoclonal antibody Fab fragment complexed with immunizing and heteroclitic haptens. AB - The Fab fragment of the anti-4-hydroxy-3-nitrophenylacetic acid monoclonal antibody, 88C6/12 has been crystallized in the presence of the eliciting hapten, 4-hydroxy-3-nitrophenacetyl-epsilon-aminocaproic acid (NP-aminocap) and the heteroclitic iodinated analog, 4-hydroxy-3-iodo-5-nitrophenylacetyl-epsilon aminocaproic acid (NIP-aminocap). Crystals obtained by precipitation with 32% (w/v) polyethylene glycol 3400 in the presence of 40 to 400 microM of either NP aminocap or NIP-aminocap, belong to the orthorhombic space group P2(1)2(1)2(1) with cell dimensions a = 81.2 A, b = 86.9 A, c = 131.1 A. The cell volume suggests the presence of two molecules of the complex per asymmetric unit. Analysis of the Patterson function indicates that these two molecules are related by a local 2-fold axis parallel to the crystallographic b axis located at x = 0.218 and z = 0.25. PMID- 2585487 TI - Preliminary analysis of crystals of satellite tobacco mosaic virus. AB - Satellite tobacco mosaic virus (STMV), a small T = 1 icosahedral plant virus, has been crystallized in a form suitable for high-resolution X-ray diffraction analysis. The crystals, which diffract to better than 2.5 A resolution, are of space group I222 and have unit cell dimensions of a = 176 A, b = 192 A and c = 205 A. The centers of the virus particles occupy 222 symmetry points in the unit cell and one quarter of the virus particle constitutes the asymmetric unit, which is therefore comprised of 15 capsid protein molecules. From packing considerations, the maximum diameter of the STMV particles cannot exceed 165 A, and it is probably 5 to 10 A less than this value. PMID- 2585485 TI - Crystallographic mapping of beta-lactams bound to a D-alanyl-D-alanine peptidase target enzyme. AB - X-ray crystallography has been used to examine the binding of three members of the beta-lactam family of antibiotics to the D-alanyl-D-alanine peptidase from Streptomyces R61, a target of penicillins. Cephalosporin C, the monobactam analog of penicillin G and (2,3)-alpha-methylene benzylpenicillin have been mapped at 2.3 A resolution in the form of acyl-enzyme complexes bound to serine 62. On the basis of the positions of these inhibitors, the binding of a tripeptide substrate for the enzyme, L-lysyl-D-alanyl-D-alanine, has been modeled in the active site. The binding of both inhibitors and substrate is facilitated by hydrogen-bonding interactions with a conserved beta-strand (297-303), which is antiparallel to the beta-lactam's acylamide linkage or the substrate's peptide bond. The active site is similar to that in beta-lactamases. PMID- 2585488 TI - Preliminary X-ray investigation of 70 S ribosome crystals from Thermus thermophilus. AB - Large three-dimensional crystals of 70 S from Thermus thermophilus have been grown from solutions of 2-methyl-2,4-pentanediol at 4 degrees C and examined in an X-ray synchrotron beam. The space group is P4(1)2(1)2 or P4(3)2(1)2 with unit cell dimensions of a = 510 A and c = 378 A. The diffraction patterns extend to better than 20 A. PMID- 2585489 TI - Preliminary crystallographic studies on human apo-lactoferrin in its native and deglycosylated forms. AB - Human apo-lactoferrin in both native and deglycosylated forms has been purified, and crystals obtained by dialysis against low ionic strength buffer solutions. The crystals of native apo-lactoferrin are orthorhombic, space group P2(1)2(1)2(1) with cell dimensions a = 222.0 A, b = 115.6 A, c = 77.8 A and have two protein molecules per asymmetric unit. Two crystal forms of deglycosylated apo-lactoferrin have been obtained. One is orthorhombic, space group P2(1)2(1)2(1), with cell dimensions a = 152.1 A, b = 94.6 A, c = 55.8 A. The second is tetragonal, space group I4, with cell dimensions a = b = 189.4 A, c = 55.1 A. Both of the latter have only one molecule per asymmetric unit, and are suitable for high-resolution X-ray structure analysis. PMID- 2585490 TI - Conservation of organization in the specificity polypeptides of two families of type I restriction enzymes. AB - We have identified the recognition sequence for the Citrobacter freundii restriction endonuclease CfrA, a member of the A-family of type I R-M enzymes. This bipartite target sequence differs in both its components from those of other type I enzymes. We determined the nucleotide sequence of its specificity gene (hsdS) and a comparison of this with its relative EcoA identifies two extensive variable regions, an organization analogous to that found in the K-family of type I R-M enzymes. The specificity polypeptides of the A-family, unlike those of K, have an N-terminal conserved region, and this includes a sequence repeated within the central conserved region. A second repeat sequence, identified at the amino acid level, coincides with the only sequence similarity common to all type I S polypeptides. Sequences immediately downstream from the hsdS genes of EcoA, CfrA, EcoK, B and D are almost identical, consistent with an allelic chromosomal location. PMID- 2585491 TI - Complementation of in vitro-assembled spliceosomes. AB - We describe the development and application of a system of in vitro-assembled splicing complexes that can be used for the identification of protein splicing factors which become associated with the spliceosome at the end of the assembly process ("late" splicing components). A splicing reaction performed in the presence of polyvinyl alcohol is interrupted after 15 to 20 minutes, before the appearance of splicing intermediates and products in significant amounts. Following low-speed centrifugation, a pellet is obtained containing splicing complexes that can be solubilized with 0.6 M-KCl. These complexes can be rapidly complemented for splicing in the presence of ATP and Mg2+ with protein factors that are present in HeLa cell nuclear extracts or in chromatographic extract fractions. Biochemical features of the complementation reactions, and conditions for reversible uncoupling of the two splicing steps, are described and discussed. These conditions are used to generate fully assembled spliceosomes in which splicing of the pre-mRNA can occur in the presence of ATP and Mg2+, but in the absence of nuclear extract ("autonomous splicing"). PMID- 2585492 TI - Plasmid-partition functions of the P7 prophage. AB - The sequences responsible for the proper partition of the P7 plasmid prophage to daughter cells lie within a discrete block of non-similarity between P7 and its close relative P1. The DNA sequence of the P7 region was determined. A segment with near identity to the replication (rep) region of P1 is followed by sequences (P7 par) that are clearly related to but very divergent from the P1 partition region. Subcloning was used to define the ends of the functional P7 partition region. It begins with a transcription promoter followed by two large open reading frames, parA and parB, that overlap by a single base and are read in the same direction. The genes direct the synthesis of two proteins, P7 ParA and ParB, with apparent Mr of 44,000 and 37,000. Specific frameshift mutations were introduced into the two genes. Each mutation blocked plasmid partition and both were complemented when the P7 ParA and ParB proteins were supplied in trans. The amino acid sequences of the P7 proteins show strong similarities to the P1 ParA and ParB proteins. However, the DNA sequences of the P7 and P1 open reading frames are remarkably divergent, largely caused by variability at the third positions in the codons. Interspecific complementation tests showed that the P7 proteins are unable to complement P1 parA or parB mutants, and the P1 proteins fail to complement the P7 mutations. Downstream from the P7 parB open reading frame is a sequence that conserves 27 of the 34 base-pairs of the P1 partition site parS. Unlike the P1 parS site, the P7 equivalent does not contain as extensive an inverted repeat. The heptamer sequences that define ParB binding sites within P1 parS are represented in P7 but differ from it by one base. A related sequence that coincides with the secondary ParB binding site within the P1 incB sequences is present nearby. Other sequences within the P7 incB region are rather different from their P1 counterparts. The basis for the major differences in specificity of the P1 and P7 par components is discussed. Comparison of the P1 and P7 sequences, and the nature of the junctions between similar and different sequences, suggest that the phages could have evolved by the pickup of divergent cassettes by recombination. PMID- 2585493 TI - Assembly of hybrid RNAs with tobacco mosaic virus coat protein. Evidence for incorporation of disks in 5'-elongation along the major RNA tail. AB - We have shown that during the reassembly of tobacco mosaic virus (TMV) RNA, with the coat protein supplied as a "disk preparation", the lengths of RNA protected from nuclease are "quantized" with steps which correspond to incorporation of the subunits from either a single or, more commonly, both rings of a disk. This interpretation has been challenged and it was suggested that the pattern was due to special, though unspecified features of the sequence of TMV RNA. To test whether the specific sequence of TMV RNA is important during the elongation, rather than just during nucleation, we have now followed growth of particles containing hybrid RNAs, with the TMV RNA origin of assembly but otherwise non-TMV sequences. We have prepared in vitro RNA transcripts containing heterologous RNA 5' to the origin of assembly sequence from TMV RNA, i.e. with a heterologous RNA tail in place of the natural major 5'-tail and no minor tail, and used these for assembly experiments. In each case we observe a banding pattern very similar to that which we had found with native TMV RNA and with a dominant quantum step of just over 100 bases, and sometimes also a step of 50 bases, strongly suggesting that this is not due to any feature of the TMV RNA. This same repeat is also visible even with a heterologous RNA chosen because it had a sequence repeat of 135 or 136 bases, confirming that the quantization is due to a feature of the elongation reaction and in no way to the RNA sequence being encapsidated. We have also followed elongation with the origin of assembly located 5' to the heterologous RNA. This leads to a slower elongation along this 3'-tail, after the initial rapid encapsidation of the origin RNA, which lacks any quantization of length protected. These results are fully compatible with the hypothesis we had advanced earlier, that the major growth along the 5'-tail is from performed aggregates ("disks") while the minor growth along the 3'-tail is from subunits in the "A-protein" adding singly or a few at a time. PMID- 2585494 TI - Orientation of the bases of single-stranded DNA and polynucleotides in complexes formed with the gene 32 protein of bacteriophage T4. A linear dichroism study. AB - Linear dichroism measurements were performed in the wavelength region 250 to 350 nm on complexes between the single-stranded DNA binding protein of bacteriophage T4 (gp32) and single-stranded DNA and a variety of homopolynucleotides in compressed polyacrylamide gels. The complexes appeared to orient well, giving rise to linear dichroism spectra that showed contributions from both the protein aromatic residues and the bases of the polynucleotides. In most cases the protein contribution appeared to be very similar, and the linear dichroism of the bases could be explained by similar orientations of the bases for most of the complexes. Assuming a similar, regular structure for most of the polynucleotides in complex, only a limited set of combinations of tilt and twist angles can explain the linear dichroism spectra. These values of tilt and twist are close to (-40 degrees, 30 degrees), (-40 degrees, 150 degrees), (40 degrees, -30 degrees) or (40 degrees, -150 degrees), with an uncertainty in both angles of about 15 degrees. Although the linear dichroism results do not allow a choice between these possible orientations, the latter two combinations are not in agreement with earlier circular dichroism calculations. For the complexes formed with poly(rC) and poly(rA), the linear dichroism spectra could not be explained by the same base orientations. In these two cases also the protein contribution to the linear dichroism appeared to be different, indicating that for some aromatic residues the orientations are not the same as those in the other complexes. The different structures of these complexes are possibly related to the relatively low binding affinity of gp32 to poly(rC), and to a lesser extent to poly(rA). PMID- 2585495 TI - An alpha-helical peptide model for electrostatic interactions of proteins with DNA. The N terminus of RecA. AB - A series of synthetic peptides have been studied as models for non-specific protein-DNA interactions. In an alpha-helical conformation, the charged amino acid residues of the N-terminal 24 residues of RecA protein are asymmetrically distributed; at neutral pH there is a +4 charge on one face of the helix and a -3 charge on the other face. Modeling suggests that the positive face of the helix can bind five DNA phosphate groups by electrostatic interactions. Circular dichroism (c.d.) spectra indicate that the analogous peptide, Rec24 (AIDENKQKALAAALGQIEKQFGKG-amide), is largely unstructured in water but becomes highly helical in the presence of DNA. Peptide titrations of fluorescent etheno DNA confirm that the changes in the c.d. spectrum of the peptide are associated with binding, although a dependence of the c.d. signal on the degree of DNA saturation is observed, indicating that peptide can be bound in more than one conformation. At saturation the peptide binds to 5.0(+/- 0.5) DNA phosphate groups as predicted and the electrostatic nature of the binding is confirmed by a strong dependence on salt concentration. A "mutant" peptide where an acidic glutamate residue replaces an alanine on the basic face of the Rec24 helix exhibits weaker binding to single-stranded DNA, also consistent with the electrostatic nature of the proposed peptide-DNA interaction. Extending Rec24 by ten amino acid residues, where the additional residues do not participate in the helical motif, does not noticeably affect binding. Thus, we show experimentally that an asymmetric charge distribution on an alpha-helix can represent an important element for binding nucleic acids. PMID- 2585496 TI - Comparison of the refined crystal structures of two wheat germ isolectins. AB - The crystal structures of two closely related members of the multigene family of wheat lectins (isolectins 1 and 2) have been compared. These isolectins differ at five sequence positions, one being located in the saccharide binding site modulating ligand affinity. Crystals of the two isolectins are closely isomorphous (space group C2). The atomic models are based on structure refinement at 1.8 A resolution in the case of isolectin 2 (WGA2) and 2.0 A resolution in the case of isolectin 1 (WGA1). Refinement results for WGA1, recently completed with a crystallographic R-factor of 16.5% (Fo greater than 3 sigma (Fo)), are presented. Examination of a difference Fourier map, [FWGA2-FWGA1], at 2.0 A resolution and direct superposition of the two models indicated an overall close match of the two structures. Local differences are observed in the region of residues 44 to 69, where three sequence differences occur, and at highly mobile external residues on the surface. The average positional discrepancy (root-mean square delta r) for corresponding protein atoms in the two crystal structures is 0.64 A for independent protomer I and 0.61 A for protomer II (0.29 A and 0.30 A for main-chain atoms). The mean atomic temperature factors are very similar 20.9 versus 22.0 A2). Regions of high flexibility coincide in the two isolectin structures. Of the 210 water sites identified in WGA1, 144 have corresponding positions in WGA2. A set of 51 well-ordered sites was found to be identical in the two independent environments in both structures, and was considered to be important for structure stabilization. Both of the unique sugar binding sites superimpose very closely, exhibiting root-mean-square positional differences ranging from 0.29 A to 0.42 A. The side-chains of the critical tyrosine residues, Tyr73 (P-site) and Tyr159 (S-site), superimpose best, while other highly flexible aromatic groups (Tyr64 and Trp150) and several water sites display large differences in position (0.5 to 1.0 A) and high temperature factors. The aromatic side-chains of Tyr66 in WGA1 and His66 in WGA2 are oriented similarly. PMID- 2585497 TI - Spectral properties unique to the myoglobins lacking the usual distal histidine residue. AB - Myoglobins can be divided into two groups. One group contains the usual myoglobins that have histidine at the distal (E7) position, and the other contains a few, but interesting myoglobins that lack the usual distal histidine residue. Spectroscopic examinations have shown that there is a remarkable difference in the Soret band between the two types of myoglobin, and an absorbance ratio of the Soret peak of the acidic met-form to that of the oxy-form seems to be very useful as a simple criterion for predicting whether or not a myoglobin has the usual distal histidine residue. PMID- 2585498 TI - Characterization of the long terminal repeats of micropia elements microdissected from the Y-chromosomal lampbrush loops "threads" of Drosophila hydei. AB - Four micropia elements from Drosophila melanogaster and D. hydei have been analysed by sequencing. Two elements, from D. hydei, micropia-DhMiF8 and -DhMiF2, were recovered by cloning microdissected Y-chromosomal lampbrush loops "threads". This method allows isolation of repetitive sequences from defined chromosomal positions, but recovery of large and overlapping inserts is difficult. In case of the Y-chromosomal micropia elements it was not possible to define the endpoints of their long terminal repeat sequences precisely. Comparison of these locus defined micropia elements to complete micropia elements isolated from D. melanogaster allowed identification of micropia-DhMiF8 and micropia-DhMiF2 long terminal repeats (LTRs). LTR sequences from the two Drosophila species are not conserved except for a few short sequences found at comparable positions that are believed to have functional significance. In contrast, the Leu-tRNA primer binding site and plus strand primer binding site are conserved between D. melanogaster and D. hydei. PMID- 2585500 TI - Organization of the immunity region immI of bacteriophage P1 and synthesis of the P1 antirepressor. AB - The immI region of bacteriophage P1 includes the ant/reb gene, which encodes the antirepressor protein, and the c4 gene, which encodes a repressor molecule that negatively regulates antirepressor synthesis. The antirepressor interferes with the activity of the P1 repressor of lytic function, the product of the c1 gene. We have determined the DNA sequences of the immI region of P1 wild-type and the mutants virs, ant16, ant17, and reb22. Using suitable P1 immI DNA subfragments cloned into a vector of the T7 bacteriophage RNA polymerase expression system the antirepressor protein(s) was overproduced. On the basis of positions of immI mutations and the sizes of ant gene products, the following organizational feature of the P1 immI region is suggested: (1) the genes c4 and ant are cotranscribed in that order from the same promoter in the clockwise direction of the P1 genetic map; (2) an open reading frame for an unknown gene is located in between c4 and ant; (3) the site at which the c4 repressor acts is located within the c4 structural gene; (4) two antirepressor proteins of molecular weights 42,000 and 32,000 are encoded by a single open reading frame, with the smaller protein initiating at an in-frame start codon; (5) transcription of immI is regulated via a c1-controlled operator, Op51, indicating a communication between the immunity systems immC and immI. PMID- 2585499 TI - Genes, variant genes and pseudogenes of the human tRNA(Val) gene family. Expression and pre-tRNA maturation in vitro. AB - Nine different members of the human tRNA(Val) gene family have been cloned and characterized. Only four of the genes code for one of the known tRNA(Val) isoacceptors. The remaining five genes carry mutations, which in two cases even affect the normal three-dimensional tRNA structure. Each of the genes is transcribed by polymerase III in a HeLa cell nuclear extract, but their transcription efficiencies differ by up to an order of magnitude. Conserved sequences immediately flanking the structural genes that could serve as extragenic control elements were not detected. However, short sequences in the 5' flanking region of two genes show striking similarity with sequences upstream from two Drosophila melanogaster tRNA(Val) genes. Each of the human tRNA(Val) genes has multiple, i.e. two to four, transcription initiation sites. In most cases, transcription termination is caused by oligo(T) sequences downstream from the structural genes. However, the signal sequences ATCTT and CTTCTT also serve as effective polymerase III transcription terminators. The precursors derived from the four tRNA(Val) genes coding for known isoacceptors and those derived from two mutant genes are processed first at their 3' and subsequently at their 5' ends to yield mature tRNAs. The precursor derived from a third mutant gene is incompletely maturated at its 3' end, presumably as a consequence of base-pairing between 5' and 3' flanking sequences. Finally, precursors encoded by the genes that carry mutations affecting the tRNA tertiary structure are completely resistant to 5' and 3' processing. PMID- 2585501 TI - Molecular basis of spontaneous mutation at the aprt locus of hamster cells. AB - Mutations occurring spontaneously at the hamster aprt locus were examined at the base-pair level by amplifying target sequences using the polymerase chain reaction and then directly sequencing the double-stranded products. In a collection of 89 sequenced genes, all types of mutations were found, with transitions (mostly G.C to A.T) constituting the largest class (35%), transversions accounting for 27%, and small deletions/duplications for 25%. Simple base substitutions were distributed throughout the aprt structural gene with few sites having recurring mutations and G.C base-pairs being the predominant substitution target. Small deletions, on the other hand, were not distributed so evenly, being concentrated in a region of aprt rich in short direct and inverted repeat sequences. The base substitutions were predominantly missense, while about 10% produced nonsense codons. Splice junctions, and start and stop codons were also significant targets for mutation. No alterations were detected in three aprt-deficient strains after sequencing all exons and substantial upstream and downstream regions. PMID- 2585502 TI - Single base mismatches in DNA. Long- and short-range structure probed by analysis of axis trajectory and local chemical reactivity. AB - We have devised a procedure to generate any single base mismatch in a constant sequence context, and have studied these from two points of view. (1) We have examined electrophoretic mobility of 458 base-pair fragments containing approximately centrally located single mismatches, in polyacrylamide gels, compared to fully matched DNA fragments. We found that no single mismatch caused a significant perturbation of gel mobility, and we conclude that all the mismatches may be accommodated within a helical geometry such that there is no alteration of the path of the helix axis in a straight DNA molecule. (2) We have studied all the single mismatches with respect to reactivity to a number of chemical probes. We found that: (a) No mispaired adenine bases are reactive to diethyl pyrocarbonate and are therefore not simply unpaired such that N-7 is exposed. (b) A number of mispaired thymine bases are reactive to osmium tetroxide, and cytosine bases to hydroxylamine. (c) Where crystal or nuclear magnetic resonance structures are available, the reactivity correlates with exposure of the pyrimidine 5,6 double bonds to attack in the major groove as a result of wobble base-pair formation. This is particularly clear for G.T and I.T base-pairs. (d) Reactivity of bases in mismatched pairs can be dependent on sequence context. (e) Reactivity of the C.C mismatch to hydroxylamine is suppressed at low pH, suggesting that a rearrangement of base-pairing occurs on protonation. The results overall are consistent with the formation of stacked intrahelical base-pairs wherever possible, resulting in no global distortion of the DNA structure, but specific enhancement of chemical reactivity in some cases. PMID- 2585503 TI - Cloning, over-expression and the catalytic properties of the EcoP15 modification methylase from Escherichia coli. AB - The EcoP15 modification methylase gene from the p15B plasmid of Escherichia coli 15T-has been cloned and expressed at high levels in a plasmid vector system. We have purified the enzyme to near homogeneity in large amounts and have studied some of its enzymatic properties. Initial rates of methyl transfer are first order in methylase concentration and, with pUC19 DNA as substrate, the reaction proceeds by a random mechanism in which either DNA or S-adenosylmethionine can bind to the free enzyme. After methyltransfer to DNA, the methylated DNA and S adenosylhomocysteine appear to dissociate in random order. As expected in such a mechanism, S-adenosylhomocysteine is a non-competitive inhibitor by S adenosylmethionine at concentrations not much above its KM suggests that release of methylated DNA may be the rate-limiting step. This suggestion is strengthened by the fact that a mutant of the closely related EcoP1 does not show such substrate inhibition. PMID- 2585504 TI - The transverse location of the retinal chromophore in the purple membrane by diffusion-enhanced energy transfer. AB - We have used fluorescence energy transfer in the rapid-diffusion limit (RDL) to estimate the trans-membrane depth of retinal in the purple membrane (PM). Chelates of Tb(III) are excellent energy donors for the retinal chromophore of PM, having a maximum Ro value for Forster energy transfer of approximately 62 A (assuming a donor quantum yield of 1). Energy transfer rates were measured from the time-resolved emission kinetics of the donor. The distance of closest approach between chelates and the chromophore was estimated by simulating RDL energy-transfer rate constants according to geometric models of either PM sheets or membrane vesicles. The apparent rate constant for RDL energy transfer between Tb(III)HED3A and retinal in PM sheets is 1.5(+/- 0.1) x 10(6) M-1 s-1, corresponding to a depth of approximately 10 +/- 2 A for the retinal chromophore. Cell envelope vesicles (CEVs) from Halobacterium halobium were studied by using RDL energy transfer to assess the proximity of retinal to either the extracellular or intracellular face of the PM. The estimated depth of retinal from the extravesicular face of the PM is 10 +/- 3 A, based on the RDL energy transfer rate constant. Energy-transfer levels to retinal in the PM were estimated by an indirect method with energy donors trapped in the inner-aqueous space of CEVs. The rate constants derived for this arrangement are too low to be consistent with the shortest depth of retinal deduced for PM sheets. Thus, the intravesticular face of CEVs, corresponding to the cytoplasmic face of cells, is the more distant surface from the chromophore of bacteriorhodopsin. PMID- 2585505 TI - ATP-induced structural change in myosin subfragment-1 revealed by the location of protease cleavage sites on the primary structure. AB - To understand the nature of the ATP-induced structural change in myosin subfragment-1, rabbit and chicken skeletal subfragments-1s were cleaved by various proteolytic enzymes in the absence, and in the presence, of ATP and the exact locations of the cleavage sites that were affected by ATP were determined from the amino end analysis of fragments by the use of a protein sequencer. It was found that subtilisin cleaved a site between Gln27 and Asn28 of rabbit subfragment-1 and between Gln28 and Asn29 of chicken subfragment-1 only in the presence of ATP. Thermolysin cleaved a site between Pro31 and Phe32 of chicken subfragment-1 in the presence of ATP, but the same site of rabbit subfragment-1 was not cleaved. The location of these sites is quite similar to the ATP-induced chymotryptic cleavage site of chicken gizzard heavy meromyosin, between Trp29 and Ser30 as reported by others. It is suggested, therefore, that the structure and the ATP-induced structural change in the regions are similar in these subfragment 1s. ATP also changes the cleavage rate of the 26K-50K junction by many proteases. Exact cleavage sites were determined and the relationship between their location and the suppression or the enhancement by ATP of the cleavage was studied. It was found that the cleavage sites were restricted to a quite narrow region and only the cleavage by thermolysin that attacked the middle of the region was enhanced by ATP. The distribution of the cleavage sites and the effect of ATP suggest that ATP induces drastic structural change at the middle of the 26K-50K junction region. The region attacked easily by many proteases coincided very well with a hydrophilic region indicated by the hydropathy index. The region probably protrudes outside and is, therefore, easily attacked by many proteases. PMID- 2585506 TI - Structure of human lactoferrin: crystallographic structure analysis and refinement at 2.8 A resolution. AB - The structure of human lactoferrin has been refined crystallographically at 2.8 A (1 A = 0.1 nm) resolution using restrained least squares methods. The starting model was derived from a 3.2 A map phased by multiple isomorphous replacement with solvent flattening. Rebuilding during refinement made extensive use of these experimental phases, in combination with phases calculated from the partial model. The present model, which includes 681 of the 691 amino acid residues, two Fe3+, and two CO3(2-), gives an R factor of 0.206 for 17,266 observed reflections between 10 and 2.8 A resolution, with a root-mean-square deviation from standard bond lengths of 0.03 A. As a result of the refinement, two single-residue insertions and one 13-residue deletion have been made in the amino acid sequence, and details of the secondary structure and tertiary interactions have been clarified. The two lobes of the molecule, representing the N-terminal and C terminal halves, have very similar folding, with a root-mean-square deviation, after superposition, of 1.32 A for 285 out of 330 C alpha atoms; the only major differences being in surface loops. Each lobe is subdivided into two dissimilar alpha/beta domains, one based on a six-stranded mixed beta-sheet, the other on a five-stranded mixed beta-sheet, with the iron site in the interdomain cleft. The two iron sites appear identical at the present resolution. Each iron atom is coordinated to four protein ligands, 2 Tyr, 1 Asp, 1 His, and the specific Co3(2 ), which appears to bind to iron in a bidentate mode. The anion occupies a pocket between the iron and two positively charged groups on the protein, an arginine side-chain and the N terminus of helix 5, and may serve to neutralize this positive charge prior to iron binding. A large internal cavity, beyond the Arg side-chain, may account for the binding of larger anions as substitutes for CO3(2 ). Residues on the other side of the iron site, near the interdomain crossover strands could provide secondary anion binding sites, and may explain the greater acid-stability of iron binding by lactoferrin, compared with serum transferrin. Interdomain and interlobe interactions, the roles of charged side-chains, heavy atom binding sites, and the construction of the metal site in relation to the binding of different metals are also discussed. PMID- 2585507 TI - Molecular packing in profilin: actin crystals and its implications. AB - Analysis of profilin: actin crystals reveals an extensive intermolecular network, rather than a discrete "monomeric complex", comprising stacked actin ribbons held in place by columns of profilin molecules, wedged in between neighboring actin subunits and running perpendicular to the ribbons. Comparison with data from electron microscopy, X-ray diffraction, spectroscopy, and biochemistry of actin suggests that a simple transformation relates the ribbon to f-actin. The crystals exhibit unusual polymorphic properties, which strengthens the view that movements within the actin monomer are important for force generation. PMID- 2585508 TI - Nuclear magnetic resonance studies of flexible opiate conformations at monoclonal antibody binding sites. Quantitative interproton distances obtained from comparing theoretical and experimental transferred nuclear Overhauser enhancement: correlation with antibody sequence. AB - A previous publication described the use of qualitative intramolecular 1H transferred nuclear Overhauser effect measurements to determine the conformations of flexible ligands at monoclonal anti-opiate antibody binding sites. This paper concentrates on the quantitative interpretation of experiments of this type using the ligand nalorphine (N-allyl morphine) and a single anti-opiate monoclonal antibody. I compare the experimental unidimensional driven nuclear Overhauser effect buildup curves to theoretical curves derived with a knowledge of the fixed interproton distances in the ligand. The discussion covers the potential accuracies of derived distances and concentrates on two problem areas associated with determining structures from this type of experiment. The most serious one is the case where, because of particular multiproton spatial distributions, spin diffusion is so rapid that it cannot be determined experimentally and where numerical fits of theoretical calculations are misleading. The results show that, while intraligand spin diffusion complicates the interpretation for some proton pairs, with many others accuracies within about 0.3 A for interproton distances from 2 to 4 A are attainable. The results confirm the earlier report that the conformation of nalorphine in this antibody binding site differs from the major one present in solution or in the crystal. An important aspect of the work is that theoretical prediction of nuclear Overhauser effect time-dependence is an important practical tool for recognizing cases where interpretation of experiments will be difficult. Initial data on protein-to-ligand transferred nuclear Overhauser effect are presented, which show that at least one aromatic amino acid residue is closely involved in the binding of the ligand. The companion paper presents the primary sequences of the variable regions of the antibodies being used in our studies. In this paper, these and associated immunochemical studies are correlated with the nuclear magnetic resonance results. The combination of data presented in the two papers provides a basis for future work on protein-ligand interproton distances in the range 1 to 5 A using both transferred nuclear Overhauser effect (for rapidly exchanging ligands) and isotope-edited, indirectly detected nuclear Overhauser effect (for tightly bound ligands). PMID- 2585509 TI - Crystal structure of recombinant human interleukin-1 beta at 2.0 A resolution. AB - The crystal structure of recombinant human interleukin-1 beta (IL-1 beta) has been determined at 2.0 A resolution and refined to a crystallographic R-factor of 0.19. Three heavy-atom derivatives were identified and used for multiple isomorphous replacement phasing. Interpretation of the resulting electron density map revealed a structure in which there are 12 antiparallel beta-strands and no alpha-helix. The single 153-residue polypeptide chain is folded into a six stranded beta-barrel similar in architecture to the Kunitz-type trypsin inhibitor found in soybeans. The molecule displays approximate 3-fold symmetry about the axis of the beta-barrel. Each successive pair of component strands of the barrel brackets an extensive sequence outside the barrel that includes an additional pair of beta-strands and a prominent loop. Together, these three external segments conceal much of the perimeter and one end of the barrel, leaving only the end supporting the chain termini fully exposed. The structure can be used to identify portions of the polypeptide chain that are exposed on the surface of the molecule, some of which must be epitopes recognized by interleukin-1 beta receptors. PMID- 2585511 TI - Thermodynamics of amide hydrogen bond formation in polar and apolar solvents. AB - We present the initial findings of a theoretical study of hydrogen bond formation between two formamide molecules in water and in carbon tetrachloride. These systems were chosen as the simplest models for secondary structure formation in the polar environment near the protein surface and the apolar environment of the protein interior. We have employed thermodynamic simulation methods to obtain absolute binding free energies and free energy profiles for the formation of peptide hydrogen bonds in the two solvents. We find that the amide hydrogen bond is stable by 8.4 kcal/mol in CCl4, and by 0.3 kcal/mol in water. Our results indicate also that the hydrogen-bonded dimer is 2.2 kcal/mol more stable in water than it is in CCl4. We compare our results with those from experiment, and discuss their use in interpreting mechanisms of protein folding. PMID- 2585510 TI - Role of the hydrophobic effect in stability of site-specific protein-DNA complexes. AB - The site-specific binding interaction of lac repressor with a symmetric operator sequence and of EcoRI endonuclease with its specific recognition site both exhibit a characteristic dependence of equilibrium binding constant (Kobs) on temperature, in which Kobs attains a relative maximum in the physiologically relevant temperature range. This behavior, which appears to be quite general for site-specific protein-DNA interactions, is indicative of a large negative standard heat capacity change (delta C0P,obs) in the association process. By analogy with model compound transfer studies and protein folding data, we propose that this delta C0P,obs results primarily from the removal of non-polar surface from water in the association process. From delta C0P,obs we obtain semiquantitative information regarding the change in water-exposed non-polar surface area (delta Anp) and the corresponding hydrophobic driving force for association (delta G0hyd): delta G0hyd approximately equal to 8(+/- 1) x 10(1) delta C0P,obs approximately equal to -22(+/- 5) delta Anp. We propose that removal of non-polar surface from water (the hydrophobic effect) and release of cations (the polyelectrolyte effect) drive the thermodynamically unfavorable process (e.g. conformational distortions) necessary to achieve mutually complementary recognition surfaces (at a steric and functional-group level) in the specific complex. PMID- 2585512 TI - Intermolecular contacts within sickle hemoglobin fibers. AB - By combining X-ray crystallographic co-ordinates of sickle hemoglobin (HbS) molecules with three-dimensional reconstructions of electron micrographs of HbS fibers we have synthesized a model for the structure of the clinically relevant HbS fiber. This model largely accounts for the action of 55 point mutations of HbS whose effect on fiber formation has been studied. In addition, it predicts locations at which additional point mutations are likely to affect fiber formation. The number of intermolecular axial contacts decreases with radius until, at the periphery of the fiber, there are essentially no axial contacts. We suggest that this observation accounts for the limited radial growth of the HbS fiber and that a similar mechanism may be a factor in limiting the size of other helical particles. The methodology for the synthesis of the fiber model is applicable to other systems in which X-ray crystallographic and electron microscopic data are available. PMID- 2585513 TI - Myosin crossbridge orientation in demembranated muscle fibres studied by birefringence and X-ray diffraction measurements. AB - Muscle contraction is generally thought to involve changes in the orientation of myosin crossbridges during their ATP-driven cyclical interaction with actin. We have investigated crossbridge orientation in equilibrium states of the crossbridge cycle in demembranated fibres of frog and rabbit muscle, using a novel combination of techniques: birefringence and X-ray diffraction. Muscle birefringence is sensitive to both crossbridge orientation and the transverse spacing of the contractile filament lattice. The latter was determined from the equatorial X-ray diffraction pattern, allowing accurate characterization of the orientation component of birefringence changes. We found that this component decreased when relaxed muscle fibres were put into rigor at rest length, and when either the ionic strength or temperature of relaxed fibres was lowered. In each case the birefringence decrease was accompanied by an increase in the intensity of the (1,1) equatorial X-ray reflection relative to that of the (1,0) reflection. When fibres that had been stretched largely to eliminate overlap between actin- and myosin-containing filaments were put into rigor, there was no change in the orientation component of the birefringence. When isolated myosin subfragment-1 was bound to these rigor fibres, the orientation component of the birefringence increased. The birefringence changes at rest length are likely to be due to changes in the orientation of myosin crossbridges, and in particular of the globular head region of the myosin molecules. In relaxed fibres from rabbit muscle, at 100 mM ionic strength, 15 degrees C, the long axis of the heads appears to be relatively well aligned with the filament axis. When fibres are put into rigor, or the temperature or ionic strength is lowered, the degree of alignment decreases and there is a transfer of crossbridge mass towards the actin containing filaments. PMID- 2585515 TI - Glycera dibranchiata hemoglobin. Structure and refinement at 1.5 A resolution. AB - The coelomic cells of the common marine bloodworm Glycera dibranchiata contain several hemoglobin monomers and polydisperse polymers. We present the refined structure of one of the Glycera monomers at 1.5 A resolution. The molecular model for protein and ordered solvent for the deoxy form of the Glycera monomer has been refined to a crystallographic R-factor of 12.7% against an X-ray diffraction dataset at 1.5 A resolution. The positions of 1095 protein atoms have been determined with a maximum root-mean-square (r.m.s.) error of 0.13 A, and the r.m.s. deviation from ideal bond lengths is 0.015 A and from ideal bond angles is 1.0 degree. The r.m.s. deviation of planar groups from their least-squares planes is 0.007 A, and the r.m.s. deviation for torsion angles is 1.2 degrees for peptide groups and 16.8 degrees for side-chains. A total of 153 water molecules has been located, and they have been refined to a final average occupancy of 0.80. Multiple conformations have been found for five side-chains, and a change has been suggested for the sequence at five residues. The heme group is present in the "reverse" orientation that differs only in the positions of the vinyl beta carbons from the "normal" orientation. The doming of the heme towards the proximal side, and the bond distances and angles of the heme and proximal histidine are typical of most deoxy globin structures. The substitution of leucine for the distal histidine residue (E7) creates an unusually hydrophobic heme pocket. PMID- 2585514 TI - Primary structure of the silk fibroin light chain determined by cDNA sequencing and peptide analysis. AB - A cDNA clone, pFL18, carrying a putative full-length fibroin light chain (L chain) sequence was isolated and its nucleotide sequence was determined. This revealed the presence of an open reading frame corresponding to a polypeptide with 262 amino acid residues. The sequence was concluded to be that of the L chain with its signal peptide because corresponding amino acid sequences for the seven tryptic and the four chymotryptic peptides from the purified L-chain were all included and an N-terminal region having typical properties of a signal peptide was present. The N terminus of the mature form of L-chain was identified as N-acetyl serine by analyzing the acyl-dansylhydrazide derived from the N-acyl amino acid which had been released from the N-terminal blocked chymotryptic peptide by the acylamino acid-releasing enzyme. It was suggested that a signal peptide had cleaved between Pro18 and Ser19, yielding a mature L-chain polypeptide consisting of 244 amino acid residues. The molecular weight of the L chain was calculated to be 25,800 including the N-acetyl group. The L-chain contained three Cys residues, two of which were suggested to form an intramolecular disulfide linkage, leaving the third one at the most C-terminal position and in a relatively hydrophilic region as the most probable site of disulfide linkage with the fibroin heavy chain. PMID- 2585517 TI - 1H and 31P nuclear magnetic resonance studies of the differences in DNA deformation induced by anti-tumoral 7H-pyrido[4,3-c]carbazole dimers. AB - Ditercalinium (2,2'-[( 4,4'-bipiperidine]-1,1'-diyldi-2,1-ethane-diyl) bis-[10 methoxy-7H pyrido[4,3-c]carbazolium)tetramethane sulfonate (NSC 366241], a DNA bis-intercalating compound, is a potent anti-tumoral rigid dimer. Previous studies have shown that a reduced flexibility of the linking chain of such a dimer is essential for its biological activity. In order to understand, at the molecular level, the mechanism of action and the structure-activity relationships of this series of DNA intercalators, new dimers with additional methylene groups between the two piperidine rings have been synthesized. Addition of one methylene group in the chain preserved the activity, whereas addition of two methylene groups reduced the cytotoxicity, which finally disappeared when three methylene groups were inserted. Therefore, the study of the interaction of dimers bearing no (202), two (222) and three (232) methylene groups with the self-complementary hexanucleotide d(CGATCG)2 have been investigated by 1H and 31P nuclear magnetic resonance studies. The results reported here indicate that all dimers bis intercalate into the minihelix. The intermolecular nuclear Overhauser effects (NOEs) between the dimers and the nucleotide lead to the conclusion that the three dimers intercalate with their rigid bis-ethyl bipiperidine chain fitting the major groove of the helix. Inter-residue nuclear Overhauser effects at the DNA level, as well as induced shifts, are discussed in relation to the conformational changes induced in DNA upon intercalation and to the different activity of the dimers. PMID- 2585516 TI - Substrate binding and catalysis by glutathione reductase as derived from refined enzyme: substrate crystal structures at 2 A resolution. AB - The X-ray structure analyses of four glutathione reductase complexes and derivatives have been extended to 2 A resolution and refined. The results are discussed in conjunction with the structure of the oxidized native enzyme known at 1.54 A resolution. While the residual co-ordinate errors are around 0.2 A, some significant shifts even in this range could be established. Points of particular interest are the 3.2 A approach of C4N of nicotinamide to N5F of flavin in hydride transfer geometry, the hydrogen bond geometries of the 2' phosphate of NADPH as compared to inferior geometries for an inorganic phosphate binding together with NADH, the differential mobilities of parts of the substrates as derived from refined atomic temperature factors, and the stabilization of the thiolate of the proximal Cys63 by conformational changes of neighboring residues as well as by flavin. In addition, catalytically competent His467' is seen to interact more optimally with the sulfur of glutathione-I than with the distal sulfur of Cys58. The observed participation of water molecules for both NADPH and glutathione binding is so extensive that a prediction of the binding mode merely from the polypeptide structure would be very difficult. The accurately known geometries allowed us to draw some conclusions on the enzyme mechanism and suggest a possible scenario of the catalysis. PMID- 2585518 TI - Crystallographic data for soybean hydrophobic protein. AB - The soybean hydrophobic protein belongs to a family of proteins that contains a number of storage and phospholipid binding proteins. Its function is not known, but its overall hydrophobic nature is typical of many membrane proteins of similar size. The molecular weight is 8.3 x 10(3), and it crystallizes in the space group P2(1)2(1)2(1), with a = 52.01 A, b = 43.50 A and c = 28.80 A. The crystals diffract to 1.8 A resolution, and are thus suitable for X-ray structural studies. PMID- 2585519 TI - Segmental electrical uncoupling and conduction blocks after calcium removal and replacement in a mammalian auricle. AB - The cell-to-cell electrical conduction has been investigated in control conditions, during calcium depletion and after calcium repletion. When rat auricular strips are bathed in a Ca2+-free, EGTA-containing (5 mM) solution, the resting membrane potential slowly decreases to about -35 mV within 20 min. The electrotonic spread of intracellular current pulses remains similar to that observed in control conditions, with length constants of about 215 microns in the fibre direction and 52 microns perpendicular to it. Restoration of calcium ions to the bathing fluid at 37 degrees C induces an irreversible loss of the all-or none electrical conduction of the action potential, and the auricular fibres become split up into aggregates of electrically coupled cells delimited by border zones where the electrical coupling and the conduction of action potentials are interrupted. Inside each of those islets the resting membrane potential is uniform, but it may vary abruptly (between about -10 and -80 mV) across the border of two islets. Islets with sufficient levels of membrane potential (less than -60 mV) can generate action potentials that do not propagate to adjacent islets. This fragmentation of the cardiac tissue into electrically independent subunits explains the irreversible loss of the propagated electro-mechanical activity (calcium paradox) that is observed after calcium repletion. PMID- 2585520 TI - Alpha-myosin heavy chain cDNA structure and gene expression in adult, fetal, and premature baboon myocardium. AB - To examine cardiac myosin gene structure and expression in a non-human primate model for human heart development and disease, we have constructed a cDNA library from baboon atrium and used baboon beta-myosin heavy chain (beta-MHC)* cDNA probes to isolate atrial MHC clones. The nucleotide sequence of one such clone, lambda BMHC alpha 3, contains sequences that encode part of the light meromyosin region (LMM) and the 3' untranslated region of the baboon alpha-MHC. To study cardiac MHC gene transcription, we constructed probes from the baboon alpha-MHC cDNA for S1 nuclease analyses of RNA from atria and ventricles. To examine translational regulation of cardiac MHC gene expression, we used monoclonal antibodies (MAb) against specific alpha- and beta-MHC epitopes for Western blot analyses. In atria and ventricles from adult baboons, we detected predominantly alpha- and beta-MHC gene transcripts, respectively. In ventricles from fetal baboons at two stages of development (140 and 160 days gestation), we also detected predominantly beta-MHC gene transcripts and isoforms. To investigate changes induced by parturition, we obtained ventricles from baboons that were prematurely delivered at 140 days gestation and supported for 10 days in an extrauterine environment. In contrast to adult and fetal patterns, we observed an increase in alpha-MHC transcripts and isoforms in ventricles of premature baboons. Because alpha-MHC gene expression is increased in premature baboons (total age of 150 days) compared to their older 160 day fetal counterparts, the induction of ventricular alpha-MHC synthesis must have resulted from factor(s) associated with parturition or prolonged mechanical ventilation rather than at predetermined stages of gestational development. PMID- 2585521 TI - Acetylcholinesterase molecular forms in muscle and non-muscle cells of rat heart. AB - Experiments were performed to determine the cellular associations of the molecular forms of acetylcholinesterase (AChE) in adult rat heart. For this purpose, a cardiac muscle and a non-muscle fraction were isolated from rat heart ventricles after perfusion with collagenase and hyaluronidase, extracts of these fractions were subjected to ultracentrifugation on linear density gradients of sucrose (5-20%), and fractions of these gradients were analyzed for AChE activity. The results show that only globular AChE molecular forms were present in isolated cardiac muscle cells. Globular AChE forms were also present in the non-muscle cells fraction but in different proportions. The proportions of globular AChE forms plus the high specific activity of choline acetyltransferase in the non-muscle cell fraction suggest that this fraction contains cholinergic nerve fragments. The results of this study also show that asymmetric AChE is released during the perfusion of heart with the digestive enzymes, which suggests that asymmetric AChE is bound to the extracellular matrix of heart. PMID- 2585522 TI - Enzyme release from chick myocytes during hypoxia and reoxygenation: dependence on pH. AB - On reoxygenation of ischemic or hypoxic hearts a sudden release of cytosolic enzymes coupled with hypercontraction and cell injury occurs, which has been termed the "oxygen paradox". We have attempted to imitate this phenomenon in cultured chick myocytes to try to find the cause of this sudden enzyme release. During 4 hours of normoxic perfusion (pH 7.4) monolayer cultures of chick embryonic myocytes retain their normal morphology, beat rhythmically, and show no release of creatine kinase (CK) into the perfusate. Hypoxic perfusion (O2 less than or equal to 0.25 microliter/ml) stops cell contraction (15-20 min) and causes "blebbing" of the sarcolemma (20-30 min). Membrane blebs increase in size and number with continuing hypoxia and eventually the cells become irreversibly damaged. Perfusion at pH 7.4 leads to a release of CK shortly after membrane damage occurs (30-40 min), with peak enzyme levels at 60-90 min. Reoxygenation after 120 min hypoxia does not exacerbate release. Hypoxic perfusion at pH 7.0 suppresses the release of CK from the cells despite extensive membrane blebbing. Normoxic perfusion at pH 7.4 after 100 min hypoxia (pH 7.0) causes an efflux of enzyme from the irreversibly injured cells. This can be prevented by reoxygenating the cells at pH 7.0 and stimulated by raising the pH of the hypoxic perfusate to 7.4. Shorter hypoxic periods (30 mins) at pH 7.0 followed by normoxic perfusion at pH 7.4 lead to a sudden large efflux of CK, arrhythmic contractions and hypercontraction of myofilaments, i.e. the typical symptoms of the "oxygen paradox". Thus changes in external pH can influence the release of intracellular enzymes during hypoxia and reoxygenation. PMID- 2585524 TI - Chronobiology: timing may optimize treatments. PMID- 2585523 TI - Loss of heterozygosity in breast cancer: cause or effect? PMID- 2585525 TI - Stanford scientists ride out earthquake. PMID- 2585526 TI - Impact of sequester of funds on NCI's 1990 budget. PMID- 2585527 TI - Model state uses cigarette tax to fund cancer research. PMID- 2585529 TI - Induction of antitumor immunity in mice by allo-major histocompatibility complex class I gene transfectant with strong antigen expression. AB - An allo-major histocompatibility complex class I gene (H-2Kb) was transfected to murine mastocytoma P1.HTR (P815 subline) cells, after which several transfectant clones were obtained. Two clones, which expressed a low level of H-2Kb antigen, grew well and killed the syngeneic DBA/2 mice when they were inoculated ip. These mice lived longer than the mice given injections of the parental P1.HTR tumor. However, one clone, which expressed a high level of H-2Kb antigen, was rejected completely by the syngeneic DBA/2 mice and induced a generation of H-2Kb-specific cytotoxic T cells. Interestingly, the mice that had rejected the clone with high H-2Kb expression received strong anti-tumor immunity for rejection of the parental P1.HTR tumor challenged at the high dose. PMID- 2585528 TI - Health practices and cancer mortality among active California Mormons. AB - Religiously active Mormons in California are a nonsmoking population with unusually low risk for cancer. This finding is based on the results of our 1979 questionnaire survey of life-style and the 8-year (1980-1987) follow-up of mortality among 5,231 Mormon high priests and 4,613 wives 25-99 years of age. Our study, which is the first prospective cohort study of Mormons, shows low standardized mortality ratios (SMRs) for this population, relative to those for whites in the general population in the United States, which are defined as 100. The SMRs for males are 47 for all cancers, 52 for cardiovascular diseases, and 47 for all causes; the SMRs for females are 72 for all cancers, 64 for cardiovascular diseases, and 66 for all causes. For middle-aged high priests adhering to three health practices (never smoking cigarettes, engaging in regular physical activity, and getting proper sleep), the SMRs are 34 for all cancers, 14 for cardiovascular diseases, and 22 for all causes. These results have been largely replicated in an active Mormon-like subgroup (white nonsmokers attending church weekly) from a representative sample of residents of Alameda County, CA. Our findings confirm and expand on previous descriptive studies of Mormons and demonstrate how these results can be generalized. PMID- 2585531 TI - Flutamide-induced diarrhea secondary to lactose intolerance. PMID- 2585530 TI - Differences in incidence rates of cancers of the respiratory tract by anatomic subsite and histologic type: an etiologic implication. AB - Data from nine population-based cancer registries participating in the Surveillance, Epidemiology, and End Results Program (1973-1982) were analyzed to determine whether the incidence of different histologic types of respiratory tract cancers varies by anatomic location. The variation in cancer incidence among respiratory tract subsites was remarkable for squamous cell carcinoma, but the variation was less prominent for adenocarcinoma. The rates of squamous cell carcinoma and adenocarcinoma along the airways correspond closely with the deposition pattern of large and small smoke particles, respectively. Also, the rates of adenocarcinoma parallel the distribution of surface glandular cells of the respiratory tract. Our results support the hypothesis that anatomy and physiology, in conjunction with size of particles in inhaled cigarette smoke, play an important role in the genesis of specific histologic types of respiratory tract cancers. PMID- 2585533 TI - Mycosis fungoides and occupation in Sweden. PMID- 2585532 TI - Phase I trial of semustine plus weekly fluorouracil and high-dose leucovorin calcium in patients with advanced colorectal cancer. PMID- 2585534 TI - Acute pulmonary response in healthy, nonsmoking adults to inhalation of formaldehyde and carbon. AB - Formaldehyde (HCHO) is a common chemical found in occupational and residential environments and has been suggested as a cause of asthmalike symptoms in some individuals. Clinical and animal studies suggest that HCHO adsorbed on respirable particles may elicit a greater pulmonary physiologic and inflammatory effect than gaseous HCHO alone. The purpose of this study was to determine if respirable carbon particles have a synergistic effect on the acute symptomatic and pulmonary physiologic response to HCHO inhalation. We randomly exposed 24 normal, nonsmoking, methacholine-nonreactive subjects to 2 h each of clean air, 3 ppm formaldehyde, 0.5 mg/m3 respirable activated carbon aerosol, and the combination of 3 ppm formaldehyde plus activated carbon aerosol. The subjects engaged in intermittent heavy bicycle exercise (VE = 57 l/min) for 15 min each half hour. Measures of response included symptom questionnaires, spirometry, body plethysmography, and postexposure serial peak flows. Formaldehyde exposure was associated with significant increases in reported eye irritation, nasal irritation, throat irritation, headache, chest discomfort, and odor. We observed synergistic increases in cough, but not in other irritant respiratory tract symptoms, with inhalation of formaldehyde and carbon. Small (less than 5%) synergistic decreases in FVC and FEV3 were also seen. We observed no HCHO effect on FEV1; however, we did observe small (less than 10%) significant decreases in FEF25-75% and SGaw which may be indicative of increased airway tone. Overall, our results demonstrated synergism, but the effect is small and its clinical significance is uncertain. PMID- 2585535 TI - Genotoxicity evaluation in patients on phenobarbital monotherapy by sister chromatid exchange. AB - The potential of phenobarbital to interact with DNA has been studied using the sister chromatid exchange (SCE) assay in peripheral lymphocytes of nine adult male patients with epilepsy and of their matched controls. All patients were otherwise healthy individuals, treated chronically with phenobarbital in monotherapy. No statistically significant differences in SCE levels were found between the patient and control groups. Smoking was associated with increased SCE frequencies. The experiment was repeated with five available patients, using a slightly modified methodology. Although different SCE scores were obtained, the results of both tests were comparable. PMID- 2585536 TI - Diminished thymosin alpha-1 levels in persons exposed to 2,3,7,8 tetrachlorodibenzo-p-dioxin. AB - There is evidence from animal studies that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) impairs immune responses, with the thymus being a principal target organ. The purpose of this study was to evaluate thymic function, through measurement of thymic hormone levels, in persons exposed to TCDD. We examined thymosin alpha-1 (Thya-1) levels in sera from a group of 94 persons who were presumed to be exposed to TCDD from living, working, or recreating in a contaminated residential area. We compared these results, along with results from in vitro and in vivo tests of immune function, with those from a group of 105 unexposed persons who were similar with regard to age, sex, and race. The exposed group had a significantly lower mean Thya-1 serum level (977.3 +/- 304.1 pg/ml vs. 1148.7 +/- 482.1 pg/ml, p less than .01 by t-test). We also found a statistically significant trend of decreasing Thya-1 levels with increasing number of years of residence in the TCDD-contaminated area. However, Thya-1 levels were not associated with other measures of immune function in the TCDD-exposed group. Thus, while the principal findings suggest that long-term TCDD exposure may be associated with diminished secretion of Thya-1, the lack of an association with an increased prevalence of clinically diagnosed immune suppression in these TCDD exposed persons makes the biologic significance of the findings unclear. Further studies are needed to more fully evaluate possible long-term TCDD-induced effects on the thymus and human immune function. PMID- 2585537 TI - Effects of gestational exposure to Tordon 202c on fetal growth and development in CD-1 mice. AB - The teratogenic effects of Tordon 202c, a picloram and 2,4-D combination formulation, are unknown. Pregnant CD-1 mice were exposed to Tordon 202c in the drinking water at concentrations of 0.10, 0.21, and 0.42% from d 6 to 15 of gestation. Fetal growth parameters, including body weight and crown-rump length, were reduced in a dose-dependent manner, as was placental weight. The incidence of dead fetuses/resorptions and malformed fetuses (especially cleft palate) was increased in the highest dosage group. A subtle indication of maternal toxicity was noted in the highest dosage group as evidenced by decreased water consumption and increased relative liver weight. The present study suggests that Tordon 202c is embryotoxic and teratogenic in CD-1 mice when administered during organogenesis. PMID- 2585538 TI - Comparative inhalation toxicity of technical chlordane in rats and monkeys. AB - Technical chlordane (1,2,4,5,6,7,8,8-octachloro-3a,4,7,7-tetrahydro-4,7 methanoinda ne) is used extensively for control of certain wood-boring insects. The present study was conducted to evaluate the inhalation toxicity of technical chlordane in rats and monkeys. Range-finding (28-d) and subchronic (90-d) inhalation studies with Wistar rats, and subchronic (90-d) inhalation studies with cynomolgus monkeys were conducted. In the range-finding study in rats, the threshold of toxicity for technical chlordane was approximately 5.8 micrograms/l. Among the observations made during the course of the 90-d study, in which technical chlordane was administered by inhalation to rats and monkeys at concentrations close to 0.1, 1.0, and 10 micrograms/l, the most significant were associated with alterations in the liver and were confined to rats only. However, in the rat, the effects on the liver were largely reversible during 90 d following cessation of administration of technical chlordane. The no-effect level of chlordane inhalation in rats appears to be between 0.1 and 1.0 microgram/l, while in monkeys the no-effect level is in excess of 10 micrograms/l. This study demonstrated that the monkey, a species closely related to humans, can tolerate relatively high chlordane concentrations without any adverse effects. PMID- 2585539 TI - Exposure to 1 ppm ozone attenuates the immediate antigenic response of canine peripheral airways. AB - The effect of oxidant exposure on the immediate airway response to immunologic challenge is controversial. We investigated the response of canine peripheral airways to antigen aerosol, 1-3 h and 24 h after a 5-min exposure to 1 ppm ozone. In dogs that were natively sensitive to Ascaris suum antigen, resistance to flow through the collateral system (Rcs) was measured using the wedged bronchoscope technique. In eight dogs, four sublobar segments of each lung were wedged: two were exposed to ozone for 5 min and two (control) received air with 5% CO2. Ozone caused a mean ( +/- SE) increase in Rcs of 75 +/- 15%, which returned to baseline after 1-3 h. The increase in Rcs elicited by subsequent administration of antigen aerosol (25 microliters, 0.27 mg protein/ml) to the ozone-exposed segments (312.0 +/- 70.6%) was attenuated by 22% compared to controls (398.9 +/- 83.0%; p less than .05). In another series of experiments (n = 5), segments were exposed to ozone or air and challenged with antigen 24 h later and a significant attenuation (38%) of the antigen-induced increase in Rcs was detected compared to controls (178.5 +/- 57.9 vs 289.0 +/- 62.2; p less than .05). Cellular influx of polymorphonuclear leukocytes (PMNs) was not detected by bronchoalveolar lavage (BAL) 1-3 h after ozone, but was found after 24 h (19.8 vs. 4.7%; p less than .01). A significant increase in PMNs was detected in exposed subepithelial tissues 1-3 h after ozone compared to unexposed tissues. Tissue PMNs were not significantly different from unexposed tissues after 24 h, but a shift toward degranulation of mast cells was detected in ozone-exposed tissues at this time. These data suggest that the Rcs response to antigen is attenuated 1-3 h and 24 h after acute (5 min) exposure to 1 ppm ozone, and this effect occurs independently of PMNs in the airways. PMID- 2585540 TI - Preexposure to ozone blocks the antigen-induced late asthmatic response of the canine peripheral airways. AB - The influence of exposure of the airways to ozone on acute allergic responsiveness has been investigated in several species. Little is known, however, about the effect of this environmental pollutant on the late asthmatic response (LAR) in animals in which it is exhibited. The purpose of this study was to evaluate this effect in the canine peripheral airways and to assess the potential role of mast cells in modulating the effect. A series of experiments on seven mongrel dogs demonstrated that the numbers of mast cells at the base of the epithelial region of small subsegmental airways exposed to 1 ppm ozone for 5 min were significantly (p less than .01) increased 3 h following exposure compared to air exposed or nonexposed control airways. In a second series of experiments performed on eight additional mongrel dogs with inherent sensitivity to Ascaris suum antigen, antigen aerosol was administered to the sublobar segment 3 h following ozone preexposure when mast cell numbers were presumed to be increased. These experiments were performed to determine whether ozone preexposure could enhance the late-phase response to antigen by virtue of acutely increasing the number of mast cells available to bind the antigen. Four of the eight dogs tested displayed a late-phase response to antigen following air-sham preexposure. In these four dogs, simultaneous ozone preexposure of a contralateral lobe completely blocked the late-phase response to antigen. These results indicate that the consequences of a single exposure to ozone persist beyond its effects on acute antigen-induced bronchoconstriction and extend to the complex processes involved with the late response. This attenuating effect of ozone is seen under conditions where mast-cell numbers in the airways are increased above baseline levels. PMID- 2585541 TI - Hypertension and associated cardiovascular abnormalities induced by chronic barium feeding. AB - Because high barium concentrations (2-10 ppm) in human drinking water have been reported to be associated with elevated cardiovascular mortality, hypertension and other cardiovascular effects were sought in rats chronically exposed for 1-16 mo to drinking water containing 1, 10, or 100 ppm barium. From weaning, female Long-Evans rats were kept in a "low contamination" environment and fed a diet low in trace metals. Their drinking water was deionized, fortified with 5 essential trace metals, and either 0, 1, 10, or 100 ppm barium was added. Indirect systolic pressure of unanesthetized rats was measured in triplicate at 1, 2, 4, 8, 12, and 16 mo. Average systolic pressure increased significantly after exposure to 100 ppm barium for 1 mo or longer and after exposure to 10 ppm barium for 8 mo or longer. After 4 or 16 mo, barium exposure failed to alter organ weights or tissue concentrations of calcium, magnesium, sodium, or potassium; however, both 10 and 100 ppm barium resulted in significant increases in tissue barium. Rats exposed to 100 ppm Ba for 16 mo exhibited depressed rates of cardiac contraction and depressed electrical excitability in the heart. Hearts from these maximally exposed rats also had significantly lower ATP content and phosphorylation potential, as measured by 31P NMR spectroscopy. Although the barium-induced increase in the blood pressure of rats was modest, comparable mild hypertension in humans would have major health implications. PMID- 2585542 TI - Secretion of nerve growth factor in cultures of glial cells and neurons derived from different regions of the mouse brain. AB - The regional ability of central neurons and glial cells to produce nerve growth factor (NGF) was studied in vitro. NGF secretion was compared in cultures of perinatal astrocytes or embryonic neurons that were derived from various mouse brain structures. No regional differences were detected among cultures of post natal day 2 glial cells of hippocampal, cortical, striatal, or mesencephalic origin. In all cases, levels of NGF released by the cells were very similar. They were closely correlated to the growth rate as shown by the fact that exponentially growing cells produced relatively more factor than did confluent cells, a finding in agreement with previous observations. Unlike growth-phase cells, primary astrocytes immediately plated at high cell density did not secrete any assayable factor before the 7th day of culture. Levels of NGF found during the following days remained low. In contrast, striking differences were observed among cultures of embryonic neurons. NGF was found in relatively large amounts in cultures of embryonic day 17 or 19 striatal neurons, whereas media conditioned by neurons from the mesencephalon, cortex, or septum contained much less factor. Amounts of NGF assayed in cultures of hippocampal neurons varied with the time of sampling of this brain structure. Levels of factor were significantly higher in media conditioned by embryonic day 19 neurons than in media of embryonic day 17 neurons. However, amounts of NGF found in supernatants of hippocampal neurons remained smaller than those present in cultures of striatal nerve cells. Altogether, the results suggest that, in addition to astrocytes, central neurons may also synthesize and secrete NGF in vitro and that this phenomenum is dependent on both the origin and the developmental stage of the neuronal population. PMID- 2585543 TI - Rapid growth of regenerating axons across the segments of sciatic nerve devoid of Schwann cells. AB - The characteristic response of Schwann cells (SC) accompanies peripheral nerve injury and regeneration. To elucidate their role, the question of whether or not regenerating axons can elongate across the segments of a peripheral nerve devoid of SC was investigated. Rat sciatic nerve was crushed so that the continuity of SC basal laminae was not interrupted. A segment about 15 mm long distal to the crush was either repeatedly frozen/thawed to eliminate SC or scalded by moist heat which, in addition, denatured the proteins in the SC basal laminae, too. Both sensory and motor axons grew rapidly across the frozen/thawed segment of the nerve. Their rate of elongation was reduced by only 30% in comparison to control crushed nerves. SC were not present along the path of growing axons adhering tightly to the bare SC basal laminae. The rate of elongation of regenerating sensory and motor axons in scalded nerve segments was eight times lower than in control crushed nerves. SC were present in that part of the scalded region that had been invaded by the regenerating axons but no further distally. These results suggest that acellular basal laminae of SC provide very good, although not optimal, conditions for elongation of regenerating sensory and motor axons. If biochemical integrity of the basal lamina is destroyed, the regenerating axons must be accompanied or preceded by viable SC. and axon elongation rate is significantly reduced. PMID- 2585544 TI - Magnocellular neurosecretory axon regeneration into rat intrahypothalamic optic nerve allografts. AB - To test the working hypothesis that neurosecretory neuronal regeneration is largely dependent on microenvironmental conditions at the lesion site, intact or predegenerated optic nerves were allografted intrahypothalamically into the hypothalamo-neurohypophysial tract. Neurosecretory axons regenerated consistently into all grafts. Early regeneration proceeded without glial cell association. At later stages of regeneration, however, neurosecretory axons were associated consistently with astrocytes that, within perivascular spaces, were surrounded by a basal lamina. Axons in contact with that basal lamina had the characteristics of terminals, suggesting functional recovery. It is postulated that it is the initial absence of a blood-brain barrier at the graft site that provides a microenvironment similar to that in the neural lobe and that induces neurosecretory axon regeneration. PMID- 2585545 TI - Phosphatidylinositol-specific phospholipase C solubilized G2 acetylcholinesterase from plasma membranes of chromaffin cells. AB - Using whole homogenates and defined subcellular fractions of bovine adrenal medulla, we investigated the properties of the dimeric G2 molecular form of acetylcholinesterase (AChE), its distribution, and the mode of attachment to chromaffin cells. Our studies indicate that a substantial fraction of the G2 form is specifically susceptible to solubilization by phosphatidylinositol-specific phospholipase C (PIPLC) from subcellular fractions enriched with plasma membrane fragments. The results suggest that the G2 form of AChE is anchored in the plasma membrane to a glycolipid domain that contains phosphatidylinositol. Since a Ca+2 dependent PIPLC has been previously described in chromaffin granules, it is possible that the adrenal AChE could be released by a system reminiscent of that involved in the case of the surface glycoprotein of Trypanosoma brucei. PMID- 2585546 TI - Release from live choroid plexus of apical fragments and electrophoretic characterization of their synthetic products. AB - Protein synthesis and secretion by the choroid plexus (CP) has been implicated as a major source of certain proteins in cerebrospinal fluid (CSF), such as transthyretin. The suggestion that proteins are elaborated from CP through apocrine secretion has been borne out by the presence of newly labeled proteins in apical protrusions from CP (Agnew et al.: Cell and Tissue Research 208:261 281, 1980a). When the protrusions (aposomes) separate from the cells, they continue to incorporate labeled amino acids (Gudeman et al.: Tissue and Cell 19:101-109, 1987). In the present work the formation of aposomes in live CP explants indicated that these spheroids were not the result of fixation. Aposomes were also identified within rat CSF by immunohistochemistry with monoclonal directed against aposomes as well as with anti-transthyretin serum. The protein product of aposomes was characterized by 2-dimensional SDS-PAGE and compared to the protein products of whole CP tissue. Paradoxically, transthyretin, a heavily labeled protein in the tissue, was virtually undetected in the aposome synthetic profile. However, four other proteins were expressed in relatively equivalent amounts by the aposomes. The presence of mRNA in aposomes was detected with a poly dT probe, and the presence of actin was revealed by phalloidin staining of aposomes. These studies provide a more comprehensive definition of aposomes, but the functions of their secreted proteins remains to be determined. PMID- 2585547 TI - X-ray diffraction analysis of myelin lipid/proteolipid protein multilayers. AB - To examine the proposal that myelin proteolipid protein underlies the adhesion of neighboring membranes in central nervous system (CNS) myelin, we carried out X ray diffraction studies on the structure and interactions of model bilayers composed of total myelin lipids plus proteolipid apoprotein (PLP). Total myelin lipids were used because their heterogeneity was expected to provide an appropriate environment for the integral membrane protein to achieve its native conformation and establish appropriate contacts with the apposed bilayer. We found that incorporation of PLP into myelin lipid bilayers, whether organized into multilamellar vesicles or oriented multilayers, did not appreciably affect the lamellar period, which ranged from 65-71 A. In oriented multilayers, the wide angle spacing at approximately 4.8 A, which arises from the lateral packing of lipid chains and is perpendicular to the lamellar diffraction, was less oriented and weaker in bilayers containing the protein. These results indicate that PLP was incorporated into the bilayers and had a disordering effect on the hydrocarbon chains but did not extend into the spaces between bilayers. Bilayer profiles calculated from the lamellar diffraction to about 15 A spacing did not show any major changes in the distribution of electron density, suggesting that to moderate resolution, the protein was distributed uniformly across the width of the lipid bilayer. Periodicities measured from osmotically stressed multilamellar vesicles did not depend on the presence of PLP, indicating that the protein did not form stabilizing contacts between bilayers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585548 TI - Phospholipid-derived choline intermediates and acetylcholine synthesis in mouse brain synaptosomes. AB - Endogenous free choline levels and acetylcholine (ACh) synthesis in nerve terminals were investigated using cerebral cortical synaptosomes of C57BL/6 mice. Endogenous choline was produced at a rate ten-fold faster than ACh to provide levels adequate for the formation of the latter. The combined pool size of the water-soluble intermediates derived from phosphatidylcholine (PhC), such as glycerophosphorylcholine (GpCh) and phosphorylcholine (PCh), increased significantly during the first 10-15 min of incubation and was always higher than that of free choline. These results most likely indicate an effective degradation of PhC by the combined action of phospholipase A2/lysophospholipase, as well as by phospholipase C in synaptosomes. ACh synthesis proceeded at a constant rate in the presence or absence of exogenous free choline (0-10 microM) and was almost entirely abolished in the presence of 10(-6) M hemicholinium-3. These results suggest that ACh is effectively synthesized by free choline generated in synaptosomes by a coupling mechanism involving the high-affinity choline uptake system. No changes in the production rates of choline and ACh were observed between adult and aged mice. PMID- 2585549 TI - Expression of vimentin by cultured astroglia and oligodendroglia. AB - The objective of this study was to determine whether vimentin expression by process-bearing astroglia and oligodendroglia cultured from neonatal rat cerebral cortex resembled that in brain where vimentin is common in immature astroglia and a few subpopulations of mature astroglia, but is absent in oligodendroglia. Vimentin expression was detected by immunofluorescence microscopy using a monoclonal antibody (V9) against porcine lens vimentin in combination with either antiserum against the astroglial marker, glial fibrillary acidic protein (GFAP), or with antiserum against the oligodendroglial marker, galactocerebroside (GC). Specificity of the antivimentin antibody was indicated on immunoblots of process bearing cell proteins separated by two-dimensional polyacrylamide gel electrophoresis. Enrichment of cultures for either GFAP+ astroglia or GC+ oligodendroglia was achieved by supplementation of the culture medium with fetal calf serum at 10% or 0.5%, respectively. Process-bearing cells maintained in 10% serum exhibited heterogeneity in their expression of GFAP and vimentin. Approximately half of the cells were GFAP+/vimentin+ throughout the 2-week culture period examined. GFAP+/vimentin- cells were a minor population at early times (3-4 days) in culture, but accounted for 40% of process-bearing cells after 2 weeks. Cultures maintained in reduced (0.5%) serum and stained for GC and vimentin also exhibited heterogeneity. Both GC+/vimentin+ and GC+/vimentin- cells were observed, with vimentin+ cells composing two-thirds and one-half of the GC+ population after 3 and 6 days, respectively, in reduced serum. The high incidence of vimentin expression by process-bearing astroglia and oligodendroglia suggests that these cultures contain glia in a relatively early stage of development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585550 TI - Adenosine metabolism in neurons and astrocytes in primary cultures. AB - Metabolic fate of [8-14C]adenosine was studied in primary cultures of either astrocytes or neurons from the mouse brain. In astrocytes the main metabolic route was the formation of nucleotides. Thus, synthesis of adenosine triphosphate (ATP) amounted to about 0.2 nmol X min-1 X mg-1 protein. The deamination occurred less rapidly. The total rate of formation of inosine was difficult to establish because a considerable amount of labeled inosine accumulated in the medium. The initial incorporation of radioactivity into inosine in the medium was extremely rapid, probably because of the action of an ectoenzyme. However, the labeling of inosine in the medium also continued to increase slowly throughout the incubation, maybe as a result of release of intracellularly formed inosine. The total inosine formation rate during the incubation amounted to at most 0.1 nmol X min-1 X mg-1. Hypoxanthine was formed at a corresponding rate but was released to a lesser extent. In neurons much less label was incorporated into ATP. The major metabolite was inosine, formed intracellularly at a rate of 0.2 nmol X min-1 X mg 1. In addition, there was an immediate rapid labeling of inosine (and to a lesser extent hypoxanthine) in the medium, again suggesting the action of an ectoenzyme. Neither neurons nor astrocytes released a measurable amount of nucleotides to the medium. The cellular differences in adenosine metabolism are probably of relevance for the interpretation of adenosine metabolism in brain in situ. The ectoenzyme may be of importance for rapid termination of the neuromodulator activity of adenosine, and the rapid nucleotide formation in astrocytes is in agreement with a high metabolic activity of these cells. PMID- 2585551 TI - Effect of huperzine A, a new cholinesterase inhibitor, on the central cholinergic system of the rat. AB - The present study represents the first comprehensive investigation of the effect of huperzine A (HUP-A), a new cholinesterase inhibitor (ChEI) isolated from a Lycopodium species, upon acetylcholinesterase (AChE) activity, acetylcholine (ACh) levels and release, and cholinergic receptors in rat brain following acute i.m. or i.p. administration. The study shows that HUP-A can produce a long-term inhibition of AChE activity in brain (up to 360 min) and an increase in the ACh levels up to 40% at 60 min. There is considerable regional variation in the degree of ACh elevation after HUP-A with maximal values seen in frontal (125%) and parietal (105%) cortex and smaller increases (22-65%) in other brain regions. HUP-A at concentrations of 10(-6) to 10(-4) M does not significantly alter the electrically evoked release of 3H-ACh from cortical slices. With the exception of the highest concentrations (6 X 10(-4) M) the displacement effect of HUP-A for cholinergic ligands is stronger for 3H-(-)nicotine than for 3H-QNB. A parallel autoradiographic study in the mouse shows that 60 min after i.v. injection (183 micrograms/kg) the drug is present in all brain regions, but it is particularly concentrated in certain areas such as frontoparietal cortex, nucleus accumbens, hippocampal, and striatal cortex. Radio-activity is practically absent in the whole body at 12 hr. Our study suggests that this new ChEI has interesting cholinomimetic properties, and its effects satisfy more closely established criteria for an ideal ChEI for therapeutic use than previously tested compounds. PMID- 2585553 TI - Survival of purified embryonic chick retinal ganglion cells in the presence of neurotrophic factors. AB - In a search for neurotrophic factors (NTFs) regulating retinal ganglion cell (RGC) death in the chick embryo we have used purified and cultured RGCs. Purification of RGCs from embryonic day 10 was achieved by employing the "panning" method (Silverstein and Chun: Soc Neurosci Abstr 13:1054, 1987). The obtained neuron population consisted of 97% RGCs as demonstrated by retrograde labeling with a fluorescence dye. RGCs were cultured at low density in a chemically defined medium and short-term survival (24 hr) was determined. In the absence of NTFs, less than 3% of the RGCs survived. In the presence of various crude or purified NTFs (eye, brain, and tectum extracts; glial-conditioned medium; ciliary neurotrophic factor [CNTF]; nerve growth factor [NGF]) 31% to 52% of the RGCs were maintained. The effects of NGF and CNTF were not additive. Neither acidic nor basic fibroblast growth factor was able to maintain RGCs in culture. Our results, obtained with a culture system which allowed the analysis of direct trophic actions, suggest that NGF and CNTF may be NTFs for overlapping subpopulations of chick RGCs. PMID- 2585552 TI - Autoradiographic localization of [3H]dextromethorphan in guinea pig brain: allosteric enhancement by ropizine. AB - Dextromethorphan (DM) is an antitussive with anticonvulsant activity that binds to high- and low-affinity sites in guinea pig brain homogenates. We examined the autoradiographic localization of [3H]DM using the anticonvulsant ropizine, an allosteric modifier that decreases the dissociation rate of [3H]DM. Competition studies demonstrated that the binding to brain sections was identical to that of brain homogenates [Craviso and Musacchio: Mol Pharmacol 23:629-640, 1983b]. Computer-assisted quantitative analysis of the autoradiographic images demonstrated that [3H]DM binds to discrete structures throughout the brain, but with higher density in the midbrain, pons, and medulla oblongata. The most intense labeling was observed in the rhabdoid, dorsal raphe, median raphe, caudal linear raphe nuclei, and cranial motor nerve nuclei. The central gray showed moderate to high-density labeling throughout its entire rostro-caudal extent, with very high binding in the dorsal tegmental nucleus and the locus coeruleus. Moderate and high binding was also seen in several hypothalamic structures. Distinct bands of moderate binding were seen in the pyramidal cell layer of the piriform cortex, the retrosplenial cortex, the granular cell layer of the dentate gyrus, the pyramidal cell layer of the hippocampus, and the Purkinje cell layer of the cerebellum. The striking similarity between the binding distribution of [3H]DM and sigma ligands, plus competition studies in brain homogenate, support the hypothesis that DM and sigma ligands share a common high-affinity binding site [Musacchio et al: Mol Pharmacol 35:1-5, 1989]. The distribution of [3H]DM binding provides possible anatomical substrates for both the antitussive and anticonvulsant actions of DM. PMID- 2585554 TI - Aminoglycoside antibiotics impair calcium entry but not viability and motility in isolated cochlear outer hair cells. AB - Cochlear outer hair cells have been well established as primary targets of the ototoxic actions of aminoglycoside antibiotics. These cells, isolated from the guinea pig cochlea and maintained in short-term culture, were used as a model for evaluating the acute effects of gentamicin on cell viability, depolarization induced transmembrane calcium flux, and depolarization-induced motile responses. On the basis of morphology and fluorochromasia, the presence of extracellular gentamicin as high as 5 mM did not affect the viability of the cells for up to 6 hr, the longest time tested. Viable cells showed binding of fluorescently tagged gentamicin to their base but excluded the drug from their cytoplasm. In response to [K+]-depolarization, intracellular calcium levels (monitored with the fluorescent calcium-sensitive dye fluo-3) increased from a resting value of 218 +/- 102 nM to 2,018 +/- 1,077 nM concomitant with a cell shortening of 0.7% +/- 1.3%. The depolarization-induced calcium increase was apparently caused by calcium entry into the cell as it was inhibited by the calcium-channel blocker methoxyverapamil and prevented in the absence of extracellular calcium. Both gentamicin and neomycin blocked the [K+]-induced calcium increase at an IC50 of 50 microM. Despite the inhibition of calcium entry the ability of the outer hair cells to shorten under [K+]-depolarization was not impaired; in fact, cell shortening was even more pronounced in the absence of calcium influx (2.6% +/- 1.4%). This argues effectively against the existence of a calcium-dependent actomyosin-mediated component in [K+]-induced shape changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585555 TI - American Association for the Surgery of Trauma, 1988 annual session. PMID- 2585556 TI - Pharmacokinetic monitoring of nephrotoxic antibiotics in surgical intensive care patients. AB - An assessment of the dosage regimens prescribed for potentially nephrotoxic antibiotics (amikacin, gentamicin, tobramycin, and vancomycin) was undertaken on surgical intensive care unit patients. In 166 patients, 224 series of blood antibiotic level determinations were obtained. Using individualized pharmacokinetic determinations, the regimens were revised as necessary to provide optimal blood levels. Because of variable volumes of distribution and elimination rates, dosing according to standard clinical guidelines produced significantly lower peaks than did pharmacokinetically determined regimens for gentamicin (p less than 0.005), tobramycin (p less than 0.0001), and vancomycin (p less than 0.05). Importantly, fewer patients achieved therapeutic levels with the original regimens than with the revised regimens for gentamicin (9% vs. 91%, p less than 0.0005), tobramycin (27% vs. 92%, p less than 0.0001), and vancomycin (30% vs. 69%, p less than 0.0001). Individualized pharmacokinetic analysis of potentially nephrotoxic antibiotics in critically ill patients is essential if therapeutic, non-toxic levels are to be maintained. PMID- 2585557 TI - Postgraduate trauma education; the surgeon; the cost. AB - Injuries account for 3.6 million hospital admissions and approximately 100 billion dollars in health care costs annually. Surgical educators have expressed concern about the adequacy of postgraduate trauma education in light of this trauma epidemic. The purpose of this report was to evaluate our residents' trauma exposure and to examine the associated cost of training a physician to treat critically injured patients. From July 1982 through June 1987, 38,714 patients were evaluated for injuries in the emergency department. Five thousand sixty-one patients required admission to the hospital, and of these, 2,045 were admitted to the intensive care unit. In addition, 3,851 major trauma operations were performed during this 5-year period. The majority of these procedures were neurosurgical and orthopedic; however, we have seen an increasing percentage of abdominal operations in the last 2 years. The last five graduating chief residents averaged 181 major trauma operations during their training. The hospital currently writes off an average of $250,000 per month in trauma patient non-collections. This averages to 1.5 million dollars per resident for 5 years of trauma education in our institution. It is imperative that we continue to train trauma surgeons to manage critically ill patients; however, society must address the enormous cost of doing so. PMID- 2585559 TI - Posterior acetabular fracture-dislocations: fragment size, joint capsule, and stability. AB - In acetabular fractures, the size of a significant posterior wall fragment remains undefined as it affects joint stability. The purpose of this study was to quantitatively evaluate fragment size and hip stability in cadaveric specimens after serial osteotomies. Also, the role of the posterior capsule, in the various osteotomies, was evaluated for changes in hip stability. We found that fragments involving 25% or less of the acetabulum are insignificant, i.e., do not affect joint stability, while fragments involving 50% or more are significant. The significance of transitional fragments (25-50% of the acetabulum) is determined by the posterior capsule. PMID- 2585558 TI - Esophageal tracheal combitube, endotracheal airway, and mask: comparison of ventilatory pressure curves. AB - The esophageal tracheal Combitube (ETC) is a new airway especially designed for airway maintenance and ventilation in unconscious patients such as those requiring CPR. The ETC may be used as an esophageal obturator or an endotracheal airway. Previous studies yielded a significantly higher mean arterial oxygen tension (PaO2) during ventilation using an ETC in the esophageal position compared to a conventional endotracheal airway (ETA). To investigate this phenomenon, endotracheal and airway opening pressures were examined in 12 patients in randomized order during ventilation with an ETC in the esophageal position, with an ETA, and with a mask, respectively. In this study again the PaO2 was higher with ETC compared to ETA. The following differences in intratracheal pressure and flow could be found for ETC when compared to ETA: smaller rising pressure during inspiration, prolonged expiratory flow time, and formation of a small positive end expiratory pressure (PEEP). These factors may be responsible for the improved oxygen tension with ETC. Comparing mask to ETC ventilation, PaO2 did not differ; however, mean arterial carbon dioxide tension was higher during mask ventilation. PMID- 2585560 TI - Stabilization of spinal injury for early transfer. AB - We have reviewed the means of transport and type of stabilization used for all patients with acute spinal cord injuries (SCI) transferred to our center since 1985 to determine what effect these variables may have had on change in level of impairment and probability of neurologic improvement after arrival. Sixty-one patients were reviewed, 47 males and 14 females, with a mean age of 34 years. Twenty-five patients (41%) were transported by ground ambulance, 33 (54%) by helicopter, three (5%) by fixed-wing aircraft. Forty-three patients (70.5%) had cervical spine injuries, 11 (18%), thoracic spine injuries, and seven (11.5%), lumbar spine injuries. Fifty-one patients (84%) were transferred within 24 hours of injury. A variety of standard methods of stabilization were used during transport. No patient suffered ascending level of injury as a result of early transfer. Level of function improved before discharge in 26 of 61 patients (43%); patients transported within 24 hours were more likely to show improvement (25/51) than those transported after 24 hours (1/10). There was no significant difference in the probability of improvement between ground (8/25) or air (18/36) transport. Skeletal traction was used before transfer in only four of 43 patients with cervical spine injuries, and was maintained as a method of long-term stabilization in two patients. We conclude that acute SCI patients can be safely transported by air or ground using standard precautions. Distance and extent of associated injury are the best determinants of mode of transport. Skeletal traction does not appear to be a prerequisite for safe, early transfer of SCI patients. PMID- 2585561 TI - The power of the Z statistic: implications for trauma research and quality assurance review. AB - The Z statistic can be used to test whether the observed number of survivors in a specific trauma population is significantly different from what would be expected based on the Major Trauma Outcome Study (MTOS) norms. However, as with any statistic, inferences based on the Z statistic should be made with care. This is particularly true when a non-significant Z statistic is observed. The purpose of this paper, using data from a large, urban trauma registry, is to illustrate how the power of the Z statistic, or its ability to detect a difference between observed and expected survival, is influenced by the magnitude of the difference, the direction of the difference, the survival probability distribution of the study population, and the sample size. The implications for trauma research and quality assurance review are discussed. PMID- 2585562 TI - A comparison of the cerebral and cardiovascular effects of complete resuscitation with isotonic and hypertonic saline, hetastarch, and whole blood following hemorrhage. AB - Hemorrhagic shock and closed head injury often accompany severe trauma. Hypertonic saline may be beneficial in these patients, but few have examined its properties when sufficient volume is infused to achieve sustained resuscitation. Solutions of 6% NaCl (HS), 0.9% NaCl (NS), 6% hetastarch (HE), and whole blood (WB) were used to resuscitate swine in hemorrhagic shock (MAP less than 30 mm Hg). The endpoint of resuscitation was normal oxygen delivery (DO2). Measurements of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and intracranial elastance (ICE) were made in the absence and presence of an epidural mass, created by inflating an epidural balloon. HS resuscitation resulted in a lower ICP [5 +/- 1 versus 9 +/- 2 (HE), 17 +/- 3 (NS), and 10 +/- 3 (WB) mm Hg; p = 0.016], and normalization of CPP throughout resuscitation. Animals resuscitated with NS had a lower CPP by the end of resuscitation [CPP = 45 +/- 4 for NS group, versus 63 +/- 4 (HE), 66 +/- 4 (HS), and 63 +/- 5 (WB) mm Hg; p = 0.009]. ICE fell markedly in the HS group, [a decrease of 12 +/- 2 vs. a rise of 5 +/- 3 (HE), 2 +/- 3 (NS), and 6 +/- 3 (WB) mm Hg/ml; p = 0.0005]. This improvement was even more dramatic in the presence of an epidural mass [a fall of 21 +/- 3 vs. no change (HE, WB) and a rise of 4 +/- 3 (NS) mm Hg/ml; p = 0.0005]. For hemorrhage accompanied by severe head injury, resuscitation with HS may benefit victims by decreasing ICP and diminishing the effects of an intracranial mass. PMID- 2585564 TI - HIV infection rates in a trauma center treating predominantly rural blunt trauma victims. AB - Human immunodeficiency virus (HIV) infection rates among 1,497 consecutive adult trauma victims triaged from rural and urban sectors to a statewide trauma center in Baltimore were studied. Those studied were 71.7% men, 77.4% whites, 63.2% vehicular trauma victims, 11.2% assault victims, and 25.7% other trauma victims. Non-Baltimoreans predominated (86.0%) and 32.7% were 25 to 39 years of age. Overall, 1.67% of the victims were HIV antibody positive. Significantly higher infection rates were seen in men (1.96% vs. 0.95%; p less than 0.02), non-whites (4.13% vs. 0.95; p less than 0.005), assault victims compared with vehicular and other trauma victims (5.99% vs. 1.06% vs. 1.30%, respectively; p less than 0.001), and Baltimore City residents (3.81% vs. 1.32%; p less than 0.03). Among those 25 to 39 years of age, 68.0% of the HIV infections were noted. Results suggest that HIV infection rates among trauma center patients are a reflection of the patient population served. PMID- 2585563 TI - Pontomedullary tears and other gross brainstem injuries after vehicular accidents. AB - In a series of 988 autopsied victims of road crashes, there were 36 (3.6%) cases of gross primary brainstem injury. These fell into three groups. The first comprised eight cases of pontomedullary tearing without other gross brain injury: in seven of these, there were associated atlanto-occipital dislocations and/or high cervical fracture-dislocations. The usual cause appeared to be facial impact inducing acute hyperextension. Second, there were 17 cases of pontomedullary tearing associated with other brainstem lacerations and/or major damage elsewhere in the brain: in all, there were fractures of the skull base, typically transverse middle fossa fractures. Most of these injuries appeared to be due to facial impacts transmitting force to the anterior skull base, although hyperextension was also a factor in some. There was a third heterogeneous group of 11 cases with brainstem lacerations in sites other than the pontomedullary junction: in some of these it appeared that the impacts had caused skull base fractures by inducing calvarial torsion. In this series, the proportion of motorcyclists (41.7%) was double the expected figure. The use of a helmet modifies the mechanisms of impact head injury; the overall benefits of helmet use are well established, but there is need for more research on helmet design. PMID- 2585565 TI - The pain of burns: characteristics and correlates. AB - This study examined the characteristics of pain experienced by burned patients. Sources of inter-individual variations were also studied and the interrelationships between anxiety, depression, and pain were investigated. Forty two adult patients hospitalized for burn injuries participated in the study. The McGill Pain Questionnaire and a visual analogue scale were employed to measure the pain experienced at rest and during therapeutic procedures. Anxiety and depression levels were assessed with the Spielberger State Anxiety Inventory, the Beck Depression Inventory, and visual analogue scales. The results showed that the pain varies greatly from patient to patient and undergoes wide fluctuations over time in each patient. The greatest pain is usually experienced during therapeutic procedures, the patients reporting significantly more pain on these occasions than at rest. Variations in pain severity were not related to socio demographic characteristics of the patients, the length of time elapsed since the injury, or the quantity of analgesics administered. The extent of the burns was a significant predictor of pain but only in the first week after the injury. High levels of anxiety or depression were not necessarily associated with higher pain scores during therapeutic procedures but the patients who were more anxious or depressed tended to report more pain when at rest. These results are discussed in relation to pain management strategies, with particular emphasis on the need for the analgesic therapy to be highly individualized and frequently adjusted. PMID- 2585567 TI - Firearms' decreased role in New Jersey homicides after a mandatory sentencing law. AB - In 1981 New Jersey adopted a law requiring a mandatory minimum prison sentence for use or possession of a firearm in a variety of crimes. New Jersey firearms homicides as a per cent of all New Jersey homicides increased from 1974 to 1980 and decreased from 1981 through 1986. No similar change was observed for homicides in the balance of the U.S. or for suicides in New Jersey or the balance of the U.S. The findings suggest an effect of the mandatory minimum sentencing law on firearms homicides. PMID- 2585566 TI - Urban trauma: an analysis of 1,116 paediatric cases. AB - Over a 2-year period 1,116 children admitted to an urban teaching hospital were studied prospectively. The overall group was analysed as to the nature of the injury and a subgroup of seriously injured children was identified and further analysed. All deaths were examined as to their cause and possible preventable as well as salvageable factors. The predictive value of the Trauma Score (T.S.) and Method of Injury (M.O.I.) were evaluated for their prospective prediction of serious injury as determined by the Injury Severity Score and outcome. Most of the children were not seriously injured, with the most common injury being due to a fall (57%) and involving a single injury to the upper limb. With the subgroup of 143 children (13% of the total) who suffered serious injuries, the cranial cavity (90%) was the most common site of injury, occurring most often in pedestrians (31% of the total injured). There were 16 deaths in the series, representing 1.4% of all paediatric trauma admissions and 11% of the admissions who were seriously injured. All deaths were related to motor vehicle accidents and associated with serious head injury. A Trauma Score less than or equal to 12 accurately included all deaths but when correlated with the I.S.S., the Trauma Score had a specificity of 99% and a positive predictive value of 86%; its sensitivity was only 27%. The Method of Injury was associated with an overtriage rate of 300% in relation to the I.S.S.. Of children admitted following pedal cycle accidents only 9% were wearing helmets. Of car occupants injured, 39% were unrestrained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585569 TI - Fractures of the posterior tibial margin: their role in the prognosis of malleolar fractures. AB - One hundred forty-two patients with malleolar fractures were followed up for an average of 5.7 years postoperatively. In 80 cases (56.4%) we found no lesion of the distal articular surface of the tibia; 62 patients (43.6%) had a fracture of the posterior tibial margin. Both groups were closely matched with regard to fractures of the lateral and medial malleolus. The long-term results were significantly poorer when a fracture of the posterior tibial margin was additionally present, even in cases with a small marginal fragment of the lip of the tibia. Further, we found a clear relationship between the articular involvement and the incidence of post-traumatic osteoarthrosis in cases with no additional osteosynthesis of the fragment. In cases of larger fragments, the long term results after anatomic reduction and additional osteosynthesis were on the whole far better than in cases treated conservatively. PMID- 2585568 TI - Barbiturate therapy reduces nitrogen excretion in acute head injury. AB - The effect of pentobarbital on nitrogen and energy metabolism was evaluated in seven severely head-injured patients (Glasgow Coma Scale 4.7 +/- 1.7) within the first week postinjury. Measured energy expenditure (% of predicted) was significantly lower in the pentobarbital group (n = 4) versus control (n = 3) (76 +/- 23% versus 132 +/- 28%, respectively, p less than 0.01). Similarly, 24-hour urinary nitrogen excretion was lower for the barbiturate group compared to control (11.2 +/- 4.0 gm versus 19.5 +/- 3.3 gm, respectively, p less than 0.01). No statistical difference was noted for urinary 3-methylhistidine excretion between the barbiturate and control groups (43 +/- 12 mcg/day versus 47 +/- 14 mcg/day, respectively, p = N.S.). Barbiturate therapy decreases measured energy expenditure and reduces nitrogen excretion without significantly altering 3 methylhistidine excretion in head-injured patients. The metabolic effects of pentobarbital may enable the ability to achieve energy and nitrogen equilibrium during metabolic support of acutely head-injured patients. PMID- 2585570 TI - Closed Ender nailing of femur fractures in older children. AB - Twenty-eight patients ranging from 8 to 13 years old were treated at Childrens Hospital of Alabama for diaphyseal femur fractures. We studied two groups: 14 patients (Group I) were treated by conventional 90-90 balanced skeletal traction with late spica cast application; 14 patients (Group II) with multiple associated injuries or hyperkinetic problems were treated with closed retrograde Ender nailing. Groups I and II compared closely with regard to age, sex, fracture type and location, and mechanism of injury. The alignment, leg length, length of hospitalization, and length of therapy were analyzed. Our experience indicates that closed retrograde Ender nailing of diaphyseal femur fractures is an ideal technique where operative reduction and stabilization are indicated in older children. The technique yields results superior to conventional methods of treatment, with the advantage of early discharge from the hospital and return to school. PMID- 2585571 TI - In extremis use of staples for cardiorrhaphy in penetrating cardiac trauma: case report. AB - Patients in extremis following penetrating cardiac injury must be rapidly and effectively resuscitated. Treatment priorities are relief of tamponade with control of hemorrhage. Rapid closure of cardiac wounds is necessary to achieve hemostasis and preservation of cardiac function. A simple and rapid technique of emergency cardiorrhaphy is described utilizing the skin stapling device. PMID- 2585572 TI - The natural history of a traumatic vertebral artery aneurysm: case report. AB - A vertebral artery aneurysm resulting from stab wounds to the neck underwent spontaneous resolution during a period of observation. The natural history of such lesions appears to be previously undescribed. PMID- 2585573 TI - Neuroleptic malignant syndrome in a trauma patient: case report. AB - Presented is a case report of a multiple trauma patient whose post-traumatic course was complicated by neuroleptic malignant syndrome triggered by therapeutic haloperidol treatments. Once the syndrome was recognized and treated, a dramatic recovery was achieved. PMID- 2585574 TI - Unusual subclavian artery lacerations resulting from lap-shoulder seatbelt trauma: case reports. AB - While the impact of seatbelts on injury is favorable, their use is also associated with unique and previously unrecognized patterns of injury. Two cases of combined subclavian and vertebral artery injury, when lap shoulder harness restraints were used, are presented. PMID- 2585576 TI - Oral rehydration therapy in the 1990s. PMID- 2585575 TI - Major cerebral vessels injury caused by a seatbelt shoulder strap: case report. AB - Major cerebral arterial injury may result from penetrating or blunt trauma. In blunt trauma, clinical suspicion of such injury may not be raised, especially if the cranial CT scan is negative. We report a case of a seatbelt shoulder strap to the neck resulting in injury to three major cerebral vessels as demonstrated by cerebral angiography. Although the initial cranial CT scans were negative, a cerebral infarction ultimately developed. The patient was managed conservatively and recovered most of her functions. The importance of clinical suspicion and cerebral angiography is stressed. PMID- 2585577 TI - Viral meningitis and encephalitis in Saudi Arabia. AB - The laboratory confirmation of twelve clinically diagnosed cases of aseptic meningitis and encephalitis is described. Among three cases of aseptic meningitis one was due to mumps in a 14-month infant and the other two attributable to Cocksackie B-1. Herpes virus encephalitis due to HSV-1 was conclusively identified by IF monoclonal test from brain biopsy in tissue culture, and a further four cases also of HSV-1 encephalitis by virus isolation from CSF and presence of significant levels of herpes virus antibody in CSF and serum. Measles encephalitis was identified in four pediatric patients with one based on the isolation of measles virus from the CSF and in the other three with significant CSF/serum ratios to measles virus. PMID- 2585578 TI - Detection of cardiac problems among school children by health screening. AB - A study was undertaken to assess the types of cardiac diseases and dysrhythmias in a healthy population of 651,794 school children who underwent general health screening between January 1981 to December 1986. Congenital heart lesions were diagnosed in 1159 (0.18 per cent), the majority being mitral valve prolapse (MVP; 0.08 per cent), small ventricular septal defects (VSD; 0.04 per cent), mild pulmonary stenosis (PS; 0.03 per cent), and small atrial septal defects (ASD; 0.02 per cent). Other lesions detected were patent ductus arteriosus (PDA), coarctation of aorta (CoA), Fallot's Tetralogy (FT) and total anomalous pulmonary venous drainage (TAPVD). Of these, five had surgical closure of ASD, eight and ligation of PDA, and one had correction for TAPVD. Cardiac dysrhythmias were seen in 350 patients; consisting of premature ventricular contractions (PVC) in 186, right bundle branch block (RBBB) in 132, atrial ectopics (AE) in 17, sinus node dysfunction in five, atrioventricular (AV) block in seven, Wolff-Parkinson-White (WPW) syndrome in two, and paroxysmal atrial tachycardia (PAT) in one boy. Associated congenital heart lesions were found in 110 patients. The cardiac screening programme has resulted in a significant detection of cardiac abnormalities among apparently healthy school children. Early detection of cardiac disease has resulted in early remedial measures to be taken and thus improved cardiological care. PMID- 2585579 TI - Epidemiological and clinical features of rotavirus associated acute infantile diarrhoea in Cairo, Egypt. AB - Rotavirus was looked for in stool specimens from 200 randomly chosen infants and children aged 1-24 months presenting with acute diarrhoea of not more than 5 days duration at the Bab El-Sha'reya University Hospital during a 12-month period (January-December 1986). Forty per cent of cases were positive for rotavirus by the ELISA technique. Considering the seasonal pattern, during the hot months May to August, the monthly percentage of rotavirus positive cases ranged from 24 to 32 per cent while during the rest of the year, the range was from 37 to 60 per cent. There was no statistically significant difference between the rotavirus positive and negative cases as regards mean age in months (9.5 +/- 5.1 and 9.2 +/ 5.5, respectively), type of feeding or nutritional status. However, rotavirus positive cases were significantly more likely to present earlier, to have watery stools, to vomit or even to have vomiting before the onset of diarrhoea and to have respiratory symptoms. On the other hand, the means of dehydration score, rectal temperature and serum Na+ were not significantly different between the two groups. PMID- 2585580 TI - Toxoplasmosis in young Jamaicans. AB - Of 511 young (1-19 years of age) Jamaicans sampled for IgG antibodies to Toxoplasma by the ELISA method, there was an overall prevalence of 45 per cent. Seropositivity ranged from 24-26 per cent in the 2-year-olds, up to 54 per cent in the 5-9-year-olds. There was no significant difference in prevalence between the sexes, but there was a statistically significant difference between the rates from rural uplands (58 per cent), urban uplands (46 per cent), rural lowlands (40 per cent), and urban lowlands (32 per cent). PMID- 2585582 TI - Blood pressure profiles of a group of African children in the first year of life. AB - Systolic blood pressure was measured at birth, every week till 6 months, then every month till 12 months in normal Cameroonian neonates in the two Yaounde teaching hospitals. Systolic arterial pressure in awake babies rose from a mean of 65.1 +/- 1.30 mmHg at birth to 80.59 +/- 2.16 mmHg at 6 weeks; 94.39 mmHg at 12 months. The majority of this rise (7 mmHg) took place during the first 2 weeks of life. Systolic blood pressure increased by an average 2.5 mmHg weekly in the first 6 weeks, 0.5 mmHg weekly from 6 weeks to 6 months, and 0.6 mmHg monthly from 6 to 12 months. Relationships between systolic blood pressure and various parameters, and systolic blood pressures trends are analysed. Systolic blood pressure was not influenced by birth weight, sex of children, or tribe of parents. There was a weak correlation between systolic blood pressure and body weight between 6 weeks and 6 months. Systolic blood pressure measurements taken at different ages were not correlated. PMID- 2585581 TI - Postnatal weight gain of exclusively breast fed preterm African infants. AB - The weight of 64 preterm appropriate for gestational age infants were followed closely during the period of stay in the newborn unit. They were subdivided into three groups: A (1001-1250 g), B (1250-1500 g), and C (1501-1750 g). The mean gestation for these groups were 28.7, 30.5, and 31 weeks, respectively, while mean birth weights were 1132 +/- 81.7 g, 1377 +/- 85.6 g, and 1641 +/- 88.6 g. All were fed their own mothers breast milk during the period of study with no supplements. During the first week, there was significant weight loss in all groups as follows: A (12.0 per cent), B (7.7 per cent), and C (4.4 per cent). Thereafter, only group A lost weight in the second week, but the loss was not significant. Birth weights were regained at 23, 16, and 15 days, respectively. The weight gain after the initial loss was A (20.0 g), B (20.4 g), and C (20.2 g) per day. Group A had the fastest growth rate. PMID- 2585583 TI - Newborns vitamin A in relation to sex and birth weight. AB - Cord serum vitamin A values were determined in 256 male and 294 female neonates born in Tehran. The mean cord serum vitamin A values (micrograms/dl +/- SD) was 24.04 +/- 6.87 and ranged from 3.16 to 49.71 micrograms/dl. Males had significantly lower mean cord serum vitamin A values than females (P less than 0.001), and the prevalence of low serum vitamin A (below 20 micrograms/dl) was higher in male neonates than female ones (35 and 21 per cent, respectively). Serum retinol values increased gradually with birth weight. The mean serum vitamin A for premature neonates was significantly lower than term neonates. A significant r value for the linear correlation between cord serum retinol and parity was obtained for mothers aged more than 35 years. PMID- 2585584 TI - Physical growth of Chinese children from birth to 6 years old in urban and rural areas in 1985. AB - During 1985 a survey of the physical growth of 175,290 Chinese children less than 7 years in age was undertaken in the urban and rural areas of ten provinces. The results of weight, height, and head circumference are similar to those generally found as regards the differences between boys and girls. The children in rural areas were lighter and shorter. From the age of 3-6 months onwards the weights and heights of all groups were less than international standards. Nutrition is probably the major factor in these differences in growth. PMID- 2585585 TI - Field trial of TALC direct recording scale. PMID- 2585586 TI - Cerebrospinal fluid lactate and raised intracranial pressure in tuberculous meningitis. PMID- 2585587 TI - Pattern of pediatric gastrointestinal disorders in the eastern province of Saudi Arabia. PMID- 2585588 TI - Poliovirus infections in Saudi Arabia. PMID- 2585589 TI - Aetiological variables for low birth weight. PMID- 2585590 TI - Sudden unilateral sensorineural hearing loss: a syndrome or a symptom? AB - In 122 patients with sudden unilateral sensorineural hearing loss, no apparent cause was identified in 88 cases. In these idiopathic cases, gender did not affect the age distribution and age did not affect the range of most affected frequencies or the severity of hearing loss. Vertigo at onset of the disease was not a sign of poor prognosis. Cases in the idiopathic group could, generally, be distinguished into two groups: (1) cases with hearing loss affecting all (with one exception) or mainly the high frequencies and symptomatology reminiscent of known types of cranial (poly)neuritis; (2) cases with hearing loss affecting mainly the low frequencies and symptomatology reminiscent of Meniere's disease. These data suggest that there may be certain pathophysiologic similarities in these cases with: (a) cranial (poly)neuritis if all or mainly the high frequencies are affected; (b) Meniere's disease if the low frequencies are mainly affected. PMID- 2585591 TI - Tourette syndrome and otolaryngology. AB - Tourette syndrome (TS) is the most complex tic disorder and presents primarily in the pediatric population between the ages of two and 15. The otolaryngologist may be consulted to see such a patient because of head and neck or facial tics or more often because of phonic or vocal tics such as throat-clearing, sniffing, coughing or abnormal noises. As this disorder has not appeared in the otolaryngologic literature we undertook a retrospective chart review (N = 72) and follow-up questionnaire related to the otolaryngologic aspects of this disorder. PMID- 2585593 TI - The Le Fort I maxillary osteotomy approach to surgery of the skull base. AB - A new modification of the transoral route involving a Le Fort I maxillotomy has been developed to offer much-improved exposure of the midline skull base. The procedure involves a standard Le Fort I osteotomy combined with division of the nasal septum and lateral pterygoid laminae, and excision of the inferior turbinates and vomer. With insertion of a modified Dingman gag, exposure is gained from the pituitary fossa to the arch of the atlas. The approach has been successfully employed to resect eight different skull base lesions, both intracranially and extracranially, in 20 operations involving 17 patients. Complications and morbidity were minimal. Postoperative cosmetic results and occlusion were excellent. The Le Fort I maxillotomy approach has distinct advantages in dealing with a whole spectrum of pathology around the clivus and postnasal space. PMID- 2585592 TI - Assessment of laryngeal cancer: CT scan versus endoscopy. AB - In order to assess the value of the systematic use of CT scan in the workup for laryngeal cancer, a retrospective study was conducted on 66 consecutive previously untreated cases of laryngeal cancer. Endoscopic and CT scan findings were systematically compared. The areas of particular difficulty in CT scan assessment are described. CT scan alone understaged laryngeal cancers in 10.6% of cases, all of them being superficial spreading tumors within the larynx or in the juxtalaryngeal areas. CT scan worsened the staging in 22.7% of cases, all of them being deep invasions overlooked by endoscopy. CT was most useful in lesions initially classified as T2 and T3, which included all those reclassified by CT. None of the T1 lesions was upgraded after CT, and systematic use of CT for this stage is not warranted. CT scan workup changed the therapeutic attitude in 10 of the 66 patients (15.1%), causing a switch to conservative surgery in seven patients and total laryngectomy with radiotherapy for the three others. CT was also valuable in choosing the most suitable technique for conservation surgery. PMID- 2585594 TI - Resection of the extra cranial carotid artery in head and neck cancer. AB - Carotid artery resection and reconstruction by unreversed autogenous saphenous vein grafting was undertaken in six patients undergoing extensive resection for malignancy over a four-year period. There were two deaths within 30 days of operation: one from secondary hemorrhage and one from bronchopneumonia. One patient died at six months and one at three months from recurrence, one died at 12 months from recurrence and one died free of disease at 10 months from aspiration. Vascular complications in three patients included a single TIA at 14 days, graft thrombosis with hemiplegia and a secondary hemorrhage from the graft requiring graft ligature with a subsequent normal neurological status. Malignant involvement of the extracranial carotid artery is associated with poor survival. Treatment by carotid artery resection and grafting should be considered in such cases, particularly where the pharynx or oral cavity are not entered. PMID- 2585595 TI - The immediate role of the dentist in the maxillectomy patient. AB - It is imperative that comprehensive planning takes place for the potential maxillectomy patient. Input from the dentist is required for all stages of the procedure, from initial consultation to placement of the final prosthesis. By utilizing an interim dental prosthesis (splint), the impact of tissue loss, wound fibrosis and neurological damage can be minimized. In this paper, the authors address the initial stage in the treatment sequence, the surgical splint. PMID- 2585596 TI - Parathyroid cysts. AB - Parathyroid cysts are relatively uncommon lesions. Approximately 200 cases have been reported. Despite their location in the region of the thyroid gland, they have not previously been discussed in the otolaryngologic literature. They arise from remnants of the pharyngeal pouch or as a result of cystic degeneration of a parathyroid adenoma. A case of a parathyroid cyst occurring in a 13-year-old female is presented. This is the youngest case ever reported. Fine needle aspiration of an anterior neck mass yielded clear fluid, a finding highly suggestive of a parathyroid cyst. Radioimmunoassay of the fluid demonstrated a high level of parathormone and low level of thyroglobulin concentration, thereby confirming the diagnosis. In this case, which was diagnosed by FNA, the need for a trial of thyroid hormone suppression or hemithyroidectomy was obviated. PMID- 2585597 TI - Cervical esophageal perforation caused by diagnostic flexible esophagoscopy. AB - Two cases of iatrogenic cervical esophageal perforation caused by diagnostic flexible fiberoptic endoscopy are described. The relative risks of perforation at fiberoptic and rigid esophagoscopy are discussed and the importance of contrast radiology and early diagnosis are emphasized. Cases with a small tear and minimal contamination may be treated conservatively. Early surgical repair with drainage is otherwise the treatment of choice for cervical esophageal perforation. Even if there has been abscess formation tracking down into the mediastinum, drainage can be successfully achieved via the neck, avoiding the need for thoracotomy. PMID- 2585598 TI - How I do it: a simple and inexpensive method to collect bone chips. PMID- 2585599 TI - Replication-dependent activation of the adenovirus major late promoter is mediated by the increased binding of a transcription factor to sequences in the first intron. AB - During lytic infection, the adenovirus major late promoter (MLP) is primarily activated after the onset of viral DNA replication. Using a combination of DNA binding and in vitro transcription assays, we delineated a discrete MLP element spanning positions +80 to +106 which is essential for the replication-dependent activation of this promoter. We also identified a 40-kilodalton protein (the downstream element factor [DEF]) which binds to the +86-TTGTCAGTTT-+95 motif within this element. Whereas the DEF-binding activity is barely detectable in uninfected cells, it is readily visualized in adenovirus-infected cells, but only after the onset of viral DNA replication. Preventing the interaction of DEF with the MLP template impairs the in vitro transcriptional stimulation. We conclude that this replication-dependent activation of the MLP is, at least in part, mediated by induction of the specific binding of DEF to the MLP downstream element. PMID- 2585600 TI - Adenoviruses with nonidentical terminal sequences are viable. AB - Adenovirus genomes consist of linear DNA molecules containing inverted terminal repeat sequences (ITRs) of 100 to 200 base pairs. The importance of identical termini for viability of adenoviruses was investigated. The viral strains used in this study were wild-type adenovirus type 5 (Ad5) and a variant Ad2 strain with termini which were distinct from those of all other human adenoviruses sequenced to date. A hybrid virus (sub54), obtained by recombination between Ad2 and Ad5, derived the left 42 to 52% of its genome from Ad2 and the right 58 to 48% from Ad5. Southern blotting analysis with labeled oligodeoxynucleotides indicated that both Ad2 and Ad5 ITRs were present in sub54 viral DNA preparations, and successive plaque purifications of sub54 demonstrated that viruses with nonidentical terminal sequences were viable but were rapidly converted to viruses with identical ends. Cloning of the sub54 genome as a bacterial plasmid supported the observations made by analysis of sub54 virion DNA. A plasmid, pFG154, was isolated which contained the entire adenovirus genome with an Ad2 ITR at the left terminus covalently linked to an Ad5 ITR at the right terminus. Upon transfection of mammalian cells with pFG154, viral progeny were obtained which had all possible combinations of termini, thus confirming that molecules with nonidentical termini are viable. Pure populations of viruses with nonidentical termini could not be isolated, suggesting efficient repair of one end with the opposite terminus used as a template. A model for this process is proposed involving strand displacement replication and emphasizing the importance of panhandle formation (annealing of terminal sequences) as a replicative intermediate. PMID- 2585601 TI - Promoter analysis of influenza virus RNA polymerase. AB - Influenza virus polymerase, which was prepared depleted of viral RNA, was used to copy small RNA templates prepared from plasmid-encoded sequences. Template constructions containing only the 3' end of genomic RNA were shown to be efficiently copied, indicating that the promoter lay solely within the 15 nucleotide 3' terminus. Sequences not specific for the influenza virus termini were not copied, and, surprisingly, RNAs containing termini identical to those from plus-sense cRNA were copied at low levels. The specificity for recognition of the virus sense promoter was further defined by site-specific mutagenesis. It was also found that increased levels of viral protein were required in order to catalyze both the cap endonuclease-primed and primer-free RNA synthesis from these model templates, as well as from genomic-length RNAs. This finding indicates that the reconstituted system has catalytic properties very similar to those of native viral ribonucleoprotein complexes. PMID- 2585603 TI - Transport of hepatitis B virus precore protein into the nucleus after cleavage of its signal peptide. AB - The precore and core proteins of hepatitis B virus have identical deduced amino acid sequences other than a 29-residue amino-terminal extension (precore region) on the precore protein. The first 19 of these residues serve as a signal sequence to direct the precore protein to the endoplasmic reticulum, where they are cleaved off with formation of precore protein derivative P22 for secretion. In this report, we show that P22 can alternatively be transported into the nucleus following signal peptide cleavage. Experiments with deletion mutants indicated that this nuclear transport proceeds via the cytosol and is dependent on the amino-terminal portion of P22. Thus, the hepatitis B virus precore protein is a secreted, cytosolic, and nuclear protein. PMID- 2585602 TI - Mutations that affect phosphorylation of the adenovirus DNA-binding protein alter its ability to enhance its own synthesis. AB - The multifunctional adenovirus single-strand DNA-binding protein (DBP) is highly phosphorylated. Its phosphorylation sites are located in the amino-terminal domain of the protein, and its DNA- and RNA-binding activity resides in the carboxy-terminal half of the polypeptide. We have substituted cysteine or alanine for up to 10 of these potential phosphorylation sites by using oligonucleotide directed mutagenesis. Alteration of one or a few of these sites had little effect on the viability of virus containing the mutated DBP. However, when eight or more sites were altered, viral growth decreased significantly. This suggests that the overall phosphorylation state of the protein was more important than whether any particular site was modified. The reduction in growth correlated with both depressed DNA replication and expression of late genes. This reduction was probably the result of lower DBP accumulation in mutant-infected cells. Interestingly, although the stability of the mutated DBP was not affected, DBP synthesis and the level of its mRNA were depressed 5- to 10-fold for the underphosphorylated protein. These results suggest that DBP enhances its own expression and imply that phosphorylation of the DBP may be important for this function. Similarities to several eucaryotic transcriptional activators, which are composed of negatively charged activating domains and separate binding domains, are discussed. PMID- 2585604 TI - Steady-state infection by echovirus 6 associated with nonlytic viral RNA and an unprocessed capsid polypeptide. AB - We established a human cell line which was persistently infected (PI) by the normally cytolytic echovirus 6. All of the cultured PI cells contained genome size viral RNA which was synthesized continuously and incorporated into virus particles. This steady-state infection has been maintained for more than 6 years. In contrast to RNA of wild-type echovirus 6, the viral RNA from PI cells was not lytic when transfected into uninfected, susceptible cells. The capsid polypeptides of the virus particles produced during lytic infections were compared with those of virus particles from PI cells. Wild-type virions contained five polypeptides with molecular masses of 31.5, 27, 25.8, 21.2, and 9.5 kilodaltons. Comparison of polypeptide profiles of virions and empty immature capsids along with peptide analyses by immunoblotting and partial proteolysis of isolated viral proteins identified the cleavage products of the 31.5-kilodalton polypeptide (VP0) as the two smaller polypeptides (VP2 and VP4). The virus particles produced by PI cells as well as cellular extracts of PI cells contained only the three largest proteins (VP0, VP1, and VP3), indicating that VP0 was not processed during persistent infection. The lack of VP2 and VP4 in the defective virus particles coincided with their inability to attach to uninfected, susceptible cells. The maintenance of the steady-state infection of echovirus 6 was not dependent upon the release of virus particles from PI cells. PMID- 2585605 TI - Interactions between nuclear factors and the hepatitis B virus enhancer. AB - We have previously established that the tissue-specific activity of the hepatitis B virus (HBV) enhancer is mediated by trans-acting cellular factors. Here we have studied in vitro the interactions between the HBV enhancer DNA and cellular factors present in nuclear extracts from both liver and nonliver cell types. The results presented in this study imply the involvement of several distinct, ubiquitous, and liver-specific cellular factors with the HBV enhancer. Sequence analysis of the binding sites for these proteins on HBV DNA showed homologies to sequence motifs known to bind other previously characterized and purified transcription factors including CAAT/enhancer-binding protein. Thus, all of these binding sites may function in concert to activate liver-specific transcription of HBV genes from their respective promoters. PMID- 2585606 TI - Defined mutations in a small region of the brome mosaic virus 2 gene cause diverse temperature-sensitive RNA replication phenotypes. AB - The central portion of the brome mosaic virus (BMV) 2a protein represents the most conserved element among the related RNA replication components of a large group of positive-strand RNA viruses of humans, animals, and plants. To characterize the functions of the 2a protein, mutations were targeted to a conserved portion of the 2a gene, resulting in substitutions between amino acids 451 and 484. After the temperature profile of wild-type BMV RNA replication was defined, RNA replication by nine selected mutants was tested in barley protoplasts at permissive (24 degrees C) and nonpermissive (34 degrees C) temperatures. Four mutants did not direct RNA synthesis at either temperature. Various levels of temperature-sensitive (ts) replication occurred in the remaining five mutants. For two ts mutants, no viral RNA synthesis was detected at 34 degrees C, while for two others, an equivalent reduction in positive- and negative-strand RNA accumulation was observed. For one mutant, positive-strand accumulation was preferentially reduced over negative-strand accumulation at 34 degrees C. Moreover, this mutant and another displayed preferential suppression of genomic over subgenomic RNA accumulation at both 24 and 34 degrees C. The combination of phenotypes observed suggests that the 2a protein may play a role in the differential initiation of specific classes of viral RNA in addition to a previously suggested role in RNA elongation. PMID- 2585607 TI - Evidence for specificity in the encapsidation of Sindbis virus RNAs. AB - We investigated the interaction of the capsid protein of Sindbis virus with Sindbis viral RNAs and defined a region of the genome that is required for binding in vitro and for packaging in vivo. The binding studies were performed with purified capsid protein immobilized on nitrocellulose and 32P-labeled RNAs transcribed in vitro from viral and nonspecific cDNAs. Genomic and defective interfering (DI) RNAs bound capsid protein significantly better than either the subgenomic (26S) RNA or nonspecific RNAs. Transcripts prepared from either truncated or deleted cDNAs were used to define the segment required for binding. This segment, which is represented twice in DI RNA, lies between nucleotides 746 and 1226 of the genomic RNA and is within the coding region of the nonstructural protein nsP1. Insertion of a domain covering these sequences into a nonviral RNA was able to convert it from a background level of binding to an activity that was 80% that of the Sindbis virus DI RNA. We analyzed DI RNA transcripts in detail because they could be studied not only for the ability to bind capsid protein in vitro but also for the ability to be replicated and packaged in vivo in the presence of helper virion RNA. The results obtained with three DI RNAs are reported. One (CTS14), which has one copy of the binding domain, bound efficiently to capsid protein in vitro and was packaged in vivo as measured by amplification on passaging. In contrast, a DI RNA (CTS1) which lacked this region did not bind to capsid protein and was not detected on passaging. By using lipofectin (P. L. Felgner, T. R. Gadek, M. Holm, R. Roman, H. W. Chan, M. Wenz, J.P. Northrop, G. M. Ringold, and M. Danielson, Proc. Natl. Acad. Sci. USA 84:7413-7417, 1987) to enhance RNA uptake, we were able to demonstrate that CTS1 RNA was replicated in the transfected cells. It was replicated to the same level as another DI RNA (CTS253) which has only the 3' 279 nucleotides of the binding domain and these are located near the 3' terminus of the RNA. CTS253 bound capsid protein to an intermediate level but was amplified on passaging. The binding studies and the in vivo packaging data, taken together, provide strong support for the conclusion that there is a specific capsid recognition domain in Sindbis virus RNA that plays a role in nucleocapsid assembly. PMID- 2585608 TI - The c-cbl proto-oncogene is preferentially expressed in thymus and testis tissue and encodes a nuclear protein. AB - Cas NS-1 is an acutely transforming murine retrovirus that induces early B lineage lymphomas and occasional myeloid leukemias. The transforming sequence of this virus, v-cbl, shows no homology to known oncogenes but has some similarities to the yeast transcriptional factor GCN4. In this study we used a v-cbl probe to analyze mRNAs from a wide range of murine and human hemopoietic tumor cell lines and detected an 11-kilobase mRNA in all lineages. In normal mouse tissues the expression of c-cbl was highest in testis and thymus tissues, the predominant species in testis tissue being a 3.5-kilobase mRNA. The v-cbl oncogene was inserted into a bacterial expression vector to produce protein for the immunization of rabbits. Affinity-purified v-cbl antibodies identified abundant levels of p100gag-cbl in Cas NS-1-transformed fibroblasts and lower levels of a 135-kilodalton protein (p135c-cbl) in both normal and transformed cells. Subcellular fractionation showed that p100gag-cbl and p135c-cbl are both located in the nucleus and retained following 420 mM salt extraction. These results indicate that the translational product of a c-cbl is a 135-kilodalton nuclear protein. PMID- 2585609 TI - Transcriptional analysis of minute virus of mice P4 promoter mutants. AB - A series of 5' deletion, internal deletion, and linker-scanning mutants of the minute virus of mice P4 promoter were constructed and analyzed for transcriptional activity in nuclear extracts of mouse A92L fibroblasts. A GC box and a TATA box essential for in vitro transcription from the P4 promoter were localized between nucleotides 150 and 180 (-55 to -25 relative to the primary RNA start site). Although this region also exhibited homologies to other transcriptional control elements, the simian virus 40 enhancer, and the adenovirus E1A enhancer, only the GC box and TATA box appear functional. These two motifs also play an essential role in vivo, although additional upstream sequences (between -139 and -55) are required for optimal transcription. DNase I footprinting, competitive gel retardation assays, and UV-photocrosslinking were used to identify Sp1-like proteins of 95 and 120 kilodaltons in A92L extracts that interact with the GC box of the minute virus of mice P4 promoter. PMID- 2585610 TI - Permanent cell lines that show temperature-dependent expression of adenovirus virus-associated RNA. AB - Temperature-sensitive COS cells, clone E540, have been stably transformed at a restrictive temperature with plasmid pVA1, which contains the adenovirus type 5 virus-associated (VA) genes in addition to the Neor marker. Transformed cell clones, named EVA cells, contained adenovirus DNA in an integrated form while grown at restrictive temperature but accumulated up to 100 to 200 copies of the input plasmid per cell after temperature shift down. Concomitant with this gene amplification, an accumulation of VA RNA was observed, reaching average concentrations of 10(4) to 10(5) copies per cell. The VA RNA synthesized in EVA cells is functional, as judged by inhibition of in vitro eucaryotic initiation factor-2 phosphorylation and enhancement of reporter gene expression. These EVA cell lines may be of use to study the mechanism of VA RNA function in the absence of adenovirus infection. PMID- 2585611 TI - Internal entry of ribosomes and ribosomal scanning involved in hepatitis B virus P gene expression. AB - The recent demonstration that the synthesis of duck hepatitis B virus (HBV) reverse transcriptase does not require translational frameshifting and the finding that poliovirus mRNA translation occurs in a cap-independent manner by internal binding of ribosomes in the 5' noncoding region led us to design experiments to test the hypothesis of internal entry of ribosomes on C gene mRNA for HBV P gene expression. We show that in human cells, translation can be initiated at the first AUG of the HBV P gene by entry of ribosomes in a region located upstream of the P gene. Moreover, the leaky scanning of ribosomes observed on the first AUG of the HBV P gene could be responsible for the synthesis of the two forms of reverse transcriptase described for HBV particles. PMID- 2585613 TI - Extracorporeal shock wave lithotripsy as monotherapy of staghorn renal calculi: 3 years of experience. AB - From May 1985 to February 1988, 61 patients with renal staghorn calculi (41 with incomplete C4 and 20 with complete C5 lesions) underwent extracorporeal shock wave lithotripsy monotherapy. Of the patients 37 were treated without preoperative Double-J* stenting, while 24 underwent Double-J stenting before extracorporeal shock wave lithotripsy. Of the patients with incomplete staghorn calculi (C4) and a preoperative ureteral stent 85% were free of stones after 6 months in contrast to only 52.4% of those without a stent and 85.7% of those with infected C4 calculi who underwent preoperative stenting. Hospitalization decreased from 17.7 days in patients without a stent to 14.2 days after stenting, followed by the number of auxiliary procedures (nephrostomy, Zeiss loop and ureteroscopy) and postoperative complications. Complete staghorn calculi (C5) without a preoperative stent had the smallest success rate of stone elimination: only 43.7% of the patients were free of stones after 6 months with a rehospitalization rate of 62.5%. For incomplete staghorn renal calculi (C4) extracorporeal shock wave lithotripsy monotherapy with a preoperative Double-J stent is the noninvasive method that offers excellent stone elimination (85%), comparable to the results of percutaneous nephrolithotripsy (with or without complementary extracorporeal shock wave lithotripsy) and anatrophic nephrolithotomy. PMID- 2585612 TI - Generalized and localized biased hypermutation affecting the matrix gene of a measles virus strain that causes subacute sclerosing panencephalitis. AB - The matrix (M) genes of Yamagata-1 strain subacute sclerosing panencephalitis virus passaged in African green monkey kidney cells and human neuroblastoma cells displayed strikingly nonrandom sequence divergence. The genes of both substrains shared a large number of uridine (U) to cytidine (C) transitions, but the latter contained numerous additional U to C changes in a localized region. Over 90% of the additional mutations were identical to the hypermutated nucleotides in the M gene found in a measles inclusion body encephalitis case. The nonrandom nature, the apparent host dependency, and the abrupt boundaries of these mutations suggest that these mutations might be caused by an extrinsic biased mutational activity rather than intrinsic polymerase errors. This mutational activity might account for the extraordinarily high C to U ratios in the non-protein-coding regions of both the M and fusion genes of wild-type measles virus. PMID- 2585614 TI - Lessons learned in patients with large steinstrasse. AB - Experience with 19 patients (25 ureters) who suffered the complication of a large steinstrasse (a third or more of the ureteral length) has led to lessons regarding the management of this complication as well as to insights into patient presentation, metabolic consequences, and the efficiency of diagnostic and therapeutic modalities. Few symptoms were present in a large percentage of patients despite urinary obstruction, decreased renal function, infection and in several cases impending sepsis. Large stone burdens, bilateral treatment, inability to debulk stone burden before extracorporeal shock wave lithotripsy and unexpected fragment movement were definite predisposing factors in the development of this complication. Double pigtail stents and percutaneous nephrostomy alone did not always prevent or resolve the problem. Combined use of percutaneous nephrostomy and ureteroscopic ultrasonic or laser lithotripsy appears to be the most effective treatment modality in patients who fail brief observation. This approach can be combined under appropriate circumstances with a secondary extracorporeal shock wave lithotripsy or percutaneous nephrolithotripsy treatment in the staged management of complex upper urinary tract calculous disease. PMID- 2585615 TI - Choice of an optimal diluent for intravesical bacillus Calmette-Guerin administration. AB - The physical conditions, including diluent pH, salt concentration and duration of bacillus Calmette-Guerin attachment, were determined in in vitro binding assays for soluble and matrix fibronectin. Since soluble fibronectin may block attachment of bacillus Calmette-Guerin to matrix fibronectin in the bladder, the optimal conditions were determined under which matrix fibronectin-bacillus Calmette-Guerin binding was maximal and soluble fibronectin-bacillus Calmette Guerin binding was minimal. These conditions, which were confirmed in vivo in the murine bladder model, included use of normal saline, pH 7 as diluent for bacillus Calmette-Guerin organisms, with retention of the bacillus Calmette-Guerin suspension for 2 hours. PMID- 2585616 TI - Comparative flow cytometric deoxyribonucleic acid studies on exophytic tumor and random mucosal biopsies in untreated carcinoma of the bladder. AB - In 290 patients with untreated carcinoma of the bladder the deoxyribonucleic acid properties, as measured by flow cytometry, of 3 random mucosal biopsies were studied and compared to those of the exophytic tumors. Mucosal aneuploidy was found with few exceptions in aneuploid tumors only, and in a significantly lower frequency in aneuploid tumors of grade 2 than grade 3. The individual specificity of bladder tumors is emphasized by the observation that the level of ploidy was mostly the same in aneuploid mucosal biopsies as in the exophytic tumor. This is underlined further by the occurrence of cell populations of the same ploidy in different parts of the bladder mucosa. However, S-phase values of the concomitant intraurothelial lesions were significantly lower than those of the exophytic tumors. Therefore, we concluded that the process of evolution from malignantly transformed lesions, confined to the urothelium, to an exophytic or invasive tumor is dependent on a further elevated proliferation of the urothelial lesions. PMID- 2585618 TI - Mayo Clinic experience with use of the AMS800 artificial urinary sphincter for urinary incontinence following radical prostatectomy. AB - The model AMS800 artificial urinary sphincter was implanted in 117 patients with urinary incontinence resulting from radical prostatectomy. The indication for implantation was total incontinence in 107 patients and stress incontinence in 10. All patients had bulbous urethral cuff insertion and 20 had previous pelvic irradiation. Followup questionnaire indicated a 90% significantly improved continence rate and a 90% satisfaction rate among patients. There were 64 surgical revisions required in 37 patients: inadequate cuff compression in 21 (33%), tubing kinks in 10 (16%), urethral cuff erosion in 8 (13%), scrotal hematoma in 6 (9%), control assembly malfunction in 4 (6%) and cuff leaks in 4 (6%). Of the 20 patients with previous pelvic radiation 2 (10%) had at least 1 erosion, compared to 5 of 97 (5%) in the nonirradiated group. At followup 5 patients did not have at least 1 component of the AMS800 device indwelling (2 cuffs and 3 entire devices had been removed). PMID- 2585617 TI - Radical radiotherapy for muscle invasive transitional cell carcinoma of the bladder: failure analysis. AB - Patients with muscle invasive carcinoma of the bladder treated with radical radiation were prospectively documented and followed in an attempt to identify prognostic factors predictive of the response to treatment. Data on 121 consecutive patients treated with radical radiation between 1981 and 1985 are presented. Over-all actuarial survival of the patient population (median age 70 years) was 31.6% at 5 years and cause-specific survival was 44.8%. At analysis 33 of 121 patients (27.3%) were alive with preserved bladder function. Independent prognostic factors for cause-specific survival and for complete response with radical radiation were tumor configuration, hemoglobin level and clinical stage. The rate free of local relapse was significantly influenced by stage and presence of coexistent carcinoma in situ. The study suggests that factors other than stage and grade influence prognosis in invasive bladder cancer and should be considered in interpreting treatment results. PMID- 2585619 TI - Kaposi's sarcoma of the penis in patients with acquired immunodeficiency syndrome. AB - With the growing number of patients with the acquired immunodeficiency syndrome there has been a marked increase in the incidence of Kaposi's sarcoma. Kaposi's sarcoma of the penis was the initial presenting manifestation of acquired immunodeficiency syndrome in 4 patients. Overall, less than 3% of all acquired immunodeficiency syndrome patients with Kaposi's sarcoma have the initial lesion on the penis. However, eventually almost 20% of those with Kaposi's sarcoma will have lesions on the genitalia. Therefore, urologists must have an understanding of the entity and its management. A conservative approach to treatment of these lesions is recommended. PMID- 2585620 TI - The role of ilioinguinal lymphadenectomy and significance of histological differentiation in treatment of carcinoma of the penis. AB - We reviewed retrospectively the medical records of 58 patients treated for squamous cell carcinoma of the penis who were followed for more than 3 years or until they died. Tissue sections from all patients were reviewed. Of 15 patients with stage I disease 11 underwent partial penectomy, and 4 underwent partial penectomy and immediate ilioinguinal lymphadenectomy; none died of cancer. Nine patients with stage II and 9 with stage III disease underwent partial or total penectomy and immediate ilioinguinal lymphadenectomy, and 5-year survival was 100 and 75%, respectively. Of 20 patients with clinical stage II disease who did not undergo immediate ilioinguinal lymphadenectomy 18 had metastasis to the groin. Of these 18 patients 12 underwent delayed ilioinguinal lymphadenectomy but only 1 survived more than 5 years. We evaluated the possible significance of the degree of histological differentiation of the primary tumor to the course of the disease. Of the 23 cases of carcinoma in situ or well differentiated disease only 1 became metastatic, while of the 35 cases of moderately to poorly differentiated disease 31 metastasized to the groin. Vascular invasion of cancer cells in the primary tumor was another indicator for poor prognosis. PMID- 2585621 TI - Predictors of success in electroejaculation of spinal cord injured men. AB - Rectal probe electroejaculation was attempted in 48 spinal cord injury men and greater than 10 million sperm were obtained in 71%. Patient age and interval since injury had no effect on outcome. The best performance was seen in thoracic paraplegics and in those using intermittent catheterization for bladder management. Indwelling urethral catheters and high pressure reflex voiding had a negative impact on electroejaculation results. PMID- 2585622 TI - Psychological aspects of testis cancer therapy: a prospective study. AB - We examined the impact of testis cancer and its curative therapies on the outlook of life, working activity, partner relationship and sexual function in 31 consecutive patients 18 to 51 years old (mean age 29.3 years, median 28 years) who already had undergone orchiectomy. Of the patients 13 subsequently were treated with chemotherapy alone, 6 with retroperitoneal lymph node dissection alone, and 7 with chemotherapy and an operation, while 5 seminoma patients were treated with radiotherapy. The patients were examined 3, 6 and 18 months after orchiectomy. Each patient was required to fill out a questionnaire to gather information relative to their work activities, emotional relationship with the partner and sexual life. The patients also completed an assessment form on the quality of life (Spitzer QL-Index) and a series of horizontal analogues to evaluate anxiety, mood, nausea, weakness and general health status. The statistical analysis of the linear and quadratic components for the variables under study was done with the general linear model for block design. Psychosocial adaptability of these patients, regardless of the treatment they underwent, in time became progressively less problematic and the development of psychosocial problems during the long-term adjustment was low. Only 2 patients reported worsening of the emotional relationship with the partner after treatment: 1 underwent chemotherapy and an operation, and 1 underwent radiotherapy. With regard to sexual life, no serious dysfunction was noted apart from the loss of ejaculation in 11 of 13 patients who underwent retroperitoneal lymph node dissection. Of our sample patients who had lost ejaculation only 2 suffered from a high state of anxiety. The anxiety scores on the last completed linear analogue were 2.6 and 4.1, whereas at the same time the mood scores were 1.9 and 4.4. Therefore, it is important for the clinician to assess the psychogenic aspect of this side effect when this type of operation is proposed. PMID- 2585623 TI - Complications of therapy for testicular cancer. AB - Of 244 patients with testis cancer seen between January 1970 and December 1987 (mean followup 70 months) 88 (36.1%) experienced 1 or more early complications (within 1 year), while 16 (6.6%) had a late (greater than 1 year) complication. Chemotherapy-related complications occurred in 55 of 141 patients (39%), including 6 (4.3%) treatment-related deaths. Chemotherapy-related complications were correlated to the initial extent of disease (p equals 0.021) and to more than 4 cycles of cisplatin-based therapy (p equals 0.001). Retroperitoneal lymphadenectomy-related complications occurred in 48 of 148 patients (32.4%) without surgical mortality and were not statistically increased in those performed after chemotherapy. Kidney loss occurred in 6 patients (4.1%) after retroperitoneal lymphadenectomy. Nine of 110 patients (8.2%) treated with radiotherapy experienced an early therapy-related complication, while late complications included 3 gastrointestinal strictures requiring surgical intervention 8 to 10 years after radiotherapy. Only 1 secondary malignancy (other than contralateral testis cancer) was discovered in this review. Initial extent of disease was the best predictor for over-all complication rate and higher over all complications were noted in the cisplatin era (1979 to 1987) but these associations were not necessarily present for complication rates of individual therapies. PMID- 2585625 TI - Transurethral incision of the prostate: a preoperative and postoperative analysis of symptoms and urodynamic findings. AB - The efficacy of transurethral incision of the prostate was evaluated prospectively in 26 men with urodynamic evidence of outlet obstruction secondary to small prostate glands (estimated size less than 30 gm). All men completed preoperative and postoperative symptom questionnaires and extensive urodynamic testing with a median postoperative followup of 16.25 months. There was a significant improvement in subjective symptom analysis and objective urodynamic parameters (peak and mean uroflow rates, maximal detrusor pressure at peak flow, volume at first urge and post-void residual volume) as a result of transurethral incision of the prostate with minimal postoperative morbidity. Antegrade ejaculation was preserved in 55% of the men with normal preoperative ejaculation. Based on subjective and objective criteria, transurethral incision of the prostate is an effective treatment option for selected men with outlet obstruction. PMID- 2585624 TI - Phenol sclerotherapy for hydrocele: a study in 55 patients. AB - Sclerotherapy with 2.5% phenol solution was used to treat 63 hydroceles in 55 patients with a mean age of 69 years. In 51.6% of the patients (32 hydroceles) 1 treatment was sufficient, while 2 treatments were necessary in 25.8% (16 hydroceles), 3 in 13% (8 hydroceles) and 4 in 8% (5 hydroceles). One patient required 7 injections. Treatment was unsuccessful in 1 patient in whom a local allergic reaction developed. Only 1 patient complained of pain, and other complications were rare and mild. On the basis of this experience we concluded that sclerotherapy with phenol 2.5% is a painless, highly effective, safe and economical procedure that permits one to avoid an operation, anesthesia and hospitalization. Its use is warranted in adults and particularly in the elderly. PMID- 2585626 TI - Urinary tract stone disease in the United States veteran population. I. Geographical frequency of occurrence. AB - The geographical distribution of hospitalization for urinary tract stone disease in the continental United States has been studied in the United States veteran population. The current study has been facilitated by the availability of a centralized computer data base containing the International Classification of Disease Codes for all hospital discharges at all Veterans Administration medical facilities. These data have allowed for an accurate mapping of the hospital discharge rate for urinary tract stone disease (stone discharge rate) in a population at risk for urolithiasis. Stone discharge rate data have been compared to those from the 2 previous studies conducted in general hospitals in 1952 and 1974. The stone discharge rate was 7.9 +/- 3.4 in 1952, 9.97 +/- 2.82 in 1974 and 7.58 +/- 2.01 in our study. These data indicate that the urinary tract stone discharge rate has not markedly varied during the last 34 years and also that the southeastern states still evidence the highest hospital discharge rate for urinary tract stone disease. PMID- 2585627 TI - Urinary tract stone disease in the United States veteran population. II. Geographical analysis of variations in composition. AB - The geographical distribution of crystalline components observed in urinary tract stones in the continental United States has been studied in the United States veteran population. Since the veteran population is at risk for urolithiasis the National Veterans Administration Crystal Identification Center was established in 1983 for the characterization of all crystal-containing veteran patient samples using high resolution x-ray powder diffraction. The geographical distribution of whewellite, weddelite, apatite, brushite, struvite, uric acid and uric acid dihydrate is presented. The percentage occurrence of the crystalline components, percentage occurrence of admixed stones and geographical distribution of the number of components in admixed stones also are presented. The data highlight that although the southeastern United States has the highest patient discharge rate for stones, this high discharge rate appears to be correlated specifically with a high discharge rate for calcium oxalate stones and not with a high discharge rate for any of the other common stone components. PMID- 2585628 TI - Spiral gonadal vein graft extension of right renal vein in living renal transplantation. AB - A spiral graft fashioned from the gonadal vein was used to lengthen a short renal vein successfully in a living renal transplant. PMID- 2585629 TI - Ureteral irrigation during ureteroscopy: the rapid infusion system. AB - The use of a rapid infusion system during ureteroscopy has facilitated introduction of the ureteroscope into the ureter and has enhanced the quality of vision, thus, making the procedure more efficient. No complications have been observed with the use of this device. PMID- 2585631 TI - The use of the flexible ureteroscope in the Stamey urethropexy. AB - Stamey endoscopic suspension of the bladder neck is a reliable technique for treatment of female urinary stress incontinence; however, inadvertent passage of the suture into the bladder lumen must be recognized by the surgeon. The use of a flexible ureteroscope through a suprapubic sheath allows for continuous visualization of the bladder lumen during passage of the needles, and achieves greater control and facility in performing the procedure. PMID- 2585632 TI - Pericatheter retrograde urethrography: introduction of a new device and technique. AB - We describe a new device and technique that allowed for radiographic evaluation of anastomoses before removal of the catheter in 80 patients who had undergone either radical retropubic prostatectomy or urethroplasty. Of these patients 11 showed significant extravasation and required continued catheterization. We advocate this procedure for documentation of complete urethral healing to prevent premature catheter removal. PMID- 2585630 TI - Technique of pudendal nerve localization for block or stimulation. AB - A diagnostic technique is described for study of the pudendal nerve via a dorsal rather than perineal approach. The method offers unique advantages for the urodynamic study of sphincteric function. The patient is placed in the prone position with slight flexion of the hips. The position of the ischial spine is identified topographically using the ischial tuberosities, greater trochanter and lower edge of the ischial-tuberous ligament. Local anesthesia and electrical stimulation then are used to position a needle tip adjacent to the pudendal nerve. This approach allows for specific localization of the nerve for accurate temporary or permanent nerve block. It also permits continuous urodynamic monitoring of pelvic floor behavior with stimulation of the pudendal nerve to assess functional integrity of the nerve and the pelvic floor striated muscles. PMID- 2585633 TI - Prepubic urethrectomy. PMID- 2585634 TI - A simple technique for removal of eroded penile prostheses. AB - Erosion of a penile prosthesis into the urethra is an uncommon complication of implantation. However, such conditions as too large a prosthesis, iatrogenic injury to the urethra at operation, postoperative prosthetic infection and subsequent urethritis may result in this untoward effect. A simple technique for removal of an eroded malleable or self-contained, inflatable or mechanical prosthesis is reported. This procedure is performed without an incision and may be conducted at the bedside with intravenous sedation only. PMID- 2585635 TI - New sterilizing apparatus for flexible cystoscope. AB - A new set-up for sterilization of flexible cystoscopes has been designed that is safe, efficient and practical in a urology office. PMID- 2585636 TI - The outcome of renal transplantation in children with the prune belly syndrome. AB - Children with the prune belly syndrome are at high risk for renal failure. The effect of the prune belly syndrome on the outcome of renal transplantation was evaluated in a retrospective study in which 8 transplant recipients with this syndrome were randomly matched with 13 control, nondiabetic transplant patients. The parameters evaluated were patient and graft survival, renal function and interval until transplantation. The patients were matched by computer for age at transplantation, date of transplantation, immunosuppressive therapy used and type of donor. Data were analyzed by the Gehan test. There was no statistically significant difference in patient deaths (1 versus 3), graft survival (75 versus 69%) or graft function between patients with the prune belly syndrome and controls. Patients with the prune belly syndrome waited a shorter interval for transplantation than did controls (no statistically significant difference) because the distensible abdominal wall characteristic of the syndrome permits placement of an adult kidney in a young child. The prune belly syndrome did not adversely affect the outcome of renal transplantation in these patients. PMID- 2585637 TI - Neonatal bladder rupture: a complication of umbilical artery catheterization. AB - We report on 2 cases of neonatal bladder rupture that resulted from umbilical artery manipulation. This rare complication occurs because of the close proximity of the urachus to the umbilical arteries and peritoneal reflection, and results in urinary ascites and respiratory compromise. Among 11 neonates in the literature who experienced this complication the mortality rate was 18% but all 8 neonates who underwent surgical repair, including our 2 patients, survived. PMID- 2585638 TI - Nephrogenic adenoma of the bladder in children. AB - Nephrogenic adenoma is an uncommon entity, particularly in children. This benign lesion is believed to represent urothelial transformation in response to trauma or inflammation. Current treatment is local resection with fulguration of the base of the lesion, long-term antimicrobial therapy and periodic cystoscopy. Our 2 cases support not only the urothelial transformation theory but raise the possibility that immunosuppression may be a contributing factor in these lesions. PMID- 2585639 TI - Hypertension and renal artery aneurysm: spontaneous cure. AB - An 18-year-old man is described with an aneurysm of the left renal artery diagnosed during study for hypertension. Medical treatment achieved control of the blood pressure. The patient voluntarily interrupted treatment 1 1/2 years after initial diagnosis but the blood pressure remained normal. Angiography at that time revealed almost complete thrombosis of the aneurysm and peripheral plasma renin activity returned to normal in contrast to the high figures registered initially (15 ng. per ml., normal values 0.51 to 2.64). The patient had normal blood pressure, received no medication and was on only a salt-free diet 1 year after this event. PMID- 2585640 TI - Real-time, multiplanar computerized tomography: a new diagnostic modality used in the detection and endoscopic removal of a distal ureteral fibroepithelial polyp and adjacent calculus. AB - Ureteral fibroepithelial polyps are rare benign mesodermal tumors that occur predominantly in the upper ureter. We report on a patient with a fibroepithelial polyp in the distal ureter that resulted in entrapment of a calculus and partial obstruction of the collecting system. Preoperatively, diagnosis by standard radiographic methods, such as excretory urogram, retrograde pyelogram and conventional computerized tomography with and without contrast enhancement, was not possible because of the close proximity of the fibroepithelial polyp, the ureteral calculus and calcifications in the adjacent internal iliac artery. The new diagnostic modality of real-time, multiplanar computerized tomography imaging using the Sun/Pixar computer system and the 2D/3D Orthotool software was used to make the correct preoperative assessment. Subsequently, the patient underwent ureteroscopic resection of the polyp and extraction of the calculus. A year later she was free of symptoms and there was no evidence of regrowth of the polyp. To our knowledge this is the first report to describe the use of real-time, multiplanar computerized tomography imaging as an effective diagnostic modality in the genitourinary tract. In addition, this is the first ureteral fibroepithelial polyp reported in the literature to be associated with a ureteral calculus and to be excised endoscopically with no recurrence on long-term followup. PMID- 2585641 TI - Colchicine therapy in primary amyloidosis of the bladder: a case report. AB - A patient with diffuse localized amyloidosis of the bladder was considered for cystectomy because of intractable gross hematuria. Oral colchicine (2 mg. daily) was commenced and 4 years later the patient was asymptomatic with minimal evidence of amyloidosis cystoscopically. PMID- 2585642 TI - Biodistribution and radioimmunoscintigraphy studies of renal cell carcinoma using tumor-preferential monoclonal antibodies and F(ab')2 fragments. AB - The in vivo localization of renal cell carcinoma-preferential monoclonal antibodies A6H, D5D, and C5H was evaluated and the biodistribution of F(ab')2 antibody fragments of A6H and the intact Mab were compared in over 100 nude mice. A6H localized well to most renal cell carcinoma xenografts studied; the median tumor to blood ratios ranged from 6.4 to 11.5 for various xenografts. C5H also localized well to most renal cell carcinoma xenografts tested. However, D5D did not localize well to renal cell carcinoma xenografts in vivo despite its highly restrictive in vitro reactivity. The F(ab')2 fragments of A6H produced higher tumor to blood ratios, which probably resulted from fast clearance of the fragments from the circulation. Preliminary results showed that indium-111 labeling may further improve imaging. PMID- 2585643 TI - Combined therapeutic effects of conventional agents and an immunomodulator, PSK, on rat prostatic adenocarcinoma. AB - Growth alteration effects of an immunomodulator, PSK, were investigated individually and in association with conventional chemotherapeutic agents cyclophosphamide, cisplatin and fluorouracil in an experimental prostatic cancer model. Copenhagen rats had subcutaneous tumors induced by injections of cells cultured in vitro from a highly metastatic hormonally unresponsive subline of the Dunning rat prostatic tumor, MAT-LyLu. Treatment with conventional agents and the immunomodulator agent individually and in combination began three days after tumor cell inoculation. PSK used alone was not able to significantly influence tumor growth. In appropriate doses, each conventional agent significantly retarded tumor growth. Used in combination, PSK and conventional agents retarded tumor growth locally and decreased metastatic spread of the tumor. Animals receiving combination therapy had increased life spans over those animals receiving single standard chemotherapeutic agents. Immunomodulation with PSK may enhance the antineoplastic effects of chemotherapeutic agents and offer a treatment option for hormone resistant prostatic cancer. PMID- 2585644 TI - Sequential flow cytometry and single gene analysis by enzymatic amplification and allele specific oligonucleotide hybridization of urothelial cells. PMID- 2585645 TI - Bladder function in rats with short- and long-term diabetes; effects of age and muscarinic blockade. AB - The development of alterations in urinary bladder function was studied in rats during six months of streptozotocin-induced diabetes. The results were compared with those obtained in age-matched controls. The bladders from the control rats developed with increasing age an increased micturition volume, a decreased micturition interval, and increased bladder compliance and capacity despite an unaltered bladder weight and unaltered passive and active length-tension relations. The effects of muscarinic blockade were somewhat more pronounced in the older control rats. Following streptozotocin 24 hour diuresis increased rapidly to stabilize within two weeks at a level 15 times higher than the original. This was accomplished initially by an increase in the micturition frequency and then gradually by an increased micturition volume. After six weeks bladder weight had increased more than twofold and did not increase further with time. Despite this both micturition volume and bladder capacity increased from six weeks to six months of diabetes. The diabetic bladders had at low frequencies of stimulation a higher resistance to scopolamine than their age-matched controls. At higher frequencies the resistance to muscarinic blockade showed a similar decrease with age as for the controls. The more pronounced decrease in micturition pressure following atropine treatment in six weeks diabetic rats thus suggests an increased excitation frequency during micturition. No supersensitivity to carbachol was found even after six months of diabetes. PMID- 2585646 TI - The genitourinary spheroidal membrane: an experimental study of a new percutaneously inserted prosthetic device for the control of urinary incontinence. AB - The genitourinary spheroidal membrane, composed of silicone rubber, has been developed along with a mechanical delivery instrument that allows transcutaneous insertion of the prosthetic sphere in the periurethral tissues to enhance outlet resistance in incontinent patients. An experimental study was undertaken in six female mongrel dogs to evaluate the safety and efficacy of this concept. The leak point pressure increased from five to 38 cm. H2O (mean increase, 16.8 cm. H2O). This increase is statistically significant (p less than 0.024, two-sided t test). During the 90-day experiment, there was no migration of the spheres, minimal local inflammatory response, and no granuloma formation or inflammatory response in various organs studied. Although the leak-point pressure was increased in all of the dogs, none developed difficulty voiding. We conclude that the design concept is sound and safe, the delivery system is reliable, and it is possible to place the spheroidal membrane into an anatomic location that will increase outlet resistance. PMID- 2585647 TI - Renal microradiography of experimental ureteral obstruction in the rabbit. AB - Microradiography of nephrons in kidneys perfusion-fixed with glutaraldehyde permits examination of large numbers of nephrons. This technique was applied to rabbits between one and 14 days following unilateral ureteral ligation. Kidneys without ureteral occlusion served as controls. By two days after ureteral obstruction there was dilatation of the ducts of Bellini and papillary collecting ducts. At three to four days there was splaying and tortuosity of the loops of Henle. By eight to 10 days the proximal straight tubules were noted to be dilated and helically twisted. After two weeks of ureteral obstruction there was dilatation of Bowman's space with encroachment on the glomerular capillary tuft. At this time many proximal convoluted tubules began to show atrophic changes. These morphologic alterations may due in part to back pressure on the nephrons, with retrograde progression as the duration of urinary tract obstruction is increased. The distal convoluted tubule and the descending limb of the loop of Henle were not noted to be abnormal during the study. PMID- 2585648 TI - A clinicopathologic study of aneurysm formation of glutaraldehyde-tanned human umbilical vein grafts. AB - To clarify the process of graft degeneration and aneurysm formation we reviewed the angiographic and pathologic findings of three cases where aneurysms developed in glutaraldehyde-tanned human umbilical vein grafts. Seven aneurysms were detected in these three grafts 4 years after implantation. Six aneurysms originated from the bodies of the grafts and one originated from the factory created anastomosis required for fabrication. Wrinkling and segmentation of the dilated graft documented by arteriography corresponded to mural dissection of the graft wall. Large protrusions near the aneurysms were revealed to be the transmurally dissected graft walls. At the site of dissection, blood escaped through the surrounding mesh of the graft to form a preaneurysmal change. Two aneurysms developed without breakdown of the outer mesh. The aneurysm of factory created sutures was caused by tearing of the graft wall. Degeneration of human umbilical vein grafts, which appears to ensue inevitably with the passage of time after implantation, leads to the tear of the graft wall and transmural dissection to form aneurysm. In our department, candidates for human umbilical vein graft implantation have recently been restricted to the patients whose life expectancy is limited to only a few years because of the risk of aneurysm formation. PMID- 2585649 TI - Errors and pitfalls in intraarterial thrombolytic therapy. AB - Sixty complications occurred during 138 courses of intraarterial thrombolytic therapy in 122 patients during a 5-year period. These complications were recorded and analyzed prospectively to identify underlying errors in management. There were 31 bleeding episodes, 15 vascular complications, and 14 other complications. Twelve of the bleeding episodes occurred at the puncture site, and 19 occurred at remote sites, accounting for six of the eight deaths in the series. Management errors were clearly identified in 27 of the 60 complications. The three following patterns of errors were recognized: (1) mismanagement of bleeding (12 instances), (2) wrong patient selection (nine instances), and (3) breach of the administration protocol (six instances). The group of 27 complications with underlying management errors included seven of the eight deaths in the present series. Efforts to prevent complications from thrombolytic therapy should concentrate on the specific patterns of management errors identified. This study indicates that low-dose intraarterial thrombolytic therapy is not a low-risk alternative to surgical intervention but should be viewed as a prelude or possible alternative to surgery in selected patients despite the risks involved. PMID- 2585650 TI - The value of silent myocardial ischemia monitoring in the prediction of perioperative myocardial infarction in patients undergoing peripheral vascular surgery. AB - Real-time electrocardiographic monitoring for silent myocardial ischemia was performed on 200 patients undergoing peripheral vascular surgery to try to better define those at high risk of perioperative myocardial infarction. The patients were divided into those undergoing abdominal aortic aneurysm or lower extremity revascularization procedures (group I, n = 120) and those undergoing carotid artery endarterectomy (group II, n = 80). Silent ischemia was detected during the preoperative, intraoperative, or post-operative periods in 60.8% of group I and 67.5% of group II patients. Six group I and three group II patients suffered an acute perioperative myocardial infarction with two cardiac deaths. In both groups I and II a variety of parameters based on monitoring of silent myocardial ischemia were compared between the subgroups of patients who had myocardial infarction and those who did not. The results show that in both groups there was a significantly (p less than or equal to 0.05) greater total duration of perioperative ischemic time, total number of perioperative ischemic episodes, and total duration of perioperative ischemic time as a percent of total monitoring time in patients who suffered a perioperative myocardial infarction compared to those who did not. Multivariate logistic regression analysis of preoperative characteristics in all 200 patients showed the occurrence of preoperative silent myocardial ischemia and angina at rest to be the only significant predictors of perioperative myocardial infarction. Thus perioperative monitoring for silent myocardial ischemia might noninvasively identify those patients undergoing peripheral vascular surgery who are at increased risk for perioperative myocardial infarction, permitting implementation of timely preventive measures in selected patients. PMID- 2585651 TI - The treatment of thoracic outlet syndrome: a comparison of different operations. AB - Although transaxillary first rib resection is one of the popular treatments for thoracic outlet syndrome today, recurrences and nerve injuries have led to investigation of other operations that might reduce complications and improve results. This article compares the results of transaxillary first rib resection with (1) scalenectomy (anterior and middle) and (2) supraclavicular first rib resection with scalenectomy. Between 1964 and 1987, 668 primary operations were performed for thoracic outlet syndrome on 491 patients. Seventy-one percent were women. Eight-six percent gave histories of neck trauma, often a whiplash injury (traumatic thoracic outlet syndrome); 4.5% had cervical ribs. Common symptoms included paresthesia in the hands (90%); arm pain (80%); neck pain (86%); and occipital headaches (69%). On physical examination, tenderness over the scalene muscles and duplication of symptoms with the arms abducted to 90 degrees in external rotation were present in over 90% of patients. By use of life-table analysis methods, success after surgery was found to be the same for all operations: 91% to 93% at 3 months; 76% to 79% at 1 to 2 years; 70% to 73% at 3 to 5 years; and 69% to 72% at 5 to 10 years. After rib resection plexus injuries occurred in 2.6%, with partial disability in 0.5%. No plexus injuries occurred after scalenectomy, but temporary phrenic nerve palsy occurred in 4.4%. Scalenectomy is as successful an operation as first rib resection for traumatic thoracic outlet syndrome and has fewer serious complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585653 TI - Walking ability and ankle systolic pressures: observations in patients with intermittent claudication in a short-term walking exercise program. AB - Walking ability and limb hemodynamics were studied in 56 patients with intermittent claudication in an exercise program. Patients walked 1 hour 3 times a week for 3 to 6 months. Ankle and brachial pressures were measured at rest and after a standard walk, and walking ability on the treadmill and during free walking was determined. Average maximal distance on the treadmill increased from 0.59 to 1.00 km after training (p less than 0.0001). Also, after training 84% of patients were able to walk continuously more than 2 km without severe discomfort. The attained walking ability of individual patients could not be predicted from pressure measurements. Small pressure changes after training suggested that factors other than increased development of collateral vessels were important in determining walking ability. Practically useful walking ability was achieved in patients with aortoiliac and femoropopliteal arterial obstruction in the presence or absence of coronary disease and in patients taking beta-blockers. The results indicate that walking exercise is a valuable treatment for many patients with claudication who are not candidates for arterial reconstruction. PMID- 2585652 TI - Mycotic aneurysms of the suprarenal abdominal aorta: prolonged survival after in situ aortic and visceral reconstruction. AB - Necrotizing infection of the arterial wall causes rupture and false ("mycotic") aneurysm formation, with a very poor prognosis if untreated. Cure can be achieved by surgical drainage and debridement, with restoration of arterial continuity through uncontaminated tissues. The dilemma of applying these principles to the treatment of mycotic aneurysms of the suprarenal aorta is that no remote or extraanatomic routes are available to maintain perfusion to the viscera. We report the first case of Klebsiella suprarenal mycotic aortic aneurysm successfully treated with in situ prosthetic reconstruction of the aorta and visceral arteries, and we have reviewed the 21 other suprarenal mycotic aortic aneurysms reported in the English-language literature. Repair was performed in 20 of the 22 cases, with in situ prosthetic reconstruction performed in 18. Prolonged survival has been achieved in 16 patients after in situ repair. No long term survival has been reported after extraanatomic reconstruction of the aorta and visceral arteries in patients with such aneurysms. We conclude that in situ prosthetic reconstruction, accompanied by thorough drainage and debridement, prolonged parenteral antibiotic therapy, and permanent suppressive oral antibiotics, offers the best chance for survival in these patients. PMID- 2585655 TI - Long-term follow-up and clinical outcome of carotid restenosis. AB - The efficacy of carotid endarterectomy is dependent on the inherent ability of the operation to prevent stroke as well as the incidence of restenosis and associated symptoms. To examine the long-term effects of restenosis, 301 patients having carotid endarterectomy were followed by serial duplex scanning for an average of 4 years. Carotid restenosis, defined as 50% or greater diameter reduction by duplex scanning, occurred after 78 of the endarterectomies; regression of recurrent stenosis occurred in 20 arteries. By life-table analysis the cumulative incidence of restenosis at 7 years was 31%, and the cumulative incidence of regression was 10%. Thus the prevalence of recurrent stenosis at 7 years was 21%. Restenosis developed in women more frequently than men (p = 0.01). Transient ischemic attack occurred in 12% of patients with restenosis, and stroke occurred in 3%; however, the cumulative incidence of stroke or transient ischemic attack was not statistically different in those patients with and without restenosis. Similarly, cumulative survival at 7 years was no different. Carotid restenosis usually occurs early in the postoperative period and tends to regress or remain stable during long-term follow-up. A conservative approach to treatment appears justified, since transient ischemic attacks and stroke were rarely associated with restenosis. PMID- 2585654 TI - Resting gated pool ejection fraction: a poor predictor of perioperative myocardial infarction in patients undergoing vascular surgery for infrainguinal bypass grafting. AB - Ventricular ejection fraction is widely regarded as a prognostic indicator of perioperative myocardial infarction. To evaluate this premise the prevalence of perioperative myocardial infarction or cardiac death was analyzed in relation to preoperative resting gated pool ejection fraction in 85 patients undergoing vascular surgery for infrainguinal bypass grafting. Patients were divided into three groups on the basis of ejection fraction. Group I consisted of 50 patients with ejection fractions of 56% to 92%. Nine (18%) perioperative myocardial infarctions occurred in group I, and there were no cardiac deaths. Group II consisted of 20 patients with ejection fractions of 37% to 55%. Three (15%) myocardial infarctions occurred in this group, and there were no cardiac deaths. Group III included 15 patients with ejection fractions of 20% to 35%. Three (20%) cardiac events occurred in group III including one nonfatal myocardial infarction and two (13%) cardiac deaths. Statistical analysis showed no significant difference in prevalence of cardiac events between any group. These results suggest that resting ejection fraction is a poor predictor of perioperative myocardial infarction in patients undergoing vascular surgery. Patients with normal ejection fractions, but underlying coronary artery disease, are still at significant risk for a perioperative cardiac event. PMID- 2585656 TI - Guidelines for hospital privileges in vascular surgery. AB - This is a report by an ad hoc committee to the Joint Council of the Society for Vascular Surgery and the International Society for Cardiovascular Surgery (North American Chapter) concerning guidelines that hospitals may use or modify when judging individual applicants for hospital and operating room privileges in vascular surgery. The committee recognizes that the completion of training and obtaining a board certificate is testimony to the qualification but not necessarily the competence of an individual to practice vascular surgery. This report identifies three categories of applicant for privileges in vascular surgery; the surgeon who just completed training, the surgeon who completed training after 1984, and the surgeon who completed training before 1984. In addition, the committee recognizes the importance of periodic vascular surgery privileges renewal for established surgeons. Several pathways are defined for use by hospital privilege committees to evaluate the competence of an individual to be granted privileges in general vascular surgery. The ad hoc committee also has outlined a program for evaluation of established surgeons for renewing privileges in vascular surgery using a mechanism of case outcome audit. Finally, a review mechanism, potential corrective actions, and an appeals mechanism are also suggested. This report represents optimal criteria that may require modification by individual hospitals to meet local community needs and standards. It is the hope of the ad hoc committee that this report will help hospitals and practicing physicians improve the quality of care and treatment outcome in patients with vascular disease. PMID- 2585657 TI - Axillobrachial artery bypass grafting with in situ cephalic vein for axillary artery occlusion: a case report. AB - The cephalic vein has been reported to be a suitable vascular conduit for arterial reconstructive surgery, but its use remains controversial. When used for lower extremity revascularization, its use has been complicated by elongation and dilation. Its use for upper extremity revascularization has only been rarely reported. This article represents the first published use of the cephalic vein with the in situ technique for upper extremity occlusive disease. This technique may avoid some of the complications noted when used in the reverse fashion. PMID- 2585658 TI - Tuberculous aneurysm of the femoral artery: a complication of bacille Calmette Guerin vaccine immunotherapy--a case report. AB - A case of bilateral femoral mycotic aneurysms resulting from bacille Calmette Guerin vaccine, is reported in a 74-year-old man treated by intravesical immunotherapy. The diagnosis was made after histologic and bacteriologic examinations and biochemical analysis of the acid-fast-baccilli. Treatment consisted of resection and replacement of the femoral arteries, with an expanded polytetrafluoroethylene graft on the left side and a saphenous vein graft on the right side. After surgery the patient was treated with antituberculous chemotherapy for 1 year. The patient was doing well 18 months later. PMID- 2585660 TI - Transvenous devices for inferior vena cava interruption. PMID- 2585659 TI - Epithelioid hemangioendothelioma of the external iliac vein: a primary vascular tumor presenting as traumatic venous obstruction. AB - A 32-year-old man employed as a laborer presented with the signs and symptoms of iliofemoral venous obstruction of 1 months' duration. Results of initial phlebography from the ankle to the femoral area were normal. No iliac vein anatomy was seen. This led to a group of tests directed toward neuromuscular function, which were unrewarding. On referral to our institution a noninvasive venous vascular laboratory examination was performed, which clearly indicated iliac vein obstruction/stenosis, with a normally patent distal venous system. Subsequent repeat phlebography, including direct femoral vein injection, visualized a mass lesion partially occluding the iliac vein. This lesion was treated with primary excision and segmental venous replacement with an interposition graft of autogeneous internal jugular vein. The excised lesion proved to be an epithelioid hemangioendothelioma of the iliac vein. PMID- 2585661 TI - Report from the first meeting of the International Society for Applied Cardiovascular Biology. PMID- 2585663 TI - Technology, cost, cooperation, ethics challenges face genome mapping plan. PMID- 2585662 TI - Simpler times. PMID- 2585664 TI - From the Food and Drug Administration. PMID- 2585665 TI - From the Centers for Disease Control. Outbreak of invasive pneumococcal disease in a jail--Texas, 1989. PMID- 2585666 TI - From the Centers for Disease Control. Prevention and control of tuberculosis in correctional institutions: recommendations, advisory committee for elimination of tuberculosis. PMID- 2585667 TI - The doctor as patient advocate. PMID- 2585668 TI - The prevention of deaths from reactions to insect venoms. PMID- 2585669 TI - Dyslexia. PMID- 2585670 TI - Rhabdomyolysis in fatal arsenic trioxide poisoning. PMID- 2585672 TI - Autologous fibrin for blepharoplasty incisions. PMID- 2585671 TI - School-based clinics' birth, fertility, and abortion rates. PMID- 2585673 TI - Medical malpractice experience of physicians. Predictable or haphazard? AB - This study uses a large malpractice database from Florida to assess the concentration of losses among physicians, predictability of claims experience, characteristics of physicians with favorable vs unfavorable experience, and effects of claims experience on physicians' practice decisions and on actions taken by the state's licensing board. Most payments by insurers involved a comparatively small number of physicians. Physicians with relatively prestigious credentials had no better, and on some indicators, worse claims experience. If anything, physicians with adverse claims experience were less likely to make subsequent changes in their practice, such as quitting practice or moving to another state. Physicians with very poor claims histories were more likely to have complaints filed against them with the Florida licensing board, but the sanctions against physicians with either poor or excellent histories were not severe. Physicians with adverse claims experience from incidents that arose between 1975 and 1980 had appreciably worse claims experience from incidents that arose during 1981 to 1983. PMID- 2585675 TI - Factors associated with the recommendation for endocarditis prophylaxis in mitral value prolapse. AB - We conducted a population-based study to examine the association between clinical and Doppler echocardiographic characteristics and physicians' recommendation for endocarditis prophylaxis. Of 127 consecutive Olmsted County, Minnesota, residents with newly documented isolated mitral valve prolapse, endocarditis prophylaxis was recommended three to four times more often in patients under 40 years compared with those more than 60 years of age. Using multiple logistic regression, for every 10-year increment in age, there was a 30% independent reduction in recommendations for endocarditis prophylaxis. Doppler evidence of mitral regurgitation was also independently associated with recommendations for endocarditis prophylaxis. Observations from physical examination, including systolic murmur and systolic click, were weakly associated with endocarditis prophylaxis recommendations. Mitral valve appearance (thickened vs not) was not associated with endocarditis prophylaxis. Although current recommendations for endocarditis prophylaxis and mitral valve prolapse do not address age and Doppler detected mitral regurgitation, these variables are strongly associated with clinical decisions. Prospective, longitudinal, population-based studies are needed to define endocarditis risk further in subgroups with mitral valve prolapse to provide a more scientific basis for clinical decision making. PMID- 2585674 TI - Detection of depressive disorder for patients receiving prepaid or fee-for service care. Results from the Medical Outcomes Study. AB - We estimated clinicians' awareness of depression for patients with current depressive disorder (N = 650) who received care in either a single-specialty solo or small group practice, a large multispecialty group practice, or a health maintenance organization in three US sites. Depressive disorder was determined by independent diagnostic assessment shortly after an office visit. Detection and treatment of depression were determined from visit-report forms completed by the treating clinician. Depending on the setting, from 78.2% to 86.9% of depressed patients who visited mental health specialists had their depression detected at the time of the visit, compared with 45.9% to 51.2% of depressed patients who visited medical clinicians, after adjusting for case-mix differences. Among patients of mental health specialists, there were no significant differences by type of payment in the likelihood of depressive disorder being detected or treated. Among patients of medical clinicians, however, those receiving care financed by prepayment were significantly less likely to have their depression detected or treated during the visit than were similar patients receiving fee-for service care. PMID- 2585676 TI - Active euthanasia in The Netherlands. AB - Active euthanasia in the Netherlands remains a topic for both professional and public debate. However, many aspects of the medical practice of active euthanasia remain unclear, and no figures on the actual incidence of this practice exist. Legally, active euthanasia is a criminal offense, but a pattern of jurisprudence has developed since the first court case in 1973 that has allowed physicians to practice euthanasia under certain strict conditions. Two proposals, one from the Royal Dutch Medical Association and one from a government-appointed state commission, have advised that the current law be changed. While the debate continues, a number of Dutch institutions have developed procedures and policies to enable physicians and health care providers to participate in active euthanasia in an acceptable and controllable manner. However, many Dutch physicians remain uncomfortable with the professional and public tolerance of this practice. PMID- 2585677 TI - Medical malpractice and the tort system. PMID- 2585678 TI - Determination of gestational cocaine exposure by hair analysis. AB - Drug self-reports are often unreliable and standard blood and urine tests detect only recent cocaine use. Since cocaine is deposited in hair, we have applied a radioimmunoassay to hair extract to detect past cocaine use. Hair from 16 adult users was positive for benzoylecgonine, in the presence of negative findings from urine screening tests. Benzoylecgonine in admitted heavy users averaged 8775 ng/g of hair (range, 640 to 29,089 ng/g of hair), whereas in occasional users it averaged 624 ng/g of hair (range, 32 to 1210 ng/g of hair). Benzoylecgonine was not detected in hair of 21 adults who reported no use of cocaine ever and whose urine samples were negative for the metabolite. Neonatal hair from seven infants whose mothers were known cocaine users averaged 5430 ng of benzoylecgonine per gram of hair (range, 200 to 27500 ng/g of hair). Hair from two infants 2.5 and 3.5 months of age averaged 6050 ng of benzoylecgonine per gram of hair. However, values were negative for infants 1 year and older, corresponding to loss of fetal hair in the few months after birth. Because studies reporting reproductive risks of cocaine compare exposed and nonexposed groups, validation of drug-free status of control subjects is extremely important. Hair analysis may remedy the disadvantages of currently used methods and may identify intrauterine exposure to cocaine in babies when a maternal drug history is not available or of doubtful truthfulness. PMID- 2585679 TI - Drug screening in an unconventional matrix: hair analysis. PMID- 2585680 TI - A piece of my mind. The generic H & P. PMID- 2585681 TI - Health and safety standards being developed for child-care programs. PMID- 2585682 TI - 'HeartGuide' food-rating program attracts 114 applications as controversy continues. PMID- 2585683 TI - From the Congressional Office of Technology Assessment. PMID- 2585684 TI - Prison rape and suicide. PMID- 2585685 TI - Radon and smoking status. PMID- 2585686 TI - Counseling about physical activity. PMID- 2585687 TI - A piece of my mind. Long ago today. PMID- 2585688 TI - Reporting the results of human immunodeficiency virus testing. AB - We conducted a pilot study of potential sources of incorrect laboratory reports of human immunodeficiency virus type 1 testing using blind proficiency testing. Sets of three serum samples, including one serum sample with negative reactions in antibody tests, one serum sample with positive reactions, and one that gave false-positive results with certain testing kits, were sent as routine patient specimens to testing laboratories. Half the laboratories reported the serum sample positive for human immunodeficiency virus antibodies as "indeterminate"; one laboratory rendered a final positive report without supplemental testing. On the report forms, the actual laboratory results were often obscured and intermingled with information, sometimes incorrect, such as identifying the agent as "HTLV-III" (human T-cell lymphotropic virus type III) and advising that a test with positive results is evidence of exposure to the virus. Many of these reports have the potential to confuse, rather than to enlighten, the requesting physician. PMID- 2585689 TI - Application of clinical indicators in the emergency department. AB - Clinical indicators were developed and used to assess the quality of patient care resulting from the system of shared responsibility between emergency department (ED) and radiology department faculty physicians for interpretation of ED roentgenograms. The first indicator--all discrepancies in roentgenogram interpretation between ED and radiology department faculty--measured an overall discrepancy rate of 3.3% (776 films). Three hundred fifty-two apparent discrepancies were not related to the accuracy with which ED faculty interpreted films, resulting in a revised overall discrepancy rate of 1.8%. The second indicator--undesirable patient care outcomes as a result of delayed accurate radiological diagnosis--measured an occurrence rate of 0 after clinical reevaluation of more than 99% of patients within 24 hours of initial ED evaluation. Aspects of the development and use of clinical indicators are discussed in relationship to the broader monitoring and evaluating process necessary for the continuous improvement of patient care. PMID- 2585690 TI - Doctors, drug companies, and gifts. AB - Doctors often accept gifts from drug companies. We analyze this practice and conclude that accepting a gift has complex practical and ethical repercussions. Gifts cost patients money, and they may change society's perception of the profession as serving the best interest of patients. Also, accepting a gift establishes a relationship between the physician and the drug company that obliges a response from the physician. Accepting gifts and the resulting relationship have ethical implications as well. First, the use of patients' money to pay for gifts can be unjust. Second, the fiduciary relationship between physician and patient may be threatened if prescribing practices are affected (as intended by the drug company). Third, physicians' characters may be altered by a practice that fosters self-interest at patients' expense. We discuss the need for guidelines for the profession to help physicians promote their patients' well being. PMID- 2585691 TI - Markers for transfusion-transmitted disease in different groups of blood donors. PMID- 2585693 TI - Proceedings of the 53d annual scientific meeting of the Japanese Circulation Society. March 1989, Nagoya. Abstracts. PMID- 2585692 TI - Are human immunodeficiency virus test reports clear to clinicians? PMID- 2585694 TI - [Response of the cervical sympathetic activity to acute hypoxemia in dogs and its modification by volatile anesthetics]. AB - Response of the cervical sympathetic activity (CSA) to acute hypoxemia was studied in dogs in the absence and in the presence of either halothane (H), enflurane (E), isoflurane (I) or sevoflurane (S). Multifiber potentials of CSA, EEG, heart rate (HR), arterial blood pressure (ABP) and arterial oxygen saturation (SaO2) were continuously monitored. CSA increased responding to acutely induced hypoxemia at a speed of -6 - 9% (SaO2).min-1. The response of CSA was estimated in two ways as a function of SaO2: The threshold was determined at the SaO2 level where CSA increased by 3% over the basal level and the gain was determined by the slope of CSA increase divided by the SaO2 span. They were 92% and -1.88 in the absence of volatile anesthetics, respectively. The threshold and the gain decreased markedly in the presence of various concentrations of volatile anesthetics. They were 89.2% and -1.16; 81% and -0.74; 84.2% and -1.16 and 86.2% and -0.94 with 1 MAC of H, E, I and S, respectively. The depressant effects of volatile anesthetics on the CSA responses to acutely induced hypoxemia can cause depressed control of the autonomic nervous system against hypoxemia and conceal the manifestation of clinical signs of hypoxemia. PMID- 2585696 TI - [Power spectral analysis of heart rate and peripheral blood flow variations during total spinal anesthesia]. AB - We evaluated the effect of total spinal anesthesia (TSA) on the heart rate and peripheral blood flow variations to evaluate if TSA could influence these parameters as indicators of autonomic nervous function (ANF). Four patients with intractable pain were treated by TSA by administration of local anesthetics (lidocaine or mepivacaine) into the C7-Th1 vertebral interspace. Power spectrum of heart rate before TSA showed three peaks; low (LO-FR, 0.04-0.095 Hz), mid (MID FR, 0.095-0.15Hz) and high frequency areas (HI-FR, 0.15-0.3Hz). Spectral peaks of LO-FR and MID-FR disappeared during TSA (P less than 0.001). HI-FR area decreased to 3.3% of the control level (P less than 0.001). Mean peripheral blood flow was changed to 59.9% of the control level (not significant). However, peripheral blood flow variations of LO-FR decreased to 11.3% of the control level (P less than 0.001) after TSA. Furthermore, the vagal discharge disappeared promptly after TSA in dog. These results suggest that TSA depresses the vagal activity as well as the sympathetic activity innervating the cardiovascular system and therefore, heart rate and peripheral blood flow variations are totally eliminated. Thus, we conclude that heart rate and peripheral blood flow variations can serve as valid markers of ANF activity. PMID- 2585695 TI - [The effects of nicardipine on morphological changes and calcium accumulation during ischemic hypoxia in pyramidal nerve cells in the rat cerebral cortex]. AB - The morphological changes and the calcium accumulation were studied in the rat pyramidal nerve cells which had undergone 5% oxygen inhalation and bilateral carotid artery clamping for 15 minutes, using combined methods of electron and the X-ray microanalytical microscopes. To study the protective effects of nicardipine on brain hypoxia, the same techniques were also used after the inhalation. In the 5% oxygen inhalation group, the chromatin clamping in the nucleus was observed, but calcium ions could not be detected in the neuron using the X-ray microanalytical techniques. In the carotid clamping groups under 5% oxygen inhalation, severe nuclear change and mitochondrial swelling were observed and calcium ions were detected in the mitochondrion. After administrations of nicardipine under 5% oxygen inhalation and under carotid clamping with 5% oxygen, similar morphological changes were recognized by the electron microscope as compared to the non-administration groups. The rate of calcium ion detection was not different significantly (P less than 0.05) between the nicardipine administration and the non-administration groups. It is, therefore, concluded that notable protective effects of nicardipine on ischemic hypoxia were not recognized in this experiment. PMID- 2585697 TI - [Effects of fentanyl on left ventricular diastolic function]. AB - Effects of fentanyl on left ventricular diastolic function were investigated in chronically instrumented dogs. An electromagnetic mitral flow probe was placed in the left atrium and a micromanometer was placed in the left atrium as well as in the left ventricle to measure ventricular pressure (LVP), left atrial pressure (LAP), derivative of left ventricular pressure (dp/dt), mitral flow (MIF) and ECG in conscious resting dogs. Following induction of anesthesia with thiopental (15 20 mg.kg-1) and vecuronium (0.1 mg.kg-1), fentanyl (10, 50 and 100 mcg.kg-1) was administered at 30 min intervals. The direct measurement of phasic MIF was used to obtain a set of diastolic indices: peak rapid filling period (PRFR), filling volume (FV), FV due to atrial contraction (FV-A), isovolumic relaxation period (IVRP) and diastolic filling period (DFP). Each diastolic index during conscious resting state was compared with that obtained during fentanyl anesthesia using paired t-test. There were no significant changes in those diastolic indices under fentanyl (10, 50 and 100 mcg.kg-1) anesthesia except PRFR and dp/dt under fentanyl 10 mcg.kg-1 which decreased. Although heart rate decreased about 50% under fentanyl, IVRP and PRFR did not increase significantly, but DFP (P less than 0.05) and FV (P less than 0.01) increased significantly. DFP correlated well with RR interval under conscious resting state under fentanyl anesthesia (r = 0.992 and r = 0.967). This study suggests that in the absence of surgical stress, fentanyl does not impair left ventricular diastolic function. PMID- 2585698 TI - [Respiratory effects of epidural anesthesia and anesthetic level obtained in patients for cesarean section]. AB - In order to determine the optimal level of epidural anesthesia, the author examined respiratory function of 138 full-term pregnant women in sitting and supine positions without anesthesia, and in supine position under epidural anesthesia prior to the cesarean section. Vital capacity (VC) increased in the sitting position in comparison with supine position because expiratory reserve volume (ERV) and tidal volume (TV) increased. In contrast, %FFV1.0, peak expiratory flow (PEF) and V75 decreased as uterus shifted anteriorly in the sitting position. Under the epidural anesthesia with T4-T6 analgesic, TV showed a relative increase resulting in an increase in VC. This was due to lateral displacement of the uterus alleviating the depression of diaphragm. Epidural anesthesia with levels C8-T3 caused a reduction in inspiratory reserve volume (IRV) and ERV which in turn resulted in a decrease in VC and PaCO2. This change depended on the paralysis of respiratory muscles and the dyspneic feeling of patient. Generally %FFV1.0 and the data related to flow volume curve decreased under epidural anesthesia. In conclusion, epidural anesthesia with T4-T6 levels accompanied a sufficient analgesic efficacy and respiratory function comparable with that in the sitting position without anesthesia, therefore this was considered to be a method of choice for cesarean section. PMID- 2585700 TI - [Impaired B lymphocyte function during open heart surgery]. AB - Sequential in vitro lymphocyte function tests in 13 patients undergoing cardiac operation were performed to study B lymphocyte function following operation. Lymphocytes were stimulated with phytohemagglutinin (PHA), pokeweed mitogen (PWM) and Staphylococcus aureus Cowan 1 (SAC). Mitogen responses were measured by 3H labeled thymidine incorporation. The SAC responses were significantly depressed following operation. Immunoglobulin secreting cells were measured by protein A plaque forming cell assay. The numbers of immunoglobulin secreting cells induced by PWM or SAC decreased remarkably at least as long as 3 day after the operation. The percentage of circulating B lymphocytes increased significantly postoperatively. This indicates that the B lymphocytes remaining after the operation were functionally impaired. PMID- 2585699 TI - [Thermal analgesia following intrathecal capsaicin administration in rats- detailed measurements of thermal analgesia over the lower body by a thermal probe]. AB - This study was undertaken to examine the thermal pain thresholds over a wide area of the lower body surface following the intrathecal administration of capsaicin in rats. Thermal nociceptive thresholds measured under light halothane anesthesia were determined as skin twitch or escape response latencies to the heat stimulation (52.0 degrees C) by a thermal probe. Capsaicin (50 micrograms in 10 microliters) was injected through a chronically implanted catheter whose tip was near the lumbar enlargement of the spinal cord. The hot-plate test (52.0 degrees C) was also performed in all rats tested. Increase in thermal pain thresholds were consistently observed in the low back and abdominal region, while the hind paws did not always respond with prolonged skin twitch or escape latencies. Intensities of thermal analgesia at the sole of hind paws measured by hot-plate test correlated well with those by thermal probe test. In conclusion, intrathecal capsaicin definitely produced thermal analgesia, but its intensity was considerably variable in the hind paws. These results are in keeping with our previous finding that there was much variability in the effect of capsaicin assessed by the hot-plate test, indicating a possibility that capsaicin does not spread uniformly in the CSF because of its water insolubility or difficulty in penetrating to the large nerve roots innervating the hind paws. PMID- 2585701 TI - [Effect of urinastatin on immunity during anesthesia and surgery for malignant disease]. AB - The effect of urinastatin (Miraclid) on the changes of peripheral lymphocyte subpopulations during the operation for malignancy was investigated. Ten urinastatin-treated patients and twelve non-treated patients undergoing surgery for gastric cancer under general anesthesia were studied. Peripheral lymphocyte subpopulations were measured before and during operation employing two color analysis utilizing two kinds of monoclonal antibody, such as Leu3a and Leu8, Leu2a and Leu15, or Leu4 and HLA-DR. With this analysis, it was possible to classify peripheral lymphocytes into helper T cells, inducer T cells, cytotoxic T cells. suppressor T cells and B cells. Decrease in inducer T cells, increase in suppressor T cells and decrease in B cells were observed in the non-urinastatin treated group during the operation. Furthermore, decrease in OKT4/OKT8 (Leu3a/Leu2a) ratio was demonstrated. But these changes were inhibited in the urinastatin-treated group. This result suggests that the administration of urinastatin improves immunosuppressive state during operation. PMID- 2585702 TI - [Let's study pharmacokinetics related to anesthesiology by using computer graphics: intravenous drugs]. AB - The pharmacokinetics of intravenous drugs used during anesthesia provides us important information for patients' care. The pharmacokinetic data are usually shown in a graphic expression together with numerical values. The numerical values are only convenient for investigators in exchanging their knowledge and information. The graphic data contain, however, whole and real information obtained in a pharmacokinetic study. The authors demonstrated a way to derive information from graphic data, which is practically applicable for patients' care. We also showed a way to calculate numerical values from graphic data by using "graphnote" by Fukutake Pub. Co. We believe that our manual way to calculate numerical values from graphic data, with an aid of computer graphics combined with scientific calculator, helps us to understand the invisible processes performed inside "a black box" or a computer installed with a commercially available soft ware for the pharmacokinetics. PMID- 2585703 TI - [Anesthetic experience in emergency abdominal surgery in a 97-year-old patient complicated with a giant abdominal aneurysm]. AB - We administered general anesthesia for an emergency abdominal surgery due to duodenal ulcer hemorrhage. The patient was in postoperative state after femoral supracondylar fracture, in pre-shock state, of old age (97 y-o), with severe anemia, and hypoproteinemia, and complicated with a giant abdominal aneurysm and mild aortic regurgitation. Before the operation, the patient was transferred to ICU and had intravascular volume replaced (infused with blood 600 ml, crystalloid fluid 2000 ml, colloid fluid 500 ml) and received stomach lavage. Under monitoring of direct arterial pressure, after fully pre-oxygenation, fentanyl 0.1mg was administered slowly, and crush induction was performed by a small dose of thiopental and SCC. After induction of anesthesia systolic blood pressure decreased to 60 mmHg temporarily and it was maintained between 80 and 120 mmHg during the surgery, but tachycardia continued (90-110.min-1). In order to treat oliguria owing to pre-shock state, we administered dopamine and urinastatin continuously. The patient was transferred to ICU postoperatively and close attention was paid. Postoperative pain controlled was well by epidural morphine and bupivacaine. The postoperative course was uneventful without any complications. Twenty three days later, abdominal aortic aneurysm resection was performed uneventfully. In this paper, problems of preanesthetic and anesthetic management of emergency abdominal surgery for an aged patient were discussed. PMID- 2585705 TI - [Cardiac arrest due to lidocaine]. AB - A 65-year-old woman with height of 156 cm and weight of 54 kg, who had previously been healthy, was scheduled for resection of axillary abscess. She was not premedicated. After local infiltration of 1%-lidocaine 25 ml, operation was started under electrocardiographic monitoring. Blood pressure was 190/100 mmHg, heart rate being 80 bpm and EKG showed sinus rhythm. During next 25 minutes, 60 ml of 1%-lidocaine was used because of inadequate pain relief. Two minutes after the last injection of 1%-lidocaine 10 ml, the patient developed significant bradycardia followed by cardiac standstill. Resuscitation was started immediately. Within two minutes, EKG showed idioventricular rhythm followed by junctional escaped rhythm and then sinus rhythm at a rate of 42 bpm appeared. Bradycardia below 50 bpm continued for 9 minutes despite of intravenous administration of atropine. After the recovery of heart beat, the patient became responsive, alert, and oriented, and neither arrhythmia nor ST-T change was observed. Laboratory data showed no abnormality which might have predisposed her to the development of cardiac arrest. Because the cardiac arrest occurred soon after lidocaine injection and no drug other than lidocaine had been used, lidocaine was thought to be the cause of the cardiac arrest. PMID- 2585704 TI - [Anesthetic management in surgery of thoracic aortic aneurysms--a report of eleven cases]. AB - Anesthetic management of patients with thoracic aneurysm is discussed. During a period of two years, 11 cases were observed; 7 cases of dissecting aneurysm and 4 cases of true aneurysm. Dissecting aneurysms were of DeBakey's type 1 in 5 cases and of DeBakey's type 2 in 2 cases. Four cases had hypertension. As many of these patients often have hypertension, it is important not to change the circulatory dynamics during induction of anesthesia. We employed high dose fentanyl in 9 cases and used nitroglycerin or nitroprusside to control systolic blood pressure at about 100-120 mmHg. Massive bleeding can occur during intraoperative period and it is important to secure a sufficient number of intravenous routes to protect the central nervous system during cardio-pulmonary bypass. PMID- 2585706 TI - [Coronary artery spasm under thoracic epidural anesthesia]. AB - Three paroxysmal episodes of ST-segment elevation in lead II of ECG were observed during bullectomy and chest closing under epidural anesthesia supplemented with enflurane in compressed air in a patient who had history of variant angina with 50% obstruction of right coronary artery. The first and the third episodes were followed by ventricular tachycardia, complete A-V block and hypotension. These attacks were preceded by decreases in heart rate and blood pressure. It was suspected that coronary artery spasm developed with increased vagal tone under thoracic epidural block. The first and the second attacks were successfully treated with intravenous injection of nitroglycerin and lidocaine. The third attack needed additional treatments which included intravenous administrations of atropine, epinephrine, isoproterenol and phenylephrine and direct heart massage through the thoracic incision. Postoperative serial examinations of ECG showed inverted T in lead V1-V4, and serum enzymes (GOT, GPT, LDH, CPK, CPK-MB) were elevated. However ratio of CPK-MB to total CPK was only 1.5%. The patient was discharged two weeks after the operation with normal ECG and serum enzymes. It is speculated that coronary artery spasm was induced by hypotension and vagal stimulation under epidural anesthesia which blocks cardiac sympathetic nerves. PMID- 2585708 TI - [Laryngeal mask--a newly designed oral airway]. AB - A newly developed oral airway, laryngeal mask (LM), was used in 40 patients by anesthesiologists of varied clinical experiences. Clear airway was obtained in 37 patients (92.5%). There were 3 patients in whom it was difficult to establish clear airway, probably because of inappropriate fitting of mask to larynx or of folding of epiglottis. Controlled or assisted ventilation was performed adequately in most of the patients, but there was recognizable gas leak in 13 patients when the airway pressure was above 15 cmH2O. The LM has many attractive features compared with a traditional face mask, and some of the promising clinical applications of LM are discussed. PMID- 2585707 TI - [A newly devised continuous catheter flush system for arterial pressure monitoring]. AB - Since Gardner et al. demonstrated a useful continuous catheter flush system in 1970, various systems for blood pressure monitoring have been commercialized. However, some problems have not been solved yet, such as hazard of embolism, infarction, unexpected infusion of large amount of fluid etc.. We have introduced a new type of flush system. which consists of disposable plastic unit with a one way valve newly developed by us (SAT-route) and a syringe pump (Terumo STC-521). Using this system, only 0.5 ml.hr-1 infusion of heparinized saline was sufficient to prevent the formation of thrombus. Flushing was easily achieved by only pushing the purge button of the pump. As a result, simple, safe and high fidelity pressure monitoring was achieved without much altering the waveform of arterial pressure during flushing. The dynamic frequency response obtained from a square wave test was excellent, with natural frequency of about 40 Hz and damping coefficient of about 0.3. This system is useful especially for perioperative management of small children undergoing cardiac surgery, who require an exquisite infusion therapy and fluid restriction. PMID- 2585709 TI - [Effects of inhalation anesthetics on hepatic ATP and L/P ratio in the rat subjected to hemorrhagic shock]. AB - Both anesthetics and hemorrhage may affect the hepatic energy metabolism. The effects of inhalation anesthetics (halothane, enflurane and isoflurane) on hepatic ATP level and L/P ratio were evaluated in rat under hemorrhagic shock. There was no significant difference in the hepatic ATP levels among 4 groups. However the L/P ratio in 3 inhalation anesthetic groups was significantly lower than that in control group. These results suggest that inhalation anesthetics may improve the hepatic energy metabolism during hemorrhagic shock. PMID- 2585710 TI - [Respiratory and circulatory changes after the intratracheal infusion of bile acids in dogs]. AB - We studied the effect of intratracheally infused bile acids on the respiratory and circulatory systems in anesthetized dogs. The bile acids used were cholic acid, deoxycholic acid, taurocholic acid, glycocholic acid and taurodeoxycholic acid. They were diluted to 1% or 10% with normal saline solution and 1 ml.kg-1 was infused into the trachea through an endotracheal tube under a controlled ventilation with air. Injection of 10% diluted bile acid, except for glycocholic acid, decreased PaO2 to less than 50 torr after 15 minutes and increased PaCO2 to above 60 torr after 2 hours. A butterfly shadow appeared in chest radiographs after 1 hour. Microscopic examinations revealed severe pulmonary edema and hemorrhage but circulatory depression was negligible. Hypoxia and hypercapnea were also observed in the 1% dilution group but to a smaller degree. Intrapulmonary water volume increased following injection of bile acid. Our results demonstrated that bile acids induce pulmonary damage. PMID- 2585711 TI - [Changes in canine conjunctival and cerebral oxygen tension during hemorrhagic hypotension]. AB - On-line conjunctival oxygen tension (PcjO2) and cerebral cortical oxygen tension (PcxO2) were measured simultaneously using polarographic oxygen sensors during hemorrhagic hypotension in dogs. Mean arterial pressure (MAP) decreased from a control value of 119 +/- 7 to 52 +/- 1 (SEM) mmHg during initial bleeding of 30 minutes, and then this level of MAP was maintained for another 150min by adjusting the height of the reservoir. During the early phase of arterial hypotension, PcjO2 fell sharply, and this was accompanied by a parallel decrease of carotid artery blood flow and cardiac output, whereas PcxO2 remained unaffected with this level of hypovolemic hypotension which was possibly due to the cerebral tissue autoregulatory mechanism. Thus, it was demonstrated that despite the anatomical similarity and proximity of their blood supply, the conjunctival tissue responded differently to the intracranial cerebral tissues when compared during hemorrhagic hypotension. The study also suggests that monitoring the PcjO2 during surgery may be a useful monitoring tool in detecting early signs of tissue ischemia and hypoxia during hypovolemic shock. PMID- 2585712 TI - [A comparative study of the depressive effects of halothane and isoflurane on medullary respiratory neurons in cats]. AB - The depressive effects of halothane (H) and isoflurane (I) on the same respiratory neuron were studied in cats. Using a tungsten microelectrode, activities of medullary inspiratory neurons were recorded around nucleus ambiguus. The number of spikes (Spike) of each respiratory cycle and inter-spike interval (ISI) were measured. At 1 MAC, in 9 units out of 11, Spike was significantly fewer with I than with H. In 2 units out of 11, Spike was not significantly different between H and I. These results indicate that each respiratory neuron shows different sensitivity to H and I at 1MAC concentration. With increasing depth of anesthesia, Spike showed a concentration-related depression. During the course of respiratory depression, the spikes were 75.9 (1MAC), 63.3 (1.5MAC), 48.0 (2MAC), 24.2 (2.5MAC), 5.0 (3MAC) with H, and 77.4 (0.5MAC), 51.9 (1MAC), 23.5 (1.5MAC) with I. These spikes were completely depressed at 3.5MAC in H and 2MAC in I. Both H and I increased ISI with increasing depth of anesthesia. The effects of H and I on the phrenic nerve discharges closely resembled their effects on the respiratory neurons. We conclude that the respiratory depression produced by I exceeds that produced by equal MAC of H. PMID- 2585713 TI - [Changes in the electroretinogram during enflurane anesthesia]. AB - We have investigated a method of intraoperative monitoring of anesthetic depth using the electroretinogram (ERG). The effects of enflurane on ERG were studied in 12 patients undergoing surgical procedures. Recordings were made at 0%, 0.8%, 1.7% end-tidal enflurane concentrations. There were statistically significant increases in the latencies of the a-waves, b-waves and oscillatory potentials (OP) with increasing concentrations of enflurane. The amplitudes of the a-waves were reduced with increasing concentrations of enflurane, but the amplitudes of the b-waves did not change. The latencies of OP were thought to be the most sensitive indicator of the anesthetic depth among these parameters. To apply this technique to clinical practice, there were many problems to be solved. However, this may be one of useful monitors of anesthetic depth in future. PMID- 2585714 TI - [Effects of sevoflurane anesthesia and surgery on plasma catecholamine levels]. AB - Effects of sevoflurane-nitrous oxide-oxygen anesthesia and surgery on plasma levels of epinephrine, norepinephrine and dopamine were evaluated in twenty four patients who ranged in ages from 15 to 65 years. They underwent non-abdominal surgery (orthopedic surgery) or abdominal surgery (gastrointestinal or gynecological surgery). Anesthesia was induced and maintained with sevoflurane in 50% nitrous oxide and 50% oxygen. Succinylcholine was administered intravenously to facilitate tracheal intubation and pancuronium was given intravenously during surgery. Lactated Ringer's solution at a speed of 5-15 ml.kg-1.h-1 was also administered intravenously throughout the procedures. Neither plasma epinephrine, norepinephrine nor dopamine levels changed significantly during the anesthetic induction with sevoflurane anesthesia. Plasma catecholamines were unchanged during and after surgery in patients who underwent non-abdominal surgery, while plasma epinephrine and norepinephrine levels increased significantly during and after abdominal surgery. Plasma dopamine levels, however, were unchanged during and after surgery in these patients. The findings suggest that epinephrine and norepinephrine secretion was significantly stimulated with abdominal intervention but not with orthopedic one under sevoflurane anesthesia. PMID- 2585715 TI - [The role of catecholamine content in human platelets; clinical implications in patients with pheochromocytoma]. AB - This study examined if the platelet catecholamine content (CA) in healthy adults and patients with adrenal tumors reflected the activity of the sympatho adrenomedullary system. RESULTS: (1) In 44 healthy adults, platelet norepinephrine (NE) levels ranged from 72 to 1175 pg.mg-1.protein-1 (mean: 473pg.mg-1.protein-1) and platelet epinephrine (E) levels ranged from 23 to 273 pg.mg-1.protein-1 (mean: 68 pg.mg-1.protein-1). These were used as normal ranges for this study. (2) In patients with adrenal tumors, plasma CA level, urinary CA elimination and platelet CA content were higher in patients with pheochromocytoma than in those with other adrenal tumors. Mean platelet NE and E levels for patients with pheochromocytoma were 2188 and 336 pg.mg-1.protein-1, respectively. These results indicate that a large amount of CA is contained in platelets (particularly in patients with pheochromocytoma), and that platelet CA level is very useful for preoperative diagnosis of pheochromocytoma. The results also suggest that platelet CA level closely reflects the activity of the sympatho adrenomedullary system. PMID- 2585717 TI - [Spinal anesthesia of only one lower extremity with hypobaric tetracaine]. AB - For spinal anesthesia of only one lower extremity, effect factors, assumed to influence the level of anesthesia including the degree of head-down position of the patients during injection, the volume of the drug and the rate of its injection, are studied using 0.2% hypobaric tetracaine solution in water. Seventy two patients having the surgery of one lower extremity were divided into 7 groups according to the difference in the degree of head-down position (0, 2 and 5 degrees), in the volume (3, 5 and 7 ml) and the rate (0.2, 0.1 and 0.05 ml.s-1) of injection of tetracaine solution. Patients, in lateral position with the operative side up during injection and 20 minutes after injection, were checked for the level of hypesthesia and analgesia on both operative side and non operative side. Except 2 groups of the patients who were in horizontal position during injection or who are injected with 7 ml of tetracaine solution all at once, the upper level of analgesia in the operative side is well controlled at T10, although in some patients the additional injection of small amount of tetracaine solution was needed. In these patients, the analgesic level in the non operative side is restricted within S level, and HR and BP changes were very slight. The rate of injection had no effect on the analgesic level on both operative side and non-operative side. PMID- 2585716 TI - [Hemodynamic changes before and after anesthesia for renal transplantation]. AB - Renal transplantation has come into use as a treatment for renal insufficiency, but infusion management before and after anesthesia for this operation is important. In order to prevent acute necrosis of the uriniferous tubules and to obtain urine outflow in early postoperative stage, a recent practice has been to give rapid infusions of large amounts of fluid, starting during the anastomosis of the renal vessels. We gave a large amount of intraoperative fluid to six patients undergoing transplantation of cadaver kidneys. A Swan-Ganz catheter was inserted into the pulmonary artery and infusion management was performed so as to maintain the pulmonary arterial pressure above 15 mmHg and the pulmonary capillary wedge pressure above 10 mmHg. The cardiac output increased as a result, and no pulmonary edema was seen. We believe that our method of infusion management using a Swan-Ganz catheter is a useful technique in such cases. PMID- 2585718 TI - [Effect of high-frequency oscillation on hypoxic pulmonary vasoconstriction]. AB - We studied the effect of high-frequency oscillatory ventilation (HFO) on hypoxic pulmonary vasoconstriction (HPV) in mongrel dogs. Arterial blood gas as well as pulmonary and systemic hemodynamic variables were measured. Using a double-lumen endotracheal catheter, the right lung was ventilated by controlled mechanical ventilation (CMV) and the left lung was ventilated by CMV (controlled group, n = 5), HFO (HFO group, n = 6) and a combined use of CMV and HFO (combined group, n = 6). Under the same condition as in HFO group, chest was opened and the left pulmonary arterial flow was determined by electromagnetic method (opened thorax group, n = 4). Bilateral lungs were ventilated with pure oxygen during the control period. The right lung was ventilated with pure oxygen while the left lung was ventilated with pure nitrogen afterward during the study. There was no significant change in arterial oxygen partial pressure due to delayed HPV in HFO group or combined group between 30 and 120 minute values. Although there was an increase in mean pulmonary arterial pressure in combined group, in HFO group it was not observed. At the same time, the decrease in pulmonary flow was minimum in open thorax group. Authors conclude that HFO interferes with the effect of HPV to a certain extent. PMID- 2585719 TI - [Anesthetic management of a patient with dermatomyositis--clinical observation of the effect of muscle relaxants]. AB - A 58 year old woman suffering from dermatomyositis underwent elective surgery for spinal caries. Concerning the anesthetic management of patient suffering from dermatomyositis, there is little information on the appropriate use of muscle relaxants. It is generally suspected that the patient is sensitive to nondepolarizing muscle relaxants. Anesthesia was with oxygen-nitrous oxide and fentanyl. Pancuronium 6 mg was given intravenously after awake intubation and an additional dose of 2 mg was given after 7.3 hours. During anesthesia neuromuscular function was monitored by neuromuscular transmission monitor (Datex Relaxograph). Duration of neuromuscular block was defined as the time for the twitch height to recover from total paralysis to 25% of the control value. Duration in this patient was 3.1 hours and this was longer as compared with the values of 1.1-1.8 hours obtained in 7 control patients. It is suggested that a usual dose of muscle relaxants results in a relatively higher effect in the patients with dermatomyositis because of their diminished muscle mass. The anesthetist should be careful in using muscle relaxants. The muscle relaxants should be given to such a patient with monitoring closely the neuromuscular function using a neuromuscular transmission monitor. PMID- 2585720 TI - [A case of reexpansion pulmonary edema during fenestration of a giant hepatic cyst]. AB - We experienced a case of reexpansion pulmonary edema during the fenestration of giant hepatic cyst. The patient was a 56 year-old female who had been suffering from dyspnea due to a large abdominal mass for 3 months. The preoperative chest X ray revealed remarkable elevation of diaphragm (right third and left fifth intercostal spaces). The result of blood gas analysis showed hypoxemia and respiratory compensation for metabolic acidosis. By the drainage of 12L of the cyst fluid for 30 minutes during operation, bloody and foamy bronchial secretion spurted out. Vigorous respiratory management using PEEP was promptly started and continued postoperatively in ICU. The endotrachial tube was withdrawn on the 2nd postoperative day. The ratio of protein in airway secretion in to plasma protein was 0.78, and it appeared that the pulmonary edema was mainly caused by increased permeability of pulmonary capillary vessels. PMID- 2585721 TI - [Isoflurane anesthesia for a child with myotonic dystrophy]. AB - A 5 year-old boy with myotonic dystrophy was anesthetized with isoflurane for bilateral orchiopexy. Intubation was easily done without muscle relaxants, following slow induction using isoflurane, nitrous oxide and oxygen. Myotonia was not observed perioperatively and postoperative course was uneventful. It is concluded that isoflurane is an anesthetic of choice for a patient with myotonic dystrophy. PMID- 2585722 TI - [Anesthesia for a patient with Ehlers-Danlos syndrome and factor XIII deficiency]. AB - Emergency anesthesia was carried out for a patient with Ehlers-Danlos syndrome (type IV) and factor XIII deficiency. The operation was a ligation of the bleeding right subclavian artery. One month later, a transverse colectomy and splenectomy was performed for a necrotic perforation of the colon, but the wound did not heal completely. The patient died of another perforation of the intestine two months later. Anesthetic management of a patient with Ehlers-Danlos syndrome and factor XIII deficiency was reviewed. Particular problems concerning a genetic disease were also discussed. PMID- 2585723 TI - [Cellular thermosensitivity]. AB - (1) modes of expression of thermosensitivity and theoretical interpretation of thermal dose, (2) differential thermosensitivities between strains of cells and the possible correlation to heat shock proteins and their syntheses, (3) cell phase responses to hyperthermia, (4) low hyperthermia and the induction of thermotolerance, (5) comparative thermosensitivities at the temperatures between below and above 42.5 degrees C -43 degrees C, (6) Arrhenius plot and mean cellular lethal heating periods, (7) step-up heating and the thermotolerance induction, (8) step-down heating and the thermoenhancement, (9) fractionated high hyperthermia and the thermotolerance induction and (10) modification of thermosensitivity by chemical substance including anticancer drugs; are compactly reviewed mainly on cell level. PMID- 2585724 TI - [Heat sensitivity of human cancer cells and abnormal expression of heat shock protein 70]. AB - We investigated the heat-sensitivities of human normal and cancer cells at different growth conditions in vitro. We found no difference in sensitivities between normal and cancer cells at growing condition. Normal cells at confluence, however, reduced their heat-sensitivity 5-6 times than at growing condition, while the cancer cells did not. Analysis by monoclonal antibodies for hsp 70 showed the differential staining patterns between normal and cancer cells after treatment with heat (43 degrees C for 2 hours). The constitutive expression levels of hsp 70 in cancer cells were 2-3 times higher than those in normal cells. However, the degrees of hsp 70 induction by heat shock treatment in cancer cells were lower than those in normal cells. These results suggest that cancer cells may be abnormal in expression mechanisms of hsp 70. PMID- 2585725 TI - [Transition of oxic cells to hypoxic cells in a murine squamous cell carcinoma]. AB - (125I) Iododeoxyuridine labeling of a squamous cell carcinoma and follow-up of 125I activity at the tumor in situ revealed that the 125I activity remained at a constant level from the 24th to the 100th hour post-labeling and then decreased with a half time of about 200 hr. Autoradiographic studies with (3H) thymidine showed that the tumor cells were labeled around capillaries, spread through the corded structure (the cord) and finally reached the necrotic regions. One could speculate that the constant 125I period represents the transit time of the labeled cells through the cord and that the decline occurs mostly in the necrotic regions. PMID- 2585726 TI - [Influence of hemoglobin level, arterial oxygen partial pressure and arterial oxygen content on the results of radiation therapy in lung squamous cell cancer]. AB - It is believed that anemia is an important prognostic factor in the case of cancer patients treated by radiation therapy. One possible explanation for this is tumor oxygenation. With respect to tumor oxygenation, the arterial oxygen content (CaO2) may be more direct indicator than hemoglobin (Hb) level. Fourty two patients with squamous cell lung cancer treated solely by irradiation were reviewed. It was found that CaO2 was more important than the Hb level in determining a tumor response to radiation therapy. This is considered as important indirect evidence of the existence of hypoxic fractions of cells in human tumors. PMID- 2585727 TI - [Prediction of radiosensitivity by micronucleus assay]. AB - The correlation between cell survival curve and dose response curve of MN frequency following irradiations was studied using cytokinesis-block method. Both dose response curves were analyzed by linear quadratic model, i.e. SF = exp (- alpha D - beta D2) and MN frequency = aD + bD2 + c. A good correlation between alpha/beta and a/b ratios was observed in repeated paired experiments (gamma = 0.97). When the cells were treated with BUdR, alpha-type radiosensitizer, a value in dose response curve of MN frequency increased but b value did not. In 10 renal cell carcinomas, the linear correlations between cell surviving fractions and MN frequencies were observed. When radioresponses of 5 esophageal cancer cell lines were evaluated with MN assay, wide range of a/b ratios was found. These data present that MN frequency assay using CB method is available as a tool of rapid assay of radiosensitivity of cells. PMID- 2585728 TI - [Prediction of radiosensitivity by DNA analysis]. AB - The aim of the study is to investigate the relationship between DNA histogram and radiosensitivity on tumor specimens taken directly from patients. Flow cytometric DNA content analysis with PI (Propidium iodide) was performed on specimens of cervical carcinoma. Radiosensitivities of respective tumors were determined on biopsy specimens that were taken 3 weeks after the start of radiotherapy. Five parameters (over 4C, %G2M, %S, PI, DI) were calculated from DNA Histogram. Among these parameters over 4C, %G2M and PI correlated well to radiosensitivity. PMID- 2585729 TI - [Subrenal capsule assay applied to prediction of tumor radiosensitivity]. AB - The radiation responses of murine fibrosarcomas with different radiosensitivities (MCA-induced fibrosarcoma and NFSa), human tumors transplanted into athymic nude mice (HeLa, HMV-I and SNG-II) and fresh surgical sample of human tumor (seminoma) were investigated using the subrenal capsule assay with immuno-competent C3H/He, C57BL and ICR mice as host. Mice were immuno-suppressed by the combination of cyclophosphamide and cyclosporin A. Tumor growth-speed of each transplant under the renal capsule of mice was much greater than that of the subcutaneous counterparts. Tumor responses under the renal capsule to radiation were well correlated with the known radiosensitivities of the tumors. Above findings indicate that the subrenal capsule assay is a feasible method to predict the radiation response of a tumor. PMID- 2585730 TI - [Interstitial radiotherapy of carcinoma of the tongue-comparison between Jacobson Yamamoto grading and prognosis]. AB - One hundred and one patients of less than seventy years old with T1, T2 and N0 carcinoma of the tongue were graded according to the Jacobson-Yamamoto's grading (1-4 D). All patients were also classified into two groups such as less than fifty years old group and fifty to seventy years old group. Patients with grade 3, 4 C and 4 D carcinoma had more metastases to the cervical lymph nodes than grade 1, 2. Patients with T2N0 carcinoma showed approximately same five year cervical lymph node metastases free survival rate. However, the five year survival rate of less than fifty years old group was significantly lower than that of fifty to seventy years old group. In T2N0, grade 3-4 D carcinoma cases, more dead cases were found in less than fifty years old group than in fifty to seventy years old group. PMID- 2585731 TI - [Prognostic factors in patients with brain metastases from lung carcinoma]. AB - Between September 1980 to December 1984, 85 patients with brain metastases from lung carcinoma were consecutively evaluated and were entered into the first prospective randomized trial. Since January 1985, the second prospective randomized trial was started based on the result of the first trial, i.e., lactate dehydrogenase (LDH) as the most important prognostic factor. We analyzed neurological improvement and survival of 79 patients, who were entered into the second trial until November 1988, compared with the first trial. This preliminary result suggests that LDH may also be an important prognostic factor in the second trial. PMID- 2585732 TI - [Study of prognostic factors in patients with cervix carcinoma treated by radiotherapy]. AB - One hundred and eighty-one patients who were treated by irradiation only for carcinoma of uterine cervix were analyzed to evaluate for cure or recurrence, by the multidimensional quantification theory II. The cases were also restricted to primary T3b in TNM classification, large tumor volume, squamous cell Ca. for the histology, cure and residual primary or recurred tumor and less than 76 years old at first therapy. In 181 cases, 116 were cure and 65 were residual or recurred cases. Finally, 7 prognostic factors which were consisted fever during treatment, age at the first examination, function of kidney, tumor dose at point A, horizontal inclination of the Tandem, growth type of tumor and reduction of body weight were significantly related to the recurrence. PMID- 2585733 TI - [Prognostic factors of common epithelial ovarian cancer treated by surgery and cisplatin based combination chemotherapy]. AB - Retrospective analysis of prognostic factors in 171 patients who had common epithelial ovarian cancer (WHO) and treated by surgeries and cisplatin based combination chemotherapies were performed by survival assay and multivariate analysis. In FIGO stage 3, the estimated parameter values were in following order: residual tumour age grade performance status histological type. On analysing Stage patients, histological grading and histological typing had an effect on prognosis. Patients with grade 2 or tumours had a worse prognosis than did those with grade 1 tumours, and patients with clear-cell carcinoma or undifferentiated adenocarcinoma showed a poor prognosis. PMID- 2585735 TI - [Tissue selectivity of Ca-antagonist]. PMID- 2585734 TI - [Classification of Ca antagonist by its chemical structure and characteristics of each derivative]. PMID- 2585737 TI - [Calcium kinetics and effects of calcium antagonist on vascular smooth muscle]. PMID- 2585736 TI - [Intracellular calcium messenger system and drug action]. PMID- 2585738 TI - [Effect of Ca2+ antagonists on coronary circulation]. PMID- 2585739 TI - [Calcium channel blockers and cerebral circulation]. PMID- 2585740 TI - [Pulmonary circulation and Ca-antagonists]. PMID- 2585741 TI - [Pharmacokinetics and dynamics of Ca-antagonists in relation to the development of their slow release formulas]. PMID- 2585742 TI - [New approach to the development of Ca antagonists]. PMID- 2585743 TI - [Calcium antagonists in the treatment of hypertension]. PMID- 2585744 TI - [Calcium antagonists in the treatment of angina]. PMID- 2585745 TI - [Use of calcium antagonists in cardiac arrhythmias]. PMID- 2585746 TI - [Treatment of congestive heart failure using Ca blockers]. PMID- 2585747 TI - [Treatment of cardiomyopathy using Ca blockers]. PMID- 2585748 TI - [Clinical application of calcium antagonists in the treatment of cerebral infarction]. PMID- 2585749 TI - [Antiepileptic action of Ca antagonist, flunarizine]. PMID- 2585750 TI - [Antiatherosclerotic effects of Ca2+ antagonists]. PMID- 2585751 TI - [New basic and clinical aspects of endocrine and metabolic diseases]. AB - New findings obtained from basic research works using novel techniques in protein analyses, molecular biology and applied chemistry have broadened the knowledge of pathophysiological and biochemical aspects in various endocrine disorders, which often led to establishment of new diagnostic and/or therapeutic approaches. Among many interesting recent topics in endocrinology, the following themes were chosen in this symposium entitled "basic and clinical aspects of certain endocrine and metabolic diseases": ACTH secretion in adrenocortical disorders by Dr. Ohgo, pregnancy and PRL secretion by Dr. Miyakawa, auto-antigens in autoimmune thyroid diseases by Dr. Kotani, new active D3 derivatives and their clinical application in bone disorders by Dr. Okamoto, pathophysiological roles of atrial natriuretic peptide (ANP) in hypertension by Dr. Kida, and recent trends in diagnosis and treatment of diabetes mellitus by Dr. Sugiyama. We believed that each lecture covered and clarified new developments and their clinical implications, which should satisfy and stimulate your interest. PMID- 2585753 TI - [A colorimetric method for determination of delta-bilirubin in serum using bilirubin oxidase (Trachyderma tsunodae)]. AB - We developed a colorimetric method to measure delta-Bilirubin in human serum using bilirubin oxidase from Trachyderma tsunodae and diazo reagent. In the first step, bilirubin fractions except for delta-Bilirubin, such as diconjugated, monoconjugated and unconjugated forms, are removed by enzymatic oxidation at pH 8.0 in the presence of sodium salicylate. In the second step, delta-Bilirubin remaining after enzymatic oxidation is determined by the conventional indirect diazo method. The results obtained by this method showed intra-day CV of 2.4%, satisfactory linearity and good correlation (r = 0.93, p less than 0.001) with those obtained by high performance liquid chromatography method. This simple and rapid method was clinical useful for determining the bilirubin fractions in sera of hepatic patients. PMID- 2585752 TI - [Prolactin and pregnancy]. AB - The role of prolactin during fetal growth and lung maturation was investigated in humans. Prolactin levels in the maternal, fetal and amniotic compartments were measured by radio-immunoassay in patients with anencephalic fetuses, and patients treated with bromocriptine during pregnancy. Bromocriptine or an active metabolite(s) passed through the term placenta and suppressed prolactin secretion by the fetal pituitary gland. Prolactin levels in amniotic fluid were scarcely affected by bromocriptine treatment. This suggested that prolactin in amniotic fluid was not derived from biosynthesis of the dopamine receptor-mediated process. The maternal and fetal prolactin may not play an obligatory role in the maintenance of pregnancy and fetal growth. PMID- 2585754 TI - [Enzymatic determination of a molar ratio of free branched-chain amino acids to tyrosine (BTR) and its clinical significance in plasma of patients with various liver diseases]. AB - A molar ratio of free branched-chain amino acids to tyrosine (BTR) was determined in the plasma of patients with liver diseases using a new enzymatic method. In addition, clinical significance of BTR was studied by comparing particularly with that of Fischer's ratio (a molar ratio of branched-chain amino acids to aromatic amino acids (tyrosine+phenylalanine], which was obtained by conventional HPLC (Amino acid autoanalyzer, Hitachi 835). Following results were obtained: 1) Enzymatically determined branched-chain amino acids and tyrosine showed significant correlations with respective results obtained by HPLC (r = 0.937, 0.972). 2) Significant correlation was also found between enzymatically determined BTR and Fischer's ratio obtained by HPLC. Changes of BTR in clinical courses were found to be in parallel with those of Fischer's ratio. 3) BTR as well as Fischer's ratio correlated significantly with ICG R15, KICG, prothrombin time (%) and serum albumin level. 4) BTRs in patients with decompensated liver cirrhosis or with fulminant hepatitis were significantly lower than those in patients with acute or chronic hepatitis. In conclusion, new enzymatic assay of branched-chain amino acids and tyrosine as described here is quite simple method, and is also considered to be very useful parameter of the clinical conditions of patients with liver diseases, particularly representing the severity of liver diseases and the protein nutritional status. PMID- 2585756 TI - [ELISA for platelet-associated IgG, IgM, and C3, and their clinical application]. AB - The platelet-associated IgG (PAIgG) has been reported to elevate in the patients with idiopathic thrombocytopenic purpura (ITP) and other autoimmune diseases. However, low PAIgG levels have been often recognized in thrombocytopenia. We speculated about the increasing of other platelet-associated proteins in those patients, and tried to determine platelet-associated IgM (PAIgM) and platelet associated C3 (PAC3) using a high sensitive competitive micro-ELISA as well as PAIgG. Our results showed the specific elevation of PAIgM and PAC3 in thrombocytopenia as well as the PAIgG level (p less than 0.01). Further, the weak correlations among these levels were found (PAIgG/PAIgM: n = 7, correlation coefficient (r) = 0.55, PAIgG/PAC3: n = 73, r = 0.61, PAIgM/PAC3: n = 56, r = 0.39). We discussed on the possibility that the PAIgM and PAC3 also could be an indicator for the platelet injury and may cause the short platelet life span resulting thrombocytopenia as well as PAIgG. PMID- 2585755 TI - [Isolation of Legionella spp. from cooling tower water and the effect of microbicides]. AB - Legionella spp., the causative organism of legionnaires' disease, were isolated from more than 80% of water samples in cooling towers before washing. Therefore, we evaluated the effect of microbicide treatment of cooling tower water on Legionella spp., other bacteria and protozoa. 2-Bromo-2-nitropane-1,3-dial, 2,4 dibromo-5,5-dimethylhydantoin or silver nitrate-treated silica gel was added to cooling tower water. The isolation rate of Legionella spp. in the cooling tower water was 50% after microbiocide treatment with 2-bromo-2-nitropane-1,3-dial being the most effective. The microbicide treatment had no effect on other bacteria or protozoa. These findings indicated the importance of regular washing and water exchange of cooling tower water with microbicide treatment. PMID- 2585757 TI - [Pulmonary function in normal Japanese children 6 to 16 years of age]. AB - We measured pulmonary function on 182 healthy Japanese children 6 to 16 years of age living in the Tokyo area. Static lung volumes, RV/TLC (%), FRC/TLC (%), FVC, FEV1, FEV1/FVC (%), MMFR, MVV, f, VE and VO2 were measured. Multiple regression equations were obtained and the results were compared with those derived from the other equations (Kanagami (1958), Ishida (1955]. The predicted values were about 10 approximately 25% higher with our equations than those obtained from the other equations which were made more than 30 years ago. These differences were attributed to the recent improvement in growth of the Japanese children. For this reason we think it is better now to adopt new equations for the prediction of normal values in Japanese children. PMID- 2585758 TI - [A case of chronic neutrophilic leukemia with abnormal karyotype]. AB - A 75-year-old man was admitted to our hospital because of leukocytosis and thrombocytosis. The peripheral blood showed RBC 403 x 10(4)/microliters, Hb 14.1 g/dl, PLT 91 x 10(4)/microliters, and WBC 48,000/microliters with a differential count of 24% band forms, 65% segmented forms and 11% others. The bone marrow aspiration revealed myeloid hyperplasia (94.4% myeloid series, 4.8% erythroid series and 0.8% others), and NAP score was consistently high. The serum level of lysozyme and vitamin B12 were elevated. There were no signs of infection or other malignancy. Cytogenetic study of bone marrow cells showed mosaic karyotypes of 46,XY/46,XY,t(7;16) (q22;q24). The Ph1 chromosome was not found. A diagnosis of chronic neutrophilic leukemia was made. Serial chromosomal analysis showed the coexistence of a clone with 46,XY,t(7;16) (q22;q24) and that with 46, XY. PMID- 2585759 TI - [MRI and ultrasonography of cavernous hemangioma of the liver]. AB - The frequency of detection of hemangioma has increased with the improvements of ultrasonography. Sonography detected 24 lesions out of 30 (80%), and 28 lesions out of 30 (93%) by MRI. MRI is superior to ultrasonography in detection rate. In T2 weighted spin echo image, most of the hepatic hemangiomas show moderately or markedly higher intensity than the liver and mildly higher or the same intensity as that of the spleen. MRI will play an important role in determination of necessity of further invasive diagnostic methods such as angiography or biopsy. PMID- 2585760 TI - [The usefulness of 99mTc-PMT cholescintigraphy in the diagnosis of bile leakage or biloma]. AB - 5 cases (6 lesions) of bile leakage or bilomas were experienced. All cases showed high accumulative areas in the lesions of bile leakage using 99mTc-PMT cholescintigraphy, while US and CT studies showed no specific findings of fluid filled areas. Cholescintigraphy demonstrated communications between the injured biliary systems and other spaces very clearly. Even if the needle aspiration failed to get a characteristic bile, which were sometimes seen in bilomas complicated with infection or bleeding, cholescintigraphy was useful for the accurate diagnosis. It is also useful for monitoring the bile drainage. PMID- 2585761 TI - [Long-term effects of partial splenic embolization (PSE) for hypersplenism]. AB - 24 cases of hypersplenism were treated by PSE using Gelfoam particles. In cases with 90% embolized, the mean WBC and platelet counts were improved for 5.0 and 3.4 months. In cases with over 60% embolized, those were improved for 19.6 and 19.3 months. 9 cases with over 60% embolized remain in good condition more than 2 years, especially 2 cases of them remain more than 3 years. One patient with total embolized developed a splenic abscess and died after one month from PSE. But another severe complications were not shown. PMID- 2585762 TI - [A case of planum sphenoidale destruction due to cystadenoma of the ethmoid bone]. PMID- 2585763 TI - [Ruptured nonparasitic liver cyst caused by blunt abdominal trauma]. AB - Three patients with ruptured nonparasitic liver cyst (two with suspected multiple liver cysts and one with polycystic disease) following blunt abdominal trauma were described. Ultrasonographic examinations and computed tomography (CT) scans were useful in evaluating the presence and degree of liver injury, the amount of hemoperitoneum and the need for operative repair. Two patients with intraperitoneal bleeding were treated by transcatheter hepatic arterial embolization and all three patients were successfully managed nonoperatively. PMID- 2585765 TI - [Hepatic reticuloendothelial failure: report of a young heavy-drinker case]. AB - A 27-year-old-male with hepatic reticuloendothelial failure was reported. He was proved by laparoscopy as having alcoholic liver cirrhosis. In spite of the absence of hepatic colloid uptake, hepatobiliary scan with Tc-99m HIDA and Ga-67 citrate produced satisfactory liver images. PMID- 2585764 TI - [Two cases of small intrahepatic arterial aneurysm]. AB - Two cases with intrahepatic aneurysms were experienced. One was associated with hemobilia, the other was found incidentally. These aneurysms had angiographic appearance of pseudo-aneurysm, and occurred in peripheral branches of hepatic arteries, that are rare location for aneurysm formation. Causative factor was demonstrated in neither of the cases. PMID- 2585766 TI - [A case of porto-caval shunt via pancreatico-duodenal vein and right ovarian vein -effectiveness of MRI]. AB - A case of hepatic encephalopathy due to portal hypertension with a rare porto caval shunt was presented with special reference to MRI. Markedly dilated collaterals of pancreatico-duodenal vein and right ovarian vein were clearly revealed in MRI or PTP. MRI is useful and indispensable to evaluate various porto systemic communications. PMID- 2585767 TI - [Prophylactic embolization for unruptured aneurysm of the splenic artery; a case report]. AB - A 67-year-old woman with liver cirrhosis underwent computed tomography (CT). The CT scan incidentally disclosed a large aneurysm of the splenic artery. Then, embolization therapy was performed using steel coils. No complications occurred. Usefulness of prophylactic embolization for unruptured aneurysm of the splenic artery was reported. PMID- 2585769 TI - [Clinical analysis of anti-cardiolipin antibody positive patients with systemic lupus erythematosus]. AB - We have analyzed the relationship between anti-cardiolipin antibody titer and manifestations in 68 patients with systemic lupus erythematosus (SLE), 25 patients with progressive systemic sclerosis (PSS), 37 patients with Sjogren's syndrome and 16 patients with anaphylactoid purpura. Elevated anti-cardiolipin antibody titer was observed in SLE and Sjogren's syndrome. Clinical manifestations correlated with elevated anti-cardiolipin antibody titer included discoid lesion, thrombotic lesion, thrombocytopenia, elevated titer of ds-DNA antibodies, lower serum CPK level, and liver dysfunctions. Anti-cardiolipin antibody titer also correlated with the score of diagnostic criteria for SLE and the history of corticosteroid therapy. These results suggested that anti cardiolipin antibody positive SLE patients are much more prone to develop thrombotic lesions and that cell bound antibody might play some role for the induction of vascular injury and thrombocytopenia in SLE. PMID- 2585768 TI - [Effects of dihydrotestosterone on cultured hair papilla cells and localization of its receptors]. AB - We have reported that cultured papilla cells (PC) grown by isolation and cultivation of human hair papillae show some biological characteristics. In the present study, localization of androgen binding proteins in PC and effects of dihydrotestosterone (DHT) on PC in vitro were examined. Cytochemical staining of PC using DHT-peroxidase conjugate gave positive reactions in the nucleo of PC originating from scalp- and axilla-hair papillae. The cultivation of PC with added DHT in media for two weeks showed increases 3H-thymidine uptake and 14C proline uptake over that of dermal fibroblasts. These results suggest that androgen receptors exist in PC and that DHT in culture media induces an accelerating effect upon the DNA synthesis and protein synthesis. PMID- 2585770 TI - [Intraepidermal distribution patterns of melanocytes in the melanocytic lesions on the sole: proposed criteria for histopathologic diagnosis of plantar malignant melanoma in situ]. AB - Eighty-eight melanocytic lesions on the soles of Japanese were histologically investigated. Increased numbers of solitary melanocytes above the basal layer of the epidermis were often found in the benign melanocytic nevi on the sole: in 5 lesions of 9 congenital melanocytic nevi, 22 of 65 acquired melanocytic nevi, and 1 of 5 dysplastic nevi. In addition, a moderate degree of nuclear atypia of proliferating melanocytes was frequently observed in the benign melanocytic nevi on the sole: in 3 lesions of 9 congenital melanocytic nevi, 17 of 65 acquired melanocytic nevi, and 2 of 5 dysplastic nevi. Therefore it cannot be said that increased numbers of solitary atypical melanocytes above the basal layer is a characteristic histologic feature of early malignant melanoma in situ. Combining the intraepidermal distribution patterns of melanocytes and maximum diameter of the lesion, we propose criteria for histopathologic diagnosis of plantar malignant melanoma in situ. PMID- 2585771 TI - [A new variety of neurocutaneous melanosis: benign leptomeningeal melanocytoma associated with extensive Mongolian spot on the back]. AB - A 38-year-old Japanese man presented with a blue macule on the back. A spinal meningeal tumor at the C3-C5 levels was detected radiologically and excised. The histological findings in the biopsy specimen from the blue macule were consistent with an extensive Mongolian spot. The histological diagnosis of the meningeal tumor was benign melanocytoma. The case was thought to be a new variety of neurocutaneous melanosis. PMID- 2585772 TI - [Neoplastic angioendotheliosis: a case of T cell lymphoma positive for S-100 protein]. AB - A 63-year-old woman presented with painless, firm, subcutaneous nodules on her legs and trunk. The lesions were annular or serpiginous and their surface was livid-red to pale-red. Superficial lymph nodes were not palpable. Upper gastrointestinal series, barium enema, Ga scintigraphy, and CT findings were negative. Histological examination revealed deep dermal vessels occupied by neoplastic cells and fibrin thrombi. We diagnosed her as having neoplastic angioendotheliosis. Electron microscopically, tumor cells lacked Weibel-Palade bodies. Immunohistochemically, the tumor cells were positive for leukocyte common antigen, T11, MT-1, HLA-DR and S-100 protein. They were negative for Factor VIII related antigen, epithelial membrane antigen, carcinoembryonic antigen, B-1, and B-2. Immunoelectron microscopic study showed that their nuclei, cytoplasma, and cell membranes were positive for S-100 protein. Based on these findings, we diagnosed her as having T cell lymphoma. The patient rejected chemotherapy and was discharged. Three months after discharge, right hemiplegia developed. Brain CT scan revealed enhanced masses in the left frontal, temporal, and occipital lobes. Craniotomy showed only gliosis and hemorrhage. She died of cerebral bleeding three months after craniotomy. PMID- 2585773 TI - [T-cell lymphoma of the skin--clinicopathological relationships, therapy and survival]. AB - We investigated the pretreatment characteristics and prognosis of T-cell lymphomas, including mycosis fungoides (MF), T-cell lymphoma of the skin other than MF (CTL), adult T-cell leukemia/lymphoma (ATL), immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma and angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), as well as B-cell lymphoma of the skin (CBL) and analyzed the prognostic factors for skin T-cell lymphoma when the skin was the organ initially or predoienantly involved. Twenty-eight cases of erythematous stage MF, ten cases of plaque-stage MF, eleven cases of tumor-stage MF, twelve cases of ATL, eleven cases of IBL-like T-cell lymphoma/AILD, and eight cases of CBL were studied. CTCL patients were treated by photochemotherapy with topical 8 methoxypsoralen (8-MOP) followed by VUA irradiation, electron-beam irradiation, or systemic chemotherapy. Complete remission (CR) was obtained with all of these therapies. However induction of CR was not a major prognostic factor in skin T cell lymphoma, and the clinical stage was more valuable in this respect. No cases of death occurred among erythematous-stage MF patients, but eight out of 11 patients with tumor-stage MF died (mean survival rate, 38 months). The prognosis for tumor-stage MF was better than that of ATL (19 months) or IBL-like T cell lymphoma/AILD (28 months), but worse than those of erythematous-a plaque-stage MF. TNM staging of CTCL was also a useful factor for prognosis. PMID- 2585774 TI - [Electron microscopic and immunohistological studies of a case of Ehlers-Danlos syndrome type IV]. AB - A 5-year-old male considered clinically to have Ehlers-Danlos syndrome (EDS) type IV with main symptoms of fragility and easy bruisability of the skin was presented. Electron microscopic observations of collagen fibers and immunohistological examination of the localization of the type III collagen in the patient revealed dissimilarities in the size and the irregularities in the shape of collagen filaments, as well as a clear difference in localization of type III collagen when compared with normal skin of same age. PMID- 2585775 TI - [A case of psoriasis vulgaris whose lipoprotein lipase activity decreased during treatment with etretinate]. AB - Treatment with etretinate is known to be effective for patients with psoriasis. However, it has been reported that the administration of etretinate often generates side effects which disturb lipoprotein metabolism. In this study, 5 patients with psoriasis vulgaris were treated with etretinate (1 mg/kg/day), and the changes in serum lipids, apolipoprotein levels, and lipoprotein lipase (LPL) activity were observed. In 4 out of the 5 cases, the above determinations were within the normal range throughout the course. However, in the case of one 35 year old man, LPL activity markedly decreased on day 28 after the administration of etretinate and was restored when the administration was suspended. Furthermore, LPL activity decreased again when the administration was resumed. Therefore, it appeared that the decrease of LPL activity in this case was mainly due to the administration of etretinate. PMID- 2585776 TI - [Correlation of activated T cells and natural killer (NK) cells with the disease activity of alopecia areata (AA)]. AB - Patients with AA were classified into one of two types (Type A: active AA with less than 3 patches; Type B: active AA with 10 or more patches). The percentages of activated T cell subsets and NK cell subsets in the peripheral blood of Type A were similar to those of the normal control. On the other hand, the percentages of HLA-DR+ Leu2a+ cells, HLA-DR+ Leu3a+ cells, Leu7+ Leu11+ cells and Leu7- Leu11+ cells in Type B were significantly higher than those of the normal control. These findings suggest that activated T cells and NK cells play an important role in the disease activity of AA. PMID- 2585777 TI - [Establishment of a human skin squamous cell carcinoma cell line (SCC-1CB) in vitro and its characteristics]. AB - A human skin tumor cell line SCC-1CB has been established in vitro. A specimen from a surgically excised tumor with moderately differentiated squamous cell carcinoma of skin from a Japanese male, aged 62, was transplanted subcutaneously into nude mice. After growth, a part of the tumor was passaged with a transplantation needle. At the fourth passage, part of the tumor was explanted into culture dishes. Cell cultures were maintained in Eagle's minimal essential medium supplemented with 10% fetal calf serum. A SCC cell line (SCC-1CB) was cloned and then established. Chromosome analysis revealed the human type with a mode number of 56. The cell line is tumorigenic in nude mice. Immunohistochemical staining revealed that keratin, cytokeratin and vimentin were positive and desmin was negative. It can be cryopreserved in liquid nitrogen. It has successfully maintained proliferation in continuous cell culture for over 2.5 years. The cells retain their original morphological appearance as determined by light and electron microscopy. PMID- 2585778 TI - [Significance of LDH isozyme pattern in rubella]. AB - The laboratory data from 136 patients suffering from a mass outbreak of rubella were serially examined. Alteration of thrombocytopenia (38.7%), leukopenia (26.4%), increased LDH (94.3%), and increased GOT (32.4%) were observed during the early days of disease. Slightly later, increased GPT was noted in 48.5%. LDH isozymes may be grouped into two specific patterns: 1) an LDH3 dominant pattern appeared (90.4%) during the beginning days of the disease. 2) an LDH3 dominant pattern with LDH5 greater than LDH4 was detected one week later. It was concluded that the increase of LDH3 may have been induced by thrombocytopenia due to viral infection. The increase of LDH5 appears to result from liver damage. In conclusion, LDH isozyme findings are significant in the early diagnosis of liver damage in rubella. PMID- 2585779 TI - [Production of human monoclonal auto-antibodies which recognize skin components]. AB - Using human myeloma cell line, LICR-LON-HMy2, and human lymphocytes, we have produced human monoclonal auto-antibodies against skin-components by human-human hybridoma technique. Resulting monoclonal antibodies are classified as follows; 1. Antibodies which recognize cytoplasmic filamentous antigen(s) in epithelial and non-epithelial cells, which are presumably keratin cross-reacting with other classes of intermediate filament(s), 2. Antibody to keratinocyte cellular membrane which is specific to upper epidermal layers, 3. Antibody to sebaceus gland with some cross-reaction in horny layers, 4. Antibody to the innermost cell layer of outer root sheath. The immunoglobulin class of all the antibodies was human IgM. Although pathological roles of these monoclonal antibodies are unknown, it is suggested that auto-antibodies against skin components are more commonly produced in human than previously understood and may be associated with various skin diseases. PMID- 2585780 TI - [Localization in skin, activation and reaction mechanisms of skin sulfhydryl oxidase]. AB - S-S cross-linking enzyme, skin sulfhydryl oxidase (SSO), catalyzes the formation of disulfide bonds from sulfhydryl groups in skin. The activity of SSO was detected in differing amounts in each of the four layers--stratum corneum, stratum granulosum, stratum spinosum with basal cell layer, and dermis--of cow snout skin, with the highest specific activity being recorded in the stratum granulosum. SSO was stimulated to 130-150% of its initial activity by treatment with 1 mg/ml trypsin, chymotrypsin, or urokinase, but was not affected by plasmin or cathepsin D. These findings suggest that SSO may be activated by some kinds of serine proteases during the keratinocyte autolysis process in the stratum granulosum. SSO showed the highest activity with the addition of 5 microM of Cu2+. The atomic absorptive analysis of purified SSO showed 0.5 atoms of Cu in one molecule of SSO. From these findings, it was determined that Cu2+ was essential for the activity of SSO. The molar ratio of the disappearance of DTT, consumption of O2, and production of H2O2 during the enzyme reaction was 1:1.05:0.89. From these findings, the reactions catalyzed by SSO is suggested to be represented by the following equation: (table; see text). PMID- 2585781 TI - [Treatment of skin symptoms of Behcet's disease with low dose cyclosporin A]. AB - We treated six patients with moderate to severe skin symptoms of Behcet's disease with oral administration of Cyclosporin A (CsA). During the first two weeks, 5 mg/kg/day CsA twice a day was given and then the dose was reduced to 3 mg/kg/day. Erythema nodosum like eruptions, oral aphtha, and thrombophlebitis began to improve within three days, and four patients had complete remission by two weeks after the start of treatment. In one patient, a genital ulcer took almost three months to disappear. In peripheral blood of patients treated with CsA 5 mg/kg/day for two weeks, there were decreases in the OKT4/OKT8 ratio. After the reduction of the dosage, the ratio was temporarily increased, but it decreased to the normal range around the twelfth week of the treatment. No clinically important side effects were seen. PMID- 2585782 TI - [Primary tissue culture of nevus cell nevus--in comparison with the findings from neurofibroma culture]. AB - Forty-two nevus cell nevi excised surgically from 40 patients were processed for primary culture. The characteristic features of cultured nevi were compared with those of neurofibroma reported previously. 1) Based on phase-microscopic findings, S-100 protein staining, and slow motion picture, most of the cultured macrophage-like cells or cells with dendrites were considered to be nevocytes. 2) The emigration of nevocytes was observed in 31 of the 42 nevus cultures (73%). Nevocytes classified histologically as the intradermal type with fatty degeneration and nevi obtained from the face and aged patients exhibited higher tendencies to ward emigration when they were cultured. 3) The cultured Schwann cells in neurofibroma and the nevus cell nevus, mainly c-type nevocytes, are both of neural crest origin. They were observed to have closely similar morphological and S-100 protein staining features. PMID- 2585783 TI - [Two cases of infantile subungual pigmented nevi with Hutchinson's sign]. AB - Two cases of subungual pigmented nevi with periungual melanotic freckles, namely Hutchinson's sign, are presented. They are a 4-year-old female and a 11-month-old male; in neither case did the mother notice the lesion at birth. Histologically, both cases were characterized by the presence of well-circumscribed small nests of nevus cells in the periungual melanotic areas; diagnoses of junctional nevus and compound nevus were made, respectively. However, atypical proliferations of melanocytes at the dermo-epidermal junction of the nail matrix and nail bed were observed in some areas. The measurement of the DNA content of melanocytes by means of microfluorometry revealed normal diploid pattern in the former case, but the latter case contained a few aneuploid cells, suggesting that the proliferating melanocytes might have malignant potentials. Infantile subungual pigmented nevi with Hutchinson's sign must be examined thoroughly and watched carefully. PMID- 2585784 TI - [A case of hereditary angioneurotic edema associated with systemic lupus erythematosus]. AB - A 33-year-old woman noticed recurrent and sudden attacks of subcutaneous swelling of the extremities and face since the age of 4 years. Sometimes the attacks involved colicky abdominal pain. Her mother and younger sister had episodes of recurrent swelling of the extremities as well. Complement studies revealed low CH50, C1q, C4, and C1 inhibitor levels, with normal C3 and C5 levels. Similar reductions of CH50 C4 and C1 inhibitor levels were observed in her mother, older, and younger sisters. Therefore, she was diagnosed as hereditary angioneurotic edema. In addition, she was diagnosed as having a butterfly rash at the age of 20 years and had a history of solar sensitivity. Histologically the facial lesion showed liquefaction degeneration of the basal cell layer. Direct immunofluorescent staining of the affected skin lesion showed basement membrane zone staining of IgG and IgM. Laboratory studies revealed lymphopenia and positive ANF. On the basis of the above findings, hereditary angioneurotic edema associated with systemic lupus erythematosus was diagnosed. PMID- 2585785 TI - [Gastric ulcer formation induced by kainic acid injection into the dorsal motor nucleus of the vagus nerve (DMN) and identification of the neuronal input to the DMN in rats]. AB - Parasympathetic preganglionic cells innervating the stomach are located in the dorsal motor nucleus of the vagus nerve (DMN) in the medulla. The present experiments were carried out to elucidate that the long-lasting excitation of DMN neurons by kainic acid, a long-acting neuronal excitant, induced gastric ulcers and to identify the input neuronal systems projecting to the DMN by means of horseradish peroxidase (HRP) method in rats. Twenty four hours after kainic acid injection into the DMN, gastric ulcerative lesions were induced in 12 out of 14 rats. The ulcer index in experimental group, 10.2 +/- 6.5 mm, was significantly higher than that in the control group, 0.5 +/- 1.0. Mucus content in gastric mucosa was significantly lower than that of the control group. Fourty four hours after HRP injection into the DMN, HRP labeled cells were distributed from medulla to cortex, especially in medullary reticular formation, interpositis cerebellar nucleus, several hypothalamic nuclei, central amygdala nucleus and insular cortex. These results suggest that long-lasting excitation of DMN neurons facilitate gastric ulcer formation and that a decrease in mucus content in gastric mucosa plays an important role in the process of gastric ulcer formation by kainic acid injection into the DMN. Since the cortex, amygdala and hypothalamus has been shown to be closely associated with emotion and stress, it could be speculated that emotional changes and stress might induce the changes of excitability of DMN neurons via higher order neuronal systems. PMID- 2585786 TI - [Effect of body position on gastric emptying of solid food--a study using a sulfamethizole capsule food method]. AB - We studied the effect of body position on gastric emptying of solid food using a sulfamethizole capsule food method developed by us. Gastric emptying was significantly delayed in a supine position than in a sitting position kept for 120 minutes after ingestion of test food. These findings were observed in all of the young, middle and old aged groups. A longer sitting position after ingestion was associated with faster gastric emptying. Gastric emptying was significantly delayed in the old aged group than in the young aged group in both sitting and supine positions. Our results indicate that a postprandial sitting position is desirable for gastric digestion and emptying of solid food, especially in the old aged subjects. PMID- 2585787 TI - [Immunocytochemical characterization of the DNA-polymerase alpha-positive colonic mucosal epithelial cells in patients with ulcerative colitis]. AB - Colonic mucosal epithelial cells (EpC) in patients with ulcerative colitis (UC) have been shown to express HLA-DR antigen. In the present study, we observed the characteristics of HLA-DR-positive EpC using immunoperoxidase technique. In the control group, colonic EpC expressed HLA-ABC, but not HLA-DR. Only the EpC at the base of glands revealed positive for DNA-polymerase alpha (DNA-P). On the other hand, in actively inflamed mucosa of UC, about 80% of glands strongly expressed HLA-DR. Furthermore, most of EpC in the HLA-DR-positive glands showed positive nuclear stainings for DNA-P. This indicates that these EpC are not in the resting stage. It is strongly suggested that there are close relationships between the regeneration or proliferation of the EpC and class II MHC (HLA-DR) expression on the EpC in UC. PMID- 2585788 TI - [The role of bile acids with physiological concentration in colon carcinogenesis]. AB - The promoting effect of bile acids in physiological concentration in colon carcinogenesis was studied using male Wistar rats with defunctioned colon. After an instillation of MNNG, collected rat faces (group A), secondary bile acids i.e. deoxycholic acid and lithocholic acid in equal concentration to rat feces (group B) and control material (group C) was instilled in the defunctioned colon. Concerning the incidence and the number of macroscopically visible tumor, no significant difference was found among these three groups. However, the number of histological lesion with atypia in flat mucosa of the colon in group A and B was significantly greater than that in group C. Considering this result and the results obtained from prestudy of kinetics of colonic epithelial cells by the use of anti BrdU monoclonal antibody, feces and physiological concentration of bile acids had a promoting effect in colon carcinogenesis. PMID- 2585789 TI - [Ultrastructural study of interlobular bile ductal disorganization in autoimmune liver diseases]. AB - Ultrastructures of interlobular bile ductules were examined in 7 cases of lupoid hepatitis and related disease (LH) and 8 cases of primary biliary cirrhosis (PBC). Mononuclear cell, especially lymphocyte infiltrations into bile ducts cross basement membrane were common findings found in 57.1% of LH and in 50% of PBC patients, thus, statistically, the occurrence of lymphocyte infiltration was similar for both groups. Cell contact between bile duct epithelia and infiltrated cells differed in LH and PBC. In LH, 86.7% of the cells contacted at small point, but 92.3% PBC cells had broad contact with each other. Stratification of bile duct epithelia and other visible changes in PBC epithelial cells was statistically more extensive compared with LH. Dilatation of intercellular space was often observed in basal region of LH. Destruction and degeneration of LH and PBC bile duct epithelial cells was mainly observed in basal and luminal regions, respectively. Rupture and thickening of basement membrane was seen in PBC, but rarely in LH. The average diameter of interlobular bile ducts were larger and oval shaped in patients with PBC compared to smaller circular ducts observed in LH patients. These results not only revealed that several changes in interlobular bile ducts occur but that similar changes with LH and PBC. This suggests that both distinctions and similarities exist between LH and PBC as autoimmune hepatic disease. PMID- 2585790 TI - [Effects of supplementation with branched-chain amino acids on protein nutritional status in rats treated by carbon tetrachloride]. AB - A study was conducted to investigate effects of oral supplementation with branched-chain amino acids (BCAA) on protein-nutritional status in rats with liver cirrhosis. Liver cirrhosis was induced in male strain Sprague-Dawley rats by simultaneously administrating carbon tetrachloride (500 mg/kg, twice a week, intracutaneously) and phenobarbital (0.05% in drinking water, ad libitum) for 30 weeks. Following treatment with carbon tetrachloride and phenobarbital, cirrhotic rats received oral supplementation of BCAA with varying ratio among isoleucine (Ile), leucine (Leu) and valine (Val), or with varying content of total BCAA in the diet (Final content of total nitrogen was kept consistent by addition of glutamine). Nutritional efficacies of diets as described above were evaluated employing those protein-nutritional parameters as nitrogen balance and plasma levels of total protein, albumin and free neutral amino acids. Following results were obtained: 1. Compositional ratio of Ile:Leu:Val at 1:2:1.2 or at 2:1:1 was found to be more effective on diets which contained ILe:Leu:Val at 1:1:2 or either Val, Ile or Leu alone. 2. As to content of total BCAA in the diet (0, 2.5, 5, 10%), supplementation level of 2.5% was found to be most appropriate in terms of effects on nitrogen balance and on plasma protein concentration. In conclusion, 2.5% BCAA in the diet with the ratio of Ile:Leu:Val at 1:2:1.2 or 2:1:1 seems to be recommended to improve the impaired protein-nutritional status in liver cirrhosis. PMID- 2585791 TI - [Long-term follow up of a case of superior mesenteric artery embolism]. PMID- 2585793 TI - [A case of carcinoma of the papilla Vater associated with multiple intramural bile duct cysts and polycystic disease]. PMID- 2585792 TI - [A case of alcoholic liver injury associated with acute alcoholic myopathy]. PMID- 2585794 TI - [Portal vein thrombosis following splenectomy successfully treated with thrombolytic therapy]. PMID- 2585795 TI - [Microspectrophotometric DNA analysis in ulcerative colitis with special reference to its application for cancer and dysplasia diagnosis]. AB - The DNA content was measured by microspectrophotometry from 100 specimens in 60 patients with ulcerative colitis including six complicating carcinoma. In dysplastic 23 (77%) of 30 samples showed aneuploidy or polyploidy, whereas in non dysplastic tissues 50 (94%) of 53 samples were diploid, the difference being statistically significant. Polyploidy was often observed in the non-dysplastic mucosa of the patients complicating cancer or dysplasia. In non-dysplastic patients all samples with inflammation showed diploidy, however 10% of samples without inflammation showed polyploidy. A good correlation was found between the incidence of polyploid cells and the grade of dysplasia. From this study it was assumed that microspectrophotometric measurement of DNA content is useful in the assessment and diagnosis of dysplasia in ulcerative colitis and can be available in the screening of high-risk patients. PMID- 2585796 TI - [Effect of vasopressin on rabbit hepatic energy metabolism evaluated using in vivo P-31 magnetic resonance spectroscopy]. AB - Changes in metabolic state of rabbit livers after administration of vasopressin (10 mU/kg/min d.i.v.) were evaluated using in vivo P-31 magnetic resonance (MR) spectroscopy. Targets were nine normal control rabbits and eight with chronically carbon tetrachloride-damaged livers. A 2.0 Tesla whole-body MR imager was used for measurement. After administration of vasopressin, liver spectroscopy showed a mild ischemic pattern. The inorganic phosphate peak increased statistically significantly (p less than 0.05) both in the normal control group and in the damaged-liver group (20% and 16% above base line value respectively). In the normal control group, there was a statistically significant decrease (p less than 0.05) in the ATP peak to 18% below the base line value while the PME (phosphomonoester) peak increased slightly (about 10%); there was little change in the damaged-liver group. It was thought that the difference between the two groups was due to differences in blood flow mechanism and liver metabolism. Magnetic resonance spectroscopy was considered to be useful in studying the detailed changes in metabolic state of rabbit liver after administration of vasopressin. PMID- 2585797 TI - [Pancreatic exocrine secretion and plasma gut hormones response after intraduodenal infusion of elemental diet in patients with chronic pancreatitis]. AB - We studied the responses of pancreatic polypeptide (PP) and cholecystokinin (CCK) using specific RIAs, and simultaneously exocrine pancreatic secretion and gall bladder contraction were checked by using triple lumen tube to intraduodenal ingestion of 100 Kcal/hr semi-digested liquid meal: Clinimeal (Eisai, Tokyo) or Elemental Diet: ED (Morishita, Osaka) in 10 patients with chronic pancreatitis (CP). Intraduodenal infusion of Clinimeal did not result in a significant physiological rise of CCK and PP from the basal values. Pancreatic secretions (volume and bicarbonate output) were slightly increased paralleled to the gall bladder contraction in chronic pancreatitis. On the other hand, intraduodenal ED can significantly stimulate the release of CCK from the small intestine and PP from the pancreas with the near range of physiological concentration. This level of CCK can evoke a significant increase in pancreatic secretion and gall bladder contraction. These results suggest that in CP the physiological regulation was disturbed and pancreatic secretion was not observed after ordinary meal ingestion. Infusion of ED which contained similar components of digestive product partially improved the responses of gut hormones and pancreatic secretion. Therefore, impaired gut hormone release in CP primarily is due to the inappropriate stimuli because of pancreatic exocrine dysfunction, and not other factors(s). PMID- 2585798 TI - [A case of amyloidosis secondary to Crohn's disease]. PMID- 2585799 TI - [A case of intestinal strongyloidosis complicated with massive intestinal bleeding]. PMID- 2585800 TI - [Successful hepatic artery embolization to control massive jejunal bleeding from the hepatic artery pseudoaneurysm]. PMID- 2585801 TI - [A female case of alcoholic liver cirrhosis with rapid progress from alcoholic fatty liver]. PMID- 2585802 TI - [New treatments for ulcerative colitis and Crohn's disease]. PMID- 2585803 TI - [Burnout syndrome of human services professionals--doctors, nurses, caregivers, teachers and clerks (1). Maslach Burnout Inventory: factor structures for samples of human services professionals, and its relation with Zung's Self-rating Depression Scale (SDS)]. AB - During the past decade, burnout syndrome has been widely discussed not only in the USA but also in Japan. To evaluate the state of "burnout," two major scales are available: the first is the Maslach Burnout Inventory (MBI) developed by C. Maslach and the other is the burnout scale by A. Pines. MBI is suggested to be independent of and incompatible with Pines' burnout scale, but, Pines' burnout scale is predominantly used in Japan, while both are used in the USA. Since hardly any studies of burnout using MBI have been made in Japan, we measured and analyzed MBI to evaluate the burnout state of doctors, nurses, caregivers, teachers and clerks who are engaged in "human services professions." The available data were subjected to factor analysis, reliability analysis and multiple regression analysis using Zung's Self-rating Depression Scale (SDS). The following results were obtained. 1) The factor analysis showed that the factor loading pattern was similar to that of Maslach's, but two different factors were emerged in addition to the standard factors in the intensity subscale. 2) In the relationship with the state of depression, burnout is closely related to depression but simultaneously has its own factors. This suggest that burnout is not a subtype of the depressive state. PMID- 2585805 TI - [Assessment of occupational exposures to industrial hazardous substances. IV. A proposed method based on one-sided tolerance limits]. AB - Occupational exposures to potentially hazardous substances may vary considerably because of interday environmental behavioral fluctuations in the contaminant concentration. Such occupational exposures including those of non-monitored days can be theoretically evaluated by the following three ways: 1) assessment of geometric mean and geometric standard deviation, 2) assessment of arithmetic mean, and 3) assessment of upper limits of daily exposure distribution. In our previous report, an evaluation method on 95% upper limit or arithmetic mean of exposures was proposed. The method is useful, particularly, in case where only one or two days are being monitored, but may provide an approximate estimate because of statistical assumption. A sampling and decision scheme using one-sided tolerance limits (OTL) proposed by Tuggle (1982) can precisely evaluate the upper limits of exposures. However, many cases would be evaluated as "no decision," unless the sample size is extremely large in number. We developed a revised method based on OTL for assessment of occupational exposures. The characteristic features of this method can be summarized as follows: 1. Upper limits of lognormally distributed 8-h exposure concentrations can be evaluated in comparison with an established standard. 2. A third OTL factor was introduced into Tuggle's scheme in which two OTL factors were used. A comparison between the upper limits of exposures and the standard can be made at 50% confidence level with the factor. The factor was calculated using non-central t-distribution. 3. The usefulness of the third OTL factor in the assessment of occupational exposures was confirmed by examining the performance characteristics of the method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585804 TI - [Assessment of occupational exposures to industrial hazardous substances. III. On the frequency distribution of daily exposure averages (8-h TWA)]. AB - A method based on interday fluctuation of contaminant concentrations for evaluating employee's exposure averages (8-h TWAs) was proposed in our previous report. The method was established on the assumption that daily exposure averages of the workers are lognormally distributed in actual workplaces. The study was conducted to elucidate whether the distribution of daily exposure averages is statistically lognormal or not and to examine the relationship between sample geometric standard deviation (sg) of worker's daily exposure averages and its estimate (sg2) calculated by measurements for two consecutive days. These are critical for our proposed method. The data on daily exposure concentrations over five to six weeks were collected from workers exposed to cobalt, acetone, n hexane, toluene, xylene, ethylbenzene and ethylacetate. The data on organic lead, inorganic lead and mercury exposures reported by Cope et al. and Lindstedt et al. were also used for the study. The result can be summarized as follows: 1. Lognormal distribution of daily exposure averages was confirmed by plotting on normal probability paper and chi 2-test. 2. Median of sg2 on daily exposure averages obtained from individual worker was smaller than sg. 3. sg calculated by a set of measurements for two consecutive days in every worker can be corrected by the equation: (sg2) 1.48 in obtaining a better estimate of sigma g. 4. Statistical analysis on daily exposure averages of all workers showed that median of sg2 was smaller than that of sg, and 88% upper limit of sg2 was equal to that of sg. 5. Therefore, in evaluating TWA obtained by only single day's measurement using the proposed method, median of sg representative of industrial hazardous substance exposure workplaces could be also corrected by the equation described above. However, correction of 90% upper limit of sg2 is not necessary. PMID- 2585806 TI - Comparison of hair with nail as index media for biological monitoring of mercury. AB - Mercury in hair and nails was determined with speciation of chemical forms of mercury. Scalp hair and toenails were sampled once and fingernails were sampled three times from the subjects (18 males and 5 females) whose age ranged from 23 to 56 yr. Total mercury (THg) and inorganic mercury (IHg) were determined by Magos' method with modifications. No sex-related differences were found in mercury levels in hair and nails. In the fingernail samples of three different formation periods, THg and IHg concentrations remained almost constant. Among the three kinds of index media, the highest THg concentration was found in scalp hair followed by fingernails and toenails in the order given, whereas IHg concentrations in scalp hair were similar as those in fingernails but were lowest in toenails. The percent inorganic to total mercury was higher in fingernails than in hair and toenails, which is likely to reflect a possible external contamination with IHg in fingernails. The higher THg concentration in scalp hair than in nails may be attributable to the difference in the chemical composition, in particular sulphur content, and in the blood flow during the formation of hair and nails. PMID- 2585807 TI - [Delta-aminolevulinic acid in blood as an indicator of early health effect of lead]. PMID- 2585808 TI - [Allergic conditions among workers in poultry processing industry]. PMID- 2585809 TI - [A portable sampler for oil mist in machine workshops]. PMID- 2585810 TI - [A new pocket-type flicker apparatus]. AB - A small, light and inexpensive pocket flicker (P.F.) apparatus for measuring fatigue was designed, fabricated and tested. The apparatus, being composed of a light emitting diode and a variable resistor with a scale, is so compact that it can be carried in a shirt pocket. Thus, critical fusion frequency (CFF) values can be easily determined at a working place and the load involved is small when compared to other physical fatigue measurements and earlier CFF apparatuses. Moreover, the apparatus is so inexpensive that it can be widely used. To compare the performance of the P.F. apparatus with earlier apparatuses, the following experiments were performed. CFF values were measured at the same time with the pocket type apparatus, blinking type apparatus and sector type apparatus and the results were compared. The subjects were 13 males and 5 females with their age ranging from 21 to 52 years. The total number of measurements was 132. The CFF values measured with these three apparatuses showed a significant correlation. The correlation coefficient between the CFF values measured with the sector type apparatus and blinking type apparatus was high, but the slope of the regression line was not one. Hence, in comparing the values measured with another apparatus, we should be aware of the differences between these data. The correlation coefficients between the CFF values measured with P.F. apparatus and with sector type apparatus or blinking type apparatus were not higher than those between the CFF values measured with sector type apparatus and blinking type apparatus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585811 TI - Effect of benzene and its metabolites on natural killer activity of mouse spleen cells in vitro. AB - The effects of benzene and its metabolites, phenol and hydroquinone, on natural killer (NK) activity in mouse spleen cells in vitro were studied. NK activity was evaluated by the specific release percentage of 51Cr from labeled YAC-1 cells after YAC-1 cells (target cells) were incubated with spleen cells (effector cells) of mice at ratios of effector cells to target cells (E/T) of 100/1, 50/1, and 25/1. Benzene was shown to inhibit NK activity at concentrations of 1 x 10( 5) M-5 x 10(-5) M, phenol at concentrations of 1 x 10(-7)-5 x 10(-5) M and hydroquinone at concentrations of 1 x 10(-6) M-1 x 10(5) M. Phenol and hydroquinone depressed NK activity in a dose-dependent manner. This study demonstrated that NK cell function of mouse spleen was depressed by exposure to benzene and its metabolites in vitro. Hydroquinone and phenol have very potent toxicity for suppression of immunosurveillance. PMID- 2585812 TI - [A physiologically based pharmacokinetic model to describe the transfer of organic solvents in the human body. Simulation of kinetic behavior of trichloroethylene using a spreadsheet program]. AB - A physiologically based pharmacokinetic model was developed to describe the transfer of organic solvent vapors in the human body. The model was composed of seven tissue compartments, i.e., lungs, vessel-rich tissues, vessel-poor tissues, muscles, fat tissues, gastrointestinal tissues, and liver, each being interconnected by the blood flow system. Transfer of organic solvents was expressed in the form of simultaneous differential equations, which were then solved numerically on a personal computer using a simple spreadsheet program. The simulation of pharmacokinetic behavior of trichloroethylene with this model was found to be in general agreement with the experimental data. The usefulness of a physiological simulation model to elucidate some toxicokinetic aspects of human exposure to organic solvent vapors is discussed. PMID- 2585813 TI - [The relationship between external and internal doses of trichloroethylene. A simulation study using a physiological pharmacokinetic model]. AB - The relationship between external dose and internal dose of trichloroethylene (Tri) was analyzed by using a physiological simulation model. The external dose of Tri was represented by the time-weighted average (TWA) concentration in inhaled air or by the product of exposure concentration and exposure duration, and the internal dose by the area under the curve (AUC) of Tri blood concentration or by the cumulative amount of total trichloro compounds (TTC) in urine. If TWA concentrations were equal, the internal doses were also equal irrespective of whether Tri exposure was continuous, intermittent, or random. Both AUC of Tri and cumulative amounts of urinary TTC increased linearly with increase of Tri concentration in inhaled air up to 100 ppm. The increase at exposure concentrations between 100 and 500 ppm was non-linear. At concentrations above 500 ppm where Tri metabolism was saturated, AUC increased linearly again but much more sharply than the increase at concentrations below 100 ppm. In contrast, the increase of cumulative amounts approached a plateau along with Tri exposure concentration. If the exposure concentration was below the level when saturation of Tri metabolism did not occur, equal products of Tri concentration and exposure duration resulted in almost the same internal dose. In general, however, the AUC of blood concentration in a high-concentration, short-duration exposure was larger than that of a low-concentration, long-duration exposure, whereas the cumulative amount of TTC was larger in the latter than in the former. PMID- 2585814 TI - [Individual differences in the kinetic behavior of trichloroethylene. A simulation study using a physiological pharmacokinetic model]. AB - Toxicokinetic behaviors of trichloroetylene were analyzed by using a physiological simulation model and the effects of physical activity (work load), body fat content and alcohol consumption on the uptake, distribution and excretion of this solvent were studied. This simulation study was not intended to predict the exact kinetic behavior of trichloroethylene in man, but to show how a physiological pharmacokinetic model is used to elucidate some aspects of individual differences in the kinetics of organic solvent vapors in human exposure. The following results were obtained: 1. Physical activity of 50 W during exposure greatly increases the blood concentration of trichloroethylene and the urinary excretion of its metabolites, whereas the activity after exposure exerts only a marginal influence. 2. Body fat content substantially affects the kinetic behavior of trichloroethylene only when the blood flow through fat tissue is assumed to increase according to the increase in body fat volume. In general, both blood concentration of trichloroethylene and urinary excretion rate of its metabolites are higher in slim men than in obese men during exposure, and the relationship is reversed between obese and slim men after exposure. 3. Ethanol induced inhibition of trichloroethylene metabolism causes a marked change in the kinetic behavior when trichloroethylene exposure level is low, whereas the greater is the effect of ethanol-induced enhancement of metabolism, the higher the exposure level. PMID- 2585815 TI - [Health care of workers engaged in waste water treatment. 1) The exposure conditions to organic solvents in workers engaged in waste water treatment]. AB - In the investigation of the exposure conditions to organic solvents of workers in 35 waste water treatment facilities, it was found that these workers treated various kinds of solvents. Almost all of the facilities treated chloroform, acetone, n-hexane, methanol and carbon tetrachloride. The average exposure concentration of the workers was, however, low. Exposure concentration to organic solvents (chloroform, xylene and carbon tetrachloride) was evaluated in one of the facilities. The average concentration of the respective solvents in the workers did not exceed the threshold limit value of Japan, but the concentration calculated on the basis of combined exposure exceeded the threshold limit value. On the other hand, high concentrations of organic solvents were detected in the room where the solvents were introduced but not in the working rooms, indicating that the workers engaged in waste water treatment were mainly exposed to organic solvents in the former room where they sorted and mixed the solvents and placed them in the incinerator. In conclusion, improvement in working conditions and health care for workers engaged in waste water treatment facilities should be made in order to prevent workers from becoming intoxicated by organic solvents. PMID- 2585816 TI - [The effects of prenatal trimethyltin exposure on development and learning in the rat]. AB - Developmental effects of single prenatal trimethyltin exposure were examined in THA rats. Pregnant rats were injected on gestational day 12 with single dose of trimethyltin chloride (TMT) ip at either 0, 5, or 7 mg/kg. Significant differences between treated and control offspring rats could not be observed in terms of body weight, pinna detachment, incisor eruption, eye opening, surface righting, cliff avoidance, pivoting, negative geotaxis and auditory startle. Spontaneous motor activity and open field behavior in the rats were also not affected by TMT. In Sidman avoidance test, however, the avoidance rate of the treated offspring rats was lower when compared to that of the controls. These results suggest that prenatal TMT administration disrupts learning acquisition. PMID- 2585817 TI - Macroscopic changes seen in human erythrocytes heated in a suspension and the resulting effect on their blood group activity. AB - Changes in the macroscopic appearance and in the activity of various erythrocyte antigens were observed by heating human erythrocytes of known blood groups at 60 260 degrees C for 15, 30, and 60 min in a suspension that was sealed in an airtight test tube. While the erythrocytes underwent severe hemolysis after heating at 60 degrees C, this phenomenon was not macroscopically observed on heating at 80 and 100 degrees C and the cellular sludge in the tested became brown in color. With further temperature increases, the supernatant became pale yellow at 120-140 degrees C, brown at 160 degrees C and dark brown at 180 degrees C and above, whereas the sediment hardened and became darker in tone. Both A and B activity in the cellular sludge remained active until a 30-min heating at 240 degrees C, as did the O(H) activity until a 15-min heating at 220 degrees C. Both Lewis type activity was detected until a 30-min heating at 200 degrees C and a 15 min heating at 220 degrees C. The P1 activity remained specific after a 30-min heating at 180 degrees C and false-positive reactions were observed after 60 min at 180 degrees C. Among the Rh antigen activity, D activity remained until a 60 min heating at 140 degrees C, C and E until a 30-min heating at 140 degrees C, c until a 15-min heating at 140 degrees C and e until a 30-min heating at 100 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585818 TI - Distribution of Gm allotypes among the three populations of the Miyako Islands in Okinawa. AB - Serum samples from 738 unrelated individuals of three populations in the Miyako Islands were tested for twelve Gm allotypes to investigate the variability of phenotypes and haplotypes. Nine phenotypes observed in these populations as well as mainland Japanese could be explained by the presence of the four Gm haplotypes, ag, axg, ab3st, and afb1b3. A good agreement was obtained in the samples of each populations between the observed and expected frequencies on the basis of the Hardy-Weinberg equilibrium of phenotypes. These populations showed remarkable heterogeneities with one another on the basis of Gm haplotype frequency analysis. Moreover they exhibited no homogeneities with the Ryukyuans nor with the mainland Japanese. Homogeneity was found between the Ainu and the people in Ueno village but not in the other two locations. However, Gm xg haplotype, only detected in the Ainu, was not found in Ueno. These may imply a racial relationship between the Ainu and the inhabitants in Miyako in the remote past. However, there is no certainty that both of Ainu and the people in Ueno derived from the same origin, or that genetic drift due to endogamy in this village took place. The Gm phenotype and haplotype frequencies observed in Miyako show that they belong to the northern mongoloid group characterized by a high frequency of Gm ag and an extremely low frequency of Gm afb1b3. It is therefore reasonable to assume that they came from northern Asia as well as mainland Japanese. PMID- 2585819 TI - A new method for the determination of ethanol in the blood and urine by pulse heating. AB - We have established a new method for the determination of ethanol and other gaseous substances in even minute amounts of biological material by utilizing a Curie-point pyrolyzer (Model JHP 3, Japan Analytical Industry) connected to GC or GC-MS. No pretreatment of the biological material is needed and the procedure is based on the principle that volatile or gaseous substances can be evaporated from biological materials by pulse heating and introduced for analysis directly to a GC or GC-MS. The blood from rats that had been administered ethanol-d6 orally, as well as blood and urine collected from healthy volunteers that had ingested alcoholic drinks and blood and tissue specimens taken from autopsied cadavers were examined for ethanol concentrations by both this new method and by the usual head space-GC method. To test this new method, one microliter of the blood or urine was injected into a tubularly folded ferromagnetic alloy (Pyrofoil) and heated pulsatively five times at 160 degrees C (pulse heating). The vapor that evaporated from the sample then was directly introduced to the GC or GC-MS, and the time required to complete the analysis took approximately 5 min. In parallel, for comparison purposes, portions of the same samples (0.2-0.5 g) were examined by means of the head space method as well. The measured values of ethanol-d6 and ethanol in the rat blood and in the human whole blood, blood plasma, and urine that were obtained by this pulse heating procedure correlated almost perfectly with those obtained by head space method. These results show the accuracy and reproducibility of this new method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585820 TI - Applicability of an immuno-microsphere technique for a forensic identification of ABO blood types: the use of fluorescent microspheres. AB - In order to develop a direct micro-method for the ABO blood typing of forensic samples, an attempt has been made to utilize fluorescent immuno-microspheres. Microspheres (Covaspheres MX and CX particles, Duke Scientific) were coupled with partially purified antibodies from commercial mouse monoclonal anti-A, anti-B, and anti-H reagents, as well as with affinity purified UEA-I. The reactivity and specificity of the immuno-microspheres were checked with fresh erythrocytes of known blood groups, after which the spheres then were applied to the typing of hemolyzed and thermo-changed erythrocytes and bloodstains. The microspheres coated with the monoclonal antibodies and the UEA-I showed specific and distinct reactions with fresh, hemolyzed and thermo-changed erythrocytes, and bloodstains. Further, by combining particles labelled with different dyes, the possibility of a simultaneous double-labelling of the group antigens was indicated on the fresh cells and on the hemolyzed and thermo-changed cells and cell fragments. PMID- 2585821 TI - Sudden unexpected death from a superior mesenteric venous thrombosis after a gastrectomy. AB - Reported are the autopsy findings of a 55-year-old man who died unexpectedly 20 h after a subtotal gastrectomy of an early gastric cancer. The cause of his death was a superior mesenteric venous thrombosis, involving his small bowel which manifested a marked vascular engorgement. The entire small bowel mesentery was thickened and edematous, and hemorrhagic infarctions were scattered near the bowel. Many fresh thrombi could be identified in the superior mesenteric veins. This case is described, together with the legal aspects of medical malpractice. PMID- 2585822 TI - Anti-A-like and anti-B-like cold auto-hemagglutinins in a patient with malignant lymphoma and healthy individuals. AB - A cold auto-hemagglutinin with anti-B-like specificity was found in the serum of a group B patient with malignant lymphoma. The auto-hemagglutinin reacted only with B (adult) red cells and was inhibited by B secretor saliva. The appearance of this hemagglutinin in the patient's serum was transient. The presence of cold auto-hemagglutinins with anti-A-like and/or anti-B-like specificities was also demonstrated in sera from 15 (14.4%) of 104 group A1B healthy Japanese adults. The immunological features of these cold auto-hemagglutinins were similar to those of the anti-B-like hemagglutinin in the patient with malignant lymphoma. PMID- 2585823 TI - [Intrarenal energy metabolism in ischemic renal injury in rabbits]. AB - In order to clarify the cause of the decrease in the urinary excretion of NAG (U NAG) in severe ischemic renal injury in rabbits, we studied intrarenal energy metabolism in ischemic renal injury. After 5 min of ischemia, energy charge and ATP significantly decreased by 50% and 29% respectively. These parameters, however, did not significantly show the change in more than 5 min of renal ischemia. Energy charge and ATP did not reflect the degree of renal injury produced by ischemia, while it was indicated that the longer the period of ischemia until 120 min of ischemia, the less the rate of intrarenal ATP resynthesis at 30 min after reflow. Intrarenal lactate content increased significantly from the 5 min ischemia group to the 180 min. These results suggest that no improvement in intrarenal energy metabolism with increasing duration of renal ischemia is showed and ischemic renal injury develops progressively. It is probable that the decrease in U-NAG in severe ischemic renal injury is due to the inability of the kidney to wash out NAG into the urine, although NAG may be released from the injured tubular cells in proportion to ischemic renal injury. Therefore, in spite of severe ischemic renal injury, U-NAG may show low values, and may lead to misjudgement that the proximal tubular cells are intact. U-NAG should be measured repeatedly and estimated in association with the other renal function tests, especially creatinine clearance, for the correct evaluation of ischemic renal injury. PMID- 2585824 TI - [The effects of sairei-to on nephrotoxic serum nephritis in rats--possible effects on intraglomerular cell mediated immunity]. AB - Sairei-to, one of the herb drugs, has been demonstrated to have several effects. Clinically, evidence have been accumulated showing that sairei-to has been able to reduce the frequency of relapse in minimal change nephrotic syndrome. It has also found that sairei-to has improved proteinurial in minimal change nephrotic syndrome as well as chronic glomerulonephritis in man. Although the mechanism of such effects is still unclear, it is supposed that its immune modulating actions that has been reported. In this study, we quantitated the number of intrarenal Ia positive cells and T cells in nephrotoxic nephritis in rats in order to clarify the intrarenal immune actions of sairei-to on immune mediated glomerulonephritis. Four groups of rats with nephrotoxic nephritis were experimented on. The first group was the controlled group, had no treatment whatsoever. The second group was administered with MPSL (solu-medrol 20 mg/kg, alternate day). The fourth group with both sairei-to and MPSL. The level of proteinuria in three groups treated was almost the same, that is, less than that of controlled group. On light microscopy, sairei-to suppressed glomerular inflammation such as endocapillary proliferative lesions and mesangial expansion, which were shown in controlled group. The histological improvement was almost the found in rats treated with MPSL and both. Sairei-to suppressed infiltrations of intraglomerular Ia positive cells (P less than 0.01) and T cells (P less than 0.01) on the 7th day and 14th day as well. Remarkable suppression of T cells infiltration was noted in rats treated with MPSL along with sairei-to on the 14th day (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585825 TI - [Studies of cell-mediated immunity in mesangial proliferative glomerulonephritis- IgA nephropathy and non-IgA nephropathy]. AB - In order to clarify the abnormalities of cell-mediated immunity in patients with mesangial proliferative glomerulonephritis [IgA nephropathy (IgA N) and Non-IgA nephropathy (Non-IgA N)], lymphocyte subsets were analysed by using monoclonal antibodies with flow cytometric two-color analysis and interleukin-2 (IL-2) production from lymphocytes of the patients was measured by ELISA system. A markedly decreased percentage (11.6 +/- 10.5%) of CD4+ 45R+ cells was found in the patients with IgA N when the results were compared with the normal controls (20 +/- 6%) (P less than 0.01). No difference was found between patients with IgA N and the controls as to the percentage of CD4+ 45R-, CD8+, 11+ and CD8+ 11- cells, respectively. Patients with Non-IgA N also showed a significantly decreased percentage of CD4+ 45R+ cells (10.9 +/- 6.5%), while CD8+ 11+ cells was parallely lowered (7.4 +/- 5%) in compared with the controls (10 +/- 4%). The percentage of HLA-DR positive cells was found to be increased in the patients with both IgA N and Non-IgA N, although the antigen bearing cells were reduced after stimulation with Concanavalin-A (Con-A). No difference in IL-2 production from lymphocyte of both patients groups and the controls cultured with Con-A was found. These results suggested that a deficiency of suppressor inducer T cells played a part of the pathogenesis of IgA N and Non-IgA N. PMID- 2585827 TI - [Discriminant analysis of clinical markers before renal biopsy in patients with IgA nephropathy]. AB - Discriminant analysis of clinical markers before renal biopsy in patients with IgA nephropathy is described. Sixty eight patients with IgA nephropathy (IgA nephropathy group) and 66 patients with other chronic glomerulonephritis (non-IgA nephropathy group) were examined. The discriminant analysis was applied to separate those two groups by using twenty clinical parameters as well as binding capacity of serum IgA to the glomeruli of renal specimens. Binding of serum IgA of patients to the glomeruli obtained from patients with IgA nephropathy was performed using avidin-biotin immunofluorescence. Among twenty clinical markers, the levels of serum IgA and creatinine, and degree of microhematuria in IgA nephropathy group were significantly higher than those in non-IgA nephropathy group Furthermore, the positive incidence of serum IgA binding of IgA nephropathy group was significantly higher than that of serum IgA binding of non-IgA nephropathy group. The correct classification rate were 79.10% using five clinical markers including serum IgA, microhematuria, serum C4, quantitation of proteinuria and degree of proteinuria. It is indicated that the levels of serum IgA and the binding of serum IgA to the glomeruli were considered to be major markers for clinical diagnosis of patients with IgA nephropathy It was concluded that the discriminant analysis before renal biopsy was useful for diagnosis of IgA nephropathy. PMID- 2585826 TI - [Comparative studies of clinicopathological findings in patients with adult and juvenile onset of IgA nephropathy]. AB - Comparative studies of clinicopathological findings were carried out in 89 patients with adult and juvenile onset of IgA nephropathy. Among 89 patients with IgA nephropathy, there were 42 patients with juvenile onset, i.e less than 19 years old, and 47 patients with adult onset, i.e. more than 35 years old. Clinical activities of both groups were examined as follows; urinary protein, mean blood pressure renal function (PSP 15 min, Ccr) and serum IgA (s-IgA). The histology of renal tissues was also examined by light microscopy and immunofluorescence in both groups. The levels of mean blood pressure or s-IgA in patients with adult onset group were significantly higher than those in patients with juvenile onset group (p less than 0.001). The levels of Ccr in patients with adult onset group were markedly decreased. The patients with more than 1.0g/day of proteinuria and more than 110 mmHg of mean blood pressure showed severe proliferative glomerular injuries by light microscopy. It is suggested that the patients with adult onset of IgA nephropathy show severe progressive and/or exacerbating factors during the clinical course. PMID- 2585828 TI - [Serological and histological study of lupus nephritis with special reference to anti-SSA antibody]. AB - Systemic lupus erythematosus (SLE) is a disease of unknown etiology in which many organs are damaged by deposition of pathogenic autoantibodies and immune complexes Clinically lupus nephritis occurs about 50% in SLE Many studies revealed the association between autoantibodies and lupus nephritis However, the pathogenetic role of autoantibodies in lupus nephritis remains obscure. To elucidate the pathogenetic role of anti-SSA antibody in lupus nephritis, 32 patients with SLE were evaluated by serological and histological methods. Enzyme linked immunosorbent assay for anti-SSA antibody was developed for this study. It was confirmed that this assay was specific, did not detect autoantibodies other than anti-SSA antibody. The levels of anti-SSA antibody determined by this assay significantly correlated with the levels determined by double immunodiffusion (p less than 0.01). The level of anti-SSA antibody greater than or equal to 200 units was regarded as positive. The serum levels of antinuclear antibody, anti DNA antibody, anti-RNP antibody, anti-SSA antibody, anti-SSB antibody, C3, and C4 were also determined. Renal biopsy materials were evaluated according to the WHO criteria, and activity index (AI), chronicity index (CI), and pathologic score (PS) were calculated according to Austin et al. The patients were divided into group A (AI greater than or equal to 4, n = 17) and group B (AI less than or equal to 3, n = 15) The levels of anti-DNA antibody were significantly higher in group A than in group B (p less than 0.05). The frequency of positive anti-SSA antibody in group A (70.6%) was greater than in group B (23.3%) significantly (p less than 0.05). However, there were no differences in the levels of anti-nuclear antibody, anti-DNA antibody, anti-RNP anti-body, anti-SSA antibody, anti-SSB antibody, C3, and C4 between group A and group B. Then these patients were divided into group I (anti-SSA greater than or equal to 200 units, n = 17) and group II (anti-SSA less than 200 units, n = 15). AI and CI were greater than in group I than in group II significantly (p less than 0.05). The frequency of pericarditis in group I (35.3%) was greater than group II (6.7%) (p = 0.061), but the frequencies of the other clinical manifestations were not different. AI was correlated with anti-DNA antibody significantly (p less than 0.01), but there were no correlations between other serological data and parameters.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2585829 TI - [Erythropoiesis and hemolysis in hemodialysis patients]. AB - In order to investigate the pathogenesis of renal anemia, erythroid marrow cellularity, factors affecting erythropoiesis and hemolysis, hemolysis starting point by Parpart method and red cell life-span were studied in 21 patients undergoing hemodialysis (HD). Mean value of serum erythropoietin level (EPO) in HD patients was 28.4 mU/ml, which value was nearly equal to that in healthy subjects. Total erythroblast count was higher than normal up to 25.2% in HD patients with Ht below 25% (A group), on the other hand, in HD patients with Ht above 25% (B group) it was 21 6%, nearly equal to normal. Total erythroblast counts positively correlated to EPO level, but did not correlate to ribonuclease, aluminium and parathyroid hormone. Red cell life-span was 23.4 days in A group, and it was 19.8 days in B group Hemolysis starting point was observed at 0.61% NaCl in B group, and at 0.56% in A group. Hemolysis starting point negatively correlated to red cell life-span, but did not correlate to BUN, serum creatinine and serum guanidino compound. Hb level negatively correlated to nuclear cell counts of bone marrow in HD patients, and positively correlated to hemolysis starting point. These results suggested that erythroblast count was controlled by both erythropoietin and hemoglobin levels in HD patients. Hemoglobin level in HD patients was maintained by balance of counteracting factors between erythropoiesis and hemolysis. PMID- 2585830 TI - [An echocardiographic study of cardiac function in chronic hemodialysis patients]. AB - Echocardiography was studied in 83 uremic patients on maintenance hemodialysis and 18 normal subjects. Cardiac systolic and diastolic functions were evaluated according to Yamaguchi's method. Systolic functions such as ejection fraction and fractional shortening decreased in the patients receiving hemodialysis for less than 3 months. However, they remained within normal range in the patients under hemodialysis for more than 3 months. There were no significant correlations between systolic functions and mean blood pressure or various serum biochemical parameters such as urea nitrogen, creatinine, Na, K, Ca, P, hematocrit and PTH-C. Diastolic functions such as rapid filling rate/endosystolic volume, mean velocity of circumferential fiber lengthening during rapid filling, diastolic descent rate and diastolic posterior wall velocity also decreased in the patients receiving hemodialysis for less than 3 months. However, they increased slightly in the patients under hemodialysis for more than 3 months, although they were still lower than those in normal subjects. They were not related to mean blood pressure or various serum biochemical parameters. Hemodialysis patients had left ventricular hypertrophy regardless of duration of hemodialysis. Diastolic dysfunction in hemodialysis patients seemed to be due to systolic dysfunction, left ventricular hypertrophy and diminished ventricular compliance with myocardial degeneration. It was also suggested that increasing slow filling and atrial contraction in diastole might be related to diastolic dysfunction. These cardiac changes may be compensatory reactions of cardiac muscle to various uremic environments such as anemia, hypertension, fluid retention, electrolytes disturbance or uremic toxins. PMID- 2585831 TI - [Studies on the mechanism of glomerular localization of immune complexes (1). Localization of preformed native ferritin immune complexes on the glomerular basement membrane in passive serum sickness nephritis of mice]. AB - Immune complex deposits found on the subepithelial side of the glomerular basement membrane (GBM) are characteristic of membranous glomerulonephritis. In order to clarify the mechanism of subepithelial immune complex deposition, we investigated the manner of localization of preformed immune complexes (IC) composed of native ferritin (NF) and anti NF antibody (aNFab) in a 40-fold antigen great excess using the system of passive serum sickness nephritis of mice. The following results were obtained. (1) The ferritin particles in the GBM of animals given NF alone, as controls, were mainly restricted to the lamina rara interna (LRI) with very few penetrating the entire depth of the GBM. (2) In animals given the IC, greater numbers of ferritin particles were seen, in comparison with the control animals, not only in the lamina densa (LD) but also in the lamina rara externa (LRE). (3) Immunoelectron microscopy (IEM) demonstrated that each NF particle was accompanied by aNFab, which was found to be peroxidase positive material, throughout the GBM. (4) On the grounds that ICs were prepared in Ag great excess, it is suggested that ICs seen in the GBM are composed of a low avidity antibody with a low Ag/Ab ratio, probably Ag1Ab1. From these results, it is suggested that circulating ICs are necessary to give rise to IC deposition on the GBM and that NF and aNFab exist together as ICs throughout the GBM. We concluded that subepithelial IC deposits arise from the circulation, and that after GBM trapping, circulating small-sized IC can pass through the LD to reach the subepithelial side of GBM. PMID- 2585832 TI - [Studies on the mechanism of glomerular localization of immune complexes (2). Localization of non-dissociable immune complexes on the subepithelial side of the glomerular basement membrane]. AB - In order to investigate whether preformed (circulating) immune complexes (IC) can localize in the subepithelial side of the glomerular basement membrane (GBM), non dissociable covalently cross-linked IC (cov. IC) composed of native ferritin (NF) and anti NF antibody (aNFab) were preformed in a 2 step reaction using the bifunctional reagent, toluene-2,4-diisocyanate (TDI). Molecular weight of cov. IC was about 58 x 10(4) dalton, which suggests that the cov. IC was composed of Ag1Ab1 lattices. The GBM of mice given cov. IC intravenously showed that deposition of cov. IC was not only in the lamina rara interna but also, with time, in the lamina densa and lamina rara externa. The size of cov. IC and the distribution in the GBM described above were similar to those we studied previously using preformed dissociable NF and aNFab complexes in a 40-fold antigen great excess. From these results, we concluded that preformed immune complex in vitro can pass through the lamina densa as intact IC to give rise to the subepithelial area without dissociation or reformation. That is, the subepithelial IC deposits arise from the trapping of small-sized IC derived from the circulation. PMID- 2585833 TI - [Pathomorphological studies on arterial cushion. 2. Aminonucleoside nephrotic rat]. AB - The present study is an attempt to solve the problem of pathogenesis of focal glomerular sclerosis (FGS), especially in juxtamedullary cortex, we were investigated by measurement of luminal diameters of afferent arterioles (Aff), efferent arterioles (Eff) of numerous glomeruli, arterial cushion (AC), afferent arterioles (AC-aff) at a region of branching arteries from the interlobular arteries, using scanning electron micrographs of methyl methacrylate casts of intrarenal arteries of aminonucleoside nephrotic rats. As regards luminal diameters, Eff were nearly equal Aff in minor glomerular abnormalities (Minor). Nevertheless Eff of glomeruli with segmental sclerosis (FSHS) were smaller than Aff (t-test). AC with FSHS were smaller than ones of Minor, statistically (t test). The results of these examination, the cushion may be important factor for the regulation of blood flow in sclerotic glomeruli. PMID- 2585834 TI - [Changes in complement breakdown products and terminal complement complex in patients with acute glomerulonephritis]. AB - In this study we examined the role of the complement system in acute glomerulonephritis (AGN). Breakdown products of complements (iC3b, C4d and Bb) and Terminal complement complex (TCC, SC5b-9 complex) in plasma samples were measured by ELISA. The microassay plates were coated with monoclonal antibodies which bind specifically to human iC3b, C4d, Bb and SC5b-9 complex. This assay accurately quantitates small amounts of in vivo complement activation. The plasma samples were drawn from patients with AGN and other glomerulonephritis. There were some patients with various glomerulonephritis whose plasma iC3b, C4d and Bb concentrations were higher than those in normal human. However specificity was not found. The ratios iC3b/C3 and C4d/C4 were increased in the early stages of AGN, but plasma Bb concentrations revealed no significant changes. Plasma SC5b-9 complex concentrations were increased in the early stages of AGN. C3c, C3d, C4d and SC5b-9 were found to be localised in the glomeruli of those AGN patients. It is suggestive that in these cases of AGN (especially case 2) complement activation is predominantly mediated through the classical pathway and TCC is formed by this activation. This complement activation in the blood and the renal tissue is presumed to be involved in the initiation and progression of AGN. PMID- 2585835 TI - [IgA nephropathy in Japanese children and adults: a comparative study of clinico pathological features]. AB - A comparative clinico-pathological study was performed on 61 children and 51 adults with IgA nephropathy. Hematuria and/or proteinuria found by chance was the most common initial clinical sign, being observed in 82.0% of the children and 52.9% of the adults (p less than 0.001). At renal biopsy, hypertension and severe proteinuria were found in 9.8% and 33.3% of the adults and 0 and 14.8% of the children (p less than 0.05, p less than 0.05). Elevations of blood urea nitrogen and serum creatinine were found at the time of biopsy in 21.6% and 9.8% of the adults but in none of the children (p less than 0.001, p less than 0.05). On histological studies, proliferative changes of the glomerulus were similar in the two groups, and diffuse mesangial proliferation was found in 62.3% of the children and 51.0% of the adults (although the difference was not significant). Focal glomerulosclerosis and tubular atrophy were found in 52.9% of the adults and 32.8% of the children (p less than 0.05). These results suggest that focal glomerulosclerosis with tubular atrophy is correlated with deterioration of renal function, hypertension and age at renal biopsy, and has an important influence on the prognosis of patients with IgA nephropathy. PMID- 2585836 TI - [Uric acid metabolism in patients with chronic glomerulonephritis]. AB - Serum uric acid (SUA), creatinine clearance (Ccr), urinary excretion of uric acid (UUAV) and uric acid clearance (CUA) were determined in 357 patients with IgA nephritis (IgAN) and 81 patients with membranous nephropathy (MGN) in an attempt to clarify uric acid metabolism in patients with chronic glomerulonephritis, and UUAV/Ccr and CUA/Ccr levels were measured to investigate their correlations. As a result, hyperuricemia that could hardly be explained with a decline of Ccr alone was recognized in many cases, since the patients with hyperuricemia exceeding 7.0 mg/100 ml of SUA registered even as high as 25.5% in IgAN and 33.3% in MGN, whereas those with the Ccr levels higher than 80 ml/min registered 22.3% in IgAN and 38.0% in MGN. Although the SUA level increased and the UUAV and CUA levels decreased along with a decline of Ccr in IgAN, no similar trends were recognized in MGN. When the distribution of UUAV was studied in the patients with the Ccr levels higher than 80 ml/min, the patients whose UUAV levels higher than 800 mg/24 hrs that suggested excessive uric acid production were markedly as low as 3.9% in IgAN and 3.7% in MGN. Thus, the cause of hyperuricemia could not be attributed to an amount in the uric acid production. On the other hand, the patients whose CUA levels lower than 6.0 ml/min in the distribution of CUA that suggested a decrease of uric acid excretion registered 47.4% in IgAN and 63.0% in MGN, respectively, which equally appeared to be a type of lowered excretion in a majority of patients whose hyperuricemia was recognized in IgAN and MGN. The mechanism of the lowered excretion of uric acids from the kidney despite the normal level of Ccr has yet to be clarified. PMID- 2585837 TI - [The effects of intravenous infused magnesium on hemodynamics and renal water sodium metabolism in patients with essential hypertension]. AB - Mean arterial pressure (MAP), heart rate (HR), urine volume (UV), urinary excretion of sodium (UNaV), endogenous creatinine clearance (Ccr), fractional excretion of sodium (FENa) were measured before and after intravenous infusion of 10% magnesium sulfate (an initial dose: Mg 13.5 mg/m2.BSA/15 min; a maintenance dose: Mg 2.7 mg/m2.BSA/105 min) in 6 normotensive subjects (NT) and 12 mild-to moderate essential hypertensives (EHT). Following magnesium infusion, serum magnesium concentration (s-Mg) increased and reached the level of about 1.8 times basal value. Significant increases of UV, UNaV and FENa in both NT and EHT, and a similar tendency of Ccr in EHT were observed, while no significant change in MAP nor HR was found in the two groups. The changes in UNaV (delta UNaV) were positively correlated with those in FENa (delta FENa) and a similar tendency was shown between delta UNaV and change in Ccr (delta Ccr) in all subjects. While there was no significant percentage change of s-Mg (% delta s-Mg) nor of Ccr (% delta Ccr), those of UNaV (% delta UNaV) and FENa (% delta FENa) were significantly greater in EHT. It is concluded from these findings that magnesium infusion produces diuresis and the natriuresis which might result from suppression of renal tubular reabsorption of sodium, without any change in systemic hemodynamics in NT and EHT. The pronounced natriuretic response to magnesium in EHT might contribute to the hypotensive mechanism of magnesium loading in EHT. PMID- 2585838 TI - [Three cases presenting with systemic lupus erythematosus and minimal change nephrotic syndrome]. AB - Three cases presenting with systemic lupus erythematosus (SLE) and minimal change nephrotic syndrome (MCNS) are reported in this paper. All cases were female; they abruptly developed nephrotic syndrome at the age of 30, 11 and 23 years, respectively. In Case 1, the diagnosis of SLE was based on fever, butterfly rash, Raynaud's phenomenon, leukopenia, lymphopenia, hypocomplementemia, a high titer of anti-DNA antibodies, positive DNA and LE test, and the presence of anti nuclear antibodies (speckled pattern). In Case 2, the diagnosis was based on butterfly rash, central nervous system involvement, lymphopenia, hypocomplementemia, a positive LE cell phenomenon, a high titer of anti-DNA antibodies and a positive DNA test. In Case 3, the diagnosis was based on photosensitivity, alopecia, lymphopenia, hypocomplementemia, a high titer of anti DNA antibodies, a positive DNA test and a positive LE cell phenomenon. In these three cases, initial symptoms were puffy face and pretibial edema which occurred suddenly. These symptoms disappeared completely after either corticosteroid therapy or a combination therapy using corticosteroids and immunosuppressive drugs. These patients took a favorable course and no aggravation was noted in the findings of urinalysis and renal functions. In two of these cases, the diagnostic criteria for SLE were satisfied, but the remaining patient fulfilled only three criteria except for renal disorder. In each of these cases, minor glomerular abnormalities were disclosed by renal histology. It seems likely that SLE was complicated by MCNS in these cases. From these cases, it is suggested that there is a possibility of immunological abnormalities associated with SLE and MCNS. PMID- 2585839 TI - [Crossed "cerebral" diaschisis? Seven cases with unilateral cerebellar vascular lesion which showed decreased perfusion in the contralateral cerebral cortex]. AB - In 7 cases with unilateral cerebellar vascular lesion, decreased perfusion was observed in the contralateral cerebral cortex by single photon emission computed tomography (SPECT) with I-123 labeled N-isopropyl-p-iodoamphetamine (IMP). These cases had symptoms due to cerebellar lesions but did not show any cerebral cortical symptoms. Reduction of cerebral cortical perfusion appeared on more than 25 days after the onset of CVA, did not correlate with morphological changes by cranial X-ray computed tomography and digital subtraction angiography in acute phase, and was persistent or irreversible later. We made a guess this phenomenon was due to the remote neuronal effect through cerebellothalamic projection. PMID- 2585840 TI - [Radial long-axis tomography: a new reconstructing algorithm for thallium-201 myocardial SPECT]. AB - The long-axis (L-A) tomograms of the heart in thallium-201 SPECT have been conventionally reconstructed as those parallel to the midventricular vertical or horizontal L-A plane. We developed a new algorithm for reconstructing the rotated L-A tomograms around the L-A to longitudinally observe thallium-201 myocardial distribution and to provide an optimal view of the cardiac apex. After determining the orientation of the L-A and reconstructing the short-axis (S-A) tomograms using standard techniques, the coordinates of the S-A planes were transformed to the polar coordinates whose origin is located at the position of the L-A in each plane. Then, "radial L-A tomograms", i.e. midventricular L-A planes oriented at the angle of every 6 degrees to the midventricular horizontal L-A plane, were reconstructed. Also, we developed a new technique for analyzing thallium-201 distribution of the L-A tomograms. For the basal 2/3 regions, two profiles which consist of the pixels with maximum count on the upper and lower myocardial portions of the lines (spaced at 1 pitch) vertically to the L-A were computed. For the remaining apical 1/3 regions, the semi-circumferential maximum count profile from the values of 30 radii spaced at 6 degrees interval were computed. Based on these profiles, a 2D polar representation was then generated. From the study using a cardiac phantom with an apical small infarction, the usefulness of this new tomographic method for the detection of apical myocardial ischemia was demonstrated. The application to the exercise/redistribution studies in patients with effort angina indicated that radial long-axis tomography provides precise information about the longitudinal extent of perfusion defects, particularly in the apical regions. PMID- 2585841 TI - [Measurement of regional hepatic blood flow with 133Xe per-rectal portal scintigraphy]. AB - The hepatic blood flow (HBF) of patients with liver disease was measured by per rectal portal scintigraphy with the use of 133Xe. To analyze the time-activity curves of the liver and portal vein, washout curves of the liver were plotted, and from those, the HBF and the ratio of the HBF of the right lobe of the liver to that of the left lobe (R/L ratio) were calculated. The HBF were 143 +/- 17 ml/100 g/min in 5 patients with chronic inactive hepatitis, 119 +/- 20 ml/100 g/min in 4 patients with chronic active hepatitis, and 73.2 +/- 23.4 ml/100 g/min in 7 patients with cirrhosis of the liver. All of four patients whose HBF was under 100 ml/100 g/min and whose R/L ratio was under 1.0 had cirrhosis of the liver. Only one of the 9 patients whose HBF was over 100 ml/100 g/min and whose R/L ratio was over 1.0 had cirrhosis of the liver. The results suggested that per rectal portal scintigraphy is a useful and noninvasive method to measure the hepatic blood flow. PMID- 2585842 TI - [Exploration on the reconstruction of lung image and the estimation of lung tissue volume by single photon emission computed tomography (SPECT)]. AB - We studied the use of single photon emission computed tomography (SPECT) for evaluating lung image and measuring lung tissue volume, in a lung phantom and healthy volunteers. Three conditions of image processing were tested using the phantom, and found out a backprojection method with using a Shepp-Logan filter and a pre-reconstruction smoothing of 3 X 3 pixels to be suited. A lung tissue volume was estimated from the summation of voxels in the region where the SPECT value was greater than an arbitrary threshold level. We changed phantom lung density from 0.34 g/cm3 to 0.58 g/cm3, but there was no significant effect in the estimated volume by the density change. Changes in the lung SPECT images and lung tissue volumes in healthy subjects were studied, after changing the lung volume by applying either continuous negative body-surface pressure (CNP) to the thorax or positive end-expiratory pressure (PEEP). Difference of the lung expansion in the two methods was visualized by the SPECT images. The lung tissue volumes obtained by SPECT were correlated with the functional residual capacity by Helium dilution method (r = 0.91, p less than 0.001). We concluded that lung SPECT could be used clinically to display the distribution of a tracer radio-isotope in the lungs and also used to estimate the lung tissue volume. PMID- 2585843 TI - [Application of straight chain fatty acid analog IPPA [omega-(p-iodophenyl) pentadecanoic acid] for myocardial imaging--using acute myocardial infarction model]. AB - Application for myocardial imaging and fundamental experiments were studied using straight chain fatty acid analog IPPA [omega-(p-iodophenyl)-pentadecanoic acid]. Biodistribution of IPPA in rabbits (n = 6) shows the accumulation in liver was maintained 81.0% at 30 minutes, while the accumulations of heart, lungs and kidneys were 30.0%, 10.0% and 15.0% respectively. Especially the accumulation of heart decreased rapidly from 48.0% at 3 minutes to 30.0% at 30 minutes, reflecting the effect of beta oxidation. On the other hand, in the acute myocardial infarction mode (n = 6), with occlusion in left anterior descending coronary artery, all 6 cases showed defect images at the corresponding areas after injection of 3 mCi of IPPA. Myocardial imaging with IPPA should be useful not only for myocardial metabolic diseases (cardiomyopathy etc.) but also for ischemic heart disease. PMID- 2585844 TI - [A clinical comparison between 111In labeled leukocyte and 67Ga scintigraphy in acute and chronic inflammatory diseases]. AB - 111In labeled leukocyte scintigraphy (ILLS) and 67Ga scintigraphy (67Ga) were carried out in 56 patients (59 studies) with clinical suspicion of acute or chronic inflammation. The diagnosis of inflammation was based on cultures, autopsy findings, radiographic studies, and clinical course. The overall sensitivity and specificity to infectious foci for ILLS, considering all 80 sites studied, were 60.5%, 78.6%, and those for 67Ga were 94.7%, 47.6%. As to suppurative foci, sensitivity of ILLS and 67Ga were 95.5% and 90.9%. The duration from the onset of clinical symptoms to examination in patients with positive ILLS were significantly (p less than 0.005) shorter than in patients with negative ILLS. Also the C-reactive protein levels in patients with positive ILLS were significantly (p less than 0.05) higher than in patients with negative ILLS. Different accumulation patterns between ILLS and 67Ga were shown in 17 foci out of 21 lesions. ILLS tended to accumulate to the center of lesions strongly. On the other hand, 67Ga tended to concentrate peripherally like doughnut pattern. PMID- 2585845 TI - [Analysis of relative cerebral perfusion in ischemic cerebral diseases by single photon emission computed tomography using N-isopropyl-p-[123I]iodoamphetamine]. AB - Semiquantitative analysis of 123I-IMP SPECT enabled to evaluate relative regional cerebral perfusion and redistribution rates. Two parameters were calculated; the relative perfusion rate (RPR) is the ratio of radioactivity on a localized lesion divided by radioactivity on the visual cortex, the redistribution rate (RR) is the ratio of RPR in late images at 3 hrs divided by that in early images at 15 min postinjection. Total of 45 patients with ischemic cerebral diseases were studied. There were 29 males and 16 females with the age ranging from 37 yr to 80 yr. The RPRs were 81.3 +/- 5.1% in TIA (14 cases), 63.6 +/- 10.6% in RIND (8 cases), 64.6 +/- 8.5% in mild infarction (9 cases) and 40.2 +/- 13.8% in severe infarction (14 cases). RPR on the lesion of the severe infarction was extremely low compared to that of TIA, RIND and mild infarction. RPRs of lesions in the mild and severe infarction were reversely correlated to the size of LDA on X-ray CT (p less than 0.01). RPR was well correlated to clinical status of ischemic diseases. The RRs were 1.18 +/- 0.08 in TIA, 1.41 +/- 0.20 in RIND, 1.28 +/- 0.15 in mild infarction and 1.21 +/- 0.31 in severe infarction. The RR of RIND was significantly higher than those of other categorized groups (p less than 0.01). The RR may prove useful as a parameter reflecting tissue viability in cerebral ischemic diseases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585846 TI - [Malignant thymoma detected by thallium-201 myocardial scintigraphy]. AB - We present two cases of malignant thymoma which showed a remarkable accumulation of thallium-201 chloride on myocardial scintigraphy. A 69 year-old man underwent stress 201Tl scintigraphy to evaluate myocardial ischemia and abnormal accumulation of thallium activity was observed in the anterior mediastinum by chance. It was more clearly visualized on delayed image. Moreover, abnormal uptake of 67Ga citrate was also observed in the same region. In another 68 year old woman, there was high uptake on 201Tl scintigraphy, but no abnormal uptake using 67Ga. The diagnosis of malignant thymoma was confirmed by operation in each patient. These two cases had no abnormality in the mediastinum on the chest X-ray film and one of them had no uptake of 67Ga, 201Tl scintigraphy was more useful to detect malignant thymoma. PMID- 2585848 TI - [Basic and clinical studies on the direct assay kit for serum anti-thyroid autoantibody--I. Thyroid microsomal (peroxidase) antibody]. PMID- 2585847 TI - [The quantitative analysis of regional cerebral blood flow by peripheral venous sampling in single photon emission computed tomography using N-isopropyl-p [123I]iodoamphetamine: comparison with peripheral arterial sampling]. PMID- 2585849 TI - [Basic and clinical studies on the direct assay kit for serum anti-thyroid autoantibody--II. Thyroglobulin antibody]. PMID- 2585850 TI - [Changes in nursing technology at nursing scenes. Care at welfare facilities for the aged]. PMID- 2585851 TI - [Nursing-related activities affecting nursing technology. Nursing education- through postwar revision of the curricula]. PMID- 2585852 TI - [Nursing-related activities affecting nursing technology. Nursing research]. PMID- 2585853 TI - [Nursing-related activities affecting nursing technology. Nursing congresses and seminars]. PMID- 2585854 TI - [Nursing-related activities affecting nursing technology. Iatrogenic incidents in nursing--a review of the past incidents]. PMID- 2585855 TI - [Nursing-related activities affecting nursing technology. The standards for nursing services]. PMID- 2585856 TI - [Nursing related activities affecting nursing technology. Labor conditions (work schedules)]. PMID- 2585857 TI - [Nursing legislation--for the maintenance of the quality and quantity of the nursing profession]. PMID- 2585858 TI - [Chronological listing of the progress in nursing technology]. PMID- 2585860 TI - [Changes in postwar nursing technology. Nursing records]. PMID- 2585859 TI - [Changes in postwar nursing technology. Communication]. PMID- 2585861 TI - [Changes in postwar nursing technology. Patient observation and determination of vital signs]. PMID- 2585862 TI - [Changes in postwar nursing technology. Safety and comfort (rest)]. PMID- 2585863 TI - [Changes in postwar nursing technology. Exercises (posture and body positions)]. PMID- 2585865 TI - [Changes in postwar nursing technology. Excretion]. PMID- 2585864 TI - [Changes in postwar nursing technology. Nutrition and diet--from assistance at diet to assistance at eating]. PMID- 2585866 TI - [Changes in postwar nursing technology. Hygienic care of patients]. PMID- 2585867 TI - [Changes in postwar nursing technology. Hot or cold compresses]. PMID- 2585868 TI - [Changes in postwar nursing technology. Inhalation therapy]. PMID- 2585869 TI - [Changes in postwar nursing technology. Suction]. PMID- 2585870 TI - [Changes in postwar nursing technology. Adjustment of patient room environment]. PMID- 2585871 TI - [Change in nursing concepts affecting nursing technology. Relationship between science and nursing care technology]. PMID- 2585872 TI - [Changes in nursing concepts affecting nursing technology. Introduction of nursing plans and processes and their changes]. PMID- 2585874 TI - [Changes in nursing concepts affecting nursing technology. Understanding of the nursing objects and changes in the concept of care]. PMID- 2585873 TI - [Changes in nursing concepts affecting nursing technology. Nursing theories affecting nursing technology]. PMID- 2585875 TI - [Changes in nursing technology at nursing scenes. Hospital care: hospital wards]. PMID- 2585876 TI - [Changes in nursing technology at nursing scenes. Hospital care: ambulatory care]. PMID- 2585877 TI - [Changes in nursing technology at nursing scenes. Care at the psychiatric ward]. PMID- 2585878 TI - [Changes in nursing technology at nursing scenes. Care at emergency facilities]. PMID- 2585879 TI - [Changes in nursing technology at nursing scenes. Care at rehabilitation facilities]. PMID- 2585880 TI - [Changes in nursing technology at nursing scenes. Hospice care]. PMID- 2585881 TI - [Changes in nursing technology at nursing scenes. Continued nursing]. PMID- 2585882 TI - [Changes in nursing technology at nursing scenes. Regional nursing]. PMID- 2585883 TI - Peripheral T-cell lymphoma: clinicopathologic analyses of 25 cases. AB - Twenty-five patients with peripheral T-cell lymphoma (PTCL) were analyzed to assess clinicopathologic features of the disease and were classified according to the newly proposed histologic classification for T-cell lymphomas to study the correlation between histology and survival, if any. Histologic diagnoses were: Lennert's, 1; T-zone, 1; pleomorphic, small, 1; pleomorphic, large, 1; angiocentric, 4; pleomorphic, medium, 5; immunoblastic, 5; angioimmunoblastic, 7. Patients with PTCL were noted to be endowed with clinicopathologic factors known to adversely affect survival, such as advanced stage (92%), B symptoms (56%), liver involvement (56%), multinodal disease (52%), elevated serum LDH (48%), and so on. Response to therapy was poor. CR was obtained in 30% of patients with advanced disease with a 50% relapse rate. Median survival for the 25 patients was 13 months. No correlation was found between morphologic subtypes and survival. PMID- 2585885 TI - High cytotoxic cell activity in the marrow from patients with aplastic anemia. AB - The mechanism which produces marrow failure in idiopathic aplastic anemia is still unknown. Recent investigations have suggested the crucial role of NK cells in the regulation of normal hematopoiesis. In this study, the cytotoxic activity of mononuclear cells from human bone marrow and peripheral blood was examined against three NK-sensitive target cell lines in 15 patients with aplastic anemia as well as 21 normal subjects. Marrow mononuclear cells from aplastic anemia demonstrated a high cytotoxicity comparable to peripheral blood NK cells to these target cells. Neither large granular lymphocytes nor the cells expressing known NK cell surface phenotypes increased in aplastic marrow cell elements. The aplastic marrow cells showed strong killing activity rather than binding at single cell assay. They consisted of non-adherent and adherent cell population in plastic adherence and were unresponsive to IFN treatment. The existence of cytotoxic cells with high NK-like activity may be responsible for the mechanism of marrow failure in aplastic anemia. PMID- 2585884 TI - A clinicopathologic study of focal segmental glomerulosclerosis: comparison between nephrotic and non-nephrotic focal segmental glomerulosclerosis. AB - Seven out of 16 patients with primary focal segmental glomerulosclerosis (FGS) did not showed the nephrotic syndrome throughout their clinical courses, and then patients with FGS could be divided into the two groups, nephrotic FGS group (NS G) and non-nephrotic one (NO-G). The clinicopathologic findings of NS-G and NO-G were compared retrospectively to define the pathogenesis of the glomerular disease in FGS. No significant differences were found between the groups except for proteinuria and serum total protein or albumin, and it was impossible to distinguish the two groups only histologically. In addition, electron microscopic study revealed that the glomerular epithelial cell was altered more than the endothelial and mesangial cells in both groups, resulting in vacuolization, foot process fusion, and detachment, and the striking fact that the glomerular epithelial vacuoles consisted mainly of the dilated rough endoplasmic reticulums (RERs). The speculation is drawn that in FGS the glomerular epithelial cell is firstly damaged by unknown factor(s), manifested functionally proteinuria and/or hematuria, morphologically dilatation of RER, foot process fusion, detachment, and eventually segmental sclerosis and hyalinosis. PMID- 2585886 TI - Ischemic heart disease in systemic lupus erythematosus. A retrospective study of 65 patients treated with prednisolone. AB - We studied the frequency of ST-T changes and ischemic heart disease (IHD) in prednisolone (PSL)-treated systemic lupus erythematosus (SLE) patients and compared them with the age-matched control of rheumatoid arthritis patients not receiving PSL. Twenty-five (38%) of the 65 SLE patients revealed ST-T changes as ST elevation (4%), ST depression (36%) and T wave flattening or inversion (60%). Among the control patients 4 (10%) had T wave flattening or inversion. The frequencies of ST-T changes in patients receiving total PSL dose of up to 5g and greater than 5g were 23% and 48%, respectively. Four patients developed IHD at an unusually young age during remission of SLE while receiving low dose of PSL and 2 of them later died of myocardial infarction (MI). The latter 2 patients had received PSL pulse therapy prior to MI. Regular ECG check up for SLE patients while they are on low dose PSL or pulse therapy may help reveal early ECG abnormalities and thus detect and treat one of the major risks of long-term effects of corticosteroid therapy. PMID- 2585887 TI - A case of malignant lymphoma accompanied with arterial bleeding from the gastric lesion. AB - We experienced a case of malignant lymphoma with gastric and ileo-caecal lesions. The case was 80 year-old Japanese female with a chief complaint of anorexia. The patient had gross hematemesis on the 4th day of admission. By emergency gastroendoscopy, multiple small gastric ulcers which have sharp marginal prominences were observed. Pulsating arterial bleeding was observed and we successfully achieved hemostasis by topical injection of pure ethanol under gastroendoscopy. Biopsy specimen of that lesion showed it was malignant lymphoma. PMID- 2585888 TI - A case of massive ascites due to lupus peritonitis with a dramatic response to steroid pulse therapy. AB - A 52-year-old female patient with massive ascites due to lupus peritonitis is described. Skin biopsy specimens revealed typical features of systemic lupus erythematosus (SLE) in light microscopic and immunofluorescent examinations. Immune-complexes, antinuclear antibody and hypo-complementemia were detected in the peritoneal fluid. The massive ascites responded dramatically to steroid pulse therapy. The levels of circulating immune-complexes, anti-nuclear antibody and complement in sera were also improved after such therapy. It was suggested that steroid pulse therapy may be useful for massive ascites due to lupus peritonitis. PMID- 2585889 TI - Probucol-induced QT prolongation and torsades de pointes. AB - Probucol administration of 4 weeks produced torsades de pointes associated with exacerbated QT interval prolongation in a 36-year-old woman with Romano-Ward syndrome. With discontinuance of probucol, the QT interval corrected for rate shortened from 620 msec to 500 msec and ventricular ectopic beats disappeared completely. Although probucol is known to prolong the QT interval, associated ventricular tachyarrhythmia has not been reported in humans as yet. This case suggests that one should be very careful in the administration of probucol to patients with long baseline QT intervals. PMID- 2585890 TI - A case of Cushing's disease and multiple myeloma. AB - A 55-year-old female of Cushing's disease associated with multiple myeloma is reported. The association of the two diseases has not been previously noted. Elevated cortisol level was controlled successfully by low doses of adrenocorticolytic agent, o,p'-DDD. However, the exacerbation of multiple myeloma was found to accompany the serum cortisol normalization. Previous reports have shown the good efficacy of combination therapy with melphalan and prednisolone for multiple myeloma. It was suggested that the decrease of endogenous cortisol level might exacerbate the patient's multiple myeloma. PMID- 2585891 TI - A case of hypopituitarism and type V hyperlipidemia. AB - A 29-year-old woman developed hypopituitarism following removal of a pituitary chromophobe adenoma, and this was complicated by type V hyperlipidemia and obesity. PMID- 2585892 TI - Pituitary adenoma results in the empty sella syndrome. AB - A 69-year-old female was treated for hyperthyroidism and hypertension. In August 1984, she suddenly began suffering from polyuria and polydipsia. In October, she exhibited fever, headache, vertigo, and poor appetite, probably due to pituitary apoplexy. Her endocrine function was normal, except for partial diabetes insipidus. A contrast-enhanced CT brain scan revealed a pituitary adenoma with a ring-enhanced outer edge and a central low-density area. The MRI scan also indicated cystic adenoma. A CT scan examination repeated 6 months later showed an empty sella with a markedly decreased pituitary adenoma. This case report demonstrates that some empty sella are the final result of pituitary adenoma bleeding or infarction. PMID- 2585893 TI - Endoscopic bronchial polypectomy by high-frequency electric surgery. AB - Although polypectomy by high frequency electric surgery through the use of endoscopy has been widely applied to polypoid lesions in digestive canals, there have been very few reports of the treatment of bronchial lesions with this procedure. Recently, we have been successful in performing polypectomy without any complications using high-frequency electric surgery through a flexible bronchoscope in a patient with a benign bronchial polyp. Bronchial polypectomy by electric surgery has the advantages of preventing bleeding and providing large specimens for histological examination, compared with conventional methods, i.e. for forceps or laser methods. PMID- 2585894 TI - A case of calcitonin-producing parathyroid adenoma with primary hyperparathyroidism. AB - A 57-year-old female was admitted to our hospital with general lassitude, loss of appetite, nausea, upper abdominal pain, thirst, polydipsia and polyuria. On admission, she had an asymmetrical pear-shaped tumor in the right supraclavicular region and severe hypercalcemia. Plasma C-PTH was elevated to 22.72ng/ml. Plasma calcitonin was also elevated to 336 pg/ml. She died of respiratory and cardiac failure of two weeks after admission without any positive response to the treatment, including hemodialysis. Pathohistologically, the tumor was a parathyroid adenoma. The concentrations of C-PTH, intact PTH and calcitonin in the tumor tissue were markedly high: 4.56 micrograms/g wet, 13.9 ng/g wet and 50.7 ng/g wet, respectively. Immunohistologically, the tumor cells and the fibrous stroma were stained strongly positive to rabbit anti-human calcitonin antibody and rabbit anti-human N-PTH antibody by indirect immunoperoxidase staining. Calcitonin-producing tumors, except for medullary thyroid carcinoma are rarely reported. To our knowledge, this is the first report of such a calcitonin producing parathyroid adenoma associated with primary hyperparathyroidism. PMID- 2585895 TI - Swallowing-induced tachycardia; three modalities of autonomic nervous effects. AB - Three cases are reported who have short runs of atrial premature contractions (APCs) induced by swallowing and cough. The occurrence of the APCs were affected by autonomic nervous system in all cases. The precipitating factor is considered to be the increase of vagal tone in case 1, sympathetic tone in case 2 and both of them in case 3. The autonomic mechanism of swallowing-induced tachycardia could be divided into three categories and the treatment of these arrhythmias might be different in each group. Pharmacological autonomic blockade with atropine and propranolol is useful to reveal the underlying autonomic mechanisms. PMID- 2585897 TI - Symposium on recent trends in the research of hyperlipidemia in Japan. Presented at the 86th annual scientific session of the Japanese Society of Internal Medicine. April 2, 1989, Kyoto. PMID- 2585899 TI - [Viscoelastic properties of the alveolar wall in experimental pulmonary fibrosis]. AB - In pulmonary fibrosis the connective tissue framework and the mechanical properties of the lung are profoundly altered. Changes in amounts or distributions of each component of lung tissue (collagen, elastin, and ground substance such as glycosaminoglycans) might be expected to produce changes in viscoelastic properties of lung parenchyma and lead to mechanical inefficiency of the lungs. In order to evaluate the viscoelastic properties of the alveolar wall of fibrotic lungs, we analysed stress relaxation curves (SRL) of lung tissue in hamsters. Golden hamsters were divided into two groups: control (group C) and a group treated intratracheally with bleomycin (group B). Small piece of the alveolar wall tissue (80 x 80 x 1000 microns) was extended, and SRC was recorded for 3 minutes at the fixed extended length. Relaxation times (Tm) were used as indices of tissue viscoelastic properties. Three different Tm (Tm1: short, Tm2: moderate, and Tm3: long relaxation times) were obtained using the method of residuals. In group B, Tm3 (long relaxation time) was significantly larger than Tm3 in the other. Our results in relaxation time suggested that alveolar walls become more viscous with fibrosis. This rise in tissue viscosity with fibrosis may have been due to altered properties of the increased elastic fibers. PMID- 2585896 TI - A case of Rendu-Osler-Weber disease with cerebral hemangioma, multiple pulmonary arteriovenous fistulas and hepatic arteriovenous fistula. AB - A 46-year-old woman was admitted to the hospital because of dyspnea and palpitation. Physical examination showed severe anemia and cardiac distress. Telangiectases were found in the conjunctivas, lips and oral mucosa. Chest roentogenogram showed an enlarged cardiac silhoutte and multiple coin lesions in both lower lung fields. We diagnosed her as Rendu-Osler-Weber disease (ROW). The angiographic studies showed hemangioma in the foramen of Monro, bilateral multiple pulmonary arteriovenous fistulas, and hepatic arteriovenous fistula with a large distortion of the proper hepatic artery. Although associated vascular dysplasias have been described in patients with ROW, there is no reports on ROW in which multiple vascular abnormalities concomitantly existed such as the present case. In 163 detailed cases of ROW in Japan, the frequency of vascular lesions was summarized, and this result showed that the vascular lesions of the lung were more frequent than that of the liver or brain, in comparison with countries in Europe and America. It is very important for diagnosis and its prognosis to perform a detailed angiographic examinations and to demonstrate the precise sites of the vascular dysplasias in patients with ROW. PMID- 2585898 TI - [Radioimmunoassay of vasoactive intestinal peptide immunoreactivity in guinea pig respiratory tract]. AB - Although vasoactive intestinal peptide (VIP) has been suggested to be the neurotransmitter of non-adrenergic and non-cholinergic (NANC) inhibitory nerves, its physiological functions and movements in the airway are obscure. In this study, VIP immunoreactivity in the respiratory tract from guinea pigs was measured as a preliminary experiment to elucidate its functions. VIP immunoreactivity was measured by radioimmunoassay. The rate of VIP disappearance during extraction was 52.5 +/- 17.4 (mean +/- SD)%. The dose-response curve of tissue extract almost paralleled the standard curve of authentic VIP. VIP immunoreactivity of tracheas was 939.9 +/- 262.1 pg/g wet weight and that of extrapulmonary bronchi was 858.0 +/- 241.1 pg/g wet weight. Although VIP immunoreactivity of lung extracts was not detectable in 14 samples out of 23, the value of 9 samples was 111.7 +/- 61.5 pg/g wet weight. These results suggest that there may be more VIP immunoreactivity present in tracheas and extrapulmonary bronchi than in lungs. PMID- 2585900 TI - [Pulmonary arterial input impedance in patients with chronic pulmonary diseases]. AB - To evaluate pulmonary vascular lesions, input impedance of pulmonary arterial system was determined in 52 patients with chronic pulmonary diseases (CPD) by using a multisensor catheter. Mean values of impedance parameters in 14 subjects with normal mean arterial pressure (less than 15 mmHg) were 31 +/- 3 dyne.sec.cm 5 in characteristic impedence (Zo), 3.5 +/- 0.3 Hz in the frequency at which the first minimum of the impedance modulus occurs (fmin) and 0.85 +/- 0.3 in Zx oscillation (Zxos). In patients with CPD, Zo increased with an elevation of pulmonary arterial pressure (p less than 0.01) and fmin shifted to the right with that (p less than 0.05). These results show that stiffness of the proximal arteries in CPD is increased. In patients of interstitial fibrosis with pulmonary arterial hypertension, Zo was not significantly increased, but fmin shifted to the right. Pulse wave velocity correlated with fmin, but did not correlate with Zo. In conclusion, these results suggest that analysis of pulmonary arterial input impedance with a multisensor catheter provides useful information for patients with pulmonary hypertension. PMID- 2585901 TI - [Indomethacin inhalation therapy for patients with excessive sputum]. AB - We studied the effect of indomethacin (INDO) inhalation therapy on patients with excessive sputum due to chronic respiratory infection. INDO (3.5 x 10(-2) M) reduced sputum production from 211 +/- 43 to 106 +/- 22 ml/day (p less than 0.05, n = 7), the effect that was more remarkable in patients with diffuse panbronchiolitis (DPB). The prostaglandin E2 (PGE2) levels in sputum were also decreased significantly. In addition, to elucidate the mechanism of action of INDO on epithelial ion transport, we measured short-circuit current (Isc) of canine tracheal epithelium in response to 3 x 10(-6) M INDO under short-circuit conditions in vitro. Addition of INDO to mucosal medium decreased Isc from 42.8 +/- 6.0 to 8.2 +/- 3.5 microA/cm2 (p less than 0.01, n = 6). The increases in Isc produced by PGE2 and PGF2 alpha were abolished by furosemide, a Cl-transport blocker. These results suggest that INDO inhalation is a promising therapy in improving excessive sputum production, and that this effect may be attributed to inhibition of PGE2-dependent Cl-secretion into the airway lumen. PMID- 2585902 TI - [CT findings of post-pneumonectomy patients]. AB - CT findings following pneumonectomy were studied in 28 cases with lung cancer. A total of 53 CT images were evaluated in 13 right pneumonectomy cases and 15 left pneumonectomy patients. The postpneumonectomy pleural space (PS), thoracic space of the operated site (TS) and the thoracic space of the non-operated site (CTS) were measured at 3 slice levels of the brachiocephalic level, subcarinal level and lower pulmonary vein level, using a digital planimeter. There was no significant difference in the TS/CTS ratio, between the right pneumonectomy group and the left pneumonectomy group, but the PS/TS ratio in the left pneumonectomy group was smaller than that in the right pneumonectomy group (p less than 0.01). The PS/TS ratio in both groups and the TS/CTS ratio in the right pneumonectomy group were decreased with time. In the left pneumonectomy group, the TS/CTS ratio was greater in the median sternotomy group that of the posterolateral thoracotomy group (p less than 0.01). Residual pleural effusion was accompanied with a thin circulating lesion along the outer surface. This lesion had been reported as thickening of the parietal pleura, but it could be detected in the case of panpleuropneumonectomized state. Additionally, in some cases, the parietal pleural imaging could be separated from the circulating lesion. So, this structure was thought to be mainly composed of organized effusion. CT images could detect some parts of the episodes in post operated thorax, because of the lack of the information with the sagittal direction. However, the recognition of the common changes and images on CT after the operation might be helpful for the follow-up of the patients. PMID- 2585903 TI - [Comparison of high resolution computed tomography and pulmonary function tests in diagnosis of mild emphysema]. AB - To assess the ability of high resolution CT scan and pulmonary function tests in detecting and grading mild emphysema, we correlated the high resolution CT scan and pulmonary function tests with the pathologic grade of emphysema and the destructive index of lung specimens from 42 patients undergoing thoracotomy for solitary pulmonary nodules. Using the high resolution CT scan, we could identify the pathologic grade of mild and moderate emphysema. By measuring diffusing capacity per unit alveolar gas volume (DLco/VA), it seemed to be possible to detect the mildest degree of alveolar destruction assessed by the destructive index, which was not detected by high resolution CT scan. The reason for these results seemed to be that we assessed the severity of emphysema by detecting the air space enlargement on high resolution CT scan images caused by the destruction of alveolar walls, which were detectable by measuring DLco/VA. We conclude that it is possible to detect mild emphysema using the combination of high resolution CT scan and pulmonary function tests. PMID- 2585905 TI - [A case of thymic cyst with elevated CEA in the cystic fluid]. AB - A 66 year-old male was admitted on October 31, 1987 because his chest X-ray film revealed a well-defined round shadow in the right inferior mediastinum. Chest CT showed a large homogenous mass in the right anterior mediastinum. The mass was identified as a cyst on echogram. Surgical removal of the cyst was done with right thoracotomy. The cyst was 15 cm in size and contained about 500 ml of grayish white fluid. Pathological examination showed a thymic cyst and no malignancy. Biochemical analysis of the cystic fluid revealed increased CEA value of 223.2 ng/dl in spite of normal CEA level in serum. CEA was demonstrated in the epithelium of the surface and Hassall's corpuscles by PAP stain. It is conceivable that this elevated CEA observed in the cystic fluid might be correlated with CEA-like antigens such as NCA, NFA and BGP. PMID- 2585904 TI - [Six cases of HTLV-I associated bronchiolo-alveolar disorder (HABA)]. AB - A new clinicopathological state related to HTLV-I infection was found in patients with diffuse panbronchiolitis (DPB) and idiopathic interstitial pneumonia (IIP). This specific state with chronic and progressive respiratory symptoms caused by bronchiolar or alveolar disorder was characterized by smoldering adult T-cell leukemia or the HTLV-I carrier state known as HTLV-I associated bronchiolo alveolar disorder (HABA). The clinical features of 5 cases with the bronchiolar type of HABA and one case with alveolar type of HABA were described and were compatible with the criteria of DPB and IIP, respectively. Long-term subclinical infection of HTLV-I was suspected to play an important role in the pathogenesis of HABA. Furthermore, the investigation of HABA might yield a clue to the unknown etiology of DPB and IIP. PMID- 2585906 TI - [A case of adult Still's disease with severe pulmonary complications]. AB - We reported a case of adult Still's disease accompanied by pericarditis, pleuritis and extensive pneumonitis with respiratory failure. A 59-year-old woman was admitted to our hospital because of high grade fever and sore throat. She had a spiking fever between 38 degrees C and 40 degrees C. Surface lymph nodes were palpable in the neck and inguinal lesions and hepatosplenomegaly was recognized. Laboratory data showed a marked increase in peripheral leukocytes, erythrocyte sedimentation rate, liver dysfunction and anemia. Serologic tests were negative for various autoantibodies and rheumatoid factor. She received various antibiotics, but there was no improvement. Later, a rheumatoid rash which suggested adult Still's disease developed. The diagnosis of adult Still's disease was made by skin biopsy and clinical course. Although pericarditis, pleuritis and extensive pneumonitis were accompanied with severe respiratory failure, her symptoms improved with steroid pulse-therapy. A transbronchial lung biopsy revealed moderate fibrosis and cell infiltration in alveoli. PMID- 2585907 TI - [A case of malignant pleural mesothelioma with infectious bronchogenic cyst]. AB - A 47-year-old man was admitted with a cough on January 4, 1986. A chest X-ray film showed a mass shadow in the left lower lung, which was revealed to be a bronchogenic cyst by CT scanning and ultrasonography. Thoracotomy was performed on March 3, 1986 because cytologic tests on the fluid in the cyst suggested malignancy. A cyst, two tumors on the diaphragm and pleural thickening were revealed. Microscopic examination showed a benign bronchogenic cyst and a mixed type malignant mesothelioma. In spite of chemotherapy (ADR, Cis-DPP, 5 fluorouracil) and immunotherapy (OK-432, PSK), the pleural thickening progressed, as was demonstrated by CT scanning and ultrasonography. Although cardiac tamponade due to invasion by the malignant mesothelioma developed, this was improved by cardiocentesis. The patient died of pneumonia on March 28, 1987. We studied the concentration of mineral fibers in lung and tumor tissues of this case by Energy Dispersive X-ray Analyser because asbestos or non-asbestos inorganic fibers might cause malignant mesothelioma. This case of malignant pleural mesothelioma accompanied by a bronchogenic cyst is very rare. PMID- 2585908 TI - [A case of pulmonary lymphangiomyomatosis induced by pregnancy]. AB - A 35-year-old primigravida was admitted to the Department of obstetrics complaining of dyspnea and left back pain at 21 weeks' gestation. Chest roentgenogram revealed diffuse reticulonodular shadows predominantly in both lower lung fields and arterial hypoxemia was present. Pulmonary function tests showed restrictive impairment and decreased carbon monoxide diffuse capacity. From these results, interstitial pneumonia was suspected and she was first treated with prednisolone. However during her pregnancy, spontaneous pneumothorax occurred. Following spontaneous delivery of healthy infant at 37 weeks, left chylothorax occurred, and pleurodesis was performed with OK432. Thereafter the histological diagnosis of pulmonary lymphangiomyomatosis was made by transbronchial lung biopsy and treatment of prednisolone was stopped. She was treated with tamoxifen. In addition, progesterone-receptor was detected in the pulmonary tissue obtained at open lung biopsy. She was treated with cyclophosphamide in addition to tamoxifen. At present, shortness of breath has decreased slightly in comparison with one year previously, but no improvement has been seen in lung function tests or chest roentgenogram. PMID- 2585909 TI - [Diurnal changes in colonic motility in conscious dogs]. AB - Daily profile of colonic motor activity was observed in 10 conscious dogs by means of extraluminal force transducers. Each dog was implanted with a set of seven strain, gauges, one on the terminal ileum and the remaining six on the colon equidistantly. The colonic motor activity was basically composed of migrating and non-migrating motor complexes at all six recording sites. Each motor complex was characterized by a tonic contraction superimposed by rhythmic bursts of phasic contractions. During fasted period these motor complexes recurred at a mean interval of 36 min, and a mean duration was 7 to 12 min. Those motor complexes which migrated over at least three recording sites were defined as "migrating", 72% of those observed at the most proximal sites (n = 2680) were migrating, and the remaining 28% were non-migrating. Of those migrating motor complexes 90.4% migrated caudad (iso-peristalsis), while only 9.4% migrated orad (antiperistalsis). During postprandial period the colonic motor complexes at all recording sites uniformly increased their frequency with shorter intervals. Different from the small intestine, the contractile patterns were essentially the same as those of fasted period. The postprandial acceleration of the colonic motor complexes seems to be compatible with gastrocolic response. PMID- 2585910 TI - [Percutaneous recording of gastric electrical activity (electrogastrography): its technique and analysis]. AB - In 1922, Alvarez made some electrical recordings from cutaneous electrodes, but the method has not been widely adopted. It has been caused by the technical difficulties in recording, and in extracting consistent information from the recording. Therefore in an effort to improve the ability to routinely obtain a recording of the gastric electrical activity, using cutaneous electrodes (electrogastrography, EGG), we have investigated different electrodes placement and bipolar recording techniques. We studied 10 healthy asymptomatic volunteers. Frequency and power product have been used to help interpret the potential change. We found significant frequency component at approximately 3 cycle/min. Recordings from the upper part of epigastrium were better than those from the lower part of epigastrium. This suggests that these recordings are taken from electrical activity of the stomach. We found the good placement of cutaneous electrodes and good recording techniques. PMID- 2585911 TI - [Cremasteric reflex. Its application to urological diagnosis]. AB - Responses to electrically evoked cremasteric reflex with bulbocavernous reflex and cystometrogram were observed on 55 male adults who have complaints of micturition or sexual disorders. As the reflex centers for these reflexes were localized in the lower spinal segments, the observed results were used for the estimation of the injured loci in combination with clinical symptoms. The cremasteric reflex which was dealt with in this paper was the cremasteric EMG responses evoked by single electric shock applied to the ventromedial surface of the thigh or to the dorsum of the penis. The stimuli used have usually tenfold intensity of the sensory threshold, having 0.2 msec duration. The EMG recording was made with a coaxial needle electrode inserted into the ipsilateral cremasteric muscle at the level of the pubic bone. All 20 controls without neurological disorders showed positive cremasteric responses, and the normal range of the latency and the burst length were 68-77 msec and 52-59 msec, respectively, in case of thigh stimulation. More than half of the patients suffered from the disorders of neural origins showed no reflex even for stronger stimulation. Combining with these data, the diagnostic usefulness for the localization of injuries in patients having disorders in either spinal cord or in cerebral vessels was positive. Cerebral influence to the cremasteric reflex was deduced to be a potentiating factor to elongate the burst duration for stronger stimuli. Further detailed observations would yield useful clues for neuro urological diagnosis of the lower spinal cord injuries. PMID- 2585912 TI - [Recurrence and prognosis of renal pelvic and ureteral carcinoma]. AB - Eighty-three patients with renal pelvic and ureteral carcinoma operated in Chiba University Hospital were followed. Age ranged between 23 and 79 years old (average 61.8 years) with the male-to-female ratio of approximately 2:1. Localization of tumors was in renal pelvis in 41 (49.4%), ureter in 29 (34.9%) and both in 13 (15.7%). Significant correlation in prognosis was obtained with macroscopic hematuria, histological classification, grade, stage and regional lymph node involvement. Recurrence was found on 49 cases (59%), 21 had intra vesical tumor and 28 showed retroperitoneal recurrence or distant metastasis. In the former the mean tumor free interval was 14.8 months and 5 year survival rate was 62.1%. In the later the mean tumor free interval was 6.5 months and 3 year survival rate was 5%. 8 (38.1%) in 21 cases with low stage papillary transitional cell carcinoma showed recurrence and it was all intra-vesical tumor. 25 (56.8%) in 44 cases with high stage papillary transitional cell carcinoma showed recurrence. Retroperitoneal recurrence or distant metastasis was recognized in 12 cases. On the other hand 14 (87.5%) in 16 cases with non-papillary transitional cell carcinoma showed recurrence, which was all retroperitoneal recurrence or distant metastasis. PMID- 2585913 TI - [Clinical study of a modified Stamey's endoscopic bladder neck suspension procedure for one hundred female patients with stress incontinence]. AB - One hundred female patients with stress incontinence have been operated on by means of modified stamey's endoscopic bladder neck suspension procedure, i.e. quantifying the thread tension for bladder neck suspension. Twelve patients had 1,000 grams in the nylon loop, 5,800 grams, 9,700 grams, 25,600 grams and 49,400 grams. A follow-up period varied from 10 to 32 months (mean: 20.5 months). A 60 min pad-weighing test revealed urinary loss of 1.0 to 196.0 grams/hour (mean: 36.0) prior to operation. 1. The modified Stamey's procedure was successful in 95 patients (95%). The appropriate thread tension for bladder neck suspension was 400 grams. 2. Various complications were encountered: removal of unilateral nylon suture was necessitated in 2 patients, bleeding from operative wound in 2, bladder tamponade in 2, and clean intermittent catheterization for more than one month in 4. 3. Micturition parameters, i.e. maximum and average flow rates, temporarily got worse post-operatively. Maximum urethral closure pressure decreased and functional profile length elongated which were significantly different from those of pre-operative values. 4. Questionnaire sent to the patients revealed that 89 percent of them were satisfied with the operative results but 11 percent were not. 5. The modified Stamey's procedure is simple to perform and prevents over-tightness of nylon loops. We conclude that this operative method is the treatment of choice for correction of stress incontinence. PMID- 2585915 TI - [Factors influencing the recurrence rate and metastatic rate of bladder cancer]. AB - Preservation surgeries have been applied for cancer of the urinary bladder in 202 cases during the past twenty years. We herein report the result of a statistical analysis on the background factors which determine the tumor recurrence rates and metastatic rates. The background factors analysed were as follows: size of tumors, number of tumors, histological staging, grading, lymph vessel permeation (ly) and vessel invasion (v). Each factor was analysed by Kaplan-Meier method and multiple regression analysis. By Kaplan-Meier method, tumor size, stage, grade, ly and v were closely related to the tumor recurrence and metastasis. By multiple regression analysis, tumor size, stage and ly were important for recurrence, while tumor size, stage and v were important for metastasis. In this study, histological grading was not so closely related to tumor recurrence and metastasis. PMID- 2585914 TI - [Guideline of surgical treatment of prostatic adenocarcinoma]. AB - Based on study of 274 cases of prostate cancer treated in our clinic, selection of patient for radical surgical treatment and choice of procedures were discussed. The radical surgical procedures experienced in our clinic were classified as 31 cases of radical prostatectomy, 4 cases of radical cystoprostatectomy and 7 cases of pelvic exenteration. The endocrine therapy was added to non curative cases postoperatively. In the radical prostatectomy group, the 5-year survival rate of patients with stage A and stage B prostatic adenocarcinoma were 100 and 93 per cent, respectively, and 5-year survival rate of patients who had stage C prostatic adenocarcinoma was 75 per cent. The 5-year survival rates of patients with stage C prostatic adenocarcinoma treated by radical cystoprostatectomy and pelvic exenteration were 50 per cent and 66 per cent, respectively. Cancer recurrence has not seen in the bladder in the patients with stage C prostatic adenocarcinoma treated by radical prostatectomy. Operation of urinary diversion had improved the quality of life. From this data, radical prostatectomy would be indicated for the treatment of patients with stage A, stage B and stage C prostatic adenocarcinoma. PMID- 2585916 TI - [Influence of protein intake on phytohemagglutinin skin test in patients undergoing maintenance hemodialysis]. AB - We studied the influence of protein intake on the phytohemagglutinin (PHA) skin test and purified protein derivative (PPD) skin test in 45 patients on maintenance hemodialysis. The patients were 23 males and 22 females, the ages ranging from 19 to 80 years, with an average of 53.6 years. All patients were being maintained on long-term hemodialysis (mean 37.3 months). They were divided into three groups according to protein intake: Group A; less than 1.1 g/kg/day, Group B; 1.1-1.5 g/kg/day, Group C; more than 1.5 g/kg/day. There were no significant differences among the three groups with respect to age, causative disease and the period of maintenance hemodialysis. We measured protein intake, PHA skin test and PPD skin test. Significant differences were found between Group B and Group C with respect to the PHA skin test values and PPD skin test values, the values of Group C being very low compared with those of Group B. The PHA skin test values and PPD skin test values were only slightly lower in Group A than in Group B. The negative reaction rate of PPD in Group A and Group C was much higher than in Group B. The results suggest that excess intake of protein impaired cellular immunity in maintenance hemodialysis patients, and that protein deficiency can also have a detrimental effect on cellular immunity. Therefore, adequate protein intake should be maintained for optimizing cellular immunity. PMID- 2585917 TI - [Renal dysfunction in children with vesicoureteral reflux]. AB - It is well recognized that reflux nephropathy is one of the commonest causes of end-stage renal failure (ESRF) in children. We made a retrospective study of 28 children with vesicoureteral reflux (VUR) who showed impaired renal function, as defined by either the serum creatinine of more than 1.0 mg/dl or BUN of more than 20 mg/dl. There were 20 boys and 8 girls, and the incidence of both sexes was 4.8% and 1.9% respectively. Of patients, proteinuria was detected in 22, and hypertension in 7. Five patients progressed to ESRF during his or her clinical course. About half of the patients in this series presented proteinuria or growth retardation which had led to urological check-up. Bilateral reflux was demonstrated in 24 patients, and all of the remaining 4 with unilateral reflux had hypoplastic or dysplastic contralateral kidney. Micturition cystourethrography revealed moderate or severe reflux in 86% of the ureters either at the first examination or during the follow-up periods. Urographic findings which suggested renal dysfunction included bilateral small kidney, unilateral small kidney with contralateral renal scarring, and bilateral generalized renal scarring. According to the pattern of the progression of renal dysfunction, patients were subdivided into 3 groups. Group I; patients showed bilateral renal hypoplasia on urography, and renal dysfunction progressed to ESRF before the age of 10 years despite surgical treatment. In patients of group II, gradual decrease of renal function led to ESRF at the age of puberty, although SCr was around 1.2-1.5 mg/dl when they were about 10 years old. In group III, renal function was stable at about 1.0 mg/dl of SCr during childhood. Temporary improvement of renal function was observed in only 3 of 21 children who were followed for more than 1 year after antireflux surgery. Deterioration of renal function was caused within 6 months to one year. Antireflux surgery had only little influence on the improvement of renal function in this series. We emphasize the need for early detection and management of reflux to prevent progression of renal dysfunction. PMID- 2585918 TI - [Analysis of the urinary risk factors of urolithiasis in healthy children]. AB - Since incidence of idiopathic calcium oxalate urolithiasis in children was very low, a study was made to analyze the risk factors of calcium oxalate stone in male volunteers without any episode of urolithiasis. They were divided into four groups, group I: eight years old, group II: 11 years old, group III: 18 to 24 years old, group IV: 41 to 45 years old. Inhibitory activities of urine were significantly higher in groups of children than in groups of adults. However, inhibitory activities of filtered urine, extracted through filters with conserved limit of 25000 of molecular weight, were reduced significantly. Therefore, it was suggested that materials with molecular weight over 25000 participated in the inhibitory activities. Furthermore, the activities of filtered urine of group I were still higher than those of the non-filtered urine in groups of adults. Accordingly it was considered that substances less than 25000 of molecular weight also participated in the inhibitory activities in children. An analysis of uric acid, citrate, magnesium and uronic acid in urine revealed that magnesium excretion volume and magnesium concentration ratio to creatinine were higher in children than in adults. Magnesium seemed to boost the inhibitory activities in children. In the measurement of crystalloid materials, the concentration of calcium was significantly lower in children groups than in groups of adults. It seemed that calcium also takes part in reduction of incidence of urinary stone in children. PMID- 2585919 TI - [Chemosensitivity testing on human bladder cancer cell lines, using MTT-assay]. AB - Sensitivity of human transitional cancer cells to anticancer agents was evaluated utilizing cultured cell lines. T-24, MGH-U1 and KU-1. Simultaneously, chemosensitivity tests combined with 42 degrees C hyperthermia were performed. Cells inoculated in 96-well multiplates for 48 hours, were exposed to graded concentrations of doxorubicin (DOX), mitomycin C (MMC), bleomycin (BLM), peplomycin (PEP), cis-diamminedichloroplatinum (II) (CDDP) for 2 to 48 hours. After additional culture for 48 hours, viable cell numbers were estimated by the dye exclusion assay (DEA) and tetrazolium-based colorimetric assay (MTT-assay). In 2-hour exposure, most of anti-cancer agents did not significantly suppress the growth of the cell lines. Only DOX suppressed the cell growth. In 6-hour and 48 hour exposure, DOX, MMC and CDDP showed significant growth inhibitory effect on the transitional cancer cell lines. The effect of BLM and PEP was insufficient. The hyperthermia of 42 degrees C enhanced the growth inhibitory effect of MMC and CDDP, but did not influence the effect of DOX. In comparison of DEA and MTT assay, viable cell numbers measured by DEA well correlated with the optical density in MTT-assay. Since MTT-assay is a semiautomated, rapid and inexpensive assay with good reproducibility, it can be a useful substitute for DEA in chemosensitivity testing of cancer cells. PMID- 2585920 TI - [Translumbar radical nephrectomy of renal cell carcinoma]. AB - We invented a new surgical approach to the kidney through the flank to perform a radical nephrectomy for renal cell carcinoma. With the patient in usual lateral decubitus position keeping the dorsum vertical to the operating table, a skin incision is made over the XII rib from the posterior axillary line to the lateral edge of the rectus muscle. After the tip of XII rib is resected by about 5 cm, the retroperitoneal space is entered. Blunt dissection of the posterior aspect of Gerota's fascia from fasciae of the quadratus lumborum and psoas muscle is easily carried out with a liver retractor or intestinal spatula. The pulsating renal artery can be identified through Gerota's fascia when the renal hilus is exposed. Following ligation and division of the artery, renal vein is exposed. On the left side, adrenal, gonadal and occasionally lumbar veins are also ligated and severed in addition to the renal vein. Then, the kidney in Gerota's fascia is removed en bloc with perinephric adipose tissue and adrenal gland. Of 21 patients with renal cell carcinoma seen during 1 year and 3 months from June 1987, 11 underwent this operation, and other 10 patients transperitoneal radical nephrectomy because of the possible tumor extension into the renal vein, inferior vena cava or adjacent organ, the severe spinal deformity or metastases and the necessity of additional surgical procedures for concomitant benign intraperitoneal diseases. The blood loss was smaller and operating time was shorter significantly in the translumbar group than the evaluable transperitoneal group. None of those in the translumbar group received blood transfusion. As complications, pneumothorax due to pleural injury during operation and postoperative incisional hernia occurred each in one patient, but no other serious one was found. From the above results, this approach seems to be one of choices for the surgical treatment of renal cell carcinoma, as long as the tumor is not likely to extend to adjacent organs, ipsilateral nodes or the inferior vena cava. PMID- 2585921 TI - [Clinical experience with Ureteromat in transurethral ureterorenoscopy]. AB - By September 1988, we performed 58 ureterorenoscopies (52 for primary ureteral calculi, 3 for ureteral biopsy, 2 for ureteral stricture and 1 for ureteral foreign body) using a Ureteromat (Uromat Storz, West Germany). Continuous saline irrigation with the Ureteromat has obviated mechanical dilation of the ureteral orifice in 93.1% of the cases, which made this endoscopy as easy as the conventional cystourethroscopy. In 4 cases (6.9%), however, balloon dilation of the ureteral orifice was necessary for the passage of a rigid ureterorenoscope. Of 52 ureteral calculi, 37 were assigned for transurethral ureterolithotripsy (TUL), whereas transurethral ureterorenoscopy (TUURS) was indicated to flush the remaining 15 calculi up into renal pelvis for later extracorporeal shock wave lithotripsy. TUL was successful in 81.1% (30/37). The causes of failure were stone migration in 6 cases and ureteral avulsion by electrohydraulic lithotripsy necessitating open surgery in 1 case. The irrigation with the Ureteromat facilitated the manipulation of intraluminal ureteral lesions always under clear vision; by-passing the impacted stone with a guide wire and flushing-up of the calculi were successfully performed in 100%, in spite of the co-existing edematous and inflammatory mucosal changes. In 7 cases where ureteroscope could not be advanced well up to the lesion because of spasm in the iliac ureter, the irrigation pressure was transiently increased up to 200 mmHg to allow safe and easy dislodgement of impacted calculi under fluoroscopic guidance. This procedure was also effective to introduced a ureteral stent over a guide wire in 2 cases of ureteral stricture, which could not be achieved by conventional cystoscopic procedure. Immediate postoperative complications were fever in 8.6% and gross hematuria lasting for more than 4 days in 8.6%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585922 TI - [Studies on biological characteristics of transitional cell carcinoma of the bladder in patients under 30 years of age]. AB - The incidence of transitional cell carcinoma (TCC) of the bladder has been increasing in men with a peak incidence occurring in the sixth decade. However, development of tumors under the age of 30 is relatively rare. In this regard, it has been reported that vesical tumors in the young group is less malignant and rare to recur when compared with those in the elderly group. Recently, flow cytometric DNA histograms (FCM) provides quantitative and objective informations for detection and evaluation of malignant potential of bladder neoplasms. Here we report patients with tumor of the bladder under 30 years old and assess the clinical properties and biological characteristics of their tumors based on FCM. A total of 11 patients from 1975 through 1988 were reviewed. Their mean age at the diagnosis was 22.6 years old (range from 22 to 29 years old). Male/female ratio was 2.7:1. The mean follow-up period was 4 years and 7 months (range from 8 months to over 13 years). An asymptomatic gross hematuria was found in all of the patients, which is the most common sign. Filling defects of the bladder on excretory urograms were observed in six out of the 11 patients (54.5%). Cystoscopically, the size of tumors was less than 2 cm in diameter. Ten patients had a single tumor and one patient had multiple tumors at the time of the initial diagnosis. Endoscopically tumors were papillary in all but one patient, who had a non-papillary tumor. Their urine cytology showed class I in one, class II in eight, class III in one, class IV in one and class V in none.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2585924 TI - Origin of mullerian duct and its later development in relation to Wolffian duct and anogenital distance in the rat. AB - On day 14 of fetal life in the rat, Mullerian (paramesonephric) duct in both sexes was first observed close to Wolffian (mesonephric) duct. Its caudal end joined Wolffian duct at about the level of the middle of gonadal anlage. Thereafter, Mullerian duct became independent of Wolffian duct through its whole length. Therefore, the main part of Mullerian duct may be formed by budding from Wolffian duct. On day 16, the anogenital distance in male started to increase with thickening of Wolffian duct and disappearance of Mullerian duct. Castration of male fetuses on day 19 stopped later masculinizing development. Therefore, it is clear that the fetal testis is an organ crucial for the masculinization of the urogenital tract as it activates the secretion of masculinizing hormone(s). PMID- 2585923 TI - Comparative studies on the binding specificities of pertussis toxin and different lectins to human erythrocytes. AB - The binding specificity of pertussis toxin (PT) was compared with lectins with well-defined specificities by hemagglutination, hemagglutination inhibition and competitive binding assays. Neuraminidase-treated human erythrocytes were much less weakly agglutinated by PT than untreated ones. Hemagglutination of untreated human type A erythrocytes by PT was inhibited by fetuin, haptoglobulin and hog A + H. Mono- and disaccharides, and N-acetylneuraminic acid alone were ineffective at the highest concentrations used. On the other hand, hemagglutination by Ricinus communis agglutinin (RCA-1) was effectively inhibited by these substances. Similar results were also obtained in competitive binding assays with 123I-labeled PT and untreated type A erythrocytes. The binding of 125I-labeled PT to type A erythrocytes was not effectively inhibited by any of lectins with well defined specificities. These results suggest that the combining site of PT may be specific for terminal sialic acid and/or sialic acid-linked carbohydrate portion(s) which can not be recognized by lectins reported previously. PMID- 2585925 TI - Clinical studies on canine dirofilarial hemoglobinuria: measured and calculated serum osmolalities and osmolar gap. AB - Serum osmolalities and osmolar gap were determined in 43 normal healthy beagles (control group) and 40 dogs with dirofilarial hemoglobinuria (hemoglobinuria group). In the control group, the measured and calculated serum osmolality levels were in the means of 296 +/- 5 (SD) mOsm/kg and 293 +/- 6 mOsm/kg respectively, showing an osmolar gap less than 10 mOsm/kg. In the hemoglobinuria group, the measured serum osmolality ranged from 272 to 370 mOsm/kg. A considerable number of dogs had normal serum osmolalities in spite of severe intravascular hemolysis, suggesting that the changes in serum osmolality would not be the direct cause of intravascular hemolysis. The measured serum osmolality (331 +/- 28 mOsm/kg) was significantly higher in 11 dogs which died after a surgical removal heartworms than in 29 dogs which recovered after the removal (302 +/- 17 mOsm/kg). The calculated serum osmolality level was 296 +/- 16 mOsm/kg in 24 recovered cases, and 304 +/- 22 mOsm/kg in 10 fatal cases. The osmolar gap stayed in the normal ranges of 5.4 +/- 5.9 mOsm/kg in recovered cases, but it attained a higher level of 22.7 +/- 8.9 mOsm/kg in fatal cases, suggesting poor prognosis in cases with large osmolar gaps. There were significant positive correlations between the measured serum osmolality and osmolar gap, serum sodium, potassium, BUN, GOT, GPT, creatinine, bilirubin and plasma hemoglobin values, as well as between the osmolar gap and serum potassium, BUN, GOT, GPT, creatinine and bilirubin values. The plasma hemoglobin concentration fell markedly without significant change in serum osmolality 20 hr after the heartworm removal. PMID- 2585926 TI - Prevention of adverse reactions following milbemycin D administration to microfilaremic dogs infected with Dirofilaria immitis. AB - Some adverse reactions such as shock-like reaction and dirofilarial hemoglobinuria (caval syndrome) occasionally occurred in microfilaremic dogs following milbemycin D (Milbe) administration. This study was carried out to seek the prevention of these adverse reactions. In two groups containing 16 and 9 dogs respectively which were administered either chlorpheniramine maleate (1 mg/kg) or indomethacin (2.5 mg/kg) simultaneously with Milbe (1 mg/kg), the incidence of clinical signs such as the pale color of the visible mucous membranes, respiratory disorders, caval syndrome and shock-like reaction as well as changes in clinical parameters such as RBC and WBC counts, WBC profile and serum total protein, were almost equal to that observed in the group administered Milbe alone. In 41 dogs administered prednisolone (1 mg/kg) simultaneously with Milbe (1 mg/kg), no shock-like reaction was observed. Changes in clinical parameters were different from those in the group administered Milbe alone, whereas some clinical signs of adverse reactions, including caval syndrome, were observed. These results indicated that prednisolone was effective for prevention of the shock-like reaction in microfilaremic dogs induced by Milbe. PMID- 2585927 TI - Isolation and characterization of C-reactive protein and serum amyloid P component from bovine serum. AB - C-reactive protein (CRP) and serum amyloid P component (SAP), which are known as acute phase reactants in human and many other animals, were purified from cow sera. Affinity chromatography using HE agarose gel was the most effective method to isolate both CRP and SAP from a large volume of bovine serum. Separation of CRP and SAP from the mixed preparation could be performed by DEAE-cellulose column chromatography, gel permeation HPLC using TSK-G3000SW or affinity chromatography using phosphorylcholine derivatives of bovine serum albumin conjugated Toyopearl HW 65. Bovine CRP and SAP were identified as genuine CRP- and SAP-class proteins by their cross reactivities with anti-human CRP and anti human SAP, respectively, and by their homology in amino acid compositions compared with those of human CRP and SAP, respectively. Bovine CRP moved slower than beta-globulin, and bovine SAP moved in the beta-globulin region in agarose gel electrophoresis. Both of them gave single bands in native polyacrylamide gel electrophoresis (PAGE). Bovine CRP and SAP molecular weights were estimated to be 100,600 and 109,500 daltons respectively, by sedimentation equilibrium analysis. Bovine CRP showed 23K dalton subunits by sodium laurylsulfate-PAGE and bovine SAP showed 28K and 32K dalton subunits, both of which were glycosylated and had identical amino acid compositions, indicating that both CRP and SAP molecules are pentamers. In fact, they appeared to have pentameric disk-like configurations in electronmicroscopical examination. PMID- 2585928 TI - Lactate dehydrogenase isoenzyme patterns in bovine liver tissue. AB - Liver lactate dehydrogenase (LDH) isoenzymes in normal and diseased cows were analyzed electrophoretically. This method (histoelectrophoresis) was improved for the direct analysis of tissue LDH isoenzymes. The mean values of LDH 1 through LDH 5 in the livers of normal cows were 31.7, 24.8, 27.3, 12.8, and 3.3%, respectively. In cases with hydropic degeneration of the liver, the patterns revealed increases of LDH 1 and LDH 2 as compared to normal cows. The patterns showed a decrease of LDH 1 and an increase of LDH 2 in fatty change of the liver. Congestion of the liver alone decreased LDH 1 and increased LDH 3, LDH 4 and LDH 5. Necrosis of the liver decreased LDH 1 and LDH 2, and increased LDH 3, LDH 4 and LDH 5. It was suggested that the functional hepatocellular damage due to anoxia might be a important factor of the change of liver LDH isoenzyme patterns. We have attempted to standardize the LDH isoenzyme patterns by using a computer under various conditions. In cases with hydropic lesions, the diagnostic sensitivity (DS) was 53% (28 of 53 cases) and the predictive value of positive tests (PVPT) was 100% (28 cases of 28 cases selected). In cases with congestive or necrotic lesions, DS was 41% (9 of 22 cases) and PVPT was 69% (9 cases of 13 cases selected). PMID- 2585929 TI - Studies on serum tocopherol, selenium levels and blood glutathione peroxidase activities in calves with white muscle disease. AB - For the purpose of clarifying the cause of white muscle disease (WMD) in calves, tocopherol and selenium levels and blood glutathione peroxidase (GSH-Px) activity were measured on 10 calves with WMD and nine of their dams. The main clinical symptoms of the 10 calves with WMD were motor disturbances including recumbency and stiffness. Serum enzyme activities (GOT, GPT, CPK, LDH) in calves with WMD increased markedly, and this increase was also observed in some of their dams. Serum tocopherol levels of calves with WMD were low, 70% of which showing deficient levels of less than 70 micrograms/100 ml. Serum selenium levels of all the calves were lower than 35 ppb, indicating a deficiency, and were accompanied by low blood GSH-Px activity. alpha-Tocopherol and selenium concentrations in organs were very low. Dams of calves with WMD showed low serum tocopherol levels, 22% of which indicating deficient levels below 150 micrograms/100 ml. Serum selenium levels in dams showed a marked decrease to under 20 ppb, and also low blood GSH-Px activity. Feedstuffs supplied in the farms to affected calves indicated very low alpha-tocopherol contents (below 3 mg/100g DM) and low selenium concentrations below 50 ppb in DM. It was concluded that WMD in calves was attributable to nutritional muscular dystrophy caused by deficiencies in tocopherol and selenium in feedstuffs supplied to their dams. PMID- 2585930 TI - Diagnosis of Fasciola sp. infections in cattle by enzyme-linked immunosorbent assay. AB - An enzyme-linked immunosorbent assay (ELISA) was evaluated for diagnosis of experimental or naturally occurring Fasciola sp. infections in cattle. The positive rate for the ELISA in calves inoculated with Fasciola metacercariae were 21.1% by 2 weeks postinoculation (PI), 94.6% by 4 weeks PI and 100% by 6-21 weeks PI. The positive rate for the immunodiffusion test (Ouchterlony test) reached 91.7% by 2 weeks PI, however, it dropped to 77.8% by 10 weeks PI. The positive rate for the fecal egg examination was 0% by 10 weeks PI, 77.8% by 12 weeks PI and 100% by 14-21 weeks PI. The practical application of ELISA was tested by using 165 cows raised under field condition. All the 24 cows that were positive both in the fecal egg examination and the Ouchterlony test were ELISA positive. Of the 6 cows that were egg positive and Ouchterlony negative, 5 showed ELISA positive reactions. Of the 27 cows that were egg negative and Ouchterlony positive, 24 were ELISA positive. Of the 108 cows that were egg negative and Ouchterlony negative, 90 were ELISA negative. However, the other 18 cows had ELISA positive reactions. Our results suggested that the ELISA using crude adult antigen was superior to the Ouchterlony test and fecal egg examination for diagnosis of experimental or naturally occurring Fasciola sp. infections in cattle. PMID- 2585931 TI - Scanning electron microscopic studies on the red pulp of the mink spleen. AB - In order to obtain three-dimensional information on the fine architecture of the red pulp of the mink spleen, especially the circulation pattern in the red pulp, perfusion-fixed and freeze-cracked specimens were examined with a scanning electron microscope. A latticework was formed by elongated endothelial cells (rod cells) with side processes and the spongy reticular tissue. The outer surface of the sinus was covered with fine processes of reticular cells. Numerous sheathed arteries were found in the splenic cord. The sheath was composed of a few layers of flat reticular cells. The arterial capillaries of the red pulp opened directly into the cordal space. No evidence could be detected to prove or suggest any direct continuity between arterial capillaries and splenic sinuses. These results strongly support the concept of "open circulation", at least in the red pulp of the mink spleen, with the possibility of a "functionally closed circulation" under some physiological conditions. PMID- 2585932 TI - Effective administration of erythropoietin for renal anemia. AB - The erythropoietic effects of erythropoietin (EPO) have been investigated in the different administration schedule and injection routes. EPO was intravenously, intramuscularly or subcutaneously injected to partially nephrectomized anemic rats in 3 types of prescriptions (300 units of EPO per kg of body weight was respectively given in a dose at the first day, in 4 divided doses every 4 days, and in 7 divided doses every 2 days for 2 weeks). Repeated injections of EPO in divided doses caused stronger erythropoiesis than single injection. Especially, seven repeated injections promoted the strongest erythropoiesis. The serum iron concentration and reticulocyte counts suggested that erythropoiesis was continued less than 2 weeks after single injection but erythropoiesis in repeated injection groups had been accelerated for 2 weeks. Intravenous injections were less effective than either intramuscular or subcutaneous injections at 2 weeks after 7 repeated injections of 300 units of EPO per kg of body weight in 7 divided doses. Erythropoietic effects of EPO on the same total dose are dependent on the frequency of EPO injection and the durability of serum EPO concentration. On EPO usage, one bolus intravenous injection of excessive dose is considered to be wasteful and the repeating injections to maintain plasma EPO concentration is expected for the rational treatment of uremic anemia. PMID- 2585933 TI - Effects of carbamate, BPMC, on the central cholinergic functions and behavior of mice. AB - O-sec-butylphenyl methylcarbamate (BPMC), an anticholinesterase carbamate, was injected once (100 mg/kg, s.c.) or repeatedly (50 mg/kg/day for 10 days) into mice. Animals were examined for their behavior and for parameters of cholinergic activity in the forebrain. Mice that received only a single injection exhibited reduced ambulation, hypothermia, and impairment of rotarod performance for up to 3 hr after a single injection. BPMC increased levels of acetylcholine (ACh) in the forebrain for up to 6 hr, and decreased acetylcholinesterase (AChE) activity for up to 24 hr. Both high-affinity choline uptake (HACU) and binding of [3H]quinuclidinyl benzilate (QNB) were reduced 20 min after a single injection without any effect on choline acetyltransferase (ChAT) activity. In behavioral tests conducted 10 min prior to the daily injections, rotarod performance and ambulation were slightly impaired for a few days before and after cessation of injection. Repeated treatment decreased HACU and binding of [3H]QNB for 24 hr after the final injection without any changes in levels of ACh content, AChE activity and ChAT activity. BPMC may reversibly impair cholinergic functions through effects not only on AChE activity but also on HACU and binding of [3H]QNB. PMID- 2585934 TI - An experimental trial on embryo transfer in the dog. PMID- 2585935 TI - Occurrence of Yersinia spp. in migratory birds, ducks, seagulls, and swallows in Japan. PMID- 2585936 TI - Effects of PGF2 alpha-analogue administration during the luteal phase on the next estrous cycle in the bitch. PMID- 2585938 TI - Variability of prepatent period in Japanese Eimeria tenella strains. PMID- 2585937 TI - Detection of schizonts in chickens recovered from natural infection with Leucocytozoon caulleryi. PMID- 2585939 TI - Age-related changes in articular cartilage thickness of the third metacarpal bone in the thoroughbred. PMID- 2585940 TI - Susceptibility of Japanese Lymnaea ollula to Nigerian Fasciola gigantica. PMID- 2585941 TI - Establishment and characterization of a cell line (KU-8) from squamous cell carcinoma of the penis. AB - The KU-8 cell line was established from a lymph node metastasis of human squamous cell carcinoma (SCC) of the penis. The cells grew rapidly (doubling time 20 hours) as adherent monolayers, and were tumorigenic in nude mice. The carcinoma cells showed epithelial characteristics by observation with a phase contrast microscope. The cells retained the ultrastructural characteristics of squamous epithelium including tonofilaments and desmosomes. In addition to the morphological characteristics of SCC, this cell line preserved specific molecular markers of epithelium, such as desmoplakin, cytokeratin, and involucrin, all of which were demonstrated by immunofluorescent studies. Furthermore, SCC-related antigen (SCC-RA), a tumor marker for SCC, was produced in KU-8. Moreover, immunofluorescent study showed that KU-8 cell line expressed the specific receptor of epidermal growth factor (EGF), which turned out to increase the cell growth of KU-8. These results indicate that this new cell line could provide an excellent model for the basic research and development of new therapeutic modalities of penile carcinoma. PMID- 2585942 TI - A stress analysis of the proximal tibia after insertion of the endoprosthesis. AB - Detailed investigation for the local stress increment at the fixation post bottom of an artificial knee joint was performed by two-dimensional finite element method. A strain measurement was also conducted by wire strain gauges on a cancellous bone with a special method. It was made clear that a curvature with a certain extent of radius was necessary for the corner of a fixation post and application of acrylic cement with a certain extent of thickness (3 mm less than or equal to) was effective for stress relaxation, and that an optimum value (10( 1)-10 GPa) existed for elastic modulus of bone cement. PMID- 2585943 TI - Increase in red blood cell aggregability following experimental occlusion of the middle cerebral artery in cats. AB - Red blood cell (RBC) aggregability has been reported to be enhanced in patients with ischemic cerebrovascular disorders. We investigated whether the ischemic insult per se causes such enhancement of RBC aggregability. Fifteen cats were anesthetized and the middle cerebral artery (MCA) was occluded. Successful occlusion was confirmed from a sudden decrease in cerebral blood volume. Venous blood samples (2 ml) were obtained from the femoral vein before and after MCA occlusion. The blood was immediately mixed with disodium EDTA (2 mg), and the RBC aggregation rate (RBC-A) was measured employing a whole-blood RBC aggregometer. The control value for RBC-A was 0.213 +/- 0.007/s (mean +/- SEM). RBC-A was already increased at 1 h after the occlusion (0.229 +/- 0.007/s, p less than 0.01) and maintained a significantly high level until 2 h after the occlusion (0.229 +/- 0.018/s, p less than 0.05) as compared with the control value. These results suggest that a brief insult of cerebral ischemia brought about an enhancement of the RBC aggregability in the circulating blood. PMID- 2585944 TI - Serum amphotericin B concentration in a very premature infant with disseminated candidiasis. AB - A 1,040-g premature baby was diagnosed to have disseminated candidiasis and treated with amphotericin B (AMB) and 5-fluorocytosine. During the treatment, an unexpectedly large dose of AMB was infused unintentionally. AMB level was as high as 1.73 micrograms/mL soon after 5 mg/kg infusion instead of 0.5 mg/kg. However, it dropped rapidly to 0.83 micrograms/mL after 24 hours. AMB was detected in patient's serum at a higher level than minimal inhibitory concentration as long as one month after treatment was stopped. The patient showed liver dysfunction but no nephrotoxicity. The further studies are needed to establish safe and effective treatment regimen in premature infants with disseminated candidiasis. PMID- 2585945 TI - A 35-year-old woman with renal failure and pulmonary hemorrhage. PMID- 2585946 TI - [Evaluation of clinical efficacy of rifampicin in the treatment of nontuberculous mycobacteriosis from in vitro susceptibility testing]. AB - In vitro susceptibility testing of various mycobacteria (a total of 295 strains) to rifampicin was carried out using Ogawa egg medium and inoculation of 0.02 ml samples from 10 mg wet weight per ml suspensions, which were prepared from 10 day old cultures (M. tuberculosis, 21 day-old cultures; M. fortuitum, 3 day-old cultures). The minimal inhibitory concentration (MIC) was determined after incubation at 37 degrees C for 14 days (M. tuberculosis and M. xenopi 21 days and M. fortuitum 5 days). MIC of M. tuberculosis strains, which were isolated from patients who were untreated previously by any antituberculosis drugs, was in the range of 3.13 to 12.5 micrograms/ml, thus the critical concentration of rifampicin, in which the clinical efficacy of rifampicin could be expected, was determined as 12.5 micrograms/ml. The percentage of strains of each species which are susceptible to this critical concentration is shown in Table 1. In M. avium complex strains, 50% of the strains were inhibited by rifampicin equal to or lower than the critical concentration. However, it is considered to be difficult to cure the disease completely even in these cases, because of the lack of other effective combination drugs with rifampicin. Monotherapy with rifampicin or that with less effective combined drugs would result in development of rifampicin resistant population and failure of treatment. In successive studies, we will try to find out best possible combination drugs. From this study, the highest efficacy of rifampicin treatment was expected in the disease due to M. kanasaii and the lowest efficacy in the disease caused by M. fortuitum. PMID- 2585947 TI - [Tuberculosis and cancer: primary lung cancer cases after treatment with anti tuberculous drugs]. AB - Out of 939 primary lung cancer cases (histologically confirmed), 54 cases had received treatment with anti-tuberculous drugs before diagnosis of lung cancer was made. Fifty-one percent of the cases were detected by the mass survey and 55.6% of them were adenocarcinoma. The duration of treatment for tuberculosis was less than 3 months in 63.0% and more than 13 months in 5.6% of the cases. Surgery for lung cancer was performed in 25 cases (46.3%). The ratio of surgical intervention for patients previously treated with anti-tuberculous drugs was not different from that for patients who had received no anti-tuberculous drugs. PMID- 2585948 TI - [Effect of aging on the mode of Mycobacterium intracellulare infection]. AB - Effect of aging on the mode of Mycobacterium intracellulare infection was examined using female ddy strain mice of 6, 12, 24, 48, 64 and 80 weeks old. When mice were infected intravenously with M. intracellulare 31F093 (8 x 10(7] and the incidence and the degree of gross lesions in the lungs and viable number of the organisms in the lungs and spleen were studied at 8 weeks after bacterial challenge, there was no marked difference in the grade of pathological lesions by age. However, all the mice younger than 25-weeks of age survived over the period of 8 weeks after infection, whereas about 30% of mice older than 48-weeks of age died during the course of infection. Thus, it is thought that some parts of old mice were more susceptible to M. intracellulare infection than young mice on the basis of their survival. PMID- 2585949 TI - [M. kansasii lung infection occurring in a compromised host with idiopathic pulmonary fibrosis]. AB - A 61-year-old man was admitted to our hospital because of persisting cough, sputum and shortness of breath for four months. Brushing specimens and BALF bronchoscopically obtained revealed acid-fast bacilli and TBLB showed pathological findings consistent with interstitial pneumonia. Based on these results, clinical symptoms, chest roentgenograms on admission and identification of M. kansasii, a diagnosis of M. kansasii lung infection occurred in idiopathic pulmonary fibrosis was made. The patient's symptoms consistent with M. kansasii lung infection and his sputum became negative 6 weeks after antituberculosis chemotherapy with INH, SM and RFP. Because of an increasing dyspnea due to pulmonary fibrosis, however, the patient received oxygen therapy. This case suggested an increasing tendency of compromised hosts associated with M. kansasii lung infection. PMID- 2585950 TI - Stepfamily integration through development phases of adjustment. PMID- 2585951 TI - Down and out in their own hometown: assessing health of soupkitchen users. PMID- 2585952 TI - Predicting patient falls in an acute care nursing setting. PMID- 2585953 TI - Diary of a nursing research project. PMID- 2585954 TI - [Development of "endless loop tachycardia" after exhaustion of the power source of a DDD type pacemaker]. PMID- 2585955 TI - [Age-related characteristics of hemodynamics of the lesser circulation in bronchopulmonary diseases in Valsalva's test]. PMID- 2585956 TI - [Computerized tomography in evaluating the function of aortocoronary shunts]. AB - An examination was made of 38 patients undergone aortocoronary bypass surgery. Comparing the density of content in the aorta and shunt before and after bolus contrast in computerized tomography makes it possible to evaluate the patency of the aortocoronary shunt. A shunt patency coefficient (SPC) was proposed, which fitted the ratio of density differences in the shunt to those in the lumen of the ascending aorta before and after the injection of a contrast agent. SPC equal to 0.5 or more is indicative of a good patency of the aortocoronary shunt, but that being 0.3 or less suggests no or extremely poor function of the shunt. SPCs that are equal to 0.3-0.5 are transient indicators of its patency. PMID- 2585957 TI - [Diagnosis of critical stenosis of the coronary arteries in patients with ischemic heart disease]. AB - Possible diagnosis of critical coronary stenosis using a bicycle ergometry along with coronary angiography was studied in 193 patients. Informative hemodynamic criteria were proposed for noninvasive diagnosis of anatomic critical coronary stenosis during exercise. Application of coronary angiography combined with a bicycle ergometric testing enabled the true critical coronary stenosis to be diagnosed. PMID- 2585958 TI - [Duplex scanning in the diagnosis of diseases of the thoracic aorta]. AB - In the Department of Vascular Surgery, A. V. Vishnevsky Institute of Surgery, USSR Academy of Medical Sciences, Duplex scanning was used to examine 40 patients. It was demonstrated that 20 patients had aneurysms of the arch and descending thoracic aorta; 4, dissecting aneurysms of Types I and III; 5, aortic coarctation; 11 patients had thoracic aorta aneurysms resected. The optimal point for scanning in the diagnosis of aneurysms and coarctation of the thoracic aorta is the jugular fossa. The diagnostic value of the duplex scanning in the detection of aneurysms of the arch and descending thoracic aorta amounted to 90%, that of aortic coarctation, 100%. The technique is noninvasive and highly informative, assessing the results of surgical therapy of thoracic aorta abnormalities in late periods following operation. PMID- 2585959 TI - [Stability of the somatic and autonomic nervous systems during occupational activities]. AB - The paper deals with some experience gained in the use of systemic quantitation of behavior for diagnosing the functional status of a working man. Comparing the indices of the somatic and autonomic nervous system with the stage and end resultant parameters of practical activities made it possible to diagnose psychoemotional stress, to reveal a risk group and to develop a package of individual correction measures to promote the health of a working man. PMID- 2585960 TI - [Prevalence of risk factors and indicators of mortality among males 40-59 years of age with various forms of ischemic heart disease (data of a 5-year prospective study)]. AB - A collaborative study was undertaken to assess the efficacy of multifactor prevention of myocardial infarction and cerebral stroke. A representative group of 5951 males aged 40-50 years was examined in Kaunas. Coronary heart disease (CHD) was detected in 11.1%, including 2.7% who had a history of myocardial infarction, 2.5% had exertional angina, its painless type was found in 5.9%. In males with CHD, arterial hypertension, hypercholesterolemia, obesity were more common and smoking was more infrequent than in those without the disease. The results of the 5-year follow-up showed that CHD males had higher total and cardiovascular mortality and myocardial infarction morbidity rates than males without CHD. Males with prior MI and pain-free CHD significantly differed from those from the control group in total and cardiovascular mortality rates. No statistically significant difference was found in MI mortality and morbidity rates between male patients with exertional angina and controls. PMID- 2585961 TI - [Progression of coronary arteriosclerosis: its diagnosis and the possibilities of prognosis and control]. PMID- 2585963 TI - [Ultrastructure of myocardial capillaries in chronic ischemic heart disease]. AB - Intraoperative myocardial biopsy specimens taken from 50 patients with coronary heart disease were studied to examine ultrastructure of myocardial capillaries. It was found that this disease was characterized by abundant myocardial capillaries with a narrowed lumen. Quantitative stereological analysis indicated that the ultrastructure of the capillaries with narrowed lumen was not substantially different from that of open capillaries. The findings showed that the narrowed capillaries to be reserve and capable of providing an adequate blood supply of cardiomyocytes after aortocoronary bypass surgery. PMID- 2585962 TI - [Myocardial asynergy of the left ventricle in patients with aortic stenosis]. AB - Left ventriculograms obtained from 21 patients without any intracardiac hemodynamic abnormalities were analyzed by using the correlation method. The analysis revealed three functional areas of the left ventricle and defined normal values of their systolic and diastolic pulses. Hypo- and hyperkinesia of the functional areas in the left ventricle were quantitatively determined. Left ventricular cinematics was studied in 105 patients with aortic stenosis. Most patients of them were demonstrated regional cinematic abnormalities of various genesis. Local or total hypokinesia was detected in 62 per cent; hyperkinesia of its upper areas was found in a third; 7 per cent had normal dynamics of contraction in all the functional areas. It should be taken into account heterogeneous responses of the left ventricle to systolic overload while performing all investigations and studies or making clinical and prognostic assessments. PMID- 2585964 TI - [Effect of fructose-1,6-diphosphate on the size of the necrotic area and course of the acute period of experimental myocardial infarction in rats]. AB - The experiments on rats indicated that fructose-1,6-diphosphate substantially decreased the sizes of a necrotic zone, elevated myocardial ATP levels, reduced the edematization of lung tissue, shortened the duration of early postocclusive arrhythmias, and increased the latent period for their development. A dose dependent cardioprotective effect was found in the preparation. PMID- 2585965 TI - [Prevention of arrhythmogenic and contractile effects of excessive Ca2+ on the heart through adaptation to stress by increasing the activity of sarcoplasmic reticulum]. AB - The experiments with rat isolated hearts and papillary muscles showed that adaptation to short-term stresses increased myocardial resistance to arrhythmogenic and contractile effects of excessive Ca2+. Adaptation caused a three- and fivefold reduction in the contracture and premature beats, respectively, while Ca2+ levels were increased from 1.36 to 10 mM. In the experiments with papillary muscles, the adaptation showed a 6.5-fold decrease in the contracture and significantly limited resting potential depression resulted from lower Na+ concentrations (up to 9 mM) in the perfusion solution. The adaptation to stresses was found to restrict depression of cardiomyocyte electrophysiological parameters that was due to high Ca2+ levels and high heart rate. With the factors, the resting potential in adaptation proved to be significantly higher than in controls and the time of action potential was twice as such as in controls. Biochemical studies demonstrated that Ca2+ transport rates in the sarcoplasmic reticulum, cardiomyocytes of adapted animals were increased by more than 30% whereas the sarcoplasmic reticulum of the heart was more resistant to the effects of endogenous factors of degradation. The authors also discuss a possible mechanism of the cardioprotective effects of adaptation to stress undamaging exposures, which is associated with limited depression of electrophysiological parameters on pathological exposures and with increased Ca2+ transporting capacity of the sarcoplasmic reticulum. PMID- 2585966 TI - [Functional state of mitochondria, myofibrils and creatine kinase associated with these organelles of the myocardium in hamsters with hereditary cardiomyopathy]. AB - Functional states of the cardiac contractile apparatus and mitochondria were studied in hamsters with hereditary cardiomyopathy using myocardial fibers with sarcolemma, which had been exposed to saponin. This provided an opportunity of examining the respiratory characteristics of a total mitochondrial population in the myocardium of the animals of two ages (75-100 and 175-200 days). A higher calcium sensitization of myofibrils was found in hamsters with cardiomyopathy. Examination of the rigor tension-MgATP relationship in the presence or absence of phosphocreatine revealed that the animals showed a slightly lower functional activity of myofibrillar creatine kinase. The findings indicate that the creatine kinase system of cardiomyocytes is involved in hereditary cardiomyopathy, mitochondria, in particular, exhibiting much more profound disturbances, in other respects, myofibrils and mitochondria retain their basic functional properties. PMID- 2585967 TI - [Effect of obsidan on lymph flow and lymphatic microvessels]. AB - Life-time microscopy showed possible direct effects of obsidan on lymph vessels and flow in the experiment. With local application of the drug there was a short term constriction, higher frequencies and lower amplitudes of lymphangionic pulsation; during its intramuscular injection, sustained dilator effects, two phase shifts in the frequency and limitation of pulse amplitude were seen. With the two routes of obsidan administration heterogenous, unpersistent changes in the linear velocity of lymph flow were observed. PMID- 2585968 TI - [Transport of monovalent cations and calcium in erythrocytes of rats with spontaneous hypertension: study with fractions enriched with young and old cells]. AB - The erythrocytes from two spontaneously hypertensive rat strains (SHR and MHS) differ from those of control strains such as WKY and MNS in showing lower values of the mean volume and higher Na,K-cotransport rates. After 4-hour incubation in the presence of orthovanadate 45Ca levels in the erythrocytes from SHR was twice as high as in those from WKY. Under the same conditions, hemoglobin crystallization occurred, this process in SHR erythrocytes took place more intensively. No difference was found in these parameters between MNS and MHS. The fractions enriched with young and old cells remained to display variations in the mean volume of cells, Na,K-cotransport rates, 45Ca levels and hemoglobin crystallization, which were recorded between SHR and WKY. The WKY-SHR hybrids of second generation indicated that only Na,K-cotransport rates of the parameters examined positively correlated with blood pressures. From the findings it was concluded that the differences in the volume of erythrocytes and their permeability for cations were not due to the changed time course of cell aging in the blood bed, but to the specific characteristics of cytoskeleton protein arrangement, which were primarily typical of a rat reticulocytic membrane. PMID- 2585969 TI - [Aortocoronary shunting in the early period after myocardial infarction]. AB - Fourteen patients aged 34-54 years underwent aortocoronary bypass surgery for early postinfarction angina within 30 days following myocardial infarction. In periods up to 1.5 years after surgery, angina pectoris was not detected in the patients; cases of recurrent myocardial infarction were not registered. PMID- 2585970 TI - [Evaluation of risk factors in surgery of aneurysm of the abdominal aorta]. PMID- 2585971 TI - [Survival and mortality of patients with ischemic heart disease and concomitant arterial hypertension after conservative and surgical treatment]. PMID- 2585972 TI - [Clinico-pathophysiologic aspects of changes in lipid peroxidation and blood rheology in patients with hypertension after the general hypoxemic test]. PMID- 2585973 TI - [Surgical results in secondary nonspecific pleural empyema]. AB - During a 12-year period (1975-1987) 448 patients with secondary nonspecific pleural empyema have been treated--84.8 per cent males and 15.2 per cent females. In 78.1 per cent of the patients the empyema was complication of pneumonia and acute suppurative-destructive diseases of the lungs, in 9.6 per cent--of blunt chest trauma and in 6.3 per cent occurred after abdominal operations. Subtotal and total empyema had 46.7 per cent of the patients with acute empyema and 35.6 per cent of those with chronic empyema. It is pointed out that largely for subjective reasons the diagnosis and early adequate treatment of empyema was delayed which led to subsequent chronification. In 257 patients with acute empyema covered aspiration drainage was applied (89.9 per cent of the patients): 81.4 per cent were cured, 13.8 per cent experienced improvement and 4.8 per cent died. The most common surgical intervention in the 191 patients with chronic empyema was pleurectomy with decortication of the lung (57.6 per cent of the cases); 97.3 per cent of the operated patients were cured, 1.8 per cent improved and 0.9 per cent died. PMID- 2585974 TI - [The current concept of tumor markers in oncological urology--cell surface markers]. AB - Basic problem of the diagnosis and treatment of superficial noninvasive bladder cancer is the absence of criteria for its potential invasiveness. In recent years it became clear that cell differentiation in some cancer forms essentially depends on the presence or absence of some antigens on the cell surface. These may be demonstrated by means of appropriate methods and may thus serve as marker in determining the prognosis and the stage of the disease and for monitoring the therapy in patients with bladder carcinoma. Of major value for the clinical practice are the clinical practice are the T-antigen, the ABO(H) antigens and the tumor-assisted antigens. Demonstration of T-antigen is effectuated by means of a modified erythrocyte-binding test and of the ABO(H) antigens by the Davidsohn's test. Correlation of these antigens with the pathological and clinical stage in a series of studies has demonstrated their practical significance in choosing an optimal therapeutic plan. There also exists relationship between the blood group antigens and the degree of malignancy in urothelial tumors. This allows a more precise evaluation of the indications for organ-preserving operation in some cases. PMID- 2585975 TI - [Typical and atypical resections of the liver with 2 clinical cases]. AB - The development of resection liver surgery is discussed in a historical aspect. The basic topographic-anatomical guidelines, indications and different techniques of performance of atypical and typical liver resection are given. Two clinical cases of spacious liver resections are reported: resection of large hydatid cyst of the left lobe in a 16 years old girl and two liver resection for liver cystadenocarcinoma in a 25 years old woman. The advantages of applying top technical achievements in liver resection surgery are pointed out. PMID- 2585976 TI - [Infections and kidney failure in 100 surgical urology patients]. PMID- 2585977 TI - [Immunotherapy with Solco Urovac vaccine in chronic genitourinary infection]. AB - Twenty five patients with chronic urogenital infections (cystitis, pyelitis and prostatitis) were treated with Solco urovak infection which is active against Escherichia coli, Proteus, Klebsiella and Streptococcus fecalis organisms. This microbial flora has been isolated from these patients and proved resistant to the conventional antibacterial agents. The vaccine was very well tolerated, gave no side reactions, but transient short lasting rise of the temperature to 38 degrees C. The bacteriologic control on the 6. week after vaccination showed sterile urine in 68 per cent of the patients, no change in 20 per cent and recovery of other bacterial flora in 12 per cent. The vaccine is recommended for treatment of urinary tract infections caused by the microorganisms enumerated above. PMID- 2585978 TI - [A new method for treating Peyronie's disease]. AB - Results are reported of the treatment of Peyronie's disease by a laser-magnetic method. The "Ulamag" apparatus used is Soviet produce, based on helium-neon laser. For the period 1981-1988 a total of 713 patients have been treated. The method of treatment is described. The results were excellent in 114 patients (16 per cent), good in 535 (75 per cent) and satisfactory in 64 (9 per cent). Best results--complete cure--were obtained in patients in initial stage of the disease. In all others there occurred significant decrease in fibrous plaques size, softening and elasticity and disappearance of pain. All this helped to resume normal sexual life. PMID- 2585979 TI - [Volumetric indices of the left ventricle in patients with ischemic heart disease]. AB - In addition to the conventional indices of radionuclide angiography with ECG-gait in equilibrium, the authors determined the volume indices of the left ventricle at rest by the so-called nongeometric method in 30 patients with ischemic heart disease. Patients without myocardial infarct (13 subjects) had decreased total left-ventricular ejection fraction (EF), as a result of increase in the end systolic volume index (ESVI) in one of the tested patients. Changes in the regional fractions and in the wall kinetics were detected in 6, resp. in 8 patients. Patients with myocardial infarct--13 subjects--had decreased total left ventricular EF, as a result increased ESVI in 4 patients. Disturbances in the regional fraction and in the wall kinetics had 9 patients. Estimated for the whole group, the mean ESVI level was significantly higher than in the former group of patients. Patients with postinfarction aneurysm, in addition to the marked decrease of the total left ventricular EF, had increased and-systolic and diastolic volume index, which in some of the patients was associated with reduced stroke volume index. The minute flow levels were significantly lower than in the former two groups. Determination of the volume indices is an important supplement to the efforts to gain precise information on the functional state of the left ventricle and for evaluation of the hemodynamics and of the effect of complications which occur with the advancing of the ischemic heart disease. PMID- 2585980 TI - [Prevention of aspiration syndrome in general anesthesia]. AB - In 210 patients divided in 7 groups depending on surgical disease or pregnancy the authors estimated pH of the gastric content during the preoperative period. It was found that pH was below 2.5, i.e. the acid level of the gastric content was high enough to present a hazard for appearance of Mendelson's syndrome, should eventual regurgitation or aspiration occur during or after general anesthesia. In an effort to prevent aspiration syndrome, apart from the most reliable and well know precaution "empty stomach", the authors suggest premedication with antacid drugs before the operation. They have applied Almagel A or Cimetidin 30 min before the operative intervention. The acid level of the gastric juice was thus reduced for about 1 1/2 hours to pH levels higher than the critical 3.5, so that in the event of eventual regurgitation and aspiration the gastric content would not cause severe respiratory injury. With their suggestion for use of antacid drugs during the preoperative period the authors expand the preoperative preparation of the patient for general anesthesia with set purpose to prevent respiration (Mendelson's) syndrome. PMID- 2585981 TI - [Unresolved and debatable questions on the problem of appendicitis]. AB - On the basis of histomorphologic examination of: 9907 biopsy specimens from appendix, obtained after its surgical removal because of appendicitis, 228 cases of senile involution of the appendix and appendix specimens from 125 children 30 days to 8 years of age who had been immunized with BCG vaccine intracutaneously and have died of miscellaneous diseases, the author debates on some poorly specified and moot points in the appendicitis problem. Appendicitis is sometimes considered a phase and in other cases a form of the disease. It is assumed that chronic appendicitis, as well as primary chronic appendicitis not preceded by acute inflammatory changes in the appendix, do exist. Sufficient morphologic criteria to distinguish chronic appendicitis from senile involution of the appendix are believed to exist. PMID- 2585982 TI - [Problems in early diagnosis of stomach cancer]. PMID- 2585983 TI - [Surgical treatment of stress ulcer]. AB - Results are reported of the operative treatment of stress ulcers by a refined method of selective proximal vagotomy (SPV), selective vagotomy (SV) with distal resection (DR) completely preserving the blood supply to the stomach along the minor curvature. For the period 1981-1988 a total of 82 patients with severe hemorrhage from stress ulcers have been treated. Thirty two of them were operated. In 2 patients SPV was performed by a modification suggested by the author and in another 6--SV also by modified technique with antrectomy B I. All patients recovered, none of them died. The results were compared with those in classical resection (17 operations, 1 reoperation, 12 repeated hemorrhagic episodes, 14 lethal cases) and with ulcer suturing (7 operations, 2 reoperations, 2 repeated hemorrhagic episodes, 7 lethal cases). The methods of SPV and SV with DR are recommended by the author as methods of choice, as they are pathogenetically grounded: satisfactory anacidity is achieved and the perfusion capacity of the stomach is preserved. PMID- 2585984 TI - [Short-acting anesthesia in cosmetic surgery of the breasts]. AB - Fourteen patients subjected to short-term cosmetic operations on the mammary glands comprise the study group. Anesthesia was performed with ketamine 0.07 mg/kg/min, applied against the background of droperidol 0.1 mg/kg or diazepam 0.2 mg/kg and spontaneous ventilation with nitrous oxide and oxygen in proportion 3:1. At the end of the ketamine anesthesia 1.0 g pyracetam was applied. There was negligible decrease in the systolic arterial pressure and decreased occurrence of psychotic reactions during the early postoperative period. PMID- 2585986 TI - [A case of a chronically complicated form of terminal ileitis]. PMID- 2585987 TI - [Functionally inactive carcinoma of the adrenal gland]. PMID- 2585985 TI - [A case of acute surgical abdomen and Curtis' syndrome]. PMID- 2585989 TI - [A case of an S-shaped kidney complicated by calculosis and hydronephrosis]. PMID- 2585988 TI - [Acute intestinal invagination in an infant facilitated by mesenterium commune]. PMID- 2585990 TI - [A case of a combined anomaly of the excretory system]. PMID- 2585991 TI - [A case of iatrogenic rupture of the urethra with a retrovesical urinoma]. PMID- 2585993 TI - [The mask lift--an improved concept for correcting the aging face]. AB - The operative interventions for correction of the ageing face have passed through an almost centenary development. Starting from simple skin excision, then through broad skin separation, reshaping of the platysma and cutting bands from the superfascial musculo-aponeurotic layer, one reaches to the present method of subperiosteal facial correction. Mask lift allows to obtain a more radical esthetic effect, creating facilities for remodelling of individual elements of the facial skeleton as well. The technique was applied on three patients with a very good esthetic result. PMID- 2585992 TI - [A case of metastasis of a kidney carcinoma to the epididymis]. PMID- 2585994 TI - [The use of a transabdominal method in treating inguinofemoral hernia simultaneously with surgery of the rectum or sigmoid in carcinoma]. AB - Detailed description is given of inguinofemoral herniotomy with subsequent plastic repair through transabdominal approach simultaneously with radical oncologic operation of sigmoid and rectum. The plastic repair is a two-stage procedure: The first stage consists of suturing the musculo-aponeurotic part of m. transversalis and m. obliq. internus abdominis to lig. inguinalis or lig. inguinalis to lig. Cooperi in femoral hernias. The second stage is the "ampoxen" explant, which is sutured cranially to f. transversalis, medially to the fascia behind m. rectus abdominis, downward to the public or obturator fascia and laterally to the fascia over m. iliopsoas. The explant serves as a firm "umbrella" from the internal part of the entire inguinofemoral area. The method was applied on 7 patients with very good postoperative result. PMID- 2585995 TI - [Complications of endoscopic retrograde cholangiopancreatography]. PMID- 2585996 TI - [Cell density of the corneal endothelium following cataract surgery]. AB - Endothelial cell loss following extracapsular cataract extraction and implantation of a posterior chamber lens was studied and the influence of various factors analyzed. In 56 eyes, the mean reduction in cell density in the superior zone of the cornea was 19%. In the eyes with epithelial edema endothelial damage was more severe than average. Lower cell density was also found in particular in patients over 75 years old and those with pre-existing cornea guttata. In contrast, preexisting glaucoma, a history of corneal trauma, and, astonishingly, the surgeon's experience had no detectable influence on endothelial cell damage. PMID- 2585997 TI - [Partial external trabeculectomy]. AB - The authors show that with the Excimer laser partial trabeculectomy can be performed, a procedure in which the juxtacanalicular meshwork is removed while the other layers remain untouched. It was proved in experiments on ten enucleated human eyes that at most 3% of the outflow resistance is localized in the uveal and sclerocorneal meshwork. The clinical applicability of partial trabeculectomy was demonstrated on five eyes. PMID- 2585998 TI - [Bromocriptine: a new therapy concept in the treatment of chronic recurrent uveitis?]. AB - Chronic recurrent uveitis still responds unsatisfactorily to therapy. Prolactin, a pituitary hormone that attains high blood levels physiologically in stress situations, has an immune modulating effect. The prolactin antagonist bromocriptine (2 x 2.5 mg/day) was administered prophylactically to prevent recurrence in seven patients with chronic iritis/iridocyclitis or panuveitis (Group A). On this therapy two patients suffered a mild recurrence (in one case in the first month). Another patient developed rebound uveitis after discontinuing bromocriptine medication. Tolerance appears to vary considerably, and in three patients the therapy had to be discontinued because of arterial hypotension and congestive rhinopathy, respectively. The three patients in Group B (with iritis, sympathetic ophthalmia, and intermediate uveitis) received bromocriptine in addition to cyclosporin A after plasmapheresis. This combination resulted in an elevated cyclosporin A plasma level, and the dosage was reduced by 30-50% (plasma level 70-120 ng/ml). With this lower dosage of cyclosporin A, the creatinine level of one of the patients returned to normal. Viewed on the basis of these initial results bromocriptine would appear to reduce the number of recurrences of chronic uveitis. Moreover, the synergism with cyclosporin A, described both theoretically and in an animal model in the literature, appears attainable in therapy. PMID- 2585999 TI - [Detection of cystoid macular edema with orally administered fluorescein]. AB - To detect cystoid macular edema after extracapsular cataract extraction, the authors used indirect ophthalmoscopy after oral application of fluorescein, rather than intravenous fluorescein angiography. The patients drank 10-20 ml 10% fluorescein sodium in 250 ml orange juice. Ophthalmoscopy was performed 30-45 minutes later using an exciter filter. Twenty-five patients with a tentative clinical diagnosis of cystoid macular edema were examined in this way. In six of them a manifest edema was detected. The results were confirmed by intravenous fluorescein angiography. PMID- 2586000 TI - [Absorption and fluorescence spectrometry measurement of intraocular lenses]. AB - Light absorption and fluorescence measurements can be used to detect accumulations of small molecules in intraocular lenses (IOLs). It was shown that HEMA IOLs can store and to some extent release a variety of drugs and fluorescein. PMMA and silicone IOLs, however, do not have this characteristic. UV blocking IOLs absorb UV light completely. The absorption limit varies between 390 and 410 nm, depending on the make. Neither absorption nor fluorescence response were affected by exposure to UV light or heat. PMID- 2586001 TI - [Indentation of the cornea and tonometry. Registration of the T-forces]. AB - Using the probe of the Stepanik Arteriotonograph, the T-forces induced in corneal tissue by indentation and their correlation with various intraocular pressure levels were recorded for the first time. The study was performed on enucleated human eyes. The results indicate that when performing tonometry a corneal indentation of more than 0.6 mm should be avoided. PMID- 2586002 TI - [Endophthalmitis phakoanaphylactica with anterior uveitis of the partner eye]. AB - Phakoanaphylactic endophthalmitis is a rare but deleterious complication of surgical, traumatic, or spontaneous lens capsule perforation. The authors describe a 79-year-old patient who developed severe endophthalmitis four days after extracapsular cataract extraction and implantation of a posterior chamber lens. The inflammation, which led to phthisis and eventually necessitated enucleation, was characterized by an atypical hypopyon in the form of a conglomerate of fibrin and cellular elements originating at pupillary level. The laboratory workup revealed a chronic lympho-granulomatous inflammation with epitheloid cells and polynuclear giant cells near the lens capsule, confirming the clinical diagnosis of a phakoanaphylactic endophthalmitis. Ten weeks after the cataract extraction a persistent iridocyclitis developed in the fellow eye, which had been free of inflammation up to that point. Hypotonia of the globe, a previous opacification of the first eye, the close chronological relationship with the phakogenic inflammation of the first eye, and clues from the literature suggest a sympathizing phakoanaphylactic endophthalmitis in the fellow eye. Differential diagnosis to rule out other postoperative inflammatory reactions, e.g., bacterial endophthalmitis, toxic lens syndrome, pseudo-phakoanaphylactic endophthalmitis, and sympathetic ophthalmia is described. PMID- 2586004 TI - [Chorioretinitis in miliary tuberculosis]. AB - The author presents a case of tuberculous chorioretinitis in a patient with miliary tuberculosis. Miliary tuberculosis with ocular involvement has become rare, because with modern chemotherapy miliary spread can usually be prevented. The chorioretinal changes, which in this case were completely reversible, are described and illustrated with fundus photos and angiograms. PMID- 2586003 TI - [Rheologic findings in patients with Eales disease]. AB - In a retrospective analysis of findings in 12 patients with Eales' disease significant changes in blood fluidity were established. The six female and six male patients, aged between 15 and 59, were examined in the acute and subclinical stages and when a recurrence occurred. The rheologic parameters plasma viscosity, erythrocyte rigidity, and erythrocyte aggregation were significantly increased in the acute stage and when there was a recurrence, while in the subclinical stage the rheologic values improved to normal. No correlation could be found between the severity of the clinical picture in the various phases and the rheologic values. None of the other biochemical, microbiologic, and immunologic parameters were pathologic in any stage of the disease. In particular, virus serology, protein, immune, and hemoglobin electrophoresis were normal in all patients. While the etiology of Eales' disease remains unknown, deteroration in erythrocyte rigidity appears to play a part in the pathophysiology of the disease. PMID- 2586005 TI - [Recording and analysis of the electrooculography using a personal computer. Initial experiences with normal probands and patients with diseases of the posterior eye segment and intraocular foreign bodies]. AB - The electro-oculogram (EOG) is recorded by a personal computer and analyzed during the examination. If the results obtained with this method in normal subjects are compared with the conventional method (with which data recorded in analog form have to be measured manually), there is no significant difference. In patients with diseases of the posterior segment (e.g., posterior uveitis) or intraocular foreign bodies the results of computer and manual analysis are also practically identical. There are two computer analysis techniques: for subjects with almost normal EOGs the trigger-independent method is sufficiently accurate. In patients with pathologic EOGs, however, and in particular those with small potential differences, the trigger-related method is more likely to lead to correct results. The analysis path can be displayed on the computer monitor at any time, so that the examiner can always check whether it is correct. In contrast to manual analysis, the computer analysis cannot be influenced subjectively by the examiner. This considerably improves the comparability of examination results. A further advantage of computer analysis is its speed: the result is available immediately following the examination. It is a low-cost system which is easy to install and use, and thus suitable for routine clinical work. PMID- 2586006 TI - [Drug trials in clinical practice--aspects of drug safety]. PMID- 2586007 TI - Prevention of amphotericin-B-induced nephrotoxicity by loading with sodium chloride: a report of 1291 days of treatment with amphotericin B without renal failure. AB - An open, prospective study was performed to evaluate the clinical usefulness of sodium chloride loading for prevention of amphotericin-B-induced nephrotoxicity in 37 patients requiring 44 courses of amphotericin B treatment. The median duration of the treatment course was 22 days (range, 9-136 days), and mean cumulative dose per patient was 1117 mg (range, 231-7831 mg). During amphotericin B treatment, all patients received 50 to 100 ml of 10% sodium chloride (85 to 171 mmol NaCl) via an intravenous line for prevention of amphotericin-B-induced nephrotoxicity evaluated by serum creatinine levels. Using this regimen, none of the patients developed significant nephrotoxicity (increase in serum creatinine of more than twice baseline level, or serum creatinine level greater than or equal to 2.0 mg/dl, respectively) despite the co-administration of other potentially nephrotoxic drugs. It was not necessary to discontinue treatment with amphotericin B in any of the patients. There were no side effects due to sodium chloride loading. Our results demonstrate that sodium chloride loading is useful for the prevention of amphotericin-B-induced nephrotoxicity. PMID- 2586008 TI - Tumor-associated trypsin inhibitor in patients with chronic pancreatic diseases. AB - Serum TATI (tumor-associated trypsin inhibitor) was measured in 41 control subjects, 30 patients with pancreatic cancer, 53 with chronic pancreatitis, and 47 with extrapancreatic diseases, mainly of gastrointestinal origin. TATI was found to be elevated in some subjects in all groups of patients; patients with chronic pancreatitis studied during an acute exacerbation of the disease had the highest percentage (68%) of pathological values. TATI was found to be correlated with elastase 1, tissue polypeptide antigen, and total and pancreatic isoamylase. A significant relationship was also found between TATI and serum creatinine levels. PMID- 2586009 TI - Natural history of HIV-infection in hemophiliacs: clinical, immunological, and virological findings. AB - At our institution 686 hemophiliacs are being treated. Of them 402 (59%) are anti HIV-seropositive. The general use of heat-treated clotting factor products was begun in July 1983, and from May 1984 all patients exclusively used heat-treated clotting factors. Thus, one can assume that infection occurred no later than early 1984 in our patients. Since December 1985 HIV-positive hemophiliacs have regularly been clinically and immunologically examined. Most of the 306 patients who could be investigated were clinically symptom-free at the time of their first visit. However, 45 patients have developed AIDS from 1982 through August 1988. The mean survival time of hemophiliacs with AIDS is less than 6 months. In 36% of those 274 patients who have been followed for a mean period of 14 months the clinical stage of the disease worsened by at least one stage according to the classification system proposed by the Centers for Disease Control. We did not find a correlation between clotting-factor consumption during the years 1984-1986 and the actual clinical stage of the patients. Virus isolation from peripheral blood lymphocytes (PBIs) answered the question whether anti-HIV seropositive hemophiliacs are not only immunized but really infected in many more cases than those revealed by detection of p24 antigen or decline of p24 antibody. Positive viral culture correlated strongly with a drop in CD4+ lymphocytes under the level of 400/microliters. However, HIV could not be cultured regularly in advanced cases, suggesting that virus replication in PBLs is not necessarily the cause of depletion of T-helper cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2586010 TI - Qualitative and quantitative changes in platelets after coronary-artery bypass surgery may help identify thrombotic complications and infections. AB - We studied the effect of coronary-artery bypass surgery on blood cells and platelets. Hematological parameters of eighty-three patients were measured by an automated cell counting and sizing analyzer. Sampling time was from 24 h prior to 10 days after surgery. During this time leukocytes and platelets showed characteristic changes in numbers and size, whereas red blood cells revealed no typical modifications. Even though it seems clear that changes of hematological parameters occur after bypass surgery, it is important to be aware of the actual extent of such changes. Therefore the data of 50 patients who had had no post operative clinical complications were combined to generate diagrams of those parameters that had changed in a characteristic fashion. The diagrams showing average changes, and 99% confidence intervals in mean platelet volume and platelet count were able to identify seven (out of 7) cases with complications up to 48 h before clinical signs were apparent. Complications ranged from mild (3 cases with infections) to severe (4 cases with thrombosis, embolic thrombosis and/or reinfarction). Diagrams showing changes in leukocyte parameters were able to identify only two cases with infections. Even though the number of cases is yet small, the results suggest that surveillance of platelet parameters may be useful in postoperative care. Furthermore, this study was able to confirm the recent findings of Trowbridge and Martin that an abnormal increase in platelet volume distribution width and low platelet counts found in patients with coronary heart disease may serve as good indicators for the prethrombotic state and the risk of myocardial infarction. PMID- 2586011 TI - [Automated microfluorometric absolute count and maturation analysis of reticulocytes]. AB - The absolute reticulocyte count and the maturation distribution of blood reticulocytes can be obtained by automated microfluorometric analysis in a deposit system called AURAS (Automated Reticulocyte Analysis System). Moreover visual measurements are possible on the same specimen for cell individual control. Visual reticulocyte counts are of high reproducibility and accuracy and therefore deliver practicable reference data. Results from experimental work indicate the value of maturation distribution changes with respect to Erythropoietin effects. PMID- 2586013 TI - [Critical evaluation of fructosamine as a control parameter in the assessing diabetic metabolic control]. PMID- 2586012 TI - Rapid onset of uricosuria after oral administration of irtemazole, an uricosuric substance. AB - A single 50 mg dose of irtemazole was given orally to ten healthy male volunteers. The onset of effects was tested. Plasma uric acid began to decrease 15 to 25 min after irtemazole was administrated. Renal uric acid excretion and uric acid clearance increased 10 to 20 min after drug administration. Maximal renal uric acid excretion (mean 197.4 mg/h) and maximal uric acid clearance (mean 78.4 ml/min) were reached after 15 to 55 min. No side effects were observed. The effects of irtemazole occur earlier than those of benzbromarone. The therapeutic effects of long-term therapy remain to be investigated. PMID- 2586014 TI - Haemolytic crisis after acetaminophen in glucose-(6)-phosphate dehydrogenase deficiency. PMID- 2586016 TI - Cardiac function in endocrine diseases: I. Acromegaly. AB - The aim of our echocardiographic study was to characterize cardiac function and anatomy of 14 acromegalics (A: 9 women, 5 men; mean age: 42.4 yrs) more closely. The duration of acromegaly in 4 of these patients was between 3 and 12 years; the disease was diagnosed for the first time in the other patients. Double M-mode echocardiography was performed in all patients and the results compared with data obtained from a control group of 24 healthy volunteers (N: 22 men, 2 women; mean age: 23 yrs). The mean left ventricular diameter at end-diastole was greater in the acromegalics than in the controls (A: 55 +/- 6 mm, N: 50 +/- 4 mm; p less than 0.005, means +/- SD). After correction for age and body surface area, it, however, was outside the 95% confidence interval in 5 patients. Left ventricular hypertrophy was present in 3 patients, one of whom had coexistent arterial hypertension. A total of 3 patients were hypertensive. Significantly higher values for the maximal velocity of systolic wall thickening (A: 6.1 +/- 0.6 cm/s, N: 4.2 +/- 0.6 cm/s, p less than 0.001) and diameter change (A: 12.4 +/- 2.0 cm/s, N: 10.6 +/- 1.0 cm/s, p less than 0.005) indicate increased contractility with concurrently increased relaxation; fractional shortening did not differ significantly (A: 38 +/- 5%, N: 37 +/- 5%, ns). The isovolumetric relaxation period at diastole was slightly longer in the acromegalics (A: 70 +/- 17 ms, N: 61 +/- 13 ms, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2586017 TI - Quantification of the heart rate-independent vasodepressor component in carotid sinus syndrome. AB - In 45 patients with carotid sinus syndrome, the heart rate-independent vasodepressor component under ventricular and av-sequential pacing of the heart was investigated both in supine and in standing patients. Under both forms of pacing, the carotid pressure determination has led to a marked lowering of systolic and diastolic arterial blood pressure which is significantly more pronounced under orthostasis. The blood pressure values reached both in supine and in standing patients are significantly higher under av-sequential pacing than under ventricular pacing. Accordingly, the proportion of symptomatic patients is less under av-sequential pacing in the supine position (17% versus 29%) and in standing (65% versus 83%). The heart rate-independent vasodepressor reaction is maximal on average between 11 s and 16 s after the beginning of the carotid pressure test and persists for 3 s to 7 s. The blood pressure reaches initial values again after 14 s to 20 s. To summarize, these data document that a clinically relevant heart rate-independent vasodepressor reaction is to be reckoned with in the majority of patients with carotid sinus syndrome. This shows a different time course than the vagally determined effect of the carotid sinus reflex on heart rate. Orthostasis intensifies the vasodepressor reaction so that the hemodynamically more favorable av-sequential pacing which is actually more favorable in hemodynamic terms cannot guarantee freedom from symptoms in the majority of patients in the upright standing position. PMID- 2586015 TI - [Effect of bradykinin on systemic and pulmonary hemodynamics in the human]. AB - In our studies we investigated the vasodepressor effects of bradykinin in vivo in normotensive and hypertensive subjects. Bradykinin was injected intravenously and intraarterially (40-6050 pM/kg) respectively was infused intraarterially (40-6050 pM/kg/min). The investigations were performed in 21 normotensives and 15 hypertensives. Bradykinin injections were performed after the following pharmacological interventions: salt restriction (10 mmol Na/d), salt loading (300 mmol Na/d), captopril (50 mg), ramipril (5 mg), lisinopril (20 mg), ketotifen (2 x 1 mg), indomethacin (2 x 50 mg), and propranolol (80 mg). The results show that bradykinin lowers blood pressure dose related by marked reduction in peripheral vascular resistance. The blood pressure reduction was strongly correlated with the increase in kinin concentration. This effect of bradykinin appears to be independent of changes in sodium metabolism, of beta adrenoceptors, of histamine 1 receptors, and of prostaglandins. ACE-inhibitors potentiate the blood pressure lowering effect of bradykinin about 20- to 50-fold. In case of an intraarterial injection of bradykinin in only 2-5% o the intravenously used dose of bradykinin are needed to produce an identical fall in blood pressure. From this experiments a pulmonary clearance rate of bradykinin over 95% can be calculated. In the pulmonary arteries bradykinin has no effect on the vascular resistance. In patients suffering from primary or renovascular hypertension the blood pressure response to bradykinin was enhanced. The bradykinin potentiating effect of the ACE-inhibitors was not altered in the hypertensives. In patients suffering from bradykinin hypertension or primary hyperaldosteronism bradykinin developed the same blood pressure lowering effect as in the normotensives. PMID- 2586019 TI - [Management of increased cholesterol values in general practice--results of a survey of established primary care physicians]. AB - In connection with a large population screening (N = 24317) in Bielefeld/Federal Republic of Germany a physicians inquiry has been carried out with a return of 55 out of 105 general practitioners or internists (52.4%), about 60% practicing already more than 10 years in Bielefeld. Only 42% of the answering physicians determine cholesterol in every new patient. Only 13% used own laboratory equipment, only 4% dry chemistry (almost indispensable for screening purposes). About 35% consider cholesterol lowering drug therapy to be necessary only beyond values of 300 mg/dl total cholesterol, the mean borderline value for the prescription of cholesterol lowering drugs was 265 mg/dl. Especially positions of shorter practice experience seemed to be sceptical taughts pharmacological means. The most utilized pharmacological preparations in Bielefeld correspond well with the "Arzneiverordnungs-Report '88". Side effects seem to be frequent as only three positions indicated that none of the patients under drug therapy had reported unwanted effects. Most physicians considered dietary therapy to be less effective than drug therapy. Almost all of them took means to increase the compliance of their patients, mainly (82%) through at least three monthly consultations. The prevalence of patients under cholesterol lowering dietary or pharmacologic therapy varied from 5 to 65% with the median of 17.5% which indicates a considerable underdetection of cases. However, physicians seem to be conscious about that as almost 80% hold more public information on cholesterol for desirable or (60%) very desirable. PMID- 2586018 TI - Interference of different ACE-inhibitors with the diuretic action of furosemide and hydrochlorothiazide. AB - In healthy volunteers the acute effect of furosemide (40 mg i.v.) and hydrochlorothiazide (100 mg p.o.) on diuresis, natriuresis and renal kallikrein and kinin excretion was investigated. Furosemide stimulated markedly diuresis and natriuresis as well as urinary kallikrein and kinin excretion. Pretreatment by captopril (C) reduced the diuretic and natriuretic effect of furosemide significantly probably due to a diminished (about 50%) proximal-tubular secretion of furosemide. Captopril did not alter significantly the furosemide induced changes in urinary kallikrein and kinin excretion. After captopril there was a clear dissociation between aldosterone, which was diminished by captopril continuously, and renal kallikrein and kinins, which were still stimulated by furosemide. These results suggest that renal kallikrein-kinin system is stimulated by furosemide directly and independently of aldosterone secretion. Other ACE-inhibitors like ramipril (5 mg) or enalapril (20 mg) did not influence the stimulatory effects of furosemide on diuresis or kallikrein-kinin excretion. Ramipril at a dose of 10 mg, however, enhanced the initial diuretic effect of furosemide by increased furosemide secretion and increased relative sodium excretion. Hydrochlorothiazide induced a prolonged diuresis which was not changed by either captopril or ramipril. Urinary kallikrein excretion was not stimulated by hydrochlorothiazide. Our results show an important drug interference between captopril and furosemide, which is independent of ACE-inhibition and probably only due to an interference in proximal-tubular secretion of both drugs. Between captopril and hydrochlorothiazide no such interaction could be observed. PMID- 2586020 TI - Tellurium-intoxication. AB - Tellurium is one of the rarest elements on earth. Intoxications are rare and almost exclusively occupationally exposed workers are affected. Only a few cases of non-occupational poisoning have been reported so far. Severe poisoning results in respiratory depression and circulatory collapse. After occupational exposure main symptoms and signs include loss of appetite, dryness of the mouth, suppression of sweating, a metallic taste in the mouth, and most notable, a sharp garlic odor of the breath, sweat and urine. We report our findings in a 37 year old, non-occupationally exposed woman with tellurium intoxication. PMID- 2586022 TI - [Malignization of trophic leg ulcers]. AB - The paper treats of the diagnostic and therapeutic results for 40 cases of lower limb trophic ulcers transformed into malignant. The frequency of the malignant transformation and the ulcer site and area are found to correlate. The underlying cause of the ulcer onset and the time from its diagnosis to the first signs of the malignancy have been elucidated. Clinical features of the ulcer malignant transformation, methods of differential diagnosis and therapeutics are described. PMID- 2586023 TI - [A case of tussive syncope syndrome]. PMID- 2586024 TI - [A case of histiocytosis X]. PMID- 2586021 TI - [Type I oxalosis in childhood--studies within the scope of terminal renal failure in the child]. AB - The difficulties of biochemical diagnosis in children and in chronic renal failure are discussed in detail, as well as the development of diagnostic and therapeutic possibilities in recent years, exemplified by 4 cases. Excretion of oxalate (and glycolate) may be incorrectly assumed to be normal with: a) uncritical application of the method of measurement, b) disregard of the clearly lower oxalate excretion in children (values should be referred to m2 of body surface), c) disregard of a decreased glomerular filtration rate (values should be referred to the creatinine clearance). With compromised renal function the excretion of oxalate and glycolate in primary oxalosis drops to "normal" whereas plasma values increase considerably. In this case the biochemical diagnosis is possible only by measurement of plasma values of glycolate and oxalate. Consequently, extensive extrarenal deposition of calcium oxalate crystals will, as a rule, become clinically manifest only after chronic renal failure has turned irreversible. In recent years, several therapeutic procedures, have been developed. They are of therapeutic significance for the early stages of the disease as well. Observing especially conditions renal transplantation or combined hepatorenal transplantation can be managed with a successful outcome. As the perioxisomal enzyme is activated only in the liver cells, an early liver transplantation as a definitive treatment by enzyme replacement may be the successful therapy in the future. PMID- 2586026 TI - [Ulcer of the ascending colon with fistula into the duodenum]. PMID- 2586025 TI - [A case of hallucinogen-like action of glaucine]. PMID- 2586027 TI - [Free intra-abdominal body]. PMID- 2586028 TI - [A case of generalized sarcoidosis with predominant lesions of the organs of the abdominal cavity]. PMID- 2586029 TI - [A case of Moschkowitz disease]. PMID- 2586030 TI - [Spontaneous panniculitis (Rothmann-Makai syndrome) in athletes]. PMID- 2586031 TI - [Advantages, problems and prospects of intragastric pH-metry (concerning V. A. Gorshkov's article, "Imaginary and real advantages of gastric pH-metry")]. AB - Analysis of V. A. Gorshkov's controversial article has demonstrated that approaches to the use of intragastric pH-metry and aspiration titrimetry should be differentiated depending on the aims, tasks and conditions of the examination. The original techniques of intragastric pH-metry have been proposed for the more effective use of this method of examination. PMID- 2586032 TI - [Phases of peptic ulcer]. PMID- 2586033 TI - [At variance with classification of amyloidosis]. PMID- 2586034 TI - [Pneumonia of the single lung]. PMID- 2586035 TI - [Diagnosis, treatment and quality of life]. PMID- 2586036 TI - [Plasmapheresis in combined treatment of severe forms of abscesses and gangrene of the lungs]. AB - With an adjuvant course of plasmapheresis, a combined treatment of severe acute abscesses and gangrene of the lungs brought about a marked short-term clinical response in 48 out of 50 treated patients. The responders had their temperature returned to normal, amount of sputum significantly reduced. They recovered good appetite and gained weight. There was also attenuation of DIC syndrome and endotheliosis, improvement of cellular and humoral immunity. Upon the discharge 35 patients had complete or partial response, 10 patients developed a chronic process. Lethal outcomes reached 10%. PMID- 2586037 TI - [Intravascular laser irradiation of blood in the treatment of patients with lung abscess]. AB - Intravascular blood laser irradiation has been introduced into a multimodality treatment of pulmonary abscesses in 47 patients. Intracavitary laser irradiation of the abscess or pleural empyema was performed in 10 cases. A suggested detoxication and immunostimulation related to the laser therapy was confirmed. The highest efficacy of the treatment was found for chronic pulmonary abscesses, the least one in decompensation associated with multiorgan failure. PMID- 2586038 TI - [Levamisole and splenin in combined therapy of patients with bronchiectasis]. AB - Follow-up of 114 patients with bronchiectasis has demonstrated that immunomodulation agents levamisole and splenin included in combined treatment augment their therapeutic effect and normalize the immune status of patients. This is manifested by normalization of the amount and functional activity to T lymphocytes, the content of IgG, IgM and IgA and the autoimmune shifts. A favourable effect was encountered significantly more often than that in patient who were treated by the traditional methods without the use of the immunomodulation agents and in those who were given only levamisole and splenin together with anti-bacterial and hygienic therapy. PMID- 2586039 TI - [Determination of most important clinico-immunologic indicators in differential diagnosis of sarcoidosis and histiocytosis X of the lungs]. AB - The results of mathematical treatment of the clinical and immunological parameters are analysed in 17 patients with sarcoidosis and in 17 with pulmonary histiocytosis X. Function of separation and clinical and immunological parameters which are most essential for differential diagnosis have been determined by the separation plane method. This work allows one to improve differential diagnosis and establish correct diagnosis of these diseases without resorting to invasive methods of examination. PMID- 2586040 TI - [State of the ventilatory function of the lungs in heavy smokers]. AB - Computed spirography, He/O test and capnography evaluation of external respiration has been carried out for 52 subjects. Of these 27 were nonsmokers, 25 smoked but had no history of respiratory diseases. The integral criteria of external respiration obstruction (MOCmax, MOC50, MOC75) proved inadequate diagnostic tool for early detection of ventilatory alterations in smokers who are at risk to develop chronic nonspecific pulmonary diseases. Pharmacological tests, He/O investigation and capnography did reveal defects in small bronchi permeability in all the smokers. Problems of pathogenesis of obstructive affections of distal regions of the bronchial tree are under consideration. PMID- 2586041 TI - [Calcium antagonists (finoptin and senzit) in the treatment of cerebrovascular disorders]. AB - Finoptin and sensit produced a favourable effect in the treatment of 290 patients with initial manifestations of deficient blood supply to the brain, encephalopathy attended by circulatory disturbances and ischemic brain insult. Changes in the systemic and cerebral hemodynamics were more pronounced in middle aged and elderly patients suffering from hypertension or its combination with atherosclerosis. PMID- 2586042 TI - [Onset of hypertensive disease and cerebral insult]. PMID- 2586044 TI - [Dynamic thermal imaging in the diagnosis of neurocirculatory dystonia]. PMID- 2586043 TI - [Comparison of the effectiveness of treatment with diverse doses of cinnarizine of patients with circulatory encephalopathy]. AB - A single-dose cinnarizine (25 and 75 mg) was compared to its course administration (75 and 225 mg/day) in 35 patients with circulatory encephalopathy. Upon a 3-fold increase in conventional doses, there appeared more profound clinical, vasomotor cerebral and functional cerebral effects as evidenced by EEG and neuropsychological tests. PMID- 2586045 TI - [Myocardial infarct during prodromal period of hepatitis B]. AB - The paper is concerned with cases of myocardial infarction arising in prodromal period of HBsAg-negative virus hepatitis B. Both diseases ran gravely, fatal outcomes came quickly due to advancing subacute hepatitis. The discussion covers underlying pathogenic mechanisms. Further research is thought necessary. PMID- 2586046 TI - [New approaches to the treatment of single metastases in the liver]. PMID- 2586047 TI - [Determination of components of blood kallikrein-kinin system during therapy of patients with peptic ulcer]. PMID- 2586048 TI - [Characteristics of diagnosis and surgical treatment of giant gastroduodenal ulcers]. AB - Out of 1364 patients operated on in the Central Research Institute for Gastroenterology for ulcer, 130 (9.53%) appeared to have giant gastroduodenal lesions. The latter were gastric in 59 patients (more than 3 cm in diameter), duodenal in 71 (more than 2 cm in diameter). Surgical treatment of the giant ulcers is a valid therapeutic measure in view of frequent complications, uneffective conservative treatment, common recurrences. Billroth I gastrectomy was performed in 2 patients. Billroth II gastrectomy in 110 with additional bilateral subdiaphragmatic or selective vagotomy in 8 cases, Roux' operation in 2 patients. Gastroenteroanastomosis was established in 16 cases of inflammatory infiltrate, disturbed gastric evacuation, no evidence of hemorrhage from the ulcer; in 15 cases of truncal bilateral subdiaphragmatic vagotomy. Lethality reached 3.07% (4 patients), which is a relatively low rate achieved due to appropriate preoperative preparation and early surgical intervention. PMID- 2586049 TI - [Significance of the initial status of the patient for the effectiveness of laser therapy in peptic ulcer]. AB - An association of 8 signs characterizing pretreatment condition of patients with duration of gastroduodenal ulcer healing was statistically evaluated for 220 patients subjected to endoscopic laser therapy. The duration of the mucosal healing correlated with initial diameters and depth of the lesion, stage of its reverse transformation, clinical pattern. It is established that prognosis of laser therapy effectiveness based on original clinico-endoscopical evidence is feasible. PMID- 2586050 TI - [Conservative treatment of postvagotomy disorders]. AB - Drug and spa conservative treatment of postvagotomy aftereffects has been reviewed. The analysis covers the use of enzymes, cholinergic blocking agents, cyproheptadine hydrochloride, amitriptyline hydrochloride, L-Dopa, diphenoxylic acids and opioids in dumping syndrome; benzohexonium and metoclopramide in gastrostasis; diphenoacids and opioids in postvagotomy diarrhea. Oral and external use of mineral water and mud applications proved most beneficial spa treatment modalities. PMID- 2586051 TI - [Effectiveness of lysenyl-forte treatment in acromegaly and hyperprolactinemia syndrome]. AB - Lysenyl-forte, a derivative of polysynthetic ergot alkaloids, producing a dopaminergic and antiserotoninergic action was employed to treat acromegaly and prolactin hypersecretion in 11 and 71 patients, respectively. Clinical effect was established basing on a complex of clinical, x-ray, neuro-ophthalmologic and hormonal evidence. Acromegaly treatment proved efficient: 7 patients (63%) showed partial relief of clinical signs, reduced STH blood level. Out of 48 patients with prolactinemia a response was registered in 34 (71%): a more than 50% decrease in prolactin concentration, normal levels of the hormone in 35% of the patients. A menstrual cycle recovered, galactorrhea diminished, 2 women got pregnant. A positive effect was noticed in management of 13 sterile men with prolactin hypersecretion, in 6 patients with idiopathic prolactin hypersecretion, in 4 women with primary hypothyrosis and galactorrhea. Compared to parlodel, lysenyl was not superior in the frequency of side effects, though was inferior in clinical effectiveness. The drug is recommended for wide-scale use. PMID- 2586052 TI - [Clinico-biochemical parallels in diverse forms of primary hyperparathyroidism]. AB - Altogether 184 patients with bone, renal or mixed hyperparathyroidism (HPT) presenting primarily were examined for blood levels of parathyroid hormone and indirect indicators of parathyroid function. None of the indices (calcium concentration, phosphorus level, serum activity of acid and alkaline phosphatase, oxyproline excretion with urine, etc.) was changed. The commonest biochemical signs of primary HPT were hypercalcemia, hypersecretion of parathyroid hormone, hyperoxyprolinuria. Biochemical indices deviations occurred more often and were more profound in bone primary HPT and parathyroid adenomas. PMID- 2586053 TI - [Significance of immunologic tests in the evaluation of treatment results in subacute thyroiditis]. AB - The authors suggest that the prognosis of subacute thyroiditis may be based after treatment on the immunity state. It was revealed that T- and B-lymphocyte as well as nonspecific defence disorders in treated patients with subacute thyroiditis promote more frequent recurrences or hypothyrosis and autoimmune thyroiditis in comparison with patients whose immunity was slightly involved or not involved at all. PMID- 2586054 TI - [Characteristics of the responses of the sympathoadrenal system in cosmonauts undergoing prolonged cosmic flight on the Saliut-7 orbital station]. AB - Sympathico-adrenal activity of cosmonauts was studied before, during and after 211- and 237-day flights on the Salyut-7 station. During flight blood and urine samples were drawn, collected and stored using a Plasma-01 unit. Blood was withdrawn from two crewmembers on flight days 217-219 by the physician-cosmonaut and brought to the Earth in a frozen state. After the 211-day flight the sympathico-adrenal system showed stimulation of the hormonal component and inhibition of the transmitter component on the recovery day as well as activation of the transmitter component and metabolic changes during the subsequent recovery period. On days 217-219 of the 237-day flight blood catecholamines slightly increased while their renal excretion remained unchanged and their metabolite excretion decreased. All the parameters under study increased significantly during the recovery period. These observations give evidence that the sympathico adrenal system was not activated on flight days 217-219 and was significantly stimulated during the recovery period after 211- and 237-day flights. PMID- 2586055 TI - [The possibility of using cerebral evoked potentials in the diagnosis of fatigue in flight personnel]. AB - The applicability of brain evoked potentials to the detection of pilot fatigue was investigated in simulation studies. During landing that followed a 10-hour flight acoustic evoked potentials (AEP) to sound stimuli (clicks), that were indifferent and irrelevant for pilots in terms of their professional work, were recorded. In averaged AEPs, the components N1 and P2 (90 and 175 ms latent periods, respectively) showed highest stability. In response to stimulation the NIP2 (peak-to-peak) amplitude decreased significantly (on the average by 24.5%) when compared to the preflight level. This can be accounted for by the fact that in the state of fatigue man's capability to perceive and process information declines. From the physiological point of view, this change can be associated with the system that supports piloting functions on the dominant basis as well as with response inhibition to an irrelevant signal based on the negative induction mechanism. This finds expression in a lower amplitude of the major components of averaged AEPs. PMID- 2586056 TI - [Work capacity and space-time organization of cerebral biopotentials in operators against a background of rhythmic light interference]. AB - The effect of light 12 Hz stimulus on the productivity of operator's functions and intercentral integration of neocortical systems was studied in terms of biopotential space-time parameters. EEGs from 8 neocortical areas were recorded in 18 subjects playing an electronic game with a computer (simulated operator's function). A microcomputer Electronika-60 was used for automatic analysis of EEG (spectral-coherent analysis) and operator's efficiency. Light 12 Hz stimulus caused a significant (36%) decrease of operator's productivity (p less than 0.05). In the case of light flickering the density of biopotentials corresponding to the light stimulus frequency increased significantly (30-52%) (p less than 0.05). Coherence of this frequency grew by 17-40%. However, in the 6-8 Hz band the spectral density and coherence of biopotentials of the frontal, motor and parietal areas decreased by 16-21% and 14-23%, respectively (p less than 0.05). Light effects produced disorders in interhemisphere asymmetry. Changes in the spectral parameters of motor areas of the left and right hemispheres and disturbances of interhemisphere interaction were detected. It is assumed that the resistance of the motor control system to light stimulus during operator's activity depends on the resistance of space-time integration of functionally important areas to the synchronizing effect of light interference. PMID- 2586058 TI - [A complex approach to modeling the functional status of a human operator based on the theory of fuzzy sets]. AB - At present the man-operator acting as part of an automatic system experiences ever increasing physical and emotional stresses which makes it highly important to know how to measure reliably his functional state (FS). It is generally recognized that the FS is of systemic nature but the system concept has not been adequately investigated by experiment. The FS evaluation is usually reduced to one of the FS levels. The FS concept is replaced with the concept of the state of bodily functions. It is claimed that the FS can be better explored and estimated with the aid of mathematical models which represent it as a complex psychological event produced by interactions of all psychophysiological systems, operator's activities and his attitudes to them. This paper discusses an FS model which describes the FS from the systemic point of view and helps an investigator to test his hypotheses and heuristics. The model is hierarchic. Its first level is determined by models of such elements of the man-machine system as activities, psycho-physiological transformations, psychological transformations, object of monitoring and control, information system. Such models can be used to evaluate and predict the quality of the function of the above elements in relation to their inherent tasks. The second level of the FS model is associated with its complex evaluation as a systemic formation based on potential interactions (links) between elements. PMID- 2586057 TI - [Psychological preparation of operators for activity under conditions of prolonged overload]. AB - The purpose of the study was to explore the possibility of training subjects on how to work as operators and to perform simultaneously anti-G manoeuvres. It was experimentally demonstrated that such skills are required to increase operator's efficacy when exposed to sustained +Gz acceleration. The results can be used in psychological training of operators to be exposed to sustained acceleration. PMID- 2586059 TI - [Status of the lipid peroxidation system in the tissues of rats following a 7-day flight on the Kosmos-1667 biosatellite]. AB - Rats flown for 7 days on Cosmos-1667 were for the first time used to measure antioxidative enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase), lipid peroxidation products (diene conjugates, malonic dialdehyde, Schiff bases) and tocopherol. Enhanced lipid peroxidation in the heart was completely compensated by activation of antioxidative enzymes. The content of all lipid peroxidation products measured in the liver increased; this was accompanied by a decrease of glutathione peroxidase and an increase of superoxide dismutase activities. It is suggested that lipid peroxidation was activated in response to altered gravity. PMID- 2586060 TI - [The electrolyte balance of the blood in dogs exposed to multiple +Gz overloads]. AB - Experiments of the series were carried out using 7 noninbred dogs. In the first series, the animals were exposed to + GZ acceleration of increasing value once or twice a week during 5 months. Each exposure continued until distinct cardiac arrhythmias were seen in ECG. Two weeks after the onset of exposure the dogs displayed hyponatremia and higher K-Na coefficient and two months later they showed hyperkalemia and hypermagnesemia which led to a 1.5 G increase of acceleration tolerance. In the second experimental series, the animals exhibited a beneficial effect of hypermagnesemia on circulation parameters and frequency of cardiac arrhythmias in response to a single + GZ exposure. These observations have demonstrated that electrolyte balance plays an important part in the development of adaptation to sustained acceleration. PMID- 2586062 TI - [Characteristics of the oculo-vestibulomotor interaction during experimental asymmetry of the labyrinth]. AB - Eye and head coordination in response to trigger and predictive patterns of the gaze fixation reaction was investigated in 19 healthy men under normal conditions and during unilateral monopolar stimulation of the labyrinths. Transient changes in movement coordination and asymmetry of velocity and amplitude characteristics of oculomotor components which deteriorated regulation of search-information reflexes were detected. Changes in the regulation of eye and head movements in response to experimental asymmetry of labyrinths were followed by short-term visual symptoms of the scillopsia type. This was a result of changes of the gain coefficient in the system of ocular, vestibular and motor interaction. It is postulated that labyrinthine asymmetry is one of the mechanisms of sensory mismatch underlying somatomotor discoordination. PMID- 2586061 TI - [Characteristics of the binding by serum albumin of fatty acids and products of their peroxidation during intensive muscular work]. AB - The ability of serum albumin to bind polyunsaturated fatty acids and products of their peroxidation in long-distance cyclists was investigated during their recovery period. In response to high workloads well trained athletes, when compared to lower class cyclists, showed a significant decrease of partial portions of linoleic, arachidonic, eicosapentaenic and other fatty acids. These findings indicate that albumin plays an important part in the transport of fatty acids and lipid peroxidation products as one of biochemical components of metabolic transformations in the course of adaptation to high workloads. PMID- 2586063 TI - [A study of the otolithic membranes of the saccule and utricle of the guinea pig]. AB - By scanning electron microscopy the otolith membranes of the sacculus and utriculus of adult guinea-pigs were examined. The spatial arrangement of otoconia was found to differ from the standard scheme. New forms of imperfect otoconia were detected. Differences in morphological parameters of otoconia in the labyrinthine structures were revealed. Factors responsible for the development of imperfect otoconia on the otolith membrane are described and their relation to the potential changes in the sensitivity of otolith receptors is discussed. PMID- 2586064 TI - [The effect of somatotropin on the healing of skin wounds under hypoxic conditions]. AB - Using cytological, histological, histochemical and histoautoradiographic methods, it was demonstrated that skin recovery in the hypoxic state can be stimulated by somatotropin (STH). STH was shown to stimulate wound healing at every stage: cell migration to the injured area was accelerated, microbial phagocytosis and proliferation of epithelial and connective tissue cells were activated. This led to faster granulation and epithelialization of the wounded surface. The de novo formed epithelium showed a higher activity of succinate dehydrogenase and the granulation tissue - a higher activity of alkaline phosphatase. The hormone treatment reduced destruction of cell elements, newly formed vessels and fibrous structures of the wound which was caused by the hypoxic effect. PMID- 2586066 TI - [Differential criteria of tolerance of a blow to the head for the purpose of certifying protective devices]. PMID- 2586065 TI - [Artificial mineralization of desalinated drinking water using salt tablets and powders]. AB - This paper presents data on the biological role of most macro- and trace elements contained in potable water and emphasizes the necessity of enriching it with mineral components. A profound study of the effect of water desalinated by various methods demonstrated that its salt composition should be standardized with respect to the optimal, allowable and threshold levels of mineralization. The dosage of salt and trace element supplements should be strictly controlled and therefore methods of artificial water mineralization should be thoroughly developed. One of the advanced methods is water conditioning by its supplementation with salt tablets. The purpose of the present investigation was to modify the salt composition of Aquasol tablets in accordance with the new requirements and to perform experiments to investigate the possibility of their enrichment with various calcium salts. The results obtained were used to produce Aquasol-2 tablets that help to improve organoleptic properties of desalted water and to enrich it with physiologically important macro- and trace elements. PMID- 2586067 TI - [Predicting the effect on man of linear and angular impact accelerations]. PMID- 2586068 TI - [Analysis of methods of presenting information to the operator in the process of control]. PMID- 2586069 TI - [Gas chromatographic identification of saturated alcohol groups in hygienic studies]. PMID- 2586070 TI - [Feeding of the crew of the Saliut-7 orbital station]. AB - This paper presents physiological and hygienic evaluations of the food supply of Salyut-7 crews in normal conditions, simulation and actual flights of various duration (211, 150, 237, 165 and 126 days). The examinations have shown that the diets used have provided satisfactory health conditions and good nutritional status of the crewmembers. PMID- 2586071 TI - [Mechanisms of drug resistance of Escherichia isolated from cosmonauts]. PMID- 2586072 TI - [The rate of glycolysis and glycogenolysis in the skeletal muscles of rats in the period of readaptation following 30 days' hypokinesia]. PMID- 2586073 TI - [Principles of evaluating the quality of completed scientific works and the degree of introduction of their results]. PMID- 2586074 TI - Delayed rectifier potassium current in dissociated bullfrog primary afferent neurons. AB - Cultured bullfrog dorsal root ganglion cells were voltage-clamped in the whole cell configuration. The classical delayed rectifier potassium current (IK) was separated from other ionic currents. Tetraethylammonium (1-50 mM) depressed the amplitude of IK in a concentration-dependent manner, a complete block occurring with 30 mM. With the concentration of potassium ions in the superfusate at 20 mM, the reversal potential of IK amounted to about -30mV. IK was activated between 30 and +70 mV. The half activation of IK occurred at +15 mV. The amplitude of IK was increased e-fold with 13.6 mV depolarization. The time constant of IK de activation was shortened with membrane hyperpolarization (tau congruent to 4 ms at -100 mV). Finally, reciprocal time constant (tau -1) of the de-activating IK was increased e-fold with congruent to 13 mV hyperpolarization. It appears that the properties of IK in amphibian afferent neurons are comparable to those which have been observed with respect to the IK of the squid giant axons (Hodgkin and Huxley, 1952). PMID- 2586075 TI - An autopsy case of breast carcinoma with prominent lipid-secretions in the metastatic foci. AB - A 70-year-old woman was treated with a simple mastectomy followed by a course of 5000 rad to the breast and chemotherapy with 5-fluorouracil for breast cancer. About 15 months later, the patient died of widespread metastases. An autopsy revealed no recurrent cancer in the breast. The metastases were seen in bones (sternum, ribs and spine), pleura, spleen, uterus, ovaries, small intestine, adrenal glands, and lymph nodes (hilar, periaortic and mesenteric). Histologically, the resected tumor was a solid-tubular carcinoma with an infiltrative growth pattern. At autopsy, the tumor cells in the metastatic foci contained an abundance of lipids in the cytoplasm, while the tumor cells in the primary tumor contained small amounts of lipids. PMID- 2586076 TI - Esophageal invasion by an upper gastric cancer: retrospective evaluation and prognosis. AB - From 1975 to 1984, 894 patients with gastric cancer were operated on in the Department of Surgery at Kurume University School of Medicine. Of these, 86 (10%) had upper gastric cancer invading the esophagus. The 86 resected tumors were divided into two groups according to the surgical approach, thoraco-abdominal or abdominal. Twenty-three (27%) were resected through the abdominal approach and 63 (73%) were resected by the thoraco-abdominal approach. The overall positive mediastinal lymphnode metastasis rates for the 55 patients who underwent mediastinal lymphnode dissection by the thoraco-abdominal approach were 22% for differentiated type and 37% for undifferentiated type. The positive mediastinal lymphnode metastasis and the correlation to the extent of esophageal cancer invasion were observed at a minimal 7 mm distance from the esophago-gastric (E-G) junction for the undifferentiated type, and 2.2 cm for the differentiated type. Sixteen patients with cancer invading the esophagus were radically resected by the abdominal approach with an overall survival rate of 39%, while 48 were resected by the thoraco-abdominal approach with a 5 year survival rate of 40%. The 86 resected tumors were further subdivided into two groups according to the year of surgery. From 1975 to 1979, the abdominal approach was employed in 36% and the thoraco-abdominal approach in 64% of the surgeries, with an overall curative resection rate of 47%. However, from 1980 to 1984, the abdominal approach was employed in only 17% and the thoraco-abdominal approach in 83% of the surgeries and the curative resection rate increased to 59%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2586077 TI - Gastric operations in patients with hepatic cirrhosis following endoscopic sclerotherapy. AB - Three patients with hepatic cirrhosis who had undergone gastric operations following endoscopic sclerotherapy were retrospectively reviewed. One patient had undergone total gastrectomy for gastric cancer and two had Hassab and Tanner operations for gastric and esophageal varices. All patients were recovering with no complications related to the operations and were free of disease for 2 years, postoperatively. When esophageal varices are found in combination with an upper gastric cancer that requires total gastrectomy, endoscopic sclerotherapy for esophageal varices is contraindicated because severe esophageal injuries may be induced by the sclerosing agent. The Hassab and Tanner method is useful for esophageal and gastric varices after sclerotherapy. A repeat endoscopic sclerotherapy should be performed after this operation. PMID- 2586078 TI - A case of interstitial pneumonia antedating rheumatoid arthritis. AB - We describe a case report of an interstitial pneumonia in which pulmonary involvement of the both lower lobes mimicked idiopathic interstitial pneumonia (IIP) or bronchiolitis obliterans organizing pneumonia (BOOP). Its appearance antedated clinically apparent rheumatoid arthritis by one month and a half. PMID- 2586079 TI - [Dialysis and kidney transplantation]. PMID- 2586080 TI - [Protection for nosocomial infections with hand hygiene]. PMID- 2586081 TI - [Care of organ donors]. PMID- 2586082 TI - [The treatment of vocal cord paralysis using collagen]. PMID- 2586083 TI - [Naloxone]. PMID- 2586084 TI - [Cases, clinical aspects and therapy of retinal detachment]. PMID- 2586085 TI - [Current aspects of hormonal contraception]. PMID- 2586086 TI - Intravenous streptokinase therapy for acute myocardial infarction in a community hospital: effect on ventricular function and mortality. AB - Streptokinase can dramatically impact upon management of myocardial infarctions in community hospitals. When given by experienced personnel during the first six hours after onset of symptoms, streptokinase is associated with a high patency rate, improved left ventricular function, and reduced mortality. Careful screening of patients results in a low complication rate with infrequent serious bleeding. Streptokinase should be utilized in those hospitals without cardiac catheterization facilities, but in light of the relatively high incidence of recurrent pain (15.8%), transfer of stable patients to a facility with a catheterization laboratory should be carried out within 24 to 72 hours. As approximately 60% of patients will require PTCA, CABG, or both, diagnostic cardiac catheterization should be considered in all patients unless there are other mitigating factors. PMID- 2586087 TI - Schizophrenia: promising new directions in South Carolina. PMID- 2586088 TI - Dynamic auscultation. PMID- 2586089 TI - Access to online information: the hardware connection. PMID- 2586090 TI - Into the fray: the community hospital treatment of acute myocardial infarction. PMID- 2586092 TI - Confirmation of noise exposure levels by analysis of the audiometic data in long service underground train drivers. AB - The results of 40 audiograms from otologically normal long-term underground train drivers were compared with the predicted values published by the National Physical Laboratory tables (Robinson and Shipton, 1977). The age-corrected hearing threshold levels were plotted as an arithmetic probability at varying frequencies and compared with the corresponding predicted distributions. The results indicate that London Transport Underground train drivers are subjected to a noise level of less than 85 dB(A)LEQ(8 h), which substantiates the surveyed noise levels. PMID- 2586091 TI - Ethylene oxide sterilizer use and short-term symptoms amongst workers. AB - We surveyed training, the use of protective devices, personal and environmental exposure levels and self-reported short-term health complaints amongst 165 health care workers (response = 76 per cent) using ethylene oxide (EtO) sterilizers in 27 hospitals in the province of Alberta, Canada. Data were collected via self administered questionnaires. Personal and environmental sampling was carried out during site visits to 18 hospitals. Although no detectable levels of EtO were found in environmental samples, over half of the respondents stated they could smell EtO at work. While sampling results never revealed concentrations above the provincial 15 min time weighted average short-term exposure limit (STEL; = 50 p.p.m.), personal exposure concentrations and the use of portable sterilizers were positively associated with short-term symptoms such as irritations of the mucous membranes and skins (P less than 0.05). PMID- 2586093 TI - Substance abuse--a suitable case for testing? PMID- 2586094 TI - Forever amber? PMID- 2586095 TI - Comparison of reported workplace morbidity in 8-hour and 12-hour shifts in one plant. AB - A retrospective study of the minor morbidity diagnoses of 775 workers during two 10-year periods was undertaken. During the first, they worked an 8-hour rotating shift, during the second, a 12-hour shift system. Data were abstracted from well kept medical records from the plant medical department. Illnesses and symptoms indicative of stress-related complaints were abstracted. By age-sex standardization and the calculation of morbidity ratios and confidence intervals, it was shown that the introduction of the 12-hour shift system was accompanied by a statistically significant fall in the incidence of stress-related complaints such as headaches, gastrointestinal upsets and alcohol-related complaints. No reduction was found in the incidence of other illness complaints, considered to be unrelated to stress. Similar but even more marked reduction in the incidence of stress symptoms was found in a cohort of 247 workers who had 10 years of experience in each shift system. PMID- 2586096 TI - Monumental masons: lead and other hazards of an old trade re-visited. AB - A survey of lead exposure amongst gravestone inscription writers was undertaken in 12 firms of monumental masons in London and one in the East Midlands. The mean blood lead concentration in the 25 men studied was 35 micrograms/dl, with six workers exceeding 40 micrograms/dl. The four highest levels were 49, 57, 78 and 89 micrograms/dl respectively, indicating that substantial occupational exposure to lead was occurring. The men were unaware of the risks of lead exposure and the importance of not smoking or eating in their workshops. The stonemasons understood the hazards of granite stone dust, but an unexpected and common finding was an unacceptably high exposure to marble dust. PMID- 2586097 TI - Role of PGF2 alpha in the superior mesenteric artery-induced shock. AB - The role of PGF2 alpha in circulatory shock of intestinal origin was investigated in anesthetized dogs by measuring PGF2 alpha levels in superior mesenteric vein, right ventricle, aorta, and femoral vein during superior mesenteric artery occlusion-induced shock by comparing the circulatory effects of exogenous PGF2 alpha injected into either the superior mesenteric or the femoral vein and by inhibiting of prostanoid synthesis with indomethacin. Release of the superior mesenteric artery occlusion caused a dramatic decrease in mean arterial blood pressure; an increase in mean portal venous pressure, and more than fivefold increases in plasma PGF2 alpha levels in superior mesenteric vein, right ventricle, and aorta. In spite of the decreased mean arterial blood pressure, postocclusion blood flow in the mesenteric artery did not fall below preocclusion values. Indomethacin in itself, significantly reduced plasma PGF2 alpha levels as well as intestinal blood flow and increased mean arterial blood pressure in animals without superior mesenteric artery occlusion. Furthermore, indomethacin attenuated the magnitude of postocclusion hypotension and completely prevented PGF2 alpha production during superior mesenteric artery occlusion shock. Exogenous PGF2 alpha 10 micrograms/kg injected into the superior mesenteric or femoral vein produced hypotension or hypertension, respectively. When PGF2 alpha was injected into the superior mesenteric vein, the plasma level of PGF2 alpha in the aorta was similar to that observed during superior mesenteric artery occlusion shock, whereas PGF2 alpha injected into the femoral vein gave a significantly higher concentration. Pulmonary metabolism of PGF2 alpha was significantly reduced in shock. The present results suggest that PGF2 alpha released by intestinal tissues might play an important role in shock caused by intestinal ischemia. PMID- 2586098 TI - Active uptake of amino acids by the urinary bladder epithelium of rat, rabbit, and dog. AB - Through a series of experiments employing tissue fragments incubated in vitro together with labeled substrates, it was observed that the tight urinary bladder epithelia of rat, rabbit, and dog possess the capacity of an active accumulation of amino acids against a concentration gradient. This uptake is saturable in the presence of sodium, is sodium-dependent, and is inhibited by ouabain. In comparison with other tissues, this phenomenon of active uptake is strikingly resistant to anoxia. The direction of uptake is from blood to lumen across the basolateral epithelial membrane. The induction of hyperplasia in the bladder epithelium of dogs very significantly increased the uptake of amino acids. Further studies should confirm the presence of this phenomenon in the human bladder. PMID- 2586099 TI - Biochemical, biomechanical, and physical changes in the skin in an experimental animal model of therapeutic tissue expansion. AB - Biochemical, biomechanical, and physical changes occurring in the skin during tissue expansion have been studied using an animal model in which a Silastic expander was inserted into the peritoneal cavity. Forty-eight Sprague-Dawley rats were divided into four groups to be studied at 4, 8, 16 and 32 days after expansion. In the experimental animals (6 per group) the expander was inflated by a single injection of 120 ml of saline. Sixteen hours prior to sacrifice each animal received a single injection of tritiated proline. Sixteen days after expansion both the specific activity and the total content of hydroxyproline in the skin were significantly elevated in experimental animals. Intrinsic skin tension increased dramatically at the time of inflation but fell almost to control values at the end of 32 days. Skin thickness, initially decreased, returned to normal by the end of the experiment. There were no significant differences in breaking strengths between skin from experimental and control animals. Skin surface area, initially increased by stretching at the time of inflation, increased further between Days 0 and 8, possibly as a result of stress relaxation combined with enhanced remodelling of connective tissue macromolecules, and again from Days 24 to 32. We conclude that, during tissue expansion, there is a net accumulation of collagen in the skin and that this allows the local cellular environment to return to normal with respect to pressure and/or tension. PMID- 2586100 TI - Effect of hypoproteinemia on blood volume recovery after moderate hemorrhage in conscious splenectomized dogs. AB - Hypoproteinemia is generally considered to form a threat to blood volume homeostasis. In conscious splenectomized dogs we studied whether severe hypoproteinemia, in the presence or absence of edema, would compromise the early recovery of blood volume after moderate hemorrhage (congruent to 25%). Hypoproteinemia, achieved by 10 days of repeated plasma exchange and a low protein diet, did not induce a fall in steady-state blood volume. The interstitial colloid osmotic pressure decreased, an adaptive response probably playing a major role in this maintenance of blood volume. Within the first 2 hr after hemorrhage blood volume recovered by about 30% of the hemorrhaged volume. This early recovery of blood volume was enhanced rather than impaired in hypoproteinemia, in particular in the presence of edema. Since circulating protein did not increase within this 2-hr period, acute fluid attraction occurred through transcapillary influx of interstitial fluid. Chronic hypoproteinemia apparently enhances this fluid attraction. This may be explained by the low interstitial fluid oncotic pressure and fluid expansion, thus by those very factors directed to maintain blood volume in hypoproteinemia. PMID- 2586101 TI - The nude mouse as a model for the study of human pancreatic cancer. AB - The purpose of this study was to characterize an in vivo model of human pancreatic cancer suitable for chemotherapy and immunotherapy studies. In this study we report a 2-year experience in growing the MIA PaCa-2 (CRL 1420) human pancreatic cancer cell line in 92 adult (8 weeks old) and 256 young (3-6 weeks old) nude mice. Ten million tumor cells were transplanted into orthotopic (duodenal lobe of the pancreas) and/or heterotopic positions (hepatic and subcutaneous) and data on operative mortality, effect of total body irradiation (TBI), tumor growth kinetics, and survival are presented comparing the two age groups. Operative mortality was due to anesthetic intolerance which was higher in the young mouse population (13.4% versus 5.7%). Adult mice withstood TBI (500 rad) without mortality but young mice were highly sensitive to radiation damage and their maximum tolerated dose (LD50) was 425-450 rad. Subcutaneous tumors grew significantly more often in young compared to adult animals (97.9% versus 69%) and this finding was not affected by TBI (96.9% versus 75%), though tumors did appear more quickly after TBI. An average of 14.7 +/- 2.8 days was required for the subcutaneous tumors to become macroscopically apparent in the adult population compared with 3.1 +/- 0.8 days in the young mice. The largest subcutaneous tumor diameter 28 days following tumor implant averaged 9.3 +/- 0.6 mm in the young animals and 5.5 +/- 1.7 mm in the adult population (P less than 0.01). Treatment of young mice with human recombinant interleukin-2 (IL-2) (10,000 Units twice a day for 28 days) produced a 27% decrease in tumor growth. This effect was abolished by prior irradiation of the young mice with 375 rad TBI. Pancreatic tumor growth also occurred more consistently in young than in adult animals (91.2% versus 64.3%) and irradiation did not affect pancreatic tumor take in either group. Occasionally intrapancreatic tumor growth was associated with liver metastases in animals that were killed after 28 days (17.8% in young and 22.2% in adult animals). However, when more than 45 days elapsed before sacrificing the animals, the incidence of hepatic metastases increased to 57.1%. This was slightly less than the incidence of hepatic lesions found after direct injection of cancer cells into the liver by portal vein injection (71.4%). Direct extension of tumor into surrounding tissues was common with frequent involvement of the duodenum (83.7%), kidneys (30.6%), and other intraabdominal organs (43.9%). Survival was significantly longer in adult compared to young mice.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2586102 TI - Future possibilities for psychiatry. PMID- 2586103 TI - High-risk behaviors for AIDS among heterosexual alcoholics: a pilot study. AB - A total of 51 (34 men and 17 women) heterosexual alcoholic inpatients were assessed with respect to their engagement in high-risk behaviors for HIV infection and AIDS. Results indicated that a subset of the subjects engaged in frequent and diverse high-risk sexual activities, often had several different sexual partners over a 6-month period, frequently used drugs during sexual activities and sometimes used drugs intravenously. The frequency of high risk behaviors was similar for men and women, but minority subjects engaged in higher levels of high-risk behaviors than did whites. Both age and educational level were inversely related to behavioral risk for HIV infection. Although the current findings are limited due to sample size and representativeness, the results indicate that future research needs to focus on high-risk behaviors for HIV infection among alcoholics, with more attention directed toward prevention and intervention strategies. PMID- 2586104 TI - A macro-level fetal alcohol syndrome prevention program for Native Americans and Alaska Natives: description and evaluation. AB - Presented here are a detailed description and outcome evaluation of a comprehensive, macro-level Fetal Alcohol Syndrome prevention program for Native Americans and Alaska Natives. The program was designed to provide native communities throughout the United States with the knowledge, skills and strategies to initiate primary, secondary and tertiary prevention measures on their own. The key to the program was the training of a cadre of trainers/advocates in all local Native American and Alaska Native communities served by the Indian Health Service. These people were then supported and assisted in their efforts through a variety of means. Evaluation results of knowledge gained indicate that the local trainers had substantial success in imparting FAS information to a variety of audiences (prenatal groups, school children and community groups). Further, the evaluation samples also indicate that the knowledge was retained by the groups over time (2-4 months) and that there may have been some general diffusion of knowledge among peers in local communities. This program is presented in the hope that it will be replicated and improved upon by similar programs using this model as a base. PMID- 2586105 TI - Reproducibility of ethanol elimination rates in long-sleep and short-sleep mice. AB - Ethanol metabolism was measured in long-sleep (LS) and short-sleep (SS) mice on two occasions separated by 1 week to test for repeatability. Mice were injected intraperitoneally with either 1.5 or 4.0 g/kg ethanol and the linear decline of blood ethanol level was measured. The parameters measured in each animal were linear ethanol elimination rate (EER), peak blood ethanol level, volume of distribution and Widmark ratio (r). Reproducibility was assessed using two statistical methods, paired t tests and Pearson correlations. Paired t tests indicated good reproducibility since the two replicate determinations did not differ significantly from each other. The other widely used indicator of reproducibility, the correlation coefficient (Pearson r) between the two measurements, was nonsignificant in almost every case, indicating poor reproducibility. This occurs because the range of values of EER is fairly narrow; thus, an individual is likely to fall anywhere within that narrow range from one day to the next, and the rank ordering of the individuals may not be maintained. Although parameters such as EER and volume of distribution appear to be reproducible for populations, they may have little or no utility as covariates in genetic analyses of individual differences in response to ethanol. PMID- 2586107 TI - Expectancy set, self-reported expectancies and predispositional traits: predicting interest in violence and erotica. AB - To investigate the role of alcohol expectancies in predicting postdrinking behavior, two studies were conducted. In Study 1, an instrument assessing alcohol expectancies was devised for later use in prediction. Factor analyses with split sample validation confirmed 3 factors (11 total items): disinhibition, aggression and sexuality. In Study 2, expectancies, Buss-Durkee hostility and Mosher sex guilt were assessed in a preexperimental questionnaire session. In a subsequent drink administration session, an expectancy set manipulation led subjects to expect alcohol or to expect tonic. To assess postdrinking behavior, interest in violent, erotic and violent-erotic materials was measured unobtrusively using an ad lib slide-viewing task. Consistent with the hypotheses, expectancies in conjunction with trait hostility significantly predicted violence viewing and violent-erotica viewing for expect alcohol, but not expect tonic controls. Moreover, after variance due to hostility was accounted for, expectancies predicted violence viewing significantly and violent-erotica viewing marginally. These findings provide modest support for the proposition that preexisting alcohol expectancies mediate between the effects of expectancy set and postdrinking behaviors. Once activated by perceived alcohol ingestion, these expectancies can shape postdrinking behaviors. The findings also underscore the need for further experimentation aimed at clarifying the interrelationships between alcohol expectancies and expectancy set. PMID- 2586106 TI - Spousal violence among alcoholic women as compared to a random household sample of women. AB - The purpose of this study is to examine the relationship between spousal violence and women's alcoholism problems. This study compares two samples: (1) 45 alcoholic women selected from local treatment agencies and Alcoholics Anonymous groups and (2) 40 nonalcoholic women selected randomly from households. Two-hour interview schedules were administered to both samples. The Conflict Tactics Scale was used to assess spouse-to-woman violence. Alcoholic women were found to have higher levels of spouse-to-woman negative verbal interaction, moderate violence and severe violence as compared to the household women. Multivariate analyses revealed that spouse violence scores were strong predictors of type of sample. This was true even after controlling for presence of alcohol problems in the spouse, income, parental violence, parental alcohol problems and changes in parental family. These findings suggest that alcoholism treatment programs should screen for spousal violence among women alcoholics and that victims of spousal violence should be screened for alcohol-related problems. PMID- 2586108 TI - Factors associated with the problem-engendering use of substances by young men. AB - The responses of 786 young men (mean [+/- SD] age = 18.66 +/- 1.60)-294 substance abusers, 422 putative normals and 70 nonsubstance-abusing psychiatric outpatients -to the 36 items that comprise the Substance Abuse Proclivity (SAP) Scale were intercorrelated and the resulting 36 x 36 item intercorrelation matrix was factor analyzed by the method of principal factors. Three factors were extracted and rotated to oblique simple structure. These factors, each of which was well defined and readily interpretable, were labeled Extroversion, Rebelliousness and Self-Pity. PMID- 2586109 TI - Familial transmission of alcohol use: I. Parent and adult offspring alcohol use over 17 years--Tecumseh, Michigan. AB - A sample of 420 three-member sets of father, mother and adult offspring was drawn from a list of respondents from two rounds of a longitudinal health study in Tecumseh, Michigan. Parents' self-reported drinking practices in 1960 were compared with those of their adult offspring 17 years later in 1977. A positive association between the drinking level of parents and their adult offspring was evident; however, this association varied according to: (1) the drinking level of the parent, (2) the gender of the offspring and (3) the gender of the parent. There is a tendency for offspring to drink abstemiously (i.e., abstain or drink low volume) when their parents were life-long abstainers. High-volume drinking by adult offspring was associated with the parents' same drinking pattern, especially among daughters. Throughout the spectrum of drinking, sons' drinking was more similar to fathers' drinking level than to mothers'. The relationship between one parent's drinking and his/her offspring's was dependent upon the drinking status of the other parent. These data support the hypothesis that parents' drinking patterns may influence the drinking patterns of the offspring as adults. PMID- 2586110 TI - Concepts of alcoholism among whites, blacks and Hispanics in the United States. AB - This article describes agreement with tenets associated with the disease concept of alcoholism among whites, blacks and Hispanics in the U.S. population. Data were obtained from a multistage probability sample of the household population of white, black and Hispanic adults aged 18 years and over residing in the 48 contiguous states. The response rate was 73% for whites, 76% for blacks and 72% for Hispanics. Results show a widespread support for the notion that alcoholism is a disease, independent of ethnicity. However, 40% of the whites, 62% of the blacks and 60% of the Hispanics who agree that alcoholism is an illness also agree that the alcoholic is a morally weak individual. PMID- 2586111 TI - Intracerebral microdialysis: I. Experimental studies of diffusion kinetics. AB - Intracerebral microdialysis is a brain perfusion technique in which a tubular, semipermeable membrane perfused with a physiological solution is implanted into a selected brain region. Molecules in the extracellular space diffuse into the perfusate and may be recovered and their concentration determined. Hence, the level of substances such as neurotransmitters may be monitored, and the response to different treatments may be studied. The technique also allows for administration of substances locally to the region of the brain surrounding the perfused tubular membrane. Basic principles of the microdialysis technique are described, and the results from methodological experiments are examined. It is concluded that there is a direct linear relation between the concentration of a molecule in the medium surrounding the dialysis membrane and the concentration measured in the collected perfusate. Relative changes of molecular concentration in brain extracellular space may be calculated even when the molecular diffusion rate is unknown. In addition, a method is presented for calculating the real concentration of a substance in the extracellular space from its concentration in the perfusate. Applied in striatum of rat brain using microdialysis in vivo, the average extracellular concentration of the following substances is estimated to be: substance P, 0.9 nM; dopamine, 1 microM; and dihydroxyphenylacetic acid, 0.05 mM. PMID- 2586112 TI - Intracerebral microdialysis: II. Mathematical studies of diffusion kinetics. AB - The kinetics of intracerebral microdialysis are studied mathematically. In the microdialysis technique, a tubular membrane that is permeable to diffusion is implanted in the brain and perfused with an artificial cerebrospinal fluid. Molecular diffusion causes substances in the brain to enter the flowing perfusate. The perfusate is collected outside the brain and the content of various substances is determined. The mathematical problem of diffusion through the porous brain tissue into the flowing perfusate is formulated. Solutions for the concentration distributions in the brain and in the perfusate are derived. It is found that the factor limiting the transport is the diffusion through the brain and not through the membrane. A theoretical expression for the recovery ratio is also obtained. This ratio may be used to infer the extracellular concentration in the brain from the concentration in the collected perfusate. PMID- 2586113 TI - Neurological damage in a cardiopulmonary arrest model in the rat. AB - In view of the interest in cerebral protection in the framework of cardiopulmonary arrest (CPA), we assessed the neurological damage in a CPA model in the rat. CPA was induced in anesthetized Wistar rats by discontinuation of the jet ventilation and intracardiac injection of KCl. The animals were resuscitated after a CPA of either 7 min, 10.5 min, or 14 min. Six rats were used as nonischemic controls. All nonischemic rats survived, whereas in the resuscitated rats the 7-day survival rate decreased with increasing CPA duration. In the resuscitated rats, the neurological score was worse than in the control rats, and the score after 10.5-min CPA was worse than after 7-min CPA. Seizures were observed in 68% of resuscitated rats. Histopathological evaluation revealed moderate but selective neuronal necrosis in the hippocampus of all ischemic rats, and no cortical necrosis. However, neither the occurrence of seizures nor the extent of neuronal necrosis was related to the CPA duration. We conclude that in this model survival rate, neurological score, occurrence of seizures, and histopathological assessment can be used to evaluate neurological damage, although the contribution of other organ failure to these effects cannot be excluded. PMID- 2586114 TI - The potential of epicardial activation mapping in isolated hearts for the assessment of arrhythmogenic and antiarrhythmic drug activity. AB - In isolated rabbit hearts perfused according to the Langendorff technique, the pathway and time course of the epicardial activation process were studied by means of computer-assisted epicardial potential mapping, using a matrix of 256 unipolar AgCl electrodes (1 mm spatial and 0.25 msec temporal resolution). Activation time of each electrode was calculated (point of time of fastest negative intrinsic deflection). From the activation times of the surrounding electrodes, the direction and velocity of activation for each electrode were calculated, thereby allowing construction of an epicardial vector field. Furthermore, breakthrough points (BTPs) were determined as the earliest activated electrodes in a given region. Vector-field orientation and BTP localization were compared under different conditions during perfusion with Tyrode's solution or during drug treatment. Thereby, we determined the similarity of the vector fields (two vectors were considered to be identical if not differing by more than 5 degrees) and the percentage of BTPs with changed localization, referred to the total number of BTPs. For verification of the method we treated the hearts with ouabain (0.2 mumol/l) and observed progressive decline in vector-field similarity from 32% down to 14%, resulting in arrhythmia. Concomitantly, the percentage of BTPs with identical localization decreased from 81% to 50%. These changes could be reversed by additive treatment with 10 nmol/1 verapamil. From these results we conclude that arrhythmia is preceded by a state of deteriorated epicardial activation pattern (prearrhythmia), which can be quantitatively evaluated and used for detection of preventive antiarrhythmic drug action. PMID- 2586115 TI - An improved method to correct the QT interval of the electrocardiogram for changes in heart rate. AB - The adequacy of the Bazett formula to correct for heart rate-induced changes in the QT interval of the electrocardiogram has been frequently questioned. In the present study, a simple linear equation was derived, which in anesthetized dogs corrects more adequately for changes in heart rate than the Bazett formula. Regression analysis of experimental data yielded the following equation: QTc = QT - 0.087 (RR - 1000) = QT - 87 (60/HR - 1). The reliability of this equation was investigated in experiments on anesthetized dogs with different cardioactive drugs with a known mechanism of action. PMID- 2586116 TI - Complete repair of pulmonary atresia, ventricular septal defect, and severe peripheral arborization abnormalities of the central pulmonary arteries. Experience with preliminary unifocalization procedures in 38 patients. AB - From 1982 to 1987, 38 consecutive patients with pulmonary atresia and ventricular septal defect underwent staged unifocalization procedures in preparation for final intracardiac repair of the anomaly. Thirty-six patients had concordant visceroatrial, atrioventricular, and ventriculoarterial connections. A central pulmonary artery confluence was present in 19 patients and absent in the remaining group. All patients with central pulmonary arteries had inadequate peripheral pulmonary arterial arborization. Systemic collateral arteries were present in all 38 patients. The objectives of the unifocalization procedures were the interruption of extracardiac sources of pulmonary arterial blood flow, the restoration of segmental, lobar, and pulmonary arterial confluence, the replacement of missing central pulmonary arterial branches, and the creation of a central, accessible source of pulmonary arterial blood flow. A total of 54 unifocalization procedures were performed in the 38 patients. These procedures included 85 permanent connecting anastomoses, 15 temporary anastomoses to the ascending aorta, 13 angioplasty procedures, and 15 modified Blalock-Taussig shunts. Three patients died after unifocalization (two early and one late). By the end of the study, eight patients were still waiting for further unifocalization procedures or angiographic assessment. Four patients were rejected for further surgical treatment because of persistent, uncorrectable defects of the pulmonary arterial arborization pattern. Twenty-three patients underwent complete intracardiac repair with two deaths (one early and one late). Postrepair, intraoperative right ventricular/left ventricular systolic pressure ratio after complete surgical repair ranged from 0.4 to 1.0 (mean = 0.63, standard deviation = 0.14). At the end of follow-up, 21 survivors of complete repair were free of significant symptoms. Unifocalization procedures designed to improve the pulmonary arterial arborization pattern of patients with pulmonary atresia and ventricular septal defect with or without central pulmonary arteries can prepare a significant number of these patients for successful intracardiac repair of the anomaly. PMID- 2586117 TI - Transannular cryoablation of ventricular tachycardia. Surgical technique and results. AB - Intraoperative mapping and cryoablation of ventricular tachycardia was achieved without ventriculotomy in seven patients, who are a subgroup of the 80 patients undergoing map-directed ablation of ventricular tachycardia over a 9-year period. There were four male and three female patients. Their mean age was 53.6 +/- 24.1 years. Coronary artery disease was present in five patients, and two patients had idiopathic ventricular tachycardia. The mean preoperative ejection fraction was 42.4% +/- 13.6%. The mean number of ventricular tachycardia morphologies was 1.7 (range 1 to 3). Epicardial mapping was obtained intraoperatively in all seven patients and endocardial data in five of seven patients (71.4%). There were no hospital deaths and no early or late spontaneous recurrence of clinical monomorphic ventricular tachycardia. Nonclinical monomorphic ventricular tachycardia was inducible in two patients postoperatively and both were treated with procainamide. Death occurred late after operation in two patients: One death was related to recurrent nonclinical VT at 8 months and one at 3 months was due to carcinoma of the stomach. These results suggest that the transannular approach is feasible in selected cases, especially when computerized mapping systems with endocardial balloon electrode arrays can be used. PMID- 2586118 TI - Chemotherapy, radiation therapy, and resection for carcinoma of the esophagus. Long-term results. AB - From May 1980 to May 1984, preoperative chemotherapy (mitomycin C and 5 fluorouracil) was added to radiation therapy in patients with potentially operable squamous cell carcinoma of the esophagus. Of 129 patients observed, 122 were followed up until death or to the present. Only 33 were able to complete preoperative chemotherapy and radiation and undergo resection. There were 28 men and five women, their ages ranging from 42 to 81 years (average 60 years). There were 22 black and 11 white patients. The location of the tumor was in the middle third in 70% of the patients. Among the 33 patients, the clinical TNM classification was as follows: T1 N0 M0, three patients; T2 N0 M0, 27 patients; T2 N1 M0, two patients; and T3 N0 M0, one patient. The length of the lesions when measurable in the absence of complete obstruction varied from 3 to 17 cm (average 7 cm). The operative mortality rate in this group was 12% (4/33). There was no viable residual tumor in the surgical specimen of the esophagus in 33% (11/33) of those patients completing triple therapy. However, in two of the 11 patients, left gastric nodes contained tumor and in one there was a minute esophageal perforation. The 2-year survival rate was 33% (11/33), and the 5-year survival rate was 15.4% (5/33). Among the 11 patients having 2-year survival, the surgical specimen was normal in six and abnormal in five. Of the five patients having 5 year survival, the surgical specimen was normal in three and abnormal in two. The absence of tumor in the surgical specimen did not appear to confer any better chance for long-term survival. Data were compared to our 1967-1975 series of 75 patients receiving only preoperative radiation and resection. There was no significant difference in survival rates at 2 years (20% [1975] versus 33% [1984], p = 0.2118) or at 5 years (10% [1975] versus 15.4% [1984], p = 0.5796). The addition of preoperative chemotherapy as an adjunct did not result in a statistically significant increase in 2-year or 5-year survival rates. PMID- 2586119 TI - Development of pulmonary arteriovenous malformations after modified Fontan operations. AB - Two patients with complex cyanotic congenital heart disease and without previous Glenn anastomosis underwent modified Fontan operations. Postoperatively, pulmonary arteriovenous malformations developed that resulted in cyanosis from significant intrapulmonary right-to-left shunting. These malformations were detected by pulmonary angiograms and contrast echocardiograms. Pulmonary arteriovenous malformations may be a major cause of late clinical deterioration in patients treated with modified Fontan operations. PMID- 2586120 TI - The efficacy of blood cardioplegia is not due to oxygen delivery. AB - Twenty-seven canine hearts instrumented with ultrasonic dimension crystals underwent simultaneous determination of stroke work and myocardial oxygen consumption during incremental volume loading on right heart bypass before and 30 minutes after 2 hours of cardioplegic arrest at 10 degrees C. Three cardioplegic solutions were used: Hematocrit values were 17.0% (group I), 8.2% (group II), and 0% (group III). In all groups the slope of the linear stroke work versus end diastolic volume relationship, a measure of contractility, was unchanged after ischemic arrest. However, the myocardial oxygen consumption for basal metabolism was increased an average of 25.5% after arrest with plasma (group III). Since the plasma concentration in all three groups was identical, and the oxygen available to the hearts during ischemia was the same in groups II and III, the efficacy of blood-based cardioplegic solutions cannot be attributed to a plasma component or to the greater oxygen-carrying capacity of the red blood cell. Future studies should attempt to identify the salutory entity of the red cell responsible for preservation of myocardial oxygen consumption efficiency. PMID- 2586121 TI - Adenosine cardioplegia. Adenosine versus potassium cardioplegia: effects on cardiac arrest and postischemic recovery in the isolated rat heart. AB - Adenosine is a potential cardioplegic agent by virtue of its specific inhibitory properties on nodal tissue. We tested the hypothesis that adenosine could be more effective than potassium in inducing rapid cardiac arrest and enhancing postischemic hemodynamic recovery. Isolated rat hearts were perfused with Krebs Henseleit buffer or cardioplegic solutions to determine the time to cardiac arrest and the high-energy phosphate levels at the end of cardioplegia. Cardioplegic solutions contained adenosine 10 mmol/L, potassium 20 mmol/L, or adenosine 10 mmol/L + potassium 20 mmol/L and were infused at a rate of 2 ml/min for 3 minutes at 10 degrees C. Both time taken and total number of beats to cardiac arrest during 3 minutes of cardioplegia were reduced by adenosine 10 mmol/L and adenosine 10 mmol/L + potassium 20 mmol/L when compared with potassium 20 mmol/L alone (p less than 0.001). Tissue phosphocreatine was conserved by adenosine 10 mmol/L when compared with potassium 20 mmol/L, being 7.1 +/- 0.2 (mumol/gm wet weight (n = 7) and 6.0 +/- 0.3 mumol/gm wet weight (n = 5), respectively (p less than 0.05). Postischemic hemodynamic recovery was tested in isolated working rat hearts. After initial cardiac arrest, the cardioplegic solution was removed with Krebs-Henseleit buffer at a rate of 2 ml/min for 3 minutes at 10 degrees C, and thereafter total ischemia was maintained for 30 or 90 minutes at 10 degrees C before reperfusion. Adenosine 10 mmol/L enhanced recovery of aortic output when compared with potassium 20 mmol/L or adenosine 10 mmol/L + potassium 20 mmol/L, the percentage recovery after 30 minutes of ischemia being 103.0% +/- 4.4% (n = 6), 89.0% +/- 5.8% (n = 6), and 86.6% +/- 4.3% (n = 6), respectively (p less than 0.05 for comparison between adenosine 10 mmol/L and potassium 20 mmol/L). Thus adenosine cardioplegia caused rapid cardiac arrest and improved postischemic recovery when compared with potassium cardioplegia and with a combination of these two agents. PMID- 2586123 TI - Right ventricular myocardial protection through intracavitary cooling in cardiac operations. AB - In an attempt to protect the right ventricle, we designed and tested a closed cooling system that circulates cold saline through a double-lumen, balloon-tipped catheter positioned in the right ventricular cavity. Fourteen sheep were randomly assigned to two groups. In group A (n = 7), the right ventricular cooling catheter system was used in addition to coronary cardioplegic perfusion and systemic hypothermia for myocardial protection. Group B (n = 7) served as a control group. In group A, the right ventricular temperatures were significantly lower than those of the control group (16.1 degrees +/- 0.3 degrees C versus 23.9 degrees +/- 0.4 degrees C; p less than 0.0001, Student's t test). The most common temperature range was 12 degrees to 18 degrees C (67.1%, frequency distribution analysis), and 63.2% of temperatures were below 16 degrees C. The catheter system also maintained the temperatures of the interventricular septum at a lower level than those recorded in the control group and prevented septal rewarming, which was significant in group B (from 16.5 degrees +/- 1.5 degrees C to 25.0 degrees +/- 0.9 degrees C; p less than 0.04, Mann-Whitney U test). Left ventricular temperatures were not changed by the catheter system. By better cooling the right ventricle and the septum, the right ventricular cooling catheter system should decrease the prevalence of right ventricular failure and allow more time to safely complete multiple coronary anastomoses in coronary artery bypass graft operations. PMID- 2586122 TI - Distribution of cardioplegic solution infused antegradely and retrogradely in normal canine hearts. AB - The adequacy of retrograde delivery of cardioplegic solution to the right ventricle and interventricular septum is controversial. To address this issue quantitatively, we infused blood cardioplegic solution labeled with radioactive microspheres (15 microns diameter) into the coronary sinus (n = 8 dogs) at a pressure of 51 +/- 1 mm Hg (mean +/- standard error of the mean) to be compared with the same quantity of labeled cardioplegic solution (20 ml/kg) delivered through the aorta (n = 6 dogs) at 97 +/- 7 mm Hg. Both methods of delivery produced cardiac arrest, but retrograde infusion required a significantly longer time to complete the infusion (6.2 +/- 0.8 minutes versus 1.5 +/- 0.1 minutes, p less than 0.01). Greater than 99% of the microspheres passing through the vasculature of the left ventricle were trapped in the left ventricular myocardium with antegrade infusion, and the distribution of the cardioplegic solution was uniform. Antegrade delivery (cardioplegic flow x infusion time) averaged approximately 3.0 to 4.0 ml/gm, except at the apex, where delivery averaged approximately 2.0 ml/gm. With retrograde infusion, 93% of the microspheres perfusing the left ventricle were trapped and delivery of the cardioplegic solution was not uniform. In the anterolateral free wall, delivery of cardioplegic solution averaged between 1.5 and 2.9 ml/gm (p less than 0.001 compared with antegrade) and only 0.6 to 0.8 ml/gm in the posteroseptal region of the basal left ventricle (p less than 0.001 compared with the antegrade group and anterolateral samples of the retrograde group). In the middle portion of the right ventricle, antegrade trapping of microspheres was 99% and delivery of cardioplegic solution averaged approximately 2.0 ml/gm. With retrograde delivery, only 16.5% (range 11.8% to 26.0%) of the microspheres passing through the right ventricular vasculature were trapped in the right ventricular myocardium, which indicates that substantial shunting had occurred. Corrected for the high shunt fraction, retrograde delivery of cardioplegic solution to the middle portion of the right ventricle averaged only 0.5 ml/gm (p less than 0.01). Retrograde delivery to the atrial septum and right atrium was also low. Because retrograde delivery of cardioplegic solution was markedly nonuniform, we conclude that inadequate cardioplegic delivery to the middle portion of the right ventricle and posteroseptal portion of the left ventricle could result with cardioplegic infusion through the coronary sinus. PMID- 2586124 TI - Deoxyribonucleic acid ploidy pattern of cardiac myxomas. Another predictor of biologically unusual myxomas. AB - A group of patients with cardiac myxoma who have a heritable syndrome involving skin myxomas, endocrine tumors, and lentiginosis--the complex of myxomas, spotty pigmentation, and endocrine overactivity--has been described previously. Patients with the complex had cardiac myxomas at an early age (average, 26 years) with frequent multiple myxomas (53%) and recurrent cardiac myxomas (22%); however, no histologic differences were noted when these tumors were compared with sporadic cardiac myxomas. In the present study, deoxyribonucleic acid flow cytometric analyses of 35 cardiac myxoma specimens were correlated with clinical findings (mean duration of follow-up, 13 years). Among 30 patients with sporadic (nonfamilial) cardiac myxoma, 24 (80%) had a normal (deoxyribonucleic acid diploid) ploidy pattern, and six (20%) had an abnormal (deoxyribonucleic acid tetraploid) pattern. Specimens from each of the five patients with the complex had abnormal deoxyribonucleic acid tetraploid patterns (p = 0.002 compared with the sporadic myxoma group). Further, all four patients who had recurrent cardiac myxoma had an abnormal deoxyribonucleic acid ploidy pattern (p = 0.007 compared with patients with nonrecurrent myxomas). Unlike conventional histologic examination, the ploidy pattern of cardiac myxomas seems to be sensitive for detecting biologically unusual tumors, and a deoxyribonucleic acid tetraploid pattern suggests a high risk of recurrence. PMID- 2586125 TI - Clinical and hemodynamic performance of the Ionescu-Shiley valve in the small aortic root. Results in 117 patients with 17 and 19 mm valves. AB - The Ionescu-Shiley pericardial valve was our bioprosthetic valve of choice between 1981 and 1985 for patients in whom the aortic anulus could not accept a valve larger than 19 mm in outer diameter or in whom the avoidance of warfarin sodium (Coumadin) was important. A series of 117 consecutive patients who received 17 or 19 mm valves for isolated aortic valve replacement or aortic valve replacement combined with coronary artery bypass grafting or other valvular procedures was analyzed. Overall, 74% of the patients were female, with a mean age of 70.9 years and a body surface area of 1.67 +/- 0.19 m2; 92.3% were in New York Heart Association class III-IV, and the operation was urgent or emergent in 46%. The operative mortality rate was 7.7%, with no deaths in patients undergoing isolated elective first-time aortic valve replacement. Mean follow-up for survivors was 2.5 years (10 to 62 months). There were 20 late deaths, of which three were valve related, three were due to sudden death or arrhythmias, and two were due to persistent heart failure. The actuarial survival rate at 5 years was 68%. Clinical follow-up revealed a low incidence of valve-related complications, and 96.4% of survivors were in class I-II. Postoperative echocardiography before hospital discharge revealed a maximum instantaneous gradient of 18.4 +/- 3.0 mm Hg in five patients having a 17 mm valve and 31.3 +/- 12.7 mm Hg in 20 patients having a 19 mm valve. Doppler echocardiography was performed in 22 patients at a mean follow-up of 39.3 +/- 11.7 months. The maximum instantaneous gradient was 25 +/- 17.2 mm Hg for 17 mm and 17.41 +/- 5.4 mm Hg for 19 mm valves at late follow up. The effective orifice area was 0.85 +/- 0.1 cm2 for 17 mm and 1.21 +/- 0.21 cm2 for 19 mm valves. This study defines the normal range of Doppler echocardiographic transprosthetic gradients for the Ionescu-Shiley valve and confirms that low operative mortality and excellent clinical improvement can result from the use of small Ionescu-Shiley valves in elderly patients despite moderate postoperative transvalvular gradients. PMID- 2586126 TI - Wound complications after median sternotomy. Relationship to internal mammary grafting. AB - Case histories of 2582 patients requiring median sternotomy for coronary artery bypass grafting between January 1982 and August 1986 were retrospectively reviewed. Only saphenous vein grafts were used in 230 patients, one mammary artery graft was used in 1626 patients, and both mammary arteries were used in 726 patients. The relationship of potential risk factors and wound complication was evaluated. The overall incidence of wound complications was 0.81%-0.43% in the saphenous vein graft group, 0.49% in the single mammary group, and 1.65% in the bilateral mammary group. Graft type and a number of potential risk factors were analyzed in a logistic regression analysis to determine significant predictors of wound complications. The results indicated that pneumonia, obesity, reexploration, use of the intraaortic balloon pump, and diabetes were significant risk factors contributing to the probability of wound complications. Bilateral mammary grafting was significantly associated with the increased probability of a wound complication developing. Bilateral mammary grafting increased the chance of wound complication nearly five times that of saphenous vein grafting and three times that of single mammary grafting. Mammary artery grafts have been shown to achieve greater long-term patency than saphenous vein grafts, and their continued use is encouraged. However, the potential for increased wound problems should be considered along with other significant preoperative risk factors such as insulin dependent diabetes, chronic pulmonary disease, and obesity. PMID- 2586127 TI - Induction of interleukin-1 production in patients undergoing cardiopulmonary bypass. AB - Systemic reactions resembling inflammation occur in patients undergoing cardiopulmonary bypass. We now report that interleukin-1, an endogenous pyrogen and a key mediator of inflammation, is transiently and consistently generated in vivo by circulating monocytes within hours after cardiopulmonary bypass. Interleukin-1 production was assessed by measuring interleukin-1 functional activity and interleukin-1 beta antigen concentration in cell lysates from monocytes of patients during and after bypass. There was no increase in intracellular interleukin-1 activity during bypass and within the first hours after bypass, possibly because of a suppressive effect of hypothermia on interleukin-1 production, as documented in vitro. Maximal generation of interleukin-1 was observed 24 hours after extracorporeal circulation, concomitantly with the occurrence of a peak in body temperature. The amount of interleukin-1 generated at that time was linearly correlated with the increase in patients' body temperature. The peak in interleukin-1 production followed by 20 hours the peak in complement activation as assessed by determining C3a desArg and C5a desArg concentrations in patients' plasma. These results indicate that interleukin-1 may be involved in the pathogenesis of adverse systemic reactions associated with cardiopulmonary bypass. PMID- 2586128 TI - Acute renal failure associated with cardiac operations. A case-control study. AB - We performed a case-control study to identify risk factors for the development of acute renal failure after cardiac operations. Forty-two cases of acute renal failure were identified in a total of 572 patients who underwent cardiac operations. They were matched with a control population of patients having cardiac operations without acute renal failure. Discriminant analysis performed with preoperative variables revealed preoperative serum creatinine values, concurrent valve and bypass surgery, and age to be significant variables for identifying patients at risk for acute renal failure. The use of these three variables in a discriminant model correctly classified 77% of patients. The addition of intraoperative variables did not significantly improve the ability of the model to correctly classify patients. Acute renal failure was associated with a significant increase in the number of postoperative complications, mortality, and length of hospitalization and intensive care unit stay. PMID- 2586131 TI - Neonatal and infancy time scale for extension into childhood and adulthood. AB - A logarithmic time scale is presented for exposition of clinical events and related data on a unified scale extending from neonatal time into childhood and adulthood. Such a scale preserves time scale proportions but has the advantage for certain applications of featuring early neonatal and infancy events. This type of time base avoids the disadvantages of a crowded and obscured linear scale or an arbitrary and non-unified split time scale. For clinical application all timed events are initially converted to a common unit such as days. A visually comprehensible logarithmic time scale can be derived by plotting the logarithmic scale (labeled in days, base 2) and then establishing conventional calendar interval marks (weeks, months, years) and the data plot points. A simple equation is presented for establishing the time scale graph markers and the plot data points for a logarithmic time scale of any scale axis length. PMID- 2586129 TI - Independent risk factors predicting acute graft rejection in cardiac transplant recipients treated by triple drug immunosuppression. AB - To assess independent risk factors predicting the occurrence of clinically significant acute rejection episodes in the first 6 months after cardiac transplantation, we performed a multivariate stepwise logistic regression analysis. Forty-three recipients, undergoing transplantation between September 1986 and May 1988, were eligible for analysis and received standardized, low-dose triple drug maintenance immunosuppression with cyclosporine, azathioprine, and prednisolone. Immunoprophylaxis was supplemented perioperatively with either a polyclonal (antithymocyte globulin, N = 26) or a monoclonal (OKT3, N = 17) anti-T cell antibody. Investigated, conceivable risk factors comprised recipient and donor age, ischemic time, perioperative anti-T-cell antibody prophylaxis, recipient preoperative status, underlying disease, previous cardiac operation, and histocompatibility parameter (mismatches for HLA-A, HLA-B, HLA-DR, HLA-B+DR, HLA-A+B+DR, and Rh0[D] antigen, HLA-DRw6 positive recipient, and identify for ABO system). Univariate analysis suggested significant influence of the type of antibody used perioperatively (p = 0.0024) and the number of mismatches for HLA A+B+DR (p = 0.0037) and for HLA-B+DR (p = 0.0043). Stepwise logistic regression yielded the number of mismatches for HLA-B+DR (p = 0.0029) and the type of antibody used perioperatively (p = 0.0031) as being highly significant predictors of acute cardiac rejection. Six-month freedom from rejection was 100%, 41%, and 27% for recipients with two, three, and four mismatches for HLA-B+DR and 59% versus 22% for recipients with polyclonal versus monoclonal antibody prophylaxis. Similar to results with kidney transplantation, these results indicate that a poor donor/recipient match for combined HLA-B+DR loci constitutes an independent risk factor for acute graft rejection in low-dose triple drug immunosuppressed cardiac recipients, which stimulates the potential concept of prospective HLA matching. In our experience OKT3 prophylaxis provides significantly less effective prevention of acute rejection than a comparable course of antithymocyte globulin. PMID- 2586130 TI - Reexploration for complications after esophagectomy for cancer. AB - Among 316 patients who underwent resection for esophageal cancer, 23 required reexploration for complications and 10 died. The commonest reason for reexploration was leakage (eight patients). Development of leakage necessitating reexploration was associated with a hospital mortality rate of 75%. Other reasons for reexploration were postoperative bleeding (n = 7), chylothorax (n = 2), burst abdomen (n = 2), diaphragmatic herniation (n = 1), bile peritonitis (n = 1), bowel gangrene (n = 1), and tracheal perforation (n = 1). Definite or presumed technical error could be identified in 18 of the 23 patients requiring reexploration and indicated that the majority of reexplorations were for complications that appeared to be potentially avoidable. When reexploration became necessary, early intervention offered the best chance of survival. PMID- 2586132 TI - Comparison of three cardioplegic solutions during hypothermic ischemic arrest in neonatal blood-perfused rabbit hearts. AB - Inadequate myocardial preservation continues to be an important cause of postoperative morbidity and mortality after pediatric cardiac operations. To investigate methods of improving preservation in neonatal myocardium, we compared three cardioplegic solutions with topical hypothermia during 120 minutes of ischemic arrest in isolated, blood-perfused, neonatal rabbit hearts. Topical hypothermia (15 degrees C) without cardioplegia resulted in 71% +/- 5% recovery of preischemic contractile function. A high potassium (30 mEq/L) cardioplegic solution resulted in a 76% +/- 6% recovery of function, not significantly different from that obtained with hypothermia alone. In contrast, the St. Thomas' Hospital and Hopital Lariboisiere cardioplegic solutions resulted in recoveries of 89% +/- 6% and 88% +/- 7%, respectively, both of which were significantly greater (p less than 0.001) than recoveries obtained with the high potassium solution or hypothermia alone. Thus the cardioplegic solutions used at St. Thomas' Hospital and Hopital Lariboisiere provided excellent protection during 2 hours of hypothermic ischemic arrest in neonatal rabbit hearts and resulted in functional recovery superior to that achieved with hypothermia alone or with the high potassium cardioplegic solution. PMID- 2586133 TI - Regional blood flow distribution during extracorporeal membrane oxygenation in rabbits. AB - To study regional blood distribution during extracorporeal membrane oxygenation, we stabilized three groups of five rabbits each (3 to 5 kg) on venoarterial bypass at a flow rate of 30 ml/kg/min. Albumin aggregates (15 to 30 microns) labeled with technetium 99m were injected into the left ventricle during bypass (ventricle), the perfusion cannula during bypass (cannula), and the left ventricle with no bypass (control). Animals were put to death, organs were removed, and the percent distribution was determined with a gamma camera. The Student Newman-Keuls test was used for statistical comparisons. Distribution to both the heart and brain in the cannula group were decreased from control by 55% and 35%, respectively. Distribution to the brain in the ventricle group was also decreased from control by 39%. Intestinal distribution was elevated above control in the ventricle group by 37%, whereas musculoskeletal distribution was elevated 33% above control in the cannula group. No significant changes were noted for the kidneys, stomach, or liver. These data suggest that overall perfusion of some vital organs may be significantly reduced during low-flow extracorporeal membrane oxygenation, specifically in the case of the heart and brain, which may be deprived of oxygenated blood. PMID- 2586134 TI - Invited letter concerning: pulmonary arteriovenous malformations after modified Fontan operation. PMID- 2586135 TI - Reperfusion after acute myocardial infarction. PMID- 2586136 TI - Invited letter concerning: intraoperative echocardiography. PMID- 2586137 TI - Surgical resection of recurrent metastatic leiomyosarcoma of the heart. PMID- 2586138 TI - Diltiazem in perioperative coronary spasm. PMID- 2586140 TI - The in situ right gastroepiploic artery graft via the superior mesenteric artery. PMID- 2586139 TI - Acute thrombosis of the thoracic aorta diagnosed during life: a rare entity. PMID- 2586141 TI - Pericardio-peritoneal shunt for malignant pericardial effusion. PMID- 2586142 TI - Studies on the relationship between protein kinase C and differentiation of human promyelocytic leukemia cells induced by retinoic acid. AB - We studied the differentiation of acute promyelocytic leukemia (APL) cells in 14 patients with APL. After the induction by retinoic acid (RA) the mature cells rose to 60 +/- 11.8% compared to 0.7 +/- 1% of the control, while the promyelocytes declined to 8.7 +/- 6.4% (93.3 +/- 5.6% in the control group). Protein kinase C (PKC) activity was significantly increased to 149.3 +/- 156.2 pmol/mg per min compared to 47 +/- 40.9 of the control (p less than 0.01). In HL 60 cells, the activity of PKC increased also from 52.3 +/- 35 to 129.2 +/- 64.6 pmol/mg per min (n = 10, p less than 0.01) after the induction of differentiation with RA. If the leukemia cells were pretreated with a kind of PKC inhibitor such as trifluoperazine, the increase of PKC activity was inhibited, and the rate of nitroblue tetrazolium reduction decreased from 89.9 +/- 7.7% to 62 +/- 25% (n = 6, p less than 0.01) and the mature cells reduced from 63.1 +/- 11.7% to 19.7 +/- 12.2% (p less than 0.01). We presumed that the activity of PKC is closely related to the differentiation of human promyelocytic leukemia cells induced by all-trans retinoic acid. PMID- 2586143 TI - Comparison of dexamethasone and lovastatin (mevinolin) as growth inhibitors in cultures of T-cell derived human acute leukemia lines (CEM). AB - Because previous studies have shown that a reduction of cholesterol synthesis is one of the earliest effects of dexamethasone on neoplastic lymphoid cells, a study was made to compare dexamethasone to lovastatin, a specific inhibitor of cholesterol synthesis, which acts on 3-hydroxy-3-methylglutaryl coenzyme A reductase. Two cell lines were used, both derived from human acute T-cell leukemia, one dexamethasone-sensitive (CEM-C7), the other dexamethasone-resistant (CEM-Cl). The results revealed a similar pattern of resistance and sensitivity of both lines to lovastatin, although only the dexamethasone effect was reversed by 1 microM RU 486, the antiglucocorticoid steroid. The cell killing by dexamethasone and lovastatin had the characteristics of apoptosis. PMID- 2586144 TI - Leukaemia and nutrition. I: Malnutrition is an adverse prognostic factor in the outcome of treatment of patients with standard-risk acute lymphoblastic leukaemia. AB - A group of 43 pediatric patients with standard-risk ALL were studied. Thirty seven per cent of them presented with malnutrition at diagnosis. Malnourished children had a significantly worse outcome than well-nourished children. Five year DFS was 83% for well-nourished children (WNC) and 26% for under-nourished children (UNC) (p less than 0.001). Relapses presented more frequently in the bone marrow in UNC than in WNC (56% vs 7%, p less than 0.0001). The doses of maintenance chemotherapy had to be reduced in 68% of UNC and 11% of WNC (p less than 0.005); the doses of maintenance myelosuppressive chemotherapy (6-MP, oral MTX and hydroxyldaunorubicin) received by UNC were approximately 50% of those received by WNC (p less than 0.01). The correlation between malnutrition and compromised treatment was 0.92. Malnutrition might be included as an adverse prognostic factor in acute lymphoblastic leukaemia (ALL). PMID- 2586145 TI - Clinical value of long-term maintenance chemotherapy in 5-year survivors of acute leukemia. AB - We investigated whether long-term follow-up of 5-year or longer survivors of acute leukemia might provide some information concerning cure-oriented chemotherapeutic strategy. By sending a questionnaire form to major medical institutions throughout the country, data of 2202 5-year or longer survivors of acute leukemia was obtained as of 30 June 1988. There were 1607 children and 595 adults. In order to investigate the data further, they were divided into four periods according to the year of diagnosis: before 1969, 1970-1974, 1975-1979 and 1980-April 1983. As regards remission induction regimens, vincristine plus prednisolone (VP) was the most popular in childhood acute lymphoblastic leukemia (ALL) throughout these four periods. In adult acute non-lymphoblastic leukemia (ANLL), daunomycin (DM), cytosine arabinoside (ard-C), 6-mercaptopurine (6MP), prednisolone (STH) (DCMP) or behenoyl ara-C, DM, 6-MP, STH (BH-AC.DMP) was the most popular since the latter half of the 1970s. Both in childhood ANLL and adult ALL, there was no predominant regimen whatsoever. In an analysis of survival curves for the above four periods, each survival plateau for childhood ALL rose over time with statistical significance, reaching over 90% in the 1980s, whereas those for adult ANLL were not so, suggesting that newer ANLL regimens in the 1980s did not play a successful role in cure-oriented therapy. Whether duration of post-remission chemotherapy could be a prognostic factor for these survivors was studied by dividing the duration as follows: less than one year, 1-2, 2-3, 3 5 and more than 5 years. A therapeutic gain, with a cure rate of over 90%, was observed in childhood ALL patients treated with chemotherapy for 5 years or longer. In adult ANLL patients, results were similar with chemotherapy groups of both less than one year and 5 years or longer. This suggests that risk-adapted therapy is an optimal strategy for cure of adult ANLL as well as childhood ALL. PMID- 2586146 TI - Efficient formation of cytosine arabinoside-5'-triphosphate in leukemic blasts of human T-cell acute lymphoblastic leukemia. AB - The potential usefulness of cytosine arabinoside (ara-C) in the treatment of T cell acute lymphoblastic leukemia (T-ALL) was studied by measuring the influx of ara-C into the lymphoblasts and the conversion of ara-C to its triphosphate form (ara-CTP) in lymphoblasts from the bone marrow of eighteen patients of T-ALL. Intracellular accumulation of ara-CTP was 3.5 times greater in T-cell lymphoblasts than in non-T or AML blasts. The increased formation of ara-CTP in T ALL cell may be correlated with the good clinical response of T-ALL patients to the treatment with ara-C in combination with mitoxantrone. PMID- 2586147 TI - Low IL-1 beta production in leukemic cells from progressive B cell chronic leukemia (B-CLL). AB - In vitro production of IL-1 beta by cells from 32 patients with benign monoclonal lymphocytosis of undetermined significance (MLUS) and B cell chronic lymphocytic leukemia (B-CLL) was investigated. Normal B lymphocytes (2 x 10(6)) secreted approximately 5 ng/ml of IL-1 beta during 24 h and approximately ten times more after stimulation with Staphylococcus aureus, strain Cowan 1 (SAC). When patients were studied, a loss of IL-1 beta production was found in leukemic cells from progressive disease. Cells from MLUS patients secreted near normal levels of IL-1 beta and responded to SAC stimulation, whereas cells from patients with progressive B-CLL produced no, or little IL-1 beta, and did not respond to SAC. Loss of IL-1 beta production in progressively growing B-CLL may be related to an increased malignant character of these cells. This is discussed in relation to the immunogenicity of the leukemic cells and their capacity to differentiate. PMID- 2586148 TI - Soluble interleukin-2 receptor released locally as an indicator of central nervous system relapse in adult patients with acute lymphoblastic leukemia. PMID- 2586149 TI - Differential intracellular staining of identified neurones in Locusta with texas red and lucifer yellow. AB - The bright red fluorescent dye, Texas red, is introduced for ionophoretic microinjection in conjunction with the well-known dye Lucifer yellow. Different identified neurones can thus be visualised in two strongly contrasting colours in the same preparation (differential intracellular staining) following their physiological characterisation. Satisfactory results were obtained with electrodes filled with 4% Texas red (sulforhodamine 101 acid chloride; w/v) in 1 M potassium acetate (pH 3.0) and 5% Lucifer yellow (w/v) in aqua dest., respectively. Texas red was injected ionophoretically with pulsed depolarising current (3-10 nA, 500 ms pulses at 1 Hz, 15-30 min) and Lucifer yellow with hyperpolarizing constant current (5-6 nA, 5-15 min). Histological tissue processing was identical for both dyes, the quality of intracellular recordings with Texas red electrodes was similar to that with Lucifer yellow electrodes. Stained neurones could be visualised in both whole-mounts and sectioned preparations. Differential staining of two identified synaptically coupled neurones, a motoneurone and an interneurone, in the mesothorax of Locusta is presented as an illustration for the possible localisation of contact sites at the light-microscopic level. PMID- 2586150 TI - Collection and handling of ultrathin serial sections for 3-dimensional reconstruction. AB - Serial sectioning for 3-D reconstruction requires a highly skilled and experienced individual to collect ribbons of ultrathin sections on formvar-coated grids, and to handle the grids after section collection. A simple method is described for placing ribbons in an orderly serial fashion on formvar-coated grids, by a microtomist with average experience. Prior to sectioning, a wax ledge is prepared on the sloping edge of a glass knife in order to support a formvar coated grid held in a horizontal slot cut in the wax. After a ribbon is formed, the water in the trough is slowly withdrawn to allow the ribbon to settle on the grid. The grids are then placed in an easy-to-make plastic chamber so that the formvar does not get ruptured during drying. The chamber can also be used for staining and storage of grids thereafter. Approximately 4000 sections from mudpuppy retinal cells have been successfully collected using this method. Computer 3-D reconstruction of the individual cells has been done. PMID- 2586151 TI - Long-term cultivation of cryopreserved human fetal brain cells in a chemically defined medium. AB - Conditions for long-term cultivation of human fetal brain cells in a chemically defined medium were established using cryopreserved brain fragments obtained from legal abortions. Tissue of the same gestational age was pooled and the cells cultured in a fully defined medium containing insulin-like growth factors (IGF I and II). Primary cultures were kept for 2-4 weeks and secondary or tertiary cultures could be maintained for 3 months. The cultures were characterized by morphological, electrophysiological and biochemical methods. Glial cells were predominant during the first two weeks of culture. In later stages of cultivation, glial cells diminished in number and most cells were neuronal. Voltage-dependent Na+ channels were recorded from neurons. Biochemical studies indicated that the fetal brain cells contained and secreted immunoreactive somatostatin as well as the tachykinins, substance P and neurokinin A. Cultures grown in IGF II- or nerve growth factor-containing medium expressed increased choline acetyltransferase activity. PMID- 2586152 TI - Serial determinations of regional cerebral blood flow in the rat using simple chronically implanted platinum wire microelectrodes. AB - The ability to reliably obtain serial determinations of regional cerebral blood flow (rCBF) over time in small animals using simple and inexpensively constructed platinum-wire microelectrodes has been investigated. Repeated measurements of local cortical flow were obtained on a daily basis using the hydrogen clearance technique in a group of 18 animals, in each of which, 6 electrodes were chronically implanted. Our studies have shown the simple microelectrodes utilised to give a low variability of results, as well as being well tolerated and provoking minimal tissue reaction even over prolonged periods of time. Under identical steady-state conditions, serial determinations of rCBF were obtained for up to one week, with a maximum variation in mean values of only 12%, a result that compares favourably with the known serial determination error for the technique in the shorter term. PMID- 2586153 TI - Mapping of insect muscle fibres innervated by the same motoneurone by intracellular injection with cobalt dye. AB - A method which allows the intracellular staining of physiologically identified muscle fibres is described. The possible applications of this method have been discussed. PMID- 2586154 TI - A new device for monitoring concentrations of intracellular Ca2+ in CNS preparations and its application to the frog's spinal cord. AB - For monitoring the changes in intracellular concentrations of Ca2+ in vertebrate CNS neurones in situ, we devised an assembly of two quartz-made optic fibres enclosed in a glass capillary. Esterified fluorescent Ca2+ indicator (quin2/AM) was injected into the motoneuronal pool of the frog's spinal cord, and about 60 min later, the assembly was inserted directly into the same region. Ultraviolet light for exciting the indicator was transmitted through one optic fibre, while the fluorescence emitted from the cells was guided to a photoelectric converter through the other fibre. Administration of Ringer's solution containing some stimulant (KCl, excitatory amino acids) through arterial perfusion, evoked both an increase of fluorescence intensity under excitation light of 340 nm wavelength and a decrease under 380 nm light. Electrical stimulation delivered to a dorsal root provoked equivalent responses in fluorescence; this response is known to be an indicator of an elevation in intracellular concentrations of Ca2+. PMID- 2586155 TI - A model of proximal middle cerebral artery occlusion in rat. AB - A highly reproducible model of middle cerebral artery (MCA) occlusion in rat is described. Reproducibility relates to MCA occlusion at its most proximal portion and the surgical approach through a widened foramen ovale, thus avoiding craniotomy and brain retraction. Spontaneous ventilation is maintained, avoiding intubation. Collateral circulation to cortex is preserved, permitting optimal metabolic and pharmacologic studies of the ischemic regions destined for infarction. PMID- 2586156 TI - Investigation of multiple simultaneously active brain sources in the electroencephalogram. AB - We present a method of investigating multiple simultaneously active brain sources that overlap both in space and time in the scalp electroencephalogram (EEG). In order to identify the contributions of the individual brain sources to measured potentials, we applied principal component analysis and various methods of rotating the principal components including a newly developed rotation procedure using frequency criteria. We related the results of these multivariate statistical techniques to a new physical model using multiple current dipoles with fixed anatomical locations and time-varying activities. We thus are able to study 3-dimensional location, time activity and interaction of multiple simultaneously active brain sources in the scalp EEG. PMID- 2586157 TI - Sealing cultured invertebrate neurons to embedded dish electrodes facilitates long-term stimulation and recording. AB - Recently it has become possible to form small networks of synaptically connected identified invertebrate neurons in culture. Using conventional saline-filled glass electrodes, it is difficult to simultaneously stimulate and record from more than 2 or 3 cultured neurons and to perform experiments lasting longer than several hours. We demonstrate that it is possible to overcome these limitations by using planar arrays of electrodes embedded in the bottom of a culture dish. The arrays employ conductive leads and insulation that are transparent, making the dishes compatible with voltage-sensitive dyes and inverted microscopy. Identified neurons from leech Hirudo medicinalis, slug Aplysia californica, and snail Helisoma trivolvis, have been grown on these arrays. Due to their large size (soma diameter 40-200 microns) these neurons form seals over the dish electrodes. Individual electrodes can then be used to stimulate and to record action potentials in the associated neuron. With sealing, action potentials have been recorded simultaneously from many neurons for up to two weeks, with signal to-noise ratios as large as 500:1. We developed and tested a simple model that describes the voltage waveforms measured with array electrodes. Potentials measured from electrodes under cell bodies were primarily derivatives of the intracellular potential, while those measured from electrodes under axon stumps were primarily proportional to local inward Na+ currents. While it is relatively easy to record action potentials, it is difficult to record postsynaptic potentials because of their small size and slow rate of rise. PMID- 2586159 TI - [A check point in nursing management. Surfacing of a management problem as an opportunity for renewed effort for problem solving]. PMID- 2586160 TI - [Questions and answers in nursing management. Difficulties in grasping the daily status of work allocation and implementation of educational programs at an ambulatory department]. PMID- 2586158 TI - [Overhauling of the British medical system and hardship faced by health care personnel]. PMID- 2586161 TI - [A check point in nursing management. Nursing supervisor's personal involvement in research to stimulate interest among the staff]. PMID- 2586162 TI - [Group approach in order to prevent iatrogenic incidents]. PMID- 2586163 TI - [Personality: Ms. Seiko Muramatsu, an organizer of the Home Nursing Research Center]. PMID- 2586165 TI - [Questions and answers in nursing education. Efficacy of the use of personal computers in nursing schools]. PMID- 2586164 TI - [A check point in nursing education: availability of student counseling services and assistance by professional counsellors]. PMID- 2586166 TI - [Questions and answers on clinical training. Nurses' unwillingness to give advice to student nurses]. PMID- 2586167 TI - [Revised nursing curricula: opinions by educational specialists]. PMID- 2586168 TI - [Importance of smiles among nurses and training in proper usage of speech]. PMID- 2586169 TI - [Methods in problem-solving in nursing: a nursing supervisor trying to ease the nurse shortage crisis]. PMID- 2586170 TI - [A survey on nurses' caloric consumption by walking]. PMID- 2586171 TI - [Ultimate in nursing profession. A short essay by a nursing supervisor]. PMID- 2586172 TI - [Clinical training in nursing. 5. Clinical training which can be readily understood by students (2)]. PMID- 2586173 TI - [A report on nursing training. The effect of learning by experience observed through a "class image"]. PMID- 2586174 TI - [Evaluation of nursing planning based on the POS concept in clinical training]. PMID- 2586175 TI - [Man and nursing. "Care" 5. Care in nursing (1)]. PMID- 2586176 TI - [Practice of psychiatric rehabilitation nursing seen in case studies]. PMID- 2586177 TI - [Organization of a new home room for nursing students]. PMID- 2586178 TI - Smoking, leukemia, and lymphocyte mutations. PMID- 2586179 TI - Recombinant erythropoietin failed to correct anemia in Fanconi syndrome. PMID- 2586180 TI - Molecular analyses of chromosome 12 in chronic lymphocytic leukemia. AB - Trisomy 12 is the most common chromosomal aberration in chronic B lymphocytic leukemia (B-CLL). In this study we have investigated trisomy 12 and posed two major questions: (a) What is the origin of the third copy of chromosome 12? and (b) What is the proportion of trisomy 12 cells in malignant clones with this aberration? The origin of an extra copy of chromosome 12 in lymphocytes from patients with B-CLL was studied by the use of probes detecting restriction fragment length polymorphisms on this chromosome. In all six patients that were evaluable, the third copy was derived from a simple duplication of one of the original chromosomes. In none of these patients nor in four patients with two copies of chromosome 12 were losses of the homologue observed. When studying metaphase cells from some CLL patients with trisomy 12, a large proportion of the cells are found to have a normal karyotype. In this study the fraction of normal metaphases was not matched by a similar fraction of cells lacking trisomy 12, as judged by scanning densitometry of hybridization bands. Thus, normal metaphases appear to be derived from a small fraction of easily stimulated probably nonmalignant cells and not from a large second population of malignant cells with a normal karyotype. PMID- 2586181 TI - The leukaemia research fund data collection survey: the incidence and geographical distribution of acute myeloid leukemia. AB - This paper reports on the 2,362 cases of acute myeloid leukemia (AML) accumulated by the Leukaemia Research Fund Data Collection Survey between January 1, 1984, and June 30, 1988 providing the recent geographical distribution and descriptive epidemiology of the AML group of conditions. Statistical approaches to this data set are described. The study shows sex differences in distribution for those aged under 55 years compared to older age groups, with variable male: female incidence in different age bands and a male excess in those over 55 years. A nonsignificant excess of females was noted in those under 5 years. The rates presented for 1984 1986 are higher than those previously described for England and Wales. Statistically significant variation in incidence was seen both between counties and districts. At electoral ward level regression analyses were suggestive of links between AML and higher social class and living close to estuaries. PMID- 2586182 TI - The Leukaemia Research Fund Data Collection Study: descriptive epidemiology of acute lymphoblastic leukemia. AB - This paper reports on cases of acute lymphoblastic leukemia (ALL) recorded by a specialist registry of hematopoietic malignancies. The cases have been diagnosed since January 1, 1984, and originate from certain parts of the United Kingdom. The information is analyzed by age, sex, and area of residence at diagnosis. The age distribution shows a childhood peak but fails to show an adult peak previously reported in literature from abroad. At a broad geographic level the county of Cumbria is shown to display the highest rates of ALL in all ages both in the 3 years of formal analyses (1984-1986) and in the 2 recent years. The administrative districts of Copeland, Sedgemoor, and North Devon also show excesses in all ages with Copeland having the highest SRR and level of statistical significance. This is a new observation for Copeland, the district containing the Sellafield nuclear reprocessing facility in that the high rates are for all ages of ALL. These new data were not considered in earlier official reports about that area. A regression analysis at electoral ward level shows no statistically significant association but excesses of cases, which are mirrored in a larger "all leukemias" data set, occur in wards near estuaries (a new observation) and in the upper socioeconomic groups. PMID- 2586183 TI - Chromosomal and immunophenotypic patterns in T cell acute lymphoblastic leukemia (T ALL) and lymphoblastic lymphoma (LBL). AB - In this study of 33 T cell acute lymphoblastic leukemia (T ALL) and 17 lymphoblastic lymphoma (LBL) patients, no relevant differences between the two groups were observed in clinical characteristics, response to therapy, and survival. We found translocations involving 14q11, 7q35, or 7p15, where T cell receptor alpha and delta, beta, and gamma subunit genes reside, in 20 patients (40%). Most of these translocations were seen with equal frequency in T ALL and LBL, indicating that, in a large proportion, the two diseases are different manifestations of the same lymphoblastic disorder. However, other translocations, such as t(9;17)(q34;q23), occurred only in LBL, perhaps pointing to the existence of subsets of LBLs that are distinct from T ALL. On the basis of karyotype, 50 patients could be classified into three groups: 20 patients with 14q11, 7q35, or 7p15 translocations (group A); 20 with other translocations, and/or deletions (group B); and 10 with normal diploidy (group C). There was no difference in survival time between any two of the three groups. PMID- 2586184 TI - Is health care use changing? A comparison between physician, hospital, nursing home, and home-care use of two elderly cohorts. AB - This study used log-linear survival analysis, and log-rank tests to compare 1) the characteristics of two elderly cohorts; 2) their use of physician, hospital, nursing-home and home-care services over 8.5 years; and 3) physician and bed supplies during the two periods. Both cohorts were similar in health status and in their use of hospital, nursing-home, and home-care resources despite a steady decrease in hospital beds during both periods and a shrinking supply of nursing home beds for the later cohort. Although physician supply increased more rapidly for the first (1971) than for the second (1976) cohort, the later cohort used significantly more ambulatory care than the earlier cohort. Home care appears to substitute for year-to-year variations in nursing-home admissions but not for variations in hospital lengths of stay. PMID- 2586185 TI - The relationship between patients' satisfaction with their physicians and perceptions about interventions they desired and received. AB - This study was designed to determine the relationship between patients' satisfaction with their physician, the types of interventions that patients reported they received, and the congruence between those interventions and the types of interventions they desired. One hundred eighteen symptomatic adult primary-care patients completed questionnaires before and after their respective medical visits. Patients who indicated they received any one of the three nontechnical interventions: education (P less than 0.001), stress counseling (P less than 0.05), and negotiation (P less than 0.01), were significantly more satisfied than those who had not received these interventions. Patient perceptions about receiving technical interventions, i.e., examination, tests, medications, and nondrug therapy, were not related to patient satisfaction. The congruence between patient-intervention desires and perceptions about interventions received generally were not significantly related to satisfaction except for the interaction between receiving a medication and postvisit medication desires (P less than 0.001). A series of multiple regression analyses revealed that, in general, perceptions about nontechnical interventions were better predictors of patient satisfaction than perceptions about technical interventions. PMID- 2586186 TI - The effect of office visit copayments on utilization in a health maintenance organization. AB - This study estimated the impact of a $5 copayment on office visit rates in a health maintenance organization. A quasi-experimental design was used to compare the observed changes in visit rates by state government enrollees between the year before copayments and their first year of copayments with changes between the same time periods for a control group of enrollees without copayments. Visit data for 30,415 state enrollees and 21,633 federal enrollees who were enrolled continuously for at least 12 months before and after the start of copayments were obtained from automated data systems. The introduction of a $5 copayment for office visits resulted in an estimated 10.9% decrease in primary care visits (95% confidence interval (CI): -13.4% to -8.4%) and a 3.3% drop in specialty care visits (95% CI: -15.6% to +9.0%). The effect of copayments on primary care visits by enrollees under 40 years of age was twice as large for females as for males. Copayments also had a significantly greater impact on enrollees who were high users (greater than ten primary care visits) during the year before copayments. The copayment effect was immediate and did not diminish over the 12-month study period. PMID- 2586187 TI - The hidden future supply of foreign medical graduates. AB - The number of foreign medical graduates (FMGs) as reported by the American Medical Association (AMA) has registered increases in recent years far exceeding the Department of Health and Human Services' (DHHS) published forecasts. The DHHS projections of new entrants have been derived from the number of postgraduate year-one positions filled by FMGs. Apparently, the FMG supply is augmented by physicians who enter by other paths. By using AMA data, this study takes the first step in attempting to shed light on the characteristics of these recent FMG additions. It then uses the DHHS model to forecast FMG supply based on a short run continuation of the AMA-reported changes. The paper also forecasts FMG supply assuming that no new foreign national FMGs (FNFMGs) will enter the pool. The analysis suggests that some FNFMGs may be entering this country with visas granted to family members of United States citizens or permanent immigrants and then establishing practices without exiting directly from graduate medical education (GME). Further restrictions on GME participation for FMGs likely are not going to severely curtail FMG entrance into the medical care delivery system. Rather, they will likely restrict their entrance by way of the most traditional route. PMID- 2586188 TI - Interday reliability of function assessment for a health status measure. The Quality of Well-Being scale. PMID- 2586189 TI - [The role of mechanically purified city sewers in the spread of antibiotic resistant bacteria of the Enterobacteriaceae family]. AB - The aim of this study was to evaluate a degree of contribution of mechanically cleansed municipal sewage in a spread in on environment of bacteria of Enterobacteriaceae family with special regard to antibiotic resistant strains. High number of bacteria of Enterobacteriaceae family was found in 1 ml of sewage and the number of antibiotic-resistant bacteria was 0.5-50 X 10(3)/ml. Among the strains tested the resistance to more than one antibiotics was encountered. 78.3% of strains transferred antibiotic resistance to E. coli recipient strain, what indicate a participation of potentially pathogenic bacteria from Enterobacteriaceae family in a spread of antibiotic resistance in a environment. PMID- 2586190 TI - [Selected properties of lactose-fermenting and non-fermenting Salmonella agona strains isolated from specimens from hospitalized infants]. AB - The aim of this study was to compare some of the properties of 28 lactose positive and 28 lactose-negative Salmonella agona strains isolated from faeces of infants hospitalized in the same hospital. Some of biochemical properties, sensitivity to 14 antibiotics and chemotherapeutic agents and sensitivity to bacteriophages used for typing of this Salmonella genus were tested. Results of biochemical examinations revealed that lactose-fermenting strains retain the remaining of Salmonella of subspecies I. Two biochemical features are of particular importance: the ability to ferment lactose on all lactose containing media and a lack of the ability to produce H2S on Kligler medium. These two features differentiate lactose-fermenting strains of Salmonella from non-lactose fermenting ones. Antibiotic sensitivity pattern differed between lactose-positive and lactose-negative strains. Lactose-positive strains showed higher degree of resistance than lactose-negative strains. The differences in resistance were seen in the case of chloramphenicol, doxycycline, gentamicin and tetracycline. Both lactose-positive and lactose-negative strains were sensitive to colistin, neomycin, nitrofurantoin and nalidixic acid. They were resistant to ampicillin, cloxacillin, rifampicin, streptomycin, sulfatiazol and biseptol. Bacteriophage typing revealed that all lactose-negative strains isolated in this study from clinical samples belonged to the same phage pattern V. Lactose-positive strains belonged to two phage types VB and XI. Type VB prevailed. PMID- 2586191 TI - [Migration of Al(OH)3 in the bodies of experimental animals]. AB - The aim of this study was to observe aluminium hydroxide distribution in mice given this substance subcutaneously and intraperitoneally in various concentrations (0.03 mg-0.8 mg of Al3+ per dose). Each experimental group consisted of 5-6 mice of which brain, liver and kidney were isolated after 7, 14, 28, and 35 days after injection. Control group was composed of unvaccinated mice. Sera of animals vaccinated subcutaneously with the following doses: 0.2 mg, 0.4 mg and 0.8 mg were also tested. A distinct accumulation of Al3+ in liver after intraperitoneal injection with a tendency of rising after 28 days of observation was seen. The same was observed in kidneys after subcutaneous injection, especially doses of 0.4 mg Al3+ and 0.8 mg Al3+. The aluminium content in sera was high in an early period of observation only, and subsequently its elimination was fast. PMID- 2586192 TI - [Bacteriocinogenic properties of Staphylococci isolated from the oral cavity]. AB - Two hundred ninety two staphylococcal strains were isolated out of 130 saliva samples taken from children and adults, among which 116 were coagulase-positive and 176 coagulase negative. Bacteriocinogenic activity against Staphylococcus aureus strain Oxford 209P was found in 13 (4.5%) of the strains only. On the other hand, when a set of 15 sensitive staphylococcal strains selected by cross checking was used for the study 260 (89.0%) strains were found to be bacteriocinogenic. It was found that a higher percentage of coagulase-positive staphylococcal strains is sensitive to staphylococcins than of coagulase-negative strains. However, mean zone of inhibition is smaller in the case of former than of the latter strains. It was shown, that in the case of active strains a positive correlation exists between a percentage of coagulase-positive and negative strains inhibited by them and also between a percentage of all inhibited strains and a mean diameter if the growth inhibition zone. Simultaneous occurrence in saliva of two or more staphylococcal strains was found in 106 persons examined. In 93.4% of those cases coexisting strains did not show antagonistic properties: in remaining 6.6% despite of the number of simultaneously existing strains in oral cavity only one strain showed antagonistic properties against the remaining strains. PMID- 2586193 TI - [Piglets as a model for studying the activity of staphylococcal shock syndrome toxin (TSST-1)]. AB - In this study the influence of toxic shock syndrome toxin produced by Staphylococcus aureus on the organism of piglets of Minnesota race is presented. Animals were tested in two groups: conventional and gnotobiotic and they were given the toxin intradermally in two doses 10 and 100 micrograms/kg of body weight. It was shown that piglets are sensitive to the toxin which induced rise of body temperature, various clinical symptoms and in functional changes of several organs as shown by analytical studies. Gnotobiotic animals showed lower susceptibility to the toxin as compared to conventional piglets what suggest a participation of endotoxin in pathologic process. PMID- 2586194 TI - [Studies of the effects of BCG and Corynebacterium parvum vaccines in experimental infection of mice with influenza virus. Foot pad test, splenic indicator and histologic changes in the thymus gland, spleen and lymph nodes]. AB - Evaluation of the influence of BCG and Coparvax on reticulo-endothelial system in mouse was performed. Mice were stimulated i.p. with BCG vaccine and Coparvax vaccine. Spleen index and histological changes in thymus, spleen and lymph nodes were evaluated after 14 days in mice vaccinated with BCG and after 7 days in mice vaccinated with Coparvax. Foot pad test was also performed by giving vaccine into three feet. Tuberculin was injected into mouse foot pad on the day 7th and 14th and a lysate of Coparvax vaccine on the day 7th. Spleen index and foot pad test showed higher values in mice vaccinated with Coparvax than with BCG. Histological changes of thymus, spleen, and lymph nodes showed morphological differences depending on the type of vaccine used. Both preparations were characterized by stimulating effect on reticuloendothelial system, which was much more pronounced after giving Coparvax vaccine. PMID- 2586195 TI - Vascular relaxing effects of bumetanide. AB - Bumetanide reduced basal tension of resting carotid arteries as well as tonic contraction elicited by 36 mM of KCl, KNO3 and 0.1 mM norepinephrine but had little effect on phasic response to norepinephrine and angiotensin II. Bumetanide was much more active against norepinephrine than KCl, KNO3 and its effect was not reduced by propranolol. These findings establish a distinction between bumetanide and the Ca antagonists, which do not affect basal tension but selectively inhibit potassium (K+) contracture. On the contrary, this compound resembles the nitrocompounds in that vascular relaxation does not require the integrity of endothelium but is abolished by methylene blue. These two common traits support the view that the increased synthesis of cyclic GMP secondary to guanylate cyclase activation may be directly involved in the vasodilating properties of the drug. PMID- 2586196 TI - Effects of antidepressants on alcohol-induced gastric mucosal injury in rats. AB - The purpose of the present report is to study the effects of antidepressants such as trimipramine, amitriptyline, maprotiline and mianserin on severe gastric mucosal lesions produced by ethanol in comparison with cimetidine (H2 antihistamine) and dexchlorepheniramine (H2-antihistamine). The percentage of macroscopic mucosal lesions caused by alcohol affects 15% of the mucosal area. But pretreated with cimetidine the affected area was 9.18%, with dexchlorepheniramine 5.01%, with trimipramine 14.46%, with amitripytline 7.94%, with maprotiline 3.8%, and with mianserin 4.07%. Microscopic evaluation reveals that ethanol produces destruction of glandular cells and injures medial and basal layers. All drugs used previously to ethanol produce a decrease of microscopical lesions. A direct relation was found between micro and macroscopical lesions in rats treated with maprotiline, mianserin and dexchlorepheniramine. PMID- 2586197 TI - The influence of amikacin on digoxin uptake by certain rabbit tissues in vitro. AB - The influence of amikacin on digoxin uptake by various rabbit tissues was investigated in vitro. 125J-digoxin was used and radioactivity was counted in a gamma scintillation counter. Amikacin decreases digoxin uptake by the renal tissue and this action is probably due to a displacing effect. On the contrary, amikacin increases digoxin uptake by striated and cardiac muscle. It is suggested that the latter action is due to a vasodilating effect of the aminoglycoside antibiotic that favors the microcirculation of the above tissues. PMID- 2586198 TI - Percutaneous absorption of coumarin, griseofulvin and propranolol across human scalp and abdominal skin. AB - The objective of this study was to investigate the role of the transfollicular pathway in the diffusion process of chemicals through excised human skin in vitro. Skin was obtained from 5 cadavers (3 males, 3 females) within 24 h of death. The age of the subjects varied between 18-77 years. Three radiolabelled drugs, namely 14C-coumarin, 3H-propranolol and 3H-griseofulvin, were studied. The permeation parameters such as flux, lag time, diffusion coefficient and permeability constant were determined across scalp and abdominal skin using the Thomas Diffusion Cell. For all tested substances the flux through scalp skin was higher than across abdominal skin and the lag time was decreased. The differences were statistically significant at p less than 0.05 for coumarin and propranolol. These data suggest that the transfollicular pathway in permeation might have a significant impact on the diffusion parameters for some drugs. Also, in the case of coumarin, permeability seems to be epidermis/dermis-controlled, whereas for griseofulvin and propranolol the Stratum corneum apparently is the permeability limiting barrier. PMID- 2586199 TI - The bioavailability of Tamoplex (tamoxifen). Part 4. A parallel study comparing Tamoplex and four batches of Nolvadex in healthy male volunteers. AB - A randomized parallel design has been validated for the study of tamoxifen bioavailability. Strong evidence was presented for the bioequivalence of Tamoplex 10 mg and four Nolvadex 10 mg preparations. Interbatch differences were of the same magnitude as differences between Tamoplex 10 mg and Nolvadex 10 mg. No in vitro--in vivo relationship could be established. Distribution and metabolism are the dominating factors in tamoxifen pharmacokinetics. PMID- 2586200 TI - Biostin (RU-41740) does not impair antipyrine metabolism in healthy volunteers. PMID- 2586201 TI - GABAergic agents and clonidine attenuate footshock-induced aggression in mice. AB - The effects of gamma aminobutyric acid (GABA), baclofen, and clonidine was studied on footshock-induced aggression in mice. A lower dose (200 mg/kg) of GABA enhanced the aggressive score, while at a higher dose (400 mg/kg) it attenuated the aggressive behavior, the latter effect being reversed both by bicuculline and picrotoxin (PTX). Clonidine (0.5 and 1 mg/kg) enhanced the aggressive score, and the effect of clonidine was reversed by idazoxan. GABA (400 mg/kg) and clonidine (1 mg/kg) significantly reduced the aggressive score in reserpinized mice. Baclofen (5 mg/kg) showed no effect per se in either reserpinized or non reserpinized mice. On concomitant administration of clonidine (0.5 mg/kg) with a subeffective dose of either GABA, baclofen, or diazepam, there was significant reduction in the aggressive score. A modulatory role of GABAergic and noradrenergic systems in footshock-induced aggression is suggested. PMID- 2586202 TI - The effect of naloxone and the kappa antagonist MR 1452 MS on myocardial infarction in rats. AB - The intravenous infusion of naloxone (Nal) (0.17 mg/kg/min) and of the selective kappa antagonist MR 1452 MS (0.07 mg/kg/min) on rats with left coronary artery occlusion was studied. The results demonstrated significant improvement of cardio circulatory parameters, i.e., mean arterial pressure (MAP), heart rate (HR) and cardiac output (CO). The action of Nal is peripheral and central with prevalence of central effect, since its hypertensive effect is due to a rise in total peripheral resistance (TPR) (by 12%), rather than to an increase of CO (by 3% compared to saline-treated rats 20 min postinfarction). The effect of MR 1452 MS is mainly peripheral, since MAP increased due to increased CO (by 5% and by 8% compared to saline-treated animals 20 min and 2 h postinfarction). As a result of increased MAP and CO a reduction of myocardial oxygen deficiency was evident, and the development of cardiogenic shock in Nal- and MR 1452 MS-treated animals decreased by 7% and by 17% 2 and 24 h postinfarction. Reduction of the incidence of early arrhythmias (20 min-2 h postinfarction) by 25% and 16%, respectively, was found. Mortality was significantly reduced in both groups by 8% 2 h postinfarction and by 17% 24 h postinfarction, which suggested a comparable effect of both drugs in cardiogenic shock. PMID- 2586203 TI - Relationship between coronary flow and high energy phosphates in the isolated perfused rat heart, with special reference to the effects of anoxia, iodoacetic acid, and 2,4-dinitrophenol. AB - In Langendorff rat hearts, anoxia increased the coronary flow, concentration of adenosine in the coronary effluent and the tissue level of lactate, and decreased the intracellular oxygen, left ventricular pressure (LVP), heart rate and the tissue levels of adenosine triphosphate (ATP) and creatine phosphate (CrP). In the normoxic heart, an infusion of iodoacetic acid (IAA) (0.1 mg/min) increased the coronary flow, adenosine concentration in the effluent, and decreased ATP and CrP levels, without decreasing the intracellular oxygen. When glucose in the perfusate was substituted for pyruvate, IAA did not produce the pharmacological effects. In the normoxic heart, an infusion of 2,4-dinitrophenol (DNP) (50 micrograms/min) increased the coronary flow, adenosine concentration in the effluent and oxygen consumption, but decreased the intracellular oxygen, LVP and the tissue levels of ATP and CrP, without affecting the lactate level. There was no direct relationship between the coronary flow and the adenosine concentration in the effluent, but there was a close relationship between the increase in coronary flow and the total loss of myocardial ATP and CrP during anoxia, infusion of IAA, or infusion of DNP. These results indicate that the total loss of ATP and CrP from the myocardium (and hence energy state of the myocardium) may be responsible for regulation of coronary flow. PMID- 2586205 TI - [Specialized units and local hospitals: big differences between the length of stay and type of care of mentally disturbed criminals]. PMID- 2586204 TI - Erythrocyte sodium and potassium transport systems during longterm administration of the diuretic xipamide in men. AB - The effects of xipamide on the intracellular concentration and transmembrane fluxes of Na+ and K+ were studied in twenty-four normal sodium-replete or deplete male subjects, using a double-blind study design. After a run-in period on placebo for 1 week on their regular diet, subjects were treated on their regular diet or on a low-sodium diet with either placebo or xipamide 20 mg once a day for 16 weeks. Intra-erythrocyte Na+ concentration was increased during xipamide administration in sodium-replete and deplete subjects, while intra erythrocyte K+ and total intraleukocyte Ca2+ concentrations were decreased. Red cell Na+, K+-cotransport activity was lower in xipamide-treated subjects, while Na+, Li-countertransport activity was increased. No significant effect of xipamide could be demonstrated on ouabain-sensitive 86Rb-uptake or on maximal [3H]-ouabain binding in erythrocytes. PMID- 2586206 TI - [To become a physician in occupational health services--choice, meetings and changes]. PMID- 2586207 TI - [The delegation of the Swedish Medical Society: improved guidance on medical terminology. A continuing support for specialists' examinations]. PMID- 2586208 TI - [Small intestinal transplantation will be an alternative in short bowel syndrome]. PMID- 2586209 TI - [Limit the number of routine preoperative check-ups]. PMID- 2586210 TI - [Non-registered preparations--the way to find information]. PMID- 2586211 TI - [Treatment of vaginal discharge]. PMID- 2586212 TI - [The catastrophic bus accident in Mabydalen. Better disaster planning is needed]. PMID- 2586213 TI - [Magnetic resonance tomography in psychiatry--clear benefits for health care services]. AB - The use of MRI in clinical psychiatry is evaluated on the basis of over four years' experience. Of 931 psychiatric patients examined, 156 were found to manifest pathological cerebral conditions, a frequency of 17 per cent, as compared with 2 per cent (2/101) among apparently healthy controls. The occurrence of intracerebral lesions, with exclusively psychiatric symptoms, is illustrated with case reports. The importance is stressed of early examination with neurodiagnostic imaging techniques in cases of psychiatric disorders where any of the following symptoms or preliminary diagnoses are present: atypical psychiatric features, first episode psychosis, late onset depression, dementia, HIV and other infections in conjunction with psychiatric symptoms, hysteria, and alcohol or drug abuse. The findings suggest MRI to be a useful supplementary diagnostic tool for improving the care of the psychiatric patient, while relieving the burden both on the patient's family and on mental health care resources. PMID- 2586214 TI - [Current research: tumor vaccines]. PMID- 2586215 TI - [The law of compulsory treatment of psychotic, somatically ill patients with HIV 1 infections]. PMID- 2586216 TI - [Cessation of smoking decreases the number of cases with spontaneous pneumothorax and resources can be redistributed]. AB - The incidence of spontaneous pneumothorax has increased during the last fifty years, and recent studies indicate that tobacco smoking increases the incidence approximately tenfold among women and twentyfold among men. Total direct and indirect costs for the community due to smoking-induced spontaneous pneumothorax in Sweden amount to roughly 70 million SEK annually. Were smokers to give up smoking, 70 to 90 per cent of the cases could be avoided. These figures, and the fact that other smoking-induced diseases annually cause at least 10,000 deaths, 1,000 permanent disabilities, and 450,000 days of hospital care in Sweden, constitute formidable arguments in favour of efforts to prevent smoking. PMID- 2586217 TI - Fibroblast growth factor pretreatment reduces epidermal growth factor-induced proliferation in rat astrocytes. AB - Epidermal Growth Factor (EGF) is mitogenic for purified rat astrocytes in primary tissue culture. A combined concomitant treatment by EGF and Fibroblast Growth Factor (FGF) does not reduce the proliferation effect of EGF, however when the astrocytes are pretreated with FGF, their response to an EGF stimulation is reduced by 70%. This inhibition of EGF stimulation by FGF pretreatment is consistent across the EGF dose response curve and perhaps represents a mechanism for local modulation of astrocyte mitogenic effects. PMID- 2586218 TI - Differential effects of the pharmacological manipulation of serotonin systems on cocaine and amphetamine self-administration in rats. AB - The effects of the administration of serotonergic drugs on infusion rates of rats self-administering cocaine and amphetamine on an FR-10 schedule of reinforcement in daily 4 hour sessions were compared. Pretreatment with fluoxetine (2.5, 5, and 10 mg/kg), an inhibitor of serotonin reuptake, significantly decreased rates of responding maintained by amphetamine, but had no effect on responding maintained by cocaine at any of the doses tested. Pretreatment with cinanserin (3, 10, and 17.5 mg/kg), a serotonergic receptor antagonist, decreased rates of amphetamine self-administration at the highest dose tested, and also had no effect on cocaine self-administration. These data suggest a differential sensitivity of cocaine and amphetamine self-administration to pharmacological manipulation of central serotonin systems. They are consistent with biochemical data which demonstrates a negative correlation between the reinforcing potency of amphetamine-like drugs, but not cocaine-like drugs and their potency at serotonin binding sites. PMID- 2586219 TI - Biphasic pattern of hypersensitivity following acute propranolol withdrawal in normal subjects. AB - The effect of abrupt propranolol withdrawal on exercise-induced changes in heart rate and blood pressure was studied in six normal volunteers. Response to exercise was measured on two occassions during propranolol treatment and 1, 2, 3, 4, 5 and 7 days after the last dose of propranolol. Exercise-induced changes in heart rate were significantly lower than control during propranolol treatment (p less than 0.005). Following propranolol cessation, all subjects showed a biphasic pattern of hypersensitivity. Heart rate response was significantly greater than control 2, 3 and 7 days after the last propranolol dose (p less than 0.05) and not significantly different from control 1, 4 and 5 days after the last dose of propranolol. Exercise-induced changes in pulse pressure showed a biphasic pattern similar to the changes in heart rate. PMID- 2586220 TI - Effect of exogenous ascorbic acid intake on biosynthesis of ascorbic acid in mice. AB - The effect of exogenous ascorbic acid intake on biosynthesis of ascorbic acid in mice has been studied. After the mice were on diets containing added ascorbic acid for two months, the activities of ascorbic acid synthesizing enzymes in the mouse liver homogenates were measured using L-gulono-gamma-lactone as a substrate. Exogenous ascorbic acid intake (0.5, 1 or 5% in the diet) was able to increase the concentration of ascorbic acid in the blood and to decrease the activities of ascorbic acid synthesizing enzymes in mouse liver. The results suggest that ascorbic acid synthesis was controlled by local regulatory mechanism or by the concentration of ascorbic acid in the hepatic portal blood. Ingestion of dietary erythorbic acid, a stereoisomer of ascorbic acid, had no effect on the activities of ascorbic acid synthesizing enzymes. PMID- 2586221 TI - Modulation of hepatic glucose-6-phosphate dehydrogenase activity in male and female rats by estrogen. AB - The effect of estradiol-17 beta on the activity of glucose-6-phosphate dehydrogenase was studied in both male and female rats to further characterize the sex differences in the activity of this enzyme. Four groups of intact and castrated rats were implanted subcutaneously with graded doses (2.4, 4.8 and 7.2 micrograms/day) of pelleted estradiol in a physiologically relevant experimental system. After fourteen days the rats were sacrificed and their livers were assayed for G6PD activities. The result indicated that: (i) the enzyme activity was 3-fold higher in normal adult female than in male rats, (ii) low doses of E2 (2.4, 4.8 and 7.2 micrograms/day) increased the activity of G6PD 6-fold in castrated males and over 2-fold in female castrates as well as intact rats (iii) E2 stimulation of G6PD activity appears to be more effective in castrated males than in female rats (IV) sex difference in the activity of G6PD disappeared after treatment with E2 in castrated rats. It is concluded that the activity of G6PD in rats is markedly enhanced by low doses of E2, which appears to be largely responsible for the sex differences in the activity of this enzyme in rats. PMID- 2586222 TI - A sheep model for MPTP induced Parkinson-like symptoms. AB - Administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) causes behaviors reminiscent of idiopathic Parkinson's disease in man and other primates, but development of such symptomology has not been reported to date in other species. We now report a sheep model which responds to administration of low levels of the compound with well defined, apparently permanent symptomology very similar to that seen in primates. Histological examination indicates drug dependent destruction of the substantia nigra which, in sheep, lacks the high levels of neuromelanin present in primates. Following infusion of either MPTP or MPP+, only the metabolite MPP+ was detected in serum with this metabolite demonstrating a very long half life. The rapid disappearance of MPTP suggests that its potency will be directly related to a function of body size and inversely related to heart rate. PMID- 2586223 TI - Quantitative and qualitative heterogeneity in smooth muscle myosin heavy chains. AB - Previous studies have shown that smooth muscle myosin consists of two heavy chains (MHCs) of unequal molecular weight; however, it is not clear whether there are intermuscle, inter- and intraspecies differences in the MHCs. The purpose of these experiments was to quantitatively and qualitatively compare MHCs in different smooth muscles. Extracts of bovine aorta (BAo), dog saphenous vein (dSV) and femoral artery (dFA), and rat aorta (rAo), femoral artery (rFA), carotid artery (rCA), ileum (rGI) and uterus (rUt) were electrophoresed on 5% polyacrylamide-1% SDS gels. All tissues exhibited two MHCs with molecular weights of 207,000 (MHC1) and 204,000 (MHC2) daltons. In all cases the proportion of total MHC made up by MHC1 was greater than that by MHC2. Based on their relative proportions (MHC1:MHC2), the tissues fell into one of three groups: (1) 55:45 - rAo, rCA, dFA; (2) 60:40 - dSV, BAo, rGI; and (3) 65:35 - rUt, rFA. Group 1 differed significantly from group 3 in the proportion of each MHC. One dimensional peptide maps indicated that BAo, dSV and dFA were similar while subtle differences existed between rUt and rAo. Differences between rUt and rAo were also observed in their cross-reactivity to a monoclonal antibody to smooth muscle MHC, confirming the differences seen on peptide maps. These results indicate that there are intertissue and inter- and intraspecies differences in smooth muscle MHCs. The significance of these differences to muscle function remains to be determined. PMID- 2586224 TI - Opioid-like discriminative stimulus properties of benzomorphans in the pigeon: stereospecificity and differential substitution patterns. AB - Pigeons were trained to discriminate the kappa-opioid agonist bremazocine (BREM) or the mu-opioid agonist fentanyl (FENT) from water. During tests of stimulus substitution, FENT and BREM failed to substitute for each other. The (-)-isomers of cyclazocine, pentazocine and ketocyclazocine substituted for the FENT but not the BREM stimulus. The (+)-isomers of these compounds, as well as the isomers of nallylnormetazocine, failed to substitute for either the FENT or BREM stimulus. In FENT- and BREM-trained pigeons, the (-)-isomers of cyclazocine, pentazocine, nallylnormetazocine and ketocyclazocine were more potent than their respective(+) isomers in decreasing rates of responding. These results indicate that in the pigeon there is an isomeric separation of the discriminative stimulus properties of cyclazocine, pentazocine and ketocyclazocine and that the FENT-like stimulus effects of these drugs reside in their (-)-isomers. In addition, the present findings establish further that the classification of the discriminative stimulus effects of mu and kappa opioid compounds in the pigeon differ from those in rat and monkey. PMID- 2586225 TI - Identification of fatty acid amides in human plasma. AB - A family of five long-chain fatty acid carboxamides has been identified and semi quantified in human plasma by GC-MS. One saturated and four unsaturated amides were found. Luteal phase plasma from 16 women was studied, and all five of the amides were found in ten of the subjects, but none in the other six. The structure of these endogenous amides was established by comparing their GC and MS characteristics with those of the synthetic amides prepared by ammonolysis of corresponding long-chain fatty acid acyl chlorides. PMID- 2586226 TI - Metaphit inhibits dopamine transport and binding of [3H]methylphenidate, a proposed marker for the dopamine transport complex. AB - Metaphit, an acylating derivative of phencyclidine, was shown to interact with components of the dopamine nerve terminal in rat striatal tissue. This compound, previously demonstrated to be an irreversible inhibitor at the phencyclidine receptor, was shown in these experiments to irreversibly inhibit synaptosomal [3H]dopamine uptake. It also inhibited binding of [3H]methylphenidate to its recognition site, which is thought to be a subunit of the dopamine transporter. Although the inhibition was due primarily to a reduction in the binding and transport capacity of the systems studied, increases in the apparent KD of [3H]methylphenidate and the Km of [3H]dopamine were also observed. Differences in the behavior of Metaphit and phencyclidine in these dopaminergic systems compared to their effects on the NMDA receptor-linked phencyclidine receptor suggest that Metaphit may be interacting with two distinct molecular sites in the rat striatum. PMID- 2586227 TI - Impact of lemongrass oil, an essential oil, on serum cholesterol. AB - To test the hypothesis that non-sterol mevalonate pathway end products lower serum cholesterol levels, we asked 22 hypercholesterolemic subjects (315 +/- 9 mg cholesterol/dl) to take a daily capsule containing 140 mg of lemongrass oil, an essential oil rich in geraniol and citral. The paired difference in serum cholesterol levels of subjects completing the 90-day study approached significance (P less than 0.06, 2-tailed t-test). The subjects segregated into two groups, one consisting of 14 subjects resistant to the protocol and the other consisting of 8 subjects who responded. Paired differences in cholesterol level at 30, 60 and 90 d for resistant subjects were +2 +/- 6, +2 +/- 7 and -1 +/- 6 mg/dl; paired differences for the responding subjects were -25 +/- 10 (p less than 0.05), -33 +/- 8 (p less than 0.01) and -38 +/- 10 (p less than 0.025), respectively. The paired difference (+8 +/- 4) in the cholesterol levels of six responders 90 days after the discontinuation of lemongrass oil was not significant. PMID- 2586228 TI - Effects of cholestyramine and squalene feeding on hepatic and serum plant sterols in the rat. AB - Hepatic and serum phytosterol concentrations were compared in the rat under basal conditions and during activated cholesterol and bile acid production due to squalene and cholestyramine feeding. Both treatments consistently decreased hepatic and serum levels of sitosterol and campesterol and, unlike esterified cholesterol, esterified plant sterols were not increased in liver during squalene feeding. Serum levels of phytosterols were decreased quite proportionately to those in the liver. The hepatic levels of sitosterol and campesterol closely correlated with each other, but not with cholesterol levels. The percentage esterification of both phytosterols was lower than that of cholesterol. The results indicate that activation of hepatic sterol production leads to depletion of hepatic plant sterols. It is suggested that poor esterification of plant sterols may contribute to this decrease. PMID- 2586229 TI - Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. AB - The role of vitamin E in the protection against iron dependent lipid peroxidation was studied in rat liver microsomes and Triton-dispersed microsomal lipid micelles. In these systems, an antioxidant effect of vitamin E at a physiological ratio to phospholipids could be observed only in the presence of phospholipid hydroperoxide glutathione peroxidase (PHGPX) and glutathione. The rationale of this cooperation is discussed on the basis of the hydroperoxyl radical scavenging capacity of vitamin E and the reduction of membrane hydroperoxides by PHGPX. The scavenging of lipid hydroperoxyl radicals by vitamin E, although inhibiting propagation of the peroxidative chain, produces lipid hydroperoxides from which ferrous iron generates alkoxyl radicals that react with vitamin E almost as fast as with fatty acids. Therefore, only if membrane hydroperoxides are continuously reduced by this specific peroxidase does the scavenging of hydroperoxyl radicals by vitamin E lead to an effective inhibition of lipid peroxidation. PMID- 2586230 TI - The simultaneous separation and quantitation of human milk lipids. AB - A protocol using a dry column method was modified for the extraction of total lipids and the simultaneous separation and quantitation of neutral and polar lipids in human milk. The triacylglycerol, cholesterol, phospholipid and vitamin E contents of the lipid extracts were determined and compared with lipids extracted using a modified Folch procedure. Good precision for the extraction of neutral, polar and total lipids, as well as the different lipid classes, was demonstrated. No significant differences were found between the two methods with respect to the amount of cholesterol, phospholipid, total lipid or vitamin E extracted, thus validating the method as an extraction technique. We discuss the relationship between vitamin E and the three major milk lipids as an indicator of the vitamin's place of origin in the mammary gland. Our findings do not support the idea that vitamin E in mature milk has its original location in the apical membrane. PMID- 2586231 TI - Alpha-oxidation of alpha-hydroxyfatty acids in rat brain. Possible involvement of an alpha-peroxylactone. AB - Combined--but not individual--microsomal and supernatant fractions obtained from rat brains not only consume oxygen but also provoke emission from added chlorophyll. These results are consistent with literature data (Levis and Mead, J. Biol. Chem. 239, 77 [1964]) for trapping of radioactive 14CO2 following addition of alpha-hydroxy-[1-14C]stearic acid. The most plausible explanation for emission is the interaction of chlorophyll with an alpha-peroxylactone. An intermediary alpha-peroxylactone in alpha-oxidation is consistent with other available data (Salim-Hanna, Campa and Cilento, Photochem. Photobiol. 45, 849 [1987]; Campa, Salim-Hanna and Cilento, Photochem. Photobiol. 49, 349 [1989]) and, on chemical grounds, provides a feasible route to the final products. PMID- 2586232 TI - Inhibition and induction of bile acid synthesis by ketoconazole. Effects on bile formation in the rat. AB - The effects of ketoconazole, an antimycotic agent, and metyrapone, an inhibitor of mixed function oxidases, on bile acid synthesis were compared in the rat both in vitro and in vivo. In rat liver microsomes, ketoconazole was much more potent than metyrapone in inhibiting the activity of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the synthesis of bile acids. The I50 values were 0.42 microM and 0.91 mM for ketoconazole and metyrapone, respectively. Intraduodenal administration of ketoconazole caused a rapid, dose-dependent reduction of bile acid synthesis in eight-day bile diverted rats. A single dose of 50 mg/kg reduced bile acid synthesis to 5% of control value; the same dose of metyrapone caused a reduction to only 85%. Inhibition of bile acid synthesis by ketoconazole was followed by a marked overshoot. At 28 hr after injection of 50 mg/kg of the drug, formation of bile acids was stimulated maximally by 45% compared to control value and remained elevated for more than 20 hr thereafter. Synthesis of all primary bile acids was affected to the same extent. Cholesterol 7 alpha-hydroxylase activity in livers of ketoconazole treated (30 mg/kg) rats with an intact enterohepatic circulation was increased by 70% at 16 hr after i.p. injection of the drug. During the very large decrease of biliary bile acid output with ketoconazole, bile flow rate was relatively increased, due to stimulation of the bile acid-independent fraction of bile flow. The latter effect can probably be explained as caused by biliary secretion of osmotically active metabolites of ketoconazole. PMID- 2586234 TI - Rhizomucor miehei triglyceride lipase is processed and secreted from transformed Aspergillus oryzae. AB - The cDNA encoding the precursor of the Rhizomucor miehei triglyceride lipase was inserted in an Aspergillus oryzae expression vector. In this vector the expression of the lipase cDNA is under control of the Aspergillus oryzae alpha amylase gene promoter and the Aspergillus niger glucoamylase gene terminator. The recombinant plasmid was introduced into Aspergillus oryzae, and transformed colonies were selected and screened for lipase expression. Lipase-positive transformants were grown in a small fermentor, and recombinant triglyceride lipase was purified from the culture broth. The purified enzymatically active recombinant lipase (rRML) secreted from A. oryzae was shown to have the same characteristics with respect to mobility on reducing SDS-gels and amino acid composition as the native enzyme. N-terminal amino acid sequencing indicated that approximately 70% of the secreted rRML had the same N-terminal sequence as the native Rhizomucor miehei enzyme, whereas 30% of the secreted rRML was one amino acid residue shorter in the N-terminal. The recombinant lipase precursor, which has a 70 amino acid propeptide, is thus processed in and secreted from Aspergillus oryzae. We have hereby demonstrated the utility of this organism as a host for the production of recombinant triglyceride lipases. PMID- 2586235 TI - Synthesis of trideuterated O-alkyl platelet activating factor and lyso derivatives. AB - Racemic heavy isotope analogs of 1-O-alkyl-sn-glycero-3-phosphocholine (lysoPAF) and 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (PAF) were prepared for use as internal standards to facilitate quantitative studies based on mass spectrometry. Starting from pentadecane-1,15-diol and rac-glycerol-1,2-acetonide, a convergent synthesis of 1-O-[16'-2H3]hexadecyl and 1-O-[18'-2H3]octadecyl rac glycero-3-phosphocholine and their acetyl derivatives is described. Three deuterium atoms were introduced at the terminal position of the 1-O-alkyl group by displacement of the p-toluensulfonyl group from 1-O-alkyl-15'-p toluensulfonate and 1-O-alkyl-17'-p-toluensulfonate with [2H3]-methylmagnesium iodide. The 1-O-alkyl-17'-p-toluensulfonate was obtained by reaction of the 1-O alkyl-15'-p-toluensulfonate with allylmagnesium bromide, followed by reductive ozonolysis and treatment with p-toluene-sulfonyl chloride. The hydroxyl group at C-2 was protected by a benzyl group and removed at a late stage in the synthesis. This provided the corresponding lyso-derivatives or allowed preparation of racemic PAF by subsequent acetylation of the free hydroxy group. The phosphocholine moiety was introduced at glycerol C-3 by reaction with bromoethyldichlorophosphate and trimethylamine. The synthetic compounds were analyzed by FAB/MS and GC/NICIMS. They were shown to contain less than 0.6% protium impurity. PMID- 2586233 TI - Phospholipid content and fatty acid composition of human heart. AB - Phospholipid content and fatty acid composition of human heart were determined on 36 biopsy specimens collected during open heart surgery. The main phospholipid classes, phosphatidylcholine (PC), phosphatidylethanolamine (PE), diphosphatidylglycerol (DPG), and sphingomyelin (SPH) were separated by HPLC, quantified, and converted to fatty acid methyl esters which were chromatographed on capillary GLC columns. Sex and age (mainly 40-70) of patients had no significant influence on the relative distribution of phospholipid classes and only a slight effect on fatty acid composition. Incorporation of trans 18:1 in phospholipid classes was low. cis and trans octadecenoic isomers seemed to be selectively incorporated, the delta 9 and delta 11 cis or trans isomers being predominant. Human and rat data were compared, and some species differences were noticed. In human PC, palmitic acid is higher and stearic acid much lower than in rat PC. Saturated dimethyl acetals (16:0 and 18:0) in PC and PE were greater for humans. Incorporation of 20:4 n-6 in human PE is higher than in rat PE. PMID- 2586236 TI - Serum fatty acid profiles after intravenous medium chain triglyceride administration. AB - The serum fatty acid profiles of patients receiving either intravenous medium or long chain triglycerides were studied. Seventeen hospitalized patients, dependent on total parenteral nutrition, were randomly enrolled into a prospective study. The total parenteral nutrition (TPN) delivered amino acids and glucose and either a 75% medium chain triglyceride and 25% long chain triglyceride (MCT group) physical mixture or all long chain triglyceride (LCT group), as the respective fat sources. The amino acids and glucose were given continuously, and the lipid was given for 10 hours each day over five days. Fatty acid profiles on serum triglycerides and free fatty acids were done in the morning before any lipid was given and also later in the afternoon, near the end of the lipid administration, on days 1, 3 and 5. Medium chain fatty acids rose quickly in the triglyceride fraction in patients given MCT. Rapid MCT hydrolysis occurred as evidenced by the appearance of medium chain fatty acids in the free fatty acid fraction in the afternoon sampling. Clearance of the hydrolyzed medium chain free fatty acids (MCFFA) occurred so that little, if any, were present in the morning sampling one day later. Long chain fatty acids, as either triglycerides or free fatty acids, showed expected increases during the daily infusion, but not of such relative magnitude as the medium chain fatty acids. Medium chain fatty acid incorporation into the phospholipid or cholesterol ester fractions by the end of the five-day feeding period was present but minimal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2586237 TI - Plasma lipoproteins in dairy cows with naturally occurring severe fatty liver: evidence of alteration in the distribution of apo A-I-containing lipoproteins. AB - The relationships between fatty liver in dairy cows and reduced levels of plasma lipoproteins, and particularly of low density lipoproteins (LDL), has been previously described. Since electrophoretic heterogeneity of ultracentrifugally isolated LDL (d, 1.006-1.063 g/ml) has been found, the exact nature of this reduction in cows with fatty liver was investigated. Lipoproteins from control and severely afflicted animals were isolated by ultracentrifugation and affinity chromatography on heparin-Sepharose CL 6 B. Gradient gel electrophoresis of lipoproteins on 4-30% gels and an immunolocalization study of apoprotein A-I (apo A-I) showed that control animals have two subpopulations of apo A-I-containing particles with a mean radius of 6.52 and 5.05 nm. In the fatty liver cows, the former was clearly shifted toward smaller particles. We concluded that the depressed level and compositional modifications of LDL in severe fatty liver cows result from a decrease in the oversized apo A-I-containing lipoproteins which can be isolated in the LDL density range. This could stem from the decreased supply of triglyceride-rich lipoprotein surface components for the production of these lipoproteins. The modifications can be plausibly explained by a reduced synthesis or secretion of very low density lipoproteins (VLDL) by the liver. PMID- 2586238 TI - Platelet-activating factor regulates phospholipid metabolism in human neutrophils. AB - This study extended the earlier finding that platelet-activating factor (1-O alkyl-2-acetyl-sn-glycero-3-phosphocholine) promotes arachidonic acid incorporation into neutrophil phosphatidylinositol (PI) and phosphatidylcholine (PC). In the present study the effect of PAF on fatty acid uptake by human neutrophils and the incorporation of extracellular linoleic acid and palmitic acid into phospholipids were investigated. Incubation of 10(-7) M PAF with neutrophils and radiolabeled arachidonic acid or linoleic acid or palmitic acid for 1-10 min resulted in an increased rate of loss of label from the incubation medium. PAF stimulated the incorporation of linoleic acid and palmitic acid most significantly into PI and PC. The magnitude of stimulation was greater in PI than in PC for the incorporation of linoleic acid, and vice versa for the incorporation of palmitic acid. The positional distribution of linoleic acid and palmitic acid in PI and PC and the mass of these phospholipids were not altered in PAF-stimulated neutrophils. An increased incorporation of all three fatty acids into both diacyl and alkylacyl species of PC was demonstrated after a two minute incubation of cells with PAF. While more radioactivity was recovered in the diacyl species, the magnitude of increase of radioactivity in the alkylacyl species was more pronounced than that in the diacyl species of PC. These results suggest that both increased fatty acid uptake and increased available lysophospholipids may be contributory to the increased phospholipid acylation induced by PAF. PMID- 2586239 TI - Temperature lability and cAMP-dependent protein kinase activation of cholesteryl ester hydrolase as a function of age in developing rat testis. AB - Cholesteryl ester hydrolase (CEH) was measured at 32 degrees C and 37 degrees C, and with and without cofactors for stimulation of cyclic AMP-dependent protein kinase, in 104,000 X g supernatants from rats aged 14-365 days. Activity at the two temperatures was also partially resolved by cation exchange FPLC. Total specific activity of CEH was relatively constant, with or without addition of cofactors, from 14 to 47 days, during which time temperature labile CEH was a very small fraction of total CEH activity. At later times, 51-150 days, activity was increased as much as two-fold, both with and without cofactors, with most of the increase occurring in the temperature labile fraction. Activation of temperature stable and temperature labile activities, where present, by protein kinase cofactors could be demonstrated in all age groups, but was highly variable as a function of age and protein concentration used in the assay. Apparent induction of temperature labile activity over the interval 47-51 days coincides with reported increases in testosterone synthesis and first appearance of spermatozoa in the testis. This and other lines of evidence suggest unique roles for these enzymes in regulation of availability of free cholesterol for testosterone and membrane synthesis, respectively. PMID- 2586240 TI - Diffuse nodular regenerative hyperplasia of the liver (DNRH). A clinicopathologic study of 24 cases. AB - The authors report 24 cases of diffuse nodular regenerative hyperplasia of the liver (DNRH) seen in a General Hospital during the last 9 years (prevalence: 3'1/100,000, incidence: 0'34/100,000). DNRH was diagnosed in 0.52% of the liver biopsies and 0.72 of the autopsies. These results suggest that DNHR is probably more frequent than suspected, and 1 DNRH was seen for each 39 biopsied cases of liver cirrhosis. Fourteen patients did not have hepatic symptoms. Portal hypertension was present in 9 cases. The biochemical disturbance most frequently found was a moderate elevation of GGT and APh, associated with slight elevation of SGOT, SGPT and bilirubin levels. Normal liver function tests could be seen (3 cases). Previous exposure to potentially hepatotoxic drugs or chemicals was discovered in 15 cases (62.5%). Diseases associated were circulatory disturbances (6 cases), autoimmune disease (5 cases), hemopathies (5 cases), and visceral carcinomas (4 cases). Two patients were recipients of renal transplant. Nodules distributed through the whole liver tissue were found in 16 cases, while 8 patients showed areas of normal parenchyma in their livers. Impairment of small hepatic vessels was detected in 16 cases. Some uneven cytologic findings were discovered: clusters of small basophilic cells (4 cases), large clear cells (8 cases), and dysplastic hepatocytes (10 cases), which suggests that DNRH could be a preneoplastic condition. PMID- 2586241 TI - Perisinusoidal cells (Ito-cells) enlargement in a family with myotonic dystrophy. AB - Two cases are reported, a daughter and her mother who both have myotonic dystrophy with abnormalities of liver function tests and an important perisinusoidal cell enlargement without other pathologic features. In both cases, the myotonic dystrophy was clinically obvious and confirmed by electromyography. No other causes of perisinusoidal cell enlargement were found including vitamin A intake, psoriasis, viral disease or alcoholism. These observations suggest a genetic linkage and that serum test abnormalities could be associated with a perisinusoidal cell change. PMID- 2586242 TI - Depressed monocyte production of interleukin-1 and tumor necrosis factor-alpha in patients with alcoholic liver cirrhosis. AB - Interleukin-1 and tumor necrosis factor-alpha activity by E. coli lipopolysaccharide-triggered monocytes were studied in patients with chronic alcoholic liver disease. Monocytes from cirrhotic patients were shown to have a significant reduction in IL-1 and TNF-a activity, compared with that from age- and sex-matched healthy controls. These findings indicate further immunoregulatory disturbances concerning alcoholic liver cirrhosis. PMID- 2586243 TI - Maryland and international health. PMID- 2586244 TI - Malaria in Maryland since 1960: incidence and research. PMID- 2586245 TI - Statistics and soap operas: population dynamics at Hopkins. AB - Since its inception in 1964, the Department of Population Dynamics has broken new ground in building interdisciplinary collaboration among the diverse fields of biological, social, and management sciences. The collaboration has produced uniquely well-prepared professionals, yielded some innovative research efforts, and advanced training and communication in the field of family planning. From Dr. Paul Harper's determination to build a center for sharing experiences in population planning, a world center for population dynamics has grown. PMID- 2586246 TI - Battling blindness throughout the world: a team of scientists in Maryland leads the way. PMID- 2586247 TI - Reverse foreign aid: the foreign medical graduate. PMID- 2586249 TI - Health care of merchant seamen. PMID- 2586250 TI - Maryland's travelers' clinics. PMID- 2586248 TI - Geographic epidemiology. PMID- 2586251 TI - American practitioners and the global primary care movement. AB - In conclusion, comparative studies of primary health care in various parts of the world can lead to new solutions for underserved communities in Maryland and other parts of the US. Careful review of how similar principles work under different circumstances will open new approaches. Current international experience shows that each country must evolve its own health care system. We have much to learn from those who are poorer than we, where limited resources stimulate local innovation and less waste. PMID- 2586252 TI - Demographic and epidemiological perspective on genetic disorders. PMID- 2586253 TI - Gaps in service: patient/family perspective. PMID- 2586254 TI - Prenatal genetic concerns. PMID- 2586255 TI - Assessment of genetic disorders: pediatrics. PMID- 2586256 TI - Immunotherapy of disseminated renal cell carcinoma. PMID- 2586257 TI - [Determination of the functioning volume of the liver by multipositional scintigraphy and emission-computed tomography]. AB - The paper is concerned with methods for the determination of the liver volume using polypositional scintigraphy (PS) and computed emission tomography (SPECT). The accuracy of both methods was assessed using a liver phantom. The methods were tested in clinical practice on patients with diffuse liver lesions. A liver volume value compared with values in normometric tables as well as differences between a geometrical volume calculated by PS and a volume calculated by SPECT were of diagnostic importance. PMID- 2586258 TI - [The concentration of carcinoembryonic antigen and carbohydrate antigen Ca-19-9 in the blood serum in cancerous diseases of the gastrointestinal tract]. AB - The results of comparative investigation of 266 cancer patients, 44 patients with benign G. I. tract diseases and 66 healthy subjects using 2 tumor markers (CEA and Ca-19-9) showed the diagnostic value of both methods, not exceeding 38-42%. The most informative were the data on patients with pancreatic and colorectal cancers as well as in patients with detected metastases. Significant differences in the sensitivity, specificity and diagnostic informative value between the two markers were undetectable. PMID- 2586259 TI - [The developmental aspects of nuclear medicine in the USSR]. PMID- 2586260 TI - [An algorithm for processing the data from the radionuclide angiography of the internal organs]. AB - The paper is devoted to the theoretical substantiation and approaches to the determination of the main parameters of circulation of the internal organs on the basis of the results of indirect radionuclide angiography. Formulas for the calculation of circulation mean time, blood flow volumetric rate and its fraction of the cardiac output were given. Using algorithms, cited in the paper, one could prepare programs for the processing of radionuclide angiography data on computers. PMID- 2586261 TI - [Assessment of the effective ejection fraction for the right and left ventricles based on radionuclide ventriculographic data]. AB - The authors proposed a method of the evaluation of the effective right and left ventricular ejection fraction on the basis of radionuclide ventriculography data. They substantiated theoretically this approach and gave formulas for ejection fraction calculation. Shortcomings of dynamic and static radioventriculography were discussed. This method could be used in clinical practice. PMID- 2586262 TI - [Guarantees of the quality of the training of specialists in nuclear medicine]. AB - The absence of a social order for specialists in nuclear medicine hampers the process of making curricula and programs directed to achieving professional skills. The category of a specialist in nuclear medicine was not envisaged in the system of medical education and in the Nomenclature of physician's posts. It is proposed that a specialist in nuclear medicine should be introduced in the Nomenclature. The system of control of knowledge and skills should be worked out on a uniform basis in order to become a guarantee of the training of such specialists and raising their professional skills. PMID- 2586263 TI - [A comparative evaluation of methods for determining the glomerular filtration rate by 169Yb-DTPA clearance]. AB - The authors present the results of comparative analysis of 7 radionuclide clearance methods for the determination of glomerular filtration rate (GFR), based on single administration of 169Yb-DTPC. A reference method was based on the determination of GFR by a curve of a decrease in plasma concentrations with subsequent biexponential analysis on a DVK-2M computer. Methods of the determination of GFR based on 2 blood drawing tests after achieving a uniform distribution of the indicator in its volume of dilution (1) and extracorporal labeling of gamma radiation by a precordial detector (2) showed the highest degree of correlation with the reference method (r = 0.918, p less than 0.001 and r = 0.920, p less than 0.001, respectively). The use of both methods based on a single-chamber model of renal clearance, led to good results, provided the measurements were to start not earlier than 1.5 h after administration of the indicator. PMID- 2586264 TI - [Quality control in emission-computed tomography]. AB - The authors considered the major aspects of the control of the quality of computed emission tomography (SPECT), assessed the influence of the physicotechnical parameters of the instrument, parameters of recording of results and methods of their processing on end-results of investigations. The authors propose a list of controlled parameters, methods of testing and their periodicity; they also describe the techniques and results of some phantom studies using SPECT with the Jaszczak phantom. PMID- 2586265 TI - [The radiation therapy of experimental brain tumors by using the radiosensitizing preparation xanthobin (8-bromocaffeine)]. PMID- 2586266 TI - Toxicological blunders. PMID- 2586267 TI - Fires. PMID- 2586268 TI - The Bradford Fire Disaster. Part 1. The initial investigations: who died, where and how? AB - In May 1985 a football ground fire resulted in 50 deaths. All the bodies were severely burned. This paper provides an account of the planning and methods used in the initial investigation and assesses their value and the problems encountered. PMID- 2586269 TI - The Bradford Fire Disaster. Part 2. Accident reconstruction: who died, when and why. AB - The circumstances of the Bradford Football Stadium Fire have been described in Part 1. Part 2 relates the positions in which the bodies were found, their carbon monoxide concentrations, and the physical configuration of the stand to the seat of the fire. It also examines the causes of the high death toll and makes recommendations for the future planning and management of sports stadiums. PMID- 2586270 TI - Immediate causes of death in fires. PMID- 2586271 TI - Forensic evidence for the defence. PMID- 2586272 TI - Local dental anaesthesia and evidential breath testing: the effect of injection of local anaesthetic on lip seal. AB - The effect of local anaesthetic infiltration on the ability of subjects to provide adequate specimens of breath for analysis using an evidential breath testing device was assessed. The results showed that in ten out of the fourteen cases there was no impairment of the ability to provide the specimens of breath at any time. Within two hours of the administration of a local anaesthetic all subjects were able to provide the requisite samples. PMID- 2586273 TI - Treatment for offender patients: how should success be measured? AB - The criteria used to judge the success of treatment for mentally ill (psychotic) patients are the same for offenders and non-offenders. For those offender patients detained as psychopaths, the incremental validity of the medical concept is dubious and recourse is often made to the use of the criminal criterion of reconviction in order to measure therapeutic effectiveness. One such study is reported here and others are reviewed. It is argued that reconviction is not a valid measure of psychiatric treatment and that the criteria used to judge therapeutic effectiveness in forensic psychiatry should not differ from those used in all other forms of psychiatric care. PMID- 2586274 TI - A case of fatal suffocation during an attempt to swallow a pool ball. AB - An unusual case of accidental death from suffocation during an attempt to 'swallow' a pool cue ball is presented. PMID- 2586275 TI - Pseudologia Fantastica: a case study of a man charged with murder. AB - A case of Pseudologia Fantastica is presented in a man charged with murder. Psychological assessment revealed him to be highly compliant and suggestible, consistent with early research (Healy and Healy, 1915) which showed pathological liars to be suggestible to misleading information. A specific dyslexic disorder is also demonstrated, and the possible mechanisms behind the man's lying considered. Some implications regarding the reliability of the man's varying confessions to the police are discussed, and parallels are drawn between this case and that of Timothy Evans, who in 1950 was hanged for murder. PMID- 2586276 TI - Referrals to a new regional secure unit--what happens to patients refused admission? AB - The new Regional Secure Unit for the West Midlands, the Reaside Clinic, had a total of 85 patients referred for admission during the first year of operation, of whom 32 were considered unsuitable for admission. The characteristics and outcome of these patients are discussed, together with the implications for forensic psychiatrists, general psychiatrists and prison medical officers. PMID- 2586277 TI - Injury Severity Score (ISS) as a yardstick in assessing the severity and mortality of various abdomino-pelvic trauma hospitalized victims--a clinical vis a-vis autopsy study. AB - A summary of 51 cases of vehicular accident showing abdomino-pelvic trauma, along with associated other regional injuries, were studied at the Department of Forensic Medicine at MAM College and Associated Hospitals in New Delhi during 1986. A detailed Injury Severity Score (ISS) was done in all the cases and the relationship of ISS during their clinical treatment phase and after death was studied, keeping in mind factors such as age, survival periods, etc. PMID- 2586278 TI - 6-phosphogluconate dehydrogenase typing from dried bloodstains--under Indian conditions. AB - As yet, there is no report available on the stability studies of 6 phosphogluconate dehydrogenase enzyme in India. 469 bloodstains prepared in the laboratory using a variety of substrates commonly encountered in case examination have been analysed by starch gel electrophoresis. The utility of this parameter under various climatic conditions prevalent in India has also been evaluated. Except in the cases of relatively fresh samples of blood, the PGD isoenzyme system seems not to be very suitable in Indian conditions. PMID- 2586279 TI - Fatal suicidal hangings among prisoners in jail. AB - A study of suicidal death by hanging, which occurred when the victim was in jail, was performed on the case files of the Metropolitan Dade County Medical Examiner Department in Miami, Florida, for the ten-year period July 1978 to July 1988. A total of 23 fatalities occurred. These were categorized epidemiologically. A discussion ensues concerning what can be done to prevent such tragedies. PMID- 2586280 TI - Detecting and proving the sexual abuse of children. PMID- 2586281 TI - Serum strontium estimation as a drowning indicator: statistical evidence revised. PMID- 2586282 TI - [Work organization for the healthy child room]. PMID- 2586284 TI - [Systemic scleroderma and the physical methods for its treatment]. PMID- 2586283 TI - [The organization of health improvement for the workers of industrial enterprises]. PMID- 2586285 TI - [Physiotherapy in acute hematogenous osteomyelitis in newborn and nursing infants]. PMID- 2586286 TI - [The physical therapy of exogenous-constitutional obesity]. PMID- 2586287 TI - [The problems of ecology are the problems of all mankind]. PMID- 2586289 TI - [Candidiasis of the oral cavity]. PMID- 2586288 TI - [Vitamin therapy in the combined treatment of periodontal diseases]. PMID- 2586290 TI - [Radiation therapy and the related deontological aspects of the nurse's work]. PMID- 2586291 TI - [Facial neuritis]. PMID- 2586292 TI - [Hygromas in children]. PMID- 2586293 TI - [Industrial hygiene in work with high-frequency ultrasonic devices]. PMID- 2586294 TI - [The Bulgarian journal Meditsinski rabotnik in 1987]. PMID- 2586295 TI - Twelve tips for designing instructional text using desktop publishing. PMID- 2586296 TI - What is ... normative versus criterion-referenced assessment. AB - Any reform of the current medical curriculum requires a reappraisal of the principles and practices of the evaluation system. The norm-referenced test which at this time is the primary method of evaluation was initially designed to rank order students for the purpose of selection. Difficulties arise when it is used, as it currently is for the assessment of competence. The norm-referenced test is often insensitive to instruction and, while it provides information regarding the relative strengths and weaknesses of students in comparison to their peers, it does not provide an estimate of the absolute level of performance achieved. In addition to promoting competition among students, the norm-referenced test is less suitable for programme evaluation. As it is the principal responsibility of a medical school to produce competent physicians and not to rank order them, it is more reasonable to compare student achievement to an external standard of performance or criterion. Criterion-referenced testing, then, is more suitable for the assessment of competence and, within this setting, percentage competency scores can be utilised when there is a need for the rank ordering of student achievement for the purposes of selection. It is recommended that criterion referenced testing be the primary method of evaluation, as it best meets the objectives of the medical school by emphasising the achievement of clearly established external standards and, thereby, ensuring a high quality of performance. PMID- 2586297 TI - Self-assessment in problem-based groups. AB - Medical students in a tutorial program rated themselves in Year 1 and again in Year 2 on Knowledge, Reasoning, Communication and Interpersonal Skills. Student and tutor ratings were similar in Year 1 but different in Year 2. Both self- and tutor ratings increased from Year 1 to Year 2 but self-ratings were independent of achievement while tutor ratings were related to achievement. Possible reasons for these results were discussed with reference to the learning goals of the tutorials. PMID- 2586298 TI - Responding to perceived needs of the twenty-first century: a case study in curriculum design. AB - Mercer University School of Medicine was established in response to the shortage of primary care physicians in medically underserved Georgia. Originally patterned after the McMaster model of medical education, Mercer found it necessary to modify the three academic programs of the first 2 years of a 4-year undergraduate medical education curriculum. Since accepting students in 1982, though, it has retained many of the essential qualities of problem-based learning and those educational experiences that prepare community responsive physicians to practice in medically underserved areas. PMID- 2586299 TI - A problem-based clinical course in general internal medicine. AB - General internal medicine instruction in an unsuccessful lecture-based course was replaced by a clinical problem-based 'junior clerkship'. Hospital and ambulatory clinic instruction was centered around major common medical problems. Tutors willingly adopted a problem-based teaching approach and participated eagerly in a multi-component evaluation. Students and instructors responded favourably to questionnaires regarding the use of a problem list, the content and face validity of the course and the usefulness of the evaluations as learning experiences. PMID- 2586300 TI - Medical ethics education in the eighties: a study of five medical schools. AB - Five Southern California medical schools were examined using a case study approach. In-depth interviews were conducted with faculty members and administrators from Loma Linda University, the University of Southern California, and the University of California at Irvine, Los Angeles, and San Diego, Schools of Medicine. Using an interview instrument based on a needs assessment model, the interviewer examined interviewees' perspectives on the current curriculum and their opinions on the 'ideal' medical ethics curriculum. Key issues of concern for each medical school's medical ethics curricula were discussed. PMID- 2586301 TI - Nursing students in transition--from hospital to college and back again. AB - Nursing education is increasingly moving from hospital-based schools to institutions for tertiary education. The change in style and content of nursing courses has created difficulties for many students and their teachers. Many nursing students find the transition to tertiary study confusing and in the early stages of their course find study skills assistance valuable in adapting to new ways of writing and learning. Student difficulties usually manifest themselves in assignment writing and are often interpreted by academic staff and students as poor English expression. Most nursing students assisted by the study skills tutor at the South Australian College of Advanced Education in 1986-87, however, had problems with their writing for more fundamental reasons: (i) courses conflicted with students' earlier learning experiences; (ii) the conventions of academic argument were unknown; (iii) vocabulary and linguistic structures were inappropriate for new demands. These problems are discussed and some support strategies described. PMID- 2586302 TI - The effectiveness of microtraining in developing pharmacists' communication skills: a study of personality and attitudes. AB - This paper examines the effectiveness of a microtraining programme in developing the communication skills of pharmacists. In particular, it investigates the influence of this programme upon self-reported communication activities in the actual work environment. Inter-relationships are also obtained between the personality of participants, their attitude to the microtraining technique and the degree of self-reported influence on work performance. Overall, participants demonstrated a strongly positive attitude to, and indicated that they had been highly influenced by, the microtraining programme. It was also found that there was a significant and positive correlation between extroversion and attitude to microtraining (p less than 0.005). Furthermore, a positive correlation was also obtained between attitude and influence although this did not reach the 0.5 level of significance. It is concluded that microtraining is a promising technique for developing the communicative competence of pharmacists, but may need to be modified to cater for personality differences within trainees. PMID- 2586303 TI - Administrative skills for academic physicians. AB - To function effectively within the multifaceted environment of the academic medical center, academic physicians need to heighten their understanding of the economics of the health care system, and further develop their leadership and managerial skills. A literature base on organizational development and management education now exists that addresses the unique nature of the professional organization, including academic medical centers. This article describes an administration development curriculum for academic physicians. Competency statements, instructional strategies and references provide the academic physician with guidelines for expanding their professional expertise to include organizational and management skills. The continuing success of the academic medical center as a responsive health care system may depend upon the degree to which academic physicians gain sophistication in self-management and organizational administration. PMID- 2586305 TI - The first private medical faculty in the Federal Republic of Germany: University of Witten/Herdecke. PMID- 2586304 TI - The integration of computer conferencing into the medical school curriculum. AB - A computer conference was developed for use with students, faculty, and staff at a large state-funded medical school. The conference was intended to increase communication among these groups which study, work, and train at a variety of locations across the state. To date, 583 participants (91% are students, 6% are faculty, and 2% are staff) have discussed a variety of academic, ethical, social, and administrative issues. Conference use is required during the obstetrics gynecology third year clerkship, and has also been used to evaluate courses and critique course examinations. The procedures for creating a computer conference, implementing its use in the curriculum, and evaluating its effectiveness are discussed. PMID- 2586307 TI - As it happens: conversations overheard in the medical school. PMID- 2586306 TI - An introduction to the consultation: a brief teaching method and its evaluation. PMID- 2586308 TI - Private psychiatric hospitals, United States: 1983-84 and 1986. AB - In 1986, a total of 314 private psychiatric hospitals provided inpatient services in 47 States and the District of Columbia (D.C.); 114, outpatient care services in 35 States and D.C.; and 102, partial care services in 26 States and D.C. Between 1983 and 1986, the total number of inpatient, outpatient, and partial care episodes in these hospitals increased from 333,731 to 483,284. During the 1983-86 period, the number of private psychiatric hospitals increased from 220 to 314. Almost all of this increase occurred among hospitals operating on a for profit basis. By 1986, these hospitals represented three-quarters of all private psychiatric hospitals. With the exception of small not-for-profit hospitals, all bed-size groups in private psychiatric hospitals increased between 1983 and 1986. The number of beds in private psychiatric hospitals increased 41 percent, from 21,474 in 1983 to 30,201 in 1986. Similarly, the number of inpatient additions increased from 164,732 to 234,663 in this period, and inpatients at end of year increased from 16,079 to 24,591. The number of outpatient additions increased by more than half, from 77,589 in 1983 to 123,355 in 1986, and the outpatients at the end of the year rose from 79,598 to 135,606 (70 percent). In the same period, the number of partial care additions increased from 5,642 to 8,820, and partial care patients at the end of the year rose from 3,218 to 3,856 (20 percent). In the 1986 year-end inpatient caseload, males slightly outnumbered females, and the patient population was predominantly white, non-Hispanic. About two-fifths of the patients were under age 18, slightly over half were age 18-64 years, and 8 percent were age 65 or older. Mental illness was the major disability, with alcohol and drug abuse a distant second. By comparison, a smaller proportion of patients were under age 18 in 1983 (31 percent), and a larger proportion were age 18-64 (61 percent). In outpatient and partial care services, a more even distribution of the sexes was generally observed. Proportionately fewer outpatients were under age 18, more were between 18 and 64, and fewer were diagnosed with alcohol and drug abuse, compared with inpatient services. Also, proportionately more outpatients were Hispanic. Concomitant increases occurred in the number of full-time equivalent (FTE) staff, as well as in the amount of money expended by private psychiatric hospitals. FTE staff increased from 42,202 in June 1984 to 58,912 in November 1986.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2586309 TI - The Secretary's Work Group on Pediatric HIV Infection and Disease. PMID- 2586310 TI - Background, epidemiology, and impact of HIV infection in children. AB - There was substantial difficulty in the early years of the HIV epidemic in confirming the presence of this infection in children. Serological testing finally allowed the identification of a spectrum of clinical expressions. An understanding gradually developed about the serious central nervous system involvement in children, which is more direct and intense than that usually seen in adults. My early personal experiences in this work were described. PMID- 2586311 TI - The impact of HIV infection on the hemophilia community. AB - The hemophilia community has been rocked by the catastrophe of AIDS. The use of blood products that had first restored the potential for normal survival turned out also to bring involvement with, or the threat of, HIV infection. Persons with hemophilia are now burdened with fear and discrimination. Strong leadership has come from the National Hemophilia Foundation in the provision of needed support and understanding. PMID- 2586312 TI - HIV infection and developmental services for adults. AB - The achievement of community living and greater personal independence has placed adults with developmental disabilities in a potentially vulnerable position regarding acquisition of HIV infection. Early surveys have identified a limited number of individuals who have become infected. Few states have undertaken planning for assurance of appropriate services. Program managers must consider the diverse educational and ethical issues involved; advisory committees can be of assistance. Strong antidiscrimination measures will be required for the protection of adults with developmental disabilities and HIV infection. PMID- 2586313 TI - Developing an AIDS prevention education program for persons with developmental disabilities. AB - The AIDS epidemic poses a serious threat to people with developmental disabilities, the magnitude of which has not yet been fully realized by many professionals working with this population. Models for effective AIDS prevention education have been developed, however, within other populations. Key principles utilized in existing models were discussed and recommendations presented on how to adapt these models when designing programs for people who have developmental disabilities, most specifically, those in the mild/moderate range of mental retardation. PMID- 2586314 TI - The segregation of an adolescent in foster care who is HIV seropositive and developmentally disabled. AB - Segregation, based on fear of liability, is being practiced regarding persons with HIV infection. The story is told of 16-year-old Chris, who has mental retardation and a positive blood test for HIV infection. He lost his foster care placement, underwent a lengthy hospital admission, and had a long and complicated process for resolution of his program plans. Also involved were breach of consent, violation of confidentiality, and discrimination. Policy concerns about decision-making in the child welfare system regarding persons with HIV infection were discussed. PMID- 2586315 TI - Public opinion, public policy, and HIV infection. AB - An analysis of the interplay between public opinion and public policy in terms of HIV infection yielded a four-stage framework for considering the development of public policy in relation to a highly charged issue. The phases are denial, irrationality, acceptance, and the development of a rational response. As we move into Phase 4 in relation to HIV infection, we should take a lesson from the history of the development of public policy for persons with disabilities and promote strong federal leadership and a federal antidiscrimination policy that includes persons with HIV infection as a part of the group of persons with disabilities. PMID- 2586316 TI - Judicial attitude toward legal rights and AIDS. AB - Modern judicial activism--establishing caselaw that functions as law until statutes are subsequently enacted--has been the hallmark of the variety of legal issues surrounding the HIV condition and AIDS diseases. Most federal and state courts have been compelled to resolve many HIV/AIDS-related controversies in advance of legislative guidance and have generally done so by protecting the civil rights of persons with HIV/AIDS under established law as well as the traditions of Western law. PMID- 2586318 TI - Diagnostic dissonance. PMID- 2586317 TI - Protection of persons with HIV infection: concluding remarks. PMID- 2586319 TI - Presidential address 1989. AAMR. PMID- 2586320 TI - Indicators of impact of services on persons with developmental disabilities: issues concerning data-collection mandates in P.L. 100-146. AB - Public Law 100-146 requires the Administration on Developmental Disabilities to report to the Congress in 1990 on the status of services to persons with developmental disabilities. Considerable effort has been devoted by the National Association of Developmental Disabilities Councils to providing a national methodology for characterizing state services and for surveying consumer satisfaction with these services; but these data alone will not be sufficient to adequately characterize all variables required by the 1990 report. Definitional, conceptual, and methodological issues related to measurement of scope and extent of services, documenting eligibility and accessibility, and estimating the effectiveness of services was reviewed. A framework was suggested for integrating data-collection with consumer satisfaction survey efforts already underway. PMID- 2586321 TI - Twenty-year tuberculin testing in an institution for persons with mental retardation. AB - Tuberculin Purified Protein Derivative skin test conversions and reversions were followed over 20 years in 363 patients in an institution for persons with mental retardation. Of these, 88.7% remained negative and 5.2% remained positive. Changes included 2.7% reverting to negative, 0.3% converting to positive, and 3.1% showing two to five negative-positive changes, with varying degrees of positivity over the years. Some patients showed only transient positive reactions. Most changes could not be explained by clinical evidence of infection, but multiple causes were felt to be likely. The discovery of converters was minimal, and the usefulness of routine skin testing in such institutions is doubtful. PMID- 2586322 TI - Coping responses of adolescents with and without mild learning handicaps. AB - Five sentence completion stems about coping were administered to 60 adolescents (30 learning handicapped [mean IQ = 76], 30 nonhandicapped). Content analysis revealed that sources of everyday stress fell into four categories that reflected developmental concerns: frustrated efforts, direct conflict, social injustice, and performance issues. Coping responses were initially coded as active or passive and then further subcategorized into more specific coping behaviors. Analysis indicated that students with learning handicaps did not report any instances of performance issues as a source of stress and gave more passive coping responses than did students who were not handicapped. Sources of stress as well as coping responses revealed group differences in adolescents' perceptions of dependency and control. PMID- 2586323 TI - Providing language consultation in the natural context: a model for delivery of services. AB - The role of speech-language pathologists in providing consultation services to personnel dealing with children with severe language delays was discussed. A four phase consultation model, emphasizing the delivery of services in the natural context, was advanced and activities within each phase delineated. PMID- 2586324 TI - "Functioning" from the perspective of production supervisors. AB - Ethnographic research at two work activity centers revealed the hidden connotations of "functioning" in production supervisors' discussions of high functioning and lower functioning clients. Teachers at the centers defined functioning in narrowly academic terms, whereas supervisors used the term to connote a whole set of mental, physical, and moral traits related to job performance. Implications for communication among staff members and for treatment of clients were considered. PMID- 2586325 TI - Community-referenced activities: implications for establishing stimulus control. AB - Community-referenced activities involve skill clusters that may be extended over time and/or intertwined with collateral skills. Such multiplex response chains differ in numerous ways from the discrete responses shaped in repetitive trial instruction. Specifically, community living response chains are characterized by the length of the chain, the response classes contained in the chain, and the implicit variations within the chain. Characteristics of these activity chains were analyzed in order to exact implications for enhancing instructional procedures. Given the variety of stimulus control strategies available, this discussion may effect a more deliberate selection of a procedure that is applicable to the varied stimuli and responses in daily living activities. PMID- 2586326 TI - Breast feeding--a contraceptive? PMID- 2586327 TI - Research in an antenatal clinic--the experience of the Nottingham Mothers' Stop Smoking Project. AB - The Nottingham Mothers' Stop Smoking Project was extremely successful in helping women to stop smoking during pregnancy and in reinforcing non-smoking behaviour. This paper describes the experience of undertaking the action research project in the antenatal clinic from the points of view of the researchers, women and midwifery staff. The article outlines the practical problems encountered in attempting to adhere to a research protocol. The implementation of the project involving friendly encouragement, a carbon monoxide monitor and the offer of self help groups is described within the context of the busy antenatal clinic setting. Pregnant women's experience of the project and the views of midwifery staff are also presented. The feasibility of incorporating such projects into everyday activity is discussed. PMID- 2586328 TI - Mothers of very low birthweight babies: who supports them? AB - Delivery of a very low birthweight (VLBW) baby usually precipitates a crisis in the lives of a family, and the mother's adequacy and competence are challenged. To whom does she turn for support? Twenty-one mothers of singleton VLBW babies were interviewed on six occasions from 1 week after the birth to 3 months after the baby's discharge from hospital. At each interview they were asked whom they had found most supportive. Whilst partners were generally supportive, other relatives seemed to have difficulty knowing how to help. There was a rallying to the mother's aid during the initial crisis period after the birth and again immediately after the baby's discharge home but few sustained this effort during the chronic stages when the mother was tired, depressed and anxious. Though hospital staff were considered supportive for the most part, there were areas for improvement in their ability to listen empathically to the mother's own perceptions of events and behaviours which were at great variance to their own. Health visitors appeared to have real difficulties. They demonstrated a marked lack of knowledge and understanding and they were considered very unsupportive by many mothers. PMID- 2586330 TI - WHO issues new estimates of HIV/AIDS by the year 2000. PMID- 2586329 TI - Motivation for continuing education in midwifery. AB - Continuing education is increasingly recognised as vital for the improvement of health care. This paper discusses the findings of a study carried out to investigate whether practising midwives working in selected hospitals in Northern Ireland are motivated to participate in continuing education. A questionnaire approach was used to investigate 60 midwives of ward sister/staff midwife grades. Quantitative data were enhanced with information from semi-structured interviews. Midwives in this study conceptualised continuing education as both formal and informal learning experiences. Despite variations in the views they held of the value of continuing education to themselves, all respondents identified continuing education as being important for professional reasons. The findings suggest that midwives lack motivation to participate in informal and formal continuing education. However, the findings also indicate that encouragement and support from managers, adequate provisions of educational facilities, social responsibility and having to work night duty/part-time may influence midwives' ability to participate in available continuing education programmes. In conclusion the findings highlight the need for an effective staff appraisal system and the provision of a range of opportunities (formal and informal) for continuing education to motivate midwives to continue their education. PMID- 2586331 TI - Chlamydia trachomatis as a possible agent of human autoimmune diseases. AB - A high percentage of patients (61.2%), suspected of having rheumatoid factor and autoimmune diseases, were infected with Chlamydia trachomatis (Ct). Patients with significantly high titres (greater than 256) against Ct (53.8%), also had a significant high level of antinuclear factor and anti DNA. Complement fractions, C3, C4 and the immunoglobulins, IgG, IgA and IgM, were also found in high levels. No cases of rheumatoid factor or autoimmune disease were diagnosed in a control group of patients. The results indicate that patients infected with Ct may develop rheumatic or connective-tissue diseases. PMID- 2586332 TI - Killing rate and serum bactericidal activity of oxacillin, rifampin and ciprofloxacin against Staphylococcus aureus. AB - The bacterial activity of oxacillin, rifampin and ciprofloxacin was examined at two concentrations by the serum bactericidal rate (SBR) technique against 5 strains of methicillin-susceptible Staphylococcus aureus. The activity of oxacillin plus ciprofloxacin and oxacillin plus rifampin was also determined for 5 strains of staphylococci examining in vitro the SBR and the serum bactericidal activity (SBA). We simulated SBR and SBA in vitro using pooled human serum containing know concentrations of antimicrobial agents. The rate at which the antibiotics kill S. aureus did not rise by increasing the concentrations over the MBC. The oxacillin-ciprofloxacin combination was indifferent when tested by the rate of killing, whereas an antagonistic interaction was frequently observed with the oxacillin-rifampin combination. The SBA was determined by two methods: the technique of the Mayo Clinic that uses Mueller-Hinton broth (MHB) as the diluent and the method of Stratton in which the diluent was prepared with MHB supplemented with Ca++ and Mg++ and combined with 50% pooled human serum. The activities of oxacillin and rifampin were decreased in the presence of human serum. These results were attributed to the high protein binding of these antibiotics. Rifampin in combination with oxacillin showed antagonism against S. aureus also by the SBA method. The inhibitory activity of drugs in combination remained substantially the same as the single more active one. PMID- 2586333 TI - Antibacterial, antifungal and antitumoral activities of Micromycetes. I. Preliminary study. AB - The ability of 211 strains of Micromycetes to produce antibiotic, antifungal and antitumoral compounds has been investigated in vitro using test strains and P 388 leukemia cells. Cytotoxicity was determined on Vero cells. Convenient activities were obtained depending on the taxonomic group. Finally, 17 strains of Micromycetes were selected for their antibacterial or antifungal activities and 12 for their antitumoral properties. Investigations are in progress concerning these activities. PMID- 2586334 TI - Isolation and characterization of two rumen Streptococcus bovis bacteriophages. AB - A method for the isolation of Streptococcus bovis bacteriophages from ruminal fluid of calves is described. Thirty to 2 x 10(3) phages per ml infecting Streptococcus bovis strains 4/1 and 47/3 were isolated directly from ruminal fluid. Two bacteriophages were characterized on the basis of plaque morphology, host ranges, electron microscopic morphology and DNA restriction endonuclease digestion patterns. The F1 and F3 phages formed clear plaques of different sizes. The plaque size of the F1 phage was about 1-1.5 mm in diameter, while the plaques of the F3 phage were larger (1.5-2.5 mm in diameter). Both phages are placed in group B of Bradley's scheme and have different host ranges. The first isolation of Streptococcus bovis phage DNA is reported. Restriction analysis of their DNAs showed that phages F1 and F3 had different numbers of cleavage sites in their genomes and that they were not identical. PMID- 2586335 TI - Antigen capture ELISA for HTLV I in cell culture. AB - Recent reports have shown that HTLV I infection is widespread and that HIV/HTLV I combined infections may accelerate the progression of seropositive patients towards AIDS. In order to obtain a tool for the detection and identification of HTLV I in cell culture we have developed an antigen-capture ELISA, which is based on the use of rabbit hyperimmune serum on solid phase and mouse monoclonal antibodies against p19 and p24 as tracers. This assay has a sensitivity of 50 ng/ml, it can be used to test cell-culture fluids and does not cross-react with any other known human retroviruses. PMID- 2586336 TI - Yersinia enterocolitica 08 "American strain" isolated in Italy. AB - A strain of Yersinia enterocolitica serotype 08: b,e,f,i, "American strain", was isolated from a child suffering from febrile enteritis, without any history of foreign travel. Such a strain, very uncommon in Italy, though isolated from a sick child, lacked both in vivo and in vitro virulence-associated characteristics as lethality in mice, spontaneous autoagglutination and calcium dependency, traits correlated to a lack of the virulence plasmid. PMID- 2586338 TI - Environmental health hazards. The statistics are staggering. PMID- 2586337 TI - Blastocytosis. An epidemiological study. AB - An epidemiological survey on 33 cases of blastocytosis was conducted. This study confirms that infection is transmitted through ingestion of water, fruit or vegetables that have been contaminated by animal excrement. At our latitude blastocytosis, nourished by animal reservoirs, is widespread throughout the year without any particular seasonal incidence peak. PMID- 2586339 TI - Infectious medical waste. A Michigan perspective. PMID- 2586340 TI - Indoor air quality. There are many concerns, says MDPH. PMID- 2586341 TI - Michigan doctor encourages children to plant trees, help environment. PMID- 2586342 TI - MSMS represents members' views in amicus court cases. PMID- 2586344 TI - Physicians need to know more about environmental health risks. PMID- 2586343 TI - Michigan's triplicate prescription program now in effect. PMID- 2586345 TI - Characterization of replicative form DNA of the autonomous parvovirus mink enteritis virus. AB - Characterization of replicative form (RF) DNA of mink enteritis virus (MEV) was carried out. Most of the RF DNA were bound to terminal protein but some were free from the protein. The protein-free RF DNA increased about 7 times from 30 to 50 hr post-infection, while the DNA with protein increased less. The molecules of the replicative intermediate which were partially single-stranded DNA and bound to terminal protein were present. Two terminal conformations, "extended" and "turnaround," were observed in both ends of both terminal protein-bound and protein-free RF DNA. The 5' end labeling revealed that 5' ends of protein-free RF DNA were not blocked to phosphorylation by an amino acid or an oligopeptide which attaches to 5' ends of proteolytically deproteinized RF DNA. Restriction analysis of incomplete RF DNA which was partially double-stranded DNA showed that extended conformation was dominant in such incomplete RF molecules. PMID- 2586346 TI - A possible correlation between histological changes in regional subcutaneous tissue induced by bacterial lipopolysaccharides and their adjuvant activities. AB - Previously it was demonstrated that Klebsiella pneumoniae O3 lipopolysaccharide (KO3 LPS) exhibited much stronger adjuvant action on antibody response to subcutaneously (s.c.) injected sheep red blood cells or deaggregated bovine serum albumin than did other kinds of LPS, the R-form LPS lacking the O-specific polysaccharide chain of KO3 LPS (R-LPS), and the lipid A fractionated from KO3 LPS. We compared histological changes in the regional subcutaneous tissues of mice injected subcutaneously (s.c.) with KO3 LPS, the lipid A, and R-LPS. At the early stage after injection, KO3 LPS induced the infiltration of a large number of inflammatory cells, mainly polymorphonuclear leukocytes (PMN), at the site of injection. Neither R-LPS nor the lipid A induced the accumulation of PMN so much as KO3 LPS did. When injected s.c. with LPS from Escherichia coli O111 (EO111 LPS) and O55 (EO55 LPS), and Salmonella enteritidis (Sent LPS), the appearance of PMN at the regional site was much less than KO3 LPS. KO3 LPS could accumulate more 51Cr-labeled leukocytes at the injection site than EO111 LPS and Sent LPS. Administration of acetylsalicylic acid, which can inhibit leukocyte migration in inflammatory lesions, suppressed its adjuvant action. It was therefore suggested that the strong adjuvant action of KO3 LPS in s.c. injection might be dependent on its potent capability of accumulating PMN at the regional subcutaneous tissue. Furthermore, at the late stage after injection, the formation of several lymphoid follicles at the regional site was seen only in mice injected with KO3 LPS. It might be also related to the strong adjuvant action of KO3 LPS. PMID- 2586347 TI - [Comparative study of Candida lipolytica yeasts with various abilities to produce citrate]. AB - The growth and the activity of some enzymes were studied in a Candida lipolytica strain 12a which did not synthesize acids in a medium with glucose under the conditions of nitrogen deficiency. The substrate was not assimilated and cyanide resistant respiration did not develop in the strain under the conditions of profound nitrogen deficiency. The inability of cells to assimilate glucose at the stationary phase of growth resulted, apparently, from an abrupt decrease of phosphofructokinase and pyruvate dehydrogenase activities in the cells. The activities of pyruvate carboxylase and citrate synthase fell down abruptly at the same time. PMID- 2586349 TI - Self-organisation and living systems: Is DNA an 'artificial intelligence'? AB - There seems little doubt that the maintenance and development of living systems is crucially dependent on an internal organisation of monumental complexity- particularly in higher living species. It is suggested that current thinking- particularly relating to the role of DNA in the total process cannot explain the underlying mechanisms and that a radical rethinking will be necessary. To this end it is proposed that DNA has a unique molecular electronic structure enabling it to operate as a computer analogue system for the highly efficient storage of information and as a type of artificial intelligence through which the information is translated and implemented to organise and control all aspects of the construction and activity of living systems. PMID- 2586348 TI - [The stimulating effect of N-nitroso-ethylurea on the biosynthetic ability of Aspergillus oryzae]. AB - The mutagenic action of N-nitroso-N-ethylurea (NEU) taken at shock and prolonged doses together on Aspergillus oryzae yielded 98% of populations with an elevated synthesis of proteolytic enzymes. The combined action of shock and prolonged NEU doses had an advantage over a shock pulse dose because the frequency of mutations rose 2-16 times and the populations accumulated proteolytic enzymes within the range of 9 to 24 activity units. As was shown using a certain number of populations selected at random, the elevated accumulation of proteolytic enzymes in the medium remained stable within eight generations. PMID- 2586350 TI - Possible uses of urinary neopterin and biopterin measurement. AB - The measurement of urinary neopterin and biopterin may be an important non specific diagnostic tool. Urinary biopterin has been found to be decreased in parkinsonian patients, and in hyperphenylalanemia as a variant of phenylketonuria. Urinary neopterin has been found to be elevated in numerous conditions. It has been shown to be significantly higher in AIDS patients than in ARC patients, and significantly higher in ARC patients than in controls. Urinary neopterin has been shown to be prognostically elevated in a wide range of neoplasias, including multiple myeloma, hematologic and gynecologic neoplasias. Neopterin is thought to be an in-vitro indicator of activation of the immune system. PMID- 2586352 TI - DNA methylation and the regulation of gene expression. AB - An inverse relationship between a eukaryotic gene's level of methylation and its level of expression has long been recognized, and generally believed to result from reduced binding of postulated activator proteins to methylated target DNAs. There are, however, some genes where there is no apparent correlation between levels of methylation and gene expression, and even a small class where gene activation is correlated with increased methylation of the DNA. I propose a unifying hypothesis to explain these apparently divergent cases: methylation acts to reduce or abolish binding of regulatory proteins to their DNA target sites. In the majority of genes, methylation acts to block binding of activating factors; "indifferent" genes lack such methylation sites, while the minority class, which is more active when methylated, contains methylation sites which block binding of repressor proteins. PMID- 2586351 TI - Carrier presentation: a possible strategy for selective in vivo amplification of specific T cells. AB - A strategy for selective in vivo amplification of specific T cells by carrier presentation is outlined here. This hypothesis addresses the possible physiological significance of expression of MHC II molecules by T cells, and attempts to highlight the possibility of harnessing the phenomenon for therapeutic use in medicine. PMID- 2586353 TI - Does heat damage fetuses? AB - Temperature affects phenotypic variation during critical developmental stages in all forms of life that have been studied thus far. In animal studies of heat teratogenicity, adverse effects have ranged from disruption of the normal cell cycle leading to decreased numbers of cells, to the induction of developmental abnormalities by means of embryonic cell death. The heat shock response is a universal cellular stress reaction in which the transcriptional and translational mechanisms of the cell are pre-empted by preferential induction of heat shock protein synthesis. Occurrence of such a phenomenon during prenatal life could lead to the absence of essential gene products at critical stages of development. The crucial question of whether temperature induced cellular and genetic effects ever occur during human fetal development has been considered only in relation to maternal hyperthermia, which is generally viewed as not being of significance in human teratology. We propose that teratogenicity may result from fetal hyperthermia unrelated to maternal hyperthermia, caused either by impaired fetomaternal heat dissipation due to reduced placental blood flow (extrinsic fetal hyperthermia) or by increased fetal heat production during hypermetabolic states (intrinsic fetal hyperthermia). The need for further studies in this regard is emphasized. PMID- 2586354 TI - Does osteoporosis related to cytostatic drugs exist? AB - Osteoporosis has rarely been related to the use of cytostatic drugs. We report the case of a patient with chronic myeloid leukemia who presented several non traumatic vertebral fractures, most likely related to the use of Busulfan. This occurrence inclines us to propose further investigation of this rare adverse reaction. PMID- 2586355 TI - [Strict abstinence]. PMID- 2586356 TI - [Inhalation devices. Principles of design and areas of use]. PMID- 2586357 TI - Antimicrobial prophylaxis in surgery. PMID- 2586358 TI - Disposition of oral methotrexate in children with acute lymphoblastic leukemia and its relation to 6-mercaptopurine pharmacokinetics. AB - We studied the disposition pharmacokinetics of methotrexate (MTX) given orally to 16 children with acute lymphoblastic leukemia (ALL) and its relation to the pharmacokinetics of 6-mercaptopurine (6MP) in the same children. There was an eightfold variability in area-under-concentration time-curve (AUC) of MTX achieved by the same dose. Excellent correlation existed between peak concentrations and AUC0----infinity (r = 0.95, P less than 0.001). Elimination T1/2 was between 1.34 and 5 hours (mean 2.16 +/- 0.23 hr, mean +/- SE). A weak correlation existed between AUC achieved by 1 mg/m2 MTX and patients' age or body weight. Weak but significant correlation existed between AUC achieved by 1 mg/m2 of MTX vs. 6MP (r = 0.54, P less than 0.05). In 13/16 patients peak concentrations were achieved at 60 minutes. There was a significantly larger AUC of 6MP achieved by a standardized dose in longer therapy (greater than 15 mo) vs. short therapy (less than 12 mo) (462 +/- 75 and 246 +/- 58 ng.ml-1.min.mg-1.m2, P less than 0.025). No statistical differences in AUC of MTX were found between short and long therapy. The large interpatient variability in MTX pharmacokinetics supports the possibility that differences in absorption and/or clearance of the drug may affect the clinical response. Because of the excellent correlation between peak and AUC of MTX, and because 3 measurements, at 30, 60, and 90 minutes will almost invariably identify the peak, this measurement can be used to estimate AUC for purpose of correlation with clinical outcome. PMID- 2586360 TI - Psychosocial status of young adult survivors of childhood cancer: a survey. AB - The majority of childhood cancer patients now can expect to survive into early adulthood, cured of their cancer. Current adult survivors are a diverse group in terms of diagnosis, age at diagnosis, and types of treatment. It is estimated that by 1990, 1 in every 1,000 twenty-year-olds will have had cancer, making it important to describe the long-term psychosocial adjustment of this population. Patients who were diagnosed between 1948 and 1975 while less than 16 years of age, who were currently 18 years or older, had been off therapy for at least 5 years, and had no known brain damage were eligible for this survey and were identified through the tumor registry at the Children's Hospital of Philadelphia (CHP). Initially, the parents were contacted by letter. Ninety-five (57%) of the 167 eligible patients participated in a telephone interview, which covered educational achievement, occupational status, interpersonal relationships, marital status, pregnancies, employee benefits and insurance, and medical and health behaviors. Respondents were not different from nonrespondents in terms of sex, year of diagnosis, age at diagnosis, diagnoses, stage of illness, or type of treatments. There were no differences in terms of education, marital status, fertility issues, or occupational status by diagnosis group, age at diagnosis, or treatments. The patients were compared to siblings over 18 years of age in terms of education and marital status. No significant differences in sex distribution or years of education between patients and siblings were found. The siblings were, as a group, older than the patients and were more likely to be married. In general, these patients were functioning normally, but there are many unexplored areas of interpersonal relationships and productivity that need further study before conclusions regarding psychosocial adjustment of childhood cancer survivors can be drawn. PMID- 2586359 TI - Continuous infusion of recombinant interleukin-2 and lymphokine-activated killer cells in refractory malignancies. AB - Adoptive immunotherapy with recombinant interleukin-2 (rIL-2) and lymphokine activated killer (LAK) cells has been reported to effect the regression of tumor in patients with a variety of malignancies. Responses have occurred in patients treated with high-dose bolus rIL2 as well as lower-dose continuous intravenous infusion. Ten patients who had been extensively pretreated with systemic chemotherapy with or without additional radiation therapy were treated with continuous infusion rIL2 and LAK cells. Five patients received rIL2 alone for 96 120 hours prior to leukapheresis in addition to rIL2 at the time of LAK cell infusion. Three patients received LAK cells that had been cultured for 14 days in an automated tissue culture system. No responses were seen in this ten-patient cohort. While the lack of response in these patients may be related to any one or more of several variables, patients who have been heavily pretreated may not respond as well as patients who have received little to no systemic chemotherapy. PMID- 2586361 TI - Eight-drugs-in-one-day chemotherapy in postirradiated adult patients with malignant gliomas. AB - Fifteen patients, 12 with glioblastoma multiforme and 3 with anaplastic astrocytoma, were treated with "eight-drugs-in-one-day" chemotherapy [methylprednisolone 300 mg/m2, vincristine 1.5 mg/m2 (maximum of 2 mg/cycle), CCNU 75 mg/m2, procarbazine 75 mg/m2, hydroxyurea 3,000 mg/m2, cisplatin 90 mg/m2, cytosine arabinoside 300 mg/m2, and imidazole carboxamide 150 mg/m2]. All patients had prior brain irradiation but none had previous chemotherapy. The population included 10 patients with progressive disease after irradiation and 5 who presented within 2 months of completing radiation. Patients received an average of 5 monthly cycles of chemotherapy. Three patients achieved a complete and 2 a partial response (CR + PRrate was 33%). The median survival time was 46 weeks. Myelosuppression was the dose-limiting toxicity. Leucocyte counts between 2.0-4.5 x 10(3)/mm3 were observed in 40% of patients, between 1.0- less than 2.0 x 10(3)/mm3 in 33%, and less than 1.0 x 10(3)/mm3 in 7%. Platelet counts between 50-130 x 10(3)/mm3 were observed in 27% of patients, and less than 50 x 10(3)/mm3 in 33%. Six patients suffered infections, 4 had reversible renal toxicity, 2 developed paresthesias, and one a debilitating myopathy related to treatment with dexamethasone. Ototoxicity was seen in 3 patients. Two patients developed pulmonary emboli. Nine patients had nausea and vomiting, in one case associated with Candida esophagitis. One long-term survivor developed necrosis of the corpus callosum and dementia. Four patients discontinued treatment after an average of 3.5 cycles because of toxicity. Although extremely toxic, this regimen has modest activity in previously irradiated adult patients with malignant glioma. PMID- 2586363 TI - Keloids and neoplasms in the Rubinstein-Taybi syndrome. AB - In a series of 574 individuals with the Rubinstein-Taybi syndrome, 28 had keloids, and 19 had one or more neoplasms. The array of malignant neoplasms does not suggest an etiology or pathogenesis in common. One possible exception is that four cases of leukemia were observed. When the data for malignant and benign neoplasms were combined, at least nine of the 22 could have arisen from developmental errors. The apparent excess of keloid formation indicates overreaction to mild injury, with no known relevance to neoplasia but of potential interest in future studies of scar formation. PMID- 2586364 TI - Multiple hemangioendotheliomas of the liver. PMID- 2586362 TI - Second malignant neoplasms following childhood Hodgkin's disease: treatment and splenectomy as risk factors. AB - The risk of second malignant neoplasm (SMN) was evaluated in 979 children with Hodgkin's disease. This cohort was diagnosed between 1955 and 1979 at one of the institutions of the Late Effects Study Group. Solid tumors, non-lymphocytic leukemia, and non-Hodgkin's lymphoma (NHL) developed in 18, 17, and 3 patients, respectively. The estimated cumulative probability of developing any SMN was 2% at 5 years from diagnosis, 5% at 10 years, and 9% at 15 years. The incidence is ninefold greater than the risk of acquiring cancer in 19 year-olds, the median age at which the diagnosis of SMN was made in this study population. For leukemia and NHL the corresponding probabilities were 1%, 3%, and 4% for the group as a whole but were increased (2%, 6%, and 8%) in patients who had suffered one or more recurrences. In order to analyze the risk of leukemia and NHL associated with alkylating agent chemotherapy, each patient was assigned a score of one for each alkylating agent administered for a 6-month period. Scores of 2, 4, 6, and 8 were associated with probabilities of leukemia or NHL of 2%, 3%, 6%, and 10%, respectively. In a multivariate analysis for leukemia/lymphoma that included AAD score, stage, and splenectomy, the effect of AAD score and splenectomy did not change substantially compared to the univariate results. AAD score remained statistically significant (P = .0001), and splenectomy was of borderline significance (P = .09). Of the 18 solid tumor SMNs, 15 developed within the field of radiation, and one other developed in tissue irradiated 34 years earlier for hemangioma. This study of a large and unselected group of children with Hodgkin's disease who received a variety of therapies demonstrates that children are as likely as adults to develop acute leukemia after alkylating agents and solid tumors in the field of radiation therapy. PMID- 2586365 TI - Lung cancer in childhood. AB - A 16-year-old boy had unresolving right lower lobe consolidation due to primary adenocarcinoma of the lung. Lung cancer is rare in children, is usually adenocarcinoma or undifferentiated histology, and frequently presents with advanced disease. It may be confused with atelectasis attributable to a foreign body or bronchial adenoma, plasma cell granuloma, pulmonary sequestration, or chronic infection. We review the clinical features of pediatric lung cancer and differences in lung cancer between children and adults. PMID- 2586366 TI - Successful treatment of a radiation-associated extradural osteosarcoma with chemotherapy in an adolescent girl. AB - Bone sarcomas are the most common second malignant neoplasms in survivors of a malignant solid tumor in childhood. In contrast to de novo tumors, secondary bone cancers are typically associated with a poor prognosis, reflecting both a preponderance of primary sites that preclude complete resection in the flat bones of the axial skeleton, and the tendency for local invasiveness or distant metastasis. We describe a patient who developed malignant extradural osteosarcoma of the temporal bone 6 years after successful treatment for a malignant cerebellar astrocytoma with surgical resection and local irradiation. A complete resection of the sarcoma was not possible; however, she achieved a biopsy-proven complete response after intensive chemotherapy with ifosfamide, followed by cisplatin and doxorubicin. At age 13, she remains free of recurrence 3 years after completing all therapy. In view of the rarity of prolonged disease control after incomplete resection for osteosarcoma, this report suggests the value of intensive combination chemotherapy in achieving a durable unmaintained remission in our patient. PMID- 2586367 TI - Double autologous bone marrow transplantation for acute myelogenous leukemia in a patient treated for Hodgkin's disease. AB - A 30-year-old man developed acute myelogenous leukemia nearly 3 years after treatment of Hodgkin's disease with radiation and three chemotherapy combinations. Remission was induced with one cycle of high-dose Ara-C therapy. Three cycles of consolidation chemotherapy were given. The patient then had two autologous bone marrow transplants, the first after conditioning with 5 Gy total body irradiation, the second after Melphalan 140 mg/m2. The procedures were well tolerated, although hematological reconstitution was very slow after the second autotransplant. The patient has been disease-free for over 4 years. Such patients may be more vulnerable to transplant-related complications because of their previous exposure to chemotherapy and radiation, which may damage several organs including the bone marrow. This report demonstrates that patients with secondary acute myelogenous leukemia may tolerate a double autotransplant procedure and achieve durable remissions. PMID- 2586368 TI - The 1989 Coolidge Award address. A tribute to teachers. PMID- 2586369 TI - A comparison using tissue electrical properties and temperature rise to determine relative absorption of microwave power in malignant tissue. AB - This paper compares two methods for determining the radio frequency absorbed power in tissue: from the measured electrical properties of the tissue, and from the induced temperature rise per unit time. In previous research, we measured the ratio frequency electrical properties of muscle, mammary gland, and malignant mammary tissue (SMT-2A mammary adenocarcinoma) in female W/Fu isogeneic rats. From those measurements we calculated for each tissue the power absorption versus frequency, and formed the ratio of malignant-to-normal power absorption. This ratio exhibited a peak within the 150 to 400 MHz range, indicating a selective absorption of power in this type of malignant tissue over that of the normal host tissue. In the present study, by an entirely different method, we have directly tested the results of our earlier research. We filled a 20-cm-long section of rigid coaxial line (ordinarily air filled) with either normal (beef muscle or fat) or malignant (SMT-2A) tissue, and measured the temperature increase versus time at the irradiated tissue surface for the same absorbed power in each tissue type. We made the measurements from 50 to 915 MHz, and found that the initial temperature increase per second per watt absorbed (dT/dt/Pa) was greater in malignant tissue than in muscle or fat at each frequency tested, with the greatest differences occurring below 450 MHz. Power absorption based on the measured values of dT/dt/Pa was again greatest for the malignant tissue (SMT-2A mammary adenocarcinoma) within the 150 to 400 MHz range. PMID- 2586370 TI - Real-time distortionless high-factor compression scheme. AB - Nowadays, digital subtraction angiography systems must be able to sustain real time acquisition (30 frames per second) of 512 x 512 x 8 bit images and store several sequences of such images on low cost and general-purpose mass memories. Concretely, that means a 7.8 Mbytes per second rate and about 780 Mbytes disk space to hold a 100-s cardiac examination. To fulfill these requirements at competitive cost, a distortionless compressor/decompressor system can be designed: during acquisition, the real-time compressor transforms the input images into a lower quantity of coded information through a predictive coder and a variable-length Huffman code. The process is fully reversible because during review, the real-time decompressor exactly recovers the acquired images from the stored compressed data. Test results on many raw images demonstrate that real time compression is feasible and takes place with absolutely no loss of information. The designed system indifferently works on 512 or 1024 formats, and 256 or 1024 gray levels. PMID- 2586371 TI - Quantitative measurement of small-angle gamma ray scattering from water, nylon, and Lucite. AB - The small-angle (2 degrees-10 degrees) total-differential-scattering cross sections of water, methyl methacrylate, and nylon 6 have been measured at a photon energy of 59.54 keV. An annular target geometry has been used with an acceptance of +/- 0.5 degrees and an experimental uncertainty of approximately 4% achieved. The experimental methods and data corrections necessary to obtain this accuracy are discussed in detail. The results demonstrate clearly the contribution of intermolecular effects to the scattering process and allow critical comparison with calculations using molecular form factors for water obtained from interpolated x-ray diffractometer data; agreement is obtained within the experimental uncertainties. They also support earlier Monte Carlo predictions of scattering in water at angles of the order of 2 degrees which are in disagreement with certain published experimental data. PMID- 2586372 TI - Performance characteristics of a real-time digital x-ray fluoroscopic system using an intensified charge injection device camera and CsI:Na crystal. AB - A digital x-ray photoelectronic imaging system has been constructed using an optically flat 152-mm-diam, 2.5-mm-thick CsI:Na scintillating crystal. X-ray images formed by the scintillator are viewed by a single microchannel plate intensified charge injection device (ICID) camera and digitized at a real-time rate by a computerized frame-grabbing system. Video images are recorded and selected image frames are subjected to image processing and analysis schemes. Parameters governing the performance characteristics of the system are determined accordingly. For a 152-mm field size at the crystal plane, a spatial resolution limit of 1.50 +/- 0.10 1p/mm (1 sigma) measured at the 4% level of the modulation transfer function of the system has been obtained. This result is consistent with the measurements of the full width at half-maximum of the line spread function which is found to be 645 +/- 35 microns (1 sigma). Similarly, the intrinsic resolution of the CsI:Na scintillator only was found to be 6.5 +/- 0.5 1p/mm (1 sigma). Contrast ratio measurements, which are mainly determined by the quality of phosphor, have indicated a value of 12.1 +/- 0.6, whereas minimum visible details are observed at radiation exposure rates of 100 microR/s. This limit has been reduced to 10 microR/s using the single-scan integrating option provided by the ICID camera. A maximum contrast resolution of 1% corresponding to 100 statistically significant meaningful gray levels is achieved at a maximum exposure rate of 1000 microR/s. Consequently, although the imaging capability of the present system compares favorably with that of conventional x-ray video fluoroscopic systems, a better performance may be achieved by using a higher resolution cooled dual-microchannel intensified CID camera in conjunction with a thinner CsI:Na crystal and a real-time digital image processing subsystem. PMID- 2586373 TI - A correlated noise reduction algorithm for dual-energy digital subtraction angiography. AB - It has long been recognized that the problems of motion artifacts in conventional time subtraction digital subtraction angiography (DSA) may be overcome using energy subtraction techniques. Of the variety of energy subtraction techniques investigated, non-k-edge dual-energy subtraction offers the best signal-to-noise ratio (SNR). However, this technique achieves only 55% of the temporal DSA SNR. Noise reduction techniques that average the noisier high-energy image produce various degrees of noise improvement while minimally affecting iodine contrast and resolution. A more significant improvement in dual-energy DSA iodine SNR, however, results when the correlated noise that exists in material specific images is appropriately cancelled. The correlated noise reduction (CNR) algorithm presented here follows directly from the dual-energy computed tomography work of Kalender who made explicit use of noise correlations in material specific images to reduce noise. The results are identical to those achieved using a linear version of the two-stage filtering process described by Macovski in which the selective image is filtered to reduce high-frequency noise and added to a weighted, high SNR, nonselective image which has been processed with a high frequency bandpass filter. The dual-energy DSA CNR algorithm presented here combines selective tissue and iodine images to produce a significant increase in the iodine SNR while fully preserving iodine spatial resolution. Theoretical calculations predict a factor of 2-4 improvement in SNR compared to conventional dual-energy images. The improvement factor achieved is dependent upon the x-ray beam spectra and the size of blurring kernel used in the algorithm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2586374 TI - Installation of an ambient-temperature control system in a 1.5-tesla whole body system to facilitate animal studies. AB - An ambient-temperature control system, designed to maintain small, anaesthetized animals at physiological temperatures during long examination times, is described. The system is suitable for installation in large bore, whole-body magnets and can be positioned close to the animal under study. Design details and a description of the equipment used is given. The system proved to be satisfactory in maintaining mice at physiological temperatures. PMID- 2586376 TI - [Genetically determined hepatosplenomegaly. A discussion by gastroenterologists in Freiburg]. PMID- 2586377 TI - [Kaposi sarcoma in HIV infection: a malignant tumor? Differential response to chemotherapy in relation to the site]. PMID- 2586375 TI - [Incidence of intravenous thrombolytic therapy and fatalities in patients with acute transmural myocardial infarct (Q infarct). A study of observations from 1984 to 1987]. AB - All patients admitted to the ICU with acute myocardial infarction (MI) were treated by the same protocol since 1984. We report the results in Q-wave-MI of 1987 compared to 1984. Age (67.2 +/- 12.4 vs. 66.8 +/- 11.4 years), sex distribution (70.1% vs. 71.9% male), time elapse between begin of symptoms and admittance to the hospital (15.5 +/- 27.0 vs. 15.0 +/- 32.5 hours) were similar in both years, but the total number of definite Q-MI decreased by 22% from 135 (1984) to 105 (1987). Inhospital mortality (20% vs. 23%) and ICU mortality (14% vs. 20%) tended to decrease, although differences did not reach statistical significance. This was paralleled by an increase in the rate of i.v. thrombolytic therapy from 17% (1984) to 28% (1987) of all patients with Q-MI. The percentage of patients who definitely received i.v. thrombolysis when all indication criteria were present and all contraindicatory factors excluded increased from 47% (1984) to 97% (1987). We conclude, that the performance of i.v. thrombolysis in all patients, who fulfill the general accepted criteria for thrombolysis may improve clinical course and outcome in a given population of patients with acute Q-wave-infarction. PMID- 2586378 TI - [Expected risk of congenital toxoplasmosis in Florence and its province. Statistical research in 1984]. AB - Research has been carried out to determine the prevalence of toxoplasma infection in 1176 women of fertile age in Florence and province for 1984 so as to calculate expected congenital foetal risk of toxoplasmosis. Prevalence proved to be 22% in women aged from 15 to 20 and 60% in the 41-45 group, with an average annual sero conversion rate of 1.5%. As pregnancy lasts 9 months, this rate is cut by 1/4, namely it drops from 1.5% to 1.125%. Transmission of the infection from mother to foetus occurs in about 1/3 of cases. 9256 pregnancies were reported in Florence and province. The expectation was therefore 104 primary infections and 35 infected newborns of whom 11-12 clinically diagnosable at birth. The estimated rate of toxoplasmosis in pregnancy is therefore 11% for Florence and foetal infection is about 4%. Two-thirds of the newborns with toxoplasma infection are asymptomatic but, if left untreated, they may develop serious neurological and behavioural sequelae. It is therefore necessary to learn the immune state with respect to toxoplasma for all fertile women before pregnancy and study negative findings during gestation. PMID- 2586379 TI - [Lipid profile in adiposity in children and adolescents]. AB - Lipid plasma levels were measured in a group of 251 adipose juveniles. Triglycerides were elevated in relation to age but not to weight excess. Cholesterol and LDL levels had a same behaviour, through childhood toward adolescence, with significantly higher values in males than in females. VLDL levels prove a significative increase in reference to BML rise, but not so much increasing age. In short, the juvenile adiposity doesn't seem to produce considerable alterations of lipidaemia incides, even if we can foresee a possible evolution toward an acclaimed dislipidaemic pattern in adulthood. PMID- 2586380 TI - [The value of determining anti-gliadin antibodies as well as carotene and xylose blood levels in various phases of celiac disease]. AB - The usefulness of measuring xylosaemia, carotenaemia and the antigliadin antibodies in the diagnosis and monitoring of coeliac diseases has been examined, 89 children, 57 with aspecific chronic diarrhoea and 32 with coeliachia were examined. The xylose proved less sensitive (80%) and less specific (84.2%) than carotenaemia (respectively: sensitivity 86.6% and specificity 87.7%). Nevertheless, considering the by no means negligible percentage of false positives and false negatives encountered with both techniques, it should be reiterated that these tests have a purely orientative value, whereas measurement of serum AGA may be considered a highly reliable investigation for selective children to be submitted to biopsy, considering the high sensitivity (AGA IgG 100%; AGA IgA 90.9%) and specificity (AGA IgG 85%; AGA IgA 100%) observed in the present series. PMID- 2586381 TI - [Congenital telangiectasic (pyogenic) granuloma of the anus: a rare location of a benign neonatal tumor]. AB - The neonatal anus is an unusual anatomic site for granuloma pyogenicum (GP). Several synonisms exist for GP (at least 16). It is a tumor of soft tissues (benign vascular tumor). Both a maternal variant (the epulis) and a hamartomatous perinatal one are known. The terms teleangiectasic granuloma and pyogenic or infected granuloma have been used to describe respectively the early and late stages of the lesion. In the anal site it appears as a sessile or peduncolated, red-wine, soft little tumor of the size of a millet or barley grain. Histologically it is a capillary haemangioma with inflammatory infiltrates in its soft connective tissue stroma and covered with thinned epidermis. During 1988 we have seen two cases in 2000 consecutive newborns, both in females. PMID- 2586382 TI - [Methods of research on the chromosome level in diagnosing genetic disorders]. PMID- 2586383 TI - New doctor on the block. Interview by Richard L. Reece. PMID- 2586384 TI - The life and times of today's house officers. Interview by Richard L. Reece. PMID- 2586385 TI - Current issues in bioethics. Demands, limits, and autonomy. PMID- 2586386 TI - Residency reform. Medicine examines its age-old rituals. PMID- 2586387 TI - HIV testing: counseling those at risk. PMID- 2586388 TI - Hospital-physician alliances in an evolving marketplace. PMID- 2586389 TI - Maintaining a professional ethic 'higher than law'. PMID- 2586390 TI - The state of nursing science. PMID- 2586391 TI - Substance abusing nurses appearing before the Board of Nursing. AB - Substance abuse among nurses is a problem of growing concern. In an effort to explore this problem, the authors investigated 122 files of substance abuse cases from the Mississippi State Board of Nursing from 1956 to 1984. Results of this analysis are presented and recommendations are suggested. Substance abuse is one of the major problems facing the general public today (Jarvis, 1980). It has been postulated that individuals more likely to become involved with drugs are those experiencing high stress levels in work situations. Nursing is considered by some to be one of the most stressful of all the health care profession. That nurses may have a special problem with substance abuse is becoming more evident. The National Council of State Boards of Nursing reported 971 substance abuse actions during a period from September 1980 through August 1981 (More Help, 1983). This study attempts to develop a profile of the substance abusing nurse in one state who was found guilty of substance abuse charges by the Board of Nursing. PMID- 2586393 TI - Ethical issues in neurologic practice. PMID- 2586392 TI - Nursing students aid disaster victims. PMID- 2586394 TI - Moral theory and neurology. AB - This article presents an outline of a general moral theory and shows its relationship to the concepts of paternalism and that of valid consent and refusal. The authors then show how this theory and these concepts can be usefully applied to the moral problems that neurologists often face in determining how to act when they have distressing information for their patients. Finally, a procedure is provided for determining when it is morally justified to deceive patients by withholding information about their diagnoses, prognoses, or about their prospective treatments. PMID- 2586395 TI - The neurologist as ethics consultant and as a member of the institutional ethics committee. The neuroethicist. AB - Because of the increasing number of neuroethical dilemmas in medicine, neurologists are becoming more involved with the activities of institutional ethics committees and also serving as ethics consultants. This article discusses the role and functions of a "neuroethicist" and gives common clinical examples that illustrate how a neurologist can be of value in these neuroethical dilemmas in the clinical setting. PMID- 2586396 TI - Ethical issues in brain death and multiorgan transplantation. AB - There is a consensus in Western society that "brain death" is the medical and legal standard for human death. Patients in persistent vegetative states may have lost their "personhood," but they are not dead. It may be desirable to maintain the physiologic processes of a brain-dead pregnant woman to permit the birth of her child. The determination of brain death and plans for multiorgan transplantation should be conducted independently. It is axiomatic that the multiorgan transplantation donor must be dead. Therefore, living anencephalic infants and patients in persistent vegetative states cannot be organ donors. It is permissable to temporarily maintain the physiologic processes of brain-dead patients in order procure their organs for transplantation. Society will have to decide if money spent on multiorgan procurement and transplantation is better spent in other areas of health care. PMID- 2586397 TI - Ethical issues in the use of anencephalic infants as organ donors. AB - For many, the ethical issues raised in the previous sections are sufficient to justify opposition to tampering with either the dead-donor rule or the definition of death in general and the use of anencephalic infants as organ donors in particular regardless of how many organs could be procured. Others will see it as a question of balancing the relative costs and benefits of the proposal. Given, the likely bad consequences and meager benefits, these protocols are difficult to justify on those grounds as well. The proposals of waiting until brain death has occurred also pose some serious, though not necessarily insurmountable, ethical problems. With supportive care, however, anencephalic infants do not become brain dead in the first week of life. Given the declining incidence of anencephaly, the issue regarding anencephalic infants will probably become moot in the next few years. As the need for organ donors continues to grow, we will undoubtedly be faced with future proposals to harvest vital organs from other "unique" categories of dying or severely impaired patients. We believe that the current dead donor rule and the strict "whole-brain" definition of death are sound public policy and good ethics and should remain the cornerstone of future decisions in this field. PMID- 2586398 TI - Neural fetal tissue transplantation. Should we do what we can do? AB - The following factors are relevant to ethical considerations regarding fetal tissue transplantation for treatment of neurological disorders: the empirical status of human fetuses or abortuses, different purposes and sites of tissue retrieval or implantation, the therapeutic potential of the technique, the means through which tissue becomes available, possible motives, and possible donors and recipients of transplant tissue. After examining each of these, the author concludes that (1) only dead fetuses should be used as tissue sources, (2) decisions regarding abortion and transplantation should be kept separate, (3) anonymity between donor and recipient should be observed, and (4) buying and selling of fetal tissue should not be permitted. PMID- 2586399 TI - Decisions to withhold or terminate treatment. AB - Decisions to withhold or terminate treatment are common clinical dilemmas in patients dying from diseases of the nervous system. Decision making for such patients must be based upon ethical principles. Under the doctrine of valid consent and refusal, competent patients have the right to refuse life-sustaining therapies. For incompetent patients, this right may be exercised through their previously executed advanced directives or through appointed proxy decision makers. Physicians have the duty to assess the potential benefits and harms of various treatment options and to clearly communicate this information to patients and their proxies in a supportive manner. The authors illustrate the application of ethical principles in neurologists' management of patients in persistent vegetative states, dementia, and end-stage neuromuscular disease. PMID- 2586400 TI - Legal aspects of termination of treatment decisions. AB - A large body of medical and ethical opinion holds that it is justifiable to terminate medical treatment for permanently unconscious persons. But opponents of particular decisions to withhold or withdraw treatment may argue that the decisions violate laws against homicide, pose a threat to the lives of other less severely afflicted persons, rest on uncertain diagnoses or prognoses, proceed without adequate knowledge of individual preferences or interests, or have an adverse impact on the values of physicians and other health care providers. Although laws differ among the states, decisions that derive from rigorous clinical evaluations and carefully achieved agreements between medical caretakers and lawful proxies of afflicted persons about appropriate levels of care should be defensible against various forms of legal attack. PMID- 2586401 TI - Starting and stopping the ventilator for patients with amyotrophic lateral sclerosis. AB - Only a minority of patients who have ALS require, request, and receive assisted or supported ventilation. Usually, when a mechanical ventilator is needed, nonsurgical methods can be used for prolonged periods of time. Appropriately timed discussions can reduce the need for emergency management of breathing failure. The doctrine of informed consent applies to decisions about life support. It involves both the physician (to exercise clinical judgment on behalf of the patient) and the patient (to make personal decisions). They must interact. The patient's firm decision must be clear but need not be in the form of a "living will," and it does not need to be sought repeatedly or reiterated endlessly. Just as a considered decision cannot be arbitrarily overthrown in a time of crisis, neither can a change of mind be willfully ignored. In practice, this may test the capability of even the most experienced and understanding physician, and may result in less-than-ideal outcomes, as our examples show. As in any other area of medical practice, personal experience teaches valuable lessons. Unfortunately, even extended publications discussing clinical management of ALS have failed to address the subject of discontinuing ventilatory support, and ethicists have not always been helpful. Bernat and Beresford have, however, successfully summarized the ethical issues involved. Failure to sustain breathing mechanically or withdrawing artificial support of breathing from a requesting patient who, in the terminal stage of ALS, has become unable to breathe without a mechanical ventilator cannot be called assisted suicide, mercy killing, or either passive or active euthanasia. It is allowing a competent person to die naturally of the incurable illness that afflicts him. The state has no legal interests to be served by intervening in the process just described, which bears no relationship to issues of malpractice, much less to criminal negligence or homicide. Neurologists have not uniformly understood these points, as demonstrated by previous publications addressing the issue and by the findings of our own survey of neurologists who have special experience in the area of neuromuscular diseases. In regard both to starting and to stopping the ventilator, we believe strongly that it is time to lay aside the moral, legal, and ethical conflicts that have needlessly delayed or prevented physicians from complying with the resolute decisions that competent patients have made about their own lives. We urge doctors to act in these cases, as in all others, with their best medical judgment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2586402 TI - Selective nontreatment of neurologically impaired neonates. AB - We are convinced that a best-interests approach is the best approach to take in making decisions to treat or not to treat disabled young infants. Such an approach acknowledges that there are some medical conditions that are so severe that efforts to sustain the lives of infants having the conditions cannot be said to be in the best interests of those infants. By paying attention to the variables that compose the best-interests approach, decision makers can arrive at decisions not to sustain life that are more easily justifiable than with any other approach. PMID- 2586403 TI - Early prognosis in anoxic coma. Reliability and rationale. AB - As desirable as it might be to predict early in the course of coma whether a patient will do well or poorly, all studies of coma prognosis are plagued by inherent methodologic problems that tend to diminish the utility of the derived criteria: especially the tendency of poor prognoses to be self-fulfilling, the rapid drop-off in patient population due to death from nonneurologic causes, and the need to lump, for the sake of statistical significance, outcome categories that ought to be kept distinct for purposes of ethical decision making. Even for a methodologically ideal study, if 100 per cent of the N patients fulfilling a particular criterion experienced the same poor outcome, the probability of a false prediction of poor outcome in the next patient meeting that criterion is approximately 1/(N + 2), which is hardly negligible for a realistically sized study. Moreover, there is a 50 per cent chance of at least one false-positive prediction among the next (N + 1) patients fulfilling the criterion. Given this inherent unreliability of early predictors for individual patients, given that decisions to continue life support are reversible, whereas decisions to withdraw it are usually not, and given that the death of a patient with potential for recovery is a more serious error than the (typically) transient prolongation of life of a patient destined soon to die anyway or (much less commonly) to remain in a chronic vegetative state, it would seem prudent to continue life support for all patients during the first few weeks or months of coma or vegetative state, regardless of early indicators of poor outcome. Early prognostication can still serve other useful purposes, however, including the counseling of families, triage and DNR decisions, and future clinical investigations of brain resuscitative measures. PMID- 2586404 TI - Ethical aspects of medical economics. AB - The fundamental problem of economics is how best to satisfy human needs and desires in the face of limited resources. Any benefit achieved by expending resources for one purpose is offset by an "opportunity cost": The opportunity to use those resources for other purposes is lost. Whenever resources are used to provide one medical benefit, a choice is made not to provide other benefits. The opportunity costs of medical care choices are rarely acknowledged; thus the ethical implications of such choices are rarely explicitly stated. Rationing of medical care is inevitable; how to ration our resources must be openly debated within an ethical framework. Individual physicians have an ethical obligation to avoid wasteful and unnecessary expenditures of the resources allocated to medical care. Society has an obligation to confront the ethical dilemmas implicit in health care allocation and rationing decisions. Although perhaps less painful, avoiding difficult choices is less ethical than confronting them. PMID- 2586405 TI - Shared responsibility for staff assignment. PMID- 2586406 TI - [Surgery of lung cancer and the clinical application of basic studies]. AB - We performed several basic studies concerning lung cancer and their results were applied clinically. One was the establishment of cultured lung cancer cell strains and they were employed for sensitivity tests of anticancer agents and to study histogenesis of oat cell carcinoma and monoclonal antibody. Another study was the experimental induction of lung cancer in dogs. We succeeded in inducing canine central type lung cancer. Using epithelial cells from the various stages recognized in the carcinogenetic process. We measured DNA distribution and nuclear protein amounts, and we indicated the relationship between the carcinogenetic process and DNA pattern. Among 2,633 lung cancer cases 1,072 were resected. The 5-year survival of the latest 384 resected cases was 80.3% in stage I. The reasons for this relatively high survival rate is probably because of increased numbers of early stage central type lung cancer due to increasing sputum cytology surveys. Adjuvant therapy was performed using nocardia rubra cell wall skeleton and/or chemotherapy with CDDP. However, significantly better results were not obtained. The surgical results were discussed in 425 cases aged 70 years and over. The therapeutic results and indications of photodynamic therapy in early stage central type lung cancer were presented. PMID- 2586407 TI - [Recent trends in breast cancer surgery in Japan]. AB - In the past ten years, extended or conventional radical mastectomies have decreased, being replaced by modified radical mastectomies (muscle-preserving mastectomies) such as Auchinoloss' operation and Patey's operation. Furthermore, limited surgeries for early cases such as partial mastectomy, lumpectomy etc. also have increased in the recent three years. The indications for these operations, the surgical techniques, postoperative functional and cosmetic problems were presented. And future problems as to partial mastectomy were also discussed. In contrast, aggressive surgery such as extensive resection of the chest wall for locally advanced breast cancer is useful as one of the therapeutic measures in the recent multidisciplinary treatments for breast cancer, in order to prolong the patient's survival and improve the quality of life. The techniques including the reconstruction using musculocutaneous flaps were also presented. PMID- 2586408 TI - [Blood flow disturbance in digestive organs--a viewpoint of vascular surgery]. AB - Various blood flow disturbances in intraabdominal digestive organs were studied clinically and experimentally from a viewpoint of vascular surgery. Acute gastric mucosal lesion may occur due to ischemia and reperfusion injury of the gastric mucosa. Bleeding from stomach ulcer may be rarely caused by consumption coagulopathy along with aortic aneurysm. Heparin therapy was successful to interrupt it. Gastrectomy is not indicated for such condition but aneurysm should be repaired. Portal vein reconstruction for the radical resection of hepatic, biliary and pancreatic cancers should be carefully made, because early or late stenosis occurs frequently, and they may connect to early or late morbidities or mortalities. On the other hand, resection and replacement of the suprarenal vena cava invaded by the retroperitoneal malignant tumor may be safely carried out. For the acute mesenteric arterial occlusion, early diagnosis and arterial reconstruction are essential to save catastrophe. Positive Doppler sound on the vasa recta seems to be the most reliable parameter for assessing bowel viability. Approach from the proximal large arteries is recommended for uncontrollable intraperitoneal bleeding. PMID- 2586409 TI - [Rationalization of lymph node dissection for gastric cancer using small sized activated carbon particles adsorbing absolute ethanol]. AB - CH40 is five percent saline solution of the activated carbon particles with 20nm in diameter. It can absorb a large amount of ethanol. CH40 reach to the regional lymph nodes immediately after local injection, visualize the regional lymph nodes black in color and release ethanol in the metastatic lymph nodes. As the direction of lymph nodes staining was coincident with direction of metastasis, rationalization of lymph nodes dissection could be performed as follows: 1) When lymph nodes metastasis are found along the lesser curvature, dissection of lymph nodes in the hepatoduodenal ligament should be carried out. 2) When lymph nodes metastasis are found in the infrapyloric region, dissection of lymph nodes along the splenic artery, in the hepatoduodenal ligament, at the posterior aspect of the pancreas, and at the root of the mesenterium should be carried out. 3) When lymph nodes metastasis are found along the left gastric artery, the common hepatic artery, or the splenic artery, dissection of para-aortic lymph nodes should be carried out. PMID- 2586410 TI - [The indication for lymph node dissection around abdominal aorta in gastric cancer]. AB - In 77 cases with gastric cancer, for which lymph node dissection around the left renal vein was performed in the past 5 years, the sites and routes of metastasis were investigated to determine the indication for dissection around the left renal vein. The rate of metastasis to the lymph nodes around the left renal vein was 23.4%. The typical routes of metastasis were 1) the left lower phrenic route, 2) via the splenic artery, 3) via the celiac artery, 4) via the superior mesenteric artery and 5) the postpancreatic route. Dissection was considered to be indicated for the patient with N2 or more distant lymph node involvement and for cases with carcinoma of the upper part of the stomach or whole stomach with N2 positive lymph node. It was also indicated for N3(+) cases or No. 9(+) cases of carcinoma of the middle and lower parts of the stomach. Needless to say the absence of other non curative factors is required. PMID- 2586411 TI - [Reasonable lymph node dissection in radical gastrectomy for gastric cancer: introduction of computer information system and lymphography technique by India ink]. AB - A computer information system was developed and clinically used in National Cancer Center Tokyo in 1983. Seven data of an individual patient are preoperatively input in the system: sex, age, location, macroscopic type, maximal diameter, depth of invasion, and histological type of biopsy. After the data analysis of 3,785 patients, the computer outputs three data; expected five year survival rate, each metastatic rate of 16 regional lymph nodes, and types of recurrence. Plan of lymph node dissection can reasonably be decided by this report. 0.5ml of India-ink (CH-40) is injected in the perigastric lymph nodes, and it stains all lymphatic channels from the injection points in black. Using the technique, systematic dissection can be performed easily and completely. After the introduction of these systems, five year survival rate was improved from 90.0% to 95.5% in Stage I, from 76.0% to 81.6% in Stage II, from 51.1% to 56.8% in Stage III, and from 12.9% to 16.6% in Stage IV. PMID- 2586412 TI - [Rational surgical operations for advanced cancers located in the middle of the stomach]. AB - Before 1982, total gastrectomy with pancreaticosplenectomy was performed for advanced gastric carcinoma which exposed to the serosa and was located in the middle of the stomach (M). The results of that surgical treatment were evaluated, and new surgical approaches were expected to provide a much better prognosis to patients. (1) A radical surgical operation, left upper abdominal evisceration + Appleby's method (LUAE + Apl), was tried for Borrmann type 4 gastric cancers from 1983. The 3-year survival after LUAE + Apl (77.9%) was better than that after total gastrectomy with pancreaticosplenectomy (35.0%) (p less than 0.05). In terms of the postoperative condition, no significant differences were observed between both operations. (2) As a conservative operation, total gastrectomy with resection of the spleen and splenic artery (Group A) was compared with total gastrectomy plus pancreaticosplenectomy (Group B) in patients with advanced gastric carcinoma other than Borrmann type 4. The 5-year survival was similar in both groups. The incidence of postoperative disorders was lower in Group A than in Group B (p less than 0.05). LUAE + Apl for Borrmann type 4 and total gastrectomy with resection of the spleen and splenic artery for the other advanced gastric cancers led to good results. These rational surgical operations will be necessary to achieve a good quality of life for the patients. PMID- 2586413 TI - [Indications for total gastrectomy combined with pancreaticosplenectomy in the treatment of middle gastric cancer]. AB - Of 1725 patients with middle gastric cancer (M, MA, MC) on whom radical surgery was performed (except for absolute non-curative resection) from 1960 to 1984 at the Cancer Institute Hospital, 238 patients in whom total gastrectomy or proximal partial gastrectomy combined with pancreaticosplenectomy was carried out, were submitted for both clinico-pathological and prognostic examination. The following results were obtained: 1. There are few indications for total gastrectomy plus pancreaticosplenectomy in patients with middle gastric cancer in which the lesions are superficial or semi-superficial. 2. For patients in whom the cancer occupies portions of the greater curvature, on posterior wall of the stomach, the whole stomach, or is of a non-localized type, the metastatic rate of lymph nodes No (10) or lymph nodes No (11) is high, then total gastrectomy plus pancreaticosplenectomy should be considered. 3. Lymph nodes No (2), (4d), (4sb) (7) and (9) can be good indices indicating presence or absence of metastasis of lymph nodes No (10) and lymph nodes No (11). 4. Radical surgery as well as effective adjuvant therapy are required for gastric cancer with invasion of the serosa. PMID- 2586414 TI - [The effectiveness of Appleby's operation in advanced gastric carcinoma]. AB - This study was undertaken in order to evaluate the effectiveness of Appleby's operation on the postoperative survival rate as compared with that of conventional total gastrectomy accompanying pancreatosplenectomy and that of subtotal gastrectomy with lymph node dissection of the conventional style preserving the spleen and the pancreas. In our study Appleby's operation was performed in 65 cases and the conventional procedures were in 41 cases and 50 cases, respectively. Both groups have almost identical prognostic backgrounds except for the lymph node status. The overall 5-year survival rate of Appleby's procedure group was higher (49.5%) than that of the conventional procedure group (23%) in spite of higher percentage of positive rate of the 2nd group of lymph node(n2+) in Appleby's procedure group. Furthermore, in the cases with serosal invasion(se) and positive metastasis in the 1st group of lymph node (n1+), the 5 year survival rate of Appleby's procedure group was higher (64%) than that of the conventional procedure group (32%), and the difference was statistically significant (p less than 0.01). On the other hand, no difference was observed in the 5-year survival rate between both groups in which the serosae were invaded and the 2nd group of lymph nodes were involved. Our study shows that Appleby's procedure salvaged further 32% of patients that would have been lost if they had undergone the conventional procedure. PMID- 2586415 TI - [Radical operation for carcinoma of gastric cardia--lymph node dissection by laparosternophrenotomy approach]. AB - The adequate esophago-gastric resection and lymph node dissection can be performed without the necessity of a thoracotomy, by using the laparosternophrenotomy approach. For tumors restricted to lower esophagus of 4cm in localized tumors or 3cm in invaded tumors above the EG junction, the sternotomy approach is utilized. However, if the tumor extends to more than the above criteria, the thoracoabdominal approach must be utilized. For 14 years, 85 cases with tumor of gastric cardia were performed by sternotomy approach and 76 cases were performed by thoracotomy approach. The lymph node metastatic rate in the lower thoracic cavity was 26% in total. The lymph node metastatic rate of No. 110 was 22.6%, No. 111 was 17.4% and No. 112 was 12.5%. These results show the lymph node dissection in the lower thoracic cavity is very important in tumors of gastric cardia. The five year survival rate was 41% in patients who undergone curative operation by the sternotomy approach, and 45% in patients performed by the thoracotomy approach. According to our study of the lymph fluid stream in gastric cardia tumors using carbon, the lymph node dissection around the renal vein is important. This approach has less respiratory disturbance than the thoracotomy. This procedure is one of the best approaches for carcinoma of gastric cardia according to our criteria. PMID- 2586417 TI - [Current state of the treatment of congenital biliary atresia]. AB - Current state of the treatment of biliary atresia was studied concerning following factors based on our experience of 240 patients during 1966 to 1988, particularly 103 patients who received Kasai operation with Suruga II modification. 1. Operative results: Overall and Suruga II. 2. Predictable factors of the prognosis at the first radical operation, especially, among the age, the hepatic fibrosis and the size of ductuli at porta hepatis. 3. Technical refinement of Kasai operation, especially concerning the exposure of portal area and the anastomosis. 4. Our recent device of modified Kasai operation, that is, hepatic portoduodenostomy with interposition of ileocecoappendix. 5. Rehepatic portoenterostomy in case of poor postoperative bile flow. From our experiences, Kasai operation is indicated to the patients who have mild or moderate liver fibrosis and good sized ductuli at porta hepatis, but not to the patients who have advanced liver fibrosis and extremely poor ductuli. In such circumstance, liver transplantation should be considered. Rehepatic portoenterostomy is only indicated to the patients who have a good bile flow after the initial Kasai operation but not to the patients who have no bile flow. PMID- 2586419 TI - [Early complications after hepatic porto-jejunostomy in biliary atresia]. AB - Postoperative complications which developed within three years after hepatic porto-jejunostomy (Kasai's operation) in 126 patients of biliary atresia were analyzed. Ascending cholangitis developed in 47 of 97 bile excreted patients. The excretion of bile ceased in another 18 patients without any symptom of cholangitis. Adhesive ileus, bleeding from the porta hepatis, wound dehiscence, and anastomotic leak developed less frequently. The mortality rate of the patients with these complications, especially with cholangitis or with cessation of the bile excretion, was extremely high; twenty nine (62%) out of 47 patients with cholangitis, and 14(78%) out of 18 patients with cessation of the bile excretion died. On the other hand, the mortality rate in 24 patients with bile excretion but without any postoperative complication was only 8% (2 patients). An intussusception type antireflux valve in the Roux-en-Y loop was effective for preventing cholangitis; cholangitis developed in none of 8 patients with an anti reflux valve, whereas cholangitis developed in 25(48%) of recent 52 patients without a valve. PMID- 2586418 TI - [Late complications after successful Kasai's operation for biliary atresia]. AB - The late complications in 25 patients more than 3 years after successful Kasai's operation for biliary atresia were presented. Nine (36%) of these 25 patients had episodes of variceal hemorrhage with portal hypertension, and biliary reobstruction in 3 (12%), bleeding from duodenal ulcer in 2, bleeding from gastric erosion in one, and diffuse pulmonary arterio-venous shunt in one were observed. Recently esophageal varices have been well controlled by endoscopic sclerotherapy, and the surgical treatment may be indicated in older children complicated with severe hypersplenism and marked splenomegaly, which are resistant for sclerotherapy. As a surgical procedure, splenectomy with periesophago-gastric devascularization (Hassab's operation) seems to be very useful for portal hypertension by biliary cirrhosis. The reoperation, hepaticoenterostomy, was performed in 3 patients with biliary reobstruction. All three patients are alive and well, and two of them are at 19 years (university student) and 24 years (married life) of age. Hepatic Rehepaticoenterostomy is well indicated rather than liver transplantation, if biliary reobstruction is incurable with conservative therapy. Many of the patients with complications were able to carry on an almost normal life, if suitable treatments for complications were taken. PMID- 2586420 TI - [Liver transplantation for biliary atresia with special reference to the Japanese children who received liver transplantation in foreign countries]. AB - Seven cases out of 8 Japanese children who received orthotopic liver transplantation (OLT) in foreign countries because of biliary atresia as of Oct 1988 are reported. Their clinical courses after OLT have been good. Despite being satisfied with the results, their parents and family feel anxiety such as long term postoperative care and side effects of immunosuppressive therapy. Cost and the handling of rejection or retransplantation were pointed out as the greatest problems related to receiving OLT in foreign countries. PMID- 2586421 TI - [Inhibition of thromboxane production might ameliorate liver blood flow in shock]. AB - We investigated whether thromboxane (TX), a vasoconstrictor, contributes to liver disturbance in shock by reducing liver blood flow. SUBJECTS AND METHODS: experimental groups: Sham, Et: endotoxin 4mg/kg, BDL + Et: bile duct ligation with Et, OKY. BDL + BDL + Et with infusion of OKYO46 (TX synthetase inhibitor) 5mg, HT: three days after 70% hepatectomy, OKY. HT: HT receiving OKYO46. We evaluated prostanoid and morbidity in hepatectomized cases. MEASUREMENT: TX, liver phospholipid, liver blood flow, endotoxin. RESULTS: Higher TX levels in blood and liver, and reduced liver phospholipid and liver blood flow in BDL + Et returned close to sham by OKYO46. High blood endotoxin in HT decreased by OKYO46. Intraoperative blood losses in cases with postoperative intraabdominal infection or hepatic failure were greater than those without complication. Hepatectomized cases with intraabdominal infection showed higher blood TX than those without complication. TX might be associated with decreased liver blood flow and with postoperative complication during shock. To reduce TX production would be beneficial in shock by ameliorating liver blood flow. PMID- 2586416 TI - [The present status and problems in the treatment of biliary atresia with special reference to surgical and long-term results]. AB - The surgical results are not satisfactory yet in Japan and only 46% of the patients are free of jaundice 3 years ago. However, we found many presentations which reported jaundice disappearance rate with more than 80% in the last several years. The main cause of death in jaundiced patients with the failed hepatic portoenterostomy was hepatic failure. Other causes of deaths in these patients, including those died within one month after operation, were peritonitis, cardiac and/or renal failure, hemorrhagic tendency and lung edema. The main cause of death in jaundice-free patients was rupture of the esophageal varices. We examined 48 long-term survivors ranging in age from 10 to 33 years. There were 41 cases without and 7 with jaundice. Thirty-seven (77%) of 48 cases were leading their normal lives. Among them, 6 cases were enjoying their lives after overcoming the sequelae, such as portal hypertension. The morbidities of the remaining 11 (23%) long-term survivors were jaundice in 7, portal hypertension in 5, encephalopathy after splenorenal shunt in 1 and so on. The cured states of most cases without jaundice are satisfactory and eventually these former patients can achieve a favorable quality of life. PMID- 2586422 TI - [The role of oxygen free radical and free radical scavenger in septic and hemorrhagic shock]. AB - The roles of oxygen free radical (O2-), lipoperoxide (LPO) and free radical scavenger were clinically and experimentally studied in septic and hemorrhagic shock. The reduction of hepatic tissue blood flow (TBF) were equalized in two groups (40-55% of normal level) and rats were subdivided into 3 groups: untreated, normal saline (NS) continuous IV and superoxide dismutase: SOD + catalase (S/c) continuous IV as free radical scavenger. The change of TBF, destruction of mitochondrial structure and elevation of LPO were prevented by S/c in Et shock. No significant effect by S/c was observed in hemorrhagic shock. The neutrophil derived O2- was markedly elevated in Et shock animals as well as septic shock patients but no significant change was noted in hemorrhagic shock animals or non septic shock patient. SOD and catalase were effective for neutrophil derived O2- in septic shock whereas little beneficial effect was noted in hemorrhagic or non septic shock. PMID- 2586423 TI - [Effects of anti-toxic agents in septic shock]. AB - From 1975 to 1987, we had 56 patients of septic shock in the Department of Surgery. Multiple organ failure occurred in many septic patients. Glucocorticoids inhibited the secretion of chemical mediators (histamine, serotonin and bradykinin) and then prevented septic shock. Intravenous administration of dexamethasone showed no change in amounts of leukotrienes (LTC4, LTD4, LTE4) in venous blood in peritonitis rats. Dexamethasone treatment of septic rats corrected FDP and nearly normalized PEP values. When glucocorticoid was given intravenously at the time of cecal incision, PFKase, PKase, G6Pase and PEPCK were stimulated, respectively. Protease inhibitor FUT-175 was infused in 5% dextrose (0.1mg/ml/hr) in septic rats. Survival time was 12.1 +/- 2.3 hour in FUT-175 group and 6.6 +/- 1.1 hr without FUT-175. In FUT-175 injected rats G6P decreased by 20%, FDP increased 50% and lactate doubled. PEP levels increased 30% above peritonitis values. The amounts of leukotrienes (LTC4, LTD4, LTE4) in venous blood were gradually decreased by pretreatment with the specific 5-lipoxygenase inhibitor AA-861 after peritonitis. Specific treatments in septic shock should be instituted administration of glucocorticoid, antibiotics, protease inhibitor and lipoxygenase inhibitor. The importance of septic shock as a factor contributing to organ failure must be acknowledge. We believe that the prompt and efficacious treatment of septic shock is the best therapy. PMID- 2586424 TI - [Cellular metabolic consideration in the pathophysiology and the treatment of shock]. AB - Shock is defined as the summation of cellular dysfunction and resultant impairment of the function in various organs. The typical such condition can be observed in shock-induced multiple organ failure (MOF). Therefore, the most effective and fundamental management against shock should be the improvement of such cellular dysfunction. The present study was undertaken to investigate the cellular metabolic abnormalities and their treatment in shock-induced MOF patients. The severity of cellular damage was evaluated with cellular injury score (CIS), which can be calculated by scoring the values of osmolality gap, arterial ketone body ratio and blood lactate. The CIS correlated significantly with the outcome and the number of failing organs in the MOF patients. Since tissue hypoxia and humoral mediator have been considered to play a key role in the development of such cellular dysfunction, protease inhibitor was administered to such patients and oxygen metabolism was improved with catecholamine. The CIS improved among survived MOF patients following those treatments. These results suggest that the shock-induced MOF is the summation of the cellular dysfunction which can be assessed with the CIS, and that such cellular dysfunction could be improved through the therapeutic approach to the humoral mediators and/or tissue oxygen metabolism. PMID- 2586425 TI - [Result of surgical treatment to benign thyroid tumor]. AB - Surgical results of 81 cases with various benign thyroid tumors were reviewed. All had undergone mainly hemi-lobectomy including isthmectomy and had been followed up for more than 2 years. Sixty-eight (84%) have been well without any complaint. However, 5 of 15 cases with adenomatous goiter (AG) again developed nodule(s) in the remnant thyroid and 1 of 37 cases with adenoma developed cancer in the remnant. In order to prevent recurrence in the cases with AG, total thyroidectomy may be required with the meticulous selection of the case. For the cases with AG which undergone hemilobectomy or lumpectomy, TSH suppression treatment may be also required after surgery. It is of caution that the nodule developed in the thyroid after surgery may be not always the same nodule as primary one. PMID- 2586426 TI - [Therapeutic strategy for adenomatous goiter from the viewpoint of postoperative outcome and epidermal growth factor receptor study]. AB - Adenomatous goiter (AG) is regarded as a benign tumor-like lesion. In the present study, both the postoperative outcome and the localization of epidermal growth factor receptor (EGF-R) were investigated to determine proper therapeutic modalities for AG. In this series, 377 surgical patients were studied. Immunohistochemical observation was carried out according to the ABC procedure. Results were as follows: 1) among the all 377 patients, primary cases were 343 and the remainder, 34 cases (9%), recurrent, 2) majority of the 34 recurrent patients showed multinodular goiter type occupying one whole lobe or both sides. Initial surgical strategy for these cases was only enucleation of the all nodules confirmed macroscopically, 3) coexistence of cancer in AG was observed in 18 cases (5%). Seventeen out of them were latent carcinomas found in the multinodular goiter, and 4) those multinodular patients associated with latent carcinoma revealed presence of EGF-R not only in the malignant lesions but also in the hyperplastic parts. These observations suggest that surgical treatment should be considered for multinodular AG patients. In addition, near-total lobectomy of the diseased side might be recommended as an operative procedure because of the prevention of postoperative recurrence and complications. PMID- 2586427 TI - [Study on follow-up of patients with biopsy-proven breast disease]. AB - Eight hundred forty-one patients with biopsy-proven benign breast disease were followed annually in prospective manner for 1-10 years to analyse breast cancer development at aspect of histologic features, age at entry and mammographic patterns by Wolfe. No association was found between patients who developed cancer and those who did not with respect to the initial histologic features. The rate of breast cancer development in patients in thirties was the highest. The breast cancer development was found most often in less than three years follow-up period. The breast parenchymal patterns at entry related to cancer development. In 10 cancer patients, 8 patients showed DY pattern and 2 showed P2 patterns. The present results demonstrate that the patients with biopsy-proven benign breast disease in thirties, in less than 3 years follow up period and have parenchymal patterns of P2 or DY should be followed carefully. PMID- 2586428 TI - [Follow-up study of benign breast diseases]. AB - Follow-up study after surgery of the benign breast disease revealed that rates of the recurrence were 50%, 6%, 4%, 3.5% in those who had phyllodes tumor, duct ectasia, intraductal papillary lesion, and multiple fibroadenoma, respectively. Incidences of the subsequent breast cancer development were 14.3% after ADH, 11.7% after ALH, 1.5% after PDWA, respectively. However no difference was found statistically among those diseases(X2 = 2.89). The longest interval between time of the first surgery and time of detection of subsequently developing cancer was 68 months. Accordingly, checks at three times of postoperative third, fifth and eighth year were required for early detection of such subsequent breast cancer, using image diagnostic methods. PMID- 2586429 TI - [Role and significance of extended operation in the treatment of stage IV carcinoma of the esophagus]. AB - A total of 106 cases of esophageal cancers treated in our hospital between Jan. 1980 and Jan. 1989 were studied to evaluate the role and significance of extended surgical resection in the treatment of the stage IV patients with T3 tumors. Of those treated were included six patients of stage 0, four of stage II, twenty nine of stage III, and fifty-two of stage IV. Resectability rate was 82.1%, direct death rate was 8.0%. An overall one-year and three-year survival rate were 54.0% and 21.8%, and those of stage IV were 26.6% and 6.4% respectively. For thirty-one of the 52 patients with T3 tumor, combined radical resection of the structures were performed, with a mortality rate of 12.9%, and a mean survival period of 720.2 days for n0, 239.5 days for n2 (+) and 299.4 days for n3-4 (+). Mean survival of the patients without combined resection of the involved structures were 465 days(n0), 156 days(n2) and 236 days(n3-4) respectively. The organs resected included the trachea(17), thoracic aorta(7), carotid artery(4), pericardium(4), lung(3) and so on. It is concluded that improved survival for even advanced T3 carcinomas especially without lymph nodes metastasis might be obtained by the combined radical resection of the involved neighboring structures. PMID- 2586430 TI - [Evaluation of the extended operation in stage 4 esophageal cancer]. AB - For the last four years, 174 cases of thoracic esophageal cancer have been resected in our department. Stage 4 cancer cases were encountered in 73 cases (42%) of total resected cancer cases. As the location of lesion, 1m was most frequent in 52%, followed by Ei in 23%. The 2-year and 3-year survival rate were 25% and 17% respectively. Analyzing 73 cases of stage 4 cancer, a0-2n3,4 was found in 52 cases (71%), a3n0-2 12(16%), a3n3,4 7(10%) and M1 2(3%). Invasion to the trachea and bronchi was seen in 11 and that to the aorta was in 7. As for surgical procedures, the combined resection of the aorta was performed in two cases. The postoperative course was smooth, however, the prolonged survival was not obtained due to the recurrence of cancer. The lymph node metastasis was widely observed in the cervical region, mediastinum and abdominal cavity. The thoracic paratracheal lymph node metastasis was the most frequent. The lymph node dissection was necessary in these three regions. Especially the sufficient dissection in the upper mediastinal lymph nodes, that is, the right recurrent nerve nodes, the left recurrent nodes and the infraaortic arch nodes, was very important. PMID- 2586431 TI - [Significance of extended radical surgery for stage IV gastric cancer]. AB - Forty percent of patients with gastric cancer with direct infiltration to adjacent organs survived for more than 5 years after curative resection. Favorable results were obtained in cases in which combined resection of the body of the pancreas or the liver was performed due to cancer infiltration. However, patients who had undergone gastrectomy with combined colectomy or pancreatoduodenectomy showed a poor survival rate. The postoperative 5-year survival rate was 29% for patients who had presented with group 3 lymph node metastasis and undergone potentially curative surgery. Particularly, favorable results were obtained in cases with metastases confined to lymph nodes in the hepatoduodenal ligament. In dissection of the deepest nodes, lymph nodes in the hepatoduodenal ligament is the most important to remove in surgery for stage IV gastric cancer. We have performed gastrectomy combined with dissection of group 1 and 2 lymph nodes in the treatment of patients with gastric cancer with peritoneal metastasis. Results obtained so far revealed that only patients with a lesser extent of serosal invasion survived longer after operation. We are presently conducting a trial of hyperthermia combined with anticancer chemotherapy as a possible method for prolongation of survival of patients with peritoneal metastasis of gastric cancer. PMID- 2586432 TI - [Significance of extended radical operation for advanced gastric cancer of stage IV]. AB - The significance of extended radical operation (gastric resection with R3 and paraaortic lymph-node mean value of R4 dissection) was retrospectively studied in 1,363 cases (1968-1987) of advanced gastric cancer in Stage IV. For liver metastasis, gastric and R2 lymph node resection with transcatheter arterial embolization or chemoembolization was superior to liver resection. The operative results showed that 5-year survival rate of radical dissection of RO-2 was 19.3% and that of R3-4 was 34.6% (p less than 0.05). It also suggested that the operation was effective in 78% of patients with POHO and POHO, ow(-) and aw(-). As a conclusion, extended radical operation is significant as the treatment of advanced gastric cancer in Stage IV. PMID- 2586433 TI - [Extended surgery for advanced colo-rectal carcinoma (stage IV and V)]. AB - Two hundred fifty-five patients with colo-rectal carcinoma underwent operations in our department between January 1980 and December 1988. The five-year survival rate of stage IV patients (30 cases) was 58%, and the three-year survival rate of stage V patients (44 cases) was 8%. The study for the expression of blood group related cancer-associated antigens (Lea, CA19-9, etc.) in colo-rectal cancers using immunohistological method and a series of mouse monoclonal antibodies revealed that the stromal staining pattern of CA19-9 means high malignancy with poor prognosis. Nineteen patients with locally invading rectal cancer were submitted to total pelvic exenteration with urinary diversion. The operative mortality rate was 5.3%. A determinate 5-year survival rate of 4.5 was achieved. Fourteen patients with local recurrent lesions of rectal cancer following abdominoperineal resection were submitted to pelvic exenteration combined with sacral resection. Two patients are alive disease free for longer than four years at this writing. This operation assures a better quality of life, lessening of symptoms, disease control and, in selected patients, a cure. PMID- 2586434 TI - [Immunotherapy for lung cancer by streptococcal preparation OK-432]. AB - To evaluate the clinical efficacy of OK-432 immunotherapy, patients admitted between 1975 and 1982 were randomized into two groups: An immunochemotherapy (IM C) group and a chemotherapy (control) group. For each group, a fixed chemotherapy was administered using a combination of three drugs. The survival rates of cases with non-small cell carcinoma were evaluated at the end of 1987. One hundred and fifty-seven cases in the IM-C group and 148 in the control group were eligible for evaluation of long-term survival rates. Statistically significant improvement of the survival rates in the IM-G group were noted in the following items: All cases, resected cases, non-resected cases, resected stage I + II cases, resected stage III cases, completely resected cases, incompletely resected cases, and cases with epidermoid carcinoma. However, in comparison of adenocarcinoma there was no significant difference between the two groups. SU-polysaccharide skin test and natural killer activity were the best immunological parameters during the OK 432 therapy. To intensify the effects of immunotherapy, a possibility of regional immunotherapy was studied following some experimental works. Regional infusion of LAK cells (induced by incubation of patient's lymphocytes with rIL-2) through bronchial artery after regional infusion of OK-432 and chemotherapeutics showed favorable effect for advanced lung cancer. Future prospect of these regional adoptive immunotherapy was discussed. PMID- 2586435 TI - [Immunity of gut-associated lymphoid tissue and the role of the oral immunotherapy in multi-disciplinary treatment of the digestive organ cancer]. AB - In order to augment antitumor immunity of gut-associated lymphoid tissue in digestive organ cancer, oral administration of various biological response modifiers were studied using mice transplanted with cecal tumor. Among them OK 432 was the most effective and clinical application of oral OK-432 was studied. Autoradiogram and immunofluorescence studies showed the absorption of orally administered OK-432 from the gut. In phase I study oral OK-432 was much less toxic than other administration routes. Phase II study showed that oral OK-432 at various doses augmented antitumor immunity of the lymphocytes of peripheral blood and regional lymph node. In a multi-institutional study on postoperative adjuvant immunotherapy, 1011 gastric cancer patients were accumulated and randomized to compare the effects of oral and intradermal OK-432. In patients who underwent curative operation, 1-, 2- and 3-year survival rates (%) were 95, 88 and 82 for oral OK-432 group (n = 255), 88, 83 and 80 for the placebo group (n = 260), and 89, 79 and 73 for intradermal OK-432 group (n = 261). There was significant differences among cumulative survivals of three groups, and this life-prolonging effect of oral OK-432 was remarkable for stage II or III patients. These results demonstrate that oral immunotherapy with OK-432 is useful as an immunotherapy of digestive organ cancers. PMID- 2586436 TI - [The effect of endoscopical intratumoral injection of OK-432 in gastric carcinoma]. AB - Many BRMs (biological response modifiers) have been used for post-operative immunochemotherapy. And their usefulness were also reported. Nevertheless it is still unknown that which route, how much doses and which timing are the most effective to administer these drugs. We used BRMs intratumorally and preoperatively. To reconfirm the efficacy of intratumoral injection therapy randomized study was performed in gastric carcinoma. Three hundred and ninety five cases were entered, 199 cases in group A which were treated preoperatively with OK-432 intratumorally and 196 cases in group B which were control, respectively. In the cases which had marked infiltration of lymphoid cells in tumor sites, the two year survival rate of group A was significantly better than that of group B (p less than 0.05). On the study of recurrent forms, the distal lymph node metastasis was markedly decreased in group A. The ratio of metastasis to the distal lymph nodes in group A was 5-10% lesser than that in group B on the each depth of tumor invasion. The ratio of lymph nodes metastasis was almost similar in the each group, but the number of metastatic lymph nodes was significantly reduced in high grade tumor infiltrated cases in group A (p less than 0.005). These results suggest that preoperative endoscopically intratumoral administration of OK-432 suppresses the lymph node metastasis and improves the postoperative survival rate. PMID- 2586437 TI - [Clinical effects of PSK on esophageal and gastric cancer patients and usefulness of serum levels of glycoproteins and HLA antigens as prognostic indicators]. AB - This study was carried out to evaluate whether the preoperative levels of serum glycoproteins (CEA, SCC, TPA, IAP, ACT, ASP and sialic acid) and HLA antigens (class I and II) could be potential aids in the selection of suitable gastric and esophageal cancer patients for postoperative adjuvant immunotherapy of PSK. Gastric cancer patients underwent gastrectomy and received postoperative adjuvant chemotherapy (MMC, FT and ADR) with or without PSK. One hundred and forty esophageal cancer patients in cooperative study groups (organizing chairman; Dr. Hiroshi Satoh) underwent esophagectomy and received postoperative adjuvant radiotherapy and chemotherapy (FT, BLM) with or without PSK. The efficacy of PSK was recognized in the patients with normal levels of all glycoproteins in gastric cancer, and with normal levels of CEA or SCC or TPA and abnormal levels of one or more APRs in both gastric and esophageal cancer, and with positive HLA-B40 antigen. The combination of tumor-associated factors, such as CEA, SCC and TPA and various non-specific reactants such as APRs was useful as a prognostic indicator. In addition, some of HLA antigens were also valuable. The pretreatment levels of glycoproteins and HLA antigens have potential aids in the selection of patients with gastric and esophageal cancer for PSK treatment. PMID- 2586438 TI - [Clinical efficacy of LAK cell adoptive immunotherapy in advanced cancer patients]. AB - Clinical efficacy of lymphokine-activated killer (LAK) cell adoptive immunotherapy (AIT) in combination with plasma exchange was investigated as protocol 1 in 24 patients with advanced cancer. For the development of protocol 1, AIT in combination with plasma exchange, OK-432, interleukin-2 (IL-2) and cyclophosphamide was performed as protocol 2, in which LAK cells, OK-432 and IL-2 were administered through the catheter located in the hepatic or bronchial artery. The clinical efficacy of protocol 1 was found in patients with pleural effusion and metastasis to the lung or liver and resulted in 4 partial responses (20%) and 1 minor response of 20 evaluable cases. On the other hand, that of protocol 2 did 1 partial response (20%) in 5 cases. In vitro cytotoxic activity against either Daudi or K 562 tumor cells of peripheral blood lymphocytes from patient given intraaorta administration of OK-432 and IL-2 was tended to increase to be higher than that from nontreated patients. Postoperative immunodepression in esophageal cancer was blocked by AIT, suggesting the usefulness of AIT as a postoperative adjuvant immunotherapy. Thus, target organ of AIT should be limited for better therapeutic effect and the superiority of local AIT in combination with biological response modifiers may be indicated. PMID- 2586439 TI - [Adoptive immunotherapy with LAK cell and IL-2 against primary lung cancer]. AB - Adoptive immunotherapy using LAK cells and IL-2 was performed against stage III and IV primary lung cancer patients after surgery. A randomized controlled study consisting of control group A, chemotherapy (CDDP + VDS) group B and chemo immunotherapy (CDDP+VDS, IL2+LAK cells) group C suggested better survival rate in the group C. Direct effects were studied against 8 recurrent or inoperable lung cancer cases. Complete response was obtained against a pleuritis and pericarditis carcinomatosa case when in vitro stimulated LAK cells (St-LAK) were administered locally. Partial response was observed against a inoperable case when LAK-BAI (bronchial arterial infusion) was combined with radiation therapy. PMID- 2586440 TI - [Implications of preoperative angiography and coronary artery bypass grafting for patients with combined coronary artery and great vessels diseases]. AB - Preoperative coronary angiography showed that the significant coronary artery disease (CAD) was present in 47% of patients with thoracic aortic aneurysm (TAA), abdominal aortic aneurysm (AAA), or aortoiliac occlusive disease (A.I). Fifty seven patients underwent the both coronary artery and great vessel diseases on the simultaneous or sequential stage. As CAD, 13 patients had one vessel disease (VD), 18 had two-VD, 26 had three-VD and 4 of them had left main trunk lesions. As great vessel diseases, 23 patients had A-I, 20 had AAA, 8 had TAA, 5 had TAA+AAA, and 1 had TAA+A-I. There were 4 early deaths (7%) in 57 patients, and 4 (3%) in total 120 coronary and great vessel's operative procedures. The 5-year survival rates were 57.4 +/- 15.5% for TAA, 87.1 +/- 8.5% for AAA and 63.9 +/- 11.1% for A-I, which were not significantly different from those of patients without CAD, respectively except for TAA. The present data suggest that preoperative coronary angiography and CABG in the selected patients may have the beneficial effects on survival and quality of life. PMID- 2586441 TI - [Indication for coronary revascularization in aortic surgery]. AB - In order to know how to treat the coronary artery disease in scheduled aortic surgery for aortic aneurysms, a prospective study started about ten years ago using routine coronary angiography (CAG). Thoracic aortic aneurysm (TAA): CAG was performed in 73 among 143 patients and 18 had significant coronary artery stenoses (CAD), 3 of whom had angina. Concomitant CABG was performed in 2 of 4 patients requiring coronary revascularization (CR) to prevent intraoperative myocardial ischemia. Complications due to CAD were experienced in the 2 patients without CR despite of angina, while patients without angina or with CR had no complication. Abdominal aortic aneurysm (AAA): Seventy six among 150 patients had CAG, and CAD was found in 38. CR was indicated to 5 of 7 patients with angina. Complications occurred in 2 patients who had not CR in spite of angina. Patients without angina had no complication. CONCLUSION: 1) Patients who had angina are at high risk for complications due to CAD. 2) Patients with angina and necessity of cardiac arrest during aneurysmectomy should have coronary revascularization prior to aneurysmectomy. 3) Patients without angina are at low risk for myocardial ischemia in the perioperative period of aortic surgery. PMID- 2586442 TI - [Influence of ischemic heart disease on early and late mortality after aortic reconstruction for abdominal aortic aneurysm and aortoiliac occlusive disease]. AB - A retrospective study was undertaken to assess the influence of ischemic heart disease (IHD) on the early and late mortality of patients undergoing elective repair of an abdominal aortic aneurysms (AAA) or aortoiliac occlusive disease (AIOD). The patients were divided into IHD and non-IHD groups on routine clinical grounds. Among 157 patients with AAA, postoperative myocardial infarction occurred in 12.8% of the IHD group compared with 0.9% of the non-IHD group (P less than 0.05). The late mortality rate in the IHD group was higher than in the non-IHD group (p less than 0.05), and the mortality rate from myocardial infarction was 30% in the IHD group compared with 13% in the non-IHD group. Among 119 patients with AIOD, clinical evidence of IHD was found in 24 patients and extra-anatomical bypass was performed in 54% of these patients, compared with 35% of the patients in the non-IHD group. There was no occurrence of postoperative myocardial infarction. This study shows that an aggressive diagnostic approach should be taken for patients with AAA who have clinical evidence of IHD and that reevaluation of IHD should be performed in patients with AIOD after aortic reconstructive surgery. PMID- 2586443 TI - [Surgical treatment for aortic diseases associated with coronary artery stenosis]. AB - Three hundred and one patients undergoing aortic surgery (247 aneurysm cases and 54 arteriosclerotic obstruction cases) were evaluated in respect to the treatment for the associated coronary artery stenosis. Twenty-four among total cases (8%) showed the presence of coronary artery stenosis; 16 cases among aneurysm cases (6.5%) and 8 cases among arteriosclerotic obstruction cases (14.8%). Coronary revascularization was performed in 10 cases and the early operate death was observed in one case. Two abdominal aneurysm cases and 4 arteriosclerotic obstruction cases received two-staged aortic and coronary operation, since either aortic or coronary lesion was considered lethal. However, 3 cases of dissecting aneurysm (type I or II), and case of arteriosclerotic obstruction case having left ventricular aneurysm received simultaneous aortic and coronary surgery, since both of the lesions were highly lethal. These data are consistent with the conclusion that the combined aortic and coronary lesion should be treated with the two-staged operation, and that the simultaneous aortic and coronary surgery should be performed only when the both lesions are lethal. PMID- 2586445 TI - [Surgery of aortic disease with coronary heart disease]. AB - From 1978 through 1989, 1200 patients underwent attempted coronary surgery. Seventy-six CABG-patients were recognized aorto-vascular disease. Thirty-one CABG patients were operated with vascular surgery. Operative mortality of CABG was 0% (0/76). Operative mortality of vascular surgery was 3.2% (1/31). Total operative mortality was 1.1% (1/91). PMID- 2586444 TI - [Surgery for aortic aneurysms with coronary disease]. AB - Between 1981 and 1988, 52 patients with dissecting aneurysms were operated and four of them (7.7%) had right coronary dissections that were repaired by Bentall's method with or without right coronary bypass grafting (CABG). Three (8.5%) of 35 patients with thoracic aneurysms had coronary disease. Among them, two had one vessel disease (1VD) and one had 2VD; two underwent temporary axillofemoral bypass grafting (AFBG) without CABG and one underwent extracorporeal circulation with CABG. Eight (5.6%) of 142 patients with abdominal aneurysms had coronary disease. They consisted of three patients with 1VD, two with 2VD and three with 3VD; their ejection fraction rates were 0.46 to 0.75. Three of them underwent temporary AFBG and one first underwent CABG but later underwent abdominal aortic graft replacement. In conclusion, patients with good coronary distal run-off and a low ejection fraction rate (under 0.5) should initially undergo CABG, but for those with poor run-off, temporary AFBG is better to prevent cardiac afterload. PMID- 2586447 TI - [Undergraduate medical education]. PMID- 2586446 TI - [For Japanese surgery in the 21st century]. PMID- 2586448 TI - [Surgical training in early postgraduate education]. PMID- 2586449 TI - [Training of surgeons and the system of medical specialists]. PMID- 2586450 TI - [Future of the surgical department]. PMID- 2586451 TI - [Internationalization and the surgical specialty]. PMID- 2586452 TI - [Surgical treatment and medical ethics]. PMID- 2586453 TI - [Revolution in medical technology and the future of the surgical specialty]. PMID- 2586454 TI - [Continuing surgical education and the aging society]. PMID- 2586455 TI - [St. Jude Medical valve replacement: clinical experience with 1,039 patients]. AB - St. Jude Medical valve replacement was performed in 1,039 patients; 320 had aortic (AVR), 543 mitral (MVR), and 176 had double valve replacement (DVR). There were 44(4.2%) early deaths. Follow-up extended in 995 patients from 10 to 130 months, with a cumulative period of 2,730 patients-years. The overall survival rates of AVR, MVR, and DVR patients at 10 years were 60.5%, 89.6%, 90.3% respectively. The linearized incidences of valve thrombosis, thromboembolism, anticoagulation-related hemorrhage, prosthetic valve endocarditis, and significant hemolysis were as follows: 0.11%/pt-yr, 1.33%/pt-yr, 0.04%/pt-yr, 0.18%/pt-yr, and 0.11%/pt-yr, respectively. There were no structural failure after 10 years follow-up. Reoperation (explant and re-replacement or suture repair) was required in 10 patients. Seven of them had periprosthetic leakage, 2 had valve thrombosis, and one underwent reoperation because of a technical error. Actuarially over 98% of patients were free of valve-related mortality at 10 years. St. Jude Medical valve is an excellent alternative for use in the surgical treatment of valvular heart disease. PMID- 2586456 TI - [Selection of valve prosthesis, reoperation and late result--surgical technique of reoperation with Bjork-Shiley prosthesis]. AB - Late result of Bjork-Shiley prosthesis selected in the aortic and mitral position for valve replacement was reviewed on 222 cases in our 10 years clinical experience. Late survival was 93.8% (5 yrs), 83% (10 yrs) in the aortic position, 94% (5 yrs) and 80% (10 yrs) in the mitral position. Valve-related complication by Bjork-Shiley prosthesis was very low in incidence as compared with that published by other institution with respects to thromboembolism, prosthetic valve endocarditis, reoperation, anticoagulation-related bleeding. Inflammatory aortic valve disease which developed valve detachment in the aortic position with Bjork Shiley valve was treated with double-suture technique in the aortic annulus and fixation of the graft with the inside of sinus of Valsalva, en-bloc reconstruction with composite graft using Bjork-Shiley valve inside of the sinus Valsalva without touch to coronary ostium. The other surgical procedure was translocation method using Bjork-Shiley prosthesis. Our clinical results suggest that Bjork-Shiley prosthesis is still recommended in the aortic and mitral positions from low incidence of valve-related complication and good late survival. PMID- 2586457 TI - [An eighteen-year evaluation of the Bjork-Shiley valve prosthesis]. AB - We evaluated the long-term (18 years) results of 356 patients undergoing valve replacement with Bjork-Shiley valve prosthesis (aortic, 212; mitral 120; double valve, 24) between 1970 and 1988. Actuarial survival rates were 90% (18 years) for AVR, 80% 'years) for MVR and 90% (8 years) for DVR. Actuarial rates of thromboembolism were 99% (18 years) for AVR, 98% (8 years) for MVR and 94% (8 years) for DVR. Actuarial rates of freedom from events (including valve failure, thromboembolism, reoperation and prosthetic valve endocarditis) were 82% (18 years) for AVR, 95% (8 years) and 94% (8 years) for DVR. There were no differences in these results among spherical disc, convexo-concave disc and monostrut valve. In conclusion, this study demonstrated that Bjork-Shiley valve showed a low incidence of postoperative events. These results endorse our choice of the Bjork-Shiley. PMID- 2586458 TI - [The clinical criteria for Carpentier-Edwards bioprosthesis in the mitral position]. AB - This is a comparative study of late results of mitral valve replacement between Carpentier-Edwards (C-E) and Bjork-Shiley (B-S) valve prosthesis. The purpose of this study is to clarify the clinical criteria for C-E valve. C-E valve was implanted in 202 patients. The mean follow up period was 5.8 years and the longest one was 11 years. For B-S valve, it was 132 patients, 5.3 years and 17 years, respectively. With respect to the incidence of thromboembolic episodes, in spite of no anticoagulant therapy in the C-E group, there was no statistical difference between the C-E and the B-S groups. The incidence of valve related complication in the C-E group was significantly lower than that in the B-S group 5 years postoperatively. But that in the B-S group was significantly low 10 years postoperatively. Since the over 60 years old patients in the C-E group had low incidence of primary tissue failure, over ten years durability might be secured. In conclusion, the present clinical criteria for C-E valve should be as follows: 1) the patient older than 65 years, 2) the patient with contraindication for anticoagulant therapy, 3) the woman who desires pregnancy and 4) the patient with hemorrhagic diathesis caused by cardiac cachexia, liver cirrhosis and so on. PMID- 2586460 TI - [Comparative analysis of long-term results with porcine-aortic, bovine pericardial and tilting disc valves]. AB - The three series with the first-generation valve prostheses were reviewed for long-term clinical evaluation in isolated aortic and mitral valve replacement. Hancock porcine xenograft was implanted in 71 patients from 1977 to 1979, ionescu Shiley pericardial xenograft (standard model) in 271 patients from 1979 to 1983, and Bjork-Shiley tilting disc valve in 194 from 1978 to 1986. In aortic position, no any significant difference among three valve types could be demonstrated in the actuarial survival and freedom from thromboembolism and valve infection, while the actuarial freedom from valve dysfunction in lonescu-Shiley valve was significantly lower than that in other two valves. Bjork-Shiley valve in mitral position showed satisfactory clinical performance in terms of valve-related complications and survival in comparison with two types of bioprosthetic valves. In our conclusion at present time, Bjork-Shiley valve is suitable for the first choice of both aortic and mitral valve prostheses. In case of valve replacement with a bioprosthesis, however, porcine aortic valve is a better choice for aortic, and bovine pericardial valve likely for mitral replacement. PMID- 2586459 TI - [Long-term results of mechanical valves in aortic position and biological valves in mitral and tricuspid positions]. AB - The long-term results of patients undergoing aortic valve replacement (AVR) with a mechanical valve (AM), mitral valve replacement with a biological valve (MB), and tricuspid valve replacement (TVR) with a biological valve (TB) operated upon from 1977 to 1988 were retrospectively analysed. A total of 899 patients received 1117 valves (381 AM, 633 TB, 103 TB) with a follow-up 3778 patient-years and 4582 valve-years. A significant incidence of thromboembolism, hemorrhage, and endocarditis was not found among AVR, MVR, TVR, or multiple valve replacement. We found a significantly decreased incidence of survival rate in multiple valve replacement compared with AVR or MVR, and a significantly increased incidence of reoperation in MB compared with AM and TB. We use AM and TB in any adult patients as a first choice. However, we prefer a mechanical valve in the mitral position except in patients over 65 years old, who have a short life expectancy, in whom anticoagulation is thought to be difficult, and who desire a biological valve. PMID- 2586461 TI - [Indications and results of non-shunting operations for esophageal varices]. AB - Non-shunting operations were performed in 522 patients with esophagogastric varices in our department from January 1964 to March 1989. Transthoracoabdominal esophageal transection was performed in 287 patients (devascularization of the distal esophagus and the proximal half of the stomach and transection of the esophagus). Transthoracic esophageal transection was performed in 125 patients (31 Walker's transection, 94 esophageal transection with devascularization of distal esophagus). Transabdominal esophageal transection was performed in 49 patients. Hassab's operation was performed in 49 patients and three patients were treated with other direct operations (proximal gastrectomy, etc.) Overall mortality of non-shunting operation was 5.0%. The five year survival of idiopathic portal hypertension was 77.6%, extrahepatic portal obstruction was 90.7% and liver cirrhosis was 63.1%. Five year survival of Child's grade A was 79.8%, Child's grade B was 72.9% and Child's grade C was 38.6%. Operation on Child's C patients should be avoided since the results in these patients have been unsatisfactory. Our overall results with esophageal transection over the last two decades are satisfactory. PMID- 2586462 TI - [Management of bleeding esophageal varices--efficacy of emergency embolization therapy]. AB - To increase durability for long term control of bleeding, additional treatment has to be performed. Since Oct. 1979, various embolizations that is percutaneous transhepatic obliteration (PTO), splenic artery embolization (SAE) and left gastric artery embolization (LGE) were introduced as conservative treatments, and have been used singly or concomitantly. Embolization has been employed in order to avoid the high risk of emergency operation. Complete hemostasis and prolonged efficacy could be obtained by introducing various embolizations. No emergency operation has been performed since all of these embolizations were introduced in Jan. 1983. The rates of hemostasis (100%), one month survival (90%), 1 year incidence of rebleeding (6.7%), 1 year survival (75.5%) and 3 year survival (62.5%) of emergency cases which received combined embolizations were better than the results of the cases which received emergency operation or endoscopic sclerotherapy alone. Moreover, the patients with gastric varices, including bleeding gastric varices treated with various combined embolizations, showed results of diminished varices in 78.9% of the patients. Thus to increase durability for long term control of bleeding, embolization should be combined according to the patient's hemodynamics, which may result in its extended application. PMID- 2586463 TI - [Evaluation of endoscopic local injection of hypertonic saline- epinephrine solution and surgical treatment on hemorrhagic gastroduodenal ulcer]. AB - For the purpose of arresting hemorrhage from gastric and duodenal ulcer we developed a method of endoscopic local injection of hypertonic saline-epinephrine solution (HSE), consisting of 625mEq/L or 1,250mEq/L sodium chloride with 0.05mg/ml epinephrine. During the period between October 1978 and March 1988, a total 246 patients with peptic ulcers underwent treatment for hemostasis by this method. According to our criteria for the assessment of the hemostatic effect, 231(93.9%) of 246 cases achieved permanent hemostasis, 7(2.8%) achieved temporary hemostasis, and no effect was noted 8 cases (3.3%). From June 1975 to March 1988, a total 366 cases with gastric and duodenal ulcers were operated on at our hospital. By applying endoscopic local injection of HSE, the rate of emergency operation for patients with bleeding peptic ulcers was significantly reduced from 13.4%(22/164) to 1.5%(3/202). From these results, we consider that endoscopic local injection of HSE is valuable for hemorrhage from gastric and duodenal ulcer. PMID- 2586464 TI - [Clinical features and treatment of lower intestinal hemorrhage]. AB - We have experienced 471 patients with anal bleeding during the past seven years. The Results are as follows: 1. As for the types of disease, incidence of hemorrhoid, colorectal cancer and ulcerative colitis (UC) was high, while that of small intestinal problems was low. 2. In the cases of remarkable bleeding from the lower intestinal tract, massive or acute progressive bleeding was less frequent than expected. 3. Inflammatory diseases were the main causes of massive bleeding. Bleeding by UC was the major indication for urgent operation. In the cases with acute massive hemorrhage, basic complications were often found and the possibility of the diseases of small intestine and blood vessel disorders also should be considered. 4. At the examination of bleeding patients, it is efficient to explore the lower colon and rectum first by colonoscopy or sigmoidoscopy, for most of the bleeding lesions are found in these portions. 5. As for surgical treatment, most of colorectal cancer patients with hemorrhage are able to be operated with wait- and -see management. For UC patients, complete cure operation is possible even if they have high-dose steroid medication. PMID- 2586465 TI - [Gastrointestinal bleeding in children]. AB - The site and nature of lesions producing gastrointestinal bleeding was evaluated in pediatric patients admitted to Tokai University Hospital. The differential diagnosis was possible based upon the character of the bleeding and the age of the patient. Upper endoscopy is the diagnostic maneuver of choice in evaluating the upper gastrointestinal bleeders. Sigmoidoscopy, colonoscopy, technetium scans, tagged red cell scans and intraoperative angiography were helpful in locating bleeding sites of lower bleeders. Common causes of bleeding were as follows: Hemorrhagic disease, necrotizing enterocolitis, and midgut volvulus in neonates; intussusception and internal hernia in infants; juvenile polyp and infectious diarrhea in children; duodenal ulcer and ulcerative colitis in adolescents. Gastro-duodenal ulcers were found in all age groups. One neonate died of indomethacin induced bleeding, however, bleeding from acute ulcer was usually controlled by conservative treatments. Increasing frequency of variceal bleeding due to portal hypertension after successful Kasai procedure for congenital biliary atresia was emphasized. PMID- 2586466 TI - [Clinical significance of measurement of nuclear DNA content in breast cancer]. AB - Nuclear DNA content measured by a cytofluorometric method was investigated to evaluate its clinical significance in 73 cases with breast cancer which had extended radical mastectomy. Many cases of D type (diploid type) which had a prominent peak at the 2c region (control DNA content of lymphocytes) were safe indications for modified radical mastectomy. Bone recurrence was significantly more frequent in D type than in N type (non-diploid type) which did not have a prominent peak at the 2c region. Because D type had high positive rate of hormone receptors, endocrine therapy might be effective for many cases. Local or lung recurrence was more common in cases with N type which had a significant low cumulative survival rate compared with D type and especially N type 4c-3 of which over 4c cells more than 30% had the poorest prognosis. Therefore, multidisciplinary treatment composed of extended operation, radiation and chemotherapy was necessary to improve the prognosis of breast cancer patients with N type 4c-3. It was concluded that the measurement of nuclear DNA content in breast cancer might be useful for decision of therapy suitable for each case based on malignancy grading. PMID- 2586467 TI - [Nuclear DNA content of gastric cancer with biologically high malignancy]. AB - Nuclear DNA content was microspectrophotometrically measured in 120 gastric cancer patients to assess the predominance of a particular DNA distribution pattern in gastric cancer with biologically high malignancy, such as the marked tendency for severe vessel invasion and remote metastasis, and for early recurrence after curative surgery. DNA distribution patterns were grouped into low and high ploidies, and the correlation between the DNA ploidy pattern and histopathologic, biologic findings was evaluated. The incidence of high DNA ploidy tended to be increased as the histological stage and level of infiltration progressed. On the other hand, the incidence of high DNA ploidy was higher in dead cases of early recurrence among cases of the same histological stage, or where vessel invasion and remote metastasis were severe among cases of the same depth of invasion. Therefore, we consider that the DNA distribution pattern well reflects the malignancy of gastric cancer. PMID- 2586468 TI - [Flow cytometric DNA analysis in colorectal cancer]. AB - Flow cytometric DNA analysis for assessing malignant potential of colorectal carcinoma was investigated by paraffin-embedded materials. Preservation time of paraffin blocks and formalin fixation time of surgical specimens within 14 days do not influence the nuclear DNA content. There was seen a good correlation between the DNA contents of paraffin-embedded and fresh materials obtained from the same surgical specimens. Using deparaffinized tumor specimens, the nuclear DNA content was measured by flow cytometry in 144 patients with primary colorectal cancer, who had been treated from 1971 to 1985. Forty-four percent of colorectal cancer were diploid and 56% were aneuploid. There was no significant correlation between ploidy pattern and clinicopathological factors. However, the patients with aneuploid tumor had a significantly worse survival than those with diploid tumor (Generalized Wilcoxon test, p less than 0.001). The patients with aneuploid seemed to have an unfavorable survival than those with diploid in the same stage, and had a significantly worse survival in each group of negative nodes, P0 and H0. It is concluded, therefore, that the nuclear DNA content of colorectal cancer may be an important prognostic factor, being independent of pathological stage. PMID- 2586469 TI - [Detection of cellular DNA strand breaks induced by antitumor drug and heat using in situ nick translation]. AB - Cellular DNA strand break induced by an alkylating agent: Carboquone (CQ), and heat (43 degrees C) was detected in HeLa cells in vitro and mouse sarcoma-180 cells in vivo. The break sites in the DNA were translated artificially in the presence of Escherichia coli DNA polymerase I and [3H]-labeled dTTP and sites in the DNA were visualized by autoradiographic observation of grains in the nuclei. These breaks increased in a dose and time dependent manner, compared to findings in the control cells. Our findings show that the surviving response of cells decreases while the level of DNA strand breaks increases following exposure to CQ or heat. The nick translation method is a rapid in situ assay for determining drug and heat induced DNA damage of tumor cells, under in vitro and in vivo conditions and in a semi-quantitative manner. PMID- 2586470 TI - [Nd-YAG laser therapy in the field of pulmonary surgery]. AB - Since 1980, we have treated 71 patients with malignant tumors and benign lesions by the Nd-YAG laser. The flexible fiberoptic bronchoscope with the local anesthesia was used for the treatments. Fifty-four cases were malignant tumors and 17 were benign lesions involving trachea and/or hilar bronchus. In malignant tumors, 41 cases were lung cancers, 24 of which were squamous cell carcinomas. Of 17 cases of benign lesions, 10 (58.5%) were introgenic stenoses. Palliative treatments were done for 36 cases of lung cancers, of which 23 died within 1 year after treatments. Four of 5 cases, which survived beyond 2 years, were adenoid cystic carcinomas. In 17 benign cases, 13 (76.5%) showed distinct improvements of symptoms and findings after treatments. Three patients died of massive bleedings. In these cases, severe stenoses were observed, which required treatments repeatedly. With the proper knowledge of the indications, limitations and complications, of YAG laser therapy it can be a beneficial mean for the management of benign lesions and malignant tumors in trachea and hilar bronchus. PMID- 2586471 TI - [Surgical application of low-power laser: experimental study, development of equipments and clinical application]. AB - We carried out experimental and clinical studies with low-power laser to perform the surgical application. The developed device for microvascular anastomosis with semiconductor laser diode made of In-Ga-As-P was used to perform 15 end-to-end laser assisted microvascular anastomoses of carotid arteries in rabbits. In four of 7 cases which were irradiated with power output 50mW showed patency immediately after surgery with no wound disruption. A new medical device with Ga A1-As semiconductor laser diode was developed for pain relief. A double-blind evaluation of the test was initiated in 124 patients suffering from chronic inflammatory pain. Result is that of 63 patients irradiated laser, 45(71%) were effective and of 61 cases not irradiated laser, 8(13%) were relieved pain. The data were analyzed statistically by chi square, and criterion for statistical significance was the 0.01 level. The spectral properties of laser-excited fluorescence of three photosensitizers, namely tetracycline, hematoporphyrin free base and chlorin e6Na, taken up in human arterial intima were detected. Photosensitizers were administrated to resected human arteries for 2 hours in vitro. The main results are following: 1) Photosensitizers are confirmed to be taken up in arterial intima and the fluorescence intensity decreases as the time goes on. 2) The fluorescence intensity from atheromatous plaque is usually stronger than that from normal region. PMID- 2586472 TI - [Experimental and clinical studies on the laser application in the cardiovascular surgery; analysis of clinical experience of 112 patients]. AB - Since 1980, we have applied lasers experimentally in the following three categories in the fields of cardiovascular surgery. That is, Group 1: New myocardial revascularization in the patients whose coronary arteries are too small or diffuse due to atherosclerosis, Group 2: Laser vascular anastomosis especially for small-caliber vessels, such as coronary artery bypass grafting, Group 3: Laser angioplasty for obstructive arterial disease. Subsequently, efficacy of laser application could be obviously recognized in these fields. On the basis of excellent results of our experimental studies, laser was clinically employed for 112 patients with anginal pain, intermittent claudication and renal failure. They consisted of new myocardial revascularization in one case and vascular anastomosis in 89 cases including 7 cases (LIMA-LAD2, SVG-LAD5) of the coronary artery bypass grafting and laser angioplasty in 22 cases including 5 cases (LAD3, RCA2) of intraoperative laser coronary angioplasty. Optimal conditions of vascular anastomosis were 20-40mW in output and 6-12sec/mm in irradiation time. On the other hand, optimal conditions for laser angioplasty were 6 watts in output and 3sec in irradiation time for each shot. Laser irradiation was carefully repeated according to the grade of atherosclerotic changes. These patients are doing well without any complications throughout laser. Our experimental and clinical experiences of laser application in the fields of the cardiovascular surgery were presented in detail. PMID- 2586473 TI - [Photodynamic therapy--its application for the treatment of esophageal cancer]. AB - Effect of Photodynamic therapy (PDT) for esophageal cancer was discussed in this study. PDT has been performed on 9 cases of superficial esophageal cancer. All cases were followed periodically by endoscopy for 2 years 2 months to 6 years and no case has any local recurrence. But in 2 cases invaded submucosal layer, lymph node metastasis was recognized. We think PDT is one of the very effective therapies in the treatment of intramucosal cancer. PMID- 2586475 TI - [Lithotomy of bile duct stones by flash-lamp-pumped dye laser]. AB - Laser therapy for bile duct stones, such as the non-contact beam treatment using continuous wave of Nd:YAG laser or contact beam treatment using ceramics rod, has been done in our institution from 1980. As a result, the ratio of complete lithotomy has been increased from 31/47 (66%) to 66/71 (93%). Recently, we had a opportunity to use the Lasertripter by Candera Corp., which was devised for urinary stones. It beams pulse wave to crush stones. The effectiveness of this new laser lithotripsy is different according to the kind of the stones, but it is better than that of conventional YAG laser. Furthermore, as this method can be used with thin fiberscope, this method is more effective to peripheral intrahepatic stones than YAG laser. PMID- 2586474 TI - [Application of transendoscopic Nd-YAG laser to stenosis caused by unresectable carcinoma of the alimentary tract]. AB - Clinical and pathological studies were performed on the efficacy of transendoscopic Nd-YAG laser irradiation to stenosis by unresectable carcinoma of the alimentary tract, and the following conclusions were obtained. Nd-YAG laser was irradiated with 30-40W, total energy 3,000-12,000J, to carcinoma of 8 cases of the esophagus, 4 cases of the stomach, 7 cases of recurrence at gastric anastomosis site and 4 cases of the large intestine, and it evaporated and reduced tumor to relieve of stenosis. The patients's quality of life was remarkably improved. Pathological study on biopsied specimens at the site of irradiation revealed no residual viable cancer cell within at least 6mm depth from the surface of carbonization layer. No perforation, no massive bleeding, no pain were recognized both during and after irradiation. PMID- 2586476 TI - [The significance of the extensive systematic lymphadenectomy for thoracic esophageal carcinoma]. AB - 1. MATERIALS: One hundred and seventy nine patients with thoracic esophageal carcinoma who underwent an intrathoracic esophagectomy combined with systematic lymphadenectomy were investigated. They were roughly classified into two groups, i.e., those who received extensive lymphadenectomy in bilateral cervical and upper mediastinal regions (A group: 78 subjects), and those who underwent ordinary limited dissection of the lymph nodes in the left cervical and upper mediastinum (B group: 101 subjects). 2. RESULTS: Cumulative 5-year survival rate of advanced cancer patients was 31.3% in A and 22.5% in B, the difference being of significance (p less than 0.05). The rate of postoperative mortality showed no difference between both groups, i.e., 3.8% in A and 4.9% in B groups. However, the incidence of postoperative pulmonary complication was 17.9% in A and 13.9% in B. Recurrent nerve palsy developed in frequencies of 39.7% and 17.8% in A and B groups respectively. 3. CONCLUSION: The degree of extended lymph node metastasis in carcinoma of the thoracic esophagus was closely correlated with its prognosis, and hence it is extremely important to perform intrathoracic esophagectomy with extensive systematic lymphadenectomy aiming at the favorable result in surgical treatment. It is also required to take preventive measures against postoperative complications. PMID- 2586477 TI - [Clinical evaluation of systematic lymph node dissection for the intrathoracic esophageal carcinoma]. AB - We evaluated the effectiveness and complication of systematic lymph node dissection for the intrathoracic esophageal carcinoma, which includes cervical, intrathoracic and abdominal lymph node dissection. Two hundred and thirteen individuals with intrathoracic esophageal carcinoma underwent esophageal resection in the Department of Surgery II, Kyushu University from 1979 to 1988. Of these 213, systematic lymph node dissection in addition to esophageal resection was performed on 19 patients. Lymph node recurrence has been reduced with this procedure and survival rate was more favorable in the cases with systematic lymph node dissection than those without it at present. On the other hand, although the occurrence of postoperative recurrent nerve palsy in the cases with systematic lymph node dissection and in those without it were 47.4 and 11.9%, rates of postoperative pulmonary complications were 5.2 and 16.0%, respectively. Operative death was none in those with systematic lymph node dissection. Therefore, this procedure has been performed in safety with intensive perioperative cares and it would contribute more favorable prognosis. PMID- 2586478 TI - [Evaluation of the collo-thoraco-abdominal dissection for the intrathoracic esophageal carcinoma]. AB - Five hundred and forty three cases of intrathoracic esophageal carcinoma were reviewed. Of these, one hundred and sixty one cases had collo-thoraco-abdominal (CTA) dissection and three hundred and eighty two cases had thoraco-abdominal (TA) dissection. Postoperative pulmonary complications occurred in 35.5% of the patients who had CTA dissection and in 18.0% of those who had TA dissection. Incidences of postoperative hoarseness of voice and anastomotic leakage were almost similar in the two groups. However, the mortality rates within 30 postoperative days was 4.3% for the CTA groups compared to 1.8% for the TA group. The average number of lymph nodes resected per case was much higher in the CTA group than than the TA group. This implied that the dissection was more extensively performed in the CTA group involving not only bilateral cervical regions but also the upper mediastinum continuing into the neck. Better 1, 2 and 3 years survival rates were observed in the CTA group than the TA group, but for the 4, 5 years survival rates there was no statistical difference noted. For stage-0 and stage-4 carcinoma of the upper third esophagus, marked improvement in the survival rates were obtained in the CTA dissection cases. In conclusion, collo-thoraco-abdominal dissection can be justified for the surgical treatment of intrathoracic esophageal carcinoma despite its postoperative mortality rate of 4.3%. PMID- 2586479 TI - [An assessment of extended lymphadenectomy including cervical node dissection for cancer of the thoracic esophagus]. AB - An extended lymphadenectomy including cervical node dissection is one of the most difficult operations, therefore its merits and demerits should be assessed in order to evaluate whether it has the significance of extended radical operation or not. Extended lymphadenectomies including cervical node dissection became to be the standard procedures of lymphadenectomy for cases with cancer of the thoracic esophagus from 1986, and were carried out in 42 cases. Survival rates, disease free survival rates, sites of recurrences and incidences of postoperative complications were compared with the of cases with conventional lymphadenectomy excluding cervical node dissection. Concerning over all survival rates, no significant differences were observed between extended and conventional groups. However only in cases of stage 0 I II, significant difference in survival rates were observed between two groups. Therefore based on our experience, the merit of extended lymphadenectomy was observed only in stage 0 I II cases which had no lymph node metastasis. Concerning the incidence of postoperative complications, no significant differences were observed between two groups, therefore the significance of proceeding extended lymphadenectomy was confirmed. PMID- 2586481 TI - [Cervico-thoracic-abdominal lymph node dissection for carcinoma of the thoracic esophagus]. AB - Over the period from 1982 to 1988, 127 cases with carcinoma in the thoracic esophagus underwent curative resection through a right thoracotomy. Cervicothoracic-abdominal lymph node dissection was performed in twenty-seven cases. No operative death occurred and only one hospital death (4%) was recorded. The only postoperative complication was recurrent laryngeal nerve palsy. Based on the adjusted survival-rate curves using Cox's method, there was significant difference in prognosis in favor of these 27 cases that received cervicothoracic abdominal lymph node dissection over those that did not. The survival rate of all curatively operated cases was noticeably improved by using this procedure. Of those that underwent dissection only, or dissection with postoperative radiotherapy or chemotherapy, the best prognosis could be reached by a combination of the cervicothoracic-abdominal lymph node dissection and postoperative chemotherapy. From follow-up data regarding recurrence rates, a more extended dissection and complete removal of lymph nodes in the left upper mediastinum and retroperitoneum should further improve the long-term prognosis. PMID- 2586480 TI - [Benefits and risks associated with dissection of three regional lymph nodes (bilateral cervical, thoracic and abdominal) in thoracic esophageal carcinoma]. AB - To obtain curability safely, we have employed dissection of three regional lymph nodes (the bilateral cervical, thoracic and abdominal lymph nodes) since 1983. The subjects were 111 (three regional group) of 158 patients with thoracic esophageal carcinoma operated on our department till 1988. When compared to 207 patients treated during the period from 1973 to 1982 (control group), the background factors of the subjects revealed that the three regional group included more patients with advanced carcinoma and more elderly patients over 70 years of age. Operative results were more favourable in the three regional group (5.3% vs 2.7%), although mean operative time was longer (5 hrs and 2 min vs 8 hrs and 38 min) and mean blood loss was higher (1,098ml vs 1,407ml). Moreover, the incidence of recurrent nerve paralysis was higher. Overall 5-year survival was 20.4% vs 22.3%, showing no significant difference. However, when stage distribution is taken into consideration, results in the three regional group may be regarded as improved. After dissection of the three regional lymphnodes, the pattern of lymph node metastasis of thoracic esophageal carcinoma has been made clearer to give useful information on the site in which further dissection of lymph node is required. PMID- 2586482 TI - [Efficacy of extended radical operation based on preoperative staging]. AB - From 1985 to 1988, we have resected 203 cases of the thoracic esophageal cancer with right thoracotomy. Those 203 cases were classified as R3 (bilateral cervical, thoracic and abdominal node dissection), R2 + alpha (left cervical, thoracic and abdominal nodes dissection) and R2 (thoracic and abdominal node dissection) based on preoperative staging. The background of R3 mainly contained Iu cases, advanced cases, positive cases of upper mediastinal metastasis, and that of R2 mostly contained high aged and risk cases, though this group showed low LN metastasis. The incidence of postoperative complications were higher R3 greater than R2 greater than R2 + alpha in order. Pneumonia had no relationship to neck dissection. Recurrent nerve palsy was recognized in R3 group about 16%. Operative mortality mostly belong to high aged group over 70 y.or., noncurative cases and R3 group. The survival rate of C greater than 0 resected cases with right thoracotomy after 1985 showed some improvement compared with the cases of standard R2 dissection by right thoracotomy from 1980-1984. It showed no difference of the curative survival curve among R3, R2 + alpha and R2 groups. Thus, it is effective to improve the survival rate of resected esophageal cancer with our indication based on preoperative staging. PMID- 2586483 TI - [advantages and disadvantages of three regional lymph node dissection of thoracic esophageal carcinoma and the lymph node dissection by thoraco-abdomino-midsternal approach]. AB - The 117 cases of two regional (thoraco-abdominal) lymph node dissection were compared to the 56 cases of three regional (with neck area in addition) lymph node dissection for esophageal carcinoma. As for operative death and postoperative complications, there were no difference between these two groups. The prognosis of three regional dissecting group was better than that of two regional dissecting group concerning about the cases that lymph node metastases were less than 1 or 2, the depth of invasion was limited to just near adventitia (a1) and the locations were in upper or midthoracic esophagus. But also the rate of postoperative recurrence to the neck and uppermediastinal lymph nodes were high in spite of three regional dissection. Putting together with all cases, significant improvement of prognosis were not obtained in the three regional group compared to two regional group. So we thought the usual three regional lymph node dissection might not be sufficient. Recently we added midsternotomy and made the lymph node dissection in neck-thoracic junction more complete. This procedure did not make the operative death and postoperative complications increase and the improvement of prognosis was expected by it. PMID- 2586484 TI - Duplications created by transformation in Sordaria macrospora are not inactivated during meiosis. AB - We present here the first report of a transformation system developed for the filamentous fungus Sordaria macrospora. Protoplasts from a ura-5 strain were transformed using the cloned Sordaria gene at a frequency of 2 x 10(-5) transformants per viable protoplast (10 per microgram of DNA). Transformation occurred by integration of the donor sequences in the chromosomes of the recipient strain. In 71 cases out of 74, integration occurred outside the ura5 locus; frequently several (two to four) copies were found at a unique integration site. Using the advantage of the spore colour phenotype of the ura5-1 marker, we have shown that the transformed phenotype is stable through mitosis and meiosis in all transformants analysed. No methylation of the duplicated sequences could be observed during meiotic divisions in the transformants. PMID- 2586485 TI - Expression of two gas vacuole protein genes in Halobacterium halobium and other related species. AB - The archaebacterium Halobacterium halobium contains two genes encoding gas vacuole proteins (vac). One resides on a large naturally occurring plasmid and encodes a protein of 76 amino acids (p-vac), while the other is a chromosomal gene that encodes a highly similar protein of 79 amino acids (c-vac). Northern analysis determined the c-vac and p-vac mRNA to be approximately 340 nucleotides in length, and S1 mapping of both transcripts indicated that the 5' terminus for each starts at the same relative nucleotide. Three other Halobacterium species producing gas vacuoles were investigated, H. spec. GN101, YC819-9, and SB3. All three contain only a chromosomal c-vac gene, and the 5' terminus of the 340 nucleotide mRNA starts at the same nucleotide as found for H. halobium. The c-vac gene region of H. spec. GN101 contains nine nucleotide exchanges, three of which occur in the coding region with no effect on the amino acid sequence. In contrast, the c-vac gene of H. spec. SB3 has an identical nucleotide sequence to the H. halobium c-vac gene. Gas vacuole production in each of these species was monitored during culture growth by phase contrast microscopy, and the vac mRNA level was determined for each time point. H. halobium p-vac deletion mutants, as well as the halobacterial species GN101 and YC819-9, start to synthesize gas vacuoles in early stationary growth phase with a maximal mRNA content in stationary phase. In contrast, H. halobium wild-type synthesizes gas vacuoles exclusively due to p-vac gene expression with a maximal mRNA level during logarithmic growth, and transcripts of the c-vac gene were not detectable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2586487 TI - Rat brain dendrotoxin receptors associated with voltage-gated potassium channels: dendrotoxin binding and receptor solubilization. AB - Venom from the green mamba, Dendroaspis angusticeps, contains four polypeptides termed dendrotoxins (DaTXs) that block brain Ca-independent voltage-gated K channels. We compared the binding to rat brain receptors of two of these DTXs, alpha-DaTX and beta-DaTX, which preferentially block inactivating and noninactivating K channels, respectively. 125I-alpha-DaTX and 125I-beta-DaTX bind to single classes of receptor sites on synaptic membranes (KD = 0.7 and 36 nM for alpha-DaTX and beta-DaTX, respectively), with pH optima of about 6.5. The binding of both iodinated toxins was optimal in solutions containing 150 mM NaCl and decreased as Na was replaced with other alkali metal ions; the rank order for support of toxin binding was Na greater than K greater than Li greater than Rb. Cs (IC50 = 5-6 mM) prevented toxin binding, as did the divalent cations Ba and Ca (IC50 = 4-6 and 9-13 mM, respectively). The inhibition of 125I-alpha-DaTX binding by Cs and Ba was noncompetitive. The displacement of 125I-alpha-DaTX and 125I beta-DaTX binding by the four unlabeled DaTXs was similar; the relative potency was alpha-DaTX greater than beta-DaTX greater than gamma-DaTX. The displacement curve for delta-DaTX did not parallel the others. When cross-linked with dimethylsuberimidate, both iodinated toxins covalently labeled membrane polypeptides of similar molecular weight (Mr = 65,000). The alpha-DaTX and beta DaTX receptors were solubilized from rat synaptic membranes. Toxin binding to the soluble from rat synaptic membranes. Toxin binding to the soluble receptors was preserved in the presence of K and lecithin and decreased as K was replaced with Rb greater than Cs greater than Li greater than Na. The affinity of 125I-alpha DaTX for the solubilized receptor was decreased 10-fold (KD = 7 nM); the affinity of 125I-beta-DaTX was decreased 3.5-fold (KD = 124 nM). However, the four unlabeled DaTXs retained their relative potencies for the inhibition of 125I alpha-DaTX binding. The molecular weight of the solubilized receptor was estimated to be about 270,000 by sucrose density gradient centrifugation. These data raise the possibility that the inactivating ("A-type") and noninactivating voltage-gated K channels in rat brain may have similar subunits and that the channels may be composed of four Mr 65,000 polypeptides. PMID- 2586486 TI - Isolation and initial characterization of a Schizosaccharomyces pombe mutant exhibiting temperature-dependent radiation sensitivity due to a mutation in a previously unidentified rad locus. AB - We have isolated a mutant of the yeast Schizosaccharomyces pombe which exhibits sensitivity to UV light when grown at either 30 degrees or 37 degrees C, as compared to the parental wild-type strain. This increased sensitivity is more pronounced when cells are grown at 37 degrees C. The mutant is also sensitive to 18 MeV electrons at the high temperature. Tetrad analysis of spores generated by crossing the mutant and a Rad+ strain revealed that sensitivity to both types of radiation cosegregate 2:2, relative to wild-type resistance, indicating that a single altered chromosomal locus is responsible for the radiation sensitivities observed. In addition, analysis of spores resulting from crosses between the mutant and all other known S. pombe rad mutants indicates that the temperature dependent sensitivity described in this report is mediated by a mutation in a previously unidentified rad locus. PMID- 2586488 TI - Role of microtubule assembly in phenytoin teratogenic action in the sea urchin (Arbacia punctulata) embryo. AB - We evaluated the role of microtubule assembly in phenytoin (5-5 diphenylhydantoin) teratogenic activity in the sea urchin embryo. Zygotes were exposed to phenytoin or one of several phenytoin analogs within 15 min of fertilization and the frequency of the resultant malformations was assessed at the cleavage and late gastrula (prism) stages. Concomitant studies of drug uptake into zygotes and drug effects on both microtubule assembly in vitro and spindle morphology in situ were also performed. Phenytoin, 5-p-methylphenyl-5 phenylhydantoin, and 5-p-methoxyphenyl-5-phenylhydantoin were teratogenic (approaching 100% affected embryos) at both developmental stages were concentrated rapidly by the zygotes, and induced a shortened mitotic spindle in situ. In a separate in vitro system using porcine brain microtubular protein, these analogs were shown to inhibit microtubule assembly directly. The major human metabolite of phenytoin, 5-p-hydroxyphenyl-5-phenylhydantoin was teratogenic at the prism stage but induced only a 20% incidence of abnormal embryos at the first cleavage. This was attributed to the slow rate of uptake of this analog. This compound inhibited microtubule assembly in the in vitro assay and also shortened the mitotic spindle to an extent proportional to its observed weak effect on the first cleavage. Another analog, 5-p-hydroxyphenyl-5-p' methylphenylhydantoin was not teratogenic at concentrations up to the limit of its solubility (285 microM). If this analog were as potent inside the cell as either phenyltoin or 5-p-hydroxyphenyl-5-phenylhydantoin, the intracellular concentrations achieved should have been sufficient to induce abnormal cleavage. Thus, the lack of teratogenic efficacy of this analog was correlated with its observed lack of effects on either microtubule assembly in vitro or spindle formation in situ. The anticonvulsant drug ethotoin was not teratogenic at concentrations up to 2.93 mM, apparently due to either poor uptake or inability to inhibit microtubule assembly or both. Overall, these studies are consistent with a hypothesis that phenytoin may induce abnormal development in this system by a direct inhibition of microtubule assembly. PMID- 2586489 TI - Suppression of hepatic levels of an ethanol-inducible P-450DM/j by growth hormone: relationship between the increased level of P-450DM/j and depletion of growth hormone in diabetes. AB - The mechanism of the suppression of an ethanol-inducible cytochrome P-450 (P 450DM/j) by pituitary hormone has been studied in rats. The hepatic content of P 450DM/j protein quantitated by Western blots was low but was 2-fold higher in male than female untreated rats (75 and 34 pmol/mg of protein, respectively). The content was increased 2.6-fold (male) and 5.6-fold (female) by hypophysectomy and the sex-related difference was abolished. Treatment of hypophysectomized rats with human growth hormone (hGH), but not with prolactin, reversed the increased amounts of P-450DM/j protein. The hGH-induced suppression was more effective with the continuous infusion than intermittent injection. The hepatic level of P 450DM/j mRNA, determined by the use of a 23-mer oligonucleotide probe, was also changed by hypophysectomy and/or hGH-treatment, largely in parallel with the changes in the content of P-450DM/j protein and microsomal p-nitrophenol and aniline hydroxylations. These results suggest that growth hormone exerts the suppressive effect on P-450DM/j through a somatogenic receptor-mediated process. In another growth hormone-depleted condition, diabetes, the hepatic level of P 450DM/j mRNA was also increased to a level similar to that in hypophysectomized rats, but the protein content was 2- to 3-fold higher in diabetic than hypophysectomized rats. These results indicate, in addition to the reduction of serum growth hormone level, the presence of another stimulatory factor, which acts translationally or posttranslationally in livers of diabetic rats. On the other hand, coordinate changes in the level of P-450DM/j protein and the mRNA in hypophysectomized rats indicate that growth hormone acts rather directly and suppresses the level of P-450DM/j mainly at a pretranslational step in rat livers. PMID- 2586490 TI - Relative substrate activities of structurally related pteridine, quinazoline, and pyrimidine analogs for mouse liver folylpolyglutamate synthetase. AB - Several structurally related series of folate analogs were studied as substrates for mouse liver folylpolyglutamate synthetase (FPGS). A comparison of the kinetics of the interaction of this enzyme with folate analogs that contained the quinazoline ring in place of the pteridine ring with those of the analogous pteridines demonstrated that the quinazoline derivatives were more efficient substrates for and tighter binding inhibitors of this enzyme. A series of 2,4 diaminopyrimidine dihydrofolate reductase inhibitors were found to be substrates for FPGS; these are the first known compounds without a fused ring system analogous to the pteridine ring of the folate molecule that are substrates for FPGS. Several 5,8-dideazafolate derivatives that lack the 2-amino group had activity as substrates for FPGS equivalent to that of the corresponding 5,8 dideazafolates. When a homologous series of 5,8-dideazafolic acid analogs with hydrocarbon substituents on the 10-nitrogen were studied, these substituents were found to diminish the efficiency of utilization of these analogs as substrates for FPGS; this effect increased with increasing chain length of the hydrocarbon. It was concluded that neither the 2-amino group nor an intact pyrazine ring of folates and folate analogs are essential for the binding of folates to the active site of mouse liver FPGS but that the pyrazine ring probably serves to position other regions of the folate molecule that interact with amino acid residues in the active site. It was also inferred from these observations that the volume within the active site of FPGS above/below the pyrazine ring or near the 10 position of folate derivatives are regions of limited bulk tolerance; binding of folate analogs with substituents at these positions probably distorts the active site. PMID- 2586491 TI - Distance geometry of alpha-substituted 2,2-diphenylpropionate antimuscarinics. AB - Quantitative structure-activity relationships between pharmacological activities and physical properties of a series of 2,2-diphenylpropionate compounds were used to define the topography of the antagonist binding site of muscarinic receptors. XICAMM, a computer molecular modeling program, was used to calculate geometrical and topological values of the compounds. The compounds were tested for their antimuscarinic activities by: (a) inhibition of [N-methyl-3H]scopolamine binding to the muscarinic receptors of N4TG1 neuroblastoma cells, (b) inhibition of carbachol-induced alpha-amylase release from rat pancreas acini, and (c) blocking of acetylcholine-induced contraction of guinea pig ileum. To evaluate as clearly as possible only the effect of the bond distance on the potency of the synthesized antimuscarinics, the compounds contained as many constant features as possible. Neither the hydrophobic nor the ester moieties of the compounds were changed, and the rings containing the protonated nitrogen were saturated and restricted. The antimuscarinic activities obtained from the three assays were significantly correlated with each other, with the exception of two compounds, 9 and 13. The latter two compounds demonstrated specificity for the m3 muscarinic receptor subtype expressed in the pancreas. Furthermore, it was demonstrated that the antimuscarinic activities were significantly related to the bond distances between the carbonyl oxygen (constant electronegative locus) and the protonated nitrogen (center of cationic charge) of the 2,2-diphenylpropionate compounds. Parabolic relationships between the pharmacological activities and bond distances were empirically established. The shortest calculated bond distance of these compounds was approximately 4.4 A, whereas the longest was about 5.9 A. The maximum antimuscarinic potency was observed with a calculated bond distance of about 5.2 A in all three assays. PMID- 2586492 TI - Manoalide: structure-activity studies and definition of the pharmacophore for phospholipase A2 inactivation. AB - Manoalide is a potent antiinflammatory marine natural product and a direct inactivator of venom phospholipase A2 (PLA2; EC 3.1.1.4). Manoalide has been shown to irreversibly inhibit PLA2, with the corresponding modification of a selective number of lysine residues. The mechanism of inactivation has not yet been elucidated and structure-activity relationship studies were, therefore, performed in order to determine the contributions of the various functional groups incorporated in the gamma-hydroxybutenolide, alpha-hydroxydihydropyran, and trimethylcyclohexenyl ring systems to the efficacy (irreversibility) and potency of this series of inhibitors. These studies indicate that 1) the presence of the hemiacetal in the alpha-hydroxydihydropyran ring is required for irreversible binding of manoalide, 2) the gamma-hydroxybutenolide ring is involved in the initial interaction of manoalide with PLA2, and 3) the hydrophobic nature of the trimethylcyclohexenyl ring system allows nonbonded interactions between manoalide and PLA2 that enhance the potency of these analogs. These structure-activity relationship studies suggest that the closed ring form of manoalide is the predominant molecular species that accounts for the selective and potent inhibition of PLA2 by manoalide. Elucidation of the mechanism awaits further detailed physicochemical studies on the structure of the manoalide (analog)-protein adducts in model systems and using PLA2. PMID- 2586493 TI - Serum cholinesterase isoenzymes and the WHHL rabbit: the relationship between the activity of cholinesterase not bound to low-density-lipoprotein and lipoprotein titer. AB - Serum cholinesterase has been previously shown to complex with beta-lipoprotein in the plasma. Since serum cholinesterase exists as isoenzymes in plasma, the relationship between the activity of these isoenzymes (unbound to beta lipoprotein) and lipoprotein titer was investigated. The results indicated that the total of C2, C3, and C4 isoenzyme activities were expressed within a narrow range and independent of low density lipoprotein titer. These findings may indicate that unbound plasma cholinesterase may undergo autoregulation independent of cholinesterase bound to beta-lipoprotein. PMID- 2586494 TI - Interactions among phospholipids of guinea pig rough microsomes, effect of fat deficiency. AB - The fatty acid composition and the steady-state fluorescence anisotropy (rs) of 1,6-diphenyl-1,3,5-hexatriene (DPH) were determined for each of the five major phospholipid (PL) classes present in the liver rough microsomes (RM) of guinea pigs fed with control and fat-deprived diets. In order to obtain information about PL-PL interactions and their contribution to the overall membrane fluidity the experimental rs of phospholipid mixtures were compared to the molar weighed average values of the individual phospholipid rs values. The PL ratios in the mixtures were the same to those found in the RM membranes. Binary mixtures of phosphatidylcholine (PC) with phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI) and sphingomyelin (SM) show higher values of rs than those estimated from the individual component parameters indicating a 'rigidizing' interaction. The rigidizing effect of PE was also observed when this phospholipid was sonicated with mixtures of PC with PS and PI. However, no rigidizing effect of PE was observed in the PC bilayers when SM was included in the composition suggesting that PE-SM interactions prevent 'rigidizing' effects of PE. Besides, in spite that PC-PI and PC-PS mixtures have 'rigidizing' interactions, the incorporation of PI and PS to PC-PS and PC-PI mixtures, respectively, have a 'fluidizing' effect. In consequence, phospholipid polar head groups interact in RM membranes modifying the molecular packing and/or the rotational diffusion of acyl chains. The complexity and variety of constituent phospholipids could prevent major changes in the fluidity. The comparison of results obtained with PL mixtures of control and fat-deficient animals indicate that a change in the number of double bonds does not evoke a significant difference between either the 'rigidizing' of 'fluidizing' effects. However, there is a general tendency indicating that phospholipids with higher double bond index evoke lower 'rigidizing' and 'fluidizing' interactions. Moreover, PL of animals fed a fat-deficient diet have less fluidity than those of control animals. PMID- 2586495 TI - Comparison of polyamine and S-adenosylmethionine contents of growing and encysted Acanthamoeba isolates. AB - We have used High Performance Liquid Chromatography to determine metabolite characteristics of three recent isolates of Acanthamoeba which exhibit cultural characteristics consistent with those of established potential pathogens. Growing amoebae and dormant cysts of these isolates were explored in regard to their qualitative and quantitative intracellular levels of polyamine and S adenosylmethionine metabolites. The polyamine found in the greatest concentration in the growing cells was 1,3-diaminopropane (DAP), followed by spermidine (SPD). A low level of putrescine was also found in the growing cells. These polyamines significantly decreased in concentration as the amoebae differentiated to cysts. N8-acetylspermidine and acetylspermine were found in both developmental stages while acetylcadaverine was found only in growing amoebae and N1-acetylspermidine only in cysts. Acetylputrescine was present in both stages of two isolates but only in the growing amoebae of the third isolate. Spermine was not detected in any of the isolates. S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) were present in growing amoebae but SAM was undetectable or barely detectable in cysts. SAH also decreased in concentration during encystation of two of the isolates to a level comparable to that of the other isolate. The developmental transition from growing amoebae to dormant cysts is characterized metabolically by a threshold adjustment in concentration of SAM, SAH and of the polyamines (esp., DAP and SPD). PMID- 2586496 TI - Is the ATP-dependent protection of lysosomes against osmotic lysis a function of the lysosomal proton pump. AB - Rat liver lysosomes have been used to characterize further the effects of ATP on lysosomal stability during incubation at 37 degrees C at hypo-osmolarity. As previously reported, when the osmotically-supporting solute is the salt of a strong base (K+), ATP protects against lysis during incubation. However, if the osmotically-supporting solute is the salt of a weak base, e.g. Tris HCl or NH4Cl, ATP actually promotes lysis during incubation. Thus, ATP can exert destabilizing as well as protective effects on lysosomes. The destabilizing effect is eliminated by protonophores. The protective effect in the presence of potassium salts is not eliminated by protonophores. Moreover, when incubation is in the presence of a salt of a weak base, protonophores actually cause an ATP-dependent protective effect to be established. The destabilizing effect occurs at 37 degrees C, but not at 0 degrees C. The Mg++-dependence of the destabilizing effect was found to be similar to that found earlier for the ATP-dependent protective effect, insofar as only 1 mM MgCl2 in the presence of 1mM EDTA is sufficient for nearly maximal stimulation of both effects. The destabilizing effect may result from a H+ ion gradient across the lysosomal membrane which is maintained by the lysosomal ATP-dependent proton pump. The protective effect, on the other hand, does not depend on such a gradient being maintained; on the contrary, protonophores appear to act as enablers of the protective effect. The question that remains to be answered is: does the protective effect derive in some way from the same ATP-driven mechanism which constitutes the proton pump? Some possible answers to this question are considered. PMID- 2586497 TI - Beta globin gene transcripts originating in the promoter region during early hexamethylene bisacetamide and dimethylsulfoxide induction of Friend erythroleukemia cells. AB - The beta-globin transcripts which are induced by dimethylsulfoxide (DMSO) and hexamethylene bisacetamide (HMBA) have been characterized in order to assess potential differences in their mechanisms of induction. Transcripts which initiate in the 5' flanking promoter region are likely indicators of promoter accessibility and were therefore characterized during the time course of induction with each inducer in Friend Erythroleukemia cells. S1 analysis with probes labeled at - 12 or +82 relative to the (+1) cap site showed no major differences between 5' ends of the upstream initiated transcripts in cells induced by DMSO or HMBA. We detected several upstream bands with each inducer corresponding to beta-globin transcripts with 5' ends between - 190 and -55 relative to the cap site and found that cells induced with DMSO and HMBA show a similar transcription response as measured by initiation in the 5' flanking region of the beta-globin gene. Interestingly, the upstream initiated transcripts reach their peak concentration levels much earlier in the time course of induction than do the mRNA transcripts with 5' ends at the major (+1) cap site. Northern blot analysis detected the upstream initiated transcripts as early as 16 hours after induction with DMSO, primarily in unprocessed large transcripts. We find that the promoter region containing transcripts constitute a higher percent of total beta-globin transcripts at the start of the induction and may therefore have an early function in the multistep induction process. PMID- 2586498 TI - [Structuro-functional organization of segments of Co1A plasmid DNA, determining its stable inheritance]. AB - Two par regions were localized within the structure of a small colicinogenic plasmid ColA. One of them functions at the expense of plasmid multimere resolution. Analysis of the nucleotide sequence of the region revealed the existence of essential homology with the par locus of plasmid ColE1. As compared to E. coli C600, the function of multimere forms' resolution of plasmid DNA in E. coli C is reduced or absent due to par regions of the ColE1 type. Par regions of various degrees of homology with the par locus of ColE1 were localized by Southern hybridization within the structure of colicinogenic plasmids ColN and ColD. The stabilization of the colicinogenic plasmids is believed to be also determined by the functioning of genes connected with the synthesis and action of colicin. PMID- 2586499 TI - [Characteristic of segments of transgenic animal genomes, adjacent to integrated sequences of foreign DNA]. AB - DNAs of seven transgenic mice and one transgenic rabbit was divided into fractions according to reassociation kinetics and GC-content. Moderate and/or frequent (reverse) repeated sequences of the genome were revealed in all cases next to different transgenes. DNA fractions containing foreign sequences differed by the GC-content in different transgenic animals. PMID- 2586500 TI - [Determination of the substrate specificity of Bpu101 restrictase with an unusual recognition segment]. AB - A new enzyme Bpu10I was isolated from Bacillus pumilus. This enzyme is not an isoschizomer of any known restriction endonucleases. The search of possible recognition sequences was carried out in sequences ABCNiDEF (i = 0.6) on substrate DNA lambda CI857, T7, pBR322. The recognition sequence and cleavage sites of restriction endonuclease Bpu10I have been determined as CCTNAGC. GGANTCG PMID- 2586501 TI - [Primary structure of RNA 3 of barley stripe mosaic virus and its variability]. AB - The complete nucleotide sequence was determined for three variants of the third genomic component of BSMV strain Argentina mild. The common variant, RNA 3 (2797 nucleotide), contains two open reading frames (ORFs) coding for two proteins with Mr of 74,229 (putative BSMV RNA polymerase) and Mr of 16,994. The second ORF is expressed from a subgenomic RNA. The extended variant RNA 3 differs from the common one only by the presence of a direct tandem repeat 351-363 nucleotides in length (with some variability) encompassing part of the leader sequence and the beginning of the first ORF. The resulting protein has a Mr of about 86,000. The defective variant, RNA 4, carries a deletion of 185 nucleotides in the 3'-end proximal part of the first ORF, which shortens the product to a Mr of 60,344. PMID- 2586502 TI - [Thyroglobulin gene expression in human thyroid cells in various types of thyroid pathology]. AB - Highly purified thyroglobulin mRNA was isolated from human nodal euthyroid goiter. Full length cDNA was synthesized from 33S RNA by using reverse transcriptase in the presence of human placenta ribonuclease inhibitor. DNA complementary to human Tg mRNA was used in liquid hybridization experiments to determine the quantity of Tg mRNA. The amount of Tg mRNA in euthyroid nodal and congenital goiter was reduced. Tg specific mRNA was absent in thyroid cancer cells. PMID- 2586503 TI - [ID-similar sequences in various types of DNA clones]. AB - The sequence of rat ID repeat was compared with those of Escherichia coli, Drosophila melanogaster, chicken, rat, mouse and human clones and clones with t RNA gene from EMBL-5 date bank. This comparison was made bearing on the determination of the level of mutual information between the sequences compared. The non-canonical similarity of the ID repeat sequence with the tRNA genes was found. It is revealed by the conservation of purine or pyrimidine sites in the sequences compared. In human and mouse clones purine-pyrimidine copies of rat ID sequence were also found. In some cases these sequences were flanked by short direct repeats, they contained also poly(A)-like sequences. The possible functional meaning and evolutional origin of the revealed relations are discussed. PMID- 2586504 TI - [The effect of cytisine on mRNA transport in the cytoplasm of eukaryotic cells (plants and animals)]. AB - The action of alkaloid cytisine on protein biosynthesis in eukaryotic cells was studied. It was shown that the alkaloid had no effect on mRNA translation. Cytisine inhibited the release of mRNP particles from rat liver and wheat embryos nuclei. Sedimentation properties and distribution in CsCl gradient of the material extracted from alkaloid-treated nuclei did not differ from control one and were similar to informosomes from animal and plant cells described earlier. The main part of mRNA with sedimentation coefficients 14-18S, capable for translation in the cytoplasm is retained in alkaloid-treated nuclei. PMID- 2586505 TI - [tRNA as a possible primer for the initiation of reverse transcription of dispersed repeats Alu, B1, B2 and L1]. AB - The contextual analysis of the primary structures of 28 various dispersed repeats Alu, B1, B2 and L1 (Kpn1) of primates and rodent genomes has been carried out to search for the regions complementary to the 3'-ends of the known at present tRNA of these organisms. It has been shown that the abundance of the investigated repeats contain the regions revealing marked and statistically non-random complementarity to the 3'-end of at least one of the tRNA considered. Taking into account the retroviruses replication model known from literature these revealed regions are considered as potential primer-binding sites for the initiation of reverse transcription of the mentioned repeats or more long DNA fragments containing them. PMID- 2586506 TI - [Participation of small RNAs, associated with poly(A)+RNA in cytoplasm in hormonal regulation of genome expression]. AB - The fraction of small RNA (sacc-RNA), associated with cytoplasmic rat liver poly(A)+RNA by non-covalent, possibly complementary interactions, has been isolated and studied. Fingerprint analysis data reveal that the specific changes occur in the population of sacc-RNA in response to glucocorticoid treatment. The close similarity of oligonucleotide composition of sacc-RNA and RNA-component of small nuclear RNP-acceptor of glucocorticoid hormones has been found. The tightly boynd peptides were observed in the fraction of sacc-RNA. The hypothesis of the involvement of the small RNA in the hormonal regulation at post-transcriptional stages of gene expression in the cytoplasm has been forward. PMID- 2586507 TI - [Parallel DNA double helices. II. Conformational analysis of regular helices having a second order axis of symmetry]. AB - Conformational analysis of double helices of DNA with parallel arranged sugar phosphate chains connected by twofold symmetry has been performed. Homopolymers poly(dA).poly(dA), poly(dC).poly(dC), poly(dG).poly(dG) and poly(dT).poly(dT) were studied. For each of the homopolymers all variants of H-bond pairing were checked. The maps of closing of sugar-phosphate backbone were previously computed. By the optimization of potential energy the dihedral angles and helix parameters of relatively stable conformations of parallel stranded polynucleotides were calculated. The dependence of conformational energy on the nucleic base character and the base pair type were studied. Two main conformational regions for favourable "parallel" helix of polynucleotides were found. The former of these two regions coincide with the region of typical conformational parameters of B-DNA. On an average the conformational energy of "parallel" DNA is close to the energy of canonic "antiparallel" B-DNA. PMID- 2586508 TI - [Use of phase diagrams in crystallization of oligonucleotide duplexes. II. Setting of the crystallized samples]. AB - Oligonucleotide crystallization technique based on the method of phase diagrams is described in detail with (pGpT)3.(pApC)3 hexamer as an example. The key point of the technique consists of dividing the multiparameter crystallization space into a set of regions, each of which corresponds to the precipitation of a duplex in complex with a certain number of counterions. PMID- 2586509 TI - [Characteristics of DNA isolated from a complex form of DNA-polymerase alpha from the rat liver]. AB - A complex from of DNA polymerase alpha was isolated from the nuclear membrane of hepatocytes. DNA fragments were shown to be among components of the complex under study. In this paper we present evidence that DNA from the alpha-polymerase complex from quiescent hepatocytes (DNA-G) differs in its nucleotide composition from its counterpart (DNA-S) isolated from hepatocytes synthesizing DNA. As judged by dot hybridization, DNA-G0 does not contain nucleotide sequences which are complementary to ribosomal or messenger RNA, whereas the abovementioned sequences are present in DNA-S. At the same time DNA-G0 is found to contain sequences which are homologous to both SV40 DNA and yeast TRPI-ARS1 DNA. The difference in nucleotide sequences between DNA-G0 and DNA-S indicates that in the process of replication DNA is being stretched across the multienzyme complex located on the nuclear membrane. PMID- 2586510 TI - [A study of the molecular mechanism of DNA interaction with divalent metal ions]. AB - The interaction of DNA with divalent metal ions: Ba2+, Mg2+, Mn2+, Ni2+, Cu2+ in solutions at different ionic strengths mu was investigated. The combination of following methods: flow birefringence, viscometry, UV-spectroscopy and circular dichroism made possible to follow the state of the secondary and tertiary structure of the DNA molecule during its interaction with ions. The presence of divalent ions in solution affects the hydrodynamic properties of DNA only at low mu. At high mu the difference in the action of mono- and divalent ions disappears. The persistence length of DNA does not change during the experiment. It is shown that the Mg2+ and Ba2+ ions interact only with phosphate groups of DNA but Mn2+, Ni2+, Cu2+ ions interact also with the nitrogen bases of the macromolecule. PMID- 2586511 TI - [Inhibition of replication of human hepatitis B virus]. AB - Several nucleoside 5'-triphosphate analogs were investigated as inhibitors of human hepatitis B virus replication. Different analogs inhibited DNA synthesis differently, 3'-azido-2',3'-dideoxythymidine 5'triphosphate being the most active compound. This inhibitor blocked DNA synthesis by 50% at inhibitor: substrate molar ratio 1:8, and by 80% - at 1:1. The hypothesis is formulated that 3'-azido 2',3'-dideoxythymidine 5'-triphosphate inhibits RNA directed viral DNA replication due to incorporation of this compound into 3'-termini of newly synthesized DNA chains. The phenomenon observed opens new possibilities for chemotherapy of acute and chronic human hepatitis B. PMID- 2586512 TI - [Characteristics of a frequently repetitive sequence family in the bull genome]. AB - The repeated sequences situated in 5'- and 3'-flanking regions of the bovine growth hormone gene were cloned and characterized. It was shown that they are related to a described before PstI-family of bovine repeats with a frequency of repetition about 10(5). PstI-repeats are found only in genomes of sheep and goats subfamily (Carpinae) and not found in DNA of other analysed vertebrate species. Repeats of this family are situated in the genome as a number of dispersed clusters, they have conservative structure and are alike by the frequency of repetition in the DNA of all organisms that contain them. The presence of sequences homologous to PstI-repeats are shown in bovine pituitary poly(A)+ cytoplasmic RNA by means of North-hybridization. PMID- 2586514 TI - Novel regulation of transcription initiation of the peptide IX gene of adenovirus 2. AB - cis-Acting elements involved in transcription of the peptide IX (pIX) gene of adenovirus 2 were identified by using in vivo transient expression assays and two in vitro transcription systems. Deletion of either the sequence between positions -45 and -70 or the TATA box abolished the initiation of pIX gene transcription in vivo and transcription with HeLa cell nuclear extracts in vitro. These results initially suggested the presence of a positive factor acting on the upstream element. However, when proteins in the nuclear extract were fractionated by column chromatography and analyzed by reconstitution of transcription in vitro, it was found that a certain fraction could direct TATA box-dependent transcription initiation even in the absence of the upstream element. Furthermore, activity inhibiting TATA box-dependent transcription was found in the nuclear extract. In contrast, inhibition of TATA box-dependent transcription was suppressed by deletion of a downstream sequence between positions +33 and +122. These results indicate that the TATA box of the pIX gene by itself has the ability to direct initiation of constitutive transcription but that the function of this element is under negative control by a repressor acting on a downstream sequence. Thus, the upstream element of the pIX gene appears to have a novel function: suppression of the transcriptional repression exerted by a downstream sequence, leading to a net transcription activation. Possible mechanisms for transcription initiation of pIX DNA are discussed. PMID- 2586515 TI - Microinjection of plasmid DNA encoding the A surface antigen of Paramecium tetraurelia restores the ability to regenerate a wild-type macronucleus. AB - Strain d48 of Paramecium tetraurelia contains the A i-antigen gene in the micronucleus, but the gene is lost when micronuclear products develop into the macronucleus. It has recently been shown that when injected into d48, macronucleoplasm from the wild type transforms d48 cells to wild type. It is shown here that wild-type cytoplasm can also bring about transformation, with a marked stage-specific sensitivity for both donor and recipient. It was also found that a plasmid containing the cloned A gene could transform d48 to wild type. Injection of nucleoplasm from animals in the vegetative stage of the cell cycle into the cytoplasm of recipients at various stages of autogamy caused high frequency transformation of cells able to express the A serotype both before and after the next autogamy. Injection of nucleoplasm into vegetative macronuclei produced over 70% transformants able to express the A serotype after the next autogamy. The ability of nucleoplasm to transform was acquired at the second cell cycle after autogamy and was maintained throughout the vegetative stage. When cytoplasm was obtained from donors during autogamy and injected into the cytoplasm of recipients 1 to 2 h after the sensitive period, quite high frequencies of stable revertants were found when tested both before and after the next autogamy. Cells that were injected into the macronucleus with the cloned A plasmid expressed the A serotype after five fissions in over 20% of the lines and maintained this ability through successive fissions; all transformants except one stably expressed the A serotype even after the next autogamy. PMID- 2586513 TI - Molecular cloning and sequencing of ama-1, the gene encoding the largest subunit of Caenorhabditis elegans RNA polymerase II. AB - Two genomic sequences that share homology with Rp11215, the gene encoding the largest subunit of RNA polymerase II in Drosophila melanogaster, have been isolated from the nematode Caenorhabditis elegans. One of these sequences was physically mapped on chromosome IV within a region deleted by the deficiency mDf4, 25 kilobases (kb) from the left deficiency breakpoint. This position corresponds to ama-1 (resistance to alpha-amanitin), a gene shown previously to encode a subunit of RNA polymerase II. Northern (RNA) blotting and DNA sequencing revealed that ama-1 spans 10 kb, is punctuated by 11 introns, and encodes a 5.9 kb mRNA. A cDNA clone was isolated and partially sequenced to confirm the 3' end and several splice junctions. Analysis of the inferred 1,859-residue ama-1 product showed considerable identity with the largest subunit of RNAP II from other organisms, including the presence of a zinc finger motif near the amino terminus, and a carboxyl-terminal domain of 42 tandemly reiterated heptamers with the consensus Tyr Ser Pro Thr Ser Pro Ser. The latter domain was found to be encoded by four exons. In addition, the sequence oriented ama-1 transcription with respect to the genetic map. The second C. elegans sequence detected with the Drosophila probe, named rpc-1, was found to encode a 4.8-kb transcript and hybridized strongly to the gene encoding the largest subunit of RNA polymerase III from yeast, implicating rpc-1 as encoding the analogous peptide in the nematode. By contrast with ama-1, rpc-1 was not deleted by mDf4 or larger deficiencies examined, indicating that these genes are no closer than 150 kb. Genes flanking ama-1, including two collagen genes, also have been identified. PMID- 2586516 TI - Analysis by cell-free transcription of the liver-specific pyruvate kinase gene promoter. AB - A DNA fragment spanning nucleotides -183 to -4 with respect to the cap site of the rat L-type pyruvate kinase (L-PK) gene contains at least four binding sites for putative transcriptional factors: hepatocyte nuclear factor 1 (HNF1), liver factor A1 (LF-A1), nuclear factor 1 (NF1), and major late transcription factor (MLTF). This fragment was used to direct transcription of a reporter sequence (a G-free cassette) in cell extracts. This L-PK promoter was active in liver nuclear extracts, but not in extracts from nonhepatic tissues. A reduction of 50% of the activity was obtained with a deleted L-PK promoter containing only the HNF1 binding site. In contrast, deletion of the HNF1-binding site inactivated the promoter by more than 90%. These results were confirmed by titration experiments with synthetic oligonucleotides. Titration of HNF1 resulted in an 85% decrease of transcriptional activity, while titration of LF-A1 resulted in only a 40% decrease. The influence of NF1 and MLTF seemed to be marginal in this system. The proximal 5'-flanking sequence of the L-PK gene therefore appears to function in vitro as an efficient liver-specific promoter which requires the binding of the liver factor HNF1 and which is also stimulated by the binding of another liver specific factor, LF-A1. PMID- 2586517 TI - Accurate processing of human pre-rRNA in vitro. AB - We report here that the mature 5' terminus of human 18S rRNA is generated in vitro by a two-step processing reaction. In the first step, SP6 transcripts were specifically cleaved in HeLa cell nucleolar extract at three positions near the external transcribed spacer (ETS)-18S boundary. Of these cleavage sites, two were major and the other was minor. RNase T1 fingerprint and secondary nuclease analyses placed the two major cleavage sites 3 and 8 bases upstream from the mature 5' end of 18S rRNA and the minor cleavage site 1 base into the 18S sequence. All three cleavages yielded 5'-hydroxyl, 2'-3'-cyclic phosphate termini and were 5' of adenosine residues in the sequence UACCU, which was repeated three times near the ETS-18S boundary. In the second step, the initial cleavage product containing 3 bases of ETS was converted to an RNA with a 5' terminus identical to that of mature 18S RNA by an activity found in HeLa cell cytoplasmic extracts. PMID- 2586519 TI - Subcellular localization of an intermediate filament protein and its mRNA in glial cells. AB - Eucaryotic mRNAs are generally localized in the cell body, where most protein synthesis occurs. We have found that mRNAs encoding the glial intermediate filament protein are spatially distributed in the glial cell cytoplasm close to the location of the glial filaments. Whereas the glial filament protein mRNA was located predominantly in the distal process, actin mRNA was found almost exclusively in the apical portion of the glial cell. This pattern of mRNA localization might provide a mechanism for synthesis of proteins in specific subcellular compartments by mRNA translation locally. PMID- 2586518 TI - Novel N-terminal amino acid sequence required for retention of a hepatitis B virus glycoprotein in the endoplasmic reticulum. AB - The preS1 surface glycoprotein of hepatitis B virus is targeted to the endoplasmic reticulum (ER) and is retained in this organelle when expressed in the absence of other viral gene products. The protein is also acylated at its N terminus with myristic acid. Sequences responsible for its ER retention have been identified through examination of mutants bearing lesions in the preS1 coding region. These studies reveal that such sequences map to the N terminus of the molecule, between residues 6 and 19. Molecules in which this region was present remained in the ER; those in which it had been deleted were secreted from the cell. Although all deletions which allowed efficient secretion also impaired acylation of the polypeptide, myristylation alone was not sufficient for ER retention: point mutations which eliminated myristylation did not lead to secretion. These data indicate that an essential element for ER retention resides in a 14-amino-acid sequence that is unrelated to previously described ER retention signals. PMID- 2586520 TI - Developmental expression and 5S rRNA-binding activity of Xenopus laevis ribosomal protein L5. AB - Ribosomal protein L5 binds specifically to 5S rRNA to form a complex that is a precursor to 60S subunit assembly in vivo. Analyses in yeast cells, mammalian cells, and Xenopus embryos have shown that the accumulation of L5 is not coordinated with the expression of other ribosomal proteins. In this study, the primary structure and developmental expression of Xenopus ribosomal protein L5 were examined to determine the basis for its distinct regulation. These analyses showed that L5 expression could either coincide with 5S rRNA synthesis and ribosome assembly or be controlled independently of these events at different stages of Xenopus development. L5 synthesis during oogenesis was uncoupled from the accumulation of 5S rRNa but coincided with subunit assembly. In early embryos, the inefficient translation of L5 mRNA resulted in the accumulation of a stable L5-5S rRNA complex before ribosome assembly at later stages of development. Additional results demonstrated that L5 protein synthesized in vitro bound specifically to 5S rRNA. PMID- 2586521 TI - Glucocorticoid receptor binding to a specific DNA sequence is required for hormone-dependent repression of pro-opiomelanocortin gene transcription. AB - Glucocorticoids rapidly and specifically inhibit transcription of the pro opiomelanocortin (POMC) gene in the anterior pituitary, thus offering a model for studying negative control of transcription in mammals. We have defined an element within the rat POMC gene 5'-flanking region that is required for glucocorticoid inhibition of POMC gene transcription in POMC-expressing pituitary tumor cells (AtT-20). This element contains an in vitro binding site for purified glucocorticoid receptor. Site-directed mutagenesis revealed that binding of the receptor to this site located at position base pair -63 is essential for glucocorticoid repression of transcription. Although related to the well-defined glucocorticoid response element (GRE) found in glucocorticoid-inducible genes, the DNA sequence of the POMC negative glucocorticoid response element (nGRE) differs significantly from the GRE consensus; this sequence divergence may result in different receptor-DNA interactions and may account at least in part for the opposite transcriptional properties of these elements. Hormone-dependent repression of POMC gene transcription may be due to binding of the receptor over a positive regulatory element of the promoter. Thus, repression may result from mutually exclusive binding of two DNA-binding proteins to overlapping DNA sequences. PMID- 2586522 TI - Transcription factor MBF-I interacts with metal regulatory elements of higher eucaryotic metallothionein genes. AB - Metallothionein (MT) gene promoters in higher eucaryotes contain multiple metal regulatory elements (MREs) that are responsible for the metal induction of MT gene transcription. We identified and purified to near homogeneity a 74 kilodalton mouse nuclear protein that specifically binds to certain MRE sequences. This protein, MBF-I, was purified employing as an affinity reagent a trout MRE that is shown to be functional in mouse cells but which lacks the G+C rich and SP1-like sequences found in many mammalian MT gene promoters. Using point-mutated MREs, we showed that there is a strong correlation between DNA binding in vitro and MT gene regulation in vivo, suggesting a direct role of MBF I in MT gene transcription. We also showed that MBF-I can induce MT gene transcription in vitro in a mouse extract and that this stimulation requires zinc. PMID- 2586523 TI - Different regions of the estrogen receptor are required for synergistic action with the glucocorticoid and progesterone receptors. AB - Estrogen and progesterone or estrogen and glucocorticoid receptors functionally cooperate in gene activation if their cognate binding sites are close to one another. These interactions have been described as synergism of action of the steroid receptors. The mechanism by which synergism is achieved is not clear, although protein-protein interaction of the receptors is one of the favorite models. In transfection experiments with receptor expression vectors and a reporter gene containing estrogen and progesterone-glucocorticoid receptor binding sites, we have examined the effects that different portions of the various receptors have on synergism. N-terminal domains of the chicken progesterone and human glucocorticoid receptors, when deleted, abolished the synergistic action of these receptors with the estrogen receptor. Deletion of the carboxy-terminal amino acids 341 to 595 of the estrogen receptor produced a mutant receptor that could not trans-activate on its own. This mutant receptor did not affect the action of the glucocorticoid receptor but functioned synergistically with the progesterone receptor. We therefore conclude that the synergistic action of the receptors for estrogen and progesterone is mechanistically different from the synergistic action of the receptors for estrogen and glucocorticoid. PMID- 2586524 TI - Structure of an ectodermally expressed sea urchin metallothionein gene and characterization of its metal-responsive region. AB - The metallothionein-A gene in the metallothionein gene family of the sea urchin Strongylocentrotus purpuratus (SpMTA gene) was sequenced and found to contain three coding exons plus a 3' entirely noncoding exon. Putative alpha and beta MT domains were encoded, by its exons 2 and 3, respectively, in reverse of the order in vertebrate metallothionein genes. The SpMTA promoter was characterized through the expression of recombinant constructs containing various portions of the proximal 678-base-pair (bp) 5'-flanking region of the SpMTA gene. Zygotes injected with constructs were cultured to the blastula stage in the presence of a heavy-metal chelator and then incubated in the presence or absence of cadmium. The longest constructs were expressed only when heavy-metal ion was present. Two putative metal-responsive elements (MREs a and b) within 240 bp of the transcription start site resembled mammalian MREs in their critical 8-bp cores (TGCRCNCS) and in their locations relative to each other and to the TATA box. Elimination of activity by site-specific mutations in MREs a and b, separately or in both, identified them as metal regulatory elements. Thus, MRE recognition in this invertebrate resembles that in vertebrates. Upstream sites with single mismatched MREs neither acted as MREs nor amplified the activity of MREs a and b. The SpMTA, Spec1, and CyIIIa actin genes, which have the same ectodermal specificity, have common DNA elements at relatively similar locations in their promoter regions; however, these elements are insufficient in themselves to promote gene expression. PMID- 2586525 TI - Complex regulation of transforming growth factor beta 1, beta 2, and beta 3 mRNA expression in mouse fibroblasts and keratinocytes by transforming growth factors beta 1 and beta 2. AB - Regulation of transforming growth factor beta 1 (TGF beta 1), TGF beta 2, and TGF beta 3 mRNAs in murine fibroblasts and keratinocytes by TGF beta 1 and TGF beta 2 was studied. In quiescent AKR-2B fibroblasts, in which TGF beta induces delayed stimulation of DNA synthesis, TGF beta 1 autoregulation of TGF beta 1 expression was observed as early as 1 h, with maximal induction (25-fold) after 6 to 12 h. Increased expression of TGF beta 1 mRNA was accompanied by increased TGF beta protein production into conditioned medium of AKR-2B cells. Neither TGF beta 2 nor TGF beta 3 mRNA, however, was significantly induced, but both were apparently down regulated at later times by TGF beta 1. Protein synthesis was not required for autoinduction of TGF beta 1 mRNA in AKR-2B cells. Nuclear run-on analyses and dactinomycin experiments indicated that autoregulation of TGF beta 1 expression is complex, involving both increased transcription and message stabilization. In contrast to TGF beta 1, TGF beta 2 treatment of quiescent AKR-2B cells increased expression of TGF beta 1, TGF beta 2, and TGF beta 3 mRNAs, but with different kinetics. Autoinduction of TGF beta 2 mRNA occurred rapidly with maximal induction at 1 to 3 h, enhanced TGF beta 3 mRNA levels were observed after 3 h, and increased expression of TGF beta 1 occurred later, with maximal mRNA levels obtained after 12 to 24 h. Nuclear run-on analyses indicated that TGF beta 2 regulation of TGF beta 2 and TGF beta 3 mRNA levels is transcriptional, while TGF beta 2 induction of TGF beta 1 expression most likely involves both transcriptional and posttranscriptional controls. In BALB/MK mouse keratinocytes, minimal autoinduction of TGF beta 1 occurred at only the 12- and 24-h time points and protein synthesis was required for this autoinduction. The results of this study provide an example in which TGF beta 1 and TGF beta 2 elicit different responses and demonstrate that expression of TGF beta 1, and TGF beta 3 are regulated differently. The physiological relevance of TGF beta 1 autoinduction in the context of wound healing is discussed. PMID- 2586526 TI - A nuclear factor I-like activity and a liver-specific repressor govern estrogen regulated in vitro transcription from the Xenopus laevis vitellogenin B1 promoter. AB - A hormone-controlled in vitro transcription system derived from Xenopus liver nuclear extracts was exploited to identify novel cis-acting elements within the vitellogenin gene B1 promoter region. In addition to the already well-documented estrogen-responsive element (ERE), two elements were found within the 140 base pairs upstream of the transcription initiation site. One of them, a negative regulatory element, is responsible for the lack of promoter activity in the absence of the hormone and, as demonstrated by DNA-binding assays, interacts with a liver-specific transcription factor. The second is required in association with the estrogen-responsive element to mediate hormonal induction and is recognized by the Xenopus liver homolog of nuclear factor I. PMID- 2586527 TI - Histone H1 represses transcription from minichromosomes assembled in vitro. AB - We have previously shown that transcription from a Xenopus 5S rRNA gene assembled into chromatin in vitro can be repressed in the absence of histone H1 at high nucleosome densities (one nucleosome per 160 base pairs of DNA) (A. Shimamura, D. Tremethick, and A. Worcel, Mol. Cell. Biol. 8:4257-4269, 1988). We report here that transcriptional repression may also be achieved at lower nucleosome densities (one nucleosome per 215 base pairs of DNA) when histone H1 is present. Removal of histone H1 from the minichromosomes with Biorex under conditions in which no nucleosome disruption was observed led to transcriptional activation. Transcriptional repression could be restored by adding histone H1 back to the H1 depleted minichromosomes. The levels of histone H1 that repressed the H1-depleted minichromosomes failed to repress transcription from free DNA templates present in trans. The assembly of transcription complexes onto the H1-depleted minichromosomes protected the 5S RNA gene from inactivation by histone H1. PMID- 2586528 TI - Characterization of the Schizosaccharomyces pombe ral2 gene implicated in activation of the ras1 gene product. AB - Mutations in the Schizosaccharomyces pombe ral2 gene cause a phenotype indistinguishable from that of the ras1-defective mutant. Using cloned ral2 DNA, we disrupted the chromosomal gene. The disruptants showed the same phenotype as the original ral2 isolates, i.e., they had spherical cells, had no detectable mating activity, and exhibited no response to the mating pheromone, but their vegetative growth was apparently normal. Sequence analysis of the ral2 gene suggests that it encodes a polypeptide of 611 amino acid residues whose predicted amino acid sequence shows no strong homology to any known protein. Either multiple copies or even a single copy of the ras1Val-17 allele, which is an activated form of ras1, restored rodlike cell morphology and ability to respond to the mating factor to ral2 mutants. These results suggest that the ral2 and ras1 gene products interact intimately and that the ral2 gene product is involved in activation of the ras1 protein in S. pombe. PMID- 2586529 TI - In vitro analysis of the pea chloroplast 16S rRNA gene promoter. AB - A cloned pea chloroplast 16S rRNA gene promoter has been characterized in detail by use of a homologous in vitro transcription system that contains a highly purified chloroplast RNA polymerase. The in vivo and in vitro 16S rRNA transcriptional start site has been identified to be a T on the plus strand, 158 bases upstream of the mature 5' end of the gene. BAL 31 deletions of the 16S rRNA leader region demonstrated that the bases between -66 to +30 relative to the transcriptional start site (+1) are necessary for specific 16S transcription. Disruption of canonical TTGACA or TATAAT elements within this region caused complete transcriptional inactivation and prevented protein binding. The topological requirement for 16S transcription was examined by using a construct that synthesized a transcript from the 16S promoter and released it from a pea plastid putative terminator sequence. This minigene was relaxed in vitro with a topoisomerase I from pea chloroplast. It was shown that the 16S promoter was most active when the minigene plasmid was supercoiled. PMID- 2586532 TI - [Tumor cytogenetics and prognosis in neuroblastoma]. AB - In 40 children with neuroblastoma of different clinical stages the tumorkaryotype was determined at onset (n = 30) or at relapse (n = 10) of disease after short term culture of tumor tissues or bone marrow aspirates. None of the 10 stage I, II, and IVs tumors revealed a chromosome 1p aberration, in contrast to stage III and IV tumors where this abnormality was encountered in 25 (=83%) of 30 patients. Amplification of the proto-oncogene N-myc in the tumor-DNA could not be detected in stage I, II and IVs, was however present in 53% of stage III and IV tumors. Cytogenetic phenomena of gene amplification such as Double minutes (DMs) and Homogeneously Staining Regions (HSRs) correlated with N-myc amplification. About 50% of stage III and IV tumors had chromosome numbers in the neardiploid range whereas prognostically favourable tumors were characterized by hyperploid chromosomal numbers mainly in the triploid range. Life-table analysis according to Kaplan-Meier showed a probability of surviving in about 80% of patients with a normal morphology of chromosome 1 in their tumor cells, compared to about 60% in the absence of N-myc oncogene amplification and of about 50%, if aneuploidy is detected. Thus, we think, the presence or absence of chromosome 1p aberration in the tumorkaryotype is the most sensitive discriminator for outcome in children with neuroblastoma. PMID- 2586531 TI - [Intellectual development of phenylketonuria children treated early--a longitudinal study. 10 years' concomitant psychological study in The Netherlands]. AB - Since 1st September 1974 almost all newborns in The Netherlands have been screened for phenylketonuria (PKU). Data collected between then and 1 October 1984 are presented, with respect to the intellectual functioning of 69 patients who received early treatment for PKU. Wherever possible, psychological testing was carried out at four key ages, namely 1.0 years, 2.0 years, 4.6 years, 6.6 years. The results of the tests revealed no differences in the mental levels of these patients and healthy children at any of the key ages. Also no sex differences at key ages 1 and 2 years related to this variable were found. The longitudinal course of the intellectual development in the first four and a half years was stable. The necessity for the continuation of screening and the collection of psychosocial data is discussed. PMID- 2586530 TI - Rates of mutation to growth factor autonomy and tumorigenicity differ in hematopoietic stem and precursor cells expressing the multilineage colony stimulating factor gene. AB - At least two separate but interdependent events are required to attain autonomous growth as a consequence of ectopic expression of the multilineage colony stimulating factor gene in hematopoietic progenitor cells. The rate at which the second event occurs is more than 3 orders of magnitude higher in precursor cell lines (FDC-P1 or FDC-P2) than in stem cell lines (FDC-Pmix). Autonomous, but not density-dependent, growth is tightly coupled to tumorigenicity in precursor cells; however, neither growth-factor-independent nor autonomously growing stem cell lines are tumorigenic. PMID- 2586533 TI - [Nursery schools, a site for exposure to house dust mite allergens?]. AB - In June 1988, 110 dust samples from carpets, cushions, mattresses and upholstered furniture were collected by vacuum cleaner in 33 municipal nursery schools. All samples were assessed with guanine test strips (Acarex). In all samples giving moderately or strongly positive results in these tests (guanine stages 2 and 3) and in 10 random samples each from of stages 1 (weakly positive) and 0 (negative), mites were counted by light microscope. In 36% of the nursery schools, objects with guanine stages 2 or 3 were found, which indicates a high allergen burden. The high guanine stages were found only in mattresses, cushions and upholstered furniture. Nursery schools can be source areas of significant allergen exposure relevant for children with dust mite allergies. PMID- 2586534 TI - [Follow-up of perinatal HIV infection]. AB - The clinical course of a perinatal HIV infection in a 3 1/2-year-old girl is presented. The girl became HIV-positive at the age of 6 months, at about the same time as her mother. She is receiving continuous prophylactic treatment with immunoglobulins and cotrimoxazol. The pathological findings and the stage according to the classification of the Centers for Disease Control are discussed. PMID- 2586536 TI - [1st SKD Vaccine Forum. 28 April-1 May 1989, Marbella (Spain)]. PMID- 2586535 TI - [Hypoglycemia and cholestatic jaundice in congenital panhypopituitarism]. AB - The case of a female newborn who was first found to have severe recurrent hypoglycemia and then developed cholestasis with conjugated hyperbilirubinemia is presented. No infectious diseases, metabolic defects, or disease of the hepatobiliary system were found. Endocrinological investigations revealed panhypopituitarism. Hypoplasia or aplasia of the pituitary was suspected. Cholestasis and hyperbilirubinemia must be seen in association with growth hormone and cortisol deficiency in the context of pathogenesis. PMID- 2586537 TI - The impact of molecular biology on understanding of the human disease process. PMID- 2586540 TI - Installation of fifth president of the Mount Sinai Medical Center December 6, 1988. Inaugural address. PMID- 2586538 TI - The gift of life: dilemmas in organ transplantation. PMID- 2586539 TI - The quest for quality health care: whose choice? Whose responsibility? PMID- 2586541 TI - Effects of theophylline on chromosomal breakage and sister-chromatid exchange. AB - Frequencies of both sister-chromatid exchange (SCE) and chromosomal breakage (CB) were studied in the lymphocytes of normal individuals (10 and 7 individuals respectively). The cells were exposed in vitro to 3 different concentrations of theophylline (1, 10 and 100 micrograms/ml). A significant concentration effect of the drug was demonstrated for both SCEs and CB. Utilizing a Dunnett's test for individual comparisons, the 10 and 100 micrograms/ml concentrations both demonstrated a significant elevation of SCEs and CB compared to the untreated control cultures. This study suggests that in vitro concentrations of theophylline equal to or greater than 10 micrograms/ml, corresponding to serum levels attained during therapy, increase the frequency of SCEs and chromosome breakage in human lymphocytes. PMID- 2586542 TI - Clastogenicity evaluation of seven chemicals commonly found at hazardous industrial waste sites. AB - 7 chemicals commonly found at the industrial waste sites were tested with the Tradescantia-Micronucleus (Trad-MCN) assay to evaluate their clastogenic potential. Chemicals selected from the US EPA Superfund Priority 1 list were: aldrin, arsenic trioxide, 1,2-benz[a, h]anthracene, dieldrin, heptachlor, lead tetraacetate and tetrachloroethylene. Results of repeated tests for clastogenicity yielded the minimum effective dose (MED) for clastogenicity of 0.44 ppm for lead tetraacetate, 1.88 ppm for heptaclor, 3.81 ppm for dieldrin and arsenic trioxide and 1,2-benz[a, h]anthracene yielded positive responses at the MED of 3.96 ppm and 12.50 ppm respectively. Aldrin and tetrachloroethylene were considered to be immiscible with water, and the tests yielded negative responses. Tetrachloroethylene in gaseous state was also used to treat the flower buds. Results of tetrachloroethylene vapor phase treatment yielded a positive response at the MED of 30 ppm/min after a 2-h exposure. 5 chemicals determined to be clastogens by this test were ranked according to their MED in the descending order of potency as follows: lead tetraacetate, heptachlor, dieldrin, arsenic trioxide and 1,2-benz[a, h]anthracene. Results of this study indicate that the Trad-MCN bioassay could be effectively utilized for assessing the potential clastogenicity of the chemicals commonly found at the industrial hazardous waste sites. PMID- 2586543 TI - Quantification of unscheduled DNA synthesis by a whole cell counting method. AB - A procedure was developed for the quantification of the autoradiographic assay for unscheduled DNA synthesis. Relative to commonly used practices for grain counting, this procedure provides a more accurate net nuclear grain count by eliminating the subjectivity currently associated with selection of the areas to be counted for the cytoplasmic background count. Briefly, the object area and aperture area modes of an ARTEK 880 colony counter are used to collect values for the total number of silver grains over a particular cell (nuclear and cytoplasmic counts), as well as for the nuclear and cytoplasmic areas. These values are then employed in a short algorithm to determine the net nuclear grain count. This new method provides greater sensitivity for defining weak UDS responses and the data collected readily lends itself to statistical analysis. PMID- 2586544 TI - Sister-chromatid exchange studies on direct- and indirect-acting clastogens in mouse primary cell cultures. AB - An in vitro sister-chromatid exchange (SCE) assay using mouse primary bone marrow and spleen cells was conducted with both direct- and indirect-acting genotoxic agents. 2,4,7-Trinitrofluorenone, a direct-acting genotoxic agent, induced a significant dose-related increase in SCEs. In both bone marrow and spleen cells, 2.0 micrograms/ml caused an approx. 3-fold increase in SCE level over control values. Cyclophosphamide, an indirect-acting genotoxicant which requires metabolic activation for its clastogenicity, induced a significant increase in SCEs in the presence of S9 from liver of rats pretreated with Aroclor-1254. A dose of 2 micrograms/ml resulted in a 2-fold increase in bone marrow and a greater than 5-fold increase in spleen cells. Benzo[a]pyrene, another indirect acting genotoxicant, also induced significant dose-related SCE responses in both cell types. It seems that primary bone marrow and spleen cell culture systems can detect both direct- and indirect-acting genotoxicants and may be useful for routine and/or comparative cytogenetic studies. PMID- 2586545 TI - Interlaboratory comparison of the 32P-postlabelling assay for aromatic DNA adducts in white blood cells of iron foundry workers. AB - Analysis by nuclease P1-enhanced 32P-postlabelling assay of DNA isolated from the white blood cells of 53 iron foundry workers was carried out independently in 3 laboratories, and the presence of aromatic DNA adducts was detected. The mean adduct levels in foundry workers varied from 9.2 +/- 23 (laboratory 3) and 12 +/- 10 (laboratory 2) to 26 +/- 43 (laboratory 1) and for the controls from 1.7 +/- 0.7 (laboratory 3) to 3.1 +/- 1.7 (laboratory 1) adducts per 10(8) nucleotides. No effect of smoking was observed in the present study. Each laboratory observed large interindividual variations of adduct levels. Good correlations were found between the results of the 32P-postlabelling assays carried out in the 3 laboratories; the correlation coefficients between laboratories 1 and 2, 1 and 3, and 2 and 3 were 0.61, 0.62, and 0.45, respectively, all being statistically highly significant (p less than 0.01). This interlaboratory comparison of the 32P postlabelling method indicates the reproducibility of the method and its applicability in occupational exposure monitoring. PMID- 2586546 TI - Inhibition of clastogenic effect of radiation by Liv. 52 in the bone marrow of mice. AB - The frequency of micronuclei in bone marrow cells of mice treated or not with Liv. 52 and then exposed to 4.5 Gy of gamma-radiation was evaluated from 6 h to 14 days post irradiation. The frequency of micronuclei increased from 6 h to 24 h post irradiated in both irradiated groups and declined thereafter, the frequency of micronuclei remaining significantly lower in the Liv. 52-treated group. These data demonstrate that Liv. 52 protects the bone marrow of mice against radiation injury. PMID- 2586547 TI - Sister-chromatid exchanges in 52 Korean women living in the vicinity of an industrial complex. AB - Sister-chromatid exchanges (SCE) were examined in the peripheral lymphocytes of 52 Korean women living in the vicinity of an industrial complex. They were generally non-smokers ranging from 22 to 56 years of age. The mean SCE score of the volunteers was 6.01 +/- 0.15 (SE). Only coffee intake produced a significant increase of SCE by comparison with the mean SCE for those that did not take coffee. Other parameters, including alcohol intake, working in industry and the presence of hepatitis B surface antigen (HBsAg), did not produce an increase in SCE. There was no effect on SCE due to age. PMID- 2586548 TI - A time-course study on effects of aluminium on mitotic cell division in Allium sativum. AB - Cytotoxic effects of aluminium sulphate on root-tip cells of Allium sativum during a time-course study and during recovery were observed. The endpoints considered were mitotic index and frequencies of aberrant cells and micronuclei induced. Chronic exposure induced mitotic depression and abnormal cells to a degree directly proportional to the concentration used and the period of treatment up to 24 h. A reduction of the early higher level of toxicity was noticed following 48 h of treatment and subsequent recovery in aluminium-free nutrient media in experiments carried out with lower concentrations. PMID- 2586549 TI - Chromosome aberration test and sister-chromatid exchange assay in murine bone marrow cells after in vivo exposure to D-penicillamine alone or combined with cyclophosphamide. PMID- 2586551 TI - Role of the viral and cellular encoded thymidine kinase in the repair of UV irradiated herpes simplex virus. AB - A strain of herpes simplex type 1 (HSV-1:KOS) encoding a functional thymidine kinase (tk+) gene and a thymidine kinase deficient (tk-) mutant strain (HSV 1:PTK3B) were used as probes to examine the repair of UV-damaged viral DNA in one tk- (143) and two tk+ (R970-5 and AC4) human cell lines. UV survival for each HSV 1 strain was similar for infection of both tk- and tk+ cells suggesting that the repair of viral DNA was not dependent on the expression of a functional cellular tk gene. In contrast, UV survival of HSV-1:PTK3B was substantially reduced compared to HSV-1:KOS when infecting all 3 human cell lines, as well as Vero monkey kidney cells and LPM1A mouse cells. These results suggest that the repair of UV-irradiated HSV-1 in lytically infected mammalian cells depends, in part at least, on the expression of the viral encoded tk. PMID- 2586550 TI - Inhibition of the adaptive response of human lymphocytes to very low doses of ionizing radiation by the protein synthesis inhibitor cycloheximide. AB - When human lymphocytes are preirradiated with 1 cGy of X-rays, the cells become less sensitive to subsequent exposures to high doses of about 150 cGy in that approximately one-half as many chromatid aberrations are induced as expected. This adaptation has been attributed to the induction of repair enzymes (proteins) some 4-6 h after the initial low-dose exposure. Experiments have now been carried out showing that application of the protein synthesis inhibitor cycloheximide at this time, but not earlier, prevents the adaptive response. PMID- 2586552 TI - New method for quantitating yeasts in clinical specimens. AB - Existing methods for quantitating yeasts in clinical specimens usually rely on plate counts of sediments. A new method has been developed which uses filtration to concentrate a sample and fluorescence microscopy to facilitate counting. This method is fast and easy to perform and can be used for a wide variety of specimens including urine, mouthwash water, and vaginal fluid. PMID- 2586554 TI - Intentional injuries among children and adolescents in Massachusetts. AB - We estimated age-specific and sex-specific incidence rates of intentional injuries (assaults or suicide attempts) occurring between 1979 and 1982 in a population of 87,022 Massachusetts children and adolescents under 20 years of age in 14 communities with populations of 100,000 or less. The average annual incidence of intentional injuries treated at a hospital was estimated to be 76.2 per 10,000 person-years. Overall, 1 in 130 children was treated each year for an intentional injury. More than 85 percent of the injuries resulted from assaults, such as fights, rape, and child battering; 11.4 percent were self-inflicted. Intentional injuries were most common among adolescents. Each year, 1 in 42 teenage boys was treated for an assault-related injury, and 1 in 303 teenage girls was seen for a suicide attempt. Repeated episodes of intentional injury were identified in 4.3 percent of the children. In this population, intentional injuries accounted for 3.4 percent of all injuries but 9.8 percent of hospital admissions and 15.7 percent of deaths from injury. The rate of intentional injury was directly correlated with both the degree of urbanization and the poverty level of the community of residence. We conclude that intentional injuries are relatively common in this population and that attempts to prevent them must be directed to the children who are at greatest risk. PMID- 2586553 TI - Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons. AB - We estimated the prevalences of Helicobacter pylori (formerly called Campylobacter pylori) infection and histologic gastritis in 113 asymptomatic persons, using endoscopic biopsy of the gastric antrum and corpus. Unsuspected lesions, mainly mucosal erosions, were revealed at endoscopy in 16 subjects (14 percent). Gastritis was found in 42 subjects (37 percent), of whom 36 (32 percent of the total) were found to be infected with H. pylori on the basis of hematoxylin-eosin staining. H. pylori was not found in any of the 71 subjects with normal histologic features. Gastritis and H. pylori were noted in both the antrum and corpus in 75 percent of those infected (n = 27). The prevalence of H. pylori infection increased from 10 percent (2 of 20 subjects) in those between the ages of 18 and 29, to 47 percent (7 of 15) in those between the ages of 60 and 69, but the effect of age did not reach statistical significance. The prevalence of gastritis increased significantly with advancing age. Stepwise logistic regression analysis revealed that the relative risk for H. pylori infection associated with recent (within six months) antibiotic use was 5.8 (95 percent confidence interval, 1.5 to 22.1), whereas the relative risk was 6.5 (95 percent confidence interval, 1.4 to 29.2) for those who had never used bismuth compounds. We conclude that histologic gastritis and H. pylori infection commonly occur in the stomach of apparently normal persons and increase in prevalence with advancing age. All the subjects with H. pylori infection had gastritis, suggesting a possible etiologic role for the bacterium in the histologic lesion. PMID- 2586555 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 49-1989. A 71-year-old man with thrombocytopenia and hypotension after resection of a colonic carcinoma. PMID- 2586556 TI - Cocaine and vasospasm. PMID- 2586557 TI - Neuronal proteins and paraneoplastic syndromes. PMID- 2586558 TI - Antihypertensive effects of fish oil. PMID- 2586559 TI - Acid-base status in circulatory failure. PMID- 2586560 TI - An unusual abdominal mass in an elderly woman. PMID- 2586561 TI - Prevention of falls in the elderly. PMID- 2586562 TI - Pressure necrosis from intermittent-pneumatic-compression stockings. PMID- 2586563 TI - How house officers spend their nights. PMID- 2586564 TI - Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. AB - We used end-point-dilution cultures to measure the level of infectious human immunodeficiency virus type 1 (HIV-1) in peripheral-blood mononuclear cells (PBMC) and plasma of 54 infected patients who were not receiving antiviral chemotherapy. HIV-1 was recovered from the plasma and PBMC of every seropositive patient, but from none of 22 seronegative control subjects. The mean titers in plasma were 30, 3500, and 3200 tissue-culture-infective doses (TCID) per milliliter for patients with asymptomatic infection, the acquired immunodeficiency syndrome (AIDS), and the AIDS-related complex, respectively. In PBMC, the mean titers were significantly higher for symptomatic patients (AIDS, 2200, and AIDS-related complex, 2700 TCID per 10(6) PBMC) than asymptomatic patients (20 TCID per 10(6) PBMC). The values for the symptomatic patients were considered to indicate that at least 1 in 400 circulating mononuclear cells harbored HIV-1. The HIV-1 titers of seven patients with AIDS or AIDS-related complex treated with zidovudine for four weeks decreased significantly in plasma but not in PBMC. In addition, the mean titer in the plasma of 20 patients receiving long-term zidovudine treatment (130 TCID per milliliter) was 25-fold lower than the mean for comparable untreated patients with AIDS or AIDS-related complex. We conclude that the levels of HIV-1 in plasma and PBMC are much higher than previous estimates. This high degree of HIV-1 viremia raises the possibility that the direct cytopathic effect of this retrovirus alone may be sufficient to explain much of the pathogenesis of AIDS. PMID- 2586565 TI - Peritoneovenous shunting as compared with medical treatment in patients with alcoholic cirrhosis and massive ascites. Veterans Administration Cooperative Study on Treatment of Alcoholic Cirrhosis with Ascites. AB - The optimal management of severe ascites in patients with alcoholic cirrhosis has not been defined. in a 5 1/2-year study, we randomly assigned 299 men with alcoholic cirrhosis, who had persistent or recurrent severe ascites despite a standard medical regimen, to receive either intensive medical treatment or peritoneovenous (LeVeen) shunting. We identified three risk groups: Group 1 had normal or mildly abnormal results on liver-function tests, Group 2 had more severe liver dysfunction or previous complications, and Group 3 had severe prerenal azotemia without kidney disease. For the patients who received the medical treatment and those who received the surgical treatment combined, the median survival times were 1093 days in Group 1, 222 days in Group 2, and 37 days in Group 3 (P less than or equal to 0.01) for all comparisons). For all the groups combined, the median time to the resolution of ascites was 5.4 weeks for medical patients and 3.0 weeks for surgical patients (P less than 0.01). Within each risk group, mortality during the initial hospitalization and median long term survival were similar among patients receiving either treatment. However, the median time to the recurrence of ascites in Group 1 was 4 months in medical patients, as compared with 18 months in surgical patients (P = 0.01); in Group 2 it was 3 months in medical patients as compared with 12 months in surgical patients (P = 0.04). The median duration of hospitalization was longer in medical patients than in surgical patients (6.1 vs. 2.4 weeks in Group 1 [P less than 0.001] and 5.0 vs. 3.1 weeks in Group 2 [P less than 0.01]). Group 3 was too small to permit a meaningful comparison. During the initial hospitalization, the incidence of infections, gastrointestinal bleeding, and encephalopathy was similar among the medical and surgical patients. We conclude that peritoneovenous shunting alleviated disabling ascites more rapidly than medical management. However, survival was closely related to the severity of the illness at the time of randomization and was not altered by shunting. PMID- 2586566 TI - The relation of aspirin use during the first trimester of pregnancy to congenital cardiac defects. AB - It has been hypothesized that the ingestion of aspirin by women during pregnancy increases their infants' risk of certain congenital heart defects. Using data from a large program of case-control surveillance of congenital malformations, we evaluated this hypothesis. The case groups were made up of infants with any structural cardiac defect (n = 1381) and five selected cardiac defects (the subgroups were not mutually exclusive): aortic stenosis (n = 43), coarctation of the aorta (n = 123), hypoplastic left ventricle (n = 98), transposition of the great arteries (n = 210), and conotruncal defects (n = 791). First-trimester aspirin use among the mothers of these infants was compared with that among the mothers of a control group of infants with other malformations (n = 6966). The prevalence of any maternal aspirin use was similar for cases (25 to 33 percent) and controls (27 percent). The relative risks (and 95 percent confidence interval) among infants whose mothers were aspirin users as compared with those whose mothers did not use aspirin, adjusted for potential confounding factors, were 0.9 (0.8 to 1.1) for any cardiac defect, 1.2 (0.6 to 2.3) for aortic stenosis, 1.0 (0.6 to 1.4) for coarctation, 0.9 (0.6 to 1.4) for hypoplastic left ventricle, 0.9 (0.6 to 1.2) for transposition of the great arteries, and 1.0 (0.8 to 1.2) for conotruncal defects. Furthermore, no dose-effect pattern was identified. The findings of this study indicate that aspirin use during the first trimester of pregnancy does not increase the risk of congenital heart defects in relation to that of other structural malformations. PMID- 2586567 TI - Familial Cushing's syndrome due to primary pigmented nodular adrenocortical disease. Reinvestigation 50 years later. PMID- 2586568 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 50-1989. A 17-year-old boy with right-lower-lobe pneumonitis and asthma. PMID- 2586569 TI - HIV revealed: toward a natural history of the infection. PMID- 2586570 TI - Treatment of refractory ascites. PMID- 2586571 TI - Human immunodeficiency virus type 1 infection in homosexual men who remain seronegative for prolonged periods. PMID- 2586572 TI - Polymerase chain reaction for seronegative health care workers with parenteral exposure to HIV-infected patients. PMID- 2586573 TI - Frequent isolation of HIV-1 from the blood of patients receiving zidovudine (AZT) therapy. PMID- 2586574 TI - Controversies in the management of bleeding esophageal varices. PMID- 2586575 TI - More on oral iron and the Hemoccult test. PMID- 2586576 TI - Life-threatening reactions to intravenous protamine. PMID- 2586577 TI - Resolution of high-output cardiac failure following treatment of multiple myeloma. PMID- 2586578 TI - The day the Nyanga came to call. PMID- 2586579 TI - Psychiatric care in the South African context. PMID- 2586581 TI - Tegaderm-wound management. PMID- 2586580 TI - Getting black psychiatric patients to comply with treatment. PMID- 2586582 TI - Updating the management of the burned child. PMID- 2586583 TI - Occupational health in commerce. Quo vadis? PMID- 2586584 TI - Cancer care and resource centre. PMID- 2586585 TI - Occupational stress and the oncology nurse. PMID- 2586586 TI - The role of the clinical nurse specialist at Groote Schuur. PMID- 2586587 TI - Cardio-pulmonary by-pass in children. PMID- 2586588 TI - Nursing care 2. PMID- 2586590 TI - Conduct unbecoming. PMID- 2586589 TI - Moderation of abortion debate. PMID- 2586592 TI - Databases: Johns Hopkins as international host. PMID- 2586591 TI - Nobel dispute continues. PMID- 2586593 TI - Max-Planck Society: Zacher is new president. PMID- 2586594 TI - Fraud in science: Indian zoologist suspected. PMID- 2586595 TI - Japan: huge profit from drugs. PMID- 2586596 TI - Biotechnology: Celltech to change hands? PMID- 2586597 TI - Food irradiation: limited use approved in India. PMID- 2586598 TI - Genetic testing: CF screening premature? PMID- 2586599 TI - Human frontier program: Strasbourg office opens. PMID- 2586600 TI - No paying twice. PMID- 2586601 TI - Nobel infallibility. PMID- 2586602 TI - Reasonable doubt? PMID- 2586603 TI - The nature of science. PMID- 2586604 TI - Immunology. Tolerance: a second mechanism. PMID- 2586605 TI - Palaeontology: ears and vertebrate evolution. PMID- 2586606 TI - Archaeology: age and the female form. PMID- 2586607 TI - DNA fingerprints: Victims or perpetrators of DNA turnover? PMID- 2586608 TI - Homoeopathic test. PMID- 2586609 TI - Induction of self-tolerance in mature peripheral B lymphocytes. AB - In transgenic mice, mature peripheral B lymphocytes in lymphoid follicles, like immature B cells, are rendered tolerant by encounter with self-antigen, provided receptor occupancy by self-antigen exceeds a critical threshold. The tolerant state of the B cell is closely correlated with down-regulation of membrane IgM but not IgD antigen-receptors. Identical changes in antigen-receptor expression occur in a subset of follicular B cells in nontransgenic mice, suggesting that clonally silenced self-reactive cells are common in the peripheral B-cell repertoire. PMID- 2586610 TI - Discovery of the earliest-known tetrapod stapes. AB - The evolution of the middle ear is central to the discussion of how the first tetrapods adapted to life on land as well as their phylogeny. Here I report the discovery of the stapes of Acanthostega gunnari, from the Upper Devonian of east Greenland. This is the earliest tetrapod stapes so far described, and it throws new light on both these aspects of early tetrapod biology. It has been assumed that the common inheritance of all early tetrapods was a light, rod-like stapes associated with a temporal notch in the otic region that was thought to have supported a tympanum, or eardrum. The stapes would have conducted vibrations from the tympanum to the otic capsule. By contrast, the stapes of Acanthostega was stout with a broad distal ramus associated with the temporal notch. I suggest that the temporal notch of Acanthostega and other early tetrapods supported a spiracular opening rather than a tympanum, and that the stapes controlled palatal and spiracular movements in ventilation. PMID- 2586611 TI - Ocular dominance plasticity in adult cat visual cortex after transplantation of cultured astrocytes. AB - During a critical restricted period of postnatal development, the visual cortical circuitry is susceptible to modifications that are dependent on experience. If vision is restricted to only one eye during this period, the territories innervated by the deprived eye shrink considerably, whereas those innervated by the non-deprived eye expand, and the deprived eye loses the ability to influence almost all of the cells in the cortex. Thus, changes in ocular dominance are paralleled and possibly mediated by synapse elimination and axonal sprouting. Hypotheses about the mechanisms underlying ocular-dominance plasticity assume the activation of NMDA (N-methyl-D-aspartate) receptors and subsequent calcium influx as a trigger of synaptic modifications. In addition, plasticity relies on functional neuromodulatory afferents. On the basis of immunocytochemical studies, it was recently proposed that the presence of immature astrocytes is a prerequisite for visual cortical plasticity, and that the end of the critical period is causally linked to the maturation of astrocytes. Here we report, in support of this hypothesis, that resupplementation of the visual cortex of adult cats with astrocytes cultured from the visual cortex of newborn kittens reinduces ocular-dominance plasticity in adult animals. PMID- 2586612 TI - Target size regulates calibre and myelination of sympathetic axons. AB - Axons in vertebrate peripheral nerves are ensheathed by Schwann cells. For some axons, this sheath consists of a single layer of glial cell cytoplasm and plasma membranes; for other axons, Schwann cells form multilayered myelin. Whether or not a Schwann cell makes myelin is determined by a signal from the axon, but the nature of this signal is not known. Here I show that sympathetic postganglionic axons, which are normally not myelinated, become myelinated when their calibre is increased as a result of increasing the size of the peripheral target they innervate. This result implies that axon calibre, which is known to be correlated with myelination, is in fact the crucial determinant of whether an axon becomes myelinated. Furthermore, the finding that increasing or decreasing target size causes corresponding increases or decreases in axon size indicates that axon calibre is itself regulated by retrograde signals from peripheral target tissues. PMID- 2586613 TI - Developmental regulation of stage-specific ribosome populations in Plasmodium. AB - The Plasmodium parasites are so far unique in biology in possessing developmentally regulated ribosomal RNA gene units. Two different genes encode their small subunit rRNAs: one gene (A) yields transcripts predominant in the asexual blood-stage parasites, and the other (C) is mainly transcribed in the sporozoite forms that develop in the mosquito. Developmental control of events allowing a switch in the complement of ribosomes must coordinate the production of the new class with selective inactivation and removal of the old. We show here that in P. falciparum the switch, from A to C gene expression involves the control of rRNA processing, allowing accumulation of precursor C-gene transcripts in gametocytes. These precursor molecules are processed to mature size in the zygote and the early ookinete, where both transcription and processing of the C gene rRNA seem to be accelerated. As the C-gene precursor rRNA appears, a defined and limited pattern of breakdown of the dominant A-gene rRNA occurs, in which conserved, functionally active sequences involved in the termination of translation and elongation are targeted. By the late oocyst stage, the A-gene transcripts are virtually replaced by mature C-gene transcripts. PMID- 2586615 TI - The conformation of the DNA double helix in the crystal is dependent on its environment. AB - Studies of the crystal structures of more than 30 synthetic DNA fragments have provided structural information about three basic forms of the double helix: A-, B- and Z-form DNA. These studies have demonstrated that the DNA double helix adopts a highly variable structure which is related to its base sequence. The extent to which such observed structures are influenced by the crystalline environment can be found by studying the same molecule in different crystalline forms. We have recently crystallized one particular oligomer in various crystal forms. Here we report the results of structural analyses of the different crystal structures and demonstrate that the DNA double helix can adopt a range of conformations in the crystalline state depending on hydration, molecular packing and temperature. These results have implications on our understanding of the influence of the environment on DNA structure, and on the modes of DNA recognition by proteins. PMID- 2586614 TI - Molecular basis of lipid transfer protein deficiency in a family with increased high-density lipoproteins. AB - Plasma high density lipoproteins (HDL) are a negative risk factor for atherosclerosis. Increased HDL is sometimes clustered in families, but a genetic basis has never been clearly documented. The plasma cholesteryl ester transfer protein (CETP) catalyses the transfer of cholesteryl ester from HDL to other lipoproteins and therefore might influence HDL levels. Using monoclonal antibodies, we show that CETP is absent in two Japanese siblings who have markedly increased and enlarged HDL. Furthermore, they are homozygous for a point mutation in the 5'-splice donor site of intron 14 of the gene for CETP, a change that is incompatible with normal splicing of pre-messenger RNA. The results indicate that the family has an inherited deficiency of CETP due to a gene splicing defect, and illustrate the key role that CETP has in human HDL metabolism. PMID- 2586616 TI - Deciding about embryo research. PMID- 2586617 TI - Human genome project a cause of friction. PMID- 2586618 TI - HIV testing. UK blood screening begins. PMID- 2586619 TI - IVF: regulation or prohibition? PMID- 2586620 TI - Missed opportunity in biology. PMID- 2586621 TI - Immunology. Stimulating killer cells. PMID- 2586622 TI - Neuroethology. Deceptively simple behaviour. PMID- 2586623 TI - Ancient bone DNA amplified. PMID- 2586624 TI - Genetic correlations between morphology and antipredator behaviour in natural populations of the garter snake Thamnophis ordinoides. AB - The genetic coupling of morphology and behaviour means that the evolution of the two types of traits will not be independent: changes in behaviour will result in changes in morphology and vice versa. This might explain nonadaptive differences in morphology through indirect selection on correlated characters of other categories. Genetic correlations between morphology and behaviour are also the basis for some models of sympatric speciation and of the stability of polymorphisms. Morphology and behaviour are often correlated in nature and a genetic basis for such couplings has been demonstrated. I present here evidence that colour pattern and antipredator behaviour are genetically coupled in natural populations of the garter snake Thamnophis ordinoides. Similar phenotypic correlations between pattern and behaviour exist among species of North American snakes, indicating that selection for particular combinations of traits may help to maintain genetic covariances and colour polymorphism in Thamnophis ordinoides. PMID- 2586625 TI - Independent hemispheric attentional systems mediate visual search in split-brain patients. AB - The primate visual system is adept at identifying objects embedded within complex displays that contain a variety of potentially distracting elements. Theories of visual perception postulate that this ability depends on spatial selective attention, a mechanism analogous to a spotlight or zoom lens, which concentrates high-level processing resources on restricted portions of the visual field. Previous studies in which attention was pre-cued to specific locations in the visual field have shown that the spotlight has a single, unified focus, even in the disconnected hemispheres of patients who have undergone surgical transection of the corpus callosum. Here we demonstrate that an independent focus of attention is deployed by each of the surgically separated hemispheres in a visual search task, such that bilateral stimulus arrays can be scanned at a faster rate by 'split-brain' subjects than by normal control subjects. The attentional system used for visual search therefore seems to be functionally and anatomically distinct from the system that mediates voluntary orienting of attention. PMID- 2586626 TI - Recovery of spatial learning deficits after decay of electrically induced synaptic enhancement in the hippocampus. AB - A widespread interest in a long-lasting form of synaptic enhancement in hippocampal circuits has arisen largely because it might reflect the activation of physiological mechanisms that underlie rapid associative learning. As its induction normally requires the 'Hebbian' association of activity on a number of input fibres, we refer to the process as long-term enhancement (LTE) rather than long-term potentiation (LTP), to emphasize its distinction from the ubiquitous, non-associative 'potentiation' phenomena that occur at most synapses, including those exhibiting LTE. Among other evidence that LTE might actually have a role in associative memory is the demonstration that repeated high-frequency stimulation, which saturated the inducible LTE, caused a severe deficit in spatial learning, although it had no effect on well established spatial memory. These results were consistent with a widespread view that information need only temporarily be stored in the hippocampal formation in order for long-term memories to be established in neocortical circuits. In this context, it is important to understand whether the possible underlying synaptic changes are of a permanent character, or are relatively transient. A second question is whether the actual cause of the observed learning deficit is the distruption of the synaptic weight distribution, and/or the limitation of further synaptic change, which presumably results from experimental saturation of the LTE mechanism. Alternatively, the deficit could be a consequence of some unobserved secondary effect of the high frequency electrical stimulation. Here we demonstrate that learning capacity recovers in about the same time that it takes LTE to decay, which strongly favours the first possibility and supports the idea that LTE-like processes actually underlie associative memory. PMID- 2586627 TI - Patch clamp studies of single cell-fusion events mediated by a viral fusion protein. AB - To enter cells, viruses must fuse their envelope with a host cell membrane. Fusion is mediated by specific, membrane-spanning fusion proteins, of which the influenza virus haemagglutinins (HA) are the best characterized. Several HAs have been sequenced, and the crystal structure of the major part of one HA is known. The conditions for fusion and some of the rearrangements in the HA that accompany fusion are well understood, but it remains unclear how HA causes bilayers to fuse. We have observed, in real time, unitary cell-fusion events caused by HA. Fibroblasts expressing HA were induced to fuse with red blood cells by a rapid drop in pH. Fusion was monitored by fluorescence microscopy, and by measuring the membrane conductance and capacitance of the fibroblast. The earliest event observed was the sudden opening of an aqueous pore connecting the cytoplasms of the fusing cells. Initially, the pore conductance often fluctuated between zero and approximately 600 pS, as if the pore were opening and closing repeatedly. Later, it increased over tens of seconds, as if the pore dilated. We suggest that, as in exocytosis, HA-mediated membrane fusion begins with the formation of a narrow pore. Based on the conductance, we estimate the initial diameter of the pore to be no more than twice that of a gap junction channel. PMID- 2586629 TI - [Peripheral vision--function and significance]. AB - The human retina may be divided into two parts, representing different functional capabilities: the center, i.e., the fovea, and the much greater periphery. Under photopic conditions the fovea has a very high spatial resolution, a high light difference sensitivity, and a good perception of slow movements. Opposed to this the periphery shows an especially high temporal resolution and a good perception of fast movements. This enables the visual system to detect dangerous objects appearing in the periphery as soon as possible and to induce a detailed analysis in the fovea after triggering a fixational movement. PMID- 2586628 TI - In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine. AB - Cytotoxic T lymphocytes (CTL) constitute an essential part of the immune response against viral infections. Such CTL recognize peptides derived from viral proteins together with major histocompatibility complex (MHC) class I molecules on the surface of infected cells, and usually require in vivo priming with infectious virus. Here we report that synthetic viral peptides covalently linked to tripalmitoyl-S-glycerylcysteinyl-seryl-serine (P3CSS) can efficiently prime influenza-virus-specific CTL in vivo. These lipopeptides are able to induce the same high-affinity CTL as does the infectious virus. Our data are not only relevant to vaccine development, but also have a bearing on basic immune processes leading to the transition of virgin T cells to activated effector cells in vivo, and to antigen presentation by MHC class I molecules. PMID- 2586630 TI - Segregation of color and form. Intact spatial wavelength discrimination in strabismic amblyopia. PMID- 2586631 TI - Phylogenetic relationships of three Indian murine rats deduced from mitochondrial DNA restriction fragment analysis. PMID- 2586633 TI - [3H]ICS 205-930 labels 5-HT3 recognition sites in membranes of cat and rabbit vagus nerve and superior cervical ganglion. AB - The binding characteristics of [3H]ICS 205-930, a 5-hydroxytryptamine 5-HT3 receptor antagonist, were investigated in membranes prepared from cat and rabbit vagus nerve (VN) and superior cervical ganglion (SCG). The autoradiographic localisation of 5-HT3 recognition sites was also assessed using [3H]ICS 205-930 in slices from cat medulla oblongata, nodose ganglion and vagus nerve. [3H]ICS 205-930 bound to a homogeneous population of high affinity recognition sites in cat VN: Bmax = 201 +/- 43 fmol/mg protein, pKD = 9.26 +/- 0.17 and SCG: Bmax = 291 +/- 40 fmol/mg, pKD = 9.35 +/- 0.80 (n = 3). Competition experiments performed in membranes from cat VN and SCG with agonists and antagonists suggested the presence of a homogeneous population of [3H]ICS 205-930 recognition sites. Competition curves were steep and monophasic and were best fitted by a 1 receptor site model. The following rank order of affinity for [3H]ICS 205-930 binding sites was observed with antagonists: SDZ 206-830 = ICS 205-930 greater than BRL 43694 greater than SDZ 206-792 greater than quipazine greater than MDL 72222 greater than metoclopramide greater than mCPP and agonists: 2-methyl-5-HT = 5-HT greater than phenylbiguanide. A similar profile was observed for a limited series of compounds in rabbit membranes. Drugs acting at 5-HT1, 5-HT2 and dopamine receptors (domperidone, spiperone and metergoline) showed very low affinities for [3H]ICS 205-930 recognition sites. The sites labelled with [3H]ICS 205-930 in vagus nerve and superior cervical ganglion of both species displayed the pharmacological profile of a 5-HT3 receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2586632 TI - Down-regulation of tryptamine binding sites following chronic molindone administration. A comparison with responses of dopamine and 5-hydroxytryptamine receptors. AB - The present study assessed changes of tryptamine, dopamine D2, 5-HT1 and 5-HT2 binding sites in rat brain following chronic treatment with low (5 mg/kg/day) and high (40 mg/kg/day) doses of molindone, a clinically effective psychotropic drug. The high-dose molindone treatment produced a decrease in the number of tryptamine binding sites while both high and low doses caused an increase in the number of dopamine D2 binding sites in the striatum. No significant changes were observed in either 5-HT1 or 5-HT2 binding sites in the cerebral cortex. Competition binding experiments showed that molindone was a potent inhibitor at dopamine D2 but less effective at tryptamine, 5-HT1 and 5-HT2 binding sites. The inhibition activity of molindone towards type A monoamine oxidase produced a significant increase in endogenous tryptamine accumulation rate which was much higher than that of dopamine and 5-HT. These findings suggest that the reduction in the number of tryptamine binding sites produced by chronic molindone administration is related to monoamine oxidase inhibition and that the increase in the number of dopamine D2 binding sites is correlated to receptor blocking activity of the drug. PMID- 2586634 TI - Cholinomimetic activities of minaprine. AB - The cholinomimetic activities of the antidepressant drug minaprine have been investigated, in vitro and in vivo, in rodents. Minaprine, and its metabolite SR 95070B [3-(2-morpholinoethylamino)-4-methyl-6-(2-hydroxyphenyl) pyridazine hydrochloride] selectively displaced [3H]-pirenzepine from its cortical and hippocampal binding sites, and only weakly inhibited the binding of [3H]-N methylscopolamine in either the rat cerebellum, heart and salivary glands, or the guinea-pig ileum. In mice, none of these drugs induced the typical cholinergic side-effects up to lethal doses. Minaprine and SR 95070B antagonized rotations induced by an intrastriatal injection of pirenzepine in mice, after intraperitoneal and/or oral administration. Minaprine also antagonized atropine induced mydriasis in mice. Both minaprine and SR 95070B potentiated the tremorigenic effect of oxotremorine without inducing tremor when injected alone. Finally, minaprine and SR 95070B, after parenteral and/or oral injection, antagonized the scopolamine-induced deficit in passive avoidance learning, and enhanced short-term retention in the social memory test, in rats. The muscarinic agonists arecoline, oxotremorine and RS 86 [2-ethyl-8-methyl-2,8 diazaspiro-4,5 decan-1,3 dion hydrobromide], as well as the acetylcholine esterase inhibitors physostigmine and tacrine were active in most of these models. These results indicate that minaprine, and its metabolite SR 95070B, have cholinomimetic activities which could be, at least in part, mediated by their selective affinity for M1 muscarinic receptors. Thus minaprine could represent a potential useful drug for the treatment of senile dementias and cognitive impairments occurring in elderly people. PMID- 2586635 TI - Modelling frequency- and voltage-dependent effects of a class I antiarrhythmic drug (nicainoprol) on Vmax of the cardiac action potential from guinea-pig papillary muscle. AB - Frequency- and voltage-dependent effects of a class I antiarrhythmic agent (nicainoprol) on the maximal upstroke velocity (Vmax) of the action potential of guinea-pig papillary muscle are compared with the effects predicted by a kinetic model of frequency- and voltage-dependent block of fast sodium channels. The model is based on the guarded-receptor hypothesis, which assumes a constant affinity binding site with the drug access to and egress from the binding site being controlled by the channel conformational state. At normal resting membrane potential (RMP approximately -86 mV) nicainoprol (3.3 x 10(-6) mol/l and 10(-5) mol/l) causes no Vmax-reduction after a resting period (i.e. no resting block) but a frequency-dependent decrease of Vmax (frequency-dependent block), which saturates at above 2.0 Hz. Both, resting and frequency-dependent block strongly depend on the RMP in a way that the frequency-dependent block decreases with depolarizing RMP while the resting block increases. Development of and recovery from frequency-dependent block is faster at depolarized RMP. These results can be interpreted in terms of the guarded-receptor hypothesis with nicainoprol preferentially binding to inactivated sodium channels. All its effects on Vmax can be fully described by only three model parameters: a binding rate coefficient (kB = 8.49 x 10(3) mol-1.1.s-1), an unbinding rate coefficient (k-B = 6.24 x 10( 2).S-1), and a parameter with the meaning of an electrical location of the binding site (about 35% on the way through the membrane field from the extracellular surface). PMID- 2586637 TI - Endogenous noradrenaline impairs the prostaglandin-induced inhibition of noradrenaline release. AB - The effects of prostaglandin E2 (PGE2) on electrically evoked noradrenaline release in rat brain cortex were studied under conditions under which autoinhibition of release was avoided. When stimulation was carried out with 36 pulses at 3 Hz, 1 mumol/l PGE2, produced about 50% inhibition of release. In the presence of the alpha 2-adrenoceptor antagonist yohimbine (1 mumol/l) the effect of PGE2 was markedly increased. When release was elicited by 3 pulses/100 Hz the period of stimulation was too short to permit development of autoinhibition by released noradrenaline. Then the concentration-response-curve for PGE2 was very similar to that obtained under the above conditions (36 pulses/3 Hz, in the presence of yohimbine). These data suggest that both the alpha 2-adrenoceptor and the PGE2-receptor are linked to a common pathway. Since indometacin (10 mumol/l) did not enhance evoked transmitter release, an influence of endogenous PG's on in vitro release of noradrenaline from rat brain cortex slices can be excluded. PMID- 2586636 TI - Effects of cromakalim (BRL 34915) on potassium conductances in CA3 neurons of the guinea-pig hippocampus in vitro. AB - The action of the potassium channel activator, cromakalim (BRL 34915), on membrane potential, input resistance and current-voltage-relationship of CA3 neurons in a slice preparation of the guinea-pig hippocampus was investigated by means of intracellular recordings. In the presence of tetrodotoxin, cromakalim (30-100 mumol/l) produced a hyperpolarization up to 4 mV associated with a decrease in input resistance up to 10 MOhms. Determination of the equilibrium potential of the cromakalim action revealed that the hyperpolarization is due to the activation of a potassium conductance. This cromakalim-activated potassium conductance was voltage-dependent, i.e. it increased with hyperpolarization. Among a number of potassium channel blockers tested, only Cs+ (2 mmol/l) and Ba2+ (0.5 mmol/l) were able to inhibit the cromakalim-induced effects. Simultaneously, both cations suppressed the hyperpolarizing inward rectification (anomalous rectification) in these neurons, indicating that cromakalim activated or potentiated an inwardly rectifying potassium conductance. In addition, cromakalim slightly enhanced both amplitude and duration of afterhyperpolarizations following single calcium-dependent action potentials, suggesting that cromakalim might have a weak facilitatory effect on calcium-dependent potassium conductances. PMID- 2586638 TI - Rationally rationing health care: effectiveness research by another name? PMID- 2586642 TI - Criticism on "Physician as a customer" article. PMID- 2586641 TI - The time is rich with opportunity. PMID- 2586640 TI - Developing an incentive program for home health nurses. AB - After revamping agency operations, this agency was able to devise a voluntary incentive bonus program to address recruitment, retention, and quality concerns while controlling costs. PMID- 2586639 TI - Lessons from the Canadian health care system. AB - In a recent poll, 89% of Americans stated that the U.S. health care system needs fundamental changes; 61% said they would prefer a system like Canada's to the system currently in place. How does the Canadian system work? How well has it served Canadian's health needs? PMID- 2586643 TI - Managing temporary staffing services: selecting the right agency. AB - Hospitals frequently must resort to using temporary staffing agencies. As an informed client and skilled negotiator, the nurse executive can obtain the highest quality and best price possible. PMID- 2586644 TI - The hospital based staffing agency. AB - Before a hospital considers creating an internal staffing agency, a detailed business plan must be developed. By addressing marketing and operational issues in advance, nurse executives can avoid unnecessary business problems. PMID- 2586645 TI - A model for hospital nurse retention: new findings. AB - This study of hospital nurse retention culminated in identifying three principles for incorporation into nurse retention models and a comprehensive model for nurse retention program development. PMID- 2586646 TI - Moving your nursing department forward: winning strategies for nurse executives. PMID- 2586647 TI - Nurse/physician collaboration: a cost/quality issue for the nurse manager. AB - Excellence in nurse-physician relationships is possible and feasible, beginning and ending with the nurse manager setting the climate and culture that fosters mutual respect. As Leah Curtin (1982, p. 8) states, "We may be irritants, but we are not adversaries: Physicians know that patients need good nursing care and nurses know that patients need good medical care. Generally speaking, neither is possible in the absence of the other." PMID- 2586648 TI - [Parathyroid gland carcinoma or the importance of the 'small print']. PMID- 2586649 TI - [Surgery in children. The need to focus; an advisory by the Health Council]. PMID- 2586650 TI - [Value of the preoperative examination]. PMID- 2586651 TI - [Medicine and language; side effect or meaning?]. PMID- 2586652 TI - [Evaluation consensus melanoma of the skin based on pathologic-anatomic reports]. AB - On September 15, 1984 a consensus development conference on cutaneous melanoma was held. The consensus statement included explicit guidelines on the management of patients with primary and metastatic melanoma. For evaluation of the post conference compliance among clinicians, 383 histopathological reports prepared by 19 pathology laboratories in 1986 and 384 reports dating from 1988 were analysed and the data compared with those in 324 reports dating from 1983, one year before the consensus conference. The present study is confined to the details of the histopathological description and the type of diagnostic procedure conducted by the physician. There was a substantial increase in the percentages of cases in which Breslow thickness was reported (1983: 83%, 1986: 91%, 1988: 97%). Also, other microscopical parameters were more detailed after the consensus conference. PMID- 2586653 TI - [Once again, the routine preoperative thorax photo]. AB - A prospective study of the influence of radiological findings upon operation policy was carried out in 810 patients over 40 years of age who underwent elective non cardiopulmonary surgery. Only in 5 patients did it appear that a preoperative X-ray yielded any relevant extra information, and only in 3 cases was the operation planning influenced. If no preoperative chest X-rays has been taken, all except one of the significant abnormalities would have been discovered anyway. By differentiating between patients graded ASA 1 and those classed ASA 2 or higher, it would be possible to reduce the number of preoperative chest X-rays by 41% without any loss of precision. Preoperative chest X-rays in patients over 40 years of age scheduled for non-cardiopulmonary surgery can be restricted to those whose history requires further radiological analysis. PMID- 2586654 TI - [Laboratory findings for the preoperative evaluation of patients with otherwise no organic disorders]. AB - The efficiency of preoperative laboratory screening of normal, healthy patients was investigated. Preoperative test results of 1311 consecutive patients were collected. Data on haemoglobin, serum potassium, serum creatinine and serum ALAT were routinely obtained. 736 patients were classified by history and physical examination as normal healthy persons not having any systemic disorder. In this group of patients no clinically relevant abnormal laboratory results were found under the age of 60 years. In the group of 60 years and older a significant number had elevated serum creatinine values. PMID- 2586655 TI - [Investing in health care with Dekker as a guide]. PMID- 2586657 TI - [The diagnosis of a potentially malignant neck lymph node]. PMID- 2586656 TI - [African tick fever; fever, exanthema and skin ulcer]. PMID- 2586658 TI - [It is the tune which provides the diagnosis]. PMID- 2586660 TI - [Measuring of treatment effects in the individual patient]. PMID- 2586659 TI - [Diabetes education: striving for behavior change]. PMID- 2586661 TI - [Intracranial tuberculoma, a special space-occupying process]. AB - In four men and in one woman we found an intracranial local tuberculous infection (4 tuberculomas and 1 tuberculous abscess) in the period 1982-1988. Clinical presentation and computer tomography do not allow discrimination of intracranial tuberculomas from other space-occupying lesions. The value of the stereotactic biopsy for the diagnosis is emphasized and some characteristics of this intracranial process are discussed. PMID- 2586662 TI - [Acute rheumatism and glomerulonephritis; current clinical incidence and mortality in The Netherlands]. AB - The marked decline of morbidity and mortality of both rheumatic fever and acute glomerulonephritis reported in 1977 proves to have continued after 1975. After 1976, not a single death from rheumatic fever has been reported in The Netherlands, and in 1985-1987 only three deaths from acute glomerulonephritis were recorded. Nearly all European countries apart from the USSR, as well as Australia, Japan and New Zealand and North America report the same favourable trend, at any rate for rheumatic fever. Its possible causes are discussed. Some regional epidemiological rises in the US so far are no reason for alarm, although they do make it clear that it would be premature to speak of dying-out diseases. PMID- 2586663 TI - [Primary ciliary dyskinesia; a questionnaire study of the clinical aspects]. AB - With the aid of a questionnaire form we have gathered information about the clinical picture of patients suffering from primary ciliary dyskinesia. The study group numbered 34 persons, whose diagnosis was confirmed by electron microscopy. Chronic cough and common cold symptoms are present from shortly after birth. Twenty-three respondents reported respiratory tract problems in the neonatal period. The dysfunctional cilia result in chronic respiratory tract infections (chronic bronchitis; bronchiectasis; pneumonia; chronic sinusitis, rhinitis or otitis media). These lead to the following complaints: frequent blowing of the nose (in 32 pat.; 94%), chronic productive cough (in 28 pat.; 82%), chronic common cold (in 26 pat.; 77%), hearing problems (in 24 pat.; 71%), shortness of breath (in 23 pat.; 68%), frequent headache (in 13 pat.; 38%) and sore throat (in 9 pat.; 27%). In order to prevent the invalidating consequences of this disorder appropriate steps should be taken as soon as possible. These should include physiotherapy and adequate antibiotic therapy. PMID- 2586665 TI - [The 'historicity' of medicine: the forgotten chapter]. PMID- 2586664 TI - [The effect of admission to a geriatric department of a general hospital on drug consumption of the elderly]. AB - Admission to a geriatric department of a general hospital of 100 elderly patients admitted in succession, resulted in a slight decrease in number of the prescribed medication. The data were gathered retrospectively. Cardiovascular drugs accounted for the main decrease, sedatives and laxatives showed the highest increase. The use of diuretics is significantly associated with dehydration; 43% of the users of diuretics were dehydrated. The most striking conclusion was that 25% of the prescriptions could be stopped for lack of indication. PMID- 2586666 TI - [The future of primary health care]. PMID- 2586668 TI - [Regional differences in perinatal mortality: relationship with various aspects of perinatal care]. PMID- 2586667 TI - [Neurosis or psychosis: a formal distinction of practical importance]. PMID- 2586669 TI - [Exogenous factors and schizophrenia]. PMID- 2586670 TI - [How harmless is Toxocara?]. PMID- 2586671 TI - [Determination of fasting blood glucose and serum fructosamine levels for the assessment of glucose regulation in patients with non-insulin dependent diabetes mellitus]. PMID- 2586672 TI - [Liver metastasis: a death sentence?]. PMID- 2586673 TI - [Cystic fibrosis: a breakthrough in diagnosis, prevention and research]. PMID- 2586674 TI - [Organ and tissue transplantation in The Netherlands, possible or impossible?]. PMID- 2586675 TI - [Partial hepatectomy for benign or malignant liver diseases; experience in 94 patients]. AB - In this retrospective study, we analyse the results of 94 partial liver resections performed between 1972 and January 1989. The resections were performed for malignant (48 patients) and benign (46 patients) liver tumours. Nine patients (9.6%) died of resection-related complications. Mortality was significantly lower in the patients with resections for benign liver tumours (2.2%) compared with patients with resections for malignant liver tumours (16.7%) (p less than 0.05). In the patients who survived the first 30 days, complications occurred in 25.9%. The 5-year survival of patients with a primary malignant liver tumour (57%) is significantly (p = 0.05) better than in patients with a secondary malignant liver tumour (19%). From this study we conclude that partial liver resections for primary or secondary liver tumours can be performed with an acceptable mortality and morbidity, and should be the therapy of choice for selected patients. PMID- 2586677 TI - [Prevalence and risk factors of Chlamydia trachomatis infection in clients of a venereal disease clinic in Amsterdam]. AB - We studied the prevalence of Chlamydia trachomatis (CT) infection as well as its predictors among a sample (1000) of visitors (651 male, 349 female) of a clinic for sexually transmitted diseases (STD) in Amsterdam. The prevalence of CT was higher than that of gonorrhoea: among men, 14.3% and 11.5% and among women, 12.9% and 6.3% respectively. Independent predictors for CT infections were for men: number of leucocytes in discharge or urine, nature of urethral discharge, age and sex behavior, and in women: being warned as source or contact of a STD, age, nature of cervical discharge and bleeding from the cervical ostium after insertion of a swab. As many as 92% of the male and 81% of the female visitors of our STD clinic should be examined for CT if the presence of anyone or more of these predictors is taken as a criterion. Even then, 5% of the CT infections in women would still be missed. Based on our study results, material for the diagnosis of CT will from now on be collected routinely from all female patients of our STD clinic as well as from all males with urethritis. We advocate the expansion in the Netherlands of facilities for laboratory CT detection and its standard inclusion in STD examination. PMID- 2586676 TI - [HIV occupational risk of surgical specialists and operating room personnel in the Saint Lucas Hospital in Amsterdam]. AB - All instrument and needle accidents, and mucosal exposure to blood involving surgical specialists and operating room personnel were recorded for a seven-month period in a middle-sized Amsterdam hospital, the St. Lucas. Fifty-four accidents were reported, of which 42 were percutaneous wounds and 12, blood splatters in the eyes. The frequency of percutaneous wounds per operation per person ranged from 0 to 0.013. In the same period 3098 patients who had to be operated on were asked to participate in an anonymous study for HIV antibody. One hundred and twenty patients refused participation (3.9%). Of the 2978 participating patients seven were seropositive for anti-HIV (0.23%). The observed percutaneous accident frequency and HIV prevalence were used in combination with reports from the literature on the risk of infection after a single exposure to HIV infected material, to calculate the HIV professional risk for operating room personnel in this hospital. For general surgeons the risk of infection (based on 500 operations per year) was calculated as 0.0012 for an occupational lifespan of 30 years. For the other specialists and functions the risk was the same or less. Considering the low risk our conclusion is that screening of preoperative patients is not necessary in this hospital. The observance of general protective measures provides sufficient protection for the professional group examined. PMID- 2586678 TI - [Hypercalcemia in sarcoidosis]. AB - In a 56-year-old man hypercalcaemia and kidney function impairment were the presenting symptoms of sarcoidosis. The diagnosis was supported by the finding of elevated 1,25-dihydroxyvitamin D levels and of a cluster of epithelioid macrophages in aspirated bone marrow. By exclusion of other granulomatous diseases and a favourable reaction of the hypercalcaemia and renal function to treatment with prednisone the diagnosis was confirmed. The relationship between the autonomous extrarenal production of 1,25-dihydroxyvitamin D and the hypercalcaemia is discussed. PMID- 2586679 TI - [Screening for carrier state of the cystic fibrosis gene]. PMID- 2586681 TI - [The Central Bureau for Statistics: the burial place of our cases of death]. PMID- 2586680 TI - [Eurothemes. Luxury problems and the courage to set priorities]. PMID- 2586682 TI - [The treatment of stomach cancer: a light from the Far East]. PMID- 2586683 TI - Access to health information services in Nebraska. AB - The McGoogan Library of Medicine serves as Nebraska's vital link to health related information. According to Norman Cousins, "The library is not a shrine for the worship of books. It is not a temple where literary incense must be burned or where one's devotion to the bound book is expressed in ritual. A library, to modify the famous metaphor of Socrates, should be the delivery room for the birth of ideas--a place where history comes to life." PMID- 2586684 TI - Helping physicians access needed medical information: the Midcontinental Regional Medical Library Program. PMID- 2586685 TI - The management of the cleft lip and palate patient. AB - We believe that early closure of the hard palate defect with a palatal appliance and surgical closure of the lip and soft palate according to the rule of tens are very important. Delaying the hard palate closure allows for maximal growth of the palatal shelves. We also feel that pressure equalizing tubes placed in the ears at the initial surgical procedure allows for more normal function of the middle ear, less middle ear infections, better hearing, and ultimately better speech. We feel that early closure of the soft palate may decrease velopharyngeal incompetence by normalizing the position of the pterygoid plates. It may also help to reduce serous otitis media by improving eustachian tube function. PMID- 2586686 TI - "Cost containment or cost consciousness". PMID- 2586687 TI - [Disorders of body perception in schizophrenic psychosis. A case report]. PMID- 2586688 TI - [Cognitive deficits, vitamin status and controlled thiamine substitution in alcohol dependent patients in withdrawal treatment]. AB - Vitamin status and cognitive performance in a test battery were analyzed in 45 alcohol dependent men after admission to and after two weeks of withdrawal treatment in two psychiatric clinics. To examine the effect of thiamin substitution versus alcohol withdrawal and hospital diet alone, 23 patients received 300 mg thiamin daily, 22 patients no vitamin substitution. Thiamin substitution alone ameliorated selectively and significantly the mean marginal thiamin status. Multiple correlations between measurements of the thiamin parameter transketolase activity and test performances were found in the total study group. Thiamin substitution decreased the percentage of weak test performances, whereas the mean test performances did not differ significantly between experimental and control groups (limited in numbers). For clinical practice, thiamin substitution seems indicated during stationary withdrawal treatments, because there is no amelioration of the thiamin status with hospital diet and alcohol withdrawal alone, but there are possible correlations of thiamin deficiency and cognitive performances. PMID- 2586689 TI - [The significance of somatic and psychosocial factors for coping with illness by patients with multiple sclerosis]. AB - The coping behavior of 298 multiple sclerosis patients was assessed by means of a questionnaire. Despite more pronounced somatic complaints, women view their psychological situation more positively than men; they are more optimistic, less anxious, less depressed, and less preoccupied with their illness and its consequences. In the event of reduced working capacity due to the disease, men are more frequently disabled than housewives. However, there is evidence that early disability compensation may have a negative effect on the psychological well-being and the coping behavior. Careful thought should therefore be given to the timing when the question of a pension is discussed. PMID- 2586690 TI - [Stratification of psychopathologic syndromes. A case of paranoid development in multiple sclerosis]. PMID- 2586691 TI - [Rare intrasellar and suprasellar processes. 3: Vascular processes. Vascular lesions of the sella turcica]. PMID- 2586692 TI - [Computerized tomography and clinical findings in severe cerebral hypoxidoses. On the differential diagnosis of cerebral and extracerebral coma]. PMID- 2586693 TI - [Life-threatening encephalomyelitis in the 2d stage of Borrelia burgdorferi infection]. PMID- 2586694 TI - [The incidence of nosocomial infections in preventive administration of H2 receptor antagonists in neurology]. PMID- 2586695 TI - [Comments on the contribution by W. Weihe, A. Manke, W. Gowin, G. Mariss and F. L. Welter. The prognostic significance of lacunar lesions in magnetic resonance tomography in multiple sclerosis]. PMID- 2586696 TI - [Comments on the contribution of H.-H. v. Albert. A simple method for evaluating the corneal reflex]. PMID- 2586697 TI - Pre-morbid height and weight as risk factors for development of central nervous system neoplasms. AB - Information on pre-morbid height and weight from a national screening of tuberculosis between 1963 and 1975 was linked with the registrations in the population-based Norwegian Cancer Registry. For each case with a primary central nervous system (CNS) neoplasm, 10 matched controls were taken from the non-cases. Analyses were done by a Cox regression model for the total group of CNS neoplasms and the various histological groups. In the case of the total group, height emerged as a significant risk factor for both sexes. Within each sex, a similar trend was found for each histological group although statistical significance was retained only for glioblastoma among males and for other types of glioma (astrocytoma, oligodendroglioma, mixed glioma and ependymoma) for females. A significant negative association was revealed between Quetelet's index (weight/height squared) and 'other gliomas' in females. No association with body mass, as expressed by Quetelet's index, was found for patients with meningioma. PMID- 2586698 TI - Descriptive epidemiology of primary tumors of the brain, cranial nerves and cranial meninges in Los Angeles County. AB - This report presents data on the distribution of 8,612 cases of primary tumors of the brain, cranial nerves and cranial meninges (both benign and malignant) diagnosed among residents of Los Angeles County from 1972 to 1985. Incidence rates of gliomas, meningiomas, nerve sheath tumors and all histologic types combined are presented for specific age, sex and ethnic groups. At all ages, the highest incidence is seen for gliomas among men. Meningioma rates are higher among women than men in every ethnic group. In both sexes, glioma rates are highest among whites, and meningioma rates are highest among blacks. Asians have the lowest rates of both types of tumors. Proportional incidence ratios are elevated among those born in Eastern Europe, Southern Europe and the Middle East and among Jewish residents of Los Angeles County. A clear trend of increasing glioma incidence with increasing social class is seen among males. An analysis among white men aged 25-64 by occupation and industry at the time of diagnosis supports several previously published findings. A glioma excess is evident among workers in the aircraft industry. Workers in the petroleum industry and the rubber and plastics industry have an excess of meningiomas. Occupational groups at excess risk include dentists who have an increased risk of all types of brain tumors and electricians whose excess risk is limited to gliomas. PMID- 2586699 TI - Incidence and risk factors of Parkinson's disease in The Netherlands. AB - The incidence and some risk factors of Parkinson's disease were investigated in a study performed in The Netherlands. The study was based on a disease register of the Sentinel Stations, which provide a complete ascertainment of new patients with Parkinson's disease in 60 general practices in The Netherlands. The incidence rate of Parkinson's disease in The Netherlands is estimated to be 11/100,000 person-years for men and 12/100,000 person-years for women. Risk factors for Parkinson's disease were investigated in a case-control study in which 86 cases, with the diagnosis of Parkinson's disease confirmed by a neurologist, were compared with 172 reference subjects, matched for age and gender. Cigarette smoking was associated with a lower risk of Parkinson's disease (relative risk 0.6, 95% confidence interval 0.3-1.0). No association was observed between Parkinson's disease and severe head trauma with loss of consciousness, or surgery with total anaesthesia. PMID- 2586700 TI - Multifactorial inheritance and recurrence risks of multiple sclerosis in Italian patients. AB - This study is based on 166 patients with definite multiple sclerosis (MS) residing in different Italian regions and on 332 parents and 326 siblings. Seven patients had a first-degree relative with a definite diagnosis. The comparison with a population age-matched for specific frequency of MS showed an increase of the disease among relatives. The increase in MS frequency among sibs is compared with that expected under an autosomal dominant, autosomal recessive or multifactorial model. The multifactorial hypothesis appears to better fit the data. The heritability index is calculated for each combination of relative and affected patient sex and compared with estimates of other European and American countries. The recurrence risk rates for male and female relatives have been computed for the more frequent family situations. Our results support the hypothesis of a multifactorial model of inheritance and provide risk figures to be used in genetic counseling. PMID- 2586701 TI - Multiple sclerosis in relation to meat preservation in France and Switzerland. AB - In order to test a recent hypothesis on the possible role of defined agents from wood smoke in the etiology of multiple sclerosis (MS), the practices of meat preservation, as reported in ethnographic bibliography, were analyzed in relation to the MS distribution in France and Switzerland. In both countries, but more so in Switzerland, a significant association between both features could be demonstrated. PMID- 2586702 TI - Neurotraumatological survey in northern Israel. I. Annual and seasonal variations. AB - A descriptive epidemiological study of neurotraumatology was undertaken over a 4.5-year period at a regional hospital with a referral base of 1,200,000 residents with a single neurosurgical department. The 1,370 patients included in this study were those who required neurosurgical evaluation and treatment. The data base consists of demographic, clinical and radiological features at the time of admission, as well as the hospital course through to discharge. Higher admission rates were noted in spring and summer, although the mechanisms of injury showed variations. Some of the yearly variations can be explained, such as a change in rates of admission of soldiers and Lebanese population. A change from the expected outcome related to the Glasgow Coma Scale in one of the years deserves another quality control study. The main advantage of such a study, apart from the creation of data base, is an online guide for the decision-making process of health facility planning. PMID- 2586703 TI - [Clinical, CT and electrophysiologic studies of alcoholics with special reference to the cerebellum]. AB - Comprehensive clinical examinations and laboratory investigations were carried out in 20 alcoholics (Group III according to Jellinek's classification) with particular reference to the cerebellum. Clinical cerebellar signs were found in 4 cases, and in 3 of them atrophic changes of the cerebellum and cerebrum were demonstrated in CT examinations, and in 3 electrophysiological changes compatible with neuropathy were found. Evoked auditory potential from the brainstem was changed in 12 cases, which might be explained as impairment of the cerebellar function. In 12 cases signs of polyneuropathy were disclosed, in 5 of them they were evident clinically and electrophysiologically, and in 7 they were found only in EMG. Changes in somatosensory and visual evoked potentials were less evident, but in connection with abnormalities in other investigations they suggested presence of diffuse or disseminated nervous system damage. These investigations suggest that cerebellar signs in alcoholics are not isolated and are a manifestation of a more generalized damage to the nervous system. PMID- 2586704 TI - [Evaluation of reading and writing abilities and adaptation to school situations during the primary education period of children with early neonatal pathology]. AB - The study undertaken for assessment of the frequency of education difficulties and adaptation to school situation in elementary school is a continuation of previous studies on the frequency of neurological disturbances and psychomotor retardation in children with neurological abnormalities observed during the first days of life. In children with these early neurological abnormalities (n = 82) more frequent presence of educational difficulties and disturbances in adaptation to the situation in school were noted, in relation to controls (n = 84). PMID- 2586705 TI - [Conservative treatment of intracranial hematomas and the dynamics of their resorption]. AB - In 10 out of 63 patients with intracerebral haematomas treated conservatively the authors measured approximately the volume of haematomas by means of serial CT examinations during observation of their resorption. These were large and medium size haematomas, from 20 to 70 ml in volume. The mean rate of resorption was from 0.7 to 1.0 ml daily. Gradual regression of mass effects was noted. All patients were on admission in a relatively good condition, conscious or only somnolent, with focal neurological signs. In some cases signs of increased intracranial pressure were present. Improvement of the general condition and neurological status was relatively rapid, even pronounced paresis and aphasia regressed in most cases. Two patients (3%) died of non-cerebral causes. It is believed that most intracerebral haematomas may be treated conservatively. The presence of mass effects, increased intracranial pressure or even a major neurological syndrome are not regarded as indications to operation if the state of consciousness is good and is not deteriorating. Even large and deeply situated haematomas may be resorbed without leaving a gross neurological deficit. A careful observation of the state of the patient, control CT investigations and the possibility of carrying out emergency operation in case of deterioration of the level of consciousness are indispensable for safe conservative treatment of these patients. PMID- 2586706 TI - [Erdheim's tumors in adults--diagnosis, treatment and therapeutic results]. AB - The authors present a group of 27 adult patients aged over 25 years treated in the Department of Neurosurgery, Medical Academy in Warsaw in the years 1960-1985 for Erdheim's tumours. In most cases the first signs were visual disturbances and signs of raised intracranial pressure, and in only 48% of cases endocrine disturbances were additionally found. The basic diagnostic method in these cases was computerized tomography which indicates precisely the location of the lesion, its consistency and width of ventricles. All patients were treated surgically, the operative surgery was 14.8%. The authors believe that surgical treatment followed by radiotherapy is the best method of management of such tumours in adults. PMID- 2586707 TI - [Hoffmann's syndrome. The role of neurologists in the diagnosis of hypothyroidism]. AB - In a mason aged 48 years gradually hardness, rigidity and painful muscle spasms, slowness of movements and awkwardness with progressing difficulties in walking developed. Only after several months of observation the finding of pseudo myotonia suggested the diagnosis of Hoffmann's syndrome during hypothyroidism. In a number of neurological syndromes and in unclear muscular signs it is useful to consider hypothyroidism in the differential diagnosis. PMID- 2586708 TI - [Brain abscess complicated by suppurative meningitis in a patient with cyanotic heart defect. A case report]. AB - A case is reported of occipital lobe abscess complicated with purulent meningitis in a boy aged 16 years with Fallot's syndrome. The authors stress the necessity of taking into consideration the possibility of this complication in cases of congenital heart diseases and describe diagnostic difficulties due to scant signs of the abscess despite its large size. PMID- 2586709 TI - [Chronic intracranial hematoma]. AB - A case of chronic increasing intracerebral haematoma was observed in a man aged 47 years. PMID- 2586710 TI - [A case of multiple tuberculomas of the brain in a 17-year-old male]. AB - The authors describe a case of multiple intracerebral tuberculomas in a man aged 17 years. History data and results of investigations failed to suggest the presence of tuberculoma. The diagnosis was established after histological examination of a surgically removed lesion in the right occipital area. Intensive antituberculous treatment gave complete cure confirmed by CT examination. PMID- 2586711 TI - [Value of roentgen pictures in epilepsy]. PMID- 2586712 TI - [The experience of severe complication in the surgical treatment of chronic subdural hematoma: the usefulness of the burr hole and continuous closed system drainage]. AB - Seventy-four cases of chronic subdural hematoma were treated by burr hole with irrigation (31 cases), and burr hole and closed system drainage with slow decompression (43 cases). The postoperative changes of the clinical symptoms and CT findings in both groups were compared. Markwalder's clinical grading was used for evaluating the clinical symptoms. Preoperative grade distribution was as follows, 16 cases in grade 1, 12 cases in grade 2, 3 cases in grade 3 and no case in grade 4 in the irrigation group, and 22 cases in grade 1, 17 cases in grade 2, 3 cases in grade 3 and no case in grade 4 in the drainage group. There were two cases in the preoperative grade 2 which deteriorated after surgical decompression by burr hole with irrigation. One of them was considered due to brain swelling after abrupt decompression brought on by removal of the hematoma. This case was a 54-year-old male who lost consciousness during operation because of acute brain swelling. Severe neurological deficit such as speech disturbance and gait disturbance remained with him even three years after the operation. No case deteriorated in the drainage group. The postoperative improvement of the midline shift seen by CT scanning was of the same degree in both groups. Air accumulation in the subdural space was found in the irrigation group in all cases. However, it was found in only 5 cases in the drainage group. This study and available literature suggested that slow decompression should be carried out for all cases of chronic subdural hematoma, and we presented a closed system drainage as an example method. PMID- 2586714 TI - Pathological analyses on the compressed cord by the experimental spinal metastasis. AB - The purpose of the present experimental spinal metastasis developed in rats by inoculation of Walker's cancer cells through the spinous process is to find the factor which causes the initial damage of the cord in this disorder. In the early stage of paralysis, microangiogram exhibited that the degenerated posterior funiculus originated from the small hemorrhagic area in the posterior column of the involved cord. Scanning electron microscopic findings showed that the hemorrhage was of the intrinsic vein resulting from the disturbance of venous drainage in the compressed portion. In the early stage of compression, however, vascular permeability was observed in the white matter, but histologic degeneration was not. It was concluded that the trigger to induce the initial damage on the cord in spinal metastasis was likely to be the intrinsic venous hemorrhage. PMID- 2586713 TI - [Experimental analysis of intracerebral natural resistance against H-2+ and H-2- lymphomas grafted into the brain]. AB - The authors have investigated intracerebral natural resistance mechanism after tumor transplantation into the brain, by using YAC-1 (Moloney leukemia virus induced T cell lymphoma of A/Sn mouse origin) and its H-2 negative A. H-2-. It was found that highly immunogenic H-2+ YAC-1 was less tumorigenic than A. H-2- in untreated as well as NK-depleted syngeneic mice. The variant cells were not rejected even if inoculated together with YAC-1 cells into the brain. Furthermore, in T cell-depleted, thymectomized mice YAC-1 was as tumorigenic as A. H-2-. Thus, intracerebral natural resistance was expressed against YAC-1, suggesting that T cells but not NK cells might be involved in the tumor rejection with an MHC-restricted regulation. Contrary to this, A. H-2- cells escaped from the natural resistance of the brain. In vitro cytotoxicity assays showed that in relation to the enhancement of cell surface H-2 antigens, intracerebrally passaged YAC-1 cells decreased and increased the sensitivity to NK- and CTL mediated lysis, respectively. In contrast, A. H-2- did not alter either susceptibility to cell-mediated lysis or cell surface H-2 expression. In vivo rapid elimination assays revealed that after intravenous or subcutaneous inoculation there was a more efficient abrogation of 125I-iododeoxyuridine (IUdR) labelled YAC-1 cells in normal untreated mice compared to NK-depleted mice. After intracerebral inoculation, however, no difference in remaining radioactivity was observed between untreated and NK-depleted mice. This indicates that selective NK mediated elimination of tumor cells might occur after intravenous or subcutaneous but not after intracerebral inoculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2586715 TI - [Intrathecal perfusion of ACNU neurotoxicity and intrathecal pharmacokinetics in dogs]. AB - We studied the feasibility of intrathecal ACNU perfusion therapy against subarachnoid dissemination of malignant glioma. Intrathecal perfusion was performed in adult dogs by constant drip administration of 1 to 2 mg ACNU dissolved in 10 to 20 ml of lactate Ringer solution into the lateral ventricle and cerebrospinal fluid drainage through the lumbar puncture. The perfusion time was changed from 15 to 71 min. A bolus injection of 2 mg ACNU was also tested in one dog. No neurological symptom was noted during and after perfusion, and histological examination reveal only a minimum denudation of ependyma in a small area. Concentration of ACNU in CSF and serum were measured by HPLC (high performance liquid chromatography). ACNU was detected in lumbar CSF only by perfusion, not by bolus injection, and the maximum concentrations were 6.26 to 25.76 micrograms/ml. The elimination phase of ACNU in lumbar CSF followed linear kinetics and the half-time was 18 min on average. AUCs (area under the drug concentration-time curve) were 346 to 896 micrograms.min/ml and they were the equivalent of in vitro cell kills in excess of 3 logs for rat 9L gliosarcoma and human glioma 126 cells. Serum concentration was 0.10 micrograms/ml in maximum. These findings suggest the feasibility of intrathecal ACNU perfusion therapy against subarachnoid dissemination of malignant glioma and warrant further studies. PMID- 2586716 TI - [A case of posttraumatic cerebral air embolism]. AB - We report a case of cerebral air embolism that occurred after chest trauma. The diagnosis was confirmed by CT and skull roentgenogram which demonstrated air bubbles in intracranial arteries. It is well recognized that cerebral air embolism is caused by various diagnostic and therapeutic procedures, and trauma. But it may often be overlooked because it is diagnosed clinically and there are no characteristic symptoms nor signs. Although various ways of treatment have been reported, prevention and early diagnosis are the most important. It is very rare that air bubbles are detected in skull roentgenograms in cases of cerebral air embolism. Only three other cases have been reported. One of these cases reported by Westcott awakens our interest because the patient died within only several minutes after the onset and underwent cardiac massage before the roentgenogram was taken, in the same way as our case. We think some artificial force is necessary to push air into intracranial arteries to the extent that it is detected on a skull roentgenogram. Little has been reported on CT findings in cerebral air embolism. Roughly speaking, three kinds of abnormal findings have been reported. They are air, edema, and infarction. In only nine cases including ours, air bubbles were detected on CT. In those cases CT scans were performed soon after the onset, twelve hours at the latest. Abnormal findings were detected in either bilateral hemispheres or in the right hemisphere only. Almost all lesions are located in the territory of the cortical branches, but in one case bilateral, thalamic infarction was noted, which is thought to be caused by embolism of thalamoperforators.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2586717 TI - [Chronic subdural hematoma following advanced cancer: report of three cases]. AB - Three cases of chronic subdural hematoma (CSH) following advanced cancer are reported. Case 1. A 54-year-old male patient was referred to our clinic in a semicomatose state. Bilateral CSH was evacuated through a pair of burr holes, and consciousness was recovered. However, subependymal hemorrhage occurred at the third ventricle 6 days after the operation. Hematological examination revealed thrombocytopenia. He died 12 days after operation because of hemorrhage in the lung. Postmortem examination disclosed metastatic adenocarcinoma of unknown origin to the dura mater, lymph nodes, lung and bone marrow. Case 2. A 50-year old male patient who was diagnosed as having gastric cancer was referred to our clinic in a state of deep coma. CT scan revealed CSH and putaminal hemorrhage at the left side. Hematological examination revealed disseminated intravascular coagulation (DIC). After the subdural hematoma was evacuated, the putaminal hematoma enlarged and hemorrhagic infarction at the left temporo-occipital lobes occurred. He died 2 days after operation. Autopsy was not carried out, but histological examination revealed poorly differentiated malignant cells in the outer membrane of the subdural hematoma. Case 3. A 53-year-old female patient who had a history of gastric cancer operated on 4 years ago was admitted to our clinic complaining of headache and vomiting. CT scan revealed bilateral subdural hematoma. Following a pair of burr-holes and irrigation of the hematoma, hemorrhage recurred alternatively at the left side on the 6th and at the right side on the 27th day after the operation. Hematological examination revealed DIC, and bone marrow puncture disclosed metastasis of the adenocarcinoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2586718 TI - [Bilateral pericallosal artery aneurysms in a mirror position]. AB - A rare case of ruptured pericallosal (distal anterior cerebral) artery aneurysm, associated with another one in a mirror position is reported in this paper. The angiograms disclosed no variant vessels, such as azygos anterior cerebral artery and/or supreme anterior communicating artery. This patient, a 47-year-old woman, was successfully treated by surgery without any complication. The literature concerned is reviewed and possible pathogenesis of cerebral aneurysm discussed briefly. PMID- 2586719 TI - An immunohistochemical characterization of the primitive and maturing neuroepithelial components in the OTT-6050 transplantable mouse teratoma. AB - The neuroepithelial component of the OTT-6050 mouse teratoma has previously been characterized as an experimental system for the study of differentiation and cytologic maturation in embryonal tumours of the human central nervous system. A number of transplantable tumours composed of primitive stem cells and of a neuroepithelial component displaying a spectrum of differentiation were previously produced by centrifugal elutriation of the dissociated OTT-6050 teratoma. These tumours have provided a reproducible cell population that has permitted the study of both the early and later stages of neoplastic neurocytogenesis. The purpose of the present study was to detect, by immunohistochemistry, the earliest stages of neurocytogenesis in these tumours as shown by the expression of neuron-associated microtubule proteins. This was correlated to the appearance and localization of other markers associated with neuronal and glial differentiation. The primitive neuroepithelial structures resembling neural tubes (medulloepithelial rosettes) contained single or small groups of cells which reacted with the monoclonal antibody TUJ1, specific for the neuron-associated class III beta-tubulin isotype. Immature neuroblasts and maturing polar neurons also showed immunoreactivity with TUJ1, whereas reactivity for microtubule-associated protein 2 (MAP2), tau, the 200 kilodalton isoform of neurofilament protein, neuron-specific enolase and synaptophysin was primarily seen in maturing neurons. By comparison, both medulloepithelial and ependymoblastic rosettes, neuroblasts and glial cells were immunopositive with monoclonal antibody TU27, which defines an antigenic site shared by most mammalian beta-tubulin isotypes. Astroglia were reactive with antisera to glial fibrillary acidic and S-100 proteins, but not with monoclonal antibody (MAb) TUJ1, or with MAbs to the other neuron-associated cytoskeletal proteins, MAP2, tau and the 200 kilodalton subunit of neurofilament protein. Our findings suggest that (1) expression of the class III beta-tubulin isotype is an early event during neoplastic neurocytogenesis, (2) this isotype is subsequently preserved in maturing neuronal populations, and (3) it is not present at detectable levels in stem cells or glial cells. The observation that morphologically undifferentiated neuroepithelial cells express a neuron-associated beta-tubulin isotype signifies the value of examining tubulin isotype expression in the characterization of normal and neoplastic neuroepithelial differentiation. PMID- 2586721 TI - Spontaneous recovery from the encephalomyelitis in mice caused by street rabies virus. AB - Recovery from rabies was studied in an experimental model. Young adult mice were inoculated in a hindlimb footpad with street rabies virus (fox salivary gland isolate). In a group of 62 mice, 97% developed clinical rabies with paresis of the extremities and spasticity, and 37% recovered with neurological sequelae. There was an acute inflammatory reaction in the brainstem and grey matter of the spinal cord, and degeneration of myelinated axons in the white matter of the cord and in the dorsal roots. Rabies virus antigen was found in the central nervous system of all mice examined between day 5 and 13, and also in trigeminal and dorsal root ganglia. Surviving mice had neutralizing antibodies in serum and brain tissue, and 90% survived an intracerebral challenge with the CVS strain of fixed rabies virus. Spontaneous recovery from rabies encephalomyelitis was demonstrated with evidence of viral replication and pathological changes in the central nervous system. PMID- 2586720 TI - Reversible neuronal damage in hippocampal pyramidal cells with triethyllead: the role of astrocytes. AB - A single dose (19 mg kg-1) of triethyllead given to weanling rats produces necrosis in a small number of hippocampal pyramidal (CA3) and hilar neurons with reversible changes in the remaining neurons of this region. The sequence of events has been studied by light and electron microscopy over a period from 12 h to 14 days after dosing. Early changes resemble those previously described for trimethyltin, with the formation of characteristic tubulo-vesicular dense bodies by 12 h accompanied by vacuolation of Golgi and smooth surfaced endoplasmic reticulum (SER) elements which became generalized by 24 h. Large numbers of secondary dense bodies, formed from tubulo-vesicular dense bodies as well as from autophagosomes, were present by 48 h, whilst very little rough surfaced endoplasmic reticulum (RER) and few polyribosomes remained and vacuolation was much reduced. In those animals which did not die from seizures, the majority of hippocampal pyramidal cells were able to recover from these changes with astrocytes playing a significant role in the elimination of the dense bodies. This involved astrocytes inserting processes into the neuronal perikaryon from where the secondary dense bodies were selectively transferred into the astrocyte cytoplasm. This activity was first seen at 48 h, reached a peak at 4 days, when most CA3 neurons contained one or more astroglial intrusions and subsided soon after. The surviving neurons returned to apparent normality over the period from 3 to 7 days with a gradual return of polyribosomes. Golgi elements and RER. PMID- 2586722 TI - Experimental intracerebral haematoma in the rat: sequential light microscopical changes. AB - In a small animal model of controlled intracerebral haemorrhage, changes within the haematoma and surrounding tissues were examined by light microscopy in toluidine blue stained semithin sections. Groups of animals were killed at 2, 6, 15, 24 and 48 hours, 2, 4, 8 and 14 days, and 3 months survival. Sequential changes in neurons, glia and leucocytes, together with the gradual absorption of the blood clot and its replacement by an astrocytic scar are described. PMID- 2586723 TI - Hemangioblastomas: clinical and histopathological factors correlated with recurrence. AB - Although hemangioblastomas are regarded as benign neoplasms, they may recur in up to 25% of cases. The clinicopathological correlates of this more aggressive behavior have not been identified. Among 26 patients with hemangioblastomas who had been evaluated and treated at the Massachusetts General Hospital between 1974 and 1986, 7 (27%) developed recurrences after surgical extirpation. Recurrence was correlated with younger age, that is less than 30 years at the time of diagnosis (P less than 0.01), von Hippel-Lindau syndrome (P less than 0.001), and the presence of multicentric tumors of the central nervous system at initial diagnosis (P less than 0.005). Histopathologically, recurring hemangioblastomas had lower frequencies of cyst formation (P = 0.10) and lower proportions of lipid laden stromal cells (P less than 0.05). The findings suggest that a particular constellation of clinical and pathological features can be used to predict the likelihood of recurrence of a hemangioblastoma, and therefore to identify patients in need of long-term follow-up or, possibly adjunctive therapy. PMID- 2586724 TI - Surgical management of hemangioblastoma of the spinal cord: a report of 18 cases. AB - The cases of 18 patients operated on for hemangioblastoma of the spinal cord were reviewed. There were 11 men and 7 women. (M:F = 1.6:1) and in 15 patients, the onset of spinal symptoms was before the age of 40 years. There were 19 intradural and 2 extradural tumors. The tumor was accompanied by a cyst in 9 patients (50%). There were 6 cases of Lindau's disease, including 3 cases of multiple spinal tumors. Symptoms improved postoperatively in 13 patients. were unchanged in 2, and were aggravated in 3. At the present time, magnetic resonance imaging with gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA) enhancement is the most useful tool for precise localization of the tumor and differentiation of any accompanying cyst. PMID- 2586725 TI - Effect of intracerebrally injected Corynebacterium parvum on the development and growth of metastatic brain tumor in mice. AB - Using KHT tumor in a mouse metastatic tumor model, we examined the effect of intracerebral and/or intraperitoneal injections of Corynebacterium parvum on the growth of metastatic brain tumor and the development of an inflammatory response in the central nervous system (CNS). C. parvum given intraperitoneally had no effect on the development and growth of CNS tumor, but did prolong the survival of mice by inhibiting the growth of systemic metastatic tumor, which was the cause of death in our tumor model. Mice that received intracerebral injections of C. parvum exhibited significantly decreased growth of metastatic brain tumor, as compared with mice that received intracerebral injections of saline, whether or not they had received C. parvum intraperitoneally. In addition, the brains of mice that received C. parvum intracerebrally exhibited an inflammatory response that was minimal or absent in the brains of control mice. Our results suggest that if immunotherapeutic agents can be delivered to the CNS and cause an inflammatory response, they can be effective against CNS metastases. PMID- 2586726 TI - [11C]L-methionine uptake in gliomas. AB - Treatment of gliomas remains disappointing in spite of a great number of experimental biological data and of randomized therapeutic studies. This could be partly explained by the inefficiency of our conventional methods to assess the regional metabolism of these tumors. The use of positron emission tomography (PET) brings encouraging possibilities in this field. We report our preliminary experience of measuring regional cerebral methionine uptake with PET after intravenous injection of [11C]L-methionine. Twenty-two patients with histologically confirmed gliomas were studied. An ECAT II positron emission tomograph was used for scanning. The position of the plane was chosen to include a major section of the tumor in the reconstructed brain slice. The protocol required a two-step examination: 1) after injection of 15 to 25 mCi of [11C]L methionine, 12 scans were performed over a period of 46 minutes; and 2) 18 hours later, regional cerebral blood volume was measured in the same slice after intravenous injection of 2 to 4 mCi of 68GaCl3. The tumoral region of interest was determined as being the area of maximum activity. For each patient we calculated the ratio, R, between the activity in this tumor region of interest and the activity in the contralateral healthy symmetric region of interest which was used as an "internal standard" for the same patient. We correlated the ratio R with the histological grading. In 22 patients, mean values of R were calculated for each tumor: Grade II (n = 5): R = 1.04 +/- 0.27; Grade III (n = 5): R = 1.68 +/- 0.22; and Grade IV (n = 12): R = 2.33 +/- 0.86.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2586727 TI - Arterial wall changes in cerebral vasospasm. AB - A right-sided subarachnoid hemorrhage (SAH) was created in 12 monkeys. Only the right (clot-side) cerebral arteries developed angiographic vasospasm (VSP), which was maximal 7 days after SAH. Eight animals were killed at this time and the remainder at 14 days. At the time of killing the middle cerebral arteries (MCAs) were harvested, and four normal, left (non-clot-side) MCAs were vasoconstricted in vitro with prostaglandin F2 alpha. All MCAs were studied with scanning and transmission electron microscopy. Right MCAs in maximal VSP 7 days from SAH were undistinguishable on scanning electron microscopy from normal arteries vasoconstricted in vitro: both groups demonstrated a mean 57% reduction in vessel caliber and a 5-fold increase in vessel wall thickness compared to normal, nonvasoconstricted left MCAs. On transmission electron microscopy, however, arteries in SAH-induced VSP showed degenerative changes in the tunica intima and media. These changes were still evident at 14 days, despite considerable resolution of VSP. These findings, as well as those from other pathological studies of animal and human cerebral arteries in VSP, suggest that the arterial narrowing and vessel wall thickening seen within several weeks of SAH is due primarily to medial contraction, but unlike simple vasoconstriction, is associated with degenerative ultrastructural changes in the endothelium and vascular smooth muscle cells which may denote a temporarily irreversible state. PMID- 2586728 TI - Impairement of vascular reactivity and changes in intracellular calcium and calmodulin levels of smooth muscle cells in canine basilar arteries after subarachnoid hemorrhage. AB - We examined vascular reactivity to various vasoconstrictors and dilators, and the changes in calcium-calmodulin levels in canine basilar arteries after subarachnoid hemorrhage (SAH). Contractile responses to noradrenaline, serotonin, and potassium chloride were markedly attenuated at 48 hours (P less than 0.05), and further attenuated at 7 and 14 days after SAH (P less than 0.01). Dilation responses to calcium antagonist were maintained at 48 hours after SAH, but were markedly reduced at 7 and 14 days after SAH (P less than 0.05). Transmission electron micrographs of the basilar artery showed contraction of the media between 48 hours and 7 days and degeneration of smooth muscle cells over the 7 days after SAH. Electron microscopic cytochemical examination for calcium showed that intracellular deposits of calcium pyroantimonate increased in smooth muscle cells of basilar arteries at 1 hour after the first intracisternal injection of blood (early spasm), but decreased in smooth muscle cells at 48 hours after SAH (at the beginning of delayed vasospasm). They decreased further in the vessels 7 days after SAH. The calmodulin contents in the basilar arteries were decreased slightly at 6 hours, and significantly (P less than 0.05) at 48 hours after SAH, as determined by radioimmunoassay and phosphodiesterase assay. Therefore, it is considered that delayed vasospasm is not simply an active contraction of the vessels, but a functional or structural derangement of contractile elements of smooth muscle cells after 48 hours after SAH. PMID- 2586729 TI - Neurogenic pulmonary edema in the acute stage of hemorrhagic cerebrovascular disease. AB - Extravascular lung water (EVLW) was measured by the double-indicator dilution method in 25 patients with hemorrhagic cerebrovascular diseases. EVLW had a significantly positive correlation with both alveolar-arterial oxygen difference (AaDO2) and intrapulmonary shunt. The value of EVLW in the acute stage in 15 patients with increased AaDO2 more than 20 mm Hg was 7.8 +/- 2.2 ml/kg and that in the chronic stage 4 weeks after onset significantly decreased to 4.6 +/- 0.7 ml/kg (P less than 0.001). The value of EVLW in the acute stage in 10 patients with normal AaDO2 less than 20 mm Hg was 4.7 +/- 1.1 ml/kg and that in the chronic stage 4 weeks after onset was 4.5 +/- 0.2 ml/kg. There was no significant difference between them. Pulmonary arterial blood pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac index, systemic vascular resistance index, and pulmonary vascular resistance index in the acute stage in the 25 patients were all within the normal range. Three patients with neurogenic pulmonary edema had markedly increased EVLW without abnormalities in pulmonary arterial blood pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac index, systemic vascular resistance index, and pulmonary vascular resistance index. From these facts, the main cause of the increase in EVLW cannot be explained by left ventricular failure, but can be explained by high permeability pulmonary edema. PMID- 2586731 TI - Zygomatic temporopolar approach for basilar artery aneurysms. AB - For surgery of upper basilar artery aneurysms, we have modified the temporopolar approach proposed by Sano by detaching the zygomatic arch to obtain a wide, shallow operating field. This approach seems to be suitable for anteriorly protruding, high-positioned, or large aneurysms of the upper basilar artery. We have used this zygomatic temporopolar approach in 4 patients with such aneurysms and obtained satisfactory results. In this paper, we detail the operative procedure and emphasize certain technical points to minimize temporal lobe retraction and to prevent oculomotor and facial nerve injuries. PMID- 2586730 TI - Brain mapping techniques to maximize resection, safety, and seizure control in children with brain tumors. AB - Intraoperative brain mapping techniques were used to localize language cortex, sensorimotor pathways, and seizure foci in children with supratentorial brain tumors. The methods of direct cortical and subcortical stimulation, in addition to electrocorticography, enabled us to maximize tumor resection, minimize morbidity, and eradicate epileptogenic zones which were always adjacent to, but not involving, the tumor nidus. Language localization was found to be quite variable in the children tested and anatomically unpredictable based on the preoperative neurological or radiological examination. Physiological mapping techniques, therefore, appear to be safe, reliable, and very useful for operations on tumors located within or adjacent to eloquent brain regions in the pediatric population. PMID- 2586732 TI - Zygomatic approach for resection of mesial temporal epileptic focus. AB - By using the zygomatic approach, temporal mesial and polar epileptic foci are easily accessible through an incision in the inferior temporal gyrus. In this approach, a major part of the superior and middle temporal gyrus is preserved, and there is no risk of postoperative dysnomia even on the dominant side for speech. Combined use of depth and subdural electrodes is advisable for precise determination of focus distributions throughout the mesial and lateral structures of the temporal lobe. We have applied this approach in 5 patients with satisfactory results. PMID- 2586733 TI - Gamma knife surgery for recurrent solitary metastasis of a cerebral hypernephroma: case report. AB - Gamma knife surgery employing a central dose of 70 Gy and a peripheral dose of 25 Gy caused progressive necrosis and shrinkage of a recurrent solitary metastasis of a cerebral hypernephroma, as verified by computed tomographic scan 2 and 4 months after treatment. Gamma knife surgery was an effective palliative treatment for this cerebral metastasis and was an alternative to craniotomy with microsurgical removal. PMID- 2586734 TI - Sterile abscesses in glioma patients treated by intraparenchymal injection of lymphokine-activated killer cells and recombinant interleukin-2: case reports. AB - Earlier, we conducted Phase I clinical trials to determine any acute toxicity of adoptive immunotherapy with intralesional injections of autologous lymphocytes expressing lymphokine-activated killer (LAK) activity and recombinant interleukin 2 (rIL-2) in patients with malignant glioma. Within six weeks of craniotomy and intralesional injection of autologous LAK cells plus rIL-2, 3 of 29 patients demonstrated a decline in clinical status and evidence on computed tomographic and magnetic resonance imaging scans of edema and mass of unknown character at the site of previous surgery and immunotherapy. Craniotomy was performed to remove the tissue and reduce intracranial pressure. Microscopic examination of the excised material indicated no new tumor growth within the resected mass, but rather that the tissue had the histological characteristics of a chronic sterile abscess including necrosis, fibrosis, and influx of inflammatory cells. Factors that may have contributed to this reaction in the 3 patients were age, Karnofsky score, the extent of tumor excision, and immune status. All 3 had also been treated with greater than average numbers of rIL-2 activated lymphocytes that demonstrated significant in vitro LAK activity. The results suggest that in patients whose clinical status is good and who are not immunosuppressed by corticosteroids, the dose-limiting toxicity of intraparenchymal immunotherapy with LAK cells plus rIL-2 for glioma may be related to the total, absolute number of activated cells injected, and this toxicity develops over time and is manifested by development of a sterile abscess. PMID- 2586736 TI - Vertex epidural hematomas. AB - Four cases of vertex epidural hematomas are presented to illustrate the unique management problems which set them apart from their more common counterparts located over the temporal convexity. Diagnosis requires a high degree of suspicion as vertex epidural hematomas are often missed by conventional horizontal scanning. Coronal computed tomographic scanning should be undertaken in all suspected cases. Clinical symptoms exceeding the small volume of clot may be present due to venous obstruction and disruption of cerebrospinal fluid absorption. Evacuation of the clot usually leads to clinical improvement. PMID- 2586735 TI - Recovery of gonadal function after resection of an oligodendroglioma localized in the anterior horn of the lateral ventricle: relation to pulsatile secretion of luteinizing hormone. AB - A 21-year-old man with an oligodendroglioma in the anterior horn of the right lateral ventricle complained of sexual dysfunction and showed lowered concentrations of serum testosterone (1.1 ng/ml) with normal pituitary function. Human chorionic gonadotropin testing revealed a good testosterone response (1.1 to 4.9 ng/ml) and a clomiphene test revealed no gonadotropin response. Pulsatile secretion of luteinizing hormone (LH) was absent preoperatively. After removal of the tumor, serum concentration of testosterone increased to the normal range, LH pulsatility appeared, and the patient had no complaints of sexual dysfunction. In this patient, the loss of LH pulsatility responsible for his hypogonadism was caused by the lateral ventricle tumor compressing the surrounding structures, and this was corrected by tumor resection. PMID- 2586737 TI - Bilateral extradural hematomas in a thrombocytopenic infant receiving anticoagulants: case report. AB - A unique case of bilateral extradural hematomas in an infant is reported. Relevant aspects of the patient's history, including the absence of any known trauma and the presence of an underlying coagulopathy are discussed. The radiographic and operative findings of this case are presented, and an explanation of the mechanism of the hematomas is offered. PMID- 2586738 TI - Calvarial tuberculosis: a report of two cases. AB - Two cases of calvarial tuberculosis associated with neurological involvement are presented. The radiological features and therapeutic management are discussed and the literature is reviewed. PMID- 2586739 TI - Extrusion of a Raimondi peritoneal catheter from the thigh. AB - A case of extrusion of a peritoneal shunt catheter from the thigh is reported. The literature is reviewed and the frequent involvement of Raimondi catheters in extrusion is discussed. PMID- 2586740 TI - Isolated injection injury to the posterior femoral cutaneous nerve. AB - The sciatic nerve is by far the most common nerve accidentally injured during intramuscular injection. Despite its close proximity to the sciatic nerve, however, injury to the posterior femoral cutaneous nerve is apparently quite rare. In this report, clinical features of a patient with isolated injection injury to the posterior femoral cutaneous nerve are described. PMID- 2586742 TI - Our future neurosurgical leaders: who will they be? PMID- 2586741 TI - Anterior screw fixation of odontoid fractures. PMID- 2586743 TI - Intrahippocampal grafts of fetal basal forebrain tissue alter place fields in the hippocampus of rats with fimbria-fornix lesions. AB - Intrahippocampal grafts of fetal basal forebrain tissue have been shown to restore several aspects of neural function, including some degree of behavioral recovery in spatial memory tasks, in rats with fimbria-fornix lesions. Place fields, the behavioral correlates of complex-spike unit activity recorded in the hippocampus of rats, are altered by fimbria-fornix lesions, and provide an important measure of the functioning circuitry of the hippocampus after grafts. To investigate the effects of grafts on hippocampal circuitry, complex-spike units were recorded while the rats traversed a radial maze. Quantitative analyses of spatial activity showed that units in normal rats had spatially clustered, reliable place fields that were stable despite alterations of the maze. In contrast, units in rats with fimbria-fornix lesions had more dispersed, less reliable place fields that were disrupted when the maze was covered or rotated. Compared to rats with fimbria-fornix lesions, rats with grafts and units with more tightly clustered, more reliable, and more stable place fields when the maze was altered. The results suggest that: (1) fimbria-fornix lesions disrupt some aspects of complex-spike place field activity; (2) the functioning of hippocampal circuitry is influenced by fetal basal forebrain grafts; and (3) the grafts may ameliorate the effects of lesions on spatial behaviors by influencing critical aspects of place field activity in the hippocampus. PMID- 2586744 TI - Development of early swimming in Xenopus laevis embryos: myotomal musculature, its innervation and activation. AB - The development of the axial musculature, its innervation and early locomotion in Xenopus laevis embryos are described. Between stages 17 and 40 some 45 myotomes are formed on each side of the body. During this period the animals develop from non-motile to free swimming embryos. Using fluorescein-conjugated bungarotoxin the acquisition of acetylcholine receptor-sites was studied. At stage 25 (early flexure stage) bound bungarotoxin was confined to the first seven intermyotomal clefts, in free swimming embryos (stage 33) to the first 20 clefts. Application of horseradish peroxidase to the intermyotomal clefts in embryos ranging from stages 25 to 37/38 revealed that primary motoneurons were usually situated 100 400 microns, i.e. 0.5-1.5 myotomes, rostral to the cleft they innervated. The motor axons left the spinal cord at the caudal side of each spinal segment where neural crest was present between the cord and the myotomes. At stage 25 ventral root activity could be recorded extracellularly from only the first three intermyotomal clefts, at stage 32/33 from the first 16 clefts. The first spontaneous rhythmic swimming-like activity could be recorded around stage 28. Between stages 27 and 32/33 the initial swimming frequency and the swimming episode duration increased at least three-fold. Comparable results were obtained with high-speed cinematography and measurements with a photoelectric transducer. Between stages 17 and 40 the number of myotomes increased by 0.9 myotome h, approximately 11.4 h later followed by the innervation of the myotomes at 0.7 cleft/h. About 3.6 h after this, ventral root activity appeared at the rate of 0.6 cleft h. This study shows that the early swimming pattern generating neuronal network, located within the rostral spinal cord, reaches a state of "critical mass" around stage 27, at which the first rhythmic swimming activity occurs. At least 6-10 functional spinal segments and adjacent myotomes are required for early swimming. PMID- 2586745 TI - Development of the hypothalamic 5-hydroxytryptamine system during ontogenesis in rats: uptake and release of 5-hydroxytryptamine in vitro. AB - The development of the hypothalamic 5-hydroxytryptamine system has been evaluated in vitro according to [3H]5-hydroxytryptamine uptake and release in fetuses (16 20th fetal day), neonates (9th postnatal day) and adults (45th day of life). At the 16th fetal day the hypothalamic neural elements were characterized by specific uptake of 5-hydroxytryptamine and its spontaneous release; the next day K+-stimulated Ca2+-dependent release appeared. By the 18th fetal day, the 5 hydroxytryptamine uptake doubled and was retained at this level both in older fetuses and in postnatal rats. The K+-stimulated release of [3H]5 hydroxytryptamine increased considerably during the perinatal period, reaching an adult level by the 9th postnatal day. These data indicate the sprouting of 5 hydroxytryptamine fibers to the hypothalamus and the maturation of their membrane mechanisms for the bidirectional transport of 5-hydroxytryptamine early during ontogenesis-to a significant extent before the 18th fetal day. PMID- 2586747 TI - A quantitative study of the projections of the gracile, cuneate and trigeminal nuclei and of the medullary reticular formation to the thalamus in the rat. AB - Following injection of horseradish peroxidase into the thalamus of one side, the numbers of labelled neurons in the nuclei of the dorsal funiculi and in the trigeminal sensory complex were counted. A comparative study was made of the pattern of labelling after a range of survival times, and animals surviving for 72 h after injection were used to provide detailed quantitative information about the patterns of distribution of labelled cells. The principal sensory nucleus of the trigeminal nerve (8683 labelled neurons) and the nucleus of the spinal trigeminal tract, pars interpolaris (1920) label heavily after thalamic injection. Pars oralis of the spinal nucleus labels more sparsely (524 labelled neurons), while the pars caudalis (260 labelled neurons) shows a laminar labelling pattern which continues across the spinomedullary junction into the upper cervical segments. The gracile (2152 labelled neurons) and cuneate (2339) nuclei also show rostrocaudal variation in labelling density: the middle one third of each nucleus contains 66% of labelled gracile and cuneate cells. The findings are correlated with known features of the arrangement of the ascending sensory projections from these nuclei in various species, and are compared with previous findings on the distribution of thalamically-projecting cells in the upper cervical segments of the spinal cord. PMID- 2586746 TI - Rapid maturation of synaptic functions of prenatal serotoninergic neurons in short-term cultures: absence of sex differences and hormone effects. AB - Serotonin is believed to modulate neuronal differentiation during early stages of brain development. In order to assess basic functional requirements for such a role, it was investigated how early serotoninergic neurons mature with respect to transmitter storage and stimulus-secretion coupling. Dissociated cell cultures were raised from embryonic rat rhombencephalon obtained at gestational day 14 and cultured for 3-8 days, which may roughly correspond to the prenatal period in vivo. Because of a possible involvement of serotonin in processes leading to sexual differentiation of the brain, gender-specific cultures were raised in addition and treated with sex steroids. Sensitivity of [3H]serotonin uptake to fluoxetine could already be observed at 3 days in vitro. Vesicular storage as probed with reserpine and nigericin, and the capability of releasing preaccumulated serotonin in a Ca2+-dependent manner were also present as early as 3 days in vitro. Seven per cent of the pre-accumulated transmitter could be released per minute upon stimulation with 54 mM K+. Immunocytochemical and autoradiographic preparations demonstrated that, after the same short culture period, the neurons had formed large fiber networks. No differences could be detected regarding any of the above parameters between female and male serotonin neurons and between cultures treated with and without estradiol, testosterone and dihydrotestosterone. It is concluded that, in contrast to other neuronal phenotypes, serotoninergic neurons are functionally mature when or shortly after they are taken into culture, i.e. around gestational day 14. The functional competence of prenatal serotonin systems should be a prerequisite for their suspected role in modulating neural development at pre and postsynaptic sites. The present results provide no evidence for the occurrence of a sexual dimorphism of serotonin neurons at this early developmental stage. PMID- 2586748 TI - Visceral and somatic afferent origin of calcitonin gene-related peptide immunoreactivity in the lower thoracic spinal cord of the rat. AB - The origin of calcitonin gene-related peptide in the thoracic spinal cord of the rat was investigated by radioimmunoassay and immunohistochemistry. In transverse sections from normal animals there was a dense staining of calcitonin gene related peptide-immunoreactivity in laminae I, II and V of the dorsal horn. In parasagittal sections this was found to consist of rostrocaudally orientated fibres in laminae I and II and longitudinal bundles of fibres interspersed with a plexus of immunoreactivity in lamina V. After sectioning the thoracic spinal nerves there was a significant reduction in immunoreactivity in the dorsal horn of the spinal cord which was seen as a marked reduction of staining in lamina II and in the bundles of fibres in lamina V. Section of the splanchnic nerve slightly reduced staining in lamina I and virtually abolished the plexuses of immunoreactivity in lamina V. However, measurement of calcitonin gene-related peptide in samples from coeliac-ganglionized rats revealed an increase in immunoreactivity in regions of the spinal cord containing lamina V. These results provide evidence of a visceral and somatic afferent origin of calcitonin gene related peptide in the thoracic spinal cord of the rat. PMID- 2586749 TI - Lever pressing for food reward and in vivo voltammetry: evidence for increases in extracellular homovanillic acid, the dopamine metabolite, and uric acid in the rat caudate nucleus. AB - Linear sweep voltammetry at chronically implanted carbon paste electrodes was used to study extracellular levels of homovanillic acid, a metabolite of dopamine, in the caudate nucleus of freely moving rats. Local infusion of homovanillic acid close to the electrode confirmed that peak 3, at about 550 mV, could be used for this purpose. Thirty minutes of lever pressing for food reward was followed by an increase in homovanillic acid, maximal about 30 min later (+42%). An earlier and larger (+51%) increase in peak 2 (350-400 mV) was seen, highly correlated (r = 0.98) with the rate of lever pressing across individuals. A smaller decrease (-23%) in peak 1 (200 mV; ascorbic acid) was seen 75 min after the behavioural session. Administration of allopurinol, an inhibitor of uric acid production, selectively abolished peak 2. Allopurinol prior to lever pressing reduced the increase in peak 2 very substantially (by 77%), confirming that this too was mainly due to uric acid. These results indicate that linear sweep voltammetry can be used to study the time course of changes in dopamine metabolism, and in other neurochemicals, in individual freely moving rats in relation to behaviour under experimental control. More specifically, they demonstrate directly that rewarded lever pressing increases dopamine metabolism in the caudate, which had previously only been inferred from indirect approaches. The level of uric acid is also increased, and it is suggested that this may serve as an index of metabolic activity. PMID- 2586750 TI - Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. AB - The 2-deoxyglucose metabolic mapping technique has been used to investigate the neural mechanisms which underlie the symptoms of Parkinsonism in the 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease. In six cynomolgus monkeys, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was either (a) administered intravenously to induce generalized Parkinsonism, or (b) infused into one carotid artery to induce unilateral Parkinsonism. Post-mortem examination revealed profound cell loss from the substantia nigra, pars compacta either bilaterally or unilaterally in the two groups, respectively. In addition, there was pathological involvement of the ventral tegmental area and locus coeruleus in animals receiving intravenous 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. 2-Deoxyglucose autoradiography revealed widespread changes in 2-deoxyglucose uptake in the brains of parkinsonian animals when compared to controls. Most of these changes were in basal ganglia and related structures and were qualitatively similar in the two groups of experimental animals. Prominent increases in 2-deoxyglucose uptake were observed in the lateral segment of the globus pallidus (24-27%), the ventral anterior and ventral lateral nuclei of the thalamus (14-22%) and the nucleus tegmenti pedunculopontinus of the caudal midbrain (17-69%). A profound decrease (17-26%) in 2-deoxyglucose uptake was observed in the subthalamic nucleus. We propose these data to indicate that in 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism there is the following pattern of abnormal neuronal activity in basal ganglia circuitry: (i) increased activity in the projection from the putamen to the lateral segment of the globus pallidus; (ii) decreased activity in the projection from the putamen to the medial segment of the globus pallidus; (iii) decreased activity in the projection from the lateral segment of the globus pallidus to the subthalamic nucleus; (iv) increased activity in the projection from the subthalamic nucleus to the globus pallidus; and (v) increased activity in neurons of the medial segment of the globus pallidus projecting to the ventral anterior/ventral lateral thalamus and the pedunculopontine nucleus. These results are compared to the 2 deoxyglucose uptake findings in previous studies from this laboratory in hemiballism and hemichorea in the monkey. The central importance of the subthalamic nucleus in all three conditions is proposed, and supportive evidence for the excitatory nature of subthalamic efferent fibres is adduced. PMID- 2586751 TI - Modulation of synaptic transmission in the rabbit coeliac ganglia by gastric and duodenal mechanoreceptors. AB - The involvement of duodenal and gastric mechanoreceptors in the modulation of synaptic transmission was investigated in a rabbit sympathetic prevertebral ganglion. The present study was performed in vitro on the coeliac plexus connected to the stomach and the duodenum. The electrical activity of ganglionic neurons was recorded using intracellular recording techniques. The patterns of synaptic activation of these ganglionic neurons in response to the activation of mechanoreceptors by gastric or duodenal distension were investigated. Although gastric or duodenal distension was unable to elicit any fast synaptic activity in ganglionic neurons, it produced either an inhibition or a facilitation of the fast nicotinic excitatory postsynaptic potentials elicited by stimulation of the thoracic splanchnic nerves. In addition, this distension triggered long-lasting (3-11 min) modifications in the electrical properties of the ganglionic neurons, i.e. slow depolarizations (6-18 mV) or slow hyperpolarizations (3-6 mV), which were sometimes associated with a decrease in the input membrane resistance. After cooling of the nerves connecting the coeliac ganglia to the stomach, the activation of gastric or duodenal mechanoreceptors was no longer able to modify the fast synaptic activation or the electrical properties of the ganglionic neurons. The results demonstrate that gastric and duodenal mechanoreceptors project onto neurons of the coeliac ganglia and change their excitability as well as the central inputs they receive. The long duration of these modifications suggests that gastric and duodenal mechanoreceptors can modulate the activity of the neurons of the coeliac ganglia. PMID- 2586752 TI - Intraneuronal distribution of a synaptic vesicle membrane protein: antibody binding sites at axonal membrane compartments and trans-Golgi network and accumulation at nodes of Ranvier. AB - The distribution of a cholinergic synaptic vesicle-specific transmembrane glycoprotein (Buckley and Kelly, 1985, J. Cell Biol. 100, 1284-1294) was investigated in the entire electromotor neuron of Torpedo marmorata using a monoclonal antibody and immunocytochemistry at the light- and electron microscopical level (immunoperoxidase, colloidal gold). In the nerve, terminal binding of immunogold particles is restricted to synaptic vesicles. In the axon a number of additional membrane compartments like multivesicular bodies, vesiculotubular structures, lamellar bodies and electron-dense granules share the surface located synaptic vesicle-specific transmembrane glycoprotein-epitope. Membranous structures likely to represent the axoplasmic reticulum inside axons and nerve terminals are not labelled. Antibody-binding membrane compartments are accumulated at nodes of Ranvier. In the perikaryon the tubules of the trans-Golgi network as well as multivesicular bodies, lamellar bodies, electron-lucent vesicles, granules with electron-dense core and peroxisomes are labelled. Immunotransfer blots of isolated synaptic vesicles and tissue extracts of electric organ display a 100,000 mol. wt band of broad electrophoretic mobility typical of the synaptic vesicle-specific transmembrane glycoprotein. Extracts of electromotor nerve and electric lobe contain in addition a strong band at 85,000 mol. wt and a few lower molecular weight bands. We suggest that the synaptic vesicle originates directly from the trans-Golgi network. The endoplasmic reticulum is not involved in vesicle formation or retrieval. On retrograde transport the vesicle membrane compartment is likely to fuse with other intra axonal (endosomal?) organelles. PMID- 2586753 TI - Glutaminase-like immunoreactivity in the lower brainstem and cerebellum of the adult rat. AB - Distribution of putative glutamatergic neurons in the lower brainstem and cerebellum of the rat was examined immunocytochemically by using a monoclonal antibody against phosphate-activated glutaminase, which has been proposed to be a major synthetic enzyme of transmitter glutamate and so may serve as a marker for glutamatergic neurons in the central nervous system. Intensely-immunolabeled neuronal cell bodies were densely distributed in the main precerebellar nuclei sending mossy fibers to the cerebellum; in the pontine nuclei, pontine tegmental reticular nucleus of Bechterew, external cuneate nucleus, and lateral reticular nucleus of the medulla oblongata. Phosphate-activated glutaminase-immunoreactive granular deposits were densely seen in the brachium pontis and restiform body, suggesting the immunolabeling of mossy fibers of passage. In the cerebellum, neuropil within the granule cell layer of the cerebellar cortex displayed intense phosphate-activated glutaminase-immunoreactivity, and that within the deep cerebellar nuclei showed moderate immunoreactivity. These results indicate that many mossy fiber terminals originate from phosphate-activated glutaminase containing neurons and utilize phosphate-activated glutaminase for the synthesis of transmitter glutamate. Intensely-immunostained neuronal cell bodies were further observed in other regions which have been reported to contain neurons sending mossy fibers to the cerebellum; in the dorsal part of the principal sensory trigeminal nucleus, dorsomedial part of the oral subnucleus of the spinal trigeminal nucleus, interpolar subnucleus of the spinal trigeminal nucleus, paratrigeminal nucleus, supragenual nucleus, regions dorsal to the abducens nucleus and genu of the facial nerve, superior and medial vestibular nuclei, cell groups f, x and y, hypoglossal prepositus nucleus, intercalated nucleus, nucleus of Roller, reticular regions intercalated between the motor trigeminal and principal sensory trigeminal nuclei, linear nucleus, and gigantocellular and paramedian reticular formation. Neuronal cell bodies with intense phosphate activated glutaminase-immunoreactivity were also found in other brainstem regions, such as the paracochlear glial substance, posterior ventral cochlear nucleus, and cell group e. Although it is still controversial whether all glutamatergic neurons use phosphate-activated glutaminase in a transmitter related process and whether phosphate-activated glutaminase is involved in other metabolism-related processes, the neurons showing intense phosphate-activated glutaminase-immunoreactivity in the present study were suggested to be putative glutamatergic neurons. PMID- 2586754 TI - Transient direct connection of vestibular mossy fibers to the vestibulocerebellar Purkinje cells in early postnatal development of kittens. AB - Postnatal development of mossy fiber afferents from the vestibular and the visual system to the vestibulocerebellum was studied electrophysiologically and morphologically. In kittens anesthetized with pentobarbital sodium and N2O plus halothane, extracellular simple and complex spikes of Purkinje cells were recorded in the flocculus, nodulus and uvula. In the flocculus, stimulation of the VIIIth, but not the optic nerve, evoked simple spike responses with a latency of 16 ms at the day of birth which decreased to 5 ms by day 15 (short latency group). On the other hand, another group of simple spike responses with much longer latencies (50-80 ms) began to be elicited on day 7 via both the optic and VIIIth nerves. The latency decreased to 24 ms by day 15 and 10 ms on day 30. These latencies further shortened with development to the adult latency value (3 5 ms). Simple spike responses of the short latency group were also evoked in the nodulus and uvula from the VIIIth nerve with a slightly longer latency than that in the flocculus (23 ms on day 3 and 12 ms on day 17). Because of the immaturity of granule cells in early postnatal days, short latency simple spike responses from the VIIIth nerve suggested the direct synaptic connection of vestibular mossy fibers with Purkinje cells. Horseradish peroxidase was injected into the white matter of the flocculus, nodulus and uvula in slice preparations. Mossy fibers labeled with horseradish peroxidase showed fine branches extending to reach Purkinje cell somata from mossy swellings in the internal granular layer during days 2-20. Electron microscopy showed that the labeled mossy fibers made intimate contacts with Purkinje cell somata and the terminals contained many round synaptic vesicles. Pre and postsynaptic densities were occasionally found. After day 20, direct mossy fiber connections with Purkinje cells could not be observed. During days 7-20, these direct connections, as well as mossy fiber granule cell connections could be observed. It was demonstrated that during early postnatal development, vestibular mossy fibers temporarily make direct contact with Purkinje cells, through which impulses could be transmitted to elicit simple spikes in Purkinje cells. PMID- 2586755 TI - Acetylcholine receptor expression in primary cultures of embryonic chick myotubes -I. Discoordinate regulation of alpha-, gamma- and delta-subunit gene expression by calcitonin gene-related peptide and by muscle electrical activity. AB - The neuropeptide calcitonin gene-related peptide calcitonin gene-related peptide, and muscle electrical activity regulate in opposite directions the content of nicotinic acetylcholine receptor alpha-subunit mRNA in primary cultures of chick embryonic myotubes. Indeed, treating the cells with calcitonin gene-related peptide or blocking the spontaneous activity of muscle cells by tetrodotoxin (an inhibitor of sodium channels) increases, although to different levels, the content of acetylcholine receptor alpha-subunit mRNA [Fontaine B., Klarsfeld A. and Changeux J. P. (1987) J. Cell Biol. 105, 1337-1342; Klarsfeld A. and Changeux J. P. (1985) Proc. natn. Acad. Sci. U.S.A. 82, 4558-4562]. In this paper, we demonstrate that, under these in vitro culture conditions, calcitonin gene related peptide (0.1 microM) and tetrodotoxin (0.5 microM) regulate to a smaller extent (no more than 2.5-fold above control) the levels of acetylcholine receptor gamma- and delta-subunit mRNAs. No effect of either compound on acetylcholine receptor biosynthesis was observed during the initial three days of culture. The response to calcitonin gene-related peptide was already maximal when the cells were treated between days three and four after plating (about 3-fold increase of the alpha-subunit mRNA level). The effect of tetrodotoxin resulted in a six-fold increase of the acetylcholine receptor alpha-subunit mRNA level in cells treated between days three and four, and still increased when the cells were exposed to tetrodotoxin through days six and eight (up to a maximum of 20-fold).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2586756 TI - Acetylcholine receptor expression in primary cultures of embryonic chick myotubes -II. Comparison between the effects of spinal cord cells and calcitonin gene related peptide. AB - Spinal cord cells co-cultured with primary chick myotubes caused a 1.5-3-fold increase in the number of muscle surface acetylcholine receptors assayed with [125I]alpha-bungarotoxin. This increase did not result from the metabolic stabilization of the acetylcholine receptor protein and was at least partially due to a stimulation of acetylcholine receptor biosynthesis up to the level of the accumulation of alpha-subunit mature and partially spliced precursor mRNAs. A medium conditioned by spinal cord cells also caused a rise in acetylcholine receptor number. This increase did not coincide with an augmentation of the intracellular cyclic AMP level as reported for the neuropeptide calcitonin gene related peptide. In contrast, spinal cord cells and the medium conditioned by them potentiated the effect of calcitonin gene-related peptide on acetylcholine receptor number. Stimulation of acetylcholine receptor synthesis by the conditioned medium was blocked by the protein kinase C activator 12-O tetradecanoyl phorbol-13-acetate and by the calcium ionophore A23187. These two compounds have already been reported to block the increase of acetylcholine receptor number produced by the voltage sensitive sodium channel antagonist tetrodotoxin which stimulates acetylcholine receptor biosynthesis by blocking spontaneous electrical activity of the cultured muscle cells. The possibility that different neural factors and second messenger systems are involved in the regulation of acetylcholine receptor biosynthesis during the development of the neuromuscular junction is discussed. PMID- 2586757 TI - A developmentally regulated axonal glycoprotein (7-8D2 antigen) with a restricted distribution in mature rat brain. AB - 7-8D2 is a mouse monoclonal IgGl antibody which recognizes a neuronal cell surface antigen in rat brain. Immunohistochemical techniques reveal the antigen to be present most abundantly in the cerebellum of the adult brain, where it is expressed by the cell bodies and fibres of the granule neurons. Lower levels of staining were found in the neuropil of the hippocampus, in some fibres of the corpus callosum and in the most superficial layer of the cerebral cortex. Immunoelectron microscopy confirmed that the antigen was present on the surface of the parallel fibres in the cerebellum and showed that it was absent from glial, Purkinje or stellate cell membranes. The antigen had a more widespread distribution early in development, and the restricted adult distribution was achieved by the end of the second postnatal week. Immunoblotting of samples of adult rat brain shows that the antigen appears as a close doublet of bands at 211,000 mol. wt. This result was confirmed by immunoprecipitating the antigen from metabolically labelled glycoproteins prepared from cultured cerebellar interneurons. Immunoblotting and immunohistochemical experiments were in agreement that the cerebellum contained high levels of the antigen, and that lower but significant amounts could be found in other brain regions, notably the hippocampus and the cerebral cortex. The localization data and the changes in the distribution of the antigen may suggest some role for this molecule during early brain development. PMID- 2586758 TI - Dendrites of hypothalamic magnocellular neurons release neurohypophysial peptides by exocytosis. AB - Exocytosis of neurosecretory granules from dendrites of magnocellular neurons can be visualized electron microscopically after incubation of hypothalamic brain slices in media containing 1.2 mM tannic acid, which stabilizes extracellular peptidergic granule cores, and permits their immunocytochemical identification. Morphometric analysis of stimulated slices demonstrates that exocytosis of neurosecretory granules from the dendrites of magnocellular neurons can account for the vasopressin and oxytocin known to be released into the hypothalamus. Exocytosis from cell bodies of magnocellular neurons was not observed in stimulated slices from normal rats but, when granules had been caused to accumulate in the neuronal somata by prior administration of colchicine, exocytosis of granules from the somata was unambiguously identified. These data demonstrate exocytosis from dendrites and cell bodies of a mammalian peptidergic neuron, and show that all parts of their plasmalemma are competent for exocytosis of granules. PMID- 2586759 TI - The cholinergic innervation of normal and transplanted superior colliculus in the rat: an immunohistochemical study. AB - The distribution of choline acetyltransferase was determined in normal and transplanted rat superior colliculus with choline acetyltransferase immunohistochemistry. This distribution was compared to the pattern of histochemically detected acetylcholinesterase activity. To determine cholinergic input to the superficial superior colliculus, double labelling experiments combining retrograde tracing methods and choline acetyltransferase immunohistochemistry were carried out. No choline acetyltransferase-containing neurons were observed in the rat superior colliculus. A dense network of choline acetyltransferase-immunoreactive fibres and terminals was seen in the intermediate layers of the normal superior colliculus. The distribution was patchy and very similar to the pattern of acetylcholinesterase activity. Occasional fibres and terminals were seen in the deep tectal laminae. The superficial layers contained a low number of choline acetyltransferase-stained fibres and terminals but a comparatively high level of acetylcholinesterase activity. Following a unilateral injection of a tracer into the superficial superior colliculus, retrogradely labelled choline acetyltransferase immunoreactive neurons were found in the dorsal and ventral subnuclei of the ipsilateral parabigeminal nucleus. As in the normal superior colliculus, choline acetyltransferase-positive neurons were not found in tectal transplants. However, choline acetyltransferase-immunoreactive fibres and terminals were seen in grafts but only in those which had extensive connections with the host midbrain. The pattern of staining most closely resembled that seen in the intermediate layers of the normal superior colliculus. The similar arrangement of choline acetyltransferase and acetylcholinesterase activity in the intermediate layers of normal rat superior colliculus provides further evidence for cholinergic innervation to these layers, probably originating in the dorsal and pedunculopontine tegmental nuclei. The data from the double labelling experiments indicate that the choline acetyltransferase-immunoreactive terminals observed in the superficial layers represent the terminal field of an ipsilateral cholinergic projection from the parabigeminal nucleus. Tectal grafts receive cholinergic innervation from the host. The evidence suggests that much of this input derives from the cholinergic nuclei in the brainstem tegmentum which normally project to the intermediate tectal layers. PMID- 2586760 TI - Phenylethanolamine N-methyltransferase-immunoreactive terminals synapse on adrenal preganglionic neurons in the rat spinal cord. AB - Adrenergic neurons in the C1 region in the ventrolateral medulla oblongata send descending axons into spinal cord which terminate in thoracic and upper lumbar segments, overlapping the distribution of sympathetic preganglionic neurons. The present study was undertaken to determine whether adrenergic fibers synapse directly on preganglionic neurons which innervate the adrenal medulla and to examine the ultrastructure of these fibers during development. The ultrastructure and synaptology of adrenergic axons in the intermediolateral nucleus of mid thoracic spinal cord were studied in 7-, 9-, 24-, 30-, 60-, and 90-day-old rats using immunocytochemical staining for phenylethanolamine N-methyltransferase, the epinephrine-synthesizing enzyme. Phenylethanolamine N-methyltransferase immunoreactivity was observed in the cytoplasm of unmyelinated axonal varicosities and intervaricose segments in the neuropil of intermediolateral nucleus. Phenylethanolamine N-methyltransferase-immunoreactive synaptic boutons were filled with spherical electron-lucent vesicles and occasional larger dense core vesicles. These boutons were observed to form symmetrical synaptic contacts with dendritic processes at all ages examined. Asymmetrical synapses on dendrites were also observed in adult rats. Axosomatic synaptic contacts were frequently observed in immature rats, but were never observed in adult rats. To determine whether adrenergic axons synapse on preganglionic neurons which project to the adrenal medulla, adrenal preganglionic neurons were retrogradely labeled with horseradish peroxidase and adrenergic axons were stained for phenylethanolamine N methyltransferase-immunoreactivity. In young rats, phenylethanolamine N methyltransferase-immunoreactive boutons were observed to form symmetrical axosomatic and axodendritic synaptic contacts with adrenal preganglionic neurons in intermediolateral nucleus. These contacts had already formed by postnatal day 7, the youngest age studied. In contrast, it was not possible to verify that adrenal preganglionic neurons receive adrenergic innervation in adult rats, since phenylethanolamine N-methyltransferase-immunoreactive boutons were only observed in contact with small diameter dendrites that were not retrogradely labeled by horseradish peroxidase. These studies demonstrate that adrenal preganglionic neurons receive adrenergic synapses prior to the first postnatal week. The initial synapses which form on preganglionic somata and proximal dendrites appear to reorganize late in development. It is suggested that these become more distally located as the dendritic tree matures. More generally, these observations suggest that adrenergic bulbospinal neurons are involved in central regulation of adrenal development and function. PMID- 2586761 TI - New strategies in dopaminergic therapy of Parkinson's disease: the use of a controlled-release formulation. London, England, April 28 and 29, 1989. Proceedings. PMID- 2586762 TI - A pharmacokinetic and pharmacodynamic comparison of Sinemet CR (50/200) and standard Sinemet (25/100). AB - Seventeen patients with advanced Parkinson's disease who had fluctuations in motor performance while taking standard Sinemet (STD) 25/100 underwent daylong pharmacokinetic and clinical observation studies while taking both STD and Sinemet CR, a new controlled-release formulation containing 50 mg carbidopa and 200 mg levodopa. During treatment with Sinemet CR, there was an increase in the interdose interval, a reduction in the number of medication doses taken each day, an increase in total "on" time, and a reduction in the number of "off" episodes. Total daily levodopa intake was greater with Sinemet CR, although the bioavailability of levodopa and carbidopa from the two preparations was equivalent. The variability in plasma levodopa levels was significantly less with Sinemet CR. The slower release of drug from Sinemet CR was reflected in a prolongation of the Tmax for levodopa and a prolongation of the interval from Tmax to the succeeding trough levodopa level. Clinically, peak antiparkinsonian effect occurred later and lasted longer with the CR preparation. PMID- 2586763 TI - Experience with continuous enteral levodopa infusions in the treatment of 9 patients with advanced Parkinson's disease. AB - Nine patients with advanced Parkinson's disease were started on continuous enteral levodopa infusions during the past 3 years. Six have remained on the infusion system for 1 to 28 months. All patients experienced immediate amelioration of motor fluctuations, and 5 patients continue to obtain relief. One patient found that his ability to achieve the "on" state without unacceptable dyskinesia waned. Experience thus far indicates that continuous long-term levodopa infusions are a practical but complex form of therapy for patients failing more conventional treatment. PMID- 2586764 TI - Development and progression of motor fluctuations and side effects in Parkinson's disease: comparison of Sinemet CR versus carbidopa/levodopa. AB - We compared the chronic (2-year) effect of substitution with Sinemet CR with the effect of continued administration of standard Sinemet on motor fluctuations and drug-induced side effects in Parkinson's disease (PD). Twelve patients in each treatment group were pair-matched for age, PD duration, duration of levodopa therapy, dosage of Sinemet, PD disability, and side-effect prevalence at study entry. After 2 years, both groups were more disabled from their PD than at baseline; the disability scores were equivalent for the 2 treatments. The Sinemet CR group had fewer fluctuations and fewer side effects. Compared with the standard Sinemet group, Sinemet CR patients had more "on" time (mean 83% versus 62%, p less than 0.001), and had a lower prevalence of disabling chorea (p less than 0.007), dystonia (p less than 0.003) and sleep disruption (p less than 0.002). Prevalence of hallucinations was equivalent for the 2 groups. These results suggest that Sinemet CR is beneficial in ameliorating and preventing the high frequency of some side effects of standard Sinemet treatment. PMID- 2586765 TI - Effect of controlled-release carbidopa/levodopa on motor performance in advanced Parkinson's disease. AB - Twenty parkinsonian patients were treated with controlled-release carbidopa/levodopa (Sinemet CR). All were affected by therapeutic response fluctuations related to the timing of drug administration. The daily dosage after 1 year, 766 mg +/- 250 mg, was increased by 23% compared with standard Sinemet dosage, without additional secondary effects. Parkinsonian scores improved by 43%; the prolongation of "on" periods was 63%. Nevertheless, 7 patients withdrew from this study during the 1st month of treatment. Only 1 withdrew due to an adverse reaction to the formulation, a recurrence of hallucinations. The progressive effect of the 1st morning dose and the often unpredictable time at which the product first takes effect were found to be frustrating for the other patients who withdrew. We believe that this disappointment can be avoided by giving new patients the controlled-release formulation from the start of therapy. PMID- 2586766 TI - Treatment of early Parkinson's disease with controlled-release levodopa preparations. AB - Therapeutic responses to Sinemet CR were studied in 37 patients with early Parkinson's disease previously treated with standard (Madopar) or controlled release (Madopar HBS) levodopa/benserazide combinations. Patients were followed up for a 3-month period. The optimal therapeutic response of parkinsonian disability to Sinemet CR was equal to that obtained with Madopar or Madopar HBS. The optimal therapeutic dosage of Sinemet CR was equal to that of Madopar HBS but 12% higher than that of standard Madopar. However, with Sinemet CR treatment, the number of daily doses needed was significantly fewer than with both previous treatments. End-of-dose failure, which had developed in 4 patients, and peak-dose dyskinesias present in 6 patients during treatment with standard Madopar, improved significantly with Sinemet CR. Thus, Sinemet CR seems to be beneficial and useful in the treatment of early Parkinson's disease. PMID- 2586767 TI - Sinemet CR in the treatment of patients with Parkinson's disease already on long term treatment with levodopa. AB - The efficacy of controlled-release Sinemet was evaluated in a 52-week open trial involving 20 patients (14 men, 6 women; mean age 66 years, range 56 to 82) with idiopathic Parkinson's disease of 8 years' mean duration. The mean daily dosage of levodopa was 662.5 mg (200 to 1600 mg) on entering the study and 800 mg (200 to 2400 mg) after 52 weeks. The mean number of daily doses was reduced from 5.0 (2 to 16) at entry to 3.3 (1 to 6) after 52 weeks. Rigidity, tremor, and bradykinesia were scored at 3 intervals during baseline and 8 intervals during the study on controlled-release levodopa. All parameters improved, with maximum improvement seen at week 12. Side effects were less frequent on the controlled release preparation. After 5 months, 1 patient developed protracted dyskinesia with freezing episodes and end-of-dose deterioration on dose frequency reduction. PMID- 2586768 TI - Experiences with Sinemet CR in the Paracelsus-Elena-Klinik. AB - In an open-label study, 20 patients with peak-dose dyskinesia and/or end-of-dose fluctuations were switched from standard Sinemet to Sinemet CR. Seventeen patients showed good tolerance and therapeutic results for at least 6 months. However, 10 patients showed a slight decrease of this improvement after 6 months; 3 had to be put back on standard Sinemet because of hallucinations (1) or accentuation of dyskinesia and akinesia (2). For optimal results, a higher dosage is needed (mean = 33%), but the number of doses per day can be reduced (mean = 30%). PMID- 2586769 TI - Long-term clinical efficacy of Sinemet CR in patients with Parkinson's disease. AB - Sinemet CR, a controlled-release form of carbidopa/levodopa, was administered for 36 or 39 months to 8 patients with Parkinson's disease in an open-label study. On standard Sinemet each patient had experienced "wearing off" phenomena, and 5 had also experienced random "off" episodes. Daily "on" time, dyskinesia time, disability score, levodopa dosage requirement, and dosing frequency on Sinemet CR were compared with baseline values on standard Sinemet therapy. After both 3 and 36 or 39 months of Sinemet CR therapy, 5 patients showed increased daily "on" time compared with baseline. All 8 required fewer daily doses after 3 months on Sinemet CR, but only 3 were still taking fewer doses after 36 or 39 months. Disability scores remained essentially unchanged. Patients continued to elect to remain on Sinemet CR over the 3-year period, citing improved predictability of response and less severe and precipitous "off" episodes as the main reasons. This experience suggests that patient acceptance of Sinemet CR remains high. A modest improvement in "on" time can be achieved and maintained in some patients for as long as 3 years. However, as with standard Sinemet, dosing frequency for Sinemet CR may need to be gradually increased with time in order to maintain benefits achieved. PMID- 2586770 TI - Chronic progressive myelopathy associated with HTLV-I: oligoclonal IgG and anti HTLV-I IgG antibodies in cerebrospinal fluid and serum. AB - Among 22 patients with human T-lymphotropic virus type I (HTLV-I)-associated chronic progressive myelopathy, agarose isoelectric focusing (AIF) revealed oligoclonal IgG bands in 21: in 3 in CSF only; in 11 in CSF and to some extent in serum; and in 7, identical patterns in CSF and serum. By immunoblot after AIF of CSF and serum, we observed bands of anti-HTLV-I IgG antibodies in 19 patients: in 5 in CSF only; in 9 in CSF and partly in serum; and in 5, identical in CSF and serum. Oligoclonal anti-HTLV-I IgG antibody bands could only partly be traced to oligoclonal IgG bands. If, prior to AIF, serum and CSF were absorbed with HTLV-I antigen, practically all oligoclonal HTLV-I-specific IgG antibody activity was abolished, while the oligoclonal pattern of total IgG was affected only to a minor extent. Alongside with HTLV-I-specific oligoclonal B cell response, HTLV-I myelopathy is regularly accompanied by production of oligoclonal IgG of unknown antibody specificities. PMID- 2586771 TI - HTLV-I-associated myelopathy and polymyositis in a US native. AB - A patient who had always lived in the United States had an HTLV-I infection and a chronic myelopathy clinically mimicking amyotrophic lateral sclerosis. Needle EMG and nerve conduction studies were consistent with anterior horn cell disease but muscle biopsy showed denervation and an inflammatory myopathy. Serum HTLV-I antibody tests were positive and HTLV-I DNA was present in peripheral leukocytes. This is the 1st reported US native with HTLV-I-associated myelopathy and polymyositis. PMID- 2586772 TI - Head trauma with loss of consciousness as a risk factor for Alzheimer's disease. AB - We identified all incident cases of clinically diagnosed Alzheimer's disease among the population of Rochester, MN, with onset from 1965 through 1974. A control (selected from the same community) was matched to each case by age, race, sex, and length of stay in Rochester. We studied 274 case-control pairs. Using the records linkage system available for residents of this community, we abstracted information on the occurrence of head trauma with loss of consciousness (LOC) from the medical records of both cases and controls. There were 5 pairs in which the case suffered an episode of head trauma with LOC but the control did not, and 4 pairs in which the control suffered an episode of head trauma with LOC but the case did not. We failed to detect a statistically significant difference between the 2 groups. This study overcomes many problems encountered in previous case-control studies reporting this association. The sample size was large; severity of head injury was documented in high-quality medical records; data about head injury were recorded before the onset of dementia: equal quality of data were available for cases and controls; and, since the study was population-based, there was no selection bias for cases or controls. PMID- 2586773 TI - Ibuprofen-induced meningitis: detection of intrathecal IgG synthesis and immune complexes. AB - We report a case of ibuprofen-induced meningitis in an otherwise healthy individual. This is the 1st case documenting intrathecal IgG synthesis and immune complex formation in this disorder. The immunopathogenesis remains obscure, but is suggestive of an antigen-specific process requiring the presence of or exposure to ibuprofen. PMID- 2586774 TI - Acute and chronic effects of propranolol and primidone in essential tremor. AB - We studied the acute and chronic effects of propranolol and primidone in essential tremor by administering long-acting propranolol (80 to 160 mg/d) and primidone (50 to 250 mg/d) to 50 patients. We evaluated patients at 1, 3, 6, 9, and 12 months after treatment and assessed tremor by subjective rating by patients, clinical scoring, and thermographic (accelerometer) recordings. Acute adverse reactions occurred in 8% with propranolol and 32% with primidone. Propranolol was without therapeutic effect in 30%, and 32% had no benefit from primidone. Significant chronic side effects occurred in 17% taking propranolol and in 0% with primidone. Tolerance to drug effect occurred with chronic treatment in 12.5% of patients with propranolol and 13.0% with primidone. We conclude that propranolol and primidone are effective long-term treatment for some patients with essential tremor. Acute adverse reactions with primidone and side effects with chronic use of propranolol hamper therapy. PMID- 2586775 TI - History of dementia and Parkinson's disease in 1st-degree relatives of patients with Alzheimer's disease. AB - We assessed the family history of dementia and Parkinson's disease in 198 Dutch patients with Alzheimer's disease diagnosed before the age of 70 years, and in 198 age- and sex-matched healthy population controls. Of the Alzheimer patients, 48% had at least 1 1st-degree relative with dementia, compared with 19% of the controls. There were 24 patients and 1 control with 2 or more 1st-degree relatives with dementia, yielding a relative risk of 40.0. More Alzheimer patients than controls had a 1st-degree relative with Parkinson's disease, with a relative risk of 2.9. This study strongly confirms earlier findings of familial aggregation of Alzheimer's disease and provides evidence for familial aggregation of Alzheimer's disease with Parkinson's disease. The latter may point at a joint etiology of these diseases. PMID- 2586776 TI - Symptomatic congenital hydrocephalus in the elderly simulating normal pressure hydrocephalus. AB - In a series of 30 older patients shunted for symptomatic hydrocephalus, we found 3 with a head circumference at or greater than the 98th percentile. In 2, we demonstrated deterioration over 6 and 12 months by serial videotaping of gait and neuropsychological testing. In the 3rd, serial lumbar punctures over a 6-month period gave temporary improvement. In each, CTs showed ventriculomegaly without transependymal flow. One patient had an Arnold-Chiari type I abnormality identified by MRI. All had systemic hypertension. CSF pressure monitoring showed CSF pressure greater than 15 mm Hg 39% of the time in 1 patient, and 100% in another. All improved with ventriculoperitoneal shunting. Patients with probable compensated congenital hydrocephalus who functioned well throughout most of their lives may become symptomatic as they age but improve with shunt surgery. The head circumference should be measured in all older hydrocephalic patients. PMID- 2586777 TI - Variables predicting surgical outcome in symptomatic hydrocephalus in the elderly. AB - We prospectively studied 30 older patients who had shunt surgery for symptomatic hydrocephalus and measured outcome using serial videotaping of gait, neuropsychological testing, and the Katz index of activities of daily living. Twenty-three patients improved and 7 did not. Using univariate analysis and the Fisher exact test, we found that the following variables were significantly related to outcome: (1) time B-waves present on 24-hour CSF pressure record; (2) anterior/posterior ratio on slice 4 of regional cerebral blood flow study; (3) duration of dementia prior to surgery; and (4) gait abnormality preceding dementia. The following variables showed a trend towards significance: (1) time CSF pressure greater than 15 mm Hg; and (2) scoring either pass or fail on the Multilingual Visual Naming Test. We conclude that several variables are significantly associated with surgical outcome in symptomatic hydrocephalus in the elderly and can be used in deciding whether to recommend surgery. PMID- 2586778 TI - Reaction times of movement preparation in patients with Parkinson's disease. AB - We studied the onset of preparatory postural responses and subsequent voluntary movements by measuring soleus muscle activities in the standing position in 20 patients with Parkinson's disease. We measured the postural response in preparing to rise on tiptoe as the onset of the premotion silent period (PMSP). Our patients showed no delay when compared with age-matched healthy controls, but did show a significant delay in the onset of voluntary movement. The elongated PMSP (increased duration of the preparatory postural adjustments) was related to the severity of bradykinesia. Results indicate that the conventional reaction time is increased in patients with Parkinson's disease, even though there is no delay of central processing for the preparation of voluntary movements, and that there is bradykinesia of involuntary postural movements. PMID- 2586779 TI - MRI detects cerebral involvement in neurologically asymptomatic patients with adrenoleukodystrophy. AB - X-Linked adrenoleukodystrophy (ALD) is a peroxisomal disorder which affects the white matter of the CNS. MRI detected white matter lesions in 2 of 7 patients with biochemically proven ALD but without neurologic manifestations. PMID- 2586780 TI - Use of antithrombotic drugs in the treatment of acute ischemic stroke: a survey of neurologists in practice in the United States. AB - In an attempt to determine the opinions and practices of neurologists regarding the use of antithrombotic drugs in the treatment of acute ischemic stroke, we conducted a survey of 349 randomly selected neurologists from throughout the United States. Responses were received from 247 (71%), and 219 identified themselves as primary or consulting physicians for patients with acute ischemic stroke. During the previous 12 months, these 219 physicians estimated that they had seen a total of 14,636 patients within 24 hours of acute ischemic stroke, and 22% of these patients were treated with heparin. The most frequently reported indications were prevention of recurrent cerebral embolism (82% of physicians) and progressing stroke (70%). Despite the frequent use of heparin, only 6.4% of neurologists felt that it has been shown to be effective, and 16.4% felt that it has been shown to be of no value. The primary concern about the use of heparin was lack of proven efficacy in 48% and safety concerns in 41%. Results of a future trial testing the efficacy of antithrombotic drugs would be useful for most neurologists in their management of patients with acute or progressing ischemic stroke. PMID- 2586781 TI - Pattern and concentration of IgG in cerebrospinal fluid in neurosarcoidosis. AB - Reports have suggested that the pattern of CSF IgG differentiates neurosarcoidosis from multiple sclerosis. We examined CSF and serum of 7 patients with neurosarcoidosis to determine concentrations of IgG and albumin and the presence of oligoclonal bands. Our results showed that neurosarcoidosis may have associated abnormalities of IgG synthesis and oligoclonal bands present in CSF, but without a consistent pattern. PMID- 2586782 TI - Cerebral infarction following herpes zoster: the enlarging clinical spectrum. PMID- 2586783 TI - Bilateral ballism in multiple sclerosis. PMID- 2586784 TI - Post-traumatic torticollis. PMID- 2586785 TI - Phenytoin suspension. PMID- 2586787 TI - Isolated CNS angiitis. PMID- 2586786 TI - Diagnosis of 1st seizure. PMID- 2586789 TI - Experimental global cerebral ischemia in rats. II. Ultrastructural changes in the Ca1 sector of the hippocampus in the post-ischemic period. PMID- 2586788 TI - Modelling of saccades. PMID- 2586790 TI - Pattern of vegetative innervation of the pia mater vessels in phylogeny. PMID- 2586791 TI - Conditions of blood flow in capillaries of cerebral cortex in control and ischemia. PMID- 2586792 TI - Dynamics of changes in astrocytes and neurons of rabbit cerebral cortex induced by temporary blood supply deficiency. PMID- 2586793 TI - Heterogeneous arterial responses in postischemic state of cerebral cortex. PMID- 2586794 TI - Ultrastructure of neurons from the CA1 sector of Ammon's horn in short-term cerebral ischemia in Mongolian gerbils. PMID- 2586795 TI - Ultrastructure of capillaries and neuroglial cells in the hippocamus (sector CA1) during short-lasting ischemia and following blood recirculation. PMID- 2586797 TI - Studies of dry weight of cortical neurons under conditions of osmotic brain edema development in rabbits. PMID- 2586796 TI - Does pH reduction contribute to postischemic brain edema development? PMID- 2586798 TI - Pathophysiological characteristics of clinical death in rats. PMID- 2586799 TI - Experimental global cerebral ischemia in rats. I. Ultrastructural changes in cerebral cortex in the postischemic period. PMID- 2586800 TI - [Comparative scintigraphic functional study of 3 different reconstruction technics following total gastrectomy]. AB - Esophago-jejunal reconstruction, after total gastrectomy, is best performed by one of the following three operations: interposed jejunal loop, Roux-en-Y loop and "omega" loop with Braun anastomosis. To assess the effects of the three mentioned techniques three groups of 15 patients each were examined after total gastrectomy for I, II or III stage cancer. Four to ten months after surgery all patients underwent the following tests: a) esophago-jejunal transit with labeled solid meal; b) cholangio-scintigraphy and c) absorption test of biliary acids. A group of 10 patients, without gastrointestinal pathology, was selected for comparison. The data obtained from the comparative study, in agreement with the opinions held by many Authors and our previous research, demonstrate that the interposition of jejunal loop (Mouchet) is the reconstructive technique closest to the unoperated stomach and, for this reason, is to be preferred after total gastrectomy. PMID- 2586801 TI - [Conservative treatment of simple, uncomplicated diverticulitis. Preliminary study for evaluating the effectiveness of a method of topical therapy: rectal perfusion]. AB - Transit times and distribution modalities of an oily mixture used as a vehicle for drugs administered by rectal perfusion in topical therapy in patients with uncomplicated diverticulitis of the colon have been examined. X-ray study makes it possible to state that the technique is mainly indicated in descending colon and sigmoid localisations, segments in which the oily mixture distributes homogeneously and massively in all patients treated. PMID- 2586802 TI - [Possibility of radiology in the study of defection disorders]. AB - Chronic constipation and defecation disorders are a very common disease, but the diagnosis is often unsatisfactory and therefore therapy is mostly inadequate. The purpose of this paper is to demonstrate the contribution of radiological procedures and mainly of the defecography, in improving and determining the diagnosis itself. Many normal and pathological cases are reviewed, described and demonstrated by radiological patterns. Finally, a correct protocol of different procedures, radiological and not, for morphological and functional study of large bowel and pelvis floor is stressed. PMID- 2586803 TI - [Evaluation of regional perfusion as an indicator of resectability in patients with centrally located bronchogenic carcinoma]. AB - The value of using regional ventilation (V) and perfusion (Q) tests as signs of resectability has been analysed in 17 patients with centrally located lung cancers who underwent thoracotomy. The criteria for inclusion into the study were the following: (1) histological diagnosis of non-oat-cell carcinoma, (2) no distant metastases, (3) Q in the affected lung less than 40% and (4) evaluation by computed tomography of the extent of the tumor. Regional perfusion was investigated by intravenously injected 133 Xenon. CT scan proved to be the most sensitive test (90%) in order to identify non-resectable lesions; in 2 cases, however, the tumor was erroneously judged non-operable (specificity = 71%). For the evaluation of V and Q data, two parameters were assumed as a non resectability index: (1) Q less than or equal to 30% and (2) V/Q greater than or equal to 1.5. Sensitivity was 80% for the former and 70% for the latter parameter, while specificity was 85% and 100% respectively. In conclusion, V and Q study may provide highly specific informations on the resectability of centrally located lung cancers, especially when assuming V/Q greater than or equal to 1.5 as discriminating value. PMID- 2586804 TI - [Applied effectiveness of human fibrin glue (Tissucol) in tracheal reconstruction. Experimental research with a clinical orientation]. AB - Tracheal surgery is not without complications in the genesis of which a by no means secondary part is played by the suture material use. To obviate these complications a variety of resorbable materials have been studied. In a personal experimental study in the rabbit, the usefulness of a human fibrin glue was assessed in terms of two of its properties: its adhesive capacity and its ability to seal the anastomosis. In the first place, use of the glue made it possible to reduce the number of suture points employed in fashioning the anastomosis. This is an important result considering the role played by the suture material in favouring the appearance of granulations and restenosis. Second, Tissucol has a good sealant effect on the anastomosis and reduces postsurgical complications such as subcutaneous emphysema and perianastomotic abscess. Finally, it should be observed that this material also offers good control of intraoperative haemorrhage. PMID- 2586805 TI - [Treatment of gynecomastia using a trans-areolar incision]. AB - Thirty cases of gynecomastia treated surgically in Rio de Janeiro are presented. Possible aetiological factor are discussed and the technique employed, trans areolar incision and preparation of two retro-areolar flaps, described. The technique may be associated or not with liposuction. PMID- 2586807 TI - Post-appendectomy wound infection, a solved problem? AB - Over a 3.5 year period, 550 patients underwent an emergency operation under the diagnosis of acute appendicitis. The appendix proved to be normal in 82 patients, the other 468 patients had signs of acute inflammation with perforation in 142 cases. Management followed a strict protocol with single dose metronidazole as preoperative antibiotic prophylaxis and liberal open wound treatment in case of gross contamination. Consequently, the subcutaneous tissues and the skin were left open in 218 patients. The overall wound infection rate (1.3%) and the intra abdominal abscess rate (1.1%) were extremely low. Open wound treatment was well accepted by the patients, did not prolong the hospital stay and gave good cosmetic results. PMID- 2586806 TI - [Conservative intervention in tumors of the papilla of Vater. Apropos of 2 new cases]. AB - On the basis of two new cases of cancer of the papilla of Vater, stress is laid on the indication for and value of duodeno-cephalopancreatectomy as the sole radical intervention. Conservative papillectomy should be confined to special cases (advanced age, general condition poor) with good long-term results. PMID- 2586808 TI - Failure of quantitative venous photoplethysmography to assess venous insufficiency: a prospective clinical study. AB - The increase of deep venous reconstructive surgery necessitates reliable tests for evaluation of the results, which requires quantization of the expelled volume. This could only be done with invasive measurements, but now it seems possible to calibrate photoelectric cells, and quantize the results. Nineteen limbs of patients with deep venous disease and seven limbs of healthy volunteers were evaluated, with methods known from the literature. In addition to measurements in standing position, these methods were used in the more patient friendly sitting position. Invasively and noninvasively measured recovery times correlated well in the standing (R = 0.83) and in the sitting position (R = 0.86). However, the quantization of expelled volume did not significantly correlate. Also, the differences between expelled volume of controls and patients were only significant with invasive measurements in the standing position (P = 0.006) as well as in the sitting position (P = 0.004). The differences were not significant with the noninvasive method. In our opinion, photoelectric cells still do not offer an alternative for invasive measurements in the evaluation of results after venous reconstructive surgery. PMID- 2586809 TI - The Lynch syndrome; a high-risk factor for colorectal carcinoma. AB - Based on the case history of two patients, the problems of suspected familial colon carcinomas are discussed with special reference to screening policy and treatments. Upon identification of hereditary colon cancer (Lynch syndrome). treatment of the patient should consist of extensive resection and, if the patient is younger than 50 years, life-long careful follow-up. PMID- 2586810 TI - A remarkable subhepatic tumour. AB - Although foreign-body pseudotumours are not particularly rare, the diagnosis is not often considered. The case history is presented of a patient with a surgical gauze left after a cholecystectomy performed 23 years before. The incidence of these pseudotumours and the variety of clinical pictures in relation to the condition are described. PMID- 2586811 TI - Rectal bleeding as the first clinical symptom of renal cell carcinoma. PMID- 2586812 TI - A useful help for controlling haemorrhage during subtotal splenectomy. PMID- 2586813 TI - The natural course of postoperative ileus following abdominal surgery. AB - Postoperative ileus is a normal, transient condition following surgical procedures of the abdomen. The restoration of gastrointestinal motility was studied in 50 patients who had abdominal surgery. The motility was evaluated by means of physical signs and clinical symptoms. Physical signs, such as bowel sounds, passage of first flatus and defecation, occurred on relatively constant moments in the postoperative period and did not depend on the type of operation. In the patients who had rectopexy, flatus and defecation passed significantly later, probably due to existing defecation problems before the operation. The moment of resumption of a normal diet varied greatly. None of the physical signs had a predictive value with regard to postoperative nausea or vomiting. No relation could be demonstrated between the moment of removal of the nasogastric tube and the volume of gastric aspirate drained by the tube. The period of postoperative drainage of the stomach in comparable patient groups differed strongly from ward to ward. More attention for nasogastric tube management following abdominal surgery seems desirable. Early removal of the tube is possible in most patients and diminishes unnecessary discomfort. PMID- 2586814 TI - Ganglion cells and retinopetal fibers of the larval lamprey retina: an HRP ultrastructural study. AB - The ultrastructure of ganglion cells and centrifugal fibers of the larval lamprey retinas were studied using horseradish peroxidase (HRP) as a marker. Larval ganglion cells were found both in the inner nuclear layer and the inner plexiform layer of the differentiated retina, and also were present in the undifferentiated retina. Direct photoreceptor-ganglion cell contacts and the presence of centrifugal fibers are described for the first time in the lamprey. The centrifugal fibers contact directly with ganglion cells in this species. PMID- 2586815 TI - Proctolin activates a slow, voltage-dependent sodium current in motoneurons of the lobster cardiac ganglion. AB - The two-electrode voltage-clamp technique was used to study the ionic basis of the slow depolarization caused by the neuropeptide proctolin. At negative membrane potentials, proctolin caused a dose-dependent slow inward current. This current reversed and became outward at membrane potentials positive to 0 to +20 mV. Current-voltage curves also showed the response to be voltage-dependent, with a reversal potential at positive membrane potentials. The response was blocked in sodium-free solutions. Solutions with reduced sodium concentration caused a shift of the reversal potential in a manner expected for a response that is largely sodium-dependent. We conclude that proctolin causes an inward current by increasing a voltage-dependent cation conductance that is predominantly permeable to sodium. PMID- 2586816 TI - Increased firing of locus coeruleus neurons associated with preparatory set in rats. AB - The activity of locus coeruleus (LC) neurons was studied during the performance of a reaction-time task with warning. Seventeen cells were tentatively identified as LC neurons using two criteria: (1) Relative location from the mesencephalic trigeminal (Me5) neurons, which have large-amplitude bursting discharges synchronized with masticatory movements. (2) The presence of an antidromic response to the stimulation of the dorsal pathway. Of these 17 cells, 16 neurons showed intense and consistent firing during the period between the warning stimulus and the response. Neither the stimuli nor the lever pressing movements alone were accompanied by such a change, suggesting that increased firing occurs in association with preparatory set. The one remaining neuron of the 17 cells showed no change with the task performance. It is supposed that only the 16 homogeneous neurons belong to the LC. PMID- 2586817 TI - Endogenous adenosine can reduce epileptiform activity in the human epileptogenic cortex maintained in vitro. AB - The effects induced by adenosine and some related compounds upon Mg2+-free epileptogenesis were studied in slices of human epileptogenic neocortex maintained in vitro. Extracellular recordings revealed stimulus-induced and spontaneous epileptiform activity within 1-2 h of perfusion with Mg2+-free medium. A 30-90% decrease of the frequency of occurrence of spontaneous epileptiform discharges was induced by 40-50 microM adenosine while the analog 2 Cl-adenosine exerted a depressant effect (greater than 75% reduction in frequency of occurrence) at 0.3-3 microM. 2-Cl-adenosine also depressed stimulus-induced epileptiform responses and often blocked spontaneous epileptiform activity. Similar effects were seen during bath application of the adenosine uptake inhibitor nitrobenzylthioinosine (10-50 microM) indicating that endogenous adenosine can by itself influence epileptogenicity. Our data demonstrate that in the human epileptogenic neocortex a purinergic mechanism can control Mg2+-free epileptiform activity. PMID- 2586818 TI - Thermoperiod and photoperiod interact to affect the phase of the plasma melatonin rhythm in the lizard, Tiliqua rugosa. AB - Rhythms of plasma melatonin levels were determined in lizards (Tiliqua rugosa) subjected to 6 h thermocycles (6 h, 33 degrees C thermophase; 18 h, 15 degrees C cryophase) placed at 4 different phases of a 12 h photocycle (12 h light: 12 h dark). The peak of the melatonin rhythm was either shifted at different rates, or inhibited by the light phase of the photocycle, depending upon the phase relationship between the thermocycle and the photocycle. The results indicate that the pineal organ of ectotherms is part of a circadian pacemaker system, transducing photothermal environmental information into a neurochemical signal. PMID- 2586819 TI - Localization of muscarinic receptors on somatostatin-like immunoreactive neurones of the newborn guinea pig urinary bladder in culture. AB - Muscarinic receptors were localized on cells cultured from the detrusor muscle of the newborn guinea pig urinary bladder by autoradiography using the irreversible muscarinic antagonist [3H]propylbenzilylcholine mustard, before being immunostained with an antibody to somatostatin. Many mononucleate and binucleate intramural neurones immunoreactive for somatostatin were observed (60-75% of the total population), a subpopulation of which (40-60%) expressed muscarinic receptors. Autoradiographic grains were distributed over the whole cell body surface and the entire length of the neurites. An even distribution of silver grains was also seen on cultured smooth muscle cell surfaces, but not on other cell types present in the culture preparations. The demonstration of muscarinic receptors on specific neuropeptide-containing cells in culture is consistent with the existence of specialized cholinergic, intraganglionic circuits within the bladder wall, and suggests that somatostatin may also be involved in the integration and/or modulation of bladder function. PMID- 2586820 TI - Further evidence for Renshaw inhibition in man. A combined electrophysiological and pharmacological approach. AB - Experiments involving the acute administration of a central cholinergic substance (L-acetylcarnitine) were performed on 6 healthy subjects to obtain additional evidence that the electrophysiological method developed by Bussel and Pierrot Deseilligny in 1977 does actually assess recurrent inhibition in man. In all the subjects, the drug further decreased the amplitude of a test H reflex (H') following a conditioning H reflex (H1). The amount of this supplementary inhibition was found to be related to the size of H1 reflex. Experimental evidence is also presented that H' reflex supplementary depression is not contaminated by homonymous Ib effects. It is concluded that the method effectively tests the excitability of Renshaw cells in man. PMID- 2586821 TI - Eye-movement representation in the frontal lobe of rhesus monkeys. AB - We systematically explored the frontal eye field (FEF), the supplementary eye field (SEF), and nearby regions of the frontal cortex to establish the limits of these or possible adjacent eye-movement fields in macaque monkeys. We found a medio-laterally oriented band of saccadic eye-movement sites that extended from the inferior limb of the arcuate sulcus onto the medial surface of the hemisphere and into the dorsal bank of the cingulate sulcus. Two parts of this region may be outside previously described eye-movement areas. We conclude that eye movements are more broadly represented in the frontal lobes than previously described: either the SEF extends into the dorsal bank of the cingulate sulcus and laterally to the arcuate sulcus, or there are more than two frontal eye-movement fields. PMID- 2586822 TI - Inhibition of protein synthesis in the dentate gyrus, but not the entorhinal cortex, blocks maintenance of long-term potentiation in rats. AB - We examined whether the critical protein synthesis for maintenance of perforant path long-term potentiation (LTP) takes place in the dentate gyrus or the entorhinal cortex. Field potential recordings were made of responses in the dentate gyrus to stimulation of the perforant path in urethane-anaesthetized rats. Anisomycin (10 micrograms) injected into the dentate gyrus, but not the entorhinal cortex, 1 h prior to tetanization led to nearly complete decay of perforant path LTP of the excitatory postsynaptic potential (EPSP) within 3 h. Intra-dentate injection of neither actinomycin D (a mRNA synthesis inhibitor) nor boiled anisomycin affected LTP maintenance over 6 h. These results suggest that the proteins necessary for the maintenance of LTP over 6 h are synthesized in the dentate gyrus from already existing mRNA without involving protein synthesis in the cell bodies of the afferent fibres. PMID- 2586824 TI - Acute reduction of extracellular sodium differentially affects receptor-mediated and K+-induced calcium uptake in PC12 pheochromocytoma cells. AB - Using a rapid-quench method to measure 45Ca2+ uptake into PC12 cells in suspension, we have studied basal, carbachol-stimulated and K+-induced Ca2+ uptake under control conditions [( Na+]o = 130 mM) and in the presence of acutely lowered extracellular sodium concentration [( Na+]o = 65 mM). Acute reduction of [Na+]o stimulates basal and K+-evoked Ca2+ uptake, but reduces net carbachol stimulated uptake. Since total Ca2+ uptake measured in the presence of carbachol under control and low [Na+]o conditions is unchanged, the reduction in carbachol stimulated uptake is due to the increase in basal uptake induced by low [Na+]o. These results reconcile apparently conflicting data regarding a specific Na+ requirement for nicotinic acetylcholine receptor-mediated responses in PC12 cells and adrenal chromaffin cells and suggest a mechanism for loss of nicotinic acetylcholine receptor (nAChR) responsiveness to agonists under low Na+ conditions. PMID- 2586823 TI - Chronic estrogen effects on 5-hydroxytryptamine-mediated responses in hippocampal pyramidal cells of female rats. AB - Intracellular recording techniques were used to assess the effect of chronic estrogen treatment of ovariectomized (OVX) rats on CA1 pyramidal cell properties and serotonin (5-HT)-mediated responses in the dorsal hippocampus. The magnitude of the 5-HT1A-mediated hyperpolarization and concomitant change in membrane resistance elicited by 15 microM 5-HT was greater in pyramidal cells from OVX rats treated with estrogen (OVX + ES) than in pyramidal cells from OVX rats. Estrogen treatment did not alter the cellular membrane properties or the reduction in AHP amplitude elicited by 15 microM 5-HT. The modulation of 5-HT neurotransmission by estrogen may contribute to variations in mood which are associated with the menstrual cycle. PMID- 2586825 TI - In vitro synaptic maturation. AB - Cocultures of spinal cord neurons and muscle cells taken from rat embryos were used for in vitro reproduction of embryonic synapses. This system did not display the synaptic maturation characteristics of postnatal development: decreased multiple innervation and the presence of a developed subneural apparatus. Studies on cultures consisting of 3 cell types (muscle cells, nerve cells, Schwann cells), or on co-cultures (muscle cells, nerve cells), in the presence or absence of a monoclonal antibody directed against an antigen from Schwann cells, have shown that Schwann cells participate in synaptic maturation and in the elimination of superfluous synapses. The synapses were visualised for optical microscopy by co-localisation of acetylcholinesterase (AChE) spots and acetylcholine receptor (AChR) clusters. PMID- 2586826 TI - Developmentally expressed O-acetyl ganglioside GT3 in fetal rat cerebral cortex. AB - Monoclonal antibody M6704, established against the chick neural tube, was shown to recognize a trisialosyl residue, NeuAc alpha 2-8NeuAc alpha 2-8NeuAc alpha 2-3 R of C-series gangliosides. Using this antibody, the developmental changes of C series gangliosides in fetal rat cerebral cortex have been examined. Two dimensional thin layer chromatography (TLC) enzyme-immunostaining analysis revealed that alkali treatment resulted in a great increase in GT3 that amounted to more than 85% of the total GT3 detected. The alkalilabile form was easily degraded to form GT3 by the action of the receptor-destroying enzyme of influenza C virus, sialate O-acetylesterase, indicating that the antigen was most probably 9-O-acetyl-NeuAc containing GT3. The ganglioside was highly enriched at the 14th gestation day, gradually decreased, and was not detected in adult rat cerebral cortex. PMID- 2586827 TI - Muscarinic regulation of spontaneously active medial vestibular neurons in vitro. AB - We examined the effects of cholinergic agonists and antagonists on spontaneously occurring action potentials extracellularly recorded from medial vestibular nucleus (MVN) neurons in rat brainstem slice preparation to elucidate the cholinergic mechanism involved in excitation. Addition of carbachol (10(-6)-10( 5) M) and muscarine (10(-6)-10(-5) M) into the bath dose-dependently increased the spontaneous firing rate, while nicotine (10(-5)-10(-4) M) had no effects. Acetylcholine (10(-6)-10(-5) M) in the presence of physostigmine (10(-7) M) also increased the firing rate in a dose-dependent manner. Conversely, atropine (10( 8)-3 x 10(-7) M) slightly decreased the firing and dose-dependently inhibited the carbachol-induced increase in the firing rate. These results suggest that the firing rate of spontaneously active MVN neurons are regulated by acetylcholine via muscarinic receptors. PMID- 2586828 TI - Cloning of cDNAs encoding a rat neuropeptide immunologically related to salmon melanin-concentrating hormone. AB - In order to identify the neuropeptide related to melanin-concentrating hormone (MCH) synthetized by neurons of the posterior hypothalamus in the mammals, we have screened rat hypothalamus and rat brain cDNA expression libraries using MCH antiserum. We isolated 5 distinct immunopositive recombinants with cross hybridizing cDNA inserts. One of them hybridized to RNAs exclusively located in neurons stained by the same antiserum, as seen by successively performing in situ hybridization and then an immunocytochemical technique on the same section. Sequencing of this MCH-like cDNA is in progress. PMID- 2586830 TI - A dissociation procedure for mammalian taste cells. AB - A procedure for dissociating viable taste cells from the rodent tongue was described. After the tongue was excised, the foliate and circumvallate papillae from the posterior region were blocked to small pieces and incubated for 2-3 h in a calcium-free salt solution containing the enzyme papain. The pieces were then transferred to a Ca-replete medium. The epithelium was easily removed from the underlying muscle and gland tissue with forceps. Light mechanical agitation caused single cells, epithelial and gustatory, to dissociate from the keratinized epithelium. Taste cells were identified by their morphology. Their viability was assessed with the patch clamp technique in the whole cell recording mode. This procedure should enhance the electrophysiological study of gustatory transduction mechanisms. PMID- 2586829 TI - Adrenergic input from medullary ventrolateral C1 cells to the nucleus raphe pallidus of the cat, as demonstrated by a double immunostaining technique. AB - By means of a double immunostaining technique using unconjugated cholera-toxin B subunit (CTb) as a retrograde tracer combined with phenylethanolamine-N methyltransferase (PNMT) immunohistochemistry, we demonstrated that the nucleus raphe pallidus of the cat receives a major projection from the ventrolateral part of the rostral medulla corresponding to the nucleus paragigantocellularis lateralis and the ventrolateral medullary reticular formation just caudal to it. We further showed that nearly 60% of the total CTb-labeled cells in this region are immunoreactive to PNMT. These double-labeled cells constitute one-third of the total PNMT-immunoreactive cells. PMID- 2586831 TI - Endocytosis of cationized ferritin by rat photoreceptors. AB - Endocytosis by rods of the rat retina was studied at the ultrastructural level with cationized ferritin. Endocytosed ferritin was found within all photoreceptor subdivisions except the outer segment. Within the cell, synaptic vesicles, lysosomes and a variety of other membrane-bound organelles including the axonal agranular reticulum contained ferritin. These findings indicate that surface membrane and materials bound to surface membrane are recycled to form synaptic vesicles, that a portion of the captured membrane and extracellular material enters a lysosomal pathway, and that endocytosed materials can be retrogradely transported to the myoid region of the photoreceptor. PMID- 2586832 TI - Postnatal neurogenesis in the nucleus sphericus of the lizard, Podarcis hispanica. AB - Autoradiography was used to demonstrate the genesis and migration of cells in the nucleus sphericus of perinatal, juvenile and adult lizards, Podarcis hispanica (Sauria, Lacertidae). Following intraperitoneal injections of [3H]thymidine (5 microCi/g b. w.) and survival times of 1, 7, 18 and 28 days, labelled cells were found in the ependyma, marginal layer and mural layer of the nucleus sphericus in specimens of all ages. After short survival times, most labelled cells were located in the ependymal layer. Longer survival times resulted in labelling of cells mainly in the mural layer. At intermediate survival times, a substantial number of labelled cells was also found in the marginal layer. The time course of labelling suggests that neuronal proliferation takes place in the ependyma surrounding the ventricle. Subsequently, the newly formed neurons migrate centripetally and are recruited into the mural layer. PMID- 2586833 TI - Early neurohistopathological changes of canine lumbosacral spinal cord segments in ischemia-reperfusion-induced paraplegia. AB - Mapping the canine lumbosacral spinal cord neurons damaged by ischemia reperfusion after high thoracic aorta ligation was performed using the Nauta degenerating method. Highly Nauta-positive perikarya of the long ascending projection systems in the 4th to 6th dorsal layer, interneurons in the 7th layer and motoneurons in the 8th and 9th layers in L3-S3 segments subjected to 30 min of ischemia and 30 min of reperfusion were localized and their laminar distribution was specified. Spastic paraplegia fully developed 2 days postoperatively after 30 min of aortic ligation is neurohistopathologically characterized by occurrence of enlarged Nauta-positive boutons with prevailing localization in the 4th to 8th layer of the gray matter. PMID- 2586835 TI - Medical waste program. PMID- 2586836 TI - Reasonable litigation assistance. PMID- 2586834 TI - Retinopetal cells exist in the optic tectum of steelhead trout. AB - The existence of retinopetal cells in the tectum of various teleost fishes as been claimed by several authors. Others, however, have been unable to verify such observations and attribute the findings of retrogradely labelled tectal cells to methodological problems. In this study cobalt-lysine and HRP have been used as neuronal tracers. Evidence is provided for the presence of retinopetal cells in the tectum of steelhead trout. Dendritic arborizations of some of the cells are extremely elaborate. In salmon no such findings were made. PMID- 2586837 TI - Blood donor must answer questions. PMID- 2586838 TI - Aortic balloon valvuloplasty. AB - Fifty-eight patients with severe aortic stenosis underwent successful aortic balloon valvuloplasty. The mean aortic valve gradient was reduced from 65 +/- 22 to 32 +/- 13 mmHg with symptomatic improvement. The procedure is an effective palliative procedure for patients with high surgical risk. PMID- 2586839 TI - The gift of life. AB - A young woman suffers from chronic mental illness, characterized by depression and suicidal impulses. With the implementation of lithium therapy, along with her determination, the patient achieves a state of stabilization. PMID- 2586840 TI - Chondrosarcoma and malignant lymphoma. AB - We describe two primary malignancies occurring simultaneously. The coexistence of chondrosarcoma and malignant lymphoma, small lymphocytic type (MLSL) (WDLL) is a rare occurrence. In this case, the untreated malignant lymphoma appears to have increased the aggressiveness of the chondrosarcoma through its adverse effect on the host's immune system. PMID- 2586841 TI - Bilateral adrenal hemorrhage. AB - The diagnosis of bilateral adrenal hemorrhage, a potentially fatal complication of anticoagulation therapy, can be made by computed tomography (CT) scan. We present a case of a heparinized patient with CT examination of the adrenal glands before and after the onset of acute adrenal insufficiency. PMID- 2586842 TI - Decision support systems: essential for quality administrative decisions. PMID- 2586843 TI - Selecting, implementing, and evaluating patient classification systems: a measure of productivity. PMID- 2586844 TI - Mercy Hospitals and Health Services of Detroit. PMID- 2586845 TI - Nursing in mental health. PMID- 2586846 TI - Medical-surgical nursing: Mount Carmel. PMID- 2586847 TI - Perspectives on costing nursing. PMID- 2586848 TI - NCNIP's system of the future: a call for accountability, revenue control, and national data sets: National Commission on Nursing Implementation Project. PMID- 2586849 TI - The McAuley experience with changing compensation within the context of a professional nursing practice culture. PMID- 2586850 TI - Integrating professional values, quality practice, productivity, and reimbursement for nursing. PMID- 2586851 TI - Archives of ophthalmology, Volume 8, 1932: Experimental cataract in vitamin G deficiency. PMID- 2586852 TI - Energy expenditure and the control of body weight. AB - Patients who have bulimia or who formerly were obese have a reduced metabolic rate and are predisposed to weight gain or regain. PMID- 2586853 TI - Season, latitude, and ability of sunlight to promote synthesis of vitamin D3 in skin. AB - Season, latitude, skin pigmentation, and life-style factors affect the availability of ultraviolet radiation from the sun for photoconversion of 7 dehydrocholesterol to previtamin D3 in the skin of humans. PMID- 2586854 TI - Urbanization and breastfeeding in the Philippines. AB - Differences in extent and duration of breastfeeding between rural and urban areas in the Phillippines increased between 1973 and 1983. PMID- 2586855 TI - Cholecystokinin and gastric emptying. AB - Protease inhibitors and peptone, which are potent stimulators of cholecystokinin release, slow gastric emptying time in rats. The cholecystokinin antagonist L364,718 reverses this effect. PMID- 2586856 TI - From one addiction to another: life after alcohol and drug abuse. AB - Once the alcoholic or drug addict has stopped drinking or using drugs, other addictive behaviors are frequently adopted. These factors must be considered in planning the overall recovery program. Substances likely to be used to excess include nicotine, caffeine, sugar, chocolate, nutritional supplements and medicinal herbs. Addictive behaviors adopted by recovering persons include eating disorders, exercise and body building, workaholism, and dependency on one's own adrenalin. Breaking the cycle of addiction requires commitment to a program of self-growth and becoming responsible for one's actions. PMID- 2586857 TI - Precocious puberty: identifying early sexual development. AB - Primary care providers should have the ability to identify normal and abnormal variations of sexual development in children. The incidence of precocious puberty is approximately one child in every 10,000 children in the United States. While etiologies vary, precise differential diagnosis is essential because it will determine the course of treatment required. New forms of therapy using long acting luteinizing releasing factor agonists are currently being investigated. Developmentally appropriate explanations for affected children regarding the diagnosis and treatment plan are a crucial component of care. Ongoing educational and emotional support for the child and family are essential as they learn to cope with early sexual development. PMID- 2586858 TI - Dealing with AIDS and the adolescent population. AB - AIDS is a lethal disease that poses a major threat to adolescents who engage in high-risk behaviors such as unsafe sex and IV drug use. It is estimated that 21 percent of individuals diagnosed with AIDS in their 20s were infected as teens. Public health officials maintain that education is the best strategy for limiting spread of the disease; however, unique development attributes of adolescents present barriers to this approach. These barriers can be breached through a variety of interactive educational strategies designed specifically for the adolescent audience. The critical messages to get across are that "safe sex is condom protected sex," and "don't share needles." PMID- 2586860 TI - Concerns expressed about PATH program. PMID- 2586859 TI - Radon: detection and treatment. AB - Within the last few years, natural radon exposure in non-industrial settings, primarily homes, has become a health concern. Research has demonstrated that many homes throughout the United States have radon concentrations much higher than the legal federal limits set for miners. Thousands of unsuspecting people are being exposed to high levels of radiation. It is estimated that up to 15 percent of lung cancers are caused from radon. This is a significant health risk. With basic knowledge of the current information on radon, a primary health care provider can address patients' radon concerns and make appropriate referrals. PMID- 2586861 TI - Employment tips offered for new practitioners. PMID- 2586862 TI - Coping with conflict. PMID- 2586863 TI - Some golden rules of everyday nursing. PMID- 2586864 TI - Great tips for setting priorities. PMID- 2586865 TI - 7 ways to sharpen your leadership skills. PMID- 2586866 TI - How to chart effectively. PMID- 2586867 TI - Nurses need nurturing too. PMID- 2586868 TI - Managing your patients' adverse reactions to narcotics. PMID- 2586869 TI - The secret in Sally's eyes. PMID- 2586870 TI - Monitoring a blood transfusion. PMID- 2586871 TI - Who should make life-or-death decisions for an A.I.D.S. patient? PMID- 2586872 TI - Insights on death and dying. PMID- 2586873 TI - A case of stolen authority. PMID- 2586874 TI - Action stat! Ruptured ectopic pregnancy. PMID- 2586875 TI - Acute pulmonary edema. How to respond to a crisis. PMID- 2586876 TI - Caring for A.I.D.S. patients: the stress will be on you. PMID- 2586877 TI - Monitoring vital sign changes in children. PMID- 2586878 TI - L.E.A.D. drugs for cardiac emergencies. Clinical close-up on epinephrine. PMID- 2586879 TI - Rescuing a multiple trauma victim. PMID- 2586880 TI - Avoiding the pitfalls of rehabilitation at home. PMID- 2586881 TI - Survival skills for the R.N. student. PMID- 2586882 TI - Ruby was a multifaceted challenge. Nursing grand rounds. PMID- 2586883 TI - Assessing flank pain. PMID- 2586885 TI - How to handle criticism. PMID- 2586884 TI - Myths and facts about electrolytes. PMID- 2586886 TI - Think you're powerless? Think again. PMID- 2586887 TI - Remembering the basics: 14 keys to staff nursing. PMID- 2586888 TI - A dream for Brady. PMID- 2586889 TI - A.I.D.S. update. PMID- 2586890 TI - Insights on death and dying. PMID- 2586891 TI - Better discharge planning for patients with A.I.D.S. PMID- 2586892 TI - Fine-tuning your percussion techniques. PMID- 2586894 TI - Action stat! Ethylene glycol poisoning. PMID- 2586893 TI - Sleep in the C.C.U.--the impossible dream? PMID- 2586895 TI - Your legal guide to safe nursing practice. PMID- 2586896 TI - Dispute over A.I.D.S. issue. PMID- 2586897 TI - Early pregnancy loss--what you can do to help. PMID- 2586898 TI - L.E.A.D. drugs for cardiac emergencies. Clinical close-up on atropine. PMID- 2586899 TI - Mr. Crenna couldn't rest--and neither could we. PMID- 2586900 TI - Not for specialists only--caring for patients with spinal cord injuries. PMID- 2586901 TI - Making a critical difference with C.A.V.H. PMID- 2586902 TI - Using personal protective apparel. PMID- 2586903 TI - Chemotherapy experts. PMID- 2586904 TI - Alzheimer's disease. Safety begins at home. PMID- 2586905 TI - It's time. PMID- 2586906 TI - A question of assault and battery. PMID- 2586908 TI - Take care with the Add-Vantage system. PMID- 2586907 TI - What Jim found in his stocking. PMID- 2586909 TI - A.I.D.S. update. PMID- 2586910 TI - Myths & facts ... about oxygenation. PMID- 2586911 TI - Ectopic pregnancy pointers. PMID- 2586912 TI - Understanding transtracheal oxygen delivery. PMID- 2586913 TI - Staff nurses vs. agency nurses--seeing it from both sides. PMID- 2586914 TI - Clinical close-up on dopamine. PMID- 2586916 TI - New drugs: update 89. PMID- 2586915 TI - "Poor Mabel" was trying to shut out the world. PMID- 2586917 TI - New remedies: check the facts. PMID- 2586919 TI - Testing blood glucose levels. PMID- 2586918 TI - A job to do. PMID- 2586920 TI - A circle of care. PMID- 2586921 TI - Test your knowledge of medical/surgical nursing, Part 3. PMID- 2586922 TI - Insights on death & dying. PMID- 2586923 TI - High-gear nursing: how it can run you down and what you can do about it. PMID- 2586924 TI - 7 tips to make you a better leader. PMID- 2586925 TI - Convert paramedics into RNs? PMID- 2586926 TI - Nurses & discharge planning. PMID- 2586927 TI - Your statement is contradictory concerning the substitution of registered nurses with licensed practical nurses. PMID- 2586928 TI - Illiteracy in healthcare. PMID- 2586929 TI - Going back. PMID- 2586930 TI - Discipline without punishment--Part I. PMID- 2586931 TI - Litigation stress in nurses. PMID- 2586932 TI - Developing an integrated nursing case management model. PMID- 2586933 TI - Case management: what's in a name? PMID- 2586934 TI - Work measurement and nursing time standards. PMID- 2586935 TI - Quality measurement: quick, easy and unit-based. PMID- 2586937 TI - Nursing risk management. PMID- 2586936 TI - Decision making styles of nurses. PMID- 2586938 TI - Controlling the budgetary plan. PMID- 2586939 TI - Toward positive attitudes and feelings. PMID- 2586940 TI - Central processing comes home. PMID- 2586941 TI - The PRN plan: professional reimbursement for nurses. PMID- 2586942 TI - A young dentist's point of view. PMID- 2586943 TI - Women in dentistry. PMID- 2586945 TI - Organized dentistry's role in the changing practice modalities. PMID- 2586944 TI - Recognition of craniomandibular disorders. A legal and professional responsibility. PMID- 2586946 TI - Are dentists next? PMID- 2586947 TI - Papanicolaou smear screening interval and risk of cervical cancer. AB - The efficacy of Papanicolaou smear screening intervals of longer than 1 year is uncertain. Ninety-two symptomatic cases of invasive cervical cancer diagnosed between 1978-1983 in western Washington were identified with a population-based tumor registry. Using a random-digit-dialing technique, 178 controls from the same geographic area were selected. A structured telephone interview was used to ascertain screening history and risk factors for cervical cancer. The mean interval between papanicolaou smears in the 10 years preceding diagnosis (cases) or the reference date (controls) was calculated. The risk of squamous cell cervical cancer was increased 3.9 times (95% confidence interval 1.2-12.3) for women with Papanicolaou smears at 3-year intervals compared with women with annual screening. For women who had not had a Papanicolaou smear in the preceding 10 years, this risk increased 12.3 times (95% confidence interval 2.5-60.6). For screening intervals of 2 years, the risk of cervical cancer (all cell types) was not increased (relative risk 1.01; 95% confidence interval 0.43-2.37). The presence of well-known risk factors for cervical cancer did not modify these results. These data suggest an increasing risk of cervical cancer if Papanicolaou smear screening intervals exceed 2 years. PMID- 2586948 TI - Magnetic resonance evaluation of double uteri. AB - A total of 18 infertile patients with hysterosalpingographic diagnosis of bifid uterus underwent magnetic resonance imaging (MRI) and subsequent laparoscopy or laparotomy to evaluate the capability of MRI to differentiate among the various classes of the malformation. Magnetic resonance imaging identified both bicornuate uteri correctly, both didelphic uteri, nine of the 12 partial septate uteri, and both complete septate uteri. The method demonstrated a sensitivity of 100% and a specificity of 78.6% in demonstrating cervical prolongation of the spur. Compared with laparoscopy, MRI is less expensive and less invasive, and can also be performed in patients with extensive adhesions. However, it has the disadvantage of not providing information on tubal conditions or on the presence of minimal and mild endometriosis. PMID- 2586949 TI - What is the significance of the human chorionic gonadotropin value in ectopic pregnancy? AB - Surgical and pathology data were analyzed with the quantitative serum hCG values from 131 patients with tubal pregnancies. The hCG value correlated with both the size and contents of the eccyesis. Patients with ruptured tubal pregnancies had significantly greater serum hCG levels than did those with intact tubal gestations. Isthmic tubal pregnancies were associated with more frequent rupture and larger amounts of hemoperitoneum than were pregnancies in the ampullary segment of the tube. Tubal rupture with hCG values below 100 mIU/mL occurred in two isthmic pregnancies but in no ampullary pregnancies. With serum hCG levels below 300 mIU/mL, significant hemorrhage did not occur unless the tube was ruptured. Half of the patients had hCG levels sufficient to use a vaginal sonographic hCG discriminatory zone to assist in the diagnosis. A maximum of 15% of tubal pregnancies may be diagnosed by ultrasonographic detection of adnexal cardiac activity. A serum hCG assay sensitive to 10 mIU/mL will detect nearly all tubal pregnancies. The hCG level frequently has diagnostic value when used in conjunction with vaginal sonography. At hCG levels of 100 mIU/mL or less, tubal rupture is very unlikely for ampullary, but not for isthmic, tubal pregnancies. PMID- 2586950 TI - Efficacy of different starting doses of oxytocin for induction of labor. AB - One thousand twenty inductions of labor by amniotomy and continuous infusion of oxytocin at the Royal Women's Hospital were reviewed. Three different starting rates of infusion of oxytocin were used by altering the concentration to 2, 5, or 10 U/L. There was no difference in success of induction as measured by induction to-delivery interval or by rate of vaginal delivery using higher initial concentrations of oxytocin. Higher pre-induction Bishop scores were associated with shorter labors and more vaginal deliveries. This study was retrospective and nonrandomized, but within these limits it suggests that "low-dose" oxytocin infusion is effective for induction of labor and may be associated with fewer hazards than are higher doses. PMID- 2586951 TI - Increased neutrophil activation in diabetic pregnancy and in nonpregnant diabetic women. AB - Human neutrophil elastase may be a mediator of vascular damage, and enhanced neutrophil reactivity could contribute to the susceptibility of pregnant diabetic women to vascular complications. Elevated plasma levels of neutrophil elastase will reflect neutrophil activation in vivo. The aim of this study was to determine whether neutrophil activation occurs in uncomplicated diabetic pregnancy. We studied 30 normal nonpregnant women, 20 nonpregnant diabetic women, 32 nondiabetic women with normal pregnancies, and 17 insulin-requiring pregnant diabetic patients. Plasma neutrophil elastase was measured by radioimmunoassay. There was a significantly higher concentration of plasma neutrophil elastase in normal pregnant women compared with the nonpregnant group (P less than .001). The nonpregnant diabetic group had significantly higher concentrations than the normal nonpregnant group (P less than .002). The pregnant diabetic group had significantly higher concentrations than the nonpregnant diabetic group (P less than .001) and the normal pregnant group (P less than .05). The high concentrations of plasma neutrophil elastase may contribute to the greater sensitivity of pregnant diabetic patients to vascular complications. PMID- 2586953 TI - Reliability of fetal buttock blood sampling in assessing the acid-base balance of the breech fetus. AB - This prospective investigation was undertaken to compare fetal buttock capillary blood pH and umbilical artery and vein pH in fetuses presenting by the breech. The study group comprised ten term patients with singleton fetuses in the frank breech presentation who met established criteria for vaginal breech delivery. All patients had a normal labor pattern. Eight fetuses had a normal fetal heart rate tracing and two had severe variable decelerations during the second stage of labor. We obtained capillary blood for pH measurement from the fetal buttock within 15 minutes of delivery. Immediately after delivery, we collected arterial and venous blood samples from the umbilical cord for measurement of pH. In all fetuses, there was a highly significant correlation between fetal buttock capillary blood pH and umbilical artery pH (r = 0.96; P less than .001) and umbilical vein pH (r = 0.88; P less than .001). We conclude that measurement of pH in capillary blood obtained from the fetal buttock provides accurate assessment of the acid-base status of the breech fetus. PMID- 2586952 TI - Cocaine abuse during pregnancy: correlation between prenatal care and perinatal outcome. AB - Cocaine abuse during pregnancy has been associated with increased perinatal morbidity and mortality regardless of the quantity or quality of prenatal care. In this study, we tested the hypothesis that among cocaine-abusing women delivering at the same institution, those receiving comprehensive prenatal care have better perinatal outcome than those receiving little or no prenatal care. Between January 1, 1984 and July 1, 1987, 120 pregnant women who abused cocaine received multidisciplinary prenatal care in the Perinatal Center for Chemical Dependence of Northwestern University (group 1). During this same period, we identified 21 cocaine-abusing parturients at our institution who were not enrolled in the Perinatal Center for Chemical Dependence and who received little or no prenatal care (group 2). Control subjects were selected from the general obstetric population for comparison. Data from these two groups were compared with each other and with matched control pregnancies. Group 2 pregnancies had lower mean gestational age at delivery, lower mean birth weight, and a higher incidence of preterm delivery than group 1 pregnancies. Furthermore, groups 1 and 2 were significantly different from control pregnancies for these parameters. We conclude that comprehensive prenatal care may improve outcome in pregnancies complicated by cocaine abuse; however, the perinatal morbidity associated with cocaine abuse cannot be eliminated solely by improved prenatal care. PMID- 2586954 TI - Survival and morbidity of extremely premature infants based on obstetric assessment of gestational age. AB - To provide current clinical information for obstetric decision-making and perinatal management, we present early morbidity and mortality data for extremely premature infants based on obstetric assessment of gestational age. We reviewed the records of 141 live-born infants with birth weights of 1600 g or lower born at a university hospital level III neonatal intensive care unit between January 1986 and April 1988, whose gestational ages estimated by antenatal obstetric evaluation were between 24-29 completed weeks. Neonatal survival to 30 days ranged from 20% at 24 weeks to 94% at 29 weeks. Chronic lung disease was present at 30 days in all infants born at 24 weeks' gestation, decreasing to 13% of infants born at 29 weeks' gestation. Rates of severe intraventricular hemorrhage (grade 3 or 4) ranged from 100% at 24 weeks to 7% at 29 weeks. These data represent a significant increase in survival and a decrease in early morbidity compared with those form similar populations before 1986. PMID- 2586955 TI - The management of severe erythroblastosis fetalis by fetal transfusion: survival of transfused adult erythrocytes in the fetus. AB - The survival of adult erythrocytes transfused into the fetus was measured after intravascular and/or intraperitoneal transfusion. We performed 80 fetal transfusions on 20 severely anemic fetuses, 18 of whom survived. The survival of adult erythrocytes in the fetal circulation was similar to that in the adult circulation and did not depend on the route of transfusion, gestational age, or presence of hydrops. Eighty percent of blood transfused into the fetal peritoneal cavity appeared in the fetal circulation. PMID- 2586956 TI - Intravenous pancuronium bromide for fetal neuromuscular blockade during intrauterine transfusion for red-cell alloimmunization. AB - Intravenous pancuronium bromide was administered into the umbilical cord by funipuncture to effect temporary fetal paralysis. Neuromuscular blockade was achieved in 12 fetuses undergoing a total of 34 intrauterine procedures for the treatment of severe red-cell alloimmunization. The same initial dose of 0.2 mg/kg fetal weight estimated by ultrasound was used in all cases, but anemic fetuses did not resume movement for prolonged periods. A relationship among fetal hematocrit, adjusted dose, and duration of paralysis was described by the equation: Duration (hours) = 5.24 + 10.30 adjusted dose (mg/kg) - 0.16 hematocrit (%) (R2 = 0.49; P less than .001). Intravenous pancuronium was found to be a safe and effective method for cessation of fetal movement during intrauterine procedures. PMID- 2586957 TI - Does fetal acidosis develop with maternal glucose infusion during normal labor? AB - The actual effects of glucose infusion on fetal acid-base status were studied during 125 normal deliveries in which plasma glucose and acid-base parameters were determined after maternal infusion of either 10% glucose or Ringer's solution. After 80 minutes, mean (+/- SD) plasma glucose levels were significantly higher in the glucose group (N = 59) than in the Ringer's group (N = 66), both for the mother (183.6 +/- 46.8 versus 95.3 +/- 18.0 mg/dL) and the fetus (108.4 +/- 41.4 versus 64.8 +/- 16.2 mg/dL). Fetal plasma lactate concentrations did not differ between the glucose and the Ringer's groups, but were significantly lower in the fetuses delivered by elective cesarean section in both groups. With glucose administration, fetal pCO2 was higher and pH values were lower than in the Ringer's group. However, the magnitude of acid-base status changes, indicated by both pH and pCO2 shifts (ie, the difference between umbilical artery and scalp values), failed to differ between the two groups. In fetuses with progressing hypoxia, no differences in any of the acid-base parameters were observed between glucose and Ringer's administration. These data indicate that at a glucose infusion rate of 30 g/hour, fetal acidosis, when it occurs, results from hypoxia rather than from maternal glucose administration. PMID- 2586958 TI - The effect on fetal growth of protozoan and helminthic infection during pregnancy. AB - This is a prospective study of 14,914 pregnant women conducted in Guatemala City, Guatemala. Stool samples were obtained from the studied patients before the first prenatal visit (mean gestational age 21.6 +/- 8.4 weeks) for the diagnosis of parasitic infections during pregnancy. Forty-four percent had at least one parasite detected, and 24% were infected with helminths. Ascaris lumbricoides was the most prevalent (14.5%). Infected mothers were less educated, had less adequate water and sanitary conditions, and had lower nutritional status. The incidence of intrauterine growth retardation (IUGR) increased with the number of parasitic species detected (up to two or more species, P less than .01). High levels of infection (greater than or equal to + +) were associated with an increased risk of IUGR for protozoa and helminths, except for Strongyloides stercoralis and Hymenolepis nana. Chronically malnourished women of short stature had significantly higher IUGR rates when infected with one or two or more species (P less than .01). Up to 10% of the IUGR rates may be attributed to parasitic infections among the malnourished women. PMID- 2586959 TI - Intraoperative evaluation of depth of myometrial invasion in stage I endometrial adenocarcinoma. AB - In patients with stage I endometrial adenocarcinoma, the incidence of pelvic and para-aortic lymph node metastasis is related to the grade of the tumor and the depth of myometrial invasion. Although the grade of the tumor may be predicted preoperatively by endometrial sampling, the depth of myometrial invasion cannot be determined until after the uterus has been removed. Although complications have been attributed to lymph node sampling, failure to perform the procedure in patients at risk for nodal metastasis may result in underdiagnosis of extrauterine disease, leading to inadequate therapy. Gross visual examination of the cut surface of the tumor at the time of hysterectomy accurately determined the depth of myometrial invasion in 135 of 148 prospectively studied patients (91%) (P less than .001). The sensitivity of the test was 0.71, the specificity was 0.96, and the positive predictive value was 0.80. Intraoperative assessment of the depth of myometrial invasion is a simple, inexpensive, and useful technique for selecting those patients with stage I endometrial adenocarcinoma who might benefit from selective para-aortic lymphadenectomy. PMID- 2586960 TI - Pelvic exenteration, University of Michigan: 100 patients at 5 years. AB - One hundred patients undergoing pelvic exenteration (total 69, anterior 13, posterior 18) at the University of Michigan Medical Center from 1964-1984 are reported. All patients were followed for at least 5 years or until time of death. The overall cumulative survival was 66% at 3 years and 61% at 5 years. The age of the patients ranged from 21-74 years (median 53). The type of pelvic neoplasm included squamous cell of the cervix, 57; adenocarcinoma of the cervix, nine; squamous cell carcinoma of the vulva, 12; squamous cell carcinoma of the vagina, eight; vaginal sarcoma, four; adenocarcinoma of the vagina, one; adenocarcinoma of the endometrium, four; uterine sarcoma, four; and adenocarcinoma of the ovary, one. The cumulative 5-year survival was significantly related to the presence of metastatic disease to the regional lymph nodes (8% 3-year and 0% 5-year survival), time interval from primary diagnosis to exenteration (within 1 year 44%, 1-10 years 60%, and over 10 years 95%), and cell type (squamous cell 68%, sarcoma 62%, and adenocarcinoma 26%). Patients with squamous cell carcinoma of the cervix (N = 57) had a cumulative 5-year survival of 73%, compared with nine patients with adenocarcinoma of the cervix, who had a 22% 5-year survival. No significant difference in survival existed for the type of exenteration, original stage of squamous cell cervical carcinoma, size of recurrent squamous cell lesion, or age of the patient. Early or late complications occurred in 49 patients. Two patients died in the postoperative period. Small-bowel obstruction was the most common complication seen in this series. PMID- 2586962 TI - Level of reading difficulty in the American College of Obstetricians and Gynecologists patient education pamphlets. AB - Written educational and informational materials are an important and potentially useful means to complement verbal instructions, assure that consent for tests and procedures is informed, and enhance compliance with treatment. In specialties other than obstetrics and gynecology, many of these materials have been found to be written at a level of difficulty above the reading ability of the intended audience. The SMOG formula was used to assess the level of reading difficulty of all 74 English-language patient education pamphlets developed by The American College of Obstetricians and Gynecologists (ACOG) Committee on Patient Education. Sixty-one of these pamphlets are written at a reading difficulty level of 11th grade or higher. Although the mean reading education level in the United States is at grade 12.6, the mean literacy level is at or below eighth grade. With the exception of one ACOG pamphlet written specifically for low-readability audiences (p-063, Birth Control Pills), all the pamphlets are written at a level higher than the literacy level of many women. The information is unlikely to be understood if it is written above the reading ability of the intended audience. This disparity is accentuated for health-education materials because scientific and technical terms further reduce the level of comprehension. The SMOG formula is a simple means to ensure that educational materials are written at a level appropriate for the intended audience. PMID- 2586961 TI - Monitoring the course of cervical carcinoma with the squamous cell carcinoma serum radioimmunoassay. AB - Serum samples were collected from 611 gynecologic patients for measurement of squamous cell carcinoma antigen levels using the Abbott Laboratories squamous cell carcinoma antigen radioimmunoassay kit. Sixteen of 83 patients (19.3%) with cervical dysplasia and 72 of 135 (53.3%) with primary or recurrent cervical carcinoma had levels above 2.4 ng/mL. In contrast, only seven of 373 women (1.9%) without genital tract squamous cell intraepithelial neoplasia or carcinoma had squamous cell carcinoma antigen levels above 2.4 ng/mL. Fifty-six patients with cervical cancer were followed for correlation of squamous cell carcinoma antigen levels to disease course, and 20 had persistent or recurrent disease after therapy; rising squamous cell carcinoma antigen levels predicted disease in 15 of these 20 patients with recurrence (13 of 15 with elevated pre-treatment levels and two of five with normal pre-treatment levels). Rising squamous cell carcinoma antigen levels preceded the clinical detection of disease in ten patients by a mean of 4.6 months (range 2-7.5 months); in the remaining five, squamous cell carcinoma antigen levels were elevated only when disease recurrence was documented. Although measurement of squamous cell carcinoma antigen levels is not a sensitive screening method for cervical cancer (sensitivity 53.3%), the test has good specificity (94.3%); the majority of patients with false-positive elevations had other genital tract squamous cell neoplasias. The squamous cell carcinoma antigen assay may be a useful aid for monitoring the disease course of cervical carcinoma. PMID- 2586963 TI - Survey of maternal-fetal medicine subspecialists: professional activities, job setting, and satisfaction. AB - We analyzed the job setting, professional activities, and satisfaction of subspecialists in maternal-fetal medicine. A two-page questionnaire was mailed to all members of the Society of Perinatal Obstetricians. The results were analyzed by multiple regression and multivariate analysis. Of 603 questionnaires mailed, 496 (80%) were returned; 70% of all certified maternal-fetal medicine subspecialists responded. The job setting of respondents was university hospital based faculty in 66%, community hospital-based salaried in 15%, private practice in 10%, and other in 9%. The average percent of professional time devoted to each area was as follows: clinical work, 57% of all professional time; research, 18%; administrative, 15%; and educational, 11%. Time distribution, volume of hysterectomies, and number of peer-review publications were the only significant differences among job settings. For university hospital-based faculty, the time distribution was 50% clinical, 23% research, 16% administrative, and 11% educational. For community hospital-based salaried physicians, it was 63% clinical, 10% research, 16% administrative, and 11% educational; for private practice, it was 84% clinical, 7% research, 5% administrative, and 6% educational. Types of activities of maternal-fetal medicine subspecialists included ultrasound (75% of respondents, mean 436 studies per year), gynecologic procedures (71% of subspecialists, volume of 8.7 hysterectomies per year), genetic procedures (83%; 125 procedures per year), research (87%), recent peer review publications (80%), grants (40%), and medicolegal reviews (64%). Ninety five percent had a medical-school faculty appointment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2586964 TI - Unrecognized thrombocytopenia and regional anesthesia in parturients: a retrospective review. PMID- 2586965 TI - Ethical dilemmas in fetal echocardiography. PMID- 2586966 TI - Characteristics of normal labor. PMID- 2586967 TI - Digoxin-like immunoreactive factor in twin and pregnancy-associated hypertensive pregnancies. PMID- 2586968 TI - [Occupational diseases of the eye and their prevention at industrial plants in Zaporozhye]. AB - A study of the character, causes and incidence of professional diseases of the eye in 3,588 workers of four industrial plants has shown that the most frequent causes of the disease are the action of dust, thermal reaction, chemically active products of production, the usage of obsolete equipment, low technology, insufficient measures of individual and collective protection of the eye. In workers with a length of service to 5 years the incidence of diseases made up 2.4%, and more than 10 years--10.8%, at the average. Economic losses due to one sick person achieved 3,017.3 doubles, at the average. Recommendations for improvement of prophylaxis of professional diseases of the eye are given. PMID- 2586969 TI - [Autonomic ophthalmologic aspects of occupational environmental health effects on seamen aboard transport and commercial vessels]. AB - Complex investigations of the functional state of the visual analyser and vascular system has been carried out in 150 practically healthy members of a screw working in extreme conditions of a long-term voyage. It is shown that approximately one month after the beginning of the voyage the observed members of the screw developed signs of functional changes in visual acuity, light sensitivity, intraocular pressure level, hemodynamic indices. The main tendency is seen in some rise of the level of the studied indices within the first three six months with their subsequent fall. Possible mechanisms of changes developing in conditions of long-term voyage, especially the role of the state of the vegetative nervous system, and possibilities of prophylactic measures stimulating the weakening of dysfunctional disturbances are discussed. PMID- 2586970 TI - [Visual fatigue as an occupational pathology problem in ophthalmology]. AB - A study of incidence and peculiarities of visual fatigue in workers of visually strained, in particular, precision labour (about two thousand subjects) has shown a connection between visual fatigue and the character and conditions of work. This allows to consider visual fatigue from positions of professional pathology. The attention is drawn to necessity to consider results of scientific researches in the field of industrial ophthalmology, ophthalmological ergonomics and professional pathology of the eye as well as in their further active development. PMID- 2586971 TI - [The results of research on visual fatigue in children by determining the perception time of a sequential color contrast]. AB - The paper analyses results after a study of visual fatigue by means of determining the perception time of a color successive contrast in children, aged from 10 to 13 years, before and after intensive dosed visual load. The revealed high percentage of visual fatigue in children (40.4-52.5%) is likely to be connected with the fact that the study was made in spring time when signs and body asthenization, avitaminosis are expressed. It was found that perception of a color successive contrast in children with eye myopization is shorter as compared with children with stably normal visual acuity. PMID- 2586972 TI - [The administration of preparations into the vorticose vein in the combined therapy of severe forms of uveitis]. AB - The paper describes positive results after treatment of 15 patients with severe forms of uveitis by means of administering preparations into the portal vein of the eye. The method was substantiated by a series of experimental investigations. The treatment of patients with uveitis was prescribed when common therapy within a week and in some cases--a month after beginning of treatment proved to be ineffective. In 8 eyes with endogenous uveitis visual acuity rose from 0.06 +/- 0.4 at admission to 0.28 +/- 0.7 at discharge. In 4 patients with supposed enucleation of the eye the proposed method allowed to stop the inflammatory process. This method permitted to shorten the term of the patients stay at the hospital by 6.8 days. No complications during the treatment of recurrences in remote period were recorded. PMID- 2586973 TI - [The effectiveness of combining scleroplasty with ultrasonic activation of the filtering zone of the anterior chamber angle in progressive myopia]. AB - A new method for treatment of progressive myopia is developed that includes simultaneous action on both components of the leading pathogenetic link of myopization: "intraocular pressure--durable properties of the sclera". The method includes a combination of sclera-enhancing operations (administration of auto- or allotissue into the sub-Tenon's space of the posterior segment of the eye) with microhypotensive action (ultrasonic activation of the filtration zone of the anterior chamber angle). A comparison of results after 30 operations of common retrosclerosealing with those after 30 operations of retrosclerosealing in combination with acoustic hypotensive action (the follow-up period--4 years) has shown that in patients with acoustic hypotension the level of intraocular pressure fell by 2.9 mm Hg, this being 1.2 mm Hg higher than after common retrosclerosealing. In case of common retrosclerosealing myopia progressed in 10% of patients and in its combination with acoustic hypotensive action further progression of myopia was not recorded. PMID- 2586974 TI - [The significance of immunologic factors in the pathogenesis of uveal glaucoma]. AB - A study of the immunologic status in 60 patients with uveal glaucoma, of them 32 patients with chronic uveitis and 28 patients with uveopathies has revealed changes in the immunologic status in these two groups of patients: the reduction of the number of T-lymphocytes and T-suppressors, a tendency to reduction of the number of T-helpers and R-lymphocytes; sensibilization of leucocytes in these two groups of patients to antigens of the choroid, the retina, the iris and to antigens of the trabecular tissue: reduction of indices of migration with these antigens in experiment as compared with control investigations. A conclusion is made that the presence of the signs of immunodeficiency and signs of sensitization to autoantigens make it advisable to use immunocorrective and desensitizing preparations for treatment of patients with uveal glaucoma, especially in pre- and postoperative period. PMID- 2586975 TI - [The eye function of various contingents of the adult population based on data from the first stage of universal outpatient care]. AB - At the first stage of ophthalmologic dispensarization of population 1287 rural (535 men) and 1328 urban (648 men) inhabitants have been examined. A comparative analysis of pathology of the eye, the state of visual acuity in different age contingents of rural and urban population, aged from 17 to 79 years, has shown pathology of the eye among rural population in 56.88 and among urban--in 35.17% of cases. Normal visual acuity (with correction) was observed more frequently (921.09 per 1000 eyes) in persons living in a town than in inhabitants of villages (779.33 per 1000 eyes). This index is remarkably lower in persons above 49 years of age because of development of such diseases as senile cataract, pathology of the retina and the optic nerve, etc. Practical blindness among rural population was observed much rarer (6.78 per 1000 eyes) than among rural population (8.95 per 1000 eyes). The incidence of the same pathology in similar age groups of different contingents of adult population was different. This should be considered when organizing dispensary observation over rural and urban population. PMID- 2586976 TI - [Rhythmic cyclicity of monocular perception in binocular fixation under haploscopy]. AB - The paper describes results after a study of rhythmic cyclicity of monocular perception in 341 students with normal visual functions in bifixation for far and for near. It was found that cyclicity of monocular perceptions (biorhythms) in healthy persons with binocular vision is the same in bifixation for far both in soft and hard haploscopic conditions. In bifixation for far in haploscopic conditions the rhythms of monocular perceptions are more frequent than for far. Both for far and for near the rhythms of binocular vision are more frequent in women than in men. PMID- 2586977 TI - [The pathochemistry of the diabetic process in the eye based on data on experimental hyperglycemia (alloxan diabetes)]. AB - The paper describes results after a study of pathochemical disturbances of diabetic hyperglycemia on a model of alloxan diabetes. Sugar and amino nitrogen contents in the aqueous humor of the anterior chamber, anterior and posterior segments of the crystalline lens, the iris, ciliary body, choroid and the retina were studied and the data obtained were compared with quantitative contents of sugar and amino nitrogen in the eliminate from the eyes of experimental animals. High amounts of sugar and amino nitrogen, infrequently exceeding 2-3 times in controls, were found to appear in the aqueous humor of the anterior chamber, the crystalline lens, the vitreous body. In all tests the sugar and amino nitrogen contents in the posterior segment of the lens was 10-12% higher than in its anterior segment. The data obtained about accumulation of sugar and amino nitrogen mainly in tissues and media of the eye (the lens, the vitreous) affected by diabetic process already at its early stages widen the knowledge about pathogenesis of the process and peculiarities of its pathochemistry. PMID- 2586978 TI - [Secondary cataract in the intraocular correction of aphakia]. AB - A study of peculiarities of secondary cataract formation in implantation of posterior chamber intraocular lenses in experiment on 60 rabbit eyes has shown that, besides the known factors of secondary cataract formation, a great role belongs to inflammatory reaction of all segments of the uveal tract leading to appearance of a transudate in the anterior chamber of the eye as well as to development of adhesions of the iris and ciliary body processes with the lens capsule, along which stromal elements of these segments of the uveal tract actively migrate. PMID- 2586979 TI - [Depth visual function and the relative accommodation reserves of patients before and after keratotomy]. AB - Reserves of relative accommodation and thresholds of remote vision have been investigated in 60 patients with myopia of different degree before radial keratotomy and 1.5-2.0 years after the surgery. It was firstly established that the state of accommodation and remote vision for near before surgery influences the stability of the obtained postoperative effect. This fact should be considered when planning keratotomy. A conclusion is made that for patients with reserves of accommodation of the positive part not lower that 2.0D and the threshold of remote vision for near not higher than 7 mm keratotomy is not advisable. PMID- 2586981 TI - [The possible reasons for diagnostic errors in paralytic strabismus]. PMID- 2586982 TI - Private judging ... has its time come? PMID- 2586980 TI - [Disability as a consequence of ocular pathology in the Ukrainian SSR]. PMID- 2586983 TI - Curing and caring: from two to eighteen. PMID- 2586985 TI - Clinic to study pediatric AIDS cases. PMID- 2586984 TI - The children nobody wants. PMID- 2586986 TI - Hospital vogue. PMID- 2586987 TI - Private judging in Ohio. PMID- 2586989 TI - Drug wars and drugstores. PMID- 2586988 TI - Are steroids muscling in on your patients? PMID- 2586990 TI - Assessing your risk exposure. PMID- 2586991 TI - Ambulatory cassette EEG in epilepsy evaluation. AB - The economy and effectiveness of 24-hour ambulatory cassette EEG (AEEG) are increasingly recognized. We reviewed 735 AEEGs recorded between 1983 and 1989. These findings suggest that AEEG may confirm the ictal original of attacks in patients with known epilepsy, and may improve the yield of abnormality in epileptics with normal interictal EEG. Focal slowing may be seen less well on AEEG, and the yield of AEEG is low in random sampling of patients with infrequent or nonspecific symptoms. PMID- 2586992 TI - Caput medusae. PMID- 2586993 TI - Witch doctors and AIDS. PMID- 2586994 TI - Developing the vast wasteland. PMID- 2586996 TI - The forgotten underserved. PMID- 2586995 TI - Clochards, penner or rogues. PMID- 2586997 TI - Local health departments: the medical community's best-kept secret? PMID- 2586998 TI - The Fels study: research infinitum? PMID- 2586999 TI - Medical videos. Glitzy new teaching tools for physician and patient. PMID- 2587000 TI - Are you laser-literate? PMID- 2587001 TI - Reducing the risk of liability with the help of hospital staff. PMID- 2587003 TI - Follow-up of breast cancer patients. AB - The existing follow-up standard for breast cancer patients has been reviewed by a representative trial involving 1,004 curatively treated patients, who underwent surgery between 1977 and 1987. The objective of the study has been to establish whether intensive diagnostics of recurrences and metastases will lead, as a result of the follow-up, to life prolongation or improvement of life quality, and which methods will be adequate to achieve this goal. The analysis has shown that metastases are recognized only insignificantly earlier, and that improvement of survival is not achieved. The results of the trial have led to a recommendation for an effective follow-up programme for breast cancer patients, with emphasis on subtle case history data and exact clinical investigations. PMID- 2587002 TI - The role of surgery in the combined treatment of locally advanced breast cancer. AB - Sixty patients with stage IIIA and IIIB breast cancer have been treated with a combined modality approach including induction chemotherapy, surgery and adjuvant chemotherapy: 74.5% of patients achieved an objective response after 3 cycles of induction chemotherapy, and 98.3% of patients were rendered disease-free after induction chemotherapy and surgery or radiotherapy; at 4 years, actuarial survival and disease-free survival are 71.5% and 43%, respectively. These results are significantly better than our historical control, and locally advanced breast cancer must now be considered a curable disease when treated with an aggressive multimodal approach. PMID- 2587004 TI - Phase II trial of combination chemotherapy with fluorouracil (F), doxorubicin (A), and cisplatin (P) (Fap) in hormonally resistant metastatic prostatic adenocarcinoma. AB - From October 1985 to December 1986, 25 patients with advanced prostatic carcinoma were entered in a phase II trial and were administered fluorouracil (F) 600 mg/m2, on days 1 and 2, doxorubicin (A) 40 mg/m2, on day 1, and cisplatin (P) 90 mg/m2, on day 1, every month. The response was evaluated after three cycles of chemotherapy according to National Prostatic Cancer Project criteria. There were no complete remission, 1 partial remission, 13 stabilizations, 11 progressions. Toxicity was assessed using WHO criteria. Alopecia and vomiting were universal; there were 11 grade 1 anemias, 2 aplasias, and 1 grade 1 renal toxicity. A FAP regimen appears to exert a marginal effect in advanced prostatic carcinoma. PMID- 2587005 TI - Influence of fetal calf serum in combination with pharmacological doses of progesterone or estradiol on proliferation and cell cycle kinetics of cultured mammary cancer cells. AB - We describe an original method to monitor clonal cell density (hyperplasia) and the cell cycle kinetics of neoplastic cells simultaneously. We thus characterize the in vitro influence of two different types of fetal calf serum (FCS), defined as FCS-S and FCS-I, on the progesterone- or estradiol-induced effect on proliferation and cell cycle kinetic parameters of the MXT mouse and MCF-7 human mammary cancer cell lines. The two sera were treated with dextran-coated charcoal. The FCS-S serum showed a stimulatory influence on MXT and MCF-7 growth, whereas FCS-I was devoid of any clear-cut influence. The cells were cultured on glass coverslips, placed in Petri dishes containing either a control or a hormone added medium, fixed for histology and submitted to the Feulgen reaction, which allows selective and quantitative (stoichiometric) staining of DNA. Proliferation and cell cycle kinetics were analyzed on the same sample of cells by means of the SAMBA 200 cell image processor. Our results show that steroid-mediated effects were dramatically modulated according to the type of serum used. Furthermore, they also show that pharmacological doses of progesterone or estradiol decrease MXT cell growth by at least two different mechanisms: the first is related to cell cycle kinetics, i.e. an inhibition of the cells into the S phase, while the second remains unknown but seems to be cell cycle independent. High dose estradiol, but not progesterone, induced the same inhibitory influence on the MCF 7 cells. PMID- 2587006 TI - The relation of ATP response in CaNT tumours after X-irradiation to varying tumour volumes. AB - The response of adenosine-5'-triphosphate (ATP) levels in implanted murine CaNT tumours, 2.5 h after 10 Gy X-rays (100 kVp) was measured in vivo using various tumour volumes. It is probable that the concentration of ATP, which increased after X-irradiation, plays a major role in energy supply associated with cellular repair processes. Nevertheless, when ATP levels in irradiated tumours were plotted against tumour volume in the range 150-550 mm3, a monotonically decreasing relation was found. This is interpreted as reflecting the degree of hypoxia and changes in the tumour metabolic status. In addition effects of vascular occlusion and artificial hypoxia have been studied after clamping the tumour for 15 min, followed by a radiation dose of 10 Gy and maintaining the clamp for a further 2.5 h. This showed a drastic decrease in the ATP levels 2.5 h after the irradiation, compared with controls in normoxia. It is thought this is due to induction of hypoxia which is produced throughout the tumour volume, resulting in the depletion of cellular ATP. This implies that the clamped tumour cells are less capable of generating a metabolic response following radiation damage. PMID- 2587007 TI - Value of aceto-orcein squash preparations in the cytogenetic study of solid tumours. AB - The value of aceto-orcein squash preparations as a routine initial step in the cytogenetic study of solid tumours is pointed out. This simple procedure allows a rapid evaluation to be made of various characteristics of the tumour, including the ploidy level, as well as a definitive assessment of nuclear phenomena including the incidence of X-chromatin bodies. Evaluation of the latter in normal as well as tumour cells led to the discovery of unsuspected congenital sex chromosome anomalies in two patients in this laboratory. PMID- 2587008 TI - [The spatio-temporal distribution of single-stranded breaks in nuclear DNA in sections of clawed toad embryos during gastrulation and neurulation]. AB - Spatial and temporal pattern and quantities of nicks in nuclear DNA during gastrulation and neurulation was studied using nick-translation in sections of Xenopus laevis embryos. Specific changes in the number of nicks in different mesoderm and ectoderm regions were detected during embryogenesis. Dorso-ventral gradient of nuclear labelling was observed in mesoderm and inner ectoderm layer of early and middle gastrula. The gradient was inverted during transition from gastrula to neurula. At the same time dorso-ventral (in mesoderm) and ventro dorsal (in outer ectoderm layer) gradients of nuclear labelling were increased. The intensity of nuclear labelling in all parts of embryo as a whole was remarkably higher during neurulation as compared with gastrulation. Dorso-ventral gradient of nuclear labelling was observed in mesoderm and ectoderm during neurulation. A connection between the nicks and differentiation status of the cells during early embryogenesis in amphibians is suggested. PMID- 2587009 TI - [Mutant gene expression in mouse aggregation chimeras. 8. The effect of the white gene on coat pigmentation]. AB - Aggregation of mouse embryos produced 11 chimaeras Miwh/+C/C----+/+c/c and 8 chimaeras +/+C/C----+/+c/c (control). Chimaerism was detected by mosaicism of coat retinal pigment epithelium and by electrophoretic pattern of glucose phosphate isomerase. All chimaeras showed a common pattern of pigmented and unpigmented hair regions that alternated as stripes of different length and width and extended from spine in lateral-ventral direction. However, white coat color predominated in Miwh/+C/C----+/+c/c chimaeras due to a higher proportion of unpigmented zones as well as to weakening of hair color in pigmented areas. Besides, distal regions of limbs were always unpigmented in Miwh/+C/C----+/+c/c chimaeras and completely or partially pigmented in +/+C/C----+/+c/c chimaeras. Pigmented hair regions are often located on the ventral trunk surface where the Miwh/+ heterozygotes usually had an unpigmented spot. The examination of hairs, taken from the same regions of gray coloration, revealed the presence of pigmented, unpigmented and mosaic hairs. The proportion of unpigmented hairs was much higher in Miwh/+C/C----+/+c/c chimaeras than in +/+C/C----+/+c/c chimaeras. The data obtained indicate that a single Miwh gene dose reduced proliferative activity of melanoblasts which resulted in weakening of coat pigmentation. PMID- 2587010 TI - [Casein kinase type II during lens fiber differentiation in amphibians]. AB - cAMP-independent protein kinase activity of casein type was found in Rana temporaria eye lens. The highest activity was observed in "cortex" lens fibres, and decreased two-fold in lens epithelium. Minimum activity was found in lens "nucleus" fibres. Thus, protein kinase activity is characteristic of metabolically active differentiating lens cells. Enzyme fraction showed almost complete binding to the immobilized RNA. The enzyme was inhibited by heparine, phosphorylated casein (but not histones). It could use either ATP or GTP as a source of phosphate, and caused modification of serine and threonine residues in casein molecule. The protein kinase from lens epithelium and cortex was purified 6,000-7,000-fold and was identified as a type II casein kinase. PMID- 2587011 TI - [Neural differentiation of ectodermal explants of the early gastrula from Rana temporaria under the action of various mitogens and kainic acid]. AB - The following mitogens: concanavalin A (con A), phytohemagglutinin (PHA), hydra growth factor (HGF) as well as neurotoxic agent kainic acid, caused neural differentiation (N) effects differed in value and also in character of dependence on concentration of the agent. The lowest effective concentration of con A was 75 micrograms/ml (15% neural differentiation, treatment during 3 h), and the effect reached maximum of 50-60% at 100-200 micrograms/ml. Con A concentration 50 micrograms/ml showed no effect but after 1% rabbit gamma-globulin was added, 17% neural differentiation was detected. N-effects observed after treatment of explants with con A (200 micrograms/ml, 3h) at 2 degrees and 21 degrees were similar (58 and 42% respectively). Minimum PHA concentration used (6 micrograms/ml, 18h) led to neural differentiation in 5% of explants. N-effect of PHA increased along with the concentration of the lectin and was most pronounced at 25 micrograms/ml. However, further increase in concentration (up to 200 micrograms/ml) resulted in decrease of its N-effect to 13%. At 12 micrograms/ml PHA exerted not only neural differentiation, but also lens-inducing (32%) action on the ectoderm. N-effect of HGF (2.5, 25 and 250 micrograms/ml) was lower as compared with the maximum effects of con A and PHA (30-35%). No correlation of HGF inducing action with its concentration was observed. Kainic acid showed weak N-effect (20-30%) at 1 and 10 micrograms/ml. Higher concentration (100 micrograms/ml) had no N-effect, but in 27% of explants "free" lentoids were found. Oubain (10(-3) and 10(-4) M) and HEPES (20 mM) did not affect the differentiation of explants. PMID- 2587012 TI - [The first cycle of DNA replication in parthenogenetic mouse embryos]. AB - Dynamics of the first cell cycle in parthenogenetic mouse embryos derived from ethanol-activated eggs was studied using 3H-thymidine. DNA synthesis starts within 5 h and is terminated within 10 h after activation: it lasts ca. 6 h. Changes in the intensity of 3H-thymidine incorporation and in the distribution of radioactive label between haploid and diploid parthenogens were observed. 3H thymidine was shown to incorporate into pronucleoli of diploid parthenogens and late-labeled heterochromatin blocks were bound in both diploid and haploid pronuclei. The structure of the first cell cycle in parthenogenetic and normal embryos is discussed. PMID- 2587013 TI - [Changes in the distribution of adenylate cyclase activity in PC 12 cells under the influence of nerve growth factor]. AB - Changes in distribution of adenylate cyclase in PC 12 cells under the influence of nerve growth factor (NGF) have been studied using cytochemical methods. The adenylate cyclase activity was predominantly associated with the plasma membrane. In cell cultures without NGF the activity was revealed on the contacting surfaces of cell aggregates; single grains of reaction product were revealed on exposed cell surface only in cultures with a high cell density. One day after administration of NGF, the adenylate cyclase activity on exposed cell surface increased, and three days later the whole cell surface was covered with lead sediment. The enzyme activity was also revealed in growth cones, filopodia and microcytospheres. The role of adenydlate cyclase system in neuron-like differentiation of PC 12 cells is discussed. PMID- 2587014 TI - [The transplantation of rabbit embryos]. AB - Criteria of morphological assessment of zygote quality and various transplantation conditions have been studied to achieve implantation in the host female and obtain the offspring. The data obtained indicate that implantation of 10-15 zygotes with light homogeneous cytoplasm and distinct pronuclear membrane per recipient female may be regarded as optimal conditions. PMID- 2587015 TI - Life span of human corneal endothelial cells in long-term cultures. AB - Human corneal endothelial cells (HCEC) were isolated from excised corneas of adult donors in the age range of 28-70 years, and successfully grown for 10-12 passages. Moreover, one cell line, that had been established from a 45-year-old donor, was further passaged at defined split ratios in order to determine the proliferative life span of the HCEC isolated from donors of this age group. PMID- 2587016 TI - Abstracts of the 29th meeting of the Association for Eye Research. Albena, Bulgaria, September 25-29, 1988. PMID- 2587017 TI - Therapy of corneal erosions and 'dry eye' with Solcoseryl and Vitasic eye drops. AB - A comparative study of Solcoseryl eye drops versus Vitasic eye drops has been carried out under controlled conditions (randomized and double-blind) on a total of 94 patients. 52 had corneal erosion, 30 had dry eye syndrome, 8 cases could not be evaluated. In addition, 2 eyes with photophthalmia were treated with Vitasic and 2 showing keratitis with Solcoseryl. There were no adverse reactions other than 2 instances of stinging with Solcoseryl and 1 case of severe irritation after Vitasic. The patients were examined on days 0, 1, 3 and 7. Results showed a consistent superiority of Solcoseryl eye drops in respect to speed of healing of corneal erosions and moistening of the cornea in the 'dry eye' syndrome which reached statistical significance in some parameters. PMID- 2587018 TI - Light and electron microscopic retinal findings in Leigh's disease. AB - Funduscopic and retinal light- and electron-microscopic findings are described in an infant with progressive neurologic deterioration leading to death. Brain autopsy findings were consistent with Leigh's disease. The retinal mitochondria showed marked degenerative changes, the cristae were almost completely destroyed and electron-dense material filled a major part of the cavity. These changes are typically described in the late stages of mitochondrial diseases but have not been described before in retinal mitochondria in a patient with Leigh's disease. PMID- 2587019 TI - In vivo quantitation of autofluorescence in human retinal pigment epithelium. AB - We measured autofluorescence of the macula with fluorophotometry to evaluate age related changes in human retinal pigment epithelium. Examined in this study were 35 aphakic eyes of 25 patients, ranging in age from 52 to 87 years, after uneventful intracapsular cataract extraction and 21 normal phakic eyes of 20 patients, ranging in age from 9 to 29 years. Autofluorescence at the macula of aphakic eyes increased in an age-dependent manner (r = 0.514; p less than 0.01) as follows: 15.0 ngEq/ml for the sixth decade (n = 1), 17.2 +/- 4.2 for the seventh decade (n = 11), 21.3 +/- 3.6 for the eighth decade (n = 16) and 24.6 +/- 2.7 for the ninth decade (n = 7). We believe that the autofluorescence originates mainly from lipofuscin in the retinal pigment epithelium, and that the autofluorescence enhanced with age reflects the accumulation of lipofuscin. PMID- 2587020 TI - A case of metastatic optic nerve head and retinal carcinoma with vitreous seeds. AB - Metastasis directly to the optic nerve head without choroidal involvement is rare. We report a case of metastatic adenocarcinoma of the optic nerve head and retina with vitreous seeds which was observed in a 45-year-old Japanese male. The primary site of the lesion was clinically the upper lobe of the left lung. Tumor emboli were observed in the central retinal vein. Vitreous seeds appeared to have arisen from a necrotic area and papillary projections of the tumor. PMID- 2587021 TI - Vitrectomy for diabetic eye disease. The prognostic value of pre-operative electroretinography and visual evoked cortical potentials. AB - An investigation was carried out into the prognostic value of standard flash electroretinography (ERG) and visual-evoked cortical potentials (VECP) recorded for 87 diabetic eyes prior to vitrectomy. 95% of the eyes with a recordable ERG b wave achieved a post-operative visual acuity (VA) of 0.05 or better (positive predictive value), but only 35% of the eyes with a good post-operative VA had a recordable b-wave (sensitivity). The corresponding values for the ERG a-wave were 67 and 72%, and for the VECP 77 and 69%, respectively. A non-recordable b-wave in the ERG was associated with a poor visual outcome (VA less than 0.05) in 45% of cases (negative predictive value), and 97% of the eyes with a poor visual outcome had a nonrecordable b-wave (specificity). The corresponding values for the ERG a wave were 42 and 37%, and for the VECP 53 and 63%, respectively. Consequently, the odds ratio for an unfavourable visual outcome (VA less than 0.05) was greater for a non-recordable b-wave (15.7) than for a nonrecordable VECP (3.8) or a non recordable a-wave (1.5). Recordability of the b-wave gave the best prediction for attached macula. Extensive photocoagulation diminished all ERG and VECP amplitudes. Vitreous opacities had no significant effect on the ERG or VECP. PMID- 2587022 TI - [Visual status in diabetic maculopathy after central photocoagulation]. AB - Diabetic macular edema is shown to be treated successfully by central focal argon laser coagulation in most cases. Since February 1986, diabetic patients with macular edema were evaluated prospectively and treated by focal argon laser coagulation and/or grid pattern. A second group of diabetic patients with comparable macular edema and similar retinal changes was explored retrospectively. Visual acuity after treatment in relation to preoperative visual acuity was measured and statistically compared with visual acuity of the second group without laser treatment. The results show that laser treatment is important for stabilization of visual acuity but does not increase visual acuity beneath 0.2. Indications for treatment are discussed. PMID- 2587023 TI - A comparative study concerning the treatment of active toxoplasmic retinochoroiditis with argon laser and medication (follow-up 2-9 years). AB - Thirty-three eyes (i.e. 33 patients) with active toxoplasmic retinochoroiditis were treated and followed up for a 2 to 9 year period. The patients were divided into two groups. The first was treated with laser, while the second received medication. The division into two groups was made in order to discover possible differences between the two groups concerning success rate, time of regression of the lesion recurrences and complications. The study showed the following results: there was no difference as to the rate of overall success between the two groups. The laser produced no result in the cases where the active retinochoroidal lesion was larger than 2 disc diameters. The regression of the active lesion in the laser group was accomplished in 25-50 days, while in the medication group took 50 150 days. Recurrences after treatment were found in both groups. However, the starting point of recurrences differed in each group. PMID- 2587024 TI - Long-term observations of patients with acute retinal pigment epitheliitis. AB - Because of some authors presumptions that acute retinal pigment epitheliitis is not a distinct clinical entity but the early stage of other fundus diseases, the results of long-term observations of 5 patients with this disease are reported. The results of 6- to 7-year observations of these patients have shown that in none of them the fundus lesions developed into other retinal diseases. This indicates that acute retinal pigment epitheliitis is a distinct clinical entity. PMID- 2587025 TI - Effect and compatibility of isovolaemic haemodilution in the treatment of ischaemic and non-ischaemic central retinal vein occlusion. AB - In a prospective study, 48 eyes with non-ischaemic and 35 with ischaemic central retinal vein occlusion (CRVO) were treated by isovolaemic haemodilution (IHD). Two or more cardiovascular risk factors were present in 42% of patients with non ischaemic and in 69% of patients with ischaemic CRVO (p less than 0.025). Nevertheless, IHD in no case caused serious cardiovascular complications. Minor problems were short fainting spells in 5% and a general weakness in 16% of the haemodiluted patients. The effect of IHD was measured by determining the time of maximal venous filling (tmvf) in fluorescein angiographies. Lowering the packed cell volume to 32-35% accelerated the tmvf from 18.4 +/- 1.61 to 13.1 +/- 1.0 s (p less than 0.001) in eyes with non-ischaemic CRVO and from 24.5 +/- 1.2 to 14.8 +/- 1.3 s (p less than 0.001) in eyes with ischaemic CRVO. After 3 months, an increase in visual acuity had occurred in 27% of eyes with non-ischaemic CRVO and in 48.5% with ischaemic CRVO. These improvement rates could nearly be maintained after 1 year. 59% of eyes with non-ischaemic and 25% with ischaemic CRVO were able to read (visual acuity greater than or equal to 6/15) after 1 year. PMID- 2587026 TI - Prognosis and treatment of retinoblastoma. 105 cases treated at Institut Curie. AB - In a retrospective study of 105 retinoblastoma cases, the authors studied the clinical symptoms, survival and ocular conservations. The results are much better in case of early diagnosis. They discuss the therapeutic modalities in their institute and elsewhere. PMID- 2587027 TI - Esterase D analysis in familial retinoma and retinoblastoma. PMID- 2587029 TI - Histopathological evaluation for the prognosis of retinoblastoma. AB - In the present study histologic, clinical and follow-up data of 37 cases of retinoblastoma were statistically analyzed by means of a multivariate method. The evaluated histological parameters were: growth pattern, degree of differentiation, number of mitoses, presence of necrosis, pseudorosettes, blood vessel basophilia, calcification, extension to anterior chamber, invasion of optic nerve and ocular coats (choroid and sclera). The analysis was based upon the Cox proportional hazards regression model. Invasion of ocular coats proved to be highly correlated to the prognosis (p less than 0.0002). None of the other parameters showed a significant relation to survival. PMID- 2587028 TI - Retinoblastoma. Analysis of 75 cases and proposal for a new model of oncogenesis and tumor growth kinetics. AB - A series of 75 retinoblastoma patients were analyzed at the Institute of Ophthalmology, Siena, and a mathematical model for the 'nodule to cancer' transformation applied to it. The authors obtained data in disagreement with Knudson's 'two hit' hypothesis but fitting an alternative model of oncogenesis. This model is based on probabilistic arguments and a possible pattern of tumor growth and evolution is given in detail. PMID- 2587030 TI - Age and lateness of referral as determinants of extra-ocular retinoblastoma. AB - The risk of extra-ocular (EO) vs. intra-ocular disease was evaluated in a retrospective study of 158 consecutive cases of retinoblastoma (age range: birth to 113 months) admitted to the A.C. Camargo Hospital, Brazil, between January 1975 and December 1985. The risk of having EO disease was strongly dependent on the age at diagnosis and lateness of referral. The older the child at first admission the higher the risk of finding EO disease at diagnosis. This association was considerably more pronounced among sporadic unilateral cases. Patients with a history of longer duration of symptoms were more likely to exhibit EO disease than patients seeking medical attention within six months of the onset of the disease. This association seemed to be confounded by the genetic form of the disease as the increase in risk of EO disease appeared later among the germinal cases. Clinical stage and lateness of referral were the variables most associated with the survival experience of patients. PMID- 2587031 TI - Visual acuity outcome in isometropic hyperopia. AB - Refractive amblyopia may occur as a unilateral or bilateral condition. Although bilateral refractive amblyopia may account for 1 to 2% of all refractive amblyopia, there is little consistent information in the literature regarding isoametropic amblyopia resulting from bilateral hyperopia. Hence, this retrospective study investigated the prevalence of reduced aided acuity in patients aged 10 years and younger (mean age 3.97 years) with 5 D or more of isometropic hyperopia and considered the following factors that may influence visual acuity: (1) age at first correction; (2) magnitude of hyperopia; and (3) duration of refractive correction of the hyperopia. The results indicate that the majority of patients (87%) have aided acuity poorer than 6/6 at initial correction of refractive error. However, if the full hyperopic correction was worn for 1 year or longer, only 43% of these patients demonstrated acuity poorer than 6/6 and none showed acuity poorer than 6/12. The magnitude of the hyperopia appeared to have the greatest influence on the visual acuity outcome both at initial correction of refractive error and 1 year or longer after correction. Duration of correction also influenced the visual acuity outcome, but to a lesser extent than the magnitude of refractive error. In contrast, the age of first correction showed little correlation with visual acuity either at the time of first refractive correction or after a minimum of 1 year of correction. PMID- 2587032 TI - Optical design of intraocular lenses. III. On-axis performance in the presence of lens displacement. AB - The effect of intraocular lens shape on on-axis performance of model pseudophakic eyes was investigated, when lenses were displaced by tilting or decentration. Image quality criteria included an optimization procedure, spot diagrams, and the modulation transfer function (MTF). Displacement adversely affects image quality. With conventional lens shapes, the deterioration is either small or retinal image quality can be nearly restored to predisplacement levels by spectacle correction. Optimum lens shapes in the presence of decentration are close to being plano convex, with the more curved surface facing the cornea. Based on the results of this and previous studies, it is suggested that preferred shapes of intraocular lenses range from this plano-convex form to equi-convex. PMID- 2587033 TI - Physical characteristics and perceptual effects of "blue-blocking" lenses. AB - The transmission-optical properties of a "blue-blocking" lens and its influence on several aspects of human visual performance were assessed. Results showed that the lens was effective in absorbing ultraviolet and blue wavelengths and that its effects on contrast sensitivity and visual evoked potentials (VEP's) were similar to those produced by an equivalent neutral density (ND) filter. Although the lens did not alter stereopsis, it did produce severe color discrimination losses for normal and dichromatic subjects. PMID- 2587034 TI - Acanthamoeba culbertsoni and contact lens disinfection systems. AB - Acanthamoeba culbertsoni was used in this study inasmuch as its susceptibility to disinfection has not been examined. Although heat was found to be the most effective means of disinfection some cysts survived this procedure. Chlorhexidine exhibited a dose-response kill curve but the most effective concentrations are also corneo-toxic. Polyaminopropylbiguanide (0.00005%) has good effectiveness against the cyst but was not completely cidal at the dose tested. Thimerosal (0.002%) and hydrogen peroxide (3%) were found to be without effect. These findings should give contact lens practitioners guidelines for selecting a disinfection system for their patients. PMID- 2587035 TI - Eyeglasses and gender stereotypes. AB - Under the guise of forming impressions of a job applicant in a hiring interview, subjects rated a videotaped male or female stimulus person (SP) on several gender stereotypical and task relevant traits. In one condition, the SP's wore eyeglasses, and in the other condition they did not. Eyeglasses, especially when worn by the stimulus male, were associated with feminine stereotypes and positive task relevant attributes. The results were interpreted to suggest that men who wear eyeglasses may be the target of some negative social judgments but also redeeming task relevant attributes, whereas women who wear eyeglasses are more likely to be the target of only negative social judgments. PMID- 2587036 TI - Impact of health care trends on the practice of optometry. AB - Major trends occurring within the health care field will impact on the future practice of optometry. This report reviews several trends relating to cost containment, alternative delivery systems, population demographics, competition, corporate involvement in health care, and health promotion and wellness programs. Predictions are made regarding changes that may occur in optometric practice in the future in response to these emerging health care trends. PMID- 2587037 TI - The spiral curriculum in optometric education. AB - Optometric education should center around clinical training from the first year and develop within a spiral curriculum as far as possible. This does not eliminate the need for a layered curriculum where basic sciences are considered necessary to further learning but serves to make these sciences more applied and relevant to the study of optometry from the very beginning. A philosophy of science component requires to be integrated in the optometry teaching program so as to provide the student with as wide a range of thinking and problem-solving skills possible, in particular those which relate to optometry in general and clinical learning. Advanced technologies in the areas of computers and video materials as well as modern teaching strategies should be used to make paradigm changes in optometric teaching effective. PMID- 2587038 TI - Statistics notebook: population vs. sample. PMID- 2587039 TI - The ophthalmologist's role in licensing drivers. PMID- 2587040 TI - Legal blindness can be compatible with safe driving. AB - The objective of the study is to present evidence that some people with 20/200 visual acuity and a field of vision greater than 120 degrees can drive safely in the daytime at a speed of not more than 40 mph. Eight individuals with 20/200 visual acuity (legally blind) were tested for the distance at which they could recognize six traffic symbols. The study was done to see whether a person with 20/200 visual acuity could recognize symbols at a distance great enough to stop safely. Subjects recognized the symbols at a distance, determined by the U.S. Bureau of Public Roads, within which a vehicle traveling 40 mph could stop safely. PMID- 2587041 TI - A study of the relation between intraocular pressure and aqueous humor flow in the pigment dispersion syndrome. AB - Forty subjects with pigment dispersion syndrome with and without intraocular pressure (IOP) elevation were compared with 40 age-matched controls. Intraocular pressure, resistance to outflow, and the rate of flow of aqueous humor were compared. Eyes with higher IOP and higher resistance to outflow were found to have a normal rate of aqueous flow. The results are interpreted as demonstrating that moderate and chronic elevation of IOP in the adult human eye does not induce a chronic compensatory reduction of aqueous humor flow. PMID- 2587042 TI - Noncontact and contact pars plana transscleral neodymium: YAG laser cyclophotocoagulation in postmortem eyes. AB - Transscleral neodymium:YAG (Nd:YAG) laser energy (5 J), noncontact at 20 msec and contact at 0.5 sec exposure time, was applied to enucleated porcine and human eyes 3 mm posterior to the limbus. Coagulative pars plana lesions were noted in all cases. Related to focus and exposure time, noncontact lesions were larger, more homogeneous, and affected primarily the pigment epithelium, whereas contact lesions showed more full-thickness thermal effects, including sclera. Because the corona ciliaris was unharmed when laser applications were made 3 mm from the limbus, this commonly used clinical focus raises questions about cyclo "destruction." Future clinical research will have to show which phenotype of pars plana lesion correlates best with long-term lowering of pressure. PMID- 2587043 TI - Extraocular muscle imbalance after scleral buckling surgery. AB - Pneumatic retinopexy is advocated to treat some retinal detachment cases, in part to avoid the complication of induced strabismus sometimes associated with scleral buckling procedures (SBPs). Prospective evaluation of postoperative muscle imbalance was performed in 76 eyes of 69 patients undergoing SBP. Measureable limitation of ductions occurred in 40 (73%) of the 55 eyes for which a full set of duction measurements could be obtained. Among 53 patients without previous retinal surgery in either eye, postoperative deviations were associated with encircling scleral buckles (P = 0.00003), but not with radial scleral buckles (P = 0.6). Significant strabismus occurred in 12 patients (23%), and three required surgery or prism therapy. Candidates for pneumatic retinopexy can usually be treated by a radial scleral buckling procedure, and therefore the risk of postoperative strabismus is low if this technique is selected. PMID- 2587044 TI - Vitreous hemorrhage after closed vitrectomy for proliferative diabetic retinopathy. AB - The authors reviewed the medical records of 191 patients (232 eyes) who underwent closed vitrectomy for complications of diabetic retinopathy to evaluate the clinical picture of postvitrectomy hemorrhage (PVH). One hundred thirty-nine eyes (59.9%) had at least one episode of PVH (average, 1.5 per eye) that was variable in onset, not associated with a known cause in four fifths, with no noted source in two thirds, and severe in three fourths of the cases. Using logistic regression statistical analyses, the factors significantly associated with decreased incidence of PVH include older age of patient (P = 0.0004), long duration of surgery (P = 0.0002), and poor preoperative vision (P = 0.05). Of the 139 eyes with PVH, 65 (47%) had spontaneous clearing in an average of 11.3 weeks, 53 (38%) required repeat surgery, and 21 (15%) were inoperable, lost to follow up, or refused reoperation. Postvitrectomy hemorrhage did not significantly influence the final visual outcome. PMID- 2587045 TI - The Wisconsin epidemiologic study of diabetic retinopathy. XI. The incidence of macular edema. AB - As part of a population-based study of diabetes mellitus, the 4-year incidence of macular edema and its relationship to various risk factors was examined in a group of younger onset insulin-taking persons (n = 610) and older onset persons (n = 652). The presence of macular edema at the baseline and follow-up examinations was determined from gradings of stereoscopic fundus photographs. The overall incidence of macular edema in the younger onset group was 8.2% (50/610); in the group of older onset persons using insulin, 8.4% (23/273) and in the group of those not using insulin, 2.9% (11/379). The incidence of macular edema was associated with higher level of glycosylated hemoglobin, longer duration of diabetes, and more severe retinopathy at the baseline examination in both younger and older onset groups. These data provide accurate population-based estimates of incidence of macular edema, and suggest that the level of glycemia is a significant risk factor for the development of macular edema. PMID- 2587046 TI - Importance of the vitreous in young diabetics with macular edema. AB - The authors assessed retrospectively the clinical records of 80 patients (137 eyes) with diabetic retinopathy who were 50 years of age or younger and who had undergone a vitreous examination. The group comprised 53 patients (91 eyes) with macular edema and 27 patients (46 eyes) without macular edema. Vitreous studies using the El Bayadi-Kajiura lens determined whether the posterior vitreous was attached to the retina in the macula. Forty (42.1%) of 91 eyes in the edema group and none (0%) of the 46 eyes in the nonedema group had a detached posterior vitreous. This difference was statistically significant, indicating that young diabetic patients with macular edema have a significantly higher rate of posterior vitreous detachment than those without macular edema. PMID- 2587048 TI - Early retinal adhesion from laser photocoagulation. AB - Histopathologic examination of eight cynomolgus monkey eyes and one human eye revealed that both argon and krypton laser photocoagulation cause adhesion between the neurosensory retina and the retinal pigment epithelium (RPE) within 24 hours of treatment. The neurosensory retina remained attached at the sites of laser burns despite surrounding retinal detachment in untreated areas. This early adhesion with the laser is useful for the treatment of eyes in which the retina has been recently reattached such as at the end of a vitrectomy for a retinal detachment with proliferative vitreoretinopathy (PVR) or after a pneumatic retinopexy. It is also useful for the treatment of retinal breaks without detachment. PMID- 2587047 TI - Retinal blood flow regulation and the clinical response to panretinal photocoagulation in proliferative diabetic retinopathy. AB - Bidirectional laser Doppler velocimetry and monochromatic fundus photography were used to investigate retinal hemodynamics before and after panretinal photocoagulation (PRP) in 25 eyes of 23 diabetic patients with proliferative retinopathy. After PRP, there was a significant decrease in retinal volumetric blood flow rate and an increase in the retinal vascular regulatory response to hyperoxia (R). A significant association was found between the presence or absence of regression of neovascularization and the increase or decrease in R after PRP. Eyes that showed regression of neovascularization had significantly larger average R after PRP than eyes that did not show regression. Lack of improvement in R after PRP may be related to the presence of remaining ischemia or hypoxia in eyes that continue to show proliferation after PRP. PMID- 2587049 TI - Severe retinal vaso-occlusive disease secondary to procainamide-induced lupus. AB - Systemic lupus erythematosus (SLE) is known to cause various forms of ocular problems, including severe retinal vaso-occlusive disease. Procainamide is one of many drugs that may cause a lupus-like syndrome which resembles SLE but can be distinguished through clinical features and laboratory studies. Presented is a patient with severe vaso-occlusive retinopathy on high-dose procainamide therapy. Associated clinical, laboratory, and pathologic findings suggest the diagnosis of drug-induced lupus and exclude other vasculitic or inflammatory etiologies. This represents the first documented case of retinal disease attributed to procainamide-induced lupus. PMID- 2587050 TI - Atrophic macular degeneration. Rate of spread of geographic atrophy and visual loss. AB - The authors studied 50 eyes with atrophic (dry) macular degeneration (geographic atrophy of age-related macular degeneration [GAMD], in 50 consecutive patients for 2 to 6 years (average, 3.4 years). There were 35 women and 15 men ranging in age from 60 to 89 years (average, 73 years). The areas of atrophy tended to follow the disappearance or flattening of soft drusen, pigment epithelial detachment, or reticular mottling of the retinal pigment epithelium. The atrophic areas were multifocal in 20 of the 50 eyes. Atrophy of the retinal pigment epithelium was followed by atrophy of the choriocapillaris. The atrophic areas tended to expand (average rate in one direction, 139 microns per year) and cause gradual loss of central visual acuity. The rate of significant visual loss (from 20/50 or better to 20/100 or worse) was 8% of eyes per year. There was a tendency toward resistance of the spread of atrophy into the fovea. The atrophy tended to expand faster in patients under age 75 and slower in patients aged 75 and over. Subretinal neovascularization developed in ten of the 50 eyes. PMID- 2587051 TI - Loss of human photoreceptor sensitivity associated with chronic exposure to ultraviolet radiation. AB - The crystalline lens of the human eye absorbs most of the incident ultraviolet radiation (UVR), but when the lens is removed, this radiation can reach the photoreceptors. The consequences of UVR exposure on cone receptor sensitivity were determined from psychophysical measurements in patients who had undergone bilateral cataract extraction and implantation of intraocular lenses (IOLs). The IOL implanted in one eye contained chromophores that absorb incident UVR, whereas that implanted in the other eye transmitted UVR. Five years of exposure to ambient UVR was associated with a selective loss in sensitivity of the short-wave cone photoreceptors. These results are consistent with the hypothesis that chronic exposure to UVR may damage the human retina. PMID- 2587052 TI - Endoretinal biopsy in immunosuppressed and healthy patients with retinitis. Indications, utility, and techniques. AB - Endoretinal biopsies were taken using pars plana vitrectomy techniques in 13 eyes with inflammatory or infectious retinitis complicated by retinal detachment (RD). The surgical technique has evolved over a 4-year period. The authors review the surgical technique including techniques of removal of the vitreous, appropriate hemostasis, selection of the biopsy site, and atraumatic removal of the tissue from the vitreous cavity. Careful processing of the material for histopathology, immunopathology, and electron microscopy is necessary and has provided useful information in patient diagnosis and management. The authors have used the technique in cases of rhegmatogenous RD complicating presumed viral retinitis. The technique has proven to be useful in confirming the clinical diagnosis and is relatively safe when used in selected cases. PMID- 2587053 TI - Managing cataracts in patients with uveitis. PMID- 2587054 TI - Eyelid retraction in Graves' eye disease. PMID- 2587055 TI - [Clinical, x-ray and arthroscopic parallels in initial stages of deforming arthrosis of the knee joint]. AB - The study is based on the results of a clinical, roentgenologic and arthroscopic examination of 166 patients at the early stages of development of deforming arthrosis of the knee joint. The peculiarities of the early clinical, roentgenologic and arthroscopic symptoms and their relationship with the causative factors of the development of the disease have been investigated. The parallels between clinical and roentgenologic manifestations have been determined with regard to the degree of the degree of the degenerative and dystrophic changes in the articular cartilage, which is of major importance for the early diagnosis and the development of rational treatment of this pathologic condition. PMID- 2587056 TI - [Our experience in the treatment of deformations of the knee joint in arthrogryposis]. AB - During the past 12 years the authors have observed 96 children with deformations of the knee joints associated with arthrogryposis. 54 children were given surgical treatment. The deformations of the knee joints were eliminated differently with regard to the severity of the deformations. In 27 children with correct correlations between the femur and the tibia the deformations of the knee joints (39) were corrected by the method of compression and distraction. In severe cases the contractures of the knee joints (30) with impaired correlations of the bones in the children over 5-6 years of age the compression and distraction method was combined with the open reduction of the dislocation of the bones of the crus and lavsan plasty of the retracted musculus rectus femori and the ligaments of the articulation. The long-term results of the surgical treatment of arthrogryposis deformations of the knee joints (1 to 12 years) were studied in 48 children. As the result of these surgical interventions 45 children began to move on their own. PMID- 2587057 TI - [Reconstructive surgery in post-traumatic contractures of the knee joint]. AB - 214 patients with posttraumatic contractures of the knee joint were treated at the Leningrad Research Institute of Orthopaedics and Traumatology in 1970-1985. In 67 patients the Thompson-Kaplan operation was performed. Since 1980 an operation worked out at the Institute has been made in 194 patients. Their treatment results were much better, especially in the patients with the most severe contractures of the knee joint which developed after diaphyseal and intraarticular fractures of the femur as well as after preceding osteomyelitis or purulent gonitis. PMID- 2587058 TI - [Ligamento-periostosis of the attachment of the patellar ligament]. AB - The analysis of 1140 observations of ligamento-periostosis of the apex of the patella (the proximal attachment of its proper ligament) revealed that it was rather frequently present (3.1%) in the latent form during the prophylactic examinations of sportsmen, which constituted an important part (7.6%) in the structure of the diseases of the locomotor system. It was confirmed that the disease depended on the intensity of the loads and on the age of the patients. Early (at the preclinical stage) treatment allows to reduce the transition of the latent course of the disease into its clinical forms down to 6%. The administration of a complex treatment with novocaine electrophoresis and vitamin R12, drug blocks of the pathologic foci at the site of the attachment of the ligament and differential correction of the static and dynamic loads provide for steady healing without recurrences and relapses of the disease in 89% of the patients. PMID- 2587059 TI - [Pathogenesis of degenerative-dystrophic changes in the hip joint]. AB - The authors have examined 43 children by the method of radiotropic angiography, 27 of whom had various diseases of the hip joint area. The blood flow in the iliac vessels and the regional blood flow in the area of the affected vessels was studied before and after the operation making use of an osteotropic radiopharmacological drug (RPD) 99mT-phosphon. Independent of the character of the degenerative and dystrophic process in the hip joints there was a reduction in the intensity of the blood flow on the affected side reaching 15-30%, which was more expressed at stage 111 of coxarthrosis with no considerable changes after the operation. In the control group this difference was +/- 5%. The regional blood flow (RBF) in the area of the operation was reduced down to 37% before the operation and increased by 17-35% 6-8 months after the operation with the exception of the cases of dystrophic lesions of the neck when no increase in the RBF was observed. The authors come to the conclusion about a relationship between the deviation from the normal conditions in the intensity of the blood flow and the degenerative and dystrophic processes in the hip joints. PMID- 2587060 TI - [Pathways of intra-articular transport of cholesterol esters]. AB - The authors have carried out an experimental study of an insufficiently explored problem of the diffusion capacity of the ethers of cholesterol through the skin and the possibility of their intra-articular transport with cholesterol ether of the oleic acid marked 1,2(3)H taken as an example. It has been established that the drug penetrates through the skin and appears in the joint cavity. The results expand our ideas of the biological role of lipids and present the arguments in favour of the hypothesis of their participation in the mechanism of reduction of intra-articular friction. PMID- 2587062 TI - [Formation of the hip joint in patients with cerebral paralysis]. PMID- 2587061 TI - [Scintigraphy in postoperative coxarthrosis in children and adolescents]. AB - To optimize the therapeutic tactics in 21 patients aged 7 to 15 with postoperative coxarthrosis the authors have studied some characteristics of the regional blood flow and the metabolic processes in the area of the hip joints. The results that have been obtained point at the incentive of the regional blood flow and the metabolic processes in this disease. The changes in the processes under study during the postoperative period have been demonstrated. PMID- 2587063 TI - [Methods of functional management of patients after arthroplasty of the hip]. AB - The authors present their methods of working out the movements in the first days after the arthroplasty of the hip joint performed according to A. C. No. 1058493 (1982). The peculiarities of the management of the patients with bilateral pathology with a steady flexion and adduction contracture or ankylosis with a faulty posture of the extremity in the opposite unoperated joint have been pointed out. PMID- 2587065 TI - [Pathological reconstruction of the tibia after radiotherapy]. AB - In 6 patients with sarcomas of the bones of the crus at different periods following radiotherapy the authors have revealed pathologic reconstruction of the structure of the tibia. A roentgenologic picture of the changes in the course of the dynamic observation of the patients and their treatment is presented. It has been demonstrated that the conservative treatment effective. PMID- 2587064 TI - [Clinico-radiologic evaluation of deformation of the foot and lower limb in congenital clubfoot]. AB - In a typical form of congenital club foot there is a complex primary and secondary post-loading deformation both of the feet and of all the bones of the lower extremity which by all means should be taken into consideration when correction with apparatuses of perosseous external fixation is carried out for the complete elimination of the congenital malformation and the prevention of a recurrent deformation. PMID- 2587066 TI - [Results of Krasovitov's dermatoplasty]. AB - The authors analyse their results of reimplantation of skin after Krasovitov in 34 patients. In 23 cases there were good or satisfactory results and in 10 cases where there were deviations from this technique the results were not satisfactory. The most frequent mistake was leaving of the scalped skin on the "feeding" pedicle. In scalped wounds associated with bone fractures the authors used perosseous osteosynthesis which stabilized the fracture and did not cause difficulties in taking care of the reimplanted skin. To improve the results of the operations drugs influencing the rheologic properties of the blood and the vegetative innervation were administered. PMID- 2587067 TI - [A method of surgical treatment of habitual dislocation of the patella]. PMID- 2587068 TI - [Lateral pelvic holder]. PMID- 2587069 TI - [Repositioning ring for compression-distraction apparatus]. PMID- 2587070 TI - [Apparatus for repositioning the posterior border of the tibia]. PMID- 2587071 TI - [A stand for training students]. PMID- 2587072 TI - [A device for an x-ray examination of the hip joints]. PMID- 2587073 TI - [Injuries of the menisci in patients with deforming gonarthrosis]. AB - The authors present their observations concerning the difficulties in the diagnosis of the injuries of the menisci of the knee joint associated with deforming arthrosis which have quite a number of similar clinical signs with injuries of the menisci. The importance of an arthroscopic study of the meniscus of the knee joint is demonstrated for revealing the lesion as well as a possibility of solution to the problem of partial meniscectomy. The expediency of such tactics is confirmed by the results of the treatment of 28 patients, in 10 of whom lesions of the inner menisci were revealed and partial meniscectomies were performed. The remaining 18 patients were given sanation of the joint cavity. The results of the treatment with a follow-up period up to 5 years were evaluated as good. PMID- 2587074 TI - [Economic aspects of the treatment of patients with diaphyseal fractures of the humerus]. PMID- 2587075 TI - [Rendering aid on board to seamen with injuries of the locomotor system]. PMID- 2587076 TI - [Treatment of instability of the knee joint]. AB - The authors present a study of problems of the surgical treatment of acute and chronic instabilities of the knee joint. In cases of recent injuries 32 operations of restoration of the cruciate ligaments and the bursal and ligamentous apparatus were made: in most cases the long-term results were good. The authors believe that timely and adequate treatment of the patients during the acute stage of the disease will allow to bring the problem of the treatment of chronic instability of the knee joint in most patients closer to its practical solution. In primarily anterior and posterior chronic instability associated with a light degree of lateral instability an operation after Augustino is advised, particularly as modified by the authors, as an independent operation or as one of the elements in complex reconstructive operations in the multiplane forms of instability of the knee joint. A detailed description of the surgical technique is given. PMID- 2587077 TI - Our vasoconstrictive lifestyle. PMID- 2587078 TI - Physicians understand pro bono. PMID- 2587079 TI - The psychiatric short procedure. PMID- 2587080 TI - Geriatric medicine 1989--where are we now? PMID- 2587081 TI - It's going, going ... not quite gone. PMID- 2587082 TI - Small deaths in a trial. PMID- 2587083 TI - HIV infection in relation to homosexual behavior. PMID- 2587084 TI - Pennsylvania pro contract open for bids. PMID- 2587085 TI - Recent advances in pediatric otolaryngology. PMID- 2587087 TI - A unique setting for pediatrics: the Hole in the Wall Gang Camp. AB - More than a camp for special children, actor Paul Newman's Hole in the Wall Gang Camp provides a therapeutic and recreational experience for children with cancer and blood diseases. The editor of Pediatric Nursing describes the camp, the idea, and how the concept was operationalized. PMID- 2587086 TI - The relationship between nasal obstruction and craniofacial growth. AB - The relationship between nasal obstruction and craniofacial growth is unclear. The literature indicates that upper-airway compromise produces chronic mouth breathing, especially in the dolichocephalic (narrow-faced) child. It has been shown that a greater tendency exists toward the skeletal pattern associated with long face syndrome in dolichocephalic head types. Therefore, it becomes difficult to assess whether the long face syndrome is a cause or an effect of increased nasal airway resistance. Nevertheless, animal studies have demonstrated the development of typical craniofacial anomalies in experimentally induced nasal obstruction. Some of these changes are also noted to be reversed by removing the nasal obstruction. Although much of the concern for nasal obstruction and abnormal dentofacial growth has centered around adenotonsillar hypertrophy, other causes for nasal obstruction should be sought. Allergic rhinitis and choanal atresia also should be considered. Longitudinal data are lacking to support conclusively abnormal dentofacial growth as an indication for surgical intervention. Available literature would suggest, however, that relief of nasal obstruction should be attempted in an effort to establish a patent airway and decrease the possibility of abnormal craniofacial development. The more information we gain about nasal obstruction and abnormal dentofacial development, the greater our diagnostic ability becomes. We can now incorporate information from a thorough nasal-oral examination with rhinomanometry and cephalometrics to provide a rational treatment plan for these children. Future directions should investigate genetic influences on craniofacial morphology and growth. PMID- 2587088 TI - Respiratory syncytial virus: a nursing perspective. AB - Respiratory syncytial virus (RSV), a common winter illness, is most devastating in infants with underlying pulmonary and cardiovascular disease. Ribavirin aerosol is an effective treatment when used with appropriate nursing management. PMID- 2587089 TI - Factors related to spontaneous endotracheal extubation in the neonate. AB - Circumstances accompanying spontaneous endotracheal extubation (SE) in neonates reveal a trend that very low birth weight infants who are ventilated for several weeks are most prone to this complication. PMID- 2587090 TI - Using sign language with tracheotomized infants and children. AB - Children's ability to communicate with others is important for cognitive development. However, the number of infants and young children deprived of vocalization (aphonia) is increasing in the pediatric patient population due to tracheotomy. The Communication Program for Infants and Parents (CPIP) uses sign language as an alternative system to verbal communication. PMID- 2587091 TI - Home care for ventilator-assisted children: predicting family stress. AB - Predictors of family and caregiver stress are identified and used to construct a profile of families at greatest risk of experiencing stress when providing home care for their ventilator-assisted children (VAC). PMID- 2587092 TI - A guide to delegation. AB - Delegation is an essential requirement for effective nursing management. Used properly, delegation can foster growth of workers, alleviate tension, and contribute to a smoother working environment. This article outlines the four steps of delegation. PMID- 2587093 TI - Pediatric management problems. Anorexia nervosa causing amenorrhea. PMID- 2587094 TI - Verifying endotracheal tube placement with the TRACH ++ MATE intubation system. AB - Determining the location of the endotracheal tube in critically ill infants and children often creates uncertainty for critical care nurses. A newly developed endotracheal tube system (TRACH MATE) improves confidence in assessing endotracheal tube placement when used appropriately. PMID- 2587095 TI - Anatomy of a test question. PMID- 2587096 TI - Making adolescent space in a pediatric office. AB - The pediatric office nurse is in a position to act as a change agent and advocate to provide better care for the adolescent population. PMID- 2587097 TI - Consent for minors. AB - Consent for minors is an issue health care institutions must deal with frequently. Development of a mature minors policy is a worthwhile ethical and legal undertaking for every institution. PMID- 2587099 TI - What's new with sunscreens? Choices--choices--choices. PMID- 2587098 TI - Comparison of survivors and nonsurvivors in pediatric intensive care. AB - PURPOSE: To identify characteristics of survivors and nonsurvivors among critically ill children admitted to a pediatric intensive care unit. METHOD: A retrospective chart review of 91 children (64 survivors and 27 nonsurvivors) compared age, gender, diagnostic category, and number of days in the ICU. Data were analyzed by Fisher's Exact Test and ANOVA. RESULTS: There were no significant differences among groups. CONCLUSIONS: Data contribute to the development and testing of predictive models for decision-making in pediatric intensive care. PMID- 2587100 TI - Clarification on AAP statements. PMID- 2587101 TI - Is theory application merely an intellectual exercise? PMID- 2587102 TI - Assessing parents as health educators. AB - Parental health knowledge and beliefs are critical determinants in decisions concerning health care matters of children. This article describes a data collection instrument based on Orem's Self-Care Theory that can predict the potential for health education in the home. PMID- 2587103 TI - A clinical application of Watson's theory. AB - Watson theorized nursing as a human science. Ten carative factors are identified as the principles in nursing. Application of Watson's Theory to nursing practice in a pediatric setting is explored. PMID- 2587104 TI - Orem's theory applied to pediatric residential treatment. AB - Nurses working in multidisciplinary pediatric residential treatment facilities must maintain a clarity of domain. The Orem Self-Care Model is evaluated for the use in settings of this kind and shown to be both appropriate and adaptable. PMID- 2587105 TI - Preop use of Golytely in pediatrics. AB - Polyethylene glycol-electrolyte lavage solution (PEG-ELS) is a whole gut lavage solution designed to cleanse the gastrointestinal tract prior to bowel surgery or endoscopy. This method relies on pediatric nurses safely administering a large volume of PEG-ELS, marketed as Golytely, to produce the flushing effect without significant absorption of the Golytely. PMID- 2587106 TI - Pediatric management problems. Neonatal abstinence syndrome. PMID- 2587107 TI - The implications of certification. PMID- 2587108 TI - Professional writing and personal style. AB - Within our profession we need to dispel the mystique surrounding the notion of writing for publication. Anyone interested in writing can do so with self understanding, proper information, and preparation. PMID- 2587109 TI - Implications of certification--legal considerations. AB - With certification of specialty nurses here to stay, nurses and certifying organizations must understand several legal issues associated with the process. PMID- 2587110 TI - Response to letter on i.v. infusions of gentamicin and ampicillin. PMID- 2587111 TI - Teenagers and the mothering experience. AB - PURPOSE: To determine the relationship between maternal age, perceived social support, and home environment to mother-child interaction. METHOD: Thirty-three adolescent mother-child pairs and 33 older mother-child pairs were randomly selected from a pool of 63 adolescent mothers and 111 older mothers. The Nursing Child Assessment Feeding Scale (NCAFS), the Personal Resource Questionnaire (PRQ), and the Home Observation for Measurement of the Environment (HOME) were completed during a scheduled home visit. One way ANOVA and Multiple Correlation were used to analyze the data. RESULTS: Mother's sensitivity to cues and social emotional growth-fostering from the NCAFS favored older mothers. Avoidance of restriction and punishment from the HOME favored older mothers. There was a significant relationship between perceived social support and mother-child interaction for both groups. CONCLUSIONS: Maternal behavior was related to mother's age. A mother's perception of the adequacy of her social support resources may be a critical factor in how she interacts with her child. PMID- 2587112 TI - Preparation for neonatal emergencies: a neonatal emergency medication sheet. AB - Safe and timely administration of emergency medications and infusions is crucial when caring for critically ill neonates. A neonatal emergency medication sheet can enhance preparation, calculation, and administration of medications during emergency situations in neonatal intensive care units (NICUs). PMID- 2587113 TI - Developing a basic management course for assistant head nurses. AB - Assistant head nurses (AHNs) can be an integral part of a management team. This article details a basic program that helps AHNs develop strong management skills and upgrades the quality of nursing departments. PMID- 2587114 TI - Discharge planning for the breastfeeding dyad. AB - The increase in early hospital dismissal of postpartum mothers has dramatically decreased the amount of time available for teaching of breastfeeding. PMID- 2587116 TI - Influence of thromboxane A2 receptor antagonism on pulmonary vasoconstrictor responses. AB - Thromboxane A2 (TxA2) is an arachidonic acid metabolite which causes severe pulmonary vasoconstriction (PV) and may mediate the PV produced by platelet activating factor (PAF-acether) and leukotriene D4 (LTD4). To determine the role of TxA2 receptors on PAF-acether, LTD4, and hypoxia-induced PV, we administered PAF-acether 0.1 nmol/kg, the TxA2 analog U-46619 0.2 micrograms/kg/min, LTD4 3.0 micrograms/kg, or acute hypoxia (FiO2 = 0.12 for 3 min) before and during the infusion of the selective TxA2 receptor blocker SQ 29,548 50 micrograms/kg/min or vehicle into 27 open-chest, anesthetized newborn piglets, measuring pulmonary and systemic arterial pressures, cardiac index, and right and left ventricular pressures and dimensions. Mean pulmonary arterial pressure rose and cardiac index fell in response to PAF-acether (14 +/- 1 to 32 +/- 2 mm Hg and 91 +/- 5 to 15 +/ 5 mL/kg/min, both p less than 0.01), U-46619 (11 +/- 1 to 28 +/- 2 mm Hg and 93 +/- 10 to 36 +/- 9 mL/kg/min, both p less than 0.01), and LTD4 (13 +/- 3 to 22 +/ 2 mm Hg and 85 +/- 12 to 29 +/- 9 mL/kg/min, both p less than 0.05). Acute hypoxia increased PAP (12 +/- 1 to 26 +/- 2 mm Hg, p less than 0.01) but did not alter cardiac index. Infusion of SQ 29,548 prevented PAF-acether and U-46619 induced increases in pulmonary arterial pressure (13 +/- 1 to 14 +/- 1 mm Hg and 12 +/- 1 to 12 +/- 1 mm Hg) and decreases in cardiac index (70 +/- 4 to 70 +/- 3 mL/kg/min and 94 +/- 14 to 92 +/- 12 mL/kg/min) but failed to alter the response to LTD4 or hypoxia. Vehicle had no effect. We conclude that TxA2 receptors are not involved in LTD4 or hypoxia-induced PV but play an important role in the PV produced by PAF-acether and U-46619. PMID- 2587115 TI - Ontogeny of surfactant apoproteins in the rat. AB - Content of the 26-38-kD surfactant apoprotein (SP-A) was determined in lung homogenates from fetal (17-21 d gestation), postnatal (1-28 d of life), and adult male and female rats by a double sandwich ELISA. Expression of mRNA for SP-A as well as the hydrophobic apoproteins, SP-B and SP-C, were also determined in lung homogenates from fetal and adult rats of both sexes by Northern blot analysis. SP A was undetectable in fetal lungs on d 17 (day of birth = d 22) and barely detectable on d 18. On d 19 there was a 3- to 4-fold increase in SP-A content above d 18 levels. Between d 19 and 21 SP-A content significantly increased another 6- to 9-fold. SP-A content on the day of birth was not significantly different from that seen on gestational d 21. SP-A content decreased 35-40% between the day of birth and postnatal d 7. After the second postnatal week SP-A content gradually increased, reaching adult levels after d 28. No sex differences in SP-A content were observed during fetal or postnatal lung maturation. SP-A mRNA was first detected in fetal lungs on d 18 and increased in relative abundance until d 21, but remained below adult levels. Developmental changes in fetal lung SP-A content closely paralleled changes in fetal expression of SP-A mRNA. SP-B mRNA was also first detected on d 18, then increased in relative abundance to adult levels by d 20. SP-C mRNA was clearly detectable on d 17, then increased in relative abundance to adult levels by d 20-21. Unlike surfactant phospholipids, there are no apparent sex differences in the expression of any of the surfactant apoproteins during late gestation. The differences observed during fetal lung maturation in the time of onset and changes in relative abundance among the three apoprotein mRNA imply that their genes may be differentially regulated in the developing rat lung. PMID- 2587117 TI - Response to low cardiac output: developmental differences in metabolism during oxygen deficit and recovery in lambs. AB - When cardiac output is critically lowered, whole body O2 consumption decreases and an O2 deficit accumulates. With restoration of cardiac output, an excess O2 consumption is expected in order to "repay" some or all of the O2 deficit. We tested the hypothesis that young lambs, with higher resting O2 consumption, cardiac output and growth rates than older lambs, would repay less of their O2 deficit because they have a higher proportion of nonessential metabolism. We reduced cardiac output acutely by inflating a Foley catheter in the right atrium of spontaneously breathing, sedated lambs at ages 2 (n = 5) and 8 (n = 5) wk. Each lamb was studied with low cardiac output periods of 30 and 60 min on different days. Aortic and pulmonary artery blood pressures, gases, and O2 saturations, venous Hb, and arterial lactate concentrations were measured every 10 min during baseline, low output, and 60 min of recovery. Oxygen consumption was monitored continuously. Oxygen deficit and excess O2 of recovery were calculated from the time integral of the difference between O2 consumption at baseline and during the respective study period. The average percent decreases in cardiac output (66.4 and 64.6%) and O2 consumption (38.1 and 35.1%) were similar in the 2- and 8-wk groups, respectively. There was no consistent relation between O2 deficit and O2 repayment in either age group. However, on average the 2-wk group repaid a significantly lower percentage (3 +/- 16%, mean +/- SEM) than 8-wk olds (76 +/- 29%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2587118 TI - Heart rate variability analysis in full-term infants: spectral indices for study of neonatal cardiorespiratory control. AB - The heart rate and respirations of twenty healthy full-term infants between 30 and 60 h postnatal age were studied during quiet sleep with the objective of defining spectral indices which represent normal neonatal heart rate variability (HRV) characteristics. Total HRV power and the distribution of power across different frequency bands varied considerably among infants. Cluster analysis on the measured variables indicated that the population divided into two groups that represented significantly different patterns of HRV behavior. In one group (11 subjects), infants had lower breathing rates and HRV power in a band about the respiration frequency [respiratory sinus arrhythmia (RSA) band] was more than 20% of the total power (TP). Additionally, the ratio of low frequency band power to RSA band power was less than 4. The other group of neonates (nine subjects) had relatively higher breathing rates, RSA power less than 20% of total power, and low frequency to RSA power ratio greater than 4. Regression analysis of low frequency versus TP and RSA versus TP graphs gave strong support to the hypothesis that there were indeed two distinct patterns of HRV behavior. Separation of apparently normal neonates into two groups may be attributed partially to differences in respiratory rates and breathing patterns. However, it is possible that differences in the balance between sympathetic and parasympathetic nervous system control, perhaps related to autonomic maturation, also contribute to group separation. The indices developed from HRV spectral analysis in this investigation may be of value in the study of cardiorespiratory control in neonates. PMID- 2587119 TI - The effect of aminophylline on diaphragm blood flow in the piglet. AB - The effect of aminophylline on diaphragmatic blood flow was investigated in two groups of newborn piglets. Six animals were studied during spontaneous breathing and seven additional animals were paralyzed and ventilated to assess the effect of aminophylline on blood flow to the nonworking diaphragm. Arterial blood gases and pH, cardiac output, and diaphragmatic blood flow were measured before and 20 min after infusion of 20 mg/kg aminophylline. Blood theophylline concentrations averaged 117 mumols/L (21 micrograms/mL) in both groups of animals. Heart rate increased significantly in all animals. Cardiac output increased significantly only in spontaneously breathing animals. Aminophylline had no effect on blood flow to the costal or crural portions of the diaphragm in either the paralyzed or spontaneously breathing animals. PMID- 2587120 TI - Effect of low dose dopamine on hemodynamic and renal function in children. AB - The purpose of the study was to investigate the effect of low doses of dopamine in children. Fourteen cases were studied after open heart surgery. Cardiac output and renal parameters were determined under baseline conditions and under continuous infusion of dopamine 2.5 and 5 micrograms/kg/min. During the control period cardiac index was 2.62 +/- 0.19 L/min/m2, renal plasma flow was decreased at 269 +/- 41 mL/min/1.73 m2, GFR was 86.6 +/- 9.2 mL/min/1.73 m2, and filtration fraction was elevated at 37.1 +/- 1.9%. Plasma concentration of aldosterone correlated with the filtration fraction. At 5 micrograms/kg/min dopamine increased significantly cardiac output, renal plasma flow, and to a lesser extent GFR, thus decreasing the filtration fraction. At 2.5 micrograms/kg/min dopamine, increased renal plasma flow only in patients older than 5 y and had no effect on the other parameters. The increase of cardiac output in response to dopamine was abolished by propranolol pretreatment. By contrast, the hemodynamic renal response to dopamine was not altered by beta-blockade. These results indicate that 5 micrograms/kg/min of dopamine could prevent renal failure after open heart surgery in children by increasing renal blood flow and attenuating renal compensatory mechanisms. PMID- 2587121 TI - The effects of exogenous rat growth hormone therapy on growth of uremic rats fed an 8% protein diet. AB - Although the mechanisms underlying the inhibitory effects of chronic renal insufficiency on growth are poorly understood, large doses of growth hormone (GH) have been used to improve growth. The present study examines the effects of rat GH and a reduced (8%) protein diet on 75% nephrectomized weanling rats by measuring changes in growth parameters, food utilization, serum albumin concentration, and muscle water content. Significantly greater improvement in growth was found in the GH-treated uremic rats compared with the uremic controls. The mean percent change in wt, length (nose to tail tip), and cranial biparietal diameter was significantly increased in the GH-treated uremic rats, compared with the uremic controls, but foot length and femur length showed only moderate improvement. Food utilization efficiency and serum albumin concentration were significantly higher in GH-treated uremic rats compared with uremic controls, achieving levels that were not different from sham-operated rats. Muscle water content was not significantly different between GH-treated uremic rats, uremic controls, and sham-operated rats. Thus, rat GH treatment administered at an early age in mild renal insufficiency significantly improved overall growth, food efficiency, and serum albumin concentrations, despite a low protein diet, suggesting that further evaluation of this form of therapy for growth failure of uremia is warranted. PMID- 2587122 TI - Regional cerebral glucose utilization in the immature rat: effect of hypoxia ischemia. AB - The 2-deoxy-[14C]-glucose (2-DG) method of Sokoloff was used to assess regional cerebral glucose utilization (CGU) in the immature rat. The 7-d postnatal rats received 2.5 muCi 2-DG subcutaneously, after which blood was collected for measurement of plasma glucose and 2-DG activity at intervals up to 90 min. The brains of the 90-min rat pups either were frozen for analysis of glucose concentration and chromatographic separation of 2-DG and 2-DG-6-phosphate or for [14C]-autoradiography. A lumped constant of 0.55 was calculated from plasma and brain glucose levels of 6.4 and 1.62 mmol/L.kg, respectively. Of the [14C] activity in brain, 75.6% was in the 2-DG-6-phosphate fraction; this percent was substituted for K1*, K2*, and K3* in the Sokoloff equation. Cerebral hemispheric CGU (n = 6) averaged 11.4 +/- 1.5 mumol/100 g/min, 1/10 the value of adult rat brain. Rates in 16 brain structures (n = 10) ranged from 7.8 (frontal white matter) to 16.9 (cerebellum) mumol/100 g/min. During hypoxia-ischemia (unilateral common carotid artery ligation combined with exposure to 8% oxygen), the lumped constant increased to 1.04, and 99% of 2-DG was converted to 2-DG-6-phosphate. Increases in CGU occurred in all eight structures of the cerebral hemisphere ipsilateral to the carotid artery occlusion (n = 9), ranging from 287% (frontal white matter) to 445% (striatum) of control values (p less than 0.05). Relatively comparable elevations in CGU (234-435% of control) occurred in the contralateral cerebral hemisphere, which were not significantly different from those of the ipsilateral hemisphere.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2587123 TI - The role of oxygen free radicals in postasphyxia cerebral hypoperfusion in newborn lambs. AB - Previous work in a neonatal lamb model has demonstrated abnormalities in cerebral blood flow (CBF) and oxygen consumption (CMRO2) after asphyxia. Immediately after resuscitation, there was a marked increase in CBF and a significant decrease in CMRO2 compared to control. During the late period after asphyxia (30 min to 4 h), both CBF and CMRO2 were significantly depressed. The same postasphyxia model (n = 16) was used to examine the hypothesis that generation of oxygen free radicals during cerebral reperfusion may be involved in the genesis of late postasphyxia hypoperfusion and depressed CMRO2. Before asphyxia, the animals were pretreated with either inactivated (n = 8) or active (n = 8) polyethylene glycol superoxide dismutase, 5000 U/kg, and polyethylene glycol catalase, 100 000 U/kg. CBF (radioactive microspheres) and arterial and venous (superior sagittal sinus) blood gases and O2 contents were measured during control, and at 5 min, 1 h, 2 h, and 4 h postasphyxia (PA). In the active enzyme group, 5 min postasphyxia CBF was significantly increased compared to control: 211.5 +/- 28.0 versus 78.6 +/- 11.4 ml.100 g-1.min-1, +/- SEM, p less than 0.005. At 1 h (82.9 +/- 17.6), 2 h (62.3 +/- 5.5), and 4 h (78.9 +/- 12.2) PA, CBF did not differ significantly from control. More importantly, CMRO2 did not differ from control at any time PA. In the inactive enzyme group, both CBF and CMRO2 were depressed at 1, 2 and 4 h PA. These findings are consistent with a conclusion that damage by oxygen free radicals during postasphyxia cerebral reperfusion is important to the genesis of late PA blood flow and O2 metabolism abnormalities. To the extent that depressions in CBF and CMRO2 result in ongoing brain injury, agents that ameliorate these abnormalities may improve neurologic outcome. PMID- 2587124 TI - Perinatal development of heart, kidney, and liver mitochondrial antioxidant defense. AB - Development of the mitochondrial antioxidant defense system was studied to assess its potential role in the newborn mammal's tolerance to oxidative challenge and to gain insight into the fetal adaptation to a relatively hyperoxic adult environment. Isolated heart, kidney, and liver mitochondria from fetal, newborn, and adult guinea pigs were used. In situ function of the antioxidant enzymes was estimated in mitochondrial suspensions after the addition to selenite or tert butyl hydroperoxide by determining NAD(P)H oxidation rates spectrophotometrically at 340-375 nm. Kidney and liver mitochondria from newborn animals were less susceptible to selenite and tert-butyl hydroperoxide-induced NAD(P)H oxidation. The pattern of change, however, varied widely with tissue type. Kidney mitochondria displayed the largest change with a 3- to 4-fold increase in rate from the fetal to adult period. NAD(P)H oxidation rates in intact mitochondria did not correlate consistently with glutathione reductase and peroxidase activities in sonicated mitochondria suggesting in situ regulation by other endogenous factors. Immediately after birth, mitochondrial glutathione reductase and peroxidase activities dropped 38-50% and 50-70%, respectively, in all tissues studied. Total glutathione content of heart and liver mitochondria did not change with age. Adult kidney mitochondrial glutathione, however, declined to 24% of fetal values. Mitochondrial superoxide dismutase activity increased 150-300% from the fetal to the adult period in all tissues studied. Perinatal changes in the mitochondrial antioxidant system and their relationship to mitochondrial calcium metabolism are discussed in terms of the newborn's resistance to oxidative stress. PMID- 2587125 TI - Superoxide dismutase in polymorphonuclear leukocytes of term newborn infants and very low birth weight infants. AB - We investigated the activity and the content of copper and zinc-containing superoxide dismutase (SOD) and superoxide anion (O2-) production in polymorphonuclear leukocytes (PMN) from healthy term newborn infants, very low birth wt infants, and healthy adults. SOD activity in PMN was measured with nitroblue tetrazolium reduction assay on PAGE, and the SOD content in PMN was determined with an ELISA using a monoclonal antibody against human copper and zinc-containing SOD. The activity and the content of SOD in the term neonatal PMN and VLBW-infants' PMN were significantly lower than those in the adults' PMN (term newborn infants, 6.6 +/- 0.6 U/mg protein and 170.4 +/- 16.3 ng/mg protein, n = 10; VLBW infants, 6.8 +/- 0.9 and 173.0 +/- 16.2, n = 6; adults, 10.3 +/- 0.6 and 241.9 +/- 13.3, n = 10; values were expressed as mean +/- SEM). Both the phorbol myristate acetate- and the N-formyl-methionyl-leucyl-phenylalanine induced O2- production rates of VLBW-infants' PMN were significantly higher than those of the term neonatal PMN. The phorbol myristate acetate-induced O2- production rate of the term neonatal PMN was significantly lower than that of the adults' PMN. The phorbol myristate acetate-induced H2O2 production rate of the term neonatal PMN was significantly lower than that of the adults' PMN. The conversion rate from O2- to H2O2 of the neonatal PMN was similar to that of the adults' PMN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2587126 TI - Iron absorption from infant foods. AB - To determine the bioavailability of iron from iron-fortified infant foods, we have determined erythrocyte incorporation of the stable isotope, 58Fe, after feeding the following foods extrinsically labeled with 58Fe: 1) rice cereal with apples and bananas ("cereal-fruit product"), 2) Mead Johnson Enriched Baby Food (MJEBF), a vitamin, mineral, and protein-enriched rice cereal, 3) vegetables and beef ("vegetable-beef product"), 4) grape-juice, and 5) MJEBF. Foods 1-4 were fortified with ferrous sulfate, and food 5 was fortified with ferrous fumarate. Blood was obtained at ages 140, 168, and 196 d of age, and the test meal was fed under standardized conditions at 154 d of age. Erythrocyte incorporation of the 58Fe label was determined from the increase in the mass isotope ratio, 58Fe/57Fe, from the baseline value (at 140 d of age) to the follow-up values. The mass isotope ratio was determined by inductively coupled mass spectrometry. Geometric mean total iron incorporation into erythrocytes from the test meal of MJEBF fortified with ferrous sulfate (food 2) was 0.05 mg, and from the vegetable-beef product test meal (food 3) was 0.08 mg. The low value for MJEBF is presumably explained by the low level of iron fortification. The low value for the vegetable beef product may reflect the presence of inhibitors of iron absorption. Geometric mean erythrocyte incorporations of iron from the test meals with foods 1, 4 and 5 were 0.15, 0.14, and 0.18 mg, respectively. These erythrocyte incorporation values are 20 to 26% of the estimated 0.7 mg requirement for absorbed iron, and therefore seem nutritionally important. PMID- 2587127 TI - Biotinidase deficiency: a cause of subacute necrotizing encephalomyelopathy (Leigh syndrome). Report of a case with lethal outcome. AB - An unusual clinical course of a patient with biotinidase deficiency, causing Leigh syndrome, is reported. Laryngeal stridor was the major presenting symptom followed by progressive neurologic deterioration and death at the age of 21.5 mo. Absence of skin and hair abnormalities as well as of organic aciduria delayed the correct diagnosis. Necropsy revealed subacute necrotizing encephalopathy (Leigh syndrome). Carboxylase activities (propionyl CoA carboxylase, 3-methylcrotonyl CoA carboxylase, pyruvate carboxylase) measured in lymphocytes 1 day before death were decreased to 10% of normal values. Propionyl-CoA carboxylase was shown to be the only stable carboxylase in human postmortem tissue; in our patient it was moderately decreased in postmortem liver (29% of control) and kidney (42%), but severely decreased in brain (3%). These findings might explain the severity of neurological symptoms in the absence of marked organic aciduria. They indicate that in biotinidase deficiency the CNS may become biotin depleted earlier and more severely than other organs. Biotinidase deficiency should be included in the differential diagnosis of Leigh syndrome and of unexplained respiratory problems. PMID- 2587128 TI - Risk of injury to children less than 5 years of age in day care versus home care settings. AB - Recent studies have suggested that day care may be a relatively unsafe environment. In this population-based study, the incidence of injuries in day care and home care were evaluated based on the number of hours children were exposed to each environment. In this population, 43.6% of children less than 5 years of age spent part of the year in day care. The rate of injuries in day care was 2.50 per 100,000 child-hours of exposure compared with a rate of 4.88 per 100,000 child-hours of exposure in the home environment. There were no differences in overall severity of injuries in the two groups. It was concluded that children are at no greater risk of injury in day-care settings than in the home environment. PMID- 2587129 TI - Parental attitudes and practices toward children as pedestrians. AB - Community programs to reduce the toll from pedestrian injuries in childhood must include parents as a key element. This study, consisting of a survey questionnaire, was undertaken to provide information concerning current parent attitudes and practices that could be used to guide prevention programs. The survey consisted of 2464 questionnaires from parents of children in grades kindergarten to four in a suburban school district. Although 94% of parents did not believe that 5- to 6-year-old children can reliably cross streets alone, one third of parents allowed kindergarten-aged children to cross residential streets alone and first-grade children to walk alone to school. The presence of speeding traffic or the lack of safe places to walk did not influence parents in limiting their children's crossings. Few (17%) parents believed that children should be taught not to cross alone; one half of parents, including 41% of parents of kindergarten-aged children believed that children should be taught to cross busy streets without traffic lights. According to results of the study, parent expectations for their children's pedestrian skills may be inappropriate and may be a fruitful target for injury-prevention programs. PMID- 2587130 TI - Frequency and significance of physical evidence in legally proven cases of child sexual abuse. AB - Clinicians have long recognized and attorneys have disputed that physical evidence of injury, sexually transmitted diseases, and seminal fluid are often absent in cases of child sexual abuse. To determine the frequency and significance of physical evidence in legally "proven" felony cases with penetration, a retrospective review of sexual abuse court records was done. A total of 45 randomly selected cases were reviewed; 39 (87%) had resulted in conviction of the perpetrator for felony. Charges of vaginal rape were made in 32 cases, and charges of oral and/or anal sodomy in 23 cases. No significant difference in rate of felony conviction was found in cases with or without physical evidence. Of 32 cases without physical evidence, 30 (94%) resulted in felony convictions, whereas only 9 of 13 cases (69%) with physical evidence resulted in a felony conviction. Multiple variables describing the abuse situation were not shown to effect the legal outcome of the cases. Of cases that resulted in felony convictions, physical evidence was present in only 23% (9 of 39). These results should be helpful for the clinician in counseling the family of the sexual abuse victim and the attorney who prosecutes child sexual abuse cases. PMID- 2587132 TI - Sudden infant death syndrome in twins. AB - The incidence of sudden infant death syndrome is higher among twins than it is among singleton infants. Incidence of sudden infant death syndrome in twins in South Australia, is discussed, as well as some features of these twins and the health of the cotwins. The literature concerning the status of the cotwin is reviewed. PMID- 2587131 TI - Validity of the medical record for evaluation of telephone management. AB - The purpose of this study was to determine whether the medical record provides accurate documentation of the telephone encounter. The study was a "blinded" comparison of audiotaped telephone encounters and corresponding medical records; it was carried out in the continuity clinic of a primary care pediatric resident training program. During their first month of rotation through the outpatient department, 17 PL-I residents received one or two calls made by a "simulated mother" using standardized scripts. Transcripts of these calls and the corresponding written medical records were rated by an examiner unaware of the resident's identity. A standardized instrument was used to measure three aspects of performance: General History Taking, Specific History Taking, and General Management. A percentage of agreement was calculated for each scale, and rating scores of audiotapes and written records were compared. Twenty-seven pairs of audiotape and written documentation were analyzed. The mean percentage of agreement between audiotapes and written records was high: 78% for General History Taking, 78% for General Management, 77% for Specific History Taking. Rating scores of the audiotape and the medical record were significantly correlated for two of the scales: General Management (r = .55, P less than .01) and Specific History Taking (r = .50, P less than .01). Most aspects of the telephone encounter were well documented in the medical record. However, several discrepancies were noted when audiotapes and medical records were compared for the presence of specific items. With the exception of the Specific History Taking scale, there was no correlation between the length of the written record and the percentage of agreement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2587133 TI - Maternal administration of vitamin K does not improve the coagulation profile of preterm infants. AB - The effect of maternal administration of vitamin K1 on cord blood prothrombin time, activated partial thromboplastin time, activity of factors II, VII, and X, and antigen levels of factors II and X in infants less than 35 weeks' gestation was evaluated. Pregnant women in preterm labor were randomly assigned to receive 10 mg of vitamin K1 intramuscularly or no injection. If delivery did not occur in 4 days, the dose of vitamin K1 was repeated. Women who continued their pregnancy 4 days beyond the second dose received 20 mg of vitamin K1 orally daily until the end of the 34th week of gestation. The birth weights of infants ranged from 370 to 2550 g and gestational age ranged from 22 to 34 weeks. The prothrombin time, activated partial thromboplastin time, factors II, VII, and X activity, and factors II and X antigen levels were not statistically different in either group of infants. Intraventricular hemorrhage occurred in 25 of 51 control infants and 25 of 47 vitamin K-treated infants. More control infants had grade III intraventricular hemorrhage on day 1 (P = .032), but on day 3 and 14 of life, the severity of intraventricular hemorrhage was comparable in both groups. Infants in whom an intraventricular hemorrhage developed were significantly smaller, younger, and more critically ill than infants without intraventricular hemorrhage. Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation does not improve the hemostatic defects nor does it reduce the incidence or severity of intraventricular hemorrhage in their infants. PMID- 2587134 TI - Fever and petechiae in children. AB - A prospective study of patients with fever and petechiae was performed. Of 190 patients enrolled in the 1-year study, 13 (7%) had meningococcal disease. The most common bacterial association was Streptococcus pyogenes (19 patients). Viral infections were documented in 28 patients. Patients with invasive bacterial disease (group I) appeared more sick, were more likely to have signs of meningeal irritation, and were more likely to have petechiae on the lower extremities than those with less serious, nonbacteremic disease (group II). No patient in group I had petechiae only above the nipple line. Patients in group I had a significantly higher peripheral white blood cell count and absolute band form count. Although no laboratory test or physical finding was sufficiently sensitive to detect all patients with serious disease, the patient with abnormal cerebrospinal fluid, elevated white blood cell count, or elevated absolute band form count was at increased risk for invasive, bacterial disease. Conversely, the risk of serious disease was small if all of these values were in the normal range in the nonill appearing child or if sore throat and clinical pharyngitis were present in the patient older than 3 years of age. PMID- 2587135 TI - Thrombocytosis in childhood: a survey of 94 patients. AB - The introduction of the newer generation of electronic cell counters allows the routine reporting of platelet numbers when the peripheral blood count is requested. In a 12-month period, 100 episodes of marked thrombocytosis (platelet count more than 900 X 10(9)/L) were found among 94 children. These patients were young (median age 9 months). All but one episode of marked thrombocytosis occurred as a phenomenon secondary to a variety of disease states. Infections, especially those involving the central nervous systems were the commonest cause of an elevated platelet count in this series. Malignant diseases alone were rarely associated with thrombocytosis of this magnitude. The elevated platelet count began to decline at a mean of 3 days after diagnosis, and no thrombotic or hemorrhagic complications were encountered. Marked thrombocytosis is a benign, common phenomenon in young children, but specific treatment is not required. PMID- 2587137 TI - Pulmonary function tests and fluid balance in neonates with chronic lung disease during dexamethasone treatment. AB - Pulmonary function tests and fluid balance were measured serially during treatment with dexamethasone in seven ventilator-dependent, 14- to 27-day-old infants. The infants showed no improvement in respiratory status during the prior 5 days. Birth weights ranged from 540 to 900 g, with gestational ages of 24 to 26 weeks. The decision to treat the infants with dexamethasone was made by the clinical team. Pulmonary function tests were performed prior to the first dose and then every 12 hours until extubation. Significant differences were first seen after only 12 hours of treatment. Five infants were extubated within 48 hours of starting therapy. Before extubation at 48 hours, changes were found in dynamic compliance (74% increase), total pulmonary resistance by midvolume and regression methods (38% and 35% decreases, respectively), and expiratory time constant (49% increase), with P less than .01 in all cases. An increase in urine output was also observed in the first 12 hours. Improvements in chronic lung disease produced by dexamethasone are rapid and may result from dexamethasone-induced pulmonary fluid shifts. PMID- 2587136 TI - Isolated thrombocytopenia in children with acute lymphoblastic leukemia: a rare event in a Pediatric Oncology Group Study. AB - To determine how many children with acute lymphoblastic leukemia were initially referred to a pediatric hematologist because of isolated significant thrombocytopenia ([platelet count less than 50,000/mm3] and an otherwise normal complete blood cell count and physical findings), a retrospective review of the Pediatric Oncology Group's charts was undertaken. Review of the records of 2239 children enrolled in the past two acute lymphoblastic leukemia protocols showed that none of these children had significant thrombocytopenia with no other hematologic or physical manifestations of acute lymphoblastic leukemia when they were first seen by the hematologist. The results suggest that routine bone marrow aspiration in the child with isolated thrombocytopenia may be unnecessary to rule out acute lymphocytic leukemia. PMID- 2587138 TI - Neuropsychologic impairment in children with sickle cell anemia. AB - In this study, the neuropsychologic functioning of 21 children with sickle cell anemia and 21 sibling controls, age range 7 through 16 years, with no history of neurologic disease, was examined. Outcome measures included tests of intelligence, constructional praxis, memory, and academic learning. On the Wechsler Intelligence Scale for Children--Revised, the sickle cell group had a mean Full Scale IQ of 77.7 (SD 12.4) compared with 94.3 (SD 11.0) for the control group. The profile of test scores was similar for the two groups, with the sickle cell group scoring significantly lower than the control group on almost all cognitive measures. Both groups showed academic achievement to be commensurate with their measured intellectual ability. These results suggest that subtle but significant and widespread neuropsychologic deficits are associated with sickle cell anemia even in the absence of neurologic complications. When and by what process this neuropsychologic impairment is caused needs to be determined. PMID- 2587139 TI - Targeting of heme oxygenase inhibitors to the spleen markedly increases their ability to diminish bilirubin production. AB - Incorporation of heme oxygenase inhibitors into phosphatidyl choline liposomes markedly enhanced localization of these agents within the spleen as compared with the localization observed following their administration in aqueous vehicle. The increased concentration of inhibitor within splenic microsomes led to a near complete and sustained blockade of heme oxygenase activity and thus to a marked diminution in biliary bilirubin output. These studies suggest that heme oxygenase inhibitors administered within liposomes may so effectively block bilirubin production in the human newborn that ancillary methods for treating this important clinical problem may be reduced to a minimum. PMID- 2587140 TI - Generalized seizures in an infant due to environmentally acquired cocaine. PMID- 2587141 TI - Plasma aluminum measurements in term infants fed human milk or a soy-based infant formula. PMID- 2587142 TI - The secret. PMID- 2587143 TI - American Academy of Pediatrics Committee on Infectious Diseases. Measles: reassessment of the current immunization policy. PMID- 2587144 TI - American Academy of Pediatrics Committee on Nutrition: Iron-fortified infant formulas. PMID- 2587145 TI - American Academy of Pediatrics: PREP statement. PMID- 2587146 TI - American Academy of Pediatrics Committee on Adolescence: Health care for children and adolescents in detention centers, jails, lock-ups, and other court-sponsored residential facilities. PMID- 2587147 TI - Status epilepticus--risks and treatment. PMID- 2587148 TI - Worry in suburbia about acquired immunodeficiency syndrome! PMID- 2587149 TI - Schools and sex education. PMID- 2587150 TI - Cow's milk formula and infantile colic. PMID- 2587151 TI - Untreated bacteriuria in asymptomatic girls with renal scarring. AB - Recurrences of bacteriuria after treatment occur in 50% to 80% of asymptomatic patients. Previous experience with short-term treatment as well as long-term prophylaxis has been disappointing, with a significant risk of infections, ie, development of symptoms after treatment. Results with nontreatment are described in this report with reference to clinical course, renal growth, and glomerular filtration rate in 26 asymptomatic girls with established renal scarring and bacteriuria. Acute pyelonephritis was not seen in those with continuing bacteriuria or spontaneous clearance. Neither in scarred nor in unscarred kidneys did the duration of bacteriuria influence renal growth or glomerular filtration rate. Asymptomatic patients with bacteriuria may gain from nontreatment and may have a reduced risk of pyelonephritic attacks. PMID- 2587152 TI - Plasma cholesterol levels of 6585 children in the United States: results of the know your body screening in five states. AB - Medical and public health recommendations regarding detection and treatment of hyperlipidemia in children have generally been based on two principal epidemiologic studies: the Lipids Research Clinics Population Study (1972 to 1976) and the Bogalusa Heart Study (1973 to 1974). The present study was initiated to further describe the distribution of plasma cholesterol levels in a multiracial sample of American children. Between 1984 and 1988, the total cholesterol levels of 6585 children from 22 schools were measured as part of the Know Your Body School Health Program. For the entire population, ages 5 to 18 years, the mean total cholesterol concentration was 166.4 mg/dL. Total cholesterol was significantly greater in girls (168 mg/dL) than in boys (165 mg/dL), although sex differences were inconsistent across race/ethnicity. The mean value for blacks, 173 mg/dL, and Hispanics, 168 mg/dL, was higher than for Asians, 165 mg/dL, and whites, 163 mg/dL. Across race/ethnicity, values tended to peak between ages 8 and 10 years for girls and approximately 10 years of age for boys. These values are slightly higher than those reported in the Lipids Research Clinics and Bogalusa studies. Public health implications of these findings are discussed. PMID- 2587153 TI - Persistent bacteremia due to coagulase-negative staphylococci in low birth weight neonates. AB - During a 6-month period in 1987, 13 low birth weight neonates without indwelling central intravascular catheters had persistent (positive blood cultures for greater than or equal to 6 days) coagulase-negative staphylococcal bacteremia despite adequate antibiotic therapy. Daily blood cultures remained persistently positive for a mean of 13 days (range 6 to 25 days). This group of infants was compared with other low birth weight infants with similar birth weights and nonpersistent coagulase-negative staphylococcal bacteremia, defined as two or more positive blood cultures accompanied by supporting clinical manifestations of sepsis. During this period, coagulase-negative staphylococcal represented 29% of all bacteremias, and 33% of coagulase-negative staphylococcal bacteremias were persistent. Other than soft tissue abscesses, none of the infants with persistent coagulase-negative staphylococcal bacteremia had a defined focus of infection. Abdominal distention (P = .001) and thrombocytopenia (P less than .03) occurred significantly more frequently in the patients with persistent coagulase-negative staphylococcal bacteremia than in those with nonpersistent bacteremia. Of the 13 patients with persistent coagulase-negative staphylococcal bacteremia, 2 received methicillin and 11 received vancomycin. No antibiotic tolerance to either antibiotic could be demonstrated. Serum concentrations of vancomycin far exceeded the minimum bactericidal concentration in all cases in which vancomycin was prescribed. No in vitro differences could be demonstrated between persistent and nonpersistent coagulase-negative staphylococcal strains for slime production, biotype, proteins from modified whole cell lysates developed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and opsonophagocytosis by adult neutrophils in the presence of pooled human sera. Additionally, plasmid profile analysis and phage typing revealed no common strain causing the persistent bacteremia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2587154 TI - Acquired immunodeficiency syndrome educational program: effects on adolescents' knowledge and attitudes. AB - Although many schools are presenting acquired immunodeficiency syndrome (AIDS) education programs for adolescents, few have evaluated the effects of the programs. The effects of two different types of program presentation, a lecture or a film, were compared to a no-program condition. Students who received the lecture demonstrated significantly greater knowledge gains than either of the other two groups. The lecture group's greater gain was maintained at the 1-month follow-up, although all three groups showed a decline in knowledge scores from posttest to follow-up. Both educational programs significantly increased students' positive attitudes toward patients with AIDS; there were no differences between the two groups. Positive attitudes decreased equally for both groups from posttest to follow-up, although these scores remained significantly more positive than the pretest scores. Students in both treatment groups showed a slight increase in positive attitudes toward practicing preventive behaviors following the programs, but those attitude scores returned to baseline levels at follow-up. Although educational programs increase knowledge and positive attitudes toward patients with AIDS, they do not appear to have a positive effect on attitudes toward practicing preventive behaviors. More intensive programs may be necessary to encourage behavioral changes. PMID- 2587155 TI - Immunogenicity of Haemophilus influenzae oligosaccharide-protein and polysaccharide-protein conjugate vaccination of children at 4, 6, and 14 months of age. AB - At 4 and 6 months of age, 118 infants were vaccinated with either one of two Haemophilus influenzae type b capsular polysaccharide-protein conjugate vaccines: 72 infants received the polysaccharide coupled to diphtheria toxoid (PRP-D group), and 46 infants received polysaccharide-derived oligosaccharides coupled to CRM197 protein, a nontoxic mutant form of diphtheria toxin (HbOC group). A third dose of the same vaccine was given to 40 children in the PRP-D group and 25 children in the HbOC group at 14 months of age. Antibodies to the H influenzae type b capsular polysaccharide were measured by Farr-type radioimmunoassay in serum samples taken before each vaccination and 1 month after the second and the third doses. Adverse reactions monitored by a questionnaire were mild. After two vaccine doses, the geometric mean concentration of antibodies to H influenzae type b polysaccharide increased from 0.07 micrograms/mL in the prevaccination samples to 0.63 micrograms/mL in the PRP-D group and to 4.32 micrograms/mL in the HbOC group. In the following 7 months, the geometric mean concentrations declined to 0.38 and 1.12 micrograms/mL, respectively. The booster dose given at 14 months elicited a strong antibody response in both groups (to geometric mean concentrations of 29.7 and 58.3 micrograms/mL, respectively). Both vaccines appear to be capable of immunologic priming by immunization in infancy. PMID- 2587156 TI - [The main indicators of morphofunctional development of schoolchildren from the Carpathian region (Ivano-Frankovsk)]. PMID- 2587157 TI - [Indicators of the autoimmune component in newborn infants with pathology of the central nervous system]. PMID- 2587158 TI - [Correlations of various functional indicators in infants under 1 year of age with a high risk of developing sudden death syndrome]. PMID- 2587159 TI - [Use of the resochin test in pediatric rheumatology]. PMID- 2587160 TI - [Characteristics of the development of immunity in healthy children during the first year of life]. AB - Studies of the levels of serum IgA, IgG, and IgM, of B and T lymphocyte function in 20 neonates of days 7-8 of life (funic blood) and their mothers, in children aged 1,3,6,9 and 12 months made it possible to define the characteristic features of the establishment of humoral and cellular immunity during the first year of the child's life. The children placed under observation were normal as regards their physical and psychomotor development and had no infectious or inflammatory diseases. The neonates were characterized by high activity of T lymphocytes, the lack of IgA and traces of IgM, and the high level of IgG in blood serum. The least IgG concentration was seen at an age of 1 month. The data obtained will permit a proper assessment of the changes occurring in the child's immune status during different diseases. The changes should be taken into consideration in carrying out preventive and treatment measures during the first year of the child's life. PMID- 2587161 TI - [Membrane markers of T- and B-lymphocytes in children with primary immunologic deficiency conditions]. AB - Altogether 79 children with primary immunodeficiency conditions (PIC) and 21 children suffering from frequently occurring bacterial infections were examined for the level of rosette-forming cells and lymphocytes reacting positively with monoclonal antibodies to different phenotypic membranous markers (SD-antigens and others). The patients with combined forms of immunodeficiency, with T deficiency playing the key role manifested a significant lowering of the content of the subpopulations of SD3+, SD5+, SD7+ and SD4+ lymphocytes and the decrease of the SD4/SD8 ratio. The the reduction of the number of B lymphocytes (smIg + K1, SD19 +), the low levels of Ia+ -cells, and the decrease of the SD4/SD8 at the expense of the content of SD8+ -cells. In the patients with selective immunodeficiency and recurrent bacterial infections without verified PIC, these parameters did not undergo any essential changes. As compared with immunofluorescent assays, the measurement of E-RFL and M-RFL amounts was found to have insufficient information content for the diagnosis of PIC. PMID- 2587162 TI - [Characteristics of immunity in children with lymphoid hyperplastic diathesis]. AB - As many as 100 children aged 3 months to 4 years with lymphaticohypoplastic diathesis (LHD) were examined for clinico-immunologic++ interrelations. The children suffering from manifest LHD demonstrated the reduction of the amount of circulating T lymphocytes and IgA, IgM and IgG subpopulations. At the same time the changes in local immunity correlating with enlargement of the thymus and lymphoid formations in the nasopharynx were identified. The immunity unbalance in LHD was supported by morphologic and immunologic studies of the tissue of the removed hypertrophied tonsils. The specification of the deranged mechanisms of immunity in LHD requires early diagnosis of the illness, screening of the methods for immunocorrection and closer follow-up of the sick children. PMID- 2587163 TI - [Vaccination against diphtheria and tetanus of children with thymus hyperplasia syndrome]. AB - Inhibition of cellular and humoral immunity was established in children with grade I thymus enlargement syndrome (TES). The most pronounced changes were recorded in children aged 1-5 years. Vaccination against diphtheria and tetanus performed before the diagnosis of the TES was made were followed by satisfactory output of anatoxins, indicating the prospectiveness of the vaccination of the given children's group with DPT vaccine and DT- and DT-M-anatoxin. PMID- 2587164 TI - [Anti-measles humoral immunity in children with thymus hyperplasia]. AB - Analysis is made of the data obtained during clinical studies of the vaccinal process in 54 children with grades I-II thymus enlargement, vaccinated against measles. The clinical course of the vaccinal process in these children does not differ from the common course in normal children vaccinated against measles. The children with grades I-II thymus enlargement are capable of producing humoral antiviral immunity and of preserving high titres of antiviral antibodies for a long time. PMID- 2587166 TI - [Thrombocytic and erythrocytic components of hemostasis in bronchial asthma]. AB - Studies of the microcirculatory component of hemostasis in 44 children suffering from atopic bronchial asthma disclosed noticeable deviations of the parameters under study from the analogous ones in normal children. The most pronounced abnormalities were recorded in the paroxysmal period of the illness. Spontaneous aggregation of platelets should be regarded as the most sensitive test. Significant changes in the test were in agreement with the disease gravity and phase. PMID- 2587165 TI - [Characteristics of the clinical course of the post-vaccination period and the development of anti-measles immunity in children with allergic diseases]. AB - During vaccination of children suffering from allergic diseases with live measles vaccine, some characteristics of the clinical course of the postvaccinal period and specific immunity formation were defined. It has been shown that an individual approach to the immunization of the given children's group is very advantageous, since such a policy favours the lowering of the incidence of odd postvaccinal reactions and allergic complications as well as the output of measles antibodies. PMID- 2587168 TI - [Status of sanatorium and health resort services for children with non tuberculous diseases and the problems of their further improvement]. PMID- 2587167 TI - [Status of the autonomic nervous system and reflexotherapy in children with vasomotor rhinitis]. AB - Different variants of vegetative nervous system dysfunction were identified during the examination of 86 children with vasomotor rhinitis. Based on the findings of the examination a pathogenetically-based method of acupuncture was proposed for the management of this patients' group. Acupuncture with regard to vegetative dysfunction attenuated the latter's manifestations and corrected associated psychoemotional disorders. As a result the clinical manifestations of vasomotor rhinitis were eliminated. PMID- 2587169 TI - [Pathologic changes of the brain in children with various forms of infantile cerebral palsy (computerized-tomographic data)]. AB - Based on the clinical and computer-aided correlations a study was made of residual alterations in the brain of 110 children. There were 64 boys and 46 girls with different patterns of infantile cerebral paralysis (ICP). 67% of the examined manifested pathologic alterations on the tomograms (atrophy of the brain of varying intensity, areas of low density, cysts, porencephalia, and dysontogenic phenomena). The rate, character and the site of the pathomorphologic alterations slightly varied with different ICP patterns while the gravest alterations were seen on the computerized tomograms during double hemiplegia, in the hemiparesis and atonically astatic patterns of ICP. PMID- 2587170 TI - [Psychoautonomic syndrome in non-infectious subfebrile conditions in children]. AB - To ascertain the cerebral organization and the importance of its specific levels in the occurrence of the thermopathological syndrome associated with vegetovascular dystonia, 40 children aged 8-15 years with non-infectious subfebrile conditions of long standing were examined. The children's status was marked by polysystemic shifts common to the neurogenous disorders. Of crucial significance was dysfunction of the structures of the suprasegmental level (the limbic-reticular complex) of vegetative regulation with the involvement of the specialized hypothalamic centers of thermoregulation, with excessive sympathetic influences at the periphery and formation of the psychovegetative syndrome. An individual analysis of the psychovegetative syndrome makes it possible to define the contribution of the concrete endo- and exogenous factors to the pathogenesis of non-infectious subfebrile conditions and to develop a differential approach to the treatment. PMID- 2587171 TI - [Reaction of the autonomic nervous system of children to a magnetic field]. AB - A study was made of some reactions of the child's body to the magnetic field action with the aid of thermography, investigation of the parameters of vegetative functions and determination of the changes in the amount of the formed elements of white blood in 20 normal children and 20 patients aged 6-15 years suffering from chronic gastroduodenal diseases. It has been established that the changes in infrared radiation on the surface of the anterior abdominal wall in the patients mirror the adequacy of the compensatory reactions of the vegetative nervous system to the magnetic field action. The parameters of the function of the vegetative nervous system, mainly those of its sympathetic part, are indicative of the effect of the magnetic field on the patient's body. PMID- 2587172 TI - [Value of the study of the functional potential of neutrophils in suppurative, septic and allergic diseases in children]. AB - A method for measuring the content of cationic proteins in neutrophil granulocytes of the peripheral blood was employed in patients with pyoseptic (n = 12) and allergic (n = 28) diseases during the exposure to composite infections in vitro. The method enables one to assess the functional potentialities of the cells in mobilizing the internal reserves and the readiness for the trigger of the cellular granular apparatus, for instance during real or predicted exposure of the child to bacterial infections. The determination of the functional potentialities of neutrophil phagocytes can be used as a test for the appraisal of the gravity of allergic and pyoseptic processes as well as for predicting outcomes of pyoseptic diseases. PMID- 2587173 TI - [Ultrasonic methods of diagnosing infectious endocarditis in children]. AB - Ultrasound research methods were applied in 32 children with the clinical signs of infectious endocarditis (IE). The patients' age varied from 3 to 16 years. In 5 patients, IE turned out primary in the intact valves whereas in 27 patients, it superadded on different congenital heart disease. In 10 patients, IE had developed before surgical correction of the diseases and in 17, within different times after operation. The direct and indirect echo-signs of IE were delineated. The direct echo-signs included vegetations which were discovered in 22 out of the 32 patients. The indirect echo-signs included the signs of regurgitation in the externally unchanged or minimally changed cusps of the valves and blood drop at the level of the ventricles in connection with the defect reshunting in the interventricular septum. The data obtained are in good agreement with the clinical picture, surgical and morbid anatomy data. PMID- 2587174 TI - [Chronic colitis in children]. PMID- 2587175 TI - [Diagnosis of lesions of the thoracic organs in children with lymphogranulomatosis]. PMID- 2587176 TI - [The All-Union register of primary immunologic deficiency syndromes]. PMID- 2587177 TI - [Rehabilitation treatment of children in ambulatory-polyclinical conditions]. PMID- 2587178 TI - [Analytical review of the research in the field of pediatrics in 1988]. PMID- 2587179 TI - Effect of speaking rate on the perceptual structure of a phonetic category. AB - When listeners process temporal properties of speech that convey information about the phonetic segments of the language, they do so in a rate-dependent manner. This is seen as a shift in the location of the phonetic category boundary along a temporal continuum toward longer values of the acoustic property in question, as speech is slowed. In a series of experiments, we found that the adjustment for rate is not confined to the region of the category boundary, but extends throughout the phonetic category. Specifically, a change in rate modified the range of stimuli identified as members of a phonetic category, as well as which stimuli were overtly judged to be good exemplars of the category. These findings suggest that the listener's adjustment for speaking rate entails a comprehensive perceptual remapping between acoustic signal and phonetic structure. PMID- 2587180 TI - Pitch motion with random chord sequences. AB - Perception of global pitch motion was studied through psychoacoustic experiments with random chord sequences. Chords contained either six or eight (fixed) tone elements, being sinusoidal, sawtooth-like, or Shepard tones, which were either on or off according to a probability controlled by the experimenter. Sequences of 2, 4, 5, or 8 chords were used. Identification by subjects of the perceived direction of overall pitch motion (up or down) was found to be well accounted for by a model in which the ultimate pitch motion percept is given by a sum of contributions from selected element transitions--that is, transitions between adjoining tone elements in successive time frames only. In its simplest form, this dipole contribution model has only one free parameter, the perceptual noise for an element transition, which was estimated for various acoustic tone representations and chord arrangements. Results of two experiments, which were carried out independently in two different laboratories, are reported. PMID- 2587181 TI - Further experiments on the perception of growth in three dimensions. AB - Mark and Todd (1983) reported an experiment in which the cardioidal strain transformation was extended to three dimensions and applied to a three dimensional (3-D) representation of the head of a 15-year-old girl in a direction that made the transformed head appear younger to the vast majority of their subjects. The experiments reported here extend this research in order to examine whether subjects are indeed detecting cardioidal strain in three dimensions, rather than detecting changes in head slant or making 2-D comparisons of the shape of the occluding contour. Three-dimensional surfaces were obtained by measuring a real head manually (Experiment 1) and with a laser scanner (Experiment 2), and transformed to different age levels using the 3-D strain transformation described by Mark and Todd (1983). There were no statistically significant differences in the accuracy with which relative age judgments could be made in response to pairs of profiles, pairs of 3/4 views, or pairs of mixed views (profile plus 3/4 view), suggesting that subjects can indeed extract the cardioidal strain level of the head in three dimensions. However, an additional effect that emerged in these studies was that judgments were crucially affected by the instructions given to subjects, which suggests that factors other than cardioidal strain are important in making judgments about rich data structures. PMID- 2587182 TI - Visual adaptation to a spatial contrast enhances visual evoked potentials. AB - The effects of adaptation to the visual contrast of a counterphase grating were studied with visual evoked potentials (VEPs). The spatial frequency of the grating was 4 cpd, and its temporal frequency was 4 or 12 Hz. Steady-state VEPs were analyzed through an FFT (fast Fourier transform) algorithm. In the first experiment, contrast thresholds rose strongly just after the end of adaptation and declined regularly over time. The VEPs recorded in the medio-occipital lead showed an initial decrease in amplitude after adaptation, followed by an enhancement well above the preadaptation level and then a return to that level. The paradoxical enhancement of the VEP was found at both high and low contrast in both the medio-occipital lead and the right temporal lead of a right-handed subject. The left temporal leads showed a VEP enhancement at high contrast and a decline at a low value. PMID- 2587183 TI - Simultaneous sampling and length contrast. AB - The illusion of perceived line length produced by the parallel lines configuration reverses from assimilation to contrast with large spatial separation of the contextual and test lines (Jordan & Schiano, 1986). In the present experiment, we tested whether length contrast is produced by the sequential sampling of contextual and test lines or by the simultaneous sampling of the stimuli from a spatially distributed attentive field. Scanning instructions were manipulated such that one group of observers was encouraged to sample the lines sequentially, and a third group was given no specific scanning instructions. The data indicated that the reversal to length contrast is produced by simultaneous sampling of contextual and test lines. Implications for attentional descriptions of visual illusions are discussed. PMID- 2587184 TI - Aging is associated with increased Weber ratios for caffeine, but not for sucrose. AB - To investigate whether age-associated changes in the human taste system are quality-specific, we compared young and elderly subjects' suprathreshold discrimination abilities for caffeine and sucrose. The method of constant stimuli was used to obtain just noticeable differences and Weber ratios. The elderly generated larger Weber ratios than did the young for both the medium and high concentrations of caffeine, but not for the low concentration. For example, a 74% increase in .005 M caffeine was required to obtain a perceptible difference for the elderly, whereas a 34% increase produced a perceptible difference for the young. The Weber ratios for sucrose did not differ for the two age groups. The results of this study indicate that age-associated changes in the taste system are quality-specific. PMID- 2587185 TI - Do background luminances interact during binocular fusion? AB - The question investigated in the experiments reported here was whether monocular background luminances sum during binocular fusion. Fusion was made explicit by using a random-dot stereogram (RDS) as a background stimulus. In the presence of the RDS, differential luminance thresholds were somewhat higher than in the uniform field: a full-field, binocular dot array acted as a mask for a full-field luminance change, but global depth had no effect at threshold. The amount of the binocular advantage at threshold was compared to the basic "threshold response," that is, the change in threshold resulting from raising the background luminance by a factor of 2. It was found that the amount of the binocular advantage was equivalent, on the average, to some 75% of the threshold response--significantly less than the 100% predicted by "simple summation." The amount of the binocular advantage varied substantially among observers and eyes, whereas the threshold response obeyed Weber's law in all cases: the variability was eye-, rather than threshold-dependent. Monocular thresholds did not decrease when taken with the nontest eye occluded rather than viewing a fused background. The proposition that the adaptation state of the visual system is increased during binocular fusion (Cogan, 1982) was not supported. Yet occluding the nontest eye, rather than presenting the test stimulus monocularly against a fused background, did change monocular thresholds in some eyes and observers. These findings are interpreted as evidence for a complex binocular background interaction involving both summation and inhibition. PMID- 2587186 TI - Dichotic, diotic, and monaural summation of loudness: a comprehensive analysis of composition and psychophysical functions. AB - In a series of six experiments, the method of magnitude estimation, constrained by a multivariate model, was used to assess the rules that govern the summation of the loudness of two-tone complexes. This methodology enabled us to specify the amounts of summation and simultaneously to construct the corresponding loudness scales. The components had different frequency separations and in the different experiments were presented (1) dichotically, a different frequency to each ear; (2) diotically, to both ears; and (3) monaurally. Results replicated and in some conditions extended known features of multiple signal processing by the auditory system. Thus, qualitatively different rules of loudness integration appeared. For monaural and diotic modes of stimulation, overall loudness depended on total sound energy within the critical band, but on the simple sum of component loudnesses beyond the critical band. For dichotic presentations, a fully additive rule of loudness summation appeared, regardless of frequency spacing. For the latter (but not the former), loudness summation was perfect, with the underlying loudness scales closely approximating Stevens's sone scale. PMID- 2587187 TI - Extraretinal information about eye position during involuntary eye movement: optokinetic afternystagmus. AB - Despite importance for theories of perception, controversy exists as to whether information is available to the perceptual system about involuntary as well as voluntary eye movements. We measured the perceived direction of targets flashed briefly in an otherwise dark field during the primary phase of optokinetic afternystagmus (OKAN), an involuntary eye movement that persists in darkness following optokinetic stimulation. Perceived direction was measured by unseen pointing in one experiment and by pointing made under visual control in a second experiment. Pointing was essentially veridical in both experiments, indicating that accurate extra-retinal information about eye position (presumably, as efference copy) exists for OKAN. Illusory motion of visual targets, which can occur during involuntary oculomotor responses, therefore cannot be attributed to a lack of efference-copy signals for such eye movements. PMID- 2587188 TI - Illusions and aftereffects of length in the minimal form of the parallel-lines configuration: a reexamination. AB - A number of recent studies have used the graded-series method to measure the illusion and aftereffect distortions of perceived length in the minimal form of the parallel-lines configuration. However, because of some peculiar characteristics of the graded-series method, the aftereffect distortions measured with this method cannot be interpreted unequivocally as reflecting distortions of the perceived length of the test line. On the basis of the results of an experiment that examined the contribution of a possible confound present in the method, it is argued that the method should not be used to measure length aftereffects, and, furthermore, that the results of studies using this method need to be reconsidered. PMID- 2587189 TI - Effect of familiarity and category contrast on stimulus and response priming. AB - In a letter-symbol classification task, flanking incompatible symbols slowed response latencies to letter targets, whereas incompatible letter flankers did not slow the classification of symbol targets. The conditions surrounding this asymmetry in response competition were investigated in five experiments. The results showed that: (1) the asymmetry was not related to the familiarity of the symbol targets or to the prime-target interval; (2) when the classification involved familiar and unfamiliar symbols, the asymmetry remained (i.e., there was less interference associated with the unfamiliar symbol targets), but there was now significant response competition associated with both symbol categories; and (3) with a mixed-category task (i.e., letters and symbols assigned to both responses), the symbol targets continued to be less interfered with by both letter and symbol incompatible flankers. These findings were interpreted as suggesting that response competition can be influenced by both classification decision rules and cohesiveness of exemplars comprising a category. PMID- 2587190 TI - Shift in stimulus range and the exponent of the power function for loudness. AB - The exponent of the power function for loudness was tracked over the course of 60 trials with one stimulus range and compared to the exponent over the course of 60 subsequent trials with a different stimulus range. Three stimulus sets were used: (1) weak, a short range of relatively soft tones (45-55 dBA); (2) strong, a short range of relatively loud tones (64-74 dBA); and (3) complete, a longer range of soft to loud tones (40-90 dBA). All pairs of stimulus sets were tested, together with three control conditions in which no shift in range occurred. Ten subjects were run in each of the nine groups. For preshift trials, the mean exponent was lowest for the strong stimulus series, highest for the weak series, and at an intermediate value for the complete series. These differences were all significant. Following a shift in stimulus range, the weak series still yielded the highest exponent, but the exponents were not reliably different for the complete and strong series. Postshift exponents also depended significantly on the preshift range experienced by the subjects. These effects were not confined to the period immediately following the shift in range, but persisted for up to 60 trials. PMID- 2587191 TI - [Risk-benefit analysis for mass screening of breast cancer utilizing mammography as a screening test]. AB - Incidence of breast cancers in Japanese women is increasing steadily. Mass screening of breast cancer was started in Japan under auspices of Adult Health Promotion Act of the Japanese Government from 1987. As the first screening method, the palpation of breasts is employed at present, but it is expected to be replaced by the mammography. In this report, the risk-benefit analysis is presented between risk of breast carcinogenesis due to radiation and benefit of mass screening of breast cancer. The benefit of mass screening is taken as the net elongation of average life expectancy of women due to survival from breast cancers. The risk of mammography is taken as the net loss of average life expectancy of women due to breast carcinogenesis. In the latter, the latency time and plateau period of radiation carcinogenesis were taken into consideration in the calculation. The results show that the ages at which the benefit and risk become equal are between 30 and 35 years old when dose equivalent of mammography is between 10 and 20 mSv, that are conventionally used. However, the critical age will be reduced to 20 years old if the dose equivalent becomes 1 mSv. Therefore, it is strongly recommended that a low dose mammographic system should be developed in order to achieve 1 mSv for the mass screening of breast cancer of Japanese women. In author's opinion, this is quite feasible by employing a new digital radiography with imaging plate. PMID- 2587192 TI - [Sequential MRI and CT monitoring in cryosurgery--an experimental study in polyvinyl alcohol gel phantom]. AB - The purpose of this investigation is to detect a cryolesion by MRI and CT during cryosurgery. A fundamental study was performed to demonstrate MR and CT images of polyvinyl alcohol (PVA) gel, which was used as a phantom for MRI, under the condition of low temperature. MRI was performed on a 0.1 Tesla system (ASAHI MR Mark-J). As the temperature lowered, the unfrozen PVA gel showed decreases in T1 and T2, and an increase in signal intensity on the low flip (LF) angle images, which were obtained using 60 degrees of flip angle, Tr of 100 msec, Te of 18 msec with gradient echo acquisition method. The frozen PVA gel showed no signal intensity on the LF images and zero in T1 and T2. On the other hand, the CT images revealed the frozen area of the PVA gel as a hypodense area. From the facts described above, it may be concluded that MRI and CT will be able to detect cryolesions during cryosurgery. PMID- 2587193 TI - [Urinary tract involvement from pancreas carcinoma]. AB - Pancreas carcinoma is sometimes notoriously difficult to diagnosis. It is well known that pancreas carcinoma can invade contiguous organs, but no attention for urinary tract involvement is paid. Urinary tract is involved at a late stage but may represent the first symptomatic evidence of disease. In such case, pancreas carcinoma can be presented initially as urologic disease and patients' symptom may not be differentiated from urinary tract disease. Computed tomographic (CT) images and medical records of 50 patients with histologically proved pancreas carcinoma were reviewed. There were 10 cases with urinary tract involvement. Those of 8 were male and 2 were female. There was a high incidence of left urinary tract involvement (left:right:bilateral = 7:2:1). Although 9 cases were pancreas body and tail carcinoma, 1 case was pancreas head carcinoma. And those stages were all in IV. All cases have confirmed evidence of urinary tract involvement at autopsy within 4 months following CT studies. IVP study was performed in 8 of these cases. We compared those IVP, CT images and findings of autopsy. In those patients, 4 cases showed direct invasion of the kidney, 5 cases showed ureteral involvement and 1 case showed metastasis to the urinary bladder and ureters. IVP showed inferior displacement of the kidney and/or ureteral displacement on the affected side. And also, collecting system distortion was demonstrated, including hydronephrosis secondary to ureteral compression. CT scan showed abnormal mass which is contiguous to the pancreas, showing compression the kidney and/or retroperitoneal extension with ureteral involvement. Metastasis to the urinary bladder is also identified. The findings of autopsy were almost the same of the CT findings. Pancreas carcinoma characteristically remains silent until little chance for cure. Although urinary tract involvement is rare, it can mimic renal and ureteral pathology. In differential diagnosis of urinary tract lesion, the disease process originated from pancreas should be included as well as from contiguous structures. PMID- 2587194 TI - [Pulmonary infarction associated with bronchogenic carcinoma]. AB - Pulmonary infarction may be associated with bronchogenic carcinoma. Radiopathological correlation was performed in four patients. There were two cases of squamous cell carcinoma, one case of adenocarcinoma and one case of large cell carcinoma. Infarcts in patients with squamous cell carcinoma were obscured on plain radiographs by a large primary tumor or atelectasis of the affected lobe. Infarcts in adenocarcinoma and large cell carcinoma were clearly demonstrated on plain radiographs; 1 to 2 cm in size, round or polygonal in shape, blurred in margin, and located at the periphery of the same lobe as the primary tumor. Rapid appearance of infarcts was helpful in distinguishing from intrapulmonary metastasis. Invasion of the pulmonary artery, pulmonary vein and bronchial wall in hilar region was thought to be responsible for pulmonary infarction. Pulmonary infarct should be considered in patients with centrally invasive bronchogenic carcinoma, when a small ill-defined opacity appears at the periphery of the involved lobe over a short period. PMID- 2587195 TI - [MR images of wallerian degeneration--relation between the time and MR findings of wallerian degeneration]. AB - On magnetic resonance (MR) images, wallerian degeneration of the pyramidal tract can be demonstrated as an abnormal intensity showing prolonged T1 and T2 relaxation times corresponding to the corticospinal tract, and/or as shrinkage of the ipsilateral cerebral peduncle and pons. We evaluated 150 cases with supratentorial cerebrovascular accident (CVA) and found the above findings in 35 patients (hematoma 21, infarction 14). The time interval between the ictus of CVA and manifestation of wallerian degeneration on MR images was evaluated. In all 35 cases the foci of CVA located at or extended into the motor cortex, the corona radiata of the pyramidal tract or the posterior limb of the internal capsule. Abnormal signal intensity appeared as early as 5 weeks after ictus and was observed in all 17 cases after 10 weeks. Ipsilateral shrinkage of the cerebral peduncle and the pons has appeared 13 months after ictus. MR appears to be the most useful modality for early detection of waller degeneration. PMID- 2587197 TI - Toward a caring curriculum: a new pedagogy for nursing. PMID- 2587196 TI - [Experimental study of embolo-hyperthermia for treatment of liver tumor- induction heating to ferromagnetic particles injected into tumor tissue]. AB - Hepatic arterial embolization was performed on VX2 liver tumor of rabbit with subsequent induction heating to the tumor. Prior to the heating, iron particle suspension was injected into tumor tissue as a target of induction heating (500 KHZ, 9 KW). The temperatures of the tumor and liver parenchyma were measured with fluoroptic thermometer. Elevation of the tumor temperature during initial heating for 6 minutes were well correlated to the dose of iron particles injected; 1.4 degrees C with 1 g, 3.0 degrees C with 2 g, and 4.9 degrees C with 3 g. The temperature of liver parenchyma were below 39 degrees C even with 3 g injection. PMID- 2587198 TI - A new age exemplar curriculum paradigm. Making the connection: teacher-student interactions and learning experiences. PMID- 2587199 TI - Hairy cell leukemia: follow-up after completion of alpha interferon treatment. AB - Between May 84 and December 85, 61 patients were treated for hairy cell leukemia by (recombinant or natural) alpha-IFN in a single institution. The responses obtained after 7 or 12 months of treatment are presented and the follow-up of the 39 patients for whom the treatment had been stopped for more than 12 months is evaluated. Neither clinical or histological parameters at presentation nor the type of timing of the interferon used allowed to predict the quality of response. The median time-lapse before the occurrence of neutropenia below 1.10(9)/l in patients with normal blood counts at the end of treatment was 12 months. However early relapses after the treatment stop were observed more frequently in patients with initially severe neutropenia or hyperleucocytosis. The therapeutic strategy in hairy cell leukemia is discussed. PMID- 2587200 TI - Failure of amphotericin B spray to prevent aspergillosis in granulocytopenic patients. AB - We tested the efficiency of a nasal spray of Amphotericin B (AmB) in leukemic patients, in an attempt to prevent pulmonary Aspergillosis. From January to July, 8 cases of invasive Aspergillosis (IA) in 19 new leukemic patients were identified. Between July and September 15 patients were treated by prophylactic nasal spray of AmB (daily dose 5 mg). Compliance was excellent, but nevertheless typical IA developed in 5 patients. We conclude that at the dosage used prophylactic administration of nasal spray of (AmB) does not prevent IA. PMID- 2587201 TI - High serum interleukin-2 levels in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. AB - Interleukin-1 (IL-1), Interleukin-2 (IL-2) and soluble receptors for IL-2 (sIL 2R) play a crucial role in the immune response. IL-2 in particular is implicated not only in T-cell proliferation but also in normal B-cell proliferation and differentiation and in the development of B and T cell malignancies. We have assayed the serum levels of IL-1, IL-2 and sIL-2R in 12 patients with monoclonal gammopathy of undetermined significance (MGUS) and 44 patients with multiple myeloma (MM). Sera collected from 40 healthy blood donors were used for normal values, and sera from 33 medical volunteers over 48 years of age (median age 52 years) for normal IL-2 values in the elderly. Mean IL-2 serum values were 6.50 U/ml in MGUS and 4.97 U/ml in MM patients. There was a statistical significant elevation of IL-2 levels is both MM and MGUS patients when compared to both normal controls (p less than 0.001, Wilcoxon two tailed test). A significant difference in IL-2 levels (p less than 0.025) was also observed between MGUS and MM patients. The levels of serum IL-1 and sIL-2R were normal both in MGUS and MM patients. In 24 MM patients where the dosage of serum beta-2-microglobulin was available, a significant difference (p less than 0.01) in serum IL-2 levels was found between patients with beta-2-microglobulin greater than 6 micrograms/ml and less than 6 micrograms/ml. Pathogenic mechanisms as well as their possible clinical significance are discussed. PMID- 2587202 TI - Analysis of parameters for maximal in vitro proliferation and activation of lymphokine-activated killer cells (LAK). AB - In 15 patients (11 adults, 4 children) who received IL-2 and LAK cell therapy, we analyzed the different culture conditions which could either improve LAK cell activation and proliferation or which could simplify the procedure. Each parameter was assayed on a large scale and compared to standard culture conditions. Indomethacin had no effects, either positive or negative, on proliferation and activation of the cells. Culturing with 10% AB serum increased proliferation but did not modify total lytic activity compared to 2% AB serum. When cells were cultured in a medium with 2% autologous plasma obtained before any treatment, their proliferation was similar to that obtained in medium supplemented with 2% AB serum but the LAK activity was significantly higher. Autologous plasma obtained at day 8 of treatment (48 h after the first cycle of IL-2 and the day of the first cytapheresis) gave similar results to 2% AB serum. None of the 12 patients showed negative effects suggesting the presence of suppressive factors in the sera. Culturing with autologous plasma in clinical trials will lead to a 25% decrease in the total cost of culture and suppress the risk of viral contamination. Excess of granulocytes in the culture (greater than 30%), if the total nuclear cell concentration did not exceed 3 . 10(6) per ml, induced a better proliferation of mononuclear cells without modification of the activation. These results could be due to the liberation of factors by polynuclear cells, or to the loss during elimination of the granulocytes by the Ficoll separation of cells with similar density supporting LAK activity. PMID- 2587203 TI - Acute monocytic leukemia with B cell markers expression following B chronic lymphocytic leukemia. AB - A case of chronic lymphocytic leukemia (CLL) treated with chlorambucil, followed by the development of an acute monoblastic leukemia, is described. Cytofluorometric quantitative immunophenotype was determined during the blastic phase. Whereas small lymphocytes displayed a CD19+; CD24+; CD37+; CD5+ phenotype, the blastic population exhibited, besides CD13, CD14 and CD15 positivity, which is usually noted in such a monoblastic leukemia, definite CD9, CD10, CD22, CD24, CD37, CD5 and CD4 staining. Such results argue against a complete independence between the two clones, although their similarity could not be demonstrated. PMID- 2587204 TI - IgG subclass deficiency in acute myeloid leukemia. AB - Serum IgG subclass levels were measured using a competitive indirect immunoenzymatic assay with monoclonal antibodies in 22 acute myeloid leukemia patients at presentation and prior to specific therapy. Three patients had moderate IgG1 deficiency and 1 moderate IgG3 deficiency. Two of the three IgG1 deficient patients (and only one other) failed to respond to induction chemotherapy and the third died of bone marrow aplasia during induction. PMID- 2587205 TI - Kinetics of adriamycin injected proximal to a tumor: a comparative study between venous and arterial injections. AB - A kinetic study of plasma concentration of Doxorubicin (Adriamycin) was performed in 25 cases of malignant melanoma of the extremity with malignant adenopathy, treated with the same dose (20 mg per m2). Drug concentration was measured using a radioimmunoassay, with good intra-assay and inter-assay reproducibility. The kinetic analysis used the multiple compartmental method and a simulation of the plasma curves. Adriamycin injected intravenously quickly leaves the plasma into an exchangeable compartment with a slow plasma return and subsequent prolonged mean duration of the plasma half life at a low concentration. Thus, the intravenous perfusion results in a high plasma concentration only during the time of infusion. After intra arterial injection proximal to the tumor, a fraction variable (average 35%) is not released back into the circulation, or released very slowly. This local sequestration (important in terms of local concentration) explains the efficiency and the potential local toxicity of this method of administration. The rapid release of about 70% of the drug into the plasma, with kinetics similar to that observed after intravenous infusion, allows for no significant reduction of systemic toxicity. PMID- 2587207 TI - Congenital cyanosis due to methemoglobin reductase deficiency: first reported Tunisian case. AB - During investigation of chronic cyanosis in a 25 year old male, after excluding pulmonary and cardiac causes, methemoglobinemia was suspected. Investigation of the activity of methemoglobin reductase clenched the diagnosis of homozygous cytochrome b5 reductase deficiency in a case of recessive congenital methemoglobin type I (absence of neurologic symptoms). PMID- 2587206 TI - Activated partial thromboplastin time performed on capillary blood. AB - Activated partial thromboplastin time is one of the most frequently used assay in haemostasis investigation, but sampling of venous blood is often difficult in newborns (as well as some adult patients). We analysed a method described by Zondag et al [9] performed on capillary blood samples. We studied normal adults and newborns, patients with liver diseases, and those receiving therapy with vitamin K antagonists and heparin. Capillary assay was correlated with venous blood in normal subjects, in patients with liver diseases and during therapy by vitamin K antagonists. However results both in newborns and adults during heparin therapy were not accurate. PMID- 2587209 TI - Celiac disease revealed by an acute folate deficiency. CESA. Committee of expert for specific investigations in complex anemias. PMID- 2587208 TI - Myeloproliferative disorders in the department of Cote d'Or between 1980 and 1986. AB - By the registry of hematopoietic malignancies in Cote d'Or we studied the 177 cases of myeloproliferative disorders diagnosed between 1980 and 1986, divided into 4 groups: chronic myelogenous leukemia, idiopathic myelofibrosis, polycythemia vera, essential thrombocythemia. The global standardized rates based on the world population were 3.5 per 100,000 in men and 1.9 in women (sex ratio = 1.8). The mean age for myeloproliferative disorders was 61 +/- 16 years. Incidence was slightly higher in urban than in rural areas (NS). The most common means of detection were routine hemogram, fatigue and thrombosis. Five-year survival curves showed large differences in prognosis, from 30% for chronic myelogenous leukaemia to 83% for polycythaemia vera. PMID- 2587210 TI - Primary structure differences between proteins C1 and C2 of HeLa 40S nuclear ribonucleoprotein particles. AB - Partial acid cleavage, comparative HPLC tryptic peptide mapping and amino acid sequencing of the C1 and C2 proteins of HeLa heterogeneous nuclear ribonucleoprotein (hnRNP) particles demonstrate that proteins C1 and C2 differ in primary structure by the presence of a 13 amino acid insert sequence in C2. This C2 insert sequence occurs after either glycine 106 or serine 107 in C1. The additional 13 amino acids that are present in C2 account for the observed molecular weight difference between the C1 and C2 hnRNP proteins on SDS polyacrylamide gel electrophoresis. Because C1 and C2 appear identical except for the 13 residue insert and because the 3' and 5' untranslated regions of the corresponding mRNAs also appear to be the same (Swanson et al., Mol. Cell. Biol. 7: 1731-1739), it is possible that both polypeptides are produced from a single transcription unit through an alternative splicing mechanism. PMID- 2587211 TI - The ubiquitous nuclear protein, NHP1, binds with high affinity to different sequences of the chicken vitellogenin II gene. AB - In gel shift assays, affinity chromatography-purified NHP1 forms a stable complex with different sequences of the chicken vitellogenin II gene. The apparent KD of NHP1 with the estrogen response element (ERE) containing 5-methylcytosine is 1 X 10(-11) M. NHP1 does not form a complex with the Xenopus vitellogenin ERE where the GCG bases are replaced by CAG. NHP1 is closely related if not identical to the other ubiquitous proteins NHP2, NHP3 and NHP4 that bind specifically to different sequences. All four proteins behave identically on chromatography and give identical patterns in proteolytic bandshift assays. NHP1, NHP2 and NHP3 have a native molecular weight of 170,000 and are composed of two polypeptides of 85 and 75 kDa. The possible function of NHP1 is discussed. PMID- 2587212 TI - A computer program for choosing optimal oligonucleotides for filter hybridization, sequencing and in vitro amplification of DNA. AB - A method is presented for choosing optimal oligodeoxyribonucleotides as probes for filter hybridization, primers for sequencing, or primers for DNA amplification. Three main factors that determine the quality of a probe are considered: stability of the duplex formed between the probe and target nucleic acid, specificity of the probe for the intended target sequence, and self complementarity. DNA duplex stability calculations are based on the nearest neighbor thermodynamic values determined by Breslauer et al. [Proc. Natl. Acad. Sci. U.S.A. (1986), 83: 3746]. Temperatures of duplex dissociation predicted by the method described here were within 0.4 degrees C of the values obtained experimentally for ten oligonucleotides. Calculations for specificity of the probe and its self-complementarity are based on a simple dynamic algorithm. PMID- 2587213 TI - Reinvestigation of deoxyribonucleoside phosphorothioites: synthesis and properties of deoxyribonucleoside-3' dimethyl phosphites. AB - Further investigation of the synthesis of deoxyribonucleoside-3' (t-butyl) O-(2 cyanoethyl) phosphorothioites as monomer building units for the phosphorothioite approach has led us to conclude that internucleotidic bond formation proceeded via bis(deoxyribonucleoside-3') (2-cyanoethyl) phosphite intermediates, which proved to be activated by iodine, rather than the mechanism previously reported. In connection with this study, deoxyribonucleoside-3' dimethyl phosphites were synthesized and detailed properties of them are also described. PMID- 2587214 TI - Two highly conserved transcribed regions in the 5S DNA repeats of the nematodes Caenorhabditis elegans and Caenorhabditis briggsae. AB - The 5S RNA genes of Caenorhabditis briggsae consist of approximately 65 copies of a 1 kb repeat unit and 20 copies of a related 0.7 kb repeat unit, organized in separate tandem clusters. DNA sequence comparisons with the 1kb 5S DNA repeat from the closely related nematode C. elegans show that the 5S RNA coding region is perfectly conserved. Both C. briggsae 1 kb and 0.7 kb repeats are also efficiently transcribed in vitro,suggesting that both represent functional 5S RNA genes. Surprisingly, a second block of 118 bp is also perfectly conserved between the 1 kb repeats,and is less well conserved in the 0.7 kb repeat. In C. elegans, this DNA is transcribed to produce and abundant 100 nt transcript (SL RNA) which participates in a trans-splicing process (Krause and Hirsh, Cell 49:753, 1987). This SL RNA region of the C. briggsae 1 kb 5S DNA repeat also appears to be transcribed in vivo, while the corresponding region of the 0.7 kb repeat is not. PMID- 2587215 TI - Cooperativity in nucleosomes assembly on supercoiled pBR322 DNA. AB - Many studies have shown that in reconstituted chromatin model systems, containing only purified DNA and histone octamer, nucleosomes can adopt well defined locations with respect to DNA nucleotide sequence. Recently, nucleosome nucleosome interactions were suggested as one of the factors underlying preferential nucleosomes positioning. In the present paper this aspect has been studied by topological analysis and electron microscopy visualization of minichromosomes reconstituted at different histone/DNA ratios. Both methods suggest that cooperativity plays a role in nucleosomes formation. A linear cooperative model in which nucleosomes are formed on discrete sites with cooperative interactions occurring only between nearest neighbours allows to calculate the cooperative constant. The reported results show that basic interactions, which are of relevance in the process of chromatin folding, are present also in very simple model system. PMID- 2587216 TI - Sequence-dependent DNA curvature: conformational signal present in the main regulatory region of the rat mitochondrial genome. AB - Theoretical analysis and experimental approaches by gel electrophoresis in retarding conditions allowed us to identify the presence of an intrinsic bending in the D-loop containing region of the rat mitochondrial genome. The curvature was located in the right domain of the sequence analyzed, between the origin of replication of the heavy strand and its promoter. The preliminary evidence of a specific recognition of the bent DNA with mitochondrial matrix proteins suggests a probable role of this DNA conformation in the duplication and/or expression of the mammalian mitochondrial genome. PMID- 2587217 TI - ABR, an active BCR-related gene. AB - The human BCR gene on chromosome 22 is specifically involved in the Philadelphia translocation, t(9;22), a chromosomal rearrangement present in the leukemic cells of patients with chronic myeloid leukemia or acute lymphoblastic leukemia. In most cases, the breakpoints on chromosome 22 are found within a 5.8 kb region of DNA designated the major breakpoint cluster region (Mbcr) of the BCR gene. Hybridization experiments have indicated that the human genome contains BCR gene related sequences. Here we report the molecular cloning of one of these loci, for which we propose the name ABR. In contrast with the other BCR-related genes studied to date, ABR represents a functionally active gene and contains exons very similar to those found within the Mbcr. Unlike the BCR gene, the ABR gene exhibits great genomic variability caused by two different variable tandem repeat regions located in two introns. All other BCR gene-related sequences isolated so far and the BCR gene itself are located on chromosome 22. In contrast, the ABR gene is located on chromosome 17p. PMID- 2587219 TI - Nucleotide sequence of the human NAD-dependent methylene tetrahydrofolate dehydrogenase-cyclohydrolase. PMID- 2587218 TI - A common protein binds to two silencers 5' to the human beta-globin gene. AB - The temporal sequence of expression of human globin genes during development suggests precise regulation of these genes. Recent studies have characterized a number of DNA sequences within or flanking the human beta-globin gene which are important in its regulation and several proteins which bind to these sequences have been identified. We have found two proteins which bind 5' to the human beta globin gene. One of these proteins, which we designate BP1, binds to two sequences, one between -550 and -527 bp relative to the cap site, the other between -302 and -294 bp. A second protein, BP2, binds to sequences between -275 and -263 bp. The binding sites for both BP1 and BP2 are in two regions which function as silencers in a transient expression assay using the human erythroleukemia cell line K562. These results and others presented here suggest that BP1 may act as a repressor protein. Negative regulation seems to be an important component of tissue and developmental specific globin gene regulation. PMID- 2587221 TI - Nucleotide sequence of rice dwarf virus segment 5. PMID- 2587220 TI - Nucleotide sequence of the human ornithine decarboxylase gene. PMID- 2587222 TI - Nucleotide sequences of mouse histone genes H2A and H3.1. PMID- 2587223 TI - Structure of human muscle (beta) enolase mRNA and protein deduced from a genomic clone. PMID- 2587224 TI - Nucleotide sequence of the Thermus thermophilus HB8 gene coding for elongation factor G. PMID- 2587225 TI - Cloning and sequencing of the gene encoding the outer surface protein A (OspA) of a European Borrelia burgdorferi isolate. PMID- 2587226 TI - Nucleotide and deduced amino acid sequences of bacteriophage T4 gene 22. PMID- 2587227 TI - Sequence of a cDNA encoding soybean basic 7S globulin. PMID- 2587228 TI - Complete nucleotide sequence of LTR, v-src, LTR provirus H-19. PMID- 2587229 TI - cDNA sequences of two beta-globin genes in a Sprague-Dawley rat. PMID- 2587230 TI - Nucleotide and deduced amino acid sequences of staphylocoagulase gene from Staphylococcus aureus strain 213. PMID- 2587231 TI - cDNA for bovine type 1 plasminogen activator inhibitor (PAI-1). PMID- 2587232 TI - Nucleotide sequences of the Chlamydomonas reinhardtii chloroplast genes for tryptophan and glycine transfer RNAs. PMID- 2587233 TI - Nucleotide sequence of the Cephalosporium acremonium pyr4 gene. PMID- 2587234 TI - Nucleotide sequence of the envelope protein gene of a Malaysian dengue-2 virus isolated from a patient with dengue haemorrhagic fever. PMID- 2587235 TI - The mouse histone H2a.2 gene from chromosome 3. PMID- 2587236 TI - Asp700I, a novel isoschizomer of XmnI from Achromobacter species 700 recognizing 5'-GAANN/NNTTC-3'. PMID- 2587237 TI - Isolation and identification of restriction endonuclease BseAI. PMID- 2587238 TI - Isolation and identification of restriction endonuclease BshFI. PMID- 2587239 TI - Isolation and identification of restriction endonuclease BshGI. PMID- 2587240 TI - Isolation and identification of restriction endonuclease BshKI. PMID- 2587241 TI - Nucleotide sequence of the tzs gene from Pseudomonas solanacearum strain K60. PMID- 2587242 TI - Nucleotide sequence of the envelope protein gene of a Malaysian dengue-2 virus isolated from a patient with dengue fever. PMID- 2587243 TI - Nucleotide sequence of the envelope protein gene of a Malaysian dengue-2 virus isolated from a patient with dengue shock syndrome. PMID- 2587244 TI - Improved double-stranded DNA sequencing using the linear polymerase chain reaction. PMID- 2587245 TI - A simple method for screening of NotI linking clones. PMID- 2587246 TI - A simple method for the preparation of plasmid and chromosomal E. coli DNA. PMID- 2587248 TI - Mechanism of inhibition of adenovirus DNA replication by the acyclic nucleoside triphosphate analogue (S)-HPMPApp: influence of the adenovirus DNA binding protein. AB - The acyclic adenosine analogue (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [S]-HPMPA) is a potent and selective inhibitor of adenovirus (Ad) replication in cell culture. We studied the mechanism of inhibition using a reconstituted in vitro DNA replication system. The diphosphoryl derivative (S)-HPMPApp, but not (S)-HPMPA, inhibited the DNA replication of origin containing fragments strongly. The inhibitory effect was exerted at the level of elongation, while initiation was resistant to the drug. Remarkably, the elongation of short strands was only slightly impaired, while inhibition was maximal upon synthesis of long DNA fragments. (S)-HPMPApp appeared to be competitive with dATP, suggesting that the Ad DNA polymerase is the prime target for the drug. We purified the Ad DNA polymerase in complex to the precursor terminal protein to homogeneity from cells infected with overproducing recombinant vaccinia viruses. Employing gapped DNA or poly(dT).oligo(dA) templates, only a weak inhibition was observed. However, inhibition was strongly enhanced in the presence of the adenovirus DNA binding protein (DBP). We interpret this to mean that the increased processivity of the polymerization reaction in the presence of DBP leads to increased drug sensitivity. PMID- 2587247 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2587249 TI - Preparation of a novel psoralen containing deoxyadenosine building block for the facile solid phase synthesis of psoralen-modified oligonucleotides for a sequence specific crosslink to a given target sequence. AB - 4,5',8-Trimethylpsoralen was attached to the C8-position of deoxyadenosine via a sulfur atom and a five carbon atom linker. The modified deoxyadenosine was then converted to a protected phosphoramidite and used as unusual as a building block for solid phase oligodeoxyribonucleotide synthesis. The efficiency of the photoreaction of a psoralen-modified oligonucleotide to a complementary matrix strand reached more than 90% within a 1 hour irradiation time at a wavelength of 345 nm. PMID- 2587250 TI - Synthesis of N2, N2, 7-trimethylguanosine cap derivatives. AB - Several derivatives of N2,N2-7-trimethylguanosine (m3(2,2,7G)-cap, which was found at the 5' ends of small nuclear RNAs, were synthesized by use of S-phenyl N2,N2,7-trimethylguanosine 5'-phosphorothioate (PhSpm3(2,2,7)G) as a key intermediate. This compound was activated by iodine in the presence of phosphoric acid and diphosphoric acid to give N2,N2,7-trimethylguanosine-5'-diphosphate (ppm3(2,2,7)G) and 5'-triphosphate (ppm3(2,2,7)G), respectively. Similar reactions of PhSpm3(2,2,7)G with ADP and GDP gave capped dinucleoside triphosphates, m3(2,2,7)G5'pppA and m3(2,2,7)G5'pppG, respectively. PMID- 2587251 TI - Ribosome loading, but not protein synthesis, is required for estrogen stabilization of Xenopus laevis vitellogenin mRNA. AB - We have examined the effect of protein synthesis and of ribosome loading on the estrogen-mediated stabilization of hepatic Xenopus laevis vitellogenin mRNA. Removal of estradiol-17 beta from the culture medium, which destabilizes vitellogenin mRNA, does not alter the density of ribosomes on polysomal vitellogenin mRNA, or change the proportion of vitellogenin mRNA associated with the endoplasmic reticulum. Cycloheximide, which inhibits elongation, without changing the density of ribosomes on vitellogenin mRNA, does not block estrogen mediated stabilization. In contrast, 2-(4-methyl-2,6-dinitroanilino)-N methylpropionamide, (MDMP), which inhibits initiation, greatly reduces the density of ribosomes on vitellogenin mRNA, and completely blocks estrogen mediated stabilization. Vitellogenin mRNA in MDMP treated cells is degraded at a rate similar to that seen when untreated cells are transferred from medium containing estrogen to estrogen-free medium. This suggests that a ribosome associated degradative system may not be responsible for vitellogenin mRNA degradation. The failure of estrogen to stabilize vitellogenin mRNA in MDMP treated cells is not due to the release of vitellogenin mRNA from the endoplasmic reticulum. Vitellogenin mRNA in MDMP-treated cells remains associated with the endoplasmic reticulum in small polysomes containing 3-5 ribosomes. These data demonstrate that maintaining a high density of ribosomes on vitellogenin mRNA, but not continuing protein synthesis, is necessary for estrogen-mediated stabilization of vitellogenin mRNA. PMID- 2587252 TI - PCR amplification of DNA microdissected from a single polytene chromosome band: a comparison with conventional microcloning. AB - A novel alternative to microcloning for the production of region specific chromosomal DNA is described. In this method, 'microamplification', single bands are dissected from polytene chromosomes and digested with Sau3A. Oligonucleotide adaptors are ligated to these fragments to provide convenient priming sites for polymerase chain reaction amplification. In this way, as much as 1 microgram of DNA can be amplified from a single band. Probes made from PCR amplified DNA from two such dissections have been used to probe cloned DNA form a 100 kb chromosome walk. Whereas conventional microcloning has generated cloned EcoRI fragments corresponding to 3-4 kb of the walk, the PCR probes cover greater than 90% of this chromosomal region. Thus microamplification is significantly more effective than microcloning in providing probes for establishing chromosomal walks. PMID- 2587253 TI - Vaccinia virus encodes a polypeptide with DNA ligase activity. AB - Vaccinia virus gene SalF 15R potentially encodes a polypeptide of 63 kD which shares 30% amino acid identity with S. pombe and S. cerevisiae DNA ligases. DNA ligase proteins can be identified by incubation with alpha-(32P)ATP, resulting in the formation of a covalent DNA ligase-AMP adduct, an intermediate in the enzyme reaction. A novel radio-labelled polypeptide of approximately 61 kD appears in extracts from vaccinia virus infected cells after incubation with alpha-(32P)ATP. This protein is present throughout infection and is a DNA ligase as the radioactivity is discharged in the presence of either DNA substrate or pyrophosphate. DNA ligase assays show an increase in enzyme activity in cell extracts after vaccinia virus infection. A rabbit antiserum, raised against a bacterial fusion protein of beta-galactosidase and a portion of SalF 15R, immune precipitates polypeptides of 61 and 54 kD from extracts of vaccinia virus infected cells. This antiserum also immune-precipitates the novel DNA ligase-AMP adduct, thus proving that the observed DNA ligase is encoded by SalF 15R. PMID- 2587255 TI - In vitro methylation of CpG-rich islands. AB - CpG islands are distinguishable from the bulk of vertebrate DNA for being unmethylated and CpG-rich. Since CpG doublets are the specific target of eukaryotic DNA methyltransferases, CpG-rich sequences might be expected to be good methyl-accepting substrates in vitro, despite their unmethylated in vivo condition. This was tested using a partially purified DNA-methyltransferase from human placenta and several cloned CpG-rich or CpG-depleted sequences. The efficiency of methylation was found to be proportional to the CpG content for CpG depleted regions, which are representative of the bulk genome. However, methylation was much less efficient for CpG frequencies higher than 1 in 12 nucleotides, reaching only 60% of the expected level. That suggests that the close CpG spacing typical of CpG-islands somehow inhibits mammalian DNA methyltransferase. The implications of these findings on the in vivo pattern of DNA methylation are discussed. PMID- 2587254 TI - H2A.X. a histone isoprotein with a conserved C-terminal sequence, is encoded by a novel mRNA with both DNA replication type and polyA 3' processing signals. AB - A full length cDNA clone that directs the in vitro synthesis of human histone H2A isoprotein H2A.X has been isolated and sequenced. H2A.X contains 142 amino acid residues, 13 more than human H2A.1. The sequence of the first 120 residues of H2A.X is almost identical to that of human H2A.1. The sequence of the carboxy terminal 22 residues of H2A.X is unrelated to any known sequence in vertebrate histone H2A; however, it contains a sequence homologous with those of several lower eukaryotes. This homology centers on the carboxy-terminal tetrapeptide which in H2A.X is SerGlnGluTyr. Homologous sequences are found in H2As of three types of yeasts, in Tetrahymena and Drosophila. Seven of the nine carboxy terminal amino acids of H2A.X are identical with those of S. cerevisiae H2A.1. It is suggested that this H2A carboxy-terminal motif may be present in all eukaryotes. The H2A.X cDNA is 1585 bases long followed by a polyA tail. There are 73 nucleotides in the 5' UTR, 432 in the coding region, and 1080 in the 3' UTR. Even though H2A.X is considered a basal histone, being synthesized in G1 as well as in S-phase, and its mRNA contains polyA addition motifs and a polyA tail, its mRNA also contains the conserved stem-loop and U7 binding sequences involved in the processing and stability of replication type histone mRNAs. Two forms of H2A.X mRNA, consistent with the two sets of processing signals were found in proliferating cell cultures. One, about 1600 bases long, contains polyA; the other, about 575 bases long, lacks polyA. The short form behaves as a replication type histone mRNA, decreasing in amount when cell cultures are incubated with inhibitors of DNA synthesis, while the longer behaves as a basal type histone mRNA. PMID- 2587256 TI - Characterization of the human sex hormone binding globulin (SHBG) gene and demonstration of two transcripts in both liver and testis. AB - A genomic cosmid clone for human sex hormone binding globulin (SHBG), a liver secreted plasma glycoprotein that binds sex steroids, was isolated with a previously characterized liver cDNA as probe. Southern blot analysis of genomic DNA indicated that only one SHBG gene is present in the human haploid genome. A 3.8 Kb Xba I-fragment of the clone containing the entire coding region of SHBG was sequenced. The SHBG gene has 8 exons. The 5'-end preceding the translation start site had no TATA box or CAAT box promoter elements. Screening of a human testis cDNA library resulted in the isolation of two distinct cDNA forms. One cDNA was identical with the previously characterized liver SHBG cDNA, thus suggesting that human SHBG and the androgen binding protein (ABP) produced by Sertoli cells are coded for by the same gene. The second cDNA differed from the first by having exon I exchanged with a completely different sequence and exon VII deleted. An exon coding for the 5'-end of this cDNA was found in the cosmid clone 1.5 kb upstream of the first SHBG exon. Primer extension experiments showed the alternatively spliced transcript corresponding to the second cDNA to be present in both liver and testis. From the primary structure of this putative SHBG-gene-related protein, it may be deduced that it is a protein very different from SHBG and probably without steroid binding activity. PMID- 2587257 TI - Functional analysis of GC element binding and transcription in the hamster dihydrofolate reductase gene promoter. AB - Dihydrofolate reductase (DHFR) gene expression is required for cell growth. The DHFR gene promoter contains several GC elements capable of binding the transcription factor Sp1. In this report we have characterized the effect of protein(s) binding to these sequence elements in the Chinese hamster DHFR promoter on transcription. We have constructed a series of deletions containing from 896 to 103 bp 5' to the start of translation. The protein binding domains have been mapped by DNAse I footprint analysis using HeLa nuclear extract, and the function of the protein-binding elements has been assessed by in vitro transcription and transient CAT expression. Maximal transcription in vitro and CAT expression is obtained with a construct containing 3 GC elements extending to position -184. Removal of GC element binding factor(s), by competition with an oligonucleotide containing an Sp1 binding site, completely abolishes transcription in vitro and significantly diminishes CAT expression. Ten-fold higher molar excess of competitor is required to abolish SV40 early transcription, suggesting that the GC element interactions in the DHFR promoter are different from those in the SV40 early region. Co-transfection of a DHFR CAT construct with an expressor of Sp1 dramatically increased CAT expression in Drosophila cells. PMID- 2587258 TI - Initiation and termination of human U1 RNA transcription requires the concerted action of multiple flanking elements. AB - Sequences in the 5' flanking region of small nuclear RNA (snRNA) genes are responsible for recognition of 3' end signals. Formation of the pre-U1 3' end occurs at the downstream signal closest to the promoter, probably by transcription termination. We have analyzed promoter elements for their participation in formation of the 3' ends of pre-U1 RNA. To do this, a human U1 RNA gene with deletions in individual promoter elements was microinjected into Xenopus laevis oocytes and the resulting RNAs were analyzed by a nuclease S1 protection assay. Each of the promoter elements, except element B (the functional equivalent of a TATA box), was shown to be dispensable for recognition of the snRNA 3' end signal. This latter element was necessary, but not sufficient, for initiation of transcription; so its possible role in termination could not be assessed. Therefore, it is likely that recognition of the 3' end signal is an inherent feature of transcription complexes that initiate at an snRNA promoter. PMID- 2587259 TI - Isolation and characterization of a novel human gene expressed specifically in the cells of hematopoietic lineage. AB - A novel cDNA clone designated as HS1, which show an expression pattern limited to human hematopoietic cells, was isolated. About 2kb mRNA of the clone was accumulated in all the mature and immature lymphoid and myeloid cell lines tested, and two of three erythroblastoid cell lines, but not in any cell lines of non-hematopoietic tissues. The same mRNA was also detected in normal lymphoid and myeloid tissues and peripheral blood lymphocytes, granulocytes and macrophages, but again not in non-hematopoietic tissues. Nucleotide sequence of the HS1 predicts a protein of 486 amino acids (Mr 53,931). N-terminal half of the protein retains unique repeating motifs, each of which shows a significant homology with the helix-turn-helix DNA-binding motif of several proteins reported previously. C terminal half of the protein retains a region conserved between non-receptor tyrosine kinases (src family), phospholipase C(PLC)-148 and the crk oncogene product. A unique feature of HS1 suggests that the protein may be involved in signal transduction and regulation of gene expression. PMID- 2587262 TI - Energetics of the B-H transition in supercoiled DNA carrying d(CT)x.d(AG)x and d(C)n.d(G)n inserts. AB - We have studied the B-H transition in the d(AG)x inserts of varying length under superhelical stress. The new data and previously published results for the d(G)31 insert are treated within a phenomenological model of the B-H transition, making it possible to obtain, for the first time, the energy parameters of the B-H transition in the d(AG)x and d(G)n sequences. PMID- 2587261 TI - Structure and functional expression of a cloned Xenopus thyroid hormone receptor. AB - A clone corresponding to a thyroid hormone receptor was isolated from a Xenopus laevis cDNA library prepared from folliculated oocytes. The cDNA encodes a protein of 418 amino acid residues with a domain structure, including a putative DNA binding region with two zinc fingers, similar to other members of the v-erbA related superfamily of receptors. The encoded protein resembles the TR alpha 1 type receptor of the rat. When expressed in COS cells the protein product binds triiodothyronine with a Kd of 0.12 nM. The receptor mediates thyroid-hormone inducible expression of a reporter gene which includes a thyroid hormone response element in its upstream region. PMID- 2587260 TI - Sequences preceding the minimal promoter of the Xenopus somatic 5S RNA gene increase binding efficiency for transcription factors. AB - Sequences preceding the minimal promoter play a role in the differential expression of the Xenopus somatic and oocyte-type 5S RNA genes. In this report, the somatic sequences between -32 and +37 are shown to increase transcriptional activity in microinjected embryos, yet have little to no effect in microinjected oocyte nuclei. In vitro, these sequences increase activity in whole oocyte S150 extracts, but not in oocyte nuclear extracts. In S150 extracts, these somatic sequences facilitate binding by a commonly required factor(s), other than TFIIIA, which forms a stable complex with the 5S gene. This transcriptional enhancement is also apparent in a reconstituted system using purified TFIIIA and partially purified TFIIIB and TFIIIC. PMID- 2587263 TI - Nucleotide sequence of a 16S rRNA encoding gene from the archaebacterium Methanothrix soehngenii. PMID- 2587264 TI - A new snRNA with a trimethylated cap structure in the slime mold Physarum polycephalum. PMID- 2587265 TI - Nucleotide sequence of human preprocathepsin H, a lysosomal cysteine proteinase. PMID- 2587266 TI - Nucleotide sequence and deduced amino acid sequence of the duck beta-globin gene. PMID- 2587267 TI - Nucleotide sequence of the full length cDNA encoding for human type II procollagen. PMID- 2587268 TI - Sequence of human enteric adenovirus type 41 Tak fiber protein gene. PMID- 2587269 TI - KspI, a novel isoschizomer of SacII from Kluyvera species recognizing 5'-CCGC/GG 3'. PMID- 2587270 TI - Nucleotide sequence of the structural genes for the mitochondrial asp, lys, ser tRNAs from chicken. PMID- 2587271 TI - Sequence of a near-full length cDNA clone for a mRNA of barley induced by fungal infection. PMID- 2587272 TI - Tandemly linked tRNA(Gln), tRNA(Val) and tRNA(Lys) genes in Trypanosoma brucei. PMID- 2587274 TI - Sequence and structure of U5 snRNA from Schizosaccharomyces pombe. PMID- 2587273 TI - The structure of the expressible VH gene from a hybridoma producing monoclonal antibodies against porcine transferrin. PMID- 2587275 TI - The primary structure of rat ribosomal protein S14. PMID- 2587276 TI - Sequence of the Calliphora erythrocephala 3B55 satellite: a sequence which is proportionately replicated and transcribed in germ-line polyploid nuclei. PMID- 2587277 TI - Primary structure of the chloroplast small subunit ribosomal RNA gene from Chlorella vulgaris. PMID- 2587278 TI - Sequence of the Dictyostelium discoideum spore coat gene SP96. PMID- 2587279 TI - Nucleotide sequence of a cDNA that encodes a rice glutelin. PMID- 2587280 TI - A rapid semi-automated microtiter plate method for analysis and sequencing by PCR from bacterial stocks. PMID- 2587281 TI - AspHI, a novel isoschizomer of HgiAI from Achromobacter species H recognizing 5' GWGCW/C-3'. PMID- 2587283 TI - New questions and new answers. PMID- 2587285 TI - The effect of circumvaginal muscle (CVM) exercise. AB - Circumvaginal muscle (CVM) home training based on principles of exercise physiology were tested on 48 healthy reproductive-age women. The effect of CVM exercise with a resistance device in place, CVM exercise without a device, and no exercise with device in place was studied. After random assignment to home training, CVM assessment was carried out prior to and after 6 weeks of CVM training at home. Each subject served as her own control and change scores of the three groups, on CVM variables were subjected to analysis of variance. Peak maximum pressure (PMP) was significantly different for the three groups. F = 4.56, df = 2.45, p = .016. PMP of exercise without a device was significantly different from the no exercise group (Dunett's test). Analysis of measurement error between- and within-subjects showed that the inherent variability between women was approximately four times larger than the measurement error. The results support the prescription of CVM exercise to hypertrophy the CVM, and indicate that further investigation of the large variance found in the pressure data is needed. PMID- 2587284 TI - Effects of age on autonomic cardiovascular responsiveness in healthy men and women. AB - Blood pressure and heart rate responses to the Valsalva maneuver (straining) were used to quantify the effects of age on autonomic cardiovascular responsiveness in 110 healthy men and women, 30 to 76 years. In general, aging was associated with diminished sympathetic responsiveness during strain. In women, however, the predominant age effect was a significant reduction in bradycardic response to systolic blood pressure overshoot following release of strain. When present, age related differences in cardiovascular responses to the Valsalva maneuver were manifest by age 45. These findings are consistent with an age-related diminution of autonomic cardiovascular responsiveness in healthy adults. Moreover, they suggest that interventions to reduce the frequency and intensity of straining may be especially important in older adults in order to minimize health risks associated with rapid, abrupt changes in blood pressure. PMID- 2587286 TI - Effect of backrest on central venous pressure in pediatric cardiac surgery. AB - Following cardiac surgery in children, accurate monitoring of right ventricular function, as reflected by central venous pressure (CVP) or right atrial pressure, is crucial. Positioning the child supine has been considered necessary to achieve an accurate CVP reading. In this study the effect of backrest elevation on CVP readings in children following cardiac surgery was explored. The sample consisted of 40 children, 1 day to 9 years of age, who had undergone cardiac surgery within the previous 72 hours. CVP measurements at 0- and 30-degree backrest elevations were obtained hourly for 8 hours for each child. CVP readings were not significantly altered by the bedrest elevation. These findings suggest children may remain elevated for CVP readings rather than being awakened and repositioned to a 0-degree backrest elevation. For children who have nasogastric feedings, respiratory insufficiency, or increased intracranial pressure, a 30-degree backrest elevation may be maintained for the CVP reading, as well as for the children's safety and comfort. PMID- 2587282 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2587287 TI - A longitudinal analysis of stress process among mothers of infants. AB - A model of stress process among mothers of infants was retested. In that model, stressors (work status or infant difficultness) influence maternal identity through perception of stress. Also, maternal identity may be buffered from stressor effects by health-promotive lifestyle. This model previously received partial support in a one-panel mail survey. The present study reports maternal outcomes from a 6-month follow-up of the original sample. One hundred nineteen (69%) mothers of infants aged 8-20 months participated in the follow-up study. Despite subject attrition, most findings from the original study were replicated in this study. As before, work status and perceived stress each contributed to predicting identity. Health-promotive lifestyle acted directly, not as a buffer, on maternal identity. When extraneous influences were controlled, neither perceived stress nor health-promotive lifestyle was significantly correlated across a 6-month period. PMID- 2587288 TI - Development of a system for monitoring infant state behavior. AB - The concept of infant state refers to patterns of behavior that comprise the sleep-wake cycle. The infant's ability to organize state behavior rhythmically is indicative of central nervous system maturation and predictive of later development. This article describes the development of a noninvasive, computerized infant monitoring system that can be used to categorize the infant's sleep-wake behavior into states. Development of the system occurred in two phases: In the first phase of the study, reliability and validity of the infant monitoring system for recording continuous behavioral and physiological data were assessed. These results were then used in the second phase to develop a rule based computer program to interpret the signal data stored on a micro-diskette and to characterize the infant's state throughout the period of monitoring. The capability of computerized data collection and analysis of infant state behavior has expanded the application of this infant monitoring system. Its use as an investigative tool in clinical research is discussed. PMID- 2587290 TI - Themes of grief. AB - A thematic analysis of 30 narrative accounts of bereavement revealed nine themes that included five core themes in bereavement--being stopped, hurting, missing, holding, and seeking; three meta-themes about bereavement--change, expectations, and inexpressibility; and a contextual theme--personal history. The themes were compared with three theoretical perspectives on bereavement by Freud, Kubler Ross, and one defined as existential-phenomenological. Features of bereavement that are dissimilar or unaddressed by the theoretical perspectives were: (a) the quality of grief's changing character, including "waves" and intense pain which may be triggered years after the death; (b) holding, an individual process of preserving the fact and meaning of the loved one's existence; (c) expectations, both social and personal, as to how the bereaved should be overlaying the experience; and (d) the critical importance of personal history in affecting the quality and meaning of individual bereavement. PMID- 2587289 TI - Effects of aerobic interval training on cancer patients' functional capacity. AB - The effect of a 10-week aerobic interval-training cycle ergometer protocol on the functional capacity (VO2Lmax) of 45 women receiving chemotherapy for treatment of Stage II breast cancer was studied. Subjects were stratified by baseline functional capacity (+/- 1 MET) and randomized to experimental (EX), placebo (PL), and control (CO) groups. EX subjects completed a 10-week, 3 times/week exercise training program; PL subjects participated in 10 weeks of nonaerobic stretching and flexibility exercises; the CO group maintained normal activities. The EX group showed significant, p less than .05, improvement on pre- to posttest VO2Lmax as well as workload and test time compared to the PL and CO groups. The interval-training exercise intervention was effective in improving the functional capacity of Stage II breast cancer patients on adjuvant chemotherapy. PMID- 2587291 TI - Re: NCNR's review process. PMID- 2587293 TI - Reaction to the Diagnosis of Cancer Questionnaire: development and psychometric evaluation. AB - The purpose of this study was to develop a scale to assess the initial reactions of individuals to the diagnosis of cancer. Content validity was built into the Reaction to the Diagnosis of Cancer Questionnaire (RDCQ) through responses supplied by 340 ambulatory cancer patients to the question, "What do you remember of your feelings when first told you had cancer?" Test-retest reliability was .86 at a 3-week interval. Factor analysis on a convenience sample of 441 ambulatory cancer patients confirmed the existence of two separate and distinct dimensions, confronting reactions and distress reactions, to the initial diagnosis of cancer that explained 61% of the variance. Internal consistency for both the total tool (alpha = .896) and the two subscales of the RDCQ (confronting dimension = .82, distress dimension = .91) was high. PMID- 2587292 TI - Predictors of depression among wife caregivers. AB - The relationship of caregiver health, past marital adjustment, and received social support to depression was studied in 78 wives who served as primary caregivers to husbands with irreversible memory impairment. In addition, socioeconomic status and attitudes toward seeking help were investigated. The mean age of the wives was 68 years, and the mean length of time they had been caring for their husbands in the home was 4 years, 10 months. Only caregiver health and attitude toward asking for help were significant, p = .001, predictors of depression and accounted for 27% of the total explained variance. PMID- 2587296 TI - Goldilocks and variability. PMID- 2587294 TI - Testing of an Index of Pulmonary Dysfunction in Multiple Sclerosis. AB - The reliability and validity of an Index of Pulmonary Dysfunction in Multiple Sclerosis (Index) comprised of four readily assessed clinical signs was studied. Forty patients with MS performed pulmonary function testing and underwent clinical evaluation to determine whether or not the Index correctly identified those patients with pulmonary dysfunction. The Index correctly predicted the presence or absence of significant respiratory muscle weakness (defined as Pemax less than 50% of predicted) in 32 (80%) of the subjects. All subjects who had normal expiratory muscle strength (Pemax greater than or equal to 80% of predicted) were correctly classified by the Index; however, not all patients with isolated expiratory muscle weakness were correctly identified. Test-retest reliability, interrater reliability (Spearman rho coefficients of 0.87 and 0.94, respectively), and internal consistency (alpha = .83) of the Index were acceptable. Index scores were not associated with changes in any other PFT results except residual volume, which increased with the severity of respiratory muscle weakness. The Index has acceptable validity and reliability for use in clinical practice to identify those neurological patients with expiratory muscle weakness. PMID- 2587295 TI - Improving response rate to mailed questionnaires. PMID- 2587297 TI - Secondary data analysis: a valuable resource. PMID- 2587298 TI - Re: Use of colons in article titles. PMID- 2587299 TI - Accessing clinical agencies: the do's and don'ts. PMID- 2587301 TI - An unappealing idea. PMID- 2587300 TI - The hell called Leros. PMID- 2587303 TI - Body politic: party time. PMID- 2587302 TI - Rest assured. PMID- 2587304 TI - Side-effects of drugs. Monitoring adverse reactions. PMID- 2587305 TI - Side-effects of drugs. Administering pentamidine. PMID- 2587306 TI - Enrolled nurses--united we stand. PMID- 2587307 TI - Understanding confusion. PMID- 2587308 TI - Management: emptying not closing. PMID- 2587309 TI - AIDS--looking after the children. PMID- 2587310 TI - Code of conduct: taking unfair advantage. PMID- 2587311 TI - Caring for the dying in acute hospitals. AB - In 1983, a small descriptive study looking at the distressing symptoms of 26 terminally ill patients (dying from malignant as well as non-malignant disease) was carried out at two different hospitals before the setting up of a hospital support team. Fifty-two nurses involved in the care of these patients were also interviewed, using a taped, semi-structured interview. Nurses generally found caring for the terminally ill rewarding, but first-year nurse learners found coping with their emotions difficult. The senior nurses would have liked more teaching on pain control and care of relatives. Support of nursing staff was seen to be better in wards where the nursing process was being practised. PMID- 2587313 TI - Pets in the ward--and the guinea-pig came too. PMID- 2587312 TI - Fit for nursing. Three stones lighter, and feeling better. PMID- 2587314 TI - Pets in the ward--till death do us part. PMID- 2587315 TI - To whom it may concern. PMID- 2587316 TI - Flexible pay--heads you win.... PMID- 2587317 TI - Flexible pay--divided we stand. PMID- 2587318 TI - Flexible pay--transparent motives? PMID- 2587319 TI - Flexible pay--you ain't seen nothing yet. PMID- 2587320 TI - The twilight zone. PMID- 2587321 TI - Subarachnoid haemorrhage. PMID- 2587322 TI - Mental health: growth of a specialty. PMID- 2587324 TI - Fit for nursing. A little of what you fancy.... PMID- 2587323 TI - More than skin deep. PMID- 2587325 TI - A primary change-over. PMID- 2587326 TI - Student nurse appraisal. PMID- 2587327 TI - Making sense of ... arterial catheterisation. PMID- 2587328 TI - Enrolled nurses: reluctant recruits. PMID- 2587329 TI - Theatre nursing--going, going, gone? PMID- 2587330 TI - Royal treatment. PMID- 2587331 TI - Theatre nursing--a crucial member of the team. PMID- 2587332 TI - Theatre nursing--care planning. PMID- 2587333 TI - Uppers are downers. PMID- 2587334 TI - A school for normal living. PMID- 2587335 TI - The thin end of the wedge? PMID- 2587336 TI - Falling through the net. PMID- 2587337 TI - Mersey medicine. PMID- 2587338 TI - Whistling in the wind? PMID- 2587339 TI - Safe in a cocoon. PMID- 2587340 TI - Fancy footwork. PMID- 2587341 TI - Systems of life No. 176. Senior systems--41. Falls. PMID- 2587343 TI - Pain and the special care baby unit. PMID- 2587342 TI - Drowning out death. PMID- 2587344 TI - Management: a hole in the black hole theory. PMID- 2587345 TI - A review of infusion pumps. PMID- 2587346 TI - Gaza's grim reality. PMID- 2587347 TI - Combating violence. PMID- 2587348 TI - Conveyor-belt caring? PMID- 2587349 TI - Crying with confidence. PMID- 2587350 TI - Voices raised in unison. PMID- 2587351 TI - Playing safe? PMID- 2587353 TI - Aggression--threatening behaviour. PMID- 2587352 TI - Scepticism is good for you. PMID- 2587354 TI - Aggression--invisible injury. PMID- 2587355 TI - Unrealistic expectations? PMID- 2587357 TI - Minimising discomfort of sick newborns. PMID- 2587358 TI - Enrolled nurses. A private conversion. PMID- 2587356 TI - Rituals in nursing. 'It can't hurt that much!'. PMID- 2587359 TI - AIDS: is the danger exaggerated? PMID- 2587360 TI - Birth cushion trial. PMID- 2587361 TI - Health visitors supplement. PMID- 2587362 TI - Alternative approaches. PMID- 2587363 TI - Something worth fighting for. PMID- 2587364 TI - Tuck into food. PMID- 2587365 TI - Unequal partnerships. PMID- 2587366 TI - Is soap healthy? PMID- 2587367 TI - Taking the lead. PMID- 2587369 TI - It takes two. PMID- 2587368 TI - Dying for attention. PMID- 2587370 TI - COSHH-ing employers. PMID- 2587372 TI - A bark worse than the bite? PMID- 2587371 TI - Natty Norahs. PMID- 2587374 TI - Enrolled nurses. Where do we go from here? PMID- 2587373 TI - Enrolled nurses. We're backing the charter! PMID- 2587375 TI - Death--coping with distress. PMID- 2587376 TI - Death--facing up to mortality. PMID- 2587377 TI - Condoning ill-treatment. PMID- 2587379 TI - A model approach. PMID- 2587380 TI - Rituals in nursing--a day in the ward. PMID- 2587378 TI - Is a mistake misconduct? PMID- 2587381 TI - Fit for nursing. Riding to fitness. PMID- 2587382 TI - Adjusting to amputation. PMID- 2587383 TI - Nurse to Cardboard City. PMID- 2587384 TI - Spotlight on children. PMID- 2587385 TI - Children with AIDS. PMID- 2587386 TI - Positive practice. PMID- 2587387 TI - Breast-feeding and HIV. PMID- 2587388 TI - Caring without prejudice. PMID- 2587389 TI - Ethical issues related to the nurse's role in fertility treatment and counseling for patients with AIDS. AB - Issues relating to treatment of clients with AIDS or HIV infections are not easy to resolve. It is important, however, to understand both sides of the issue prior to determining what actions or policies one might make. The ethical concerns presented here reflected issues related to the principles of autonomy, beneficence, justice, nonmaleficence, and fidelity. However, they are only a few of the possible ethical discussions concerning this debate. Most of the arguments centered on either providing fertility treatment and counseling or denying such treatment to clients with AIDS or who are HIV positive. Both sides of the issue used the principles of beneficence and fidelity as the ethical basis for justification of an action. Autonomy, or the violation thereof, also appeared on both sides of this controversial discussion. It is not known whether the scenario presented could ever occur in reality, but with the anticipated increase in the number of AIDS clients who are heterosexuals, the potential for nurses to face such dilemmas also increases. Nurses need to begin to discuss how they might handle such dilemmas and the reasons why they might respond in a particular manner. One hopes that nurses will continue to base their actions on a sensitive reflection of their moral and ethical values as they attempt to care for clients with AIDS. PMID- 2587391 TI - Organ and tissue transplantation. PMID- 2587390 TI - Organ procurement and transplantation. AB - The path of successful organ transplants has been sown with considerable ethical, legal, social, and moral dilemmas. Some of these dilemmas have been addressed to the public's satisfaction, but many questions are left to be answered. The possibility of prolonging a life through high-technology medicine such as transplantation and through the use of drugs, treatment, and mechanical devices has become an everyday occurrence. However, the need for organs and tissues has created an environment in which hard choices must be made. We must all be involved in the decision-making process, as these are social issues that are presently faced by acquaintances, our friends, and perhaps by our own families. We as individuals must examine our own values as clearly as we examine those of the caregivers, policy makers, social scientists, and ethicists who influence the direction of medical care. We must be ready to ask the important and necessary questions that will guide and enable us to do "the right thing." PMID- 2587392 TI - Liver transplantation. AB - Liver transplantation celebrated its twenty-fifth anniversary in 1988. However, only in the last decade has it been accepted as a viable treatment alternative for patients with end-stage liver disease. There currently are over 70 centers in the United States with liver transplant programs. Over 1500 transplants were performed in 1988, and there were 644 people awaiting suitable liver donors, with an average of 150 to 200 patients added to the list each month. This growth has resulted from many factors, including improved operative techniques and anesthetic management, immunosuppressive therapies, and improvements in donor recovery, which has served to increase the acceptable organs available for transplantation. The future of liver transplantation, however, may be somewhat uncertain. Will the cost of patient care continue to be supported by the economy? The goal of liver transplantation is simple: to provide the patient with a better quality and longer life. The question remains, is this a goal that society will deem financially feasible? PMID- 2587394 TI - Ethics, part II: applications in nursing. PMID- 2587393 TI - The nurse's role in promoting the rights of donor families. AB - The critical care nurse is a vital link in the referral of organ donors and, thus, is the determining factor in the number of patients that will receive organ transplants. The process of referring a potential donor to OPOs should be as convenient as possible. It was the goal of this article to explain the referral process of organ donors and, more important, to communicate the dedication and availability of all OPO staff to the critical care nurse. Donor families have repeatedly stated that having the option of organ donation offered to them at one of their most difficult times helped them take something positive away from their loved one's death. This option can occur only when the critical care nurse is an active participant in the organ procurement process. PMID- 2587395 TI - Community health nurses. Their most significant ethical decision-making problems. AB - Community health staff nurses confront a variety of significant ethical problems in practice that require focused attention in nursing education programs and in community nursing agencies. All community health nurses need to learn to identify ethical problems and to learn a process for resolving these problems that incorporates ethical perspectives. This is particularly critical because nursing colleagues depend on one another for help in dealing with ethical problems in practice. To ignore the ethical problems in community health nursing practice and to neglect to teach the knowledge and skills required to deal with them is to fail to provide nurses with essential skills for providing nursing and health care in community settings. PMID- 2587396 TI - [The frequency and course of fibrotic changes in patients with sarcoidosis]. AB - Basing on observations of 960 patients with pulmonary sarcoidosis the authors found fibrotic changes of pulmonary parenchyma in only a few, the incidence being 3.2. Improvement in radiological examination following steroid therapy was seen in 50%, of respiratory function in 30%. Although both examinations do not fully correlate with each other, they are however supplementary with each other, and should be regarded as important criteria of functional involvement and therapy outcome. PMID- 2587397 TI - [Effect of steroid therapy on pulmonary circulation in pulmonary sarcoidosis]. AB - Effect of 12 month steroid therapy on pulmonary circulation at rest and during exercise was assessed in 24 patients with histologically confirmed stage II and III pulmonary sarcoidosis. Pulmonary hypertension was found in 3 patients before starting therapy. In the remaining 21 pulmonary artery pressure was within normal limits. In 18 of these an abnormal increase of pulmonary arterial pressure during exercise was found. After 12 months of steroid therapy in all except 2 patients radiological regression was observed. In most patients pulmonary function improved. Normal pulmonary arterial pressure was found in 22 patients. An abnormal increase of pulmonary arterial pressure during exercise was seen in 12 patients. No correlation could be demonstrated between radiological evaluation, respiratory function and effect of steroids on pulmonary circulation. PMID- 2587398 TI - [Assessment of pulmonary hemodynamics in patients with idiopathic pulmonary fibrosis]. AB - Pulmonary hemodynamics were assessed in 52 patients with idiopathic pulmonary fibrosis of which 25 were confirmed histopathologically. The study group consisted of 26 males and 26 females, of a mean age of 41 +/- 15 years. Pulmonary function studies revealed restrictive changes and increased elastic recoil. Mean vital capacity was 2.6 +/- 1.2 L, compliance - static 97 +/- 59 ml/cm H2O, dynamic 71 +/- 50 ml/cm H2O. Esophageal pressure was - 8.0 +/- 5.3 mm Hg. Mean pulmonary artery pressure was slightly elevated - 22.6 +/- 8.3 mm Hg. Transmural pulmonary pressure was 31.3 +/- 9.8 mm Hg, cardiac output was 7.6 +/- 3.8 L/min, pulmonary resistance 206 +/- 119 dyn sec cm-5. A mild hypoxemia was observed- PaO2 71.8 +/- 13.3 mm Hg. In part of the study group (27 subjects) the response to exercise was assessed. A mean increase of pulmonary artery pressure from 20.4 +/- 7.2 to 38.0 +/- 14.7 mm Hg and a decrease of PaO2 from 74.2 +/- 11.7 mm Hg to 62.5 +/- 15.3 mm Hg were found. Negative correlation was found between mean artery pulmonary pressure and arterial oxygen partial pressure, vital capacity and one-second forced expiratory volume, and a higher correlation between mean transmural pulmonary pressure and PaO2, VC, FEV1 and Cdyn. PMID- 2587399 TI - [Pulmonary arterial pressure and the effect of short term oxygen therapy on it in patients qualified for home oxygen treatment]. AB - Forty patients with chronic bronchitis and emphysema qualified for domiciliary oxygen treatment according to widely accepted criteria were assessed. Only two patients had normal pulmonary artery pressure. Pulmonary arterial pressure correlated well with oxygen arterial partial pressure. It seems that pulmonary hemodynamic studies are not necessary in patient qualification for domiciliary oxygen therapy. Short oxygen therapy (30 min.) produced only a small decrease of pulmonary artery pressure from 31 +/- 10 to 29 +/- 8 mm Hg. Only in 7 patients was the fall greater than 5 mm Hg. Fall of pressure in pulmonary artery produced by oxygen correlated only with initial pulmonary artery pressure and rose proportionally with increase of pressure. PMID- 2587401 TI - [The pathogenesis of pulmonary sarcoidosis]. PMID- 2587400 TI - [Wegener's granulomatosis with adrenal gland involvement]. AB - A case of Wegener's granulomatosis in a female with characteristic three organ involvement (upper airway, lung, kidneys) is presented. The changes were also seen in the suprarenal glands. This merits attention due to the fact that such a localization was never previously published. Diagnostic problems were caused by pulmonary changes imitating lung metastasis. The patient was treated three years with prednisolone and cyclophosphamide. Complete remission was seen in the lungs and kidneys, and regression of the left suprarenal involvement was observed. PMID- 2587402 TI - [Preliminary evaluation of the diagnostic usefulness of bronchoalveolar lavage (BAL) in selected cases of interstitial lung diseases]. AB - Diagnostic usefulness of BAL was assessed in 25 selected cases of interstitial lung diseases. There were 14 cases of allergic alveolitis, 6 cases of idiopathic pulmonary fibrosis and one case each of sarcoidosis, lymphangiomyomatosis, granulomotosis bronchocentrica, lymphogranulomatosis maligna, alveolitis of unknown etiology. BAL was assessed diagnostically usefull in 77% of the cases. More helpful was medical history which proved to be useful in all cases, and pulmonary function tests which were helpful in 84%. Lung biopsy was diagnostic in 66.6% of the cases, TBLB in 36.5%, while open lung biopsy carried out in 6 patients was diagnostic in 100%. Bronchoalveolar lavage is a useful element of diagnostic evaluation in patients with interstitial lung disorders, it is a safe method and well tolerated by the patients. PMID- 2587404 TI - Fumes from the spleen. PMID- 2587405 TI - So what? Furtively phoning. PMID- 2587403 TI - (Mis)understanding Cleveland: foundational issues and the sexual abuse of children. AB - The Cleveland case led to the widespread condemnation of a new system for the diagnosis, initial treatment, and management of child sexual abuse. The Butler Sloss Report identifies what went wrong as resulting from poor organisational links among agencies and poor interpersonal skills among professionals. Without denying that these faults occurred, this paper claims that what happened in Cleveland did so primarily because those making policy ignored two foundational issues inherent in the problem of child abuse: the status of the child in society and hence the State's justification in intervening on her behalf, and the status of abuse and the abuser and the consequences of their medicalisation. Analysis of these foundational issues suggests what additional steps will need to be taken if we are to deal effectively with sexually abused children and their families. PMID- 2587406 TI - Association between low gynaecological age and preterm birth. AB - Low gynaecological age, defined as conception within 2 completed years of menarche, was examined for its association with preterm birth, using data from a geographically based cohort of over 1700 young primigravidae aged 18 or younger at start of prenatal care. After stratifying by chronological age and controlling for confounding variables, low gynaecological age was associated with almost double the risk of preterm delivery whether estimated from the mother's last menstrual period (adjusted odds ratio (AOR) = 1.77, 95% CI 1.19-2.64) or using the obstetric estimate of gestation (AOR = 2.10, 95% CI 1.36-3.25). Low gynaecological age was also associated with an increase in risk of low birthweight (LBW) (AOR = 1.70, 95% CI 1.01-2.88), but not of small-for gestational-age babies (AOR = 0.94, 95% CI 0.49-1.81). Thus low gynaecological age may be an important addition to assessment systems to detect women at risk of preterm labour and delivery. PMID- 2587407 TI - Postneonatal mortality in south New Zealand: necropsy data review. AB - Three southern New Zealand health districts had a postneonatal mortality rate of 8.1 per 1000 livebirths and a postneonatal sudden infant death syndrome (SIDS) mortality rate of 6.3 per 1000 livebirths for the period 1979-1984. This is one of the highest reported rates of SIDS. The 429 postneonatal deaths occurring during the period were assigned to one of four groups: unpreventable (n = 52), possibly preventable non-SIDS (n = 45), SIDS with minor abnormalities at necropsy or premorbid symptoms (n = 167), and SIDS with no abnormalities at necropsy or documented premorbid symptoms (n = 165). These groups were related to obstetric and perinatal data. For those infants classified as SIDS, the winter peak of deaths was particularly marked if death occurred after 3 months of age. These older SIDS deaths had more minor abnormalities at necropsy, a longer interval between time last seen or heard alive and found dead and more thymic petechiae. PMID- 2587408 TI - Problems in estimating the prevalence of epilepsy in children: the yield from different sources of information. AB - A prevalence study of childhood epilepsy in central Oklahoma allowed a comparison of different sources of case-finding. The percentage of all epilepsy cases identified was lowest (9%) from physicians' office records. Higher rates were obtained from review of emergency room records (40%), hospital inpatient records (45%), electroencephalography (EEG) requisitions (68%) and outpatient clinic records (62%). Nearly one-third of the 1159 epilepsy cases were identified from only one source. EEG requisitions provided most of these cases. Although the percentage of all abstracts from one source that identified cases was lowest for EEG requisitions (43%), these abstracts were prepared with much less effort and time than were abstracts from hospital or clinic records, which had higher levels of efficiency (hospital = 52%, clinic = 73%). Hospital inpatient records identified a disproportionate number of children with newborn seizures, simple partial epilepsy, and partial seizures secondarily generalised, and children with multiple developmental handicaps. Fully 10% of all cases had an episode of status epilepticus and, as might be expected, emergency room and hospital inpatient records preferentially identified them. We conclude that case-finding for epidemiological studies of epilepsy in children in some communities is best done through review of EEG requisitions, supplemented by information from outpatient records. PMID- 2587409 TI - Time-trends in necropsy prevalence and birth prevalence of lung hypoplasia. AB - Congenital lung hypoplasia (LH) has been identified with increasing frequency in perinatal and neonatal necropsy reviews. The available prevalence figures have been derived using various diagnostic criteria in different populations and at various times. We therefore reviewed our experience in 15 years of consecutive early neonatal necropsies using one constant set of diagnostic criteria for LH and looked for a time-trend. We determined the necropsy prevalence (no. of cases of LH/no. of necropsies) and the birth prevalence (no. of cases of LH documented at necropsy per 1000 livebirths for inborn patients, and per 1000 referrals for outborn patients) between 1971 and 1985. We then divided this 15-year period into five consecutive 3-year periods to determine if a time-trend was discernible. Whereas early neonatal mortality for neonatal intensive care unit (NICU) admissions progressively decreased from 11.4% to 4.0% between the first and the last 3-year periods, the number of cases of LH per 3-year period did not vary appreciably. As a result, the prevalence of LH at necropsy showed a slight upward trend with time. The overall prevalence was 18%; it was 13% during the first and 23% during the last 3-year period. We found no time-trend in birth or referral prevalence for this lesion, which averaged 1.1 per 1000 livebirths and 9.8 per 1000 referrals. We conclude that lung hypoplasia appears to be emerging as an increasingly prevalent necropsy finding as a result of a shift in proportionate mortality, with the number of patients dying of other causes (denominator) decreasing, and the number of patients dying with lung hypoplasia remaining constant. PMID- 2587410 TI - Classification of small-for-gestational age births: weight-by-gestation standards of second birth conditional on the size of the first. AB - Percentiles of weight-by-gestational age were constructed for first and second births, based on linked sibship-data from the Medical Birth Registry of Norway. Standards were made for weight-by-gestational age of second births conditional on whether the first birth was small-for-gestational age (SGA) or large-for gestational age (LGA). These standards were compared with the conventional, cross sectional standard of all second births. The relevance of the conditional standards was assessed on the basis of perinatal mortality, using logistic regression analyses. When applying cross-sectional standards of second births, more than 30% of the births following a SGA first birth were classified as SGA, compared with only 1.7% following an LGA first births. The overall risk for a perinatal loss in second births following a SGA first birth was twice that among second births following a LGA first birth. When second births were themselves categorised as SGA or non-SGA using the cross-sectional standards, the mortality among the SGA second births was such that the risk was 4 to 5 times higher following LGA first births compared with SGA first births. When conditional standards were applied to define SGA among second births, the risk relation between the subgroups (defined by classification of first birth) corresponded to the observed overall risk pattern. An unconditional SGA classification conceals important differences between clinically distinct subgroups. PMID- 2587411 TI - Acute abdominal pain and appendicitis in north east Thailand. AB - In a survey of emergency admissions to hospital in rural Thailand, acute appendicitis was the commonest cause of acute abdominal pain. Estimates of the incidence of appendicitis, in two series comprising a total of 356 patients, at 3.2 and 3.7 per 10,000 population per year, were relatively high compared with reports from other warm climate countries. In comparison with 1825 cases in studies sponsored by the Organisation Mondiale de Gastroenterologie (OMGE), Thai patients with acute appendicitis were older, presented late and experienced more complications than those in 14 other countries. In Khon Kaen only 2-3% of the cases were children aged 0-9 years, compared with 9-26% in the OMGE series. In patients admitted to hospital with acute abdominal pain in Thailand, acute appendicitis was diagnosed more often than non-specific abdominal pain. The converse was true in the OMGE series. This may reflect the longer distances travelled to hospital by many patients and delays between onset of symptoms and admission to hospital. Acute appendicitis was the commonest definitive diagnosis in both series. This survey indicates that relatively high rates of acute appendicitis may occur in populations eating traditional diets. The results are consistent with the recently described hypothesis of an infective aetiology and increases in appendicitis rates may be expected in people born since the introduction of improvements in environmental sanitation. Further studies are needed to examine trends in the incidence of appendicitis in populations eating traditional diets with both high and low fibre content and to investigate the significance of changing social and environmental factors. PMID- 2587412 TI - European longitudinal study of pregnancy and childhood (ELSPAC). AB - A prospective geographically based series of population studies has been designed to start in pregnancy and to follow the cohort of births until the age of 7 years. Various centres within Europe are participating in this survey, although there is still time for others to join. The strength of the survey relies on the fact that different correlations in different countries may be useful in ascertaining causal relationships and the major thrust of the research is to assess the impact of psychosocial factors on child health and development. PMID- 2587413 TI - Ectopic pregnancies in women associated with the US armed forces. PMID- 2587414 TI - In vivo conversion of vasopressin after microinjection into limbic brain areas of rats. AB - The nonapeptide [Arg8]vasopressin was rapidly degraded with a half-life of lower than 1 minute after local administration into the hippocampus. During the conversion of vasopressin C-terminal fragments were transiently generated. The profile of these metabolites indicated that they were formed by aminopeptidase activity. The aminopeptidase inhibitor amastatin partially inhibited the conversion of vasopressin. A minor pathway involved cleavages in the C-terminus. The results indicate a predominant involvement of aminopeptidase activity in the in vivo metabolism of exogenous vasopressin in the brain. Since products of this metabolic route have been shown to have potent behavioral activities, the behavioral effects seen after microinjection of vasopressin in the brain may be partially due to generation of vasopressin fragments. PMID- 2587415 TI - Peripheral injection of DNS-RFa, a FMRFa agonist, suppresses morphine-induced analgesia in rats. AB - The present results demonstrate an antagonistic effect of DNS-RFa on morphine induced analgesia in rats. This confirms previous evidence presented by others on the effects of FMRFa-related peptides when applied centrally. Unlike these peptides, however, it is shown here that DNS-RFa is effective upon peripheral injection. The effects of DNS-RFa on morphine-induced analgesia were dose dependent (ED50 = 0.5 mg/kg). DNS-RFa alone (5 mg/kg) did not affect the control level of nociception. Peripheral injection of FMRFa (5 mg/kg) did not affect morphine-induced analgesia. DNS-RFa defines the minimal configuration to activate neuronal FMRFa receptors in the pond snail. The present report suggests also that in vertebrates the Arg-Phe-NH2 sequence is essential and that DNS-RFa readily penetrates the blood-brain barrier. PMID- 2587416 TI - IgG from antiserum against endogenous mammalian FMRF-NH2-related peptides augments morphine- and stress-induced analgesia in mice. AB - Two mammalian FMRF-NH2-like peptides have been isolated from bovine brain; an octapeptide with the structure Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (F-8-F-NH2) and an octadecapeptide, Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala Pro-Gln-Arg-Phe- NH2 (A-18-F-NH2). In the present study determinations were made of the effects of intracerebroventricular administration of IgG prepared from antisera raised against these peptides on nociception and morphine- and immobilization-induced opioid analgesia in mice. Both F-8-F-NH2-IgG and A-18-F NH2-IgG antisera increased nociception (thermal response latency) and significantly augmented morphine- and immobilization-induced analgesia in a naloxone reversible manner, with F-8-F-NH2-IgG antisera having a greater effect than A-18-F-NH2-IgG antisera. These results provide further evidence that mammalian FMRF-NH2-like peptides function as endogenous opiate antagonists and have a role in the mediation of antinociception. PMID- 2587417 TI - Peptide fragments derived from the beta-chain of hemoglobin (hemorphins) are centrally active in vivo. AB - A novel tetrapeptide (hemorphin-4) and pentapeptide (hemorphin-5), derived from the beta-chain of hemoglobin, were synthesized by solid-phase methodology, purified and the amino acid sequences confirmed. The central (ICV) effects of hemorphin-4 and -5 were studied in two models of phasic and tonic nociception, the mouse warm water tail-flick assay and hindpaw formalin assay, respectively. Additionally, two physiological endpoints, central modulation of bladder motility and central effects on intestinal propulsion, were studied in rats and mice, respectively. In the tail-flick assay, both peptides (40-100 nmoles) produced a dose-related naloxone-reversible antinociceptive effect when tested 10 min after peptide administration, with the tetrapeptide being slightly more potent than the pentapeptide. No effect was noted for either peptide using the tonic nociception assay, except at a dose of 150 nmoles for hemorphin-5. Inhibition of gastrointestinal propulsion was also not affected by either peptide. However, both peptides (10-40 nmoles) inhibited micturition contractions in a dose-related and naloxone-reversible fashion, with the tetrapeptide being twice as potent as the pentapeptide. These findings provide evidence that hemorphin-4 and -5 exert naloxone-reversible opioid actions in vivo and, therefore, may be physiologically important blood-borne peptides. PMID- 2587418 TI - Effect of acute exercise on plasma neurotensin levels. AB - Neurotensin (NT) levels were examined in five aerobically untrained females aged 20-36 engaged in acute graded exercise testing. In addition to radioimmunoassay measurements, high pressure liquid chromatography was performed to further characterize plasma NT-like immunoreactivity (NTLI). Epinephrine (E), norepinephrine (NE), and lactate (L) responses were also determined. Exercise testing consisted of one hour of treadmill running subdivided into three 20 minute segments representing 50, 60, and 70%, respectively, of the previously determined maximal aerobic capacity. Mock testing established baseline values for each subject. Three components of NTLI were evaluated: NT(1-13), NT(1-8), and NT(1-11). Resting NT(1-13) concentrations averaged 5.8 +/- 4.2 fmol/ml, while mean NT(1-8) values were 13.0 +/- 5.2 fmol/ml, and NT(1-11) averaged 5.8 +/- 3.2 fmol/ml. Peak exercise values were: for NT(1-13), 5.4 +/- 2.0 fmol/ml, for NT(1 8), 13.5 +/- 2.8 fmol/ml, and for NT(1-11), 5.9 +/- 0.5 fmol/ml. Analysis of variance with repeated measures detected no changes in these levels with exercise. Four-fold increases in E (36 +/- 3 pg/ml to 121 +/- 51 pg/ml), NE (340 +/- 95 pg/ml to 1431 +/- 319 pg/ml), and L (0.8 +/- 0.1 mM to 4.3 +/- 1.7 mM) confirmed the stress of exercise on the body in general, and the sympatho-adrenal system in particular. While other research has associated peripheral NT metabolite elevations with stressful stimuli in laboratory animals, the results of the present study suggest either that NT is not released from the human adrenal medulla during exercise, or that peripheral sampling precludes detection of any increases in NT from the adrenal medulla with currently available radioimmunoassay systems. PMID- 2587419 TI - Melanin concentrating hormone (MCH): structure-function aspects of its melanocyte stimulating hormone-like (MSH-like) activity. AB - Melanin concentrating hormone (MCH) is a heptadecapeptide, Asp-Thr-Met-Arg-Cys Met-Val-Gly-Arg-Val-Tyr-Arg-Pro-Cys-Trp-Glu-Val, synthesized in the brain and secreted from the pars nervosa of teleost fish. This hormone stimulates melanosome (melanin granule) aggregation within integumental melanocytes of fishes but, in contrast, stimulates melanosome dispersion within tetrapod (frog and lizard) melanocytes. We determined the message sequence of the primary structure of MCH which is responsible for its MSH-like component of activity. Removal of the N-terminal amino acid results in an almost total loss of MSH-like activity. The C-terminal amino acid is also essential for full MSH-like activity since the analogue, MCH(1-16), is about 100 times less active than MCH. Therefore, the entire heptadecapeptide sequence of MCH appears to contribute to the MSH-like activity of MCH. Ring-contracted analogues (e.g., [Ala5, Cys10]MCH) of MCH are almost devoid of any melanosome aggregating (MCH-like) activity but generally possess considerable or as great an MSH-like activity as MCH. Racemization of MCH by heat-alkali treatment drastically reduces the MCH-like activity of MCH, but does not enhance the MSH-like activity of the hormone. PMID- 2587420 TI - Inhibitory effect of ceruletide on haloperidol-induced catalepsy in rats. AB - Ceruletide (CLT: 160 micrograms/kg, SC) produced a relatively long-lasting inhibition of haloperidol (HPD: 2 mg/kg, PO) catalepsy in rats. Neither bilateral vagotomies nor hypophysectomy abolished the anticataleptic effect of CLT. However, (-)-L-364,718 and proglumide blocked the effect of CLT. CLT (160 micrograms/kg) significantly inhibited HPD (2 mg/kg)-induced increase in dopamine (DA) release from the rat striatum. This effect of CLT was also antagonized by proglumide. These results suggest that CLT (160 micrograms/kg) primarily acts on cholecystokinin-A receptor in the brain, exerts some modulatory influence on HPD binding to striatal DA receptors via unknown neural pathways and, consequently, inhibits HPD catalepsy. PMID- 2587421 TI - A new molecular form of PYY: structural characterization of human PYY(3-36) and PYY(1-36). AB - A radioimmunoassay was developed using an antibody raised in rabbits against synthetic porcine PYY. This radioimmunoassay was used to detect PYY immunoreactivity in human intestinal extracts. Human colonic mucosa was extracted with acid, centrifuged and the supernatant concentrated by low pressure preparative reverse phase chromatography. A subsequent C-18 reverse phase HPLC step separated two peaks of PYY immunoreactivity. Each peak was purified by sequential steps of ion-exchange FPLC and reverse phase HPLC. In the final purification step single absorbance peaks were associated with PYY immunoreactivity. Microsequence, amino acid, and mass spectral analysis of the intact and tryptic fragments of the two peptides were consistent with the structures: YPIKPEAPGEDASPEELNRYYASLRHYLNLVTRQRY-amide [human PYY(1-36)] and- IKPEAPGEDASPEELNRYYASLRHYLNLVTRQRY-amide [human PYY(3-36)]. Human PYY(1-36) differs from porcine PYY only at position 3, with Ile instead of Ala, and position 18, with Asn instead of Ser. PYY(3-36) may differ in its biological activity from the intact peptide. Its high proportions in the colon suggest that it is released into the circulation where it could act as a partial antagonist of PYY(1-36). PMID- 2587423 TI - Gastrin releasing peptide (GRP) is present in a GRP(1-27) form in anterior pituitary cells of the guinea pig. AB - Immunohistochemical and chromatographic studies were performed on the guinea pig anterior pituitary gland with an antiserum recognizing an epitope within the gastrin releasing peptide (GRP) carboxyterminal amino acid sequence Val-Gly-His Leu-Met-NH2. Within the anterior pituitary gland GRP-like immunoreactive cells were identified. The GRP-like immunoreactive cells were distributed heterogenously in the gland, predominantly located in ventral aspects of the anterior pituitary. Intracellularly, the immunoreactivity elements were identified as granula-like structures in the cytoplasma. To further characterize the peptide displaying GRP-like immunoreactivity within the pituitary cells, the GRP-like substances were analyzed by radioimmunoassay and gel filtration chromatography. Using this analytical approach it was determined that the guinea pig pituitary extract contained a peptide with characteristics similar to that of authentic porcine GRP(1-27). Only trace amounts of smaller C-terminal fragments were identified. These results indicate, in contrast to findings in other tissues, the GRP(1-27) is not further degraded into smaller peptide fragments. PMID- 2587422 TI - Cholecystokinin receptors mediate enhanced memory retention produced by feeding and gastrointestinal peptides. AB - Ingestion of food in mice following training on T-maze footshock avoidance enhanced memory retention when tested 7 days later. This eating-induced improvement of retention was blocked by a specific cholecystokinin antagonist, L 364,718. The cholecystokinin antagonist prevented enhancement of memory retention resulting from posttraining administration of the gastrointestinal hormones, cholecystokinin, bombesin or gastrin releasing peptide. L-364,718 neither impaired or improved retention when given alone. Specificity of the effect of L 364,718 was demonstrated by the failure of L-364,718 to block improved memory retention resulting from administration of arecoline and D-amphetamine. The studies provide evidence that activation of cholecystokinin receptors plays a physiological role in the mediation of meal-induced enhancement of memory retention. PMID- 2587424 TI - Distribution of FMRFamide-like immunoreactivity in the central nervous system of the Formosan monkey (Macaca cyclopsis). AB - The distribution of FMRFamide-like immunoreactivity in the central nervous system of the Formosan monkey (Macaca cyclopsis) was investigated employing immunohistochemical techniques. FMRFamide-containing cells were found to be widely distributed throughout the forebrain. Principal densities of FMRFamide neuronal perikarya were observed in the following areas: the amygdaloid complex, the olfactory tubercle, the cerebral cortex, the basal ganglia, the septum, the caudate-putamen and the arcuate nucleus. A large number of immunoreactive fibers were observed in areas ranging from the cerebral cortex to the spinal cord, and were noted in the following locations: the preoptic area, the tuberal and posterior hypothalamic areas, the bed nucleus of the stria terminalis, the nuclei of the spinal trigeminal nerve, the hypoglossal nucleus, the nucleus of the solitary tract, and the dorsal horn of the spinal cord. The results generally parallel those described in the rat and guinea pig. PMID- 2587425 TI - Aplysia brasiliana neurons R3-R14: primary structure of the myoactive histidine rich basic peptide and its prohormone. AB - Neurons R3-R14 of the marine mollusc Aplysia are model neuroendocrine cells thought to regulate cardiovascular activity in vivo. The cells express a gene encoding three peptides--peptides I, II and the histidine-rich basic peptide (HRBP)--each of which has been chemically characterized in Aplysia californica. In the studies presented here, HRBP and its prohormone (proHRBP) were purified from A. brasiliana abdominal ganglion extracts by reversed-phase high-performance liquid chromatography and characterized by amino acid compositional and sequence analyses. ProHRBP was an 85-residue peptide whose sequence was: NH2-Glu-Glu-Val Phe-Asp-Asp-Thr-Asp-Val-Gly-Asp-Glu-Leu-Thr-Asn-Ala-Leu- Glu-Ser - Val-Leu-Thr Asp-Leu-Lys-Asp-Lys-Arg-Asp-Ala-Glu-Glu-Pro-Ser-Ala-Phe-Met- Thr-Arg - Leu-Arg Arg-Gln-Val-Ala-Gln-Met-His-Ile-Trp-Arg-Ala-Asn-His-Asp-Arg-His- His-Ser - Thr Gly-Ser-Gly-Arg-His-Ser-Arg-Phe-Leu-Thr-Arg-Asn-Arg-Tyr-Gly-Gly-Gly- His-Leu - Ser-Asp-Ala-COOG. It differed from A. californica pro-HRBP at seven of the 85 positions. Compositional and sequence analyses demonstrated that A. brasiliana HRBP was a 43-residue peptide corresponding to residues 43 through 85 of proHRBP, and that a significant proportion of the isolated peptide possessed a blocked NH2 terminus. Although this sequence differed from that of A. californica HRBP at five of 43 residues, the two peptides were approximately equipotent in inducing contractions of A. californica crop muscle in vitro, suggesting that the substituted residues may not be critical for biological activity. PMID- 2587426 TI - Physiological antagonism between prostaglandin E2 and neuropeptide Y on thermoregulation in the dog. AB - These experiments were undertaken to determine whether neuropeptide Y (NPY) could suppress a prostaglandin hyperthermia in conscious dogs. Prostaglandin E2 (PGE2) (5 micrograms), injected into the lateral cerebral ventricle (ILV), evoked a hyperthermia of approximately 1 degrees C. Addition of ILV NPY (5 micrograms) significantly attenuated the PGE2-induced hyperthermia, whereas pancreatic polypeptide (PP), another member of the PP family peptide, did not. These results provide evidence for a role of NPY on thermoregulation in the dog. PMID- 2587427 TI - A-18-famide and F-8-famide, endogenous mammalian equivalents of the molluscan neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH2), inhibit colonic bead expulsion time in mice. AB - Morphine and the two endogenous mammalian FMRFamide (Phe-Met-Arg-Phe-NH2)-related peptides known as morphine-modulating neuropeptides, F-8-Famide (Phe-Leu-Phe-Gln Pro-Gln-Arg-Phe-NH2) and A-18-Famide (Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser Leu-Ala-Ala-Pro-Gln-Arg-Phe -NH2), were administered intracerebroventricularly (ICV) to mice and the effect of each on colonic bead expulsion time was measured. Each of the three compounds delayed expulsion of a 3 mm glass bead placed in the distal colon. A-18-Famide was more potent than F-8-Famide [ED 50 = 2.3 micrograms (1.2 nmole) and 13.9 micrograms (13.0 nmole), respectively]. A-18-Famide: 1) did not block morphine-induced delay of bead expulsion time, and 2) was blocked by simultaneous administration (ICV) of 1.0 microgram of the competitive opiate antagonist naloxone. These data demonstrate apparent opioid modulatory or agonist like, rather than antagonist-like, properties of A-18-Famide and F-8-Famide. PMID- 2587430 TI - Long-term follow-up of the ultraviolet light threshold in guinea pigs photosensitized by 3,3',4',5 tetrachlorosalicylanilide. PMID- 2587429 TI - Testing the efficacy of sunscreens: effect of choice of source and spectral power distribution of ultraviolet radiation, and choice of endpoint. AB - The problems inherent in testing the protective efficacy of sunscreens are reviewed. Of primary importance are: the spectral power distribution of the test light source, which should simulate the ultraviolet radiation of midlatitude, midsummer sunlight; definition of minimal erythema of skin, and equilibration of light source and filters prior to testing. PMID- 2587428 TI - Porcine VIP is more potent than guinea pig VIP in relaxing the guinea pig uterine artery. AB - The vasodilator potency of guinea pig VIP (gp VIP) on the guinea pig uterine artery was compared with the potency of porcine VIP (p VIP), which differs in amino acid sequence at four locations. When antioxidants were not used, the two peptides were approximately equipotent in causing relaxation of precontracted vessel segments. Use of the antioxidants ascorbic acid and dithiothreitol resulted in significantly increased potency of both peptides. Porcine VIP was 15 times more potent than gp VIP synthesized by the same method (tBoc), and gp VIP synthesized by tBoc methodology was 2 times more potent than gp VIP synthesized by Fmoc methodology. Therefore, care should be taken in the choice and handling of synthetic peptides when aiming to mimic actions of endogenous peptides. PMID- 2587431 TI - Effect of 8-methoxypsoralen on granulocytes without ultraviolet irradiation. PMID- 2587432 TI - Is viewing television harmful to actinic reticuloid patients? PMID- 2587433 TI - Positive photopatch tests in polymorphous light eruption. PMID- 2587435 TI - Repeated electroconvulsive shock (ECS) reduces the isoprenaline-induced drinking in rats. AB - The effect of acute and repeated (once daily for 10 days) treatment with ECS on drinking induced by isoprenaline (50 micrograms, intracerebroventricularly, icv) was studied in rats. It was found that repeated, but not acute, administration of ECS significantly reduced the behavioral response to isoprenaline. PMID- 2587434 TI - Interaction between ketamine and ethanol in rats and mice. AB - The development of tolerance to analgesic effects of ethanol and ketamine, development of cross-tolerance between those drugs, and the effects of ketamine on the symptoms of ethanol abstinence were investigated in mice and rats. The analgesic action of ethanol (2.8 g/kg in rats, 5 g/kg in mice) was significantly reduced in the animals chronically treated with ethanol. Chronic treatment with ketamine (100 mg/kg in rats, 160 mg/kg in mice twice daily for 7 days) resulted in development of tolerance to the analgesic effects of ketamine. Cross-tolerance developed to the analgesic action of ketamine in mice and rats receiving ethanol chronically. A chronic treatment with ketamine resulted in development of significant cross-tolerance to the antinociceptive action of ethanol. Ketamine significantly attenuated the symptoms of ethanol abstinence (head shakes) in mice (20 mg/kg) and rats (25 mg/kg). Naloxone pretreatment (2 mg/kg) antagonized the inhibitory action of ketamine on the ethanol abstinence in rats. Doses of 12.5-75 mg/kg of ketamine abolished or significantly inhibited the ethanol abstinence symptoms (audiogenic seizures) in rats. The results demonstrate some similarities of the action of ketamine and ethanol and suggest a possibility that the endogenous opioid system participates in the mechanisms of action of the investigated compounds. PMID- 2587436 TI - The effect of microinjections of clonidine into the locus coeruleus on cortical EEG in rats. AB - Microinjections of clonidine into the locus coeruleus (LC) area synchronized rat cortical EEG. This effect of clonidine was attenuated by local pretreatment of rats with idazoxan, an alpha-2 adrenoceptor antagonist. The data indicate functional role of alpha-2 adrenoceptors within LC area in regulation of ceruleocortical activity, and point at the LC as one of brain targets for the sedative action of clonidine. PMID- 2587437 TI - The central action of 1-(2-pyrimidinyl)-piperazine, an ipsapirone metabolite. AB - The central action of 1-(2-pyrimidinyl)-piperazine (1-PP), a metabolite of ipsapirone, was studied in mice and rats. 1-PP decreased the locomotor activity and slightly increased the body temperature at an ambient temperature of 21 degrees C, not changing it at an ambient temperature of 28 degrees C. The examined substance antagonized clonidine effects (hypothermia, locomotor hypoactivity, stimulation of the hind limb flexor reflex of the spinal rat). Stimulation of the flexor reflex by St 587, an alpha 1-adrenoceptor agonist was not blocked by 1-PP. 1-PP-induced stimulation of the flexor reflex was blocked by cyproheptadine, ketanserin and pirenperone, but not by prazosin or yohimbine. Given in high doses, 1-PP evoked a flat body posture syndrome, but not forepaw treading or head twitches. The obtained results indicate that 1-PP has mainly an alpha 2-adrenolytic action and differs from ipsapirone in its profile. PMID- 2587438 TI - A possible mechanism of tumor regression in cisplatin-treated mice. AB - Immunization of mice with cisplatin results in specific enhancement of host's cellular immune system by stimulating splenocytes and peritoneal exudate cells against the specific tumor antigens. Possible mechanism of tumor cell destruction by splenocytes/PEC was analyzed. Intimate contact between the two cells is the most essential step during the tumor effector cell reaction. PMID- 2587439 TI - Catecholamine levels in the brain and adrenals of rats poisoned with triphenyltin (Brestan 60). AB - The effects of organotin fungicide Brestan 60 and SnCl4 on rat brain and adrenal catecholamines (CA) were examined. Rats were treated with 0.5 LD50 of Brestan 60 (acute experiment) or 0.05 LD50 (subchronic experiment) and SnCl4 in equal dose of inorganic tin. Brestan 60 in both experiments decreased CA concentrations in the brain and adrenals. In contrast, SnCl4 did not alter brain CA but had greater effect on adrenal CA than Brestan 60 had. Effects of organotin fungicide may be related with inhibition of oxidative phosphorylation and membrane-bound ATP-ases. PMID- 2587440 TI - Synthesis and preliminary pharmacological investigation of the central action of derivatives of 3-aminomethyl-5-(p-chlorophenyl)-tetrahydrofuran-2-one and 2 aminomethyl-4-(p-chlorophenyl)-4-hydroxybutyric acid. AB - Using 3-cyano-5-(p-chlorophenyl)-tetrahydrofuran-2-one 4, 3-aminomethyl derivatives of 5-(p-chlorophenyl)-tetrahydrofuran-2-one were synthesized. The starting material under alkaline hydrolysis yielded 5-(p-chlorophenyl) tetrahydrofuran-2-one-3-carboxylic acid 5, which was transformed, via an acid chloride, into amide 6. From acid 5 by aminomethylation compounds 7-12 were obtained. Some of them (7, 8, 12) in reactions of ammono-, amino-, and hydrazinolysis yielded corresponding derivatives of 2-aminomethyl-4-(p chlorophenyl)-4-hydroxybutyric acid 13-20. In pharmacological tests compounds 10 displayed analgesic activity while compounds 2 and 3 revealed anxiolytic properties. PMID- 2587441 TI - Potential antihypertensive benzimidazole derivatives. AB - A series of benzimidazole derivatives was synthesized and tested for their hypotensive activity. The most interesting compounds were: BS1/81 (2-guanidino benzimidazole) and BS1/84 (2-guanidino-5-aminobenzimidazole dihydrochloride), which effects were comparable to those of aminophylline. It was found that substitution of guanidine nitrogen atom with phenyl group caused a distinct decrease of activity while cyclization of guanidine rest to pyrimidine ring caused only a small decrease of activity. PMID- 2587443 TI - Crystalloids in latent prostatic carcinoma. AB - Intraglandular crystalloids have been studied in 108 cases of latent prostatic carcinoma collected at autopsy. The morphological features of these crystalloids are essentially the same as reported by previous authors. The crystalloids were identified in 62.0% of cases over age 50 years. They were present in 76.9% of cases in the seventh decade, the highest prevalence among the decades. The number of crystalloids relative to the number of malignant glands tended to be inversely proportional to the size of the carcinoma. We conclude that crystalloids are related to the early development of prostatic carcinoma. PMID- 2587442 TI - Synthesis and some pharmacological properties of three new analogues of arginine vasopressin modified in positions 1,2,4 and 9. AB - We have synthesized three new analogues of arginine-vasopressin (AVP) to determine some of the structural features that account for antagonistic potency. These analogues are as follows: 4-glutamic acid (gamma-N,N-diethylamide)-8 arginine-vasopressin (I), N,N-diethylamide 1-(1-mercaptocyclohexaneacetic acid)-2 0-methyltyrosine- 4-glutamic acid (gamma-N,N-diethylamide)-8-arginine-vasopressin (II) and 1-(1-mercaptocyclohexaneacetic acid)-2-0-methyltyrosine-4-glutamic acid (gamma-glycine amide)-8-arginine-vasopressin (III). Analogues II and III are weak and moderate antagonists of the vasopressor response to AVP, respectively. Analogue III only exhibits a weak anti-antidiuretic activity. Analogue I lacks antagonistic effects in both systems. PMID- 2587444 TI - Surgical release for exertional compartment syndrome: don't be too hasty. PMID- 2587445 TI - The significance of intracompartmental pressures in the diagnosis of chronic exertional compartment syndrome. AB - Chronic exertional compartment syndrome is one cause of pain in the lower extremity, a common disability in athletes. The significance of intracompartmental pressures in the diagnosis of chronic exertional compartment syndrome is somewhat controversial. The goal of this study was to review the compartment pressure tests in a group of patients that underwent fasciotomy for refractory exertional compartment syndrome and to compare these pressures with an asymptomatic control group. The results are presented and compared with those of previous studies. PMID- 2587446 TI - Complications of the PCA anatomic patella. AB - A retrospective review of the total knee arthroplasties performed using the PCA anatomic patella (Howmedica, Rutherford, NJ) was undertaken after a high rate of complications was noted. Eighty-seven knees in 75 patients were evaluated with an average follow up of 16 months. Eighteen complications of the patella in 14 knees were found (16%); these included lateral subluxation (10 knees), fracture of the patella (5 knees), patellar tendon rupture (2 knees) and prosthetic loosening (1 knee). Seven patients required secondary procedures with the ultimate result greatly compromised in four patients. It is proposed that if the component is not precisely aligned, the eccentric shape and central ridge increases the forces acting at the patella and leads to an increased risk for complications, making the component less forgiving than the more standard dome-shaped patellar component. PMID- 2587447 TI - A physiological comparison of the short-leg walking cast and an ankle-foot orthosis walker following 6 weeks of immobilization. AB - Iatrogenically induced weakness, stiffness, and functional impairment associated with classical methods of short-leg cast immobilization have long been recognized. This study compares the effects of "controlled" immobilization with an ankle-foot orthosis (AFO) and short-leg cast (SLC) immobilization for 6 weeks. A significant reduction in loss of range of motion, muscular strength, and muscular atrophy, ie, functional impairment, at the time of cessation of immobilization was noted when an AFO was used. The additional advantages of an AFO are the elimination of multiple cast changes including economic benefits, ease in the assessment of functional improvement during treatment, and convenient adjustment for swelling and atrophy. PMID- 2587448 TI - Operative technique: a new distal aiming device for locking nail fixation. PMID- 2587449 TI - Radiographic distortion of bones: a marker study. AB - The osseous shadows observed on radiographs are distorted by parallax and magnification error. Parallax may be minimized by proper centering of the subject; magnification error is governed by the subject-to-cassette and exposure distances. The usual assumption that radiographic magnification is 15% is, therefore, erroneous and misleading. A triangular marker was used to assess radiographic distortion of bones on films exposed at "standard" distances of 40 and 72 inches, varying the subject-to-cassette distance to simulate the effect of positioning problems posed by body habitus or joint contracture. Osseous magnification ranged from 6% to 36% on the 40-in exposures and from 3% to 17.5% at 72 in. Using a mid-sagittal marker, true bone size can be more closely determined; once the magnification is known, linear measurements can be normalized for accuracy, permitting valid comparison of quantitative data. Preoperative planning of reconstructive procedures, including implant sizing with templates, is greatly facilitated. PMID- 2587450 TI - Analysis of mechanical factors affecting fixation of olecranon fractures. AB - Fractures of the most distal part of the olecranon process differ from more proximal fractures because a plane of instability exists between the humerus and the radial head. Thus, the fixation of these fractures must resist the deforming forces of the forearm flexor muscles. The investigators fixed 10 paired cadaver ulnae with either the tension-band wire technique or a one-third tubular plate, and tested the specimens to simulate the effect of the biceps and brachialis muscles. The average maximum fixation stiffness for specimens fixed with the one third tubular plate was found to be 163 N/mm compared with 53 N/mm for the tension-band wire group. This study indicates that for fractures of the distal part of the olecranon, fixation with screws and a one-third tubular plate affords better resistance to the forces applied by the brachialis and the biceps brachii than the tension-band wire technique. PMID- 2587451 TI - Reconstruction of the distal radioulnar joint for chronic volar dislocation. A case report. PMID- 2587452 TI - Radiologic case study. Slipped epiphysis associated with renal osteodystrophy. PMID- 2587453 TI - Answer please. Blount's disease: tibia vara. AB - Infantile tibia vara, although uncommon compared to normal physiologic bowing, is significant due to the resultant progressive deformities if not diagnosed early. The key radiographic finding is medial tibial metaphyseal beaking and fragmentation. Although the etiology is unclear, it appears to be an acquired growth disturbance of the proximal medial tibial epiphysis, ossification center, and metaphysis rather than any type of avascular necrosis. The Langenskiold six stage classification is useful for the diagnostic, prognostic, and treatment staging of the disease. The adolescent form is less common and less severe with only slight irregular thickening of the physis present on radiograph. The MDA appears to be the most reproducible method for measuring angular deformities in both variants of the disease. Treatment of the infantile stages I or II consists of observation and bracing. Stage III or IV disease in children over age 3 years with more than 5 degrees of varus angulation should be treated with corrective valgus osteotomy. Stages V or VI may require repeated surgical treatment with multiple osteotomies and possible contralateral epiphysiodesis. The adolescent form frequently requires surgery when there is significant physical impairment related to the severe genu varum. PMID- 2587454 TI - Pediatrician--the Rodney Dangerfield of medicine. PMID- 2587455 TI - Urinary tract infections in infants and children. PMID- 2587456 TI - Jaundice in infancy. AB - Jaundice in infancy may be physiologic or due to a pathologic cause. Fractionation of the serum bilirubin level is the first step in the evaluation. Unconjugated hyperbilirubinemia if left untreated may reach toxic levels. Primary hepatobiliary disorders, as well as infectious, toxic, genetic, and metabolic diseases, may manifest with conjugated hyperbilirubinemia. A carefully organized diagnostic evaluation in a timely fashion allows early identification of treatable disorders. Medical management of the complications of cholestatic liver disease remains a major challenge. Early surgical intervention for biliary atresia and significant advances in hepatic transplantation offer the opportunity for long-term survival for infants with previously fatal liver disorders. PMID- 2587457 TI - Inguinal hernia and the acute scrotum in infants and children. PMID- 2587458 TI - Cecal carcinoma presenting as acute appendicitis. AB - Cancer of the colon disguised as appendicitis occurs more frequently than is generally realized and will probably be seen more often as the elderly population increases. In all patients over 40 years of age presenting with acute appendicitis, further diagnostic testing (ie, double contrast enema or colonoscopy) should be done to rule out occult cancer. PMID- 2587459 TI - Acute diarrhea in adults. Management, with emphasis on oral rehydration therapy. PMID- 2587460 TI - Diagnosis and therapy of acute and chronic diarrhea. AB - Many patients who present with acute or chronic diarrhea do not have an important organic disease. Most have functional diarrhea. The history, clinical examination, and initial laboratory studies should lead to a provisional diagnosis with respect to organic or functional origin and help define whether the disease affects the small or large intestine. Specific studies are then obtained to define organic causes. The most common causes of acute diarrhea are infections and drugs, while the most common causes of chronic diarrhea are inflammatory bowel disease, malabsorption, parasitic infections, carcinoma of the large bowel, and metabolic diseases. Clinicians should remember that patients with functional diarrhea are as prone to other severe disease as the rest of the population and avoid allowing the functional problem to mask other signs. PMID- 2587461 TI - Don't worry, you're happy! PMID- 2587463 TI - Saving a rural hospital. PMID- 2587462 TI - A costly visit. PMID- 2587464 TI - Blood component therapy. New guidelines for avoiding complications. AB - Transfusion medicine is an expanding subspecialty that continues to be reshaped and redefined. The current indications for red blood cell (RBC) transfusion are the presence of tissue hypoxia or a hemoglobin level of less than 7 g/dL. Platelet concentrates should be given prophylactically for severe thrombocytopenia secondary to production defects. In the patient who is in need of an invasive procedure or is bleeding, therapeutic platelet transfusion may be needed if the platelet count is less than 50,000/microL or the bleeding time is twice the upper limit of normal or more. Both RBC and platelet transfusion should be avoided if specific therapy is available for the underlying condition. Transfusion of fresh frozen plasma is indicated for reversal of inherited isolated coagulation factor deficiencies, emergent reversal of the effects of warfarin sodium (Coumadin, Panwarfin, Sofarin), antithrombin III deficiency, and thrombotic thrombocytopenic purpura. No blood transfusion is without risk to the recipient. Two of the major transfusion-related complications are alloimmunization and graft-versus-host disease. Techniques for preventing these conditions are available. PMID- 2587465 TI - Managing smoke inhalation injuries. AB - Inhalation injuries most often occur with cutaneous burns, and the likelihood of an inhalation injury increases incrementally with age of the patient and size of the burn. Damage to the pulmonary parenchymal tissue manifests as increased capillary permeability leading to excessive lung fluid formation and increasing hypoxia. An inhalation injury may be diagnosed using observation of indirect criteria in conjunction with fiberoptic bronchoscopy, xenon 133 radiospirometry, and/or measurement of extravascular lung water. Initially, carbon monoxide poisoning threatens the patient's oxygenation capacity. High-flow oxygen therapy reduces the half-life of carbon monoxide to an acceptable period. The patient proceeds through three stages: pulmonary insufficiency, pulmonary edema, and bronchopneumonia. Treatment is directed toward supporting oxygenation using endotracheal intubation with mechanical ventilation, humidification of inspired air, early mobilization, chest physiotherapy, antibiotics for documented infection, and adequate systemic hydration. PMID- 2587466 TI - Diagnosis of acute stroke. How to relate presentation to vascular anatomy. AB - Stroke is a heterogeneous disease with many different causes and presentations. Ischemic strokes can be due to occlusion of large or small vessels by thrombi or emboli. Hemorrhagic strokes are due to rupture of small vessels within the brain or rupture of aneurysms at the base of the brain. An understanding of the vascular anatomy of stroke syndromes is essential to planning an efficient evaluation. The workup should be individualized for each patient and should rule out processes that can produce strokelike syndromes. Despite the availability of advanced imaging tools, the clinical evaluation is still of paramount importance. PMID- 2587467 TI - Effect of eumelanic phenotypes on the expression of amelanosis in the Smyth chicken. AB - The Smyth line is characterized by an autoimmune loss of melanin in the feather and eye in association with a hypermelanizing melanocyte, which presumably triggers immune system intervention. Inheritance appears to be multigenic. The present study was designed to determine if eumelanin-enhancing modifiers influence the incidence and severity of the line-associated amelanosis. Smyth chicks with dark brown (eb) down had a higher incidence of amelanosis (P less than .01) than did their hatchmates with light brown down. Furthermore, parents with dark down at hatch produced a higher incidence of amelanotic progeny than parents with light down. Reciprocal crosses of the Smyth line to a highly eumelanized (eb/eb) Recessive Black (RB) line produced F1 amelanosis. However, sires from the Smyth line produced significantly more amelanotics than did RB males (P less than .01). The influence of dark down on amelanotic development was also apparent in the Smyth-RBF1. The use of amelanotic F1 parents produced a significantly higher incidence of affected F2 offspring than did the use of unaffected parents. A backcross to the Smyth line produced an incidence of 67.6% amelanosis, whereas only one chick (2.04%) developed amelanosis from an F1 x RB mating. The finding that dark-downed Smyth chicks exhibit, and subsequently produce, a significantly higher incidence of amelanosis supports ultrastructural observations that associate the Smyth line amelanosis with a hyperactive melanocyte. The unusually high expression of amelanosis (22.7%) in the Smyth-RB F1 suggests that the two lines share one or more common eumelanogenic genetic factors. PMID- 2587468 TI - Laying performance and fear response of White Leghorns as influenced by floor space allowance and group size. AB - Three experiments were conducted with White Leghorn pullets housed in litter floored pens to determine the effects of floor space allowance and group size on laying performance and fear response. In Experiment 1, 17 birds were housed at a floor space allowance of .40 or .29 m2/bird. In Experiment 2, 22 or 16 birds were housed at a floor space allowance of .31 m2/bird. The following treatments were used in Experiment 3:1) 26 birds per pen at .19m2/bird, 2) 36 birds per pen at .19 m2/bird, and 3) 26 birds per pen at .26 m2/bird. The test period was from 20 to 52 wk of age in each experiment. Duration of the induced tonic immobility, measured at 52 wk of age, was used as a criterion of fearfulness. Decreasing floor space allowance per bird, increasing group size per pen or a combination of the two had no significant effect on final body weight, hen-day egg production, feed efficiency, egg weight, albumen height, or fearfulness of the bird. Decreasing floor space per bird while holding the number of birds per pen constant significantly (P less than .05) increased mortality. Birds given less floor space consumed significantly (P less than .05) more feed than birds given more floor space in Experiment 1. This study indicates that the birds' hen-day egg production, feed efficiency, and fearfulness are not significantly (P greater than .05) influenced by floor space allowance or group size and that effects of floor space allowance and those of group size are not additive. PMID- 2587469 TI - Prelay light restriction of turkey hens: daylength versus exposure time. AB - A 3 x 3 factorial experimental design was used to examine the relationship between the duration of short daylength (10, 8, or 4 h light/day) during prelay light restriction and the length of time (12, 8, or 6 wk) that young turkey hens were exposed to light restriction and subsequent photoinduced reproductive performance. Data were collected for time to first egg, egg production, percentage of fertility, and hatchability, and poult weight. Light restrictions consisting of 10, 8, or 4 h light/day were equally effective in terminating photorefractoriness and preparing hens for subsequent photoinduced reproductive performance. A 6-wk exposure to light restriction did not prepare hens for egg laying as effectively as 8 (P less than .05) or 12 (P less than .10) wk of exposure, both of which were similarly effective. A lack of interaction between the light restriction daylength and exposure time suggests that the requirements for effective light restriction are rather specific and cannot be beneficially manipulated by various combinations of daylength and weeks of exposure. PMID- 2587470 TI - Standard errors of nitrogen-corrected true metabolizable energy estimates: effects of pooling excreta samples and ignoring among-control bird variation. AB - To estimate TME(n), it appears to be advantageous to pool excreta samples prior to analysis for energy and nitrogen; accurate (nonbiased) estimates should result. With this protocol, estimates of precision are based entirely on the among-bird variance in excreta weight of the fed birds. However, because of the inconsistent relationship between excreta weight and excreta energy, the SE resulting from this pooling protocol generally are unrelated to the correct values obtained when the energy and nitrogen concentrations are measured in the excreta of each bird. Failure to account for the among-control-bird variation in excreta energy overstates the precision (i.e. underestimates the SE) of TME(n) estimates. PMID- 2587471 TI - Bioavailability of manganese from feed grade manganese oxides for broiler chicks. AB - An experiment was conducted to study the relative biological availability of Mn from inorganic Mn sources using 288, 1-day-old male Cobb feather-sexed chicks. Chicks were fed a basal corn-soybean meal diet (82.5 ppm Mn, as-fed basis) ad libitum or the basal diet supplemented with 0, 1,000, 2,000, or 3,000 ppm Mn from reagent grade (RG) MnSO4.H2O, MnO RG, or feed grade (FG) Oxide A, B, or C for 21 days. Bone and kidney Mn concentrations were used to estimate bioavailability. Manganese source and level had no effect on chick performance. Uptake of dietary Mn by bone and kidney from all sources was highly linear (P less than .001). Based on multiple linear regression slopes from bone Mn concentrations, the relative bioavailability values of MnO RG and MnO FG A, B, and C were 81.9 +/- 6.0, 93.1 +/- 6.7, 75.0 +/- 3.6, and 70.3 +/- 5.7, respectively, compared with 100% for MnSO4; those based on kidney Mn were 85.7 +/- 7.9, 68.0 +/- 7.5, 52.2 +/ 4.2, and 53.0 +/- 7.3, respectively. PMID- 2587472 TI - Barley and full-fat canola seed in broiler diets. AB - Barley and full-fat canola seed (FFCS), with or without an added enzyme mixture, were evaluated in experiments with broiler chicks. In Experiment 1, test diets contained barley, wheat, and soybean meal and were supplemented or unsupplemented with raw FFCS (10%) or canola meal (6%). The control was a wheat-soybean meal diet. Diets were fed to male and female broiler chicks for 7 wk. The diet supplemented with raw FFCS produced significantly (P less than .05) lower weight gains than the other diets. There were elevated levels (P less than .05) of linoleic and linolenic acids (18:2 omega 6; 18:3 omega 3) in tissue lipids of chicks fed raw FFCS. In Experiment 2, broiler chicks were fed diets containing a steam-pelleted barley-FFCS mixture (80:20), included at a 50% level, along with supplemental barley. Total barley level in the experimental diets was 50%. 45%, and 40%. A barley-soybean meal diet was used as a control. All diets were fed with and without an enzyme supplement. Chicks fed the barley-FFCS diets were similar to those fed the control diet in respect to production parameters and carcass characteristics. Supplementation of diets with the enzyme mixture resulted in significantly larger body weight gains and lower feed:gain ratios. In Experiment 3, enzyme supplementation increased (P less than .01) the ME of the steam-pelleted barley-FFCS mixtures and the mixed feed containing barley-FFCS. Data from Experiment 4 indicated that there were no significant differences in availability among amino acids from barley, FFCS, or pelleted barley-FFCS mixture diets. PMID- 2587473 TI - Effects of antithyroid drug on the rectal temperature and metabolic parameters of ducks (Cairina moschata). AB - The effect of propylthiouracil oral treatment (400 mg/day per bird for 20 days) on body and thyroid weight, rectal temperature and plasma metabolic parameters of ducks (Cairina moschata) was determined. Propylthiouracil treatment produced a reduction (P less than .01) in body weight and an increase (P less than .01) in thyroid weight. The antithyroid drug also produced a decrease in rectal temperature starting from the 15th day of treatment, but did not significantly change blood glucose. Plasma free fatty acids and cholesterol concentrations progressively increased from the 5th and 10th day, respectively, in treated animals. PMID- 2587474 TI - Male broiler performance during the starting and growing periods as affected by dietary protein, essential amino acids, and potassium levels. AB - Three experiments were conducted to determine the effects of dietary CP, essential amino acid (EAA), and K content upon male broiler performance during starting and growing periods (7 to 21 and 21 to 42 days, respectively). In Experiment 1, five grower diets formulated to be equal in K content and containing the following analyzed CP contents were used: 21.9, 19.1, and 16.2% with and without L-glutamic acid (GLU) supplementation or 10% increased levels of arginine (ARG), threonine (THR), isoleucine (ILE), and tryptophan (TRP). Seven diets containing the following analyzed CP contents were fed in Experiment 2: 21.5%, 19.6% with and without K supplementation, and 16.0% with and without K supplementation and/or 10% increased levels of ARG, THR, ILE, and TRP. In Experiment 3, four starter diets containing the following CP contents were fed: 24.5%, and 17.8% without and with added K. In all three experiments feed efficiency (FE) was lower and in Experiments 1 and 2, abdominal fat deposition (AFD) was higher with lower levels of dietary CP. Lower body weight gains (BWG) occurred with lower levels of dietary CP in Experiments 2 and 3, but not in Experiment 1. Adding extra ARG, THR, ILE, and TRP to the lowest CP diet sometimes improved FE, but had no effect on BWG or AFD. Supplementation with GLU or K failed to influence BWG or FE. However, addition of GLU was associated with lower AFD. Maximal performance generally was not obtained with the low CP, amino acid fortified diets. PMID- 2587475 TI - Effect of dietary thyroxine on growth and muscle protein metabolism in broiler chickens. AB - The effects of thyroxine (T4) on growth, feed efficiency, breast muscle (Musculus pectoralis profundus) weight, liver weight, abdominal fat content, and rates of muscle protein synthesis (Ks) and breakdown (Kd) estimated by N tau methylhistidine excretion were investigated in broiler chickens of both sexes. Dietary inclusion of .4 ppm T4 resulted in a less abdominal fat content in female chickens and a higher muscle protein synthesis rate in male chickens. Administration of T4 at the level of 1.2 ppm produced higher feed efficiency in both sexes and greater muscle weight and muscle protein synthesis rate in male chickens. This treatment also produced less abdominal fat content in female chickens. Administration of T4 at the level of 3.6 ppm produced lower body weight gain, breast muscle weight, liver weight, and abdominal fat content in both sexes and both higher protein synthesis and breakdown in skeletal muscle in male chickens. These experiments demonstrated that the abdominal fat content could be successfully reduced by dietary inclusion of T4, especially in female broiler chickens. The findings in the present investigation suggested that the improved feed efficiency and muscle growth were largely accomplished by the increase in muscle protein synthesis induced by the dietary inclusion of thyroxine. PMID- 2587476 TI - Turkey plasma thyroid hormone and prolactin concentrations throughout an egg laying cycle and in relation to photorefractoriness. AB - Plasma concentrations of thyroxine (T4), triiodothyronine (T3), and prolactin were determined weekly through an egg laying cycle induced with 30 wk of 14 h light:10 h dark. Egg production, primary remige molting, and occurrence of photorefractoriness were monitored. Hens were assigned to one of two groups; those that exhibited photorefractoriness (PR) and those that remained photosensitive (PS). Weekly plasma T4 concentrations relative to the time of initiation of photostimulation did not differ between PR and PS groups; concentrations peaked prior to the onset of egg production, were lowest during peak egg production, and increased between Weeks 6 and 30 of photostimulation. Plasma T4 levels of PR hens peaked 3 wk prior to the onset of photorefractoriness. Plasma T3 concentrations of PS and PR hens were similar until increases occurred in PR hens at the onset of photorefractoriness. Plasma prolactin levels in PS and PR hens increased after photostimulation, declined sooner in PR hens, and were generally greater in PS than PR hens during the last 20 wk of the study. Mean time of onset of photorefractoriness in PR hens was 23.0 wk (range = 18 to 28 wk) after initiation of photostimulation. Egg production of PS hens was greater than that of PR hens after 20 wk of photostimulation, and PR hens molted a greater number of primary remiges than PS hens. Results indicated that 1) elevated plasma T4 may be involved in development of photorefractoriness in turkey hens, 2) increases in plasma T3 may be involved in gonadal regression and molting, and 3) elevated plasma prolactin was associated with persistence of photosensitivity. PMID- 2587477 TI - Chick mortality in bobwhite quail as affected by supplemental ascorbic acid. AB - In two experiments, bobwhite quail chicks were given 0, 50, or 500 ppm ascorbic acid (AA) in the drinking water from 1 to 7 days of age. Both levels of AA significantly decreased mortality for the first 7 days and for the 3-wk average. Feed conversion during the entire 3-wk study was improved by 500 ppm AA. Body weight was not affected by AA supplementation. PMID- 2587478 TI - The ethics of NHS prescribing for private patients. PMID- 2587479 TI - Patient participation in appointing a new GP. PMID- 2587480 TI - A case of neuromyelitis optica (Devic's disease). PMID- 2587481 TI - Refractory pseudo-scabies. PMID- 2587482 TI - GP obstetrics: making the most of shared care. AB - The great majority of pregnant women today receive maternity care shared between their GP and specialist obstetric units in district hospitals. This style of care can be rationalised to utilise to the full the skills of the primary care team and thus relieve pressure on often overcrowded hospital clinics. PMID- 2587483 TI - Cough with green sputum. AB - Good treatment often involves advice on lifestyle modification which may be more important in the long run than pharmacological intervention alone. Compliance, however, is always a problem. Some patients refuse to take responsibility for their own health but repeatedly present to the GP to be patched up. The persistent smoker with recurrent bronchitis is just such a patient, but what can the conscientious GP do? PMID- 2587484 TI - Opportunistic screening for hypertension. AB - Opportunistic screening in hypertensive patients aged between 35 and 70 years is a part of good primary medical care. It can be done with very little time added to a routine consultation. More than 75 per cent of patients in each practice could be screened at least once in five years. Preventive medicine could be carried out as well, such as advice on diet, exercise habits, vaccination and cervical smears. PMID- 2587485 TI - A greater role for systolic pressure? AB - The large intervention trials on the treatment of hypertension have been based on the diastolic component of blood pressure. Recent work indicates that elevation of the systolic pressure is just as powerful in predicting stroke and heart attacks. The incidence of systolic-only hypertension in the elderly is between 5 and 20 per cent. How to approach the management of these patients is the subject of current research in the United States. PMID- 2587486 TI - The consultation. PMID- 2587487 TI - Cystic fibrosis. AB - This article outlines the clinical features and investigation of cystic fibrosis. The need for a multidisciplinary approach in specialist centres is highlighted. Future developments, particularly heart lung transplantation and research into the underlying genetic and biochemical abnormality, are discussed. PMID- 2587488 TI - Smoking cessation workshops for GPs. AB - The prevention of smoking has been identified by the World Health Organisation as the most potentially effective preventive health measure that developed countries can take. The role of the GP in this process is crucial. A three-hour smoking cessation workshop attempts to improve counselling skills and includes a suggested role for the GP and a smoking withdrawal protocol. PMID- 2587489 TI - New delivery systems for asthma drugs. AB - The therapy of asthma requires great attention to detail by both doctor and patient since the technique of drug administration always needs care. New developments in drug delivery systems for asthma may make this task easier and lead to reduced morbidity. PMID- 2587490 TI - Clinical assessment of a new breath-actuated inhaler. AB - Up to 50 per cent of patients cannot use a conventional metered-dose inhaler (MDI) efficiently and therefore obtain less than optimum benefit. Seventy adults with no previous experience of inhalers were asked to demonstrate their inhaler techniques after reading written instructions for an MDI and for a new breath actuated inhaler. The breath-actuated inhaler was found to be easier to use and was preferred to the MDI. PMID- 2587491 TI - Tinea incognito. PMID- 2587492 TI - Grief and how to manage it. PMID- 2587493 TI - AIDS--a zero-risk message. PMID- 2587495 TI - Verrucae. AB - Anxiety about minor conditions such as plantar warts can create undue pressure on the GP for cure at all costs. Possibly the true basis of the problem- misinformation at school--lies beyond the practitioner's sphere of action. How to approach the problem as it appears in the surgery is the subject of this discussion. PMID- 2587494 TI - Domino scheme--a GP's view. PMID- 2587497 TI - Tic douloureux--a patient's diary. AB - Tic douloureux is a chronic disease characterised by paroxysmal facial pain. This seven-year account of a patient's symptoms and management is discussed with reference to the medical and surgical treatments now available. PMID- 2587496 TI - Pseudofolliculitis barbae. AB - Pseudofolliculitis and acne keloidales are common skin conditions which are difficult to control and may cause considerable problems for the patient, resulting in disfiguring scarring. In a limited open study, 1% clindamycin was found to be a simple and effective treatment for both conditions. PMID- 2587498 TI - Rheumatism and the menopause. AB - Rheumatic problems at or around the menopause include arthralgia and general rheumatic pains, aggravation or first appearance of rheumatoid or osteoarthritis, backache and carpal tunnel syndrome caused by fluid retention. This article looks at such menopausal conditions and describes how to diagnose and manage them. PMID- 2587499 TI - An analysis of 300 EEG referrals. AB - Although the EEG suffers from limited diagnostic significance it is a useful adjuvant to diagnosis and demands for the examination are increasing. Three hundred consecutive referrals to one unit are analysed. PMID- 2587500 TI - Social medicine. PMID- 2587501 TI - Cystic swelling. AB - Photographing small lesions at high magnification can make it difficult for the reader to orientate to the exact location. This issue's photograph shows all the clinical aspects of a cystic swelling on the patient's digit. PMID- 2587502 TI - Rehabilitation after a myocardial infarction. AB - Myocardial infarction is only one event in a chronic and progressive disease. A well-planned convalescence is part of the long-term promotion of a healthy and enjoyable lifestyle and provides the best possible prognosis. PMID- 2587503 TI - Heartbeat Wales--a community programme. AB - Heartbeat Wales is a broadly based initiative designed to decrease the incidence of cardiovascular disease. After three years there are encouraging signs that the people of the Principality are adopting a healthier lifestyle. PMID- 2587504 TI - Ambulatory monitoring. AB - Electromagnetic recording of intermittent physiological events has enabled physicians to make a diagnosis when physical examination and routine 'tests' are entirely normal. This technique has been most widely used by cardiologists but has other applications. PMID- 2587505 TI - Non-cardiac chest pain. AB - Psychiatric illness is present in up to 50 per cent of new patients attending a cardiac clinic with chest pain. This article provides guidance on the positive diagnostic features of such illness. PMID- 2587506 TI - In vitro effect of organic and inorganic mercury on the serotonergic system. AB - Interactions of organic (methyl mercury) and mineral (acetate, chloride, nitrate: Hg2+) mercury salts with the serotonergic systems were studied in vitro using synaptosomal fractions prepared from rat brain cortex preloaded with [3H]5-HT. In the absence of calcium, mercury salts induced a spontaneous release of the amine corresponding to a total depletion of the synaptosomal content. EC50 for the organic and mineral forms of the ion were 66 +/- 2 microM and 107 +/- 16 microM respectively. In the presence of calcium (2.4 mM) a similar pattern of release was observed except that an additional release was induced by mineral mercury at low concentration (EC50 = 8.4 +/- 1.3 microM) which corresponded to a maximal release of 18.6 +/- 3.5% of the synaptosomal content. Therefore, the latter release appears calcium-dependent. Parallelly, the effects of mercury salts have been examined on the binding of [3H]5-HT to its high affinity 5-HT1 sites; organic and mineral mercury inhibited the binding with IC50 of 27.8 +/- 3.2 microM respectively. These results show that mercury ions interact with the serotonergic system by different mechanisms depending on their concentrations and their ionic forms. PMID- 2587507 TI - Effect of diuretics on adrenergic receptors in the rat. AB - Diuretics have been reported to alter arteriolar smooth muscle responses to adrenergic stimulation as well as lymphocyte beta-adrenoceptor density. We have investigated the effect of four days treatment with hydrochlorothiazide or furosemide (10 mg/kg and day) injected subcutaneously in the rat on alpha 1 ,alpha 2- and beta-adrenoceptors in different tissues. alpha 1-Adrenoceptor density and affinity in whole kidney and heart ventricle as determined by 3H prazosin binding (in the absence and presence of 10(-5) M phentolamine) were unaltered by diuretic treatment, as were beta-adrenoceptor density and affinity in whole kidney, heart ventricle and skeletal muscle as determined by 125I iodocyanopindolol binding (in the absence and presence of 10(-7) M (-) propranolol). The density of alpha 2-adrenoceptors in particulate fraction from whole kidney homogenate as determined by 3H-rauwolscine binding was 12.8% higher in the hydrochlorothiazide-treated group (P less than 0.05) and 15.0% higher in the furosemide-treated group (P less than 0.01) than in the control group. The receptor affinity was similar in the different groups. Thus diuretic-induced alterations in adrenoceptors reported in previous studies were not observed in this study. PMID- 2587508 TI - Fatty acid oxidation in hepatic peroxisomes and mitochondria after treatment of rats with di(2-ethylhexyl)phthalate. AB - Rats were fed a diet containing di(2-ethylhexyl)-phthalate, which increases the number of peroxisomes and mitochondria in the liver. This proliferation does not change the ratio of phospholipid to protein in mitochondria or microsomes, but causes certain changes in the fatty acid composition of the phospholipids. The highest rates of peroxisomal and mitochondrial beta-oxidation are obtained with 12:0 and 16:0 fatty acids as substrates, respectively. A 3-4 fold increase in the rate of beta-oxidation by both organelles is caused by DEHP treatment, but there are no qualitative changes in the relative rates of oxidation of individual fatty acids. Short- and medium-chain carnitine acyltransferases in peroxisomes, microsomes and mitochondria, as well as the mitochondrial long-chain carnitine acyltransferase are induced to various extents. These results indicate that the increased beta-oxidation of fatty acids caused by phthalate treatment involves the same peroxisomal and mitochondrial pathways which operate under normal conditions. PMID- 2587509 TI - Change in small intestinal brush border membranes of rats following methotrexate administration. AB - Change in small intestinal brush border membranes of rats following methotrexate administration was monitored by the fluorescence spectra and polarization of the cationic fluorescent probe, safranin 0. Total protein content of brush border membranes of treated rats was less than that of control rats, whereas no significant difference in total sialic acid content of brush border membranes was observed between them. Thus, an apparent increase in the electronegative charge of brush border membrane vesicles per unit of membrane protein following methotrexate administration may possibly cause the change in fluorescence spectra and polarization of safranin 0. PMID- 2587510 TI - Stimulation by oestradiol of the urinary excretion of perfluorooctanoic acid in the male rat. AB - The urinary excretion of perfluorooctanoic acid (PFOA) was studied in male Wistar rats after castration and oestradiol administration as well as in intact females and males. During the first 24 hr females excreted 72 +/- 5% (N = 6) of a single intraperitoneal dose of PFOA (50 mg/kg) in urine whereas the intact males excreted only 9 +/- 4% (N = 6). After castration followed by oestradiol administration (500 micrograms/kg every 2nd day for 14 days), the males excreted PFOA in urine in similar amounts as the females (68 +/- 14% at 24 hr, N = 10). Oestradiol treatment of non-castrated males produced similar results (61 +/- 19% at 24 hr, N = 10). Also castration without oestradiol administration significantly enhanced the renal PFOA excretion, but not as effectively as oestradiol treatment. After 96 hr, the concentration of PFOA in serum of intact males was 17-40 times higher than in the serum of other groups. PFOA was similarly bound by the proteins in the serum of females and males. Phase II metabolism of PFOA was not shown either in males or females. PMID- 2587511 TI - Covalent binding of four DDD isomers in the mouse lung: lack of structure specificity. AB - Previous studies have shown that o,p'-DDD is activated and covalently bound in the mouse lung. In order to examine the structure dependency of the selective lung binding, the 14C-labelled DDD isomers p,p'-DDD, m,p'-DDD and o,m'-DDD were injected intravenously into female C57B1 mice and covalent binding was measured. Autoradiography of solvent-extracted tape-sections showed that all isomers were selectively and covalently bound in the lung alveolar region. As determined by exhaustive extraction of homogenized tissue, maximal binding was observed 4 hr after injection, although the lung/liver concentration ratio increased for 12 days. Covalent protein binding was also observed in vitro, implying that the activation of DDD to a reactive metabolite takes place in the target organ. Since the aryl-chlorine substitution pattern did not change the selective lung binding, bioactivation of DDD may take place at the ethane side-chain. PMID- 2587513 TI - Metabolism of 4-hydroxyanisole: identification of major urinary excretory products. AB - The human metabolism of 4-hydroxyanisole was investigated by the analysis of urine samples from melanoma patients treated with this substance. The samples were hydrolyzed with glucoronidase and/or arylsulphatase, extracted with ethyl acetate, and, after derivatization with pentafluoropropionylanhydride, analyzed by gas chromatography-mass spectrometry. We were able to identify peaks by their retention times and mass spectra corresponding to 4-hydroxyanisole, 3,4 dihydroxyanisole, and two of its o-methyl derivatives, namely, 3-hydroxy-4 methoxy- and 4-hydroxy-3-methoxyanisole. We also detected a peak of hydroquinone, which may have originated (at least partly) from 4-hydroxyanisole. All the above mentioned compounds were excreted predominantly as sulphates and glucuronides. Only a small proportion of the substances was present in urine in an unconjugated form. Our results demonstrate that 3,4-dihydroxyanisole is the most important metabolite of 4-hydroxyanisole. PMID- 2587512 TI - Effects of intravenous bumetanide administration on renal haemodynamics and proximal and distal tubular sodium reabsorption in conscious rats. AB - The renal effects of 0.02-62.5 mg/kg bumetanide given as intravenous bolus injections were studied in water diuretic conscious rats. Clearances of 14C tetraethylammonium, 3H-inulin and lithium were used as markers for renal plasma flow (RPF), glomerular filtion rate (GFR) and proximal tubular output, respectively. Bumetanide caused biphasic, transient and dose-independent changes in the renal haemodynamics without significant alterations of the filtration fraction. At dose-levels above 0.02 mg/kg bumetanide increased urine flow, absolute and fractional Na excretion as well as the indices for fractional output of Na from the proximal tubules (CLi/CIn) and the distal nephron segments (CNa/CLi). The changes in CLi/CIn became maximal at doses above 0.5 mg/kg, whereas CNa/CLi was increased with the dose up to 12.5 mg/kg. Paradoxically, doses above 12.5 mg/kg were less natriuretic due to a decrease of CNa/CLi. It is concluded that in rats bumetanide is an effective although short-acting diuretic when administered intravenously. When comparing peak responses bumetanide is equipotent to furosemide but has a lower maximal efficacy. Judged from the changes in fractional lithium excretion, the natriuretic effect of bumetanide is effected by inhibition of Na reabsorption in the proximal tubule in addition to the well-known effect on the distal nephron segment. PMID- 2587514 TI - Induction of DNA-protein crosslinks in melanotic cloudman S91 mouse melanoma cells and EMT6 mouse mammary carcinoma cells by monochromatic 254 and 405 nm light. AB - The rates of induction of DNA-protein crosslinks (DPC) by monochromatic radiation at 254 and 405 nm were compared in melanotic S91 mouse melanoma cells and EMT6 mouse mammary carcinoma cells. At 254 nm, the rates of induction of DPC are the same in the two cell lines, whereas, at 405 nm, the rate of induction of DPC in the melanotic cells is considerably less than that in the nonmelanotic cells. Since the major difference in the two cell lines with respect to absorption is melanin, the latter finding implies that intracellular melanin can protect against this DNA damage caused by a component of environmental carcinogenic solar radiation. PMID- 2587516 TI - Second meeting of the Panamerican Society For Pigment Cell Research. Bethesda, Maryland, April 23-26, 1989. Abstracts. PMID- 2587515 TI - Ultrastructural observations of motile iridophores from the freshwater goby, Odontobutis obscura. AB - The ultrastructure of "motile" iridophores of Odontobutis obscura and the changes in cell shape related to the motility were studied with electron microscopy. Various structural details were revealed by this method, and their importance is discussed. Of particular interest were the abundant microfilaments observed in the cortical cytoplasm. Cross-sectional profiles of iridophores showed that, in an iridophore in the dendritic state, the platelets were scattered randomly throughout the centrosphere and its processes, so that the centrosphere appeared to be rather flat. In the punctate state, the platelets were gathered, in groups or in stacks with regular arrangements, in the centrosphere, which appeared to be ovoid in shape. The most notable finding was that, at this time, the processes from which the platelets were lost remained there without retracting. The results indicates clearly that the motility of the goby iridophores involves the migration of platelets within the fixed contour of each cell and that no amoeboidal changes in the shapes of the cells occur. PMID- 2587517 TI - [Arteriovenous lung fistula--diagnosis and surgical therapy]. AB - Congenital pulmonary arteriovenous fistula is a rare condition and, for this reason, is repeatedly misinterpreted despite the typical complaints it gives rise to. On the basis of seven cases diagnosed and treated surgically by the present authors, including follow-up, the clinical picture is discussed in detail. The diagnosis of pulmonary arteriovenous fistula can be established on the basis of pulmonary antiography or, more simply, with the aid of digital subtraction angiography with representation of multiple fistulas and accurate localisation. Employing segmentectomy, it usually proves possible successfully to treat even multiple arteriovenous fistulas in the lung, and to achieve lasting freedom from symptoms and recurrent disease. Even if it is asymptomatic, pulmonary arteriovenous fistula should always be resected, since life-threatening ruptures with followed by bleeding into the parenchyma and haemothorax (as was observed in one of our patients) can occur. PMID- 2587518 TI - ["Pneumonia following bronchography"]. PMID- 2587519 TI - [The use of klofelin for studying somatotropin secretion in children]. AB - A stimulation clonidine test was performed in children for a study of STH secretion. The drug was injected at a dose of 0.15 m per 1 m2 of body surface. A total of 47 children were investigated. Of them 21 were healthy, with normal growth and 26 with constitutional retardation of growth (CRG). Maximum values of STH secretion were observed 60-90 min. after clonidine administration. Mean values of a STH secretion peak exceeded the initial ones greater than 8-fold in both groups without significant differences between them. Side-effects were insignificant and of transient nature. Thus clonidine is a sensitive, easy to use and safe stimulator of STH secretion. We revealed no difference in STH secretion between children with normal growth and those with CRG. PMID- 2587520 TI - [Dopaminergic regulation of the hypothalamo-hypophyseal system in patients with hypophyseal adenomas]. AB - A study was made of the state of the hypothalamohypophyseal system in patients with different types of chromophobe adenoma. Altogether 62 patients were examined using metoclopramide and Parlodel tests (38 patients were with somatotropinoma, 13--with prolactinoma, 11--with somatotropinoma with hyperprolactinemia). The time course of STH, PRL and TSH secretion in the blood was investigated. Dopaminergic blockade in the Metoclopramide test was shown to cause no change in the time course of PRL secretion in patients with prolactinomas, and a PRL reaction in patients with somatotropinomas and adenomas with PRL and STH hypersecretion was sharply decreased. A paradoxical STH reaction (a decrease) in somatotropinomas and considerable disorders in the type of PRL and TSH secretion in all forms of adenomas was defined in the Parlodel test (a dopaminergic agonist). The results obtained suggest considerable disorders in the dopaminergic regulation of the hypothalamohypophyseal system of patients with chromophobe adenomas and the efficacy of the metoclopramide and Parlodel tests in the differential diagnosis of these conditions. PMID- 2587521 TI - [The use of fat and protein metabolic indices in assessing the compensation status of diabetics]. AB - The examination of 448 patients with diabetes mellitus has shown that the use of indices of cholesterol, nonesterified fatty acids, ketone bodies, residual nitrogen, urea and creatinine using range normal limits permits the assessment in combination with clinical findings of the state of compensation. Change in the state of fat and protein metabolism was shown to be related, to a great extent, with a type of diabetes rather than with a patient's age. PMID- 2587522 TI - [The level of glycosylated hemoglobin A1c in the erythrocytes of patients with diabetic angio- and polyneuropathies]. AB - The level of glycosylated Hb A1c in erythrocytes of 173 patients with types I and II diabetes mellitus was analyzed with regard to compensation of disease, the presence and a degree of expression of diabetic angiopathies. An elevated level of Hb A1c in decompensation of diabetes decreased after achieving normoglycemia and aglycemia without reaching the normal level. The development of severe diabetic angiopathies, especially nephro- and retinopathies was accompanied by a decrease in the level of Hb A1c in decompensation up to values which could be observed during compensation of diabetes mellitus. A conclusion is that the level of Hb A1c in erythrocytes of patients with diabetes mellitus as an indicator of carbohydrate metabolic compensation can be used only in persons with unaffected vessels or at the early stages of the development of vascular affection. PMID- 2587523 TI - [The use of conjunctival biomicroscopy and liquid-crystal thermography in diabetes mellitus in children and adolescents]. AB - The importance of liquid-crystal thermography alongside with conjunctival biomicroscopy for the detection and verification of the nature of microcirculatory disorders and for the control of therapeutic efficacy was shown during the examination of 87 children and adolescents with diabetes mellitus. It has been proved that differentiated use of vasoactive drugs (Xauthnol Nicatinate, Andecalin, Pyrinolcarbamat) in patients with microcirculatory disorders exceeds 1.5-1.7-fold the results obtained in the control groups. PMID- 2587524 TI - [A new diagnostic index of diabetes mellitus based on the 2-dimensional parameter of glucose kinetics]. AB - A new approach to forming a one-part model of glucose kinetics in an i.v. tolerance test (IGTT) made it possible to introduce a two-dimensional parameter of glucose kinetics which reflected, on the one hand, the rate of glucose elimination from the blood and, on the other hand, glucose production by the liver during testing. This parameter serves the basis for a discriminant function which can be used for the identification of patients with diabetes mellitus with 100% reliability (22 patients and 50 healthy persons in a control sampling), overdiagnosis being made in 8% of the cases only. Another function characterizing a degree of carbohydrate metabolic derangement in persons with previously diagnosed diabetes is based on the same principle. Besides, a new highly reliable diagnostic criterion of diabetes mellitus was obtained taking into account a distance and position of the two-dimensional parameter of glucose kinetics with relation to a discriminant curve permitting quantitative characterization of carbohydrate metabolism in an examinee. PMID- 2587525 TI - [The implementation of a strategy for the primary prevention of diabetes mellitus]. AB - A pyruvate test for glucose tolerance was used during prophylactic medical examination of 47 students and 27 children without risk factors, 54 students with risk factors, 31 patients with type I diabetes mellitus and 220 construction workers in order to test a new methodological basis for the strategy of primary prevention of diabetes mellitus. The investigations showed the presence in a general population of 3-modal distribution of a variant of the capillary blood pyruvate level on the 120th min. of a GTT according to physiological glucose tolerance, potential (prediabetic) and actual (diabetic) carbohydrate metabolic derangements. A high informative value of the pyruvate test for glucose tolerance makes this method appropriate for identification of persons, genetically predisposed to the development of diabetes mellitus, for implementation of a population strategy of prevention of this disease as well as strategy of prevention of diabetes among persons with risk factors. PMID- 2587526 TI - [The lipid composition and aggregating capacity of thrombocytes in hyper- and hypothyroidism]. AB - The aim of the work was to investigate the phospholipid composition and parameters of platelet aggregation in patients with hypo- and hyperthyroidism. The data obtained have shown that phospholipid liposomes added exogenously, changed the function of cell hemostasis and, in particular, decreased platelet aggregation. Unlike the other phospholipids, phosphatidylinositol, cardiolipin and phosphatidylserine produced the most significant effect on this index and corrected, to a certain extent, disturbed platelet functions in hypothyroidism. PMID- 2587527 TI - [Primary hyperparathyroidism in patients with bilateral nephrolithiasis]. AB - Experience in the diagnosis and treatment of the renal form of primary hyperparathyroidism in 57 patients with bilateral nephrolithiasis was summed up. The main diagnostic criterion was the detection of biochemical changes in the blood and urine (hypercalcemia, hypophosphatemia, hypercalciuria) and the use of some tests (Howard's test and parathyroidin test). Parathyroidectomy was performed after establishing diagnosis. A new stage in therapy of such patients was a study of renal function and phosphocalcium metabolism after parathyroidectomy. The improvement of some indices (an increase in glomerular filtration, urea excretion with urine and relative urine density, and a decrease in hypercalciuria and hyperphosphaturia) indicated the effectiveness of surgical intervention for primary hyperparathyroidism in patients with bilateral nephrolithiasis. It was also confirmed by a decrease in lithogenic relapse after parathyroidectomy. PMID- 2587529 TI - [Teaching patients principles of self-control--a reserve for increasing the effectiveness of treatment of diabetes mellitus (a lecture)]. PMID- 2587528 TI - [Euthyroid hyperplasia (a summing up of the results of a discussion)]. PMID- 2587530 TI - [The soft tissues of the foot in acromegaly]. AB - X-ray investigation of foot soft tissues and measurement of foot soft tissue thickness (FSTT), clinical examination and determination of the level of plasma STH were performed in 43 previously untreated patients with acromegaly and in 9 patients in clinical remission. The results obtained suggest that elevated FSTT over 22 mm and changes in foot soft tissues are characteristic for acromegaly. A conclusion is that determination of the state of foot soft tissues and a FSTT value can serve as an auxiliary sign for the diagnosis of early stages of disease as well as for the assessment of a degree of activity and efficacy of long-term results of therapy of acromegaly. PMID- 2587532 TI - [Interrelations of circadian and minute rhythms in Wistar rats after space flight on the bio-space station "Kosmos-1129"]. PMID- 2587531 TI - [The neuronal reaction of the amygdaloid complex in the dynamics of the estrous cycle]. AB - For investigation of the structural and functional organization of the amygdaloid complex (the cerebral neuroendocrine center) a response of its neurons to the fluctuations of circulating hormones was studied in the time course of the estrous cycle. Karyometry of 22 zones of the corticomedial group and 25 zones of the basolateral groups of the structure of the amygdaloid complex was performed in adult Wistar rats. A response of neurons of several zones of the corticomedial group of nuclei was revealed. A response of neurons of the basolateral nucleus at the caudal level of the central region was revealed in the basolateral group of structures of the amygdaloid complex. PMID- 2587533 TI - [The effect of weightlessness on the minute rhythm of sensor and motor functions in monkeys]. PMID- 2587534 TI - [Oscillations of thyroid gland hormones in rats]. PMID- 2587535 TI - [Daily dynamics of indicators of carbohydrate metabolism in rat tissue after irradiation at various times of the day]. PMID- 2587536 TI - [Circadian rhythm of lipid levels in the rat bone marrow and thymus: the effect of starvation at various times of the day]. PMID- 2587538 TI - [Physiologic correlates of the flight load]. PMID- 2587537 TI - [Multiday metabolic rhythms in rats]. PMID- 2587539 TI - [Daily rhythms of human body temperature during clinostatic hypokinesis]. PMID- 2587540 TI - [Dynamics of mental productivity during a relatively free day schedule]. PMID- 2587541 TI - [Oscillating processes in the human external respiration system during passive orthostatic exposure]. PMID- 2587542 TI - [Changes in the bronchial tree under the influence of pelotherapy in patients with pulmonary tuberculosis]. AB - It was shown with using the clinical materials relating to 400 patients with pulmonary tuberculosis that peloids such as humisole, torfot and peloidin used in combination with antituberculous drugs had a favourable effect on involution of specific and nonspecific processes in the bronchi and restoration of bronchial patency. This also permitted a decrease in the terms for elimination of inflammatory lesions in the tracheobronchial tree. Phonophoresis with peloidin proved to be the most efficient procedure of pelotherapy since its use provided summation of the therapeutic effects of the mud preparation and ultrasound vibrations as well as local action on the affected organ. PMID- 2587543 TI - [The endoscopic bronchial picture of patients with pulmonary tuberculosis of various age groups]. AB - Endoscopic pictures of the bronchi were studied in 509 new cases of pulmonary tuberculosis. Tuberculosis of the bronchi and its aftereffects such as cicatricial lesions were detected in 31.1 per cent of the children and adolescents, 7.9 per cent of the adults at the age of 18 to 29 years, 9.0 per cent of the adults at the age of 30 to 55 years and 14.7 per cent of the adults at the age of 56 to 75 years. Nonspecific endobronchitis was diagnosed in 27.9 per cent of the children and adolescents, 44.9 per cent of the adults at the age of 18 to 29 years, 46.3 per cent at the age of 30 to 55 years and 44.1 per cent at the age of 56 to 75 years. The incidence and nature of tuberculosis of the bronchi and nonspecific endobronchitis were not related to the patients' age. PMID- 2587544 TI - [Natural killers in the blood of patients with limited forms of pulmonary tuberculosis]. AB - Activity of natural killer cells in blood of 47 new cases of limited tuberculosis of the lung was studied during their complex examination. There was a significant decrease in the activity of the natural killer cells in tuberculous patients which could be used as an additional criterion of the specific process activity. PMID- 2587545 TI - [The systemic immunity of schoolchildren from foci of tuberculosis infection]. AB - Seventy-eight tuberculin-positive schoolchildren at the age of 7 to 15 years from tuberculosis foci living in special institutions of the sanatorium type were subjected to immunological examination. The control group included 22 noninfected children of the same age. Persons with lower counts of T-lymphocytes and their decreased functional activity, unbalance in their subpopulation composition and positive immunospecific responses to tuberculin predominated among the schoolchildren subjected to the examination. The state of the B-lymphocyte system changed insignificantly. It was concluded that persons with markedly suppressed cellular immunity be treated with immunomodulating agents during the chemoprophylaxis course. PMID- 2587546 TI - [The status of patients with tuberculosis--migrants and those who have resided in other areas--and their treatment results]. AB - The problem of patients who returned from other territories and were previously observed in other tuberculosis institutions is analyzed. Their number is gradually increasing. With an example of some tuberculosis dispensaries of Kiev where registration of persons from other territories is limited it was shown that 88 per cent of the patients lived in Kiev: 47.5 per cent of them were intracity migrants and 52.5 per cent were persons who returned to Kiev after living for prolonged periods in other territories. The two groups of the patients markedly differed by their social and clinical status. There were more troubles with the group of the patients who arrived after living for prolonged periods in other territories since the greater proportion of such patients included discharged prisoners, heavy alcohol drinkers and patients without compliance with their therapy. Low treatment efficacy of such patients required special approaches. Respective proposals are presented. PMID- 2587547 TI - [Disorders of the ventilatory mechanics in patients with respiratory sarcoidosis]. AB - The state of the ventilation apparatus was studied in 158 patients with active sarcoidosis of the respiratory organs. The following methods were used: spirography, registration of the curve of the flow-volume of forced expiration, body plethysmography and esophageal intubation. Various disorders in the ventilation mechanics were detected. They included impairment of bronchial patency, impairment of air distribution in the lungs, changes in the elastic properties of the lung tissue, increased respiration work per 1 1 of ventilation, etc. Impairment of the small bronchi patency (in 66.5 per cent of the patients) and impairment of air distribution in the lungs were the most frequent and the most pronounced disorders in the respiration mechanics. They played a significant role in lowering of the lung ventilation capacity and increasing of energy supply for respiration. PMID- 2587548 TI - [The nonspecific microflora of patients with newly detected active pulmonary tuberculosis complicated by bronchial obstruction]. AB - Eighty-five new cases of active pulmonary tuberculosis and bronchial obstruction in some of them were subjected to bacteriological and serological examinations (quantitative estimation of nonspecific microflora and indirect immunofluorescence test, respectively). Combination of the methods made it possible to show that bronchial obstruction in 52.8 per cent of the cases was due to the presence of nonspecific microflora and that Str. pneumoniae played the leading role in its development in 32.1 per cent of the cases. PMID- 2587550 TI - [Tuberculosis morbidity in regions with a low population density]. AB - Tuberculosis incidence was studied in the northern areas of Irkutsk Province with low population density. In the areas slower lowering of pulmonary tuberculosis incidence was noted. The main contingent of the new cases included persons with the disease detected during fluorographic examinations. In the areas with low population density, the percentage of the new cases with tubercle bacilli isolation and late diagnosis of tuberculosis was higher than in the areas with high population density. The influence of migration on the epidemiological status with respect to tuberculosis in the areas with low population density was less significant as compared to that in the areas with high population density. PMID- 2587549 TI - [Lung changes in rats under the action of paraquat and the importance of antioxidants]. AB - Characteristic features of pulmonary lesions after exposure to paraquat and various antioxidants were studied in albino rats. The antioxidants included dibunol, sodium thiosulfate and its combination with alpha-tocoferol. In the treated animals, there was a marked decrease in the areas affected by atelectasis and lower severity of elastofibrosis, involution of the connective tissue evident from its thinner fascicles and destruction of the collagenous and elastic fibers. PMID- 2587551 TI - [The effect of hormonal therapy on the functioning of phagocytosing blood cells in patients with sarcoidosis]. AB - It was shown that the functional state of neutrophils and monocytes in the peripheral blood of patients with sarcoidosis lowered which was evident from their lower absorbing capacity, lower numbers of the EAC-rosette-forming cells and higher metabolic activity. Prior prednisolone therapy influenced the functional state of neutrophils: the cell ability to reduce NBT and the activity of acid phosphatase decreased while the lysozyme levels and absorption capacity increased. The functional state of monocytes was in general the same in the patients treated and untreated with the glucocorticoid. PMID- 2587552 TI - [The diagnosis of silicotuberculosis activity]. PMID- 2587553 TI - [The diagnostic value of prescalene biopsy]. PMID- 2587555 TI - [Suppurative brain inflammation in patient with pulmonary tuberculosis]. PMID- 2587554 TI - [The tuberculin-pharmaco-indigo carmine provocation test in the diagnosis of renal tuberculosis and the determination of its activity]. PMID- 2587556 TI - [The use of a fluorographic chamber with x-ray diagnostic apparatus for conducting prophylactic examinations of the population]. PMID- 2587557 TI - [Combined tuberculosis and cancer of the lungs]. PMID- 2587558 TI - [Enhanced work efficiency in agricultural workers with surgically treated pulmonary tuberculosis]. AB - Recommendations were developed and proposed for rational employment of agricultural workers operated on for pulmonary tuberculosis. The proposals were formulated with regard to the volume of the work done, impairment of the respiration and cardiovascular systems, activity of the specific lesions in the remaining lung tissue, character of the previous job and differential periods: short-term periods up to 1 year, medium-term periods up to 2 years and continuous periods of over 2 years. PMID- 2587559 TI - [Bronchogenic cancer in patients in the diagnostic department of a tuberculosis hospital]. PMID- 2587560 TI - [A giant benign tumor of the lung]. PMID- 2587562 TI - [Recurrence of pulmonary tuberculosis in a patient with histiocytosis X]. PMID- 2587561 TI - [Hepatitis during rifampicin and isoniazid treatment of a patient with generalized tuberculosis]. PMID- 2587563 TI - [Hemoptysis in a patient with a leech in the larynx]. PMID- 2587564 TI - Destinations in pathology. PMID- 2587565 TI - Evaluation of cyclosporine nephrotoxicity by renal transplant fine needle aspiration. AB - Fine needle aspiration is a relatively safe, minimally invasive technique for morphologic evaluation of intragraft events in renal transplant recipients. We assessed the usefulness of this technique in the diagnosis of acute cyclosporine nephrotoxicity (NT). Two aspirate features considered indicative of NT were examined; tubular cell cytoplasmic isometric vacuolization (IV) and isolated graft lymphocytosis. Fifty-six adequate aspirates from 22 patients receiving cyclosporine were evaluated by the method of Hayry and von Willebrand. Retrospectively, four groups were identified for the purpose of this study: A, greater than 50% tubular cell population with IV (N = 11); B, less than 50% tubular cell population with IV (N = 15); C, graft lymphocytosis without IV (N = 15); D, normal aspirates (N = 15). A retrospective clinical diagnosis of cyclosporine NT was present at the time of ten aspirations in Group A (91%) and one each in Groups B (7%) and C (7%, P less than 0.001). No patients with aspirates in Group D had NT. The remaining aspirates were from patients with multiple clinical diagnoses. Plasma cyclosporine levels did not correlate with IV or graft lymphocytosis. Serum creatinine levels were higher in patients from Group A as compared with Group D (P less than 0.03). We conclude that not all patients treated with cyclosporine or diagnosed with clinical cyclosporine NT demonstrate IV or lymphocytosis in graft aspirates. However, when isometric vacuolization occurs in greater than 50% of tubular cells, acute cyclosporine NT must be considered strongly. Isolated graft lymphocytosis is a nonspecific finding. PMID- 2587566 TI - Lymphoproliferative disorders and hematologic malignancies following organ transplantation. AB - Eleven allograft recipients (one cardiac, one hepatic, nine renal) at the Massachusetts General Hospital developed a lymphoproliferative disorder or leukemia. Six (all renal) patients received conventional immunosuppressive therapy (CIT), four received cyclosporin A (CsA) (one cardiac, one hepatic, two renal), and one received CIT for his first transplant and CsA for his second transplant (both renal). The interval from transplant to onset of the hematologic disorder ranged from 2 mo to 3 yr in the CsA group and from 6 mo to 9 yr in the CIT group and was 16 yr in the patient with two allografts. There were eight malignant lymphomas, seven of which were extranodal, (four immunoblastic, one large noncleaved cell, one small noncleaved cell, one plasmacytoma, one unclassifiable), one case of polymorphic diffuse B cell hyperplasia and two cases of acute myeloid leukemia. Frozen section immunohistochemistry in six cases showed monotypic immunoglobulin in four lymphomas, (including the plasmacytoma), an immunoglobulin-negative B cell phenotype in one lymphoma, and polytypic immunoglobulin in the case of polymorphic hyperplasia. One lymphoma showed a monotypic immunoglobulin-producing B cell population in one site and an immunoglobulin-negative B cell population in another site. With an immunoglobulin heavy chain gene-specific probe, Southern blot analysis of tissue from these two sites revealed two distinct rearrangements. When tissue from a second case of lymphoma was analyzed by Southern blot, identical rearrangements of the heavy chain gene were found in tumor from two separate sites. Similar to the experience of others, we find an increased incidence of lymphoma and a slightly increased incidence of acute myeloid leukemia in allograft recipients. In contrast to other reports, we found a predominance of monoclonal B cell malignancies, a more polymorphous histologic appearance of the lymphoproliferative disorders in CsA patients, and one case each of "multiclonal" and "monoclonal" lymphomas when tumor from separate sites was tested for gene rearrangement. PMID- 2587567 TI - Cutaneous myofibroma. AB - The clinical and pathologic features of an acquired skin tumor, which histologically is identical to infantile myofibromatosis, are presented. Thirty four cases were studied, 26 of which were in patients over 14 yr of age. The median age was 36. None of the lesions was associated with recurrence after surgery, and metastases were not observed. Microscopically, the lesions were relatively well circumscribed and had a characteristic biphasic pattern which centrally showed features of vascular tumors, including hemangiopericytoma or glomus tumor. Ultrastructural examination identified cells with features of myofibroblasts, glomus cells, and pericytes. Immunoreactivity for muscle actin was strongly and diffusely positive in all tumors. The clinical significance of this entity lies primarily in its recognition as a distinctive benign neoplasm, most probably of vascular origin. The occurrence of this lesion is not limited to children; it may be an acquired lesion, and it may be found in the skin as well as soft tissue. PMID- 2587568 TI - Carcinoembryonic antigen in medullary thyroid carcinoma: an immunohistochemical study applying six novel monoclonal antibodies. AB - Six novel mouse monoclonal antibodies raised against carcinoembryonic antigen (CEA) were used to study 22 medullary, ten papillary, ten follicular, and eight anaplastic thyroid carcinomas. The antibodies CEA 12-140-5, -7, and -10 reacted with the same epitope group (GOLD 4), whereas antibodies CEA 12-140-1, -2, and -4 recognized different epitopes (GOLD 5, 2 and 1, respectively) on the CEA molecule. All medullary carcinomas of the thyroid (MCTs) were stained when the antibodies CEA 12-140-5, -7, and -10 were applied, whereas CEA 12-140-1 stained all but five MCTs; CEA 12-140-2 and CEA-12-140 -4 each stained all but two. The CEA immunoreactivity was predominantly located diffusely in the cytoplasm but occasionally was also concentrated along the cell membrane. CEA immunoreactivity was also observed in normal C-cells and C-cell nodules. The follicular, papillary, and anaplastic carcinomas were all CEA-negative with the monoclonal antibodies applied in this study. The differences in staining pattern of MCTs found with the various antibodies may be explained as a lack of expression of some epitopes in some tumors, or they may be due to a varying degree of masking of the epitopes by the extensive glycosylation of CEA and CEA-like substances. PMID- 2587569 TI - Immunohistochemical evaluation of neoplasms in bone marrow biopsies using monoclonal antibodies reactive in paraffin-embedded tissue. AB - A panel of commercially available monoclonal antibodies (MoAbs) including LN1, LN2, MB2, L26, Leu M1, UCHL1, MT1 and L60 was used to evaluate a diverse group of neoplastic processes in 256 Zenker's-fixed, decalcified, paraffin-embedded bone marrow biopsies using the ABC immunoperoxidase technique. LN2 and MB2 were useful in delineating the extent of B-cell lymphoproliferative processes and in identifying interstitial patterns of involvement. The combined application of LN2, MB2 and UCHL1 had utility in differentiating B-cell from T-cell lymphoproliferative processes; in no instance was reactivity with LN2 observed in T-cell processes. The combined application of these three MoAbs was also used in differentiating benign reactive lymphoid aggregates from focal malignant B-cell proliferations. LN2 exhibited positivity with the Reed-Sternberg cells (RSC) of Hodgkin's Disease (HD) and significantly aided in the identification of these cells. Staining of RSC with Leu M1 was inconsistent and was observed in only 50% of cases of HD. Use of the entire panel of MoAbs together with more recently available reagents such as Cathepsin G, MAC 387 and neutrophil elastase was essential in optimally evaluating a particular lesion; none of these MoAbs used singly reliably differentiated myeloid from lymphoid, hematopoietic from metastatic, or reactive from malignant processes. PMID- 2587570 TI - The intrathyroidal hyperfunctioning parathyroid gland. AB - Six cases of primary hyperparathyroidism due to hyperfunctioning intrathyroidal parathyroid glands are reported. In five cases, hyperparathyroidism was due to an intrathyroidal parathyroid adenoma; in the sixth case, hyperparathyroidism resulted from an intrathyroidal parathyroid carcinoma. All five patients with adenoma were female with ages ranging from 40 to 70 yr. The patient with carcinoma was a 55-yr-old male. In all five patients with intrathyroidal parathyroid adenoma, thyroidectomy was performed when an abnormal parathyroid gland could not be located in the neck during surgery for hyperparathyroidism. The patient with intrathyroidal parathyroid carcinoma presented with hypercalcemia and a palpable right thyroid mass. The differential diagnosis of intrathyroidal parathyroid adenoma includes thyroid follicular adenoma. In some cases, the possibility of medullary carcinoma of thyroid might also be considered. Immunocytochemical staining for parathormone (PTH), thyroglobulin, and calcitonin is valuable in establishing the correct diagnosis. PMID- 2587571 TI - Nucleolar organizer regions in superficial spreading melanoma with nodule. AB - Nucleolar organizer regions (NORs) are genes coding for the ribosomal RNA; they also induce the formation of the nucleolus at interphase. Transcriptionally active NORs can be visualized in histological sections with a silver colloid method, allowing direct counting of these structures (so-called AgNORs). Seven superficial spreading melanomas with nodule (i.e., melanomas containing both a radial and a vertical growth phase) were studied with the technique. The nuclear AgNOR counts (mean +/- SEM) were 5.44 +/- 1.70 for the radial growth phase and 7.65 +/- 2.35 for the vertical growth phase (P less than 0.01). This difference in mean nuclear AgNOR numbers may be related to other known differences in the biological behavior of the two growth phases. PMID- 2587572 TI - Localized amyloidosis of seminal vesicles: report of three cases in surgically obtained material. AB - Localized amyloidosis of the seminal vesicles (ASV) is reported as an incidental finding in surgical specimens from three elderly men. In two cases, the amyloid deposits were bilateral, subepithelial, and clinically inapparent, features similar to other cases in the literature. In one case, the diagnosis was made on a transrectal prostatic needle biopsy that included a small portion of seminal vesicle; to our knowledge, this has not been previously reported. Electron microscopy in one case demonstrated nonbranching fibrils characteristic of amyloid, and pretreatment of tissue sections using the permanganate method in two cases showed almost complete ablation of congophilia. Evidence suggests that ASV is a permanganate-sensitive, non-AA (amyloid, protein A) type of amyloid that may be different from all other types of amyloid previously characterized. PMID- 2587573 TI - Sertoli-Leydig cell tumor associated with a mature cystic teratoma in a single ovary. AB - Sertoli-Leydig cell tumors of the ovary are rare neoplasms of young women and are best known for their frequent virilizing effects. They have very rarely been reported in association with other ovarian neoplasms. We report such a tumor associated with a mature cystic teratoma in the same ovary. The wide variety of histologic patterns seen in many Sertoli-Leydig cell tumors including the present case, often causing difficulty in diagnosis, is reviewed. PMID- 2587574 TI - Skin hygiene. PMID- 2587575 TI - A patient's view of ileostomy. AB - What is it like to have a stoma? There are many implications--physical and psychological, good and bad. This is one woman's account of her illness, operation and life post-ileostomy. PMID- 2587576 TI - A question of cooperation: managing community mental handicap nurses. AB - Setting up an inter-agency community mental handicap service in the Rhondda involved creating new management structures to enable nurses to do their jobs effectively. PMID- 2587578 TI - Managing pressure sores: local treatment. PMID- 2587577 TI - Will I be in pain? Patients' and nurses' attitudes to pain after abdominal surgery. AB - This small-scale study found that nurses did not always administer all the analgesia prescribed to patients, even though patients reported suffering pain. PMID- 2587579 TI - Patient information: the key to increased automony. AB - When a gynaecology nurse practice group realised women were often given conflicting information about their treatment, they decided to produce a comprehensive range of information sheets. An example of one of their sheets is included with this article. PMID- 2587580 TI - What shall I do when I get home? Advice for women who have had a hysterectomy or vaginal repair. PMID- 2587581 TI - Are you fully insured? AB - It is an unfortunate aspect of modern life that insurance is vital in a number of areas. Our financial services series continues with a look at the different types of insurance and advice on how to get the best deals. PMID- 2587582 TI - Don't lose that job! Effective applications. PMID- 2587583 TI - Implementing Project 2000--time to speak out! AB - Unless we understand what is proposed by Project 2000 and speak up for the fundamental values of nursing, the reforms will not bring about the improvements in the quality of patient care we seek. This article is the first in a new series on Project 2000. PMID- 2587584 TI - Exercise-induced anaphylaxis: epidemiologic observations. PMID- 2587585 TI - Phylogeny of the plasma regulatory proteins of the complement system. PMID- 2587586 TI - Binding of human C3a and the synthetic nonapeptide C3a (tyr-70-77) to rat peritoneal mast cells. PMID- 2587587 TI - Interaction of immunoglobulin A with complement and phagocytic cells. PMID- 2587588 TI - Human renal kallikrein-kinin system after engraftment and/or immunosuppression. PMID- 2587589 TI - Modulation of the allergic response by fish oil lipids and eicosatrienoic acid. PMID- 2587590 TI - Behavioral effects of diltiazem injected into the paraventricular nucleus of the hypothalamus. AB - The calcium channel inhibitor diltiazem is widely used as a medication for cardiovascular diseases. Some side effects have been reported after its administration, including changes in activity (apathy or hyperactivity) and feeding behavior (anorexia). Previous experiments have found that local administration of various peptides into the paraventricular nucleus of the hypothalamus can have profound effects on these two behaviors. In the present study, effects of local infusions of diltiazem into the paraventricular nucleus on locomotor activity and food intake have been tested. A marked hyperactivity, greater than the hyperactivity caused by intraperitoneal injection of amphetamine was produced. Feeding behavior was not affected one hour after the infusions but intraventricular diltiazem infusions decreased feeding behavior. It is concluded that the paraventricular nucleus of the hypothalamus has an important role in the regulation of locomotor activity and that diltiazem can act at this level to produce behavioral changes. PMID- 2587591 TI - The effects of type-1 and type-2 diabetes on endothelium-dependent relaxation in rat aorta. AB - Diabetes mellitus is known to produce alterations in vascular reactivity. In the present study we have examined the effects of endothelium-dependent and endothelium-independent relaxing substances on thoracic aorta from insulin dependent (Type-1) and noninsulin-dependent (Type-2) diabetic rats and their appropriate controls. Endothelium-dependent relaxations produced by acetylcholine and histamine in aortic rings precontracted with noradrenaline were significantly increased in insulin-dependent diabetic vessels. In contrast, the relaxations elicited by those agents were significantly attenuated in noninsulin-dependent diabetic aorta preparations. On the other hand, the relaxations induced by sodium nitroprusside (an endothelium-independent relaxant agent) in both types of diabetic preparations were comparable to those in control vessels. The results indicate that insulin-dependent and noninsulin-dependent diabetes lead to specific alterations of the endothelium-dependent relaxation of rat aorta. PMID- 2587592 TI - Some morphometric evidence of hepatoprotective effects of (+)-cyanidanol-3. AB - The (+)-cyanidanol-3 is used as an antihepatotoxic and hepatoprotective drug in both men and animals against alcoholic and experimental liver injury. Histologic staining techniques give mostly qualitative or semiquantitative description of liver damages. Experiments have been carried out to determine the hepatoprotective effects of (+)-cyanidanol-3 on alcoholic liver damage (i.e., fatty liver and hepatomegaly) by morphometric measurement of the liver tissue sections. Ethanol was administered ad lib to CFY rats to cause mild alcoholic liver damage together with 200 mg/kg/day (+)-cyanidanol-3 to prevent the tissue deterioration. The changes of hepatic lobule and hepatocytes were measured morphometrically. The chronic ethanol consumption results in hepatocellular hypertrophy, a significant increase in size of the hepatocytes and a mild increase of the intralobular extrahepatocytic space as well when compared with controls. The volume of cytoplasm was increased while the parameters of nuclei were unchanged. The (+)-cyanidanol-3 prevents changes and the morphometric parameters in the treated group were almost the same as in the controls. The treatment with (+)-cyanidanol-3 alone does not affect the hepatic tissue parameters. The results show the hepatoprotective effect of (+)-cyanidanol-3 and the suitability of the morphometric method for quantitative comparison of normal and experimentally-altered liver cells. PMID- 2587594 TI - Opiate effects on social behavior of juvenile dogs as a function of social deprivation. AB - The relationship between opioids and social behavior was examined by administering morphine (an opioid agonist) and naloxone (an opioid antagonist) to juvenile dogs and measuring various social behaviors (e.g., tail wagging) in a large room. Drugs were administered following social deprivation and nondeprivation. It was hypothesized that morphine would ease effects of social deprivation while naloxone would result in behavior typical of untreated socially deprived dogs. Social deprivation (24 hr) resulted in more contact with the experimenter and increased tail wagging relative to nondeprivation. Morphine (0.25 mg/kg) resulted in more contacts with the experimenter and entrances into the "experimenter's area" relative to vehicle injections. Further, morphine decreased and naloxone increased tail wagging in the dog's area and there was a significant social condition X drug interaction for that measure. Naloxone (0.25 mg/kg) increased wagging following nondeprivation while morphine decreased wagging following deprivation. These data support the hypotheses that social deprivation can increase social behaviors, and that social behavior is regulated by activity in brain opioid systems. PMID- 2587593 TI - Discriminative stimulus properties of local anesthetics in d-amphetamine- and pentobarbital-trained pigeons. AB - Pigeons were trained to discriminate either d-amphetamine (1.7 mg/kg, IM) or pentobarbital (10 mg/kg, IM) from saline in a two-key, food-reinforced drug discrimination paradigm. Cocaine, procaine, and lidocaine were administered before test sessions to determine if these local anesthetics shared discriminative stimulus (DS) properties with either training drug. Cocaine (0.1 3.0 mg/kg) substituted for d-amphetamine in all 4 birds from the d-amphetamine trained group. Procaine (3.0-56 mg/kg) substituted in 3 of the 4 birds from this group, and lidocaine (3.0-30 mg/kg) did not substitute in any bird. In contrast, cocaine, procaine, and lidocaine did not substitute for pentobarbital in any bird in the pentobarbital-trained group. These results suggest that the DS properties of some local anesthetics may be similar to those of psychomotor stimulants. Further, although some local anesthetics may have sedative-like actions, apparently these are not the basis of their DS effects. PMID- 2587595 TI - Effect of chronic neonatal morphine and naloxone on sensorimotor and social development of young rats. AB - Chronic morphine treatment of newborn Long-Evans rat pups between 3-26 days of age (thrice daily starting with 0.5 mg/kg, increased daily by 0.5 mg/kg to 10 mg/kg) led to lags of 1 to 3 days in physical development (body weights and eye opening times) and motor coordination (catalepsy test, grasping, swimming). Chronic naloxone treatment (5 mg/kg administered thrice daily from day 3-26), in contrast, led to modest gains in development on a number of measures (body weights, vaginal opening). Morphine animals also lagged behind controls and naloxone-tested animals in social behaviors, such as homing and play. Chronic naloxone did not block or retard social development; in fact naloxone-treated animals exhibited more rapid acquisition of homing behavior than controls. PMID- 2587596 TI - Characteristics of radiation-induced performance changes in bar-press avoidance with and without a preshock warning cue. AB - Rats were trained to perform one of three tasks in which responses on a lever delayed the onset of footshock for 20 sec. One task provided a warning tone beginning 15 sec after the last response on the lever and lasting for 5 sec just prior to the presentation of a shock (fixed-interval signalled avoidance), while a second task provided no external cues (unsignalled avoidance). The third task was similar to the fixed-interval signalled avoidance task, except that the warning tone preceding shock began at varying intervals after the last response on the lever (variable-interval signalled avoidance). Animals trained on the signalled avoidance paradigms received fewer shocks than those on the unsignalled avoidance paradigm. After 10 krads of gamma radiation, animals performing on either task with cues were less able to avoid shock, although they recovered somewhat over a 90-min period. The animals not provided cues also experienced more shocks during the first 10 min after irradiation but were relatively less affected in performing the task. Response rates on the bar and the patterns of responding on these tasks were not significantly different after irradiation, except that animals responded after the onset of shock more often after irradiation than before. These results suggest that rats will continue to effectively use task related cues after irradiation, but that the relative degree of behavioral decrement may depend on the initial level of performance or possibly the complexity of the task. PMID- 2587597 TI - Neonatal administration of oxytocin increases novelty-induced grooming in the adult rat. AB - Three-day-old Sprague-Dawley rat pups were intracisternally infused with a single dose of oxytocin (1 microgram/2 microliters) or saline, or were untreated. As adults, these animals were observed for novelty-induced grooming, analgesia measured by the hot-plate test, and behavior in the open field. Oxytocin treatment during infancy resulted in an elevation of novelty-induced grooming when compared to saline and untreated animals. There were no significant oxytocin treatment effects on analgesia response or open-field behaviors. Oxytocin given early in life may have permanent effects on certain behavioral responses to stress. PMID- 2587598 TI - Evidence for a behavioral deficit during withdrawal from chronic nicotine treatment. AB - Rats that had been trained to respond for food on a fixed-interval 3-minute schedule were treated once daily with nicotine (2 mg/kg) for 50 days. Animals developed marked tolerance to the depressant effect of nicotine as measured by the decreased effect of the treatment dose on response rates over days. Substitution of saline for nicotine during chronic treatment resulted in response rates which were significantly less than pretreatment values. In addition, following cessation of chronic treatment, response rates were initially suppressed below pretreatment rates; by the third day of withdrawal, response rates had returned to baseline levels. It is proposed that the response deficit observed during nicotine absence represents one behavioral component of a nicotine withdrawal syndrome. PMID- 2587599 TI - The effects of amphetamine and chlorpromazine on independent ingestion of milk in preweanling rats. AB - To assess the effects of catecholaminergic drugs on independent feeding during development, preweanling rats were administered amphetamine (AMPH) or chlorpromazine (CPZ) and were allowed to ingest milk through anteriorly located intra-oral cannulas. In 1-hr milk-deprived rat pups, AMPH stimulated milk intake at 3, 7 and 10 days of age and suppressed intake at 15 days. In 22-hr-deprived pups, AMPH had no effect at 3, 7 and 10 days, but reliably suppressed intake at 15 days. CPZ stimulated intake in 3-, 10- and 15-day-old milk-satiated pups. In 22-hr-deprived pups, CPZ had no effect at 3 and 10 days, but stimulated intake at 15 days. While AMPH produced pronounced nonappetitive behavioral activation in conjunction with enhanced intake in 1-hr-deprived pups, AMPH-induced activation occurred without enhanced intake in 22-hr-derived pups. Thus, there was a dissociation between AMPH's effect on milk intake and AMPH-induced nonappetitive behavioral activation. Collectively, the present results support the following conclusions. First, a catecholaminergic system(s) that enhances independent feeding is present very early in postnatal development of the rat. Second, level of food deprivation is an important state-dependent variable when assessing the effects of AMPH and CPZ on independent feeding in preweanling rats. PMID- 2587600 TI - Signal detection analysis of ethanol effects on a complex conditional discrimination. AB - The effects of ethanol on a conditional object identification task were investigated using an operant analog of Signal Detection Analysis. Water and three doses of ethanol (0.40, 0.75 and 1.5 g/kg) were orally administered on three separate occasions to three adult squirrel monkeys. Significant discrimination impairment as a function of increasing ethanol dose was observed. At the 1.5 g/kg dose, impairment extended to nonspecific effects, with subjects ceasing to respond early into the session. Subsequent signal detection analyses revealed that the reduction in performance resulted from losses in discriminability. Response bias was found to change unpredictably and independently of ethanol administration. Reaction time measures also showed no changes except a moderate, nonsignificant, facilitation in speed at the lowest (0.40 g/kg) dose. Taken together, these data suggest that ethanol acts to impair complex, or cognitive, performance by disrupting current sources of stimulus control within the range of doses tested. PMID- 2587601 TI - Pantethine, a somatostatin depleting agent, increases food intake in rats. AB - During the course of studies of the effects of pantethine, a cysteamine precursor known to deplete tissue concentration of immunoreactive somatostatin, we observed that the subject rats continued to eat despite marked distension of the stomach. To determine whether this effect was caused by drug-altered food intake, we have measured food and water intake in pantethine-injected rats in the fed and fasting state. In three separate experiments, rats allowed free access to food until the morning of study showed significant increased food intake accompanied by an increased stomach content (at 4 hr) of both food and water following the IP injection of pantethine. In one experiment, intake at 3 hours was 0.60 g/100 g b.wt. (pantethine dose 0.74 g/kg b.wt.) and 0.64 g/100 g b.wt. (pantethine dose 1.47 g/kg b.wt.) compared with 0.24 g/100 g b.wt. in saline-treated animals (p less than 0.05). In contrast, pantethine, 1.47 g/kg b.wt., when administered to overnight-fasted rats, significantly inhibited food intake (3-hr intake 1.54 +/- 0.16 g/100 g b.wt. in rats injected with pantethine 1.47 g/kg b.wt. as compared with 3.3 +/- 0.21 g/100 g b.wt. in saline-injected controls). The intake stimulating effect of pantethine in ad lib-fed rats was not demonstrable when the drug was administered shortly before the "lights out"-induced feeding at night. These findings indicate that pantethine, a cysteamine precursor, stimulates food intake in satiated rats, depending upon the stage of circadian rhythm, but is inhibitory to intake in fasted animals. We postulate that the effects are mediated directly or indirectly through the disinhibition of central appetite regulating somatostatinergic pathways but, since cysteamine also inhibits dopamine-beta-hydroxylase, an effect on depletion of appetite-regulating central catecholamines cannot be excluded. PMID- 2587602 TI - Weight loss and altered circulating GI peptide levels of rats exposed chronically to nicotine. AB - This study was undertaken in male Sprague-Dawley rats to test the hypothesis that chronic ingestion of a low dose of nicotine suppresses body weight gain. The results from this study suggest that chronic nicotine ingestion induces weight loss in rats without the loss of their food intake. To determine whether the nicotine-induced body weight reductions are associated with endocrinological changes, the levels of gastrin and CCK in plasma were measured by specific radioimmunoassays and were found significantly elevated during chronic ingestion of nicotine. The data indicate that reduction of body weight mass by nicotine might be dependent on both hormonal and metabolic factors. PMID- 2587603 TI - Serotonin binding sites during proestrus and following estradiol treatment. AB - The binding of 3H-5-HT to hypothalamic, hippocampal and striatal membranes from female rats was examined. During the day of proestrus, there was a significant increase in binding from morning to evening. The increase reflected changes in both Kc and Bmax. Effects of estradiol were examined in ovariectomized rats, and changes in 3H-5-HT binding resulted from an increase in the Kd after estradiol treatment. These in vivo effects of estradiol were not seen when tissue was incubated in vitro with estradiol. However, the compound, polyvinylpyrrolidone, used in the in vitro incubation significantly increased the Kd for binding to 3H 5-HT and estradiol attenuated the increase. The potential significance of these changes to serotonin's modulation of reproductive function is discussed. PMID- 2587604 TI - Food and nicotine metabolism. AB - To examine the plausibility of the hypothesis that smoking a cigarette after a meal is motivated by accelerated metabolism of nicotine, we studied the influence of a high-protein meal on the disposition of nicotine in seven healthy smokers. Indocyanine green clearance, an estimate of hepatic blood flow, increased 31%, 50 minutes after the test meal. Consuming the meal during a steady state infusion of nicotine resulted in a small (18%) but consistent decrease in blood levels of nicotine. Our data demonstrate that food accelerates the metabolism of nicotine, but the time course and magnitude of the decline in levels of nicotine suggest that altered disposition of nicotine is not the primary motivation for smoking after meals. PMID- 2587605 TI - Alprazolam but not diazepam protects hamsters with heart disease from the medical consequences of stress. AB - We have previously shown that subjecting cardiomyopathic hamsters in the lesion developing period of their heart disease to cold-immobilization stress had lethal consequences which could be blocked by alprazolam treatment. This experiment replicated that finding and also examined the efficacy of diazepam in this paradigm. In contrast to alprazolam, diazepam did not prevent the cardiomyopathic subjects from succumbing to the stressor. Thus, the effect of alprazolam in reducing stress-induced mortality did not reflect a generic benzodiazepine action. PMID- 2587606 TI - L364,718 antagonizes the cholecystokinin-induced suppression of locomotor activity. AB - To determine the role of CCK-A receptors in the cholecystokinin (CCK)-induced suppression of locomotor activity in the rat, the ability of the selective CCK-A receptor antagonist L364,718 to block these responses was investigated. Cholecystokinin octapeptide (CCK8) (10, 100 micrograms/kg IP) and caerulein (1, 5, 10 micrograms/kg IP) produced marked reductions in locomotor activity whereas cholecystokinin tetrapeptide (CCK4) (100 micrograms/kg IP) was without effect. The reductions in activity produced by CCK8 (10 micrograms/kg) and caerulein (10 micrograms/kg) were antagonized by L364,718 (100 micrograms/kg IP). In an open field test CCK8 (10 micrograms/kg IP) reduced locomotor activity and total number of rears and increased pause duration. These effects of CCK8 on open-field behaviour were also antagonized by L364,718 (100 micrograms/kg IP). It is concluded that L364,718 is a potent antagonist of the actions of CCK8 and caerulein on locomotor activity, suggesting that the effects of these peptides are mediated by a CCK-A receptor. PMID- 2587607 TI - A pretest procedure reliably predicts performance in two animal models of inescapable stress. AB - Rats exposed to inescapable tailshock fail to learn a shuttle-escape task 24 hours later, an effect referred to as "learned helplessness." However, within most rat strains only 10-50% of the animals tested develop this syndrome. In the present study a significant correlation was found between rats that displayed learned helplessness on the first test and those that displayed learned helplessness on a second test performed either 2 weeks (r = .80, p less than 0.001) or 4 weeks (r = .74, p less than 0.001) later. An analysis of the mean session latency of the shuttlebox task in these two tests suggested a bimodal distribution of animals that failed and learned. A significant correlation was found between individual rats that learned this task on the first test and those which learned this task 2 or 4 weeks later. Similarly, in the "behavioral despair" test, a significant correlation was observed for floating time for individual rats on the first test and on the second test either 2 (r = .72, p less than 0.001) or 4 weeks (r = .63, p less than 0.001) later. However, for the forced-swim test, a unimodal and rather graded response was observed across individual subjects. Thus, performance on the first round predicted performance on the second round in both models. When rats experienced the learned helplessness paradigm on round 1 and the behavioral despair paradigm in round 2, there was no correlation between rats that displayed helplessness following inescapable tailshock and the rats that demonstrated "behavioral despair" on a later test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2587608 TI - Genetic influences on nicotine responses. AB - Male mice from 19 inbred strains were tested for the effects of nicotine on six responses: respiratory rate, acoustic startle response, Y-maze crosses, Y-maze rears, heart rate and body temperature. Dose-response curves were constructed for each strain on each test in a multitest battery. Results indicated that the responses were strongly influenced by the genotype of the animal. Comparison of the results from the six tests measured in this study and the results previously reported for nicotine-induced seizures in these same strains indicated that the responses could be grouped into two major classes: a set characterized by Y-maze crosses, Y-maze rears and body temperature and a set characterized by seizure sensitivity and seizure latency. Responses observed for respiratory rate and startle response shared characteristics with both of these sets, while nicotine effect on heart rate was fairly unique. The results have identified strains of mice which are differentially sensitive to the effects of nicotine. PMID- 2587609 TI - Variation of nicotinic binding sites among inbred strains. AB - The specific binding of L-nicotine and alpha-bungarotoxin, two ligands which label different populations of putative nicotinic receptors, was determined in eight brain regions of 19 inbred mouse strains. The dissociation constants for L nicotine (average = 2.26 nM) and alpha-bungarotoxin (average = 0.31 nM) did not vary significantly among the brain regions or strains. In contrast, significant variability among the maximal binding sites was observed between regions and among the strains within a region. Significant differences in L-nicotine binding were observed among the strains in midbrain, hindbrain, hippocampus, hypothalamus and colliculi, while little variability was noted in cortex or cerebellum. In general, those strains that had high L-nicotine binding in one region had high nicotine binding in the other regions. The strains clustered into two large groups: one group expressing relatively low binding and a second group expressing relatively high binding. Significant differences in alpha-bungarotoxin binding were observed in seven of the eight regions measured and, in general, those strains with high binding in one region tended to have high binding in the other regions. The strains clustered into three groups: those with low binding (DBA/1 and DBA/2), those with high binding (ST/b alone) and those with intermediate binding (the remaining 16 strains). The amount of binding of the two ligands did not correlate with each other. Comparison of nicotinic ligand binding with physiological response to nicotine suggests a relationship of L-nicotine binding with several responses observed after injection of low doses of nicotine and a relationship between alpha-bungarotoxin binding and nicotine-induced seizures. PMID- 2587610 TI - Effects of stereoselective 5-HT1A agonists on male rat sexual behavior. AB - The effects on male rat sexual behavior of some new stereoselective 5-HT agonists, related to 8-OH-DPAT, are presented. It was found that (+)cis-8-hydroxy 1-methyl-2-(di-n-propylamino) tetralin (8-OH-MeDPAT), as well as (-)trans-2-(2 hydroxyphenyl)-N,N-di-n-propylcyclopropylamine (2-OH-DCPA), and its 3-hydroxy phenyl analog (3-OH-DCPA), stereoselectively facilitated the male rat sexual behavior, as evidenced by a decrease in the number of intromissions preceding ejaculation, and a shortening of the ejaculation latency. For the former two compounds, studied in further detail, the potency and efficacy appear to be of the same magnitude as previously found for 8-OH-DPAT. The results demonstrate specific 5-HT receptor involvement in the mediation of male rat sexual behavior. PMID- 2587611 TI - Suppression of juvenile social behavior requires antagonism of central opioid systems. AB - Pairs of male and female rats were injected with either tertiary naltrexone (NTX) which readily crosses the blood-brain barrier, or quaternary naltrexone (QNTX) which does not, to determine the importance of central opioid systems in the elaboration of juvenile social behavior. In the first experiment, only intraperitoneal injections of NTX (1.0 mg/kg) suppressed the frequency of wrestling pins. Peripheral injections of QNTX (10.0 mg/kg) were without effect. In a second experiment, QNTX (2.0, 4.0, or 8.0 micrograms/4.0 microliters) was injected directly into the lateral ventricles. Intracerebroventricular injection of the moderate dose reliably reduced frequency of pinning while the higher dose was severely incapacitating and the low dose was without effect. The results of these two experiments confirm an important role for brain opioid systems in the control of juvenile social interaction. PMID- 2587612 TI - Pregnenolone sulfate antagonizes barbiturate-induced hypnosis. AB - The potential influence of the neurosteroid pregnenolone sulfate (PrS) on barbiturate-induced hypnosis was tested in rats. PrS, when injected intracerebroventricularly or intraperitoneally, significantly shortened the sleep time produced by pentobarbital. The results suggest an important physiological and pharmacological role for PrS in the regulation of CNS excitability. PMID- 2587613 TI - Effects of repeated testing on the incidence of haloperidol-induced catalepsy in mice. AB - Effects of repeated testing on the incidence of haloperidol-induced catalepsy were investigated in mice. The incidence of catalepsy, evaluated with the forelimbs or hindlimbs placed on a standard horizontal bar, increased in three successive tests in mice injected with haloperidol. Catalepsy was not provoked by repeated testing in animals with saline. In a subsequent study, mice were examined for catalepsy in the forelimbs in the first two trials and then in the hindlimbs. In this procedure, the incidence of catalepsy did not increase with repeated testing. These results suggest that repeated testing increases the incidence of haloperidol-induced catalepsy but does not influence the cataleptogenic potency of the drug. PMID- 2587614 TI - Pharmacological manipulations of sucrose consumption in the Syrian hamster. AB - Nondeprived, male Syrian hamsters (Mesocricetus auratus) were adapted to a daily schedule of 2-hr access to a 10% sucrose solution. Two benzodiazepines, midazolam (1.0-10 mg/kg) and flurazepam (1.0-10 mg/kg), produced dose-dependent increases in sucrose consumption. In contrast, the alpha 2-adrenergic agonist, clonidine (0.01-0.3 mg/kg), had no effect on sucrose intake. Neither d-fenfluramine nor d amphetamine affected sucrose ingestion in the hamsters, except at a large dose (10 mg/kg). Nevertheless, significant, dose-dependent reductions in sucrose consumption were observed after the administration of either opiate antagonists (naltrexone; nalmefene) or selective dopamine D2 receptor agonists (N-0437; quinpirole). The results are compared and contrasted with previously reported data for rats. PMID- 2587615 TI - Chronic imipramine does not block cocaine-induced increases in brain stimulation reward. AB - Self-stimulating rats implanted with ventral tegmental area electrodes were tested with 15 mg/kg cocaine HCl before and after chronic imipramine treatment. Chronic imipramine had no influence on cocaine's ability to lower brain stimulation reward thresholds, suggesting that tricyclic antidepressant treatment does not block cocaine-induced euphoria. PMID- 2587616 TI - Methylphenidate plasma concentrations in chronically and acutely treated latency age children. AB - In 5 latency-age boys, methylphenidate plasma concentrations following multiple doses of methylphenidate were consistently higher than those obtained after a single dose. Pharmacological and clinical implications are discussed. PMID- 2587617 TI - Pharmacokinetics of galanthamine hydrobromide after single subcutaneous and oral dosage in humans. AB - Galanthamine hydrobromide (Nivalin, dose 10 mg) was given subcutaneously and orally to 8 volunteers. Galanthamine and its metabolites were quantified in plasma and urine by reversed-phase HPLC. An unusual two-stage absorption and biexponential drug decline were observed. Galanthamine plasma peaks (1.24 micrograms/ml after subcutaneous and 1.15 micrograms/ml after oral doses) were reached 2 h following administration, the t1/2(beta) values being 5.70 and 5.26 h, respectively. Minor epigalanthamine and galanthaminone plasma levels were detected. An almost complete urinary recovery of galanthamine and its metabolites was obtained within 72 h. The plasma AUC, Cmax, tmax and ka suggest that the subcutaneous and oral Nivalin formulations are bioequivalent. PMID- 2587618 TI - Dietary myo-inositol effect on sugar cataractogenesis. AB - The lens myo-inositol (MI) content is known to be depleted during initial cataractogenesis in both streptozocin (STZ)-induced diabetic and 50% galactose maintained rats. The objective of this study is to establish whether dietary MI supplementation protects lens transparency, MI content and individual fiber cell ultrastructure is both model systems of sugar cataract. In the diabetic study, after induction with STZ, rats were immediately placed on normal chow supplemented with 2% MI for 14 weeks while additional age-matched control and diabetic rats remained untreated. Within 14 weeks, untreated diabetic rat lenses were totally opaque with undetectable MI content; MI was undetectable by 1 month. These opaque lenses were devoid of fiber cells and exhibited only acellular, amorphous cortical regions between 0 and 500 microns from the capsule. In contrast, 14-week, MI-treated diabetic rat lenses exhibited only cortical vacuolation indicative of initial cataractogenesis; MI content was 0.41 +/- 0.26 mumol/g wet weight of lens. Scanning electron micrographs indicated a granulated, acellular region subadjacent to the capsule and confirmed the presence of cortical fiber cells, approximately 100 microns from the capsule. In 50% galactose-maintained rats, daily administration of MI for 1 month was unable to prevent total opacification or reverse initial cataractogenesis indicating that in rapidly progressing galactose cataracts, MI was unable to protect lens transparency, MI content and cortical fiber ultrastructure. The combined results suggest that MI may exert a protective effect on the slowly developing diabetic cataract. Of the 2 models, the time course and polyol content in STZ diabetic lenses more closely correlate to the human diabetic lens which has a low activity of aldose reductase; therefore, it is possible that MI may exert a protective effect in human diabetic cataract. PMID- 2587619 TI - Human liver cytochrome P-450 related to a rat acetone-inducible, nitrosamine metabolizing cytochrome P-450: identification and isolation. AB - A monoclonal antibody (MAb) to a rat acetone-inducible and nitrosamine metabolizing form of microsomal cytochrome P-450, P-450ac, detected a related P 450 in human liver microsomes by both immunoblot and competitive radioimmunoassay. This MAb was also used to immunopurify microsomal cytochromes P 450 from both human liver and acetone-treated rats; these were electrophoretically homogeneous with apparent molecular weights of 56,200 and 53,000 daltons, respectively. The structures of the cytochromes P-450 were compared by peptide mapping and amino-terminal sequence analyses. They differed in their peptide maps but displayed amino-terminal sequence similarity in their first 19 residues. This report thus demonstrates the utility of MAbs to rat cytochromes P-450 for detection, identification and structural characterization of human P-450s. PMID- 2587620 TI - Effect of repeated administration of U-50,488H, a kappa opioid receptor agonist, on central 5-HT1 and 5-HT2 receptors in the rat. AB - The effect of repeated administration of U-50,488H, a kappa-opioid receptor agonist, on the development of tolerance to its analgesic effect and on the 5-HT1 and 5-HT2 receptors in the cerebral cortex and spinal cord of the rat were determined. Male Sprague-Dawley rats were injected twice daily with U-50,488H, (25 mg/kg, i.p.) or its vehicle for 4 days. The assessment of tolerance to the analgesic effect and biochemical determinations were made on day 5. Repeated administration of U-50,488H resulted in the development of tolerance to its analgesic effect. The 5-HT1 and 5-HT2 receptors were characterized by using 3H-5 hydroxytryptamine (3H-5-HT) and 3H-spiperone as the ligands and unlabeled 5 hydroxytryptamine (5-HT) and ketanserin, respectively, to determine the nonspecific binding. In the spinal cord 3H-5-HT bound to 5-HT1 receptors at a single high-affinity site with a Bmax value of 41.3 +/- 9.6 fmol/mg protein and a Kd value of 22.6 +/- 7.0 nmol/l. 3H-Spiperone bound to 5-HT2 receptors in the spinal cord with a Bmax value of 16.1 +/- 3.8 fmol/mg protein and a Kd value of 0.36 +/- 0.15 nmol/l. Repeated administration of U-50,488H to rats did not affect spinal cord 5-HT1 and 5-HT2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2587621 TI - In vitro and in vivo action of diisopropylfluorophosphate, of atropine and their synergism on acetylcholinesterase activity. AB - Modifications of acetylcholinesterase (AChE) activity, caused by diisopropylfluorophosphate (DFP) and atropine and their synergism, were determined in vitro and in vivo in the rat. In vitro atropine caused a reduction of the AChE activity, but reduced the enzyme inhibition by DFP. These results are discussed in the light of the evidence that AChE is an allosteric enzyme. In vivo the AChE inhibition by DFP is in part reduced by atropine. The limited protection of AChE by atropine may be one of the factors implied in the reduction of the DFP toxicity by atropine. PMID- 2587623 TI - Effect of noradrenaline on rubidium (86Rb) efflux in the rat isolated seminal vesicle. AB - The effect of noradrenaline (NA) on the efflux of rubidium (86Rb) from the rat isolated seminal vesicle was studied in the absence and presence of phentolamine and papaverine. Strips of spirally cut seminal vesicles were incubated in radioactive 86Rb (10 microCi.ml-1) for 2 h. Radioactivity was measured using an autogamma spectrometer, and the flux data were expressed in terms of rate constants per minute, of the reactive isotope efflux. A concentration-effect curve for the effect of NA on rat seminal vesicles was constructed, alone and in the presence of phentolamine (1 mumol/l) or papaverine (5 mumol/l). The results showed that NA (10-1,000 mumol/l) produced concentration-dependent contractions in the rat seminal vesicle. These responses were greatly reduced by phentolamine but markedly enhanced by papaverine. NA significantly increased 86Rb efflux from rat seminal vesicles (control rate constant 0.0042 +/- 0.001; test 0.0064 +/- 0.002, means +/- SE; n = 8 rats; p less than 0.001). This increase (52%) occurred within an exposure of 7 +/- 1 min to NA. Phentolamine decreased the NA-induced increase in 86Rb efflux, by 75 +/- 2%, whereas papaverine enhanced it by 86 +/- 5% of the control value. The mechanism of NA-induced increase in 86Rb efflux was not further investigated but was interpreted in terms of an increase in intracellular K+ (here represented by 86Rb), which will leave the cell (efflux) after initial membrane depolarization. PMID- 2587622 TI - Urinary excretion of ciclosporin and 17 of its metabolites in renal allograft recipients. AB - Renal elimination of the immunosuppressant ciclosporin is virtually unknown. Therefore, in 17 renal allograft recipients under steady-state conditions we studied the urinary excretion of ciclosporin and 17 of its metabolites in blood and 24-hour urine. Patients with liver dysfunction or treated with drugs potentially influencing the metabolism and elimination of ciclosporin were excluded from the study. Ciclosporin and its metabolites were measured by HPLC. Metabolite but not ciclosporin excretion was strongly correlated with creatinine clearance. Metabolites 18 and 26 (beta, epsilon-cyclic metabolite) were rarely found in blood but were excreted in considerable amounts in urine. Approximately 3% of the administered dose of ciclosporin per day undergoes renal elimination in unchanged form or as metabolites investigated. The data suggest glomerular filtration of ciclosporin metabolites, a difference in the rate of elimination between ciclosporin and the metabolites and some kind of metabolism or active transport mechanism for metabolites in the kidney. PMID- 2587624 TI - Pharmacological comparison of the isolated whole urethra model to urethral strip methodology. AB - Urethral strips provide a sensitive method for quantitative pharmacology; however, it is not clear if the physiological response of the whole urethra to pharmacological agents can be extrapolated from these data. The intent of this study was to investigate whether the linear contraction of strips is consistent with the ability of the intact urethra to alter resistance to flow. To measure the effect of drugs on the ability of the intact urethra to alter resistance to flow in the absence of endogenous influences, we developed an in vitro whole rabbit urethra model. We characterized the effect of norepinephrine in the absence and presence of alpha-adrenergic antagonists (prazosin, yohimbine, and LY253352) on intraurethral pressure which was measured during constant saline infusion using a Statham pressure transducer. We compared this to the contractile function of urethral strips. The pA2 values for alpha-adrenergic antagonists, LY253352, prazosin, and yohimbine were 8.17 +/- 1.5, 6.49 +/- 1.2, and 5.58 +/- 0.9, respectively, as determined in the whole urethra. The pA2 values for these antagonists determined in urethral strips were as follows: LY253352 8.72 +/- 1.2; prazosin 7.52 +/- 1.5, and yohimbine 5.6 +/- 0.84. Pharmacologically, the whole urethra model and isolated strips appeared to respond similarly to alpha adrenergic agonists and antagonists, and thus both models would be suitable for pharmacological studies on the normal urethra. PMID- 2587626 TI - Studies of the cavitational effects of clinical ultrasound by sonoluminescence: 4. The effect of therapeutic ultrasound on cells in monolayer culture in a standing wave field. AB - In previous work the phenomenon of sonoluminescence (SL) has been used to find the conditions in which transient cavitation during exposure to ultrasound is likely to be maximum. This paper reports the effect of therapeutic ultrasound on growth of mouse tumour cells in monolayer culture when the cells are insonated either at a pressure antinode or at a pressure node in a standing wave ultrasound field that is known to produce strong bands of SL at the pressure antinodes. Reduced cell numbers 72 h after insonation were recorded when the cells were insonated at an antinode but not when they were at a node. The possibility that this effect might be an artefact of the experimental system, and further experiments that could elucidate the nature of the damage, are discussed. PMID- 2587625 TI - Effects of famotidine at the mouse neuromuscular junction compared with those of cimetidine and ranitidine. AB - The effects of some histamine H2-receptor antagonists on the cholinergic system have been evaluated at the mouse end-plate. Previous data revealed interactions at both pre- and postsynaptic sites for cimetidine and ranitidine. The present work shows the effects of the same two drugs, and of famotidine, on some parameters related to the neuromuscular transmission. Ranitidine potentiates the amplitude of the spontaneously occurring miniature end-plate potentials. Famotidine reduces the same parameter. A common effect achieved with higher concentrations of the three drugs is the reduction of the quantal content. The kinetic parameters of the quantal conductance change is lengthened, in a different manner, by all the assayed drugs too. These results, besides strengthening the hypothesis of an inhibitory action of ranitidine on acetylcholinesterase, indicate a collateral inhibitory effect at presynaptic levels of cimetidine, ranitidine and famotidine. PMID- 2587627 TI - The role of non-acoustic factors in the induction and proliferation of cavitational activity in vitro. AB - It is well known that a liquid exposed to relatively low intensities of MHz ultrasound may or may not cavitate depending upon a variety of non-acoustic factors. This paper shows that in some cases the material used as the acoustically transparent window and even the length of the sample chamber may also be important factors. Cling film, dialysis membrane and Parafilm are all equally acceptable as acoustically transparent windows for ultrasound, whereas glass cover slips or 'soft' surfaces (in which active bubbles may embed themselves) are not. All the results obtained confirm the validity of bubble recycling as being the dominant mechanism responsible for the enhancement of cavitational activity commonly observed when the sample chamber is rotated. PMID- 2587628 TI - Use of a fibre-optic hydrophone in measuring acoustic parameters of high power hyperthermia transducers. AB - A fibre-optic hydrophone consisting of a polarisation-maintaining fibre carrying light from a laser source has been used to measure the acoustic output parameters of a single focused hyperthermia transducer and a six-transducer assembly. Beam profiles of the transducers were measured using the fibre-optic hydrophone and the results compared with those obtained using a PVDF hydrophone. The acoustic power output from the hyperthermia transducer was measured using a radiation force balance. It was observed that the root mean square voltage of the fibre optic hydrophone output is proportional to the square root of the acoustic power up to more than 80 W. It was also observed that, under continuous-wave operation, the fibre optic hydrophone can stand up to very high power (more than 200 W) without being damaged. As its sensing element is the fibre itself, whose diameter is considerably narrower than the width of the ultrasonic beam, it can provide resolution of about 80 microm in beam profile measurement. The fibre is a line sensor and a computer tomographic technique is used to recover the pressure profile from the hydrophone output voltage. In typical clinical operations, the six-transducer assembly is driven with less than 150 W of electrical power input. In such cases, each individual transducer receives less than 25 W of input power and non-linearity and generation of high frequency harmonics at the focus is not a significant problem. PMID- 2587629 TI - Reflections on tissue characterisation. AB - Theoretical predictions that absorption and velocity dispersion, in addition to characteristic acoustic impedance mismatch, mediate the reflectivity of a planar interface are explored. A technique to measure the frequency dependence of the reflectivity is described: a special hydrophone, purpose-built to this end, is utilised in order to show that perspex/water and neoprene/water reflectivities are not inconsistent with the general predictions of the theory. An approach towards displaying, simultaneously, both the temporal and spectral properties of ultrasound pulses is described, and its potential utility in both reflectivity measurement and investigation of non-linear propagation is proposed. PMID- 2587630 TI - Applicators for generating ultrasound-induced hyperthermia in neoplastic tumours and for use in ultrasound physiotherapy. AB - Ultrasound in the low megahertz frequency range is used by physiotherapists to treat a variety of conditions. The treatments reduce swelling, reduce pain and increase movement at joints. Ultrasound is now also beginning to be used to treat malignant tumours. The tumours are heated to temperatures between 42 degrees and 45 degrees C, producing cellular damage, the extent of which is determined by the duration and number of treatments and 'concurrent' treatments by chemo and x-ray therapy. In the light of the results of computer simulation, we discuss in this paper: (a) The properties of a five-element divergent transducer array to treat large superficial neoplastic tumours. The field distribution measured by the Sarvazyan method will be described and also compared with that of computer simulation. The benefits of frequency wobbling will also be discussed. (b) The possibility of employing a multiple field applicator for use by physiotherapists to obviate the need for continuous movement of a small transducer of area approximately 5 cm2 over the affected area. PMID- 2587631 TI - An experimental shock wave generator for lithotripsy studies. AB - An electrohydraulic shock wave generator has been constructed to facilitate investigation of the acoustic field generated during extracorporeal shock wave lithotripsy (ESWL). Pressure waveforms at the generator aperture and the beam focus, measured using a PVDF needle hydrophone, are compared with those from a commercial lithotripter, the Dornier HM3. PMID- 2587633 TI - Effect of hand splints on stereotypic hand behavior of girls with Rett syndrome: a replication study. AB - The purposes of this study were to replicate a recent report of the positive effects of hand splinting on the stereotypic hand movement of children with Rett syndrome and to evaluate the generality of these results to a different setting. Two 5-year-old girls diagnosed with early Stage-III Rett syndrome were introduced to hand splints in accordance with the multiple-baseline design used in the Naganuma and Billingsley study. Splint wear ranged from 30 to 50 days for the two subjects. Data were analyzed as a percentage of time and as actual time in minutes. Unlike the previous study, in which a decrease in hand-wringing behavior was noted, neither subject in our study demonstrated a decrease in stereotypic hand behavior or a subsequent increase in independent feeding skills when wearing the splints. There was also no evidence of increased hand wringing following withdrawal of the splints. The differences in ages of the subjects and different functional levels (stages) may have been contributing factors to the conflicting results and should be considered in managing this group of children. PMID- 2587632 TI - Clinical application of controlled stress to the healing extensor tendon: a review of 112 cases. AB - The purposes of this article are to describe an early passive motion program for the healing extensor tendon and to report the results and trends noted in a review of 112 complex extensor tendon injuries treated with this therapeutic technique. The rationale for this technique is based on a review of the physiologic response of healing tendon to controlled stress. Clinical application is dependent on a biomechanical study of extensor tendon excursion, which allows the therapist to apply controlled stress to the healing tendon with precision. The early passive motion technique is considered in terms of physiology, biomechanics, clinical application, and results. The author concludes that early controlled passive motion for the complex extensor tendon injury in zones V, VI, VII, T IV, and TV is a safe and effective rehabilitation technique that reduces complications associated with extensor tendon injury and repair. PMID- 2587634 TI - Basic principles of splinting the hand. AB - This article presents the basic principles needed in the fabrication of static and dynamic splints. The principles are defined, and examples are used as illustrations. The biomechanics of dynamic splinting are described, with special attention given to low-profile dynamic splinting. Several low-profile dynamic splints are described, with current indications presented in case studies with supporting documentation for appropriate splinting protocols. PMID- 2587635 TI - Placebo effect in TENS study? PMID- 2587636 TI - Oriental blepharoplasty: anatomic considerations. PMID- 2587637 TI - Regarding the harvesting of skin grafts of the proper thickness. PMID- 2587638 TI - Consolatory fantasies. PMID- 2587639 TI - Superomedial pedicle technique of reduction mammaplasty. PMID- 2587640 TI - Immediate postmastectomy reconstruction: choices and concerns. PMID- 2587641 TI - Blepharospasm and botulinum toxin. PMID- 2587642 TI - The "sponge deformity" after tangential excision and grafting of burns. PMID- 2587643 TI - Rhinoplasty imaging with the Macintosh computer. PMID- 2587644 TI - Ear salvage by the temporoparietal fascial island flap. PMID- 2587645 TI - Effect of corticosteroids in ischemia: ischemic injury. PMID- 2587646 TI - Nasal bone graft miniscrew fixation. PMID- 2587647 TI - Tessier no. 9. PMID- 2587648 TI - Free flaps for defects of the scalp and calvarium. PMID- 2587649 TI - The immediate breast reconstruction. PMID- 2587650 TI - Tensor fasciae latae VY retroposition flap. PMID- 2587651 TI - The inferior gluteal free flap in breast reconstruction. AB - The inferior gluteal musculocutaneous free flap usually provides a sufficient amount of autogenous tissue for breast reconstruction when adequate tissue is not present in the lower abdomen or back. Its arteriovenous pedicle is longer than the superior gluteal musculocutaneous free-flap pedicle and permits microvascular anastomosis in the axilla, avoiding medial rib and cartilage resection. In the thin patient, there is more available donor tissue than with the superior gluteal musculocutaneous free flap. Cadaver dissections confirm the greater pedicle length and the local area of the lower gluteus maximus muscle needed to carry the skin island and have helped define a safe approach to flap elevation. We have used four flaps for breast reconstruction without vascular compromise or the need for reexploration. The low donor-site scar in the inferior buttock fold has been acceptable, especially for a bilateral reconstruction. The anatomy of the gluteal region, the surgical technique for the inferior gluteal free-flap transfer, and a 3-year patient follow-up are presented. PMID- 2587652 TI - Measurement of capsular contracture: the conventional breast implant and the Pittsburgh implant. AB - At present, there is no accurate, reliable method of experimentally measuring capsular contracture. This study had four goals: (1) to define the parameters of capsular contracture employing principles of biomechanics of soft tissues, (2) to develop laboratory techniques to measure the parameters, (3) to design an implant that mechanically impedes the process of encapsulation, and, (4) to test this implant against a conventional one. We have developed a breast implant (the Pittsburgh implant) with an altered surface topography. Its silicone shell is punctuated by projections 1 mm in height and 1 mm in diameter. Two techniques were devised to measure contracture. The first involved measuring the force deformation along a coronal axis. The second involved measuring hydrostatic pressures within the implant resulting from the injection of known quantities of saline. Measurements were performed in vivo on 36 animals. By both force and pressure measurements, the Pittsburgh implant showed less capsular contracture (p = 0.12 and 0.012, respectively). Histology revealed that the prototype surface alters the linear arrangement of myofibroblasts and redirects the laminar collagen into a waveform pattern. We conclude from this experimental study that an altered surface topography may serve as a means of rendering a capsule less mechanically effective. We feel that the proposed methods can be used in the laboratory to characterize the extent of capsular contracture. PMID- 2587653 TI - The diagnosis of ruptured breast implants. AB - This study is a retrospective review of 18 patients treated by the authors and 14 reported patients with ruptured breast implants. A history of trauma was absent in 11 patients; 17 patients had closed capsulotomies. The physical findings of ruptured implants were nodules, decreased breast size, asymmetry, tenderness, and a softer texture. Mammograms were 90 percent accurate when silicone had migrated. In seven of eight false-negative mammograms, silicone was contained within the fibrous capsule. Mammography signs of rupture are summarized. The diagnosis of ruptured implants should be facilitated by recognition of the clinical presentations and radiographic signs. PMID- 2587654 TI - Microtia reconstruction: does the cartilage framework grow? AB - The use of free rib cartilage ear frameworks in unilateral microtia reconstruction has prompted much discussion about their potential for growth. The senior author has reconstructed ear frameworks in 132 microtia patients, most of whom were under 3 years of age when surgery was initiated. Of this group, 29 were assessed for ear growth through comparison of the lead-plate model of the original normal ear to the normal ear growth and the reconstructed ear framework after a period of at least 2 years. Similarly, 14 reconstructed ears were compared to 14 normal ears at least 2 years after reconstruction. The perimeters of tracings made from the original lead plates and of tracings of normal and reconstructed ears were determined by image analysis techniques. The results demonstrated no significant difference in growth between normal ears and reconstructed ear frameworks after an interval of at least 2.5 years. Therefore, the reconstructed ear is growing at a rate similar to that of the normal ear. PMID- 2587655 TI - V-Y advancement flaps for closure of nasal defects. AB - The nose is a difficult anatomic region in which to close defects resulting from resection of cutaneous malignancies. The V-Y flap is a technique for advancing adjacent tissue, thereby achieving wound closure while minimizing tension. A total of 120 V-Y flaps were used to close 114 nasal defects. The average defect size was 13.5 x 11 mm. Partial flap loss occurred in five patients, with total flap loss in one. One wound infection and two hematomas occurred. PMID- 2587656 TI - Fat-grafting injection for soft-tissue augmentation. AB - Autogenous graft tissue is better than homologous and heterologous tissue for the improvement of body contour to eliminate deep defects in the skin surface. This paper presents techniques for fat-graft injection obtained from liposuction and the instruments specially designed for this procedure. An analytical study is presented, and the final results obtained with this method are compared with different filling materials used for aesthetic and reconstructive purposes. A statistical study of 253 operated patients in a long-term follow-up (1984-1988) is registered. Special comments have been included relative to patient recovery, the amount of fat absorption and the amount of fat tissue remaining, and fat injection revisions and complications. PMID- 2587657 TI - The integrated approach to suppurative mediastinitis: rewiring the sternum over transposed omentum. AB - Acute mediastinitis after cardiopulmonary procedures remains a devastating complication and a challenge to the reconstructive surgeon. A review of the literature and our own experience confirm the need for early aggressive drainage followed by timely reconstruction. In carefully selected patients, the sternum may be reclosed, provided that omental tissue has been transposed into the defect between the myocardium and the posterior cortex of the sternum. The technique is outlined and the results are analyzed and compared with three additional patient subgroups: (1) sternal wounds rewired over drains, (2) sternal wounds rewired with drains and irrigation catheters, and (3) wounds closed by sternal excision and muscle-flap transposition. To date, nine omental transfers have been performed with complete success. Mediastinal drainage routinely ceases after 3 to 5 days, and hospitalization has averaged 10 to 14 days. Early open debridement allows establishment of drainage and permits close evaluation of the character of the bony sternum. Muscle flaps may then be used in those patients with multiply fractured or frankly necrotic sternal tissue, while sternal closure over omental flaps may be used in all other patients. Adherence to this protocol has allowed for bacteriologic control of the wound, minimal morbidity, and no mortality. PMID- 2587658 TI - Autogenous vein graft repair of digital nerve defects in the finger: a retrospective clinical study. AB - Twenty-two digital nerve repairs were performed in the finger using autogenous vein grafts. Eighty-two percent of the repairs were available for follow-up. Results of sensibility return were assessed using moving two-point discrimination, Semmes-Weinstein monofilaments, and vibratory testing. Two-point discrimination averaged 4.6 mm for 11 acute digital nerve repairs using vein conduits 1 to 3 cm in length. Delayed digital nerve repair with vein conduits yielded poor results. Semmes-Weinstein values demonstrated comparable levels of return of slowly adapting fiber/receptors to the quickly adapting fiber/receptors, as evidenced by moving two-point discrimination tests. Vibratory sensibility was present in all. A review of previous experiences with end-to-end digital neurorrhaphies and digital nerve grafting suggests that repair of 1- to 3 cm gaps in digital nerves with segments of autologous vein grafts appears to give comparable results to nerve grafting. Further laboratory and clinical research is necessary to better define the role of interpositional vein conduits for repair of peripheral nerves. PMID- 2587660 TI - Improved healing of microvascular PTFE prostheses by induction of a clot layer: an experimental study in rats. AB - This study was undertaken to test the hypothesis that the induction of a clot layer on the graft surface of microvascular polytetrafluoroethylene (PTFE) prostheses might improve their healing. PTFE microvascular prostheses (n = 18), mechanically roughened PTFE microvascular prostheses (n = 18), and Chitosan impregnated PTFE microvascular prostheses (n = 18) (all prostheses: length 1 cm, inside diameter 1.5 mm, fibril length 30 microns) were implanted into the abdominal aortas of rats and were evaluated at 3 days (n = 3), 10 days (n = 3), 3 weeks (n = 6), and 6 weeks (n = 6) with regard to the presence or absence of a clot layer and with regard to the amount of graft healing. All untreated PTFE prostheses were never found to be covered with a clot layer, only scarcely with some platelets, and showed poor neoendothelial healing; even at 6 weeks after implantation, there was only endothelial cell coverage near the anastomotic sides (coverage = 19 +/- 4 percent). The endothelial cells were present directly on the graft surface. In contrast, both the roughened and the Chitosan-impregnated PTFE prostheses were completely covered with a thin clot layer upon implantation and demonstrated significantly better neoendothelial healing (endothelial cell coverage at 6 weeks = 76 +/- 22 percent and 75 +/- 18 percent, respectively; p less than 0.001); moreover, in these prostheses, the endothelial cells were present on a matrix of smooth-muscle cells, which covered the graft surface completely. These results confirm our hypothesis that the induction of a clot layer on the graft surface of microvascular PTFE prostheses improves their healing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2587661 TI - "There is properly no history, only biography". PMID- 2587659 TI - The tetrachlorodecaoxygen complex reverses the effect of cortisone on wound healing. AB - Immunosuppression induced by the administration of glucocorticoids will prevent normal wound contraction and normal increases in tensile strength. Vitamin A, anabolic steroids, and growth hormone will, in the presence of glucocorticoids, restore mesenchymal cell proliferation, the accumulation of collagen, and the rate of increase of wound tensile strength. They will not, however, antagonize the inhibition of wound contraction. A novel inorganic agent, the tetrachlorodecaoxygen anion complex (TCDO), known to enhance the migration and activation of macrophages, was tested in a rat model of impaired wound healing using high doses of glucocorticoids. Histology, changes in wound contraction, collagen synthesis, and tensile strength were evaluated. Animals receiving cortisone in combination with TCDO displayed markedly enhanced wound healing, including restoration of tensile strength, collagen synthesis, and wound contraction. The results indicate that TCDO could be a potential agent of wound healing in immunosuppressed patients and anergic wounds. PMID- 2587662 TI - Microcystic adnexal carcinoma (sclerosing sweat duct carcinoma). AB - Microcystic adnexal carcinoma (MAC) is a recently described malignant neoplasm of the adnexal structures of skin that shows a marked propensity for early infiltrative and locally aggressive growth. Its banal clinical appearance may lead to a delay in diagnosing the tumor by biopsy, and its multifaceted histologic features may lead to an incorrect tissue diagnosis. Confusion with benign tumors and less aggressive malignancies can lead to inadequate initial treatment and extensive recurrences. We describe three cases of microcystic adnexal carcinoma and review the clinical and histologic features, treatment, and prognosis of this neoplasm. PMID- 2587663 TI - Reconstruction of the entire esophagus with "chain flaps" in a patient with severe corrosive injury. AB - A method of reconstructing the entire esophagus by a chain of free forearm flaps connecting pharynx to jejunum is presented. This was indicated because all other means of reconstruction were not possible. It solved a difficult problem with good result, and the patient was satisfied. PMID- 2587664 TI - Webbing of the neck: correction by tissue expansion. AB - The surgical technique to correct the webbing deformity of the neck by Z-plasty corrects the deformity but leaves disfiguring scars over the lateral aspect of the neck, and the hair-bearing skin is transposed anteriorly. Butterfly correction and the lateral cervical advancement flap again correct the deformity and the low hairline but leave disfiguring scars over the posterior aspect of the neck. Recurrence is possible as a result of increased tension on the skin posteriorly. In the method described in this paper, the insufficient skin of the lateral aspect of the neck is expanded by tissue expanders. The excess skin is then advanced posteriorly, and redundant skin is excised following removal of the expanders. This corrects the webbing deformity and the low hairline, leaving a small vertical scar in the midline and a horizontal scar at the occipital area within the hairline. PMID- 2587665 TI - Prerequisite training. PMID- 2587666 TI - [The course of restitution of learning and concentrating ability in chronic alcoholics in the 1st year of abstinence]. AB - Aim of our investigation was the analysis of the performances of chronic alcoholics under abstinence. 3 groups of 30 alcoholics were investigated after 3 weeks, 3 months and one year and compared with a group of control (n = 30). The most essential results: Strong increase in the first 3 month, after only slow increase. The level of healthy population has been attained nearly but not complete. The restitution is independent of the age and sex but significant dependent to the type of drinking (gamma- and deltadrinker). This results are important for the occupational rehabilitation of alcoholics after therapy. PMID- 2587667 TI - [Episodic manifestation of hemiparkinson syndrome with severe dementia personality change and precursors of paranoid hallucination symptoms]. AB - A case of episodic manifestation of semiparalysis agitans is described, accompanied by severe demential personality change and precursory hallucinatory symptoms, which is made the basis for the discussion of aspects of mental disorders, notably dementia and symptoms resembling schizophrenia, in Parkinsonian patients. By way of allusion to Glass, a diagnosis including a very extensive, complex, symptomatology is made of a Parkinsonian syndrome. PMID- 2587668 TI - [Acute meningitis with cerebrospinal fluid eosinophilia: neurocysticercosis]. AB - Neurocysticercosis is a very rare disease in Central Europe. This is a report about an 18 year old patient with acute meningitis and eosinophilia in cerebrospinal fluid. The findings and outcome of a short treatment with Praziquantel are discussed. PMID- 2587669 TI - [Cutting of clothing while bicycling--artistic performance of a communication disordered deaf patient suffering from fetishism]. PMID- 2587670 TI - [Regression of autonomic symptoms in alcoholic polyneuropathy]. PMID- 2587671 TI - Measurement of boar sperm motility by the trans-membrane migration method. AB - The conventional microscopic methods for evaluating sperm motility of domestic animals are mostly inadequate due to their subjectivity and lack of precision. Recently, a trans-membrane migration method, originally developed for the examination of human sperm motility, has substantially overcome these problems. This study investigated the applicability of the method to boar sperm motility measurement. The apparatus used was simple and consisted only of syringe plungers, poriferous membranes, and modified multi-well culture plates. It measured the proportion of sperm in the semen that moved across the membrane after incubation at 37 degrees C for 3 hr. The sperm motility as measured by this method correlated well with that measured by direct microscopic examinations. The measurement was more reliable using an 8-microns instead of a 5-microns pore-size membrane. The method was found to work equally well for the sperm motility measurement of the semen with a sperm concentration between 1.5 x 10(8)/ml and 6.0 x 10(8)/ml. The results indicate that this method is a simple, objective, quantitative, and reproducible design for the measurement of boar sperm motility. PMID- 2587672 TI - [New selective monoamine oxidase inhibitors in the treatment of depressive disorders]. PMID- 2587673 TI - [Comparison of the new MAO-A inhibitors moclobemide, brofaromine and toloxatone with tranylcypromine in an animal experiment: significance for clinical practice]. AB - The rat studies presented in this manuscript show that the new non-hydrazine compounds moclobemide, brofaromine and toloxatone have a profile typical of monoamine oxidase-A (MAO-A) inhibitors. These inhibitors are short-acting (16-24 h), reversible, non-hepatotoxic and have only low liability to potentiate tyramine pressor effects (cheese-effect). The present results in rats and the clinical trials provide evidence that moclobemide is an orally active MAO-A inhibitor which, due to its remarkably low tyramine potentiating pressor effects and to its lack of anticholinergic activity, has a very attractive pharmacological profile. In contrast to moclobemide, tranylcypromine is an irreversible and mixed MAO-A and MAO-B inhibitor with long-lasting effects. This hydrazine derivative is not devoid of hepatotoxic effects and markedly potentiates tyramine pressor effects. Moclobemide, being a particularly safe MAO A inhibitor, seems to be an effective new compound for the therapy of exogenous and endogenous depressive states. PMID- 2587675 TI - [Psychometric findings in treatment using the selective MAO-A inhibitors moclobemide and maprotiline]. AB - Two groups of depressed patients were treated either with a selective MAO-A inhibitor, moclobemide (n = 13), or a tetracyclic antidepressant, maprotiline (n = 18), in a 28 days lasting investigation. Before and after treatment psychopathologic symptoms were rated using Hamilton Depression Scale, motor performance were proven by the Motorische Leistungs-Serie (MLS), and acoustic and visual sensorimotor performance were investigated using Bettendorff Reaktiometer T96. Deterioration of psychomotor performance were seen in patients without amelioration of their psychopathologic symptoms, especially when treated with moclobemide. These findings were regarded as a hint that possibly the therapeutic agent interacts with the wrong transmitter system and perhaps this is the reason for the deterioration of psychomotor functions. PMID- 2587674 TI - [Hypertensive crises with reversible inhibitors of monoamine oxidases? Results of tyramine interaction studies]. AB - Healthy ambulatory subjects took 6 different MAO inhibitors (MAOIs) orally for 2 to 4 weeks. The new reversible MAO-A inhibitors brofaromine and moclobemide were compared with the irreversible MAOIs clorgyline, selegiline, phenelzine and tranylcypromine. Pressor responsiveness to oral tyramine was assessed before, during and after treatment. In unmedicated subjects, doses of tyramine to raise systolic blood pressure by at least 30 mmHg (PD30) ranged between 200 and 800 mg. During treatment with MAOIs, the PD30 decreased. The ratio of median effective doses (ED50) of tyramine (pre- vs post-treatment) was: selegiline 5, moclobemide 7, brofaromine 10, clorgyline 10, phenelzine 13 and tranylcypromine 55. Pressor responsiveness normalized within 8 days after stopping the reversible MAOIs and 30 days after tranylcypromine. The increased sensitivity after phenelzine persisted for longer than 8 weeks and after clorgyline for longer than 15 weeks. The results suggest that the two reversible MAO-A inhibitors moclobemide and brofaromine carry a much reduced liability to tyramine-related hypertensive reactions. PMID- 2587676 TI - Communication disturbances and hyperactive/conduct-disturbed behavior. AB - This study examines mother-child communication as one factor in the development of conduct-disturbed/hyperactive boys. Three groups of school-age children were compared: a group including conduct-disturbed/hyperactive boys who had a significant insult in their perinatal/developmental history; a group of conduct disturbed/hyperactive boys in whom no insult could be found; and a group of normally active/non-conduct-disturbed/hyperactive boys. It was hypothesized that disturbed communication between mother and son would be found in boys who were conduct-disturbed/hyperactive, whether or not there was a probable organic cause for their dysfunction, and this hypothesis was confirmed. In addition, it was found that the communication patterns in children who had a probable organic etiology for their disturbance were different from those found in the group lacking an organic etiology. However, both of these groups exhibited communication patterns that were more disturbed than the communication from mother to son in the normally active, non-conduct-disturbed group. PMID- 2587677 TI - Maori Elder-patient relationship as a therapeutic paradigm. AB - This paper examines the dynamics of teh psychotherapeutic relationship between a Maori Elder and Maori psychiatric patients. The functioning of an Elder was examined over a period of 9 months in a psychiatric unit. A content analysis was performed on audiovisual records of 10 interviews conducted by the Elder on five psychiatric patients. The results of this analysis were used to construct a theoretical paradigm of the Elder-Patient Transaction and to contrast it with psychodynamic psychotherapy and pastoral counseling. Distinctive features of relationship, content of the sessions and the issues of dominance and dependence are discussed, and possible mechanisms of change are mentioned. PMID- 2587678 TI - The anatomy of mental unity and volition: an alternate view. AB - The preceding paper, by Louis Tinnin, challenges us to consider that there is a brain agency responsible for mental unity, volition and consciousness, which the author labels a "governing mental system" (GMS), or "ego," and that the neural substrate for this GMS is Wernicke's Area. The primary evidence in support of this position comes from three sources: a review of brain and language development in normal and abnormal individuals (e.g., deaf children); studies of patients who have undergone corpus callosum section for intractable epilepsy; and some observations of memory processing during the intracarotid sodium amytal (Wada) procedure. Our comments address two issues. The first is an analysis of the adequacy of these three sources as evidence for Tinnin's position. The second is a description of an alternative model to account for the mental system we agree exists but do not yet understand. PMID- 2587679 TI - Delayed onset PTSD among Israeli veterans of the 1982 Lebanon War. AB - This is an exploratory study of the nature, course and rates of delayed post traumatic stress disorder (PTSD). We reviewed 150 medical files of Israeli soldiers who sought help between 6 months and 5 years after the 1982 Lebanon War. Results indicated that only 10% of the cases were truly examples of delayed PTSD; in a large proportion of the cases, help-seeking rather than onset was delayed. PMID- 2587680 TI - Brief dynamic psychotherapy: characterologic intervention and the physical position of the patient. AB - BRIEF dynamic psychotherapy has achieved widespread acceptance in the past 20 years but as yet has formed no satisfactory approach to effecting character change. The most frequently chosen path has been to select for treatment only those who readily demonstrate the capacity to investigate focal conflict, thus bypassing character armor. The strategy here flows in the opposite direction. Within brief dynamic treatment, what technical alterations might more effectively engage characterologic difficulty? I report on one such innovation. When patients are asked to sit close to but turned at 180 degrees from the therapist, those with character disorders--particularly patients suffering from mid-level disorders--can often suspend their defenses sufficiently to permit specific types of new material into the treatment. This alteration in process appears, in turn, to abet outcome. PMID- 2587681 TI - The efficacy of poetry therapy: a computerized content analysis of the death poetry of Emily Dickinson. AB - A computer content analysis of a representative sample of the death poetry of Emily Dickinson is examined in an attempt to identify its therapeutic efficacy. The findings suggest that its therapeutic value lies in an underlying theme that offers a coherent experience with death from which the reader can achieve a degree of mastery and control. PMID- 2587682 TI - U.S.A., 13 years later. AB - In October 1974, after living in Baltimore for 16 years, I went back to my home town, Belo Horizonte, in the State of Minas Gerais, Brazil. By then I was a citizen of the United States and a Board Certified Psychiatrist, and I wanted to bring back there some of what I had learned here. In 1987 I returned to the United States, and I want to set down my impressions of what has happened here since I left. PMID- 2587683 TI - Hartmann's "Ego Psychology and the Problem of Adaptation". AB - Hartmann's monograph is an argument for the problem-solving value of all aspects of the mind and for the subordination of intelligence to the organism's larger, primarily social purposes. Hartmann proposed that, in psychoanalytic treatment, intelligent reflection serves one's largest purposes by taking respectful account of non-rational but adaptive ways of appraising reality, with a view toward making the best use of non-rational as well as rational propensities. He regarded it as the kind of thinking that the sociologist, Karl Mannheim, had recommended to government planners faced with immensely complicated, incompletely masterable forces. Hartmann's view of the role of the intellect in analytic treatment suggests that therapists should maintain both their demand for intelligent reflection and their hopefulness about other kinds of work that may be going on sub rosa. PMID- 2587684 TI - On the origins of contemporary structural theory: an appreciation of "Ego Psychology and the Problem of Adaptation". AB - Hartmann's monograph was one of four works which produced a major revision of psychoanalytic theory. Following a brief summary of the monograph, this essay assesses its impact on contemporary psychoanalytic thinking. It considers some confusions about and revisions of Hartmann's ideas and explores terrain first broached in this work which has become very influential but which has not yet been fully exploited. Lastly, this essay will consider Hartmann's hope that psychoanalysis would become a general psychology. PMID- 2587685 TI - The contribution of Hartmann's adaptational theory to psychoanalysis, with special reference to regression and symptom formation. AB - My experience of clinical work is consistent with the conclusion that both practice and theory are improved by applying the contributions of Heinz Hartmann. His work provides an important conceptual bridge to understanding the adaptive and pathologic changes that appear in the course of human development. The specific details of those changes are just as much an issue demanding the analyst's attention as is the tracing of patterns of childhood instinctual life. In this paper, I will point to some areas of controversy where renewed attention to Hartmann's ideas might be useful, and I will attempt to illustrate the clinical utility of his theoretical contributions. PMID- 2587686 TI - Hartmann on adaptation: an incomparable or incomprehensible legacy? AB - Hartmann's essay sets forth ideas of incomparable value as well as incomprehensible density. While he developed many important concepts which have far-ranging clinical utility even today, his attempt to extend psychoanalysis into a general psychology back-fired because it separated psychoanalytic concepts from analytic data. Because of his lack of clinical material or anecdotal illustration, Hartmann's theoretical scaffolding has been frequently misunderstood and misapplied. This paper re-examines Hartmann's essay in light of current clinical and metapsychological issues, and illustrates some of his more important ideas. PMID- 2587687 TI - Hartmann, health, and homosexuality: some clinical aspects of "Ego Psychology and the Problem of Adaptation". AB - Hartmann's theories have experienced a remarkable rise and fall in popularity over the past fifty years. In this paper, an effort is made to arrive at a balanced view. The genetic and economic aspects of Hartmann's ego psychology are found to be problematic, but the dynamic aspect led to a sophisticated psychoanalytic concept of health as yet unsurpassed. Hartmann always called for the clinical application of his ideas. In this spirit, a vignette is offered from a clinical area in which questions of "health" and "illness" are particularly vexing at present. PMID- 2587688 TI - [Medical and psychosocial effects of methadone substitution in HIV infected substance-dependent patients]. AB - After an average observation time of 12 months we can confirm that methadone substitution on an outpatient basis has proved significantly useful for a majority of chronically intravenously opiate-dependent HIV-infected patients of the stages CDC IV or WR 3-6 if methadone is given under controlled conditions, the improvement consisting in an amelioration of certain medical and psychosocial parameters. In 25 out of 30 patients methadone substitution resulted in termination of the previously existing intravenous heroin addiction. In the further course of treatment one of these 25 patients could then be induced to undergo a methadone withdrawal course followed by long-term withdrawal therapy. Since the patients were no longer dependent on heroin, they were no longer compelled to procure it under all circumstances, so that crime and prostitution connected with the pressure to obtain heroin by all means were now superfluous. This provided the most important prerequisites for medical and social care for the patients. The decisive factors determining the effectivity of substitution and hence a successful stabilisation are the integration of the patient in a network of care including the family doctor, outpatient HIV care by a relevant clinic, drug advice centre of AIDS help, and a Public Health Office. This also guarantees that the patients act responsibly in respect of their AIDS infection. In very few patients the permanent success of the treatment was at high risk due to unsatisfactory social care, lack of social security measures, progression of the underlying disease, a too low methadone dosage level, and partnership conflicts. PMID- 2587689 TI - [The concept of developmentally-induced structural ego disorders--a reference frame for working with extremely borderline patients?]. AB - The concept of developmental-structural ego defects provides a therapeutic framework for the treatment of patients who have, in the past, largely been classified as untreatable. With emphasis on individual therapeutic treatment, this paper provides a critical introduction to the concept and discusses the applicability of this therapeutic approach for extremely lower-lower class patients: patients doubly stigmatized by psychological illness and criminality who are treated in a forensic-psychiatric clinic. PMID- 2587690 TI - [10 years' incidence of positive diagnostic decisions in functional heart disease in acute clinic treatment]. AB - An unexpected low percentage of 0.89 per thousand (43 Patients) with the diagnosis of neurocirculatory asthenia could be documented in a clinical database of 48.114 patients with representative data of diagnostic and therapeutic procedures in West German hospitals. As expected, mean manifestation age in male patients was the age group of 20 to 39 years. Only 4.1% of the neurotic patients were committed to the hospital with this diagnosis. These data document the representative diagnostic behaviour towards neurotic chest pain patients in acute hospitals and probably reveal a serious underestimation of the real prevalence. There is evidence that for these patients the diagnostic strategy is weak and distorted by some systematic bias. PMID- 2587691 TI - [Compliance of children and adolescents with type 1 diabetes (juvenile diabetes mellitus)]. AB - Compliance has a main influence on quality of metabolic control of juvenile diabetics and on prognosis in course of illness. This study examines specific problematic spheres in treatment of type-1-diabetics and tries to identify reasons for non-compliance behaviour. The study includes 60 type-1 diabetics between 10 and 16 years of age by a compliance-self-report questionnaire. Results show diet, self-control and parts of insulin-therapy to be problematic treatment components. Differential effects with regard to sex, age and duration of illness have been found. As main reasons for non-compliance, social circumstances, states of emotion, overcharge and lack of information have been identified. PMID- 2587692 TI - [Psychosocial management in pediatric oncology--presentation of a cooperative team model]. AB - This article presents a psychosocial patient-care program for pediatric cancer patients and their families. The program, initiated within the framework of a "cooperative team model", represents a new organisational form of cooperation between somatic and psychosomatic medicine that has been virtually untested in the filed of internal medicine. The advantages of this form lie in the improved availability of the families involved and the inherent possibilities of appropriate and effective assistance in overcoming the burdens of the illness and the treatment. Comparison with a liaison model showed a 3-times higher mean contact quota per patient/family. Problems which can be expected through implementation as well as related conflicts are discussed. Basic rules are formulated which must be followed if successful interdisciplinary cooperation is to be achieved. Areas of responsibility and activity are described for members of the psychosocial team (psychologists, social workers, visiting nurses) and a basis for documentation is illustrated using the evaluating results. The working concept behind an integrated psychosocial care system includes, as its basis, accompanying support to the involved families within the framework of general psychosocial care in which all of the members of the entire oncological team take part. As required, the special capabilities of the various psychosocial professions can then be brought to bear according to their functions and competence (psychosocial counselling and therapy, social-service counselling, medical and nursing care). Due to the conditions, inherent in the situation resulting from the illness and treatment, basic conceptional positions and attitudes become apparent that are of importance of psychosocial work is to be successful in a pediatric oncology ward. PMID- 2587694 TI - [Systems theory solution of the Bieri trilemma. Comments on the comments by E. G. Schmidt on my comments on the body-mind problem in psychosomatic medicine]. AB - E. G. Schmidt criticizes my critique of the wholist-emergentist solution for the mind-body problem. Against my repudiation he proposes an emergentist system theory solution apparently solving the so-called Bieri trilemma. I contend that his solution falsely introduces "psychogenic" causality into the wholist emergentistic theory. PMID- 2587693 TI - [Effect of compliance on treatment with autogenic training]. AB - Autogenic therapy courses for patient with psychosomatic psychoneurotic disorders show a high dropout rate. A study among 38 ambulant patients analysed factors of the patients have influence on their compliance. Generally the dropout group, independent of the diagnosis, shows less striking deviations. Under autogenic therapy the compliance-positive group achieves a constructive change towards normality. Realisation of autogenic therapy is achieved by patients with more intensive psychoneurotic disorders. They experience a more distinct physical answer by the basic training. It is shown that it is easier for the compliant patient to learn the autogenic therapy, which is understood as conditional response. With reference to the experience in drug compliance the results recommend that autogenic therapy should be accompanied by a compliance therapy. PMID- 2587695 TI - [Gamma-induced long-term changes in the supramolecular DNA complex of rat organs]. PMID- 2587696 TI - [The effect of fast electrons and menadione on the structural-functional status of Ehrlich ascites carcinoma cells in the early periods following irradiation]. AB - Irradiation of Ehrlich ascites tumor cells stimulates oxygen consumption, and menadione suppresses cell respiration. The combined effect of the two factors produces an additional, in comparison with the effect of menadione alone, inhibition of the rate of oxygen consumption by cells. There is an additive effect of radiation and menadione with regard to the level of cell thiols and interphase cell death. PMID- 2587697 TI - [The role of repair processes in synergism]. AB - Using a simple mathematical model of microorganism inactivation by the combined effect of two agents it was shown that repair processes lead to the synergistic increase of the damage. The latter is due to the additional nonlinearity between the response (inactivation rate constant) and the parameters of the intensity of the damage to the bioobject. PMID- 2587698 TI - [A comparative study of the micronucleus test and chromosome aberrations in PHA stimulated human lymphocytes]. AB - A dose dependence of the number of cells with chromosome aberrations was studied in PHA-stimulated donor's peripheral blood lymphocytes irradiated in vitro with doses of 10-400 cGy. In studying the number of chromosome aberrations and percentage of cells with micronuclei in parallel cultures no correlation was found between these indices within the groups exposed to a similar radiation dose. PMID- 2587700 TI - [Principles of the organization of intestinal epithelium and its recovery from damage revealed by modeling]. AB - Using the developed method of modelling the curves of the fraction of labelled indexes (FLI) in the small intestine epithelium, a relationship was found between the FLI shape and duration of the S phase and the whole generation cycle for various generations of proliferating crypt cells. On the basis of the comparison between the theoretical and experimental FLI the normal values of the generation cycles along the crypt were specified for various intestinal parts. FLI were shaped along the crypt at various time intervals after irradiation. As a result, the data were obtained on the correlation between the duration of generation cycles and their phases during the postirradiation period and for various cell generations. PMID- 2587699 TI - [The effect of high energy irradiation on the membrane potential and impulse activity of neurons in the brain of Helix pomatia]. AB - In electrophysiological experiments with a preparation of the isolated Helix pomatia brain, a study was made of the effect of pulsed irradiation with high energy electrons (20 MeV) on membrane potentials and pulse activity of "silent", pacemaking and postsynaptic neurons. It was shown that after irradiation with 150 and 300 Gy (dose rate 5 Gy/s and pulse frequency 50 Hz) "silent" neurons retain their excitability. Pacemaking neurons responded to radiation by a drastic increase in spontaneous pulse activity followed by its transfer to a clipped then to an irregular one. At the same time, the discharge frequency increased in the postsynaptic neurons. PMID- 2587701 TI - [Prevention of radiation sickness caused by low-power ionizing radiation using repeated injections of increasing doses of chemical radioprotectors]. PMID- 2587702 TI - [Radioprotective properties of a Co(III) biocomplex]. AB - In experiments with rats and mice irradiated with doses of 5 and 8.5 Gy respectively, the radioprotective properties of a coordination combination Co(III) with bioactive ligands have been investigated by the results of the hematological analysis, the indices of erythrocyte and leucocyte electric conductivity, average life, survival rate, and beta coefficient showing a probability of protecting the organism against fatal effect of ionizing radiation. The preparation has either therapeutic or protective action depending on the animal species and radiation dose. PMID- 2587703 TI - [Increase in the radiation resistance of mice using Ivastimul]. AB - A study was made of the effect of Ivastimul (IS), an aqueous extract from unicellular Chlorella algae, on the radioresistance and some haemopoiesis parameters of mice exposed to 60Co-gamma-radiation. With median and absolutely lethal radiation doses, IS was shown to produce a pronounced protective effect displayed by the increased survival rate. With sublethal doses, IS elevated the postirradiation formation of endogenous colonies and restoration of bone marrow and spleen cellularity and spleen mass. PMID- 2587704 TI - [The modifying effect of an electric current on the course of radiation injuries in animals]. AB - A simultaneous action of the modified electric current and ionizing radiation (5.5-25 Gy) was shown to decrease the death rate, to increase the life-span of rats, and to induce the intestinal syndrome at higher doses than the action of each factor delivered separately. There was a correlation between the modifying effect and the faster restoration of cellularity of bone marrow and peripheral blood, and the number of nucleate enterocytes of the small intestine mucosa. PMID- 2587705 TI - [Cumulated biological effects of microwaves and their reflection in behavior, work capacity, growth of body mass and state of brain neurons]. AB - Albino rats were exposed to 2375 mHz microwaves of 500 microW/cm2 for 169 h. At the time of exposure, the body mass growth diminished, the efficiency and vertical motor activity decreased in exposed animals in comparison with the controls. Three types of radiation-induced damages were found in the brain: chromatolysis, pyknosis, and ischemia. Different brain parts displayed different sensitivity depending on their location in relation to transverse sutures of the skull. PMID- 2587706 TI - [The morphofunctional status of the hypothalamo-hypophyseal neurosecretory system and the energy processes in the gastric tissues following electromagnetic irradiation in the millimeter wave range]. AB - A single and double 15 and 30 min exposure to electromagnetic waves of millimetric range (60 GGz, 3 mW/cm2) of a biological active point (acupuncture point) EIII36 of intact male rats and those subjected to stress inhibits the functional activity of hypothalamo-hypophysis neurosecretory system, thyroid gland and cell elements of gastric glands the inhibition being mostly pronounced in animals under stress. PMID- 2587707 TI - [Characteristics of the response of animals of different typological groups to the action of electromagnetic irradiation in the high and superhigh frequency ranges]. AB - Peculiarities in the response of male rats of various typological (e.g. high- and low-entropy) groups to the effect of electromagnetic radiation of high and superhigh frequencies have been investigated. Radiation intensity was 500 microW/cm2 and 500 V/m respectively. Animals of different entropy groups exhibited variations in the radiation response of their CNS and endocrine system as well as in the state of their offspring during the antenatal development. PMID- 2587708 TI - [Prognosis of the postirradiation radiosensitivity of mammals and man based on the criterion of LD50 following acute external irradiation]. AB - A mathematical approach is proposed to predict human sensitivity to repeated uniform irradiation by the criterion of LD50 depending on the dose of the first exposure and the time lapsed from the repeated irradiation. PMID- 2587709 TI - [Response of the developing thyroid gland of rats to a single gamma-irradiation in the period of intrauterine development]. AB - A single external exposure of pregnant rats to 2 Gy gamma-radiation caused changes in the functional status of the thyroid gland in offsprings at varying times of the postnatal development. The disturbance of the thyroid hormones balance in the blood, destruction of the thyroid gland combined with high functional tension of secretory elements, and activation of the thyrotropic function of hypophysis were revealed at remote times after irradiation. PMID- 2587710 TI - [The effect of 5-fluorouracil, metronidazole, caffeine and irradiation on the synthesis of DNA in the Pliss lymphosarcoma]. AB - Injection of 5-fluorouracil or caffeine or a combination of each of them with metronidazole removes partially or wholly the postirradiation arrest of DNA synthesis in Pliss lymphosarcoma and increases the label index and (or) the rate of its incorporation in nuclei of DNA-synthesizing cells compared to irradiated controls. The administration of the three agents arrests almost completely the DNA synthesis during the very first hours following irradiation, then prematurely removes partially the synthesis block in most DNA-synthesizing cells. PMID- 2587711 TI - [The effect of ionizing radiation on the binding of muscimol by synaptic membranes in the rat brain]. AB - A study was made of the effect of gamma-radiation on binding of muscimol, a GABA agonist, by synaptic membranes of rat brain cortex. Exposure to 2 Gy radiation was shown to reduce [3H]-muscimol binding to membranes. PMID- 2587713 TI - Changes in cellularity, CFU-S number and chromosome aberrations in bone marrow and blood of rats after neutron and continuous gamma irradiation. AB - Changes in the hematopoietic bone marrow of rats were observed after single wholebody neutron dose of 2 Gy and combined single neutron (2 Gy) and continuous gamma (6 Gy, daily dose rate of 0.5742 Gy) irradiation. Neutron irradiation significantly reduces the number of karyocytes in the bone marrow including CFU-S and induces the extensive cytogenetic damage. The following continuous gamma irradiation does not intensify the primary damage, but maintains the CFU-S and cellularity values at a decreased level for the whole time of irradiation. Recovery of the damage begins only after the termination of continuous irradiation; its course is similar to that after single neutron irradiation. The influence of combined effect of neutrons and gamma rays is nevertheless manifested in later periods after the irradiation by reduction in the total CFU-S number in the bone marrow. PMID- 2587712 TI - Effects of neutron and combined gamma irradiation of rats. AB - The effect of single neutron irradiation (2 Gy) alone and combined with continuous gamma irradiation (6 Gy accumulated during 10.5 days) was studied on the survival of rats and on nucleic acids both in the lymphoid organs and testes. After neutron irradiation alone the most profound changes in lymphoid organs and testes were found on the third and within the days 28-60, respectively. Regeneration has been undergone at a relatively fast rate. Continuous irradiation subsequent to neutron irradiation deepened only slightly the extent of the initial changes. The effect of combined irradiation manifested mainly a later times in marked slowing down of regeneration. PMID- 2587714 TI - [Changes of the cytogenetic effectiveness of the therapeutic ray of fast neutrons in water phantoms]. AB - Changes of cytogenetic effectiveness of the therapeutic ray of fast neutrons were studied in water phantom in the Medical-Biological Complex of CyclotronU-120 at the Institute for Nuclear Research of the Academy of Sciences of the Ukrainian SSR. Investigations were done in a culture of lymphocytes of the peripheral human blood by means of metaphase method to find out chromosomal aberrations. The neutrons were generated by firing a thick beryllium target with a 13.6 MeV deuteron ray in the nuclear reaction 9Be (d,n) 10B. The investigated dose range was 25-220 cGy. The results of the studies demonstrate that the cytogenetic effectiveness of radiation is reduced with increasing depth of the water phantom. The maximum reduction of the effect was seen in a depth up to 6 cm, which is attached to absorption of low-energetic neutron fraction. The obtained results confirm necessity of to filter the therapeutically applicable beam of neutron radiation. PMID- 2587715 TI - [Autopsy results in surgical-radiotherapeutic treatment of bladder carcinoma- conclusions for optimal radiologic therapy]. AB - With 282 autopsied patients with bladder carcinoma, that were treated by combined operation and radiotherapy, conclusions are given for tendency in tumor spreading as well as for complications and late-effects of radiotherapy. In 24.5% of the cases tumor tissue was found within the bladder and in 30.5% of the cases within the minor pelvis. Metastases were found in 24.1% in iliac lymph-nodes, in 21.3% of the autopsy cases in abdominal lymph-nodes. Liver, lungs, bones, and kidneys are main organs for hematological metastasizing. Little or undifferentiated carcinomas and squamous cell carcinomas show a greater tendency to metastasize than highly and medium-differentiated ureteral carcinomas. The least radiotherapeutical complications and late-effects were found in a fractionation with daily 1.5 Gy and a total dose of 60 Gy (necrotising urocystitis 17.9%, proctitis 3.6%). PMID- 2587716 TI - [Percutaneous radiotherapy for thyroid gland carcinoma]. AB - Prognostically relevant factors as well as indications for percutaneous radiotherapy are analysed by the hand of a retrospective analysis of therapeutic results in 86 patients that were exposed a percutaneous radiotherapy because of a thyroid carcinoma at the Clinic and Policlinic of the Medical Academy Erfurt during the period 1972 to 1982. The 5-years-survivals of 83% for patients with differentiated carcinoma and 22% for patients with dedifferentiated carcinoma prove the influence of tumor histology on prognosis of the disease. Next to it the locoregional tumor spreading at beginning of therapy rendered prognostically relevant. The 5-years-survival was 83% in tumor stages T1-3N0M0. With metastatic infiltration into lymph-nodes of the neck the 5-years-survival decreased to 57%, with spreading of the primary tumor beyond organ borders to 23.5%. The postoperative percutaneous radiotherapy should be applied in all cases of metastatic infiltration of lymph-nodes. In large, inoperable tumors the percutaneous radiotherapy is the solely possible palliative measure that should be applied both in differentiated and also in anaplastic carcinomas in spite of infaust prognosis. PMID- 2587717 TI - [The therapy of endometrial carcinoma with the high-dose-rate selectron]. AB - A method of brachytherapy of endometrial carcinoma is described by means of high dose-rate-afterloading technique. It is based on introducing bent probes into the right and left angle of tubes alternately. The optimal dose distribution is calculated by computer-controlled planning system. 40 Gy are applied in 4 fractions with a three-day interval. The survival, free of relapses, is 88% in stage I. The method is used by way of preoperative brachytherapy too, in which the histological examination gave no cancerous cells in 58% of the postoperative material. Only in 3% of all cases slight radioreactions occurred, in 0.3% heavy complications. The method guarantees a high comfort in treatment, so out-patients can be treated too. PMID- 2587718 TI - Cardiopulmonary imaging. PMID- 2587719 TI - [Gadolinium-DTPA as an oral contrast medium in magnetic resonance tomography]. AB - 80 patients with tumorous or inflammatory abdominal diseases were investigated with the paramagnetic MRT contrast medium Gadolinium-DTPA (Gd-DTPA, 1 mM, 15 g/l mannitol, 6-16 ml per kg body weight) at 0.5 Tesla with T1-, proton density and T2-weighted SE- and gradient-echo sequences. 53 patients were investigated also before the contrast medium was given. Gd-DTPA showed hyperintense labelling of the intestinal loops that was detectable with all excitation sequences and was constant over all phases of the passage. In 35 of the 53 patients investigated before and after application of Gd-DTPA lesions were better imaged while diagnostic improvements, especially for smaller lesions, were achieved in 5 of 80 patients. One third of the patients reported slight meteorism and diarrhoea after the mannitol-containing suspension. PMID- 2587720 TI - [An intra- and interobserver study of the accuracy of dynamic CT of hepatic space occupying lesions]. AB - An intra- and interobserver study with 10 physicians was undertaken in order to determine the accuracy of differentiation regarding the type and benign/malignant of hepatic space-occupying processes. By "conditioning" of the observers a significant reduction of doubtful cases with a slight increase in diagnostic accuracy (10% in differentiating of benign/malignant and 5% of the type) relative to our first study was achieved. Marked increases were found for 3 little experienced observers. By informing the observers on the diagnostic criteria for hepatocellular carcinoma the percentage of correct decisions was significantly increased. PMID- 2587721 TI - [Computed tomographic false diagnoses in acute pancreatitis]. AB - With computed tomography acute pancreatitis can be differentiated into an oedematous, serous-exudative, hemorrhagic-necrotizing, suppurative-abscessing and a postacute necrotizing form with high diagnostic accuracy (83.2%). Problems occur in distinguishing necrotizing from abscessing pancreatitis. False negative and false positive errors are less frequent in detecting necrosis and its differentiation from less serious forms (4.4% and 2.1%). Dynamic CT discovers also parenchyma losses not detectable without contrast medium and allows to prove subtotal or total necrosis in case of discrete changes in the native scans. Sonographic tomography contributes to diagnostics by proving acute necrotizing pancreatitis due to a chronic inflammatory pancreatic process. PMID- 2587722 TI - [Computed tomography of recurrent rectal cancer with reference to guided fine needle biopsy]. AB - Computed tomography as a non-invasive imaging method is of high sensitivity and specificity for the detection and the extent diagnosis of recurrent rectal carcinomas. CT-guided fine-needle-biopsy can be necessary to prove presacral masses, before appropriate therapeutic decisions can be done. In our material CT guided FNB showed an accuracy of 78% in 27 of 35 patients. Possibilities and limitations of the method are described. PMID- 2587723 TI - [Endoscopic-radiologic diagnosis and therapy of the bile ducts. Results of endoscopic papillotomy]. AB - Endoscopic-radiologic methods for demonstrating the hepatobiliary and pancreatic ducts are an integrated part of the diagnostic spectrum of gastroenterologic centers. At the Charite since 1975 we have made more than 5,500 endoscopic retrograde cholangio-pancreaticographies (ERCP's). This method provides immediately or later an adequate therapy as an alternative to the otherwise necessary surgery. The most frequently used and basic method is endoscopic papillotomy (EPT). In most cases it precedes endoscopic removal of concrements, prosthetic drainage of biliary pathways or extracorporal shockwave lithotripsy (ESWL). Since 1977 we have carried out 2,050 EPT's at the Charite, more than 60% of these for patients of higher age (above 60). With 98.3% successful interventions complications were seen in only 4.7% of the cases. The influence of close interdisciplinary cooperation of endoscopicists and radiologists on the results of the investigation and the rate of complications is discussed. PMID- 2587724 TI - [Changing trends in percutaneous and endoscopic bile duct drainage]. AB - Analysis of 1,104 non-surgical biliary drainages (600 ERCD, 531 PTCD) from 1983 to 1988 concerning changing frequency, indications and success rates. With a continuous increase of the total numbers, the fraction of percutaneous transhepatic drainages has decreased to 28%. With increasing degree of difficulty and risk PTCD (90.9% success) is indicated primarily in case of impossible ERCD (85.9% success) and hilar benign and malign biliary obstruction for temporary or permanent biliary drainage. Both methods are complementary and are increasingly used for combined palliative drainage. PMID- 2587725 TI - [Embolization therapy using detachable balloons]. AB - Report on the application of a new (valve equipped) detachable balloon for percutaneous transvasal embolization therapy in 372 patients with (noncerebral) curative preoperative and palliative indications. PMID- 2587727 TI - Computed radiography: photostimulable phosphor image plate technology. AB - Computed radiography is emerging as a digital imaging modality for use in conventional radiography. It is based on photostimulable phosphor image plate technology. The image plate (IP) is housed in a cassette similar to a standard radiographic cassette. The IP phosphor retains a latent image of the energy pattern to which it was exposed. This latent image is "read" as it is released from the phosphor by laser light exposure. The image is laser printed on 10 in x 14 in film. PMID- 2587728 TI - CT technologist to MRI technologist: making the transition. AB - The advent of magnetic resonance imaging (MRI) has thrust CT technologists into an exciting new phase of diagnostic imaging. The move from CT to MRI for technologists seems a logical one; however, the transition brings a variety of challenges that can make the change less than ideal. PMID- 2587726 TI - [MRT of the knee joint cartilage using 3D volume imaging in combination with a fast image processor]. AB - From the knees of healthy persons and cadavers 2D-spin-echo-sequences were compared to 3D-gradient-echo-sequences (FLASH, FISP). We were able to show that 3D-volume-imaging, combined with image processing on a fast computer, is superior to 2D-spin-echo-imaging. The advantages are: slice thickness lower than 1 mm, secondary reconstruction in any desired plane, good contrast between intraarticular fluid, the meniscus and the hyaline cartilage. For the practical application of 3D-volume-imaging resulting in multiple images the secondary reconstruction and post processing of the large numbers of images with an image processing computer is necessary. PMID- 2587729 TI - Statistical evaluation of admission criteria for a radiography program. AB - The admission process of a radiography program was analyzed. The criteria used were summarized in a weighted score. A measurable difference was found between applicants offered appointment and those not, and the weighted score was found to be a statistically significant predictor of subsequent student performance. PMID- 2587730 TI - How accountable are you? PMID- 2587731 TI - Test statistics. PMID- 2587733 TI - [2-dimensional CT arthrotomography in the postoperative follow-up of a new anterior cruciate ligament plasty]. AB - Fifty-eight patients underwent intraarticular reconstruction of the anterior cruciate ligament. This was performed by using an autogenous transplant from the mid portion of the patellar ligament with a proximal and distal bone block, as described by Hertel. For comparison with the conventional X-ray examination, HRCT was performed to study the early postoperative results. In four patients (7%) dislocation of the bone block in the femoral condyle was seen. Two-dimensional reconstruction proved to be a satisfactory method for demonstration of the exact position of the autogenous transplant in both coronary and sagittal planes. PMID- 2587732 TI - kVp cassette measurements. PMID- 2587734 TI - [MRT of the status following augmentation plasty of the anterior cruciate ligament using carbon fibers]. AB - In 19 patients treated with carbon-fiber ligament augmentation for the anterior cruciate ligament, the clinical findings were compared via MRI. Visualization of the intra- and extra-articular portion of the graft was possible in 84%. The integrity of the ligaments was be shown in an equal percentage. Thus, MRI is a useful diagnostic tool for non-invasive imaging for repeated follow-ups in patients with carbon-fiber ligament augmentation. PMID- 2587735 TI - [Fractures accompanied by injuries of the great vessels in sport and leisure accidents. Diagnosis and management concept]. AB - Extremity fractures with concomitant vascular injuries are surgical emergencies. Especially injuries of the upper extremities require a preoperative angiographic examination for the localization of the vascular lesion. In vascular lesions of the lower extremities a primary angiography is not necessary, if there is an opportunity for an intraoperative radiologic evaluation. In our traumatological department 104 patients were treated over the last 15 years with that combined injury. The concept of immediate stabilization of the fracture with simultaneous or postponed arterial repair has been proved to be appropriate. The fasciotomy as prophylactic procedure of a postischemic compartment syndrome is also a part of our concept during the last years. The late results in our mostly young patients depended on the degree of soft tissue damage and the time of ischemia. The often untreatable nerve lesions contributed to a loss of use of about 30% in the late courses. PMID- 2587736 TI - [An unclear process in CT of the liver. Caroli syndrome]. PMID- 2587737 TI - Alpha-bungarotoxin receptors in the CNS. PMID- 2587738 TI - Nicotinic acetylcholine receptor diversity: agonist binding and functional potency. PMID- 2587739 TI - Properties of putative nicotine receptors identified on cultured cortical neurons. AB - Cultured cortical neurons derived from fetal rat brain contain putative high affinity nicotinic receptors. Cortical glial cells do not contain any high affinity binding sites for nicotine. The affinity, kinetic binding properties and pharmacological specificity of neuronal sites are the same as those determined for adult brain tissue. However, the number of sites in cultured neurons is lower than in adult cortex. Cultured cortical neurons appear to be a suitable model system for defining the location(s) and functional properties of high-affinity nicotinic receptors in mammalian brain. PMID- 2587740 TI - Chronic nicotine exposure and brain nicotinic receptors--influence of genetic factors. PMID- 2587741 TI - Effect of nicotine on the release of acetylcholine and amino acids in the brain. PMID- 2587742 TI - Regulation by nicotine of midbrain dopamine neurons. PMID- 2587743 TI - Nicotine and opioid peptides. PMID- 2587744 TI - Differential brain and peripheral nicotinic regulation of sympathoadrenal secretion. PMID- 2587745 TI - Nicotine-induced tolerance and dependence in rats and mice: studies involving schedule-controlled behavior. AB - Tolerance to nicotine's disruptive effects on operant responding develops rapidly over a 14-36 day repeated dosing period in both rats and mice. This occurred regardless of whether nicotine was administered pre- or post- to each behavioral exposure. Thus, tolerance development appeared to depend on both behavioral as well as pharmacological mechanisms. It is suggested that the pharmacological mechanism(s) involved in the development of tolerance may be related to an up regulation of brain area nicotinic receptors. As observed with receptor binding studies, mecamylamine did not appear to attenuate the development of pharmacological tolerance to nicotine (does not attenuate nicotinic receptor up regulation) even though this cholinergic antagonist will antagonize nicotine's acute behavioral disruptive effects completely. However, the fact that mecamylamine may induce some cross-tolerance to nicotine does complicate our interpretation of these data. The development of nicotine tolerance, in part, appears to depend upon an interaction at some acetylcholine-sensitive nicotinic receptor as evidenced by the ability of physostigmine to induce cross-tolerance to nicotine in both the rat and mouse. These data support the view that nicotine may be inducing its effects via at least two separate nicotinic receptors, one of which may be acetylcholine sensitive. Furthermore, binding data suggest that physostigmine's effects were related to a reduction of available central nicotinic receptor sites. In contrast to what humans experience, the rat does not appear as sensitive to nicotine-induced physical dependence, at least when operant behavior is utilized as the dependent variable used to measure withdrawal signs. Other approaches such as drug discrimination and conditioned avoidance paradigms may provide a better alternative to the evaluation of nicotine-induced dependence. Research utilizing schedule-controlled behavior in the mouse, on the other hand, has provided us with an additional model of a nicotine-induced withdrawal syndrome which may be of value in evaluating mechanisms of nicotine dependence. However, as with all of these findings, much work is needed to confirm and further characterize each model in so far as they may provide us with a reliable and specific measure of nicotine dependence. PMID- 2587746 TI - Protective effects of chronic nicotine treatment on lesioned nigrostriatal dopamine neurons in the male rat. AB - The present results demonstrate that chronic nicotine treatment can in part protect against mechanically-induced and neurotoxin-induced degeneration of nigrostriatal DA neurons. These results indicate that in sufficient doses chronic treatment with nicotine may be considered in the pharmacological treatment of Parkinson's disease. It remains to be demonstrated whether these protective actions can be extended to include also other injured neurons such as the cholinergic neurons, known to be severely affected in Alzheimer's disease. PMID- 2587747 TI - Structure and function of neuronal nicotinic acetylcholine receptors deduced from cDNA clones. PMID- 2587748 TI - Nicotine dependence and tolerance in man: pharmacokinetic and pharmacodynamic investigations. PMID- 2587749 TI - Attempts to visualize nicotinic receptors in the brain of monkey and man by positron emission tomography. PMID- 2587750 TI - Stereoselectivity of nicotinic receptors. PMID- 2587751 TI - [Molecular functions of cytoskeletons]. PMID- 2587752 TI - [Identification of functional domains in beta-tubulin molecule by molecular biological methods]. PMID- 2587753 TI - [Dynamic assembly and disassembly of microtubules]. PMID- 2587754 TI - [Regulation of the assembly-disassembly of intermediate filaments]. PMID- 2587755 TI - [In vitro actin-myosin motility assay system]. PMID- 2587756 TI - [Structure and function of stress fibers]. PMID- 2587757 TI - [Structures and functions of protozoan actins]. PMID- 2587758 TI - [Adherens junction: its structure and function]. PMID- 2587759 TI - [Regulation of mitogenic signal transduction by microtubules]. PMID- 2587760 TI - [Ca2+-dependent phosphorylation of cytoskeleton proteins and its pharmacological control]. PMID- 2587761 TI - [Abnormality in the cytoskeleton of cancer cells--with special reference to intermediate filaments]. PMID- 2587762 TI - [Protein molecules constituting centrosome and their function]. PMID- 2587764 TI - [Dynamics of protein molecules in the cytoskeleton of the dividing cell]. PMID- 2587763 TI - [Effect of hexylene glycol on microtubular structures in starfish oocytes and sea urchin eggs]. PMID- 2587766 TI - [The cytoskeleton in cytokinesis in plant cells]. PMID- 2587765 TI - [Molecular architecture of mitotic apparatus]. PMID- 2587767 TI - [Mechanism of cytokinesis: isolation and properties of cleavage furrow]. PMID- 2587768 TI - [Organization of cytoskeletal proteins in slow axonal transport]. PMID- 2587769 TI - [Cytoskeleton and translocation of cytoplasm in plant cells]. PMID- 2587770 TI - [Cell polarity and cytoskeleton]. PMID- 2587771 TI - [Roles of microfilaments and microtubules in morphogenesis of multicellular animals]. PMID- 2587772 TI - [Current alexithymia research. Critical comments on the "instrumentalizing" critique]. AB - Referring to the paradigms of newly developed tests, split-brain research, and modern treatment strategies, Hoppe argues that Ahren's critique (1988) of research on alexithymia is onesided because it ignores incompatible research findings. PMID- 2587774 TI - [Hypertension as a medical and social problem]. PMID- 2587773 TI - [Institutionalization of psychoanalysis by health policy. The "general practice study" and its "short form"]. AB - The author reviews the "study of practice" concerning the delivery of psychotherapeutic services in the Federal Republic. She then evaluates the short formulation of these findings and finally the long version as well. In doing so, she traces developmental tendencies of psychoanalysis in the Federal Republic. PMID- 2587775 TI - [Hypertension in pregnancy]. PMID- 2587776 TI - [Arterial hypertension in children and adolescents]. PMID- 2587777 TI - [New look at old and new hypotensive drugs]. PMID- 2587778 TI - [Is the problem of using alkalizing drugs only medical history?]. PMID- 2587779 TI - [Symposium--"Lipids, lipoproteins and arteriosclerosis". 19-20 May 1988. Proceedings]. PMID- 2587780 TI - [Strategies in studying lipids in the light of progress in arteriosclerosis research]. PMID- 2587781 TI - Special investigations on the differential diagnosis of FAT metabolism disorders. PMID- 2587782 TI - Actual situation in the field of standardization of methods for the determination of lipid parameters. PMID- 2587783 TI - Standardization of diagnostic laboratory methods--results, experiences and future goals. PMID- 2587784 TI - [Value of studying lipids in the prevention of cerebrovascular disorders]. PMID- 2587785 TI - The clinical diagnostic significance of the investigation of receptor mediated pathway of LDL. AB - Some types of LDL-receptor investigations have been demonstrated which can also be carried out in routine clinical laboratory. Special attention has been layed on the testing of lymphocytes and monocytes which are available easier than tissue samples but, which are, however, according to our experiences appropriate for the LDL receptor analysis. PMID- 2587786 TI - Hypertriglyceridemia--independent risk factor or risk marker? PMID- 2587787 TI - Apolipoproteins as risk indicators of ischemic heart disease. AB - About 50% of the individuals with a coronary risk show lipid levels within the normal range. Therefore, apolipoprotein profiles could be better risk indicators than TC or TG. Apolipoproteins generally discussed in this context are apo A1, apo B, and apo E. Their diagnostic validity, however, is ambigously evaluated. The individual iso-protein pattern of apo E is important for the differential diagnosis of the type III hyperlipidemia with its strong predisposition for premature atherosclerosis. Moreover, the extent of the apo E sialylation seems to be important because the modification of apo E by sialic acid alters its metabolism. Our date provide evidence that in IDDM and NIDDM the degree of apo E sialylation is increased. Concerning apo A1 and B we tried to find out parameters suitable for the prediction of the coronary risk both in the hyperlipidemic and the normolipidemic state. 64 male survivors of a myocardial infarc"ion and 60 matched controls were included in the study (group I). From group I a supopulation showing non-pathological values for TC and TG was selected (group II with 31 survivors and 44 controls). The diagnostic validity of the parameters apo A1, apo B, TC, HDL-C, apo A1/apo B, TC/apo B, HDL-C/apo B, TG, TG/apo A1, TG/HDL C, TC-HDL-C/apo B determined by calculation of their sensitivities, specificities, efficiencies, and predictive values. Only the parameters TC/apo B, HDL-C/apo B, and apo B were suitable in the order given for detection of the coronary risk. Using the TC/apo B ratio 71-76% of the controls and 79% of the survivors could be exactly reclassified independent of the group they belonged to.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2587788 TI - [Serum lipoprotein level and coronary disease]. PMID- 2587789 TI - Lipids and lipoproteins as risk indicators for coronary heart disease (a study on male patients with defined vessel findings). PMID- 2587790 TI - Interrelationship between metabolism of lipids and glucose. PMID- 2587791 TI - [Effect of dietary fats and cholesterol on lipoprotein metabolism]. PMID- 2587792 TI - [Studies on blood lipids in medical procedures]. PMID- 2587793 TI - Psychometric functions for the discrimination of differences in intensity of Gaussian noise. AB - A new theory of sensory functioning by Laming predicts how the shape of the psychometric function depends on the context in which a signal is presented. The discrimination of intensities of noise was therefore studied with four different stimulus configurations. In one, observers discriminated between two separate noise samples that differed in intensity. In accordance with the theory, a normal probability integral provided a better fit to each observer's data than either of two other functions: a normal integral with respect to the square of the difference, or a normal integral with respect to the fourth power of the difference. In a second task, observers detected an increment in a continuous noise. For eight out of nine sets of data, a square-law function provided a better fit than either a normal integral or fourth-power function. A third task asked observers to decide which of two noises was amplitude modulated. The predicted square-law function provided the best fit for four out of five observers. In a fourth task, one observer detected an interval of amplitude modulation in a continuous noise. As predicted by the theory, a fourth-power function provided the best fit. In addition, Weber fractions for difference discriminations decreased approximately with the square root of sample duration for durations up to 300 msec, whereas Weber fractions for increment detections decreased approximately directly with duration for durations up to 100 msec. The results are usually in qualitative agreement with the theory and often in quantitative agreement as well. PMID- 2587794 TI - Modelling visual detection: luminance response non-linearity and internal noise. AB - Two experiments that investigate the effect of various display factors on the detectability of a thin line signal in random visual noise are described. Three statistical decision models are described, together with their ability to account for the results. The first is an "ideal detector" model, the second an "energy integrator" model, and the third a model based upon the operation of retinal ganglion cells which incorporates a gain control mechanism. The ideal detector model fails to give a good account of human performance, whereas the other two models provide a good fit to the data. The digital Laplacian with gain control model has the slight advantage over the energy integrating model in being able to account for a small superiority in the detection of dark as opposed to bright signals. Finally, both models require the inclusion of an estimate of the internal noise of the human visual system to account for the pattern of performance observed under changing conditions of display contrast. PMID- 2587795 TI - The appearance of surfaces specified by motion parallax and binocular disparity. AB - The experiments reported in this paper were designed to investigate how depth information from binocular disparity and motion parallax cues is integrated in the human visual system. Observers viewed simulated 3-D corrugated surfaces that translated to and fro across their line of sight. The depth of the corrugations was specified by either motion parallax, or binocular disparities, or some combination of the two. The amount of perceived depth in the corrugations was measured using a matching technique. A monocularly viewed surface specified by parallax alone was seen as a rigid, corrugated surface translating along a fronto parallel path. The perceived depth of the corrugations increased monotonically with the amount of parallax motion, just as if observers were viewing an equivalent real surface that produced the same parallax transformation. With binocular viewing and zero disparities between the images seen by the two eyes, the perceived depth was only about half of that predicted by the monocular cue. In addition, this binocularly viewed surface appeared to rotate about a vertical axis as it translated to and fro. With other combinations of motion parallax and binocular disparity, parallax only affected the perceived depth when the disparity gradients of the corrugations were shallow. The discrepancy between the parallax and disparity signals was typically resolved by an apparent rotation of the surface as it translated to and fro. The results are consistent with the idea that the visual system attempts to minimize the discrepancies between (1) the depth signalled by disparity and that required by a particular interpretation of the parallax transformation and (2) the amount of rotation required by that interpretation and the amount of rotation signalled by other cues in the display. PMID- 2587797 TI - Spatial cueing and the relation between the accuracy of "where" and "what" decisions in visual search. AB - To study the processes underlying selective attention in visual search, the relation between the accuracy of "where" (location) and "what" (same/different orientation matching) decisions was analysed under various display conditions. Target-non-target discriminability was varied by contrasting single and multiple element displays; further, attention was directly manipulated by spatial cueing. In Experiment 1, analyses for both single and multiple displays showed that localization accuracy remained above chance when same/different matching failed; the inverse also obtained. It seems that accurate matching is not a prerequisite for target localization, nor is accurate localization a prerequisite for same/different matching. However, localization is a prerequisite for the accurate recognition of target orientation (Experiment 2). In this case, it seems that features critical for localization "call" attention to a particular candidate location. This facilitates further (shape) analysis of the stimulus that is found there. This orienting process is by-passed if attention is cued to the location in advance. PMID- 2587796 TI - Attention effects on form discrimination at different eccentricities. AB - Considerable disagreement exists in the visual attention literature about how attention is allocated over the visual field. One frequently expressed metaphor is that attention moves like a spotlight, and in some variants it is assumed that attention takes longer to shift to targets further from fixation. In order to test this metaphor, five experiments were conducted in which target location was precued and form discrimination accuracy was assessed. By varying the interval between the precue and the target (stimulus onset asynchrony, SOA), a time course of attention effects was obtained for targets at 2 degrees, 6 degrees, and 10 degrees eccentricity. In the first three experiments, precueing effects were found, but there were no differences in performance as a function of eccentricity for very short SOAs, with either a peripheral cue or a foveal arrow cue. For long SOAs, however, performance was better for targets that were closer to fixation. In Experiments 4 (peripheral cue) and 5 (foveal cue), the targets were scaled to make them equally discriminable at all eccentricities. Again precueing effects were found, but there were no differences in accuracy as a function of eccentricity for most SOAs. These results suggest that attention shifting is not analogous to a constant-velocity moving spotlight. PMID- 2587798 TI - Varieties of object constancy. AB - Three experiments are described in which two pictures of isolated man-made objects were presented in succession. The subjects' task was to decide, as rapidly as possible, whether the two pictured objects had the same name. With a stimulus-onset asynchrony (SOA) of above 200 msec two types of facilitation were observed: (1) the response latency was reduced if the pictures showed the same object, even though seen from different viewpoints (object benefit); (2) decision time was reduced further if the pictures showed the same object from the same angle of view (viewpoint benefit). These facilitation effects were not affected by projecting the pictures to different retinal locations. Significant benefits of both types were also obtained when the projected images differed in size. However, in these circumstances there was a small but significant performance decrement in matching two similar views of a single object, but not if the views were different. Conversely, the object benefit, but not the viewpoint benefit, was reduced when the SOA was only 100 msec. The data suggest the existence of (at least) two different visual codes, one non-retinotopic but viewer-centred, the other object-centred. PMID- 2587799 TI - The effects of surface detail on object categorization and naming. AB - Three experiments are reported examining the effects of surface colour and brightness/texture gradients (photographic detail) on object classification and naming. Objects were drawn from classes with either structurally similar or structurally dissimilar exemplars. In Experiment 1a, object naming was facilitated by both congruent surface colour and photographic detail, with the effects of these two variables combining under-additively. In addition incongruent colour disrupted naming accuracy. These effects tended to be larger on objects from structurally similar classes than on objects from structurally dissimilar classes. Experiment 1b examined superordinate classification. There were again advantages due to congruent colour and photographic detail on responses to objects from both structurally similar and structurally dissimilar classes. Incongruent colour disrupted classification accuracy on structurally distinct but not structurally similar items. For structurally similar items, the advantages of congruent surface attributes on classification were smaller than on naming, but this was not the case for structurally dissimilar items. Experiment 2 examined subordinate classification of structurally similar objects. Now effects of congruent and incongruent colour, but not of photographic detail, were found. Experiment 3 showed that congruent and incongruent colour effects occur only when the colours occupy the internal surfaces of objects. The results suggest that surface details can affect object recognition and naming, depending upon: (1) the degree to which objects must be differentiated for a correct response to be made, and (2) the nature of the rate-limiting process determining performance. PMID- 2587800 TI - Spreading activation in episodic memory: further evidence for age independence. AB - Seventy-two young (mean age = 25 years) and 72 old adults (mean age = 71 years) participated in an experiment that addressed the influence of episodic and semantic prime activation on speeded episodic recognition judgements. On each test block, subjects studied two paragraphs at their own pace to achieve a designated level of episodic recognition performance. Following the study period, subjects were presented a series of prime-target trials for speeded episodic recognition. The primes were either (a) episodically related to the target, (b) semantically related to the target, (c) episodically and semantically related to the target, or (d) episodically and semantically unrelated to the target. The stimulus onset asynchrony (SOA) between the primes and targets was either 200 msec, 600 msec, or 1000 msec to address age-related changes in the rate at which these different prime types influenced performance. The results indicated that, compared to young adults, the old adults (a) studied the paragraphs for a longer period of time, (b) responded to the targets more slowly, and (c) were less accurate in their episodic recognition decisions. Although there were these main effects of age, the young and old adults were influenced in a similar fashion by the different prime-target relationships and by the interactive influences of the prime-target relationships and SOA. Correlational analyses indicated that the pattern of priming effects was as similar across the two age groups as across two pseudo-groups that were matched on the age dimension. These results were viewed as further support for the notion that the characteristics of the spreading activation mechanism as reflected by prime-target manipulations are relatively stable across young and old adults. PMID- 2587801 TI - Perinephric xanthogranulomatous pyelonephritis simulating a renal or retroperitoneal tumor on X-ray CT and angiography. AB - A case of perinephric xanthogranulomatous pyelonephritis is presented. Ultrasonography and X-ray computed tomography (X-CT) showed a mass on the posterior aspect of the right kidney, causing us to suspect right renal cell carcinoma. Pyelography showed a deformity of the right renal calyces. From angiographic results, we considered the possibility of hypovascular renal cell carcinoma, subcapsular tumor, or retroperitoneal tumor. The mass was diagnosed pathologically as perinephric xanthogranulomatous pyelonephritis. PMID- 2587802 TI - Gallium-67 citrate scintigraphy in Wegener's granulomatosis involving the stomach. AB - 67Ga-citrate scintigraphy was performed on a 68-year-old woman with Wegener's granulomatosis of the right orbita and nasal cavity to search for other involved sites. Seventy-two-hour images demonstrated an abnormal accumulation on the left upper abdomen, in addition to her head and chest. Upper gastrointestinal series revealed marked deformation of the upper part of the stomach and a large shallow ulcer on its posterior wall. The histological diagnosis from biopsied specimens on gastroendoscopy was an involvement of Wegener's granulomatosis. 67Ga-citrate scintigraphy was helpful in detecting the sites of involvements of this disease. PMID- 2587803 TI - Mycotic aneurysm. AB - Mycotic aneurysms must be diagnosed rapidly because of the high mortality, associated with them. X-ray computed tomography (X-CT) is a noninvasive modality. Intravenous digital subtraction angiography (IVDSA) is also much less invasive and less dangerous than arteriography, especially in mycotic aneurysms, whose wall is thin. We describe two patients with mycotic aneurysms diagnosed by X-CT and IVDSA. PMID- 2587804 TI - The optimum Butterworth-Wiener filter for I-123 IMP brain SPECT. AB - The optimum Butterworth-Wiener filter (BWF) for the preprocessing of N-isopropyl p-[I-123]-iodoamphetamine (I-123 IMP) SPECT was determined by a simulation experiment. Sixty-four images of the brain phantom containing 14.8 MBq of I-123 IMP were collected with a gamma camera equipped with a slant hole collimator during a 360-degree rotation. The images were processed with 27 BWFs of different shapes, followed by SPECT image reconstruction and visual comparison. The optimum BWF had a cutoff frequency of 0.25/pixel, FWHM of four pixels, and constant of 0.05. The image quality was greatly affected by the cutoff frequency of BWF used for preprocessing. PMID- 2587805 TI - Construction of a laser transmission photo-scanner: pre-clinical investigation (report 2). AB - A prototype high-speed laser transmission photo-scanner using a 1 mm He-Ne laser beam and corresponding detector was constructed. Signals obtained from the detector were digitalized and stored in floppy disks by a micro-computer and displayed as color-coded pictures on the CRT monitor. The data were analyzed and absorption in the tissue was shown in a histogram. Breast tissue was simulated using pork, ham, lard, and cheese in a pre-clinical investigation. Normal breasts of volunteers were also examined. When disks of varying sizes were inserted into ham and cheese of various thicknesses, it was found that disks closer to the beam's point of entrance produced the best images, while disks in the center and those closer to the exit were poorly detected. Disks close to the surface were better detected than central lesions. Laser transmission images of normal breasts of twelve volunteers were symmetrical but often nonhomogeneous because of the complexity of breast tissue. PMID- 2587806 TI - Radiotherapy of dural arteriovenous malformation in the cavernous sinus. AB - Six patients with dural arteriovenous malformation (DAVM) in the cavernous sinus were treated by irradiation. The region of the abnormal vascular network was irradiated with a 10 MV linear accelerator; the total dose given ranged from 3,200 to 5,100 cGy (150-200 cGy per day, 750-1,000 cGy per week). All patients responded favorably to the treatment, with three of the six having no residual symptoms or signs of disease. Postradiotherapy angiography confirmed the complete disappearance of the shunts in two of the three patients. No significant side effects were observed during the follow-up period, which ranged from 10 months to four years. Radiotherapy is considered to be a useful treatment method for DAVM, especially for those patients having shunts from the meningeal branches of the internal carotid artery. PMID- 2587807 TI - Cosmetic evaluation of breast conserving treatment for mammary cancer. 1. Proposal of a quantitative scoring system. AB - In a population of 142 patients with stage I and II breast cancer, treated with tumor excision and external radiotherapy, using a wide range of radiation doses and fractionation schedules, an attempt was made to quantify the cosmetic outcome. Quantitative measurements of nipple displacement and breast contour retraction were compared and correlated with qualitative scoring by a panel. In the vast majority, the quantitative assessments correlate very well with subjective, qualitative scoring, making this method relevant for clinical use. There are a few exceptions, mainly cases where localized skin changes such as severe telangiectasia or skin necrosis affect strongly the cosmetic result but can go undetected in this measuring system. Also limited surgical deformations, which can detract seriously from cosmetic success, particularly when they occur in the medio inferior quadrants, can not always be assessed by this method. The routine use of these measurements in clinical practice is very simple. Only one photograph, taken in standard conditions is needed. Measurements can be carried out quickly, using the plotting device of a treatment planning system. This system may be of great use for follow-up of new treatment modalities and the study of the development of radiation fibrosis in breast cancer. PMID- 2587808 TI - Clinical radiobiology of malignant melanoma. AB - Tumor-control probability (TCP) was analyzed in a series of 121 patients having 239 histologically proven recurrent or metastatic malignant melanomas. These were treated with fractionated radiotherapy with various doses per fraction, total doses, and overall times. Cutaneous lesions (127, 53%) were treated with electron beams, and more deeply seated tumors (112, 47%) with 60Co or 4-8 MV X-rays. The fraction size was highly variable, and this permitted determination of the alpha/beta ratio in the multifraction linear-quadratic model, which was estimated at 0.57 Gy with 95% confidence limits [-1.07, 2.5] Gy. Treatment time had no demonstrable influence on TCP. Thus this tumor exhibits the fractionation sensitivity characteristic of a late-responding normal tissue, suggesting that an adequate fractionation schedule for malignant melanomas would be characterized by larger-than-conventional doses per fraction, possibly about 6 Gy per fraction. This is consistent with the conclusions of other authors. Tumor size, evaluated as mean tumor diameter, S, had a major impact on TCP: the number of target cells increased as a power function of S with exponent 0.72 (95% confidence limits [0.49, 0.94]. In fact, a considerable amount of the heterogeneity in the dose response data could be removed by accounting for size. Thus, the weak or absent dose response became highly significant. When a patient had multiple lesions, the responses of these to radiotherapy tended to be similar, thus implying that results were significantly influenced by a "hidden parameter" (such as inherent radiosensitivity or immunological status). A test of the predictive value of the TCP-model was performed in a different series of 183 cutaneous and lymph node malignant melanomas. The observed dose-response relationship in this data set was in good agreement with the model prediction. A chi-square test for goodness-of fit showed that the variation between predicted and observed results could be explained by the binomial variation on quantal response data. PMID- 2587809 TI - Minimizing and measuring lens dose when giving cranial irradiation. AB - Three different techniques of administering cranial irradiation were used to determine the dose to the lens as measured in the Rando phantom. The techniques employed were as follows: (1) the central axis of the radiation beam was placed at the thickest portion of the cranium; (2) the central axis of the radiation beam was placed at the lateral orbital rim (bony canthus); (3) the central axis of the radiation beam was placed at the thickest portion of the cranium but with the beam angled 5 degrees posteriorly away from the eye. Thermal luminescent dosimeters (TLD) were placed in a phantom, at a point determined from a life sized anatomical section of the plane through the midsection of the eye, to be at the location of the posterior capsule of the lens. In addition, TLDs were placed on the outer surface of the phantom head, directly lateral to the location determined to be where the lens would lie. With equally weighted lateral opposed beams, delivering a midplane dose of 200 cGy, the TLDs at the point of the lens measured 21, 9.9 and 10.6% of the midplane doses from the three techniques respectively. TLDs placed directly lateral to the lens on the surface of the phantom head gave an approximation of the lens dose, particularly when techniques 2 and 3 were used. Isodose curve generated by a General Electric treatment planning computer gave lens doses similar to those of the phantom data for each of the three different radiotherapy techniques. Cranial irradiation should be carried out by either technique 2 or technique 3 to minimize radiation dose to the lens. PMID- 2587810 TI - Intensive combined modality therapy of small round cell and undifferentiated sarcomas in children and young adults: local control and patterns of failure. AB - Seventy-five patients (ages 4-35 years) with the following small round cell tumors and undifferentiated sarcoma were treated at the National Cancer Institute: Ewing's sarcoma (n = 32), peripheral neuroepithelioma (n = 14), rhabdomyosarcoma (n = 24), undifferentiated sarcoma (n = 5). Most patients had poor prognostic features including 36 (48%) with metastatic disease, and 42 (56%) with central (truncal) tumors (22 in the pelvis). Treatment included 5 cycles of intensive induction chemotherapy with vincristine, cyclophosphamide and adriamycin, plus aggressive local radiation therapy using simulation and computerized treatment planning for all patients. Thereafter, complete clinical responses were consolidated with intensive chemotherapy, total body irradiation and autologous bone marrow transplantation. There were three local only failures, 10 local plus distant failures, 36 distant only failures, 3 treatment-related deaths, and one intercurrent death. Overall actuarial survival and event-free survival at 4 years are 49 and 29%, respectively. Actuarial freedom from local progression was seen in 74% of patients at 4 years, quite remarkable considering the bulk and location of most of these tumors. Without aggressive surgery, many of these high risk patients had satisfactory outcomes, but better systemic treatments are still needed. PMID- 2587811 TI - Recovery kinetics in mouse skin and CaNT tumours. AB - Recovery kinetics and recovery capacity were studied in a fast proliferating normal tissue, skin, and in an anaplastic mouse mammary carcinoma, CaNT. Three fractions per day of X-rays, repeated over 5 days, were given at varying interfraction intervals from 0 to 8 h. The rate of recovery in tumours (t1/2 = 0.31 +/- 0.15 h for local control) was significantly faster than in skin (t1/2 = 0.96 +/- 0.10 h). By contrast, the fractionation sensitivity of CaNT tumours was less than that of skin (alpha/beta = 43.3 +/- 8.5 Gy vs. alpha/beta = 7.9 +/- 0.2 Gy). Tissues with recovery half-times similar to or longer than that determined for skin would be at risk if interfraction intervals less than 6 h are used in regimes which involve the use of two or more fractions per day. This would be especially true for tissues that show a greater sensitivity to dose fractionation, and hence more sparing of radiation damage with hyperfractionation. PMID- 2587812 TI - Manipulation of oxygenation in a human tumour xenograft with BW12C or hydralazine: effects on responses to radiation and to the bioreductive cytotoxicity of misonidazole or RSU-1069. AB - The influence of altered tumour oxygenation on the responses to radiation and/or bioreductive 2-nitroimidazole compounds was studied in a well differentiated, human, colon adenocarcinoma (MAWI), grown as a subcutaneous xenograft in nude mice. Tumour growth delays were measured after local, single 5-18 Gy doses of X rays. BW12C, which inhibits dissociation of oxyhaemoglobin, produced radioprotection similar to that resulting from clamping off the tumour blood supply during irradiation. Hydralazine, a vasoactive agent, also appeared to give radioprotection. BW12C or misonidazole (MISO) alone had no measurable inhibitory effect on xenograft growth. Hydralazine or RSU-1069 slightly increased the time for tumours to reach 6 times their original volumes. When hydralazine was given 40 min after a dose of 800 mg/kg of MISO, without X-rays, growth delays in excess of 5 tumour volume doubling times resulted and fewer tumour cells were present in histological sections. Lower doses of MISO combined with hydralazine were ineffective. Other combinations of bioreductive cytotoxic agents and methods of manipulation of tumour blood flow/oxygenation induced slight and inconsistent growth delays. Hydralazine was injected after irradiation of tumours in mice previously treated with various doses of MISO in an attempt to exploit the bioreductive cytotoxic potential of MISO in conjunction with its radiosensitizing properties; however, tumour growth delays were similar with or without hydralazine after irradiation. Thus, post-irradiation restriction of tumour blood flow appears to be an ineffective therapeutic strategy in this human xenograft tumour model. PMID- 2587813 TI - Psychiatric prevention and the family life cycle. Risk reduction by frontline practitioners. Group for the Advancement of Psychiatry. PMID- 2587814 TI - [Death on the table during implantation of a hip prosthesis--a neglected peroperative risk?]. PMID- 2587815 TI - [Hemodynamic and respiratory changes in cervical peridural anesthesia]. AB - Regional anesthesia as a method of avoiding stress and preserving the immunological system has found a solid place in the armamentarium of anesthesia departments. Its applicability for anesthesia of higher segments is controversial. In order to test the reliability of this method, at 7 perioperative measuring points we studied respiratory and circulatory parameters of 17 patients undergoing breast surgery. Access to the peridural space was via C6/7 or C7/T1 by catheterization with the hanging-drop method. The respiratory and circulatory parameters were determined by direct measurement of arterial and pulmonary-arterial pressures and by arterial and mixed-venous blood samples. The main criterion was determination of the arterio-venous oxygen difference. It was shown that the cardiovascular and respiratory integrity of the organism remained unaffected. The most marked changes in relation to the starting point were seen at measuring point 5 (40 min after beginning anesthesia): heart rate -22.4% (p less than 0.05), mean arterial pressure -35.1% (p less than 0.05), mean pulmonary arterial pressure + 18.1% (NS), mixed-venous oxygenation -5.5% (NS), arteriovenous oxygen difference +25.9% (NS) arterial pO2 -4.4% (NS) and pCO2 +7.9% (p less than 0.05). --In the hands of an anesthetist fully acquainted with conduction anesthesia, cervical peridural anesthesia for appropriate indications may be proposed as an alternative anesthesiological method. PMID- 2587816 TI - [Complications during implantation of 3260 hip endoprostheses under spinal anesthesia]. AB - There is a tendency to perform increasingly severe operations on patients of advanced age. Because geriatric patients are of greater risk when under anesthesia during operation, it is necessary to be aware of the possible anesthesia-related and operation-related complications. In a retrospective study the complication rate with regard to patients (age, multimorbidity), operation (e.g. number and duration of procedures) and anesthesia was analyzed. Of particular interest were the kind and degree of certain complications at a particular time. Directly following the induction of anesthesia and the second application of cement the complication rate depended on patient age and multimorbidity, but the intraoperative complication rate was closely related to the operation. Sensory spreading of spinal anesthesia was one of the anesthesiological factors leading to an increase in the complication rate. Cardiovascular complications occurred most frequently following the induction of spinal anesthesia (hypotension: 6.50%, tachycardias: 3.74%, bradycardias: 3.68%). The most serious circulatory complication--shock--however was primarily seen during surgery [1.80% (n = 59)]. Asystoles [0.27% (n = 9)] were only seen intraoperatively and after the second cement application. Pulmonary embolism [0.12% (n = 4)], respiratory arrest [0.09% (n = 3)] and exitus [0.64% (n = 21)] exclusively occurred following the second administration of cement. Geriatric patients are particularly at risk directly after induction of anesthesia and following application of the second cement. Thorough preoperative preparation (with regard to the cardiac and circulatory situation), spinal anesthesia of less than Th 6 and a rapid surgical procedure are necessary to reduce the morbidity and mortality. PMID- 2587817 TI - [Comments on the article by P. Hoffmann and A. Franz. Thoracic peridural anesthesia in children]. PMID- 2587818 TI - [Comments on the article by P. Hoffmann and A. Franz. Thoracic peridural anesthesia in children]. PMID- 2587819 TI - [Comments on the article by P. Hoffmann and A. Franz. Thoracic peridural anesthesia in children]. PMID- 2587820 TI - Invasive radiology. AB - The history of invasive radiology is a history of cooperative effort of scientists in physics and chemistry, of engineers in academic settings and industry and of the medical community. Research and development in the technological sciences opened doors to clinical application. Clinical imperatives drove research and development. Parallel advances in catheters, contrast materials and radiologic equipment came together to permit invasive radiologists to pursue advances in diagnosis and therapy, in a setting of patient safety. PMID- 2587821 TI - [Manual dexterity and acquisition of correct dental hygiene]. AB - The aim of this study was to evaluate the relationship of normal dexterity and the ability to obtain correct dental hygiene. Manual dexterity level was determined by means of psychotechnical tests on 35 students. Plaque index was noted before oral hygiene instructions including tooth-brushing and flossing techniques according to BASS. The same index was noted 15 days after instructions. Statistical analysis of results showed no significant relationship between manual dexterity and plaque control efficiency. PMID- 2587822 TI - [Dental prophylaxis by the patient]. AB - Conscientious self-application of oral hygiene procedures by the patient is related to the need to obtain and to keep plaque-free teeth. This need is aroused by pleasant aspects. One appointment is reserved to demonstrated proper plaque control techniques. Instruction on the correct brushing method is explained with the aid of demonstration models and afterwards in the mouth with the use of a hand mirror. It is necessary to confirm the effectiveness of the instructed method in plaque removal with each patient. We describe a modified BASS toothbrushing technique. Patients without periodontitis, for example in case of chronic gingivitis, are instructed for flossing. Patients with periodontitis receive instruction for use of interdental cleaning (floss and/or interproximal brushes). Patient motivation is repeated during treatment period, control routine visit and maintenance phase. At each visit, technique efficiency is controlled visually or by bleeding test and plaque control is corrected. PMID- 2587823 TI - [Surgical and non-surgical approach to deep periodontal pockets]. AB - Deepened pockets are a challenge because they offer an anaerobic niche and because of their inaccessibility to personal plaque control measures. Scaling and root planing followed by regular professional plaque removal are effective in arresting the progress of most chronic adult periodontitis. Only when pockets remain inflamed after repeated thorough professional treatment during several months can a surgical pocket elimination technique be used. The results will depend on the type of attachment loss (horizontal vs. irregular) the root anatomy (furcations) and the training level of the operator, general practitioner or periodontologist. There is an increasing trend in the anterior parts of the oral cavity (monoradicular teeth easily accessible for plaque control) to use the Widman technique. Long-term data concerning the stability of this new attachment are lacking. Gingivectomy is less elaborate, does not imply a high-level sterile environment like for mucoperiosteal flap surgery, but leads to phonetic and esthetic side-effects when used in frontal areas. In the distal areas the apically displaced and the shortened repositioned flap techniques are effective in a long-term perspective if regular postoperative monitoring is respected. Discussion remains concerning the stability of a new connective tissue attachment vs. a long epithelial attachment. A recent breakthrough is the so-called Guided Tissue Regeneration where by means of a submucosally membrane the periodontal ligament cells are allowed to regenerate the different periodontal tissue compartments. Preliminary results are very encouraging but need further evaluation. PMID- 2587824 TI - [The use of antibiotics]. AB - Antibiotic therapy should be oriented towards sensitive pathogenic strains. The problem in most periodontal infections is that the latter are not clearly identified and that culturing techniques to document sensitivity are time consuming (at least 5 days for anaerobes) and cumbersome. Thus for chronic periodontal infections, the choice is based on the clinical diagnosis: juvenile, post-juvenile, chronic adult, periodontitis.... It is known from longitudinal studies that mechanical plaque control can cope with nearly all periodontal infections. Antibiotic therapy should thus be limited to refractory or very aggressive cases, acute complications, immunologically compromised patients and patients with a need for antibiotic coverage during surgical procedures. If needed tetracyclines, metronidazole, clindamycin, bacampicillins are the appropriate adjuvants in different types of infections. Considering the side effects and the increasing resistance of bacterial species, dentists should never use antibiotics without the appropriate local treatment and without a clear-cut indication. Postoperative swelling certainly is not one. PMID- 2587825 TI - Establishing sound blending in moderately mentally retarded children: implications of verbal instruction and pictorial prompting. AB - The present study evaluated a program for establishing blending of consonants (C) and vowel-consonant (VC) syllables in moderately mentally retarded children. The study consisted of two experiments. Experiment 1 assessed whether the subjects' failure to blend was due to the task requirements per se, or to the inadequacy of the instructional terminology ("Say together"). Experiment 2 evaluated the implications of using pictorial prompts in the acquisition and generalization of C-VC blending. The data revealed that (a) adequate verbal instruction had a modest but significant effect on the subjects' blending performance (Experiment 1), and (b) training without pictorial prompts resulted in better blending of trained and untrained C-VC items than training with pictorial prompts (Experiment 2). PMID- 2587826 TI - Establishing conditional discriminations: concurrent versus isolation-intermix instruction. AB - This paper describes an investigation comparing the effectiveness and efficiency (sessions to criterion, errors to criterion, minutes of instructional time) of concurrent and isolation-intermix instruction in teaching four preschool children to read words found in community and school environments. Two students were taught words using constant time delay and two progressive time delay across the two different conditions. Concurrent instruction consisted of two sessions per day where two words were randomly presented within each session until criterion was reached and a conditional discrimination was established. The isolation intermix condition involved two sessions per day where each word was taught in separate daily sessions until criterion was reached and a simple discrimination was established (isolation instruction); followed by random presentation of both words within each daily session until the conditional discrimination was acquired (intermix). Concurrent instruction resulted in students learning conditional discriminations in fewer trials and minutes of instructional time. These data suggest that teachers should structure their instruction to teach conditional discriminations from the beginning rather than teaching simple discriminations. PMID- 2587827 TI - The use of behavior therapy and physical therapy to promote independent ambulation in a preschooler with mental retardation and cerebral palsy. AB - This study investigated the effectiveness of an instructional program designed to promote independent walking in a mentally and physically handicapped pre-schooler involving a collaborative effort between a behavior therapist and a physical therapist in an interdisciplinary setting, a public school. By letting the youngster experience a treatment package culminating in listening to a dishwasher operating for a few minutes contingent on walking increasingly longer distances, he eventually ambulated 150 feet during treatment. Independent walking transferred to nonexperimental settings in the school, home, and community. Follow-up observations at two and 32-month intervals indicated long-lasting treatment effects. Results are discussed in terms of the natural consequences that maintained walking, including response efficiency and social reinforcement, as well as a treatment model that incorporated both the form and the function of the response. PMID- 2587828 TI - A survey of self-restraint, self-injury, and other maladaptive behaviors in an institutionalized retarded population. AB - Psychologists of a state school for mentally retarded persons were surveyed to assess the prevalence of self-restraint, self-injurious behavior (SIB), and other maladaptive behaviors for clients in their facility. Results indicated that almost all clients reliably identified as engaging in self-restraint also engaged in self-injurious behavior while other maladaptive behaviors for self-restraining clients occurred much less frequently. The occurrence of SIB in the school's population was substantially lower than in the self-restraining population. Results are discussed in terms of future research investigating a functional relationship between self-restraint and SIB. Clinical implications for the use of self-restraint as an intervention for SIB also are discussed. PMID- 2587829 TI - Imitation, recall, and imitativeness in children with low intelligence of organic and familial etiology. AB - Groups of noninstitutionalized organic and familial mentally retarded and borderline mentally retarded children at two CA levels were given tasks designed to assess imitation. In contrast to findings from studies of average IQ children, organic low IQ children showed as much imitativeness at the older as at the younger age levels. Consistent with expectations, etiology, independent of IQ, was found to be significant. Familial low IQ children showed more absolute imitation and recall, whereas organic children were more imitative and responsive to the irrelevant behaviors modeled. Findings are discussed in terms of the developmental approach to imitation. PMID- 2587830 TI - Teaching money skills through stimulus class formation, exclusion, and component matching methods: three case studies. AB - This paper describes novel methodology for teaching monetary skills to mentally retarded individuals. The goal of the methodology is to generate such skills with relatively little explicit training. To do so, the procedures were designed to produce emergent new behavior through stimulus class formation, exclusion, and matching of stimulus components. Three case studies demonstrate the methods and provide illustrative supporting data. PMID- 2587831 TI - An individual reference database tool: publish or perish. PMID- 2587832 TI - Does urinary salbutamol reflect compliance with the aerosol regimen in patients with asthma? AB - Compliance with inhaled beta agonist therapy in a group of asthmatic patients in general practice has been monitored using a high performance thin layer chromatographic assay of salbutamol in urine. Urine salbutamol levels were lower than expected in five of 51 patients and much higher than expected in a further 11 patients. These results suggest the assay may be clinically useful for monitoring compliance of asthmatic patients with inhaled salbutamol. PMID- 2587833 TI - Observations on sputum production in patients with variable airflow obstruction; implications for the diagnosis of asthma and chronic bronchitis. AB - There are few clinical studies on hypersecretion in asthma, defined as variable airflow obstruction. One hundred and thirty defined asthmatics were questioned in detail about their clinical features, with special reference to sputum production. Other clinical and laboratory data were obtained from the hospital notes. Thirty (23%) denied sputum production at any time. Of the hundred patients reporting sputum, 55 reported the largest volume when an attack of asthma was at its worst and 42 reported most sputum during recovery. Three patients reported unchanging sputum volumes regardless of asthma attacks. There was an association between greater sputum volumes and increased absenteeism due to respiratory symptoms (P less than 0.01) and negative prick skin tests (P less than 0.001). Cigarette smoking and bronchopulmonary aspergillosis were uncommon among our patients, and did not alone account for the sputum production rates. Sixty-eight per cent of patients reported that their pattern or volume of sputum production during attacks had not changed substantially since the onset of their asthma. Patients also fulfilling the Medical Research Council (MRC) criteria for chronic bronchitis (n = 56) were more likely to have smoked than those who did not (P less than 0.005), although 32 (57%) of the asthmatics with chronic bronchitis had smoked little or not at all. Moreover the lability of peak flow measurements was similar in asthmatic patients with and without chronic bronchitis (Lability index 43 and 42% respectively). The prevalence of persistent airflow limitation (PAL) in addition to a variable component related to duration of asthma but not to smoking. The relation between PAL and sputum production was complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2587834 TI - Respiratory medicine research in the 1990s--the next ten years. PMID- 2587836 TI - An audit of morbidity associated with chronic asthma in general practice. AB - A survey of 312 adult asthmatic subjects has been undertaken. Only 3.5% of the total adult list were known to have asthma and this may represent underdiagnosis. Spirometry was normal in under half the patients and below 50% predicted in one fifth. Forced expired volume in 1s had declined more rapidly than expected with increasing age, particularly amongst smokers. Morbidity from asthma was extensive, patients reporting substantial breathlessness and restrictions of their life style; nearly half had lost time from work in the preceding twelve months. Morbidity was correlated with spirometry. PMID- 2587835 TI - The value of ear lobe oximetry in the assessment of disability in asbestos related disease. AB - Thirty-four asbestos workers, with either asbestosis, diffuse pleural thickening, calcified pleural plaques, or with comparable asbestos exposure but no evidence of asbestos-related disease and seven normal controls underwent a progressive exercise test. The subjects were categorized on the basis of lung function tests and PA chest X-rays. During the exercise test oxygen saturation was measured continuously by an ear lobe oximeter. The asbestosis and diffuse pleural thickening groups showed significant oxygen desaturation on exertion, confirming that both these conditions give rise to appreciable respiratory disability. PMID- 2587837 TI - Positive Kveim reaction in eosinophilic pneumonia. AB - The Kveim test is generally regarded as highly specific for sarcoidosis. We report two patients with pulmonary eosinophilia who had positive Kveim reactions. This association has not been previously reported. PMID- 2587838 TI - Long-term effects of phenobarbital on rat liver microsomal drug-metabolizing enzymes and heme-metabolizing enzyme. AB - Long-term effects of phenobarbital on changes of rat hepatic enzymes involved in drug and heme metabolism were examined by employing two different treatment schedules which produce tolerance (tolerant group) and/or dependence (dependent group) against the drug. In both treatment groups, phenobarbital produced a marked and persistent induction of cytochrome P-450 and aminopyrine N demethylase; the response was greater in the tolerant group than that in the dependent group at the early time periods. Thereafter, the magnitude of the induction of drug-metabolizing enzymes gradually decreased and finally was maintained at two-fold of the corresponding control levels. Likewise, the induction of cytochrome P-450b+e content, one of the major phenobarbital inducible species, was maintained at 40% of the total cytochrome P-450 content. Phenobarbital treatment resulted in increase of delta-aminolevulinate synthetase (ALAS) activity and a decrease in heme oxygenase (HO) activity. Changes of these enzymes involved in heme metabolism coincided with changes of the drug metabolizing enzymes. Finally, the changes of enzyme content and activity after terminating phenobarbital treatment were determined and enzyme biological half lives were calculated employing protein synthesis inhibitors. No significant differences in the changes of cytochrome P-450 and cytochrome P-450b+e content between the groups were observed after terminating phenobarbital treatment. However, changes of ALAS and HO activities after terminating the drug were significantly different between the groups; changes in the dependent group corresponded to the decrease in serum phenobarbital levels. On the other hand, biological half-lives of microsomal drug-metabolizing enzymes were longer in the tolerant group than in the dependent group. PMID- 2587839 TI - Changes in lymphocyte function and lung histology during the development of asbestosis and silicosis in the mouse. AB - In order to study changes in lung histology and lymphocyte function during the development of pneumoconiosis, three groups of Balb/c mice were intratracheally instilled with either saline, chrysotile asbestos or silica particles and then sacrificed at different times. Asbestos-instilled mice showed collagen deposits at 2 months while silica-instilled mice showed severe fibrosis at that time. Stimulation of splenic cells with LPS was not affected by instillation of the toxic particles. Stimulation with PHA and ConA, however, induced increased responses especially at 3 and 6 months after instillation of asbestos or silica. A diminution of mitogen-induced proliferation was observed in aged mice. There was no correlation between changes in splenic cell proliferation and development of fibrosis. Asbestos fibers added in vitro, inhibited PHA and ConA-induced proliferation, partially due to prostaglandin (PG) production and to the presence of the fibers during the assay. When asbestos fibers were removed by washing, no inhibition was observed. Moreover, actual stimulation of proliferation was noted when PG production was inhibited in vitro with indomethacin. In contrast, in vivo treatment of asbestos-instilled mice with indomethacin had no effect on the development of lung pathology. PMID- 2587840 TI - Synthesis and biological activity of a new squaric acid-formylmethionine peptide conjugate. AB - A new squaric acid-formylmethionine peptide has been synthesized. In view of its biological properties to induce lysosome release and to inhibit glyoxalase, this compound may be of pharmacologic value. PMID- 2587841 TI - Clinical features and diagnosis by recombinant DNA techniques of familial amyloid polyneuropathy in Japan. AB - Diagnosis of familial amyloid polyneuropathy (FAP) was investigated by recombinant DNA techniques using Southern blot hybridization in 49 constituents of FAP pedigrees originated from Nagano and Hiroshima Prefectures in Japan. The results were correlated with clinical features of the patients. Twenty-nine patients originated from Ogawa Village in Nagano Prefecture of the central part of Japan had typical clinical features of Andrade type FAP including polyneuropathy with autonomic disorders. The variant prealbumin gene with a substitution of methionine (Met) for valine (Val) at position 30 was detected in their DNA analysis (positive DNA diagnosis). In 5 cases from Nagano and Hiroshima Prefectures who had clinical features of Andrade type FAP but no family history, DNA diagnosis was positive. In another 5 members of FAP pedigrees originated from Ogawa Village without clinical features of FAP, DNA diagnosis was positive. Two cases originated from Iiyama City in Nagano, who had central nervous system disorders resembling spinocerebellar degeneration with spastic paraplegia besides clinical features of Andrade type FAP, had the Val-Met interchange variant prealbumin gene. In a case from the same Iiyama family who had only the central nervous system disorders without clinical features of FAP, DNA diagnosis was negative. These findings indicate that the presence of the variant prealbumin gene closely linked to the clinical manifestations of Andrade type FAP. The diagnostic DNA analysis was considered to be useful for the diagnosis of Andrade type FAP for sporadic cases as well as so far nonsymptomatic gene carriers. In conclusion, FAP patients originated from Iiyama City and Ogawa village were considered to have the same mutation despite the variances in clinical features. PMID- 2587842 TI - Inhibition of paraquat accumulation in rabbit kidney cortex slices by ascorbic acid. AB - Effects of ascorbic acid and Fe2+ on the accumulation of paraquat into rabbit kidney cortical slices were studied. Ascorbic acid showed dose-dependent inhibition of paraquat accumulation. Fe2+ had a more powerful stimulatory effect on the lipid peroxidation of cortical slices than ascorbic acid, but it did not reduce paraquat accumulation. These results suggest that ascorbic acid is able to inhibit the accumulation of paraquat independent of its peroxidative action, and that ascorbic acid may serve as an antidote for the toxicity of paraquat. PMID- 2587843 TI - Evaluation of nickel complexes of bioligands-effect on distribution profile. AB - Distribution of various nickel-63 bioligand complexes in tissues of rats and their binding to subcellular fractions have been studied. Nickel-binding with glutathione and histidine significantly decreased nickel-63 accumulation while nickel-serum binding increased nickel body burden and its accumulation is subcellular fractions. Nickel-renal cytosol binding exhibited distribution pattern similar to serum complex only in lung tissue. PMID- 2587844 TI - Adrenocortical response to stress in rats exposed to lead nitrate. PMID- 2587845 TI - Sex-related alteration of drug action in carrageenan-induced inflammation in the rat. AB - Twenty-four hours after treatment with carrageenan the duration of hexobarbital induced hypnosis was prolonged in males but not females in Wistar rats bearing carrageenan-induced paw edema. Similar treatment with carrageenan led to significant inhibition of the metabolism of hexobarbital by hepatic enzymes obtained from male but not female animals. These data suggest that there is a sex related difference in the ability of carrageenan to alter drug actions in rats. PMID- 2587846 TI - Modification of cyclophosphamide-induced urotoxicity by buthionine sulfoximine and disulfiram in mice. AB - The effect of buthionine sulfoximine (BSO) and disulfiram (DSF) on the urotoxicity induced by cyclophosphamide (CPA) was examined in mice. Pretreatment of mice with BSO (500 mg/kg, i.p.) 5 hr prior to CPA resulted in enhanced urotoxicity of CPA. In contrast, simultaneous administration of DSF (200 mg/kg, p.o.) decreased the urotoxicity of CPA. PMID- 2587848 TI - Comparison of biological and physical properties of human and animal A(H1N1) influenza viruses. AB - The study of biological properties of influenza virus strains belonging to the same subtype A(H1N1) and closely antigenically related, but isolated from different animal species (man, pig and duck), demonstrated that avian strains were more resistant than those isolated from mammals to high temperature and low pH, as shown by titration of residual infectivity in cell cultures (MDCK) and by sialidase assay. The difference in behaviour could be correlated to biological adaptation of the virus to its host. Avian body temperature is 40 degrees C and influenza virus, in ducks, is enterotropic and therefore capable of passing through the low pH values in the upper digestive tract of the animal. These results do not contradict the hypothesis of a possible filiation between avian and mammalian orthomyxoviruses. PMID- 2587847 TI - Hypotriglyceridemic action of omega-3 fatty acids in healthy subjects does not occur by enhanced lipoprotein lipase and hepatic lipase activities. AB - Single blind administration of EPA-rich omega-3 fatty acids at 3 dose levels of 3g, 6g and 12g/d (each dose lasting 3 weeks was separated by 2 weeks on placebo) lowered plasma TG levels and lecithin cholesterol acyltransferase-molar esterification rate (LCAT-MER) activity (6.12g/d). Lipolytic enzymes activity (LPL and HL) remained unchanged at these doses. Fat malabsorption was unlikely because of unmodified plasma beta-carotene, retinol and alpha-tocopherol levels. PMID- 2587850 TI - 2nd forum in virology. Vaccinia-vectored vaccines--risks and benefits. PMID- 2587851 TI - The promise and challenge of vaccinia-vectored vaccines. PMID- 2587849 TI - Use of in vivo challenge to assess rubella immunity determined by haemagglutination inhibition and latex agglutination. AB - In order to estimate the protection afforded by low levels of rubella antibody, pregnant women were tested by haemagglutination inhibition (HAI) and latex agglutination (LA). Fifty-nine women whose sera were HAI-negative (less than 25 IU/ml) or weakly positive (25 IU/ml) received rubella vaccine (RA 27/3) after delivery. Serum samples were collected one week and one month after immunization and tested for rubella total antibody and rubella IgM and IgA antibody. No patients found positive by HAI and LA showed any evidence of primary immunization. Furthermore, rubella IgM antibody was never detected after immunization in women who were HAI-negative and LA-positive during pregnancy. These results show that low antibody titres detected by LA are sufficient to protect individuals against infection with the attenuated virus. It is conceivable that such low titres also ensure protection against natural rubella infection. PMID- 2587853 TI - Vaccinia-vectored vaccines for exotic disease immunization programmes. PMID- 2587852 TI - How do vaccinia-vectored vaccines fit into human immunization programmes? PMID- 2587854 TI - Live poxvirus-vectored vaccines in wildlife immunization programmes: the rabies paradigm. PMID- 2587855 TI - How do other poxviruses fit in as potential vectored vaccine substrates for animal immunizations? PMID- 2587856 TI - Information needs and information seeking behaviour in primary health care. AB - A questionnaire survey of 186 general practitioners in Sweden showed that 67% saw the overall supply of medical information as less satisfactory or unsatisfactory, and that 80% experienced major hindrances in seeking relevant information. The most frequent need for information concerned general medicine, with respect to both diagnosis and choice of therapy. Of situations which required additional information, only every second was completely resolved. These results imply a need for a reorganization of the supply of information to general practitioners. As they cannot depend on conventional medical libraries for day-to-day information, personal libraries should be improved and updated regularly, and be readily to hand. Computer technology should be considered for communication between health care providers, and as support for differential diagnosis in general medicine. PMID- 2587857 TI - Incidence of sickness certification. Proposal for use as a health status indicator. AB - Cause-, sex-, and age-specific incidences of sickness certification in a total population are reported. The population at risk of having a sickness certificate issued was 106,019 employed persons 16-69 years of age. The annual incidence of sickness certification was estimated at 580 per 1,000 employed persons per year (females 596, males 568). The most frequent causes of sickness certification, according to diagnostic groups, were diseases of the respiratory system, musculoskeletal/connective tissue diseases, mental disorders, and injuries. Adjusted for age, injuries were found to be less frequent causes of sickness certification among females than males (p less than 0.001), while the reverse was true for mental disorders (p less than 0.01). Among single diagnoses, "other nonarticular rheumatism" (including myalgia) was more frequent among females than males, while the opposite was true for "backpain without radiating symptoms" (p less than 0.001). Comparisons with morbidity studies indicate that diagnoses stated on initial certificates, issued to employed persons in the total population, give a reflection of a population's health problems. This suggests that sickness certification may provide a basis for a health status indicator which may prove useful in planning and evaluation of occupational health, general practice, and community health. PMID- 2587858 TI - Training specialists in community medicine in Norway. AB - In Norway there is a century-long tradition for letting "the combination-doctor" work with both individual curative treatment and preventive health work in the community. A training programme for the medical specialty "community medicine" has been developed, and it requires at least five years of postgraduate training: one year in general practice, one year in a clinical hospital department, three years of guided community medicine in a municipality, four months of theoretical education within epidemiology, biostatistics, environmental medicine, social medicine, planning, economy, and management. Approximately 50% of the 448 municipalities in Norway now employ a specialist in community medicine. The goal is more than one specialist in every municipality. PMID- 2587859 TI - Uricult and Sensicult dipslides for diagnosis of bacteriuria and prediction of drug resistance in primary health care. AB - Uricult dipslide as an indicator of bacteriuria yielded acceptable results in primary health care (PHC), and readings by local staffs were similar to those by laboratory technicians. Sensicult dipslide detected somewhat fewer bacteriurias and predicted bacterial drug sensitivity better than resistance (predictive values 93% and 50%, respectively). The mean risk of bacterial drug resistance against seven common urinary tract infection (UTI) antibiotics in PHC was 17%. The use of Sensicult for targeting UTI therapy resulted in an average risk of 7% for prescribing drugs to which the organism was resistant. The corresponding risk with Uricult for classification of UTI bacteria by Gram grouping, lactose and catalase reactions, and local guidelines for therapy of different bacterial groups, was also 7%. The latter method is simple, offers qualitative, and thus prognostic information, but can be further improved. PMID- 2587860 TI - Psychotropic drugs--in north and south, east and west. PMID- 2587861 TI - Can regional differences in consumption of tranquillizers and hypnotics be explained by variations in general practitioners' threshold of prescribing? A methodological study. AB - Large differences exist in the consumption of tranquillizers and hypnotics within and between countries. The present study investigates the hypothesis that regional differences in the utilization of tranquillizers and hypnotics are associated with corresponding differences in thresholds of prescribing. A questionnaire that described in a standardized manner 12 patients with a symptomatology of anxiety and insomnia was sent to all general practitioners in two regions (south/north) in Norway. In the south, tranquillizers and hypnotics are used much more frequently than in the north. Based on written simulations of patients, no differences in thresholds of prescribing was found between the general practitioners in the two regions. Neither could the doctors' choice of drugs, nor their recommendations for dosage and duration of treatment, explain the different consumption of tranquillizers and hypnotics in the two regions. The method could, however, be criticized for insufficient validity, since our case stories were less controversial with respect to psychotropic drug prescribing than intended. PMID- 2587862 TI - Perceived and presented morbidity in general practice. A study with diaries in four general practices in The Netherlands. AB - In four general practices in The Netherlands, 277 respondents reported in a diary on perceived morbidity during four weeks. Data of presented morbidity were provided by the general practitioners in these practices, who were accustomed to morbidity registration. As a mean, one complaint was reported every three or four days. Most complaints concerned disorders of the musculo-skeletal system, psychological disorders, and disorders of the upper respiratory tract and the digestive tract. About one-third of all complaints led to medicine taking. According to the GPs' records, one in five of the respondents consulted their GP. Approximately 10% of the complaints were reported to the GP. There was a connection between family members with respect to the frequency of reporting complaints. Because of selection of participating practices, families and respondents, the result can not be applied to the Dutch population as a whole. The results of this study agree with most of the literature on this subject. PMID- 2587864 TI - Quantification of pyuria by two methods correlation and interobserver agreement. AB - The aim of this study was to correlate the results of two methods of quantifying pyuria and to compare the diagnostic reliability of the two methods in terms of interobserver agreement. Three independent observers counted leucocytes in 56 urine samples by using high-power-field (HPF) microscopy on centrifuged urine sediment and by using a Burker haemocytometer on uncentrifuged urine. The commonly accepted diagnostic level of ten leucocytes/mm3 in the haemocytometer was found to be equivalent to two leucocytes/HPF. This agrees with other reports but contrasts with the usual notion of a diagnostic level of five to ten leucocytes/HPF, and implies that urinary tract infection in the presence of symptoms should not be ruled out when less than five leucocytes/HPF are found. Kappa statistics were used to evaluate the interobserver agreement. The observers agreed on the diagnosis in 96% (K = 0.92) of the urines when the haemocytometer was used, and in 93-96% (K = 0.81-K = 0.91) when leucocytes were counted per HPF. The differences in Kappa values were not statistically significant. Our material indicates that the method of quantifying pyuria in centrifuged urine sediment by HPF microscopy may be used as the routine method in general practice. PMID- 2587863 TI - The "true" prevalence of obesity. A comparison of objective weight and height measures versus self-reported and calibrated data. AB - A regression model that describes the relationship between body mass index (BMI, kg/m2) based on self-reported weight and height, and body mass index based on objective measurements, makes it possible to calibrate the BMI based on self reports. Calibrated data on prevalence of obesity are much higher than those calculated from self-reports. The aim of the present study was to evaluate which estimates of prevalence of obesity agreed better with objective values, those based on self-reported data or those based on calibrated BMIs. Results from two different representative samples of the same Swedish rural county were compared. Objective values were based on measurements of 2190 men and 1511 women (25-65 years of age) in 1977. Self-reports from 148 men and 147 women (25-64 years of age) were derived from the ULF-study, 1980-81 (Survey on Living Conditions) and then calibrated. The comparison demonstrated that calibrated data, compared with self-reports, are much closer to objective values. There was a striking agreement between objective (14.0%) and calibrated (13.6%) estimates of prevalence of women with BMI greater than 30.0 kg/m2, in contrast to the under-estimation by self reports (8.1%). The calibration method was reliable for the evaluation of the "true" prevalence of obesity in population studies. PMID- 2587865 TI - The relationship between serum enzyme activity, infarct site, and cardiac complications after a first myocardial infarction. A follow-up study in general practice. AB - The aim of the present study was to relate the clinical course in patients after a first acute myocardial infarction with the site and size of infarct, estimated from standard enzyme measurements. One hundred and eight consecutive patients who suffered an acute myocardial infarction for the first time were followed-up after 30 months in general practice. Twenty-six patients had died and 8 had had another infarction. Sixty-two of the surviving patients had received treatment for ischaemic heart disease, usually for angina pectoris and less often for heart failure and arrhythmias. No correlation was found between ischaemic heart disease requiring treatment and the enzyme-estimated size or the site of the infarct. With anterior infarcts there was, however, an overweight of arrhythmias requiring treatment. Of the patients at work, 31% had changed job or job status because of ischaemic heart disease. At the end of the 30 month period, 50 patients were in functional class 1 and 2, and 32 in functional class 3 and 4 (New York Heart Association's classification). PMID- 2587866 TI - The Reason-for-Encounter mode of the ICPC: reliable, adequate, and feasible. AB - For three consecutive months, eight general practitioners reported and classified all reasons for encounter presented by their patients. They were taking part in an international trial of the WHO-ICPC Committee, utilizing a trial version of the 'Reasons-for-Encounter' (RFE-C)1. This scale has now been integrated with the newly developed 'International Classification of Primary Care' (ICPC)2. Attention was given to reliability, adequacy, and feasibility. Results indicated that the trial version of this classification system is highly reliable; the participating doctors found it both adequate for their purposes and feasible for use in their practices. PMID- 2587867 TI - Multicentre trials in general practice. PMID- 2587868 TI - Treatment of patients with airflow obstruction by general practitioners and chest physicians. AB - The study comprised 223 patients with airflow obstruction and/or bronchial hyperreactivity from 29 general practices in the catchment area of Nijmegen University. Fifty-six patients were treated by 19 chest physicians, the remaining 167 by their general practitioners (GPs), without specialist care. The specialists treated more allergic patients than the GP (p less than 0.05). No other relevant differences in sex, age, smoking behaviour, and severity of the disease (symptoms, lung function, and bronchial hyperreactivity) could be observed between these two groups of patients. Chest physicians prescribed almost three times as many drugs as GPs. No immediate response to the prescribed bronchodilators was found in 16% of the patients treated by the GPs, nor in 20% of the patients treated by the specialists. We could identify only a weak relationship between the severity of the disease (symptoms and pulmonary function combined) and the prescribed pharmacotherapy: with growing degrees of severity the GP seems to prescribe more bronchodilators, the specialist more inhaled corticosteroids. Prescribed pharmacotherapy should be based on the combination of symptoms, pulmonary function, bronchial hyperreactivity, and reversibility on the prescribed bronchodilators. PMID- 2587869 TI - Health centre efficiency. First results of an organizational analysis of four Finnish health centres. AB - First results are given on the opinions and perceptions of the health centre personnel (including administrative staff, doctors, nursing and office personnel) concerning their work at four health centres, which represent different types of organization with respect to urbanrural axis, geographical location, and size of base population. Data were collected using a pretested questionnaire. The number of completed forms was 710, of which 702 were included in the final analysis. The response rate was 95%. The results indicated that doctors and administrative staff considered their work mentally more stressful than the other groups. According to the doctors, important adverse factors in their work were 1) the forced pace of work and 2) the perceived haste and tight schedule. The findings also suggest that, at least in those health centres studied, communication between various professional groups was insufficient. Likewise, the transfer of information between the various functional units was problematic. These findings may indicate difficulties in the planning, organization, and coordination of the work. Therefore the attention should be focused especially on the management of health centre organizations. PMID- 2587870 TI - Heavy users of prescription drugs--mortality and stability in use patterns. AB - Longitudinal analyses of heavy users of prescription drugs were carried out in a geographically defined population in mideastern Sweden. During the period 1976 1983 the individual stability in heavy use of prescription drugs was analysed in heavy users identified in 1975. Mortality of heavy and nonheavy users during the same period was also studied. The 10% with the heaviest use accounted for more than 40% of total drugs prescribed. A substantial proportion of heavy users continued heavy use for eight or more years. These continuing heavy users accounted for more than 7% of total drugs prescribed during 1983. Individual stability in heavy use of prescription drugs over time varied with age. Continued heavy use was not common in the youngest heavy users, whereas a substantial proportion of older heavy users continued with such use over time. There were no differences between men and women in continued heavy use. Heavy users with use of hormonal drugs, including anti-diabetics, or use of psychotropics had a greater tendency towards continued heavy use, compared with heavy users without such use. Heavy users with use of antibiotics, systemic drugs for allergies or drugs for ear, nose, and throat conditions had a lower tendency towards continued heavy use over time, compared with other heavy users. Heavy users of prescription drugs had a higher mortality, compared with nonheavy users. PMID- 2587872 TI - Metabolic evaluation of non-insulin-dependent diabetes in primary health care- the clinical usefulness of glycated haemoglobin measurements. AB - To evaluate the clinical usefulness of measurements of glycated haemoglobin in the assessment of metabolic regulation in non-insulin-dependent diabetes mellitus (NIDDM) in primary health care, measurements of glycated haemoglobin, HbA1c, were compared with postprandial blood glucose measurements. 120 consecutive patients with NIDDM, following the routine control by their general practitioners, were offered a measurement of HbA1c. Approximately two-thirds of the patients had HbA1c values above the acceptable level, despite postprandial blood glucose values within the recommended intervals of good and acceptable metabolic control. Blood glucose values above 10.0 mmol/l, indicating poor metabolic regulation, were reflected in high HbA1c values. Measurements of HbA1c provide an index of metabolic regulation over time, which is otherwise not obtainable in the usual clinical setting, and HbA1c should be measured regularly to evaluate long-term metabolic control and the need for intensified therapy in patients with NIDDM. PMID- 2587871 TI - Prevalence of hepatitis B virus markers in a random sample of women from Goteborg, Sweden. AB - The prevalence of the hepatitis B markers HBsAg, anti-HBc and anti-HBs was studied in 540 women from a randomised sample of women representative of the total population of women in Goteborg, Sweden at the ages of 26, 38 and 50 years. The prevalence of hepatitis B markers was 5.9%. No significant differences were found between the women with hepatitis B markers and the total population concerning education, place of residence during childhood, history of admission to hospital, surgery or blood transfusion, abuse of drugs or alcohol, life-time number of sexual partners or liver function tests. Only 8 of 37 (22%) women with hepatitis B markers had a history of jaundice. We conclude that psychological factors had no strong influence on the prevalence of hepatitis B in Swedish women in general. PMID- 2587873 TI - Group-based training for general practice in Norway: making a new model work. AB - In operation since 1985, the Norwegian five-year postgraduate educational programme for general practitioners is based on one year's hospital training and four years of training in general practice. One of its main components is a two year group-based educational programme. Since there was little previous experience to rely on when setting these groups to work, there has been some concern as to whether the system would work--and how. This paper summarizes the practical experience of the first 45 groups established, based on a questionnaire filled in by the group leaders during their third one-week trainer course. There had been few problems that were not solved by the groups themselves. All 45 groups, including 326 participants, fulfilled the 40 scheduled three-hour meetings within two and a half years. This group-based educational system is now an alternative to the traditional one-to-one trainer/trainee relationship established in many countries as a part of the postgraduate training for general practitioners. PMID- 2587874 TI - Patient compliance in general practice. AB - The article is a short summary of a PhD-thesis, which was accepted by the Faculty of Medicine, University of Copenhagen, May 1989. The thesis is written in Danish with an English summary. It can be obtained free at the Department of General Practice, University of Copenhagen, Juliane Maries Vej 18, DK-2100 Kobenhavn O, Denmark, as long as issues are still available. PMID- 2587875 TI - Self care, social support and health. Theoretical analysis and population study in four villages in Eastern Finland. PMID- 2587876 TI - Digitalis in general practice. PMID- 2587877 TI - [What is your diagnosis?]. PMID- 2587878 TI - [What is your diagnosis?]. PMID- 2587879 TI - [The university and general medicine]. PMID- 2587881 TI - [Percutaneous occlusion therapy of idiopathic varicocele as an alternative to operation]. AB - Percutaneous sclerotherapy of varicocele is performed at the Kantonsspital of St. Gallen since 1983 as an alternative to the conventional operation. The main indication to treat varicocele was an associated fertility disorder. Success rate was around 60%. Adverse reactions of the treatment occurred in only 6.5%. The procedure can be done on an outpatient basis, is well tolerated by patients, economic and is associated with only minimal complications. PMID- 2587880 TI - [The treatment of essential hypertension in the hospital and in the office: is there a difference?]. AB - An identical antihypertensive regimen with Metoprolol, a beta-blocking agent, was compared in two groups of patients with mild to moderate hypertension regarding effectiveness and side effects. 17 patients were treated by practitioners, 28 patients at the university clinic. The aim of the comparison was to appreciate possible effects of the clinical setting. With respect to the blood pressure reduction no difference was found between the two groups. Significant differences were noted however regarding side-effects. The practitioners reported fewer and less serious side-effects. This observation should caution about similar phenomena in similar studies and lead to modification of planning in future studies. PMID- 2587882 TI - [Visual perception and its disorders]. AB - It's the brain and not the eye that decides what is perceived. In spite of this fact, quite a lot is known about the functioning of the eye and the first sections of the optic tract, but little about the actual process of perception. Examination of visual perception and its malfunctions relies therefore on certain hypotheses. Proceeding from the model of functional brain systems, variant functional domains of visual perception can be distinguished. Among the more important of these domains are: digit span, visual discrimination and figure ground discrimination. Evaluation of these functional domains allows us to understand those children with disorders of visual perception better and to develop more effective treatment methods. PMID- 2587883 TI - [Non-healing foot wound]. AB - A young man from Sri Lanka developed a suppurative chronic wound on the right foot after a minor trauma. In spite of several surgical interventions a closure of the ulcer did not occur. Only six months later after serious miliary tuberculosis had developed the correct diagnosis was established and tuberculostatic therapy initiated. This manifestation of tuberculosis--rare in recent times--is reviewed. Emphasis is placed on the causal relation between trauma and reactivation of tuberculosis as well as the pathogenesis of secondary miliary tuberculosis. PMID- 2587885 TI - [A case from practice (154). 1. Renovascular hypertension. 2. Type II diabetes mellitus. 3. Grade II/b peripheral arterial occlusive disease]. PMID- 2587886 TI - [What is your diagnosis? Thioridazine poisoning]. PMID- 2587884 TI - [Osteoporosis: a case report]. AB - A 56-year-old female patient was admitted to our hospital because she was suffering from severe osteoporosis. The patient had experienced repeated spontaneous fractures for 1.5 years such as serial rib fractures, fractures of the sternum and most recently fracture of the neck of the femur after a minimal trauma. Histology revealed a low-turnover-osteoporosis. Subsequent radiologic examination showed extreme osteoporosis of the skeleton with numerous compression fractures of the vertebral bodies as the most outstanding finding. The bone histology and the relatively short history of spontaneous fractures led us to investigate endogenous hypercortisolism as a possible cause although clinical signs were absent. An attenuated diurnal variation of cortisol levels and lack of suppressibility of cortisol was found. Furthermore, magnetic resonance tomography showed a microadenoma of the pituitary gland. Computerized tomography of the adrenals was normal. Transsphenoidal surgery confirmed the tentative diagnosis and histological examination revealed a bilateral adenoma of the pituitary gland. PMID- 2587887 TI - [Distribution and acceptance of self measurement of blood pressure in the Hamburg area]. AB - According to a pilot study in the Hamburg area 17% of the hypertensives practised home measurement of blood pressure. 2/3 of the remaining 83% were informed about the method, but not sufficiently. Half of the patients on home recording bought the device of their own accord. They were not trained by qualified personnel and their technique was not reviewed. Nearly 2/3 of the patients on home recording were mildly hypertensive. 3/4 of those with severe hypertension received a prescription for the device from their doctors. 3/5 controlled their blood pressure daily, 3/4 additionally if necessary. Those registering elevated values reacted on the whole reasonably. Dosages could be reduced in 1/4 of the cases, 2/5 of the patients consulted their doctors less, more than half came to a positive attitude towards their disease. There were mostly good reasons for buying a home device. 90% of the hypertensives accepted the method of self measurement. Only 10% were unable to practise home recording and felt a certain uneasiness. PMID- 2587889 TI - [Self measurement of blood pressure: patient education]. AB - Many patients measure their blood pressure without any instruction due to the availability of modern measuring devices. Although the technique can be mastered by most of the patients, some sources of error have to be eliminated. The aim of such an instruction is to explain these sources of error to the patients and to give them opportunity to practise the self measurement under medical supervision. An instruction sheet is handed out as a pamphlet. The patients are also directed to keep a record of all measurements which is periodically controlled by the physician. It is also advisable to reexamine the measuring technique of the patient from time to time and to check the accuracy of the patients measuring device. PMID- 2587888 TI - [ Self measurement of blood pressure. Equipment and comparison of equipment]. AB - Precision is the primordial criterion for the evaluation of a blood pressure measuring device. While traditionally devices based on the auscultation technique have dominated semiautomatic devices have recently gained acceptance. The latter permit to reduce procedure-related errors. They are simpler to use and require less demanding instruction but are more expensive than stethoscopic devices. PMID- 2587890 TI - [Why are blood pressure values higher in the doctor's office than at home?]. AB - Blood pressure values measured by the patients at home are lower than those measured during medical consultation. To test whether the person measuring the blood pressure is responsible for this difference, the blood pressure of 127 patients was measured first by the doctor and then by the patients themselves during the consultation. There was a good agreement and no significant difference between the two measurements. Values taken at home were however significantly lower. Our results indicate, that difference between clinic and home blood pressure values does not depend on the person performing the measurement. PMID- 2587891 TI - [The time bomb AIDS and epidemiology legislation]. PMID- 2587892 TI - [Pneumocystis carinii pneumonia in AIDS patients. Aspects of clinical evolution in 37 cases]. AB - This study concerns 37 cases of Pneumocystis carinii pneumonia in AIDS patients. The time elapsed between human immunodeficiency virus (HIV) seropositivity and the onset of pneumocystosis has been established. Three clinical types are individualized. In cases with normal X-ray films of the chest, measurement of carbon dioxide transfer capacity, always reduced, has led to a bronchoalveolar lavage which provided an early diagnosis. In spite of good response to treatment, the prognosis of pneumocystosis is poor owing to the frequency of associated diseases. PMID- 2587893 TI - [Eosinophilic pleural effusion]. AB - Eosinophilic pleural effusion accounts for 5 to 10% of all clear liquid pleurisies. Its pathogenic significance is unclear and its relation to the causative diagnosis of pleural eosinophilia is diversely evaluated. In this study, 86 cases of eosinophilic pleural effusion observed at the Ariana Pneumophthisiology Hospital over a 5-year period are reviewed. At first aspiration, the proportion of pleural fluid eosinophils varied from 12% to 85% (54% on average). Blood eosinophilia was present in 60% of the patients. The main cause of effusion was tuberculosis (39.6%, but many other diseases were observed; despite numerous investigations, no cause could be found in 23.2% of the cases. The discovery of a pleural eosinophilia has an impact on the probable cause of the pleurisy, and this can be determined by applying Bayes' rule. The probability of tuberculous being the cause falls from 70.3% for clear liquid pleurisies generally to 44.6% for eosinophilic pleurisy. The probability of cancer as a cause falls from 4.5% to 0.66%; whereas that of "idiopathic" pleurisy rises from 13.5% to 59.56%. These findings are concordant with Adelman's conclusions. In other words, the finding of a pleural eosinophilia decreases the probability of tuberculous or malignant pleural effusion and increases the probability of benign or "idiopathic" effusion. Clinicians confronted with an eosinophilic pleural effusion should be particularly careful and accurate since this diagnosis may spare the patient an unnecessary exploratory thoracotomy and an unwarranted antituberculous treatment. PMID- 2587894 TI - [Radiological case report. Recurrent pneumothorax in a 74 year old patient]. PMID- 2587895 TI - [A new case of necrotizing pneumocystosis in AIDS]. AB - The authors report the case of an AIDS patient presenting with both Streptococcus pneumoniae pneumoniae and pneumocystosis. What was remarkable in that case was the appearance, in an otherwise favourable course, of a large excavation in the territory of the pneumonia. The responsibility of Pneumocystis carinii in this excavation is discussed. PMID- 2587896 TI - [Bronchial infection and brain abscess caused by Pasteurella multocida]. AB - The authors report a case of pasteurellosis with abscess of the brain consecutive to a bronchopulmonary infection in a woman with old-standing bilateral bronchiectasis. The prevalence of respiratory infections caused by Pasteurella multocida is low, but it is certainly underestimated. Bronchial and/or pleuro pulmonary infections occur in subjects with reduced local and/or systemic defences. The respiratory system is colonized by direct or indirect contagion, usually in contact with pet animals carrying the organism. PMID- 2587898 TI - [Endotracheal prosthesis. A new method of insertion. A case report]. PMID- 2587897 TI - [Pneumocystis pneumonia radiologically simulating tuberculosis]. PMID- 2587899 TI - [New radiological aspects of pneumocystis pneumonia: a diagnostic challenge for the pulmonary specialist]. PMID- 2587900 TI - [Contraception and the risk of genital infections in women]. AB - If the best way of preventing genital infections is probably to restrict the number of partners, physicians should not forget that local contraceptives provide a mechanical or chemical barrier, the protection of which is certainly not ineffective. PMID- 2587901 TI - [Current status of AIDS in gynecology. Recent epidemiologic concepts]. AB - This study reports a particular experiment due to the large proportion of seropositive women followed during pregnancy at the maternity of Nice, where 100 cases were recorded in a little more than two years. The author summarizes the epidemiology and the consequences of the association of pregnancy and AIDS seropositivity. PMID- 2587902 TI - [Contribution of the bacteriology laboratory in genital infections in women]. AB - It is obvious that in order to obtain precise informations from bacteriology in the diagnosis of female genital infections, it is absolutely necessary to respect a number of rules in the sampling method and their transportation. The author summarizes all these restrictions, of which physicians often are not too well aware of. PMID- 2587903 TI - [Urinary infection in women and secondary genital infection]. AB - Urinary tract infections are mainly due to Escherichia coli and certain gynaecological conditions encourage urethral and bladder contamination. The author considers the specific case of pregnant women. PMID- 2587904 TI - [Vulvo-cervico-vaginal infections caused by common (non-herpetic) germs]. AB - The three main types of infections affecting the lower genital tract are due to: Gardnerella, Gonococcus and Chlamydia. The author's text and tables summarize the epidemiology and the management of such infections. PMID- 2587905 TI - [Clinical manifestations of genital herpes in women]. AB - Genital herpes is the frequent localization of a viral disease, the consequences of which on pregnancy are rather ill-known, resulting in excess. The author stresses the advantage of Acyclovir and specifies the management of this problem. PMID- 2587907 TI - Parkinson's disease and the Rhode Island community. PMID- 2587906 TI - [Vulvo-vaginal mycoses]. AB - Vulvo-vaginal mycoses are extremely frequent and relatively easy to treat. Nevertheless, recurrent forms are extremely debilitating and there is no miracle treatment for them. PMID- 2587908 TI - The Rhode Island Task Force on Teenage Suicide Prevention. PMID- 2587909 TI - On medical abbreviations. PMID- 2587910 TI - Surveillance of adolescent suicide attempters in the Rhode Island Hospital Pediatric Emergency Department. PMID- 2587911 TI - Influences on medical students' health beliefs. AB - Physicians' personal health beliefs may have a substantial influence on their attitudes and practice of preventive health care. To assess influences on these health beliefs and gain further insight into these beliefs, a survey containing open ended questions and the Health Locus of Control (HLC) scale was administered to an entire class of medical students at the end of their preclinical training and again after an average of 18 months of clinical training. The most frequent major influence mentioned by preclinical students was medical education/teaching (by 27 per cent) but after clinical training, patients/clinical experiences was cited more often. Although medical students' responses on the HLC were more internal than the theoretical midpoint, they were less internal than persons adhering to exercise programs. Moreover, HLC scores did not change after initial clinical training. These findings suggest that HLC may be established before the clinical years. Nevertheless, medical school has the potential for substantially influencing health beliefs. PMID- 2587912 TI - Hard choices: medical ethics, law and health policy. The discontinuation of life sustaining treatment. PMID- 2587913 TI - Black/white cancer mortality differentials in Rhode Island: inferences for prevention and screening efforts. PMID- 2587914 TI - Lyme disease in Rhode Island. PMID- 2587915 TI - Hard choices: medical ethics, law and health policy. PMID- 2587916 TI - How to get the equipment you want. PMID- 2587917 TI - Assessing a child's chest. PMID- 2587918 TI - Countering Parkinson's assault on your patient's will. PMID- 2587919 TI - What's wrong with this patient? PMID- 2587920 TI - Diabetes now: patient education makes all the difference. PMID- 2587921 TI - How to set up a diabetes education program. PMID- 2587922 TI - A hands-on rehab technique that really works. PMID- 2587923 TI - Legally speaking. Risks of surgery: some are the nurse's. PMID- 2587924 TI - How safe are modified fasts? PMID- 2587925 TI - [What does radiologic diagnosis of the thymus gland accomplish in myasthenia gravis?]. AB - Radiologic imaging in myasthenia gravis is used for the evaluation of pathologic changes of the thymus gland. Computed tomography can demonstrate tumors of the anterior mediastinum in nearly 90% and is therefore superior to conventional radiography. Because of the variety of size and shape of the normal thymus gland, differentiation between normal thymus, follicular hyperplasia and thymoma is rarely possible especially in younger patients. In elderly patients with myasthenia gravis and involution of the thymus gland tumors of the thymus are reliably detected by computed tomography, whereas the ability of computed tomography to predict the histological diagnosis is poor even with intravenous administration of contrast media. PMID- 2587926 TI - [The extragonadal seminoma: a differential diagnosis for mediastinal growth]. AB - The extragonadal seminoma rarely manifests as a mediastinal tumour. It is histologically similar to the testicular seminoma and is often combined with other malformations. The tumour produces signs and symptoms due to its space occupying or infiltrating nature. Radiological methods cannot establish the diagnosis, which is performed by surgery; however, in most of the cases staging is required (thoracotomy). Treatment is possible by surgical excision, irradiation or drug therapy, with an average five-year survival rate of 75%. PMID- 2587927 TI - [Two morphologically different manifestations of a non-Hodgkin's lymphoma in the breast]. AB - The mammographical findings of two woman patients, each with a primarily malignant lymphoma of the breast, are presented. Histopathological assessment revealed in one patient a centroblastic and in the other patient a centroblastic centrocytic lymphoma. No other organs were affected. PMID- 2587928 TI - A rating scale for the severity of psychopathology in children. AB - The Scale for Assessing Severity of the Psychopathology in Children (SSPC) is intended to measure the overall psychosocial impairment caused to children and adolescents by psychic disorders. The scale contains 3 items (number of impaired areas of psychosocial functioning and duration of the modifications of child's behaviour; decrease of school performances below the expected level according to IQ; subjective distress caused by the psychic disorder either to the child or to the family leading to call for medical help) defining a single dimension. Each item is scaled on four degrees of impairment and described behaviourally in a detailed way. The total score summed over the 3 items corresponds to four levels of severity of the psychopathology. Interrater reliability, sensitivity to change and concurrent validity of the SSPC are examined over three studies. PMID- 2587929 TI - Somatosensory evoked potentials in spinal cord diseases. AB - Somatosensory evoked potentials (SEPs) were studied in 115 patients with spinal cord diseases (multiple sclerosis, amyotrophic lateral sclerosis, cervical myelopathy, subacute combined degeneration, myelitis, spinal cord injury, tumours). The SEPs were recorded at three levels: parietal, spinal (cervical or lumbar), and at the Erb point. The central conduction time was also estimated (N9 N13 and lumbar potential (LP): LP-P37). The most sensitive test (95% abnormalities) was represented by the cortical recording of the SEPs when the tibial nerve was stimulated. The interval LP-P37 was increased, the SEPs being delayed or unrecordable and desynchronized (in cases of polyneuropathies only the latency was increased whereas the waveform was normal). In 50 patients with definite form of multiple sclerosis (MS) abnormalities of the cervical potential N13 were obtained in 96% of cases. The cortical SEPs to the median nerve stimulation were abnormal in 64% of cases only (32 patients). Of 10 patients with amyotrophic lateral sclerosis (ALS), cortical SEPs to the lower limb stimulation were abnormal in 6 patients (20%) and only 2 patients had also abnormal N13 and N20. Of 15 patients with cervical myelopathy, SEPs to the tibial nerve stimulation were abnormal and N9-N13 delayed in all but 2 patients. All the 5 patients with subacute combined degeneration had abnormal SEPs to the tibial nerve stimulation. In all the 15 patients with inflammatory spinal cord diseases, the SEPs were abnormal and the central conduction time was delayed. In 5 cases with spinal cord injury the SEPs were absent above the lesion. In 15 patients with tumoral compression SEPs to the stimulation of the nerve dependent on the sensitive root compressed as well as the lower limb SEPs were abnormal. PMID- 2587930 TI - Computed tomography (CT) is effective in the diagnosis of pain recurrency after surgical removal of herniated lumbar disc. AB - The authors analysed CT-scan with intravenous contrast infusion in 18 patients with recurrent pain after lumbar discectomy. CT showed in these patients the cause of recurrency with 100% accuracy, confirmed by reoperation. Contrast enhancement permitted differentiation of postoperative cicatrix from other causes of lumbar spinal canal stenosis. The authors point out that decision about reoperation should be based upon computed tomography examination. PMID- 2587932 TI - Purification of chicken C3 and a structural and functional characterization. AB - A major plasma protein from chicken, analogous to mammalian complement component C3, was purified by the removal of plasminogen, precipitation with polyethyleneglycol, and ion-exchange chromatography. Purification was guided by a rabbit antiserum specific to chicken C3. The yield of native C3 was 27%, and purity and functional activity was assessed by SDS-PAGE, immunoprecipitation techniques, and the ability of the purified C3 to restore the haemolytic activity of C3-depleted chicken serum. Monoclonal antibodies were raised against purified chicken C3. These antibodies were characterized and used to prepare an immunosorbent column to deplete chicken plasma specifically of C3. Chicken C3 has a mol.wt of 185,000-195,000 and a two-chain structure with an alpha chain (118,000) and beta chain (68,000). Complement activation leads to changes in the electrophoretic mobility of chicken C3 and to a decrease in mol.wt to 144,000 corresponding to the release of a 15,000 C3a and a 34,000 C3d/C3dg fragment. Chicken C3 exists in multiple molecular forms with pI values of 6.4-6.6. A genetic polymorphism of chicken C3 based on electrophoretic mobility has not yet been detected after analysis of more than 500 individuals. The function of chicken C3 is dependent on a reactive thioester because treatment of purified chicken C3 with methylamine causes functional inactivation of C3. PMID- 2587931 TI - Dermoid tumour of the fourth ventricle with hyperdense aspect demonstrated on CT scan. Case report. AB - The authors describe the case of a 37-year-old patient, who, after a minor craniocerebral trauma suffered in 1970, was admitted to hospital because of progressive headache, unsteady gait and balance disturbances, deglutition disorders and diplopia. Computed tomography (CT) scan showed a large median hyperdense tumour of posterior fossa with the fourth ventricle involvement. Operation under microscope was performed to remove a considerably large cystic tumour, occupying the fourth ventricle and cisterna magna, displacing the cerebellar lobes and pushing the vermis upward. The tumour was waxy and grey, whereas the cystic liquid had the colour and consistency of oily fluid. The capsule was occluded with the CO2 laser. Postoperative course was good. PMID- 2587933 TI - Functional and molecular characterization of a monoclonal antibody against the 165-186 peptide of human IL-1 beta. AB - A synthetic peptide of human recombinant interleukin 1 beta (hrIL-1 beta) 165 186, which exhibits biological activity in the human fibroblast assay, was used as an immunizing antigen to obtain a murine monoclonal antibody (MoAb) termed FIB 1. This MoAb, an IgG1, reacts specifically with hrIL-1 beta, but not with hrIL-1 alpha, as measured in enzyme-linked immunosorbent assays (ELISA). The MoAb FIB 1 detects the characteristic 17 kDa IL-1 protein in Western blots. Binding to the antigen is specific, as deduced also from the close correlation of ELISA immunoreactivity with IL-1 biological activity. The anti-IL-1 beta 165-186 Ab specifically neutralizes the biological activity of hrIL-1 beta and native IL-1, as measured by the IL-1-induced proliferation of murine thymocytes and human fibroblasts and the IL-1-dependent IL-2 production by murine T cells (EL4-6.1). Fifty per cent of hrIL-1 beta activity (25 U/ml, or 0.25 ng/ml) has neutralized by less than 30 micrograms/ml of MoAb. Furthermore, FIB 1 recognizes intracellular IL-1 in lipopolysaccharide-stimulated human peripheral blood mononuclear cells. The anti-IL-1 beta 165-186 Ab does not react with the shorter IL-1 beta fragment 161-173 in solid-phase ELISA, therefore the binding region seems to be localized in the amino acid sequence VALGLKEKNLYLS. A sandwich-ELISA, using a polyclonal sheep anti-IL-1 beta 251-269 Ab as the capture antibody and an anti-IL-1 beta 165-186 MoAb as the detecting probe, allowed the determination of IL-1 beta from crude culture supernatants. PMID- 2587934 TI - A monoclonal antibody, H2, defines a new surface antigen expressed on human lymphocytes. AB - We have previously described a monoclonal antibody (MoAb), H2, which recognized a tumour-unique antigen on a human T-cell chronic lymphatic leukaemia (T-CLL, CD3,4+). However, further characterization of H2 has revealed a reactivity with the majority of T lymphocytes and a minority of B lymphocytes, some malignant T cells and a few cell lines of leukaemia or of hematopoietic tumour origin. The molecular weight of the antigen (80,000) precipitated by the MoAb H2 from the cell lines NALM-6 and Reh corresponded to that previously found. When PBL were stimulated with PHA, IL-2, or Con A a reduced reactivity of H2 could be seen. The MoAb H2 was submitted to the Fourth International Conference on Human Leucocyte Differentiation Antigens, Vienna, 1989. H2 did not cluster in any of the 78 clusters of differentiation (CD 1-78) discussed at the conference, indicating its unique reactivity. This suggests that we have defined a new antigen on lymphocytes with a possible role along the resting-proliferating axis. PMID- 2587935 TI - Synovial fluid from rheumatoid arthritis patients induces polyclonal antibody formation in vivo. AB - Our previous studies demonstrated the presence of a T-cell replacing factor in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) and that RA-SF can activate, selectively, the induction of IgG2b antibody secreting cells in lipopolysaccharide (LPS)-pretreated mouse spleen cell cultures. In the present study the effect of RA-SF was tested in vivo in mice. Injection of the polyclonal activator LPS induced the production of IgM and IgG3 secreting cells in normal mice. However, the addition of RA-SF led to a selective increase in the production of IgG2b with a peak response on day 5 and IgG1 plaque-forming cells (PFC) with a peak on day 7. Neither the IgG2b nor IgG1 responses were caused by specific immunity against heterologous proteins present in RA-SF, as injection of in vitro inactive RA-SF samples did not induce PFC. The effect on B cells of RA SF was further evaluated by injection of RA-SF in combination with LPS to the Xid B-cell deficient CBA/N mice. RA-SF had identical effects in CBA/N as in normal mice. The biological implication of these findings is discussed. Our earlier results support the idea that B cells are endogenously activated in RA patients. We have speculated that this activation is caused by the B-cell differentiation factor which is present in SF. Therefore, we also tested whether RA-SF could influence antibody-forming cells in mice that spontaneously develop autoimmunity. We found that injection of RA-SF alone, in the absence of any other activating substance, induced a very marked increase of IgG producing cells in (NZW x NZB) F1 hybrid mice. From a relatively high background level the RA-SF could still induce an up to 100-fold increase in the numbers of PFC in spleens of such mice. PMID- 2587936 TI - Massive vascular AA-amyloidosis: a histologically and biochemically distinctive subtype of reactive systemic amyloidosis. AB - Amyloid protein AA consists of several subspecies which mainly arise through proteolytic cleavage at various sites of the precursor, serum protein AA. The most common protein AA subspecies (the protein AA prototype) contains 76 amino acid residues. In previous studies we have shown that distinctive patterns of amyloid infiltration occur in AA-amyloidosis. The amyloid in different patterns of infiltration seems to consist of distinctive protein AA subspecies. In the present study we have analysed protein AA in three patients with a form of AA amyloidosis with heavy vascular infiltration and show that the amyloid fibrils contain two groups of protein AA subspecies. One, quantitatively predominating, group contains large subspecies of up to 94 amino-acid residues and a second group of protein AA-molecules contains around 50 amino-acid residues. The AA molecules lack the N-terminal arginine residue. It is concluded that AA amyloidosis with massive vascular infiltration is a distinctive subform with typical clinical and histological appearance and with fibrils containing characteristic protein AA subspecies. PMID- 2587938 TI - The twentieth annual general meeting of the Scandinavian Society for immunology. Copenhagen, Denmark, 19-22 June 1989. Abstracts. PMID- 2587937 TI - Characterization of PPD-specific T-cell lines generated in type I (insulin dependent) diabetic and healthy individuals. AB - The particular susceptibility to insulin-dependent diabetes mellitus (IDDM) conferred by HLA-DR3,4 heterozygosity has been suggested to be an effect of transcomplementation of HLA class II molecules. To test this hypothesis of special IDDM-specific hybrid determinants and to evaluate the T-cell repertoire towards a specific antigen in IDDM patients we generated a total of 352 PPD specific T-cell lines by the soft-agar cloning technique and studied their restriction by HLA class II molecules. Of these lines, 227 were from nine IDDM patients, of whom six were DR3,4 heterozygotes, and 125 from 10 healthy controls. Forty-six T-cell lines elicited specific responses in at least two experiments and in addition to T-cell lines demonstrating class-II-restricted PPD specificity, lines with an alloreactivity occurred. HLA-DQ-restricted PPD specific T-cell lines were not identified and a possible DP restriction (DPw2) was only observed with one line. These data indicate that PPD is preferentially presented to T cells in the context of HLA-DR/Dw. Presentation of PPD by hybrid molecules in IDDM patients or by IDDM-specific class II epitopes recognized by the T-cell lines was not demonstrated. By restriction fragment length polymorphism analysis using a probe for the joining region of the T-cell receptor gamma gene, T-cell lines generated by the soft-agar cloning technique were found to be oligoclonal. It is concluded that soft-agar cloning should be followed by subsequent limiting dilution in order to assure monoclonality. Different preparations of antigen-presenting cells (APC) were tested. In several cases the T-cell lines were not able to respond to PPD presented by Epstein-Barr-virus transformed lymphoblastoid cell lines (LCL). It was demonstrated that lipopolysaccharides (LPS) of E. coli potently reduce the proliferative response of antigen-specific and alloreactive T cells when T-cell-depleted peripheral blood mononuclear cells (E- cells) were used as APC, whereas only limited inhibition was observed when LCL were used as APC in the presence of LPS. This effect of LPS is suggested to be mediated by increased prostaglandin secretion by monocytes among the E- cells since indomethacin abolished the effect of LPS. This observation may have implications for T-cell cloning procedures since we have found that most commercially available culture media are heavily contaminated with endotoxin. PMID- 2587939 TI - The outcome of Pneumocystis carinii pneumonia in Danish patients with AIDS. AB - A total of 100 consecutive patients with AIDS were evaluated for efficacy and safety of treatment and secondary prophylaxis directed against Pneumocystis carinii pneumonia (PCP). 89 episodes of PCP were recorded in 75 patients. 63 of the 75 patients (84%) with a first episode of PCP were discharged. Of 72 patients with a first episode of PCP who were initially treated with trimethoprim sulfamethoxazole. 76% completed therapy successfully. Side effects were common, but generally mild and tolerated during continued treatment. 7/11 patients (64%) with a first episode of PCP who required mechanical ventilation were discharged. Long term prognosis for these patients was not worse than for patients who did not require mechanical ventilation. Relapse of PCP occurred in 3/50 patients (6%) during secondary prophylaxis, 160 mg trimethoprim and 800 mg sulfamethoxazole (TMP-SMZ) every 24 h, compared to 11/16 (69%) patients who were not receiving prophylaxis (p less than 0.00001). No patients discontinued prophylaxis because of side effects. It is concluded that for most patients with AIDS and PCP, treatment and secondary prophylaxis with TMP-SMZ is safe and effective. PMID- 2587940 TI - Pneumocystis carinii pneumonia in Stockholm, Sweden: treatment, outcome, one-year follow-up and pyrimethamine prophylaxis. AB - In 33 consecutive AIDS patients with a first episode of Pneumocystis carinii pneumonia (PCP) we evaluated treatment, outcome, recurrence rate and pyrimethamine as chemoprophylaxis in a 1-year follow-up. Only 2 patients had a CD4 lymphocyte cell count greater than 0.2 X 10(9)/l. Trimethoprim sulfamethoxazole (TMP-SMX) was initially given to 32 patients but in 20 of these patients severe adverse reactions caused us to discontinue treatment. Of these 20 patients 11 were started on i.v./i.m. pentamidine but in 6 adverse reactions forced us to withdraw pentamidine. Patients were retrospectively divided with regard to duration of therapy into 2 groups. We could not find any difference between patients in Group 1 treated for less than or equal to 14 days and patients in Group 2 treated for greater than 14 days when comparing outcome, number of recurrences and mean time until recurrence. In 16/21 patients given only TMP-SMX initially in a high dose (means = 16 mg trimethoprim/kg/day), dose reduction was performed to means = 10.5 mg trimethoprim/kg/day after a mean time of 6.9 days. The case-fatality rate for these patients was 10% (2/21) and the overall case-fatality rate was 15% (5/33). We chose pyrimethamine (50-175 mg/week) as secondary prophylaxis for PCP. At 1-year follow-up another 16 patients had died (21/32) and 9/27 (33%) discharged patients had had one recurrence each of PCP. All recurrences occurred among patients treated with only TMP-SMX for the acute episode of PCP. Of these 27 discharged patients 23 had been given pyrimethamine and 8 (36%) of these had experienced a recurrence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2587941 TI - P blood group and proneness to urinary tract infection in Japanese children. AB - The globoseries of glycolipids are antigens in the P blood group system as well as epithelial cell receptors for uropathogenic Escherichia coli. The P1 blood group is overrepresented in Swedish girls with recurrent pyelonephritis. In this study, Japanese children with urinary tract infection (UTI) were analyzed for P blood group phenotype. Out of 26 children with recurrent UTI, 50% were of the P1 blood group compared to the 31% of P1 individuals in the Japanese population at large (p less than 0.05). Of children defined as having febrile UTI 62% were P1. The P1 blood group was thus significantly enriched (3.5 times) in the children with febrile UTI. These results support the hypothesis that individuals of blood group P1 run an increased risk for recurrent pyelonephritis. PMID- 2587942 TI - Evaluation of a bioluminescence assay for the detection of bacteriuria. AB - Bacteriuria defined with urine culture as the reference method was compared with bacterial adenosine triphosphate (ATP) measurements of cystoscopical urine samples from 216 men. Discrepant samples were studied by reculturing and microscopy of the sediment. Results show a good correlation (sensitivity 1.0 and specificity 0.95) between bacteriuria greater than or equal to 10(4) cfu/ml and bacterial ATP greater than 10 nmol/l measured by bioluminescence. Samples with macroscopic hematuria may influence the ATP value and give false positive results. PMID- 2587943 TI - The role of shigella spp. in childhood diarrhoea in Iran and their antibiotic resistance. AB - The incidence of shigellae was measured in 445 children with diarrhoea in Sanandaj, Kordestan, and 715 in Tehran during a 1-year study. 18 (4%) patients in Sanandaj and 41 (5.7%) patients in Tehran were positive for various shigella species. Sh. boydii (7 strains) and Sh. sonnei (25 strains) were the commonest species in Sanandaj and Tehran respectively. Among the isolates from Sanandaj the highest resistance was to tetracycline (55.5%), whereas in Tehran it was to sulfamethoxazole/trimethoprim (68.3%). PMID- 2587944 TI - The influence on the secretory IgA antibody levels in lactating women of oral typhoid and parenteral cholera vaccines given alone or in combination. AB - 41 lactating Pakistani women were vaccinated orally with Salmonella typhi vaccine alone or in combination with parenteral Vibrio cholerae whole cell vaccine, in order to study the possible difference in the secretory response after live and inactivated vaccines. The antibody response in saliva, milk and serum was recorded using the enzyme-linked immunosorbent assay, ELISA. All had prevaccination antibody levels against the 2 vaccines. The live S. typhi vaccine gave a serum IgG and IgA response but did not influence the IgM levels. Salivary or milk secretory IgA (SIgA) antibody levels showed both increases and decreases but in most cases remained unchanged. Even if the vaccine was given in enteric coated capsules, the milk and salivary SIgA response was more often decreased than increased, although somewhat higher serum IgG levels were attained with this preparation. Parenteral cholera vaccination enhanced both serum and SIgA milk antibody response. Combination of the 2 vaccines did not have any untoward effect on the antibody response in serum or in secretions against V. cholerae or S. typhi LPS. The results show that an oral vaccine often induces a rather poor, or even negative mucosal antibody response, while a parenteral vaccine provokes a substantial SIgA response in individuals orally primed by natural exposure. This is in agreement with our previous findings with oral and parenteral poliovirus vaccines in this population. PMID- 2587945 TI - Immune status and booster effects of low doses of diphtheria toxoid in Swedish medical personnel. AB - During a diphtheria outbreak among Swedish alcoholics in 1984-1985, only 60% of 328 medical staff at risk for exposure had diphtheria antitoxin titers greater than or equal to 0.01 IU/ml, which is usually considered to give relative protection. 21% had levels between 0.01-0.09 IU/ml and the remaining 39% had titers greater than or equal to 0.1 IU/ml. Booster doses of 0.5 Lf-12.5 Lf of diphtheria toxoid were given to 450 vaccinees. Of 72 individuals with low pre immunization titers, who were immunized with less than or equal to 2.5 Lf diphtheria toxoid, 40% failed to reach greater than or equal to 0.1 IU/ml when analyzed 4 weeks after vaccination. Local tenderness and swelling greater than 5 cm at the site of injection or general discomfort was found in 11% of those immunized with low dose diphtheria toxoid (less than or equal to 2.5 Lf). When the dose 0.5 Lf of diphtheria toxoid was combined with tetanus toxoid (3.75 Lf) the frequency of adverse reactions increased to 34% (p less than 0.001). The study shows that vaccination status in medical personnel must also be continuously examined in countries where diphtheria is rare and that low booster doses of diphtheria toxoid may not achieve an adequate immune response. PMID- 2587946 TI - Changes in erythrocyte sedimentation rate, C-reactive protein and hematological parameters in patients with acute malaria. AB - Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and routine hematological parameters were reviewed in 258 patients with acute malaria and compared to a control group of 120 patients with other febrile illnesses after visiting malaria endemic areas. Thrombocytopenia was found in 80% of the malaria patients compared to 13% in controls (p less than 0.01). The malaria patients also had lower white blood cell counts and marginally lower hemoglobin values than control patients. No major differences were found in ESR or CRP values. Furthermore, there were no major differences in the hematological parameters between patients infected with different malaria species, or between patients with different ethnic background. Thrombocytopenia (platelet count less than 150 x 10(9)/l) had a predictive value positive of 56% and a predictive value negative of 95% for malaria in a febrile patient coming from an endemic area. Thus, the risk of malaria in a febrile thrombocytopenic patient coming from an endemic area was 56%, while the risk that another patient with a normal platelet count still had malaria was 5%. PMID- 2587947 TI - A prospective study of infectious morbidity and antibiotic consumption among children in different forms of municipal day-care. AB - During the 9-month period September 1986-May 1987, reasons for absence and antibiotic consumption were investigated among children cared for in day-care center(s) (DCC) and Swedish town. family day-care (FDC) within a limited geographical area of a medium-sized Swedish town. All 352 children in 11 DCC in this area and 199 children in FDC were included in this prospective study, which intended to elucidate the infectious morbidity. The investigation period comprised 55,760 and 26,019 expected days' attendance for the DCC and FDC children, respectively. A higher absence attributable to infection was evident at all ages in DCC children than in those in FDC. This difference tended to diminish with age. No difference in antibiotic consumption was evident between the 2 categories, and the diagnostic pattern was almost identical. In the DCC, overall absence figures, and absence due to infection, were considerably lower than in earlier comparable studies. Appreciable differences in absence due to infection and antibiotic consumption were also found between different "departments" in the DCC; both low and high-absence groups could be identified. There was an indication of differences between the groups both socially and in the environment at the DCC. PMID- 2587948 TI - Fatal outcome of echovirus 7 infection. AB - A 9-month-old boy died of a disseminated echovirus 7 (E7) infection with virus being cultured from his liver and spleen. His hepatic failure was complicated by candidiasis and marrow hypoplasia and aggravated by a possible immune deficiency. PMID- 2587949 TI - Severe encephalitis associated with disseminated echovirus 22 infection. AB - Severe encephalitis associated with disseminated echovirus 22 infection occurred in a previously healthy 5-month-old boy. Echovirus 22 was diagnosed by a seroconversion both in serum and cerebrospinal fluid and by isolation of the virus from several stool samples. The child damaged severely and at the age of 8 1/2 months infantile spasms developed. PMID- 2587950 TI - Folate supplements and the treatment of cerebral toxoplasmosis. PMID- 2587951 TI - Serratia bacteremia: a review of 44 episodes. AB - This report reviews 44 episodes of serratia bacteremia over a 9-year period (1980 1988) in a community-teaching hospital in the USA. The median age of patients was 64 years and 34% of the patients were older than 70 years. Nosocomial acquisition of bacteremia occurred in 70% of episodes, and 11% of patients were admitted from nursing homes. Nine episodes (20%) were polymicrobial bacteremia. The major portals of entry were the lower respiratory tract (11 episodes) and the urinary tract (6 episodes). The overall mortality was 52%. Factors that adversely influenced the mortality rate were rapidly fatal and ultimately fatal underlying conditions (p less than 0.001), platelet counts less than or equal to 100 x 10(0)/l at the onset of bacteremia (p less than 0.01), and total serum bilirubin greater than 18 mumol/l at the onset of bacteremia (p less than 0.01). All serratia strains tested were susceptible to gentamicin, kanamycin, amikacin and ceftizoxime. PMID- 2587953 TI - Dermatitis of the face, yellow toe nail changes, hairy leukoplakia and oral candidiasis are clinical indicators of progression to AIDS/opportunistic infection in patients with HIV infection. AB - In a prospective longitudinal study of 89 men with HIV infection and persistent generalized lymphadenopathy (PGL) we tried to find clinical signs predictive of development to AIDS/opportunistic infection (OI). The mean observation time was 47 months. 27 patients (30%) developed AIDS/OI after a mean of 37 months. The estimated median time from diagnosis of PGL to AIDS/OI was 68 months. Four clinical signs of progression towards AIDS/OI were identified: dermatitis of the face, yellow toe nail changes, hairy leukoplakia and oral candidiasis. One or more of these signs were recorded in 25/27 (93%) of the patients before the development of AIDS/OI. The estimated median time from registration of each sign to AIDS/OI was: dermatitis of the face, 29 months; yellow toe nail changes, 21 months; hairy leukoplakia, 18 months; and oral candidiasis, 10 months. The estimated median time from herpes zoster to AIDS was only slightly shorter than the estimated time from diagnosis of PGL to AIDS/OI. PMID- 2587952 TI - Serological markers of primary HIV infection. AB - 39 persons with an incidentally discovered seroconversion from HIV antibody negative (Ab-) to antibody positive (Ab+) state as measured by an enzyme-linked immunosorbent assay (ELISA) were investigated for the presence of (1) HIV antigen (Ag) and (2) immunoblotting test (IBT) Ab in serum samples collected within the year before seroconversion. 13 (33%) of the patients were HIV Ag+ at some time before seroconversion. However, the collection of samples was not done systematically and the samples from patients who had at least 1 sample collected within 3 months before seroconversion were thus compiled separately. This group consisted of 58 samples from 19 patients and among these none were HIV Ag+ earlier than 11 weeks before seroconversion, but the prevalence of HIV Ag+ samples was rising towards seroconversion and 10 patients (53%, 95% confidence limits: 29-76%) became HIV Ag+ in this 11-week period. Further, among all patients 13 (33%) were IBT Ab+ 4-50 days (median: 14 days) before seroconversion. Finally, among 18 patients with signs and symptoms consistent with an acute HIV infection 10 were HIV Ag+, as opposed to 4 HIV Ag+ patients among 21 without symptoms (p = 0.041). PMID- 2587954 TI - The etiology of bacterial cellulitis as determined by fine-needle aspiration. AB - Bacterial cellulitis is a common problem, etiologic diagnosis often unrewarding and opinions differ on empiric therapy. The purpose of this study was to determine the major microbiologic causes of bacterial cellulitis in a walk-in Emergency Room setting. 94 cases in 89 patients with clinical signs of cellulitis were studied. The infection was closed in 74 cases and associated with an open skin lesion in 22. The infection site was aspirated with a suction air-buffer technique employing a Cameco handle for easier handling and stabilization of the aspiration needle. After exclusion of contaminated samples, positive cultures were obtained from 30 cases (31.9%). Cultures were positive in 30.6% of open lesions and in 36.4% of closed ones. Staphylococcus aureus was the most common organism, present in 11 cases, S. epidermidis in 8 and group A beta-hemolytic streptococci in 5. All S. aureus strains were methicillin-sensitive and only 1 was sensitive to penicillin. The most common site of infection was the lower extremity (59%). According to these data the optimal initial therapy for bacterial cellulitis in adults should be with drugs active against both staphylococci and streptococci. PMID- 2587955 TI - The value of C-reactive protein as a marker of bacterial infection in patients with septicaemia/endocarditis and influenza. AB - In order to evaluate the capacity of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC) and polymorphonuclear neutrophils (PMNs) to differentiate between bacterial and viral infection we studied 176 patients with septicaemia/endocarditis (SE), 59 patients with uncomplicated influenza (UI) and 22 patients with complicated influenza (CI) retrospectively. All 4 parameters were significantly more elevated in SE and CI than in UI. Among patients with SE 10 176 had a CRP value less than 50 mg/l and in patients with UI 5/56 had a CRP value greater than 100 mg/l. Patients with SE caused by pneumococci had the highest CRP levels and patients with alfa haemolytic streptococci the lowest. The sensitivity and specificity favours the use of CRP as an indicator of bacterial superinfection in influenza. PMID- 2587956 TI - Use of antibiotics in general practice in Denmark in 1987. AB - The worldwide usage of antibiotics is increasing making detailed information on prescribing patterns and intervention methods necessary. This investigation focused on the general practitioner's (GP's) usage of antibiotics in Denmark. Information on 7,607 patients treated by 602 GP's during 1 week in March 1987 were collected. The most commonly treated infectious diseases were upper respiratory tract infections (40%) and lower respiratory tract infections (17%). Penicillin was by far the most frequently prescribed antibiotic (44%), followed by antibiotics used locally (17%) and ampicillins (14%). Compared with previous investigations, this result indicated a relative increase in prescription of penicillin during recent years. The mean number of daily dosages was 2-3 and the duration of treatment 6-7 days, with ampicillin generally given 1 day longer than penicillin. The differences between prescribed daily dosages (PDD) found and defined daily dosages (DDD) ranged from + 40% to - 50%, making estimations of numbers of treated patients from total usage of antibiotics in DDD/1,000 inhabitants/day impossible. PMID- 2587957 TI - Yeasts in blood cultures: impact of early therapy. AB - Patients with growth of yeast in blood cultures were analyzed during the 6-year period 1981-1986, with special regard to predisposing factors, mortality, severity of the disease and therapy. There were 80 isolations of yeasts in blood cultures in 39 patients and Candida albicans was the most common. The majority of the patients in the material had multiple predisposing factors. The overall mortality was 58%. Patients with d disseminated disease had a mortality of 79% in contrast to 32% in patients with transient fungemia. Disseminated disease was more common in surgical patients. The prognosis of patients treated within 4 days from the onset of septic symptoms was significantly better than that of patients with a later start of therapy. On the basis of these results we emphasize the importance of early empiric therapy. PMID- 2587958 TI - Pasteurella multocida occurs in a high frequency in the saliva of pet dogs. AB - Pasteurella multocida is a frequent cause of infection after animal bites. In contrast to earlier reports, P. multocida appeared to be as common among dogs as among cats. We found 17 (81%) of 21 pet dogs to harbour P. multocida in their saliva. At normal contact, the risk of transmission from dogs to humans seems to be negligible. Only 1/27 dogs owners was found to harbour the organism. None of 13 cat owners or 23 persons without animal contacts harboured P. multocida. PMID- 2587960 TI - Current trends in anaerobic infections. Proceedings of the Third European Congress on Anaerobic Bacteria and Infections. Munich, March 8-10, 1989. PMID- 2587959 TI - Acyclovir crystalluria. PMID- 2587961 TI - Mechanisms of antimicrobial resistance in anaerobic bacteria: the predictive approach. AB - Antibiotic resistance in anaerobic bacteria probably evolves from broadly undetected mechanisms of resistance, as the generally accepted breakpoints in susceptibility testing are mainly based on pharmacological grounds. Some of the strains considered susceptible by conventional techniques may harbour mechanisms of resistance. These resistant organisms should be screened using the antibiotic concentrations immediately above those inhibiting the fully susceptible population of a given species as breakpoints. The following break-points for bacteroides strains are suggested as definitions of the entirely susceptible population: piperacillin 8 mg/l; ceftizoxime 8 mg/l: cefoxitin 8-16 mg/l: imipenem 1 mg/l: ticarcillin-clavulanate 2 mg/l; clindamycin 1 mg/l: chloramphenicol 8 mg/l: tetracycline 4 mg/l: metronidazole 1 mg/l. Detection of an increased frequency of organisms presenting low-level resistance may be useful to predict and possibly control the appearance and spread of fully resistant anaerobic organisms. PMID- 2587962 TI - Immune mechanisms in the prevention of intra-abdominal abscess formation. AB - Bacteroides fragilis is the most commonly isolated anaerobe from intraabdominal infections. In experimental models of intraabdominal sepsis, B. fragilis has been shown to be uniquely virulent. Some of these virulence traits are due to the capsular polysaccharide of this organism. Immunity to infection secondary to B. fragilis seems to involve both arms of the immune system. Humoral immunity (complement, antibody and PMNs) is critical to clearance of these bacteria from the blood stream. Cellular immune mechanisms predominate against intraabdominal abscess formation. Adoptive transfer experiments have shown that a CD8+, IJ+, non H2 restricted immune T cell or lysate from this T cell confers protection to immunocompetent, naive mice. An in vivo system has been developed to begin defining the mechanism of protection. B. fragilis placed inside a filter containment chamber within the peritoneum of immune mice are specifically killed over an 8-day period in the absence of white blood cells. This killing phenomenon was also observed inside filter chambers within mice receiving adoptively transferred immune T cells or lysates of these T cells. Furthermore, killing is specific to B. fragilis. These results support a T cell dependent mechanism for killing this bacteria and provide an interesting model for further exploration. PMID- 2587963 TI - [Additive substances for drinking water. Legal basis for the requirements]. PMID- 2587964 TI - Predictions of developmental patterns during infancy: assessments of children 0-1 years. AB - The present study investigated how neonatal behavioural organization was related to later mental development during the first year of life. The study further investigated the relationship between early social affective behaviour and later mental development. A group of 40 infants was assessed five times during the infants' first year, at three and 14 days and at four, eight and 12 months. The Brazelton Neonatal Behavioural Assessment Scale (NBAS), the Duve method (a clinically based method for observation of social affective behaviour), and Griffiths' Mental Development Scales were used to assess the development of the infants. The results indicate that early predictive behavioural components can be identified. Neonatal state control capacity was related to motor development at both eight and 12 months. Social responsitivity at four months was related to hearing and speech at eight as well as at 12 months. The NBAS dimensions were good predictors of eight months performance, but were poor predictors of 12 months performance. PMID- 2587965 TI - Dark-adaptation mechanisms of the long-wave foveal cones. AB - The ordinary long-term rod and cone dark-adaptation curves have generally been assumed to follow a single exponential rate of recovery. However, in two previous papers on rod dark-adaptation (Stabell et al., 1986a, b), the recovery curve was found to consist of three different sections. The results of the present paper show the same type of recovery function with three different sections for the long-term dark-adaptation curve of the long-wave cone system. During the major, middle section log cone threshold, like log rod threshold, is linearly related to the logarithm of the concentration of bleached photopigment. Presupposing that the bleached cone photopigment acts as a ligand, the change in threshold level obtained during the middle section of the dark-adaptation curve is well described by the change in activity rate of an allosteric, postively cooperative enzyme built as a dimer. PMID- 2587966 TI - Consistency in synesthetic experience to vowels and consonants: five case studies. AB - The present study attempted to specify the actual degree of consistency in synesthetic experience in two synesthetes and three non-synesthetes. By comparing colour chip selections, and size and density ratings, to the same set of stimulus letters on separate occasions, it was found that the synesthetic subjects showed a high consistency in responding over a short (24 hours) as well as a long (one year) time span. In comparison, the non-synesthetic subjects demonstrated less consistent responding when retested after 24 hours. However, the differences between the two groups were smaller than expected. Consistency to vowels and consonants was compared, and it was found that consistency to consonants was comparable to, or even higher than, vowel consistency in all subjects. PMID- 2587967 TI - [Rare vascular complications of Behcet's disease (so-called angiobehcet)]. AB - Vascular involvement in Behcet's disease is rare and may cause life-threatening complications. We report on 3 patients who presented with vascular problems in the course of the illness. (1) A 37-year-old woman suffered multiple pulmonary artery aneurysms (PAA) 3 years after the first symptoms of Behcet's disease (BD) had been noted. They completely regressed under three-month high-dose corticosteroid therapy and remission has lasted now for 2 years. (2) The second patient, a 22-year-old man, developed 2 vascular complications of BD: first (1986 1987), he was shown to have a sinus venous thrombosis which resolved under prednisone and oral anticoagulation therapy. Then (1988) he presented with multiple large PAA and high fever. Despite marked radiological regression of the multiple PAA under high-dose prednisone treatment, he remained symptomatic. Repeated hemoptysis in September 1988 prompted us to add cyclosporine A in a dosage providing whole blood levels of 250-350 ng/ml. Four months later pulmonary radiological studies had normalized, but manifestations of BD on the skin and mucosa remained unchanged. 7 months after starting Cy A therapy the patient died suddenly of massive hemoptysis. (3) The third patient, a 23-year-old Spanish immigrant, had a diagnosis of BD when presenting with sinus thrombosis. Later he underwent surgery 3 times for false aneurysms of the common femoral artery which developed at the site where he had been punctured for angiography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2587968 TI - [DNA diagnostics in hemophilia A and B]. AB - Carrier detection and prenatal diagnosis of hemophilia A and B are possible with cloned factor-VIII:C- and factor-IX-gene-specific or linked probes which detect restriction fragment length polymorphisms (RFLPs). In this study, 12 hemophilia-A and 5 hemophilia-B-families were studied to identify carriers and provide adequate genetic counselling to women who were heterozygous for one or more of the intragenic or linked DNA probes with respect to future pregnancies. PMID- 2587969 TI - [Visceral leishmaniasis (kala-azar) as an opportunistic infection in immunosuppressed patients]. AB - The occurrence of visceral leishmaniasis is rare in Switzerland. We discovered this disturbance in a patient while on immunosuppressive medication for mycosis fungoides. Untreated visceral leishmaniasis has a high mortality. It can be expected that more cases will be observed in patients treated with immunosuppressive drugs or in patients with the acquired immunodeficiency syndrome (AIDS). PMID- 2587970 TI - [Comparative study of 2 in vitro screening tests for the diagnosis of allergy]. AB - In 108 patients with inhalant disorders, atopy screening was performed with two in-vitro tests; Phadiatop (Pharmacia) and inhalant screening (IHS 1 and 2 discs) (Kallestad). Both tests are accurate and useful tools in differentiating atopics from non-atopics. In contrast to the Phadiatop the allergens on the IHS discs are known, and thus if the results are positive single RAST detection is possible. PMID- 2587971 TI - [A peculiar abnormality of the fallopian tube: induced by embryonic kidney tumor?]. AB - A 17-year-old female with severe pain of the midabdomen was found to have a retroperitoneal cystic tumor, an ectopic ovary and a fallopian tube without fimbriated end. An attempt is made to determine whether these early embryonic malformations could be traced to a common origin. This is possible provided that the tumor is regarded as a mesonephroma. A histological study of the normal development of the Mullerian duct was performed utilizing human embryonic series. Previous development theories and more recent investigations are discussed. Malformations of the tube described in the literature and possible etiologies are summarized. PMID- 2587972 TI - [Giant adenoma of Brunner's glands]. AB - Bleeding, obstruction and invagination are the common symptoms of large polyps in the duodenal bulb. We present 2 patients with a large ulcerated Brunner's gland adenoma. The clinical findings were acute bleeding and nonspecific upper gastrointestinal symptoms. The treatment was surgical due to a suspect histological finding in one case, a thick stalk in the other, and the fact that endoscopic polypectomy is a much higher risk procedure in the duodenum than in the colon. PMID- 2587973 TI - [The value of modern biology for the clinical practice of medicine. Symposium of the Swiss Academy of Medical Sciences. 14-15 September 1989, Basel. Abstracts]. PMID- 2587974 TI - [Alternative methods: development and use of two "in vitro" models for endocrine studies]. AB - Most endocrinological studies are normally performed on several animal groups: one group for the determination of hormonal levels in tissues and plasma under basal conditions, a second group for the same determinations after "in vivo" treatment of the animals (stimulation or inhibition of the endocrine activities) and two additional groups for morphological investigations. Surgical approaches belong not rarely to the "in vivo" treatment of the animals. Moreover, the results from the different animal groups have to be extrapolated. In order to overcome these drawbacks, we have developed two "in vitro" models by means of which we can study on the tissues from the same animal: 1. function and structure of the hypothalamus and 2. function and structure of isolated pituitary cells. By using these models we can considerably reduce the number of animals needed for the studies, replace the "in vivo" by the "in vitro" experiments and refine the methods avoiding, among others, the extrapolation of results. PMID- 2587975 TI - [Experimental infection of calves and sheep with bovine Giardia isolates]. AB - 9 Giardia-free calves were artificially infected with 1.5-5.1 x 10(6) Giardia cysts originating from Swiss cattle ("bovine isolates"). In 4 of these animals the course of infection was examined. After prepatent periods of 7-8 days all calves excreted high numbers of Giardia cysts for 60-112 days. During patency on 44% of the examination days Giardia cysts and antigen could be detected simultaneously in faecal samples using the flotation method and a sandwich-ELISA, respectively. With the exception of light diarrhoea lasting only for some days at the beginning of patency no other symptoms occurred. Further 5 artificially infected calves were submitted to autopsy. Giardia trophozoites were detected in 4 calves in the jejunum and in 1 animal in the ileum (peroxidase-antiperoxidase method). All animals were simultaneously infected with Campylobacter spp. and/or Rota- and Corona-virus. Electronmicroscopically mucosal attachment sites of Giardia trophozoites had intact microvilli and enterocytes. In various parts of the intestine blunting and flattening of the villi and cellular infiltrations of the mucosa were present. These alterations in calves are generally associated with bacterial and/or viral infections of calves. A Swiss bovine Giardia cyst isolate was transmitted to 4 Giardia-free conventionally maintained lambs which excreted Giardia cysts after prepatent periods of 10-21 days for 31-61 days. PMID- 2587976 TI - The woolly monkey (Lagothrix lagothricha): a possible model for human hypertension research. AB - The anatomical-pathological findings of 15 woolly monkeys were comparable with those described in man with essential benign or malignant hypertension. Kidneys revealed arterio- and arteriolosclerosis or an onion peel-like proliferation, in some cases necrotizing endarteritis. Obesity due to restricted physical activity, unnatural feeding, and psychical and physical stress could have contributed to the development of this condition. Further, high vulnerability of the genus woolly monkey is postulated. Thus, essential hypertension of woolly monkeys appears to be a multifactorial disease. PMID- 2587977 TI - [What is your diagnosis? Which treatment do you suggest? Colonic obstruction in a calf]. PMID- 2587978 TI - Primate bites in Gibraltar--minor casualty quirk? AB - In one year 55 patients presented to the casualty department of St Bernard's Hospital, Gibraltar, with a primate bite. The implications of such wounds on the health of these patients is contrasted with the morbidity and mortality associated with primate bites in the African subcontinent. PMID- 2587979 TI - Fine needle aspiration cytology of lesions of the head and neck and factors affecting outcome. AB - Fine Needle Aspiration Cytology (F.N.A.C.) has been used as a diagnostic tool by the ENT departments in Tayside since the end of 1985. This paper discusses the results of our initial experience with this and outlines some of the diagnostic pitfalls. This is a useful and accurate procedure with many advantages over diagnostic biopsy. PMID- 2587980 TI - The hyperthyroidism of polyostotic fibrous dysplasia--a possible autoimmune aetiology. AB - Endocrine disorders are a relatively common accompaniment of polyostotic fibrous dysplasia. Considerable debate has taken place concerning possible responsible mechanisms. This case demonstrates that the hyperthyroidism associated with the condition is of thyroidal origin and of probable autoimmune aetiology. PMID- 2587981 TI - Hyperkalaemic periodic paralysis and HELLP syndrome: an unusual combination. PMID- 2587982 TI - Minor aphthous oral ulceration: a double-blind cross-over study of beclomethasone dipropionate aerosol spray. AB - A double-blind crossover study is described of the effect of beclomethasone dipropionate aerosol spray in patients with recurrent (minor) aphthous oral ulceration. Patients included in the study had normal haematological parameters of haemoglobin, ferritin, vitamin B12 and corrected whole blood folate. The design of the study incorporated a washout period and duration of effect was evaluated up to six months. Beclomethasone dipropionate significantly reduced ulcer pain severity and ulcer frequency, but had no significant effect on recurrence of oral ulceration. The preparation was associated with a high patient compliance and has benefit in relieving symptoms in patients with recurrent minor aphthous ulceration. PMID- 2587983 TI - Small bowel volvulus, mesenteric band, cavernous haemangioma, and failure to thrive. PMID- 2587984 TI - Beckwith-Wiedemann syndrome. PMID- 2587986 TI - Temperature and sperm incorporation in polyploid salamanders. AB - Although most animals reproduce sexually, a number of all-female groups exist. Triploid hybrid salamanders appear to maintain themselves by using a male's sperm to activate their eggs, after which the sperm nucleus is eliminated (gynogenesis). The incidence of sperm nuclear incorporation in eggs of these salamanders depends on temperature. Triploid offspring derived gynogenetically are more frequent at lower temperature, whereas tetraploid offspring derived sexually are far more frequent at higher temperatures. Temperature-dependent variability in sperm nuclear incorporation helps explain the variability in reproductive modes reported for hybrid salamanders. PMID- 2587985 TI - Purification, cloning, and expression of ciliary neurotrophic factor (CNTF). AB - Ciliary neurotrophic factor (CNTF) is one of a small number of proteins with neurotrophic activities distinct from nerve growth factor (NGF). CNTF has now been purified and cloned and the primary structure of CNTF from rabbit sciatic nerve has been determined. Biologically active CNTF has been transiently expressed from a rabbit complementary DNA clone. CNTF is a neural effector without significant sequence homologies to any previously reported protein. PMID- 2587987 TI - Failure of T cell receptor V beta negative selection in an athymic environment. AB - The mature T cell receptor (TCR) repertoire is the result of selection events during T cell development. Previous assessment of TCR beta-chain selection with serologic and molecular probes demonstrated both positive and negative selection. Although this work suggested a critical role for the thymus, no direct assessment has been made of the requirement for a thymus in TCR V beta selection. A comparison of TCR V beta expression in four different congenic pairs of normal and nu/nu (athymic) mice indicated that the normal V beta deletions associated with tolerance to self minor lymphocyte stimulating (Mlsc) antigens or to self major histocompatibility complex (MHC)-encoded E alpha E beta products did not occur in most athymic mice. Thus, the thymus has a critical role in mediating self tolerance by negative selection. PMID- 2587988 TI - Dispute surfaces over paternity of RU 486. PMID- 2587989 TI - The choosing of the NIH director. PMID- 2587990 TI - RU 486 development. PMID- 2587991 TI - UCLA and precollege science. PMID- 2587992 TI - Minor errors in two published sequences. PMID- 2587993 TI - Hard times at NIH. PMID- 2587994 TI - House trims off academic pork. PMID- 2587996 TI - Drug decriminalization. PMID- 2587995 TI - Soviet sociology makes a comeback. PMID- 2587997 TI - Budget fix hits research grants. PMID- 2587998 TI - Golden opportunities seen in biology. PMID- 2587999 TI - Science gives ivory a sense of identity. PMID- 2588001 TI - Human genome project: who will pay? PMID- 2588000 TI - 1,25-dihydroxyvitamin D-responsive element and glucocorticoid repression in the osteocalcin gene. AB - The active hormonal form of vitamin D3, 1,25-dihydroxyvitamin D3[1,25(OH), which regulates cellular replication and function in many tissues and has a role in bone and calcium homeostasis, acts through a hormone receptor homologous with other steroid and thyroid hormone receptors. A 1,25(OH)2D3-responsive element (VDRE), which is within the promoter for osteocalcin [a bone protein induced by 1,25(OH)2D3] is unresponsive to other steroid hormones, can function in a heterologous promoter, and contains a doubly palindromic DNA sequence (TTGGTGACTCACCGGGTGAAC; -513 to -493 bp), with nucleotide sequence homology to other hormone responsive elements. The potent glucocorticoid repression of 1,25(OH)2D3 induction and of basal activity of this promoter acts through a region between -196 and +34 bp, distinct from the VDRE. PMID- 2588003 TI - Panel to redesign NIH director's job. PMID- 2588002 TI - HIV, drugs, and ecology. PMID- 2588004 TI - Learning how to bottle the immune system. PMID- 2588005 TI - Spatial patterns from oscillating microtubules. AB - Microtubules are fibers of the cytoskeleton involved in the generation of cell shape and motility. They can be highly dynamic and are capable of temporal oscillations in their state of assembly. Solutions of tubulin (the subunit protein of microtubules) and guanosine triphosphate (GTP, the cofactor required for microtubule assembly and oscillations) can generate various dissipative structures. They include traveling waves of microtubule assembly and disassembly as well as polygonal networks. The results imply that cytoskeletal proteins can form dynamic spatial structures by themselves, even in the absence of cellular organizing centers. Thus the microtubule system could serve as a simple model for studying pattern formation by biomolecules in vitro. PMID- 2588006 TI - Cell cycle-dependent regulation of phosphorylation of the human retinoblastoma gene product. AB - The human retinoblastoma gene (RB1) encodes a protein (Rb) of 105 kilodaltons that can be phosphorylated. Analysis of Rb metabolism has shown that the protein has a half-life of more than 10 hours and is synthesized at all phases of the cell cycle. Newly synthesized Rb is not extensively phosphorylated (it is "underphosphorylated") in cells in the G0 and G1 phases but is phosphorylated at multiple sites at the G1/S boundary and in S phase. HL-60 cells that were induced to terminally differentiate by various chemicals lost their ability to phosphorylate newly synthesized Rb at multiple sites when cell growth was arrested. These findings suggest that underphosphorylated Rb may restrict cell proliferation. PMID- 2588008 TI - [Incidence and course of early local complications following surgery of the locomotor system (2)]. AB - In the department of traumatology, hand surgery, plastic and rehabilitation surgery of the University of Ulm, a prospective study was carried through over a period of 5 years (1980-1984) to record all early local complications; their course and final outcome were observed throughout this period. A total of 30,217 operations were performed, and we observed a total of 527 (i.e. 1.74%) perioperative and early postoperative complications in 447 patients. This rate remained nearly the same throughout the observation period. The complication most often found was postoperative hematoma, with an incidence of 0.61%; the hematoma had to be removed in a second operation in two-thirds of all cases. The next most frequent complication was infection of soft tissue and bones (incidence 0.49%), followed by lesions of nerve fibres (0.22%) and disturbances of wound healing and necrosis (0.15%). In comparison with those complications we were seldom confronted with luxations after implantation of femoral head prostheses, incorrect internal fixation, refractures and ischaemia after lesion of blood vessels. Most complications were localised in the knee (21.2%) and the lower leg (18.3%). We only observed 148 early complications (infection rate 0.49%), with 54 occurring in bones and joints and only 94 in soft tissue. In open fractures the infection rate totalled 2.03% and in closed fractures, 0.16%. We observed 14 joint infections (infection rate 0.16%), with 3 infections after the implantation of femoral head prostheses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588007 TI - An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. AB - Hematogenous metastasis requires the arrest and extravasation of blood-borne tumor cells, possibly involving direct adhesive interactions with vascular endothelium. Cytokine activation of cultured human endothelium increases adhesion of melanoma and carcinoma cell lines. An inducible 110-kD endothelial cell surface glycoprotein, designated INCAM-110, appears to mediate adhesion of melanoma cells. In addition, an inducible endothelial receptor for neutrophils, ELAM-1, supports the adhesion of a human colon carcinoma cell line. Thus, activation of vascular endothelium in vivo that results in increased expression of INCAM-110 and ELAM-1 may promote tumor cell adhesion and affect the incidence and distribution of metastases. PMID- 2588009 TI - [Treatment of 2d and 3d degree complicated tibial shaft fractures with the PMMA bead pouch technic]. AB - In a consecutive series of 222 compound fractures treated at the University of Louisville Level I Trauma Center from November 1984 to January 1987, 21 severe compound tibia shaft fractures in 20 patients were managed with the antibiotic bead pouch technique. There were 5 tibia shaft fractures and 16 tib-fib fractures. There were 9 type II and 12 type III (4 III A and 8 III B) open tibias. The patients' ages ranged from 16 to 50 years; the mean age was 29 years. There were 19 men and 1 woman. The Injury Severity Score (I.S.S.) ranged from 9 to 34; the mean I.S.S. was 14.4. Porous plastic film (Opsite) is placed over the soft tissue defect to establish a "closed" bead - hematoma - fracture environment containing high local levels of antibiotic at the fracture site. All patients had external skeletal fixation, serial wound debridement, and parenteral systemic antibiotics (cefazolin, penicillin, tobramycin). An aggregate of 46 bead pouch changes were performed in the 21 tibia fractures. During these changes, 86 cultures were taken, 5 of which were positive. One patient developed a wound infection, which was caused by tobramycin-resistant Pseudomonas and Enterococcus. No cases of osteomyelitis were observed at the fracture site. Wound closure was obtained in 9 fractures with delayed primary closure, and in 12 fractures with flap coverage and/or split thickness skin grafting. All patients underwent autogenous cancellous bone grafting after wound closure was established. The mean follow-up was 26 months (range 13-43 months). At final follow-up, 4 results were rated excellent, 11 good, 3 fair and 3 poor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588010 TI - [Treatment of open tibial fracture with fixateur externe]. AB - External fixation with a Hoffmann or an ASIF frame was used in the treatment of 50 severe open lower leg fractures from 1979 to 1987. In 7 cases consolidation was achieved by means of external fixation without changing to any other method. Plaster cast fixation was subsequently performed after soft-tissue healing in 35 patients. Further methods of treatment applied after external fixation were intramedullary nailing in 5 cases, internal stabilization with a plate in 1 case and provision of a surgical support in 1 case. In 1 patient early amputation was necessary. On average, fracture healing took 6.7 (4-15) months, significantly correlating with the severity of soft-tissue lesion. Compound fractures of the proximal tibial shaft turned out to be problem cases, requiring up to 15 months for bone union. Acute infections occurred in 6 cases (12%), despite primary antibiotic prophylaxis. Nonunion was noted in 2 patients. A follow-up examination of 33 patients after a median of 45 months (range 6-99) showed full weight bearing in all cases. Persistent soft-tissue problems were found in 7 patients, chronic osteitis in 4, and shortening of the extremity by up to 2 cm in 11 cases. One-third of the patients were out of work or had had to change their jobs as a social effect of their severe injuries. PMID- 2588011 TI - [Intractable pain of the Gerdy tuberculum. Lengthening of the iliotibial tract by Z-plasty. A case report]. AB - A painful disabling condition in the region lateral to the knee was recognized in a woman undergoing military physical training and sport activities; a review of the literature failed to yield a previous description of intractable pain at the Gerdy's tubercle. This disorder or syndrome is characterized by pain and tenderness over the Gerdy's tubercle and by aggravation of this pain on flexion and extension of the knee. Z-Lengthening of the iliotibial tract proximal to the Gerdy's tubercle has been found to relieve the symptoms after conservative measures (splinting, anti-inflammatory drugs and local steroid injection) have failed. The author suggests that this disorder may be traction syndromes. PMID- 2588012 TI - [Experimental study for clarification of the pathogenic mechanism in traumatic peroneal tendon dislocation]. AB - An experimental trial was performed to illustrate the causative mechanism of peroneal tendon luxation. It seemed that traumatic luxation of the peroneal tendons was found to originate in dorsiflexion, abduction and eversion of the forefoot. On the other hand, unless the peroneal muscles are at high tension and the ankle joint supported with a high shoe or similar a trimalleolar ankle fracture is likely. The depth of the retromalleolar groove is only one more factor predisposing to luxation of the peroneal tendons. PMID- 2588013 TI - Retinoids: new skin for the old. PMID- 2588014 TI - dsDNA--measurement by enzyme linked immunosorbent assay and clinical usefulness. PMID- 2588015 TI - The role of ESWL in the treatment of large kidney stones. AB - With extracorporeal shock wave lithotripsy firmly established as the treatment of choice for the majority of kidney stones, the management of large stone burdens and staghorn stones remains a point of discussion(1,2,3,4). Although with increasing experience the original limitations(5,6) posed by the size and the number of kidney stones have gradually become less important, most centres still approach large stones with a combination of percutaneous ultrasound lithotripsy and ESWL. This article reports on a personal series of 96 kidneys with an average stone burden of 51 mm treated by ESWL alone or in combination with indwelling ureteral drainage tubes, so called double J stents. Of these 96 kidneys, twelve were treated in one session, 74 in two, nine in three and one in four sessions. At six to twelve weeks after their last treatment session 42 were stonefree, 30 contained residual fragments smaller than 3 mm and four contained fragments larger than 3 mm. Complications were hematuria, pain, fever, encrustration of stone on the double J stent, spontaneous knotting of the double J stent and subcapsular hematoma. No kidneys were lost in this series and no deaths occurred. The results are comparable to those of combined PCN and ESWL(1). A case is made for ESWL with internal drainage by double J stent as the only auxiliary measure in kidneys with large stone burdens(7,8). PMID- 2588016 TI - The distribution of the ABO genotypes and phenotypes in Singapore in 1987. AB - The aims of this study are to determine for the 3 main ethnic groups in Singapore: a) the ABO phenotype distribution in 1987 b) the A, B and O gene frequencies c) the proportion of A and B group individuals who are homozygous using (i) temporal studies (trial & error) (ii) the derived A and B gene frequencies This paper presents the method of study and the results obtained using a sample of 39,019 blood donors in 1987. The opportunity has also been taken to compare the data derived in this study with that quoted in 2 previous studies. PMID- 2588017 TI - Subclavian catheters as temporary vascular access. AB - We reviewed our experience with subclavian vascular catheters (SVC) as temporary vascular access in the 18 month period 1 January 1984-30 June 1985. 37 consecutive patients using 49 vascular catheters received a total of 461 haemodialyses. Only 8 patients had acute renal failure. The rest were endstage renal failure (ESRF) patients awaiting definitive vascular access. Most of these latter patients were ambulant and were generally dialysed on an outpatient basis. 27 episodes of clinical septicaemia occurred and was the ONLY significant complication encountered. All but one patient responded to empiric therapy with cloxacillin +/- gentamicin and removal of the catheter. We conclude that SVC's are safe and suitable for use on an extended short-term basis especially in ESRF patients with vascular access problems. PMID- 2588018 TI - Chlamydial infection in female prostitutes in Singapore. AB - Three studies conducted in 1982, 1985 and 1988 investigated chlamydial infections in female prostitutes. In 1982, 115 prostitutes with culture-positive gonorrhoea were studied; 8% were coinfected with Chlamydia trachomatis. In 1985, 86 female prostitutes and in 1988, 100 female prostitutes attending for routine tests were examined. Chlamydia trachomatis was isolated in 12% and 9% of the cases, respectively. Gonorrhoea was detected in 10% and 11% of the cases. In the 1988 study, one (9%) of the 11 women with gonorrhoea had concomitant chlamydial infection. Syphilis was diagnosed in 3% of the female prostitutes investigated in 1988. Our findings indicate that concomitant chlamydial infection occurs in about 8-9% of female prostitutes with gonorrhoea and that 9-12% of the female prostitutes screened harboured Chlamydia trachomatis in their endocervices. A chlamydial control programme in prostitutes is desirable. PMID- 2588019 TI - Dermatological disorders resembling leprosy. AB - Three dermatological conditions - epidermolysis bullosa dystrophica (EBD), granuloma multiforme (GM) and mycosis fungoides (MF) were diagnosed elsewhere as leprosy either clinically or histologically. Although the morphology of the lesions were suspicious of leprosy there were few striking clinical findings which were unfavourable. Leprosy is still an important disease that should not be missed. However, the recognition of these skin disorders is highlighted so that unnecessary and prolonged treatment for leprosy can be avoided in endemic countries. PMID- 2588020 TI - The localizing value of downbeat nystagmus. AB - Downbeat nystagmus (DBN) is a primary position nystagmus with the fast phase in a downward direction. It is a rare but distinctive disorder of ocular motility and usually localizes the lesion at the posterior fossa. Four patients with DBN were seen in the department. One had a medullary glioma, and another congenital basilar invagination. The other two were initially diagnosed as demyelinating disease. One was subsequently found to have Arnold Chiari Malformation on magnetic resonance imaging (MRI). Review of the literature showed that cerebellar ectopia (Arnold Chiari Malformation) is the commonest cause of DBN. However 1/3 of reported cases have no obvious cause. DBN is of such high localizing value that we recommend MRI of cervicomedullary junction for all patients with DBN to exclude cerebellar ectopia or medullary lesion. PMID- 2588021 TI - Cotard's syndrome--two case reports. AB - Two cases of Cotard's Syndrome are described--one in a 33-year-old housewife suffering from paranoid schizophrenia and another in a 43-year-old housewife with acute psychotic depression. This rare syndrome is characterized by an extreme form of nihilistic delusion in which the patient, more frequently a woman, denies her own existence and that of the external world. Its onset is often sudden with no previous psychiatric history. Treatment of the condition depends on the underlying psychiatric illness. Both cases responded well to treatment. PMID- 2588022 TI - Cerebral tumours presenting with psychiatric symptoms. AB - Four cases of cerebral tumours presenting with psychiatric symptoms were referred to the psychiatrist for management. They displayed some degree of cognitive impairment, notably impaired memory for recent events, and nominal aphasia. Clinical neurological examinations were generally unremarkable with no evidence of focal signs or features of raised intracranial pressure. CT scan demonstrated parietal lobe lesions in all four patients with two showing involvement of the frontal lobe, one the temporal lobe and another the occipital lobe as well. Only one patient was operated, two died and the last continued treatment elsewhere. Factors contributing to the psychiatric symptomatology of cerebral tumours are raised intracranial pressure, location of the tumour, nature of the tumour and the individual constitution and response of the patient. PMID- 2588023 TI - Antenatal diagnosis of fetal abnormalities. AB - Fetal abnormalities may be strongly inherited e.g. in the Mendelian diseases. Some of the abnormalities are due to detectable chromosome anomalies, while the majority of fetal abnormalities arise as a result of the interaction of polygenes and environmental factors. The process of fetal abnormality diagnosis depends on a careful taking of the history and its evaluation. The clinical examination of the fetus by real time ultrasound, if relevant and finally special investigations which are to some extent invasive such as chorionic villus sampling, amniocentesis and fetal blood sampling. The fetal tissue so obtained may be assessed for their genetic structure by DNA recombinant methods, or the disease may be diagnosed by analysis of the genic products. The commoner hereditary diseases probing fetal abnormalities in S.E. Asia are described and the diagnosis of these diseases discussed. Fetal diagnosis, at the moment, is still labour intensive and costly and must be applied in a discriminate fashion. PMID- 2588024 TI - Noonan's syndrome with mental retardation presenting with an affective disorder- case report. AB - A 30 year old Chinese lady initially thought to have Turner's Syndrome was rediagnosed as Noonan's Syndrome following admission to a psychiatric hospital for treatment of an Affective Disorder (Hypomania). The genetics and morphological features in Noonan's Syndrome are briefly discussed and the patient's psychiatric presentation is described. PMID- 2588025 TI - Epitheloid sarcoma of the vulva. AB - A rare case of epitheloid sarcoma of the vulva is described. This is a soft tissue malignancy arising from tenosynovial tissue. The patient presented with a painless lump of the vulva of a month's duration. An excision biopsy was performed followed by a wide local excision after the actual diagnosis was confirmed. Post-operatively, her recovery was uneventful and she was seen in the Cancer clinic at regular intervals. Three years following surgery, she was well with no evidence of any recurrence. The suggested mode of treatment ranged from a wide local excision to radical vulvectomy with groin node dissection. PMID- 2588026 TI - Systemic amyloidosis with severe amyloid heart disease--a case report. AB - Cardiac Amyloidosis was first observed by Vichow in 1957. Since then many more cases have been documented, but there has been no case report of mortality from severe cardiac involvement in the local literature. We describe one such case seen in the Singapore General Hospital and review briefly the clinico pathological data on this uncommon entity. PMID- 2588027 TI - Aortic valve replacement in osteogenesis imperfecta tarda--a case report. AB - A case of osteogenesis imperfecta tarda presenting with infective endocarditis and heart failure is discussed. Urgent aortic valve replacement was performed but the patient succumbed from pneumonia. The rarity of this disorder and the special problems encountered surgically in these patients are briefly discussed. PMID- 2588028 TI - Computed tomography-osteoabsorptiometry for assessing the density distribution of subchondral bone as a measure of long-term mechanical adaptation in individual joints. AB - To estimate subchondral mineralisation patterns which represent the long-term loading history of individual joints, a method has been developed employing computed tomography (CT) which permits repeated examination of living joints. The method was tested on 5 knee, 3 sacroiliac, 3 ankle and 5 shoulder joints and then investigated with X-ray densitometry. A CT absorptiometric presentation and maps of the area distribution of the subchondral bone density areas were derived using an image analyser. Comparison of the results from both X-ray densitometry and CT absorptiometry revealed almost identical pictures of distribution of the subchondral bone density. The method may be used to examine subchondral mineralisation as a measure of the mechanical adaptability of joints in the living subject. PMID- 2588029 TI - Ulnar variance in children--standard measurements for evaluation of ulnar shortening in juvenile rheumatoid arthritis, hereditary multiple exostosis and other bone or joint disorders in childhood. AB - Measurements for radioulnar variance in adults cannot be used in children because the epiphyses are not fully ossified. We describe a method of determining ulnar variance in children by using the distance from the distal metaphysis of the radius to the distal metaphysis of the ulna. Standards for this measurement are presented for ages 1.5 to 15.5 years in boys and girls. These measurements change little with age and may be helpful in establishing shortening of the ulna which may been seen in juvenile rheumatoid arthritis, hereditary multiple exostosis, or other bone and joint diseases with childhood onset. PMID- 2588031 TI - Disc degeneration in Scheuermann disease. AB - Comparison of the radiographic signs of Scheuermann disease and the corresponding disc degeneration on thoracolumbar magnetic resonance (MR) images was made in 21 young patients. Marginal sclerosis, Schmorl nodes and narrowed disc spaces, but not irregular or wedge-shaped end-plates, were significantly associated with disc degeneration. Fifty-five percent of the discs in the patients with Scheuermann disease were abnormal on MRI, compared with 10% in asymptomatic controls. Our study confirms that thoracolumbar disc degeneration is enhanced in 20-year-old patients with low back pain who have radiological evidence of Scheuermann disease. PMID- 2588030 TI - Osteodensitometry of vertebral metastases after radiotherapy using quantitative computed tomography. AB - Bone density has been assessed during and after radiotherapy of metastases of the spine using quantitative computed tomography (QCT) in 19 patients with osteolytic vertebral lesions. All patients underwent external photon radiation with a total dose of 40 Gy over a period of 4 weeks. Measurements of vertebral mineral density were performed at the beginning, at the end, and 3 months after radiotherapy. In 13 patients with osteolytic metastases, radiotherapy achieved complete release of pain; it was unsuccessful in the remaining 6 patients. Immediately after successful radiotherapy, osteolytic metastases showed a decrease of bone density of 24.7% followed by an increase of 60.6% 3 months later. Normal bone surrounding the osteolysis showed an increase of density at the end and 3 months after radiotherapy. QCT has proved to be a helpful tool in assessing successful radiotherapy of metastases of the spine. PMID- 2588032 TI - Magnetic resonance demonstration of hyperintense herniated discs and extruded disc fragments. AB - Magnetic resonance (MR) imaging is useful in evaluating a variety of spinal pathologies including intervertebral disc disease. Herniated discs are commonly believed to undergo premature degeneration and produce low intensity signal on T2 weighted images. We reviewed 154 patients who were studied for disc herniations or other pathology. Fifty-nine (38%) had disc herniations and 7 of these (5%) had a fragment that was hyperintense with respect to the adjacent intervertebral disc on T2-weighted images. It is hypothesized that some disc fragments may contain a higher water content that causes prolongation of the T2 signal. The bright signal which is therefore seen on long TR long TE (T2-weighted) images may be a useful sign suggesting herniation or extrusion. PMID- 2588033 TI - Micromelic bone dysplasia with cloverleaf skull. PMID- 2588034 TI - Case report. Diffuse cortical destruction in both femurs and the left humerus in puerperium. PMID- 2588035 TI - Case report 572. Osteosclerotic myeloma (POEMS) syndrome. PMID- 2588036 TI - Case report 573. Aneurysmal bone cyst of acetabulum. PMID- 2588037 TI - Case report 574. Periosteal osteoblastoma of rib. PMID- 2588038 TI - Case report 575. Infantile myofibromatosis. PMID- 2588039 TI - Case report 576. Anaplastic sacrococcygeal chordoma (dedifferentiated chordoma). PMID- 2588041 TI - Case report 578. Painful, enlarging mass on the inner aspect of the left upper arm. PMID- 2588040 TI - Case report 577. Metastatic paraganglioma. PMID- 2588042 TI - Hidden consequences of state violence: spinal cord injuries in Soweto, South Africa. AB - Many spinal cord injured people in Soweto are victims of direct, repressive state violence, such as police shootings. All of them are victims of the indirect structural violence that is institutionalized against both blacks and disabled people in South Africa. SCI people in Soweto are therefore subject to two sources of disadvantage and exclusion. This paper describes a survey of 88 SCI Sowetans. Their lives are marked by poverty and social isolation. Their experiences bring into sharp focus some of the concrete and hidden results of apartheid as a violent and disabling system. PMID- 2588043 TI - Issues of definitions and their implications: AIDS and leprosy. AB - It is demonstrated how definitions can determine social consequences of impairment and disability. A comparison between leprosy and AIDS provides the basis for the discussion. The United States is the geographic and political arena under consideration. Issues of classification as STD (sexually transmitted disease) or as contagious, communicable disease are relevant. An important factor to predict the social impact is the nomenclature utilized by CDC (Center for Disease Control). CDC represents the government as the official agency to gather and report morbidity and mortality information. Hypotheses to explain stigma on the basis of epidemiological bases are added to the usual sociological concepts or historical considerations. Potential application of the findings are discussed. PMID- 2588044 TI - Low utilization of community health workers: results from a household interview survey in Burkina Faso. AB - A representative household survey was carried out in order to study the utilization of community health workers (CHW) in relation to other sources of health care. We found three main results: (1) For mild diseases, villagers consulted their CHW only in 8.8% of mild diseases, in 69% the family remained the main provider of primary care. (2) In the case of serious diseases, which the CHW was supposed to identify and refer, the villagers bypassed the CHW in 96.5%. The professional health worker were consulted directly in the majority of serious disease. (3) Sick infants were not taken to the CHW for treatment. (4) No pattern of referral between professional and CHWs could be traced. Severity of disease and perceived effectiveness of the treatment were the most important determinants of health seeking behavior. Availability, distance, and cost of travel and drugs were important service related determinants. Individual and household characteristics such as income, ethnicity, and household size were only weakly associated with choice of curative care. Reasons for the low utilization of CHWs are outlined and policy implications discussed. PMID- 2588045 TI - Power and pain: the location of pain and fear in dentistry and the creation of a dental subject. AB - It has been argued that the meaning of pain in childbirth and in general medicine has changed and that this change was part of a cognitive transformation that occurred in medicine during the post World War II period. This paper uses Foucault's notion of the gaze and his unique conception of power to explore the extent to which the understanding of pain, and the associated concept of fear, in dentistry, reflects those understandings found in medicine and obstetrics. Within the discourse of dentistry the conception of pain is both object and effect of the profession's techniques of observation and analysis. Analyses of pain and fear occurred on two levels: the micro-level of the individual and the macro level of the population. The examples of the case history and the epidemiological survey are used to demonstrate these two levels of power/knowledge. The first technique contributed to the constitution of the psychological space, the second technique confirmed the social space. Within these spatialisations new conceptualisations of pain were realised and a subjective dental subject was manufactured. The findings of this paper add weight to the thesis that the functioning of power/knowledge transcends professional and disciplinary boundaries and is a process which is far more subtle and fundamental than one of political manoeuverings by interested groups or individuals or the accumulation of an increasingly sophisticated knowledge. PMID- 2588046 TI - Private troubles and public issues: providing abortion amid competing definitions. AB - Sixteen years after the Supreme Court liberalized abortion policy, the United States continues to debate two competing and seemingly irreconcileable definitions of abortion. The experience of those who provide abortion has received relatively little research attention despite this unique set of historical circumstances. This paper presents findings from an exploratory study of 130 abortion workers (physicians, nurses and counselors). The data suggest that, despite formal beliefs about abortion rights, the situated experience of providing legal abortion evokes a range of abortion definitions. Seven central definition themes were cited repeatedly by the respondents: abortion as a woman's right, a destructive act, part of the practitioner's work, a technical procedure, a positive act, murder and an irresponsible act. Respondents perceived each definition to fit within one of three fixed and familiar perspectives: medical, pro-choice or pro-life. Each perspective was understood to have its own exclusive meanings, vocabulary and imagery which automatically remanded the situated definitions to a broader social context. Each definition of abortion was seen to define the event itself as well as to input specific meaning and differential value to what is aborted, the woman terminating her pregnancy, the nature of abortion work and the role of the practitioner. These definition components were perceived to be specific, codified and mutually exclusive within the different definition themes. They also were found to be linked to expected and specified feelings. The co-existence of feelings or definitions that were perceived as consistent was hardly noted by respondents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588047 TI - User fees for health care in developing countries: a case study of Bangladesh. AB - In designing country health care programs to achieve the goals of the Alma Alta declaration of 'Health for All', developing countries have been confronted with the problem of increased health care needs and decreased available resources. Health economists have proferred several possible solutions to this fiscal shortfall, including cost-recovery measures through the imposition of user fees for curative services at government health facilities. Health care providers have been noticeably absent from discussions of the many possible implications of these fees; consequently, resultant programs and policies may be economically sound but may fail to place a sufficient emphasis on features designed to maintain and improve the health of the population. In the present paper we examine the possible impact of user fees on the health of individuals residing in Bangladesh, one potential candidate country for user fees. We note evidence that the existing government health care system appears already to be providing care to two of the most medically vulnerable groups in Bangladesh, the poor and women, and provide evidence that such fees may seriously interfere with maintaining this patient profile. We discuss the significant public health role that curative care provides for the individuals, their families and the wider community. We suggest that additional questions should be asked by health care providers, anthropologists and economists prior to institution of user fees in the government system and that such measures should first be introduced in an experimental format with a rigorous and comprehensive impact evaluation. PMID- 2588048 TI - Swedish physicians' perspectives on work and the medical care system--V. Comparisons across specialties. AB - Treating medical specialties as segments, Swedish ambulatory care physicians were interviewed to identify their perspectives on work and the medical care system. Those perspectives were analyzed and compared across segments. Physician segments differed substantially in the themes they put forward. Perspectives tended to be homogeneous within segments and sharply differentiated between segments. Both positive and negative perspectives were expressed more with respect to immediate work situations than with respect to the medical care system. Child health and maternal health physicians were more likely to express satisfactions with both work and the system, while district general practitioners were more likely to note problems. It is contended that this study has identified well grounded (valid) categories for the analysis of the Swedish medical care system. PMID- 2588049 TI - A skin test survey of valley fever in Tijuana, Mexico. AB - Results of a study of the prevalence of valley fever among 1128 residents of Tijuana, Baja California are presented. Children from primary and middle schools (n = 497) and adults from technical institutes and maquiladoras (assembly plants) were tested for reaction to both spherulin and coccidioidin during 1985-1986, and they completed a questionnaire containing 23 variables on their socio environment. Place of residence was mapped. The population sampled is largely middle class. Discriminant analysis indicates the distribution of positive cases is not clustered, nor can it be correlated with geomorphic factors such as mesa tops, canyons, or valley bottoms. PMID- 2588050 TI - 'AIDS in Africa: emerging trends'. PMID- 2588051 TI - Complications of cervical spine surgery. A five-year report on a survey of the membership of the Cervical Spine Research Society by the Morbidity and Mortality Committee. PMID- 2588052 TI - Esophageal perforation following anterior cervical spine surgery. AB - The authors surveyed the Cervical Spine Research Society to compile a series of esophageal perforations following anterior cervical spine surgery. Twenty-two cases were assembled. Six occurred at the time of surgery, 6 in the postoperative period, and 10 weeks to months later. Eight surgeries were because of fracture. Hardware was implicated in 25% of cases occurring after surgery. Diagnosis was confirmed most often by direct vision at reexploration or esophography. Treatment usually consisted of drainage, repair, and parenteral antibiotics; 2 cases were successfully treated by enteral feeding and antibiotics alone. There was one fatality, and all patients required prolonged hospitalization. Cervical fracture and the use of hardware may be associated with this complication. Clinical suspicion and esophography are important diagnostic tools. Drainage and parenteral antibiotics are recommended treatment. PMID- 2588053 TI - Functional evaluation of the spinal cord by magnetic resonance imaging in patients with rheumatoid arthritis and instability of upper cervical spine. AB - Thirty-four patients with atlanto-axial instability due to rheumatoid arthritis were examined with plain x-ray views and functional magnetic resonance imaging (MR), and were neurologically evaluated. Transcranial brain stimulation was performed in 25 patients. In 22 cases, the authors observed inflammatory tissue thicker than 3 mm behind the odontoid peg. The spinal canal diameter was significantly decreased in the flexed position. Nine patients showed signs of cranial migration of the axis. The diameter of the spinal cord was measured to be 7.4 mm in the neutral position, and 6.5 mm in flexion. The difference between the diameter of the neutral and flexed positions was highly significant. Twelve of the 34 patients displayed clinical signs of cervical myelopathy, and 13 showed a significant delay of central motor latency, as calculated from the motor evoked potentials. Surgical intervention, either by a posterior approach only or combined with a transoral dens and inflammatory tissue resection, is recommended in patients with progressive atlanto-axial instability, pathologic clinical and neurophysiologic findings, and a spinal cord diameter of less than 6 mm in flexion. Severe pain and cranial migration of the axis, as measured by the MRI, also justify a surgical intervention. PMID- 2588054 TI - Fractures of the odontoid process. Treatment with anterior screw fixation. AB - Seventeen cases of Anderson and D'Alonzo Type II and "shallow" Type III fractures of the odontoid, treated by anterior screw fixation, were reviewed and compared with previously published series of fractures treated nonoperatively, treated with posterior C1-C2 arthrodeses, and with anterior screw fixation series. Although the nonunion rate (12%) and major complication rate (24%) in the present series were higher than those previously reported, the combined rates of all anterior screw fixation series were comparable to those of posterior C1-C2 arthrodesis studies. Three of the complications presented occurred in cases that in retrospect were inappropriate for the use of this technique. These included a verified nonunion and 2 individuals with markedly osteoporotic bone and unfavorable fracture type. Because of the difficulty involved in mastering anterior screw fixation of the dens, its use should be limited to experienced spine surgeons with the appropriate surgical facilities. PMID- 2588055 TI - Metastatic lesions of the upper cervical spine. AB - Metastatic lesions of C1 and C2 most frequently present with severe pain and only rarely with neurologic involvement. The lesions are poorly visualized on plain roentgenogram and most often require bone scan and/or computed axial tomography (CAT) scan for definitive diagnosis. Delay in diagnosis in frequent in these patients (8 of 16). Radiation therapy and external mobilization yield satisfactory results for minor fractures or diffuse involvement without instability. Surgery is rarely indicated for decompression. However, in patients with C1 lateral mass involvement or severe C2 body destruction with instability, posterior stabilization gives excellent relief of pain. Onset after diagnosis of the primary tumor ranges from months to years. Survival is reasonable (mean, 9 months) after diagnosis of upper cervical spine involvement. Understanding these characteristics and the occurrence of metastatic disease in the upper cervical spine allows earlier diagnosis with appropriate radiographic studies and prompt palliation of symptoms. PMID- 2588056 TI - Motor evoked potential monitoring during upper cervical spine surgery. AB - Motor evoked potential (MEP) produced by transcranial electrical stimulation was recorded from an epidural electrode in 20 consecutive patients during upper cervical spine surgery. In 5 patients, transient attenuation to approximately 50% followed by complete recovery was observed, and no neurologic deficit was noted. One patient had complete loss of MEP and was left a respiratory quadriplegic. In 2 cases, MEP amplitudes increased after tumor extirpation and remarkable remissions were observed. The MEP correlated with clinical outcomes and was a useful monitoring technique for upper cervical spine surgery, free of complication. In cat experiments designed to analyze conducting pathways, the maximal amplitude of the initial spike of MEP existed in the ventromedial spinal cord, which contains the extrapyramidal tracts. Motor evoked potential was proven to reflect motor function based on the spinal cord compression study. PMID- 2588057 TI - Acute ascending myelopathy of the spine. AB - Ascending myelopathy of the cervical spine is a clinical condition in which ascending paralysis manifests itself from 24 hours to 4 weeks after the initial injury. One hundred thirty-four patients with spinal cord injury were reviewed; 80 underwent surgery and 54 were treated conservatively. Ten of the 54 patients who did not have surgery ascended one to four levels, whereas only 4 of the 80 patients who underwent surgery ascended to similar levels. Myelography demonstrated diffuse swelling of the cord that extended approximately two segments above and below the injured vertebrae. Magnetic resonance imaging showed intrathecal hemorrhage within the first 2 weeks followed by cord atrophy within 4 weeks after the initial trauma. Thorough decompression of the cord with rigid internal fixation markedly reduced the incidence of this complication. PMID- 2588058 TI - Magnetic resonance imaging of acute cervical spine trauma. Correlation with severity of neurologic injury. AB - Prior to the advent of computer-assisted imaging techniques, conventional radiographic studies did not accurately depict the severity of soft tissue injury (spinal cord and paravertebral tissue) attending severe spinal trauma. Computed tomography scanning is clearly superior to plain radiography in the demonstration of osseous fractures and impactions, but this modality does not clearly depict ligamentous or disc injuries and does not image the spinal cord directly. The authors' preliminary experience indicates that magnetic resonance imaging (MRI) more accurately defines the extent of soft tissue damage in the zone of injury. In this study, the authors correlate these objective imaging techniques with findings on neurologic exam. Seventy-eight patients with cervical spine injuries admitted to the Regional Spinal Cord Injury Center of the Delaware Valley between August 1987 and January 1989 were evaluated with surface-coil MRI on a 1.5-Tesla unit. Fifty-nine patients were studied within 7 days of injury. Image sequences consisting of T1-, proton density, and T2-weighted images were obtained in saggital views. Axial gradient recalled acquisitions in the steady state (GRASS) images were obtained from most patients. We learned that certain patterns of MRI signal were associated with severe neurologic deficit. These include: 1) intramedullary hematoma and 2) spinal cord contusion associated with edema encompassing more than one spinal segment. Magnetic resonance imaging findings also correlated with less severe injury and include 1) normal spinal cord signal and 2) small focal contusions associated with edema encompassing one spinal segment or less. PMID- 2588059 TI - Clinical considerations and biochemical basis of prognosis of cervical spinal cord injury. AB - A total of 118 patients with cervical spinal cord injury were studied to determine the neurologic improvement achieved by either conservative or surgical treatment. Useful recovery was observed in 55% of the patients with incomplete cord injuries, but in none of those with complete cord injuries. There was no significant difference between the treatment groups regarding neurologic improvement. In experimental studies on rats, the increased levels of lipid peroxides and thromboxane after spinal cord injury were found to be proportional to the magnitude of injury. These evidences suggest that spinal cord injury is directly related with the magnitude of injury, and the prognosis is determined entirely at the time of injury. PMID- 2588061 TI - Multidirectional instabilities of traumatic cervical spine injuries in a porcine model. AB - Spinal injuries due to high-speed trauma are significant problems. The method of treatment depends on the stability determination of the injured spine. Young pig spines were injured at high speed to produce clinically relevant fractures and dislocations. The injuries were produced by dropping a mass onto the superior vertebra and causing three major types of trauma: flexion-compression, extension compression, and pure compression. The multidirectional instability of each spine was measured before and after trauma by applying pure moments to the three vertebrae segments. Lateral radiographs were taken of each intact and injured spine. Flexion trauma produced the greatest instabilities in flexion and extension, while extension trauma produced the greatest instabilities in axial rotation and lateral bending. Lateral radiographs were found to be inaccurate predictors of spinal instability. PMID- 2588060 TI - Dynamic response of human cervical spine ligaments. AB - This study was undertaken to investigate the dynamic response of human cervical spine ligaments. Uniaxial tensile failure tests were conducted on anterior longitudinal ligament (AL) and ligamentum flavum (LF) structures. These ligaments were tested under in situ conditions by transecting all the elements except the one (AL or LF) under study. A fixture was designed to properly align the specimen to induce a uniaxial mode of loading. A six-axis load cell was placed at the distal end of the specimen. The proximal end of the specimen was attached to the piston of a specially designed electrohydraulic testing device. The biomechanical properties of the ligaments were determined at four different loading rates of 8.89, 25.0, 250.0 and 2500 mm/sec. The mechanical response indicated nonlinear and sigmoidal characteristics. The ultimate tensile failure load, stiffness, and energy-absorbing capacity at failure were found to increase with increasing loading rates for both the AL and LF. However, the distractions at failure did not indicate this tendency. While the ultimate tensile force and ultimate energy absorbing capacity varied nonlinearly with the logarithm of the loading rate, the stiffness varied linearly. PMID- 2588062 TI - Kinematics of the cervical spine following discectomy and stabilization. AB - The immediate biomechanical stability of the cervical spine following discectomy and stabilization is described. Fresh human ligamentous spines (C2-T2) were potted, and clinically relevant loads were applied by a loading frame attached to the C2 vertebra of each specimen. A set of three infrared light-emitting diodes (LEDs) were attached rigidly to each of four vertebrae (C4 to C7) to record their spatial locations after each load step application using a Selspot II (Selcom Selective Electronic, Inc., Valdese, North Carolina) system. The specimen was tested in the intact state, following discectomy at the C5-6 intervertebral level, following insertion of a bone graft in the intervertebral space, and following the application of an anterior metal plate. The load-deformation data of the injured and stabilized tests were normalized with regard to the corresponding results of the intact specimens. At the injured level (C5-6), the load-deformation results indicated a highly significant increase in motion in flexion (66.6%), extension (69.5%), lateral bending (41.3%), and axial rotation (37.9%). After the insertion of the bone graft, a significant decrease in motion was seen in the effected segment in extension (-45.9%), with similar reductions in lateral bending and axial rotation and a smaller reduction in flexion. The application of an anterior metal plate in addition to the bone graft at the injured level provided significant reduction in motion (-70%) in all load modalities. This data may have clinical relevance regarding the role of internal fixation in cases of severe spine instability. PMID- 2588063 TI - Biomechanical evaluation of cervical spinal stabilization methods in a human cadaveric model. AB - The authors have previously reported in vitro testing of various posterior and anterior constructs (sublaminar, Rogers', and Bohlman's triple-wire wiring; AO hook plate fixation; and Caspar anterior plate fixation) in a bovine model with multiaxial biomechanical testing. This study was undertaken to evaluate the above constructs and other constructs in human cadaveric spines. Six subaxial human cervical spine specimens were biomechanically tested at the C5-C6 motion segment both intact and with a simulated distractive-flexion Stage 3 injury created at the C5-C6 level with complete disruption of the supraspinous ligament, interspinous ligament, ligamentum flavum, posterior longitudinal ligament, and facet joint capsules; with sufficient disruption of the intervertebral disc to allow a bilateral C5-C6 facet dislocation. The specimens were tested with a six channel Bionix MTS 858 materials tester (M.T.S., Minneapolis, Minnesota) using cyclic loads to simulate cervical compression, flexion, extension, and rotation with measurements of axial load, axial displacement, torque, rotation, and anterior and posterior strains. Eight constructs were tested nondestructively: the intact spinal segment, sublaminar wiring, Rogers' wiring, Bohlman's wiring method (triple-wire technique), Roy-Camille posterior plate fixation, AO posterior hook-plate fixation, Caspar anterior plate fixation, and AO posterior hook-plate with Caspar anterior plate fixation. There was no significant difference in flexural stiffness and torsional stiffness between any of the constructs tested; however, there was a significant (P less than 0.05) increase in the posterior strain during flexion and axial loading tests between the Caspar plate construct and all other tested constructs, including the combined posterior and anterior plating construct. These differences persisted after cyclic testing of 100 cycles. Biomechanical testing demonstrated no significant differences between any of the posterior stabilization methods tested. Caspar anterior plating is clearly an inferior method of treating distractive flexion injuries of the cervical spine when compared with all posterior fixation techniques. Also, there is little biomechanical justification for the use of potentially dangerous sublaminar wire fixation and posterior plating methods in these injuries (with intact bony posterior elements), since the relatively safe interspinous wiring methods (Rogers' and Bohlman) are just as rigid as these other posterior fixation techniques. PMID- 2588064 TI - [Trauma and poisoning as causes of the demand for emergency services]. AB - A retrospective survey of injuries that were treated during 1985-1986 in the emergency rooms of the four general hospitals managed by the Departamento del Distrito Federal was carried out. Data were classified by month, day of the week, shift, degree of alcohol intake, type of injury (according to the 9th revision of the International Disease Classification), age-group, sex, cause of the injury (accident or violence), and the area to where the patients were channeled after leaving the emergency room. The most affected age groups were 15-19 and 20-24 years. Males accounted for 70% of the cases. In this study we present information that will prove valuable for the planning, control, and evaluation of emergency care programs in hospitals specialized in injuries. PMID- 2588065 TI - [Effectiveness of seat belts in automobiles]. AB - Studies in other countries have demonstrated that properly worn seatbelts dramatically reduce the likelihood and seriousness of injuries in motor vehicle accidents. However, in the western region of Mexico, they are very rarely worn, due to the erroneous belief that its use does not protect, and may even harm its wearer. In order to ascertain its benefit or lack of it, we undertook a survey, comparing the degree of severity of lesions sustained, as well as the mortality, between a group of 15 patients who wore seatbelts and another of 35 patients who did not wear them; all patients were treated at the Emergency Room of the Hospital de Especialidades del Centro Medico de Occidente, after suffering car accidents. Among the first group, only one patient required hospitalization and there were no deaths. In the second group, all 35 patients had to be hospitalized, eight had sequelae and nine died. We conclude that seatbelts effectively protect the wearer against death and limit the severity of the injuries suffered during car accidents. We propose that educational campaigns to convince the public as to the benefits of its use should be carried out, and after a reasonable interval its use should be mandated by law. PMID- 2588066 TI - [Strategy for controlling poliomyelitis in Mexico: greater vaccination coverage of children less than 1 year of age]. AB - In spite of the widespread use of oral poliovirus vaccine, some countries have not achieved an optimal control of poliomyelitis. According to Sabin, this fact is due to a lack of immunization coverage of children under one year of age. In this study, the relationship between the general morbidity rate for polio and vaccination coverage of children under one year of age, in people protected by the Mexican Institute of Social Security, is analyzed. There is a negative correlation between these two variables: the lesser the coverage, the greater the rates. There is also a correlation between the rate of polio and the rate of polio for the year prior to each of the years of the study period. In a multiple regression model, both the coverage and the rate for the previous year were significantly correlated with the rate of polio. In order to get an optimum control of this disease, it is advantageous to consider that it is not enough to increase the coverage but that this coverage must be opportune, i.e., in the first year of life. PMID- 2588067 TI - [Evaluation of a program for monitoring of nosocomial infections]. AB - The results of two nosocomial infection surveillance programs are presented. They were conducted sequentially during a period of eight months, in a general hospital in Mexico City. The purpose of the study was to evaluate the results of a previously installed program based on the investigation of the incidence of episodes of nosocomial infections through the results of the investigation of the prevalence of these episodes. The observed prevalence and incidence rates and the calculated incidence rate were 23 percent, (127 episodes in 547 patients); 4.52 percent (134 episodes in 2,963 discharges) and 4 percent. The commonest problems detected by both studies were surgical wound and urinary tract infections. Pseudomonas and coagulase negative Staphylococcus were isolated most frequently during each period. It is concluded the system based on the investigation of the incidence of nosocomial infections works adequately in this hospital. The advantages of the design of the prevalence system are discussed, since it permitted the analysis of the infection risk associated to different invasive procedures. The odds ratio for acquiring respiratory infection was 152 (C.I. 95%: 31,732) in patients that underwent tracheostomy, 20 (C.I. 95%: 4 90) in patients with respirator, 34 (C.I. 95%: 8,142) in patients with endotracheal tube and 33 (C.I. 95%: 8,137) in patients with nasogastric tubes. PMID- 2588068 TI - [Epidemiologic monitoring and decentralized planification: the use of sentinel sites in Guerrero]. AB - With the current decentralization of health care in the Mexican state of Guerrero, there is need for detailed but inexpensive information for the planning of health services. A cyclical process of measurement is proposed using sentinel sites, characterized as places of concentration of measurement resources, which are not special intervention areas or health facilities. The sites in Guerrero were selected to be representative of the health conditions in the state. During the first two years, study cycles were carried out regarding acute respiratory infections and diarrhoeas in infants, the risk factors associated with these afflictions and the attention paid to them within the community. Later cycles focussed on the importance of scorpion stings and Chagas' disease, the impact of measles vaccination and the prevalence of tuberculosis. Three types of community based data are considered in each cycle, to optimize their use in planning (impact, coverage and costs) which, in summary formats, facilitate rapid analysis and presentation. PMID- 2588069 TI - [The prevalence of chronic drinkers in Mexico: an ecologic analysis]. AB - Alcohol consumption is an important element in the epidemiologic profile of Mexico. This can be confirmed observing the increased per capita consumption of certain alcoholic beverages (like beer and wine), alcohol related medical problems (e.g. liver cirrhosis), social problems (i.e. violence) and by the data provided by household surveys of prevalence of alcohol consumption in Mexico since the 60's. The population's consumption of alcoholic beverages has generated concern, as the Simple Distribution Theory (SDT) predicts that an increment in the per capita alcohol consumption is likely to be accompanied by an increment of heavy drinkers. This increment is, then, related to a theoretical increment in alcohol related damages. In order to partially test the SDT data from a series of surveys done in the country, six surveys of the 70's were used. Those surveys were executed in six cities, the capital of five states and the capital of the Republic, with a comparable methodology and definition of alcohol consumption. We used prevalence data of heavy drinkers in those cities as an independent variable for a series of medical and social problems, in a multiple-group comparison study. In general, the results do not support the SDT in the case of mortality by liver cirrhosis, suicide and traffic deaths, or for alcohol related offenses at the Federal Courts. Nevertheless, the results seem to support the SDT for some groups in Common Court offenses and for the rate of traffic accidents. In a comparison with other independent variables (prevalence of abstainers, per capita bars, illiteracy, unemployment, and population density), the prevalence of heavy drinkers and population density were the best. Both obtained the largest number of statistically significant correlations with the problems studied. For the prevalence of heavy drinkers some of those correlations were in the inverse sense as predicted by the SDT. PMID- 2588070 TI - [The modified psychiatric interview: a study of reliability]. AB - In order to estimate the prevalence of mental disorders in epidemiologic studies in the community, our department has designed the Modified Psychiatric Interview (MPI), a semi-structured interview derived from the Standardized Psychiatric Interview by Goldberg et al. This instrument confirms the presence of "psychiatric cases" and is applied by interviewers with clinical experience. The purpose of this article is to evaluate the degree of agreement between clinical interviewers (using an interviewer-observer design), utilizing MPI in an out patient population attending a general hospital, as part of an investigation on prevalence of mental disorders at a 2nd. level of medical care. The degree of agreement was calculated in the different sections of the instrument by Pearson's product-moment correlation, Kappa statistic and Yule's "Y" coefficient. The results showed a high level of reliability among the clinical interviewers in each section of the MPI. PMID- 2588071 TI - [Education for dental health in pregnancy]. AB - In health education it is important to emphasize knowledge about oral hygienic techniques in order to decrease the morbidity due to caries and periodontal disease. The Dental Office of the National Institute of Perinatology has developed educational activities with patients during the last ten years. With this experience, we have created an educational program concerning hygienic techniques designed to prevent the commonest oral diseases. We undertook an investigation to evaluate the results of this educational program. Experimental and control groups were subjected to a program including a 90 minute conference, a booklet and a video about caries, periodontal disease and oral hygienic techniques. The experimental group also had six practical sessions related to teeth brushing and dental thread usage. We evaluated the knowledge and the oral hygienic techniques. The results show an initial increase in knowledge in both groups; however, a later evaluation showed a decrease towards the original level. The difference in the group with practical training was evident. We agree with other authors on the necessity of a continuous education program. PMID- 2588072 TI - [Massive use of coproparasitoscopy with a phenol-alcohol-formaldehyde fixing solution]. AB - The use of a fixing solution (FAF) to preserve parasite specimens in routine coproparasitoscopy is considered in this paper as an essential tool in surveys and field work aimed at diagnosing intestinal parasitic disease. It increases the reliability of the analysis procedure when the samples have to be transported over long distances to a central laboratory. PMID- 2588073 TI - [Gnathostomiasis in Mexico]. AB - Since 1975, increasing numbers of patients with inflammatory, migrant, recidivant nodules were observed in the towns of Temazcal, state of Oaxaca, Tierra Blanca, Veracruz and others along the Papaloapan river. Larvae of Gnathostoma sp. have been obtained from some of them. The local species, although not completely identified, must be very close to G. spinigerum. Infection is related to ingestion of "ceviche", a very popular mexican delicacy made with raw Cyclid fishes of the Miguel Aleman dam. Ecological and social changes provoked by the construction of the dam and hypotheticaly related to the dissemination of the parasite are described. As the Temazcal Fish Culture Center has delivered tilapia fishes to many secondary culture centers, it is feared that the infection could spread through the country, so signs and symptoms of the disease are described in order to help Mexican doctors make the diagnosis if they were to encounter the disease. PMID- 2588074 TI - [Advances in public health investigation. 5 years' work of the Center for Research in Public Health, 1984-1989]. AB - Five years after the creation of the Center for Public Health Research (SPHR), this essay reviews its origins and evolution and points to the challenges it will face in the future. The seven basic organizational principles underlying the academic development of the Center are described. In the quantitative aspect, the institution's growth is reflected in the rapidly increasing trend in the number of researchers, projects and scientific publications, as well as in the volume of the external financial resources received. In the qualitative aspect, the article highlights the ever growing number of themes approached by the seven lines of research, the elaboration of conceptual models, the creation of data bases and the methodological development. Among the most important challenges of the CPHR in the future are: (1) solving existing organizational problems; (2) building links with the decision makers and (3) establishing an equilibrium between relevance and excellence in public health research. PMID- 2588075 TI - [Towards an integrated approach of research and education in public health]. AB - In this brief essay the steps to construct a model that can integrate research and higher education in the service of public health are discussed. First, the author presents the problem in general terms, and then the specific applications are described. PMID- 2588076 TI - [A comparative study of computed tomographic and surgical findings in cervical and lumbar disk herniation. A comparative study of computed tomography and surgery]. PMID- 2588077 TI - [Dilatation of the azygos vein in agenesis of the inferior vena cava]. PMID- 2588079 TI - Are we training too many surgeons? PMID- 2588078 TI - Nursing in the RSA--a perspective. PMID- 2588080 TI - Permanently disabled? PMID- 2588081 TI - Plasma lactoferrin content in pregnancy. AB - Plasma lactoferrin concentration, leucocyte count, serum prolactin concentration and storage iron status were studied in 313 women at various stages of pregnancy. The mean serum iron value, percentage saturation of transferrin and geometric mean serum ferritin concentrations decreased as pregnancy progressed. In contrast, the total iron-binding capacity showed a highly significant increase with advancing gestation. Plasma lactoferrin concentration showed a mild progressive increase during pregnancy (peaking 29-32 weeks). The increase in lactoferrin concentration was, however, disproportionately small when compared with the concomitant pregnancy-related elevation in leucocyte count. The ratio of plasma lactoferrin concentration to leucocyte count therefore appeared to be abnormally low during pregnancy suggesting an acquired defect of lactoferrin release by leucocytes of pregnant women. It is unlikely that prolactin was the factor responsible for the reduced leucocyte release of lactoferrin. The lactoferrin:leucocyte ratio was already significantly reduced early in pregnancy at a time when prolactin concentration was relatively low. Furthermore, the correlation between prolactin concentration and both lactoferrin concentration and lactoferrin:leucocyte ratio was positive. Pregnancy appears to be associated with an acquired abnormality of leucocyte degranulation, the cause of which is not clear at present. PMID- 2588083 TI - Pre-examination psychotropic drug use by 5th-year medical students at the University of Cape Town. AB - Various aspects of psychotropic drug use by University of Cape Town 5th-year medical students during the final 4-week block of the year and the ensuing examination period were studied using a questionnaire. The response rate was 96.2%. Twenty-seven (17.8%) of the respondents indicated that they had used a total of 32 psychotropic drugs--18 used benzodiazepines, 6 used stimulants, 4 used beta-blockers and 3 used antidepressants. Fourteen students used the drugs daily or more frequently, while 10 had used psychotropic drugs before the period under investigation. Fourteen drugs were obtained from sources other than the prescription of a medical practitioner. Fourteen students used the drugs for insomnia. In 2 cases the purpose for which the drug was taken was not achieved. Six adverse drug reactions were reported. Implications of these results are explored. PMID- 2588082 TI - The influence of inborn athletic potential on choice of profession and exercise habits of paramedical students. AB - Twenty physiotherapy and 15 pharmacology students from the 2nd-year paramedical class were studied to determine whether inborn athletic potential had influenced their choice of profession. Each subject completed a questionnaire and performed a graded treadmill test to exhaustion to determine maximum oxygen consumption (VO2max), peak treadmill running velocity and ventilation threshold (VT). No difference was found between physiotherapy and pharmacy students in body mass, VO2max or running speed at VT, but physiotherapy students reached a higher peak treadmill velocity (P less than 0.01). Fewer pharmacy students participated in sport at university. To determine factors influencing participation in sport, students from both groups who exercised were compared with non-exercisers. Students who exercised had significantly higher VO2max, peak treadmill running velocity and VT, but differences were less than could be explained purely on the basis of superior genetic endowment. It is concluded: (i) that physiotherapy students do not have greater inborn athletic potential than pharmacy students; (ii) that exercising students show physiological adaptations compatible with a higher level of 'fitness', and (iii) that whereas lack of inborn athletic potential is not the reason why some students do not exercise regularly at university, inborn athletic potential may determine those who will exercise competitively. PMID- 2588085 TI - Lung function screening in industry. AB - Regression equations for forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) for 518 black factory workers on the Transvaal highveld were calculated from data obtained during routine lung function testing at an asbestos cement factory. Only those subjects with clinically and radiologically normal lungs were accepted for the study. The lung capacities of the 60% who were light smokers were not significantly affected. Years of dust exposure were included as a separate independent variable and its contributory effect, after age had been allowed for, was insignificant. The final combined regression equations are considered to be representative of healthy black men on the Transvaal highveld. The values of FVC calculated from these equations were compared with values derived by other authors and, in view of the differences found, it was concluded that predicted values for black workers derived from regression equations for white subjects should not be used for industrial screening purposes. Group specific equations should be followed when using lung function testing for definitive clinical diagnosis or academic research. The equations suggested for black South African men are FVC = 0.055 (height in cm) - 0.016 (age in years) - 4.502 and FEV1 = 0.043 (height) - 00023 (age) - 3.006. PMID- 2588084 TI - Prediction equations for lung function in black industrial workers at Palabora Mining Company. AB - In the course of a study on the health effects of vermiculite, 653 black rural industrial workers had their lung function measured. Since the study revealed no health effects of their industrial environment, the group was used to determine prediction equations for black men. Vital capacity, forced vital capacity, forced expiratory volume in 1 second, and peak flow were appreciably higher than the predicted values for blacks in the USA. The predicted values were, however, lower than those reported for white non-smokers but significantly higher than those reported for a non-smoking group of black miners in South West Africa/Namibia. PMID- 2588086 TI - Incidence of tuberculosis among canning workers in the Boland, 1987. AB - Tuberculosis remains a serious public health problem in South Africa. Current control policy in industry relies on passive case-finding and regards industrial workers as at low risk. Analysis of tuberculosis among a canning factory population in the Boland demonstrated high rates of pulmonary tuberculosis, comparable to the high rates in the community, and an absence of the 'healthy worker effect'. Black men were at particular risk. An argument is made for a review of current practices in tuberculosis control based on a sound knowledge of risk profiles for particular industries. PMID- 2588087 TI - [Respiratory symptoms and specific IgE in workers on a maize farm]. AB - A questionnaire concerning respiratory symptoms was completed for 101 workers on a maize farm; 73 railway workers were used as a control group. Symptoms suggestive of allergy were found in 90% of the farm workers compared with only 4% of the control group. However, total IgE levels of the farm workers were not significantly raised and only 40% had positive radio-allergosorbent tests against specific allergens. Smoking seemed neither to reduce nor enhance symptoms. Fungal spores and bacteria in the vicinity were sampled and identified; no evidence of an allergic response to these agents was found. Mechanisms other than allergy must be considered responsible for the farm workers' symptoms. PMID- 2588088 TI - Statistical significance versus clinical relevance. Part I. The essential role of the power of a statistical test. AB - When comparing two treatment groups, hypothesis testing is widely used. However, clinical trialists should be more interested in statistical methods which elicit the magnitude of the differences between treatment groups, rather than a simple indication of whether or not the differences are statistically significant. Statistical significance does not necessarily imply clinical relevance. If the true difference between two treatment groups is so small that it is clinically irrelevant, a sample size can be found for which this difference is statistically significant. On the other hand, if the difference between treatment groups is statistically non-significant, it may still be clinically important. The limitations of conventional hypothesis testing of equal true means as such are highlighted. The need to control the power of the test--which takes into account the difference in treatment means which is considered important (clinically relevant) by the researcher--is discussed. PMID- 2588089 TI - Fatal neonatal meningitis and ventriculitis caused by multiresistant Achromobacter xylosoxidans. A case report. AB - Meningitis and ventriculitis in a 6-day-old neonate caused by a Gram-negative glucose-non-fermenting organism, Achromobacter xylosoxidans, was resistant to most antibiotics except ceftazidime and imipenem. The organism became resistant after 28 days treatment with ceftazidime. When the infant was 7 weeks old, imipenem became available but, in spite of 3 days of intravenous treatment, the organism was still recovered from ventricular cerebrospinal fluid and the child died. This would appear to be only the second report of neonatal meningitis caused by this organism. PMID- 2588091 TI - Malaria and pregnancy. PMID- 2588090 TI - Left ventricular myxoma. A case report. AB - A 27-year-old woman with a systolic ejection murmur caused by a left ventricular myxoma is described. The diagnosis of this potential fatal condition was made by echocardiography. The clinical differences between atrial and left ventricular myxoma are discussed. PMID- 2588092 TI - Gonococcal conjunctivitis. PMID- 2588093 TI - Lyme borreliosis in South Africa. PMID- 2588094 TI - Long-term penicillin in Sydenham's chorea. PMID- 2588095 TI - Anatomical basis of latissimus dorsi myocutaneous flap: clinical applications. AB - The anatomical study was carried out using 40 preserved cadaveric specimens of latissimus dorsi myocutaneous flaps. It included dissections, angiographies and tissue clearing after arterial injection with latex. The results proved that the dominant vascular supply, the thoracodorsal a., has an almost constant pattern of intramuscular distribution. In addition, there are two sets of segmental pedicles, from the intercostal and lumbar vessels, supplying the medial third of the muscle. The accurate localization of the intramuscular distribution of the thoracodorsal a. permitted the proper design of several island flaps with competent vascularity. The designed flaps were successfully applied in 10 cases for reconstruction of breast, axilla, neck and chest wall. PMID- 2588096 TI - An anatomic and dynamic study of the greater occipital nerve (n. of Arnold). Applications to the treatment of Arnold's neuralgia. AB - This study concerns the posterior ramus of the second cervical spinal n., or greater occipital of Arnold. By means of dissections in formalin embalmed cadavers, an attempt was made to define its winding course and to locate it in relation to clinical or radiographic landmarks, so as to provide a guide for infiltration of the nerve with local anesthetic. At the same time a dynamic study was made to elucidate the relations of the nerve to adjacent structures during the different movements of the neck. This allowed us to propose clinical tests of nerve involvement and to reveal the zones where the nerve is anatomically vulnerable. PMID- 2588097 TI - The arterial supply of the clavicle. AB - This report based on delineation of the arterial system with 3 component plastic material on 10 human cadavers describes the arterial supply to the clavicle. The study was performed in 2 parts. One part, which showed the total arterial supply to the clavicle and one part with selective injections of the relevant arteries, with the intention of finding a central nutrient arterial supply to the clavicle. Three arteries were found to supply the clavicle: the suprascapular a.; the thoracoacromial a.; and the internal thoracic (mammary) a. The main supply was primarily periosteal. No nutrient artery was found. PMID- 2588098 TI - Corrosion cast studies of the bronchial arteries. AB - The bronchial a. are the nutrient vessels of the lung. Despite being high pressure (systemic) vessels they are of very small size compared to the pulmonary a. and their side branches are normally so minute that they are extremely difficult to visualize during in vivo studies--yet these branches also supply many important mediastinal structures including the esophagus, trachea, lymph nodes, pericardium, aorta, and mediastinal parietal pleura. The bronchial a. can react vigorously to pathological changes in the lung by hypertrophy and increased flow and their precise anatomy has become of increasing importance with the development of interventional techniques involving the systemic circulation of the lungs. In order to demonstrate the distribution and extent of these vessels we have adopted a casting technique using injections of various colors of latex to distinguish between pulmonary a. and veins, bronchial a. and veins and their connections with the pulmonary vascular bed in both normal and diseased lungs. PMID- 2588099 TI - Biomechanics of the lumbar spinal nerve roots and the first sacral root within the intervertebral foramina. AB - This study consists of 3 sections: a descriptive study of the intervertebral foramen by dissection, supplemented by millimetric sections made with the cine microabrasive apparatus (patented) on 12 specimens frozen with liquid nitrogen; a study of the attachments of the roots made during manipulations testing the resistance to avulsion of the rootlets, the roots, the dural sheath and the fibrous expansions at the periphery of the intervertebral foramen; and a study of the mobility of the roots in the foramina during movements effected within and outside the spine. We concluded that the classical description of an intervertebral foramen as occluded by a taut membrane like a drum-head is false as only perforated expansions attach the root to the foramen. Further, the points for attachment of the roots are the dura mater and the fibrous expansion passing from the foramen to the sheath of the spinal n. Finally, from the aspect of mobility, there are 2 distinct compartments and movements in one are not perceived in the other compartment if the attachments are unbroken. These attachments are a barrier interposed between the two compartments. PMID- 2588100 TI - Radiologic study of the influence of zygapophyseal joint orientation on spinal injuries at the thoracolumbar junction. AB - The change from coronal to sagittal plane orientation of the zygapophyseal (facet) joints at the thoracolumbar junction, coupled with differences in lumbar and thoracic spine mobility, may predispose the T10 to L2 segments to injury. To test for an association between the level of injury and variations in orientation of the zygapophyseal joints, CT investigations of 44 spinal injured patients were studied. Of these, 28 sustained burst/compression fractures and 16 demonstrated a rotation injury with disruption to one or both zygapophyseal joints. Injuries were examined to determine whether more congruent "mortice" joints localised the segmental level of trauma. The Chi-square statistic was used: to compare the transitional characteristics of 44 clinical cases with a "normal" patient database (n = 630); to examine differences in transition patterns between the "compression" and "rotation" injury groups; and to compare the incidence of mortice joints between the clinical and normal series. A significant difference between the transition patterns of the clinical and normal series (p less than 0.001) appeared to account for the higher frequency of abrupt transitions in the 44 injury cases. No significant differences distinguished the transition patterns of the two injury groups. A higher incidence of mortice joints was demonstrated in the injury group compared with the normal population (p less than 0.02). These findings suggest that individuals with an abrupt transition have a greater predisposition to injuries at the thoracolumbar junction. PMID- 2588101 TI - The role of orbital wall morphological properties and their supporting structures in the etiology of "blow-out" fractures. AB - The stiffness and strength of the orbital walls are proportionally dependent on the anatomical structures which support and strengthen these walls from the opposite side. The medial wall is therefore strong due to the support of ethmoid cells. The floor is stronger the less surface there is and the more supported it is by trabeculae of the maxillar sinus. The strength of the upper and lateral walls are proportional to their thickness. The orbital floor is on the average the weakest, followed by the medial and upper walls. The lateral wall is the stiffest and the most rigid. Computed tomography (CT) has improved structural analysis of the orbital contents and orbital walls enabling the visualisation of superficial and deep soft tissues and bone structures. PMID- 2588102 TI - Bourgery's artery: anatomic basis for a new cutaneous skin flap (21.06.88). AB - Bourgery's artery, the first branch of the popliteal a., delivers further branches to the vastus lateralis and biceps femoris m., by its terminal cutaneous branch, supplies a large territory of the external surface of the thigh. This area can be mobilized as a skin flap pedicle to cover tissue losses in the knee area. PMID- 2588103 TI - CT scan of gastrointestinal tract using a new calcium-based contrast medium (Cal Scan) (17.03.89). PMID- 2588104 TI - Pseudotumor and lymphoid tumor: distinct clinicopathologic entities. AB - Although in the past some have considered lymphoid tumor to be a form of pseudotumor, clinical, radiologic and pathologic features show them to be distinct entities. Acute pseudotumor presents with abrupt, painful onset, and CT scan shows a diffuse process with no distinct mass to biopsy. Chronic or recurrent pseudotumor leads to a mass of fibrosis apparent on CT scan, which should be biopsied. Lymphoid tumor presents without pain, and orbital CT scan shows a homogenous mass that should be biopsied. Acute pseudotumor usually responds to steroids, but patients with chronic or recurrent pseudotumor may require low-dose radiation or immunosuppressive therapy. Lymphoid tumors that are classified as reactive lymphoid hyperplasia initially may be treated with steroids, followed by low-dose radiation if steroids are ineffective. Orbital lymphomas are treated with higher dose radiation and, perhaps, chemotherapy, if systemic disease is present. Reports of representative cases of acute and chronic pseudotumor and lymphoid tumor illustrate the distinguishing clinical, radiologic and pathologic characteristics of each type of tumor, and recommendations for management of each type are outlined. PMID- 2588105 TI - A new experimental model for secondary hyperparathyroidism. AB - We have developed an animal model to study the pathogenesis of secondary hyperparathyroidism by inducing stable uremia in Sprague-Dawley rats by selective microligation of terminal branches of the left renal artery, followed by right nephrectomy. After 4 weeks the animals were killed, the parathyroid glands were removed and weighed, and blood samples were obtained. Of 30 rats, uremia developed in 22 (73%; uremic group) and eight (27%) died or did not become uremic. A sham-operated group of 15 rats served as control (control group). Creatinine levels were 1.8 +/- 0.5 mg/dl in the uremic group versus 0.5 +/- 0.1 mg/dl in the control group (p less than 0.0001). Parathyroid glands were hyperplastic in all rats with uremia and were heavier than parathyroid glands of control animals (70.3 +/- 26 vs 19.1 +/- 8 micrograms; p less than 0.0001). In the group with uremia, parathyroid hormone levels were increased over those of the control group (112.6 +/- 13 vs 28.9 +/- 6.2 pg/ml; p less than 0.0001), whereas osteocalcin levels were similar (36.6 +/- 11 vs 37.5 +/- 1 ng/ml). Serum calcium, phosphate, and alkaline phosphatase levels were similar in both groups. Our model can be used to test hypotheses concerning the treatment of secondary hyperparathyroidism and the relative pathogenetic relevance of vitamin D deficiency and phosphate retention. PMID- 2588106 TI - Circadian rhythms for calcium, inorganic phosphorus, and parathyroid hormone in primary hyperparathyroidism: functional and practical considerations. AB - We obtained serial serum and urine samples from 14 patients with primary hyperparathyroidism both before and 3 to 9 months after excision of their parathyroid adenomas to (1) determine whether the circadian rhythms for calcium, phosphorus, and parathyroid hormone (PTH) previously described in normal human beings are disturbed in this disorder; (2) gauge the effect of surgical treatment on the patterns observed before intervention; and (3) ascertain whether time(s) of blood sampling can be defined for optimal biochemical detection of the disease. Significant rhythms for serum phosphorus, ionized calcium, PTH, urine phosphorus, and urine calcium were observed in many but not all patients before and after surgery. Nonetheless, collective analysis revealed the following: (1) diurnal patterns for serum ionized calcium, phosphorus, urine calcium, and urine phosphorus in patients with primary hyperparathyroidism both before and after surgery, whereas a rhythm for serum PTH was uniquely observed after surgical treatment; and (2) no significant correlation between preoperative serum ionized calcium and PTH but restoration of the expected reciprocal relationship between these variables after surgery. Although variability in individual expression of the rhythm for PTH precludes precise definition of a sampling "window" when hormone levels are likely to be highest, collection of data at points throughout the day helped establish the diagnosis of primary hyperparathyroidism in several patients with borderline serum biochemistries. PMID- 2588107 TI - Difficulties of parathyroidectomy after previous thyroidectomy. AB - Although the risks of reoperative thyroidectomy and parathyroidectomy have been well studied, the problems associated with parathyroidectomy after prior thyroidectomy have not been emphasized. Among a group of 282 patients who were treated for primary hyperparathyroidism in recent years at the University of Chicago Medical Center, 14 (4.8%) had undergone one or more previous thyroidectomies, and 6 others (2.1%) had undergone thyroid ablation with radioactive iodine as therapy for Graves' disease. Numerous difficulties were encountered during surgery in the postthyroidectomy group of patients as a result of scarring and fibrosis, prior recurrent laryngeal nerve injuries in 13%, the inability to known with certainty how many viable, normal parathyroid glands remained after previous operations, and the need for additional thyroid resection, mostly for associated malignant lesions. Preoperative vocal cord assessment, evaluation of prior operative and pathology reports, and localization studies with thallium-technetium scanning and ultrasonographic techniques were especially helpful. A "lateral approach" was used frequently during surgery. Each of these 14 patients was cured of the hyperparathyroidism. The postthyroid ablation group presented fewer intraoperative challenges, although in some patients the thyroid gland was virtually absent, which obscured the normal landmarks of the surgical field. Five of these six patients were cured of hyperparathyroidism. Parathyroidectomy after thyroidectomy presents many operative challenges to the surgeon and should be approached with the same care and concern that one reserves for a reoperative parathyroid operation. PMID- 2588108 TI - Hyperparathyroidism after treatment with radioactive iodine: not only a coincidence? AB - Review of medical records in 600 consecutive cases of primary hyperparathyroidism revealed 10 patients with a documented history of iodine 131 (131I) treatment. In seven cases 131I had been given because of Graves' disease and in three cases for ablation of thyroid remnants after tumor operations. All but one of the patients were women. Their age at the time of 131I treatment ranged from 21 to 72 years, and the interval to detection of hypercalcemia was between 3 and 27 years. It is noteworthy that all patients treated for Graves' disease had absorbed radiation doses large enough to cause permanent hypothyroidism, and half of them showed complete absence of the thyroid gland at subsequent operation for hyperparathyroidism. Furthermore, parathyroid adenomas had developed at the sites of thyroid remnants in cases with 131I ablation after tumor operations. Our findings support other observations indicating that not only external radiation but also radiation from 131I is a risk factor for development of hyperparathyroidism, and it is emphasized that age at the time of radiation treatment may be of decisive importance in this context. PMID- 2588109 TI - Intravenous and portal venous administration of modified donor antigen prolongs rat parathyroid allograft survival. AB - The effect of pretransplant (day -6) systemic intravenous or portal venous immunization with modified donor antigen combined with cyclophosphamide treatment (75 mg/kg on day -4) on rat parathyroid allograft survival was evaluated. Systemic intravenous preimmunization of Buffalo recipients with 10(8) untreated Lewis donor spleen cells plus cyclophosphamide resulted in 100% accelerated rejection of Lewis parathyroid allografts (mean survival time, 7.3 +/- 0.9 days vs 10.8 +/- 1.1 days for controls). Portal venous administration of untreated cells plus cyclophosphamide reduced accelerated rejection to 40% but could not prolong graft survival (10.8 +/- 2.7 days). Intravenous or portal venous preimmunization with heat-inactivated cells (45 degrees C for 60 minutes) plus cyclophosphamide also did not prolong graft survival, with accelerated rejection occurring in 20% and 40% of recipients, respectively. In contrast, preimmunization by either route with ultraviolet B-irradiated cells (UVB; 12,000 joule/m2) plus cyclophosphamide significantly prolonged graft survival (intravenous = 22.2 +/- 6.0 days and portal venous = 21.4 +/- 7.2 days; p less than 0.005), with no accelerated rejection. Preimmunization with UVB cells combined with cyclophosphamide was synergistic, because neither treatment alone prolonged allograft survival (UVB cell preimmunization only = 10.8 +/- 1.3 days; cyclophosphamide only = 12.6 +/- 2.6 days). The effect of UVB preimmunization was donor specific because third-party Wistar-Furth UVB cells had no effect on Lewis graft survival (12.5 +/- 2.9 days). We conclude that pretreatment with UVB modified donor antigen plus cyclophosphamide induces allospecific immune hyporesponsiveness and prolongs parathyroid allograft survival. PMID- 2588110 TI - Pseudogout as a clue and complication in primary hyperparathyroidism. AB - The pseudogout syndrome has been suggested to be a diagnostic clue of hyperparathyroidism or a complication after parathyroidectomy that abruptly relieves hypercalcemia. In this report of 20 patients who had pseudogout, eight had intermittent attacks of arthritis associated with chondrocalcinosis that led through the pseudogout syndrome to a confirmed diagnosis of primary hyperparathyroidism. In an additional 12 patients, the diagnosis of pseudogout was made in patients who suffered from acute arthritis after parathyroidectomy that relieved the primary hyperparathyroidism. The postoperative attacks were seen most commonly on or after the second day after surgery and were associated with the lowest point in serum calcium levels. Pseudogout occurred in one or more joints, often involving the knee. The diagnosis was proved by aspiration of joint synovial fluid in many of the patients and identification of calcium pyrophosphate dihydrate crystals. To estimate the incidence of pseudogout in the population of patients with primary hyperparathyroidism, these 20 patients were distinguished in 531 patients undergoing parathyroidectomy, for a 3.8% incidence of the pseudogout feature. No other markers of higher risk for this complication were apparent, including age, sex, biochemistry, or prior history. This collected experience suggests that (1) pseudogout is a biochemical entity associated with primary hyperparathyroidism and may offer a useful clue to the recognition of the disease in screening; (2) acute arthritis after parathyroidectomy is most likely pseudogout, and this complication occurs more frequently than has been recognized previously; (3) patients with hypercalcemia have a high incidence of calcium pyrophosphate dihydrate crystal deposition in articular cartilage (chondrocalcinosis); and (4) relative hypocalcemia after parathyroidectomy is a stimulus for crystal shedding into synovial fluid, which may precipitate acute attacks of pseudogout. PMID- 2588111 TI - Morphologic and functional studies to prevent graft-dependent recurrence in renal osteodystrophy. AB - The cross sections of hyperplastic glands removed during total parathyroidectomy in patients with renal osteodystrophy were classified on the basis of macroscopic and functional criteria. Diffuse (type 1) and nodular (type 2) glands could be distinguished macroscopically. Functional in vitro studies showed no significant difference in suppressibility and basal parathyroid hormone (PTH) secretion (61% and 74%, respectively). In both types of glands A, B, C, and D regions could be distinguished with use of a stereo magnifier (magnification, x10 to x16). In diffuse A regions containing stroma fat cells, PTH secretion could be suppressed optimally (more than 50% of maximum secretion) in more than 90% of all specimens in vitro. In diffuse B regions containing no fat cells, hormonal secretion could be suppressed in only 17% and 25%, respectively. Confined (oxyphilic or chief cell) nodules (C regions), only found in type 2 glands, could be suppressed in 18%. Nodules of "degenerating" oxyphilic cells (D regions), only found in type 2 glands, were suppressible, but the low PTH secretion indicated degenerative processes. Thus only fragments from A regions should be selected for autotransplantation. PMID- 2588112 TI - Tertiary hyperparathyroidism after renal transplantation: operative indications. AB - A retrospective analysis of our renal transplant population between 1981 and 1987 was undertaken to study the natural history of posttransplant hypercalcemia and to review indications and recommendations regarding the timing of parathyroidectomy. During this period, 1158 renal transplant procedures were performed in 1025 patients, with 819 allografts (71%) functioning currently. Posttransplant hypercalcemia greater than 10.5 mg/dl was associated with a longer duration of dialysis and developed in 227 patients, with onset of hypercalcemia occurring in 90% of these patients by 1 year. In 69% of these patients, spontaneous resolution of the hypercalcemia occurred between 6 months and 7 years after transplantation. A total of 42 patients with asymptomatic hypercalcemia are currently being followed up, with a mean serum calcium level of 11.0 +/- 0.41 mg/dl and a mean follow-up interval of 3.3 +/- 1.6 years since transplantation. Nine symptom-free patients with moderate hypercalcemia (12.0 to 12.4 mg/dl) more than 1 year after transplantation were identified. Five of these patients had spontaneous resolution of the hypercalcemia between 2 and 7 years. Fifteen patients with posttransplant hyperparathyroidism (6.6%) required parathyroidectomy--11 for symptomatic and four for asymptomatic hyperparathyroidism. One patient had symptomatic hyperparathyroidism despite the presence of normocalcemia. One symptom-free patient with significant hypercalcemia (serum calcium level, 14.7 mg/dl) underwent parathyroidectomy 3 months after transplantation. The remaining three symptom-free patients had serum calcium determinations of greater than or equal to 12.5 mg/dl more than 1 year after renal transplantation. Patients with pretransplant and posttransplant hypercalcemia required parathyroidectomy more frequently than did patients with only posttransplant hypercalcemia (18% versus 3.0%; p less than 0.001). An unusual finding was the occurrence of a single adenoma in two patients, which represents sporadic primary hyperparathyroidism in the patient undergoing renal transplantation rather than tertiary hyperparathyroidism. We recommend a conservative approach to posttransplant hypercalcemia, with surgery reserved for patients with symptomatic disease and patients with asymptomatic persistent hypercalcemia greater than or equal to 12.5 mg/dl more than 1 year after transplantation. PMID- 2588113 TI - Bone demineralization, a factor of increasing significance in the management of primary hyperparathyroidism. AB - The significance of bone demineralization was evaluated for 97 patients treated surgically for primary hyperparathyroidism since 1980. Of 31 patients studied by bone densitometry, 16 showed moderate to severe osteoporosis. In approximately 20% of the total group, bone demineralization, including a bone fracture problem in some, was the dominant or a major indication for operation. Serial bone studies in six patients taken preoperatively or in patients not operated on for primary hyperparathyroidism showed an average loss of bone mineral density of 0.9% per year, whereas in four patients treated surgically serial studies showed an average increase of 9.8% per year. Although estrogen intake reduced serum calcium levels, significant bone demineralization or fractures were present in four patients aged 40 to 59 years and in five patients more than 60 years of age who had taken estrogens for many years. We conclude that in primary hyperparathyroidism, bone demineralization (1) justifies surgical correction in a significant number of patients; (2) should be evaluated, especially in elderly women; (3) is not prevented by estrogen intake, which may instead confuse decision making; (4) is reversed after surgical correction, but suggestions of incomplete reversal emphasize importance of this factor; (5) should be considered in postoperative management; and (6) involves many variables. PMID- 2588114 TI - Cholelithiasis follows total gastrectomy in Zollinger-Ellison syndrome. AB - The frequent occurrence of cholelithiasis noted in the follow-up of patients who underwent total gastrectomy because of Zollinger-Ellison syndrome prompted us to study this phenomenon. Cholelithiasis is known to be more common after truncal vagotomy, with or without concomitant subtotal gastric resection, and the prevalence of gallstones in these patients is reported to be 16% to 38%. To date, however, no long-term study has investigated the prevalence of gallstones after total gastrectomy in patients with the Zollinger-Ellison syndrome. Since 1961, 26 patients with the Zollinger-Ellison syndrome have undergone total gastrectomy and were enrolled in a Medical College of Wisconsin Clinical Research Center protocol that allowed follow-up to assess the development of cholelithiasis. Eight patients had cholecystectomy at the time of total gastrectomy (seven patients had stones), leaving 18 patients with a normal gallbladder and no gallstones at the time of total gastrectomy. Four patients died early, two of surgical complications, one of tumor progression, and one of alcohol-related trauma. During follow-up, cholelithiasis has developed in 10 of 14 patients (71%) at risk; the mean time to gallstones was 6.3 years (range, 1.2 to 12.9 years). The predictable occurrence of cholelithiasis after total gastrectomy in patients with the Zollinger-Ellison syndrome suggests that cholecystectomy should be performed at the time of total gastrectomy. PMID- 2588115 TI - Fundusectomy-induced hypergastrinemia is not due to acid inhibition alone. AB - Hypergastrinemia is often attributed to loss of acid inhibition in the gastric antrum. Prior studies suggest, however, that hypergastrinemia after fundusectomy occurs earlier and to a greater degree than hypergastrinemia after total acid inhibition with high dose (8 mg/kg/day) famotidine. To explain the very early (0 to 21-day) gastrin response, 45 male Sprague-Dawley rats (250 to 350 gm) were equally allocated to fundusectomy alone, famotidine alone, and fundusectomy plus famotidine groups. Vena cava blood samples and antral tissue were harvested at 0, 4, 7, 9, 14, and 21 days. Fundusectomy produced dramatic, sustained hypergastrinemia as early as 4 days after the procedure. Minimal, transient hypergastrinemia was seen with famotidine treatment, but this returned to baseline in spite of total acid inhibition. Antral gastrin was comparable in all three groups at the intervals assessed. Furthermore, fundusectomy plus famotidine did not demonstrate a significant difference from fundusectomy alone. Thus it appears that fundusectomy produces early and sustained hypergastrinemia by a mechanism other than acid inhibition. PMID- 2588116 TI - Reversal of in vitro hepatic insulin resistance in chronic pancreatitis by pancreatic polypeptide in the rat. AB - In vitro isolated liver perfusion in a rat model of chronic pancreatitis (CP) has been shown to demonstrate hepatic resistance to insulin. The ability of pancreatic polypeptide (PP) to reverse the resistance to insulin on glucagon stimulated hepatic glucose production was therefore investigated in this model. CP was induced in 250 to 300 gm Sprague-Dawley rats by infusion of 50 microliters of 99% oleic acid into the pancreas via the common bile duct. After 6 to 8 weeks, isolated liver perfusion was performed on livers from both CP rats and sham operated control animals (n = 12, 14), both with and without PP administration. Glucagon infusion (100 pg/ml for 30 minutes) produced a five- to sixfold increase in hepatic glucose production. The integrated hepatic glucose output (IHGO) response to glucagon alone was comparable in pancreatic and sham-operated animals; during period 1 (0 to 10 minutes) IHGO was 7.1 +/- 0.5 mg/gm-min for sham-operated controls (n = 8) and 7.1 +/- 0.4 mg/gm-min for pancreatitic animals (n = 6) without PP treatment. Animals that received PP (100 ng intraperitoneally 5 hours before liver harvest and perfusion with 4.2 ng/ml from 10 to 30 minutes) demonstrated an IHGO for period 1 for the sham (n = 6) and pancreatitic animals (n = 6) of 5.6 +/- 0.6 and 4.8 +/- 0.8 mg/gm-min, respectively. Insulin infusion (100 microU/ml added to perfusate from 10 to 30 minutes) in CP livers without PP revealed impaired responsiveness to insulin; the ratio of period 3 (20 to 30 minutes)/period 1 IHGO was 110% +/- 5% in CP livers compared with 77% +/- 5% in sham controls (p less than 0.01). In contrast, PP treatment restored hepatic responsiveness to insulin to control levels; the period 3/period 1 IHGO was 75% +/- 13% in CP livers treated with PP, which was indistinguishable from the 67% +/ 9% response seen in sham-operated control animals. These data provide the first in vitro evidence of a primary hepatic glucoregulatory role of PP. Therefore PP deficiency may contribute to altered glucose metabolism through the induction of a reversible hepatic resistance to insulin. PMID- 2588117 TI - Gastrin-releasing peptide-, calcitonin gene-related peptide-, and calcitonin-like immunoreactivity in human breast cyst fluid and gastrin-releasing peptide-like immunoreactivity in human breast carcinoma cell lines. AB - To assess the role of growth factors in proliferative disorders of the breast, we assayed breast cyst fluid from 70 patients for calcitonin-related peptides. Cyst fluids (5.4 +/- 6.6 ml) (mean +/- SD) (n = 70) contained 10,499 +/- 8272 pg/ml of gastrin-releasing peptide (GRP)-like immunoreactivity in 66 of 70 samples. Calcitonin gene-related peptide (CGRP)-like immunoreactivity was found in 64 of 64 samples tested (3842 +/- 2048 pg/ml). Calcitonin-like immunoreactivity was detected in 47 of 69 samples (185 +/- 106 pg/ml). Significant correlations were found for GRP versus volume, CGRP, and calcitonin, for calcitonin versus volume and CGRP, and for CGRP versus volume. Extracts of two human breast carcinoma cell lines (MCF-7 and BT-20) contained measurable GRP-like immunoreactivity. We conclude that GRP-, CGRP-, and calcitonin-like immunoreactivities are present in human breast cyst fluid and that GRP-like immunoreactivity is present in two established human breast carcinoma cell lines. High concentrations of GRP-like immunoreactivity in both breast cyst fluid and breast carcinoma tissue, taken together with the known mitogenic and trophic activities of this peptide, support the hypothesis that GRP may be an important factor in human breast disease. PMID- 2588118 TI - Exclusive use of calcium channel blockers in preoperative and intraoperative control of pheochromocytomas: hemodynamics and free catecholamine assays in ten consecutive patients. AB - This study investigates the role of nicardipine hydrochloride in preoperative and intraoperative blood pressure control and intraoperative catecholamines (norepinephrine and epinephrine) release in 10 patients undergoing pheochromocytoma resection. Nicardipine was used orally in the preoperative period for either 1 or 8 days (60 to 120 mg/24 hr) and then was infused during anesthesia until tumor removal, continuously at a rate of 2.5 to 7.5 micrograms/kg/min, depending on systolic arterial pressure level. All patients were successfully operated on. No severe hypertensive crisis occurred during tumor manipulation, although several patients had a 3- to 85-fold (norepinephrine) and 3- to 40-fold (epinephrine) increase of catecholamines from baseline levels. Hemodynamics data suggest that nicardipine caused significant inhibition of vascular smooth muscle contraction (42% decrease in systemic vascular resistance); calcium-dependent catecholamines release was not inhibited by nicardipine infused as mentioned. Use of nicardipine may be recommended for perioperative and intraoperative control of pheochromocytomas and might substitute for routine alpha-adrenergic blockade. PMID- 2588119 TI - Idiopathic aldosteronism masquerading as discrete aldosterone-secreting adrenal cortical neoplasms among patients with primary aldosteronism. AB - The medical records of 32 patients with primary aldosteronism who underwent adrenalectomy at the University of Michigan Medical Center from January 1975 to February 1988 were reviewed. All 32 patients had the preoperative diagnosis of aldosterone-secreting adrenal cortical neoplasms. Based on pathology reports, however, 21 of 32 (66%) patients were confirmed to have adrenal cortical neoplasms. Ten of 32 (31%) patients had nodular hyperplasia, and 1 of 32 (3%) had diffuse hyperplasia. This report focuses on the results in 11 patients with idiopathic aldosteronism. In six of nine (67%) patients, aldosterone levels rose within 4 hours of patients assuming an upright posture after salt loading. Seven patients had selective adrenal venous aldosterone/cortisol ratios that were interpreted to lateralize to one adrenal gland; however, only four of seven (57%) had ratios of 3:1 or greater than the contralateral adrenal gland. In 6 of 11 (55%) patients, adrenal scans (NP-59) initially demonstrated unilateral uptake. Three of four computerized axial tomographic scans demonstrated a unilateral adrenal mass. Only 3 of 11 (27%) patients with idiopathic aldosteronism were normotensive after surgery. Four of 11 (36%) patients' conditions were improved, in that they became normotensive with antihypertensive medication. These data suggest that if both imaging and functional studies lateralize to one adrenal gland, it is reasonable to expect either a cure or an improvement after adrenalectomy among patients with primary aldosteronism caused by idiopathic aldosteronism. Unilateral adrenalectomy may be the treatment of choice in carefully selected patients with nodular hyperplasia causing primary aldosteronism. PMID- 2588120 TI - Sequelae of radiation facial epilation (North American Hiroshima maiden syndrome). AB - Radiation for benign problems of the head and neck area has been uniformly recognized as unacceptable practice. This includes epilation for facial hirsutism. Twelve such patients, recently encountered, have characteristic radiodermatitis facies and have demonstrated multisite neoplastic involvement- including skin, thyroid, parathyroid, salivary gland, oral cavity, facial skeleton, and breast--and have also undergone extensive dermatologic treatment of complications of radiodermatitis. There was one cancer death, and three patients are alive with cancer. Such patients have a superficial resemblance to the Hiroshima maiden group of young women who survived atomic bombing and experienced severe facial burns, necessitating extensive plastic surgery. As atomic survivors they are at increased risk for cancer of thyroid, salivary gland, lung, breast, bone marrow, and gastrointestinal tract. The North American Hiroshima maiden should warrant easy clinical recognition and require lifetime scrutiny for multisite neoplastic disease. PMID- 2588121 TI - Plasma free thyroxine concentrations in patients receiving levothyroxine for thyroid suppression. AB - The usual recommendation is to follow total triiodothyronine (T3) concentration during levothyroxine (L-thyroxine) therapy because 65% of clinically euthyroid patients receiving L-thyroxine have normal T3 but elevated total thyroxine (T4) levels. Because free thyroxine (FT4) is the metabolically active form of T4, our study was designed to determine whether FT4 by analog radioimmunoassay method is normal or increased in euthyroid patients receiving L-thyroxine. Twenty-seven clinically euthyroid patients, 5 males and 22 females, receiving L-thyroxine for thyroid suppression, were studied in a prospective protocol. Twenty-one euthyroid patients not receiving L-thyroxine served as controls. Samples were analyzed for T4, T3, T3 (RU), TSH, and FT4 by three analog methods. Mean FT4 levels were greater than control for all three assays. The percentage of patients with FT4 in the hyperthyroid range was 63% for assay I, 41% for assay II, and 52% for assay III. When patients were grouped by dose of L-thyroxine, FT4 levels were not significantly increased. Sixty-two percent of patients receiving L-thyroxine had T4 levels in the hyperthyroid range. T3 concentrations were not significantly greater in the L-thyroxine group when compared with control. In the L-thyroxine group, thyrotropin was significantly less than in the control group. FT4 concentration by analog method is in the hyperthyroid range in as many as 63% of clinically euthyroid patients receiving L-thyroxine. The use of FT4 to assess thyroid status may cause inappropriate adjustment of L-thyroxine dose. T3 level continues to parallel closely the physician's clinical impression and best represents peripheral metabolic status. PMID- 2588122 TI - Selective postoperative radioactive iodine treatment of thyroid carcinoma. AB - In a consecutive series of 234 patients with differentiated thyroid carcinoma of follicular cell origin (Hurthle cell tumors excluded), a radioactive iodine (131I) scan was obtained 3 to 6 months after thyroidectomy and 4 weeks after cessation of thyroid hormone treatments, only if extrathyroidal tumor extension or nodal or distant metastases were present. Twenty-one patients (9%) with 131I uptake of 3% or more (group 1) were treated with 150 to 200 mCi of 131I. Forty four patients (19%) with less than 3% uptake (group 2) and 169 patients (72%) without evidence of metastases or extrathyroidal spread (group 3) were treated only with thyroid hormone. All patients initially underwent total thyroidectomy and modified neck dissection if cervical lymph node metastases were present. Three patients in group 1 and one patient in group 2 had recurrent tumor with a mean follow-up of 8.9 and 8.4 years. There were no recurrences in group 3 with a mean follow-up of 7.2 years. Death rate from thyroid carcinoma was 5% in group 1 (one patient) and 0% in groups 2 and 3. In conclusion, 131I scanning and therapy may be omitted in patients with differentiated thyroid carcinoma in the absence of local tumor extension or regional or distant metastases. Therapy with 131I is not demonstrated to be of benefit in this population of patients. PMID- 2588123 TI - Clinical and biologic behavior of bone metastases from differentiated thyroid carcinoma. AB - Thirty (3.8%) of 780 patients with differentiated thyroid cancer seen between 1970 and 1987 had bone metastases. The primary tumor was follicular in 26 patients and papillary in four. Mean age at diagnosis was 61 years. The manifestation of bone metastases was the presenting symptom in 18 patients (60%). Treatment included total thyroidectomy, levothyroxine sodium therapy, and radioactive iodine treatments. Twenty-seven patients had bone metastases from the initial observation, with 44 sites involved. Of the sites, 27 (61%) were shown both on iodine 131 whole-body scan (WBS) and on x-ray film, 11 (25%) only on WBS, and six (14%) only on x-ray film. Multiple involvement was observed in 11 patients. The radiologic appearance was invariably osteolytic. Serum thyroglobulin was elevated in all patients. After radioactive iodine, no WBS+/X ray+ metastases showed a complete response, although a sclerotic border was noted in several cases, whereas six WBS+/X-ray- lesions were no longer detectable by WBS. Treatment with radioactive iodine and bone surgery resulted in a complete cure in three patients and in a reduction of tumor mass in three. Twenty-one (70%) of the patients died of thyroid cancer after a mean survival of 86 months. Of the nine patients still alive, two are free of disease, three have a good quality of life, and four have severe disability. PMID- 2588124 TI - TSH binding correlates with TSH-stimulated thyroid adenylate cyclase activity in human thyroid tissues. AB - Thyroid-stimulating hormone (TSH) stimulates adenylate cyclase (AC) activity and the growth and differentiation of thyroid cancers of follicular cell origin. Thyroid neoplasms generally have higher TSH-stimulated AC activity than normal thyroid tissue from the same patients. To determine whether differences in TSH receptors could account for the differences in AC activity, we studied the 8000 g membrane particulate fraction from 28 thyroid tissues (10 papillary carcinomas, 6 multinodular goiters, 4 follicular adenomas, 3 follicular carcinomas, 2 Graves, 1 normal, 1 Hurthle cell adenoma, and 1 thyroiditis). TSH receptors were measured by competitive inhibition using radioactive iodine-labeled bovine TSH (125I bTSH). Maximal binding capacity (Bmax) and dissociation constant (Kd) were calculated by Scatchard analysis. AC activity was measured by the conversion of alpha-[32P]-ATP to [32P]-cAMP in the maximally (300 mU/ml) TSH-stimulated state. The basal and forskolin-stimulated (100 mmol/L) AC activity were also measured, and the ratios to TSH-stimulated AC activity were calculated (TSH/Basal ratio and TSH/Forskolin ratio). We found a strong correlation between the percent specific binding (%SB) of 125I-bTSH and TSH/Basal ratio (r = 0.70, p = 0.0001), between Bmax and the TSH/Basal ratio (r = 0.71, p = 0.001), between %SB and TSH/Forskolin ratio (r = 0.44, p = 0.02), and between Bmax and TSH/Forskolin ratio (r = 0.65, p = 0.0002). This strong correlation between TSH binding and the TSH-stimulated AC activity suggests that in some thyroid neoplasms the higher AC response to TSH may be due to an increased number of TSH receptors. PMID- 2588125 TI - Long-term follow-up of patients with benign thyroid fine-needle aspiration cytologic diagnoses. AB - Reliance on fine-needle aspiration (FNA) of the thyroid as the key determinant whether to observe only or proceed surgically is predicated on achieving a minimal false-negative error rate (the incidence of malignant disease in nodules diagnosed benign by means of FNA). To provide convincing data that malignant disease has not been overlooked requires extended follow-up on a large number of patients with cytologically benign lesions. The intent of our study was to assess the long-term accuracy of thyroid FNA-based diagnoses--particularly with respect to false-negative errors. From our total experience of more than 8000 patients, we reviewed the cases of 680 patients who underwent FNA in 1980, the first year we used it clinically. Follow-up information was obtained on 641 (94%) of the patients with a mean time since FNA of 6.1 years. Benign cytologic findings were reported on 439 (68%) of these patients, and only three (0.7%) had false-negative diagnoses. The false-positive rate was 0% for the 24 (4%) patients with positive aspirates. FNA is a safe, reliable, effective means of accurately discriminating benign from malignant thyroid lesions. PMID- 2588126 TI - Primary hyperparathyroidism and urolithiasis: concomitant surgical management. AB - Urolithiasis occurs in about 20% of patients undergoing cervical exploration for primary hyperparathyroidism. A small number of these patients may require surgical removal of the renal stones because of either obstruction or infection. The traditional surgical modalities for stone removal have been replaced by extracorporeal shock-wave lithotripsy, ureteroscopic stone removal, and percutaneous lithotripsy. During the period 1980 through January 1989, 22 patients underwent combined cervical exploration for primary hyperparathyroidism and treatment of renal or ureteral stones with a single general anesthetic at our institution. This study demonstrates that this approach can be performed safely with a high success rate and negligible morbidity and that this approach may have cost-effective implications. PMID- 2588127 TI - Primary hyperparathyroidism: a new experimental animal model. AB - Although potentially useful in the understanding of hypercalcemic states, a satisfactory animal model of primary hyperparathyroidism has not been developed. Models that use transplants of supernumerary parathyroid (PT) glands or chronic parathyroid hormone (PTH) infusion are not ideal for many reasons. We report a new animal model in which athymic nude mice were used as recipients of human PT tissue heterografts. Three groups received 14, six, or one piece of PT adenoma tissue, and one group received six pieces of normal PT tissue. The significantly higher PTH levels in mice that received adenoma heterografts versus those with similar amounts of normal tissue suggest that adenomatous tissue is functionally distinct. A dose-response relationship between induction of hypercalcemia and the number of pieces implanted was in evidence, although only a small percentage of the mice with high PTH levels developed hypercalcemia. This differential response could be the result of any of several factors: (1) loss of ability to secrete bioactive PTH, (2) differing secretion rates among donor adenomas, (3) variability in host responsiveness to human PTH, and (4) requirement of additional factor(s) to generate consistently the hypercalcemia characteristic of human primary hyperparathyroidism. PMID- 2588128 TI - [Treatment procedures in the vasoconstrictive form of hypertension using calcium antagonists in relation to their effect on kidney function]. AB - Single sublingual administration of nifedipine at a dose of 20 mg to patients with essential hypertension (EH) with subsequent hemodynamic observation every hour for 4 h resulted in the reduction of systolic and diastolic arterial pressure (AP) by 10-15%, arteriolar tone (AT) by 30-40%. Renal metabolism was assessed by the presence of slow isoenzymes of carbonic esterases in urine. They were absent in healthy persons; before nifedipine administration they were detected in 62% of cases, after it--in 22%. Regular administration of nifedipine (30-60 mg/day) and verapamil (160-240 mg/day) in a less severe course of EH (AT less than 4500 conv. units) improved the renal blood flow decreasing AT and AP. Severe EH (AT greater than 4500 conv. units) was characterized by cases of inadequate action of the drugs: dramatic reduction of ERF was followed by a rise of AT and AP which could be accounted for by excessive vasodilation at the 1st stage with further development of the renal steal syndrome and a rise of AP and AT. In such cases lower doses of nifedipine, the combination of verapamil with hydrochlorthiazide and verapamil with prazosin hydrochloride were more effective; the combination of nifedipine with propranolol did not prevent a negative effect on the kidneys and was ineffective in high AT. PMID- 2588129 TI - [The working requirements for blood components in clinical practice]. PMID- 2588130 TI - [Systemic oxygen transport in patients with myelotoxic agranulocytosis]. AB - The paper presents data on central hemodynamics, blood pulmonary shunting and evaluation of oxygen transport in 30 patients with myelotoxic agranulocytosis. In early agranulocytosis (fourteen cases) there was evidence of a drastic increase in pulmonary shunting, reduced stroke and cardiac indices, oxygen transport and its tissue utilization. By day 5-6 the disturbed parameters returned to normal values. It is noted that a phasic course of agranulocytosis implies time-related differential therapy. PMID- 2588131 TI - [Experience in treating patients with hairy-cell leukemia with a Soviet genetically engineered interferon]. PMID- 2588132 TI - [A case of secondary late arterial hemorrhage in a female patient with autoimmune thrombocytopenia]. PMID- 2588134 TI - [A combination of malignant mesothelioma of the pericardium with chronic lympholeukemia]. PMID- 2588133 TI - [Enhancement of the efficacy of thrombocyte transfusion in aplastic anemia by the use of plasmapheresis]. PMID- 2588135 TI - [The clinical characteristics of hematosarcoma with primary skin involvement]. AB - As many as 90 patients suffering from hematosarcomas associated with primary skin lesions were examined. This patients' group did not include patients with mycosis fungoides or with Sezary's syndrome. The clinical picture, ways and stages of the spreading of skin hematosarcomas were reviewed. Damage to the internal organs outstripped lymph nodes injuries in 1/3 of the patients. Half of the patients followed up until their death died at the height of acute leukemia. The survival appeared relatively high: the median period turned out to be 51 months, whereas 33% of the patients survived for 10 and more years. The survival was influenced by the sex and age of the patients as well as by the histological disease variant. PMID- 2588136 TI - [Chemoradiation treatment of patients with aggressive non-Hodgkin's lymphomas in stages I to II of the disease]. AB - Altogether 91 patients underwent treatment. Polychemotherapy (COP, ACOP) and radiotherapy were provided to 43 patients. Of these, 26 patients were irradiated locally and 17 were subjected to extensive radiation. Radiotherapy was given to 48 patients. Of these, 36 patients were subjected to irradiation of the local lesions whereas 12 underwent extensive radiation. Complete remissions were attained in 81 and 75% of the patients, respectively. The 5-year survival amounted to 65 and 34% (p less than 0.05), the 5-year survival without any relapses to 55 and 25% (p less than 0.01). In the IA stage, the 5-year survival was 89 and 44% (p less than 0.05) and the 5-year survival without relapses 63 and 13% (p less than 0.05). In the IIA stage, a statistically significant increase of the 5-year survival was also reached. No material differences could be seen in the results of the treatment depending on the scope of radiation. Drug + radiation treatment turned out most effective for the local stages of aggressive non-Hodgkin's lymphomas. PMID- 2588137 TI - [3 clinico-hematologic variants of hairy-cell leukemia]. AB - Analysis of the disease course in 17 patients afflicted with hairy-cell leukemia enabled the authors to specify 3 clinico-hematologic variants of the disease: a typical or a splenic one (with a predominant injury to the spleen), an atypical or bone marrow one (with a predominant injury to bone marrow), and a hypoplastic one. The bone marrow variant was characterized by the most pronounced leukemic injuries to bone marrow, severe bacterial complications, and the most unfavourable prognosis. The remaining variants were marked by their own individual features and ran a more favourable course. The division of hairy-cell leukemia into 3 variants promotes the improvement of the disease diagnosis and the elaboration of the optimal treatment policy in each specific case as well as the disease prognosis. The pathogenetic heterogeneity of the hairy-cell leukemia variants is discussed. PMID- 2588139 TI - [Intensive therapy and massive lesions]. PMID- 2588138 TI - [Immunoregulating effect of prostaglandins on the course of chronic lympholeukemia]. AB - A study was made of the effect of exogenous prostaglandins E1, E2 and E2 alpha on the proliferative response of lymphocytes in blast transformation with PHA according to the changes in permeability for 3H-thymidine, 3H-thymidine incorporation into DNA, 3H-uridine into RNA and 3H-leucine into protein in 7 patients with stable and in 17 patients with progressive B-chronic lymphoid leukemia (B-CLL). The progression of B-CLL was marked by the lack of the regulating effect of PG on lymphocytes. In stable lymphoid leukemia, an inhibitory action of PG on lymphocyte proliferation could be seen. The characteristics of the lymphocyte responses in patients with B-CLL were employed for individual prediction of the disease course. PMID- 2588140 TI - [The role of free oxygen radicals in the pathogenesis of Fanconi's anemia]. AB - The authors describe the results of a study into antioxidants (superoxide dismutase and catalase) and production of the active forms of oxygen (superoxide anion radical, hydrogen peroxide, hydroxyl radical, and singlet oxygen) by blood and bone marrow leukocytes from patients with Fanconi's anemia. The generation of the active forms of oxygen was induced by silica particles while the formation of radical products was recorded by means of luminol-dependent chemiluminescence. Unbalanced excessive production of oxygen radicals such as hydroxyl radicals combined with a decrease in the activity of antioxidant defence enzymes was discovered. It is believed that it is this circumstance that causes the derangement of the membranous structures and multiple breakdowns in the hereditary apparatus. It is suggested that antiradical preparations may be applied to correcting therapy of patients with Fanconi's anemia. PMID- 2588141 TI - [A method for the early detection and treatment of patients with iron deficiency states]. AB - In order to optimize the identification of persons with iron deficiency during mass prophylactic screenings, a diagnostic algorithm using a unified questionnaire was proposed and introduced into medical practice. During 1985 1987, a total of 3655 women aged 18 to 54 years belonging to different occupational groups filled in questionnaires at an industrial enterprise of Novosibirsk. The women were distributed into several groups: group I was made up of normal persons, group II of persons at risk, group III of persons with latent iron deficiency, group IV of persons with iron deficiency anemia, and group V of patients with continuously relapsing iron deficiency anemia refractory to therapy. Taking into account the groups indicated, the diagnostic and the treatment and prophylactic measures have been elaborated. PMID- 2588142 TI - [Autoimmune reactions against interleukin-2 receptors in patients with blood system diseases and in experimental Rauscher retrovirus leukemia]. AB - Apart from autoimmune reactions, antibodies to IL-2 receptors were identified in blood sera of linear mice during leukemogenesis. It is indicated that in the course of leukemia establishment, there can be demonstrated antibodies capable of blocking IL-2 receptors on the membrane of activated T lymphocytes and inhibiting IL-2-dependent proliferation of T cells. The blood sera of patients suffering from chronic lymphoid leukemia, acute lymphoblastic leukemia, lymphocytomas, pure red-cell aplasia, and aplastic anemia showed antibodies against IL-2 receptors. Out of the total number of 52 patients, 23 demonstrated those antibodies. The data obtained should be taken into account in the patients' management using IL 2. PMID- 2588143 TI - [Erythropoiesis inhibitor in the plasma of patients with hemopoietic dysplasias]. AB - Altogether 21 patients were examined for an erythropoiesis inhibitor contained by the IgG fraction of the blood plasma. All these patients suffered from hemopoiesis depression. The inhibitor identified in the immunoglobulin fraction of the blood plasma of 40% of the patients manifested itself at the stage of erythroid precursors of bone marrow cells. The role of the humoral inhibitor in the development of erythropoietic disorders in these patients is under discussion. PMID- 2588144 TI - [Intensive plasmapheresis (programs, laboratory monitoring, complications)]. AB - Experience gained with the use of plasmapheresis in 336 children with different diseases is described. In patients with bacterial and inflammatory processes, the effect was attained after the first plasmapheresis session. Acuity of the immunomediated processes decreased after exfusion of 2-3.5 volumes of the circulating plasma. The replacement of the exfused plasma by protein blood preparations was made only in patients with hepatodystrophy, bacterial and inflammatory diseases, and immune complex diseases combined with the signs of consumption coagulopathy. After a course of plasmapheresis there was a significant lowering of total protein, albumin and immunoglobulin G. The reduction of the content of hemoglobin and red blood cells was related to hemodilution Iron homeostasis remained unchanged. The use of plasmapheresis in atopic dermatitis without preventive administration of an antibiotic is associated with the risk of the development of post-catheterization thrombophlebitis. PMID- 2588145 TI - [The problems of plasma substitution in performing therapeutic plasmapheresis (an evaluation of the efficacy of plasma substitute media and the methods for obtaining them)]. AB - The analysis of 3700 plasmaphereses (AP) performed in 692 patients permitted the authors to develop the basic principles and policy of plasma substitution for various groups of patients. The use of protein preparations and fresh frozen plasma is believed essential in intensive plasmapheresis in patients with immunomediated disorders and DIC syndrome, respectively. Potentialities of selective therapeutic PA are discussed. PA criteria should be based on the patient's state, therapeutic aims, circulation parameters, laboratory data. PMID- 2588146 TI - [The correction of hemodynamic disorders of the lesser circulation in patients treated by programmed hemodialysis]. PMID- 2588147 TI - [The significance of early dysfunction of the transplanted kidney]. AB - The paper is concerned with the results of 39 transplantations of the kidney. All the patients received two basic immunosuppressants, namely prednisolone in a dose of 30 mg/day and Cy in a dose of 10-12 mg/kg a day. Within 6 to 11 months, the recipients' survival amounted to 82.5%, that of the organs to 84.5%. In 63.1% of the patients, immediate function of the transplant could be observed. It has been demonstrated that delayed function of the transplant was conjugated with reduction of the survival of the organs and recipients as well as with decrease of the quality of transplant functioning. Delayed function of the transplant might be determined not only by ischemic but also by immunologic injuries to the organ. PMID- 2588149 TI - [A method for determining the cyclosporin A concentration in capillary blood]. AB - A new method is described, which enables one to follow the blood concentration of CyA in patients living in remote regions, being far away from the transplantation hospitals. The method is based on the use of chromatographic paper FN-17 intended for application of the patients' blood spots. The pieces of paper with dried blood spots are sent by post to the laboratory where CyA is extracted from the spots, followed by the CyA concentration measurement with the aid of RIA. A procedure has been elaborated, permitting the measurement of the CyA concentration in patients with a poor access to the veins. PMID- 2588148 TI - [Late results of the treatment of acute granulocytic leukemia in adults]. AB - Eighteen patients with acute granulocytic leukemia (MI-1, M2-10, M3-1 and M4-6) underwent AdOAP treatment. Complete remissions were achieved in 10 out of the 18 patients (55.6%), 3 patients proved resistant, 5 had died prior to recovery of normal hemopoiesis. Three lethal cases are attributed to the results of the therapy complications. Median duration of complete remissions reached 17.5 months. Two patients have been in remission over 3 years. Reduced duration or intensity of the induction therapy failed to diminish frequency of lethal complications due to progressive cytopenia. PMID- 2588150 TI - [Quantitative determination of erythrocyte membrane glycoproteins as a characteristic of the atherosclerotic process]. PMID- 2588151 TI - [Effect of specific immunotherapy on the structural properties of the lymphocyte membranes in atopic diseases]. AB - 3-Methoxybenzathrone (MBA) fluorescence was used to explore the structural properties of blood lymphocyte membranes in patients with atopic bronchial asthma and pollenosis treated by specific immunotherapy. An analysis was made of the relationship between the changes in MBA fluorescence and the blood counts of T and B lymphocytes as well as the clinical efficacy of the treatment. As a result of the treatment, the patients manifested an appreciable increase in the MBA fluorescence intensity towards normal and higher limits, provided the results of the treatment were beneficial. In case the treatment effect was unsatisfactory, MBA fluorescence diminished. The rise of MBA fluorescence in lymphocytes was not induced by the changes in the cell counts in the populations. The treatment effect on the membranes remained unchanged in subsequent exacerbation. The use of MBA permits an objective and early assessment of the results of specific immunotherapy. PMID- 2588153 TI - [Chronic constipation and its treatment]. AB - Altogether 850 patients suffering from chronic constipation were examined. Of these, 80% only showed functional changes in the intestine, 5% lost the defecation reflex, and 15% manifested inflammation-induced lesions in the intestine. 80% of the patients demonstrated symptoms of dysbacteriosis. Multimodality treatment appeared to produce an appreciable effect in the majority of the patients. As a result many of the patients gave up laxatives. PMID- 2588152 TI - [Current trends in hospital nutrition. The initial experience of the use of a main basic diet]. PMID- 2588154 TI - [The efficacy of the natural antibacterial preparation chlorophyllypt in the combined treatment of acute lung abscesses]. AB - The complexity of the treatment of acute suppurative pulmonary diseases has been aggravated recently by the growth of microbial resistance to antibiotics and enhancement of the allergy incidence among the population. This circumstance restricts the use of antibiotic on a broad scale in clinical practice and makes the researchers go in studies of adequate substitutes. In the given case, use was made of chlorophyllipt. It was given to patients by intravenous drip in the form of a 0.25% solution based on saline twice a day. To increase local deposition of the administered antimicrobial drug in the affected area, interstitial electrophoresis was employed. In the patients' group on chlorophyllipt, the clinico-laboratory and x-ray parameters returned to normal earlier. Chlorophyllipt was noted to produce an immunocorrective action characterized by the normalization of the absolute count and percentage of E-RFC and theophylline resistant-RFC. This action could not be observed in the patients' group receiving only antibiotics. PMID- 2588155 TI - [The effect of intra-articular treatment with corticosteroids, polyvinylpyrrolidone and dimethyl sulfoxide on the composition of the synovial fluid in patients with rheumatoid arthritis]. AB - Synovial fluid (SF) contained by the knee joint from 102 patients (80 with rheumatoid arthritis, 12 with osteoarthrosis, 10 with posttraumatic arthritis) and controls was studied for cytosis, activity of acid phosphatase, N-acetyl-beta D-glucosaminidase, and cAMP and cGMP content. In 18% of the cases, the local corticosteroid treatment of patients with RA produced no beneficial effect. To treat RA and OA patients, dimethylsulfoxide (DMSO, 5 ml of 20% solution) and polyvinylpyrrolidone (PVP, 5 ml of 15% solution) were administered intra articularly. In OA patients, injection of DMSO and PVP provided a good therapeutic effect. In RA patients, injection of DMSO produced a beneficial antiinflammatory action but it appeared short-term. The use of PVP in RA patients with pronounced local process enhanced synovitis symptoms, entailed an increase of the SF amount and cytosis, did not reduce the activity of lysosomal enzymes, and produced a negligible effect on the level of cyclic nucleotides. A mixture of DMSO (1 ml of 100% solution) and PVP (5 ml of 15% solution) applied to the treatment of RA patients exerted a favourable action on the local process in the joint, namely reduced all the parameters mirroring the intensity of inflammation. PMID- 2588156 TI - [Cases of the dangerous arrhythmogenic action of ethacizine]. PMID- 2588157 TI - [The clinical efficacy of donor plasma with an elevated titer of endotoxin antibodies]. PMID- 2588158 TI - [The repeated development of acute kidney failure in a patient with chronic recurrent rhabdomyolysis]. PMID- 2588159 TI - [Common variable immune deficiency]. PMID- 2588160 TI - [Disorders of heart rhythm in pregnant women. Is it necessary and is it possible to treat them?]. PMID- 2588161 TI - [The use of naniprus (sodium nitroprusside) in therapy-resistant arterial hypertension]. AB - Naniprus (sodium nitroprusside) was shown to be clinically effective in the treatment of arterial hypertension and to have a favourable effect on the central and peripheral hemodynamics (a decrease of the total peripheral vascular resistance, of the energy consumption by the myocardium, an increase of the stroke volume, stroke index, and cardiac output). It is concluded that naniprus can be used for arterial pressure correction in the treatment-resistant patterns of hypertension, especially in combination with beta-blockers preventing the "after-action effect" (ejection at the moment of catecholamine infusion discontinuance). PMID- 2588162 TI - [Evaluation of obzidan efficacy in patients with unstable stenocardia]. AB - Altogether 75 patients (males aged 31 to 67 years) with unstable angina pectoris were subjected to transcutaneous pacing to measure the coronary reserve level before and after administration of obsidan (propranolol) in a dose of 40 mg. The area and depth of ischemia were found to be noticeably decreased, which was appraised according to 35 precordial leads on the ECG regardless of the unchanged "double product". It is concluded that not only the reduction of the heart rate and afterload but also their effect on the functional factors of angina pectoris are implicated in the mechanism of the anti-ischemic action of the beta-blockers. PMID- 2588163 TI - [Prolonged-action theophylline in the treatment of bronchial asthma]. PMID- 2588164 TI - [The late results of aspirin treatment in patients with aspirin-induced bronchial asthma]. AB - The paper treats long-term results of aspirin treatment of patients with aspirin induced bronchial asthma. The data obtained indicate that in this patients' group, the beneficial effect of aspirin treatment is also preserved after its withdrawal at any rate within up to one year. The authors have every reason to believe that such a treatment is unlikely to be applied for life. PMID- 2588165 TI - [The role of disorders of copper and zinc homeostasis in the pathogenesis of bronchial asthma]. PMID- 2588166 TI - [The effect of calcium antagonists on pulmonary hemodynamics in patients with chronic bronchitis with manifest and latent pulmonary hypertension]. AB - Catheterization of the pulmonary artery and radiocirculography were used in 30 patients with chronic bronchitis (CB) in order to study changes in hemodynamics induced by intravenous injections of 5 and 10 mg verapamil or by 4-5 weeks of the treatment with finoptin and corinfar. Out of 47 studies, 22 (47%) showed a positive effect which was primarily recorded in patients (72%) suffering from apparent pulmonary hypertension (PH). The effect manifested itself in the form of a decrease in the total pulmonary resistance and/or in the mean pulmonary arterial pressure. In 13 cases (27%), the effect turned out negative. Meanwhile 12 cases (26%) demonstrated no effect at all. A beneficial effect was mostly recorded after administering 5 mg verapamil, whereas administration of 10 mg verapamil and prolonged use of finoptin and corinfar produced varied actions, with the negative effect being observed even more frequently as compared to the positive one. The pattern of the pulmonary hemodynamic response to a single intravenous injection of verapamil was also preserved in 60% of cases undergoing continuous treatment with finoptin and corinfar. Calcium antagonists can be used for the treatment of PH in patients suffering from CB. At the same time it is required that all the patients may be necessarily examined for hemodynamics. PMID- 2588167 TI - [Experience with the use of vilozen in patients with bronchial asthma]. AB - The results of the use of vilozen in the treatment of bronchial asthma patients are presented. The efficacy of the drug for asthma of different genesis is demonstrated. Vilozen stimulates functions of cellular immunity and produces a moderate inhibitory effect on phagocytosis function. The drug is contraindicated in the treatment of patients with bacterial infection and pronounced obstructive syndrome. PMID- 2588168 TI - [The importance of studying the regulatory mechanisms of HCl secretion in patients with duodenal peptic ulcer]. PMID- 2588169 TI - [Clinical pharmacology and problems of drug therapy in the clinical picture of internal diseases]. PMID- 2588170 TI - [The pathogenetic significance of prostaglandins in food poisoning and therapy questions]. PMID- 2588171 TI - [The effect of a hyperbaric oxygenation session on autonomic regulation of the heart in elderly patients with chronic circulatory failure]. PMID- 2588172 TI - [Isolated ultrafiltration of the blood in patients with refractory heart failure: the status of the renin-angiotensin-aldosterone system and the secretion of antidiuretic hormone]. AB - Isolated ultrafiltration was performed in 107 patients with refractory heart failure (HF) which developed in the presence of different cardiovascular diseases. The beneficial action of isolated ultrafiltration in 71 patients (68%) with refractory HF was determined by complex interaction of the effects provoked by ultrafiltrate removal. Among those effects of paramount importance was correction of secondary hyperaldosteronism and reduction of the concentration of antidiuretic hormone accompanied by the improvement of liver and heart functions. PMID- 2588173 TI - [The regulation of respiration by inspiratory resistance in patients with chronic lung diseases]. PMID- 2588174 TI - [Evaluation of the efficacy of laser irradiation in the combined treatment of patients with Bechterew's disease]. PMID- 2588175 TI - [The prognostic significance of basic risk factors of ischemic heart disease and its changes in carrying out preventive measures]. AB - The paper treats the results of an analysis of the assessment of the main risk factors within the framework of the program for multifactorial prophylaxis of coronary heart disease in the populations with varying involvement into preventive measures. Using standard methods altogether 6566 men aged 40-59 years were examined in the area of two district polyclinics with a purpose of diagnosing coronary heart disease and risk factors of its development. During 5 years, measures aimed at active primary and secondary prophylaxis of coronary heart disease were carried out in one of the groups. Prospective survey over the death rate has demonstrated that cardiovascular diseases rank the first in the structure of the death rate among the adult male population, with their portion being increased with age. Studies into the relationship between the death rate and the main risk factors in the population provided evidence that risk of the death from cardiovascular diseases rises with an increase in the systolic and diastolic arterial pressure, in the body weight index, and in total cholesterol. The active composite preventive measures brought about a significant reduction in risk of the death from cardiovascular diseases, in the incidence of the fresh cases of myocardial infarction, and brain stroke. At the same time the death rate of cardiovascular diseases dropped by 40.7% as compared to the expected one, the number of lethal cases due to various reasons by 12.7%, an the incidence of myocardial infarction and brain stroke by 18.8%. PMID- 2588176 TI - [Assessment of the risk of a fatal outcome in patients with stable stenocardia in a 5-year period (II)]. AB - Based on the examination of 377 patients with associated coronary heart disease and stable angina pectoris a rule of forecasting coronary death was developed. Computer was used to identify the weight values of different clinical signs, changes in the ECG taken at rest, bicycle ergometry test, coronarography and the deciding rule was deduced. Depending on the magnitude of the prognostic index (I2) groups of low, moderate and high risk of the lethal outcome were identified during the 5-year period. The schedule for coronary death forecasting permits its use at public health institutions. PMID- 2588177 TI - [A prospective multiyear study of the course of chronic recurrent pancreatitis]. AB - It was established during observation over time (within the period from 10 to 12 years) that the overwhelming majority of patients with chronic cholecystopancreatitis and primary chronic pancreatitis progressed to a different degree to enzyme-secreting pancreatic failure according to the pancreozymine tests. At the same time in 2/5 of all the cases, enzyme-secreting failure turned out substantial by the end of the indicated period. During the years of prospective studies, every tenth patient with chronic pancreatitis developed secondary diabetes mellitus. The degree of pancreatic enzyme secretion and carbohydrate metabolism abnormalities depended on the number of disease exacerbations suffered by the patient. Secondary gastroduodenal ulcers occurred in 27 out of 647 patients observed over time, and all the cases were associated with a considerable reduction of pancreatic bicarbonate secretion (according to the secretin test). Pancreatogenous pleural exudate was recorded in 1.4% of all the cases of chronic pancreatitis. During the observation period, 16 out of the 647 patients died from chronic pancreatitis associated with progressive exocrine pancreatic failure and malabsorption. PMID- 2588178 TI - [The diagnosis, clinical picture and treatment of acute radiation sickness in the victims of the Chernobyl Atomic Electric Power Station. II. Non-bone marrow syndromes of radiation lesions and their treatment]. AB - Out of 115 victims to the breakdown, 56 persons had radiation burns, 17 the intestinal syndrome, 80 the oropharyngeal syndrome, and 7 interstitial radiation pneumonitis. In the lethal outcome, of crucial importance were radiation burns (over 40% of the body surface) (19 persons) and radiation pneumonitis (7 persons). The grave intestinal and oropharyngeal syndromes were accompanied by other fatal manifestations of radiation injuries. Hemoperfusion, plasmapheresis, continuous heparinization and administration of freshly frozen plasma did not bring about any improvement. The local use of different remedies under aseptic conditions was the leading method of the treatment of radiation burns in the acute period. Parenteral feeding turned out to produce a beneficial effect in the treatment of the intestinal and oropharyngeal syndromes. PMID- 2588179 TI - Texas/Oklahoma AIDS center funded for second year. PMID- 2588180 TI - Day care--the pediatrician's perspective. AB - Physicians are frequently called upon to make recommendations to parents about day-care arrangements, but may feel poorly qualified to give advice to parents. Widespread use of alternative care arrangements for young children has been the practice for only about 20 years. The impact of alternative care on children is continually being reevaluated, but certain aspects are clear. Quality of care varies greatly from setting to setting, and government guidelines do not ensure good quality. Physicians caring for children should be aware of the possible effects of day care on their patients and should be able to make recommendations to parents. Physicians also have an opportunity to serve as advocates for children in promoting quality alternative care arrangements. PMID- 2588181 TI - Pediatric AIDS: a new health problem on the Texas horizon. AB - The current epidemic of HIV infection/AIDS initially limited to homosexual males appears to be spreading through heterosexual transmission and intravenous drug abuse. Infants, children, and adolescents are affected. We examine the modes of transmission of HIV infection in this population and the impact the spreading of this infection in the pediatric age group will have on Texas. PMID- 2588182 TI - Rocky Mountain spotted fever in Texas, 1978 through 1987. AB - From 1978 through 1987, there were 397 laboratory-confirmed cases of Rocky Mountain spotted fever reported in Texas. The annual number of cases ranged from 21 cases in 1986 to 108 cases in 1983. A total of 262 cases were in males. Most of the patients (52%) were 19 years of age or younger. April through August were the months of onset of symptoms for 66% of the cases. Eighty-two percent of the infected patients were hospitalized; 14 patients died. An endemic focus of Rocky Mountain spotted fever exists in north central and northeastern Texas. PMID- 2588183 TI - Pediatric HIV infection/AIDS in Texas. PMID- 2588185 TI - Report of the TMA Task Force on Nursing shortage. PMID- 2588184 TI - Biologic response modifiers: understanding biologic systems. PMID- 2588187 TI - Physician's hazard: the OSHA man cometh. PMID- 2588186 TI - Rx nursing shortage: task force recommendations. PMID- 2588188 TI - What's new in liability insurance? PMID- 2588189 TI - Doctor calls for coordinated rural health care services. PMID- 2588190 TI - Physician recommends wallet card for patient data. PMID- 2588191 TI - AMA and TMA: partners for better health. AB - United States Rep Charles W. Stenholm (D-Tex) has warned physicians, "The AMA can be effective only if members of Congress are convinced that this group truly represents their constituents. Until the AMA represents a majority of its self proclaimed constituency, it won't be as effective as physicians across the country would like it to be." Texas Medical Association is the fourth largest delegation to the American Medical Association, but approximately 40% of the TMA membership does not belong to the national organization. Nationwide, approximately 60% of physicians have chosen not to join the AMA. TMA's House of Delegates recognizes the importance of a strong national organization and supports communication and recruitment activities to assure the state has maximum voluntary participation in the AMA. This article describes the AMA's activities as the physician's and the patient's advocate. PMID- 2588192 TI - Relapse of adult acute myelogenous leukemia isolated in testicle. AB - Isolated testicular relapse of acute leukemia, although common in children, is rare in adults. A 63-year-old man who had completed induction and intensification chemotherapy presented with unilateral testicular enlargement as the sole manifestation of biopsy-proven acute leukemia relapse. The infiltrative characteristics of acute monocytic leukemia and the anatomic barriers and location of the testicles may have provided a sanctuary from chemotherapy. PMID- 2588193 TI - Are we to blame for our own unhappiness with medicine? PMID- 2588194 TI - Pilot study report: obstetrical care by Texas family physicians. AB - Fewer family physicians are including obstetrics in their practices. This has caused concern about access to obstetrical care and has fueled the debate about the need for obstetrics curriculum in family practice residencies. Reasons frequently cited by previous research for this change in practice pattern include the rapidly escalating cost of liability insurance and the threat of lawsuit for obstetrical malpractice. The decrease in the availability of obstetrical care from family physicians has hampered access to obstetrical care, especially for rural Texans. Texas family physicians have not been surveyed previously about their obstetrical practices. For this pilot study I surveyed 205 of Texas' 4,700 family physicians and general practitioners (4%) about their past and present obstetric practices. The sample was randomly selected, and included both MDs and DOs. Of the 64.9% who responded, 28% were practicing obstetrics, 11% had never included obstetrics in their practices, and 61% had practiced obstetrics in the past. Forty percent of those who had discontinued obstetric practice did so after 1983. High malpractice premiums and fear of lawsuits were the most frequently chosen reasons for discontinuing the obstetric component of practice. Documenting this trend of decreasing availability of obstetrical care from family physicians, and sharing the data with policymakers, may help to prevent the disappearance of the family physician who delivers babies. PMID- 2588195 TI - AMA responds to decision to allow restrictions on abortion. PMID- 2588196 TI - Effect of lipanthyl in hyperlipoproteinaemic diabetic patients. AB - Diabetic metabolic disorder means, at the same time, a disturbed lipid metabolism. On the basis of this consideration the authors examined the drug in diabetic patients and found it to have a very advantageous effect. In response to the drug lipid parameters improved rapidly but after discontinuance of therapy these values deteriorated again which indicates the effectiveness of the product but calls the attention to the importance of continuous drug administration. PMID- 2588197 TI - Observations with Chinofungin powder. AB - Chinofungin powder was used in 75 recruits, in 40 cases for prevention, in 35 cases for the treatment of manifesting mycotic alteration. After a three-week treatment with the product recovery was obtained in 54.3%, improvement in 28.6% of the cases. No change was observed among the blastomycetic infection cases. In 5 of the 40 healthy individuals (12.5%) the cultivation became positive for fungus by the end of the three-week observations period. According to the opinion of the authors non-compliance was responsible for the infections which occurred during the preventive treatment. PMID- 2588198 TI - Observations in the course of the follow-up of Sumetrolim-treated patients. AB - The authors analysed the results of bacteriological examinations of 600 urine samples with special regard to the sensitivity of the different pathogenic agents to Sumetrolim (400 mg sulphamatoxazole + 80 mg trimethoprim per each tablet). Their observations were also summarized in tables. The effectiveness of Sumetrolim treatment (for 5 days daily 2 x 3 tablets, from the subsequent 10 days daily 2 x 1 tablet) used in 100 chronic prostatitis patients and in 100 patients suffering temporarily from chronic infection (who had undergone prostatectomy) has been analyzed. Sumetrolim has been found to be valuable in the urological practice especially in the treatment of chronic infections of long duration. Teh eventual side-effects of Sumetrolim have been discussed on the basis of references and own observations referring to the treatment of 200 patients. The therapy had to be discontinued in 21 cases, in 1 case because of toxicoderma responding well to therapy, in 3 cases because of mild cutaneous alteration, in 10 cases due to intensive diarrhoea, and in 7 cases because of other side effects. PMID- 2588199 TI - Use of Histodil injection in upper gastro-intestinal haemorrhages. PMID- 2588200 TI - Therapeutic usefulness of anteovin. AB - The therapeutic effect of Anteovin has been examined in 86 women suffering from cycle disorder and menstrual complaints, respectively. The majority of women wanted to control conception at the same time, consequently the use of the tablet served double purpose. According to the results of examinations biphasic hormone therapy regulates successfully irregular cycles, the side-effects do not hinder therapy and the contraceptive effect of therapy is also reliable. These favourable properties support the opinion accepted increasingly that multiphasic tablets are the drugs of choice for both therapeutic and contraceptive purposes. PMID- 2588201 TI - Use of peripheral dopamine antagonist (Motilium) in the treatment of dyspeptic complaints of different origin and in nausea, vomiting. AB - The incidence of dyspepsias and emesis occurring either as accompanying symptoms of gynaecological operations or as independent clinical conditions, therapeutic means for controlling these conditions and the mechanism of action and clinical usefulness of the dopamine antagonist domperidone have been discussed. The observations with this drug in 68 women suffering from dyspepsia and in 94 cases of emesis of different etiology have been analysed. The author stated that Motilium is the drug of choice in the treatment of complaints due to motility disorder of the upper gastroduodenal tract, that the patients tolerate the drug well, and that it's use does not hinder the treatment of the primary gynaecological disease, pre-operative therapy, anaesthesia, and postoperative care of the patients. Its antiemetic effect depends on the time of intake which is a disadvantage of oral application. PMID- 2588202 TI - Examination of Cavinton effect in elderly diabetic patients. AB - The effect of Cavinton tablet has been examined in elderly diabetic patients. According to the observations the intellectual performance of the treated patients improved significantly, and their neurological symptoms were moderated as well. The drug did not influence carbohydrate or lipid metabolisms nor did it affect the systemic blood pressure. The results obtained prove that the drug may successfully be used for the treatment of nervous symptoms of elderly diabetic patients. The assure an effective therapy the drug administration has to be started as early as possible--before the development of nervous symptoms. The dosage of the product has to be adjusted individually. Obviously, the currently accepted other drug therapies of manifesting nervous symptoms have to be used as well and the other diseases accompanying advanced age need also be treated. PMID- 2588203 TI - Cellular characteristics of sputum from patients with asthma and chronic bronchitis. AB - The reproducibility of sputum cell counts was examined and the cell counts in patients with asthma were compared with those in patients with chronic bronchitis. Three groups of subjects were studied. Sputum from eight patients with chronic asthma and with sputum production were studied to determine the reproducibility of sputum cell counts. The findings in 10 non-smokers with asthma uncomplicated by other airway disease examined at the time of an exacerbation with sputum (group 2) were compared with those from eight smokers with chronic cough and sputum but no features of asthma (group 3). Sputum plugs were selected by microscopy to ensure their origin from the lower respiratory tract. A total cell count was performed on a trypsinised suspension, and differential and metachromatic cell counts were performed on undiluted plugs. The within specimen and test-retest reproducibility of these measurements was high (reliability coefficient, R, = 0.99 and 0.89). The sputum of the asthmatic patients was characterised by eosinophilia (69%, range 46-92%) and the presence of formaldehyde blockable metachromatic cells (1.5%, range 0.6-2.8%). In comparison, the sputum of the patients with chronic bronchitis had few eosinophils (0.5%) or metachromatic cells (0.14%); the dominant cell type was the macrophage (83%). It is concluded that sputum cell counts are reproducible in the short term, the inflammation of asthma is characterised by eosinophilia and metachromatic cells in sputum, and sputum may provide a useful source of cells for investigating the cellular characteristics of airway inflammation. PMID- 2588204 TI - Accident and emergency department attendance by asthmatic children. AB - Attendances at the accident and emergency department of a children's hospital for treatment of acute asthma were studied for one year to determine the characteristics of the children attending and their management. Eight hundred and twenty children, median age 5.5 years, made 1389 visits. Records were available from 1046 visits. Clinical information and assessment of the severity of the attack in the department was often inadequate. Peak flow records were available for 366 (35%). Attendances were most frequent in September and during the evening, but there was no significant day to day variation. Eight hundred and three children (78%) were self referred. Before attendance 962 (92%) had used a bronchodilator, including nebulised salbutamol (11%); 2% had taken prednisolone and 21% antibiotics. Five hundred and sixteen visits (49%) led to admission and 19% of those admitted required intravenous treatment. Probably some children who at present attend hospital for treatment of acute asthma could be managed at home, but this cannot be assumed without better understanding of the reasons for hospital attendance. More information is needed. PMID- 2588205 TI - Pressurised aerosol deposition in the human lung with and without an "open" spacer device. AB - A radiotracer technique has been used to assess aerosol delivery from a pressurised metered dose inhaler, used both with and without a 10 cm cylindrical spacer attachment (Syncroner), which has an open section in its upper surface. The radionuclide technetium-99m (99mTc) was added to sodium cromoglycate in a canister (Intal inhaler; 1 mg/puff); in vitro studies with a multistage liquid impinger showed that the radiolabel acted as a marker for the presence of drug over a wide range of particle sizes. Ten healthy volunteers were studied after they had inhaled from (1) a metered dose inhaler alone (slow inhaled flow rate, about 25 l/min); (2) metered dose inhaler plus spacer (slow flow rate); and (3) metered dose inhaler plus spacer (fast inhaled flow rate, about 100 l/min). Inhalation was coordinated with firing the spray and was followed by 10 seconds' breath holding. With the metered dose inhaler alone a mean 11.0% (SEM 1.4%) of the dose reached the lungs, compared with significantly higher doses for slow (16.1% (2.2%] and fast (13.3% (1.7%] inhalations through the spacer. The distribution pattern within the lungs was significantly more peripheral after slow inhalation. Oropharyngeal deposition was halved by the spacer. The open spacer should teach patients good coordination and delivers more aerosol to the lungs than a correctly used metered dose inhaler. PMID- 2588206 TI - Bronchiolitis obliterans organising pneumonia in patients taking acebutolol or amiodarone. AB - Two patients, treated with acebutolol and amiodarone respectively, developed a disease clinically, radiologically, and pathologically indistinguishable from bronchiolitis obliterans organising pneumonia. In one case recovery followed discontinuation of acebutolol; in the other case cessation of amiodarone had no effect, and corticosteroids were required. In addition to these patients, several cases of bronchiolitis obliterans organising pneumonia have been reported during treatment with gold salts, amiodarone, and miscellaneous other drugs. Taken together, this information supports the view that bronchiolitis obliterans organising pneumonia may be a form of response by the lungs to insult by drugs. PMID- 2588207 TI - Adverse effect of additional weight on exercise against gravity in patients with chronic obstructive airways disease. AB - The effects of an acute, artificially simulated increase in body weight on exercise performance were examined in 14 patients of normal weight (mean (SD) body mass index 22.3 (2.7)), age 61 (8) years) with chronic obstructive airways disease (FEV1 1.2 (0.5) 1; vital capacity (VC) 2.9 (0.6) 1), and in six normal subjects with similar age and sex distribution. The patients performed a six minute walking test and a symptom limited step climbing test both with and without an additional 10 kg weight (two leaded aprons). The normal subjects performed a step test with and without the additional weight. Ventilation (VE) and oxygen consumption (VO2) were measured during step climbing. Resting spirometric values were not altered by the additional weight. In the patients the median number of steps climbed fell from 67.5 when they were unweighted to 44.5 when they were weighted. Mean VE and VO2 were increased during weighted step climbing by 14% and 13% but the maximum levels of VE and VO2 achieved were similar during unweighted and weighted exercise (VE 36.8 (8.6) and 37.3 (10.2) 1 min-1, VO2 1.35 (0.3) and 1.41 (0.4) 1 min-1 respectively). The normal subjects were readily able to complete 150 steps both with and without the additional weight. In the patients the six minute walking distance fell only slightly with the extra weight, from 554 (SD 61) to 540 (62) m. A subsidiary study was carried out in six healthy younger subjects in which VE and VO2 were measured during a 5.6 km/h six minute treadmill walk at zero incline. The additional weight did not alter VE or VO2 during exercise. In conclusion, a small acute increase in body weight substantially worsened the already reduced "uphill" exercise performance in patients with chronic obstructive airways disease because of its effect on ventilation and oxygen consumption. These results suggest that modest weight loss might benefit patients with chronic obstructive airways disease even though they may be only slightly above their ideal body weight. PMID- 2588208 TI - Coronary artery bypass surgery: current practice in the United Kingdom. AB - A survey of current clinical practice was carried out among the 84 consultant cardiac surgeons currently performing coronary artery bypass surgery in the United Kingdom. The 80 surgeons who returned the questionnaire performed an estimated total of 17,100 coronary artery bypass graft operations in 1987, a mean case load of 214 operations each. Sixty two of the 80 surgeons regarded the internal mammary artery as the graft conduit of choice, and seven preferred the saphenous vein. The internal mammary artery was used in 73% of bypass grafts to the left anterior descending coronary artery but in only 4% of grafts to the circumflex and right coronary systems. Contraindications to the use of the internal mammary artery included advanced age of the patient (51 surgeons), insufficient flow through the internal mammary artery (49), and endarterectomy (35). Seventy four of the 80 surgeons considered intraoperative damage to the saphenous vein to be a possible cause of vein graft failure, but there was no agreement about how it should be reduced. All surgeons advocated pharmacological measures to enhance graft patency. Dipyridamole and aspirin constituted the most popular regimen (58 surgeons), though only 28 started dipyridamole preoperatively. Warfarin was prescribed postoperatively on occasion by 22 surgeons, but 14 of these used it only after endarterectomy. PMID- 2588209 TI - Decreased pulmonary distensibility in fibrosing alveolitis and its relation to decreased lung volume. AB - The relation between pulmonary distensibility, lung volume, and elastic recoil pressure was examined in 45 patients (38 men) with cryptogenic fibrosing alveolitis (mean age 61 (SD 14) years). Exponential analysis of static pressure volume data obtained during deflation of the lungs gave the exponent K, an index of the distensibility of the remaining inflatable lung tissue. Total lung capacity (TLC) was measured in a body plethysmograph or by nitrogen washout. The results were compared with values obtained in 147 healthy subjects (95 men), of mean age 39 (SD 16) years. Fibrosing alveolitis decreased K by 0.62 (SEM 0.04) kPa-1. This decrease was approximately equal to 2 SD of the regression of log K on age in healthy subjects. TLC was decreased to a mean of 70% (SD 14%) predicted in the patients with fibrosing alveolitis. Lung recoil pressure at maximum inspiration was about twice the expected value and regression analysis showed that most of this increase was related to the decreased K rather than to the decreased TLC. In the men with fibrosing alveolitis the regression of height standardised TLC (TLC/Ht3) on K was significant (p less than 0.02); the regression slope was similar to that for 95 healthy men, but was displaced to a smaller lung volume. The dependence of TLC/Ht3 on K is consistent with the close relation between K and peripheral airspace size found in normal lungs. In fibrosing alveolitis decreased pulmonary distensibility probably reflects a decrease in airspace size, whereas most of the decrease in lung volume reflects the loss of inflatable tissue in the fibrotic process. PMID- 2588212 TI - Effect of corticosteroids on post-intubation tracheal stenosis. AB - A 57 year old patient presented with progressive tracheal stenosis two months after intubation. An intraluminal polypoid lesion was found at the site of the cuff of the endotracheal tube. It disappeared within five days of treatment with inhaled beclomethasone. Further improvement of forced expiratory and inspiratory flow occurred after systemic corticosteroid treatment, with resolution of peritracheal oedema. Topical and systemic corticosteroids may be useful in the management of early post-intubation tracheal stenosis. PMID- 2588210 TI - Bronchoalveolar lavage cell counts as a predictor of short term outcome in pulmonary sarcoidosis. AB - Sixty seven patients with biopsy proven pulmonary sarcoidosis were prospectively studied to determine whether single point bronchoalveolar lavage cell counts were a useful indicator of functional outcome and whether repeated lavage helped in management. The mean follow up period was 25 (range 13-37) months. No patient was having corticosteroid treatment at the time of initial bronchoalveolar lavage. "High intensity alveolitis" (lymphocyte count greater than or equal to 28%) was present at the initial lavage in 42 patients. These patients showed a significant improvement in their pulmonary function and chest radiographs over the follow up period whereas patients with "low intensity alveolitis" did not. Of the 42 patients with high intensity alveolitis, 31 had chronic sarcoidosis (duration over two years, mean 80 months). These patients showed a significant improvement in FVC but not in TLCO. Corticosteroids resulted in greater functional and radiological improvement in the patients with high intensity alveolitis than in those with low intensity alveolitis. Repeat bronchoalveolar lavage in 34 patients, mean 8.4 months after the original lavage, showed a weak inverse relation between a reduced lymphocyte count and change in forced vital capacity and isotope uptake on a gallium scan. These correlations were too weak to make repeated cell counts useful in management. Our results suggest that high intensity alveolitis may be a favourable prognostic factor for lung function in pulmonary sarcoidosis, even in patients with chronic disease, but that repeat lavage adds little to the management of the individual patient. PMID- 2588211 TI - Infective respiratory exacerbations in young adults with cystic fibrosis: role of viruses and atypical microorganisms. AB - Thirty six adults with cystic fibrosis were studied over one year to determine the incidence of infection with respiratory viruses and atypical organisms. Nineteen patients entered the study during an acute exacerbation of respiratory symptoms with an increase in purulent sputum production, cough, or breathlessness accompanied by a fall in FEV1 (group 1); 17 patients entered when they were stable both clinically and in terms of lung function values (group 2). Group 1 patients had a mean of 2.6 (range 1-4) infective exacerbations during the year and group 2 patients a mean of 1.1 (0-2) exacerbations. Eleven patients developed serological evidence of viral (influenza virus A and B, cytomegalovirus, human rhinovirus 2, adenovirus) or Mycoplasma pneumoniae infection. There was no difference in seroconversion rates between group 1 (five patients) and group 2 (six patients). There was a weak association between viral seroconversion and the isolation of Pseudomonas aeruginosa from sputum, though this was not significant. PMID- 2588213 TI - Annular lesion of the lung in sarcoidosis. AB - A 20 year old man presented with eight thin walled, ring shaped shadows, 1-3 cm in diameter, on a chest radiograph. Pulmonary sarcoidosis was diagnosed on the basis of histopathological examination of a cervical lymph node, transbronchial lung biopsy, and increased activity of angiotensin converting enzyme and lysozyme in serum. The lesions disappeared within six months of his starting corticosteroid treatment. PMID- 2588214 TI - Heterozygous FZ alpha 1 antitrypsin deficiency associated with severe emphysema and hepatic disease: case report and family study. AB - A patient with advanced emphysema and cor pulmonale had the changes of alpha 1 antitrypsin deficiency in a liver biopsy specimen and was shown to have the phenotype PiFZ. This case supports the contention that the F allele of alpha 1 antitrypsin predisposes to the development of emphysema, particularly when it occurs in conjunction with the Z allele. PMID- 2588215 TI - Pseudo-occupational asthma. AB - A case is reported in which a pattern of work related asthma in a record of peak expiratory flow was artefactual. The patient had pronounced morning dips, which she recorded on working days, when she made the first recording at 0700 h, but not on holiday, when she stayed in bed longer. The case emphasises the need for clear instructions to patients about peak flow records. PMID- 2588216 TI - Colopleural fistula due to strangulated Bochdalek hernia in an adult. AB - An elderly patient presented with a right sided pneumothorax due to strangulation of part of the colon through a congenital Bochdalek hernia. Congenital posterolateral diaphragmatic hernia of Bochdalek is rare in an adult and strangulation with pneumothorax has not been reported before. PMID- 2588218 TI - Minitracheotomy: a simple alternative to tracheostomy in obstructive sleep apnoea. PMID- 2588217 TI - Attitudes to smoking and smoking habit among the staff of a hospital. PMID- 2588219 TI - Alveolitis associated with sulphamethoxypyridazine. PMID- 2588221 TI - [Anxiety, diagnosis and reliability]. PMID- 2588222 TI - [Measles]. PMID- 2588220 TI - [Prenatal care in focus]. PMID- 2588223 TI - [Psychiatric diagnoses in self-help groups of the "Only Anxiety" society in Bergen]. AB - 45 members of self-help groups for persons with anxiety disorders were interviewed using Structured Clinical Interview of DSM-III-R. 21 interviews were video-recorded and rated by an independent rater. Panic disorder was the most common diagnosis, together with present or past serious depression. We discuss the relation between anxiety disorders and affective disorders. Interrater agreement was high for panic disorder, but not for the diagnoses generalized anxiety disorder and simple phobia. Questions are raised about the clinical validity of generalized anxiety disorder. PMID- 2588224 TI - [Measles in Norway. Epidemiology before and after the introduction of routine vaccination]. AB - Twenty years after routine vaccination against measles was introduced in Norway its incidence has been reduced by over 97%. Measles encephalitis has not been reported in Norway since 1982 and the last registered death from the disease was in 1985. There is evidence of a certain increase in the age of measles patients since the introduction of vaccination but this has not led to any increase in the death-to-case ratio. The vaccines (measles vaccine from 1969 and MMR from 1983) have proved safe in use, with few reported probable or possible reactions. The vaccination programme has resulted in a large reduction in measles morbidity but if the goal of eradicating endemic measles in Norway by 1990 is to be achieved, then coverage must be further improved. PMID- 2588225 TI - [Measles in Norway. The first 6 months of 1988]. AB - The incidence rate of measles in Norway in the first six months of 1988 was 2.6 per 100,000. This is the lowest half-yearly incidence rate registered in Norway, but because of a change in the method of reporting the figures are not directly comparable. There was an epidemic in Norway's northernmost county (Finnmark) and an outbreak in an army camp in the county of Troms (also in the north). On a national basis 48% of the cases were preventable, but there were considerable local variations. In Finnmark 77% of cases were preventable. No serious complications (death or encephalitis) were registered but the rate of other complications was higher than expected. There was an even distribution of cases in the different age-groups up to 15 years, but there were considerable local variations. Despite the low incidence rate there is much that suggests that immunization coverage is still low in some areas. If the goal of eliminating indigenous measles by 1990 is to be achieved then urgent action is required to improve immunization coverage. Intensification of preventive measures around individual cases is also necessary. Suggestions for measures to further reduce the incidence rate of measles in Norway are included in the conclusions to the article. PMID- 2588226 TI - [Treatment of fibromyalgia by low-frequency transcutaneous nerve stimulation]. AB - Fibromyalgia is a syndrome of a non-inflammatory nature characterized first and foremost by great pain in a number of tendons and muscles. The syndrome has only recently been delineated as a separate entity, the criteria for which are still being discussed. Recent studies have revealed reduced oxygenation in the trigger points, apparently a result of reduced microcirculation due to sympatho inhibition (5). Since low-frequency TNS is known to increase microcirculation in skin and muscles in widespread areas, and since such stimulation also produces widespread pain-relief through the activation of endogenous opioids, this appears to be a rational therapy for this syndrome. In the present study, 40 patients with fibromyalgia received low-frequency TNS. The effects were beneficial in about 70% of the cases. PMID- 2588227 TI - [Gastrointestinal myoelectric activity]. AB - Gut motility research is a field where rapid progress is being made. We expect that, in future, diagnosis and treatment of motility disorders will become an important part of gastroenterology. Various techniques are now available for studying motility. This paper reviews one of them, namely recording and interpreting gastrointestinal myoelectric activity. PMID- 2588228 TI - [Medical expert systems. What are they and how should we organize our efforts?]. AB - Medical expert systems have been developed for more than 20 years, in particular in the United States. Most existing systems are prototypes, and only a few commercial systems are available. The prototypes are generally limited in scope or functions (and have not been transferred to other users). However, in the near future we can expect useful applications to appear in special areas of medicine. In Norway we probably do not have the resources required to develop large commercial medical expert systems. If we want to develop medical expert systems, we should concentrate on limited areas. We must prepare the ground for future use of such systems in Norway. An important first step is to give health personnel basic education in the use of computers. PMID- 2588229 TI - [Genetic variation and genetic diseases]. AB - Detailed knowledge of the genetic make-up of individuals, revealed by examination of their DNA, is emerging as a significant component in medical diagnosis. Sometimes direct examination of DNA can determine whether a mutant gene is present or not. In other instances the genetic constitution of an individual can be inferred by use of genetic markers known to be close to the gene. The applications of this new level of knowledge are far reaching, extending to disease predisposition to several illness and responses to infectious agents. The use of DNA polymorphisms associated with linked DNA segments should permit diagnosis of hitherto undetectable disease states and also chromosomal localization of the loci responsible. The eventual isolation of the gene itself should lead to a better understanding of the molecular basis of inherited disease. PMID- 2588230 TI - [Genetics and coronary heart disease]. AB - The article reviews some of the evidence that genetic factors are important in the etiology of coronary heart disease (CHD). Having a first degree relative with CHD at a relatively young age is in itself a risk factor that may not be reflected in increased lipid levels. Several genetic polymorphisms are associated with risk factor level and/or CHD, and genes have a significant effect on the level of several risk or "anti-risk" factors. Lp(a) lipoprotein, which exhibits a definite association with CHD, is under strict genetic control. A high level of Lp(a) lipoprotein does not in itself result in increased lipid levels, and it is therefore necessary to conduct specific tests with regard to this important genetic risk factor. DNA variation at several apolipoprotein loci has been examined and several associations with risk factor levels have been reported. Present knowledge of genetic predisposition to CHD should be utilized in predictive genetic testing to prevent disease, preferably within a framework of family-oriented preventive medicine. PMID- 2588231 TI - [Gynecomastia. Investigation and surgical treatment]. AB - Enlargement of the male breast, gynecomastia, commonly occurs in otherwise healthy men. If the gynecomastia is marked, surgical treatment may be necessary. Underlying disease must be considered. History, physical examination, laboratory tests and in some patients ultrasonography of the testes should be conducted prior to surgery. If the gynecomastia is due mainly due to fat, suction lipectomy alone is sufficient treatment. However, liposuction will not remove breast parenchyma, and some patients also require local excision of the parenchyma. In our experience, suction lipectomy provides a new means of acquiring better contour, with reduced morbidity and complications. PMID- 2588232 TI - [A model for organization of prenatal care]. AB - The article presents a model for organized prenatal care in a district of 45,000 people. General practitioners, midwives and an obstetrician share responsibility for pregnant women in the region. The general practitioners have primary responsibility for the prenatal care, but all the pregnant women are offered consultation with the midwife twice and with the obstetrician once during the pregnancy. The midwives give general information on pregnancy and birth, and also take part in the ultrasonographic screening program. The obstetrician provides individual care to women with risk pregnancies, or in the event of complications. This system offers similar prenatal care to all pregnant women in the area without interfering with their personal wishes. PMID- 2588233 TI - [Sick-listing of pregnant women. A survey and evaluation]. PMID- 2588234 TI - [HIV screening of pregnant women and women seeking abortion. A preventive measure against HIV?]. AB - In our opinion, screening of women seeking abortion and pregnant women does not benefit the work of HIV-prevention. Of the 115,600 tested from September 1987 to December 1988 in Norway, four new and HIV-positive and 92 false positive women were diagnosed. From the time screening started in September 1987 to the end of February 1989, the program has cost NOK 6-7 million. The prevalence of HIV among pregnant and abortion-seeking women is too low, and the problems associated with false positive results are too great for the project to be recommended. Pregnant women and women seeking abortion, and their partners, should be given the possibility of taking the HIV-test in the same manner as other low prevalence groups, where information and counselling are integrated and confidentiality is secured. PMID- 2588235 TI - [Duration of and ending of the stay in the puerperal ward]. PMID- 2588236 TI - [Fibromyalgia]. PMID- 2588237 TI - [Ultraviolet radiation and eye injuries]. PMID- 2588238 TI - [Neonatal hemolytic icterus in foals. A study of antibodies in colostrum and serum]. AB - Investigations for the presence of antibodies to red blood cell antigens were carried out in equine colostrum and serum. Material from 181 mares without clinical disease was tested. The object was to obtain information on the number of mares producing antibodies capable of inducing haemolytic disease in newborn foals. Of the mares 2.8% was positive for haemolysins. These mares are expected to be a risk for haemolytic disease. In addition agglutinating antibodies were identified in 39.2 per cent of the mares examined. It is not known whether or not these antibodies constitute a hazard for the foals. A smaller group of sera from mares was analysed to verify or disprove the diagnosis of haemolytic disease. Some of these mares showed very high haemolysin titres. Several cases are reported in greater detail. It is clear that the information obtained from these cases shows that haemolytic disease of newborn foals also occurs after the first pregnancy of mares. PMID- 2588239 TI - [The optimal service period in bitches]. AB - The fertile period in bitches as estimated from the findings reported in the literature is discussed. Fertile periods of oocytes and spermatozoa are examined extensively. The period of ovulation is found to be more closely associated with hormonal changes than it is with symptoms of oestrus. This period occurs when the concentration of progesterone in the blood increases to a level higher than (16 nmol/l). Service one and a half days after the ovulation period results in high pregnancy rates. PMID- 2588241 TI - [Measles still an important problem in the Third World. Model study with chicks shows vitamin A deficiency very harmful]. PMID- 2588240 TI - [Acute poisoning in animals in The netherlands in the period 1985-1988]. AB - The National Poison Control Centre (NVIC), a unit of the National Institute of Public Health and Environmental Hygiene, the Netherlands, provides a 24-hour service to inform physicians, veterinary surgeons, dentists and pharmacists in case of poisoning. The total number of requests was 20,514 in 1988. In the period from 1985 to 1988 from 3 to 4 per cent of the cases in which information was supplied, concerned suspected cases of acute poisoning in animals. Pesticides were involved in the majority of cases, particularly in dogs, cats, cattle and sheep. As a result of exposure to household 'do-it-yourself' products, in dogs and cats, 40 per cent of these cases were caused by mineral oil products, such as petrol, turpentines, motor oil and lamp oil. Cases of poisoning by plants occur particularly in sheep and goats. In 50 per cent of the fatal cases the poisoning was caused by pesticides, in 17 per cent of the cases it was due to plants, in 0.5 per cent of the cases to human drugs and 0.1 per cent of the cases to veterinary drugs. PMID- 2588242 TI - [Cesarean section]. PMID- 2588243 TI - Repetitive intercostal nerve block via catheter for postoperative pain relief after thoracotomy. AB - After anterolateral thoracotomy, before incision closure, indwelling plastic catheters were inserted percutaneously under digital and/or visual control into the intercostal space of access and the two neighbouring ones. Initially, we injected 25 mg of bupivacaine through each catheter (to a total of 75 mg), and subsequently - on the patients demand - another 15 to 25 mg per catheter. To date, 25 patients received repetitive intercostal nerve blocks by this method (ICB-group). We compared their personal and perioperative data with those of another 30 patients, receiving opiates systemically after major thoracic surgery (SA-group). Multiple blood samples from the ICB-group were analyzed by gaschromatography for bupivacaine concentration-time-profiles. In 19 of 25 patients (76%) the bupivacaine-injections provided sufficient analgesia, 6 patients required additional analgesics. The duration of general anaesthesia (ICB: 174 min vs. SA: 136 min) and the operation time (ICB: 103 min vs. SA: 94 min) were not statistically different in both groups. The periods of intensive care therapy (ICB: 0.7 d vs. SA: 1.2 d), artificial respiration (ICB: 11.2 h vs. SA: 21.6 h) and hospital stay (ICB: 12.1 d vs. SA: 14.2 d) were shorter for the ICB-group. Atelectasis (ICB: 20% vs. SA: 37%) and pneumonia (ICB: 0 vs. SA: 13%) were observed less frequently than in the control group, whereas tachyarrhythmia occurred in 6 of 25 ICB-patients compared to 4 of 30 SA-patients. Nevertheless, none of these parameters reached statistical significance (p less than 0.05). Maximum bupivacaine levels of 0.65 +/- 0.21 micrograms/ml were found after 29 +/- 12 min of intercostal application.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588244 TI - Mucociliary clearance following tracheal resection and end-to-end anastomosis. AB - Mucociliary clearance is an important cleaning system of the bronchial tree. The complex transport system reacts sensitively to medicinal stimuli and inhaled substances. A disturbance causes secretion retention which encourages the development of acute and chronic pulmonary diseases. It is not yet known in which way sectional resection of the central airway effects mucociliary clearance. A large number of the surgical failures are attributable to septic complications in the area of the anastomosis. In order to study the transportation process over the anastomosis, ten dogs underwent a tracheal resection with end-to-end anastomosis, and the mucociliary activity was recorded using a bronchoscopic video-technical method. Recommencement of mucous transport was observed on the third, and transport over the anastomosis from the sixth to tenth, postoperative days. The mucociliary clearance had completely recovered on the twenty-first day in the majority of dogs. Histological examination of the anastomoses nine months postoperatively showed a flat substitute epithelium without cilia-bearing cells in all dogs. This contrasts with the quick restitution of the transport function. In case of undamaged respiratory mucosa, a good adaptation of the resection margins suffices for the mucous film to slide over the anastomosis. PMID- 2588245 TI - A contribution on the prognostic significance of the tumor formula (pTNM) in squamous cell carcinoma of the bronchus. AB - Analysable data on survival time could be obtained in the context of a follow-up investigation for 435 of 518 patients who had been operated on for squamous-cell carcinoma of the bronchus in the period 1976 to 1986. For better comparison, all tumors were staged retrospectively according to the fourth edition (1987) TNM schedule of the UICC. The mean survival time after potentially curative operation was 7.15 years in stage I, the five-year actuarial survival was 60.8%. The corresponding values were 2.68 years and 31.6% respectively in stage II, compared to 1.14 years and 13.4% respectively in stage IIIa. The differences between tumor stages are statistically significant. The nature of the resection treatment within the tumor stages did not have any effect on the survival times. Tendency to keratinize, lymphangiosis carcinomatosa, and infiltration of tumor cells into vessels also had no prognostic significance. It was also analysed to what degree tumor size and extent as well as lymph-node involvement influence the prognosis after potentially curative operation. In the absence of lymph-node involvement, the prognosis of patients with T1 and T2 tumors was significantly better than that of patients with T3 tumors. However, when metastatic spreading into bronchopulmonary lymph nodes was present (N1), the prognoses of patients with T1, T2 and T3 tumors no longer differed significantly from each other. In mediastinal lymph-node involvement (N2) and T1 tumor, the survival times were significantly better than in mediastinal lymph-node involvement and T2 or T3 tumor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588246 TI - Jamming of prosthetic heart valves by suture trapping: experimental findings. AB - The vulnerability of the Medtronic-Hall, Bjork-Shiley Monostrut, Duromedics, and St. Jude Medical valves to occluder immobilization by sutures was determined under static and pulsatile flow conditions. Variables were cardiac output, cross sectional diameter of suture, type of suture (braided versus monofilament) and position of the offending suture along the circumference of the valve ring. Under static conditions, pressures, ranging from 40 to 340 mmHg and 10 to 170 mmHg, were required to decompress obstructed Medtronic-Hall and Bjork-Shiley Monostrut valves, respectively. As a result of different design characteristics and different occluder/orifice clearances the Medtronic-Hall valve showed its maximum opening pressure in case of interference with sutures at the axis of symmetry in both minor and major orifices, whereas for the Bjork-Shiley Monostrut valve this was reached in the minor orifice. Under pulsatile flow conditions, in case of interference with Prolene 2-0 suture, the Duromedics valve showed irregularly delayed opening and an opening pressure difference of 50 mmHg at a cardiac output of 8 L/min, whereas leaflet motion and pressure difference in the St. Jude Medical valve were undisturbed under similar conditions. The necessary pressure difference for opening the Medtronic Hall valve reached 44mmHg at a cardiac output of 8 L/min. High and low risk of extrinsic leaflet obstruction in the Duromedics and St. Jude Medical valves, respectively, is related to the design of the hinge mechanisms and the wedge angle of their leaflets (2 degrees versus 25 degrees). Precautionary principles in implantation of prosthetic heart valves are stressed to prevent the potentially lethal complication of occluder immobilization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588247 TI - The complex posterior septal space in the Wolff-Parkinson-White syndrome. Surgical experience with 47 patients. AB - Forty-seven consecutive patients with the Wolff-Parkinson-White syndrome due to posterior septal accessory pathways were operated on from August 3, 1983 to March 23, 1989. Seven of these patients had Ebstein's anomaly, another three coronary sinus aneurysms, one a persistent left superior vena cava, and five others complex multiple pathway combinations. Two additional patients required surgery following unsuccessful catheter ablation and one after failed surgery at another institution. Thus nineteen of forty-seven patients (40%) had additional difficulty factors which tend to complicate the operative dissection in this already complex anatomical area. The surgical anatomy of the posterior septal space as well as the essential operative principles and techniques are reviewed. Each of the frequently encountered additional difficulty factors is described with emphasis on the coronary sinus aneurysm, a recently recognized entity. PMID- 2588248 TI - The use of the internal mammary artery for myocardial revascularisation in patients 70 years of age and older. Does it complicate the early post-operative period? AB - In the last years common agreement has been reached that the internal mammary artery (IMA) is the conduit of choice for elective myocardial revasculariation. This trend has been stimulated by the long-term patency of the IMA grafts and the better long-term survival. However, with the increase in life-expectancy, an increasing number of elderly patients is referred for coronary artery bypass grafting. In this patient population the long-term survival is generally limited, and therefore many surgeons do not use the IMA as graft. However, there is not only the better long-term survival but also a reduction in recurrence of angina, cardiac events, and need for reoperations associated with the IMA use. In this study the perioperative (peroperative and early postoperative) mortality and morbidity of coronary artery surgery with IMA use and without IMA use in patients aged 70 years and older is compared. Based on the early clinical results it is suggested that the use of an IMA graft does not influence the perioperative morbidity and mortality of coronary artery surgery in the patient over 70, who thus should not be denied the conduit of choice on such grounds. PMID- 2588249 TI - Will emergency coronary bypass grafting after failed elective percutaneous transluminal coronary angioplasty prevent myocardial infarction? AB - An emergency aorto-coronary bypass grafting operation was performed within 12 hours after the development of acute myocardial ischemia due to partial or complete vascular occlusion in 34 of 950 (3.6%) patients who had received elective percutaneous transluminal coronary angioplasty (PTCA). Of the 34 patients, three (= 8.8%) died postoperatively in irreversible cardiogenic shock. Half of the surviving patients developed a Q-wave infarction after the operation, whereas the other half remained without transmural infarct. With comparable clinical data and times of operation up to placement of the aorto-coronary bypass vessel, an adequate residual perfusion must still have been present in the cases with non Q-wave infarction. Since in many cases a myocardial necrosis is unavoidable despite relatively early operative revascularization, the decisive role will be played by the remaining perfusion of the vessel concerned and any collaterals. It follows that treatment of an early PTCA complication, occurring in the catheter laboratory, ought to be the earliest possible aorto-coronary bypass operation unless available cardiological methods can reliably assure reperfusion. Treatment of a PTCA complication occurring later, however, e.g. after hours in the intensive-care unit, should be a repeat PTCA attempt: surgery at this stage will not prevent the transmural infarction but will increase risk of lethal complications. PMID- 2588250 TI - A "semi-supported" porcine xenograft--description and first clinical use. AB - The anatomy of valsalva's sinus is such that it decreases the mechanical stress on the leaflets of the aortic valve. Artificial stents impair the hemodynamic performance of an aortic bioprosthesis and lead to unphysiological functional stresses and may also shorten their durability. Therefore a semi-supported xenograft was developed which can be attached with an one-suture row in subcoronary position. This facilitates surgery considerably. Moreover, the commissures can be attached directly to the patient's aortic wall. The semi supported valve was successfully implanted in a 69 years old patient with a combined aortic valve lesion. Postoperative invasive investigations, including angiography and videodensitometry, showed a normal performance of the valve and a normal anatomy of the aortic root. PMID- 2588251 TI - Multiple cutaneous myxomas coinciding with repeated cardiac myxomas. A syndrome. AB - We report on a 31-year-old woman who underwent surgery for two metachronous cardiac myxomas - 7 and 9 years after excision of several cutaneous myxomas. Our observation is a further case of a syndrome-like complex of cardiac and cutaneous myxoma(s), pigmentation anomalies and endocrine disorders described only recently. As modern investigative methods and the development of cardiovascular surgery have brought about an essential improvement in diagnostics and prognosis of cardiac myxomas, the knowledge of this syndrome-like complex is of great therapeutic importance. Therefore, in our opinion, echocardiographic investigations are strongly recommended even in asymptomatic patients, once several cutaneous myxomas are diagnosed histologically. PMID- 2588252 TI - Fatal progression of Behcet's disease after cardiac surgery. AB - The authors describe a patient affected with Behcet's disease who developed, after cardiac surgery, acute clinical manifestations of the syndrome and died of a generalized infection. They also discuss the clinical aspects, the particular clinical course, and the therapy of the disease. PMID- 2588254 TI - Spontaneous coronary artery dissection with left ventricular aneurysm--a case report of successful surgical repair. AB - An aorto-coronary artery bypass operation combined with left ventricular aneurysmectomy was performed successfully in a 56-year-old man who had suffered spontaneous coronary artery dissection with left ventricular aneurysm. It is important to perform myocardial revascularization surgery even if the region for anastomosis is dissected. PMID- 2588253 TI - False aneurysm secondary to aortic cannulation--rupture into lung with fatal hemoptysis during aortography. AB - We report a case of fatal rupture of a false aneurysm of the ascending aorta during aortographic injection. The aneurysm had formed at the site of aortic cannulation done for a cardiac bypass at an earlier date. The rupture manifested as hemoptysis as the false aneurysm had burrowed and ruptured into the anterior segment of the right upper lobe of the lung. PMID- 2588255 TI - Postoperative subphrenic abscess after heart-valve replacement. AB - A 35 year-old male patient developed a subphrenic abscess in the immediate postoperative period after replacement of a calcified mitral bovine pericardium bioprosthesis. He was successfully treated with abdominal percutaneous drainage and antimicrobial therapy. PMID- 2588256 TI - Delayed isolated mitral incompetence after being kicked in the chest by a bull. AB - Isolated mitral valve incompetence after blunt chest trauma is rare. A case report is presented. Incidence of isolated mitral incompetence and combined heart injuries, valve damage mechanics, and frequent causes of blunt chest trauma are discussed. Immediate and delayed symptoms and several means to diagnose mitral valve incompetence are compared. Typical pathologic findings in mitral valve incompetence after blunt chest trauma are cited and therapeutic measures discussed. PMID- 2588257 TI - Survival after heart and coronary-artery penetration by an air-rifle projectile. AB - Gunshot injuries of the heart are extremely rare thoracic traumas in Europe during peacetime. Concomitant lesions of the coronary arteries occur in less than 5%. This case reports on a 26-year-old man who was shot with an air rifle at short range. On admission the patient showed signs of pericardial tamponade. Emergency thoracotomy was performed and a frontal cardiac lesion was found in the distal third of the anterior descending branch of the left coronary artery. The bullet crossed the cavum of the left ventricle and remained in the posterior wall in the subepicardial layer adjacent to the posterior descending coronary branch. Under the conditions of extracorporeal circulation we removed the bullet, repaired both ventricle walls using patches in sandwich technique, and bypassed the coronary lesion by single aortocoronary venous graft. No signs of myocardial infarction could be detected by ECG. The follow-up after 3 years shows no cardiac problems and normal stress tolerance. This case report proves that even air rifle shots, which in general are considered to be harmless, may result in life threatening injuries. For the severity of the injury are decisive the kinetic energy at the muzzle as well as configuration and type of the bullet. PMID- 2588258 TI - Mitochondrial function of isolated rat hepatocytes from normal and cirrhotic liver. AB - Mitochondrial fractions were obtained from purely isolated hepatocytes of the normal and cirrhotic livers. Mitochondrial function of isolated hepatocytes was evaluated to compare between those from the normal and those from the cirrhotic livers in addition to the evaluation of the mitochondrial function of the normal and cirrhotic liver tissues. Respiratory control, ADP/O ratio and ATP synthesis were significantly lower in the cirrhotic liver tissue than those in the normal liver tissue. However, the mitochondrial function of isolated hepatocytes showed no difference between normal and cirrhotic groups. By electron microscopic examination, debris was more observed in the mitochondrial fractions from the normal and cirrhotic tissues compared to those from hepatocytes. However, no difference of the shape and size of the mitochondria was seen between the fraction from hepatocytes and that from the tissue in each group. These results suggest that as far as hepatocyte itself is concerned, the cirrhotic liver preserves the sufficient function as well as the normal liver. PMID- 2588259 TI - Relationship of blood pressure to sodium and potassium excretion in Japanese women. AB - The cross-sectional association of blood pressure with urinary sodium and potassium excretion was investigated with a stepwise regression analysis. Spot urine of 7441 females between 40 and 69 years was collected from 169 municipalities (88 urban and 81 rural) covering all prefectures in Japan. The filter paper sampling technique for urine was used to collect samples of subjects from March to December in 1985. Spot urine samples were analyzed for sodium, potassium and creatinine. In addition, 24-hr sodium and potassium excretions were estimated by predictive equations. Blood pressure, sodium excretion and sodium potassium ratios were higher in rural areas than in urban areas. Consistent positive correlations between urinary sodium and blood pressure, and negative correlations between urinary potassium and blood pressure were observed in the whole country of Japan, in both urban and rural areas, and also in separate observations of twelve regions in Japan with some exceptions. When compared in standardized partial regression coefficients, relative effects of potassium on systolic blood pressure were higher than those of sodium in the whole of Japan, in urban and rural areas, and in five among the twelve regions. The present Japanese study confirmed a positive within-population relationship between sodium excretion and blood pressure and a negative relationship between potassium excretion and blood pressure. PMID- 2588260 TI - The role of amino acids and their transport systems in the regulation of ureogenesis in the primary culture of adult rat hepatocytes. AB - The biosynthesis of urea, the metabolism of ammonia and the transport of amino acids were studied using the primary culture of hepatocytes from adult rats. The urea synthesis and ammonia detoxication were affected by the amino acids of urea cycle intermediates, such as ornithine, arginine and aspartate. When the hepatocytes were incubated in the medium containing 1 mM ammonium chloride, the transport activity of system-A, which was determined by the uptake of specific substrate methyl-2-amino isobutyric acid (MeAIB), did not change compared with the control level. However, the transport activity of ornithine was increased to a maximum after 4 hr of incubation with ammonia, and then decreased gradually to twice the control level. The activity of ornithine transcarbamylase (OTC) increased to twice the control. These results indicated that the amino acids of urea cycle intermediates, especially ornithine, can be the important regulators of ureogenesis. PMID- 2588261 TI - Neonatal hyperammonemia associated with carnitine deficiency. AB - We report a case of neonatal hyperammonemia associated with secondary carnitine deficiency. She suffered from hyperammonemia soon after the birth, and then presented severe metabolic acidosis at 2 months of age. She was successfully treated for acidosis with oral administration of L-carnitine (100 mg/kg/day). Since hyperammonemia recurred with the increase of protein intake, it was necessary to increase the dose of carnitine to 150 mg/kg/day. Urea cycle enzymopathies were excluded from the laboratory data. The urinary organic acid profiled by gas chromatography mass spectrometry revealed no abnormalities. It was found that the carnitine contents in serum urine and muscle were decreased. After we investigated the carnitine status in other members of the family, the brother of this patient, who had died of metabolic acidosis and hyperammonemia of unknown etiology in the neonatal period, was also revealed to have carnitine deficiency. Since specific enzyme defects which caused secondary carnitine deficiency could not be detected in our patients, further biochemical characterization would be necessary to clarify the cause of hyperammonemia. PMID- 2588262 TI - Enhanced accumulation of hyaluronate in the culture of skin fibroblasts from two patients with Coffin-Lowry syndrome. AB - Cultured skin fibroblasts were prepared from two unrelated adult patients with full expressions of Coffin-Lowry syndrome. Glycosaminoglycans (GAGs) were isolated either from the medium or from the cell layer of cultured skin fibroblasts. Two-dimensional electrophoresis of GAG preparations on cellulose acetate film revealed that hyaluronate was the major component both in the medium and in the cell layer. Quantitative analysis of GAGs was carried out by measuring optical density at 615 nm of Alcian blue-stained GAG spots on electrophoretograms. Increase in the hyaluronate content was found both in the culture medium and in the cell layer of Coffin-Lowry fibroblasts. In addition, the incorporation of [14C]glucosamine into hyaluronate was similarly activated in skin fibroblasts from patients, suggesting the active biosynthesis and or the suppressed degradation of hyaluronate by cultured skin fibroblasts from Coffin Lowry syndrome. The abnormal metabolism of hyaluronate in Coffin-Lowry fibroblasts may be implicated in some of the clinical aspects of this genetic disorder. PMID- 2588263 TI - Tissue distribution of Pb in adult vs. old rats: a pilot study. AB - The coupling between the degenerative processes of aging and toxicant exposure has received little experimental attention. This experiment compared the tissue lead (Pb) distribution of adult and old rats exposed to 50 ppm Pb acetate in drinking water for 11 months and fed a semipurified diet. Blood Pb and zinc protoporphyrin (ZPP) determinations were carried out after 6 months of exposure; after 11 months of exposure blood lead and tissue Pb levels were determined. Several age-related differences between adult and old rats were noted: old rats exposed to Pb exhibited lower brain weights than old controls, a difference not noted between adult-control and adult-Pb rats. Pb-induced elevations of ZPP were confined to old-Pb rats while adult-Pb rats showed no increase relative to adult controls. Blood lead values of adult-Pb and old-Pb rats showed differential trends over the course of exposure: adult values declined, while those of old rats tended to increase further. Brain lead concentrations, and to a marginally significant extent, liver Pb levels, rose higher in old-Pb rats than in adult-Pb rats, while bone Pb levels were significantly less than those of adult-Pb rats. The current findings confirm the assertion that tissue Pb distribution patterns may be markedly altered when Pb exposure occurs during the later stages of the life cycle. PMID- 2588264 TI - A comparison of the effects of tetraplatin and cisplatin on renal function and gentamicin pharmacology in rats. AB - Tetraplatin (tetrachloro[d,l-trans]1,2-diaminocyclohexane platinum IV (TTP)) is a new platinum analogue active against L1210 murine leukemia that is resistant to cisplatin (diamminedichloroplatinum II (DDP)). Since nephrotoxicity is a significant problem with DDP therapy, we compared the effects of equitherapeutic doses of TTP and DDP on renal structure and function in rats. We also studied the effects of the 2 platinum compounds on the distribution and excretion of gentamicin (GENT), an antibiotic that is excreted solely by the kidneys. Rats treated intravenously with 2.85 mg/kg of DDP on days 1, 5 and 9 had significantly different plasma urea nitrogen (BUN) levels and creatinine clearance rates on day 16 than those given the same doses of TTP. The renal function of TTP-treated rats did not differ from that of controls or rats given only GENT. Twenty-four hours after a single GENT dose (given on day 15), DDP-treated rats had higher GENT concentrations in the plasma, liver and spleen than rats given GENT alone. TTP treated rats had higher GENT levels only in the spleen. DDP-treated rats retained a higher percentage of the injected platinum in the renal cortex than those treated with TTP. Light microscopic examination of renal tissue showed necrotic cells and dilated tubules in the proximal tubules of DDP-treated rats while the kidneys of TTP-treated rats were largely indistinguishable from those of controls. Thus, our results indicate that the distribution of platinum in the kidneys differs between rats treated with TTP and those treated with DDP. This may partly explain the considerably lower nephrotoxicity of TTP. PMID- 2588265 TI - Alteration of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by estradiol and tamoxifen. AB - We have hypothesized that part of the toxicity of 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) is mediated by interaction with the estrogen receptor complex. The experiments reported here investigate the interactions of TCDD with agonists and antagonists of the estrogen receptor. CD-1 female mice were observed for 2 months after treatment with various combinations of corn oil, estradiol, or tamoxifen, and/or TCDD in corn oil on 3 consecutive days. Estradiol had little effect on acute TCDD lethality but increased severity of TCDD-induced ascites and antagonized TCDD-induced uterine suppression. Severe liver damage did occur in TCDD and estradiol:TCDD treatment groups. Tamoxifen, a competitive inhibitor and a mixed agonist of the mouse estrogen receptor, antagonized the estrogenic effects of estradiol and estradiol:TCDD. Tamoxifen or tamoxifen:TCDD treatment greatly slowed body weight gain in comparison to controls and estrogen-treated animals. While the dose of tamoxifen used was otherwise non-toxic, tamoxifen greatly increased toxicity of TCDD as measured by time to death and percent lethality while having no effect on relative liver weight or relative uterine weight changes induced by TCDD. These findings are consistent with the hypothesis that a portion of the toxicity of TCDD is manifest through activity of the estrogen receptor complex. PMID- 2588266 TI - Investigations on organ-specific metabolism and genotoxic effects of the urinary bladder carcinogen N-nitrosobutyl-3-carboxypropylamine (BCPN) and its analogs N nitrosodibutylamine (NDBA) and N-nitrosobutyl-4-hydroxybutylamine (4-OH-NDBA). AB - N-Nitrosodibutylamine (NDBA) and its omega-oxidized metabolites N-nitrosobutyl-4 hydroxybutylamine (4-OH-NDBA) and N-nitrosobutyl-3-carboxypropylamine (BCPN) are potent urinary bladder carcinogens. To study putative organ specific activation of BCPN, its alpha-oxidation by liver and urinary bladder microsomal fractions was investigated in comparison to NDBA and 4-OH-NDBA. Additionally, induction of DNA single strand breaks (SSB) was monitored in hepatocytes and in a human lymphoblastoid cell line (Namalva) in the presence and absence of external metabolic activation, including N-nitroso-t-butyl-n-butylamine as a negative control. BCPN was alpha-hydroxylated and dealkylated at both alkyl chains in small rates (about 1 nmol x mg protein-1 x 60 min-1) by microsomes from rat liver and pig urinary bladder epithelium. NDBA and 4-OH-NDBA were dealkylated at similarly low rates by pig urinary bladder microsomes, in strong contrast to the high debutylation rates observed for rat liver microsomes. Correspondingly, SSB induction by NDBA and 4-OH-NDBA was observed in Namalva cells with NDBA and 4-OH NDBA in the presence of PB-induced rat liver microsomes but not with urinary bladder microsomes or without external activation. BCPN did not induce DNA-damage in Namalva cells (with or without external activation) or in rat hepatocytes. Significant induction of sister chromatid exchanges (SCEs) and micronuclei, however, was observed in Namalva cells after incubation with NDBA and BCPN. Our data suggest activation of BCPN via alpha-oxidation in the urinary bladder, even though activation rate in-vitro is so low that a positive response is not detectable by several short-term tests. PMID- 2588267 TI - Cadmium-induced alterations of chlorpropham metabolism in isolated rat hepatocytes. AB - In order to investigate the various steps of chlorpropham (CIPC) metabolism which could be influenced by cadmium, isolated rat hepatocytes were incubated in the presence of CIPC (0.1 mM) and of increasing Cd concentrations (0-180 microM). The results showed that Cd accumulation in hepatocytes was in good correlation to its concentration in the incubation medium. At 90 microM Cd, hydroxylation of CIPC was only slightly decreased by 30%, while CIPC hydrolysis into 3-chloraniline was unaffected by the presence of Cd. Accordingly, unchanged CIPC increased in hepatocytes. At 27 microM Cd, free 4-hydroxychlorpropham (4-OHCIPC) increased in the intracellular medium as a consequence of a strong suppression of both sulfation and glucuronidation which was related to the strong depletion of the intracellular ATP level under the combined influences of both cadmium and free 4 OHCIPC. Acetylation of 3-chloroaniline, which represents a minor pathway of CIPC metabolism, was already markedly suppressed (43%) with the lowest Cd concentration (27 microM). These in vitro results suggest that Phase II reactions are more sensitive to Cd than Phase I processes and that Cd enhanced the CIPC cytotoxicity as shown by alterations of the membrane integrity. PMID- 2588269 TI - [The effect of various concentrations of hydrochloric acid solutions on the enamel permeability for 45Ca in experimental fluorosis]. AB - In 96 months-old dogs with light fluorosis the effect of 10% HCl solution and the mixture of 36% HCl solution with concentrated HCl (1:2) on 45Ca incorporation into the superficial and deep enamel layers, and its penetration into the dental hard tissues. The increase in HCl concentration was directly related to enamel 45Ca incorporation and the depth of its penetration in fluorosis-afflicted teeth. Under effect of 12% HCl solution 45Ca penetrated across the whole enamel reaching the dentin. Further increases in HCl concentration is nonexpedient in bleaching the fluorosis-afflicted enamel. PMID- 2588268 TI - [The nature and characteristics of valence fluctuations of the functional groups in the organic structure of normal dentin and in pathology]. AB - Biopsied coronal dentin was studied in 50 permanent teeth in healthy individuals and patients with caries and pulpitis. Valent undulations of functional groups of protein matrix of dentin were studied. The characteristic absorption bands reflecting the chemical links stabilizing the protein molecular structure were determined. The course of chemical links changes was followed in caries and pulpitis which suggested the increased pathological changes in the organic matrix of coronal dentin. PMID- 2588270 TI - [Characteristics of the morphologic changes in an experimental suppurative wound of the perimandibular soft tissues treated by some types of laser radiation]. AB - In rabbits isolated CO2 and He-Ne laser irradiation promotes early granulation of wounds and accelerates epithelialization with more complete restitution of the regenerated skin organ specificity. The best effect was achieved when combined laser irradiation was applied. This was further corroborated by the immunohistochemical investigation. PMID- 2588271 TI - [Photoplethysmographic indices of hemodynamics in periodontal diseases]. AB - In 120 patients the periodontal photoplethysmography was performed. Statistical analysis of the frequency-amplitude characteristics of the photoplethysmographic signal was useful for differential diagnosis of various forms and stages in periodontal diseases and for evaluation of the treatment efficiency. PMID- 2588272 TI - [A method for the early diagnosis of caries]. AB - A method is offered to detect early enamel demineralization prior to formation of caries area which can be stained with methylene blue. The technique is based upon the detection, under the caries-eliciting superficial layer as determined after J. L. Hardwick and E. B. Manly (1952), the demineralized enamel requiring hygienic control or remineralization therapy. PMID- 2588273 TI - [Assessment of autonomic nervous system function in patients with generalized periodontitis]. AB - The 56 patients with different stages of generalized periodontitis were investigated using a simplified A. M. Vein (1971) routine. The clear preponderance of sympathetic autonomic responses over the parasympathetic ones was evident. Besides, a compensatory activation of parasympathetic nervous system was reflected in inversion responses to clinostatic and Ashner tests. PMID- 2588274 TI - [The state of the oral cavity in persons infected with the human immunodeficiency virus]. AB - The authors observed high incidence (100% among citizens of the USSR) and intensity of caries in 47 patients with diagnosed acquired HIV infection in the stage of symptom-free course and AIDS. In 2 persons out of 9 in symptom-free course of HIV infection an increase of mental lymph nodes has been observed. Significant changes of the mouth cavity mucosa were diagnosed in 67.1% of the patients. Gingivitis was observed three times as often than in the control group. PMID- 2588276 TI - [Thresholds of the electrical excitability of the pulp in various groups of teeth and their changes under the influence of analgin, amidopyrine and diazepam]. AB - Pulp electric excitability thresholds in different teeth groups and their changes under effects of analgin, amidopyrin and diasepam were studied using electro odontometry in 58 patients and in experimental recordings of neuronal activity in rostral part of trigeminal complex under electrostimulation of molar and fang teeth. Baseline thresholds of pulp stimulation proved different in anterior teeth group and premolar/molar group. Analgetic drugs used had more pronounced effect in cases of molar pulp stimulation. PMID- 2588275 TI - [The use of a supersonic-frequency current in treating inflammatory periodontal diseases]. AB - The impact of supersonic-frequency current (SFC) on the periodontium was investigated in 76 patients with chronic catarrhal gingivitis and light to mild periodontitis. SFC was shown to promote the disappearance or reduction of the size of inflammatory focus due to normalization or improvement in periodontal microcirculation. Clinical improvement was noted in 86% of the patients with chronic catarrhal gingivitis and in 88% of light periodontitis and 96% of mild periodontitis patients. PMID- 2588277 TI - [Measures for improving the prevention of stomatologic diseases in children]. PMID- 2588279 TI - [The use of the Uzor laser apparatus for treating inflammatory diseases of the maxillofacial area]. AB - This is a report on the first results of application of "Uzor" laser device in dentistry. Semiconductor lasers are used in it. Bioeffective regimens of magneto laser therapy were established to treat maxillofacial pathology. A series of techniques is offered to treat some particular diseases: arthritis, alveolitis, sialoadenitis, pericoronitis, jaw fractures. PMID- 2588278 TI - [A comparison of clinical, x-ray and surgical data in posttraumatic deformities of the naso-orbital complex]. AB - Observation and palpation could not fully determine the damage caused by trauma in posttraumatic patients. With intra-operation findings and X-ray imaging compared, the latter failed to reveal the full amount of bone destruction, except for the fractures of several parts of orbital interior walls at the level of lamina papyracea. The X-ray investigation routine comprising lateral observational view and medial zonography performed using an OP-6 device proved most effective. In cases when special devices are not available the semiaxial projection and eccentric orbital picture are most informative. PMID- 2588280 TI - [Neutrophil-macrophage correlations during the healing of suppurative wounds in patients with phlegmons of the maxillofacial area undergoing combined treatment with the use of low-frequency ultrasound]. AB - The results of investigation into neutrophilic-macrophagal relationship in purulent wound cicatrization in patients with maxillofacial phlegmons are presented. The one-factor analysis of variance was used to calculate the determination coefficient which proved that the neutrophils exert a strong influence on the mononuclear phagocytes. PMID- 2588281 TI - [Myelochondroplasty of bone cavities and defects of the jaw bones]. AB - A new transplant is designed which consists of an autologous vital bone marrow and dispersed lyophylized allogenic rib cartilage. With postsurgical cavities filled with this transplant, the regeneration of osteal tissue was clearly accelerated in the defect site. This reduced both the rehabilitation terms and complication incidence and improved the cosmetic effect in patients with extensive residual osteal cavities formed during pathological tissues extirpation. PMID- 2588282 TI - [The dynamics of the blood supply to the maxillary complex following a maxillary osteotomy]. AB - Regional maxilla hemodynamic changes were studied in 40 patients. After surgical correction of combined upper jaw deformations, the osteotomized fragment showed sufficient blood flow which originated from distal maxilla blood vessels. By 45 days after surgery the blood flow reached its preoperative level. More pronounced changes were detected in the regional blood flow in patients with combined jaw deformations after congenital labial, soft and hard palate clefts. In these patients, retardation of the blood flow restitution could reflect the scarification of the tissues of soft and hard palate, and lips. PMID- 2588283 TI - [Difficulties in the differential diagnosis of chronic interstitial parotitis and an acinar-cell tumor]. AB - Clinical pictures of parotid tumors and chronic interstitial parotitis are similar to several extent. Cytologic investigation of punctate from the suspected tumor can have a crucial value for diagnosis. Additional thorough investigation in a special clinic using any available technique is expedient in cases of cytological detection of a rarely occurring tumor. PMID- 2588284 TI - [A device for osteosynthesis in fractures of the mandibular condyle]. AB - Using the above device and fixation of osteal fragments by brackets with the storage it is possible to overcome all the differences which are observed during osteosynthesis on the condyle process of the lower jaw. The device is simple to use and, therefore, may be recommended for wide clinical use. PMID- 2588285 TI - [A modification of the masticatory test]. AB - Theoretical grounds were provided for a novel mastication test. In a group of 13 males and 12 females aged 17 to 25 with intact dentition and orthognathic occlusion the mastication was functionally assessed. Mastication effect was enhanced with increasing quantity of mastication movements, decreasing mastication capacity and efficiency. With forced mastication the effect increased, mastication capacity remained unchanged, the efficiency fell. As the test portion increased, the mastication effect, capacity and efficiency all increased. This is the first demonstration of linear correlation between mastication effect and the integral of bioelectric activity of major mastication muscles while mastication movements constant. PMID- 2588287 TI - [Allergy to gold--a cause of denture intolerance]. AB - Two cases of allergic responses to "dentistry gold" are reported. The condition was confirmed in epicutaneous tests with 2 different gold--containing substances. Removal of the dentures was the cure for these patients. Dentures fabricated using other materials (silver-palladium alloy, plastics) did not cause adverse effects in these patients. PMID- 2588286 TI - [Experimental validation of the use of the masseter muscle in treating paralysis of the mimetic muscles]. AB - In 15 rabbits the distal end of masseter muscle was surgically transposed to perioral region. After 90, 120 and 180 days the altered muscle position and reduction of functional load did not cause its degeneration. Rather, these conditions elicited a functional reordering evidenced by reduction of muscular fibers' cross-sectional area, the number of surrounding capillaries, decrease in the succinate dehydrogenase activity and increase in connective tissue layer. PMID- 2588288 TI - [The experience of using a method of radionuclide skeletal visualization in the diagnosis of temporomandibular joint diseases]. AB - The technique was applied in 12 patients with temporomandibular joint dysfunction without X-ray features of arthrosis, and in 7 patients with facial pains of unclear etiology. Radionuclide investigation data compared with clinical and X ray data, the new technique proved highly sensitive to detect early stages of temporomandibular joint arthrosis and to determine temporomandibular joint involvement in cases of facial pains. This suggests the use of the technique for screening in prosopalgia. PMID- 2588289 TI - [Local immunity in dental caries in children]. AB - Immune state was evaluated in 69 schoolchildren. In cases with dental caries, local immunity changes were evident with changes in immune globulins content. This is the first report on the presence of antigen to caries-afflicted dentin in the mixed saliva as detected by the complement binding technique. The course features of the disease were related to the salivary antibodies titer. PMID- 2588290 TI - [Evaluation of the status of the palatopharyngeal area in children with congenital penetrating cleft palate]. AB - Gypsum models were constructed to study the transversal pharynx width and palate defect in 57 children with congenital opened palate clefts. Age-dependent increase in the defect width was noted and attributed to muscular dystrophy in the soft palate and lateral walls of the pharynx as a result of their dysfunction and hypodynamia. PMID- 2588291 TI - [Deformities of the dental arch and alveolar process in children related to the removal of the lower temporary molars]. AB - A total of 279 children aged 3 to 12 years were investigated. In 59 dentition defects were detected. These were located largely (39 patients) on a lower jaw. Dentoalveolar extension was found in 28 patients aged 5 to 8 years. Dentoalveolar extension was characterized as was the position and state of dental rudiments. Of 59 children put on a regular check-up list, in 28 preventive dentures were installed to avoid secondary deformation and dentomaxillary anomalies formation. PMID- 2588292 TI - [The needs of a ship's crew for orthodontic care]. PMID- 2588293 TI - Hydroboration of 5 alpha-ergost-8-en-3 beta-ol. AB - Hydration via hydroboration of 5 alpha-ergost-8-en-3 beta-ol affords 5 alpha ergostane-3 beta, 15 alpha-diol, 5 alpha, 14 beta-ergostane-3 beta, 15 beta-diol, and 5 alpha-ergostane-3 beta, 7 beta-diol, and not 5 alpha, 9 beta-ergostane-3 beta, 7 beta-diol, as previously reported by others. PMID- 2588294 TI - Syntheses of 24R,25-dihydroxy-[6,19,19-3H]vitamin D3 and 24R,25-dihydroxy [6,19,19-2H]vitamin D3. AB - 24R,25-Dihydroxy-[6,19,19-3H]vitamin D3 with a specific activity of 54 Ci/mmol and 24R,25-dihydroxy-[6,19,19-2H]vitamin D3 with 2.6 deuterium atoms/mol were synthesized in four steps starting from 24R,25-Dihydroxyvitamin D3 via its sulfur dioxide adduct. PMID- 2588295 TI - In vitro characterization of secretion rates from silastic micropellets containing estradiol. AB - For local, controlled steroid hormone administration into tissues, such as the brain, we have prepared cylindric micropellets of 1 mm in length and 1 mm diameter. The micropellets are a mixture of silicone glue (silastic) and 0.1%, 1.0%, or 10% estradiol (E2). To evaluate in vivo E2 secretion rates, micropellets were implanted into the brains of 40 rats for either 1, 4, 8, or 12 weeks. In vitro 24 h E2 secretion rates of these implants were compared-after removal from the rat brain-with 24 h secretion rates of micropellets that had been incubated for the same periods of time in vitro only. In vitro release of E2 decreased steadily but asymptotically from the first day of incubation to the 3rd or 4th week, when an apparent steady state is achieved. With any E2 concentration the coefficient of variation for 24 h release rates rarely exceeded 15% within a group. The release rates increased nonlinearly with the concentration of E2 in the pellet. Subsequent to in vivo implantation the in vitro secretion of E2 was slightly higher than the in vitro secretion of micropellets incubated for the same period of time in vitro. Thus (1) the secretion rate from a pellet can be predicted rather exactly by the mixing ratio of silastic and E2 and (2) the secretion rate from the micropellet in vitro and in vivo appears to be rather similar. It is concluded that the method described is very useful for short-term (days) or long-term (weeks, albeit not constant) local exposure of defined tissues to steroid hormones. PMID- 2588296 TI - 18-Substituted steroids. Part 15. 6 beta-Hydroxylation of aldosterone by liver. AB - 6 beta-Hydroxyaldosterone and 6 beta-hydroxy-17-isoaldosterone, characterized by high-field NMR studies, are among the major polar metabolites formed from aldosterone by incubation with rat liver slices or microsomal fraction. It is uncertain at present whether the 17-iso product results from an enzymatic or a chemical inversion of configuration. Periodate degradation of the 6 beta hydroxyaldosterone gave 6 beta-hydroxyaldosterone gamma-lactone, identical with a synthetic sample. PMID- 2588297 TI - Overnight dexamethasone suppression test: normal responses and the diagnosis of Cushing's syndrome. AB - Serum cortisol levels were measured the morning after the administration of 1 mg of dexamethasone. Only 5 of 190 subjects had serum cortisol levels greater than 2 micrograms/dL. Thus, the normal value after dexamethasone suppression is less than 2 micrograms/dL rather than less than 5 micrograms/dL as has generally been accepted. The distinction is important because some individuals with Cushing's syndrome partially suppress their cortisol levels to less than 5 but more than 2 micrograms/dL during the test procedure. Thus, the use of 5 micrograms/dL as the normal value may lead to an unnecessary delay in diagnosis. PMID- 2588298 TI - A new method for measurements of plasma protein steroid-binding kinetics in human plasma at 37 C. AB - The equilibrium kinetics in vivo of free and protein-bound steroid hormone were examined at 37 C. Human plasma was pumped through a 1 m PVC catheter and tritiated steroid hormone continuously added at the inlet. The plasma was collected and rerun through a new catheter 24 h later. A significantly (P less than 0.05) higher uptake of steroid hormone was observed in the first parts of the catheter during the first passage when compared to the second passage. The results indicate that non-equilibrium conditions existed for testosterone (greater than 10 sec), estradiol (4 sec), estrone (greater than 2 sec), and estriol (greater than 2 sec) while no delay was observed for progesterone. The results indicate that the counter-current transfer between the testicular and ovarian vessels, respectively, may create a physiologically important, temporarily increased concentration of available hormones in the arterial blood supply to the organs. PMID- 2588299 TI - Covalent immobilization of the estrogen receptor to an electrostatically neutral N-hydroxysuccinimide ester derivative of agarose. AB - Immobilization of the estrogen receptor to the N-hydroxysuccinimide ester of succinylethylenediaminocarboxymethyl agarose (Reagent B) is described and compared with that to the charged N-hydroxysuccinimide ester derivative (Reagent A), previously described. The time course for immobilization was examined. Thirty six percent of the input receptor was immobilized within 1 h. The optimum pH in immobilization is 7.0-7.4. The dissociation rate of [3H]estradiol(3,17 beta 1,3,5(10)-estratriene) from the [3H]estradiol-receptor complex immobilized to Reagent B was similar to that in Reagent A. The receptor immobilized to Reagent B was saturated with estradiol at 5 h. The [3H]estradiol concentration necessary for saturation was 10 nM. The dissociation constant (KD) for the receptor immobilized to Reagent B was 0.95 X 10(-9) M. PMID- 2588300 TI - Relative mitogenic activities of various estrogens and antiestrogens. AB - The abilities of a variety of estrogens and antiestrogens to stimulate DNA synthesis in the prepuberal rat uterus were compared. One microgram of each compound was administered in vivo via a single intraperitoneal injection. DNA synthesis was assayed in vitro in isolated nuclei 24 h later. The relative mitogenicities of the steroidal estrogens were: 16 alpha-E2 less than 17 alpha-E2 = E3 = 16-EpiE3 less than 16 beta-E2 = 17 beta-E2. The potencies of several nonsteroidal estrogens were also tested. Indenestrol A was as potent at 17 beta E2, whereas indanestrol and dimethylstilbestrol had weaker activities. The antiestrogens, nafoxidine and 4-hydroxytamoxifen, were both potent stimulators of DNA synthesis. The abilities of an estrogen to stimulate increases in uterine wet weight, DNA polymerase alpha activities, and DNA synthesis in uterine nuclei 24 h after injection were closely correlated. Because the magnitude of the stimulation of DNA synthesis was greatest, its measurement is the most sensitive of these assays of uterotrophic activity. PMID- 2588301 TI - Long-chain fatty acid esters of 5-androstene-3 beta, 17 beta-diol: composition and turnover in human mammary cancer cells in culture. AB - Long-chain fatty acid esters of the adrenal-derived estrogen 5-androstene-3 beta, 17 beta-diol (ADIOL) were found to accumulate in four human mammary cancer cell lines (MCF-7, ZR-75-1, MDA-MB-231 and MDA-MB-330) when explosed to 10-30 nM ADIOL for variable time periods. At each time point examined, the monoester fraction, which represented the major component of the total lipoidal fraction, contained fatty acids linked to either the 3 beta- or 17 beta-positions. However, there was considerable variation in the ratio of 3 beta- to 17 beta-monoesters in the four cell lines. By means of reverse phase HPLC and referral to authentic synthesized compounds, each monoester fraction was found to contain a number of long-chain fatty acid components whose composition resembled that previously determined for the fatty acid esters formed from 17 beta-estradiol. A specific and measurable turnover of a subfraction of ADIOL-17 beta-monoesters composed of essential fatty acids (22:6, 20:4, 18:3) occurred in MCF-7 cells, and to a lesser extent in ZR-75 1 cells. No changes were observed with time in any of the components of the 3 beta- or 17 beta-monoester fractions in MDA-MB-231 and MDA-MB-330 cells. These results, coupled with other studies, now suggest that a very rapid turnover of some components of these lipoidal derivatives may be occurring. If so, it is possible that the system of acylation-deacylation may be involved in a transport mechanism for estrogens and perhaps other steroid hormones. PMID- 2588302 TI - Non-polar extracts of serum from males contain covert radioimmunoassayable testosterone. AB - Non-polar extracts of sera from human males contain immunoreactive testosterone in a form that is released by mild alkaline hydrolysis. The non-polar derivative shows no immunoreactivity with testosterone antibody prior to hydrolysis. Hydrolyzed non-polar serum extracts from ten adult male volunteers contained 2.0 +/- 0.8 (SD) ng/mL of testosterone. Neither non-polar serum extracts of normal females nor a water blank substituted for non-polar extract of serum yields any immunoreactive testosterone after alkaline hydrolysis. Testosterone palmitate hydrolyzed alone or after addition to non-polar extract of serum yields the expected quantities of radioimmunoassayable testosterone. Previously described conjugates of testosterone are polar and are neither extractable by petroleum ether nor hydrolyzable by alkali. These observations suggest that fatty acid esters of testosterone may be present in serum of human males. PMID- 2588303 TI - Synthesis of 9 alpha-hydroxysteroids by a Rhodococcus sp. AB - 9 alpha-Hydroxylation of delta 5-3 beta-hydroxysteroids (of androstane, pregnane, 24-nor- and 21,24-bisnorcholane groups) was carried out by a Rhodococcus sp., isolated from a petroleum-containing soil sample. A large number of the investigated steroids was transformed into 9 alpha-hydroxy-delta 4-3-ketones in satisfactory yields (50-90%) at high initial concentrations of the substrates (0.5-5.0 g/L). The influence of some structural features of the steroid molecule on the progress and effectiveness of the microbial transformation was also shown. PMID- 2588304 TI - 3 beta-hydroxyandrost-4-en-6-one derivatives as aromatase inhibitors. AB - The 3-formate (II), 3-acetate (III), 3-bromoacetate (IV), 3-propionate (V), 3 methyl ether (VI), and 3-deoxy-derivative (VII) of 3 beta-hydroxyandrost-4-ene 6,17-dione (I) were synthesized and tested in human placental microsomes for their ability to inhibit aromatase. II, III, and VII of this series were potent inhibitors of aromatase with the IC50's (1.7 and 3.3 microM) of the latter two comparable to that (1.2 microM) of 4-hydroxyandrostenedione. Kinetic studies showed that the three steroids are competitive inhibitors of the enzyme with Ki's of 16.0, 5.5, and 0.61 microM for II, III, and VII. Furthermore, II showed a time dependent, pseudo-first order rate of inactivation of aromatase with Ki of 20.5 microM and kinact of 1.54 x 10(-2) min-1, while III gave a time-dependent, biphasic loss of the enzyme activity. NADPH and oxygen were required for the time dependent inactivation and the substrate, androstenedione, prevented it. PMID- 2588305 TI - A convenient preparation of the side-chain lactone ring of a withanolide precursor. AB - Condensation of C22 and C21 steroidal aldehydes with ethyl 4,6-dimethyl-2-oxo-2H pyran-5-carboxylate 1 in alkaline medium, followed by decarboxylation, provides a simple route to the alpha, beta-unsaturated side-chain delta-lactone synthesis for a classical withanolide precursor. PMID- 2588306 TI - The chemistry of 9 alpha-hydroxy steroids. 2. Epimerization and functionalization of 17 alpha-ethynylated 9 alpha-hydroxy steroids. AB - Practical routes to 9 alpha-hydroxypregnenes were developed by epimerization and hydration of 17 alpha-ethynyl-9 alpha,17 beta-dihydroxyandrost-4-en-3-one. In the three different methods of epimerization which were used, the C-9 alpha hydroxy group was not susceptible to rearrangement or other side reactions. C-21 functionalized 9 alpha-hydroxypregnenes were obtained by introducing a 17 alpha halogenated ethynyl group into 9 alpha-hydroxyandrost-4-ene-3,17-dione. Epimerization and hydration by the 17 beta-nitrooxy method produced 21 halogenated 9 alpha-hydroxypregnenes, which were further converted into 21 acetoxy-9 alpha-hydroxypregn-4-ene-3,20-dione. PMID- 2588308 TI - Glutathione conjugation of synthetic steroids in isolated rat hepatocytes. AB - When designing steroid drugs with multiple double bonds, the influence of glutathione conjugation on the pharmacodynamics of drug action should be considered. We have examined the effect of canrenone, a mineralocorticoid receptor antagonist, on isolated rat hepatocytes and found that 1 mM canrenone injured the hepatocytes during shortterm incubation at 37 C, while an analogue of canrenone which bears 4 double bonds (delta 1,11-CAN) did not manifest such toxicity. To further pursue this, we prepared testosterone analogues comprising multiple double bonds as model compounds, and incubated them with freshly isolated rat hepatocytes. The viability of the hepatocytes was not influenced by any of the steroids, but some of them having a double bond at the C6-C7 position reduced the cellular glutathione levels. This was found to be due to conjugation of glutathione to the C7 position of the steroid molecule, and the rate of conjugation was accelerated when an additional double bond was introduced at C1 C2 or C11-C12 positions. The finding is interesting as glucuronidation or sulfation are common as conjugation processes of steroids. PMID- 2588307 TI - Synthesis and 13C-NMR analysis of 5 alpha- and 5 beta-cholestane-3,6-dione. AB - Starting from cholesterol a simple and efficient synthesis of 5 alpha-cholestane 3,6-dione and 5 beta-cholestane-3,6-dione is described. The 13C shielding data of C-7, C-9, and C-19 in both isomers can be used in the determination of the stereochemistry at C-5 of these compounds. The combination of 13C NMR spectroscopy and the simple synthesis of both isomers offers good opportunities for the determination of the stereochemistry at C-5 of 3,6-dioxosteroids. PMID- 2588309 TI - Needlestick injury in the OR: facts and prevention. AB - Recapping is the most common cause of preventable needlestick injury. Needlestick injury can be prevented by proper handling techniques. Needlestick injury can transmit the hepatitis virus to the victim. Double-gloving protects against fluid contamination but does not add any more protection against needlesticks than does a single glove. PMID- 2588310 TI - Participative management: the power of positive manipulation. AB - Managers may use manipulative techniques to facilitate personnel management and enhance productivity. Positive manipulation by a manager is purposeful behavior directed at positively meeting the needs of those involved in the interaction. Before a manipulative approach is used, an assessment should be made of personality characteristics and possible areas of vulnerability. Use of positive manipulation includes consideration of the needs of all involved, attention to personality characteristics, and careful selection of approaches. PMID- 2588311 TI - Overcoming the diagnosis of osteosarcoma. PMID- 2588312 TI - Is a drug-free workplace possible? PMID- 2588313 TI - Drug testing in the workplace. AB - It is estimated that on any one day, 8.9 million to 16 million employees will be working under the influence of drugs, and thus performing at only 67% of capacity. There are three possible phases of a drug testing program: pre employment drug screening; testing for probable cause following unexplained behavior or events; and random sample testing to detect use of controlled substances by employees on the job. With the high cost and potential for error involved, it is imperative to have a strategy or set of guidelines for instituting a drug testing program so that it protects the employee's rights and company's liability concerns. Employers need to make confidential Employee Assistance Programs available to all employees. PMID- 2588314 TI - On closing the circle of quality assurance. PMID- 2588315 TI - Functional properties of a new crosslinked hemoglobin designed for use as a red cell substitute. AB - A new crosslinking agent, bis-pyridoxal tetraphosphate, (bis-PL)P4, was used to prevent dissociation of the hemoglobin (Hb) tetramer. Yields in excess of 75 percent of intramolecularly crosslinked (bis-PL)P4Hb have been obtained using stoichiometric amounts of the crosslinking reagent. Some functional properties of (bis-PL)P4Hb have been evaluated in vitro and in vivo. Oxygen affinity was substantially reduced (p50 = 31 torr at 37 degrees C, pH 7.4, pCO2 = 40 torr), while the Bohr coefficient was -0.27 of H+ per mol of O2. Owing to its right shifted dissociation curve, (bis-PL)P4Hb still yielded a p50 of 15 torr at a low temperature (16 degrees C), as compared with only 3 torr for normal adult Hb (HbA). Clearance of (bis-PL)P4Hb from plasma was significantly delayed (t1/2 = 171 min, at a dose of 0.2 g/kg of body weight compared with that of HbA (t1/2 = 54 min). Heart rate, mean arterial blood pressure, and respiration remained stable or returned to normal values within hours after bolus injection of the hemoglobin. The (bis-PL)P4Hb was not excreted in the urine, in contrast to HbA (21% of the total dose of HbA appeared in the urine within the first 2 hrs). These results show that the covalent beta-beta crosslink prevents the renal excretion of (bis-PL)P4Hb, thereby significantly prolonging vascular retention. These properties, together with an increased ability to unload O2, make (bis PL)P4Hb a promising new candidate as a red cell substitute. PMID- 2588316 TI - Recruiting blood donors into a local bone marrow donor registry. AB - To date, most persons joining bone marrow donor registries have been recruited from platelet-pheresis panels. The potential of recruiting regular blood donors into bone marrow donor registry (BMDR) was explored. It was found that, with minimal effort, 6.2 percent of the age-eligible blood donors were recruited. A distinguishing feature of those who joined the BMDR was a history of frequent blood donations. Although local media attention had a major impact on recruitment, even those joining as a result of the publicity usually were regular blood donors. This program has the potential to recruit nearly 8000 volunteers from 120,000 regular blood donors over an 18-month period. PMID- 2588317 TI - Evaluation of platelets prepared by apheresis and stored for 5 days. In vitro and in vivo studies. AB - To evaluate the effect of storage on apheresis platelets collected with a closed system blood cell separator, an in vitro investigation was performed, with measurements of pH, lactate, ATP, the ratio of ATP to the total adenine nucleotide content, and adenylate kinase. Unmodified apheresis platelets and apheresis platelets with plasma added were compared with conventional platelets stored in PL-1240 or PL-732 plastic containers. During 6 days of storage, there were similar changes in all variables with one exception: the extracellular activity of adenylate kinase was lower in apheresis platelets with plasma than in the other three groups (p less than 0.01). In vivo studies were carried out with 111Indium-labeled autologous platelets in eight volunteers. Apheresis platelets with 100 mL of plasma added were stored in two 1000-mL containers (PL-732) at 22 degrees C during agitation. Platelets from one of the containers were labeled with 111Indium and transfused into the volunteer within 24 hours. Platelets from the other container were labeled after 5 days of storage and transfused into the same donor. There were no significant differences between apheresis platelets stored for 1 day and those stored for 5 days: the mean percentage of recovery was 58.4 and 57.6 percent, t1/2 was 69 and 67 hours, and the survival time was 5.5 and 5.6 days, respectively. PMID- 2588318 TI - The relative roles of major and minor histocompatibility antigens in the induction of immunologic unresponsiveness by blood transfusion. AB - Renal allograft survival may be prolonged indefinitely in some strains of rats following preoperative transfusion with whole blood from the organ donor. Similarly donor-specific transfusion results in a reduction in the proliferative response of lymph node (LN) white cells (WBCs) to donor-specific stimulators in mixed-lymphocyte culture (MLC). To determine the relative roles of major and minor histocompatibility antigens in the depression of the proliferative response, in vitro lymphocyte proliferation assays were performed using congenic rat strains as blood donors. Unidirectional MLCs were set up between haplotype disparate responder and stimulator LN cells, in cases in which the responding cells had been harvested from rats transfused with blood that shared either some, all, or none of the major histocompatibility complex genes with the stimulator strain. The proliferative response of LN cells harvested from rats transfused with blood sharing major (class I or II) or minor antigens, or both, with the in vitro stimulator cells was significantly less than the response of cells harvested from nontransfused controls. No single-locus product was more or less effective than whole blood in depressing cell proliferation. These data suggest that the beneficial effect of preoperative random blood transfusions observed in clinical transplantation may arise from the fortuitous sharing by the blood donor and the subsequent organ donor of not only a single major histocompatibility antigen but also of minor histocompatibility antigens. PMID- 2588319 TI - Red blood cell mass in autologous and homologous blood units. Implications for risk/benefit assessment of autologous blood crossover and directed blood transfusion. AB - A prospective analysis of 300 consecutively collected homologous blood (HB) units from a regional blood center and an analysis of 188 consecutively collected autologous blood (AB) units from a community hospital was conducted. Analysis of the red blood cell (RBC) mass content of these blood units revealed that HB contained 13 percent more RBC than AB: 200 +/- 1.1 vs 177.1 +/- 1.1 mL, (m +/- SE), respectively (p less than 0.05). Of 174 AB units eligible for crossover by AABB criteria for RBC mass (greater than or equal to 154 mL), 35 (20%) were below the 95 percent confidence interval range for RBC mass of HB units collected; mean RBC mass of 300 HB units was 12 percent greater than that of 174 AB units (200.1 +/- 1.1 vs 178.9 +/- 0.9 mL, p less than 0.001) and 20 percent greater than that of the 35 AB units outside the 95 percent confidence interval (200.1 +/- 1.1 vs 161.2 +/- 0.5 mL, p less than 0.001). These findings indicate that an evaluation of the issues of AB crossover for HB transfusion should include a risk/benefit analysis of AB units with lower RBC mass. These findings also indicate that the proposed changes in AABB standards regarding directed donation (DD) should consider the reduced benefits of DD units with lower RBC mass in a risk/benefit analysis of this practice, and support retention of homologous donor standards for directed donors. PMID- 2588320 TI - Exposure to hepatitis via directed blood donations. PMID- 2588321 TI - Unacceptable platelet counts and pH in PVC blood bags. PMID- 2588322 TI - Controversies in transfusion medicine: should donor hemoglobin standards be lowered? PMID- 2588323 TI - Infectious disease markers in autologous blood. PMID- 2588324 TI - Blood bank of the future. PMID- 2588325 TI - Production of transgenic mice: acupuncture needle-facilitated embryo transfer to oviduct ampulla. PMID- 2588326 TI - This and that: exotic foods--prophylaxis and peril. PMID- 2588327 TI - Adenosine and morphine. PMID- 2588328 TI - [The effect of the laser microirradiation of the cell center on neutrophil motility]. AB - The cell center of human neutrophils spread on polylysine-coated coverslips was irradiated with an argon laser microbeam. After the cells were pretreated with acridine orange, the irradiation of the cell center in a dose of over 0.1 J completely and irreversibly suppressed the motility of neutrophils (both random migration and chemotaxis), even though the cells retained their polarization. The same dose, applied to the cell nucleus and the forward and backward edges of the cytoplasm, resulted in little, if any, effect on cell motility, and did not inhibit their movement toward the target. Electron microscopy of the cells with the irradiated center showed the microtubules to persist for no less than 30 minutes; no visible destruction was caused in the cell center structure. Consequently, the cell center directly controls (not through polymerization of microtubules) the motility of neutrophils. PMID- 2588329 TI - [An evaluation of the fine structure of a human lymphocyte population based on the data of 2-color flow immunofluorimetry]. AB - A set of 2n basis lymphocyte subpopulation, distinguishing by the presence of at least one antigen, may be composed for a given combination of n surface antigens. The relative amounts of basis subpopulations constitute a thin subpopulation structure of lymphocytes. General methods of lymphocyte phenotyping using one (or two) differentiation antigen give actually the estimation of a sum of basis subpopulations expressing a given antigen (or some combination of two antigens). The mathematical method was elaborated for reconstruction of the thin subpopulation structure by fitting the relative assemblage of biparametric cytofluorograms. The proposed approach was used for the subpopulation analysis of lymphocytes from patients with different forms of immunological deficiency. PMID- 2588330 TI - [Cytoskeletal regulation of the sensitivity of brain synaptosomes to the depolarizing action of veratrine]. AB - Using a radioactive permeant cation 3H-tetraphenylphosphonium, the sensitivity of rat brain synaptosomes to depolarizing action of veratrine, which specifically opens the sodium channels, was compared before and after destruction of microtubules and microfilaments. Depolymerization of microtubules with colchicin and vinblastine decreased an apparent affinity of veratrine to its receptor in the channel, while destruction of microfilaments with cytochalasin B had the opposite effect. Colchicine did not change allosteric interactions between the receptor for veratrine and that for scorpion venom in the sodium channel evaluated by the ability of scorpion venom to facilitate veratrine-induced depolarization of synaptosomes. It is suggested that two main cytoskeleton subsystems control the state of sodium channels in the nerve ending. PMID- 2588331 TI - [General and primary thermoresistance in genetically differing variants of murine neuroblastoma]. AB - General and primary thermoresistance of mouse neuroblastoma clonal cell lines derived from N18A subline was studied: the N18A1 clonal cell line was not treated by heat, the NTR1 was obtained by one-step selection for resistance to the long action of the temperature 40 degrees C, the NHSR1 was obtained by multistep selection for resistance to short-time treatment at 44 degrees C. The NHSR1 clonal line was shown to have higher general and primary thermoresistance by comparison with that of N18A1 cells. The NTR1 cell line, capable of unlimited proliferation at 40 degrees C, did not differ in general resistance but displayed a slower primary resistance compared to that in the N18A1 cells. Cells of all the three clones were found to be capable of temporary increasing in primary thermoresistance, i.e. hardening. A possible contribution of the primary resistance into the general one in cells of all the selected clones has been discussed. PMID- 2588332 TI - [4th meeting of the Mediterranean Medical Cooperative. Tunis, 10-13 September 1989. Abstracts]. PMID- 2588333 TI - [The effect of ionic strength on reversible inhibition of catalytic activity of acetylcholinesterase by thione phosphonates]. AB - The effect of ionic strength was used to analyze the mechanism of reversible acetylcholinesterase inhibition by three alkoxymethylthionphosphonates. The most considerable realization of the hydrophobic interaction with the surroundings of the enzyme esteratic site was marked for n-butyl derivative (compound I). The replacement of piperidine by morpholine (compound II) resulted in a decrease of the anticholinesterase activity by an order due to enhancement of the inhibitor hydrophilicity. An increase of MgCl2 concentration promotes an enhancement of the uncompetitive component contribution for compound III contrast to compound II. Hydrophobicity of the phosphoryl part of the compound I molecule is balanced under hydrophobic interaction of the heterocyclic "cationic head" with the enzyme anionic site. The break of this equilibrium intensifies the allosteric regulation, on the one hand, and lowers the inhibitor efficiency, on the other hand. PMID- 2588334 TI - [The effect of pH and pO2 changes in the blood on the energy metabolism of human erythrocytes in old age]. AB - Changes in pH and pO2 of the blood have been studied for age peculiarities of their effect on the glycolysis rate and the content of ATP and 2,3 diphosphoglycerate (2,3-DPG) in erythrocytes (in vitro). The fresh venous blood of practically healthy young (aged 20-29) and old (aged 75-85) people was used. Acidosis was shown to induce inhibition of glycolysis and decrease of the ATP and 2.3-DPG concentrations in erythrocytes, while alkalosis and hypoxemia-an increase of the glycolysis rate and 2.3-DPG content. In the both cases changes in the indices studied were considerably lower in old people as compared to young ones. PMID- 2588335 TI - [Retinol-binding glycolipoproteins in secretions of the intermediate zone of the chicken glandular stomach]. AB - Glycolipoconjugates of mucin from the intermediate zone of the hen glandular stomach is shown to include at least 5 glycolipoprotein threads with equal molecular weight of about 10 kD but with different lipid content and amino acid composition. Retinol is bound only to 2-3 glycolipoproteins which contain the highest quantity of covalently bound lipids. The retinol-binding with mucin glycolipoprotein threads, probably, occurs like the lipid-lipid interaction; neutral carbohydrates do not participate in this process. PMID- 2588336 TI - [Kinetics of inhibition of aldehyde dehydrogenase isoenzymes of rat liver by fluorine-containing disulfides]. AB - New disulphides synthesized on the basis of dithiocarboxylic acid derivatives and heterocyclic thiols containing the fluorine atoms were studied as applied to inhibit aldehyde dehydrogenase (ALDH) isozymes of the rat liver mitochondria. The most effective rat liver inhibitors of ALDH isozymes were revealed. Inhibition of the rat liver isozymes by disulphides I, II, IV, VI-VIII and fluorinated pyridine disulphide was found to be irreversible. The values of isozyme inactivation rate constants are reported. The ALDH inhibition by disulphides I, IV, VI-VIII was competitive both for the cofactor and for the substrate of the reaction. The protective effect of the NAD+ against ALDH I and II inactivation by disulfiram and disulphides I, IV, VI-VIII and X is shown. NADP+ protects isozyme II against inactivation by disulfiram and also disulphides I, VI-VIII. PMID- 2588337 TI - [Thiamine diphosphate pool and its biosynthesis in the liver in galactosamine hepatitis]. AB - The hepatitis-like changes were induced in the liver of albino female rats weighing 120-150 g and fed on the appropriate vivarium diet by single parenteral administration of hydrochloride galactosamine in a dose of 0.9 or 1.8 mmol per 1 kg of body weight. The thiamine diphosphate level in the cytosol fraction of the liver decreased 24 h after the preparation administration, the same in blood but with the higher dose used. The activity of pyruvate dehydrogenase, a thiamine diphosphate dependent enzyme, decreased similarly. The cytosol transketolase activity lowered by 38-39%. The coenzyme biosynthesis disturbance due to a fall by 49-58% in the thiamine pyrophosphatase activity is considered to be responsible for hydrochloride galactosamine-induced decrease in the thiamine diphosphate pool. Specificity of the thiamine diphosphate pool disturbance and discoordination of thiamine diphosphate dependent enzymes in the liver are observed under administration of hydrochloride galactosamine. PMID- 2588338 TI - [Activity of various enzymes of energy metabolism in the rat kidney and intestines in vitamin D and K deficiency]. AB - The vitamin D and K deficiency was studied for its effect on creatine kinase, phosphorylase and alkaline phosphatase activity of rat kidneys and intestinal mucosa. The results show that creatine kinase and phosphorylase activity of kidneys varies depending on the content of these vitamins, e.g. it is activated with vitamin D depletion irrespective of the vitamin K status and remains unchanged with the deficiency of vitamin K alone. In this case the vitamin D deficiency affects kidney phosphorylase and intestinal mucosa differently. Data obtained and those available in literature permit suggesting that the deficiency of the same vitamin may exert a different action on the activity of isoforms of such enzymes as creatine kinase and phosphorylase. PMID- 2588339 TI - [The effect of functionally bound vitamins and their coenzyme forms on the activity of 2-oxoacid dehydrogenases in mouse organs]. AB - Ever-growing doses (beginning from the therapeutic up to 10-fold doses of a complex of five functionally bound vitamins (B1, FMN, nicotinamide, pantothenate, lipoic acid) being administered to F1 mice (CBA x Black) induced a constant and considerable rise of the pyruvate- and 2-oxoglutarate dehydrogenase (PDG and OGDG) activity in the mouse organs. In the in vitro experiments the addition of the corresponding coenzymes or their mixture (in the optimal concentrations) to the incubation medium containing mitochondria of the mouse liver led to a greater activation of these dehydrogenases in the group of animals which were preliminary injected the above complex of vitamins. PMID- 2588340 TI - [The effect of vitamin E deficiency on enzyme activity and the status of the membrane fraction of rat liver microsomes]. AB - The vitamin E deficiency was studied for its effect on the activity of enzymes participating in metabolism of xenobiotics. Experiments with 54 rats have demonstrated that the maintenance of animals on the vitamin-E-deficient diet within 13-14 weeks decreases the activity of microsomal monooxygenases (demethylase and hydroxylase), NADH- and NADPH-reductases, aryl- and aliesterases in the liver and lungs, which is a result of disturbance of hydrophobic and polar interactions in microsomal membranes. Vitamin E deficiency makes the extent of solubilization of these enzymes higher under the influence of deoxycholate and trypsin and intensifies inactivation of these enzymes under the effect of urea. In the lungs and in the liver of the vitamin E deficient rats the content of reduced glutathione decreases as well as the activity of glutathione reductase, glutathione-S-transferase, aldehyde dehydrogenase, while the activity of gamma glutamyltransferase increases; glutathione disulphide is accumulated. PMID- 2588341 TI - [The effect of alpha-tocopherol and ionol on the physical structure of the membranes of rat liver microsomes under conditions of antioxidant insufficiency]. AB - Physiochemical conformity of the alpha-tocopherol interaction with hepatic microsomal membranes has been studied by means of fluorescent probes (pyrene and 1-anilinonaphthalene-8-sulphonate). The microsomal membrane microviscosity is shown to sharply decrease under conditions of the antioxidant deficiency with vitamin E expelled into animals normalizes microviscosity, but feebly influences the microsomal surface charge. Microcalorimetry has been used to establish that penetration of tocopherol into microsomal membranes was accompanied by the exothermic effect. PMID- 2588342 TI - [The effect of alcohols on daily variations in aspartate amino- transferase activity in rat organs]. AB - The 7 day-long intragastric administration of ethanol and ethyleneglycol in a dose of 1/3 DL50 was studied for its effect on the circadian variations of the aspartate aminotransferase activity (AST, EC 2.6, 1.1) in the liver, brain, myocardium and kidney of male rats. The ethanol and ethylene glycol administration reduced the mean circadian enzymic activity in the above organs. Moreover, ethanol significantly reduced the amplitude of circadian variations of the AST activity in the liver, brain and kidney, while ethylene glycol--in the liver, myocardium and kidney. PMID- 2588343 TI - [Kinetic characteristics of the pyruvate transport system in the wheat chloroplast envelope]. AB - Kinetics of pyruvate transport through the envelope chloroplast vesicles has been studied. For wheat cultivar Bezostaya-1 Km is 26 mM, Vmax--33 Mmol/l h per 1 mg of protein, Hill's coefficient--0.56 and the coefficient of temperature inactivation at 40 degrees C is 0.045 min-1. 7 mM Mg or Ca ions for optimal activity of the system are needed. Chloroplast treatment with trypsin increases the pyruvate transport intensity. The simple analytical method is suggested for pyruvate determination at the concentration of 10-150 micrograms/ml. PMID- 2588345 TI - [Cellular retinol-binding proteins of the mucous membrane of the intermediate zone of the glandular stomach in chickens]. AB - The cellular retinol-binding proteins with the molecular weight of 14 and 53.5 kDa have been isolated from the intermediate zone mucosa cells of the glandular stomach in chickens. No substantial differences in the amino acid composition of the investigated proteins have been found. The possible functional role of the isolated cellular retinol-binding proteins is discussed. PMID- 2588344 TI - [The effect of oxytocin and sigetin on Ca2+ transport in the fraction of plasma membranes of myometrial cells]. AB - Oxytocin and sigetin were studied for their effect on the active and passive transport of Ca2+ in the fraction of myometrium sarcolemma in women. Oxytocin (5.10(-7) M) introduced into the sarcolemma vesicles and sigetin (5.10(-3) M) added into the incubation medium inhibit Mg2+, ATP-dependent accumulation of Ca2+ in these structures. The both agents in the mentioned concentration do not affect the passive release of cation from vesicles. A conclusion is drawn that inhibition of the calcium pump of myometrium cell plasma membranes underlies the physiological action of oxytocin and sigetin as stimulators of the contractile activity of the myometrium. PMID- 2588346 TI - [Preparation of catalytic subunits of cAMP-dependent protein kinase from cattle myocardium]. AB - A method is suggested for obtaining a catalytic subunit of cAMP-dependent protein kinase from the cattle myocardium. The specific activity of protein kinase is 0.5 mumol 32P per 1 mg of the enzyme. The method is based on the difference of protein kinase in the subunit and choloenzyme charges, it embraces the stages of homogenization, ultracentrifugation and biospecific elution on anion exchanger of DEAE-Sepharose-CL-6B using 10(-4) M cAMP in the stationary variant. PMID- 2588347 TI - [Cathepsin H activity in the human brain and human brain neoplasms]. AB - The human brain cathepsin H is shown to be a specific cysteine aminopeptidase with the optimum activity at pH 6.0. Human brain tumours of neuroectodermal (astrocytomas and glioblastomas) and epithelial (meningiomas) origin were used to study the cathepsin H activity in the malignant brain tissue. A significant increase in the aminopeptidase cathepsin H activity was found in malignant human brain tumours as compared to benign tumours and normal brain tissues. PMID- 2588348 TI - [Changes in lactate dehydrogenase activity in chicken tissues in hyperthyreosis in ontogenesis]. AB - The lactate dehydrogenase activity in reactions of lactate oxidation and synthesis was studied in subfractions of the chicken brain, heart and liver at the embryonal, early postembryonal and adult stages of development after thyroxine administration. It has been shown that during embryogenesis thyroxine predominantly enhanced the rate of lactate oxidation in the mitochondrial tissues. A marked increase in the lactate synthesis was found in cytoplasm of the adult chicken tissues. Specificity of enzyme activity alterations was detected in the chicken brain during ontogenesis after thyroxine administration. PMID- 2588349 TI - [The effect of Ca2+-phospholipid dependent phosphorylation on passive calcium transport in the myocardial sarcolemma]. AB - Protein kinase C in vesicular preparations of the myocardium sarcolemma is shown to phosphorylate proteins with the molecular weight of 250, 140, 67, 58, 24 and 11 kD. The exogenic protein kinase C catalyzed phosphorylation of the sarcolemma preparations lowers the initial rate of the passive calcium transport from 0.56 down to 0.18 mmol per 1 mg second. Activation of endogenic protein kinase C by 4 beta-phorbol-12 beta-myristate-13 alpha-acetate is also accompanied by phosphorylation of vesicular preparations of sarcolemma and by inhibition of the passive calcium transport. Polymyxin B, being an inhibitor of protein kinase C, suppresses the phosphorylation and thus prevents the inhibitory action of phosphorylation on the passive calcium transport. PMID- 2588350 TI - [Rapid simultaneous isolation of microsomes and plasma membranes from neuroblastoma C 1300 N 18 cells]. AB - The method is suggested to isolate simultaneously microsomes and plasma membranes of neuroblastoma S 1300 N 18 cells by means of differential centrifugation in the step density gradient of Percoll/Ficoll with a high degree of purification determined from the activity of marker enzymes (acetyl cholinesterase Na+,K+ ATPase, alkali phosphatase, glucose-6-phosphatase, succinate-dehydrogenase, acid phosphatase) as well as from the content of DNA and RNA and with a sufficiently high protein yield. The purified fractions of microsomes and plasma membranes are established to contain no phosphatidyl glycerol and cardiolipin--safety markers of mitochondrial membrane purification. A degree of separation of microsomes, plasma membranes and proteins dissolved in cytosol may be estimated by the activity of the cholesterol-synthesizing system of enzymes with the use of sterol transferring protein. PMID- 2588351 TI - [Interaction of melittin with model membranes: effect on the size and permeability of liposomes]. AB - The influence of melittin, a monomer devoid of the phospholipase activity, on the size and permeability of liposomes from egg lecithin (PC), dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) has been investigated by the methods of fluorescence spectroscopy, quasi-elastic light scattering and freeze-fracture electron microscopy. While studying calcein release from liposomes under the influence of melittin it has been shown that binding of melittin with a bilayer is a fast process which depends on the concentration lipid: protein (Ri) ratio as well as on the phase state of the lipid. The lipids being in the liquid-crystalline forms (PC and DMPC) are characterized by a more rapid release of the dye-stuff from liposomes than DPPC vesicles being in gel state with the same Ri. Under the influence of different melittin concentrations heterogeneity of the system and its medium hydrodynamic size of particles at first increases (100 less than or equal to Ri less than 500) due to their fusion and then these parameters decrease to the initial values. PMID- 2588352 TI - [Preparation of highly-purified melittin from bee venom by an affinity chromatography method]. AB - The method of melittin (a lytic peptide from bee venom) purification is described. The method is based on application of immunosorbent with antibodies against phospholipase A2 and permits obtaining peptide without the residual phospholipase activity. It can be also used for the phospholipase A2 purification from melittin admixtures. PMID- 2588353 TI - [Kinetic characteristics of 6-phosphogluconate dehydrogenase from bull adrenal cortex]. AB - The hyperbolic dependence of the initial rate of 6-phosphogluconate dehydrogenase catalyzed reaction on 6-phosphogluconate and NADP concentrations has been established. The Lineweaver-Burk plots of V0 against concentration of one substrate with constant unsaturating concentrations of another substrate cross left from the ordinate axis. The Km value for 6-phosphogluconate is equal ot 0.035 mM, for NADP--0.018 mM. It has been shown that NADPH inhibits 6 phosphogluconate dehydrogenase by the competitive type with respect to NADP and by the noncompetitive one with respect to 6-phosphogluconate. Ribulose-5 phosphate inhibits the reaction by the mixed type with respect to NADP and by the noncompetitive type with respect to 6-phosphogluconate. Kinetic data are in agreement with the consecutive mechanism of the reaction: the first substrate is NADP, the last product--NADPH. The Arrhenius plot for the reaction shows a break at 27 degrees C. PMID- 2588354 TI - [Alcohol dehydrogenase reaction on activated charcoal]. AB - The alcohol dehydrogenase reaction on active charcoals has been studied. It is shown that the reaction rate on active charcoals decreases in comparison with usual conditions but the reaction being carried out for a longer period of time, the equilibrium shifts towards the NADH formation, which makes the NADH yield several times higher. A conclusion is made on the possibility of charcoals to influence the enzymic reactions in a living organism. PMID- 2588355 TI - [Percutaneous pulmonary balloon valvuloplasty in Denmark]. AB - Percutaneous balloon valvuloplasty of valvular pulmonary stenosis (PPB) was carried out for the first time in 1982 and is now regarded as the primary method of treatment of this condition. The results of the first PPB treatments in Denmark are presented here. PPB was planned in 28 patients and was carried out in 25 (22 children and 3 adults). PPB was carried out on two occasions in one patient. Twenty-three patients had isolated valvular pulmonary stenosis and two patients had Fallot's anomaly. No complications of significance occurred after the treatments. The average gradient for all dilatations was 77 +/- 24 mm Hg prior to and 36 +/- 23 (p less than 0.0001) immediately after PPB. The gradient was reduced by more than 50% in 68% of the patients. In 14 patients, the gradients over the pulmonary valve was measured by Doppler technique or by cardiac catheterization greater than 6 months after PPB. In these patients, the average gradient was 69 +/- 21 mm Hg prior to PPB, 29 +/- 12 mm Hg (p less than 0.0001) immediately after PPB and 27 +/- 9 mm Hg (p less than 0.0001) at the most recent control examination, on an average 12 months (range 6-24 months) after PPB. In the same patient group, significant reduction of the electrocardiographic right-sided hypertrophy was found at the most recent control examination. It is concluded that PPB is an effective and safe treatment of valvular pulmonary stenosis. PMID- 2588356 TI - [Treatment of hydatidosis with albendazol]. AB - Eight patients with hydatidosis treated with albendazol in daily doses of 10 mg/kg daily in courses of 28 days (4-6 courses) were analysed. The patients came from Morocco, Spain, Turkey and Yugoslavia. Seven patients had a cyst (or cysts) in the liver and one had also cysts in the kidneys. One patient had cysts in the muscles of the extremities. As assessed by ultrasonic scanning, computed tomography of the cysts, general condition, serology and the presence of hydatid antigen in the serum, treatment was effective in six patients. One patient developed an allergic reaction to albendazol. All of the patients had varying degrees of liver involvement which were reversible. Neutropenia did not occur. Various parameters for assessing the therapeutic effect are mentioned. Albendazol appears to be effective in the treatment of non-operable hydatid disease and to prevent recurrence after surgery. PMID- 2588357 TI - [Isovaleric acidemia]. AB - The three first cases of isovaleric acidemia diagnosed in Scandinavia are described. The disorder is characterized by periodic vomiting, lethargy and coma accompanied by ketoacidosis and a "sweaty feet" odour. These attacks are often triggered of by upper respiratory tract infections or by ingestion of large amounts of protein. Often there are feeding difficulties because these children have aversion to protein-containing foods. Isovaleric acidemia can be subdivided into two types: an acute neonatal form and a chronic intermittent form. The basic defect is deficient activity of isovaleryl-CoA dehydrogenase, resulting in increased urinary excretion of mainly isovaleryl-glycine and 3-hydroxy-isovaleric acid. The defective gene is assigned to the long arm of chromosome 15, and at least five different mutations among 15 patients have been demonstrated. Therapy is symptomatic with correction of the metabolic acidosis and protein restriction and long term treatment with oral glycine and possibly carnitine. PMID- 2588358 TI - [The accuracy and reproducibility of clinical examination of adenoma of the thyroid--corrected for randomness with iota and kappa]. AB - The aim of this study was to evaluate the reliability (accuracy and observer variability) of the clinical examination of the thyroid gland for adenomatous changes. All patients (n = 105) admitted for scintigraphic examination of the thyroid gland were examined by three observers and the thyroid scintigraphy was performed. The study population consisted of the patients (n = 84), where the result of the scintigraphic examination could be classified as either "normal" (n = 24), "solitary adenoma" (n = 32) or "nodular goitre" (n = 28), with scintigraphy used as golden standard. The accuracy was evaluated using each observer's sensitivity, specificity and total agreement with the golden standard for each diagnosis and the observer variability by the overall agreement between each pair of observers. After random agreement was eliminated by calculation of iota and kappa, the results showed a fair reliability of the clinical diagnoses "normal" and "solitary adenoma" (iota between 0.20 and 0.62; kappa between 0.33 and 0.46), but poor reliability for "nodular goitre", (iota between 0.00 and 0.50, kappa between 0.00 og 0.46). Calculation of the newly introduced iota is discussed in the appendix. PMID- 2588359 TI - [Intermittent claudication--social aspects in young patients not undergoing surgical treatment]. AB - A total of 107 patients suffering from intermittent claudication (CI) was studied after a mean observation time of 5.9 years. Thirty-one (29%) had died during the observation period. A questionnaire was sent to 76 patients and 78% replied. All patients were under 50 years of age at the first consultation. No patients had been operated upon. The ratio women:men was 1:1.3. 33% received disability pensions or some other kind of pensions. Fifty-eight had limited their spare-time activities because of CI. It is concluded that a close control and reconstructive arteria surgery must still be recommended when the working ability is threatened. PMID- 2588360 TI - [Surgical treatment of chronic maxillary sinusitis. Report of a new surgical technic and an evaluation of results of traditional surgery]. AB - During recent years, a new operative procedure for treatment of chronic maxillary sinusitis has been strongly recommended as being more effective and more physiological than the traditional Caldwell-Luc operation. The principle of the method is endoscopically guided endonasal resection of the anterior ethmoid cells and enlargement of the natural ostium of the maxillary sinus in the middle meatus. In contrast, the principle in the Caldwell-Luc operation is opening into the sinus in the canine fossa, providing direct approach to the lumen, and finally creation of a fenester towards the inferior meatus. However, the publications hitherto presented have not documented clearly the efficiency of this new method, which also appears to have an increased risk of complications, some of which are serious. The present study elucidates the efficiency and side effects of the traditional Caldwell-Luc operation in 77 patients (107 maxillary sinuses). Four to nine years after the operation 73% of the patients had had satisfactory subjective effect of the operation. Consistency was present between the subjective estimation and the objective findings at follow-up. The effects included only slight disturbances of the sensibility in the infraorbital nerve (n = 9) or teeth (n = 6). However, only two patients (3%) had more troublesome change of the sensibility in the infraorbital nerve and in one patient only a subjectively "dead" tooth was also avital at vitality testing. The survival of the teeth was estimated roughly by comparison of the number of teeth on the operated side versus the non-operated side and was unimpaired.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588361 TI - [Extracorporeal treatment of poisoning. An analysis of 72 consecutive cases from the period 1977-1988]. AB - During a period of 12 years, extracorporeal treatment of 72 cases of poisoning in the form af dialysis and/or haemoperfusion was undertaken in Medical Department C of Arhus Municipal Hospital. Where 54 patients were concerned, the causes of poisoning were medicinal. Eleven cases were caused by ethyl alcohol, six were caused by technical poisons and one by cantharidine which is employed in veterinary medicine. In 50 cases the primary indication for extracorporeal treatment was elimination of the drug or other poison. In the remaining 22 cases the indication was acute renal failure. The total mortality was 4%. PMID- 2588362 TI - [Hidden statistics of traffic accidents]. AB - Only 19% of the 3,071 injured persons who were treated in the casualty department of Odense Hospital following traffic accidents in 1987 could be found again in the police registers of traffic accidents from the same region. All of the registrations from the police registers from the central region could be found again in the casualty department. In 1971, the corresponding coverage was 36%. The degree of coverage is particularly low for single bicycle accidents, other bicycle accidents, other single accidents and the hours immediately after midnight. Considerable disagreement exists concerning registration of the use of safety belts and crash helmets. In Odense, the municipal road authorities utilize the localization of the accidents reported by the casualty department. The decrease in the degree of coverage is due mainly to an increasing proportion of bicycle accidents. Where casualties require admission to hospital, the coverage is approximately 75%. This has remained unchanged throughout the years and it is therefore suggested that this proportion should be employed as indicator of the effect of the majority of prophylactic measures. In addition, proposals are made for simplification of the police registration forms. PMID- 2588363 TI - [Percutaneous mitral balloon valvuloplasty in a patient with mitral stenosis]. AB - Percutaneous balloon valvuloplasty of mitral stenosis was described in 1984. The subsequent results were promising and the method appears to be capable of replacing surgical valvotomy. Mitral balloon valvuloplasty in a patient with non calcified rheumatic mitral stenosis is described here. PMID- 2588364 TI - [Soft tissue tumors, particularly intramuscular lipomas]. AB - The pathology, clinical features and treatment of intramuscular lipomata are reviewed on the basis of two case reports. The intramuscular lipoma is a benign tumour which feels hard on contraction of the muscle involved in comparison to ordinary lipomata. PMID- 2588365 TI - [Reversible hearing impairment after meningococcal meningitis]. AB - A case of partial and fluctuating cochlear hearing loss persisting one year after meningococcal meningitis is presented. Repeated audiometry after the recovery from the disease is recommended in all patients. PMID- 2588366 TI - [What is the real advantage of reducing cholesterol?]. PMID- 2588367 TI - [Prescription of psychopharmaceuticals in general practice]. PMID- 2588368 TI - [A method to find alertness, brain relaxation, stress reduction, improved vision and more energy]. PMID- 2588369 TI - [Psychosocial support of families with children with cancer]. PMID- 2588370 TI - [Informations on oncologic epicrises contained in medical records]. AB - The informative content of summaries concerning 96 patients in whom the diagnosis of cancer of the breast was established in 1986 in local and regional hospitals in Denmark was investigated. The informative content of the summaries were illustrated by investigation of the extent to which the summaries contained information about the diagnosis, treatment, laboratory investigations, information to the patient and her relatives and information about contact with the general practitioner. In addition, summaries from the regional hospitals were investigated as regards information about the prognosis and the medical and sociomedical therapeutic plan. Information about the diagnosis, treatment, laboratory investigations and the medical therapeutic plans was, as a rule, provided in the summaries. Information about information to the relatives, prognosis and the sociomedical therapeutic plan for follow-up control by the general practitioner was scarcely ever provided in the summaries. Information to the patient was mentioned in less than half of the summaries from local hospitals and in less than 20% of the summaries from regional hospitals. This investigation reveals that the summaries lack valuable information. PMID- 2588371 TI - [Diagnosis of penicillin allergy. Results of a clinical investigation program]. AB - Investigations concerning penicillin allergy (PA) from abroad suggest that considerable overdiagnosing occurs. The absence of standardized commercially available preparations for skin testing and the time necessary for thorough testing are also contributory causes. Fifty patients with suspected PA were investigated with a programme consisting, in serial order, of RAST for IgE to penicillin V and G, a cutaneous test with a commercially available test preparation (Penkit), first with a prick followed by intracutaneous testing and finally with oral provocation. If a positive reaction occurred, the test was discontinued. Six patients (12%) had positive RAST or cutaneous reactions, (1 positive to RAST, 2 to prick and three not until the intracutaneous test), while no patients with negative RAST and cutaneous tests reacted to oral provocation. No generalized allergic reactions occurred during testing. It did not prove possible to predict which patients would react positively on the basis of the case histories. This investigation thus demonstrates that PA is also considerably overdiagnosed in Denmark and that a programme of investigation such as this is suitable for testing for PA and, finally, that the programme of investigation can scarcely be simplified. PMID- 2588372 TI - [Attitudes of staff at surgical departments in Denmark to surgery of suspected appendicitis. A questionnaire study]. AB - All Danish surgical departments were asked whether they would recommend removal of the appendix if this seemed normal at operation for suspected appendicitis. 14.0% recommended removal of a normal appendix only if there were no other pathological findings. 84.6% would remove the appendix under certain circumstances bearing risk factors in mind. PMID- 2588373 TI - [Cerclage surgery--a possible treatment/prevention of cervical insufficiency]. AB - The incidence of cervical incompetence is 0.1-1%. A retrospective study of a six year period in the University Hospital of Copenhagen, Hvidovre is presented. This includes 37 women, all of whom were treated surgically on 44 occasions with cerclage on account of incompetence of the cervix. The duration of the pregnancy after operation was longer in women operated in a quiet phase, without cervical effacement and with an internal os smaller than 3 cm. Women with an internal os dilated to more than 3 cm at the time of operation all terminated their pregnancies within three days. This study showed good results if the operation was carried out at a quiet phase, when the internal os was less than 3 cm and when no bulging of the membranes was apparent. PMID- 2588374 TI - [Attitudes to the use of vaginal cytologic examinations in general practice]. AB - In June 1988, a questionnaire was sent to 221 Danish general practitioners chosen at random and to 195 registrars who had applied for postgraduate courses in general medicine. The percentage replies were 83 and 73, respectively. Employing the questionnaire, information was obtained about the doctor's employment of CS on the basis of definite case reports and the doctor's assessment of the certainty of the examination. The investigation revealed that there was a general tendency to freer indications than those officially recommended, that younger women were examined more frequently than recommended, that elderly patients were examined less frequently than recommended and that considerable excessive employment of CS took place in women with condylomata and herpes genitalis. As a rule, the doctors overestimated the reduction in the risk of disease obtained by CS. It is concluded that information from the official authorities concerning employment of CS sent to general practitioners is not satisfactory and that this should be considered in extension of future guidelines about the employment of methods of examination. Precise and effectively distributed information about rationel employment of an examination must be considered to be an important way in which to obtain optimal utilization of resources. PMID- 2588375 TI - [Tracheal tube obstruction caused by local anesthetic gel]. AB - A case report of tracheal tube obstruction caused by a thin, almost invisible, membrane is presented. It was found probable that the membrane consisted of dried local anaesthetic gel. An experimental study showed that inadvertent application of 0.3 ml of lignocaine or prilocaine gel at the orifice of the tube may result in the formation of such a membrane. After 48 hours, the membrane resisted any pressure that might be generated in a resuscitation bag. PMID- 2588376 TI - [Pseudoaneurysm of the deep femoral artery after osteosynthesis of a pertrochanteric fracture of the femur]. AB - A woman aged 66 years developed a pseudoaneurysm from the deep femoral artery after osteosynthesis of a pertrochanteric fracture of the femur. During operation, it is important to avoid boring into the soft tissues on the medial aspect of the thigh and a screw of the correct length should be chosen. PMID- 2588377 TI - [Klinefelter's syndrome associated with primary mediastinal germinal cell tumor]. AB - A case of a man aged 25 year with Klinefelter's syndrome (KS) associated with a primary malignant germinal cell tumour is presented. Echocardiography was of assistance in the diagnosis as a tumour behind the heart was demonstrated. If patients with KS develop cardiopulmonary symptoms, referral for x-ray of the thorax is recommended. If there is enlargement of the heart or increase in width of the mediastinum, echocardiography should be performed. This case history emphasizes further that a negative cytological test does not disprove malignancy. PMID- 2588378 TI - [Autopsies are seldom performed in Denmark. The frequency of autopsies in Denmark 1970-1987]. PMID- 2588379 TI - [Local therapy of herpes zoster pain]. PMID- 2588380 TI - [Cimetidine and creatinine clearance]. PMID- 2588381 TI - [Creatinine clearance as a goal for the glomerular filtration rate]. PMID- 2588382 TI - [Immunosuppression in psoriasis patients]. PMID- 2588384 TI - [Narcotics and their suppression]. PMID- 2588383 TI - [Diagnosis of dementia and the painter syndrome]. PMID- 2588385 TI - [Pinacidil (Pindac). A peripheral vasodilator agent with a new mechanism of action]. PMID- 2588386 TI - [The tower of Babel of terminology concerning lymphokines and interleukins (cytokines)]. PMID- 2588387 TI - [Unnoticed loss of renal function during treatment with angiotensin I converting enzyme inhibitor. A new risk in patients with unrecognized unilateral stenosis of the renal artery]. AB - When patients with functional unilateral renal artery stenosis are treated with an angiotensin I converting enzyme inhibitor (ACE-inhibitor) a risk is present for loss of the function of the affected kidney without clinical symptoms. Renal function should therefore be controlled in these patients before and after initiation of the treatment. Even a slight increase in serum creatinine must be followed by reassessment of the treatment and investigation for renocascular hypertension must be considered. PMID- 2588388 TI - [Tuberous sclerosis]. AB - Tuberous sclerosis (TS) is a congenital disease with hamarthromata, localized in particular to the central nervous system and skin. Other organs such as the heart, kidneys and eyes are, however, frequently involved. The disease is much more common than originally assumed. The most recent investigations show a prevalence of 1:9,704. TS is a dominant hereditary disease but with varying penetration. The frequency of mutation is probably less than previously assumed. The gene for TS is localized to the long arm of chromosome 9 (q34). Prenatal diagnosis is not yet possible. The symptoms and the course of condition depend upon the organ system involved, the age of the patient and of the varying penetration. All patients with TS must be examined with Wood's lamp, and be submitted to sonography of the kidneys, echocardiography, ophthalmic examination and computed tomography of the cerebrum. Treatment is purely symptomatic but surgical intervention may be considered. The present authors recommend that all patients with TS are submitted to the abovementioned examinations once annually with the exception of computed tomography of cerebrum which is undertaken if cerebral involvement is suspected. PMID- 2588389 TI - [An evaluation of ambulatory psychotherapy]. AB - Only few research studies on psychotherapy in Denmark have been published. Our investigation summarizes the results of the psychotherapeutic treatment given 1982-1987 at the Outpatient Clinic for the treatment of Neuroses, Psychiatric Hospital in Aarhus. 45% of the 803 patients who were referred to the clinic commenced psychotherapy. 30% of the patients were students aged 20-39 years. Diagnostically, 60% of the patients had neurotic disturbances, 20% were borderline personality organised and the remainder included patients with higher level personality disturbances and psychotic patients. 85% of the patients were on the waiting list for less than six months. 42% of the men and 52% of the women had more than 25 psychotherapy sessions. 80% had individual psychotherapy. According to the opinions of the psychotherapists, 48% of the male patients and 44% of the female patients gained considerably from the treatment. Those who were helped by the treatment received treatment significantly longer than those in whom the condition did not change or deteriorated. The results of the investigation indicate the need for a prospective qualitative study of the therapeutic alliance, and this investigation is in preparation. PMID- 2588390 TI - [Reproducibility of urine strip reactions in medical patients]. AB - Before a method of investigation is introduced in the daily clinical routine, its reproducibility and correctness must be proved. In the present investigation, the reproducibility of urine stix reactions for glucose, haemoglobin and protein were assessed. The urine stix tests were carried out on freshly voided urine from 30 patients selected at random by three junior nurses with seniorities of one, five and nine years. Complete inter- and intraobserver agreement was found for glukose and haemoglobin whereas the reproducibility for protein was unsatisfactory. PMID- 2588391 TI - [Has Menckes' disease disappeared? Clinical picture and postnatal diagnosis]. AB - Menkes disease is an X-linked recessive disease with an unknown disturbance in the copper-metabolism. We have been diagnosing patients for the last 15 years. Until 1978, six Danish families with Menkes disease were detected. Since 1978 we have only diagnosed one additional patient and one affected fetus in one of the already known families. As the incidence should be about 1 in 45,000 liveborn males, three additional patients should have been seen since 1978. To increase the chances of diagnosing all Danish Menkes patients the clinical symptoms are described. Until now, we have diagnosed 115 Menkes patients and have been in contact with more than 209 Menkes families from many different countries. If we compare the number of inhabitants per Menkes family in different countries, we obtain the following figures, 0.86 x 10(6) inhabitants per Menkes family in Denmark, increasing to 5.21 x 10(6) inhabitants per Menkes family in Italy. Finally some recent experience with copper therapy for treatment of Menkes patients is described. PMID- 2588392 TI - [Transcervical chorion villous biopsy for prenatal diagnosis in the first trimester. A report of the activity during the first 4 years]. AB - Prenatal diagnosis in the first trimester was established in 318 pregnancies at risk by means of transcervical chorion villus sampling (TC-CVS). Criteria for exclusion were discrepancy between the crown-rump length (CRL) and the expected week of gestation, if there was simultaneously insufficient increase in CRL during a week. With the exception of two cases, (0.6%) the specimens of villi obtained were sufficient for diagnostic purposes (mean: 55 mg (8-200 mg]. Twenty five patients underwent terminations of pregnancy on account of the abnormal findings and one for social reasons. The fetal loss following CVS was seven (2.4%). No serious maternal complications occurred. Vaginal bleeding presumably on account of perforation of the placenta by the catheter was seen in 8.5% (27) of the cases and does not appear to influence the continuing pregnancy. The cytogenic results were all based on the direct prepartion method and also on culture technique and these were successful in 100%. Two false positive results (0.6%) were found in the direct preparation but normal findings were obtained on culture. No false negative results were found. Late complications i.e. preterm delivery (4.6%), perinatal loss (0.7%) and neonatal death (0.7%) did not exceed the expected values. The mean birthweight was within the normal range. It is concluded that transcervical CVS with the Trophocan catheter seems to be a safe and easy way to obtain prenatal diagnosis and this could be offered on the same terms as amniocentesis. PMID- 2588393 TI - [Injury patterns in Danish competitive swimming]. AB - A total of 432 Danish competitive swimmers were asked to complete a questionnaire about the epidemiology of injuries sustained during swimming in the season of 1986/1987. Two hundred and sixty-eight (62%) replied. We found a total of 100 injuries in 80 swimmers with an incidence of 0.9 injuries per swimmer per 1,000 hours of swimming, and a point prevalence of 15% on the day of competition. The shoulder, the back and the knee joint were most commonly involved. No particular swimmingstroke was associated with a greater risk of injury. There was, however, a tendency for butterfly swimmers to have more frequent shoulder injuries and for breaststroke swimmers to have more frequent knee-injuries. Medal winners were significantly more frequently injured. Half of the injured swimmers were seen by a doctor. PMID- 2588394 TI - [Can cholesterol be absorbed?]. PMID- 2588395 TI - [The heart society's cholesterol campaign]. PMID- 2588396 TI - [Medical progress and medical ethics]. PMID- 2588397 TI - [Evaluation of suicide in legal accident insurance and private insurance]. AB - The thesis, that suicides are chiefly understood to be terminal stage developments and indemnified through compliance with prerequisites of the insurance law norm, is critically explained with regard to the scientific theoretical evolution. Recent interdisciplinary investigations (epidemiology, statistics, sociology, psychology, psychiatry) as well as the changing approach of a large section of the population towards suicidal behaviour (self determination and the responsibility of the individual, human dignity, breaking away from handed down moral judgements) show that the estimation held with cogency in many quarters with respect to suicide as being a reliable symptom of a disease, cannot be maintained. This result is further supported by the record number of individuals, within the sphere of the private insurance, finding themselves in financial and political "marginal situations" (class and social problems, material safeguard for families and the like) and committing suicide after reasonably pondering their dilemma; a condition which in many aspects comes close to "balance suicide". From an insurance medical angle the relevant statutory provisions and the supreme court jurisdiction of the last years are put forward to the medical experts with the requirements derived hereunder. PMID- 2588399 TI - [Is gambling a disease in the sense of section 169 of the federal insurance law?]. AB - The socalled gambling addiction expresses itself as an exaggerated form of the gambling passion. The act of becoming fixed on or addicted to this (or another) behaviour pattern is always proceded by tentative situations man is succumbing to. The stimulant becomes increasingly more attractive. Regarding such a process, there is not criterion to determine a point when the addiction (which is not linked to a certain matter) becomes a disease. At all events, it is a legal matter to decide whether an extremely defective development that has obviously resulted into social ruin is to be regarded as a disease. The whole range of medical and educational requirements, however, has to be dealt with separately. PMID- 2588398 TI - [Is the suicidal person in the act of suicide in control? Forensic insurance considerations of a new explanatory medical model]. AB - On the basis of extensive psychiatric research into suicide in the Province of Salzburg five stages of suicidal development are initially described: 1) consideration; 2) ambivalence; 3) decision; 4) intention; 5) completion of the action. Whereas in the first three stages both the ability to see reason and to control himself can be unaffected, in the act of self-destruction (stage 4 and 5) the suicide is in principle unable to control himself, whereby the ability to see reason may largely be maintained. This new medical model to explain suicide is discussed with regard to the law of insurance. An attempt is made to provide medical and legal aid for assessors and users of the law. PMID- 2588400 TI - [Fatalities in drug dependent patients: suicide or accident?]. AB - The investigation is based on the evaluation of 87 fatalities arising from drug addiction in autopsy material at the Institute for Forensic Medicine, Tubingen. When considered individually there were 76 cases of intoxication, 10 deaths due to external forces and one death due to natural internal causes as a result of drug abuse. The investigation was mainly concerned with the differentiation between suicide or accidental death in the intoxication group. Amongst the total of 76 cases we found 12 to be indisputable or probable suicides and 44 to be indisputable or probable accidents. The remaining 20 could not be classified with sufficient certainty. With the exception of the existence of a farewell letter there were no single meaningful differentiation criteria. There are indications which in themselves are not strong pointers but which, when considered together, allow a cautious interpretation. Finally the question is discussed as to how far the character changes typical in drug addiction can be explained by a latent suicidal tendency with quoad vitam fatalistic indifference. PMID- 2588401 TI - [Simulated illnesses. Especially Munchausen syndrome]. AB - Factitious disorders pose considerable problems for doctors with respect to diagnosis and therapy. Simulation, the conversion syndrome and the Muenchausen syndrome should be distinguished as individual aspects of the disease. The Muenchausen syndroms has a unfavourable prognosis, as it is difficult to diagnose, in addition to which the patients in question are not approachable for necessary psychiatric treatment. PMID- 2588402 TI - [Blood collection from cadavers]. AB - Withdrawals of blood from corpses are mainly for determinations of blood alcohol but also for toxikological analyses and blood-typing. When the legal conditions for the withdrawals of blood were discussed the technique of withdrawal and the problems of evaluation are debated. Thereby alterations of the samples through putrefaction are especially considered. PMID- 2588403 TI - [Danger of electricity in the bathtub]. AB - A fatal accident, when swimming in a lake, caused by a defective electric main is reported. The medical and technical findings of that accident are discussed as well as the electrophysical prerequisites. PMID- 2588404 TI - [Analysis of permanent accident-induced physical damage based on statistics of the federal insurance organization]. AB - The changes in the occurrence of the accidents are continuously reflected in the computer statistics of the State Insurance Co. Comparing the date from 1970, 1975, 1984, 1986 it is evident the rapid increase in rate and number of the accidents happened at home and the decrease of the accidents in the working places. The pedestrian is run down on the road more often. The rate of the manual workers reaches the 90% among the injured. The most of the accidents at school happen on the physical training and during the break-time. The mortality ratio is 0.78%, the rate of the permanent damages of health 5.72%. 70% of all injuries are caused by mechanical trauma, falling in particular. 30% or higher permanent damage of health caused by accident was found in 3.047 injured persons in the year 1983. 74% male, 26% female, 80% of them were in working age. In 85% of the damaged persons the degree of the P.D.H. was 50% or less, only 15% of them became invalid. The traffic accidents has the leading role in provoking severe P.D.H.-s. In the distribution according the injured part of the body the extremities are leading with 62% of participation, the fractures of the leg, ankle and heel bone in particular. The therapeutic results of this letter group could be improved by better, more careful rehabilitation. PMID- 2588405 TI - [Hearing function in patients with disseminated sclerosis]. AB - The hearing function in 32 patients with various forms of disseminated sclerosis was measured. Their hearing sensitivity, loudness and discrimination as well as spatial hearing and ability to localize sound sources were determined. In the absence of changes in hearing sensitivity, loudness and discrimination all the patients displayed marked disorders or complete loss of their capability to localize sound sources in the vertical plane but retained their capability to localize sound sources in the horizontal plane. Therefore, in contrast to the widely recognized concept that the hearing function in patients with disseminated sclerosis remains intact, spatial hearing impairment should be viewed as a pathognomonic symptom which is very important for diagnosing it at all stages of its development, including the earliest stages. PMID- 2588406 TI - [Reasons for the use of mydocalm in the prevention and treatment of antibiotic induced sensorineural hearing loss]. AB - The applicability of mydocalm for the prevention and therapy of hypoacusis caused by kanamycin, an antibiotic of the aminoglycoside series, was investigated in animal (guinea-pig) experiments. The changes in nucleic acids and nuclear size of the spiral organ were used as parameters. Hearing loss as shown by the lack of Preyer's reflex developed in response to kanamycin injected at a dose of 50 mg/kg/day for 14 days. In the spiral organ nuclei of hair cells were in the state of functional shrinkage. The use of mydocalm at a dose of 12 mg/kg in parallel with or after kanamycin injection nuclei of receptor cells did not shrink, Preyer's reflex did not disappear (in the case of parallel administration of mydocalm and kanamycin) or recovered (in the case of mydocalm administration after kanamycin injection). In summary, mydocalm as a vasoactive and neurotrophic drug can be used for the prophylaxis and therapy of hypoacusis caused by aminoglycoside antibiotics and can be recommended for practical application. PMID- 2588407 TI - [Use of monotreane in the treatment of patients with cochleovestibular disorders]. AB - Patients with cochleovestibular disorders of central and peripheral origin were treated with monothreane (produced by Luitpold Werk, FRG). The drug was given to 70 patients (19 men and 51 women) at the age of 28 to 64 years, 28 patients of which had disorders of peripheral origin and 42 patients disorders of mixed origin. The patients were examined by clinical methods and special tests and hypertension was diagnosed in 32 patients. The therapy yielded good effects in 61 patients: complete recovery of vestibular disorders was seen in 28 patients and relief of headaches in 42 subjects. Side effects were observed in nine patients who showed reduction of perception thresholds which disappeared after drug withdrawal. Monothreane had a beneficial effect on the course of the hypertensive disease. PMID- 2588408 TI - [Effects of furosemide on the excitability of the cerebral cortex]. AB - The effect of furosemide on primary responses of the acoustic brain cortex of unrestrained cats was investigated. The responses were induced by electrical excitation of fibers of the thalamocortical radiation (TCR) and by sound excitation of various intensity and frequency. Furosemide at a dose of 18 mg/kg (intraperitoneally) did not modify primary responses to single stimulation of TCR fibers or their recovery. This diuretic produced an inhibitory effect on primary responses induced by sound excitation. Primary responses that developed in the acoustic cortex to sounds of a frequency of 10,000 Hz showed the highest sensitivity to furosemide. It was found that long-term (10 days) use of furosemide led to enhanced effects of the drug on primary responses to sound excitation. PMID- 2588409 TI - [Electronystagmographic evaluation of changes in vestibular reactions after administration of diverse substances into cerebral ventricles]. AB - Vestibulo-oculomotor reflexes (nystagmus) were recorded by the method of electronystagmography in 33 neurosurgical patients before and after ventriculography. Cerebral ventricles were examined using water soluble compounds (conray, dimeriks, amipaque) in 18 patients or water soluble compounds combined with majodil emulsion in 15 patients. Ventriculography by means of water soluble compounds led to insignificant changes in nystagmic parameters while that by means of X-ray contrasting mixtures caused a frequent and noticeable enhancement of stem vestibular reactions as related to all nystagmic parameters and a significant increase of vestibulo-autonomic reactions. PMID- 2588410 TI - [Morphological features of experimental transient endolymphatic hydrops]. AB - This paper describes a method for simulating transient endolymphatic hydrops based on the generation of vasomotor disorders in the labyrinthine artery area. The method is based on a deep short-term chloroethyl freezing of the lateral surface of the animal surface in the projection of the spinal artery. In histological terms, hydrops is characterized by two factors: vascular lesions (hyperemia of the vascular stripe, venous congestion) and changes in physico chemical parameters of labyrinthine fluids (edema of cell elements of the labyrinth, membrane deformation, precipitation of the granular-reticular residue in the endo- and perilymphatic spaces). This method can be used to study the origin of endolymphatic hydrops during Meniere's disease, to develop new approaches and to give a pathogenetic substantiation of existing approaches to the treatment of Meniere's disease. PMID- 2588411 TI - [Experience in the treatment of vasomotor rhinitis using the method of voluntary arrest of deep breathing]. PMID- 2588412 TI - [NMR tomography in the diagnosis of neoformations of the nasal cavity and paranasal sinuses]. AB - Magnetic and resonance characteristics have been obtained for nasal and paranasal tumors in two groups of patients. Advantages and disadvantages of the NMR- tomography versus computed x-ray tomography are outlined. PMID- 2588413 TI - [Effects of nasal respiration on the thermo-adaptive capacity of the airways]. AB - Respiratory thermography characterizes the role of nasal respiration in the thermo-adaptive function of airways. During nasal inspiration the air temperature in alveoli is 1.5--2.0 degrees C higher than during oral inspiration not only in patients with chronic pulmonary diseases but also in healthy people. In this context, correction of nasal respiration in people with chronic pulmonary diseases should be considered as an efficient factor for preventing exacerbation of the diseases. PMID- 2588414 TI - [Play olfactometry for children]. AB - The method presented includes recording of motor responses to odor stimulation reinforced by electric games. Game olfactometry was performed in 34 young children before and after adenotomy using a specially designed olfactometer which measured an increase in the threshold concentration of odor stimulation. As an olfactory stimulus we used 50% aqueous solution of dimethoxybenzene on identification threshold values. In parallel, we recorded the following physiological parameters: galvanic-skin response, pneumography and ECG. In order to develop a stable reflex, 23 children needed from 7 to 9 reinforcements and 8 children needed from 11 to 12 reinforcements. It was found that the level of identification threshold olfactory stimulation was directly proportional to the number of reinforcements. Our findings allow us to recommend the above method for clinical application. PMID- 2588415 TI - [Use of helium-neon lasers in the treatment of postoperative wounds of the pharynx]. AB - This paper presents the results of treatment of post-operative pharyngeal wounds in 54 tonsillectomized patients (residents of the Far North) using a helium-neon laser. The treatment had a significant analgetic and anti-inflammatory effect which was demonstrated by the so-called swallow test, bar-algisimetry, thermometry of the mucosa of the anterior palatine arches and mandibular area, and cytological examination of the exudate from the tonsillar niches. Application of a low energy helium-neon laser in tonsillectomized patients shortens the therapeutic period by 2 days. PMID- 2588416 TI - [Functional results of tympanoplasty using autologous cartilage]. AB - During 6 years we performed 352 tympanoplasty surgeries and used cartilage plates in 175 cases (49.7%). Total or subtotal defects of the tympanum were found in 83 patients. The tragus or floor of the auricle cartilage was used for surgery. Good morphological results were seen in 93.1% cases by the end of the 1st month and in 92% cases by the end of the 2nd month of observation; good functional results were recorded in 75.4% and 69.1% cases, respectively. Socially adequate hearing improvement was observed in 63.4% patients. In summary, the de novo built system of air conduction becomes functionally operational 9 to 12 months after surgery and remains stable thereafter. PMID- 2588417 TI - [Correlations between changes in hearing and cerebral hemodynamics in patients with chronic alcoholism]. AB - Seventy eight chronic alcoholics, aged 19 to 50 years, were exposed to audiologic and rheoencephalographic examinations. Tone hearing impairment was found in all subjects. The recruitment or greater than normal increment of loudness was primarily identified in patients of Group 1 that comprised those who consumed alcohol from 1 to 10 years. Rheoencephalographic examinations showed decreases of the rheographic index as well as the tone of large and medium caliber arteries in all patients. Group 2 patients who consumed alcohol for more than 10 years displayed greater changes in the vessel tone than Group 1 patients. Analysis of rheoencephalographic waves demonstrated that peripheral and venous tone was decreased in Group 1 patients and increased in Group 2 alcoholics. Visual analysis of rheoencephalographic waves showed lability in the vessel tone of Group 1 patients and a trend for a vessel spasm in Group 2 patients. The results give evidence that Group 1 chronic alcoholics develop toxic lesions of receptors of the hearing organ which is confirmed by the occurrence of recruitment, sound perception impairment, close to normal speech discrimination and insignificant changes in cerebral hemodynamics. Group 2 alcoholics develop marked disorders in cerebral hemodynamics leading to changes in central and intermediate compartments of the hearing organ. PMID- 2588418 TI - [Clinical aspects and treatment of acute epiglottitis in adults]. AB - The data obtained on 25 patients with acute epiglottitis treated in 1986-1988 in an ENT department permitted the conclusion that the treatment of the disease should be based on epiglottitis forms which were dropsical (8 patients), infiltrative (7 patients) and abscess--forming (10 patients). A clinical picture of relevant forms is described. Conservative treatment is sufficient for dropsical forms. Incision of the epiglottis mucosa in the infiltrative form and opening of the abscess in the epiglottis suppuration in combination with infusion and antiinflammatory therapy are obligatory. Life--threatening asphyxia may appear suddenly necessitating urgent intervention and critical care. PMID- 2588419 TI - [Dependence of survival of patients with laryngeal cancer on several clinical and morphological factors characterizing regional metastases]. AB - The frequency of regional metastases as a function of tumor localization in the larynx was identified. The prognostic relevance of various clinical parameters characterizing regional metastases in the vestibular compartment of the larynx was evaluated. The factors that affected the survival rate to the greatest extent were found to be: size and number of regional metastases, their displacement relative to the adjacent anatomical structures, development of contralateral and bilateral metastases, neoformations in the nodes of the lower third of the neck. It was demonstrated that the symbol N was well correlated with the survival rate. The prognostic relevance of lymph node lesions (N+R+) and lymph vessel embolism (N+E+) was ascertained for the first time in the Soviet literature. Both parameters were found to exert a significant effect on the survival rate. The occurrence of one of the morphological parameters dictates the necessity of post operative radiotherapy of the neck region. PMID- 2588420 TI - [Extensive peritonsillar abscess]. PMID- 2588421 TI - [Methodological guidelines in teaching otorhinolaryngology]. PMID- 2588422 TI - [An electrode for recording bioelectrical activity of the cochlea in chronic experiments]. PMID- 2588423 TI - [Myxoma of the laryngopharynx]. PMID- 2588425 TI - [Pneumonia associated with a foreign body in the trachea: an erroneous diagnosis]. PMID- 2588424 TI - [A case of impaired function of the laryngeal muscles in generalized myasthenia]. PMID- 2588426 TI - [Acute suppurative otitis media complicated by extradural abscess, thrombosis of the sigmoid sinus and diffuse purulent meningoencephalitis]. PMID- 2588427 TI - [Congenital laryngotracheoesophageal defect]. PMID- 2588428 TI - [Bioelectrical activity of the cerebral cortex in children with different forms of hypoacusis]. AB - The pattern of bioelectrical activity of the cerebral cortex of 65 children, aged 6 to 15 years, with neurosensory (35 subjects) and conductive (30 children) hypoacusis was investigated. The level of hearing impairment in the patients was different. Electroencephalographic and audiological data were processed by a computer and a statistical (predictable) model was obtained. The model describes the relationship between bioelectrical activity and hearing impairment type and level. It is found that in hypoacusis on a conductive or neurosensory EEG energy spectra and frequencies are different. It is concluded that EEG can be used for assessing the level of rehabilitation of children with marked hypoacusis. PMID- 2588429 TI - [The effect of biotechnological treatment of milk-replacer feeding mixtures on hematologic and biochemical parameters and its utilization in calves]. AB - A trial was performed with cellulase administration (3 cx per g of ingested feed dry matter) to early weaned calves fed minimum amounts of milk replacer (21 kg per milk nutrition period) and sweet (C, D) and sour (A, B) diets. The groups B and D were supplemented with an enzyme till the age of 90 days. The calves were given free choice of COT concentrate mixture, hay and water. Liveweight gains, feed and nutrient intake and health condition of calves were the characteristics investigated in this trial. Hematocrit value, hemoglobin, glucose and urea contents were determined in blood, in blood plasma buffer capacity was investigated. Although the differences in calf performance are not statistically significant, the best growth of calves in the vegetable nutrition period was observed in calves in group D. Nutrient conversion was also higher in calves of group D in the vegetable nutrition period. In conversion of nutrient consumption per 1 kg liveweight gain the difference in the intake of digestible crude protein and starch units between the group of calves fed sweet milk without enzyme addition in the milk nutrient period (A--digestible crude protein 0.40 +/- 0.005; starch units 1.74 +/- 0.008) and group D (sour diet + 3 cx cellulase--digestible crude protein 0.34 +/- 0.007; starch units 1.52 +/- 0.044) was statistically significant (P less than 0.025 and P less than 0.05) in favour of group D. An analysis of the results of hematological and biochemical investigations during the trial demonstrates that the sour diet is better in view of changes in glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588430 TI - [Use of sodium acetate in feed rations in ketotic cows]. AB - On a farm where the ration of cows contained 88.0 g of butyric acid, an experimental group of cows (n = 8), producing milk containing 7.9 mg or more acetone per litre, was studied for 14 days for the effect of a 250 g supplement of sodium acetate to the ration (combined with single i.m. administration of vitamins A, D2 and E) on selected metabolism parameters and on milk production. As distinct from the control group of cows (n = 8) from the same farm which produced milk containing 3.9 mg or less acetone per litre and which were fed without sodium acetone supplements, a tendency of increased alkaemia of the organism was suggested in the experimental cows. This tendency manifested itself during the trial in increased pH values, increased base excess (BE) and standard bicarbonate (SB) in the blood, and in an increase in the pH value and net acido basic secretion in urine. A decrease was recorded in the concentration of the acetone + acetacetic acid sum, the same as beta-hydroxybutyric acid in blood and the sum of acetone and acetacetic acid in milk (P less than 0.01). An insignificant increase of the activity of gammaglutamyl transpeptidase (GMT) was recorded in the blood serum of the experimental cows and a significant increase occurred in the content of potassium (up to P less than 0.01) and urea (up to P less than 0.01) in urine. The supplement of sodium acetate to the feed ration did not influence the degree of ketonuria and the finding of urobilinogen in urine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588431 TI - [Activity of the ovarian follicle system in cows with various puerperal courses]. AB - The presence of the various categories of follicles (less than 0.05; 0.5-1.0; 1.0 1.5; less than 1.5 cm) in the ovaries was examined by palpation, endoscopically and post mortem in cows with a physiological puerperium (n = 5), with puerperal endometritis (n = 5), and with retention of afterbirth (RS, n = 5) from the second to the 20th day post partum (p.p.). The largest proportion (82.6%) of the smallest follicles (less than 0.5 cm) was recorded between the fourth and seventh day p.p. in clinically healthy cows; a marked decrease was then observed until the 15th day p.p. In cows with endometritis the proportion of the smallest follicles was only 60%. The average number of follicles 0.5 to 1.0 cm in size increased 1.6 times in the healthy cows between the 7th and 15th day p.p., but in cows with pathological puerperium their number declined. The largest follicles (greater than 1.5 cm) occurred in the cows with pathological puerperium as late as at the end of the period of study, whereas in healthy cows their occurrence was fairly frequent sooner--between the 8th and 11th day p.p. In all groups of cows the average number of follicles of all size groups declined until the 12th day p.p. which is an indication of the finished first growth wave. Occurrence of the first follicle larger than 1 cm in diameter was observed in 73.3% of cases in the contralateral ovary, opposite to the originally gravid uterine horn. It is assumed that delayed and asynchronous growth of follicles in cows with pathological puerperium is a consequence of disturbed repairing processes of endometrium and of endocrine dysfunction. PMID- 2588432 TI - [Histology of the endometrium in cows in normal and pathologic puerperium]. AB - There were repeated histological bioptic examinations of the endometrium during the period from the second to twentieth day post partum (p.p.) in cows with afterbirth retention (n = 5), with developing puerperal endometritis (n = 5), and with a physiological course of puerperium (n = 5). In cows with a physiological course of puerperium, a finished process of epithelization of endometrium with a morphological and functional consolidation of the epithelium could be observed on the 20th day p.p. In cows with disturbed puerperium, the surface epithelium still exhibited signs of disintegration and a low secretion activity. The endometria of both groups of cows with pathological puerperium had a high degree of infiltration with neutrophil granulocytes: in cows with retained afterbirth this picture was characteristic already the second day p.p. On the other hand, the endometrium of cows with physiological puerperium was characterized by a higher occurrence of folliculoid nodules as early as on the tenth day p.p., and a rapid increase in the number of fat cells and activated histiocytes--macrophages could be observed in the endometrium of these cows between the 15th and 20th day p.p. The dynamics of occurrence of mobile cells in the studied groups of cows confirmed their importance for a physiological course of the restitution of endometrium during the puerperium of cows. PMID- 2588433 TI - [Findings of Yersinia in slaughter pigs, synantropic animals and workers in meat products in a defined region]. AB - In 15 selected stocks in the Strakonice district, 507 slaughter pigs, 708 small terrestric mammals and 110 free-living birds were examined in a two-year period (1986-1987) to study the occurrence of carriers of yersiniae and their elimination. Rectal smears from 243 persons working in livestock production were examined in the same way. Standard bacteriological methods, recent examination procedures (Aulisio et al., 1980; Aldova, 1981) and a diagnostic antiserum (03 IMUNA Sarisske Michalany) were used for the examination. The following results were obtained: In pigs: 1. yersiniae were detected in 65 cases (12.8%); of this, in 31 cases they occurred in the tonsils, in 35 cases in ileum, and twice in the ileocaecal lymph nodes. 2. Epidemiologically significant Y. enterocolitica 4;03 was detected in 28 cases (5.5%); of this, 22 times in the tonsils, 7 times in ileum, and once in the ileocaecal lymph nodes. 3. The seasonal nature of the occurrence of yersiniae was confirmed in 1986, with maxima in winter-spring, but in 1987 their occurrence declined substantially to less than a quarter. In the small mammals, yersiniae were detected 28 times (4%); of this, 7 times in common field mouse, 11 times in common vole, 5 times in house mouse, twice in shrew, once in Apodemus flavicollis, and once in Apodemus sp. 2. Y. enterocolitica 4;03 was detected twice (0.26%), both cases in the house mouse. Other results: 1. In all the 110 free-living birds the examination for yersiniae had a negative result; 2. in the rectal smears of 243 persons employed in livestock production, yersiniae were identified twice (0.8%)--in one case Y. enterocolitica 1, in the other Y. enterocolitica biovars 1 and 2. PMID- 2588434 TI - [The occurrence of Marek's disease in genetically different groups of chickens]. AB - The occurrence of Marek's disease was studied under laboratory conditions in four genetically different groups of chickens (Brown Leghorn, F1 hybrids of the CB x IA inbred lines, pullets of the paternal branch of the grandparent stock of the Hybro meat type, and final hybrids of the White Hisex layer type) after infection with the Georgia strain of Marek's disease (MD) virus, used in two doses (1600 and 16,000 PFU per one bird). MD was diagnosed on the basis of the occurrence of macroscopic tumours; when these tumours were absent in birds which had died within 105 days from infection, the dead bodies were subjected to microscopic examination (peripheral nerves, gonads, skin, bursa of Fabricius, thymus, spleen). The size of the parenterally administered dose of the virus had no significant effect on mortality, occurrence of tumours and the MD virus in any of the groups of chickens tested. However, there was a time shift in the mortality curve in chickens infected with a lower dose. The significantly highest occurrence of MD was recorded in BrL chickens (100%). A somewhat lower occurrence of MD was recorded in the Hisex White chickens (87.8%) and in the CB x IA hybrids (73.8%). However, the dead CB x IA chickens had a higher occurrence of tumours (96.6%) than the Hisex White chickens (77.1%). The lowest MD occurrence was recorded in the pullets of the Hybro meat type (25.5%). The organ most frequently affected by tumours after infection of the birds with the Georgia strain was the liver (24.1%). PMID- 2588435 TI - [Collection of sperm from foxes using electroejaculation under halothane anesthesia]. AB - A method has been developed for the collection of ejaculate from anaesthesized dog foxes. General anaesthesia was produced by inhaling 3 to 5% narcotan mixed with oxygen, the inhalation rate being two litres per minute. An electroejaculator with a bipolar electrode, introduced in the rectum, was used for the electrostimulation of ejaculation. The voltage needed to produce the ejaculation effect and the number of impulses depended on the individuality of the foxes. The average amount of ejaculate per one collection was 0.86 ml, the sperm motility percentage was 74.80% sperm concentration was 270.62 x 10(3) spermatozoa per mm3, and the average pH value was 6.87. PMID- 2588436 TI - Investigation of bovine gut associated lymphoid tissue (GALT) using monoclonal antibodies against bovine lymphocytes. AB - Gut associated lymphoid tissue of the small and large intestine of calves and cows has been compared morphologically and quantitatively using monoclonal antibodies to bovine lymphocytes. B cells were significantly decreased in the ileum of the cow compared to the calf. Significantly increased numbers of T cells were present in cell suspensions of all lymphoid areas of the cow compared to the calf. T lymphocyte subsets were quantified into cryostat sections of lymphoid tissues expressing BoT4, and BoT8 antigens demonstrated increased numbers in follicular and dome areas of the discrete Peyer's patches of the small and large intestine of the cow. BoT4+, BoT8+, and the non-BoT4/BoT8+ T cell subsets were increased in the mucosa of the cow as compared to the calf. Similarities in structure and lymphocyte composition of the discrete Peyer's patches of the small intestine, cecum and colon and isolated single follicles in the large intestine suggest similar functional properties. PMID- 2588437 TI - Ultrastructure and lectin histochemistry of equine cutaneous histiolymphocytic lymphosarcomas. AB - Tissues from subcutaneous lymphosarcomas and regional lymph nodes were examined by light and electron microscopy and by lectin histochemistry. Tumors were composed of two major cell types: small lymphocytes with few organelles and pleomorphic histiocytic cells with undulant surfaces, large numbers of cytoplasmic vacuoles, and many mitochondria with large crystalline inclusions. A large gram-positive coryneform bacterium was isolated from tumor nodules but was not identified morphologically in tumor tissues. Evaluation of sections of tumors with lectins as histochemical probes revealed three staining patterns: 1) lectin labeling histiocytic cells only (wheat germ, succinylated-wheat germ, Phaseolus vulgaris and soybean agglutinins); 2) lectins labeling histiocytic, interstitial and some lymphoid cells (concanavalin A, and Pisum sativum, Lens culinaris, and Ricinus communis I agglutinins); and 3) lectins failing to label any cell (peanut, Sophora japonica, and Ulex europaeus I agglutinins). In the lymph node, macrophages were labeled by lectins of groups 1 and 2; interdigitating reticular cells were labeled by group 2 lectins. Lectin staining of histiocytic cells in tumor tissues suggested that these were reactive cells and that lymphoid cells were the primary neoplastic component. PMID- 2588438 TI - Thyroid neoplasms in a colony of beagle dogs. AB - The histologic, clinicopathologic, and epidemiologic features of spontaneous thyroid neoplasms were evaluated in a control population of Beagle dogs. The mean age of thyroid tumor-bearing dogs (16.2 years) as significantly higher than non tumor-bearing dogs (13.6 years). Thirteen benign and 18 malignant tumors were identified, with the incidence of both tumors increasing rapidly near the mean age of 16.2 years for tumor-bearing dogs. The age-specific incidence of tumors was 1.1% per year at 8 to 12 years, increasing to 4.0% per year by 12 to 15 years and 67% over 17 years of age. Numbers of malignant tumors were greater than benign tumors at an earlier age. Approximately 44% of the malignant tumors metastasized but only 22% resulted in death of the dog. There was no difference in tumor incidence when compared according to sex, if total tumor numbers were considered or if tumors were separated into benign and malignant categories. The age at death of tumor-bearing dogs was not increased significantly by the surgical resection of the thyroid tumors. Of dogs with thyroid tumors, 15% had clinical diagnoses of hypothyroidism, and no dogs with thyroid tumors had diagnoses of hyperthyroidism. PMID- 2588439 TI - Ocular pathology of caprine beta-mannosidosis. PMID- 2588440 TI - Monostotic fibrous dysplasia in a dog. PMID- 2588441 TI - Endometrial carcinoma in a Celebese black macaque (Macaca nigra). PMID- 2588442 TI - Age at death from natural scrapie in a flock of Suffolk sheep. AB - This study deals with natural scrapie in a flock of Suffolk sheep being bred to maximise the incidence of the disease and shows that with succeeding generations the incubation period of the disease became progressively shorter until the flock died out. The most likely explanation for this phenomenon is considered to be an increase in the load of infection. PMID- 2588443 TI - An efficient procedure for manual platelet counting. AB - Blood samples were collected by jugular venipuncture from 15 dairy heifers and the blood platelets were counted by manual methods. The platelets were found to be uniformly distributed across the rows, columns and sides of a Neubauer haemocytometer, and it was shown that counting any 10 squares on either side of the haemocytometer and multiplying by a constant factor would accurately predict the total platelet count. This procedure would greatly reduce the time required to count large numbers of platelets per sample, and reduce errors due to the fatigue associated with counting large numbers of samples. PMID- 2588444 TI - Detection of contagious pustular dermatitis virus of goats in a severe outbreak. PMID- 2588445 TI - Field trial of cypermethrin against lice infestations in goats. PMID- 2588446 TI - Medicines--advice on their use in animals. PMID- 2588447 TI - Behavioural consultants. PMID- 2588449 TI - Research survey. PMID- 2588448 TI - Ivermectin use in collie dogs. PMID- 2588450 TI - Welfare and wellbeing. PMID- 2588451 TI - Sexism in the Mid-West. PMID- 2588452 TI - Food-borne disease incidence rising. PMID- 2588453 TI - Feline anaemia associated with Ehrlichia-like bodies in three domestic short haired cats. AB - Three domestic short-haired cats with a history of anorexia and loss of body condition had high rectal temperatures, and a normocytic, normochromic anaemia. Two of them were also dyspnoeic, and thoracic radiographs revealed a diffuse, unstructured increase in radio-opacity involving all the lung lobes. Examination of Giemsa-stained blood smears and culture of blood monocytes revealed purplish staining intracytoplasmic inclusions, in monocytes and lymphocytes, which occurred either singly or in aggregates. Electron micrographs of a buffy coat smear from one of the cats revealed round intracytoplasmic inclusions, with electron dense and lucid areas morphometrically similar to those found in other members of the genus Ehrlichia. An attempt to culture chlamydia from one of the cats was unsuccessful. The cats were treated successfully, one with tetracycline hydrochloride and the other two with imidocarb dipropionate. PMID- 2588454 TI - Disposition kinetics and urinary excretion of 2-pyridine aldoxime methiodide in sheep. PMID- 2588455 TI - Reduced hatchability associated with engine fumes. PMID- 2588456 TI - Abnormal molar teeth in sheep. PMID- 2588457 TI - Patent ductus arteriosus. PMID- 2588458 TI - Acquired pyloric stenosis. PMID- 2588459 TI - Cough associated with canine vaccination? PMID- 2588460 TI - Second opinions. PMID- 2588461 TI - The effect of stocking rate and parasite control on the performance of replacement beef heifers on pasture. AB - This study was designed to compare the animal production per unit area and per animal at 3 different stocking rates in combination with two deworming programs. Due to drought conditions, fecal egg output, serum pepsinogen levels and herbage larval counts were low throughout the grazing season. The beneficial effects of the strategic deworming program were, however, indicated by lower fecal egg counts and serum pepsinogen levels in the treated groups during most of the grazing season. Differences in weight gain, favoring the treated groups, were also observed and a clear effect of stocking rate was demonstrated. The lowest stocking rate groups continuously had the lowest egg output and serum pepsinogen levels and the highest average weight gain per animal. The experiment also clearly showed that the production per unit area increased with an increase in stocking rate. The medium and high stocking rate groups had a production per unit area exceeding that of the conventional stocking rate group by 15 and 45%, respectively. PMID- 2588462 TI - Host association, on-host longevity and egg production of Ctenocephalides felis felis. AB - Host association, on-host longevity and egg production of Ctenocephalides felis felis (Bouche) were evaluated using fleas from a commercial laboratory colony and first generation, laboratory-reared, native Indiana fleas. Fleas were placed on cats that were declawed, fitted with Elizabethan collars and housed in specially designed metabolic cages. An average of 85% of the female and 58% of the male fleas stayed continuously on the cats for at least 50 days, indicating that the cat flea is a permanent ectoparasite. The maximum longevity of the cat flea was not determined, but it was shown that it can survive and reproduce on the cat for at least 113 days. A female cat flea may produce up to 1745 eggs during a 50-day period. PMID- 2588463 TI - Transmission of Theileria buffeli to cattle by Haemaphysalis bancrofti fed on artificially infected mice. AB - Larval and nymphal Haemaphysalis bancrofti became infected with Theileria buffeli following the intraperitoneal inoculation of infected bovine blood into CBA mice on which they were feeding. Subsequent instars of fed ticks were released on calves and transmitted theileriosis at each of 10 attempts. Suspensions made from ticks moulted in vitro and then incubated for 4 days at 37 degrees C were also infective for calves inoculated subcutaneously. The findings provide a convenient method for infecting ticks with field isolates of Theileria. PMID- 2588464 TI - Experimental production of tick pyaemia. AB - Lambs aged 2 weeks were inoculated with a tick-borne fever (TBF) stabilate on Day 0 and Staphylococcus aureus-contaminated ticks were applied on Day 5. Tick pyaemia was produced experimentally for the first time using Ixodes ricinus as a mechanical vector of S. aureus. Lambs aged 18 weeks were rechallenged with a homologous strain of TBF, and S. aureus-infected ticks applied 5 days later. No significant changes were noted at post-mortem examination. PMID- 2588466 TI - A Neospora-like protozoon found in an aborted bovine placenta. AB - Portions of the placenta and kidneys from a 5-month-old bovine fetus were examined histologically. The placental cotyledonary villi were necrotic and protozoa were found in lesions. The organisms were in trophoblasts, periodic acid Schiff-negative and did not react in an immunoperoxidase test using anti Toxoplasma gondii serum. Individual zoites were approximately 5 x 2 microns and the biggest collection was 45 x 35 microns. The organism in the present case was structurally distinct from Sarcocystis spp. and Toxoplasma gondii, but resembled Neospora caninum. PMID- 2588465 TI - Internal parasites of horses on mixed grassveld and bushveld in Transvaal, Republic of South Africa. AB - Between 1980 and 1982, the gastrointestinal tracts of 17 horses which had been grazing on mixed grassveld at Potchefstroom and bushveld at Onderstepoort in the province of Transvaal, Republic of South Africa, were examined at necropsy and processed for parasite recovery. The large strongyles and their prevalences were as follows: Strongylus vulgaris and associated lesions (88-94%), Strongylus edentatus (24%), Strongylus equinus (30%), Triodontophorus nipponicus (35%) and Craterostomum acuticaudatum (18%). The seven most prevalent and abundant cyathostomes collected were Cylicostephanus longibursatus, Cylicostephanus goldi, Cylicostephanus calicatus, Cylicocyclus nassatus, Cyathostomum catinatum, Cylicostephanus minutus and Cyathostomum coronatum. Gasterophilus intestinalis was the most prevalent and abundant botfly larva recovered. Most of the cyathostome larvae and adults were present during all seasons except winter. The distribution of cyathostome species in the large intestine of the host is discussed. PMID- 2588467 TI - The role of males of the bont tick (Amblyomma hebraeum) in the transmission of Cowdria ruminantium (heartwater). AB - The role of males of the bont tick (Amblyomma hebraeum) in the transmission of Cowdria ruminantium (heartwater) was investigated. Transstadial (nymph to adult) and intrastadial transmission were demonstrated. Males transferred from live or dead hosts to live hosts were shown to transmit C. ruminantium repeatedly. It was concluded that male transmission is of importance in the epidemiology of heartwater. PMID- 2588468 TI - Serodiagnosis of acute toxoplasmosis in macropods. AB - The sera of 34 Australian macropods, the brains of which had been bioassayed for Toxoplasma gondii, were used to establish that a titre greater than 1/32 was significant for a direct agglutination test against toxoplasmosis. In addition, the concentration of 2-mercaptoethanol required to destroy the IgM fraction of macropod serum was confirmed in a modified direct agglutination test. To further validate the tests, the serological responses of three eastern grey kangaroos (Macropus giganteus) dosed orally with T. gondii oocysts and one M. giganteus injected with T. gondii cysts were studied. The tests were then used to investigate a diagnosis of acute toxoplasmosis in four Tasmanian pademelons (Thylogale billardierii) clinically suspected of acquiring toxoplasmosis naturally. One hundred and fifty-one Bennett's wallabies (Macropus rufogriseus rufogriseus) and 85 T. billardierii were also tested to determine the prevalence of acute toxoplasmosis of macropods in the wild. Four percent of M. r. rufogriseus and 1.2% of T. billardierii possessed T. gondii-specific IgM in their sera. PMID- 2588469 TI - Dynamics of elimination of the eggs of Fasciola hepatica (Trematoda, Digenea) in the faeces of cattle in the Porma Basin, Spain. AB - In order to contribute to the knowledge of the epizootiological conditions in which fasciolosis develops in the Leon mountains, the elimination of Fasciola hepatica eggs in 10% of the total number of cattle (1301 samples) at five locations in the Porma river basin was recorded at monthly intervals between March 1986 and March 1987. The parasite was found in cattle [29.5% prevalence, average of 51.6 +/- 4.5 eggs g-1 (e.p.g.) faeces] throughout the year. The main egg elimination period was winter-spring, with maximum prevalence in January and maximum e.p.g. in February-March. Prevalence of infection in cattle generally increased with the host's age, whilst the average e.p.g. varied between different age groups. PMID- 2588470 TI - Effects of exogenous progesterone and/or prolactin on Haemonchus contortus infections in ovariectomized ewes. AB - Reproduction can alter the course of ovine nematodiasis; fecal nematode egg concentrations often increase near lambing and throughout lactation, a phenomenon referred to as the periparturient rise. To identify the host mechanisms that might link these disparate events, i.e. lactation and the fecundity of gastrointestinal trichostrongyles, ovariectomized ewes were injected daily with progesterone and/or prolactin, or saline. Progesterone treatment commenced 20 days before inoculation with Haemonchus contortus and prolactin was administered throughout the 30-day infection period. Ovariectomized ewes receiving prolactin during the experimental infection maintained higher daily fecal egg concentrations than the progesterone, progesterone/prolactin, or the control treatment groups. However, ovariectomized ewes that received 20 days of pre inoculation exposure to progesterone, as well as prolactin during the infection, had greater numbers of nematodes that were larger than the other treatment groups. Thus, the sequential delivery of these hormones that are associated with the reproductive cycle in ewes produced some of the same results that occur during periparturient rise. PMID- 2588471 TI - Efficacy of three broad-spectrum anthelmintics against gastrointestinal nematode infections of goats. AB - Groups of 10 goats, harbouring both naturally acquired and experimental infections of gastrointestinal nematodes, were drenched with either levamisole (5 mg kg-1), albendazole (3.8 mg kg-1) or parbendazole (15 mg kg-1), or remained untreated. Haemonchus contortus was the numerically dominant infection, with Strongyloides papillosus, Trichostrongylus colubriformis and Oesophagostomum columbianum also present. At 5-6 days post-treatment, goats were killed and necropsied. Post-mortem worm counts showed that the reduction in mean total worm burdens was 57.4% in levamisole-treated animals, 71.1% in the albendazole group and 85.1% in the parbendazole group. Reductions for H. contortus were 80.2, 87.9 and 83.9% in the levamisole-, albendazole- and parbendazole-treated groups, respectively. These data indicate that the anthelmintics in question are not being applied at an adequate dose rate for goats, and/or resistance to anthelmintics is occurring in the field in Pernambuco State, northeast Brazil. PMID- 2588472 TI - Effect of a single strategically timed dose of fenbendazole on cow and calf performance. AB - A 168-day study was conducted to evaluate the effect of a strategically timed treatment with fenbendazole on anthelmintic efficacy and performance of beef cows and calves. Eight groups of 10 Angus cow/calf pairs were allotted on 7 May 1987 to eight similarly managed 4.86-ha pastures (bermudagrass/tall fescue) on the basis of cow age, and calf sex and weight. At that time, four groups of cows received a dose of fenbendazole (5 mg kg-1) with their calves receiving fenbendazole at the same dosage 28 days later. Treated calf average daily gain (ADG) was 0.04 kg greater (P less than 0.05) than control calves (0.82 vs. 0.78 kg) during the 168-day study. Treated cow ADG was 0.09 kg greater (P less than 0.05) than control cows (0.40 vs. 0.31 kg). Although there was a reduction (P less than 0.05) in fecal egg counts following treatment of the cows, the numbers of eggs generally were low compared with egg counts of calves. From Day 28 through Day 112 post-treatment, fecal egg counts of treated calves were lower (P less than 0.05) than those of control calves. However, fecal egg counts from treated calves increased post-treatment until there were no differences (P greater than 0.05) between treated and control calves at the end of the study. The pregnancy rate tended to be higher (P = 0.12) for treated cows (98%) than for untreated control cows (75%). The actual calving rate was higher (P = 0.03), for treated cows (90%) than for untreated control cows (68%). Results indicated that a strategic anthelmintic treatment can improve cow and calf performance, but that calves born in late winter or early spring may need more than one therapeutic dose during the nursing period on pasture. PMID- 2588473 TI - Emergence from inhibited development of cyathostome larvae in ponies following failure to remove them by repeated treatments with benzimidazole compounds. AB - The effect of three albendazole treatments at 5-week intervals, beginning at turnout in April, on cyathostome infections in Shetland ponies was compared with the effect of sequential treatments with albendazole, oxfendazole and oxibendazole. The results showed a substantial reduction in faecal egg output after the first albendazole treatment. Since faecal egg counts remained very low, no estimation of the effect of the second treatment was possible. The third treatment with albendazole and oxibendazole was followed by an increase in faecal egg counts to values of greater than 100 eggs g-1 within 4 weeks. A final albendazole treatment in December, 1 week before necropsy, failed to reduce faecal egg counts. These results suggest resistance to albendazole and oxibendazole in the cyathostome populations of the ponies. The increase in faecal egg counts after the third anthelmintic treatment in July occurred, although overwintered pasture infectivity was very low. The most likely explanation for this increase is resumption of the development of worms which overwintered as inhibited larvae in the host. PMID- 2588474 TI - Effects of exercise on skeletal muscle and serum enzyme activities in pigs. AB - In order to determine skeletal muscle and serum enzyme activities following exercise, six adult Landrace pigs were submitted to 10 min running on a treadmill (0.5 m/s, on a 12% gradient) and compared to six controls. Blood samples were obtained just before the exercise, immediately after, and 24 h, 48 h and 144 h after exercise. Muscle biopsies were taken from the longissimus dorsi and biceps femoris 24 h after exercise. Total lactic dehydrogenase (LDH) and LDH isoenzymes in muscle and serum were unchanged. In muscle homogenates, there was no difference in total creatine phosphokinase (CK) activity between the two groups. Total CK activity in the biceps femoris muscle represented only 59% of that observed in the longissimus dorsi muscle. A mean CK-MB value of 2.5% was found in the control group for both muscles but after exercise it was 9.5% (p less than 0.05) for the biceps femoris and 12.2% (p less than 0.01) for the longissimus dorsi muscle. In serum, the total CK (p less than 0.05), CK-MM (p less than 0.05) and CK-BB (p less than 0.05) increased immediately after the exercise, followed by a progressive decrease. PMID- 2588475 TI - The cost of anaplasmosis in the Red River Plains and south-east areas of Louisiana. AB - Losses from morbidity and mortality due to anaplasmosis were assessed in beef and dairy cattle of the Red River Plains and south-east areas of Louisiana. The cost of treatment and prevention of anaplasmosis and losses in milk production and those due to deaths or culling were valued at $0.5 million for the year 1983 in these two areas. The cost of prevention included the use of tetracyclines in feed and salt-mineral supplements, injectable tetracycline, vaccination and an estimated 10% of the cost of insecticidal ear tags, sprays, pour-on applications and dust bags. The remainder of these costs and the total cost of vector control in dairy cattle was attributed to the control of fly annoyance. Treatment costs included veterinary fees and the owner's treatment costs, including labour costs. PMID- 2588476 TI - The effect of management and ecological factors on the epidemiology of anaplasmosis in the Red River Plains and south-east areas of Louisiana. AB - The relationship between clinical anaplasmosis and other disease morbidity, nutritional supplementation, vaccinations, external and internal parasite control, tetracycline supplementation, reproductive management and use of veterinary services was assessed in 320 beef cow-calf herds in the Red River Plains and south-east areas of Louisiana. Data were collected both by mailed questionnaires and by interviews with owners who reported the presence or absence of clinical anaplasmosis. A relationship was found between other disease conditions and anaplasmosis, suggesting disease as a stressor in Anaplasmosis marginale carrier cattle. The herd location of A. marginale seropositive animals and clinical cases of anaplasmosis were related to areas of bottomland hardwood vegetation in which tabanid flies were abundant. This relationship with vegetation was tested by mapping the location of 209 beef and dairy herds which had been serologically tested for anaplasmosis and 256 cases of clinical anaplasmosis in 113 beef and dairy herds. PMID- 2588477 TI - Toxoplasmosis in sheep, goats and cattle in central Ethiopia. AB - In a seroepidemiological survey using an indirect haemagglutination assay, the prevalence rate of toxoplasmosis in central Ethiopia was 22.9% of 899 sheep, 11.6% of 753 goats and 6.6% of 785 cattle. There were high titres of 1:256 or more which suggest current infections. These results indicate that toxoplasmosis may be an important cause of reproductive wastage in small ruminants. The public health significance of this disease is discussed. Improved hygiene and management could reduce the prevalence of the disease. PMID- 2588478 TI - The extraparasitic life cycle of Toxocara vitulorum in the village environment of Sri Lanka. AB - The extraparasitic life cycle of Toxocara vitulorum of buffalo in the villages of Sri Lanka is related to observations on buffalo behaviour, experimental studies on the development and persistence of the eggs in soil and in wallows and the presence of eggs in village locations. Calf faeces on soil were rapidly incorporated by insect activity and the eggs developed only slightly slower than in the laboratory. Some infective eggs persisted 3-4 cm deep for 17 months, finally dying during a prolonged hot, dry period. Eggs in a wallow developed intermittently over 16 months as it was flushed with rain water, and eventually died when the wallow dried out. When infected faeces were placed in water, decomposition caused some material to rise to the surface and eggs developed. In villages, eggs are ubiquitous where young calves are kept but survive best where there is moisture and shade around animal pens and wallows. Cows and calves acquire infection from infective eggs in wallow water, soil and pasture, while calves may also be infected from contamination on the udder and teats of the cow. The larvae resulting from this infection do not mature until the infection is passed to the calf through the milk of the cow. At least 72% of village calves have patent infections and current treatment procedures do not reduce the prevalence. The possibility that T. vitulorum is a cause of human visceral larva migrans is discussed. PMID- 2588479 TI - The kinetic disposition and dosage regimen for carbenicillin in buffalo calves. AB - The distribution half-life, elimination half-life, apparent volume of distribution and total body clearance of carbenicillin in healthy buffalo calves following a single intravenous administration (50 mg/kg) were 0.057 +/- 0.005 h, 1.688 +/- 0.11 h, 0.185 +/- 0.021 L kg-1 and 75.97 +/- 6.519 ml kg-1 h-1 respectively. A satisfactory dosage regimen for carbenicillin in buffalo calves was calculated to be 56 mg/kg followed by 52 mg/kg body weight repeated at 6 h intervals. PMID- 2588481 TI - [From our experience in organizing and conducting military and special training at the N. N. Burdenko Main Military Clinical Hospital]. PMID- 2588480 TI - Bilirubin excretion and bile flow in fed and fasted Brazilian squirrel monkeys (Saimiri sciureus). AB - Fasted Brazilian squirrel monkeys (BrSMs) exhibited slightly higher serum bilirubin levels (0.30 +/- 0.05 mg/dl) than others in the fed state (0.13 +/- 0.01). The mean liver weight was 50% lower following a 22 h fast. The rate of bile flow was unaffected by fasting and averaged 13.8 microliters/min/kg and 47.5 microliters/min/100g liver in six BrSMs. No significant difference in mean bilirubin excretion/min was observed on a body weight basis following fasting. When the mean rate of bilirubin excretion was calculated as a function of liver weight, a two-fold higher rate was present in fasted monkeys, but only at the p = 0.06 level of statistical significance. From data collected in this and earlier studies, it would appear that BrSMs represent the best animals studied to date to serve as experimental controls in comparative studies with Bolivian squirrel monkeys which exhibit a Gilbert-like syndrome. PMID- 2588482 TI - [Characteristics of medical support for foreign servicemen at the military colleges and centers of the Ministry of Defense of the USSR]. PMID- 2588483 TI - [The role and place of pathologic anatomy in the system for training the military physician]. PMID- 2588484 TI - [Eye injuries in explosive mine wounds]. PMID- 2588485 TI - [The human factor in aviation: medical aspects]. PMID- 2588486 TI - [The treatment of eye diseases using the Gamma-G ultrasonic apparatus]. PMID- 2588487 TI - [Chronic gastritis and secretory insufficiency of the stomach]. PMID- 2588488 TI - [Clinical characteristics and variants of the course of peptic ulcer in young people]. PMID- 2588489 TI - [Clinico-anatomic characteristics of laser hemorrhoidectomy]. PMID- 2588490 TI - [Development and characteristics of the course of an isolated urinary syndrome]. PMID- 2588491 TI - [A method for assessing the effectiveness of realizing the requirements for the housing environment for mobile combat materiel]. PMID- 2588492 TI - [Effect of a permanent magnetic field on the function of the endocrine system in animals]. PMID- 2588493 TI - [The pathogenesis of the pain syndrome in pilots on a long flight and its prevention]. PMID- 2588495 TI - [New standards for stocks of medical equipment and stores for routine supply]. PMID- 2588494 TI - [Psychophysiologic disorders in sailors with a history of viral hepatitis A]. PMID- 2588496 TI - [The wound-healing properties of the essential oils of yarrow and Yakut wormwood and khamazulen in napalm burns]. PMID- 2588497 TI - [The Soviet Trade Unions Pavilion--for the benefit of practical public health]. PMID- 2588498 TI - [Current problems in the rehabilitation of alcoholics]. PMID- 2588499 TI - [Qualification characteristics of the military physician]. PMID- 2588500 TI - [The importance of personality and sociopsychological factors in the development of chronic alcoholism]. AB - An analysis of personality and sociopsychological factors in 102 male chronic alcoholism revealed that persons with hysteroid features show a more early alcohol addiction, more rapid formation of symptoms of chronic alcoholism with frequent recurrences and short remissions indicating a more malignant course of the disease. PMID- 2588501 TI - [Contact thermography in the differential diagnosis of benign tumors and cancer of the breast]. AB - Contact thermography was performed in 87 patients with benign and in 75 with cancerous tumours of the breast. Hyperthermia over the tumour is characterized by a 2.2 degrees C and higher increase of the temperature and was registered only in cancer of the breast. Anisothermy of the breast was characterized by a +/- 0.5 degrees C and higher and may be considered as a supplementary diagnostic sign distinguishing cancer of the breast from benign tumours. PMID- 2588502 TI - [Assessment of the health status of preschool children and of its determining factors]. AB - A biomedical examination of preschool children inhabiting an industrial city showing contamination of the atmospheric air allowed to reveal changes of anthropometric data, bradycardia, hypertonia, increase of the minute volume, unfavourable type of mental capacity curve against the background of disturbed metabolic reactions. The above-mentioned changes may be considered as manifestations of the adaptative reaction of the body. It is rational to single out a contingent of high "risk" among children of the first health group. PMID- 2588503 TI - [Thermography in the diagnosis of respiratory organ diseases in coal miners]. AB - A thermographic study of the chest was of importance in the diagnosis and differential diagnosis of pneumoconiosis, chronic dust-induced bronchitis, unspecific pulmonary diseases. This could substitute traditional methods of examination. Results make it possible to recommend the method of thermography in the diagnosis of professional diseases as well as in periodic prophylactic screenings of coal miners. PMID- 2588504 TI - [Gynecologic morbidity among workers at soil and hydroponic hothouses]. AB - Data are analyzed on the frequency of gynecological diseases during the first three years of work in hothouses. There were no differences in the frequency of gynecological diseases, complications of pregnancy course and labour during adaptation to working conditions in the hothouses. In women with a 10-year length of work in hothouses, disorders of the menstrual cycle were more frequent than among women of the administration. PMID- 2588505 TI - [The health status of workers in the manufacture of monomethylaniline semifinished products]. AB - Results of clinico-functional examination in workers engaged in production of monomethylaniline semifinished products revealed a more frequent morbidity of the internal organs, moderate methemoglobinemia, functional changes of the cardio vascular system, disorders of the pulmonary ventilation function, metabolic processes. These data should be considered in therapeutic-prophylactic measures. PMID- 2588506 TI - [Bile acids and bile cholesterol in patients with viral hepatitis A and B]. PMID- 2588507 TI - [Comparative characteristics of immunologic indices in patients with lung abscesses and viral hepatitis]. AB - A study of the immunological status in 52 patients with acute and 20 patients with chronic abscesses of the lungs, 86 patients with viral hepatitis revealed disorders of the immunological reactivity of a quantitative character with monotypic immune response. In autoimmune disorders it is necessary to carry out immunocorrection. In chronic forms immunocorrection should be considered the main treatment method. PMID- 2588508 TI - [The finding of barn mites in human biological media]. PMID- 2588509 TI - [Deontologic problems in patient treatment using physical methods]. PMID- 2588510 TI - [Research trends in the study of pancreatic diseases]. PMID- 2588511 TI - [Experience in the outpatient observation of patients with chronic nonspecific lung diseases at a rural district tuberculosis clinic]. PMID- 2588512 TI - [The effect of riboxin on lipid peroxidation in patients with acute myocardial infarct]. AB - A study of 64 patients with acute myocardial infarction revealed an elevated concentration of peroxidation radicals in the blood, a reduction of the antioxidant system. Three hours after i/v administration of riboxin the content of peroxidation radicals reduced. After discontinuation of intravenous riboxin peroxidation of lipids increased again. PMID- 2588513 TI - [The role of heredity in the development of hypertrophic cardiomyopathy]. PMID- 2588514 TI - [The use of transesophageal electrocardiostimulation in patients with supraventricular tachycardias]. PMID- 2588515 TI - [Correction of dyslipoproteinemia in middle-aged and elderly patients with atherosclerosis using Essentiale in combination with adebit]. AB - A combination of Essentiale and adebit was used in the treatment of 62 patients (age: 60-89 years) with stable stenocardia. Essentiale normalizes the cholesterol metabolism, adebit normalizes the carbohydrate metabolism. Results of the treatment indicate that elderly and old, in particular, showed an improvement of the clinical condition of the disease, normalization of the lipid metabolism. PMID- 2588516 TI - [Oxygen and hemodynamic support for physical load in neurocirculatory dystonia]. AB - Spiroergometric examinations were carried out in 148 students with neurocirculatory dystonia. The adaptation reaction of the cardiorespiratory system to different load strength was studied. The authors used a complex approach with evaluation of the functional parameters of the heart, indices of central hemodynamics and analysis of respiratory gases. As a result of the investigation signs of deadaptation to physical load in neurocirculatory dystonia were revealed. PMID- 2588517 TI - [A comparative evaluation of methods for determining the activity of rheumatic diseases]. AB - The blood concentration of soluble complexes of monomere fibrin (SCMF), fibrin/fibrinogen splitting products (FSP) and sigma-ESB were determined in 11 patients with rheumatic diseases showing an articular syndrome. The authors revealed the diagnostic significance of SCMF in arthritis of any etiology and FSP in rheumatic diseases with systemic manifestations. PMID- 2588518 TI - [Characteristics of the clinical course of Gaucher's disease]. PMID- 2588519 TI - [Difficulties and errors in the differential diagnosis of arterial hypertension]. AB - The authors analyzed 255 case records of patients with symptomatic arterial hypertension treated in the Clinics of the Kiev Research Institute of Cardiology in 1985-1986 with the purpose of differential diagnosis of AH on the out-patient stage. It is concluded that the outpatient level of diagnosis was insufficient mainly due to the subjective character. PMID- 2588520 TI - [An atypical form of chronic myeloleukemia]. PMID- 2588521 TI - [A nontraditional variant for the irradiation of locally disseminated forms of lymphogranulomatosis]. AB - The authors describe immediate results of treatment of 29 patients with lymphogranulomatosis characterized by location above the diaphragm and large volume of tumour masses. Treatment included irradiation against the background of synchronization of cell cycles of the tumour cells and use of metothrexate and folic acid that allowed to reduce early and remote complications of radiation therapy due to reduction of the total radiation doses. PMID- 2588522 TI - [Errors in the diagnosis of malignant neoplasms of the respiratory organs]. AB - Results of 883 autopsies are reported. It was found that the incidence of tumours of the respiratory organs showed an increase as well as of the association of cancer and tuberculosis. They were the main causes of death in antitubercular clinics. It is concluded that errors in the diagnosis of the tumour process are sequels of subjective causes as well as insufficient cancer alertness of phthisiatrists. PMID- 2588524 TI - [Troventol treatment of patients with bronchial asthma and obstructive bronchitis]. PMID- 2588523 TI - [Changes in lymphocytes in acute suppurative-destructive lung diseases]. AB - A study of the content of lymphocytes and their populations, indices of intracellular viral involvement of the lymphocytes in 32 patients with acute purulent-destructive pulmonary diseases and 46 healthy persons revealed an increase of the percent of non-viable lymphocytes containing viral inclusions. Viral involvement of lymphocytes is considered one the leading causes of increased lymphocyte death. PMID- 2588526 TI - [Immunity indices in tuberculosis of the female genital organs]. AB - A study is presented of the cellular and humoral immunity in patients with tuberculosis of the female genital organs. The examination was carried before and after tuberculin provocation (25 and 50 TU). It was established that complex examination of the cellular and humoral immunity in the diagnosis of genital tuberculosis provides essential information on the presence of a specific process, particularly, when it is performed against the background of subcutaneous administration of tuberculin. PMID- 2588525 TI - [Reasons for the late detection of pulmonary tuberculosis]. PMID- 2588527 TI - [Blood coagulation and fibrinolysis in patients with pulmonary tuberculosis suffering from chronic alcoholism]. AB - A study is presented of 63 patients with pulmonary tuberculosis suffering of chronic alcoholism. Examination of the activated recalcification time, thrombin and prothrombin time, plasma fibrinogen level, fibrinolytic activity of the blood, ethanol and protaminsulfate tests, fibrin-stabilizing factor, autocoagulation test revealed in most of these patients significant disorders of the coagulation activity suggesting predisposition to intravascular blood coagulation. PMID- 2588528 TI - [Morphofunctional comparisons in chronic glomerulonephritis]. PMID- 2588529 TI - [Microbiologic indices of the urine in patients with various courses of pyelonephritis]. PMID- 2588530 TI - [Effect of drug preparations in vitro on the morphofunctional status of spermatozoa]. AB - The effect was studied of different drugs (aloe extract, penicillin, vitreous body and lidase) in 20 specimens of the ejaculate with established normozoospermia and in 20 specimens with oligozoospermia, asthenozoospermia and hypozoospermia. Experiments were carried out at +4 degrees C to -38 degrees C, every 2 hours for 72 hours. It was established that depending on the time, temperature and drugs there was an essential difference between the percent of mobility and ultrastructure of spermatozoa. The most favourable effect on spermatozoa was produced by temperature ranges from 11 to 18 degrees C, lidase and penicillin. PMID- 2588531 TI - [Disorders of the hormonal and immune status of patients with newly detected diabetes mellitus]. AB - A study is presented of C-peptide, free and bound insulin, blood serum euglobulins, A, M, G immunoglobulins, circulating immune complexes, insulin antibodies and heterophilic hemagglutinins in 22 patients with newly diagnosed diabetes mellitus and in 29 healthy donors. It was established that at the early stage of diabetes mellitus the peripheral blood showed significant amounts of bound insulin as insulin-anti-insulin antibody complexes. PMID- 2588532 TI - [The kallikrein-kinin, coagulation and fibrinolytic systems of the blood in patients with chronic glomerulonephritis and the hypertension syndrome]. AB - A study of 47 patients with the hypertensive variant of chronic glomerulonephritis revealed a reduction of the functional activity of the kallikrein-kinin, coagulation and fibrinolytic systems of the blood that may be of importance in the genesis of the hypertensive syndrome in patients with chronic glomerulonephritis. A correlation was established between some indices of these systems and the influence was found of the arterial pressure on individual factors of these systems. PMID- 2588533 TI - [Effect of the fatty mass of the body on hemodynamics in men]. AB - The quantity of fatty mass of the body and indices of central hemodynamics were studied in 182 males with a normal, reduced and elevated fat deposition. Persons with a reduced and increased fat content prevailingly showed a hyperkinetic type of circulation, in normal fat content--a eukinetic. As compared with normal, reduced and increased content of fat are characterized by monotypical changes of the central hemodynamics. PMID- 2588534 TI - [Gonadotropins and sex steroid hormones in women with exacerbated duodenal peptic ulcer]. AB - Exacerbation of duodenal ulcer in women of the birth-giving period is characterized by an increase of blood prolactin, progesterone and estradiol that possess a protective action. Simultaneously the concentration of testosterone is elevated which reduces the resistance of the gastroduodenal mucosa. In menopausal women exacerbation of ulcer disease is accompanied by an increase of the FSH level, prolactin, luteinizing hormone and testosterone, significant reduction of estradiol. PMID- 2588535 TI - [The gastrin-producing function of the stomach and intestinal digestion in patients with peptic ulcer]. AB - Assessment of serum gastrin, digestion and absorption of protein, fat 10-15 days after operative treatment in 119 patients with gastric ulcer revealed that independent of the observation time the gastrin level remains low in patients following gastric resection and high following selective proximal vagotomy. The processes of digestion and absorption of proteins, fats are inhibited in the early period after operative intervention with a tendency towards normalization in the remote period. PMID- 2588536 TI - [The vitamin E concentration and lipid peroxidation status of patients with peptic ulcer undergoing laser therapy]. AB - The authors established the necessity that during laser therapy of patients with ulcer disease this treatment should be associated with the use of cholinolytic agents and antioxidants of the alpha-tocopherol type. As the authors' data indicate in ulcer disease a deficit of vitamin E and an enhancement of lipid peroxidation is present. PMID- 2588537 TI - [A foreign body of the stomach simulating a tumor]. PMID- 2588538 TI - [Endoscopy in the diagnosis of perforated gastroduodenal ulcers]. PMID- 2588539 TI - [Nigedase in the combined treatment of patients with chronic pancreatitis and enterocolitis]. AB - The authors examined the efficacy of a new native agent of lipolytic action (nigedase, made in the USSR) used for the treatment of digestive disorders in 62 patients with chronic diseases of the pancreas and enterocolitis. Nigedase should be taken 1-2 tablets daily for 3-4 weeks. By its lipolytic action nigedase is more active than festal. PMID- 2588540 TI - [Use of the early autopsy method for the morphofunctional substantiation of liver failure]. AB - The authors made a biochemical comparative analysis of the blood taken during early autopsies from the portal and hepatic veins and structural-metabolic state of the liver tissue. It is concluded that this analysis is of great importance for morphofunctional substantiation of hepatic insufficiency. PMID- 2588541 TI - [Correction of disorders of bile lipid-mineral composition as a method of preventing cholelithiasis]. AB - A study of 60 patients with biliary tract diseases revealed different disorders of the lipid and mineral composition of bile of monotypical character but different by severity in patients with dyskinesias, cholecystitis and cholelithiasis. Silibor favours normalization of the lipid composition of bile, a dry protein mixture--the mineral composition quadevit--the mineral and lipid composition of bile. PMID- 2588543 TI - [Differential diagnosis in fever of unknown origin]. AB - A study of 156 patients admitted to the clinic with the diagnosis of "fever of unclear genesis" indicates that the most frequent cause of this condition are pathological processes in the abdominal and retroperitoneal space, renal diseases, patients with bacterial endocarditis and connective tissue diseases. Detailed clinical analysis makes it possible mostly to establish a correct diagnosis at early terms of the disease. PMID- 2588542 TI - [Gastroduodenal intubation during submaximal and maximal stimulation with histamine]. AB - A study is presented of 58 patients suffering of chronic gastritis with secretory insufficiency and maintained secretion. On the increase of residual and total gall bladder bile the authors proved the cholecystokinetic effect of histamine which rose with increase of the histamine dose. In chronic gastritis patients with secretory insufficiency hypotension of the gallbladder and dyskinesia of the biliary tract occurred more frequently than in others. PMID- 2588544 TI - [A case of Tietze's syndrome]. PMID- 2588545 TI - [The heterogeneity of late pregnancy toxicosis based on immunologic study data]. AB - The immunological status was studied in 199 pregnant with different degrees of late pregnancy toxicosis. It was found that 20% of women with late pregnancy toxicosis showed an increased content of functional T-suppressors, in 80%- reduced content. Differential diagnosis of these forms of toxicosis allows to institute timely modern immunocorrective treatment. PMID- 2588546 TI - [Disorders of microcirculation and myocardial function in primary pulmonary hypertension and Eisenmenger's syndrome]. AB - Bulboangioscopy, aggregate state of the blood, ultrastructural examination of the microcirculatory bed of the skin, ultrasonic examination of the heart revealed that patients with primary pulmonary hypertension and Eisenmenger's syndrome did not show essential differences in the hemodynamics and blood microcirculation. In the treatment of these patients the stage of chronic circulatory insufficiency, vascular and intravascular disorders of the microcirculation should be considered. PMID- 2588547 TI - [Morphoenzymatic changes of the optic nerve in cardiovascular diseases]. AB - Results are described of a histological and histoenzymatic investigation of visual nerves with a history during life of acute vascular optic neuropathy. It was found that in vascular pathology of the visual nerve due to atherosclerosis, both in the involved and clinically healthy eye different degrees of visual nerve atrophy develop due to sclerotic changes in the blood vessels. The genesis of vascular lesions and atrophy of the visual nerve is to a certain degree determined by immunological changes as evidenced by infiltration of the tissues around the vessels and in the nerve fibers by immunocompetent cells with a pronounced activity of unspecific esterase and acid phosphatase. PMID- 2588548 TI - [The effect of gangliosides on experimental influenza infection]. AB - Experiments in two strains of mice; CBA, susceptible to influenza, and CBAXC57Bl/cXFl, resistant to it, demonstrated stimulation of influenza infection caused by gangliosides. The stimulating effect of gangliosides (GMl, GDla, GTlb) seems to be explained by their insertion into plasma membranes of epithelial cells of the respiratory tract and by an increase, due to it, of the number of superficial virus-specific receptors. PMID- 2588549 TI - [Heterogeneous distribution of influenza A matrix protein in polyacrylamide gel, detected using an immunoblotting method with monoclonal antibodies]. AB - The immune blotting method using monoclonal antibodies to Ml protein showed protein Ml to migrate in several bands in polyacrylamide gel electrophoresis (PGE) of influenza A virus polypeptides. The heterogeneous distribution of Ml protein in PGE is due to the formation of aggregates: dimers, trimers, and polymers of a higher order. The capacity of Ml protein for aggregation is typical not of all influenza virus strains and most likely is not associated with gel overloading. Since dimers and trimers of Ml protein comigrate in the gel with virus-specific proteins such as NP and proteins of a polymerase complex, this circumstance should be take into consideration in using PGE for isolation of pure influenza virus proteins. PMID- 2588550 TI - [Variations in the temperature range for reproduction of virulent and attenuated cold-adapted influenza A viruses]. AB - The informativity of RCT40, RCT37.5, and RCT25 markers for differentiation of wild type strains from ca-recombinants obtained on the basis of ca donors of attenuation was studied. The RCT25 marker and express RCT37.5 marker (determined within 24 hours) were found to be universal characteristics differentiating ca recombinants from virulent viruses. PMID- 2588551 TI - [Indicators of collective immunity to influenza depending on the blood group and sex of the population]. AB - Immunological investigations of the time course of serum anti-HA and anti-NA antibodies against influenza A and B viruses in the female and male population with blood groups 0(I), A(II), B(III), and AB(IV) were carried out for several months. The persons with the blood group AB (IV) were shown to be most sensitive to influenza A and B. They were affected by the epidemic virus earlier and more severely than those with the other blood groups. A special method is proposed for prediction of the etiology of the forthcoming epidemic. A correlation between blood groups and titres of anti-HA but not anti-NA antibodies was observed. The view on the lack of the genetic factor influence on the affliction with influenza and antibody response in persons of different sexes is substantiated. PMID- 2588552 TI - [A comparative analysis of epidemic strains of the influenza A virus (H1N1), isolated in the USSR and Czechoslovakia in 1986]. AB - A comparative study of antigenic and molecular-biological properties of epidemic influenza virus strains isolated in the USSR and CSSR in the autumn-winter, 1986 1987 was carried out and showed that the epidemics in both countries were due to influenza A viruses of H1N1 subtype, antigenically related to the reference A/Taiwan/1/86 and A/Singapore/6/86 strains, which was confirmed by electrophoretic studies. The strains were found to vary in sensitivity to heating and to the inhibitors. PMID- 2588553 TI - [A study of monoclonal antibodies to HBsAg by a method of radioimmunoassay with autoradiographic recording of results]. AB - Radioimmunoassay (RIA) with autoradiographic registration of the results was used to study 11 monoclonal antibodies (MCA) to HBsAg. The MCA were highly specific, stable, had sufficiently high titres in the range of 4 X 10(4) to 6 X 10(5). They were divided into 3 competition groups; a correlation was established between the appurtenance of MCA to a certain competition group, their amount, titre, and activity as "catch" antibody. The a-HBs MCA proved to be of low effectiveness as iodinated indicators of immune complexes. The expedience of using a-HBs MCA and combinations thereof as "catch" antibodies in detection of HBsAg in sera of asymptomatic carriers was shown. The experimental data indicate the advantages of using the autoradiographic variant of RIA both for screening of MCA and for the development on the basis of a-HBs MCA of highly technologic and economic diagnostic systems for HBsAg detection. PMID- 2588554 TI - [Slowly-sedimenting hemagglutinin of the tick-borne encephalitis virus]. AB - Ring-shaped particles of 5-10 mm in diameter considered by research workers to be a slowly-sedimenting hemagglutinin (SSHA) of flaviviruses (an antigen immunologically related to virions) were detected in the precipitation band formed in immunoelectrophoresis by the non-virion ("soluble") antigen but not in the precipitation band formed by the virion antigen. The slowly sedimenting (SS) virions of tick-borne encephalitis virus previously found in a SSHA fraction did not differ in the set of structural proteins from virions of the main population (rapidly sedimenting). It is concluded from the foregoing that the hemagglutinating activity of the SS-structures is realized not by a hypothetic SSHA ("natural" ring-shaped fragment of virion envelope, precursor or a by product of virus morphogenesis, according to other workers) but by SS-virus particles. PMID- 2588555 TI - [Assessment of potential epidemiologic danger of sources of respiratory syncytial infection by biological properties of the pathogen]. AB - Biological properties of 188 strains of respiratory syncytial (RS) virus isolated from 93 institutionalized children during 4 years of observations were correlated with the form and stage of the infectious process, frequency of ARD, and blood group of the children for the evaluation of the epidemiological hazard of sources of RS infection. The degree of virulence of a strain was evaluated by its yields in human embryo lung culture and sensitivity to antibodies (avidity). In clinically manifest forms of RS infection more virulent strains were isolated than in inapparent infections and transitory asymptomatic virus-carrier state. Among the strains derived from children with frequent ARD, highly and moderately virulent strains were prevalent (in 72.7% high and moderate yields in cell culture, and 94.2% low avidity to antibodies) whereas children with rare ARD yielded mainly low virulent strains (70% none or low yields, and 62.5%--highly sensitive to antibodies). The RS virus strains isolated from children with A (II) blood group were found to be less sensitive to antibodies. PMID- 2588556 TI - [Interferons produced by human leukocytes after induction with influenza virus]. AB - Influenza virus induces in human leukocytes the production of 3 types of interferon: 1--acid-labile, produced up to 3 days; 2--acid-stable, produced for 24 hours; 3--acid-stable, produced up to 3 days and showing antiviral activity in heterologous culture of cow embryo lungs alone. The heterogeneity of properties of the 3 interferon types appears to reflect heterogeneity of molecular weights of its components. PMID- 2588558 TI - [Spread of influenza viruses among synanthropic and semisynanthropic birds of the middle Dnieper from the data of serologic studies]. PMID- 2588557 TI - [A study of the aggregate state of isolated hemagglutinin from influenza virus in an aqueous solution by a laser correlation spectroscopy method]. PMID- 2588560 TI - DIC and acute renal failure as a complication of abruptio placentae. AB - Disseminated intravascular coagulopathy (DIC) is not a new concept. Almost 90 years ago De Lee reported a case of fetal coagulation disorder with abruptio placentae and described it as "temporary hemophilia." Disseminated intravascular clotting is the result of a widespread exposure of the circulating blood to procoagulant activity capable of activating fibrinolytic enzyme system converting fibrinogen into the fibrin. Fibrin may in turn cause small blood vessel occlusion resulting in tissue necrosis, and as the phenomenon occurs more often in the glomerular capillaries acute renal failure may ensue. PMID- 2588559 TI - [Detection of delta-antigen in the liver of patients with chronic delta hepatitis]. PMID- 2588561 TI - Laser tumor debulking. AB - When adequate tumor ablation is nonfeasible, debulking has become essential to palliate or to prepare patients for chemotherapy, radiotherapy or definite surgery. The CO2 and Nd:YAG lasers were used to debulk 120 head and neck cases, of which 118 were successfully debulked. The advantages of the laser as a debulker are its facility, rapidity, repeatability, coagulability, atraumaticity, precision, sterilization, and prompt healing; thus, tracheostomy and extended hospitalization were obviated. This paper describes the effectiveness and benefits of the CO2 and Nd:YAG lasers as tumor debulkers. PMID- 2588562 TI - Cholesterol emboli syndrome. AB - The cholesterol emboli syndrome is a disorder caused by showers of microemboli which impact the small arteries. It can occur spontaneously or be precipitated by vascular surgery, arteriography or anticoagulation. The typical patient is a man older than 60 years with risk factors for atherosclerotic disease. The organs most often affected are the kidneys, skin, muscles and abdominal viscera. Common clinical presentations include renal failure and livedo reticularis or gangrene of the toes with intact pulses. Eosinophilia and hypocomplementemia may occur. The syndrome can be fatal or result in end-stage renal disease, but partial recovery can also occur. PMID- 2588563 TI - [Studies on enhancement of nonspecific resistance to infection by leptospiral lipopolysaccharide. II. The mechanisms of the nonspecific protective activity of the LPS]. AB - Leptospiral lipopolysaccharide can enhance the nonspecific resistance of host to infection. By researching its mechanism, we found: (1) The phagocytic function of peritoneal macrophages of guinea pigs was strengthened by E-LPS and L-LPS; (2) L LPS and E-LPS activated peritoneal macrophages of mice then enlarging the cell raji, and increase the quantity and activity of intracellular acid phosphatase. Relatively, the L-LPS might have a greater action in synthesis of the enzyme, while the E-LPS mainly enhanced the activity of the enzyme; (3) L-LPS and E-LPS appeared to be immunomodulant. When they were injected 3d after immunizing the mice with SRBC, immune adjuvant effect developed; however, if the injection of LPS was made 24h prior to the immunization, it would result in immunosuppression. PMID- 2588564 TI - Clinical responses with active specific intralymphatic immunotherapy for cancer- a phase I-II trial. AB - We evaluated the method of active specific intralymphatic immunization to treat cancer in 32 patients with various tumor types as part of a broad-based phase I II evaluation and describe the results of 3 sequential series. In series 1, the patients (n = 13) received 2 or more injections of autologous, cryopreserved, irradiated tumor cells directly into the lymphatic system through the cannulation of a dorsal pedal lymphatic channel. In series 2, the patients (n = 7) received low-dose cyclophosphamide, 300 mg per m2, 3 days before the autologous cell vaccine was administered. Series 3 (12 patients) was similar to series 2 except that the tumor cells were treated with cholesteryl hemisuccinate immediately before irradiation. Patients received from 2 to 6 injections of cells, depending on availability, at 2-week intervals. In all, 91 treatments are evaluated in this study. Clinical responses occurred in 7 of the 32 patients and were seen in all 3 series with about the same frequency. These responses occurred in cases of melanoma, lung cancer, colon cancer, and sarcoma. Regressions occurred in both visceral and subcutaneous sites. There was little toxicity, the chief side effect being local discomfort or inflammation. This experience indicates that active specific intralymphatic immunotherapy is safe, produces antitumor effects, and requires more investigation to increase the frequency and duration of observable tumor regression. PMID- 2588565 TI - Total and high-density lipoprotein cholesterol measurements. Hazards in clinical interpretation. AB - Duplicate plasma specimens from 24 persons were sent to a community hospital, a commercial laboratory, and a university lipid research laboratory at two separate times to assess the intralaboratory and interlaboratory variations of total and high-density cholesterol measurements. For all three laboratories, the 95% confidence limits for the reproducibility of total cholesterol levels are about +/- 5.5%. For high-density lipoprotein (HDL) values, they are +/- 7%, +/- 14.45%, and +/- 9%. Interlaboratory differences for total cholesterol at the 95% confidence level are +/- 7.7% and for HDL +/- 18.4%. Construction of a "cardiac risk ratio" of total to HDL cholesterol levels is subject to confusion because small errors in HDL cholesterol levels produce large errors in the ratio. PMID- 2588566 TI - Shifting sands in science. PMID- 2588567 TI - The clinical dilemma of psychotropic drug use during pregnancy. PMID- 2588568 TI - Regional chemotherapy for hepatic tumors--new hope on the horizon. PMID- 2588569 TI - Systemic lupus erythematosus presenting as hypoglycemia with insulin receptor antibodies. PMID- 2588571 TI - Doctors, patients, and fear. PMID- 2588570 TI - Haloperidol-induced neuroleptic malignant syndrome in a 67-year-old woman with parkinsonism. PMID- 2588572 TI - Psychiatric manifestations of physical illness. PMID- 2588573 TI - 'Minor' can be a source of major debate. PMID- 2588574 TI - Circumcision. PMID- 2588575 TI - The malpractice claims experience of physicians investigated for inappropriate prescribing. AB - Inappropriate prescribing of controlled substances, primarily opiates and benzodiazepines, is the most common complaint brought before the Oregon Board of Medical Examiners. We describe the malpractice claims experience of 120 physicians previously investigated by the Oregon board for inappropriate prescribing. These physicians were matched with a comparison group by age, specialty, and practice location. We found that a mean of one malpractice claim had been filed against each physician in our study, with the specialties of obstetrics and gynecology, neurosurgery, and orthopedics having the most claims. A significantly higher mean number of malpractice claims had been filed against 31 physicians disciplined by the board. Our study suggests a role for state regulatory boards in the malpractice area. We propose that such bodies do practice reviews based on the convergence of two events, a disciplinary action such as those described in this article and the filing of more than one malpractice claim against a physician. Further research is needed on inappropriate prescribing by physicians and its possible association with malpractice. PMID- 2588576 TI - An 80-year-old man with acute abdominal pain. Small bowel obstruction due to midgut volvulus. PMID- 2588577 TI - Death certification. Purposes, procedures, and pitfalls. AB - Completing a death certificate properly and promptly is an important duty for physicians, who must understand how the death certificate is used and be able to recognize and employ the concepts of immediate, underlying, and contributing causes of death. Accurate, concise terminology should be used to give in a logical order a sequence of events leading to death. Avoiding mistakes in death certification helps reduce potential medicolegal problems and provides more meaningful statistics for health care personnel. PMID- 2588578 TI - A travelers' clinic in an academic setting. AB - The Department of Family and Community Medicine at the University of Arizona has operated a travelers' clinic since 1983, staffed primarily by faculty and residents from the sections of preventive medicine, occupational medicine, and family medicine. We describe the clinic experience in providing preventive medical services to international travelers. Summer months are the busiest. Destinations of the travelers show a clear predominance of travel to less developed countries, and this is reflected in the immunizations and prescriptions provided. After their trips, travelers reported a low incidence of diarrhea of generally low severity. The travelers' clinic is also a positive experience for resident physicians who help staff it, particularly those specializing in general preventive medicine. PMID- 2588579 TI - Injuries to search and rescue volunteers. A 30-year experience. PMID- 2588580 TI - Trends in Campylobacter pylori in pediatric and adult antral biopsies. A 5-year retrospective analysis. AB - Campylobacter pylori has been associated with chronic gastritis and antral ulceration in adults and has recently been reported in children with primary antral gastritis and duodenal ulceration. We reviewed all gastric antral biopsy specimens from children (n = 30) and adults (n = 77) over the past 5 years at the University of California, San Francisco. Tissue sections were stained with Giemsa to detect C pylori, and medical histories were obtained by chart review. The prevalence of C pylori in antral biopsy specimens with gastritis increased from 22% during the period 1983 to 1986 to 66% in 1987 (P less than .001). In all specimens showing gastritis, C pylori appeared more frequently in adults (31/67 [46%]) than in children (4/17 [24%]). In cases with primary gastritis, however, the prevalence of C pylori reversed to 57% (4/7) in children versus 49% (31/63) in adults. Most children (10/13) with gastritis and no C pylori had predisposing conditions. Infection with this organism was associated with more active inflammatory changes in adults than in children, but it may contribute to most cases of hitherto-unexplained gastritis in children. Further studies are needed to determine whether the prevalence of C pylori is increasing. PMID- 2588581 TI - Strongyloidiasis associated with human T-cell lymphotropic virus type I infection in a nonendemic area. AB - Concomitant strongyloidiasis and human T-cell lymphotropic virus type I (HTLV-I) infection has been reported from areas in Japan where both organisms are endemic. We present four cases of concomitant infection with these organisms from an area that is not endemic for Strongyloides stercoralis. Three of the four patients had adult T-cell leukemia, an aggressive neoplasm resulting from HTLV-I infection, while the other was an asymptomatic carrier of HTLV-I. Three of the patients had spent their childhoods in an endemic location for both organisms, suggesting an initial infection at that time. Three patients were symptomatic from their parasitism. We conclude that strongyloidiasis may be found in nonendemic locations in patients with either adult T-cell leukemia or an asymptomatic HTLV-I carrier state. Whether infestation with this parasite contributes to the leukemogenesis of HTLV-I, as postulated by others, cannot at this time be determined. PMID- 2588582 TI - Anticoagulation--'sufficient conclusions from insufficient premises'? PMID- 2588583 TI - Alcohol and the cardiovascular system. PMID- 2588584 TI - 'Yewdow'-induced anemia. PMID- 2588585 TI - Neurogenic diabetes insipidus in an initially healthy neonate. PMID- 2588586 TI - Occult retroperitoneal carcinoid tumor with flushing and solitary lung metastasis. PMID- 2588587 TI - The care of asymptomatic HIV-infected patients. PMID- 2588588 TI - Assessing the economic impact of AIDS in local communities. Current and projected costs for San Diego County. AB - The economic cost of the acquired immunodeficiency syndrome (AIDS) in San Diego County, California, is forecast to increase from $103 million in 1986 to between $502 and $743 million in 1991, rising at a minimum average annual rate of 30% after adjusting for inflation. A greater emphasis on outpatient care and the use of new therapies that increase life expectancy by reducing the frequency and severity of morbidity will decrease the future annual cost of treatment but will have a small effect on total economic costs because of substantial foregone earnings by persons with AIDS. Estimating the economic impact of this disease provides valuable information for formulating effective strategies to treat AIDS patients, to provide education for limiting the spread of the human immunodeficiency virus, and to achieve other health objectives. PMID- 2588590 TI - Is academic medicine providing the best patient care? Some personal observations. PMID- 2588589 TI - Diagnostic patterns in hospital use by an urban homeless population. AB - Because patterns of disease and health care system usage by the homeless constitute a neglected area of research in the medical literature, we undertook a retrospective analysis of inpatient records on medically indigent adults, controlling for housing status, to add to the growing body of research in the area of homeless health care. Data on all 4,243 indigent patients admitted over 2 fiscal years (1985 and 1986) under the county medical services program of San Diego County, California, revealed 5.3% (226) to be homeless. The commonest major diagnostic category among the homeless discharges was "diseases and disorders of the skin, subcutaneous tissue, and breast," constituting 21.2% as compared with only 8.7% of the discharge diagnoses for housed indigent persons. Within this major diagnostic category, the predominant diagnosis-related group was cellulitis, accounting for 12.8% of diagnoses in the homeless and only 4.0% of discharge diagnoses in other medically indigent persons. A homeless housing status was also correlated with a higher percentage of discharges with the major diagnostic category of "substance use and substance-induced organic mental disorders" but was negatively correlated with that of "diseases and disorders of the circulatory system." PMID- 2588591 TI - [Do passive smokers have an increased risk of thrombosis?]. AB - In contrast to the proven association between active smoking and vascular injury, as well as hemostatic imbalance, such a relation is not jet proven for passive smoking. Vascular damage induced by smoking, however, can be seen in the materno fetal circulation of smoking mothers, being much more pronounced in the umbilical system than in fetal vessels. These lesions show fast recovery after birth. In non-smokers acute exposure to passive smoke induces a short-lasting activation of platelet function and the prostaglandin system, followed by a quick recovery. Chronic exposure of non-smokers to passive smoke, however, results in changes of these parameters comparable to those seen in smokers, characterized by an activation of platelet function and a decrease in platelet sensitivity to the antiaggregatory prostaglandin I2. These results suggest that in non-smokers with atherogenic risk factors passive smoking may contribute to the incidence of atherosclerosis, as well as acute complications (thrombosis). PMID- 2588592 TI - [10 years' intervention in coronary risk factors in a rural community]. AB - In 1977 a field survey of coronary risk factors was undertaken in a Tyrolean village. All inhabitants aged between 20 and 64 years were investigated for hyper cholesterolaemia, hypertension and smoking. In subsequent years a community intervention programme was developed and implemented in a joint endeavour between the general practitioners of the village and the project leader. After 10 years, in May 1987, a new survey was conducted in the age group 20 to 74 years. The mean values for systolic and diastolic blood pressure as well as the plasma cholesterol level of the original cohort were found to be significantly lower than 10 years previously. There was a substantial, but not significant reduction in the percentage of male smokers in the age group 20 to 64 years, but no change in the percentage of female smokers. PMID- 2588593 TI - [Results of micro(vascular) surgical interventions in vascular-induced disorders of erection]. AB - In 71 patients aged 20 to 65 years who suffered from erectile dysfunction of vascular (mainly arterial and venous) origin, we performed 66 microsurgical vascular reconstructions (12 according to Michal II, 42 using Virag I, 5 using the Hauri modification and 7 according to the author's own method) and 5 operations to reduce venous outflow from the corpora cavernosa. In addition, 6 Virag I redo reconstructions and other secondary interventions in 18 cases were performed as well as (semi-)conservative therapeutic measures were undertaken. Over a mean follow-up period of 35.1 months 46 out of 56 men were again able to have adequate to normal sexual intercourse. The other patients showed only minimal improvement or their condition remained unchanged. No patient's condition was seen to worsen. The main complications were occlusions of the reconstruction and the hypervascularization syndrome of the penis, affecting 13.3% of the arterio-venous anastomoses. This complication, which often occurred many months postoperatively, was always overcome with banding and in some cases by additional venous ligatures so that a functional reconstruction remained in all but one case. In cases of erectile dysfunction of vascular origin, vascular surgery presents the most natural form of therapy and therefore deserves consideration before life-long auto-injection therapy is prescribed for the corpora cavernosa or the implantation of a penis prosthesis is considered. Specific angiological investigation is advisable in all cases in which a four- to six-month course of (semi-)conservative treatment does not bring long-term success. PMID- 2588594 TI - [Endoscopic sclerotherapy of bleeding Mallory-Weiss mucosal tear]. AB - Based on a review of 66 patients with the Mallory-Weiss syndrome, the problems of diagnosis and treatment in general, and the application of sclerotherapy in particular in patients with bleeding tears is discussed. At emergency endoscopy 32 patients (48.4%) had an acute bleeding episode which could be stopped by sclerotherapy in 26 of 27 cases. The importance of control endoscopy after 48 hours and its influence on prognosis are emphasized. PMID- 2588595 TI - [Peptic ulcer with a visible non-bleeding vascular wall--early elective surgery or endoscopic therapy?]. AB - The records of 71 patients with the endoscopic finding of a peptic ulcer with a non-bleeding visible vessel, treated between 1982 and 1987 were retrospectively analysed. 16 patients underwent early surgical treatment (group I), 15 patients were treated conservatively (group II) and 40 patients by endoscopic haemostasis (group III). Recurrent bleeding was observed in 6.25% patients in group I, in 53.3% in group II and in 25% in group III, in which case endoscopy was performed again. The patients with arterial bleeding underwent early elective operation after endoscopic haemostasis. Deaths occurred only in the postoperative period: group I 6.25%, group II 13%, and group III 5%. These findings indicate that primary endoscopic treatment in selected patients leads to results equal to those achieved with early surgery. Conservative therapy cannot, however, be recommended. PMID- 2588596 TI - [Extrathoracic versus transthoracic methods of surgical correction of stenoses and occlusions of the aortic arch branches: a comparison]. AB - 125 reconstructions performed during the years 1968 to 1988 were analysed retrospectively. 81 surgical procedures were extrathoracic (64.8%) and 44 transthoracic (35.2%). The symptoms of the aortic arch branch lesions included subclavian steal syndrome in 67 (53.6%), transient cerebral ischemia in 16 (12.8%), residua of cerebral infarction in 5 (4.0%), monocular ischemic attacks in 16 (12.8%) and ischemic arm symptoms in 27 (21.6%) patients. Surgical repair was achieved by subclavian-carotid transposition in 44 (35.2%), carotid subclavian bypass in 23 (18.4%), carotid-subclavian transposition in 2 (1.6%), endarterectomy of the subclavian artery in 5 (4.0%), carotid-carotid bypass in 3 (2.4%), subclavian-subclavian bypass in 4 (3.2%), aorto-subclavian bypass in 9 (7.2%), endarterectomy of the left subclavian artery in 18 (14.4%) and reconstruction of the innominate artery in 17 (13.6%) patients. 124 patients had complete remission of symptoms or at least showed marked improvement postoperatively. The overall patency rate of the extra- and transthoracic procedures in 85% at an average follow-up of 115 months. The patency rate in the extrathoracic group is 82% and not significantly lower than in the transthoracic group with a patency rate of 89%. PMID- 2588597 TI - [Invagination as a complication of malignant lymphoma]. AB - Benign or malignant neoplasms are usually the underlying pathological factor initiating intussusception in the older child. Two cases of non-Hodgkin lymphoma are reported. The surgical procedure and chemotherapy are discussed. PMID- 2588599 TI - [Results of synthetic ligament augmentation of reconstruction of the anterior cruciate ligament]. PMID- 2588598 TI - [Gastro-pericardial fistula following transthoracic fundoplication]. AB - A gastro-pericardial fistula is a rare complication following repair of a hiatus hernia. Only prompt diagnosis and treatment may prevent the fatal outcome of this condition. PMID- 2588600 TI - [Accidental glycol poisoning]. AB - An acute ethylene glycol intoxication is reported. 100 to 130 ml monoethylene glycol which is used as antifreeze were taken by mistake. On admission to hospital the 41-year-old patient was not remarkable. Despite the lethal dose- according to literature--no renal failure developed by immediate intravenous ethanol therapy. While the patient was given 10 g of ethanol hourly, the serum glycol level decreased steadily (93 mg/dl). After a short oral treatment with 5 to 7 g of ethanol hourly, the serum glycol increased to 350 mg/dl, but could be lowered again--after the reinstitution of the intravenous therapy--to those values recorded before the oral therapy. The level of blood ethanol differed between 2.41 and 0.01 mg/l. The creatinine clearance was normal and the serum electrolytes could be kept in the normal range with adequate compensation despite of the polyuria of 13.81/24 h. It is known that even a low ethanol level inhibits the enzymic metabolism of ethylene glycol by ethanol dehydrogenase and prevents the formation of toxic metabolites. The patient luckily had already consumed about 40 g of alcohol (2 bottles of beer), so that an ethanol level existed already before this intoxication. From this case report one could conclude, that the parenterally given ethanol influences the serum glycol level far better than the orally given especially in case it is not more than 7 g/h. If glycol intoxication is sure, hemodialysis is--despite this especially good course of conservative treatment--the more efficient and quicker method because of its good ability of elimination. PMID- 2588601 TI - [Febrile convulsions]. PMID- 2588602 TI - [Causes and diagnosis of short stature]. PMID- 2588603 TI - [Roentgen studies in children: restricted indications due to great radiation sensitivity]. PMID- 2588605 TI - [Congenital heart defects]. PMID- 2588604 TI - [Treatment of burns in children]. PMID- 2588606 TI - [Sudden infant death]. PMID- 2588608 TI - [Juvenile chronic arthritis]. PMID- 2588607 TI - [Urinary tract infection]. PMID- 2588609 TI - [Treatment of internal hydrocephalus]. PMID- 2588610 TI - [Family therapy]. PMID- 2588613 TI - [Blood gases and the small airways]. PMID- 2588612 TI - [Workshop 1988. The Working Group on Clinical Respiratory Physiology of the Austrian Society for Lung Diseases and Tuberculosis. Graz, 13-15 October 1988]. PMID- 2588611 TI - [Pediatric phimosis]. PMID- 2588614 TI - ["Small airways disease--an erroneous expression"]. PMID- 2588615 TI - [Inspiratory respiratory muscle strength in relation to actual intrathoracic gas volumes]. PMID- 2588616 TI - [The informative value of surface electromyography of respiratory muscles]. PMID- 2588617 TI - [Expiratory bronchial collapse--a specific aspect of pulmonary emphysema?]. PMID- 2588618 TI - [Ointments for collecting blood gas samples from the external ear]. PMID- 2588619 TI - [The Pneumobil as an instrument for determining scientifically relevant data]. PMID- 2588620 TI - [The Pneumobile as an instrument for determining screening data]. PMID- 2588621 TI - [Diagnosis of lung function in a peripheral hospital, electronic data processing assisted documentation and statistical evaluation]. PMID- 2588622 TI - Prediction values for FVC and FEV1 in adult Dalmatian population (Croatia, Yugoslavia). PMID- 2588623 TI - [The status of standardization of oscillatory parameters for assessment of respiratory technic]. PMID- 2588624 TI - [Bronchial provocation: cold air or cold water?]. PMID- 2588626 TI - [Nonspecific bronchial provocation: a comparison of 2 methods]. PMID- 2588625 TI - [Provocation by cold air hyperventilation for measuring nonspecific bronchial reactivity in children--the normal range for a spectrum of variable lung function parameters]. PMID- 2588627 TI - [Do Austrian normal values correspond to general practice? Results of an epidemiologic study]. PMID- 2588628 TI - [Quantification of the allergen specific provocation test]. PMID- 2588629 TI - [Air pollutants and bronchial reactivity in primary school children 1]. PMID- 2588630 TI - [Bronchial asthma and gastroesophageal reflux]. PMID- 2588631 TI - [Nonspecific reactivity of former pediatric patients with asthma in clinical remission]. PMID- 2588632 TI - [Ambulatory pulse oximetry in patients with stress hypertension]. PMID- 2588633 TI - [Measuring ciliary frequency: modification of frequency by beta-2-adrenergic drugs and calcium antagonists]. PMID- 2588634 TI - [Struma--goiter--lung function]. PMID- 2588635 TI - [Erythropoietin therapy in renal anemia. Effect on ergospirometry performance parameters]. PMID- 2588636 TI - [Physiologic respiratory parameters in erythropoietin treatment of patients with chronic renal failure]. PMID- 2588637 TI - [Fourier analysis of mouth pressure oscillation during expiratory airflow interruption--on measuring airway resistance using the interruption method]. PMID- 2588638 TI - [Postoperative behavior of pulmonary artery pressure and right ventricular remodeling following orthotopic heart transplantation]. PMID- 2588639 TI - [The patient education and information system of the "Bad Reichenhaller Model"]. PMID- 2588641 TI - [Reliability of peak flow measurement using the mini-Wright Peak Flow Meter]. PMID- 2588640 TI - [A pilot study for evaluating patient education with regard to asthma, bronchitis and emphysema supported by the Bad Reichenhaller Research Institute for Diseases of the Respiratory Tract]. PMID- 2588642 TI - [Progressive exercise dyspnea. Sarcoidosis--emphysema?]. PMID- 2588643 TI - [Functional diagnosis of the nose]. PMID- 2588644 TI - [The role of allergy within the scope of rhinosinusitis]. PMID- 2588645 TI - [An unusual right heart and chronic respiratory flow obstruction]. PMID- 2588646 TI - [Immunology and immunopathology of the nasal mucosa]. PMID- 2588647 TI - [Morphology of the small airways]. PMID- 2588648 TI - HIV among pregnant women: north central Wisconsin. AB - The incidence of infection by the human immunodeficiency virus (HIV) among pregnant women in north central Wisconsin is unknown. We devised and used an anonymous screening protocol to determine both the incidence of HIV infection and the rate of infection spread in this population. Our data demonstrate an extremely low incidence of HIV infection. Further, over the time periods studied, no clear evidence of an increase in the incidence of this severe infection could be demonstrated. PMID- 2588649 TI - Chlamydia in pregnant women: southeastern Wisconsin. AB - Three hundred forty-two pregnant women were screened for the presence of Chlamydia trachomatis in the endocervix using a direct fluorescent antibody test (MicroTrak, Syva Co.). The prevalence of C trachomatis infection was 11.7% in our urban, non-inner-city, family practice center. Single marital status was significantly associated with C trachomatis infection, but obstetrical factors were similar in patients with and without positive chlamydial smears. The use of non-culture techniques to screen community populations of pregnant women for C trachomatis is discussed. PMID- 2588650 TI - Ethylene glycol poisoning. AB - Seven men with ethylene glycol poisoning were treated at our institution during a ten-year period. Six patients survived. Ethylene glycol levels on admission did not directly correlate with the severity of metabolic abnormalities or subsequent complications. The timing of the patients' admissions altered the clinical picture and results of therapy. Patients who came to our facility later than 12 to 24 hours after ingestion had established renal failure and required prolonged hospitalization. We were able to prevent renal failure in the one patient started on dialysis less than 23 hours after ingestion. Our patients exhibited the metabolic, CNS, cardiopulmonary and renal manifestations of ethylene glycol poisoning. PMID- 2588651 TI - A peer review review. AB - Although peer reviewer has faced many legal challenges, some protection is available to peer reviewers through state and federal law. Peer reviewers must follow specific guidelines provided by these laws to maintain this protection. This article outlined the most prominent protection currently available as well as the corollary duties and requirements by which the peer reviewers must abide. PMID- 2588652 TI - The case of nurse Rival and Dr Cutter. PMID- 2588654 TI - Our challenge is great. PMID- 2588653 TI - Mammography guidelines and practices in Wisconsin. PMID- 2588655 TI - HMO financial reports. PMID- 2588656 TI - Breast cancer detection awareness project in Wisconsin: 1987-1988. AB - In May 1987 and 1988, the American Cancer Society (ACS) sponsored Breast Cancer Detection Awareness (BCDA) programs throughout Wisconsin. These programs were made possible by the cooperative efforts of many ACS volunteers, hospitals, clinics, and physicians. The Wisconsin Radiological Society and the Division of Health were also involved in the planning efforts. In 1987, a total of 10,207 women were screened at 100 facilities, and 75 carcinomas were detected. In 1988, of 8,802 women screened at 102 facilities, 52 carcinomas were detected. PMID- 2588657 TI - Nursing: a new tomorrow. PMID- 2588659 TI - Impact of nutrition on health and disease. PMID- 2588658 TI - The 1980's--a decade not to be repeated. PMID- 2588660 TI - Chlorophyll derivatives--a new photosensitizer for photodynamic therapy of cancer in mice. AB - The in vivo photosensitizing efficacy of chlorophyll derivatives (CpD), which had been developed as a new photosensitizer, was compared with that of hematoporphyrin derivatives (HpD). A murine tumor model implanted subcutaneously with S-180 cells on the abdomen was used. The CpD or HpD was administered by intratumoral injection, and light of appropriate wavelength was irradiated on the tumor areas for 10 minutes at 1h and 24h or 24h and 48h after the injection of photosensitizer. When CpD was injected, the early irradiation group (1h and 24h) showed a 100% tumor cure rate; however, the late irradiation group (24h and 48h) showed a 60% tumor cure rate (p less than 0.01). This showed that the early irradiation with light after injection of CpD was an important factor for obtaining better results. With HpD, there was no difference in tumor cure rate between early (1h and 24h, 80%) and late irradiation (24h and 48h, 80%) groups. Thus, in early irradiation groups, the tumor cure rate using CpD (100%) was superior to that of HpD (80%) (p less than 0.05). However, in late irradiation groups, the tumor cure rate using CpD (60%) was inferior to that of HpD (80%), but this difference was not statistically significant (p greater than 0.1). Pathologic sections of these tumors were made before treatment and 48h and 3 weeks after treatment. These showed geographic necrosis at 48h after treatment and no viable tumor tissue at 3 weeks after treatment. Our results showed that CpD was as effective as HpD as a photosensitizer for in vivo photodynamic therapy. PMID- 2588661 TI - Anticancer effect of liposome incorporated with methotrexate and antibody against tumor specific surface antigen of rat hepatoma. AB - antibody against tumor specific surface membrane protein was produced by immunizing a New Zealand White rabbit with antigen (66 kDa) prepared from the plasma membrane of rat hepatoma induced by feeding a diet containing 3'-methyl-4 dimethylaminoazobenzene, and was purified by protein A-Sepharose 6MB affinity chromatography. The purified antibody was incorporated into liposomes by a reverse phase evaporation vesicle method in order to prepare a tumor specific anticancer drug carrier. The effect of the antibody against tumor specific antigen was evaluated by comparing the inhibition of DNA synthesis in hepatoma cells with different preparations of methotrexate. Methotrexate encapsulated into liposome showed a stronger inhibitory effect on DNA synthesis (1.4-1.7 times) than free methotrexate. Liposomes having the antibody showed stronger inhibitory effect (3.1 times) on DNA synthesis than free methotrexate group in hepatic nodular area. From these results, it is concluded that tumor specific antibody inserted into liposomal membrane would be recognized by surface antigens which were expressed on the plasma surface membrane of rat hepatoma cells and thereby increase the carrying efficiency of drugs to the target cells. This could be useful in cancer chemotherapy. PMID- 2588662 TI - Incidence and survival of cancer in Kangwha County (1983-1987). AB - To measure incidence and survival rates of cancer in Kangwha County, 663 cancer patients registered in the Kangwha County Cancer Registry Program for the past 5 years (1983-1987) were analyzed. The average annual cancer incidence rate per 100,000 population was 183.0 in males and 99.5 in females. The common cancers were stomach (37.3%), lung (14.8%), and liver cancer (11.1%) in males and stomach (25.6%), cervix uteri (20.9%), and liver cancer (9.7%) in females. The median survival times of all cancer patients after diagnosis and onset of the first symptom were 8.4 +/- 0.8 months and 15.0 +/- 1.1 months respectively. Female cancer patients survived significantly longer than male cancer patients. The median survival times of the stomach, lung, and liver cancer in males were 7.7 +/ 0.9, 4.9 +/- 0.9, and 2.3 +/- 0.4 months respectively. In females, the median survival times of the stomach and liver cancer patients were 9.2 +/- 1.5 and 2.5 +/- 0.5 months. The 5 year survival rate of cervical cancer was 67.1%. Those cancer patients who received anticancer therapy survived significantly longer than cancer patients without treatment. PMID- 2588663 TI - Patterns of mental disorders among the elderly in a Korean rural community. AB - This study reports the overall prevalence of cognitive impairment and other mental dysfunctions. In Kangwha County, Korea, noninstitutionalized persons aged 65 and older, selected by a stratified two-stage cluster sampling, were interviewed by trained lay interviewers using the Korean version of Older Americans Resources and Services (K-OARS) and Mini-Mental Status Examination (MMSE). Overall, 17% of the population had mild cognitive impairment and 3% had severe cognitive impairment. Self-reports, self-ratings and interviewer ratings of various mental problems and symptoms included in the questionnaire were investigated as variables. Differences in the prevalence rate of various mental problems and symptoms according to a set of demographic variables were examined. PMID- 2588664 TI - Relationship between the sphericity of femoral head-acetabulum and the low incidence of primary osteoarthritis of the hip joint in Koreans. AB - I examined the sphericity and the congruity of the femoral head and the acetabulum in 172 Korean fetuses and in 655 Korean adults. I found that Korean fetal acetabuli and femoral heads are spherical and that the proportion of the head contained in the acetabulum remains constant and congruous throughout the fetal life. Adult actabuli and femoral heads are also spherical in both gender and are there are no visible changes in the shape of the acetabuli and the femoral heads with respect to age. No evidence was found that the congruity of the hip joint is a cause of osteoarthritis of the hip joint. CLINICAL RELEVANCE: Stable hip joints at the time of birth provide an explantation for the low incidence of congenital dislocation of the hip joint in Koreans. The spherical femoral head and acetabulum (congruous hip joint) seem to be a contributing factor to the low incidence of primary osteoarthritis of the hip in Koreans. PMID- 2588665 TI - Risk factors of ischemic brain stroke in Korean diabetic patients--a retrospective study. AB - In order to investigate the risk factors of ischemic brain stroke (IBS) in diabetic patients, we analyzed 416 cases selected from 6239 diabetic patients admitted to Severance Hospital from Jan. 1983 to Dec 1987. Two hundred and eight cases had IBS. The other 208 cases without IBS were selected as a control group by a stratified random sampling method. The two groups were compared using various clinical characteristics of diabetes mellitus (DM) and known risk factors of IBS. In diabetics with IBS, the duration of DM was longer (9.2 +/- 7.1 years), hypertension was more frequently associated (68.2%) and the serum cholesterol level was higher (213.0 +/- 55.2 mg/dl) than in diabetics without IBS (7.6 +/- 7.1 years, 32.1% and 192.1 +/- 44.8 mg/dl, respectively). By means of Stepwise Logistic Regression Analysis (SLRA), it was found that the strong risk factors were hypertension and serum cholesterol level. The serum triglyceride level, type of DM and response to diabetes treatment were also thought to be risk factors of IBS by the retrial of SLRA of residuals after exclusion of hypertension and serum cholesterol level. IBS was not significantly related to the duration of DM, fasting blood glucose level, body weight, glycosylated hemoglobin value, and serum high-density lipoprotein-cholesterol level. PMID- 2588666 TI - Aspergillosis of the paranasal sinuses--diagnostic significance of the computed tomography. AB - Aspergillosis of the paranasal sinuses appears to be relatively rare in occurrence, but there is a growing incidence of it in accordance with the increasing use of antibiotics, steroid hormones, anticancer drugs, and radiation therapy. We have seen 15 cases of aspergillosis of the paranasal sinuses in which computed tomography (CT) was helpful for diagnosis. The characteristic feature of CT findings was the intermixture of high and low density areas in the affected paranasal sinuses, apparently caused by increased X-ray absorption due to calcification. These findings indicate that CT is useful in the preoperative diagnosis of aspergillosis of the paranasal sinuses. PMID- 2588667 TI - Occupational asthma and IgE antibodies to reactive dyes. AB - Reactive dyes have been widely used in recent years. This paper reports nine cases of immediate type occupational asthma to reactive dyes in one dye industry. All patients had had asthmatic symptoms, four had had rhinitis and they had worked for 6 to 25 months. Skin prick tests with reactive dyes were positive and bronchoprovocation tests also produced immediate or dual types of bronchoconstriction. We used the radioallergosorbent test (RAST) technique with nitrocellulose filter paper as a solid phase to detect specific IgE to four reactive dye-human serum albumin conjugates. High specific IgE binding was found in eight asthmatic workers compared with 13 negative controls. The RAST inhibition test revealed that there was no immunological cross-reactivity between 4 reactive dyes. These results suggested that the mechanism of their asthmatic symptoms was immunological, mostly an IgE-mediate reaction. PMID- 2588668 TI - CT findings of the nose and paranasal sinuses in chromium intoxication. AB - We performed computed tomography (CT) of the nose and paranasal sinuses in 21 patients with chromium induced septal perforation or thinning. Twenty patients showed various magnitudes of septal perforation. Twelve of 20 had perforation at the mid portion of the cartilaginous nasal septum. One patient had a sheet-like thinning of septal cartilage. Sixteen patients had mucosal thinning of the nasal conchas. In most cases, unilateral involvement of the inferior concha was seen. Eleven of 21 cases showed paranasal sinus mucosal thickening and one patient had a cyst or polyp in the sinus cavity. The main finding was nodular thickening of mucosa. Septal perforation by inhalation of chromic acid was located in the cartilaginous septum and there was no destruction of the bony septum and wall of the sinuses. PMID- 2588669 TI - Two cases of anterior choroidal artery territory infarction. AB - Occlusion of the anterior choroidal artery (AChA) can cause infarction in the posterior limb of the internal capsule. Infarction is less frequently observed in the thalamus, midbrain, temporal lobe, and lateral geniculate body (LGB) territories of the AChA. The most common clinical finding is hemiparesis. Hemianesthesia may be severe at onset but is usually transient. Homonymous hemianopia, upper-quadrant anopia, or upper- and lower-quadrant sector anopia can be present. Occasionally these patients are reported to have transient abnormalities of higher cortical function. The most common stroke mechanism is known to be small-vessel occlusive disease, predominantly found in hypertensive and diabetic patients. Vasospasm due to ruptured aneurysm or intraoperative mechanical manipulation, and cardiac origin the AChA territory. The infarct lesion is usually recognized and diagnosed by computed tomography. The best treatment is still unknown. PMID- 2588670 TI - [Perioperative prevention of infection with chloramphenicol]. PMID- 2588671 TI - [The prevalence of chronic medical disorders in young workers from the occupational medicine viewpoint]. PMID- 2588672 TI - [German AIDS congress, Berlin (West), 23 to 24 January 1989]. PMID- 2588673 TI - [Principles and experiences with comprehensive management strategies of patients with alcohol abuse and dependence]. PMID- 2588674 TI - [A health record for every citizen--a missed chance or challenge?]. PMID- 2588675 TI - [Diagnostic procedures in disseminated lung diseases]. PMID- 2588676 TI - [Purulent meningitis of rhinogenic or otogenic origin--a contribution to the clinical problem]. PMID- 2588677 TI - [The development and growth of our public health]. PMID- 2588678 TI - [Is psychotherapy effective?]. PMID- 2588679 TI - [Dynamic group psychotherapy and individual psychotherapy reflecting the success of treatment]. PMID- 2588680 TI - [In what way is the physician impeded in the psychological guidance of the patient?]. PMID- 2588681 TI - [The value of expert assessment of disability in neuroses]. PMID- 2588682 TI - [Long-term study of the effectiveness of psychotherapy procedures in the treatment of early forms of primary arterial hypertension in a general occupational medicine practice]. PMID- 2588684 TI - [Medical psychology and the physician's ethics]. PMID- 2588683 TI - [Responsibilities and functions of psychotherapy and medical psychology in the development of comprehensive biosocial thinking in medicine]. PMID- 2588685 TI - [15 years' inpatient psychotherapy at the Ballenstedt Lung Clinic]. PMID- 2588687 TI - [Peculiarities of the development and course of pulmonary hypertension in patients with chronic obstructive bronchitis]. AB - Clinical and functional characteristics of chronic obstructive bronchitis can be useful for diagnostics of pulmonary hypertension. Development of pulmonary hypertension shows 3 stages: latent, transitory and stable phase. PMID- 2588686 TI - Effect of intracerebrally injected aminophylline, vinpocetinum, vasoactive intestinal peptide and onion extract on breathing pattern of rats. AB - Aminophylline or VIP (Vasoactive Intestinal Peptide) given ip. or iv. have marked bronchodilatory effects. The onion extracts protect guinea pigs as well as human patients against allergen-induced bronchial spasms (Dorsch et al.). Recently it has been shown that lipophilic components of onions seem to be responsible for the antiasthmatic effects. The purpose of this study was to investigate the effect of intracerebrally injected aminophylline (3 microM), Vinpocetinum (0.1 mg/kg), VIP (5 micrograms) and onion oils (30 microliters of extracts) on the respiratory center and on the resistance of lower airways of rats. The following respiratory parameters were evaluated: respiratory rate (RR), tidal volume (VT), mean inspiratory flow (Vin), respiratory minute volume (VE), and dynamic lung resistance (R). Respiratory rate was increased and values of all the other parameters were decreased after aminophylline treatment. VIP increased the tidal volume, minute ventilation and the respiratory drive. After injection of onion extracts the respiratory rate and the dynamic lung resistance decreased, but the tidal volume increased. The beneficial effects of onion oil are manifested not only peripherally acting on bronchial smooth muscle but via the reflexogenic pathways. PMID- 2588688 TI - [A model of the isolated blood perfused lung of rats in testing hypoxic pulmonary vasoconstriction]. AB - Comparing two variants of models (in situ, ex situ) of the isolated blood perfused rat lung for measurement of the hypoxic pulmonary vasoconstriction the in situ preparation gave better results. The optimal severity of hypoxia was 2% O2 in intervals (hypoxia and normoxia, respectively) of seven minutes. The model works sufficiently for two hours. PMID- 2588689 TI - [Determination of individual lipid parameters in non-chylous pleural effusions]. AB - Levels of total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol were measured in the pleural effusions and the corresponding serum from 52 patients suffering from non-chylous pleural effusions with different genesis. Significantly higher concentrations of lipids were found in exudates in comparison to transudates. The highest levels of total cholesterol and triglycerides were found in effusions with malignant and pneumonia genesis. It was additionally observed that higher than average values were found for HDL cholesterol in patients with malignant diseases and for LDL-cholesterol in patients with pneumonia. Transudate effusions from patients with heart insufficiency and nephrotic syndrome had significantly lower levels of cholesterol and triglycerides. We were unable to establish a relationship between levels in pleural fluid and serum. PMID- 2588690 TI - [The value of lung perfusion scintigraphy in radiation pneumonitis in comparison with the diffusing capacity DLCO]. AB - The value of lung perfusion scintigraphy (Tc99m) and lung diffusing capacity are compared with references to early detection of radiogenic pneumonitis. Perfusion scintigraphy completed by diffusing capacity is excellent suitable for early detection. Risk cases are recognized up to 40 days earlier than by X-ray. Severity of radiogenic pneumonitis can be diminished remarkable by prevention therapy. PMID- 2588691 TI - [Late results of resection treatment of bronchiectases with special reference to functional studies]. AB - In 83 patients an unilateral pulmonary resection because of bronchiectasis was performed. The indication was unsuccessful medical treatment. Forty seven patients were re-examined clinically and radiologically and with spirometry and ergooxytensiometry 13.2 years (average) after operation. Good functional results were found in 72.1% of the patients. This justifies pulmonary resection for bronchiectasis even in the era of potent antibiotics. We preferred lobectomy because of its low postoperative complication rate and good functional late results. In bilateral bronchiectasis we operated upon the side with the advanced disease. PMID- 2588692 TI - [Pulmonary hypertension following Rickettsia infection?]. AB - A latent or stable pulmonary hypertension was established in three patients with a Q-Fever-Infection confirmed as occupational disease. According to sparse informations in the literature the development of a pulmonary hypertension in the course of this disease is taken into account. The investigation programme regarding Q-Fever-Infections should be completed by measurement of pulmonary artery pressure. PMID- 2588693 TI - [Comment on the contribution by B. Wiemann and L. Bergmann. "Development of bronchial cancer at the site of siderofibrosis"]. PMID- 2588694 TI - Secretion pattern of retinol-binding protein in blood of goats: effect of vitamin A, provitamin A and their dosing schedule. AB - Studies were conducted on the secretion of retinol-binding protein (RBP) in blood of goats given different treatments of preformed vitamin A, beta-carotene and plant carotenoids. Administration of these sources either in a single massive dose or massive dose split into four equal doses, markedly increased the secretion of RBP in blood. The secretion of RBP in blood occurred at least in two phases, one at early periods and the other at later periods. PMID- 2588695 TI - [The course of vitamin B6 content in growing rats during vitamin B6-free nutrition]. AB - This experiment was designed in two parts. In the first part the vitamin B6 efficiency in response to increasing dietary vitamin B6 intakes was tested in growing rats; in the second part the reaction of rats, originally supplied with the fourfold requirement and then switched on the vitamin-B6-free basal diet was examined. The experimental animals were male Sprague-Dawley rats, of which weight gains, feed intake, and vitamin-B6-concentrations in blood, liver and whole carcass were measured. At the beginning of the trial nine animals were analyzed; 54 additional animals, divided into six groups, were given a vitamin-B6-free semisynthetic diet for three weeks which was supplemented with 0, 1.5, 3, 6, 12, and 24 mg vitamin B6 per kg feed. For the second part the additional 54 animals were given a diet with 24 mg vitamin B6 for three weeks and then switched to the vitamin-B6-free basal diet. Six animals per group were sacrificed after 2, 5, 8, 12, 16, 20, 25, 30, and 35 days of depletion. Efficiency of dietary vitamin B6 decreased from 38% at 1.5 mg vitamin B6 per kg diet to 4% at the 24 mg dietary level. Also, without dietary vitamin B6 the animals gained weight (from 145 to 300 g live weight), the daily feed intake increased from 14 to 19 g and feed efficiency decreased from 2.2 to 4.3 g feed per g gain. Vitamin B6 concentration in tissues reacted differently.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588696 TI - [Comment on the work of Burchard and Tischendorf (Z Ernarungswiss 28:84-91 (1989))]. PMID- 2588697 TI - [Action-oriented versus state-oriented reactions to experimenter-induced failures]. AB - The present study assessed different effects of action-oriented versus state oriented styles of coping with failure on achievement-related performance and cognition. In a learned helplessness experiment, students were exposed to an academic failure situation and were then tested on a series of problem-solving tasks, either immediately after the pretreatment or after a delay of 24 hours. Performance and cognitive concomitants were measured during both experimental periods. Results demonstrated that action orientation was associated with self immunizing cognitions during helplessness training. Action-oriented participants improved their performance level even after repeated failure feedbacks. Moreover, action-oriented students assigned to the delayed test condition responded with increased striving for success and showed performance increments, even in comparison with control subjects. In contrast, state-oriented participants developed symptoms of helplessness and showed impaired performance during failure inductions. In later tests on problem-solving tasks, state-oriented groups responded with increased fear of failure. Independent of immediate or delayed test conditions, they soon lapsed into new performance decrements. PMID- 2588698 TI - [A model of the influence of processing effort and number of changes on subjective time perception]. AB - The paper is concerned with a model for subjective time estimation as determined by processing effort and number of changes. In a previous paper, a proposal was made that should solve a problem of confounded variables in the area of time estimation. An experimental design was developed to allow for the independent manipulation of processing effort and number of changes. It is shown that this proposal is valid only under the assumption that Stevens' law holds with exponent one. Therefore, another way of conceptualizing this problem is advanced in which one asks for the relative impact of processing effort and change on the parameters of Stevens' law. It can be demonstrated that this law yields considerable fit despite interindividual differences. PMID- 2588699 TI - [Speech and conviction as determinants of behavior and perception in interactions: an example of physician-patient relations]. AB - We report on a simulation study with 72 student subjects as well as on an inquiry of 58 patients on the doctor-patient interaction. We were especially interested in inferences that patients draw from general practitioners' behaviors, i.e., their warmth, their kind of talk, and their embarrassment. The simulation study as well as the inquiry reveal patients' inferences that were highly consistent in 9 (out of 16) dependent variables. Patients' inferences on the state of the disease, on the doctor's competence, interest and warmth, on the doctor's kind of talk and sympathy, all consistently depended on the doctor's behaviors. The psychological as well as medical implications of these results are discussed. PMID- 2588700 TI - [Additive hypotheses of the effect of head and eye movement on dark convergence]. AB - Dark vergence depends on the vertical direction of gaze; it decreases with raised gaze and increases with lowered gaze. The vertical direction of gaze can be varied by means or raising or lowering the eyes or by way of tilting the head forward or backward. The effects of both manipulations on dark vergence are different. According to Heuer (1988) the effects of head tilt and eye inclination on dark vergence are almost, but not exactly, additive. In Exp. 1 the hypothesis of additive effects of gaze direction and eye inclination was tested and could not be rejected. The two additive hypotheses (head tilt and eye inclination vs. gaze inclination and eye inclination) result in different predictions for dark vergence with "compensatory" head and eye inclinations, which leave the direction of gaze in space invariant. In Exp. 2 it was shown that predictions from both hypotheses deviated from the observed values of dark vergence. Thus none of the two additive hypotheses provides exact predictions of dark vergence for all possible combinations of head tilt and eye inclination. For practical purposes the approximation might be sufficient. In particular, although mean dark vergence cannot be predicted exactly, individual differences can be predicted quite accurately. PMID- 2588701 TI - [Changes in the EEG frequency spectrum in various phases of mental stress]. AB - To obtain evidence about the relationship between spontaneous EEG activity and mental activity, an experiment was designed and executed with EEG recordings during a concept-learning task. We varied task performance (self-paced vs. machine-paced) and distinguished different stages of information processing during task performance. Using factor analysis calculated on all spectral coefficients, we found two orthogonal variables in the clinical alpha band. Alpha 2 power (10.5-12 Hz) seems to reflect the overall processing demands imposed on the individuals. Furthermore, there are different EEG frequency patterns during perceptual-central- compared with response-related processing as well as during processing of positive vs. negative feedback. The results suggest using (1) conservative procedures in hypothesis testing and (2) procedures to reduce between subject variability (a posteriori defined frequency variables, relative power values, scaling of reaction values) in further studies relating EEG activity to mental activity during task performance. PMID- 2588702 TI - [The effect of control and predictability in learned helplessness]. AB - The present 2 x 2 study deals with the influence of controllability and predictability of an aversive noise stimulus on a subsequent learning task. Eighty-four subjects participated in two experiments. In correspondence with the concept of learned helplessness, controllability was shown to be the dominant factor in the first experiment. In the second experiment, a modified test task was used in which both factors were shown to act in specific ways: The main influence of controllability is upon response measures (latency, omission), whereas unpredictability retardates learning of new predictive connections. The results are discussed in terms of contingency learning. PMID- 2588703 TI - [Effect of the parental home on the oral health status of children]. AB - The oral situation of 507 children and their parents were during the first consultation in a orthodontic department observed and an interview was made with all. The strongest correlation (cc = 0.61) was found between the tooth brushing routine of parents and children. The profession of parents had influence on the oral hygiene, the periodontal condition and the DMF-index of children. The level of oral hygiene of parents had also a favourable effect on the oral hygiene of children. PMID- 2588704 TI - [The attractiveness of various heat insulation substrates and their effect on the reproductive rate of the German cockroach and recommendations for preventing cockroaches]. AB - Attractivity of some heat-isolating materials (glass wool, mineral wool, foam polystyrol, "texdur"-sheets and textile isolating mats) to the German cockroach, Blattella germanica L. and the effects on rate of increase were studied in the laboratory in comparison with folded cardboard as a check. The influence of structure (pressed sheets or loosely quilted materials) and exposition (single, piled or between sheets of plaster) was represented. Loose glass wool, open or between plaster sheets, shows a clearly higher attractivity than the other materials tested. increase of populations on glass wool is almost the same as on folded cardboards. The solid variants were less suitable for the settlement of the cockroaches. General recommendations for the prevention of infestations by cockroaches are given. PMID- 2588705 TI - [Exposure to residues on plant surfaces following the use of plant pesticides in the greenhouse]. AB - Organosphosphorus and carbamate insecticides are quite often used in greenhouses. They represent a group of active principles of toxicological relevance. Initial residues on the surface of cucumber, tomato and ornamental plants, and half-life periods for residue degradation are outlined for carbendazim, dimethoate, fenazox, malathion, methamidophos and pirimiphos-methyl. Residues on plants, concentration in the air, dermal exposition, and inhibition of serum choline esterase activity are shown for methamidophos and aldicarb, respective reentry times being discussed. On harvest and cultivation in greenhouses, dermal exposition as a rule is more relevant than inhalation. PMID- 2588706 TI - [Exposure to residues on plant surfaces following the use of organophosphate insecticides in agricultural apple orchards]. AB - Pesticides based on dimethoate, methamidophos and parathionmethyl are largely used in apple growing centres from the end of May to July. Initial residue concentrations (0.39, 1.4 and 0.4 micrograms.cm-2, respectively) and the degradation of these residues are described together with the relevant half-life periods. They are related to safety margins for residues on leaf surfaces to standardise dermal exposition, respective reentry times being discussed. On the basis of the concentration of active ingredients in the air and of residues on leaf surfaces it is estimated that dermal exposition is predominant on harvest and cultivation in treated apple orchards. PMID- 2588707 TI - [Gas chromatography determination of metalaxyl in plant material]. AB - The control of mycosis on potatoes, tomatoes and cucumbers with metalaxyl demands toxicological evaluation of its residues. It was necessary to elaborate a gaschromatographic method for the determination of the active compound. The plant materials are extracted by homogenization with methanole. The clean up is carried out by precipitate of coextractives, liquid-liquid-partition and column chromatography with aluminia. The quantitative determination is performed on 3% OV 225/Varaport 30, 1.95% OV 210 and 1.5% OV 17 on Chromosorb W HP packed columns and a phenylmethylsilicon fused silica capillary column using a N/P-detector. The minimum detectable quantity is in the range of 0.02 to 0.08 ng. Recoveries from 84 to 92% were obtained after fortification with 0.05 to 1.0 mg/kg. Limits of determination are in the range from 0.05 to 0.5 mg/kg. PMID- 2588708 TI - [Inhalation of carbon disulfide--studies of carbon disulfide uptake in dynamic dose administration lasting 4 hours]. AB - Experiments of CS2 inhalation were accomplished with both constant loads at the ergometer combined with constant concentration of inhalation and discontinuous offered doses combined with various physical loads during 240 minutes. The conditions of the experiment were approximated to the real conditions of exposure at a viscose rayon fibres production. The intake of CS2 increased by 20 percent in case of various conditions. The cause of this finding is a different adaptation during the intake phase in opposition to the breath off phase. The profile of the exposure affected by changed CS2 concentrations and various physical activities is decisive for the intake dosage and thus for the health risk. PMID- 2588709 TI - [Physiologic occupational study of changing technologies in refuse collection]. AB - The strain on drivers and on driver's mates was investigated while emptying 1.1 m(3) containers by means of new dust compressing vehicles, and while removing dustbins of 2201 capacity. A classification was made on the basis of heart rates sampled during the whole shift by portable memories. Extrapolating for the whole shift, the authors measured heart rates of 106.0 min(-1) (drivers) from the 2201 technology. The complementary values from the 1.1 m(3) technology were 107.7 min( 1) (driver's mates) and 105.2 min(-1) (drivers). The men's physical endurance limit would be exceeded when they handled dustbins without break. The investigated tasks are classified to be heavy in both technologies. PMID- 2588710 TI - [Industry branch-specific evaluation of occupational medicine fitness and monitoring examination using a user friendly electronic data processing program for industrial physicians]. AB - Industrial fitness and regular screening examinations as called for by vocational disease regulations in the GDR yield large amounts of data relating to places of work and to those members of the work force whose fitness must be verified prior to employment and at regular intervals thereafter. These data must be available to the work's doctor in the various combinations he needs to ensure the medical well-being of the employees and to act as an adviser on matters of industrial hygiene. Several programs have been developed for implementation on distributed ESER computers to solve this problem. The primary records "Arbeitshygienische Komplexanalyse--Dokumentationsbeleg" (industrial hygiene record) and "Grunduntersuchungsbogen--Datanerfassungsbeleg" (medical data record based on fitness checks) are recorded and checked by desk-top computer and subsequently linked to the wage file record by mainframe for analysis. Examples encountered at a shipyard are used to describe the different programs and some of the ways in which they can be linked. The ability to select any combination of data concerning industrial medical, hygiene and income related matters is a major advantage for the work's doctor. PMID- 2588711 TI - [Incidence of hypertension and borderline hypertension with reference to complex professional stress in above ground and under ground workers in ore mining]. AB - Comprehensive health care for working people requires a deeper insight into the relationship between work load and biological reactions. This is necessary to be able to adequately influence the field of industrial medicine. The incidence of both hypertension and borderline-hypertension in a group of 200 face workers with complex work load as well as 150 pithead metal workers aged between 25 and 45 was measured over a period of 5 years (1981-1986). The hypertension incidence was 0.90% in the group of face workers and 1.46% with the pithead metal workers, while the incidence of borderline-hypertension was 1.30% for the face workers and 2.12% for the pithead metal workers. A statistically significant difference between those people working above ground and those working underground was not apparent. No relationship was found between age, Broca-index, habit of smoking, shift work, the total time away from home and the development of an increase in blood pressure. Both a hypertension incidence totalling 1.14% and an incidence of borderline-hypertension of 1.66% were found in the test group aged between 25 and 45. This roughly corresponded to the nationally statistical level and was in line with the relevant literature. There was no discernable effect with regard to developing hypertension and borderline-hypertension, respectively, as a result of complex work load in the test group. The incidence rates require regular blood pressure tests on normotensive miners and pithead workers, respectively, as a prerequisite for early detection and registering as well as an adequate therapy of both hypertension and borderline-hypertension. PMID- 2588712 TI - [Behavior of blood pressure in 3 shift work of workers with level I WHO hypertension]. AB - Blood pressure tests were carried out on 40 shift workers with a hypertension level of 1 (according to WHO). Every 5 day period these tests were carried out before, during and after work in the early, late and night shifts. No significant change of both the systolic and the diastolic blood pressure could be found, which could result from shift work, before and after each shift irrespective of the blood pressure stabilization (good, satisfactory, unsatisfactory). The group containing satisfactorily as well as unsatisfactorily stabilized workers suffering from hypertension showed a significant decrease of the systolic blood pressure from the early shift through the late till the night shifts, with the diastolic blood pressure remaining constant. There were no apparent differences in the range of average blood pressure values regarding the various forms of treatment (without medication, monotherapy and combined therapy). The systolic blood pressure is significantly lower only in the group with no medication in the early shift after finishing work and it also decreases from the early shift through the late till the night shifts, while within the other therapy groups no change of both the systolic and the diastolic blood pressure was apparent. Thus shift work does not cause any measurable increase in blood pressure within the test group (suffering from hypertension) that would impair their working capacity. There is no increase of health risk with regard to the blood pressure response during shift work particularly during night work provided the blood pressure is within the normal range. PMID- 2588713 TI - [Occupational medicine outpatient management of borderline ophthalmologic fitness at work sites involving traffic]. AB - Employees of transport with specific transport functions underlie a special care by the occupational physician. If vision is impaired, an ophthalmological examination is required, so in unilateral anophthalmia, stronger error of refraction, strabismus, impairment of light perception or other special eye diseases. Dependent on activity and state of health critical parameters are controlled and further conditions are exactly established. Specialized medical care and health control carried out by central health institutions of tractive unit drivers in shift work suffering from glaucoma or wearing contact lenses, of car drivers with ancylosing spondylitis and unilateral anophthalmic wearer of contact lenses, in all operations specific for transport if intraocular lenses as well as for work in areas with malaria risk and cloroquine prophylaxis ensues. PMID- 2588714 TI - [The effect of delayed medical consultation on the results of ergotherapy]. AB - In connection with 567 patients suffering from finger and metacarpale fractures who were treated conservatively the influence of the delaying time on the ergotherapy with its consequences was investigated, but also the influence of the ergotherapy itself. 80.3% of the patients showed a complete rehabilitation after an immediate beginning of ergotherapy. Only 41.0% of the patients remained without residual defects with the beginning of the ergotherapy after a conservative immobilisation therapy. Similar insufficient results were obtained in the group without ergotherapy (only 51.1%). Though after some years the function at late injuries was improved by the help of training in daily life and by means of work remarkable differences between the ergotherapy group and the collective without ergotherapy are recognizable. PMID- 2588715 TI - [Developmental trends in work absenteeism of adolescents]. AB - An extreme negative development in the frequency of adolescent's exemptions from work during 1967-1977 is opposed by a positive development in the following period. Thus, in 1987 adolescents reached the lowest recorded level in respect to illness-caused absentee rates, related to the 1967 level. Therefore, decreases of sickness figures almost exclusively resulted from changes in the younger age groups, especially in adolescents. In the other age groups work absenteeism due to sickness not only remained at the high 1976 level, the year with the highest sickness figure in the GDR, but continuously exceeded it. The results are critically discussed. PMID- 2588717 TI - [Sensitivity of microorganisms of infected root canals to disinfectants]. AB - The bactericidal and growth inhibiting effects of disinfectants on Streptococcus and Candida strains were tested in vitro. Chlorhexidine, when used in tiny concentrations (0.0001-0.0039%) inhibits the growth of Streptococci. With Wofasteril 0.32%) all Streptococci and Candida were killed within a minute. Next to a good bacteria inhibitor (0.001-0.032%), a sufficient bactericidal effect on Streptococci is shown by hydrogen peroxide when used in a 4% concentration and warmed to 45 degrees Centigrade (degrees C). PMID- 2588716 TI - [Disease-related changes in work absenteeism of adolescents from 1967 to 1987]. AB - The negative development of sickness figures up to 1976/77 as well as the subsequent change of this trend in adolescents are analysed with regard to specific diagnoses. Both, the positive trend change and remaining problems are presented. PMID- 2588718 TI - [Occupational disability among teachers and its relation to subjective health status and professional performance]. AB - The aim of this study was to examine the relationship between absenteeism and functional health state, action competence, realization of professional goals and essential needs as well as subjective strain in job and family and type A behaviour pattern. The results of discriminant analyses from a sample of 774 teachers (group 1; no sickness leave days, group 2: sickness leave days greater than 28) are discussed. PMID- 2588719 TI - [Individual physical performance capacity with physiological and biochemical indicators of stress]. AB - 22 health male subjects were exposed by a combination of physical exercises and heat. Strain related physiological and biochemical parameters were measured. Different individual reactions were obtained under controlled conditions. In dependence on the individual performance an increased mobilisation of lactat, free fatty acids and catecholamines were found. The determination of aerob physical performance can be applied for the evaluation of working capacity. PMID- 2588720 TI - [Experiences with a diet-training program in patients with obesity associated diseases including follow-up]. AB - In 158 inpatients (61 m., 97 f.) with obesity-associated diseases were performed a diet-training-programme for about four weeks. We used a PSMF (protein sparing modified fasting) as a 350 kcal diabetic mixed diet, adequate to 4 carbohydrate units (40g carbohydrate, 30g protein, 5g fat) with weekly tea-vegetable-days, additionally wheat brain. The training programme was adapted individually. Reexamination were made by questionnaires and diabetic control cards concerning the body weight. The favourable influence of blood pressure and metabolism was registered. The diet schedule consist natural foodstuffs, fibers, minerals and vitamins. It can be varied, is very effective especially in combination with exercise. The middle term results are rather good more for women than men. Our diet-training-programme can be recommended for outpatients as well as for cures. PMID- 2588721 TI - [Low T3 syndrome and chronic inflammatory rheumatism]. AB - For the clarification of pathogenesis and clinical relevance of decreases of the triiodothyronine (T3) level in patients with chronic inflammatory rheumatism in a group of 63 patients with clinically, paraclinically and roentgenologically diagnosed rheumatoid arthritis (59 times) and with SLE (4 times), respectively, parallel were determined parameters of the thyroid gland function and of the rheumatic activity as well as a subtile drug anamnesis for the medication of antirheumatic drugs was established. In 33 of the 63 patients who were included into the study decreases and low normal values, respectively, for the total T3 (TT3 less than 1.5 nmol/l) were found. In comparison to the remaining 30 patients with normal TT3 a typical constellation of paraclinical parameters of the thyroid gland with distinct reduction of TT3 and free T3 (FT3), low normal total T4 (TT4), slight increase of the reverse T3 (rT3), moderate decrease of the basal and stimulated TSH and an only very small restriction of the binding capacity of the thyroid hormone (TBG) were found. A clinically relevant hypothyroidism is thus to be excluded with certainty. Antirheumatic drugs, in particular steroidal ones (glucocorticoids) may on principle also induce such paraclinical constellations, related to the thyroid gland. In our investigations a therapy with antirheumatic drugs is causally scarcely considered, since both in the group of patients with decrease of T3 and without decrease comparable quantities of antirheumatic drugs including glucocorticoids were administered and the cortisol values in the plasma do not differ. The investigations confirm our already formerly expressed supposition that also in rheumatics a "low-T3-syndrome" is existing as it is otherwise described in consumptive extrathyroidal diseases (NTI).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588722 TI - [The effect of pharmacologic therapy of hyperthyroidism on automatic heart conduction]. AB - Investigations of the heart automatism were carried out in 10 patients with hyperthyreoidism before thiamazol therapy and after restoration of the euthyroid status. A control group was comprised of 34 healthy subjects. In order to determine the electrophysiologic parameters the transoesophageal atrium extrastimulus technique and the over-driving stimulation were applied. Restoration of the euthyroid status was accompanied by a significant prolongation of the atrial refraction, the border interval, the border conductivity and the sinus rhythm recurrence time. In a half of the patients were atrioventricular and intraventricular conductibility disturbances observed. The authors conclude, that in the early period of the euthyroid status restoration after thiamazole therapy there still exists a risk of cardiologic complications. PMID- 2588723 TI - [Porphyria cutanea tarda and lupus erythematosus]. AB - We observed three patients with lupus erythematosus and porphyria cutanea tarda manifesting itself simultaneously or subsequently. The possible coincidence of the two diseases might be the consequence of immunological communities indicated on the assumption of a genetically coined hepatic uroporphyrinogen decarboxylase defect. The treatment of the lupus erythematosus can be performed according to corresponding observations of the course according to general acknowledged principles including the administration of cytostatic drugs, if the chloroquine phosphate therapy which is clearing up the porphyria cutanea tarda is beginning with low dosages. The fluorescence of the fresh kidney bioptate under long-wave UV-light in porphyria cutanea tarda is referred to for the first time. PMID- 2588724 TI - [Recent concepts of the organization and structure of human trabecular bone- results of combined 2- and 3-dimensional analysis]. AB - Every loss of bone mass caused by dysfunction of the endocrine glands and mechanically, respectively, is accompanied by changes of the bone structure. For the pathogenetic mechanisms which in man lead to the abolition of the bone structure in osteoporosis the knowledge of the physiological principles of construction is a basic prerequisite. Hitherto performed studies have shown that with the help of two-dimensional section-cuttings a tridimensional reconstruction is either not possible or can be carried out only by means of serial sections and extensive computer procedures in circumscribed parts. For the analysis of the tridimensional structure of the spongiosa a new method of preparation was developed, which renders possible the simultaneous two-dimensional and tridimensional evaluation of the bone tissue. Seven spinal columns of deceased without disease of the skeleton (donors of organs) between the second and seventh decade of life were evaluated from the dens to the fifth body of the lumbar vertebra. Before the fifth decade of life numerous plate-like structures are existing which in form of intermittent wall carriers lead to a stabilization of the vertebral bodies. With growing age a transformation into rod-shaped trabeculae takes place. This change of structure takes place by large perforations within these plates. Additionally, after the fifth decade of life formations of microcallus occur in a size not known up to now. Apparently an additional process of reparation is existing which shows falsely positive results, when using non-invasive techniques. The results demonstrate the occurrence of perforations with growing age and fundamental changes of the structure of the spongiosa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588726 TI - [Psychological stress conditions at an internal medicine intensive care unit. Analysis of a patient survey]. AB - In an intensive therapy unit of internal medicine for the registration of the contendedness of the patients and the psychic problems of the patients a questioning was performed in the sense of a standardized interview. 55 patients were asked (30 males and 25 females). 89 per cent of the patients stated to have been understandably informed about their disease; 82 per cent said to have been given explanations as to the necessary diagnostic and therapeutic measures. Despite the altogether positive statements of the patients critical viewpoints were also the result which lead to changes. PMID- 2588725 TI - [Idiopathic and diuretic-induced edema]. AB - In female patients with intermitting or permanent inclination to oedemas and intake of diuretics after exclusion of cardiac, renal, venous and lymphogenic causes should be thought of the clinical picture of the idiopathic and diuretic induced oedema, respectively. Pathophysiologically, the two forms underlie an activation of the renin-angiotensin-aldosterone system with subsequent retention of water and common salt. In these cases the intake of diuretics is not indicated and may lead to the chronification of the oedemas. Therefore the physician is confronted with the responsible task to finish the permanent intake of diuretics by adequate explanation of the pathophysiological and pharmacological connections and to care for the frequently neurotic female patients in this difficult time. For a short time a treatment with aldosterone antagonists can be recommended and first therapeutic experiments with the application of ACE-inhibitors were successful. A special diet poor in common salt is not necessary and in the individual case a psychotherapeutic treatment of the female patients should be carried out. PMID- 2588727 TI - [Behavior of serum cholinesterase and acetylcholinesterase activity in acute dimethoate poisoning]. AB - With a patient who in suicidal intention had orally taken a larger quantity of Bi 58 EC (dimethoate) especially the behaviour of the serum cholinesterase activity and the whole blood acetylcholinesterase activity was observed over a period of 38 days and it was compared with the clinical appearance. For the serum cholinesterase activity and the acetylcholinesterase activity a three-phase course that with statistically proven adaption could be described only by a three membered e-function could be shown. Till the 3rd day an extreme decrease of activity of 80-85 per cent occurred. Both cholinesterases provide the same information with regard to the consequences of intoxication. They are only quantitatively different from each other. PMID- 2588728 TI - [Infection and tissue ischemia: what role does the rheologic behavior of blood cells play?]. AB - It is not clear how acute infection is associated with a subsequent ischaemic brain infarction. Infection may, in fact, cause changes in blood fluidity. Abnormalities in blood flow, particularly in white blood cell rheology, are known to be precipitating factors for ischaemic events. Therefore the rheological behaviour of the erythrocytes and the leukocytes were studied 30 days after the onset of acute bacterial infections in 30 patients and in a group of 50 controls (matched for sex, body mass index and cardiovascular risk factors). Our results show a significant impairment in the flow properties of the leukocytes in the patients compared to the controls, and indicate disturbances in leukocyte rheology might be considered an additional risk factor for ischaemic brain infarction when it occurs shortly after febrile infection. PMID- 2588729 TI - [A decrease in height as an expression of disordered bone metabolism in hyperthyroidism]. AB - Disturbances of the bone metabolism are only rarely observed in hyperthyroidism. The description of the case demonstrates clinical signs of osteopathy, connections with the duration of the disease and the possibility to be able to treat on the basis of a fundamental diagnosis. PMID- 2588730 TI - [Primary squamous cell cancer of the thyroid]. AB - A report is given on a 77 year-old-woman with a primary squamous cell carcinoma of the thyroid gland. The tumor had invaded the trachea. Metastases were not found. The patient died of severe bronchopneumonia. PMID- 2588731 TI - [Kidney biopsies in diabetic patients--value of semi-thin layer study]. AB - Kidney biopsies of diabetics were divided into 2 groups: 113 biopsies with conventional paraffin sections (group I) were compared with 154 biopsy specimens with additional examination by semithin sections (group II). In group II glomerular lesions were observed in 81.3%, i.e. about twice as frequently as in group I or compared to the diagnoses made from the paraffin sections in group II, respectively. Most often additionally, diffuse glomerulosclerosis or glomerulonephritis were detected, partly also in combination. PMID- 2588732 TI - [Self-mutilation with a coumarin derivative]. AB - The experiment of a self-injury by permanent intoxication with the coumarin derivative Warfarin is described. Various isolated haemostatic defects as differential-diagnostically demarcated causes for the leading symptom decrease of the value of the thromboplastin time which concern the effect of coumarin are mentioned. It is referred to the coagulation-analytic and chemical-toxic methods of proof of coumarins. PMID- 2588733 TI - [The behavior of leukocyte rheology in induced ischemia in peripheral arterial occlusive disease]. AB - We studied the quantitative and qualitative behaviour of white blood cells (WBCs) at rest and after standard treadmill exercise in 20 male stage II peripheral vascular disease (PVD) patients, compared to 20 healthy matched controls. The aim of this study was to define the role of WBCs in PVD. The results confirm the WBC count was significantly increased in PVD patients. Surprisingly, however, the only rheological WBC variable which showed a significant variation during the ischaemic pain caused by treadmill exercise was the filterability of mononuclear leukocytes. This would seem to identify disturbances in mononuclear filter ability, associated with ischaemic pain resulting from claudication, as a functional sign of PVD. PMID- 2588734 TI - [The value of computerized tomography for preoperative staging of stomach cancer]. AB - The validity of computed tomography (CT) for the preoperative staging (TNM) of gastric carcinoma was studied in 74 patients, first in a prospective study, then under routine clinical conditions. Comparing CT-staging to intraoperative findings in the study patients showed correct assessment of the T-category in 70%, the N-category in 36%, and of both T and N in 26%. Validity was also low with 27% for both T- and N-staging when the CT was set against pathological anatomical findings. The results in clinical routine were even more disappointing. The examination is of little value for deciding on operative indication and planning. Computed tomography therefore should not be part of a preoperative routine diagnostic assessment in gastric carcinoma. PMID- 2588736 TI - [Screening for colorectal neoplasms: comparison of Hemdetect and Haemoccult]. AB - Comparison of a 3-hole-version (HEMDETECT) with the standard 2-hole HAEMOCCULT guajac-test for fecal occult blood revealed a 4.2% positivity rate for HEMDETECT versa 3.4% for HAEMOCCULT. The higher sensitivity of HEMDETECT was accompanied with an increased detection rate of colorectal neoplasias. PMID- 2588735 TI - [Disorders of intestinal absorption in patients treated with cytostatic chemotherapy]. AB - We have investigated the acute and chronic side effects of cancer chemotherapy on the intestinal absorption of adult patients with neoplastic diseases. D-xylose absorption was reduced by 35% in 34 of 50 patients within 48 hours after one course (p less than 0.001), while the vitamin B12 absorption was diminished by 41% in 27 of 38 patients (p less than 0.001). The serum digoxin level fell in 7 of 8 patients by 43% at the first day (p less than 0.01) and normalized after one week. Electron microscopy of the jejunal biopsy specimens revealed damages of the microvilli and defects in the glycocalix. Chronic effects, which were measured after several courses and a pause of four weeks, showed a diminished D-xylose absorption of 36% in 16 of 19 cases (p less than 0.01). Vitamin B12 absorption was reduced by 37% in 11 of 13 patients (p less than 0.01). Microscopical investigations of the jejunum revealed a shortening of the villi and a destruction of microvilli. Acute and chronic malabsorption after cancer chemotherapy should be considered in patients, who are treated with enteral medication and nutrition. PMID- 2588737 TI - [Smoking and inflammatory bowel diseases]. AB - In a case-control study 142 patients with Crohn's disease, 189 patients with ulcerative colitis and matched community controls were questioned about their smoking habits. When assessed by smoking habits before the onset of disease, patients with Crohn's disease were four times as likely to have been smokers than their matched controls. In contrast, patients with ulcerative colitis were ten times less likely to have been smokers compared with their matched controls. There was no confounding by social class or alcohol intake differences. The contrasting nature of these associations suggests that there might be an aetiological role for smoking in inflammatory bowel disease. PMID- 2588738 TI - The nicotinic acid test in the evaluation of unconjugated hyperbilirubinemia. AB - In 42 young adults with Gilbert's syndrome and in 9 patients with inactive, well compensated liver cirrhosis the peroral nicotinic acid test was performed. Of the 13 parameters tested, the groups differed significantly in the sum of total and unconjugated serum bilirubin concentrations, respectively, during the test; in the difference between the maximal and initial concentrations of total and unconjugated bilirubin; in the retention of total bilirubin at the third, fourth and fifth hour of the test; and in the size of the area under the curve of unconjugated bilirubin increase. However, due to considerable overlap, no single parameter could reliably differentiate among all persons with Gilbert's syndrome and cirrhotics. The nicotinic acid test is neither necessary for the diagnosis of Gilbert's syndrome nor can it reliably differentiate between this condition and severe organic liver disease. Yet, it does supply valuable information about the readiness of the organism to develop or enhance hyperbilirubinemia following a defined stimulus. PMID- 2588740 TI - [Quantitative liver function tests--a new trend or sensible measure?]. PMID- 2588739 TI - [Atrophy of the corpus mucosa of the stomach simulating polyposis]. AB - We report on five cases of mucosal atrophy of the gastric body, under the aspect of a polyposis: These polyps showed intact mucosa with abundant fundic glands and were situated in the diffuse atrophic mucosa of the gastric body. Four of these cases were manifestations of type A gastritis, in one case the lesion surrounded a peptic ulcer. Laboratory findings of serologically analysed cases with type A gastritis showed elevated parietal cell antibodies in all cases, two of three cases showed a high level of gastrin, the values for vitamin B12 showed different levels; no patients revealed antibodies against the intrinsic factor, and no patient had pernicious anemia. The family history revealed three cases with cancer of the stomach on one side of the parents. It is important to biopsy polyps and the flat mucosa separately in order to verify this form of atrophy of the gastric mucosa and to also exclude small polypous tumors of the mucosa. Observation of the number of polyps allows a control of the extent of the atrophy of the mucosa. PMID- 2588741 TI - [44th meeting of the German Society for Digestive and Metabolic Diseases with the Section of Gastroenterological Endoscopy. Mainz, 27-30 September 1989. Abstracts]. PMID- 2588742 TI - Morbidity in a microsurgical rat training model. AB - In a prospective study with 24 growing Wistar rats, with a mean body weight of 300 gram, microsurgery was trained. Patency as well as morbidity of the animals was assessed. There were 110 vascular anastomoses, constructed with various techniques. Of these, 104 were rendered for evaluation. The caliber of the vessels varied from 0.4 to 2.0 mm. On an average, the rats were operated two times, during which operations at least four anastomoses were created. Patency was related to caliber and flow rate of the vessel and varied between 50 and 100%. Mortality and weight increase, used to reflect morbidity were evaluated. Six animals died during or shortly after operation, three of them because of anaesthesia alone. Mean postoperative daily weight increase was 1 gram approximately. In the control group the weight increase was tripled. The rats needed two weeks after operation rats to regain their original weight. Analysis of results demonstrated highly significant difference between operated and non operated rats. The study suggests, that morbidity of rats submitted to microsurgery will be reduced, if two weeks of recovery before other experiments are awaited. This may provide a standard for future experiments. PMID- 2588743 TI - [Methods for the analysis of the psychosocial behavior of the quality of life index in rats with different reconstructions after gastrectomy]. AB - Standardized behaviour monitoring in rats is a well-suited method for the evaluation of behavioral und nutritional effects following reconstruction surgery. Using an experimental design possible side effects resulting from the original disease can be excluded, which is an important advantage compared to clinical studies. Behavioural effects can be related to changes in biological functions following surgery. After gastrectomy 10 rats were reconstructed by Roux Y-technique and 10 other animals by oesophagoduodenal interposition. In an open field-behaviour-test they were compared with 10 sham operated and 10 untreated controls. Differential effects can be shown by special behavioural indices. PMID- 2588744 TI - Pancreatic exocrine secretion--a measure of the functional capacity of the pancreatic energy metabolism. AB - In studies on the pathogenesis of ischemic cell injury and of other pancreatic diseases the knowledge of the actual pancreatic energy state is an important factor. Therefore, it would be advantageous to have a simple and inexpensive method to determine this parameter and its alterations in the pancreas. At uniform hormonal stimulation, the extent of exocrine pancreatic secretion showed a clear dependence on energy supply in this organ. The degree of pancreatic juice edema formed after bolus injection of cholecystokinin and secretin at ductal occlusion was found to be the most sensitive and reproducible measure of the functional capacity of the pancreatic energy metabolism. While this parameter can be applied to experimental studies, only, the juice volume secreted could be determined under clinical conditions, too. Both parameters of pancreatic secretion were clearly decreased after preceding short-term ischemia and recovered after an adequate interval of reperfusion. PMID- 2588745 TI - [The effect of donor conditioning with cyclosporin on the survival time of allogenic heart transplants in the rat]. AB - The aim of the study was to investigate the influence of a pretreatment of the heart donor with cyclosporin (CsA) at 25 or 50 mg kg BW on day -1 on survival time of rat heart allografts in a donor-recipient combination that was different at their major histocompatibility complex (MHC). No further immunosuppression was used. The survival of CsA-pretreated heart transplants was significantly prolonged in allogeneic recipients compared with untreated controls and 3 out of 10 grafts (25 mg kg) and 4 out of 9 grafts (50 mg kg) survived permanently. These preliminary experimental findings are new, but further investigations are necessary to increase the efficacy of this pretreatment protocol. PMID- 2588746 TI - [Extending the survival time of allogenic heart and kidney transplants in the rat by a combination of PUVA transplant conditioning and cyclosporin treatment of the recipient]. AB - Dose-response studies of cyclosporin (CsA) established that a dose of 2 mg kg body weight on day 0 was of therapeutic suboptimal value in rat kidney allotransplantation. When PUVA-treated heart and kidney allografts were transplanted into temporary CsA immunosuppressed recipients the graft survival rates were further improved as compared with PUVA alone. Forty vs. 18% (heart) and 70 vs. 40% (kidney) of the PUVA + CsA vs. PUVA treated allografts survived permanently. Therefore a synergistic effect of PUVA pretreatment and low-dose CsA therapy on rat heart and renal allograft survival was demonstrated. PMID- 2588747 TI - [Immunosuppressive therapy with low cyclosporin A doses in rats]. AB - An optimum blood level of cyclosporine-A (Cs-A) after allotransplantation in rats is very important for the survival of the transplanted organ. An auxiliary allotransplantation of the heart into the abdominal cavity were carried out in 10 rats. A Cs-A blood level of 200 to 300 ng ml was obtained by administration in the animal food in a dosage of 7 mg kg body weight day. A rejection of the graft was prevented in this way without any symptom of toxicity during 90 days. The results of the experiments were well reproducible. The obtained Cs-A blood level is relatively stationary, frequent laboratory tests are not necessary. PMID- 2588748 TI - The radiological examination of the pancreas harvested for transplantation. AB - The radiological examination of the pancreatic arterial blood supply was performed to show the presence of the arterial variability. 40 arteriograms of pancreatic vessels were made. The research confirmed the subsistence of the arterial variability concerning the dorsal pancreatic artery in particular. The importance of the previous arteriography in donor, before harvesting the pancreatic graft, was unterlined. PMID- 2588750 TI - [Light microscopic studies of the cartilage in funnel chest. A new view of the pathogenesis]. AB - In patients with a funnel chest, light-microscopic studies of their rib cartilage showed vessels in all slices of the cartilage. In all analysed stages of life there is a constant number of vessels per unit area; even in not deformed parts of the cartilage. Furthermore, the number of the chondrocytes strongly increases within the single chondrons with rising age in an extraordinary way. PMID- 2588749 TI - [The use of tantalum wire as a suture material]. AB - The qualification of tantalum wire as suture material was tested by means of physical and histological investigations. Starting-point were the physiochemical and biological attributes and its hitherto existing employment in the medicine. Indication and recommendations for handling the material were found out. PMID- 2588752 TI - [Multiple basaloid follicular hamartomas in 2 members of a family with Gorlin Goltz syndrome]. AB - We report on a 20-year-old man and a 14-year-old girl showing multiple basaloid follicular hemartomas on face and upper back. Both patients were members of a family with Gorlin-Goltz syndrome. PMID- 2588751 TI - [Treatment of alopecia areata of the eyebrow with diphenylcyclopropenone and its possible risks]. AB - The treatment of alopecia areata (AA) with diphencyprone is well established and acknowledged. Up to now, diphencyprone has only been applied in case of AA of the capillitium. Thus, for the first time, we used this substance in the treatment of AA of the eyebrows. In consideration of the possible risks, we discuss the necessary precautions regarding the patient, as well as possible side effects. PMID- 2588753 TI - [The significance of ventricular tachycardia morphology for prognosis and follow up]. AB - To assess the prognostic value of ventricular tachycardia (VT) morphology we studied data from 56 patients (pts) with old myocardial infarctions and documented sustained monomorphic VT. There were 22/56 pts (39%) with a left bundle branch block (LBBB) pattern of the spontaneous VT and 34/56 pts (61%) with a right bundle branch block (RBBB) VT. During a mean follow-up of 34 +/- 11 months, 12 pts died from cardiac causes, four of them suddenly. Total mortality was higher in pts with RBBB-VT (9/34, 26%) than in those with LBBB-VT (3/22, 14%) (p = 0.21), despite a significantly shorter VT cycle length in pts with LBBB-VT (306 +/- 56 ms) than in those with RBBB-VT (344 +/- 76 ms) (p less than 0.05). All pts who died suddenly had a RBBB-VT. During programmed stimulation, VT with the same morphology as the spontaneous VT was induced more frequently in pts with LBBB-VT (off drugs: 7/14, 50%; on drugs: 10/16, 63%) than in pts with RBBB-VT (off drugs: 7/20, 35%, on drugs: 8/28, 29%) (p = ns). In contrast, VT with different or multiple morphologies were induced more frequently in pts with RBBB VT (off drugs: 13/20, 65%; on drugs: 20/28, 71%) than in pts with LBBB-VT (off drugs: 7/14, 50%; on drugs: 6/16, 38%) (p less than 0.05). Our data show that there is a higher risk of cardiac and sudden death in pts with RBBB-VT than in those with LBBB-VT after myocardial infarction, despite a shorter cycle length of the spontaneous VT in patients with LBBB-VT. PMID- 2588754 TI - [Behavior of ventricular late potentials following catheter ablation of ventricular tachycardia]. AB - In 10 patients non-invasively recorded signal-averaged electrocardiograms were obtained before and after direct-current ablation of ventricular tachycardia (right ventricular origin n = 5; left ventricular origin n = 5). The algorithms proposed by Simson and Karbenn et al. were used (modified Frank leads, high-pass filter cut-off frequency 25 Hz). No differences were observed between the mean values of the duration of the QRS-complex, the mean voltage during the last 40 ms of the QRS-complex, the duration of the late potentials and the number of patients having late potentials before and after ablation, respectively. The success of ablation could not be predicted by the signal-averaged ECG. There was no difference between the averaging parameters of those patients without recurrences of ventricular tachycardia during the follow-up period and those with (n = 3). Thus, the signal-averaged ECG did not prove helpful in predicting a successful outcome of direct-current catheter ablation of ventricular tachycardia. PMID- 2588755 TI - [Use of a noninvasive parameter of early diastolic ventricle function for the detection of graft rejection following heart transplantation]. AB - Since changes in left ventricular early diastolic time intervals can be expected as one of the first detectable functional alterations indicating acute rejection in cardiac transplant patients, time-constant Te, a parameter derived from digitized M-mode echocardiogram, was proved as a marker of acute rejection. Echo results of 30 transplant patients (5-63 yrs) were correlated with myocardial biopsy results (48 rejection negative, 16 rejection positive) of the same day. In transplant patients the M-mode echo parameter Te is prolonged even in phases without rejection (79.0 +/- 12.5 ms vs 64.0 +/- 7.9 ms of healthy controls; p less than 0.0001). Te of transplant patients during rejection were significantly longer than Te of patients without rejection (97.8 +/- 17.9 ms vs 79.0 +/- 12.5 ms; p less than 0.0001). Individual courses demonstrate that rejection is associated with further prolongation of Te and that Te returns to individual basic value in response to treatment. So, Te may prove as a useful noninvasive marker of acute cardiac rejection. PMID- 2588756 TI - [The accuracy of Doppler echocardiography determination of shunt volume in children with isolated atrial septal defect and left-right shunt]. AB - The accuracy of shunt calculations derived from Doppler echocardiography was assessed in 15 children (5-15 years, mean 8.5 yrs.) with secundum-type atrial septal defect and left-to-right (L-R) shunt. Qp/Qs was calculated by measuring stroke volumes over the aorta and pulmonary artery prior to and 4-15 days after corrective surgery. The measuring error of the Doppler method was defined as deviation of the postoperative shunt value from zero. A residual shunt was excluded by careful intraoperative testing and physical examination. Intraoperative inspection revealed normal pulmonary venous drainage. L-R-shunt, as calculated by Doppler echo, significantly decreased after surgery (p less than 0.001). Although all septal defects were closed, calculations by Doppler echo resulted in a median residual shunt of 16% (0-50.7%). IN 2/15 children a L-R shunt of more than 40% was derived by echo recordings. The size of the measuring error increased in children with great preoperative shunts. There was a significant correlation between the ratio of pulmonary to aortic cross-sectional area and the measuring error (p less than 0.03, r = 0.59). Poor estimation of cross-sectional areas in dilated pulmonary arteries was the most important limiting factor in shunt calculation. Doppler echocardiography provides a valuable noninvasive method for shunt calculation. Similarly to Fick's principle, in some patients the measuring error may be considerable and become relevant for clinical decisions. Thus Doppler-derived shunt calculations must be complemented by additional information of two-dimensional echo and physical examination. PMID- 2588758 TI - [Nitrate therapy. Status in 1989]. PMID- 2588757 TI - [Coronary artery spasm as a rare cause of sudden heart arrest]. AB - After successful resuscitation only few patients present without any findings indicative of the causes of their cardiac arrest. We report on a 39-year-old woman who had normal clinical, electrocardiographic, and angiographic findings after she was successfully resuscitated. In contrast to other patients without apparent organic heart disease she had three cardiac arrests within 10 months; each episode was preceded by an ascending epigastric pain. During an attack with epigastric pain a long-term ECG recording documented an increasing ST-segment elevation followed by rapid, non-sustained ventricular tachycardia. Intravenous ergonovine induced a spasm of the right coronary artery with a subtotal vessel occlusion and an ST-elevation in lead III. After medication with a calcium antagonist no coronary vasospasm was demonstrated. For 11 months the patient has been without any complaints. PMID- 2588759 TI - Correlation between isosorbide dinitrate plasma levels and coronary vasodilation after chewing capsules. AB - In 10 patients with coronary artery disease coronary angiograms were performed in identical projections before and 5, 10 and 15 min after sublingual administration of two chewing capsules with 5 mg of isosorbide dinitrate (ISDN) each. Simultaneously, blood samples were taken for gas-chromatographical determination of nitrate plasma levels. The average ISDN plasma levels amounted to 138 +/- 73 ng/ml, 102 +/- 76 ng/ml and 62 +/- 34 ng/ml in the fifth, tenth and fifteenth min, resp. In the fifteenth min significant isosorbide mononitrate plasma levels (greater than 70 ng/ml) were found only in three patients. Mean diameters of angiographically normal coronary segments were measured with the automatic edge detection system CAAS; they increased by an average of 20 +/- 10%, 26 +/- 11%, and 27 +/- 13% (p less than 0.001) in the fifth, tenth and fifteenth min, resp. Due to hysteresis of the coronary dilation in relation to ISDN plasma levels no significant correlation was found between these parameters. The minimal diameters of seven of 10 coronary stenoses analyzed in seven patients reacted with a maximal increase of 23%-98%. Thus, ISDN chewing capsules may be preferable for rapid and prolonged relief of anginal attacks as well as for potent dilation of epicardial coronary arteries as desired during angiography. PMID- 2588760 TI - [Control of the effectiveness of nitrate therapy with long-term ECG based on spontaneous ST segment changes]. AB - In a population of 40 patients with coronary artery disease the overall incidence of spontaneous ischemic episodes during 24-h Holter monitoring could be significantly reduced with ISDN 120 mg ret. and ISDN 120 mg plus Diltiazem 120 mg ret. However, the intraindividual day-to-day variability of ischemic episodes on three consecutive days of Holter monitoring is taken into consideration, an intraindividual reduction of ischemic episodes of at least 97% is required to separate a true therapeutic effect from the considerable spontaneous variability. PMID- 2588761 TI - [Combination therapy with isosorbide dinitrate and verapamil in patients with coronary heart disease and hypertension: effect on blood pressure, ischemia and left ventricular function]. AB - In the treatment of myocardial ischemia in hypertensive patients, nitrates as the basic compound have to be combined with another substance in order to achieve a maximum effect and a 24-h-protection. As these patients often show an impaired left ventricular function because of arterial hypertension or previous myocardial infarction, a further deterioration of the left ventricular ejection fraction (EF) has to be avoided. We therefore investigated in a pilot study. EF, blood pressure, and ST-segment depression under isosorbide dinitrate 120 mg s.r. alone, and in combination with verapamil 120 mg s.r. in 14 male patients with angiographically proven coronary artery disease and arterial hypertension. EF at rest ranged from 29% to 76%. Radionuclide ventriculography was performed at rest and simultaneously with the ECG during exercise before medication, 2 h after ISDN and 4 h after the additional intake of verapamil. The systolic blood pressure at rest fell from 159 +/- 14 to 132 +/- 10 (p less than 0.001) after 2 h and to 132 +/- 16 mmHg after 6 h (p less than 0.01). During exercise there was a decrease from 196 +/- 21 to 174 +/- 21 (p less than 0.01) and to 178 +/- 22 mmHg (p less than 0.001), respectively. The ST-segment depression was reduced from 2.2 +/- 1.1 to 0.8 +/- 0.6 (p less than 0.01) and to 0.9 +/- 0.5 mm (p less than 0.001). EF at rest improved from 53 +/- 14% to 57 +/- 14% after ISDN alone and to 58 +/- 15% after ISDN + verapamil (p less than 0.01), and during exercise from 57 +/- 20% to 62 +/- 19% (p less than 0.05) and to 61 +/- 17% (n.s.). Even in the subgroup of patients with impaired LV-EF (8 at rest and 7 pts during exercise) there was a significant improvement (p less than 0.05) as well after ISDN alone, as there was with combination therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588763 TI - [Gerontopsychiatry]. PMID- 2588762 TI - Clinical chronopharmacology of oral nitrates. AB - The clinical-chronopharmacological investigations with oral nitrates (ISDN, IS-5 MN) demonstrate that the drugs' pharmacokinetics and/or hemodynamic effects are circadian phase-dependent. For both an immediate-release and a sustained-release preparation of IS-5-MN peak drug concentrations coincided with peak drug effects after morning but not after evening drug application. Results indicate a circadian phase-dependency in the dose-response relationship of oral nitrates. PMID- 2588764 TI - [Normal pressure hydrocephalus in geriatric patients--a treatable form of dementia]. AB - Six geriatric patients are presented who were treated because of normal pressure hydrocephalus. A tentative diagnosis was made if dementia, gait disturbance, and incontinence together with a typical CAT-scan were present. In these cases an operation was carried out. After ventriculo-peritoneal shunting clinical improvements were seen in four patients. Postoperative complications were hygromas in three patients and a shunt-dislocation in another patient. A chronic subdural bleeding was recorded also in one of these patients with only a temporary success in this case. Two patients showed no clinical improvement at any time. However, in these cases additional neurologic symptoms together with typical CAT-scan changes were present. Before making a decision for an operation vascular processes and Alzheimer's disease should be ruled out. PMID- 2588765 TI - Delusional depression in the elderly: a community study. AB - The prevalence of delusional depression, its symptoms and signs, and social and health status of delusional depressives were studied in a Finnish population aged 60 years or over. The prevalence was six per 1,000 men, 12 per 1,000 women, and 10 per 1,000 for both sexes. The overall symptomatology of delusional depressives was more severe than that of nondelusional major depressives or of all nondelusional depressives. The mean age at the onset of depression and the mean duration of depression did not differ between delusional and nondelusional major depressives. Although delusional depressed elderly did not significantly differ statistically from nondelusional major depressives in social status, somatic health status, functional capacity, or occurrence of social or health stress factors; they tended to have a better somatic health status and they tended to be more lonely. The small number of delusional depressives does not give us the opportunity to draw straightforward conclusions about whether elderly delusional depressives are a subcategory differing from other elderly major depressives. PMID- 2588767 TI - [Vitality, functional age and biological functional age. A contribution to the problem of the time concept in theoretical gerontology]. AB - With the aid of a vitality concept it is possible to find a relationship between chronological time and functional time of an organism. This relationship allows to calculate the functional time-shift between two organisms which have different parameters of aging. PMID- 2588766 TI - [The relation between suicide and psychiatric disease in advanced age]. AB - This report addresses the relation of suicide to mental illness in the elderly. Our investigation of this relation proceeds from the following two points of view: First we asked whether the fact that the elderly are most at risk from suicide is enhanced by their increased psychiatric morbidity. Secondly, sought to determine to what extent suicides of older mentally ill persons are definitely a result of their mental illness. The sample includes 310 suicides of psychiatric inpatients. These were investigated in the course of a multicenter study of six psychiatric State Hospitals in southern West Germany. The method of analysis involved the motives of the suicidal acts. Results demonstrate that age is an autonomous risk factor and not affected by psychiatric morbidity. Psychiatric morbidity of older persons is not sufficient to explain the suicidal act. Moreover, we found that if mental illness played a part, motives reflecting aspects of chronicity predominated motives reflecting psychopathology (i.e., being presecuted, losing one's mind) of the suicidal patients. Results are discussed with special reference to prevention and management of suicide risk factors in the elderly. PMID- 2588768 TI - [Contact and emotional relations between married children and their parents]. AB - In a two-stage project we investigated the dimensions of the emotional relationship between married children and their parents, as well as the connection with different areas of interaction. Both generations classify their relationship as positive and close, basically formed by trust and understanding. Dependencies do not impair the core of the relationship. Frequent contact indicates a good relationship, if not solely motivated by help. The frequency of help rendered gives only little evidence about the quality of the relation; also barely significant is absence of divergent viewpoints or the exchange of caresses. More significantly, open communication, requests for help, positive reaction to caresses, and voluntary contact point to a positive relation. PMID- 2588769 TI - [Gerontology in Brazil]. PMID- 2588770 TI - [Health and morbidity of children in the North]. AB - The author's many-years' experience and the literature data on research into the health of children and adults during adaptation in the Arctic are generalised. Significant changes are demonstrated in seasonal and circadian biological rhythms, in hormone levels, immunological tests and functional parameters of oxygen transport and consumption, and permanent exhaustion of these and other functional systems. At the same time, it has been proved that in the recent twenty years, the physical and mental development of children and adolescents has been quite satisfactory and their morbidity is not higher than that of Central Siberia, while childhood mortality level is noticeably lower. A conclusion has been drawn on the possibility of reducing the adaptational tension and functional reserve exhaustion, and of children's health improvement in the Arctic by means of social protection (housing, nutrition, etc.) and rational training (body hardening, physical exercises, etc.). PMID- 2588771 TI - [Health problems of thermoregulation in humans in the Far North]. AB - The experimental and natural studies have revealed the role of the low-humidity Far-North environment in forming a specific heat-exchange pattern and corresponding functional and morphological changes in the organism, and have confirmed the biological and hygienic importance of the low-humidity environment. PMID- 2588773 TI - [Health problems in the development of new cities in the Baikal-Amur Railroads region]. AB - The presented findings of research on the sanitary and hygienic status of the BAM regional cities and towns and assessment of their (and their analogues) developmental perspectives have revealed the interregional difference in climate and nature dictating a differential approach to planning urbanisation of this region's specific areas. Based on the analysis of urban planning and construction and on special observations, measures aimed at environmental protection and population morbidity control have been elaborated and implemented. PMID- 2588772 TI - [Interactions between the body and harmful substances in cold conditions]. AB - The complex of physiological reactions caused by cooling is shown to change nonspecifically the organism's toxicokinetics and sensitivity to poisons resulting in considerably increased intake of inhaled harmful substances and their more rapid, though less significantly, elimination. A redistribution of heavy metals in the organism is possible, for example, prolonged cobalt retention in the adrenals. Cooling slows down association and dissociation rates of carboxyhaemoglobin in acute carbonic oxide poisoning. An increase in the acute toxicity of poisons is characteristic for the initial stages of cooling, although in pronounced hypothermia the acute effect of poisons is progressively reduced. PMID- 2588774 TI - [Mechanism of the development of chronicity of pathologic processes in the North]. AB - Based on the analysis of morbidity and population's immunity status in the North, a conclusion has been drawn that changes in the immunological reactivity of the organism due to autosensitization form the basis for chronization of pathological processes in the Far North. The discussion of the problem is supported by the correlation of the findings with the material characterizing the infections developed in sensitization of the organism with other antigens (as exemplified by opisthorchiasis invasion). A hypothesis is made that chronic population stresses and mass-scale allergization of the population are causes of the recent global trend toward formation of chronic pathology. PMID- 2588775 TI - [Development of scientific research in the area of protection of human health and environment]. PMID- 2588776 TI - [Work conditions and health status of workers in coal mining open pits of the Kansk-Achinsk fuel-energy complex and the Southern Yakutsk coal complex]. AB - A hygienic assessment of the working conditions at the open-cast mines of KATEK and YuYaUK showed that the conditions were better at KATEK than at the Neryungrin mine, due to milder climate, non-transport system of stripping, wheel-type trenching, and railway transport in the mining areas. No cases of occupational disease were registered. The working conditions and the character of work may influence the general morbidity, in particular the development of cardiovascular disease. The efficacy of health promotion actions is analysed and recommendations on further improvement of the working conditions are presented. PMID- 2588777 TI - [Influence of industrial-occupational, climatic and geographic factors on the health of miners in the Northeastern part of the country]. AB - Miners working in the North are exposed to more pronounced effects of unfavourable occupational factors (hand drillers, bulldozer operators, etc.) and are found to have higher morbidity rates. With their longer stay in the North, the incidence of gastrointestinal disorders increases. Among the migrants from the regions with contrasting climatic conditions. (Caucasus, Central Asia), the morbidity is higher than among those from other regions of this country. PMID- 2588778 TI - [Nutritional status of several population groups in the Far East and Extreme North]. AB - Studies of the actual nutrition and wide spectrum of biochemical, haematological, and anthropometric indices in the representatives of the native population of Kamchatka and Chukotka showed that along with the significant changes in nutritional patterns due to the added products, local sources of feeding (fish, sea mammals, deer meat) greatly contribute to fulfilling the physiological requirements and exert a specific effect on metabolic processes. This is mostly associated with the features of lipid metabolism as a result of marine fat intake. Recommendations on the rational nutrition organization in these regions are discussed. PMID- 2588779 TI - [Health and ecological problems connected with development of the North]. AB - Nature and climate determine the conditions of life and work in the North, a complex ecological and sanitary situation in the newly-explored Northern regions of the country. To maintain and improve health of the population of these regions is a problem of utmost complexity and importance. A number of research institutes of the USSR AMS and Ministry of Health deal with these problems, within the framework of the programme "Health of Man in Siberia". A new important trend in the research into the hygienic problems is to study the populational health status and morbidity patterns based on the systemic approach taking into account the effects of all environmental factors and, in particular, the working conditions, nutrition, habitat, social events, and mode of life. PMID- 2588780 TI - [Lessons of cholera pandemic VII]. AB - Basic epidemiological regularities of El-Tor Cholera during pandemic VII are described with differentiation of the four periods of its global spread and evaluation of the efficacy of therapeutic and preventive measures. The findings of studies into the ecology of the causative organism in the surface water basins testify to the possibility of its long-lasting existence in the saprophytic phase, which requires differentiation of the anti-cholera actions. The necessity of improvement of the global epidemiological control is substantiated. PMID- 2588781 TI - [Human ecology and the problem of health]. AB - The influence of scientific and technical progress on the health of population is analysed. It is noted, that modern medicine deals with negative consequences of scientific and technical progress mainly, with the people, who weren't able to adapt to the conditions of environment. A necessity of improvement and development of approaches to estimation of the levels of health is revealed. The two important problems of human ecology are described: the monitoring of environment and the influence of the environment on the health and socio-labour people's potential. The examples of bio-ecological monitoring of environment on the basis of population's health structure in different territorial and industrial complexes are presented. The health of human population is examined as a socio-economic subjects. PMID- 2588782 TI - [Cellular glucocorticoid reception in man and differences in type of reaction to stress]. AB - Three groups of individuals were investigated, which differed in constitution and reaction to stress. Group I comprised randomly selected individuals. Groups II and III were formed of highly qualified athletes, weight lifters and marathoners who matched those from Group I. Studies of the hormonal profile revealed significant differences in the baseline cortisol levels between Groups II and III. Evaluation of parameters of glucocorticoid reception by cultured individuals' fibroblasts also showed significant differences between Groups II and III. Employment of complex quantitative characteristics of potential cell sensitivity to the effect of physiological glucocorticoid concentrations, and of the resting biological effect of this hormone, characterising the efficacy of glucocorticoid reception in postreceptor and glucocorticoid-dependent processes in somatic cells, allowed for adequate qualitative evaluation of glucocorticoid dependent reactions to stress on the cellular level which is indicative of the stress reaction type of the organism as a whole. Thus, genetically determined variability of cellular parameters was first revealed, the parameters being directly related to the ontogenetic formation of the stress reaction type. It is biologically understandable that this variability correlates with human resistance to long-term psychosomatic stress. PMID- 2588783 TI - [Economical bases of the organization of scientific research in the field of medicine]. PMID- 2588784 TI - [Carbohydrate metabolism in patients with chronic pyoderma and its dynamics during therapy using sugar-decreasing preparations]. AB - Carbohydrate metabolism has been examined in 301 patients with chronic pyoderma over the course of combined therapy including sugar-reducing drugs; biochemical methods (measurement of the blood sugar on an empty stomach, Staub-Traugott double carbohydrate load test, measurement of the blood serum seromucoid) and radioimmunoassay of the blood serum immunoreactive insulin have been employed. Diabetes mellitus has been first diagnosed in 2.9% of patients, latent diabetes in 18.8%, and in 4.7% of the examinees the parameters indicate the risk of this condition development. Combined therapy improves the examined parameters, providing good immediate and late results. These data favor the use of sugar reducing agents in multiple-modality therapy of patients with chronic pyoderma. PMID- 2588785 TI - [Ultrastructural changes in the epidermis in ichthyosis vulgaris]. AB - Electron-microscopic examinations of the epidermis in 11 patients suffering from xeroderma with autosomal dominant and X-recessive inheritance have revealed changes in the basal membrane, scarce pinocytotic vesicles near the basal membrane, inter- and intracellular edemas in the epidermis, a decrease of the desmosomal contacts and an increased number of microvilli on the epidermocytes of the basal and prickle-cell layers, condensation of the nucleoplasm, reduced counts of organelles and condensation of the epidermocyte tonofilaments, hyperkeratosis, and an elevated count of the desmosomes in the horny layer in both forms of ichthyosis. Autosomal dominant ichthyosis is characterized by the presence of just few intact, or by complete absence of keratohyalin granules in the granular layer. The detected ultrastructural signs may be used in the differential diagnosis between various ichthyosis forms and may contribute to deciphering the pathogenetic mechanisms of impairment of keratinization in this hereditary dermatosis. PMID- 2588786 TI - [Intravital microfluorimetry of the skin]. AB - Life-time microfluorometry of the skin, carried out in 52 patients suffering from allergic dermatitis and eczemas, in 22 normal subjects, and in 10 patients with latent sensitization to nickel, chromium, and fluorides, has revealed a complex of changes of the primary and secondary fluorescence of the skin cells (keratinocytes and Langerhans' cells) and of the fluorescein transport in the skin. The authors suggest that life-time microfluorometry of the skin can be employed for the early diagnosis of allergic dermatoses in industrial conditions. PMID- 2588787 TI - [The cytological characteristics of Malherbe's necrotizing epithelioma]. AB - Histocytological examinations of 12 cases of Malherbe's tumor have made it possible to define the criteria of the cytologic diagnosis of this tumor and to distinguish the signs that permit its differentiation from related diseases. PMID- 2588788 TI - [Reasons for the neglect of skin melanomas]. AB - Reasons of neglected cases of skin melanomas are analyzed, with an emphasis on physicians' errors. PMID- 2588789 TI - [The use of chlorhexidine bigluconate in the combined treatment of patients with chronic generalized (granulomatous) candidiasis]. AB - .02% aqueous solution of chlorhexidine bigluconate has been used in the treatment of patients with chronic generalized candidiasis. Salivary pH values have been checked up over the course of treatment. The drug has been administered as a gargle or in applications 3-4 min 4-5 times daily for 10-12 days. Such treatment has completely cleared away the oral mucosa and tongue symptoms; this procedure has been followed by sanitizing of the oral cavity. PMID- 2588790 TI - [The clinical characteristics of patients with Reiter's disease]. AB - The authors analyze 46 case histories of patients with Reiter's disease. They describe the clinical, bacteriological, serological, and x-ray examinations and the features of the disease course. The majority (97.7%) of patients have developed the disease after casual sexual intercourse. Fifteen patients suffered from an acute disease, in the rest it coursed without manifest general symptoms. The principal and permanent symptom of Reiter's disease is urethritis complicated by prostatitis and vasculitis. The drugs for this disease are listed. The authors necessitate examinations and sanitation of the patients' sexual partners. PMID- 2588791 TI - [Gonorrheal lesions of the eyes]. AB - Analyzes the clinical features and methods for the diagnosis and treatment of gonorrheal ophthalmia in the newborns and patients with urogenital gonorrhea. PMID- 2588792 TI - [Clinical variants of Wegener's granulomatosis]. AB - A female patient is described, suffering from a lingering superficial form of Wegener's granulomatosis. The disease has been diagnosed on the basis of its prolonged (7 yrs) relatively benign course, isolated involvements presenting as skin and nasal mucosa ulcers, hard palate and nasal septum defect, and histologic shifts (necrotizing paling granulomas, combined with vasculitis). Low prednisolone doses have been quite effective in therapy of this condition. PMID- 2588793 TI - [Dipromonium in the treatment of scleroderma patients]. AB - Basing on the literature data on dipromonium biochemical and pharmacologic characteristics and on her own experience, the author has developed the treatment schemes with due consideration for scleroderma severity. The treatment has been associated with a reduction of glycosaminoglycan excretion with the urine, this correlating with the clinical improvement resultant from dipromonium therapy. PMID- 2588794 TI - [Late ulcerating cutaneous leishmaniasis]. AB - A female patient, aged 72, a resident of the endemic area in Uzbekistan, is described. She developed skin lesions on the face, resembling tuberculous involvement, two years before the condition has been diagnosed as cutaneous leishmaniasis with late ulceration. Leishmania have been isolated in laboratory studies. PMID- 2588795 TI - [Cancer of the glans penis]. AB - Carcinoma of the glans penis has been diagnosed in a patient aged 84 with a history of treatment for syphilis. The condition has been diagnosed on the basis of histologic studies. PMID- 2588796 TI - [A case of early neurosyphilis]. AB - A patient with secondary relapsing early neurosyphilis is described. PMID- 2588797 TI - [HLA and ceruloplasmin phenotypes in lupus erythematosus and circumscribed scleroderma]. AB - The incidence rates of combinations of A and B loci histocompatibility antigens in loci and haplotypes and of ceruloplasmin phenotypes have been examined in 137 patients with lupus erythematosus (LE) and scleroderma circumscriptum (SC). The studies have revealed that LE and SC are associated with certain haplotypes and HLA antigens combinations, this indicating the contribution of these phenotypes to the realization of the genetic predisposition to these diseases. In A1B8 haplotype carriers the disease is characterized by a benign course and manifests by integument forms of LE and scleroderma. IN A2B8 haplotype carriers the disease is more grave and presents as the systemic variant of LE. The third type of ceruloplasmin not detectable in normal subjects is usually associated with A9B18, A25B18, A3B27 haplotypes and with HLA A3A9 antigenic combination mostly in LE patients. PMID- 2588798 TI - [Proceedings of the 20th annual meeting of the Swiss Society of Pediatric Surgery. St. Gallen, 20-21 October 1988]. PMID- 2588799 TI - [20 years of the Swiss Society of Pediatric Surgery: retrospect and prospects]. PMID- 2588800 TI - [A conservative, surgery-delaying attitude in the treatment of concomitant hydrocephalus in patients with meningomyelocele]. AB - Between 1978 and 1987 5 out of 16 hydrocephalic patients with Arnold Chiari malformation and a meningomyelocele underwent a non-operative management. They showed normal mental development. Through meticulous clinical and neurological examinations as well as regular ultrasound and CT controls, it was possible to treat them conservatively. PMID- 2588802 TI - [Late results of sub-capital humerus fracture in children]. AB - From 1980 until 1984 56 children with a subcapital humeral fracture were treated at the Department of Paediatric Surgery in Zurich. 42 of them could be followed up 5 years after the accident, all showed a good result. In 21 children a simple immobilisation was successful. 8 cases needed a reposition of the fracture in anaesthesia and immobilisation. 11 cases needed further procedures, in 7 of them an osteosynthesis was done, in 4 cases an extension was necessary to hold the fracture position. One patient was treated primarily by open reduction and pinning of the fracture, another one by an extension. Both patients had polytrauma. The paper presents our long-term results and the different modalities of treatment are discussed in the light of our own results. PMID- 2588801 TI - [The clinical problem of the tethered cord syndrome--a report of 3 personal cases]. AB - Tethered cord syndrome is defined as a low state of the conus medullaris below the lumbar vertebra 2 after the neonatal period. Possible causes are: short thickened filum terminale, fibrotic ligaments, intradural lipomas. The clinical course is characterised by motoric and sensory deficits, disturbances of balance, neurogenic bladder disturbances, foot deformities and backache. A 3-year-old boy after operation of a lipomyelomeningocele at 2 months showed a one-sided leg shortening and a progressive neurogenic bladder and intestinal disturbance. The cause was a low state of the conus with a shortened filum terminale and a remainder of a lipoma. A 7-year-old boy after operation of a thoraco-lumbar meningomyelocele developed a progressive asymmetric paraspastic state with contractures. The neuro-radiological diagnosis of an intradural dermoid was verified on operation. A 10-year-old boy after operation of a covered lumbosacral meningocele showed a progressive backache which was connected with flexion. We found a low state of the conus through adhesions caused by scars which could be removed operatively. A collaborative treatment by the paediatric surgeon and the neuro-paediatrician of patients with dysraphic disturbances can prevent the severe consequences of the tethered cord problems with the co-operation and early intervention of the neuropaediatric surgeon. PMID- 2588803 TI - [Surgical treatment of distal humerus fractures in children]. AB - From 1955 to 1987 414 children with supracondylar fractures of the humerus were treated at the surgical department of the University of Erlangen. Most important for the choice of treatment in supracondylar fractures was the classification of Baumann. 33 children concerning stage I were treated with cuff and collar or cast. Out of 381 patients with stage II and III Baumann's extension was used in 352 children; 29 had to be operated. The operation was indicated in a further 56 children. 20 of these had a lesion of the condylus radialis, 18 of the epicondylus ulnaris, 8 children showed diacondylar, 3 transcondylar lesions, 3 children had injuries of the condylus ulnaris and 4 more children showed splintered fractures. In 234 patients a follow-up was carried out according to the scheme of Morger. In 91% there was an ideal or good late result, in only 2% of the patients the result was unsatisfactory. The majority of distal fractures of the humerus can be treated conservatively with good results; operative treatment does not improve the functional and cosmetic results. It is indicated in complicated forms of fracture, in which satisfying results are not to be expected by conservative treatment. PMID- 2588804 TI - [Intra-articular finger fractures in children]. AB - From 1982 to 1984 140 patients with fractures of the fingers were admitted to the department of surgery of the University Children's Hospital. Only 28 patients (21.5%) suffered from intraarticular fractures. Three 3/12 years later, 10 patients (35.7%) presented functional trouble or suffered from pain. Only 2 of the 15 conservatively treated patients had trouble. On the other hand, 8 children out of the 13 operatively treated patients presented an unsatisfactory result. Localisation, type of fracture and kind of treatment are analysed. We prefer as a rule conservative treatment excepting fractures of type Salter III and IV, osseous ruptures of the ulnar collateral ligament of the thumb and dislocated fractures. We suggest splinting with 0.6 mm K-wires. PMID- 2588805 TI - [Labor trauma-induced epiphysiolysis of the proximal femur. 4 cases]. AB - The authors report on 4 cases of obstetrical traumatic slipping of the upper femoral epiphysis. Firstly, they emphasise the difficulties of diagnosis because trauma is often missed. In two cases the delivery was a cesarean section (in the same clinic!). Wrong diagnoses are: --neonatal septic arthritis with swelling and inflammation of the hip, lateral deviation of the metaphysis on the x-ray. Nevertheless, there are no signs of an infectious disease and symptoms begin at birth. --congenital dislocation of the hip but clinical testing of stability is painful and doubtful. Secondly, when diagnosis is uncertain, a joint aspiration confirms haemarthrosis, and arthrography shows the displacement of the epiphysis on the metaphysis. Finally, the authors explain their therapeutic procedure: three times orthopaedic treatment with traction and spica cast for 2 months, a pin osteosynthesis in one case. Prognosis was favourable in two cases, but the two other cases present a lateral rotation of the leg in relation to a retroversion of the femoral head. PMID- 2588807 TI - [Y-ureterocutaneostomy in congenital hydroureter--causal therapy?]. AB - Between 1975 and 1987 30 patients with congenital hydronephrosis and megaureter were treated by Y-cutaneostomy according to Sober. 28 are still under our control. 5 of them showed normalisation of urine drainage. No further operation except the closure of the stoma was necessary. PMID- 2588806 TI - [Experiences with the early treatment of osteogenesis imperfecta]. AB - Between 1973 and 1988 twenty children with osteogenesis imperfecta were treated in the Department of Paediatric Surgery at the University of Berne, Switzerland. Our initial experience with the first 15 children, who had virtually no treatment during infancy and early childhood showed that they later developed severe soft tissue and skeletal deformities. Since resulting contractures and curvatures of the long bones are difficult to correct, we changed our therapeutic approach. Traditional therapy in OI was limited to the correction of bony malformations. Considering the fact, that the different elements of the locomotor system are part of a functional entity, we began early treatment combining physiotherapy and surgery. PMID- 2588808 TI - [Surgical treatment of renovascular hypertension in children]. AB - The main reason for renovascular hypertension in children is ideopathic fibrous and fibromuscular displasia. The pathogenetic classification of the disease was worked out in 1971 by Harrison and McCormac. Of all cases of hypertension in children between 5 and 20% are of renovascular origin. The illness demands an absolute necessity for treatment. The concept of management of renovascular hypertension includes the conservative treatment as well as angioplasty and especially the surgical reconstruction of the arteries. Nephrectomy should be considered as the treatment of last resort. For the surgical reconstruction of arteries a variety of techniques are available. Aortorenal bypasses using autologous arterial or venous grafts are expecially suitable in surgical treatment of renovascular hypertension in children. Results given in literature of the management of 334 children with renovascular hypertension and 8 own cases were evaluated by us according to the criteria of the National Heart, Lung and Blood Institute. In the majority of surgical treated children a substantial improvement in the state of health, or cure, could be achieved. PMID- 2588809 TI - [Sclerosing treatment with ethoxysclerol in anal prolapse in children]. AB - In 1980 we began the perianal injection treatment in children with anorectal prolapse. We can now report on 31 patients. In 1982 we reported on our first experiences with 6 children. We treat the children in hospital and inject aethoxysklerol mostly twice at an interval of three days. On the whole there were two relapses, both children were over 6 years old. A second injection treatment with the same method was again unsuccessful. In relation to the perianal cerclage according to Thiersch-Ombredanne - the method we used before - the injection treatment gives almost only advantages: Simple technique, shorter hospitalisation, fast healing without burdening the patients, no complications. PMID- 2588810 TI - [Heterotopic stomach tissue in the rectum and small intestine]. AB - We report on a case with ectopic gastric tissue in the rectum and on another one with this heterotopia in the small intestine. PMID- 2588811 TI - [A rare cause of rectal hemorrhage]. AB - Report of a patient who discharged water and doughy stools since birth. At the age of 2 yrs. 10 mo. he had terry stools, a perforation of the sigmoid was caused by an ulcer, the perforation was oversewn. Further discharge of liquid stools. Rectoscopy, endoradiography, rectal biopsy with identification of gastric mucosa. 99mTc-pertechnetate was accumulated in the rectal mucosa. At the age of 4 years, demucosation and pull-through was done. A cleft vertebral body and a finger shaped diverticulum were found and interpreted as sigmoid duplication. This is the only such case observed by us in 32 years. PMID- 2588812 TI - [Routine gastrostomy in esophageal atresia]. AB - Contrary to Kiely and Spitz we have been using gastrostomy in almost all cases of oesophageal atresia treated with primary anastomosis. Gastro-oesophageal reflux has never been a major problem and during 25 years of personal paediatric surgical experience we have never performed any type of antireflux surgery. To confirm this we have followed up 71 out of 77 survivors who underwent primary anastomosis and gastrostomy in 3 Departments of Paediatric Surgery. The patients were examined 13 months to 17 years, in average 7 years postoperatively. 50 children were free from symptoms, the remainder complained of increased susceptibility to broncho-pulmonary infections. These children were younger than 4 years. X-ray controls could be performed in 50 patients. The vast majority showed motility disorders of the oesophagus, well known as Yo-Yo-phenomenon with swaying of the dye and delayed clearing of the oesophagus. Distinct gastro oesophageal reflux was detected in 3 of the 50 cases, but there were no signs of oesophagitis or stricture and the patients were free of symptoms. There were no late strictures and no late mortality. We consider proper conservative management especially with oblique positioning as used in hiatal hernias most important in the treatment of the oesophageal motility disorder as well as gastro-oesophageal reflux in the early postoperative period and advocate routine gastrostomy and insertion of an endless thread for routine bougienage. PMID- 2588813 TI - Peritoneal drainage and ileostomy as a treatment for the acute necrotising enterocolitis. AB - Between 1982 and 1987, in the "Centre neonatal" of Rocourt (Belgium), 18 cases of necrotising enterocolitis have been operated upon during the acute stage of the disease. The authors explain the advantages and the disadvantages of the classical surgical procedures: laparotomy with exploration of the colon and resection of the necrotic segments followed by immediate reanastomosis or by enterostomy above the resected area. They recommend, however, a minimal laparotomy in the right lower quadrant with ileostomy on the terminal ileum without exploration of the colon or resection of the necrotic segments. The advantages of this technique are: minimal impairment of the general condition which increases the chances of survival; possibility to perform the resection later on when general and local conditions have improved; possibility for the lesions to heal spontaneously with short stenotic segments. Only 1 death among the 18 patients during the acute stage and none during the secondary procedures. In most of the cases, an economical resection could be performed with preservation of as much as possible of the normal bowel. PMID- 2588814 TI - [Improving anal continence performance by intensive continence training]. AB - Ten children of six to sixteen years with anal incontinence following anal atresia were treated with a conservative intensive continence training programme for a period of 6 to 18 months. The continence efficiency distinctly improved by an optic and acoustic biofeedback conditioning, transcutaneous electrostimulation of the pelvic muscles, by physical examinations and a sensibility training, as well as by contraction exercises. Not only the partial continence ability with low atresia but also the incontinence with high anal atresia could be improved to a level of continence, especially short-time continence. The essential success is based on an improvement of the strength and duration of the muscle contraction, of the sensible perception and of the nerval coordination of the pelvic muscles. After two weeks of therapy, 90% of the possible maximum increase had already been achieved. Thus, an evaluation of the training success was possible. This continence training programme proved an ideal supplement to surgical therapy. Even if other methods of therapy are exhausted, continence training is indicated for the improvement of anal sphincter function. PMID- 2588815 TI - [Complications following cell therapy]. AB - So far, the law in the Federal Republic of Germany still allows the injection of fresh-cell preparations from animals as a roborant to increase the vitality of the organism and to strengthen the body's immune defense system. The use of "sicca-cell" preparations was provisionally forbidden in 1987 by the Federal Health Organization (Bundesgesundheitsamt; BGA). Prohibition of fresh-cell injections would have exceeded the authority of this office, although the same serious reservations also applied in the case of this treatment method. Several publications that have appeared since 1955 have reported serious complications of this therapy, some life-threatening and some even lethal. Two further cases are now added: (1) A woman aged 69 had been receiving treatment with cell injections for 9 years. Immediately after an injection of sicca cells she collapsed and was hospitalized; 7 days thereafter she developed an ascending paralysis with increasing inability to swallow or breathe. She died 25 days after the injection as a consequence of central and peripheral respiratory failure. Autopsy revealed the alterations typical for acute Landry-Guillain-Barre-Strohl syndrome. (2) A 76 year-old healthy woman had been receiving treatment with fresh-cell preparations for several years. After an injection of cell suspensions a painful local swelling was observed. The symptoms were interpreted as the consequence of an iatrogenic local hematoma, and repeated punctures were performed to obtain blood. The patient was transferred to a surgical department for further therapy. Two days after the injection she suddenly died with signs of acute cardiovascular failure. Autopsy revealed the signs of a fulminating clostridial infection and also the characteristic signs of Landry-Guillain-Barre syndrome with involvement of the autonomic nervous system. In both cases the development of an inflammatory process in the peripheral nervous system could be interpreted as an immune mediated allergic disease, related to the repeated injection of heterologous antigenic material containing nervous tissues. This hypothesis would also explain the two other cases already published and would be consistent with the observed perivenous leukoencephalopathy of the central nervous system. The human disease pictures correspond to the well-established animal models of EAEM (experimental allergic encephalomyelitis) and EAN (experimental allergic neuritis). The pathogenesis is discussed; the major role of the central and peripheral nervous system is stressed, with special reference to the risk of acute autonomic failure. The need for specific autopsy techniques for the investigation of the entire nervous system, including spinal cord, roots, spinal ganglia and peripheral nerves with sympathetic chains, is raised. PMID- 2588816 TI - Study of postmortem blood circulation. AB - The objective of this work was to study the postmortem redistribution of blood volumes and its influence of the distribution of substances of different molecular weight (194.2 and 150,000 Da). Lipiodol Ultrafluide, Omnitrast, or a radioisotopic mixture of aminohippuric acid and human IgG were injected into the left ventricle of a total of 20 rabbits divided into three groups. Our results demonstrate the importance of related factors, including left ventricular postmortem contraction, the arterial vascular bed, diffusion processes connected to the physicochemical characteristics of the substances, and the anatomical distribution of the vessels. Postmortem diffusion of aminohippuric acid to the urine was observed. PMID- 2588817 TI - [Erythrocytes in cervical lymph nodes of the human as a sequela of stasis and/or lymph drainage. Questionable diagnostic significance in strangulation and mechanical injuries of the head]. AB - Information on the diagnostic significance of follicular hemorrhage and/or presence of red blood cells in the lymph node sinus was obtained by microscopic investigation of the superficial and deep human cervical lymph nodes. Fifty cases were selected on the basis of the following criteria: (1) cases without strangulation or mechanical head trauma; (2) cases in which death occurred by strangulation without additional mechanical head trauma; (3) cases without strangulation but with mechanical head trauma; (4) cases with strangulation and mechanical head trauma. The usual degree of stasis and hemorrhages and the dilation of the veins and/or capillaries are not sufficient to discriminate between cases with and cases without strangulation. Moreover, erythrocytes, erythrophages, and siderophages were encountered in the lymph node sinus of both cases with and cases without mechanical head trauma. Neither follicular hemorrhage nor the presence of red blood cells in the sinus is therefore diagnostically significant in forensic pathology. PMID- 2588818 TI - Plasminogen (PLG) polymorphism in northern Japanese: confirmation of PLG*M6 allele. AB - Plasminogen (PLG) phenotyping has been performed on 450 unrelated individuals from northern Japan, using wide-scale ultrathin layer polyacrylamide gel isoelectric focusing combined with immunoblotting. One common phenotype and six rare ones were observed. The rare phenotypes included the recently detected allele PLG*M6 in a new combination with PLG*M5 allele. The estimated allele frequencies for PLG*A, PLG*A3, PLG*M2, PLG*M5, PLG*M6, PLG*B, and PLG*B2 were 0.961, 0.009, 0.001, 0.016, 0.001, 0.003, and 0.009, respectively. PMID- 2588819 TI - Simultaneous identification and quantification of several opiates and derivatives by capillary gas chromatography and nitrogen selective detection. AB - A capillary column gas chromatographic method is described for the simultaneous determination of morphine, codeine, heroin, 3- and 6-monoacetylmorphine, nalorphine, naloxone, ethylmorphine, and naltrexone. The drugs were extracted from 2 ml plasma, urine, or other biological samples, including tissue under alkaline conditions in chloroform-isopropanol-n-heptane (50:17:33, v/v), with levallorphan as an internal standard. The drugs were extracted into acid and then reextracted into chloroform after the acid had been alkalinized. After derivatization with trifluoroacetic anhydride, an aliquot was injected into a 25m capillary column equipped with a nitrogen phosphorus detector. The lower limits of detectability, extraction recovery, and the within-run and day-to-day precision of results were determined for each drug. Our results indicate that the procedure is suitable for use in overdose screening and therapeutic drug monitoring. PMID- 2588820 TI - [Perfected, professional body-packing]. AB - A 27-year-old Columbian male was arrested in Aix la Chapelle at the border to Belgium, as he was suspected, of smuggling drugs in his body. Ultrasonographic and radiographic examinations revealed numerous packets in the colon descendens and the ampulla recti. After administration of laxatives, 70 packets were excreted that had been swallowed 3 days before in Bogota, Columbia. Each packet consisted of two rubber bags that were separately knotted with cord, layers of plastic foil, two further knotted rubber bags; the pressed core of cocaine was an average 3.8 cm in length, 1.9 cm in diameter, and 10.2 g in weight. The cocaine hydrochloride content ranged from 75.7% to 100%, with an average of 81.9%. The total net weight came to 714 g. Urine analysis revealed no cocaine metabolites, but metamizole and metamizole metabolites were present as a result of administration of Buscopan compositum during the flight to prevent premature excretion of the packets. PMID- 2588821 TI - Annotations to: "The effect of the THV bullet in animal tissue" by Peter J.T. Knudsen. PMID- 2588822 TI - [Papers on the occasion of an experts discussion on "Rheumatologic syndromes with bone diseases". 12-15 November 1987, Marrakech]. PMID- 2588823 TI - [Generalized osteoporosis in chronic polyarthritis]. PMID- 2588824 TI - [Assessment of patients at risk for osteoporosis using a risk factor analysis and quantitative computerized tomography]. PMID- 2588825 TI - [Special research topic 115 on "Psychosomatics, Clinical Psychology and Psychotherapy" in Hamburg. Selected results]. PMID- 2588826 TI - ["Comparative Research in Neurology and in Psychosomatic Medicine" special research topic 32--retrospect on a partial project (Giessen Test) from the viewpoint of a project leader]. PMID- 2588827 TI - [Basic knowledge in epidemiology: results of the incidence, distribution and follow-up of psychogenic diseases in the population. Special research topic 116 "Psychiatric Epidemiology" at the Heidelberg University]. PMID- 2588828 TI - [Psychotherapeutic processes: structure and results. Special research topic 129: 1980-1988. From the Psychosocial Center of Ulm University]. PMID- 2588829 TI - [Psychoanalysis and psychotherapy management in Austria]. AB - In a study on the psychotherapeutic provision in Austria the participation of the psychoanalysts was also researched. All over Austria there is a lack of psychotherapists in numbers and regionally. Long term psychotherapy except for a few special institutions are free of charge for the client. In private practice however the patients have to pay heavily. Non-medical psychotherapists are not eligible for refunds by the health insurance system. Almost 4/5 of all psychotherapists belong to a non-medical profession (e.g. psychologists). Only about 1/5 are medical doctors who work as psychotherapists on the basis of a therapeutic training. Psychoanalysts in Austria primarily work as psychoanalytic oriented psychotherapists and to a lesser extent as psychoanalysts. PMID- 2588830 TI - [Emergency series. 9. Emergency medications]. PMID- 2588831 TI - [Histomorphologic and catamnestic studies of 226 patients with cervical carcinoma in stage Ia in the years 1966 to 1986]. AB - All histological specimens obtained from patients with Stage-Ia cervical carcinoma, between 1966 and 1986, were re-examined and reclassified in a retrospective study for the purpose of checking on the validity of prognostic factors with relevance to cervical carcinoma at Stage Ia. The criteria valid at present were satisfied by 226 cases. No accurate sub-division by sub-groups Ia1 and Ia2 was possible by tumor measurement. Multicentric tumors were recorded in eight cases. Conisation proved to be an optimum approach to diagnosis of Stage-Ia cervical carcinoma. The percentual amount of histologically identified koilocytosis as an expression of preceding virus infections went up with significance from 13 to 34%. Maximum infiltration of 3 mm in depth was exhibited by 93% all tumours, while 5 mm infiltration was recorded by seven per cent. Significant correlations were found to exist between depth of infiltration, tumour volume, shape of growth, degree of differentiation, and involvement of lymphatic vessels. PMID- 2588832 TI - [The effect of formalin fixation on several properties of the brain]. AB - Described in this paper are the effects on formalin fixation of 106 human brains autopsied at a large neuropsychiatric hospital. Mass and volume of the brains changed considerably during a 3-week fixation period. On average mass increased by 50 g, volume by 57 ml. Mean brain density decreased during the first week and attained its final value almost at the end of the third week. Most changes seem to happen during the first week. Male and female brains behaved differently. Formulas to predict at autopsy time mass and volume of the brain after 3-week fixation in formalin are presented. Possible interpretations of our findings are discussed and compared with results reported by previous workers on this subject. PMID- 2588833 TI - Histochemical and histophysical detection and specification of foreign bodies in human tissues. AB - The authors summarize their experience from histochemical and histophysical detection of foreign bodies in 1,000 cases. Methods are described for the detection of metal particles, vegetable material, of mineral substances, plastics, and mineral greases. PMID- 2588834 TI - Leiomyomatosis peritonealis disseminata in a fetus. AB - A case of a female fetus born with multiple developmental defects and leiomyomatosis peritonealis disseminata (LPD) is reported. The authors suspect that similar etiologic factors may be responsible for both the developmental defects and LPD. PMID- 2588835 TI - [Problems in the documentation of autopsy findings on death certificates for stillborn babies and deaths of babies under one year of age]. AB - Analysis of 311 death certificates issued on stillbirths and deaths below one year of age, between 1979 and 1984, together with checks on all clinical data in them revealed a great number of erroneous entries by pathologists. These included using of wrong printed lines, reference to wrong ICD classes, disagreement between verbal notes and ICD code, statement of unimportant changes as causes of death, and mistakes in defining basic diseases. Error rates are reported and discussed. Pathologists quite often failed to take sufficient advantage of the possibility of stating a multicausative background of death. PMID- 2588836 TI - [Quality control in medicine. Analysis of death certificate entries with a personal computer]. AB - Important information obtained from autopsies may be statistically evaluated by means of decentralized data processing, using the personal computer. A method for precise evaluation of death certificates against autoptic findings is described in this paper. This computer-assisted approach facilitates statistical analysis of mortality and supports the accuracy of clinical diagnoses. PMID- 2588837 TI - [Problems of agreement of clinical and autopsy diagnoses]. AB - Results obtained from autopsy are parameters of importance to efficacy of diagnosis and therapy. To enable better overseeability of higher numbers of cases, the necessary congruence between clinical and postmortem diagnoses should be consistently settled on the basis of identical criteria used by clinicians and pathologists. Aspects relating to the problem are discussed in some detail, and suggestions are made on how to formulate final evaluations in postmortem reports. PMID- 2588838 TI - [Fracture of the tibial shaft--still a traumatology problem?]. AB - Diaphyseal fractures of the lower leg have continued to hold a special position in terms of incidence, type, severity, and frequency of typical complications as well as healing disorders. Despite general consensus regarding fracture healing and major factors of influence, there still is discrepancy of opinions and recommendations, in the context of pathophysiology, mechanics, and therapy. All in all, 302 fresh fractures and 134 cases of delayed healing or pseudoarthrosis in the diaphyseal region were treated, between 1971 and 1985. It has been the authors' experience that conservative treatment, according to the classical school, should be applied whenever possible. The trend in surgery, primarily for open fractures, is towards adequately dimensioned fixateur externe. Accurately defined minimum instability and healing with callus formation are nowadays appreciated and preferred. The fibula-ligament-membrane-complex may assume great importance to instable or defective forms of tibial fractures. Experimental and clinical investigations are likely to suggest that, depending on the individual case, the fibula should be included in the overall therapeutic concept, when it comes to impaired or delayed healing and pseudoarthrosis. PMID- 2588839 TI - [Results of the treatment of femoral and tibial fractures following interlocking nailing and plate osteosynthesis. A comparative retrospective study]. AB - The Howmedica lock nail was introduced to an ordinary hospital where femoral and crural fractures had been stabilised in the past almost exclusively by plate-type osteosynthesis. Since only minor change had taken place regarding surgeons and surgical environment, the decision was taken to compare two groups of patients with lock nailing and plate-type osteosynthesis. Most of the nailing patients could immediately expose the injured extremity to load. Hospitalisation for them was as short as twelve days on average. They were fit for work not later than six months from surgery. Plate-type osteosynthesis patients, on the other hand, were hospitalised five weeks, on average. None of the patients could fully use his or her leg, after two months. Pseudoarthrosis was quite frequent in the wake of plate-type osteosynthesis but was not observed at all after lock nailing. The risk of posttraumatic osteomyelitis was considerably reduced. Covered nailing proved to be applicable to the majority of cases. A specifically designed image converter was used in cases of distal locking. Lock nailing proved to provide a great number of advantages, with cost saving being one of them. It is a routine method that can be used at any general hospital, once the surgical team on the spot has been familiarised with the technique. PMID- 2588841 TI - [11th Congress of Emergency Surgeons of East Germany with international participation. 6-9 November 1988, Leipzig. Abstracts]. PMID- 2588840 TI - [Injuries caused by bicycle spokes in children]. PMID- 2588842 TI - [Surgical intervention in stenoses and aneurysms of the renal artery]. AB - Corrective vascular surgery was performed on 36 patients with renovascular hypertension and one patient with normal tension for 38 defective renal arteries, among them 58 per cent with arteriosclerosis and 35 per cent with fibromuscular dysplasia, in Jena, between 1969 and 1985. Follow-up checks were conducted six years from the operations (average) and revealed three major long-time results: Average blood pressure had declined from 211/121 mm Hg preoperatively to 152/95 mm Hg postoperatively. Renal functions were stabilised. Necessary antihypertensive medication could be reduced to 42 per cent of the preoperative values. Three revascularised kidneys had to be surgically removed in a second session. Four patients had died, the grey figure being one. Restenosation was recorded from three of 28 morphologically assessed arteries. Aneurysmal dilatation of a bridging graft was recorded in one case. Revascularisation proved necessary in another two. The point can be made that in cases of reno-arterial stenosis corrective vascular surgery has continued to be a valid therapeutic concept, adequate indication provided. It still is a real alternative to percutaneous transluminal angioplasty, nephrectomy or isolated therapeutic medication. PMID- 2588843 TI - [Reconstructive surgery in tracheobronchial injuries]. AB - The cause of traumatic tracheobronchial lesions are ruptures as result of blunt trauma, penetrating injuries, iatrogenic manipulations and aspirated fixed foreign bodies. Such lesions are relatively rare. Tracheobronchial lesions with clinical relevance were detected in an acceptable time after the trauma. Emergency tracheobronchoscopy is of great importance for the diagnosis. In the most of patients with bronchial ruptures we have been able to avoid a lung resection by the early operation with direct suture. PMID- 2588844 TI - [Surgical treatment of chronic bronchial foreign bodies and its complications]. AB - In the last 30 years five patients with foreign bodies from tracheobronchial tree were treated. In four cases the foreign body was not discovered. In all patients was necessary to carry out a lobectomy. PMID- 2588845 TI - [Infrared coagulation in lung surgery]. AB - Infrared coagulation (IRC) is a reliable method to stop surgical bleeding from the thoracic wall and proves to be superior to other forms of coagulation in this area. In pulmonary parenchyma IRC is used for sealing of parenchymal surfaces after atypical resections. Emphysematous bullae may be coagulated with IRC instead of over-swan. A main advantage in using IRC is that the surgical area not necessarily needs to be "dry" for application of IRC. Forced pressing of the IRC applicator against the tissue prevents dissipation of light energy via running blood. There are no superficial carbonisations, instead there is coagulation inside the tissue. PMID- 2588846 TI - [Chylothorax following pneumonectomy]. PMID- 2588847 TI - [Surgical therapy of anorectal abscesses and fistulas]. AB - Retrospective analyses were made of 171 of 200 patients on whom operations had been performed for anorectal abscesses and fistulas, between 1981 and 1985. For abscess exposure and deroofing, we tried to perform simultaneous fistulotomy, with no recurrence being recorded from 37 patients treated that way. The major courses of anorectal fistulas proved to be predictible in most cases. Surgical approach and postoperative management are described in some detail. Clinical records were evaluated together with a questionnaire, with particular reference being made to the type of fistula, susceptibility to recurrence, faecal continence as well as length of hospitalisation and certified absence from work. PMID- 2588848 TI - [Diagnosis and therapy of inflammatory cecal diverticula]. AB - Caecal diverticular are rare, and so are their inflammatory complications. The clinical symptoms of caecal diverticulitis are hard to distinguish from those of acute appendicitis. Caecal diverticulitis, therefore, is usually diagnosed intraoperatively. Reported in this paper is experience obtained by the authors from seven patients who had received treatment, in recent years, at the Surgical Department of the University Hospital of Heidelberg, FRG. An account is given of incidence, possible diagnostic approaches, and potential complications. Surgical management of caecal diverticulitis should be restricted to the smallest possible intervention. PMID- 2588849 TI - [Non-traumatic perforations of the small intestine]. AB - A series of 23 patients is reviewed admitted to our hospital for non traumatic perforation of the small intestine, a condition found very rarely as a cause of acute abdominal disease. The causes were primary small bowel neoplasia (four patients), adhesions (five patients), intraluminal foreign bodies (two patients), small bowel metastases (two patients), diverticulum (two patients). In seven patients a perforation was found that was neither related to any gross alterations of the bowel wall nor was specifically distinguished in histology. For the latter group, the possible role of local drug toxicity, especially of potassium chloride, is discussed. PMID- 2588850 TI - [Effects of roentgen contrast media containing barium sulfate on enterocutaneous fistulas]. AB - Fistulation in the wake of thoracic and epigastric interventions are conservatively treated, as a rule, because of the high rate of complications expected from reoperation. With properly functioning anastomotic transit, insufficiencies usually undergo spontaneous healing, within four to six weeks. Enterocutaneous fistulae developed in 29 of 271 patients with intrathoracic oesophagogastric or oesophagojejunal anastomosis. Syringeal ramification into pleural or abdominal cavities were ruled out by means of an absorbable contrast medium, before barium sulphate was orally administered to all patients. Thoracic fistulae were closed after 21.8 days on average, while 20.3 days was the average period required for closure of epigastric fistulae. Barium sulphate was found to exercise stimulating effects on fistular tissue granulation, so that obliteration of the fistular system occurred much sooner, as compared to conservative treatment. The patient's quality of life can thus be improved, and hospitalisation can be shortened. Neither locally delimited nor systemic complications were observed in any of the cases described. PMID- 2588851 TI - [Intestinal duplications in adulthood as a rare cause of acute abdomen]. PMID- 2588852 TI - [Intestinal loop incarceration in the drainage canal. A rare cause of postoperative ileus]. PMID- 2588853 TI - [The role of anxiety as a psychological co-factor in invasive treatment of sterility]. AB - To prove the importance of anxiety as a disturbing factor during invasive sterility therapy 87 women of an IVF- and GIFT-series were investigated by a standardized anxiety inventory. We could not find any direct relations between breaking off stimulation and a striking level of anxiety. The role of anxiety as a co-factor in the different kinds of sterility management will be discussed. PMID- 2588854 TI - [Treatment monitoring of patients with uterine cancer with and without progression by free serum amino acids]. AB - We determined 10 free serum amino acids by automatic chromatographic analyses in continuous steps in tumour monitoring of 51 patients with cancer of the uterine body. There were 39 patients without and 12 patients with recurrent disease. We found an elevation of aspartic acid, glutaminic acid, tyrosine and phenylalanine in continuous monitoring. Glycine, alanine, valine and leucine have an increased level in pretherapeutic value, too. A monitoring with amino acids in metaphylaxis is possible. PMID- 2588855 TI - [Correlation of cervicovaginal cytology and histology in endometrial cancer]. AB - Authors compared the results of 242 cytologic examinations of patients suffering from endometrial carcinoma with the histologic picture of the tumour. Conventional methods of cytodiagnostic screening in case of less differentiated tumours were found to give better results. Results of hormonal cytologic examinations demonstrate that there is an inverse relation between differentiation of tumour and maturity of vaginal epithelium. The authors analyze this observation with regard to the receptor theory of the malignant transformation of the endometrium. PMID- 2588856 TI - [Induction of labor with peroral tablets of PGE2-Prostin Upjohn]. AB - In the course of 12 months 141 deliveries were induced with peroral tablets of Prostin. Only patients with cervix score greater than or equal to 5 were induced after previous rupture of membranes Tablets were administered in the scheme of 1 2-3 in the intervals of 30 minutes. Further doses were applied according to the onset of uterine contractions and the development of side effects. The single dosis of 3 tablets was never exceeded. Successful induction was reached in 136 cases (96.5%), unsuccessful one in 5 cases (3.5%). Vomiting occurred in 15 cases. Neither uterine hyperstimulation nor any other serious side effects were recorded. The average consumption for successful induction was 12 tablets. PMID- 2588857 TI - [Prenatal diagnosis of complex abnormality syndromes. A case report]. AB - Two cases of complex and serious fetal malformations are presented, which have only been diagnosed in a relatively late stage of pregnancy. In both cases unspecific difficulties had already arisen during ultrasound screening, but they were not considered to be of any vital importance. The problems of diagnosing malformations by ultrasound and the serious consecutive consequences are discussed. PMID- 2588858 TI - [Why is blind suction of the mouth cavity of the newborn infant immediately post partum not recommended?]. PMID- 2588859 TI - [The validity of parameters in neonatal diagnosis and fetal monitoring of breech deliveries. 1. Neonatal status after breech delivery]. AB - By means of 522 singles in breech presentation the pH of umbilical artery (pH u. a.) and Apgar score in comparison to the mode of delivery, duration of pregnancy and weight of neonates have been analysed. The frequency of deliveries by cesarean section in breech presentation was 28.3%, the rate of preterms in these cases amounts to 14.6% and the perinatal mortality to 42.1%. The average value of pH u.a. after vaginal delivery (7.25) was significantly different to the value after cesarean section (7.28). 25% of the pH-values were below 7.20, 10% below 7.10. Mixed acidoses dominated, metabolic ones after vaginal and abdominal deliveries equalled each other. Vaginal deliveries were frequently followed by respiratory acidoses. In 81% of one-minute-Apgar and in 93% of five-minute-Apgar, the score was above 7. According to our experiences the only determination of the pH u.a. after breech deliveries is not sufficient, because of being at risk for the fetus it demands the measurement of the complete acid-base-status. A critical comparison of these data with the clinical status of the newborn is necessary. PMID- 2588860 TI - [The validity of parameters in neonatal diagnosis and fetal monitoring of breech deliveries. 2. Problems in fetal monitoring in the breech position--a proposal for a standardized biochemical diagnosis]. AB - By means of 149 fetal microblood samplings (FBA) from the breech in deliveries in breech presentation and by means of 64 cardiotocograms the validity of biochemical parameters and biophysical ones of fetal monitoring will be investigated. It takes an increased number of suspect or pathologic CTG into account in cases of breech presentation. By means of FBA it is possible to exclude or to confirm the supposed acidoses. By this the rate of operations during delivery can be reduced or the operation will be indicated respectively. A normal fetal pH resulting from the general biochemical monitoring does enlarge the obstetricians license when the fetus presents himself in advanced parturition in pelvic floor (hold back of breech during assisted spontaneous delivery). A pH less than 7.15 demands an immediate delivery. A prognosis of fetal outcome by means of FBA and CTG is not possible due to difficulties in calculation of the final stage of breech presentation. The difference between fetal pH measured in pelvic floor and pH in umbilical artery must be kept as small as possible and it might be regarded as criterion of the management of the delivery in breech presentation. PMID- 2588861 TI - [The effect of partusisten, dilatol, papaverine and magnesium sulfate on uterine smooth muscle in vitro]. AB - Inhibitory effects of Partusisten, Dilatol, Papaverin and Magnesium-sulfat on the activity of smooth muscle were tested in vitro on 18 isolated stripes of rats uteri, exhibiting both a high sensitivity against oxytocin and a distinct spontaneous activity. Minimal inhibitory concentrations of all drugs tested were determined, and their influence on the frequency and amplitude of contraction as well as on lag phase between inhibition and onset of spontaneous activity were registered. Basing on these experimental data conclusions were drawn concerning their clinical relevance. PMID- 2588862 TI - [Rectal examination during labor--tradition or compelling necessity?]. AB - 6,639 consecutive deliveries are followed up with respect to the course of puerperium. All these patients were examined during delivery vaginally. Febrile temperatures sub partu were to be stated in 1.1% and post partum in 2.0%. Subfebrile temperatures within the first 7 days of puerperium were to be seen in 7.0%, neonatal infections in 0.5%. The pro and contra of vaginal versus rectal investigation are discussed. The use of an emulsion containing chlorhexidine an antiseptic gliding substance is recommended for obstetrical examinations before and during labour. PMID- 2588863 TI - [Experiences with the antigestagen mifepristone (RU 486) in the interruption of early pregnancy]. AB - 50 healthy women (mean age 29.9 +/- 6.4 years) with early unwanted pregnancy (mean duration 39.3 +/- 2.9 days post menstruationem) received a single oral dose of 600 mg of Mifepristone. Uterine bleedings occurred in all patients within 8 to 110 hours (43 +/- 23.3 hours) after the application, but its duration was very different and correlated with the results of treatment. 39 patients reported on an amount of bleeding exceeding by far the menstrual strength. But in most cases this heavy bleeding lasted only 1-3 days. Frequency of complete abortion was 80% (40 women). 4 patients had an incomplete abortion, and in 6 women the pregnancy was unaffected by the treatment. "Medical abortion" provides a novel alternative to the surgical procedure and is fairly accepted by the patients. Its efficacy, however, should be improved by focusing on early pregnancies not exceeding 10 days after the expected menstrual period and, perhaps, the additional usage of low doses of prostaglandin E derivatives. PMID- 2588864 TI - [The extent of fetal heart rate accelerations associated with fetal body movements in relation to the duration of fetal body movement]. AB - The temporal relations between fetal body movements and associated fetal heart rate accelerations were shown as the ratios of duration of acceleration or acceleration amplitude and the duration of associated fetal body movements in 44 normotrophic and 40 hypotrophic fetuses (body weights within the 6th to 10th percentiles, n = 19, and less than or equal to the 5th percentile, n = 21) between the 36th and 40th gestational weeks. Related to the duration of associated fetal body movements, hypotrophic fetuses proved to have gradually smaller heart rate accelerations than normotrophic fetuses. Moreover, the acceleration parameters duration and amplitude were dependent on the relative duration of fetal body movements. Short fetal body movements were accompanied by fetal heart rate accelerations of relatively highest degree and vice versa. As a consequence, no comparison is possible between temporally different fetal body movements and their associated heart rate accelerations. Of the two acceleration parameters duration and amplitude, the inclusion of the accelerations amplitude in the above mentioned ratio yielded the most obvious results. Taking into consideration that fetuses with intrauterine growth retardation are often in a state of chronic hypoxia, the ratios of acceleration amplitude and durations of associated fetal body movements indicated different degrees of this metabolic situation. PMID- 2588865 TI - [The acridine orange test. A new parameter in assessing the fertilizing capacity of spermatozoa]. AB - Simultaneously with in vitro fertilization (IVF), the acridine orange (AO) test was performed on 51 patients according to the method of Tejada et al. This test allows a differentiation of spermatozoa with intact (double-stranded) and denatured (single-sanded) DNA. A significant relationship was demonstrated between the percentage of green-fluorescing (intact) sperm and the results of IVF. For both, the groups with (n = 40) and without (n = 11) fertilization of human eggs, a positive correlation was found between AO-test and sperm motility, and AO-test and normal sperm morphology. PMID- 2588866 TI - [Urodynamic results before and following vaginal electrostimulation in the treatment of urinary incontinence in the female]. AB - In this study we demonstrate our first experience with vaginal electrostimulation in the treatment of stress incontinence in women. In the group of 26 incontinent female patients there was described a very good effect in all cases (42%) and a slight improvement was noted in 9 cases (34%) at the same time. Our results correspond with other similar presented studies. The clinical improvement was verified in the urodynamic study. There were noted: the increase of maximal (P less than 0.05) and closure pressure (P less than 0.05) of the urethra, the increase of transmission factor (P less than 0.01) and of maximum of EMG activity of the sphincter (P less than 0.005), as well as an improvement of compliance of the bladder (P less than 0.01) and of volume in the first desire to void (P less than 0.01). We can conclude that this method of intermittent vaginal electrostimulation is suitable in the treatment of female stress incontinence. PMID- 2588867 TI - [The protective effect of preparations made from plant seedlings in experimental Pseudomonas aeruginosa infection]. AB - The influence of preparations obtained from oat and wheat seedlings (immunostimulating factors IF-1 and IF-2, respectively) on the natural resistance of mice to P. aeruginosa infection was studied. IF-1 and IF-2 were introduced intraperitoneally in a single injection in doses of 100 micrograms and 1000 micrograms per mouse 2 and 7 days prior to the inoculation of P. aeruginosa strain 8 in doses of 1 and 10 LD50. The presence of substances capable of stimulating the immunobiological reserves of the body in actively growing plants (seedlings) was shown. PMID- 2588868 TI - [The frequency of the production of toxic-shock exotoxin by Staphylococcus aureus strains isolated in the USSR]. AB - 515 S. aureus strains, isolated from carriers and patients with staphylococcal infection in different regions of the USSR, were studied. Of these, 52.2% were found capable of producing exotoxin of toxic shock (ETS). The occurrence of the capacity for ETS production was the same among the strains isolated from the upper respiratory ways of carriers and from the purulent inflammatory foci of patients and little varied in staphylococci isolated in different regions. The study revealed that in strains sensitive to the typing phages of the International Set the capacity for ETS production occurred considerably more frequently than in nontyped cultures. No essential differences with respect to this sign between strains belonging to different phage groups were established. PMID- 2588869 TI - [A new rabies vaccine in public health practice in the USSR]. AB - A new antirabies vaccine prepared on the basis of virus grown in the ovine brain, purified from 85-90% of brain-tissue ballast substances and inactivated with beta propilactone has been developed at the Moscow Research Institute of Viral preparations (USSR Acad. Med. Sci.). The preparation produces no neuro-allergenic effect in tests on guinea pigs. When injected to humans, the vaccine shows much lower reactogenicity than Fermi vaccine. High antigenic and immunogenic activity of the new vaccine has made it possible to work out a less intensive immunization schedule in comparison with that used for immunization with Fermi vaccine and nonconcentrated tissue-culture vaccine, viz. doses of 3 ml for 12 days or doses of 3 ml for 20 days with two booster immunizations. The preparation has been introduced into medical practice. PMID- 2588871 TI - [Changes in the immunotropic activity of neutrophilokins in the course of experimental staphylococcal infection]. AB - The influence of the products secreted by activated neutrophils (neutrophilokins) of mice, both intact and infected with staphylococci, on the activity of mouse spleen cells in the graft-versus-host reaction, immune response to sheep red blood cells and the antigen-presenting function of peritoneal macrophages was studied. Neutrophilokins of intact mice stimulated the activity of immunocompetent cells. Neutrophilokins obtained from infected mice on day 3 after infection produced an immunosuppressing effect. On day 7 after infection the immunostimulating activity of neutrophils was restored and showed practically no difference from the normal level. PMID- 2588870 TI - [The creation of specific immunity to staphylococcal infection in newborn infants by the intranasal administration of adsorbed staphylococcal anatoxin]. AB - The possibility of enhancing specific immunity in newborn infants by the intranasal administration of adsorbed staphylococcal toxoid to infants with a high risk of staphylococcal infection in doses of 1 drop (0.05 ml) into each nostril during the first 7-9 years of their life. On days 7-9 the level of anti alpha-toxin in the blood rose to 3.8 +/- 0.14 I. U./ml and remained sufficiently high 3-6 months later. When this method was used for the simultaneous immunization of mothers, their antitoxic titers were not as high as in newborn infants. No side effects were observed. In the control group, the titers of anti alpha-toxin were low during the whole period of observation. Infants immunized by the proposed method had no staphylococcal infections both during the newborn period and within the first year of their life. In the control group, 8 cases of minor forms of purulent septic infection were registered during the newborn period, and in 2 infants umbilical staphylococcal sepsis was diagnosed. PMID- 2588872 TI - [The cellular link in the immune response in the dynamics of experimental infection caused by influenza A viruses with various properties]. AB - The development of the cell-mediated element of immunity in mice in the course of experimental influenza caused by the virulent and avirulent (ts-mutant) variants of influenza A virus was compared. The strains under test were also found to differ in their capacity for reproduction in pulmonary tissue, which could be determined for the mutant variant A/PR/8/59/1 (with 5 ts-mutations in genes P2, P3, NP, NA and M) only at an effective dose of 7.5 lg EID50. In mice infected with the initial and ts-variants of influenza A virus the formation of all mechanisms of the cell-mediated and humoral elements of immunity (natural killer activity, antitoxic T-lymphocyte activity, antibody-dependent cellular cytotoxicity, virus-specific antibodies) occurred. The curves showing the dynamics of the formation of cytotoxic mechanisms had a phasic (cyclic) character in all forms of the infectious process under study (lethal, sublethal and poorly reproductive). A dose-dependent effect on the character of the formation of these mechanisms was registered; besides, at the later period of observation (till day 14) the presence of activity was noted when the infectious virus was not detected, which may serve as an additional evidence of the prolonged expression of the viral genome in the body of the host. PMID- 2588873 TI - [Variants of the agglutination reaction: the present and future]. AB - The methodological analysis of the main problems of serological diagnosis has made it possible to pick out the tests of the agglutination type, especially those made with the use of sensitized erythrocytes, as most suitable for mass use. The comparison made between different agglutination tests has confirmed the fact that the use of sensitized erythrocytes in such tests is highly effective. The comparison of the diagnostic possibilities of agglutination tests involving the use of erythrocytic reagents with those offered by enzyme immunoassays has demonstrated that tests based on the phenomenon of passive hemagglutination have great possibilities and hold considerable promise not only for mass immunological surveys, but also for research work. PMID- 2588874 TI - [Immunomorphologic aspects of local (wound) revaccination with tetanus anatoxin]. AB - The immunomorphological reaction of regional lymphoid organs, the pathomorphology of wound tissues, humoral antitoxic response and a protective effect after local (wound) booster immunization with tetanus toxoid have been studied in observations on 100 guinea pigs with experimental wound infection. The study has shown that the local application of tetanus toxoid, besides stimulating humoral response, induces a more rapid effect aimed at the primary elements of the infectious process (the germination of spores, the adhesion, colonization and toxin formation of the causative agent), thus facilitating the localization of the focus of infection, the development of reparative processes in the wound and the arresting of the infection. PMID- 2588875 TI - [A comparative study of the fibronectin-binding capacity of staphylococci]. AB - The comparative study of the fibronectin-binding capacity of S. aureus and S. epidermidis of clinical etiology was carried out. Fibronectin binding was evaluated by original methods: the indirect hemagglutination test and the passive coagglutination test. In this study the occurrence of S. epidermidis isolates, as well as their level (evaluated by the titer) of fibronectin binding, was shown to be lower than those of S. aureus isolates. Fibronectin-binding representatives of S. epidermidis lost this capacity after storage in semiliquid agar at 4 degrees C for 2 months. PMID- 2588876 TI - [Electrophoretic study of the outer membrane proteins of leptospirae]. AB - The outer membranes of pathogenic and saprophytic leptospires have been isolated. The spectrum of outer membrane proteins in three saprophytic and one pathogenic Leptospira strains has been studied by means of electrophoresis in polyacrylamide gel. In Leptospira strains VGNKI-6 (pathogenic) and G-80 (saprophytic) identical proteins, as well as proteins similar in their Rf value, have been detected. The possibility of using strain G-80 for the development of leptospiral vaccine against serovars having common surface antigens with this strain has been suggested. PMID- 2588877 TI - [The effect of enterococci on normalizing the intestinal microflora in experimental dysbacteriosis]. AB - The normal microflora of the intestine produces essential influence on the vital activity of the host. The exposure of the body to the action of different unfavorable factors (roentgen radiation, the administration of antibiotics, Salmonella infection, etc) results in changes in the normal microflora of the gastrointestinal tract. This work was aimed at the study of the influence of Streptococcus faecium YDC-48 on the intestinal microflora of mice in experimental (chemotherapeutic, postirradiation) dysbacteriosis and Salmonella infection. The effect of the oral administration of S. faecium YDC-48 on the correction of the intestinal microflora of mice in cases of dysbacteriosis etiology was studied. The intragastric administration of S. faecium YDC-48 was found to induce an increase in the level of lactobacterin and a decrease in the number of opportunistic microorganisms in chemotherapeutic and postirradiation dysbacteriosis. The oral administration of S. faecium YDC-48 decreased the manifestations of intestinal dysbacteriosis in experimental Salmonella infection. The possibility of developing a preparation on the basis of S. faecium YDC-48, a representative of normal intestinal microflora, is discussed. PMID- 2588878 TI - [The use of the potentials of the molecular hybridization of nucleic acids as a method for the laboratory diagnosis of influenza in research on vaccinal infection]. AB - The data obtained as the result of the complex examination of volunteers immunized with live influenza vaccine, type A (H3N2), showed that the determination of the RNA-containing structures by the method of the molecular hybridization of nucleic acids (MHNA) was highly sensitive and reliable. This method proved to be more sensitive than common laboratory diagnostic tests (the isolation of the virus in chick embryos, the analysis of seroconversion, the antibody fluorescence test) and was not inferior to the complex of clinical tests based on the analysis of microsymptoms. The reliability of the positive (according to the data obtained by MHNA) results was very high: not less than 85% of them were confirmed by other tests. PMID- 2588880 TI - [Cases of occupational infection with the human immunodeficiency virus in the USA]. PMID- 2588879 TI - [A comparison of the spectra of antibodies to individual proteins of the human immunodeficiency virus in seropositive sera collected in the territories of the USSR and England]. AB - Antibody spectra to individual proteins of human immunodeficiency virus (HIV) in 74 seropositive serum samples collected in the USSR and 65 serum samples collected in Britain were studied by immunoblotting techniques. Most of the sera belonged to clinically healthy persons, some of the sera collected in Britain contained specific IgM antibodies. The results were evaluated qualitatively and quantitatively. In the former case the study of samples collected both in the USSR and in Britain yielded similar results which also coincided with the data of literature regarding asymptomatic virus carriers: very high content of antibodies to protein gp41 and sufficiently high content of antibodies to protein p24 were registered in all sera. But the quantitative evaluation of the results of this investigation revealed differences between serum samples collected in these two countries. The main feature of sera collected in the USSR was their noticeably greater reactivity with respect to the products of HIV gene gag: proteins p24, p53 and p22. The explanations of this phenomenon are discussed. PMID- 2588881 TI - [An analysis of the work and tasks of the microbiology laboratory at a multidisciplinary research institute]. AB - The comparative analysis of the work of 3 groups of microbiologists at a multiple discipline clinical research institute has permitted the development of the method for the evaluation of the work of researchers in the microbiological laboratory. The volume of investigations carried out in the laboratory, the relative significance of individual samples of clinical material, the degree of contamination of the samples under study, the level of the identification of microbes and the analysis of the data obtained in the course of investigations have been used as evaluation criteria. The method may be used for the objective quantitative evaluation of the work and the level of professional training of individual researchers, as well as for the calculation of expenditures in materials and time, necessary for performing investigations. According to the data of the analysis carried out by the authors with the use of the proposed method, the work of scientific-practical groups at the institutions of this category holds the greatest promise. PMID- 2588882 TI - [Quantitative research on the cyclic fluctuations of the epidemic process in a number of infectious diseases in Bulgaria]. AB - The cyclic nature of the epidemic process in Bulgaria was studied by various methods (spectral analysis, etc.), forming a system. The morbidity dynamics in 10 infectious diseases (scarlet fever, rubella, measles, epidemic parotitis, whooping cough, diphtheria, typhoid fever, enterocolitis, bacterial dysentery, viral hepatitis) over the years of 1909-1983 were studied and cycles covering the periods of 3-4, 5-6, 10-11 and over 16 years were established. The data on the relative part of cyclic processes in the registered morbidity of infectious diseases, as well as information on the prognostication of the spread of infections in the absence of vaccinal prophylaxis, are presented. PMID- 2588883 TI - [The epidemiologic classification of plague morbidity]. AB - On the basis of the analysis of plague morbidity in the world in the XX century all epidemic foci are subdivided into 3 groups: primary, indirect primary and secondary. Each group is characterized by its specific type of morbidity in accordance with infective factors: factors connected with the natural foci of infection in group 1, economic and synanthropic factors, as well as laboratory infections, in group 2 and anthroponotic factors in group 3. In its turn, each type of morbidity differs in routes, sources, mechanisms and clinical forms of infection. In accordance with the conditions of infection, the natural foci of plague can be subdivided into mono-, oligo- and multifactor foci. The typing of plague morbidity facilitates more target-oriented organization of antiplague measures. PMID- 2588884 TI - [Patterns in the antigen-nonspecific modulation of the B-cell activity in mice under the influence of a purified staphylococcal anatoxin]. AB - Purified staphylococcal toxoid (PST) has been shown to be an antigen-nonspecific immunomodulator, capable of inducing changes in the immune response of B-cells to unrelated antigens, such as sheep red blood cells (SRBC), in a wide range of doses (from 15 to 0.15 binding units per mouse). The manifestation of the immunomodulating effect depends on the conditions of the experiment: the doses of PST and SRBC, the age of mice, the sequence of the injections of the antigens and the intervals between the injections. The simultaneous injection of PST and SRBC induces, as a rule, an increase in immune response to the test antigen, while their separate injection induces mainly immunosuppression. PMID- 2588885 TI - [Immune depression--a possible cause of the unfavorable course of pneumonia in chronic alcoholics]. AB - In 27 patients, suffering with chronic alcoholism and hospitalized for pulmonary diseases in the Clinic of Pulmonology and Phthisiology, the following immunological characteristics were checked up: the functional activity of polymorphonuclear leukocytes and in 12 patients also that of alveolar macrophages were evaluated on the basis of the study of the phagocytic index and the phagocytic number, myeloperoxidase and the nitro blue tetrazolium test; the levels of serum IgG, IgA and IgM, the titer of the complement, E-rosette-forming cells (active and total) were also evaluated; the deficiency of cell-mediated immune response was determined by means of intradermal tests with the use of P.P.D., phytohemagglutinin, candidin, trichophytin. In all these investigations the depression of the functional activity of polymorphonuclear leukocytes and alveolar macrophages, dysimmunoglobulinemia, the increased level of circulating immune complexes and the suppression of cell-mediated immunity characteristics were revealed in the patients. Frequent infections and the severe course of bacterial and viral infections observed in such patients can be probably attributed to deficient cell-mediated immune response and to disturbances in phagocytosis. PMID- 2588886 TI - [The immunomodulating action of microwaves in the induction of an immune response to Vi antigen]. AB - In this work the possibility of using microwaves for immunomodulation in the immunization of animals with thymus-independent antigen was studied. The projection zones of the thymus and adrenal glands of the test animals were subjected to the action of decimeter, or ultrahigh frequency (UHF), waves, while the corresponding zones of the control animals were subjected to imitation UHF irradiation. Vi-antigen was shown to be a thymus-independent antigen for rabbits (according to the results of the evaluation of the functional state of thymocytes, as manifested by the adsorption of acridine orange by the chromatin of thymocyte nuclei and by the content of RNA and DNA in the thymus). The action of UHF waves on the projection zone of the thymus was accompanied by a decrease in the glucocorticoid activity of the adrenal cortex, observed simultaneously with a pronounced immunostimulating effect. The UHF irradiation of the zone of the adrenal glands was accompanied by immunosuppression in combination with enhanced glucocorticoid activity of the adrenal cortex. PMID- 2588887 TI - [Clinical manifestations of oligophrenia with fragile X syndrome in boys in the pre- and post-pubertal age]. AB - Psychopathological, neurological and somatic manifestations of oligophrenia-with fragile X chromosome were investigated in 13 mentally retarded boys in prepuberty and in 9 such post-puberty++ patients. Age-related features of several psychopathological and somatic signs of the disease were revealed. The authors discuss the possibilities of clinical diagnosis of the disease and stress the importance of its early cytogenetical diagnosis in mentally retarded males. PMID- 2588888 TI - [Clinico-physiological and evolutional aspects of the prevention of prenatal lesions of the fetal nervous system]. AB - Two hundred fetuses were studied under parturition and consequently the newborn children were investigated with special reference to analysis and prevention of fetal nervous system affections. In line with the concepts of the physiological polymorphism+ of beginning and course of labor, the theory of fetal prenatal hibernation and autoanalgesia in parturients taking into account the obstetricians' experience in labor assistance, the authors validate some suggestions aimed at preventing prenatal fetus CNS infliction. PMID- 2588889 TI - [Skin resistance reaction to alcohol-related verbal stimuli in alcoholic adolescents]. AB - In 25 patients with early alcoholism and 28 adolescents with initial experience with alcohol the skin conductance responses were tested under a range of stimuli. In the patients, the orienting responses to alcohol-relevant verbal stimulation were stronger and later extinguished as compared to normals suggesting higher subjective values of these words. The responses were increased in abstinence and directly depended on its duration. Indirect evidence pointed to the relation of psychophysiological indices to the craving to alcohol. The authors inferred that orienting response to alcohol-relevant stimuli can be a tool in the studies of alcoholism. PMID- 2588891 TI - [Spectrum analysis of the EEG in children and adolescents with epilepsy: general characteristics and pathophysiological interpretation of the data]. AB - Spectral EEG analysis (fast Fourier transform) was performed in 48 patients with epilepsy, 4 patients after one epileptic seizure, 12 sibs of epileptic patients, 18 children with febrile convulsions, 18 patients with vasoautonomic dystonia, and 23 normal children. Means, standard deviations, standard errors of the means were calculated for the spectra. A distinct EEG type was found characteristic of the epileptic patients: power increase by the factor of 5 to 10 as compared to normals, predominantly in theta band. This EEG type was shared by epileptic patients and their sibs. Both had peculiar patterns on hyperventilation. PMID- 2588890 TI - [Characteristics of narcotic and toxic substance abuse by adolescents (clinico sociological study)]. AB - The results of clinico-sociological investigation of 400 adolescents registered in Moscow narcological dispensary wards for abusing toxic and narcotic drugs are presented. The peculiarities of neurological signs were noted for different terms of abusing. Age-related sexual life of the patients was analyzed with the peculiarities of their microsocial environment. PMID- 2588892 TI - [Possibilities of the diagnosis and the evaluation of epilepsy risk based on the data of EEG spectrum analysis in children and adolescents]. AB - Using spectral analysis data of the previous study a trial was undertaken to develop criteria for diagnosis and risk assessment of epilepsy. To the spectral parameters++, differentiating groups of epilepsy and normals, the diagnostic weights from 1 to 10 were attributed, according to the probability "p" from 0.01 to 0.001 using "t" criterion. Sums of the weights formed "epilepsy indexes" (EL) for each normal and patient. From these EI confidence intervals for p less than 0.034 and less than 0.003 were obtained. The criteria were checked on a mixed group of patients differing by the degree of epileptic charge. Positive EI were found only in the patients with high risk of epilepsy (febrile convulsions and epileptic siblings) and in patients with actual epileptic seizures, corresponding in the latter mostly to p less than 0.003. PMID- 2588893 TI - [Complex stimulation of the locomotor and psycholingual develop- ment of children with perinatal lesions of the central nervous system]. AB - In 121 children with perinatal CNS damage a combined therapy was performed including, besides routine drug treatment, imitation stimulation of age-matched posture-++-tonic attitudes and motor skills, metameric reflexotherapy aimed at the CNS region lesioned, magnetotherapy, electric laser puncture targeted at correction of dysfunctioning brain structures. Treatment efficiency was controlled by the brain "development profile" derived from formalized neurological and neuropsychological investigations, and electroneuromyography. The efficiency of the therapy was considerably decreased by the 3rd semester of life. PMID- 2588894 TI - [Clinical characteristics of the convulsion syndrome in newborn infants]. AB - A total of 272 mature newborn babies with perinatal neurological pathology and convulsive syndrome were studied. EEG, USI, diaphanoscopy, CT, blood tests for glucose, Calcium, Magnesium, bilirubin, pyridoxal-5-phosphate were performed. Cerebral structure was changed in 50.8 of the patients, and metabolic disorders detected in 13.8%. The recommendations were offered for the therapy of convulsive syndrome in newborns with due account of the above stated disorders. PMID- 2588895 TI - [Characteristics of the clinical course, pathogenesis and treatment of torsion dystonia in childhood]. AB - A total of 150 patients, predominantly children, with torsion dystonia++ (TD) were investigated. Their clinical syndromes, pathogenesis and results of treatment were analyzed. Prominent features were interfamilial (true heterogeneity) and intrafamilial clinical polymorphism of the disease. Autosome dominant++ type of inheritance was found in 15 families and the autosome recessive in 10. With respect to the clinical syndrome, 2 forms of TD were singled out: dystonic-hyperkinetic++ and rigid. These were different in the neurotransmitter metabolism. Long-term follow-up of the patients (2 to 20 years) proved a high efficiency of treatment with low doses of DOPA-containing drugs in rigid forms of TD. PMID- 2588897 TI - [Hereditary diseases and developmental disorders of the nervous system in children (clinico-epidemiological study)]. AB - These are data of a clinico-epidemiological investigation into dysontogenesis++ and inherited disorders of the nervous system in children in a major industrial region. The peculiarities of structure, rate, clinical picture, genealogy of the disorders in the population is described. A program of further actions is designed in order to elaborate a complex of preventive measures. PMID- 2588896 TI - [Use of functional biofeedback in the treatment of children with locomotor disorders]. AB - The results of out-patient application of functionalbiological- control portable devices in various static-kinetic+ disorders in children are reported. Repeated biotraining sessions combined with conventional therapy (drugs, physiotherapy, massage, physical exercises) were more effective than conventional means alone. PMID- 2588898 TI - [Acute traumatic intracranial hematoma in children]. AB - The data on 25 children patients with acute traumatic intracranial hematomas are presented. This accounts for 2.9% of a total of intracranial hematomas and 0.6% of a total of children with craniocerebral trauma. Correct diagnosis and early surgical intervention combined with therapeutic measures ensured favorable outcome in 76% of the cases. PMID- 2588899 TI - [Paralysis of external oculomotor muscles in children with infectious-allergic polyradiculoneuritis]. AB - Clinical investigation of 42 children with infectious-allergic polyradiculoneuropathy (Guillain-Barre syndrome) revealed that pareses of lateral ocular muscles were present but in patients older than 5 years. The pathogenesis and differential diagnosis between Guillain-Barre and Tolosa-Hunt syndromes is discussed. PMID- 2588900 TI - [Mental health status of young children (clinico-epidemiological study)]. AB - The work is based upon a combined prospective investigation into an urban children population aged 0 to 4 years by a group of psychiatrists, neurologists, psychologists and an expert in neurophysiology. The age group under investigation showed a high incidence of mental disorders (10% on average). The authors have singled out some major lines of clinical research into the mental disorders and micropsychiatry including a number of practical issues of improving special therapeutic-preventive assistance to children population. PMID- 2588901 TI - [A method of studying the visual evoked potentials in the evaluation of the status of the central nervous system in newborn infants]. AB - In 15 healthy mature babies and 15 newborn babies with cerebral pathology the visual evoked potentials (VEP) were investigated. The light diodes were used for stimulation. The curves preprocessed using a simple configurations technique were analysed with an euristic technique on a microcomputer. The high information value (88.5%) was attributed to VEP in cases of perinatal brain lesions. This suggested the inclusion of VEP techniques into the routine neurological investigation of the newborns. PMID- 2588902 TI - [Genetic classification of clinical forms of childhood schizophrenia]. AB - In an analysis of 225 families of probands with different forms of the course of children's schizophrenia, a hypothesis on the degree of their genetical similarity (or dissimilarity) was tested. Malignant and slow progredient form of children schizophrenia showed major genetical similarity (correlation coefficient 1.0) with the recurrent schizophrenia occupying a separate position having no common genetical predisposition factors with nuclear forms of schizophrenia. Paroxysmal progredient schizophrenia displayed a distinct genetical relation to any other form (genetical correlation coefficient ranging in 0.5-0.7). PMID- 2588903 TI - [Classification of the course of childhood schizophrenia in the light of long term follow-up]. AB - The work deals with the catamnestic substantiation of the systematics of schizophrenia in children. A group of 328 patients was selected in 1982-1987 from a cohort of schizophrenic patients studied in 1962-1972 in which the onset of the disease fell on their first 5 years. The stability of the course patterns was evidenced in the early childhood schizophrenia. A set of subspecies of disorders similar to schizoactive psychoses and peculiar affective schizoid states was differentiated out of the general pool of slow progredient and attack-like schizophrenia. This allowed to prove the notion of the whole continuum of endogenous psychoses in not only adults but also in children. PMID- 2588904 TI - [Autonomic vascular asthenia as a component of the psycho- autonomic syndrome in slowly progressing schizophrenia and cyclothymic disorder in young patients]. AB - Investigated were 55 patients with slow-progredient schizophrenia and cyclothymia aged 17 to 25 with the syndrome of vaso-autonomic dystonia (VAD) accompanying their mental disorder. VAD was found in 80% of the depressive cases, hypomaniac syndromes and psychopath-like (residual) states. Each of these disorders correlated with a distinct type of VAD. In a majority of the cases VAD manifested after several years of mental disease. The study provides grounds for combined psychotropic and rational psychotherapy with an early social rehabilitating assistance. The study substantiated the necessity of psychiatric services aimed at specialized psychiatric aid to these patients in the general out-patient clinic network. PMID- 2588905 TI - [The course of protracted reactive depression in young children]. AB - Clinical-dynamic and catamnestic techniques were used to study 34 children with protracted reactive depression developed as a response to their maladaptation to the nursing house conditions. The following stages of the disease were singled out: I, acute affective-shock responses; II, subacute reactive depression; III, protracted polymorphic depressive-neurotic state; IV, regress of the disease, compensation; V, post-reactive++ state, the outcome of the psychogenic disorders. The psychopathological and psychological characterization of each stage was performed. Some of the "background" factors appeared as determinants of the course and outcome of the disease. PMID- 2588906 TI - [Clinical aspects of paroxysmal states in children with depression]. AB - In 81 depressed children aged 3 to 14 years the nonepileptic attacks could manifest the different psychopathological phenomena: 1, headaches before and after spells, non-systemic++ vertigo with imbalance and oculovestibular events with or without loss of consciousness; 2, orthostatic symptoms, syncope, cataleptoid seizures, Kloos seizures; 3, depersonalization and derealization episodes, deja vu and jamais vu states; 4, attacks with pain in the stomach and other organs, various other autonomic signs; 5, unsteady neurological signs: pareses, sensory, visual and speech disorders; 6, nightmares, oneiroid states, sleep-walking; 7, convulsive states, hyperkinesis; 8, psychomotor excitation and inhibition states; 9, behavioral spells with aggression. These states are differentiated from epileptic and hysterical attacks. PMID- 2588907 TI - [Neurosonography of the brain in infectious toxicoses in infants]. AB - Brain neurosonography was performed in 15 babies with toxicosis-+-linked nervous disorders. Three types of the brain structure were established in the patients: 1, marked brain swelling in all patients; 2, concomitant perinatally induced brain structures' changes; 3, intracranial hemorrhage focuses resulting from the DIC syndrome. The technique is useful for precise diagnosis and prognosis of the outcome of the neurotoxic coma. PMID- 2588908 TI - [Alalic syndromes in deaf children]. AB - Clinical and experimental psychological investigation of 92 deaf children with various forms of mental dysontogenesis made it possible to single out a clinical group of deaf children with steady speech underdevelopment due to cerebral defects of residual-organic genesis and hereditary etiology. The features of the structure of intellectual defect are shown together with changes in emotionality and personality characteristic of deaf alalics. Singling out the pathognomonic features of intellectual and affective personality spheres can meet the needs of differential diagnosis of alalic syndromes from other clinical forms of mental underdevelopment in children with inherited and early acquired deafness in order to provide an adequate medico-pedagogical++ correction of these disorders. PMID- 2588909 TI - [Impulse control disorders in adolescence]. AB - This is an attempt of precise definition of the notion "drive disorders". An original definition is offered which differentiated these from related states. Based on the analysis of 76 clinical investigations, some general age-related features were found in the clinical pictures of the disorders, the systematics of their course was given, the criteria of expert evaluation derived. The relation of drive disorders to other adolescent psychopathology was stressed. PMID- 2588910 TI - [Changes of membrane polarity of MCF-7 cells in sub-multilayer culture]. AB - Sub-multilayer of MCF-7 cell, an established human breast carcinoma cell line, was achieved by culturing the cells on millipore filters for a long time. The superficial layer cells maintained their membrane polarity features as MCF-7 cells in monolayers did. MAM-6, a human milk fat globule membrane antigen, was polarized distributed in apical domain of 97.5% superficial layer cells revealed by immunoperoxidase cytochemistry. Whereas, among the low layer cells, which had no free surface (apical domain) toward the culture medium and did not show morphological polarity features, only 12.9% expressed surface MAM-6 with weak immunoperoxidase staining and random distribution. But the immunostaining for detecting cytoplasmic MAM-6 in low layer cells was stronger than that in superficial layer cells, indicating that the vectorial delivery and insert of MAM 6 carrying glycoprotein to the plasma membrane seemed to be stopped or declined and became undirectional in the later situation. The study demonstrates that an asymmetric spatial environment, which is composed of a liquid phase space and a solid phase space, is crucial for the establishment of epithelial membrane polarity of MCF-7 cells. PMID- 2588911 TI - [Molecular cloning, gene structure and subcellular distribution of 7s RNA of rat liver cells]. AB - The cDNA copy of in vitro polyadenylated 7s RNA from rat liver cells have been cloned and sequenced. One clone (p 24) contains a 7 s cDNA fragment with 180 bp from 3'end. Sequence analysis indicated that 7s RNA in rat liver cells showed at least one nucleotide substitution compared with that in rat Novikoff hepatoma cells. Southern blot of rat liver and hepatoma genomic DNA shows that 7s RNA gene is a multigene family (10-20 copies per haploid genome) and these loci seems not to be clustered, but have a dispersed array in the genome. We have determined the subcellular distribution of 7 s RNA in rat liver cell by means of RNA-excess hybridization. The result indicated that 42% 7s RNA exists in cell nuclei. Dot hybridization to RNA from liver cells and hepatoma cells proved that the normal liver cells contain relatively more 7 s RNA than that in hepatoma cells. PMID- 2588912 TI - [Morphological study on the role of coated vesicle in the specialization of synaptic membrane in synaptogenesis]. AB - Our object was to characterize the morphological changes of coated vesicles and synaptic membranes during synaptogenesis. Neurons from spinal cords of fetal mice were established as isolated cells in primary culture. After a few days in vitro, the neurons extended their neurites and started their interaction. At timed intervals thereafter, cultures were fixed for electron microscopic observation. Coated vesicles were prominent in the neuronal cytoplasm at the time of synaptogenesis (about 7-10 days in vitro). Similar vesicles were seen in continuity with some cisternae in the Golgi regions and there was an increase in number during the synaptogenic period. Indeed it is not established whether the coated vesicles were exocytotic or pinocytotic in nature, but the cisternae which were in continuity with coated vesicles could be labelled by glucose-6 phosphatase (G6Pase) but not by thiamine pyrophosphatase (TPPase). Such vesicles were also seen in continuity with the neuronal plasmalemma near the closest contact site and contributed their undercoating to pre- and postsynaptic densities. The formation of bilateral membrane specialization was described as being structurally similar to synaptic active zones and appeared to be the first definitive sign of synapseformation. It has been suggested that the synaptic dense material may derive wholly or in part from the exocytic coated vesicles which apparently budding off from endoplasmic reticulum cisternae. This incorporation could provide the mechanism for confining specific characteristics of neuronal membrane to the synaptic region. PMID- 2588913 TI - [Epidermal growth factor receptor of human liver cancer cells and its modulation by phorbol ester]. AB - Using radioligand binding assay, the presence of epidermal growth factor (EGF) receptors in cells of two human liver cancer cell lines, BEL-7402 and SMMC-7721, was demonstrated. The ligand binding data were analyzed by a computer program. The dissociation constants (KD) of the ligand-receptor binding complex at equilibrium for 7402 and 7721 cells were 1.2 nM and 0.8 nM respectively, and their number of EGF receptors per cell were 6.2 x 10(4) and 2.5 x 10(4) respectively. After the treatment of cells with phorbol 12-myristate 13-acetate (PMA), no change either in the affinity or in the number of EGF receptors was found in 7721 cells. However, in the case of 7402 cells, while the number of receptors, like 7721 cells, remained unchanged, the affinity of EGF receptors displayed a time dependent modulation after PMA treatment. It dropped within the first hour to a KD value of 3.0 nM and then gradually returned to the normal control value at 48 hours or even slightly higher than normal (0.95 nM) at 96 hours of treatment. The modulation or down-regulation of EGF receptors by PMA in 7402 cells was paralleled by the simultaneous inhibition of DNA synthesis in these cells as evidenced from their reduction of 3H-TdR uptake. It is not clear what is the basis for the differences found between 7402 cells and 7721 cells in their number of EGF receptors per cell and their responsiveness to PMA treatment. It might be related to their difference in autocrine secretion of alpha transforming growth factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2588914 TI - Cytologic diagnosis by transthoracic fine needle sampling without aspiration. AB - The cytologic findings of transthoracic fine needle sampling without aspiration (fine needle capillary [FNC] sampling) are reported. Eleven patients were examined by FNC sampling while four were examined by the classic fine needle aspiration (FNA) method. In contrast to FNA sampling, FNC sampling produced less patient trauma and admixture of the sample with blood, while giving a better perception of the tumor and its consistency. The quality of the samples obtained by the FNC technique was equal to that of the FNA samples. The results demonstrate that fine needle sampling without aspiration may be used in the study of deep-seated as well as of superficial organs. PMID- 2588916 TI - Changing cytologic detection rates for cervical intraepithelial neoplasia and invasive cancer in a population lacking a mass screening program. AB - The secular trends in the detection rates for cervical intraepithelial neoplasia (CIN) and invasive carcinoma were evaluated for a population lacking a mass screening program. For the period from 1980 through 1987, 185,659 Papanicolaou smears from 176,511 women were examined. The average annual age-adjusted detection rate for invasive cervical cancer declined from 3.7 x 10(-3) in 1980 to 1.4 x 10(-3) in 1987. The rate of cytologic findings consistent with CIN 3 and verified by histology increased from 0.7 x 10(-3) to 2.6 x 10(-3), and the rate of findings consistent with CIN 1 and CIN 2 increased from 4.3 x 10(-3) to 7.2 x 10(-3). The yield of Papanicolaou smear diagnoses consistent with CIN 3 was substantial (more than one case per 1,000) for women up to 60 years old, but was insignificant for older women. PMID- 2588915 TI - National registry of cervical cytologic diagnoses in The Netherlands. AB - The national cervical cytology registry being developed in the Netherlands is described. A large-scale screening program for cervical cancer has been in effect since 1975 in the region of the cities of Nijmegen, Utrecht and Rotterdam. At the start of the pilot projects, laboratories agreed upon a uniform protocol for reporting cytologic findings and recommendations for follow-up examinations in cases of abnormalities. Based on the results of the three pilot projects, in 1985 the Dutch government decided to organize a nationwide screening program for cervical cancer. All pathology laboratories involved in this national screening program are using the same screening protocol and the same coding system for cytologic and histologic diagnoses. By the end of 1989, all pathology laboratories will be linked to a central pathology diagnosis data base (PALGA). Linkage of screening results to previous and follow-up cytologic and histologic findings will enable epidemiologic studies on a regional or national level. Each physician who has submitted specimens will, next to the cytology reports, periodically receive reviews of the number of smears submitted, the cellular composition (quality) of those smears and the follow-up findings. The execution of requests for follow-up examination will be supervised by the participating pathology laboratories. The national cervical cytology registry will enable registration of all relevant cytologic and histologic diagnoses in a uniform way, but will also establish a unique high-quality national data bank, which will be of great value in the analysis of the effectiveness of the national screening program for cervical cancer. It will enable measurement of the impact of various screening protocols and give insight into the behavior of cervical cancer and the progressive or regressive character of its early stages. It will also offer the opportunity to initiate and evaluate quality control protocols. PMID- 2588917 TI - Analysis of five sampling methods for the preparation of cervical smears. AB - The quality of the cervical smear, a decisive factor in the efficacy of population screening, can depend on the sampling method utilized. An analysis was made of the performance of five sample takers in a screening program, each of whom had made approximately 5,000 smears, and of the five sampling methods each had used: spatula alone (method A), Cytobrush plus spatula (method B), Cytopick (method C), cotton swab plus spatula (method D) and Cervex brush (method E). The differences between the sample takers and the sampling methods were significant in both the detection of grade III cervical intraepithelial neoplasia (CIN III) (P less than .01) and in the production of smears containing endocervical cells (EC+) (P less than .018). The data obtained firmly establish the importance of the presence of endocervical cells for smear adequacy. The results of this study indicate that (1) method B (Cytobrush plus spatula) and method C (Cytopick) give superior results in the preparation of EC+ smears and in the detection of CIN III and thus should be used in population screening programs, and (2) methods A and D should not be used for cervical cytologic sampling in such programs. PMID- 2588918 TI - Efficacy of the cytobrush versus the cotton swab in the collection of endocervical cells. AB - Cervical smears should contain endocervical cells to be accepted as adequate for a cytologic diagnosis. Before this study was undertaken, one-third of the smears received in the Cytology Laboratory of Odense University Hospital were inadequate. In an attempt to increase the rate of adequate smears, a randomized study was undertaken to compare the efficacy of the combined spatula-Cytobrush method to that of the spatula-cotton swab method traditionally used by doctors in Denmark. The incidence of smears containing cylindrical and/or metaplastic cells was 89% by the spatula-Cytobrush method as compared to 62% by the spatula-cotton swab method (P less than .001). There were large differences between the rates of adequate smears from the various doctors when using the spatula-cotton swab method (range, 14% to 82%); these differences were far less when using the spatula-Cytobrush method (range, 75% to 100%). A large-scale application of the spatula-Cytobrush method should result in fewer repeat smears required and fewer false-negative smears. PMID- 2588919 TI - Combined use of brushing cytology and endoscopic retrograde pancreatography for the early detection of pancreatic cancer. AB - Seventy-two cases of pancreatic cancer were examined by brushing cytology combined with endoscopic retrograde pancreatography. The results of this combined method were better than those reported for the exfoliative cytologic study of pancreatic fluid. The method detected a minute cancer of the main pancreatic duct that was not detected with any other method. The cells obtained by this technique had very well-preserved cytoplasm and nuclear chromatin, which facilitated making a correct diagnosis. Though this method can be applied only to the main pancreatic duct, it is effective for the diagnosis of ductal cell carcinoma, especially those located at the head of the pancreas, which is the most common site for pancreatic cancer. It is a safe procedure, with no complications seen in this series. The differentiation of carcinoma cells from the benign atypical cells of chronic pancreatitis is illustrated and emphasized. PMID- 2588920 TI - Value of the cytologic analysis of fine needle aspiration biopsy specimens in the diagnosis of pancreatic carcinomas. AB - Between 1982 and 1986, 410 preoperative percutaneous fine needle aspiration (FNA) biopsies of the pancreas were performed on 316 patients clinically suspected of having a malignant pancreatic tumor. Of 58 patients with pancreatic carcinomas subsequently confirmed by histologic investigation, the FNA biopsy yielded a cytologically positive diagnosis of carcinoma in 39 cases (67.2%) and suspicious findings in another 5 cases (8.6%). In 14 cases of malignancy (24.1%), the FNA puncture failed to sample material from the tumor; hence, the cytologic evaluation yielded false-negative results. Of 21 patients with inflammatory disorders of the pancreas, cytologically suspicious cells were observed in 5 cases (23.8%); in none of those 5 cases did the histologic examination show any evidence of carcinoma. This indicates that caution should be taken not to cytologically over-diagnose cases of pancreatitis. On the whole, cytology proved to be a valuable method for the diagnosis of pancreatic carcinoma; it provided the highest rate of positive results in comparison with other modern clinical diagnostic methods. Furthermore, cytology may improve the diagnostic results even in those cases with clinically negative or merely suspicious findings. FNA punctures of the pancreas produced no serious complications in this series. PMID- 2588921 TI - Positive predictive value of fine needle aspiration cytology of breast lesions. AB - The predictive value of fine needle aspiration (FNA) was assessed in 1,181 consecutive cases of breast lesions in which cytologic abnormalities were reported. The positive predictive value (PPV) of an FNA cytologic report of atypia, suspicious or positive was 0.49, 0.95 or 0.996, respectively. In the presence of a suspicious/positive report by both physical examination and mammography, the PPV of a cytologic report of suspicious was 0.99. The PPV was directly correlated with age, partly due to the incidence of fibroadenomas among younger patients; fibroadenomas were present in 53 of 146 cases with a false FNA report of atypia, in 10 of 19 cases with a false FNA report of suspicious and in 2 of 2 cases with a false FNA report of positive. Overall, 93 cases reported as benign by physical examination and mammography were biopsied on the basis of the FNA cytologic report; cancers were diagnosed in 33 of these 93 cases (6 cancers among 42 women less than 40 years old and 27 cancers among 51 women greater than 39 years old). The widespread use of FNA cytology to study breast lesions is thus recommended, without regard to patient age and even in the presence of clinically benign findings, since the increase in the rate of cancer detection is worth the excess of unnecessary biopsies. The predictive value of a positive report of FNA cytology, or even of a suspicious report in the presence of clinical suspicion, is so high that an intraoperative frozen section biopsy might be spared in such cases. PMID- 2588922 TI - Curschmann's spirals and actinomycosis in a fine needle aspirate of the parotid. AB - Fine needle aspiration (FNA) of bilaterally enlarged submandibular salivary glands yielded both Curschmann's spirals and actinomycetes filaments in the FNA smears. Histologic study of specimens from the bilateral submandibulectomy confirmed the actinomycosis but failed to demonstrate the presence of spirals. The presence of Curschmann's spirals in FNA material is a finding not previously described in the English literature. Actinomycosis, although well documented in exfoliative cytology, has been rarely reported in fine needle aspirates. This unique case afforded the opportunity of illustrating the characteristic features of Curschmann's spirals and actinomycetes colonies, as well as reviewing the etiology and pathogenesis of Curschmann's spirals, in FNA material. PMID- 2588923 TI - Survival of patients with malignancy-associated effusions. AB - For a better understanding of the prognosis after the onset of a malignancy associated effusion in patients known or subsequently shown to have cancer, survival time was compared with the findings and the date of the first cytologic diagnosis of an effusion. The number of patients studied was 254; 171 had a pleural and 83 a peritoneal effusion. The average survival time was 25.5 weeks, which was about equal for both sites of effusions. After two years, only 6% of all patients were alive. When the cytologic diagnosis of the effusion was "malignant," only 4% survived after two years; when the cytologic diagnosis was "suspicious for malignancy" and "nonmalignant," these figures were 5% and 7%, respectively. This indicates that a cytologic diagnosis of benign or nonmalignant is not a good indicator of a better prognosis in cancer patients for whom benign causes of the effusion have been excluded. There appeared to be a prognostic relationship between the length of the interval from the initial diagnosis of cancer to the time of examination of the first sample of the effusion: a longer interval was correlated with a better survival. When survival time was viewed in relation to therapy, patients whose pleural effusions were only treated by aspiration were found to have a particularly short average survival (13.9 weeks). PMID- 2588924 TI - Fine needle aspiration cytology of inflammatory pseudotumor of the lung (plasma cell granuloma). Report of four cases. AB - The fine needle aspiration (FNA) cytologic findings in four cases of inflammatory pseudotumor of the lung are described. Histologic material was available for comparison in three of the four cases. FNA of these lesions usually yielded moderately to poorly cellular smears. The smears showed a mixture of chronic inflammatory cells and tissue fragments, without a predominance of plasma cells. Characteristic cytologic findings were not observed. The cytologic findings can be distinguished from those of other circumscribed benign and malignant lesions, however. The diagnosis of an inflammatory pseudotumor of the lung may be suggested by a combination of roentgenographic (a localized density) and FNA findings, which may justify a more conservative surgical approach. PMID- 2588925 TI - Use of monoclonal antibodies to glial fibrillary acidic protein in the cytologic diagnosis of brain tumors. AB - Monoclonal antibodies were used to immunocytochemically demonstrate glial fibrillary acidic protein (GFAP) in 174 smear preparations of brain tumor tissue in order to investigate the presence and distribution of GFAP in a variety of intracranial tumors and to evaluate the value of this technique in the cytodiagnosis of brain tumors. GFAP-positive cells were found in the astrocytic tumors and in some of the oligodendrogliomas, ependymomas and medulloblastomas. In contrast, schwannomas, meningiomas, a primary lymphoma, a hemangiopericytoma pituitary adenomas, germinomas and metastatic tumors were negative for GFAP. The cytodiagnostic accuracy of the 174 brain tumors was raised from 90.8% to 97.1% when GFAP-immunoperoxidase staining was employed to aid the routine cytologic diagnosis. These findings indicate that immunoperoxidase staining for GFAP can be successfully applied to cytologic specimens and is a useful adjunct to routine cytologic diagnosis. PMID- 2588926 TI - Amyloidosis of the liver diagnosed by fine needle aspiration cytology. PMID- 2588928 TI - Fine needle aspiration biopsy of the thyroid using the Chinese brush-holding technique. PMID- 2588927 TI - Nonaspiration fine needle cytology of thyroid tumors. PMID- 2588929 TI - Infarction of thyroid nodule: a rare complication following fine needle aspiration. PMID- 2588930 TI - Cystic thyroid nodules harboring malignancy: a problem in fine needle aspiration cytodiagnosis. PMID- 2588931 TI - Microfilariae in a thyroid aspirate smear: an incidental finding. PMID- 2588932 TI - Cervical tuberculosis coexisting with Trichomonas vaginalis. PMID- 2588934 TI - High and low doses of luteinizing hormone induce different changes in testicular microcirculation. AB - To study the effects of LH on total testicular blood flow and microcirculation, rats were treated with 2.5 or 25 micrograms LH sc and measurements were made on control rats and on LH-treated rats 1, 2, 3, 4, 6 and 12 h, after treatment. After treatment with 25 micrograms LH, total testicular blood flow, as measured with the radioactive microsphere method, was decreased at 6 h and increased at 12 h. Testicular microcirculatory blood flow was recorded with laser Doppler flowmetry and regular oscillations in blood flow, vasomotion, was observed in control rats. Vasomotion was not present 4 and 6 h after treatment with 25 micrograms LH, but returned at 12 h. Prior to and concomitantly with these changes in vasomotion, polymorphonuclear leukocytes accumulated in testicular microvessels and migrated into the interstitial tissue. These changes were followed, 6 h after treatment, by an increased vascular permeability, measured as increased testicular interstitial fluid volume. The lower dose of LH (2.5 micrograms), doubled plasma testosterone concentration and initially decreased interstitial fluid volume, and later induced a slight increase in blood vessel leukocytes. At the times studied, no changes could be observed in the other vascular parameters. In conclusion, it is suggested that LH, probably via some Leydig cell product, promotes regulatory effects on testicular microcirculation, but different magnitudes of LH stimulation induce different responses. PMID- 2588933 TI - Discordant immune and growth response to pituitary and biosynthetic growth hormone in siblings with isolated growth hormone deficiency type IA. AB - Two brothers with familial isolated growth hormone deficiency type IA homozygous for the same 6.7 kb deletion on chromosome 17 including the growth hormone gene were intermittently treated with various forms of hGH for more than 7 years. While the elder brother (Patient 1) showed a good growth response to pituitary hGH, the younger one (Patient 2) developed high titre growth blocking hGH antibodies early in the course of treatment and grew only 2.2-3.9 cm/year on a hGH dose of 12-26 IU/m2 per week. When the younger brother was changed to a higher dose (33 IU/m2 per week) of biosynthetic methionyl hGH he had striking catch-up growth and he has subsequently maintained a height velocity of 10.0 cm/year for the last 2 years. During this time his antibody titres have decreased over 1000-fold. These findings demonstrate that therapy with biosynthetic methionyl hGH may provide an effective form of treatment for subjects with isolated growth hormone deficiency type IA who do not grow in response to native hGH, and imply that biosynthetic methionyl hGH may be less antigenic than pituitary derived hGH. PMID- 2588935 TI - The role of insulin-like growth factor I in growth of diabetic rats. AB - Insulin-deficient, streptozotocin-diabetic rats show severe metabolic disturbances and stop growing. Besides insulin, these animals also lack growth hormone and insulin-like growth factor-I. We examined whether or not growth parameters correlate with IGF-I serum levels in young rats with streptozotocin diabetes of different severity. In the diabetic rats, blood glucose varied between 18.4 and 38.6 mmol/l (healthy controls between 6.1 and 9.3), IGF-I serum levels between 2.6 and 15.6 nmol/l (controls between 19.6 and 26.5), and serum insulin levels between 0.05 and 0.14 nmol/l (controls between 0.36 and 0.55). We found a highly significant linear correlation between IGF-I serum levels and the two investigated growth parameters, tibial epiphyseal width and longitudinal tibial bone growth. The finding that these indices of growth are strongly correlated with IGF-I serum levels in young rats with diabetes of different severity, suggests that IGF-I is a major determinant of growth. This is in keeping with our earlier demonstration that exogenously infused IGF-I promotes growth in diabetic rats. PMID- 2588936 TI - Pharmacokinetics of 3,5,3'-triiodothyroacetic acid and its effects on serum TSH levels. AB - 3,5,3'-triiodothyroacetic acid is an effective inhibitor of TSH secretion in central hyperthyroidism. Serum, 3,5,3'-triiodothyroacetic acid was measured with an RIA preceded by immunoprecipitation. An anti-3,5,3'-triiodothyroacetic acid antibody was obtained in rabbits, using 3,5,3'-triiodothyroacetic acid coupled to hemocyanin and diazotized benzidine as antigen (cross-reactivity with T4, T3, tetraiodothyroacetic acid was 0.2, 1.1, and 5%, respectively). Endogenous 3,5,3' triiodothyroacetic acid levels could not be detected in 14 euthyroid, 10 hypothyroid and 10 hyperthyroid sera (detection limit 0.055 nmol/l). Kinetic studies were performed in 6 healthy male subjects who received an oral and an iv dose of 1050 micrograms of 3,5,3'-triiodothyroacetic acid. The serum measurements were analysed according to a non-compartmental method. The half-life of 3,5,3' triiodothyroacetic acid was 6 h 22 min +/- 29 min, the volume of distribution was 114 +/- 9 1/70 kg, and the plasma clearance rate was 298 +/- 141.(70 kg)-1.day-1. Highest 3,5,3'-triiodothyroacetic acid levels were measured after 40 min (for T3 2-3 h) and its absorption was 67 +/- 6%. The nadir of the mean TSH levels was 0.72 +/- 0.09 mU/l 6 h after 3,5,3'-triiodothyroacetic acid administration. However, the time course of serum TSH response did not differ from that obtained after administration of 37.5 micrograms T3. The dose-response effect for TSH was studied using oral doses of 350, 700, 1400 and 2800 micrograms 3,5,3' triiodothyroacetic acid. TSH was measured 9 h after 3,5,3'-triiodothyroacetic acid administration at 17.00 h, and compared with control serum TSH levels obtained at 08.00 h (1.53 +/- 0.11) and at 17.00 h the day before the test (1.87 +/- 0.11). They were 1.05 +/- 0.15 (N = 9, mean +/- SEM), 0.83 +/- 0.08 (N = 24), 0.66 +/- 0.06 (N = 24), and 0.43 +/- 0.02 mU/l (N = 6), respectively. In conclusion, TSH inhibition by 3,5,3'-triiodothyroacetic acid is similar to T3, with a potency ratio of 1 to 18. PMID- 2588937 TI - Lys- and Tyr-arylamidase activities in serum and brain during the estrous cycle of the rat. AB - Peptidase enzymes are involved in neuropeptide processing or degradation. In order to analyse a possible functional participation of these enzymes, arylamidase activity of several rat brain regions and serum was assayed in the soluble fraction during the estrous cycle using L-Lys- and L-Tyr-beta naphthylamide as substrates. Significant differences were present in the hypothalamus, the pituitary and serum when both substrates were used. However, there were no differences in cortical areas. These results suggest a role for arylamidase activity in the hormonal changes that happen during the estrous cycle of the rat. PMID- 2588938 TI - Diurnal variation in TSH and free thyroid hormones in patients on thyroxine replacement. AB - Eleven patients with treated hypothyroidism were investigated to examine the effects of time on their thyroid function tests. Each patient was clinically and biochemically euthyroid on once daily thyroxine replacement therapy, taken in the morning. TSH followed a diurnal rhythm with a peak level at 23.30 h and a trough level at 14.30 h. Four subjects had TSH trough levels within the normal range, but with peak levels outside this range. FT4 and FT3 levels fell from their highest levels some three hours after ingestion to the lowest levels just prior to the next dose. This study shows that there are significant time-related variabilities in TSH and thyroid hormone levels in treated hypothyroid patients. This should be taken into account when interpreting results of their thyroid function tests. PMID- 2588939 TI - Role of testosterone in regulating the growth of mice from lines selected for low vs high plasma insulin-like growth factor-I concentrations. AB - A study was undertaken to investigate the role of testosterone in regulating growth and circulating levels of insulin-like growth factor-I in male mice from lines divergently selected on the basis of plasma IGF-I. Controls of each lines were sham-operated at 10 days of age and treated with peanut oil from day 14 to day 70. A second group, which was castrated at 10 days and treated with testosterone enanthate (0.5 micrograms.(g body weight)-1.day-1) from day 14 to 70, did not differ from controls in body weight but had higher plasma IGF-I concentrations. Delaying testosterone therapy until day 42 in a third group retarded growth, with body weights being significantly lower than those of other two groups from days 35 to 56. However, plasma IGF-I levels in this group were not different from those of controls. Effects of line and treatment were additive. It is concluded that the greater pubertal growth of high-line compared to low-line males is not due to greater stimulation of circulating IGF-I by testosterone. Furthermore, testosterone does not appear to influence pubertal growth by acting on circulating levels of IGF-I. PMID- 2588941 TI - Changes of serum thyroid hormone levels induce malformations on early embryogenesis in rats. AB - The incidence of malformation is increased in infants of hyperthyroid or hypothyroid woman. Although many papers reported that the fetus is insulted from maternal thyroid hormone, the placenta (maternal-fetal barrier) is not yet fully developed before 11.5 days of gestation in rat embryos, suggesting the effect of thyroid hormone on early rat embryogenesis. This study was, therefore, undertaken to investigate whether excess or lack of thyroid hormones would affect early embryogenesis in rat embryo culture. Malformations including open neuropore and microencephaly were observed in 10 of 30 embryos incubated in hyperthyroid serum, and in 12 of 42 cultured in T3-enriched normal serum. Similar malformations were observed on 14 of 42 embryos cultured in hypothyroid serum and in 10 of 30 cultured in hypothyroid serum supplemented with T3. The frequencies of these malformations were significantly higher than in the control embryos (0 in 72 embryos) cultured with normal rat serum. These results suggest that the maternal thyroid status might play an important role for the complication of fetal malformations during early gestational period. PMID- 2588940 TI - The respective effects of serum thyroxine and triiodothyronine on serum thyrotropin and lipid parameters in endemic juvenile hypothyroidism. AB - The respective effects of serum total T4 concentration and of serum total T3 concentration on serum TSH concentration and on lipid parameters were compared in 84 7- to 16-year-old children of the Northern Zaire goitre endemia classified in group A (T4 greater than 77 nmol/l and T3 greater than 1.69 nmol/l), B (low T4, normal T3) and C (low T4, low T3). Mean serum TSH level was normal in group A (2.3 mU/l), it raised to 39.4 mU/l in group B (p less than 0.001) and to 166.3 mU/l in group C (p less than 0.001 vs A and B). Low density lipoprotein cholesterol and apoprotein B were increased in group B vs A (p less than 0.05) and in group C vs A (p less than 0.001) and B (p less than 0.001 for apoprotein B; not significant for cholesterol). High density lipoprotein cholesterol and apoprotein A1 were similar in the three groups. Mean serum triglyceride level, not different in groups A and B, was doubled in group C (p less than 0.001). Multiple regression analysis showed that serum TSH, apoprotein B, and triglyceride levels were influenced by both thyroid hormones concentrations with a predominant effect of serum T4 on the first two parameters and of serum T3 on the last one. In conclusion, low serum T4 with normal T3 concentrations resulted in an increase in serum TSH and in an altered lipid metabolism; it clearly represented an hypothyroid state. PMID- 2588942 TI - [Cystine transport and glutathione metabolism in human erythrocytes]. AB - Cystine was transported into human erythrocytes in the presence of tertiary-butyl hydroperoxide (t-BH) or 1-chloro-2, 4-dinitrobenzene (CDNB). The transport rate of cystine was dependent on the extracellular concentration of t-BH or CDNB, and on the incubation time. By Dowex-1 column chromatography, the transported cystine was incorporated into fractions of glutathione disulfide (GSSG) and glutathione-S (GSH-S) conjugate. Cystine was also transported into reconstituted erythrocyte ghost with GSSG. The transport of cystine was Na+ dependent and decreased in the presence of N-ethylmaleimide, and it was competitively inhibited by DL homocystine and L-alanine. The inhibition rates by DL-homocystine and L-alanine were 75% and 68%, with similar Ki values of 0.7 mM and 0.6 mM, respectively. The Km value for cystine transport was 0.15 mM. The activity of GSH-cystine transhydrogenase was detected in the hemolysate and this enzyme is thought to catalyze the action of incorporation of cystine into GSH. This enzyme was partially purified from normal human erythrocytes. In the presence of CDNB, similar rates of cystine transport were observed among the diabetic patients (n = 11), hypoxemic patients (n = 10) and the control subjects (n = 20). It is suggested that cystine transport is induced for glutathione synthesis when human erythrocytes are exposed to oxidative stresses. PMID- 2588943 TI - [Burst promoting activity of lymphocytes from uremic patients]. AB - PHA-leukocytes conditioned medium (PHA-LCM) prepared from the patients with chronic renal failure and normal control was tested for BPA by progenitor cell assay with methylcellulose culture method. The BPA of uremic patients, expressed as a percentage of standard CM, was significantly lower than that of normal subjects (96 +/- 9%). However, there was no correlation between BPA and the severity of anemia. The number of circulating BFU-E per milliliter of blood was significantly lower in uremic patients (71 +/- 77) than in normal controls (131 +/- 96), and the number correlated with the severity of anemia. From these results, the maturation process of erythroid series in uremic patients appeared to be impaired at a stage between pluripotent stem cell and BFU-E, and might be secondary to inefficient production of BPA by lymphocytes. PMID- 2588944 TI - [Neutrophil-associated IgG and neutrophil-binding IgG in autoimmune neutropenia]. AB - Neutrophil-associated IgG (NAIgG) and neutrophil-binding IgG in sara (NBIgG) of 77 patients with neutropenia suspected to be caused by autoimmune mechanisms (group A) and 31 patients with aplastic anemia or myelodysplastic syndrome (group B) were assayed by flow cytometry. Auto-NBIgG was elevated in 32% of the patients in group A, particularly in about 70% of those with collagen diseases or ITP, but the level was normal in group B. Elevated NAIgG with normal auto-NBIgG levels was found in 27% of the patients in group A and in 64% of the patients in group B. The assay of auto-NBIgG was useful for detection of anti-neutrophil autoantibodies and for the diagnosis of autoimmune neutropenia. In addition, the level of NAIgG may be non-specifically elevated in non-immune neutropenia. PMID- 2588945 TI - [Spontaneous remission of four months' duration in hypoplastic leukemia with tetraploid chromosome after blood transfusions and infection]. AB - Spontaneous complete remission of four months' duration was observed in a 51-year old male with hypoplastic leukemia. Cytogenetical analysis revealed that leukemia cells of this patient were tetraploid. The diameter of leukemia cells involving myeloid cells ranged from 30 to 50 mu. The remission was apparently associated with repeated blood transfusions and severe infection. Complete remission was confirmed by normal morphology and karyotype of the bone marrow cells, although in vitro marrow stem cell growth did not return to normal. Thus, normal hematopoiesis may not have recovered when the diagnosis of spontaneous remission was made. PMID- 2588946 TI - [HTLV-I carriers in ATL/L-nonendemic area--with reference to blood transfusions]. AB - Sera from 5,705 persons were tested for antibodies to human T-cell leukemia virus type 1 (HTLV-I) by gelatin particle agglutination test (PA) and enzyme immunoassay (EIA) as screening methods, and the antibodies were confirmed by indirect immunofluorescence assay (IF) and Western blotting method (WB). The antibodies were detected in 30 (1.34%) of 2,239 patients who had received blood transfusions, 3 (0.29%) of 1,022 healthy blood donors, all 18 adult T-cell leukemia/lymphoma (ATL/L) patients, 23 (47%) of 49 family members of the ATL/L patients and 10 (0.53%) of the other 1,898 persons. Before the introduction of the mass screening of healthy blood donors by the Japan Red Cross Blood Center, 17 (2.29%) of 743 recipients tested were positive for the antibodies by PA and most of them were confirmed by IF and WB. Ten of these 17 recipients tested were negative for the antibodies before the blood transfusions. After the introduction of mass screening, 13 (0.87%) of 1,496 recipients tested were positive for the antibodies by PA, but the seroconversion of the antibodies by blood transfusions could not be confirmed clearly. In persons with low titers (1:16-1:64) in PA, the coincident rate of positive reaction with EIA, IF and WB was only 9.5%, 0.0% and 23.8%, respectively, and most of the immunoglobulin (Ig) class was IgM. On the other hand, in those with titers of 1:128 or greater in PA, the coincident rate was 72.7%, 81.8% and 90.9%, respectively, and the Ig class was IgG or IgG + IgM. PMID- 2588947 TI - [Immunochemical characterization of platelet-specific alloantigen Baka]. AB - We investigated the location of platelet-specific alloantigen Baka on platelet membrane glycoproteins. In indirect immunoprecipitation experiments, the anti Baka antibody precipitated glycoprotein (GP) II b and a small amount of GP III a. The immunoblots using partially purified GP II b/III a complex as the target antigen indicated that GP II b alpha carried the Baka alloantigen. When the partially purified GP II b/III a complex digested with chymotrypsin was examined, the Baka alloantigen was found on a 65 kD fragment derived from GP II b alpha under reducing conditions. In addition, the immunoblots after two-dimensional nonreduced-reduced SDS-PAGE directly indicated that the 65 kD fragment had a mol. wt. of 80 kD under nonreducing conditions. The immunoblots using platelets digested in situ with chymotrypsin indicated that the 65 kD fragment of GP II b alpha was retained by the platelet membrane. We conclude, therefore, that the Baka alloantigen is located on a 65 kD fragment that represents the membrane side of the cleavage site of chymotrypsin on GP II b alpha. PMID- 2588948 TI - [Analysis of platelet surface conformation in thrombin-induced aggregation]. AB - We used flow cytometry to investigate the change of platelet membrane glycoproteins (GPIb and GP IIb/IIIa) and the distributions of fibrinogen (Fbg), thrombospondin (TSP) and fibronectin (Fn) on the surface of thrombin-stimulated platelets. The binding of a monoclonal antibody directed at the von Willebrand factor binding site on GPIb decreased in thrombin-stimulated platelets. This antibody caused a reactive delay in thrombin-induced aggregation, but had little influence on aggregability. Slight thrombin-induced aggregation was observed even after blocking the binding of Fbg to GP II b/IIIa. The new expression of GP II b/IIIa was detected on the surface of thrombin-stimulated platelets, whereas there was little increase of Fbg dependent on this GP II b/IIIa. An increase of TSP after thrombin stimulation was observed on the surface of platelets of healthy controls and patients with Glanzmann's thrombasthenia (Type I). The level of on platelet surface was slightly increased by thrombin stimulation. The mechanism involved in thrombin-induced aggregation appears to differ from that in ADP-induced aggregation. PMID- 2588949 TI - [Mechanisms of human platelet aggregation and release reaction induced by influenza virus]. AB - Mechanisms of aggregation and release reactions of human platelets induced by non hemolytic influenza virus were studied. The influenza virus (PR/8 strain) caused aggregation of platelets with ATP release in a dose-dependent manner over the range of 640-10,240 HA titers. The aggregation was always preceded by a lag period and subsequent shape changes. The virus-induced aggregation was enhanced by exposure of the reaction mixtures to cold at 4 degrees C for 30 min and inhibited by apyrase, acetylsalicylic acid and dipyridamole. Ingestion of acetylsalicylic acid also inhibited the aggregation. Gel-filtered platelets were aggregated by influenza virus only after the reaction mixtures had been previously incubated at 4 degrees C for 30 min and then stirred at 37 degrees C. In the absence of divalent cations (Ca2+ less than or equal to 2 x 10(-5) M, Mg2+ less than or equal to 1 x 10(-5) M), gel-filtered platelets were not aggregated by influenza virus. These results suggest that influenza virus was absorbed onto the platelet surface and caused the release of ADP from platelets, which in turn, aggregated platelets. PMID- 2588950 TI - Heterogeneous features of Ph-negative CML--possible existence of Ph-negative, bcr rearrangement-negative CML. AB - We have examined eight patients with Ph-negative chronic myelocytic leukemia (CML). Two of the patients had the same molecular abnormalities as well as the same clinical and hematological features as those of Ph-positive CML. The other six patients showed no genomic rearrangement. This group was hematologically divided into four subgroups, namely chronic myelomonocytic leukemia, undifferentiated chronic myeloproliferative disorder, chronic neutrophilic leukemia and CML-like syndrome. This last subgroup resembled Ph-positive CML in many points except for rather moderate proliferation of granulocyte lineage, and it was difficult to clinically separate it from Ph-positive CML. PMID- 2588951 TI - Clinical and cytogenetic features in six patients with chronic myelogenous leukemia and a complex Philadelphia translocation. AB - Six patients with chronic myelogenous leukemia and a complex Philadelphia (Ph1) translocation are described. The complex Ph1 translocations were a three-way translocation in five patients and a five-way translocation in one. Additional chromosomal aberrations were detected in four of five patients when the blastic crisis supervened. The median survival time was 42 months. The remaining patient died of acute myocardial infarction 23.5 months after the diagnosis of CML was made. There seems no difference between these six patients and those with the standard Ph1 with respect to clinical, hematologic and cytogenetic findings. PMID- 2588952 TI - Cytogenetic evidence for a clonal disorder involving CFU-GEMM, BFU-E and CFU-C in patients with myeloproliferative disorders. AB - We grew multilineage hemopoietic colonies in vitro from 4 patients with myeloproliferative disorders (MPD) having chromosomal aberration, and performed cytogenetic analysis of single CFU-GEMM, BFU-E and CFU-C-derived colonies on Day 14 of culture. In Patient 1 with acute myelofibrosis, CFU-GEMM and BFU-E colonies had only a 47, XX, +C karyotype. In Patient 2 with polycythemia vera, CFU-GEMM, BFU-E and CFU-C colonies all showed the same abnormal karyotype of 46, XY, -12, +der(12)t(1;12). Patients 3 and 4 had primary myelofibrosis, and their respective karyotypes were 46, XY, 13q- and 46, XX, -6, +der(6)t(1;6) in CFU-GEMM, BFU-E and CFU-C colonies. In these 4 patients, the karyotype of bone marrow or circulating mononuclear cells was identical to that of hemopoietic colonies. These results indicate a clonal origin of MPD at the level of CFU-GEMM. PMID- 2588953 TI - Transfer of the adenosine deaminase (ADA) gene of a B-lymphoblastoid cell line (LCL) to an ADA-deficient LCL by a microcell-mediated chromosome transfer technique. AB - As a model of somatic cell gene therapy, a normal adenosine deaminase (ADA) gene was introduced into a B-lymphoblastoid cell line (LCL) established from a patient with ADA deficiency by microcell-mediated chromosome transfer (MMCT). A LCL derived from his mother was used as a gene donor. Seven fusion experiments were performed and hybrid cells were pipetted into 123 wells. After selection in the presence of deoxyadenosine, cells grew in 12 wells at Week 9 after fusion. Among these wells, ADA activity of hybrids was low in 4 wells, 130-280% of that of the donor LCL in 7 wells and very high in one well. Hybrid cells in 4 wells with ADA positive cells were investigated for the time-course of expression of ADA activity. In one well, ADA activity was expressed until Week 36, while, in 3 wells, ADA activity decreased or was lost between 21-36 weeks after fusion. These findings indicate the transfer of chromosome 20 containing a normal ADA gene into recipient cells and the deletion of this chromosome from some part of the hybrid cells. Karyotyping at Week 35 or 37 revealed 47 chromosomes in about 30% of the cells in 2 wells, which suggests that these hybrids were relatively stable in culture. PMID- 2588955 TI - Fatal graft-versus-host disease following transfusion during open heart surgery. AB - We report fatal transfusion-associated graft-versus-host disease (GVHD) in a patient who was not severely immunosuppressed. A 58-year-old man received 800 ml of fresh whole blood from his son and an unrelated volunteer donor during open heart surgery. On the 10th day after the operation, he suddenly had a high fever, followed by generalized skin rash and liver dysfunction. Pancytopenia due to bone marrow aplasia developed a week later. A skin biopsy revealed a cutaneous lesion highly compatible with acute GVHD. The patient did not respond to high-dose methylprednisolone therapy, and died of multiple organ failure on the 18th day after the operation. PMID- 2588954 TI - A case of immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma with unusual clinical manifestations. AB - A 67-year-old male consulted an otolaryngologist with a complaint of dysphagia due to a large polypoid mass in the hypopharynx. A biopsy of the mass revealed immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma of helper/inducer subset occurring in lymphoid tissues of the hypopharynx. Although general lymphadenopathy was not seen, further biopsy of an inguinal lymph node showed small foci of lymphoma cells, suggesting the generalized distribution of this malignancy. To our knowledge, this is the first report of this malignancy mimicking primary pharyngeal sarcoma. PMID- 2588956 TI - Systemic lupus erythematosus in a patient with refractory anemia. AB - A 69-year-old man was diagnosed as having refractory anemia (RA), accompanied by pancytopenia of two years' duration, myelodysplasia in all three cell lines, abnormal karyotype of 46, XY, 20q--in bone marrow cells, and positive antinuclear and DNA antibody tests. One year after his first visit, he developed arthritis and maculopapular erythematous rashes. The histologic features of the skin lesions were similar to those of in discoid lupus erythematosus. He was diagnosed as having systemic lupus erythematosus supervening refractory anemia. PMID- 2588957 TI - Effect of vitamin K deficiency on urinary gamma-carboxyglutamic acid excretion in rats. AB - Since gamma-carboxyglutamic acid (Gla) in Gla-containing proteins is stoichiometrically excreted into urine as free Gla, urinary Gla excretion is believed to reflect the rate of synthesis and degradation of vitamin K-dependent proteins and the utilization of vitamin K in body. We studied the daily changes in urinary Gla excretion and plasma vitamin K-dependent clotting factor levels in rats fed vitamin K-deficient diets followed by subcutaneous injection of vitamin K1 or after the oral administration of Warfarin. Urinary Gla excretion in normal rats fed a standard diet that contained about 500 ng of vitamin K1 per gram of diet was 2.35 +/- 0.25 mumoles/day, but the level in rats fed a markedly vitamin K-deficient diet (less than 5 ng/g) decreased to 1.40 +/- 0.14 mumoles/day. When rats were fed a moderately vitamin K-deficient diet (20-50 ng/g), plasma vitamin K-dependent clotting factor levels decreased significantly, but urinary Gla excretion did not decrease. Warfarin, a vitamin K antagonist, caused a significant decrease in urinary Gla excretion and plasma clotting factor levels. When vitamin K, (200 micrograms/kg) was injected subcutaneously in rats fed a markedly vitamin K-deficient diet, the plasma vitamin K-dependent clotting factor levels recovered quickly to normal, but urinary Gla excretion showed only a partial recovery to 1.74 +/- 0.15 mumoles/day. These results indicate that urinary Gla excretion decreases in vitamin K deficiency, but changes in urinary Gla excretion do not reflect vitamin K deficiency in rats as sensitively as changes in the prothrombin time and plasma K-dependent clotting factor levels. PMID- 2588958 TI - Glanzmann's thrombasthenia associated with a transient deficiency of factor XIII. AB - A three-year-old girl suffering from ecchymoses developed severe epistaxis. The diagnosis of thrombasthenia was made on the basis of platelet aggregation studies, flow cytometric analysis with monoclonal antibodies and gel electrophoretic analysis. In addition, coagulation studies at the time of epistaxis repeatedly showed a transient deficiency of factor XIII activity and antigen. PMID- 2588959 TI - Fibrinogen Sapporo: dysfibrinogenemia characterized by the replacement of A alpha arginine-16 by histidine resulting in the delayed release of fibrinopeptide A by thrombin. AB - Congenital dysfibrinogenemia was found in a 60-year-old asymptomatic female and her daughter. Purified fibrinogen derived from the propositus, apparently a heterozygote for the abnormality, characteristically showed delayed but complete release of fibrinopeptide A upon digestion with thrombin but its defective release by Ancrod, a snake venom enzyme, from half of her fibrinogen molecules. This congenital dysfibrinogenemia with an A alpha arginine (Arg) to histidine (His) substitution was tentatively designated as fibrinogen Sapporo. Although this type of abnormal fibrinogen had been identified among Caucasians, no such cases have so far been reported in Japan. PMID- 2588960 TI - Plasma levels of von Willebrand factor and plasminogen activator in patients with arterial thromboembolism--with special reference to their correlation to the increased catabolism of both fibrinogen and platelets. AB - Plasma levels of von Willebrand factor(vWF) and plasminogen activator(PA) in the plasma of venous blood before and after 5 minutes' venous occlusion were studied in 104 patients with various types of arterial thromboembolic disease and 30 age matched healthy subjects. Levels of beta-thromboglobulin(beta-TG) were determined in plasma prior to the venous occlusion. In 29 patients and 7 control subjects, turnover of intravenously injected 125I-labeled fibrinogen was studied. Mean plasma levels of von Willebrand factor antigen(vWF: Ag) and ristocetin cofactor activity(vWF: RCo) were significantly higher in patients than in controls both before and after the venous occlusion. Mean plasma PA activity was significantly lower in patients than in controls both before and after the venous occlusion, but mean plasma PA antigen before the venous occlusion was significantly higher in patients than in controls. Plasma clearance of i.v. injected 125I-labeled fibrinogen was significantly accelerated, and the catabolic flux(j3x) of fibrinogen calculated according to a two-compartment model was significantly higher in patients than in controls. Significant relationships were observed between T1/2 of 125I-labeled fibrinogen and the following: plasma levels of vWF: Ag both before and after the venous occlusion, PA activities after the occlusion, PA antigen before the occlusion, and the net decrease in PA activities and the net increase in PA antigen as a result of the occlusion. Significant relationships were also observed between j3x of fibrinogen and the following: plasma levels of vWF: Ag both before and after the venous occlusion, vWF: RCo after the occlusion, PA activities after the occlusion, PA antigen before the occlusion, and the net decrease in PA activities resulting from the occlusion. Plasma levels of beta-TG, which were significantly higher in patients than in controls, were not correlated to plasma levels of vWF and PA or to parameters of fibrinogen turnover. These results suggest that the change in endothelial cell function is responsible for the abnormal plasma levels of both vWF and PA and for the acceleration of fibrinogen metabolism in patients with thromboembolic disease. PMID- 2588961 TI - Hemoglobin Hope found in a patient with basal cell carcinoma of the genial region. AB - Hemoglobinopathy was detected in a 72-year-old female with basal cell carcinoma of the genial region during high-performance liquid chromatography of hemolysate for the assay of HbA1c. Structural analysis demonstrated that this abnormal hemoglobin was identical to Hb Hope [beta 136(H14)Gly----Asp]. No clinical or hematological abnormality was observed. A study of the family revealed that a younger sister and two sons of the propositus had the same hemoglobin variant. This is the second observation of Hb Hope in a Japanese family. PMID- 2588962 TI - UV-induced DNA repair in leukemic cell differentiation. AB - Ultraviolet light (UV)-induced DNA repair during myeloid leukemic cell differentiation was examined. Human myeloid leukemic cells could be induced to differentiate in vitro into mature cells by various chemical inducers that lost their proliferating potencies. In spite of decrease of proliferation capacity, almost all these terminally differentiated myeloid leukemic cells invariably showed UV-induced unscheduled DNA synthesis (UDS) at low energy of UV irradiation (3-5J/m2). This indicated that the terminally differentiated myeloid leukemic cells are functionally quite different from mature granulocytes in chronic myeloid leukemia (CML) or in normal peripheral blood. In HL-60 cells, UV-survival was enhanced in the process of differentiation induced by 1.25% DMSO or 0.6 mM sodium n-butyrate. The degree of enhancement of UV-survival was correlated with the increased amount of UDS. The process of myeloid leukemic cell differentiation which is completed without loss of capacity performing repair DNA synthesis was one of the characteristics of the terminally differentiated myeloid leukemic cells induced by chemical inducers in vitro and this function may support the hypothesis that DNA breaking and rejoining are involved in a mechanism of cytodifferentiation. PMID- 2588963 TI - 1 alpha, 25-dihydroxyvitamin D3 enhances the up-regulation of interleukin-2 receptor (p55) by interleukin-2. AB - The effect of 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25(OH)2D3) on the expression of interleukin-2 (IL-2) receptor in activated T lymphocytes was examined. 1 alpha, 25(OH)2D3 enhanced the expression of IL-2 receptor (p55, Tac peptide) in phytohemagglutinin (PHA)-stimulated (3 days) human peripheral blood mononuclear cells (PBM) only in the presence of IL-2 without affecting the proliferation of the cells. This enhancement was dependent on the concentration of both IL-2 (0-1 U/ml) and 1 alpha, 25(OH)2D3(0-10(-7)M). The addition of interleukin-1 (IL-1, 0-100 U/ml), did not enhance the expression of IL-2 receptor in these cells in the presence of IL-2. Moreover, 1 alpha, 25(OH)2D3 had the same effect on two cell lines, Kit225 (an IL-2 dependent cell line established from a patient with T cell chronic lymphocytic leukemia) and YT (an IL-2 independent natural killer (NK)-like cell line from a patient with acute lymphocytic leukemia). Thus, 1 alpha, 25(OH)2D3 enhances the up-regulation of IL-2 receptor (p55) by IL-2 not only in activated T cells but also in the NK-like cell line. PMID- 2588964 TI - Choosing a career in psychiatric-mental nursing: do more clinical placements in this area for undergraduate student nurses make a difference? (Part One). AB - The purpose of this article is to address the broader issue of how to increase the interest among undergraduate student nurses in choosing a career in the psychiatric-mental nursing field upon graduation. A description is given of the new clinical placement option that was offered in Psychiatric-Mental Health Nursing in April-May 1989 for the 100 hours of clinical experience (Nursing 439 Intersession) for undergraduate nursing students completing their third year of their Bachelor of Nursing degree at the Faculty of Nursing, University of Calgary. One of these settings was an acute care psychiatric unit (McNab Mental Health Centre) and the other a provincial psychiatric hospital (Alberta Hospital Ponoka). This article is divided into three parts: 1) An overview of the present psychiatric-mental nursing content of the undergraduate program of U. of C.'s Faculty of Nursing; 2a) The perceptions of the four students who chose to do their Intersession-1989 clinical experience in a long-term care psychiatric setting; 2b) the perceptions of the preceptors who worked with the students in that long-term care setting; 3) and concluding comments about this relatively new venture, including some of the implications for future planning and research in terms of the issues pertaining to clinical placements, and recruitment of baccalaureate-prepared nurses for the psychiatric-mental health field. PMID- 2588965 TI - Income tax credit and continuing nursing education. PMID- 2588966 TI - Pain control in labor: the obstetrical use of TNS. PMID- 2588967 TI - Hospitals striving to improve nursing environment. PMID- 2588968 TI - You did not have to be a NICU nurse. PMID- 2588969 TI - Nursing research: flourishing at the Cross Cancer Institute. PMID- 2588970 TI - Research for practice: an AFNR update. PMID- 2588971 TI - The "OPN" virus and five fingers will do it. PMID- 2588972 TI - Relationship between local brain glucose metabolism and maze patrolling in adult and aged rats. AB - Rats in the tunnel maze are not rewarded or punished. The active information gathering of the rats in this apparatus is supposed to be guided by learning and memory processes. As assessed by the 2-deoxyglucose method the age-related behavioral changes in rats in this maze are partly reflected in functional metabolic changes in cortical and hippocampal structures. PMID- 2588973 TI - Analysis of simple GSR measures: differential diagnostic GSR signs in hypertonics, neurological patients and healthy controls. AB - A statistical analysis of GSR measures in three groups of Ss (Hypertonics-HP, Neurological patients-NP, and Controls-CG), subjected to standard electrodermal stimulation supports the existence of a differentiated inner connection among various GSR measures in the three groups. Latency in the CG was found negatively to correlate with amplitude of the derivational curve, while in the other two groups it proved to be an independent measure. It is assumed that the temporal GSR measures reflect its dynamic properties, while amplitude is an indicator of the overall level of the sympathetic nervous system and of the magnitude of changes in the membrane potentials of sweat glands. A point is also made of certain diagnostic applications for differentiating disorders due to organic causes from functional ones, within the framework of man's psychophysiological unit. PMID- 2588974 TI - The changing psychosocial profile of patients before and after coronary artery bypass surgery: a preliminary report with the enlarged Bortner-scale. PMID- 2588975 TI - A comparative study on pattern reversal visual evoked responses in school children and in adults. PMID- 2588977 TI - The development of motor behaviour during feeding. PMID- 2588976 TI - Respiratory patterns during sleep states in preterm infants. PMID- 2588978 TI - Perinatal risk factors and minor neurological dysfunction. PMID- 2588979 TI - Relations between psychological and neurological signs of minimal brain dysfunction in children. PMID- 2588980 TI - Determinants of threat-induced behaviour in the rat. PMID- 2588981 TI - Some relations between successfulness of biological feedback and psychological variables. PMID- 2588982 TI - Pain threshold in patients with atopic eczema influenced by hypnosis. PMID- 2588983 TI - Changes in the optokinetic nystagmus cessation limit under the influence of ethanol and caffeine. PMID- 2588984 TI - Effects of the synthetic analogue of vasopressin (DGAVP) at systemic and local application on the behaviour of the laboratory rat. PMID- 2588985 TI - Behavioural teratogenic risk of perinatal administration of dexamethasone in combinations with phenoterol. PMID- 2588986 TI - The changes of peroxidation of unsaturated fatty acids in epileptic mirror focus in rats. PMID- 2588987 TI - Evaluation of the effects of noise exposure on various body functions in low birthweight newborns. PMID- 2588988 TI - Noradrenergic alterations in the brain stem of adult rats after a model perinatal insult. PMID- 2588989 TI - Myocardial infarction in older age: impact on the decision to retire from active service. PMID- 2588990 TI - Specific behaviour as an objective indicator of emotional arousal in man. PMID- 2588991 TI - Potentiation of the anticonvulsant action of clonazepam by phenytoin could be demonstrated in adult as well as young rats. PMID- 2588992 TI - Effect of carbamazepine on cortical interhemispheric responses in adult and young rats. PMID- 2588993 TI - True shunt in relation to venous admixture in an experimental porcine model of early ARDS. AB - Using the multiple inert gas elimination technique, ventilation/perfusion (V/Q) relationships were studied in an experimental porcine model of the early Adult Respiratory Distress Syndrome (ARDS) to establish the nature of the increased venous admixture. Six animals served as controls and revealed no major changes apart from a 10% decrease in cardiac output during the 4-h observation period. All control animals showed a shift to a higher mean V/Q of perfusion (Qmean) and a maintained log standard deviation (QSD) throughout the experiment. The distribution was unimodal and centered around a V/Q ratio of 1.0. The share of perfusion to V/Q ratio less than 0.005 (i.e. true shunt, Qs) remained unchanged at 6-7% of cardiac output. Nine animals, given a continuous infusion of E. coli endotoxin, showed a significant decrease of 53% in cardiac output (Qt) at 4 h. Mean pulmonary artery pressure (MPAP) showed a 2-phase reaction with a peak level at 0.5 h, and a second gradual increase from 2 h onwards. Venous admixture doubled at 0.5 h, after which it declined but remained elevated throughout the observation period. All endotoxin animals showed a shift in perfusion to a higher Qmean with a significantly wider QSD at 0.5, 2 and 4 h. The distribution was unimodal and centered around a V/Q ratio of 1.0. True shunt was unchanged at 6-7% of cardiac output throughout the study. The increase in venous admixture in this experimental ARDS model is consequently explained by the widening of the V/Q scatter and is due to a perfusion shift to lower ventilation/perfusion ratios rather than to an increase in true shunt. PMID- 2588995 TI - Influence of the fluid balance on the cortisol and glucose responses to transurethral prostatic surgery. AB - The serum cortisol and blood glucose concentrations were followed for up to 2 h after 35 transurethral prostatic resections performed under epidural anaesthesia. No significant variation in either of these levels was recorded in connection with the seven operations during which there was no disturbance of the fluid balance, or the seven where there was elevation in the central venous pressure indicative of intravenous fluid overload. In contrast, both the serum cortisol and the blood glucose level showed a significant increase in the nine patients with a blood loss of more than 800 ml, and in the nine recording absorption of irrigant in excess of 300 ml and immediate development of hyponatraemia. On the other hand, this response did not occur in the three patients with irrigant absorption where hyponatraemia developed with a delay of at least 20 min. These results suggest that the effect of surgery on the serum cortisol and blood glucose levels may be modified by disturbances of the fluid balance developing in the course of the operation. PMID- 2588994 TI - Atelectasis and gas exchange impairment during enflurane/nitrous oxide anaesthesia. AB - The development of atelectasis and effects on gas exchange during enflurane anaesthesia in nitrogen/oxygen or nitrous oxide/oxygen (inspired oxygen fraction 0.4) were studied in 16 lung-healthy patients (mean age 49 years). Awake, no subject displayed atelectasis as assessed by computed x-ray tomography of the thorax. Pulmonary gas exchange, studied by multiple inert gas elimination technique, and blood gases were normal. After 10 min of enflurane anaesthesia in nitrogen/oxygen, 14 of 16 subjects had developed atelectasis. After 30 min of enflurane anaesthesia in nitrogen/oxygen or nitrous oxide/oxygen, all patients had developed atelectasis, and a further increase was observed after 90 min of anaesthesia to approximately 5% of the intrathoracic area. There was no difference between the two anaesthesia groups. In the nitrogen group, shunt rose to a maximum of 5.8% at 30 min of enflurane anaesthesia, with a significant reduction to the initial anaesthesia level after 90 min of anaesthesia (3.4%). Perfusion of poorly ventilated lung regions (low VA/Q) averaged 4-5% and did not vary significantly during the anaesthesia. In the nitrous oxide group, shunt increased to 6.3% after 90 min of anaesthesia, and there was a parallel decrease in perfusion of low VA/Q regions. The findings suggest that besides prompt collapse of lung tissue during induction of anaesthesia, absorption of gas from closed-off or poorly ventilated regions takes place and further increases the atelectatic area. PMID- 2588996 TI - Hemodynamic effect of epidurally administered epinephrine in middle-aged and elderly patients. AB - The circulatory effects of epinephrine, added to local anesthetic, during epidural analgesia were compared between middle-aged (52-65 years) and elderly (75-82 years) patients undergoing transurethral resection of the prostate. We used 10 ml of 1.5% lidocaine with or without 1:200,000 epinephrine. The plasma epinephrine concentration peaked 5-10 min after the injection in the patients who received epinephrine with anesthetic. There was no significant difference in the plasma epinephrine concentration between the two age groups. Epinephrine caused a significant increase in the heart rate and a significant reduction in the diastolic arterial pressure in both age groups. A significant reduction of the systolic arterial pressure, however, occurred only in the middle-aged patients. Neither the plasma concentration of endogenous epinephrine, heart rate nor arterial pressure changed significantly in the patients who received plain lidocaine. We conclude that the increase in the heart rate and decrease in the diastolic arterial pressure induced by epinephrine when added to an analgesic may not be influenced by advancing age. In contrast, the reduction in the systolic arterial pressure caused by epinephrine may become less pronounced with age. PMID- 2588997 TI - Spread of spinal anaesthesia using various doses of plain 0.5% bupivacaine injected at the LIV-V interspace. AB - Spinal anaesthesia with 3 ml, 4 ml or 5 ml of plain 0.5% bupivacaine was performed in three groups of 20 orthopaedic (ASA 1) patients at the LIV-V interspace. Patients aged less than 20 years or more than 60 years and those outside the normal range of body mass index were excluded. The spread of analgesia was greater in the 4-ml and 5-ml groups compared to the 3-ml group at each testing time (P less than 0.05). The mean maximum cephalad spread of pinprick analgesia (+/- s.d.) 60 min after injection was significantly higher (P less than 0.05) in the 4-ml group (T10 +/- 3.2) and in the 5-ml group (T10 +/- 2.7) than in the 3-ml group (T12 +/- 2.1). The interindividual variability of the cephalad spread of analgesia was greater in the 4-ml and 5-ml groups compared to the 3-ml group (P less than 0.05). The degree of motor block was higher in the 5 ml group than in the 3- and 4-ml groups at 5 and 15 min after injection. In seven patients the first sign of motor block was the patient's inability to flex the ankle, rather than inability to raise an extended leg as was the case in the other patients. In all patients satisfactory anaesthesia for surgery of the lower extremity was achieved. PMID- 2588998 TI - Effects of epidural analgesia on plasma calcitonin gene-related peptide. AB - The effects of epidural analgesia on plasma calcitonin gene-related peptide (CGRP) values during and after hysterectomy were investigated in 14 healthy patients. In seven patients who received general anaesthesia alone for pelvic surgery, there were no significant changes in plasma CGRP concentrations. In the remaining patients, who received extensive epidural blockade in addition to general anaesthesia, there were again no significant changes in plasma CGRP values. This was in spite of profound sympathetic blockade, as shown by marked hypotension and a significant decline in plasma catecholamines. The epidural group of patients showed the expected attenuation of the glucose, cortisol and growth hormone responses to surgery. The results show that circulating CGRP is unlikely to be involved in the modulation of peripheral vascular tone during pelvic surgery under either general or epidural anaesthesia. PMID- 2588999 TI - The association between the neuroleptic malignant syndrome and malignant hyperthermia. AB - The neuroleptic malignant syndrome (NMS) is an uncommon but dangerous complication of treatment with neuroleptic drugs. A primary defect in skeletal muscle has been suggested in view of similarities in the clinical presentations of NMS and anaesthetic-induced malignant hyperthermia (MH). The in vitro halothane-caffeine contracture tests are the most reliable method of identifying individuals susceptible to MH. The aim of this study was to define if a relationship exists between NMS and MH susceptibility. Hence, the in vitro halothane and caffeine contracture tests were performed on muscle tissue obtained from eight NMS, ten MH-susceptible and ten control patients. The results, which are expressed in accordance with the criteria of the European MH Group, defined the eight NMS subjects as MH non-susceptible. The response to halothane and caffeine exposure of skeletal muscle from NMS and control subjects was the same and significantly different from that of muscle from patients susceptible to MH. Furthermore, muscle from subjects in NMS and control group responded similarly to increasing concentrations of chlorpromazine. These results do not point towards an association between NMS and MH. PMID- 2589000 TI - Reversal of postoperative somnolence using a two-rate infusion of physostigmine. AB - In order to antagonize immediate postoperative somnolence, 24 surgical patients were given a two-rate infusion of physostigmine, aiming at a constant plasma concentration in the range of 1 to 10 ng/ml. Plasma concentrations of physostigmine were determined during infusion and after infusion and the effects of physostigmine on analgesia and postoperative sedation, and its side effects were monitored throughout. On the 1st postoperative day some of the patients (n = 8) were given 5 mg physostigmine orally, after which plasma concentrations as well as effects were measured. Steady-state concentrations were generally lower than predicted. Clearance varied between 10 and 85 ml/min x kg with a mean of 40.8 +/- 21.0 ml/min x kg. Oral bioavailability was 25.3 +/- 11.1%. Physostigmine administered as an intravenous infusion antagonized immediate postoperative somnolence in 21 out of 24 patients. Effects were poorly correlated with the established steady-state concentration of physostigmine. The patients' experience of postoperative pain relief was mostly satisfactory and the side effects of physostigmine infusion were generally limited. The effects of physostigmine in the immediate postoperative period seemed dependent on the dose as well as on the time which had elapsed since administration of anticholinergic drugs. After oral physostigmine administration the following morning, the majority of patients experienced side effects such as nausea and abdominal pain. In conclusion, physostigmine given as infusion antagonizes postoperative somnolence. However, the arousal effect was considered not better than that resulting from a bolus dose of the drug, although the infusion regimen allowed a prolonged clinical effect duration. PMID- 2589001 TI - Cyanide release from sodium nitroprusside during coronary bypass in hypothermia. AB - Erythrocyte cyanide levels were determined by a sensitive fluorimetric method on four occasions during coronary bypass in hypothermia in 18 consecutive patients treated with sodium nitroprusside (SNP) with an infusion rate less than 1 microgram x kg-1 x min-1. Every second patient received the cyanide antidote thiosulphate simultaneously with the SNP-infusion. At normal body temperature, as well as during hypothermia in cases receiving thiosulphate, the cyanide levels rose slowly but significantly with the infusion rate. Higher erythrocyte cyanide levels in relation to the infusion rates, up to 8.0 mumol/l, were found during hypothermia in two of the cases not receiving thiosulphate. We conclude that SNP is broken down to cyanide even under hypothermia and that low body temperature may impair the conversion of cyanide to thiocyanate, probably by affecting the metabolic pathways providing the sulphur substrate. This effect may add to other factors decreasing sulphur availability in critically ill patients, and simultaneous administration of thiosulphate is therefore recommended to ensure a safe SNP treatment during and after coronary bypass operations. PMID- 2589002 TI - Induction and recovery characteristics of propofol, thiopental and etomidate. AB - Propofol, thiopental and etomidate, with 20 patients in each group, were compared for anesthesia of short duration in women undergoing termination of pregnancy, with respect to: 1: pain on injection (equally often after propofol and etomidate, but more rarely after thiopental); 2: apnea following induction (no difference); 3: involuntary muscular movements more frequent after etomidate); 4: blood pressure (larger drop after propofol); 5: heart rate (greater increase after thiopental); 6: time to eye opening on command (longer after propofol); 7: Steward score on eye opening (no difference); 8: coin counting after 15, 30 and 60 min (performance better after propofol at 15 and 30 min, producing even shorter times than preoperatively at 60 min); 9: reaction time after 15, 30 and 60 min (performance better after propofol, producing even shorter times than preoperatively at 60 min. It is concluded that the faster recovery gives propofol an advantage over thiopental and etomidate in outpatient anesthesia. PMID- 2589004 TI - Acetylcholine receptor antibody in myasthenia gravis. AB - Radioimmunoassay techniques were used to detect antibodies to the acetylcholine receptor (AAChR) in 164 patients with adult-onset myasthenia gravis. AAChR levels above 0.6 nM/l were considered pathological and were found in 67% of the patients with an average value of 58.99 +/- 125.02 nM/l (0.6-900.0). Correlation, with clinical functional status, the histopathological thymus alterations and the different therapeutics used did not disclose any statistically significant differences. PMID- 2589003 TI - An evaluation of tests of psychomotor function in assessing recovery following a brief anaesthetic. AB - This study was designed to evaluate the usefulness of three commonly used tests of psychomotor function and one test of short-term memory in assessing recovery from a brief nitrous oxide, oxygen and halothane anaesthetic. Twenty-six female patients undergoing minor gynaecological surgery were allocated to one of three treatment groups depending on premedication (placebo, low dose and high dose). Immediate recovery was most rapid in the placebo group. Both the tests of simple reaction time and picture recall were able to differentiate between the post anaesthetic recovery of the high-dose group and that of the other two groups. Neither component of the letter cancellation test showed a clear difference in recovery pattern. Tests of critical flicker fusion were too unreliable to be of use in clinical decision making. Our results suggest that tests of reaction time and memory were more sensitive than letter cancellation in assessing recovery. PMID- 2589005 TI - Interleukin 1 and 2 production by peripheral blood mononuclear cells in subacute sclerosing panencephalitis and exacerbation of multiple sclerosis. AB - Il-1 and Il-2 production by peripheral blood mononuclear cells was studied in 10 patients with SSPE and 15 patients in the acute stage of MS. Both SSPE and MS cells in vitro released spontaneously high amounts of Il-1, and could not be further stimulated to synthesis of Il-1 by latex. The Il-2 production was decreased in both processes but in MS after the recovery from the acute stage the production of Il-2 increased. The role of the observed changes in both Il-1 and Il-2 secretion in the pathogenesis of SSPE and MS is unknown. PMID- 2589006 TI - Cognitive functioning after subarachnoid haemorrhage of unknown origin. AB - Twenty patients, who had sustained a proven subarachnoid haemorrhage (SAH) and in whom cerebral panangiography had failed to reveal any source of the bleeding (SAH NUD), were subjected to a neuropsychological examination involving memory functions, spatial perceptual organization, visuoconstructive abilities, reasoning, perceptual speed and accuracy, and concept formation. Cognitive functioning in SAH-NUD patients was compared with normal reference values and also related to the cognitive performance of neurologically intact patients having sustained an aneurysmal bleeding (SAH-AN). SAH-NUD patients showed significant reduction of verbal learning and retention, and of abilities involving abstract attitude and concept formation, i.e., functions related to frontotemporal structures. In all other respects the performance of these patients approached normality. Unexpectedly, there were no significant differences in mean test scores separating SAH-NUD from aneurysmal SAH patients. Collapsing the patient groups produced an increased number of significant deviations from normality, which was interpreted as the effect of the contribution of a greater number of relatively more impaired SAH-AN patients. This was supported by the finding that the ratio of impaired individuals to total number of subjects differed in the groups; the proportion of individuals showing cognitive sequelae was larger among SAH-AN patients throughout all comparisons but one. Although SAH of unknown aetiology represents much less of a catastrophe as compared with haemorrhage of aneurysmal origin, it does not preclude cognitive disturbances. Thus, the presence of blood per se anywhere in the subarachnoid spaces appears to affect higher brain function(s). PMID- 2589008 TI - Intracellular elemental composition of single muscle fibres in muscular dystrophy and dystrophia myotonica. AB - Seven patients with myotonic muscle dystrophy (MD), 6 with muscle dystrophy without myotonia (limb-girdle and facio-scapulo-humeral dystrophy) and 6 healthy volunteers were subjected to biopsy from the anterior tibial muscle (TA). Light microscopic examination of cryostat sections revealed pathological changes of different kind and degree--the occurrence of ring fibres and multiple central nuclei was the most consistent in advanced MD. X-ray microanalysis (XRMA) of single muscle fibres demonstrated the intracellular content of such elements as Na, Cl, K, Mg, S and P. The most conspicuous finding was the increase in Na and Cl and decrease in K demonstrated in MD. The highest levels of Na and Cl were found in ring fibres. Decrease in K was as high in structurally normal fibres of MD biopsies as in ring fibres and was also found in the muscle dystrophies without myotonia, but to a lesser degree than in MD. Thus, the decrease in K was not correlated to increase in Na and Cl. These changes in muscle fibre elemental content are discussed in relation to plasma membrane changes of erythrocytes in MD and especially the indications of disturbed anion channels. PMID- 2589007 TI - Spatial impairment following right hemisphere transient ischaemic attacks in patients without carotid artery stenosis. AB - Neuropsychological testing was performed on: 10 right-handed patients who had had 1-4 right hemisphere transient ischaemic attacks (TIAs), 10 normal controls, 10 house painters with long-term exposure to organic solvents, and 10 patients with liver cirrhosis. The subjects in each group were matched for age and education. No TIA patient had significant internal carotid artery stenosis, and CT was normal except in one patient, although magnetic resonance imaging (MRI) performed 3 years after the testing was abnormal in 4/8 cases. No patient reported additional distinct TIAs during the period between neuropsychological testing and MRI. The TIA patients showed lateralized signs of spatial impairment, whereas the cirrhotics and also (but to a lesser degree) the house painters showed signs of diffuse cerebral dysfunction. The study shows that hemispheric TIAs in patients without significant internal carotid artery stenosis may result in persistent focal cognitive impairment. This can be demonstrated with sensitive neuropsychological instruments even when MRI is normal. PMID- 2589009 TI - The role of infection and vaccination in the genesis of optic neuritis and multiple sclerosis in children. AB - This article describes the association between previous infection and/or vaccination and the development of optic neuritis (ON) in 18 children. Ten of these children subsequently developed clinically definite multiple sclerosis (MS), while in 8 patients a clinically definite etiology could not be confirmed. Vaccination preceded the first ON attack in 6 patients, all but one of whom subsequently developed MS. It also preceded subsequent demyelinating events in 6 patients. Ten of the patients had a bacterial or viral infection within the 2 weeks prior to the first symptoms of ON. Intrathecal antibody synthesis against 2 or more viruses could be shown in 5 out of 8 patients studied; 5 out of 6 patients had oligoclonal antibodies in CSF and 12 out of 16 patients a high IgG index. Neither intrathecal antibody synthesis against 2 or more viruses nor elevated IgG indexes could be found in the control patients. Measles and mumps occurred at a significantly later age in the children who subsequently developed MS than in the control children, and these patients had significantly more events that might have impaired the blood-brain barrier than the controls. These results indicate that immunological events leading to MS may be triggered during childhood. Vaccination and infection often precede ON in childhood. Intrathecal viral antibody production can occur already in childhood at the time of the first symptoms of MS. PMID- 2589010 TI - Conduction velocity study in type 1 diabetic patients. AB - The role of metabolic abnormalities in the development of diabetic neuropathy is controversial. To investigate the peripheral nerve function and the influence of hyperglycemia on nerve conduction in insulin-dependent diabetes, a one-year neurophysiological study was carried out in 30 type 1 diabetic patients ranging in age from 2-16 years. During the 12-month follow-up period the glycosylated hemoglobin determination, motor conduction velocity of the peroneal nerve and the motor and sensory conduction of the tibial nerve were assessed 3 times, at the beginning of the study and every 6 months thereafter. The sensory latency was found significantly delayed in these patients as compared with the controls. The degree of sensory conduction slowing correlated well with the glycosylated hemoglobin concentrations and improved with the reduction in hyperglycemia. PMID- 2589011 TI - Magnetic resonance imaging--a method of studying the size and asymmetry of the planum temporale. AB - The planum temporale is a triangular region on the upper surface of the temporal lobe. This area of the brain is important for language processing and shows a left-right asymmetry of size in most brains. Particular interest has been focused on the size and asymmetry of the planum temporale in brains of individuals with developmental dyslexia. Magnetic resonance imaging (MRI) is a method that produces excellent morphological details of organic structures. We have developed an MRI method of studying the size and asymmetry of the planum temporale in human brains. Because of considerable variation of anatomical landmarks in this cortical region of the brain, an evaluation of asymmetry is not possible in all brains. Furthermore, our experience with this method indicates that any indirect imaging technique of studying asymmetry of the planum temporale must be evaluated with caution. With this in mind, however, MRI may give valuable anatomical information about the planum temporale in individuals with anomalous language function. PMID- 2589012 TI - Determination of urine thiocyanate in patients with amyotrophic lateral sclerosis. AB - It has been reported that amyotrophic lateral sclerosis-Parkinsonism-dementia in Guam might be related to the eating of Cycas seeds, which contain cyanide. Based on this assumption, we determined the urinary thiocyanate excretion level in patients with ALS and compared this with that of other neurological diseases. The assay method was designed to use column chromatography with Amberlite IRA 402. The thiocyanate level was determined using pyridine-barbiturate method. The 24-h thiocyanate level was higher in the ALS patients of the middle stages than in the normal control group (Wilcoxon's test, P less than 0.02). There were no significant differences between the ALS patient groups of the early and terminal stages, Kugelberg-Welander disease group, Duchenne type muscular dystrophy group and control group. From these results, we concluded that ALS patients were contaminated with cyanide or thiocyanate and that, along with rapid muscular atrophy, the thiocyanate excretion levels were high. PMID- 2589013 TI - Myelopathy of unknown etiology. A clinical follow-up and MRI study of 57 cases. AB - After a careful differential diagnosis of 264 consecutive cases of spinal cord syndrome seen over a period of 10 years, no diagnosis was reached in 72 patients. Of these cases, known as myelopathy of unknown etiology (MUE), 57 were followed up for a mean of 2.33 years, 50 being chronic cases and 7 acute cases. Diagnosis was reached in 29 (58%) of the 50 chronic cases, the remaining 21 (42%) still being of unknown etiology. The most frequent diagnosis was either definite or probable multiple sclerosis (MS). Magnetic resonance imaging (MRI) was of great value in detecting asymptomatic brain lesions. We conclude that after a long clinical follow-up and the use of MRI we were able to diagnose more than half the previously MUE patients. PMID- 2589014 TI - CSF choline and acetylcholinesterase in early-onset vs. late-onset Alzheimer's disease patients. AB - Cerebrospinal fluid acetylcholinesterase (AChE) activity levels and choline (Ch) levels were studied in 52 dementia of Alzheimer type (DAT) patients and 20 age matched controls. The AChE activity was significantly lower and Ch levels were significantly higher in DAT patients than the age-matched controls. There was no significant difference in AChE activity and Ch levels between early-onset (less than or equal to 65 years) patients and late-onset (greater than 65 years) patients. However, the AChE activity was significantly lower in early-onset patients compared with their age-matched controls but no difference was observed in late-onset patients compared with their age-matched controls. None of the biological measures (AChE, Ch) were significantly correlated with the degree of cognitive impairment, duration of the illness or the sex of these patients. PMID- 2589015 TI - Sleep tonus inversion: a feature of juvenile dystonic parkinsonism. AB - Polysomnographic monitoring of a 16-year-old girl suffering from dopa-responsive dystonic parkinsonism showed a change in the distribution of muscle activity in thigh muscles during different stages of sleep. The hamstring muscles were hypertonic at sleep onset compared with the vastus lateralis of the quadriceps muscles. At the third sleep cycle of each of the 2 nights, the time at which sleep benefit becomes clinically evident, the hypertonia in the hamstring muscles was reversed and the vastus lateralis became more hypertonic. It is suggested that the muscle tonus inversion marks the moment at which the sleep process alleviates the dystonic parkinsonian state manifested at wakefulness as a circardian fluctuation. According to our data, the flexor-extensor tonus inversion during sleep was not yet described in the literature, and may be an associated feature of dopa-responsive dystonic parkinsonism. PMID- 2589016 TI - Glial fibrillary acidic protein and cartilage. AB - The presence of glial fibrillary acidic protein was tested for in cartilage of bronchi, trachea, pulmonary hamartomas, articular cartilage and chondrosarcomas. The cytoplasm of most chondrocytes in bronchi stained strongly positive, whilst in hamartomas only small foci at the edges reacted. Staining in the trachea was weak. In chondrosarcomas a few cells were positive, but most areas were negative. Articular cartilage was consistently negative. Young chondrocytes expressed the antigen more strongly than mature cartilage. Dedifferentiated cartilage cells such as chondrosarcoma react, in contrast to their cells of origin in articular cartilage. PMID- 2589017 TI - Chronic idiopathic ataxic neuropathy: neuropathology of a case. AB - A case of chronic, sporadic, slowly progressive, purely sensory, ataxic neuropathy is reported. In previously published similar cases only muscle and nerve biopsies have been available for study. In the present case the patient died of an unrelated illness 39 years after onset of the neuropathy. A full neuropathological study was performed. The disease process was limited to the dorsal root ganglia and their central and peripheral processes. Large myelinated fibers were preferentially involved. Involvement of the dorsal root ganglia has also been reported in certain toxic ganglioneuropathies and in the sensory neuropathy associated with carcinoma. The long duration and insidious development set the present case apart from those conditions. An inflammatory component was lacking. Except for a microscopic focus of adenocarcinoma of the prostate no malignancy was present. The etiology of chronic idiopathic ataxic neuropathy is unknown, but it is likely that the dorsal root ganglion is the main target for the disease process in most if not all cases. PMID- 2589018 TI - Regression of perineurial cell basement membrane in a human diabetic following isogenic pancreas transplant. AB - Perineurial cell basement membrane (PCBM) thickening is a consistent feature in diabetes mellitus (DM) and may have relevance to the cause of DM neuropathy. In this ultrastructural morphometric study of identical twins discordant for DM, we found that the PCBM was significantly thicker in the dermal nerves of the diabetic twin. Following pancreas transplantation (PT) and a 2-year period of euglycemia, the PCBM in both dermal and sural nerves was significantly thinner. At the end of the 2nd year post-PT, the PCBM thickness in the dermal nerves of the diabetic was not significantly different from the non-DM twin. The correction of diabetic dysmetabolism may have played a role in the regression of PCBM. These data suggest that PCBM thickening may not be a permanent legacy of DM. PMID- 2589019 TI - Focal spinal muscular atrophy in two German shepherd pups. AB - Focal spinal muscular atrophy evolved rapidly in two German Shepherd pups 2 weeks after birth. By 1 month, the male and female littermates had developed a valgus deformity of the right forelimb, a flexed carpus, and arm and forearm muscle weakness and atrophy. In the male, less severe left forelimb weakness and wasting also occurred, and bilateral forelimb denervation potentials were recorded. Postmortem study of the male revealed asymmetric loss and degeneration of motoneurons in the cervical spinal cord intumescence. Degenerating neurons appeared vacuolated or chromatolytic. Chromatolysis was often peripheral and resulted from dispersion and loss of the free and attached ribosomes which normally from Nissl bodies. Although this focal neuronopathy was unlike motoneuron diseases described previously in animals, it resembled the asymmetric and unilateral, benign spinal muscular atrophies found in humans. PMID- 2589020 TI - Pathological studies of aberrant peripheral nerve bundles of spinal cords. AB - Aberrant peripheral nerve fiber bundles, i.e., masses of peripheral nerve fibers without perineural sheath cells, are found in the perivascular spaces of some spinal cords. The 514 spinal cords examined for these structures were separated into two groups; 507 spinal cords without definite necrotic lesions (group 1) and 7 spinal cords (group 2) with old necrotic lesions in which there were numerous aberrant peripheral never bundles (APNB). In group 1, APNB were found in 41.0% of spinal cords. The incidence was the same for both sexes and increased in proportion to age. APNB were found predominantly in the middle and lower thoracic segments. On the transverse sections, APNB were located mainly in the central gray matter and in the anterior median fissure. Ultrastructural and histochemical studies showed that the myelin in APNB was peripheral in origin. Serial sections showed continuity between APNB and nerve roots. In group 2 cases, APNB were diffusely distributed throughout the old necrotic lesions and not restricted to perivascular areas. PMID- 2589022 TI - An immunohistochemical analysis of T cells in primary B cell malignant lymphoma of the brain. AB - An immunohistochemical study was performed on small lymphoid cells present in frozen tissue sections of seven cases of primary B cell malignant lymphomas of the brain by using monoclonal antibodies to T cell (Leu-1, OKT-11, Leu-3a, and Leu-2a) and B cell (BA-1 and Leu-12) surface markers. In all the seven cases, positive reaction for Leu-1 and OKT-11 was seen in the majority of the small lymphoid cells which were dispersed among the lymphoma cells or clustered around blood vessels. The large neoplastic cells were unstained by these antibodies. Staining for T cell subsets with antibodies to Leu-3a and Leu-2a showed heterogeneous staining in each case. The ratio of Leu-3a+ to Leu-2a+ cells was less than one in six cases, demonstrating a suppressor/cytotoxic phenotype predominance. Most of these small lymphoid cells were negatively stained by antibodies to BA-1 and Leu-12. From these findings, it was shown that the small lymphoid cells observed in primary B cell lymphomas of the brain were of T cell lineage, distinct from the neoplastic cells, and probably reactive in nature. The implications of these findings are discussed. PMID- 2589021 TI - Primary malignant lymphoma of the brain: demonstration of immunoglobulin gene rearrangements in four cases by the Southern blot hybridization technique. AB - Using the Southern blot hybridization technique, four cases of the primary malignant lymphomas of the brain, histologically diffuse large cell lymphoma, were examined for the immunoglobulin gene rearrangements. In three lymphomas, the rearrangements were observed in both heavy and light chain genes, providing strong evidence for a B cell lineage of these tumors. On the other hand, in the remaining lymphoma, the rearrangement was observed only in the heavy chain gene. Despite this, immunohistochemical examination revealed positive stainings for heavy and light chain immunoglobulins in tumor cells, suggesting the occurrence of light chain gene rearrangement at the undetectable level. Thus, B lymphocytic differentiation at the gene level was demonstrated in three, or possibly all, of the primary intracerebral malignant lymphomas examined. Since no more than two rearrangements were detected in each immunoglobulin gene, these lymphomas were considered to be monoclonal in nature. PMID- 2589023 TI - Establishment of a human glioma cell line bearing a homogeneously staining chromosomal region and releasing alpha- and beta-type transforming growth factors. AB - A human glioma cell line (YKG1), which was positively identified for glial fibrillary acidic (GFA) and S-100 proteins, was established from a surgical specimen of a patient with glioblastoma. Chromosome analysis of the cells revealed a homogeneously staining region (HSR) on a marker chromosome. The assay for transforming growth factors (TGFs) in the conditioned medium of the cell line revealed that it contained high levels of alpha- and beta-type TGFs, which might regulate the growth of glioblastoma and influence on the peritumoral tissues. PMID- 2589024 TI - Establishment of a monoclonal antibody against senile plaques and its application for immunohistological and immunoelectron microscopical studies in the brain of the elderly. AB - A monoclonal antibody (Am-3) was produced against senile plaques in the brain of a patient with Alzheimer's disease. Am-3 was reactive with senile plaques of typical, primitive and diffuse type not only in the brain used as immunogen, but also those in the brain of 15 out of 25 autopsy cases of the aged people. Moreover, Am-3 was also reactive with granular materials of various sizes scattered in the 1st, 3rd and 4th layers of the cerebral cortices of the cases with severe dementia. Am-3 was also reactive with vessel wall of the congophilic angiopathy. By immunoelectron microscopic examination, Am-3 was positive with amyloid fibril in the core and crown of senile plaques, and in the congophilic angiopathy. PMID- 2589025 TI - Computerized three-dimensional reconstruction of the developing blood-brain barrier. AB - Computer-aided techniques for three-dimensional reconstruction of images were employed in a morphological and morphometrical study of blood-brain barrier (BBB) development in the microvasculature of the chick embryo optic tectum. The method proved very useful for understanding the spatial relationships between BBB vascular and perivascular components, and of their modifications during embryonic life. The results indicate that the perivascular astrocytic endfeet, the main periendothelial components of the BBB, appear on the 14th incubation day and form an almost continuous perivascular envelope at hatching time. PMID- 2589026 TI - Peripheral motor neuropathy in spontaneously diabetic WBN/Kob rats: a morphometric and electron microscopic study. AB - The morphology and function of peripheral motor nerves of WBN/Kob rats of the newly identified strain with late onset and long-lasting diabetes were studied in comparison with those of nondiabetic age-matched rats. The most conspicuous and frequent change seen by electron microscopy in the diabetic rats was myelinopathy, initiated by vesicle formation in granular material accumulated in the myelin lamella. Initial changes developed into myelin blebbing or distention, demyelination and remyelination. A decreased population of nerve fibers in diabetic rats of advanced age suggested that the final stage of these changes was neuronal loss resulting from complete destruction of the neurons. The myelinopathy was consistently more frequent and conspicuous in diabetic rats than in age-matched nondiabetic rats, but the difference was not significant in rats of over 28 months old, because of the age-dependent increase of the change in older rats. The conduction velocity was significantly less in diabetic rats than in age-matched nondiabetic animals at 20 months but not at 28 months of age, because at the older age nondiabetic rats also showed a reduced conduction velocity. These findings showed that male WBN/Kob rats develop diabetic motor neuropathy, but that the essential changes in diabetic neuropathy are indistinguishable morphologically and functionally from those in age-dependent neuropathy. PMID- 2589027 TI - Immunohistochemical localisation of terminal complement component C9 in experimental allergic encephalomyelitis. AB - The deposition of terminal complement component C9 within the central nervous system (CNS) has been studied immunohistochemically in three models of experimental allergic encephalomyelitis (EAE) in the rat; inflammatory EAE induced by the passive transfer of myelin basic protein-specific T cells (tEAE), antibody-mediated, demyelinating tEAE and a subacute/chronic model induced by active immunisation with guinea pig spinal cord tissue in adjuvant. Two distinct patterns of C9 reactivity were observed, a diffuse staining of the tissue adjacent to inflammatory lesions, similar to that seen for other extra-vasculated serum proteins, and also granular, sometimes fibrillar C9 deposits around some inflammed vessels and in areas of active demyelination. The latter staining pattern was most pronounced in animals with acute antibody-mediated demyelinating tEAE, in which extensive, but transient, subpial and perivascular granular deposits of C9 were associated with regions of acute demyelination. A similar pattern of granular C9 reactivity was also associated with demyelinating lesions in animals with actively induced chronic progressive EAE. However, these C9 deposits were not observed in rats with purely inflammatory, clinically mild tEAE, although C9 deposition was occasionally observed around a small number of inflammed vessels in animals with hyperacute, lethal tEAE. These observations demonstrate that deposition of C9, the major component of the cytolytic membrane attack complex, in EAE is related to myelin injury rather than CNS inflammation. PMID- 2589029 TI - Serum levels of antibodies against Actinobacillus actinomycetemcomitans in various forms of human periodontitis. AB - Serum levels of IgG, IgA, and IgM antibodies against extracts from Bacteroides gingivalis PER8, Actinobacillus actinomycetemcomitans Y4, and Bacteroides fragilis NCTC 9343 were determined in three categories of periodontitis patients by means of enzyme-linked immunosorbent assay. The test groups comprised 10 patients with juvenile periodontitis (JP), 18 young patients with severe periodontitis (YP), and 31 patients with adult periodontitis (AP). Nine subjects with healthy periodontium (HP) served as a reference group. Increased frequencies of patients with significantly elevated IgG and IgA antibody values against B. gingivalis and A. actinomycetemcomitans were found in the three periodontitis groups as compared with the HP group. The AP group, however, showed lower IgM values than the other groups. The results support the contention that A. actinomycetemcomitans may play a contributory role in adult periodontitis and that B. gingivalis is a suspected periopathogenic bacterium in juvenile periodontitis. The clinical YP classification was not supported by the present serologic findings. PMID- 2589028 TI - Membranous changes in primary malignant CNS lymphomas. AB - Ultrastructural studies of 17 primary malignant CNS lymphomas revealed 6 tumors with abnormal intracytoplasmic and/or intranuclear membranous structures, most frequently associated with the endoplasmic reticulum or perinuclear envelope. In most cases, tubuloreticular inclusions and paired cisternae were present. Less frequent were accumulation of microtubules, concentric lamellar bodies, and rod like or paracrystalline intranuclear inclusions. The specificity and significance of these membranous structures remain questionable because of their frequent occurrence in a variety of normal and pathological conditions. Some of these changes may be considered as cellular reactions to viral infections, others may indicate cellular activity or degeneration. PMID- 2589031 TI - Craniomandibular disorders and general joint mobility. AB - The purpose of the investigation was to study the relationship between general joint mobility and dysfunction among patients with craniomandibular disorders (CMD). Joint mobility was assessed in 74 female patients and 73 controls, using Beighton's modification of the Carter & Wilkinson hypermobility score. Twenty five (83%) of 30 patients with score greater than or equal to 3 (lax joints) had temporomandibular joint (TMJ) involvement. Eighteen (41%) of 44 patients with score 0-2 (no laxity) had TMJ involvement. The difference between these groups was statistically significant (p less than 0.001). General joint laxity should therefore be taken into consideration in diagnosis and treatment of CMG. PMID- 2589030 TI - On the presence and localization of epidermal and nerve growth factors in human whole saliva. AB - Using antibodies to mouse submandibular epidermal growth factor (EFG) and nerve growth factor (NGF), immunohistochemical studies were performed on sections of flash-frozen human whole saliva in both light and transmission electron microscopy. Light microscopy showed the presence of overall network-like immunoreactions in both the EGF and NGF antibody-treated sections. Electron microscopy showed clearly detectable ultrastructural reaction patterns for both growth factor antibodies. The individual structural elements were more distinct for the EGF antibody-treated sections, in which the reaction elements had approximate diameters of 0.05 micron. In the NGF antibody-treated sections the corresponding approximate diameters were 0.02 micron. In both the EGF and NGF antibody-treated sections heavily stained bacteria-like particles were also frequently observed. PMID- 2589032 TI - Mandibular dysfunction in adulthood in relation to morphologic malocclusion at adolescence. AB - The purpose of this 20-year follow-up study was to assess whether pronounced morphologic traits of malocclusion, persisting from adolescence to about 35 years of age, imply an increased risk of persistent and severe mandibular dysfunction. In 1965-66 malocclusion was recorded in 176 adolescents; in 1981 these persons responded to a questionnaire concerning symptoms of functional disorders, and in 1986-87 malocclusion and signs of dysfunction were registered. Highly significant associations were observed between some of the self-reported symptoms and the signs registered 5-6 years later. Spearman correlation coefficients between the persistent traits of malocclusion, occurring at both examinations, and the signs of mandibular dysfunction were low in general. No association was found between the most severe and persistent functional disorders and any particular malocclusion. It is concluded that orthodontic screening of morphologic malocclusion in childhood would seem of limited value in attempts to predict mandibular dysfunction in adulthood. PMID- 2589033 TI - Sugar consumption and caries experience in 12- and 13-year-old Icelandic children. AB - Dietary habits with regard to sugar consumption and caries experience were studied in a group of 275 Icelandic children aged 12 and 13 years. The pattern of meals and sugar-containing food intake frequency were assessed by means of a dietary questionnaire. All dental examinations were performed by one examiner, using standardized methods and diagnostic criteria. Only 75% of the children had three regular meals daily. Breakfast and lunch were the most frequently omitted meals. Sweet buns were consumed by 32% of the children with meals and by 58% between meals, whereas soft drinks were consumed by 42% and 46%, respectively. Eighty-three per cent of the children reported eating sweets daily. The most popular products included confectionery, buns, cakes, and soft drinks, which constituted 53% of the intake with meals and 68% of that between meals. A higher caries incidence was associated with frequent intake of buns and cakes with meals and confectionery. PMID- 2589034 TI - Centers of rotation during jaw movements. AB - Anatomists consider the articulation of movable joints to be complex, involving movable instantaneous centers of rotation (ICR). However, prosthodontists often treat the temporomandibular joint (TMJ) as a model of a simple hinge. The aim of this study was to examine the case for a movable ICR during habitual opening and closing jaw movements. Young, dentate subjects were examined with a kinesiograph. Jaw movements were performed and recorded. The center of rotation of each movement pattern was identified, and its location related to the position of the TMJ. The results showed that opening and closing jaw movements were predominantly non-coincident, with a movable ICR located at a variable distance and direction from the TMJ. There was no evidence to suggest that the TMJ functioned as a simple hinge during jaw movements. PMID- 2589035 TI - Reproducibility of estimation of blood flow in the human masseter muscle from measurements of 133Xe clearance. AB - The reproducibility of estimations of the masseter intramuscular blood flow (IMBF) was assessed bilaterally within and between clinical sessions. The 133Xe clearance in nine normal individuals was measured before, during, immediately after, and after endurance of isometric contraction at an attempted level of 50% of maximum voluntary clenching contraction. An overall low reproducibility of the estimations was found. This result was probably caused by uncertainties about the exact site of intramuscular 133Xe deposition, errors in assessment of the plots of clearance, and variabilities in the relative contraction levels sustained and, especially, in the overall muscle effort. In agreement with previous reports concerning other skeletal muscles, the 133Xe clearance method provided inconsistent estimates of absolute values of IMBF also in this clinical setting. Although there was a high intra-individual variation in the relative level of isometric contraction sustained, the endurance test induced distinct changes in IMBF, among which the estimate of post-endurance hyperemia was the most consistent for each individual. Therefore, measurements of 133Xe clearance seem to be useful to detect intra-individual changes in masseter IMBF resulting from isometric work. PMID- 2589036 TI - Classification of perinatal and late neonatal deaths in Iceland. A survey from a defined population. AB - A retrospective case record analysis of all perinatal and late neonatal deaths in Iceland in the periods 1976-80 and 1981-85 was done and the causes of death classified according to the extended Aberdeen classification. There was a significant (p less than 0.0001) reduction in number of deaths between the two periods with perinatal mortality rates declining from 10.6/1000 in 1976-80 to 6.8/1000 in 1981-85. In 1976-80 there were 81 (33%) antepartum, 37 (15%) intrapartum and 128 (52%) neonatal deaths compared to 61 (38%) antepartum, 13 (8%) intrapartum and 86 (54%) neonatal deaths in 1981-85. Fetal abnormality was the most common cause of death in both periods followed by the category Low birthweight in 1976-80. In 1981-85 increased morphological detection of infection in infants of very low birthweight by placental examination and autopsies lead to a shift from the category Low birthweight to Maternal Disease, the second most common cause in that period. To achieve lower perinatal mortality rates efforts should be directed towards lowering antepartum losses near term and increasing survival of very low birthweight infants. PMID- 2589037 TI - Can we expect to lower perinatal and neonatal mortality? AB - In a retrospective study of all perinatal and neonatal deaths in Iceland in 1976 85, the circumstances surrounding each death were carefully evaluated to assess the quality of care given and to identify cases of suboptimal care. In 1976-80, 87 or 35% of peri- and neonatal deaths were associated with suboptimal care and 46 or 29% of peri- and neonatal deaths in 1981-85. Most of the infants weighed more than 1500 g. Suboptimal care was most commonly seen in conjunction with antenatal care in both five-year periods, with a 25% (N.S.) reduction of cases in 1981-85. Suboptimal intrapartum care was significantly reduced (p less than 0.05) and there was a substantial reduction (62%), although not significant (0.1 greater than p greater than 0.05), of suboptimal neonatal care between the two periods. A few cases were attributable to maternal decisions taken against medical advice, most of them in the latter period. Perinatal care improved during the study period. The task of further lowering perinatal mortality rates depends on vigilance to abnormal findings in routine antenatal care. PMID- 2589038 TI - International collaborative effort (ICE) on birth weight, plurality, perinatal, and infant mortality. III: A method of grouping underlying causes of infant death to aid international comparisons. AB - Underlying causes of infant death, as coded in the ninth revision of the International Classification of Diseases, have been grouped into a system of seven functional categories plus one additional group of "other and unclassifiable" diagnoses. The groups comprise congenital anomalies, asphyxia related conditions, immaturity related conditions, infections, sudden death, deaths due to external causes, and other specific conditions. The groups were constructed by using a frequency distribution of underlying cause of death in 200,000 infant deaths in 1980-84 in the U.S.A. When analysed according to age at death and according to birth weight, the distribution of the functional groups had patterns which corresponded to what might be expected clinically. Each functional group has common features which require intervention at a specific time for prevention and treatment. We propose that it is used as a tool in epidemiological surveillance and to guide health authorities in priorities for disease control. International comparisons of time trends will be undertaken. PMID- 2589039 TI - Maternal heart disease. A survey of a decade in a Danish university hospital. AB - Among 87 pregnancies complicated by heart disease, delivered during the decade 1977-86, 70 (81%) had a congenital heart malformation, 7 (8%) an acquired heart disease and 10 (11%) arrhythmias or conduction disturbances. The incidence was 0.3%. The corresponding data from a report from Rigshospitalet during the 1950s were: 42%, 49%, and 9%, respectively, and an incidence of 0.9%. Ventricular septal defect (VSD) and atrial septal defect (ASD) were the most frequent malformations. The women were classified according to the NYHA before, during and after the pregnancy. All women except 4 re-entered their original functional class. In 51 cases, ECG showed completely normal sinus rhythm, while in 36, various degrees of arrhythmia or conduction disturbance were found as well as left or right ventricular hypertrophy and/or strains. Nine infants had congenital defects, 4 of which were a heart malformation (4.6%). One infant died. Gestational duration, weight and perinatal mortality did not differ significantly from that of the general population. Two women died, one of primary pulmonary hypertension and one with a rupture of the thoracic aorta. Rheumatic heart disease is no longer a significant factor in relation to pregnancy in Denmark, but congenital heart disease is still of great importance, because more survive and reach the age of fertility. Today most women can be brought safely through pregnancy, but obstetric, cardiologic and anesthesiologic expertise is still mandatory for a successful course and outcome of pregnancies complicated by heart disease. PMID- 2589040 TI - Alleviation of labor pain in Norway. An interview investigation in 1969 and 1986. AB - In 1969 the Scan-Gallup institution interviewed a random sample of 503 women from all parts of Norway who had given birth during the last 24 months. Cesarean sections and forceps deliveries were excluded. The interviews revealed that 69% of the women were left unattended for a considerable part of the delivery, that their husbands were present at only 6% of the births, and only 31% of the women received any kind of analgesia. None were given an epidural block. Nevertheless, 80% of the mothers subsequently said they were satisfied with the treatment and care. Of the 20% dissatisfied, 70% complained of lack of attention, but only 17% drew attention to lack of analgesia. The same investigation has been repeated in 1986 by the same institution and using the same questions. This time the interviews disclosed a completely different picture. 83% of the women were attended by someone all the time during their births, the child's father was present at 86% of the births, 75% of the mothers had received some kind of analgesia, and 14% received epidural block. Nevertheless, the number of satisfied mothers was no greater than in 1969. In 1986 the dissatisfied complained of unfriendly midwives, and lack of sympathy, reassurance and support. Only 15% complained of lack of analgesia, similar to the 1969 finding. PMID- 2589041 TI - Pre-eclampsia--a mitochondrial disease? AB - Mitochondrial dysfunction is a newly found group of inborn errors of metabolism in which there is a failure in the aerobic energy production. Disorders of mitochondrial metabolism exhibit a wide range of clinical symptoms which are related to the nature, severity and tissue distribution of the metabolic defect. Most reported cases are published in the neurological literature. In this report we describe for the first time a family with mitochondrial dysfunction with a high incidence of pre-eclampsia/eclampsia. The diagnosis of a mitochondrial disorder is verified by electronmicroscopic, electromyographic, histochemical and biochemical examinations. During pregnancy, the energy demand is increased due to both fetal and maternal requirements. A mitochondrial dysfunction, clinically symptomless in the non-pregnant state, may therefore become manifest during pregnancy. Characteristic features of pre-eclampsia such as disturbed ion transport, disturbed prostaglandin synthesis, vasoconstriction, platelet aggregation and hyperuricemia may be explained by mitochondrial dysfunction. PMID- 2589042 TI - The prognosis in early endometrial carcinoma. The importance of uterine papillary serous carcinoma (UPSC), age, FIGO grade and nuclear grade. AB - 278 patients with either stage I or II endometrial carcinoma treated between January 1979 and January 1982 were reviewed, particularly as regards certain prognostic factors. Uterine papillary serous carcinoma (UPSC), FIGO grade 3, nuclear grade 3, and age were the major independent prognostic factors. UPSC was diagnosed in 8% of the patients. The cancer mortality in the non-UPSC group was 7%, vs. 41% in the UPSC group. In the latter group all the deaths occurred within 2 1/2 years. Poorly differentiated non-UPSC had the same cancer death rate as UPSC, but usually had a completely different histological pattern. There was no significant difference in survival between stage I and stage II when corrected for FIGO grade and nuclear grade. PMID- 2589043 TI - Addison's disease and pregnancy. AB - Five case reports are presented illustrating that pregnancy and Addison's disease are not incompatible, provided adequate substitution therapy is given. PMID- 2589044 TI - Bilateral female pelvic actinomycosis. AB - A case of bilateral actinomycotic salpingitis is described. The woman used an IUD and the course of the disease was protracted. Later, Actinomyces israelii was coincidentally identified from vaginal cultures. Attention is drawn to the need for distinction between the presence of Actinomyces israelii and actinomycosis. PMID- 2589045 TI - Classification and audit of perinatal deaths: the Icelandic and other examples. PMID- 2589047 TI - Epidemiological and social aspects of perforating eye injuries. AB - The epidemiology of 387 consecutive perforating eye injuries (PEI) treated at the Helsinki University Eye Hospital in 1980-1986 was evaluated. Eighty-six percent of patients were males. The age group of 16-45 years predominated among males, 0 15 years among females. The mean age of all patients was 33.7 years. Forty percent of the male injuries were occupational, 38% domestic and 11% caused by assault. The corresponding figures for females were 9%, 53% and 23%, respectively. The occupation groups most often associated with accidents at work were construction (42%) and industry (30%). Five percent of all PEIs were caused by traffic accidents, and 3% were sports-related. After treatment 91% of the economically active patients were able to return to their pre-accident work, 4% had to change profession, and 5% became permanently disabled and unable to work. PMID- 2589046 TI - Prognosis of perforating eye injuries with intraocular foreign bodies. AB - The long-term results of 95 consecutive eyes with a perforating eye injury and an intraocular foreign body (IOFB) treated with or without pars plana vitrectomy are reported. With the mean follow-up time of 30.0 months (median 22.8 months) 10 eyes (11%) were enucleated and another 17% became blind (visual acuity less than 0.05). The enucleation rate was considerably decreased and the visual outcome improved as compared with previous studies in Finland. The visual outcome was affected unfavourably by posterior location of the perforation, blunt injury, prolapse of intraocular tissue and poor initial visual acuity. There was no significant difference in the visual outcome between eyes with posterior segment IOFBs treated with or without vitrectomy. In the posterior perforation group the visual outcome was slightly better in eyes in which vitrectomy was performed (P = 0.336), and early vitrectomy within 1 week gave best visual results (P = 0.692). In 79% of the non-enucleated eyes the retina was attached. The anatomic success rate was similar regardless of the timing of vitrectomy. PMID- 2589048 TI - Incidence of endophthalmitis in Sweden. AB - A retrospective review of all suspected and proven cases of endophthalmitis (EO) during a period of 18 months in Sweden is presented. This period covered the time of transition in the surgical technique at a large number of clinics. Sixty-two cases of EO were reported out of which 52 were post-operative. A total incidence of post-operative endopthalmitis (POE) was found to be 0.33%. The incidence of culture proven POE was however only 0.06%. No cultures or only conjunctival cultures had been taken in 32 (61.5%). S. epidermidis and S. aureus comprised the majority of isolates. No case of fungal EO was reported. The number of posttraumatic EO was low. PMID- 2589049 TI - Visual outcome of endophthalmitis in Sweden. AB - A retrospective study of 62 cases of clinically diagnosed endophthalmitis (EO) reported from 24 clinics in Sweden was carried out. Both culture negative and positive cases were included. The function of the eye was lost in 34% of all cases, while vision better than 0.1 was preserved in 41% cases. Staph. epidermidis positive and culture negative cases were associated with better visual results. The majority of eyes with cultures positive for Staph. aureus were lost or became blind. Intravitreal injection of antibiotics and vitrectomy was generally reserved for more severe cases often involving a delay in their institution. A combination of topical and systemic steroids gave better results than no steroids or only topical steroid administration. PMID- 2589050 TI - Protection against cataract by aspirin, paracetamol and ibuprofen. AB - Results of a case-control of 423 cataract patients and 608 controls in Oxfordshire shows that the protective effect against cataract associated with consumption of aspirin-like analgesics (aspirin, paracetamol and ibuprofen family) is manifest even at low doses. Less than 150 g total dose was associated with a halving of the risk of cataract extraction. PMID- 2589051 TI - Blinking and corneal sensitivity. AB - We have investigated the relationship between corneal sensitivity and blinking patterns. Using a group of 9 young normal subjects, measurements were made of blink patterns, central and peripheral corneal sensitivity and lid margin sensitivity both before and after use of topical corneal anaesthetic, proxymetacaine hydrochloride (Alcaine). Blink patterns were recorded through concealed filming and were later analysed in terms of blink frequency and the type of blinks (proportion of complete, incomplete, twitch and forced blinks). Blink rate was significantly lower following anaesthetic administration, but the relative proportion of blink types remained unchanged. We speculate that one of the factors responsible for normal involuntary blinks is the imminent break-up of the tear film which is sensed by the cornea. PMID- 2589052 TI - Central visual function in patients with resolved central serous retinopathy. A long term follow-up study. AB - The visual acuity, central retinal sensitivity, macular thresholds, contrast sensitivity and temporal visual acuity were employed to assess the long term visual outcome in 23 patients with a history of central serous retinopathy (CSR). Twenty patients had unilateral CSR, and 3 had had bilateral disease. The unaffected eyes had significantly better visual acuities (P less than 0.014), better retinal sensitivities (P less than 0.006) and lower macular thresholds (P less than 0.008) when compared with affected eyes. The eyes with CSR whose visual acuities were mildly affected (6/9) showed lower sensitivity for the high spatial frequency (P less than 0.0072). There was no significant difference in the temporal visual acuity between eyes with CSR and the non-affected eyes. PMID- 2589053 TI - The influence of the learning effect on automated perimetry in patients with suspected glaucoma. AB - The influence of the learning effect on the outcome of automated perimetry was studied as a function of eccentricity. The same comprised 20 patients with suspected glaucoma who were all naive to automated perimetry. Visual field examination of the right eye followed by that of the left eye was undertaken on each of three successive days and after a further interval of 12 days using a customized full-field program of the Humphrey Field Analyser 630 (stimulus size III). The program comprised 60 points out to an eccentricity of 60 degrees with an interstimulus grid of 12 degrees. Global, central, peripheral, superior and inferior mean sensitivity each significantly increased (P less than or equal to 0.01) from the first to the second right eye examinations and from the third to the fourth left eye examinations (P less than or equal to 0.01). The global short term fluctuation, central mean defect and number of stimulus presentations decreased from the first to the second right eye examination (P 0.01). The order of examination between eyes and the interval between examination sessions influences the response recorded by automated perimetry. PMID- 2589054 TI - Non-stereo fundus photography as a screening procedure for diabetic retinopathy among patients with type II diabetes. Compared with 60D enhanced slit-lamp examination. AB - The spectrum of diabetic retinopathy, the need for fundus screening and the evaluation of two presumptive screening methods, was investigated in a population based study among patients with type II diabetes. Retinal evaluation was performed in 86.9% of the known diabetic population. Background diabetic retinopathy was detected in 37.8%, pre-proliferative in 1.1% and proliferative retinopathy in 3.8%. Diabetic maculopathy was found in 24.3% of the patients. Laser therapy was considered in 11.4% of the patients due to diabetic retinopathy, and in 14.6% when venous occlusive diseases were included. Two methods, a slit-lamp observation enhanced by a 60D lens and reading from two non stereo photographs of the posterior pole, were evaluated among 154 patients willing and mentally capable of being examined by either method. The sensitivity of the photographic method was 87/97% (right eye/left eye) when detecting background retinopathy and 81/80% for maculopathy versus 69/61% and 79/63%, respectively, with the slit-lamp method. The photographic method could be applied in 93% of the patients mentally capable of cooperation. Only 5 or 6 patients could be examined per hour with the 60D slit-lamp compared with 30-35 examined by reading retinal photographs. The photographic method is recommended as an easy and reliable screening device for diabetic retinopathy among patients with type II diabetes. PMID- 2589055 TI - Non-stereo photographic screening after panretinal photocoagulation for proliferative diabetic retinopathy. Compared with 60D enhanced slit-lamp examination. AB - 135 patients treated with panretinal photocoagulation for proliferative diabetic retinopathy were examined in order to detect 7 specific fibrovascular lesions after treatment. Two presumptive methods for long-term follow-up were evaluated and compared, i.e. slit-lamp biomicroscopy enhanced by a 60 D lens and reading from two non-stereo photographs of the posterior pole. Two observers repeated their examinations with respective methods. Comparison of the methods with respect to detecting ability of the fibrovascular lesions showed no significant disagreement except in some eyes with fibrous tissue on the optic disc where new vessels were better detected with the slit-lamp method (P less than 0.001). There was no difference between the methods with respect to the intra- and inter observer variability. Twenty to 30 patients could be diagnosed per hour with the photographic method compared to 5-6 patients with the slit-lamp. Two non-stereo photographs of the posterior pole can be recommended as a safe and time-saving method for objective documentation and long-time follow-up after panretinal photocoagulation for proliferative diabetic retinopathy. PMID- 2589056 TI - Long-term visual results in eyes cured for retinoblastoma by radiation. AB - Twenty-four eyes from 18 patients cured for retinoblastoma by radiation on an average 12 years previously, were re-examined with respect to visual performance. The macular functions, i.e. visual acuity, colour vision and contrast sensitivity demonstrated performances predictable from tumour localization and radiation dose to the macula. The rod functions, i.e. visual field and dark adaptation were found to be relatively resistant to the radiation treatment. A special problem encountered in two-eyed patients was the unavoidable amblyopia due to unequal handicaps in the two eyes at the vulnerable age. PMID- 2589057 TI - Evaluation of the Keeler Pulsair non-contact tonometer. AB - The recently-introduced Pulsair non-contact tonometer (Keeler Instruments, Inc, Broomall, PA) was evaluated against the Goldmann applanation tonometer in cannulated post mortem human eyes, and in living subjects at three clinical centers. Statistical analysis of the findings revealed strong linear relationships between Goldmann or manometric and Pulsair intraocular pressure readings, with correlation coefficients ranging from 0.79 to 0.97. However, with the Pulsair reading as the dependent variable, the slope of the relationship in each case was significantly less than 1.0 (range 0.65 to 0.83), while the intercept was positive (range 1.31 to 2.33 mmHg). Thus, the Pulsair tended to read low at intraocular pressure above the normal range. Conversion factors and a calibration table allowing intraocular pressure estimates more comparable to Goldmann tonometry using the current (J-series) Pulsair are provided herein. A calibration algorithm could be integrated into the circuitry of future production models of the Pulsair instrument. PMID- 2589058 TI - Determination of Na and K in the rat lens by atomic absorption spectrophotometry. AB - A new procedure is described for determination of sodium and potassium in rat lenses with atomic absorption spectrophotometry. Samples were prepared by soaking of the ground or the intact lens in deionized water. For potassium determinations HNO3 dissolution was also tried. Deionized water or CsCl aqueous solution was adopted for dilution for measurement. At absorbances up to 1.0 absorbance unit only measurements on HNO3 dissolved lenses diluted in deionized water were compatible with a linear absorbance function. At absorbances below 0.2-0.3 absorbance units all combinations were in agreement with a linear absorbance function. Grinding of the lens was found to increase the variability but did not change the level. HNO3 dissolution did not increase the level. Dilution with CsCl increased the sensitivity and decreased the variability. A schedule is proposed for determination of sodium and potassium in which lens samples are obtained by soaking in deionized water. Aqueous solution of CsCl is suggested for dilution. PMID- 2589059 TI - Do intraocular lenses with ultraviolet absorbing chromophores protect against macular oedema? AB - In a prospective study, designed to test the effect of intraocular lenses containing an ultraviolet absorbing chromophore on the incidence of post operative cystoid macular oedema, 55 patients undergoing extracapsular cataract extraction were randomly allocated to receive intraocular lenses with or without an ultra-violet absorbing chromophore. Post-operative fluorescein angiography showed no difference in the incidence of macular oedema in those patients receiving an intraocular lens with an ultraviolet absorbing chromophore compared with patients receiving a standard posterior chamber intraocular lens. PMID- 2589060 TI - Experiences with a new corneal suction trephine. AB - The importance of exact trephining for successful keratoplasty is well known. We employ a new suction trephine, thus obtaining exact and sharp cutting margines which are examined by scanning electron microscopy (SEM). The first observed clinical results in 25 cases are good. PMID- 2589061 TI - Energy levels and outcome of ALT by 0.1 s and 0.2 s burns. PMID- 2589062 TI - Nystagmus responses in a group of normal humans during earth-horizontal axis rotation. AB - Horizontal eye movement responses to earth-horizontal yaw axis rotation were evaluated in 50 normal human subjects who were uniformly distributed in age (20 69 years) and equally divided by gender for each decade. The subjects were rotated with eyes open in the dark, using clockwise and counterclockwise 60 degree/s velocity trapezoids. The nystagmus slow component velocity (SCV) was analysed using four parameters: Amp, Bias, Mod and Tau. Amp and Tau characterize the canal-ocular reflex to constant velocity steps, while Mod and Bias characterize the "AC" and "DC" components of the otolith-ocular reflex. Results indicated that intersubject variability was larger than that seen in earth vertical axis data. Tau depended significantly (p less than 0.05) upon subject gender, while Mod increased monotonically with age decade. Linear regression showed a positive correlation between pairs of SCV magnitude parameters (Amp, Bias and Mod), suggesting a common scaling effect. In addition, there was a negative correlation between the value of the decay time constant Tau and each of the three magnitude parameters. Thus, despite large intersubject variability, parameters that describe earth-horizontal yaw axis responses are loosely interrelated and some of them vary significantly with gender and age. PMID- 2589063 TI - Circularvection about earth-horizontal axes in bilateral labyrinthine-defective subjects. AB - A stationary subject surrounded by a visual display rotating about an earth horizontal axis typically experiences a sensation of continuous self-rotation (vection) coupled with a paradoxical sensation of a limited degree of body tilt, both opposite to the direction of the stimulus. The sensation of limited body tilt has been attributed to conflict between visually-induced vection, and otolithic and somatosensory graviceptive information which indicates that the body has not moved. We investigated circularvection and illusory body tilt about the horizontal axis in the pitch and roll planes in bilateral labyrinthine defective (L-D) subjects. Results demonstrated that the bilateral group experienced complete unambiguous self-rotation through an upside-down orientation. The relative contributions of the otolithic and somatosensory graviceptors to visuall-induced tilt is discussed. PMID- 2589064 TI - The plasticity of compensatory eye movements in bilateral vestibular loss. A study with low and high frequency rotatory tests. AB - Twelve subjects with bilateral vestibular loss, with a mean age of 27 years (18 49) were studied. The loss was based on symptoms of oscillopsia and ice-water caloric tests. Nine subjects were evaluated by low-frequency sinusoidal harmonic acceleration (SHA) rotatory tests (0.01-0.32 Hz), and 3 subjects with high broad frequency band rotatory tests (0.25-3.25 Hz). During alertness tests (darkness) all subjects had absent or very low gains. When tested with a stationary light in the middle of the swing, the SHA tests showed perfect compensatory eye movements with gains of 1 and phases of approximately 0 degrees. In the broad-frequency test, the gain was near 1 below 1 Hz, decreasing rapidly at higher frequencies. In imaginary stationary target tests (darkness), the gain was enhanced to 'normal' values (0.5) with a phase lead in the low-frequency range (SHA). This could not be replicated in the high-frequency tests. Testing with stationary acoustic guidance (darkness), further enhanced the gain in the SHA tests. A small increase of gain could also be found in the high-frequency tests. Compensatory eye movements, when tested in low-frequency rotatory tests (less than 1 Hz), are to a large extent influenced by non-vestibular mechanisms. By voluntary modifications, normal gains could be produced by patients with 'bilateral vestibular loss'. The phase lead found is proposed to be of central non vestibular origin. Testing in higher frequency ranges (greater than 1 Hz) could not replicate these findings, thus the broad-frequency band rotatory test should be preferred for adequate vestibular quantification. PMID- 2589065 TI - Rotational responses in patients with bilateral caloric reduction. AB - Caloric irrigation and earth vertical axis rotation, both horizontal semicircular canal stimuli, occasionally provide conflicting information about the presence of bilateral vestibular loss. The caloric and rotational responses of an unselected group of 1274 dizzy patients were compared to identify discrepancies between the two tests. Results indicated a poor correlation between the magnitude of response to caloric and rotational stimuli; about half of patients with reduced caloric responses (total eye speed less than or equal to 10 degrees per second) had rotational response magnitudes (at 0.05 Hz and above) that were within normal limits. Our findings confirm that bilateral caloric reduction is not sufficient evidence for diagnosing bilateral vestibular loss and indicate that, in some case, caloric responses may be absent despite apparent normal vestibular sensitivity as assessed by rotational testing. PMID- 2589066 TI - Head-shaking nystagmus: associations with canal paresis and hearing loss. AB - In 108 patients referred for caloric testing, head-shaking nystagmus (HSN) was noted in 37 electronystagmography (ENG) recordings. A canal paresis was found in 31 patients and a sensorineural or mixed hearing loss in one or both ears was found in 45 patients. Both HSN and canal paresis were insensitive predictors of either hearing loss or of each other. HSN was less sensitive as well as less specific than canal paresis for hearing loss. These data suggest that HSN is not as powerful a test as canal paresis in detecting lesions of the 8th nerve. PMID- 2589067 TI - Correlation between velocity step and caloric response parameters. AB - The correlation between velocity step (VS) and caloric response parameters was studied in a series of several hundred patients who underwent a neuro-otological examination. The VS parameters initial velocity (V in degree/s), time constant (T in s) and Gesamtamplitude G ( = VT in deg) were all significantly correlated with the caloric response parameters. The highest correlation coefficients were associated with G. PMID- 2589068 TI - Effects on the vestibulo- and opto-oculomotor system in rats by lesions of the commissural vestibular fibres. AB - Eye movements were recorded from rats with a magnetic search coil system before and after sectioning of the midline commissural pathways in the brain stem at the level of the vestibular nuclei. After lesion, the findings were as follows: 1) During sinusoidal vestibular stimulation the eyes moved in a sinusoidal way similar to the head movement without any regular saccades. There was a reduced gain and a phase lead. 2) During optokinetic stimulation the eyes moved in the stimulus direction to an excentric position and stayed there until stimulation ceased. 3) During acceleratory/deceleratory rotation in the light there was a drift of the eyes in the direction of the expected slow phase movement to an excentric position. In some animals there was a directional asymmetry. The findings may be explained by a failure of the central neural integrator for horizontal eye movements. The results support the hypothesis that vestibular commissural fibres are of crucial importance for the function of this integrator system. PMID- 2589070 TI - Peripheral facial palsy caused by the Borrelia spirochete. AB - Forty-three consecutive patients with peripheral facial palsy were examined to evaluate the incidence of facial palsy caused by the tick-borne Borrelia spirochete in a non-coastal area in the south of Sweden. Six (14%) of the patients were found to have a Borrelia infection. The incidence of Borrelia induced facial palsy was 0.39/10,000 inhabitants, which is less than in neighbouring coastal areas but still high enough to cause serious concern when dealing with facial palsies. In contrast to Bell's palsy, a Borrelia infection can cause serious generalized illness if not properly treated. Negative Borrelia serology of the serum and the cerebrospinal fluid (CSF) and a normal CSF analysis did not exclude the Borrelia etiology. Tick bites, signs of polyneuropathy, meningeal symptoms and Borrelia-associated erythema proved to be important signs for the diagnosis. PMID- 2589069 TI - Dynamic changes following combined treatment with gentamicin and ethacrynic acid with and without acoustic stimulation. Cellular uptake and functional correlates. AB - Regional selectivity of gentamicin (GM) ototoxicity was studied in guinea pigs (GPs) using electrophysiological, morphological, autoradiographic and immunohistological observations following combined treatment with GM (150 mg/kg i.m.) and ethacrynic acid (EA) (30 mg/kg i.c. or i.v., 1.5 h after GM injection). The GPs were either continuously stimulated every 5 min with a series of 256 clicks (70 dB peSPL, 10/s) during 3 h for monitoring fast changes in VIII nerve compound action potential (CAP) after the EA injection, and thereafter kept in the animal quarters (background noise of 60 dB SPL) (group I), or similarly monitored for only 10 min after the EA injection and thereafter kept in a soundproof room (around 0 dB SPL) (group II). Whenever GM labelling was observed it was localized only in the sensory hair cells. From 3 h after EA injection, the GPs in group I presented threshold elevations in the high-frequency region, which progressed to 60-80 dB at all frequencies at and after 48 h. Parallel to the threshold pattern, GM uptake in outer hair cells (OHCs) was seen with an increasing concentration from apex toward base from 3 to 24 h, while after 48 h almost all OHCs were destroyed and inner hair cells (IHCs) were marked by GM. In group II no changes in CAP thresholds were observed until more than 24 h, although GM was detected in the hair cells from 6 h on. At this early stage, the distribution of GM lacked a clear pattern, particularly without a clear apex-base gradient, and GM deposits were found only around the basal body. However in both groups, in late stage (greater than 24 h), the base-apex gradient was more pronounced and GM was found throughout the cell body, with a marked concentration below the cuticular plate. These results suggest that GM may penetrate hair cells around the basal body and that activating the cells by sound potentiates both GM uptake and its intracellular toxicity. PMID- 2589071 TI - A comparison of topical EMLA cream and Prilocaine injection for anaesthesia of the tympanic membrane in adults. AB - To date there is no ideal method of painlessly achieving anaesthesia of the ear drum for myringotomy and grommet insertion. In this double blind, placebo controlled prospective study we have assessed a new topical anaesthetic agent (EMLA Cream) for use on keratinised squamous epithelium. A comparison has been made with the anaesthesia achieved by an injected agent. Twenty individuals were randomly allocated to receive placebo or EMLA cream. Their relative discomfort was measured on a visual analogue scale. Ten individuals received injected anaesthetic prior to myringotomy and grommet insertion and the discomfort of injection and of the procedure were similarly measured. We found EMLA cream to be an equally effective method of anaesthetising the ear drum as an injected agent. In addition there was minimal discomfort in the achievement of this anaesthesia. The discomfort of injecting the ear canal is shown to be similar to that of performing myringotomy and grommet insertion without anaesthesia. PMID- 2589072 TI - The ultrastructure of lymphatic vessels in the human middle ear with cholesteatoma. AB - Lymphatic vessels were few in the edematous portion of the cholesteatoma perimatrix of the human middle ear. But the lymphatic vessels contained mucus and consisted of degenerated endothelial cells. Edema of the perimatrix was considered to be caused by the degeneration of lymphatic vessels. Normal lymphatic vessels were found in the fibrous perimatrix, while macrophages infiltrated and phagocytosed cell debris. In addition, regenerating blood vessels were observed. Degeneration of connective tissue due to lymphatic edema and its repair were both present in the perimatrix. The degeneration of perimatrix was hypothesized to be caused by confined mucous epithelium behind the cholesteatoma matrix. PMID- 2589073 TI - Late results of treatment with ventilation tubes for secretory otitis media in ENT practice. AB - Ventilation tubes were inserted in 262 children aged 0-9 years for secretory otitis media in the period 1975-78. Treatment according to earlier described procedures during the intubation period, including a final check 3 months and 1 year after extrusion, were done. If recurrences were observed, retubulation was performed. 191 patients (73% (355 ears] have been re-evaluated in February, 1986, to February, 1987, mean observation period 7 1/2 years. Clinical information was obtained. Otomicroscopy, including pneumatic otoscopy, impedance and pure-tone audiometry, has been carried out. Flaccida retractions of varying degree were present in 21% of the ears. Atrophic scars were present in 28%; no case of complete atelectasis was found. Perforations were seen in 2%. Myringosclerosis was seen in 48%. No cholesteatoma or meningitis was found or reported in the entire material. 99% had a pure-tone average (500, 1,000, and 2,000 Hz) of 20 dB HL or less (5 dB, 60%). Treatment with a ventilation tube seems to give the least complications when installed early in life. The importance of careful follow-up is emphasized. We recommend otomicroscopy at each control check, especially 3 months and 1 year after extrusion. PMID- 2589074 TI - On the diagnosis and pathogenesis of intramural maxillary cysts. AB - In order to study the etiology of the intramural maxillary cyst, which is the origin of the choanal polyp, an antrotomy was performed on 27 patients with such cysts. The cyst-fluid was analysed with respect to protein distribution and bacterial growth. The findings indicate an inflammatory process characterized by high concentrations of immunoglobulins and by consumption of complement and antiproteases. The growth of bacteria, primarily an oral flora found in the cyst fluids studied, and the sites of cyst attachment, may indicate an epithelial residue of the dental list as the origin of the intramural cyst. It is further suggested that bacterial substances will provoke an inflammatory response, giving rise to an expansion of the cyst. In all cases studied, the cyst-fluid was capable of gelling after a couple of minutes at room temperature. This observation seems to be a reliable diagnostic procedure at antral aspiration, distinguishing the cyst-fluid from the serous transudate of the serous sinusitis, which according to our results, does not have this capacity to form a gel. PMID- 2589075 TI - Motor and sensory fibers of the superior laryngeal nerve in the rat. A light and electron microscopic study. AB - A quantitative and qualitative study of the superior laryngeal nerve (SLN) and its branches was performed on the intact nerve and after experimental denervation procedures. The distribution patterns of the myelinated fibers of the intact internal (SLNI) and external (SLNE) branches in the rat were unimodal with a fiber diameter range of 0.5-12 microns and with peaks at 2-4 microns. Numerous unmyelinated fibers, ranging in diameter from 0.1-2.3 microns, were evenly distributed all over the nerve. The SLNI contained no degenerated myelinated fibers after intracranial vagotomy, but about 25% of the unmyelinated fibers showed degenerative features. In the SLNE 2-10% of the myelinated fibers and about 25% of the unmyelinated fibers were degenerated after the same procedure. Extracranial vagotomy caused degeneration of nearly all fibers in the SLNI and SLNE. Single unmyelinated fibers appeared normal after this procedure. Occasional myelinated and a few unmyelinated fibers were degenerated after excision of the superior cervical ganglion. It is inferred from the results that a majority of the myelinated fibers in the SLN (96-99%) are sensory, with the cell bodies in the extracranial vagal ganglia. The SLNE was also found to be predominantly sensory, as only 2-10% of the myelinated fibers and about 25% of the unmyelinated fibers had their cell bodies in the brainstem. Single myelinated and a few unmyelinated fibers in both the SLNI and SLNE had their origin in the superior cervical ganglion. PMID- 2589076 TI - Radiation therapy in early glottic cancer. Analysis of 177 consecutive cases. AB - Early vocal cord carcinomas (TiS or T1) in a consecutive series of 177 patients treated by primary radiotherapy over a 10-year period 1970-79 at the Department of General Oncology, Radiumhemmet, Karolinska Sjukhuset, were analysed regarding treatment results. In 137 cases the tumours were invasive (T1N0M0) and in 40 cases carcinoma of in situ type (TiS). Patient were treated with cobalt 60 gamma irradiation in fractions of 2 Gy up to a total dose of 64 Gy delivered as split course (CRE=17.8). Minimum follow-up time was 5 years. Tumour recurred in 21 cases (12%). All but 4 patients were rescued by subsequent surgery, giving 98% total survival. Treatment failures after primary radiotherapy were analysed in detail. Failures could not be attributed to treatment irregularities. No difference in pretreatment tumour size was detected when cured patients were compared with patients who relapsed. Biological factors that cause a relative radioresistance are considered to be the main reason for radiotherapy failures in early glottic cancer. PMID- 2589077 TI - Anti-hypercholesterolemic effect of melatonin in rats. AB - The effects on plasma lipids of daily intraperitoneal injections of 4 mg of melatonin (N-acetyl-5-methoxytryptamine) for 10-27-day periods were examined biochemically and morphologically in rats fed regular and high-cholesterol (1% cholesterol, 0.5% cholic acid) diets. Melatonin administration had no significant effect on plasma lipids and lipoproteins in the rats on a normal diet but blunted the effects of a high-cholesterol diet on these parameters. No effects of melatonin on lipase activity were noted. Melatonin also diminished the fatty infiltration in the liver of animals on the high-cholesterol diet. The high cholesterol diet produced major increases in VLDL and LDL cholesterol and protein content, and decreases in HDL cholesterol and protein. Melatonin decreased the extent of this plasma lipoprotein increase, although it did not completely prevent the phenomenon. Therefore, the effect is thought to be quantitative and not qualititative in nature. PMID- 2589078 TI - Effects of serum deprivation on Ki-67-reactive antigen. Expression in HeLa cells. AB - In order to elucidate the relationship between the level of cellular Ki-67 reactive antigen and cell proliferation activity, the effects of serum deprivation on the antigen expression and cell proliferation of HeLa cells were investigated using flow cytometry. The antigen was constitutively expressed in almost all cells cultured in normal medium containing 10% calf serum. In the serum- deprived cells, the antigen-negative fraction increased with culture time, and the level of Ki-67-reactive antigen fell rapidly during the first 24 h. The reduction in the antigen caused by serum deprivation was independent of the cell cycle phase. Both BrdUrd incorporation and the S phase fraction were diminished during the experiment with evidence of cell growth retardation. However, after refeeding with fresh normal medium, the antigen level that had been reduced by serum deprivation recovered to the level of the control cells within 24 h. These results suggest that the level of Ki-67-reactive antigen in cells reflects their growth condition. PMID- 2589079 TI - Multicentric astrocytomas of the optic chiasm, brain stem and spinal cord. AB - Autopsy was performed on a 52-year-old man with a 20-year history of neurological symptoms. At autopsy, both a brain stem tumor and a spinal cord tumor were found. These showed the features of pilocytic astrocytoma histologically. A pilocytic astrocytoma was also found in the optic chiasm upon microscopical examination. These three tumors were thought to be multicentric astrocytomas, because there was no continuity among them and no evidence of dissemination or metastasis by any pathway. From a review of the literature, the present case is considered to be an exceedingly rare one because of the multicentric sites of occurrence. PMID- 2589080 TI - Blastic transformation of essential thrombocythemia. A case report. AB - A case of blastic transformation of essential thrombocythemia (ET) is reported. A 69-year-old male was first admitted to hospital because of fever in February, 1982. He was diagnosed as having ET because of marked thrombocytosis (205.5 x 10(10)/1), absence of erythrocytosis, absence of splenomegaly, normal karyotype and no increment of blasts in the bone marrow, and normal levels of neutrophil alkaline phosphatase, vitamin B12 and folate. He was treated with busulfan, and subsequently his platelet count was well controlled for about five years. At the second admission, blasts were present in the peripheral blood, and later accounted for 49% of the total leukocyte count. Histological examination of a bone biopsy specimen showed homogeneous proliferation of blastic cells and slight reticulin fibrosis. At autopsy, the degree of bone marrow fibrosis had increased. This was considered to be a very rare case of ET with blastic transformation in the terminal phase. PMID- 2589081 TI - Heterogeneity, distribution and endogenous phosphate content of KCl-myosins prepared from different parts of human brain. AB - Myosin concentrations and their endogenous phosphate (P) content as well as some of their properties were investigated in different parts of the central nervous system (CNS). Myosin concentration in hemispherial part is in the average 40 mg/100 g fresh mince, but it varies between 5 mg and 30 mg myosin depending on the mental activity or accidental brain diseases. This refers to the other parts of CNS, too. A myosin may be isolated with a single and sharp peak as far as the gel filtration profile is concerned in spite of the high lipid content of the brain. Working with minimal lipid and RNA content requires a careful procedure by an experienced person. In spite of any careful isolation procedure, purified KCl myosin preparations are composed of at least two isomyosins each formed from different heavy chains. Myosins are localized in different parts of the cell, mitochondrial, synaptosomal and neuroplasmic, respectively. Brain myosins have higher endogeneous P concentrations than other cell-myosins. In hemispherial myosins the P-concentrations are high. Subjects trained in mental activities have the highest myosin and P concentration. We suggest that the role of myosin may directly be connected with cytokinetic motions even in case of the higher functions of brain cells like thinking, paying attention and memory, respectively. PMID- 2589082 TI - Learned control of systolic blood pressure raising and lowering in rhesus monkeys. AB - Three male monkeys (Macaca mulatta) were operantly conditioned to raise and lower systolic blood pressure (SP). All animals were trained in three stages: first to lower, then to raise systolic pressure, and finally to alternate these two behaviors. All monkeys learned the task and performed reliably in all stages. Diastolic pressure (DP) usually paralleled systolic pressure but changed much less than SP. Heart rate (HR) always fell below baseline in lowering sessions, and in two of the three animals during raising sessions as well. These findings support our earlier results which showed that monkeys could learn to control heart rate. This animal model should permit detailed studies of the hemodynamic mechanisms mediating learned control of systolic pressure. PMID- 2589083 TI - Tolerance to morphine induced by chronic mild environmental stressors. AB - Pain-sensitivity as well as the analgesic and thermoregulatory effects of morphine were studied after two different types of chronic environmental stresses in rats (extra stimulation of newborns for 21 days, or social isolation for a month in adult age). The basal pain sensitivity and the base-line body temperature were similarly affected after the two interventions: an increased tail-flick latency, a decreased hot-plate latency and a decreased body temperature were noted. The analgesic and thermoregulatory effects of morphine were uniformly reduced in rats exposed to either stress. These findings suggest a common effect of various non painful mild environmental stresses on the activity of the endogenous opioid system. PMID- 2589084 TI - Photoperiodic ovarian response in yellow-throated sparrow, Gymnorhis xanthocollis: involvement of circadian rhythm. AB - The experiments aim to investigate the mechanism of photoperiodic time measurement during photoperiodic ovarian response of subtropical yellow-throated sparrow. Groups of the photosensitive female birds were exposed to various night interruption cycles for a period of 35 days. These light-dark cycles consisted of a basic photophase of 6h and 1h photointerruption of the 18h dark phase in 24h cycle at different points. A control group was also placed under 7L/17D. Ovarian response was observed in the night-interruption cycles in which the photointerruption of dark phase was made 12h after the onset of basic photophase. The results are consistent with the Bunning hypothesis and indicate that an endogenous circadian rhythm is involved in photoperiodic time measurement during initiation of ovarian growth in this species. PMID- 2589085 TI - The prevalence of cognitive impairment in an elderly Canadian population. AB - We investigated cognitive impairment in a study of the health of the elderly population of Saskatchewan. Surveys of elderly persons living at home (n = 1267) and living in long-term care facilities (n = 990) were conducted in 1981. Cognitive impairment was assessed by a short 10-item mental status questionnaire previously validated against a clinical diagnosis of dementia in an elderly Canadian population. The prevalence of clinically significant cognitive impairment was found to increase with age and with dependence level in long-term care facilities. We estimate that 7.8% of the elderly population have cognitive impairment consistent with a clinical diagnosis of dementia. Our estimates are compared with those derived from other studies. These findings affirm the importance of dementia as a cause of dependence in the elderly and the need for long-term care facilities to deal with dementia and its consequences. Also, since at least as many persons with cognitive impairment live at home as in long-term care facilities, health care planners must direct attention to the elderly with dementia at home. PMID- 2589087 TI - An epidemiologic study of alcohol use as a predictor of psychiatric distress over time. AB - This longitudinal epidemiologic study examined how levels of psychiatric distress over one year may be influenced by both concurrent levels of alcohol use and by prior drinking levels. The study's data were gathered during the 1981-1982 Eastern Baltimore Mental Health Survey (EBMHS), as part of the 5-site National Institute of Mental Health Epidemiologic Catchment Area (NIMH-ECA) Program. The 2091 respondents (18-64 years of age) reinterviewed after one year were initially selected by means of multistage probability sampling of adult household residents in eastern Baltimore, Maryland. The findings for men and women indicated that both high psychiatric distress at baseline interview and concurrent heavy alcohol use were associated with higher levels of psychiatric distress at one-year follow up. Differences across population subgroups were also noted. Among women, the results further suggested that prior heavy alcohol use was an additional predictor of psychiatric distress levels after one year; this was not found for men. PMID- 2589086 TI - Relationship between psychiatric distress and alcohol use: findings from the Eastern Baltimore Mental Health Survey. AB - This study examined the nature and strength of relationships between levels of alcohol use and concurrent psychiatric distress among adults in the community aged 18-64 years. Data for this project were gathered by standardized interview methods during the 1981-1982 Eastern Baltimore Mental Health Survey. The 2558 survey respondents were initially selected by means of multistage probability sampling of adult household residents in eastern Baltimore, Maryland. This project's findings indicated gender differences in the relationships under study. There was a moderate degree of association between heavy alcohol use and psychiatric distress among women; at moderate levels of alcohol use, a modest association was also noted. In contrast, for males, the results suggested a small positive association between heavy alcohol use and concurrent psychiatric distress, although these findings were not conclusive. PMID- 2589088 TI - Further evidence supporting the role of the serotonin system in suicidal behavior: a preliminary study of suicide attempters. AB - The 3H-imipramine binding parameters (Bmax and Kd) were studied in platelets from female suicide attempters and from healthy volunteers. The Bmax was significantly lower among suicide attempters, with no modification of the Kd. These results provide support of the hypothesis that decreased serotonin function may play a role in suicidal behavior. PMID- 2589089 TI - Ego functioning predicts first-year status in adults with anorexia nervosa and bulimia nervosa. AB - Severe personality disturbance is a feature that possibly explains chronicity in eating disorders, a largely inexplicable development in terms of previously investigated factors. We tested this hypothesis in a group of 41 anorectics and bulimics with ratings of 13 ego functions and of status at 1-year follow-up. Patients who still were preoccupied with weight or shape and had a DSM-III-R eating disorder at follow-up had more severe ego disturbance at initial presentation than those who were free from symptoms. The relevance of demographics, syndromal diagnosis and clinical factors other than ego functioning was limited. The importance of ego functioning for prognosis in eating disorders thus appears to overshadow that of several factors that have been extensively cited in the literature. PMID- 2589090 TI - The truth about suicide in Portugal. AB - It seems odd that male suicide rates have decreased in Portugal over the last few years, whereas the opposite has happened in most other countries. In order to investigate the reasons for such a decrease, suicide rates were compared with controversial cases (ICD-9 category E 980-989) and with homicide rates. The results show that, since 1980 and coinciding with the use of ICD-9, controversial cases have increased 12 and 21 times among males and females respectively. The profile of controversial cases is similar to that of suicide according to sex, age, marital status and season. Rates for homicide have remained steady and have a distinct profile. It is concluded that since 1980 there has been a significant underreporting of suicides in Portugal, which have been registered as controversial cases. The difficulty of investigating and preventing suicide with such statistical data is stressed; an improvement in suicide reporting and registering is urgently required. PMID- 2589091 TI - Working ability of mentally ill people in times of social crisis. AB - In Yugoslavia a special commission evaluates the working abilities of insured ill people. In the last 14 years the number of people referred to this commission has increased. For people assessed as being unable to work the most frequent diagnoses have been psychiatric and cardiovascular diseases. All individual requests for retirement on partial or full pension based on mental disorder (n = 1563) made in 1982 in Bosna and Herzegovina were studied. People who were awarded pensions were also followed up. The results obtained indicated that the willingness to retire is widespread among insured people, quite often regardless of the actual impairment of their working abilities. Data are interpreted in the light of the severe socioeconomic crisis Yugoslavia has been experiencing through the last decade. PMID- 2589092 TI - An ethological approach to autism: an analysis of visual behaviour and interpersonal contact in a child versus adult interaction. AB - Eighteen children classified into 4 diagnostic categories were compared based on their behaviour in a child-adult interaction. The categories consist of autistic children with full syndrome, autistic children in a residual state, hyperactive children, and mentally retarded children. An ethological analysis of the interpersonal distance, the amount of physical contact, and the direction of the look/gaze was carried out to describe some behavioural aspects of infantile autism. The autistic children with full syndrome were found to be different from the other categories by a relatively close interpersonal distance, a high frequency of physical contact, and a low frequency of "look at face". PMID- 2589093 TI - Retirement, aging, psychosocial adaptation and mental health. Findings of the TURVA project. AB - This article deals with certain preliminary findings obtained in a long-term prospective study begun in 1982 using the interview method; the first follow-up was carried out in 1986, the method consisting of a postal inquiry and the collection of recorded data. The sample consists of 200 randomly selected inhabitants of Turku born in 1920 and 189 individuals of the same age living in rural municipalities in the vicinity of Turku. During the 4-year follow-up period the subjects' biopsychosocial situation remained almost unchanged, showing that, for most people, retirement is not a stressor of crucial importance or a life crisis. Of the variables relating to the initial survey, poor subjective physical health, self-assessed work disability, poor financial situation, change into a taciturn and timid individual in adolescence, the spouse's poor mental equilibrium, an excess of leisure time and general dissatisfaction with life were associated with subsequent mental disturbance as measured by use of the General Health Questionnaire. PMID- 2589094 TI - Dimensional approach to infantile autism in mentally retarded adults. AB - By use of latent trait models, a 7-item autism rating scale was established, based on the Medical Research Council's Schedule of Handicaps, Behaviours and Skills. Data from a community-based sample of 302 mentally retarded adults were assigning good internal validity to the autism scale, and revealing a distribution of symptoms consistent with dimensional, rather than categorical, distribution of infantile autism. A total of 23 (7.6%) of the sample were earlier diagnosed as suffering from infantile autism. Using this clinical diagnosis as a reference, the autism rating scale, with a cut-off point at greater than or equal to 2, established diagnoses with a sensitivity of 0.83 and specificity of 0.89. PMID- 2589095 TI - Sex difference in prevalence of minor psychiatric morbidity: a social epidemiological study in Taiwan. AB - The female excess in prevalence of minor psychiatric morbidity (MPM) evident in a community study in Taiwan (n = 1023) was further investigated in terms of demographic variables, socioenvironmental risk factors and psychosocial stresses. It was suggested that a stronger effect of chronic psychosocial stressors accounted for the higher prevalence of MPM in women. Further analysis has revealed a longer mean duration of MPM in women and an incidence ratio close to unity between the sexes. These retrospective findings were further examined in a small one-year prospective outcome study; a poorer outcome was found among older subjects and female subjects. It is suggested that more females have MPM because chronic psychosocial stressors more adversely affect the course of such morbidity. These results are discussed in a cross-cultural context. PMID- 2589096 TI - Patients in child and adolescent psychiatric care: psychopathology and background factors. AB - All 142 consecutive patients born between January 1, 1947 and February 28, 1949 who were cared for at the Department of Child and Adolescent Psychiatry at General Hospital in Uppsala are described. The patients' symptoms, family situation, early development, CNS dysfunction and social situation are presented. The negative factors were numerous: 78% of patients had some form of family affliction, 60% had minimal brain dysfunction (MBD) factors which, while not associated with a clinical diagnosis of MBD, included hyperactivity, motor handicap, reading and writing difficulties, poor fine muscle activity and pathological EEG, and 58% had negative factors in their home environment. The majority were judged as having been subjected to negative parental attitudes. When psychotic symptoms were present, there was a high prevalence of psychotic illness in the family. A negative social situation in the home environment was most common for maladjusted patients. The presence of MBD factors was associated with disturbances in the child's early development. Nevertheless, many background factors continually affected one another and contributed to the mental disorder. PMID- 2589097 TI - Absence of adult age differences in forgetting in the Brown-Peterson Task. AB - Despite some recent evidence to the contrary, no reliable age differences in proactive interference (PI) or retroactive interference (RI) were found in a cross-sectional study of adults aged 18-29 and 63-75. Individual memory span was used as the list length in the Brown-Peterson Task in order to achieve stimulus equivalence of memory loads across individuals and age groups. Data from rehearsers were excluded from the analyses in order to isolate age differences in passive forgetting processes from those in rehearsal. PI was manipulated by presenting categorized or uncategorized memory lists. RI was manipulated, holding distractor task difficulty constant, by using words or tones in a signal detection distractor task. It is concluded that age differences are minimal to nonexistent in passive RI-related processes such as decay and perturbation and in passive PI-related processes such as set effects in semantic encoding. PMID- 2589098 TI - Effects of location and form cuing on the allocation of attention in the visual field. AB - Two experiments were conducted which tested the effect of two different types of cues on the allocation of attention in the visual field. Subjects responded to a target appearing either 6.5 degrees to the right or to the left of fixation in a field filled with small randomly positioned line segments. The target form was either a circle or diamond in which a horizontal or vertical line segment was positioned. Subjects made a speeded discrimination response on the basis of the orientation of this line segment. In the first experiment, there was always one target at each trial. In the second experiment, both circle and diamond were presented left or right of fixation simultaneously whereby the line segment only appeared in one of the forms. In different conditions, the most likely target location (left or right) and form (circle or diamond) were cued. Control conditions served as a baseline for determining costs and benefits. Reaction time measures showed that the validity of the location cue resulted in both costs and benefits, whereas the validity of the form cue had no such effects. The results cannot be reconciled with the claim of zoom lens theories that spatial attention can switch between different modes of operations. They are also at odds with theories that claim that attention has no spatial locus. The results are consistent with a simple spotlight theory in which spatial attention involves selecting a particular restricted area of the visual field for which the perceptual efficiency is enhanced. PMID- 2589099 TI - Suicide and the attempted suicide: an international perspective. AB - This article reviews the scope of suicide and attempted suicide as public health problems from an international perspective. Socio-demographic trends are analyzed and explanatory theories for international differences proposed. Suicide and attempted suicide can be prevented, but the development and evaluation of effective large-scale prevention programs is still in its infancy. Inadequacies in current programs across the world has promoted the establishment of national Task Forces on Suicide Prevention in the United States, Canada and The Netherlands, as well as a WHO strategy on suicide prevention. These groups have formulated comprehensive strategies for the prevention of suicide. The main components of these strategies are: Design and implementation of national research programs; The improvement of services; The provision of information and training on suicide prevention to relevant professional groups, organizations and the general public; and Formulation of strategies and techniques to deal with special risk groups. The added recommendations are seen as important steps in translating a comprehensive national plan to prevent suicide into clinical and research programs that can be effectively implemented to prevent these tragedies around the world. PMID- 2589100 TI - Suicide prevention and antidepressants. Proceedings of a symposium of the 15th meeting of the International Association for Suicide Prevention. Brussels, June 1989. PMID- 2589101 TI - Why do fatal overdose rates vary between antidepressants? AB - Age specific death rates for poisoning with different antidepressant drugs, based on mortality statistics and the numbers of prescriptions dispensed, were calculated for England and Wales 1979-1985. There are marked variations in mortality associated with different drugs; the highest rates are found with amitriptyline and dothiepin whereas the lowest were associated with mianserin and clomipramine. For all drugs considered, the calculated mortality rates for the over 65 year olds, though still substantial, were lower than those in patients under 65 years of age, probably because of a diminished detection rate of poisoning in this older age group. A high proportion of the fatal overdoses implicating amitriptyline and dothiepin involved more than one substance. The rank order of mortality rates from antidepressants was identical in the different age groups. The implications of these findings are discussed. It is concluded that the variations in mortality rates are mostly due to variations in the inherent toxicity of the drugs (particularly their cardiovascular effects) and only in part due to possible differences in compliance. It is suggested that when antidepressant drugs are prescribed, the risk of death from overdose should be taken into account. Tricyclic drugs, particularly amitriptyline, dothiepin, doxepin, trimipramine and maprotiline, should be avoided in patients at risk of suicide, whatever the age of the patient. PMID- 2589102 TI - A fatal toxicity index for antidepressant poisoning. AB - Since depressed patients are liable to attempt suicide by self-poisoning, fatal poisoning from overdose is an important part of the overall assessment of any antidepressant drug. Because prescription figures for drugs are available in Britain, a Fatal Toxicity Index can be calculated in terms of deaths (from national mortality data) per million National Health Service prescriptions. This was carried out for the years 1975-1984 (Cassidy and Henry 1987), and has since been updated. The older tricyclic antidepressants as a group had a higher Fatal Toxicity Index than the mean for this drugs studied. Monoamine oxidase inhibitors had intermediate toxicity, and newer drugs introduced since 1973 had lower toxicity than the mean figure for all drugs, which was 34.9 deaths per million prescriptions. If drugs are equally effective clinically, serious consideration should be given to prescribing antidepressants with a lower fatal toxicity as a contribution to suicide prevention. PMID- 2589103 TI - Why do amitriptyline and dothiepin appear to be so dangerous in overdose? AB - Data from different analyses of reported deaths from overdose with antidepressants in the U.K. reveal that amitriptyline and dothiepin are the antidepressants most likely to be associated with death from overdose. All widely used tricyclic antidepressants (TCAs) except clomipramine and lofepramine appear to be dangerous in overdose, whereas the newer antidepressants such as mianserin, trazodone, viloxazine and the TCA lofepramine appear to be relatively safe. The toxicity of amitriptyline and dothiepin appears to be greater than all antidepressants including other TCAs and it is important to try to understand why. A number of explanations will be considered: 1. Dothiepin and amitriptyline may be inherently more toxic than other TCAs. 2. Dothiepin and amitriptyline may induce suicide more than other antidepressants. It is assumed that antidepressants are neutral with regard to inducing suicide but this may not be true. There is, for example, evidence that alprazolam and other benzodiazepines induce suicidal behaviour. 3. Amitriptyline and dothiepin are often presented in subtherapeutic and ineffective doses and it is possible that increased suicides may result from inadequately treated depression. 4. There may be a selective overreporting of deaths with amitriptyline and dothiepin. 5. Amitriptyline and prothiaden may be selectively given to the suicide prone on the mistaken assumption that they are safe. PMID- 2589105 TI - Norwegian data on death due to overdose of antidepressants. AB - The number of suicides in Norway has doubled during the last two decades, as has also the number of suicides by intoxication. Data are presented which demonstrate that while barbiturates make out a strongly decreasing percentage of the intoxications, the antidepressants make out a definite increasing percentage. The tricyclic antidepressants make out the bulk. There is a strong need for effective antidepressants with less toxicity than the commonly used tricyclic antidepressants. PMID- 2589104 TI - Fatal poisonings with antidepressants in Finland 1985-1987. AB - In Finland the majority of the users of antidepressants are women and old age people. In the 80's the number of fatal poisonings has increased. During the years 1985-1987 58% of these poisonings were women who belonged to the younger age group of the users. The older tricyclic drugs are known to be more toxic, at least in overdose, than the newer antidepressants especially when they are compared to mianserin. Of the latter, however, lately more serious side effects have been reported. For this reason the use of the different kinds of antidepressants in Finland had changed: the sales of doxepin and amitriptyline have increased and those of maprotiline and mianserin have decreased. To study the role of antidepressants in sudden and unexpected deaths the fatality ratio (defined as fatalities divided by defined daily doses per 1000 inhabitants/day) was calculated for four most prescribed antidepressants. As to the sales, amitriptyline has to be considered to be the leading antidepressant followed by doxepin, mianserin and maprotiline. As a detection in the forensic toxicological screening the sales related ratios showed that maprotiline was most commonly found followed by doxepin, amitriptyline and mianserin. When an antidepressant was the cause of death the fatality ratio was highest for doxepin (6.4) followed by maprotiline (4.3), amitriptyline (4.0) and mianserin (1). In cases of established suicides the order was the same again.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589106 TI - Substances involved in fatal drug overdoses in Brisbane, 1979-1987. AB - Suicide rates may be reduced by decreasing the availability, cultural acceptance or lethality of certain methods of suicide. With these principles in mind fatal overdoses in Brisbane 1979-1987 were surveyed for substances involved. Psychotropic agents, especially barbiturates predominated. Chloral hydrate was far the most commonly implicated single compound. A case is put for curtailing the availability of barbiturates and chloral hydrate. This combined with increasing detection of depressed persons may lead to a further rise in overdoses involving antidepressants which as a group require reduction in their lethality. PMID- 2589108 TI - Is oxytocin present in platelets? AB - For arginine-vasopressin (AVP) it has been suggested that about 90% of the total amount present in peripheral blood is platelet-membrane bound. Oxytocin (OT) and AVP are nonapeptides which are similar in many respects. We investigated the possibility that OT might be found in platelet-rich plasma samples from patients undergoing ovarian super-stimulation for in-vitro fertilization purposes. These plasma samples were treated with acid repeated freezing/thawing and sonification in an attempt to solubilize or expose the possible bound OT. No differences between OT concentrations in platelet-rich or -poor plasma samples were found. We conclude that plasma OT is not bound or confined to platelets. PMID- 2589107 TI - Lack of predictive value of HbA1 for impaired glucose tolerance in polycystic ovary syndrome. AB - Twenty-seven women with polycystic ovary syndrome (PCO) and 17 control women had a 75 g oral glucose tolerance test (oGTT) performed. Although glucose tolerance was impaired in the obese (body mass index greater than 25 kg/m2) women with PCO, glycosylated hemoglobin (HbA1) concentrations did not exceed the normal upper limit (7.2%). In all 44 women, there was no correlation between HbA1 and fasting glucose (r = 0.082, p = 0.63) but there was a significant correlation between HbA1 and summed glucose levels through the oGTT (r = 0.389, p = 0.02). HbA1 measurement does not predict the presence of impaired glucose tolerance in women with PCO. PMID- 2589109 TI - Stimulus modality effects on transformations of conditioned enhancement and conditioned suppression in rats. AB - Unconditioned and conditioned effects of house-light offset and acoustic white noise on barpressing behavior maintained by intermittent food reinforcement were tested in male hooded rats. Presentations of these stimuli prior to their acquiring signal value initially tended to depress and then to enhance barpressing rate, but generally the rate of the on-going barpressing was lower during the light offset then during noise presentations. Subsequently, one stimulus was used to signal continuous food reinforcement, evoking conditioned enhancement, and the other to signal inescapable footshock eliciting conditioned suppression of barpressing. The enhancement was acquired more rapidly than the suppression, independent of the stimulus modality used. The stimulus modality effect emerged when the continuous food reinforcement was withdrawn, since enhancement elicited by light offset extinguished more rapidly than elicited by noise. The stimulus modality effect was stronger when the other stimulus continued to signal pain and was attenuated when conditioned suppression was also extinguished. During the next stage of the experiment, the signal values of the conditioned stimuli were reversed, resulting in easy transformation of conditioned suppression into conditioned enhancement and vice versa. The stimuli used and changes in their signal values exerted clear effects on the rate of barpressing during intertrial intervals and this, in turn, somewhat modulated the behavioral effects of the conditioned stimuli. These results indicate that unconditioned effects of the stimuli on the behavior interact with their properties acquired in the course of conditioning. PMID- 2589110 TI - Hippocampal rhythmical slow activity during instrumental responses with sexual reinforcement in male rats. AB - The hippocampal EEG activity was recorded in male rats during the response contingent reinforcement of a female. The instrumental response was a bar pressing on a fixed-ratio-10 reinforcement schedule. The frequency of bar pressing tends to increase during the succeeding copulatory series. The similar phenomenon was observed in the frequency of the hippocampal slow activity (RSA) accompanying the bar-pressing and the pursuit of the female. This tendency was most conspicuously present during the first copulatory series but became less evident during the following ones. PMID- 2589111 TI - Hemispheric differences in evoked potentials to faces and words. AB - Sixteen right-handed subjects (8 male and 8 female) were asked to compare two faces or two words successively presented at the centre of the visual field. The brain's electrical activity was recorded from the scalp at symmetrical points of the left and right occipital lobes (0(1) and 0(2)) and posterior temporal lobes (T5 and T6). The reference electrode was placed on the scalp vertex (Cz). A multi factor analysis of variance revealed significant hemispheric differences of the N243 and P406 amplitudes. For the N243 the opposite asymmetry was found for faces and words. For the face matching the N243 amplitude was higher in the right hemisphere, whereas for word matching it was higher in the left hemisphere. For the P406 the asymmetry was in the same direction both for faces and words, with higher amplitude in the left hemisphere. In the case of face matching the hemispheric difference in the P406 was more pronounced, due to a negative shift of the potential in the left hemisphere in the latency range of 200-1,500 ms. Functional asymmetry of the brain in face perception thus appears to be reflected in the brain's electrical activity. We conclude that differentiation in hemispheric functions takes place while encoding information about stimulus in short term memory. PMID- 2589112 TI - Effect of GABA muscimol and picrotoxin on electrical activity of the medial preoptic area in unanesthetized rats. AB - Intracranial cannula along with electrodes was stereotaxically implanted in medial preoptic area of male rats. The electrical activity of mPOA was recorded before and after microinjection of GABA (0.5 micrograms/02 microliters), muscimol (0.5 micrograms/0.2 microliter), picrotoxin (0.25 micrograms/0.2 microliter) and their respective controls. Generalized slowing with an increase in amplitude appeared with GABA and muscimol, while picrotoxin produced just the reverse, i.e. fast activity. Thus the mPOA seems to be vulnerable to GABAergic compounds and supports the diversity of physiological and behavioral functions. PMID- 2589113 TI - Effects of a weak diffuse-brain-stimulation on insomniacs with vibration syndrome. AB - To verify the efficacy of a weak diffuse-brain-stimulation (DBS) method that was specially devised by this research team, a weak DBS was administered to seven male inpatients, who had vibration syndrome due to a prolonged use of a vibratory tool and who were simultaneously complaining of insomnia. Sleep data obtained from the polygraphic recordings on the DBS-treated night were compared with those on the pseudo DBS-treated. As the result, this DBS method proved to be effective in improving patients' sleep initiation and/or maintenance, and also their subjective ratings on the quality of actual sleep. In conclusion, the present DBS was determined to produce a decrease in the sympathetic tone which is needed at the onset of sleep. PMID- 2589114 TI - The state of the frontal sinus after craniotomy. AB - In 39 patients, 24 male, 15 female, the frontal sinus was opened during a frontal, a bifrontal or a pterional trephination for neurosurgical treatment of trauma, tumours or aneurysms. In 25 out of 39 patients the frontal sinus subsequently was obliterated, in 11 out of 39 patients the apical half or 2/3 of the sinus were ablated and the remaining caudal part covered with a galea periosteal flap leaving the fronto-nasal duct intact. In 3 out of 39 patients, the periphery of the sinus was ablated and the remaining part covered. All patients were followed over a mean period of 2 years and had a final evaluation using CTs, X-rays, ultrasonography and a complete ENT examination. In 4 out of 25 obliteration was successful and complete, in 16 out of 25 there was a partial or complete re-aeration of the residual sinus and in 5 out of 25 the sinus was infected. In one out of eleven patients where the frontal sinus was bisected with preservation of the lower half, the basal part of the sinus was infected, in 10 out of 11 the residual sinus was aerated and draining well. In one out of three patients where the periphery of the sinus was ablated, there was infection, two of three sinuses were aerated. Evaluating the experience in these 39 patients and our recent experience, obliteration of the sinus with muscle is very unreliable and the use of bone wax is obsolete. Covering a bisected or peripherally opened sinus with fascia or a galea periosteal flap will yield a well aerated and draining sinus, provided the naso-frontal duct is intact. PMID- 2589115 TI - Recurrences in meningioma after surgery. AB - 123 cases of meningioma operated upon between 1975 and 1984 were reviewed. There were 13 cases of symptomatic tumour recurrence and 15 cases of tumour progression. Both, recurrence and progression of the tumour were seen twice as often in males. They were not related to any particular age group or site of origin. Recurrence was more common in the angioblastic type of meningioma. In the majority, progression of the tumour was seen within two years of the initial operation, while recurrence of the tumour was distributed evenly over time. PMID- 2589116 TI - Radical resection of superior sagittal sinus meningioma with venous interposition graft and reimplantation of the rolandic veins. Case report. AB - A case of a 48 year old women is reported in whom a haemangiopericytic meningioma involving the middle third of the superior sagittal sinus was radically excised. The sinus was replaced by a saphenous vein graft and the Rolandic veins were reinserted. During clamping of the sinus the patient was heparinized and hypothermia, hypotension and barbiturates were used to prevent swelling of the brain. The postoperative course was uncomplicated and patency of the graft was demonstrated 2 weeks after the operation by Doppler sonography performed through a midline burr hole. The technical details of the operation and the pertinent physiology of cerebral venous flow are discussed. PMID- 2589117 TI - Post-traumatic intradiploic pseudomeningocele in children. AB - Eight children with post-traumatic pseudomeningocele are reported. In this paper the mean age at the time of injury was one year and ten months. All of them gave a history of a fall from a height. In six patients the meningocele was located in the parieto-occipital region. The frontal bone was involved in one and the roof of the orbit in another. All these patients had localized progressive swelling of the skull associated with a bony defect. Four patients had a history of convulsion and three had hemiparesis. The meningocele was excised, the dural defect repaired and a cranioplasty was performed in all. Good recovery was observed in all of them. PMID- 2589118 TI - Microsurgical unilateral approaches for spinal tumour surgery: eight years' experience in 256 primary operated patients. AB - A series of 256 consecutive patients suffering from spinal tumours was studied with respect to the value of bilateral or unilateral surgical approaches. The case material included 152 extradural, 87 intradural, extramedullary and 17 intramedullary tumours. The cervical spinal cord was involved in 43, the thoracic in 152 and the lumbosacral region in 61 cases. Hemilaminectomy was chosen mainly for juxtamedullary tumours, while laminectomy was used for intramedullary tumours. No remarkable difference regarding the choice of approaches was found in extradural tumours. More than 60% of cervical or lumbosacral tumours were managed using unilateral procedures. A higher rate of surgical radicality but fewer complications, shorter stay in hospital and better early results were achieved using hemilaminectomy especially in patients with juxtamedullary tumours. From the observations it may be concluded that the results do not depend on the type of surgical approach but are closely related to the histology and location of tumours. Under the prerequisite of exact pre-operative definition of tumour location, unilateral approaches are advantageous for all kinds of spinal tumours especially for juxtamedullary benign tumours. PMID- 2589119 TI - Kissing spines: fact or fancy? AB - In the Neurosurgical Clinic in Groningen 64 patients underwent surgery between 1975 and 1985 for a clinical and radiological syndrome described by Baastrup in 1933 and called in the Anglo-saxon literature: "kissing spines". Because the results of the surgical treatment were disappointing we submitted these results to further analysis. PMID- 2589120 TI - Spinal dural arteriovenous malformations with perimedullary drainage. Indications and results of surgery in 30 cases. AB - 70 patients were treated for spinal dural arteriovenous fistula in the same centre, during a period of 10 years. Conus medullaris and cauda equina syndromes were observed in all patients as the clinical stereotyped presentation. Diagnosis was based on myelography in the first instance and then on angiography. 40 patients were treated by intravascular neuroradiological embolization, whereas the other 30 were operated on. Surgery was proposed because embolization was contraindicated (7 cases of hazardous catheterisation) of inefficient (23 cases = 38%). The results of the operative series are presented, and compared with those of embolization. Improvement was observed in 50% of the 20 patients with follow up, but a complete recovery to an asymptomatic state was never obtained. For the other patients (47%) complete stabilization of the disease could be obtained, whereas in one of the patients (3%), who was operated upon because of failure of embolization, surgery was also completely ineffectual. The long-term results of patients treated surgically are comparable with those patients efficiently embolized. 5 patients of the operative series were submitted to MRI before and after surgery: the results and the place of MRI are discussed. PMID- 2589122 TI - Cerebral circulation and metabolism in adults' moyamoya disease--PET study. AB - Regional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF), cerebral metabolic rate for oxygen (rCMRO2) and cerebral blood volume (rCBV) in nine cases of moyamoya disease in adults were studied with positron emission CT (PET) scan, using 15O steady-state methods. Three cases showed ischaemic symptoms and the other six cases showed haemorrhagic symptoms. PET scan was performed during the chronic stage. Control data were obtained from eight normal volunteers. Regional cerebral blood flow and other physiological parameters in cerebral gray matter, white matter and basal ganglia were compared with normal controls. All nine cases of Moyamoya disease showed decreased rCBF, though not significant, in cerebral gray matter, white matter and basal ganglia. Reduction of rCBF was significant in the cerebral cortex of six haemorrhagic cases. This significant decrease was considered to be due to diaschisis and also brain atrophy caused by the cerebral haemorrhage. There was a significant increase in rCBV in white matter of the both ischaemic and haemorrhagic cases. The calculated value of CBF/CBV is considered to be an index of perfusion pressure. This value was significantly decreased in all three regions, though rOEF was not significantly increased in moyamoya disease. Hence the cerebral circulation in adults with moyamoya disease appears to be characterized by a mild decrease in perfusion pressure and prolonged circulated time. PMID- 2589121 TI - Sequential changes of auditory brain stem responses in relation to intracranial and cerebral perfusion pressure and initiation of secondary brain stem damage. AB - The relationship of supratentorial intracranial pressure (ICP) and cerebral perfusion pressure (CCP) with serial changes in auditory evoked brain stem responses was investigated. Eighty-one patients without primary brain stem damage admitted to our emergency unit were studied. When ICP over 50 mm Hg persisted for 4 hours, the I-V interpeak latency was significantly prolonged. The threshold of this prolongation was 8 hours for the ICP over 45 mm Hg and 24 hours for that of over 40 mm Hg. The ICP of 35-40 mm Hg for 24 hours was the border zone. CCP did not show a significant relation with I-V interpeak latency changes. The loss of wave V was observed in a wide range of the ICP (30-147 mm Hg) and CPP (0-60 mm Hg). Wave III disappeared when the ICP exceeded 50 mm Hg. Wave I became undetectable with an ICP above 50 mm Hg or a CPP below 40 mm Hg. These results indicate that an increase of ICP over 40 mm Hg definitely initiates secondary brainstem dysfunction if it lasts for more than 24 hours and that the ICP should be reduced below this level, preferably below 35 mm Hg, to maintain brain function. The fact that both low CPP and high ICP were involved in the loss of wave I clearly shows that both ischaemia and displacement of the brain stem are the important pathophysiological factors for the disappearance of wave I. PMID- 2589123 TI - Relationship between CT attenuation changes and post-traumatic CSF-CKBB-activity after severe head injury in man. AB - In order to evaluate if it is practically possible to assess the volume of contused brain tissue from the CT pictures, a comparison has been carried out between the size of the cerebral contusion(s)--as estimated from the CT scans- and the post-traumatic CSF-CKBB activity, in a series of 29 patients with severe head injury. A clearance curve for the elimination of CKBB from the CSF was constructed. The relation between contusion volume and CSF-CKBB-activity was not statistically significant, while the relationships between contusion volume and outcome, and between CSF-CKBB, as estimated at 6 hours after from the clearance curve, and outcome, were. PMID- 2589124 TI - Ultrastructural changes of the basilar artery following experimental subarachnoid haemorrhage. A morphological study on the pathogenesis of delayed cerebral vasospasm. AB - Recent experimental studies have shown, that the endothelium of cerebral vessels undergoes significant changes after subarachnoid haemorrhage which may lead to biochemical changes at the endothelial surface with disturbance of the delicate homeostasis of vasodilating and vasoconstricting mechanisms which are thought to be responsible for preservation of the tones of the cerebral vasculature. Ultrastructural studies incorporating different forms of microscopic observations of the endothelium after SAH representing a prerequisite for further investigations on the pathogenesis of cerebral vasospasm are scarce. The experimental study was performed in order to investigate and define more precisely the pathomorphological changes at the endothelial surface of the basilar artery of dogs after experimental SAH. Two separate injections of autologous blood into the cisterna magna within 72 hours resulted in extensive angiographic narrowing of the diameter of the basilar artery of all animals. Histological studies of the basilar artery including light microscopic, transmission electron microscopic, scanning electron microscopic and freeze cracking microscopic examinations demonstrated severe pathomorphological changes at the endothelial surface. These consisted mainly of infolding and corrugation of the endothelium, disorientation and desquamation of endothelial cells as well as of vacuolation and ingrowth of fibrous tissue between the endothelial and muscular layer. No pathomorphological changes could be observed in the muscular layer. As the described post-haemorrhagic ultrastructural changes of the endothelium cerebral vessels in spasm are likely to represent the morphological basis of the delayed form of cerebral vasospasm future research on its pathogenesis should primarily focus on the structural and biochemical taking place at the endothelial surface of the cerebral vasculature after SAH. PMID- 2589125 TI - Neuro-rhinosurgical treatment of aesthesioneuroblastoma. AB - The results of a combined neuro-rhinosurgical procedure in eight cases of aesthesioneuroblastoma are presented. All patients were suffering from tumours in the advanced stage (stage C according to Kadish). Diagnosis was established by the clinical history, neuro-radiological imaging and by endoscopic endonasal biopsy. Contrary to most reports in the literature the authors performed a one step operative removal of the whole tumour mass by a combined transcranial transbasal approach alone. A second transfacial operation was unnecessary in all our cases. To the best of our knowledge only Loew (see Jakumeit 1971) already in the 1960ties used a comparable one step transcranial approach for tumour removal. The long-term survival rate in our patients is 50%, a result comparable to reported series in the literature. Mortality is due to early recurrences and metastases within a few months after the initial treatment including post operative irradiation. Four patients are living without evidence of tumour recurrence 1.5 to 5 years after treatment. The authors surgical technique is presented in detail and compared with the results of other treatment modalities. PMID- 2589126 TI - Efficacy of a minimal contact version of a multimodal smoking cessation program. AB - A five-week multimodal smoking cessation program was delivered in two formats: Weekly Contact Group meetings led by graduate student leaders versus a minimal contact By-Mail version consisting of weekly mailings of program materials. By Mail subjects also had access to a "hotline" number they could call with questions and problems. Of 43 smokers who began the Contact Group program, 37% were abstinent at one-year follow-ups; 41% of the 49 By-Mail subjects were abstinent at one year. These results suggest that cost effective minimal contact cessation programs can benefit the many smokers who are unwilling or unable to visit cessation clinics. PMID- 2589127 TI - Carbon monoxide assessment of smoking in chronic obstructive pulmonary disease. AB - Chronic Obstructive Pulmonary Disease (COPD) is a major, often fatal, drain on health-care resources. Most cases of COPD result from Tobacco Dependence, and smoking cessation slows COPD's progression. But there is very little information on treating Tobacco Dependence in COPD patients. In preparation for clinical trials using monetary payments to motivate reduced smoking, as assessed by breath carbon monoxide (CO) levels in COPD patients, we have addressed three issues. First, surveying 182 advanced COPD patients, we found that CO levels above 8 parts per million (ppm) were strongly associated with a self-report of current smoking, and that CO levels correlated neither with COPD severity, nor with age: about one-third of these patients were currently smoking. Second, among 12 still smoking COPD patients serially observed for 8 h. CO half-life averaged about 6.5 h. Third, 8 patients reinforced with lottery tickets for CO reductions significantly reduced CO levels during 2 test weeks, mainly by deferring smoking before scheduled CO measurements. PMID- 2589128 TI - Emotional and somatic consequences of binge episodes. AB - The present study investigated emotional and somatic consequences of the daily eating episodes of 19 bulimics, 15 bingers, and 20 normal control subjects. For 1 week, subjects rated 21 emotional and somatic states immediately following all eating episodes and 1 h later. Results indicated that bulimics and bingers reported significantly greater negative and somatic consequences immediately following their binge episodes than normal eaters following all of their eating episodes. For both groups, these negative emotional consequences persisted over time. Following nonbinge episodes, only bulimics reported experiencing significantly greater negative emotions than normal controls. Comparisons of the binge and nonbinge episodes of the bulimics and bingers indicated that binge episodes are followed by greater immediate and delayed negative and somatic consequences than nonbinge episodes. Furthermore, the positive emotions that occur immediately after a binge significantly decrease in intensity within 90 min after the episode. Theoretical and clinical implications of these findings are discussed. PMID- 2589129 TI - Biases in relapse attributions made by alcoholics and their wives. AB - Although numerous studies have investigated the relapse attributions of alcoholics, few have considered the biases inherent in such attributions. Two sources of bias were investigated in the relapse attributions of 26 alcoholic men and their wives: the passage of time and actor-observer perspective. As predicted: (a) Wives made more dispositional attributions than their husbands (an actor-observer difference); (b) the attributions of the husbands showed a dispositional shift over time, while their wives' attributions showed no temporal effects; and (c) attributional concordance within couples increased over time. Several explanations for these results were considered and implications for couples therapy with recovering alcoholics and their spouses were discussed. PMID- 2589130 TI - A study of factors associated with weight change in women who attempt smoking cessation. AB - This study investigated behavioral and attitudinal relationships over a 12-week time period in 48 women enrolled in a commercial smoking cessation program who were categorized as non-recidivists (NR), early recidivists (ER) and late recidivists (LR) to cigarette smoking. NR had significantly higher weight gains (F = 6.70), significantly higher levels of physical activity (F = 6.42), and significantly less concern of postsmoking cessation weight gain (F = 5.08) than either two groups of recidivists, (p less than or equal to .05). Other findings, although not significant, were that NR exhibited lower caloric intake and more frequent snacking behaviors than either ER or LR. These results indicate an overall stronger commitment to more positive health behaviors in the NR than those who returned to cigarette smoking. PMID- 2589131 TI - Relationship between alcohol expectancies and length of abstinence among Alcoholics Anonymous members. AB - Previous research has demonstrated a consistent relationship between alcohol expectancies (i.e., cognitive expectancies concerning the reinforcing effects of alcohol) and alcohol consumption patterns. To date, no study has examined the expectancies of recovering alcoholics who have attained extended abstinence. One hundred and fourteen Alcoholics Anonymous members were examined. Significant negative correlations were found between the recovering alcoholic's length of sobriety and many of the alcohol expectancy scales. In addition, 11 items from the Customary Drinking Record-Revised and 2 items from the Demographic Data Sheet were factor analyzed resulting in the retention of two factors, Quality of Life and Desire to Drink. These factors seemed to be tapping important dimensions in the alcoholic's recovery. Two alcohol expectancy scales were found to be significantly predictive of the Desire to Drink and Quality of Life factors that were used as criteria in multiple regression equations. PMID- 2589132 TI - Familial and personality correlates of alcohol-related problems. AB - Family history of alcohol abuse and personality characteristics measured by the MacAndrew Alcoholism Scale (MAC), two factors that have been associated with the development and expression of alcoholism in clinical populations, were examined in a nonclinical, putatively normal sample. Analyses revealed that although family history positive subjects (FHP) drank as much and as often as family history negative subjects (FHN), the FHP subjects experienced significantly more alcohol-related problems. Consistent with previous findings with clinical samples, both family history of alcohol abuse and the MAC were associated with increased alcohol-related problems in a nonclinical sample. Furthermore, family history of alcohol abuse and the MAC appeared to be measuring relatively independent factors associated with alcohol abuse. PMID- 2589133 TI - Alcohol and drug use among homosexual men and women: epidemiology and population characteristics. AB - Homosexual men and women have been described as at high risk for alcohol and drug abuse, due to psychosocial variables such as stress levels or the cultural importance of bar settings. However, there are few actual data in this regard. This paper presents the findings of a large (n = 3400) survey of a homosexual population regarding population characteristics and patterns of alcohol and drug use. Psychosocial variables that may account for substance use patterns both generally and in this population are discussed in an accompanying paper. Substantially higher proportions of the homosexual sample used alcohol, marijuana, or cocaine than was the case in the general population. Contrary to other reports, this was not accompanied by higher rates of heavy use, although homosexuals did show higher rates of alcohol problems. In the general population women consume less drugs and alcohol than do men, and substance use substantially declines with age. Neither of these patterns were found for the homosexual sample, thus creating overall higher rates of substance abuse. This may reflect differences between homosexuals and the general population in their adherence to sex-role stereotypes and age-related social role changes, as well as culturally specific stressors and vulnerability to substance use. PMID- 2589134 TI - Psychosocial and cultural factors in alcohol and drug abuse: an analysis of a homosexual community. AB - Homosexual men and women may be at risk for alcohol and drug abuse due to psychosocial variables such as drinking styles, stress, or the cultural importance of bars. The study of psychosocial variables in homosexual culture may help us understand how they operate generally. This paper describes the findings of a large (n = 3400) survey of homosexual population. The core hypothesis was that stress and other psychosocial variables have their primary effects among people made vulnerable to substance abuse by individual expectancies and/or cultural values. Tension reduction expectancies of alcohol effects had substantial effects on alcohol and drug abuse, as did the use of bars as a social resource, a vulnerability variable more specific to urban homosexual culture. Further, stress affected alcohol-drug problems only among people who were "vulnerable" via expectancies and values, and both high risk styles of substance use and simple consumption levels had much stronger effects on problems among vulnerable respondents, thus supporting the stress-vulnerability perspective. Individual differences in social role status was related to alcohol and drug problems, and may explain differences between homosexual and general populations. PMID- 2589135 TI - Psychopathy, aggression, and family history in male veteran substance abuse patients: a factor analytic study. AB - Forty-one male patients consecutively admitted to an inpatient VA substance abuse program completed the Psychopathic States Inventory, the Buss-Durkee Hostility Inventory, and the WAIS. Multiple significant intercorrelations between scale scores were noted, prompting a factor analysis to identify constructs to explain these correlations. Four orthogonal factors were isolated: Factor I- impulsivity/narcissism/sociopathy; Factor II--assaultive aggression; Factor III- irritative aggression; Factor IV--IQ. Patient factor scores were distributed independent from family history of alcohol or other substance abuse among first degree relatives. Family history status did not discriminate onset of substance abuse, "pure" alcohol abuse versus mixed substance abuse, educational attainment, or socioeconomic status. These factors may have further utility in investigating the relationship between psychopathy, aggression, and substance abuse. PMID- 2589136 TI - Paced puffing as a method for administering fixed doses of nicotine. AB - Smokers' ability to regulate nicotine intake by varying topographical parameters such as depth of inhalation and number of puffs makes it difficult to administer standardized doses of nicotine as delivered from smoking. A number of studies have claimed to control these parameters without confirming the effectiveness of such procedures by measures of plasma nicotine. The purpose of the present study was to determine whether specifying onset and duration of each puff would result in accurate dosing. Plasma nicotine boosts for five "paced puffers" were compared across two sessions and with similar data for five "free smokers." Neither between-subject consistency nor within-subject reproducibility was improved by this paced puffing procedure, despite apparent topographical control. PMID- 2589138 TI - Exercise suppresses heritability estimates for obesity in Mexican-American families. AB - In multivariate analysis, suppressor variables attenuate the true relationship between predictor and outcome variables. Although suppressor variables relationships were described more than 45 years ago, few examples have been reported in the health care literature. We studied the correspondence between body mass in 111 Mexican-American families. Estimates of exercise suppressed the correlation between body mass for some dyads within these families. We concluded that the suppressor variable relationship may cause underestimates of heritability in multivariate studies. PMID- 2589137 TI - Effect of tobacco withdrawal on sustained attention. AB - Sixteen smokers completed a sustained attention task, were randomly assigned to either continue smoking or abstain for 24 h, and were retested. Eight nonsmokers served as a control group. Abstinence increased the variability in responding. Abstinence also appeared to impair the ability to inhibit responding. Abstinence did not potentiate fatigue during the task. These results are consistent with reports that tobacco withdrawal increases difficulty concentrating and impatience but does not increase fatigue. PMID- 2589139 TI - Validity, reliability, and factor structure of the Anorectic Cognitions Questionnaire. AB - Several authors have hypothesized cognitive distortion as central to the psychopathology of anorexia nervosa and bulimia. However, there have been few investigations of these hypotheses. Equally as important, psychometrically sound devices for assessing these cognitions are notably lacking. The purpose of this investigation is to examine the psychometric characteristics of the Anorectic Cognitions Questionnaire (MAC). This study reports on initial item development, initial concurrent validity, factor structure, initial item refinement, and internal consistency. Results indicated that the MAC has good concurrent validity, three theoretically defined factors were empirically supported, and the scale is internally consistent. PMID- 2589140 TI - Issues in geriatric psychiatry. PMID- 2589141 TI - Education and training in geriatric psychiatry. PMID- 2589142 TI - Toward greater understanding of depression in deaf individuals. AB - We compared the prevalence of depressive symptoms among deaf and hearing college students and examined the relationships among depressive symptoms, personality characteristics, and perceived parental attitudes and behaviors in these two groups. Measures were revised to meet the language needs of the deaf subjects. Mild levels of depressive symptoms were more prevalent in the deaf than in the hearing students, but more severe depression was not. In both groups, depressive symptoms were associated with perceptions of lower maternal care and higher maternal over-protection. Deaf and hearing subjects did not differ on these perceived maternal characteristics. Depressive symptoms were associated with socially dependent personality characteristics in the hearing sample only. We discuss the implications of the findings for the role of personality development in depression in deaf individuals. PMID- 2589143 TI - The prevalence and characteristics of tinnitus with profound sensori-neural hearing impairment. AB - This study investigated the prevalence and characteristics of tinnitus in 331 children with profound hearing impairment. Tinnitus implies an auditory perception of internal origin (noise) rarely heard by others. In view of the medical significance of tinnitus in adults, it is reasonable to believe that the same in children may have significant implications for medical and rehabilitative management. In the current study, one out of every three children had tinnitus. This finding raises some professional challenges regarding the effect of tinnitus on the affected children's behavior and performance in school. PMID- 2589144 TI - The use of cumulative cloze to investigate contextual build-up in deaf and hearing readers. AB - This study finds no significant differences between deaf and hearing readers' sensitivity to contextual build-up as evaluated in a cumulative cloze exercise measured by a 2 X 5 X 2 factorial design using readers at the eighth, tenth and twelfth grade levels. Differences favoring hearing readers have been documented at the fourth and sixth grade levels. Results from the current study and its antecedents indicate that readers in both groups predict meaning more accurately when given passage-level rather than sentence-level contextual constraints. Additionally, both groups predict meaning more accurately and their predictions become more semantically and grammatically acceptable as the amount of contextual information increases. Deaf readers, however, tend to abandon correct choices more often than do hearing readers. PMID- 2589145 TI - Positive justice reasoning in deaf and hearing children before and after exposure to cognitive conflict. AB - The development of positive justice reasoning in profoundly deaf, signing Australian 7- to 12-year-olds and hearing children was compared. Reactions to cognitive conflict were also assessed. The performance of those deaf children whose signed English skills were adequate to give detailed justifications for reward allocation was examined separately. The deaf children were delayed relative to hearing children in number and liquid conservation, but equally mature in justice reasoning. Spontaneous conflicts with signing peers over sharing possessions conceivably could be responsible for the fluently signing deaf children's development of positive justice reasoning on pace with their normally-hearing counterparts. Experimentally-induced conflict resulted in progress for the hearing but not the deaf children. Results are discussed in relation to factors that promote deaf children's tolerance for ambiguity (Brice, 1985) and impede their resolution of cognitive conflict (Liben, 1978). PMID- 2589146 TI - Use of the Kaufman-Assessment Battery for Children with the hearing impaired. AB - The Kaufman-Assessment Battery for Children (K-ABC), a measure of cognitive functioning, was administered to 26 male and 24 female hearing-impaired elementary school students to determine its appropriateness for hearing-impaired children. The Wechsler Intelligence Scale for Children-Revised (WISC-R) also was administered. Scores for the present hearing-impaired sample on the K-ABC were compared with the normative group and were correlated with the WISC-R and standard achievement test scores. Results showed that both the Simultaneous Processing Scale and the Nonverbal Scale seemed appropriate for hearing-impaired children, whose scores were similar to those of the test's normative sample. Scores on the K-ABC also correlated highly with scores from the WISC-R. The Sequential Processing Scale was more problematic and not as useful. The K-ABC was significantly related to school achievement. Difficulties in the administration of the instrument with hearing-impaired children also are discussed. PMID- 2589147 TI - Traumatic pancreatic transection. AB - Pancreatic contusion or transection may result from blunt or penetrating trauma. Considerable morbidity and mortality may occur if the injury is not diagnosed and treated promptly. Clinical diagnosis of pancreatic injury due to blunt trauma is difficult, because the symptoms are often delayed and nonspecific. Computed tomographic scanning is the method of choice for the diagnosis of pancreatic injury, although abdominal ultrasound may be particularly useful in children. Endoscopic retrograde cholangiopancreatography is used to assess ductal integrity. PMID- 2589148 TI - Opportunistic infections are major factor in HIV mortality. PMID- 2589149 TI - APHA adopts policy statements on abortion and on HIV safety precautions. PMID- 2589150 TI - Tracking tinnitus hunches. PMID- 2589151 TI - Improving Pap smears. PMID- 2589152 TI - Bone marrow sampling. AB - Bone marrow sampling may be indicated in the evaluation of iron metabolism, fever of unknown origin, anemia, leukocytosis and other hematologic abnormalities. The commonly accepted means of marrow sampling are needle aspiration and needle biopsy. The preferred site for obtaining the sample is the iliac crest. Contraindications to the procedure include infection or previous radiation therapy at the sample site, poor patient cooperation and major coagulation defects. The assistance of a skilled technician, use of a prepackaged tray, thorough patient education, use of local anesthesia and attention to aseptic technique help simplify bone marrow sampling. PMID- 2589153 TI - Late follow-up of 781 patients undergoing percutaneous transluminal coronary angioplasty or coronary artery bypass grafting for an isolated obstruction in the left anterior descending coronary artery. AB - Seven hundred eighty-one patients with isolated left anterior descending coronary atherosclerosis treated with either coronary artery bypass grafting or percutaneous transluminal coronary angioplasty between January 1980 and December 1984 were studied to determine late survival and event-free survival. Follow-up was complete in 775 patients (99.4%). Actuarial survival at 5 years was 98% for surgical patients and 95% for angioplasty patients (p = 0.02). Five-year event free survival (freedom from myocardial infarction, bypass grafting, angioplasty, and death) was 93% for surgical patients and 62% for angioplasty patients. This study suggests that the higher initial cost and complexity of bypass surgery may be justified by superior long-term results. PMID- 2589155 TI - The mechanism and significance of ventricularization of intracoronary pressure during coronary angiography. AB - Ventricularization of pressure during coronary angiography has been said to identify the presence of left main coronary artery disease, but the hemodynamic features and the mechanism of this process have not been studied. Twenty consecutive patients with ventricularization were identified prospectively in our laboratory. Four patients had a discrete ostial left main stenosis and 16 patients had stenosis of the entire length of the left main coronary artery. The degree of pressure drop upon cannulation of the diseased left main coronary artery was highly variable; the systolic pressure decreased by 9 to 94 mm Hg, and the diastolic pressure decreased by 6 to 60 mm Hg. The morphology of the ventricularized pressure was distinct. It had a presystolic deflection resembling an a wave. The upstroke of this waveform was slower and the downstroke was steeper than that of the aortic pressure. An identical waveform was observed in dogs after partial occlusion of the left main coronary artery with a balloon tipped catheter. The waveform of the so-called ventricularized pressure is derived from the aortic pressure, which is altered by its transmission across the left main coronary stenosis. The appearance of ventricularization is an important clue to the presence of left main coronary artery disease. PMID- 2589154 TI - Emergency angioplasty in acute anterior myocardial infarction. AB - Ninety-three patients with acute anterior myocardial infarction were treated with emergency percutaneous transluminal coronary angioplasty (PTCA). All were found to have a high-grade obstruction in the left anterior descending (LAD) vessel or the bypass graft to this vessel; 64 patients had a total occlusion. A completely successful PTCA, defined as a residual lesion of less than or equal to 50%, was achieved in 73 (78%) patients. A partially successful PTCA, with a residual lesion of 51% to 99%, was achieved in 12 (13%) patients. PTCA was unsuccessful in eight (9%) patients. Hospital mortality was 14%. Three parameters viewed separately each predicted hospital mortality: presence of shock, a proximal location of the LAD vessel occlusion, and the residual stenosis after PTCA. Reocclusion was found in only 11% of patients but 34% had evidence of restenosis on restudy. PMID- 2589156 TI - Transmural gradients of coronary flow reserve with physiologically and morphometrically defined stenoses in dogs. AB - Coronary angiography permits identification of stenotic lesions but underestimates their severity and does not provide information regarding their physiologic significance. Evaluation of coronary flow reserve by means of selective coronary artery Doppler flow catheters or quantitative arteriography has been proposed to obtain this information. However, these techniques may not accurately reflect transmural gradients in flow. We evaluated the relationship between flow reserve defined with an epicardial Doppler flow probe and the transmural gradient of flow measured with radiolabeled microspheres in 21 dogs with graded stenoses and correlated results with coronary artery geometry measured morphometrically. Four groups of dogs were studied. In five control dogs without stenosis, reactive hyperemia after 20 seconds of complete coronary occlusion was 4.5 +/- 1.5 (mean +/- SD) times resting flow with an endocardial/epicardial flow ratio at peak flow of 1.0 +/- 0.2. When reactive hyperemia was blunted (without affecting resting flow) by 50% (n = 6), 75% (n = 5), or was abolished completely (n = 5) by coronary stenosis, the endocardial/epicardial flow ratio at peak flow was 1.0 +/- 0.3, 0.7 +/- 0.2, and 0.5 +/- 0.1, respectively. Cross-sectional area of the stenosed segment was reduced by 85.6 +/- 3.5%, 91.1 +/- 2.2%, and 92.8 +/- 4.3% in these groups, respectively. Thus in dogs with stenoses exceeding 86% of the cross-sectional area, endocardial flow reserve is compromised disproportionately compared with epicardial flow reserve, suggesting that clinical measurements of coronary flow reserve may underestimate the physiologic significance of coronary stenoses. PMID- 2589157 TI - Clinical and hemodynamic course of infants and children with anomalous left coronary artery. AB - The clinical history of all 17 patients with anomalous left coronary artery presenting over the last 20 years was studied, with special emphasis on those who underwent reimplantation of the anomalous coronary artery into the aorta, a procedure that became our "treatment of choice" during this period. These patients were also evaluated for ventricular performance, residual mitral regurgitation, and wall integrity. Early in our experience with reimplantation, two patients died while we waited for them to achieve a more favorable size for surgery. Eight of nine survived reimplantation; three of these were under 1 year of age when operated upon. One of these eight patients has required additional mitral valvuloplasty, but all are doing well clinically up to 12 years after operation. Preoperative left ventricular ejection fraction of 0.37 +/- 0.16 increased to 0.67 +/- 0.07 (p less than 0.001) by 1 year after surgery, despite ventricular wall abnormalities in four patients. Thus reimplantation of the anomalous left coronary artery should be undertaken upon diagnosis, since surgery can be performed successfully in infancy, with resultant improvement in ventricular function and an adequate clinical condition for at least 12 years. PMID- 2589158 TI - The spectrum of death after myocardial infarction: a necropsy study. AB - To determine the relative frequency of the causes of death in the acute (less than 24 hours), early (24 hours to 3 weeks), and chronic (greater than 3 weeks) phases of myocardial infarction, data from all autopsies performed at a university hospital during a 56-month period were reviewed. Autopsies were performed in 56% of in-hospital deaths and 27% of patients dead on arrival in the emergency room (out-of-hospital deaths). In 271 cases of suspected cardiac death, a myocardial infarction of any age was identified. Death had occurred in the acute phase of a first infarction in 19 patients and was most frequently due to pump failure (37%) followed by cardiac rupture (26%) and arrhythmias (21%). Death had occurred 24 hours to 3 weeks after a first infarction in 80 patients and was most frequently due to pump failure (44%), rupture (27%), and arrhythmias (16%). Recurrent acute infarction was found in 32% of patients whose deaths were due to arrhythmias or pump failure and in 19% of those whose deaths were due to rupture. Death had occurred greater than 3 weeks after a first infarction in 172 patients. In 132 (77%) of these patients death was due to a complication of a new acute or recent infarction. Myocardial rupture was a less frequent cause of death in patients with recurrent infarction (8%) than in those dying in the acute or early phase after their first infarction (27%, p = 0.0009). A primary arrhythmia in the absence of recurrent infarction or ischemia accounted for only 14% of out-of hospital deaths late after an infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589159 TI - Anatomic findings in acute papillary muscle necrosis. AB - To investigate the consequences of acute papillary muscle necrosis of the left ventricle, 25 cases from a total of 133 autopsies of acute myocardial infarction were studied. Cardiac hypertrophy was found in 84%. The anterior papillary muscle was involved in four cases, the posterior in 13, and both muscles in eight. Left ventricular subendocardial infarction was found in 32% of cases. The size of left ventricular necrosis ranged from 11% to 75% of the left ventricular mass. Associated right ventricular infarction was observed in 68%. There were 19 cases of cardiogenic shock, four cases of pulmonary edema, and two cases of sudden death. We conclude that papillary muscle necrosis is usually associated with cardiac hypertrophy, posterior necrosis of both ventricles, and subendocardial infarction. Acute mitral regurgitation is probably an important contributing factor to clinical impairment and death, mostly in cases of small necrosis. PMID- 2589160 TI - Exercise-induced alterations of signal-averaged electrocardiograms in marathon runners. AB - Late potentials have been shown to predict malignant ventricular arrhythmias and sudden cardiac death. To determine whether prolonged, strenuous activity is associated with the development of ventricular late potentials, signal-averaged electrocardiography was performed on 30 marathon runners before, immediately after, and during a recovery period at least 1 week after they had a 26.2-mile race. The filtered QRS duration decreased immediately after the marathon to 94.4 +/- 10.0 msec from baseline values of 97.3 +/- 10.1 msec (p less than 0.005). Root mean square energy in the terminal 40 msec of the QRS complex increased immediately after the race from 60.4 +/- 35.6 uV to 71.0 +/- 41.7 uV (P less than 0.5). The duration of signals less than 40 uV in the terminal QRS were not appreciably altered. At the 1-week follow-up study, all parameters closely approximated the baseline values. No runner had a late potential after running the race. The one runner with a late potential at baseline had normal parameters immediately after the race. We conclude that signal-averaged ECG parameters are improved after a marathon is run, and the risk of an arrhythmic sudden death in adult runners without organic heart disease would seem to be low. PMID- 2589161 TI - Ventricular fibrillation without apparent heart disease: description of six cases. AB - Since 1977, six patients (five males and one female), aged 14 to 35 years, resuscitated from ventricular fibrillation, were referred to our department for detailed evaluation, after exclusion of major cardiac pathologic conditions. Four patients had a family history of heart disease. Basic ECGs showed sinus rhythm in all of them. PR interval was prolonged in one. Two patients had complete and one had incomplete right bundle branch block. One patient had inverted t waves in V1 3 and late potentials. Three had an upsloping ST-T segment elevation in V1-2. The cardiothoracic index was less than 0.5 in five and 0.50 in one. In one of the five patients studied, the clinical episode of ventricular fibrillation was reproduced by stimulation of the right ventricular outflow tract during electrophysiologic study. Results of cross-sectional echocardiography and angiography showed predominantly structural and wall motion abnormalities of the right ventricle in five patients and slight wall motion abnormalities of the left ventricle in two. Two patients also had mitral and tricuspid valve prolapse. Coronary arteries were normal in all five patients examined. Results of endomyocardial biopsy showed no abnormalities in one patient, fibrosis in two, and fibrolipomatosis in one. Two patients died during follow-up: autopsy was performed in one and results showed right ventricular cardiomyopathy. Thus in five of these selected patients with apparent idiopathic ventricular fibrillation, some abnormalities, predominantly of the right ventricle, were documented only after detailed investigation; however, clinical history and some nonspecific ECG abnormalities were factors in the diagnostic procedure. PMID- 2589162 TI - Effects of diltiazem on phosphate metabolism in ischemic and reperfused myocardium using phosphorus31 nuclear magnetic resonance spectroscopy in vivo. AB - Diltiazem may provide a protective effect to ischemic and reperfused myocardium through preservation of high-energy phosphate metabolism. To test this hypothesis, rabbits had a 1.3 cm solenoidal coil placed over the myocardium to be rendered ischemic. Data were acquired with a 22 cm bore nuclear magnetic resonance spectrometer at 2.0 T. Animals were treated with diltiazem (200 micrograms/kg intravenous bolus of drug followed by a 15 micrograms/kg/min continuous intravenous infusion, n = 10) or by an equal volume of saline (n = 6). The left circumflex artery was occluded and reperfused using a reversible snare while electrocardiogram-gated spectra were accumulated. Levels of phosphocreatine were decreased during occlusion in both groups; however, this decrease was attenuated in the diltiazem treated animals compared to control (in relative percent area: 7.8 +/- 1.0 to 2.5 +/- 0.5, p less than 0.01). Levels of phosphocreatine promptly returned to baseline following reperfusion and there was no difference between the two groups. The inorganic phosphate metabolites of high energy phosphate consumption increased with occlusion, though more so in the control group compared with the diltiazem-treated rabbits (in relative percent area: 72.5 +/- 0.9 to 55.4 +/- 1.3, p less than 0.01). With reperfusion, levels of inorganic phosphates returned toward baseline in both groups; however, the diltiazem group had a more complete recovery relative to control (in relative percent area: 38.8 +/- 2.1 to 47.6 +/- 2.7, p less than 0.05). Levels of adenosine triphosphate decreased in both groups relative to baseline; however, the amount of decrease was similar in the two groups. With reperfusion there was a definite though incomplete recovery of levels of adenosine triphosphate in the diltiazem-treated group (in relative percent area: 10.7 +/- 1.0 at occlusion, 12.3 +/- 0.4 during reperfusion, p less than 0.05), but in the control group levels of adenosine triphosphate remained depressed (in relative percent area: 9.8 +/- 0.6 at occlusion, 9.8 +/- 0.8 during reperfusion, p = NS). During ischemia there was a trend toward attenuation of intracellular acidosis in the diltiazem group; however, this trend did not reach statistical significance. These data indicate that diltiazem provides a protective effect on myocardial high-energy phosphate metabolism during regional ischemia and reperfusion in the intact animal. PMID- 2589163 TI - Influence of positive inotropic agents on intracellular calcium transients. Part I. Normal rat heart. AB - This study, which was designed to evaluate the effects of positive inotropic agents on intracellular calcium transients ([Ca2+]i), is the first to analyze calcium transients in the whole heart. The positive inotropic agents that augment intracellular cyclic adenosine monophosphate (cAMP) (dibutyryl cAMP, amrinone, and isoproterenol) caused an increase in developed pressure and [Ca2+]i transients and a decrease in diastolic [Ca2+]i. On the other hand, the glycoside digoxin and the alpha-adrenoceptor agents, phenylephrine and dobutamine, also caused an increase in [Ca2+]i transients and developed pressure. However, unlike the agents that increase [cAMP]i, they induced an elevation in diastolic [Ca2+]i. With all the positive inotropic agents, developed pressure increased commensurately with the percentage changes in amplitude of the [Ca2+]i transients. PMID- 2589164 TI - Influence of positive inotropic agents on intracellular calcium transients. Part II. Cardiomyopathic hamster hearts. AB - To study the mechanism of dobutamine on end-stage heart failure, we assessed hemodynamic responses, high-energy phosphates (31P-NMR), and free intracellular calcium ([Ca2+]i) transients (surface fluorometry) during perfusion with 10(-6) mol/L dobutamine in Syrian cardiomyopathic hamsters with severe heart failure. These results were compared to perfusion of the heart with 10(-6) mol/L norepinephrine and 10(-6) mol/L isoproterenol. With the positive inotropic agents the rate-pressure product increased immediately (p less than 0.01 with dobutamine, norepinephrine; p less than 0.003 with isoproterenol); after 10 to 15 minutes of perfusion the rate-pressure product remained relatively stable with norepinephrine and isoproterenol but decreased with dobutamine (p = NS vs control values). [Ca2+]i-transients increased significantly in all groups. The end diastolic [Ca2+]i decreased continuously with norepinephrine and isoproterenol (p less than 0.008; p less than 0.005) but increased during dobutamine by 19%. Alterations in coronary flow, pHi, high-energy phosphates, and the phosphorylation potential were not significantly different among the three catecholamines. In conclusion, in contrast to norepinephrine and isoproterenol, dobutamine depressed myocardial performance and increased end-diastolic [Ca2+]i in late heart failure. PMID- 2589165 TI - Preload, adrenergic activity, and aortic compliance in normal and hypertensive patients. AB - Aortic compliance is a major determinant of systolic blood pressure and of impedance to left ventricular ejection. However, little is known about its regulating factors. To assess the effects of preload and adrenergic activity on aortic compliance, we studied 10 normal subjects and nine untreated hypertensive patients at rest and during lower body negative pressure. Aortic compliance was measured invasively from the diastolic decay of the aortic pressure tracing and systemic vascular resistance. Preload was decreased stepwise by lower body negative pressure (-5 to -40 mm Hg) while adrenergic activity was assessed by the change in plasma norepinephrine at a maximum level of negative pressure suction. At rest, aortic compliance was lower in hypertensive subjects compared with its value in normal individuals (0.048 +/- 0.012 [SD] versus 0.071 +/- 0.009 units, p less than 0.001) but correlated inversely with systolic blood pressure in both groups (r = -0.64 in normotensive individuals, r = -0.83 in hypertensive subjects, r = -0.88 for the whole group, p less than 0.001 for all). Whereas resting pulmonary wedge pressure was higher in hypertensive subjects compared with normal individuals (16 +/- 4 [SD] versus 11 +/- 3 mm Hg, p less than 0.05), resting plasma norepinephrine levels were not different between the two groups (261 +/- 139 versus 251 +/- 103 pg/ml). Neither of these two resting indices correlated with baseline aortic compliance in both normotensive individuals and hypertensive patients. During lower body negative pressure (LBNP), cardiac filling pressure (right atrial pressure and pulmonary wedge pressure) as well as cardiac output decreased in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589166 TI - Responsiveness of the maximum time-varying elastance to alterations in left ventricular contractile state in man. AB - This investigation was designed to establish the relative responsiveness of maximum time-varying elastance (Emax) slope values to alterations in left ventricular contractile state in comparison with isovolumic and ejection phase indices in man. Accordingly, nine patients had a bipolar right atrial pacing catheter and micromanometer left ventricular catheter placed and red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamic measurements and radionuclide angiograms were acquired simultaneously over a range of loading conditions produced by methoxamine or nitroprusside infusions during both the basal and enhanced contractile states. Enhanced left ventricular contractility was produced by a steady-state dobutamine infusion of 2 to 10 mu/kg/min. The mean (+)dP/dtmax increased from 1510 +/- 460 mm Hg/sec during the basal state to 2537 +/- 546 mm Hg/sec (p less than 0.001) during the dobutamine infusion. The mean Emax slope value also increased from 4.34 +/- 1.40 mm Hg/ml during the basal state to 6.41 +/- 1.90 mm Hg/ml (p less than 0.001) during the dobutamine infusion. The average percent change in the Emax slope value (51 +/- 26%) was less than those for the isovolumic indices (57% to 112%), while it was more than those for the ejection phase indices (11% to 53%). When the variability in the percent changes for each of these contractile indices was incorporated into the analysis, the Emax slope values demonstrated a greater responsiveness to changes in left ventricular contractility than did the isovolumic and ejection phase indices. In conclusion, the Emax slope value calculated by this method is a contractile index, which is less affected by measurement variability and the influences of loading conditions than are the isovolumic and ejection phase indices, and therefore may improve our ability to both detect and quantitate changes in left ventricular contractility in man. PMID- 2589167 TI - Combined laser-thermal and atherectomy treatment of peripheral arterial occlusion: documentation by angioscopy and angiography. PMID- 2589168 TI - Septal ischemia and abnormal septal Q wave response to exercise: a link implicated from percutaneous transluminal coronary angioplasty. PMID- 2589169 TI - Role of transesophageal echocardiography in the diagnosis of papillary muscle rupture secondary to myocardial infarction. PMID- 2589170 TI - Threatening arrhythmias in acute myocardial infarction are prevented by intravenous magnesium sulfate. PMID- 2589171 TI - Repeated intravascular treatment with amiodarone in a fetus with refractory supraventricular tachycardia and hydrops fetalis. PMID- 2589172 TI - Unusual origin of the S-shaped (posterior) sinus node artery. PMID- 2589173 TI - Coronary sinus dilatation in acute pulmonary embolism. PMID- 2589174 TI - Apical hypertrophic cardiomyopathy. PMID- 2589175 TI - Parasystole versus escape rhythm. PMID- 2589176 TI - Pericarditis in AMI. PMID- 2589177 TI - Progression of coronary disease. PMID- 2589178 TI - CAD progression criteria. PMID- 2589179 TI - Left ventricular diastolic filling in coronary artery disease. PMID- 2589180 TI - Angiotensin converting enzyme inhibitors. PMID- 2589181 TI - Automatic implantable cardioverter-defibrillator. PMID- 2589182 TI - Bradycardia-dependent Kent bundle block. PMID- 2589183 TI - Percutaneous aortic balloon valvuloplasty. PMID- 2589184 TI - Hibernating myocardium. PMID- 2589185 TI - Early and late results of coronary angioplasty without antecedent thrombolytic therapy for acute myocardial infarction. AB - Direct coronary angioplasty without antecedent thrombolytic therapy was performed in 500 consecutive patients with acute myocardial infarction. Anterior and inferior infarctions were noted in 217 and 283 patients, respectively. Two hundred fifteen patients (43%) had 1-vessel disease, 85 patients (17%) were greater than 70 years of age and 39 (8%) presented in cardiogenic shock. Successful angioplasty of the infarct vessel was achieved in 94% of patients. The overall in-hospital mortality was 7.2%. Cardiogenic shock, 3-vessel disease and failed angioplasty were the 3 strongest multivariate correlates of early mortality. Reocclusion of the infarct-vessel was noted in 47 (15%) of the 307 patients with angiographic follow-up before hospital discharge. Significant bleeding complications occurred in only 3% of patients; stroke or myocardial rupture was not seen. The global ejection fraction increased from 53% on the preangioplasty ventriculograms to 59% at 1 week (p less than 0.001). Significant regional wall motion improvement in the infarct segments was noted in 53% of patients. Global ejection fraction improved most dramatically in patients presenting with baseline ejection fractions less than or equal to 45% (increasing from 36 to 50%). The 1- and 5-year survival rates after hospital discharge were 95 and 84%, respectively. The 1-year reinfarction rate was 3%. Thus, direct coronary angioplasty was highly effective in reestablishing infarct-vessel patency and salvaging ischemic myocardium, resulting in low in-hospital and long term mortality. PMID- 2589186 TI - Cardiac event rate after non-Q-wave acute myocardial infarction and the significance of its anterior location. AB - To correlate cardiac event rate with infarct location on the electrocardiogram in patients recovering from a non-Q-wave acute myocardial infarction (AMI), 135 consecutive patients with enzymatically proven non-Q-wave AMI were followed prospectively for a median of 9.9 months. Of these, 65 patients were classified as having had an anterior non-Q-wave AMI, defined as new ST- or T-wave changes, or both, in leads V1 through V4 (group 1). The remaining 70 patients were classified as having had inferior or lateral non-Q-wave AMI, or both, defined as ST- or T-wave changes in 2 consecutive leads (II, II aVF; II and aVL or V5 and V6) (group 2). At baseline group I was older and had a higher incidence of previous AMI than group 2. After adjusting for baseline variables, the patients in group I had a 29% reinfarction and 32% mortality rate, which was significantly higher (p less than 0.002 for both) when compared to group 2, which had a reinfarction and mortality rate of 8 and 9%, respectively. Patients with anterior non-Q-wave AMI are at very high risk for developing a major cardiac event very soon after the index AMI. This high risk is probably related to a larger area of residual ischemic but viable myocardium in the infarct-related artery when compared to inferolateral non-Q-wave AMI. PMID- 2589187 TI - Prognostic utility of predischarge dipyridamole-thallium imaging compared to predischarge submaximal exercise electrocardiography and maximal exercise thallium imaging after uncomplicated acute myocardial infarction. AB - The prognostic value of predischarge dipyridamole-thallium scanning after uncomplicated myocardial infarction was determined by comparison with submaximal exercise electrocardiography and 6-week maximal exercise thallium imaging and by correlation with clinical events. Two endpoints were defined: cardiac events and severe ischemic potential. Of the 40 patients studied, 8 had cardiac events within 6 months (1 died, 3 had myocardial infarction and 4 had unstable angina requiring hospitalization). The finding of any redistribution on dipyridamole thallium scanning was common (77%) in these patients and had poor specificity (29%). Redistribution outside of the infarct zone, however, had equivalent sensitivity (63%) and better specificity (75%) for events (p less than 0.05). Both predischarge dipyridamole-thallium and submaximal exercise electrocardiography identified 5 of the 8 events (p = 0.04 and 0.07, respectively). The negative predictive accuracy for events for both dipyridamole thallium and submaximal exercise electrocardiography was 88%. In addition to the 8 patients with events, 16 other patients had severe ischemic potential (6 had coronary bypass surgery, 1 had inoperable 3-vessel disease and 9 had markedly abnormal 6-week maximal exercise tests). Predischarge dipyridamole-thallium and submaximal exercise testing also identified 8 and 7 of these 16 patients with severe ischemic potential, respectively. Six of the 8 cardiac events occurred before 6-week follow-up. A maximal exercise thallium test at 6 weeks identified 1 of the 2 additional events within 6 months correctly. Thallium redistribution after dipyridamole in coronary territories outside the infarct zone is a sensitive and specific predictor of subsequent cardiac events and identifies patients with severe ischemic potential.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589188 TI - Initial angiographic results in ablation of atherosclerotic plaque by percutaneous coronary excimer laser angioplasty without subsequent balloon dilatation. AB - Percutaneous transluminal coronary excimer laser angioplasty was performed in 15 patients using a 1.3-mm diameter laser catheter. The catheter consists of 20 concentric quartz fibers of 100 microns diameter each located around a central lumen suitable for a 0.014-inch flexible guidewire. The catheter was coupled to an excimer laser delivering energy at a wavelength of 308 nm and at a pulsewidth of 60 ns. Quantitative analysis of the angiograms documented a decrease from 77 +/- 15% diameter stenosis before intervention to 40 +/- 22% after the first irradiation cycle and to 21 +/- 17% after termination of laser ablation. The minimal lumen diameter increased from 0.4 +/- 0.2 to 1.3 +/- 0.4 and to 1.6 +/- 0.4 mm, respectively. Vessel reocclusion was seen in 2 patients at 24-hour control angiography. No procedure-related major complications such as vessel perforation occurred. In 8 patients, however, intraluminal lucencies were seen, which were persistently visualized 24 hours after intervention in 6 patients. Despite pretreatment with intracoronary nitroglycerin, coronary spasm occurred in 8 patients and was reversible after additional sublingual vasodilator therapy. The results of this pilot study suggest that percutaneous coronary excimer laser angioplasty is feasible and effective for ablation of coronary lesions in selected patients and can be performed without subsequent conventional balloon angioplasty. The clinical impact of this new interventional technique, however, remains to be assessed. PMID- 2589189 TI - Percutaneous cardiopulmonary bypass support in high-risk patients undergoing percutaneous transluminal coronary angioplasty. AB - Fifty-one consecutive patients in whom percutaneous cardiopulmonary bypass support was instituted to enhance the safety of high-risk elective coronary angioplasty were studied. All patients had a low ejection fraction, a large amount of viable myocardium perfused by the target artery(s) or both. Thirty-five men and 16 women, mean age 63 years, with Canadian Cardiovascular Society class III angina (23 patients) or class IV (28 patients) were studied. There was a history of myocardial infarction in 45 (88%), bypass surgery in 14 (27%) and congestive heart failure in 17 (33%). Forty-six (90%) had impaired left ventricular function. Twenty (39%) had an ejection fraction of less than or equal to 25%. Left main stenosis was present in 9 (18%), 3-vessel disease in 48 (94%) and 2-vessel disease in 2 (4%). Twenty (39%) were considered at a prohibitive risk for bypass surgery (14 were turned down for surgery). Bypass was instituted percutaneously with flows ranging from 2 to 5 liters/min (mean 3.6). Angioplasty was successful in 115 of the 117 lesions attempted with the culprit vessel dilated in all. Dilatation of the only remaining vessel was performed in 14 (27%). Inflation times up to 10 minutes were well tolerated. Bypass was discontinued after a mean bypass time of 37 minutes. Hemostasis was achieved by external clamp compression in 50. There were 3 hospital deaths unrelated to bypass. Patient follow-up at 2 to 8 months (mean 4.9) disclosed 1 late death, 31 (66%) asymptomatic patients, 12 (26%) patients in class I and 4 patients (9%) in class II. Thus, this study demonstrates the safety and efficacy of percutaneous bypass support in selected patients undergoing high-risk coronary angioplasty. PMID- 2589190 TI - Predictors of success in percutaneous transluminal coronary angioplasty of chronic total occlusions. AB - Earlier studies have indicated that percutaneous transluminal coronary angioplasty (PTCA) of chronic total occlusions has a low success rate. To determine success rate and assess clinical and angiographic variables associated with success and complications, 57 total occlusions in 56 patients undergoing PTCA were analyzed. The clinical duration of occlusion was 51 +/- 86 days. Success (less than 50% residual stenosis) was achieved at 40 of 57 (70%) dilatation sites. Of these 57 total occlusions, 5 were attempted within 24 hours of acute myocardial infarction, 35 between 1 day and 8 weeks of clinical occlusion, 13 greater than 8 weeks and 4 were of unknown duration. Success rates were 4 of 5, 25 of 35, 9 of 13 and 2 of 4, respectively, in each group (difference not significant, comparison of all time groups). Of the 9 narrowings with a successful PTCA for an occlusion greater than 8 weeks, the mean duration of occlusion was 93 +/- 41 days (range 60 to 180). None of the attempted dilatations of occlusions with a clinical duration of greater than 180 days (n = 3) was successful. None of the clinical or angiographic variables (including tortuosity, length of occlusion gap, distance of the occlusion from the vessel origin, thrombus, lesion calcium, collaterals, prior myocardial infarction, vessel dilated or diffuse disease) impacted on success rate (difference not significant for all). No patient died, had a Q-wave infarction, required emergency coronary artery bypass grafting or underwent repeat PTCA within 7 days of the procedure. Non-Q-wave infarction occurred in 2 of 56 patients (4%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589191 TI - Early hospital discharge after percutaneous transluminal coronary angioplasty. AB - To determine the safety and efficacy of early hospital discharge after percutaneous transluminal coronary angioplasty (PTCA), 100 patients were studied prospectively. A telemetry observation unit was established to monitor patients having uncomplicated procedures. A total of 170 lesions were dilated, with a procedural success rate of 96% and a clinical success rate of 91%. There were no deaths or patients who required emergency bypass surgery. Four patients developed abrupt vessel closure in the catheterization laboratory. No major complications developed in the telemetry observation unit or after discharge. Patients with high-risk lesion morphology, based on the American College of Cardiology/American Heart Association Task Force guidelines, tended to have a lower success rate and more procedural complications. Coronary dissections were angiographically detected in 33 patients and stratified into 6 types. To reduce possible adverse sequelae, all patients with complex dissections were triaged in the catheterization laboratory to an in-patient monitored unit for additional management. Accordingly, 20 patients were admitted to an in-patient unit for extended observation. Excluding 4 patients with myocardial infarction, 75% (12 of 16) were discharged the next day. Initial experience with early discharge suggests that under proper conditions the procedure is safe and effective. Patients with complex coronary dissections who are at high risk for abrupt vessel closure can be promptly identified after dilatation and triaged to an appropriate monitoring area. Early discharge after PTCA offers more efficient use of hospital facilities and the opportunity to reduce hospital costs. PMID- 2589192 TI - Predictive value of quantitative dipyridamole-thallium scintigraphy in assessing cardiovascular risk after vascular surgery in diabetes mellitus. AB - Cardiac complications represent a major risk to patients undergoing vascular surgery. Diabetic patients may be particularly prone to such complications due to the high incidence of concomitant coronary artery disease, the severity of which may be clinically unrecognized. Attempts to stratify groups by clinical criteria have been useful but lack the predictive value of currently used noninvasive techniques such as dipyridamole-thallium scintigraphy. One hundred one diabetic patients were evaluated with dipyridamole-thallium scintigraphy before undergoing vascular surgery. The incidence of thallium abnormalities was high (80%) and did not correlate with clinical markers of coronary disease. Even in a subgroup of patients with no overt clinical evidence of underlying heart disease, thallium abnormalities were present in 59%. Cardiovascular complications, however, occurred in only 11% of all patients. Statistically significant prediction of risk was not achieved with simple assessment of thallium results as normal or abnormal. Quantification of total number of reversible defects, as well as assessment of ischemia in the distribution of the left anterior descending coronary artery was required for optimum predictive accuracy. The prevalence of dipyridamole-thallium abnormalities in a diabetic population is much higher than that reported in nondiabetic patients and cannot be predicted by usual clinical indicators of heart disease. In addition, cardiovascular risk of vascular surgery can be optimally assessed by quantitative analysis of dipyridamole-thallium scintigraphy and identification of high- and low-risk subgroups. PMID- 2589193 TI - Clinical correlates and prognostic significance of type A behavior and silent myocardial ischemia on the treadmill. AB - Type A patients with coronary artery disease (CAD) tend to ignore or underreport symptoms, especially during challenging tasks such as the treadmill exercise test. To determine whether type A CAD patients might be more likely than type B patients to have silent ischemia during exercise and consequently a worse prognosis, 403 patients with stable CAD who had significant coronary disease on angiography, a positive Bruce protocol treadmill test and a structured interview to assess type A behavior were studied. Median follow-up time was 6 years. Type A patients were more likely to experience silent ischemia during exercise than were type B patients (35 vs 25%, p = 0.05). Patients with silent ischemia during exercise had a history of fewer anginal episodes/week, and type A patients with silent ischemia were less likely to have had a history of typical angina. However, using the Cox model, there were no significant differences in survival between type A patients and B patients with silent ischemia (4-year survival 86 vs 79%, p = 0.44) and no significant differences in survival between type A patients with silent ischemia and type A patients with symptomatic ischemia (6 year survival 86 vs 80%, p = 0.59). Similar results were obtained for infarction free survival. Type A patients are more likely than type B patients to have silent ischemia during exercise, but long-term survival is not affected. PMID- 2589194 TI - Prognosis in patients with a strongly positive exercise electrocardiogram. AB - In patients with a strongly positive exercise electro-cardiogram, the workload achieved during the test allows the identification of subsets with good or poor survival rates. To determine whether the same criteria also predict acute ischemic heart events such as unstable angina and myocardial infarction, fatal and nonfatal acute manifestations were documented in 241 patients medically treated during an 8-year follow-up. All patients had a Bruce protocol treadmill exercise test with ST-segment depression greater than or equal to 2 mm and coronary angiographic studies. There were 52 deaths; of these 44 were due to coronary artery disease. There were 41 episodes of unstable angina and 21 myocardial infarcts documented as first morbid events. As expected, survival improved with increased workload achieved; patients terminating their exercise at stage I (5.1 METs) had an 8-year survival rate of 45 +/- 9% while those reaching stage IV or more (10 METs) had a survival rate of 93 +/- 6%. In a multivariate analysis, the duration of exercise and the number of narrowed coronary arteries and of left ventricular segment abnormalities correlated significantly with survival. In contrast, nonfatal acute events occurred in about 20 to 35% of patients whatever the stage of the exercise test. Furthermore, neither variables during the exercise test nor angiographic findings predicted nonfatal events. Thus, although the workload achieved did identify patients with different mortality rates, it failed to predict subsets of patients with different morbid event rates. PMID- 2589195 TI - Argon laser ablation of malignant ventricular tachycardia associated with coronary artery disease. AB - The long-term clinical efficacy and safety of intraoperative mapping-guided argon laser ablation alone or in conjunction with standard surgical methods were assessed in 20 consecutive patients with refractory sustained ventricular tachycardia (VT) or ventricular fibrillation. A 15-W argon ion gas laser was used and pulsed laser energy was delivered through a fiberoptic catheter delivery system. Pre- and intraoperative mapping was used to localize the arrhythmogenic tissue. Postoperative clinical, ambulatory electrocardiographic and electrophysiologic evaluations were performed before discharge and at 1 year of follow-up. Thirty-eight VT morphologies were mapped and ablated with laser energy alone (82%), combined laser ablation and mechanical resection (13%) or mechanical resection alone (5%). Concomitant coronary artery bypass surgery was performed in 15 patients and in 1 patient it was performed with mitral value replacement. Postoperative 30-day mortality was 5%. One patient (5%) required postoperative antiarrhythmic drug therapy, and all survivors had suppression of inducible sustained VT at discharge. Mean left ventricular ejection fraction increased from 34 +/- 12% preoperatively to 41 +/- 13% postoperatively (p = 0.001). Efficacy rates for ablation of VT sites associated with anterior myocardial infarction and inferior or posterior myocardial infarction were comparable (100 vs 96%, respectively, p greater than 0.2). At 1-year follow-up no sudden deaths had occurred and total survival rate was 90%. Intraoperative pulsed argon laser ablation alone or in conjunction with standard surgical techniques improves the efficacy of surgical ablation procedures for VT or ventricular fibrillation and reduces the need for additional postoperative antiarrhythmic drug or device therapy. PMID- 2589197 TI - Comparison of adenosine and verapamil for termination of paroxysmal junctional tachycardia. AB - The effects of intravenous adenosine and intravenous verapamil on paroxysmal junctional tachycardia were compared in 20 patients undergoing invasive cardiac electrophysiologic study. In 13 patients the diagnosis was of a reentrant tachycardia using an extranodal accessory connection (atrioventricular [AV] reentrant tachycardia); 5 of these patients had overt preexcitation in sinus rhythm, 4 had concealed accessory connections and 4 had latent or intermittent preexcitation. In 7 patients the diagnosis was of an AV nodal reentrant tachycardia. Administration of adenosine resulted in termination of tachycardia in all 20 patients at a mean dose of 0.125 mg/kg (range 0.05 to 0.20). Although termination of tachycardia was frequently accompanied by atrial and ventricular premature complexes, no significant arrhythmias were observed after conversion. Administration of verapamil (0.145 mg/kg) resulted in termination of tachycardia in 19 of 20 patients but was followed by symptomatic arrhythmias in 2: preexcited atrial flutter in 1 patient and preexcited atrial tachycardia in another. Latent or intermittent preexcitation was unmasked in 4 of 4 patients immediately after termination of tachycardia by adenosine. Termination of tachycardia by verapamil revealed preexcitation in only 1 of these 4 patients. Analysis of results in terms of successful termination of tachycardia, absence of significant arrhythmias after conversion and unmasking of latent or intermittent preexcitation reveals that adenosine therapy was satisfactory in all 20 patients, whereas verapamil was satisfactory in only 14 of the 20 patients (p less than 0.05). All 6 of the patients with unsatisfactory responses to verapamil had AV reentrant tachycardia. These results suggest that adenosine has particular advantages over verapamil as acute treatment for patients presenting with an AV reentrant tachycardia. PMID- 2589196 TI - Efficacy of intravenous propranolol for suppression of inducibility of ventricular tachyarrhythmias with different electrophysiologic characteristics in coronary artery disease. AB - The efficacy of intravenous propranolol for suppression of inducibility of sustained ventricular tachyarrhythmias (VT) was studied in 24 patients who had failed greater than or equal to 1 membrane-active antiarrhythmic drug (mean 2.2 +/- 1.2 drugs/patient). The response to propranolol was compared in 13 patients who had only stable monomorphic VTs inducible at baseline and another 11 patients who had greater than or equal to 1 episode of electrically unstable VTs (polymorphic VT, ventricular flutter or ventricular fibrillation) at baseline. Seven patients (29%) became noninducible (responders) and 17 patients (71%) remained inducible to sustained VT (nonresponders) after propranolol. The basal heart rate was faster in responders than in nonresponders (101 +/- 14 vs 86 +/- 11 beats/min, p less than 0.01). The magnitude of heart rate reduction was also greater after propranolol in responders (from 101 +/- 14 to 80 +/- 9 beats/min, p less than 0.001) than in nonresponders (from 86 +/- 11 to 74 +/- 9 beats/min, p less than 0.01) (p less than 0.05 between the groups), despite equal plasma propranolol concentrations (84 +/- 50 vs 88 +/- 43 ng/ml, difference not significant). Seven of 11 patients (64%) who had greater than or equal to 1 episode of unstable VTs inducible at baseline responded to intravenous propranolol, whereas none of the patients with only stable monomorphic VTs became noninducible after beta blockade (p less than 0.001). Responders had shorter cycle length of inducible VTs than nonresponders (225 +/- 38 vs 302 +/- 66 ms, p less than 0.001). Thus, intravenous propranolol appears to be efficacious in suppressing fast, electrically unstable VTs, compared to monomorphic VTs with slower rates. PMID- 2589199 TI - Operative therapy of atrioventricular node reentry and results of an anatomically guided procedure. AB - Operative therapy for atrioventricular (AV) node reentrant tachycardia consisting of dissection guided by anatomic landmarks is described. Of the 21 patients studied, 17 had the common type ("slow-fast") and 4 had the uncommon type ("fast slow") of AV node reentry. Under normothermic cardio-pulmonary bypass, perinodal dissection was performed guided by anatomic landmarks: the atrial membranous septum, posterior superior process of the left ventricle, tendon of Todaro and os of the coronary sinus. There were no deaths or major complications. Seven to 10 days postoperatively, all patients had normal AV conduction except for one who continued to have AV node Wenckebach-type block. Postoperatively, the shortest cycle length capable of 1:1 conduction over the AV node changed from 323 +/- 66 to 421 +/- 90 ms (p less than 0.0001) anterogradely and from 330 +/- 86 to 449 +/ 164 ms (p = 0.004) retrogradely. Anterograde effective refractory period of the AV node prolonged from 264 +/- 49 to 358 +/- 107 ms (p = 0.012). Discontinuous AV conduction curves were no longer seen in 14 of 17 patients and 5 patients lost retrograde conduction. During follow-up (14.8 +/- 8.2 months), 19 patients have been free of arrhythmia without medication. Two patients required a second operation for recurrent tachycardia with success. No patient required a permanent pacemaker. These data show that operative therapy of AV node reentrant tachycardia can be guided by anatomic landmarks. Successful cure of tachycardia with perinodal dissection while preserving AV node conduction supports the view that the reentrant circuit is, at least in part, perinodal. PMID- 2589198 TI - Usefulness of serial pulmonary function testing as an indicator of amiodarone toxicity. AB - A prospective study was conducted of 189 patients treated with amiodarone, maintained at doses of 400 to 800 mg/day and followed for up to 6 years. Only patients who had life-threatening ventricular arrhythmias unresponsive to conventional therapy were enrolled, and they underwent baseline pretreatment pulmonary function tests, with follow-up testing every 6 months. Morbidity and mortality statistics were confirmed by chart review and patient telephone interview. Of the 189 enrolled patients, 101 are alive, 84 are dead and 4 are lost to follow-up. Amiodarone-induced toxicity to the neurologic system, lungs, thyroid or liver was the primary or complicating cause of death in 12 of the 84 patients who died. The overall prevalence of all these forms of toxicity was 15%. Sixty-nine percent of the patients with amiodarone toxicity had pulmonary toxicity alone or combined with other forms of toxicity. Pulmonary function test abnormalities were noted at baseline in 75% of patients who had amiodarone induced toxicity. The proportion of abnormal baseline pulmonary function tests was not significantly different among all toxic patients, pulmonary toxic patients and nontoxic patients. An evaluation of the decrease in pulmonary function over time could not distinguish patients who developed toxicity from those who did not. The observed incidence of pulmonary toxicity is consistent with published values; however, contrary to the findings of others, no statistically significant differences in pulmonary function at baseline or in changes over time were found between toxic and nontoxic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589200 TI - Ability of left ventricular stress-shortening relations, end-systolic stress/volume ratio and indirect indexes to detect severe contractile failure in ischemic or idiopathic dilated cardiomyopathy. AB - The ability of several proposed indirect and direct indexes of left ventricular LV) systolic performance and contractility to detect clinically important LV dysfunction was evaluated in 42 patients with refractory dilated cardiomyopathy studied with right-sided heart catheterization and M-mode echocardiography. Hemodynamic evaluation demonstrated elevated filling pressure (mean pulmonary artery wedge pressure 24 +/- 6 mm Hg) and depressed function (cardiac index 1.68 +/- 0.43 liters/min/m2). Echocardiographic LV end-diastolic dimension (7.3 +/- 1.0 cm), mass (182 +/- 60 gm/m2) and end-systolic stress (163 +/- 44 x 10(3) dynes/cm2) were increased whereas fractional shortening was depressed in all (mean 12 +/- 4%). During follow-up 88% of patients died at a median interval of 16 months after study. Indirect measurements of LV function (mitral E point septal separation and the ratio of preejection period to LV ejection time) were abnormal in 100 and 88% of patients, respectively. Contractility was classified as depressed in 36 (86%) patients by the end-systolic stress volume index ratio and in 31 (74%) by the relation between fractional shortening and end-systolic stress. In contrast, the relation between end-systolic stress and velocity of circumferential shortening identified only 7 (17%) patients as having subnormal contractility and classified 9 (21%) as having supernormal contractility. Rate correction of velocity of circumferential shortening only modestly improved the ability of the relation to identify depressed contractility (abnormal in 16 patients or 38 percent). PMID- 2589201 TI - Long-term predictors of sudden and low output death in chronic congestive heart failure secondary to coronary artery disease. AB - Clinical, hemodynamic and neurohumoral variables in 238 patients with chronic congestive heart failure (CHF) secondary to coronary artery disease were analyzed to determine potential predictors of mortality in a large population and to allow analysis according to mode of death (sudden or low output death). All variables were assessed before initiation of treatment with vasodilators (converting enzyme inhibitors, direct acting vasodilators) or with the nonglycoside, noncatecholamine class of inotropic agents. Survival outcome was determined as alive, sudden death or low output death. When all variables except ejection fraction were analyzed by Cox multiple regression analysis, the most important independent predictor of all deaths was the baseline plasma renin activity (p less than 0.001). When subdivided by cause of cardiovascular death, baseline plasma renin activity was retained as the most important determinant of low output death (p less than 0.001), whereas baseline left ventricular stroke work index (p less than 0.001), pulmonary capillary wedge pressure (p less than 0.002) and absence of sinus rhythm (p less than 0.006) were the most powerful independent predictors of sudden death. Plasma norepinephrine was markedly elevated in the group dying of low output, but only modestly elevated in the group of survivors and the group dying suddenly. However, baseline norepinephrine was not found to be an important independent predictor of mortality in any of the subgroups. Plasma renin activity, but not plasma norepinephrine, is a powerful independent prognostic determinant of mortality in this group of patients with CHF. PMID- 2589202 TI - Quantitation and significance of systolic mitral leaflet displacement in mitral valve prolapse. AB - Superior systolic displacement of the mitral leaflets is the echocardiographic finding generally used to diagnose mitral valve prolapse, but its clinical significance is not clearly established. This study was designed to determine if the presence of leaflet thickening, displacement in the multiple imaging planes or the quantitative degree of displacement could be used to identify clinically important valvular abnormality. To this end, these findings were prospectively assessed and correlated with the presence of mitral regurgitation and ventricular arrhythmia in 49 patients with displacement and in 49 age-matched control subjects with no identifiable displacement. Both ventricular arrhythmia and mitral regurgitation were found to occur with significantly greater frequency in patients with leaflet displacement than in control subjects. However, among the patients with leaflet displacement, both these complications occurred with greater frequency in subgroups characterized by the presence of leaflet thickening, quantitatively greater displacement and displacement evident in 2 orthogonal imaging planes. Logistic regression analysis demonstrated that the best echocardiographic predictor of either ventricular arrhythmia or mitral regurgitation was the quantitative degree of leaflet displacement. These results indicate that most patients with echocardiographic evidence of leaflet displacement had very low incidences of ventricular arrhythmia and mitral regurgitation. Subgroups, however, could be identified echocardiographically in which both complications occurred with significantly greater frequency. PMID- 2589203 TI - Intermediate-term follow-up results of balloon aortic valvuloplasty in infants and children with special reference to causes of restenosis. AB - Sixteen infants and children with valvular aortic stenosis underwent percutaneous balloon aortic valvuloplasty over a 36-month period ending August 1988. The mean systolic pressure gradient across the aortic valve decreased from 72 +/- 21 (mean +/- standard deviation) to 28 +/- 13 mm Hg (p less than 0.001) immediately after valvuloplasty; the degree of aortic insufficiency did not significantly increase. Follow-up catheterization (in 10 patients) and Doppler data (in all 16 patients) were available 3 to 32 months (mean 12 months) after valvuloplasty and revealed a residual aortic valvular gradient of 37 +/- 23 mm Hg, which continues to be significantly lower (p less than 0.001) than that before valvuloplasty. There was no increase in aortic insufficiency. On the basis of follow-up data, the 16 children were divided into 2 groups: group I with good results (gradients less than or equal to 49 mm Hg), 12 patients; and group II with poor results (gradients greater than or equal to 50 mm Hg), 4 patients. All 4 patients in group II required repeat balloon valvuloplasty or surgical valvotomy; none from group I required these procedures. Seventeen general, anatomic, physiologic and technical variables were examined by a multivariate logistic regression analysis to identify factors associated with restenosis; these risk factors were: age less than or equal to 3 years; and immediate aortic valvular gradient after valvuloplasty greater than or equal to 30 mm Hg. The immediate and intermediate term follow-up results of balloon aortic valvuloplasty are encouraging. Recognition of the risk factors may help identify potential candidates for recurrence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589204 TI - Effect of exercise and cavity size on right ventricular function in morbid obesity. AB - To assess the effect of exercise and to determine the influence of the right ventricular (RV) internal dimension on RV systolic function in morbid obesity, M mode and 2-dimensional echocardiography and radionuclide ventriculography were performed on 22 patients whose body weight was at least twice the ideal body weight and who had no clinical or laboratory evidence of underlying organic heart disease or pulmonary disease. RV ejection fraction was measured at rest and during peak supine bicycle exercise. RV exercise response was defined as the change in RV ejection fraction during peak exercise. There was a significant negative correlation between percent over ideal body weight and RV exercise response (r = 0.86, p less than 0.00005) and between RV internal dimension and RV exercise response (r = 0.60, p less than 0.005). There were significant positive correlations between resting RV and left ventricular (LV) ejection fraction (r = 0.56, p less than 0.01) and between RV and LV exercise response (r = 0.70, p less than 0.0005). The subgroup with a high-normal or enlarged RV internal dimension (greater than or equal to 2.0 cm, n = 10) experienced no significant change in RV ejection fraction with exercise, whereas the subgroup whose RV internal dimension was less than 2.0 (n = 12) experienced a significant increase in RV ejection fraction from 44 +/- 10% at rest to 58 +/- 11% at peak exercise (p less than 0.03). The results suggest that in morbidly obese individuals without underlying cardiopulmonary disease RV dilatation may predispose to RV systolic dysfunction and assessment of RV systolic function should optimally include evaluation of RV exercise response. PMID- 2589206 TI - Frequency of symptoms suggestive of dynamic coronary artery disease in patients referred for coronary angiography. PMID- 2589205 TI - Prospective Doppler echocardiographic evaluation of pulmonary artery diastolic pressure in the medical intensive care unit. AB - To test the hypothesis that the noninvasive evaluation of pulmonary regurgitation can provide accurate estimates of pulmonary artery (PA) diastolic pressures and PA wedge pressures, Doppler echocardiographic studies were performed immediately before bedside PA catheterization in 29 medical intensive care unit patients. The characteristic color flow Doppler signal of pulmonary regurgitation was detected in 19 (66%) patients. In 17 of the 29 patients (59%), the gradient between the right ventricle and PA at end-diastole could be calculated from the pulsed-wave Doppler signal of pulmonary regurgitation using the simplified Bernoulli equation. Right atrial pressure was then estimated by examination of the jugular venous pulse or by electronic transduction of the pressure signal from a previously placed central venous catheter. A noninvasive estimate of PA diastolic pressure was made by adding the clinical estimate of right atrial pressure to the end-diastolic pressure gradient across the pulmonary valve. Pulmonary artery catheterization was then performed and stripchart recordings were interpreted by a physician who was unaware of the noninvasively-estimated PA diastolic pressure. The PA diastolic pressure estimated by Doppler echocardiography correlated closely with that found at catheterization (r = 0.94, mean absolute difference 3.3 mm Hg). The noninvasive estimate of PA diastolic pressure also correlated with the PA wedge pressure (r = 0.87, mean absolute difference 3.8 mm Hg). Therefore, in 59% of medical intensive care unit patients, Doppler echocardiographic evaluation of pulmonary regurgitation allowed accurate noninvasive estimation of PA diastolic pressure. PMID- 2589207 TI - Influence of cardiac pacing mode on the long-term development of atrial fibrillation. PMID- 2589208 TI - Effects of low altitude exposure on 24-hour blood pressure and adrenergic activity. PMID- 2589209 TI - Comparison of results of percutaneous balloon mitral valvotomy using consecutive single (25 mm) and double (25 mm and 12 mm) balloon techniques. PMID- 2589210 TI - Color flow Doppler evaluation of St. Jude Medical prosthetic valves. PMID- 2589211 TI - Color flow Doppler evaluation of cardiac bioprosthetic valves. PMID- 2589212 TI - Analysis of calcium, zinc, magnesium, iron and copper content in myocardium and stenotic mitral valves. PMID- 2589213 TI - Mechanism of disappearance of S3 with maturation. PMID- 2589214 TI - In vivo relation between cineangiographic jet width and jet width imaged by color coded Doppler. PMID- 2589215 TI - Diagnostic role of intraoperative epicardial echocardiography following complications of mitral valve replacement with the Bjork-Shiley prosthetic valve. PMID- 2589216 TI - Mitral valve replacement for mitral lipoma associated with severe obesity. PMID- 2589217 TI - Osteoclast biology in the osteopetrotic (op) rat. AB - Osteopetrosis is a metabolic bone disease characterized by reduced bone resorption. From experimental studies of various osteopetrotic mutations has emerged the hypothesis that each is unique with respect to mechanisms whereby osteoclast development and/or function are reduced. The osteopetrotic (op) mutation in the rat was discovered in Fatty/ORL stock over a decade ago. The paucity of data about osteoclast biology in this mutation prompted this study of cytological, cytochemical, and ultrastructural features of osteoclasts. In op rats, osteoclasts are significantly reduced in number, but are larger and more vacuolated than in normal littermates. Mutant osteoclasts can form ruffled borders and clear zones, but their ability to fragment and excavate bone surfaces is greatly impaired. Cytoplasmic vacuoles in op osteoclasts are randomly distributed and greatly enlarged, and they stain weakly for two cytochemical characteristics of osteoclasts, tartrate-resistant acid phosphatase and acid ATPase. These findings suggest that an abnormality in the lysosomal/vacuolar system, an important component of the resorptive mechanism, may be involved in the interception of osteoclast function in this mutation. PMID- 2589218 TI - Ultrastructural morphometric analysis of cultured neonatal and adult rat ventricular cardiac muscle cells. AB - Neonatal and adult rat ventricular cardiac muscle cells cultured on laminin differed from similar myocytes grown on plastic in the amount and distribution of their mitochondria and transverse tubules. Point-count morphometry was used at the electron microscopic level to quantify these differences. Adult myocytes grown on laminin contained more mitochondria per unit volume than adult myocytes grown on plastic. No significant differences were observed in the volume percent of myofibrils in either adult or neonatal ventricular myocytes when grown on laminin and compared to those grown on plastic. The transverse tubule system in neonatal and adult myocytes was reduced significantly when both groups were cultured on laminin. Furthermore, neonatal and adult myocytes cultured on laminin were flatter than those cultured on plastic. This may indicate a relationship between the surface/volume ratio and transverse tubule development in cultured myocytes. These studies establish that point-count morphometry can be used to quantify changes in the organelle volume densities of cultured cardiac muscle cells. PMID- 2589220 TI - Eosinophils and mast cell homogeneity of the guinea pig eyelid skin, conjunctiva, and ileum. AB - Mast cell heterogeneity has been described on the basis of differential staining reactions, light microscopic morphology, anatomic location, degranulation after polyamines, biochemical contents, growth requirements, and reactions to lymphokines. We have demonstrated typical "connective-tissue mast cells" by using anatomic criteria, histological staining reactions, electron microscopy, and reaction to compound 48/80 in the guinea pig conjunctiva, eyelid skin, and ileum. A second, much larger population of cells in the ileal mucosa and the conjunctiva, and rarely in the eyelid skin stained reddish-blue with acid toluidine blue in tissue fixed in ethanol-acetate-lead subacetate (BLA) and with alkaline Giemsa in formaldehyde-fixed tissue, did not stain with ethanolic or acid toluidine blue in formaldehyde-fixed tissue or with alkaline Giemsa in BLA fixed tissue, and did not degranulate after 48/80 treatment. These are features of the rat intestinal "mucosal mast cells"; however, ultrastructural and light microscopic studies with the orcein Giemsa stain demonstrated these cells in the guinea pig to be eosinophils. Tissue culture, biochemical, and immunological studies indicate the existence of a second type of mast cell (bone-marrow-derived mast cell), ultrastructurally almost indistinguishable from the connective tissue mast cell. Our studies demonstrate only one mast cell type in the guinea pig and support the contention that other forms of mast cells are immature forms or variants of the connective-tissue mast cell. PMID- 2589219 TI - Condensation of hypertrophic chondrocytes at the chondro-osseous junction of growth plate cartilage in Yucatan swine: relationship to long bone growth. AB - Chondrocytes of the cartilaginous growth plate are found in a spatial gradient of cellular differentiation beginning with cellular proliferation and ending with cellular hypertrophy. Although it is recognized that both proliferation and hypertrophy contribute significantly to overall bone growth, mechanisms acting on the chondrocyte to control the timing, the rate, and the extent of hypertrophy are poorly understood. Similarly, mechanisms acting on the terminal chondrocyte to cause its death at the chondro-osseous junction have not been investigated. In this study we examine the condensation of terminal hypertrophic chondrocytes in proximal and distal radial growth plates of Yucatan swine at 4 weeks of age. The animals were raised in a controlled environment where activity and feeding patterns were synchronized to a given time in the light/dark cycle. We analyzed cellular condensation both as a function of circadian rhythms in a 24-hr time period, and as a function of overall rate of growth. The data suggest that the magnitude of circadian influences on long bone growth is significantly damped at the level of the hypertrophic chondrocyte compared to that seen by previous investigators studying circadian influences on chondrocytic proliferation. Secondly, the condensation of hypertrophic chondrocytes at the chondro-osseous junction varies inversely with rate of growth in length of the bone. At any time period, a higher percentage of terminal chondrocytes in the condensed form was found in the slower-growing of the two growth plates. We relate these findings to current hypotheses concerning controls of chondrocytic hypertrophy and possible controls over the timing of hypertrophic cell death. PMID- 2589221 TI - Covalent affinity labeling, radioautography, and immunocytochemistry localize the glucocorticoid receptor in rat testicular Leydig cells. AB - The presence and distribution of glucocorticoid receptors in the rat testis were examined by using 2 approaches: in vivo quantitative radioautography and immunocytochemistry. Radioautographic localization was made possible through the availability of a glucocorticoid receptor affinity label, dexamethasone 21 mesylate, which binds covalently to the glucocorticoid receptor, thereby preventing dissociation of the steroid-receptor complex. Adrenalectomized adult rats were injected with a tritiated (3H) form of this steroid into the testis and the tissue was processed for light-microscope radioautography. Silver grains were observed primarily over the Leydig cells of the interstitial space and to a lesser extent, over the cellular layers which make up the seminiferous epithelium, with no one cell type showing preferential labeling. To determine the specificity of the labeling, a 25- or 50-fold excess of unlabeled dexamethasone was injected simultaneously with the same dose of (3H)-dexamethasone 21-mesylate. In these control experiments, a marked reduction in label intensity was noted over the Leydig as well as tubular cells. Endocytic macrophages of the interstitium were non-specifically labeled, indicating uptake of the ligand possibly by fluid-phase endocytosis. A quantitative analysis of the label confirmed the presence of statistically significant numbers of specific binding sites for glucocorticoids in both Leydig cells and the cellular layers of the seminiferous epithelium; 86% of the label was found over Leydig cells, and only 14% over the cells of the seminiferous epithelium. These binding data were confirmed by light-microscope immunocytochemistry using a monoclonal antibody to the glucocorticoid receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589222 TI - Innervation of the renal proximal convoluted tubule of the rat. AB - Experimental data suggest the proximal tubule as a major site of neurogenic influence on tubular function. The functional and anatomical axial heterogeneity of the proximal tubule prompted this study of the distribution of innervation sites along the early, mid, and late proximal convoluted tubule (PCT) of the rat. Serial section autoradiograms, with tritiated norepinephrine serving as a marker for monoaminergic nerves, were used in this study. Freehand clay models and graphic reconstructions of proximal tubules permitted a rough estimation of the location of the innervation sites along the PCT. In the subcapsular nephrons, the early PCT (first third) was devoid of innervation sites with most of the innervation occurring in the mid (middle third) and in the late (last third) PCT. Innervation sites were found in the early PCT in nephrons located deeper in the cortex. In juxtamedullary nephrons, innervation sites could be observed on the PCT as it left the glomerulus. This gradient of PCT innervation can be explained by the different tubulovascular relationships of nephrons at different levels of the cortex. The absence of innervation sites in the early PCT of subcapsular nephrons suggests that any influence of the renal nerves on the early PCT might be due to an effect of neurotransmitter released from renal nerves reaching the early PCT via the interstitium and/or capillaries. PMID- 2589224 TI - Crypt base columnar cells in ileum of BDF1 male mice--their numbers and some features of their proliferation. AB - Some features of the proliferative cells at the bottom of the ileal crypts in BDF1 mice have been studied in relation to the distribution of Paneth cells (PC) in an attempt to clarify the nature and function of these crypt base columnar cells (BCC) and to elucidate some aspects of the role of the microenvironment created by the PC. Longitudinal sections of crypts have shown that the ratio of PC to the BCC, which are scattered amongst the PC, is 2.7:1 in sections or approximately 29 PC and 9 BCC per whole crypt, i.e., a ratio of 3.2:1. The labelling index of BCC is about 35%, which is comparable to that of mid-crypt columnar cells. Although the BCC do become labeled, it is concluded that they cannot create vertical pairs or runs of several adjacent BCC since this would seriously disturb the distribution of Paneth cells. Only in dividing crypts are such runs (consisting of 3 to 5 cells) observed. The ability of BCC to synthesize DNA is not dependent on their position in the Paneth cell zone. In 95% of the crypts, the highest Paneth cell is below the 7th cell position from the bottom of the crypt, and the positions of the highest PC on either side of a given crypt are similar. The secreted granules or the cytoplasm of PC specifically bind pokeweed lectin, and this can be used for identification. Tracer doses of 3HTdR (37 kBq/gm body weight) result in the histological death of some BCC, and these damaged cells are evenly distributed throughout the Paneth cell zone. These tracer doses are somewhat selectively incorporated into BCC, i.e., the BCC have a higher grain count in autoradiographs, probably because they possess more thymidine kinase enzyme activity. This ability is very sensitive to the withdrawal of food, because 24 hr of fasting abolished the observed gradient in the intensity of labelling, which is very well correlated with the distribution of BCC. Regeneration of the crypts following cytotoxic exposure to Ara-C is initiated at the base of the crypt and hence may involve the BCC with possible help from the Paneth cells. The latter are insensitive to cytotoxic (S phase specific) agents and may help in the regeneration by preserving the architecture of the base of the crypt. PMID- 2589223 TI - Postnatal development of vascularity in the inferior colliculus of the young rat. AB - The inferior colliculus in the rat midbrain is an auditory relay center whose functional maturation occurs postnatally. We examined by morphometry the vascularity and the nuclear profile density of the inferior colliculus in normal young rats at different ages (before and after the onset of auditory input). We also compared this region with a frontal region of the cerebral cortex in 24-day old rats. The inferior colliculus from aldehyde-perfused Sprague-Dawley rats aged 5, 9, 14, and 24 days was analyzed by light microscopy of semithin plastic sections. The central region (mostly the central nucleus) was sampled at 5 levels representing its entire rostrocaudal extent. Patent-blood-vessel profiles were counted and classified according to their size and profile orientation. Counts of nuclear profiles in the same sections were also made. In the inferior colliculus of rats between 5 and 24 days of age, the small (less than 10-microns diameter) cross-sectioned vessel profiles increased over 6-fold in number per unit area. Correspondingly the vascular volume density, estimated by differential point counting, increased between these ages. However, there was a decrease in the number of neuronal and glial nuclear profiles per unit area, probably because of growth in the volume of the neuronal perikarya and processes, along with cell emigration reported to occur at early postnatal ages. This study has shown that an increase in vascularity in the central region of the rat inferior colliculus continues for up to 2 weeks after the onset of hearing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589225 TI - Distribution of endogenous albumin across the rat aortic wall as revealed by quantitative immunocytochemistry. AB - Endogenous albumin was revealed over thin sections of rat aortic wall, with high resolution and specificity, by applying the protein A-gold immunocytochemical technique. Gold particles, revealing albumin antigenic sites, were observed over plasmalemmal vesicles in endothelial cells and over the interstitial space throughout the thickness of the aortic wall. The distribution of the labeling in the interstitial space varied from region to region and was associated with the collagen fibers, following the orientation of the bundles. The morphometric evaluation of this labeling demonstrated a first peak in labeling intensity in the intima followed by a steep decrease with low levels in the media, and an increasing gradient towards the adventitia. In the subendothelium, a moderate labeling was observed at the base of the endothelial cells of both aortic and capillary endothelia, followed by a decreasing gradient. Ratios between the labeling density in the intima as well as in the adventitia and that in the capillary lumen (plasma albumin) revealed different concentrations of albumin in these compartments. Endogenous albumin, under steady-state conditions, is thus unevenly distributed over the interstitial spaces across the rat aortic wall, and appears associated along the collagen fibers. PMID- 2589226 TI - Diameter increase of collagen fibrils of the mouse endometrium during decidualization. AB - The diameter of collagen fibrils was measured in different regions of the antimesometrial endometrium of mice on days 5, 6, and 7 of pregnancy as well as in the endometrium of virgin mice. The average diameter of fibrils of virgin mice was 39.18 nm (range: 20-80). In the region of fully decidualized cells, the averages and ranges were 45.32 nm (30-170), 89.39 nm (30-270), and 125.88 nm (20 370), respectively, on days 5, 6, and 7 of pregnancy. Thick fibrils larger than 70 nm had irregular profiles. Our results show that the increase in diameter is associated with the decidualization of the mouse endometrium. PMID- 2589227 TI - Advanced cervical cancer therapy: concurrent radiation therapy and cisplatin chemotherapy for advanced cervical cancer--a toxicity report. AB - It is estimated that in 1988 there will be 12,900 cancers of the uterine cervix, representing 2.6% of cancers in women. Radiation therapy has been the primary mode of therapy/palliation; for the past 15-20 years survival results achieved with radiotherapy have plateaued. Attempts have been made to find agents to use with radiation aimed at decreasing recurrence and increasing survival. Phase II studies suggest cisplatin may be an excellent agent to combine with radiotherapy. This study was performed to evaluate the toxicity of this combination. Between December 10, 1980, and August 29, 1986, nine patients with advanced cervical cancer and poor prognosis and one patient with recurrent disease were enrolled. The Gynecologic Oncology Group (GOG) criteria for adverse effects were used in this study. Hematologic, gastrointestinal, genitourinary, and skin parameters were examined. Most adverse criteria had a score of 2 or less. Grade 2 nausea/vomiting was the most frequent problem. Anemia was the next most frequent and was the most serious problem encountered. Overall, the toxicity was acceptable; therefore it seems appropriate to proceed to larger studies to evaluate efficacy. PMID- 2589228 TI - Impact of administration-related factors on outcome of adjuvant chemotherapy for primary breast cancer. AB - The survival of 229 patients treated with adjuvant i.v. cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) after surgery for primary breast cancer was analyzed according to three administration-related factors: total number of cycles received, time elapsed between surgery and start of chemotherapy, and dose intensity of treatment. All parameters were found to be significantly associated with survival of patients in a univariate analysis. Multivariate analysis confirmed the independent prognostic importance of dose intensity and time between surgery and chemotherapy. Although prospective studies are needed to confirm such results, clinicians should be aware that unnecessary treatment delays or dose reductions in adjuvant chemotherapy for breast cancer are probably detrimental to patient survival. PMID- 2589229 TI - A phase I/II trial of 5-fluorouracil and etoposide in metastatic colorectal carcinoma. AB - Twenty-two patients with metastatic colorectal carcinoma were treated in a Phase I-II study of combination therapy with 5-fluorouracil (5-FU) and etoposide (VP 16). Treatment consisted of weekly intravenous VP-16, 100-120 mg/M2, followed by 5-FU, 400-480 mg/M2, in 28-day cycles. Myelosuppression was the dose-limiting toxicity with a mean nadir leukocyte count of 3,600/mm3 and a mean nadir thrombocyte count of 101,000/mm3. There were no episodes of sepsis or bleeding. The tolerable dose for this regimen is VP-16, 110 mg/M2, and 5-FU, 440 mg/M2, weekly. A total of 63 cycles of chemotherapy were given. Although 10 patients had stabilization of disease, no partial or complete responses were documented. We conclude that there is no clinical support for the in vitro synergy observed with this combination. Further trials of this combination using this schedule in colorectal carcinoma are not indicated. PMID- 2589230 TI - Combination chemotherapy with cytosine arabinoside (Ara-C) and cis diamminedichloroplatinum (CDDP) for squamous cancers of the upper aerodigestive tract. AB - Based on the demonstration of in vitro and in vivo synergy between cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (CDDP), we designed a Phase II trial of Ara-C plus CDDP for patients with advanced squamous cancers of the head and neck and esophagus. Sixteen patients were treated on a unique schedule of continuous-infusion Ara-C, 30 mg/m2/day over 72 h, plus CDDP, 30 mg/m2/day at hours 12, 36, and 60 of the Ara-C infusion. The objective response rate was 38% (95% confidence limits 14-62%), with two patients achieving complete clinical and radiographic response (9 and 27+ months duration) and four partial responses (median duration 4 months, range 1-7 months). There was no CDDP-related nephro- or neurotoxicities, but a flu-like syndrome of anorexia and asthenia was common. Myelosuppression was the dose-limiting toxicity, necessitating Ara-C dose adjustments in 11 cycles of therapy and leading to fatal sepsis in one patient. We conclude that the activity of this combination, though comparable to that of other CDDP-containing regimens, offers no significant therapeutic advantage, and given the excessive hematologic toxicity, should not be investigated further. PMID- 2589231 TI - A pilot study of short-course, high-dose cytosine arabinoside, etoposide, and cisplatin in refractory, aggressive-histology, non-Hodgkin's lymphomas. AB - Twenty-three patients with refractory, aggressive-histology, non-Hodgkin's lymphomas were treated with cytosine arabinoside (2.0 g/m2 i.v. every 12 h on days 1 and 2), etoposide (100 mg/m2 i.v. on days 1 and 2), and cisplatin (35 mg/m2 i.v. on days 1 and 2) every 3 weeks. All patients had received one or two prior chemotherapy regimens. Five of 19 (26%) evaluable patients responded, with a median duration of response of 9 weeks (90% confidence interval: 11-48%). One patient with a complete response remains free of disease over 31 months after completing six cycles of therapy. Six transient responses of less than 1-month duration were also observed. Hematological toxicity was significant: 73% of patients experienced grade 4 neutropenia, and 52% experienced grade 4 thrombocytopenia. Twenty patients (87%) underwent dose reductions following their first cycle of therapy for grade 3 or 4 myelosuppression. We conclude that this combination of drugs, when administered by this schedule, has limited antitumor activity; however, administering the regimen with a dose-intense schedule appears warranted. PMID- 2589232 TI - Phase II evaluation of bisantrene in acute leukemia. A Southwest Oncology Group Study. AB - Twenty-nine patients with heavily pretreated acute leukemia in relapse were treated with bisantrene (maximum dose 120 mg/m2/day x 5) in a phase II study. Twenty-seven of the 29 patients were evaluable for response, receiving a total of 53 courses of treatment. There were three complete remissions (11%) lasting 27, 107, and 115 days. One brief partial remission of 43 days was also seen for a total response rate of 15%. Toxicity was mainly limited to the expected myelotoxicity with minimal nonhematologic toxicity seen. Although the complete remission rate is low, an antileukemic effect was seen in the majority of the patients treated. Sixty-one percent of the patients had at least a 50% decrease in the circulating blast count and 32% had at least a 50% decrease in the number of bone marrow blasts. We conclude that bisantrene does have an antileukemic effect, but that the optimal starting dose is not yet established. PMID- 2589234 TI - "Clinical alert" revisited. PMID- 2589233 TI - Effective control of CMF-related emesis with high-dose dexamethasone: results of a double-blind crossover trial with metoclopramide and placebo. AB - To establish the antiemetic activity of both dexamethasone (DXM) and metoclopramide (MCP) in patients receiving i.v. cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), 25 women with stage II breast cancer were entered into this study. A randomized, double-blind, crossover design was employed to evaluate DXM (24 mg in 5 doses) versus MCP (1 mg/kg as a single dose) versus a combination of both drugs (as above) or placebo (PLC). The patients were requested to complete a questionnaire evaluating the antiemetic effect. All but one patient completed the planned antiemetic program during the first four CMF courses. As compared to PLC, both the DXM-MCP combination and DXM alone provided a higher complete antiemetic protection rate (p = 0.01 and p = 0.006, respectively). The DXM regimens were more effective than both PLC (p = 0.004 and p = 0.01) and MCP (p = 0.002 and p = 0.006) in reducing the prevalence of severe vomiting. As compared to MCP, the DXM regimens provided a better control of the nausea (p less than 0.04 and p less than 0.01) and reduced both the episodes and the duration of vomiting (p less than 0.02 and p less than 0.05). The DXM regimens were also associated with a better patient opinion than the PLC (p less than 0.002 and p less than 0.0002). No significant differences were found between MCP and PLC, nor between the DXM regimens. Except for two dystonic reactions, MCP-related toxicity was mild, whereas that induced by DXM was negligible in patients with no contraindications to corticosteroids. As employed in this study, DXM provided safe and effective antiemetic protection for patients receiving adjuvant i.v. CMF. Data available do not support the use of a short-course MCP, either alone or in combination with DXM. The search for better antiemetic treatments is mandatory, especially for patients receiving adjuvant chemotherapy. To date, we recommend the use of DXM as a standard regimen and as a control for further studies. PMID- 2589235 TI - The pharmacological and pathological studies on several hepatic protective crude drugs from Taiwan (II). AB - Four crude drug extracts of Solanum incanum (entire plant), Ixeris chinensis (entire plant), Gardenia jasminoides (wild and cultivated, fructus) were administered to rats as dose of 1.0 g/kg, I.P. injection to screen the liver protective effect on CC14 induced hepatotoxicity. The acute increase of transaminase SGOT and SGPT levels that was caused by CC14 (1.0 ml/kg) S.C. injection can be significantly improved when treated with Solanum incanum (p less than 0.005), Ixeris chinensis (p less than 0.001), Gardenia jasminoides (cultivated) (p less than 0.005) but only a moderate change was shown by means of wild Gardenia jasminoides (p less than 0.05). As our results indicated, the extraction of these drugs has been found to possess a marked hepatic protective effect. The hepatic fatty metamorphosis and necrosis of central lobule were obviously improved by S. incanum and I. chinensis, administration, while the effect of treatment with G. jasminoides (cultivated) demonstrated a moderate protective action and little histopathological change by G. jasminoides (wild). In contrast to B. chinese, which has been reported previously as a treatment criteria, the S. incanum (p less than 0.01) and I. chinensis (p less than 0.01) in the present study have indicated that a significantly different hepatic protective effect on CC14 induced hepatic injury. PMID- 2589236 TI - Gastroprotective activity of ginger zingiber officinale rosc., in albino rats. AB - The cytoprotective and gastric anti-ulcer studies of ginger have been carried out in albino rats. Cytodestruction was produced by 80% ethanol, 0.6M HC1, 0.2M NaOH and 25% NaCl. Whereas gastric ulcers were produced by ulcerogenic agents including indomethacin, aspirin and reserpine, beside hypothermic restraint stress and by pylorus ligated Shay rat technique. The results of this study demonstrate that the extract in the dose of 500 mg/kg orally exert highly significant cytoprotection against 80% ethanol, 0.6M HC1, 0.2M NaOH and 25% NaCl induced gastric lesions. The extract also prevented the occurrence of gastric ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs) and hypothermic restraint stress. These observations suggest cytoprotective and anti-ulcerogenic effect of the ginger. PMID- 2589237 TI - Studies on herbal aphrodisiacs used in Arab system of medicine. AB - Toxicity studies were conducted on Brassica rapa, Prunus amygdalus and Zingiber officinale, used as aphrodisiacs in Arab Medicine. During acute toxicity test observations were made for 24 h where all these plants showed no toxicity. The animals were treated for 3 months in chronic treatment. External morphological changes, visceral toxicity, haematological changes, effects on average body weight, vital organ weight, sperm contents, sperm motility and sperm abnormalities were recorded. The average body weight increase was significant in B. rapa and P. amygdalus treated animals. Haematological studies revealed reduction in WBC level in these groups. These changes were not significant in Z. officinale treated animals. In all three groups the visceral condition was normal and the percent lethality was insignificant as compared to the control. All these plant extracts significantly increased the sperm motility and sperm contents in the epididymides and vas deferens without producing any spermatotoxic effect. PMID- 2589239 TI - The identification of pyrrolizidine alkaloid-containing plants--a study on 20 herbs of the Compositae family. AB - Twenty Chinese medicinal herbs of the Compositae family were investigated for the presence of pyrrolizidine alkaloid. Of these, only the Eupatorium species were shown to contain pyrrolizidine alkaloid. The amount present was found to vary with species, parts of the plant used, purchase sources and extraction methods. Possible toxicity from the use of these herbs is discussed. PMID- 2589238 TI - Effect of motherwort on blood hyperviscosity. AB - The effect of motherwort (Leorunus Heterophyllus Sweet, MW) on blood hyperviscosity was investigated in 105 patients. The experimental and clinical study indicated that MW has a favorable clinical impact and an effective improvement of hemorheology. MW 10 ml (5g/ml) in 250 ml of 5% glucose was given intravenously daily for 15 days. 94.5% of cases showed improvements in the form of a decrease in blood viscosity and in fibrinogen volume and an increase in the deformability of Rbc, a shorting of the time of Rbc electrophoresis and an increase in antiplatelet aggregation. PMID- 2589240 TI - Tibetan medicine Part IV: Pulse diagnosis in Tibetan medicine. PMID- 2589241 TI - Psychosomatic correlations in chronic pain patients using electroacupuncture. AB - Different reports on the efficacy of electroacupuncture in pain led to a randomized prospective study on 120 patients suffering from long-term chronic pain syndromes of different aetiology taking into account the psychological situation. The collected data included measuring the pulse amplitude difference of the arteria radialis dextra and sinistra oscillographically, pain evaluation by visual analogue scales, blood pressure and heart frequency and psychometrie. Results show that neurotic patients have a higher level of anxiety and that reduction of pain and the equalization of the amplitudes of both arterial curves is higher in anxious patients. The results are highly significant with an alpha value of 0.001. PMID- 2589242 TI - Effect of acupuncture on immunoglobulins of serum, saliva and gingival sulcus fluid. AB - The present research is a preliminary investigation of the changes of immunoglobulins in serum, saliva and gingival sulcus fluid in response to acute and chronic acupuncture stimulation in 70 volunteers. The acute effect of acupuncture showed that 30 minutes and 24 hours after acupuncture treatment saliva IgA levels were significantly increased in those who had previous low levels of IgA, but decreased in those who had previous high levels. When acupuncture was given daily for 2 weeks, the saliva IgA level was significantly increased, about 20% higher than that of the initial value. The IgG levels in serum and gingival sulcus fluid were decreased at 30 minutes after acupuncture treatment. On the other hand, chronic acupuncture stimulation (daily for 7-10 days) significantly increased IgG levels in both serum and gingival sulcus fluid. The regulatory effect of acupuncture on the immunological function of body defense system is discussed. PMID- 2589243 TI - The hypoglycemic effect of the crude drug prescription resources from Taiwan on experimental diabetic-mellitus (II)--the antihyperglycemic effect of tang-niao tung no. 2 and no. 3. AB - The water extracts of crude drugs of Taiwan Tang-Niao-Tung (T.N.T.) No. 2 and No. 3 were administered to normal and diabetic rats for investigating the antihyperglycemic effect of these two prescriptions. It was found that the blood glucose level in normal rats was temporarily increased after T.N.T. No. 2 and No. 3 administration; this may be caused by the starch content of the drugs component. In contrast, the diabetic rats have shown a significant decrease (P less than 0.01) of blood glucose in 2, 4, 6 hours after T.N.T. No. 2 and No. 3 have been given. The blood glucose percentage at 6 hours was 78.1% of T.N.T. No. 2 and 79.2% of T.N.T. No. 3 as compared to the original level. The hypoglycemic effect of T.N.T. No. 2 and No. 3 on alloxan-induced diabetic rats have suggested that action mechanism might not mediate through the release of insulin or positive feedback of glucose to insulin, neither acted on insulin receptor. It might be possible by the indirect promoting of enzyme activity. However, the pharmacological effect of some drugs could elucidate the hypoglycemic action of these prescriptions. Temporary promotion of blood glucose in normal rats will decline to normal level by 12 hours after T.N.T. No. 2 and No. 3 administration. The pharmacological effect of these herb prescriptions for diabetic rats is valuable for further study. PMID- 2589244 TI - Incomplete intestinal metaplasia in the diagnosis of columnar lined esophagus (Barrett's esophagus). AB - To investigate the distribution and specificity of intestinal metaplasia (IM) in columnar lined esophagus (CLE), the authors reviewed biopsies of the hiatal hernia pouch (HHP) and esophagus from 17 patients with CLE (84 biopsies) and 10 controls (25 biopsies). The proximal margin of the gastric folds was used as an endoscopic landmark, corresponding to the gastroesophageal muscular junction (GEMJ). No biopsies obtained above the GEMJ in control patients showed columnar mucosa. No goblet cell metaplasia was seen in 21 biopsies of the HHP from patients with CLE or in 13 corresponding biopsies from controls. In contrast, alcian blue (AB) stains showed diffuse acid mucins in 3 of 21 biopsies of the HHP from patients with CLE and in 10 of 13 corresponding biopsies from controls, demonstrating that goblet cell metaplasia clearly distinguishes biopsies of CLE from the HHP (P less than 0.01), whereas small amounts of diffuse acid mucin on AB stains do not. IM evidenced by goblet cell metaplasia was frequently seen in biopsies only 2-3 cm above the GEMJ, and CLE was limited to that area in three patients, suggesting that the distal esophagus cannot be dismissed as a site for metaplastic and possibly premalignant mucosa. Adenocarcinoma was diagnosed during the course of the study in one patient with only 5 cm of columnar mucosa above the GEMJ. PMID- 2589245 TI - Cytoferrin, maternofetal iron transport, and neonatal hemochromatosis. AB - The serum concentration of cytoferrin, a low-molecular-weight iron-binding compound, in an infant with neonatal hemochromatosis was significantly elevated (270X) by comparison with normal adult values. Concentrations of cytoferrin in cord sera from 25 normal term neonates were substantially lower but also were elevated (2X) by comparison with normal adult values. Concentrations of cytoferrin in placental tissues were comparable to values previously obtained for various mammalian tissues, and concentrations of cytoferrin in maternal sera were not elevated. This transplacental gradient in serum concentrations of cytoferrin suggests that cytoferrin may be involved in maternofetal iron transport. Although iron is known to be taken up by the hemochorial placenta via trophoblast brush border receptors for transferrin, further iron handling within the placenta is poorly understood. In particular, the routes or carriers by which iron enters the fetal circulation have not been identified. Cytoferrin may participate in stages of maternofetal iron transport distal to transferrin, and further investigation of the role of cytoferrin in neonatal hemochromatosis and other disorders may be warranted. PMID- 2589246 TI - Whole blood aggregation using impedance and particle counter methods. AB - Platelet function in platelet-rich plasma may be evaluated using an optical or electrical impedance method. Platelet function in whole blood may be studied using an impedance or particle counter method. A comparison of these techniques in whole blood has not been performed. Twenty-four healthy subjects were studied using both techniques over a range of concentrations of collagen and adenosine diphosphate (ADP). Although broad similarities exist, discordant patterns occur in individual subjects. The particle counter method is capable of detecting small aggregates and thus is more sensitive. The impedance aggregometer detects only larger aggregate formation. These techniques are complementary rather than competitive and may have considerable potential in profiling platelet function. PMID- 2589247 TI - Primary malignant melanoma of the esophagus with diffuse melanocytic atypia and melanoma in situ. AB - Primary malignant melanoma is an unusual lesion in the esophagus that is not infrequently seen in association with melanosis. A case of esophageal invasive malignant melanoma with melanosis is described in which the melanosis exhibited melanocytic atypia extending through to melanoma in situ. The authors know of no previously reported such finding. PMID- 2589248 TI - Massive retroperitoneal angiomyolipoma. A lesion that may be confused with well differentiated liposarcoma. AB - A benign massive retroperitoneal lipomatous tumor is described. The tumor, from a 72-year-old woman with increasing abdominal girth, consisted of a mixture of mature lipocytes, smooth muscle cells, and thick-walled medium-size blood vessels. Although the tumor focally involved the uterine serosa, suggesting the possible diagnosis of uterine leiomyoma with fatty change, the authors think that, because the bulk of the tumor was located in the retroperitoneum and because the tumor contained characteristic thick-walled blood vessels from which smooth muscle cells radiated, this tumor would be best classified as a retroperitoneal angiomyolipoma. Although both angiomyolipomas and leiomyomas with fatty change presenting as large retroperitoneal tumors are rare, and therefore are not well-recognized by surgical pathologists, they are benign and must be distinguished from liposarcomas. PMID- 2589249 TI - Amyloid goiter and arthritides after kidney transplantation in a patient with systemic amyloidosis and Muckle-Wells syndrome. AB - A case of hereditary AA amyloidosis with Muckle-Wells syndrome is described. After a successful kidney transplantation for chronic renal failure due to renal amyloid deposits at age 21, the patient, a white female now 26 years of age, developed a large amyloid goiter as a manifestation of the systemic amyloidosis and recurrent monarthritides. Both observations are novel for this disease. Subtotal thyroidectomy and oral colchicine administration, known to be effective in preventing complications of familial Mediterranean fever, another hereditary type of AA amyloidosis, proved highly effective in the management of this unusual case. PMID- 2589250 TI - Solitary bone cyst of the radius containing Liesegang's rings. AB - The authors describe the case of a 33-year-old man with a solitary cystic lesion of the left distal radius with central radiodensities that radiographically suggested a chondroid matrix. Curettage of the lesion revealed numerous calcospherites with a lamellar structure. This lamellar pattern is thought to be a result of alternating precipitation and diffusion of supersaturated solutions. This biochemical process has been called the Liesegang's phenomenon, and the structures have been termed Liesegang's rings. The presence of these structures in this benign lesion contributed to atypical roentgenographic and pathologic findings. PMID- 2589251 TI - Soft tissue cysticercosis. Diagnosis by fine-needle aspiration. AB - Taenia solium infection is endemic in Asia and cysticercosis is not uncommon. The authors report a case of cysticercosis diagnosed by fine needle aspiration using a cell block. The authors believe it to be the first such case so diagnosed. PMID- 2589252 TI - Quality assurance in diagnostic immunohistochemistry. A discipline coming of age. PMID- 2589254 TI - More on orthognathic surgery. PMID- 2589253 TI - Re: Retention--retainers may be forever. PMID- 2589255 TI - Clinical experience with third molar orthodontics. AB - An orthodontic uprighting technique for effective treatment of impacted third molars, exposed or unexposed, is described. When used with conventional fixed appliances, this technique presents a viable option to extraction or prediction of eruption. Several applications illustrate that, with proper intervention, this uprighting technique is simple and effective in positioning malposed third molars. PMID- 2589256 TI - The prevalence of orthodontic extractions. AB - The controversy regarding extractions for orthodontic treatment continues and today is invoked by some as a feature of the "standard of care." For this and other reasons, it is necessary to have contemporary data on the general prevalence of orthodontic extractions and the interpractice range of extraction rates in current specialty practice and, if possible, also to establish possible reasons for, and consequences of, the extraction versus nonextraction decision. Although all treatment decisions are made on a case-by-case basis, practitioners appear to have personal preferences for or against extractions and hence adopt policies with different degrees of aversion to or bias toward extraction therapy. A number of factors enter into the extraction decision. These include features of the malocclusion, objectives of treatment, and the technique selected to accomplish desired results. The present study does not address such issues but merely serves to provide epidemiologic data to estimate extraction frequency in contemporary orthodontic practice. Accordingly, a telephone survey of all licensed orthodontists in Michigan was conducted to determine their subjective estimates of extraction rates for patients in their practices. There were 238 respondents, for a response rate of 90.2%. Reported rates range from 5% to 87%. We then selected five practices from the extremes of the reported extraction rates. Three practices from the high end and two from the low end were included for an examination of patient records. Records of a total of 438 patient whose treatment had been completed were reviewed. The actual extraction rates for these practices ranged from 25% to 85%, which differed considerably from the clinicians' subjective estimates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589257 TI - An evaluation of the changes in soft-tissue profile form induced by orthodontic therapy. AB - In view of the growing concensus that traditional cephalometric appraisals yield data of dubious scientific value, the changes in soft-tissue profile forms were evaluated by an alternative technique. This involved dividing the soft-tissue profile form into a series of triangular finite elements spanning homologous datum points. With the use of techniques derived from continuum mechanics, the changes in soft-tissue profile form were evaluated by computing the degree of distortion in each triangle after treatment (target element) compared with the triangle before treatment (reference element) in terms of specific size and shape parameters. In a comparison of samples of patients with Class I and II malocclusion, varying patterns of facial profile change were noted, depending on the parameters analyzed. The results, therefore, showed that although such techniques offer rigorous cephalometric potential, further investigation is required to identify more appropriate datum points. PMID- 2589258 TI - Does the mandible alter its functional position during activator treatment? AB - The study aimed at revealing possible changes, in activator-free periods, in the positions and movements of the mandible induced by the wearing of an activator. Twenty-one children being treated with three different types of activator for the correction of Angle Class II, Division 1 malocclusion were studied. The movement capacity of the mandible, the rest position, and the position of tooth contact during chewing were recorded with a Sirognathograph before treatment and repeatedly during the first year of treatment. With the exception of a slight increase in the maximal protrusion, no changes in mandibular movement capacity were found. The anteroposterior position of the mandible in the rest position was constant during the period of treatment, but the freeway space increased. No changes in the position of the point of tooth contact during chewing were found. The study produced no evidence of a treatment-induced forward positioning of the mandible in activator-free periods. PMID- 2589259 TI - The anterior component of occlusal force. Part 1. Measurement and distribution. AB - The purpose of this investigation was to design and develop instrumentation to measure the anterior component of occlusal force generated by a single tooth under a known axial load. An additional objective was to quantify the distribution and dissipation of this force as it progressed anteriorly. The anterior component of the occlusal force generated by the left second molar was calculated from frictional force measurements at each contact mesial to the first molars in both dental arches. The distribution of this force and its dissipation were determined for 15 subjects. When a load was placed on the posterior teeth, the anterior component of the occlusal force was found to progress anteriorly through interproximal contacts and not to progress beyond open contacts. The mean magnitude of this force for a conservative occlusal load of 20 pounds was unexpectedly high: 5 pounds against the premolars and 1 pound against the canines. In some subjects this force crossed the dental midline and continued around the arch to the canine of the contralateral side. The distribution and dissipation of the anterior component of the occlusal force anteriorly approximated an exponential decay function. PMID- 2589260 TI - Surgical orthodontic correction of mandibular deficiency by sagittal osteotomy: clinical and cephalometric analysis of 1-year data. AB - A homogeneous sample of 76 mandibular retrognathic patients (mean age, 28 years) were examined for postoperative alterations after surgical treatment by bilateral sagittal split osteotomy and mandibular advancement with wire fixation. Skeletal and dental measures were obtained from preoperative, immediate postoperative, fixation-release, and 1-year cephalograms. Spearman correlation was used as a preliminary analysis to assess the relationship between postsurgical change and age, genioplasty, amount of mandibular advancement, and preoperative mandibular plane angle. Genioplasty and amount of mandibular advancement were included as independent factors in the subsequent repeated-measures analysis of variance, since these were the only two factors that showed a consistent trend of correlations with postoperative change. Genioplasty was a significant factor in the X and Y coordinate changes in pogonion, while the amount of mandibular advancement was a significant factor in the X coordinate movements of all mandibular landmarks except gonion and condylion. The mean amount of horizontal advancement was 5.2 mm, and anterior face height increased 5.1 mm. During fixation, B point moved posteriorly (x = -1.6 mm, p less than 0.01) and inferiorly (y = 1.0 mm, p less than 0.01). After fixation release, these trends were reversed, resulting in a nonsignificant net horizontal change (x = -0.5 mm, p = 0.10) and a significant net superior movement (y = -1.3 mm, p = 0.01) by 1 year. Pogonion, menton, and mandibular incisor tip showed similar patterns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589261 TI - Changes in condyle position after bilateral vertical ramus osteotomy with and without osteosynthesis. AB - The purpose of the present study was to elucidate the importance of ramal osteosynthesis and evaluate postoperative condylar movements. The right temporomandibular joints of 53 patients with mandibular prognathism were examined by linear tomography the day before, 1 week after, and 1 year after surgery. During surgery the patients were randomly allocated to two groups: one with (n = 26) and one without (n = 27) osteosynthesis. It was found that osteosynthesis did not influence condyle position (p greater than 0.3). The two groups were thereafter pooled. Radiographic measurements of the posterior and anterior interarticular space revealed that condyle position 1 week postoperatively was forward and downward in relation to the preoperative position (posterior fossa, p less than 0.001; anterior fossa, p less than 0.01). One year later the condyle position demonstrated a tendency to approximate the preoperative position, especially with respect to the posterior part, but there was still a significant (p less than 0.01) difference when related to the original position. In conclusion, osteosynthesis after ramus osteotomy seems to be of no importance when healing and postoperative condyle position are considered. Furthermore, 1 year after surgery the condyles were not reestablished in their preoperative positions. PMID- 2589262 TI - Enamel surface abrasion from ceramic orthodontic brackets: a special case report. AB - The purpose of this report is to present a dramatic case of enamel abrasion from ceramic orthodontic appliances that was discovered only after appreciation of the initial findings of a study underway at the Department of Orthodontics, University of Minnesota. An artificial oral environment used in this study to simulate mastication also is described. The potential detrimental effects of ceramic appliances on tooth contact are discussed. All aspects of any new material should be investigated before its clinical application to prevent undesired side effects. PMID- 2589263 TI - Peripheral giant cell granuloma during orthodontic treatment. AB - Inflammatory and hyperplastic gingival responses during orthodontic treatment are common. These may complicate the actual treatment and may require periodontal therapy. The present report describes the development of an interproximal enlarged peripheral giant cell granuloma during orthodontic treatment, resulting in migration and separation of the neighboring teeth and resorption of the interproximal alveolar septum and molar root. The lesion was excised and the bone was curetted; this led to spontaneous migration of the involved teeth to their natural positions. PMID- 2589265 TI - A 1-month elective in international health for senior pediatric residents. PMID- 2589264 TI - Legal aspects of orthodontic practice: risk management concepts. Update on TMJ litigation--Part 2. PMID- 2589266 TI - Adhesive tape remover pads: a risk to the newborn? PMID- 2589267 TI - Low serum complement levels in anorexia nervosa. PMID- 2589268 TI - On combination therapy with benzoate and piridoxilate. PMID- 2589269 TI - Jejunal stenosis: a delayed complication of lap-type seat belt injury. PMID- 2589270 TI - Perinatal abnormalities and subhypothalamic bright spot on magnetic resonance imaging in pituitary dwarfs. PMID- 2589271 TI - Being just a husband is no fun. AB - One of our stalwarts on the Editorial Board has had a unique experience in the last few years; he has been a transcontinental spouse. In one of his two lives, as he so aptly describes, he has learned how the "other half" feels to be "the spouse of . . .". His article has currency, not only for the experience itself and its reflection of some marriages today, but because such experience will become commonplace in the future. More and more women have entered medicine and other professional careers and are achieving hierarchical status within their chosen fields. Their male spouses will now have to cope, as our female spouses have for decades, with a quite different role than that of the stereotypic dominant male, so prominent in American conception. My wife, Shirley, and I attended a retreat for first-year freshman medical students not too many years ago. I was privileged to be a member of the small break-out group that consisted of spouses and so-called significant others of the medical students. To my amazement and education, the majority were male (correspondingly, most of the students attending the retreat were female), and the attitudes displayed echoed what I had heard female spouses of the faculty saying for years. For example, one male businessman said, "Do you mean that if she wants to take a residency in Seattle, I'd have to give up my business and follow her? . . . Hell, no!" Perhaps he would be like Dr Stiehm and conduct a Los Angeles-Tucson-to-Seattle marriage. Another complained, "At every party we go to, all they talk about is medicine! Don't they have any other interests?" And on through the day. On reflection, Shirley and I realized that medical marriages are in for some surprises in the future. Dr Stiehm's experience is just the forerunner of many like it in the future. We will have to find new ways to make relationships work and to be sustained over the years. Men will have to learn to be secondary in interest to friends and colleagues of their successful female spouses. Men will have to learn to tolerate highly technical cocktail-party and dinner-party talk outside their sphere of knowledge, and interest, and scope. We are truly in for a brave new tomorrow. Dr Stiehm's firsthand description will be recognized by many today as pertinent and will be a blueprint for the future. May all have the wisdom and humor of Judy and Dick Stiehm! PMID- 2589272 TI - Age-related patterns of violent death, Cook County, Illinois, 1977 through 1982. AB - To clarify age-related patterns of violent death in childhood, a study was undertaken of medical examiner records concerning 437 deaths of Cook County, Illinois residents, aged younger than 15 years, who died from 1977 through 1982, and whose deaths were ruled as homicides or of an undetermined manner. Males outnumbered females after the age of 1 year. Black children were overrepresented. Perpetrators were usually parents for victims aged younger than 5 years and others for victims aged 5 years or older. Different circumstances of death characterized victims who were younger (mainly beatings) and older (mainly gunshots). Incidence was associated with urban residence and poverty, and it was highest among the youngest and oldest children. Striking differences were found in death rates for age subgroups within standard age groupings (eg, 19.77/100,000 for 1 and 2 years and 6.35/100,000 for 3 and 4 years). Different geographic areas had the highest rates for younger and older victims. We conclude: (1) Separate strategies are needed to protect the two groups at highest risk for homicide: black children aged younger than 3 years and older than 11 years in poor urban areas. (2) Standard homicide reporting practices should include narrow age groupings. (3) Age-related patterns of child homicide must be considered in the planning of prevention trials. (4) Research is needed to clarify why children of different ages are at differing risks in different communities. PMID- 2589273 TI - Firearm ownership among nonurban adolescents. AB - Firearm injury is the second leading cause of death among teenagers. In this study we examined firearm acquisition and ownership in a biracial cohort of 664 teenagers (313 male and 351 female). Ownership was prevalent among male adolescents (48%) and rare among female adolescents (4%). Among these suburban and rural teenagers, the ownership rate was highest for white male adolescents (56%). Handgun ownership was more frequent among male school dropouts (22%) than enrollees (7%). The first firearm was typically acquired by late childhood or early adolescence (median age, 12.5 years). An adult male family member (eg, father, grandfather, uncle) was the primary source. The prevalence, developmental timing, and sociodemographic correlates of firearm acquisition should be useful for informing preventive clinical practice and interventions. PMID- 2589274 TI - Prophylaxis of recurrent acute otitis media and middle-ear effusion. Comparison of amoxicillin with sulfamethoxazole and trimethoprim. AB - We compared the efficacy of amoxicillin with that of the combination drug sulfamethoxazole and trimethoprim in reducing recurrences of acute otitis media (AOM) in a single-blind, randomized, placebo-controlled trial involving 96 children. Each of the children had had three or more episodes of AOM in the preceding 6 months, and 97% (93/96) of them still had unilateral or bilateral effusion at the beginning of the study. During the 6-month study period, 9 (27%) of 33 of the children in the amoxicillin group developed 9 episodes of AOM, 9 (27%) of 33 of the children in the sulfamethoxazole and trimethoprim group experienced 11 episodes of AOM, and 19 (63%) of 30 of the children in the placebo group developed 25 episodes. Young age and day-care attendance characterized children for whom prophylaxis was more efficacious. Overall persistence of middle ear effusion was shorter in treated children only as a consequence of the reduced number of new episodes of AOM. PMID- 2589275 TI - Predictors of trough serum gentamicin concentrations in neonates. AB - Neonates admitted to an intensive care nursery frequently receive gentamicin sulfate therapy. This study was undertaken to determine predictors of an elevated (greater than or equal to 2 mg/L) trough serum concentration of gentamicin sulfate (undesirable because of potential toxic effects). A total of 140 infants with birth weight of 496 to 4545 g and gestational age of 23 to 42 weeks who received gentamicin in the first days of life were studied prospectively. The trough serum concentration of gentamicin was not significantly affected by concurrent use of dopamine hydrochloride, indomethacin, furosemide, or umbilical artery catheters. Of 11 infants weighing between 1000 and 1500 g on an 18-hour dosing interval, 55% had trough serum gentamicin concentration of 2 mg/L or more. Use of the recommended 24-hour dosing interval for infants weighing less than 1000 g and an 18-hour schedule for preterm infants weighing more than 1000 g resulted in a significant number of elevated trough serum gentamicin concentrations in the latter. A dosing interval of 24 hours for infants less than 1500 g and 18 hours in infants between 1500 and 3250 g is suggested. PMID- 2589276 TI - Clinical predictors of Chlamydia trachomatis endocervicitis in adolescent women. Looking for the right combination. AB - Chlamydial disease in adolescent women is a serious public health problem, but secondary preventive efforts through early detection and treatment are encumbered by the cost and complexity of mass screening. This study was undertaken to identify clinical predictors of infection that might narrow the scope of screening adolescent populations. Demographic/clinical data and endocervical smears for the direct-specimen fluorescein-conjugated monoclonal antibody test for Chlamydia trachomatis were collected from 244 consecutive women, 21 years of age or less, attending an adolescent health clinic. Positive direct-specimen fluorescein-conjugated monoclonal antibody test for C trachomatis results were associated with a past history of chlamydial infection, multiple sexual partners, sexual contact with men with urethritis, nonuse of condoms, metrorrhagia, exocervicitis, mucopurulent endocervical discharge, abnormal cervical cytologic features, and isolation of Neisseria gonorrhoeae from the endocervix. These variables were entered into a discriminant analysis to predict direct-specimen fluorescein-conjugated monoclonal antibody test for C trachomatis results. The discriminant function was statistically significant but explained only 17% of between-group variance. Two variables alone, exocervicitis and partners with urethritis, correctly predicted direct-specimen fluorescein-conjugated monoclonal antibody test for C trachomatis results in 79% of all cases (negative predictive value 90%; positive predictive value 35%). When routine screening with reliable laboratory tests is not feasible, selective testing or empirical treatment of adolescent women with either risk factor may be cost-effective alternatives. PMID- 2589277 TI - Lead screening at pediatric teaching programs. PMID- 2589278 TI - Regulation of oxygen concentration delivered to infants via nasal cannulas. AB - The administration of oxygen to infants via nasal cannulas is now a common practice in neonatal units although the inspired oxygen concentration reaching the patient's airway is unknown. We measured the hypopharyngeal oxygen concentration in 10 infants who were receiving oxygen via nasal cannulas and assessed the impact of changes in the flow rate and inspired oxygen concentration. Weaning these infants by reducing the flow rate, even if changes are slight, produces clinically important changes in the oxygen concentration reaching the airway. Such changes are poorly tolerated by infants with chronic lung disease. Changing the flow rate and inspired oxygen concentration, rather than the flow rate alone, provides greater precision and is likely to avoid excessive and abrupt changes in the oxygen concentration reaching the airway. PMID- 2589279 TI - Congenital cardiovascular malformations in twins and triplets from a population based study. AB - Data from the Baltimore-Washington Infant Study of congenital cardiovascular malformations permitted detailed analysis of congenital cardiovascular malformations in 62 twins and 3 triplets and 2303 singleton cases. A probability sample of controls (n = 2793) included 43 twins. The case prevalence of multiple births was 28 of 1000, compared with a 15 of 1000 prevalence among controls (chi 2 = 5.7). There were more girls among case twins than among case singletons and controls (chi 2 = 9.0). Monozygosity was no more frequent in case twins than in controls. Looping defects occurred in 4 monozygotic twin pairs compared with only 1 dizygotic twin pair. The twinning process itself may be implicated in the development of congenital cardiovascular malformations in some of these infants, especially those with looping defects, but concordance of types of defects in 4 of 65 pairs implicates genetic factors in the determination of some forms of congenital cardiovascular malformations. PMID- 2589280 TI - Nonphenylketonuric hyperphenylalaninemia. AB - Sixteen subjects with nonphenylketonuric hyperphenylalaninemia were followed up during a period of years. Dietary treatment did not seem to influence the outcome, and no relationship between blood phenylalanine and intellectual outcome was demonstrable. PMID- 2589282 TI - Radiological cases of the month. Diskitis. PMID- 2589281 TI - The adolescent heterosexual relationship and its association with the sexual and contraceptive behavior of black females. AB - We tested the hypothesis that the nature of the heterosexual relationship would be associated with the contraceptive and sexual behavior among three groups of females: those with a boyfriend who agreed to be interviewed (n = 31); those whose boyfriends refused to be interviewed (n = 38); and those without a single identifiable boyfriend (n = 44). A pretested questionnaire was administered to a random sample of 113 black females aged 12 to 18 years from a lower socioeconomic population. The three groups did not differ in age, Tanner stage, previous pregnancies, or in demographic variables. Females with boyfriends were more likely than others to be currently sexually active. Overall, 47.8% of the sample was sexually active. Females whose boyfriends were interviewed were more likely to feel that having a baby would ruin their life. Among sexually active females (n = 54), a higher percentage of females whose boyfriends were interviewed (90%) were currently using a prescription method of birth control and demonstrated higher previous contraceptive compliance. There were no differences between the groups with boyfriends in the degree that the females felt their boyfriends supported their use of birth control; those without boyfriends perceived less support. Six months after the initial interview, a higher percentage of sexually active females had a boyfriend as compared with other subjects. Although the 31 females and their boyfriends differed in the mean scores of several sexual behavior and attitude scales, the girls' and their boyfriends' scores on these scales were moderately correlated. These findings suggest that the nature of the heterosexual relationship may influence both the sexual and the contraceptive behavior of black female adolescents. PMID- 2589283 TI - Radiological cases of the month. Gastrointestinal manifestations of hemolytic uremic syndrome. PMID- 2589284 TI - Partition of nitrogen intake and excretion in low-birth-weight infants. AB - Although nitrogen balance studies have been carried out in low-birth-weight infants, few have partitioned the nitrogen into its components. In this study, 72 hour balance studies were conducted in 24 low-birth-weight infants (gestational age, 30.7 +/- 1.6 weeks; birth weight 1.36 +/- 0.25 kg) fed their mothers' milk (preterm milk) or 50% preterm milk and 50% formula. Total nitrogen, nonprotein nitrogen, and whey protein intake and excretion were measured. Total nitrogen intake (preterm milk group, 452 +/- 138 mg/kg per day; preterm + formula group, 406 +/- 93 mg/kg per day), absorption (85%), and retention (71%) were not significantly different between groups. Intact and fragments of secretory IgA and lactoferrin were detected in soluble fecal extracts, and represented 25% and 9% of intake, respectively. Feeding preterm milk allows for nitrogen accretion similar to intrauterine growth rates for 5 weeks postnatally, and provides potentially functional proteins for the low-birth-weight infant. PMID- 2589285 TI - Cardiac malformations in relatives of infants with hypoplastic left-heart syndrome. AB - In a pilot study of relatives of infants with hypoplastic left-heart syndrome (HLHS), we obtained a medical history, cardiovascular examination, and echocardiogram in 48 first-degree relatives of 11 probands with isolated HLHS and 3 with HLHS and noncardiac malformations. Echocardiography confirmed heart defects in 5 of 41 relatives of patients with isolated HLHS. In four instances, the cardiac abnormality was unrecognized. Among 7 relatives of infants with HLHS and extracardiac anomalies, no heart defects were detected. Cardiac defects occurred in first-degree relatives of probands at a frequency higher than previously predicted by an additive multifactorial model of inheritance. These findings suggest that first-degree relatives of HLHS probands may have an increased risk for subclinical cardiac defects and that genetic factors likely contribute to the cause of left-heart blood-flow lesions. PMID- 2589287 TI - Suicide by gunshot while driving an automobile. AB - Suicide by a motor vehicle occurs more commonly than is realized, and may be difficult to prove. Suicide by other means while driving a vehicle is far less common. An automobile driven by a young woman left a road at high speed, became airborne, and came to rest on its top in a front yard. This was initially assumed to be a fatal traffic accident. Upon righting the vehicle, a .357 revolver was found on the ground beside it. A single, fatal, self-inflicted gunshot wound was found in the decedent's midanterior thorax. A suicide note was found in her purse. She had been chronically depressed and had twice attempted suicide. Vehicular suicides may constitute 10-30% of fatal single-vehicle crashes, and must be considered in any vehicular mishap lacking another reasonable explanation. Suicide by other means while driving is far less common than suicidal vehicular collision and suicidal death from carbon monoxide in motor vehicles. An autopsy should be performed in each of these sometimes-low-priority single-vehicle deaths in order to certify vehicular accidents correctly; to discover and document vehicular suicides; and to detect homicides disguised as vehicular mishaps. PMID- 2589286 TI - Suicide from multiple gunshot wounds. AB - Nine cases of multiple-shot suicides (suicides involving more than two gunshot wounds) examined in the last 6 years at the Office of the Chief Medical Examiner. State of Maryland, are reported. All victims, with the exception of one, were white: three were women and six were men, with ages ranging from 22 to 81 years. For each case, the results of the scene investigation, the ammunition used, and the autopsy and toxicological findings are described. Each victim suffered 3-5 gunshot wounds. The most common site for the gunshot wounds of entrance was the precordial region, followed by the left chest, the head, and the abdomen. Gunshot wounds were rarely localized exclusively to the head, whereas gunshot wounds scattered on different classic suicide body sites or all confined to the precordial region and the left chest were common. A distinction between instantaneously lethal targets, rapidly lethal targets, and targets of secondary importance is provided, and the guidelines for the proper determination of a multiple-shot suicide are presented. PMID- 2589289 TI - Suicide by jumping from buildings. AB - A study of 82 suicides during 1982-1986 that were committed by jumping from buildings was performed using the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, U.S.A. The analysis involved the age, race, and sex of the victim along with the results of toxicologic studies and the cause of death. Additionally, the decedent's place of residence, location of the suicide, height of the building, and the reason for the suicide were investigated. Whether or not a note was left by the decedent was also ascertained. The suicidal "jumper" most commonly was a white man who was greater than 60 years of age who died from the resultant multiple injuries. The victim commonly was sober and drug free at the time of the incident. In approximately two-thirds of the cases, the location of the suicide was the victim's residence, which frequently was an apartment or condominium-type dwelling that was seven floors or higher from the ground. The victim often had experienced depression prior to the incident and did not usually leave a suicide note. This article compares the Dade County cases with others that have been studied and discusses the reasons why jumping from a building may have been chosen as the suicidal mechanism. PMID- 2589288 TI - Multiple suicidal gunshots to the head. AB - We report two cases of suicide by multiple gunshots to the head. The first victim (of two shots) fired the first shot, which was observed, into his mouth, leading to damage to the left optic nerve and frontal lobe. The man still was able to drive his car home, where he shot himself in his right temple. He died 2 days later. The second victim (of three shots) was a 58-year-old man who was found dead on his bed. Reconstruction of the case disclosed that the first shot had passed through his tongue and slightly damaged the second cervical vertebral body. He then shot himself in his right temple, leading to damage of the temporal lobe. Finally, he shot himself in his left temple, resulting in destruction of the pons. In the first case, an amateurishly modified 8-mm blank revolver firing 6.35-mm- (.25)-caliber ammunition was used; in the second case, a rifle firing 5.6-mm (.22)-caliber ammunition with a reduced charge was used. In both cases, low-energy transfer to brain tissue by the initial bullets was due to low bullet energy or due to the bullets' missing the brain or vital centers. PMID- 2589291 TI - Diagnostic angiography in postoperative autopsies. AB - Postmortem angiography was used as a diagnostic tool to rule out surgical malpractice in 227 medicolegal autopsies following postoperative deaths in Finland. Of the cases, 111 involved neurosurgical patients or patients undergoing operations on the carotid arteries, 62 involved coronary bypass patients, and 54 patients died following abdominal surgery. A portable perfusion device for postmortem angiography at the autopsy table involves attaching quick couplings to a compressed airline. Permanent cast and three-dimensional topographic assessment of vascular anatomy are achieved using solidifying silicone rubber with lead oxide as a contrast medium and stereopair radiographs. This technique can be performed by experienced autopsy technicians and can be linked to normal autopsy services. In our experience, postmortem angiography is useful in investigating all complicated deaths following surgical operations. PMID- 2589290 TI - Heart valve measurement at autopsy can distinguish cardiac from non-cardiac causes of death. AB - The circumferences of the four intact cardiac valves were measured during 397 coroner's autopsies using an obturator cone to assess the value of this measurement in the postmortem diagnosis of cardiac disease. Valve sizes of cases with cardiac and noncardiac causes of death were compared using logistic regression to assess the effects of confounding variables including sex, age, height, build and the presence of chronic obstructive airways disease. Mitral valve enlargement was found to be significantly associated with cardiac death, as were build, age, and sex. Measurement of the mitral valve at autopsy can help distinguish cardiac from noncardiac causes of death. PMID- 2589292 TI - The descriptive epidemiology of unnatural deaths in Oregon's state institutions: a 25-year (1963-1987) study. I. A preliminary analysis of recent incidence rates of suicide in mental and correctional facilities. AB - This paper presents for the first time the annual suicide incidence rates of residents from four Oregon state institutions for a 5-year (1983-1987) period of time. The suicide rate for inmate-patients of the Forensic Psychiatric Program (for the care and treatment of individuals who have been found guilty of serious crime and to be mentally ill) is 820/100,000. This represents a suicide rate 51 times higher than the rate for Marion County or the state of Oregon. This is also one of the highest annual suicide rates ever reported. The suicide rate for patients of the Oregon State Hospital is 289/100,000, which is similar to other reported suicide rates in hospitalized mentally ill populations. This rate is approximately 18 times higher than the rate for Marion County or the state of Oregon. The suicide rate for inmates of Oregon's four correctional institutions is approximately 29/100,000, which is similar to other reported rates for prisoners. This rate is approximately 1.8 times higher than the rate for Marion County or the state of Oregon. The suicide rate for residents of the Fairview Training Center (for care of the mentally retarded and developmentally disabled) is zero. PMID- 2589293 TI - Tattoos of the Marielitos. AB - Tattoos on Cuban refugees, particularly those who entered the United States during the Mariel Boatlift of 1980, have been associated with both criminal activity and religious affiliations. In an effort to understand better the significance and meanings of these tattoos, a series of interviews (initially informal, followed by a formal survey instrument) were conducted. Examples of the various tattoos were gleaned from the files of the Dade County Medical Examiner Department. In general, tattoos on Cuban refugees signify prior incarceration in Cuban prisons, usually do not reflect criminal specialization, and often reflect affiliation to Afro-Caribbean cults (especially Santeria, Palo Mayombe, and the Abakua Secret Society). In addition, many tattoos reflect the values and attitudes of Cuban jail subculture. PMID- 2589294 TI - Postmortem tricyclic antidepressant concentrations. Lethal versus nonlethal levels. AB - Evidence has accumulated that postmortem release of tissue-bound tricyclic antidepressants (TCAs) may cause falsely elevated postmortem blood levels, thus rendering it more difficult to determine if the cause of death was an overdose. This study, a review of 24 TCA-related deaths, is aimed at defining the practical significance of such a problem and providing a workable approach to interpreting postmortem TCA levels. Deaths clearly due to TCA drugs were compared with deaths that were not caused by TCA drugs, but in which the decedent's postmortem blood tested positive for TCA medications. There is little evidence that postmortem elevations in blood TCA levels cause frequent problems in differentiating lethal from nonlethal levels (overdose from nonoverdose cases). The data suggest that using a heart blood level of 0.100 mg/dl as an indicator of lethality is practical at the present time and poses little likelihood of error. Isolated cases suggest that postmortem TCA increases can occur; further work is needed in this area to clarify more fully the significance and frequency of such cases. At present, it seems prudent to utilize peripheral blood samples for TCA testing on autopsy material, if a conservative estimate of TCA concentration is desired, possibly augmented by liver TCA levels and parent-metabolite ratios if money, facilities, and time permit. PMID- 2589295 TI - Suicide by nitrous oxide poisoning. AB - Fatal nitrous oxide poisoning usually occurs accidentally during the administration of general anesthesia. It seldom occurs during autoerotic behavior or in acute drug abuse. We report an unusual case of a health professional who committed suicide by inhaling nitrous oxide. PMID- 2589296 TI - Suicide by band saw. AB - Suicidal injuries caused by power tools have rarely been reported in the literature. The case of a 37-year-old white male schizophrenic patient who sustained a fatal self-inflicted neck injury from a band saw, while engaging in occupational therapy, is presented. Unusual features of this type of injury as noted at postmortem examination were the extent of the wound, the absence of hesitation injuries, and the presence of grease wipe, bone dust, and sawdust within the wound. PMID- 2589297 TI - Nine-gunshot suicide. AB - In this article, we describe an unusual case of suicide involving nine gunshot wounds to the anterior chest. This illustrates that individuals may function for a short time with fatal wounds and stresses the importance of a complete investigation. PMID- 2589298 TI - Simultaneous temporal and frontal suicidal gunshots. AB - A white man in a remote area of Alaska shot himself simultaneously with two revolvers--a .41 magnum and a .44 magnum. Only three examples of two-gun suicides are described in the literature. PMID- 2589299 TI - Sudden infant death from atelectasis due to amniotic fluid aspiration. AB - An infant girl, whose hands showed lobster-claw deformity, was found dead in her bed at 17 days of age. Macroscopic and microscopic examination of the lungs showed fatal atelectasis. The alveolar spaces were filled with fluid, epithelial cells, and squamous debris. These were the constituents of amniotic fluid aspirated before birth. The present case suggested that some sudden unexpected deaths in early infancy are delayed deaths caused by amniotic fluid aspiration. PMID- 2589300 TI - Desquamative interstitial pneumonia in an infant. Mimicry of sudden infant death syndrome. AB - A 15-week-old infant girl, without a prior history of overt illness, was found dead while sleeping between her two parents. The gross examination at autopsy showed only congested lungs, and the initial diagnosis was sudden infant death (SID). On microscopic examination, a desquamative interstitial pneumonia (DIP) was observed. The widespread, patchy intraalveolar histiocytic desquamation was associated with lymphocytic infiltration of bronchiolar and aveolar walls, which together provided convincing evidence that an interstitial pneumonitis was the cause of death. A viral etiology seems most likely in view of the accompanying chronic inflammation of bronchial submucosal glands. PMID- 2589301 TI - Murdered to the music of Bob Dylan. AB - The case described is that of a 50-year-old housewife, a State Registered Nurse, who was kicked to death. Death was caused by penetration of the left ventricle by two fractured ribs, a relatively rare form of fatal injury. PMID- 2589302 TI - Response bias in the Honolulu Heart Program. AB - The 14-year incidence rates (1969-1982) for coronary heart disease, cerebrovascular disease (stroke), total mortality, and cause-specific mortality were compared between 8,006 examined and 3,130 nonexamined men of the Honolulu Heart Program using identical surveillance procedures. There was a significant decrease in examination participation with increasing age. Examined men smoked less, weighed more, had a higher level of education, and had a lower percentage of never-married status than did nonexamined men. Total mortality rates, cancer mortality rates, and coronary heart disease incidence rates were higher in nonexamined men, while there were no differences in stroke rates. The average annual response error for total mortality and coronary heart disease rates was underestimated at 8.7% and 5.4%, respectively. The differences in rates were greatest during the first half of the follow-up period and converged during the second half. By the end of 10 years, there were no differences between nonexamined and examined men for any of the endpoints studied. The pattern of convergence of rates suggests a diminishing healthy participant advantage over time. In conclusion, a response bias did occur in this study, but the effect was small and did not alter any of the earlier findings concerning the relative incidence of cardiovascular disease. Because the degree of response bias can vary widely depending on when during follow-up a particular analysis is undertaken, it is recommended that prospective studies monitor, insofar as possible, a sample of nonparticipants in order to ensure valid results. PMID- 2589303 TI - Cardiovascular risk factors and the 25-year incidence of diabetes mellitus in middle-aged men. The Zutphen Study. AB - The association between classical cardiovascular risk factors, including diet, and the 25-year incidence of non-insulin-dependent diabetes mellitus was examined in 841 middle-aged men within the Zutphen Study. The incidence rate was 3.8/1,000 person-years. In univariate analyses, baseline measurements of subscapular and tricipital skinfold thicknesses, body mass index (weight (kg)/height (m)2), cigarette use, resting heart rate, and systolic blood pressure were significantly associated with diabetes incidence. In multivariate survival analyses also taking age, energy intake, and alcohol consumption into account, subscapular skinfold thickness, resting heart rate, and cigarette use were independently related to diabetes incidence. The effect of subscapular skinfold thickness was shown among subjects free of cardiovascular disease at baseline and during follow-up and among cases who developed cardiovascular disease. Cigarette smoking was an independent risk factor only in men who remained free of cardiovascular disease, while the effect of resting heart rate was stronger within incident cases of cardiovascular disease. No associations were found between dietary factors and diabetes incidence. PMID- 2589304 TI - Increase in body fatness as a major determinant of changes in serum total cholesterol and high density lipoprotein cholesterol in young men over a 10-year period. AB - Serum cholesterol rises with age in most Western (and Westernized) populations. To identify causes of this rise, the authors studied 315 young Dutch men in 1976 in the district of Utrecht, The Netherlands, when they were aged 18 or 19 years, and again in various towns in the same region 10 years later, in 1986. These men formed the lower and upper quartiles of the distribution of changes in body mass index (weight (kg)/height (m)2) from 1976 to 1986 in a larger cohort of men representative of all Dutch men aged 18 or 19 years in 1976. In 10 years, mean serum total cholesterol (+/- standard deviation) had increased by 1.20 +/- 0.88 mmol/liter (46 +/- 34 mg/100 ml), and high density lipoprotein (HDL) cholesterol had decreased by 0.12 +/- 0.21 mmol/liter (4.6 +/- 8.1 mg/100 ml). The mean increase in body mass index was 2.7 +/- 2.5 kg/m2, and the mean increase in body fat percentage (assessed from skinfolds) was 3.3 +/- 4.6 g/100 g. The mean subscapular:tricipital skinfold thickness ratio--an indicator of body fat distribution--had not changed. In multiple regression analysis, the change in body mass index was the only significant (p less than 0.001) determinant of changes in serum total cholesterol; an increase of 1 kg/m2 in body mass index was associated with an increase of 0.20 mmol/liter (standard error, 0.02) in serum total cholesterol. Changes in body mass index and in smoking habits both contributed significantly toward explanation of changes in HDL cholesterol and in the HDL cholesterol:total cholesterol ratio. If smoking habits were adjusted for, HDL cholesterol decreased by 0.02 mmol/liter and the HDL cholesterol:total cholesterol ratio decreased by 0.012 (standard error, 0.001) for every 1 kg/m2 increase in body mass index. Changes in body fat distribution, as assessed by skinfold ratio, were not associated with changes in lipids. By interpolation, the authors estimated that for the full cohort of men, including the second and third quartile of body mass index changes, the mean rise in cholesterol had been 1.15 mmol/liter (44 mg/100 ml), of which 0.47 mmol/liter could be explained by the estimated rise in body mass index of 2.4 kg/m2. An increase in body fatness between ages 19 and 29 years is a powerful determinant of the rise in total cholesterol and the fall in HDL cholesterol occurring over that period of time. PMID- 2589305 TI - Dose-response relation between arsenic concentration in well water and mortality from cancers and vascular diseases. AB - Age-adjusted mortality rates were analyzed to examine the dose-response relation between ingested arsenic levels and risk of cancers and vascular diseases among residents in the endemic area of blackfoot disease, a unique peripheral vascular disease associated with long-term exposure to high-arsenic artesian well water and confined to the southwestern coast of Taiwan. The arsenic levels in well water determined in 1964-1966 were available in 42 villages of the study area, while mortality and population data during 1973-1986 were obtained from the local household registration offices and Taiwan Provincial Department of Health. Age adjusted mortality rates from various cancers and vascular diseases by sex were calculated using the 1976 world population as the standard population. A significant dose-response relation was observed between arsenic levels in well water and cancers of the bladder, kidney, skin, and lung in both males and females, and cancers of the prostate and liver in males. However, there was no association for cancers of the nasopharynx, esophagus, stomach, colon, and uterine cervix, and for leukemia. Arsenic levels in well water were also associated with peripheral vascular diseases and cardiovascular diseases in a dose-response pattern, but not with cerebrovascular accidents. The dual effect of arsenic on carcinogenesis and arteriosclerosis and the interrelation between these two pathogenic mechanisms deserve more intensive study. PMID- 2589306 TI - Body size and breast cancer risk assessed in women participating in the Breast Cancer Detection Demonstration Project. AB - In a case-control study that included 2,560 breast cancer cases and 2,679 controls, the authors examined the association between body size and breast cancer with the use of measured height and weight of white US women. The subjects were women aged 26-93 years recruited between 1973 and 1975 for participation in the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. After controlling for the effect of potential confounders, the relative risks of breast cancer across increasing quartiles of height were 1.00, 1.07, 1.15, and 1.27 (p = 0.001, test for trend). The effect of weight independent of height was evaluated using indices of relative weight (e.g., weight/height1.5, weight/height2), and the authors identified excess weight as a risk factor for breast cancer among women who had experienced natural menopause and among women aged 50 years or older at diagnosis. Among women aged 50 years or older, for example, the relative risks of breast cancer for increasing quartiles of weight/height1.5 were 1.00, 1.04, 1.40, and 1.29 (p = 0.0006, test for trend). An inverse association between relative weight and breast cancer risk was suggested for women younger than age 50 years at diagnosis. However, the apparent protective effect of high relative weight was restricted to women with small tumors, suggesting a detection bias. PMID- 2589307 TI - Noncontraceptive estrogen use and epithelial ovarian cancer. AB - The relation of noncontraceptive estrogen use to epithelial ovarian cancer was evaluated in a case-control study conducted in hospitals mainly in the northeastern United States. There were 377 cases diagnosed within the year before hospital admission and 2,030 hospital controls; data were collected by interview in the hospital. Compared with women who never took noncontraceptive estrogens, the overall relative risk estimate for women whose estrogen use lasted at least one year and was not combined with progestogens or testosterone was 1.2 (95% confidence interval (CI) 0.8-1.9), after taking into account risk factors for ovarian cancer. There were 55 cases of the endometrioid, clear cell, or malignant mixed mesodermal cell type; the corresponding relative risk estimate was 0.9 (95% CI 0.3-3.0). There were 26 cases of undifferentiated cell type, with a relative risk estimate of 3.6 (95% CI 1.2-11). Relative risk estimates were similar in a subset of the cases (57%) for which pathology slides were reviewed. For estrogen use of long duration, use of high-dose preparations, or use in the distant past, the relative risk estimates were not significantly different from 1.0. The estimates were elevated for some categories of use, but not consistently--for example, for an interval of 5-9 years since estrogen use began (relative risk (RR) = 2.7), but not after shorter or longer intervals, and for use of conjugated estrogens with a dose of 0.3 mg (RR = 3.2) or 1.25 mg (RR = 2.4), but not for doses of 0.625 mg or 2.5 mg. The relative risk estimate was also elevated for use by nulliparous women (RR = 2.4). The results suggest that, overall, noncontraceptive estrogen use is not associated with the risk of epithelial ovarian cancer. Furthermore, our data do not support the hypothesis that estrogens increase the risk of endometrioid ovarian cancer. The elevated estimates could be due to multiple stratification of the data, but they should be explored in further studies, given the lethality of ovarian cancer and the common use of estrogens by postmenopausal women. PMID- 2589308 TI - Chronic lymphocytic leukemia in relation to chemical exposures. AB - As part of a population-based case-control study carried out in four areas of the United States, 427 cases of chronic lymphocytic leukemia diagnosed between July 1, 1977, and December 31, 1981, and 1,683 controls were interviewed regarding their history of chemical exposure. Respondents were asked if they had ever been "highly exposed" at home, at work, or elsewhere to one or more of a list of chemicals or to any other such substances not on the list. These chemicals were categorized into 20 exposure groups based on chemical composition. Odds ratios were calculated adjusting for age, sex, race, education level, and geographic location by means of unconditional logistic regression. Increased risks were associated with reported past exposure to acid-containing chemicals, "other caustic substances," aliphatic hydrocarbons, and chlorinated hydrocarbons. Because of the large number of exposures investigated in this study, and because of the relatively imprecise means the authors had to assess exposure, further research is needed to verify these findings. PMID- 2589309 TI - Smoking, alcohol, occupation, and hair dye use in cancer of the lower urinary tract. AB - This case-control study was based on 137 Caucasian and 124 Japanese cases of urinary tract cancer identified in Hawaii between 1977 and 1986. Each case was matched on sex, age, and race to two population-based controls. Heavy cigarette smokers (41 or more pack-years for men; 21 or more pack-years for women) had a significantly elevated risk compared with nonsmokers (odds ratio (OR) = 6.2, 95% confidence interval (CI) 3.4-11.1 for the men; OR = 2.8, 95% CI 1.2-6.3 for the women). When the men and women were combined, employment in high-risk industries (includes machinery, automotive, and textiles, among others) was significantly associated with cancer risk (OR = 1.6, 95% CI 1.1-2.3). Alcohol intake and hair dye use showed weaker positive associations with risk that were not statistically significant. PMID- 2589310 TI - Adenocarcinoma and wood. AB - The relation of adenocarcinoma of the facial sinuses and exposure to wood dust has been recognized for 20 years. As the tracheobronchial mucosa is similar to that lining the sinuses, a link between bronchial adenocarcinoma and wood dust exposure has been postulated. To test this hypothesis, a case-control study was conducted, based on all the histologically proven cases of adenocarcinoma of the lung reported to the tumor registry of the Doubs region of France from 1978 to 1985 and random population controls matched for age and residence. A questionnaire on occupational exposure and tobacco consumption was completed by 53 cases and 160 controls. Exposure to wood was similar for both groups, the crude relative risk (odds ratio) being 1.06; adjustment for tobacco consumption did not modify this value. Exposure to wood dust does not seem to be an occupational risk factor in the genesis of bronchial adenocarcinoma. PMID- 2589311 TI - Risk of enamel fluorosis associated with fluoride supplementation, infant formula, and fluoride dentifrice use. AB - Eight hundred fifty 11- to 14-year-old residents of nonfluoridated communities in Massachusetts and Connecticut, who were born between 1972 and 1975, were investigated in a case-control study of the possible association between enamel fluorosis and exposure to fluoride supplements, infant formula, and/or fluoride dentifrice. The effect of median household income, an indicator of socioeconomic status, was also examined. Clinical examination, using the Fluorosis Risk Index, a fluorosis index developed for this project, allowed cases and controls to be identified based upon the specific time period of exposure to the various sources of ingested fluoride. Risk factor exposure was assessed via a mailed questionnaire with a response rate of 80%. Mild-to-moderate enamel fluorosis was strongly associated with fluoride supplementation during the first six years of life (odds ratio = 4.0) and with median household income (odds ratio = 6.6). Subjects in the middle median household income group who had used fluoride supplements through the first six years of life had a 28-fold increase in the risk of fluorosis compared with unexposed subjects in the lower median household income group. An odds ratio of 1.7 associated with infant formula use was suggestive of an increased risk of enamel fluorosis as was an odds ratio of 2.9 associated with fluoride dentifrice use. PMID- 2589312 TI - Epidemiologic study of deaths and injuries due to tornadoes. AB - A case-control study, using both matched and unmatched controls, was carried out on individuals who were injured or killed by a series of tornadoes that passed through Ontario, Canada, on May 31, 1985. Many serious injuries (25%) and almost all (83%) deaths were the result of becoming airborne, while most minor injuries (94%) were due to being struck by objects. Head injury was the most common injury type. Few (21%) of those in buildings chose the recommended location, and most (61%) were not in the least damaged part. Most (91%) had less than one minute's warning, and only 47% had a functioning radio at the time the tornado hit. The following risk factors for injury and death were identified: poor building anchorage; location other than in a basement, especially outdoors; age over 70 years; and high wind strength. These findings support previous findings and point to measures which have potential for preventing death or serious injury in future tornadoes: adequate warning systems and public education to ensure that individuals understand the warning and respond by seeking appropriate shelter. Those in adequately anchored buildings should shelter in an interior room or basement. Those who are outdoors, in poorly anchored buildings, mobile homes, or portable classrooms require access to an adequately anchored building, preferably with a basement, during severe storm warnings. This should be arranged by local authorities. PMID- 2589314 TI - Costs and statistical power associated with five methods of collecting occupation exposure information for population-based case-control studies. AB - The ascertainment of information on past occupational exposure of study subjects is perhaps the main problem in case-control studies of occupational risk factors. Several methods have been proposed and used but little is known of their relative merits. The present study, undertaken in the context of a large ongoing case control study of occupational cancer in Montreal, was designed to compare the costs of and statistical power to be derived from five plausible methods of data collection: 1) job titles abstracted from routine records, 2) job titles abstracted from routine records and processed through a job exposure matrix to derive exposure data, 3) job titles obtained by interview, 4) job titles obtained by interview and processed through a job exposure matrix to derive exposure data, and 5) job descriptions obtained by interview and processed by a team of experts to derive exposure data. Statistical power of the five methods was derived for 160 hypothetical risk factors, partly on the basis of empirical data from the data set and partly on the basis of some theoretical constructs. The design based on interview and expert evaluation was used as a reference, and the degree of misclassification of other methods was estimated in relation to this reference. For fixed sample size the interview and expert evaluation design was estimated to be much more costly than the others, but it provides much greater statistical power for detecting risks. Under the conditions of this investigation, this design was the most cost-effective. However, it is not clear to what extent this finding is generalizable. PMID- 2589313 TI - The importance of age in evaluating anthropometric indices for predicting mortality. AB - Weights and heights were obtained on approximately 4,000 preschool-aged children in six rural villages of West Java between 1977 and 1978. Deaths occurring in the ensuing 18 months were ascertained at three-month intervals. The abilities of relative weight for height and height for age to discriminate children at greatest risk of dying were compared. Younger children (less than or equal to two years) with low height for age (less than 95% of the reference median) were at greater risk of dying than children of the same age who were not stunted. This risk declined with increasing age, and among children aged 3-5 years, those who were stunted were at no greater risk than those of normal height for age. The mortality risk associated with mild wasting (80-90% of the reference median) also declined with increasing age. However, the risk of dying among moderately to severely wasted (less than 80% of the reference median) children increased with increasing age. These results suggest that stunting, rather than wasting, puts younger children at greater risk of death, but among older children, wasting carries a greater relative mortality risk over an 18-month period. PMID- 2589315 TI - Log-linear models for the analysis of matched cohort studies. AB - The application of conditional logistic regression to the analysis of matched case-control studies has now become quite customary. In addition, it is well known that software designed to fit linear logistic and log-linear models can be used in these analyses. The application of conditional logistic regression to cohort designs is described, and an approach is developed that adapts the linear logistic and log-linear models for the analysis of prospectively collected data. Specific situations discussed include matched pairs, 2:1 matching, and studies in which some subjects are pair matched and others matched 2:1. The methods are illustrated with numeric examples. PMID- 2589316 TI - Re: "Breast cancer before age 45 and oral contraceptive use: new findings". PMID- 2589317 TI - Re: "Epidemiology: questions of science, ethics, morality, and law". PMID- 2589318 TI - The natural history of cytogenetically abnormal fetuses detected at midtrimester amniocentesis which are not terminated electively: new data and estimates of the excess and relative risk of late fetal death associated with 47,+21 and some other abnormal karyotypes. AB - We report the results of an ongoing survey of rates of spontaneous death of fetuses with chromosome abnormalities detected at second-trimester amniocentesis in which the mother did not elect abortion. Estimated excess risks (and conservative 90% confidence intervals) of spontaneous fetal death for various cytogenetic abnormalities are as follows: 47,+21, 25.6% (18.0%-34.0%); 47,+18, 63.8% (49.3%-79.8%); 47,+13, 36.5% (11%-69.7%); 45,X, 65.3% (41.0%-84.2%); and mosaic 45,X/46,XX, 10.8% (1.0%-26.8%). There is little evidence for an excess risk of fetal death, at least following amniocentesis, for 47,XXX, 47,XXY, or 47,XYY. The excess risks of fetal death were adjusted for the likelihood that a fetus of normal karyotype would undergo spontaneous fetal death in a population of older maternal age similar to that in which prenatal cytogenetic diagnosis is undertaken. The absolute fetal death rates when this factor is ignored are about 3.5% higher (i.e., may be derived by adding 3.5% to the values given). The excess risks are those which are most appropriate for use in estimating the contribution of chromosome abnormalities to spontaneous fetal death. PMID- 2589319 TI - A contiguous, 3-Mb physical map of Xq28 extending from the colorblindness locus to DXS15. AB - Using pulsed-field gel electrophoresis (PFGE), we have generated a 3-megabase (Mb) physical map of Xq28, a region of the human genome known to contain many disease loci. We have determined the location of the genes for protan/deutan colorblindness (R/GCP), factor VIII (F8), glucose-6-phosphate dehydrogenase (G6PD), and a series of RFLPs and have derived the following order for this region: R/GCP-GdX-G6PD-F8-DXS115-DXS33-DXS134-D XS15. Using newly isolated probes, we have also established the direction of transcription of F8 within the map and have localized CpG islands flanking this gene. PMID- 2589320 TI - Recessive inheritance of a relative fat pattern. AB - We defined a relative-fat-pattern index (RFPI) as the ratio of subscapular skinfold thickness to the sum of subscapular and suprailiac skinfold thicknesses and computed RFPI for 774 adults (age greater than or equal to 25 years) in 59 pedigrees ascertained through cases of cardiovascular disease. Likelihood analysis of RFPI supported recessive inheritance of an allele with a frequency of 46%, which elevated mean RFPI from .412 to .533 when homozygous. The analysis apportioned the variance in RFPI as 42.3% due to the major locus, 9.5% due to polygenic inheritance, and 48.2% due to random environmental effects. Homozygotes for the recessive allele tended to have small suprailiac skinfold thicknesses rather than large subscapular skinfold thicknesses. Homozygotes were more frequent in younger than in older cases of obesity, coronary heart disease, essential hypertension, and diabetes mellitus; the increase was significant for all but diabetes. PMID- 2589321 TI - Physical localization of two DNA markers closely linked to the cystic fibrosis locus by pulsed-field gel electrophoresis. AB - Our previous linkage analysis suggested that the DNA segment D7S122 is located between MET and D7S8, the two genetic markers that are thought to flank the cystic fibrosis locus (CF). Subsequent chromosome walking experiments revealed that D7S122 in within close distance to another randomly isolated DNA marker, D7S340. To determine the physical relationship among D7S122, D7S340, MET, and D7S8, we have constructed a long-range restriction map of the region containing these four DNA segments, by using DNA from a human/hamster somatic hybrid cell line 4AF-KO15 (containing a single human chromosome 7) and a series of rare cutting restriction enzymes. The combined results of complete, partial, and double digestion analyses confirm that D7S122 and D7S340 are located between MET and D7S8. The order of these markers is MET-D7S340-D7S122-D7S8, with distance intervals of approximately 500, 10, and 980 kbp, respectively. Together with family analysis, this information will be useful for eventual identification of the CF gene. PMID- 2589322 TI - Localization of the mutation in an extended family with Charcot-Marie-Tooth neuropathy (HMSN I). AB - Hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth (CMT) disease is an autosomal dominant peripheral neuropathy. In some CMT families linkage has been reported with either the Duffy blood group or the APOA2 gene, both located on chromosome 1q. More recently, linkage has been found in six CMT families with two chromosome 17p markers. We extensively analyzed a multi generation Charcot-Marie-Tooth family by using molecular genetic techniques in order to localize the CMT gene defect. First, we constructed a continuous linkage group of 11 chromosome 1 markers and definitely excluded chromosome 1 as the site of mutation. Second, we analyzed the family for linkage with chromosome 17. The two-point lod scores obtained with D17S58 and D17S71 proved that this Charcot Marie-Tooth family is linked to chromosome 17. Moreover, multipoint linkage results indicated that the mutation is most likely located on the chromosome 17p arm, distal of D17S71. PMID- 2589323 TI - Simulation of pedigree genotypes by random walks. AB - A random walk method, based on the Metropolis algorithm, is developed for simulating the distribution of trait and linkage marker genotypes in pedigrees where trait phenotypes are already known. The method complements techniques suggested by Ploughman and Boehnke and by Ott that are based on sequential sampling of genotypes within a pedigree. These methods are useful for estimating the power of linkage analysis before complete study of a pedigree is undertaken. We apply the random walk technique to a partially penetrant disease, schizophrenia, and to a recessive disease, ataxia-telangiectasia. In the first case we show that accessory phenotypes with higher penetrance than that of schizophrenia itself may be crucial for effective linkage analysis, and in the second case we show that impressionistic selection of informative pedigrees may be misleading. PMID- 2589324 TI - Beta-thalassemia mutations in Indonesia and their linkage to beta haplotypes. AB - A total of 72 chromosomes from 36 Indonesian patients, 23 with beta-thalassemia major and 13 with Hb E-beta-thalassemia, were analyzed by specific oligonucleotide hybridization after DNA amplification. Thirteen had the beta E mutation (codon 26 GAG----AAG). Of the 59-beta-thalassemic chromosomes, 32 were of the variant IVS-1 nt5 (G----C). Seven had the mutation IVS-2 nt654 (C----T), one had the mutation codon 41/42 (deletion CTTT), and one had the mutation codon 17 (AAG----TAG). Another six with the mutation IVS-1 nt1 (G----T), one with the mutation IVS-1 nt1 (G----A), four with the mutation codon 15 (TGG----TAG), one with a mutation codon 30 (AGG----ACG), and one with a mutation codon 35 (deletion C) were first identified by direct sequencing of a patient's genomic DNA followed by further hybridizing other patients' DNA with the appropriate oligonucleotide probes. Five did not carry the common mutations previously described in Asian populations. The four most prevalent mutations encountered made up 83% of the total number of beta-thalassemic chromosomes studied. The most common mutation, IVS-1 nt5 (G----C), was mostly associated with two different haplotypes. PMID- 2589325 TI - Brain-stem auditory evoked potentials in the fragile X syndrome. PMID- 2589326 TI - Relationship of mortality, occupation, and pulmonary diffusing capacity to pleural thickening in the First National Health and Nutrition Examination Survey. AB - We studied the relationship of pleural thickening consistent with asbestos exposure to mortality, career employment in asbestos-related jobs, and pulmonary diffusing capacity among participants in the first National Health and Nutrition Examination Survey. Three "B" readers examined chest X-rays to identify 59 individuals with such pleural abnormalities. From 1975 to 1984, the all-cause mortality rate ratio (RR) comparing males with and without occupational pleural thickening was 1.3 (95% C.I. 0.8-2.2). For lung cancer, the mortality RR for males was 3.0 (95% C.I. 1.0-9.1). Career asbestos work was not associated with occupational pleural thickening among men, probably because some with the condition had only short-term exposure to asbestos. Pulmonary diffusing capacity was lower in those with occupational pleural thickening, taking smoking into account. These results suggest that individuals in the general population who have occupational pleural thickening are at risk for some of the health consequences of asbestos work, including lung cancer, even if they were not career asbestos workers. PMID- 2589327 TI - Occupation and squamous cell cancers of the pharynx and sinonasal cavity. AB - Lifetime job histories from a population-based case-control study of squamous cell carcinomas of the oro- and hypopharynx (OHPC), nasopharynx (NPC), and sinonasal cavity (SNC) were systematically examined to generate new hypotheses as well as to test previously noted associations between occupation and the cancers under study. The effects of both duration of employment in a particular job and the timing of the employment in relation to cancer diagnosis were investigated in a stratified analysis that controlled for cigarette smoking, alcohol intake, and other major risk factors. Overall, data on 231 cases and 552 controls were analyzed. Occupations at increased risk of OHPC included "food service" workers in the "retail trade" industry (odds ratio = 1.9; 95% confidence interval = 1.0 3.6), "vehicle mechanics" in the "repair services" industry (OR = 2.5; CI = 0.8 8.3), "industrial mechanics" (OR = 31.0; CI = 3.0-315.1), and "carpenters" in the "construction" industry (OR = 1.5; CI = 0.7-3.4). For NPC, similar patterns of increased risk were found for "food service" workers and "vehicle mechanics." For "carpenters" in the "construction" industry, the relative risk estimate was almost five (OR = 4.8; CI = 1.2-19.4). Increases in SNC risk were noted for "food service" workers, as well as a number of occupations in the "lumber and wood product manufacturing" industry, including "forestry and logging" (OR = 2.0; CI = 0.5-8.2), and "wood working machine operators" (OR = 7.9; CI = 1.6-39.2). In each of these instances, the relative risk estimates increased with increasing duration in the job and when a 15-year induction/latency period was taken into account. PMID- 2589329 TI - Study of respiratory impairment among pesticide sprayers in Mango plantations. AB - Pulmonary function studies were conducted on 489 pesticide workers engaged in spraying operations on mango plantations. These workers were exposed to a variety of organochlorine and organophosphorus pesticides. A reference group consisting of 208 controls, belonging to the same socioeconomic stratum, was taken from the same area for purposes of comparison. The results of the study showed 36.5 and 41.5% prevalence of respiratory impairment in the exposed workers and in the controls, respectively. The most common pulmonary impairment among the exposed subjects (18.8%) and controls (16.9%) was of the restrictive type, followed by mixed ventilatory defect. Bronchial obstruction affected 2.5 and 3.7% of the exposed and control populations, respectively. In a comparison of the prevalence of total respiratory impairment in the pesticide workers and the controls, the nonsmokers did not show any significant difference in this study. The prevalence rate of respiratory impairment showed an increasing trend in different exposure groups (p less than 0.05), thereby clearly indicating a dose effect. The study revealed that occupational exposure to pesticides had a direct bearing on the respiratory impairment identified in the exposed workers. PMID- 2589330 TI - Outcome of pregnancy in women engaged in laboratory work at a petrochemical plant. AB - The aim of the investigation was to study whether laboratory work or other types of chemical work at one petrochemical plant were associated with an increased risk for miscarriage or reduced birthweight. The study was based on questionnaire data for 95% of the women working at the plant between 1973 and 1987. A statistically significant difference between observed and expected number of miscarriages (p less than 0.05) was seen during the period 1970-1974 among women working in one of the laboratories during the first trimester. No suspicions could be raised against any specific chemical as a cause of the unsuccessful pregnancies. The results do not indicate the presence of an increased risk today. PMID- 2589328 TI - Relation of radon exposure and tobacco use to lung cancer among tin miners in Yunnan Province, China. AB - We studied the relation of radon exposure and tobacco use to lung cancer among tin miners in Yunnan Province in the People's Republic of China. Interviews were conducted in 1985 with 107 living tin miners with lung cancer and an equal number of age-matched controls from among tin miners without lung cancer to obtain information on lung cancer risk factors including a detailed history of employment and tobacco use. Occupational history was combined with extensive industrial hygiene data to estimate cumulative working level months (WLM) of radon daughter exposure. Similar data were also used to estimate arsenic exposure for control in the analysis. Results indicate an increased risk of lung cancer for water pipe smoking, a traditional form of tobacco use practiced in 91% of cases and 85% of controls. Ever use of water pipes was associated with a twofold elevation in risk when compared with tobacco abstainers, and a dose-response relation was observed with increasing categories of pipe-year (dose times duration) usage. Estimated WLM of radon exposure varied from 0 to 1,761 among subjects but averaged 515 in cases versus only 244 in controls. Analyses indicated that the persons in the highest quarter of the radon exposure distribution had an odds ratio (OR) = 9.5 (95% confidence interval = 2.7-33.1) compared to persons without radon exposure after controlling for arsenic exposure and other potential confounders. Examination of duration and rate of radon exposure indicated higher risk associated with long duration as opposed to high rate of exposure. Cross-categorizations of radon exposure and tobacco use suggest greater risk associated with radon exposure than tobacco in these workers. PMID- 2589331 TI - Parallel track for investigational AIDS drugs. PMID- 2589332 TI - Central American countries need drug products and medical supplies. PMID- 2589333 TI - In vitro inactivation of gentamicin by ampicillin. PMID- 2589334 TI - Ambiguous dosing information in Guide to Antimicrobial Therapy. PMID- 2589335 TI - Pain associated with an ambulatory-care infusion device. PMID- 2589336 TI - Clinical pharmacy as a career. PMID- 2589337 TI - Transition. PMID- 2589338 TI - Clinical career ladders: application to hospital pharmacy practice. AB - The reasons for job dissatisfaction among hospital pharmacists are reviewed, and an option for ameliorating the problem by offering clinical career ladders is advanced. Not enough new pharmacists are being trained to replace those leaving the profession, and hospital pharmacy managers seeking to recruit and retain quality pharmacists are facing stiff competition from retail outlets, academia, and the pharmaceutical industry. Hospital staff pharmacists report less of a sense of accomplishment than other workers and are more likely to change jobs. Although inadequate pay and benefits are frequently cited, one investigator found that the greatest source of dissatisfaction was the lack of opportunity for advancement. Other professions facing similar problems have experimented with a system of parallel career ladders in which alternatives to the traditional managerial advancement track are offered. Staff nurses on a clinical ladder remain in a direct patient-care role while ascending a hierarchy of clinical practice levels; each level brings greater responsibility and rewards. Outcomes have included improved recruitment, decreased turnover, and increased interest in educational programs. In pharmacy, each level of a clinical career ladder would be defined by explicit criteria for knowledge and skill in patient care and drug therapy. As in nursing, such a ladder would create advancement opportunities and reward the acquisition of knowledge and skills. Several hospital pharmacy departments now offer clinical career ladders. Implementation of clinical career ladders has the potential to enhance the job satisfaction of hospital pharmacists and improve their recruitment and retention. PMID- 2589339 TI - Clinical career ladders: Thomas Jefferson University Hospital. AB - The clinical career ladder program developed for pharmacists at Thomas Jefferson University Hospital, a 700-bed teaching hospital, is described. A task force was assembled to develop a clinical career ladder that would parallel the managerial advancement track in terms of rewards and recognition. The task force created separate lists of competencies for staff and clinical pharmacists and ranked the competencies according to their complexity and the number of years most pharmacists would need to achieve them. Separate pathways were established for staff and clinical pharmacists: staff pharmacist I, II, and III and clinical pharmacist I, II, and III. A salary scale designed to provide meaningful salary increases between levels was established. Nearly all pharmacists who are hired begin at level I and are allowed to apply for promotion to level II within six months. Opportunities for promotion occur twice annually. Pharmacists who have received an overall rating of effective or outstanding at the most recent performance appraisal may submit documented evidence that they have gained the knowledge and skills required at the higher level. A promotions review board evaluates each application and informs the director of pharmacy as to whether the applicant meets the criteria for promotion. Response to the program has been favorable, as indicated by the number of pharmacists who have applied for promotion and the quality of their applications. A carefully planned clinical career ladder program was well received by pharmacists, who responded by acquiring the knowledge and skills necessary for promotion. PMID- 2589340 TI - Clinical career ladders: Hamot Medical Center. AB - The clinical career ladder program for pharmacists at Hamot Medical Center (HMC), a 500-bed not-for-profit community teaching hospital, is described. Between 1980 and 1989 a career ladder at HMC evolved from an idea to an established program with parallel administrative, business, and clinical tracks. The development of the career ladder mirrored the growth of clinical programs and the diversification of pharmaceutical services. A formal plan for a clinical ladder was developed when the first satellite pharmacy opened in 1984. An entry-level pharmacist at HMC starts with a six-month period during which he or she learns the drug distribution system and prepares for several certification tests. The employee is then promoted to staff pharmacist. Staff pharmacists are promoted to clinical pharmacist II (CP II) upon meeting requirements for competence in a broad range of clinical skills and knowledge. Candidates for the position of clinical pharmacist specialist (CP I) must have either a minimum of three years of experience as a CP II or a Pharm.D. degree and have established an area of clinical expertise. A CP I can progress to assistant and associate director positions as vacancies occur. The clinical ladder has enhanced job satisfaction and encouraged the development of clinical practitioners who provide improved care. Problems have included time constraints, competition for positions, and management of incentives. A parallel career ladder program with a clinical track has enhanced the growth of pharmacy practice at HMC and improved the quality of pharmaceutical care. PMID- 2589342 TI - Clinical career ladders: the Washington Hospital Center. AB - The clinical career ladder program developed for pharmacists at The Washington Hospital Center, an 852-bed not-for-profit teaching institution, is described. Many new pharmacists hired during a period of rapid departmental expansion from 1979 to 1984 lacked the knowledge and skills needed to practice effectively in an increasingly complex clinical environment. The existence of a single class of staff pharmacists led to inequities in salaries. A continuing-education program was instituted, but some mechanism of motivating the pharmacists and correcting problems in recruitment, retention, and productivity was needed. In 1984 the department implemented a clinical career ladder with four levels: staff pharmacist, clinical pharmacist, senior clinical pharmacist, and clinical services manager. Duties and responsibilities range from drug distribution, technical supervision, and provision of basic drug information at the staff pharmacist level to supervision of pharmacy services in specified patient-care areas, administrative supervision, and program planning and development at the clinical services manager level. Equity adjustments were made when the program was implemented. Employees who meet the minimum requirements and have received above-standard performance evaluations are considered for promotion. To be promoted to clinical services manager, an employee must apply formally. The program has reduced turnover, particularly among the most highly skilled and productive employees, and has attracted new employees. A career ladder eased problems in employee retention and recruitment, eliminated wage inequities, and became an important motivational force for the professional staff. PMID- 2589341 TI - Clinical career ladders: the Moses H. Cone Memorial Hospital. AB - A competence- and achievement-based advancement program developed for pharmacists at The Moses H. Cone Memorial Hospital, a 530-bed community teaching hospital, is described. In 1985 pharmacy management recognized the need to provide an incentive program to reward achievements by staff clinical pharmacists, recognize their increased responsibilities, and increase the department's ability to retain qualified practitioners. Adding another rung to the existing administrative career ladder was not desirable, so a new job category, pharmacist II, was created. Employees are evaluated for promotion to pharmacist II on the basis of tenure, performance, and elective professional and service activities. A point system is used to objectively score achievements; to be promoted, an employee must accumulate 50 points during a two-year period. The number of staff pharmacists who can advance is limited not arbitrarily but rather by the application of challenging criteria. Employees are responsible for submitting documentation of their achievements to a review committee, which meets quarterly to evaluate applications and award points. Of 13 applicants since 1985, 10 have been promoted. Because of problems in evaluating the performance of pharmacist II employees, providing them time to conduct research, and incorporating specialty practice areas into the program, plans are being made to institute a more structured career ladder system with separate managerial, clinical, and educational tracks. A competence- and achievement-based advancement program with a single step was an improvement over the former system but lacked the balance and comprehensiveness offered by more structured career ladder programs. PMID- 2589343 TI - Clinical career ladders: St. Vincent Hospital and Health Care Center. AB - The career ladder program developed for pharmacists at St. Vincent Hospital and Health Care Center (SVH), a 625-bed community hospital, is described. Before 1986 the only advancement program for pharmacists at SVH was a traditional managerial one. The need for a system that would reward outstanding pharmacists both professionally and financially and prevent increases in turnover led to the development of a three-tiered ladder system in which clinical expertise and participation in elective professional activities are important keys to advancement. All baccalaureate-level pharmacists are hired at level I. Level II represents the standard of pharmacy practice at SVH. Pharmacists promoted to level III have made a major contribution. Advancement is contingent upon the accumulation of points awarded for performance evaluations, elective activities, and tenure. In addition to distributive and clinical duties, level II and III pharmacists must participate in special projects or on committees. Promoted pharmacists must accumulate additional points annually to remain at the higher level. The program was objected to by some staff members who believed that it would cut into personal time and give certain pharmacists preferred work schedules. Nevertheless, several promotions have quickened interest in the program, and participation in advancement-related activities has increased. The career ladder program has stimulated employees' professional and financial growth, enhanced the quality and quantity of pharmaceutical services, and averted potential increases in staff turnover. PMID- 2589344 TI - Clinical career ladders: Jewish Hospital of St. Louis. AB - The clinical career ladder program developed for pharmacists at Jewish Hospital, a 500-bed tertiary-care teaching institution, is described. In 1983 the hospital's salary structure was re-evaluated. The pharmacy department seized this opportunity to create a clinical career ladder program that would accommodate the changing nature of the profession. Management informally interviewed staff members and developed their opinions into a proposal, which was accepted by the job evaluation committee. The career ladder has three levels. Level I pharmacists carry out basic practice duties. Level II pharmacists have additional responsibilities, notably maintaining a procedure manual, training, and performing an advanced clinical function. At level III, pharmacists develop, implement, and manage a clinical program. Pharmacists are promoted for having achieved a certain level of practice. They are not given new duties upon promotion; rather, they have already taken them on. Advancement can occur at any speed, and it is possible to voluntarily step back to a previous level. The novelty of the program, design flaws, and a series of modifications have created some frustration and confusion among the staff, but the career ladder is otherwise a success. Recruitment has improved, the department's organizational chart is aligned more horizontally, and the pharmacists are being trained for nondistributive roles. In retrospect, management would not have based the program on staff interviews but would have established a formal committee. The effort needed to establish and adjust to a clinical career ladder is great but so is the potential payoff. PMID- 2589345 TI - Robotic system for i.v. antineoplastic drug preparation: description and preliminary evaluation under simulated conditions. AB - A robotic system for preparing doses of i.v. antineoplastic drugs is described, and measurements made with the system are compared for accuracy and reproducibility with those made by pharmacists and technicians. System hardware consists of a robotic arm, a 16-bit microcomputer, a bar-code reader, a voice synthesizer, and an electronic balance. The software includes a menu-driven main program, executable files for each robotic activity, and an interface to allow control to pass between the program and the files. The program has routines for matching the software to the hardware; for entering information about the patient, the name of the drug ordered, and the dose; for checking the dose; for selecting the number and size of the vials to be used; for specifying the manipulations of the robotic arm; for printing labels; and for maintaining records. The robot fills an order by getting and placing a vial, inserting a needle into it and withdrawing the drug, weighing the vial, agitating the container to dissolve its contents, reading a bar code, placing a syringe in a syringe manipulator, and getting an i.v. container and injecting the drug into it. Detection of any errors by a series of self-checks arrests execution of an order. No significant differences in accuracy and precision were found between the robotic system and humans performing the same tasks under simulated conditions. The robotic system required less time than humans and eliminated the possibility of direct human contact with the i.v. admixture. Under simulated conditions, a robotic system developed to assist in the preparation of i.v. antineoplastic drugs was as accurate as a manual system and was more time efficient. PMID- 2589347 TI - System for voluntary reporting of adverse drug reactions in a university hospital. AB - The development and implementation of a system to improve voluntary reporting of adverse drug reactions (ADRs) is described. A preliminary study comparing three concurrent voluntary reporting systems at a 327-bed university teaching hospital demonstrated the ability of medical records personnel to identify ADRs that were documented in the medical record but not reported under the voluntary system. It was concluded that a concurrent voluntary reporting system would be coupled with a medical record review process that would focus reporting on clinically important and unexpected ADRs. Failures to report ADRs would be handled through existing procedures of staff privilege allocation and peer review. The baseline ADR rate was determined. A telephone reporting system was established for the medical staff. After review of reported reactions by pharmacy, feedback was provided to ADR reporters and the medical staff. During the first three months under the new system, 9 of 114 documented ADRs were reported, compared with none in the three months before the program began. All ADRs defined as reportable were reported. An ADR-reporting system designed to encourage voluntary reporting of selected reactions, monitor the baseline rate of ADR occurrence, and assess compliance with reporting criteria appears to operate satisfactorily. PMID- 2589346 TI - Factors influencing pharmacists' selection of their first practice setting. AB - Factors that influenced the choice of initial practice setting among pharmacists who had completed the majority of their experiential training in a hospital setting were determined. A questionnaire was mailed to all eligible pharmacists who successfully completed the Ohio pharmacist licensure examination in June or September 1987. Respondents were asked to (1) provide demographic data, (2) rate the importance of 23 factors that a pharmacist might consider when choosing a practice site, and (3) rate the desirability of a pharmacist position in their major hospital internship site, as well as positions they had considered in other hospitals and in community pharmacies. The predictive accuracy of four decision making models--the weighted compensatory choice model, the unweighted compensatory choice model, the lexicographic model, and the conjunctive model- also was determined. Of 105 pharmacists surveyed, 53 returned usable questionnaires. Twenty-five had chosen to practice in hospital settings, and 28 had chosen community settings. The factor "is personally rewarding" was mentioned most often by hospital and community pharmacists as the factor that was most important when choosing their first position. The lexicographic model, which postulates that a pharmacist will choose the practice site with the highest performance rating for the most important factor, was the most accurate predictor of respondents' initial practice sites. Pharmacists' perception of how practice sites would rate in terms of the single job-related factor most important to them was the best predictor of whether they chose hospital or community practice initially and whether they chose to work in the hospital in which they served their internship, another hospital, or a community pharmacy. PMID- 2589348 TI - Accuracy and time requirements of a bar-code inventory system for controlled substances. AB - The effect of a bar-code system on personnel time requirements and data-entry accuracy in an existing automated controlled substances inventory system was determined. In the previous system, technicians used a keyboard and alphanumeric codes to enter into the computer data about the physical transfer of controlled substances among hospital areas. A system for barcode data entry was adapted for use with the existing procedure. After learning to use the bar-code system, four experienced technicians entered data by the keyboard method for eight days and the bar-code method for eight days during a 32-day study period. The amount of time required to enter all transactions and the accuracy of data entry were measured. Mean data-entry times for the keyboard and bar-code methods were not significantly different, most likely because of the greater number of manipulations needed for bar-code data entry. The mean percentage error associated with the bar-code method (0.79%) was significantly less than the error associated with the keyboard method (1.53%). For this particular computer system in which bar-code data entry was adapted to existing procedures, use of bar codes to enter controlled substances inventory data was not substantially faster but was more accurate than a traditional key-board data-entry method. PMID- 2589349 TI - National survey of critical-care pharmaceutical services. AB - The results of a national survey of critical-care pharmaceutical services are reported. A questionnaire was mailed on March 8, 1988, to 1500 of the 6800 U.S. hospitals with more than 100 beds. The questionnaire was divided into four sections: (1) critical-care pharmaceutical services; (2) critical-care clinical pharmacy activity; (3) critical-care pharmacy standards; and (4) general information on the hospital, including pharmaceutical services provided to patients who are not critically ill. A total of 613 usable questionnaires were returned, for a response rate of 41%. Respondents from 124 hospitals reported having a critical-care satellite pharmacy. Critical-care beds served by satellite pharmacies were more likely to have unit dose drug distribution services than were critical-care beds not served by satellite pharmacies. The level of clinical and educational services provided to critical-care patients was significantly lower for intensive-care unit (ICU) pharmacists practicing in satellite pharmacies than it was for ICU pharmacists not associated with satellite pharmacies. There were no differences between satellite and nonsatellite ICU pharmacists in either the percentage of a typical day spent providing clinical services to critical-care patients or the percentage of critical-care patients receiving those services. Respondents expected their hospitals to add 301 full time-equivalent critical-care pharmacists to their staffs during the next two years, for a 39% increase. Respondents strongly favored establishing 24-hour unit dose drug distribution and i.v. admixture services, providing inservice education to nurses and physicians, and providing written pharmacokinetic consultations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589351 TI - Effect of primary fluids and dilutional volumes on the delivery of cefazolin sodium by a membrane infusion device. AB - The influence of primary fluids and dilutional volumes on the accuracy of in vitro delivery of cefazolin sodium by gravity flow through a new controlled release membrane infusion device was studied. For primary fluid studies, cefazolin 1 g (as the sodium salt) in 10 mL of sterile water for injection was injected into the drug chamber, which is separated by a membrane from the fluid chamber; the entire dose passes into the fluid chamber over a set time. The inlet port of the fluid chamber was connected to the 1-L primary fluid bag, and the outlet port was connected to an administration set. The primary fluids included 0.9% sodium chloride injection; 5% dextrose injection; 10% dextrose injection; 5% dextrose and 0.45% sodium chloride injection; 5% dextrose, 0.45% sodium chloride, and potassium chloride 20 meq/L injection; and 2.2% amino acids with electrolytes in 25% dextrose injection. For dilutional volume studies, cefazolin sodium 1 g diluted in 5, 10, and 15 mL of sterile water for injection was infused with 0.9% sodium chloride injection. The flow rate was set at 1 mL/min. Serial samples were collected in triplicate every five minutes over a 90-minute period and analyzed by high-performance liquid chromatography. The time needed to deliver more than 95% of the cefazolin doses ranged from 35 to 50 minutes using various primary fluids and from 35 to 55 minutes using various dilutional volumes. The manufacturer recommends that a cefazolin dose be delivered completely within 30 60 minutes. The solutes in the primary fluids and the volume injected did not appear to affect the delivery of cefazolin by a controlled-release membrane device. PMID- 2589350 TI - Evaluation of five procedures for measuring nonstandard doses of nifedipine liquid. AB - Five methods for removing the maximum volume of liquid from a nifedipine capsule were evaluated for efficiency and reproducibility, and the concentration of nifedipine in Procardia and Adalat 10- and 20-mg capsules was determined The methods evaluated were the needle puncture and squeeze method; the scissors method; the needle and syringe, one-hole method; the needle and syringe, two-hole method; and the capsule in syringe barrel method. The liquid content of 10 Adalat 10-mg capsules was removed by each method, the volume was determined by the weight and specific gravity of the nifedipine liquid, and the mean volumes of nifedipine liquid were compared. A stepwise procedure for using the needle and syringe, one-hole method was developed. The mean nifedipine concentration in Procardia 10- and 20-mg capsules was determined by ultraviolet spectrophotometry by using 30 capsules of each brand and strength. The needle and syringe methods were the most reproducible and efficient procedures for obtaining a desired milligram dosage of nifedipine from the capsules. The two-hole method would be less practical in the clinical setting, however, because it is time consuming and cumbersome. The mean assayed nifedipine concentration in the Procardia and Adalat 10- and 20-mg capsules was within 10% of the concentration reported by the manufacturer for each specific product lot number. Based on reproducibility and efficiency, the needle and syringe methods are the best methods for quantitation of liquid nifedipine doses for patient administration. PMID- 2589352 TI - Situational theory of leadership. AB - The situational theory of leadership and the LEAD instruments for determining leadership style are explained, and the application of the situational leadership theory to the process of planning for and implementing organizational change is described. Early studies of leadership style identified two basic leadership styles: the task-oriented autocratic style and the relationship-oriented democratic style. Subsequent research found that most leaders exhibited one of four combinations of task and relationship behaviors. The situational leadership theory holds that the difference between the effectiveness and ineffectiveness of the four leadership styles is the appropriateness of the leader's behavior to the particular situation in which it is used. The task maturity of the individual or group being led must also be accounted for; follower readiness is defined in terms of the capacity to set high but attainable goals, willingness or ability to accept responsibility, and possession of the necessary education or experience for a specific task. A person's leadership style, range, and adaptability can be determined from the LEADSelf and LEADOther questionnaires. By applying the principles of the situational leadership theory and adapting their managerial styles to specific tasks and levels of follower maturity, the authors were successful in implementing 24-hour pharmacokinetic dosing services provided by staff pharmacists with little previous experience in clinical services. The situational leadership model enables a leader to identify a task, set goals, determine the task maturity of the individual or group, select an appropriate leadership style, and modify the style as change occurs. Pharmacy managers can use this model when implementing clinical pharmacy services. PMID- 2589353 TI - Ciprofloxacin: major advances in intravenous and oral quinolone therapy. Proceedings of a symposium. April 28 to 29, 1989, Naples, Florida. PMID- 2589354 TI - Comparative efficacy of ciprofloxacin versus josamycin in the treatment of acute, recurrent, or exacerbated bronchitis. PMID- 2589355 TI - Use of ciprofloxacin in cystic fibrosis patients. AB - In order to evaluate the clinical efficacy and safety of oral ciprofloxacin in the treatment of acute pulmonary exacerbations of cystic fibrosis and trace the possible development of resistance over time, three trials were conducted. In an open-label, uncontrolled trial, 25 courses of ciprofloxacin were administered to 16 patients. Efficacy and safety were assessed based on changes in short-term clinical scores, white blood cell counts, Pseudomonas aeruginosa counts in sputum, pulmonary function tests, and standard serum chemistries and urinalysis that were performed before therapy, weekly during therapy, at the end of therapy, and at a seven-day follow-up visit after therapy. In an open-label, randomized, controlled study, the efficacy and tolerance of oral ciprofloxacin were compared with those of intravenous tobramycin and azlocillin. In another study, the rate of susceptibility of P. aeruginosa isolated from cystic fibrosis patients during more than two years of clinical use was determined. In the uncontrolled trial, ciprofloxacin therapy was associated with clinical improvement in most cases with changes in short-term clinical score and forced expiratory volume in one second being statistically significant (p less than 0.05). Twenty-five patients were entered in the controlled trial with 12 patients in each treatment group being evaluable. The groups were comparable based on admitting demographic and disease characteristics, and no differences in therapeutic response or side effects were noted between the two treatments (p greater than 0.5). Bacterial susceptibility to ciprofloxacin has remained relatively stable over time. Based on these results as well as those from similar evaluations, ciprofloxacin appears to be efficacious in the treatment of acute pulmonary exacerbations in adults with cystic fibrosis, producing responses similar to those observed with standard intravenous antibiotic therapy. PMID- 2589356 TI - Ciprofloxacin in the treatment of legionellosis in critically ill patients including those cases unresponsive to erythromycin. PMID- 2589357 TI - Ciprofloxacin treatment of malignant external otitis. AB - The Ear, Nose, and Throat department of the Meir Hospital treated 91 patients with malignant external otitis during the past 16 years. The last 23 patients with malignant external otitis were treated with ciprofloxacin 750 mg twice daily, combined with local excision of the aural lesion. The records of 61 of our previous 68 patients who underwent surgery and were hospitalized and treated with an intravenous extended-spectrum penicillin and gentamicin for six to eight weeks, were analyzed. Twenty-one of 23 patients treated with ciprofloxacin were cured; therapy failed in two patients. Treatment averaged 16.8 days of hospitalization, and bacteriologic eradication was achieved after an average of 7.04 days, as compared with 49 and 15.3 days, respectively, in the group of patients with the intravenous treatment. The mean peak concentrations of ciprofloxacin in serum varied between 2.5 and 3.7 micrograms/ml, and the drug concentrations in different ear tissues were 0.2 to 13 micrograms/g. The treatment with ciprofloxacin was well tolerated with no significant side effects, whereas serious side effects were noted in 45.9 percent of the previous intravenously treated group. The concentrations of the drug in serum and ear tissues were higher than the average minimal inhibitory concentration for Pseudomonas aeruginosa. Use of ciprofloxacin treatment, combined with local excision of the aural lesion, will bring about healing of malignant external otitis in the majority of cases. Ciprofloxacin can be given on an ambulatory basis after a relatively short period of hospitalization. PMID- 2589358 TI - Efficacy of single-agent therapy for the treatment of acute pelvic inflammatory disease with ciprofloxacin. AB - A prospective, randomized, controlled, non-blind clinical trial was conducted to compare the efficacy of monotherapy with ciprofloxacin with that of a combination of clindamycin plus gentamicin in the treatment of patients with acute pelvic inflammatory disease. Pretreatment and post-treatment cervical culture specimens were obtained for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum. Pretreatment and post-treatment endometrial culture specimens were obtained for those organisms plus facultative and anaerobic bacteria. Minimal inhibitory concentrations were determined on all isolates by agar dilution. Clinical resolution of infection was seen in 31 of 33 (94 percent) ciprofloxacin-treated patients compared with 34 of 35 (97 percent) clindamycin/gentamicin-treated patients. N. gonorrhoeae was eradicated in all cases and C. trachomatis in 12 of 13 cases (92 percent). Ciprofloxacin appeared less effective than clindamycin/gentamicin in eradicating bacterial-vaginosis associated organisms from post-treatment culture specimens obtained from the endometrium. Comparable clinical response was seen with both regimens. The significance of persistent bacterial-vaginosis-associated organisms following ciprofloxacin therapy is unclear. However, since one goal of treatment of pelvic inflammatory disease should be to eliminate organisms from the upper genital tract, ciprofloxacin may not provide optimal single-agent therapy for pelvic inflammatory disease. PMID- 2589359 TI - Comparison of parenteral ciprofloxacin with clindamycin-gentamicin in the treatment of pelvic infection. AB - A prospective, randomized study of intravenous followed by oral ciprofloxacin compared with the combination of intravenous clindamycin and gentamicin was conducted in 122 women hospitalized with pelvic infections. Clinical diagnoses included endometritis (97 patients) and uncomplicated pelvic inflammatory disease (25 patients). Treatment successes for endometritis included 42 of 50 (84 percent) patients treated with ciprofloxacin compared with 35 of 47 (75 percent) treated with the clindamycin-gentamicin combination. Treatment successes for acute salpingitis included 10 of 10 (100 percent) treated with ciprofloxacin and 13 of 15 (87 percent) treated with clindamycin-gentamicin. Ciprofloxacin successfully eradicated Chlamydia trachomatis in 11 of 12 patients as did clindamycin-gentamicin in six of seven patients. In this study of pelvic infection, ciprofloxacin demonstrated efficacy comparable with the combination of clindamycin and gentamicin, and is effective against C. trachomatis. PMID- 2589360 TI - Intravenous and oral ciprofloxacin in the treatment of proven pelvic inflammatory disease. A comparison with doxycycline and metronidazole. PMID- 2589361 TI - Intravenous/oral ciprofloxacin versus ceftazidime in the treatment of serious infections. AB - Seventy-one adult patients with 72 infections were treated, by random selection, with intravenous/oral ciprofloxacin or intravenously administered ceftazidime. Twenty-seven additional patients with 29 infections who were not appropriate for random assignment were treated in an open study with intravenously administered ciprofloxacin only; the latter infections were generally more serious or were caused by ceftazidime-resistant organisms. The most common doses were ciprofloxacin, 200 mg intravenously and 500 mg orally every 12 hours and ceftazidime, 1 to 2 g intravenously every eight to 12 hours. Forty-seven ciprofloxacin-treated infections and 31 ceftazidime-treated infections were evaluable for determination of efficacy. Infections included lower respiratory tract (21 infections), urinary (37 infections), skin/soft tissue (14 infections), bacteremia/endocarditis (four infections), colitis (one infection), and mastoiditis (one infection). Median minimal inhibitory concentrations of ciprofloxacin and ceftazidime were, respectively: for Enterobacteriaceae, Haemophilus influenzae, and Branhamella catarrhalis, no more than 0.06 and no more than 0.25 micrograms/ml; for Pseudomonas aeruginosa, 0.25 and 4 micrograms/ml; for Enterococcus faecalis, 1 and more than 32 micrograms/ml; and for Staphylococcus aureus, 0.25 and 8 micrograms/ml. Ciprofloxacin, 200 mg intravenously, yielded mean serum concentrations 0.5 and eight hours post intravenous infusion of 2.3 and 0.7 micrograms/ml, respectively. Satisfactory clinical responses were achieved in 17 (81 percent) of 21 patients with intravenous/oral ciprofloxacin, 22 (71 percent) of 31 patients with ceftazidime, and 20 (77 percent) of 26 patients with intravenous ciprofloxacin. The most common treatment failures occurred in complicated skin/soft-tissue infections treated with intravenous/oral ciprofloxacin, complicated urinary tract infections treated with ceftazidime, and necrotizing P. aeruginosa pneumonia treated with intravenous ciprofloxacin; the pneumonia patients all had respiratory failure and had been previously unresponsive to treatment with other appropriate drugs. Serious adverse reactions were observed in three patients, seizures with intravenous ciprofloxacin in two patients, and Clostridium difficile diarrhea with ceftazidime in one patient. We conclude that sequential intravenous/oral ciprofloxacin and ceftazidime were comparable in efficacy and safety; the ability to change from intravenous to oral therapy is a major convenience. Intravenous ciprofloxacin was useful for more serious infections, often caused by ceftazidime resistant organisms. PMID- 2589362 TI - Randomized study of intravenous versus sequential intravenous/oral regimen of ciprofloxacin in the treatment of gram-negative septicemia. PMID- 2589364 TI - Intravenous ciprofloxacin therapy in severe infections. AB - Fifty evaluable patients (34 men and 16 women; mean age, 47 years) with severe infections were given intravenous ciprofloxacin (200 mg every 12 hours) for a mean of 14 days. Therapy was continued with oral ciprofloxacin 500 to 750 mg every 12 hours in 34 cases for a mean of 57 days. The sources of the infections were bone and joint (26 patients), respiratory tract (10 patients), urinary tract (four patients), soft tissue (four patients), abdominal (three patients), bacteremia of unknown origin (two patients), and right-sided endocarditis (one patient). Fifteen patients (30 percent) were bacteremic. Causative organisms included Pseudomonas aeruginosa (32 patients), other gram-negative bacilli (18 patients), and gram-positive cocci (nine patients). Minimal inhibitory concentrations ranged between 0.03 and 1 microgram/ml. Mean peak serum concentrations were 1.58 micrograms/ml (intravenous) and 2 micrograms/ml (oral); mean trough serum concentrations were 0.23 micrograms/ml (intravenous) and 0.32 micrograms/ml (oral). Serum bactericidal activity values achieved after intravenous and oral therapy were similar. Response to therapy was evaluated separately in patients with or without osteomyelitis. In 30 patients with infections other than osteomyelitis, clinical cure was achieved in 27 (90 percent), and therapy failure occurred in three patients. In the 20 remaining patients with osteomyelitis, 15 (75 percent) had a satisfactory response, with apparent cure after a mean follow-up of 11 months, whereas five had therapeutical failure (P. aeruginosa became resistant in four of them). Overall, no major adverse effects were encountered. Superinfection by a resistant P. aeruginosa was observed in three patients. Intravenous ciprofloxacin is an effective and safe agent for the therapy of severe infections caused by susceptible organisms. PMID- 2589363 TI - Safety and efficacy of intravenous ciprofloxacin in the treatment of selected infections. AB - A prospective study of the efficacy and safety of intravenous ciprofloxacin in the treatment of selected infections was conducted at the Ochsner Medical Institutions from October 1986 through March 1987. Thirty-three patients were treated with intravenous ciprofloxacin at dosages of either 200 mg or 300 mg every 12 hours. The mean duration of therapy was 12 days. Various infection sites were treated and included urinary tract, respiratory tract, skin and skin structure, bone, intra-abdominal, blood, and heart. Clinical improvement was noted in 20 of the 26 evaluable patients (77 percent). Fifty-two bacterial pathogens were isolated with eradication of 37 (71 percent). There was bacteriologic persistence in seven patients (13 percent). Superinfection occurred in one patient; however, no recurring or reinfecting organisms were isolated. Adverse events related to ciprofloxacin occurred in six patients and were primarily mild. Overall, ciprofloxacin was useful in the treatment of a variety of infections, and adverse events were minimal. PMID- 2589365 TI - Sequential intravenous/oral therapy with ciprofloxacin in severe infection. PMID- 2589366 TI - Ciprofloxacin in patients with bacteremic infections. The Spanish Group for the Study of Ciprofloxacin. AB - The efficacy and safety of ciprofloxacin in the treatment of 68 episodes of bacteremia were studied. Patients were treated intravenously (30 cases), orally (13 cases), or with sequential intravenous/oral therapy (25 cases). Intravenous doses ranged from 200 to 400 mg per day and oral doses ranged from 1,000 to 1,500 mg per day. According to the criteria of McCabe and Jackson, 39 cases had nonfatal and 29 had ultimately fatal underlying diseases. The clinical condition of patients at the start of therapy was critical or poor in 40 cases and fair or good in 28. Sixty-four of the 68 episodes of bacteremia were monomicrobial and the remaining four were polymicrobial. The causative micro-organisms were: Escherichia coli (18 episodes), Pseudomonas aeruginosa (13 episodes), Acinetobacter sp. (10 episodes), Salmonella sp. (seven episodes), Enterobacter sp. (six episodes), Proteus sp. (four episodes), Serratia sp. (four episodes), Haemophilus influenzae (three episodes), Klebsiella sp. (three episodes), Staphylococcus aureus (2 episodes), and Morganella morganii (two episodes). Overall clinical efficacy of ciprofloxacin was 94 percent (64 of 68 patients). Bacteremia persisted in four patients (failure rate of 6 percent). Five organisms persisted: Acinetobacter sp. (two patients), P. aeruginosa (one patient), Enterobacter sp. (one patient), and Serratia sp. (one patient). Side effects were phlebitis associated with intravenous administration (four cases), dizziness (four cases), and superinfection (six cases). Superinfecting organisms and sites were as follows: Enterococcus faecalis, wound (2 cases); Candida sp., urinary tract infection (one case); Acinetobacter anitratus (ciprofloxacin resistant), urinary tract infection (one case); Staphylococcus epidermidis, blood (one case); and Clostridium perfringens, blood (one case). Ciprofloxacin administered either intravenously, orally, or intravenously followed by the oral route is effective therapy in the treatment of severe bacteremic infections. PMID- 2589367 TI - Effect of the abscess environment on the antimicrobial activity of ciprofloxacin. AB - The present studies were conducted to identify factors in human purulent material that might limit or enhance the activity of ciprofloxacin against bacteria causing suppurative infection. Ciprofloxacin, imipenem, and ampicillin were tested with regard to binding or inactivation by pus. The bactericidal activity of ciprofloxacin and imipenem were tested against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, or Staphylococcus aureus in human pus with a pH of 6.0 incubated at 37 degrees C under aerobic or anaerobic conditions. The effect of single or combination drug therapy with 20 mg/kg of ciprofloxacin, imipenem, or rifampin given every 12 hours was tested against E. coli or P. aeruginosa in polymicrobic murine abscesses that had been produced by subcutaneous injection of either of those organisms mixed with Bacteroides fragilis and autoclaved human stool. Antibiotic levels and the number of bacteria surviving in pus were quantitated. Therapy of subcutaneous abscesses was delayed 72 hours to test drug efficacy against organisms in well-established infections. Levels of ampicillin, imipenem, or ciprofloxacin were reduced from 10 micrograms/ml to 3.1 +/- 4.0, 2.7 +/- 3, or 5.8 +/- 2 micrograms/ml, respectively, after incubation in eight pus specimens for 24 hours at 37 degrees C. Ampicillin levels were reduced to less than 1 microgram/ml in four pus specimens containing beta-lactamase. Imipenem levels were undetectable in two specimens and were 0.2 micrograms/ml in one specimen. Ciprofloxacin binding to pus supernate or sediment appeared to be explained by its binding to the deoxyribonucleic acid (DNA) present in pus. Activity of 5 micrograms/ml of ciprofloxacin against four E. coli or K. pneumoniae strains in pus in vitro was greater than that of twofold higher concentrations of imipenem. The bactericidal activity of ciprofloxacin and imipenem were comparable but substantially reduced against S. aureus and P. aeruginosa in pus. Ciprofloxacin alone or regimens combining ciprofloxacin with rifampin or rifampin plus imipenem reduced the number of E. coli in polymicrobic subcutaneous abscesses but had little effect on P. aeruginosa in polymicrobic abscesses. The anaerobic abscess milieu appeared to inhibit the growth of P. aeruginosa. Ciprofloxacin activity in abscess fluid did not appear to be adversely affected by acid pH, aerobic or anaerobic conditions of incubation, the abscess constituents, or the binding of ciprofloxacin to the DNA in pus. Ciprofloxacin was bound to DNA of bacterial or human origin. Binding by pus was reversible, and binding to DNA extracts of pus was blocked by pretreatment of extracts with deoxyribonuclease but not by pretreatment with ribonuclease.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2589368 TI - Intravenous and sequential intravenous and oral ciprofloxacin in the treatment of severe infections. PMID- 2589369 TI - Clinical study of intravenous and oral ciprofloxacin in complicated bacterial infections. PMID- 2589370 TI - Intravenous and oral ciprofloxacin treatment of 52 infections. PMID- 2589371 TI - Ciprofloxacin treatment of sternal wound infections following open heart surgery. PMID- 2589372 TI - Ciprofloxacin in the treatment of gram-negative bacillary meningitis. AB - Gram-negative bacillary meningitis (typically caused by E. coli, K. pneumoniae, P. aeruginosa, A. calcoaceticus, and others) has been associated with head trauma, neurosurgical operations, pathologic anastomosis with nasal cavity, and CSF rhinorrhea, as well as with impaired host defenses. Intravenous ciprofloxacin was given to 20 patients with gram-negative bacillary meningitis. The dose of ciprofloxacin was 200 mg by intravenous infusion, over 30 minutes, every 12 hours for 10 days. Two patients also received intravenous cefotaxime and penicillin G. All patients were monitored daily. Of 20 patients, 18 had cure and therapy failed in two. Because relatively low concentrations of ciprofloxacin are achieved in the CSF, the drug should be used in the treatment of gram-negative bacillary meningitis only if the MICs of the causative pathogen and the ciprofloxacin concentration in CSF can be followed. A randomized, controlled study is needed to compare the efficacy of intravenous ciprofloxacin with standard antibiotic therapy in the treatment of this disease. PMID- 2589373 TI - Intravenous ciprofloxacin versus cefotaxime prophylaxis during transurethral surgery. PMID- 2589374 TI - Single-dose preoperative prophylaxis in transurethral surgery. Ciprofloxacin versus cefotaxime. PMID- 2589375 TI - Intravenous ciprofloxacin for infections in cancer patients. AB - One hundred forty-seven cancer patients were treated with intravenously administered ciprofloxacin, 200 mg every eight hours, as initial therapy for febrile episodes. Thirty patients (20 percent) were neutropenic (less than 1,000 neutrophils/mm3) at the onset of infection. The overall clinical response rate was 78 percent, 73 percent for neutropenic patients and 79 percent for patients with adequate neutrophil counts. Favorable responses were observed in 19 of 25 patients with bacteremia, 29 of 44 patients with pneumonia, 16 of 18 patients with skin and soft-tissue infection, nine of nine patients with urinary tract infection, 10 of 11 patients with upper respiratory infection, and 26 of 34 patients with fever of undetermined origin. Gram-negative infections were associated with a response rate of 94 percent, gram-positive infections with a response rate of 75 percent, and polymicrobial infections with a response rate of 82 percent. Resistance to ciprofloxacin did not develop and no superinfections were seen. Toxicity was minor except in one patient, in whom a seizure developed. Intravenously administered ciprofloxacin is effective and safe therapy for many infections in cancer patients. PMID- 2589376 TI - Treatment of sepsis in patients with neoplastic diseases with intravenous ciprofloxacin. AB - Hospitalized patients with sepsis caused by ciprofloxacin-susceptible organisms were treated with intravenous ciprofloxacin 300 mg every 12 hours. Patients were followed closely for side effects and adverse reactions as well as for their response to therapy. Culture specimens and laboratory parameters including serum chemistry profile, complete blood cell count, and urinalysis were obtained before, during (every four to five days), and after ciprofloxacin therapy. Antimicrobial susceptibility of bacterial isolates was determined by the microtiter technique. Patients were considered to have had a successful outcome if satisfactory improvement in signs and symptoms of infection occurred as well as bacteriologic cure, such as eradication of organisms from the blood during and after treatment. Of 30 septic episodes in 30 patients, 27 episodes were considered evaluable. Two septic episodes occurred in patients who were neutropenic (absolute neutrophil count less than 1,000/mm3). The sources of the 27 septic episodes were intra-abdominal (12 patients), indwelling intravenous access devices (11 patients), urinary tract (three patients), and skin/soft tissue (one patient). Of the 27 evaluable episodes, 24 (88.9 percent) had a completely successful outcome; three (11.1 percent) had a partially successful outcome. Partial successes included the occurrence of a Klebsiella pneumoniae reinfection in one patient, superinfection with Listeria monocytogenes in another patient with the concurrent development of a highly ciprofloxacin-resistant K. pneumoniae, and the recovery of a ciprofloxacin-resistant Pseudomonas aeruginosa during therapy in a third patient who also had superinfection due to Candida albicans. There were minimal ciprofloxacin-related adverse reactions and side effects. Although ciprofloxacin was generally well tolerated with minimal side effects and adverse reactions and was efficacious in the treatment of serious septicemic infections caused by gram-negative aerobic bacilli, the development of a resistant K. pneumoniae and the recovery of a resistant P. aeruginosa during therapy in two cases are of concern and deserve further investigation. PMID- 2589378 TI - New oral and parenteral quinolones. A summary. PMID- 2589377 TI - Intravenous ciprofloxacin as empirical treatment of febrile neutropenic patients. AB - A randomized study of treatment with ciprofloxacin combined with benzylpenicillin (CB) versus a standard regimen of netilmicin combined with piperacillin (NP) as first-line empiric therapy was conducted in febrile neutropenic patients. Ninety six patients were evaluable for determination of efficacy: 50 patients received CB and 46 patients received NP. There was no significant difference between the two groups in terms of age or primary diagnosis. Overall clinical response rate at the end of therapy was 66 percent for CB and 65 percent for NP. Microbiologic assessment revealed more pathogens eradicated by CB (64 percent) and fewer persisting (4 percent) than in the NP group (52 percent eradicated, 13 percent persisting). Only 10 percent of patients in the CB group had treatment-related adverse reactions as opposed to 28 percent of the NP-treated patients; these were predominantly renal impairment and were likely to have been due to the aminoglycoside. Staphylococcus epidermidis was the most commonly isolated pathogen, accounting for 38 percent of all isolates and 30 percent of all patients in whom treatment failed. Although streptococci accounted for 18 percent of the isolated pathogens, no treatment failures or superinfections were due to these organisms. This indicates an advantage of combining ciprofloxacin with benzylpenicillin. We conclude that the CB regimen is as effective as the NP treatment and is associated with fewer side effects. PMID- 2589380 TI - Combination chemotherapy with ciprofloxacin for infection with Mycobacterium tuberculosis in mouse models. PMID- 2589379 TI - An update on the efficacy of ciprofloxacin in animal models of infection. AB - Although animal models of infection are associated with certain limitations in interpretation, properly performed studies provide important information for evaluating the efficacy of new antimicrobial agents in the treatment of human disease. The antibacterial efficacy of the newer quinolones, particularly ciprofloxacin, has undergone extensive evaluation in several animal models. Efficacy has been demonstrated in animal models of pneumonia, endocarditis, meningitis, skin and soft-tissue infections, septic arthritis, burn wound sepsis, empyema, intra-abdominal abscess, osteomyelitis, prostatitis, sinusitis, urinary tract infection, chronic gastroenteritis, granuloma pouch infection, and Pseudomonas septicemia. More recent studies have evaluated the efficacy of ciprofloxacin in animal models of tuberculosis and syphilis, as well as in infections caused by the intracellular pathogens Salmonella typhimurium, Legionella pneumophila, and Listeria monocytogenes. PMID- 2589381 TI - Ciprofloxacin: toxicologic evaluation of additional safety data. AB - Long-term ciprofloxacin toxicology studies, additional data on arthorpathogenic effects, embryotoxicity studies in monkeys, and further results on central nervous system/interaction toxicology are presented. In the long-term studies of rats and mice, ciprofloxacin was given as food admixture in concentrations up to 5,000 ppm for 24 and 21 months, respectively. This treatment regimen did not result in any systemic toxicity and also did not give any indication of a tumorigenic effect of ciprofloxacin. In a study of juvenile dogs to investigate development of arthropathogenic lesions using magnetic resonance imaging techniques, an increase in width of the recessus suprapatellaris occurred only in those dogs in which marginal effects developed. Thus, this technique may be a suitable method to monitor juvenile patients receiving ciprofloxacin. Ciprofloxacin was also studied for its potential to act as an abortifacient when given orally or parenterally to cynomolgus monkeys. The data obtained did not give any indication of teratogenicity or embryolethality, and mean patterns of progesterone were similar between routes of administration, dose groups, and controls. Finally, data are presented that demonstrate that central nervous system interaction toxicity between quinolones and nonsteroidal anti-inflammatory drugs can be observed in rats only at therapeutically irrelevant high dose levels. PMID- 2589382 TI - Ciprofloxacin intravenous dose variance. AB - Following different intravenous dosages of ciprofloxacin in volunteers, only limited variation in serum concentrations have been reported using volunteers in both single- and multiple-dose studies. In patients, a greater variability in serum concentrations was reported during intravenous ciprofloxacin treatment. This was also the case in patients with varying degrees of renal insufficiency. However, no report exists of nonmeasurable ciprofloxacin serum concentrations during intravenous treatment in patients. PMID- 2589383 TI - Combination effects of ciprofloxacin, clindamycin, and metronidazole intravenously in volunteers. AB - Despite the broad antibacterial spectrum of ciprofloxacin, most anaerobic organisms are resistant to the drug, whereas several gram-positive organisms are only moderately susceptible. Thus, in some clinical situations, combined treatment with ciprofloxacin and metronidazole or clindamycin could be useful. Therefore, the pharmacokinetics and serum bactericidal activities of ciprofloxacin in combination with clindamycin or metronidazole were investigated using a randomized crossover study design in 10 healthy volunteers. Ciprofloxacin (200 mg) was administered alone and in combination with clindamycin (600 mg) or metronidazole (500 mg); all drugs were given intravenously over 30 minutes. Serum and urine concentrations of the substances were measured using standard methods (high-performance liquid chromatography or gas chromatography). Blood samples for determination of serum bactericidal activity against five different aerobic and two anaerobic bacterial species (a total of 58 strains) were obtained one hour and six hours after drug infusion. All values were statistically analyzed by use of the Student t test. PMID- 2589384 TI - Pharmacokinetics of three newer quinolones in pregnant and lactating women. AB - Sixty pregnant women with fetuses affected by beta-thalassemia major underwent termination of gestation induced by amniocentesis and intrauterine instillation of prostaglandin F2 alpha between 19 and 25 weeks. Pharmacokinetics of ciprofloxacin in maternal blood and amniotic fluid were studied after two doses of ciprofloxacin (200 mg intravenously every 12 hours), after two doses of pefloxacin (400 mg intravenously every 12 hours), and after two doses of ofloxacin (400 mg intravenously every 12 hours). Twenty patients were studied in each group. The ranges of mean maternal serum and amniotic fluid levels were as follows: ciprofloxacin in maternal serum 0.01 to 0.28 micrograms/ml, in amniotic fluid 0.1 to 0.13 micrograms/ml; pefloxacin in maternal serum 2.65 to 4.31 micrograms/ml, in amniotic fluid 1.97 to 2.74 micrograms/ml; and ofloxacin in maternal serum 0.07 to 0.68 micrograms/ml, in amniotic fluid 0.13 to 0.25 micrograms/ml. Three groups of lactating women (10 women in each), were given three doses of 750 mg ciprofloxacin orally, 400 mg pefloxacin orally, and 400 mg ofloxacin orally. Serum and milk samples were obtained simultaneously at two, four, six, nine, 12, and 24 hours after dosage administration. The mean breast milk levels of ciprofloxacin at the corresponding time intervals were 3.79, 2.26, 0.86, 0.51, 0.20, and 0.02 micrograms/ml. The mean breast milk levels of pefloxacin were 3.54, 3.43, 2.93, 2.24, 1.79, and 0.88 micrograms/ml, and of ofloxacin, 2.41, 1.91, 1.25, 0.64, 0.29, and 0.05 micrograms/ml. It is concluded that all studied quinolones penetrate the placenta and are found in amniotic fluid at low concentrations and at much higher levels in breast milk. Because of the potential for quinolones to cause arthropathy in juvenile animals, their use should be avoided in pregnant and lactating women. PMID- 2589385 TI - Efficacy and safety of higher-dose intravenous ciprofloxacin in severe hospital acquired infections. AB - In an open prospective study, 54 patients in an interdisciplinary, operative, anesthesiologic intensive care unit were treated with intravenous ciprofloxacin for life-threatening infections. Secondary nosocomial pneumonias were the predominant infection in most patients. A total of 88 causative pathogens were isolated from 50 patients. The most commonly isolated organism was Pseudomonas aeruginosa; Serratia marcescens, Staphylococcus aureus, and Enterobacter sp. were also isolated. Pathogens could not be detected in four patients (three patients with pneumonia, one patient with urinary tract infection). Ciprofloxacin was administered intravenously, either 400 mg every 12 hours or, after a loading dose of 600 mg every 12 hours on Day 1, 400 mg every 12 hours on successive treatment days. A total of 44 patients were treated parenterally, four orally. An additional six patients received ciprofloxacin in both dosage forms as sequential therapy. Serum ciprofloxacin levels were determined by high-performance liquid chromatography in 17 patients. The serum concentrations and the elimination half life were in accordance with values already published for parenteral doses of 200 and 500 mg ciprofloxacin. Ciprofloxacin clearance was linear even at the high dose (600 mg every 12 hours loading dose) and no cumulative effect was observed. Clinical outcome was very good. Cure was achieved in 21 patients, and clinical improvement occurred in 23 (favorable clinical response rate, 82 percent). Two patients did not respond to therapy, and eight patients were not evaluable. Adverse effects occurred in 12 patients: transient elevation of liver enzymes (seven patients), temporary increase in serum creatinine levels (two), convulsions (two), and exanthem (one). The treatment of severe infections in intensive care patients with higher doses of parenteral ciprofloxacin appears to be considerably more effective than therapy with the doses of intravenous ciprofloxacin recommended to date. Therefore, these preliminary results are the subject of an ongoing double-blind study. PMID- 2589386 TI - Pharmacokinetics of ciprofloxacin in young (healthy volunteers) and elderly patients, and concentrations in prostatic fluid, seminal fluid, and prostatic adenoma tissue following intravenous administration. PMID- 2589388 TI - Gastrointestinal secretion of ciprofloxacin. Evaluation of the charcoal model for investigations in healthy volunteers. PMID- 2589387 TI - Respiratory tract penetration of ciprofloxacin. PMID- 2589389 TI - Absorption differences of ciprofloxacin along the human gastrointestinal tract determined using a remote-control drug delivery device (HF-capsule). AB - The single-dose absorption kinetics of ciprofloxacin in different regions of the human gastrointestinal tract were investigated using a remote-control drug delivery device (HF-capsule). Doses of 180 to 200 mg ciprofloxacin (as a lactic acid solution) were placed in the HF-capsule and administered to four healthy male adults. The position of the HF-capsule in the gastrointestinal tract was checked via radiographic examination. The release of the solution from the HF capsule was induced by a radio signal. In each volunteer, the solution was released into five different regions of the gastrointestinal tract: the stomach (B), jejunum (C1), ileum (C2), ascending colon (D1), and descending colon (D2). Two control runs (A1, A2), involving oral administration of the solution, were used as a reference for calculation of area under the curve. The oral administration of a conventional 250-mg tablet (A3) was also studied. The plasma concentration of ciprofloxacin and urine concentrations of ciprofloxacin, desethylene- (M1), sulfo- (M2), and oxociprofloxacin (M3) were determined fluorimetrically by high-performance liquid chromatography. Intraindividual comparisons indicated a progressive decrease in the amount of ciprofloxacin absorbed (100 percent = mean of AUCA1 and AUCA2) from the jejunum (-61 percent, median), ileum (-75 percent), colon ascendens (-90 percent), and colon descendens (-95 percent). Absolute amounts of renally excreted ciprofloxacin and metabolites decreased due to the reduced absorption of ciprofloxacin, but the metabolite pattern was unchanged. It is concluded that the main absorption site for ciprofloxacin is the upper part of the intestinal tract (duodenum, jejunum). PMID- 2589390 TI - Ciprofloxacin pharmacokinetics in critically ill trauma patients. AB - The steady-state pharmacokinetics of ciprofloxacin 200 mg intravenously every 12 hours was examined in 10 critically ill trauma patients. The mean parameter estimates for total clearance, renal clearance, non-renal clearance, and volume of distribution were 30.08 liters/hour/1.73 m2, 16.62 liters/hour/1.73 m2, 13.46 liters/hour/1.73 m2, and 2.10 liters/kg. Although the mean values were similar to those previously reported, significant individual differences were observed, with the coefficient of variation ranging from 41 to 61 percent. Non-renal clearance appeared to have a bimodal distribution. The dosage studied appeared to provide adequate serum concentration profiles to treat most pathogens found in infected trauma patients. However, the use of higher doses and more frequent dosing may be required to treat patients with Staphylococcus aureus and Pseudomonas aeruginosa infections. PMID- 2589391 TI - Cyclosporine (cyclosporin A) pharmacokinetics in renal transplant patients receiving ciprofloxacin. AB - The effects of ciprofloxacin administration on the pharmacokinetic parameters and biologic tolerance of cyclosporine (cyclosporin A) were determined in primary renal transplant patients. This study was performed in 10 patients (four women and six men) ranging in age from 26 to 64 years and body weight ranging from 46 to 88 kg. Ciprofloxacin therapy was started eight to 48 days (mean, 21 days) after transplantation, whereas the cyclosporine therapy was administered for seven to 48 days (mean, 18 days) post-transplant. Both ciprofloxacin and cyclosporine were administered every 12 hours. The mean cyclosporine dosage was 2.4 mg/kg per day, adjusted to obtain blood concentrations within the recommended range (i.e., 100 to 200 ng/ml). The ciprofloxacin dosage was 750 mg orally twice daily for all patients. A pharmacokinetic study of cyclosporine was performed in each patient the day before starting ciprofloxacin treatment and after the 13th ciprofloxacin administration (i.e., Day 7 of ciprofloxacin therapy). Cyclosporine concentrations were measured in whole blood by a specific high-performance liquid chromatography method and the following parameters were determined: minimal and maximal blood concentrations, area under the curve from zero to 12 hours, total body oral clearance, mean residence time, and elimination half life. Concurrently administered medications and serum creatinine values were recorded. No statistically significant difference was noted between the cyclosporine pharmacokinetic parameters before and during ciprofloxacin treatment. Serum creatinine levels were increased in four of 10 patients, but the increase was not considered related to ciprofloxacin treatment. In conclusion, it appears that ciprofloxacin can be administered to renal transplant patients without risk of interacting cyclosporine or enhancement of cyclosporine nephrotoxicity. Additional cyclosporine blood level monitoring is not particularly valuable in this setting. PMID- 2589392 TI - Pharmacokinetics of orally administered ciprofloxacin in abdominal surgery. PMID- 2589393 TI - Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. AB - The inhibitory effects of ciprofloxacin and other quinolone derivatives on the hepatic cytochrome P450-dependent metabolism of caffeine have been investigated in humans. In vivo studies involved an intraindividual comparison of the single dose kinetics of caffeine before and during quinolone administration in 12 healthy men. Changes of enzymatic caffeine degradation by the quinolones were studied in vitro using human liver microsomes from three donors. Enoxacin and pipemidic acid markedly prolonged caffeine elimination in vivo. A positive correlation exists between the doses of enoxacin or ciprofloxacin and the prolongation (increases) in the caffeine elimination half-life. Decreases in caffeine elimination, using doses of ciprofloxacin in the upper part of the recommended dose range, were approximately 1.5-fold in comparison with untreated control subjects, whereas in the case of enoxacin there was a sixfold change. In vitro results with enoxacin, ofloxacin, ciprofloxacin, and pipemidic acid show a competitive inhibition (Dixon plots) of caffeine 3-demethylation. Ciprofloxacin and enoxacin showed the strongest inhibitory effects in vitro, whereas ofloxacin had the lowest inhibitory effect. These results are qualitatively reflected in the in vivo results; however, the clinical effects may be dependent on pharmacokinetic disposition of the quinolone and this could explain the weak inhibitory action of ciprofloxacin in vivo. PMID- 2589394 TI - Resistance development to fluoroquinolones in Europe. AB - We did not observe an increase in quinolone-resistant strains in recent years despite a dramatic increase in drug usage. P. aeruginosa strains should be carefully monitored in the future since a trend to increased MICs seems obvious. Epidemiologic data on resistance have to be evaluated carefully, and special interest must be focused on the breakpoint in relation to the normal distribution of MICs. Conclusions can be drawn only if the increased numbers of strains are clearly separated from the normal distribution. PMID- 2589395 TI - Infectious disease management of adult leukemic patients undergoing chemotherapy: 1982 to 1986 experience at Stanford University Hospital. AB - PURPOSE: The purpose of this study was to determine the recent incidence of infection and to evaluate antimicrobial usage among adult leukemic patients undergoing chemotherapy for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) at Stanford University Hospital. PATIENTS AND METHODS: The records of 142 adult patients from a consecutive series of 226 induction or consolidation/maintenance chemotherapy courses for AML or ALL between 1982 to 1986 were reviewed retrospectively. Data were analyzed to compare the infectious disease complications and antimicrobial usage for patients receiving identical chemotherapy for a specific phase of leukemia treatment. Evaluation for each chemotherapy course included assessments for the following: compliance with criteria for initiating antibiotics, incidence of infection that was documented by culture or clinical criteria, predictive value of surveillance cultures, incidence of superinfection, survival outcomes, antimicrobial usage, antibiotic-related adverse effects, and cost for antibiotics and diagnostic studies. RESULTS: Antimicrobials were employed in 190 (84%) of 226 chemotherapy courses. Broad-spectrum antibiotics were regularly begun within the first five days of admission and they were continued for an average of 3.5 weeks until the granulocyte count was greater than 1,000/microL after discontinuation of chemotherapy. There were no differences in the types of infection or outcomes among the patient groups. There was only a 37% rate of documented infections by culture or clinical signs among these patients during their entire hospital stay. Bacterial infections, especially those caused by coagulase-negative staphylococci in patients with Hickman catheters, accounted for 93% of the episodes. Viral and fungal infections accounted for 4% and 3% of documented cases, respectively, and occurred more than 10 days after the institution of broad-spectrum antibiotic therapy. A total of 922 different antimicrobials were employed in 190 courses (average 4.9 per course). The rationale for excessive usage and multiple changes was a persistent or intermittent fever, rather than documented infection(s). This practice led to usage of more broad-spectrum and expensive antibiotics. Further analyses indicate that the greater number of antibiotics employed correlated with apparent increased toxicity, especially renal and hepatic adverse reactions. These toxicities were associated with higher rates of fatal outcomes, i.e., 12 (39%) of 31 patients died with antibiotic-associated hepatic and/or renal insufficiency, compared with 12 (7.5%) of 159 patients who died without antibiotic-associated organ damage. CONCLUSION: Excessive antibiotic usage and multiple antibiotic changes among adult leukemic patients undergoing chemotherapy appear to increase the risks of adverse hepatic and renal effects and death. Furthermore, this practice leads to use of more broad-spectrum and expensive antibiotics... PMID- 2589396 TI - Risk factors for nosocomial candidemia: a case-control study in adults without leukemia. AB - PURPOSE: The purpose of this study was to define risk factors for nosocomial candidemia in adult patients without leukemia at a tertiary care medical center. PATIENTS AND METHODS: All patients with nosocomial candidemia between August 1, 1981, and October 31, 1984, were included if they met strict selection criteria and did not have acute or chronic leukemia. For each case, one control was selected from among patients admitted during the same month/year and matched for hospital service and duration of hospitalization up to the first blood culture that grew Candida species. Logistic regression was used to obtain estimates of risk after simultaneously controlling for other variables. RESULTS: Candida albicans caused 24 of the 48 fungemias studied. The risk factors identified included the presence of a central line (odds ratio, 26.4; 95% confidence interval, 1.5 to 451.1); bladder catheter (13.0 1.3 to 131.4); two or more antibiotics (25.1, 2.1 to 318); azotemia (22.1, 2.2 to 223.2); transfer from another hospital (21.3, 1.7 to 274.5); diarrhea (10.2, 1.03 to 101.4); and candiduria (27.0, 1.7 to 423.5). A prior surgical procedure was associated with lowered risk (0.1, 0.01 to 0.9), suggesting perhaps that medical service patients are at higher risk than those on surgical services. Because total parenteral nutrition was always administered by means of a central line, it could not be shown to increase the risk over that conferred by a central line alone. CONCLUSIONS: This study has defined seven major risk factors for nosocomial candidemia. These findings should facilitate development of rational approaches to preventing infection and may assist clinicians in identifying those patients in whom this life-threatening complication is likely to occur. PMID- 2589398 TI - Oxygen transport and oxygen consumption during supplemental oxygen administration in patients with chronic obstructive pulmonary disease. AB - PURPOSE: Oxygen consumption (VO2) is independent of oxygen delivery (DO2) above a critical level of DO2. VO2 may become dependent on DO2 when oxygen demand exceeds oxygen supply. We studied DO2 VO2, and exercise capacity in 12 stable, ambulatory patients with chronic obstructive pulmonary disease (COPD) receiving ambient air and 26% oxygen to ascertain whether VO2 is dependent on DO2 in this patient sample. PATIENTS AND METHODS: An exercise protocol consisting of a symptom limited, low-level treadmill test with progressive increments in workload was performed twice, once with patients breathing ambient air and once with patients breathing 26% oxygen. Expired gas, arterial and mixed venous blood values, and recordings of systemic and pulmonary artery pressures were obtained after a 10 minute period of rest (while standing) and during the last minute of each three minute exercise level. RESULTS: Five patients had an increase in exercise capacity, defined as an increase in the maximal VO2 greater than 25%, using supplemental oxygen. In these patients, oxygen delivery increased from 10.9 +/- 3.4 to 13.8 +/- 4.7 mL/minute/kg (p = 0.008) at rest and from 16.2 +/- 5.0 to 24.7 +/- 2.7 mL/minute/kg (p = 0.046) during exercise with supplemental oxygen administration. VO2 increased from 0.329 +/- 0.065 to 0.436 +/- 0.109 L/minute (p = 0.029) at rest and from 0.776 +/- 0.275 to 1.119 +/- 0.482 L/minute (p = 0.048) during exercise. Three of these five patients had an arterial oxygen pressure greater than 55 mm Hg at rest. Seven patients had little or no increase in exercise capacity with supplemental oxygen. This patient group had no increase in VO2 at rest. The DO2 failed to increase at rest despite an increase in arterial oxygen content because of a reduction in cardiac output. CONCLUSION: These data demonstrate that DO2 may fail to increase in some patients with COPD and resting or exertional hypoxemia when supplemental oxygen is administered because of a reduction in cardiac output; that patients who fail to increase their DO2 are less likely to increase exercise capacity; and that some stable, ambulatory patients with COPD who do not qualify for supplemental oxygen at rest by current standards may have inadequate DO2 to meet physiologic needs. PMID- 2589397 TI - Prospective evaluation of a Candida antigen detection test for invasive candidiasis in immunocompromised adult patients with cancer. AB - PURPOSE: Serologic tests to detect invasive candidiasis generally have been unreliable. We prospectively evaluated the clinical utility of a new, promising commercial latex particle agglutination test (i.e., Cand-Tec, Ramco Laboratories, Inc., Houston, Texas). This assay detects Candida antigens in serum. PATIENTS AND METHODS: We examined the reliability of Cand-Tec to diagnose invasive candidiasis in 142 consecutive in-patients intensively treated with chemo-radiation therapy. Serum samples were collected at admission and then weekly, until the patients' death or hospital discharge. Evaluation for clinical utility was done using various reference titers. Twenty-nine patients had invasive candidiasis whereas 113 patients did not have documented invasive candidal infections. RESULTS: At a titer of 1:8, the Cand-Tec test had sensitivity of 38%, specificity of 90%, positive predictive value of 50%, and negative predictive value of 85%. Weekly use of the Cand-Tec test did not improve early detection of invasive candidiasis, providing only a mean interval of 0.4 day from the first positive Cand-Tec result to a definitive diagnosis of invasive candidiasis by blood culture, tissue biopsy, or autopsy. In addition, surveillance cultures from the oropharynx or stool were not helpful in identifying those patients who would develop an invasive fungal infection. CONCLUSION: In the context of current clinical management strategies for suspected fungal infection, the Candida antigen detection assay (Cand-Tec) is not a reliable method for diagnosis of deep candidiasis in neutropenic patients. Until better methods of early detection are available, patients at high risk for the development of invasive candidiasis should continue to receive empiric antifungal agent therapy. PMID- 2589399 TI - The anemia of chronic disease: spectrum of associated diseases in a series of unselected hospitalized patients. AB - PURPOSE: Previous studies of the anemia of chronic disease (ACD) have generally begun with patients afflicted with one of the classical underlying diseases such as rheumatoid arthritis. The clinical spectrum of ACD has not been thoroughly examined. We hypothesized that many patients have an anemia with the characteristics of ACD but do not have one of the infectious, inflammatory, or neoplastic disorders usually associated with ACD. We therefore evaluated a series of consecutive, unselected, anemic patients admitted to a county hospital. PATIENTS AND METHODS: All patients admitted to the medicine ward service of a county hospital were screened for anemia (hematocrit less than 40% in men, less than 37% in women). Additional laboratory data were collected on all anemic patients, except those with active gastrointestinal bleeding, hemolytic disease, or leukemia or multiple myeloma. The patients were divided into three groups on the basis of serum values indicating iron distribution: iron deficiency (serum ferritin less than 10 ng/mL), ACD (serum iron less than 60 micrograms/dL and serum ferritin more than 50 ng/mL), and all others (non-ACD). The hospital records of the patients in the latter two groups were reviewed and their diagnoses recorded. RESULTS: Seven patients with iron deficiency were not considered further. Ninety patients with ACD were compared with 75 patients with non-ACD. The anemia in ACD patients was more severe than most authors describe. The mean hematocrit was 31%, and 20% of patients had hematocrits below 25%. The anemia was usually normocytic (mean red cell volume [MCV] 86 fL), but 21% had an MCV less than 80 fL. The level of saturation of serum iron-binding capacity was quite low in ACD (mean 15%) and was normal in non-ACD (mean 31%). Renal insufficiency was common in both groups; serum creatinine values were more than 2 mg/dL in 31% of patients with ACD and 20% of non-ACD patients. Sixty percent of patients with ACD had a principal diagnosis that fell into the infectious, inflammatory, and neoplastic categories commonly associated with ACD. Renal insufficiency was the major diagnosis in 16%, and the principal diagnosis in 24% was a disease not commonly considered to be associated with ACD. In non-ACD patients, the principal diagnosis was an infectious, inflammatory, or neoplastic disease in 55%, renal insufficiency in 9%, and another disease in 36%. CONCLUSIONS: When ACD was defined by the abnormalities of iron distribution, which are its most consistent and widely accepted characteristics, the spectrum of associated diseases was much broader than the traditional categories of infectious, inflammatory, and neoplastic disorders, and the overlap with non-ACD was large. Until the etiologic and pathogenetic mechanisms of ACD are better understood, a flexible and inclusive view of this disorder seems appropriate. PMID- 2589400 TI - Analysis of plasma histamine levels in patients with mast cell disorders. AB - PURPOSE: The use of plasma histamine determinations as a screening tool to distinguish patients with recurrent unexplained anaphylaxis, flushing, or both from those with mastocytosis has never been evaluated. This retrospective study was designed to determine if plasma histamine levels can be used as a screening test. PATIENTS AND METHODS: Values of plasma histamine levels, measured using a sensitive radioenzymatic assay, from 41 patients with mastocytosis, 26 patients with recurrent unexplained anaphylaxis, and 76 normal subjects were statistically analyzed to determine diagnostic usefulness and accuracy. Patients with mastocytosis were subdivided into four smaller groups on the basis of clinical and histopathologic findings: (1) isolated urticaria pigmentosa, (2) indolent systemic mastocytosis, (3) mastocytosis with dysmyelopoiesis, and (4) lymphadenopathic mastocytosis with eosinophilia. RESULTS: The distribution of plasma histamine values among patients with unexplained anaphylaxis strongly resembled that among the normal subjects (p greater than 0.50, Smirnov test), whereas patients with mastocytosis tended to show moderate to marked elevations above the upper limit of normal (617 pg/mL). The geometric mean plasma histamine levels in mastocytosis subgroups 2, 3, and 4 were found to be quite similar (1,085, 1,976, and 1,433 pg/mL; p greater than 0.50, F-test); moreover, each mean level was significantly greater than those of the normal subjects and of patients with unexplained anaphylaxis (p less than 0.01, Scheffe multiple comparison test). Analysis of the 27 sets of plasma histamine values collected on patients with indolent systemic mastocytosis revealed that the earliest value observed fell below 617 pg/mL in eight patients (30%). A similar analysis applied to the two earlier values indicated that both values would fall below 617 pg/mL in 9% of the patients. Data in four patients with mastocytosis demonstrated a diurnal variation in plasma histamine, with the highest values observed in the early morning (approximately 2:00 A.M.) and the lowest values in the afternoon (approximately 2:00 P.M.). CONCLUSIONS: We conclude that, on average, patients with mastocytosis have elevated plasma histamine levels, whereas patients with unexplained anaphylaxis have plasma histamine levels within the normal range during asymptomatic periods; that plasma histamine levels in patients with mastocytosis exhibit a diurnal variation; and that plasma histamine determinations alone are not useful to screen patients for mastocytosis. PMID- 2589402 TI - An innocent tale. PMID- 2589403 TI - Human ehrlichiosis associated with cerebrospinal fluid pleocytosis: a case report. PMID- 2589401 TI - Challenge with gliadin induces eosinophil and mast cell activation in the jejunum of patients with celiac disease. AB - PURPOSE: The aim of this study was to clarify the role of eosinophils and mast cells in the small bowel in celiac disease. PATIENTS AND METHODS: Patients with celiac disease (n = 10) were investigated by perfusion of a closed jejunal segment. The concentrations of certain granule constituents from eosinophils, eosinophil cationic protein (ECP), and from mast cells/basophils, histamine, were measured and the jejunal secretion rates of these cellular markers were calculated. RESULTS: Compared with findings in healthy control subjects (n = 14), increased secretion rates were observed under basal conditions in patients with histopathologically active celiac disease. Gliadin, administered by perfusion to the jejunal segment, induced a fourfold increase in ECP secretion and a twofold increase of histamine secretion in patients with celiac disease (n = 7), but did not influence the secretion rates of these substances in healthy controls (n = 3). The secretion rate of ECP started to increase 20 minutes after challenge of the perfused segment with gliadin and reached maximum levels 40 minutes later. The secretion rate of histamine started to increase 40 minutes after gliadin administration. Concurrently with these inflammatory events, the secretion of albumin was doubled as a sign of increased mucosal leakage. CONCLUSION: These data indicate that eosinophils and mast cells are both involved in the early gliadin-induced reactions of the small intestine, and suggest that these cells are effector cells participating in the celiac lesion of the mucosa. PMID- 2589404 TI - Recurrent cryptogenic hemoptysis associated with bronchial artery-pulmonary artery anastomoses and cystic lung disease. PMID- 2589405 TI - Splenosis mimicking an intra-abdominal malignancy. PMID- 2589406 TI - Granulomatous infiltration of the talus and abnormal vitamin D and calcium metabolism in a patient with sarcoidosis: successful treatment with hydroxychloroquine. PMID- 2589407 TI - Pentamidine-induced severe hyperkalemia. PMID- 2589408 TI - Thrombotic thrombocytopenic purpura as the first manifestation of human immunodeficiency virus infection. PMID- 2589409 TI - Polycythemia secondary to hepatic hemangioma with abnormal secretion of erythropoietin. PMID- 2589410 TI - Acute pancreatitis induced by erythromycin. PMID- 2589411 TI - Amanita poisoning. PMID- 2589413 TI - Add two transfusion steps? PMID- 2589412 TI - Are universal precautions changing the "nurture" of obstetric nursing? PMID- 2589414 TI - You can capture personal histories. PMID- 2589415 TI - Standing up for America's homeless. PMID- 2589416 TI - How nurses are helping the homeless. PMID- 2589417 TI - Should states be setting standards for agency staffing? PMID- 2589419 TI - Controlling cholesterol with diet. PMID- 2589418 TI - Cholesterol. Interpreting the new guidelines. PMID- 2589420 TI - Controlling cholesterol with drugs. PMID- 2589421 TI - Helping patients take cholesterol-lowering drugs. PMID- 2589422 TI - Water intoxication. PMID- 2589423 TI - Recognizing the psychiatric water intoxicator. PMID- 2589424 TI - Going into business as a nurse. PMID- 2589425 TI - Florida jobfocus. Florida's bounty. PMID- 2589426 TI - Southeast jobfocus. Southern hospitality. PMID- 2589427 TI - My trips over the language barrier. PMID- 2589428 TI - Low amniotic pressure in oligohydramnios--is this the cause of pulmonary hypoplasia? AB - The mechanism by which oligohydramnios produces lung hypoplasia is not understood. The current theory that extrinsic compression of the fetal thorax causes hypoplasia, either by inhibiting breathing movements or by squeezing out lung liquid, is not supported by observational or experimental data, or by our finding of decreased amniotic pressure around the fetus in oligohydramnios. We hypothesize that lung hypoplasia results from excess loss of lung liquid because of a reduction in amniotic pressure, and hence an increase in the alveolar amniotic pressure gradient. The magnitude of this increased pressure gradient is calculated to exceed the small standing tracheal pressure; thus low amniotic pressure overcomes the normal laryngeal retentive mechanisms and allows a larger quantity of lung liquid to escape. In the prevention of pulmonary hypoplasia, a role is suggested for the instillation of artificial amniotic fluid to restore normal amniotic pressure. PMID- 2589429 TI - Meconium aspiration syndrome: intrapartum and neonatal attributes. AB - To identify the fetus and newborn at risk for meconium aspiration syndrome the perinatal characteristics of 238 infants delivered through meconium-stained amniotic fluid were prospectively examined. All infants with meconium-stained amniotic fluid were routinely suctioned with a DeLee apparatus before tracheal intubation and suctioning. The type and presence of meconium in the trachea, neonatal breathing before intubation, and Apgar scores were recorded in the delivery room. Intrapartum fetal monitoring data were collected for 80% (190/238) of the mothers and umbilical artery pH for 74% (177/238) of the newborns. Despite suctioning with a DeLee apparatus and endotracheal suctioning, meconium was present in the trachea in 87/238 (37%) and meconium aspiration syndrome developed in 22 (9.2%). A total of 73% of newborns who had meconium aspiration syndrome were delivered through thick meconium. Thick meconium, the presence of fetal tachycardia, and absence of intrapartum fetal cardiac accelerations identified the fetus at high risk for meconium aspiration syndrome. The presence of these monitoring findings and thick meconium should alert obstetricians to the possibility of a fetus that requires intervention. Low umbilical artery pH, Apgar scores less than 5, and meconium in the trachea further characterized the newborn at high risk for meconium aspiration syndrome. The combination of these findings may best identify the infant delivered through meconium-stained amniotic fluid who requires close observation for meconium aspiration syndrome. PMID- 2589430 TI - Perinatal outcome in very preterm births with twin-twin transfusion syndrome. AB - We retrospectively studied 48 pairs of twin gestations delivered between 24 and 28 weeks' gestation from 1975 to 1986 at Vanderbilt University Medical Center. The incidence of fetofetal transfusion syndrome was 20%, more than double the incidence previously reported in large series of twin deliveries that encompassed a wider gestational age range. The overall mortality was 55%, and mortality for the fetofetal transfusion group was 70%, whereas a subset of the fetofetal transfusion group, those without weight discordancy, had a mortality rate of 75%. Our findings suggest that traditional reliance on ultrasonographic criteria for diagnosis of fetofetal transfusion will not detect 40% of such cases. The poor outcome data suggest a need for innovative approaches to diagnosis and treatment. PMID- 2589431 TI - Changing outcome of extremely premature infants (less than or equal to 26 weeks' gestation and less than or equal to 750 gm): survival and follow-up at a tertiary center. AB - Management of extremely premature infants is controversial because limits of viability are not established. From 1981 to 1987, 175 infants were admitted to the neonatal intensive care unit at Minneapolis Children's Medical Center with gestational ages less than or equal to 26 weeks and birth weights less than or equal to 750 gm. To assess current prognosis and to analyze trends over time, survival data and developmental characteristics of surviving infants were reviewed. During the study period, antenatal obstetric management was assertive, with liberal indications for tocolysis and expectant management for preterm prolonged membrane rupture, with the goal of delivery of infants in a nonasphyxiated condition. Ninety-one percent of infants were inborn and were managed aggressively after birth with full neonatal support. Survival increased from 21% in 1981-1982 to greater than 50% in 1986-1987 and occurred as early as 23 weeks' gestation. Seventy-one percent of all deaths occurred within 48 hours of birth, and late death (greater than 28 days) was uncommon. At follow-up, 23% of survivors were impaired, a proportion that remained relatively constant during the study period. Improvements in survival were not associated with an increased proportion of impaired infants. Survival with good outcome is attainable at gestational ages and birth weights previously considered nonviable. For obstetricians, neonatologists, and parents, knowledge of such current data can play an important role in making appropriate management decisions for both mother and infant. PMID- 2589432 TI - Cervical dilation: a comparison of Lamicel and Dilapan. AB - A randomized prospective double-blind study compares the dilatation achieved with Lamicel and Dilapan synthetic dilators in the setting of second-trimester elective abortions. A total of 51 patients with estimated gestational ages of 13 to 16 weeks had either Lamicel dilators or Dilapan dilators placed approximately 20 hours before dilation and evacuation. The placement and removal were by someone other than the operator. The operator then recorded the number of the Pratt dilator at which resistance was first met. The mean for the Lamicel group was French size 38.5 +/- 6.4. The mean for the Dilapan group was French size 50.4 +/- 9.6. In the Dilapan group there were six patients for whom cervical resistance was never reached. The results indicate a significantly greater dilatation was achieved with Dilapan dilators. This correlation was also noted within the subsets of nulliparous and parous patients. PMID- 2589433 TI - Predicting maximal oxygen uptake from treadmill testing in trained and untrained women. AB - This study was conducted to develop an equation to predict maximal oxygen uptake from exercise time during a standardized treadmill test in women aged 29 to 75 years before and after aerobic training. Treadmill tests were administered to 181 women with measurement of maximal oxygen uptake, and an equation predicting maximal oxygen uptake was derived: maximal oxygen uptake (ml.kg-1.min-1) = 10.34 + 1.29 (exercise time), r = 0.88, standard error of the estimate = 2.1, p less than 0.0001. Thirty-three women were retested after 6 and 12 months of aerobic exercise training. Maximal oxygen uptake was predicted from the equation developed and compared with the measured values at 6 and 12 months. The predicted and measured maximal oxygen uptake values after training were not significantly different. These results indicate that it is possible to predict maximal oxygen uptake for clinical purposes with a single equation from exercise time in untrained and trained women across a wide range of ages. PMID- 2589434 TI - Mechanisms that subserve estradiol's induction of increased prolactin concentrations: evidence of amplitude modulation of spontaneous prolactin secretory bursts. AB - Estradiol stimulates hyperprolactinemia in human beings and in experimental animals by mechanism(s) that remain largely undefined. We have tested the hypothesis that estrogen modulates episodic and rhythmic prolactin release. To this end we studied six postmenopausal women by repetitive venous sampling basally and on days 1, 5, 10, and 30 after intravaginal placement of an estradiol impregnated polymeric silicone (Silastic) ring. Computerized analysis of episodic prolactin pulsatility revealed that estrogen amplified prolactin pulse amplitude threefold without changing prolactin pulse frequency. Fourier analysis disclosed heightened amplitudes of specific ultradian rhythms, and deconvolution analysis demonstrated a sevenfold increase in the mass of prolactin secreted per pulse with no change in its half-life. We conclude that estradiol selectively augments the amplitude of episodic prolactin pulsatility, amplifies ultradian rhythms, and increases the mass of prolactin released per secretory burst. PMID- 2589435 TI - Reproductive outcome after anesthesia and operation during pregnancy: a registry study of 5405 cases. AB - To define the risk of adverse reproductive outcomes after nonobstetric operations during pregnancy, we linked data from three Swedish health care registries, the Medical Birth Registry, the Registry of Congenital Malformations, and the Hospital Discharge Registry, for the years 1973 to 1981. Adverse outcomes examined were the incidences of (1) congenital anomalies, (2) stillborn infants, (3) infants dead at 168 hours, and (4) infants with very low and low birth weights. There were 5405 operations in the population of 720,000 pregnant women (operation rate, 0.75%). The incidences of congenital malformations and stillbirths were not increased in the offspring of women having an operation. However, the incidences of very-low- and low-birth-weight-infants were increased; these were the result of both prematurity and intrauterine growth retardation. The incidence of infants born alive but dying within 168 hours also was increased. No specific types of anesthesia or operation were associated with increased incidences of adverse reproductive outcomes. The cause of these outcomes was not determined. PMID- 2589436 TI - Placenta percreta induced uterine rupture and resulted in intraabdominal abortion. AB - Acute abdomen and shock are diagnosed in a 21-year-old primigravid patient at 23 weeks' gestation. Laparotomy revealed a 7 to 8 cm rupture on the fundus of the uterus and a 450 gm dead fetus in the abdominal cavity. PMID- 2589437 TI - Cervical cancer in Jewish women. AB - Because of the known low incidence rate of cervical cancer in Jewish women, less than appropriate attention has been focused on this type of malignancy in Jewesses. We have summarized our experience with 144 cases of cervical cancer diagnosed during 25 years in South Israel. In recent years a remarkable, although not statistically significant, increase in the number of patients with cervical cancer could be observed. Only two of ten patients were diagnosed at preinvasive stage. In contrast with previous reports we did not find women of Asian and African origin to be overrepresented, but patients from these origins were more often diagnosed at a higher stage than were patients of European origin. Adenocarcinoma accounts for almost 19% of the cervical cancer in premenopausal women. A very low rate of early detection of cervical cancer and a trend of rising incidence of cervical cancer in Jewish women urgently require a reevaluation of health care policy. Large-scale screening programs, perhaps initially in defined high-risk groups are needed. PMID- 2589438 TI - Colposcopic findings and intraepithelial neoplasia in diethylstilbestrol-exposed offspring. The Dutch experience. AB - Data from two regional diethylstilbestrol clinics for colposcopic evaluation of young women with a history of diethylstilbestrol exposure in utero are presented: A total of 224 subjects with a well-documented history were enrolled in this study. Structural anomalies of the cervix and vagina were found in 30%. Vaginal epithelial changes were colposcopically observed in 65%, including vaginal adenosis in 22%. The prevalence rate of abnormal cytologic findings in the study group was 9%. In half of these patients a low-grade intraepithelial neoplasia of the cervix and vagina was found. It was concluded that colposcopy in diethylstilbestrol-exposed offspring in inexperienced hands can result in many unnecessary biopsies. Therefore colposcopic examination should be performed by expert colposcopists in referral diethylstilbestrol centers. PMID- 2589439 TI - Cordocentesis in the investigation of fetal erythropoiesis. AB - Fetal blood hemoglobin concentration and erythrocyte, reticulocyte, and erythroblast counts were determined in umbilical cord samples obtained from 194 pregnancies at 17 to 40 weeks' gestation. The fetuses sampled were undergoing prenatal diagnosis and were subsequently found not to be affected by the condition investigated. The hemoglobin concentration and erythrocyte count increased linearly with gestation from respective means of 11 gm/dl and 2.5 x 10(12)/L at 17 weeks to 15.5 gm/dl and 4.5 x 10(12)/L at 40 weeks. The erythroblast count decreased exponentially from a mean of 83/100 leukocytes at 17 weeks to 4/100 leukocytes at 40 weeks. The reticulocyte count decreased linearly from a mean of 27.5 x 10(9)/L or 10/100 red blood cells at 17 weeks to 17.5 x 10(9)/L or 4/100 red blood cells at 40 weeks. PMID- 2589440 TI - Preeclampsia: an endothelial cell disorder. AB - Despite intense study preeclampsia remains enigmatic and a major cause of maternal and fetal morbidity and mortality. Most investigative efforts have focused on the hypertensive component of this disorder with reduced attention given to other equally important characteristics. Increased sensitivity to pressor agents and activation of the coagulation cascade occur early in the course of preeclampsia, often antedating clinically recognizable disease. Inasmuch as endothelial cell injury reduces the synthesis of vasorelaxing agents, increases the production of vasoconstrictors, impairs synthesis of endogenous anticoagulants, and increases procoagulant production, these cells are likely to be implicated in the pathophysiology of preeclampsia. Indeed, evidence of endothelial cell injury is provided by the most characteristic morphologic lesion of preeclampsia, glomerular endotheliosis. Additional support for this hypothesis is derived from reports that indicate increased levels of circulating fibronectin (which can be released from injured endothelial cells) and increased factor VIII antigen present in the blood of preeclamptic women. More recently, direct evidence of activities that injure endothelial cells in vitro and increase the contractile sensitivity of isolated vessels has been presented. We propose that poorly perfused placental tissue releases a factor(s) into the systemic circulation that injuries endothelial cells. The changes initiated by endothelial cell injury set in motion a dysfunctional cascade of coagulation, vasoconstriction, and intravascular fluid redistribution that results in the clinical syndrome of preeclampsia. PMID- 2589441 TI - Antagonism of antihypertensive drug therapy in pregnancy by indomethacin? AB - Two women with preeclampsia treated with pindolol and propranolol became profoundly hypertensive when indomethacin was added because of premature contractions. The interaction of nonsteroidal antiinflammatory agents and beta blockers and their role in the control of blood pressure in obstetrics are discussed. Indomethacin should not be given to pregnant patients with hypertension treated with beta-blockers. PMID- 2589442 TI - CA 125 as an independent prognostic factor for survival in patients with epithelial ovarian cancer. AB - Serum CA 125 levels (upper normal value less than 35 U/ml) determined before surgery and 3 months after surgery were evaluated as independent prognostic factors for survival in patients with epithelial ovarian carcinomas. In 163 women preoperative serum levels of CA 125 (p = 0.13) gave no additional information with regard to the relationship of survival prognosis to histologic grade (p = 0.04) and to the diameter of residual tumor mass (p = 0.03). In 132 patients serum CA 125 levels were also determined 3 months after surgery and reflected the effectiveness of the first two cycles of postoperative cytotoxic treatment. At that time CA 125 was the strongest independent prognostic factor for survival (p = 0.0006 Cox model), as compared with histologic grade (p = 0.06), International Federation of Gynecology and Obstetrics stage (p = 0.15), and diameter of residual tumor mass (p = 0.66). Therefore, we concluded that serum CA 125 levels determined 3 months after surgery can identify a high-risk population among patients with epithelial ovarian carcinomas for whom a more aggressive or more intensive treatment might be beneficial. PMID- 2589443 TI - Plasma amino acids in appropriate- and small-for-gestational-age fetuses. AB - The fetal plasma amino acid profiles of 28 small-for-gestational-age fetuses were established in umbilical venous blood samples obtained by cordocentesis and the values were compared with those of 62 appropriate-for-gestational age fetuses. In the appropriate-for-gestational-age group fetal levels were significantly correlated with but were higher than the maternal levels, which indicates that amino acids are actively transported by the placenta. In the small-for gestational-age group, the fetal plasma concentration and the fetomaternal ratio of essential amino acids was decreased and this decrease was significantly correlated with the degree of fetal hypoxemia. There was a variable response (e.g., alanine was increased, whereas serine and tyrosine were decreased) involved with nonessential amino acids. In umbilical venous hypoxemia the plasma ratio of nonessential/essential amino acids was increased, and the maternal plasma concentrations of both essential and nonessential amino acids were increased. These findings suggest that in uteroplacental insufficiency there is intrauterine starvation. PMID- 2589444 TI - Effect of nutrient intake on premenstrual depression. AB - We examined the occurrence and coincidence of depressed mood and excessive carbohydrate intake in 19 patients who claimed to suffer from severe premenstrual syndrome and in nine control subjects, all as inpatients, during the early follicular and late luteal phases of their menstrual cycles. Mood was assessed with the Hamilton Depression Scale and an addendum that evaluated fatigue, sociability, appetite, and carbohydrate craving. Calorie and nutrient intakes were measured directly. The subjects with premenstrual syndrome significantly increased calorie intake during the late luteal phase (from 1892 +/- 104 to 2395 +/- 93 kcal, mean +/- SEM); carbohydrate intake increased by 24% from meals and by 43% from snacks. Protein intake failed to change, whereas intake of fat, a fixed constituent of all of the test foods, rose in proportion to calorie intake. The Hamilton Depression Scale and addendum scores rose from 2.0 +/- 0.5 to 21.2 +/- 0.8 (Hamilton Scale) and from 0.5 +/- 0.5 to 10.2 +/- 0.6 (addendum) among subjects with premenstrual syndrome during the luteal phase but failed to change among the controls (2.1 +/- 0.8 to 2.4 +/- 0.8, and 0.4 +/- 0.3 to 0.6 +/- 0.3). Consumption of a carbohydrate-rich, protein-poor evening test meal during the late luteal phase of the menstrual cycle improved depression, tension, anger, confusion, sadness, fatigue, alertness, and calmness scores (p less than 0.01) among patients with premenstrual syndrome. No effect of the meal was observed during the follicular phase or among the control subjects during either phase. Because synthesis of brain serotonin, which is known to be involved in mood and appetite, increases after carbohydrate intake, premenstrual syndrome subjects may overconsume carbohydrates in an attempt to improve their dysphoric mood state. PMID- 2589445 TI - Immunosuppression in pregnant women infected with human immunodeficiency virus. AB - One hundred two pregnant women at high risk of infection with the human immunodeficiency virus (62 who were drug abusers and 40 of Haitian origin) were prospectively examined for immunologic changes during and after pregnancy. Among the 63 human immunodeficiency virus-negative women, levels of CD4+ (helper) cells fell to a nadir at 8 weeks before delivery and rose rapidly just before delivery. The level of CD8+ (cytotoxic/suppressor) cells rose slowly from midpregnancy to delivery. Among the 37 human immunodeficiency virus-positive pregnant women, levels of CD4+ cells fell during pregnancy (except for a transient weak increase just before delivery) and did not recover in the postpartum period. Levels of CD8+ cells were consistently higher in human immunodeficiency virus-positive than human immunodeficiency virus-negative women. Post partum the CD8+ cells in human immunodeficiency virus-negative women stabilized at delivery levels, whereas they increased greatly in human immunodeficiency virus-positive women. The loss of CD4+ cells in human immunodeficiency virus-positive women appeared to be faster during pregnancy than in the postpartum period. These data support the hypothesis that pregnancy may accelerate human immunodeficiency virus-induced depletion of CD4+ cells and increase the risk of acquired immunodeficiency syndrome. PMID- 2589446 TI - Fetal death from chlamydial infection across intact amniotic membranes. AB - We report a case of a fetal death at 34 weeks' gestation with intact membranes. An autopsy confirmed intrauterine pneumonia as a result of Chlamydia trachomatis. Staining of the lung tissue with a direct fluorescein-conjugated Chlamydia specific monoclonal antibody assay revealed a pattern typical of a Chlamydia trachomatis infection. This case supports the thesis that Chlamydia crosses fetal membranes and produces disease. PMID- 2589447 TI - Prognostic significance of steroid receptors measured in primary metastatic and recurrent endometrial carcinoma. AB - Forty-two cases of recurrent and 14 cases of advanced clinical stage (III and IV) endometrial carcinoma are presented, in which progesterone and estrogen receptors from the metastatic sites were measured. Mean survival time (time from recurrence or, in advanced stages, from the time of diagnosis to death or last follow-up), mean total survival time (time from diagnosis to death or last follow-up), and mean time to recurrence (time from diagnosis of primary tumor to the time of recurrence) were positively correlated with positive progesterone and estrogen receptor status and with histologic grade of tumor. No correlation was found with age, clinical stage, depth of myometrial invasion, or site of metastasis. However, when multiple variables were considered with the Cox regression model, the combination most highly correlated with survival included progesterone receptor, grade of tumor, and site of metastasis (pelvis vs. other sites). All differences were statistically significant (p less than 0.05). We conclude that measurement of progesterone and estrogen receptors in metastatic or recurrent endometrial tumors may be used as an additional prognostic variable. PMID- 2589448 TI - Immunohistochemical expression of TAG-72 in normal and malignant endometrium: correlation of antigen expression with estrogen receptor and progesterone receptor levels. AB - TAG-72 is a tumor-associated antigen that is expressed by secretory endometrium and most endometrial adenocarcinomas. We used immunohistochemical techniques to quantitate expression of TAG-72, estrogen receptor, and progesterone receptor in 21 normal endometria and 44 endometrial adenocarcinomas. In normal cycling endometrial glands, TAG-72 expression was related inversely to expression of receptors for estrogen and progesterone. This suggests that TAG-72 expression in normal endometrium may be hormonally regulated. Ninety-one percent of endometrial adenocarcinomas expressed immunohistochemically detectable TAG-72. The magnitude of TAG-72 expression did not correlate with other known prognostic factors in endometrial cancer such as histologic grade, depth of myometrial invasion, surgical stage, or steroid receptor status. The production of TAG-72 by most endometrial adenocarcinomas may represent nonspecific expression by cells that have dedifferentiated. PMID- 2589450 TI - Hemodynamic changes during twin pregnancy. A Doppler and M-mode echocardiographic study. AB - Serial hemodynamic investigations were performed in 10 women with twin pregnancies at 20, 24, 28, 32, and 36 weeks' gestation and at 6 months after delivery. Cardiac output was measured by Doppler and cross-sectional echocardiography at the aortic, pulmonary, and mitral valves. Cardiac chamber size and ventricular function were investigated by M-mode echocardiography. The hemodynamic results were compared with those of 13 women with singleton pregnancies. Mean Doppler cardiac output was increased at 20 weeks of twin pregnancy (7.63 L/min) and showed no significant change during the remainder of pregnancy, but fell to 5.07 L/min after delivery. This increase was significantly greater than that recorded during singleton pregnancy, because of a relatively greater increase in heart rate. Twin pregnancy was associated with a significantly greater increase in left atrial dimension, but the increases in left ventricular dimensions, wall thickness, and function were comparable to those recorded in singleton pregnancy. PMID- 2589449 TI - Successful treatment in two women with antiphospholipid antibodies and refractory pregnancy losses with intravenous immunoglobulin infusions. AB - In two women with antiphospholipid antibodies and recurrent fetal losses refractory to usual treatments, therapy consisting of aspirin, heparin, and intravenous gamma-globulin infusions was successful. Production of antiphospholipid antibodies was not suppressed. The transient decrease in anticoagulant activity noted in one case was not reproduced in vitro and was probably not physiologically important. PMID- 2589451 TI - The improving outcome of triplet pregnancies. AB - During the period 1975 to 1988, 78 triplet pregnancies that reached a gestational age greater than or equal to 20 weeks were treated in our department--a prevalence of 1/849 deliveries. A total of 69 (88%) of the pregnancies occurred after treatment with ovulation-induction agents. The most common complication of pregnancy was premature contractions. Elective cervical cerclage neither prolonged gestation nor decreased fetal loss. The mean gestational age at delivery was 33.2 weeks + 3.8 weeks and 86% of the patients were delivered of premature infants. The perinatal and neonatal mortality rates were 93/1000 and 51/1000, respectively. Our results show a higher proportion of low Apgar scores and respiratory disorders in the third vaginally delivered infants. Follow-up of very low birth weight infants revealed four infants (10.5%) with severe neurologic handicaps. Results of this study suggest that cesarean section is the preferred mode of delivery in triplet pregnancies. Maternal, fetal, and neonatal risks of triplet gestations are relatively low and compare favorably with recent reports on twin pregnancies. PMID- 2589452 TI - Semen predictors of in vitro fertilization and embryo cleavage. AB - In vitro fertilization treatment for male infertility is not very successful because fertilization is known to be affected by semen quality. Information on fertilizing ability may provide prognostic information for couples contemplating such treatment. The purpose of this study was to identify semen variables that would predict fertilization and embryo cleavage. Sperm was prepared by the swim up method before insemination of oocytes obtained by laparoscopy after ovulation induction. Routine semen analysis and the hypoosmotic swelling test for assessment of sperm membrane integrity were performed on aliquots of prepared sperm. Logistic regression and receiver-operator characteristic curve analyses were performed to determine the overall best-fitting model and discriminatory level of variables that would predict cleavage. The results indicate that after the swim-up procedure, at least 10 million sperm/ml, capable of undergoing swelling in hypoosmotic medium, are necessary to increase the likelihood of in vitro fertilization and cleavage. PMID- 2589453 TI - Integration of the transabdominal technique into an ongoing chorionic villus sampling program. AB - Data are presented on 869 patients undergoing chorionic villus sampling procedures by one of two sampling techniques: 544 by a transcervical catheter aspiration method and 325 by a transabdominal two-needle aspiration method. The transcervical approach was the only procedure used in the first 330 cases, at which time the transabdominal technique was incorporated into our program. After an initial learning curve in the first 100 procedures the transcervical fetal loss rate stabilized at 2.7%, the number of patients requiring more than one catheter insertion decreased to 11%, and tissue weights greater than or equal to 10 mg were obtained in 88% of cases. The fetal loss rate for transabdominal chorionic villus sampling was 2.6%, indicating the addition of this new method did not significantly alter the fetal loss rate. Transabdominal chorionic villus sampling had an overall success rate of 99%, with only one insertion of the guide needle required for 98% of patients. Tissue weights of greater than or equal to 10 mg were obtained in 99% of cases. These results demonstrate that the transabdominal procedure can be rapidly and effectively incorporated by an operator already experienced with transcervical chorionic villus sampling. Since several contraindications exist for either chorionic villus sampling method, the availability of both techniques at a single center greatly enhances the ability to offer first-trimester fetal diagnosis to a majority of patients. PMID- 2589454 TI - Continuous fetal monitoring with a pulse oximeter: a case of cord compression. AB - We have adapted a pulse oximeter to monitor fetal oxygen saturation during labor. In a case of acute cord compression the pulse oximetry reading dropped below 20% and this change in fetal oxygen saturation preempted changes in the cardiotocograph. PMID- 2589455 TI - Clinical experience with phenytoin prophylaxis in severe preeclampsia. AB - In North America, magnesium sulfate is the traditional treatment for severe preeclampsia and eclampsia. Its use has been strongly criticized, in that it acts peripherally with no central effect and maternal and neonatal complications are well known. Phenytoin, the mechanism of action of which is clear, seems a logical alternative. Our aim was to develop a safe, practical, effective regimen with the use of phenytoin. In this prospective, descriptive study four dosage regimens were investigated in 104 patients. The initial regimens produced unexpected and unacceptable side effects in comparison with the nonpregnant population. The final regimen (15 mg/kg intravenously, given as 10 mg/kg initially then 5 mg/kg 2 hours later) provided therapeutic levels and had minimal maternal and perinatal side effects. No seizures occurred after its correct usage. This regimen is simple, safe, effective, and provides ongoing anticonvulsant coverage in the postpartum period. We suggest that phenytoin may represent a suitable alternative anticonvulsant in this condition. PMID- 2589457 TI - Human uterus-derived growth substances for rat bone cells and fibroblasts. AB - The effects of extracts from normal human uteri on tritiated thymidine incorporation and cell number were studied in primary cultures of isolated fetal rat calvarial osteoblasts and fetal rat skin fibroblasts. In this study crude uterine extracts were shown to stimulate tritiated thymidine incorporation into cellular deoxyribonucleic acid in osteoblast-like and fibroblast-like cell cultures above controls levels. This effect, which began after 6 hours, was maximal after 24 hours of incubation. In addition, the number of osteoblast-like and fibroblast-like cells increased above control levels after 1, 3, and 5 days of incubation. The above effects were dose-dependent, and maximal stimulation of uterine extracts was comparable with the stimulation achieved by 10% fetal bovine serum. The degree of stimulation by uterine extracts, expressed as percent above controls, was not dependent on the concentration of fetal bovine serum in cell culture medium. The above results are consistent with the view that uterine extracts contain mitogen(s) for bone cells and fibroblasts. These mitogens could play an important role in bone physiology and uterine pathophysiology. PMID- 2589456 TI - Effects of thromboxane synthetase inhibition on maternal-fetal homeostasis in gravid ewes with ovine pregnancy-induced hypertension. AB - Simultaneous maternal indirect blood pressure measurements, electronic fetal heart rate monitoring, and ultrasonographic biophysical profile testing were used to assess maternal-fetal homeostasis in gravid ewes during gestational days 127 to 134 (term 146), during a 72-hour fast, and during treatment with thromboxane synthetase inhibitors CGS13080 and CGS12970. Seventy-five percent of the ewes (12 of 16) developed clinical signs of ovine pregnancy-induced hypertension, including maternal hypertension and fetal depression. In three untreated hypertensive ewes, pregnancy was terminated by spontaneous premature delivery, and one maternal death occurred after an eclamptic seizure. All nine ewes treated with one of the two thromboxane synthetase inhibitors responded to therapy with decreases in blood pressure and resolution of fetal depression. These nine ewes completed gestation, and were delivered at term. These data indicate that therapy with thromboxane synthetase inhibitors in this animal model of preeclampsia results in profoundly beneficial effects and suggest that further studies of thromboxane synthetase inhibitors are warranted in preeclampsia. PMID- 2589458 TI - Human alpha- and beta-calcitonin gene-related peptides are vasodilators in human chorionic plate vasculature. AB - Calcitonin gene-related peptide receptors are known to be present in the placenta. We studied the effect of alpha- or beta-calcitonin gene-related peptide or carrier on human chorionic plate arteries preconstricted with angiotensin II. Both forms of calcitonin gene-related peptides evoked dose-dependent relaxation, the magnitude of which was proportional to the initial response to angiotensin II. PMID- 2589459 TI - In vitro uterine response to tetramethylpyrazine, the active constituent of chung chong (a traditional Chinese medicine). AB - Tetramethylpyrazine is extracted from Rhizoma ligustici wallichii, an herb used in the Chinese medicine Chung Chong. Both herb and extract have been used in the treatment of anginal pain and stroke. Animal studies in the West have shown that tetramethylpyrazine improves coronary blood flow, is short acting, and has a low toxicity. There are no clinical or animal studies on the uterine effects of tetramethylpyrazine. We present results of a preliminary study with isolated uterine strips from rats. We found that tetramethylpyrazine, in a dose-dependent manner (0.6 to 20 micrograms/ml), reduced uterine diastolic tone and inhibited the response to oxytocin (0.02 to 0.32 micrograms/ml). Higher concentrations of tetramethylpyrazine were needed to block the uterine responses to prostaglandin E2 (0.01 to 0.1 microgram/ml). On the basis of clinical and folk experience in the Far East, tetramethylpyrazine appears to have fewer systemic effects in human beings than have the beta-adrenergic agonists or calcium channel blockers. We suggest that studies in the whole animal and in the clinic might provide reasons to use tetramethylpyrazine to reduce uterine contractions and tone in pregnant women at term. PMID- 2589460 TI - Effect of magnesium on cocaine-induced, catecholamine-mediated platelet and vascular response in term pregnant ewes. AB - Ten pregnant ewes were alternated in a study of the blocking effect of parenteral magnesium on the catecholamine response to cocaine. Indirect blood pressures were recorded at 1-minute intervals for 12 minutes before and after a bolus of 2 mg/kg of cocaine. Fetal heart rates were continuously recorded from skin electrodes. Platelet counts were performed before and 12 minutes after cocaine. Control ewes received lactated Ringer's solution, and test animals had 5 mg/kg of elemental magnesium in the form of MgSO4-7H2O in a rapid infusion. A semicrossover was also performed. Platelet counts fell precipitately in controls and rose after magnesium infusions. Fetal heart rates rose in controls at 5-minute intervals and were unchanged in magnesium-treated mothers. Because of disparity of the baseline mean arterial pressure, direct comparisons were not significant before and after cocaine. Alterations from the baseline were different in magnesium-treated versus control animals, with values in the latter rising by 28 +/- 10 mm Hg with lactated Ringer's solution plus cocaine and falling by 3 +/- 5 mm Hg with magnesium pretreatment. Values in test animals originally treated with magnesium rose 4 +/- 11 mm Hg for an overall significance of p less than 0.05. Low beginning serum magnesium levels were associated with ovine hypertension and reduced fetal weight and survival. PMID- 2589462 TI - 5-Hydroxyeicosatetraenoic acid, leukotriene C4, and prostaglandin F2 alpha in amniotic fluid before and during term and preterm labor. AB - Arachidonic acid is metabolized by cyclooxygenase leading to prostaglandins and by lipoxygenases leading to hydroxyeicosatetraenoic acids (HETE) and leukotrienes (LT). Prostaglandins are potent uterine constrictors. 5-HETE and LTC4 also stimulate uterine contractions but their role in labor is not known. To estimate the activities of these pathways before parturition and their relationship to uterine contractility, amniotic fluid concentrations of 5-HETE, LTC4, and prostaglandin F2 alpha (PGF2 alpha) were determined in five chronically catheterized rhesus monkeys. Uterine contractility was continually assessed by recording changes in amniotic fluid pressure. The results obtained indicate the following conclusions: (1) 5-HETE and LTC4, but not PGF2 alpha, are associated with uterine contractility after preterm intrauterine surgery. Surprisingly, amniotic fluid PGF2 alpha, levels were nondetectable for 1 to 2 weeks after surgery. (2) 5-HETE and LTC4 are present in higher concentrations than PGF2 alpha in amniotic fluid. (3) 5-HETE, LTC4, and PGF2 alpha all increase with the onset of labor. Amniotic fluid concentrations of 5-HETE and LTC4 are significantly higher than those of PGF2 alpha before and during term and preterm labor. (4) Labor can occur with suppressed PGF2 alpha levels but with increasing 5-HETE and LTC4 levels. (5) These data suggest that 5-HETE and LTC4 are important components of the parturitional process. PMID- 2589461 TI - Effects of cephalic hypotension, hypertension, and barbiturates on fetal cerebral flood flow and metabolism. AB - The effect of altered perfusion pressure (cephalic arterial pressure minus sagittal venous pressure) on cerebral blood flow was examined in chronically catheterized fetal sheep under ganglionic blockade. Perfusion pressure was decreased by partial inflation of a brachiocephalic artery occluder and increased by an intravenous angiotensin II infusion. Cerebral flood flow was measured with radiolabeled microspheres. On average, 45% +/- 3% (SEM) reductions in perfusion pressure were accompanied by 49% +/- 4% decreases in cerebral blood flow. Increases in perfusion pressure of 42% +/- 3% were associated with 45% +/- 7% increments in cerebral flood flow. The cerebral oxygen consumption was not significantly altered in either case. We also investigated the effect of pentobarbital on fetal cerebral oxygen consumption and cerebral blood flow at normal and at altered perfusion pressure. At normal perfusion pressure pentobarbital caused a 27% +/- 5% decrease in cerebral oxygen consumption that was associated with a 44% +/- 4% decrement in cerebral blood flow and a slight widening of the arteriovenous oxygen content gradient. In this hypometabolic cerebral state, alterations in perfusion pressure were again accompanied by proportional changes in cerebral blood flow. Both perfusion pressure and the cerebral oxygen consumption appear to be important determinants of fetal cerebral blood flow. PMID- 2589464 TI - Ovine fetal cardiovascular responses to packed red blood cell transfusions. AB - Fifteen transfusions were performed in normal or anemic chronically catheterized sheep fetuses ranging in weight from 0.73 to 3.62 kg and in age from 91 to 135 days' gestation (term = 147 days). During the transfusions, an average of 29.0 +/ 2.5 (SE) ml/kg of packed maternal red blood cells (hematocrit = 78%) were given intravenously over 30 minutes and fetal hematocrit increased from 28.5% +/- 1.2% to 43.8% +/- 1.6%. Circulating blood volume increased by 13.9 +/- 2.3 ml/kg at 1 hour after transfusion and remained at this level at 24 hours. An average of 15.1 +/- 2.4 ml/kg of plasma was lost from the circulation at 1 hour after the transfusion. Fetal vascular pressures increased significantly during the transfusions and the rise in arterial pressure was greater than that in venous pressure (p less than 10(-6]. Heart rate decreased by 23 beats/min at the end of the transfusion and remained 13 beats/min below control after 1 hour (p less than 10(-6]. From the measured blood volume changes, formulas were developed so that the fetal blood volume before the transfusion and the posttransfusion hematocrit could be accurately calculated (r greater than 0.90). Thus this study shows that packed cell transfusions increase fetal blood volume by only 50% of the transfused volume because of a loss of plasma from the circulation and that the pretransfusion blood volume and the posttransfusion hematocrit can be accurately calculated from readily measured variables. PMID- 2589463 TI - Effects of systemic administration of indomethacin on ovulation, luteinization, and steroidogenesis in the rabbit ovary. AB - Indomethacin blocks ovulation in human chorionic gonadotropin-stimulated rabbits. Experiments were done with an in vitro ovarian perfusion system to investigate whether indomethacin affects luteinization and steroidogenesis. Indomethacin (10 mg/kg) was administered in combination with human chorionic gonadotropin (100 IU) via a marginal ear vein, and a second dose of indomethacin was given 8 hours later. Control animals received vehicle in place of indomethacin. Laparotomy was performed 24 hours after the initial treatment. The presence of unruptured follicles and corpora lutea was recorded and the ovaries were perfused in vitro for 3 hours. Progesterone, prostaglandin F2 alpha, prostaglandin E2, and 6-keto prostaglandin F1 alpha were measured in samples obtained at 0, 30, 60, 120, and 180 minutes from the circulating perfusion medium entering and exiting the ovary. At the end of the perfusion all ovaries (12 treated and 10 controls) were fixed for histologic analysis. Ovulation occurred in all control ovaries but in none of the indomethacin-treated ovaries. The mean number of unruptured follicles per ovary in the treated group was not significantly different from the number of corpora lutea plus unruptured follicles per ovary in the controls. Cells in both groups were qualitatively similar in ultrastructure; abundant lipid droplets, smooth endoplasmic reticulum, and mitochondria were seen. Secretion rates of progesterone and prostaglandin did not differ between the two groups during the 3 hour perfusion period. These results suggest that transformation of granulosa cells into fully functional luteal cells can occur in the absence of follicular rupture. PMID- 2589465 TI - The patient's reaction to side effects of oral contraceptives. AB - Approximately 14 million American women currently use oral contraceptives. This represents only 32% of those at risk for pregnancy. Many studies suggest that bleeding irregularities are a primary reason for discontinuation of oral contraceptives, especially among adolescents. The Triphasic Randomized Clinical Trial study and several others suggest that intermenstrual bleeding may be experienced by at least one third of women taking oral contraceptives at one time or another. The socioeconomic costs of these episodes, realized in calls and visits to physicians, as well as pill discontinuation, pregnancy, and perhaps abortion, carry their own unique set of risks. Absence of withdrawal bleeding, or amenorrhea, is another concern because, to the woman, it signals pregnancy. Roughly two thirds of patients who have amenorrhea while taking oral contraceptives will consult a physician. Physicians should select oral contraceptives with the lowest doses of hormones and fewest side effects such as breakthrough bleeding or amenorrhea, which are major obstacles to compliance. PMID- 2589466 TI - Uselessness of the phosphatidylglycerol assay for prediction of lung maturity. PMID- 2589467 TI - Haemophilus influenzae chorioamnionitis. PMID- 2589468 TI - Pregnancy in obstetrics residents. PMID- 2589469 TI - Semantic changes suggested in hypertensive disorders. PMID- 2589470 TI - Antepartum infection as a result of Streptococcus pneumoniae and sepsis in neonate. PMID- 2589471 TI - Double endometrial aspirative biopsy. PMID- 2589472 TI - Spatial patterns of human gene frequencies in Europe. AB - The aims of this study of spatial patterns of human gene frequencies in Europe are twofold. One is to present new methodology developed for the analysis of such data. The other is to report on the diversity of spatial patterns observed in Europe and their interpretation as evidence of population processes. Spatial variation in 59 allele and haplotype frequencies (26 genetic systems) for polymorphisms in blood antigens, enzymes, and proteins is analyzed for an aggregate of 3,384 localities, using homogeneity tests, one-dimensional and directional spatial correlograms, and SYMAP interpolated surfaces. The data matrices are reduced to reveal the principal patterns by clustering techniques. The findings of this study can be summarized as follows: 1) There is significant heterogeneity in allele frequencies among the localities for all but one genetic system. 2) There are significant spatial patterns for most allele frequencies. 3) There is a substantial minority of clinal patterns in these populations. Clinal trends are found more frequently in HLA alleles than for other variables. North south and northwest-southwest gradients predominate. 4) There is a strong decline in overall genetic similarity with geographic distance for most variables. 5) There are few, if any, appreciable correlations in pairs of allele frequencies over the continent, and there is little interesting correlation structure in the resulting correlation matrix. 6) Few spatial correlograms are markedly similar to each other, yet they form well-defined clusters. Spatial variation patterns, therefore, differ among allele frequencies. Patterns of human gene frequencies in modern Europe are diverse and complex. No single model suffices for interpretation of the observed genetic structure. Some clinal patterns reported here support the Neolithic demic-expansion hypothesis, others suggest latitudinal selection. Most of the clinal patterns are in HLA alleles, but there is also evidence from ABO for east-west migration diffusion. The majority of patterns are patchy, consistent with hypotheses of isolation by distance or of settlement of genetically differing, subsequently expanding ethnic groups. While undoubtedly there has been an ongoing stochastic process of differentiation consistent with the isolation-by-distance model, this has not obscured the directional patterns caused by migration (demic diffusion), and has perhaps only reinforced the contribution from settlement of ethnic units to patterns of genetic variation. However, the impact of the latter is most difficult to discern and requires further methodological developments. PMID- 2589473 TI - Blood genetic markers in the Chinese of two eastern provinces. AB - A total of 205 Han Chinese from two eastern provinces (155 from Fujien and 50 from Hopeh) were tested for the distribution of six blood groups--A1A2BO, MN, Rhesus (CcDEe), Lewisa, Kell (Kk) and Fya--four serum proteins--albumin and haptoglobin types; transferrin and group-specific component subtypes- haemoglobin, and twelve red cell enzyme systems--glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, lactate and malate dehydrogenases; acid phosphatase, esterate-D, glyoxalase I, adenylate kinase, glucose-phosphate isomerase, phosphoglucomutase (locus 2), and superoxide dismutase types; and phosphoglucomutase (locus 1) subtypes. The frequencies of blood groups were more or less within the reported frequencies in the Chinese. However the frequency of le was much lower in the present series. The Chinese are characterized by low p1, Ro, k, le, and a high Fya in general. P2 was lacking in the Chinese. There were some differences in the blood group frequencies in the two provinces. The frequencies of Hp alleles; Tf and Gc subtypes show characteristic mongoloid features with high Hp1, TfD, and GcIF. The frequency of TFC2 was higher in the Fujien province than that in Hopeh. At the hemoglobin locus only one Hb AD was detected, while the frequency of the beta-thalassemia trait was 0.03. No red cell G6PD deficiency or variant was detected. The distribution of red cell enzymes showed Mongoloid characteristics with low PGDC, AK2, ESD1, GLO1, and higher pa. PGM1 subtypes also had Mongoloid characteristics with lower PGM2+ and higher PGM2-. The phenotypic distribution of all the fifteen polymorphic loci was at Hardy-Weinberg equilibrium in both the Chinese populations. PMID- 2589474 TI - Nutritional determinants of high-altitude growth in Nunoa, Peru. AB - Data on nutritional intake and patterns of physical growth in the rural Andean community of Nunoa, Peru (elevation 4,000 m), are described and compared to data previously collected from this location. Food consumption data and selected anthropometric measures were obtained from a sample of 33 households. Estimates of caloric intake from this study are very similar to those obtained in Nunoa during the mid- and late 1960s. However, within the present sample, upper income (i.e., middle class) individuals have significantly higher caloric intakes than those of the lower income group and also appear to have an improved diet relative to individuals of 20 years ago. Anthropometric data show that children of the upper socioeconomic status (SES) group are significantly taller and heavier than the lower SES group children. Moreover, the children of the wealthier families are taller and heavier than the children measured 20 years ago at the same location, whereas the poorer children are not. These results indicate that nutritional factors have significantly contributed to the extreme pattern of slow growth previously reported for children of Nunoa and, moreover, demonstrate how social and environmental forces interact to create differential levels of stress that contribute to variation in biological well-being. PMID- 2589476 TI - Food transport through the anterior oral cavity in macaques. AB - Intraoral transport, the movement of food or liquid through the oral cavity and oropharynx, is a major component of feeding behavior. Stage I transport, transport through the oral cavity prior to mastication, has been described for several mammals (Franks et al.: Arch. Oral Biol. 30:539, 1985; Hiiemae and Crompton: Hildebrand et al. (eds.): Functional Vertebrate Morphology, Cambridge, MA, Belknap Press, 1985). Previous work (Franks et al.: Am. J. Phys. Anthropol. 65:275, 1984) indicated that this was not a significant behavior in macaques in a laboratory setting, because food was ingested directly to the region of the cheek teeth. Although relatively infrequent in a captive situation, stage I transport does occur in long-tailed macaques through a mechanism similar to other mammals, but also subject to unique aspects of primate anatomy. Transport takes several cycles during which the food moves back and forth in an anterior/posterior direction, due to tongue movements. Because anthropoid primates lack the pronounced rugae that in other mammals prevent the anterior displacement of a bolus, stage I transport uses the rounded arch of the upper, anterior dentition to hold the food during the forward movement of the tongue. During the final cycle of transport, a pronounced twisting of the tongue, along a midline anteroposterior axis helps funnel the food item toward the postcanine teeth for subsequent mastication. This twisting, which was described in humans by Abd-El Malek (J. Anat. 100:215, 1955) but not within the context of jaw movement, occurs prior to the closing phase of the jaw cycle. PMID- 2589475 TI - Allogrooming, partner choice, and dominance in male anubis baboons. AB - This study was designed to test the hypothesis that among unrelated male baboons (Papio cynocephalus anubis) in single-gender social groups there is no significant association between dominance status and allogrooming performance. The hypothesis was tested using behavioral measures obtained by focal animal sampling techniques. The results indicate that unrelated male baboons established well-defined linear dominance hierarchies, formed allogrooming relationships with one another, and exhibited a nonrandom distribution of allogrooming; however, there were no significant relationships between dominance rank and the frequency of allogrooming. We further tested our results by grouping individuals into three dominance status classes (high, middle, and low) and comparing the classes. Analysis of variance demonstrated no significant differences in rates of allogrooming by dominance class. These results suggest that dominance did not account for the variation in observed allogrooming behavior: Dominance status did not appear to determine the frequency with which animals groomed others, the number of grooming partners, or frequency of grooming that any individual received in comparison to that performed. High-ranking animals did not have significantly more grooming partners than low-ranking animals, and there appeared to be little competition within the groups for subordinates to groom high-ranking animals. When age, kinship, and group tenure are controlled, performance and reception of allogrooming are not strongly associated with dominance in single gender social groups of male anubis baboons. PMID- 2589477 TI - Sacral curvature and supine posture. AB - Sacral curvature (SC), represented by the angle between the first and the last sacral vertebrae, is a feature that differentiates the human pelvis from that of other animals. The sacral curvature was measured and studied in 14 cebids, 31 cercopithecids, 17 hylobatids, 85 pongids, 23 normal human children, 15 children with orthopedic handicaps, 49 normal adult human males, and 64 normal adult human females. Sacral curvature was minimal to nil in monkeys (mean 11.5 +/- 6 SD degrees), and moderate in apes (hylobatids, mean 16 +/- 10 SD degrees; pongids, mean 27.2 +/- 16 SD degrees). In human newborns SC is minimal, increasing progressively until adolescence, reaching a mean of 64.7 +/- 29 SD degrees in adult humans. This study investigates the different factors contributing to the formation of the sacral curvature. These factors include 1) the effect of erect posture, which tilts the upper part of the sacrum dorsally and the lower part of the sacrum ventrally, and 2) the influence of supine posture, which affects the development of the lower part of the sacrum. In addition to supine posture the levator ani, which is well developed in Homo sapiens, also affects the lower part of the sacrum and coccyx and influences its ventral orientation. Variation in SC can result from differences in onset and frequency of supine posture. This is the first time that supine posture has been shown to play a role in shaping the human pelvis, although it is as characteristic of H. sapiens as is erect posture. PMID- 2589478 TI - Acute and chronic responses of human renal kallikrein and kinins to dietary protein. AB - Glomerular filtration rate (GFR; creatinine clearance) and renal excretion rates of active kallikrein, prokallikrein, and kinins were measured in seven normal male subjects after a week on a constant low (40 g/day)-protein diet (LP) and during a subsequent week when only protein content was increased to 140 g/day (HP). Renal kinin excretion increased from 19.7 +/- 1.2 micrograms/day on day 7 of LP to 26.0 +/- 2.5 on day 1 of HP (P less than 0.002), and this higher rate persisted during HP. Active kallikrein excretion increased from 105 +/- 16 to 171 +/- 40 micrograms/day on day 2 of HP (P less than 0.006). Prokallikrein excretion did not increase significantly until day 4 of HP, 52 +/- 16 vs. 96 +/- 38 micrograms/day (P less than 0.03). The increases in active kallikrein and kinin excretion preceded an increase in GFR, which went from 117 +/- 6.8 ml/min on LP to 130 +/- 10 ml/min on day 5 of HP (P less than 0.003). At the end of the LP diet, acute ingestion of 40 g of a casein solution produced an increase in kinin excretion after 2 h (586 +/- 64 vs. 402 +/- 33 pg/min, P less than 0.001) and further to 640 +/- 74 pg/min at 3 h (P less than 0.001). This was accompanied by an increase in GFR at 3 h (154 +/- 18 vs. 132 +/- 10 ml/min, P less than 0.05). Kinin excretion rate correlated directly with GFR during both chronic (r = 0.87) and acute (r = 0.77) studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589479 TI - Effect of antidiuretic hormone on renal organic osmolytes in Brattleboro rats. AB - Homozygous Brattleboro rats were used to study the effect of antidiuretic hormone (ADH) on organic osmolytes, which have been shown to be involved in the cellular osmoadaptation in renal inner medulla. With the use of enzymatic spectrophotometric methods, glycerophosphorylcholine, sorbitol, and inositol were determined in kidney sections from papillary tip (IM3) to cortex. Compared with normal rat kidneys, IM3 of untreated Brattleboro rats (urine osmolality 132 mosmol/kg) were sorbitol depleted (16 +/- 1 vs. 371 +/- 37 mumol/g protein) and glycerophosphorylcholine was reduced to 20% (131 +/- 16 vs. 658 +/- 52 mumol/g protein). In contrast inositol was not changed (147 +/- 25 vs. 177 +/- 29 mumol/g protein). Similar effects were obtained in all medullary sections. Continuous treatment with ADH increased urine osmolality already after 5 h but renal glycerophosphorylcholine and sorbitol content only after 24 h. Normal osmolyte levels were reached after 3 days of ADH treatment when urine osmolality was 1,595 mosmol/kg. Inositol did not exhibit comparable changes during ADH treatment. The present results indicate that ADH, possibly by increasing interstitial tonicity, leads to increased glycerophosphorylcholine and sorbitol, but not inositol, contents. PMID- 2589480 TI - Calcium transport across rat inner medullary collecting duct perfused in vitro. AB - Ca2+ transport by the inner medullary collecting duct (IMCD) of normal rats was studied using the "in vitro" microperfusion technique. Net (Jnet), lumen-to-bath (Jl----b), and bath-to-lumen (Jb----l) fluxes of Ca2+ were measured in the absence of net water absorption using 45Ca as a tracer. In the absence of an electrochemical gradient, an important net absorption of Ca2+ (11.1 +/- 1.6 pmol.cm-2.s-1), similar to the difference between the Jl----b and Jb----l, was observed by direct determination at low (5-6 nl/min) and high (12-17 nl/min) perfusion rates. The Jl----b of Ca2+ was reduced by the addition to the bath fluid of ouabain (10(-3) M) and verapamil (10(-4) M), by the presence of amiloride (10(-5) and 10(-3) M) and verapamil (10(-4) M) in the luminal fluid, or by perfusion with a Na+-free solution. Neither the presence of verapamil (10(-4) M) and ouabain (10(-3) M) in the bath nor the withdrawal of Na+ from bath and perfusion solution was able to modify the Jb----l of Ca2+. Incrementing Ca2+ bath concentration increased proportionally the Jb----l of Ca2+. Therefore Ca2+ outflux is in part dependent on Na+-K+-adenosinetriphosphatase luminal membrane Na+ transport and in part inhibited by verapamil. However, Ca2+ influx is independent of Na+ transport, is not blocked by verapamil, but is increased by Ca2+ transtubular gradient, indicating the presence of a passive diffusion mechanism. PMID- 2589481 TI - Evidence for cholinergic innervation in dog renal tissue. AB - Denervation procedures that affect the sympathetic system of the kidney, as demonstrated by norepinephrine depletion of renal tissue, increased urine volume, fractional sodium excretion, and free water clearance in anesthetized water loaded dogs. These increases were reduced by atropine, which also blocked the increase above those basal functional levels produced by acetylcholine in both innervated and denervated kidneys. An in vitro tubular cell preparation of innervated kidneys corresponding to the outer cortex showed [3H]quinuclidinyl benzilate (QNB) binding parameters characteristic of muscarinic receptors. Denervation did not change either [3H]QNB binding parameters or the ability of inner and outer cortex cells to perform the hemicholinium-3-inhibitable, sodium dependent choline uptake and conversion of [3H]choline to [3H]acetylcholine. This cell membrane behavior is similar to that observed in tissues where cholinergic neuronal structures are present, suggesting the existence of a cholinergic innervation of the kidney, independent of the integrity of vessel-traveling nerves. Similarly, the finding of choline acetyltransferase in renal tissue, unaffected by sympathetic denervation, seems to confirm the presence of cholinergic nerve terminals. The cholinergic system may thus contribute to the regulation of tubular reabsorption of sodium and water in some conditions. PMID- 2589482 TI - Effect of acute renal decapsulation on pressure natriuresis in SHR and WKY rats. AB - The objective of these experiments was to study pressure natriuresis in the Wistar-Kyoto (WKY) and the spontaneously hypertensive rat (SHR) during acute bilateral renal decapsulation, a maneuver that partially blocks the increase in renal interstitial hydrostatic pressure (RIHP). In control WKY rats (n = 7), at renal perfusion pressure (RPP) of 105 +/- 0.7 and 125 +/- 1.1 mmHg, RIHP increased from 4.4 +/- 0.4 to 7.2 +/- 0.7 mmHg (P less than 0.05) and fractional excretion of sodium (FENa) increased from 0.23 +/- 0.05 to 1.32 +/- 0.14% (P less than 0.05). Acute bilateral renal decapsulation (n = 6) blunted the increase in RIHP observed when RPP was increased in control WKY rats and abolished the pressure natriuretic and diuretic response. When RPP was allowed to increase from 106 +/- 0.8 to 130 +/- 2.2 mmHg in the WKY rats with decapsulated kidneys, RIHP increased from 3.8 +/- 0.5 to 4.3 +/- 0.4 mmHg but FENa did not significantly change (0.31 +/- 0.12 to 0.43 +/- 0.13%). In control SHRs (n = 7), at RPPs of 135 +/- 0.8 and 163 +/- 3.0 mmHg, RIHP was 4.4 +/- 0.4 and 5.0 +/- 0.6 mmHg (NS) and FENa was 0.41 +/- 0.10 and 0.82 +/- 0.17% (P less than 0.05). Renal decapsulation in the SHR did not affect the blunted relationships between RPP, RIHP, and FENa; at RPPs of 135 +/- 0.3 and 162 +/- 2.9 mmHg (n = 7), RIHP was 4.4 +/- 0.6 and 4.7 +/- 0.5 mmHg (NS) and FENa was 0.43 +/- 0.10 and 0.95 +/- 0.22% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589483 TI - Essential fatty acid deficiency during acute puromycin nephrosis ameliorates late renal injury. AB - Puromycin aminonucleoside (PA) nephrosis is associated with a significant increase in the glomerular macrophage number during peak proteinuria. The significance of this observation remains uncertain. An essential fatty acid deficient (EFAD) diet depletes normal rat glomeruli of resident macrophages and alters glomerular eicosanoid metabolism. In this study, we found that an EFAD diet, administered only for the duration of the acute nephrotic phase, significantly ameliorated the recurrent albuminuria, renal dysfunction, and morphological injury characteristic of the late, recurrent phase of chronic aminonucleoside nephrosis. Glomerular macrophage number, isolated glomerular thromboxane B2 production, and circulating leukocyte and monocyte counts were significantly reduced in nephrotic rats on the EFAD diet 2 wk after PA injection, which temporally corresponds to peak albuminuria. The exact mechanism(s) by which the EFAD diet conferred protection in the late phase of chronic aminonucleoside nephrosis and lowered glomerular macrophage number during the acute nephrotic phase remain to be elucidated. PMID- 2589484 TI - Increased oxidative metabolism in renal tubules from spontaneously hypertensive rats. AB - Genetic hypertension in the rat is associated with abnormal renal function. This may be due to systemic hypertension or to intrinsic alterations in the kidney. Therefore, we examined intrinsic rates of oxidative metabolism in renal cortical tubules isolated from spontaneously hypertensive rats (SHR) and age-matched normotensive controls (WKY) before, during, and after the development of hypertension. We examined tubule function in SHR and WKY treated with antihypertensive agents to block the development of hypertension. During the early phase of hypertension (ages 7-8 wk), SHR tubules have intrinsic rates of oxygen consumption that are 15-25% greater than that of WKY. Ouabain-sensitive rates of oxygen consumption, an index of sodium entry, and Na+-K+-ATPase activity were not increased by 17%. Reduction of blood pressure with drugs did not abolish these differences in oxidative metabolism. Addition of exogenous arachidonic acid (1 microM) did reduce the metabolic differences between 8-wk-old SHR and WKY tubules. Norepinephrine (1 microM) had a greater stimulatory effect on oxygen consumption rates in tubules from hypertensive SHR. The relationship of these metabolic differences to the development of hypertension remains unclear. PMID- 2589485 TI - Cyclosporine augments renal mitochondrial function in vivo and reduces renal blood flow. AB - The in vivo action of cyclosporine A (CS) on rat renal cortical mitochondria was investigated. CS (30 mg.kg-1.day-1) given orally to rats for 30 days caused an augmentation of renal mitochondrial oxidative phosphorylation. The ADP-stimulated respiratory rate was increased by 37.0% with glutamate plus malate as respiratory substrates (P less than 0.025) but not with succinate-supported respiration, indicating enhancement of mitochondrial complex I activity. This reaction may be a response to the 32.5% reduction of renal blood (P less than 0.005) in the CS treated group, possibly serving to maximize ATP synthesis during ischemia. Ligation-induced decreases in renal blood flow also resulted in enhancement of mitochondrial complex I activity. PMID- 2589486 TI - Transport-coupling hypothesis of tubuloglomerular feedback signal transmission. AB - A mathematical model was used to explore the transport-coupling hypothesis of tubuloglomerular feedback (TGF) signal transmission from the macula densa (MD) to the extraglomerular mesangium (EGM) within the juxtaglomerular apparatus (JGA). The transport-coupling hypothesis supposes that changes in MD transport alter the ionic composition of the EGM interstitium, thereby stimulating the Goormaghtigh cells. This hypothesis is based on the avascularity of the EGM and the presence of a narrow cleft (JGA cleft) between the MD and Goormaghtigh cells. The model describes NaCl and water transport by MD cells and mass conservation in the JGA cleft. It calculates cleft water flow and NaCl concentration [( NaCl]). If the cleft is narrow, the model predicts that cleft [NaCl] will vary directly with luminal [NaCl] and net MD NaCl transport. With strong active NaCl transport, the MD cell plaque may act as an ionic amplifier, in that small changes in luminal [NaCl] might elicit much larger concentration changes within the cleft. Even without active NaCl transport, cleft [NaCl] could remain coupled to luminal [NaCl] if the MD cells passively secrete NaCl. With high hydraulic conductivity, cleft [NaCl] also varies with luminal osmolarity. With a wide cleft, a low diffusional resistance of the EGM interstitium, or swollen MD lateral intercellular spaces, the transport coupling between cleft and luminal [NaCl] is markedly attenuated. The predictions of our model of large changes in JGA interstitial composition agree well with published measurements made in Amphiuma. However, the low Na+-K+-ATPase content and high water permeability of mammalian MD suggest that the transport-coupling effects in mammals may be significantly less pronounced than in Amphiuma. PMID- 2589487 TI - Continuous-flow quantitation of Na+ and K+ in nanoliter samples using chromogenic macrocyclic ionophores. AB - Continuous-flow colorimetric methods for measurement of sodium and potassium contents in 1- to 30-nl aqueous samples are described. The methods employ macrocyclic ionophores (cryptahemispherands) that selectively bind sodium or potassium, altering the absorbance spectra of covalently attached chromophores. The potassium method is linear in the range 0-350 pmol and exhibits a high degree of precision (coefficient of variation of approximately 2% in the 150- to 350 pmol range). It can detect as little as 8 pmol of K+. The sodium method is linear in the range 0-2,700 pmol and also exhibits a high degree of precision (coefficient of variation of approximately 3% in the 1,700- to 2,700-pmol range). It can detect as little as 57 pmol of Na+. The instrumentation and reagents are available from commercial sources. These methods are proposed for measurement of K+ and Na+ fluxes in isolated perfused tubules. PMID- 2589488 TI - Effect of antidiuretic hormone on lithium as a marker for proximal tubule delivery. AB - To determine whether acute changes in antidiuretic hormone (ADH) alter the ability of lithium to quantitatively reflect proximal delivery, fractional lithium excretion (CLi/CIn) and late proximal (TF/P)In determined by micropuncture were measured in sodium-loaded rats following administration of desamino-8-D-arginine vasopressin (dDAVP) at rates equivalent to approximately half-maximal (20 pg/min) and maximal (40 pg/min) plasma levels of endogenous hormone. dDAVP dissociated the linear correlation between CLi/CIn and 1/(TF/P)In (r = 0.05) usually observed in sodium-loaded rats. Proximal delivery determined by lithium clearance underestimated (P less than 0.001) values obtained by micropuncture. Amiloride restored the linear correlation between CLi/CIn and 1/(TF/P)In in sodium-loaded dDAVP-treated rats (r = 0.70) and quantitative estimates of proximal delivery by each technique became equivalent. Indomethacin also reduced (P less than 0.001) estimates of proximal delivery obtained by lithium techniques in sodium-loaded rats. Water loading in hydropenic rats restored concordance between estimates of proximal delivery obtained by lithium clearance and micropuncture methods. Thus changes in ADH markedly alter the ability of lithium to function as a quantitative marker for proximal delivery. Furthermore, ADH may increase lithium uptake at distal nephron sites by an amiloride-sensitive pathway. PMID- 2589489 TI - Cardiac and peripheral vascular contributions to hypotension in spinal cats. AB - On transection of the cervical spinal cord, substantial decreases in systemic arterial pressure and in discharge of many sympathetic nerves suggest the absence of sympathetic support to the cardiovascular system. However, discharge of mesenteric and splenic nerves is well maintained in spinal cats (R. L. Meckler and L. C. Weaver. J. Physiol. Lond. 396: 139-153, 1988; R. D. Stein and L. C. Weaver. J. Physiol. Lond. 396: 155-172, 1988). We proposed that the low arterial pressure in spinal animals was caused predominantly by decreased cardiac output and vasodilation in muscle and some visceral vascular beds but that sustained mesenteric and splenic discharge was causing significant splanchnic vasoconstriction and partial support of arterial pressure. Therefore, changes in cardiac output, total peripheral resistance, and resistance of constant-flow perfused mesenteric visceral and hindlimb skeletal muscle vascular beds caused by interruption of cervical spinal pathways were assessed. Blockade of cervical pathways decreased arterial pressure as much by decreasing cardiac output as by decreasing total peripheral resistance. Resistances of the muscle and mesenteric vascular beds decreased equally. In conclusion, hypotension in spinal cats is caused by decreased cardiac output and by vasodilation, which is as prominent in mesenteric as it is in muscle vascular beds. The maintained mesenteric sympathetic discharge in spinal cats appears unable to produce significant support of vascular arterial resistance. PMID- 2589490 TI - Modulation of microvessel wall charge by plasma glycoprotein orosomucoid. AB - Haraldsson and Rippe suggested that the circulating glycoprotein orosomucoid (alpha 1-acid glycoprotein) contributes to the net charge on microvessel walls (Acta Physiol. Scand. 129: 127-135, 1987). We tested their hypothesis in individually perfused microvessels of frog mesentery by measuring solute permeability coefficients of two globular proteins (alpha-lactalbumin and ribonuclease) having approximately the same size (Stokes radius, 2 nm) but different charge (-11 and +3, respectively). In vessels perfused with orosomucoid (0.1 and 1 mg/ml) in a Ringer-albumin perfusate, the solute permeability coefficient of alpha-lactalbumin decreased to one-half [0.47 +/- 0.25 (SD)] the value in the absence of orosomucoid, and the solute permeability coefficient of ribonuclease was close to six times as large as alpha-lactalbumin permeability. Both results may be accounted for if orosomucoid increases the net negative charge on microvessel walls in frog mesentery from 11.2 to 28 meq/l. A similar change in microvessel charge would be more than sufficient to account for the decrease in albumin clearance in the presence of orosomucoid reported by Haraldsson and Rippe in rat muscle microvessels. PMID- 2589491 TI - Absent effect of plasma vasopressin on rat brain blood flow during hemorrhage. AB - We investigated whether a reflex increase in plasma vasopressin level due to hemorrhagic hypotension affects brain blood flow. In 60 lightly anesthetized, artificially ventilated rats, the flow was determined with radiolabeled microspheres. We found excellent maintenance of blood flow throughout all brain regions during the hypotensive state (71 mmHg on average), and such maintenance of flow was not modulated at all by a supramaximal intravenous dose of the selective vasopressin V1-receptor antagonist [d(CH2)5 Tyr-(Me)]AVP. The latter finding also implies that the V1 antagonist failed to unmask the vasodilator type actions of V2 receptors on the maintenance of flow during hemorrhagic hypotension. These were true also when the cervical sympathetic bundles were severed bilaterally. The plasma level of endogenous vasopressin was increased during hypotension, ranging from 118 to 973 pg/ml. Despite this increase, the brain blood flow was entirely independent of the plasma vasopressin level in all the brain regions studied. We conclude that the brain circulation of rats can maintain its blood flow during hemorrhagic hypotension without any apparent contribution from a concomitant reflex increase in plasma vasopressin. Despite our negative results for the brain blood flow, the possible segmental effects of circulating vasopressin on the brain arterial caliber remain to be clarified under conditions of hemorrhagic hypotension. PMID- 2589492 TI - Rapid cooling contractures as an index of sarcoplasmic reticulum calcium content in rabbit ventricular myocytes. AB - Rapid cooling contractures (RCCs) were used to assess changes in sarcoplasmic reticulum (SR) Ca content in both isolated rabbit ventricular myocytes and multicellular preparations. The main difference observed between these preparations was the magnitude of RCCs relative to twitches, apparently due to differences in measured parameters, i.e., unloaded shortening vs. isometric tension. When multicellular preparations were unloaded, RCC shortening was similar to that observed in myocytes. RCC magnitude decreased as the time between the last electrical stimulation and the RCC was increased (rest decay). RCC rest decay closely paralleled that of postrest twitches, suggesting that SR Ca loss is responsible for this process. Paired RCC experiments were used to investigate RCC relaxation and rest decay. When a second RCC (RCC2) was induced immediately after the first (RCC1), a large contracture was still observed (RCC2/RCC1 x 100 = 77.8 +/- 7.3%, mean +/- SD), indicating that the SR resequestered the majority of Ca on rewarming. This fraction was increased (to 92.9 +/- 5.5%) if Na and Ca-free solution was used during RCCs and rewarming, indicating that Na-Ca exchange also contributes to RCC relaxation. Increasing the interval between paired RCCs led to a decrease in RCC2, analogous to rest decay. This rest decay was abolished by inhibiting Na-Ca exchange, indicating that SR Ca loss during rest is mediated primarily by this process. RCCs were abolished by 10 mM caffeine. Ryanodine (1 microM) greatly accelerated RCC rest decay but had less effect on RCCs generated immediately after a train of stimulation. This accelerated rest decay was also dependent on Na-Ca exchange.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589493 TI - Role of adenosine in hypoxic alterations of anaphylaxis of isolated guinea pig hearts. AB - Previous studies suggest that high levels of adenosine may enhance histamine release and contribute to atrioventricular (AV) nodal conduction arrhythmias during anaphylaxis of isolated guinea pig hearts. To determine whether elevations in endogenous adenosine evoked by hypoxic conditions have similar effects, isolated hearts of guinea pigs passively sensitized by intracardiac injection were perfused with solutions equilibrated with 95% O2 (normoxia) or 30% O2 (hypoxia). When compared with normoxia, hypoxia before antigen challenge increased adenosine release, decreased vascular resistance, and prolonged P-R intervals, whereas hypoxia during anaphylaxis potentiated the increase in adenosine release, attenuated the increases in vascular resistance and atrial rate, and increased the occurrence of conduction arrhythmias without altering the antigen-induced release of either histamine or thromboxane. Addition of the adenosine receptor antagonist 8-(4-sulfophenyl)theophylline (SP-T) to the hypoxic perfusate significantly decreased antigen-induced release of histamine and thromboxane. These data indicate that 1) hypoxia-induced depression of antigen induced mediator release may be counteracted by the stimulatory effect of the increased adenosine induced by hypoxia, and 2) under hypoxic conditions, adenosine's negative dromotropic, chronotropic, and vasodilatory effects may influence the anaphylactic reaction. PMID- 2589494 TI - Reductions in central venous pressure improve carotid baroreflex responses in conscious men. AB - To test the hypothesis that unloading cardiopulmonary receptors improves human carotid baroreceptor responsiveness we measured heart rate (HR) and mean radial artery blood pressure (BP) responses elicited by trains of neck pressure and neck suction from +40 to -65 Torr during graded lower body negative pressure (LBNP) at -5, -10, -15, -20, -35, and -50 Torr in eight healthy men. Gain of the carotid baroreflexes was determined from logistic modeling of the HR [expressed as R-R interval (RRI)] and BP responses to neck pressure and neck suction. Central venous pressure (CVP) decreased progressively from control values of 6.2 +/- 0.6 (SE) Torr to -0.8 +/- 0.1 Torr at -50 Torr LBNP (P less than 0.001). HR changed little from control values of 62.7 +/- 2.1 beat/min to 65.9 +/- 2.8 beat/min at 15 Torr (P = NS), but increased significantly to 80.6 +/- 2.6 beats/min at -50 Torr (P less than 0.001). Maximum gain of the HR and BP stimulus-response curves was linearly and inversely related to decreases in CVP and could be described by the relationships Max RRI gain = -0.694 (CVP) + 11.6 [r2 = 0.94, standard error of estimate (SEE) = 0.45, P less than 0.001] and Max BP gain = -0.0292 (CVP) + 0.391 (r2 = 0.81, SEE = 0.038, P less than 0.001). We suggest that reductions in central venous pressure and/or central blood volume augment both HR and BP carotid baroreflex responses in man by reducing an inhibitory influence from cardiopulmonary receptors. PMID- 2589495 TI - Maternal environment and development of high blood pressure in Dahl hypertensive rats. AB - The contribution of the preweanling maternal environment to the development of hypertension was examined using the technique of reciprocal cross-fostering between two inbred rat strains, the Dahl hypertension-sensitive (SS/Jr) rat and the Dahl hypertension-resistant (SR/Jr) rat. Litters of SS/Jr and SR/Jr pups were reared by their natural mother, in-fostered to a dam of the same strain, or cross fostered to a dam of the opposite strain for the entire preweanling period from postnatal days 1 to 30. At 60 and 100 days of age, one rat from each litter was surgically prepared with an indwelling catheter in the ventral tail artery. One day after surgery, measures of resting mean arterial pressure and heart rate were taken as the animals were resting and undisturbed in their home cages. Body weights were also obtained at 30, 60, and 100 days of age as a measure of general somatic development. Our findings indicate that SS/Jr rats fostered to SR/Jr dams exhibited a significant reduction in resting mean arterial pressure compared with naturally reared or in-fostered SS/Jr rats (P less than 0.01 at 60 days and P less than 0.03 at 100 days). Conversely, arterial pressure of SR/Jr rats did not differ across rearing conditions at either age. Body weights were not significantly affected by cross-fostering in either strain. We conclude from these results that characteristics of the SS/Jr maternal environment interact with the inbred genetic susceptibility of the SS/Jr pup to elicit the full expression of the SS/Jr hypertensive phenotype. PMID- 2589497 TI - Chemodenervation does not alter cerebrovascular response to hypoxic hypoxia. AB - We tested the hypothesis that sinoaortic chemodenervation would alter the increase in cerebral blood flow (CBF) during isocapnic hypoxic hypoxia in 1- to 7 day-old lambs. Lambs were anesthetized with pentobarbital and studied during moderate (arterial O2 content [CaO2] = 10 vol/100 ml) and severe (CaO2 = 6 vol/100 ml) hypoxic hypoxia. Regional brain blood flows were measured with the radioactive microsphere technique. Cerebral oxygen consumption (CMRO2) was calculated as the product of forebrain blood flow and the difference in oxygen contents between arterial and sagittal sinus blood. Lambs were then subjected to either sham surgery (n = 6) or to carotid chemodenervation and cervical vagotomy (n = 6). Chemodenervation was verified by abolition of the transient increase in blood pressure after intravenous injection of sodium cyanide in intact subjects. Neither sham surgery nor chemodenervation had an effect on CMRO2 or CBF during hypoxic hypoxia. These data thus do not support the hypothesis that arterial chemoreceptors play any substantial role in the regulation of cerebral vascular tone during hypoxic hypoxia in the 1- to 7-day-old anesthetized lamb. PMID- 2589496 TI - Hemodynamics and blood volume in angiotensin II salt-dependent hypertension in dogs. AB - The sequential effects of an increased daily NaCl intake on hemodynamics, fluid electrolyte balances, and hormonal responses were evaluated in dogs (n = 7) with fixed circulating levels of angiotensin II (ANG II). During the control period, ANG II was infused at 3 ng.kg-1.min-1 while dogs were maintained on an 8 meq NaCl/day diet. Water intake was fixed at 700 ml/day. Continuously recorded (24 h/day) changes of total body weight (TBW) were used as an index of total body water. Cardiac stroke volume and arterial pressure were recorded, and each beat was digitized to provide hourly and 24-h average cardiac output (CO), mean arterial pressure (MAP), and total peripheral resistance (TPR). After three stable control days, daily salt intake was increased to 120 meq for 7 days. TBW increased gradually to 448 +/- 111 g (2.9%, P less than 0.05) above control by day 3. An 11% expansion of blood volume (P less than 0.05) was found (51CR labeled red blood cells) on day 2 of high NaCl. CO rose 12% and MAP 20% (P less than 0.05) in parallel with TBW by day 4. By day 7, CO remained only 5% elevated, whereas MAP had stabilized at 20% above control levels. TPR remained significantly elevated from days 3 through 7. A positive Na balance averaging 91 +/- 8 meq (P less than 0.05) occurred on day 1. Plasma Na concentration was increased 2-3 meq/l above control throughout the period of high-salt intake. Plasma renin activity and aldosterone levels decreased to nearly undetectable levels, vasopressin rose slightly, and atrial natriuretic peptide levels increased significantly. Dogs maintained at 8 meq/day NaCl during the same infusion of ANG II showed no changes in MAP, CO, TPR, or TBW. In summary, the salt-induced hypertension was consistently related to small but significant fluid retention, blood volume expansion, elevations of cardiac output, and a gradual increase in TPR. PMID- 2589498 TI - Hemodynamics at low flow in resting vasodilated rat skeletal muscle. AB - The low flow arterial pressure-flow relationship and zero-flow pressure (ZFP) are investigated in the hemodynamically isolated gracilis muscle using a high precision pump. The muscle is kept in situ with dilated vasculature. During steady-state perfusion, using a plasma-like medium, the pressure-flow curve is nonlinear with positive arterial ZFP of 3.5-12 mm Hg when normal central circulation pressure is present. When the central circulation is stopped the ZFP reduces to zero. Addition of nonaggregated red blood cells (RBCs) results in no significant increase in the ZFP; however, introduction of aggregated RBCs (with dextran, 77 kDa) causes a 9.4 +/- 1.2 mmHg elevation. The positive ZFPs observed using plasma-like and dispersed RBC perfusions are found to be caused by a back pressure from the central circulation via collateral arterioles. A single-step reduction of the arterial flow rate from a finite value to zero results in a ZFP, which decreases for more than a minute before steady state is reached. During harmonic flow inputs with oscillations down to zero flow, an increase in the ZFP is detected near 0.09 Hz and continues to rise up to the test limit of 10 Hz. Our results suggests that in vasodilated skeletal muscle three independent mechanisms exist, collateral flow, cell aggregation, and unsteady perfusion, which may cause a positive arterial ZFP. PMID- 2589499 TI - Dynamic exercise in senescent beagles: oxygen consumption and hemodynamic responses. AB - Seven senescent beagles and seven younger mature beagles were studied at rest, as well as during maximal and submaximal exercise on a motor-driven treadmill. Maximal exercise capacity was significantly (P less than 0.05) reduced, and maximal total body O2 consumption (VO2 max) was 31% lower in senescent beagles. VO2 was also significantly reduced in old dogs, when directly compared at the same relative workloads in old and younger mature dogs. However, VO2 was very similar in both groups during each of the absolute levels of directly comparable exercise. The observed age-related reduction in VO2 max was associated with a significant 25% reduction in maximal cardiac output (CO) in senescent beagles, and with an 11% reduction in maximal arteriovenous O2 difference. CO was also significantly reduced in old dogs at the same relative levels of submaximal exercise evaluated. Combined effects of reductions in stroke volume and in heart rate both contributed to the observed reductions in CO observed in senescent dogs during maximal exercise, as well as during relative levels of submaximal exercise. However, CO responses at each absolute level of submaximal exercise were similar in senescent and younger mature beagles, and the relationship between CO and VO2 was also similar in both groups. Increases in stroke volume significantly contributed to observed increases in CO beginning at the same relative level of exercise in both old and young dogs. Results of this study demonstrate that significant age-related changes in VO2max and in other associated hemodynamic parameters occur during maximal exercise. Many of these changes are also apparent when relative levels of submaximal exercise are directly compared in senescent and in younger mature beagles. However, most hemodynamic responses during absolute levels of exercise are similar in both groups, unless these parameters reflect the relative workload performed, indicating that these responses are appropriate for each absolute level of work that can be performed in the senescent dogs. PMID- 2589500 TI - Structure of canine Bachmann's bundle related to propagation of excitation. AB - Impulse propagation and histology were studied in adult and neonatal canine Bachmann's bundle. Both showed nonuniform electrical anisotropy: effective longitudinal conduction velocity (theta L) markedly exceeded effective transverse conduction velocity (theta T), and extracellular potential waveforms with transverse propagation were polyphasic. An age difference in theta L (0.80 m/s neonate, 1.31 m/s adult) was found; it could be largely accounted for by a difference in myocyte diameter (4.7 microns neonate, 17.1 microns adult). Close apposition of myocytes in the neonate and development of transverse tubules in the adult may have influenced theta L at each stage. Perimysial septa separated fascicles in both neonatal and adult bundles; however, endomysial septa between individual myocytes were completely developed only in adult bundles. Thus perimysial septa were much more responsible for nonuniform anisotropy and low theta T than endomysial septa. Fascicle diameter and length were greater in the adult, which may have affected transverse propagation. Specialized conduction system cells could not be identified. PMID- 2589501 TI - Effect of lysophosphatidylcholine on the filtration coefficient in intact dog lungs. AB - Lysophosphatidylcholine (lyso-Pc) is a lysophospholipid normally found in low concentrations in the lung. At high concentrations lyso-Pc, instilled into the airways, causes pulmonary edema. We tested the hypothesis that the edema caused by lyso-Pc was due to an increase in pulmonary microvascular membrane permeability. In 11 anesthetized dogs we continuously weighed the left lower lobes (LLL) while instilling lyso-Pc (20 mM) into the LLL airways. After 30 min we determined the microvascular membrane fluid filtration coefficient (Kf) from the relationship between the rate of LLL weight gain and the pulmonary microvascular pressure. Kf was not significantly different between the lyso-Pc treated lobes (0.048 +/- 0.018 ml.min-1.mmHg-1) vs. control lobes (0.067 +/- 0.031 ml.min-1.mmHg-1). Our data do not support the hypothesis that lyso-Pc, instilled into the airways, causes an increase in pulmonary microvascular permeability. PMID- 2589502 TI - Varying elastance concept may explain coronary systolic flow impediment. AB - We measured phasic arterial coronary inflow in the blood-perfused isolated cat heart (n = 5) with a balloon in the left ventricle under well-defined conditions, i.e., constant perfusion pressure, constant vasomotor tone (maximal vasodilation), and heart rate. The normalized amplitude (A) between systolic flow (Fs) and diastolic flow (Fd) [A = (Fd - Fs)/Fd] was related to systolic left ventricular pressure (Ps, range 1.6-17 kPa, 1 kPa = 7.5 mmHg) for different isovolumic beats obtained by changes in balloon volume and for low load isobarically ejecting beats (pressure 0.2 kPa). The data were fitted to A = a + bPs with a = 0.70 +/- 0.15 (SD) and b = 0.005 +/- 0.005 kPa-1. This relation indicates a very weak effect of left ventricular systolic pressure on normalized flow amplitude. Thus the hypothesis that left ventricular pressure is the sole determinant impeding coronary flow could not be confirmed. However, our data could be explained on basis of the time-varying elastance concept (H. Suga, K. Sagawa, and A. A. Shoukas. Circ. Res. 32: 314-322, 1973). The intravascular and luminal (cavity) compartments both are assumed to be subject to a time-varying elastance. The time-varying luminal elastance is similar for isovolumic and isobaric beats. We assume that the elastance of the vascular compartment also behaves the same for these beats, and therefore coronary flow is affected similarly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589503 TI - Acute aortic coarctation hypertension: role of vasopressin and angiotensin II. AB - The role of vasopressin (AVP) and angiotensin II (ANG II) in the onset of acute (45 min) aortic coarctation hypertension was studied in conscious rats. Changes in mean carotid pressure (MCP) and heart rate (HR) were measured in four groups of rats. Control rats presented a hypertensive response that attained a plateau 5 min after coarctation and remained near this level throughout the experiment. Rats treated with AVP V1-vascular receptor antagonist [1-(beta-mercapto-beta,beta cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine]arginine vasopressin [d(CH2)5Tyr(Me)AVP] presented a prompt rise in MCP similar to the control rats, but in contrast to this group, the MCP started to decline progressively. Rats treated with saralasin presented a delay in the onset of hypertension right after coarctation but slowly attained values similar to those for control rats. In contrast, the rats treated with AVP antagonist plus saralasin showed a blunted MCP elevation throughout the experiment. Reflex bradycardia observed in the rats treated with saralasin or the AVP antagonist plus saralasin was similar to that observed in the control rats, whereas for the group treated only with AVP antagonist, the reflex bradycardia was more intense than for the other three groups, indicating an increased sensitivity of the baroreflex. These data demonstrate that in addition to the mechanical effect of aortic constriction, both ANG II and AVP participate in the onset of acute aortic coarctation hypertension. Moreover, the results indicate that ANG II acts on the prompt (5 min) rise in pressure, whereas AVP is responsible for the maintenance (30-45 min) of the arterial pressure elevation. PMID- 2589504 TI - Effects of endothelial impairment on arteriolar dilator responses in vivo. AB - In pentobarbital-anesthetized rats we investigated the role of the endothelium in the dilation of third-order arterioles of cremaster muscle to acetylcholine, adenosine, and sodium nitroprusside in vivo. Responses to the topical administration of these agents were measured with image shearing and recorded with video microscopy before and after light-dye (L-D) treatment of a 50- to 100 microns segment of the arteriole under study. L-D treatment consisted of intravascular administration of sodium fluorescein and the illumination of a discrete area of the arteriole under study with its excitation light from a mercury lamp. Before L-D treatment, acetylcholine (10(-7) to 10(-5) M) and adenosine (10(-6) to 10(-4) M) produced dose-dependent increases in arteriolar diameter (vasodilation). After L-D treatment of the arteriolar segment, administration of 10(-7) M acetylcholine evoked a vasoconstriction (-19% from control), and the dilator responses to 10(-6) and 10(-5) M were inhibited by 91 and 77%, respectively. In contrast, the arteriolar dilator responses to all doses of adenosine and sodium nitroprusside (2 x 10(-7) M) were not altered by this treatment. In addition, the dilator responses to acetylcholine were not changed in the nonilluminated, distal, and proximal segments of the arterioles. These findings suggest that L-D treatment selectively alters the function of the endothelium resulting in the loss of vasodilation to acetylcholine, whereas arteriolar smooth muscle function does not appear to be affected. PMID- 2589505 TI - Determinants of force decline during relaxation in isolated cardiac muscle. AB - Determinants of the time course of isometric force decline are less well known than those of peak rate of force decline. We studied the influence of loading history, nonuniformity, extracellular calcium, and muscle length on force decline in isolated right ventricular cat papillary muscle. Changes in contraction load affected the time of onset but not time course of force decline at any given length and contractile state. Despite delayed time of onset of force decline (up to 80% of time to peak twitch), rate of force decline was identical at equal force levels. No direct influence of nonuniform behavior of longitudinal segments on the pattern of muscle force decline was observed. The rate of terminal force decline (toward the end of relaxation) was not influenced by extracellular calcium but significantly increased at short muscle lengths: its time constant (means +/- SE) averaged 85 +/- 12 ms at optimal length and decreased by 20 +/- 6 ms per 10% reduction in length. Force control of rate of force decline and its modulation by length can be understood by considering the influence of force and length on sensitivity of contractile proteins to calcium. PMID- 2589506 TI - Peripheral baroreceptor control of neurohypophysial blood flow during hemorrhage. AB - We measured neurohypophysial blood flow (NHBF) in dogs made hypotensive to study the time course of neurohypophysial autoregulation. We found that the neurohypophysis has a unique autoregulatory response in which blood flow increases transiently before establishing a stable perfusion level. During the "hyperemic" phase, the time course of the flow transient correlates with an increased plasma arginine vasopressin (pAVP) neurosecretory transient. However, unlike pAVP, blood flow does not remain elevated. The transitory nature of the flow response led us to evaluate the hypothesis that peripheral baroreceptor activity may be responsible for the hyperemic phase. Bilateral vagotomy and carotid sinus nerve denervation attenuated the increase in neural lobe blood flow (NLBF) to a standardized step to 80 mmHg mean arterial pressure. The pAVP response was enhanced both by vagotomy and carotid sinus denervation. Combined denervation abolished both the pAVP and the NLBF responses. We conclude that NHBF is autoregulated; however, control may be exerted at multiple levels, i.e., via nerves as well as local metabolic mechanisms. The peripheral baroreceptors influence NHBF primarily during periods of changing blood pressure. When blood pressure is stable, local mechanisms appear to be dominant. PMID- 2589507 TI - Effects of dipyridamole on muscle blood flow in exercising miniature swine. AB - The purpose of this study was to determine whether a vasodilator reserve exists in respiratory muscles and forelimb skeletal muscles in miniature swine during treadmill exercise. Blood flow (BF) was measured with radiolabeled microspheres during preexercise and before and after dipyridamole (DYP; 1 mg/kg iv) at 2 min of treadmill exercise at 11.2 (70% Vo2 max) and 17.6 km/h (Vo2 max). Muscle BFs were increased during exercise, and the relationship between exercise intensity and BF varied among the muscles. The high-oxidative extensor muscles and the flexor muscles attained peak BFs at 11.2 km/h, whereas the more superficial, lower oxidative extensor muscles showed increases in BF up to maximal exercise. During running at 11.2 km/h, DYP produced increases in BF only in cardiac muscle, respiratory muscle and the medial head of the triceps muscle (MHT), which is composed of 91% slow-twitch oxidative (SO) fibers. During maximal exercise (17.6 km/h), DYP produced a 31-mmHg decrease in mean arterial pressure (MAP) and increases in vascular conductance in all muscles studied. BF was only increased in MHT and cardiac muscle. We conclude that vasodilator reserve remains in skeletal muscle and respiratory muscle even during maximal exercise in swine. If it is assumed that DYP-induced vasodilation in a muscle sample is indicative of adenosine production, these results suggest that SO skeletal muscle (MHT) and respiratory muscle are similar to cardiac muscle in that they produce adenosine even when adequately perfused. Furthermore, during maximal exercise, all skeletal muscle appears to produce adenosine, suggesting that muscle BF is restricted under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589508 TI - Effect of voltage and charge of electrical ablation pulses on canine myocardium. AB - Multiple paired lesions produced by a train of high-voltage low-charge rectangular pulses (20 A, 30 microsecond) and a train of low-voltage high-charge rectangular pulses (2 A, 300 microsecond) were made to the left ventricular epicardium of 23 dogs to determine the relative influence of voltage and charge delivery on injury of canine myocardium. Both pulsing methods contained equal amounts of energy (15 J) delivered over equal periods of time (100 ms), and both pulsing methods were nonarcing and therefore nonbarotraumatic. The volume of cardiac tissue injury resulting from both types of pulses was then evaluated from planimetered serial histological sections after 1, 10, and 30 days. Over the 30 day period, lesion size progressively decreased to 56% of its original value for the high-voltage low-charge pulse. In contrast, lesion size from the low-voltage high-charge pulse remained relatively constant, decreasing only 12% of its original value. These results indicate that when energy delivery is held constant, voltage, not charge, is the dominant mediator of cell injury. Also, cells subjected to high voltages appear to recover partially over time with significantly less constancy of tissue injury than that seen with low-voltage high-charge pulses. PMID- 2589509 TI - Effects of intracardiac bradykinin and capsaicin on spinal and spinoreticular neurons. AB - The responses of thoracic spinal and spinoreticular tract (SRT) neurons to activation of cardiac spinal afferents by injections of bradykinin (BK) and capsaicin (CAP) into the left atrium or pericardial sac were determined in vagotomized cats anesthetized with alpha-chloralose. Activities of spinal and SRT neurons in the T1-T5 spinal cord were recorded extracellularly. All neurons received excitatory somatic and cardiopulmonary sympathetic afferent input. Application of BK and CAP to the heart excited most SRT neurons and many spinal neurons but also inhibited some spinal neurons. The two drugs often affected spinal but not SRT neurons differently. Capsaicin excited high threshold and high threshold inhibitory neurons but not wide-dynamic range spinal neurons. In contrast, BK excited all three categories of spinal and SRT neurons. The differential responses of spinal neurons to intracardiac BK and CAP suggested that these compounds can stimulate functionally different populations of cardiac sympathetic afferents. PMID- 2589510 TI - Effects of activation of ATP-sensitive K+ channels in mammalian ventricular myocytes. AB - A cromakalim analogue, SR 44866, is shown to open ATP-sensitive K+ channels in ventricular myocytes. The channels opened by SR 44866 were closed by internal ATP and had the same current-voltage relationship as ATP-sensitive K+ channels; channels closed by ATP could be opened by SR 44866. SR 44866 was effective when applied to either side of excised membrane patches and when included in the pipette during cell-attached membrane recordings. SR 44866 also opened channels in cell-attached membrane patches when it was applied to the cell membrane outside of the pipette. The current evoked by SR 44866 in whole cell recordings was inhibited by tolbutamide. SR 44866 reduced the duration of action potentials and the amplitude and duration of evoked muscle contractions in guinea pig papillary muscle, with dissociation constants of 6.8 microM at 24 degrees C and 1.9 microM at 34 degrees C and Hill coefficients of 1.72 and 1.71, respectively. We conclude that the opening of ATP-sensitive K+ channels has profound inhibitory effects on the electrical and mechanical activity of cardiac muscle. PMID- 2589511 TI - Stimulus-specific changes in mechanical properties of vascular smooth muscle. AB - To determine whether the mechanical properties of vascular smooth muscle are stimulus specific, force, stiffness, and the unloaded shortening velocity (Vmax) were measured during contractions of aortic smooth muscle strips stimulated with phenylephrine or KCl. After activation, muscle force and stiffness rose to a steady-state plateau where they were maintained. In phenylephrine contractions, Vmax peaked during force development and then fell to a lower steady-state level during force maintenance, whereas in the KCl contractions, Vmax did not decline during sustained contractions. Stimulation with KCl, compared with phenylephrine, produced lower steady-state forces. One possible interpretation is that the muscle formed latch cross-bridges during phenylephrine contractions, but not during KCl depolarizations. The slope of the plot of relative muscle force vs. stiffness for phenylephrine contractions, compared with KCl depolarizations, was reduced. This may imply tht the relative force per attached latch crossbridge could be reduced. PMID- 2589512 TI - Neural regulation of canine skeletal muscle blood flow during hypoxic hypoxia. AB - Vascular resistance in canine limb skeletal muscle first increases and then decreases with prolonged arterial hypoxia, but whether neural sympathetic activity decreases with time is unknown. To assess the effectiveness of neurally mediated vasoconstrictor tone, we periodically cooled and rewarmed the sciatic nerve while nine anesthetized, paralyzed, pump-ventilated dogs were made hypoxic for 60 min by ventilation with 9.1% O2 in N2 (PaO2 = 24 +/- 2 mmHg). Before hypoxia, limb blood flow (QL) increased to a mean peak value of 111 ml.kg-1.min-1 with nerve cooling. With hypoxic hypoxia (HH), cardiac output increased but mean arterial pressure and limb blood flow remained the same. Nerve cooling at 15, 30, and 60 min of HH resulted in a pattern of progressively increasing mean peak QL values of 137, 151, and 160 ml.kg-1.min-1, respectively (P less than 0.05). Stimulation of the cut sciatic nerve at the end of the experiment established the maximum vasoconstriction that was possible and, thereby, the potential range that was available. The results showed that not only was neurally mediated vasoconstriction to skeletal muscle maintained throughout the hypoxic period, but that its intensity must have been increasing to overcome the local vasodilatory forces that were responsible for flow increasing even further with nerve cooling in prolonged hypoxia. PMID- 2589513 TI - Membrane cytochemistry of the atrial peptide secretory pathway. AB - The characteristics of the principal membrane systems involved in atrial peptide secretion are explored in rabbit and rat atrial muscle cells using freeze fracture electron microscopy combined with cytochemistry. Structural features of the Golgi apparatus and secretory granule membrane are described, and two features of the membranes' composition, cholesterol content and terminal glycocomponents, are probed in situ in the cell. Both the secretory granule membrane and the plasma membrane contain morphologically detectable cholesterol, and both are rich in the terminal sugar residues (sialic acid and N-acetyl glucosamine) of membrane glycocomponents. Some cisternal membranes of the Golgi apparatus reveal detectable cholesterol but others do not, and only focal labeling of terminal glycocomponents in Golgi membranes is observed, usually adjacent to the accumulation of secretory product. Nuclear membranes, endoplasmic reticulum, and mitochondria contain virtually no detectable cholesterol nor terminally glycosylated components. The Golgi apparatus, which is exclusively equipped with the enzymes responsible for terminal glycosylation of membrane glycoproteins, appears actively to modify the chemical composition of the membrane segments in which it packages atrial peptide. This ensures that the composition of the atrial granule membrane resembles that of the plasma membrane into which it is ultimately incorporated. PMID- 2589514 TI - Selective abolition of adrenergic vasoconstrictor responses in skin by local iontophoresis of bretylium. AB - Skin blood flow (SkBF) in humans is controlled by a noradrenergic active vasoconstrictor system and an active vasodilator system of an uncertain neurotransmitter. Understanding how these systems interact would be aided if the vasodilator system could be studied in the absence of effects of the vasoconstrictor system. To accomplish this we combined laser-Doppler velocimetry (LDV) with the local iontophoresis of bretylium in 10 studies with eight healthy subjects. Each subject had two forearm sites (0.64 cm2) treated with bretylium to block local norepinephrine release. LDV was monitored at those sites and at two untreated sites during 3-4 min of cold stress, 35-45 min of heat stress, and a final cold stress to verify blockade. In five studies, local temperature was raised to 39 degrees C at the LDV sites before the final cold stress. Whole body skin temperature was controlled by water-perfused suits. Mean arterial pressure (MAP) was measured noninvasively. Heart rate and internal temperature were also recorded. Cutaneous vascular conductance (CVC) was calculated as LDV/MAP. During the initial cold stress, performed 130 min after bretylium treatment, CVC at treated sites fell by an average of 0.3 +/- 3.2% (P greater than 0.10) and at untreated sites by 29.2 +/- 4.1% (P less than 0.001 between sites). During heat stress, CVC at treated sites rose by 419 +/- 66% and at control sites, by 517 +/- 90% (P greater than 0.10 between sites). The internal temperature threshold for cutaneous vasodilation was not statistically different between sites (P greater than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589515 TI - Microvascular responses in copper-deficient rats. AB - In this study on copper deficiency, the rat crewmaster microcirculation was used as a model for endogenous histamine release and platelet thrombi formation. Male Sprague-Dawley rats were fed either a copper-supplemented diet (CuS, 5 ppm) or a copper-deficient diet (CuD, 0 ppm) for 5 wk before experimentation. The crewmasters of anesthetized rats were spread in a Krebs-filed tissue bath. In venules of CuS animals, photoactivation of intravascular fluorescein isothiocyanate tagged to bovine serum albumin caused significant platelet aggregation and reduction of red blood cell column diameter (RBCCD) by 40 min and stasis of flow by 60 min. In CuD animals there was only minor platelet aggregation and no reduction in RBCCD. Platelet aggregometry studies did not demonstrate reduced platelet aggregation in the CuD group, suggesting that copper deficiency alters the endothelium to inhibit adhesion. Compound 48/80 (1.0 and 10.0 microgram/ml) induced macromolecular leakage in both CuS and CuD groups, with the response in the CuD animals being significantly greater. The results demonstrate that copper deficiency results in alterations of the regulatory mechanisms governing inflammation and thrombosis. PMID- 2589516 TI - Kinetics of ATP-sensitive K+ channel revealed with oil-gate concentration jump method. AB - Kinetics for gating the ATP-sensitive K+ channel was studied by exposing the inside-out patch to instantaneous changes in the intracellular concentration of ATP ( [ATP]i) using the oil-gate concentration jump technique in guinea pig ventricular cells. The closing time course of the channel after increasing [ATP]i was exponential with a time constant (tau), which decreased with increasing [ATP]i. The linear 1/tau - [ATP]i relation revealed two different binding (closing) rate constants (mu) of 51.7 and 5.6 mM-1.s-1 and predicted a common unbinding (opening) rate constant (lambda) of 3.2 s-1. A variable latent period was observed before channel opening when [ATP]i was decreased. The mechanism of latency is not clear. Once the channel started to open at the change lowering [ATP]i, the opening time course was exponential. Measurements of the exponential tau obtained at 0 mM [ATP]i were divided into two groups with corresponding lambda of 2.8 and 20.1 s-1, respectively. The former agrees with the predicted value of 3.2 s-1, but in the latter case, tau for opening increased as [ATP]i was increased. This increase in tau was attributed to a decrease of lambda, which approached an asymptotic value of 3.2 s-1. We conclude that binding and unbinding of one molecule of ATP determine the gating of ATP-sensitive K+ channel. Different pairs of mu and lambda result in four types of gating patterns and practically two states of sensitivities to ATP. PMID- 2589517 TI - Microcirculatory responses in cat sartorius muscle to hemorrhagic hypotension. AB - The purpose of this study was to examine changes in the microcirculation that might explain the rise in vascular resistance during hemorrhagic hypotension. Diameter and red blood cell velocity of microcirculatory vessels in exteriorized cat sartorius muscles were studied during 4 h of hemorrhagic hypotension at 60 mmHg. During hypotension, vascular resistance of the muscles rose approximately 70% while calculated volume flow in arterioles and venules fell to about the same degree. Average red blood cell velocity for all capillaries showed a comparable decline. Red blood cell flow stopped in approximately 60% of capillaries, but the extent of stoppage varied greatly among capillary fields. Arterioles larger than 45 microns constricted 9-29%, with the largest arterioles showing the greatest constriction. Arterioles smaller than 45 microns dilated 34-56%, with the smallest arterioles showing the greatest dilation. Venular diameter did not change with hemorrhage. The predominance of arteriolar dilation, especially in the later stages of hypotension, should lead to a fall in vascular resistance of the muscle. This effect may be offset by constriction of arteries outside the microcirculatory field observed and blockage of capillaries or venules by formed elements. PMID- 2589518 TI - Adenosine and cerebral capillary perfusion and blood flow during middle cerebral artery occlusion. AB - The effects of adenosine on regional cerebral blood flow and indexes of the total and perfused microvascular bed were studied after 1 h of middle cerebral artery occlusion in the anesthetized rat. Iodo[14C]antipyrine was used to determine cerebral blood flow. Fluorescein isothiocyanate-dextran was used to study the perfused microvasculature, and an alkaline phosphatase stain was used to identify the total bed. Mean arterial blood pressure was significantly reduced by adenosine. Cerebral blood flow increased significantly by 75%, except in the flow restricted cortex where flow averaged 28 +/- 15 (SD) ml.min-1.100 g-1 in control and 34 +/- 33 ml.min-1.100 g-1 in adenosine-treated animals. No significant regional structural differences were observed within the microvascular beds of the two groups. The percentage of the microvascular volume perfused increased significantly in all brain regions in the adenosine-treated rats, including the flow-restricted cortex. The percent perfused arteriolar volume in the flow restricted cortex was 30 +/- 12% in control and 95 +/- 3% in adenosine-treated animals. Similar values for the capillary bed were 22 +/- 10% in control and 54 +/- 3% in adenosine-treated rats. These results indicate a maintenance of flow with a reduction in diffusion distances in the flow-restricted cortex after treatment with adenosine. PMID- 2589519 TI - Intracellular magnesium affects I(K) in single frog atrial cells. AB - Voltage-clamp experiments on single frog (Rana pipiens) atrial cells using whole cell recording techniques revealed that the addition of MgCl2 to the 150 mM KCl patch pipette solution influenced the voltage- and time-dependent potassium current (IK). After rupture of the membrane patch under the tip of the pipette, IK increased with time when the pipette solution was magnesium free, but decreased slightly when the solution contained 1.5 mM MgCl2. More dramatic decreases in IK occurred when the solution contained 3.0 or 10 mM MgCl2. In addition to suppressing the magnitude of IK, the activation rate of this current was enhanced by 10 mM MgCl2 but was not affected by 1.5 or 3 mM MgCl2. Other chloride salts containing mono-, di-, or trivalent cations were used to demonstrate that the effects of MgCl2 on IK were not related to alterations in ionic strength, osmolality, or chloride concentration produced by adding MgCl2 to the pipette solution. Our results suggest that changes in the intracellular magnesium concentration influence IK as the pipette solution exchanges with the intracellular fluid. PMID- 2589520 TI - Regional myocardial flow heterogeneity explained with fractal networks. AB - There is marked heterogeneity in regional myocardial blood flow. To explain how the distribution of flow broadens with an increase in the spatial resolution of the measurement, we developed fractal models for vascular networks. A dichotomous branching network of vessels represents the arterial tree and connects to a similar venous network. A small difference in vessel lengths and radii between the two daughter vessels, with the same degree of asymmetry at each branch generation, predicts the dependence of the relative dispersion (mean +/- SD) on spatial resolution of the perfusion measurement reasonably well. When the degree of asymmetry increases with successive branching, a better fit to data on sheep and baboons results. When the asymmetry is random, a satisfactory fit is found. These models show that a difference in flow of 20% between the daughter vessels at a branch point gives a relative dispersion of flow of approximately 30% when the heart is divided into 100-200 pieces. Although these simple models do not represent anatomic features accurately, they provide valuable insight on the heterogeneity of flow within the heart. PMID- 2589521 TI - Effects of endothelium regeneration on canine coronary artery function. AB - During coronary catheterization under general anesthesia, the endothelium of a portion of the proximal left circumflex coronary artery of dogs was removed (injured). Segments from the denuded and normal (distal circumflex and left anterior descending coronary) regions were removed immediately in some animals (acute studies) or 5 wk after the injury in other animals (chronic studies). No significant differences in passive mechanics or active stress normalized to medial thickness were found between segments from normal and denuded regions in acute studies or normal and injured segments in chronic studies. Intimal thickening was found in the chronically injured segments, which averaged 32% of the total media-adventitia thickness. No significant differences were found in potassium dose-response relations in acute or chronic studies. Maximum responses to serotonin were increased in acutely denuded but not in chronically injured segments. Sensitivity to serotonin was increased in chronically injured but not acutely denuded segments. Endothelium-dependent relaxation responses produced by acetylcholine, bradykinin, and the Ca2+ ionophore A23187 were all depressed in chronically injured segments compared with normal, as were relaxation responses to sodium nitroprusside. In acutely denuded segments, the former agents produced only small contractions at high doses, whereas nitroprusside relaxations were augmented compared with sites with intact endothelium. Relaxation responses to isoproterenol and forskolin were not significantly affected by acute denudation or by chronic injury. The results of this study suggest a "chronic" depression of relaxation responses mediated by the guanosine 3',5'-cyclic monophosphate pathway and increased serotonin vasoconstriction sensitivity in arteries 5 wk after an endothelial denudation injury. PMID- 2589522 TI - Arteriovenous oximeter for O2 content difference, O2 saturations, and hemoglobin content. AB - We combined two spectrophotometric oximeters to measure continuously and simultaneously arteriovenous O2 content difference (AVOD) as well as arterial and venous oxyhemoglobin saturations (SaO2, SvO2) and total hemoglobin concentration (Hb). AVOD of the flowing arterial and venous whole blood was determined by the method of Guyton et al. (J. Appl. Physiol. 10: 158-163, 1957) and Shepherd and Burgar [Am. J. Physiol. 232 (Heart Circ. Physiol. 1): H437-H440, 1977]. The new arteriovenous oximeter was tested in dog experiments in which SaO2, SvO2, Hb, and AVOD were variously changed by temporary suffocation, electric muscle stimulation, hemorrhage and transfusion, and hemodilution with saline. AVOD, SaO2, SvO2, and Hb were compared with the data of the arterial and venous blood sampled near the oximeter cuvettes and measured with an IL282 CO oximeter. In one dog experiment and one in vitro blood experiment, AVOD data of the same arterial and venous blood were compared by connecting the present oximeter in series with an A-VOX Systems oximeter developed by Shepherd and Burgar. The results showed that the new arteriovenous oximeter can continuously measure AVOD, SaO2, SvO2, and Hb over wide ranges with reasonable accuracy. PMID- 2589524 TI - Intracellular Ca2+ and force determined simultaneously in isolated resistance arteries. AB - A method is described for the simultaneous measurement of intracellular Ca2+ ([Ca2+]i) and force generation in isolated resistance arteries using the fluorescent Ca2+ indicator fura-2. Branch II mesenteric resistance arteries were isolated from 12-wk-old Wistar-Kyoto rats and mounted in a wire myograph. The myograph was placed on the stage of a compound microscope interfaced with a dual excitation wavelength fluorometer, and the tissue was loaded with fura-2 by incubation over a 30-min period with the cell-permeable form of the dye. When stimulated with physiological salt solution containing 100 mM KCl and 10 microM norepinephrine, a rapid and transient increase in [Ca2+], was observed to precede active force development and plateau at approximately 60% of the maximal level after 50 s. Washout of the agonists induced relaxation of these small arteries, consisting of an 85% decline in active tension over 100 s and a fall in [Ca2+]i to 50% of prerelaxation level over the same time period. Forskolin (1 microM), which increases intracellular adenosine 3',5'-cyclic monophosphate, induced a 50% relaxation over a 150-s period that was preceded by a fall in [Ca2+]i. Nearly identical results were obtained with 100 microM sodium nitroprusside, which stimulates intracellular guanosine 3',5'-cyclic monophosphate production. These findings indicate that the initiating event of forskolin- and sodium nitroprusside-induced relaxation may be a reduction of [Ca2+]i. The method described is useful for examining basic physiological events and Ca2+-related mechanisms of action of vasoactive compounds in isolated resistance arteries. PMID- 2589523 TI - Contractile function of isolated feline cardiocytes in response to viscous loading. AB - The classical force-velocity relationship is a standard measure of the contractile function of isolated linear cardiac muscle, but no such simple index of contractile function exists for the isolated mammalian cardiocyte. Therefore, this study established an analogous viscosity-velocity relationship for the characterization of cardiocyte contractile function. For this purpose, force was imposed on unfettered adult feline cardiocytes as a series of defined viscous loads, which provided resistance to cardiocyte shape changes during contraction. This was done by increasing the viscosity of the Krebs superfusate (37 degrees C, pH 7.4) in graded, reproducible steps from 1 to 500 centipoise by the addition of methylcellulose. Sarcomere motion within each contracting cardiocyte was measured as movement of the diffraction pattern cast onto a photodiode array by a laser beam passing through the cell. Both the rate and extent of sarcomere shortening varied inversely with increasing viscosity, whereas neither resting sarcomere length nor osmolarity was altered. Further, increased inotropism effected by paired-pulse stimulation of cardiocytes caused an upward shift of the entire viscosity-velocity relationship. Thus the cardiocyte viscosity-velocity relationship is analogous in form to the force-velocity relationship of isolated linear cardiac muscle and provides a simple reproducible method for characterizing the contractile performance of relatively large numbers of cardiocytes isolated from a single specimen of myocardium. PMID- 2589525 TI - Postocclusive cerebral hyperemia is markedly attenuated by chronic trigeminal ganglionectomy. AB - Marked hyperemia may develop in brain following temporary cessation of blood flow and is associated with the morbidity following cardiac arrest, stroke, and head injury. Regional cerebral blood flow was measured using radiolabeled microspheres and compared in 10 symmetrical regions after chronic unilateral trigeminal ganglionectomy (n = 8), trigeminal rhizotomy (n = 4), or sham operation (n = 4) following 10 min of combined brachiocephalic-left subclavian occlusion and hypotension (mean arterial blood pressure less than 50 mmHg) in cats. Blood flow was symmetrical at rest in the three groups and was undetectable during the ischemic period. Within 30 min after re-establishing flow, values in cortical gray matter increased symmetrically to approximately 250 ml.100 g-1.min-1 in the rhizotomy and the sham groups. Increases of similar magnitude were measured on the intact side following trigeminal ganglionectomy but flow was attenuated by greater than 50% ipsilateral to the ganglionectomy. Marked hyperemia developed during reperfusion in thalamus, caudate, deep cortical white matter, midbrain, and pons, but no asymmetries were present in the three groups. These data suggest that cortical hyperemia is mediated by trigeminal neurogenic mechanisms via axonal reflexlike mechanisms and suggest the importance of therapeutic strategies based on blockade of this nerve or its constituent neuropeptides. PMID- 2589526 TI - Evidence for adenosine receptor-mediated hyperpolarization in coronary smooth muscle. AB - The effects of adenosine and its analogues, 5'-N-ethyl-carboxamidoadenosine (NECA) and 2-chloroadenosine (CAD), were studied on resting membrane potential of bovine coronary artery. The resting membrane potential averaged -51 +/- 1 mV. KCl (50 mM) caused a significant decrease of the resting membrane potential (-30 +/- 1 mV). In separate series of experiments suffusion of the arterial strips with adenosine, NECA, or CAD, at concentrations of 10(-5)M, produced significant increases in resting membrane potential (-68 +/- 1, -80 +/- 2, and -88 +/- 4 mV, respectively). The hyperpolarizing responses to adenosine, NECA, and CAD appeared to have been mediated by an adenosine receptor, since they were blocked by the adenosine receptor antagonist, 8-phenyltheophylline (10(-5) M). The data suggest that activation of an adenosine receptor can result in hyperpolarization of coronary smooth muscle cells. PMID- 2589528 TI - A1 cell group mediates solitary nucleus excitation of supraoptic vasopressin cells. AB - Stimulation of the nucleus tractus solitarius (NTS) excites putative vasopressin secreting cells of the supraoptic nucleus (SON) via a catecholaminergic projection to hypothalamus. Despite recent evidence of a direct catecholaminergic projection from NTS to SON, we have performed single-unit recording experiments in pentobarbital sodium-anesthetized rats to investigate the possibility that NTS stimulation effects on SON vasopressin cells are indirect, being relayed via the A1 noradrenergic cell group of the caudal ventrolateral medulla. The effects of single-pulse NTS and A1 region stimulation on the activity of antidromically identified SON neurosecretory cells that had been functionally characterized as vasopressin secreting were compared. NTS stimulation excited 81% of all putative vasopressin-secreting cells tested (n = 83), with a mean onset latency of 51 +/- 1 ms. A1 region stimulation excited 76% of all cells tested and 90% of units responsive to NTS stimulation, with a mean latency of 39 +/- 1 ms. Consistent with previous work NTS stimulation excited only a minority of oxytocin cells tested (3/13), and of these two-thirds also responded to A1 stimulation. Bilateral electrolytic lesions of the A1 region abolished the effects of NTS stimulation on putative vasopressin cells. Ipsilateral A1 region injections of the inhibitory neurotransmitter gamma-amino-butyric acid reversibly blocked NTS stimulation effects on putative vasopressin cells in animals where the contralateral A1 region had already been lesioned. These results support the proposal that excitation of SON vasopressin-secreting cells after NTS stimulation is due to activation of a relay projection through the A1 noradrenergic cell group of the caudal ventrolateral medulla. PMID- 2589527 TI - Calcium-channel blockade in canine hemorrhagic shock. AB - The effect of verapamil (VER) resuscitation from shock on cardiac function, regional blood flow, as well as skeletal muscle transmembrane potential (TMP) and electrolyte redistribution were studied. Two hours of hypotensive shock in the dog significantly impaired cardiac function and coronary perfusion; TMP fell from 89.9 +/- 0.9 to 75.1 +/- 1.2 mV. Skeletal muscle (SMS) extracellular water decreased 40 +/- 2%, whereas intracellular sodium and chloride increased and intracellular potassium fell. Serum hypocalcemia was accompanied by a significant rise in total myocardial tissue calcium (from 312 +/- 20 to 415 +/- 21 micrograms/g dry wt; P = 0.01); total SMS tissue calcium tended to increase during this time (from 259 +/- 24 to 305 +/- 46 micrograms/g dry wt). After 2 h of shock, all dogs received shed blood and lactated Ringer solution (60 ml/kg); 21 dogs received VER, 20 micrograms/kg with fluid resuscitation; 21 dogs received fluid resuscitation only. Volume replacement improved hemodynamic function to a similar extent in all dogs. However, TMP, intracellular water, sodium, and potassium returned closer to base-line values after VER compared with dogs given only fluid resuscitation. SMS calcium was lower in VER dogs (148 +/- 4 micrograms/g) compared with dogs treated with fluid alone (322 +/- 24 micrograms/g, P = 0.01). Myocardial calcium fell in all dogs after volume replacement regardless of calcium-channel blockade (VER: 148 +/- 8, Ringer: 165 +/- 17 micrograms/g; P greater than 0.05). Our data indicate a potential role for calcium-entry blockade in the treatment of hemorrhagic shock. PMID- 2589529 TI - Renal sympathetic nerve activity and plasma catecholamines during eating in cats. AB - We measured renal sympathetic nerve activity (RNA) and arterial plasma concentration of norepinephrine (NE) and epinephrine (EPI) before, during, and after eating in six conscious cats. Eating continued for a period of 5 min. RNA, heart rate (HR), and arterial blood pressure (AP) increased almost simultaneously with the onset of eating and reached a maximum value of 192%, 221 beats/min, and 121 mmHg at 2.5-5 min after the onset of eating, respectively. The plasma NE level increased significantly (P less than 0.05) during eating from the control value of 0.56 ng/ml and reached a maximum value of 1.33 ng/ml at 4.5-5 min, whereas the plasma EPI level did not change significantly from the control value of 0.12 ng/ml. The plasma levels of NE and EPI were unaffected by the blood samplings. The relationship between the changes in RNA and the plasma NE level during eating had a significant (P less than 0.05) positive correlation (r = 0.52). The result suggests that plasma NE concentration tends to increase with the rise in RNA during eating. PMID- 2589530 TI - Sex differences in central adrenergic control of vasopressin release. AB - Central adrenoreceptor-mediated regulation of vasopressin secretion and cardiovascular function was studied in male rats and female rats in specific estrous cycle phases. In conscious, unrestrained rats with intracerebroventricular (icv) cannulas and femoral artery and vein catheters, plasma arginine vasopressin concentration (PAVP), mean arterial blood pressure (MABP), and heart rate (HR) were determined before and 5 and 15 min after icv injection of 10 micrograms norepinephrine or 50 micrograms phenylephrine. Norepinephrine (icv) increased PAVP in proestrus and metestrus four and three times (P less than 0.01 and 0.05, respectively) more than in males. Norepinephrine induced similar MABP elevations (P less than 0.01) in males and females in all cycle phases; HR decreased only in proestrus, estrus, and metestrus (P less than 0.01). The increase in PAVP after icv phenylephrine was four and three times greater in proestrous and diestrous females (P less than 0.01 and 0.05, respectively) than in males. The proestrous MABP rise was three times that in males (P less than 0.05); HR decreased similarly in diestrus, proestrus, and males. These results suggest gonadal steroid hormones influence adrenoreceptor-mediated control of vasopressin secretion, MABP, and HR. PMID- 2589531 TI - Freezing-induced changes in the heart rate of wood frogs (Rana sylvatica). AB - During the first few hours of freezing the cardiovascular system must distribute cryoprotectant throughout the body of freeze-tolerant frogs. This study presents initial documentation of the changes in heart rate of wood frogs (Rana sylvatica) during nonlethal freezing. Heart rate was determined by measuring the electrocardiogram of frogs. Within 1 min of the onset of freezing the heart rate nearly doubled to approximately 8.0 beats/min. The heart rate began to slow after the first hour of the freeze, and the heart completely stopped beating near the completion of ice formation approximately 20 h later. Recordings from a single frog revealed that the heart beat resumes within 1 h after thawing and near normal function is achieved after only a few hours. The release of the latent heat of fusion caused a rise in body temperature (1.7 degrees C) for a few hours and was closely correlated with an increase in the heart rate. However, other factors such as reduction in blood volume, increase in blood viscosity, and progressive hypoxia may prominently influence cardiac function indirectly. Regardless, the heart functions long enough to distribute glucose throughout the body during the first few hours of the freeze. PMID- 2589532 TI - Responses to dehydration and rehydration during heat exposure in young and older men. AB - Body temperature, plasma responses, and subjective ratings of thirst and hotness were studied in 5 older men (OM, 61-67 yr) and 6 younger men (YM, 21-29 yr) during 180-min thermal dehydration and subsequent 60-min rehydration (45 degrees C, 25% relative humidity). Rectal temperature (Tre) increased more rapidly and to a greater magnitude in OM, while average total body sweat rates and chest sweat rates were not significantly different. During dehydration, both OM and YM lost similar body weight (1.52 +/- 0.11 vs. 1.55 +/- 0.22%, mean +/- SE). However, in OM, plasma volume (Pv) decreased (-11.3 +/- 2.8 vs. -4.9 +/- 2.9%), and plasma osmolality (Posm) increased to a greater extent (+5.0 +/- 0.32 vs. 1.1 +/- 0.24 mosmol/kg) compared with YM. On rehydration, OM and YM similarly replaced water debt (46.6 +/- 4.9 vs. 49.0 +/- 3.0%). Within 30 min of drinking, YM had restored Pv and Posm, whereas OM showed slower responses, restoring Posm after 60 min and Pv only after a subsequent 30 min at 25 degrees C. Despite a higher Tre and greater change in Pv and Posm, OM rated themselves less thirsty and not significantly hotter than YM. These findings suggest that aging results in decreased ability to maintain Tre during heat stress and that the mechanisms comprise a combination of alterations in body fluid distribution and perception. PMID- 2589533 TI - Response to palatability after area postrema lesions: a result of learned aversions. AB - The role of palatability, novelty, and food aversion in determining changes of food choice after ablation of the area postrema and caudal-medial aspect of the nucleus of the solitary tract (AP/cmNTS) is examined through a series of studies utilizing 24-h, two-food choice tests. On test days, the food that the animal has ingested since the time of lesioning or sham surgery is presented along with a novel food that varies in palatability. The results indicate that postlesion diet history is the major determinant of food choice by lesioned rats. Lesioned rats consistently take less of their familiar postlesion food than diet-matched controls, suggesting that the lesioned rats have developed an aversion to that food. Over-ingestion of the novel food may occur, but this outcome is not reliable. No indication that the animals' response to food palatability is affected by AP/cmNTS ablation was found. Learned aversion to a food ingested after AP/cmNTS ablation may account not only for changes of food preference after the lesion but also may be involved in the hypophagia and weight loss resulting from the ablation. PMID- 2589535 TI - Fluid secretion and microvillar ultrastructure in mosquito malpighian tubules. AB - The Malpighian tubules of fourth instar larvae, pupae, and female adults of the mosquito Aedes taeniorhynchus were examined with regard to in vitro fluid secretion rate and the ultrastructural features of the microvillar border of the primary cells. In vitro fluid secretion rates were determined after stimulation with 5-hydroxytryptamine. While larval tubules are capable of rapid fluid secretion, the tubules of pupae exhibit very low rates of secretion, indistinguishable from 0 nl/h. The capacity to secrete fluid returns after the pupal-adult molt and is further enhanced after blood feeding. Similar results were obtained in tubules stimulated in vitro with dibutyryl adenosine 3',5' cyclic monophosphate. Ultrastructural examination of the microvillar border of the primary cells of the Malpighian tubules revealed that the period of reduced secretion capacity in the pupal tubules is correlated with a marked reduction in microvillar volume, microvillar surface area, and mitochondrial content in the microvillar border. The results suggest that microvilli of a certain size and containing extensions of mitochondria are required for rapid fluid transport. The absence of these conditions in pupal tubules cannot be overcome by in vitro stimulation with known secretagogues and therefore represents a physiological limit on transport performance in the pupal tubules of mosquitoes. PMID- 2589534 TI - Atropine-induced cutaneous vasodilation decreases esophageal temperature during exercise. AB - Four healthy adult males volunteered for this study, which followed informed consent procedures administered by our local Human Use Committee. Esophageal (Tes) and mean skin (Tsk, eight site) temperatures, forearm sweating rate (ms), metabolism (M), heart rate (HR), and forearm blood flow (FBF) were measured at rest and during forearm blood flow (FBF) were measured at rest and during exercise [55% oxygen consumption (Vo2) peak] during control experiments and after 2 mg im atropine (ATR). Experiments were randomized and separated by at least 72 h. ATR increased heart rate at rest by 15 beats/min and during exercise by 24 beats/min. ATR decreased whole body sweating by 57%. All eight local skin temperatures were higher in ATR than in control. Tsk was 32.6 degrees C in ATR and 31.0 degrees C in control (P less than 0.01). During exercise, ATR increased vasodilation of the forearm compared with control. The slope of FBF to Tes increased over 300% in ATR experiments compared with control (P less than 0.05). The higher sensible heat flux from this vasodilation decreased Tes during exercise, which further decreased sweating. Skin blood flow remained elevated as Tes decreased, suggesting that local vasodilatory factors promoted atropine induced cutaneous vasodilation. PMID- 2589536 TI - Effects of simulated weightlessness on rat osteocalcin and bone calcium. AB - Some of the musculoskeletal changes that occur in growing rats during spaceflight are simulated by a model that selectively unloads the hindlimbs while maintaining normal weight bearing on the forelimbs. Using this model we studied the response of mineral and the mineral-binding protein osteocalcin (OC) in the third lumbar vertebra (L3) and the femoral midshaft to periods of unweighting from 2 to 28 days. Serum OC decreased by 25%, consistent with a decreased rate of bone growth, during the first week of suspension and returned toward control values after 15 days. The L3 and femur weighed 20% less than control bones after 10-28 days. OC content of L3 and femur diaphysis were lower after 7 days of suspension and returned to normal levels at 28 days, whereas Ca content rose slightly at 5 days then decreased sharply. OC:Ca ratio was also affected. The data suggest that unweighting affects formation and deposition of OC and Ca differently depending on bone location and duration of unweighting. Both serum and bone OC are highly sensitive indicators of disruption of osteoblast activity by altered skeletal loading. PMID- 2589537 TI - Short photoperiod and cold activate brown fat lipoprotein lipase in the Djungarian hamster. AB - Activation of lipoprotein lipase (LPL) in brown fat of the Djungarian hamster ensures substrate supply for nonshivering thermogenesis. Cold acclimation [5 degrees C ambient temperature (Ta)] in long photoperiod [light-dark (LD) 16:8] increased brown fat LPL activity from 4.7 to 22.7 nmol oleate.mg-1.min-1 within 1 day. Slight reduction of this high LPL activity was observed during prolonged cold exposure for up to 4 wk. Deacclimation (transfer from 5 to 23 degrees C Ta) caused total inactivation of brown fat LPL within 4 days. Short photoperiod (LD 8:16) also stimulates brown fat LPL activity. Its effect can be summarized by three different observations. At thermoneutrality short photoperiod elevated LPL activity to 7.1 instead of 4.7 nmol.mg-1.min-1 observed in long photoperiod. Second, at low ambient temperature short photoperiod reinforces the effect of cold acclimation. Maximum LPL activity of cold-exposed Djungarian hamsters averaged 23.7 nmol.mg-1.min-1 in long photoperiod and was elevated to 35.5 nmol.mg-1.min-1 in short photoperiod. Third, inactivation of LPL during deacclimation was delayed in short photoperiod. These results demonstrate that photoperiod as well as ambient temperature may be cooperatively used as environmental cues for seasonal acclimation of brown fat substrate supply for nonshivering thermogenesis. PMID- 2589538 TI - Influence of preweaning food intake on body composition of young adult baboons. AB - The hypothesis that infant overnutrition increases fat cell number and promotes obesity in the young adult primate was tested. Newborn baboons were fed similar volumes of Similac formulas with caloric densities of 40.5 (underfed, n = 8), 67.5 (normally fed, n = 12), and 94.5 (overfed, n = 12) kcal/100 g formula until 4 mo of age. Afterwards all baboons were fed the same diet until they were young adults. At 5 yr of age body composition, mean fat cell size, and total fat cell number were measured. Infant food intake did not significantly influence body composition or fat cell number in the 5-yr-old male baboons. Five-year-old female baboons, overfed as infants, had significantly greater body fat mass, percent of body mass that was fat, and mean fat cell volume compared with females that were underfed or normally fed as infants. There was no difference in total fat cell number between the obese baboons that were overfed as infants and the lean baboons that were underfed or normally fed as infants. Fat cell number was not associated with body fat content; males had more fat cells than did females. These results demonstrate that infant overnutrition in a primate species promotes obesity in young adult females by increasing primarily fat cell size and not fat cell number. PMID- 2589539 TI - In vivo measurement of total body magnesium and manganese in rats. AB - Mg and Mn are essential minerals in many biological processes. Thus knowledge of their absolute amounts and how those amounts may be altered is important. In the past the in vivo measurement of Mg in animals was limited by both the poor geometry of the counting system and the requirement for multiple counts of the animal over several hours. We have developed a neutron activation technique for the direct in vivo measurement of total body Mg and Mn in the rat. The counting system adapted for the technique has a response that is relatively invariant (+/- 2.5%) to differences in body size. A least-squares curve fitting technique was developed that requires only a single 5-min count of the animal. Our in vivo values for body Mg and Mn were in excellent agreement (+/- 2.0%) with the results of total carcass analysis using atomic absorption. Longitudinal changes in total body Mg and Mn were examined in vivo in two groups of animals maintained on test diets that contained different amounts of Mg. PMID- 2589540 TI - Vagal cardiopulmonary baroreflex activation during phenylephrine infusion. AB - Phenylephrine infusion (PE) has been used to raise arterial pressure (BP) in order to investigate reflex responses mediated by sinoaortic baroreflexes (SAB). Increases in cardiac filling pressures have been reported during PE. Our experiments determined whether PE selectively activates SAB without activation of vagal cardiopulmonary baroreflexes (CPR). We measured changes in mean BP, mean pulmonary arterial pressure (PAP), and renal sympathetic nerve activity (RSNA) during PE in alpha-chloralose-anesthetized dogs before and after sinoaortic denervation (SAD; n = 10), selective vagotomy (n = 9), or SAD and vagotomy (n = 4). PE elevated both BP and PAP in all dogs studied. In dogs with SAB and CPR intact, RSNA was reflexively inhibited (% change RSNA: -76.3 +/- 4.7). In SAD dogs, inhibition of RSNA was significantly attenuated but not abolished (% change RSNA: -27.5 +/- 11.8). This inhibition after SAD correlated closely with increases in PAP. Small BP changes (10 mmHg) were associated with insignificant changes in PAP and RSNA. Volume expansion after SAD produced changes in PAP and RSNA similar to those produced by PE. After selective vagotomy, the sensitivity (% change RSNA/mmHg change BP) of the reflex elicited by PE was significantly decreased (-2.7 +/- 0.03 pre vs. -1.8 +/- 0.12 post; P = 0.01). PE failed to change RSNA after combined SAD and vagotomy. We conclude that vagal CPR contribute to reflex inhibition of RSNA during PE except when elevations of BP are small. PMID- 2589541 TI - Ventrolateral medullary neurons modulate pressor reflex to muscular contraction. AB - Cardiorespiratory alterations during exercise are mediated through feedback from contracting muscles and descending drive from rostral brain sites such as the posterior hypothalamus. The role of medullary sites, which process this information, was examined in this study. In anesthetized cats, muscular contraction elicited by stimulation of L7 and S1 ventral roots and electrical stimulation of sites in the posterior hypothalamus both evoked increases in arterial pressure, heart rate, and minute ventilation. The reflex increase in arterial pressure produced by muscular contraction was attenuated significantly 15-20 min after bilateral microinjections of an excitatory amino acid (EAA) receptor antagonist, kynurenic acid (KYN), into the ventrolateral medulla (VLM). The reflex increase in arterial pressure evoked by muscular contraction returned to control levels 90 min after VLM microinjections of KYN. Microinjection of KYN into the VLM had no effect on the cardiorespiratory responses to posterior hypothalamic stimulation. These findings suggest that neurons in the VLM modulate the reflex pressor response evoked by muscular contraction. This reflex may be mediated through an interaction with EAA receptors on neurons in the VLM. PMID- 2589543 TI - Effect of baroreceptor denervation on vasopressin and cortisol responses to angiotensin II infusion in conscious dogs. AB - Recent studies suggest that the pressor response to exogenous angiotensin II infusion may, through baroreceptor-dependent mechanisms, counteract the stimulatory effect of the peptide on vasopressin and adrenocorticotropic hormone (ACTH) secretion. To test this hypothesis, the effect of combined cardiac and sinoaortic baroreceptor denervation on the increases in plasma concentrations of vasopressin and cortisol (used as an index of ACTH secretion) produced by angiotensin II infusion was studied in conscious dogs. In eight intact dogs, 30 min angiotensin II infusions at 5, 10, and 20 ng.kg-1.min-1 increased mean arterial pressure from 108 +/- 5 to 126 +/- 5 mmHg, from 101 +/- 4 to 130 +/- 4 mmHg, and from 99 +/- 3 to 138 +/- 4 mmHg, respectively (P less than 0.001). Plasma cortisol concentration increased from 19 +/- 4 to 27 +/- 4 ng/ml, from 19 +/- 4 to 43 +/- 4 ng/ml, and from 19 +/- 4 to 71 +/- 6 ng/ml (P less than 0.01), and plasma vasopressin concentration increased from 2.2 +/- 0.3 to 3.1 +/- 0.3 pg/ml, from 2.3 +/- 0.3 to 3.5 +/- 0.4 pg/ml, and from 2.2 +/- 0.4 to 5.0 +/- 0.5 pg/ml (P less than 0.01). In five to six baroreceptor-denervated dogs, angiotensin II infusion produced increases in mean arterial pressure, plasma vasopressin concentration, and plasma cortisol concentration that were not consistently different from those in the intact dogs. These results demonstrate that baroreceptor denervation does not enhance the vasopressin or cortisol responses to angiotensin II infusion in conscious dogs. PMID- 2589544 TI - Tumor necrosis factor enhances glucose uptake by peripheral tissues. AB - Anesthetized dogs received a constant intravenous infusion of tumor necrosis factor (TNF) or saline over 6 h. Glucose kinetics were studied by determining the rate of glucose turnover and hindlimb substrate flux. Cardiovascular responses were monitored and concentrations of counterregulatory hormones were also measured. TNF infusion caused a fall in blood glucose concentration from 4.6 +/- 0.1 to 3.9 +/- 0.2 mmol/l by 6 h (P less than 0.05). This mild hypoglycemia was associated with increased circulating levels of cortisol, glucagon, and epinephrine. The rate of glucose production increased from 26.5 +/- 2.1 to 32.5 +/- 0.7 mumol.min-1.kg body wt-1 (P less than 0.05) over the 6-h infusion period; this response was associated with increased glucose disappearance (26.4 +/- 2.2 to 32.7 +/- 0.9 mumol.min-1.kg body wt-1, P less than 0.05) and enhanced clearance (5.7 +/- 0.5 to 9.0 +/- 0.6 ml.min-1.kg body wt-1, P less than 0.05). As blood glucose levels fell, hindlimb glucose uptake and glucose clearance increased markedly in TNF-infused animals as compared with controls despite a 50% fall in mean serum insulin concentration. The exchange of lactate, pyruvate, and total amino acid nitrogen across the hindlimbs was similar in both groups of animals. However, arterial concentrations of lactate and pyruvate rose to two to three times their initial values. The hypoglycemia associated with the infusion of TNF results from a disparity between the rate of glucose appearance and disappearance. There is an increased uptake of glucose across the hindlimb; this response appears to be independent of insulin concentrations and may be related to direct effects of TNF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589542 TI - Capsaicin attenuates hindbrain neuron responses to circulating cholecystokinin. AB - Capsaicin is a neurotoxin that destroys small sensory neurons with unmyelinated axons, including a subpopulation of vagal sensory neurons. Capsaicin treatment attenuates suppression of food intake induced by systemic administration of cholecystokinin (CCK) but not by gastric distension. However, both gastric distension and intravascular CCK alter the discharge of dorsal hindbrain neurons by a vagal mechanism. Therefore, it is plausible that some hindbrain neurons receive convergent input from capsaicin-sensitive vagal neurons that are responsive to CCK and also from capsaicin-insensitive neurons that are responsive to gastric distension. To investigate this possibility we made extracellular recordings from gastric distension-responsive hindbrain neurons during intra arterial cholecystokinin octapeptide (CCK-8) administration in anesthetized intact and capsaicin-pretreated rats. We found that capsaicin-pretreated rats exhibit attenuated neuronal discharge responses to CCK-8 but not to gastric distension. These results are consistent with the existence of convergent CCK sensitive and gastric distension-sensitive afferent inputs to hindbrain neurons and suggest that various gastrointestinal sensory modalities may be communicated to the brain by populations of neurons that can be distinguished by their sensitivity to neurotoxins. PMID- 2589545 TI - Sodium appetite and thirst in cattle subjected to dehydration. AB - Cows having free access to water (hydrated) or deprived of water for 26.5 h (dehydrated) were infused for 3 h with angiotensin II or captopril solutions intravenously (iv) or intracerebroventricularly (icv) beginning 1 h before access to 0.3 M NaHCO3/NaCl solution for 2 h. The results agree with the results of the experiments with the same agents and doses in Na-deficient cows. Only iv infusion of angiotensin II stimulated Na appetite and only icv infusion of angiotensin II stimulated thirst. Therefore, barriers to the penetration of angiotensin II in the brain determined the particular site of action and elicited response. Dehydration did not stimulate Na appetite and, as shown previously, Na deficiency did not stimulate thirst, but both behaviors seem to be influenced by angiotensin related mechanisms in the brain. The inability of iv angiotensin II to stimulate Na appetite in hydrated cows might be explained by the lack of a response caused by, and common to, Na deficiency and dehydration, e.g., upregulation of angiotensin II receptors, or reduced extracellular fluid volume. PMID- 2589546 TI - Bombesin affects feeding independent of a gastric mechanism or site of action. AB - Peripherally administered bombesin has been demonstrated to inhibit food intake in a variety of species. Although the behavioral actions of bombesin are well characterized, neither the site of action nor mechanism through which bombesin affects feeding has been demonstrated. To test the hypothesis that bombesin's feeding effects are through a gastric inhibitory mechanism or a gastric site of action we examined the potential relationship between the inhibition of gastric emptying and the inhibition of intake produced across a dose range of bombesin and compared the relative potency of bombesin analogues for inhibiting feeding with their affinity for gastric bombesin receptors. Comparisons of the inhibitions of gastric emptying and feeding produced by 2, 4, 8, or 16 micrograms/kg of bombesin revealed no relationship, and, in fact, no gastric inhibitory action was evident. The feeding inhibitory actions of dose ranges (100 pmol-100 nmol) of litorin, ranatensin, acetylated gastrin-releasing peptide-(20 27) [AcGRP-(20-27)] and bombesin-(8-14) fragment were assessed and compared with bombesin. These compounds inhibited feeding with a relative potency of bombesin greater than AcGRP-(20-27) greater than ranatensin greater than litorin greater than bombesin-(8-14). This rank order of potency differed from the relative affinity of these compounds for gastric bombesin receptors for which all of these compounds except bombesin-(8-14) have a greater affinity than does bombesin. The results of these two experiments suggest that bombesin's satiety actions are not mediated by a gastric inhibitory mechanism or through a gastric site of action. PMID- 2589547 TI - 24-hour blood pressure recordings in Dahl rats on high- and low-salt diets. AB - The goal of this study was to determine if the baroreflex abnormality previously shown in Dahl-sensitive (DS) rats would increase blood pressure and heart rate (HR) variability. Mean arterial pressure (MAP) and HR were sampled every 2 s for 24 h from Dahl-resistant (DR) and DS rats on low- and high-salt diets (n = 12-13 in each group). MAP +/- SD was significantly elevated in the DS rats on high-salt diets (DSH); the SD of MAP in the DSH rats was also significantly higher compared with similar measurements in rats on high-salt diets (DRH) and DS rats on low salt diets (DSL) when SD was divided by MAP. MAP was higher at night than during the day in the DSH rats. In contrast, HR and HR variability were not significantly different between the groups. The baroreflex control of HR, determined by means of graded injections of phenylephrine, was least in the DSH rats and increased, respectively, with DSL rats, DRH rats, and DR rats on low salt diets. There was no significant correlation between the baroreflex control of HR and MAP or the SD of MAP in the DSH rats, suggesting that there is not a simple relationship between baroreflex gain and the overall behavior of MAP in DSH rats. PMID- 2589548 TI - Protein phosphorylation in isolated hepatocytes of septic and endotoxemic rats. AB - The purpose of this study was to investigate possible alterations induced by sepsis and endotoxicosis in the late phase of Ca2+-dependent signaling in rat liver. Hepatocytes isolated from septic or chronically endotoxin (ET)-treated rats were labeled with [32P]H3PO4 and stimulated with various agents. Proteins were resolved by one-dimensional polyacrylamide gel electrophoresis and autoradiographed. Vasopressin (VP)- and phenylephrine (PE)-induced responses were attenuated in both septic and ET-treated rats for cytosolic and membrane proteins compared with their respective controls. Glucagon and 12-O-myristate phorbol-13 acetate (TPA) affected only the phosphorylation of membrane proteins. Glucagon induced changes in the phosphorylation of membrane proteins were affected by both sepsis and endotoxicosis, whereas TPA-stimulated phosphorylation was lowered only in endotoxicosis. Response to the Ca2+ ionophore A23187 was depressed in septic rats for cytosolic proteins. The phosphorylation of two cytosolic proteins, i.e., 93 and 61 kDa (previously identified as glycogen phosphorylase and pyruvate kinase, respectively), in response to VP, PE, and A23187 was severely impaired by endotoxicosis and sepsis. TPA did not affect the phosphorylation state of these two proteins. The results show that sepsis and endotoxicosis produce perturbations of the phosphorylation step in Ca2+ transmembrane signaling. Such changes can explain alterations of glycogenolysis and gluconeogenesis associated with sepsis and endotoxicosis. PMID- 2589549 TI - Effect of ovariectomy and estradiol on unity of female rat circadian rhythms. AB - Sixteen rats were ovariectomized and given either a 1-cm implant of crystalline estradiol-17 beta (eight rats) or an empty implant (eight rats). A further six rats were sham ovariectomized and given empty implants, and eight rats were left unoperated. The rats were exposed to 70 days of constant dim light (LL) with a maximum illumination level of 20 lx, and circadian running and drinking rhythms were monitored. In LL, both the running and drinking activity rhythms of the ovariectomized, blank-implanted rats became markedly disrupted, whereas unoperated and sham-operated rats maintained unified rhythms. Estradiol-implanted rats developed fewer rhythm desynchronies, and the majority displayed a single band of free-running activity. Rather than being arrhythmic, the activity of the LL-exposed ovariectomized rats appeared to contain several free-running components. Thus these data are consistent with the concept of a multioscillatory basis to the circadian system and support a role for the ovary and its hormone estradiol in the maintenance of coherence between component oscillators. PMID- 2589550 TI - Cerebral oxidative metabolism in lambs during perinatal period: relationship to electrocortical state. AB - Cerebral oxidative metabolism and regional blood flow were studied, with changes in behavioral state over the immediate perinatal period, to determine the change in cerebral metabolism at birth and the relationship to behavioral activity. Nine unanesthetized fetal sheep (139-142 days gestation) were each studied during a period of high-voltage and low-voltage electrocorticogram (ECOG) activity and then again after cesarean delivery at 2 h of age while awake and at 24 h of age while awake and during a period of high-voltage ECOG sleep. Preductal arterial and sagittal vein blood samples were analyzed for O2 content, blood gases, and pH. Blood flow was measured with a radioactive microsphere technique. Cerebral oxidative metabolism showed no significant perinatal change, although a coupling to behavioral state was evident with significant increases during both the perinatal low-voltage ECOG state and the awake state at 24 h. Blood flow to the brain showed a significant perinatal decrease after birth and state-related increases during both the prenatal low-voltage ECOG state and the awake state at 24 h consistent with the tight coupling of flow and/or O2 delivery to metabolic needs reported for normal brain tissue. The cerebral metabolic rate of the prenatal low-voltage ECOG state suggested a level of functional excitation comparable with that of the awake state after birth, supporting the importance of the rapid-eye-movement (REM) state mechanism as a source of endogenous stimulation during the perinatal period of brain growth and development. PMID- 2589551 TI - Face validity of the DSM-III-R personality disorders. AB - A list of the 142 diagnostic criteria for the DSM-III-R personality disorders was sent to a national sample of psychiatrists and clinical psychologists. The criteria were presented in randomly scrambled order, and clinicians were asked to assign the criteria to their parent categories. The average clinician assigned 66% of the criteria to the actual parent categories. These results suggest that the face validity of many of the DSM-III-R personality disorder criteria is low. Moreover, it appears that there are high levels of overlap in meaning among the criteria for the histrionic/narcissistic, avoidant/dependent, and schizotypal/paranoid pairs of personality disorders. PMID- 2589552 TI - DSM-III-R personality disorders in patients with eating disorders. AB - The authors conducted a systematic examination of DSM-III-R personality disorders among 35 patients with eating disorders. Fifty-seven percent of the patients met the criteria for at least one axis II diagnosis; borderline, self-defeating, and avoidant were the most frequently assigned personality disorders. Forty percent of the patients were given two or more diagnoses, and 17% of the patients met criteria for five to seven diagnoses. No differences were found between patients with anorexia nervosa, anorexia and bulimia nervosa, and bulimia nervosa in the distribution of diagnoses or the frequency with which individual criteria (traits) were assigned. PMID- 2589553 TI - Depression and posttraumatic stress disorder in Southeast Asian refugees. AB - The authors report on 404 Southeast Asian refugees seen at a community clinic. Approximately three-quarters of these patients met DSM-III criteria for major depressive episode, and 14% had posttraumatic stress disorder. Complaints of pain and sleep disturbances were the predominant presenting symptoms. Most of the men were married, but more than 40% of the women were widowed. Between 15% and 30% of the patients reported specific traumatic experiences either in their homeland or during their escape. Widowhood and such traumatic experiences were positively correlated with more symptoms of depression and anxiety. PMID- 2589554 TI - Sexual abuse histories and sequelae in female psychiatric emergency room patients. AB - The charts of 100 nonpsychotic female patients in a psychiatric emergency room were reviewed to locate references to history of sexual molestation: 50 charts were selected at random from emergency room files, and 50 charts had been written by clinicians asked to query abuse history. A substantially higher rate of sexual abuse was found for patients who had been directly asked about sexual molestation (70%) than for the random sample (6%). Further analysis linked molestation history to suicidality, substance abuse, sexual difficulties, multiple psychiatric diagnoses, and axis II traits or disorders--especially borderline personality. Severe abuse and multiple abusers best predicted psychiatric sequelae. PMID- 2589555 TI - Current status of multiple personality disorder in India. AB - Three consecutive cases of multiple personality disorder seen over a period of 3 years at a psychiatric clinic in India are reported. The prevalence of this disorder at the clinic is about 0.15/1,000 patients per year. The authors discuss the infrequency of this diagnosis in India in contrast to the frequent diagnosis of possession syndrome for patients who have many of the same symptoms. Transcultural differences in diagnostic practices are also discussed. PMID- 2589556 TI - Individual differences in serum sodium levels in schizophrenic men with self induced water intoxication. AB - Eight men with chronic schizophrenia and self-induced water intoxication showed marked individual differences in their serum sodium levels. The severity of the intoxication symptoms reflected the amount and speed of change in sodium levels rather than the absolute sodium values. PMID- 2589557 TI - A case of fluoxetine-induced serum sickness. AB - After 3-4 weeks of taking fluoxetine for depression, a 27-year-old man developed fever, skin eruptions, arthralgia, and lymphadenopathy. His clinical symptoms and results of laboratory assessment were consistent with a diagnosis of serum sickness reaction to the fluoxetine. PMID- 2589558 TI - Prevalence estimates of pathological gambling in New Jersey and Maryland. AB - This survey of the gambling behavior of 1,750 adults in New Jersey and Maryland confirmed findings in New York State. The substantial differences between problem and pathological gamblers in the general population and those entering treatment programs have serious implications for prevention, outreach, and treatment efforts. PMID- 2589559 TI - Fluoxetine in the treatment of agitated dementia. PMID- 2589561 TI - Trazodone-fluoxetine combination for treatment of obsessive-compulsive disorder. PMID- 2589560 TI - Fluoxetine and nortriptyline combination therapy. PMID- 2589562 TI - Mania during fluoxetine treatment for recurrent depression. PMID- 2589563 TI - Carbamazepine and SIADH. PMID- 2589565 TI - Light therapy for seasonal bulimia. PMID- 2589564 TI - Naltrexone for treatment of self-injury. PMID- 2589566 TI - The literature on psychopathology in Japan. PMID- 2589567 TI - Psychiatrists and family practitioners. PMID- 2589568 TI - The Alzheimer's disease research imperative. PMID- 2589569 TI - Child psychiatry fellowship training. PMID- 2589570 TI - Psychotherapy integration--with a bias? PMID- 2589571 TI - Sleep disturbance and PTSD. PMID- 2589572 TI - Prostaglandins and organic affective syndrome. PMID- 2589573 TI - Psychotherapy of schizophrenia. PMID- 2589574 TI - The DST and outcome in schizophrenia. PMID- 2589576 TI - Participatory matching. PMID- 2589575 TI - Genetics and psychiatry. PMID- 2589577 TI - Where have all the students gone? PMID- 2589578 TI - Results of in-situ saphenous vein bypass to the foot. AB - To determine the efficacy of extending vascular reconstruction to the pedal vessels, the records of 115 in-situ saphenous vein bypasses to the infragenicular vessels were examined. Ninety-four percent were performed for limb-threatening ischemia and 6 percent for claudication. Ninety-one bypasses were to tibial vessels in the calf (Group 1), whereas severe disease of the tibial vessels in the calf necessitated bypass to arteries at the ankle and beyond in 24 (Group 2). Life-table analysis was used to calculate limb salvage, graft patency, and functional status for Group 1 and Group 2 36 months postoperatively; there were no statistical differences between groups with regard to these variables (p = 0.38). Diabetes had no impact on the success of reconstruction, and preoperative noninvasive testing was not predictive of graft failure in either group. Significantly, limb salvage closely paralleled graft patency and functional status, illustrating the severe disease in all patients. Patients with severe tibial-peroneal atherosclerosis may benefit from bypass grafting to the pedal arteries with a success rate equal to those done to more proximal sites. PMID- 2589579 TI - Extraanatomic bypass for peripheral arterial injuries. AB - Over an 8-year period, extraanatomic bypass grafting was performed for peripheral arterial injuries or infections in 12 patients. The indications for use of the technique were as follows: (1) extensive loss of soft tissue over arterial injury or avulsion; (2) wound infection with rupture of a previous arterial repair; or (3) combined infections in soft tissue and the underlying artery due to illicit drug injection. The technique involved excision of the injured or infected artery beyond the margins of the debrided wound and insertion of an autogenous saphenous vein as an extraanatomic bypass graft in a medial or lateral position around the wound. Shotgun wounds were the mechanism of injury in six patients, whereas an extensive injury or infection in the brachial artery was present in eight patients. Successful wound coverage or closure was accomplished and distal arterial flow preserved in 11 patients, 5 of whom had residual neuromuscular or bony defects related to the magnitude of the original injury. PMID- 2589580 TI - Silent deep vein thrombosis in immobilized multiple trauma patients. AB - Although few trauma patients sustain fatal pulmonary embolism, a large population is at risk from nonfatal embolism due to unrecognized deep vein thrombosis (DVT). Thirty-eight of 39 immobilized trauma patients at bed rest for 10 days or longer had venographic study of their lower extremities to evaluate for the presence of silent DVT. Sixty percent of patients had silent DVT, with thrombi extending above the knee in half the patients with clot. DVT was documented in 67 percent of patients with major lower extremity fractures and 59 percent of patients without major fractures. DVT increased with increasing age but not with injury severity score. PMID- 2589581 TI - Prevention of amputation by diabetic education. AB - This prospective randomized study evaluated the influence of a simple education program on the incidence of lower extremity amputation in diabetic patients. Two hundred three patients were randomized into two groups: Group 1, education (103 patients, 203 limbs) and Group 2, no education (100 patients, 193 limbs). There were no significant differences in medical management or clinical risk factors between the two groups. The amputation rate was three times higher in Group 2 (21 of 177 limbs versus 7 of 177 limbs; p less than or equal to 0.025), the ulceration rate was three times higher in Group 2 (26 of 177 limbs versus 8 of 177 limbs; p less than or equal to 0.005), and there was no difference in the overall incidence of infection (2 of 177 limbs). Overall success in Group 1 was highly significantly different from Group 2 (160 of 177 limbs versus 128 of 177 limbs; p less than or equal to 0.0005). This study demonstrated that a simple education program significantly reduced the incidence of ulcer or foot and limb amputation in diabetic patients. PMID- 2589582 TI - Value of radiographs and bone scans in determining the need for therapy in diabetic patients with foot ulcers. AB - Thirty-two diabetic patients with foot ulcers were evaluated. Twenty-five patients had foot radiographs, technetium-99m bone scans, and wound and bone cultures; the remaining seven patients had all the studies except bone scanning. Bone changes compatible with osteitis were present on 15 of 32 foot radiographs (47 percent) and on 16 of 25 bone scans (64 percent). Bacterial growth was present in 27 of 32 wounds (84 percent) and 23 of 32 bone cultures (72 percent). Twelve of 23 patients (52 percent) with positive bone cultures had evidence of bone destruction and periosteal reaction on radiographs. The remaining 11 of 23 patients (48 percent) without radiographic signs of osteitis had bacterial growth from their bone cultures. Bone scans were positive in 12 of 18 patients (67 percent) with positive bone cultures and negative in 6 of 18 positive bone cultures (33 percent). We conclude that neither foot radiographs, technetium-99m bone scans, nor wound cultures should be used as the sole criterion for determining the use of antibiotic therapy or amputation in diabetic patients with foot ulcers. PMID- 2589583 TI - Conservative management of combined pancreatoduodenal injuries. AB - We have reviewed our recent 12-year experience in treating 62 patients with combined injuries to the pancreas and duodenum; 60 percent were the consequence of penetrating wounds and 40 percent due to blunt trauma. For analysis, grades I through V were assigned to reflect severity of injury. Grade I (16 percent) and II injuries (23 percent) were treated with simple repair and drainage. Grades III (19 percent) and IV (32 percent) were managed primarily by pyloric exclusion, whereas grade V injuries (10 percent) underwent pancreatoduodenectomy. Pancreatic and duodenal complications developed in 35 percent and 2 percent, respectively. The overall mortality was 19 percent; 83 percent died within the first 24 hours from exsanguination or severe head injury. Although no single procedure uniformly applies to the combined pancreatoduodenal trauma, active sump drainage of the pancreas, pyloric exclusion of the duodenum, and early nutritional support through needle catheter jejunostomy are the mainstay treatment principles. PMID- 2589584 TI - Multiple trauma and the burn patient. AB - Multiple trauma greatly complicates the care of the burn patient, whereas a burn often complicates the diagnosis and treatment of the trauma patient. One hundred seventy-six of 3,550 consecutive acute burn admissions received nonburn trauma. The majority of injuries were sustained in motor vehicle accidents (70), escaping fire (32), electrical burns with falls (24), scald burns associated with assault (22), and explosions (18). Eighty patients received orthopedic injuries, including major (47), minor (25), and multiple (28) fractures, 10 dislocations, and 4 open joints. Soft-tissue injury occurred in 91 patients, head injury in 30, thoracic trauma in 27, and abdominal injury in 15. Unstable orthopedic injuries were major contributors to morbidity. Early internal and external fixation permitted optimal mobilization and wound care. Awareness of the potential for multiple injuries and the team approach to these injuries are the most important factors in appropriate care. PMID- 2589585 TI - Utility of the cervical spine radiograph in pediatric trauma. AB - To determine the utility of the routine cervical spine radiograph, we reviewed all cervical spine radiographs obtained in pediatric trauma patients over a 2 1/2 year period at the Childrens Hospital of Los Angeles. Records of patients admitted with a documented cervical spine injury over a 20-year period were also reviewed. One hundred eighty-seven children had at least one cervical spine radiograph. Forty-six patients (25 percent) required at least one repeat study in an attempt to see all 7 vertebrae. Thirty-eight children (20 percent) had a second radiograph and 8 patients had a third study, all of which showed no injury. There was only one fracture seen during the 2 1/2-year time period. Of the 16 children admitted over the 20-year period, only 3 sustained an injury below the fourth cervical vertebra (C4), and all were over 8 years of age. All patients with cervical spine injury were either comatose or had symptoms referable to the neck. We conclude that the routine cervical spine radiograph in pediatric trauma is a very low-yield test. PMID- 2589586 TI - Antivenin and fasciotomy/debridement in the treatment of the severe rattlesnake bite. AB - This experimental study of severe rattlesnake envenomation compares antivenin alone, fasciotomy and debridement alone, and a combination of the two methods as definitive treatment. Superior survival and preservation of muscle function were observed in the animals treated with antivenin alone. PMID- 2589587 TI - Operative management of rural trauma over a 10-year period. AB - Trauma victims should in most cases be transported to the nearest trauma center as soon as possible after injury. Since this is not always feasible in underserved rural areas, the community hospital occasionally must function as the trauma center. From 1977 to 1987, while working in a rural community hospital in the northern Rocky Mountains, we operated on 83 patients with visceral and vascular injuries. The typical patient was a young man who sustained multiple injuries from motor vehicle or recreational accidents. Twenty-one patients had 27 major complications, and 2 died. Many small communities cannot afford helicopter based trauma systems. Conversely, however, distance and geographic barriers limit access to designated centers. Accordingly, rural surgeons cannot opt out of trauma care and must look to trauma surgeons to help in solving access problems. PMID- 2589588 TI - Trauma malpractice claims related to trauma level designation. AB - The purpose of the present study was to review a one-state experience (Arizona) with trauma malpractice claims as a function of hospital trauma level designation. A total of 191 cases covering 7 years was reviewed and analyzed. Three categories of treatment facilities were compared: American College of Surgeons-categorized Level I hospitals, all other hospitals, and outpatient treatment facilities. Only 22 percent of the malpractice claims were found in Level I facilities, whereas 58 percent were found in other hospitals and 20 percent came from outpatient facilities. Not surprisingly, the indemnity awards were more than two times higher in other hospitals than in Level I hospitals. However, the legal dollars spent in defense per claim were two times higher in Level I than either outpatient hospitals or outpatient treatment facilities, suggesting that Level I malpractice claims are more defensible. We have identified six areas of high potential liability and have made some suggestions for the reduction of risk management in those areas. PMID- 2589589 TI - A plea for sensible management of myocardial contusion. AB - The purpose of this study was to define the relative risk of life-threatening sequelae in patients at risk for myocardial contusion. During a 3-year period, 280 patients sustaining blunt chest trauma were admitted to the surgical intensive care unit to exclude myocardial contusion. Patients were evaluated by electrocardiogram and creatine phosphokinase (CPK) MB enzyme levels every 8 hours for a minimum of 48 hours. Myocardial contusion was identified in 35 patients (13 percent); the diagnosis was established by transient electrocardiographic changes (30), CPK-MB more than 3 percent (9) or both criteria (4). Two patients (1 percent) died from cardiac decompensation 4 and 12 hours postinjury, and seven (3 percent) required early (12 hours postinjury) intensive care unit treatment of arrhythmias or myocardial failure. None of the remaining 271 patients developed cardiac symptoms. This clinical experience underscores the low incidence of cardiac sequelae among patients at risk for myocardial contusion. Complications were always manifest within 12 hours of injury. The clinical diagnosis of myocardial contusion can be excluded pragmatically in the asymptomatic patient with a normal electrocardiogram and CPK-MB levels during the initial 24-hour postinjury period. PMID- 2589590 TI - Analysis of thirty-two patients with Schatzki's ring. AB - Schatzki's ring is a distinct anatomical entity associated with hiatal hernia; however, its significance is unclear. Thirty-two patients with a radiologically demonstrated Schatzki's ring were compared with 32 patients with hiatal hernia and no Schatzki's ring. Schatzki's ring was confirmed on endoscopy in 59 percent of patients. Seventy-five percent of patients with Schatzki's ring presented with dysphagia compared with 41 percent of control patients (p less than 0.01). Heartburn and regurgitation were less frequent than in control subjects (38 percent versus 91 percent, p less than 0.0001). Schatzki's ring patients were found to have a lower incidence of proven gastroesophageal reflux on 24-hour pH monitoring. Those with proven reflux were found to have a more efficient lower esophageal sphincter than control patients. Sixty-two percent of Schatzki's ring patients without proven reflux had a history of chronic ingestion of drugs known to be damaging to the esophageal mucosa, whereas only 26 percent of patients with reflux had this history. This was found in 16 percent of controls. Sixty-two percent of Schatzki's ring patients without reflux responded to a single dilatation compared with 37 percent of those with reflux. These findings suggest an etiologic relationship between pill lodgement and Schatzki's ring in patients without reflux and indicate that different therapy should be employed in these patients. PMID- 2589591 TI - Intraabdominal surgery during pregnancy. AB - Intraabdominal surgical disease during pregnancy can present a challenge in diagnosis and management for the obstetrician and surgeon. To examine the complications to the fetus and mother and the consequences of a delay in operative intervention, we retrospectively studied all pregnant patients over a 17-year period who had undergone abdominal surgery at one institution. A total of 92 abdominal operations were performed on 90 patients. During the same period, 41,532 deliveries occurred. One in 451 deliveries involved surgical procedures during pregnancy. Thirty-seven patients had surgery for acute appendicitis; 20 patients were operated on for ovarian abnormalities. Postoperatively, there were two maternal deaths: one from cardiac arrhythmia and the other from hepatic failure. The most common postoperative complication was premature labor (19 patients, 21 percent). In 16 of these patients, early tocolysis was begun without fetal loss. There were five fetal deaths. Forty-seven of 72 patients had term deliveries. Intraabdominal surgery during pregnancy carries an acceptable risk to the mother and fetus; complications are related to disease severity and operative delay rather than to the operative procedure itself. PMID- 2589592 TI - Factors predicting failure of medical therapy for gastric ulcers. AB - We reviewed the charts of all patients admitted with a diagnosis of gastric ulcer from January 1970 to December 1980. Multiple risk factors were recorded in patients receiving medical treatment and compared in those patients successfully treated medically versus those requiring operation after a failed course of medical treatment. One hundred patients were treated medically without surgical intervention, and 34 patients underwent operation after medical therapy failed. Significant risk factors in patients requiring operative therapy included smoking (p = 0.03), multiple trauma and sepsis (p = 0.02), large ulcers (p = 0.03), and multiple ulcers (p = 0.02). We have identified a set of factors associated with a high risk of failure of medical therapy. Patients with any of these risk factors may be treated most effectively by a limited trial of medical therapy with close follow-up. If their ulcer disease does not respond readily to standard medical therapy, they should be considered for early elective surgery. PMID- 2589593 TI - Rectopexy without resection for rectal prolapse. AB - Forty-three patients underwent simple posterior suture rectopexy for repair of rectal prolapse. Follow-up was obtained in 42 patients (mean 28 months). The recurrence rate was 2 percent (one patient). Postoperative morbidity and mortality were 20 percent and 0, respectively. The proportion of continent patients increased from 36 percent preoperatively to 74 percent postoperatively. Constipation increased after suture rectopexy but was managed conservatively. We believe that simple suture rectopexy offers a safe and effective alternative to other, more complex procedures for the treatment of rectal prolapse. PMID- 2589594 TI - Intestinal fistula complicating necrotizing pancreatitis. AB - Eight of 17 patients with necrotizing pancreatitis (47 percent) developed 12 intestinal fistulas. Pancreatitis occurred most often secondary to alcohol abuse, and fistula complicated controlled open drainage of the lesser sac more often than sump or Penrose drainage of the lesser sac. Fistulas appeared more often in patients with two or more drainage operations than in those with a single drainage procedure. Most duodenal fistulas closed with nonoperative therapy, whereas jejunal and colonic fistulas required operative closure. Operative techniques included both simple suture closure and resection with anastomosis. Five patients (29 percent) died. Thus, although frequent debridement and controlled open drainage may reduce the mortality rate of necrotizing pancreatitis, it appears to increase the likelihood of intestinal fistulas, which may require operative treatment. PMID- 2589595 TI - Significance of tumor spread in adenocarcinoma of the ampulla of Vater. AB - Twenty-eight patients with ampullary carcinoma were treated between 1965 and 1988: 22 underwent pancreaticoduodenectomy with 1 operative death (5 percent), 1 had local excision, 3 had bypass, and 2 were not explored. Of the 21 patients who survived pancreaticoduodenectomy, 4 had tumor confined to the ampulla, 7 had tumor extending into the duodenum, and 10 had tumor invasion beyond the duodenum. Nine of these patients had positive lymph nodes and 12 had negative lymph nodes. The patient who had local excision was disease-free at last follow-up 104 months postoperatively. Each of the three bypassed patients died of tumor progression within 15 months. The estimated 5-year survival rate for resected patients was 60 percent and was independently related to lymph node metastases (p = 0.031) and to tumor size (p = 0.039). This experience suggests that long-term survival is possible in patients with lymph node metastases or invasive tumors extending beyond the duodenal wall and that curative pancreaticoduodenectomy can be performed with a low operative mortality; therefore, aggressive surgical resection is recommended for all patients with ampullary carcinoma. PMID- 2589596 TI - Total gastrectomy in the treatment of advanced gastric cancer. AB - To assess the role of total gastrectomy in the treatment of advanced gastric cancer, we reviewed the records of 27 patients who underwent the procedure from 1979 to 1988. Operative mortality was 4 percent (1 of 27), and postoperative morbidity occurred in 48 percent of the patients. Twenty-five of 26 patients were tolerating solid food at the time of discharge; 21 were able to maintain oral alimentation until just prior to their death. Median survival following the operation was 15 months (range: 2 to 110 months), with a 62 percent absolute 1 year survival rate and a 38 percent 2-year survival rate. On the basis of these results, we conclude that in patients with advanced gastric carcinoma, total gastrectomy with Roux-Y esophagojejunostomy can be performed with an acceptable morbidity and mortality, provides significant palliation by restoring the patient's ability to eat, and should be performed when technically feasible, even in the presence of gross residual disease. PMID- 2589597 TI - Splenic abscess: presentation, treatment options, and results. AB - Pyogenic splenic abscess is a rare condition that tends to occur in patients with predisposing factors. The use of splenectomy or computed tomography-guided percutaneous drainage in 10 patients with splenic abscess is presented. In 8 of 10 cases, the diagnosis was based on abdominal computed tomography scan. Seven of 10 patients were treated with splenectomy, and 3 were managed with computed tomography-guided drainage. Abscess cultures included Escherichia coli, Enterobacter, Streptococcus viridans, Staphylococcus aureus, and Bacteroides fragilis. There were two morbidities and one death in the splenectomy group and no complications in those treated with percutaneous drainage. This review suggests a flexible approach in the management of splenic abscess. Although splenectomy remains the traditional treatment for bacterial splenic abscess, CT guided drainage may be appropriate in carefully selected patients. PMID- 2589599 TI - Management of empyema in children. AB - The antibiotic era has changed the incidence, causal factors, and gravity of empyema. Between 1977 and 1988, 27 children with empyema were surgically managed. Ten cases occurred after an operation (8 esophageal and 2 abdominal). There were 15 girls and 12 boys. The age range was newborn to 12 years. Symptoms included fever, cough, tube drainage postoperatively, anorexia, weight loss, chest pain, tachypnea, and lymphadenitis. Multiple aerobic and anaerobic organisms were cultured. Treatment included thoracentesis and antibiotics, tube thoracostomy, tube thoracostomy and bronchoscopy, decortication, or decortication with lobectomy. The total hospital stay averaged 28.3 days, and after decortication, 11.6 days. Empyemas in children frequently have multiple organisms and should be treated with broad-spectrum antibiotics while awaiting culture results. Thoracentesis and tube thoracostomy are often ineffective in curing the disease. Decortication can abbreviate hospital stay if performed promptly for persistent pleural sepsis. PMID- 2589598 TI - Inguinal herniation justifies sigmoidoscopy. AB - Controversy exists concerning the association of inguinal hernia and colonic carcinoma and, more specifically, whether the development of an inguinal hernia justifies sigmoidoscopy. To study the role of endoscopic screening in cases of inguinal hernia, we prospectively evaluated 464 patients with inguinal hernia over a 54-month period with flexible sigmoidoscopy. Each patient was over the age of 40 and male. Sigmoidoscopy documented polyps (97 patients, 21 percent) and carcinoma (22 patients, 5 percent). Multiple neoplasms were observed in 6 percent (7 of 119 patients). Occult blood was detected in the fecal specimens of 8 percent of the total group of patients, but in only 13 percent of the patients with polyps or carcinomas. A normal examination occurred in only 38 percent of the total group. By using the presence of an inguinal hernia in patients older than 40 years of age as an indication for sigmoidoscopy, we found that more than one of every four patients had an asymptomatic, concurrent malignant or premalignant colonic lesion. Flexible sigmoidoscopy should be used for screening colonic neoplasms in patients with inguinal hernia. PMID- 2589600 TI - An appropriate negative bronchoscopy rate in suspected foreign body aspiration. AB - Aspiration of foreign bodies in children can lead to illness and even death if not recognized and treated promptly. Seventy-six patients were referred to our hospital for suspected foreign body aspiration. The following is a retrospective review of their diagnosis and treatment. There was no foreign body found at bronchoscopy in seven patients (9 percent), and there were nine patients (12 percent) with bronchial foreign bodies who had a delay in diagnosis of foreign body aspiration. The delay averaged 35 days. These children, as a result of a prolonged period before diagnosis, were treated unnecessarily for pneumonia and asthma. Once correctly diagnosed, they had a significantly longer hospital stay. We propose that some negative bronchoscopies are necessary in order to prevent the morbidity that occurs from a missed foreign body aspiration. PMID- 2589601 TI - Evolution of synchronous renal and pancreatic transplantation. AB - The utilization of pancreatic transplantation as a therapeutic option in type I diabetics is dependent on demonstrating its safety and efficacy. A protocol for synchronous renal and segmental pancreatic transplantation, utilizing pancreaticocystostomy, was initiated in February 1985, and through December 1988, 44 patients (mean age 34.8 years) received dual allografts. At last follow-up, 25 patients had functioning kidneys, and 17 patients were insulin independent 4 to 50 months after transplantation, with a mean fasting blood glucose level of 86 mg/100 ml. As our experience increased, three factors were identified as reducing pancreatic allograft and patient survival: vascular thrombosis, inadequate control of pancreatic secretions, and coronary artery disease. As a result, our protocol was modified to include postoperative heparin, external stenting of the pancreaticocystostomy, and dipyridamole thallium testing to screen for coronary artery disease. With these modifications, technical failures and postoperative morbidity were reduced with a resultant increase in 6-month graft and patient survival. These results provide impetus for considering synchronous renal and pancreatic transplantation as a therapeutic option for type I diabetics with end stage renal disease. PMID- 2589603 TI - One more step? PMID- 2589602 TI - Algorithmically oriented update imaging in thyroid carcinoma. PMID- 2589604 TI - Atracurium recovery: prediction of safe reversal times with edrophonium. AB - The time to safe return of neuromuscular function after atracurium 0.3 mg/kg intravenously was assessed in 24 patients in whom anaesthesia was maintained with halothane 0.5%. Safe reversal (recovery to a T4 ratio greater than 0.5), after this dose of atracurium, could only be reliably and rapidly (less than 2 minutes) achieved with edrophonium if a period greater than 30 minutes elapsed since administration of the relaxant. This coincides with the appearance of four recognisable twitches if a train-of-four pattern of nerve stimulation is used. Thus, if no monitoring equipment is available, at least half-an-hour should elapse after administration of atracurium in a moderate dose (e.g. 0.3 mg/kg) before rapid and reliable reversal can be anticipated. Four twitches in a train of-four should be recognisable, if a nerve stimulator is available. PMID- 2589605 TI - Gastro-oesophageal reflux in pregnancy at term and after delivery. AB - Gastro-oesophageal reflux during a 40-minute reflux provocation test was assessed by lower oesophageal pH monitoring in 25 pregnant women at term, and again on about the second day after delivery. At term 17 women refluxed a total of 29 times; after delivery five women refluxed once each. There was a significant decrease in gastro-oesophageal reflux by the second day after delivery (p less than 0.05). Gastro-oesophageal reflux is, however, only one of the factors that predisposes to acid aspiration pneumonitis. PMID- 2589606 TI - The effects of secondary transport on critically ill patients. AB - This study examined the effect of secondary transport on critically ill patients and the effectiveness of a regionally based intensive care service. Four hundred and ninety-five patients were studied retrospectively over a 2-year period. Eighty-two were transferred from peripheral hospitals in a mobile intensive care unit while the remaining 413 were admitted directly to the intensive therapy unit at the Western Infirmary, Glasgow. The severity of illness in both groups was assessed using the APACHE II scoring system. The transferred group were scored before and after the journey, while the directly admitted group were scored only on admission. The results show that the transferred patients exhibited a consistent cardiorespiratory response to transport irrespective of their severity of illness, and that the mortality in both groups of patients in the intensive therapy unit was not significantly different. The results also suggest that in the transferred group, the outcome is not only dependent on the severity of illness but also on other factors, such as the hospital from which the patient was referred and the duration of the pretransfer admission. PMID- 2589607 TI - Spinal arteriovenous fistula. A possible cause of paraparesis after epidural anaesthesia. AB - A 62-year-old male suddenly developed a severe paraparesis after epidural anaesthesia. He recovered gradually over the next few months. He had an acute relapse one year later and a selective spinal angiography showed a dural T8 arteriovenous fistula with large draining veins. Intravascular embolisation of the fistula produced immediate and sustained clinical improvement. The mechanism commonly held responsible for neurological disturbances in spinal dural arteriovenous fistulas is cord hypoxia secondary to venous hypertension. The 20 ml of local anaesthetic solution injected into a narrow spinal canal with osteophytosis may have caused further venous engorgement, cord hypoxia and acute neurological deficit. PMID- 2589608 TI - Awake fibreoptic intubation for a rare cause of upper airway obstruction--an infected laryngocoele. AB - The anaesthetic management of a patient with an infected laryngocoele is presented. The relevance of this condition to the anaesthetist is discussed. PMID- 2589609 TI - Minitracheotomy--a life-threatening complication. AB - A 55-year-old patient developed profuse haemorrhage immediately after insertion of a minitracheotomy tube. Measured blood loss was 1.1 litres, and the bleeding required to be controlled surgically. The cause was a subglottic granuloma which had developed after prolonged tracheal intubation and which was incised during insertion of the minitracheotomy. PMID- 2589610 TI - The M1 air crash. The demands placed on anaesthetic and intensive care services of two hospitals. AB - The M1 air crash provided an enormous challenge to the anaesthetic and intensive care services of the hospitals which admitted the survivors, many of whom had serious injuries. This account describes some of the problems which were encountered in two of the hospitals, details the workload imposed on the anaesthetists and the staff of the Intensive Therapy Units and identifies factors which, if improved, might advance the management of multiple casualties admitted from the scene of a major disaster. PMID- 2589611 TI - Clinical and resource management: what are the options for anaesthetists? PMID- 2589613 TI - Is halothane obsolete? Two standards of judgement. PMID- 2589612 TI - Anaesthesia and the law. Respiratory failure in a young child after aspiration of hot tea. PMID- 2589614 TI - The management of hyponatraemia. PMID- 2589615 TI - The incidence of pruritus after epidural morphine. PMID- 2589616 TI - Overdose of ritodrine. PMID- 2589617 TI - Fentanyl overdose in a neonate: use of naloxone infusion. PMID- 2589618 TI - The costs of propofol in day surgery. PMID- 2589619 TI - A potential complication associated with a tracheal tube with a Murphy eye. PMID- 2589620 TI - Morbidity associated with antigravity suits. PMID- 2589621 TI - Pulse oximetry in mountain rescue and helicopter evacuation. PMID- 2589622 TI - An erroneous pulse oximeter reading. PMID- 2589623 TI - The high-risk register. PMID- 2589624 TI - Obstetric anaesthetic records. PMID- 2589625 TI - Mediastinal trauma--or not? PMID- 2589626 TI - When in doubt, take it out ... the epidural catheter. PMID- 2589627 TI - [Control of the ultrafiltration rate as the main component of a new balancing system in continuous hemofiltration]. AB - In 27 patients undergoing continuous pump-driven hemofiltration during intensive care, a new balancing device was used to control transmembrane pressure difference, and thus ultrafiltration rate, by means of an elastic reservoir and an infusion pump. The simultaneous infusion of substitution fluid by a second pump working independently of the former provided exactly and automatically the intended fluid balance. In only 0.7% of the total hemofiltration time (5519 h) could the preset ultrafiltration rate not be achieved. The simple components and installation of this device recommend its application in every intensive care unit that uses continuous arteriovenous or continuous pump-driven hemofiltration, relieving the staff and reducing unwanted and unnoticed deviations of intravascular volume and fluid balance. PMID- 2589628 TI - [Introduction of a new card for the "bedside test"]. AB - A new card for the obligatory ABO-group test is presented. There is sufficient space to perform the test by mixing patient and donor blood to the relevant antisera. As it does not offer any further information, testing for anti-AB has been deleted. Contaminated areas can easily be discarded afterward, minimizing any risk of infection. Only the documentation on the remaining portion of the card is legally important and needs to be entered into the patient's records. Choosing a new manufacturer has resulted in a very low price. PMID- 2589629 TI - [Quality assurance in North American anesthesia]. AB - To monitor the quality of care and identify opportunities to improve that care, the Department of Anesthesiology at Hutzel Hospital, Detroit (USA) has developed a quality assurance program. While the use of indicators represents the principal means of obtaining relevant quality of care information, there are several additional data sources that provide the departmental quality assurance committee with the necessary body of information to recognize problems in the delivery of anesthesia care and formulate indicated remedial actions. These can take the form of lectures, development of guidelines, or the acquisition of needed equipment. If identified problems are traceable to a specific practitioner, a number of interventional options are available to the chief of the department, ranging from individual counselling to recommending the removal of clinical privileges. The various corrective actions that have been instituted have led to improvements in clinical care, but perhaps of greater importance are the intangible changes in practice patterns that have occurred as a result of everyone's awareness that an effective monitoring process exists. PMID- 2589630 TI - [ECG-controlled placement of central venous catheters in patients with atrial fibrillation]. AB - Some workers state that sinus rhythm is essential for electrocardiographic placement of central venous catheters. We performed a prospective study to compare location control by ECG and by chest X-ray in 40 patients with absolute arrhythmia and atrial fibrillation. The criteria accepted as allowing the assumption of an intracardiac position of the catheter tip were: (1) Abrupt appearance of high-voltage P-waves when the right atrium (RA) was entered and their brisk disappearance when pulling the catheter back into the vena cava superior (VCS) and/or (2) a change in configuration and voltage of the QRS complex on withdrawal of the catheter from the right ventricle (RV). After establishment of an intracardiac position, the catheter was withdrawn until the ECG changed to show a trace identical to that seen before it had entered the heart. Then, in this study, the correct central venous position was confirmed by chest X-ray. The intravascular ECG revealed a correct placement of the catheter tip in the VCS in all patients but one. In this patient who had severe dysrhythmia, an intracardiac ECG could not be obtained, although the chest X-ray showed a correct position of the catheter in the VCS. While false-negative results (where an intracardiac catheter position cannot be documented although the catheter is in a central venous position) occasionally do occur, false positive results (with ECG suggesting an intracardiac location read, though the catheter tip is actually in a peripheral vein) are virtually impossible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589631 TI - [Preoperative autologous blood deposit and liquid storage for replacement arthroplasty]. AB - Transfusion of homologous blood components is associated with immunological (incompatibility, alloimmunization, immunosuppression) and infectious risks (hepatitis, cytomegalovirus, HIV and other agents). Endoprosthetic surgery of the hip and knee frequently requires transfusion. Preoperative deposit of autologous blood can reduce homologous transfusion requirements. The simplest method is liquid storage of whole blood. In order to re-examine the efficiency of our present scheme of preoperative deposit, we studied patients scheduled for endoprosthetic surgery with respect to the amount of blood deposited, stimulation of erythropoiesis, and homologous blood requirements at the time of operation. PATIENTS AND METHODS. Sixty-seven consecutive patients (33 men, 34 women) scheduled for endoprosthetic replacement of hip or knee or for revision arthroplasty of the hip were studied. Patients with anemia, coagulopathies, coronary heart disease, severe obstructive or restrictive pulmonary disease, cerebral sclerosis, syncopes and seizures were excluded from preoperative deposit. Patients deposited 450 ml at weekly intervals, with occasionally slightly higher or lower volumes. A patient was temporarily deferred when the hemoglobin concentration prior to donation fell below 11 g/dl. Blood was collected in CPDA-1 buffer. The aim was a deposit of three units. In patients undergoing exchange reoperation of a total hip arthroplasty, intra- and postoperative autotransfusion with a cell separator was employed in addition to preoperative donation. RESULTS. The age of the patients ranged from 43 to 83 years (mean +/- SD: 61.2 +/- 9.1). The differences between men and women with respect to height (172.9 +/- 6.8 vs 160.6 +/- 7.4 cm; p less than or equal to 0.001), weight (75.7 +/- 11.2 vs 69.1 +/- 11.0 kg; p less than or equal to 0.05), calculated blood volume (p less than or equal to 0.001), and erythrocyte volume prior to donation (p less than or equal to 0.001) were significant. A total of 185 units was deposited. Men donated 1350 (450-1970) ml blood (median, range) and women 1260 (340-1450) ml (p less than or equal to 0.01). Hemoglobin concentrations decreased significantly from an average of 14.7 g/dl in men and 13.8 g/dl in women prior to donation to 13.4 g/dl and 12.3 g/dl preoperatively (p less than or equal to 0.0001 for both groups). The donation was not associated with serious complications. For 4 patients the scheduled operation was deferred for a longer term. Forty-six patients (23 men, 23 women) underwent total hip arthroplasty, 12 (4 men, 8 women) exchange of total hip arthroplasty, and 5 (3 men, 2 women) endoprosthetic knee surgery. In total hip arthroplasty men required 0 to 500 ml homologous packed red cells (median=0), women 0 to 1250 ml (median=0;p less than or equal to 0.05). Thirty-nine (69.6%) of the patients, 19 (82.6%) men and 13 (56.5%) women, did not require homologous transfusion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2589632 TI - [Treatment of withdrawal symptoms using clonidine during pregnancy]. AB - In order to prevent symptoms of drug withdrawal during pregnancy, we treated a woman with clonidine, an alpha-2 adrenergic agonist with central and peripheral actions. We saw a good response of the withdrawal symptoms without any period of severe hypotension or bradycardia. Two healthy babies were subsequently delivered by cesarean section. PMID- 2589633 TI - The thalamus of the dog: a tridimensional and cytoarchitectonic study. AB - The organization of the thalamus varies considerably from species to species. This article reports a tridimensional study of the canine thalamus in which 18 nuclei were distinguished on the basis of their delimitation in sections and their differing cytoarchitectonic characteristics, the latter having been objectively quantified by means of an image analyser. On the basis of their location and/or mutual similarities, these 18 nuclei are classified in 5 groups. The thalamus of the dog is similar to that the cat, but differs considerably from those of other well-studied species. PMID- 2589634 TI - Topography and cytoarchitectonics of the nuclei of the posterior part of hypothalamus in insectivora. Part II. Regio premamillaris. AB - Cross-section paraffin scraps were stained with the methods of Nissl and Kluver Barrera. A description was given of the topography, shape and cell structure of the nuclei in the regio premamillaris in 3 insectivorous mammals: hedgehog, mole and common shrew. Attention was also given to the nervous centres located in the mentioned region but extending over the whole hypothalamus (nucleus perifornicalis, area hypothalamica lateralis). No differences were observed as to the location of the centres under study, but their cytoarchitectonics differed depending on the species. PMID- 2589635 TI - Anatomy of the pericallosal pial plexus in man. AB - Fine arterial branches on the superior surface of corpus callosum were investigated on 22 human brains under stereomicroscope. These branches were directed toward: 1. the upper surface of corpus callosum (3-6 branches, mean 8), 2. the depths of the sulcus corporis callosi (4-13 branches, mean 7), and 3. the cingulate gyrus (1-10 branches, mean 5). All the vessels composing the pericallosal pial plexus have a uniformed caliber of 0.9-0.6 mm at their origins, and 0.7-0.3 mm after branching. In 9 cases a longitudinal vessel within the stria longitudinalis medialis, connected with the pial plexus was found. Important details of morphology of this plexus and their significance are discussed. PMID- 2589637 TI - A stereologic study of the granule population of rat atrial myoendocrine cells: effects of chronic water/sodium restriction and acute water/sodium load. AB - The effects of chronic water/sodium restriction and acute water/sodium load on the "specific granule" population of rat atrial cardiocytes were investigated by stereology. The volume density (Vv) of atrial granules, which contain atrial natriuretic peptide (ANP), displayed a 135%-rise in water/sodium-restricted animals. The injection of 2.5 ml of isotonic saline to water/sodium-restricted rats provoked a striking degranulation of atrial myoendocrine cells (Vv of granules decreased by about 31%). The administration of an equal volume of hypertonic (5%) saline caused a more pronounced effect (Vv decreased by about 51%). These findings are in agreement with the view that chronic water/sodium restriction blocks the exocytotic release of atrial granules, without lowering the rate of their production. Moreover, they suggest that not only blood volume expansion, but also sodium ions can be a potent stimulating factor of ANP release. PMID- 2589636 TI - Developmental changes of the fore- and hind-limbs in the fetuses of the southern minke whale, Balaenoptera acutorostrata. AB - 15 fetuses of southern minke whale, Balaenoptera acutorostrata (from 8.2 mm C.R.L. to 38.9 mm C.R.L.), obtained from the Kyodo whale company in Japan (in whaling seasons from 1982 to 1986), were used for the present study. The fore limb first appears in the 11.4 mm fetus, and the hind-limb in the 15.3 mm fetus. The fore-limb develops progressively during gestation, while the hind-limb disappears by the 38.9 mm fetus. The critical period of limb development in southern minke whale was shown to be at a stage between that in the small sized species; Common Porpoise, Phocoena communis and Striped Dolphin, Prodelphinus caeruleoalbus, and in large one; Humpback Whale, Megaptera nodusa. PMID- 2589638 TI - A scanning electron microscope study of human pulp fibroblasts in culture. AB - Human pulp tissue was obtained from the first lower right molar of a 24 year old male patient during oral surgery. The tooth was healthy with no evidence of carious lesions. 6 cultures were initiated by the explant method. The cells were isolated and carried through 8 passages. Samples from different passages were fixed, dehydrated, and prepared for scanning electron microscopic observations. Some cells had a smooth surface, while others showed microvillous projections from their surface. Both cell types were seen in the same culture. However, in the third passage all the cells were of the smooth surface type. The cells were interconnected by a system of fibrils that were related to their surface. These fibrils also appeared to anchor the cells to the surface of the coverslips on which they were growing. This study showed that more than one cell type apparently existed in human pulp fibroblasts culture. Whether these cell types have different functional properties, or whether they are different developmental stages of the same cell type in culture, remain to be determined. PMID- 2589639 TI - [The effect of a modified blood supply on the craniofacial growth of the rabbit. 4. Skull and lower jaw asymmetry]. AB - Using a microscopic measuring method we were able to detect minor regions of asymmetry in the zygomatic arches of rabbits in which the common carotid artery had been ligated. These are considered in connection with the (also slight) asymmetric gains in the dry weight of the muscles of mastication in the ligated animals (see 2nd Bulletin). PMID- 2589640 TI - The pterygo-spinous muscle--an aberrant (atavic) remnant. AB - We report here on an aberrant pterygoid muscle found during a dissection of the infratemporal fossa. We have not noted such a muscle in hundreds of dissections in the area. A few anatomical texts (Piersol, 1911; Testut, Latarjet, 1931) have referred to its possible existence as the pterygo-spinous muscle. PMID- 2589641 TI - Localization of serotonin-like immunoreactivity in the Merkel cells of pig snout skin. AB - The presence of serotonin in the Merkel cells of pig snout epidermis was investigated by the peroxidase-antiperoxidase immunohistochemical technique. Serotonin-like immunoreactive Merkel cells were found in groups located at the base of epidermal rete pegs and in the external root sheath of sinus hair follicles (vibrissae). Immunoreactivity was stronger on the basal side of the Merkel cells, where dense-cored granules are most numerous. Neither the nerve terminal associated with the Merkel cell nor the neighbouring epidermal cells were immunostained. These results are the first evidence of serotonin-like immunoreactivity in mammalian Merkel cells. The fact that immunoreactivity is strongest in those parts of the Merkel cells with the highest granule density suggests that in these cells serotonin is probably localized in the dense-cored granules. PMID- 2589642 TI - Ultrastructural observation of the trans-Golgi associated plate-like cisterna in the secretory cells of the rat anterior pituitary gland with special reference to the intracisternal skeleton. AB - A well-developed plate-like cisterna (PLC) associated with trans-Golgi elements was observed in the Golgi apparatus of secretory cells in the rat anterior pituitary gland. This structure corresponds to the trans-most sacculotubular network. The PLC maintains a remarkably uniform thickness of about 33 nm, as measured between the outer leaflets of its unit membrane structure. As to the mechanism by which this peculiar construction of the PLC is maintained, pillar like structures were noted in the PLC intracisternal space, apparently acting as supports to keep the intermembrane distance constant. The PLC was especially well developed in hypertrophied cells such as gonadotrophs following castration. One noteworthy feature was that the PLC frequently ran parallel with the rough endoplasmic reticulum (RER), maintaining a constant distance from the latter in hypertrophied cells, but no membrane continuity between the PLC and RER was seen. PMID- 2589643 TI - Lymphatics and lymphoid tissue of the fallopian tube: immunoelectronmicroscopic study. AB - Lymphoid tissue of the human fallopian tube consists of follicles, lymphoepithelium, and lymphatic and blood capillaries and is located consistently in the interstitial part of the human fallopian tube. Using an immunoelectronmicroscopic technique, we have elucidated the ultrastructure of the lymphoid tissue of the human fallopian tube and the fine distribution and ultrastructure of the lymphatics associated with the rabbit fallopian tube. Lymphatic capillaries arise in the lamina propria mucosa and the periphery of follicles, where they are sparsely distributed, run through the muscular layer, and form a dense network in the subserosa. Characteristic features of the ultrastructure are aggregations of smooth muscle cells, alternating areas of densely and sparsely distributed collagen fibers, and unmyelinated nerve fibers beneath the lymphatic endothelium. Immunoelectronmicroscopic analysis has demonstrated an obvious difference in the distribution of T- and B-lymphocytes in the lymphoid tissue of the human fallopian tube. Many T-lymphocytes are present in the follicles and epithelium, but B-lymphocytes are either absent or rarely found. T-lymphocytes sometimes infiltrate into the basal lamina of the epithelium lying in close contact with the follicles. We conclude that the lymphoid tissue is constantly located in the interstitial part of the human fallopian tube and that intraepithelial lymphocytes, mainly T-lymphocytes, migrate via the basal lamina of the epithelium from follicles. Lymphatic capillaries in the fallopian tube may be the main migratory route of intraepithelial lymphocytes. The intraepithelial lymphocytes and epithelial cells of the fallopian tube have attracted considerable interest as a result of immunological studies of the recognition of spermatozoal antigens and the fertilized ovum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589644 TI - Cytodifferentiation of two epithelial populations of the respiratory bronchiole during fetal lung development in the rhesus monkey. AB - This study describes the cytodifferentiation of the two populations of epithelial cells found in the respiratory bronchiole of the adult rhesus monkey. One population, pseudostratified and containing ciliated, nonciliated secretory, and basal cells, is found overlying the pulmonary artery (PA). The other population, not associated with the PA, contains nonciliated cuboidal cells between alveolar outpockets. In this study we used terminal conducting airways from the lungs of fetal (90 to 155 days gestational age [DGA]), postnatal, and adult rhesus monkeys. Ciliated cells were partially differentiated at 90 DGA (54% gestation) and completely differentiated by 134 DGA (80% gestation). Nonciliated secretory cells were partially differentiated at 95 DGA (57% gestation) but did not lose all glycogen until the postnatal period. Basal cells appeared by 134 DGA (80% gestation) and matured in the postnatal period. Small mucous granule cells appeared at 125 DGA (74% gestation) and did not change throughout fetal development. Neuroendocrine cells were present throughout the entire period studied. Nonciliated cuboidal bronchiolar cells of the nonciliated population of the respiratory bronchiole appeared at 105 DGA (62% gestation) and matured in the postnatal period. We conclude that 1) although most of the differentiation of the lower airway occurs before birth, most of the cell types are not completely differentiated at birth; 2) the sequence of differentiation for the cells of the ciliated pseudostratified epithelial population is ciliated, nonciliated secretory, and basal; 3) the sequence of differentiation for the nonciliated secretory cell is similar to that of the secretory cells in more proximal airways; and 4) basal, neuroendocrine, and small mucous granule cells are not a part of the differentiation sequence of the other cell types. PMID- 2589645 TI - Effect of adriamycin on hamster molar tooth development in vitro: 1. Morphological changes. AB - The effect of adriamycin (1 mg/liter) on the development of the golden hamster 3 day-old second maxillary molars (M2) was investigated in vitro. Exposure of the molars to 1 mg/liter adriamycin during the first 2 hours of culture produced smaller teeth 3-7 days later, as determined by measurements of dry weights and by histological observations. Higher doses caused severe necrosis. The more differentiated pulp fibroblasts showed osteodentin formation 3 days after treatment with adriamycin (1 mg/liter), while the more immature ones underwent necrosis. The phenotypic changes brought on by the drug were permanent, and osteodentin continued to be formed throughout the course of this study. In addition the cervical loop region was inhibited from growing, while the production of the matrices of enamel and dentin appeared to be increased at 3 and 5 days after treatment. Electron microscopy of the forming osteodentin matrix revealed a random arrangement of banded collagen fibers during the early stage of osteodentin formation. As more matrix was formed, the collagen became quite compact and appeared quite similar to dentin. Finally, matrix vesicles were found among the collagenous matrix that was not yet mineralized. With the exception of the increased production of enamel and dentin, these in vitro results confirmed those earlier in vivo studies on the effect of adriamycin on rat incisor tooth. PMID- 2589646 TI - Differentiation of trophoblast of the baboon blastocyst. AB - The structure of trophoblast of the baboon blastocyst undergoes a number of maturational changes from the early blastocyst to the late blastocyst stage. The striking expansion of the blastocyst that occurs during the preimplantation period is accompanied by the development of an extensive endocytic apparatus. Cationized ferritin labels coated depressions and vesicles near the apical cell surface, numerous uncoated tubules and larger apical vesicles, and multivesicular bodies within trophoblast cells. Basally and laterally the labeled components are primarily small uncoated vesicles and tubules. Small, discrete clusters of ferritin particles were seen within the basolateral compartment between trophoblast and its basal lamina and beneath trophoblast cells that do not have a basal lamina. the results indicate that ingested materials may be directed in two pathways, one involving breakdown within the lysosomal system and one involving transcytosis. The zona pellucida is a trilaminar structure consisting of a fibrillar outer layer that often contains spermatozoa, an intermediate zone, and an inner layer containing columns of dense zonal material. Loss of the zona occurs after expansion of the blastocyst and development of the endocytic organelles. During the late blastocyst stage, syncytial trophoblast differentiates at the margin of the polar trophoblast. Because blastocysts were flushed from the uterus, it could not be determined whether azonal blastocysts had been adherent to the uterine surface prior to collection. PMID- 2589647 TI - Immunohistochemical evidence for the presence of neuropeptides in the hypothalamic suprachiasmatic nucleus of ground squirrels. AB - The cytoarchitecture and immunocytochemical distribution of neuropeptides (corticotropin-releasing factor, CRF; neuropeptide Y, NPY; oxytocin, OXY; vasopressin, VP; and vasoactive intestinal polypeptide, VIP) were studied in the hypothalamic suprachiasmatic nuclei (SCN) in male and female ground squirrels of two species (Spermophilus tridecemlineatus and S. richardsonii). Immunoreactive (IR) perikarya were found in sections incubated with VP or VIP antisera. VP-IR cell bodies were seen in the dorsal and medial parts of the nucleus in colchicine treated animals. IR fibers were distributed throughout the SCN. In the ventral part of the nucleus, VIP-IR cells were seen in untreated animals and were more pronounced in colchicine-treated animals. VIP-IR fibers and terminals form a dense plexus throughout the nucleus. Furthermore, NPY-IR terminals and fibers with multiple varicosities, but no IR perikarya, were present in the suprachiasmatic nuclei. Within the borders of the SCN, no cell bodies or fibers were stained with CRF or OXY antisera in any animal. PMID- 2589649 TI - Regional anesthesia for pediatric surgery. PMID- 2589648 TI - Embryonic development of the posterolateral structures of the knee. AB - The development of the structures in the posterolateral corner of the knee was studied in fifteen human embryos and seventeen fetuses by means of serial sections in the coronal and sagittal planes. The attachments of the lateral meniscus and fibular head to the popliteal tendon and muscle are formed during the process of cavitation that forms the bursa. The connection between the tendon and the posterior border of the lateral meniscus forms obliquely to follow the direction of the muscle and tendon. The edge of the bursa is limited by attachments that connect the tendon to the lateral meniscus and fibular head. In this study, no direct ligamentous continuity was found to exist between the posterolateral femur and tibia during development. The only ligament that indirectly connects the lateral femur posteriorly to the proximal segment of the tibia, which has never been reported in human development, is the one that links the popliteal tendon to the fibular head. We have designated this the popliteo fibular ligament which was also found in adult specimens. This ligament should not be confused with the arcuate popliteal ligament. PMID- 2589650 TI - Comparison of the fascia iliaca compartment block with the 3-in-1 block in children. AB - A new single injection procedure, the fascia iliaca compartment block, is described for blocking the femoral, lateral cutaneous, and obturator nerves. The technique consists of injecting a local anesthetic immediately behind the fascia iliaca at the union of the lateral with the two medial thirds of the inguinal ligament, and forcing it upward by finger compression. This block was prospectively evaluated in 60 pediatric patients aged 0.7 to 17 years undergoing surgery of the lower limb, and then compared with a similar group of 60 children given a 3-in-1 block. Adequate analgesia was only obtained in 20% of the patients given 3-in-1 blocks (group 1), whereas the fascia iliaca compartment block proved to be easy, free of complications, and effective in more than 90% of patients (group 2). Such a high failure rate in group 1 was not due to misplacement of the needle since a femoral nerve block developed in all patients. Therefore it is unlikely that the local anesthetic can spread rostrally towards the lumbar plexus then return peripherally along the issuing nerves, and this was, indeed, not confirmed by radiological findings. In the authors' opinion, a multieffective block can only develop when the local anesthetic is introduced behind the fascia iliaca, which circumscribes a potential space where the femoral, lateral cutaneous, and obturator nerves run for a considerable part of their course. This report shows that deliberately injecting this space almost always results in an easy and effective block of these three nerves. The fascia iliaca compartment block can be recommended for use in children. PMID- 2589651 TI - Effects of halothane on the conduction system of the heart in humans. AB - The effects of 2.0 MAC halothane on atrioventricular conduction times in humans were studied. A real-time recording system for the detection of surface His Purkinje potentials based on signal averaging techniques was used. Recordings were made in 23 patients before and after the administration of halothane. In 18 patients we were able to measure atrial (P-H) and His-Purkinje (H-V) conduction times (78%). A small but statistically significant decrease in P-H conduction times from 115.3 +/- 3.9 (SEM) to 110.8 +/- 4.2 ms was found (P less than or equal to 0.01). H-V conduction times did not change significantly. Heart rates decreased significantly from 87.6 +/- 2.6 to 74.8 +/- 2.5 beats/min (P less than or equal to 0.01). Systolic blood pressures decreased from 118.9 +/- 3.7 to 103.6 +/- 4.2 mm Hg. It is concluded that the decrease in heart rate and the decrease in atrial conduction time caused by halothane can be explained by interactions of several different mechanisms. The specific combination of slowing heart rate and a decrease of atrial conduction time provides a possible explanation for atrial arrhythmias during the administration of halothane. PMID- 2589652 TI - In vitro study on mechanisms of bupivacaine-induced depression of myocardial contractility. AB - Although several mechanisms have been proposed to explain bupivacaine cardiotoxicity, the predominant effect remains to be determined. In this study, we used an isolated rabbit right atrial model that reproduces the effects on inotropic and chronotropic functions induced by 0.5 micrograms/mL bupivacaine; then we tried to counteract these events by electrical stimulation or by addition of CaCl2 or adenosine triphosphate (ATP) to the bathing solution. Contractile force was dramatically depressed by bupivacaine alone (-68%), even when the preparation was paced (-59%). CaCl2 partially counteracted this decrease (-37%). Inotropic function was almost completely restored (-9%) when ATP was added before administration of bupivacaine. Inhibition of energy metabolism seems to be a major explanation for bupivacaine cardiotoxicity. PMID- 2589653 TI - Disposition kinetics of ropivacaine in humans. AB - The pharmacokinetic characteristics of a new local anesthetic drug, ropivacaine, were determined after intravenous infusion of 50 mg of the hydrochloride salt into six healthy male volunteers. Results showed that the disposition of ropivacaine can be described by a biexponential function. Its blood clearance (0.72 +/- 0.16 L/min) is intermediate between that of mepivacaine and bupivacaine. Plasma binding averaged 94% +/- 1% and the volume of distribution at steady state based on blood drug concentration was 59 +/- 7 L. The terminal elimination half-life was 111 +/- 62 min. PMID- 2589655 TI - Delayed side effects of droperidol after ambulatory general anesthesia. AB - The incidence of postoperative effects of droperidol, in the hospital and at home the following night, after general anesthesia for minor outpatient procedures was evaluated in two groups of 50 patients each. Anesthetic techniques were identical except for the presence or absence of 1.25 mg of IV droperidol. There were no differences between the groups with regard to postoperative nausea, vomiting, pain, or time to discharge. In 23% of patients given droperidol, anxiety or restlessness developed after discharge from the ambulatory care unit. No patient not receiving droperidol had these reactions. It is suggested that the routine use of droperidol in all outpatients receiving general anesthesia may not be appropriate. PMID- 2589654 TI - Motor and sensory blockade after epidural injection of mepivacaine, bupivacaine, and etidocaine--a double-blind study. AB - In a double-blind study of epidural anesthesia, 30 young volunteers were given either 2% mepivacaine (400 mg), 0.5% bupivacaine (100 mg), or 1.5% etidocaine (300 mg), all solutions containing epinephrine (1:200,000). The spread of analgesia was equal in the groups, whereas the longest duration was noted in the etidocaine and bupivacaine groups. With use of a method for determining muscle force, motor blockade during anesthesia was recorded quantitatively for hip flexion, knee extension, and plantar flexion of the big toe. Onset of motor blockade was significantly more rapid with etidocaine than with bupivacaine and mepivacaine. All subjects given etidocaine developed complete motor blockade, but with the other local anesthetics 5%-33% of the initial muscle force remained. The least motor blockade was found in the L5-S2 segment (plantar flexion of the big toe). The duration of maximal motor blockade varied between 60 min (mepivacaine) and 360 min (etidocaine). With each of the three local anesthetics, motor function returned simultaneously in the three muscle groups tested. Complete restoration of muscle function occurred significantly later for etidocaine (600 min) than for bupivacaine (360 min) and mepivacaine (180 min). With etidocaine, the motor blockade outlasted the sensory blockade by 150 min. The Bromage scale corresponded to the motor blockade only during the first half of the regression phase. Not until 1-3 h after attainment of Bromage grade 0 was the muscle force of all movements restored (90% of control values). PMID- 2589656 TI - Fentanyl inhibits the canine carotid chemoreceptor reflex. AB - To investigate the impact of fentanyl on the carotid chemoreceptor reflex, nine mongrel dogs were permanently monitored with electromagnetic flow transducers around the right common iliac artery and with heparin-filled catheters in the descending aorta and in one of the main carotid arteries with the tip just proximal to the carotid sinus. Carotid chemoreceptor activation (CCRA) produced by consecutive injections of nicotine (0.2-0.4 micrograms/kg) through the carotid catheter elicited bradycardia, expressed as an increase in cardiac cycle length by 140% +/- 18%, and a 252% +/- 16% increase in mean iliac arterial vascular resistance. These responses were markedly attenuated by fentanyl in a dose dependent fashion: cardiac cycle length increased only by 50% +/- 7% (P less than 0.01) with 4 micrograms/kg and by 19% +/- 6% (P less than 0.01) with 8 micrograms/kg of intravenous fentanyl. These changes were paralleled by significantly (P less than 0.01) lesser increases in mean iliac arterial resistance (122% +/- 9% and 50% +/- 5%). It is concluded that fentanyl impairs the integrity of the carotid chemoreceptor reflex. PMID- 2589657 TI - Preoperative anxiety: is it a predictable entity? AB - Most surgical and anesthesia personnel assume that certain factors lead to increased preoperative anxiety, yet the predictability of preoperative anxiety has not been extensively studied. We hypothesized that surgical and anesthesia personnel could be more effective in reducing preoperative anxiety if potential predictors of presurgical anxiety were identified. A sample of 523 patients awaiting elective surgery completed an anxiety scale, had their blood pressure and pulse measured, and had 14 different characteristics recorded. These characteristics included demographics, possibility of cancer, presence of support person, previous surgical experience, and extent of surgery. Female patients were more anxious than male patients, and individuals accompanied by a support person were more anxious than those not accompanied. However, all other factors were noncontributory to anxiety. It appears that patient anxiety does not reflect the assumptions of surgical and anesthesia personnel. This suggests that preoperative anxiety may reflect a patient's personality and coping style more than medical data. PMID- 2589658 TI - Orientation of fibers in human dorsal lumbar dura mater in relation to lumbar puncture. AB - Longitudinal insertion of a lumbar puncture needle bevel is less likely to cause post-lumbar puncture headache than is transverse insertion. The reason for this has not been entirely clear. We investigated the direction of dural fibers in posterior L3-4 dura mater obtained from three autopsies and tallied it in three orthogonal planes. Under low-power light microscopy the tissue appeared to be composed of lamellae branching irregularly and directed concentrically to the spinal cord. Electron micrographs (x5000) revealed that the lamellae consisted mainly of bundles of collagen fibers that pursued wavy courses in various directions. The lamellae also contained branching elastic fibers, many of which were directed longitudinally. This arrangement of fibers probably minimizes the tendency of a dural puncture hole to gape under tension if the needle bevel is directed longitudinally. PMID- 2589659 TI - Efficacy of oral cyclosporine given prior to liver transplantation. AB - The bioavailability of oral cyclosporine (CYS) dissolved in a large quantity of milk given just before liver transplantation (LTX) was evaluated in 30 patients, given randomly timed oral CYS before LTX, by measurements of CYS blood levels at induction, 2 h later, and at the time of graft reperfusion. Adequate blood CYS levels, defined as greater than or equal to 500 ng/mL (FPIA), could reliably be achieved only when the drug was administered 4 to 7 h preoperatively. Patients receiving the drug less than 4 h preoperatively generally had low levels thereafter (two of seven patients had greater than or equal to 500 ng/mL in any sample, compared with 13 of 14 patients in the 4-7-h group, P less than 0.011); an interval of greater than 7 h yielded unpredictable results. Fluids and blood products transfused, and preoperative ascites or ICU care, were not related to blood CYS levels. Oral CYS should be given 4 to 7 h before LTX to achieve adequate levels. PMID- 2589660 TI - Serum ammonia levels in response to glycine infusion in normal and cirrhotic rats. AB - Elevated serum ammonia may play a role in central nervous system derangement after transurethral resection of the prostate. Glycine used as a surgical irrigant for prostate resection produces ammonia as a by-product after liver and renal metabolism. The presence of liver dysfunction often leads to an inability to remove generated ammonia from the circulation. To determine whether the presence of cirrhosis allows significant metabolism of glycine and the resulting serum ammonia levels generated, the production of ammonia after glycine infusion was examined in normal and cirrhotic rats. Hepatic microsomal enzyme induction was produced in male Sprague-Dawley rats given sodium phenobarbital, added to the drinking water to hasten the development of cirrhosis, by increasing the toxicity of carbon tetrachloride given intragastrically to one group at weekly intervals for production of cirrhosis. A control group was maintained under similar conditions except for carbon tetrachloride dosing. The end point for production of cirrhosis was the development of ascites. Two weeks after the development of ascites in the cirrhotic rats and the discontinuation of phenobarbital in both groups, both control and cirrhotic rats were anesthetized with IP pentobarbital and glycine (1.25 g/kg; 7.5%) was given intravenously. Venous blood samples were taken at intervals up to 120 min for serum ammonia analysis. After the final serum ammonia sample, lethal pentobarbital injection was given and livers and kidneys removed for histologic analysis. Terminal body weight, glycine dose, and renal histology were not different between groups. Liver weights were greater in cirrhotic rats. Baseline serum ammonia levels were also greater int he cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589661 TI - Passive or active inspired gas humidification increases thermal steady-state temperatures in anesthetized infants. AB - We tested the hypothesis that active and passive airway humidification minimize hypothermia in infants, but that maintaining normothermia does not decrease the duration of postoperative recovery. A circle system was used to ventilate the lungs of anesthetized, intubated infants who were randomly assigned to active airway humidification and warming with use of an MR450 Servo airway heater and humidifier set at 37 degrees C (n = 10), passive airway humidification with use of the Humid-Vent Mini heat and moisture exchanger placed between the Y-piece of the circle and the endotracheal tube (n = 10), or no airway humidification and heating (control, n = 10). Anesthesia was induced with thiopental and maintained with isoflurane and nitrous oxide in oxygen. The relative humidity of inspired respiratory gases was approximately 35% in the control group and approximately 90% in the group undergoing active airway humidification. Initial inspired humidity in the passive humidification group (45%) increased to approximately 80% after 1 h of anesthesia. Humidity differed significantly across groups at all times (P less than or equal to 0.05). Steady-state rectal temperatures (100-120 min after induction) were 36.2 +/- 0.7 degrees C in patients given active humidification and heating, 35.7 +/- 0.9 degrees C in the passively humidified group, and 35.2 +/- 0.4 degrees C in the control group (P less than or equal to 0.05 between each group). Recovery from general anesthesia was rapid in all patients and did not correlate with central temperature changes or type of humidification (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589662 TI - What is the safest endotracheal tube for Nd-YAG laser surgery? A comparative study. AB - To determine whether a safe endotracheal tube for Nd-YAG surgery could be found, an Nd-YAG laser operating at 50 W was directed at six different endotracheal tubes that had 5 L/min of oxygen flowing through them. A plain Rusch red rubber endotracheal tube, a Bivona Fome-cuff laser endotracheal tube, a stainless steel Mallinckrodt Laser-Flex endotracheal tube, and a Xomed Laser-shield endotracheal tube were all ignited and perforated by the laser within 12 s. The combustion of the Mallinckrodt endotracheal tube can be explained by the high energy density of the laser that, in rapidly heating the metal, was able to cause its combustion in 100% oxygen. Red rubber endotracheal tubes wrapped with 3M No. 425 or Venture copper foil tape were unaffected by 1 min of exposure to the laser beam. They are recommended for clinical use. PMID- 2589664 TI - Marked sensitivity to pancuronium in a patient without clinical manifestations of myasthenia gravis. PMID- 2589663 TI - Effect of epinephrine on the duration of dibucaine (cinchocaine) spinal anesthesia. PMID- 2589665 TI - Isolated postoperative myoglobinuria in a pediatric outpatient. A case report of malignant hyperthermia. PMID- 2589666 TI - The Beelzebub nitrogen and preoxygenation. PMID- 2589667 TI - Pulse oximeters. PMID- 2589668 TI - Lumbar plexus blocks and lumbar plexus nerve blocks. PMID- 2589669 TI - Coronary artery vasospasm following placement of a cold liver graft during orthotopic liver transplantation. PMID- 2589670 TI - Inadvertent benzyl alcohol administration in neonates: do we contribute? PMID- 2589671 TI - A method of securing epidural catheters. PMID- 2589672 TI - Intravenous propofol during cesarean section: placental transfer, concentrations in breast milk, and neonatal effects. A preliminary study. AB - Placental transfer and neonatal effects of propofol were investigated in 21 women undergoing elective cesarean section under general anesthesia. This study was conducted in two separate phases according to the use of propofol. In both phases, anesthesia was induced with an iv bolus of 2.5 mg/kg of propofol. In phase 1 (n = 10), anesthesia was maintained with 50% nitrous oxide in oxygen and halothane. In phase 2 (n = 11), a continuous infusion of propofol at a rate of 5 mg.kg-1.h-1 was started after the induction dose. Maternal venous and umbilical cord arterial and venous samples were obtained at delivery. The propofol concentration in whole blood was measured with a high performance liquid chromatography method. Where possible, breast milk/colostrum was expressed for both phases postoperatively and a sample of blood was collected during phase 2 from neonates via a heel prick 2 h after birth. Propofol crossed the placenta, as demonstrated by concentrations found in umbilical venous blood in phase 1 (0.13 0.75 micrograms/ml) and in phase 2 (0.78-1.37 micrograms/ml). At delivery, the ratio of the drug concentration in umbilical venous blood to that in maternal blood was 0.70 +/- 0.06 for phase 1 and 0.76 +/- 0.10 for phase 2. The ratio of propofol concentration in the umbilical artery to that in the umbilical vein was 1.09 +/- 0.04 for phase 1 and 0.70 +/- 0.05 for phase 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589673 TI - Subarachnoid injection--a potential complication of retrobulbar block. AB - This study was undertaken to illustrate the potential for subarachnoid injection during retrobulbar block as a cause of respiratory arrest. Cadaver orbits were used to document the connection between the optic nerve sheath and the subarachnoid space. Following dissections of the orbits on one side of 24 cadavers, the optic nerve sheaths were identified and injected with 0.5 ml of water for measurement of pressure generated during injection. This was followed by intrasheath injection of equal volume of methylene blue for demonstrating the subarachnoid space surrounding the optic nerves. All injections were performed with a 1-ml syringe with a one-and-one-half-inch 22-G needle over a period of 10 s. The blue dye was found to track along the subarachnoid space of the optic nerve sheath to the chiasmatic cistern in the middle cranial fossa. Retrobulbar injections were performed on the contralateral undissected orbits and intrascleral injections were performed on undissected eyes. The size of the syringes, the gauge of the needles, and the speed of injection were uniform for all injections. The pressure generated by injection into the optic nerve sheath or intrascleral injection (approximately 138 mmHg) was three- to fourfold that produced by injection into the retrobulbar adipose tissue (approximately 35 mmHg) (P less than 0.05). The authors conclude that any resistance encountered during retrobulbar block should serve as a warning signal, mandating redirection of the needle, in order to prevent subarachnoid injection. PMID- 2589674 TI - Air: an effective indicator of intravenously located epidural catheters. AB - The authors conducted a two-part study to evaluate the efficacy of 1 ml of air as a "test dose" for detection of intravenously located epidural catheters. In part 1, a Doppler fetal heart rate monitoring probe was placed over the precordium of 33 laboring patients in whom functioning epidural catheters were in place. Each patient received, more than 90 s apart, in random order: 10 ml of agitated saline (containing less than 0.5 ml of air microbubbles) via a peripheral vein; 2 ml of air via the epidural catheter; and a sham injection (i.e., nothing injected). In all 33 cases, a blinded observer identified Doppler changes 10-30 s following the injection of air (microbubbles) via peripheral vein. Doppler changes were never heard following epidural air injection (P less than 0.001 compared with iv air microbubble injection) or the sham injection (P less than 0.001 compared with iv air microbubble injection). In part 2, the authors listened for Doppler heart tone changes while injecting 1 ml of air via catheters that were accidentally inserted in the epidural veins of five other patients. Unequivocal Doppler changes compatible with intracardiac air always occurred within 3 s, and no signs or symptoms of air embolism developed. The results suggest that 1 ml of air may be a suitable indicator of iv epidural catheter location. PMID- 2589675 TI - Ancrod (Arvin) as an alternative to heparin anticoagulation for cardiopulmonary bypass. AB - Heparin is the anticoagulant used during cardiopulmonary bypass (CPB). Both the use of heparin and the reversal of its effect with protamine have well-documented complications. Ancrod is a defibrinogenating enzyme that has been used as an anticoagulant in humans, but its use as an anticoagulant for CPB has been limited to studies in animals. Twenty patients for elective aortocoronary bypass surgery were anticoagulated by means of an intravenous infusion of ancrod pre operatively. Target plasma fibrinogen concentrations of 0.40-0.80 g/l were achieved within 13.3 +/- 2.5 h using an average dose of ancrod of 1.65 +/- 0.55 U/g. All perfusions were without incident. Postoperative blood loss (2286 +/- 1311 cc) was compared to that of 20 matched controls (1737 +/- 973 cc), as was blood product use; 4.1 +/- 2.1 U of packed cells versus 2.5 +/- 2.3 U (P less than 0.05) and 5.6 +/- 3.1 U of plasma versus 2.6 +/- 2.9 U (P less than 0.05) in the ancrod and heparin-treated groups, respectively. There were no differences in the postoperative courses or recovery periods of the ancrod-treated and control patients. This study confirms the efficacy and feasibility of ancrod as an alternative form of anticoagulation for CPB. PMID- 2589676 TI - Age and gender influence halothane-associated hepatotoxicity in strain 13 guinea pigs. AB - The factors of age and gender, which have been linked to development of fulminant halothane hepatitis in humans, were evaluated in a guinea pig model of acute halothane-associated hepatotoxicity. Since nitrous oxide is commonly coadministered with halothane and has been shown to exacerbate halothane associated liver injury in rats; this combination of anesthetics was also evaluated in guinea pigs. Male and female strain 13 guinea pigs (300-1000 g) were exposed to 1% v/v halothane and 39% O2 for 4 h with a balance of either 60% N2 or 60% N2O. Both animal age, as determined by body weight, and gender proved to be factors in the model with older (approximately 6.2 +/- 1.0 month) guinea pigs of both sexes, demonstrating significantly greater elevations in plasma ALT and a greater incidence of centilobular necrosis versus younger (approximately 3.1 +/- 0.6 month) animals. Older females showed a greater hepatotoxic response than older males. There were no significant differences in halothane plasma metabolite levels between older and younger animals of either gender. The addition of nitrous oxide affected neither plasma concentrations of halothane metabolites nor the degree of resultant hepatic injury. Older (approximately 5-6 month) male guinea pigs, from a strain (inbred Hartley) previously shown to be resistant to the halothane lesion, did not develop centrilobular necrosis following halothane exposure even though they generated plasma metabolite concentrations equivalent to those generated by strain 13 animals. The lack of differences in the biotransformation of halothane between groups indicates that other intrinsic factors must be involved in the observed variations in susceptibility to hepatic injury. PMID- 2589677 TI - Adverse effects of halothane in a canine model of acute right ventricular hypertension. AB - The effects of acute right ventricular (RV) hypertension (RVH) induced by pulmonary artery (PA) constriction, and of two concentrations (mean inspired 0.8 and 1.5%) of halothane (HAL) during RVH on global and regional RV performance (ultrasonic dimension technique), and on coronary hemodynamics (electromagnetic flow probes) were studied in 12 open-chest dogs anesthetized and paralyzed by continuous infusions of fentanyl and pancuronium. Following PA constriction, RV systolic pressure more than doubled, RV end-diastolic and systolic dimensions increased, and stroke volume (SV) and segment shortening fell (P all less than 0.05). There was no evidence of regional myocardial dysfunction (i.e., akinesis, systolic lengthening, postsystolic shortening), and reactive hyperemia in response to right coronary artery occlusion was present. Subsequent addition of HAL (0.8%) resulted in further increases in end-diastolic and systolic dimensions, and in marked decreases in right coronary blood flow, segment shortening, SV, and aortic pressure. During HAL 1.5% (range: 1.2-1.6%), regional myocardial dysfunction developed in three animals, reactive hyperemia was abolished in five out of six animals tested, and metabolic acidosis developed. Release of PA constriction during 1.5% HAL in seven animals resulted in improved global and regional RV performance, disappearance of regional myocardial dysfunction, and restoration of reactive hyperemia. In this canine model of acute RVH, increasing concentrations of HAL led to increasing deterioration in global and regional RV performance most likely due to inadequate coronary perfusion. PMID- 2589678 TI - Experimental analysis of catheter-manometer systems in vitro and in vivo. AB - The static and dynamic responses of two combinations of transducer amplifiers, pressure transducers, resonance elimination devices, extension tubing, and transcutaneous cannulae were tested in vitro using a sine-wave pressure generator, and in vivo by square-wave pressures generated by a "fast-flush" device. In addition, carotid arterial blood pressure waveforms recorded by these systems in sheep, at two different heart rates, were compared with those simultaneously recorded with a catheter-tip pressure transducer. A new term, "Working Heart Rate" is defined and allows for the prediction of the maximum heart rate up to which a system of given frequency response and damping coefficient should be accurate. When tested in vitro, all the monitoring systems were underdamped and resonated. The performance of all systems was improved by inclusion of an adjustable resonance elimination device but impaired by a nonadjustable resonance eliminator or by recording with an electronically filtered amplifier. When tested in vivo, the accuracy of mean and diastolic blood pressure measurement was not affected by any combination of heart rate, amplifier, length of extension tubing, or use of resonance eliminators. Both resonance elimination devices improved the performance of all systems. In contrast to predictions based on frequency response and damping, the smallest errors in systolic blood pressure were recorded using the electronic filter or the nonadjustable resonance eliminator. There were considerable and misleading differences between the frequency responses and damping coefficients calculated in vitro and those, for the same systems, derived from the in vivo fast-flush tests. It is concluded that the most accurate and consistent readings of systolic blood pressure will be achieved with the use of either an electronic filter or a nonadjustable resonance eliminator. PMID- 2589679 TI - The effects of magnesium salts on the duration of epinephrine-induced ventricular tachyarrhythmias in anesthetized rats. AB - The effects of MgSO4 or MgCl2 infusion on the duration of epinephrine-induced cardiac arrhythmia were evaluated in male rats anesthetized with either halothane or pentobarbital. In addition, the duration of epinephrine-induced arrhythmia in pentobarbital (50 mg/kg) anesthetized rats was compared with the duration of arrhythmia in halothane (1.5%) anesthetized rats. During halothane anesthesia MgSO4 or MgCl2 infused at a dose rate of 8 mg.kg-1.min-1 for 20 min caused a significant reduction in the duration of arrhythmia (100% and 80%, respectively) following a 4-microgram/kg injection of epinephrine and a significant threefold reduction in arrhythmia duration for each salt following an 8- or 16 micrograms/kg injection of epinephrine. Significantly shorter periods of arrhythmia after each dose of epinephrine were seen in rats anesthetized with pentobarbital than were seen in rats anesthetized with halothane. No significant difference was seen between MgSO4 or MgCl2 infusions in any of these studies. Twenty-minute infusions of MgSO4 (8 mg.kg-1.min-1) were compared with propranolol (0.03 mg.kg-1.min-1) and verapamil (0.5 micrograms.kg-1.min-1) infusions on the duration of arrhythmia after epinephrine (8 micrograms/kg) injections in halothane anesthetized rats. MgSO4 and propranolol infusion caused a significant reduction in the duration of arrhythmia (81% and 70%, respectively). Verapamil infusion caused only a 48% reduction in arrhythmia duration. While there was no significant difference between MgSO4 or propranolol, both caused a significantly greater reduction in arrhythmia than verapamil. CaCl2 (0.15 mM.kg-1.min-1) infusion for 5 min caused a significant fivefold increase in the duration of arrhythmia during halothane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589680 TI - Myocardial sensitization by thiopental to arrhythmogenic action of epinephrine in dogs. AB - This study examined the interaction between thiopental and epinephrine in inducing ventricular arrhythmias in dogs. The arrhythmogenic threshold of epinephrine was determined during anesthesia with either halothane alone, thiopental alone, etomidate plus different doses of thiopental, or halothane plus different doses of thiopental. The arrhythmogenic dose and the corresponding plasma concentration of epinephrine during thiopental anesthesia (plasma thiopental concentration: 46-57 micrograms/ml) were 0.77 +/- 0.04 micrograms.kg 1.min-1 and 10.7 +/- 1.5 ng/ml, respectively. During halothane anesthesia (end tidal: 1.3 MAC) they were 2.59 +/- 0.49 micrograms.kg-1.min-1 and 45.3 +/- 9.2 ng/ml, respectively. The dose-effect relationship for the thiopental action was examined during etomidate plus thiopental and halothane plus thiopental anesthesia. The arrhythmogenic plasma concentration of epinephrine was inversely proportional to the plasma thiopental concentration during both anesthetics. During etomidate plus thiopental anesthesia, at plasma thiopental concentrations of 0, 11.2 +/- 0.83, 20.1 +/- 1.34, and 33.2 +/- 1.95 micrograms/ml, the corresponding epinephrine concentrations were 201.3 +/- 34.3, 142 +/- 19.5, 69.1 +/- 21.2, and 22.7 +/- 4.5 ng/ml. During halothane plus thiopental anesthesia, at plasma thiopental concentrations of 0, 10 +/- 0.86, 18.3 +/- 0.87, and 31.8 +/- 1.05 micrograms/ml, the corresponding epinephrine concentrations were 45.3 +/- 9.2, 34.6 +/- 8.9, 16.2 +/- 1.74, and 15.1 +/- 1.32 micrograms/ml, respectively. These results suggest that thiopental sensitizes the heart to epinephrine in a dose-dependent manner. This sensitizing action of thiopental would in part explain the thiopental potentiation of hydrocarbon anesthetic-epinephrine arrhythmias. PMID- 2589681 TI - Ventilatory effects of fourth cerebroventricular infusions of morphine-6- or morphine-3-glucuronide in the awake dog. AB - The ventilatory effects of morphine-6-glucuronide (M-6-G) and morphine-3 glucuronide (M-3-G) were evaluated in awake dogs (n = 10). A fourth ventricle to cisterna magna perfusion (VCP) system was used for drug administration. This permitted a direct comparison of the dose/ventilatory response characteristics of these morphine metabolites to each other and to morphine and obviated the need to consider the blood-brain barrier delay that would complicate analysis of systemic dose versus ventilatory response relationships among these drugs. The dose/response pattern for morphine was taken from an earlier study in unanesthetized dogs where the identical mode of drug delivery as in the present report was employed. Morphine-3-glucuronide caused, if anything, a ventilatory stimulation (decreased PaCO2 and increased CO2 responsiveness) at the highest infusate concentration studied (50 micrograms/ml) and no significant ventilatory effects at infusate concentrations at or below 10 micrograms/ml. On the other hand, M-6-G produced a profound dose-dependent ventilatory depression. Significant increases in PaCO2 and diminution of CO2 responsiveness were observed even at the lowest infusate concentration evaluated (0.1 microgram/ml). When compared to morphine, M-6-G was found to be about five to ten times more potent as a ventilatory depressant drug. These results imply that M-6-G may play a significant role in the ventilatory depression accompanying systemic morphine administration. PMID- 2589682 TI - Electrophysiologic assessment of the effects of enflurane, halothane, and isoflurane on properties affecting supraventricular re-entry in chronically instrumented dogs. AB - Most paroxysmal forms of clinical supraventricular tachycardia (SVT) are likely due to re-entrant excitation. Electrophysiologically demonstrated mechanisms for re-entrant SVT include, in descending order of importance, atrioventricular (AV) node, AV node and accessory (AV bypass) pathway, sinus node, or atrial re-entry. Except for sinus node re-entry, none of these mechanisms for re-entrant SVT can be reliably reproduced in animal models. The authors suspected, however, that anesthetic effects on atrial and AV nodal electrophysiologic properties might be used to predict their actions against suspected re-entrant SVT. Awake-to anesthetized (1.2 and 1.6 MAC) comparisons for the effects of enflurane (ENF), halothane (HAL), and isoflurane (ISO) on atrial and AV nodal electrophysiologic properties were made in ten chronically instrumented dogs. Studies were carried out with and without pharmacologic autonomic blockade with atropine, propranolol, and hexamethonium. By ANOVA, significant (P less than 0.05) effects of the anesthetics included: prolongation of AV nodal conduction time and the Wenckebach point in dogs with autonomic blockade (ENF, HAL, ISO); increased atrial effective and functional refractory periods in dogs without autonomic blockade (ENF, ISO); increased atrial functional refractory period in dogs without autonomic blockade (HAL); increased AV nodal functional refractory period in dogs with and without autonomic blockade (ENF, ISO), or with autonomic blockade (HAL). Sinus node re entry, manifest by atrial echo beats during high right atrial stimulation, could be demonstrated in several dogs of each anesthetic test group during awake electrophysiologic testing. All anesthetics, with or without autonomic blockade and autonomic blockade in awake dogs, invariably abolished such re-entry. It is concluded that any anesthetic that increases atrial and AV nodal refractoriness should not be conducive to SVT caused by AV node or atrial re-entry. All of the anesthetics tested also appear effective against sinus node re-entry in dogs in which this mechanism can be demonstrated. Finally, no conclusions can be reached concerning anesthetic effects on re-entry requiring participation of both AV node and AV bypass pathways, since anesthetic effects on AV bypass pathways were not tested. PMID- 2589683 TI - Effects of epidural anesthesia on cardiovascular response and survival in experimental hemorrhagic shock in dogs. AB - The purpose of the present study was to assess the effects of epidural anesthesia on cardiovascular responses and survival in experimental hemorrhagic shock in dogs. Thirty mongrel dogs were randomly assigned to one of three groups on the basis of anesthetic technique: the upper-level group (n = 10), receiving general anesthesia plus upper-level (mainly thoracic region) epidural anesthesia; the lower-level group (n = 10), receiving general anesthesia plus lower-level (mainly lumbar region) epidural anesthesia; and the control group (n = 10), receiving general anesthesia alone. After withdrawal of blood, the changes in mean arterial pressure (40 mmHg) and cardiac index were similar in all groups. In the upper level group, a lower heart rate and systemic vascular resistance than the control group were maintained throughout in the presence of severe hypotension. A significant difference in survival was seen between the upper-level and control groups over the 100-min observation period as a whole (P less than 0.05 by the Generalized Wilcoxon test), since, at the end of the period, only two of the ten animals in the control group survived, whereas nine of ten in the upper-level group survived (P less than 0.001 by the Kaplan-Meier test). This result demonstrates that, in dogs lightly anesthetized with halothane and nitrous oxide, upper thoracic level epidural anesthesia significantly improves survival in experimental hemorrhagic shock (compared with survival in dogs with lumbar epidural or no epidural anesthesia) when the epidural is performed before hemorrhage and when the mean arterial pressure is constant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589684 TI - Inspiratory work and response times of a modified pediatric volume ventilator during synchronized intermittent mandatory ventilation and pressure support ventilation. AB - Volume ventilation by demand flow ventilators significantly increases work of breathing during inspiration. Although various ventilator modifications and different modes of ventilation have been developed, there have been few studies regarding imposed work of breathing in infants and children. This study was designed to evaluate several modifications of a commercially available demand flow ventilator designed to shorten response time (tr) and decrease the imposed work (Wi) involved in opening the demand valve. Minimum withdrawal volume (Vmin), maximum negative pressure (P mneg), and tr were measured. Wi was defined as the product of Vmin and P mneg. Seven Siemens Servo 900C ventilators were tested under 16 different trial conditions with four variables: 1) mode of ventilation (synchronized intermittent mandatory ventilation [SIMV] vs. pressure support ventilation [PSV]); 2) caliber of circuit tubing (adult vs. pediatric); 3) location of airway pressure monitor (distal vs. proximal); and 4) ventilator trigger sensitivity (0 cm H2O--high vs. -2 cm H2O--low). Vmin, Pmneg, and Wi were all decreased (P less than .05) while tr was unaffected by changing ventilator trigger sensitivity from low to high. Wi was decreased by pediatric tubing and proximal airway pressure monitoring only when low trigger sensitivity was used. PSV and proximal airway monitoring shortened tr. The authors conclude that the use of pediatric circuit tubing and proximal airway pressure monitoring with a Siemens Servo 900C ventilator significantly improved ventilator performance. PMID- 2589685 TI - Asymptomatic cardiomyopathy presenting as cardiac arrest in the Day Surgical Unit. PMID- 2589686 TI - Prolonged relief of acute postamputation phantom limb pain with intrathecal fentanyl and epidural morphine. PMID- 2589687 TI - Effects of nitrous oxide on rat embryos grown in culture. PMID- 2589688 TI - The measurement of expired oxygen as disconnection alarm. PMID- 2589689 TI - Macroglossia causing airway obstruction following cleft palate repair. PMID- 2589690 TI - Proper lateralization of left-sided double-lumen tubes. PMID- 2589691 TI - Failure of a nitrous oxide-oxygen proportioning device. PMID- 2589692 TI - One more use of a vinyl glove: ready-made protection for the reusable pulse oximeter monitoring probe. PMID- 2589693 TI - An orthogonal ARMA identifier with automatic order estimation for biological modeling. AB - In this paper an ARMA identification algorithm is developed for modeling biological time series data. The algorithm is based on Gram-Schmidt orthogonalization of automatically selected basis functions from a specified function space. The selection criterion is based on recursive testing of potential benefit to the model of candidate functions. The candidate functions, AR and MA terms, are tested in a pair-wise search direction until a least-squares criterion is satisfied, thereby estimating the order. Additive noise is considered and the basic algorithm extended to improve performance in noise. The algorithm is also extended to systems with inaccessible inputs (signal modeling). Modeling of biological data from speech is included, and indicates good performance. The algorithm is derived from earlier work on nonlinear systems identification. PMID- 2589694 TI - A dynamic nonlinear lumped parameter model for skeletal muscle circulation. AB - A dynamic nonlinear lumped parameter model of the circulation of skeletal muscle for constant vasoactive state is presented. This model consists of four compartments that represent the large arteries, the arterioles, the capillaries and venules, and the veins, respectively. The first compartment consists of a linear compliance (C1) and resistance (R1). The third compartment possesses no compliance and is represented by a linear resistance (R3). The second and fourth compartments each consist of a nonlinear pressure-volume relation, resulting in a pressure dependent compliance (C2, C4, respectively) and nonlinear resistance (R2, R4, respectively). The eleven model parameters were collected in a complementary way: they were partly obtained from a priori knowledge including information at the microscopic level, and partly determined by means of an estimation algorithm. Estimated values of the compliances (in cm3.kPa-1.100 g-1, 1 kPa = 7.5 mmHg) and resistances (in kPa.s.cm-3.100 g) at an (arterial) inflow pressure of 10 kPa and a (venous) outflow pressure of 0 kPa were: C1: 0.014; R1: 6.6; C2: 0.565; R2: 84.6; R3: 37.9; C4: 1.044; R4: 24.5. The model (with the nonlinear pressure-volume relations) is able to predict the static and dynamic instantaneous (i.e., for constant vasomotor tone) pressure-flow relation and the instantaneous zero flow pressure intercept. These phenomena are therefore not necessarily the result of the rheological properties of blood. The secondary or delayed dilatation upon a positive inflow pressure step (or negative step in venous pressure) is predicted by the model implying that delayed dilatation is not necessarily related to changes in vasomotor tone. Venous outflow delay, upon a positive inflow pressure step (starting from zero flow), is also predicted by the model. PMID- 2589696 TI - Correcting for the thermodynamic characteristics of a body plethysmograph. AB - A constant volume body plethysmograph is used to measure changes in total body volume by relating pressure changes measured inside a closed chamber to changes in its volume. The relationship between pressure and volume, however, is complicated by the fact that rapid changes in pressure are accompanied by changes in the temperature of the gas in the plethysmograph. The rate at which the temperature of the gas subsequently approaches that of the environment affects the frequency response of the plethysmograph as a volume measuring instrument. In this paper it is shown that the transient response in plethysmograph pressure to a step change in volume must be a multi-component function, due to the gas near the walls of the plethysmograph approaching thermal equilibrium with the environment at a faster rate than gas near the center. The step response of a 200 L plethysmograph was determined experimentally and found to be well described empirically by a sum of two decaying exponential functions of time. The fitted exponentials were used to construct an algorithm for digitally correcting a measured pressure signal for the effects of the plethysmograph response. When applied to a hypothetical volume waveform over a single breath, an almost perfect correction was obtained. PMID- 2589695 TI - Simulation of airway closure during forced vital capacity. AB - Airway closure, which disconnects peripheral respiratory units from the trachea, has been observed during expiration to residual volume. It is attributed to dynamic compression that may cause unstable collapse and closure of small airways. During forced vital maneuvers, airway closure is expected to be more significant owing to the maximum expiratory effort. In the present study we have added a simulation of airway closure to the model developed by Elad and associates which simulated flow limitation during forced expiration. Progressive closure is simulated by variation in the number of branches and their cross sectional areas rather than by change in tube law. The results demonstrate that peripheral airway closure may explain the reduction in maximal flow rate at small lung volumes. It can reproduce either the abrupt fall in maximal expiratory flow volume curves as observed in dog lungs or the gradual decrease that has been observed in humans. PMID- 2589698 TI - Proceedings of the SAEM-IRIEM research symposium and the ACEP winter symposium. Fort Lauderdale, Florida, February 1989 and Tampa, Florida, March 1989. PMID- 2589697 TI - Central venous blood temperature fluctuations and thermodilution signal processing in dogs. AB - Pulmonary artery blood temperature fluctuations are a principle source of variability of thermodilution cardiac output measurements. Two signal processing strategies were investigated to decrease this variability; a subtractive noise cancellation algorithm, developed from a heat balance model of heat transport through the right heart, and a band pass integration technique. Blood temperature fluctuations were recorded from the inferior and superior vena cavae and the pulmonary artery in four dogs. The recorded temperature signals were processed off line to investigate the performance of the signal processing strategies. The findings indicate that the accuracy of the heat transport model, while dependent on the accuracy of the sensing of caval blood temperature, is sufficient for cancellation of a significant fraction of the pulmonary artery thermal noise power if the amplitude of the fluctuations is large. The use of the subtractive cancellation algorithm improved the standard deviation of thermodilution curve area determinations by a factor of five, relative to area estimates made without noise cancellation. Band pass integration produced a more modest improvement in area estimate reproducibility. These results demonstrate that it is possible to reduce, but not eliminate, the variability of thermodilution cardiac output measurements with the described processing strategies. PMID- 2589699 TI - Development of a decision algorithm for a semiautomatic defibrillator. AB - A decision algorithm was developed for a semiautomatic defibrillator. The function of the algorithm is to evaluate the ECG of a patient and determine whether a defibrillation shock should be delivered. The development process included establishment of defibrillation criteria, creation of ECG databases, algorithm design, development of test protocols, and clinical testing. The result was an algorithm with sensitivity and specificity sufficiently accurate to allow a defibrillation shock to be delivered safely outside the hospital. PMID- 2589700 TI - Blunt trauma to the abdomen. AB - There is general agreement that physical examination alone is inadequate for abdominal evaluation in the multiply injured blunt trauma patient; but controversy exists regarding the preferred method of detecting intraabdominal injuries requiring celiotomy. Both peritoneal lavage and the newer computed tomography imaging techniques have advantages and disadvantages. Direct comparisons of the two techniques have not determined a preferred method. When used as complementary rather than competitive studies, diagnostic peritoneal lavage and computed tomography imaging provide more information than either test alone. PMID- 2589701 TI - Blunt rupture of the diaphragm: mechanism, diagnosis, and treatment. AB - In the absence of respiratory distress and massive visceral herniation, the diagnosis of blunt diaphragmatic disruption can be difficult. This is particularly true for diaphragmatic injuries confined to the right hemidiaphragm. Because diagnostic delay and strangulation are associated with notable increases in mortality and morbidity, it is important to identify the injury as early as possible. Victims of lateral impact motor vehicle collisions are more likely to experience rupture of the diaphragm than victims of frontal collisions. Occupants exposed to left lateral impacts are at greatest risk. The side of diaphragmatic rupture correlates with the direction of impact. The right hemidiaphragm is more resistant to rupture. Deformation shear is a more plausible mechanism for diaphragmatic rupture after lateral impacts. Knowledge of the mechanisms that produce this injury combined with information regarding the victim's seat position and direction of the impacting force should lead to a high index of clinical suspicion for diaphragmatic rupture. Chest radiography and diagnostic peritoneal lavage will establish the correct diagnosis in almost 90% of the patients with acute diaphragmatic disruption. Additional diagnostic studies are reserved for the remaining 10% of patients. Due to the pressure differential between abdomen and thorax, the natural history of these injuries is one of enlargement, and none can be expected to heal spontaneously. Once the diagnosis has been established, the treatment of every diaphragmatic disruption is surgical repair. PMID- 2589702 TI - Antibiotic therapy of life-threatening infectious diseases in the emergency department. AB - Initial therapy in acutely ill septic patients is necessarily empiric. Although a specific etiologic infectious diagnosis is rarely made in an acute situation, a treatment decision must be made and must be developed from history, physical examination, and minimal laboratory and roentgen studies. Three life-threatening syndromes are discussed: febrile-neutropenic patients with cancer, immunosuppressed patients with fever and lung infiltrates, and patients with acute community-acquired meningitis. PMID- 2589703 TI - Substance abuse education in residency training programs in emergency medicine. NIAAA Task Force of the American College of Emergency Physicians. AB - The emergency department is the focal point for many social ills, not the least of which is substance abuse. We conducted a study to determine to what degree substance abuse education is taught in emergency medicine residency training programs. A set of educational objectives was developed by a task force composed of representatives of the American College of Emergency Physicians, the Society of Teachers of Emergency Medicine, and the University Association for Emergency Medicine. A questionnaire then was sent to the directors of all emergency medicine residency programs accredited by the Accreditation Council for Graduate Medical Education to determine the degree to which those objectives are covered in residency training. A 62% response rate was achieved. The data revealed that such topics as narcotic prescription law, patterns of risk, and issues pertaining to substance abuse by physicians were covered by fewer than half of the programs responding. Respondents were generally satisfied with the adequacy of training of residents and faculty in the area of substance abuse; however, they were dissatisfied with the adequacy of available training materials. Recommendations for changes in graduate curriculum as well as avenues for further research are provided. PMID- 2589704 TI - The bone marrow as a source of laboratory studies. AB - The intraosseous route is an emergency alternative to the IV route for the administration of drugs and fluids. Another emergency function of intravascular access is obtaining blood samples for blood gases, laboratory studies, and blood cultures. One of the drawbacks to using the intraosseous route as an alternative to IV access has been the persistent need to establish IV access to obtain blood samples. We obtained bone marrow samples from ten healthy anesthetized dogs and analyzed the usefulness of the samples in providing meaningful laboratory studies when compared with simultaneous arterial and venous samples for blood electrolytes, blood chemistries, blood gases, and hemoglobin. There was no significant difference (P greater than .10) in blood electrolytes (sodium, potassium, chloride, and carbon dioxide) drawn from the intraosseous, arterial, and venous sites. The blood chemistries (blood urea nitrogen, creatinine, total protein, albumin, calcium, phosphorous, uric acid, total bilirubin, and SGOT) also were not significantly different (P greater than .10). Significant differences were obtained for glucose comparing intraosseous with arterial (P = .03), whereas intraosseous versus venous was only marginally significant (P = .06). Significant differences were also obtained for alkaline phosphatase when comparing intraosseous with arterial (P = .03), whereas comparison with venous was only marginally significant (P = .06): lactate dehydrogenase differences were marginally significant when comparing intraosseous with arterial (P = .09) and venous (P = .06) blood. Hemoglobin values were not significantly different when comparing results for the three sites (P greater than .25).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589705 TI - Traumatic central cord syndrome in a patient with Os odontoideum. AB - We report the case of a 33-year-old man who presented to the emergency department the morning after a motor vehicle accident with physical findings consistent with central cord syndrome. Radiographs of the cervical spine revealed os odontoideum. This abnormality of the odontoid process has not previously been described in association with central cord syndrome. PMID- 2589706 TI - Acute traumatic lateral patellar dislocation. AB - An unusual case of acute extra-articular patellar dislocation is described in which the patella dislocated laterally, rotated 90 degrees about its vertical axis, and wedged against the lateral femoral condyle. Closed reduction in the emergency department failed and operative intervention was required. PMID- 2589707 TI - Advance directives in emergency medicine: medical, legal, and ethical implications. AB - Emergency physicians often encounter clinical situations in which medical resuscitation may not coincide with patient expectations. These situations present complicated medical, legal, and ethical dilemmas. The history of the patient's right to refuse treatment as it applies to resuscitative medical care is reviewed. Medical recognition of patient autonomy and legal precedents affirming it are discussed, as are the various types of advance directives, including the living will and durable power of attorney and their clinical uses. PMID- 2589708 TI - More practice with pediatric patients? PMID- 2589709 TI - Care of patients attracts, retains RNs. PMID- 2589710 TI - California nurses maintain lifelines after earthquake. PMID- 2589711 TI - Councils function as catalysts for change. PMID- 2589713 TI - Research offers new knowledge for practice. PMID- 2589712 TI - AAN lays groundwork for health policy agenda. PMID- 2589714 TI - Budget reconciliation: how to do it. PMID- 2589716 TI - 1990s seen as time of transition for nursing. Interview by JoLynne Walz. PMID- 2589715 TI - Year in review 1989. ANA today. PMID- 2589717 TI - Nurses develop AIDS action agenda. PMID- 2589718 TI - Financial plan important for retirement. PMID- 2589719 TI - JCAHO plan brings change to health care. PMID- 2589720 TI - ANA plans to expand publishing effort. PMID- 2589721 TI - Nurse entrepreneurs/intrapreneurs changing health care. PMID- 2589722 TI - ANA, SNA positions call for staff nurse savvy. PMID- 2589723 TI - Bay area RNs show quick response to quake. PMID- 2589725 TI - ANA, SNAs address implications of Webster. PMID- 2589724 TI - As I see it--diversity strengthens policy directions. PMID- 2589726 TI - Nursing supply and demand. PMID- 2589727 TI - In search of a rational future for certification. PMID- 2589728 TI - Professor reveals hopes for nursing in China. Interview by Patricia McCarty. PMID- 2589729 TI - More RNs see value in collective bargaining. PMID- 2589730 TI - Debunking myths about self-quitting. Evidence from 10 prospective studies of persons who attempt to quit smoking by themselves. AB - This article examines data from 10 longterm prospective studies (N greater than 5,000) in relation to key issues about the self-quitting of smoking, especially those discussed by Schachter. When a single attempt to quit was evaluated, self quitters' success rates were no better than those reported for formal treatment programs. Light smokers (20 or less cigarettes per day) were 2.2 times more likely to quit than heavy smokers. The cyclical nature of quitting was also examined. There was a moderate rate (mdn = 2.7%) of long-term quitting initiated after the early months (expected quitting window) of these studies, but also a high rate (mdn = 24%) of relapsing for persons abstinent for six months. The number of previous unsuccessful quit attempts was unrelated to success in quitting. Finally, there were few occasional smokers (slips) among successful long-term quitters. We argue that quitting smoking is a dynamic process, not a discrete event. PMID- 2589731 TI - [Brucellosis in the Campania region]. AB - The research describes the trend of brucellosis, in the period 1984-86, in the county of the "regione Campania". This trend, in contrast with the national one, is manifested as endemic, with frequent and localised outbreaks of epidemic levels. The research also describes, through the analysis of the illness registration forms of 762 cases of brucellosis in the period 1985-86, the seasonal trend, the ages of major risk of infection and the most frequent modes of infection. The paper concludes with suggestions for the effective prevention of brucellosis. PMID- 2589732 TI - [Allergenic impurities in medicinal preparations containing aminopenicillin. I. Ampicillin sodium]. AB - High-performance liquid chromatography (HPLC) with gradient elution has been used for the determination of degradation products in pharmaceutical preparations containing sodium ampicillin. In all preparations resulting by lyophilization process, the degradation products amount, almost exclusively constituted of allergenic polymeric substances deriving from condensation reactions, is more than 10%. On the contrary, the sodium ampicillin prepared by precipitation in non aqueous solvents, only contains the 2% of polymeric impurities. PMID- 2589733 TI - [Hospital epidemic of Clostridium difficile diarrhea: demonstration of cross infection using a typing technic]. AB - Two hospital outbreaks of Clostridium difficile diarrhoea in two general surgery units of different hospitals are described. Moreover, the results of a study on the circulation of C. difficile in a neurosurgery unit following two cases of colitis are reported. C. difficile strains isolated from patients and environment have been typed using antimicrobial susceptibility testing and electrophoretic profiles of EDTA-extracted proteins. The majority of strains isolated in each hospital shared the same protein profile and the same pattern of antibiotic susceptibility. This provides strong evidence of cross-infection and hospital acquisition of C. difficile. PMID- 2589734 TI - [Control of subunit influenza vaccines]. AB - Influenza subunit vaccines contain essentially only the envelope spike proteins, haemagglutinin (HA) and neuraminidase (NA). It is important to check the purity of each monovalent batch of these vaccines, in comparison with whole virus preparation. The authors have standardized a biochemical analysis for the laboratory control of this kind of vaccines, using PAGE test. All the vaccine manufactures are required to demonstrate, by this method, that the subunit vaccine contains HA and NA, with no more than trace amounts of internal proteins. PMID- 2589735 TI - [Maintenance and care of primates in Italy]. AB - Investigation with nonhuman primates has made, and continues to make significant contribution to biomedical and behavioral research. Nowadays, laymen and scientists are becoming more concerned with the ways in which animals are maintained in captivity. In Italy, two laws (issued in 1931 and in 1941) enforce the regulations for keeping primates used for research. And more recently, the countries of the European Economic Community (EEC) have agreed on new regulations that should become law in these countries. Primates need to be in good physical and psychological health, and regulations should ensure and promote their well being. Primates' psychological well-being is characterized by: a) good physical health; b) absence of stress; c) competence in dealing with environmental and social changes; d) broad behavioral repertoire and absence of stereotyped behaviors. Enrichment procedures aimed at improving the animals' psychological well-being are discussed. PMID- 2589737 TI - Optotype distortion on the "Rosenbaum Pocket Vision Screener". PMID- 2589736 TI - [Herbicides in drinking water]. AB - Toxicological implications due to the use of herbicide-contaminated drinking water, as well as other organic chemicals, are related to their nature and levels. These implications can be defined for each substance on the basis of an adequate evaluation of epidemiological information and experimental data on animals. In this paper, World Health Organization's procedures for establishing guidelines for 11 herbicides widely used in Italy are described. Furthermore, data and information about the use of these herbicides and their levels in Italian drinking-water supplies are also reported and discussed. Finally, factors and conditions responsible for the groundwater contamination by some herbicides in determined areas are presented and discussed. PMID- 2589738 TI - Optic disc size in branch retinal vein occlusion. AB - We measured the horizontal and vertical optic disc diameters in eyes with branch retinal vein occlusion and in control eyes. No difference in the optic disc size was found between the two groups. We conclude that optic disc size is not involved in the pathogenesis of branch retinal vein occlusion. PMID- 2589739 TI - Chorioretinal anastomoses in age-related macular degeneration. AB - Both eyes (obtained at autopsy) from a 79-year-old man with a history of age related macular degeneration and glaucoma were studied. One eye was studied histologically using light microscopy and transmission electron microscopy. The other eye was prepared for scanning electron microscopy after injection of Batson's mixture into the ocular vasculature. Well-developed anastomoses between the retinal and choroidal circulation in the macular area and a pathologic tubular pattern of the choriocapillaris were found. This is an adaptation of the perifoveal circulation to changes in the fovea and a choroidal vascular response to damaged tissue. PMID- 2589740 TI - Radial keratotomy in high myopia: an evaluation of one technique. AB - Ninety-one consecutive eyes of 53 patients with refractive errors of -6.00 to 11.50 diopters (D) spherical equivalent (mean, -7.48 D) underwent radial keratotomy with redeepening and astigmatic incisions. All eyes were examined at six months, and 65.9% had one year of follow-up (mean follow-up, 11.65 months). In retrospective analysis of this group, 78% of patients had greater than or equal to 20/40 uncorrected visual acuity at six months with 76% at one year. In 59.3% of patients they were with 1.0D of emmetropia at six months with 56.7% at one year. Overcorrections (greater than +1.00D) with 11.1% at six months and 13.3% at one year. Undercorrections (greater than -1.00D) were 29.6% at six months and 30% at one year. Four patients lost two lines of Snellen visual acuity. PMID- 2589741 TI - Biomicroscopic evaluation and photography of ocular toxoplasmosis. AB - The vitreous of 39 eyes with ocular toxoplasmosis was studied and photographed using an El Bayadi-Kajiura preset lens. In active cases of toxoplasmosis, the vitreous showed inflammatory opacities and gel shrinkage. In inactive cases, the vitreous was often liquefied. Compared with 39 normal eyes of age- and sex matched controls, the prevalence of partial posterior vitreous detachment was significantly higher in toxoplasmosis (P less than .001). A higher prevalence of posterior vitreous detachment was found in eyes with the major chorioretinal lesion outside the temporal vascular arcade than in those with lesions inside the temporal vascular arcade (P less than .05). Our results indicated that various vitreous changes may cause posterior vitreous detachment and that location of the inflammatory focus may influence the vitreous condition. PMID- 2589742 TI - Factitious "calcification" in the lacrimal gland fossa. AB - Computed tomographic (CT) scans are valuable in the evaluation of lacrimal gland fossa masses. Calcification in this region is considered a sign of malignancy. Silicone implants are widely used in orbital surgery and may give the appearance of calcification on CT scan. These must be distinguished from true calcification by the proper choice of the CT scan window. PMID- 2589743 TI - Sensitivity to retinal light damage and surgical blood oxygen levels. AB - Increased oxygen levels decrease the threshold for photochemical retinal damage. We measured arterial oxygen levels in a group of ophthalmic surgical patients. As expected, levels exceeded unanesthetized measurements by one to two times. Based on experimental data, this could decrease the threshold for light-induced retinal damage during ophthalmic surgery by 40% to 50%. While the clinical implications of light-induced retinal damage in surgical eye patients are unclear, it is prudent to take steps to minimize light exposure during surgery. PMID- 2589744 TI - Methylcellulose in extracapsular surgery with intraocular lens implantation. AB - We present our experience in 28 consecutive operations using methylcellulose 2% in implantation surgery. Visual acuity of 20/40 or better was obtained in 96% of the cases. This solution is tolerated well by the human eye, protects the endothelium, maintains the depth of the anterior chamber, and facilitates the insertion of the intraocular lens. We have had no significant increases in intraocular pressure or excessive intraocular inflammation. In routine cases of implantation surgery, there is no reason to use more expensive viscoelastic substances. Because this substance is universally available, it can be prepared easily for intraocular use, and it is inexpensive making its use in developing countries strongly recommended. PMID- 2589746 TI - [Congenital perilymphatic fistula in children]. AB - We report twenty case of perilymphatic fistulae in children. A fistula was discovered in every case where the cochlear aqueduct is larger than normal on high resolution CT scan of the temporal bone. The surgical treatment of these fistulae allowed only a significant improvement of hearing in the cases were an asymmetry or a dilatation of the cochlear aqueducts and a fluctuating deafness coexisted. Unfortunately these improvements do not look permanent. PMID- 2589745 TI - Trace anesthetic gases during xenon arc photocoagulation for retinoblastoma. AB - In pediatric ocular examinations, administration of continuous-flow anesthetic gases containing nitrous oxide, halothane, and oxygen enables the physician to do safe, controlled, reproducible examinations. We did a study in which the levels of waste anesthetic gases were measured during xenon arc photocoagulation procedures used for retinoblastoma. Waste nitrous oxide and halothane gases measured during these procedures significantly exceeded the levels recommended by the National Institute of Safety and Health. These high levels are of particular importance because of the physician's proximity to the patient during the procedure. The high levels of waste gases may have immediate deleterious effects on the physician's functioning capacity and may also pose long-term health hazards for the physician and operating room personnel. PMID- 2589747 TI - [Taste disorders and associated factors in type 1 diabetes]. AB - In order to study taste in type 1 diabetes (insulin-dependent), 57 consecutive diabetic patients (mean duration of diabetes +/- SEM = 11.4 +/- 0.4 years) and 38 control subjects underwent electrogustometry and chemical gustometry. The diabetic and control group were comparable with the exception of the ponderal index which was significantly higher in diabetics (p less than 0.05). A deterioration in taste appreciation was confirmed in the diabetic group compared to the control group on electrogustometry (mean threshold: 184.3 +/- 15.8 vs 58.7 +/- 9.2 mu A; p less than 0.001) and chemical gustometry (mean score: 13.2 +/- 0.7 vs 17.1 +/- 0.8; p less than 0.001). Electrical hypogueusia was found in 73% of the diabetics compared to 16% of controls (p less than 0.001). The 4 primary tastes were involved in the deterioration. Multivariate analysis associated the taste disorder with the diabetic status of the subjects, their alcohol and tobacco consumption. In the diabetic group the deterioration in taste was associated with the complications and duration of diabetes. On multivariate analysis peripheral neuropathy had the strongest association with taste disorders. These results suggest that deterioration in taste occurs during the progression of type 1 diabetes and that the taste disorder could be a degenerative complication of the disease. A neuropathic type mechanism could be involved. PMID- 2589748 TI - [Static and dynamic posturography. Application to a population of young athletes]. AB - The authors used a vertical force platform fitted with 4 pressure gauges (Societe Toennies). The static regime provides the statokinesigram, the lateral and sagittal stabilograms and their Fourier transformations. Information is collected with the eyes open and closed, thereby allowing the Romberg quotient to be determined. In the dynamic regime, the platform unexpectedly tilts to a toes-up position (4 degrees at a rate of 50 degrees/s). The activity of the tibialis anterior and soleus muscles is recorded by integrated electromyography. The early soleal response, provoked by the myostatic reflex, is followed by later responses due to the vestibulo-spinal reflex. These various parameters were recorded in young athletes and the obtained tracings are commented on. PMID- 2589749 TI - [Benign paroxysmal positional vertigo and provocative maneuvers]. AB - Main features of the benign paroxysmal positional vertigo (B.P.P.V.) are: latency before the onset of vertigo, nystagmus of the rotatory type beating toward the lower ear, nystagmus tires out, nystagmus gets inverted when the head is brought back to orthostatism, nystagmus is reproducible as many times as the position is taken. B.P.P.V. is due to a deposit of heavy material on the cupula of the posterior semi circular canal. In this unusual condition, the cupula moves under the effect of gravity acceleration. The goal of the treatment is to free the cupula. The manoeuvre consists after determination of the position that elicits the vertigo to move the whole head and body together of the patient to a 180 degree opposite position in which the addition to the endolymph flow forces and weight forces of the material will unstick it from the cupula. The positive result of the manoeuvre is instantly proved by the arising of a rotatory nystagmus beating again toward the sick ear. In other words it is not the inversion of the primary nystagmus but a nystagmus beating the same direction. This is explained by the dynamic of the cupula: in the prime position the density modified cupula moves toward the canal. At the end of the manoeuvre when the velocity of the head is zero, the cupula has to support different forces. First the addition of the endolymph flow forces and the inertia of the heavy material makes the cupula move toward the ampulla. Secondly when the superficial tension forces are too high the heavy material unstick from the cupula and it goes back to its normal position. En this very moment the cupula moves toward the canal. The results are of more than 90% positive in one ore two sessions 4,2% of recurrence. The manoeuvre is unsuccessful in spontaneous nystagmus revealed by a position, in torsional nystagmus as in fistulas or in central position nystagmus. PMID- 2589751 TI - [Surgical importance of the nasal valve]. AB - The nasal valve is anatomically well defined, but, on a clinical point of view, it is more appropriate to talk about the nasal valve area. If the valve itself represents a three-step dynamic structure, its air-flow regulating function may be disturbed by minor adjacent structures deformations. It is of utmost importance to recognize the nasal valve dysfunction among patients with nasal obstruction complaints and to avoid any iatrogenic action at this level during rhinoplastic procedures. The various abnormalities of the nasal valve area described. Some general rules are outlined to repair this very delicate structure. In severe cases, good results are difficult to be reached. It is far better to adopt preventive rhinoplastic procedures. PMID- 2589750 TI - [Pharyngo-esophageal risk of surgery of the cervical spine using an anterior approach]. AB - The authors report six cases of pharyngo-oesophageal damage associated with fractures of the cervical spine treated by osteo-synthesis via the anterior route. These complications, not previously described, may have life threatening (especially mediastinitis) and functional consequences. They discuss the relative responsibility of: the initial trauma, which should be better defined by an initial endoscopic assessment. the surgical approach, the principles of which and its dangers and preventive aspects are discussed, early or late fixation failure justifying careful surveillance of the osteosynthesis material and in certain cases its systematic removal. PMID- 2589752 TI - [Therapeutic approach in chronic maxillary sinusitis. Apropos of 469 patients and 640 sinuses]. AB - Between 1982 and 1987 we treated 469 patients who accounted for a total of 640 involved sinuses. These patients suffered from various stages of chronic sinusitis. Endoscopy of the maxillary sinuses enabled us to collect important information regarding the state of the mucosa and secretions, to collect bacteriological samples and to inspect the ostium and take pressure measurements. There was an 80% success rate in cases of sinusitis treated by drainage. In our opinion the indication for inferior meatotomy is as an extraction procedure and is not of value for aeration drainages. Nevertheless, out of a total of 141 inferior meatotomies performed, 80% remained patent after a mean follow up period of 3 years. PMID- 2589753 TI - [Endonasal ethmoidectomy in the treatment of polyposis]. AB - The authors report their experience with 210 microsurgical ethmoidectomies carried out in 109 patients between 1980 and 1987. In 23 patients the anatomy was considerably modified due to previous surgery. Asthma was present in 56 patients and 25 patients suffered from Widal's syndrome. The complications noted included 1 case of meningitis cured by antibiotics and a case of transient diplopia. Patients were monitored for 1 to 6 years; In 69 cases no recurrence was noted (63% of cases), 31 patients (28%) only required minor local procedures for slight recurrence (28%). On the other hand, 6 patients (5.5%) required a second surgical procedure for recurrence between 3 and 6 years. PMID- 2589754 TI - [Study and surgery of diseases of the middle meatus under endoscopic control]. AB - The middle meatus is the site of abnormalities which are to a great extent responsible for naso-sinus pathology. Its exploration has benefited from improvements in optical systems (microscopes and endoscopes) and radiological investigations. We present our experience with exploration and surgery of the middle meatus under endoscopic control. The medical examination (past history, allergy, etc.) combined with radio-endoscopic findings helps to define the appropriate therapy. Functional surgery is sometimes necessary. This is performed under local anesthetic, which in our experience improves the condition for the procedure and decreases the post-operative complications. PMID- 2589755 TI - [Indications, technics and results of middle meatotomy. Apropos of 94 cases]. AB - Middle meatotomies were essentially performed during the second period of our study from 1985 to 1987. The typical indication was for closed sinusitis, in order to allow aeration and satisfactory drainage. This was performed with an optical system at 30 degrees. The technique used was an anterior approach via total unciformectomy or a posterior approach using an Ostrum forceps. Good results, i.e. meatotomies which remained patent, were obtained in 80% of cases. The mean period of follow up was 3 years (6 months to 4 years). There were few complications overall for this form of endonasal surgery, though the possibility of damage to the lacrymal duct does exist. Synechiae were the most important functional complication and need to be prevented by meticulous post-operative care. PMID- 2589756 TI - [The CO2 broncholaser in the treatment of subglottic and tracheal stenosis. Apropos of 14 cases]. AB - The authors report the results of CO2 broncholaser treatment in 14 cases of iatrogenic cricotracheal stenosis. A stable patency of the laryngotracheal airway was successfully obtained in 43% of stenoses treated with the broncholaser alone. In another 43% of patients improvement was obtained. Failure occurred in 14% of cases. Heat disruption of the cartilagenous support was the most frequent cause of failure and recurrence. The development of rigid bronchoscopes which can be coupled to CO2 laser would appear to us to be a real technical advance. The apparatus is easy to handle and is increasingly being used as first intention. It has several advantages compared to endoscopic materials used with the YAG laser. The effect of CO2 on the tissues would seem to be better adapted than the YAG for iatrogenic stenoses. PMID- 2589757 TI - [Endoscopy and cophosurgery]. AB - Certain fixed adherent retraction pockets especially in the posterior aspect of the tympanic cavity and certain cholesteatomas are difficult to treat even after a posterior tympanotomy has been performed. Using 70 degrees and especially 30 degrees optical systems can be of great value as the lesions can be perfectly visualised and endoscopic copho-surgery itself can even be carried out. Study of 27 cases of fixed retraction pockets and 14 cholesteatomas which underwent microscopic surgery but with optical verification of the operative cavity demonstrated the value of this technique. The safety of the method even allows the exclusive use of the endaural route in cases which have up to now required a posterior approach and posterior tympanotomy. PMID- 2589758 TI - Applications of the voice prosthesis during laryngectomy. AB - With the recent introduction of the voice prosthesis for alaryngeal speech rehabilitation, its application in the early postlaryngectomy period is gaining acceptance. One hundred twenty-eight patients received a tracheoesophageal puncture and adjunctive pharyngeal constrictor relaxation during laryngectomy. The voice prosthesis was applied as early as 10 days after surgery, and the results of a 9-year experience are presented. Eighty percent of the population achieved a durable voice, and the complications were infrequent. The results support the primary use of tracheoesophageal phonation as a relatively safe and reliable alternative to total laryngectomy alone. PMID- 2589759 TI - Sliding flap tracheoplasty. AB - The optimal method for surgical management of subglottic stenosis is based upon careful assessment of the location, caliber, length, and maturity of the stenotic segment, as well as associated conditions. For patients with a mature stenosis of short length, excision of the anterior arch of the cricoid and first ring and immediate reconstruction by means of a sliding flap of the next two to three rings of trachea offer a one-stage definitive treatment without the need for grafting. We report four cases of subglottic stenosis and one case of cricoid chondroblastoma in which reconstruction of the airway was successful and prompt. For carefully selected cases, sliding flap tracheoplasty may be a useful alternative to procedures in which the airway is expanded by means of grafting. PMID- 2589760 TI - Carbon dioxide laser posterior cordectomy for treatment of bilateral vocal cord paralysis. AB - Upper airway obstruction due to bilateral vocal cord paralysis was successfully relieved by carbon dioxide laser posterior cordectomy. All patients achieved satisfactory airway and decannulation. Flow-volume loop spirograms obtained preoperatively and postoperatively documented improved flow rates on inspiration and expiration. Final voice quality was subjectively good in all patients. Follow up has ranged from 1 year 10 months to 5 years 8 months, and initial improvement has been sustained in all cases. Carbon dioxide laser posterior partial cordectomy is an alternative management option for relief of upper airway obstruction due to bilateral vocal cord paralysis. The procedure can be performed without prophylactic tracheotomy. Subjectively good voice quality is preserved. PMID- 2589761 TI - Prospective studies evaluating the standard endotracheal tube and a prototype endotracheal tube. AB - Two prospective studies were designed to evaluate laryngeal injury sustained with the standard endotracheal tube (ETT) and the relative safety of a new prototype ETT. The first study followed patients after prolonged intubation with the standard ETT. Potential patient host factors were recorded and correlated with subjective complaints and objective findings on fiberoptic laryngoscopy. Nearly all patients sustained laryngeal injury after prolonged intubation, although over two thirds experienced resolution. Nasogastric feeding tubes and larger-diameter ETTs were associated with true vocal cord (TVC) granuloma formation. Duration of intubation was associated with delayed TVC immobility. The mechanisms of TVC granulomas and immobility are probably different, as suggested by the different host factor associations and onset times. The second study compared the standard ETT with the prototype ETT in short-term intubations. The prototype ETT was associated with no complications in this setting and is considered relatively safe for further testing in the patient with prolonged intubation. PMID- 2589762 TI - Auditory brain stem responses to bone-conducted tones in infants. AB - The auditory brain stem responses (ABRs) to 500- and 2,000-Hz bone-conducted (BC) tones were recorded from 48 infants with ears exhibiting various external and middle ear states (normal, otitis media, auditory meatal atresia). Amplitudes were greater, wave V latencies longer, and detectability better for responses to 500-Hz BC tones compared to 2,000-Hz BC tones. Overall, most (94% to 100%) infants with normal cochlear sensitivity demonstrate ABRs to 20-dB normal hearing level (nHL) 500-Hz BC tones and 30-dB nHL 2,000-Hz BC tones. In cases in which masking is difficult (eg, bilateral atresia), infant ipsilateral/contralateral ABR asymmetries may help determine from which cochlea a response to the BC tones originates. In conclusion, two-channel ABR recordings to BC tones appear to be feasible for demonstrating normal cochlear sensitivity in infants. PMID- 2589763 TI - Audiologic threshold monitoring of patients receiving ototoxic drugs. Preliminary report. AB - An effort was made to determine the efficacy of auditory threshold monitoring of patients receiving ototoxic drugs. Forty-four patients treated with either tobramycin or vancomycin for osteomyelitis were tested at the beginning of treatment, following treatment, and twice weekly during treatment when possible. All patients had renal function carefully monitored. Peak and trough drug levels were kept out of the toxic range throughout the study. In no patient did indisputable ototoxicity occur, and therefore, no conclusion about the most efficacious schedule for auditory monitoring of patients receiving ototoxic drugs was made, and what constitutes a significant intratherapeutic threshold shift is still in question. Until further data are collected, monitoring of renal function and peak and trough drug levels, as well as patient counseling, is recommended. Pretherapy and posttherapy auditory monitoring and intratherapeutic monitoring of high-risk patients and those who develop aural symptoms may prove beneficial. PMID- 2589764 TI - Sternomastoid tumor of infancy. AB - Sternomastoid tumor of infancy (SMTI) is the most common cause of neck mass in the perinatal period. We present seven children with this disorder, six studied prospectively. Ages at presentation ranged from 1 week to 4 weeks. Five had a history of birth trauma. Torticollis with facial asymmetry was seen in two. In six the diagnosis of SMTI was made clinically, and these patients were managed conservatively with massage and controlled stretching of the neck. Resolution of the neck mass, the torticollis, and the facial asymmetry occurred in all patients. Pathologic and radiographic findings are presented. We conclude that careful clinical assessment precludes the necessity of biopsy and emphasize the importance of conservative management of this transient problem. PMID- 2589765 TI - Duration and frequency characteristics of tracheoesophageal speech. AB - Selected characteristics were compared in the speech of five tracheoesophageal, five esophageal, and 15 normal laryngeal adult speakers. Tape-recorded speech samples were measured for durational features with a stopwatch. Frequency features were analyzed with a Visi-Pitch/Apple IIE computer interface with statistical subroutines. Tracheoesophageal speech proved comparable to normal speech in maximum phonation time, speech rate, pitch pertubation (jitter), average fundamental frequency, and fundamental frequency range, but less efficient than normal speech in phrase grouping. Tracheoesophageal speech was superior to esophageal speech in maximum phonation time, speech rate, and phrase grouping, but not significantly different in pitch perturbation, average fundamental frequency, and fundamental frequency range. Explanations and clinical implications of these findings are discussed. PMID- 2589766 TI - Surgical implantation and biocompatibility of central nervous system auditory prostheses. AB - As part of a program to determine the feasibility of a CNS auditory prosthesis, the tissue reaction to electrodes chronically implanted in the cochlear nucleus (CN) of the guinea pig was examined. Varied open operative approaches and microelectrode designs were utilized. Silicon substrate thin film and platinum iridium wire electrodes, tethered and untethered, were placed successfully in different divisions of the CN. Implantation through a posterior suboccipital approach was most successful. Histologic examinations demonstrated a glial cell proliferation confined to the area of the electrode track that never exceeded 15 microns in width. No neuronal loss or significant effect on cell morphology was seen, and reactive cells were absent. Electrode migration was apparent in a minority of animal preparations. Although potential problems were identified, our findings lend support to the feasibility of implanting a neuroprosthesis in the CN and have helped to establish methods for future studies of chronic intranuclear stimulation. PMID- 2589767 TI - Osteosarcoma of the larynx. AB - A case of laryngeal osteosarcoma in a 75-year-old man is described. The osteosarcoma probably arose by dedifferentiation of a chondrosarcoma of the cricoid cartilage. Laryngeal osteosarcoma is rare: the literature is reviewed and management discussed. PMID- 2589768 TI - Immune response of the endolymphatic sac to horseradish peroxidase: immunologic route from the middle ear to the inner ear. AB - Twenty guinea pigs were immunized with horseradish peroxidase (HRP) intradermally and challenged with 5 mg of the same antigen in the tympanic bulla. The appearance of immunoglobulin-producing cells (plasma cells) in the inner ear structure was examined immunohistochemically in frozen sections. Four to 10 days following antigen challenge, 5 of the 20 animals showed significantly increased plasma cells in the subepithelial connective tissue of the endolymphatic sac (ES). Those cells showed positive reactions, mainly with IgG followed by IgM. The cells that reacted positively with IgA were few. Some of these plasma cells were considered to contain the specific antibody against HRP. The results indicate the role of the ES as a local immune response region for the inner ear complex, as well as the existence of an immunologic route from the middle ear cavity to the inner ear, particularly to the ES. PMID- 2589769 TI - Round window membrane and perilymph in experimental otitis media with effusion. AB - To investigate the influence of middle ear effusion (MEE) on perilymph (PL), an experimental otitis media with effusion (OME) was manufactured in chinchillas by injecting the tympanic cavity with immune complexes. The presence of MEE lasted for up to 9 days after the injection of immune complexes. Perilymph was aspirated on the fourth, tenth, and 21st days after the inoculation. The mean concentrations of albumin, immunoglobulin G, histamine, and prostaglandin E2 (PGE2) were significantly greater in PL from ears with induced OME than in that from normal control ears. The 3H-PGE2 placed on the round window membrane of pathologically affected ears passed into PL in significantly greater amounts than in normal control ears. The findings indicate that the immune complexes placed in the middle ear cavity affect the biochemical milieu of PL, and that MEE is a result of immune complexes. PMID- 2589770 TI - Maxillary sinus neoplasm. PMID- 2589771 TI - [Treatment of pneumococcal infections in children]. PMID- 2589772 TI - [Acute viral hepatitis in children: management]. PMID- 2589773 TI - [Lyme disease in children]. PMID- 2589774 TI - [The management of infants born to HIV-positive mothers]. PMID- 2589775 TI - [Should we abandon the diagnosis of asthmatic bronchitis?]. PMID- 2589776 TI - [The role of medium chain triglycerides in pediatric nutrition]. PMID- 2589777 TI - [The management of familial hyperlipidemia diagnosed in childhood]. PMID- 2589778 TI - [The evaluation of nutritional status in pediatric practice]. PMID- 2589779 TI - [New household hazards for children]. PMID- 2589780 TI - [Evaluation of more than 1,000 surgical procedures under general anesthesia, performed in children less than 15 years of age at a day hospital]. PMID- 2589781 TI - [Fetal surgery: future perspectives]. PMID- 2589782 TI - Skin malignancy and the reconstructive plastic surgeon. AB - Skin malignancy represents at least 25% of the plastic surgeon's workload. The commonest tumour, the basal cell carcinoma, usually arises in the skin of elderly patients who are frequently managed by surgery under local anaesthetic, often as outpatients. The recurrent basal cell carcinoma poses a difficult problem regardless of the primary therapy. Skin repair with direct closure or skin grafts is usually simple, but skin flaps will be needed when bone, cartilage or major neurovascular structures are exposed, or where tissue vascularity has been reduced by irradiation fibrosis. Squamous cell carcinomas of lip, ear and hand may recur as lymph node metastases despite clinical and histological clearance. Malignant melanoma continues to present as advanced disease (thick tumours) in this country, and this largely dictates prognosis, since tumour thickness is recognised as the single most important dominant prognostic variable. Incisional biopsy compromises histological microstaging and should be avoided. Indirect evidence from narrow margin excision of invasive head and neck cutaneous melanomas suggests no detriment, and narrow margin excision of melanomas is increasingly being practised. PMID- 2589783 TI - Free flaps in reconstructive surgery. AB - Advances in technique, training and instrumentation have improved the patency rates for small vessel anastomosis. This, together with the introduction of more reliable donor sites for free tissue transfer, have resulted in success rates in excess of 90%. The technique is not associated with an increase in mortality or morbidity; on the contrary there is the advantage of primary reconstruction with a wide choice of donor sites offering the correct amount and type of tissue required. Single-stage, effective reconstruction, aimed at primary wound healing remains the aim of the reconstructive surgeon and free tissue transfer offers the most versatile and reliable method currently available. PMID- 2589784 TI - Tissue expansion in perspective. AB - Tissue expansion is a recent advance in skin cover technique. Its empirical use has enabled many previously difficult reconstructions to be completed without recourse to distant flaps. Its high complication rate and lack of basic scientific understanding at present restrict its use to selected cases, but the quality of repairs possible by this method encourage further serious scientific study. PMID- 2589785 TI - Cranio-orbital trauma: a team approach to management. AB - We present 48 patients having multidisciplinary management following severe trauma to the fronto-orbito-nasal area. Surgical methods, including a preliminary debridement and later comprehensive repair are described in detail and results and problems are discussed. We wish to emphasise the better functional and cosmetic results that are gained by undertaking a comprehensive repair in the early post-injury phase, avoiding late intracranial infection, secondary surgery and prolonged hospitalisation. The techniques require cooperation between a reconstructive surgeon and a neurosurgeon. PMID- 2589786 TI - Cosmetic surgery. AB - The psychotherapeutic nature of cosmetic surgery is emphasised by outlining the range of symptoms from which patients suffer and by explaining the sequence of psychological reactions which cause them. The principles which govern the selection of patients are defined. A brief account of each of the main cosmetic operations is given together with notes on their limitations and risks. PMID- 2589787 TI - Lower limb trauma: primary treatment and reconstruction. AB - The requirements of lower limb trauma reconstruction are discussed with comment on the availability of plastic surgery services. The significance of early efficient soft tissue management is stressed and a plea is made for better cooperation between plastic and orthopaedic surgery in both training and practice. PMID- 2589788 TI - An evaluation of expanded polytetrafluoroethylene (PTFE) loop grafts in the thigh as vascular access for haemodialysis in patients with access problems. PMID- 2589789 TI - Early postoperative endoscopic sphincterotomy for retained biliary stones. PMID- 2589790 TI - The practical management of Fournier's gangrene. PMID- 2589791 TI - The surgical correction of mandibular prognathism using rigid internal fixation- a report of a new technique together with long-term stability. PMID- 2589792 TI - [Atypical heart transplantation. Technical considerations. Apropos of a case]. AB - A heterotopic heart transplantation was performed on a patient placed on circulatory assistance with a Biomedicus pump for ten days using a heart taken from a donor with situs inversus. In relation to this case, the authors describe the technical procedures allowing transplantation of a heart obtained from a donor with situs inversus into a heterotopic position and an orthotopic position or a normal heart in a recipient with situs inversus. Lastly, in the case of complex cardiac malformations with preservation of the lungs, they present the procedures allowing heart transplantation in cases of situs incertus, anomalies of venous return and transposition of the great vessels. PMID- 2589793 TI - [Double lung transplantation. Report of the 1st French case and comments on the 5 subsequent cases]. AB - Using a modified version of the technique described by the Toronto group, the Marseille group has performed 6 double lung transplantation procedures. In 6 cases the underlying disease was cystic fibrosis. Four patients are currently alive. The technique was modified in two ways. First anastomosis was made on the two main stem bronchi in order to rule out the risk of ischemic complications. Second a special postoperative care technique in which the patient is regularly turned from one side to the other was applied to avoid lymph stasis during the first postoperative weeks. PMID- 2589794 TI - [Lung and heart-lung transplantation in respiratory tract diseases. Evaluation and development of the indications based on our first 15 cases]. AB - Since January 1988, the Bordeaux group has performed 15 transplantations for lung disease: 9 heart-lung transplants, 1 heart + left lung, 1 double lung, 2 right lungs and 2 left lungs. The transplantations were performed for pulmonary emphysema (10 cases), pulmonary artery hypertension (2 cases), cystic fibrosis (1 case), pulmonary fibrosis (2 cases). Cardiopulmonary transplantation was not always performed because of associated heart failure but sometimes because of large intrahilar adenopathy or intractable bronchial infection. Pulmonary transplantation is recommended on the right side in cases of pulmonary fibrosis. One patient died postoperatively (ischaemia of the transplant). Four others died during the 2nd and 3rd months from poorly defined but probably infectious pulmonary syndromes. The tracheobronchial patency of the 10 survivors was 80% or 100% of the predicted value. The respiratory functional result was excellent in the short and intermediate term. Specific difficulties essentially consisted of pleural symphyses, hilar adenopathy, bronchial infection, steroid dependence of certain subjects, the difficulty of identifying the cause and treating lung opacities during the 2nd and 3rd months. PMID- 2589795 TI - [Long-term results of isolated aortic valve replacement using a Bjork-Shiley prosthesis. A clinical study of a series of 365 patients with a postoperative follow-up of 8 to 16 years]. AB - 365 patients (mean age: 59 years) surviving isolated aortic valve replacement performed between 1971 and 1978 by means of a standard flat disk Bjork-Shiley prosthesis, underwent regular and complete follow-up (100% survival rate) representing 3,248 patient-years with a maximum follow-up of 15.4 years (mean: 8.9 years). All of these patients received anticoagulant treatment, which was considered to be well-controlled in 90.5% of cases. 121 secondary deaths (33.1%) were observed. Cardiac causes were the most frequent (35/121, i.e., 28.9%). Four deaths were directly related to the prosthesis (2 infections, 1 thrombosis, 1 dysfunction). Twenty deaths (16.5%) were related to cerebral vascular accidents and 2 (1.6%) to haemorrhagic complications. In 24 cases, the cause of death could not be determined (19.8%). Overall, 1 out of 5 deaths (21.4%) was directly or indirectly related to the prosthesis. The actuarial survival rate was 85.5% at 5 years and 67.9% at 10 years. Seventeen thromboembolic complications (7 lethal, 10 non-lethal) were observed and represented a linear incidence of 0.5% per patient year. Fourty-one haemorrhagic complications were observed in 28 patients, i.e. a linear incidence of 1.26% per patient-year. Nine reoperations were necessary, responsible for 3 deaths. No cases of mechanical failure of the prosthesis were observed. All of the lethal and non lethal complications related to the prosthesis represented a linear incidence of 2.6% per patient-year. AT 5 and 10 years after the operation, 89.2% and 79.6% of the patients were free of any valve related complications. The functional results was considered to be good or excellent in the very great majority of surviving patients (97.8%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589796 TI - [Durability of the Carpentier-Edwards porcine bioprosthesis in aortic or mitral positions. 10 years' results on 458 surgically treated cases]. AB - 458 patients with a Carpentier-Edwards porcine bioprosthesis (aortic (Ao): 169, mitral (Mi): 289) operated between January 1975 and December 1981, were studied during the first trimester of 1987. Forty seven patients underwent an associated operation. The total follow-up was 3,001 patient-years with a maximum follow-up of 11.4 years and a mean follow-up of 6.5 years. Only 5.6% of patients were lost to follow-up. The patients were aged between 20 and 80 years. The actuarial 9 year survival rate was 69.2 +/- 6.3% for aortic prostheses and 79.6 +/- 3.9% for mitral prostheses. The principal cause of valve failure, appearing with a considerable frequency after 5 years, was primary tissue degeneration which alone represented 67.8% of the causes of valve failure. The rate of absence of valve failure, for all causes combined, was 77.8 +/- 5.9% for the aortic position and 74.9 +/- 4.9% for the mitral position. The actuarial rate of absence of primary tissue degeneration at 9 years was 79.7 +/- 4.1% for aortic prostheses and 75.2 +/- 4.4% for mitral prostheses. The frequency of tissue degeneration decreased with increasing age, representing 2.9%, 1.9% and 1.5% patient-years respectively for the age-groups: 20 to 39 years, 40 to 59 years and 60 to 80 years. However, this difference was not statistically significant. Tissue degeneration was the principal cause for reoperation (n = 59) with an operative mortality of 7.8%. PMID- 2589797 TI - [Late results of myocardial revascularization surgery in patients with severe impairment of left ventricle dynamics. Apropos of 80 cases surgically treated from 1970 to 1979]. AB - Coronary bypass surgery was performed on forty-eight patients with LVD from 1970 to 1979. Mean age was 53 +/- 9 years. All patients had abnormal motion of all walls on cineangiography and three vessel disease. Mean LVEF was 27.7%. Mean of distal anastomoses was 1.6 per patient with internal mammary artery graft to LAD. Six patients died early postoperatively (7.5%) and there were 31 late deaths. Actuarial survival including early deaths is 71.5 (+/- 6)% 5 years and 49% 10 years postoperatively. LVEF has a significant influence upon late survival (p 0.01). Because of incomplete revascularization, 55% of the 40 surviving patients, have recurrence of angina with a mean follow-up of 103 months. We have subsequently increased the mean number of bypass grafts in these patients. PMID- 2589798 TI - [Ultrastructural changes in the saphenous vein removed during aorto-coronary bypass]. AB - In order to observe ultrastructural changes of the saphenous vein before implantation during coronary artery by-pass surgery, 58 fragments from a series of 29 consecutive patients, were studied by means of scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Two fragments were taken: the first just before the distal anastomosis; the second just before the last anastomosis on the aorta. The vein graft was kept in a finger solution of 10% nitroglycerin. Forced dilatation was avoided. The EM showed areas of early loss of the endothelial layer, not time-related, deposits of fibrin and blood corpuscular elements with muscular contraction in 75% of the examined grafts. From our experience and according to the literature, loss of the endothelial layer, spasm and early platelet and fibrin aggregation, are constant features of the explanted saphenous vein. In clinical practice, we emphasize, in addition to the "no touch technique", the early use of antiplatelet drugs during coronary artery by-pass coronary surgery. PMID- 2589799 TI - [Clinical and metabolic evaluation of myocardial protection by oxygenated cardioplegia (Hamburg solution) in multiple coronary bypass surgery or polyvalvular replacement]. AB - Myocardial protection by the Hamburg oxygenated crystalloid cardioplegic solution was evaluated. A prospective metabolic study was conducted by measuring the myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) contents by enzymatic techniques in 30 coronary bypass patients with a mean of 3.5 (+/- 0.9) aorto-coronary bypass grafts. Mean aortic cross clamp time was 48.4 (+/- 9.8) min. Myocardial samples were obtained from the left anterolateral ventricular wall: 1 = before CPB, 2 = before aortic cross clamp removal, 3 = 10 min following reperfusion. During ischemia, there was no statistically significant decrease in myocardial ATP contents [3.26 (+/- 0.82) vs 3.01 (+/- 0.92) mumol/g of frozen weight]; in contrast myocardial CP contents decreased significantly [2.71 (+/- 1.44) vs 1.87 (+/- 1.19) mumol/g; p = 0.01]. Following 10 min of reperfusion, the mean ATP level [2.96 (+/- 0.84) mumol/g] was 90% of the preischemic value, and myocardial CP levels (2.32 (+/- 0.92) mumol/g] increased to 85% of preischemic levels. Spontaneous myocardial defibrillation was observed in 93.3% of cases. Early postischemic myocardial function was studied in 228 cardiac operations using the same myocardial protection. 48 patients underwent multiple valve replacement (MUVR), and 180 patients had 4 or more aorto-coronary bypass grafts (CABG). Spontaneous myocardial defibrillation was observed in 90.3% of all; cases; mean CPB time after aortic cross clamp removal was 10.3 (+/- 8) min. Cardiac index by Swan-Ganz thermodilution catheter were measured just before cardiopulmonary bypass and one and twelve hours later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589801 TI - [Lung cancer with mediastinal lymph node involvement. Results of the combination of surgery and radiotherapy]. AB - From July 1979 to July 1986, 215 patients with non-oat cell carcinoma of the lung were treated by surgery at our institution. Of these, 169 had complete, potentially curative resection of their primary tumor and all accessible mediastinal lymph nodes. The extent of pulmonary resection consisted of pneumonectomy in 70 patients, lobectomy in 78 patients, bilobectomy in 18 patients and wedge resection in 3 patients. All were staged according to the AJG staging system. There were 88 patients without lymph node metastases (N0), 10 patients with peribronchial lymph node metastases (N1) and 60 patients with regional lymph node metastases (N2). All patients with N2 disease received radiation therapy to the mediastinum after surgery. The overall survival rate was 62% at 1 year, 36% at 3 years and 27% at 5 years. Survival in patients with N2 disease was 56% at 1 year, 23% at 3 years and 12.4% at 5 years. We conclude that patients with mediastinal lymph node metastases can be effectively treated by combined resection and radiation therapy, with prolonged survival. PMID- 2589800 TI - [Multiple primary lung cancers. The importance of early diagnosis and survival after a new surgical excision]. AB - In a series of 1.025 consecutive resections for bronchogenic carcinoma, 68 patients developed a second primary lung cancer identified as the first site of recurrence (median interval of 38 months). Thirty-nine patients (57%) were asymptomatic (detection by chest-X-Ray (N: 28] or sputum cytology (N: 11) and 22 had one or more symptoms. A reoperation was possible in 50% (N: 34) of all patients with an operative (30 day) mortality of 14.7% (5/34) as compared to 3.5% (26/1.025) for the first procedure. Cumulative survival following the second resection was 33% at 5 years while no inoperable patient survived longer than three years. Clinical presentation of the second carcinoma is a significant prognostic variable since no symptomatic patient survived more than two years while 30% of the asymptomatic group survived 5 years (p less than 0.021). PMID- 2589802 TI - [Value of hemodynamics in the surgical indications of emphysema]. AB - The authors present the results of a preliminary study designed to define the surgical indications in diffuse pulmonary emphysema based on the data of haemodynamic investigations. This series consists of 10 patients identified for disabling dyspnoea, diffuse emphysema and dynamic expiratory compression documented by the data of right micro-catheterisation by a DEP/DIP ratio greater than 2. The surgical operation consisted of reduction in the lung volume, the results of which were defined by pre- and postoperative examinations. In this way, it is possible to distinguish 3 groups of patients: one group was markedly improved, another was moderately improved and the third group continued to deteriorate analysis of the results suggests the determinant role of dynamic factors, in particular haemodynamic factors. The role of the diaphragm is demonstrated by modifications in its radius or curvature. PMID- 2589803 TI - [Resection and reconstruction of the carina with separate two-lung high-frequency jet ventilation]. AB - Carinal resection and reconstruction via a right transpleural approach in an hypoxemic patient provides difficult maintenance of satisfactory gas exchange when one lung ventilation is inadequate. The present case report concerns a 62 year-old patient with chronic obstructive airways disease and a carinal squamous cell carcinoma. He underwent tracheobronchial reconstruction surgery by Barclay's procedure through a right postero-lateral thoracotomy. During resection and reconstruction phases, the gas exchange was maintained by a new technic: high frequency-jet-ventilation (HFJV) with two small-bore catheters through the endotracheal tube and JVHF ventilators adjusted to the compliance of each lung (high for the right lung, low for the left one). No circulatory changes were observed during the sutures lines phase (90'). The oximeter and the arterial blood gas values show an adequate procedure. The immediate post operative period was unremarkable and uncomplicated. The histological diagnosis was squamous cell carcinoma involving the carina with one metastatic pretracheal lymph node and microscopic infiltration of the left main bronchus resection margin. Sixteen grays postoperative radiotherapy was required. Ten months after the patient is alive, without tumor recurrence. HFJV greatly facilitates surgery by avoiding endobronchial intubation with large cuffed tubes into the surgical field. In patients with low pulmonary reserve, bilateral lung HFJV is required: two JVHF ventilators with different ranges delivering separate ventilation to the right and left lungs avoid left hypoventilation and right surgical emphysema and insure good surgical conditions. PMID- 2589804 TI - [Apropos of 6 para-esophageal cysts. A discussion about their origins]. AB - Para-oesophageal cyst is a rare lesion which can be classified, by its origin, as a gastrointestinal duplication. It is mostly encountered in children. Since 1977, we have observed 6 cases in adults, and 5 out of 6 presented as postero-inferior mediastinal tumors. Pre-operative diagnosis is difficult: when the lesion is intramural, the only other diagnosis is leiomyoma; in other cases, a bronchogenic cyst or a posterior mediastinal enteric formation can be discussed. Surgical findings and histological criteria allow a precise definition of these cysts, which lie at least partially in the wall of the oesophagus. They are a histological association of respiratory mucosa and muscular, either of type or associated with cartilaginous islets. The definition of the clinical classification is easier with a good knowledge of the histogenesis. PMID- 2589805 TI - [Is home thrombolysis of myocardial infarct realistic?]. AB - Based on a 19-month experience of intravenous thrombolysis performed at home during the acute phase of myocardial infarction, we feel it is a realistic procedure, since it did not result in too many unnecessary calls: in 648 calls which seemed attributable to a coronary emergency by the Emergency Medical Services, this diagnosis was ruled out in 119 instances (18.4%) and confirmed in 529 instances (81.6%); diagnostic errors were not too frequent: 3.8 p. cent of false positive and 5.8 p. cent of false negative; it was not very hazardous: one death only from cardiogenic shock; it permitted to save time by decreasing by 30 minutes the start of the treatment; it avoided excessive costs by using already established structures. PMID- 2589806 TI - [Improvement of left ventricular function after fibrinolysis using intravenous streptokinase]. AB - Over a period of 13 months, 33 male patients, under the age of 72 years, admitted in the cardiology department following a myocardial infarction within 5 hours after painful onset, and treated with intravenous fibrinolytic agents, were included in this study. A coronary angiography with right anterior oblique ventriculography at 30 degrees was performed. Within the first 72 hours. The informations provided by this examination resulted in a coronary angioplasty performed in patients, a by-pass in 4 patients and medical treatment in 13 patients. After a mean delay of 8 months, a new control was performed using iodine ventriculography study of radial and segmental shortening fractions, Leighton's rotation). The results expressed, concern the sub-group of non surgical patients: regardless of the site of the infarction, the percentage of akinesis (% AK) goes from 15.0 +/- 12.0 p. cent to 8.3 +/- 10.3 p. cent (p less than 0.01). The stroke volume (SV) is not significantly improved. In the group of inferior necroses, the global SV goes from 58.4 +/- 10.1 p. cent to 62.9 +/- 10.8 p. cent; p less than 0.05 and the % AK goes from 13.9 +/- 11.5 p. cent to 5.0 +/- 5.6 p. cent; p less than 0.001). Segmental kinetics in the inferior and infero basal territories is significantly improved at eight months. In the anterior necrosis group, the study of the same parameters does not demonstrate any significant difference (too limited population). The imputability of the improvement of the parameters of the left ventricular function by arterial revascularization is clearly suggested by these results. PMID- 2589807 TI - [Fulguration of the bundle of His. An explanation based on 128 consecutive personal cases]. AB - Fulguration of the bundle of His consists is interrupting or markedly slow-down the atrio-ventricular conduction, in order to suppress or markedly decrease the symptoms related to refractory atrial arrhythmias. With a consecutive series of 128 cases, it is possible to specify the main indications and present a simplified technique, using Josephson's catheter. At 3 months, the results are as follows: 3rd degree atrio-ventricular block in 80 p. cent of the cases, 1st degree atrio-ventricular block in 10 p. cent, with failure in 10 p. cent of the cases. The immediate complications are rare and benign. Late complications are essentially related to the type of cardiac stimulation offered to the patient. The ventricular stimulation with dependent frequency (particularly on ventilation), enables most patients to return to a normal activity. PMID- 2589808 TI - [Fulguration and pre-excitation syndrome. Results in 121 patients]. AB - Ablation of accessory pathway (AP) of any location was performed either with a right or a left approach (patent foramen ovale, transpeptal or a retrograde transvalvular aortic catheterism in 121 patients. The best ablation site was localized: 1) by the recording of a potential likely with the Kent bundle activation; 2) the earliest site of retrograde atrial activation during orthodromic reciprocating tachycardia (80 +/- 35 ms); 3) first ventricular potentials recorded ahead or synchronous with the delta wave in standard leads; 4) disappearance of preexcitation due to the pressure of the catheter on the AP (8 patients); 5) good degree of pace-map concordance with the major preexcitation. Two 160 joules cathodic shocks in close succession induced the disappearance of preexcitation in 113 patients. No recurrence of arrhythmia occurred in 118 patients without any preventive treatment with a follow-up ranging from 2 to 49 months (10 +/- 8). No serious side effect were observed except three permanent complete AV block. However one of them occurred after an unsuccessful surgical attempt which obviously had damaged the AV junction. Fulguration is efficient in any location of AP and can be the first line treatment in patients at risk with the WPW either symptomatic or not. These results indicate that appropriate treatment of patient the Wolff-Parkinson-White syndrome could be reassessed. PMID- 2589809 TI - [Treatment of ventricular tachycardia using endocavitary fulguration. 5 years' experience with 53 cases]. AB - 53 patients, between the ages of 14 and 76 years, presented a ventricular tachycardia which was treated by the fulguration method. 19 resulted from a complication of an old myocardial infarction, 15 from a right arrhythmogenic ventricular dysplasia, 8 from a dilated myocardiopathy. 10 patients presented idiopathic tachycardias: 3 originated in the infundibulum of the right ventricule and 7 from the left ventricle. One case originated from a surgical scar of the infundibulum. These tachycardias were continuous or occurred daily in half of the cases, or presented monthly recurrences. 1 to 17 shocks were delivered at each session, 143 on the right, 112 on the left and 2 transseptal. Four patients died from haemodynamic deterioration prior to the shock. The other 49 patients are considered as clinical successes. Three died within the first three months of low cardiac output without any recurrence of the tachycardia. 26 did not longer present any recurrent tachycardia and were not given any preventive anti arrhythmic treatment. 19 developed recurrence or could be triggered off again, but the anti-arrhythmic medications which were ineffective, become effective. One female patient again developed slavos of ventricular tachycardia after a few months. Seven patients died 4 to 18 months after fulguration, and three presented a sudden death. They belong to the group with medically treated recurrences. This technique is a major factor in the therapeutic strategy of ventricular tachycardias, either used alone or associated with a pharmacological treatment. PMID- 2589810 TI - [Evaluation of the readaptation of patients with triple coronary vessel disease unfit for by-pass surgery]. AB - The objective of this study is to evaluate the effects of rehabilitation in 46 consecutive patients with triple vessel coronary disease, and unfit for by-pass surgery: there were 45 men and 1 woman (mean age = 58 years), admitted during the 3rd week of a myocardial infarction (N = 31) or following unstable angina (N = 15). The stroke volume (SV) is normal in 50 p. cent of the patients, but 15 p. cent presented as SV less than 0.30. 3 patients were unable to start their rehabilitation because of unstable angina (N = 2), or severe pulmonary edema (N = 1). Following 4 weeks of rehabilitation, comparison of the stress tests pre- and post-rehabilitation, reveals improved functional capacities (maximum level reached 103.6 +/- 27 vs 126.4 +/- 31; p less than 0.001, and an improvement of the ischemic threshold (82 +/- 32 vs 92 +/- 31; p less than 0.05). During the long-term follow-up (32.5 months), 4 patients died from cardiac complications (8.7%) and one from extra-cardiac reasons. Among the 41 alive patients, 58.6 p. cent were asymptomatic, 39 p. cent presented cardiac complications, one had a GI malignancy. The rate of return to work among the active population is 68.5 p. cent within a mean time of 1.7 months after rehabilitation. Overall, this study demonstrates the possibility of cardiac rehabilitation under medical supervision in patients with severe triple vessel coronary disease. The improvement of the functional abilities under stress conditions is obvious, enabling the patient to regain confidence in him/herself and improve his/her comfort. PMID- 2589811 TI - [Transesophageal, anatomic and Doppler echocardiography. Technic, indications, interpretation]. AB - Cardiac ultrasonography completed by the Doppler technique has demonstrated his ability to visualize almost all of the anatomical pathology including description and semi-quantification of pathological blood flows within the heart. However, the physical properties of the ultrasound beam frequently limit the imaging process and Doppler flow studies. Absorption of ultrasound by the chest wall is a major determinant of quality and hence interpretation, together with the depth of the examined zone of interest. It's a common finding that echo-Doppler images are better in children than in obese adults. Moreover, strong echo-reflectors, such as calcification or prosthetic heart valves, create large acoustic shadowing effects behind which obtaining an ultrasound signal is difficult if not impossible. For this reason transesophageal echocardiography represents a new essential window into the heart. By positioning a transducer mounted on a fibroscopy sheath into the esophagus in close contact with the left atrium, images of unequaled quality are obtained. An image-resolution of the order of 1-2 mm explains the diagnostic quality in infectious aortic and mitral valve diseases for assessing small vegetations, annular abscesses, and regurgitant lesions by adding color-coded Doppler. The investigation of prosthetic valves dysfunction is completely renewed for detecting disinsertion and thromboses. Heart screening for systemic emboli includes mandatory how the visualization of left (and also right) auricles and the interatrial septum associated with contrast study. Lesions of the descending aorta (aneurysms, thromboses and especially dissections) are perfectly documented in combination with color-Doppler indicating true and false channels as well as re-entry sites. Lastly, other applications are being developed including global and segmental myocardial contractility at rest or even at stress, although this last application is still at the experimental stage. Transesophageal echocardiography therefore appears to constitute a real revolution as an added possibility to the cardiological use of ultrasound: the indication for this "window" being decided for the preferential cases described above only after having performed a standard echo examination. Very often, the indication will be raised by the echocardiographer who, after performing a conventional echo may consider that better or supplementary information could be obtained via the esophageal route. This technique performed by trained operators, is relatively simple, minimally traumatic and can be performed on an outpatient basis provided certain precautions, imposed by the preparation and the consequences of premedication received by the patient, are respected. PMID- 2589813 TI - [Coronary atherectomy using a Rotablator]. AB - A system or rotary atherectomy (Rotablator) was evaluated on coronary stenoses in Man. This device consists of catheter presenting an abrasive olive-shaped knob at one end, and sliding over a central metallic guide, rotating at more than 150,000 tpm. This drill liquifies the atheroma in small microparticles able to cross the microcirculation. The atherectomy surface is perfectly smooth and the risk of thrombosis is minimum. The atherectomy technique is quite simple, similar to PTCA, the balloon being replaced by a drill with a diameter ranging from 1.25 to 2 mm. 48 stenoses in 45 patients were treated with this technique. Twice, the Rotablator's guide was unable to cross the stenosis. In other cases, the stenosis was decreased, in an average, by 75 p. cent (SD 24%) to 43 p. cent (SD 20%) (p less than 0.001). The segment treated is characterized by smooth, linear edges without parictal minithrombi. Complications are most unusual (no deaths, no extended infarction, no emergency bypass related an early reobstruction). The coronary artery may react to the passage of the Rotablator by a spasm; this coronary spasm disappears (sometimes in a few hours) under nitrates derivatives perfusion. The middle term results are very encouraging; in fact, in 19 patients who underwent a control coronary angiography 3 months later, 3 (15%) presented a stenosis. In conclusion, rotary angioplasty is an easy, effective and harmless technique. The exact percentage of re-stenosis remains to be specified in larger series. PMID- 2589812 TI - [Hemodynamic effects of perindopril]. AB - 1. The effects of prolonged infusion of perindopril (1 mg/kg/d) were studied on Goldblatt rats and spontaneously hypertensive SHR rats compared to control animals. Perindopril increased significantly the arterial compliance in treated animals. Mechanical parameters of the carotid artery are normalized with perindopril infusion in renovascular hypertensive rats and improved in SHR rats. Perindopril reversed the thickness of aortic media in treated rats. After three months treatment the ratio elastine/collagen of the aortic media increased significantly. Perindopril reversed the majority of vascular alteration in both hypertensive groups. 2. Twenty one hypertensive patients received for 30 minutes an infusion of perindoprilat either at 1 mg/kg/min, or at 2.5 mg/kg/min, or dihydralazine at 4 mg/kg/min. It was shown that perindoprilat significantly reduced the blood pressure in the three groups. However the increase in arterial diameter and compliance were only recorded with perindoprilat (2.5 mg/kg/min) infusion. The results of this study pointed out that for the same antihypertensive effect, with two different antihypertensive drugs, the vascular effects can be different. Blood pressure, forearm hemodynamic parameters, echocardiography values were recorded on 16 sustained hypertensive patients before and after one year of perindopril treatment. The results showed that perindopril decreased significantly the SBP, DBP and the MBP, increased diameter and arterial compliance of the brachial artery, and decreased cardiac mass. Three months later, the treatment was stopped for four weeks: blood pressure and hemodynamic values returned toward basal values, whereas mass cardiac didn't increase significantly; then the treatment was continued over 9 months; during this period. The arterial compliance increased again on the cardiac mass remained reduced. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2589814 TI - Modern trends in urology. PMID- 2589815 TI - Migration within the island of Korcula, Yugoslavia. AB - For several centuries the village populations on the Yugoslav island of Korcula have remained essentially isolated from each other and from the mainland. Historical, linguistic and biological data indicate that systematic population pressure predominantly came from the coastal area of the Balkan peninsula westward onto the island. To examine short and long range migration on the island, data on the place of birth of parents of adult inhabitants (1168 subjects) were presented and migration matrices analysed applying a gamma function. Most examinees were born in the same village as their parents (86.39%); only 6.33% of the parents migrated between villages on the island; and village endogamy is quite high for the past four generations (75%). When inter-village migration has occurred, migration density is greatest at a distance of 8-12 km, rather than from the immediate neighbourhood. Short range migration occurs up to a mean distance of 33.98 km, long range migration over distances greater than 28 km. PMID- 2589816 TI - Body circumferences as alternatives to skinfold measures of body fat distribution in children. AB - The ratios of circumferences (waist/hip, waist/thigh) have been proposed in lieu of skinfold measurements for studies of obesity and body fat distribution in adults. The skinfold method has been used successfully in children to study the growth and development of patterns of body fat distribution, but circumferences have not. We studied the relationship between these two methodologies as indicators of body fat and its anatomical distribution among 365 normal children aged 6-11 years, using canonical correlation analysis. With this method, weighted vectors of four body circumferences on the one hand and five skinfolds on the other are formed in such a way that the correlation between the two sets of variables is maximized. Weights (regression coefficients) are assigned each variable and their strength and sign help us to select the best combination of circumferences which describe a component of centralised obesity. A first canonical correlation was substantial in both boys and girls (0.84) and was independent of age. It appeared to relate to fatness level. A second canonical correlation was low (0.34 in boys, 0.35 in girls) (p less than 0.01). It too was age independent and in both sexes it reflected differences between fat on the trunk and on the lower extremity, and was thus a component of centralised fat distribution. The simple waist/thigh ratio correlated better with this canonical variable (0.67-0.88) than the more commonly used waist/hip ratio (0.45-0.79). The 'best' index of centralised fat in children is therefore, the waist/thigh circumference ratio, the same one that has been suggested for adults. PMID- 2589817 TI - The growth of Melanesian and Indian children in Fiji. AB - A cross-sectional study was made of the growth of Melanesian and Indian children residing in or near Suva, the capital of Fiji. Melanesians numbered 283 males and 269 females, Indians 201 males and 216 females. Melanesian ages ranged from 6 to 20; Indian from 6 to 15. Generally Melanesians were larger than Indians at all ages and the most significant discriminating measurements were calf circumference and nose breadth for males, and face height and nose breadth for females. The most significant shape indexes were nasal index, ponderal index and relative sitting height, with Melanesians having relatively broader noses and less linear build. Puberty indicators (breast development, age at menarche) showed Indians to be significantly in advance of Melanesians with the exception of age at B2. In particular menarche was earlier by approximately two years. With a median value of 11.80, Indian menarcheal age appeared to be extremely low. Socioeconomic factors (social class, sibship size, position in sibship) appeared to have a comparatively small effect on growth in the two populations, the exception being age at menarche, which was greater among lower social status children, but earlier in girls from larger families. There was evidence for a secular trend to greater size among Melanesians over the last 15-20 years, but little evidence of a trend during 1930-70. However, the differences between the samples used necessitate caution in the interpretation of the data. PMID- 2589818 TI - Variation in adult body dimensions in relation to economic condition among the Mahishyas of Howrah district, West Bengal, India. AB - The body dimensions of adults in three economic subgroups of the Mahishya caste population of Chakpota village, Howrah district, West Bengal, India, were studied. In both sexes, with the decline in economic condition values of body size measurements, skinfold thickness, body fat and anthropometric indices decrease, with the exception of the ponderal index, the value of which increases. The sex difference in height increases with increasing economic status. The correlation between weight and height is highest in the low economic subgroups. PMID- 2589819 TI - Estimates of historical migration in County Durham. AB - Twelve parishes in Northumberland and County Durham were used to estimate the accuracy of Anglican marriage registers as indicators of migration between birthplace and marriage. We compared entries in the marriage registers with the annotated baptismal registers which exist for most Northumberland parishes from 1798-1812, and which explicitly document the birthplaces of the parents of the child baptised. By linking individual marriages and subsequent baptisms we showed that the marriage registers systematically underestimate the amount of migration, with values of f (predicted by Wright's Island model) estimated from marriage registers likely to be two to four times the size of those indicated by the baptism registers. PMID- 2589820 TI - The distribution of age at menarche in a random series of Turin girls followed longitudinally. AB - A longitudinal study on 508 girls chosen at random from the elementary schools of Turin showed that age at menarche had a Gaussian distribution. The mean age was 12.58 +/- 0.05 years. Peaks of incidence of menarche were observed in January and July-September. The correlation coefficient of mothers' (recollected) age at menarche with daughters' was 0.32. PMID- 2589821 TI - Factors influencing the growth of Bahraini school-children. PMID- 2589822 TI - Expression of selected genes and oncogenes in differentiated HL-60 cells and primary cells from human leukemias. AB - cDNA clones complementary to mRNA of cells from patients with chronic lymphocytic leukemia (CLL) were used to examine quantitative changes in the mRNA levels of specific genes in human leukemia leukocytes. Twenty one CLL-positive clones that did not hybridize with placental mRNA were studied. These clones were significantly represented in the mRNA from leukemic leukocytes and were not represent in the mRNA from normal leukocytes. There was high level of expression of 7-2D gene in CLL and B lymphoma cells. RNA hybridizing with clone 7-3G was comparatively highly abundant in CCRF-CEM and EB virus transformed lymphoid cell, while clone 6-1E was highly represented in the mRNAs of Molt 3 and CCRF-CEM cells. The expression of three clones (6-1E, 7-3G and 9-5C) selected from a CLL cDNA library was studied by nucleic acid hybridization in human promyelocytic leukemia cell (HL-60) treated with chemical inducers of cell differentiation. The differentiation of HL-60 cells into macrophage-like cells upon induction by 12-o tetradecanoylphorbol-13-acetate (TPA) was accompanied by rapid induction of the expression of 6-1E and 7-3G genes. The levels of expression of the 9-5C gene were not altered during macrophage-monocytic or granulocytic differentiation of HL-60 cells. The expression of the 6-1E and/or 7-3G gene was induced by TPA in four of 6 samples derived from patients who achieved complete remission, but not in any of the acute nonlymphocytic leukemia samples from patients who failed to achieve complete remission. These findings suggest that expression of the 6-1E and 7-3G genes is related to macrophage-monocytic differentiation and that alterations of these gene expressions in fresh leukemic cells after one hour of TPA treatment are of prognostic significance in predicting the response to treatment. The primary structure of a cDNA of a gene (6-1E) selectively expressed in CLL was determined. A computer search in the nucleotide sequence data bank did not identify this gene as any other gene. The 677 nucleotide mRNA is composed of a 384 nucleotide pol A tail. Moreover, the sequences of the other cDNA clones (1 6G, 5-2C,5-5G, 6-1G, 7-3G, 7-4A, 8-6G, and 9-5C) are not present in those of the data base of GenBank recorded up to 1988.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2589823 TI - Nuclear DNA content and nuclear atypia. Relation to survival in patients with breast adenocarcinoma and serious ovarian tumors. AB - The grade of nuclear atypia (low, medium, or high) was compared with DNA content in 122 tumors comprising 73 serous ovarian tumors and 49 mammary carcinomas of ductal type. The study was performed on two consecutive histologic sections 4 mu in thickness, one of which was stained with hematoxylin-eosin for estimation of nuclear atypia, and the other with Feulgen for measurements of DNA. In both tumor groups there was a significant correlation between nuclear atypia and nuclear DNA content. The results suggest that DNA analysis is of significant additional prognostic value even when the grade of nuclear atypia is known. PMID- 2589824 TI - New synthetic retinoids: effects on proliferation and differentiation. AB - Nine retinoid analogues were synthesized and their effects on cell proliferation and differentiation of tumor cell lines were analysed and compared with those of natural retinoids (retinoic acid, retinol, retinal). Our results demonstrate differential inhibitory effects of the synthetic retinoids on cell growth. This inhibitory activity of the synthetic retinoids was, in some cases, higher than that of retinoic acid and retinol. Natural and synthetic retinoids were found to be able to induce to a different extent erythroid differentiation of murine erythroleukemia cells and adipogenic conversion of Chinese Hamster FHO6N1-1 cells. Our data suggest that studies on the relationship between structure and biological activity could be approached by using the analysed synthetic retinoids. PMID- 2589825 TI - [The course of 203 superficial urothelial malignant tumors of the bladder during conservative treatment]. AB - The authors present a total of 203 patients with histologically proven superficial bladder transitional cell cancer. Patients without recurrence had a follow-up longer than 12 months. The mean follow-up from the time of diagnosis was 35 months +/- 27 (standard deviation). Transurethral resection was not systematically followed by intravesical therapy. The following drugs were used: thiotepa, doxorubicin, BCG and rarely mitomycin C. Although BCG was generally used after failure of thiotepa or doxorubicin, it achieved the best results. 13 patients had a total cystectomy (6.4%). Patients without complete remission had a higher percentage of high grade and stage T1 tumors than patients without recurrence (the difference was statistically significant). The same applied to mortality: it was statistically more frequent in the first group than in the second group of patients. PMID- 2589826 TI - [Magnetic resonance imaging of cancer of the prostate. Preliminary study]. AB - Twenty-two patients with prostatic carcinoma have been studied by magnetic resonance imaging (MRI). Twenty-three examinations have been done for 2 stage A, 11 stage B, 2 stage C and 7 stage D. Prostatic signal and locoregional extension have been compared with rectal examination and the 3 prostatectomies. Cancer looked homogeneous in 4 cases, heterogeneous in 10 cases with a nodule in 5 cases either with hyper of hyposignal compared to the normal prostate. Local extension in stages C and D is seen, especially to the periprostatic fat and seminal vesicles. MRI appears to be sensitive but poorly specific in the diagnosis of prostatic cancer. On the other hand, it is an interesting examination in the staging of prostatic cancer. These results must be confirmed with more comparisons of images and prostatectomy specimens. PMID- 2589827 TI - [Rectal stenoses caused by carcinoma of the prostate. Apropos of 9 cases]. AB - Rectal strictures are rare complications of prostatic cancer and are considered to be a sign of poor prognosis. The authors report 9 cases. In 5 cases, the cancer was already diagnosed and had been treated by endocrine therapy. All patients died during the months following onset of the intestinal symptoms despite diversion colostomy (4 cases) and high dose oestrogen therapy. Rectal strictures therefore have the same poor prognosis as escape from endocrine therapy. In 3 cases, the stricture was the presenting sign of the cancer in one case, the cancer was already known and treated by radiotherapy; in this case, survival depends on the hormone sensitivity of the cancer and one patient survived for 7 years with subsequent closure of the colostomy. PMID- 2589828 TI - Fertilization of human oocytes in capillary tubes using very low number of spermatozoa. A new treatment of severe oligozoospermia? AB - In this study a culture system was developed in which successful fertilization was performed in capillary tubes (75 x 0.9 mm) using very low numbers of spermatozoa. Oocytes were fertilized in 5-10 microliters medium containing 500 4,000 sperms (0.1-0.4 Mill. sperms/ml). In 10 IVF-patients with normozoospermia a total of 64 oocytes were cultured in capillaries and in tissue culture tubes (1 ml medium, 0.1 Mill. sperms/ml). The fertilization rate in tubes was 78% (25/32) and in capillaries using 4,000, 2,000, 1,000 and 500 sperms/oocyte: 71% (5/7), 86% (6/7), 60% (6/10) and 50% (4/8), respectively. The fertilization rate of mature oocytes was higher compared to immature oocytes (tubes: 83% vs 63%) capillaries: 74% vs 44%). Fertilization in capillaries using a volume of 10 microliters compared to 5 microliters seems to provide better culture conditions (fertilization rate: 75% vs 62.5%) cleavage rate: 91% vs 60%). The capillary technique may also provide a new treatment of severe oligozoospermia or in cases of poor sperm recovery after sperm preparation for IVF since in 3 patients with poor quality semen (total motile sperm/ejaculate: 0.2-1.4 Mill.) fertilization, cleavage and 1 pregnancy resulted. These preliminary results indicate the usefulness of capillary technique if standard IVF systems fail or before semen donation or sperm microinjection are anticipated. PMID- 2589829 TI - The pull-through technique for the advancement of the unfolded epididymal tubule and the tubulo-deferential telescopic reconstruction. AB - A new reconstructive microsurgical model of the epididymo-deferential complex was performed in the rat to study the plastic adaptation of the distal epididymal tubule in transposition and/or substitution procedures. The model consists of three steps: endoluminal stripping of the mucosa of the proximal half of the vas deferens; pull-through technique for the advancement of the unfolded epididymal tubule of the "zone 9" into the stripped vas deferens; end-to-end tubulo deferential telescopic reconstruction. PMID- 2589830 TI - [Microanatomy of the female urethra]. AB - The author presents a description of the microscopic anatomy of the bladder neck and female urethra based on reconstructions derived from microscopic sections performed in 3 planes. He describes the horizontal and vertical fibres. The horizontal fibres form 2 opposed, arched layers encircling the upper part of the bladder neck and derived from the detrusor. Inferiorly, there is a very small, annular, smooth muscle sphincter which surrounds the middle part of the urethra like a cuff. The vertical fibres arise from the detrusor mostly terminate in the periphery of the circular fibres. Several fibres also pass in the urethral lumen. PMID- 2589831 TI - [Urethral compliance in the elderly female]. PMID- 2589832 TI - [Urethral stenosis and urinary incontinence in the female. 149 cases]. PMID- 2589833 TI - [Urethritis cause by round-form Trichomonas in women]. PMID- 2589834 TI - [Urethral meatus and cystitis]. PMID- 2589835 TI - [Results of the Rieser intervention in the prevention of recurrent cystitis of the female in 34 cases]. PMID- 2589836 TI - [Surgical treatment of urethral diverticula. Retrospective critical study: value of surgery in the ventral-decubital position]. PMID- 2589837 TI - [Tumors of the female urethra]. PMID- 2589838 TI - Evidence of differential growth in the human skull from sagittal and transversal deviations of landmarks. AB - The differences in position along, and deviations from the midline of six landmarks on the base and face of 51 recent skulls of recorded sex and age from Middle Europe were studied. There is accordance between the average anatomical position of the landmarks and their mean vertical distances from the line connecting the two poria. The majority of the specimens show deviations from the midline predominantly towards the left half of the skull. Variation of the landmarks is discussed with respect to differing growth processes and with respect to the frequently asymmetric location of the two poria cited in the literature. PMID- 2589839 TI - Discontinuous traits of the skull: variations on sex, age, laterality. AB - This paper discusses some problems relating to the study and the utilization of discontinuous traits in anthropology. The importance of sex, age and laterality in the manifestation of these traits is discussed on the basis of investigations on a numerous skeletal sample of Siena (Tuscany, Italy) and on data from literature. It is pointed out that sides and sexes should be considered separately. The age of adult subjects seems to be insignificant as the incidence of these traits is concerned. PMID- 2589840 TI - Purification and characterization of an antibacterial substance produced by a marine Alteromonas species. AB - An extracellular inhibitory substance produced by the marine Alteromonas strain P 31 (NCMB 2144) was isolated and purified. The inhibitor was a macromolecule with a molecular weight of 90,000 estimated by Sephadex G-100 chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The inhibitory activity was antagonized by proteinase K and beta-amylase and inactivated by heating at 80 degrees C for 30 min. The purified substance exhibited two typical absorption bands in the infrared spectrum at 1,650 and 1,075 cm-1, corresponding to peptide linkages and carbohydrate residues, respectively. These findings allowed us to characterize the antimicrobial compound as a thermolabile glycoprotein. The substance exhibited a broad inhibitory spectrum, being active against clinical and environmental isolates from related and nonrelated taxonomical bacterial groups as well as against the producer strain and other similar marine bacterial strains. The inhibitory glycoprotein did not display cytotoxicity toward mammalian and fish cell lines. PMID- 2589841 TI - Concentrations of ofloxacin in serum and cerebrospinal fluid of patients without meningitis receiving the drug intravenously and orally. AB - The cerebrospinal fluid (CSF) penetration of ofloxacin given orally or or intravenously was studied in cancer patients without meningitis. Each patient was assigned to a different sampling time to assess the relation between time and penetration. Ofloxacin was measured in serum and CSF by high-pressure liquid chromatography and bioassay. In addition, the bactericidal titers were measured in CSF and serum against a set of relevant bacteria. Concentrations measured by high-pressure liquid chromatography and bioassay were well correlated. Peak concentrations in CSF (0.4 to 1 microgram/ml) were observed 2 to 4 h after infusion or oral administration. Peak concentrations in serum were observed just after infusion (2 to 3.5 micrograms/ml) or 1 to 2 h after oral administration (1.7 to 4 micrograms/ml). Measured bactericidal titers were well correlated with the titers expected from the MBC and concentration. High CSF bactericidal titers were observed against Neisseria meningitidis, Haemophilus influenzae, and Escherichia coli, whereas low or no bactericidal titers were obtained against Staphylococcus aureus, Listeria monocytogenes, and Streptococcus pneumoniae. PMID- 2589842 TI - In vitro effects of three new 1,2,4-trioxanes (pentatroxane, thiahexatroxane, and hexatroxanone) on Toxoplasma gondii. AB - The in vitro effects of three synthetic, cis-fused, bicyclic 1,2,4-trioxanes (pentatroxane, thiahexatroxane, and hexatroxanone) against intracellular Toxoplasma gondii were studied. Unactivated peritoneal macrophages were infected with the virulent RH strain of T. gondii and exposed to the 1,2,4-trioxanes at different concentrations. The antitoxoplasmic activity of the drugs was first assessed with [3H]uracil, which is incorporated by the parasite but not the host cell. Pentatroxane and thiahexatroxane were the most active, exhibiting 90% inhibitory concentrations of 6.8 and 5.3 micrograms/ml, respectively. Furthermore, microscopic examination of the infected macrophages after treatment with pentatroxane, thiahexatroxane, and hexatroxanone at their respective 90% inhibitory concentrations confirmed the inhibition of intracellular growth of T. gondii. Their activities were comparable to those of pyrimethamine (1 micrograms/ml) and pyrimethamine (0.1 micrograms/ml) in combination with sulfadiazine (25 micrograms/ml). Pentatroxane and thiahexatroxane were also able to inhibit intracellular growth of T. gondii within nonprofessional phagocytes (HeLa cells), suggesting that the antitoxoplasmic activity was not caused by a macrophage-specific mechanism, such as macrophage activation. However, the 1,2,4 trioxanes were not active against extracellular T. gondii. Pentatroxane and thiahexatroxane are new, promising compounds that deserve further study to assess their usefulness for treating toxoplasmosis. PMID- 2589843 TI - Comparative evaluation of cefazolin and clindamycin in the treatment of experimental Staphylococcus aureus osteomyelitis in rabbits. AB - A rabbit model for Staphylococcus aureus osteomyelitis was used to compare treatment with clindamycin and cefazolin. Cefazolin (5 mg/kg), cefazolin (15 mg/kg), and clindamycin (70 mg/kg) were injected subcutaneously every 6 h for 28 days. After treatment, S. aureus was found in bone cultures from 22 of 23 control rabbits, 12 of 22 rabbits treated with cefazolin (5 mg/kg), 12 of 23 rabbits treated with cefazolin (15 mg/kg), and 2 of 20 rabbits treated with clindamycin. Drug concentrations in serum, uninfected bone, and infected bone were measured 30 min after cefazolin or clindamycin was injected into a group of rabbits which had been infected for 3 to 4 weeks. Clindamycin gave the highest concentration in infected and uninfected bone. The results of the study showed that clindamycin was superior to cefazolin in the eradication of S. aureus from infected bone in an experimental model. PMID- 2589844 TI - Selection of an oral prodrug (BRL 42810; famciclovir) for the antiherpesvirus agent BRL 39123 [9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine; penciclovir]. AB - The limited oral absorption in rodents of the antiherpesvirus agent 9-(4-hydroxy 3-hydroxymethylbut-l-yl)guanine (BRL 39123 [penciclovir; British approved name]) prompted a search for oral prodrugs. The 6-deoxy derivative of penciclovir (BRL 42359) and the corresponding diacetyl and dipropionyl 6-deoxy derivatives (BRL 42810 [famciclovir; British approved name] and BRL 43599) were tested as oral prodrugs. The in vivo absorption (dose, 0.2 mmol/kg) and the conversion to the active compound, penciclovir, were determined in rats. Compared with the sodium salt of penciclovir given intravenously, the bioavailabilities of penciclovir from orally administered penciclovir, BRL 42359, famciclovir, and BRL 43599 were 1.5, 9, 41, and 27%, respectively. These prodrugs and 6-deoxyacyclovir were tested for stability in rat duodenal contents and for metabolism in rat intestinal wall homogenate, liver homogenate, and blood and in the corresponding human fluids and tissues. Famciclovir was much more stable than BRL 43599 in human duodenal contents (half-lives, greater than 2 h and 7 min, respectively) yet was efficiently converted to penciclovir by the tissue homogenates. The major metabolic pathway was by deacetylation followed by oxidation at the 6 position. The rate of oxidation was comparable to that of 6-deoxyacyclovir, which is known to be converted efficiently to acyclovir in humans. Famciclovir was selected for further evaluation and progression to studies in humans. These subsequent studies confirmed that, after oral dosing with famciclovir, more than half the dose was absorbed and rapidly converted to penciclovir. PMID- 2589845 TI - Comparative in vitro activity and beta-lactamase stability of FK482, a new oral cephalosporin. AB - FK482 is an oral aminothiazolyl hydroxyimino cephalosporin with a C-3 vinyl group. Its activity was compared with those of cephalexin, cefuroxime, cefixime, and amoxicillin-clavulanate. FK482 inhibited 90% of Staphylococcus aureus isolates at 1 micrograms/ml and 90% of Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus pneumoniae isolates at less than or equal to 0.012 micrograms/ml, superior to cephalexin and cefuroxime and similar to cefixime. It did not inhibit oxacillin-resistant S. aureus. FK482 inhibited 90% of Enterococcus faecalis isolates at 8 micrograms/ml. Although 90% of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella species, and Shigella species isolates were inhibited by less than or equal to 2 micrograms/ml, FK482 was less active than cefixime against Citrobacter, Enterobacter, Morganella, Serratia, and Providencia species, with MICs for many isolates of greater than 8 micrograms/ml. FK482 inhibited Haemophilus influenzae and Neisseria gonorrhoeae at concentrations comparable to that of cefixime and superior to those of cephalexin and cfaclor. Bacteroides and Pseudomonas species were resistant. FK482 was not hydrolyzed by the TEM-1 and TEM-2 beta-lactamases but was hydrolyzed by TEM-3 and the Proteus vulgaris enzyme. It had a high affinity for chromosomal beta-lactamases. PMID- 2589846 TI - Bioequivalence assessment of zidovudine (Retrovir) syrup, solution, and capsule formulations in patients infected with human immunodeficiency virus. AB - The objectives of this open-labeled, multiple-dose, three-way-crossover trial were to evaluate the safety and tolerance of zidovudine (Retrovir) oral syrup and to assess the bioequivalence of this formulation relative to zidovudine solution and capsule formulations in human immunodeficiency virus-infected patients. Over the 7-day study, 12 adult male subjects received 12 administrations each of the capsule, solution, and syrup formulations every 4 h (six times daily) in a randomized sequence. Frequent blood samples were collected over the 4-h period after dose 12 was administered. Zidovudine concentrations in plasma were determined by a specific and sensitive radioimmunoassay. Results from statistical analyses indicated that all three formulations were bioequivalent with respect to systemic availability (area under the time-concentration curve) and that the syrup was also equivalent to the solution with respect to the maximum peak concentration in serum. The lower relative maximum peak concentration in serum (approximately 81%) and small delays in time to peak concentration (less than 30 min) of the capsule formulation as compared with the liquid formulations are thought to be due to the additional processes of disintegration and dissolution associated with capsule administration. All three preparations were well tolerated during the 7-day study. PMID- 2589847 TI - Combination effect of recombinant human interleukin-1 alpha with antimicrobial agents. AB - Combination effects of recombinant human interleukin-1 alpha with ceftazidime, moxalactam, gentamicin, enoxacin, amphotericin B, miconazole, or an immunoglobulin preparation were evaluated in systemic infections with Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans in normal mice and systemic infection with P. aeruginosa in mice with leukopenia induced by preadministration of cyclophosphamide. Synergistic effects were generally observed at interleukin-1 alpha doses as low as 1 to 30 ng per mouse with most combinations. The results show the possibility that recombinant human interleukin 1 alpha could be of help for treating obstinate infections not successfully treated with antimicrobial agents alone. PMID- 2589848 TI - Treatment of experimental disseminated candidiasis with cilofungin. AB - The efficacy of cilofungin treatment of experimental disseminated candidiasis in rabbits was examined. Cilofungin treatment reduced yeast counts, especially in the kidney, with activity comparable to that of amphotericin B. The peak level of cilofungin in serum was measured at 5 min after administration of a single dose, with no drug detectable after 90 min. PMID- 2589849 TI - Distribution of clinically important thermophilic actinomycetes in vegetable substrates and soil in north-western India. AB - Medically important thermophilic actinomycetes were isolated from 218 (64%) of 341 samples of vegetable substrates and soil examined from sites in north-western India. Thermoactinomyces vulgaris (T. candidus) was the commonest species, occurring in 56% of samples, followed by Saccharomonospora viridis in 29%, Thermoactinomyces thalpophilus in 27%, Faenia rectivirgula (Micropolyspora faeni) in 21% and Thermoactinomyces sacchari in 14%. T. vulgaris and T. thalpophilus were isolated from all types of substrate examined, with T. vulgaris always more common than T. thalpophilus. Of the other thermophilic actinomycetes, F. rectivirgula was isolated predominantly from hay (44%) and S. viridis (56%) and T. sacchari (44%) from sugar-cane bagasse. The largest populations of T. vulgaris and T. thalpophilus were found in paddy straw, followed by T. sacchari, S. viridis and F. rectivirgula in sugar-cane bagasse. The widespread occurrence of these clinically important thermophilic actinomycetes suggests that exposure of humans and animals to them may be frequent in north-western India. Studies are required to determine the prevalence of extrinsic allergic alveolitis (hypersensitivity pneumonitis) caused by thermophilic actinomycetes in the local population. PMID- 2589850 TI - Nitrogen metabolism in the facultative methylotroph Arthrobacter P1 grown with various amines or ammonia as nitrogen sources. AB - The metabolism of trimethylamine (TMA) and dimethylamine (DMA) in Arthrobacter P1 involved the enzymes TMA monooxygenase and trimethylamine-N-oxide (TMA-NO) demethylase, and DMA monooxygenase, respectively. The methylamine and formaldehyde produced were further metabolized via a primary amine oxidase and the ribulose monophosphate (RuMP) cycle. The amine oxidase showed activity with various aliphatic primary amines and benzylamine. The organism was able to use methylamine, ethylamine and propylamine as carbon- and nitrogen sources for growth. Butylamine and benzylamine only functioned as nitrogen sources. Growth on glucose with ethylamine, propylamine, butylamine and benzylamine resulted in accumulation of the respective aldehydes. In case of ethylamine and propylamine this was due to repression by glucose of the synthesis of the aldehyde dehydrogenase(s) required for their further metabolism. Growth on glucose/methylamine did not result in repression of the RuMP cycle enzyme hexulose-6-phosphate synthase (HPS). High levels of this enzyme were present in the cells and as a result formaldehyde did not accumulate. Ammonia assimilation in Arthrobacter P1 involved NADP-dependent glutamate dehydrogenase (GDH), NAD dependent alanine dehydrogenase (ADH) and glutamine synthetase (GS) as key enzymes. In batch cultures both GDH and GS displayed highest levels during growth on acetate with methylamine as the nitrogen source. A further increase in the levels of GS, but not GDH, was observed under ammonia-limited growth conditions in continuous cultures with acetate or glucose as carbon sources. PMID- 2589851 TI - Debaryomyces udenii, sp. nov. (Saccharomycetaceae), a new species from soil. AB - A new, soil-associated species of the genus Debaryomyces, D. udenii, is described. The species is characterized by pusticulate rather than verrucate ascospores, and slowly lytic asci. PMID- 2589852 TI - Occurrence and metabolic significance of microbodies in trophic hyphae of the nematophagous fungus Arthrobotrys oligospora. AB - This paper describes the results of an ultrastructural study on the subcellular events occurring in nematode-infecting (trophic) hyphae of the nematophagous fungus Arthrobotrys oligospora. In early stages of the infection process (30 min 4 h), the infection bulb and developing trophic hyphae are characterized by a highly proliferated endoplasmic reticulum (ER). Its membranes often appeared vesiculated and occur in close association with the cell membrane of the cells. Upon further invasion of the nematode, lipid droplets developed in the trophic hyphae; these droplets were first observed 4-5 h after the infection but were abundantly present after 24-36 h. Along with the formation of lipid droplets proliferation of microbodies was observed. These organeles were characterized by the presence of catalase and thiolase and were frequently observed in close association with the lipid droplets. Later on the lipid droplets disappeared. During this period new vegetative mycelium developed from the trap that had originally captured the nematode. Our results suggest that part of the nutrients released from the nematode are first converted into lipids by the fungus which in turn are degraded via the beta-oxidation pathway and further metabolized to support growth of new vegetative hyphae. PMID- 2589853 TI - Significance of electron dense microbodies in trap cells of the nematophagous fungus Arthrobotrys oligospora. AB - We have studied the fate of electron dense microbodies in nematode-trapping organs (traps) of the fungus A. oligospora during the initial hours following nematode capture. The interaction studies were performed with isolated traps which had captured a nematode under conditions where the fungal cells had no access to external energy sources. Video enhanced contrast microscopy showed that under these conditions the number of dense bodies present in the trap cell that formed the penetration tube, rapidly decreased. During subsequent penetration and development of the infection bulb this decrease continued while at this time common cell organelles such as mitochondria and vacuoles were formed. This was confirmed by electron microscopy which also revealed that the dense bodies were degraded by means of an autophagic process. The organelles were degraded individually and finally turned into compartments which, based on ultrastructural criteria, were considered vacuoles. Fusion of such vacuoles into larger organelles frequently occurred. The degradation process was initiated early in the interaction since initial stages were already evident within 15 min after capture. Generally it took 1-2 h before the infection bulb had fully developed and trophic hyphae formation started. During this time the original trap cell, characterized by numerous dense bodies, was transformed into an active vegetative hyphal cell containing typical cell organelles such as nuclei, mitochondria, a strongly proliferated endoplasmic reticulum, vacuoles and "normal" microbodies but lacked dense bodies. This disappearance of dense bodies was confined to the cell that penetrated the nematode and--less frequently--its two neighbouring cells in the hyphal loop. In the other cells, constituting the trap, the dense bodies remained unaffected. As will be discussed, the present results support our current view that traps of A. oligospora contribute to the survival of the organism in its natural environment. PMID- 2589854 TI - Purification and characterization of bacteriophage receptor on Veillonella rodentium cells. Phage-receptor on Veillonella. AB - Veillonellophage N2 adsorbed to polysaccharides (PSs) on Veillonella rodentium ATCC 17743 cell wall, and the bacteriophage receptor contained only glucosamine. D(+)-glucosamine hydrochloride (Sigma) also adsorbed the veillonellophage N2. These results therefore indicate that the receptor to the veillonellophage N2 is cell wall PSs. The PSs of the host cells as receptor have been characterized. Glucosamine accounted for approximately 100% of the weight of the PSs. The PSs which were partially resolved by Sephadex G-75 chromatography comprised approximately four glucosamine units. Their primary structure was determined by 400 MHz n.m.r. spectroscopy. One- and two-dimensional 1H-nmr experiments showed the PS to be a branched polymer. Glucosamine linkage was detected in one of the branches. PMID- 2589855 TI - Zygozyma suomiensis, sp. nov. (Lipomycetaceae), a new species from Finland. AB - A new species of the genus Zygozyma, Z. suomiensis, is described, based on the study of a single strain, derived from a bovine skin lesion. PMID- 2589856 TI - Low-dose alternate-day prednisone for persistent Wells' syndrome. PMID- 2589857 TI - Physical properties of aerosols produced by dermabrasion. AB - Medical personnel who perform dermabrasions are exposed to airborne blood and tissue fragments. The safety or hazards of exposure to such aerosols have not been adequately studied. Using scanning electron microscopy, the air density and size distribution of particles produced during dermabrasion were analyzed. Such particles are of sufficient size to allow for access to and retention by mucosal and pulmonary surfaces. Transmission electron microscopy reveals amorphous particles without discernible cell membranes. Commonly used personnel protection standards do not prevent respiration of these particulates. Mathematical estimation of particle size production allows extrapolation of these data to other rotary instrument applications. PMID- 2589858 TI - Routine screening for syphilis is justified in patients admitted to psychiatric, alcohol, and drug rehabilitation wards of the Veterans Administration Medical Center. AB - Of 1515 patients admitted to psychiatric, alcohol, and drug rehabilitation services in the Veterans Administration Medical Center, Buffalo, NY, during the year 1987, who were screened by serologic tests for syphilis, 16 (1.05%) had positive rapid plasma reagin and fluorescent treponemal antibody-absorption tests for syphilis. A positive serologic test result was not suspected on clinical grounds in any of these patients. All were detected by routine screening. Of the 16 patients, 15 had charts available for review. Seven patients were treated for primary or late syphilis; four patients had received previous treatment; and four patients had no evaluation of test results and received no treatment. Routine screening of hospitalized patients who are alcohol or drug abusers is justified, but close follow-up is necessary to make screening meaningful. PMID- 2589859 TI - A comparison of the dose-response relationship for psoralen-UVA erythema and UVB erythema. AB - Twenty patients with psoriasis were phototested to determine their erythemal responses to UVB and psoralen-UVA (PUVA) (oral 8-methoxypsoralen). The smallest ultraviolet radiation doses to produce erythema (minimal erythema dose and minimal phototoxic dose, respectively) were recorded and dose-response curves were constructed for UVB (24 hours after irradiation) and PUVA (48 hours) using objective measurement. The choice of a 48-hour measurement was validated by phototesting an additional 11 subjects to determine the time course of PUVA erythema. No correlation was demonstrated between minimal erythema dose for UVB, minimal phototoxic dose for PUVA, and sun-reactive skin type. The mean slope of the dose-response curve for UVB erythema was four times steeper than that for PUVA. Psoralen-UVA erythema reached a broad maximum between 48 and 96 hours after irradiation. Using objective methods we have demonstrated that the commonly accepted view of a steep dose-response relationship for PUVA erythema is not valid. PMID- 2589860 TI - Microbiology of infected epidermal cysts. AB - Specimens from 231 epidermal cyst abscesses were inoculated on media supportive for growth of aerobic and anaerobic bacteria. Of these, 192 yielded bacterial growth. Aerobic or facultative bacteria only were recovered in 84 specimens (44%), anaerobic bacteria only in 57 specimens (30%), and mixed aerobic and anaerobic bacteria in 51 specimens (26%). A total of 315 isolates (162 anaerobes and 153 aerobes) were recovered. An average of 0.8 aerobic or facultative isolates per infected cyst were recovered, and this number was unrelated to the cysts' anatomic sites. However, the number of anaerobic bacteria varied; they were isolated more frequently in perirectal (1.5 isolates per specimen), vulvovaginal (1.4), and head (1.1) infections, and less frequently in trunk (0.7) and extremities (0.4) infections. The predominant aerobic or facultative bacteria were Staphylococcus aureus (81 isolates), group A streptococcus (9 isolates), and Escherichia coli (7 isolates). The predominant anaerobic organisms were Peptostreptococcus species (85 isolates) and Bacteroides species (55 isolates, including 12 Bacteroides melaninogenicus and 9 Bacteroides fragilis groups). The study highlights the polymicrobial nature and predominance of anaerobes in cyst abscesses in the perirectal, vulvovaginal, and head areas. PMID- 2589861 TI - Intrinsic potencies of novel thiol ester corticosteroids RS-85095 and RS-21314 as compared with clobetasol 17-propionate and fluocinonide. AB - The intrinsic potencies of two novel topical thiol ester corticosteroids, RS 85095 and RS-21314, were compared with the high potency corticosteroids clobetasol 17-propionate and fluocinonide, using human vasoconstriction assays. In these assays, four or five concentrations (0.03 to 3 mg/L) of the corticosteroids in 95% ethanol (alcohol, USP) were applied to predetermined sites on the forearm of volunteers and were occluded following evaporation of the alcohol. The responses were scored in terms of the presence or absence of vasoconstriction and the degree of vasoconstrictive intensity. No statistically significant difference was found in the intrinsic potencies of RS-85095, RS 21314, and clobetasol 17-propionate, and all three corticosteroids were significantly more potent than fluocinonide. PMID- 2589862 TI - Extensive nodular secondary syphilis. AB - An indigent male patient presented with a widespread nodular eruption involving the torso and limbs. The differential diagnosis included nodular secondary syphilis, Kaposi's sarcoma, sarcoidosis, and lymphoma. Investigation confirmed secondary syphilis with positive cerebrospinal fluid serologic findings. Penicillin therapy produced a Jarisch-Herxheimer reaction despite pretreatment to diminish this. Discussion on the clinical features and treatment of syphilis is presented. PMID- 2589863 TI - Vulvar lichen planus. AB - The clinical presentation of lichen planus of the vulva spans a spectrum from subtle, fine, reticulate papules to severe erosive disease accompanied by scarring and loss of the normal vulvar architecture. The end result may mimic other diseases. Because cutaneous lichen planus is usually absent and oral disease may be asymptomatic, the diagnosis can be easily missed unless the clinician has a high index of suspicion. Although treatment for vulvar lichen planus is suboptimal, a correct diagnosis may end the patient's search for an answer and help to prevent unnecessary procedures and therapies. PMID- 2589864 TI - Dermal thymus. A light microscopic and immunohistochemical study. AB - Two rare cases of distinctive thymic remnants occurring in the skin are described. The lesions were present at birth, and involved the side of the neck. One child had a complete cleft lip and palate. The other had multiple congenital anomalies consistent with a rare syndrome entitled branchio-oculo-facial syndrome. Microscopically, lobular foci were present in the dermis and consistent with both prethymic and thymic remnants. Immunohistochemical studies using antibodies to T cells and B cells showed a distribution similar to that seen in normal thymus. Dermal thymus appears to be a distinct entity and may be associated with other faciobranchial defects. PMID- 2589865 TI - Skin nodules over the diaper area. Granuloma gluteale infantum. PMID- 2589866 TI - A case of an unusual mole. Combined Spitz Nevus. PMID- 2589867 TI - Effects of oral zinc in erythropoietic protoporphyria. PMID- 2589868 TI - Trichophyton rubrum bullous tinea pedis in a child. PMID- 2589869 TI - Generalized eruptive clear-cell syringoma. PMID- 2589870 TI - Classification of perinatal death. AB - Three paediatric pathologists, one perinatal paediatrician, one obstetrician, and one epidemiologist separately used information collected on 239 babies in an attempt to validate the Wigglesworth classification of perinatal deaths. This was first done using clinical data only, then using the combination of clinical and gross necropsy findings and finally using clinical, gross necropsy, histological and any other information (for example, chromosome analyses, microbiological investigations). Only 14 (6%) of deaths changed groups within the Wigglesworth classification when gross necropsy findings were considered as well as clinical findings, and altogether only 21 (9%) changed classification when complete investigations were available. There was an unacceptable amount (15%) of disagreement between the classifiers, largely the result of failure to comply with the rules laid down for classification. We set out amendments to Wigglesworth's original definitions to clarify certain ambiguities. PMID- 2589871 TI - Carbohydrate fermentation by gut microflora in preterm neonates. AB - To study organic acid excretion, urine was collected from 52 preterm infants at weekly intervals and analysed by capillary gas chromatography-mass spectrometry. Twelve of 22 babies born before 33 weeks' gestation excreted 2,3-butanediol, as did six born between 33 and 36 weeks. Six very immature babies also excreted acetoin, the metabolic precursor of the diol. Other products derived from carbohydrate included methylmalonic and ethylmalonic acids in one baby, and D lactic acid in five. Acetoin has never been found in urine before, and the other four acids have been found only rarely. Excretion of these metabolites by preterm babies can be explained by increased intestinal permeability, unabsorbed lactose in the colon, and colonisation with certain opportunistic micro-organisms prevalent in neonatal units, including klebsiella, serratia, and enterobacter. The findings support evidence from breath hydrogen analysis that carbohydrate fermentation takes place in the gut of preterm infants. PMID- 2589872 TI - Left ventricular output during postnatal circulatory adaptation in healthy infants born at full term. AB - Left ventricular output was measured non-invasively at predefined time intervals from less than 15 minutes to 72 hours after birth in 16 infants who had been born at full term. The blood flow velocity in the ascending aorta was measured by a range gated Doppler technique and multiplied by the cross sectional diameter measured by cross sectional and M mode echocardiography. Left ventricular output remained high in the first two hours, 235-243 ml/min/kg, despite a 10% decrease in heart rate. The fall in heart rate was compensated for by a 15% increase in stroke volume. Between 2 and 24 hours there was a significant fall in mean (SD) left ventricular output to 187 (35) ml/min/kg caused mainly by a reduction in stroke volume. The fall in left ventricle output after two hours may reflect an adaptation to the decreased demand on the left ventricle as the ductus constricts. PMID- 2589873 TI - Chorioamnionitis and serum IgM in Wilson-Mikity syndrome. AB - A total of 753 infants weighing less than 1800 g at birth were studied prospectively and their serum IgM concentrations measured within 72 hours of age. Placentas from 584 of these infants were examined histologically for chorioamnionitis. The results were correlated with chronic respiratory insufficiency. Altogether 101 infants developed chronic respiratory insufficiency of which 22 had bronchopulmonary dysplasia and 35 Wilson-Mikity syndrome. The remaining 44 infants were classified as 'unexplained chronic lung disease'. Mean serum IgM concentration for Wilson-Mikity syndrome was 1.02 g/l whereas it was 0.14 g/l for bronchopulmonary dysplasia and 0.32 g/l for unexplained chronic lung disease. The incidence of chorioamnionitis was significantly higher in Wilson Mikity syndrome (30/35) compared with bronchopulmonary dysplasia (4/16) and with infants without chronic respiratory insufficiency (145/490). Wilson-Mikity syndrome was shown to be significantly correlated with the evidences of intrauterine inflammation. PMID- 2589874 TI - Are preterm infants at risk for subsequent fractures? AB - In Cambridge, between 1979 and 1988, the prevalence of low gestation (less than 37 or less than 33 weeks) was not increased in 362 children under 6 years presenting to casualty with fractures compared with that in 362 children presenting without fractures or in all inborn surviving babies. These data are relevant to the assessment of suspected child abuse after preterm birth. PMID- 2589875 TI - Aneurysm of the ductus arteriosus. AB - Two neonates with aneurysms of the ductus arteriosus were seen. One suffered a fatal spontaneous rupture of the aneurysm, and the second (in which it was an incidental finding) the aneurysm was monitored by echocardiography, and seemed to resolve spontaneously. PMID- 2589876 TI - Ciprofloxacin in neonatal Enterobacter cloacae septicaemia. AB - Multiresistant Enterobacter cloacae infection in six premature infants was eradicated with intravenous ciprofloxacin (10 mg/kg/day). Bacterial resistance did not develop. Adequate plasma ciprofloxacin concentrations were achieved in all treated patients. No clinical evidence of side effects was observed. PMID- 2589877 TI - Fetal ascites: an unusual presentation of Niemann-Pick disease type C. AB - Two infants were seen with severe ascites detected before birth, a previously unreported presentation of Niemann-Pick disease type C. In the second infant no diagnostic storage cells were present in bone marrow. Confirmatory investigations were prompted by experience of the first case. PMID- 2589879 TI - [Proceedings of the Swiss Society of Gynecology and Obstetrics. Annual meeting. Flims, 6-8 April 1989]. PMID- 2589878 TI - Follow up studies: design, organisation, and analysis. PMID- 2589880 TI - [Perinatal infections. Introduction to the topic]. PMID- 2589882 TI - [Osteoporosis]. PMID- 2589881 TI - [Clinical management of premature rupture of fetal membranes]. PMID- 2589883 TI - Time trends in peptic ulcer surgery, 1956 to 1986. A nation-wide survey in Sweden. AB - To establish time trends in surgical rates for peptic ulcer disease, all surgical departments in Sweden were requested to complete a questionnaire regarding elective operations for gastric and duodenal ulcers and emergency operations for ulcer perforations performed in 1956, 1966, 1976, and 1986. A total of 8558 operations were reported for these years. The incidence of elective surgery declined steadily, the rates being 72.1, 45.0, 31.9, and 10.7 per 100,000 inhabitants. The male:female ratio fell from 4.2 to 1.5:1, while the duodenal/gastric ulcer ratio remained virtually unchanged. The operation rate for perforation decreased by 50%, from 12.8 to 6.4 per 100,000 inhabitants. We conclude that there has been a dramatic decline in elective peptic ulcer surgery in Sweden that began long before the advent of fiberoptic endoscopy, highly selective vagotomy, or H2-receptor antagonists. The comparable decline in emergency procedures suggests that true changes in the incidence or severity of the disease have occurred. In the future the few patients still needing elective surgery for peptic ulcer may have to be served by a small number of specialized centers. PMID- 2589884 TI - Curative resection of multiple gastrinomas aided by selective arterial secretin injection test and intraoperative secretin test. AB - Recently a number of surgeons have recommended radical resection of gastrinomas in Zollinger-Ellison syndrome (ZES). We have developed a useful technique for preoperative localization of gastrinomas--the selective arterial secretin injection test (SASI)--and we recommend an intraoperative secretin test (IOS) for deciding the radicality of resection of gastrinomas. Here the results of SASI and IOS tests in 11 patients with ZES are examined and compared with the results of other techniques. The SASI test localized gastrinomas in all of the patients, while the sensitivity of ultrasonography, computed tomography, arteriography, or portal venous blood samplings was between 1/11 and 5/11. On the basis of the results of the SASI test, radical resection of gastrinoma was performed in four patients (three pancreatoduodenectomies and one extirpation). After pancreatoduodenectomy, immunohistologic study of the specimen revealed multiple microgastrinomas and lymph node metastases in two patients and the coexistence of a microgastrinoma and a gastinoma in one patient. The IOS test was useful in the estimation of the advisability of radicality, and in two patients total gastrectomy was not performed because of the results of the IOS test. These four patients are well and have returned to work, and their serum gastrin levels are below 35 pg/mL. Thus we believe SASI and IOS tests are helpful for planning curative resection of gastrinomas. PMID- 2589885 TI - Long-term injection sclerotherapy treatment for esophageal varices. A 10-year prospective evaluation. AB - Long-term injection sclerotherapy after proved variceal bleeding was assessed in 245 patients. The majority had alcoholic cirrhosis and the patients were equally distributed between modified Pugh-Child's risk grades A, B, and C. Esophageal varices were eradicated in 88% of the 140 patients who survived long enough for analysis, and remained eradicated for a mean of 19.4 months. The incidence of recurrent variceal bleeding after the first hospital admission was 0.02 bleeding episodes per patient month of follow-up study and was markedly reduced after eradication of varices. The overall cumulative survival rates at 1, 5, and 10 years were 54%, 39%, and 29%, respectively. The prognosis was influenced by the risk grade and the number of variceal bleeds before entering the study and to a lesser extent by the etiology of the cirrhosis. Fifty-two per cent of the patients died during the 10-year period. Liver failure was the major cause of death. Complications were mostly of a minor nature but they became cumulative with time. Minor complications included mucosal slough and injection-site leak, although the latter had an associated mortality risk. Significant esophageal stenosis and esophageal rupture were rare. As a result of this study a more radical surgical policy is proposed for sclerotherapy failures. These are defined as patients in whom varices are difficult to eradicate or who continue to have major variceal bleeds. Such patients should be subjected to either a portosystemic shunt or a devascularization and transection procedure. PMID- 2589886 TI - Early diagnosis of esophageal cancer. Analysis of 11 cases of esophageal mucosal cancer. AB - We reviewed 11 patients with esophageal mucosal carcinoma in various aspects to improve the early diagnosis of the disease. Eighteen lesions measuring 0.5 to 5.0 cm were confirmed histologically in the 11 cases. Histologically 10 of the 18 lesions were carcinomas in situ (ep cancer), and the other 8 lesions were carcinomas confined to the mucosa other than ep cancer (mm cancer); all 18 lesions were squamous cell carcinomas. Six (85.7%) of the seven mm cancers showed abnormal radiographic findings regardless of the size. Similarly these findings were noted on four of five (80%) ep carcinomas 2 cm or larger in size. All 15 lesions diagnosed before operation showed abnormal findings on conventional endoscopy regardless of the size and depth of transmural invasion. Morphologic change was observed in 9 lesions (53.3%), while 13 (86.7%) showed color change; most of the lesions (80%) were manifested as redness. Dyeing of the resected specimen with Lugol solution (Katayama Chemical Industries, Osaka, Japan) showed all 18 cancerous lesions as unstained areas. Among the 18 lesions, two lesions were unstained areas, which agreed with the areas determined histologically. An additional lesion was visible with dye endoscopy as an unstained area but it was not visible with radiography or conventional endoscopy. Dye endoscopy using Lugol solution is very important because it allows detection and evaluation of the extent of esophageal mucosal cancer. PMID- 2589887 TI - Neutrophil-dependent, oxygen-radical mediated lung injury associated with acute pancreatitis. AB - Cerulein-induced acute pancreatitis in rats is associated with a reversible lung injury that is characterized by alveolar capillary endothelial-cell injury, increased microvascular permeability, interstitial edema formation, and intraalveolar hemorrhage and fibrin deposition. The role of mediators in this injury was analyzed using gravimetric data, microvascular permeability indices, electron microscopy, and a quantitative morphometric analysis. Neutrophil depletion induced by a specific antibody was highly protective against lung injury. Interruption of the complement pathway (using low dose Naja naja cobra venom factor) also protected against lung injury. Catalase and superoxide dismutase were also protective. The iron chelator deferoxamine and the hydroxyl radical scavenger, dimethylsulfoxide, were not protective against acute lung injury. These data suggest that complement, neutrophils, and neutrophil-derived (H2O2-dependent) oxygen products mediate lung injury that occurs secondary to cerulein-induced pancreatitis. In contrast to other models of neutrophil dependent, oxygen-radical-mediated lung injury, this lung injury does not appear to be an iron-dependent and hydroxyl-radical mediated injury. We postulate that the process of acute pancreatitis leads to complement activation followed by neutrophil recruitment, sequestration, and adherence to alveolar capillary endothelial cells. Ultimately lung injury appears to result from local endothelial-cell injury secondary to neutrophil-generated oxygen products that may be myeloperoxidase dependent. PMID- 2589888 TI - Carcinoma of the gallbladder. The Roswell Park experience. AB - The median survival, from diagnosis, of patients with cancer of the gallbladder is 6 months. Our purpose in reviewing our experience was to identify factors, either in patient characteristics or treatment, that influence this statistic. In 22 years 71 cases of gallbladder carcinoma were referred to Roswell Park Memorial Institute in Buffalo, New York. Most had a cholecystectomy that revealed an unsuspected neoplasm, before referral. Mean age was 62 years and 75% were female. Symptoms, signs, and laboratory and imaging studies were uniformly unhelpful in determining the diagnosis. Early diagnosis at a stage amenable to surgical excision remains the sole salvation. Patients who receive chemotherapy did better than those who did not, but this is probably a reflection of patient selection. Newer treatment modalities are urgently needed. PMID- 2589889 TI - Chest injuries in childhood. AB - Differences in anatomy and mechanisms of injury are believed to contribute to the unique response of children to thoracic trauma. To characterize the scope and consequences of childhood chest injury, we reviewed the records of 105 children (ages 1 month to 17 years, mean 7.6 years) with chest injuries admitted to a level I pediatric trauma center from 1981 to 1988. Nearly all injuries (97.1%) were due to blunt trauma, and more than 50% were traffic related. Rib fractures, commonly multiple, and pulmonary contusions occurred with nearly equal frequency (49.5% and 53.3%, respectively), followed by pneumothorax (37.1%) and hemothorax (13.3%). One fourth of all pneumothoraces were under tension. Significant intrathoracic injuries occurred without rib fractures in 52% of cases with blunt trauma. Associated head, abdominal, and orthopedic injuries were present in 68.6% of children reviewed. One in five received endotracheal intubation and ventilatory support for 1 to 109 days. Presence or absence of head injury neither increased the need for respiratory support (29.4% vs. 17.2%, respectively; p = 0.24) nor affected the duration of support for those who were ventilated (6.8 +/- 8.9 days vs. 3.3 +/- 2.6 days, excluding one ventilator-dependent head-injured patient and five early deaths). The presence of associated injuries, intubation, and pneumothorax or hemothorax all resulted in significantly longer hospitalizations and more severe injury as measured by Injury Severity Score (ISS). Age, rib fracture, and contusion had no effect. Rarely encountered were ruptured diaphragm (2 cases), transection of the aorta (1), major tracheobronchial tears (3), flail chest (1), and cardiac contusion (2). Only two of the three children with penetrating injuries and three of the 83 (3.6%) with blunt injuries underwent chest operations. Six children (7%) died, one from a penetrating injury and five from blunt mechanisms. Chest Abbreviated Injury Scale (AIS) and ISS correlated significantly with mortality; age and head AIS did not. Rib fractures, lung contusions, and associated head, abdominal, and skeletal injuries are common because of the predominance of blunt-injury mechanisms. Nearly one half of chest injuries occurred without rib fractures. The need for ventilatory support is uncommon; when required, its duration is generally brief. Aortic transection, flail chest, and penetrating injuries more frequently encountered in adults and are uncommon in children. Thoracotomy generally is not required.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2589890 TI - Surgical significance of popliteal arterial variants. A unified angiographic classification. AB - Distal popliteal arterial variations may influence the success of femorodistal popliteal and tibial arterial reconstructions. Two patients whose bypass procedures were initially unsatisfactory because of a poor choice for anastomosis stimulated a review of variations in the distal popliteal artery in 1000 femoral arteriograms. The popliteal arterial anatomy could be assessed in 605 extremities and the tibial arterial anatomy in 495 extremities. Seventy-five variant cases were identified. Normal branching of the popliteal artery was present in 92.2%. Among the 7.8% incidence of variants, the majority (72%) were either high origin of the anterior tibial artery or a trifurcation pattern. Of variant patterns to the foot (5.6%), the most common was that in which the supply to the distal posterior tibial artery arose from the peroneal artery. We propose a unified classification of the popliteal and tibial arterial variations that encompasses both anatomic areas. Variant arterial supply to the foot can be suspected when the infrapopliteal vessels show a hypoplastic or aplastic anterior or posterior tibial artery and compensatory hypertrophy of the peroneal artery. Knowledge of these variants is important to angiographers and vascular surgeons. PMID- 2589891 TI - Late failure of reversed vein bypass grafts. AB - Late failure of reversed vein bypass grafts is preceded by the appearance of stenotic lesions, which progress to total occlusion. These lesions appear either as intrinsic graft lesions or as new arteriosclerotic lesions in contiguous arteries. The present study summarizes the University of Pennsylvania experience with these lesions in 521 vein grafts inserted from 1979 to 1985. The grafts were grouped according to the site of the distal anastomosis; 231 above-knee popliteal (FP AK), 171 below-knee popliteal (FP BK), and 119 tibial (FT). The overall incidence of stenotic lesions was essentially identical with the three grafts (21%), but the relative incidence of intrinsic graft to arterial lesions was higher with the more distal grafts. The most common graft lesions developed adjacent to the proximal anastomosis, which is the narrowest part of a reversed vein graft. The popliteal artery was the most common site of outflow stenosis. There was negligible incidence of tibial lesions. The most common inflow arterial lesion was located in the common femoral and iliac arteries. The superficial femoral artery (SFA) was a rare site of inflow stenosis, even though it was at risk because 96 grafts originated from the SFA or popliteal artery. Sixty-seven per cent of the graft and 52% of the arterial lesions were treated successfully by percutaneous transluminal angioplasty; the rest had minor surgical revisions. This resulted in a 19%, 10%, and 9% improvement in 5-year patency for the FT, FP BK, and FP AK bypasses. These results justify an aggressive policy of graft surveillance to identify and treat stenotic graft lesions before graft occlusion. PMID- 2589892 TI - Ultrasonic mucosal proctectomy in patients with ulcerative colitis. AB - A technique for performing mucosal proctectomy in patients with ulcerative colitis using ultrasonic fragmentation is described. Twenty-eight patients undergoing colectomy and ileoanal anastomosis were studied. Removal of the mucosal layer of the distal rectum was performed using a titanium probe vibrating at 23 kHZ with an amplitude of 300 microns. This method produces complete mucosal destruction and the resulting debris and irrigating fluid is removed through the hollow central portion of the probe. Healing of the ileoanal anastomosis does not appear to be adversely affected by the use of this technique. Because ultrasonic fragmentation is not dependent on the integrity of the submucosal plane, it may be advantageous in those cases in which severe inflammation and submucosal scarring make manual dissection of the rectal mucosa difficult to perform. PMID- 2589893 TI - Prognostic significance of DNA content abnormalities in young patients with colorectal cancer. AB - Several studies have shown that the presence of DNA ploidy abnormalities, measured by flow cytometry, may correlate with a poor prognosis in a variety of cancers. The predictive value of these DNA abnormalities in young patients with colorectal cancer has not been well studied. Fifty patients aged 40 years and younger with colorectal adenocarcinoma were studied to determine the correlation of tumor DNA abnormalities with survival. DNA content was determined by flow cytometric analysis and each tumor was categorized as diploid or nondiploid. Of the parameters studied, Dukes' classification and tumor DNA ploidy were found to be significant prognostic indicators. Determination of DNA content seems to provide additional useful prognostic information in young patients with colorectal cancer. PMID- 2589894 TI - [Effect of storage conditions on population variability and activity of Streptomyces recifensis var. lyticus]. AB - The results of the study on survival and variation of Streptomyces recifensis var. lyticus 2435 producing lytic enzymes are presented. The culture was maintained for 2.5 years under a layer of vaseline oil, at a temperature of -20 degrees C and in lyophilized state. It was shown that irrespective of the storage method strain 2435 preserved its viability. However, the most intensive growth was observed in the lyophilized cultures. During the storage the content of the productive colonies characteristic of the morphological type culture in the population decreased while the number of the low active variants increased. Lyophilization of the strain spores in the sucrose-gelatine medium provided insignificant morphological variation of the culture and preservation of the initial level of its lytic activity against a number of test-microbes except S. aureus and M. lysodeikticus. Storage of the culture under vaseline oil and at a temperature of -20 degrees C resulted in lowering of its lytic activity against all the test-microbes used. For long-term maintenance of Streptomyces recifensis var. lyticus 2435 the method of lyophilization in the sucrose-gelatine medium is recommended. PMID- 2589895 TI - [A spectrophotometric method of analysis of fusidic acid]. AB - A spectrophotometric method for assay of fusidic acid is described. The method is based on reaction with a reagent consisting of acetic anhydride and concentrated sulfuric acid. Mathematical processing of the results of the main substance determination in fusidic acid preparations showed that the error did not exceed 2 per cent. Procedures for spectrophotometric assay of fusidic acid in control of the processes of its biosynthesis, isolation and purification were developed. The procedures provided control of the technological process of fusidic acid production. PMID- 2589896 TI - [Production of toxic shock exotoxin by Staphylococcus aureus strains resistant and sensitive to antibiotics]. AB - Three hundred and ninety two strains of S. aureus isolated from bacteria carriers and patients with staphylococcal infections in different regions of the Soviet Union were investigated. 55.9 per cent of the isolates were able to produce exotoxin of toxic shock. No regular relation between resistance to definite antibiotics (tetracycline, chloramphenicol, benzylpenicillin, streptomycin, lincomycin, erythromycin, oleandomycin, gentamicin and methicillin) and the polyresistance range on the one hand and the ability to produce toxic shock exotoxin on the other hand was revealed. PMID- 2589897 TI - [Immunostimulating effects of muramyl dipeptide, glucosaminyl muramyl dipeptide and their synthetic derivatives in vitro]. AB - The effect of muramyldipeptide (MDP), glucosaminylmuramyldipeptide (GMDP) and their six synthetic derivatives on production of tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-2 (IL-2) by murine spleen cells in vitro was studied. MDP induced insignificant TNF production and did not stimulate production of IL-1 by the murine splenocytes within a 24-hour cultivation period whereas in combination with lipopolysaccharide (LPS) it induced significant production of both the cytokins. GMDP induced marked production of TNF (54 per cent cytotoxic index) and IL-1 (stimulation index 8). Addition of LPS in an amount of 10 ng/ml increased production of TNF by the murine splenocytes under the effect of GMDP but had no effect on production of IL-1. Neither MDP nor GMDP even in combination with LPS induced production of IL-2 by splenocytes of mice DVA/2 and C57B1/6 at activation for 24 hours. All the synthetic derivatives of MDP and GMDP except the MDP polymer activated TNF production by the murine spleen cells. GMDP lysine had the highest effect: 67 per cent cytotoxic index. In combination with LPS its cytotoxic index amounted to 87 per cent. The TNF activity was always higher when LPS in an amount of 10 ng/ml was added to the glycopeptides. PMID- 2589898 TI - [Effect of the antineoplastic antibiotic bruneomycin on lymphocyte population ratio in mice]. AB - Data on the quantitative ratio of the populations of T- and B-cells in the lymphoid organs of mice at various periods after oral administration of bruneomycin are presented. It was shown that in contrast to the total number of T and B-cells in the spleen and mesenteric lymph nodes amounting to the minimal values at the early periods (days 1-3) after the antibiotic injection, their relative content remained rather high. Complete recovery of the number of T- and B-lymphocytes in the above organs was observed only by the end of a month period. Study on the kinetics of the immune response to sheep red blood cells showed that reactivity of the antibody producers in the experiments with bruneomycin increased 1.5-2 fold as compared to the control. PMID- 2589900 TI - [Gnotobiotic studies to determine the colonization resistance of the intestines]. AB - The literature data and the results of the author studies on determination of intestine colonization resistance are presented. The mechanisms of the colonization resistance defined by the macroorganism factors and representatives of indigenic microflora are discussed. The results of the experiments with animal gnotobiotes aimed at elucidating new aspects of the colonization resistance mechanism: antagonistic interrelations between pathogenic and nonpathogenic bacteria and the role of transitory microflora, factors lowering the colonization resistance are presented. The up-to-date methods for testing the colonization resistance and the ways for its increasing are indicated. PMID- 2589899 TI - [Effect of sisomicin on intestinal microflora and colonization resistance in rats and their offspring]. AB - In experiments with Wistar female rats it was shown that after administration in the form of inhalations (10.87 mg/m3) sisomicin was present in the animal feces in a concentration of 26.6 micrograms/g. Prolonged exposure to the antibiotic during the pregnancy term led to changes in microbiocenosis of the animal large intestine which was observed even a month after the delivery. The progeny of the animals was characterized by the presence of significant numbers of aerobic bacteria resistant to sisomicin and potentially pathogenic gram-negative bacteria including various species of Proteus in the intestine, as well as by higher periods of persistence of Klebsiella indicator strains administered orally. PMID- 2589901 TI - [Effect of carbohydrates on possible utilization of wastes from antibiotic manufacturing plants in the construction industry]. AB - Utilization of antibiotic manufacture waste containing a certain amount of carbohydrates in concrete preparation requires their control. It was shown that the content of not more than 0.5 per cent of carbohydrates in the waste had no unfavourable effect on the concrete hardening. PMID- 2589902 TI - [Phagocytosis of chloramine B sensitive and resistant staphylococci isolated from healthy persons and patients]. AB - Phagocytic reaction with respect to antibiotic and chloramine B sensitive and resistant staphylococci isolated from healthy persons and patients, air and stock of medical institutions was studied on albino mice. It was shown that the staphylococcal isolates included strains simultaneously sensitive to antibiotics and chloramine, sensitive to antibiotics and resistant to chloramine, resistant to antibiotics and sensitive to chloramine and simultaneously resistant to antibiotics and chloramine. Activity, intensity and completeness of phagocytosis by leucocytes from mouse abdominal cavity exudates with respect to the staphylococcal strains sensitive to antibiotics and resistant to chloramine, resistant to antibiotics and sensitive to chloramine and simultaneously resistant to antibiotics and chloramine were lower than the values of the phagocytic reaction with respect to the isolates simultaneously sensitive to antibiotics and chloramine. This suggested that not only antibiotic resistance of microbes but also their resistance to disinfectants could be referred to complicating factors of hospital infections. PMID- 2589903 TI - [Pharmacokinetic monitoring of antibiotic therapy]. AB - The general strategy in optimization of antibiotic dosage regimens included development of population or common regimens for an "average" patient (the 1st approximation), subpopulation regimens for patients of certain categories on the basis of interactions between the pharmacokinetic parameters and "patient factors" (the 2nd approximation) and individual regimens on the basis of the data of the pharmacokinetic monitoring (the 3rd approximation). Characteristics of every of the approximations in antibiotic therapy of adults and children were analyzed. Out of the peculiarities of the strategy use in pediatrics+ and micropediatrics+ the following should be indicated: (1) pharmacokinetic heterogeneity of the population requiring grouping of the patients and consequently development of subpopulation dosage regimens omitting stage I, (2) possible development of dosage regimens on the basis of the ration between the pharmacokinetic parameters or immediate drug concentration values and the "patient factors" not only in chronic but also in transitory impairment of some functions and (3) the necessity of considering systematic changes in "pharmacokinetic status" of every child during individualization of the dosage regimens by the data of the pharmacokinetic monitoring. PMID- 2589904 TI - [Pharmacokinetics of azlocillin in critical conditions: an individualized schedule of drug administration in relation to anatomo-physiologic and pathologic factors]. AB - Azlocillin pharmacokinetics was studied after a single intravenous injection of the antibiotic in a dose of 4 g in 20 patients in critical state. To elucidate the causes of significant individual variability of the antibiotic pharmacokinetics observed in the patients, multiple correlation analysis of the main pharmacokinetic parameters i. e. the area under the concentration/time curve, total clearance, steady-state volume of distribution and mean residence time was performed in regard to the "patient factors" such as sex, age, the volumes of transfused liquid, blood, plasma and blood substitutes, hemoglobin levels, erythrocyte count and ESR. Adequate correspondence of the predicted by the "patient factor" values of the areas under the concentration/time curve and the total clearance to the actually determined values was observed. Correspondence of the predicted values to the steady-state volume of distribution and the mean residence time to the actually determined values was satisfactory. A procedure for design of azlocillin individual dosage regimens based on calculating individual clearance by the "patient factors" is described. PMID- 2589905 TI - Turnover time of Leydig cells and other interstitial cells in testes of adult rats. AB - The aim of this study was to investigate the turnover of Leydig cells and other interstitial cells in the adult rat testis. Normal adult rats received injections of [3H]thymidine at 9:00 and 21:00 for 2, 5, or 8 days. The percentage of labeled Leydig cells, which was initially low (0.8% +/- 0.2%), gradually increased during treatment to 1.4% +/- 0.3%. The percentage of labeled peritubular cells was considerably higher and increased from 1.4% +/- 0.1% to 3.5% +/- 0.4% during [3H]thymidine treatment. The remaining interstitial cells were the most actively proliferating cells: the percentage of labeled cells increased from 2.4% +/- 0.2% to 7.5% +/- 0.8% during [3H]thymidine treatment. Leydig cells, peritubular cells, and the remaining interstitial cells in the adult rat testis undergo proliferation. By means of a linear regression analysis and an arcsin transformation, an estimation of the time interval needed to replace various types of interstitial cells was obtained. Taking into account the 95% confidence interval, the turnover time of Leydig cells ranged from 142 to 2823 days. The calculated turnover time for the peritubular cells was 85 to 257 days. PMID- 2589906 TI - Human follicular fluid adverses hamster spermatozoa motility. AB - To determine the optimal conditions for in vitro spermatozoa vitality, human and hamster spermatozoa were incubated at 37 degrees C in T6 medium supplemented with different biologic fluids (10% v/v). The fluids tested were human serum (HUS), hamster serum (HAS), and human follicular fluid (HUF). After incubation the spermatozoa were investigated for their qualitative and quantitative motility. Human spermatozoa maintained a good vitality in all fluids tested (approximately 25% motility after 18-h incubation). The hamster spermatozoa had after an incubation of 4 h a motility of 28.4% in HUS, 14.2% in HAS, and 2.2% in HUF. The quality of the motility was also extremely low in HUF, whereas it was adequate in HUS and in HAS. The presence of species-specific substances in mammalian follicular fluid is discussed. PMID- 2589907 TI - Critical assessment of sperm morphology before and after double wash swim-up preparation for in vitro fertilization. AB - Critical assessment of sperm morphology using specific and stringent criteria is predictive of the subsequent ability of those sperm to fertilize oocytes in in vitro fertilization (IVF). Previous studies have evaluated sperm morphology prior to sperm preparation and, thus, have not assessed the actual sperm used for insemination. We studied the impact of a double wash swim-up technique used for IVF on sperm morphology using the strict criteria of Kruger et al. [5, 6] in 73 consecutive patients undergoing IVF. Pre- and postswim-up morphological assessments were done in a prospective, randomized, and blinded fashion. The mean percentage of normal forms pre- and postswim-up was 19.8% and 23.4%, respectively, an improvement of 18% (p less than 0.05) with 62 of 73 patients showing improvement. Significantly, analysis of the 27 patients with abnormal morphology on initial assessment (normal forms less than or equal to 14%) revealed an improvement in percentage of normal forms from 9.0% to 21.5%, a mean increase of 239% (p less than 0.005). Eighteen of these 27 patients showed improvement in their percentage of normal forms, eight were unchanged, and only one patient had a decline in their percentage of normal forms. We conclude that the double wash swim-up preparation used for IVF substantially improves the percentage of sperm with normal morphology, and that the benefit is most substantial in those cases where the percentage of normal morphology is abnormal. PMID- 2589908 TI - Hypoosmotic swelling test in the prediction of male fertility. AB - The hypoosmotic swelling test (HOS) is a simple test to measure the functional competence of human sperm membranes. The question is, does a relationship exist between this competence and the fertilization potential of human spermatozoa? In this study the strongest correlation (r = 0.76) was obtained between sperm swelling and sperm viability (supravital staining). Only a moderate correlation (r = 0.50) was obtained with normal sperm morphology; weaker correlations were also obtained with the sperm penetration assay (r = 0.42) and human IVF (r = 0.24). The results, therefore, indicate that the HOS test has a limited predictive value. Notwithstanding this low concordance between sperm swelling and fertilizing potential, a less than 50% HOS test threshold was seen to be a definite indicator of a male factor. PMID- 2589909 TI - Zinc binding to major human seminal coagulum proteins. AB - In vitro binding of zinc to proteins of the human ejaculate and of the various male accessory gland secretions was evaluated. The proteins were separated by sodium dodecyl sulfate gel electrophoresis and transferred to nitrocellulose filters that were subsequently incubated with 65ZnCl2. High levels of zinc binding were observed to approximately 20 protein bands (14 to 70 kDa) of the coagulated seminal plasma. There was only low binding to proteins of the spermatozoa and virtually no binding to any protein of the epididymal and prostatic fluids. When sperm liquefaction was allowed to occur, 65ZnCl2 binding to high-molecular weight proteins decreased rapidly, and after 15 min only the binding to proteins of molecular weights less than 25 kDa remained. In addition, zinc concentration was determined both in the centrifugate and in the supernatant after centrifugation of the coagulum. Zinc concentrations in the centrifugate and the supernatant were, respectively, 147 +/- 72 micrograms/g and 31 +/- 22 micrograms/g. The whole supernatant contained only 12% +/- 4% of total sperm zinc. Finally, in highly viscous sperm samples the concentration of zinc was not significantly different from that in normally liquefying sperm (167 +/- 87 micrograms/ml compared to 188 +/- 107 micrograms/ml). The main extracellular targets of prostatic zinc in humans are the secreted seminal vesicle proteins. The role of this binding remains unknown, however, because no direct relationship could be established between the concentrations of this metal and the phenomena of coagulation and liquefaction. PMID- 2589910 TI - Calcium uptake in human spermatozoa: characterization and mechanisms. AB - Basal 45Ca2+ influx was analyzed in human seminal spermatozoa using a method that allows these highly reactive cells to be easily and safely handled. The uptake was a time-dependent process, with its maximum at 400 s. The kinetics of 45Ca2+ transport was saturating as a function of extracellular Ca2+ concentration with a Km of 429 microM and a Vmax of 1.6 nmol 45Ca2+/mg protein/2.5 min. Depolarizing conditions and the calcium channel blocker verapamil did not affect the uptake; based on this, the presence of operating calcium channels in seminal spermatozoa is excluded. The independence of 45Ca2+ uptake on external concentration of both Na+ and Ca2+ suggests that Na+/Ca2+ exchange does not occur in these cells. The anticalmodulin drug trifluoperazine, the mitochondrial inhibitor antimycin A, and the SH reagents N-ethylmaleimide and mersalyl all inhibited the ion transport. A calmodulin-regulated, energy-requiring, proteinaceous Ca2+ transporter seems to be the main operating mechanism of calcium uptake in human seminal gametes. PMID- 2589911 TI - Zinc uptake in human seminal spermatozoa: characterization and effects on cell membranes. AB - Human ejaculated spermatozoa take up zinc in a time- and concentration-dependent manner. The kinetics of 65Zn2+ uptake is suggestive of an at least partly carrier mediated transport. The lack of effect of the respiratory chain inhibitor antimycin A could mean that mitochondrial ATP is not required as an energy source for the uptake. The failure of nonpermeant SH reagent mersalyl to modify zinc uptake indicates that functional membrane sulfhydryl groups are not involved in the process. A dose-dependent inhibition of 65Zn2+ uptake was induced by the "anticalmodulin" drug trifluoperazine, suggesting that the calcium-binding protein calmodulin could have a role in zinc transport. In in vitro experiments this cation brought about a powerful effect in protecting the spermatozoa from being damaged by hypo-osmosis. PMID- 2589912 TI - Exaggerated orthostatic hypotension as first sign of diabetic autonomic neuropathy in the elderly. AB - Long-standing diabetic subjects have an impaired sympathetic nervous system activity as a consequence of autonomic neuropathy. Moreover, in this latter group of subjects the parasympathetic rather than the sympathetic nervous system seems firstly impaired by glucose metabolism derangements. In the present study we show that, in aged diabetic subjects with a short duration of the disease (less than 5 years), and who are free from diabetic complications, it is possible to evidence a primary compromise of sympathetic rather than parasympathetic nervous system activity since a greater rate of orthostatic hypotension occurred. In the light of the well-known age-related changes in the physiopathology of cardiovascular activity, we hypothesize that in aged diabetic patients, even after a short duration of disease, sympathetic compromise precedes the derangement of parasympathetic nervous system activity. PMID- 2589913 TI - Measurement of renal functions by double isotope techniques in elderly patients during tenoxicam therapy. AB - Four elderly patients (aged 68-87 yr) with osteoarthritis were treated with 20 mg of tenoxicam (a new non-steroidal anti-inflammatory drug) daily for at least 12 weeks. Tenoxicam did not appear to have any harmful effect on glomerular filtration rate and effective renal plasma flow, as measured by a single intravenous injection of 51Cr-EDTA and 125I-iodohippurate. Plasma concentration of tenoxicam indicated good compliance, and no evidence of unexpected accumulation of tenoxicam in the plasma was observed during 12 weeks of medication. PMID- 2589914 TI - Knowledge about aging and perception of the old by Nigerian nurses. AB - Interviews of 168 Nigerian nurses were made to determine their knowledge about aging, their perceptions of old people and their opinions regarding geriatric medicine in Nigeria. Data analyses reveal that nurses have positive perceptions of old people, appear knowledgeable about medical aspects of aging and not so knowledgeable about mental health problems of the old. Constraints to geriatric practice were seen in the personal characteristics of the old, the youth-oriented medical set-up and the socio-cultural values which discourage the old from seeking care. Discussions focus on the implications of the findings for health care delivery to the old. PMID- 2589915 TI - Reduced lipofuscin accumulation in senescent rat brain by long-term acetyl-L carnitine treatment. AB - By using fluorescence microscopy and microfluorimetric techniques, the effects of ageing and of 11 months acetyl-L-carnitine (ALCAR) treatment on lipofuscin deposition within the cytoplasm of pyramidal neurons of rat prefrontal cortex and hippocampus (CA3 field) were assessed. No lipofuscin autofluorescence was observed in the nerve cell bodies of neurons under study in young rats (3 months of age), but lipopigment had accumulated in the same nerve cells of senescent rats (22 months of age). ALCAR administration significantly reduced the accumulation of lipofuscin within pyramidal neurons of the brain areas examined. PMID- 2589916 TI - Blood pressure and functional aspects of the aging brain. AB - This study was carried out to define the effects of both long-term hypertension and hypotension on the cerebral functioning of the elderly, comparing them to the effects of normotension. Ninety-eight subjects of both sexes, between 70 and 82 years of age, were divided into three groups on the basis of their mean blood pressure: 33 normotensives, 36 hypotensives and 29 hypertensives. They underwent a neuropsychological assessment, a haemorrheological evaluation and an EEG monitoring while awake. The results show that the three parameters were almost always within normal limits in the normotensives, while EEG alterations, lower neurophysiological scores and blood hyperviscosity were noted in both the hypertensives and hypotensives. Our results would seem to confirm that long-term hypertension may induce alterations in the cerebral electrogenesis and intellectual functions of the elderly and that also long-term hypotension might negatively interfere with some functional aspects of the aging brain. PMID- 2589917 TI - Pathophysiology of the immune system in elderly subjects with or without diabetes and variations after recombinant interleukin-2. AB - This study reports two groups of elderly diabetic patients and normal subjects, with or without hypercholesterolemia and hypertriglyceridemia, who presented a decrease of the T lymphocyte-mediated function, proliferative capacity, phagocytosis, cytotoxicity and surface markers. This fall was more evident in hypercholesterolemic and hypertriglyceridemic subjects. The humoral responses and other parameters studied did not reveal significant variations. The authors also observed that recombinant interleukin-2 (rIL-2) stimulation determined a satisfactory response in healthy and diabetic subjects, while it did not normalize values in patients with altered lipid balance. PMID- 2589918 TI - Elimination of the delayed postischemic energy deficit in cerebral cortex and hippocampus of aged rats with a dried, deproteinized blood extract (Actovegin). AB - In this study, the effect of Actovegin (AC) on glucose and energy metabolism of cerebral cortex and hippocampus after 15 minute complete cerebral ischemic (cci) and postischemic recirculation periods of 60 min, 24 h, 48 h, 72 and 96 h was investigated. The study was performed on 2-year-old male Wistar rats which may be designated as aged. Actovegin is a dried, deproteinized extract of calf blood which acts on mitochondrial respiration and energy metabolism. After cci, the metabolic abnormalities measured as concentrations of glucose, lactate, creatine phosphate (CrP), and adenosine triphosphate (ATP) normalized rapidly. After 48 h and 72 h postischemic recirculation, however, an imbalance in energy metabolism became manifest in cerebral cortex, and even earlier (24 h), longer (96 h), and more severely in hippocampus. AC (1 ml diluted with 1 ml distilled water/day; 1 ml AC contains 40 mg dried deproteinized extract) counterbalanced the postischemic abnormalities in cerebral cortex and hippocampus. This drug may be able to reduce the detrimental effects to the neuron during postischemic recirculation and may thus help the neuron to survive during this critical period. PMID- 2589919 TI - Mortality of demented patients in a geriatric institution. AB - A group of 237 elderly patients with dementia of Alzheimer type (DAT) or multi infarct dementia (MID) was randomly selected in a large geriatric institution in Milan. Mean age of the sample was 78.9 years, 160 (67.5%) were DAT patients and 77 (32.5%) were MID patients. Half of the sample had low levels of autonomy and after 4 years 183 (77.2%) patients were dead. Predictors of mortality, according to a univariate analysis, were age, level of autonomy and type of diagnosis (DAT vs. MID). Mortality rate after 4 years was significantly higher (p less than 0.001) in DAT (86.9%) than in MID (57.1%) patients. PMID- 2589920 TI - Lipoprotein profiles and their relation to animal fat intake in healthy old people from four Spanish localities. AB - In studies carried out on 401 individuals from different Spanish regions, blood lipoprotein levels do not show a clear relationship to amounts of animal fat intake because diet habits change in old age. But in these persons there was a significant and positive correlation between actual LDL levels and animal fat intake when they were 40-45 years old. Similar results are obtained with HDL, but correlations are inversely proportional. Our study leads to the interpretation that diet habits during the first phase of the adult life span are determinant for the lipoprotein profiles in older ages, which can still be observed in very old individuals. PMID- 2589921 TI - Anaerobic degradation of aniline and dihydroxybenzenes by newly isolated sulfate reducing bacteria and description of Desulfobacterium anilini. AB - A new, rod-shaped, Gram-negative, non-sporing sulfate reducer (strain Ani1) was enriched and isolated from marine sediment with aniline as sole electron donor and carbon source. The strain degraded aniline completely to CO2 and NH3 with stoichiometric reduction of sulfate to sulfide. Strain Ani1 also degraded aminobenzoates and further aromatic and aliphatic compounds. The strain grew in sulfide-reduced mineral medium supplemented only with vitamin B12 and thiamine. Cells contained cytochromes, carbon monoxide dehydrogenase, and sulfite reductase P582, but no desulfoviridin. Strain Ani1 is described as a new species of the genus Desulfobacterium D. anilini. Marine enrichments with the three dihydroxybenzene isomers led to three different strains of sulfate-reducing bacteria; each of them could grow only with the isomer used for enrichment. Two strains isolated with catechol (strain Cat2) or resorcinol (strain Re10) were studied in detail. Both strains oxidized their substrates completely to CO2, and contained cytochromes, carbon monoxide dehydrogenase, and sulfite reductase P 582. Desulfoviridin was not present. Whereas the rod-shaped catechol oxidizer (strain Cat2) was able to grow on 18 aromatic compounds and several aliphatic substrates, the coccoid resorcinol-degrading bacterium (strain Re10) utilized only resorcinol, 2,4-dihydroxybenzoate and 1,3-cyclohexanedion. These strains could not be affiliated with existing species of sulfate-reducing bacteria. A further coccoid sulfate-reducing bacterium (strain Hy5) was isolated with hydroquinone and identified as a subspecies of Desulfococcus multivorans. Most probable-number enumerations with catechol, phenol, and resorcinol showed relatively large numbers (10(4)-10(6) per ml) of aryl compound-degrading sulfate reducers in marine sediment samples. PMID- 2589922 TI - Hyperactive boys almost grown up. IV. Criminality and its relationship to psychiatric status. AB - Attention-deficit disorder with hyperactivity is believed, by some, to be a developmental antecedent (predisposing factor) to antisocial personality disorder and criminality. However, evidence supporting this association has not been consistent. We report on a prospective follow-up study of 103 males (ages 16 to 23 years), who were diagnosed as hyperactive (attention-deficit disorder with hyperactivity) between ages 6 and 12 years, and 100 normal controls. The official arrest records of all subjects who resided in New York State during the follow-up interval were obtained. Blind diagnoses (based on structured interviews with subjects and their parents) were made on 98% of the initial cohort at follow-up. Although other investigators have reported on the delinquent behavior of hyperactive children in a prospective design, to our knowledge, follow-up mental status has not been studied previously in relation to official arrest records. Significantly more probands than controls had been arrested (39% vs 20%), convicted (28% vs 11%), and incarcerated (9% vs 1%). The presence of an antisocial/conduct disorder in young adulthood almost completely accounted for the increased risk for criminal activities in the former hyperactive children whether or not it was accompanied by a substance use disorder. Continuing attention-deficit disorder with hyperactivity at follow-up, by itself, was not associated with arrest history. The findings support the view that childhood attention-deficit disorder with hyperactivity is a risk factor for later criminality, but that this relationship is almost exclusively mediated by the development of an antisocial disorder in early adulthood. PMID- 2589923 TI - Reliability of anxiety assessment. I. Diagnostic agreement. AB - Test-retest reliability of lifetime anxiety disorder diagnoses was determined using the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety version. The subjects were 104 patients at an anxiety research clinic. Reliability ranged from good to excellent (kappa = +.60 to +.90) for generalized anxiety, social phobic, panic, agoraphobic, and obsessive-compulsive disorders. Simple phobia showed poor agreement. Current episodes showed better agreement than past episodes, particularly for social phobia and obsessive-compulsive disorder. Major sources of disagreement (variance in subject report, rate error, criterion ambiguity) were reviewed for each diagnosis and implications for DSM-IV are proposed. PMID- 2589924 TI - Reliability of anxiety assessment. II. Symptom agreement. AB - Accurate assessment of "subdisorder" anxiety symptoms, ie, anxiety symptoms central to DSM-III-R-diagnosed anxiety disorders but not meeting disorder criteria because of insufficient frequency, duration, or accompanying subjective distress or impairment, may be critical to case identification in genetic, epidemiologic, and high-risk studies. However, concerns that the mild and often transient nature of these phenomena will foster unreliability have discouraged their use. We assessed the test-retest reliability of "subdisorder" anxiety symptoms in 104 outpatients with anxiety. Good to excellent agreement was found for lifetime occurrence of any panic attack, the spontaneous and situationally predisposed subtypes of panic, and five nonsocial irrational fears (public transportation, driving oneself, crowds, situations associated with death [eg, dead bodies and funerals], and cats and dogs). Four social and three additional nonsocial fears were considered to have adequate reliability. However, agreement on stimulus-bound panic, "near" panic attacks, persistent generalized anxiety, and the remaining nine nonsocial and six social irrational fears was only fair to poor. The major source of unreliability was variation in information reported by the subject to the rater. PMID- 2589925 TI - Somatic manifestations in women with generalized anxiety disorder. Psychophysiological responses to psychological stress. AB - Generalized anxiety disorder is associated with symptoms that suggest heightened muscular tension and autonomic arousal. Since self-reports of physiological states in patients with anxiety disorder are frequently unreliable, we compared 20 female patients with generalized anxiety disorder with a matched group of nonanxious controls on a battery of psychophysiological assessments (skin conductance, heart interbeat interval, blood pressure, respiration, and forehead and gastrocnemius electromyographic activity). We found that during baseline patients with generalized anxiety disorder differed from controls on electromyographic, but not on autonomic, measures. During psychological stress tasks, patients with generalized anxiety disorder showed a weaker mean skin conductance response with a narrower range in both skin conductance and heart rate than controls. These findings suggest that sympathetic inhibition, rather than enhancement, occurs in patients with generalized anxiety disorder during performance stress. PMID- 2589926 TI - Electrodermal activity in young adults at genetic risk for affective disorder. AB - Low electrodermal activity has been proposed as a trait marker for affective disorder. We attempted to determine if low electrodermal activity could be a genetic marker by testing subjects at genetic risk for affective disorder. High risk subjects, 22 offspring of a parent with bipolar affective disorder, and 27 low-risk controls 15 to 25 years old had skin conductance recorded bilaterally during rest periods, presentation of 10 nonsignal tones, and performance of reaction-time and mental arithmetic tasks. There were no significant differences in skin conductance levels under any condition or in the frequency or amplitude of orienting responses to nonsignal tones. During task periods high-risk subjects showed significantly greater electrodermal activity that was lateralized to the left hand. Self-rated depression was higher in the high-risk group during task periods. The results show that low electrodermal activity is not a likely genetic marker for affective disorder but suggest that autonomic hyperresponsivity, atypically lateralized information processing, and depressive affect occur during mild stress in persons at risk for the development of affective disorder. PMID- 2589927 TI - Wilson's disease. Psychiatric symptoms in 195 cases. AB - A series of 195 cases of Wilson's disease were assessed retrospectively on a range of variables, including psychiatric, neurologic, and hepatic symptoms, and biochemical data as recorded at first admission to a specialist clinic. Ninety nine patients (51%) were rated as displaying some evidence of psychopathologic features, and 39 (20%) had seen a psychiatrist before the diagnosis of Wilson's disease. The most common psychiatric features were abnormal behavior and personality change, although depression and cognitive impairment were also rated frequently. Schizophrenialike psychoses were rare, apparently occurring at no more than chance frequency. Psychiatric symptoms were related to neurologic rather than hepatic symptoms, and certain symptoms (incongruous behavior, irritability, and personality change) had a particularly significant relationship with bulbar and dystonic disorders but not with tremor. Psychiatric manifestations are important in Wilson's disease, and many of the psychopathologic features seem to have an organic basis. PMID- 2589928 TI - Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease. AB - Schizophrenia is associated with structural changes (eg, a mild degree of ventricular enlargement) in the brain, although whether these precede onset of illness or progress with episodes is not established. In a postmortem study, we find that ventricular enlargement affects the posterior and particularly the temporal horn of the lateral cerebral ventricle. By comparison with controls and with patients suffering from Alzheimer-type dementia (in which there is also temporal horn enlargement), the change is highly significantly selective to the left hemisphere. This deviation was not accompanied by an increase in glial cell number (examined chemically by assay of diazepam-binding inhibitor immunoreactivity and microscopically by density of staining with the Holzer technique). The findings are consistent with the view that schizophrenia is a disorder of the genetic mechanisms that control the development of cerebral asymmetry. PMID- 2589929 TI - The pendulum swings the other way: the role of environment obscured by genes. PMID- 2589931 TI - [Pharmacokinetic studies of the activity of a pH-labile alpha-L arabinofuranosidase following i.v. injection into tumor-bearing mice]. AB - In order to increase the selectivity of tumor chemotherapy, Graffi et al. have proposed the application of xenogenic enzymes, which are able to split transport forms of carcinostatics under the pH-conditions in the tumor more vigorously than in the normal tissues. This paper describes the distribution within the body and elimination of the activity of the pH-labile alpha-L-arabinofuranosidase from G. myabena compared with the pH-stable enzyme from A. niger, using tumor bearing mice. In vitro, the pH labile arabinosidase was irreversibly inactivated within a few minutes at pH 7.4 and 37 degrees C; however at pH 6.5 it remained active even after several hours. After injection, this enzyme activity was eliminated from the organism by excretion and inactivation within a few hours. Hereby a relatively favourable distribution of the enzyme activity for therapeutic application was reached after 60 minutes. At this time higher activity than in the tumor was measured only in the kidney. The application of glucose led to a strong increase of the enzyme activity in both tumor and normal tissues. This effect was also seen in tumor free mice. In further experiments it will be tried to find out conditions which reduce the glucose induced acidosis. The activity and distribution of the pH-stabile enzyme from A. niger were not influenced by glucose application. PMID- 2589930 TI - Molecular, biochemical and morphological aspects of the dynamics of rat stomach mucous membrane changes in experimental carcinogenesis induced by N-methyl-N' nitro-N-nitrosoguanidine (MNNG). AB - The dependence of gastrocarcinogenesis on biochemical and morphological disorders of the stomach mucous membrane, i.e. epimolecular alteration of chromatin structure, inhibition of pepsinogen synthesis, alteration of ontogenetic heritage of glandular epithelium was studied in 450 random-bred white rats with the aid of a model of gastrocarcinogenesis induced with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). This agent weakened the DNA-protein linkage in the chromatin. The irreversibility of this phenomenon coincided with the crucial point of the MNNG gastrocarcinogenesis (precancer sign appearance). The consequences of MNNG induced specific alteration of epithelial stem cells became inherited (stomach adenocarcinoma development). In parallel with gastrocarcinogenesis, concomitant deficiency of pepsinogen-pepsin in the mucous membrane also developed. The data suggest that deficiency of the enzyme was in some degree obliged to alteration of pepsinogen mRNA synthesis. PMID- 2589932 TI - Experimental induction of embryo-derived teratomas and teratocarcinomas in mice. AB - The present study deals with the induction of teratomas and teratocarcinomas in two strains of mice (C3H/Bln and 129/terSv). 6 to 7 days old egg cylinders were transplanted beneath the kidney capsule of adult syngeneic male and female recipients. Out of 115 grafted embryos 32 gave rise to teratoid tumors. Both the overall tumor incidence (teratomas and teratocarcinomas) and the overall percentage of teratocarcinomas were approximately the same in the strains used. In strain C3H/Bln the gender of the recipient seemed to influence the outgrowth of malignant tumors. Two transplantable C3H-teratocarcinomas could be established (DTC-4, DTC-8). Up to date both have retained their pluripotent differentiation pattern which makes them useful for intended further investigations. PMID- 2589933 TI - [Therapeutic results and toxic side effects of the combination cytostasan, adriamycin and vincristine as second-line therapy of metastatic breast cancer]. AB - Remission rate of 30-50% can be obtained by different cytostatic combinations in second-line-therapy of the metastasized breast cancer. The combination of adriamycin and vincristine with cytostasan reveals a remission rate of 52% in 50 CMF-pretreated female patients. Considerable toxic side effects led to a dose reduction of cytostasan and adriamycin in 31 female patients without clinical efficiency loss. The long remission periods of the total responders (5+ -23 months) are remarkable. Both 3 female patients with bone +/- soft tissue metastasis and 3 female patients with visceral metastasis benefited from a clinical total remission. The remission rates indicated no significant differences between the group of patients with soft tissue +/- bone metastasis (56.3%) and that with a predominantly visceral metastasis (50.0%). The CyAV combination with a low dose provides an effective therapeutical scheme with acceptable side effects for CMF-pretreated female patients with breast cancer. PMID- 2589934 TI - [The necessity for a stratification of patients with radically resected rectal cancer]. AB - In contrast to the increasing incidence of rectal tumours the treatment results have reached a plateau. For their improvement it is necessary to exhaust all treatment modalities currently available. One approach might be centralized therapy at specialized hospitals (to use capacities and abilities located there) and another approach is the use of adjuvant treatments in certain patients. To secure optimal results of adjuvant treatments the patients should be stratified for some acknowledged prognostic factors. PMID- 2589935 TI - Cytophotometric and interference microscopic investigations in carcinomas of the oral cavity. AB - The DNA content and the nuclear dry mass of 18 keratinized squamous cell carcinomas and their metastases, of one adamantinoma recurrence and two adenoid cystic carcinomas of the oral cavity were determined in comparison to the normal buccal mucosa using Feulgen scanning cytophotometry and interference microscopy. The squamous cell carcinomas could be classified into five groups based on their DNA distribution pattern. The nuclear dry mass and its variation were found to be different from the normal mucosal epithelial cells in all cases. No differences could be found between diploid cells and cells of a higher degree of ploidy. Therefore the relation of nuclear dry mass and DNA content appeared to be lower in cells of higher DNA ploidy. This fact is discussed in relation to the underlying molecular biological processes. This leads to the conclusion that the increase of the nuclear dry mass (mainly protein) precedes the increase of the DNA content. The combined measurement of DNA content and nuclear dry mass allows a better characterization of malignancy than each of the nuclear components measured alone. The difference of nuclear dry mass between malignant cells and normal mucosal epithelial cells is more sensitive than the deviation of the DNA content owing to the fact that malignant tumours with normal DNA content exist. PMID- 2589936 TI - [Methods of standardizing relative survival rates using rectal cancer in East Germany as an example]. AB - Statistical analyses concerning survival of cancer patients are mostly based on the concept of relative survival rates, which besides the crude survival rates, calculated by the life-table-method, take into account the influence of other (competing) causes of death. But the use of relative survival rates by no means a full reduction of the influence of age. Methods for standardization of such rates will be presented and demonstrated on the data of the National Cancer Registry in GDR for rectum cancer in 1980. PMID- 2589937 TI - Organization of cancer care in Austria. PMID- 2589938 TI - Organization of cancer care in Hungary. PMID- 2589939 TI - [Temperature, pH value, acid load and filterability of normal human erythrocytes: in vitro studies, possible significance for hyperthermic tumor therapy. Comments on the paper by W.K. Barnikol]. PMID- 2589940 TI - Diverse immunoreactivity and metachronous ultrastructural variability in fatal primitive childhood tumor with rhabdoid features. PMID- 2589941 TI - The pathogenesis of atherosclerosis in aortocoronary saphenous vein grafts. PMID- 2589942 TI - Factor VIII-related antigen in the cardiac myxoma: its relevance to tumor histogenesis. PMID- 2589943 TI - Organ-specific variation in the morphology of the gungomas (fungus balls) of Pseudallescheria boydii. PMID- 2589944 TI - Evolving concepts of quality in laboratory practice. A historical overview of quality assurance in clinical laboratories. AB - Early concepts of quality in clinical laboratory services stressed accuracy and precision. In the 1960s voluntary and mandated programs for laboratory accreditation followed. The increasing complexity of laboratory standard setting led to the promulgation of voluntary consensus standards in the 1970s. This was followed by a national reference system to minimize bias among clinical laboratories. The concept of total quality control emphasized that quality assurance must be a way of life for laboratorians, and concerns about growing laboratory volume led to the idea that managing laboratory utilization is also a component of quality assurance. Recent conferences have expanded the concept of laboratory quality to encompass everyone who participates, even remotely, in the provision of services. Now quality is evaluated by how well the patient is served. PMID- 2589945 TI - Some characteristics of the community practice of pathology in the United States. National Manpower Survey of 1987. AB - An evaluation of 629 pathologists engaged in community hospital and private laboratory practice and representing 601 pathology practices of varying size shows surprising uniformity in the distribution of professional effort. On average, pathologists in community practice distribute their effort as follows: surgical pathology, 34.6%; autopsy pathology, 6.7%; cytology, 8.8%; clinical pathology, 18.0%; teaching, 6.0%; research and development, 2.3%; laboratory administration, 17.5%; hospital administration, 2.9%; and other, 3.2%. The average community pathologist is male, 52 years of age, and a graduate of an American medical school (60%). When surveyed in 1986, community pathologists worked an average of 50 hours per week and retired at an average age of 62 years. PMID- 2589946 TI - The impact of fine-needle aspiration biopsy on a diagnostic electron microscopy laboratory. AB - We retrospectively reviewed the number and types of diagnostic electron microscopic specimens from a 4 1/2-year period. During this period, the number of fine-needle aspirate biopsy specimens processed increased in a linear fashion, from a relatively uncommon occurrence to the current level of activity, in which fine-needle aspiration specimens now represent 40% to 50% of the nonrenal diagnostic material examined by electron microscopy. This study documents the increasing importance of fine-needle aspirate-type specimens in the everyday operation of a diagnostic electron microscopy facility. PMID- 2589947 TI - Calcium oxalate crystals in breast biopsies. An overlooked form of microcalcification associated with benign breast disease. AB - Two distinct forms of microcalcification are found in breast disease. The more commonly recognized type is basophilic and nonbirefringent and consists predominantly of calcium phosphates (type II). The other type is a birefringent, colorless crystal that is composed of calcium oxalate (type I). It has not been emphasized in the literature that calcium oxalate can produce radiopacities and yet is easily overlooked in tissue sections. In this study, histologic sections taken from 127 randomly selected, mammographically directed biopsies were reviewed and the presence or absence of microcalcifications, the type of microcalcification, and the associated disease process were noted in each case. Seventy-eight of the 127 specimens were obtained because of suspicious calcifications detected by mammography and 9 (11.5%) contained only type I microcalifications, 9 (11.5%) contained both types I and II microcalcifications, and 48 (61.5%) contained only type II microcalcifications; in 12 specimens (15.4%), microcalcifications were not identified. The overall incidence of type I calcifications was 17.3% (22/127), but the incidence in those specimens obtained because of calcifications detected by mammography was 23.1% (18/78). Type I microcalcifications were found only in benign cysts and were not associated with carcinoma or epithelial hyperplasia, whereas type II microcalcifications were associated with benign or malignant lesions. These findings are in keeping with the hypothesis that type I microcalcifications are a product of secretion whereas type II microcalcifications are a result of cellular degeneration or necrosis. In biopsies in which type II microcalcifications are not identified, examination of sections under polarized light may reveal the presence of calcium oxalate crystals. PMID- 2589948 TI - A hospital-wide blind control program for bedside glucose meters. AB - We have instituted hospital-wide proficiency testing of nursing personnel who operate glucose-monitoring instruments. Whole blood samples with known glucose levels were distributed to all nursing units for analysis on a biweekly basis. Measurements obtained by nurses on glucose meters were compared with one another and with true glucose levels to identify discrepant performance and institute corrective action. After 10 months of operation, we found that the nursing units using glucose meters daily showed mean absolute variation from true glucose of 12.7% (range, 10.0% to 17.7%), whereas intermittent users showed mean absolute variation of 15.3% (range, 10.7% to 24.0%). Of 552 total paired determinations, 199 (36.9%) differed from true glucose by greater than 15%. This program was successful in establishing uniform quality control procedures among nonlaboratory personnel who had no previous experience in laboratory measurements. PMID- 2589949 TI - A case of disseminated Phialophora parasitica infection. AB - The numbers and kinds of fungi that are known to cause human mycoses have increased greatly in the past decade. We report the first case (to our knowledge) of disseminated Phialophora parasitica infection. The patient, a 92-year-old woman, had known chronic subcutaneous infection with P parasitica. The systemic nature of her disease was diagnosed at autopsy, when the organism was identified in cultures obtained from a thrombus within an abdominal aortic aneurysm and was also histologically demonstrated within sections obtained from the aneurysm wall. PMID- 2589950 TI - Intrahepatic biliary cysts in congenital biliary atresia. AB - A case of pronounced cystic dilatation of the intrahepatic bile ducts with biliary atresia is presented. Intrahepatic biliary cysts have been described in biliary atresia, although, as far as we are aware, none as extensive as in this case. The cysts represent end-stage obstruction with irreversible liver injury; thus, drainage of these cysts does not alleviate the condition. The differential diagnosis includes Caroli's disease, congenital hepatic fibrosis, and polycystic liver disease. PMID- 2589951 TI - Osmotic stress, osmotic myelinolysis, and oligodendrocyte topography. AB - Hyponatremia and rapid correction of hyponatremia have often been proposed as pathogenetic mechanisms in the development of central pontine myelinolysis. We report the case of a 36-year-old man who died with acute hemorrhagic pancreatitis with the autopsy findings of central pontine and extrapontine myelinolysis. The patient had developed moderate serum hyperosmolality during the first 3 days of his illness, and it persisted until his death 20 days later. Hyponatremia or rapid correction of hyponatremia never occurred. These observations suggest that osmotic stress and oligodendrocyte topography rather than rapid correction of hyponatremia may be the key to the development of central pontine myelinolysis (osmotic myelinolysis). PMID- 2589952 TI - Necrobiotic xanthogranuloma with paraproteinemia. AB - Necrobiotic xanthogranuloma with paraproteinemia is a distinct clinicopathologic entity defined by skin lesions that are characteristic both clinically and histologically, as well as a by variety of hematologic and chemical abnormalities. It is frequently associated with multiple myeloma or chronic lymphocytic leukemia. A patient with the characteristic findings but with an unusual course is described. PMID- 2589953 TI - 'Polyposis vaginalis' of pregnancy. AB - Clinical and pathologic findings in a pregnant 15-year-old with vaginal polyposis disclosed numerous polyps throughout the vagina and portio of the cervix that disappeared spontaneously 6 weeks post partum. These polyps can be confused microscopically with sarcoma botryoides, although they are benign and may regress completely. PMID- 2589954 TI - Hamartoma of the urachal remnant. AB - A case of urachal hamartoma occurred in the urinary bladder of a 45-year-old woman, whose presenting symptoms were frequent urination and nocturia. Computed tomographic and contrast radiologic examinations demonstrated a broad-based 5-cm polypoid mass at the dome of the bladder. Grossly the polypoid mass was smooth surfaced and covered by innocent transitional epithelium. The mass and the underlying bladder wall consisted of multiple cystic cavities of various sizes and hyperplastic smooth-muscle bundles. Light microscopy identified numerous tubuloglandular structures, most of them lined by transitional cell epithelium. Simple or ciliated columnar cells and occasional mucous cells were also present, particularly in the epithelium of cystic cavities. Some tubules had communicated with the bladder lumen. Hamartoma of the urachal remnant should be included in the differential diagnosis of urachal and bladder tumors. PMID- 2589955 TI - Diabetes insipidus caused by lymphocytic infundibuloneurohypophysitis. AB - Pathologic examination at autopsy of a 74-year-old man with central diabetes insipidus revealed that he had a chronic lymphocytic inflammation limited to the infundibulum, stalk, and posterior lobe of the pituitary gland. No meningitis, sarcoidosis, or granulomas were detected, though there was evidence of chronic pancreatitis. In addition, neuronal loss with gliosis was observed bilaterally in the supraoptic and paraventricular nuclei. The unusual localized inflammatory brain lesion was considered to be responsible for the diabetes insipidus. PMID- 2589957 TI - Anti-antivivisection. Have we waited too long? PMID- 2589956 TI - Diffuse fatal pulmonary microembolism of retroperitoneal extravascular origin. AB - A 34-year-old woman who had type I diabetes mellitus for 22 years and chronic renal failure for 2 years underwent a combined kidney and pancreas transplantation. Her uremia and insulin-dependence disappeared thereafter. However, she suddenly developed acute respiratory distress and died 22 days after the surgery. Diffuse pulmonary microemboli composed of necrotic tissue debris, fat cells, and muscle fragments were found. The source of the emboli was apparently a localized liquefying hematoma with necrotic muscle and fat in the left retroperitoneal space. Although such an occurrence seems to be extremely rare, the present case demonstrates that a liquefying hematoma with necrotic tissue in a confined space may indeed give rise to fatal pulmonary microembolism. PMID- 2589958 TI - Ongoing 'threats' to biliary surgery. PMID- 2589959 TI - Cosmesis and local control after irradiation in women treated conservatively for breast cancer. AB - One hundred twenty-two patients (124 tumor sites) with breast carcinoma (T1 to T3, N0 to N2, M0) were treated by a lumpectomy and radiation therapy at the University of Wisconsin, Madison, from June 1978 to December 1986. Irradiation to the breast and regional lymph nodes was carried out with cobalt 60 teletherapy in 2-Gy fractions to 50 Gy, followed by an additional boost of 10 Gy to the tumorectomy site with coned electrons. Cosmesis was analyzed by scoring the effects of surgery, as well as the effects of irradiation, and by photographic assessment. After a follow-up of 24 to 119 months (median, 36 months), 82% of the patients were found to have good or excellent cosmetic scores. There was a trend that favored better cosmetic results in younger patients and in patients with outer-quadrant lesions. No significant impact of adjuvant chemotherapy on the cosmetic outcome or on the complications of treatment was demonstrated. There were six local recurrences (5.2%), three of which were true recurrences and the other three that were new primary tumors; 11 distant failures (9%) occurred. The following side effects from irradiation developed in only 5 patients (4.1%): match-line fibrosis (n = 2), soft-tissue necrosis (n = 1), and persistent tenderness (n = 2). The conditions of the two patients with persistent tenderness responded favorably with conservative management. We concluded that a lumpectomy, followed by radiation therapy, provides good cosmetic results without compromising the local control rate. If adjuvant chemotherapy is planned, we recommend that it be administered before radiation therapy in favor of concomitant therapy with both modalities. PMID- 2589960 TI - Current results of treatment for distant metastatic well-differentiated thyroid carcinoma. AB - Between 1960 and 1986, 37 patients were treated at M. D. Anderson Hospital and Tumor Institute, Houston, Tex, for metastases beyond the thyrocervical region arising from well-differentiated thyroid carcinomas. Patient, tumor, and treatment factors were analyzed in this group for their influence on survival. No specific factors achieved statistical significance; however, patients having more than one site of metastasis and patients whose metastases arose less than 5 years after treatment of the primary tumor tended to have shorter overall survival times. More than one modality of treatment was used in the majority of patients. Complete surgical resection of metastases offered the best chance for prolonged survival and palliation. With long survival times being the rule, several treatment modalities are often required to provide continuous palliation. PMID- 2589961 TI - Oxygen delivery in patients with adult respiratory distress syndrome who undergo surgery. Correlation with multiple-system organ failure. AB - Identification of the physiologic determinants of survival in patients with adult respiratory distress syndrome (ARDS) has been largely unsuccessful. We evaluated multiple physiologic variables over the first three reversible phases of ARDS. A stepwise multivariant linear regression analysis was used to identify correctable physiologic correlates with survival. Our goal was improved survival. We found that the oxygen delivery and alveolar-arterial oxygen gradient on the third day after the diagnosis of ARDS were the two most important correctable correlates. Both eventually effected the development of multiple-system organ failure and survival. These data provide clinical evidence that optimization of both the oxygen delivery and alveolar-arterial oxygen gradient after the onset of ARDS may allow resolution of ARDS, prevent additional organ dysfunction, and improve survival. PMID- 2589962 TI - The incidence of decreased red blood cell deformability in sepsis and the association with oxygen free radical damage and multiple-system organ failure. AB - We studied the incidence of decreased red blood cell deformability (RBCD) in sepsis and the association between decreased RBCD and oxygen free radical generation (as measured by malonyldialdehyde) and the occurrence of multiple system organ failure (MSOF). Patients were divided into three groups: septic (n = 28), nonseptic (n = 15), and control (n = 5). Serial measurements of deformability index, malonyldialdehyde, and MSOF were made. The deformability index for the septic group (0.23 +/- 0.17) was significantly less than that for the nonseptic (1.12 +/- 0.48) and control (1.11 +/- 0.25) groups. The malonyldialdehyde levels for the septic group (4.5 +/- 1.0 nmol/mL) were significantly greater than those for the nonseptic (2.7 +/- 0.9 nmol/mL) and control (2.6 +/- 0.8 nmol/mL) groups. The MSOF index for the septic group (10.1 +/- 2.5) was significantly greater than that for the nonseptic (7.6 +/- 1.7) and control (6.0 +/- 0.0) groups. An inverse correlation existed between malonyldialdehyde and deformability index ( = .501, less than .001, n = 40) and between deformability index and MSOF index (= .350, less than .05, n = 61). We conclude that RBCD is decreased during human sepsis; free radicals generated during sepsis may play a role in the decrease in RBCD. Decreased RBCD may contribute to the MSOF that occurs during sepsis. PMID- 2589963 TI - Development of a bacteria-independent model of the multiple organ failure syndrome. AB - Criteria that allow definition of the multiple organ failure syndrome include pulmonary, hepatic, renal, and gut barrier dysfunction along with characteristic histopathologic changes. It has been difficult to study multiple organ failure due to lack of a satisfactory experimental model that would reproduce the pathophysiologic and histopathologic characteristics, would be stable enough to allow study over several days, and would be free of exogenous primary bacterial infection. We have studied pathophysiologic and histopathologic alterations in a potential model of multiple organ failure. Wistar rats received one of the following solutions by intraperitoneal injection: 4 mL of saline, 4 mL of mineral oil, or 1 mg per gram of body weight of zymosan A in 4 mL of mineral oil. Animals that received zymosan developed hypoxia, decreased creatinine clearance, and changes in hepatic microsomal cytochrome P450 content and aniline hydroxylase activity. Bacterial translocation occurred in the zymosan group. The lungs, liver, and kidneys of the animals that received zymosan exhibited histopathologic changes. We conclude that this model fulfills our criteria for a model of multiple organ failure. PMID- 2589964 TI - Tumor necrosis factor induces adult respiratory distress syndrome in rats. AB - To evaluate the effect of tumor necrosis factor (TNF), a major mediator of sepsis, on lung structure and function, we infused 200-g male Wistar rats with TNF (0, 2 x 10(5), or 4 x 10(5) U/kg of TNF) for 24 hours. Volume-pressure measurements were determined in the excised lungs using both air and saline, which eliminated surface tension forces. Total lung wet and dry weight, nitrogen level, and DNA and protein content were measured. Lungs of the rats that received TNF accepted significantly smaller volumes of air and saline at all pressures compared with the control group. Both the lung wet and dry weights increased with TNF. Lung DNA and protein content also increased, suggesting increased cellularity in the TNF-infused lungs. Thus, the lungs of the TNF-treated rats were stiffer, with reduced compliance values, and heavier due to increased water content and increased cellularity. These data indicate that sublethal administration of TNF in this rat model induces the adult respiratory distress syndrome and increases the work potential of respiration. PMID- 2589965 TI - Enhanced effectiveness of intraperitoneal antibiotics administered via liposomal carrier. AB - The local application of antibiotics to treat intraperitoneal contamination has been used with variable results. Liposomes are not rapidly absorbed from the peritoneal cavity, offering a potential delivery system for intraperitoneal antibiotics. The effects of liposome-incorporated antibiotic administration in a fecal peritonitis model were compared with the effects of conventional intraperitoneal and intramuscular antibiotics. Rats were divided into four groups: untreated, intramuscular cefoxitin, intraperitoneal cefoxitin, and intraperitoneal liposome-incorporated cefoxitin. Quantitative blood cultures were drawn at 4 and 24 hours. Liposome delivery of cefoxitin significantly reduced mortality and bacteremia at 4 and 24 hours compared with control subjects and conventional antibiotic groups. Peritoneal abscess formation tended to decrease in the liposome antibiotic group (mean +/- SEM, 6.86 +/- 0.79) compared with the group receiving free intraperitoneal administration of antibiotics (10.33 +/- 1.63). We conclude that liposomal delivery significantly enhances the effectiveness of cefoxitin in this model of peritonitis. PMID- 2589966 TI - Kupffer cell cytotoxicity to hepatocytes in coculture requires L-arginine. AB - Activated macrophages convert L-arginine to citrulline and unstable nitrogen oxides that have cytotoxic properties. We recently have shown that the inhibition of protein synthesis in Kupffer cell (KC):hepatocyte (HC) coculture, following exposure to gram-negative bacterial endotoxin (lipopolysaccharide), is due to the metabolism of L-arginine by this cytotoxic pathway. Although this finding supports a role for activated KCs and the L-arginine-dependent mechanism in the HC dysfunction seen in sepsis, it and previous studies have failed to demonstrate direct damage to HCs by adjacent KCs. The current study was undertaken to determine if KCs exposed to lipopolysaccharide could directly damage HCs and, if so, whether the damage was dependent on the metabolism of L-arginine. By using the release of aspartate aminotransferase as a marker of HC damage, it was found that a significant aspartate aminotransferase release by KC:HC cocultures in response to lipopolysaccharide occurred only if L-arginine was present. In addition, requirements for significant aspartate aminotransferase release included KC:HC ratios of 7.5:1 or greater and L-arginine concentrations of 1 mmol or more. Although the KC-induced damage was mild, these results show that in vitro HC damage in KC:HC coculture does require the metabolism of L-arginine and supports a hypothesis that toxic L-arginine metabolites may contribute to liver cell damage in patients with sepsis. PMID- 2589967 TI - Endotoxin tolerance is associated with reduced secretion of tumor necrosis factor. AB - Bacterial endotoxin effects are partially mediated by tumor necrosis factor (TNF). It is known that sublethal doses of endotoxin induce transient refractoriness (tolerance) to some of its effects. We studied the role of TNF in endotoxin tolerance in rats. Weight loss, lethality, and TNF production were measured after an initial dose of endotoxin and after subsequent doses. Weight loss reached its peak 72 hours after the initial endotoxin challenge, followed by recovery even under continued administration of endotoxin. While tolerant, rats could survive a dose of endotoxin that was lethal for 100% of naive rats. The high serum levels of TNF, observed 90 minutes after the first dose of endotoxin, markedly diminished when rechallenged during tolerance. Recovery of responsiveness to these effects followed the refractory phase by 3 weeks. We concluded that endotoxin tolerance is associated with a reduced secretion of TNF. PMID- 2589969 TI - Agenesis of the gallbladder. PMID- 2589968 TI - What's in a name? Is methicillin-resistant Staphylococcus aureus just another S aureus when treated with vancomycin? AB - Methicillin-resistant Staphylococcus aureus (MRSA) strains, principally resistant to penicillinase-resistant penicillins and aminoglycosides, are increasingly common hospital isolates. We have examined the significance of MRSA colonization and infection in 1100 consecutively admitted, seriously burned patients in whom vancomycin was used to treat all staphylococcal infections. Colonization with S aureus (SA) was identified in 658 patients, in 319 of whom MRSA colonization was identified. Two hundred fifty-three SA infections occurred in 178 patients; of these infections, 58% were pulmonic and 38% were bacteremic. Methicillin resistant SA infections occurred in 58 of the SA-infected patients. A severity index, based on multiple-regression analysis of mortality as a function of burn size and age in the study population, was used to estimate expected mortality. We demonstrated no measurable increase in mortality attributable to MRSA in this population of burned, SA-infected patients. The results question the clinical and economic value of added control practices, such as closing of units, refusal of transfer or admission, added isolation, treatment of carriers, furlough of colonized staff, and other expensive measures that are specifically directed at prevention of MRSA infections in critical care areas. PMID- 2589970 TI - [In vitro detection of ovalbumin-specific IgA producing cells from lymphocytes of patients with hen-egg allergy]. AB - We studied antigen-specific IgA production from the peripheral lymphocytes of children with hen-egg allergy by using the method of indirect plaque forming cell (PFC) assay. The number of OVA-specific IgA-PFC generated from the patient lymphocytes was low (6 +/- 3/7 X 10(4) non T cells) in comparison with age matched normal children (112 +/- 18/7 X 10(4) non T cells). The numbers of OVA specific IgG-PFC and IgM-PFC generated from the patient lymphocytes were not so different from those of the age-matched normal children. This indicates that the activity of OVA-specific IgA-antibody production was reduced in patients with hen egg allergy. PMID- 2589971 TI - [Immunochemical quantification of the airborne mite allergens]. AB - We collected airborne particle from indoor air by using a high-volume air sampler, and measured mite allergens in the air-filter extract by use of RAST inhibition assay. The results obtained were as follows: 1) The assay revealed the presence of house dust mite allergen in the indoor air varying from 690 to 129000 pg/m3. 2) In apartments, seasonal fluctuations of house dust mite allergen in the indoor air demonstrated a peak in autumn (September and October), and showed a tendency to increase in spring. In our outpatient clinic, the quantity of house dust mite allergen in the indoor air varied from 690 to 5670 pg/m3, while there were few mites on the floor, and showed a tendency to increase in winter. 3) There was a significant correlation between the quantity of house dust mite allergen in the indoor air and the number of mite in house dust (r = 0.535, p less than 0.01). 4) The amount of D.f. allergen in the indoor air was significantly decreased by using air cleaners (p less than 0.005). These results showed that the quantification of house dust mite allergen was useful from the clinical point of view as a parameter of mite pollution indoors, and it was important for asthmatics to live in clean environment, and to decrease the number of mites in house dust. PMID- 2589972 TI - [Allergen tests with midge allergens in Moriyama City, located on the south coast of Lake Biwa]. AB - The main species of midge which emerge from the Lake Biwa, the biggest lake in Japan, are Tokunagayusurika akamusi (TA) and Chironomus pulmons. In order to determine how the existence of Lake Biwa affects the positivity to allergen tests with midge allergens, randomly selected asthmatic patients were examined by skin test and RAST. Out of 129 patients, 35 (27%) were positive to scratch tests with an extract of Chironomus yoshimatsui (CY). Out of 64 patients, 16 (25%) were positive to TA RAST and 12 (19%) were positive to CY RAST. The positive rate of skin tests was highest in the patients aged between 20 and 39. The positive rate of TA RAST was not significantly higher than the rates reported in other districts of Japan. PMID- 2589973 TI - [Comparison of a new specific IgE assay Quidel allergy screen to skin prick test, intradermal test, and RAST]. AB - Quidel Allergy Screen (QAS), an enzyme-linked immunosorbent assay, has been developed for measuring IgE antibodies against 9 allergens (HD 1, HD 2, Mite 1, Mite 2, Japanese cedar, ragweed, cat dander, sweet vernal grass, and egg white) at the same time. To determine whether this assay is useful in screening allergen specific IgE antibody, we compared the titers of IgE antibodies against the 9 allergens measured by QAS to the obtained in skin prick tests, in intradermal tests and by RAST in 93 atopic asthmatics and 25 normal subjects. We found a good agreement between the reactivity of skin prick tests and the reactivity of QAS. There was a significant correlation between the threshold doses of intradermal tests and the titers of QAS. We also found a good agreement between the reactivity of RAST and the reactivity of QAS, and a strong correlation between the titers of RAST and the titers of QAS. Thus, it is concluded that QAS is useful in screening IgE antibodies against multiple allergens simultaneously. PMID- 2589974 TI - [Cellular immunoregulation in atopic dermatitis--hyperresponsiveness to interleukin-4 and hyporesponsiveness to interleukin-2]. AB - We examined the responsiveness to Interleukin-4 (IL-4) and Interleukin-2 (IL-2) of peripheral blood lymphocytes from patients with atopic dermatitis (AD) and non AD controls. The IL-4 responsiveness of the AD patients was found to be higher than that of the non-AD controls. In contrast, the IL-2 responsiveness of the AD patients was relatively lower than that of the non-AD controls. When IL-4/IL-2 responsiveness ratio was compared, the IL-4/IL-2 responsiveness ratio of the AD patients (54.1 +/- 18.5) was significantly higher than that of the non-AD controls (24.8 +/- 9.9, p less than 0.001). The high IL-4/IL-2 responsiveness ratio found in the AD patients may possibly be related to the pathogenesis of AD. PMID- 2589975 TI - [Clinical research of specific IgE and IgG4 antibody in allergic children. Examination by multiple factor analysis-type II. (objective variables: specific IgE antibodies and IgG4 antibodies to food allergen)]. AB - We examined the influence power of 16 explanation variables to specific IgE antibody and IgG4 antibody to egg white cow's milk, and soybean in 150 asthmatic children by Multiple Factor Analysis-Type II 16 examination variables; 1) sex, 2) age, 3) onset age, 4) IgE RIST, 5) eosinophile count, 6) IgE RAST score to house dust, 7) IgE RAST score to Dermatophagoids farinae, 8) atopic dermatitis, 9) allergic rhinitis, 10) family history of allergy, 11) positive counts of food allergen: IgG4, 12) specific IgG4 antibody to cow's milk, 13) specific IgG4 antibody to soybean, 14) exercise induced asthma, 15) severity of asthma. The following results were obtained. 1) To introduce range relative ratio, we were able to use all 16 explanation variables on the occation of calculating by Multiple Factor Analysis-Type II. 2) 4 explanation variables (specific IgG4 antibody to soybean, IgE RIST, IgE RAST score to Dermatophgoides farinae, age) had the stronger influence power to 8 objective variables than the other explanation variables. 3) Only 2 explanation variables (specific IgE antibody to soybean, family history of allergy) had the stronger influence power to 8 objective variables than the other explanation variables. PMID- 2589976 TI - [Hourly variations in the dispersion of Japanese cedar (Cryptomeria japonica) pollens in the Yamagata basin and the effect of cold and warm fronts on the pollen counts]. AB - Airborne pollen counts of Cryptomeria japonica (CJ) were investigated at three points in the Yamagata Basin: 1. the central part of Yamagata City (point A), 2. at the foot of a mountain with a CJ grove (point B), 3. within the CJ grove (point C). At the beginning of the CJ pollen season, the airborne pollen counts at point B showed higher values than those at point A, whereas the relation of the count values was reversed later at the major pollen dispersion period. Numerous airborne pollens were detected at point C during the daytime, but few at night. On the other hand, many airborne pollens were found at point A during both the day and night. These results suggest that the pollens which come to rest on the roofs of houses and the pavement surfaces may be blown up into the air again. It was found that many pollens could be counted before a warm front passed through point A but that few pollens could be counted at the passage of a cold front. PMID- 2589977 TI - [Study on the clinical usefulness of RAST using insect and mite allergen discs]. AB - In order to examine the usefulness of mite and insect RAST, RAST was carried out on 79 asthmatic patients using mite, cockroach, mosquito and larval chironomid midge (Chironomus thummi thummi, CTT) allergen discs supplied from Pharmacia AB, and discs of two species of adult chironomid midge (Tokunagayusurika akamusi, TA and Chironomus yoshimatsui, CY in Japan) which were prepared in our laboratories. The results were as follows. 1) The positive rate of RAST in 65 randomly selected asthmatic patients was 62% in the case of mite, 25% for TA, 20% for CY, 14% for cockroach, 11% for CTT, 8% for silk and 6% for mosquito. The positive rates of silk and mosquito RAST were low. However, these RAST seemed to be clinically useful when patients were positive to these RAST. 2) The rate of coincidence between skin test and RAST was 86.5% in the case of mite and 30% in the case of silk. The rate of coincidence between prick test using adult CY and RAST using larval CTT was 46.5%. 3) The positive rate of larval CTT RAST was about half that of adult TA or adult CY. However, larval CTT RAST seemed clinically useful when patients were positive to the RAST, because all the patients who were positive to larval CTT RAST were also positive to both adult TA and CY RAST. 4) A significant correlation was found among the three kind of chironomid midge RAST and also between cockroach RAST and any of the three kinds of chironomid midge RASTs. PMID- 2589978 TI - [Influence of theophylline and corticosteroid preparations on serum PAF acetylhydrolase activity in asthmatic children]. AB - In our previous papers, we reported that serum PAF acetylhydrolase (PAF AH) activity in severely asthmatic children was lower than that in healthy or mildly asthmatic children, and that this enzymatic activity might be one of the factors that induce more severe respiratory symptoms in asthmatic children. In this study, we investigated the influence on PAF AH activity of theophylline and corticosteroid preparations, which are frequently used for the treatment of patients with bronchial asthma. Serum PAF AH activity and theophylline concentration were measured before and 3,4,6, 12 h after administration of a sustained-release theophylline preparation to 8 asthmatic children. Although the theophylline concentration was increased significantly at 3, 4 and 6 h after administration, PAF AH activity was unchanged, and there was no correlation between the two parameters. We then measured PAF AH activity in 6 asthmatic children before and 5 and 48 h after intravenous injection of 100 mg hydrocortisone succinate, and found no change in enzymatic activity. Furthermore, PAF AH activity in two severely asthmatic patients, who were being given low-dose corticosteroid on alternate days, was measured at regular intervals for 10 months in one case and 5 months in the other. The PAF AH activity showed no significant change in this period. These results show that PAF AH in asthmatic children is very stable, and is not affected by either theophylline or corticosteroid preparations. PMID- 2589979 TI - Effects of human recombinant interleukin 5 and 3 on the differentiation of cord blood-derived eosinophils and basophils. AB - When mononuclear cells from umbilical-cord blood were cultured for 3 weeks, low concentrations of interleukin 3 supported the preferential growth of basophils, with eosinophils comprising a smaller proportion. These basophils contained 0.15 0.3 microgram histamine per 10(6) cells, and released histamine by the IgE dependent and -independent stimuli. Interleukin 5 increased the number and proportion of eosinophils in a dose-dependent manner without affecting the proliferation of other cell types in the interleukin 3-supplemented cultures. These cultured eosinophils could be activated by platelet-activating factor. PMID- 2589980 TI - [Dermatophagoides farinae and Japanese cedar (sugi) pollen specific immunoglobuline E antibodies in asthmatic children measured by radioallergosorbent test and enzyme-linked immunosorbent assay]. AB - In recent years, pollinosis caused by Japanese cedar pollen (Cryptomeria japonica, sugi in Japanese) has been increasing strikingly in Japan. To investigate the prevalence and age-related sensitization of sugi pollen in children, the specific IgE antibody was determined in 204 asthmatics (129 boys, 75 girls) by the enzyme-linked immunosorbent assay (ELISA) and radioallergosorbent test (RAST), and compared to Dermatophagoides farinae (D.f.). There was a good correlation in the total serum IgE levels measured by ELISA and PRIST. We think that the ELISA is a reliable and valuable method which uses no radioactive material in a massive epidemiological survey. D.f. specific antibody levels increased in early infancy and remained high, and there was no difference between ELISA and RAST score. The sugi-basic-protein specific antibody measured by ELISA was detected in early infancy, and increased slowly for 5 to 6 years reaching its highest level at 7 to 12 years followed by decreasing levels, as revealed by both ELISA and RAST. Infants born in spring, the sugi pollinating season, showed a lower level of sugi-specific IgE because they were exposed the pollen 6 months to one year later. We believe that sensitization of Dermatophagoides farinae in early infancy could influence subsequent sensitization by sugi pollen in later life. PMID- 2589981 TI - [Clinical research of specific IgE and IgG4 antibody in allergic children. Correlation specific IgE antibody to specific IgG4 antibody to food allergen]. AB - We analysed the correlation specific IgE antibodies to specific IgG4 antibodies to food allergens in 150 asthmatic children by Multiple Factor Analysis-Type II and examined the role of both antibodies. The following results were obtained. 1) Of soybean, there was the stronger influence power between specific IgE and IgG4 antibody than the other 2 food allergens. 2) IgE antibody to soybean had the strong influence power to IgG4 antibodies to egg white and cow's milk and IgG4 antibody to soybean had same influence power to IgE antibodies to egg white and cow's milk. So, the specific IgE and IgG4 antibodies to soybean may be play the role of "the bride" between specific IgE antibody group and specific IgG4 antibody group of food allergens. PMID- 2589982 TI - Anti-allergic action of glucocorticoids (II). Effect of glucocorticoids on cell mediated (type IV) allergic reactions. AB - The effects of three glucocorticoids (steroids; hydrocortisone, prednisolone and dexamethasone) on cell mediated hypersensitivity (type IV) reactions in rats and mice were studied. All the steroids inhibited both the induction and the effector phases of type IV reaction induced by sheep red blood cells (SRBC) in mouse footpads. The local graft vs host reaction induced by lymphocytes from Brown Norway rats into the footpads of (Lewis x Brown Norway) F1 rats was also clearly inhibited by steroids. The inhibitory action of steroids on footpad reactions induced by SRBC was clearly prevented by pretreatment with non-corticoidal steroids (17 alpha-methyltestosterone, androstenedione and progesterone). The release of lymphokines, macrophage chemotactic factor (MCF) and skin reactive factor (SRF) was inhibited by each steroid at a high concentration. Moreover, steroids inhibited the activity of MCF in vitro and SRF in vivo. PMID- 2589983 TI - T lymphocyte subsets in the peripheral blood in patients with primary biliary cirrhosis. AB - T lymphocyte subsets and natural killer (NK) cells in the peripheral blood of 10 patients with primary biliary cirrhosis (PBC) were examined by using various kinds of monoclonal antibodies directed to the surface markers of the lymphocytes. We found that the population of Leu 2a+, Leu 15- cytotoxic T cells was decreased in PBC patients compared to normal controls, especially in those with a high serum titer of anti-mitochondria antibodies. However, there was no significant difference in the population of Leu 2a+, Leu 15+ suppressor T cells between PBC patients and normal controls. Although the population of Leu 3a+, Leu 8- helper T cells was not significantly different, the population of Leu 3a+, Leu 8+ suppressor-inducer T cells was remarkably increased in PBC patients compared to normal controls. On the other hand, no such difference was seen for the NK cells. Furthermore, the Leu 3a+/Leu 2a+ ratio was significantly higher in PBC patients especially in those with a high serum anti-mitochondria antibody titer, which was thought to be due to the decreased population of cytotoxic T cells. PMID- 2589984 TI - [Immunohistochemical study of T cell subsets in lung tissue and in BALF of patients with farmer's lung disease]. AB - The purpose of this study was to ascertain the immunological abnormality of hypersensitivity pneumonitis. The relationship between T cell subsets of lymphocytes in transbronchial lung biopsy (TBLB) specimens and in bronchoalveolar lavage fluid (BALF) were studied in 3 cases of farmer's lung disease (FLD). The lung specimens were examined by immunoperoxidase staining (ABC method) and the cells in BALF by the immunofluorescence method on the flowcytometry. All cases of FLD were diagnosed according to the following criteria: 1) history of exposure to FLD antigen, 2) clinical symptoms (cough, fever, breathlessness), 3) radiologic feature (diffuse small nodular pattern) and functional pattern of interstitial lung disease and 4) evidence of antibodies against Micropolyspora faeni. Histologically, granulomatous interstitial pneumonitis was revealed in all cases. Immunohistochemically, the number of positive lymphocytes was as follows: for Leu 4 (pan T cell) 8.6 cells/15.6 x 10(-3) mm2; Leu 3a (helper/inducer T cell) 5.1 cells; Leu 2a(suppressor/cytotoxic T cell) 1.2 cells on average, respectively. The Leu 3a+ cells were larger in number than the Leu 2a+ cells and the Leu 3a+/Leu 2a+ ratio was 4.76. In the BALF, the percentage of OKT3+ cells (pan T cell) was increased. The percentage of OKT4+ cells (helper/inducer T cell) was higher than that of OKT8+ cells (suppressor/cytotoxic T cell). The OKT4+/OKT8+ ratio was 6.65 in the BALF. The result of this study revealed the close relationship between the numerical distribution of T cell subsets in the lung tissue and in the BALF. It is suggested that the immuno-reaction in the lung tissue of patients with FLD is a type of helper-T cell alveolitis. PMID- 2589985 TI - [The onset and development of allergies in susceptible children. Possibility of their prediction and prevention]. PMID- 2589986 TI - [Application of HPLC to measurement of plasma histamine in bronchial asthma]. AB - We measured the plasma histamine concentration in patients with bronchial asthma by the post-column derivatization method developed by Yamatodani. The mean fasting plasma concentrations of histamine determined for bronchial asthma and control groups (male and female) were 1.93 +/- 0.29 (male) and 1.37 +/- 0.15 (female) pmol/ml and 4.05 +/- 0.69 (male) and 5.19 +/- 0.35 (female) pmol/ml, respectively. The histamine concentrations in the bronchial asthma group were significantly lower than those in the control group, although no significant sex related difference was found. On the other hand, the histamine concentrations in the patients with bronchial asthma after provocation with histamine were significantly higher than when the patients were in a quiescent stable. In this study we can get the behavior of the slight changes in bronchial asthma by considering the finding for the patients, sampling trials and selection of the determination method. PMID- 2589987 TI - [Outbreaks of asthma attacks and meteorological parameters--multivariate analysis]. AB - The correlation between patient visits and meteorological parameters was analyzed among asthmatic children who visited the out-patient emergency clinic at the Teikyo University Hospital during the three years from 1984 to 1986. Data were analyzed with the method of multivariate analysis (quantification theory type II). The major factors affecting the frequency of visits were an air temperature at more than 15 degrees C, a relative humidity at more than 65%, a vapor pressure at more 1013 mb and a wind speed at less than 3.5 m/sec. Multivariate analysis of seven meteorological parameters, the four parameters shown above plus sea level pressure, cloud density and precipitation, revealed that discrimination ratios with the Lag 3, Lag 2, Lag 1 and Lag 0 values were 63.8%, 68.5%, 68.5% and 63.6%, respectively. These results indicate that asthma forecast is possible by the multivariate analysis of meteorological conditions. PMID- 2589988 TI - [The investigation of asthmatic children by multiple factor analysis. I. The relation between severity of asthma and allergic factors]. AB - In a previous study, we analysed the severity of bronchial asthma in childhood by the class II multiple factor analysis method. At that time, the titers of IgE and IgG4 antibodies to the three major food (cow's milk, egg white, and soybeans) and inhalation antigens such as house dust and mites were, however, left unevaluated because of a lack of independence. The quantification of their relative ratios was introduced into the present study, which made it possible to compare their individual potential as risk factors. Exercise induced asthma had the most outstanding effects on the severity of bronchial asthma, followed by counts of peripheral eosinophils and house dust and mites, in this order. Regarding food antigens, the presence of IgG4 and IgE antibody to egg white was the most critical factor, following by titers of IgG4 to cow's milk and soybeans. Complications with atopic dermatitis and allergic rhinitis little affected the severity. Bronchial asthma becomes manifest through a complicated mechanism involving a variety of causative factors. The results given above suggest that the contribution of individual risk factors can be quantified. PMID- 2589989 TI - [A clinical trial of microcomputer software for calculation of aminophylline dosages]. AB - I made microcomputer software for the pharmacokinetic calculation of appropriate administration doses of aminophylline for the treatment of status asthmaticus. It consists of three programs for determination of initial doses, four for determination of maintenance doses, and four for calculation of the pharmacokinetics parameters (Vd, Ke, CL, T1/2). The parameters were estimated 376 times during 151 attacks in 84 patients with bronchial asthma. Vd, Ke, and CL were calculated as below, and the wide variation in the values suggests that individual programs for theophylline therapy should be made for each patient. I concluded that these microcomputer programs were useful in creating an individual administration program. Distribution volume (Vd): 385 +/- 106 ml/kg (n = 115) Elimination rate constant (Ke): 0.155 +/- 0.0878/h (n = 176) Clearance (CL): 61.8 +/- 14.3 ml/kg.h (n = 85) PMID- 2589990 TI - [Successful treatment with continuous intravenous theophylline therapy at home for a patient with problems of oral theophylline absorption]. AB - A 56-year-old male with non-atopic bronchial asthma was admitted to our hospital due to status asthmaticus. His asthma attacks could not be controlled by oral and/or inhalation therapy, but only by intravenous theophylline therapy with corticosteroid. A theophylline absorption test was performed on him after over night fasting. 500 mg of theophylline was administered. The maximum serum theophylline concentration was only 4.0 micrograms/ml at 30 minutes and the urinary one was 13.0 micrograms/ml at 360 minutes after starting the test. The threshold level of absorption from the intestinal tract was higher than the usual level in this patient. We conclude that among patients with intractable bronchial asthma there may be some who have problems with orally administered theophylline. Continuous theophylline therapy at home is recommended for such intractable asthmatics. PMID- 2589991 TI - [The inhibitory effect on passive cutaneous anaphylaxis in guinea pigs of oral administration of Corynebacterium (Rhodococcus) equi]. AB - We studied the inhibitory effect on the PCA reaction of BSA-rabbit anti-BSA (BSA anti-BSA) system in CP-sensitized and CP-unsensitized guinea pigs by the oral administration of C. equi. Strain Ko-85 (Ko-85) cells. The results were as follows: 1) Guinea pigs were sensitized by intraperitoneal injection with the CP. Nine days later, the animals were administered with an oral dose of 80 mg (W.W.) of Ko-85 cells. The animals were submitted daily to PCA reaction tests using BSA and rabbit anti-BSA serum. The inhibition of PCA reaction of BSA-anti-BSA system in CP-sensitized guinea pigs was shown from 4th day to 10th day after administration of Ko-85 cells. The PCA reaction of 9th day was recognized strong inhibition by the oral administration of Ko-85 cells. 2) CP-unsensitized guinea pigs were given an oral dose of 80 mg of Ko-85 cells, and the animals were submitted every other day to PCA reaction tests of the BSA-anti-BSA system. PCA elicited in these animals on the 9th, 15th and 17th days Ko-85 administration were inhibited compared with those in the control animals (which were not given an oral dose of Ko-85 cells). The strongest inhibition was shown in animals challenged on the 15th day after Ko-85 administration. The inhibitory effect of PCA reaction of BSA-anti-BSA system by the oral administration of an oral dose 80 mg (W.W.) of Ko-85 cells was recognized in CP-sensitized and CP-unsensitized guinea pigs. PMID- 2589992 TI - Responsiveness to dietary cholesterol in the domestic fowl is not related to the degree of body fatness. AB - The hypothesis that chickens of a lean rather than a fat line are hyperresponsive to dietary cholesterol was tested. Birds of the fat line showed higher initial plasma total cholesterol levels. The addition of 1% (w/w) of cholesterol to the diet significantly increased plasma cholesterol concentrations but there was no difference in response between the two lines. Dietary cholesterol increased liver cholesterol in both lines, the effect being more pronounced in birds of the lean line. It is concluded that the responsiveness of plasma cholesterol to dietary cholesterol in chickens is not related to the degree of body fatness. PMID- 2589993 TI - Hypocholesterolemic activity of colestipol hydrochloride in SEA quail. AB - Male SEA (Susceptible to Experimental Atherosclerosis) quail were fed a semi purified diet containing 0.5% cholesterol for a period of one week. Colestipol hydrochloride was mixed with the diet at levels of 0.5% and 1.0%. In control animals total serum cholesterol increased from a basal level of 241 mg/dl to 820 mg/dl after one week on the cholesterol supplemented diet. At 0.5% colestipol hydrochloride treated animals experienced a change in serum cholesterol from 223 mg/dl to 528 mg/dl after one week of cholesterol feeding. Colestipol hydrochloride at 1.0% in the diet completely prevented any increase in serum cholesterol in response to the hypercholesterolemic diet. Total serum cholesterols in this treatment group were 258 and 222 mg/dl initially and after the one week treatment, respectively. These data demonstrate that the bile acid sequestrant colestipol hydrochloride clearly prevents the hypercholesterolemia produced by feeding male SEA quail a cholesterol supplemented diet. Based on this activity cholesterol fed SEA quail may be a convenient and practical model for the preclinical evaluation of new cholesterol lowering drugs which act via a mechanism of bile acid sequestration. PMID- 2589994 TI - [The capillary system of the rat heart in occlusion of the coronary artery]. AB - In 74 white rats by means of non-injection++ method morphofunctional state of the myocardial capillary bed has been studied in dynamics at occlusion of descending branch of the left coronary artery. During the first week after the operation blood supply of the areas, adjoining the necrosis, increases at the expense of dilatation and some increase in number of functioning capillaries, that results in enlargement of the exchanging surface and capacity of the capillary bed. Beginning from the 12th day, the value of all these parameters decreases, however, they do not reach their initial level. By the end of the experiment (45 days) the number of the functioning capillaries somewhat decreases, but the capillary diameters remain increased. By that time in the myocardial areas, adjoining the necrosis a parviansiform capillary network without a definite orientation, concerning muscle fibers, has been formed. PMID- 2589995 TI - [Structure of the excretory ducts, intraorganic lymphatic vessels, tissue canals and intercellular space of various organs (data of scanning electron microscopy injection replicas)]. AB - Architectonics of the biliary canaliculi and intrahepatic ducts systems, as well as intraorganic urinary pathways in white rats have been investigated by means of scanning electron microscopy of injection replica. Acinar structure of the intralobular part of the biliary bed has been proved. Anastomoses between the biliary canaliculi of the neighbouring lobules have been demonstrated. A useful method for obtaining injection replica of the intraorganic lymphatic vessels is filling of the ductal system of the parenchymatous organs with solid resins (methylmethacrylate+) under a high (nonphysiological) pressure. Casts of periportal and paravenous hepatic lymphatic vessels have been obtained. An ability of methylmethacrylate to replicate intercellular and connective tissue spaces is verified. Casts of the perisinusoid spaces (Disse) are obtained for the first time. PMID- 2589996 TI - [Changes in the intervertebral disks in disorders of segmental blood supply of the spine]. AB - In 50 mature Chinchilla rabbits a model of chronic insufficiency of blood supply in the lumbar vertebral bodies has been disturbed as a result of unilateral sectioning of the segmentary arteries and veins. By means of light and transmissive electron microscopy the dynamics of structural changes has been followed in tissue of the intervertebral discs for 3 months after the operative intervention. Under hypoxia in the ground substance of the pulposus++ nucleus even proteoglycans granular-filamentous network gradually develops and floccular material and transverse striated filamentous aggregates are accumulated. Notochord cells are subjected to certain degenerative changes and die. Simultaneously fibroblastic cells of the pulposus++ nucleus periphery become activated, they produce glycosaminoglycans and collagen. As a result the hydrated tissue of the pulposus++ nucleus is substituted for a newly formed fibrous cartilage. The process of fibroses in the intervertebral disc is completed in 3 months after blood circulation has been disturbed in the vertebral bodies. PMID- 2589997 TI - [Ultrastructural changes in the skeletal muscles after physical exertion in rats of various ages]. AB - The white rats of the age 1, 3 and 12 months ran in the treadmill at a speed 45 m/min for 20, 40, 60 and 90 days. There is not any linear dependence of muscular transformations and the intensity of physical loading. Changes of the material components of muscular fibers are of undulated character, depending on the age, increase in quantity of myofibrils is always accompanied with a decrease in the quantity of mitochondria. When the total share of myofibrils and mitochondria increases, the quantity of other ultrastructural elements of the muscular fibers and hyaloplasm decreases. PMID- 2589998 TI - [Macro- and microscopic characteristics of the glands of the human trachea and main bronchi in postnatal ontogenesis]. AB - By means of the macro-microscopical method 68 preparations of the trachea and main bronchi, obtained from persons perished and died at the newborn age up to 90 years and having not any disease of the respiratory pathways by the time of death have been studied. The glands in the walls of these organs are adapted to the surrounding structures and have various topography in the cartilagenous and membranous parts of the trachea and main bronchi. The ductal openings in the membranous part demonstrate a regular longitudinal orientation. Despite the fact that during human life the sizes of the trachea and main bronchi increase, the amount of the glands during the postnatal ontogenesis remains nearly at the same or about the same level. With age, the density of the ductal opening arrangement per 1 cm2 of the mucosal membrane surface changes noticeably. Comparing with the newborn age, in the old age this parameter decreases nearly by 4 times. PMID- 2589999 TI - [Quantitative analysis of the bronchial tree structure in dogs and polar foxes]. AB - Bronchial tree in the blue fox possesses a more complex structure that that of the dog and is characterized with a greater length and a greater number of generations in large and middle bronchi with a simultaneous decrease in the number of small bronchiole generations and a greater irregularity and asymmetry within segments. These peculiarities are connected with ecologically ensured in the North demands on increase of anatomically dead space. PMID- 2590000 TI - [Quantitative characteristics of the endocrine cells of the duodenal glands of Carnivora]. AB - In the duodenal glands of the Carnivora investigated endocrine elements have been revealed, a part of them is presented as serotonin-producing EC-cells. Endocrine cells are situated in terminal parts and in glandular ducts, among them elements of open and close types are distinguished. Distribution of these cells in the glandular lobules is subjected to the distal gradient regularity, specific for the gastrointestinal tract mucosal membrane. Amount of endocrinocytes in the glands is much less than in the gut crypts. There is no correlation between distribution of the endocrine cells in the glands and in the crypts. The results of unifactor analysis of variance demonstrate a slight effect of the taxonomic position of the species on the number of endocrine cells in the duodenal glands. The proper endocrine apparatus of the duodenal glands is supposed to produce a local regulatory influence on the secretory activity of exogenic glandulocytes, as well as ensure humoral connections of the duodenal glands with other parts of the gastrointestinal tract. PMID- 2590001 TI - [Status of the detoxication function of the liver after vagal denervation]. AB - In 14 and 25 days of bilateral subdiaphragmatic+ vagotomy perimeter of the endoplasmic reticulum (EPR) of hepatocytes, content of the enzyme (cytochrome R 450) built into the membrane in microsomal fractions, speed of hydroxylation of substrates and oxygen absorption decreased and the section area of EPR and duration of the hexonal sleep increased. The results demonstrate certain disturbances of the detoxication function of the denervated liver. PMID- 2590002 TI - [Pathology of amniogenesis in the early prenatal period of human development]. AB - Morphological and, in a number of cases, cytogenetical investigation has been performed in 420 intact embryonal sacs and in embryos 7-8-week-old, obtained at spontaneous abortions (272) and at tubal pregnancy (148). Among these cases 202 (48.1%) intact empty embryonal sacs, 75 (17.9%) embryos with panorganodysplasia, 25 (6%) embryos with isolated developmental defects and 118 (28%) phenotypically normal embryos have been revealed. Pathology of amniogenesis such as aplasia or hypoplasia of the amniotic cavity is noted in 136 (32.4%) cases. Among 75 embryos with panorganodysplasia anomalies such as hypoplasia of the amniotic cavity in combination with a partial extra-amniotic++ position of the embryos in exocelom (10.7%), aplasia (5.3%) or hypoplasia (17.3%) amniotic peduncle is present in 43 (57.3%) observations. Out of 40 such cases at spontaneous abortions, cytogenetically investigated, in 27 (67.5%) chromosomal disorders (tetraploidy, triploidy, autosomal trisomy and monosomy) are revealed. Aplasia and hypoplasia of the amniotic cavity are considered as pathology of histogenesis at the tissue stage of the early human ontogenesis, that most evidently occurs as a result of asplasia, destruction or anomaly of embryoblast during the first phase of gastrulation on the 7th-11th day of the intrauterine development. PMID- 2590003 TI - [Functional morphology of the supravascular layer of the myometrium]. AB - In the experiment performed on 15 rabbits, action potentials as a group of spikes and separate pick fluctuations have been revealed electrophysiologically in the round ligament of the uterus and the proper ligament of the ovary. In various parts of the myometrial supravascular layer and in the ligaments of the uterus under normal conditions and at leiomyoma nicotinamidedinucleotide-tetrazolium reductase (NADH), nicotinamidedinucleotide-phosphate reductase (NADPH) and alkaline phosphatase activity has been determined both in the myometrial supravascular layer and in the ligaments of the uterus. At leiomyoma NADH activity is elevated, and that of NADPH--decreased in comparison with that in the intact organ. Capillary density in various parts of the myometrial supravascular layer at leiomyoma of the uterus does not noticeably++ differ from that under normal conditions. The data obtained prove the conclusion on a morphofunctional unity of the myometrium and the ligaments of the uterus. By the aggregate of a higher parameters of the enzymes investigated in the area of the posterior part of the isthmus of the uterus, a conclusion is made on a specific functional importance of this part in comparison with others. PMID- 2590004 TI - [A two-step dry-air method of histochemical detection of biogenic amines]. PMID- 2590005 TI - [A method of scanning electron histoautoradiography]. PMID- 2590006 TI - [Realization of the principle of problem-related teaching of histology]. PMID- 2590007 TI - Multiple sclerosis: an unexpected cause of senile dementia. PMID- 2590008 TI - Fragile X syndrome: a genetic etiology for developmental Gerstmann's syndrome. PMID- 2590009 TI - Validity of outcome following stroke rehabilitation. PMID- 2590010 TI - On cerebral metabolism and aphasia. PMID- 2590011 TI - Cerebral cavernous malformations. PMID- 2590012 TI - Neuropsychological differences between the dementias of Alzheimer's and Parkinson's diseases. AB - The question of whether dementia of the Alzheimer type and dementia associated with Parkinson's disease are clinically separable is controversial. We examined possible neuropsychological differences in these two patient groups matched for overall severity of dementia. Patients with dementia of the Alzheimer type had more severe impairment on measurements of memory, language, and orientation, and, unlike patients with Parkinson's disease, there was evidence of apraxia. Patients with Parkinson's disease had more severe impairment related to speed of information processing, and, unlike patients with dementia of the Alzheimer type, they also had disturbance of mood. The nature of visuospatial abnormalities also differentiated the two groups. The pattern of neuropsychological differences is consistent with the cortical-subcortical hypothesis. PMID- 2590014 TI - Impaired recognition of meaningful sounds in Alzheimer's disease. AB - We studied recognition of meaningful nonverbal sounds using a sound-picture matching test in 18 patients with senile dementia of the Alzheimer type (SDAT) and 19 age-matched controls. A significant impairment of sound recognition was found in the SDAT group, consistent with auditory sound agnosia. Although sound recognition performance correlated significantly with auditory verbal comprehension scores, a sound recognition defect was also identifiable in the subgroup of patients with SDAT who had normal verbal comprehension. Qualitative analysis of sound recognition errors revealed that nonaphasic patients with SDAT made predominantly acoustic errors, whereas semantic errors were found almost exclusively in aphasic patients. These findings suggest that the auditory sound agnosia of patients with SDAT may be subdivided into perceptual-discriminative and semantic-associative types. PMID- 2590013 TI - Brain white-matter changes in the elderly prone to falling. AB - Falls and impaired gait are a major source of morbidity in the elderly. Why some elderly become prone to falling is often unclear. We analyzed the gait, equilibrium, and brain computed tomography results of 40 elderly subjects without evidence of neurologic disease known to be associated with falls. Twenty of these subjects were prone to falling and the remaining 20 were nonfalling controls. These two groups were comparable in terms of age and sex (mean age, 83.3 years [SE, 1.7 years]). The group of fallers had significantly worse gait and equilibrium scores and a greater degree of white-matter hypodensity on computed tomography. White-matter hypodensity correlated with impaired gait and equilibrium scores but not with impaired performance on cognitive testing. This study reveals the association of white-matter disease with gait and balance impairment leading to falls in the elderly. PMID- 2590015 TI - Abnormal ocular pneumoplethysmographic results in unilateral neovascular glaucoma. AB - Little is known about the predictive value of ocular pneumoplethysmography in patients with ophthalmic disease. We evaluated eight patients with unilateral increased intraocular pressure due to neovascular glaucoma who did not have evidence of severe extracranial carotid stenosis by duplex scanning and continuous-wave Doppler ultrasound. The ophthalmic systolic pressure measured by ocular pneumoplethysmography was decreased in the affected eye of all eight patients, indicating that neovascular glaucoma may be a cause of abnormal ocular pneumoplethysmographic results. Patients with neovascular glaucoma tended to have larger interocular ophthalmic systolic pressure differences than other patients with false-positive ocular pneumoplethysmographic results by noninvasive criteria. PMID- 2590016 TI - Cortical pathophysiology and clinical neurologic abnormalities in acute cerebral ischemia. A serial study with single photon emission computed tomography. AB - We studied brain cortical radioactive tracer activity in a consecutive series of nine patients with acute hemispheric ischemic stroke at their first cerebral ischemic stroke at their first cerebral ischemic episode. Results from N,N,N' trimethyl-N'- (2-hydroxy-3-methyl-5-[123-I]-iodobenzyl)-1,3 propanediamine-2HCl (four patients) and technetium Tc 99m hexamethylpropyleneamine oxime (five patients) single photon emission computed tomographic studies were compared with x-ray computed tomography (CT) and clinical findings within the first 48 hours, on day 10, and on day 30 after the clinical ictus. Cortical hypoactivity agreeing with the clinical findings was found on all initial scans but not in the follow up studies. Cortical activity on the affected side in patients with stroke was significantly lower when compared with cortical activity in sex- and age-matched controls (n = 21). Computed tomography (with contrast) was less sensitive in detecting the ischemic lesions. These studies demonstrate that in the acute phase of stroke there is a single photon emission computed tomographic cortical disturbance that agrees with clinical findings, even when computed tomography scan infarction is limited to subcortical structures. PMID- 2590017 TI - Middle latency auditory evoked potentials in cortical lesions. Critical of interhemispheric asymmetry. AB - Middle latency auditory evoked potentials after monaural stimulation have been recorded in 16 normal subjects and in 21 patients with unilateral cortical or subcortical lesions determined by computed tomographic scan examination. An interhemispheric index was studied to quantify the asymmetry of Na and Pa middle latency auditory evoked potential components recorded over each hemisphere. This index has been calculated for each ear separately and after adding the responses of both ears. Its reliability is shown to be better in the latter situation. In all of the patients the interhemispheric asymmetry index was in the normal range for the Na component. For the Pa component this index was abnormal in 11 patients with cortical temporal lobe or subcortical lesions interrupting acoustic radiations. These results confirm that the Pa is dependent on the integrity of acoustic radiations and auditory cortex in the supratemporal plane, whereas the Na component would be generated at a subcortical level. Unilateral extinction of the dichotic listening test was found to correlate with abnormal Pa component asymmetry in the case of lesions involving the auditory structures. PMID- 2590018 TI - Evidence for transhemispheric diaschisis in unilateral stroke. AB - Nineteen patients with strictly unilateral ischemic stroke as determined by clinical examination, computed tomography, magnetic resonance imaging, and standard angiography underwent cerebral blood flow (CBF) analysis using fluorine 18 fluoromethane and positron emission tomography. Mean flow values for averaged hemispheric, infarct, and homologous contralateral regions of interest (ROIs) were determined. All patient CBF values were significantly below comparable CBF ROIs in neurologically normal controls using Wilcoxon's two-sample rank testing. Multiple regression analysis disclosed a significant correlation between contralateral CBF are both localized CBF in the infarct ROI and patient age. Correlations between contralateral CBF and dependency score or severity of neurologic deficit at time of positron emission tomography, expired PCO2, mean arterial blood pressure, serum glucose or hematocrit, risk factor score, and number of days studied after stroke were not statistically significant. Although we did not identify the biologic mechanisms involved, we conclude that CBF reduction contralateral to a strictly unilateral ischemic infarction is due to a combination of aging and transhemispheric diaschisis. PMID- 2590020 TI - The 1985 National Ambulatory Medical Care Survey of neurologists. A clinician's perspective. PMID- 2590019 TI - Correlates of headache in a population-based cohort of elderly. AB - Data from a community-based study of 3811 persons aged 65 years and older were used to describe the characteristics of headache in the elderly. Subjects were asked whether they experienced headache in the past year, the frequency and severity of their headaches, and whether they experienced three symptoms of migraine: unilaterality, nausea or vomiting, an aura preceding the headache. Prevalence of headache in those aged more than 65 years declined with age in both men and women; women had a higher prevalence in each age group. The same was true for frequent, severe, and migrainous headache. We examined age- and sex-adjusted correlations of headache with several medical and social factors. Prevalence of any headache was strongly associated with joint pain, depression, bereavement, waking during the night, use of eyeglasses, symptoms of temporomandibular joint dysfunction, and self-assessment of health. Similar variables were associated with frequency, severity, and migrainous symptoms, and thus could not be distinguished among these various types. PMID- 2590021 TI - Vertical one-and-a-half syndrome. Supranuclear downgaze paralysis with monocular elevation palsy. AB - A patient with bilateral infarction in the mesodiencephalic region showed impairment of all downward rapid eye movements (including vestibulo-ocular movements) and foveal smooth pursuit (nondissociated downgaze paralysis) associated with monocular paralysis of elevation (vertical one-and-a-half syndrome). Bell's phenomenon and all types of horizontal eye movements were preserved. The lesions may have affected the efferent tracts of the rostral interstitial nucleus of the medial longitudinal fasciculus bilaterally and the premotor fibers to the contralateral superior rectus subnucleus and ipsilateral inferior oblique subnucleus, either before or after decussation in the posterior commissure. PMID- 2590022 TI - Proceedings of the First European Congress of Oto-Rhino-Laryngology and Cervico Facial Surgery. Paris, 26-29 September 1988. Selected papers. PMID- 2590023 TI - Melanin in the inner ear. An experimental study with control and kanamycin intoxicated colored guinea-pigs. AB - Following several studies on the effects of kanamycin toxicity on the inner ears of guinea pigs, we have studied the importance of melanin in this phenomenon. Transmission electron microscopy showed that, under the influence of kanamycin, the intermediate strial cells developed a secretory aspect similar to that seen in skin melanocytes. This aspect as yet has never been described for the inner ear cells. A planimetric, morphometric method was also used to determine the strial cell melanin status in control animals. Additional findings in the study confirmed an increase in the number of melanosomes during kanamycin poisoning. Statistical data are discussed. PMID- 2590024 TI - Saccular afferent fibers to the cochlear nucleus in the guinea pig. AB - After tracing the vestibular nerve of the guinea pig with horseradish peroxidase (HRP), a conspicuous fiber bundle was found that passed to the ipsilateral cochlear nucleus. HRP-labeled fibers were seen to leave the descending vestibular nucleus at a level caudal to subgroup "y" in a lateral direction. Travelling close to the restiform body, the axons terminated at cells lying between the dorsal and posteroventral cochlear nucleus. These cells could be distinguished cytoarchitecturally from surrounding cells of the cochlear nuclei. Several electrophysiological investigations have assumed that there is a direct connection between the vestibular and the cochlear system. Compared to these, the fibers under consideration might be the morphological basis for such a "vestibulo cochlear anastomosis." PMID- 2590025 TI - Primary vestibular projections in the chinchilla. AB - The central projections of fibers from the vestibular nerve were studied in 19 chinchillas after horseradish peroxidase labelling. In addition, the limits of the vestibular nuclei and the anatomical characteristics of their neurons were also studied. All five vestibular nuclei received primary afferents, but there were extensive areas of them that received very little or no projections at all, such as the rostral part of the superior vestibular nucleus, the dorsocaudal part of the lateral vestibular nucleus, the caudal half of the medial vestibular nucleus and the caudalmost aspect of the dorsal vestibular nucleus. PMID- 2590026 TI - The properties of spontaneous and evoked acoustic emissions in neonates and children: a preliminary report. AB - Evoked acoustic emissions (EAEs) and spontaneous acoustic emissions (SAEs) recordings hold some promise as a fast, objective and non-invasive audiological procedure, especially in children. However, accurate interpretation in the emission response must be based on the basic properties of the emissions present in a younger age group. In so doing, the properties of emissions were investigated in 49 ears from 26 children, whose ages varied between 2 days and 10 years. EAEs could be recorded in all normal ears, but the incidence of long duration EAEs decreased with age. There were no statistically significant variations in recording the EAEs detection threshold with age. The incidence of SAEs also decreased with age. PMID- 2590027 TI - Auditory frequency selectivity and tinnitus. AB - In the majority of cases tinnitus has a high pitch and can be matched rather precisely to an objective high frequency sound. However, it is well known that tinnitus can be masked by different tones without any frequency selectivity. We wondered whether objective tones matched to tinnitus would show a more significant deterioration of frequency selectivity than could be expected from any associated hearing loss. Psychoacoustic tuning curves were obtained using simultaneous pure-tone masking and revealed a broadening of frequency selectivity. In cases of comparable bilateral hearing losses with unilateral tinnitus, the broadening associated with the tinnitus was particularly conspicuous. This broadening strongly suggests that tinnitus originates in the cochlea, although some involvement of central pathways may also occur. Tinnitus induced broadening of frequency selectivity as a possible sign of cochlear origin deserves further consideration in future studies. PMID- 2590029 TI - Computed tomography in the study of the eustachian tube. AB - A CT study was made of the eustachian tube in normal subjects as a control group and patients with chronic pathological inflammation of the middle ear. CT made it possible to perform contiguous scans at homologous depths of 1.5 mm, showing the whole interior of the tube in clear detail: the protympanum, the bony and cartilaginous portions, and the nasopharyngeal orifice. In most of the cases of pathological middle ear inflammations, the eustachian tube lumen was seen to be constricted and obstructed with isodense matter. Our present results also show the importance of extending CT investigations beyond the tympanic cavity and the mastoid to the eustachian tube in order to have more clinical data on its condition. PMID- 2590028 TI - Endoscopy of the eustachian tube: use of the fiberscope and the telescope. AB - The necessity for direct observation of the pharyngeal outlet of the normal or pathological eustachian tube has always stimulated research for suitable diagnostic instruments. As the result of various investigation procedures currently available, we performed a series of endoscopic screenings using both the Hopkins telescope and the fiberoptic rhinopharyngolaryngoscope. The present study aimed at evaluating and demonstrating the morphological and dynamic functional condition of the pharyngeal outlet of the tube. The present investigation was carried out on 60 males and females, ranging in age from 4 to 70 years. Inspection of the pharyngeal outlet of the tube and its adjoining region enabled us to document some of the various causes for tubal dysfunction. By visualizing tubal movements, endoscopy also made it possible to perform a dynamic study of tubal functions. However, the investigation procedure utilized did not allow us to record any significant differences between the two diagnostic instruments used, except that the fiberscope can be more easily handled, whereas the photographs taken with the telescope are of better quality. PMID- 2590030 TI - Radiological studies in trigeminal nerve pathology. AB - The authors have used CT scans and MRI to study pathology in anatomical and radiological correlations of brain slices. The CT scan was particularly useful for studying structures at the skull base, although at the level of the posterior fossa such scans could visualize only those tumors that were larger than 8 mm. even after injection. The CT scan was found to be the most useful examination before surgery for facial neuralgia. In contrast MRI gave a precise cisternal course of the trigeminal nerve and its relations with vascular structures. PMID- 2590031 TI - Magnetic resonance investigations of non-acoustic petrous lesions. AB - Twenty cases of intrapetrous lesions were studied by a 1.5 T magnetic resonance (MR) unit. In all cases, comparisons were made between MR, CT and clinical findings. Our present material included 9 cholesteatomas, 1 cholesterol cyst, 3 primary epidermoid carcinomas, 2 metastatic neoplasms, 1 glomus jugulare tumor and 4 facial neurinomas. Gadolinium was injected in 7 cases and seemed to be the best method for studying the intrapetrous tumors. MR permitted accurate topographic study and assessment of tumoral extension, as well as a ready demonstration of tumor vascularity. The present findings also showed that MR is not capable of defining small bony detail or calcifications. PMID- 2590032 TI - Gentamicin and other ototoxic antibiotics for the transtympanic treatment of Meniere's disease. AB - Severe unilateral cases of Meniere's disease can be successfully treated with ototoxic antibiotics. Among them gentamicin sulfate gives the safest results. With the aid of a small syringe this antibiotic is introduced into the external auditory canal 5 times/day. From there it reaches the middle ear through a ventilating tube by using a Politzer bag. Gentamicin then penetrates the round and oval windows, where it influences inner ear function. Of 92 patients treated during the past 20 years, more than 90% have had no further attacks after therapy. PMID- 2590033 TI - Anatomical and surgical particularities of cholesteatomas in children. AB - In children, cholesteatoma is closely related to dysfunction of the eustachian tube and evolves inside a malleable temporal bone. The importance of auditory and speech functions in such patients has caused us to use a very particular clinical philosophy. At the present time we have studied 154 cases of cholesteatomas in children under 15 years old. The following three points have been shown: the pathogenesis of a cholesteatoma can be of the primary type, secondary (due to an unfavorable extension of retraction pocket or to squamous cell migration) or even be iatrogenic; anatomical and clinical findings (with X-ray studies) predicate the treatment used; surgical treatment frequently requires a "second-look" operation. PMID- 2590034 TI - Surgical control of the mastoid segment in chronic ear disease in 1988. AB - The basic surgical guidelines for mastoid segment control are described in chronic ear disease. Dense cortical bone pate and mastoid tip bone chips are collected for possible obliteration of the surgical cavity produced. A meatally based musculoperiosteal flap is raised if "canal wall-down" surgery is anticipated. Mastoid bone surgery must be meticulous and the sigmoid, cerebellar and dural plates are first exposed. This is followed by a perilabyrinthine dissection. Tympanic or epitympanic surgery is connected with mastoidectomy as needed. All cavities are then obliterated. PMID- 2590035 TI - Our experiences at Semmelweis University with different techniques and materials in the surgery of chronic otitis media. AB - Different techniques and materials used in the surgery of chronic otitis media have been evaluated in a large clinical experience at Semmelweis University, Budapest. Data from 1572 operations performed during the last 5 years (1983-1988) are summarized. In the 870 non-cholesteatomatous processes (55.3%), mastoidectomies and tympanoplasties were performed, with the latter primarily using temporalis fascia and cortical bone. Out of the 250 cholesteatoma cases (15.9%), one-fourth was solved by a primary wall-up technique followed by a second stage revision and tympanoplasty within 1.5 years later. PMID- 2590036 TI - Sensorineural high-frequency hearing loss after drill-generated acoustic trauma in tympanoplasty. AB - Tympanoplasty can cause a sensorineural hearing loss by a mechanism of acoustic trauma. Although this lesion appears to be relatively infrequent in clinical practice, we believe that its low apparent incidence is caused when clinicians fail to assess the auditory frequencies above 8000 Hz. Twenty-four patients with normal bone-conduction audiometric thresholds scheduled for tympanoplasty were assessed with an electro-stimulation, bone-conduction high-frequency audiometer which can measure hearing frequencies up to 20 kHz before and after surgery. A measurable hearing loss was found in the upper limits of the audible frequencies in 9 patients (37.5%), and was considered important in 4 of them (16.7%). This hearing loss was recorded above the upper frequency limit of conventional audiometers. The findings in this study indicate that drilling of the temporal bone can impair the hearing level in the high frequencies in a significant number of patients. High-frequency audiometry is a very sensitive tool to assess any damage caused to the inner ear by surgical procedures carried out in the middle ear and temporal bone. PMID- 2590037 TI - New perspectives on lyophilized bone allografts. AB - In 1987, at the Congress of Implants in Otology in Venice, Italy, we first presented our experiences with stored lyophilized bone allografts for reconstruction of the tympano-ossicular chain. Since then, we have extended our experiences to include reconstruction of the external bony ear canal, the filling of defects in the mastoid bone, reconstructive nasal surgery and rehabilitation of major bony defects of the face. Additionally, we have tried to improve the preparation of the bony implants used clinically and have started a multicenter collaboration with other European universities. PMID- 2590038 TI - Modern diagnostic strategy for acoustic neuromas. AB - We have reviewed the most recent 120 cases of acoustic neuromas operated upon in Bordeaux, France. In so doing, we have defined the strategy required to reach an accurate diagnosis as essentially comprising three stages. The first of these is to understand that the presenting symptom complex may be typical with progressive unilateral hearing loss, tinnitus, etc., or atypical with sudden hearing loss (10%), recovering facial paralysis (3.3%) or a Meniere's syndrome (3.3%). Included in the first stage of diagnosis are audiovestibular investigations. An absent stapedial reflex was noted in 41% of our cases and an abnormality in vestibular testing in 95% of cases tested. These findings would be clear indicators to proceed to the second stage of the diagnostic strategy. This second stage comprises electric response audiometry consisting of auditory brainstem response (ABR) testing and electrocochleography (ECochG) employed as a filter for determining which patients should proceed to the third stage of testing. A combination of ABR and ECochG provides the clinician with results of high sensitivity and specificity. The false-negative rate for combined results in our experience has been less than 1%. The final diagnostic stage is radiological imaging, in particular using magnetic resonance imaging (MRI) with gadolinium contrast as the modality of choice. MRI is superior to CAT scanning, especially in the diagnosis of stage I intracanalicular tumors. PMID- 2590039 TI - The translabyrinthine approach for the removal of large acoustic neuromas. AB - The results and the sequelae are reported from a series of consecutive 400 translabyrinthine removals of acoustic neuromas comprising almost all such tumors in Denmark during a 12-year period from 1976 to 1988. There were two intrameatal, 137 median-sized, 112 large and 149 advanced tumors, the latter having a diameter exceeding 40 mm. The mortality rate in the overall series was 2%. The incidence of cerebrospinal fluid leak occurred in 11%, and persisted for more than 2 weeks in 4%. Facial nerve function was completely normal in 67% of the patients, while only 5% required a nerve anastomosis. PMID- 2590041 TI - The enlarged middle cranial fossa approach for surgery of the temporal bone and of the cerebellopontine angle. AB - Due to the fact that the temporal bone has broad segments of bone anterior to and behind the internal auditory canal which are empty of functionally important structures, a broad exposure of the cerebellopontine angle may be obtained from above. This technique is adequate for the management of acoustic neurinomas up to 3 cm in diameter. A low postoperative morbidity and a high percentage of hearing preservation with total tumor removal were obtained in a series of 190 cases. This report underlines the advantages of the procedure and points to various other indications. PMID- 2590040 TI - Experiences at the Timone Hospital, Marseille in acoustic neuroma surgery. AB - The authors report their experiences after operating on 279 patients with unilateral acoustic neuromas between 1976 and 1988, with 258 cases managed by the translabyrinthine approach and 21 cases by the middle fossa approach. The authors emphasize the necessity for total removal in order to avoid recurrences. PMID- 2590042 TI - Facial reinnervation after facial paralysis: is it ever too late? AB - Following Conley's work on facial nerve cross-over surgery in long-standing facial paralysis, we have reviewed five cases of paralysis of 2.5-7 years' duration. All had complete absence of electrical activity on preoperative EMG and ENG studies. In four of the five cases the facial nerve was not severely atrophic and a "cross-over" technique was feasible. Post-operatively, the results were electrically and clinically good to excellent. To foresee the results of facial nerve cross-over surgery, we have found that the degree of atrophy of the affected nerve at the time of reconstructive surgery is a more important factor than the time lapse since the beginning of the paralysis. Those results also seem better in younger patients. Our findings suggest that hypoglossal-facial cross overs be considered even 3 years after a paralysis, mostly in younger patients, when the nerve is not severely atrophic. In some cases this technique can be complemented by muscular transfers or selected cosmetic surgery. PMID- 2590044 TI - Experimentally induced sinusitis: the importance of vasomotor regulation. AB - An acute pneumococcal maxillary sinusitis was induced in New Zealand white rabbits by unilateral obstruction of the sinus ostium and then injecting 10(8) Streptococcus pneumoniae into the sinus. After subjecting this bacterial strain to one animal passage, the bacteria were reisolated in nine of ten infected maxillary sinuses. All rabbits developed a unilateral purulent sinusitis, while a non-purulent sinusitis could be induced by occlusion only of the maxillary ostium. By using a non-diffusable tracer, microspheres labelled with Sn113, blood flow measurements were performed on these sinuses. These studies showed that the blood flow of the infected sinuses was significantly higher than on the control side. However, in chronic sinusitis (with a blocked ostium), the blood flow did not differ significantly from that on the control side. Biochemical studies in the animals with purulent sinusitis demonstrated that lactate concentration in the mucosa was significantly higher as compared to the control side. The glucose concentration was significantly lower in the mucosa of the infected side, as was the ATP content of the sinus mucosa in purulent sinusitis. These results indicate an increased glycolysis as well as a relative energy depletion in the sinus mucosa in purulent sinusitis, which could result in an impaired epithelial function. PMID- 2590043 TI - The preservation and regeneration of cilia on human nasal epithelial cells cultured in vitro. AB - Dissociated human nasal epithelial cells from nasal polyps were cultured in Ham's F12-DME 1/1 supplemented with NU-serum 10%, choleratoxin (10 ng/ml), retinoic acid (10(-7) M) and antibiotics. In monolayer cultures, the epithelial cells grew to confluency on collagen gels, became squamous, and lost their cilia within 2-6 weeks. In suspension cultures, epithelial cell sheaths formed stable vesicles and aggregates. These maintained a respiratory-type morphology and normal ciliary activity for over 6 months. When deciliated, squamous cells from monolayer cultures were brought in suspension, a respiratory-type morphology with cilia reappeared. This in vitro ciliogenesis resulted in normal and coordinated ciliary activity observed for more than 5 months. PMID- 2590045 TI - Parathyroid surgery in primary hyperparathyroidism: an update. AB - The best approach to parathyroid removal in primary hyperparathyroidism (HPT) is still a major topic in neck surgery. The present report reviews our experiences with 71 patients operated by parathyroidectomy (PTX) between 1978 and 1987. Preoperative computed tomography, sonographic and double-tracer subtraction scanning examination allowed a precise assessment of the number and the topography of the diseased glands. Consequently, 65 patients underwent partial "selective" PTX, with removal of one or two glands, while 6 patients underwent subtotal PTX. The surgical results can be summarized as follows: full success in 67 cases (94.4%); persistent hypercalcemic syndrome in 3 cases (4.2%); recurrence of HPT in 1 case (1.4%). One case of persistent hypercalcemia was solved by reoperation. Thus, the total success rate was definitively assessed at 95.8%. As a complication of surgery a long-lasting postoperative hypocalcemic syndrome was observed in only 2 patients following subtotal parathyroidectomy. Our overall findings show that an attentive preoperative study by means of modern imaging techniques usually allows a "selective" partial PTX with good results and a low risk of complications. PMID- 2590046 TI - The relationship between nuclear DNA content in salivary gland tumors and prognosis. Comparison of mucoepidermoid tumors and acinic cell tumors. AB - Differences in prognosis between salivary gland mucoepidermoid tumors and acinic cell tumors were compared by means of conventional histopathological grading and nuclear DNA content which was assessed cytochemically by a scanning cytophotometric procedure. The mucoepidermoid tumors were found to show a stronger correlation between histopathological grading and prognosis than did the acinic cell tumors. By using DNA quantification, valuable additional information could be obtained for predicting the behavior of the mucoepidermoid tumors, whereas there was no correlation between DNA content and prognosis for the acinic cell tumors. Regarding the relatively "benign" clinical course of most mucoepidermoid tumors, the term "tumor"--as proposed by the World Health Organization's classification--seems appropriate. In contrast, the more severe clinical courses of the acinic cell tumors justify the use of the term "carcinoma" instead. PMID- 2590047 TI - Normovolemic hemodilution in head and neck surgery. AB - As the transfusion risks to which patients are exposed are gradually understood, every effort is being made to find both a valid and safe alternative to homologous blood transfusions. Bearing this in mind, the most sensible solution appears to be the practice of a self-donor procedure with normovolemic hemodilution prior to elective surgery. However, even repeated bloodlettings do not modify the oxygen delivery to tissues since, with a reduction in the hemoglobin content of the circulating blood, there is a corresponding increase in oxygen availability. Since the reduction of circulating erythrocytes brings with it a reduction in blood viscosity, there is in turn an improvement in the microcirculation. The generally better tissue oxygenation, the reduction of the blood's viscosity and the increased circulatory perfusion all also favor a prophylaxis against deep vein thrombosis. We have currently performed 72 surgical procedures for head and neck neoplasms that were undertaken at the Clinical ENT Division of Treviso Hospital precisely with the normovolemic hemodilution described above. The self-donor transfusion technique was adopted with the help of the hospital's transfusion service. We have analyzed the data relative to this method and have found that the normovolemic hemodilution represents the treatment of choice in surgery-induced stress, particularly since this approach allows a better tissue oxygenation. PMID- 2590048 TI - Surgical treatment of laryngotracheal stenosis in infants and children. AB - Laryngotracheal stenosis in children is difficult to manage, especially in cases of acquired lesions. Of 317 cases reviewed, 75 surgical cases are reported here: 28 were congenital and 47 acquired, mostly due to endotracheal intubation. A large variety of laryngotracheoplasty techniques have been used in reconstruction, depending on the age and status of the patient, the size of the laryngeal lumen, the exact site of the stenosis and any associated anomalies. The three main techniques used have been described by Evans, Cotton, and Rethi. Stenting relied on Silastic rolls, Montgomery T-tubes and Aboulker Teflon prostheses. The results in 65 patients showed a decannulation rate of 92% in cases of congenital stenosis and 80% in acquired ones. Improvements in therapy still seem necessary in order to reduce the cannulation time following treatment and the sequelae producing dysphonia. PMID- 2590049 TI - Experience with the home-care of tracheotomised paediatric patients. AB - Many infants with tracheotomies remain cannulated for prolonged periods while the underlying cause of airway obstruction is either treated or natural resolution is awaited (usually by growth). To enable these children to enjoy a relatively normal family environment despite a tracheotomy, it is desirable that they should be managed at home for at least part of the time. For the past 8 years we have routinely used soft polyvinyl chloride paediatric tracheotomy tubes (Shiley) in our patients. These tubes have proved to be relatively resistant to obstruction with secretions and are changed at 1- to 2-week intervals. They can be modified by making a series of three to four 2-mm through-and-through fenestrations around the shoulder in order to improve speech production and facilitate decannulation. Parents are tutored in tracheotomy care, which includes tube changing, humidification and suction. They are then permitted to take their child home from hospital when they are considered to be competent. Twenty-eight children (13 boys, 15 girls) with a mean age of 14.5 weeks (range 1-525 weeks) at the time of tracheotomy have been managed at home using this system. The median period of hospitalisation was 12 weeks (range 5-75 weeks), and the median duration of home management was 94 weeks (range 13-394 weeks). Sixteen patients have been successfully decannulated, 11 remain cannulated and 1 died at home from sudden infant death syndrome. Despite supportive measures, the majority of the children developed intermittent chest infections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590050 TI - Aesthetic surgery for microtia. AB - We describe here a technique for reconstruction of the external ear based upon an autogenous costal cartilage graft which is inserted into a cutaneous pocket dissected in the auricular area. Three subsequent procedures are then performed: rotation of the ear-lobe; reconstruction of the tragus; and elevation of the auricle. The ideal age for reconstruction is about 7 years. This technique was originally described by Brent, who has a very extensive experience with this kind of surgery. Skin deficiencies can be overcome by using either a temporo-parietal fascial flap or a skin expander. PMID- 2590051 TI - Different technical approaches for blepharoplasty in eyelid rejuvenation surgery. AB - The authors have reviewed their clinical experiences with 92 cases of blepharoplasties treated during the past 10 years and discuss the principal approaches used, depending on the age of the patient, the amount of adipose tissue present, the degree of lower lid tarsal and muscle laxity present, and the quality of the skin excess encountered. On the upper eyelid, skin excision is combined with an orbicular muscle strip and in older patients a suspension of the lateral canthus. On the lower eyelid the transconjunctival approach is emphasized in young and or colored patients, using an undermined musculocutaneous flap in the classical technique. A good choice between these different approaches avoids the rare complications of ectropion and scleral show because the procedure used is considered to be a variable "geometric" operation. PMID- 2590052 TI - The diagnostic role of fiberoptic bronchoscopy in AIDS patients with suspected Pneumocystis carinii pneumonia. AB - Fiberoptic bronchoscopy was carried out in 17 consecutive AIDS patients with suspected opportunistic infections. A total number of 23 bronchoscopies were performed and a comparison was made about the effectiveness of the available diagnostic techniques, which included bronchoalveolar lavage, transbronchial lung biopsy and bronchial brushings. The most common cause of pulmonary parenchymal disease was Pneumocystis carinii (7 patients). In 6 of these HIV-positive patients the detection of infection was decisive in making a diagnosis of AIDS. The most effective procedure for diagnosing P. carinii pneumonia was transbronchial lung biopsy (5 patients), while bronchoalveolar lavage and bronchial brushings showed P. carinii and 5 and 4 patients respectively. Complications were minor and occurred only in those patients subjected to transbronchial biopsy. Our findings showed that transbronchial biopsy has the highest yield in the diagnosis of P. carinii infection. When all diagnostic components of the bronchoscopic procedures are carried out, very few cases with these infections should be missed. PMID- 2590053 TI - The use of microfluorometry to study DNA in nasopharyngeal carcinomas: a possible prognostic tool? AB - A microfluorometric method was used to determine the nuclear DNA content in the nasopharyngeal carcinomas (NPC) of 25 patients treated before 1983. Eleven patients are still alive with no evidence of disease (NED), while the rest died of their disease (DOD). All of the patients received a cycle of radiotherapy, while some also received chemotherapy or neck dissections. The neoplastic cells studied were taken from the original biopsy blocks, deparaffinized, isolated by enzymatic treatment and mechanical fragmentation, and then Feulgen-stained. The cytofluorometric measurement was carried out by a microphotometer equipped for fluorescence excitation and connected to a computer. This method allowed us to construct a histogram of the DNA content in the neoplastic cells. Different neoplastic classes were identified and represent the heteroclonality of the tumor, which can be expressed by the heteroclonality index (HCT). From the collected data it appears that the NED patients all had a low HTC (less than 1) and only 7 of the DOD patients had low HTCs (less than 1). Six of the DOD patients with a low HTC were in advanced stages of their tumor at the time of diagnosis, while the remaining patient did not complete his treatment. Our results show that the DNA analysis of the NPC cell population may offer a useful tool in predicting the biological behavior of this tumor and also improving its treatment. PMID- 2590054 TI - Carcinoma of the face: aspects of tumor surgery and operative technique. AB - Free grafts, regional or myocutaneous flaps, microvascular tissue transfer and prosthetic rehabilitation are essential techniques required for modern reconstruction of defects in the head and neck. The myocutaneous flaps and the microvascular grafts especially offer a wide variety of tissues useful for reconstruction. It is our belief that a microsurgical team should be organized in every major ENT department for interdisciplinary cooperation depending on the local situation. PMID- 2590055 TI - Cancer of the laryngeal vestibule. A retrospective study of 161 cases. AB - We report a retrospective study of 161 cases of vestibular or epilaryngeal cancer treated by horizontal laryngectomy. The different factors affecting prognosis were analyzed statistically. Three groups were distinguished according to the size and primary site of the tumor: (1) a group with a very poor prognosis, which included patients with large tumors of the epilarynx; (2) a group with an average prognosis, which included small tumors of the epilarynx and large tumors with their primary site in the vestibule; (3) a group with a favorable prognosis which included tumors classified as T1 or T2 that were initially located in the vestibule. PMID- 2590056 TI - Results of laryngeal cancer surgery in four ENT centers in poland. AB - The results of laryngeal cancer surgery were assessed in a group of 832 patients treated in four major ENT centers in Poland. Five-year survival rates were as follows: stage I, 86%; stage II, 71%; stage III, 54%; and stage IV, 42%. In experienced hands and for properly selected cases, cure rates after partial (conservation) laryngeal surgery were similar to those after total laryngectomy. For early stages (I and II), the survival after partial surgery was better than that found after radiotherapy. PMID- 2590057 TI - Coloplasty and free intestinal transplants in the treatment of extensive cancers of the pharyngo-oesophageal junction. AB - The authors report their surgical experiences with 55 extensive tumours of the pharyngoesophageal junction. Thirty-three of these cases were managed by circular pharyngolaryngectomy, total oesophagectomy with stripping and left coloplasty, and 22 were treated with circular pharyngolaryngectomy with free intestinal transplants. A comparative study of the post-operative courses of the patients and their oncological and functional outcomes shows the advantages, disadvantages and indications of these two techniques. PMID- 2590058 TI - An interdisciplinary research project on language acquisition during the first 3 years of life. AB - The authors report their preliminary findings in a prospective study on the possible effects of different risk conditions present at birth on language acquisition and cognition. A multifactorial test was used to test normal children for normative values. This test was then administered to 186 at-risk babies and controls at 18 months of age. A noticeable difference in overall performance was observed only for preterm babies having an appropriate weight for their gestational age. However, significant results will only be available after evaluations are repeated when the children are 36 months old. PMID- 2590059 TI - New surgical techniques for voice improvement. AB - Laryngeal framework surgery for improving or changing the voice is a challenging development in phoniatric surgery. Basically two categories can be distinguished: (1) attempted medialization of the vocal fold, as for the treatment of paralytic dysphonias (arytenoid rotation technique and Isshiki's type I thyroplasty); (2) adjustment of the vocal fold's tension to produce changes in vocal pitch, as for the treatment of transsexuals or mutational dysphonia (cricothyroid approximation, Isshiki's type III thyroplasty and LeJeune's anterior commissure laryngoplasty). Both types of surgery are best performed with the patient under local anesthesia so that fine tuning of the voice is possible by monitoring the voice during the surgical procedure. The techniques of arytenoid rotation and Isshiki's type I thyroplasty are described in detail and the result of a combination of these procedures is illustrated by a case history of an aphonic patient with unilateral vagus nerve paralysis and subsequent severe incomplete glottal closure during phonation. In addition, the results achieved in several other patients are presented. Our current experience with laryngoplastic surgery and its variations is such that endolaryngeal Teflon or collagen injections are no longer used in our department. To date, we have seen no complications from the laryngoplasties and the voice results have been excellent. PMID- 2590060 TI - Initial long-term results of collagen injection for vocal and laryngeal rehabilitation. AB - The records of 14 patients who have benefited from intralaryngeal injections of ZCI collagen for at least 3-4 years were reviewed. All patients still living were evaluated. Qualitative phonatory measurements included laryngostroboscopy and frequency voice analysis, while quantitative studies included maximum phonation times and phonatory quotients. The absence of both local and general inflammatory reactions was observed in these patients, confirming the excellent host tolerance of ZCI collagen and the stability of the functional results achieved. PMID- 2590061 TI - Factor VII assays, plasma triglyceride levels, and cardiovascular disease risk. PMID- 2590062 TI - Increase in endothelial cell density before artery enlargement in flow-loaded canine carotid artery. AB - To investigate the morphologic basis of blood flow-dependent adaptive vascular enlargement, we quantitated endothelial cell density, dimensions, and structure in canine carotid arteries that were flow-loaded for 4 weeks, i.e., just before the development of significant adaptive enlargement. Increased flow was produced in the right common carotid artery of seven adult beagle dogs by an arteriovenous shunt to the right external jugular vein. The left common carotid artery was used to produce sham-operated controls. Five additional animals were used to produce sham-shunted controls, and two dogs were used as nonoperated controls. The blood flow rate (BFR) and wall shear rate (WSR) were markedly increased immediately after anastomosis in the proximal segment of the shunted artery (BFR = 719 +/- 142 ml/min, WSR greater than 4127 +/- 1002/sec) and after 4 weeks (BFR = 628 +/- 157 ml/min, WSR greater than 2919 +/- 388/sec) compared to the same artery before anastomosis (BFR = 154 +/- 50 ml/min, WSR = 904 +/- 314/sec, p less than 0.01 x 10(-3) for both comparisons) and to the contralateral control artery after 4 weeks (BFR = 365 +/- 110 ml/min, WSR = 2136 +/- 876/sec, p less than 0.01 and p less than 0.05, respectively, compared to the shunted side). In the shunted artery, endothelial cell density was markedly increased (6.15 +/- 0.68 x 10(3) cells/mm2 compared to 3.33 +/- 0.70 x 10(3) cells/mm2 for the controls, p less than 0.001). Endothelial cells on the high flow side were markedly narrowed in both axial and circumferential directions, but were radially thickened; nuclei became prolate-spheroid in shape. On the control side, cells were relatively flat and thin. We conclude that elevated wall shear stress induces an early increase in endothelial cell number and that this increase precedes the development of significant blood flow-dependent vascular enlargement. PMID- 2590063 TI - Effect of stenosis on wall motion. A possible mechanism of stroke and transient ischemic attack. AB - The mechanism by which atherosclerotic plaque causes stroke and transient ischemic attack is not fully understood. One possibility is that the plaque stenosis may set up hemodynamic conditions causing local arterial wall collapse. Arterial wall collapse may, in turn, affect the integrity of the plaque. This study was designed to define the effects of stenosis on the production of arterial wall collapse using a latex tube model. Stenoses ranging up to 81% by diameter were tested in a Starling resistor chamber under pulsatile pressure conditions upstream of the tube. Increasing the degree of stenosis progressively decreased the external pressure necessary to produce collapse, from 37 mm Hg with the 0% stenosis to 24 mm Hg for the 81% stenosis. The stenoses greater than 70% produced a new phenomenon of "systolic wall collapse" just distal to the stenosis. The maximum diameter decrease was 2.83 mm from the baseline diameter of 6.41 mm. Cyclic wall motion just downstream of the stenosis increased with the increased degree of stenosis from 0.34 mm at 0% stenosis to -1.28 mm at 75% stenosis. The phenomena are discussed in terms of simplified Bernoulli pressure drops. We conclude that local arterial stenosis can produce conditions favorable for wall collapse and increased wall motion at physiologic pressure and flow. This collapse may be important in the development of atherosclerotic plaque fracture and subsequent thrombosis or distal embolization. PMID- 2590064 TI - Prednisone increases low density lipoprotein in cynomolgus monkeys fed saturated fat and cholesterol. AB - Cynomolgus monkeys were given prednisone to determine its effects on lipoprotein metabolism and other risk factors for atherosclerotic cardiovascular disease. After 1 month of oral prednisone, the mean total plasma cholesterol (TPC) concentration increased from 240 +/- 36 to 476 +/- 78 mg/dl (p less than 0.01) in animals fed a diet containing 36% of calories as fat (polyunsaturated/monounsaturated/saturated, 1.0:3.9:4.1) and cholesterol (0.39 mg/kcal). The increase in TPC was due to higher concentrations of the apolipoprotein B (apo B)-containing lipoproteins, particularly low density lipoprotein (LDL). LDL cholesterol concentrations also increased in animals fed a diet containing saturated fat and 0.25 mg/kcal of cholesterol, as well as in animals fed monkey chow. Kinetic studies of LDL indicated both an increased flux of apo B into LDL and a decrease in the fractional catabolic rate of LDL. Mean high density lipoprotein cholesterol (HDL-C) concentration decreased from 48 +/- 8.2 to 14 +/- 4 mg/dl, p less than 0.001, in animals fed fat and cholesterol, but there was no significant change in HDL-C in animals fed monkey chow. Blood pressure, fasting serum glucose, and anthropometric measures did not change after 7 months of prednisone therapy. Prednisone increases LDL concentration in the cynomolgus monkey. This animal may be a good model for studying corticosteroid dyslipoproteinemia, and possibly atherosclerosis, in an immunosuppressed host. PMID- 2590065 TI - Plasma lipid secretion and clearance in hyperlipidemic JCR:LA-corpulent rats. AB - The JCR:LA-corpulent rat is an obese, hyperlipidemic, hyperinsulinemic strain that is atherosclerosis-prone and develops myocardial lesions. The hyperlipidemia is due to elevated plasma levels of a large relatively triglyceride-rich very low density lipoprotein (VLDL). Both corpulent and lean male and female rats were studied. Postheparin lipid clearance and apparent hepatic secretion rate after Triton WR1339 inhibition of lipoprotein lipase were determined. The concentrations of cholesterol and cholesteryl esters were not significantly altered by either treatment. Triglycerides showed rapid postheparin clearance in corpulent rats. The apparent hepatic secretion rate was markedly higher in corpulent male rats than in lean male rats, and the rate in corpulent females was again higher, reflecting the higher serum triglyceride concentrations in corpulent female rats. The relative secretion rate of C:48 triglyceride molecular species was lower than that of the C:50 to C:56 species, while the postheparin clearance of C:48 triglyceride molecular species was impaired compared to the C:50 species and those with higher carbon numbers. This effect was more marked in the male than in the female corpulent rats. The results indicate that VLDL hyperlipidemia in the corpulent rat is due to hepatic hypersecretion of VLDL and not to a defect in lipoprotein lipase. Further, the atherogenesis that is characteristic of the corpulent male rat may be related to the differential metabolism of fatty acids. PMID- 2590066 TI - Preservation and structural adaptation of endothelium over experimental foam cell lesions. Quantitative ultrastructural study. AB - To assess the extent to which endothelial cell (EC) structure is modified by hyperlipidemia and by the formation of intimal plaques, we undertook a quantitative ultrastructural study of aortic EC of cynomolgus monkeys after 3 or 6 months on an atherogenic diet. We compared EC in lesion-free areas (LFA) with EC overlying focal discrete foam cell accumulations (FDA) or covering multilayered confluent plaques (MCP). There was a 15% increase in cross-sectional lumen surface profile length over FDA or MCP compared to LFA (p less than 0.005) corresponding to the bulging contours of immediately underlying foam cells. There was, however, no increase in the number of EC per unit of surface area (26.2 +/- 4.47 per 10(4) mm2 for LFA and 26.0 +/- 4.22 for FDA) or, on cross-section, per 100 microns length of underlying internal elastic lamina (8.79 +/- 2.42 for LFA, 8.26 +/- 2.01 for MCP). Nor did the number of surrounding cells contacted by each cell over LFA or MCP differ from normolipemic controls (6.56 +/- 0.85 for LFA and 5.58 +/- 0.86 for MCP). Most ECs were markedly attenuated over lesions, and while the extent and complexity of lateral contact regions between adjacent EC was diminished, the number and complexity of basilar projections was greatly increased. These structures extended among the intimal foam cells to insert on the internal elastic lamina or on intimal matrix fibers, resulting in a 2.7-fold increase in the length of the abluminal portion of the EC profile. The perimeter of the transverse EC profiles was thereby increased from 41.4 +/- 2.12 microns in LFA to 82.2 +/- 5.21 microns over MCP (p less than 0.0001). Polarization of EC in the direction of flow diminished as lesions developed. The ratio of length to width, as well as the standard deviation of the ratio, decreased from 3.51 +/- 3.92 in LFA to 2.35 +/- 0.25 over MCP, due mainly to increases in the proportion of the cell perimeter exposed to the lumen. Lesion localization bore no relationship to the orientation of EC in corresponding locations in the normolipemic controls or in LFA immediately adjacent to plaques. Organelles of EC in hyperlipidemic animals showed features suggestive of increased metabolic activity in all regions, and stress filaments were increased in the EC attenuated over lesions. There was no evidence of EC degeneration, necrosis, or sloughing regardless of lesion location, size, or complexity. PMID- 2590067 TI - Initiation of atherosclerotic lesions in cholesterol-fed rabbits. I. Focal increases in arterial LDL concentration precede development of fatty streak lesions. AB - We have reported that arterial low density lipoprotein (LDL) concentrations and degradation rates in normal rabbits are elevated in those aortic sites most susceptible to early atheromatous lesions resulting from cholesterol feeding. Here we asked whether the focal differences in LDL metabolism observed in normolipidemic rabbits are accentuated during the first 16 days of feeding 2% cholesterol and whether such changes occur before accumulation of significant numbers of macrophage foam cells. No lesions were grossly visible after 16 days of cholesterol feeding. Histology indicated that macrophage foam cells were sparse during this interval and were found only in lesion-prone sites at longer feeding times. We used LDL labeled both with 131I (to trace undegraded LDL), and with the intracellularly trapped ligand 125I-tyramine cellobiose (to trace degraded plus undegraded LDL). The most profound change was a marked and focal increase in the concentration of intact LDL within the arterial wall of lesion prone sites. After 16 days of cholesterol feeding when the plasma LDL cholesterol concentration had increased 7.6-fold, the concentration of intact LDL in lesion prone branch sites of the abdominal aorta was increased by 22-fold (from 2.5 to 54 micrograms LDL cholesterol/g). These concentrations were two and 5.7 times, respectively, as great as in the lesion-resistant, nonbranch areas of the abdominal aorta of the same animals. Similar, but less striking, results were found when the lesion-prone aortic arch and intercostal orifices of the thoracic aorta were compared with adjacent lesion-resistant sites. Arterial LDL degradation rates expressed in terms of LDL mass also increased with time of cholesterol feeding, and were greater in the aortic arch and in branch sites of the abdominal aorta than in adjacent lesion-resistant sites. However, fractional rates of degradation of arterial LDL were decreased in all sites by cholesterol feeding, and were lower in susceptible than in resistant sites. This was probably due in large part to saturation and down-regulation of LDL receptors. The timing, focal nature, and site-specificity of these changes suggest that an increased concentration of LDL in the arterial wall may be an early indication of lesion formation and, in fact, may be a necessary first step in the pathogenesis of the fatty streak lesion in cholesterol-fed rabbits. PMID- 2590068 TI - Initiation of atherosclerotic lesions in cholesterol-fed rabbits. II. Selective retention of LDL vs. selective increases in LDL permeability in susceptible sites of arteries. AB - We asked if the arterial sites most prone to early lesions in cholesterol-fed rabbits have higher permeabilities to low density lipoprotein (LDL) in normolipidemic rabbits or if these sites become more permeable shortly after the onset of cholesterol feeding. We also considered whether the focal increases in the concentration of LDL within the arterial wall in lesion-susceptible sites before fatty streak formation can be explained by increased arterial permeability to LDL or by other mechanisms such as decreased rates of LDL efflux or degradation. 125I-tyramine cellobiose-labeled LDL was injected 1 hour before death to determine the initial rate of LDL entry into lesion-prone and lesion resistant sites of aorta as a measure of permeability. This was studied in normal rabbits and in rabbits fed cholesterol for 4, 8, or 16 days. Combining this permeability data with the tracer data described in the accompanying article, we fit a kinetic model to calculate the mass and mean residence time of intact LDL within the artery and the fractional rates of LDL degradation and efflux from the artery. In normal rabbits, the permeability of lesion-susceptible branch sites of the abdominal aorta was about four times that of the lesion-resistant, nonbranched areas. However, the permeability of the aortic arch, a susceptible site, was similar to that of the lesion-resistant descending thoracic aorta. Permeability to LDL did not increase in any aortic site during the 16 days of cholesterol feeding, even in sites with the largest increases in arterial LDL concentrations. Plasma LDL cholesterol concentration increased substantially and total LDL cholesterol delivery into the artery increased many fold. Since there was no differential change in permeability between susceptible and resistant sites, the increased entry of LDL did not explain the selective increases in arterial LDL concentration in susceptible sites. Kinetic analysis indicated that the fractional rate of degradation of the arterial LDL pool was lower in lesion prone sites than in lesion-resistant sites in all animals. Fractional rates of efflux of arterial LDL decreased in lesion-susceptible branch sites of the abdominal aorta and were low in the lesion-susceptible aortic arch. These results suggest that the focal increases in LDL concentration observed in all lesion susceptible sites of cholesterol-fed rabbits before fatty streak formation are due to localized differences in LDL retention and diminished fractional rates of LDL degradation, not to selectively increased permeability.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2590070 TI - Prescribed drugs--keeping in touch. PMID- 2590071 TI - Senate Committee endorses higher standards for general practice. PMID- 2590069 TI - Effect of dietary fat saturation and cholesterol on low density lipoprotein degradation by mononuclear cells of Cebus monkeys. AB - The mechanism by which dietary unsaturated fatty acids lower low density lipoprotein (LDL) cholesterol is unknown. Unsaturated fatty acids incorporated into the cell membrane can increase membrane fluidity and, as a result, dramatically alter membrane-dependent cell functions. Therefore, we examined the effect of long-term dietary consumption of corn oil and coconut oil with and without cholesterol in amounts equivalent to those of a typical Western diet on the degradation of human LDL by peripheral blood mononuclear cells in Cebus albifrons monkeys. Cellular LDL degradation was dramatically enhanced in the mononuclear cells isolated from animals fed corn oil in comparison with those from animals fed coconut oil. The addition of cholesterol to the diets resulted in a slight attenuation of LDL degradation in the corn oil group while no effect was noted in the coconut oil group. Crossover LDL binding and degradation experiments with LDL isolated from animals fed corn oil diets and coconut oil diets demonstrated increased binding and degradation of LDL in mononuclear cells from animals fed corn oil diets. Enhanced mononuclear cell LDL degradation was accompanied by increased cellular cis-unsaturated fatty acyl content, increased membrane fluidity, and decreased plasma cholesterol. Increased cellular cis unsaturated fatty acyl content with its concomitant increase in membrane fluidity mirrored the dietary lipid profile of the host animal. A linear relationship was observed between cellular LDL degradation and both cellular cis-unsaturated fatty acyl content and membrane fluidity. These observations parallel results noted in whole-animal LDL catabolic studies with these same animals described elsewhere. These data suggest a novel mechanism by which dietary unsaturated fatty acids exert their LDL-lowering effect. PMID- 2590072 TI - Interpractice visits by colleagues. A future option for quality assurance? PMID- 2590073 TI - The rural registrar scheme, 1989. A 12 week pilot study. PMID- 2590074 TI - Treatment of hyperlipidaemias. Current avenues and new horizons. AB - There is now conclusive evidence that lowering cholesterol reduces heart disease. This article describes the use of current lipid lowering drugs and the new HMG CoA reductase inhibitors and fibrates. PMID- 2590075 TI - The penicillins. AB - The penicillins are among the most useful antibiotics despite the increasing problem of bacterial resistance. The authors review the various penicillins available in Australia and emphasise the rationale for their use and the mechanisms of bacterial resistance to these agents. PMID- 2590076 TI - Treatment of supraventricular tachyarrhythmias. AB - The supraventricular tachyarrhythmias (SVT) encompass a variety of rhythm disturbances in which the rate exceeds 100 beats per minute (in adults). Such disturbances originate from sinus, atrial, or atrio-ventricular junctional pacemakers located above the bundle of histidine (His). The treatment depends on the type of arrhythmia, its mechanism and the clinical situation or consequences. PMID- 2590077 TI - Post marketing surveillance of new drugs. Patient safety in the hands of GPs. AB - Is the post market surveillance--the monitoring for safety and tolerability of new drugs--reliable? Will it become compulsory? How does it compare with current detection methods? How reliable are promotional claims drawn from it? This review is a guide to the present, and the implications for the future for general practice. PMID- 2590079 TI - Reference points in the lumbar spine. PMID- 2590078 TI - Patient education using a spreadsheet. AB - Many general practices use a computer, but it can be used for more than accounts and medical records. Preparation of patient information documents is another ideal application. The author shows how a spreadsheet programme can be used to do this showing the cost of smoking both in dollars and loss of life expectancy. PMID- 2590080 TI - Are you master or servant of the telephone? AB - With good organisation, the telephone is a very useful tool in general practice, but if not controlled, it can become master rather than servant. Involvement in its use in your practice is important. PMID- 2590081 TI - Patient education. Heart failure. PMID- 2590082 TI - The use of dithranol. PMID- 2590083 TI - The rarity--an acceptable stimulant. AB - Patients who present with uncommon or unusual or, occasionally, rare complaints help keep doctors vigilant. Such patients can stir the brain to action and prompt stimulating discussions with colleagues. PMID- 2590084 TI - Blindness in the painless white eye. PMID- 2590085 TI - The more things change. PMID- 2590086 TI - Nursing education targets 1989-2000. PMID- 2590087 TI - I'm an individual too. PMID- 2590088 TI - Amphotericin B--antifungal agent. PMID- 2590089 TI - Nurse and the law. Expert evidence. PMID- 2590090 TI - Ventilatory responses to hypoxia and hypercapnia in asthmatics with previous respiratory failure. AB - The ventilatory response to hypoxia and the ventilatory and mouth occlusion pressure response to hypercapnia was measured in 13 subjects who had previously developed respiratory failure or respiratory arrest during an acute asthma attack. In 11 of 12 subjects tested there was a normal response to hypercapnia. Six of the 13 subjects had an impaired response to hypoxia. Impaired hypoxic responsiveness may contribute to the early onset of hypercapnic respiratory failure during acute severe asthma. PMID- 2590092 TI - Regional cerebral blood flow measurements in the diagnosis of dementia. AB - The Xenon-133 regional cerebral blood flow technique (rCBF) was used to assess cortical perfusion in a group of 15 elderly patients (mean age = 79.1, SD = 8.7) with a probable diagnosis of Dementia of the Alzheimer type (DAT). Nine had mild DAT and six were in the moderate stages of DAT. These patients were compared with 15 age and sex matched normal elderly controls (mean age = 75.1, SD = 5.6). RCBF was measured in each patient and control at rest with eyes closed. The DAT patients had significantly lower mean global CBF than normal controls (t = -4.63, p less than 0.0001). In addition, a further 15 normal elderly subjects aged 60 to 92 were assessed and combined with the original 15 to allow calculation of a normal range of rCBF for elderly individuals. Seventy-three per cent of the DAT patients fell below the lower limit of the normal range (39.3 - 59.3 ISI units). These results show the possible usefulness of rCBF as an aid in the diagnosis of early DAT. PMID- 2590091 TI - Long term efficacy of transvenous catheter ablation of the atrioventricular junction for refractory supraventricular tachycardia. AB - Twenty-four patients who underwent transvenous catheter ablation of the atrioventricular (A-V) junction between November 1982 and February 1987 were followed from 18-72 months (mean 47.9) to assess the long term efficacy and safety of the procedure. All had severely symptomatic supraventricular tachyarrhythmias refractory to standard treatment. Atrioventricular conduction was abolished in 23 patients, 22 having permanent pacemakers implanted. Conduction has recovered, though it is modified, in one patient who is asymptomatic on digoxin. Four patients have died; one suddenly 20 months following the procedure, one of progressive heart and liver failure due to hemochromatosis, and two of a stroke. Four patients have had complications related to permanent pacing; one patient has required generator replacement and one patient ventricular lead replacement, one patient had asystole and one patient had a pacemaker-related tachycardia. Two patients remain symptomatic but improved by the procedure. Seventeen patients are free of their original symptoms, 11 having no intervening morbid events. These results demonstrate that patients with severely symptomatic supraventricular tachyarrhythmias may gain long term symptomatic relief from the procedure, but permanent pacing is a cause of significant morbidity and there is a small incidence of late sudden cardiac death. PMID- 2590094 TI - Left ventricular volumes in moderate alcohol users: a study from the workplace. AB - We measured resting and exercise left ventricular volumes by a count-based, nongeometric radionuclide method in 23 healthy volunteers grouped according to reported average daily alcohol consumption: 0-20 g (Gp A), 21-50 g (Gp B) and greater than 50 g (Gp C). No patient had measurable alcohol in his blood at the time of study. Mean resting LV Ejection Fraction (EF) was 65 +/- 2% in Group A, 64 +/- 2% in Group B, and 65 +/- 3% in Group C. Exercise EF was 76 +/- 1,75 +/- 3 and 74 +/- 4%, respectively. Resting Endsystolic Volume Indices in the three groups were 19.2 +/- 3, 18.9 +/- 2 and 21.8 +/- 3 ml/m2; exercise values were 15.9 +/- 2, 12.8 +/- 2 and 13.3 +/- 2 ml/m2, respectively. This cohort was selected for absence of markers of alcohol-related illness, and all subjects were employed. We found no evidence for impaired left ventricular systolic function with moderate alcohol usage using a sensitive radionuclide technique. PMID- 2590093 TI - Detection of rearrangement within the breakpoint cluster region of chromosome 22 in the diagnosis of chronic myeloid leukemia. AB - Chronic myeloid leukemia (CML) is characterised by the presence of a Philadelphia (Ph) chromosome in approximately 95% of patients. Molecular analysis has shown that the Ph chromosome translocation breakpoints are clustered within 5.8 kb on chromosome 22 (breakpoint cluster region or bcr). This has facilitated the diagnosis of CML by nucleic acid hybridisation using probes specific for the bcr to detect DNA rearrangement in this region. Forty patients diagnosed with CML, including four with variant Ph chromosome translocations and three with normal karyotypes were analysed for rearrangement within the bcr. All except one patient with Ph negative CML had rearrangement within the bcr. In contrast, none of the patients diagnosed with other hematological disorders such as the myelodysplastic or myeloproliferative syndromes (16 patients), acute myeloid leukemia (AML) (six patients), acute lymphoblastic leukemia (ALL) (five patients), including Ph positive ALL (two patients), showed rearrangement within the bcr. Analysis for rearrangement within the bcr is useful in the diagnosis of CML, especially when cytogenetic analysis is unsuccessful or in patients with normal karyotypes or variant Ph chromosome translocations. PMID- 2590095 TI - Early and late results of balloon valvuloplasty for severe aortic stenosis. AB - Balloon aortic valvuloplasty has been used as treatment for selected patients with severe aortic stenosis. We report our experience of 11 procedures, performed on ten patients between October 1987 and June 1988. The peak aortic systolic gradient was reduced by 53% from 77 +/- 22 to 37 +/- 14 mmHg (p less than 0.0001) whilst cardiac output did not change significantly (4.1 +/- 1.7 to 3.8 +/- 1.6 (p less than 0.0001) whilst cardiac output did not change significantly (4.1 +/- 1.7 to 3.8 +/- 1.6 L/min). Aortic valve area was increased by 50%, from 0.4 +/- 0.2 to 0.6 +/- 0.2 cm2 (p less than 0.0001). Initial symptomatic improvement was achieved in eight patients. Echocardiographically demonstrated aortic regurgitation did not increase after valvuloplasty. There were no deaths during the procedure, no embolic events and no femoral artery complications. The mean follow-up for survivors was 9 +/- 3 months. Five patients died and three had symptom recurrence at an average of 13 weeks (six-24 weeks). Only two patients reported a continued improvement in symptoms. Balloon aortic valvuloplasty produced a small increase in aortic valve area and a satisfactory initial clinical response, but there was a high incidence of symptom recurrence. The procedure may have a role in the short-term palliation of severely symptomatic patients who are unable to have aortic valve replacement. PMID- 2590096 TI - Chronic strongyloidiasis in Tasmanian veterans--clinical diagnosis by the use of a screening index. AB - Chronic infection with Strongyloides stercoralis presents a diagnostic problem because of the low recovery of the organism from stools and the insensitivity of current serological tests. Of 150 former Far East POWs, 26 (17%) had S. stercoralis in stools. The clinical features in 18 stool-positive patients were compared to those in 24 stool-negative patients and showed that strongyloidiasis was associated with a higher frequency of alteration in bowel habit, upper abdominal discomfort, rash and eosinophilia. On the basis of these features, a screening index was devised which largely separated stool-positive and stool negative patients and led to helpful therapy in three of four patients with compatible symptoms who lacked a definitive diagnosis. Treatment with thiabendazole appeared to be superior to treatment with mebendazole. PMID- 2590097 TI - Bronchopulmonary amyloidosis--multiple tissue involvement and long follow-up. AB - A 59-year-old man developed a large asymptomatic left hilar mass due to amyloidosis of bronchial lymph nodes. Nodular involvement of the left lung and infiltration of the mucosa of the left lower lobe bronchus followed very gradually and a monoclonal gammopathy (IgA--Type Kappa) was demonstrated. Despite slowly progressive radiologic changes, the disease has had no effect on his health during a 20-year period of observation. PMID- 2590099 TI - Connective tissue disease mimicking multiple sclerosis. AB - Systemic lupus erythematosus, primary Sjogren's syndrome and systemic sclerosis may be associated with acute transverse myelitis and chronic relapsing neurological syndromes mimicking multiple sclerosis in the same individuals and/or their relatives. We now present three cases which suggest that there is a wide spectrum of connective tissue disorders mimicking multiple sclerosis and acute disseminated encephalomyelitis. These cases demonstrate that the diagnosis of multiple sclerosis should be kept under constant review by searching for the development of connective tissue disorders in the patients or their relatives. PMID- 2590098 TI - Angiographically demonstrated arterial spasm in a case of benign sexual headache and benign exertional headache. AB - Benign headaches related to sexual activity and exertion are being recognised with increasing frequency. We wish to report a case of benign sexual headache (Type 2) and benign exertional headache, occurring sequentially in the same patient. Multiple areas of cerebral arterial spasm were demonstrable on angiography. This observation would support the concept that benign sexual headache (Type 2) and benign exertional headache may have a similar pathophysiology. PMID- 2590100 TI - Proteinuria, glomerulomegaly and focal glomerulosclerosis in a grossly obese man with obstructive sleep apnea syndrome. AB - A grossly obese (149 kg) man with the sleep apnea syndrome was found to have proteinuria and a supernormal glomerular filtration rate. Renal histology showed glomerulomegaly and focal glomerulosclerosis. It is suggested that obesity may induce glomerular hyperfiltration and in turn glomerulosclerosis. PMID- 2590101 TI - Clinical manifestations of the thrombocytopenia and absent radii (TAR) syndrome. AB - Six patients with the classical features of the TAR syndrome were diagnosed at birth. In one case an older sibling was also affected. The characteristic features of foreshortened forearms and radially deviated hands were noted in all cases at presentation and confirmed radiologically. With one exception skeletal abnormalities of the lower limbs were also present. Varying degrees of thrombocytopenia were present at birth with three of the five patients having platelet counts below 50 x 10(9)/L. Bone marrow examination was performed in two patients and revealed an absence of normal megakaryocytes. Two patients with severe thrombocytopenia had bleeding complications during infancy requiring transfusion support. Severe gastroenteritis occurred in two patients, in one of whom it was attributed to cow's milk intolerance. In all patients the platelet count has risen progressively since birth. Orthopedic surgical procedures have been performed without hemorrhagic complications. PMID- 2590102 TI - Acute necrotising myopathy associated with amiodarone therapy. AB - We report a patient who developed an acute painful proximal myopathy associated with the use of amiodarone. The temporal course, the presence of amiodarone related hypothyroidism and neuropathy, as well as the patient's improvement on drug withdrawal were consistent with a drug reaction. Muscle biopsy demonstrated an acute necrotising myopathy. The mechanism for this reaction is unclear. PMID- 2590104 TI - Methotrexate in rheumatoid arthritis. PMID- 2590105 TI - Pulmonary embolism following placement of a Greenfield Filter. PMID- 2590103 TI - Hypoxic cardiomyopathy: acute myocardial dysfunction after severe hypoxia. AB - Five cases of acute transient myocardial dysfunction in previously well people after severe hypoxic episode are described. In all cases the hypoxic episode was associated with drug overdose and its complications. Pulmonary infiltrates on chest X-ray consistent with pulmonary edema developed in four cases and gated heart pool scanning confirmed severe cardiovascular dysfunction in all cases. PMID- 2590106 TI - Iodothyronine autoantibodies in two sisters. PMID- 2590107 TI - Relatively few clinicians in medical research in Australia: a problem? PMID- 2590108 TI - Zidovudine therapy in HIV-related thrombocytopenia. PMID- 2590110 TI - Cigarette advertising: a matter for paediatric concern. PMID- 2590109 TI - Haemophilus influenzae type b vaccines in Australia? PMID- 2590111 TI - What is the role of paediatric ECMO in Australia? PMID- 2590112 TI - Evaluation of a children's hospital medical peer review programme. AB - The records of medical peer review meetings at the Royal Children's Hospital, Melbourne, were audited for the period 1983-87. This investigation focused on the peer review process, but also evaluated the extent to which recommended changes in medical practice were carried out. The results showed that few recommendations arose from the meetings despite the clear recognition of a number of problem areas. In the instances where firm recommendations were made, few appeared to have been implemented. The main reasons for this failure were: (i) the review was not an integrated part of the medical management structure of the hospital; (ii) recommendations were frequently not made despite clear expressions of the need for action; (iii) the absence of a designated individual to ensure that recommended actions were implemented, together with the lack of a feedback or internal review process to monitor effectiveness; and (iv) a relatively low profile of the peer review. Despite these shortcomings, the peer review is widely perceived to be a valuable exercise, especially as a general educational tool. However, its potential is far greater, and a model is proposed for a more effective medical peer review programme. PMID- 2590113 TI - Arousal deficit: mechanism of the sudden infant death syndrome? AB - Polygraphic tracings of 13 normal infants were recorded in a morning sleep at 1 and 2 weeks of age and 1, 2, 3, 4, and 6 months of age. A vibrotactile stimulus graded at 25, 50 and 100 Hz (frequency) and amplitudes of 1, 2 and 3 mm (intensity) was used, each combination being applied twice at 30 s intervals to the hand of the sleeping infant during active sleep (AS) and quiet sleep (QS). The results were analysed as percentages of failure to arouse (FTA) in relation to the number of stimulus trials, the criteria for FTA being the absence of a response in heart or respiratory rate, electroencephalogram, or chin electromyogram. The percentages of FTA from QS did not change significantly from 1 week to 6 months of age, irrespective of frequency or intensity. The percentages of FTA from AS fell sharply and significantly from 1 week to 2 months of age (P less than 0.001). At 3 months of age there was a significant increase followed by a significant decrease at 4 months of age, both changes showing a significant difference at P less than 0.05. Apart from the first week of age, the numbers of FTA from QS were greater than from AS for all stimulus trials. It is concluded that there is an arousal deficit in QS from 1 week to 6 months of age and the temporary deficit in AS at 3 months of age could explain the peak incidence of SIDS at this time. PMID- 2590114 TI - Child care practices and the sudden infant death syndrome. AB - Southern New Zealand has one of the highest reported rates of the sudden infant death syndrome (SIDS) in the world. Data were collected on 49 infants who died from SIDS in the Dunedin and Invercargill Health Districts of southern New Zealand. Forty-two of the families were interviewed at home following the loss of their infant. In the week prior to death, 17 infants (40%) had an upper respiratory tract infection, although in 11 of these infants their infection had apparently resolved at least 24 h prior to death. Thirty infants (71%) had their faces down into the bedding or their heads covered with bedding. Thirty-four infants (81%) were found dead in the prone position, whereas 49% of New Zealand infants aged 3 months would be expected to sleep prone. Sleep position and the terminal position of the head in relation to SIDS requires further study. PMID- 2590115 TI - Audit of drug usage in a regional neonatal intensive care unit. AB - Drug utilization has been audited prospectively for all infants cared for in a regional neonatal intensive care unit for a 3-month period. Twenty-five infants had a birthweight less than 1500 g and 54 had a birthweight greater than 1500 g. The total number of different drugs used was 76 and the mean number received was 8.6 with a range of 0-30. Infants with birthweights less than 1500 g received a mean of 14.5 drugs and infants with birthweights greater than 1500 g received a mean of 4.8 drugs. Almost two-thirds (63%) of doses were given orally, 20% intravenously and 10% via an umbilical artery catheter. Three drugs, one of which was received by 13% of infants, carried manufacturers' inserts advising against use in premature infants or the newborn. PMID- 2590116 TI - Pneumographic studies: predictors of future apnoeas but not sudden infant death in asymptomatic infants. AB - Pneumograms were performed on 401 asymptomatic infants: 322 siblings, 15 cousins and 24 twins of sudden infant death syndrome (SIDS) victims; 14 siblings of near miss SIDS victims, and 26 infants of anxious parents. The infants of anxious parents had significantly fewer abnormalities than siblings of SIDS victims. In 222 infants subsequently monitored at home, the pneumogram as a predictor of future apnoea had a sensitivity rate of 97.5% and a specificity rate of 72% (P less than 0.001). Infants who were to experience future apnoeas had a significantly higher percentage of time in periodic breathing and a higher density of apnoeas in their original pneumograms. However, the abnormal pneumogram did not predict SIDS, because the eight infants who died all had normal pneumograms. PMID- 2590117 TI - Early identification of cerebral palsy in high risk infants. AB - This study of high risk infants aimed to identify which signs at the corrected ages of 1, 4 and 8 months were important for distinguishing those infants who later developed hypertonic cerebral palsy (CP). From a total cohort of 450 infants (350 of birthweight less than 1500 g and 100 of birthweight greater than 1500 g), 26 infants were later diagnosed as having CP and formed the study group. A control group of 26 infants from the same initial cohort who did not develop CP was matched to the study group. Both groups were followed for a minimum of 2 years. At each assessment (1, 4, 8, 24 months corrected age), all children were assessed using a standard medical examination and a detailed neurosensorimotor developmental scale that evaluated neurological signs, motor attainments, primitive reflexes and postural reactions. Each test response was graded as normal, suspect or abnormal and the results for the two groups were compared. Assessment at 1 month failed to identify a number of the CP infants whereas at 4 months there was some overidentification. At 8 months, assessment was highly predictive of cerebral palsy. Individual signs of abnormality were found to be of limited value but the presence of three or more abnormal signs at 8 months was highly predictive of CP. PMID- 2590118 TI - Early childhood development: a comparative study of beliefs held by adolescents, medical students and mothers. AB - This study examined beliefs about the normal development of preschool children held by adolescents, medical students and mothers. A consistent pattern was identified, with adolescents estimating that young children can do the least, medical students' estimations lying between those of adolescents and mothers, and mothers estimating that the children can do the most. In addition, medical students were found to change their beliefs during the time that they participated in their paediatric teaching programme. It is suggested that paediatricians and other child health professionals take into account the varying beliefs held by different groups in the community when providing advice or teaching about early child development. PMID- 2590119 TI - Hospital admissions for infections of aboriginal and non-aboriginal infants and children in Western Australia, 1981-86. AB - Rates of hospital admissions and bed usage for infections by Aborigines up to 15 years of age were much higher in Western Australia during 1981-86 than they were for the rest of the population. These rates for Aboriginal infants for gastroenteritis, for example, were 20-25 times and 40-50 times those for other infants. The rates mostly declined over the 6 years except for gastrointestinal and respiratory infections in Aboriginal infants and young children in rural and remote areas. Hospitalization rates reflect many factors which include disease incidence and severity but also distance, climate and access to medical and nursing care and their utilization. Preventative health programmes must be maintained to help improve the health of young Aborigines. PMID- 2590120 TI - Carbohydrate metabolism on high dose growth hormone therapy in children treated for leukaemia. AB - The effect on carbohydrate metabolism of a high dose growth hormone (GH) regimen (1.2 U/kg per week) was assessed on 24 children who had previously been treated for leukaemia. Sixteen patients received high dose GH and eight patients received a conventional dose of GH (0.6 U/kg per week). Oral glucose tolerance tests (OGTT) were performed at baseline and after 3 months of treatment with GH. For the entire group between 0 and 3 months, there was a significant increase in mean (and standard deviation) fasting plasma glucose (0.3 +/- 0.6 mmol/L), fasting insulin level (11 +/- 26 mU/L), and 2 h insulin level (20 +/- 40 mU/L). One patient, who received a conventional dose of GH, developed substantial carbohydrate intolerance. For the entire group, there was no change in response to a carbohydrate load at 3 months as measured by the area under the plasma glucose or insulin curve. There was no significant difference between conventional and high dose groups at 3 months as assessed by these parameters. This study demonstrates that a higher dose of GH may be used in these children in an attempt to improve their final height, without increased risk of carbohydrate intolerance in the short term. PMID- 2590121 TI - Nephrotic syndrome in Kawasaki disease. AB - Renal manifestations in Kawasaki disease are rare, and nephrotic syndrome in this disorder has not been described previously. We report a 3 month old infant with Kawasaki disease, presenting with nephrotic syndrome which responded to steroid therapy. The patient, however, developed coronary aneurysms and died of acute myocardial infarction. PMID- 2590122 TI - Rendu-Osler-Weber syndrome in a 9 year old girl presenting with repeated haemoptysis. AB - A case is reported of Rendu-Osler-Weber syndrome presenting in a 9 year old girl as recurrent haemoptysis. Despite a normal chest X-ray, the patient was found to have multiple areas of angiodysplasia in the major airways of her right lung. PMID- 2590123 TI - Coarctation of the aorta and lower limb blood pressure. PMID- 2590124 TI - Stabilization and fixation of percutaneous central venous catheters. PMID- 2590125 TI - Adolescent suicide. PMID- 2590126 TI - Deaths from asthma. PMID- 2590127 TI - Process evaluation of the bassinet restraint loan scheme in Victoria. AB - The value of the use of safety restraints for all vehicle occupants has been recognized, and corresponding legislation has been implemented in Australia. However, legislation alone has not been sufficient to increase significantly the use of safety restraints for infants. In an attempt to address this issue, a statewide infant safety restraint loan scheme has been in operation in Victoria since May 1985. At the time of this study, 203 of 210 municipalities in Victoria were participating in the scheme. An operational evaluation of the Bassinet Loan Scheme (BLS) was undertaken after 18 months of operation. Questionnaires were completed by 426 parents attending selected maternal and child health centres. The questionnaire was designed to provide information about the use of safety restraint for infants aged 0-6 months, parental attitudes towards the restraint, and sociodemographic characteristics. The study demonstrated that 81% of the population surveyed used the infant safety restraint, but only 52% were in the BLS. The pattern of usage of safety restraints for infants was related to maternal age and educational level. PMID- 2590128 TI - Fifth day fits in the newborn. AB - During the 1970s, there was an epidemic of neonatal convulsions occurring in apparently normal babies during the fourth and fifth days of life. This syndrome was noted in France as well as in Australia. A study was undertaken to review the King George V Hospital (KGV) experience with these 'fifth day fitters'. All cases of neonatal convulsions at KGV during the years 1972-85 were reviewed. A total of 94 cases of fifth day fits occurred during this period, accounting for 57% of all neonatal convulsions occurring during 1972-79. The fits occurred in healthy term infants after an uncomplicated pregnancy. They appeared on the fourth and fifth days of life. The seizures lasted an average of 24 h, were refractory to drug therapy and, despite extensive investigation, no cause was found. The infants were assessed as normal at the time of discharge from hospital. Follow-up of these infants was incomplete. However, from the data available, it cannot be assumed to be a benign entity. The 'fifth day fit' syndrome reached epidemic proportions at a number of maternity units during the 1970s. At KGV, no case has been observed since 1982. PMID- 2590129 TI - Selective improvement in cognitive test scores of extremely low birthweight infants aged between 2 and 5 years. AB - The cognitive development at 2 and 5 years of a cohort of extremely low birthweight (ELBW) children (birthweight 500-999 g) was compared with that of cohorts of larger very low birthweight (VLBW) children (birthweight 1000-1500 g) and normal birthweight (NBW) children (birthweight greater than 2500 g) to determine whether the improvements in cognitive function of ELBW infants between 2 and 5 years are apparent or real. At 2 years of age, ELBW children had a mean Mental Developmental Index (MDI) on the Bayley Scales of 90.4, significantly lower than the means of 100.3 for the larger VLBW children (P = 0.006), and 107.8 for the NBW children (P = 0.0002). However by 5 years the mean scores on the Wechsler Preschool and Primary Scales of Intelligence (WPPSI) full-scale for the ELBW and larger VLBW children were virtually identical (105.9 and 106.0 respectively)--but still lower than the mean WPPSI full-scale of 114.6 for the NBW children. After standardizing the MDI and WPPSI scores relative to the NBW children, the ELBW children improved between 2 and 5 years (paired t-test, t = 3.2, P = 0.004) whereas the larger VLBW infants did not. We postulate that ELBW children require more time than larger VLBW children after birth to compensate for perinatal and other stresses, and that developmental delay at 2 years may not always persist to 5 years. PMID- 2590130 TI - Deletion analysis for Duchenne (and Becker) muscular dystrophy. AB - Forty-three unrelated South Australian boys diagnosed as having either Duchenne or Becker muscular dystrophy were screened for deletions using DNA probes to the dystrophin gene. For the 35 boys with Duchenne muscular dystrophy, the deletion frequency was 43% using a simplified probing strategy based on the probes Cf56a, Cf56b, pERT87-15 and XJ (XJ1.1 or XJ2.3). The corresponding deletion frequency for the eight boys with Becker muscular dystrophy was 38%. Members of families in which these disorders result from a deletion can now choose to prevent the birth of further affected boys, using an accurate prenatal test for the specific mutation occurring within the family. Deletion analysis also has the potential to clarify the carrier status of women in these families. PMID- 2590132 TI - Gastric retention of a swallowed coin after surgical treatment of pyloric stenosis. AB - In patients with a past history of pyloric stenosis, swallowed foreign bodies may not pass out of the stomach. Not only is this clinically relevant, but it also suggests that, even after apparently successful surgery, pyloric function may not be completely normal. A case history is presented and the literature is reviewed. PMID- 2590131 TI - Noonan syndrome with spontaneous chylothorax at birth. AB - A female Chinese infant having the features of Noonan syndrome presented with acute respiratory distress at birth, secondary to a large spontaneous left-sided chylothorax. This condition must be recognized early in such infants, as prompt thoracentesis is life-saving. PMID- 2590133 TI - A cautionary note regarding the ACP policy statement on alcohol consumption in relation to pregnancy. PMID- 2590134 TI - Breast feeding and HIV infection. PMID- 2590135 TI - The Australian College of Paediatrics and the Paediatric Research Society of Australia. Abstracts of papers presented at the annual scientific meeting. May 1989. PMID- 2590137 TI - Inhibited development of trichostrongylid worms in grazing cattle. AB - Inhibition of development of gastro-intestinal trichostrongylid worms was studied using successive groups of tracer calves and groups of continuously grazed calves over one year in the Tully area of North Queensland lowland wet tropics. The results, assessed by means of worms from these calves recovered at necropsy 3 weeks after their removal from pastures, showed inhibition in the development of Haemonchus placei and Cooperia punctata at the early fourth stage at the approach to and during the relatively dry period in the area. Inhibition was however minor and inhibited larvae formed but only a small percentage of worm burdens in both categories of calves, indicating that they were not in any way of major epidemiological importance. It was suggested that the minor nature of inhibition was due to the mild climatic conditions which could not produce appropriate conditioning treatment, or caused only mild selection pressure for inhibition in the area. PMID- 2590136 TI - Detecting benzimidazole resistance with faecal egg count reduction tests and in vitro assays. AB - Composite strains of Trichostrongylus colubriformis and Ostertagia spp consisting of 0, 1, 10, 25, 50, 75, 90, and 100% of known resistant strains were prepared and tested for benzimidazole resistance using faecal egg count reduction tests, in vitro egg hatch assays and tubulin binding assays. All tests detected resistance where the proportion of the resistant strain in the composite was 50% or more, whereas none of the tests unequivocally detected resistance below 25%. Egg count reduction tests were no less sensitive than the in vitro tests in detecting low levels of resistance but the egg hatch and tubulin binding assays provided a better quantitative estimate of moderate to high levels of resistance. Faecal egg count reduction therefore, provides a suitable means of detecting resistance in the field but tests, more sensitive to low levels of resistance are required. Results indicate that the use of post-treatment counts alone provides an adequate indication of anthelmintic efficiency. PMID- 2590138 TI - Induction of heat stress in beef cattle by feeding the ergots of Claviceps purpurea. AB - Two groups of 4 Hereford steers were housed in a controlled environment room and exposed to simulated high summer temperatures. Both groups were fed a barley grain and hay diet ad libitum. The barley in one diet contained 0.5% w/w ergots of Claviceps purpurea. Within one week of feeding the ergot diet mean rectal temperature was significantly elevated (P less than 0.05) each afternoon (up to 41 degrees C) but returned to normal overnight. Elevated rectal temperature was accompanied by other signs of heat stress, reduced feed intake, body weight loss and depression or serum prolactin concentration. Symptoms disappeared within 1 week of ceasing to feed the ergot diet. PMID- 2590139 TI - Sex-related responses to vitamin B12 and trace element supplementation in prime lambs. AB - Bodyweight, plasma vitamin B12 and blood selenium concentrations were monitored in prime lambs given different forms of supplementation at 2 sites in separate years. At the first site treatment groups comprised control, vitamin B12 injection, selenium given orally and a combination of vitamin B12 and selenium. At the second site cobalt and selenium supplied in a glass bullet was compared with an untreated group. Significant sex-related responses were observed to treatment in terms of bodyweight and at site 2 in plasma vitamin B12 concentrations. A marked bodyweight response to glass bullet supplementation was observed in castrated male lambs but not in ewe lambs. These studies show that sex differences should be considered when investigating trace element deficiencies. PMID- 2590140 TI - Cor pulmonale in an Angus cow. AB - Cor pulmonale was diagnosed in a 4-year-old beef cow at pasture. Clinical and pathological evidence for the diagnosis included ventral oedema, respiratory distress, chronic interstitial pneumonia and cardiac failure. The cause of the pneumonia was not identified. PMID- 2590141 TI - Fibrosis and contracture of the semitendinosus muscle in a dog. PMID- 2590143 TI - Cannulation of the rumen in cattle and buffaloes. PMID- 2590142 TI - Pathology of reproductive tracts of merino rams in north western Queensland. PMID- 2590144 TI - Use of ethanol for euthanasia of mice. PMID- 2590145 TI - Hyperthermia impairs retrieval of an overtrained spatial task in the Morris water maze. AB - Fifteen rats were trained to learn the location of a spatially fixed platform hidden in a Morris water maze (40 +/- 2 degrees C). Then retention of the spatial task was assessed immediately after raising core body temperature (Tc) to 42 or 40 degrees C or stabilizing at 37 degrees C (the normothermic control). The hyperthermic treatment order was counterbalanced according to a Latin-square design. Hyperthermia at 42 degrees C Tc significantly impaired spatial performance. Hyperthermic animals were cooled to normothermia (Tc = 37 degrees C) and spatial performance was tested again approximately 30 min later. Cooling resulted in a complete recovery of spatial performance. These results demonstrate that hyperthermia-induced amnesia can be obtained on an overtrained spatial mapping strategy and cooling to normothermia initiates recovery of spatial performance. PMID- 2590146 TI - Damage to the hippocampal formation in rats selectively impairs the ability to learn cue relationships. AB - We assessed the contribution of the hippocampal formation to performance in tasks that require rats to respond to a relationship between discriminative stimuli. The first experiment employed a nonmatching-to-sample procedure in a Y-maze. Three pairs of boxes were used which differed in brightness of the walls and in the odors that they contained. The rats were trained prior to receiving kainic acid and colchicine-induced damage to the hippocampal formation or electrolytic damage to the amygdala. After surgery all rats performed the nonmatching-to sample task accurately if both brightness and odor cues were present in the sample and choice boxes or if the boxes contained either visual cues alone or odor cues alone. If the available cue modality was different in sample and choice boxes, then the amygdala-damaged, but not the hippocampal-damaged, rats performed accurately. In the second experiment control rats or rats with hippocampal formation damage were trained postoperatively in a conditional black/white discrimination task in a Y-maze. Only the control group successfully learned to select the white arm if the start box was illuminated and the black arm if the start box was dark. Subsequently, both groups learned a simple black/white discrimination. The same rats were tested in the hidden platform version of the Morris water task and only the control group learned to swim accurately to the goal. Both groups learned to swim accurately to a visible black platform. The results are consistent with the notion that the hippocampal formation is essential to learning that involves control exerted by a configural relationship among cues, independently of the spatial or conditional requirements of tasks. PMID- 2590147 TI - Facilitation of acquisition and retention in preweanling but not postweanling rats by the presence of familiar home-nest material. AB - A series of four experiments examined the effect of the presence of stimuli from the home nest on the acquisition and retention of aversively motivated behaviors in preweanling and adult rats. In Experiment 1, training in the presence of home nest shavings facilitated acquisition of a T-maze discrimination to escape footshock for 16-day-old rats but not for adults. Experiment 2 demonstrated that the extent to which preweanlings were familiar with the home shavings determines the degree to which these stimuli facilitate spatial discrimination learning. When clean shavings were made more familiar than soiled home-nest stimuli (by changing the shavings every day) clean shavings enhanced discrimination performance, whereas no enhancement of learning by home shavings was observed. Experiment 3 extended the generality of the enhancement effect to a conditioned location aversion and examined the extent to which this facilitative effect was due to the tendency for home-nest shavings to elicit approach responses. Expression of the conditioned aversion was enhanced in subjects conditioned in the presence of home shavings, regardless of whether the home shavings were presented with the CS+, the CS-, or both. Experiment 4 determined that the enhanced expression of learning in the context of home-nest stimuli observed for preweanlings did not occur among subjects trained shortly after weaning. Collectively, these data suggest that whereas the enhancement of learning and retention by familiar home-nest stimuli enjoys generality across a number of conditioning situations, the effect may be limited to a relatively brief period during ontogeny. PMID- 2590148 TI - The stability and interest consonance of lateral postural--motor biases in rats: results and implications. AB - Each of six different tests of lateral postural-motor asymmetries was repeatedly administered to 126 rats. Directional reliability was found for rotatory swimming, open-field exploration, and stepping down from a beam. Neonatal posture, turn in an unbaited T maze, and orientation to tail pinch proved not to be reliable across days. The behavioral asymmetries in the open-field and step down tests were directionally consonant with each other, but neither was related to the asymmetry exhibited in rotatory swimming, implying the existence of at least two independent asymmetrical neural substrates underlying the behaviors. Neither sample-wide directional biases nor major sex differences in bias were found. The sexes were, however, differentially influenced in direction on some tests by the number of males in their natal litters, implying a role for intrauterine exposure to androgens in predisposing rats toward some left- or right-biased behaviors. PMID- 2590149 TI - Behavioral bias and left-right response differentiation in the rat. AB - To examine the proposition that lateral asymmetry facilitates left-right response differentiation in rats, we examined the relationships between the strengths of several behavioral biases and the scores on a learning task requiring left-right response differentiation. No support was found for a simple model positing a monotonic relationship between any behavioral bias and the learning scores. However, performance showed a U-shaped relationship to one behavioral bias. This finding conforms to a curvilinear model in which rats at either extreme of asymmetry are disadvantaged, at low degrees of asymmetry by a lack of navigational reference, and at high degrees by resultant strong position habits; moderately asymmetrical rats have neither disadvantage and are best able to use the asymmetry as a reference in processing left-right information. PMID- 2590150 TI - Development of rotorod performance in normal and congenitally hypothyroid mutant mice. AB - Balancing behavior on a rotating cylinder was measured in genetically hypothyroid (hyt/hyt) mutant mice and their phenotypically normal littermates (hyt/+) at 10 different ages between Day 12 and Day 55. Normal mice showed competent balancing behavior in this task by 23 days of age, but mutant hypothyroid mice were incapable of balancing throughout the period of testing. Similar results were found with animals initially tested as adults, indicating that the developmental effects are probably not attributable to different rates of learning. These results are discussed in terms of documented central nervous system abnormalities in animals deprived of thyroid hormone early in life. PMID- 2590151 TI - Independence of uniphasic and biphasic audiogenic seizure progressions in mice. AB - DBA/2J mice were monaurally or binaurally tested for susceptibility to sound induced seizure. Two seconds following the beginning of running, one group of binaurally tested mice had acoustic stimulation interrupted for 15 s. These mice later seized when the stimulation was readministered. Their seizure progression closely resembled the behavior exhibited by noninterrupted binaurally stimulated mice and did not shift to the biphasic motor pattern of monaurally stimulated subjects. We conclude that the single burst of running of a binaurally tested mouse is qualitatively different from either of the two bursts of running exhibited by monaurally tested mice. PMID- 2590152 TI - Effects of atropine injection on food-associated drinking in rats with superior salivatory nucleus lesions. AB - The neuropharmacological mechanisms involved in the prandial drinking pattern seen in rats with superior salivatory nucleus lesions + parotidectomy were investigated with behavioral methods. Results showed that the administration of low doses (0.1 mg/kg body wt) of atropine in lesioned rats potentiated previously established prandial drinking. Higher doses of atropine (1.0 mg/kg), however, were required to induce a similar degree of prandiality in control rats (parotidectomy alone). These findings suggest that the salivatory nucleus lesions affected a cholinergic brainstem-salivary gland system involved in the neural control of food-associated drinking. PMID- 2590153 TI - The development of olfactory preferences for artificial odors briefly experienced by the precocial spiny mouse young. AB - Groups of pups, aged 2, 4, 6, 12, 16, and 18 days of the precocial murid rodent spiny mouse (Acomys cahirinus), were each exposed for 1.5 h to one of the experimental odors, cinnamon or cumin, present in the surrounding environment. The odors were not contingent upon home-cage odors or any other reinforcers. This simple exposure produced a strong preference for the exposed odor in multichoice preference tests carried out 48 h after the exposure in pups from groups aged 2 through 16 days. Older pups exposed to cinnamon or cumin at Day 18 did not show a significant preference for the familiar odor. Both experimental odors used were found to be neutral for control experimentally naive pups within a tested age span. These results point at a stimulus familiarity, rather than associative learning in the development of olfactory preferences in young spiny mouse pups. PMID- 2590154 TI - [The effect of combined antibiotic and immune prophylaxis against atrophic rhinitis on the body weight of swine]. AB - In a natural outbreak of Atrophic Rhinitis, the weaned piglets were divided into four groups. Group 1 (10 weaned piglets); Their mother was vaccinated with 2 ml Rhinipig i. m. 3 weeks prior to farrowing. The piglets received 0.2 ml each of Pargenta 50 (= 10 mg Gentamycin) k. m. on the third, fifth and seventh days after birth. The piglets were fed a food containing 10 ppm Gentamycin base during the 6 weeks following their weaning. Group 2 (10 weaned piglets); Their mother was vaccinated with 2 ml Rhinipig i. m. 3 weeks prior to farrowing. The piglets received 0.2 ml each of Pargenta 50 (= 10 mg Gentamycin) i. m. on the third, fifth and seventh days after birth. Group 3 (10 weaned piglets); Their mother was vaccinated with 2 ml Rhinipig i. m. 3 weeks prior to farrowing. Group 4 (10 weaned piglets, untreated, experimental control group). The results were during the growing period (from 12.3 kg to 32-34.9 kg) and during the finishing period (from 32-34.9 kg to 100 kg) evaluated. Group 1 showed significantly better food conversion and daily weight gain in both periods when compared to the other groups. Although the difference of daily weight gain between Group 1 and Groups 2 and 3 where diminished by 4.34% respectively 1.72%. PMID- 2590155 TI - [Campylobacter infection and Campylobacter excretion in turkeys]. AB - Five turkey poults at an age of 27 days were infected with Campylobacter jejuni strain. Additional five poults were infected by contact. Turkeys infected by contact and artificially were necropsied 1 and 3 months later, respectively. The histological examination of the liver revealed degenerative changes in contact birds and a proliferation of the connective tissue and bile-ducts in two of the oral infected poults. Campylobacter spp. were excreted daily during the first two weeks and afterwards with interruptions of several days. The excretion lasted until the end of the experiment between day 86 and 98. The excretion period, which is prolonged compared with that of chickens may be of particular importance under aspects of epizootiology and food hygiene. PMID- 2590156 TI - [Molecular characterization of the hog cholera virus]. AB - The molecular biology of hog cholera virus (HCV) was studied. After reverse transcription of the viral RNA the cDNA was cloned in the expression vector lambda gt11. HCV clones were identified using antibodies as a probe. Partial sequencing of one HCV-derived cDNA clone revealed a high degree of homology to a portion of the bovine viral diarrhea virus (BVDV). One goal of these studies is the preparation of defined, effective and safe vaccines against pestiviruses. PMID- 2590157 TI - [A case of an undifferentiated rhabdomyosarcoma in a hen]. AB - A more than hen's-egg-sized tumour was found in the breast muscle of a seven months old chicken. In liver, lungs and kidney metastases were seen. The light- and electronmicroscopic survey led to the diagnosis of an undifferentiated rhabdomyosarcoma. PMID- 2590158 TI - [Experimental cesarean sections in the cat]. AB - Results of experimental Cesarean sections in the cat at different stages of gravidity were compared with the recommendations given in the literature. PMID- 2590159 TI - Enzyme kinetics of cellulose hydrolysis. PMID- 2590160 TI - Specificity of ribosome-inactivating proteins with RNA N-glycosidase activity. PMID- 2590161 TI - Defective activity of acyl-CoA:cholesterol O-acyltransferase in Niemann-Pick type C and type D fibroblasts. AB - The activity of acyl-CoA:cholesterol acyltransferase (ACAT; EC 2.3.1.26) was measured in fibroblast homogenates from Niemann-Pick Type C (NPC) and Type D (NPD) patients to determine whether these cells exhibit similar defects in the regulation of cholesterol esterification. ACAT activity in normal cells cultured in the absence of serum lipoproteins responded rapidly (within 6 h) to the addition of serum and reached peak levels at 12-24 h, whereas little stimulation of activity in NPC cells was observed. In contrast, ACAT activity in NPD fibroblasts (cell lines from four different patients) began to increase between 6 and 12 h after serum addition, reaching levels up to 50% of normal values at 24 h. ACAT activity in NPC and NPD cell extracts could not be stimulated by preincubation with normal cell homogenates, nor was complementation between NPC and NPD homogenates observed. Addition of 25-hydroxycholesterol to fibroblasts cultured in delipidated serum increased ACAT activity for all three cell types, although stimulation in NPD cells was less than that observed in NPC cells. ACAT activity of deoxycholate-solubilized homogenates reconstituted into phosphatidylcholine vesicles was independent of the presence of serum lipoproteins during culture and dependent on cholesterol present in the vesicles for all cell types. However, ACAT activities of mutant fibroblasts in vesicles plus cholesterol were significantly (about 40%) lower than control levels. These results suggest that the metabolic lesions in NPC and NPD cells are biochemically distinct and that both may involve factors in addition to the availability of cholesterol substrate for the ACAT enzyme. PMID- 2590162 TI - Protective role of fructose 1,6-bisphosphate during CCl4 hepatotoxicity in rats. AB - Rats were injected intraperitoneally with CCl4 (2.5 ml/kg body wt.) and the hepatotoxicity was compared with that of rats receiving the same dose of CCl4 and an intraperitoneal injection of fructose 1,6-bisphosphate (2 g/kg body wt.). A 50 70% decrease in plasma aspartate aminotransferase and alanine aminotransferase activities was observed in the latter treatment, indicating a protective role of the sugar bisphosphate in CCl4 hepatotoxicity. The protection was accompanied by elevated hepatic activities of ornithine decarboxylase at 2, 6 and 24 h, S adenosylmethionine decarboxylase at 6 h, and spermidine N1-acetyltransferase at 2 h. The increase in the enzymes involved in polyamine metabolism was shown in our previous work [Rao, Young & Mehendale (1989) J. Biochem. Toxicol. 4, 55-63] to correlate with increased polyamine synthesis or interconversion, which was related to the extent of hepatocellular regeneration. The hepatic contents of fructose 1,6-bisphosphate and ATP significantly decreased after CCl4 treatment, and administration of the sugar bisphosphate increased hepatic ATP. Fructose 1,6 bisphosphate, an intermediary metabolite of the glycolytic pathway, may decrease CCl4 toxicity by increasing the ATP in the hepatocytes. The ATP generated is useful for hepatocellular regeneration and tissue repair, events which enable the liver to overcome CCl4 injury. PMID- 2590163 TI - An analysis of myo-[3H]inositol trisphosphates found in myo-[3H]inositol prelabelled avian erythrocytes. AB - Evidence is presented to show that acid extracts of avian erythrocytes prelabelled for 24-48 h with myo-[3H]inositol contain the following myo [3H]inositol trisphosphates (expressed as a percentage of total myo-[3H]inositol trisphosphates extracted): 36% myo-[3H]inositol 1,4,5-trisphosphate; 33.7% myo [3H]inositol 1,3,4-trisphosphate; 13% myo-[3H]inositol 3,4,5-trisphosphate; 9.7% myo-[3H]inositol 3,4,6-trisphosphate; 4.4% myo-[3H]inositol 1,4,6-trisphosphate and 3.3% myo-[3H]inositol 1,3,6-trisphosphate. The only phosphatidyl-myo [3H]inositol bisphosphate that could be detected in [3H]Ins-prelabelled avian erythrocytes was phosphatidyl-myo-[3H]inositol 4,5-bisphosphate. Cellular myo [3H]inositol 3,4,5-trisphosphate may be synthesized by dephosphorylation of myo [3H]inositol 3,4,5,6-tetrakisphosphate. D- and L-myo-[3H]inositol 1,4,6 trisphosphate and D- and L-myo-[3H]inositol 1,3,6-trisphosphate may be dephosphorylation products of myo-[3H]inositol 1,3,4,6-tetrakisphosphate. PMID- 2590164 TI - Structure and evolutionary origin of the gene encoding a human serum mannose binding protein. AB - The N-terminal sequence of the major human serum mannose-binding protein (MBP1) was shown to be identical at all positions determined with the amino acid sequence predicted from a cDNA clone of a human liver MBP mRNA. An oligonucleotide corresponding to part of the sequence of this cDNA clone was used to isolate a cosmid genomic clone containing a homologous gene. The intron/exon structure of this gene was found to closely resemble that of the gene encoding a rat liver MBP (MBP A). The nucleotide sequence of the exons differed in several places from that of the human cDNA clone published by Ezekowitz, Day & Herman [(1988) J. Exp. Med. 167, 1034-1046]. The MBP molecule comprises a signal peptide, a cysteine-rich domain, a collagen-like domain, a 'neck' region and a carbohydrate-binding domain. Each domain is encoded by a separate exon. This genomic organization lends support to the hypothesis that the gene arose during evolution by a process of exon shuffling. Several consensus sequences that may be involved in controlling the expression of human serum MBP have been identified in the promoter region of the gene. The consensus sequences are consistent with the suggestion that this mammalian serum lectin is regulated as an acute-phase protein synthesized by the liver. PMID- 2590165 TI - The intrinsic tryptophan fluorescence of beta 1-bungarotoxin and the Ca2+-binding domains of the toxin as probed with Tb3+ luminescence. AB - beta 1-Bungarotoxin has only one tryptophan residue, namely Trp-19 in the phospholipase A2 subunit. The environment of Trp-19 was studied by intrinsic fluorescence and solute quenching. The native protein showed an emission peak at 330 nm. About 90% of the fluorescent tryptophan was accessible to quenching by either acrylamide or KI but not to CsCl. A red-shift in the emission peak occurred between 2.0 M- and 4.0 M-guanidinium chloride, and the helix-coil transition of the polypeptide backbone occurred between 4.0 M- and 6.0 M guanidinium chloride. These results suggested that Trp-19 was in a less polar medium but near a positive charge. The local conformation around Trp-19 could be disturbed by binding of Tb3+ or Ca2+ or Sr2+ to the toxin molecule. Tb3+ a tervalent lanthanide ion, effectively substituted for Ca2+ in stimulating the phospholipase A2 activity of beta 1-bungarotoxin. Upon the binding of Tb3+ to the toxin, the Tb3+ fluorescence in the 450-650 nm region was enhanced. This resulted from the energy transfer from Trp-19 to Tb3+. The distance between the energy transfer pair was estimated to be 0.376-0.473 nm at pH 7.6 and 0.486-0.609 nm at pH 6.3. Assuming that there were two Tb3+-binding sites on the toxin molecule, at pH 7.6 the association constants of the high-affinity and the low-affinity sites were determined to be 3.82 x 10(3) M-1 and 2.85 x 10(2) M-1 respectively. At between pH 6.0 and 7.0 Tb3+ bound to the high-affinity site decreased greatly but did not disappear entirely. Both Ca2+ and Sr2+ competed with Tb3+ at the high affinity sites, but Sr2+ could not substitute for Ca2+ in stimulating the phospholipase A2 activity. PMID- 2590166 TI - pH-induced bistable dynamic behaviour in the reaction catalysed by glucose-6 phosphate dehydrogenase and conformational hysteresis of the enzyme. AB - 1. Bistable (multiple stationary states) dynamic behaviour in the activity of glucose-6-phosphate dehydrogenase that was subjected to successive pH change was demonstrated in an open continuously stirred tank reactor. Although the enzyme under study did not exhibit an autocatalytic effect and was homogeneously distributed, bistability was shown to occur. 2. The successive pH changes of the enzyme solution corresponded to a pH transition (8.3 in equilibrium 2), i.e. an acidification (forward direction) and an alkalinization (reverse direction). By use of intrinsic protein fluorescence methods, a glucose-6-phosphate dehydrogenase conformational hysteresis was shown to exist concomitant with the pH transition before and after enzyme injection into the reactor. 3. The results obtained suggest that the enzyme behaves, conformationally, as a memory device that stores information about its pH history (i.e. the enzyme records information in its structure about the environment to which it was previously exposed) and transduces it in a non-linear dynamic fashion, producing the bistable behaviour observed in the open reactor. PMID- 2590167 TI - L-carnitine acyltransferase in intact peroxisomes is inhibited by malonyl-CoA. AB - Inhibition of the overt mitochondrial carnitine palmitoyltransferase by malonyl CoA is important in the regulation of fatty acid oxidation. In the past, the contribution of peroxisomal carnitine acyltransferase activity to the generation of medium- and long-chain acylcarnitines in the cytoplasm has been ignored. On the basis of marker enzyme levels, we now estimate that peroxisomal palmitoyltransferase activity constitutes about 20% of the peroxisomal plus overt mitochondrial pool in fed rat liver. When assayed in situ, both the palmitoyltransferase and decanoyltransferase activities of gradient-purified peroxisomes are sensitive to malonyl-CoA, with up to 90% inhibition reached at less than 10 microM-malonyl-CoA. Very similar results were obtained with intact gradient-purified mitochondria from the same livers. In addition, the acyl-CoA substrate chain-length specificity was identical in both the peroxisomes and the mitochondria, with a decanoyltransferase/palmitoyltransferase ratio of 2. Thus the overt carnitine acyltransferase activities in peroxisomes and mitochondria have the same properties. Further, the malonyl-CoA sensitivity of the peroxisomal activity is lost on solubilization, as has been observed for the overt mitochondrial enzyme. It is suggested that malonyl-CoA inhibition of the peroxisomal enzyme as well as of the mitochondrial enzyme is important for the regulation of mitochondrial fatty acid oxidation. PMID- 2590168 TI - Regulation of production of delta-aminolaevulinate synthase in tissues of chick embryos. Effects of porphyrogenic agents and of haem precursors. AB - Studies conducted by several groups have established that porphyrogenic agents which caused elevations in chick-embryo liver delta-aminolaevulinate (ALA) synthase activity also increased the concentrations of the enzyme's RNA, and that haemin inhibited these elevations. We have determined in this study, using immune blot analyses, that administration in ovo of allylisopropylacetamide (AIA) in combination with diethyl 1,4-dihydro-2,4,6-trimethyl,3,5-pyridinedicarboxylate (DDC) increased the mass of ALA synthase in intestine and kidney of chick embryos. Furthermore, the molecular mass of the subunit of the enzyme in those tissues appeared identical with that of liver ALA synthase. Using a synthetic oligonucleotide complementary to ALA synthase mRNA, we determined by solution hybridization and Northern-blot analyses that AIA and DDC also increased the concentrations of ALA synthase mRNA in intestine and kidney and that testosterone elevated the concentration of the RNA in kidney. In analyses of RNA obtained from chick-embryo liver, intestine, kidney, heart, brain and lung, the probe bound primarily in each case to a single 2.3 kb RNA. Finally, the haem precursors ALA and FeCl3, when injected together into the fluid surrounding embryos, inhibited both the elevations in ALA synthase mass and RNA concentration brought about by porphyrogenic agents in liver, kidney and intestine. Thus the results indicated that: (1) certain porphyrogenic agents increased ALA synthase mass and RNA in chick-embryo intestine and kidney, in addition to liver; (2) ALA and FeCl3 inhibited the elevations; and (3) the sizes of ALA synthase's subunit as well as the enzyme's mRNA appeared identical, in each case, in all tissues examined. PMID- 2590169 TI - Dermatan sulphate proteoglycans of human articular cartilage. The properties of dermatan sulphate proteoglycans I and II. AB - Dermatan sulphate proteoglycans were purified from juvenile human articular cartilage, with a yield of about 2 mg/g wet wt. of cartilage. Both dermatan sulphate proteoglycan I (DS-PGI) and dermatan sulphate proteoglycan II (DS-PGII) were identified and the former was present in greater abundance. The two proteoglycans could not be resolved by agarose/polyacrylamide-gel electrophoresis, but could be resolved by SDS/polyacrylamide-gel electrophoresis, which indicated average Mr values of 200,000 and 98,000 for DS-PGI and DS-PGII respectively. After digestion with chondroitin ABC lyase the Mr values of the core proteins were 44,000 for DS-PGI and 43,000 and 47,000 for DS-PGII, with the smaller core protein being predominant in DS-PGII. Sequence analysis of the N terminal 20 amino acid residues reveals the presence of a single site for the potential substitution of dermatan sulphate at residue 4 of DS-PGII and two such sites at residues 5 and 10 for DS-PGI. PMID- 2590170 TI - Calcitriol enhances transcriptional activity of lysozyme and cathepsin D genes in U937 promonocytes. AB - Calcitriol (1,25-dihydroxyvitamin D3) has been reported to enhance the rate of synthesis of lysozyme [Rouis, Thomopoulos, Louache, Testa, Heroy & Titeux, (1985) Exp. Cell Res. 157, 539-543] and of cathepsin D [Stein, Braulke, von Figura & Hasilik (1987) Biol. Chem. Hoppe-Seyler 368, 413-418] in human promonocytes U937. In this study we show hat the hormone enhances the steady-state levels of cathepsin D and lysozyme mRNAs. The enhancement of the latter but not of the former is strongly inhibited by cycloheximide. The degradation rates of cathepsin D and lysozyme mRNAs as revealed in the presence of actinomycin D are not significantly affected by the treatment of the cells with calcitriol. In nuclei prepared from calcitriol-treated cells, an enhanced rate of synthesis of cathepsin D and lysozyme mRNA precursors is observed. These results suggest that in human promonocytes the rate of the transcription of cathepsin D and lysozyme genes is enhanced in the presence of calcitriol and that the regulation by the hormone of the transcription of lysozyme gene involves a short-lived or an induced protein. PMID- 2590171 TI - Cloning and amplified expression in Streptomyces lividans of the gene encoding the extracellular beta-lactamase of Actinomadura R39. AB - By using the promoter-probe plasmid pIJ424, genomic DNA fragments of Actinomadura R39 were shown to have promoter activity in Streptomyces lividans. The same 100 200-copy-number plasmid was used to clone in S. lividans TK24, the gene that encodes the Actinomadura R39 beta-lactamase. Gene cloning resulted in an amplified expression of the beta-lactamase when compared with the amounts of enzyme produced by the original strain (1 mg versus 0.008 mg.litre of culture-1). PMID- 2590172 TI - Metallothionein mRNA and protein induction by cadmium in peripheral-blood leucocytes. AB - To help to evaluate the role of metallothionein (MT) in peripheral-blood leucocytes, we examined MT protein and mRNA levels in these cells before and after exposure to CdCl2 in culture. Protein was assayed by 109Cd2+ binding, and RNA by dot-blot hybridization. MT was induced in both lymphocytes and adherent monocytes about 10-fold with a 12 h exposure to 10 microM-CdCl2, but absolute levels were 3-fold higher in monocytes: 57 x 10(5) (+Cd2+) versus 6 x 10(5) ( Cd2+) molecules/cell for monocytes; 18 x 10(5) (+Cd2+) versus 2 x 10(5) (-Cd2+) for lymphocytes. Polymorphonuclear cells expressed relatively little MT (0.6 x 10(5) molecules/cell), and this did not change with phorbol ester stimulation or exposure to Cd2+, arguing against a direct protective role for MT in activated neutrophils. MT mRNA levels corresponded qualitatively to expression of protein in these cells. Our data provide quantitative comparisons of leucocyte MT expression and regulation in the human population. Variation in both basal and induced MT mRNA levels reflects environmental or experimental (intra-individual) and possibly genetic (inter-individual) differences. PMID- 2590173 TI - Lipid metabolism during the initiation of lactation in the rat. The effects of starvation and tumour growth. AB - 1. The effects of starvation post partum (24 h) and tumour growth pre partum on the initiation of lactation in the rat were studied. 2. Tumour growth decreased food intake at 24 h, but not at 2 days post partum. 3. Pup growth rate increased with hyperphagia; starvation and tumour burden decreased pup growth, and starvation decreased maternal body weight. 4. Starvation decreased gastrointestinal-tract mass; tumour growth decreased gastrointestinal-tract and mammary-gland mass. 5. Mammary-gland DNA-synthesis rate was high immediately post partum, but decreased by day 3 of lactation; starvation and tumour burden decreased this rate, and also decreased gastrointestinal-tract DNA-synthesis rate. 6. Arteriovenous differences for glucose and lactate across the mammary gland did not change with time, nor were they affected by the tumour. Starvation decreased arterial glucose and lactate, and the gland extracted less glucose but produced lactate. 7. Mammary-gland lipogenesis was sensitive to starvation and to tumour growth. 8. In contrast with the gradual development of mammary-gland lipogenic enzyme activities, lipoprotein lipase activity was high in the gland by 2 days post partum; starvation or tumour burden decreased the activity. 9. The mammary gland is sensitive post partum to decreased food intake, and to tumour presence. The effects of the latter are apparently independent of hypophagia. PMID- 2590174 TI - Purification and characterization of recombinant human interleukin 4. Biological activities, receptor binding and the generation of monoclonal antibodies. AB - A synthetic gene coding for human interleukin 4 (IL-4) was cloned and expressed in Saccharomyces cerevisiae (baker's yeast) as a C-terminal fusion protein with the yeast prepro alpha-mating factor sequence, resulting in secretion of mature IL-4 into the culture medium (0.6-0.8 micrograms/ml). A protocol was developed for purification of this protein. Crude cell-free conditioned medium was passed over a concanavalin A-Sepharose affinity column; bound proteins were eluted and further purified by S-Sepharose Fast Flow cation exchange and C18 reverse-phase h.p.l.c. Highly purified IL-4 was obtained by this method (0.3-0.4 mg per litre of culture) with a recovery of 51%. Thermospray liquid chromatography-mass spectrometry showed the C-terminal N-glycosylation site to be largely unmodified, and also showed that the N-terminus of the purified recombinant IL-4 (rIL-4) was authentic. Thiol titration revealed no free cysteine residues, implying that there are three disulphide groups, the positions of which remain to be determined. We have characterized the biological activities of the purified rIL 4. This material is active in B-cell co-stimulator assays, T-cell proliferation assays and in the induction of cell-surface expression of CD23 (the low-affinity receptor for IgE) on tonsillar B-cells. Half-maximal biological activity of the rIL-4 was achieved at a concentration of 120 pM. We have radioiodinated rIL-4 without loss of biological activity and performed equilibrium binding studies on Raji cells, a human B-cell line. The 125I-rIL-4 bound specifically to a single class of binding studies on Raji cells, a human B-cell line. The 125I-rIL-4 bound specifically to a single class of binding site with high affinity (Kd = 100 pM) and revealed 1100 receptors per cell. Receptor-ligand cross-linking studies demonstrated a single cell-surface receptor with an apparent molecular mass of 124 kDa. Two monoclonal antibodies have been raised to the human rIL-4, one of which blocks both the biological activity of rIL-4 and binding to its receptor. PMID- 2590176 TI - Plasma-desorption mass spectrometry as an aid in protein sequence determination. Application of the method on a cuticular protein from the migratory locust (Locusta migratoria). AB - The complete amino acid sequence of a structural protein, protein 8, isolated from the pharate cuticle of the locust Locusta migratoria was determined. Protein 8 contains 148 amino acid residues and has an Mr of 15,224. By the extensive use of information obtained by plasma-desorption mass spectrometry (p.d.m.s.) it was possible to reduce the need for conventional sequence determination and to improve the reliability of the results. On the basis of the determined Mr of the intact protein all the peptides that constitute the complete sequence could be isolated from a time-course enzymic digestion. The isolated peptides were sequenced by using a combination of Edman degradation and carboxypeptidase digestion monitored by p.d.m.s. The alignment of the peptides was established from the time-course digestion and further verified by a second enzymic digestion. The primary structure of the protein consists of two hydrophilic and two hydrophobic regions. The hydrophobic regions are enriched in alanine, valine and proline and dominated by a repetitive sequence Ala-Ala-Pro-(Ala/Val). The sequence strengthens the view that the cuticle proteins belong to a unique family of structural proteins. PMID- 2590175 TI - Site of carbamoylation of bovine gamma-II-crystallin by potassium [14C]cyanate. AB - One possible route to cataract formation may be via the carbamoylation of lens proteins due to increased concentrations of cyanate in the body resulting from uraemia associated with renal failure and with severe diarrhoea. Carbamoylation of gamma-II-crystallin, which is found in the lens core, could alter the surface charge network of the molecules, resulting in aggregation, increased light scattering and hence cataract. We have attempted to locate the site(s) of carbamoylation in gamma-II-crystallin. gamma-II-Crystallin was isolated by gel chromatography and ion-exchange chromatography. gamma-II-Crystallin was then carbamoylated by incubation with potassium [14C]cyanate, followed by citraconylation and digestion with trypsin to give peptides that were separated by high-resolution ion-exchange chromatography. The amino acid compositions of the radioactive peptides were compared with the expected peptide composition for gamma-II-crystallin. The radioactive peptide compositions, which agreed with the theoretical peptides, all matched with the N-terminal region of gamma-II crystallin and had in common the presence of the N-terminal glycine residue. It appears that the alpha-amino group of the N-terminal glycine was the main site of carbamoylation. This site forms part of the charge network on the surface of gamma-II-crystallin. PMID- 2590177 TI - Glutathione transferases in the tapeworm Moniezia expansa. AB - Four forms of GSH transferase were resolved from Moniezia expansa cytosol by GSH Sepharose affinity chromatography and chromatofocusing in the range pH 6-4, and the presence of isoenzymes was further suggested by analytical isoelectric focusing. The four GSH transferase forms in the cestode showed no clear biochemical relationship to any one mammalian GSH transferase family. The N terminal of the major GSH transferase form showed sequence homology with the Mu and Alpha family GSH transferases. The major GSH transferase appeared to bind a number of commercially available anthelmintics but did not appear to conjugate the compounds with GSH. The major GSH transferase efficiently conjugated members of the trans-alk-2-enal and trans,trans-alka-2,4-dienal series, established secondary products of lipid peroxidation. PMID- 2590178 TI - Molecular-size-dependent variations in the proportions of chains with high binding affinities for antithrombin in rat skin heparin proteoglycans. AB - Approximately half of all rat skin heparin proteoglycans have polysaccharide chains that have no sites with high binding affinity for antithrombin. The rest have chains with high-affinity antithrombin-binding-site densities ranging from zero to five sites per chain, with a high degree of variation. Proteoglycans vary in size because of diversity in the number of chains per molecule; the relationship between proteoglycan size and high-affinity antithrombin-binding site density has not been studied previously. Polydisperse heparin proteoglycans from rat skin, labelled biosynthetically with 35S, were fractionated by gel filtration on Bio-Gel A-150m and arbitrarily divided into five fractions of decreasing average molecular size. Fractionation of these products on antithrombin-agarose showed that the proportion of proteoglycans with high affinity for antithrombin decreased from 39% to 25% as molecular size decreased. However, as the molecular size of high-affinity proteoglycans decreased, the proportion of their chains that had high affinity increased from 29% to 59%. Therefore molecular size is a significant factor in determining the proportion of high-affinity chains in heparin proteoglycans. A model of heparin biosynthesis is proposed in which areas of specific enzyme activity that control the synthesis of the antithrombin-binding-site sequence are sparsely and nonrandomly distributed on mast-cell Golgi membranes. It is postulated that the likelihood of a developing proteoglycan encountering one of these hypothetical areas is molecular size-dependent. PMID- 2590180 TI - Purification and characterization of acetohydroxyacid reductoisomerase from spinach chloroplasts. AB - Acetohydroxyacid reductoisomerase was purified over 400-fold to a specific activity of 62 nkat.mg-1, with 2-aceto-2-hydroxybutyrate as substrate, from the stroma of spinach leaf chloroplasts. The enzyme was not intrinsically membrane bound. The native enzyme was a tetramer with a subunit Mr of 59,000. The activity was optimum between pH 7.5 and 8.5. The apparent Km for 2-acetolactate was 25 microM and for 2-aceto-2-hydroxybutyrate was 37 microM. The enzyme required Mg2+ and the Vmax. was attained at physiological Mg2+ concentrations. NADP+ competitively inhibited the reaction when NADPH was the varied substrate. The native enzyme eluted from Mono-Q ion-exchange resins as three distinct peaks of activity. This elution pattern was preserved when the peaks were combined, dialysed and re-chromatographed. Each form exhibited identical Mr of 59,000 after SDS/polyacrylamide gel electrophoresis (PAGE), whereas they were easily distinguishable from each other after PAGE under non-denaturing conditions. These results provide evidence for the existence of multiple forms of acetohydroxyacid reductoisomerase in chloroplasts isolated from spinach leaves. PMID- 2590179 TI - Alkyl and aromatic isocyanide binding to haem complexes. AB - Equilibrium constants for the binding of ethyl (EIC), n-butyl (BIC), p toluenesulphonylmethyl (TMIC) and 2,6-dimethylphenyl isocyanides (DIMPI) to an imidazole-haem complex in toluene and aqueous detergent micelle solutions were determined. In contrast to an earlier study, which indicated that the large affinities of myoglobin for binding DIMPI and 2,6-diethylphenylisocyanide (DEPI) relative to EIC were due to an electronic effect, the present study shows a similarity in binding constants for EIC, BIC, and DIMPI to the imidazole-haem complex in toluene, suggesting no such electronic effect is present. The measured hydrophobic effect (KDIMPI/KEIC = 11) cannot account for the large binding constant reported for DIMPI relative to the binding of EIC to myoglobin. Based on the results of these model studies, the equilibrium binding constant for DIMPI to myoglobin has been re-measured and the standard free energy of binding has been analysed by a more recent method. PMID- 2590181 TI - 4-Hydroxynonenal induces a DNA-binding protein similar to the heat-shock factor. AB - By using a gel mobility assay, we have shown that treatment of HeLa cells with 4 hydroxynonenal, a major product of the peroxidation of membrane lipids and an inducer of heat-shock proteins, has the same effect as heat shock in causing the appearance of a protein which binds to the sequence of DNA specific for the induction of heat-shock genes. Lipoperoxidation and heat exposure seem to share a common mechanism of specific gene activation. PMID- 2590182 TI - The permeability of lysosomes to sugars. Effect of diethylstilbestrol on the osmotic activation of lysosomes induced by glucose. AB - We have investigated the effect on the osmotic activation of rat liver lysosomes, by glucose penetration, of different substances known to inhibit the glucose transport through the plasma membrane. Diethylstilbestrol is the most efficient, particularly when purified lysosomes are used. It has no effect on osmotic activation induced by hypo-osmotic sucrose or by iso-osmotic KCl. It is proposed that diethylstilbestrol reacts with specific sites involved in the glucose translocation through the lysosomal membrane. These sites could not be identified by binding experiments, presumably owing to the considerable unspecific binding of the compound to the membrane. PMID- 2590183 TI - Automated isocratic high-performance liquid chromatography of inositol phosphate isomers. AB - Isomers of inositol phosphates from biological samples can be analysed by anion exchange h.p.l.c., by using isocratic elution with phosphate buffers. The method involves the preliminary processing of the extracted samples with conventional soft-gel anion-exchange resins, including the commonly used Dowex resins, followed by direct analysis with h.p.l.c. of a portion of relevant fractions. Run times (up to 20 min) and collected fraction numbers (up to 24) are minimal, so that if the method is used in conjunction with automated h.p.l.c. injection a high throughput of samples is achieved. PMID- 2590184 TI - Characterization of the submitochondrial compartments: study of the site of synthesis of dolichol and dolichol-linked sugars. AB - The fractionation of mitochondrial membranes on discontinuous sucrose gradient leads to the obtaining of free outer membranes, free inner membranes and two distinct membrane contact site populations characterized as follows. Only outer membrane contact sites and inner membrane contact sites bind hexokinase. Outer membranes and outer membrane contact sites are cholesterol-rich fractions. The endogenous dolichol content is twice fold higher in outer membranes and outer membrane contact sites than in inner membranes and inner membrane contact sites, only the biosynthesis of dolichol in inner membrane contact sites is not stimulated by addition of exogenous [14C]-IPP and FPP. The glycosylation of endogenous dolichol from labeled nucleotide-sugars (UDP-GlcNAc, GDP-Man and UDP Glc) leads to the synthesis of dolichol-pyrophosphoryl-sugars and dolichol monophosphoryl-sugars with the rate of synthesis proportional to the dolichol content of each submitochondrial fraction. PMID- 2590185 TI - Isolation and characterization of a cDNA clone encoding human aromatic L-amino acid decarboxylase. AB - The nucleotide sequence of a cDNA clone that includes the entire coding region of human aromatic L-amino acid decarboxylase gene is presented. A human pheochromocytoma cDNA library was screened using an oligonucleotide probe which corresponded to a partial amino acid sequence of the enzyme purified from the human pheochromocytoma. The isolated cDNA clone encoded a protein of 480 amino acids with a calculated molecular mass of 53.9 kDa. The amino acid sequence Asn Phe-Asn-Pro-His-Lys-Trp around a possible cofactor (pyridoxal phosphate) binding site is identical in human, Drosophila, and pig enzymes. PMID- 2590186 TI - Measurement of CA2+ transients using simultaneous dual-emission microspectrofluorimetry and electrophysiology in individual pituitary cells. AB - Cytosolic free calcium concentration, [Ca2+]i, was monitored in individual pituitary GH3B6 cells, loaded with the fluorescent Ca2+ indicator indo 1 either by internal perfusion through a patch clamp pipette or by exposure to indo 1 acetoxymethyl ester, with the use of a dual-emission apparatus for microspectrofluorimetry. This system was sensitive enough to allow on-line monitoring of [Ca2+]i (from the ratio of fluorescent intensities) which could be combined simultaneously with whole-cell patch clamp recordings. The following situations were examined: (a) [Ca2+]i oscillations due to action potential firing, and (b) rapid transient elevations of [Ca2+]i triggered by voltage dependent Ca2+ current. The results indicate that monitoring of [Ca2+]i at the single cell level with indo 1 provides a powerful means to study the [Ca2+]i regulation in pituitary cells, which should be applicable to many other cell types. PMID- 2590187 TI - Phorbol esters inhibit apoptosis in IL-2-dependent T lymphocytes. AB - The effect of phorbol esters on the proliferation and survival of interleukin 2(IL-2)-dependent cells was studied using an IL-2-dependent T cell line (CTLL-2) and blasts of BALB/c mouse spleen cells stimulated with Concanavalin A. Addition of phorbol 12,13-dibutyrate (PDBu) to CTLL-2 or ConA blasts induces a mitogenic response which is 25-40% of that elicited by IL-2. Interleukin 2 deprivation leads to a marked decline in the number of viable cells (50% of CTLL-2 cells have died after 8-10 hours incubation in IL-2-free medium). The mechanism of cell death seems to correspond to the suicide process known as apoptosis since an early degradation of DNA into oligonucleosome-size fragments could be observed after removal of the growth factor. When present, PDBu inhibits both the activation of the endonuclease and the development of the cell death process in CTLL-2 cells and ConA-blasts deprived of IL-2. Taken together, our results suggest that the tumor promoters phorbol esters inactivate in T cells the mechanism of cell elimination triggered by IL-2 deprivation and may help to explain why transformation of T cells decreases or even abolishes their requirements of IL-2 for survival and growth. PMID- 2590188 TI - NMR investigation on the structure and conformation of 3'-azido-2',3' dideoxyribosylthymine (AZT), an inhibitor of the HIV (AIDS virus). AB - 1H and 13C NMR study of 3'-azido-2',3'-dideoxyribosylthymine (AZT), an inhibitor of HIV (human immunodeficiency virus) replication, has been undertaken. Modified Karplus relations have been used to obtain the molecular structure from the indirect coupling constants. NMR results are consistent with an anti glycosyl angle, a sugar pucker with equilibrium between C2'-endo and C3'-endo geometries and a predominantly g+ conformation about C4'-C5' bond. These results are in variance with those obtained in the solid state by X-ray diffraction studies. PMID- 2590189 TI - The transport of L-arginine in Chinese hamster ovary cells. AB - The transport of L-arginine has been characterized in Chinese hamster ovary cells (CHO). In the absence of Na+ the influx of the amino acid decreased. Both in the presence and in the absence of Na+ L-arginine influx was trans-stimulated and cis inhibited by cationic amino acids. The amino acid entered CHO cells through an apparently non saturable mechanism and a single saturable agency whose Km increased in the absence of Na+. These results indicate that the agency devoted to transport cationic amino acids in CHO cells resembles system y+, the Na+ independent route that transports cationic amino acids in a number of mammalian models, although its activity is lowered by the replacement of extracellular sodium. PMID- 2590190 TI - Demonstration of a basic fibroblast growth factor-like molecule in mouse hepatic endothelial cells. AB - We have investigated whether isolated mouse hepatic sinusoidal endothelial cells (HSEC) synthesized basic FGF. HSEC lysate was fractionated by heparin-Sepharose chromatography. A peak of mitogenic activity for Balb/c 3T3 fibroblasts was eluted with 3M NaCl. Several arguments suggested that the mitogenic factor was related to bFGF: a) its affinity for heparin; b) the loss of its mitogenic activity by heating at 65 degrees C, which was prevented in the presence of heparin; c) the abolition of its mitogenic activity in the presence of protamine sulfate; d) finally, its mitogenic effect was reduced in the presence of antibody to bFGF. These data demonstrate the presence of a bFGF-like molecule in HSEC. This molecule could be involved in the regulation of the neighboring Ito cell proliferation. PMID- 2590191 TI - Change in transferrin receptor distribution in regenerating rat liver. AB - Partial hepatectomy results in an increase in the ability of the liver cells to bind 125I-labeled transferrin to surface receptors. Scatchard analysis of the binding of transferrin in regenerating rat liver indicates that this increase was due to an increase in the number of transferrin receptors on the cell surface. When we measured total cellular transferrin receptor number, we found that control and regenerating livers had identical amounts of receptor number. The increase in the surface receptor number is apparently due to the translocation of intracellular transferrin receptor to the cell surface. PMID- 2590193 TI - Structural analysis of the gene for human acidic fibroblast growth factor. AB - Genomic clones derived from the gene for human acidic fibroblast growth factor (aFGF) have been isolated. Nucleotide sequence analysis of these clones revealed that the coding region of the human aFGF gene is interrupted by two introns, located at precisely homologous locations to introns in four other members of the FGF gene family, strongly indicating a common evolutionary origin for these genes. Northern blot analyses of the multiple aFGF transcripts found in serum stimulated human foreskin fibroblasts indicated that the aFGF gene also contains a third intron, lying in the 5' untranslated region. PMID- 2590192 TI - Isolation and sequencing of a cDNA clone encoding 96 kDa sialoglycoprotein in rat liver lysosomal membranes. AB - We isolated and sequenced LGP 96, a cDNA clone corresponding to the entire coding sequence of the rat liver lysosomal membrane sialoglycoprotein with an apparent Mr of 96 K, LGP 96. The deduced amino acid sequence indicates that LGP 96 consists of 411 amino acid residues (Mr 45,163) and the 26 NH2-terminal residues presumably constitute a cleavable signal peptide. The major portion of LGP 96 resides on the luminal side of the lysosome and bears a large number of N-linked heavily sialylated complex type carbohydrate chains, giving the mature molecule of 96 kDa. The protein has 17 potential N-glycosylation sites and 32.1 and 65.3% sequence similarities in amino acid to LGP 107 and human lamp-2, respectively. The glycosylation sites are clustered into two domains separated by a hinge-like structure enriched with proline and threonine. LGP 96 possesses one putative transmembrane domain consisting of 24 hydrophobic amino acids near the COOH terminus and contains a short cytoplasmic segment constituting 12 amino acid residues at the COOH-terminal end. Comparison of LGP 96 and recently cloned lysosomal membrane glycoprotein sequences reveals strong similarity in the putative transmembrane domain and cytoplasmic tail. It is very likely that these portions are important for the targeting of molecules to lysosomes. A comparison of LGP 96 and LGP 107 showed numerous structural similarities. PMID- 2590194 TI - Proposed mechanism for the bacterial bioluminescence reaction involving a dioxirane intermediate. AB - We propose here a verifiable mechanism for the bacterial bioluminescence reaction involving a dioxirane intermediate. Participation of the dioxirane predicts either formation of an excited carbonyl, rather than the flavin, as the primary excited state in the reaction, or, through a CIEEL mechanism, the C4a hydroxyflavin or the chromophore of a secondary emitter protein could become excited. We propose energy transfer from the primary excited state to the C4a hydroxyflavin in the absence of the lumazine protein or the yellow fluorescence protein, while in the presence of either of the secondary emitter proteins, excitation energy would be transferred to the second protein-bound chromophore. The mechanism is similar to other currently discussed mechanisms, except in the final steps leading to the primary excited state. The mechanism is consistent with the known details of the reactions of dioxiranes and of flavins and with recent studies of the secondary emitter proteins and bacterial luciferases. PMID- 2590195 TI - Butyrate increases catalase activity and protects rat pulmonary artery smooth muscle cells against hyperoxia. AB - A protective effect of butyrate against hyperoxia was found with adult rat pulmonary artery smooth muscle cells. Butyrate (5mM) when added just prior to the hyperoxic exposure (95%) markedly decreased lactate dehydrogenase release from cells during 68 hours of exposure (22% release with butyrate versus 98% without). The uptake and reduction of a tetrazolium compound as another index of cell viability also showed similar improvement with butyrate. Butyrate was associated with a striking increase of catalase to three times the control in the air exposed group while GSH content and the activities of superoxide dismutase and glutathione peroxidase were not significantly changed. In the groups exposed to hyperoxia alone, both enzyme activities were decreased compared to the air exposed controls. When butyrate was present with hyperoxia, the superoxide dismutase was maintained closer to the air exposed control values and the catalase activity remained nearly twice as high as the air exposed control cells. These results suggest that butyrate protects rat pulmonary artery smooth muscle cells from hyperoxia by increasing catalase activity which may help to preserve superoxide dismutase activity. This may be a good model to determine the biological significance of catalase and its interrelationships with other antioxidant systems within the cell. PMID- 2590196 TI - The autoinhibitor of cell fusion in Dictyostelium inhibits calmodulin. AB - During early sexual development in Dictyostelium discoideum cell and pronuclear fusion are negatively regulated by an endogenous autoinhibitor. Here, the autoinhibitor was partially purified from the culture medium and found to inhibit both cell and pronuclear fusion while augmenting gamete numbers. These developmental effects suggested that calmodulin might be an intracellular target for the autoinhibitor. In support of this data, the partially purified autoinhibitor inhibited the calmodulin-dependent activation of phosphodiesterase in a dose-dependent manner, but had no effect on either a calmodulin-insensitive form of phosphodiesterase or the calmodulin-independent enzymes acid and alkaline phosphatase. Thus, the autoinhibitor of sexual development in Dictyostelium discoideum appears to regulate cell and pronuclear fusion at least in part by a direct effect on calmodulin. PMID- 2590197 TI - 2',3'-didehydro-2',3'-dideoxy-5-chlorocytidine is a selective anti-retrovirus agent. AB - 2',3'-Didehydro-2',3'-dideoxy-5-chlorocytidine (D4CC) is, in contrast with 2',3' dideoxy-5-chlorocytidine (ddClCyd) and 2',3'-didehydro-2',3'-dideoxy-5 chlorouridine (D4CU), a potent and selective inhibitor of the replication of human immunodeficiency virus (HIV) types 1 and 2, simian immunodeficiency virus (SIV) and simian AIDS related virus (SRV). D4CC is a poor inhibitor of the phosphorylation of [5-3H]2'-deoxycytidine (dCyd) by partially purified MT-4 cell dCyd kinase (Ki: 612 microM). The findings that (i) D4CC has little, if any, affinity for MT-4 cell Cyd/dCyd deaminase, (ii) D4CU is not antivirally active and (iii) the antiretroviral action of D4CC can be reversed by dCyd, but not dThd, indicate that D4CC is antivirally active as its Cyd metabolite (D4CC 5' triphosphate) and does not need to be deaminated (to the corresponding Urd metabolite) to exert its antiretroviral action. PMID- 2590198 TI - Stabilization of disulfide linkage in drug-polymer-immunoglobulin conjugate by microenvironmental control. AB - The stability of disulfide linkage in the conjugate composed of the anti-cancer agent adriamycin, poly(ethylene glycol)-poly(aspartic acid) block copolymer, and immunoglobulin G was studied. The disulfide linkage between the block copolymer and immunoglobulin G was found to be resistant to reduction with dithiothreitol (DTT). This extraordinary resistance is considered to be brought about by steric hindrance of the poly(aspartic acid) chain binding adriamycin. PMID- 2590199 TI - A new mutation causing familial amyloidotic polyneuropathy. AB - The DNA from an individual with familial amyloidotic polyneuropathy was examined. It did not possess any of the mutations which have previously been associated with familial amyloidotic polyneuropathy. However, a novel 7.0 kb Sph I restriction fragment was discovered, and the mutation creating it was localized to exon 3 of the transthyretin gene. This mutation was inherited from a parent, and may result in an amino acid substitution for glu89, his90 or ala91. The patient's transthyretin has a lower pI than normal transthyretin. PMID- 2590200 TI - Characterization of the 5' flanking region of rat glucokinase gene. AB - The rat glucokinase (GK) gene containing the first exon was isolated and its 5' flanking region was characterized by the bacterial chloramphenicol acetyltransferase (CAT) assay. A transient expression assay with a series of 5' deletion constructs (-5.5 k to -48) of GK-CAT fusion genes indicated that the 5' flanking sequence up to nucleotide -87 was sufficient for promoter activity in adult rat hepatocytes, but its activity was much weaker than that of the SV40 enhancer/promoter. Similar promoter activity was also detected in dRLh-84 hepatoma cells, which do not express glucokinase. Insulin treatment caused no change in the CAT activity of hepatocytes transfected with the fusion genes. These results suggest that the 5' flanking region of the glucokinase gene up to 5.5 k does not contain enhancer elements responsible for tissue-specific expression or insulin regulation. PMID- 2590201 TI - Stable high level expression of human thyroid peroxidase in cultured Chinese hamster ovary cells. AB - An expression plasmid containing both human thyroid peroxidase and mouse dihydrofolate reductase cDNAs was transfected into chinese hamster ovary cells. The stably transformed cells constitutively expressed immunoreactive thyroid peroxidase on the cell surface. These cells were further used to establish a subline producing a large amount of thyroid peroxidase by selecting clones resistant to methotrexate. The molecular weight of the expressed thyroid peroxidase was the same as purified human thyroid peroxidase. This expressed protein had peroxidase activity when determined by guaiacol oxidation. Furthermore, the expressed thyroid peroxidase was immunoreactive to sera of patients with autoimmune thyroid disease in which autoantibodies to thyroid peroxidase appeared. PMID- 2590202 TI - Effect of anthracycline antibiotics on the reconstituted mitochondrial tricarboxylate carrier. AB - The effect of anthracycline antibiotics on the activity of the partially purified and reconstituted tricarboxylate carrier system of the rat liver mitochondria was studied. It was found that the citrate/citrate exchange activity is inhibited by Br-daunomycin and with less potency by doxorubicin, daunomycin, epirubicin and idarubicin. The inhibition of the citrate transport activity is concentration and time-dependent. Cardiolipin protects against the inhibition by Br-daunomycin and the reconstituted citrate transport activity depends upon the ratio of cardiolipin/Br-daunomycin. PMID- 2590203 TI - Cloning of the bovine pancreatic cholesterol esterase/lysophospholipase. AB - A cDNA clone encoding for the bovine pancreatic cholesterol esterase has been sequenced. Pancreatic cholesterol esterases hydrolyze dietary cholesterol esters to cholesterol and free fatty acids, which are then absorbed from the gut. Northern blots reveal that the positive signal at 1.9 kilobases is much more intense in the cow than in calf pancreas, indicating that the induction of the enzyme is due to increased transcription or stability of mRNA. The primary structure of this enzyme is similar to that of the rat pancreatic lysophospholipase. We found that homogeneous human and bovine pancreatic cholesterol esterases have high levels of lysophospholipase activity, indicating that these two activities reside within the same protein. Therefore, the metabolism of dietary neutral lipids and polar lipids may be linked through a single enzyme. PMID- 2590204 TI - Molecular cloning of a small prostate protein, known as beta-microsemenoprotein, PSP94 or beta-inhibin, and demonstration of transcripts in non-genital tissues. AB - In order to study the gene expression of the seminal plasma protein beta microseminoprotein, also known as PSP94 and beta-inhibin, clones encoding this protein were isolated from a cDNA library constructed in lambda gt11. Nucleotide sequencing confirmed the structure of a previously cloned cDNA. By northern blot analysis identical sized transcripts were demonstrated in the prostate, the respiratory (tracheal, bronchial and lung) tissues and the antrum part of the gastric mucosa. Thus, the protein is not primarily associated with male reproductive function. Although probably of no physiological significance, a slight structural similarity to the ovarian inhibin beta-chains was identified in the C-terminal half of the molecule. PMID- 2590205 TI - The effect of asparagine and adenine on the glutamine requirement for growth of human peripheral lymphocytes. AB - Quantitative growth responses of lymphocytes directly isolated from individual subjects in a newly developed chemically-defined, protein-free medium are used to demonstrate that supplements of both L-asparagine and a purine source, but neither alone, significantly reduce the quantitative requirement for L-glutamine for growth. This system is useful for exploring individual differences in quantitative glutamine requirements and adequacy of asparagine and purine biosynthesis. PMID- 2590206 TI - Multiple deletions in mitochondrial DNA at direct repeats of non-D-loop regions in cases of familial mitochondrial myopathy. AB - Muscle mitochondrial DNAs from two brothers with mitochondrial myopathy associated with peripheral neuropathy had multiple deletions, most of which started in non-D-loop regions, unlike in an autosomal dominant mitochondrial myopathy (Zeviani, M. et al., Nature 339, 309 (1989)). The non-D-loop regions with deletions were amplified by the polymerase chain reaction and the resulting fragments were subcloned and then sequenced. At least 12 deletions of different lengths in different sites were found. However, all the deletions were flanked by short direct repeats (4-12 base pairs). PMID- 2590207 TI - Molecular cloning and characterization of a novel marsupial milk protein gene. AB - The tammar wallaby (Macropus eugenii) produces two different types of milk; "early" milk for the first 180 days and "late" milk for the remaining 150 days of lactation. We report the cloning of the cDNA of a novel whey protein, Late Lactation Protein (LLP), which is produced during the late phase of lactation. The cDNA was cloned using an oligonucleotide probe deduced from the published partial protein sequence. The cDNA encodes an open-reading frame of 176 amino acids of which the first 18 residues represent a signal peptide. Northern blot analysis revealed a 1kb transcript in late phase lactation but not in the early phase. PMID- 2590208 TI - Selective low level of protein kinase C isozyme in a tumor promoter-dependent mouse leukemia cell line. AB - It was found that the activity of protein kinase C in the tumor promoter dependent cell line (A65T) was significantly lower than that in the independent cell line (A65IND) which was mutated from the dependent cell line. On the other hand, there was no significant difference between these cell lines with regard to cAMP-dependent protein kinase activity. It was found that the maximal binding capacity of [20-3H]phorbol-12,13-dibutyrate of the tumor promoter-dependent cells is lower than that of the independent cells with similar affinities of the two cell lines. Moreover, we found that the level of immunoreactive antigen with monoclonal antibody for type III of protein kinase C in A65T cells was significantly lower than that in the A65IND cells. Thus, this selective lower level of type III of protein kinase C in A65T cells, as compared with A65IND cells means that this difference may be linked to its tumor promoter-dependent cell proliferation. PMID- 2590209 TI - Lens crystallin changes associated with amphibian metamorphosis: involvement of a beta-crystallin polypeptide. AB - Lens crystallins isolated from the tadpole and frog lenses were compared with regard to the developmental changes of crystallin compositions. The major changes during the process of metamorphosis were (1) the total contents of alpha- and gamma-crystallins decrease from more than 70% to less than 60% and (2) one of the major beta-crystallin polypeptides increases from less than 1% to about 6% and (3) an amphibian-specific rho-crystallin also increases from about 6% to more than 10% of total soluble proteins of the lens. We have characterized the metamorphosis-dependent beta-crystallin polypeptide by peptide mapping and sequence determination of the protease-digested fragments. This polypeptide showed very high sequence homology to that of the major beta Bp-crystallin chain reported for the mammalian lenses. The changes of the relative abundance of various crystallins and the gradually-elevated levels of the expression of this beta Bp-like crystallin in the developing lens during metamorphosis may also have some bearing on the maintenance of lens stability in the adult frog lenses. PMID- 2590210 TI - Differentiative action of K252a on protein kinase C and a calcium-unresponsive, phorbol ester/phospholipid-activated protein kinase. AB - The Triton X-100 extract of the particulate fraction of porcine spleen contains a protein kinase which can be activated by phospholipid and the phorbol ester TPA but does not respond to phospholipid and calcium. The partially purified kinase has a molecular weight of 76 kDa (p76-kinase) and hence is somewhat smaller than the similarly behaving p82-kinase from mouse epidermis and spleen. The p76-kinase shows strong autophosphorylation. The protein kinase inhibitor K252a clearly differentiates between the Ca2+-unresponsive p76-kinase and Ca2+-responsive PKC. At concentrations of up to 5 x 10(-7)M it fails to suppress p76-kinase-catalyzed autophosphorylation and histone phosphorylation, but it inhibits PKC-catalyzed phosphorylation up to 50%. The IC50 values of K252a regarding PKC and the p76 kinase differ by two orders of magnitude. At low concentrations, K252a appears to slightly activate further TPA-activated p76-kinase. It is not able, however, to replace TPA and to stimulate the p76-kinase in the presence of phospholipid alone. PMID- 2590211 TI - Polymerization of factor B of the alternative complement pathway via disulfide bond(s) in the presence of Cu2+ and stimulation by C3b, the major fragment of C3. AB - Factor B(B) of the alternative complement pathway has been found to dimerize via disulfide bond(s) in the presence of CuCl2. Poly B has no B activity. The Bb fragment was also dimerized, indicating that one free sulfhydryl group on the Bb portion might be involved in polymerization. The Ba fragment was not dimerized. C3b, the major fragment of C3, has the capacity to stimulate polymerization of B. Incubation of C3b, B and factor D in the presence of Mg2+ and Cu2+ resulted in the formation of poly B and diminished cleavage of B. These results suggest that polymerization of B due to Cu2+ might be partly responsible for the impairment of C3 convertase activity of the alternative pathway. PMID- 2590212 TI - Conformational studies of two isomeric ring-expanded purine nucleosides and their 5'-mono- and -diphosphate derivatives. AB - The nucleosides Ia and IIa exist in syn and anti conformations, respectively, both in solid state and solution. Compound Ia undergoes significant conformational change, accompanied by increased population of the anti conformer, upon conversion to the corresponding 5'-mono- and- diphosphate derivatives, whereas conformation of IIa remains reasonably constant between nucleoside and nucleotides. While Ia possessed the C2'-endo-C3'-exo geometry, IIa had the opposite C2'-exo-C3'-endo conformation. The C5' of the two nucleosides bore axial and equatorial conformations, respectively. PMID- 2590213 TI - A gastrin-releasing peptide antagonist containing A psi (CH2O) amide bond surrogate. AB - The [Leu26-psi(CH2O)Leu27] derivative of N-Ac-GRP20-27-peptide amide was prepared and evaluated as a gastrin-releasing peptide antagonist. This psi(CH2O) derivative was found to be a more potent inhibitor of [3H-Phe15]GRP15-24NH2 binding and N-Ac-GRP20-27NH2 induced mitogenesis in Swiss 3T3 fibroblasts than the related nitrogen analog [Leu13-psi(CH2NH)Leu14] bombesin. Possible reasons for the improved activity of the (CH2O) insert relative to the (CH2NH) group include increased hydrophobicity and a reduced tendency of the oxygen derivative to form hydrogen bonds. PMID- 2590214 TI - Biochemical characterization of a sterol mutant plant regenerated from a tobacco callus resistant to a triazole cytochrome-P-450-obtusifoliol-14-demethylase inhibitor. AB - We report here, for the first time, the biochemical characterization of a plant mutant impaired in sterol biosynthesis. A fertile plant was regenerated from a tobacco callus resistant to LAB170250F, a potent inhibitor of the cytochrome-P450 obtusifoliol-14-demthylase. The resistant callus and the leaves from the regenerated plant are characterized by profound qualitative and quantitative changes in their sterol content. Self-fertilization of this plant yielded seeds with the same biochemical features, indicating that the new phenotype is of mutational origin. PMID- 2590215 TI - Molecular cloning of the cDNA coding for proline-rich protein (PRP): identity of PRP as C4b-binding protein. AB - Proline-rich protein (PRP) is a plasma protein with a high proportion of proline residues and possessing lipid-binding properties. In order to clarify its structure, a human liver cDNA library was screened using anti-PRP antiserum. Several overlapping phage cDNA clones were isolated and the total nucleotide sequence of the cDNA, 2178 bp in length, was analyzed. The amino acid composition of PRP deduced from the cDNA was essentially the same as that reported for PRP. In a homology search, the cDNA sequence was almost completely the same as the previously reported cDNA sequence of C4b-binding protein. Furthermore, the reported molecular weights of the two proteins under both reduced and unreduced conditions were quite alike. These findings indicate that PRP is identical with C4bp. PMID- 2590216 TI - Transforming growth factor-beta induces hemoglobin synthesis in a human erythroleukemia cell line. AB - We have examined the effects of TGF beta 1 and TGF beta 2 on the HEL human erythroleukemia cell line. It was observed that TGF beta 1 and 2 induced hemoglobin synthesis in these cells without causing a significant negative effect on cell proliferation. The cell surface markers glycophorin A and transferrin receptor that are associated with erythroid differentiation were also increased. This cell line may provide a model system in which to study the regulation of globin gene expression by a physiological growth factor known to act on hemopoietic cells. PMID- 2590217 TI - Monospecific antibodies against a synthetic peptide predicted from the alpha-3 nicotinic receptor cDNA inhibit binding of [3H]nicotine to rat brain nicotinic cholinergic receptor. AB - Polyclonal antibodies were raised against a synthetic decapeptide (designated S3) predicted from a segment of the alpha-3 subunit cDNA (amino acid residues 130 139) encoding the rat brain nicotinic cholinergic receptor. This segment was selected because it may be proximate to the nicotine/acetylcholine-binding site of the receptor (1). By radioligand binding assays and sucrose density gradient centrifugation, these monospecific antibodies were shown to inhibit the binding of [3H]nicotine to both the large molecular weight rat brain receptor (240 kDa) and to an SDS-disaggregated nicotine-binding subunit species (80 kDa), in a dose dependent manner. The neutralizing effect of the anti-S3 antibodies supports the view that this region of the protein is closely related to the agonist binding site. PMID- 2590218 TI - Selenium modulates peroxidation in the absence of glutathione peroxidase in Musca domestica. AB - Adult houseflies fed a low-selenium diet showed a 73% decrease in total Se compared to those given 1.0 ppm Se in their drinking water. This decrease was associated with a 84.4% increase in thiobarbituric acid reactants and a 16.3% increase in conjugated dienes. These increases were unrelated to activities of glutathione S-transferases, superoxide dismutases and catalase and to levels of reduced and oxidized glutathione, all of which were unaltered by Se deficiency. Since houseflies lack glutathione peroxidase, Se apparently modulates peroxidation in these animals independent of the antioxidant enzymes and glutathione. PMID- 2590219 TI - Cloning and sequence analysis of a rat liver cDNA encoding hydroxysteroid sulfotransferase. AB - Nothing has been known of the cDNAs encoding sulfotransferases (STs) that catalyze sulfation of steroids and xenobiotics. In the present study, a female Sprague-Dawley (SD) rat liver cDNA library was screened with rabbit anti-serum raised against hydroxysteroid ST a (STa) purified from female SD rat liver cytosol. The cDNA isolated from the library consisted of 1,028 base pairs which had an open reading frame of 852 base pairs encoding the entire rat ST subunit of 284 amino acids. The N-terminal amino acid sequences of STa and the rat liver hydroxysteroid ST, bile acid ST I, both elucidated previously by the chemical method, had a strong homology with that deduced from the cDNA. Northern blot analysis of total RNAs from female and male rat livers showed a marked sex difference (female much greater than male) in the expressed level of the mRNA for the predicted ST subunit protein. A remarkable sex difference (female much greater than male) was also observed by immuno-blot analysis in the level of the hydroxysteroid ST protein(s) cross-reacting with the anti-serum in the rat liver cytosols. PMID- 2590220 TI - Identification of angiotensin II receptor subtypes. AB - We have demonstrated the existence of two distinct subtypes of the angiotensin II receptor in the rat adrenal gland using radioligand binding and tissue section autoradiography. The identification of the subtypes was made possible by the discovery of two structurally dissimilar, nonpeptide compounds, DuP 753 and EXP655, that show reciprocal selectivity for the two subtypes. In the rat adrenal cortex, DuP 753 inhibited 80% of the total AII binding with an IC50 value on the sensitive sites of 2 x 10(-8) M, while EXP655 displaced only 20%. In the rat adrenal medulla, EXP655 gave 90% inhibition of AII binding with an IC50 value of 3.0 x 10(-8) M, while DuP 753 was essentially inactive. The combination of the two compounds completely inhibited AII binding in both tissues. PMID- 2590221 TI - Enzyme catalysed non-oxidative decarboxylation of aromatic acids. II. Identification of active site residues of 2,3-dihydroxybenzoic acid decarboxylase from Aspergillus niger. AB - In order to understand the mechanism of decarboxylation by 2,3-dihydroxybenzoic acid decarboxylase, chemical modification studies were carried out. Specific modification of the amino acid residues with diethylpyrocarbonate, N bromosuccinimide and N-ethylmaleiimide revealed that at least one residue each of histidine, tryptophan and cysteine were essential for the activity. Various substrate analogs which were potential inhibitors significantly protected the enzyme against inactivation. The modification of residues at low concentration of the reagents and the protection experiments suggested that these amino acid residues might be present at the active site. Studies also suggested that the carboxyl and ortho-hydroxyl groups of the substrate are essential for interaction with the enzyme. PMID- 2590222 TI - Stimulation of anchorage independent proliferation of human adrenocortical carcinoma cells by inhibition of cholesterol biosynthesis. AB - Proliferation of SW13 human adrenocortical carcinoma cells under anchorage independent conditions was stimulated in a dose-dependent manner by treatment with the cholesterol biosynthesis inhibitor mevinolin. Induction of 3-hydroxy-3 methylglutaryl coenzyme A reductase activity was observed in mevinolin treated cultures. The growth stimulatory effect of mevinolin, but not that of epithelial transforming growth factor, a polypeptide growth factor for SW13 cells, was reversed by exogenous mevalonic acid. However, neither dolichol nor low density lipoprotein supplementation affected the response of SW13 cells to mevinolin. The results suggest that mevalonic acid metabolites may participate in the regulation of anchorage independent growth of SW13 cells. PMID- 2590223 TI - Stabilization of the T-state of hemoglobin. AB - The effect of inositol hexaphosphate and bezafibrate on binding of O2 and CO to HbAO at high concentrations (1 mM) has been evaluated using thin layer optical techniques. Data analysis shows 1) the occurrence of greatly reduced ligand dependent cooperativity (Hill slope of 2.23 for CO and 1.51 for O2), and 2) the presence of significant triply ligated species. The data fits a nested allosteric two-state MWC model in which the T state consists of two allosteric substrates, Tt and Tr, where Tt binds only to the alpha chains and Tr binds to both alpha and beta chains. The model indicates that the triply ligated species consists of a predominant amount of T form, agreeing with kinetic observations of CO ligated hemoglobin. The maximum amount of triply ligated R molecules (CO or O2) implicated is less than 1%, a result similar to that found previously for binding studies made in the absence of BZF and IHP. PMID- 2590224 TI - Piceatannol (3,4,3',5'-tetrahydroxy-trans-stilbene) is a naturally occurring protein-tyrosine kinase inhibitor. AB - Piceatannol (3,4,3'5'-tetrahydroxy-trans-stilbene), a plant secondary natural product that had previously been identified as an antileukemic principle, has been shown to be an inhibitor of protein-tyrosine kinase activity. Piceatannol inhibits the purified thymocyte protein-tyrosine kinase, p40, by competing for the peptide or protein substrate binding site (Ki = 15 microM). Piceatannol also inhibits the activity of the p56lck protein-tyrosine kinase measured either in LSTRA cell membranes or in intact cells. In contrast, piceatannol does not inhibit the activity of the cAMP-dependent protein kinase. PMID- 2590225 TI - Vanadate monomers and dimers both inhibit the human prostatic acid phosphatase. AB - A combination of enzyme kinetics and 51V NMR spectroscopy was used to identify the species of vanadate that inhibits acid phosphatases. Monomeric vanadate was shown to inhibit wheat germ and potato acid phosphatases. At pH 5.5, the vanadate dimer inhibits the human prostatic acid phosphatase whereas at pH 7.0 it is the vanadate monomer that inhibits this enzyme. The pH-dependent shift in the affinity of the prostatic phosphatase for vanadate is presumably due to deprotonation of an amino acid side chain in or near the binding site resulting in a conformational change in the protein. pH may be a subtle effector of the insulin-like vanadate activity in biological systems and may explain some of the differences in selectivity observed with the protein phosphatases. PMID- 2590226 TI - Is terminal deoxynucleotidyl transferase an intracellular mutagen? AB - We have established stably transformed mammalian cell lines expressing recombinant human terminal deoxynucleotidyl transferase. A 58 kDa, enzymatically active protein is produced by these cell lines. Using the lacI gene of pJYMib shuttle vector as mutagenic target, we found no increase in mutation rates in cells expressing terminal deoxynucleotidyl transferase compared to controls. Our results suggest that the presence of terminal deoxynucleotidyl transferase alone in mammalian cells does not increase mutation rates. PMID- 2590228 TI - Pituitary follicular cells secrete both vascular endothelial growth factor and follistatin. AB - Follistatin, a hormone which acts to suppress the release of follicle-stimulating hormone (FSH) by pituitary-derived gonadotrophs, has previously been identified only in the liquor folliculi of ovarian follicles. By microsequencing of fractions derived from conditioned medium, we show here that bovine pituitary derived folliculo stellate cells are also capable of producing and secreting this hormone. These results suggest that folliculo stellate cells may serve as a source of follistatin within the pituitary itself and that the regulation of FSH release from the pituitary could therefore involve a paracrine mechanism. PMID- 2590227 TI - Enzymatic formation of nitrogen oxides from L-arginine in bovine brain cytosol. AB - In dialyzed bovine brain cytosol, the enzymatic formation of nitrogen oxides was directly determined. The basal formation of nitrite and nitrate was concentration dependently enhanced by L-arginine (EC50 about 3.10(-5) M). Both the basal and L arginine induced formations were inhibited by NG-monomethyl-L-arginine (EC50 about 2.10(-4) M). In the presence of L-arginine, a concomitant formation of citrulline was detected. L-Arginine methyl ester also served as a substrate, but neither D-arginine, D-arginine methyl ester nor N alpha-benzoyl-L-arginine ethyl ester did so. The formation of nitrite and nitrate was time-dependent, increased linearly with the protein concentration of the cytosol and was not observed when the cytosolic proteins were heat-denaturated. Exogenous NADPH (or NADP+) concentration-dependently enhanced the formation of nitrite and nitrate, whereas NADH, NAD+, FAD, Ca2+, Mg2+ and calmodulin were ineffective. These results indicate that bovine brain contains a cytosolic enzyme which uses NADPH or NADP+ as cofactors to form nitrogen oxides from both an endogenous non-dialyzable substrate and from L-arginine. PMID- 2590229 TI - A glycosylated prolactin species is covalently bound to immunoglobulin in human amniotic fluid. AB - Western immunoblots performed during separation of glycosylated prolactin from amniotic fluid revealed that some of the glycosylated prolactin is covalently bound to another protein. Using high performance liquid chromatography and other protein isolation techniques we have demonstrated that a glycosylated prolactin species is linked to immunoglobulin by disulfide bonds in amniotic fluid. PMID- 2590230 TI - Activation of the phosphorothionate insecticide parathion by rat brain in situ. AB - The ability of the rat brain to activate the phosphorothionate insecticide parathion to its potent anticholinesterase metabolite paraoxon in situ was observed by ligating the posterior portion of the circulatory system and thus removing the liver from the circulation. Under these conditions no acetylcholinesterase inhibition was observed in 15 min at a dosage of parathion (nominally 2.4 mg/kg) which yielded 95% inhibition when the liver was in the circulation. However, at a higher dose (nominally 48 mg/kg) there was substantial (about 70%) inhibition of brain acetylcholinesterase after 15 min, suggesting that the brain does have the ability to activate parathion in the intact situation. PMID- 2590231 TI - Viscometric characterization of pennisetin from pearl millet. AB - Pennisetin, the alcohol soluble storage protein of pearl millet (Pennisetum americanum), was isolated in a homogeneous state. The intrinsic viscosity [n] of this protein was found to be in the range of 16.5-17.7 ml/g in 70% (v/v) aqueous ethanol. The [eta] changed marginally when temperature was increased from 20 to 70 degrees C and also in the presence of 10 mM NaCl. The data indicated that pennisetin was a rigid, rod shaped asymmetric hydrodynamic particle with molecular dimensions in the range of 301 x 14.4 A - 317.7 x 14.2 A. During denaturation with guanidine hydrochloride (Gdn.HCl), the intrinsic viscosity of pennisetin increased from 16 to 25ml/g with a mid point at 3.6 M of the denaturant. The native protein structure was unfolded in 6 M Gdn.HCl as shown by the exposure of aromatic amino acid residues buried in the native state and this transition was found to be reversible. The intrinsic viscosity of pennisetin in 5.9 M Gdn.HCl corresponded to Mr 25,000 which was comparable to that determined by SDS-PAGE. PMID- 2590233 TI - Multiple arginine residues contribute to the increased efficacy of peptide substrates for the cAMP-dependent protein kinase. AB - Efficient cAMP-dependent protein kinase substrates typically contain an arginine dyad one amino acid removed from the residue which undergoes phosphorylation (ie. Arg-Arg-X-Ser). However, several naturally occurring protein kinase inhibitors and substrates possess additional basic residues that are proximal to the arginine dyad, implying the presence of either an extended or an additional acidic subsite on the enzyme. In this study, we investigated the substrate efficacy of several multiple arginine-bearing peptides. The most efficient substrate studied, Arg-Arg-Leu-Arg-Arg-Ala-Ser-Leu-Gly, exhibits a nearly eleven fold increase in kcat/Km relative to Leu-Arg-Arg-Ala-Ser-Leu-Gly. The enhanced kcat/Km is primarily a consequence of a reduced Km. These results suggest that a double arginine dyad, separated by a single amino acid, represents the optimal sequence for basic residues on cAMP-dependent protein kinase substrates. PMID- 2590232 TI - Lack of in vivo DNA binding of mercaptobenzothiazole to selected tissues of the rat. AB - In this study, the in vivo binding of 14C-labelled 2-mercaptobenzothiazole (MBT) to DNA was investigated. Male and female Fischer 344 rats were gavaged with 375 mg MBT/kg body weight and killed 8 hours later. DNA was extracted from the liver, adrenal glands, pituitary gland, pancreas, and bone marrow and the amount of radioactivity associated with the DNA was determined. Results from this study indicate that MBT does not significantly bind to DNA from any of the tissues examined. CBI values for liver for the 3 methods of purification were -1-3 which are on the low end of the covalent binding index. The CBI values for the other tissues were always less than 1. Other chemicals with similar CBI values include estrone and diethylstilbesterol. Strong hepatocarcinogens such as dimethylnitrosamine and aflatoxin have CBI values ranging from 6000 to greater than 20000. PMID- 2590234 TI - Response of hepatic alanine:glyoxylate aminotransferase 1 to hormone differs among mammalia. AB - The subcellular distribution and substrate specificity of hepatic alanine:glyoxylate aminotransferase 1 have been reported to differ among mammalia. In the present study, the response of this enzyme to hormone (glucagon) was found to differ among mammalia. PMID- 2590235 TI - Effects of ammonia on human neutrophil N-formyl chemotactic peptide receptor ligand interaction and cytoskeletal association. AB - Ammonia is a bacterial metabolite which is commonly used to alter cytoplasmic and lysosomal pH of eukaryotic cells. Here we examine its effect on external N-formyl peptide receptors of human neutrophils. Ammonia does not affect the number of N formyl peptide receptors on the cell surface, nor the association of the ligand receptor complex with the cytoskeleton. However, ammonia causes a marked decrease in the affinity of the chemotactic peptide receptor for its ligand. The Kd of untreated cell for the chemotactic peptide was 0.65 +/- 0.06 nM, whereas that of ammonia treated cells was 1.02 +/- 0.10 nM (Mean +/- SEM, N = 6). These results suggest that ammonia can affect external as well as internal cellular components. Since ammonia is used to alter lysosomal and cytoplasmic pH, and is a metabolite of common bacterial pathogens, these results bear directly on its use in cell biology and on its potential as a virulence factor. PMID- 2590236 TI - Intracellular [3H]dopamine binding sites in normal and malignant cells: relationships to cell proliferation. AB - Dopamine interaction with target cells undoubtably involves binding to plasma membrane receptors. However, the well documented cell growth inhibitory activity of this catecholamine suggests nuclear regulation. To evaluate this possibility, we determined the intracellular localization and binding of [3H]dopamine in human retinoblastoma (Y-79 cells), normal mouse fibroblasts (LM-cells), and in the rat uterus. Cytosol and purified nuclear preparations devoid of plasma membrane components contained specific, saturable, high affinity (Kd approximately 20 nM) binding sites for [3H]dopamine. The nuclear binding affinity for dopamine, L dopa, and L-dopa methyl ester correlated with the inhibitory effects of these compounds on cell proliferation, suggesting that intracellular dopamine binding sites may also be involved in cellular response to catecholamines. PMID- 2590237 TI - Increased therapeutic efficacy of zidovudine in combination with vitamin E. AB - Antiviral activity and bone marrow toxicity of 3'-azido-3'deoxythymidine (Zidovudine; AZT) was evaluated in the presence of alpha-D-tocopherol acid succinate (ATS) in the MT4 cell line and in murine hematopoietic progenitor cells, respectively. At varying concentrations (.016 to .125 microM) of AZT, addition of ATS (5 to 15 micrograms/ml) showed a dose-dependent increase in anti HIV activity. The ED90 of AZT in this test system was 0.37 microM, whereas in the presence of ATS (15 micrograms/ml) it was 0.06 microM, thus producing an approximately 6-fold increase in anti-HIV activity. In contrast, in murine bone marrow cells, ATS (4 micrograms/ml) showed significant protection (p less than 0.05) against AZT-induced toxicity as measured by CFU-E and CFU-GM assays. The IC50 values in the presence and absence of ATS for CFU-E were 3.7 and 1.5 microM, whereas for CFU-GM were 6.0 and 2.7 microM, respectively. Overall, these data suggest that AZT in combination with ATS has greater therapeutic efficacy against HIV-1. PMID- 2590238 TI - Possible involvement of actomyosin ADP complex in regulation of Ca2+ sensitivity in alpha-toxin permeabilized smooth muscle. AB - The effects of substrate condition and ADP beta S on the pCa2+-tension relationships were investigated, using alpha-toxin permeabilized rabbit mesenteric artery at 37 degrees C. The contraction induced by 10 microM Ca2+ solution after permeabilization was as large as that induced by 145 mM K+ PSS solution containing 10 microM NE in the intact tissue, indicating that the majority of the cells were permeabilized. The Ca2+ sensitivity was greatly affected by the substrate condition and increasing the ratio of ATP/CP induced a leftward shift of the pCa2+-tension curve. Addition of 100 microM ADP beta S had a similar effect. When the ATP/CP ratio was high, the 0.1 microM Ca2+ solution relaxed the tissue precontracted by 10 microM Ca2+ solution more slowly showing hysteresis. One mM vanadate, which is reported to relax muscle by forming actomyosin-ADP-Vi (AM-ADP-Vi), completely inhibited both contractions induced by 0.18 microM Ca2+ solution containing 2 mM MgADP and 0.3 microM Ca2+ solution containing 0.3 microM PDBu. These results indicated that the population of AM-ADP complex in the crossbridge had increased due to the accumulation of ADP inside the tissue or activation of PKC and that the inhibition of ADP release from AM ADP complex may be playing a key role in increasing Ca2+ sensitivity of myofilaments. PMID- 2590239 TI - Dimethylated arsenics induce DNA strand breaks in lung via the production of active oxygen in mice. AB - In order to study the genotoxicity of arsenics, we focused our attention on dimethylarsinic acid (DMAA) which was a main metabolite of inorganic arsenics in mammals. ICR mice were orally administered DMAA-Na (1500mg/kg). DNA single-strand breaks occurred specifically in lung at 12h after administration. An in vitro experiment indicated that the breaks were not caused directly by DMAA but by dimethylarsine, a further metabolite of DMAA. Furthermore, the dimethylarsine induced breaks were diminished by the addition of SOD and catalase, suggesting that active oxygen produced by dimethylarsine was involved in the induction of DNA damage. PMID- 2590240 TI - Regulation of cytochrome P-450 dependent steroid hydroxylase activity in Manduca sexta: evidence for the involvement of a neuroendocrine-endocrine axis during larval-pupal development. AB - Ecdysone 20-monooxygenase activity and the factors which may regulate this steroid hydroxylase were examined in the midgut of the tobacco hornworm, Manduca sexta, during the last larval stadium. Radioassay experiments revealed that midgut ecdysone 20-monooxygenase undergoes a single 50-fold increase in activity temporally coincident with the onset of the wandering stage. The increase in midgut monooxygenase activity was prevented by actinomycin D and cycloheximide, and could be elicited in head (but not thoracic) ligated animals by a brain retrocerebral complex factor(s) released at the same time as prothoracicotropic hormone. In contrast, ecdysone or 20-hydroxyecdysone could elicit the increase in enzyme activity in both head and thoracic ligated animals. These data suggest the operation of a neuroendocrine-endocrine axis in the regulation of midgut ecdysone 20-monooxygenase activity. PMID- 2590241 TI - Thyrotropin stimulates transcription from the ferritin heavy chain promoter. AB - Thyrotropin (TSH) is the primary hormone regulating the activity of the thyroid gland. We have recently shown that TSH stimulates H-ferritin mRNA levels in rat thyroid. Ferritin plays a key role in determining the intracellular fate of iron. The induction of ferritin synthesis by iron in liver is regulated both at transcriptional and translational levels. Here we present evidence that the mechanisms by which TSH regulates the mRNA levels are mediated by a diffusible product acting in trans on its own promoter. In fact, the H-ferritin promoter mediates increased CAT activity in response to hormone induction. Our results identify transcription as an important regulatory step of TSH action. They suggest that TSH induces expression of the ferritin gene, and that continuous protein synthesis is required to maintain basal ferritin gene expression in the absence of hormone. PMID- 2590242 TI - Cell type-specific expression of the genes for the protein kinase C family: down regulation of mRNAs for PKC alpha and nPKC epsilon upon in vitro differentiation of a mouse neuroblastoma cell line neuro 2a. AB - By the use of cloned cDNAs for protein kinase C isozymes alpha, beta I, beta II, gamma, and those for novel protein kinase C, epsilon and zeta, the expression of the corresponding mRNA species was examined in various mouse tissues, human lymphoid cell lines, and mouse cell lines of neuronal origin. In adult brain, mRNAs for all the isozymes of PKC family are expressed. However, the expression of these mRNA species in brain is low at birth. A similar pattern of expression was also observed for beta I/beta II mRNAs in spleen. These expression patterns are in clear contrast to that for beta I/beta II mRNAs in thymus where the mRNAs are expressed at birth and the levels of expression decrease with age. Human lymphoid cell lines express large amounts of PKC beta mRNAs in addition to PKC alpha. Further, nPKC epsilon mRNA is expressed in some of these cell lines. On the other hand, all the mouse cell lines of neuronal origin tested express nPKC epsilon and zeta in addition to PKC alpha. In a mouse neuroblast cell line, Neuro 2a, down modulation of mRNAs for both PKC alpha and nPKC epsilon was observed in association with in vitro differentiation. PMID- 2590243 TI - Effects of okadaic acid on mouse hemopoietic cells. AB - Effects of okadaic acid, a potent non-12-O-tetradecanoyl-phorbol-13-acetate(TPA) type tumor promoter, on mouse hemopoietic cells were investigated. Okadaic acid stimulated mouse bone marrow cells to form granulocyte-macrophage colony-forming unit (CFU-GM) colonies without added colony stimulating factors(CSFs). At the concentration of 1.82 x 10(-8) M, colony formation of 77 +/- 14 colonies/1 x 10(5) bone marrow cells was observed. Observations on the effects of other cells on the CSF induction suggested that okadaic acid primarily stimulated the functions of macrophages, and the CSF production from macrophages might be attributed to the CFU-GM colony formation. On the other hand, the erythroid colony-forming unit(CFU-E) colony formation stimulated by PMID- 2590244 TI - The membrane potential changes polarity during capacitation of murine epididymal sperm. AB - The membrane potential in murine epididymal sperm was determined with a voltage sensitive, fluorescent probe. In freshly collected sperm, the potential was inside-negative, viz., -13 mV, and was associated with an intracellular K+ concentration of about 122 mM. Following incubation of sperm in a medium capable of sustaining capacitation and fertilization efficacy, the potential became gradually positive. An inside-positive potential, +24 mV, was obtained after 40 min of incubation, concomitant with an intracellular K+ concentration of approximately 30 mM. At this time, about 70 percent of sperm had capacitated. An inside-positive membrane potential may play a role in facilitating the acrosome reaction. PMID- 2590245 TI - Characterization of the high pH wobble structure of the 2-aminopurine.cytosine mismatch by N-15 NMR spectroscopy. AB - Transition mutations induced by the base analogue 2-aminopurine arise via the formation of AP.C base pairs during DNA replication. We report here the results of N-15 NMR studies on a duplex oligonucleotide containing N-15 enriched AP and C residues. At high pH (8.6) the AP.C base pair is predominantly wobble. This is the first report on use of a site specifically N-15 enriched oligonucleotide as a probe of aberrant base pairing in DNA. PMID- 2590246 TI - [High performance liquid chromatography of peptide bioregulators, their fragments and derivatives. III. Regularities of sorption, prediction of retention and analysis of peptides by a reversed phase HPLC method]. AB - Parameters of statistical models of fully or partially protected peptides' retention on Zorbax ODS and Silasorb C18 have been compared. The proposed model can be used for non-protected linear and cyclic peptides. Special increments have to be introduced in calculation of hydrophobicity of these peptides. PMID- 2590247 TI - [Microcolumn exclusion HPLC of globular proteins with refractive index detection]. AB - A method of determination of molecular masses of globular proteins based on microcolumn size-exclusion HPLC on modified silica sorbent (TSK-GEL 3000 SW) with refractometric detection has been developed. Molecular masses in the range 10 to 200 kD were determined with the accuracy of +/- 3%. PMID- 2590248 TI - [The effect of anions on spectral properties of iodopsin and native cones in the frog retina (microspectrophotometric study)]. AB - Absorption spectra of single outer segments of the frog Rana temporaria photoreceptors were registered. Effects of nitrate and chloride ions on spectral properties of cone and rod pigments were compared. These pigments proved to differ in structure of the native photoreceptor membrane and, therefore, in effect of hydrophile environment on the chromophore centrum. Substitution of chloride by nitrate ions led to the hypochromic shift of the cone absorption spectrum (20-25 nm) but does not affect the spectrum on case of rod pigment. The ionochromic behaviour of cone pigments resembles that of the light-sensitive halobacterium protein halorhodopsin, in native membrane. We suppose that the effect of anions on the chromophore centrum may be the cause of bathochromic shifts of absorption spectra of longwave-length retinal-containing pigments. PMID- 2590249 TI - [A study of the interaction of substrates with cytochrome P-450 by a method of UV and 1H-NMR spectroscopy]. AB - Acceleration of substrate longitudinal relaxation (T1) was used to study cytochrome P-450-aminopyrine (1st type substrate) and P-450-4-methoxypyridine (2nd type substrate) complexes. Dissociation constant, T1 and/or residence time of substrate in the complex can be obtained from the dependence of T1 of substrate protons on substrate concentration. Basing on the relaxation times, distances between Fe3+ ion in the active site and protons of the substrate moiety were determined. For aminopyrine all the distances proved to be about 8 A. In the P-450-4-methoxypyridine complex the pyridine nitrogen is directed towards Fe3+ ion. Cytochrome P-450 is compared with its denatured form, cytochrome P-420, and metmyoglobin. PMID- 2590250 TI - [Obtaining unidirectional deletions in a plasmid using a DNA-"protector" and Bal31 exonuclease]. AB - A method of generating unidirectional deletions from the cleavage site of any endonuclease by means of exonuclease Bal31 is developed. DNA sequence to be prevented from Bal31 hydrolysis is protected by a special "protector" element TH (Trojan Horse) inserted upstream of the sequence. PMID- 2590251 TI - [High performance liquid chromatography of peptide bioregulators, their fragments and derivatives. IV. Chromatographic behavior and purification of oxytocin]. AB - Chromatographic behaviour of oxytocin has been studied. A simple and convenient technique has been developed for preparative purification of oxytocin using silica and ethanol. The product obtained contains not more than 3% impurities and has activity about 450 IU/mg. PMID- 2590252 TI - [Conformation-activity relations of des-Arg9-bradykinin. I. Conformation of molecules in solution]. AB - The spatial structure of [des-Arg9]bradykinin, a selective agonist of the B1 type kinin receptors, was studied by means of theoretical conformational analysis. In order to restrict the number of conformations under consideration, we used available data on 1H NMR in (CD3)2SO solution indicating the C-terminal carboxyl group to interact with the guanidine group of Arg1 and the hydroxyl group of Ser6. The calculated set of [des-Arg9]bradykinin low-energy conformations was compared with the 1H NMR data. Four types of conformations were selected, which are consistent with experimental data and serve as sterically reliable models for the preferable three-dimensional structure of [des-Arg9]bradykinin in solution. PMID- 2590253 TI - [Active derivatives of oligonucleotides with a zwitterionic terminal phosphate group for design of affinity reagents and probes]. AB - Method of synthesis and isolation of oligonucleotide derivatives with a zwitterionic terminal phosphate group, containing N-methylimidazole (MeIm), 4 dimethylaminopyridine (DMAP) or 4-dimethylaminopyridine 1-oxide (DMAPO) residues has been developed. Mononucleotide derivatives were used to study the reactivity of these compounds to various nucleophiles and the dependence of hydrolysis rate on pH of solution. These compounds interact rapidly and quantitatively with aliphatic amines and much slower with water, aniline and methanol. MeIm derivatives are most active to nucleophiles, whereas the reactivity of DMAP derivatives is ca. 5 times lower and that of DMAPO derivatives is lower by 2 order of magnitude. This method of activating terminal phosphate group is promising for synthesis of various oligonucleotide phosphoramidates. PMID- 2590254 TI - [Synthesis and antioxidative activity of structural analogs of vitamin E]. AB - Analogues of alpha-tocopherol with modified structure of side isoprenoid chain and chroman nucleus have been synthesised. The influence of chromanol structure on the dynamic of oxidation products formation have been investigated on models of induced and noninduced bulk-phase peroxidation of ethyl linoleate in presence of 2.3.10(-3)-1.2.10(-2) M alpha-tocopherol and the synthesised compounds. PMID- 2590255 TI - [Preparation and properties of prostaglandin D2 labelled with tritium with high molar radioactivity]. AB - Kinetic parameters of enzymatic and non-enzymatic transformations of [3H]prostaglandin H2 (PGH2) were determined; the maximum yield of [3H]PGD2 being obtained at the keobs/koobs ratio equal to 10. The two-stage enzymatic synthesis of [3H]PGD2 with high molar radioactivity (3.15 TBq/mmol) from [3H]arachidonic acid carried out. Its identity in properties to the natural PGD2 was shown in experiments on the inhibition of ADP-induced aggregation of thrombocytes and on enzymatic oxidation with 15-hydroxyprostaglandin dehydrogenase. PMID- 2590256 TI - [Isolation of alpha-latrotoxin from karakurt spider venom using monoclonal antibodies]. AB - A method of alpha-latrotoxin (LT) isolation from the venom of Latrodectus mactans tredecimguttatus by means of immunoaffinity chromatography on sepharose conjugated with monoclonal antibodies against LT has been developed. This one step, high-yield, relatively simple and rapid procedure yields active LT for structural and functional studies of its receptor. PMID- 2590257 TI - Immunomodulation by the new synthetic thiazole derivative tiprotimod. 2nd communication: immunopharmacological activity. AB - The thiazole derivative [2-(3-carboxy-1-propylthio)-4-methyl-1,3-thiazole] acetic acid (tiprotimod, HBW 538) a new synthetic immunopotentiator of low molecular weight, has been tested in vivo and ex vivo in various experimental models. Its influence on parameters of macrophage functions, on DTH (delayed type hypersensitivity)-reaction and antibodies to sheep erythrocytes (SRBC), Tetanus toxoid and heatkilled E. coli bacteria in mice, and in the popliteal lymph node assay in rats was investigated. When mice were treated with the test substance i.v., i.p., or p.o. in a dose range from 1-100 mg/kg, a time and dose-dependent stimulation of macrophage activity was observed. The drug was able to enhance the DTH-response against SRBC and to stimulate the humoral immune response against Tetanus toxoid and heat-killed E. coli. In the popliteal lymph node assay, a murine graft-vs-host model, a stimulating effect of the substance was observed when it was administered at the same time of the grafts to rats. These results demonstrate that tiprotimod is a potent immunopotentiator for both humoral and cell mediated immune response in experimental animals. PMID- 2590258 TI - Antioxidant activity of probucol. Short communication. AB - To evaluate a possible antioxidant activity of probucol on NADPH-dependent microsomal lipid peroxidation and on iron-doxorubicin (adriamycin) complex induced phospholipid peroxidation, the effects were compared with another powerful antioxidant, 2-OH-estrone. Antioxidant activity of 10 mumol/l probucol in NADPH-dependent microsomal lipid peroxidation corresponded to 4 mumol/l 2-OH estrone. Together with the results obtained from iron-doxorubicin complex-induced phospholipid peroxidation, it was concluded that probucol is a potent inhibitor of lipid peroxidation and has one-quarter to one-half the antioxidant activity of 2-OH-estrone in vitro. PMID- 2590259 TI - Metabolic fate of the new Ca++-channel blocking agent (+)-(2S,3S)-3-acetoxy-8 chloro-(2-(dimethylamino)ethyl)-2,3-dihydro- 2-(4-methoxyphenyl)-2,5 benzothiazepin-4-(5H)-one maleate. Distribution, excretion and protein binding in rats and dogs. AB - Distribution, excretion and protein binding of (+)-(2S,3S)-3-acetoxy-8-chloro-(2 (dimethylamino)ethyl)-2,3-dihydro- 2-(4-methoxyphenyl)-2,5-benzothiazepin-4-(5H) one maleate (TA-3090) in rats and dogs were investigated after oral (30 mg/kg (rats), 2 mg/kg(dogs] and intravenous (3 mg/kg (rats), 0.2 mg/kg (dogs) administration of 14C-TA-3090. Plasma level of radioactivity in rats reached plateau (6.04 micrograms equiv. of TA-3090 free base/ml) 1 h after oral administration. The plateau level continued at least up to 6 h. The plasma concentration of the unchanged drug (free base) reached the maximum (425 ng/ml) at 45 min after oral administration, and then decreased with a half-life of 1.16 h. Plasma level of radioactivity after intravenous administration to rats rose gradually up to 1 h and thereafter it was kept constant for 6 h. Plasma concentration of the unchanged drug decreased with half-lives of 0.43 h (alpha phase) and 1.33 h (beta phase) after intravenous administration. In dogs, the peak level of plasma radioactivity after oral administration was 227 ng/ml at 1 h. The Cmax, Tmax and t1/2 of unchanged drug were 31 ng/ml, 1.34 h and 4.13 h, respectively. The plasma levels of total radioactivity and unchanged drug after intravenous administration to dogs were 146 and 142 ng/ml at 1 min, respectively. The t1/2 of the plasma radioactivity were 0.02 h (alpha) and 4.02 h (beta). Those of unchanged drug were 0.03 h (alpha) and 1.66 h (beta).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590260 TI - Antispasmodic activity of tiropramide. AB - Tiropramide hydrochloride and some of its metabolites were studied in vivo for their antispasmodic activities on the following models: gastric emptying in the mouse retarded by cholecystokinin octapeptide (CCK-8) or morphine, progression of intestinal contents in the mouse, spontaneous motility of the colon in the anesthetized rabbit, diarrhea induced by castor oil in the rat, spasm of the sphincter of Oddi provoked by morphine in the guinea pig, contractions of the urinary bladder in the anesthetized rat. On these models tiropramide had an antispasmodic activity at doses of 4-40 mg/kg i.p. or i.v. and of 50-90 mg/kg orally. The potency was greater on "pathological" contractions or spasms and smaller on "physiological" movements. Tiropramide may therefore be regarded as a "eukinetic" antispasmodic agent. Tiropramide in general was more potent than reference agents such as papaverine or flavoxate and was active also after oral administration. The metabolites of tiropramide, i.e. CR 1034, CR 1098 and CR 1166 showed similar pharmacodynamic effects, but their potency was smaller than that of tiropramide. Large doses of tiropramide have depressive actions on the cardiovascular system, which can be seen especially if tiropramide is administered i.v. and are less pronounced after oral administration. The circulatory effects are therefore probably the limiting factor for increasing the parenteral doses of tiropramide in human therapy. Tiropramide was found less toxic than papaverine (LD50). The metabolites of tiropramide were less toxic than the parent compound. The toxicity of the chiralic forms of tiropramide does not differ significantly from that of the racemic substance. PMID- 2590261 TI - Pharmacological characterisation of the smooth muscle antispasmodic agent tiropramide. AB - (+/-) Tiropramide hydrochloride, its D and L optical isomers and some of its metabolites were characterized in a number of in vitro pharmacological tests. Tiropramide showed broad spectrum antispasmodic activities on the isolated stomach of guinea pig electrically stimulated; on the longitudinal muscles of the ileum of guinea pig stimulated by electrical impulses, BaCl2, acetylcholine, histamine, serotonin, substance P and cholecystokinin octapeptide (CCK-8); on the spontaneous contractions and on the electrical inhibition of the jejunum of rabbit; on the spontaneous contractions and on the contractions provoked by BaCl2 and acetylcholine of the ascending colon of the rat; on the contractions provoked by BaCl2, acetylcholine, histamine and cerulein of the circular muscles of the gall bladder of the guinea pig; on the spontaneous contractions of the pyel ureter preparation of the guinea pig; on the contractions of the uterus of the rat provoked by oxitocin, serotonin, acetylcholine, PGF2; on the spontaneous contraction of the portal vein of the rat; on the constriction of the tail artery of the rat provoked by electrical stimulation, epinephrine and ergotamine; on the contractions of the aortic strip of the rabbit stimulated by norepinephrine; on the contractions of the strip of bovine coronary artery depolarized by HCl. In general tiropramide had antispasmodic effect at 5-60 mumol/l concentration. It was more potent than papaverine on contractions provoked by electrical or chemical stimuli, and was less potent or ineffective on spontaneous and "physiological" contractions of the different smooth muscle preparations. Tiropramide had small effects on vascular smooth muscles and showed very small calcium channel blocking activity. PMID- 2590262 TI - Investigation on the effect of dipyridamole and papaverine on regional blood flow and cardiac hemodynamics in anesthetized dogs. AB - Vasodilating effects of dipyridamole were compared with those of papaverine in anesthetized open-chest dogs. Dipyridamole i.v. produced a significant fall in aortic blood pressure and significant increases in aortic and coronary blood flows. Vertebral blood flow did not alter, but renal blood flow was transiently decreased. Left ventricular dP/dt, heart rate and left ventricular enddiastolic pressure were hardly affected by dipyridamole. Papaverine i.v. significantly increased aortic, vertebral and coronary blood flows, left ventricular dP/dt and heart rate and significantly decreased aortic blood pressure and left ventricular enddiastolic pressure. Renal blood flow was instantly decreased by papaverine. Percent change in each vascular resistance showed decreases in total peripheral, vertebral and coronary vascular resistances in response to both drugs, and the decrease in coronary vascular resistance was the most remarkable. Renal vascular resistance was increased by dipyridamole, while it was decreased by papaverine. Percent change in double product (heart rate x systolic arterial blood pressure) showed a monophasic decrease pattern with dipyridamole and a biphasic pattern with an initial, transient decrease followed by an increase with papaverine. The present results indicate that dipyridamole and papaverine produce marked coronary vasodilatation, and that papaverine is different from dipyridamole in cardiotonic properties. PMID- 2590263 TI - Electrophysiologic, haemodynamic and antiarrhythmic effects of the new class Ic agent 1-(2'-biphenyloxy)-2-tert.-butylamino-propanol-2-hydrochloride. AB - The electrophysiological, antiarrhythmic and haemodynamic profile of the new compound GK 23-G (1-(2'-biphenyloxy)-2-tert.-butylamino-propanol-2-hydrochloride, proposed INN: bipranol) was examined using dogs models relevant to conditions in humans. In the first part of the study, dose-related effects of cumulatively increasing doses of GK 23-G (0.2-12.8 mg/kg) on intracardiac conduction, ventricular refractoriness and on haemodynamic parameters of the non-ischemic heart were determined in six anesthetized mongrel dogs. In the second part of the study, antiarrhythmic actions of bipranol on "delayed reperfusion ventricular arrhythmias" following release of coronary artery occlusion after 2 h of obstruction were investigated in another six dogs. The results show: GK 23-G causes a significant prolongation of HV-time, QRS-duration and ventricular refractory period at mid-range and high doses (greater than or equal to 3.2 mg/kg). QT-time does not change. Atrial refractory period is significantly lengthened at the maximum dose of 12.8 mg/kg. There are no significant changes in heart rate, systolic and diastolic aortic pressure and cardiac output. Up to 12.8 mg/kg, GK 23-G does not influence left ventricular contractility (dp/dtmax). In acute myocardial necrosis "delayed reperfusion arrhythmias" are almost completely abolished at a dose of 1.6 mg/kg + 50 micrograms/kg x min. Thus, because of its antiarrhythmic potency, further experimental and clinical testing of the new compound seems promising. PMID- 2590264 TI - Bioavailability of trapidil tablets. AB - Trapidil was given orally (200 mg, Rocornal dragees 100 mg) and intravenously (100 mg) to 12 healthy volunteers. Serum samples were analyzed for trapidil by HPLC. Complete bioavailability was obtained and a mean absorption time of 66.4 min was calculated using the method of curve moments. PMID- 2590265 TI - Pharmacokinetic and pharmacodynamic interactions between single oral doses of ibopamine and food in normal man. AB - The pharmacokinetic and pharmacodynamic interactions between single oral doses of 200 mg ibopamine and a standard cold 3100 kJ meal were assessed in 12 normal male subjects, who were studied on 4 occasions, receiving either ibopamine or matched placebo (double-blind) in fasting condition or at the end of a meal. Treatments were randomly allocated in a period-balanced within-subject cross-over study design. The plasma concentrations of epinine (N-methyldopamine) were extensively profiled up to 4 h after dosing. Food caused a profound reduction of both Cmax and AUC of unconjugated epinine with a prolongation of Tmax. The subjects were furthermore profiled in detail up to 4 h after dosing by transthoracic impedance cardiography. Food caused substantial and protracted effects that affected virtually all parameters profiled. Ibopamine had clear cardiac performance enhancing effects only over the first hour after dosing. These effects were furthermore subject to significant food interaction. It therefore appeared that food resulted in a profound blunting of both ibopamine's pharmacokinetic and pharmacodynamic characteristics. PMID- 2590266 TI - [Proof of bioequivalence of two nifedipine preparations]. AB - A crossover-study was performed with 20 volunteers in order to demonstrate the bioequivalence of two nifedipine preparations after single dose application. Methods for demonstrating bioequivalence were according to the APV (Arbeitsgemeinschaft fur pharmazeutische Verfahrenstechnik)- and FDA-guidelines; in addition some new but less well-known biometric procedures were used. Bioequivalence could be proved for the criteria AUC, Cmax and tmax as stated in the nifedipine monograph of Zentrallaboratorium Deutscher Apotheker. PMID- 2590267 TI - Pharmacokinetics of once-daily theophylline dose following the morning versus evening administration. AB - The pharmacokinetics of theophylline (Uniphyllin) in blood and saliva was compared after morning and evening administration of a once-daily dose in a randomized cross-over study. Ten bronchial asthma patients received multiple doses of 800 mg theophylline at 8 a.m. and 8 p.m. under controlled food conditions. The precision of the serum concentration prediction from salivary measurements in individual patients was sufficient to obtain identical pharmacokinetic parameters and parallel concentration-time curves. There were no significant differences in the values of mean residence time and area under the concentration-time curves after morning and evening dosing, either in the kinetics of elimination and in the volume of distribution. The fluctuation of concentrations during the dosing intervals was 100% after morning doses and 80% after evening doses. No consistent interference with food was found. Circadian variation in the kinetics of drug disposition after once-daily theophylline administration did not occur. In order to achieve higher therapeutical levels at night and in the morning, the evening dosing seems to be preferable. PMID- 2590268 TI - [Hemostasis disturbance caused by cephalosporins with an N-methylthiotetrazole side chain. A randomized pilot study]. AB - The mechanism of hypoprothrombinemia induced by cephalosporins containing the N methylthiotetrazole (NMTT) side chain has been investigated in a randomized clinical, trial (pilot study) with 14 hospitalized patients (main inclusion criteria: age greater than or equal to 50 years, urinary tract infection, normal prothrombin time. Therapy groups: latamoxef (n = 5), cefoperazone (n = 5), cefotaxime (control, n = 4). Duration of treatment: 7 days). Two patients under cefoperazone exhibited a significant increase of prothrombin time, accompanied by the appearance of PIVKA II (prothrombin induced in vitamin K absence). Both cefoperazone (in 4 patients) and latamoxef (in 3 patients) caused the appearance of endogenous vitamin K1 2,3-epoxide, whereas cefotaxime did not. This confirms the hypothesis that NMTT-cephalosporins are inhibitors of hepatic vitamin K epoxide reductase, and that this is at least partly responsible for the clinically observed hypoprothrombinemia. In older patients treated with these antibiotics, prothrombin time should be controlled before as well as under therapy. Unexpectedly, the patients displaying an appearance of vitamin K1 2,3 epoxide showed a statistically significant increase of endogenous plasma vitamin K levels. This effect needs further investigation. PMID- 2590269 TI - [Bioequivalence of an optimized doxycycline preparation]. AB - The galenically optimized and pharmaceutically balanced doxycycline preparation Sigadoxin was compared with a reference preparation according to the new "Criteria for testing of the bioavailability and bioequivalence of doxycycline containing products" recommended by the Central Laboratory of German Pharmacists. The statistical evaluation of the AUC and Cmax of the trial preparations and the urinary excretion rates from commercial production batches, which were of good quality in accordance with the present state of pharmaceutical knowledge, showed the comparable bioavailability of the two preparations, which can thus be considered as bioequivalent. The AUC and Cmax for the trial preparation were 44.9 mg/l and 2.87 mg/l, respectively. For the reference preparation the values for these parameters were 50.3 mg/l and 3.19 mg/l, respectively. The relative bioavailability, based on the AUC, was 89.3%. PMID- 2590270 TI - [Concentrations of ibuprofen and the protein and pH value of synovial fluid and plasma following oral administration of ibuprofen in patients with arthritis]. AB - Concentrations of Ibuprofen and Protein Concentration and pH-Value in Synovial Fluid and Plasma Following Oral Administration of Ibuprofen in Patients Suffering from Arthritis. In 16 patients suffering from arthritis of the knee the concentration of ibuprofen in the synovial fluid was examined in correlation with the synovial fluid volume, cell count, pH value and protein concentration. The mean ibuprofen concentration in plasma 4 h after oral administration of 400 mg ibuprofen amounted to 15.45 micrograms/ml, the concentration in the synovial fluid was 9.4 micrograms/ml. Due to the inflammatory nature of the effusions the protein concentration in the synovial fluid was evidently increased to an average of 4.46 g/dl and thus was about 65% of the mean plasma protein concentration of 6.88 g/dl. The ibuprofen in the synovial fluid showed a correlation to the protein concentration. On the other hand, there were no significant differences between the pH value in the plasma and in the synovial fluid. There was no tendency to an acid pH. Furthermore, there was no correlation between ibuprofen concentration and cell count. The tests showed that the "accumulation" of the nonsteroidal antiinflammatory drug in the synovial fluid is positively correlated with the high protein concentration but not with the pH value. PMID- 2590271 TI - [Protective effect of an antacid against acetylsalicylic acid]. AB - The protective action of an magnesium-aluminum-antacid (Mucal-Gel) against acute doses of acetylsalicylic acid (ASA) was studied in healthy subjects (n = 30) by a double-blind cross-over method. The severity of the lesion was determined by endoscopy. In the corresponding placebo experiments, severe lesions of the gastroduodenal mucosa were seen after administration of 1500 mg ASA. These lesions could be prevented only in the presence of high doses of the antacidum mixture. It is concluded from these studies that protective actions against ASA can be achieved only if the intragastric pH-level is adequately raised above 3.5 and higher. PMID- 2590272 TI - [The effect on wound healing of venous leg ulcers of a two-layered polyurethane foam wound dressing]. AB - To demonstrate the effect of a two-layered polyurethane foam wound dressing (Lyomousse) on the healing of venous leg ulcers a comparative study in 41 patients (24 treated, 17 controls) was performed. For a quantification of the process of healing a computer-assisted morphometric procedure was used. This method is based on a Polaroid-photograph of the ulceration which is transferred in digital form by means of a digitizing equipment. From the digital data the primary variables area, perimeter and maximal diameter of the ulceration are calculated. For quantitative comparison the relative changes as well as the rate of the changes of the primary variables were used. The statistical comparison of the treated group and the control group showed a highly significant (p less than 0.001) promotion of wound healing for the therapy with the synthetic foam dressing using the relative changes as an indicator, and a significant (p less than 0.05) increase in the rates of changes, indicating an acceleration of healing. This therapeutical advantage can be drawn back to specific characteristics of the synthetic material, assuring a water vapour saturated micro-environment at the surface of the wound and reducing this way the detrimental effect of heat loss due to evaporation onto the healing process. PMID- 2590273 TI - Pharmacokinetics of tumor necrosis factor alpha after intravenous administration in rats. Dose dependence and influence of tumor necrosis factor beta. AB - 2, 10, 20, 100 and 500 micrograms/kg/0.5 h of recombinant human tumor necrosis factor alpha (TNF-alpha) were administered to rats by intravenous infusion over 30 min. At high doses (greater than 10 micrograms/kg/0.5 h) the plasma half-life (t1/2, about 0.5 h) of TNF-alpha was practically dose independent. In contrast at the lowest dose (2 micrograms/kg/0.5 h) the elimination of TNF-alpha was markedly faster: A plasma half-life of only 5-8 min was determined. However, when in addition to 2 micrograms/kg/0.5 h of TNF-alpha a high dose of recombinant human tumor necrosis factor beta (TNF-beta) was infused the plasma half-life was enhanced up to values at high doses (greater than 10 micrograms/kg/0.5 h). Thus at the lowest dose the speed of elimination of TNF-alpha was enhanced which could be prevented by TNF-beta. PMID- 2590274 TI - Trends shaping U.S. society 1990-2005. PMID- 2590275 TI - Stick to humans. PMID- 2590276 TI - Ankinomycin, a potent antitumor antibiotic. PMID- 2590277 TI - Synthesis, DNA-binding properties, and antitumor activity of novel distamycin derivatives. AB - A group of potential alkylating agents have been synthesized that are structurally related to the oligopeptide antiviral antibiotic distamycin. All derivatives form complexes with native calf-thymus DNA but compounds 2, 3, and 6 give rise to covalent adducts. Cytostatic activity against both human and murine tumor cell lines in vitro is displayed by the new compounds. Compounds 3 and 4 are active on melphalan-resistant L1210 leukemia in mice. PMID- 2590278 TI - Binaural disparity cues available to the barn owl for sound localization. AB - 1. Bilateral recording of cochlear potentials was used to measure the variations in interaural time differences (ITDs) and interaural intensity differences (IIDs) as a free-field auditory stimulus was moved to different positions around a barn owl's head. 2. ITD varied smoothly with stimulus azimuth across a broad frequency range. 3. ITD varied minimally with stimulus elevation, except at extreme angles from the horizontal. 4. IID varied with both stimulus elevation and stimulus azimuth. Lower frequencies were more sensitive to variations in azimuth, whereas higher frequencies were more sensitive to variations in elevation. 5. The loci of spatial coordinates that form iso-IID contours and iso-ITD contours form a non orthogonal grid that relates binaural disparity cues to sound location. PMID- 2590279 TI - "Teleauscultation": the next best thing to being there. PMID- 2590280 TI - Food hygiene in the 1990s. PMID- 2590281 TI - 'Patient safety in general anaesthesia'. PMID- 2590282 TI - Radioisotope penile plethysmography: a technique for evaluating corpora cavernosal blood flow during early tumescence. AB - Radioisotope penile plethysmography is a nuclear medicine technique which assists in the evaluation of patients with erectile dysfunction. This technique attempts to noninvasively quantitate penile corpora cavernosal blood flow during early penile tumescence using technetium-99m-labeled red blood cells. Penile images and counts were acquired in a steady-state blood-pool phase prior to and after the administration of intracorporal papaverine. Penile counts, images, and time activity curves were computer analyzed in order to determine peak corporal flow and volume changes. Peak corporal flow rates were compared to arterial integrity (determined by angiography) and venosinusoidal corporal leak (determined by cavernosometry). Peak corporal flow correlated well with arterial integrity (r = 0.91) but did not correlate with venosinusoidal leak parameters (r = 0.01). This report focuses on the methodology and the assumptions which form the foundation of this technique. The strong correlation of peak corporal flow and angiography suggests that radioisotope penile plethysmography could prove useful in the evaluation of arterial inflow disorders in patients with erectile dysfunction. PMID- 2590283 TI - Re: "Causality inference in observational vs. experimental studies: an empirical comparison". PMID- 2590284 TI - Nursing care of a terminally ill client. Applying Martha Rogers' conceptual framework. PMID- 2590285 TI - Celiac sprue: another endoscopic view. PMID- 2590286 TI - Wrestler's hematoma. PMID- 2590287 TI - Formyl-methionyl-leucyl-phenylalanine-induced intestinal inflammation. PMID- 2590288 TI - Taurine and other dietary considerations for cats. PMID- 2590289 TI - Magnetic resonance imaging of normal and pathological white matter maturation. PMID- 2590290 TI - Diagnosis of a fourth reported case of intestinal anisakiasis in the United States? PMID- 2590291 TI - Additional criteria for sample division suggested. PMID- 2590292 TI - More on cleft lip and palate patient. PMID- 2590293 TI - A pitfall in the xanthine oxidase hypothesis. PMID- 2590294 TI - Acute visual and auditory neurotoxicity in patients with end-stage renal disease receiving desferrioxamine. PMID- 2590295 TI - DNA flow cytometry in the prognosis of node-negative breast cancer. PMID- 2590296 TI - The physician factor in cesarean birth rates. PMID- 2590297 TI - Cerebellar peduncular hemorrhage. PMID- 2590298 TI - Paediatric fees. PMID- 2590299 TI - The acute effect of cordocentesis with or without fetal curarization and of intravascular transfusion upon umbilical artery waveform indices. PMID- 2590300 TI - Immunodeficiency associated with Dandy-Walker-like malformation, congenital heart defect, and craniofacial abnormalities. PMID- 2590301 TI - Prehospital pharmacological interventions. PMID- 2590302 TI - A simple method for determination of plasma thiocyanate. PMID- 2590303 TI - A clinical model for predicting survival... PMID- 2590304 TI - Combined spinal epidural for emergency caesarean section. PMID- 2590305 TI - Survival of and plasmid stability in Pseudomonas and Klebsiella spp. introduced into agricultural drainage water. AB - Cell survival and plasmid stability in Pseudomonas fluorescens R2f and Pseudomonas putida CYM 318 containing respectively, plasmid RP4 and pRK2501, and Klebsiella aerogenes NCTC 418 harboring plasmid pBR322 were studied in sterile and nonsterile agricultural drainage water under both aerobic and anaerobic conditions and in the absence and presence of added nutrients. Both Pseudomonas strains survived well in sterile drainage water incubated aerobically, with or without added nutrients. However, Klebsiella aerogenes NCTC 418 (pBR322) only survived in the presence of added nutrients. Pseudomonas fluorescens R2f (RP4) and K. aerogenes NCTC 418 (pBR322) did not survive under anerobic conditions without added nutrients, but showed good survival in the presence of nutrients. Survival of all three strains was negatively affected in nonsterile agricultural drainage water when compared with survival in sterile water. Maintenance of the three plasmids was host, plasmid, and environment dependent. Plasmid pBR322 was not stably maintained in K. aerogenes NCTC 418 under all conditions used in the study, and pRK2501 was readily lost from P. putida CYM 318. Maintenance of RP4 by P. fluorescens R2f was markedly influenced by added nutrients, which caused a loss of the plasmid from cells. The results of the present study demonstrate the influence of nutrients, O2, and native microorganisms on the survival of introduced bacterial strains and plasmid stability in agricultural drainage water. PMID- 2590306 TI - Increased arousal from steroids? PMID- 2590307 TI - Bilateral sensorineural deafness following pyogenic meningitis. PMID- 2590308 TI - Differential diagnosis of metastatic undifferentiated carcinoma. PMID- 2590309 TI - Utilization strategies for intensive care units. PMID- 2590310 TI - Dystonic posturing in temporal lobe seizures. PMID- 2590311 TI - Impacted Sengstaken Blakemore tube. PMID- 2590312 TI - Sparteine oxidation polymorphism: phenotyping by measurement of sparteine and its dehydrometabolites in plasma. AB - Phenotyping of the ability to oxidize sparteine was markedly facilitated by analyzing sparteine and dehydrosparteines in a single plasma sample by gas chromatography. The definitive identification of extensive and poor metabolizers was possible only 90 min after ingestion of 100 mg sparteine sulphate. In 121 healthy volunteers determination of the plasma level ratio was compared to the established determination of the metabolic ratio in urine. In each subject the alloted phenotype was the same by both methods. Plasma and urine analysis showed 9.9% of poor metabolizers. PMID- 2590313 TI - Fenoterol and death from severe asthma. PMID- 2590314 TI - Emergency room patients, chest pain, and thrombolysis. PMID- 2590315 TI - Genetic epidemiology of Greenland. AB - The Inuit (Eskimo) gene pool is in many respects similar to that of East Asian populations. Some polymorphisms imply frequent occurrence of disorders comparatively rare in Western Europe (e.g. lactose and sucrose malabsorptions). Low frequencies of alleles for slow isoniazid acetylation and sparteine/debrisoquine oxidation indicate slow elimination of a multitude of drugs. Autoimmune disorders (e.g. rheumatoid arthritis, insulin dependent diabetes mellitus, Graves' disease and psoriasis) are rare, possibly explained by the associations of these disorders with HLA-alleles rare in Inuit (e.g. HLA-B8). Correspondingly high incidence of reactive arthritis may be explained by a frequent HLA-B27 allele. Prevalence of disorders due to instability of mesenchymal tissues (e.g. spondylolisthesis, osteoarthrosis, hernia, heart block) are still in want of a biochemical explanation. Attention is drawn to the urgency of genetic studies in the Arctic because of the accelerating hybridization of Inuit in all circumpolar areas. PMID- 2590316 TI - Long-term outcome for children with congenital heart defects. A study from 1 year birth cohort born in 1966 in northern Finland. AB - The incidence of congenital heart defects (CHD) in a birth cohort of 12,058 live births born in Northern Finland in 1966 was 4.15/1000 with a mortality due to CHD 1.41/1000 up to 14 years of age. The long-term social and educational outcome for CHD children was significantly poorer than for normal children of the same age when evaluated on the basis of school and army service records, and the incidence of cerebral palsy, epilepsy and mental retardation was significantly higher. 15.4% of the Down's syndrome cases in the cohort also had CHD. The CHD boys were significantly lighter in weight than the controls even as adolescents (14 years of age). The only difference between the operated and non-operated group was the higher weight of the boys at the age of 18 years in the former. PMID- 2590317 TI - The quantitative and qualitative use of the Adaptability Questionnaire (ADQ). AB - The construction and use of the brief Adaptability Rating Questionnaire (ADQ) in a unique Antarctic field study is described, and comparisons are made between the ratings of a trained observer, a peer group and the subjects themselves. The indications are that the ADQ goes some way towards filling a need for rating scale to measure the adaptability of small groups to hostile and unusual environments. PMID- 2590318 TI - A serious outbreak of canine distemper among sled-dogs in northern Greenland. AB - A canine distemper outbreak in a highly susceptible sled dog population of Northern Greenland was recognized in the beginning of January 1988. A high morbidity and mortality in all age groups was a characteristic of the epizootic. The actual canine distemper virus infection was identified by isolation of the virus and demonstration of viral antigens by immunofluorescence and also by demonstration of conventional inclusion bodies. Virus specific IgM antibodies were demonstrated in affected dogs. In places where vaccination was carried out too late to be effective, the losses were up to 80 per cent. In a settlement, which was under rabies quarantine four weeks before the distemper outbreak started in other settlements, no cases occurred before or after vaccination. The spread of canine distemper seems connected with a Canadian outbreak and communicated by foxes. Once established the further spread apparently was by travelling dog teams. Suitable future prophylactic measures are discussed. PMID- 2590319 TI - Circadian variation of fibrinolytic activity among Eskimos in Greenland. AB - Recent studies on circadian variation of blood fibrinolytic activity have suggested a relation between a depressed morning fibrinolytic activity and the frequent onset of myocardial infarction at that time in Caucasians. We have obtained blood samples from 10 Eskimos with an interval of 4 h during 24 h and studied the extrinsic tissue-type plasminogen activator-related fibrinolysis. We observed a significant change in the activity of tissue-type plasminogen activator (t-PA; p less than 0.01) and in the activity of plasminogen activator inhibitor (PAI; p less than 0.001) during 24 h. The activity of t-PA increased more rapidly and the activity of PAI decreased more rapidly during the morning hours in Eskimos compared to reported patterns in Caucasians. A significant negative correlation between PAI and t-PA (r = -0.79, p less than 0.0001) suggested that PAI contributes to the regulation of t-PA activity in the blood. Whether the observations are of importance for the low prevalence of myocardial infarction in Eskimos remains to be further studied. However, our observations demonstrate that it is of utmost importance to standardize the collection of blood samples in order to obtain reliable information on the fibrinolytic system in Eskimos. PMID- 2590320 TI - Hudson-Stahli's iron-line of cornea in Eskimos. AB - The Incidence of Hudson-Stahli's iron-line of the cornea (HS) has been studied in 1988 in a series of 265 Eskimos in the Angmagssalik district, East Greenland, and compared with that among 287 Caucasians in Copenhagen, Denmark. The author employed the same method of investigation for both series. HS is absent in young Eskimos less than 19 years), but present in 8 to 20 per cent in the remaining age groups. Eskimos and Caucasians are alike with regard to incidence, binocularity, grade, colour, and site. This goes to show that HS is of endogenous origin, bearing no relation to the frequent occurrence of haemolacria, pterygium, and astigmatism among Eskimos. PMID- 2590321 TI - The use of the contact Nd:YAG laser in arthroscopic surgery: effects on articular cartilage and meniscal tissue. AB - The contact Nd:YAG laser's small size, tip variety, fiberoptic application, and suitability for use in a saline medium make it a particularly appealing tool for use in arthroscopic procedures. This study was performed to investigate the laser's effects on articular cartilage and meniscal tissue with respect to depth of damage (canine cadaver model) and healing response (rabbit model). Depth of damage in the canine cadaver model was greater in meniscal tissue than in articular cartilage at each wattage level. In the presence of a saline bath, depth damage in both tissues was diminished. Scalpel articular cartilage lesions showed no response over time. Electrocautery lesions uniformly showed significant wide margins of hyaline cartilage necrosis which increased over time. Laser articular cartilage lesions showed vigorous healing responses characterized by fibrocartilage healing by 6 weeks. Scalpel meniscectomies showed characteristic fibrocartilagenous remodeling by 6 weeks, while electrocautery meniscectomies showed wide margins of necrosis with no specimen showing remodeling capability. Laser meniscectomies showed an intermediate response with a small number of menisci remodeling in a normal fashion. This article represents the first comprehensive look at the effects of the Nd:YAG laser on articular cartilage and meniscal tissue in terms of depth of damage and healing response over time, and indicates this laser's biological advantage over scalpel and electrocautery in arthroscopic procedures. PMID- 2590322 TI - The incidence of Hill-Sachs lesions in initial anterior shoulder dislocations. AB - We undertook a prospective study using arthroscopy to determine the intraarticular derangement caused by initial anterior shoulder dislocations. Of our 32 patients, 15 (47%) had a grade I, grade II, or grade III Hill-Sachs lesion. The patients were 29 men and 3 women whose ages ranged from 15 to 28 years (mean 22 years). All of the patients studied were United States military personnel or members of their families. None of the patients had had prior injuries of the affected shoulder, and all underwent arthroscopy within 72 h of injury. Few reports describe a Hill-Sachs lesion in a patient following a single anterior dislocation. Early reports of this lesion were based on indirect (radiographic) evidence. Our arthroscopic findings indicate that the incidence of this lesion after one anterior dislocation is higher than previously thought. PMID- 2590323 TI - Articular cartilage lesions of the knee. AB - The pathogenesis and clinical significance of articular cartilage lesions of the knee persist as topics of considerable interest among orthopedic surgeons. This study was designed to assess the association of articular cartilage degeneration with concomitant intraarticular abnormalities and to correlate the prevalence and severity of articular cartilage damage with preoperative historical and physical exam findings in patients presenting with knee pain. Twenty-six history and physical exam data points were prospectively collected from 192 patients (200 knees), consecutively undergoing arthroscopic knee surgery. During surgery, all articular cartilage lesions were recorded with respect to size, location, and character and were graded according to Oglivie-Harris et al. All concomitant knee joint abnormalities were simultaneously recorded. Of 200 knees examined arthroscopically, 12 knees revealed no demonstrable etiology for the presenting symptoms, 65 knees revealed assorted intraarticular pathology but no articular cartilage degeneration, and the remaining 123 knees revealed a total of 211 articular cartilage lesions (103 femoral, 72 patellar, 36 tibial); 7 femoral, 6 patellar and 0 tibial lesions were completely isolated (no concomitant knee joint pathology). The concomitance of femoral defects with tibial lesions was highly significant (p = 0.01). Femoral and tibial articular cartilage lesions were strikingly correlated with the presence of an unstable torn meniscus (p less than 0.001). Medial compartment articular cartilage lesions were significantly more common (p = 0.001), more closely associated with meniscal derangement, and appreciably more severe than lateral compartment lesions. In 75% of anterior cruciate ligament-deficient knees with concomitant articular cartilage degeneration, the duration from injury to surgery was greater than 9 months, and in each of these cases, a history of reinjury to the knee was elicited. From these data one can conclude that: (a) in some patients with painful knees, isolated articular cartilage lesions may be the only abnormality noted at arthroscopy; (b) unstable meniscal tears are significantly associated with destruction of articular cartilage; (c) the medial compartment is particularly susceptible to articular cartilage degeneration; and (d) in our series, anterior cruciate ligament tears were increasingly associated with articular cartilage destruction as the elapsed time from injury to arthroscopy increased. PMID- 2590324 TI - Skeletal muscle hemangioma: a cause of unexplained pain about the knee. AB - Two cases of perplexing pain about the knee secondary to hemangioma of the vastus medialis are presented. The diagnostic criteria, pathological histology, and treatment are reviewed. Magnetic resonance imaging has distinct advantages over both computed tomography scans and angiography as a diagnostic tool. PMID- 2590325 TI - Cysts of the lateral meniscus: arthroscopy versus arthroscopy plus open cystectomy. AB - A retrospective analysis was performed on 32 knees in 31 patients with the diagnosis of cyst of the lateral meniscus. Average follow-up was 41 months, with a range of 16-72 months. Surgical and histological examination demonstrated pathology varying from large meniscal tears with minimal cyst formation to large cysts with no demonstrable meniscal tear. Two theories of etiology emerged: (a) The tear begins in the meniscus and spreads through the periphery. (b) The lesion begins as a compression injury to the vascular periphery and spreads centrally, producing a meniscus tear, or peripherally, producing a cyst, or both. In our series, 20 patients managed by arthroscopic partial meniscectomy and open cystectomy had 80% excellent-good results versus 50% excellent-good results in 12 patients treated with arthroscopy and partial meniscectomy without extraarticular cystectomy. We recommend the following treatment: arthroscopy with a diligent search for a lateral meniscal tear, especially peripherally. If none is found, proceed to extraarticular cystectomy. If a tear is found, remove all unstable meniscal fragments, leaving a rim, if possible, especially adjacent to the popliteus recess, and then proceed to open cystectomy. PMID- 2590326 TI - An analysis of complications in lateral retinacular release procedures. AB - Complications were reviewed for 446 lateral retinacular release procedures performed by 21 arthroscopic surgeons in various centers. There were 32 complications among the 446 procedures. The overall complication rate for lateral retinacular release was 7.2%. Information obtained from each individual surgeon in the study allowed scrutiny of various surgical techniques as they related to complications in lateral retinacular release procedures. Higher complication rates were noted with tourniquet use (p = 0.037), in arthroscopically controlled subcutaneous technique (p = 0.057), and most significantly, in the use of a postoperative suction drain for 24 h or longer (p less than 0.001). Electrocautery use did not affect the complication rate (p = 0.50). Outpatient procedures had no higher complication rate than inpatient procedures (p = 0.95). PMID- 2590327 TI - Accuracy of nonorthogonal magnetic resonance imaging in acute disruption of the anterior cruciate ligament. AB - A controlled, prospective study of 30 patients with suspected acute internal derangement of the knee was undertaken to evaluate the sensitivity, specificity, predictive value, and accuracy of nonorthogonal (oblique) sagittal magnetic resonance imaging (MRI) in the assessment of anterior cruciate ligament (ACL) injuries. Thirty patients with acute hemarthroses underwent MRI within 12 days of injury, followed by arthroscopy within 24 h of the MRI. A control population of 30 chondromalacia patients underwent similar evaluation. In the acute hemarthrosis patient population, the incidence at arthroscopy of acute complete ACL tears was 60% (18/30); of partial ACL tears, 13.3% (4/30); and of chronic tears, 10% (3/30). A normal ACL was found in 16.6% (5/30) of patients. In the MRI evaluation of patients with suspected ACL injury the following results were obtained for both acute and chronic complete disruption on orthogonal (sagittal) and nonorthogonal (oblique sagittal) imaging, respectively: sensitivity, 61 (16/26) versus 100%; specificity, 70 (21/34) versus 100%; positive predictive value, 61 (16/26) versus 100%; negative predictive value 70 (24/34) versus 100%; and accuracy, 66 (40/60) versus 100%. In the evaluation of partial ACL injury, four partial tears were correctly diagnosed on nonorthogonal MRI, with one false positive diagnosis. Orthogonal imaging failed to correctly identify any of the partial ACL injuries. Two patients in the control population demonstrated evidence of chronic ACL tears. We believe that we have demonstrated the superiority of T2-weighted nonorthogonal sagittal over conventional orthogonal sagittal ACL MRI in the evaluation of ACL injury. PMID- 2590328 TI - Arthroscopy of the painful dysfunctional total knee replacement. AB - Arthroscopy of the painful failed total knee arthroplasty has rarely been reported. The indications and results in terms of diagnosis and treatment of pathologic conditions in 13 knees after total knee arthroplasty are reviewed. Arthroscopy established the diagnosis for pain in 12 of 13 knees. Several problems were commonly encountered, including arthrofibrosis and fracture of the polyethylene button. Arthroscopic surgery for arthrofibrosis was successful in improving range of motion and knee-rating score. PMID- 2590329 TI - Three irrigation systems for motorized arthroscopic surgery: a comparative experimental and clinical study. AB - The purpose of this study was to compare experimentally and clinically three types of irrigation systems for arthroscopic suction surgery. A joint model was used in the experimental part of the study. It was found that a combination of inflow from a volume pump with extra gravity inflow through a separate cannula gave results comparable to those with more sophisticated automatic pumps. Clinically, none of the systems provided protection from high-pressure peaks during rapid movements of the knee joint. It was also found that the pressure differed in the superior and posteromedial compartments of the knee during rapid movement. PMID- 2590330 TI - Arthroscopy and stability testing for anterior shoulder instability. AB - The extreme manifestation of anterior shoulder instability is anterior dislocation. Minor anterior instability often gives rise to vague symptoms from which a diagnosis is difficult. The use of arthroscopy may increase diagnostic accuracy in cases of anterior shoulder instability. Examinations were performed on 145 patients with shoulder complaints using stability testing under anesthesia and arthroscopy; of these, 62 patients were found to have anterior shoulder instability. The clinical signs were compared with the findings on stability testing and arthroscopy, and the morphological changes noted on arthroscopy were recorded. The combination of arthroscopy and stability testing proved valuable in the diagnosis of minor anterior instability and for the morphological changes and associated injuries in established anterior dislocations. PMID- 2590331 TI - Arthroscopic subacromial decompression versus open acromioplasty. AB - A random prospective comparison was conducted of 20 patients who underwent arthroscopic subacromial decompression or open acromioplasty as treatment for impingement syndrome. The Neer anterior acromioplasty served as comparison in the evaluation to arthroscopic technique. The comparison shows more rapid rehabilitation and better range of motion in the arthroscopic group. Time of surgery is also shorter for arthroscopy than for the open technique. Arthroscopic subacromial decompression appears to be superior to open acromioplasty as a treatment for impingement syndrome. PMID- 2590332 TI - Early arthroscopic evaluation of acute repair of the anterior cruciate ligament. AB - Follow-up arthroscopy was performed in 71 patients who had undergone primary repair of an acute rupture of the anterior cruciate ligament (ACL) after 6-19 months. An augmented repair was done on 61 patients and 10 patients had a nonaugmented repair. Based on the arthroscopic findings, the ACL repair was classified into three categories. Four years after the injury a clinical reexamination, including a laxity test using instrumentation and a standard knee function test, was done on 66 patients. Arthroscopy revealed that 64 of the 71 patients (90%) had a defined ACL repair, although the repair was elongated in 37 patients. Seven patients with a nonfunctioning ACL repair had inferior knee function after 4 years. Arthroscopy also showed superficial cartilage lesions in 24 patients and meniscal pathology in 6 patients. Two patients with more advanced chondral lesions had inferior knee function. Treatment of meniscal injuries did not affect the long-term results. PMID- 2590333 TI - Pigmented villonodular synovitis of patellar plica. AB - This article reports a rare case of pigmented villonodular synovitis (PVS) arising from the plica synovialis mediopatellaris that impeded the knee joint when it was extended. This lesion was diagnosed and treated by arthroscopy. PMID- 2590334 TI - Prepatellar bursitis: a complication of arthroscopic surgery of the knee due to a lost meniscal fragment. AB - The case report of a patient with prepatellar bursitis resulting from a retained meniscal fragment following arthroscopic surgery is presented. The potential for the development of this condition is explained based on the anatomic position of the prepatellar bursa and its relationship to the arthroscopic portals. PMID- 2590335 TI - Subcutaneous joint-mouse escape during knee-joint arthroscopy. AB - During arthroscopy of the knee, large volumes of fluid are required. Cadaver studies have indicated that flexion of the knee may cause rupture of the joint capsule during arthroscopy. To illustrate this, a rare case is presented with rupture of the posterior part of the capsule during arthroscopy with extrusion of a joint mouse. This possibility should be considered when the joint mouse cannot be found inside the joint during arthroscopy. PMID- 2590336 TI - Oregon's Patrick case and Supreme Court decision. AB - Does the Patrick decision affect properly done peer review used to consider quality patient care? The answer is most definitely no! If guidelines are followed that abide by the HCQIA and hospital peers review bylaws, then one can be fairly certain that physician reviewers are, indeed, immune to most liability challenges (one should remember, however, that compliance with HCQIA only provides immunity from federal and state law private claims, and not actions by the U.S. Department of Justice as a State Attorney General, i.e. criminal antitrust claims). We must be aware of and revise where necessary to conform to HCQIA our own hospital medical staff bylaws and policies as well as state procedural and reporting policies. We have learned that anticompetitive acts in the business of medicine are dealt with under the law no differently than anticompetitive acts in any other business. We must be aware of antitrust laws and remember as an extension of Patrick that medical groups dealing with alternative health delivery systems and joint ventures must consider any anticompetitive aspects of proposed contracts. Failure to do so could put us in jail. PMID- 2590337 TI - The use of intraarticular bupivacaine. PMID- 2590338 TI - [Infections in patients with cancer, criteria for quality of nursing care]. AB - In this paper the factors that lead to nosocomial infections of hospitalized patients with cancer and prophylaxis measures are discussed. Infection is the primary cause of death for the individual with cancer. The typical signs and symptoms often are absent in these patients. Although Gram negative organisms account for the majority of infections today, an increase of nonbacterial infections is noted. "Good" nursing care of these patients is the major factor in preventing and minimizing the incidence of nosocomial infections and it is an indicator of quality care. PMID- 2590339 TI - [The development of primary health care in the world, Europe and Greece]. AB - This brief review describes the development of Primary Health Care (PHC) in all countries of the world and the main factors which urged the World Community to adapt the PHC as the "key" for the attainment of the goal "Health for All by the year 2000". In addition, emphasis is given to the role and the contribution of Nursing to the achievement of the above goal. PMID- 2590340 TI - [Organization of a central supply system for nursing units]. AB - The provision of supplies for a hospital, wards and nursing units, must be undertaken carefully. The financial side as well as the suitability and the quality of the equipment must be taken into consideration for an effective patient nursing care. A central supply system for a hospital is considered as a more economical and effective one. By this way nursing staff relieved from no nursing duties, thus they can devote more time to direct patient care in the unit. PMID- 2590341 TI - Purification and properties of arogenate dehydrogenase from Actinoplanes missouriensis. AB - Actinoplanes missouriensis utilizes arogenate as an intermediate in L-tyrosine biosynthesis, while no evidence of prephenate dehydrogenase was observed. Arogenate dehydrogenase has been partially purified by a five-step procedure. The enzyme requires NAD as cofactor. The Km values for NAD and arogenate are 0.2 mM and 0.15 mM, respectively. The molecular weight of arogenate dehydrogenase is about 68,000, and SDS gel electrophoresis indicates a composition of two identical subunits. The enzyme is not feedback inhibited by L-tyrosine and unaffected by L-phenylalanine, prephenate, phenylpyruvate, p hydroxyphenylpyruvate or L-tryptophan. Arogenate dehydrogenase is quite sensitive to p-hydroxymercuribenzoate with 50% inhibition at 12.5 microM of the SH-specific reagent. The presence of malate in usually applied arogenate preparations is demonstrated and the consequence of an impure substrate on arogenate dehydrogenase studies is discussed. PMID- 2590342 TI - Stimulation of myoblast membrane protein synthesis by 25-hydroxy-vitamin D3. AB - The effects of 25-hydroxy-vitamin D3 (25 OHD3) on myoblast protein synthesis were studied in connection with its role on muscle cell phosphate metabolism. The sterol markedly increased leucine incorporation into total cell proteins in cultured chick embryo myoblasts. This enhancement was greater than that produced by 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) and occurred prior to a significant stimulation of cell phosphate accumulation. Maximum effects of 25 OHD3 (8 h) on myoblast phosphate uptake were suppressed by cycloheximide indicating that they are mediated by de novo protein synthesis. At a similar treatment period, labelling of myoblasts with [3H]leucine (control) and [14C]leucine (+25 OHD3) followed by co-electrophoresis of total protein extracts on SDS-PAGE and isoelectrofocusing gels revealed that the sterol selectively affects the synthesis of proteins of 20 kDa and 50 kDa. These macromolecules were recovered in the microsomal fraction after differential centrifugation of homogenates. Further fractionation of myoblast microsomes on sucrose density gradients showed co-localization of the 50 kDa and 20 kDa proteins with microsomal subfractions which preferentially bind [3H-alpha]bungarotoxin, suggesting that the proteins induced by 25 OHD3 are associated to plasma membranes and may play a role in the effects of the sterol on cell phosphate uptake. PMID- 2590343 TI - Preparation and isolation of antibodies to human MHC class II alpha chains by aid of synthetic peptides. AB - Antibodies against HLA Class II alpha chains were prepared by using as immunogens synthetic peptides selected from the HLA-DQ1 alpha chains sequence. Antibodies raised against peptide E2, a 15-residue fragment of the polymorphic first domain, reacted preferentially with cells with the DQ1 phenotype; however, despite the low sequence homology of this fragment with corresponding segments in DQw2 and DQw3 alpha chains, a partial crossreactivity with cells not expressing the DQw1 specificity was detected. Antibodies to peptide H, selected from the monomorphic frame, might be specific for DQ alloantigens, and presumably do not react with DR antigens. The two peptides, in addition, bind anti-Class II antibodies from the serum of a rabbit immunized with human cells, and appear to represent immunogenic linear determinants in the native glycoprotein molecule. PMID- 2590344 TI - Role of thiols in radioprotection: radiation chemical aspects. AB - Using the technique of pulse radiolysis, it has been demonstrated that thiyl radicals (RS.) derived from glutathione (GSH), cysteine (CYSH), penicillamine (PnSH) and 2-mercaptoethanol (ME) interact with oxygen at a high rate. The resulting transient absorption, with a maximum around 540-560 nm, is characteristic of the sulphur peroxyl radical (RSOO.). The yield and the kinetic of formation of RSOO. further support our previous suggestion that thiyl/O2 reaction is an equilibrium. The redox properties of RSOO. are discussed on the basis of the interaction with reductants. Studies on the radio-induced enzyme inactivation in the presence of thiols seem to suggest a damaging role for RSOO. radicals. PMID- 2590345 TI - Specificity of anti-MHC class II antibody binding to synthetic peptides. AB - This study indicates that antibodies raised against a DR4,w6; DQw1,3 positive cell line may bind to synthetic peptides selected from the polymorphic amino acid sequences 51-59 and 63-79 on the DQw2 beta chain. This cross-reaction may be explained by the relatively high sequence homology of these sequences in the beta chains of class II histocompatibility antigens, and suggests that antibody binding to small peptides may be scarsely selective. Based on the observations of the reactivity of the antibodies with several cell lines, and comparison of the amino acid sequences of beta chains of DR and DQ molecules, an attempt to identify the cross-reacting epitope is presented. PMID- 2590346 TI - Teaching medical ethics. PMID- 2590347 TI - Teaching medical ethics: some persistent questions and some responses. PMID- 2590348 TI - Teaching medical ethics: a hard-won beachhead. PMID- 2590349 TI - The Baylor experience in teaching medical ethics. AB - This paper describes the activities of the Center for Ethics, Medicine, and Public Issues, a joint project of Baylor College of Medicine, the Institute of Religion of the Texas Medical Center, and Rice University. The center focuses on the clinical teaching of medical ethics, collaborative teaching and research involving ethicists and clinicians, and the training of future practitioners in the field. Problems as well as achievements in each of these areas are discussed. PMID- 2590350 TI - Medical ethics teaching programs at the University of California, San Francisco, and the University of Washington. AB - The author describes the comparative dearth of scholarship and literature on medical ethics in 1972 when he began designing an elective lecture-discussion course at the School of Medicine, University of California, San Francisco (UCSF). He traces the development of ethics teaching at that school and of his conviction that medical cases must be the focus of ethics education, not merely as illustrations but as the matrix of the ethical problems encountered and their resolution. Eventually, a required fourth-year course was developed that focused upon four essential aspects of medical cases: medical indications, patient preferences, quality of life, and external socioeconomic factors. This course and its evaluation--including inherent quandaries of evaluating ethics teaching--are described; he attributes the success of the course to the appropriateness of the four-part format for analysis and the support and participation of leading members of the medical faculty. Throughout this description of the UCSF program are short descriptions of the additions to the bioethics literature that were made during the mid- and late 1970s. The author then describes the present ethics teaching program at the University of Washington School of Medicine, where he has taught since 1987, and the intriguing and perhaps innovative possibilities for expanding and redefining that program. PMID- 2590351 TI - Development of a teaching program in clinical medical ethics at the University of Chicago. AB - The University of Chicago Pritzker School of Medicine has developed and evaluated an extensive teaching program in clinical ethics coordinated primarily through the Center for Clinical Medical Ethics. The program provides medical students with a foundation in medical ethics during the four years of medical school and augments the clinical ethics knowledge and teaching skills of the housestaff and clinical faculty at the University of Chicago. Together, medical student teaching and clinical faculty development have made clinical ethics an integral part of medical education at the University of Chicago. Through these efforts, the teaching program aims to incorporate clinical ethics considerations into medical decisions and in this way contribute to improving patient care. (A detailed overview of all clinical ethics instruction at the school is provided.) PMID- 2590352 TI - Development of the medical humanities program at East Carolina University. AB - The medical humanities program at East Carolina University School of Medicine has 50 contact hours with medical students in the required curriculum, fourth-year electives that are well-subscribed (47% of the members of the class of 1989 took one or more), and programs for residents, fellows, and faculty. The author discusses several crucial decisions made in the first year of the program (1978 79) that affected the nature and development of the program: first, to begin the medical humanities courses in the preclinical required curriculum and use these courses as a base to build on in the clinical years; second, to develop a program through all years of training while preserving time for faculty research; third, to arrange for program faculty to team-teach with clinical faculty; fourth, to show the importance of the humanities programs and courses by the way in which they were constructed and situated in the curriculum; and fifth, to seek primarily to teach a method of inquiry. PMID- 2590353 TI - The clinical medical humanities program at Loyola University of Chicago. AB - The authors emphasize that an effective medical humanities program must be based on clinically oriented training. They then describe in detail such a program at Loyola University of Chicago Medical Center; the program consists of a four-year required curriculum that is clinically reinforced by having the students accompany attending physicians on rounds and is taught by faculty representing a wide range of disciplines in medicine and other fields. The paper offers several guidelines to the person or persons who would organize and direct a clinical medical humanities program, describes obstacles that the Loyola program faced when it was getting started, presents the purpose, focus, and curricular topics of the program, and discusses its future. The authors conclude that the use of the clinically oriented approach will continue to prevail in medical humanities teaching, both at Loyola and in medical humanities programs overall. This approach challenges good teachers to make their best efforts at reconciling their own disciplines with that of medicine; in this process, a new medical humanities discipline emerges that is not so much an application of the humanities to medicine as it is an evocation of humanities themes from the clinical encounter itself. PMID- 2590354 TI - Ethics education at Northwestern University Medical School. AB - The Northwestern University Medical School's Ethics and Human Values Program spans the medical curriculum from first year to fourth and extends into several residency programs. Taught by scholars in the medical humanities and clinicians from almost every specialty, the courses and seminars draw upon philosophy, literature, and law in addressing both immediately pressing social issues and the enduring "everyday ethics" of the physician-patient relationship. PMID- 2590355 TI - Teaching medical ethics in its contexts: Penn State College of Medicine. AB - Ethics teaching at The Pennsylvania State University College of Medicine began when the medical school accepted its first students in 1967. The ethics program co-evolved with the school and the Department of Humanities without guidelines or models, since neither medical ethics nor medical humanities had yet been invented as fields of study. The focus of the article is on two key differences between the Penn State ethics program and most other such programs: the teaching of medical ethics within the context of other issues of value and meaning in medicine, and the fact that the humanities faculty is involved in the activities and structures of the medical center of which the medical school is a part. The authors close with a description of successful factors in their program that they maintain could apply to other programs. PMID- 2590356 TI - Evolution of clinical ethics teaching at the University of Pittsburgh. AB - The authors explain that several years of effort, by many faculty from a variety of disciplines, were required to expand medical ethics teaching at the University of Pittsburgh School of Medicine beyond the preclinical years. Since 1986, faculty associated with the school's Center for Medical Ethics have begun a comprehensive ethics teaching program for all four years and the residency period; they also are attempting to develop an ethics consultation service. The authors describe the program, its promise and plans, and the significant difficulties involved in establishing and maintaining it, not only problems of long-term funding but of the uninformed and negative attitudes of some students and faculty toward ethics teaching, especially in the clinical setting. Also discussed are the pros and cons of using cases in ethics teaching and the program's approaches to evaluation and to training clinical faculty in clinical ethics issues. PMID- 2590358 TI - The effect of teaching medical ethics on medical students' moral reasoning. AB - A study assessed the effect of incorporating medical ethics into the medical curriculum and the relative effects of two methods of implementing that curriculum, namely, lecture and case-study discussions. Results indicate a statistically significant increase (p less than or equal to .0001) in the level of moral reasoning of students exposed to the medical ethics course, regardless of format. Moreover, the unadjusted posttest scores indicated that the case-study method was significantly (p less than or equal to .03) more effective than the lecture method in increasing students' level of moral reasoning. When adjustment were made for the pretest scores, however, this difference was not statistically significant (p less than or equal to .18). Regression analysis by linear panel techniques revealed that age, gender, undergraduate grade-point average, and scores on the Medical College Admission Test were not related to the changes in moral-reasoning scores. All of the variance that could be explained was due to the students' being in one of the two experimental groups. In comparison with the control group, the change associated with each experimental format was statistically significant (lecture, p less than or equal to .004; case study, p less than or equal to .0001). Various explanations for these findings and their implications are given. PMID- 2590357 TI - The development of a medical ethics curriculum in a General Internal Medicine Residency Program. AB - Since 1984, a three-year curriculum in medical ethics has operated at Rhode Island Hospital as part of the General Internal Medicine Residency Program at the Rhode Island Hospital and Brown University. The residency program was founded in 1980 to develop a model training program for internal medicine residents with a primary care focus. The three objective of the curriculum are (1) to enable residents to recognize the ethical implications of both inpatient and outpatient clinical cases, (2) to teach residents to recognize ethics issues and alternatives in order to arrive at a well-rounded clinical strategy, and (3) to help them learn to communicate sensitively with patients and others about these ethics issues and proposed management plans. The six major topics covered by the curriculum (for example, informed consent) are co-taught in a seminar format by one or more of the three members of the multidisciplinary ethics faculty (a philosopher, an internist, and a communications specialist) and experienced physicians. The authors describe the program, the roles of the various faculty members, the program's focus on case discussions, the receptivity of the residents and faculty to the program, the use and training of a multidisciplinary faculty, efforts aimed at evaluation, and future directions of the program. PMID- 2590359 TI - Internal medicine residents' preferences regarding medical ethics education. AB - Three hundred and twenty-three residents in six internal medicine programs in three states were surveyed concerning what they wanted to learn about medical ethics and how they would prefer to learn it; they were also asked to indicate what medical ethics education they had already received. Specifically, the residents were given a list of 35 medical ethics topics and asked to indicate whether they would like more attention to a topic, or whether it had received enough or too much attention. (They could also indicate that they though the topic was inappropriate for attention during residency.) The residents were also given a list of 17 teaching methods for medical ethics and asked to indicate whether each method was very useful, somewhat useful, or not useful. Sixty-one percent of the residents responded. Approximately three-fourths of these had had some formal teaching about medical ethics in both medical school and residency, and nearly all indicated that they wanted more ethics training on specific topics. Certain topics were chosen as particularly suitable or unsuitable for such training; many of those judged as deserving more attention concerned legal issues and end-of-life issues. Most of the responding residents regarded standard clinical teaching formats as very useful for learning about medical ethics but regarded several other methods are not useful. The authors discuss the implications of these and related findings. PMID- 2590360 TI - Evaluating clinical teachers for promotion. PMID- 2590361 TI - The Animal Facility Protection Act: common sense for the common good. PMID- 2590363 TI - Student-family program. PMID- 2590362 TI - Animals in research. PMID- 2590364 TI - 3,5-Diphenyl-1H-pyrazole derivatives. III--Esters from 1-(2-hydroxyethyl)-3,5 diphenyl-1H-pyrazole and its 4-bromo derivative with hypotensive, depressant, antiarrhythmic and analgesic activities. AB - The synthesis of dialkylaminoalkyl ethers (III a-g) by reaction of 1-(2 hydroxyethyl)-3,5-diphenyl-1H-pyrazole (I) sodium salt with a series of omega chloroalkyldialkylamines is described. Cyanoethylation of alcohol (I) and its 4 bromo derivative (II) gave 2-cyanoethyl ethers (III h, i), one of which (III h) was hydrolyzed to the corresponding carboxylic acid. Cyanoethylation of 3,5 diphenylpyrazole (IV) and its 4-bromo derivative (V) yielded nitriles (VI) and (VII), respectively, which were hydrolyzed to the corresponding carboxylic acids (VIII) and (IX). Some of the above compounds showed considerable hypotensive, depressant, antiarrhythmic and analgesic activities in mice and rats, as well as a remarkable platelet antiaggregating activity in vitro. Moreover, the above compounds usually exhibited a moderate antiinflammatory activity in rats and infiltration anesthesia in mice. PMID- 2590365 TI - Molecular electrostatic potential-anthelmintic activity relationships of 5H mebendazole and some related heterocyclic carbamates. AB - 5H-Mebendazole and some related heterocyclic methyl carbamates were synthesized and their anthelmintic activity against Caenorhabditis elegans was determined. In order to study the influence of the heteroaromatic region with regard to the carbamate moiety on biological activity, the molecular electrostatic potentials (MEP) of all structures were calculated and a structure-activity relationship (SAR) was established. The electrostatic pattern of activity includes two minima of the carbamate moiety, a third heterocyclic minimum, and a pi-electronic region. PMID- 2590367 TI - Individual degradation rate constants for cefotaxime, deacetylation profile. AB - The individual degradation rate constants for cefotaxime in aqueous solution were calculated within a pH range of 1.6-10.0 at 37 degrees C from high performance liquid chromatography data. This allowed the general degradation profile of cefotaxime to be decomposed into a degradation profile attributed to the opening of the beta-lactam nucleus and a degradation profile attributed to the deacetylation. From the calculations of the individual rate constants, the activity of degraded cefotaxime solutions could be predicted. In the pH range of injectable solutions of cefotaxime 5-7, roughly equivalent amounts of inactive beta-lactam cleavage products and deacetylated compound which has a different spectrum of antibacterial activity are formed. PMID- 2590366 TI - Substituted phenylthiophenylamines with antiinflammatory activity. AB - Several acid and closely related non acid derivatives of 2-phenylthio- and 4 phenylthio-N-acyl phenylamines have been synthesized and tested in vivo, on the carrageenan RFE assay, and in vitro, on prostaglandin synthesis inhibition assay. Compound (XV c), bearing a propanoic acid substituent together with a p chlorobenzoyl group situated on nitrogen atom in the 2-position, showed a 79% edema reduction (300 mg/kg p.o.) 6 hours after carrageenan injection, but no activity in vitro. The benzyl alcohols (XIV m) and (XIV n), on the contrary, inhibited PG synthesis; their lack of activity in vivo could be interpreted as the result of their oxidation to the inactive benzoic acids (XIV g) and (XIV h). PMID- 2590368 TI - Synthesis of some 1,2,4-triazolo [3,4-b] [1,3,4]thiadiazoles as potential anthelmintics. AB - Two novel series of triazolothiadiazole derivatives were synthesized, namely: 6 substituted-3-(4-substituted phenoxymethyl)-1,2,4-triazolo[3,4- b] [1,3,4]thiadiazoles and 6-mercapto-3-(4-substituted phenoxy-methyl)-1,2,4 triazolo[3,4- b] [1,3,4]thiadiazoles. The anthelmintic activity of representative compounds was studied. PMID- 2590369 TI - Evaluation of monomethoxypolyethyleneglycol derivatized superoxide dismutase in blood and evidence for its binding to blood cells. AB - A method to evaluate in blood free superoxide dismutase (SOD) and SOD covalently bound to monomethoxypolyethylene glycol (MPEG-5000) is reported. The method takes advantage of gel filtration and cationic exchange chromatography to remove substances present in plasma which can interfere with the SOD enzymatic assay. Using this methodology, it was demonstrated that, contrary to free SOD, MPEG-SOD, when added to blood, was not completely recovered in plasma. Binding of MPEG-SOD to blood cell components takes place involving interactions of MPEG chains with cell membranes. PMID- 2590371 TI - Sustained release isoniazid tablets. I--Formulation and in vitro evaluation. AB - Isoniazid (INH) has been widely used in the preventive therapy of tuberculosis since the early 1950's. The aim in designing a sustained release tablet form was to attain in fast inactivators sustained blood concentrations similar to those produced by ordinary INH tablets in slow acetylators during chemotherapy. In the present paper, the release of INH incorporated into three different matrix materials, polymethylmethacrylates, polyvinyl chloride and carbomer were studied. The release rate of a unit dose of conventionally formulated INH tablets was used as a basis of comparison. The best sustained effect on the release rate of INH was obtained with 30% carbomer matrix tablets. PMID- 2590370 TI - Use of the crushing strength parameter for quality control of phenobarbital microcrystalline cellulose tablets. AB - Three variables of the tablet manufacturing process (duration of mixing with lubricant, maximum compression force and compression rate) were studied for their effects on various properties of direct compression phenobarbital microcrystalline cellulose tablets. Mixing time and maximum compression force were found to have a marked influence on friability and dissolution rate; crushing strength was found to be a useful parameter for quality control. PMID- 2590372 TI - Synthesis and CNS activity of some new substituted indeno [1,2-c] pyrazoles. AB - Some new 1-(6'-substituted-4'-methylquinol-2'-yl)-3-methyl-indeno[1,2- c]pyrazoles (Va-d) have been synthesized by the condensation of 2-acetylindane 1,3-dione (I) with 2-hydrazino-4-methyl-6-substituted quinolines (IIa-d), followed by cyclodehydration with polyphosphoric acid and Wolff-Kishner reduction. Compounds (IVa-d) showed noticeable CNS activity. PMID- 2590373 TI - High-performance liquid chromatographic determination of tilidine in pharmaceutical dosage forms. AB - A reversed-phase high performance liquid chromatographic method for the determination of tilidine in bulk drug and its liquid and solid dosage forms is described. The method uses reversed-phase column RP-8 with methanol -0.2% water solution of ammonium carbonate (75:25,v/v) as the mobile phase and UV detector. The time taken for separation is 6.17 min. The response is linear up to 3.6 mmol/l, with recovery levels ranging from 98.2 to 101.2%. The present method is rapid, simple and reproducible. PMID- 2590374 TI - Monosymptomatic delusions of parasitosis associated with ischemic cerebrovascular disease. AB - Monosymptomatic delusion of infestation (parasitosis) occur in idiopathic psychoses but have rarely been observed in patients with neurologic or systemic illnesses. A patient was observed in whom the delusion occurred in the presence of demonstrable cerebrovascular disease. The delusional symptoms were contralateral to the principal site of ischemic injury. Delusions of infestation may reflect an acquired neurologic or metabolic disorder, and medical and neurologic evaluation should be pursued in elderly patients presenting with this syndrome. PMID- 2590375 TI - Psychiatric commitment of the elderly. AB - Involuntary hospitalization of the elderly has been the focus of controversy. In many jurisdictions, commitment criteria are stringently and narrowly defined, require a showing of "dangerousness," and are difficult to apply toward securing proper treatment for the elderly. In other areas, broader criteria apply, but some authors argue that such criteria are inappropriately used with the elderly and leave them vulnerable to the abuse of unnecessary institutionalization. The authors examined 274 consecutive admissions aged 55 years and over, comparing voluntary and involuntary patients. Patients admitted involuntarily were significantly more likely to have organic mental disorders, be violent before admission, and be disoriented, withdrawn, and apathetic. Voluntary patients were significantly more likely to have major mood disorders. Patients who lived with others were more likely to be committed than those living alone. The authors discuss these findings with attention to the appropriateness of broader commitment standards and the more stringent dangerousness criteria as they apply to the geriatric population. PMID- 2590376 TI - Lexical processing in Parkinson's disease and multiple sclerosis. AB - Patients with Parkinson's disease (PD) or multiple sclerosis (MS) were categorized as normal in naming (NN) or impaired in naming (IN) based on their performance on the Boston Naming Test. All patients scored at least 23 on the Mini-Mental State Examination. Both PDIN and MSIN patient groups exhibited poor naming performance when target words were elicited with semantic, visual or rhyming cues. They also performed poorly on the vocabulary subtest of the Wechsler Adult Intelligence Scale-Revised and had difficulty repeating sentences. PDNN and MSNN patients showed more selective deficits. These findings add to a growing literature demonstrating that language in general, and naming in particular, can be compromised in subcortical diseases even when global mental status is only mildly affected. The clinical implications of these observations are, however, unclear. PMID- 2590377 TI - Access to semantic memory in Parkinson's disease and multiple sclerosis. AB - The capacity to access semantic memory and the efficiency of the memory search were studied in patients with Parkinson's disease (PD) or multiple sclerosis (MS) using a modified version of the "Supermarket Test." PD and MS patients who performed normally on the Boston Naming Test generated as many specific exemplars and category labels as did controls, and these patients also searched their semantic memories as efficiently as controls. In contrast, PD and MS patients with impaired confrontational naming generated fewer specific exemplars, but a normal number of generic category labels. These naming-impaired patients searched their semantic memories less efficiently than controls. For both MS and PD patients, the efficiency of semantic memory search was significantly correlated with measures that reflect access to semantic memory (eg, performance on letter or category fluency tasks), but was not significantly related to measures of problem-solving ability derived from the Wisconsin Card Sorting Test. Inefficient search of semantic memory in MS and PD appears to arise from an inability to retrieve knowledge from semantic memory quickly or from the loss of information from semantic memory stores, rather than from impairment in the ability to formulate and deploy appropriate strategies for task solution. PMID- 2590378 TI - Subspecialty boards in psychiatry. PMID- 2590379 TI - Immunogenicity signals 1,2,3 ... and 0. AB - The most critical property of the immune system is its ability to discriminate self from nonself. Failure to respond to nonself can lead to overwhelming infection, while failure in the ability not to respond to self, or self tolerance, leads to autoimmunity. A meeting held in Steamboat Springs focused on this issue under the title of 'Immunogenicity'. This brief summary focuses on one of the key issues considered at this conference - the signals involved in the induction of lymphocyte activation. In addition, an hypothesis of immune system function that appears to follow from these findings is described. PMID- 2590380 TI - Targeted cancer treatment. AB - The fourth international conference on monoclonal antibody immunoconjugates for cancer heard of great progress in the area of radioimmunoconjugates, and of continued research into the potential of immunotoxins, chemoimmunoconjugates and anti-immunoglobulin therapy as potential cancer therapies. PMID- 2590381 TI - Structure of rhesus monkey relaxin predicted by analysis of the single-copy rhesus monkey relaxin gene. AB - The gene encoding rhesus monkey relaxin has been investigated. A cDNA library was prepared using corpus luteal RNA from a pregnant rhesus monkey, cDNA clones encoding relaxin were isolated and the nucleotide sequence was determined. The amino acid sequence of rhesus monkey preprorelaxin, predicted from the cDNA, demonstrates that the sequence has not been strongly conserved when compared with that of man, although features characteristic of the relaxin molecule have been maintained. This structural information will allow production of rhesus monkey relaxin, leading to studies investigating the bioactivity of relaxin in a homologous primate system. Southern blot analysis indicated that there is only one relaxin gene in the rhesus monkey and baboon genomes. In this respect these primate genomes are different from the human genome which contains two relaxin genes. PMID- 2590383 TI - Metabolism of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3 and its sensitivity to ketoconazole in 1 alpha,25-dihydroxyvitamin D3-differentiated HL60 cells. AB - Regulation of the metabolism of [3H]25-hydroxyvitamin D3 ([ 3H]25-(OH)D3) in vitro to material with the characteristics of [3H]24,25-dihydroxyvitamin D3 ([3H]24,25-(OH)2D3) has been studied in the human promyelocytic cell line HL60. Synthesis of 24,25-(OH)2D3 was induced in a dose-dependent manner in cells pretreated with 0.1-100 nM 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) for 4 days. This treatment also inhibited cell proliferation and stimulated differentiation to a macrophage phenotype that was characterized by staining for non-specific esterase (NSE) activity. The ability to synthesize [3H]24,25-(OH)2D3 from [3H]25-(OH)D3 and the expression of NSE activity both responded to changes in concentration of 1 alpha,25-(OH)2D3 in the culture medium in a parallel manner. Synthesis of [3H]24,25-(OH)2D3 was linear when the incubation time was between 1 and 8 h and the cell number between 1 and 12 x 10(6) cells/incubation. The optimum substrate concentration for its synthesis was 125 nM, giving an apparent Michaelis constant of 360 nM. The identity of the [3H]24,25-(OH)2D3 synthesized by these cells was confirmed by co-chromatography with authentic 24,25-(OH)2D3 on normal-phase and reverse-phase high-performance liquid chromatography systems and by its reaction to sodium-m-periodate. Cells that had been exposed to 100 nM 1 alpha,25-(OH)2D3 for 4 days synthesized 2.17 +/- 0.07 (S.E.M.) pmol 24,25-(OH)2D3/10(6) cells per h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590382 TI - Insulin-like growth factor-I and its autocrine role in growth of MCF-7 human breast cancer cells in culture. AB - Human MCF-7 breast cancer cells have been studied to determine their suitability as an autocrine model for the synthesis, secretion and action of insulin-like growth factor-I (IGF-I). Secretion of immunoreactive (ir-) IGF-I into serum-free medium was very low (less than 500 pg/10(6) cells per day). Northern blot hybridization detected at least two IGF-I messenger RNA transcripts (approximately 4.6 and approximately 1.8 kb) which were similar in size to those reported in other human and rat tissues. IGF-II mRNA was also detected but at low abundance. Cell proliferation was stimulated in a dose-responsive manner by exogenous IGF-I (10-30 ng/ml). Addition of a monoclonal antibody against IGF-I to MCF-7 cells in serum-free medium caused an inhibition of cell proliferation, suggesting that endogenous locally produced IGF-I does play an autocrine/paracrine role in MCF-7 cell growth. Proliferation of MCF-7 cells was sensitive to oestradiol (10 nM) in the absence but not in the presence of the weakly oestrogenic pH indicator phenol red. Neither IGF-I secretion nor IGF-I mRNA synthesis, however, was affected by addition of oestradiol. Similarly, GH, dexamethasone or dexamethasone plus oestradiol had no effect on either parameter. These data indicate that MCF-7 cells synthesize, secrete and respond to IGF-I. The very low levels of ir-IGF-I produced and their apparent lack of hormonal modulation suggest, however, that further studies are required to establish whether IGF-I plays a major physiological role in growth and development of MCF-7 cells. PMID- 2590384 TI - Sex-steroid receptors in the diethylnitrosamine model of hepatocarcinogenesis: modifications by gonadal ablation and steroid replacement therapy. AB - The results of this study confirm our previous report of increased androgen receptor expression in livers of female SUAH Wistar rats during development of liver tumours induced by diethylnitrosamine (DENA). In adult female rats not treated with DENA, removal of the ovary increased liver androgen receptor levels but testosterone did not further enhance the androgen receptor status of ovariectomized rats. In normal adult males the testis and/or testosterone maintained high levels of androgen receptors but oestrogen reduced them in castrated rats. Oestrogen receptor levels were not significantly changed in either males or females by gonadectomy. Treatment of female rats with DENA for 10 and 16 weeks increased liver androgen receptors but oestrogen receptors were only reduced by 16 weeks of DENA treatment, whether the rats were intact or ovariectomized. Concentrations of liver androgen receptors were increased in intact and castrated male rats by 10 and 16 weeks of DENA treatment, an increase not seen in the previous experiments. Oestrogen appeared to inhibit both the increases in liver androgen receptor expression and liver tumour development in rats treated with the weakly carcinogenic dose of 10 weeks of DENA. However, the full carcinogenic dose of 16 weeks of DENA increased liver androgen receptors and decreased oestrogen receptors in female rats regardless of sex-steroid status. Development of malignant hepatocellular carcinoma (HCC) was associated with both an increase in liver androgen receptors and a decrease in oestrogen receptors. Maintenance of relatively high levels of liver oestrogen receptors appeared to protect the liver against development of HCC. PMID- 2590385 TI - Structural characteristics of growth hormone receptors on mouse 3T3 cells having different biological responses to growth hormone. AB - Cultured 3T3-F442A preadipocytes are able to undergo GH-promoted differentiation into adipocytes. The relationship between the structure and function of GH receptors on 3T3 cells (3T3-F442A preadipocytes, differentiated adipocytes and 3T3-C2 cells, which vary in susceptibility to adipose conversion or with respect to carbohydrate and lipid metabolism) was studied by the covalent cross-linking of 125I-labelled human (h) GH to intact cells with the bifunctional reagent disuccinimidyl suberate. When preadipocytes were cross-linked and analysed using sodium dodecylsulphate-polyacrylamide gel electrophoresis, a prominent 125I labelled hGH-receptor complex of Mr 130,000 was observed along with minor complexes (Mr 300,000, 230,000 and 60,000) on autoradiography. Non-reducing reducing two-dimensional gel electrophoresis revealed that the higher molecular weight complexes also contained the Mr 130,000 complex. Neuraminidase and tunicamycin treatment demonstrated that the GH receptor on F442A preadipocytes is a sialo-glycoprotein with N-linked carbohydrate chains. When the differentiated 3T3-F442A adipocytes and 3T3-C2 cells (a sub-line with no susceptibility to adipose conversion with GH) were examined in the same way as 3T3-F442A preadipocytes, no differences were observed in the specificity of GH binding and in the molecular size of the 125I-labelled hGH-receptor complexes and their glycosylation characteristics. This suggests that the structural characteristics of the GH receptor are closely related in each cell type, but that the hormonal signals produced after GH binding to the receptor may cause different effects according to the cell type. PMID- 2590386 TI - Both alpha- and beta-calcitonin gene-related peptides are present in plasma, cerebrospinal fluid and spinal cord in man. AB - The presence of both alpha- and beta-calcitonin gene-related peptide (CGRP) was demonstrated by oxidation and by CNBr cleavage in extracts of plasma, cerebrospinal fluid and spinal cord in man. This was achieved by the use of both CNBr cleavage and oxidation of the methionine residue present in the human beta CGRP molecule. This study demonstrates that around 50% of CGRP immunoreactivity in plasma, cerebrospinal fluid and spinal cord is not alpha-CGRP, but corresponds to beta-CGRP-like activity. Furthermore, experiments with CNBr also suggest the presence of another methionine-containing CGRP-like peptide in all three extracts. PMID- 2590387 TI - Relationship between the thyroidal and gonadal axes during the estrous cycle of ewes of different breeds and ages. AB - In order to define the patterns of TSH, T4, T3, rT3, GH and cortisol during the estrous cycle of sheep, pluriparous and primiparous ewes were synchronized with progestagen-impregnated pessaries (Veramix) at the start of the normal breeding season. After the pessaries were removed (day 0), daily blood sampling was carried out in cannulated ewes during the ovulatory cycle. Hormonal analyses of TSH, T4, T3, rT3, GH, cortisol, LH and progesterone (P) were performed by RIA. P and LH levels during the cycle were conform to the literature and were not different between the primiparous and pluriparous ewes of different breeds used in this study. Neither age nor breed influenced the hormone patterns. A significant negative correlation was found between TSH and P during the cycle, although the correlation between P and T4 was not significant; during the estrous period, low P levels were paralleled by high T4 levels, whereas the reverse was observed during the luteal phase. Higher T3 levels and T3/T4 ratios were observed during the luteal phase. No obvious pattern of rT3 and cortisol during the cycle was found. The GH concentration increased during the 17 days of the cycle. A positive correlation with P was calculated. During the estrous cycle obvious changes in thyroid hormones, GH and TSH occurred. However, this study shows no causal relationship between the thyroid and the gonadal axes. PMID- 2590388 TI - In vitro study of the effect of different ionophore antibiotics and of certain derivatives on rumen fermentation and on protein nitrogen degradation. AB - An in vitro study was carried out to evaluate the effect of different ionophore antibiotics and some of their derivatives on rumen fermentation and on the degradation of peanut meal nitrogen. The increase in the production of propionic acid at the expense of acetic acid, observed with lonomycin, nigericin, cationomycin and lysocellin, was identical to that noted with monensin. The decrease in methanogenesis observed in the presence of monensin was also found with cationomycin and lysocellin. With the exception of lysocellin, which greatly reduced protein degradation of peanut meal, and of nigericin, which had no effect on this parameter, the 2 other molecules presented the same action as monensin. The negative effect of monensin on microbial ammonia uptake was demonstrated with the same intensity in the presence of cationomycin; it was slightly higher with nigericin and particularly accentuated with lonomycin and lysocellin. Three ester derivatives of monensin (monensin acetate, monensin propionate and monensin butyrate) had a similar action to that of monensin on the orientation of rumen fermentations. The monensin isobutyrate derivative appeared to be more active than monensin and only weakly altered microbial ammonia uptake. The oxolonomycin and hydroxolonomycin derivatives behaved identically to lonomycin with respect to microbial metabolism and protein nitrogen degradation. Unlike the molecules from which they derive, the deacylated cationomycin and nigericic acid had no effect on the orientation of rumen fermentations. Of the compounds tested and presenting a potential 'growth-promoting action' at least comparable to that of monensin, and which demonstrated lower toxicity on mice, three molecules (oxolonomycin, lysocellin and cationomycin) appeared to present a zootechnical interest as feed additives for growing cattle. PMID- 2590389 TI - Photoperiod and parturition period in isolated or paired rats: influence of sight deprivation and social conditions. AB - Time of delivery was studied in normal (N) or enucleated (E) rats. Isolated (1/cage) at mating (day 1 of gestation), they were all anaesthetized on day 8 and some of them were then blinded. After anaesthesia, they were kept either alone (N and E) or in homogeneous (NN and EE) and heterogeneous (NE) pairs either under a 12L-12D or a 2L-22D light-dark (LD) cycle. Activity, monitored throughout the rest of pregnancy in 2 homogeneous (NN and EE) and heterogeneous (NE) pairs of rats, kept a marked circadian rhythm under each light regimen. Birth distributions differed according to LD cycle in normal (N or NN) but not in enucleated (E and EE) rats. Under the 12L-12D regimen, parturitions of N and E rats were divided into 2 parts, the majority occurred on the afternoon of day 22 before 21:00 h, the remainder were observed after 6:00 h on day 23. Under the 2L 22D regimen, N rats gave birth over one period, mainly on day 23, whereas E rats had the same birth distribution as those subjected to the 12L-12D LD cycle. In heterogeneous pairs of rats (NE), birth times were affected by photoperiod; under the 2L-22D regimen it was intermediate between those of homogeneous pairs (NN and EE). These results indicate that the eyes were the first link of the nervous chain by which photoperiod influenced birth time. Social conditions may also modulate the photodependent mechanism in ways which remain to be determined. PMID- 2590390 TI - A quantitative histological study of adrenal development during the perinatal period in intact and hypophysectomized pigs. AB - Adrenal growth was studied between D70 of gestation (D0: day of mating) and D6 after birth in 33 fetuses and 11 new-born pigs of the Large White breed. Volume, height and mean surface, were estimated by zone, as well as cell number, cell size and nucleocytoplasmic ratio. The volume increased exponentially. In the cortex it was 4.0 mm3, 7.2 mm3, 10.5 mm3, 33.6 mm3, 55.3 mm3 at D70, D94, D106, D113 and D1-D6, respectively, after birth. In the medulla, the volume was 4.0 mm3, 6.3 mm3, 6.9 mm3, 9.6 mm3 and 20.6 mm3 at the same stages. This evolution was due to predominant longitudinal stretching between D94 and D106, then thickening, as shown by the relative variations of the height and the surface. The growth of the cortex corresponded to hyperplasia associated with hypertrophy after D110. In the medulla, hyperplasia predominated until D110; this was followed by hypertrophic phase. Twelve fetuses hypophysectomized at D44 or at D55 were recovered at D94, D106 and D112 at least 50 days after surgery. Hypophysectomy did not affect medullar development (volume and number of cells) but inhibited very significantly the growth of the cortical zone, particularly that of the fasciculata. PMID- 2590391 TI - Relationship between lipid parameters and the occurrence and severity of lesions in the heart: a study on rats fed low erucic acid rapeseed oil. AB - Fifty-six male Wistar SPF rats were fed a diet containing low erucic acid rapeseed (LEAR) oil (15% by weight) as the only source of lipids for 18 wk. Lipid parameters (fatty acid composition and contents of lipid classes) and the occurrence and severity of focal lesions were both determined on the heart of each animal. Four groups were constituted according to the severity of cardiac lesions. Statistical analyses were applied to the data to find a relationship between the lipid parameters and the severity of heart lesions. None of the measured parameters (heart contents of neutral lipids, total phospholipids, phosphatidylcholine, phosphatidylethanolamine, diphosphatidylglycerol, sphingomyelin and fatty acid composition of each phospholipid class) appeared to be related with the grading of the lesions. Therefore, we failed to find a direct support for the assumption that heart lesions, induced by LEAR oil, are mediated by changes in the lipid and/or fatty acid composition of heart membranes. However, this hypothesis can not be discarded. PMID- 2590392 TI - Peripheral plasma progesterone concentration in zebu (Bos indicus) cows during pregnancy. AB - Plasma progesterone concentrations were determined weekly during gestation averaging 283 +/- 2 d in Ethiopian zebu (Bos indicus) cows. Mean progesterone levels increased from 0.2 +/- 0.1 ng/ml at oestrus (service) to 3.1 +/- 1.6 ng/ml on d 7 and 8.1 +/- 2.1 ng/ml on d 21. Progesterone levels remained elevated throughout pregnancy. Hormone concentration differed significantly between cows (P less than 0.001) and with the wk of pregnancy (P less than 0.05); it tended to be higher during the last trimester of pregnancy. Mean levels dropped sharply to below 1 ng/ml during the last wk of pregnancy with considerable variation (C.V. = 39 to 63%) among cows. These data indicate that pregnancy in Ethiopian zebu cows can be reliably diagnosed by determining circulatory plasma progesterone levels. PMID- 2590393 TI - [Seasonal evolution of blood levels of thyroxine and triiodothyronine in the post pubertal bull in France and Iraq. Concomitant variations of LH and testosterone]. AB - An inquiry was conducted in 2 performance testing stations, A and B located in France and Iraq, respectively. In both stations, at solstice and equinox, thirty 15 month-old Holstein bulls were blood sampled for plasma LH, testosterone, thyroxine and triiodothyronine determination. For LH, no coherent seasonal effect was found. As regards testosterone, maximal mean values were obtained in December in both stations (3.4 ng/ml). In A as well as in B, thyroxine peaked in December reaching 64.6 ng/ml and 77.8 ng/ml, respectively, and falling down to 49.4 ng/ml and 65.6 ng/ml, respectively in June. The difference was significant for A (P less than 0.001). For T3, the fall from December (1.42 ng/ml in A and 1.68 ng/ml in B) to June (1.09 ng/ml in A and 1.26 ng/ml in B) resulted in about the same relative value and was significant (P less than 0.005) in both stations. The detrimental effect of high temperatures on semen quality does not seem to be mediated by an alternation of thyroid function. PMID- 2590394 TI - Structure and regulation of the avian gene for fatty acid synthase. AB - Starvation, glucagon and cyclic AMP inhibit, and refeeding starved animals and insulin or IGF-I plus triiodothyronine stimulate accumulation of FAS and its mRNA in liver; transcription is the primary regulated step. In the uropygial gland, differentiation of basal cells into mature sebocytes is accompanied by the accumulation of large amounts of FAS and its mRNA. By analogy with liver, transcription is likely to be the regulated step, but direct experimental evidence for this hypothesis is lacking. FAS mRNA is a unique gene and is probably more than 100 kb in length. The FAS gene of goose and duck is transcribed into two mature mRNAs of about 10,800 and 12,200 nucleotides. The 3' untranslated regions of the FAS mRNAs contain an unusual polypyrimidine tract which, at the mRNA level at least, appears unrelated to regulation of gene expression. Polypyrimidine tracts similar in sequence to that in the FAS gene are found in about 20 different parts of the genome. All of the fragments which contain these tracts are hypermethylated. The next stage of this investigation will involve identification of cis-acting sequence elements in the FAS gene which specify responses to diet, hormones and tissue-specific regulatory factors. Isolation and characterization of the 5'-ends of the cDNA and the gene are underway. PMID- 2590395 TI - Acrosomal status quantitation in human sperm. AB - Acceptable methods are currently available for the rapid quantitation of acrosomal status in human sperm. Application of these methods to human sperm has led to the concept that spontaneous acrosomal loss occurs infrequently during capacitation. Induced loss occurs following sperm exposure to human follicular fluid, to zonae- or cumulus-enclosed eggs, or to calcium ionophores or other agents that modulate intracellular calcium levels. Acrosomal status quantitation may be helpful in sperm morphologic characterization or in evaluating cryodamage but has not yet been established in fertility potential measurement. PMID- 2590396 TI - Levels of interleukin-2 receptor in serum of patients during the menstrual cycle and following embryo/gamete transfer. AB - In an attempt to establish whether nidation elicits a measureable systemic immunologic response in vivo, levels of interleukin-2 receptor (IL-2R) have been determined in serum drawn from 34 pregnant patients (IUP) immediately before embryo/gamete transfer, and 7 and 14 days later. For comparison, these same values were determined for 41 subjects who did not conceive, and for 18 who spontaneously aborted (SAB) during the first trimester of gestation. Serum IL-2R values were near 320 U/ml and did not differ between days within outcomes, or within days between outcomes. Furthermore, levels of IL-2R and beta-hCG in serum were not interrelated on days 7 or 14 of pregnancy (SAB or IUP). Serum IL-2R levels did not change during the menstrual cycle. The present results appear to traverse presumptive elements of existing hypotheses of "placental immunotropism." PMID- 2590397 TI - Attempts to identify trophoblast in peripheral blood during pregnancy using monoclonal antibody H315. AB - In view of its potential importance in antenatal diagnosis of genetic disease, we have used flow cytometry to attempt to enumerate trophoblast cells in the peripheral blood of pregnant females. As a trophoblast marker we have used the monoclonal antibody (MAB) H315, which reacts with placental-type alkaline phosphatase (PLAP) associated with the cell-membrane of the syncytiotrophoblast. We analyzed blood leucocytes from 62 pregnant females between 6 and 22 weeks' gestation, 26 nonpregnant females, and 21 males. Overall, we detected more H315+ cells in pregnant than in nonpregnant female blood but, because of the wide variation in both groups, we found no statistically significant difference between them. We were unable to detect H315+ cells in 25% of pregnant females within the resolution of the technique. There was, in contrast, a significant difference between the number of H315+ cells in pregnant females and males. Because we were unable to demonstrate other trophoblast markers on H315+ cells isolated from maternal peripheral blood, the origin of these cells is unclear. This implies that these cells may be an unsuitable source of material for antenatal diagnosis. PMID- 2590398 TI - Functional heterogeneity of sialic acid binding agglutinins of rat uteri towards in vitro lymphocyte transformation. AB - The sialic acid binding agglutinins (SAS) are purified from three different stages (proestrus [P], estrus [E], diestrus [D]) of rat uterine homogenate. All three proteins are capable of inhibiting the in vitro phytohemagglutinin (PHA) induced blastogenic response of lymphocytes and thymocytes as manifested by inhibition of 3H-thymidine incorporation into cells. The lymphocytes isolated from pregnant female rats were found to be more susceptible to inhibition. In resting lymphocyte cultures (RLC), however, the P- and E-SAS proteins acted differently from the D-SAS by stimulating lymphocyte proliferation in the cultures initiated from normal rat lymphocytes. At the same dose these proteins were inhibitory to the RLC, where cultured lymphocytes were isolated from the pregnant female. Reverse hemolytic plaque formation assay results also indicated functional heterogeneity between these proteins. P-SAS induced a potent polyclonal activation of the B cell, whereas E- and D-SAS did not show much activation. SAS proteins do not have any complement-like activity. These results, corroborated by cell viability count and 51Cr uptake tests, suggest that D-SAS has genuine lymphoblastogenesis-suppressive properties whereas P- and E-SAS induced suppression in the presence of PHA is probably due to an increased cell density-dependent cytotoxicity. PMID- 2590399 TI - Pulmonary complications in burn patients resuscitated with a low-volume colloid solution. AB - The occurrence of the adult respiratory distress syndrome (ARDS) and pneumonia was assessed in 482 patients with severe burns, but without evidence of inhalation injury. The patients were resuscitated during the burn shock period with a low-volume formula consisting mainly of plasma. The incidence of ARDS was 2.5 per cent for the entire burn population, and 9.4 per cent for 65 patients with burns covering more than 50 per cent of the body surface area. The general incidence of pneumonia was 4.4 per cent but was 12.5 per cent for the 65 patients with the extensive burns. These incidences were compared with other studies, and a pathophysiological explanation has been offered to explain differences in the frequency of pulmonary complications. The present review indicates that resuscitation with a low-volume formula consisting mainly of colloids can act as prophylaxis for reducing the incidence of ARDS and pneumonia. PMID- 2590400 TI - Contact burns in children. AB - Forty-seven children under the age of 5 years admitted for contact burns into the Burns Unit of the Birmingham Accident Hospital during the period 1981-88 were reviewed. Contact burns formed only 3.93 per cent of all the thermal injuries seen in this age group for the same period. Most of the children were between 1 and 2 years of age and the hands and face were more frequently burned. The hot electric iron was the commonest cause of burns in the study. Although the sizes of the burns were generally small, the potential scarring and disability were recognized and this influenced the management. The prevention of contact burns from hot electric irons has been discussed and the need to look out for non accidental injuries emphasized. PMID- 2590401 TI - Effect of autografting on the diameter of collagen fibrils in human postburn wounds. AB - The effect of skin grafts on the size of collagen fibrils in autografted human burn wounds was examined. In autografted burn wounds, the mean (+/- standard deviation) diameter of collagen fibrils was 61.16 +/- 15.18 nm, against 39.77 +/- 6.51 nm in ungrafted burn wounds. This result indicates that autografts (0.1 mm thick) promote the maturation of collagen in burn wounds. PMID- 2590402 TI - Burn injuries in the Jeddah area of Saudi Arabia: a study of 319 cases. AB - Three hundred and nineteen patients with different types of burns were studied at King Fahd Hospital, Jeddah, Saudi Arabia over a 2-year period (December, 1985 to December, 1987). Scalding was the most common cause (56.4 per cent) of burn injuries compared with 41.4 per cent of patients who sustained flame injury; 84.6 per cent of the thermal injuries occurred at home, with children (less than or equal to 18 years of age) being affected most frequently (61.8 per cent). The overall mortality was 9.4 per cent. PMID- 2590403 TI - Mortality from burns in Kuwait. AB - There were 96 deaths among 1433 burns patients admitted to the Plastic Surgery and Burns Unit at Ibn Sina Hospital and Plastic Surgery Unit at Mubarak Al-Kabeer Hospital from January 1982 to December 1987. This represents an overall mortality of 6.7 per cent; 74 per cent of the patients who died had sustained more than 50 per cent body surface area (BSA) burns. A large number of deaths occurred in two age groups, 0-5 years (21 deaths) and 21-30 years (24 deaths). The male to female ratio of burn-induced deaths was 1.18:1. Flame burns due to domestic accidents were the aetiological factors in the majority of patients; 84 (87.5 per cent) of those who died sustained flame burns, although flame burns were only responsible for 46.6 per cent of all burns cases admitted. The mean survival period was 16.8 days postburn, the longest period being 79 days for a patient with 60 per cent BSA burns. Forty-seven patients (49.9 per cent) died of septicaemia which, with its related complications, remains the most important cause of death in our burns patients. PMID- 2590404 TI - Blood volume changes of the anaesthetized rat to a large burn or mock burn injury measured using a continuous measuring circuit. AB - A scald burn injury of 40-60 per cent body surface area was applied to the sodium pentobarbitone anaesthetized rat. The cardiac output of the burn injury rats fell from 39.5 +/- 2.1 to 27.7 +/- 1.5 ml/min (P less than 0.001) while heart rate, mean arterial blood pressure and central venous pressures were little changed but the total peripheral resistance rose significantly. Cardiovascular function was unchanged in control, mock-burned rats. The blood volume was measured continuously using an extracorporeal circuit and was observed to fall significantly by 0.78 +/- 0.36 ml in 5 min (P less than 0.05) and 1.65 +/- 0.38 ml in 60 min (P less than 0.001) after burn injury. The falls in blood volume and cardiac output were virtually simultaneous, and had occurred by 5 min. It is proposed however that this fall in blood volume is not sufficient to cause the observed changes in cardiac output and that additional factors such as cardiac impairment may be responsible for these changes postburn. PMID- 2590405 TI - Use of the lithotripter in the burned patient as an aid to mobilization. AB - A young lady with extensive burns and multiple fractures developed renal calculi, and repeated attacks of colic, accompanied by nausea and vomiting which delayed her hyperalimentation and mobilization. The insertion of J stents stopped these episodes of colic and the stones were eliminated by extracorporeal lithotripsy before the burn wounds were healed. Urinary infections cleared and rehabilitation thereafter was uncomplicated. PMID- 2590406 TI - Experience of reverse medial arm flaps in the reconstruction of burned elbow scar contractures. AB - There are many methods to correct scar contractures in the elbow region after burn injury, including Z-plasty, Y-V or rectangular flaps, local or distant fasciocutaneous flaps, muscle or myocutaneous flaps, free flaps, tissue expanders and non-surgical orthotics. Among these, the reverse medial arm island flap, based on the recurrent ulnar artery, has proved to be a convenient local fasciocutaneous flap for elbow scar reconstruction. In the past 2 years, 12 reverse medial arm flaps were used in 11 patients. The results are satisfactory. Two complications, one partial flap necrosis, another ulnar nerve compression, were noted. Our clinical experience with this flap encourages us to use it for burn elbow reconstruction in the future. The advantages and disadvantages are discussed. PMID- 2590407 TI - Novel method of skin substitution in plastic surgery. AB - A skin substitute has been developed by growing a large number of epidermal cells from a skin biopsy (1 cm2) taken from burn patients. In tissue culture the cells divide and grow quickly to form a monolayer sheet. These sheets were then trypsinized into free cells, which were applied onto the wounds of two patients suffering from full skin thickness burns. The cultured epithelial grafts continued to thicken and expand successfully until they became confluent with the surrounding epidermis. All the wounds healed successfully. Clinically and histologically these cultured epithelial autografts were proven to be of the same quality as split thickness skin grafts. PMID- 2590408 TI - Amniotic membrane as a biological dressing in the management of burns. AB - This report details observations in 90 patients with dermal depth burns treated using amniotic membrane. The patients were divided into three subgroups: superficial dermal, intermediate dermal and deep dermal burns diagnosed clinically. All patients were dressed with amniotic membrane which was changed daily. The amniotic membrane relieved the discomfort of dressing changes, postoperative pain and oozing and allowed rapid epithelialization and early healing in superficial and intermediate depth dermal burns. In deep dermal burns the membrane was dissolved because of slough in the burn wound. After removal of the slough the amniotic membrane helped in rapid regeneration of epithelium and early healing. PMID- 2590409 TI - Burn wound infection. PMID- 2590410 TI - Practical considerations for patient investigation using a high field (1.5T) magnetic resonance system. PMID- 2590412 TI - Peripelvic extravasation during i.v.u. due to compression. PMID- 2590411 TI - Quantification of bone density and mineral content. AB - To summarise, densitometry is used for measuring trabecular bone sites and morphometry for measuring cortical bone sites. Simple morphometry is still a very useful method of estimating bone loss. In sequential studies sophisticated techniques are now available, linked with computer analysis. PMID- 2590413 TI - Important issues on Korner statistics. PMID- 2590414 TI - Hit or miss--is perfection achievable in radiotherapy? PMID- 2590415 TI - Regional distribution centres--the Huddersfield experience. PMID- 2590416 TI - The use of project work in the psychological aspects of patient care. PMID- 2590417 TI - Needle localisation of occult breast lesions. PMID- 2590418 TI - Defecography--a new technique for the study of disorders of defecation. PMID- 2590419 TI - The barium enema: the role of the radiographer. PMID- 2590420 TI - The hazards of using ionising radiation for non-malignant conditions--a case study. PMID- 2590421 TI - An estimation of doses received by patients in a diagnostic x-ray department. AB - This article describes a method of estimating the effective dose equivalent received by patients undergoing (non-fluoroscopic) diagnostic x-ray examinations. This allows those clinically or physically directing exposures to comply with the requirement, item 3, in the core knowledge contained in the schedule of the health and safety document number 778. The method described can be carried out without the use of expensive equipment or time consuming procedures and is based on the data contained in the publication NRPB R200. This method does not conflict with that described by Shrimpton in Radiography Today but is an alternative approach. PMID- 2590422 TI - Developing a radiology computer system. PMID- 2590423 TI - Viewpoint of an out-patient manager. AB - To provide a truly excellent service to the customer all those involved with out patients must work together. All heads of departments must demonstrate the essential aspects of good management, not only within their own departments but also between departments. Only by planning, organising and communicating can we achieve a controlled response to the demands of the consumer. For this to become a reality there must be openness, a commitment to learn from each other and a willingness to change. PMID- 2590424 TI - The application of a marking scheme to psychology projects by student radiographers. AB - A study was initiated to assess the reliability of a marking scheme for research projects on the psychological aspects of patient care. The marking scheme was applied to ten projects by three markers and the Spearman Rank correlation coefficient (rho) was determined for the three pairings of markers. The t-test was applied to the means of scores awarded by the pairs of markers in order to establish the statistical significance of the variation between markers. The Kendall coefficient of concordance was used to measure the relation among the three rankings of scores. The Spearman Rank coefficient and the t-test showed (at p less than 0.05 and p less than 0.10 respectively) that there was a statistically significant difference between one pairing of the scores from the three markers. The Kendall coefficient of concordance was found to be 0.73 with quite a high level of agreement between the three markers, but there were some discrepancies in the rankings. If we take into consideration the individual markers' experiences in assessing such projects, we find that the pair with the most disparity in experience proved to be the pair whose scoring differed significantly. A modified marking scheme was developed as the basis for further research. PMID- 2590425 TI - Diagnosis of dysbaric pathology. PMID- 2590426 TI - Localising non-palpable lesions within the breast using the needle and wire technique. PMID- 2590428 TI - Educational situations in clinical settings. PMID- 2590429 TI - The Welbeck memorial lecture 1988. Radiology and breast cancer. PMID- 2590427 TI - The role of the radiographer in the treatment planning of tumours. PMID- 2590430 TI - Dynamic imaging of defaecation--the video proctogram. PMID- 2590431 TI - Performance indicators in the NHS. PMID- 2590433 TI - The uncertain effects of small radiation doses. PMID- 2590434 TI - The problems of working in Saudi Arabia. PMID- 2590432 TI - Issues on NHS reform. PMID- 2590435 TI - Videofluoroscopy of dysphagia patients. PMID- 2590436 TI - Direct coronal CT of the neck. AB - A simple apparatus for producing contiguous, direct, coronal, computed tomography (CT) slices of the neck is described. The apparatus can be applied to most body scanners with slight modification to its attachment. An example of a direct coronal scan is illustrated. PMID- 2590437 TI - The need for more patient counselling. PMID- 2590438 TI - Lymphoedema due to lymphatic hyperplasia: a case report. AB - An unusual case of generalised lymphoedema is described. The congenital nature of the lymphatic anomaly and the significance of its lymphographic appearance are discussed. PMID- 2590439 TI - A practical guide to mammography training. PMID- 2590440 TI - The recruitment problem. PMID- 2590441 TI - Radiography training. PMID- 2590442 TI - A question of public trust. PMID- 2590443 TI - Use of CT scanning to optimise the localisation procedure for breast radiotherapy. AB - The continually improving technology in breast screening is now allowing diagnosis of patients with early stage breast cancer who would otherwise not have presented for many years. Surgical techniques are directed to achieving the best possible cosmetic result following the surgery. Radiotherapy treatment machines are becoming more complex and sophisticated in design and capability. Why, therefore, should we not employ today's technology for the localisation process? This is a report of our experience in using CT scanning to localise the treatment volumes for breast patients over a period of one year. A comparison between marking patients by palpation and the use of CT scanning has prevented a number of patients being under-treated and has enabled the reduction of lung volume included in the treatment volume for other patients. It has also proved a valuable aid in the decision to use electron fields for mastectomy patients. Other means of localising the treatment volumes are considered in the light of our experiences. PMID- 2590444 TI - The special needs of cancer patients' relatives. AB - Some relatives of cancer patients also suffer greatly from depression and anxiety but are less likely to be treated for it. It is vitally important to provide constant emotional support to help them in their roles as carers. PMID- 2590445 TI - The radiographer as counsellor. PMID- 2590446 TI - The extended working day. PMID- 2590447 TI - Radiation regulations. PMID- 2590448 TI - A practising faith--Christianity. PMID- 2590449 TI - Bone mineral analysis using a Picker CT scanner. PMID- 2590450 TI - Idealism and realism in patient care during radiotherapy treatment. AB - Previous research has demonstrated that typification of patients by health workers is inevitable even when these workers aspire to a concept of treating each patient as an individual. This study aimed to establish how six therapy radiographers, working in three different settings, typified their cancer patients and how this related to their concept of role and the environment in which they worked. The techniques used were ethnographic, non-directive interview techniques and naturalistic observation. There are interesting variations and similarities in how the individuals perceived their working role and environment and in their perception of patients. The typifications of patients by the therapy radiographers studied are related to and reflect the radiographers' concerns or stresses. They relate to the issues of information giving and receiving, control of the radiographer-patient relationship, how to cope with patient dependency and how this interacts with their own ideals and impression management. Some also reflect the problems experienced in working relationships, in particular balancing their own ideals with the reality of their working situation. PMID- 2590452 TI - The HDCR: demand and supply. AB - This article is intended to indicate that, despite the difficulties which exist, the revised format of the HDCR is a success. The major area of concern has undoubtedly been module F. Up to 21 July 1988, over 100 initial submissions had been approved by the board of studies and about 20 successfully completed dissertations were held in the college library. In future, the title of the dissertation will accompany the publication of the names of those successful in all modules of the HDCR. It is intended that those who submit outstanding dissertations will be invited to present them at the annual conference or teachers and superintendents' seminars. These various measures will publicise work which has been done and which may be of interest to those undertaking postgraduate research degrees. Thus the college and the profession will be seen to own a body of scientific and professional knowledge. Consequently, it is now only a matter of time before the college is able to approach higher education institutions and validating bodies to argue that the qualification represents an educational and professional standing that justifies radiographers access to advanced degree courses. Thus the Higher Diploma of the College of Radiographers will have achieved its justified status. PMID- 2590451 TI - Direct coronal imaging in computed tomography of the lumbar spine. PMID- 2590453 TI - Postrad open learning. AB - When correctly presented, organised and funded, open learning has a valuable contribution to make to any radiographer's educational aspirations, and is already proving its worth both for HDCR and other areas of study. Once used to the method, students settle well and are successful and motivated. PMID- 2590454 TI - In praise of Saudi Arabia. PMID- 2590455 TI - Further analysis on diagnostic and therapy discrepancies. PMID- 2590456 TI - Christianity. PMID- 2590457 TI - AIDS in nuclear medicine. PMID- 2590458 TI - Funding a special breed of student. PMID- 2590459 TI - A practising faith--Islam. PMID- 2590460 TI - Effects of 2-hydroxypropyl-beta-cyclodextrin on the aqueous solubility of drugs and transdermal delivery of 17 beta-estradiol. AB - The effect of 2-hydroxypropyl-beta-cyclodextrin (2-HPCD) on the aqueous solubility of 18 drugs possessing different physiochemical properties was investigated. The largest increase in aqueous solubility was obtained with very lipophilic drugs with low aqueous solubility and the enhancement was larger at low temperature than at high temperature. In many cases a linear relationship exists between the drug solubility and the 2-HPCD concentration. Ionization of a drug molecule enhanced the solubility effects of 2-HPCD, resulting in greater aqueous solubility than if either method was used by itself. 2-HPCD was found to be an effective transdermal permeability enhancer. PMID- 2590461 TI - Determination of alfentanil in serum by radioimmunoassay or capillary column gas liquid chromatography. A comparison of the assays. AB - In view of recent controversies about the specificity and accuracy of radioimmunoassays (RIA) for morphine and alfentanil, we assessed the validity of an RIA for alfentanil by comparing it with a novel capillary column gas-liquid chromatographic (GLC) assay. The coefficients of variation for eight determinations of alfentanil in plasma or serum were approximately 2% at 2, 20, and 400 ng/ml with both assays. The assay comparison was done using 85 serum samples from patients given intravenous alfentanil. There was an excellent correlation between the assay results obtained by RIA and by GLC in the range of 10-1 825 ng/ml. The two assays can therefore be used interchangeably in pharmacokinetic studies. PMID- 2590462 TI - Interference by an endogenous substance in the HPLC assay of dobutamine in dog plasma. Comparison study on rat, dog, monkey, and human plasma. PMID- 2590463 TI - Symposium on thermodynamics in pharmaceutics--a tool in drug development. Stockholm, March 1-3, 1989. 27th international symposium. Abstracts. PMID- 2590464 TI - Intracellular activity of lysosomal glucosylceramidase measured with 4 nonylumbelliferyl beta-glucoside. AB - Enzymatic activity of lysosomal glucosyl-ceramidase was determined in intact murine hybridoma and macrophage cells with the synthetic substrate nonylumbeliferyl-beta-glucoside (NUG). The substrate was applied as complex with bovine serum albumin (two binding sites, Kd 2.2 +/- 0.3 microM). The transport of the artificial substrate from medium to the enzyme was explored by measurements of substrate concentrations in cellular membranes and of endocytosis rate relative to substrate hydrolysis. The results indicated that, after enrichment in the plasma membrane, the substrate is mainly transported by simple diffusion. Release of nonylumberlliferone monitored fluorimetrically after disintegration of the cells in borate buffer containing Triton X-100 at pH 9.5 showed that 10(8) cells of both cell lines hydrolysed 1-1.5 nmol substrate/min at a total concentration of 0.1 mM NUG in the medium. Substrate hydrolysis was prevented by preincubating the cells with conduritol B epoxide (CBE), a specific active site directed inhibitor of lysosomal glucosylceramidase. The substrate concentration at the site of the enzyme and maximal activity were evaluated by the inhibiting effect of the substrate on the inactivation rate by conduritol B epoxide. The rate of inhibitor uptake measured with bromo-[3H]conduritol B epoxide was shown to be not rate-limiting for the inactivation reaction. The molar concentration of the enzyme was determined by labeling with bromo-[3H]conduritol B epoxide. Comparison of the maximal intracellular activity with that of the enzyme after disintegration and activation by taurocholate showed a 20-fold lower activity in the native environment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590465 TI - The primary structure of electric ray hemoglobin (Torpedo marmorata). Bohr effect and phosphate interaction. AB - The blood of the Electric Ray contains a number of hemoglobin components. The primary structures of the alpha- and beta-chains of the main components are presented. These chains were purified by high-performance liquid chromatography, using a new buffer system. The alpha-chains consist of 141 residues, and the beta chains of 142 residues; both are unblocked. The phylogenetic distances from human alpha- and beta-chains are 55% and 64% amino-acid exchanges, respectively. The relationship between primary structure and the lack of both a Bohr effect and any effector affinity is discussed, and interpreted on a molecular level with reference to the sequence presented. For the Bohr effect, the mutation beta 89 Asp----Lys is significant, while the mutations beta 2 His----Ser, beta 82 Lys--- Asn and beta 142 His----Cys are important for the lack of effector affinity. PMID- 2590467 TI - The N-terminal amino-acid sequence of human placental sterylsulfatase. AB - The N-terminus of the recently isolated sterylsulfatase of human placental cellular membranes was sequenced. According to our results, the enzyme preparation proved to be homogeneous at least with respect to this part of the polypeptide chain; the n-terminal sequence of the sulfatase previously proposed by others, however, had to be revised partially. PMID- 2590466 TI - Comparison of insect hemoglobins (Erythrocruorins) from Chironomus thummi thummi and Chironomus thummi piger (Diptera). The primary structure of the monomeric hemoglobin CTP III. AB - The monomeric hemoglobin fractions of Chironomus thummi thummi (CTT) and Chironomus thummi piger (CTP) differ in the ratio of their components. The determination of the primary structure of the component CTP III was achieved by automatic Edman degradation of the native chain, the tryptic peptides and the C terminal fragment, obtained by cleavage at the single tryptophan residue. It revealed two chains in the ratio 1:1 which share the ambiguity threonine/isoleucine in position 57 with CTT III. Whereas one chain is identical to the CTT III hemoglobin, the other differs in having isoleucine in position 105 and alanine in position 134. The CTP monomeric hemoglobin fraction comprises 8% of a component (CTP IV A) with a more negative charge than CTT IV but with an identical sequence up to position 44. This study reveals a very high polymorphism within Chironomus species and points out the need for more data at the gene level in order to provide better understanding of this striking phenomenon. PMID- 2590468 TI - High-frequency antigens of human erythrocyte membrane sialoglycoproteins. VI. Monoclonal antibodies reacting with the N-terminal domain of glycophorin C. AB - The epitopes of seven mouse monoclonal antibodies which are related to the Gerbich blood group system were investigated. BRIC4, BRIC10, GERO and MR4-130 have been published earlier. The three others (APO1, APO2, APO3) were prepared by immunization with normal human erythrocytes and detected by screening with red blood cells that lack glycophorins C and D. Using immunoblotting and hemagglutination inhibition assays, the epitopes for all antibodies were found to be located on glycophorin C. Hemagglutination inhibition experiments with peptides and chemically modified glycophorins revealed that MR4-130, GERO, BRIC10 and APO2 are all directed against identical or rather similar epitopes comprising the N-terminal three or four residues of glycophorin C. Modification of the N terminal methionine residue or release of sialic acid attached to oligosaccharide(s) at the third and/or fourth position(s) destroyed all these antigens. The epitope of APO3 was found to comprise glutamic acid17 and/or aspartic acid19 as well as the oligosaccharide attached to serine15. The antigens of BRIC4 and APO1 were found to be located within the residues 2-21 and to comprise sialic acid attached to O-glycosidically linked oligosaccharide(s). However, these epitopes could not be elucidated further. Radio-iodinated MR4-130 bound to 39,000 receptor sites per normal red blood cell. Binding of the labelled antibody was completely inhibited by unlabelled MR4-130, BRIC10, APO2 and GERO. APO1 caused partial inhibition suggesting that it is directed against an adjacent site. BRIC4, APO3 and anti-Ge3 did not inhibit the binding of labelled MR4-130 to any significant extent. PMID- 2590469 TI - Structural analysis of glycophorin A from Miltenberger class VIII erythrocytes. AB - The major human erythrocyte membrane sialoglycoprotein (glycophorin A or MN glycoprotein) was purified from the erythrocytes of two individuals heterozygous for the Mi-VIII gene in the Miltenberger subsystem of the MNSs blood-group system. The complete structure of a tryptic glycopetide from glycophorin A comprising the residues 40-61 was deduced from automated and manual sequence analyses. The Mi-VIII-specific glycophorin A was found to exhibit an arginine--- threonine exchange at position 49. The threonine residue was found to be glycosylated. Hemagglutination and hemagglutination inhibition assays demonstrated that one of the Mi-VIII-characteristic antigenic determinants (Anek) is located within the residues 40-61 of glycophorin A. Furthermore, erythrocytes from the two Mi-VIII heterozygotes reacted only weakly with anti-EnaKTsera, suggesting that the Mi-VIII-specific glycophorin A does not express the EnaKT antigen that is located within the positions 46-56 of normal glycophorin A. Our data suggest that the Mi-VIII-specific glycophorin A represents the evolutionary link between normal glycophorin A and the Mi-VIII-specific molecule which exhibits arginine----threonine and tyrosine----serine exchanges at the positions 49 and 52, respectively. Our data also provide an explanation for the close serological similarity between Mi-VII and Mi-VIII erythrocytes. PMID- 2590471 TI - Women's health in the Third World: the impact of unwanted pregnancy. Proceedings of the Second Christopher Tietze International Symposium. Rio de Janeiro, October, 1988. PMID- 2590470 TI - Hemoglobins from bats (Myotis myotis and Rousettus aegyptiacus): a possible example of molecular adaptation to different physiological requirements. AB - The functional properties of the hemoglobin systems from two different species of bat i.e. Rousettus aegyptiacus and Myotis myotis have been studied as a function of chloride, polyphosphates, pH and temperature. Apart from overall similarities shared with most mammalian hemoglobins, the two systems show significant differences with respect to the effect of chloride and temperature sensitivity. These findings have been related to the different physiological needs of the two species. PMID- 2590472 TI - The Christopher Tietze International Symposium: an overview. PMID- 2590473 TI - Commentary on women's reproductive health: means or end? PMID- 2590474 TI - Commentary on women-centered reproductive health services. AB - From women's perspectives, the primary principles of a reproductive health framework in the developing world are as follows: Family planning is a basic human right to which all human beings are entitled. Provision of family planning services must be comprehensive, including safe and low cost methods, freedom of choice about both contraception and pregnancy termination, timely and honest information, privacy and confidentiality, individual needs assessment, and counseling of women, men or the couple. Wide contraceptive choice requires more research on methods that are less invasive of women's anatomy and physiology and more supportive of women's control of their own bodies. These parameters of quality care in family planning must be centered on women's needs, desires and expectations. The concept of conscious contraception implies an attitude of conscious sexuality. When a woman accepts that sexual gratification independent of reproduction is a legitimate right, she is better prepared to engage in the pursuit of her own health and happiness. If family planning programs do not include sexuality as a key issue to discuss with clients, all long-term strategies will fall short in modifying people's attitudes, especially women's reluctance to contracept. Sexual and reproductive health includes emotional health. As Dr. Sai points out, the effects of underdevelopment and poverty strike women in dramatic ways, and quite often all the pressures to which they are exposed lead to precarious emotional health. They become victims of violence and repeat the cycle of violence with their children. We, as advocates of sexual and reproductive rights, must also consider the psychological and emotional implications of sexuality and reproduction, and learn to deal with them in our clinics and services.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590475 TI - Commentary on a community-based approach to reproductive health care. Society for Education, Action and Research in Community Health Team. AB - Reproductive care needs to be broadened beyond maternity care and family planning to include care for gynecological and sexual problems, safe abortion services, and sex and reproductive health education. Our epidemiologic study of rural women has shown a very high prevalence of gynecological diseases. We tried to develop a community-based approach to comprehensive reproductive care by undertaking participatory research, fostering mass education with the people's involvement, and by making care available through village-based female workers and improved referral services. We end with two appeals: "MCH" needs to be replaced by WCH: not merely Maternal and Child Health but Woman and Child Health. Care should be provided through a community-based participatory approach, not through narrow technocratic vertical programs. Let people shape their own lives! PMID- 2590476 TI - Commentary on pain management during abortion from a Latin American physician's perspective. PMID- 2590477 TI - Commentary on the causes and consequences of unwanted pregnancy from an African perspective. PMID- 2590478 TI - Abortion counseling: attention to the whole woman. AB - Women's experience of pregnancy and abortion are examined and redefined. Abortion may be undertaken for a variety of reasons, and involves not only physical and emotional health, but also a woman's basic identity. Under restrictive norms and laws set by men, women's decision to abort is a subversive act. Recommendations are made for comprehensive services, including psychosocial counseling to help women cope with social pressures and experience abortion as an act of self affirmation. PMID- 2590479 TI - Commentary on unwanted pregnancy and abortion complications in Cameroun. PMID- 2590480 TI - Liberty, utility, and justice: an ethical approach to unwanted pregnancy. AB - Three moral principles provide an ethical basis for the management of unwanted pregnancy. The principle of liberty guarantees a right to freedom of action; the utilitarian principle defines moral rightness by the greatest good for the greatest number; and justice requires that everyone have equitable access to necessary goods and services. Applied to unwanted pregnancy, these principles yield the conclusion that women have a natural right to reproductive freedom, and a social right to family planning and abortion services. PMID- 2590481 TI - Commentary on unwanted pregnancy, induced abortion, and professional ethics: a concerned physician's point of view. PMID- 2590482 TI - Commentary on the ethics of induced abortion from a feminist perspective. PMID- 2590483 TI - Commentary on the law and abortion in the Philippines. PMID- 2590484 TI - Causes and consequences of unwanted pregnancy from Asian women's perspectives. AB - Shortcomings of contraceptives and of family planning delivery systems are major reasons for unwanted pregnancy and unsafe abortion in Third World countries. Family planning and health programs should provide empathetic counseling for contraceptive choices and pregnancy termination, adjust management systems and procedures to facilitate women's access to services and information, and offer comprehensive services to meet their multiple reproductive health needs. PMID- 2590485 TI - Commentary on abortion law and practice in Cuba. PMID- 2590486 TI - Unwanted pregnancy: challenges for health policy. AB - In Latin America, governments fail to recognize that information and services for sexuality, reproduction and contraception are essential to women's health. Governments should adopt comprehensive women's health policies and programs to help women avoid unwanted pregnancies that lead to dangerous illegal abortions. This includes sex education, especially for adolescents; contraceptive choices; accessible services; decriminalization of abortion and removal of obstacles to legal abortion services; and support for women who wish to carry their pregnancies to term. PMID- 2590488 TI - New challenges for occupational health services facing economic reform in China. AB - In China, which is facing economic reform and the rapid development of small scale industries, various occupational hazards are reappearing. The problems are related to the ignorance of the managers and the workers, a lack of capital, the insufficiency of occupational health services, and the transfer of some hazardous work from large factories in the cities to small plants in the towns and villages. The change in life-style, especially in smoking habits, has aggravated occupational hazards. The problems may be solved by renewing the concept of health among the managers and workers, enforcing legislation related to occupational hazards, strengthening health personnel training, and reinforcing health education and self-help. PMID- 2590487 TI - Safety evaluation of irradiated foods in China: a condensed report. AB - Eight trials, with 439 human volunteers who consumed irradiated foods including rice, potatoes, mushrooms, peanuts, and Chinese sausages, as well as diets composed of multiple irradiated foods (irradiated at dosages of 0.2 to 8 kGy) that accounted for 60-66% of the entire diet, were carried out for 2-3 months according to a unified protocol. No adverse effects on body weight, blood pressure, ECG, hematology, blood enzyme activities, serum lipids or blood or urine 17-hydroxycortisol contents and no chromosomal aberration of peripheral blood lymphocytes were found. It is especially worthwhile to note that there was no change in the polyploidy after consumption of irradiated diets. On the basis of these results and a comprehensive analysis of the physical and chemical characteristics of irradiated foods, temporary hygienic standards for irradiated rice, potatoes, onions, garlic, Chinese sausages, peanuts, and mushrooms were promulgated by the Chinese Ministry of Public Health. PMID- 2590489 TI - Influence of legislation in toxicology. AB - The influence of toxicology on legislation is quite clear in countries where chemicals are regulated by the authorities. There is normally a toxicological evaluation--in addition to other considerations--behind sales and use permissions and the levels that are accepted in food, air, water, etc. How does legislation affect toxicology? If there is no legislation, then clinical and forensic toxicology will be the most used toxicological disciplines (accidents and other cases of poisoning). The more sophisticated and restrictive the legislation becomes, the more toxicology is used not only to permit the use of chemicals but also to ban them. In addition, legislation for the protection of experimental animals has a profound influence in toxicology and accelerates the use of in vitro and other alternative methods. This paper discusses whether countries in the "developed" world are overdoing it, thereby maybe hampering the essential use of chemicals in the developing countries. PMID- 2590490 TI - Hexachlorobenzene episode in Turkey. AB - During the period 1955-1959, approximately 4000 people in southeast Anatolia developed porphyria due to the ingestion of hexachlorobenzene (HCB), a fungicide added to wheat seedlings. These HCB exposures subsequently led to the development of bullae on sun-exposed areas, hyperpigmentation, hypertrichosis, and porphyrinuria. The condition was called kara yara or "black sore." Many of the breast-fed children under the age of 2 years whose mothers had ingested HCB treated grain died from a disease known as pembe yara or "pink sore." In this follow-up study of 252 patients, 20-30 years postexposure, there were 162 males and 90 females, with an average current age of 35.7 years, an average of onset of 7.6 years, and a duration of 2.2 years. Many patients had dermatologic, neurologic, and orthopedic symptoms and signs. The observed clinical findings include scarring of the face and hands (83.7%), hyperpigmentation (65%), hypertrichosis (44.8%), pinched facies (40.1%), painless arthritis (70.2%), small hands (66.6%), sensory shading (60.6%), myotonia (37.9%), cogwheeling (41.9%), enlarged thyroid (34.9%), and enlarged liver (4.8%). Urine and stool porphyrin levels were determined in all patients, and 17 have at least one of the porphyrins elevated. A total of 56 specimens of human milk obtained from mothers with porphyria were analyzed for HCB. The average value was 0.51 ppm in HCB exposed patients compared to 0.07 ppm in unexposed controls. Offspring of mothers with three decades of HCB-induced porphyria appear normal. PMID- 2590491 TI - Quality assurance in toxicology studies in developing countries. AB - As developing countries become more involved in the international chemical trade, they must adhere to certain requirements for importation of their chemicals into foreign countries. These developing countries will be required to provide basic safety information on their chemical products, including data developed from chemical and toxicologic testing. These data must be developed in accordance with the national requirements of the importing country. Many importing countries have adopted the OECD Test Guidelines and the OECD Principles of Good Laboratory Practice (GLP) as primary guidance to assure the quality of laboratory data. These procedures provide a basis for internationally acceptable data. Several countries have incorporated many of these provisions into their national laws or administrative procedures. These procedures describe the process of documenting the conduct of laboratory studies, including recording of data, reporting of study results, and storage of data gathered. This process is intended to assure the quality and integrity of the data so that, if required, the study can be reconstructed by an auditor or an inspector. Details of these procedures and their applicability to the international chemical trade are discussed. PMID- 2590492 TI - The risk of risk assessment. AB - Appropriate risk management can only be based on sound risk assessment. The sources of uncertainty involved in risk assessment are discussed and a number of approaches to improving such assessments are recommended. PMID- 2590493 TI - Effects of adrenalectomy and corticosterone on hippocampal lesions induced by trimethyltin. AB - The effects of adrenalectomy and corticosterone supplementation on the neurotoxicity of trimethyltin (TMT) were tested. CD-1 mice with or without adrenalectomy were injected with TMT at a dose of 3.0 mg/kg body wt. At 48 h post TMT administration, the animals were killed for pathological examination. It was found that the adrenalectomized animals developed even more severe lesions in the hippocampal formation (fascia dentata granule cells) than the intact animals. When animals were given a supplement of corticosterone pellets at doses of 0.15, 1.5, and 7.5 mg, there was a reduction of lesion development. Total alleviation of pathology was seen at the two higher doses of supplementation. Our present investigation strongly indicates that there may be a close and important interrelationship between TMT-induced neurotoxicity and adrenal function. PMID- 2590494 TI - Fermented corn flour poisoning in rural areas of China. III. Isolation and identification of main toxin produced by causal microorganisms. AB - Flavotoxin A was isolated from Pseudomonas cocovenenans subsp. farinofermentans culture in semisolid potato-dextrose-agar medium, which was isolated from fermented corn meal that had caused food poisoning outbreaks in China. The isolation, purification, and chemical structure of this toxin were studied. The NMR spectra, the uv spectra, and molar extinction coefficients, and the mass spectra of Flavotoxin A are in good agreement with those reported for bongkrekic acid. Therefore, Flavotoxin A and bongkrekic acid are the same organic chemical compound; the molecular formula is C28H38O7. The oral LD50 of the purified Flavotoxin A in mice was 3.16 mg/kg (1.53-6.15 mg/kg). The existence of bongkrekic acid in toxic fermented corn samples collected during food poisoning outbreaks was also confirmed. It is concluded that bongkrekic acid has played an important role in the outbreaks of fermented corn poisoning. PMID- 2590495 TI - Importance of the development of veterinary toxicology in Argentina. AB - The different types of toxic substances that affect farm animals in Argentina are described. These substances include (a) toxic plants, such as Solanum glaucophyllum, Baccharis coridifolia, Festuca arundinacea; (b) mycotoxins, such as zearalenone, tremorgenic mycotoxins, and ergoalkaloid; (c) trace elements, such as fluorine, copper, molybdenum, and arsenic; and (d) others, such as toxic algae and pesticides. The direct and indirect economic loss of farm animals associated with these toxic substances in Argentina is roughly estimated at 50 million dollars a year. A number of recommendations are made to ameliorate the situation. PMID- 2590496 TI - Realistic assessment of health hazards of chemicals. PMID- 2590497 TI - Toxic effects of pirimiphos-methyl residues on rats. AB - This study analyzes the level of total and bound pirimiphos-methyl residues in treated wheat grain and its toxic effects on rats. Wheat grain was treated with [14C]pirimiphos-methyl of 16.36 mCi/mmol specific activity to determine the bioavailability of bound residues in rats. At the same time, grain was treated with nonlabeled pirimiphos-methyl as required to determine any possible toxic effects of bound residues in a subacute feeding study in rats. Two dose levels were used: 10 and 100 ppm (the former being the recommended dose level in practical treatment). Estimation of the type of residues was performed at intervals of 0, 30, 90, 120, 150, and 180 days. During and after the animal feeding study, changes in body weight gain, organ weight, cholinesterase activity, serum enzyme activity, and hematology were investigated. There is an indication that bound residues of the pesticide pirimiphos-methyl provoke toxic effects to some extent. PMID- 2590498 TI - Lead concentration in Hong Kong roadside dust after reduction of lead level in petrol. AB - Samples of roadside dust were collected from 30 sites in Hong Kong. The total concentrations of 10 metals in the samples were analyzed, and the correlation coefficients among the metal contents and the annual average daily traffic (AADT) in 1986 were determined. Pb was found to have a significant correlation (P less than 0.01) with AADT. No correlation was found between Al, Ba, Cd, Cr, Cu, Fe, Mn, Ni, and Zn with respect to AADT. A general decrease in the level of Pb in roadside dust in the past few years has been observed since the reduction in the level of lead in petrol. PMID- 2590500 TI - Short-term test for the induction of lung tumor in mouse by chloroprene. AB - In a previous study by the authors, positive results from both a case-control study and a cohort study were reported. In the present study a short-term test for the induction of mouse lung tumor by chloroprene was conducted to confirm whether chloroprene monomer itself can induce tumors. Kunming albino mice weaned at 2 weeks were subjected to inhaling 0, 2.9 +/- 0.3, 19.2 +/- 1.9, and 189.0 +/- 13.3 mg/m3 chloroprene (GC purity, 99.8%) 4 h daily (except Sunday) for 7 months. All survivors were killed at the end of the 8th month or when moribund. No lung tumors were found before the 6th month. Thus, survivors at the 6th month were counted as effective animals. Most lung tumors observed were papilloadenomas (50/57), and a few were adenomas (7/57). The tumor incidence in the 2.9 mg/m3 group was 8.1% in comparison to 1.3% in the control group, with the significance level at P less than 0.05. The higher the concentration, the higher the incidence. Examination of the multiplicity of tumor induction also demonstrated a dose-response relationship, and the number of tumors per mouse in the 189 mg/m3 group was significant at P less than 0.01. PMID- 2590499 TI - Epidemiologic study of cancer mortality among chloroprene workers. AB - Both case-control and cohort studies were undertaken from July 1, 1969 to June 30, 1983 to ascertain whether exposure to chloroprene increases the risk of cancer. Fifty-five cases of cancer deaths were verified, 16 of which had histories of exposure to chloroprene ranging from 3 to 23 years (median 11 years) with a latent period of 8-27 years, except for one case of 3 years (median 12.5 years). Fifty-four pairs were obtained by matching the cancer deaths to noncancer deaths in accordance with strict requirements. The odds ratio for the paired data was 13, X2 = 8.64, P less than 0.005. The average age at death from cancer of workers exposed to chloroprene was 12.7 years younger than that of unexposed workers, t' = 2.98, P less than 0.001. The total cohort consisted of 1213 persons, among whom 149 (11.6%) had histories of exposure for over 25 years, 381 (31.5%) for over 20 years, and 852 (70.2%) for over 15 years. The SMR for the total cohort was 2.38 (P less than 0.01), and all SMRs for the high-exposure occupations were of significance (P less than 0.05 or P less than 0.01), in contrast to those of the low-exposure grups whose SMRs were low or zero. Thus, a dose-response relationship existed. Among the high-exposure occupations, maintenance mechanics seem to have the highest risk of cancers, and SMRs for liver, lung, and lymphatic cancers were significant in this group. These results suggested that chloroprene exposure increases the risk of developing cancer. PMID- 2590501 TI - Carcinogenesis by nitrosamines and azoxyalkanes by different routes of administration to rats. AB - The effects of administering similar doses of some simple alkylating agents to rats by different regimens have been compared. Two of the compounds were methylating agents, nitrosodimethylamine and azoxymethane; two were ethylating agents, nitrosodiethylamine and azoxyethane; and nitrosomethylethylamine was both a methylating and an ethylating agent. The treatments gave rise to tumors in almost all treated rats. The results indicate the importance of pharmacokinetics in determining which organs are the targets of the alkylating carcinogens. PMID- 2590502 TI - The uniform carcinogenic action of alkylnitrosoureas in Syrian hamsters. AB - The carcinogenic effects of a number of alkylnitrosoureas in Syrian golden hamsters have been compared by administering them by gavage as solutions in corn oil/ethyl acetate. The compounds were methyl-, ethyl-, 2-hydroxyethyl-, 2 oxopropyl-, and 2-phenylethylnitrosourea and the dialkylnitrosoureas dimethyl- and diethylnitrosourea, ethylnitrosohydroxyethylurea, ethylnitroso-2 oxopropylurea, 2-oxopropylnitrosochloroethylurea, and hydroxyethylnitrosoethylurea. All were given at approximately equimolar doses and, in most cases, to male and female hamsters. Most of the hamsters died with tumors associated with the treatments. Methylnitrosourea, ethylnitrosourea, and hydroxyethylnitrosourea, but not oxopropylnitrosourea, gave rise to a high incidence of tumors of the forestomach, while the dialkylnitrosoureas produced smaller numbers of forestomach tumors. All of the alkylnitrosoureas induced hemangiosarcomas of the spleen, which was the most common tumor produced by these carcinogens. Tumors of other types were uncommon, except that ethylnitrosourea and ethylnitrosohydroxyethylurea induced tumors of the cervix in about half of the animals and ethylnitrosooxopropylurea induced some nervous system tumors. The small number of common target organs of alkylnitrosoureas in hamsters contrasted sharply with the broad spectrum of tumors they induced in rats, depending on the nature of the alkyl groups, and with a quite different order of potency in the latter species. PMID- 2590503 TI - Morphological changes in the gills of tilapia fed sterilized and nonsterilized sludge. AB - The effects of digested sludge on the ultrastructure of gills of Sarotherodon mossambicus were investigated. Samples of digested sludge were collected from the Shatin Sewage Treatment Plant in Hong Kong and they were (1) sun-dried (NS) or (2) sterilized in an autoclave (SS). They were then used as supplementary fish feed to cultivate the freshwater tilapia, S. mossambicus, for 50 days under laboratory conditions. The SS at low dosage (25%) had the lowest toxicity among different treatments. A swelling of lamellar epithelium, the enlargement of the the subepithelial space, the collapse of capillaries, and the infiltration of polymorphonuclear cells in the lamellae of fish gills were common to fish fed 50 to 100% NS and SS. The thickening of the basal lamina in the gill lamellae is a common feature found in the sludge-treated fish. PMID- 2590504 TI - Smelting, underground mining, smoking, and lung cancer: a case-control study in a tin mine area. AB - An increased risk of lung cancer in the Dachang tin mine of Guangxi has been reported. To investigate the factors contributing to the excessive risk of lung cancer, we conducted a matched case-control study in the mine area and analyzed the effects of multiple factors, such as living and housing conditions, occupational exposure, and smoking, with the methods of conditional logistic regression. The case series consisted of 69 patients with primary bronchial cancer, 55 of whom had died. The control series consisted of 138 individuals, 55 of whom were decreased. The results showed that the factors contributing to the excessive risk of lung cancer in the mine area related mainly to occupational exposure. The significant risk factors were time of exposure to smelting, time of exposure to underground mining, and age at which underground mining was begun. In study model II where living controls were used, daily consumption of cigarettes was an additional risk factor. Furthermore, there was a synergistic action among these factors. The relation of the risk factors to lung cancer is discussed. PMID- 2590505 TI - Nuclear Overhauser effect and computational characterization of the beta-spiral of the polypentapeptide of elastin. AB - The structure of the elastin polypentapeptide, poly(VPGVG), was studied by nuclear Overhauser effect experiments using perdeuterated Val1 and Val4 samples under the condition where intermolecular interactions are absent. More extensive interaction was found between the Val1 gamma CH and Pro2 beta CH protons than between the Val4 gamma CH and Pro2 beta CH protons. The Val1 gamma CH3-Pro2 beta CH interaction does not occur within the same pentamer as previously shown experimentally and as expected from steric considerations. The results are incompatible with the presence of a random chain network in poly(VPGVG) at room temperature but are readily explicable in terms of interturn interactions in a beta-spiral structure. More specifically, the results indicate that the beta spiral conformation with 2.9 pentamers/turn is more prevalent than that with 2.7 pentamers/turn. Using conformations developed by molecular mechanics calculations, molecular dynamics simulations were carried out to compare the relative energies of these two variants of this class of beta-spiral structures. It was found in vacuo that the structure with 2.9 pentamers/turn is indeed more stable than that of 2.7 pentamers/turn by approximately 1 kcal/mole-pentamer. PMID- 2590506 TI - An estimate of the extent of folding of nucleosomal DNA by laterally asymmetric neutralization of phosphate groups. AB - We attempt quantitative implementation of a previous suggestion that asymmetric charge neutralization of DNA phosphate groups may provide part of the driving force for nucleosome folding. Polyelectrolyte theory can be used to estimate the effective compressive force acting along the length of one side of the DNA surface when a fraction of the phosphate groups are neutralized by histones bound to that side. A standard engineering formula then relates the force to the bending amplitude caused by it. Calculated bending amplitudes are consistent with the curvature of nucleosomal DNA and the overall extent of charge neutralization by the histones. The relation of the model to various aspects of nucleosome folding, including the detailed path of core-particle DNA, is discussed. Several other DNA-protein complexes are listed as examples of possible asymmetric charge induced bending. PMID- 2590507 TI - Electron microscopy of supercoiled pEJ4 DNA containing homopurine.homopyrimidine sequences. AB - Supercoiled pEJ4 DNA (a derivative of pUC19 containing an insert with 60-bp-long homopurine.homopyrimidine tract from the sea urchin P. miliaris histone gene spacer) was investigated by electron microscopy using three different spreading techniques i.e., formamide and aqueous variants of the Kleinschmidt technique and protein-free benzyldimethyl-alkyl ammonium chloride (BAC) technique at different pHs. If the specimens for electron microscopy were prepared at pH 5.6 and pH 4.0 (i.e., under conditions where the homopurine.homopyrimidine tract assumes an unusual conformation) a single thick "stem" or a "denaturation bubble" in a large number of DNA molecules were observed. No such changes were found in samples prepared at neutral pH and in linearized pEJ4 DNA prepared at pH 5.6. In specimens of a control supercoiled pUC19 DNA prepared at pH 5.6 and 4.0 practically no local changes were detected. The "denaturation bubbles" were observed by BAC techniques (probably due to secondary local DNA denaturation during the specimen preparation) while the more gentle formamide technique revealed only "stems". The "stems" were almost always positioned at the sites where the curvature of supercoiled DNA molecules occurred. The results are in agreement with presence of a protonated triplex H-form in homopurine.homopyrimidine tract bringing the first evidence of curvature or kinking of the DNA molecule connected with the occurrence of the H-form in supercoiled DNA. PMID- 2590508 TI - Structural alteration from non-B to B-form could reflect DNase I hypersensitivity. AB - Preferential cleavage of active genes by DNase I has been correlated with a structurally altered conformation of DNA at the hypersensitive site in chromatin. To have a better understanding of the structural requirements for gene activation as probed by DNase I action, digestability by DNase I of synthetic polynucleotides having the ability to adopt B and non-B conformation (like Z form) was studied which indicated a marked higher digestability of the B-form of DNA. Left handed Z form present within a natural sequence in supercoiled plasmid also showed marked resistance towards DNase I digestion. We show that alternating purine-pyrimidine sequences adopting Z-conformation exhibit DNAse I foot printing even in a protein free system. The logical deductions from the results indicate that 1) altered structure like Z-DNA is not a favourable substrate for DNase I, 2) both the ends of the alternating purine-pyrimidine insert showed hypersensitivity, 3) B-form with a minor groove of 12-13 A is a more favourable substrate for DNase I than an altered structure, 4) any structure of DNA deviating largely from B form with a capacity to flip over to the B-form are potential targets for the DNase I enzymic probes in naked DNA. PMID- 2590509 TI - The concentration dependence of the right to left conformational transition in natural DNA identified by Raman spectroscopy. AB - The classical and resonance Raman spectra of DNA from Chicken Erythrocytes have been obtained for different DNA concentrations in solution with low and high ionic strengths. The classical Raman spectra of 30 mg/ml DNA solutions were measured in varying the sodium chloride concentration from 0.1 to 4.5 M NaCl. An increase in the salt content of the solution leads to spectral changes in the 600 700 cm-1 region, indicating a C2' endo/anti to C3' endo/syn conformational transition of the purine residues. Other changes around 840 cm-1, due to the antisymmetrical stretching vibration of the PO2 group, are also detected: they were characteristic for the B----Z transition in model systems such as poly(dG dC).poly(dG-dC). The resonance Raman spectra of low (1 mg/ml) and high (30 mg/ml) concentrated DNA solutions were obtained with low (0.1 M) and high (4.5 M) NaCl contents, in using a 284 nm excitation wavelength. No change was observed in the intensities and band positions in the low and high salt solutions of low concentrated DNA. Thus it is assumed that the DNA structure remains unchanged whatever the salt concentration for low concentrated DNA. In contrast, great modifications of the intensities and positions of some lines were found in the spectra of high DNA concentration solution when the NaCl content is increased up to 4.5 M: these changes resemble to some extent those observed in the study of B- --Z transition of several polynucleotide model compounds. It is assumed that the right-handed to left-handed conformational transition may occur in certain sections of natural DNA, likely containing alternating purine-pyrimidine sequences, when the DNA concentration is sufficiently important. PMID- 2590510 TI - A combined 2D-NMR and molecular dynamics analysis of the structure of the actinomycin D: d(ATGCAT)2 complex. AB - We present a comparative analysis of an NMR experiment and molecular and harmonic dynamics simulations of an actinomycin D: d(ATGCAT)2 complex. A comparison of NOE measurements and 1/R6 weighted proton-proton distances confirm the general correctness of the Actinomycin D-DNA model proposed by Sobell. There are, however, some substantial differences between the proton-proton distances inferred from the NOE results and the molecular and harmonic dynamics simulations. The remaining discrepancies could either come from contributions of other conformations to the average properties of the complex or from uncertainties in the NMR distance analysis. An analysis of the molecular dynamics helix properties, sugar puckers, hydrogen bonding, rms fluctuations and torsional properties are qualitatively consistent with those from previous simulations, but the presence of an intercalated drug leads to some new structural and dynamical features. PMID- 2590511 TI - Conserved signals around the 5' splice sites in eukaryotic nuclear precursor mRNAs: G-runs are frequent in the introns and C in the exons near both 5' and 3' splice sites. AB - It is known that the GT doublet is well conserved at the 5' exon/intron splice junction and is frequently embedded in the AGGT quartet. Although only the underlined G is invariable, splicing and ligation are accurately executed. In this work we search for additional conserved potential signals which may aid in 5' splice site recognition. Extensive searches which are not limited to a preconceived consensus sequence are carried out. We investigate the distributions of the 256 quartets in a 1000 nucleotide span around the 5' splice sites in approximately 1700 eukaryotic nuclear precursor mRNAs. Several potential signals are noted. Of particular interest are quartets containing runs of G, e.g., G4, G3T, G3C, G3A and AG3 in the intron immediately downstream and some C-containing quartets in the exon upstream of the 5' splice site. In an analogous calculation, (A)GGG(A) has also been found to be frequent in the intron, 60 nucleotides upstream and (A)CCC(A) in the exon downstream of the 3' splice site. These results are consistent with the recent indications that exon sequences may play a role in efficient splicing. Some models are proposed. PMID- 2590512 TI - Correlates of drug therapy of diastolic blood pressure between 80-89 mm Hg by physicians in the community. AB - We have conducted a random probability survey of primary care physicians (n = 477) to examine the factors which might influence the level of diastolic blood pressure (DBP) felt by physicians to warrant antihypertensive drug therapy in young adults. Of the responding physicians, 18.4% reported treating young adults who had a DBP of less than 90 mm Hg. This practice was correlated with physician opinions about the efficacy of hypertension treatment and the reported influence of pharmaceutical representatives on physician practice. We conclude that reported therapy of DBP less than 90 mm Hg in young adults is highly prevalent. Such therapy is correlated with physician opinions as well as the perceived influence of pharmaceutical sources of information. PMID- 2590513 TI - Beats modulate blood pressure during running. AB - Blood pressure (BP) changes during running were studied in 25 subjects with intraarterial monitoring. Periodic pulse pressure variations ranging from 20 to 200 mm Hg were recorded throughout the exercise. To prove that these pressure oscillations were due to a "beat" phenomenon 10 athletes ran with a Teruflex container filled with saline: pressure changes up to +/- 62 mm Hg were recorded in the container. These pressure waves were added by computer to the sphygmic waves recorded intraarterially in the same subject during bicycle ergometry: the resultant tracing showed a beat-shaped pattern similar to that recorded during running. PMID- 2590514 TI - . . . Being alive is a fatal disease . . . PMID- 2590515 TI - Methodological considerations contributing to variability of the quadriceps H reflex. AB - The clinical usefulness of the quadriceps H-reflex is limited because of the difficulty of elicitation and its inherent variability in amplitude. In the present study we attempted to identify the influence of methodological variables (head position and remote muscle contractions) on the amplitude of the H-reflex evoked in vastus medialis, vastus lateralis and rectus femoris from the right leg of 13 healthy adult subjects. Square wave stimuli (1-ms duration) were delivered percutaneously to the femoral nerve. The 50% maximal amplitude H-reflexes were evoked while the subject reclined with head facing to the right, left, up and down or while the subject performed Jendrassik's maneuver. The results show a significant increase in the reflex amplitude when the subject's head was turned to the right; there was either a mild increase or no change in amplitude of the response when the subjects faced to the left, up and down. The evoked potential tended to decrease when the subjects closed their eyes; however, the tendency to increase with neck position was not changed. Remote muscle contractions enhanced the amplitude of the response. These results present further evidence of the characteristics of the quadriceps H-reflex and identify postural influences as one controllable source of variability in the L3-L4 root electrodiagnostic test. PMID- 2590517 TI - The demeaning of rehabilitation. PMID- 2590516 TI - Research in physical medicine and rehabilitation. VI. Research project management. AB - This article on research project management is written primarily for the researcher who has started a project, has collected data on a few subjects and has now realized that the project is more involved than anticipated. Although discussion of the many different styles of management is beyond the scope of this article, it addresses some common problems faced by the researcher, including finding subjects, obtaining project approval from the institutional review board, identifying and training staff, establishing a work plan, pilot testing, recording data, identifying problems, using computer software for project management and budgeting. Specific examples and exercises are included. PMID- 2590518 TI - Relationship of muscle strength of back and upper extremity with level of physical activity in healthy women. PMID- 2590519 TI - [Diurnal differences in alcohol absorption]. AB - Under standardized conditions five subjects were submitted twice to a dose of alcohol of 1.1 g/kg. This dose was administered once between 7:15 and 7:45 am. and at a different day between 7:15 and 7:45 pm. The blood alcohol concentration curves in the morning and the evening differed significantly in peak and time elapsed until this value was reached. During the morning the peak averaged 32% higher than in the evening. In the morning it was reached after about 60 min and during evening after 110 min. The elimination rate was about the same. These results show that alcohol is significantly faster absorbed into the blood in the morning than during the evening. This could be explained by accelerated transport of uptaken alcohol into the bowels. PMID- 2590521 TI - [A behavioral scientific model of the drunk driver]. AB - With the introduction of modifying programs (driver improvement) the ability to drive can no longer be taken as an invariant character trait, but as a competence that can be mediated by courses. The consequences of this development are shown in the case of drinking driving offender. Typical actional settings, which have proved their importance in the diagnostic and especially in the rehabilitative work of the author, are discussed. Case histories show how persons deal with these settings. The chosen conceptual representation seems to be appropriate to communicate with the afflicted person. It provides identification patterns that facilitate the organization and verbalization of experiences. Reflection of the actional setting and the coping behavior starts a process that aims at the normalization of existencial references. It appears, that the most dangerous effect of the misuse of alcohol is to make actual conditions permanent. The hindrance of development and change becomes the real problem. For the expert this approach offers a heuristic, which helps to discern omissions, shortenings and contradictions in the utterances of the subject and, above all, can point out ways, which lead out of the problematic situation. PMID- 2590520 TI - [Use of breath alcohol analysis in France]. AB - An alcohol legislation concerning the operation of motor vehicles exists in France since 1954. In the meantime the problem of the great number of accidents caused by drivers under the influence of alcohol has required several modifications of the legal regulations. In order to get an effective prevention of alcohol-induced traffic accidents the present and future strategy of the French authorities is mainly based on an intensified application of preliminary and evidential breath-alcohol analysis. The legal limit for breath alcohol was fixed at 0.4 mg/l without a direct reference to the blood alcohol limit. PMID- 2590522 TI - [New methods for pharmacokinetic assessment of alcohol and its metabolites in male and female probands]. AB - The pharmacokinetics of ethanol and its metabolites were examined in 10 young healthy women and men after 1-hr intravenous ethanol application of 7.8 mmol/kg body weight. Therefore, a new pharmacokinetic model takes into account Michaelis Menten-elimination kinetics of ethanol as well as kinetics of acetaldehyde and acetate, which are defined by first order processes. The metabolite-model adequately describes the ethanol and acetate concentration courses. In fact, the observed ethanol concentrations are so close to the model-predicted values, that the metabolite-model allows an evaluation of half-life-times of acetaldehyde and acetate. The analyses of ethanol infusion studies showed, that there are no sex differences in parameters of ethanol elimination: Maximal elimination velocity Vmax was 3.41 +/- 0.61 mmol/l.h in females and 3.98 +/- 0.69 mmol/l.h in males. Michaelis-Menten-constant kM was 1.49 +/- 0.44 mmol/l and 1.69 +/- 0.88 mmol/l, respectively. In the female group, the volume of distribution of ethanol V1 was with 38.4 +/- 5.0 l significant smaller than in males with 50.5 +/- 3.5 l. In conclusion, the new metabolite-model can be used as a basis for the investigation of the entire alcohol metabolism. PMID- 2590523 TI - [King Solomon was wise after all. Defensive comment for saving the reputation of a deceased person and summons for the education of descendents]. AB - Referring to the Bible the author contradicts Stephan's statement (Blutalkohol 26, 249) that Solomon was not "wise". He maintains and explains in detail that nowadays jurists and psychologists cannot be "wise" in a biblical sense. He welcomes and, considering it more deeply, supports the demand that with investigations through experts and with the corresponding valuation through jurists prejudices are to be avoided and that defendants and probationers are to be fully informed. PMID- 2590524 TI - Purification and partial amino acid sequence of a glutamyl-tRNA synthetase from Rhizobium meliloti. AB - A glutamyl-tRNA synthetase has been purified to homogeneity from Rhizobium meliloti, using reversed-phase chromatography as the last step. Amino acid sequencing of the amino-terminal region of the enzyme indicates that it contains a single polypeptide, whose molecular weight is about 54,000, as judged by SDS gel electrophoresis. The primary structures of the amino-terminus region and of an internal peptide obtained by cleavage of the enzyme with CNBr have similarities of 58 and 48% with regions of the glutamyl-tRNA synthase of Escherichia coli; these are thought to be involved in the binding of ATP and tRNA, respectively. The small amount of glutamyl-tRNA synthetase present in R. meliloti is consistent with the metabolic regulation of the biosynthesis of many aminoacyl-tRNA synthetases. PMID- 2590525 TI - Factors influencing the heat shock response of Xenopus laevis embryos. AB - We have further characterized the heat shock response of Xenopus laevis embryos. Xenopus embryos respond to heat shock by consistently synthesizing four major heat shock proteins (hsps) of 62, 70, 76, and 87 kilodaltons. In addition to these hsps, heat-shocked embryos also exhibit the synthesis of several minor hsps. The synthesis of these hsps is often variable. We have monitored the effects of different temperatures and lengths of heat shock on the pattern and intensity of hsp synthesis. In general, the four major hsps are induced more strongly at higher temperatures and during increasing intervals of heat shock. The temperature and duration of heat shock can affect the synthesis of the minor hsps, however. Some hsps are synthesized at lower temperatures only (i.e., below 37 degrees C), whereas others are synthesized only at higher temperatures (i.e., above 37 degrees C). We have extensively examined the characteristics of hsp 35 synthesis, one of the most variably synthesized hsps. This hsp is characteristically synthesized at temperatures above 35 degrees C and usually during the first 40 min of heat shock, after which it becomes undetectable. In some experiments, its synthesis is restimulated during later intervals of heat shock. Hsp 35 is also under developmental regulation. It is not synthesized by heat-shocked embryos until the late blastula to early gastrula stage. After this brief period of inducibility, its synthesis is dramatically reduced in mid- to late gastrulae, but reappears in heat-shocked neurulae. We have previously demonstrated that hsp 35 is related to the glycolytic enzyme glyceraldehyde-3 phosphate dehydrogenase (GAPDH). The induction of hsp 35 synthesis is inversely correlated with the constitutive levels of GAPDH specific activity. In this paper we document further correlations between the synthesis of hsp 35 and GAPDH specific activity during early Xenopus development. PMID- 2590526 TI - Lipoprotein-mediated efflux of radiolabeled cholesterol from cells does not indicate net removal of cellular cholesterol mass. AB - The efflux of cholesterol from human skin fibroblasts was determined using radioisotope techniques and mass measurements. When the cells were labeled with [14C]- or [3H]-cholesterol and then incubated with very low density, low density, or high density lipoproteins or with serum, 20 to 30% of the label was released into the medium in 20 h. However, when the cellular cholesterol content was determined after incubation with various lipoproteins under identical conditions, only the heavier subfraction of high density lipoproteins (HDL3) caused a significant decrease in cellular cholesterol. This net removal of cholesterol can be observed in the cells without overloading them with cholesterol, by incubation with low density lipoproteins. Time studies indicated that at least 24 h of incubation is required to detect significant removal of cellular cholesterol. These experiments show that methods using the release of labeled cholesterol from cultured cells to determine net cholesterol removal mediated by high density lipoprotein, although currently used by many investigators, can lead to erroneous conclusions when employed without the measurement of cholesterol mass. PMID- 2590527 TI - Proteolytic degradation of HDL1 on the fat cell surface is nutritionally regulated. AB - The importance of plasma HDL apolipoprotein concentration as a predictor of atherosclerotic risk is well recognized, yet the processes of HDL modification and degradation in various cells are not clearly understood. We examined the characteristics of HDL1 apolipoprotein degradation and cellular uptake by rat adipocytes and determined the effects of fasting on these processes. Epididymal and perirenal adipocytes were isolated from male Wistar rats (310 +/- 4 g) fed ad libidum and incubated with 5 micrograms of rat 125I-labeled HDL1 (d: 1.07-1.10 g/mL) mL-1 for 2 h at 37 degrees C. Cellular uptake of HDL1 was calculated as the trichloroacetic acid precipitable radioactivity associated with adipocytes following incubation. Intracellular and medium degradation of HDL1 were determined as trichloroacetic acid soluble 125I counts associated with cells and measured in the postincubation medium, respectively. Fifty to sixty percent of cellular uptake and degradation of HDL1 was inhibited by the addition of 25-fold excess unlabeled HDL. HDL1 degradation measured in the medium was 10- to 12-fold greater than cellular uptake of HDL1 apolipoproteins. Intracellular degradation of HDL1 was negligible. The presence of EDTA in the incubation medium reduced HDL1 degradation measured in the medium, but enhanced HDL1 cellular uptake. Conditioned medium separated from cells after 2 h of incubation at 37 degrees C in the absence of HDL and subsequently incubated with 125I-labeled HDL1 for an additional 2 h at 37 degrees C, degraded less than 5% of HDL compared with degradation in the presence of cells. These results suggest that rat adipocytes degrade, or modify, HDL1 particles, possibly by interactions with cell surface proteases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590528 TI - Studies on the ATP requirements of in vitro chromatin assembly. AB - To gain a more complete understanding of the process of in vitro chromatin assembly, an examination of the energy requirements of nucleosome formation must be undertaken. The experiments outlined in this manuscript address this issue by making use of the Xenopus laevis S-150 cell-free extract. The S-150 catalyzes chromatin assembly on circular DNA templates dependent either on the exogenous addition of ATP or regeneration of endogenous ATP. We define two distinct, but temporally ordered, phases of the overall process. The first, nucleosome formation, occurs in the presence of endogenous levels of ATP, while the second phase, chromatin assembly, which we define as the development of properly spaced nucleosomes, requires a higher level of ATP. Both phases lead to a distribution of molecules with similar superhelical densities. Taken together, these data suggest that chromatin assembly may consist of two distinct steps differing in their strategy cofactor requirement. The experiments presented in this manuscript support the concept that nucleosomes first assemble, perhaps randomly, on the DNA and are gradually matured into a canonical chromatin structure with periodic spacing. PMID- 2590530 TI - Freeze fracturing properties of native and heat-adapted Chinese hamster ovary (CHO) cells. AB - Chinese hamster ovary cells were either maintained at 37 degrees C (native cells) or heat adapted by exposure to a temperature of 40 degrees C for 2 h. Thereafter, native and heat-adapted cells were incubated at different temperatures for various times, harvested, fixed with glutaraldehyde and glycerol, and studied by freeze fracture microscopy. We observed that the fracture plane either passed through the cell, exposing cytoplasm, or stayed within the plasma membrane, and that the location of the fracture plane was strongly determined by the previous thermal history of the cell. We believe that these differences reflect changes in membrane lipid packing arrangements. PMID- 2590529 TI - Acetate assimilation by the fission yeast, Schizosaccharomyces pombe. AB - The fission yeast Schizosaccharomyces pombe utilizes acetate at subinhibitory concentrations in the presence of D-glucose. The nonionized form of acetate is preferentially utilized, oxidized to 14CO2, and assimilated into lipids and proteins. Acetyl CoA synthetase activity greatly increases in the yeast cells grown in media containing acetate. However, glyoxylate cycle enzymes are not detectable in Schizosaccharomyces pombe. [1-14C]Acetate is incorporated into stereols, sterol esters, neutral lipids, and phospholipids. Assimilation of [1 14C]acetate into the peptide structure of proteins was confirmed by a proteolytic digestion experiment. PMID- 2590531 TI - Thioredoxin and glutaredoxin enhance the binding of L-triiodothyronine to its hepatic nuclear receptors. AB - The influence of thioredoxin and glutaredoxin on binding of L-triiodothyronine (T3) to the rat hepatic nuclear T3 receptor was compared with that of the exogenous activator dithiothreitol. Specific [125I]T3 binding, the affinity constant, Ka, and the maximal binding capacity, MBC, were measured using whole nuclei, solubilized preparations of receptor, and chromatographed nuclear receptor. Both the thioredoxin system (thioredoxin, thioredoxin reductase, and NADPH) and the glutaredoxin system (glutaredoxin, glutathione reductase, glutathione, and NADPH) increased specific binding of T3 to nuclei, solubilized receptor, and chromatographed receptor significantly. Compared with the values obtained in the absence of added thiol (Ka = 1.6 +/- 0.1 x 10(9) M-1, MBC = 1.7 +/- 0.06 pM), the thioredoxin and glutaredoxin systems increased Ka by 147 and 112%, respectively, while decreasing MBC by 51 and 45%, respectively, when chromatographed receptor was used. The same tendency was observed with solubilized receptor. However, dithiothreitol increased Ka without affecting MBC when solubilized receptor was used. These results, the first demonstration of endogenous disulphide reductant systems enhancing binding of T3 to its receptor, suggest that the thioredoxin and (or) glutaredoxin systems may modulate the physiological effects of thyroid hormone. PMID- 2590533 TI - Trends in cardiac metastasis. AB - A review of 8571 autopsies disclosed 2833 patients with malignant tumours from 1975 to 1984 at the Department of Pathology, The Gade Institute. Cardiac metastases were found in 130 cases. An increase of cardiac involvement was shown in the autopsy material from 1.2% in 1975-1979 to 1.8% in 1980-1984. The same trend was seen if cardiac metastases were related to malignant tumours. Numerically, lung cancer accounted for most of the metastases seen, but the increase was made up by other tumours than lung cancer. especially malignant melanoma, mesothelioma, breast cancer and sarcomas. These tumours have a high frequency of heart metastases and the increased incidence of these cancers in the material explains the rise of cardiac metastases. Cardiac metastases increased with rising number of distant metastases. This study shows that mesotheliomas have the highest percentage of cardiac spread. The importance of autopsy for detecting metastatic spread in sites that are difficult to detect clinically is emphasized. PMID- 2590532 TI - Ependymoma of the ovary. A clinico-pathologic, ultrastructural and immunohistochemical investigation. A case report. AB - A case of primary malignant ovarian ependymoma is described. The course of the tumor disease was extremely prolonged with a 50 year history. The diagnosis is supported by immunohistochemical and ultrastructural evidence of ependymal differentiation. The histogenesis and the origin from a possible preexisting ovarian teratoma are discussed. PMID- 2590534 TI - B cell associated monoclonal antibody L26 may occasionally label T cell lymphomas. AB - Monoclonal antibody L26 has been shown to be a very sensitive marker for B lymphocytes in formalin-fixed, paraffin-embedded tissue. Most studies have found that the antibody is also highly specific for B cells, although a few examples of L26-positive T cell lymphoma (TCL) have been reported. We have studied L26 reactivity in 50 TCLs (all previously extensively immunophenotyped on frozen sections) and found positive labelling in 4 cases (3 pleomorphic, medium and large cell type with surface membrane staining; 1 T-anaplastic large cell type with cytoplasmic staining). The finding that L26 may give surface labelling in occasional TCLs (particularly of the pleomorphic, medium and large cell type) indistinguishable from that seen in B cell lymphomas emphasises the importance of always using diagnostic MAbs in combination if the risk of misinterpretation of lymphoma cell lineage is to be minimised. PMID- 2590535 TI - Gas chromatography of mycobacterial fatty acids and alcohols: diagnostic applications. AB - Capillary gas chromatography of cellular fatty acids and alcohols has been used as a routine method for a period of two years in the mycobacterial diagnostic laboratory of Statens institutt for folkehelse, Oslo, Norway. All mycobacteria (165 isolates) other than Mycobacterium tuberculosis (MOTT) and 24 randomly selected M. tuberculosis isolates were studied. Twelve characteristic lipid constituents allowed the construction of a diagnostic scheme. Without exceptions, all 36 examined isolates belonging to the M. tuberculosis-complex were characterized by a relatively high concentration level of hexacosanoic acid (mean: 4%, range: 1-13%), low level of tetracosanoic acid (mean: 1%, range: 0.1 3%), lack of methylbranched acids other than tuberculostearic acid, and lack of fatty alcohols. Members of the MAIS-complex (73 isolates) were all characterized by the general presence of the fatty alcohols 2-octadecanol (mean: 2%, range: 0.1 5%) and 2-eicosanol (mean: 7%, range: 2-21%), relatively high levels of tetracosanoic acid (mean: 5%, range: 1-15%) and lack (or trace) of hexacosanoic acid and methylbranched acids other than tuberculostearic acid. All 16 isolates of M. gordonae were easily recognized by their unique lack of tuberculostearic acid and their content of 2-methyl-tetradecanoic acid (mean: 5%, range: 2-12%), and the M. xenopi isolates were the only examined strains containing the fatty alcohol 2-docosanol (mean: 9%, range: 2-13%). The six M. malmoense strains contained the two unique constituents 2-methyl eicosanoic acid (mean: 3%, range: 1-4%) and 2,4,6-trimethyl tetracosanoic acid (mean: 3%, range: 2-4%). The ten strains of M. kansasii were characterized by 2,4-dimethyl tetradecanoic acid (mean: 5%, range: 1-11%), whereas the seven strains of M. marinum shared 2,4 dimethyl hexadecanoic acid (mean: 4%, range 0.2-12%) as a specific marker. PMID- 2590536 TI - Evaluation of Stuart's transport medium containing penicillinase. An in vitro study. Brief report. AB - An in vitro study was performed to evaluate the value of penicillinase in Stuart's transport medium. Swabs were taken from serum broth cultures of Staphylococcus aureus, Escherichia coli and Proteus rettgeri, incubated with cefuroxime. Following 24 hours' storage in the transport medium, the recovery of P. rettgeri was significantly higher from Stuart's transport media containing penicillinase in a concentration of 100,000 units/ml, than from swabs stored in Stuart's medium without penicillinase. Although susceptible to cefuroxime, we did not find the same effect on S. aureus and E. coli, presumably because these strains had higher MIC values than the P. rettgeri strain tested. PMID- 2590537 TI - Progress against cancer: are we winning the war? AB - The conclusion of two biostatisticians that 'with respect to cancer as a whole we have lost ground' was based on the rise in the age-standardized mortality from cancer. Trends in mortality at all ages combined may be misleading, as the effect of recent progress may be obscured by the effect of changes in the distant past on the incidence of cancer in old age. Recent progress is best assessed by examining trends at young ages, which can be affected only by relatively recent changes in treatment, behaviour, and the environment. These trends are mostly encouraging, but a few indicate a need for preventive action or research. PMID- 2590538 TI - Smoking and passive smoking in relation to lung cancer in women. AB - In a population based case-control study the association between female lung cancer and some possible etiological agents was investigated; 210 incident cases in Stockholm county, Sweden, and 209 age-matched population controls were interviewed about their exposure experiences according to a structured questionnaire. A strong association between smoking habits and lung cancer risk was found for all histological subgroups. Relative risks for those who had smoked daily during at least one year ranged between 3.1 for adenocarcinoma to 33.7 for small cell carcinoma in a comparison with never-smokers. All histological types showed strong dose-response relationships for average daily cigarette consumption, duration of smoking, and cumulative smoking. There was no consistent effect of parental smoking on the lung cancer risk in smokers. Only 38 cases had never been regular smokers and the risk estimates for exposure to environmental tobacco smoke were inconclusive. The high relative risks of small cell and squamous cell carcinoma associated with smoking may have implications for risk assessments regarding passive smoking. PMID- 2590539 TI - Monoclonal B-cells in blood in non-Hodgkin lymphoma. Correlation with clinical features and prognoses. AB - Presence of monoclonal B-cells in peripheral blood (MBCB) was studied in 132 previously untreated patients with non-Hodgkin lymphoma classified according to the Kiel classification. Detection of B-cells was performed by immunofluorescence microscopy, using antibodies against immunoglobulin light chains. Thirty-six patients (27%) were found to have MBCB. In the subgroup of low grade lymphomas 25/75 (33%) and in high grade lymphomas, 11/57 (19%) had MBCB. Presence of MBCB was correlated to clinical stage and 81% of the patients with MBCB were in stage IV. Twenty-two out of 36 (61%) patients with MBCB had normal lymphocyte counts (less than 5.0 X 10(9]. MBCB indicated a less favourable prognosis, mainly due to the close association with stage IV. It was concluded that studies of MBCB by this simple method are useful in detecting 'subclinical' blood involvement and valuable in the initial staging procedure as well as in the follow-up of the patients. PMID- 2590540 TI - CA 125 assay used in conjunction with CA 15-3 and TAG-72 assays for discrimination between malignant and non-malignant diseases of the ovary. AB - It has previously been suggested by the authors that elevated serum CA 125 levels may be of value in discriminating malignant from non-malignant pathologies among women with pelvic masses. Enhancement of this discrimination capacity might be achieved by utilizing additional serum assays. To test this hypothesis CA 125, CA 15-3 and TAG-72 levels were determined in double-blind fashion on 219 sera from patients undergoing diagnostic laparotomy for pelvic masses at six gynecological departments in the Stockholm area. Patient diagnoses were verified by chart review. Of the 219 patients, 27 (12%) had non-mucinous ovarian carcinoma, of whom 26 (96%) had CA 125 levels of 35 U/ml or greater 23 (85%) had levels in excess of 65 U/ml. Of 27 patients with mucinous or borderline ovarian carcinoma and patients with other malignancies 18 (67%) had CA 125 levels greater than 35 U/ml. Of 165 women with non-malignant diagnoses 26 (16%) had CA 125 levels in excess of 35 U/ml and 8 (5%) greater than 65 U/ml. Using reference values of 35 U/ml, 30 U/ml and 10 U/ml for the CA 125, CA 15-3 and TAG-72 assay respectively, only 3 of 165 (2%) of non-malignant patients were categorized as positive, compared to 23 of 27 (85%) of those with non-mucinous ovarian carcinoma. Moreover, an analysis of postmenopausal women revealed that the combination of assays--in a model controlling for the effect of CA 125--increased the specificity for diagnosis of benign diseases in women with pelvic masses. PMID- 2590541 TI - The role of restaging laparotomy in Hodgkin's disease. AB - The role of restaging laparotomy (RL) in Hodgkin's disease was studied in 41 patients. Two patients were in clinical stage I, 16 in clinical stage II, 13 in clinical stage III and 10 in clinical stage IV. Eight cases had previously received radiation therapy alone, 26 chemotherapy and 7 combined chemo-, and radiotherapy. The patients were divided into 2 groups, depending on the results of the preoperative clinical reevaluation. Group 1 included 20 patients with suspicion of persistent disease; in 6 (30%) RL was positive. Group 2 consisted of 21 cases with clinical appearance of complete response; RL was positive in one case (4.7%). The results of the comparison confirm the high rate of false positive findings in CT and lymphography. RL appears as a valuable procedure in patients with positive or doubtful clinical findings at reevaluation after radical therapy, in order to reduce the risk of unnecessary treatment. PMID- 2590542 TI - Phase II trial of mitozolomide in patients with advanced ovarian cancer. A study of the EORTC Gynecological Cancer Cooperative Group. AB - Twenty-seven fully evaluable patients with advanced ovarian cancer and documented disease progression despite cytotoxic treatment were treated with mitozolomide (NCS-353451) 90 mg/m2 as a 1-h infusion once every 6 weeks. None of the patients responded, one had stabilization of disease for 4 months. Haematologic toxicity was the major side effect with a nadir or white blood cell counts around day 40. Two patients died with severe leukopenia and septic shock. We conclude that mitozolomide is not active in this poor-risk group of patients. PMID- 2590543 TI - The effect of thoracic irradiation for cancer of the breast on ventilation, perfusion and pulmonary permeability. A one-year follow-up. AB - Regional and overall lung function was studied in 14 women during a one-year follow-up after postmastectomy irradiation for cancer of the breast. The dose was 40 Gy in the chest wall and 20-40 Gy in the apex of the lung. Immediately after irradiation there was a slight increase in pulmonary clearance of 99TCm-DTPA compared to baseline values. This increase, however, was not restricted to the field of irradiation. Three months after irradiation there were regional defects in the ventilation and perfusion scintigrams in 11 of the patients. At the same time there was a greater decrease in total lung capacity, vital capacity and diffusion capacity for CO than in ventilation and perfusion. One year after irradiation the lung function impairment had only insignificantly regressed. It is concluded that local lung irradiation may cause persistent regional and generalized lung function impairment. The early increase in pulmonary clearance of 99Tcm-DTPA could not be used as a predictor of subsequent lung function impairment. PMID- 2590544 TI - Reproducibility of field alignment in radiation therapy. A large-scale clinical experience. AB - A specially designed cassette which gives an excellent quality of portal films has been used to determine the set-up accuracy and uncertainties in treatment alignment during full-course radiation therapy on patients treated for some common malignant diseases. An analysis of a comparison between simulator films and portal films is also presented. For various diagnoses treatment-to-treatment positioning varied with an average standard deviation of 3.5 mm despite the use of laser alignment and good patient fixation. PMID- 2590545 TI - Vascular effects of photodynamic therapy in an intraocular retinoblastoma-like tumour. AB - Results from experimental tumours suggest that the mechanism of action of photodynamic therapy (PDT) involves both a direct killing of tumour cells, and a secondary effect resulting from vascular damage. We have investigated the possible vascular changes induced by PDT in an intraocular retinoblastoma-like rat tumour model using the 86RbCl extraction procedure. Light irradiation (90 J/cm2; 633 nm; 30 min) of intraocular tumours 24 h after an intraperitoneal injection of 5 mg/kg Photofrin II produced an increase in the tumour uptake of 86RbCl during the treatment period. However, 24 h later these values had decreased to 25% of that normally found in control animals. These effects were observed in both the tumour material and associated normal eye tissue, but not in PDT treated normal eyes without tumours. The results confirm that the vasculature of this eye tumour model is a target for some of the PDT effects. PMID- 2590546 TI - Kinetics of radioiodinated monoclonal antibodies in the rat. Influence of tumour growth and reticuloendothelial system host modulation. AB - This experimental study in rats examines the influence of tumour growth and RES function modulation on the kinetics of iodinated MAb IgG1 C241. The study was designed to investigate unspecific accumulation in liver and blood. C241 is raised against human colon adenocarcinoma COLO 205 and reacts with SiLea tumour associated antigen, also known as tumour-associated antigen 19-9. In 26 rats, 2 micrograms 125I MAb C241 (lodobead labelling method) was given i.v. Blood, organ and tumour content was measured at 0.5, 24, 72 and 144 h. In 61 rats, 10 micrograms 131I MAb C241 (lodogen labelling method) was given i.v. The rats were divided into a non-tumour and a tumour-bearing group and subjected to RES function modulation with Zymosan stimulation or methyl palmitate depression. A syngeneic nitrosoguanidine-induced colonic carcinoma--mean 11 g--was growing in back subcutaneous tissue and hind leg musculature. Serum content of tumour associated antigen was not found on IRMA testing and tumour content of SiLea ganglioside antigen was found only on lipid binding phase assay. The half-time in blood of iodinated MAb C241 was three days. In-vivo release of iodine was tested by plasma separation on a gel column. More than 90% of the iodine was in the IgG fraction. The activity distribution was almost in equilibrium after 24 h. A tumour/blood activity concentration ratio of 0.5 and liver/blood ratio of 0.3 remained at 72 h and 144 h. Radionuclide accumulation was equally low in the macrophage-rich liver and the kidneys. Tumour-bearing animals had significantly lower blood content (0.37 versus 0.99% g-1) and liver content (0.09 versus 0.31% g-1) at 144 h than non-tumour-bearing rats. The whole body content at 144 h was also lower (24% versus 35% of administered activity) (p = 0.10). Modulation of RES function had no significant influence on the whole body, blood or liver content of 131I MAb C241 activity in non-tumour-bearing animals. In tumour bearing animals, RES stimulation with Zymosan increased the whole body, liver and blood content of 131I activity. The two tested methods of iodination gave similar results. PMID- 2590548 TI - Pharmacokinetics and central haemodynamic effects of doxorubicin and 4'epi doxorubicin in the pig. AB - The relationship between the cardiotoxicity and the haemodynamics/pharmacokinetics of clinical concentrations of doxorubicin and 4'epi-doxorubicin was studied. Twelve pigs were randomized to receive i.v. infusions of either drug of 50 mg/m2 over 3.0 min. Aortic, pulmonary arterial, coronary sinus and central venous plasma concentrations of the agents were determined until 180 min after the infusion. The V5 ECG, left ventricular dP/dT, aortic, pulmonary arterial and right atrial pressures were recorded continuously, cardiac output and coronary sinus blood flow were recorded intermittently. No haemodynamic changes were recorded after administration of either drug. Pharmacokinetic data indicated myocardial extraction, followed by myocardial release of both drugs. This release was higher after administration of 4'epi doxorubicin than after doxorubicin, within the range 2-4 min and 20-40 min after the infusion. The tendency of greater myocardial release of 4'epi-doxorubicin may explain its lower cardiotoxicity. PMID- 2590547 TI - Comparative study of proportion of S-phase cells in ascites and pleural effusions in ovarian carcinoma using antibromodeoxyuridine monoclonal antibody and DNA flow cytometry. AB - Bromodeoxyuridine (Brd-Urd) was utilized in vitro to detect proliferating cells in 33 samples of ascitic and pleural effusions of ovarian malignancies and the results were compared with DNA flow-cytometry. Percoll separated tumor cells were incubated in vitro with Brd-Urd. After treatment with anti-Brd-Urd monoclonal antibodies the proportion of fluorescent cells was evaluated on slides by microscopy. A good correspondence (r = 0.93) was found between the proportion of cells labelled with Brd-Urd and the S-phase cells evaluated from the DNA histograms. S-phase values were found to be higher in tumors with aneuploid than in diploid DNA index. Poorly differentiated tumors had higher values as compared to moderately or well differentiated tumors. PMID- 2590549 TI - Bronchial carcinoid with a twenty-four-year natural history. A case report. PMID- 2590550 TI - Registration of liver cancer data--a study on the reliability of the Swedish Cancer Registry. PMID- 2590551 TI - Severe small bowel radiation enteritis. PMID- 2590552 TI - Cancer by the year 2000. Educational requirements for future oncologists. PMID- 2590553 TI - Serum reactivity to HIV-1 accessory gene products distinguishes East African from West African HIV strains as infecting agent. PMID- 2590554 TI - A rapid, quantitative bioassay based on the human immunodeficiency virus trans activator. AB - We constructed a human immunodeficiency virus (HIV) trans-activator cDNA (tat) encoding the N-terminal 76 amino acids of the viral trans-activator followed by two additional amino acids (val and pro). This cDNA encoded a functional trans activator (TAT) as shown by cotransfection into murine cells with a HIV promoter chloramphenicol acetyltransferase DNA construct. The tat cDNA was cloned into an avian retroviral expression vector, a modified spleen necrosis virus (SNV), and high-titer infectious stocks of recombinant virus (SNV-tat) were recovered from dog cells. Hybridization analyses indicated that SNV-tat was stably propagated in these cells for months. We also prepared recombinant cells that stably carry reporter genes, either a human gene encoding a soluble CD4 receptor (sCD4) or the human preprorenin gene, under the transcriptional control of the HIV promoter. Medium obtained from these cell cultures after infection with control viruses or an SNV carrying an antisense tat contained only low background levels of sCD4 or prorenin (HRN) as determined by specific immunoassays (1-10 ng protein per 10(6) cells per ml medium). In contrast, cells infected with SNV carrying tat in the transcriptional sense orientation secreted 75 +/- 7 ng sCD4 and 73 +/- 4 ng HRN per 10(6) cells per ml medium. Moreover, these proteins were constitutively secreted at these levels during months of subculturing. The data indicate that sCD4 and HRN are secreted from these cells because of a TAT-mediated trans activation of the HIV reporter gene DNA and/or RNA. This combination of recombinant cells, SNV-tat, and specific immunoassays provide a rapid, quantitative, and safe bioassay to seek inhibitors of TAT. PMID- 2590555 TI - ELISPOT: a new approach to studying the dynamics of virus-immune system interaction for diagnosis and monitoring of HIV infection. AB - A new approach to detect and enumerate HIV-specific antibody-secreting cells (ASC) in the peripheral blood was developed using the enzyme-linked immunospot (ELISPOT) methodology. ASC to an HIV envelope recombinant protein were demonstrated in 75% of 16 adults and 72% of 21 children with untreated AIDS or ARC and in 63% of 34 asymptomatically infected adults but in none of the 51 HIV antibody-negative individuals. Only 1 of the 13 adults receiving AZT therapy yielded a positive reaction, and 27% of the 30 infants born to seropositive mothers were found to have HIV-ASC. The number of HIV-ASC in positive individuals varied from 8 to 202 per 10(6) circulating mononuclear cells. The reactivity was specifically inhibited by soluble HIV antigen and was abrogated by cycloheximide, indicating that the observed reaction was the result of de novo synthesis of HIV specific antibodies. Nonspecific polyclonal B cell activation was unlikely to be responsible for the results observed as no reactivity was found to a common antigen, tetanus toxoid. Since circulating antigen-specific ASC reflect persistent or recent antigenic stimulation, our findings indicate that this new approach could provide a dynamic perspective of the natural course of virus immune system interactions in individuals infected with HIV, as well as in those undergoing prophylactic or therapeutic interventions. PMID- 2590556 TI - Cross-neutralizing antibodies against HIV-1 (HTLV-IIIB and HTLV-IIIRF) and HIV-2 (SBL-6669 and a new isolate SBL-K135). AB - A total of 57 HIV-1 antibody-positive sera and 43 HIV-2 antibody-positive sera were all tested for neutralizing capacity against two HIV-1 isolates (HTLV-IIIB and HTLV-IIIRF) and two HIV-2 isolates (SBL-6669 and SBL-K135). SBL-K135 is a new HIV-2 isolate obtained from a patient with clinical AIDS from Guinea-Bissau. Among the HIV-1--positive sera, 84% neutralized any of the HIV-1 isolates, 67% neutralized both HIV-1 isolates, and 35% neutralized any of the HIV-2 isolates. Among the HIV-2--positive sera, 91% neutralized any of the HIV-2 isolates, 67% neutralized both HIV-2 isolates, and 37% neutralized any of the HIV-1 isolates. Thus, neutralizing antibodies in HIV-1-- and HIV-2--positive sera can be cross reacting, type-specific, or strain-specific. The cross-neutralizing titers were lower than the neutralizing titers against the type-specific viral isolates. The presence of cross-neutralizing antibodies was related to the presence of neutralizing antibodies against both type-specific isolates. PMID- 2590557 TI - Uptake of 2',3'-dideoxyadenosine in human immunodeficiency virus-infected and noninfected human cells. AB - The uptake of 2',3'-dideoxyadenosine was examined in a human immunodeficiency virus (HIV) infected and uninfected T cell line (H9 cells), a B cell line (Namalwa), and in normal peripheral blood mononuclear cells. After a 10-minute incubation at ambient temperature, the intracellular 2',3'-dideoxyadenosine derived radioactivity was 8- to 16-fold higher than the extracellular radioactivity. In metabolically inactive cells (0 degrees C), the intracellular and extracellular 2',3'-dideoxyadenosine-derived radioactivities were nearly equal. In infected and noninfected H9 cells, a large excess of p nitrobenzylmercaptopurine riboside or pyrimidine nucleosides weakly inhibited the uptake of 2',3'-dideoxyadenosine (7-30%), whereas deoxycoformycin was a stronger inhibitor (50-80%). Purine nucleosides minimally enhanced the uptake (10-20%). The cellular uptake was not associated with the accumulation of dideoxyadenosine triphosphate. In normal peripheral blood mononuclear cells, the uptake of 2',3' dideoxyadenosine was inhibited by all agents except 2'-deoxyadenosine (15% enhancement). In contrast to H9 cells, the formation and accumulation of dideoxyadenosine triphosphate paralleled the uptake of dideoxyadenosine. The results of these studies suggest that the major route of transport of 2',3' dideoxyadenosine into cells is by simple diffusion and that different metabolic patterns exist among cell lines and normal peripheral blood mononuclear cells. An understanding of these cellular differences could aid in the development of therapeutic strategies directed against HIV. PMID- 2590558 TI - High prevalence of serum antibody against human T cell leukemia virus type I (HTLV-I) among the Bismam Asmat population (Indonesian New Guinea). AB - An unusually high prevalence (45%) of serum antibodies to human T cell leukemia virus type I (or to an antigenically related virus) in comparison with that observed against other viral pathogens (human immunodeficiency virus type 1, herpes simplex virus, human cytomegalovirus, varicella zoster virus, and respiratory syncytial virus) has been observed in a group of Bismam Asmat (Papua) subjects, living in a very limited and geographically isolated area of Indonesian New Guinea. PMID- 2590559 TI - [Growth factors produced by rat glioma cells: activities of transforming growth factors]. AB - Growth factors contained in cultured medium of rat glioma C6 cells (C6 cells) were examined mainly for the activity of transforming growth factors (TGFs). Cultured medium of C6 cells was dialyzed against acetic acid, lyophilized and chromatographed by gel-permeation method, the fractions were assayed by soft agar colony formation, iodine 125 (125I)-epidermal growth factor (EGF)-binding competition and incorporation of tritium-thymidine. Two nontransformed cell lines, clonal NRK49F and BALB/3T3 A 31-1-1 (3T3) cells, were used as indicator cells for the soft agar colony assay. 3T3 cells were also used for the incorporation of tritium-thymidine. EGF receptor-rich A 431 cells were used for 125I-EGF-binding competition assay. The activity of alpha-type TGFs was examined by soft agar colony formation of NRK49F cells and inhibition of EGF-binding to A 431 cells since TGF alpha has sequence homology with EGF and binds to EGF receptors on the cell membrane, while the activity of beta-type TGFs was examined by soft agar colony formation of 3T3 cells and NRK 49 F cells with the addition of EGF. High level of activities of both TGF alpha and TGF beta were detected in 14,000 to 45,000 daltons, and also high level of the activity of DNA synthesis was detected at the same molecular weight. These results suggest that C6 cells produce TGF alpha and TGF beta as well as platelet-derived growth factors (PDGFs) analogue. Since amplification of EGF receptor gene has been demonstrated in glioma, TGF alpha released by glioma may provide autocrine stimulation through the binding to the amplified EGF receptors. TGF beta is known to increase EGF receptors on the cell membrane. TGF beta has been demonstrated not only to stimulate but also inhibit cell proliferation under certain circumstances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590560 TI - [The effect of local injection of interferon against human malignant glioma transplanted into nude mice and the mechanism of its effect]. AB - In order to clarify the mechanism of action of recombinant human leucocyte interferon, the effect of local injection of it to the human malignant gliomas (one oligodendroglioma, the other glioblastoma) transplanted into nude mice were evaluated. The volume of the tumors were calculated as 1/2 (short diameter [cm])2 x (long diameter[cm]). And the ratio of tumor volume (T)/original size (C) were calculated in terms of experimental day. Among the groups of control (vehicle of IFN injected), 1 million units of IFN locally injected group, 3 million units injected group, and 9 million units injected group, the effects of the treatment were statistically evaluated in terms of T/C. At the end of the experiment, each animal was injected 4 mg of BrdU intraperitoneally, and the labeling indices of the tumor tissue were measured and compared among the groups above mentioned. Local injection of IFN to the tumor was effective even at the dose of 1 million units every other day for 16 days for glioblastoma and 50 days for oligodendroglioma. The labeling index of the treated groups was significantly reduced when compared to that of control group in both tumors. And the experiment was performed to evaluate the variation of NK activity and ADCC activity of mouse spleen cells among the experimental groups. For the oligodendroglioma, NK activities were significantly increased in the 9 million units of IFN injected group when compared to those of control group. For glioblastoma, there was no definite variation of NK and ADCC activities among the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590561 TI - [Regional cerebral blood flow and oxygen consumption during normal human sleep]. AB - Regional cerebral blood flow (rCBF), regional oxygen extraction fraction (rOEF) and regional cerebral metabolic rate for oxygen (rCMRO2) were measured using the continuous inhalation technique for 15O with positron emission tomography (PET) during both wakefulness and sleep. Ten paid volunteers, with a mean age of 21.6 yrs., were deprived of sleep for a period of approximately 20 hours, and the experiments were performed mostly in the morning. 15O activity of both whole blood and the plasma, pixel count of PET, total arterial blood oxygen content were used for analysis of rCBF, rOEF and rCMRO2. PET scannings were carried out mostly during the very light non-rapid eye movement (NREM) sleep, i.e. stage 1 and/or 2, and wakefulness. About 10 minutes after the start of continuous inhalation of 15O gas, the 15O activity of the brain was found to be in a steady state condition. During this steady-state condition, PET scannings were performed for about 10 minutes. Regions of interest, square in shape and having an area of 2.8 cm3, were set in each cortex on PET images of a horizontal cross-section of the brain, set at 45 mm above the orbitomeatal line. The rCBF and rCMRO2 were analysed in 5 of 10 male subjects during both wakefulness and NREM sleep, and only 3 were done during three sleep stages, including REM sleep. Levels of rCBF and rCMRO2 were found to be decreased in NREM sleep, and the decreasing rates were calculated at 10.2% and 7.6% from the level of wakefulness, respectively. There was no significant difference in the mean value of rOEF between wakefulness and NREM sleep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590562 TI - [Chemotherapeutic strategy in rat brain tumor cells resistant to ACNU using an in vitro colony formation assay]. AB - Nitrosourea compounds have been widely used in the chemotherapy of malignant brain tumors, because of their blood-brain barrier permeability. However, drug resistance to nitrosoureas has been recently a major concern. Using an in vitro colony formation assay, intrinsic and acquired resistances to an anticancer nitrosourea, 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3 nitrosourea hydrochloride (ACNU), were analyzed in rat 9L and C6 glioma cells. 9L and C6 cells were treated with varying doses of ACNU for 2 hours. Ten days after, the cells were fixed and stained with crystal violet. Colonies consisting more than 50 cells were counted. The survival fraction following treatment is the ratios of colony efficiency of treated cells to the colony efficiency of untreated control cells. The dose-response curve for ACNU indicated the existence of a shoulder (Dq, quasithreshold dose) at doses and an exponential cell-killing at higher doses with D0(37% survival dose). Based on dose-response curves corresponding to multitarget single-hit model, 9L cells showed 7.4 microM, 2.9 microM, and 14 microM at Dq, D0, and SD10 (10% survival dose) values, respectively, whereas C6 cells showed respective values of 6.4 microM, 30 microM, and 75 microM. 9L cells had significantly less intrinsic resistance to ACNU than C6 cells at the p less than 0.005 level by a covariance analysis of the curves. As with changes of drug susceptibility after ACNU treatment, both parent cells were treated every other day (1, 5, and 10 repeated times) with various doses up to approximately 1% survival dose of the parent cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590563 TI - President's address to the General Dental Council. PMID- 2590564 TI - Foetotoxic effects of mercury vapour. PMID- 2590565 TI - 'Needlestick injuries to dental staff'. PMID- 2590566 TI - 'Audit--a cause for TMJ dysfunction'. PMID- 2590567 TI - 'The title 'Dr' for the dentist'. PMID- 2590568 TI - Time for a change. PMID- 2590569 TI - Applications and admissions to UK dental schools through UCCA: 1968-1987. AB - Applications and admissions to UK dental schools through the UCCA system have been analysed for the 20-year period from 1968 to 1987. Applications rose from 1225 in 1968 to a peak of 3065 in 1974. By 1987, applications had fallen to 2050, 67% of the peak number. The ratio of male:female applicants has declined from 4:1 in 1968 to 1.6:1 in 1987. The number of dental students accepted through UCCA has varied much less during the 20-year period, rising from 831 in 1968 to a peak of 989 in 1980, and falling back to 893 in 1987. The number of dental students admitted to dental schools through UCCA in the 4 years including and after 1984 was 7.4% less than in the 4 years prior to 1984. This suggests that the 1984 cut of 10% was not fully achieved. The ratio of male:female students admitted has fallen from 3.4:1 in 1968 to 1.4:1 in 1987. In every year studied, the male:female ratio of UCCA applicants was higher than for accepted dental students. This could suggest that female applicants to dental school have higher academic or personal qualities than their male counterparts. PMID- 2590571 TI - Reye's syndrome and analgesic choice in dentistry. AB - In the light of recent warnings on the hazards of aspirin administration to children, a survey amongst the parents of 361 randomly selected child dental out patients, aged 11.99 years and under, was undertaken to determine their analgesic of choice for the relief of dental pain. A significant number of parents are continuing to administer aspirin to children under 12 years of age, contrary to medical advice. The choice of a suitable alternative analgesic is discussed. PMID- 2590570 TI - Pressures produced in vitro during intraligamentary anaesthesia. AB - An in vitro investigation measured the pressures produced by an Astra type aspirating syringe (modified Sterling) and a pressure syringe (Ligmaject) during periodontal ligament injections. A pressure transducer (0-6.9 MPa) was adapted to record the pressures generated within both syringes, with the output of the transducer connected to a microcomputer. Thirty-five clinicians (male: female ratio 3:2) were instructed in the technique of the periodontal ligament injection and the pressures that they produced from both syringes were recorded. Measurements of both the peak and time averaged pressures were obtained from computer print-outs of the recordings. Significantly higher pressures (P less than 0.01) were produced with the pressure syringe than with the aspirating syringe. It was also found that male operators produced significantly (P less than 0.1) higher pressure with the aspirating syringe, although there was no significant sex difference (P greater than 0.1) between the pressures recorded with the pressure syringe. Recordings from the pressure syringe revealed that either a multiple high pressure technique or a steady pressure technique was used, the former producing significantly (P less than 0.01) higher pressures. PMID- 2590572 TI - Teaching resuscitation--can we improve? AB - In 1987, a Working Party Report from the Royal College of Physicians addressed the record of resuscitation from cardiopulmonary arrest. Their stated aim was to identify groups for instruction and to determine how required skills should be taught and retained. The recommendation for our specialty was brief: '...trained and competent in basic life support with airway adjuncts'. A survey of local practitioners was undertaken, to study their use of general anaesthesia, intravenous sedation, and relative analgesia and to discuss their resuscitation arrangements. PMID- 2590573 TI - HIV update. PMID- 2590575 TI - The title 'doctor' for the dentist. PMID- 2590576 TI - From a grateful dentist. PMID- 2590574 TI - 'Friends of the FDI'. PMID- 2590577 TI - Untoward effects. PMID- 2590578 TI - 'The position of the inferior dental canal and its relation to the second molar'. PMID- 2590579 TI - Informed consent. PMID- 2590580 TI - Sugars: the autumn issue. PMID- 2590581 TI - Needlestick injuries to dental staff. PMID- 2590582 TI - Fee scales. PMID- 2590583 TI - Tooth transplant record. PMID- 2590584 TI - Bacteraemia and tissue damage resulting from air polishing. AB - This study investigates the production of bacteraemia in dental prophylaxis by use of a commercially available air polishing device. Prophylaxis by means of the conventional rubber cup and paste method was used as a control. The study showed that air polishing can result in loss of epithelium at the gingival margin. The likelihood of a bacteraemia resulting from air polishing, in the absence of gingivitis, was less than in the group undergoing conventional prophylaxis. Although a higher number of bacteraemias was seen in the control group, the difference between the two groups was not statistically significant. Results indicate that patients who are at risk continue to require antibiotic cover. PMID- 2590585 TI - Massive giant cell epulis in a child with familial cyclic neutropenia. AB - A case of a boy with familial cyclic neutropenia and a large giant cell epulis is reported. The clinical management is described and the significance of the neutropenia in relation to subsequent infection of the epulis is discussed. PMID- 2590586 TI - Changes in the flow properties of white blood cells after acute myocardial infarction. AB - Because they can obstruct blood vessels and release noxious substances, white blood cells may contribute to the development of tissue ischaemia. The flow properties of white cells were tested after myocardial infarction, by measuring the filtration rates of cell suspensions through 8 microns pore filters. Compared with mononuclear cells from age matched controls, mononuclear cells from patients with infarction showed impaired filterability within the first day after the onset of pain; this condition persisted for at least two days and by day 10 it was improved. On day 1, granulocyte filterability and the proportion showing morphological evidence of activation were nearly normal. By day 3 the flow resistance and activation had increased, but the changes seen depended on the age of the patient. The filterability and activation of granulocytes from patients aged less than 60 were significantly increased from day 1, whereas there were no changes in granulocytes from patients aged greater than 60 years. Suspensions of unfractionated white cells showed changes intermediate between the mononuclear cells and granulocytes. A group of five patients who presented with chest pain but who were subsequently found not to have had an infarction showed no evidence of abnormal filterability or activation. The changes in filterability probably reflect white cell activation, which may have an adverse effect on the perfusion of the ischaemic myocardium. PMID- 2590587 TI - The epicardial electrogram: a quantitative assessment during balloon angioplasty incorporating monophasic action potential recordings. AB - An electrogram was recorded from the angioplasty catheter guide wire when coronary blood flow was interrupted in 20 patients undergoing percutaneous transluminal coronary angioplasty. Monophasic action potentials were recorded from the right ventricular septum together with the routine electrocardiogram. The patients were studied during angioplasty for lesions in the left anterior descending (12), circumflex (3), and right coronary arteries (6). ST elevation in the electrogram recorded in the left anterior descending and circumflex systems was usually more obvious than that in the electrocardiogram. Signals obtained from the right coronary artery were of very low amplitude and registered only minimal ST changes. The ST elevation developed in the electrogram during insertion of the catheter before inflation of the balloon in 11 of the 15 patients undergoing angioplasty of the left system. In eight of the patients showing pre-inflation ST elevation the ST shift lessened after successive inflations. Monophasic action potential recordings were obtained during 45 balloon inflations in 19 patients. In those patients undergoing angioplasty for lesions of the circumflex coronary artery the monophasic action potential showed no change during balloon inflation. In patients undergoing angioplasty for the right coronary artery the mean normalised duration at 60 seconds' occlusion was 99.6 (1.5)% of control. Of a total of 25 occlusions in the patients undergoing angioplasty for the left anterior descending coronary artery 19 showed shortening of less than 5%, five showed shortening between 5 and 10%, and one showed a shortening of 16.4% in the monophasic action potential. The QT interval was satisfactorily measured in the electrogram during 36 balloon inflations, and in 24 of these it was also measured in the electrocardiogram. QT changes in the electrogram tended to be the opposite of those in the electrocardiogram. When changes in RR interval were minimal (less than 20 ms) during the balloon inflation 14 of 17 electrograms showed QT prolongation but only one of 12 electrocardiograms showed prolongation. Conversely one of 17 electrograms showed shortening compared with eight of 12 electrocardiograms. There was angiographic evidence of the development of collaterals in six of 15 patients undergoing angioplasty of the left system. ST segment elevation in both the electrogram and electrocardiogram was less pronounced in these patients than in those without evidence of the development of collaterals. ST segment changes recorded from the angioplasty guide wire provide a more sensitive index of ischaemia than the surface 12 lead electrocardiogram, and fall in ST segments on balloon deflation is a prognostic index of a good angiographic result in the left anterior descending and circumflex arteries, but not in the right coronary artery. PMID- 2590588 TI - Transvenous ablation of atrioventricular conduction with a low energy power source. AB - A power source modified to increase voltage delivery and minimise arcing (for a given energy) was used for transvenous ablation of atrioventricular conduction to control refractory supraventricular arrhythmias in 14 patients. Twelve had atrial fibrillation or flutter, one had atrioventricular nodal reentry tachycardia, and the other had permanent junctional reentry tachycardia. Despite treatment with 5 7 (median 6) antiarrhythmic drugs symptoms had persisted in all the patients. Cathodal discharges of 0.5-39.5 J were delivered to the distal electrode (in one case in parallel with the middle electrode). In all patients shocks produced complete atrioventricular block; this was permanent in eleven (79%). Four patients required a second procedure. In one patient, only a transient atrioventricular block could be produced and catheter ablation with a conventional power source also failed. In the other two atrioventricular conduction was modified such that previously ineffective treatment produced satisfactory control of heart rate. The cumulative energy delivered to those in whom permanent complete heart block resulted ranged from 3.6 to 97.8 (mean 38.3) J with a mean of three shocks (range 1-7) delivered per patient. During follow up of 1-28 (mean 14) months 11 patients remained in complete heart block and free of arrhythmia. PMID- 2590589 TI - Clinical efficacy of intravenous amiodarone in the short term treatment of recurrent sustained ventricular tachycardia and ventricular fibrillation. AB - The clinical efficacy of intravenous amiodarone in terminating sustained ventricular tachycardia and in preventing recurrences of ventricular tachycardia and ventricular fibrillation was evaluated in 26 patients. All of them presented with organic heart disease accompanied by depressed left ventricular function. Intravenous amiodarone terminated spontaneous ventricular tachycardia in eight of 19 patients. Fifteen of the 26 patients had had at least one episode of ventricular tachycardia or ventricular fibrillation each day in the period immediately before the intravenous administration of amiodarone. Amiodarone controlled ventricular tachycardia or ventricular fibrillation in nine of these 15 patients; in three further cases it was successful when supplemented by additional administration of a previously ineffective antiarrhythmic drug and ventricular pacing. Two patients died despite these measures. In one, the amiodarone infusion had to be stopped because of an arrhythmogenic effect. Sustained deterioration of haemodynamic function or of pre-existing intraventricular conduction disturbances was never seen. Intravenous amiodarone was effective in terminating sustained ventricular tachycardia and in preventing frequent episodes of ventricular arrhythmia that were refractory to other antiarrhythmic drugs. PMID- 2590591 TI - Hypertrophic cardiomyopathy in identical twins. AB - Hypertrophic cardiomyopathy was diagnosed in identical twin boys in early childhood. One underwent myomectomy at the age of 12 years because of progressive severe exertional dyspnoea accompanied by considerable obstruction of the left ventricular outflow tract shown on both echocardiography and cardiac catheterisation. Seven years later, at the age of 19, he remains incapacitated to a moderate degree. By contrast, the other twin has led a relatively normal life to date and no left ventricular outflow obstruction has been shown. PMID- 2590590 TI - HLA antigens in idiopathic dilated cardiomyopathy. AB - Disturbances of humoral and cellular immunity are common in patients with idiopathic dilated cardiomyopathy and they may contribute to the initiation and maintenance of myocardial damage. HLA antigens were studied in 102 patients with dilated cardiomyopathy and a control hospital population. HLA-DR4 was significantly more common in patients with idiopathic cardiomyopathy (41 patients, 40%) than in the control group (123 patients, 24%). The distribution of other antigens was not significantly different in the two groups. The distribution of blood group antigens, immunoglobulin concentrations, and disease severity was similar in patients with the HLA-DR4 antigen and those without it. These results suggest that HLA-DR4 antigen may be a genetic marker for susceptibility to dilated cardiomyopathy. PMID- 2590592 TI - Anomalous origin of one pulmonary artery from the ascending aorta: a review of echocardiographic, catheter, and morphological features. AB - Six patients with anomalous origin of one pulmonary artery from the ascending aorta were reviewed. Four had anomalous origin of the right pulmonary artery and two had anomalous origin of the left pulmonary artery from the ascending aorta. Two of these six patients had tetralogy of Fallot. Two patients died in the first month of life. No changes in the pulmonary vasculature were seen at necropsy. Corrective surgery was attempted in two patients with associated tetralogy of Fallot when they were two years old but both died. At necropsy there was severe pulmonary vascular disease in the lung supplied by the anomalous pulmonary artery but no pulmonary vascular hypertensive changes in the lung supplied by the pulmonary artery from the right ventricle. Two recent patients underwent successful anastomosis of the anomalous pulmonary artery to the main pulmonary artery at three months and one month and three weeks of age respectively. Intraoperative lung biopsy in the latter patient showed early changes in both lungs. Both echocardiography and cardiac catheterisation were used in the diagnoses. Systemic or suprasystemic pressures were found in the pulmonary artery arising from the right ventricle as well as the anomalous pulmonary artery in the three patients without tetralogy of Fallot. Anomalous origin of a pulmonary artery from the ascending aorta is a distinct entity and differs from other aorto pulmonary arterial connections. Early surgical intervention is recommended in all patients (including those patients with associated tetralogy of Fallot) because of the risk of rapid development of irreversible pulmonary vascular disease. PMID- 2590594 TI - Successful repeat percutaneous transluminal coronary angioplasty after failed coronary artery surgery for left main coronary artery dissection. AB - A 57 year old man required emergency coronary artery bypass surgery after dissection of the left main coronary artery during percutaneous transluminal coronary angioplasty. His symptoms recurred when the vein grafts became occluded. A dilatation device with the lowest profile was used to reduce the need for firm support from the guiding catheter during repeat percutaneous transluminal coronary angioplasty. The repeat procedure was successful in opening up the left circumflex coronary artery. PMID- 2590593 TI - Recurrent ventricular tachycardia associated with anomalous left coronary artery from the pulmonary artery in a child managed by revascularisation and map-guided endocardial resection. AB - A 13 year old girl with recurrent ventricular tachycardia that occurred in association with anomalous origin of the left coronary artery from the pulmonary artery is described. Such an arrhythmia has not been described before. Ligation of the anomalous left coronary artery led to more frequent episodes of ventricular tachycardia with evidence of myocardial ischaemia. She was successfully managed by revascularisation (to establish a two coronary system) and map-guided left ventricular aneurysmectomy. PMID- 2590595 TI - Spontaneous displacement of a pacemaker electrode and its subsequent successful reimplantation. AB - A case of what was assumed to be twiddler's syndrome was caused by spontaneous twisting and displacement of the electrode on the fortieth postoperative day. The pacemaker had not been manipulated by the patient, the pocket was tight, and the proximal electrode was well secured. The complication was managed successfully by reimplanting the same electrode after stiffening the lead near the generator with a portion of the stylet. PMID- 2590596 TI - Congenital fistula between the left ventricle and coronary sinus: elucidation by colour Doppler flow mapping. AB - A fistula between the left ventricle and the coronary sinus was diagnosed by Doppler echocardiography and confirmed by cardiac catheterisation in a symptom free child who presented with clinical signs of mitral regurgitation. A similar abnormality has been reported after repeated mitral valve replacement and after myocardial infarction but a congenital fistula of this type has not been described before. PMID- 2590597 TI - Heart transplantation for Churg-Strauss syndrome. AB - A patient with heart failure caused by Churg-Strauss syndrome was successfully treated with transplantation. The case was unusual because there was little evidence of Churg-Strauss syndrome in the lung. The patient remains well on standard transplant immunotherapy. PMID- 2590598 TI - Changes in transmitral velocities with heart rate. PMID- 2590600 TI - Bioactivation of dapsone to a cytotoxic metabolite by human hepatic microsomal enzymes. AB - 1. Using human mononuclear leucocytes as target cells, we have investigated the bioactivation of dapsone (DDS) to a cytotoxic metabolite in the presence of microsomes from nine human livers. Values for NADPH dependent toxicity ranged from 8.8-27% (15.8 +/- 5.9%) and were similar to those for microsomes from control mice, 16-24% (19.0 +/- 4.8%). 2. Microsomes prepared from mice induced with either phenobarbitone or beta-naphthoflavone did not produce significantly more NADPH dependent toxicity than microsomes prepared from control mice. 3. Cytotoxicity was abolished not only by ascorbic acid, but also by sub physiological concentrations of N-acetylcysteine and glutathione. 4. DDS was metabolised in vitro to a hydroxylamine (metabolic conversion 3.1 +/- 1.5%), which was oxidised further to a cytotoxic metabolite which also became irreversibly bound to protein. PMID- 2590601 TI - The effect of phentolamine on basal and pethidine-induced inhibition of gastric emptying in healthy volunteers. AB - 1. The effect of phentolamine 5 mg i.v. on basal and pethidine-induced inhibition of gastric emptying of semisolid TC-99m labelled Chelex-100 resin/oatmeal was studied in ten healthy volunteers. 2. Each volunteer acted as his/her own control. 3. Basal gastric emptying remained unchanged after administration of phentolamine. 4. Administration of phentolamine reversed the pethidine-induced inhibition of gastric emptying. PMID- 2590599 TI - The increase in urinary excretion of 6 beta-hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction. AB - 1. Urinary excretion of 6 beta-hydroxycortisol, hepatic microsomal cortisol 6 beta-hydroxylase and the specific content of several forms of cytochrome P450 were measured in 8 to 14 patients before and after treatment with rifampicin (600 mg orally per day for 4 days). 2. Rifampicin treatment produced an average five fold increase in daily excretion of urinary 6 beta-hydroxycortisol. 3. Cortisol 6 beta-hydroxylase activity increased from 15 +/- 6 pmol min-1 mg-1 in organ donors (considered as 'control subjects') to 87 +/- 31 pmol min-1 mg-1 in rifampicin treated patients. 4. Among three forms of human P450 (P450IA, IIC and IIIA), (1), (2), measured by Western blots, only P450IIIA was significantly induced by the antibiotic. 5. Only antibodies against P450IIIA selectively inhibited cortisol 6 beta-hydroxylase in human liver microsomes. 6. Cortisol 6 beta-hydroxylase was correlated with P450IIIA specific content. 7. The urinary level of 6 beta hydroxycortisol correlated with liver microsomal cortisol 6 beta-hydroxylase and P450IIIA specific content. 8. We conclude that P450IIIA is predominantly responsible for cortisol 6 beta-hydroxylase activity in human liver microsomes and that urinary 6 beta-hydroxycortisol is a marker of the induction of this cytochrome P450. PMID- 2590602 TI - A comparison of the ocular hypotensive effect of 0.025% bromocriptine and 0.25% timolol eye drops in normal human volunteers. AB - 1. The ocular hypotensive effect of 0.025% bromocriptine and 0.25% timolol eye drops was compared in nine healthy human volunteers, using non-contact tonometry. 2. Considering all post-dosing measurements compared with placebo and including the baseline values as continuous independent variables, using multiple linear regression analysis, both bromocriptine and timolol had a significant ocular hypotensive effect (P less than 0.0001) in the treated eye with a significant but lesser effect in the contralateral eye. 3. In the concentrations used, timolol was more efficacious than bromocriptine in lowering intraocular pressure (P less than 0.025). 4. Using other forms of vehicles for bromocriptine to improve efficacy and studying the ocular hypotensive effect of topical application of other dopamine-2-receptor agonists such as pergolide and lisuride was suggested. PMID- 2590603 TI - Salicylate pharmacokinetics in patients with rheumatoid arthritis. AB - 1. The pharmacokinetics of salicylic acid (SA) and its major metabolite salicyluric acid (SU) were studied in nine patients with rheumatoid arthritis following a 900 mg oral dose of acetylsalicylic acid and during 6 weeks of chronic administration of enteric coated aspirin (3,900 mg day). Response to therapy was also monitored. 2. The various pharmacokinetic parameters determined in the study were similar to those observed in other single dose salicylate studies amongst healthy volunteers but were not predictive of salicylate concentration in the chronic dose study. 3. Plasma concentrations of SA (total and unbound) were found to decline significantly over the 6 weeks and plasma SU concentrations increased. 4. During the chronic dosing study, there was a significant increase in the Vmax (total and unbound) for the formation of SU, whilst the Km and SU clearance remained constant. Also, the elimination rate constant (k) for salicylate was not significantly affected. 5. Therapeutic response to salicylate therapy was not significantly affected by the decline in SA concentrations. PMID- 2590604 TI - Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in young and elderly volunteers after single and multiple dextropropoxyphene dosage. AB - 1. The pharmacokinetics of dextropropoxyphene (D) and nordextropropoxyphene (ND) have been studied in 12 healthy young (21-28 years) and 12 healthy elderly (70-79 years) male and female subjects. Each received 65 mg D and plasma D and ND concentrations were measured by h.p.l.c. with electrochemical detection for up to 7 days and again after 65 mg D, 3 times daily for 1 week. 2. There were no significant differences in median D and ND half-life, AUC, Cmax and tmax between the male and female subjects in either group. Within the groups the mean D half life (h) was longer in the young after multiple dosing (mean +/- s.d.:13.2 +/- 5.2 and 23.7 +/- 11.3, P less than 0.05, paired t-test) but there were no other significant differences. 3. Between the groups, the median single and multiple dose D and ND half-lives were all significantly longer (P less than 0.02) and the median D AUC for both single and multiple doses was significantly higher (P less than 0.01 and P less than 0.05, respectively, Mann-Whitney U-tests) in the elderly. 4. There was no relation between multiple dose Cmax and other parameters such as single dose D half-life. However, across the groups D and ND half-lives after both single and multiple dosage correlated significantly with estimated creatinine clearance, the correlation being strongest with ND (r = -0.76 and 0.84, respectively). PMID- 2590605 TI - Bioelectrical impedance modelling of gentamicin pharmacokinetic parameters. AB - 1. Bioelectrical impedance analysis was used to develop descriptive models of gentamicin pharmacokinetic parameters in 30 adult in-patients receiving therapy with gentamicin. 2. Serial blood samples obtained from each subject at steady state were analyzed and used to derive gentamicin pharmacokinetic parameters. 3. Multiple regression equations were developed for clearance, elimination rate constant and volume of distribution at steady state and were all statistically significant at P less than 0.05. 4. Clinical validation of this innovative technique is warranted before clinical use is recommended. PMID- 2590606 TI - Gentamicin volume of distribution as a power function of body weight. AB - Gentamicin volume of distribution (V) was related to body weight (W) in 183 obese, normal weight and infant patients as reported in five published studies. In contrast to the usually postulated simple proportionality (V = bW) a linear function was found (V = a + bW) with an intercept (a = 2.5 +/- 0.49) significantly different from zero (P = 0.0001) and a slope (b = 0.19 +/- 0.10) significantly different (P = 0.0001) from the mean factor of proportion (b = 0.35 +/- 0.19). As compared with the linear function, a power function (V = 0.57 W 0.79) approximated even more closely the dependence of gentamicin volume on body weight (r = 0.94 vs r = 0.81). The difference between both functions was more than 50% only for body weight less than 5 kg. It is concluded that the relation between gentamicin volume of distribution and body weight is non-linear. PMID- 2590607 TI - Structural requirements for bioactivation of anticonvulsants to cytotoxic metabolites in vitro. AB - The formation of cytotoxic metabolites from the anticonvulsants phenytoin and carbamazepine was investigated in vitro using a hepatic microsomal enzyme system and human mononuclear leucocytes as target cells. Both drugs were metabolised to cytotoxic products. In order to assess the structural requirements for this bioactivation, a series of structurally related compounds was investigated. It was found that molecules which contain either an amide function or an aryl ring may undergo activation in vitro, but only the metabolism-dependent toxicity of the latter is potentiated by pre-treatment of the target cells with an epoxide hydrolase inhibitor. Taken collectively, these data are consistent with the concept that reactive epoxide metabolites of both phenytoin and carbamazepine may produce toxicity in individuals with an inherited deficiency in epoxide hydrolase. PMID- 2590608 TI - Effect of oxpentifylline on blood viscosity and cerebral blood flow in man. AB - The effects of intravenous oxpentifylline on blood viscosity and cerebral blood flow were studied in eight patients with cerebrovascular disease using a double blind placebo controlled design. A single dose of 200 mg oxpentifylline in 10 ml saline was given by intravenous injection over 10 min and compared with 10 ml saline alone. Whole blood and plasma viscosity were measured in a Contraves LS 30 coaxial viscometer at shear rates of 0.7 and 94.5 s-1. Cerebral blood flow was measured by the non-invasive intravenous xenon133 clearance method. The measurements were made before and then 30 min after the start of the injection of drug or saline alone. Oxpentifylline was found to have no significant effect on blood viscosity or cerebral blood flow. PMID- 2590609 TI - An observation on the ethnic uniqueness of the debrisoquine and sparteine antimodes: a study in the Ngawbe Guaymi Amerindians of Panama. PMID- 2590610 TI - Psychomotor effects of ketorolac. PMID- 2590611 TI - Differential effect of aspirin on thromboxane and prostaglandin biosynthesis in man. AB - 1. Effects of a single intravenous dose of aspirin (600 mg) on bradykinin stimulated prostaglandin (PG) and on thromboxane (TX) biosynthesis were determined in nine healthy male volunteers. Plasma concentrations of 6-oxo-PGF1 alpha and 13,14-dihydro-15-oxo-PGF2 alpha were measured in samples obtained during repeated 10 min intravenous infusions of bradykinin before and up to 6 h after the dose of aspirin. TXB2 was measured in serum from blood allowed to clot at 37 degrees C. 2. Aspirin inhibited bradykinin stimulated PG and platelet TX biosynthesis 0.5 h after the dose. Serum TXB2 remained low, whereas PG synthesis recovered within 6 h. 3. Effects of intravenous sodium salicylate (600 mg) were studied identically in eight subjects. Prostanoid biosynthesis was not inhibited. 4. Biosynthesis of prostacyclin and TXA2 under basal conditions was studied in eight subjects by measuring 2,3-dinor-6-oxo-PGF1 alpha and 2,3-dinor-TXB2 in hourly urine samples obtained during and after intravenous infusion of aspirin and, on a separate occasion, of vehicle. 5. Aspirin infusion reduced urinary excretion of both metabolites greater than 90%, but excretion of 2,3-dinor-6-oxo PGF1 alpha recovered more rapidly than did that of 2,3-dinor-TXB2. 6. We conclude that cyclo-oxygenase is rapidly synthesised in bradykinin-responsive tissues in vivo and that this reflects similarly rapid enzyme biosynthesis in tissues that produce PGI2 under basal conditions. PMID- 2590612 TI - Enhanced gastric mucosal bleeding with doses of aspirin used for prophylaxis and its reduction by ranitidine. AB - 1. We evaluated injury to the human gastric mucosa caused by low doses of aspirin and its prophylaxis by ranitidine. On two separate occasions, 30 subjects took aspirin 300 mg daily for 12 days either with or without ranitidine 150 mg, 30 min before aspirin. This dose of aspirin caused more than a 5 fold increase in gastric bleeding, from control values of 0.5 microliters 10 min-1 (95% confidence limits 0.3-0.8 microliters 10 min-1) to 2.8 microliters 10 min-1 (1.9-4.1 microliters 10 min-1, P less than 0.01) after 5 days of aspirin. Adaptation did not occur and the gastric bleeding rates remained elevated at 3.4 microliters 10 min-1 (1.9-6.1 microliters 10 min-1) after 12 days of aspirin consumption (P less than 0.01). 2. Coadministration of ranitidine significantly raised intragastric pH and reduced aspirin induced bleeding to 1.5 microliters 10 min-1 (1.0-2.3 microliters 10 min-1) after 5 days and 1.6 (1.0-2.5 microliters 10 min-1) after 12 days (P less than 0.05). 3. Although these values were higher than control levels our results raise the possibility that coadministration of ranitidine may reduce the incidence of peptic ulceration and gastrointestinal haemorrhage which is increasingly reported in some subjects taking low dose aspirin for vascular prophylaxis. PMID- 2590613 TI - Factors affecting free (unbound) lignocaine concentration in suspected acute myocardial infarction. AB - 1. Free plasma lignocaine concentrations were measured for up to 48 h after constant infusion of the drug in 41 subjects with suspected acute myocardial infarction. 2. The free plasma lignocaine clearance at 12 h was significantly and proportionately related to body weight and to the presence of mild (Killip Class II) heart failure, with an 18% reduction in free clearance in the latter condition. 3. The free plasma lignocaine was not related to sex, age or the presence of confirmed acute myocardial infarction, when corrected for the effects of body weight and presence of heart failure. 4. Free plasma lignocaine concentration 1 h after a fixed loading dose were also significantly related to body weight and presence of heart failure but not to sex, age or proven acute myocardial infarction. 5. The data indicate that correction of loading and maintenance infusion for body weight and presence of (even mild) heart failure should somewhat reduce variability in free (and presumably active) plasma lignocaine concentrations but that the free plasma lignocaine concentration at 12 h is most accurately predicted by measuring the free (and to a lesser extent total) plasma lignocaine concentration at 1 h. PMID- 2590614 TI - Morphine metabolism in children. AB - 1. The metabolism of morphine was studied in 12 children and nine premature neonates on a continuous infusion of morphine (10-360 micrograms kg-1 h-1). 2. The mean plasma clearance of morphine was significantly higher in children than neonates (25.7 and 4.7 ml min-1 kg-1, respectively) (P less than 0.01). 3. All the neonates and children had detectable concentrations of morphine-3-glucuronide (M3G) in plasma. All the children and five neonates had detectable concentrations of morphine-6-glucuronide (M6G) in plasma or urine. 4. The M3G/morphine ratios in plasma and urine, and M6G/morphine ratios in urine were significantly higher in children than neonates (P less than 0.01), suggesting that morphine glucuronidation capacity is enhanced after the neonatal period. 5. There was no difference in the M3G/M6G ratio in children and neonates, indicating a parallel development of both glucuronidation pathways. PMID- 2590615 TI - The influence of food on the pharmacokinetics of 'biphasic' nifedipine at steady state in normal subjects. AB - Previous studies following single dose administration have suggested that the pharmacokinetics of various nifedipine formulations could be influenced by the timing of associated food consumption. In order more closely to reflect the clinical situation we have carried out a study at steady state using a 'biphasic' formulation comprising 'rapid' and 'retarded' drug release components. Fifteen normal subjects took 20 mg 'biphasic' nifedipine 12 hourly for 10 days. Studies were carried out on days 4, 7 and 10. On these days the nifedipine was taken 2 h or 1 h before or immediately following a light breakfast. A light breakfast influenced neither the rate nor the extent of nifedipine absorption nor the rate or extent of major metabolite appearance. We conclude that at steady state the timing of a light meal is unlikely to alter in any clinically important manner the pharmacokinetics of nifedipine released from 'biphasic' tablets. PMID- 2590616 TI - Bioavailability of intranasal metoclopramide. AB - After intranasal administration of metoclopramide, (5 mg in 0.5 ml sterile water) the maximum plasma concentration of 13.5 +/- 7.3 (mean +/- s.d.) ng ml-1 was achieved. Absolute bioavailability was 50.5 +/- 29.5%, 110 +/- 41 min later. We conclude that the intranasal route does not allow rapid absorption of the drug and is not associated with greater bioavailability than the oral route. PMID- 2590618 TI - Appendicectomy at cholecystectomy--an appraisal. AB - The effect of incidental appendicectomy in patients undergoing elective biliary surgery has been studied prospectively in 430 patients. In 236 patients the appendix was removed at the time of biliary surgery; in 194 patients the appendix was not removed or had already been removed at a previous operation. There was no significant difference between the two groups with regard to the incidence of septic complications--especially wound infection--more general complications, or in the mean post-operative stay in hospital. Histological examination of the macroscopically normal appendices revealed a surprising incidence of pathology (greater than 50 per cent). Provided the patient receives routine antibiotic prophylaxis, there appears to be a case for removing the appendix at the time of cholecystectomy if it is readily accessible. PMID- 2590617 TI - The value of therapeutic drug monitoring to the practising physician--an hypothesis needing sensible application. PMID- 2590620 TI - If I had familial hypercholesterolaemia. PMID- 2590619 TI - Low concentration dithranol and coal tar (Psorin) in psoriasis: a comparison with alcoholic coal tar extract and allantoin (Alphosyl). AB - Psoriasis is difficult to manage in general practice, mainly because the standard treatments produce side effects, or are ineffective in both the short and long term. In recent years, the main topical therapies have included extracts of coal tar or dithranol. In a six-week within-patient trial, 23 patients applied two different treatments to the left and right halves of their bodies. A new preparation (Psorin, Thames Laboratories), containing relatively low concentrations of dithranol and crude coal tar, was significantly more effective and more acceptable than a refined alcoholic extract of coal tar with allantoin (Alphosyl, Stafford Miller Ltd). PMID- 2590621 TI - Three cases of gangrenous ischaemic colitis. AB - The concept of ischaemic colitis is relatively recent. It is more common in the elderly than is realised, and results from reduction or occlusion of the blood supply to the colon. Three cases of ischaemic colitis in its gangrenous form are reported. The patients died despite all therapeutic measures. Necropsy revealed full thickness gangrene of the involved segment of the colon. PMID- 2590623 TI - Organising clinical research: 4. Getting the work done. PMID- 2590622 TI - Organising clinical research: 1. Before you start. PMID- 2590624 TI - Comparative study of Riflux Forte and Riflux in cases of reflux oesophagitis. AB - In an open, randomised, comparative study of 68 endoscopically proven cases of reflux oesophagitis, one antacid with relatively high acid-neutralising capacity (Riflux Forte) and another with lower acid-neutralising capacity (Riflux) were compared. Except for a relatively higher number of cases of severe oesophagitis in the Riflux Forte group (31 vs 19), the patient populations were homogeneous. A consistent trend of rapid and increased diminution in severity of symptoms was seen with both Riflux and Riflux Forte. Although differences between the two groups were not statistically significant, the trend towards a better response was reflected in symptomatic improvement (score difference 14.2 vs 12.0 between one and eight weeks), percentage improvement (93.0 vs 83.7), global assessment (2.9 vs 2.7) and oesophagitis grading on endoscopic assessment (2.5 vs 1.9). These data indicate that, while Riflux and Riflux Forte will produce equivalent results in cases of mild to moderate reflux oesophagitis, the additional acid neutralising capacity of Riflux Forte provides it with the potential to be more useful in severe cases. PMID- 2590625 TI - Effectiveness of a new coal tar preparation in the treatment of chronic plaque type psoriasis. AB - In a contralateral study a new coal tar gel was compared with a topical corticosteroid in the treatment of psoriasis. In 45 patients treated for four weeks, the coal tar gel proved significantly more effective. PMID- 2590626 TI - Comparison of qid and bd administration of De-Nol in the short term treatment of duodenal ulcer. AB - One hundred and twelve patients (80 males, 32 females) with endoscopically proven gastroduodenal ulcer participated in a clinical trial to compare the ulcer healing effect of colloidal bismuth subcitrate (CBS) at standard dosage, administered either twice daily (Group A) or four times a day (Group B). Endoscopic control was programmed at Week 4 and Week 8, in case of delayed healing. With an 'intention to treat' analysis, the healing percentage at four weeks was 69.6 for Group A and 82.1 for Group B (IC95 of percentage difference: 0.049 to 2.29). At Week 8, the healing percentage for Groups A and B was 87.5 and 94.6 per cent respectively (IC95: -0.05 to 0.19). The mean steady-state values of bismuth levels in plasma were well below the threshold value of 50 micrograms/l. The data confirm the efficacy and acceptability of CBS swallowing formulation tablets and suggest that administration twice daily is an acceptable alternative to the qid schedule. PMID- 2590627 TI - Therapeutic focus. Patient compliance in gynaecology. PMID- 2590628 TI - A study of public knowledge of AIDS among Asian people in Bradford. PMID- 2590629 TI - Normotension, ventricular tachycardia and palpitation: an unusual presentation of phaeochromocytoma. AB - Phaeochromocytomas are rare catecholamine-producing tumours arising from the cells of the sympathetic nervous system. They account for less than one per cent of hypertension. Undiagnosed sufferers are usually hypertensive and experience episodes of hypertensive crisis. Patients presenting with hypertensive attacks only at intervals and who are at other times normotensive account for only one to five per cent of cases. These subjects have been found to predominantly secrete adrenaline from their tumours. We report here such a case in a 43-year-old man who initially presented to the Coronary Care Unit. PMID- 2590630 TI - Prepatellar bursitis associated with asthma. AB - A child who developed prepatellar bursitis during an asthmatic attack is described. Asthmatic attacks should be considered as one of the possible causes of bursitis. PMID- 2590631 TI - Perforated jejunal diverticulitis. AB - Perforated jejunal diverticulitis is very rare. We describe two cases seen in one surgical unit in a four month period. The problems in early diagnosis are discussed and the need for prompt surgical intervention emphasised if mortality is to be reduced. PMID- 2590632 TI - Does communication between investigators improve the conduct of the multicentre study? AB - Meetings between investigators participating in multicentre clinical trials are rarely held. Evidence is presented from a computerised system of multicentre trial management that there are advantages to both physicians and companies in improving communication and holding regular meetings. PMID- 2590633 TI - The role of the research nurse in clinical trials. PMID- 2590634 TI - Factors influencing the initial decision to use an intrauterine device. AB - This study analyses data from 104 women who elected to use an IUD for the first time. The reason they gave for requesting the IUD was evaluated against a number of personal and psychological characteristics. Parous women who had recently given birth were more likely to choose an IUD because of a fear of non-compliance with oral contraceptives and possible problems with other methods, eg, hormone injections. Nulliparous women, and women who had not recently given birth were much more likely to choose the IUD as their method of contraception because they felt it had health advantages and/or was more convenient than other methods. These reasons for choosing an IUD are not usually given a high priority by contraceptive methodology providers. PMID- 2590635 TI - Primary hyperthyroidism occurring in association with acromegaly. AB - Two patients with acromegaly who also developed primary hyperthyroidism are described. One case presented de novo with Graves' disease and acromegaly and the other developed hyperthyroidism several years after the diagnosis of acromegaly had been made. No associated adenomas could be demonstrated. The association between acromegaly and thyroid disease is discussed. PMID- 2590636 TI - Hypoglycorrhagia does not necessarily indicate infection. AB - A case is reported illustrating two points: 1. haemorrhage can occur in cerebral infarct even without the use of anticoagulants; 2. this haemorrhage can extend into the subarachnoid space, causing chemical meningitis, and may produce moderately severe low CSF sugar. The importance of this point is emphasised when faced with a stroke patient who develops fever. PMID- 2590637 TI - The knotted nasogastric tube: a simple solution. PMID- 2590638 TI - Amiodarone overdose and its management. AB - A patient taking an overdose of 3.4 g of amiodarone is described. Consciousness and physical examination remained normal throughout. Continuous electrocardiographic monitoring for 48 hours after admission revealed only a self limiting episode of ventricular tachycardia, despite high serum levels of the drug (serum desethylamiodarone levels 4.4 mg/l). The pharmacokinetic properties of amiodarone and treatment strategies for the overdose situation are discussed. It is suggested that there may be a role for the use of cholestyramine in the treatment of both acute and chronic amiodarone toxicity. PMID- 2590639 TI - COSHH and the NHS. PMID- 2590640 TI - Pulmonary function among pulp and paper workers in Berlin, New Hampshire. AB - Pulmonary function was studied among pulp and paper workers from a production facility in New Hampshire. Subjects were first tested in the 1960s and then surveyed at regular intervals up to 1985. The current study examined results for the 339 subjects who participated in at least one of the two most recent follow up surveys in 1979 and 1985. For the 171 subjects who were tested in both surveys, the pulmonary function values were higher and the effect of pulp mill work was diminished compared with the findings for the 168 subjects who were tested in just one of the two surveys. To avoid the loss of less healthy subjects and the subsequent bias in effect estimate, the 1985 data were analysed cross sectionally with the inclusion of data from 1979 for those subjects who had not been followed up in the last survey. The subjects with work experience in the pulp mill had mean levels of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) lower than those of unexposed subjects who had never worked in the pulp or paper production areas. Based on parameter estimates from regression analysis, each year of employment in the pulp operation was associated with a -5.8 ml change in FEV1 (p = 0.08) and a -7.2 ml change in FVC (p = 0.04). Ninety one per cent of the subjects with pulp mill experience had terminated employment in that area of the company, so the association with decreased lung function appears to be a non-reversible effect that persisted after the cessation of exposure. PMID- 2590643 TI - Prevalence of byssinosis in textile mills at Ahmedabad, India. AB - In an epidemiological study carried out in three textile mills at Ahmedabad, India, 929 workers were examined from the spinning departments. The mean prevalence of byssinosis in the blow section was 29.62%, whereas in the card section it was 37.83%. The concentrations of cotton dust (dust less fly) were high in the blow and card sections (4.00 mg/m3 in the blow and 3.06 mg/m3 in the card section). This study suggests that the prevalence of byssinosis is not low in the textile mills of India as reported in many earlier Indian studies. PMID- 2590642 TI - Role of computed tomography in evaluating asbestos related lung disease. AB - To find how computed tomography (CT) may be effectively used in individuals with suspected asbestos related lung disease 30 men with a history of exposure to asbestos were studied. All subjects underwent high kilovoltage posteroanterior and left lateral chest radiographs and chest CT. Eighteen were randomly selected asbestos workers referred for routine surveillance. The remaining 12 were patients who had been referred for investigation of respiratory symptoms or abnormal routine chest radiograph, or both, and found to have chest radiographic changes compatible with asbestos related lung disease. In the group referred for routine surveillance both pleural shadowing and pulmonary shadowing were shown on CT but not chest radiographs in only one case. Five were thought to have pleural shadowing on chest radiographs but this was confirmed on CT in only one case. All 12 patients referred for investigation showed pleural shadowing on chest radiographs; this was confirmed in all cases on CT which also showed unsuspected pulmonary shadowing in five cases. These findings suggest that it is not appropriate to use chest CT routinely in all asbestos workers referred for routine surveillance. When CT is used selectively in those with pleural shadowing on plain chest radiography, however, it is helpful in refuting or confirming the presence of pleural disease and may show unsuspected pulmonary shadowing. PMID- 2590641 TI - Differences in lung function and prevalence of pneumoconiosis between two kaolin plants. AB - To investigate the origin of differences in previously published pulmonary function studies of workers in kaolin plants in Georgia, spirometric and radiographic data collected in a cross sectional survey of two large plants were analysed. As compared with workers in plant 2, workers in plant 1 had a 2.7-fold greater prevalence of pneumoconiosis and a mean 0.361 decrement in adjusted forced vital capacity. Our previous finding that exposure to kaolin was not associated with a decrement in lung function may have resulted from failure to consider differences between the plants. PMID- 2590644 TI - A cytogenetic and haematological investigation of oil exposed workers in a Norwegian cable manufacturing company. AB - Cytogenetic and haematological parameters were studied in 31 oil exposed workers and 31 office workers matched for age and smoking, all men employed by a Norwegian cable manufacturing company. Information was obtained about tobacco and alcohol consumption, infections, allergies, chronic diseases, use of medicines, and exposure to radiography. A decrease in the absolute lymphocyte counts was observed in the most heavily exposed subgroup (p less than 0.05) but no other significant differences were found between exposed workers and referents. The influence of non-occupational variables on the cytogenetic parameters was studied by stepwise multiple linear regression analysis. The frequency of sister chromatid exchanges appeared to be influenced by smoking history (p less than 0.05) and season of sampling (p less than 0.01) and, if season was excluded, by age (p less than 0.05) and current smoking (p less than 0.05). The number of cells with chromosomal aberrations increased with age (p less than 0.05) and lymphocyte count (p less than 0.05), whereas the frequency of stable rearrangements was negatively correlated with current smoking (p less than 0.01). PMID- 2590645 TI - Clinical and neurobehavioural study of the acute and chronic neurotoxicity of styrene. AB - A cross sectional field study of workers exposed to styrene was performed to evaluate possible acute and chronic neurotoxic effects. A total of 36 workers of four companies handling polyester resin materials for one to 16 years (median: 7 years) and two control groups were each examined on a Monday. The control group 1 (formed to compare acute effects) consisted of 20 men from two companies with no exposure to neurotoxic chemicals. To compare chronic effects, a second control group was formed by "one to one matching" with respect to age, socioeconomic status, and pre-exposure intelligence level. Ambient air monitoring using active sampling (short time) and passive samplers (long time) showed styrene in air concentrations as follows: range 3-251 ppm (median: 18 ppm) and concentrations 140-600 ppm during lamination of the inside of boats. For biological monitoring the results were as follows (postshift samples: range/median): styrene in blood: 5-482 micrograms/dl (39 micrograms/dl), mandelic acid urine: 0.01-3.64 g/l (0.21 g/l), and phenylglyoxylic acid urine: 0.01-0.87 g/l (0.19 g/l). The clinical examination found no signs or symptoms of peripheral neuropathy or encephalopathy. The principal work related health complaints were acute, reversible irritation of the eyes that occurred after exposure to styrene concentrations of 200 ppm or more. The neurobehavioural tests showed no significant differences in acute effects (p greater than 0.05) between the two groups or between preshift and postshift testing. Nor were there any significant differences in the relevant neurobehavioural variables between the styrene workers and the controls. It is concluded that occupational exposure to styrene concentrations in air up to 100 ppm causes no adverse acute or chronic effects on the central nervous system. PMID- 2590646 TI - Neuropsychiatric effects of low exposure to styrene. AB - Workers exposed to styrene concentrations of about 50 mg/m3 at a plant manufacturing reinforced polyester boats were examined for neuropsychiatric symptoms both in close connection with exposure and also seven months after exposure had ceased. Physical workload is important for the uptake of styrene and was about 50 W at this plant. On the first occasion, after one week with no exposure, the workers reported a high frequency of neuropsychiatric symptoms such as fatigue, irritation, and forgetfulness whereas seven months later the frequency of these symptoms was low. These observations indicate that exposure to styrene at about 50 mg/m3 may induce reversible neuraesthenic symptoms. Even the relatively low Swedish standard (110 mg/m3 = 25 ppm) may, therefore, need revising. PMID- 2590647 TI - Risk of cancer in pesticide applicators in Swedish agriculture. AB - The risk of cancer was analysed in a cohort of 20,245 licensed pesticide applicators in agriculture who had licences issued between 1965 and 1976. Most were men (99%) and about 50% had been born in 1935 or later. The cohort was followed up in the Swedish Cancer Register from date of licence until death or 31 December 1982. The mean follow up time was 12.2 years. Average time since first exposure was longer, however, since one fifth of the cohort was exposed in the 1950s. A total of 558 malignant tumours was found compared with 649.8 expected, which resulted in a statistically significantly decreased standardised incidence ratio (SIR) of 0.86 (95% confidence interval (CI): 0.79-0.93). Significantly decreased risks of cancer were also found for liver (SIR = 0.45, 95% CI: 0.18 0.93), pancreas (SIR = 0.50, 95% CI: 0.26-0.87), lung (SIR = 0.50, 95% CI: 0.35 0.68), and kidney (SIR = 0.53, 95% CI: 0.32-0.84). No statistically significantly increased risks or any time trends were observed. SIR for testicular cancer was increased (SIR = 1.55, 95% CI: 0.92-2.45) and increased with period since licence. Eighteen cases with testicular cancer were found. For those born in 1935 or later a non-significant increased overall risk of cancer was observed (SIR = 1.07, 95% CI: 0.82-1.37). Comparisons were made with agricultural workers in general since pesticide applicators are mainly farmers that use or have used pesticides to a greater extent. Higher risks for pesticide applicators were found for testicular cancer, tumours of the nervous system and endocrine glands, and Hodgkin's disease. PMID- 2590648 TI - Relation between renal function tests and a retrospective organic solvent exposure score. AB - In case-control studies on glomerulonephritis and organic solvents several authors have assessed exposure to organic solvents with a score based on the self reported occupational history. The underlying principle is that all exposures can be weighted by an intensity factor and then added to get one number representative of lifetime exposure. As this score has hitherto not been validated the relation between this exposure score and kidney function tests in a population of workers with past or present exposure to organic solvents was examined. The results suggest that such relations do exist for the N-acetyl-beta D-glucosaminidase (NAG) activity, erythrocyturia, and, perhaps, albuminuria but not for the protein creatinine ratio or for leucocyturia. PMID- 2590649 TI - Occupational asthma due to unheated polyvinylchloride resin dust. AB - Polyvinylchloride (PVC) resins are widely used in industry. Asthma due to the thermal degradation products of PVC are well documented. In this first case of occupational asthma due to unheated PVC resin dust the patient was exposed to PVC resin dust during the mixing of chemicals used for making plastic seals for bottle caps. PMID- 2590650 TI - Intrauterine growth retardation: let's be clear about it. PMID- 2590651 TI - Prostaglandin E production by the fetal membranes in unexplained preterm labour and preterm labour associated with chorioamnionitis. AB - The production of prostaglandin E (PGE) by amnion, choriodecidua and placenta was measured in 45 women delivered after spontaneous preterm labour, in 10 women delivered electively preterm, in 30 women at elective caesarean section at term, and in 28 women after spontaneous labour at term. In the preterm labour group 24 women had normal placental histology, and gestational age was 34 (31-36) weeks (median and range); 18 women had evidence of chorioamnionitis and gestational age was significantly shorter, 30 (24-36) weeks; three other patients had placental abruption. In the absence of inflammatory infiltration of these tissues the highest PGE output (fmol/mg dry weight/2 h) was found after labour at term and the lowest after uncomplicated preterm labour: 2640 (360-15,580) (median and range) compared with 1414 (164-11,045) in amnion, 677 (100-3245) compared with 308 (39-1086) in choriodecidua, and 1200 (520-3022) compared with 578 (150-1859) in placenta, respectively. Tissues showing chorioamnionitis produced much higher outputs of PGE from amnion (12,278, 1799-82,617) and from choriodecidua (1018, 216-11,768), but not from placenta (616, 89-4131). Chorioamnionitis seems to cause very early preterm labour by increasing PG production in the amnion and choriodecidua. PMID- 2590652 TI - Changes in fetal monitoring practice in the UK: 1977-1984. AB - A postal survey was undertaken between 1985 and 1987 to assess the changes that have taken place in fetal monitoring practice since 1977. Replies were received from 253 (92%) of 276 consultant obstetric units canvassed. Biophysical methods of assessing fetal well-being in the antepartum period are almost universally employed and are accepted as the best discriminators of the need to deliver the pregnancy. The number of fetal heart rate monitors on labour wards has increased by 88%. Overall, 63% of units monitor more than 60% of their patients in labour, and 87% permit suitably trained midwives to apply fetal scalp electrodes, which must now be regarded as standard practice. There is still a need for a simplified technique for fetal blood sampling. The perinatal mortality rate correlates with a prematurity factor and probably bears a greater relation to the population served than to the degree of monitoring provided. PMID- 2590654 TI - A study of the experience of Glasgow women in the climacteric years. AB - Overall, 424 women between 40 and 60 years of age were interviewed with reference to their experience of the menopause; 179 (42%) expressed a 'need for treatment' which was more marked in those who had had a hysterectomy (57%) or oophorectomy (76%). Of those who sought help (174) a large majority (92%) had seen their general practitioner and 72% received some form of drug therapy, predominantly hormone replacement therapy (HRT) or psychotropic drugs. Twenty-eight women were currently having HRT (7%) and 39 (9%) had previously had HRT. Only 12 women (3%) had received greater than 3 years of HRT and nine of these had had an oophorectomy. Only 1% of other women were 'long-term' users of HRT. Of the 424 women 11% expressed dissatisfaction with their general practitioner's approach to this subject. PMID- 2590653 TI - Outcome of pregnancies complicated by severe hypertension and delivered before 34 weeks; stepwise logistic regression analysis of prognostic factors. AB - The outcome is described for 106 patients with severe hypertension in pregnancy requiring delivery between 26 and 34 weeks. Management was with methyldopa, hydralazine when required and delivery by caesarean section when indicated. Most patients were delivered for cardiotocographic fetal distress or unstable maternal blood pressure. Eighty-five babies (80%) survived and were well at follow-up at 1 year; the perinatal mortality was 123/1000 total births. One patient had postpartum eclampsia, one had pulmonary oedema and one had transient renal failure, but all mothers left hospital well. Stepwise logistic regression analysis showed that the primary positive factor for survival of a healthy baby was gestational age, which was strongly correlated with birthweight. The need for caesarean section as an emergency, hypotension after parenteral hydralazine, intrauterine growth retardation, and severe proteinuria were adverse factors. Intraventricular haemorrhage had a major adverse effect on neonatal survival; it was predisposed to by prolonged maternal hypertension and by low gestational age. PMID- 2590655 TI - Changes in the connective tissue of corpus and cervix uteri during ripening and labour in term pregnancy. AB - The composition of the connective tissue of human cervix and corpus uteri was studied in tissue specimens from seven nonpregnant women and 14 pregnant women, delivered at term by section, to examine spontaneous cervical ripening and labour induced changes in both the uterine and the cervical connective tissue. The main finding in both the cervix and the corpus was a large (40-60%) decrease of the collagen concentration. The collagen extractability, obtained by pepsin digestion, was increased twofold, suggesting a change of the organization of the collagen fibrils. This reorganization process could also be demonstrated by a large increase of the collagenolytic activity demonstrated with an artificial DNP peptide substrate. The concentrations of sulphated glycosaminoglycans was lower in pregnant women than in non-pregnant women. The results show that both the cervix and the corpus uteri contain substantial amounts of connective tissue components (collagen, sulphated glycosaminoglycans and hyaluronic acid) and that during ripening, reconstruction of the connective tissue components occurs in both sites. This indicates that the cervical state reflects that of the myometrium. PMID- 2590656 TI - Ethnic influence on uterine activity in spontaneous normal labour. AB - Uterine activity in spontaneous normal labour was studied in Singaporean Malay women at term with a singleton vertex presentation. Nulliparae had significantly higher uterine activity compared with their multiparous counterparts. Uterine activity in the Malay population was compared with that of a similar Chinese population. When controlled for parity, maternal height and birthweight of babies, there was no difference in uterine activity between the two groups. PMID- 2590658 TI - Direct chromosome analysis in the second and third trimesters by placental biopsy in 30 pregnancies. AB - Direct chromosome analysis was performed on placental villi obtained by ultrasound-guided transabdominal needle aspiration in 30 women at between 23 and 37 weeks gestation. Placental biopsy is simple in the presence of severe oligohydramnios where fetal blood sampling is usually more difficult. Direct karyotyping of placental villi is more rapid than chromosomal analysis from fetal blood and from amniotic fluid. Two chromosomal anomalies were discovered: one trisomy 18 and one 6p+. Villus sampling failed in one woman and two samples obtained at 36 and 37 weeks gestation could not be karyotyped. The procedure did not affect the outcome of the pregnancy. PMID- 2590657 TI - Some endocrinological events associated with early pregnancy failure. AB - Serial measurements of serum progesterone, oestradiol, human chorionic gonadotrophin (hCG) and human placental lactogen (hPL) have been determined in 33 women experiencing early pregnancy failure and compared with the values of the same hormones in 72 healthy women having uncomplicated pregnancies. Steroid production by the corpus luteum seemed similar in both groups up to 6 weeks gestation but thereafter placental steroidogenesis was not evident in those women in whom spontaneous pregnancy losses occurred. Placental production of the two protein hormones, hCG and hPL, did take place, and whereas the circulating levels were not as high as in normal pregnancies, levels did usually increase before clinical evidence of miscarriage occurred. hCG was not a sensitive discriminator of subsequent failure. In these women there were no significant hormone differences between those with evidence of a fetus and those without. PMID- 2590659 TI - Epidemiology and trends in hospital discharges for pelvic inflammatory disease in England, 1975 to 1985. AB - Hospital Inpatient Enquiry data were analysed to determine trends in hospital discharges for pelvic inflammatory disease in England from 1975 to 1985. Cases where the disease was thought to be related to another condition, e.g. appendicitis, were excluded from the analysis. Discharge rates for both acute and chronic disease increased over the review period and there was a 28% increase in the discharge rate for total disease. Women in their 20s were most likely to be involved and this group showed the greatest increase in the discharge rate, both for acute and chronic disease. In the 20-24-year age group the rate of discharge for acute disease rose by 50%, from 125.6/100,000 in 1975 to 189.0/100,000 in 1985. Patients with a diagnosis of chronic pelvic inflammatory disease tended to be older than those with acute disease. Women who were divorced were more at risk of both acute and chronic forms of the disease than single or married women. Increase in the use of surgery to confirm the diagnosis occurred only for those with chronic disease. About a quarter of patients with acute disease had the diagnosis confirmed surgically, and this proportion did not change in the period studied, although laparoscopy increased as laparotomy decreased. PMID- 2590660 TI - Thrombocythaemia and recurrent miscarriage. PMID- 2590661 TI - Outcome of labour in occipitoposterior positions in an African population. PMID- 2590662 TI - Plasma lipid risk factors in oophorectomized women. PMID- 2590663 TI - Hydatidiform mole following in-vitro fertilization. Case report. PMID- 2590664 TI - Abstracts of papers presented at the meeting of the Blair Bell Research Society. 25 April 1989, London. PMID- 2590665 TI - Haemodynamic changes in gestational proteinuric hypertension: the effects of rapid volume expansion and vasodilator therapy. PMID- 2590666 TI - Diagnostic role of dilatation and curettage in the management of abnormal premenopausal bleeding. PMID- 2590667 TI - Commentary. Human immunodeficiency virus infection in women. PMID- 2590668 TI - Minimal/mild endometriosis and infertility. PMID- 2590669 TI - Serum CA 125 in acute pelvic inflammatory disease. PMID- 2590670 TI - Differential labeling of the erythrocyte hexose carrier by N-ethylmaleimide: correlation of transport inhibition with reactive carrier sulfhydryl groups. AB - Inhibition of hexose transport by N-ethylmaleimide was studied with regard to alkylation of different types of sulfhydryl group on the hexose carrier of the human erythrocyte. Uptake of 3-O-methylglucose was progressively and irreversibly inhibited by N-ethylmaleimide, with a half-maximal effect at 10-13 mM. A sulfhydryl group known to exist on the exofacial carrier was not involved in transport inhibition by N-ethylmaleimide, since reversible protection of this group by the impermeant sulfhydryl reagent 5,5'-dithiobis(2-nitrobenzoic acid) had no effect on the ability of N-ethylmaleimide to inhibit transport, or on its ability to decrease the affinity of the exofacial carrier for maltose. Nevertheless, the exofacial sulfhydryl was quite reactive with N-ethylmaleimide, since it was possible using a differential labeling technique to specifically label this group in protein-depleted ghosts with a half-maximal effect at 0.3 mM N-[3H]ethylmaleimide, and to localize it to the Mr 19,000 tryptic carrier fragment. Transport inhibition by N-ethylmaleimide correlated best with labeling of a single cytochalasin B-sensitive internal sulfhydryl group on the glycosylated Mr 23,000-40,000 tryptic fragment of the carrier, which was half maximally labeled at about 4 mM reagent. Whereas N-ethylmaleimide readily alkylates the exofacial carrier sulfhydryl, it inhibits transport by reacting with at least one internal carrier sulfhydryl located on the glycosylated tryptic carrier fragment. PMID- 2590671 TI - Cross-linking of phosphatidylethanolamine neighbors with dimethylsuberimidate is sensitive to the lipid phase. AB - Dimethylsuberimidate was reacted with aqueous dispersions of dipalmitoylphosphatidylethanolamine, dimyristoylphosphatidylethanolamine, dilauroylphosphatidylethanolamine, and dielaidoylphosphatidylethanolamine at pH 10 and at pH 8. The amount of amidine dimer formation was about four times greater above the gel-to-fluid phase transition of each lipid than below the transition. The transition temperature of each phosphatidylethanolamine, measured by steady-state fluorescence anisotropy of cis-parinaric acid, was lower at pH 10 than at pH 8 or in water. The ability of dimethylsuberimidate to discriminate between phosphatidylethanolamines in the fluid and gel phases should allow use of this reagent to identify phosphatidylethanolamine species within the gel or fluid lipid phase. PMID- 2590672 TI - Miscibility of octyl glucoside-phosphatidylcholine micellar solutions. Partition of the nicotinic acetylcholine receptor into the surfactant-rich phase. AB - Phospholipid phosphatidylcholines (PC) and the nonionic detergent octyl glucoside (OG) were found to form a miscibility gap in aqueous solution at a molar ratio [OC]T/[PC]T=2.6-2.4. This ratio is just below the critical ratio for the formation of vesicles. At [PC] greater than 1.3 g/l the transition from micelles to vesicles is not direct but via a surfactant-rich phase (SRP). The various stability regions are summarized in a phase diagram. Though the partition coefficient gamma=[Db]/[Dw] increases markedly with temperature, the critical ratio for the phase separation R(c) is biased to higher detergent concentrations. This behaviour can be explained by increased motion of the hydrocarbon moiety at higher temperatures. The different phases are investigated by light microscopy, nuclear magnetic resonance and thin-layer chromatography. The miscibility gap of PC/OG is compared to the lamellar phase of Triton X-114; the miscibility gap has implications for membrane protein reconstitution and can be used for membrane protein purification. The Torpedo californica nicotinic acetylcholine receptor (n AcChR) was found to partition into the SRP. PMID- 2590673 TI - Nonelectrolyte permeability of liposomes of hydroxyfatty acid-containing phosphatidylcholines. AB - Two phosphatidylcholines containing hydroxylated fatty acids, 1-palmitoyl-2-[5 hydroxy-6,8,11,14-eicosatetraenoyl]-sn-glycero-3- phosphocholine (1-palm-2-5HETE PC) and 1-palmitoyl-2-[15(S)-hydroxy-5,8,11,13- eicosatetraenoyl]-sn-glycero-3 phosphocholine (1-palm-2-15HETE PC), and one phosphatidylcholine containing nonhydroxylated fatty acids, 1-palmitoyl-2-arachidonyl-sn-glycero-3 phosphocholine (1-palm-2-arach PC) were synthesized. Permeation of small nonelectrolytes (glycerol, 1,2-propanediol, urea, methylurea, propionamide and dimethylformamide) was assessed in multilamellar liposomes containing these synthetic PCs plus egg yolk phosphatidycholine (EPC) in the presence and absence of cholesterol. In liposomes containing 23% cholesterol, 69.3% EPC and 7.7% of either 1-palm-2-5HETE PC or 1-palm-2-15HETE PC the permeability to small nonelectrolytes was 60 to 400% greater than in liposomes containing 23% cholesterol and 77% EPC. The HETE-containing PCs also increased permeability in liposomes without cholesterol but the effects were less striking. Addition of the synthetic PCs did not affect the energy of activation of permeation. PMID- 2590674 TI - Translocation of oleic acid across the erythrocyte membrane. Evidence for a fast process. AB - To clarify divergent views concerning the mechanism of fatty acid translocation across biomembranes this issue was now investigated in human erythrocytes. Translocation rates of exogenously inserted radioactive oleic acid across the membrane of native cells were derived from the time-dependent increase of the fraction of radioactivity becoming non-extractable by albumin. No accumulation of non-extractable unesterified oleic acid occurred. The rate of transfer was markedly suppressed by SH-reagents and by ATP-depletion. The suppression, however, resulted from a mere decrease of incorporation of oleic acid into phospholipids and was not accompanied by an increase of non-extractable unesterified oleic acid. These findings were reconcilable with the concept of a slow, possibly carrier-mediated fatty acid transfer as well as a very fast presumably, diffusional process not resolvable by the albumin extraction procedure. This ambiguity was resolved by using resealed ghosts, which are unable to incorporate oleic acid into phospholipids. In such ghosts all of the oleic acid inserted into the membrane remains extractable by albumin even after prolonged incubation. On the other hand, ghosts containing albumin accumulated non-extractable oleic acid. The rate of accumulation was beyond the time resolution of the albumin extraction procedure at 4 degrees C. Oleic acid uptake into albumin-containing ghosts became kinetically resolvable when the fatty acid was added as a complex with albumin. Correspondingly, time-resolvable release of oleic acid, originally complexed to internal albumin, into an albumin-containing medium was demonstrated at 4 degrees C. Rate and extent of these redistributions of oleic acid were dependent on the concentrations of internal and external albumin. This indicates limitation by the dissociation of oleic acid from albumin and not its translocation across the membrane. Translocation of oleic acid, which is probably a simple diffusive flip-flop process, must therefore occur with a half-time of less than 15 s. These findings raise doubts on the physiological role of presently discussed concepts of a carrier-mediated translocation of fatty acids across plasma membranes. PMID- 2590675 TI - Water permeabilities and salt reflection coefficients of luminal, basolateral and intracellular membrane vesicles isolated from rabbit kidney proximal tubule. AB - The mechanisms of water transport across the rabbit renal proximal convoluted tubule were approached by measuring osmotic permeabilities and solute reflection coefficients of the brush-border and the basolateral membranes. Plasma and intracellular membrane vesicles were isolated from rabbit renal cortex by centrifugation on a Percoll gradient. Three major turbidity bands were obtained: a fraction of purified basolateral membranes (BLMV), the two others being brush border (BBMV) and endoplasmic reticulum (ERMV) membrane vesicles. The osmotic permeability (Pf) of the three types of vesicle was measured using stop-flow techniques and their geometry was determined by quasi-elastic light scattering. Pf was equal to 123 +/- 8 microns/s (n = 10) for BBMV, 166 +/- 10 microns/s (n = 10) for BLMV and 156 +/- 9 microns/s (n = 4) for ERMV (T = 26 degrees C). A transcellular water permeability, per unit of apical surface area, of 71 microns/s was calculated considering that the luminal and the basolateral membranes act as two conductances in series. This value is in close agreement, after appropriate normalizations, with previously reported transepithelial water permeabilities obtained using in vitro microperfusion techniques thus supporting the hypothesis of a predominantly transcellular route for water flow across rabbit proximal convoluted tubule. The addition of 0.4 mM HgCl2, a sulfhydryl reagent, decreased Pf about 60% in three types of membrane providing evidence for the existence of proteic pathways. NaCl and KCl reflection coefficients were measured and found to be close to one for plasma and intracellular membranes suggesting that the water channels are not shared by salts. PMID- 2590676 TI - Adaptively timed conditioned responses and the cerebellum: a neural network approach. AB - Conditioned responses often reflect knowledge about the timing of a US. This knowledge is manifested in the dependence of response topography on the CS-US interval employed in training. A neural network model and set of learning rules capable of simulating temporally adaptive features of conditioned responses is reviewed, and simulations are presented. In addition, we present a neural network implementation of the model which is designed to reconcile empirical studies of long-term synaptic depression in the cerebellum with neurobiological evidence from studies of the classically conditioned nictitating membrane response of the rabbit. PMID- 2590678 TI - Evidence of chaotic dynamics underlying the human alpha-rhythm electroencephalogram. PMID- 2590677 TI - Learning and recall in a dynamic theory of coordination patterns. AB - A dynamic theory of learning and recall of coordination patterns is developed in the context of relative timing skills. Characterizing the coordination patterns in such skills by the collective variable, relative phase, we choose a model system in which the intrinsic pattern dynamics as well as the influence of environmental and memorized information are well understood from previous experimental and theoretical work. To describe learning we endow memorized information with dynamics which is determined by a phenomenological strategy. Similarly, additional degrees of freedom must be introduced to understand recall. As such recall variables we choose the relative strengths with which each memorized pattern acts on the pattern dynamics and model their dynamics phenomenologically. The resulting dynamical system that resembles models used in pattern recognition theory is shown to adequately describe the learning and recall processes. Moreover, due to the operational character of the theory, several predictions emerge that are open to experimental test. In particular, we show under which conditions phase transitions occur in the dynamics of the coordination patterns during learning and during recall. Considering different time scales and their relations we demonstrate how these phase transitions can be identified and observed. Other predictions include the influence of the intrinsic pattern dynamics on the recall process and the existence of history and hysteresis effects in recall. We discuss different forms of "forgetting" and differentiation of memorized information. The results show how a new theoretical view of learning and recall as change of behavioral dynamics can lead to a different understanding of these processes by providing testable predictions. PMID- 2590680 TI - Conduction along myelinated and demyelinated nerve fibres during the recovery cycle: model investigations. AB - The membrane excitability changes as well as the underlying mechanisms of these changes in a normal and in a systematically paranodally demyelinated nerve fibre have been investigated by paired stimulation during the first 30 ms of the recovery cycle. The ionic current kinetics determining the observed changes in the action potential parameters are presented also. The simulation of the conduction in the normal fibre is based on the Frankenhaeuser and Huxley (1964) and Goldman and Albus (1968) equations, while in the case of a demyelinated fibre according to the same equations modified by Stephanova (1988a). It has been shown for the demyelinated membrane that increased demyelination increases both the threshold current for the second potential as well as the absolute refractory period. With increasing interpulse interval, the subnormality of the membrane excitability is followed by supernormality in the case of the demyelinated membrane. For the recovery cycle of 30 ms under consideration no supernormality of the normal membrane excitability is obtained. With interpulse interval from 8.8 to 10.9 ms, the highest degree of demyelination (l = 30 microns) is accompanied by a refractory period of transmission. The membrane properties of the normal and demyelinated fibres recover 20 ms after the first pulse. For short interpulse intervals, the amplitude of the second action potential is decreased, and a slower propagation velocity is obtained. The most sensitive phenomenon is the excitability of the demyelinated membrane, which remains unrecovered 30 ms after the first pulses has been applied. PMID- 2590679 TI - Lumped versus distributed thermoregulatory control: results from a three dimensional dynamic model. AB - In this study we use a three-dimensional model of the human thermal system, the spatial grid of which is 0.5 ... 1.0 cm. The model is based on well-known physical heat-transfer equations, and all parameters of the passive system have definite physical values. According to the number of substantially different areas and organs, 54 spatially different values are attributed to each physical parameter. Compatibility of simulation and experiment was achieved solely on the basis of physical considerations and physiological basic data. The equations were solved using a modification of the alternating direction implicit method. On the basis of this complex description of the passive system close to reality, various lumped and distributed parameter control equations were tested for control of metabolic heat production, blood flow and sweat production. The simplest control equations delivering results on closed-loop control compatible with experimental evidence were determined. It was concluded that it is essential to take into account the spatial distribution of heat production, blood flow and sweat production, and that at least for control of shivering, distributed controller gains different from the pattern of distribution of muscle tissue are required. For sweat production this is not so obvious, so that for simulation of sweating control after homogeneous heat load a lumped parameter control may be justified. Based on these conclusions three-dimensional temperature profiles for cold and heat load and the dynamics for changes of the environmental conditions were computed. In view of the exact simulation of the passive system and the compatibility with experimentally attainable variables there is good evidence that those values extrapolated by the simulation are adequately determined. The model may be used both for further analysis of the real thermoregulatory mechanisms and for special applications in environmental and clinical health care. PMID- 2590681 TI - [The role of protein phosphorylation in mast cell secretion, stimulated by concanavalin A. Connection to the cytoskeleton]. AB - The role of cytoskeleton and protein phosphorylation in concanavalin A and phorbol ester (PMA) induced mast cell secretion was investigated. It was shown that the receptor coupled with lectin interacts with the cytoskeleton. When the ligand-receptor complex is formed, an increased phosphorylation of some proteins is induced. The same proteins are phosphorylated under the influence of PMA, a protein kinase C activator, thus suggesting that protein kinase C is involved in the regulation of mast cell exocytosis. The results obtained testify to the effect that the mechanism of mast cell degranulation induced by concanavalin A is due to modification of the cytoskeleton. PMID- 2590682 TI - [Phosphorylation of isolated components of the troponin complex of skeletal and cardiac muscle phosphorylase kinase from bird skeletal muscles]. AB - Pigeon and chicken skeletal muscle phosphorylase kinase purified to a nearly homogeneous state is able to phosphorylate both cardiac and skeletal troponin I and T. After 1-hr incubation, the enzyme transfers up to 0.35 mole of phosphorus per mole of skeletal troponin I, up to 0.5 mole of cardiac troponin I and up to 0.1 mole of cardiac and skeletal troponin T. Avian muscle phosphorylase kinase does not phosphorylate the first serine residue of cardiac and skeletal troponin T, but catalyzes the phosphate incorporation into the site(s) of troponin T located in the central or C-terminal parts of the protein molecule. The rate of troponin phosphorylation by pigeon muscle phosphorylase kinase is pH-dependent: the 6.8/8.2 ratio for troponin I is close to 0,2, whereas that with troponin T varies in the range of 0.5-0.7. Troponin phosphorylation by avian phosphorylase kinase depends on the presence of Ca2+ in the incubation mixture. In the presence of 3 mM EGTA troponin I phosphorylation is inhibited by 70-90%, whereas that of troponin T--by 50%. The experimental results indicate that the phosphorylation of troponin I and T is catalyzed either by two different active centers or by different conformations of the single center of avian phosphorylase kinase. PMID- 2590683 TI - [The effect of anthracyclines on heart mitochondria respiration during the action of creatine phosphokinase]. AB - It was shown that during glutamate+malate oxidation in the presence of creatine, antitumour anthracycline antibiotics strongly inhibit the rate of oxygen uptake by rat heart mitochondria; ADP excess activated the respiration up to the initial level, i.e., that observed after the first addition of ADP. Carboxyatractyloside addition to a system containing creatine (or hexokinase+glucose) results in the stimulation of rubomycin-induced mitochondrial respiration. Substitution of carboxyatractyloside by oligomycin gives very similar results. It is supposed that anthracycline antibiotics exert a manyfold effect on heart mitochondrial membranes which results in impaired compartmentation of enzymatic systems providing for oxidative phosphorylation. PMID- 2590684 TI - [Cytochrome P-450 in proteoliposomes: oligomeric structure of the LM2 isoform]. AB - Crosslinking of protein molecules with bifunctional reagents and subsequent electrophoresis of the modified proteins revealed the presence of cytochrome P 450 LM 2 oligomers in proteoliposome membranes obtained in different ways and differing in their phospholipid composition. Data from a comparative analysis of cytochrome P-450 oligomeric structures in solution and in membrane are suggestive of the hexameric organization of cytochrome P-450 LM 2 within proteoliposome membranes. PMID- 2590685 TI - [Detection of a sodium pump in the terminal segment of the bacterial respiratory chain]. AB - An alkalo- and halotolerant aerobic microorganism has been isolated which, according to microbiological data and the ribosomal 5S-RNA sequence, is a Bacillus similar, but not identical, to B. licheniformis and B. subtilis. The microorganism termed as Bacillus FTU proved to be resistant to the protonophorous uncoupler CCCP. The fast growth of Bacillus FTU in the presence of CCCP was shown to require high Na+ concentrations in the medium. A procedure has been developed to exhaust endogenous respiratory substrates in Bacillus FTU cells so that fast oxygen consumption by the cells was observed only upon addition of an exogenous respiratory substrate. The exhausted cells were found to oxidize ascorbate in the presence of TMPD in a cyanide-sensitive fashion. Ascorbate oxidation was coupled to the uphill Na+ extrusion stimulated by CCCP and a penetrating weak base, diethylamine (DEA), as well as by valinomycin with or without DEA. The operation of the Bacillus FTU terminal oxidase resulted in the generation of delta psi which, in a Na+ medium, was slightly decreased by CCCP and strongly by CCCP + DEA. In a K+ medium CCCP discharged delta psi even without DEA. Ascorbate oxidation was competent in ATP synthesis which was resistant to CCCP in the Na+ medium and sensitive to CCCP in the K+ medium. CCCP + DEA were inhibitory in both media. The data obtained indicate that there is a Na+-motive terminal oxidase in Bacillus FTU. It is suggested that delta microNa formed by the oxidase can be utilized by an Na+-driven ATP-synthase. PMID- 2590686 TI - [Two qualitatively different structuro-functional states of mitochondria]. AB - Low (120 mosM) tonicity of incubation media of mitochondria was found to be associated with anomalous phase transition at 19--26 degrees C. A rise in temperature caused a decrease in the pyrene excitation in border lipids of the mitochondrial membrane. Within this temperature range the quenching of intrinsic protein fluorescence by pyrene was sharply decreased. It may be inferred from these data that at 100mosM tonicity and temperatures below 19 degrees C, mitochondrial membrane proteins are in an aggregated state. At temperatures above phase transition protein deaggregation takes place. It was shown that a decrease in tonicity from 300 to 120 mosM at 15 degrees C or a rise in temperature from 15 degrees to 37 degrees C at 300 mosM tonicity increased the phosphorylation of the 52 kDa mitochondrial protein. It was assumed that swelling of mitochondria in hypotonic media simulates one of the steps of the hormone-induced signal transfer in mitochondria in vivo. PMID- 2590687 TI - [Stimulation of spreading and aggregation of platelets on immobilized type V collagen: mechanisms depending on Ca2+ and protein kinase C]. AB - The effects of phorbol ester (PMA) and stable prostaglandin endoperoxide analog (U46619) on platelet interaction with a surface coated with monomeric type V collagen (CV substrate) and free Ca2+ concentration in platelet cytoplasm ([Ca2+]in) have been studied. In the absence of PMA and U46619, the discoid and spherical platelets from suspension are attached to CV substrate but are incapable of spreading and aggregation on the substrate. An addition of PMA (0.15 1.5 nM) or U46619 (1.5 microM) to the reaction mixture stimulates platelet spreading and the formation of multilayer (thrombi-like) aggregates on CV substrate. Using the fluorescent probe Quin 2, it was found that U46619 (0.1 microM) increases [Ca2+]in from the basal level (100-120 mM) to 600 nM. PMA (0.75 15 nM) exerts only a slight effect increasing [Ca2+]in by 30-40 nM. The data obtained suggest that the PMA-induced spreading and aggregation of platelets on CV substrate can occur via activation of protein kinase C at relatively low [Ca2+]in values. These results also testify to the existence of a substrate independent mechanism of spreading of platelets activated in suspensions by soluble inducers. PMID- 2590688 TI - [One- and two-electron reduction of ubiquinone homologs by NADH- dehydrogenase preparations from the mitochondrial respiratory chain]. AB - The mechanism of ubiquinone homologs reduction by different preparations of mitochondrial NADH dehydrogenase: complex I within submitochondrial particles, isolated NADH-ubiquinone oxidoreductase and soluble low molecular weight NADH dehydrogenase, has been investigated. It has been shown that NADH oxidation via the rotenone-insensitive reaction is associated with one-electron reduction of low molecular weight ubiquinone homologs (Q0, Q1, Q2) to semiquinone with subsequent fast oxidation of the latter by atmospheric oxygen to form a superoxide radical. The two-electron ubiquinone reduction to quinol in the rotenone-sensitive reaction is unaccompanied by the semiquinone release from the enzyme active center into the surrounding solution. PMID- 2590689 TI - Differentiation of pure chick embryo epidermis grown in primary serum-free culture. AB - The differentiation of precocious embryonic epidermis in serum-free primary culture was analyzed by light and electron microscopic methods. Explants of 7-day chick embryo epidermis were grown on collagen or poly-L-lysine substrates in the absence of dermal mesenchyme. The serum substitute consisted of a mixture of insulin, transferrin, putrescine and seleneous acid together with (or without) Nerve Growth Factor. These culture conditions were shown to support proliferation, growth and development (evaluated using morphological criteria) of the epidermal explants up to 4-5 days; during this period, the epidermis underwent stratification; well-developed desmosomes as well as tonofilaments were formed and the epidermis achieved a morphology close to that of 10-11 day epidermis in ovo. However long-term survival of the explants was not obtained as cellular death, starting on day 5, progressively led to the necrosis of most parts of the explant. This morphological study demonstrates that the early phases of epidermal growth and maturation can occur to some extent in the virtual absence of dermal elements and serum factors. Chick embryo epidermal cells may thus possess the intrinsic ability to go through, at least for short periods in vitro, their differentiation programme. Then, at the onset of epidermal keratinization (12 days in ovo), they require specific exogenous factors to fully differentiate in vitro. PMID- 2590690 TI - Auditory P300 does not differentiate borderline personality disorder from schizotypal personality disorder. AB - The P300 response to an auditory two-tone discrimination task has previously been reported to have prolonged latency and reduced amplitude in schizophrenia and borderline personality disorder. In this study, P300 was recorded from 23 subjects with borderline personality disorder, 12 subjects fulfilling criteria for both borderline and schizotypal personality, and 11 subjects with schizotypal personality. The mean P300 latency was similar in each of these groups and was significantly longer than in 32 patients with neuroses and other personality disorders and 74 nonpatient controls. These findings suggest that borderline and schizotypal patients share a similar abnormality in auditory stimulus evaluation and question whether or not these disorders are separate. PMID- 2590691 TI - Development of water dysregulation during Arieti's third stage of schizophrenia? AB - We found abnormal diurnal weight gain among 25% of acutely psychotic patients with schizophrenia and 68% of chronically psychotic patients with schizophrenia. They were weighed at 7:00 AM and 4:00 PM weekly for 3 weeks. We normalized the diurnal weight gain (NDWG) as a percentage by subtracting the 7:00 AM weight from the 4:00 PM weight, multiplying the difference by 100, and dividing the result by the 7:00 AM weight, NDWG was 0.93% +/- 0.89% for the 36 acutely psychotic patients and 2.2% +/- 1.5% for the 68 chronically psychotic patients (F = 25.297, p less than 0.0001). Drugs did not explain this difference. Our data, though preliminary, suggest that water dysregulation, as manifested by abnormal diurnal weight gain, develops in schizophrenia as patients progress into Arieti's third stage of this disorder. A longitudinal study design, rather than our cross sectional one, would be necessary to assess developmental changes in schizophrenia. PMID- 2590692 TI - Osteopenia, pathological fractures, and increased urinary calcium excretion in schizophrenic patients with polydipsia. AB - Ten male chronic schizophrenic patients with polydipsia and 10 nonpolydipsic controls, matched for gender, diagnosis, duration of illness, age, and race, were studied by dual- and single-photon absorptiometry to estimate bone density of the lumbar spine and radius and by 24-hr urine collections to estimate urinary electrolyte excretion. Bone density was normal in the control group, but was abnormally low in the polydipsic group, which had a markedly increased incidence of fractures. Electrolyte excretion was normal in the control group and in the polydipsic group when water intake was restricted to normal amounts; increased urinary sodium and calcium excretion occurred in proportion to polydipsia. As polydipsia is associated with a number of physiological changes, the cause of the osteopenia is unclear; we suggest that a negative calcium balance caused by increased urinary calcium excretion induced by extracellular space expansion may play an important role in the causation of the skeletal changes. PMID- 2590693 TI - The effect of antidepressants on immune function in mice. AB - Depression or its treatment with antidepressant agents may have an impact on the normal function of the immune system. To address this issue in an animal model, we studied the effect of maprotiline and desipramine treatment of mice on several immunological activities associated with host resistance to cancer and infections. Our results indicate that chronic maprotiline treatment depressed natural killer (NK) cell function, measured in vivo as clearance of tumor cells from the lung or in vitro as cytolytic activity. Cell-mediated immunity, measured as delayed hypersensitivity in vivo and T and B lymphocyte proliferative responses in vitro, was largely unaffected. Although antidepressant toxicity at high concentrations inhibited T, B, and NK cell activity, it is unlikely that this is the basis for the in vivo effects. PMID- 2590694 TI - Adrenocortical and behavioral responses to repeated stressors: toward an animal model of chronic stress and stress-related mental illness. AB - Research in chronic stress has been hampered by the absence of an operational definition for that condition. To explore possible criteria for chronic stress, we repeatedly exposed rats to 2 hr of tail shock per day. After several days, we found elevated prestress corticosterone levels and abnormal behavior, including decreased food consumption, fear-like suppression of activity immediately before stress, greater hesitancy to drop from a suspended wire, and decreased exploratory behavior in a novel environment. A less intensely stressed group of rats also had elevated prestress corticosterone levels, but not the abnormal behaviors that persisted in shocked rats after the stress sessions were discontinued. We propose that abnormalities in both adrenocortical function and behavior are a better marker for chronic stress than abnormalities in either of these systems alone. The animal model we have described may be useful for studying factors that contribute to development of chronic stress or PTSD. PMID- 2590695 TI - Cocaine-induced delirium versus delusional disorder. PMID- 2590696 TI - ECT seizure monitoring. PMID- 2590698 TI - Headache in schizophrenia and seasonality of births. PMID- 2590697 TI - Methylene blue excretion in depression. PMID- 2590700 TI - "Initial-" and "change-orienting reactions": an analysis based on visual single trial event-related potentials. AB - The present study was concerned with brain potentials elicited by, respectively, the first of a series of stimuli ("initial-orienting reaction", I-OR), and infrequent deviants ("change-orienting reaction", C-OR). Single-trial event related potentials (ERPs) to visual stimuli were estimated from recordings at Oz, Pz, Cz and Fz. The design included both a habituation series as well as a series of occasional deviant trials against a background of standards. This was done with both task-relevant and neutral stimuli, and in two interstimulus interval (ISI) conditions: 2.45 s and 8.45 s. In the latter ISI condition, skin conductance responses (SCRs) were recorded as well. Decrease (Habituation) in the habituation series was found for a non-specific N1, a posteriorly distributed P3, and the SCR, but not for P2-N2. Deviant stimuli produced an enhancement of the central P2-N2, the P3, the N1 (on the first few deviant trials only, in both ISI conditions), and the SCR (with task-relevant stimuli only). Elongation of ISI delayed both short-term and long-term decrease of P3, but had no effect on enhancement of P2-N2 due to stimulus deviance. It was concluded that, with respect to ERP parameters, the I-OR is marked by the N1, whereas the C-OR coincides with the P2-N2. PMID- 2590699 TI - DST and schizophrenic symptomatology. PMID- 2590701 TI - Event-related potentials before and after training: chronometry and lateralization of visual N1 and N2. AB - Event-related potentials (ERPs) were recorded from normal right-handed males in visual-matching tasks before and after training to a high level of automaticity. The amplitude and latency of the left and right hemispheric N1 and N2 components were analyzed. While changes of N1 "after training" relative to "before training" were statistically non-significant, the N2 component appeared to be a sensitive indicator of the variability in chronometry and lateralization of cerebral processes modified by training. The N2 results suggest that with practice the physiological processes underlying performance in a visual-cognitive task become more efficient, selective and localized. PMID- 2590702 TI - Nicotine regulation among heavy and light smokers in a non-stressful environment. AB - The purpose of this study was to assess nicotine regulation among "heavy" and "light" smokers. Previous studies supporting the nicotine regulation model of smoking behavior have suggested that smokers compensate for a reduction in the amount of nicotine available in their cigarette by altering smoking frequency, puff volume, or other aspects of smoking topography. However, little is known about a smoker's decision to smoke a specific cigarette, and the concurrent changes in their blood nicotine. Manipulation of nicotine levels in the blood could play a critical role in smoking maintenance, by regulating the extent and quality of the CNS effects of smoking. In this study, 24 heavy and light smokers (cotinine above or below 260 ng/ml) smoked high- (1.0 mg) or low- (0.5 mg) dose nicotine cigarettes while watching non-stressful movies. Blood nicotine was assessed before and after smoking a preload and free operant cigarette. The results showed that blood nicotine levels after smoking the free operant cigarette were significantly more consistent (lower standard error) for the heavy smokers, following a low dose, as opposed to a high-dose preload. Light smokers showed a non-significant trend towards being more consistent when the high-dose nicotine preload was used. This suggests that heavy smokers may have maximized their dose of nicotine whenever available nicotine was in relatively short supply (low dose condition). However, light smokers may have minimized their exposure when available nicotine was relatively more plentiful (high dose condition). PMID- 2590703 TI - Methods and mechanisms in electrodermal omission responding: a commentary on stimulus omission and the orienting response by Barry and O'Gorman. AB - Barry and O'Gorman (1987) have employed a response-averaging technique to demonstrate that electrodermal orienting responses (ORs) to omitted stimuli have unusually long latencies. They suggest that this latency delay provides evidence that omission ORs are "voluntary" responses initiated after a process of significance evaluation. The present commentary is addressed to both the methodological and theoretical aspects of their work. Firstly, some of the disadvantages of response averaging with electrodermal measures are reviewed, particularly as applied to omission ORs. Secondly, the use of OR latency as a dependent measure is discussed within an information-processing context. It is concluded that the assessment of stimulus significance does not systematically influence the latency of the OR. Hence, delayed latencies for omission responses probably reflect inaccuracies in the estimation of long inter-stimulus intervals, rather than a process of significance evaluation unique to the omission OR. PMID- 2590704 TI - Methods and mechanisms in electrodermal studies of omission responding. AB - Barry and O'Gorman (1987) employed a response-averaging technique to investigate the electrodermal orienting response (OR) to stimulus omission. We obtained reliable evidence of increased response latency to stimulus omission, supporting an explanation of the missing-stimulus effect in terms of Maltzman's voluntary OR. Wilson's (1989) commentary on our article addresses both methodological and theoretical aspects. This response first examines his methodological difficulties, and provides simulation exercises which serve as a validation of our procedure. We then examine Wilson's theoretical points. His alternative theoretical explanation of the missing-stimulus effect, in terms of a systematic bias in the time-keeper of the stimulus-comparator process, is shown to be untenable. His remaining problem, concerning what he terms "assessment of stimulus significance", appears to have arisen through misinterpretation of our theory. A clarification of our theoretical position indicates the internal consistency of our use of "significance" and "voluntary OR". PMID- 2590705 TI - Extracranial and digital vascular events: an analysis of methods in BVP amplitude and biofeedback research. AB - The purpose of the present study was to assess and compare the effects of within and between-session exposure to environmental context on left temporal artery pulse amplitude, right temporal artery pulse amplitude, and left digital pulse amplitude. Subjects were individually tested for 20 min daily over a period of eight consecutive days. A significant interaction was found for Position X Interval. These results show that exposure to the experimental context occurs with diametrically opposite effects on temporalis and digital pulse amplitude within session. Moreover, these results would support the hypothesis that controversial findings within the headache and biofeedback literature may be partially attributable to methodological differences where, for example, different authors use different transducer locations and/or evaluate pulse amplitude at different points within or among sessions. Indeed, research on the effects or lack thereof of therapeutic manipulations may have little or nothing to do with the intervention or experimental manipulations themselves. These effects may be masked or augmented by subject and methodological confounds during baseline and testing conditions. PMID- 2590706 TI - Parietal processing of affect and cognition: cerebral organization in strongly lateralized left-handed subjects. AB - Cerebral organization for the processing of emotion and for the differential processing of affect and cognition have thus far been studied exclusively in right-handed subjects. Since handedness is related to cerebral dominance, our understanding of the neural processing of affect and cognition should be further enhanced by the study of sinistral subjects. The present study examined the differential parietal processing of emotional stimuli under affective and cognitive conditions in left-handed subjects. The subjects were exposed to emotional stimuli presented under affective and cognitive instructional sets and to neutral, control stimuli. Bilateral electroencephalographic and bilateral electrodermal activity data showed greater responsiveness to emotional than neutral stimuli but no differential lateralization of affect and cognition in left-handed subjects. Results also showed that female subjects were more responsive to emotional stimuli than male subjects. Results were interpreted as suggesting that left-handed individuals may be less strongly lateralized for the differential processing of affect and cognition than right-handed individuals and that females may have greater focal organization for the processing of emotion than males. PMID- 2590707 TI - Accessing previous mental sleep experience in REM and NREM sleep. AB - This study investigated the processes by which contents previously stored in memory are retrieved and inserted into mental sleep experience (MSE). MSE reports were collected from six subjects awakened three times on each of eight nights in two alternate sequences of awakenings (NREM-REM-NREM; REM-REM-REM). The occurrences of interrelations between contents of report pairs were scored using Clark's (1970) feature matching model. These were greater for same night pairs than for different night pairs, and did not differ with respect to sequence of awakenings or order of report pairs (first-second, second-third, first-third). Contents of previous MSEs, therefore, seem to be accessible in both sleep types for insertion into current MSE. The interrelated units were more frequently lexical than propositional, with more paradigmatic than syntagmatic relationships in report pairs from both sequences of awakenings. Thus, the re-elaboration of contents of previous MSEs seems to occur mainly at the level of single contents in both types of sleep, with similar modalities of processing. PMID- 2590708 TI - Awareness of the CS-UCS contingency and classical conditioning of skin conductance responses with olfactory CSs. AB - The possibility of demonstrating acquisition of classically conditioned responses without awareness of the conditioned stimulus-unconditioned stimulus (CS-UCS) contingency using olfactory stimuli with 58 college student subjects was tested. A classical discrimination delay conditioning paradigm was employed, with electric shock as the UCS and two pleasant odors (perfumes) as the conditioned stimuli (CS+ and CS-). Trial-by-trial measures of skin conductance conditioned responses served as dependent variables. A masking task in the form of an olfactory memory task was employed for the purpose of delaying the onset of awareness of the conditioning contingency. Awareness of the conditioning contingency was assessed by a concurrent and a post hoc measure, and subjects who satisfied both criteria were considered aware of the CS-UCS contingency. Conditioning was observed only in the aware subjects, and only after the onset of awareness of the CS+-UCS contingency. Respiratory activity, measured as a check against possible artifacts, had no effect on the SCR measures. It was concluded that the awareness of the CS-UCS contingency is necessary for acquisition of discriminative conditioned responses in humans, regardless of the sensory modality in which CSs are presented. Sex differences in skin conductance measures and performance on the olfactory memory task were observed. PMID- 2590709 TI - Embryos of different ages transferred to the rat oviduct enter the uterus at different times. AB - Indirect evidence of embryo signalling to the oviduct was sought in rats by examining the transport of embryos of different ages. One-cell or four-cell embryos were transferred to the oviducts of recipient rats on Day 1 of pregnancy, and the number, condition, and location of native and transferred embryos was assessed on Day 4. To control for the effect of the presence of foreign embryos and excess number of eggs and the transfer procedure upon the fate of native embryos, other groups of rats were sham-operated or left undisturbed. Recipients had a mean number of ova significantly higher than controls. In controls and recipients of 1-cell embryos, the majority of eggs reached the morula stage and all of them were located in the oviducts. In those animals receiving 4-cell embryos, half of the eggs had reached the blastocyst stage and 28% were in the uteri (p less than 0.005). These results support the idea that advanced embryos can influence the timing of their entrance to the uterus in rats. PMID- 2590710 TI - Multiple classes of prostaglandin F2 alpha binding sites in subpopulations of ovine luteal cells. AB - A cryostorage procedure was developed to provide ovine luteal cells throughout the period of seasonal anestrus. Corpora lutea obtained from midluteal phase, superovulated ewes were dispersed enzymatically. Some dispersed cells were fractionated into subpopulations by elutriation. Dimethylsulfoxide (7.5% final concentration) in Hanks' buffered saline was added to cells at 4 degrees C, and dispersed cell preparations were frozen in a programmable cell freezer and stored at -196 degrees C. After recovery from cryopreservation, cell viability and prostaglandin F2 alpha (PGF2 alpha) binding characteristics of thawed cells were not different from those of corresponding fresh cells. Additionally, thawed cells retained the capacity to attach to culture dishes and retained responsiveness of progesterone secretion to prostaglandin E2 (PGE2) and ovine luteinizing hormone (LH), although rates of progesterone secretion were attenuated in thawed compared with fresh cells. The cryopreservation procedure will prove useful to relieve constraints in utilization of ovine luteal cells arising from reproductive seasonality in sheep. Cells retrieved from cryostorage were evaluated by studying PGF2 alpha binding characteristics. From saturation analyses (increasing amounts of radiolabeled PGF2 alpha) of PGF2 alpha binding to unfractionated cells, we detected a single class of high affinity binding sites (Kd = 17.4 +/- 2.3 nM) in addition to the nonspecific binding component. Using displacement analyses (constant radiolabeled PGF2 alpha and increasing amounts of unlabeled PGF2 alpha) and unfractionated cells, we detected additional binding sites of lower affinity (Kd = 409 +/- 166 nM) as well as the nonspecific binding component. Small luteal cells obtained by elutriation, which were essentially devoid of large cell contamination, had only low affinity binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590711 TI - Luteal production of steroids and prostaglandins during simulated early pregnancy in the primate: differential regulation of steroid production by chorionic gonadotropin. AB - Stimulation of the primate corpus luteum (CL) by endogenous chorionic gonadotropin (CG) in early pregnancy, or by exogenous human (h)CG in simulated early pregnancy, results in a transient elevation of serum progesterone (P) and a persistent elevation of serum 17 beta-estradiol (E). Luteal prostaglandins (PG) may play a role in these responses. The objective of the current study was to correlate luteal PG production and steroidogenic response of CL in vitro with patterns of serum steroids during simulated early pregnancy. CL were removed from rhesus monkeys (n = 26) at 0 h, 9 h, 3 days, 6 days, and 10 days, during prolonged CG exposure of simulated early pregnancy. Dispersed cells were incubated in vitro at 37 degrees C for 8 h. Changes in basal production of P were not significantly correlated with patterns of serum steroids. Maximal stimulation of P production by hCG in vitro (stimulated minus basal) continuously declined (p less than 0.01) from 0 h (means +/- SE, 59.6 +/- 17.9 ng/ml) to 10 days (4.7 +/- 1.8 ng/ml) of simulated early pregnancy. In contrast to patterns of response to hCG, the level of enhancement in P production in response to a maximally stimulatory dose of dibutyryl (db) cyclic adenosine 3',5'-monophosphate (cAMP) declined (p less than 0.05) from 0 h (52.4 +/- 17.6 ng/ml) to 3 days (20.3 +/- 8.4 ng/ml), but was maintained through 10 days (23.7 +/- 11.6 ng/ml) of simulated early pregnancy. As such, desensitization to gonadotropin, which occurred in terms of P production, appears to involve an event subsequent to stimulation of adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590712 TI - Nuclear transplantation in early pig embryos. AB - Nuclear transfer was evaluated in early porcine embryos. Pronuclear stage embryos were centrifuged, treated with cytoskeletal inhibitors, and subsequently enucleated. Pronuclei containing karyoplasts were placed in the perivitelline space of the enucleated zygote and fused to the enucleated zygote with electrofusion. The resulting pronuclear exchange embryos were either monitored for cleavage in vitro (9/13 cleaved and contained 2 nuclei after 24 h, 69%) or for in vivo development. In vivo development after 3 days resulted in 14/15 (93%) of the embryos transferred cleaving to the greater than or equal to 4-cell stage and after 7 days 6/16 (38%) reaching the expanded blastocyst stage. A total of 56 pronuclear exchange embryos were allowed to go to term, and 7 piglets were born. A similar manipulation procedure was used to transfer 2-, 4- or 8-cell nuclei to enucleated, activated meiotic metaphase II oocytes. Enucleation was effective in 74% (36/49) of the contemporary oocytes. Activation was successful in 81% (37/46) of nonmanipulated but pulsed oocytes versus 13% (4/31) of control oocytes (p less than 0.01). After 6 days in vivo, 9% (1/11) of the 2-cell nuclei, 8% (7/83) of the 4-cell nuclei, and 19% (11/57) of the 8-cell nuclei transferred to enucleated, activated meiotic metaphase II oocytes resulted in development to the compact morula or blastocyst stage (p less than 0.01). A total of 88 nuclear transfer embryos were transferred to recipient gilts for continued development. A single piglet was born after the transfer of a 4-cell nucleus to an enucleated, activated metaphase II oocyte and subsequent in vivo development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590713 TI - Early embryonic development in vitro by coculture with oviductal epithelial cells in pigs. AB - This experiment was designed to evaluate the ability of three different somatic cell cultures to promote development of early cleavage stage pig embryos. A total of 245 2-cell, 4-cell, 8-cell, and 16-cell pig embryos were cocultured for 5 days with porcine oviductal epithelial cells (POEC), porcine fetal fibroblast monolayer (PEF), a combined POEC and PEF coculture system (PEF-POEC), or Dulbecco's Modified Eagle Medium alone (DMEM). Embryos were collected at slaughter from the reproductive tracts of superovulated prepubertal gilts. Embryos were recovered, evaluated, and randomly placed in one of the four treatment groups. POEC were recovered from oviductal flushes, washed, and placed in 24-well plates. PEF were obtained from 30-day to 60-day fetuses and established in culture. Finally, PEF-POEC consisted of a confluent monolayer of PEF in the bottom of 24-well plates also containing a Costar semipermeable membrane chamber with POEC in it. Embryos were evaluated every 24 h to determine stage of development. More (p less than 0.05) embryos developed to blastocysts in POEC (70% and 54%, respectively) and PEF-POEC (67% and 61%, respectively), than in either DMEM (16% and 2%, respectively) or PEF (27% and 23%, respectively). However, development of embryos did not differ (p less than 0.05) for POEC and PEF-POEC. These data indicate the presence of a primary culture of POEC promotes in vitro development of early cleavage stage pig embryos. PMID- 2590714 TI - Difference in luteinizing hormone response to an opioid antagonist in beef heifers and cows. AB - In three experiments, we examined endogenous opioid inhibition of luteinizing hormone (LH) secretion during the bovine estrous cycle. An increase in serum LH in response to the opioid antagonist naloxone (Na; 1 mg/kg i.v.) was the criterion for opioid inhibition. Estrous cycles were synchronized via prostaglandin administration. In Experiment 1, mean serum LH was not different during the luteal phase in yearling heifers (n = 6/group) at Hour 1 after Nal (2.1 ng/ml) compared to controls (1.8 ng/ml). However, LH peak amplitude was increased (p less than 0.05) in the Nal compared to the control group. Serum LH was increased (p less than 0.01) during the follicular phase in heifers at Hour 1 post-Nal compared to controls (4.7 and 3.5 ng/ml, respectively). Again, Nal administration was followed by increased (p less than 0.05) LH pulse amplitude compared to control. In Experiment 2, no effect of Nal upon serum LH was detected in cows (n = 9) during proestrus, metestrus, midluteal and late luteal portions of the estrous cycle. In Experiment 3, the LH response to Nal was examined simultaneously in yearling heifers and cows (n = 5/group) during the luteal and follicular phases. Serum LH increased (p less than 0.001) during Hour 1 post-Nal in heifers compared to cows during the follicular (3.4 vs. 1.7 ng/ml) but not during the luteal phase. LH pulse amplitude also increased (p less than 0.05) during Hour 1 post-Nal in heifers compared to cows during the luteal (2.5 vs. 1.1 ng/nl and follicular (2.5 vs. 1.3 ng/ml) phases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590716 TI - Immunolocalization and concentrations of inhibin alpha in the ovine testis and excurrent duct system. AB - Inhibin was localized in the ovine testis, excurrent ducts, and accessory sex glands by using a rabbit antiserum against a synthetic polypeptide representing the first 30 amino acids of porcine inhibin alpha-subunit. Concentrations of inhibin in fluids entering and leaving the epididymis also were determined in a radioimmunoassay using the same antibody. In the testis, immunostaining of inhibin was conspicuous in the seminiferous epithelium. Leydig cells occasionally were stained and the tunica media of blood vessels always was stained. Intense staining was observed in the epithelia lining the rete testis and ductuli efferentes. Staining also was intense in the epithelium of the initial segment and proximal caput epididymidis, and became less intense along the length of the epididymis. These observations were consistent with concentrations of inhibin in rete testis fluid (8.2 pmol/ml) entering the ductuli efferentes and in cauda epididymal plasma (0.67 pmol/ml) leaving the epididymis. Epithelia of ampullary and vesicular glands and of some prostatic acini were positively stained, but bulbourethral glands were never stained. Adrenal cortex, some proximal convoluted tubules in the kidney, and transitional epithelium of the urethra also were stained. Based on radioimmunoassay data and fluid flow rates for the ram, it was concluded that almost all of the 328 pmol inhibin that enters the ductuli efferentes daily is endocytosed in the proximal parts of the excurrent duct system. The physiological role(s) for inhibin, or inhibin-like peptides, in the excurrent duct system remains speculative. PMID- 2590715 TI - Identification and mechanism of action of phospholipids capable of modulating rat testicular microsomal 3 beta-hydroxysteroid dehydrogenase-isomerase activity in vitro. AB - Rat testicular 3 beta-hydroxysteroid dehydrogenase-isomerase (3 beta-HSD Isomerase) converts pregnenolone to progesterone. The enzyme is localized to the microsomal membranes of testicular homogenates, and treatment of the microsomes with phospholipases causes a reduction in 3 beta-HSD-Isomerase activity. The relationship between the membrane microenvironment and 3 beta-HSD-Isomerase activity was investigated by adding phospholipids of known structure to microsomal incubations and determining the effects on the conversion of pregnenolone to progesterone. Phosphatidylcholines with saturated acyl chains of 8, 10, 12, and 14 carbon atoms, or unsaturated chains, were extremely inhibitory to 3 beta-HSD-Isomerase, causing reductions in specific activity to 10-40% of the control value. Furthermore, the inhibition appeared to be caused primarily by a reduction in the active enzyme concentration (Vmaxapp). Phosphatidylcholines with longer saturated acyl chains were without effect. Phosphatidylserine and phosphatidic acid were activators of 3 beta-HSD-Isomerase. These phospholipids decreased the Kmapp value (to 21% and 43% of control values, respectively), suggesting that the enhancement of 3 beta-HSD-Isomerase activity was through an active-site-oriented effect. Furthermore, for phosphatidic acid to activate 3 beta-HSD-Isomerase, saturated acyl chains of 16 carbon atoms were necessary, other configurations being slightly inhibitory. The remarkable specificity for certain phospholipid configurations and the different effects of these membrane components suggest that androgen biosynthesis may be regulated by changes in the phospholipid microenvironment of 3 beta-HSD-Isomerase. PMID- 2590717 TI - Porcine zona pellucida: association of sperm receptor activity with the alpha glycoprotein component of the Mr = 55,000 family. AB - The immunogenicity and sperm receptor activity of five preparations of the major porcine zona pellucida glycoprotein family ZP3 (Mr = 55,000) were investigated. These included (1) ZP3, a chromatographically purified preparation of the 55,000 family; (2) ZP3 alpha, and (3) ZP3 beta, the two-component glycoproteins of the ZP3 family; (4) ZP3-EBGD, a partially deglycosylated preparation of ZP3 obtained by enzymatic treatment; and (5) ZP3-DG, a chemically deglycosylated preparation of ZP3. Titer studies using mouse and rabbit antisera prepared against each preparation yielded the following order of immunogenicity: ZP3 and ZP3 beta greater than ZP3-EBGD and ZP3 alpha greater than ZP3-DG, indicating that ZP3 becomes less immunogenic as more carbohydrate is removed. Pretreatment of intact zona with the various antisera prior to zona exposure to sperm resulted in an inhibition of sperm attachment to those zona treated with antibodies to ZP3, ZP3 EBGD, and ZP3 alpha. Pretreatment of zona with antibodies to ZP3 beta and ZP3-DG had no effect on sperm attachment. Studies involving pretreatment of boar sperm with the various ZP3 preparations prior to their use in a sperm-zona attachment assay and investigations involving displacement of the radiolabeled ZP3 preparations from sperm by unlabeled ZP3 preparations also yielded findings similar to the antibody studies. Collectively, these data indicate that ZP3 alpha probably functions as a zona receptor for boar sperm and that carbohydrate has an important role in maintaining the functional integrity of the ZP3 alpha glycoprotein. PMID- 2590718 TI - Cell-mediated immune responses to sperm antigens: effects on mouse sperm and embryos. AB - Sperm antigens were assessed for their ability to induce cell-mediated immune (CMI) responses. Purified fertilization antigen (FA-1), protamine, and the lithium diiodosalicylate (LIS)-solubilized sperm preparation activated presensitized lymphocytes to secrete soluble mediators that activated macrophages and significantly inhibited sperm motility and embryonic development. The FA-1, however, was the most potent antigen in inducing proliferative response as well as the release of soluble mediators. LIS-sperm preparation, which contained numerous antigens, showed the least activity. The unsensitized control spleen cells did not secrete any factor(s) when activated with the antigen. In conclusion, these results indicate that sperm antigens can specifically induce (CMI) factors that have detrimental effects on sperm motility and preimplantation embryos. These findings may have potential clinical implications for humans, especially in immunologic and unexplained infertility, recurrent abortions, and development of antisperm contraceptive vaccines. PMID- 2590719 TI - Sexual skin in rodents: an across body region, gender, and species analysis. AB - The effect of estrogen on the thickness of skin layers were examined in male and female mice and in female rats. Skin samples were taken from prepubertally castrated subjects given either 17 beta-estradiol or control implants. In agreement with an earlier report, the subcutaneous areolar tissue (SAT) of the lower back was nearly six times thicker, on average, in female mice with estradiol implants than in controls. Estrogen did not effect the thickness of the epidermis or dermis but preferentially increased the thickness of the deepest layer of the SAT. Analysis of skin samples from different body regions revealed that this response to estrogen was limited to the skin of the dorsum and was greatest in the area of the lower back. Castrated male mice with estradiol implants had markedly thicker SAT layers in the lower back region than controls. However, the magnitude of the response was less than that seen in estrogen treated females. In contrast, the SAT in the lower back regions of castrated female rats with estrogen implants was not significantly different from controls, despite a pronounced uterine response to the hormone treatment. Thus, mice exhibit a species-specific, localized hypertrophy of one of the skin layers in response to estradiol. Mouse mating behavior involves the vigorous grasping and biting of the lower back region of the female. We suggest that at least one function of this estrogen-dependent hypertrophy is to protect the female from injury during mating. PMID- 2590720 TI - The source of Campylobacter pylori. AB - Sera from 98 abattoir workers were tested for IgG as well as for IgA to Campylobacter pylori, C. jejuni and Klebsiella. Clerical workers had significantly lower C. pylori and C. jejuni antibody levels than any of the groups in direct contact with freshly cut animal parts. No difference was found for antibodies to Klebsiella. Twenty-nine non-clerical workers with high IgG antibody levels against C. pylori consented to upper gastrointestinal endoscopy. C. pylori associated gastritis was found in all 29, and 4 weeks of colloidal bismuth subcitrate (240 mg/twice daily) was prescribed. On repeat testing at 3 months, all showed a decrease in IgG antibody levels to C. pylori but not to C. jejuni, whereas 18 untreated non-endoscoped workers showed no change. These findings raise the possibility that C. pylori infection is a zoonosis. PMID- 2590722 TI - A transient voltage-dependent outward current in cultured cerebellar granules. AB - Granule cells were dissociated from rat cerebella with a procedure that yields a 98% pure cell population. Potassium currents in these cells were studied using the patch-clamp technique. Depolarizing pulses of 10 mV step and 100 ms duration from a holding potential of -80 mV elicited two different potassium outward currents: a transient, low-voltage activated component and a long lasting, high voltage activated component. At +30 mV, the total current reached an amplitude of 2 nA (mean value of 15 experiments). The reversal potential of the transient current, estimated by measuring tail currents, was -77 mV, close to that predicted by the Nernst equation. The transient current was half inactivated with a holding potential of -78 mV and completely inactivated with -50 mV or more positive holding potentials. Finally, the current decay could be fitted by the sum of two exponentials with time constants of about 20 and 250 ms. PMID- 2590721 TI - Toxicity of HPA-23 (ammonium-21-tungsto-9-antimoniate) for normal human myeloid progenitor cells (GM-CFU) in vitro. AB - HPA-23 is a competitive inhibitor of the RNA-dependent DNA polymerase (reverse transcriptase) of the human immunodeficiency virus (HIV). It may therefore potentially benefit patients with HIV infection. This study aimed at defining the haematopoietic toxicity of this drug and particularly its effects on the normal human granulocyte-macrophage progenitor cells (GM-CFU). Our in vitro studies, in semi-solid agar, have shown an inhibitory effect of increasing concentrations of HPA-23 on colony and cluster formation. This effect is probably dose-dependent. An almost complete inhibition of colony formation was observed at doses of more than 20 micrograms/ml. Regarding cluster formation, a similar although much more progressive inhibitory effect was found. Our experimental data should be extrapolated with caution to clinical situations. However, they must be kept in mind for optimal design of HPA-23 therapy in HIV infected patients. PMID- 2590723 TI - Analysis by simulation of the transient rectification in molluscan neurons. AB - Central neurons of Lymnaea stagnalis exhibit, by the dne of a hyperpolarizing current pulse, a breaking-off of the rise of the membrane potential to the resting level. By using an electrical model of the membrane, this effect is accounted for by the activation of the fast outward current. PMID- 2590724 TI - Motor responses of Halobacterium halobrium to sinusodial light stimuli. AB - Sinusoidal light stimuli have been used to elicit photoresponses in Halobacterium halobium at various periods of the stimulus. Cycle histograms and histograms of the times between consecutive reversals are used to illustrate the responses, and the method used to obtain sinusoidally modulated intense light (with periods up to 1 s) is described. PMID- 2590725 TI - Ca2+ interaction with phospholipid bilayers studied by multifrequency phase fluorometry. AB - Calcium interaction with phospholipid membranes containing phosphatidic acid is studied by multifrequency phase fluorometry, using DPH as fluorescent molecule. DPH decay is analysed by a continuous distribution of lifetimes. The results suggest an increase of membrane heterogeneity at low calcium concentrations, without changes in the polarity of the environment surrounding the probe. PMID- 2590726 TI - High performance liquid chromatographic analysis of time-dependent changes in urinary excretion of indoleamines following tryptophan administration. AB - Analytical conditions of prepurification extraction and HPLC separation were optimized for determination of urinary serotonin and tryptamine. Under optimal conditions, serotonin, tryptamine and an internal standard were extracted with 15% v/v n-propanol in diethyl ether from urine samples alkalized with a phosphate buffer (0.75 mol/L, pH 10.0), and then they were re-extracted into an HCl solution (0.1 mol/L). Purified indoleamines were simultaneously separated by reversed-phase ion-pair HPLC with native fluorescence detection. Urinary serotonin and tryptamine were selectively determined within about 45 min per sample for the whole procedure. Analytical recovery, reproducibility and detection sensitivity were satisfactory for pursuing time-dependent changes in indoleamine levels. Urinary excretion profiles of serotonin and tryptamine in subjects dosed with L-tryptophan were successfully analyzed by our method. PMID- 2590727 TI - Determination of total and free concentration of propranolol in human plasma by displacement electrophoresis in a two-layer polyacrylamide gel using fluorimetric detection. AB - A new method based on displacement electrophoresis has been developed for the determination of the total and free concentration of propranolol, a beta adrenergic blocker drug, in plasma. To determine the total concentration the drug is extracted from human plasma into a chloroform + heptane mixture in the presence of ammonia. After evaporation of the solvent mixture the residue is submitted to displacement electrophoresis in a glass tube containing a two-layer polyacrylamide gel. When the propranolol electrophoretically leaves the gel column it is transferred by a buffer flow to the cuvette of a fluorimeter for continuous detection and quantification. The concentration of the free non protein bound drug can be determined by the same displacement electrophoresis technique following extraction of the plasma sample into the above organic solvent mixture in the absence of ammonia. Alternatively the extraction procedure can be exchanged for dialysis for 1 h. To decrease the risk that large size material might comigrate with propranolol two layers of polyacrylamide are used, one having small pores to retard such material. In addition, we use fluorimetric detection which means that many possible contaminants are not recorded and therefore do not affect a quantitative determination of propranolol. PMID- 2590728 TI - Determination of thiols and disulfides in normal rat tissues and hamster pancreas treated with N-nitrosobis(2-oxopropyl)amine using 4-(aminosulfonyl)-7-fluoro 2,1,3-benzoxadiazole and ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate. AB - Biological thiols and disulfides in rat and hamster tissues were simultaneously determined by HPLC-fluorescence detection using 4-(aminosulfonyl)-7-fluoro-2,1,3 benzoxadiazole (ABD-F) and ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate (SBD-F). The coefficients of variation (CV) of the method for reduced glutathione (GSH) and oxidized glutathione (GSSG) in liver and for cysteine (CySH) and cystine (CySSCy) in kidney were less than 3.1%. In 11 tissues of Wistar rats (liver, spleen, heart, lung, stomach, bladder, ovary, uterus, adrenal, kidney and pancreas), only CySH, CySSCy, GSH and/or GSSG were detected. Other thiols and disulfides were at extremely low levels in all samples. Both concentrations of CySH and CySSCy in the livers of old rats (111 weeks old, F344) were significantly higher than those of young rats (8 weeks old) (CySH, 0.246 +/- 0.099 vs 0.130 +/- 0.020 mumol/g; CySSCy, 0.051 +/- 0.027 vs 0.013 +/- 0.002 mumol/g). Administration of N-nitrosobis(2-oxopropyl)amine (BOP), a selective carcinogen of hamster pancreatic cancer, to Syrian golden hamsters (38 weeks old) resulted in the increase in the pancreas of GSH to a level 19 times as high and of GSSG to a level 14 times as high as those in untreated hamsters (GSH, 1.173 +/ 0.272 vs 0.062 +/- 0.017 mumol/g; GSSG, 0.155 +/- 0.063 vs 0.011 +/- 0.001 mumol/g). PMID- 2590729 TI - Quantitative determination of itazigrel in rodent diet by reversed-phase HPLC and evaluation of its stability at 20 degrees C. AB - A simple, accurate and precise procedure for the quantitation of itazigrel (a potent lipophilic inhibitor of collagen and arachidonic acid-induced aggregation being studied for its effects on peripheral vascular disease) from granulated rodent diet is presented. The drug was extracted from rodent diet using methanol + water (80:20) following dissolution of the diet in water. Samples of the supernatant were injected into the HPLC and the eluent was monitored with a fluorescent detector (lambda ex = 320 and lambda em = 430) to achieve analytical specificity. Interday coefficients of variation of the calibration curve slope were +/- 6% on standards between 0 and 1000 micrograms/g. Potency and homogeneity of the drug spiked diet prepared over a 1 year interval at 70, 200 and 600 micrograms/g was 99.3 +/- 2.5%, 100 +/- 1.8%, and 101 +/- 1.9% of label, respectively. Samples prepared for chromatography were stable for 24 h at 20 degrees C, and drug in diet was stable for 102 days when protected from light and stored at 20 degrees C. PMID- 2590730 TI - Phagocytic activity of human colostrum macrophages. AB - 1. We evaluated the ability of human colostrum adhering cells to phagocytize sheep red blood cells (E) incubated with rabbit anti-E IgG antibody (A) and zymosan particles incubated with fresh human serum or with the aqueous phase of colostrum. 2. The cells were found to have considerably intense phagocytic ability, i.e., 96.8% phagocytized EA particles, 83.2% phagocytized zymosan particles opsonized with fresh human serum, and 73.3% phagocytized zymosan particles opsonized with the aqueous phase of colostrum. Thus, the aqueous phase of colostrum can opsonize zymosan particles, an activity attributed to the complement system. 3. Total hemolytic complement (CH50) and the C3 component in a pool of normal human serum were two-fold higher than in a pool of the aqueous phase of colostrum. 4. These results indicate the existence of Fc gamma and C3 receptors on the membrane of human colostrum macrophages and suggest that these cells may be biologically active. PMID- 2590731 TI - Effect of oral glucose on peripheral muscle fuel metabolism in fasted men. AB - 1. The metabolic adaptations of peripheral muscle during a 5-day "modified" fast (daily oral intake of 200 g of glucose) were studied in 12 normal males. The volunteers were studied initially after receiving a balanced 2,400-kcal diet for at least 3 days (S1) and then after 5 days of modified fast (S2). The forearm muscle exchange of energy substrate (glucose) and the carbohydrate and lipid oxidation rates in muscle were measured during the postabsorptive state (S1) and after an oral glucose challenge (S2). 2. Glucose intolerance was not observed in either situation. Arterial glucose levels increased from a basal value of 83 mg/100 ml to 171 mg/100 ml in S1 and to 187 mg/100 ml in S2 at 30 and 60 min, respectively, and returned to basal values at 180 min in both studies. Increased forearm glucose uptake was observed in S2 compared to S1 (121.7 +/- 17.1 vs 92.6 +/- 12.0 mg 100 ml forearm-1 3 h-1), with decreased glucose oxidation (23.8 +/- 3.7 vs 30.4 +/- 4.7 mg 100 ml forearm-1 3 h-1) and increased glucose storage (98.0 +/- 16.6 vs 62.2 +/- 10.8 mg 100 ml forearm-1 3 h-1) as muscle glycogen. 3. Basal serum free fatty acid (FFA) levels were significantly more elevated in S2 than S1 (1030 +/- 95 vs 657 +/- 59 mumol/l; P less than 0.05) but were markedly reduced by glucose ingestion in both studies (352 +/- 33 (S2) vs 364 +/- 30 (S1) mumol/l at 120 min). Basal FFA oxidation was similar in both studies (0.091 +/- 0.015 (S1) vs 0.105 +/- 0.019 (S2) mg 100 ml forearm-1 min-1) and decreased significantly 3 h after glucose ingestion only in S1 (0.030 +/- 0.010 (S1) vs 0.078 +/- 0.020 (S2) mg 100 ml forearm-1 min-1; P less than 0.05). 4. The insulin response to oral glucose was similar in both studies (11,060 +/- 899 (S1) vs 11,078 +/- 918 (S2) microU ml-1 3 h-1), but the peak concentration occurred later (60 min (S2) vs 30 min (S1] and basal levels were significantly lower in S2 compared to S1 (9.2 +/- 1.7 vs 11.1 +/- 1.5 microU/ml; P less than 0.05). 5. These data show that the metabolic adaptations of normal subjects to a 5-day "modified" fast (daily oral intake of 200 g glucose) were increased muscle uptake of glucose, with reduced glucose oxidation and increased glucose storage in the form of muscle glycogen. PMID- 2590732 TI - Do connective tissue components induce plasma activation in vivo? AB - 1. This paper describes the effect of homologous plasma in contact with connective tissue on vascular permeability, edema and cell migration. 2. The contact of "non-activated" plasma with connective tissue structures does not result in generation of mediators responsible for increase in vascular permeability or in edema. 3. "Activated" plasma is able to induce vascular permeability and edema when in contact with connective tissue components. 4. Injection of "non-activated" or "activated" plasma induced a mild inflammatory cell migration. PMID- 2590733 TI - Morphology and viability of the spleen after subtotal splenectomy. AB - 1. Postsplenectomy complications have stimulated surgeons to opt for partial splenectomy as a more desirable technique for several diseases and in some cases for trauma to the spleen. 2. We studied spleen viability in 15 dogs submitted to subtotal splenectomy while maintaining the upper pole and upper splenogastric vessels. Macro- and microscopic histological studies as well as Tc99m-labeled heat-damaged erythrocyte scintigraphic analysis of splenic blood irrigation were carried out. 3. We conclude that: a) the splenogastric vessels are sufficient for the maintenance of spleen irrigation and drainage; b) the spleen remnants develop increased cellularity of the splenic cords and lymphoid folliculi; c) the length of the spleen remnants does not change for at least 2 months after surgery. PMID- 2590734 TI - Immunization of equines with phospholipase A2 protects against the lethal effects of Crotalus durissus terrificus venom. AB - Equines (2 horses and 2 donkeys) immunized with whole Crotalus durissus terrificus venom or its phospholipase A2 component either presented an increased survival time determined 3 days after challenge or were totally resistant to a challenging lethal dose of 200 mg crude venom 270 days after the initial immunization or 90 days after the last booster injection. The resistance was demonstrable on the basis of a good correlation with antibody titers determined by the ELISA method but not with the flocculation and neutralization assays. Since phospholipase A2 is essentially nontoxic, it can be used as a substitute for whole venom for the production of commercial antisera and as an immunizing agent in prophylactic programs. PMID- 2590735 TI - Effects of acute volemic changes on jejunal compliance in dogs. AB - 1. Jejunal compliance (delta V/delta P) was calculated from the intraluminal pressures measured in anesthetized dogs in an in situ upper jejunal pouch (40-50 ml capacity) with intraluminal volumes of 10, 20, 30, 40 and 50 ml of isotonic saline. 2. Measurements were made in the same animal during and after acute and sequential alterations of the extracellular fluid (ECF) volume obtained by: a) acute intravenous (iv) infusion of isotonic saline, b) acute hemorrhage, and c) iv reinfusion of isotonic saline. 3. Expansion of the ECF volume caused a significant, reversible downward shift of the compliance curve, i.e., the jejunal pouch became less receptive to liquid distension. After saline infusion was discontinued, compliance gradually returned to control levels. 4. Acute loss of a substantial volume of blood after ECF expansion gradually shifted the compliance curve upwards to levels significantly different from control, indicating that retraction of the ECF volume made the jejunal pouch more receptive to liquid distension. 5. Reinfusion of bled animals with saline rather than autologous blood also induced a significant decrease in jejunal compliance to below control levels. 6. The jejunal pouch behaved as a suitable preparation for monitoring in vivo modifications of compliance induced by acute changes in ECF volume, especially when it was nearly "half-full" (i.e., filled with 20 ml), suggesting a critical relationship between the volume capacity of the pouch and its fluid content. 7. These results suggest that the modulation of the jejunal portion of small intestine compliance is involved in the processes that balance the ECF volume during acute life-threatening situations such as accidental hyperhydration or hemorrhage. PMID- 2590736 TI - Child health: one hundred years of progress and today's challenges. 1988 Annual Health Conference, the New York Academy of Medicine. PMID- 2590737 TI - Ending the reign of dogma: designing a child health policy for America. The Duncan W. Clark lecture. PMID- 2590738 TI - Early education. PMID- 2590739 TI - The school's role in achieving better health. PMID- 2590740 TI - Shaping humane values--popular media and much more. PMID- 2590741 TI - Problem behaviors and AIDS. PMID- 2590742 TI - The world of youth and work. PMID- 2590743 TI - The challenge of adolescent sexuality. PMID- 2590744 TI - Child and adolescent mental health: neurobiological and social knowledge and their application for children and families. PMID- 2590745 TI - Models of effective advocacy for children. PMID- 2590746 TI - Child health in New York City. PMID- 2590747 TI - Sources of support: the financial and political base for children's health care. PMID- 2590748 TI - Programs that succeed for the disadvantaged. PMID- 2590749 TI - Advocacy: linking the political forces to achieve program success. PMID- 2590750 TI - The future of information systems for the medical sciences. Proceedings of a symposium. April 25, 1988. PMID- 2590751 TI - The information explosion. PMID- 2590752 TI - Organizing and accessing the literature. PMID- 2590753 TI - Role of libraries in medical education. PMID- 2590754 TI - Anniversary discourse: the Office of the Chief Medical Examiner. PMID- 2590755 TI - Thoughts on the future of medicine. PMID- 2590757 TI - Statement on preservation of New York City's drinking water quality. Committee on Public Health. PMID- 2590756 TI - Will libraries exist in the year 2000? The effect of prices on collections. PMID- 2590758 TI - Current issues in clinical engineering and biomedical technology certification. PMID- 2590759 TI - The biomedical engineering technician as a member of the clinical research team. PMID- 2590760 TI - Managing equipment service contracts. PMID- 2590761 TI - Biomedical engineering fundamentals of the intra-aortic balloon pump. PMID- 2590762 TI - Anesthetic and respiratory gas measurements by infrared technology. AB - Infrared systems for measuring respiratory gas are accurate, stable, and reliable, and cover most respiratory gases. Their most serious limitations (requiring complementary analyzers) are their inabilities to measure O2 (to assure a safe inspired O2) and nitrogen (for clinical N2 washout and detection of air emboli). Properly designed IR systems can monitor higher breath rates, are smaller, require less power, and are less costly than time-shared mass spectrometers. IR systems have a multitude of interfering factors that affect absorption, but control and analysis systems can compensate for them. IR technology continues to advance, with its most recent enhancement being the ability to identify the anesthetic agent in use. Mass spectrometers and Raman analyzers, which have more comprehensive capabilities, will not render IR technology obsolete until they can meet IR technology levels for cost, size, and reliability. PMID- 2590763 TI - Raman scattering for respiratory gas monitoring in the operating room: advantages, specifications, and future advances. PMID- 2590764 TI - An automated interferometer for the analysis of anesthetic gas mixtures. PMID- 2590765 TI - Anesthetic agent analysis using piezoelectric microbalance. PMID- 2590766 TI - Acoustic gas measurement. PMID- 2590767 TI - Give criticism that helps, doesn't hinder. PMID- 2590768 TI - Evidence for two P2-purinoceptor subtypes in human small pulmonary arteries. AB - 1. P2-purinoceptors have not been characterized in human pulmonary vessels and we therefore examined the effects of adenosine 5'-triphosphate (ATP) and its analogues on human isolated small pulmonary arteries (SPA) in vitro. 2. Contractile responses were induced by all of the analogues, with the rank order of potency alpha,beta-methylene-ATP (alpha,beta-meATP) = beta,gamma-methylene-ATP (beta,gamma-meATP) greater than ATP greater than 2-methylthio-ATP, indicating the presence of vasoconstrictor P2x receptors. 3. In precontracted SPA, vasodilator responses were produced by all of the analogues. The rank order of potency for the analogues causing vasodilator responses was: 2-methylthio-ATP much greater than ATP much greater than beta,gamma-meATP = alpha,beta-meATP, indicating a vasodilator P2y receptor. 4. Removal of endothelial cells had no significant effect on either the contractile or relaxant responses to any of the analogues. 5. After pretreatment of the endothelium-denuded vessels with alpha,beta-meATP (to desensitize P2x receptors), the contractile response to beta,gamma-meATP (a potent P2x receptor agonist) was abolished. 6. We conclude that both P2x- and P2y purinoceptors are present in human SPA and that both receptors reside on the vascular smooth muscle. PMID- 2590769 TI - Amelioration of glycerol-induced acute renal failure in the rat with 8 cyclopentyl-1,3-dipropylxanthine. AB - 1. Previous studies have shown that 8-phenyltheophylline (8-PT), a non-selective antagonist at adenosine A1- and A2-receptors, can ameliorate the severity of glycerol-induced acute renal failure (ARF) in the rat. In the present study we have examined the effects of an antagonist with selectivity for adenosine A1 receptors (8-cyclopentyl-1,3-dipropylxanthine, CPX) on the development of ARF. 2. In the anaesthetised rat 8-PT (4 mg kg-1, i.v.) and CPX (0.1 mg kg-1, i.v.) antagonised adenosine-evoked responses which are thought to be mediated via A1 receptors (bradycardia and decrease in renal blood flow). The agonist dose-ratio produced by CPX was equal to or greater than that found with 8-PT (heart rate and renal blood flow respectively). The hypotensive response to adenosine which is predominantly due to A2-receptor activation was also antagonised by 8-PT, whereas CPX was a much less effective antagonist of this response. 3. Administration of CPX (0.1 mg kg-1, i.v.; twice daily for two days) significantly attenuated the increase in plasma levels of urea and creatinine, the increased kidney weight and the renal tubule damage observed in rats 2 days following induction of ARF with intramuscular glycerol injection. In addition treatment with CPX significantly enhanced the clearances of inulin and p-aminohippurate. 4. After glycerol injection, the mortality rate over 7 days in untreated and vehicle-treated rats was 43% and 21% respectively. In contrast, all animals treated with CPX survived over the 7 day observation period. 5. These results support the suggestion that adenosine is an important factor in the development of ARF and indicate that this effect of the purine is likely to be mediated via an adenosine A1-receptor. PMID- 2590770 TI - Protein kinase C regulates the tonic but not the phasic component of contraction in guinea-pig ileum. AB - 1. We have investigated the effect of phorbol esters and the down-regulation of protein kinase C on contraction of guinea-pig ileum longitudinal smooth muscle to carbachol and high K+. 2. Phorbol 12,13-dibutyrate (PDBu) enhanced the phasic component and inhibited or enhanced, respectively, the tonic component of contraction to carbachol and high K+. In contrast, 4 alpha-phorbol, which does not activate protein kinase C, had no effect on these responses. 3. Exposure to phorbol 12-myristate 13-acetate (PMA; 1 microM) for up to 8 h induced a time dependent loss of [3H]-PDBu binding sites, consistent with the down-regulation of protein kinase C by this treatment. 4. The phasic component of contraction to carbachol or high K+ was unaffected following the down-regulation of protein kinase C. The tonic component of contraction to carbachol was markedly enhanced by this treatment while that to high K+ was partially suppressed. 5. These data suggest that although the activation of protein kinase C can lead to potentiation of the phasic component of contraction to carbachol or high K+, this appears to have little physiological significance since the response is not altered in tissues in which protein kinase C has been down-regulated. On the other hand, protein kinase C may limit the tonic contraction to carbachol but potentiate that to high K+. PMID- 2590771 TI - Relations between structure and nicotine-like activity: X-ray crystal structure analysis of (-)-cytisine and (-)-lobeline hydrochloride and a comparison with (-) nicotine and other nicotine-like compounds. AB - 1. Although (-)-cytisine is a rigid structure, it occurs in the crystal in two distinct but very similar conformations in which the pyridone ring is tilted relative to the charged nitrogen atom at much the same angle as the pyridine ring is in (-)-nicotine hydrogen iodide. The carbonyl group in the pyridone ring of ( )-cytisine, however, is on the side of the ring opposite to pyridine nitrogen in (-)-nicotine. 2. The pKa of (-)-lobeline HCl at 25 degrees C is 8.6 (approx), indicating that (-)-lobeline is at least 90% in the protonated form at physiological pH (7.6). It is probably the phenyl 2-keto-ethyl part of (-) lobeline, rather than the phenyl 2-hydroxy-ethyl part, which interacts with the receptor. 3. The combination within one molecule of a charged ('onium') nitrogen atom lying out of the plane of, and some distance (4.5-6.5 A) from, an aromatic ring is common to many compounds with nicotine-like activity (e.g. nicotine, cytisine, choline phenyl ether bromide, dimethyl-phenyl-piperazinium (DMPP) iodide, coryneine iodide and m-hydroxyphenylpropyl trimethyl ammonium iodide). In some molecules the aromatic ring can be replaced by an unsaturated group, such as carbonyl (e.g. acetylcholine) or double-bonds (e.g. anatoxin). 4. Activity at nicotinic receptors appears to involve interactions between the positively charged nitrogen atom and a negatively charged group, probably close to cysteine residues 192 and 193 in the receptor. It is suggested that rather than specific groups in the molecule also being involved, activity at nicotinic receptors depends on interactions between a flat part of the drug containing double-bonds, or systems of double bonds, and a planar area in the receptor, possibly tyrosine or phenylalanine residues. PMID- 2590772 TI - Properties of the cromakalim-induced potassium conductance in smooth muscle cells isolated from the rabbit portal vein. AB - 1. Single smooth muscle cells were isolated freshly from the rabbit portal vein and membrane currents were recorded by the whole-cell or excised patch configurations of the patch-clamp technique at room temperature. 2. Cromakalim (Ckm, 10 microM) induced a potassium current (ICkm) that showed no pronounced voltage-dependence and had low current noise. 3. This current, ICkm, was inhibited by (in order of potency): phencyclidine greater than quinidine greater than 4-aminopyridine greater than tetraethylammonium ions (TEA). These drugs inhibited the delayed rectifier current, IdK, which is activated by depolarization of the cell, with the same order of potency. 4. Large conductance calcium-activated potassium channels (LKCa) in isolated membrane patches were blocked by (in order of potency) quinidine greater than TEA approximately phencyclidine. 4-Aminopyridine was ineffective. A similar order of potency was found for block of spontaneous transient outward currents thought to represent bursts of openings of LKCa channels. 5. The low current noise of ICkm at positive potentials, and its susceptibility to inhibitors indicated that it was not carried by LKCa channels, and that it may be carried by channels which underlie IdK. It was observed that when ICkm was activated, IdK was reduced. However, in two experiments, ICkm was much more susceptible to glibenclamide than IdK; possible reasons for this are discussed. PMID- 2590773 TI - In favour of the vesicular hypothesis: neurochemical evidence that vesamicol (AH5183) inhibits stimulation-evoked release of acetylcholine from neuromuscular junction. AB - 1. The effects of optical isomers of vesamicol (2-(4-phenylpiperidino) cyclohexanol), an inhibitor of acetylcholine (ACh) storage, on stimulation-evoked release of [3H]-acetylcholine [( 3H]-ACh) from the neuromuscular junction have been studied in the region of the mouse hemidiaphragm which contains the motor endplates, and which can easily be loaded with [3H]-choline. This method made it possible to detect exclusively the Cao-dependent release of [3H]-ACh in response to stimulation, and therefore to test the vesicular hypothesis. 2. (-)-Vesamicol was approximately 20 times more potent than (+)-vesamicol in reducing stimulation evoked release of [3H]-ACh. 3. 4-Aminopyridine, a potassium channel blocker, enhanced the release of ACh in response to stimulation, but failed to increase release from hemidiaphragm which had been pretreated with (-)-vesamicol. 4. The fact that (-)-vesamicol inhibited the release of [3H]-ACh in response to electrical stimulation only when it was administered prior to the loading of the tissue with [3H]-choline, and had no effect when the stores had already been filled with labelled [3H]-ACh indicates that the stimulation-evoked release of [3H]-ACh is of vesicular origin and (-)-vesamicol has no effect on the release process. This is the first neurochemical evidence for the vesicular origin of stimulation-evoked release of ACh from the neuromuscular junction. PMID- 2590774 TI - Effects of hypoxia, elevated K+ and acidosis on the potency of verapamil, diltiazem and nifedipine in the guinea-pig isolated papillary muscle. AB - 1 The effects of the structurally diverse calcium channel blockers verapamil, nifedipine and diltiazem were investigated on the force of contraction of guinea pig, electrically stimulated papillary muscles in vitro. 2 Calcium channel blocking potency was assessed either as a direct negative inotropic effect or as the ability of the drugs to antagonise the positive inotropic effects of added calcium (Ca2+). By either method, the rank order of potency was found to be nifedipine greater than verapamil greater than diltiazem. 3 Various factors which mimic some of the consequences of acute ischaemia in vivo, namely low pH, hypoxia and elevated K+, in combination, but not singly, enhanced the negative inotropic potency of verapamil and to lesser extent that of diltiazem, but not that of nifedipine. 4 Whilst the various interventions, especially in combination, produced a profound negative inotropic effect themselves, this was not responsible per se for the potentiation of the negative inotropic effects of verapamil and diltiazem, since the negative inotropic effects of nifedipine and dinitrophenol were not potentiated under the 'ischaemic' conditions. 5 By use of antagonism of the positive inotropic action of exogenous Ca2+ as an alternative measure of potency, the differential influence of 'ischaemia' on calcium channel blocker potency was confirmed. The effect of verapamil was potentiated some 9 fold, that of diltiazem about 2 fold, and that of nifedipine was unchanged. 6 The differential effect of 'ischaemia' on the potencies of the calcium channel blockers was unexpected. Verapamil (but not nifedipine) is thought to bind to the calcium channel at a specific site not easily accessible from the extracellular space. 'Ischaemic' conditions may cause membranal perturbations which allow verapamil easier access to its binding site thus increasing its negative inotropic potency. PMID- 2590776 TI - The varieties of human experience. AB - The basic unit of study for psychiatric investigation is the individual human being in interaction with the environment. The psychological understanding of human biography provided by psychodynamic observation is now being supplemented by knowledge derived from phenomenological and neurobiological research. Phenomenology and neurobiology are at present primarily concerned with detecting correlations between clinical syndromes and pathological brain states; they are static rather than dynamic in approach. However, currently emerging techniques of brain imaging aimed at elucidating neurophysiological processes provide the basis for going beyond structural neuropathology to neuropathophysiology. It is suggested that the observations derived from the psychodynamic study of patients constitute markers of underlying brain function, and that the future investigation of psychiatric illness must include a correlative study of both psychodynamic and neurobiological processes. PMID- 2590775 TI - Endothelium-dependent relaxation and hyperpolarization of canine coronary artery smooth muscles in relation to the electrogenic Na-K pump. AB - 1 In the smooth muscle cells of canine coronary artery, acetylcholine (ACh) produced a transient, endothelium-dependent hyperpolarization of the membrane. A similar hyperpolarization was also elicited by exposure to Krebs solution after incubation of the artery in K-free solution for 30 min. 2 A hyperpolarization of reproducible amplitude was generated when ACh was applied at intervals greater than 30 min. Repetitive application of ACh at 15 min intervals caused a successive reduction in the amplitude of hyperpolarization. 3 The reduction in the amplitude of relaxation during five successive applications of ACh at 15 min intervals was less than 10% of the first relaxation. 4 The ACh-induced hyperpolarization was blocked by atropine but not by ouabain, whereas the K-free induced hyperpolarization was blocked by ouabain. In low Na (Li-substituted) solution, ACh still induced a hyperpolarization but the K-free induced hyperpolarization was absent. 5 In coronary artery precontracted by high-K solution, ACh produced an endothelium-dependent relaxation, without membrane hyperpolarization. The associated relaxation was resistant to ouabain but sensitive to atropine. 6 It is concluded that in the canine coronary artery, the electrogenic Na-K pump does not contribute to the endothelium-dependent hyperpolarization or relaxation. The results are consistent with the release of two different inhibitory factors from the vascular endothelium. PMID- 2590778 TI - Family therapy influences on general adult psychiatry. AB - Case notes of all patients admitted from two adjacent catchment areas with a diagnosis of schizophrenia, schizoaffective disorder, or psychosis were examined for information concerning the patient's family. On average, case notes contained only 9-25% of the basic information looked for. Family trees were rarely drawn. A record was made of contact with families of only half the sample. It is suggested that information concerning families is not considered of major importance in the management of such cases. PMID- 2590777 TI - The classification of functional psychoses and its implications for prognosis. AB - One hundred and eighty-three patients suffering from functional psychoses were diagnosed according to ICD-8, RDC, and DSM-III criteria, and the concordance rates for the diagnoses compared. The heterogeneity of the diagnosis 'schizoaffective psychosis' as defined by these systems became clear. With respect to prognosis, the DSM-III diagnosis of schizophrenia was most closely related to poor outcome. Affective psychoses and schizoaffective psychoses, as well as DSM-III 'schizophreniform disorders', demonstrated a favourable prognosis. PMID- 2590779 TI - Social support and the outcome of major depression. AB - One hundred and fifty middle-aged and elderly adults with a diagnosis of major depression were assessed initially as in-patients, and were reinterviewed 6-32 months later. Both size of social network and subjective social support were significant predictors of depressive symptoms at follow-up, with baseline depression scores and other predictors of outcome status statistically controlled. Subjective social support was most strongly associated with major depression; this effect was significantly stronger for middle-aged than older adults, and for men than women. Differences in the effects of marital status, size of social network, and subjective social support also suggest the importance of distinguishing between involvement in and quality of interpersonal relationships. PMID- 2590780 TI - The Scottish First Episode Schizophrenia Study. VI. Computerised tomography brain scans in patients and controls. AB - This is the initial report of a prospective study by computerised tomography brain scan of first episode schizophrenia. Twenty-seven patients who met Research Diagnostic Criteria for schizophrenia were compared with volunteer controls on ventricular:brain ratio, sulcal:brain volume ratio, and the widths of third ventricle and Sylvian and interhemispheric fissures. The results provide evidence that sulcal enlargement, but not ventricular abnormalities, may be detected at first admission for schizophrenic illness, and are discussed in relation to findings from other studies. PMID- 2590781 TI - Psychiatric disorders among medical in-patients in an Indian hospital. AB - Psychiatric symptoms among medical in-patients in an Indian hospital were assessed: the SRQ was used as a screening instrument, and those with probable psychiatric disorders were given the PSE and MSE, for further, detailed assessment. The prevalence of psychiatric disorders was 34%, with a further 15% reporting distressing psychiatric symptoms only. The most frequent complaints were delirium and adjustment disorders. They were largely associated with connective tissue, as well as cardiovascular and endocrine, disorders, and were characterised by depression, worrying and irritability. The reliability of the SRQ varied with the cut-off score, which gave optimal specificity and sensitivity when set at 9. PMID- 2590782 TI - The psychiatrist in the obstetric unit. Establishing a liaison service. AB - The establishment and first 18 months of a psychiatric liaison service to a general hospital obstetric unit are described. The service was initially intended to predict antenatally those at risk of post-natal depression and to offer follow up throughout pregnancy and in the post-natal period. However, a large proportion of referrals were of women currently unwell. Furthermore, post-natal follow-up in the community proved difficult. Referrals, diagnoses and disposal are analysed, leading to conclusions about the effectiveness and problem of such a service. The components of a comprehensive obstetric liaison provision are proposed, emphasising the need for strong community links built around a CPN service, allowing adequate postnatal psychiatric care. PMID- 2590783 TI - Psychological aspects of hysterectomy. A prospective study. AB - Sixty women aged between 30 and 55 years, having hysterectomy for benign conditions, were prospectively studied to investigate psychological adjustment to operation, and to explore social, psychological and physical factors associated with psychological outcome. A further 30 women were included for prospective research on psychological outcome. Investigations took place within two weeks of operation and after four months and 14 months. The findings indicated a high prevalence of pre-operative psychological morbidity (55%), which reduced to 31.7% afterwards. There was no evidence that hysterectomy led to a greater psychological distress. The principal risk factors of poor psychological outcome were the previous scores on the mental health measures and personality inventory. Involvement in the research process did not appear to affect psychological outcome. PMID- 2590784 TI - Significance of extreme temperament in infancy for clinical status in pre-school years. I: Value of extreme temperament at 4-8 months for predicting diagnosis at 4.7 years. AB - The relationship between extreme temperament in infancy and clinical status at 4.7 years of age was studied in temperamentally different groups of infants matched for sex and SES, and subselected from a large birth cohort representative of the general population. The effects of certain dimensions of family functioning and of other risk factors were examined. By itself, extremely difficult temperament in infancy had no strong direct association with clinical outcome at four years of age, whereas temperament assessed at four, family attitudes to discipline, and stressful events did. However, extreme temperament in infancy might indirectly affect outcome through its association with temperament at four. The interplay between adverse temperament and parental attitudes of discipline previously observed in middle childhood might have antecedents in pre-school years. PMID- 2590785 TI - Significance of extreme temperament in infancy for clinical status in pre-school years. II: Patterns of temperament change and implications for the appearance of disorders. AB - Few, if any, of children's behavioural or cognitive characteristics assessed in the first years of life demonstrate stability until later childhood; early characteristics have so far failed to show an association with future psychopathology. This longitudinal study, from 4-8 months to 4.7 years old, focused on stability and change of extreme temperamental traits in groups of infants subselected from a large birth cohort. Persistent extreme temperament at four and eight months old did not increase stability of temperament to four years of age, relative to other children in the whole population. Sizeable change occurred, and the environmental parameters associated with negative temperamental change did not seem to be the same as those related to positive change. Boys with extreme scores were more stable, while girls appeared more prone to positive change. It is hypothesised that the direction of temperamental change in the first years could be more meaningful for long-term prediction of disorders than any one assessment of temperament taken at any one year. PMID- 2590786 TI - Capgras' syndrome and folie a deux involving mother and child. AB - A mother and her son shared delusional beliefs that doubles of themselves existed and that they were being harassed by the police and social and educational services. The nature of these 'double double' symptoms is discussed. PMID- 2590787 TI - Epilepsy and arson. AB - A man temporarily developed an organic personality change, psychosis and epilepsy after a frontal lobe operation for a subarachnoid haemorrhage. While affected, he set fire to his house. The arson is thought to have been a direct result of a seizure. The case and its legal management are discussed. PMID- 2590788 TI - Altered state of consciousness in a compulsive water drinker. AB - A relatively normal 16-year-old Chinese woman with a six-month history of compulsive water drinking resulting in a comatose state is reported. The drinking was perpetuated by an enjoyable altered state of consciousness after ingestion of an average of 20 litres of water per day. Treatment by fluid restriction and, later, simple education was successful. The subjective dimension of an altered state of consciousness may provide an important explanation for the obscure aetiology. PMID- 2590789 TI - Psychotic illness following termination of pregnancy. AB - A case of a psychotic illness following an induced termination of pregnancy is described; this is discussed in relation to the literature on the subject, and possible aetiological factors in the case are reviewed. PMID- 2590791 TI - Zuclopenthixol-induced neuroleptic malignant syndrome at rechallenge and its extrapyramidal effects. AB - This is the first report of a zuclopenthixol-induced NMS. The lack of previous reports may be because the receptor-binding profile of thioxanthenes give rise to fewer extrapyramidal effects than comparable neuroleptics. It is important to know more of the relationship between the potential for induction of extrapyramidal effects and success in NMS rechallenge. PMID- 2590790 TI - The neuroleptic malignant syndrome and pneumomediastinum. AB - A patient is described who suffered from the neuroleptic malignant syndrome, complicated by a pneumomediastinum. This has not been reported previously. PMID- 2590793 TI - Defining personality disorder. PMID- 2590792 TI - The Camberwell Collaborative Depression Study. PMID- 2590794 TI - Positive symptoms of schizophrenia. PMID- 2590796 TI - Shoplifting in families of mentally handicapped persons. PMID- 2590795 TI - Delusion of inanimate doubles. PMID- 2590798 TI - Malignant hyperpyrexia syndrome in combined treatment. PMID- 2590797 TI - Hyperventilation causing asthma. PMID- 2590799 TI - The respectable art of modelling. PMID- 2590800 TI - Anti-type II collagen antibody in naturally occurring canine joint diseases. AB - Autoimmunity to collagen was investigated in several naturally occurring arthropathies of the dog. Increased levels of serum anti-native collagen type II antibody, as assessed by ELISA, were shown in 72.4% of dogs with rheumatoid arthritis (RA), 88% of dogs with infective arthritis (IA) and 52% of dogs with osteoarthritis (OA) (p less than 0.001). The mean levels of antibody in cruciate disease patients (CR) were also significantly increased compared to control dogs (p less than 0.01). Serum anti-collagen antibody in OA dogs correlated with that in precipitated serum immune complexes. There was also a correlation between anti collagen antibody level in synovial fluid and in synovial fluid complexes in dogs with rupture of the cranial cruciate ligament. In all patient groups, collagenase digestion of polyethylene glycol (PEG) precipitates from sera and synovial fluids caused a significant rise in specific antibody levels to collagen, indicating the presence of collagen-anti-collagen complexes in all arthropathies. In dogs with RA, the levels of collagen-specific antibody in synovial fluid complexes correlated with the total IgG in these complexes. These findings implicate collagen-anti-collagen complexes in the pathogenesis of naturally occurring joint diseases in the dog, but they are unlikely to be the primary aetiological mechanism. PMID- 2590801 TI - Evaluation of the Dutch Arthritis Impact Measurement Scales (DUTCH-AIMS) in patients with rheumatoid arthritis. AB - The Arthritis Impact Measurement Scales (AIMS) have been used to measure health status in patients with rheumatic diseases in North America. In this study, a Dutch version of this self-assessment questionnaire named the DUTCH-AIMS was evaluated in 73 Dutch patients with rheumatoid arthritis. Significant correlations between scores from the DUTCH-AIMS on the one hand and ARA functional class, haemoglobin, erythrocyte sedimentation rate, self-assessments of functional impairment and perceived overall health on the other hand indicate that the scales are valid and provide good estimations of various components of the health status of the Dutch arthritic patient. PMID- 2590802 TI - Effects of aerobic conditioning in lupus fatigue: a pilot study. AB - Fatigue, a complex symptom, significantly affects the quality of life in many patients with systemic lupus erythematosus (SLE). To understand this phenomenon, 23 patients with SLE and fatigue were studied. Standardized tests of depression (NIMH), fatigue, exercise tolerance (ETT) on a bicycle ergometer, and SLE activity were obtained. At baseline, SLE patients had significantly lower maximum oxygen consumption (VO2 max) than normals (p less than 0.005). Adjusted for age and sex, SLE patients perform at 54% of their expected maximum VO2, which is similar to published data from patients with rheumatoid arthritis. Depression by NIMH was not correlated with VO2 max or length of time on ETT. Fatigue measured by Profile of Mood States (POMS) was correlated with ETT time (r = 0.476, p less than 0.025) and with VO2 max (r = -0.402, p less than 0.07). After an 8-week aerobic conditioning programme the experimental group increased their aerobic capacity by 19% in contrast to 8% in controls. This change correlated with decreased fatigue as measured by visual analogue scales. Exercise did not exacerbate disease, and only two of 16 experimental subjects experienced transient joint symptoms during exercise. PMID- 2590803 TI - An excellent general practitioner telephones for advice. He has a 79-year-old male patient who has been blind (secondary to retinitis pigmentosa) since the age of 40, and who is moving to another city in one month's time. PMID- 2590805 TI - A patient recently presented with severe xerostomia and positive Schirmer's test 4 years after the onset of her rheumatoid arthritis. The diagnosis of secondary Sjogren's syndrome was made. PMID- 2590804 TI - The automatic assessment of knee radiographs in osteoarthritis using digital image analysis. AB - We have developed an automatic system for the measurement of joint space in the knee using computerized analysis of digital stored images of knee radiographs. PA X-rays of the knee are positioned on a conventional viewing box. A video image of the radiograph is converted to digital form, stored and displayed on a closed circuit television monitor. This is edited and analysed by a microcomputer. After careful positioning under a computer generated grid on the television screen, automatic measurements are made using an edge detection facility. Two different edge detection algorithms were compared. Reproducibility is very good. Inter- and intra-observer relationships are also good with no significant difference between observers using a paired t-test and very good correlations. Results show that rapid, reliable and accurate measurement of joint space size can be achieved using digital image analysis. The application of image handling computers to radiological scoring is important in our understanding of joint destruction and the progression of the rheumatic diseases. PMID- 2590806 TI - Sjogren's syndrome: association with type-1 diabetes mellitus. AB - This study of 102 unselected type-1 diabetic patients has shown that sicca symptoms affect 55% of the patients, although sometimes only during hyperglycaemic phases. While these symptoms might be attributable to the diabetes, the frequency of antinuclear antibodies in those suspected of having Sjogren's (25% by HEp-2) and particularly anti-Ro antibodies (32% by ELISA) reinforces the suspicion that Sjogren's syndrome may underlie their presence. PMID- 2590807 TI - Successful treatment of juvenile chronic arthritis with a specific antiviral agent. AB - In a previous paper we identified a group of patients with teenage onset chronic progressive arthritis (JCA or JRA) with raised antibody titres to influenza A (H2N2), an epidemic of which was present in the year they were born. On the basis that they might be chronic carriers of influenza A, and that this might be related to their arthropathy, it was decided to use the anti-influenza A drug amantadine to treat the virus and observe whether there was any effect on the joint disease. A 4-month, double-blind, placebo-controlled trial followed by a 4 month open study showed that amantadine could under these circumstances be of considerable therapeutic benefit while having no effect on patients without elevated antibody titres against influenza A. PMID- 2590809 TI - The synovial lining--a movable feast. PMID- 2590808 TI - Hypouricaemia with acute viral hepatitis. AB - We report five female cases of hypouricaemia accompanied by acute viral hepatitis (serum urate 101 +/- 12 mumol/l, mean +/- SD). Their urate clearance was increased to 14.2 +/- 3.4 ml/min during hyperbilirubinaemia but 24-h urate excretion was not elevated (2.09 +/- 0.64 mmol/24 h). No other renal tubular abnormalities were detected. Comparing urate metabolism with that of four cases of inborn renal hypouricaemia, the degree of uricosuria was lower. One patient showed elevation of serum and urinary oxypurine, which normalized with return of a normal blood uric acid level. In all cases, the serum urate returned to normal after improvement of liver function. We suggest that renal uricosuria due to an isolated renal defect of urate transport might contribute to hypouricaemia in these cases but that inhibition of xanthine oxidase activity might also contribute to this phenomenon. PMID- 2590810 TI - Tarsal tunnel syndrome in seronegative spondyloarthropathy. AB - A 53-year-old man affected by ankylosing spondylitis associated with psoriasis developed bilateral tarsal tunnel syndrome caused by synovitis of the accompanying sheaths of the tendons that run through the 'fibro-osseous tunnel'. This report confirms the hypothesis that the tarsal tunnel syndrome may be a clinical manifestation of seronegative spondyloarthropathy. PMID- 2590811 TI - Unilateral palsy of the hypoglossal nerve in a patient with tuberculosis of the first cervical vertebra. AB - A 26-year-old female developed a unilateral hypoglossal nerve palsy in association with tuberculosis of the first cervical vertebra. The extensive soft tissue and bony abnormalities were demonstrated only by computerized axial tomography. Involvement of the hypoglossal nerve within the skull by tuberculous granulation tissue was the most likely mechanism for the nerve palsy. PMID- 2590812 TI - Relative costs of antirheumatic drugs. PMID- 2590813 TI - Impact of NHS underfunding on rheumatology in-patient provision. PMID- 2590814 TI - Mixed membranous and proliferative glomerulonephritis in primary Sjogren's syndrome. PMID- 2590815 TI - Treatment with danazol for refractory thrombocytopenia in rheumatoid arthritis. PMID- 2590816 TI - Treatment of oesophagitis in scleroderma with omeprazole. PMID- 2590817 TI - Thermography in carpal tunnel syndrome (CTS) PMID- 2590818 TI - Lager louts--LAGER arthritis. PMID- 2590819 TI - Changes in pig salivary cortisol in response to transport simulation, food and water deprivation, and mixing. AB - Cortisol concentrations in the saliva of two groups (N = 5/group) of prepubertal pigs were measured by radioimmunoassay. Samples were collected in the home pen under normal husbandry conditions and after a 24 h period when food and water were withheld. The pigs were then transferred to a transport simulator, which was left stationary (control) or set in motion (experimental), and further samples were taken 1 h later before the animals returned to their pens. In the following week, the two groups of pigs were mixed and saliva was collected over a 3 h period. Samples were also taken 2 days later after the pigs had been injected with a maximally stimulating dose of adrenocorticotrophin (ACTH). Transport simulation in deprived animals, and mixing, produced salivary cortisol levels similar to those seen after ACTH. Food and water deprivation alone also increased cortisol secretion whereas transport simulation in non-deprived animals had no effect. These results indicate that salivary cortisol estimation offers a non invasive means of measuring stress responses in unrestrained pigs. PMID- 2590820 TI - The clearance of bromosulphthalein from plasma as a measure of the changes in hepatic function during pregnancy and lactation in ewes. AB - Single intravenous injections of bromosulphthalein (BSP) were given to sheep and the change in plasma BSP concentration with time was analysed by computer to obtain the proportionality transfer constants 'a', 'h' and 'b' and plasma volume. The BSP half-time, fractional clearance and retention values were also calculated. Alterations in BSP clearance were compared with changes in bilirubin and liver specific enzyme activities in ewes in late pregnancy and early lactation. The measurement of BSP clearance, particularly the proportionality transfer constants, yielded more information about the alterations in hepatocellular function during pregnancy and lactation than the changes in clinical chemistry. It is suggested that these alterations in liver function are physiological rather than pathological at these times. PMID- 2590821 TI - Adrenal response in the calf to repeated simulated transport. AB - The adrenal responses in calves submitted to simulated transport on three occasions for 30 min were evaluated. Plasma adrenaline, cortisol and NEFA increased significantly during simulated transport but became less marked in successive trials. Haematological stress-related parameters (Hb, PCV) increased to the same extent on repeated exposure to simulated transport. Plasma noradrenaline, glucose and cholesterol values were unchanged throughout the study. PMID- 2590823 TI - Effects of exogenous urea infusion on glucose metabolism in acute heat stressed swamp buffaloes (Bubalus bubalis). AB - The effects of intravenous urea infusion on glucose turnover, glucose carbon recycling, glucose pool size and glucose clearance were studied in buffaloes kept in either normal ambient temperature or acute heat exposure. Heat stressed animals showed increases in glucose turnover rate, plasma glucose concentration and glucose clearance but decreased glucose carbon recycling. A marked reduction of glucose turnover and glucose clearance associated with increased plasma glucose concentration in heat stressed animals after urea infusion reflects under utilization of this compound. Mechanisms involved in glucose metabolism during urea infusion in buffaloes are discussed. PMID- 2590822 TI - Effects of dihydroheptaprenol on neutrophil functions in calves. AB - Microemulsified dihydroheptaprenol (DHP) was administered intramuscularly to clinically healthy calves at doses of 4, 6 and 8 mg/kg body weight. Marked increase of neutrophil counts was observed 0.5, 1 and 2 days after the injection at a dose of 6 mg/kg. Nitroblue tetrazolium reducing activity of neutrophils was also obviously enhanced 1, 2 and 3 days after DHP administration. Phagocytic killing of Staphylococcus aureus by neutrophils was further enhanced markedly 1, 2 and 3 days after the drug injection at 6 mg/kg. PMID- 2590824 TI - Pharmacokinetics of halofuginone in cattle. AB - The pharmacokinetics of the antitheilerial drug halofuginone were evaluated in healthy calves following oral administration, at a dose of 1.2 mg/kg body weight, repeated after 48 h. The maximum plasma concentration after the first dose ranged from 3.8 to 7.7 ng/ml (6.5 ng/ml, mean) and occurred at between 12 and 32 h (22 h, mean). After the second dose, the maximum plasma concentration was 4.8-8.6 ng/ml (7.2 ng/ml, mean) occurring between 12 and 32 h (17 h, mean). The apparent terminal elimination half-life ranged from 24.2 to 28.9 h with a harmonic mean of 27.3 h. No significant difference was found in the apparent volume of distribution and the body clearance between the values calculated after the first dose and the two doses. The results show that the concentrations which persist in plasma from 8 to 120 h are above the in-vitro concentration of halofuginone required to reduce by 50% the proportion of lymphoblastoid cells containing Theileria parva schizonts (EC50 = 3 ng/ml), but the maximum plasma concentrations are only about 46% of the in-vitro optimal effective concentration, EC80 (15 ng/ml). PMID- 2590825 TI - Antibiotic persistence and tolerance in the lactating sheep following a course of intramammary therapy. AB - The commercial use of sheep for the production of milk and milk products is attractive to farmers actively diversifying their dairy interests due to the impact of the quota system. As intensification of milking increases, flock sizes will enlarge and the incidence of ovine mastitis will inevitably increase. The pharmaceutical industry and the veterinary practitioner will be required to provide advice and data upon the performance of currently available bovine intramammary preparations for the sheep. This study produces evidence to confirm that one available bovine intramammary preparation, when infused into milking sheep, produced a withholding time approximately three times as long as that defined for the cow. Following a course of three infusions over a period of 24 hours after consecutive milkings, milk was not acceptable for human consumption or for the production of cheese and yoghurts until 136 hours following the final infusion. This situation is likely to be representative of that which will occur with other intramammary products used in the ovine species following infusion with bovine intramammary preparations. PMID- 2590826 TI - Ovine caesarean operations: a study of 137 field cases. AB - Under field conditions a 97.8% success rate was achieved for caesarean operations performed on ewes with live or freshly dead lambs present in utero. Where lambs were in moderate to advanced stages of autolysis and emphysema the survival rate of the dam was 57.1%. Neither the presence of a vaginal prolapse nor abortion appeared to have an influence on the survival rate of the ewe. Interference and trauma to the posterior reproductive tract prior to veterinary examination reduced the success rate of cases. Ewes with a history during gestation of a prolapsed vagina were 10 times more likely to require a caesarean operation to correct the dystocia than normal ewes. A range of haematological variables failed to give an accurate prognostic guide to the outcome of surgery. A caesarean operation is recommended in preference to euthanasia of a ewe that could have been considered a poor-risk surgical case. Fetotomy was not possible in cases where emphysematous lambs were present in utero. PMID- 2590828 TI - Observations on bovine pyelonephritis. AB - Fifty-one cases of bovine pyelonephritis were investigated. The annual prevalence rate for 2089 cows was 1.6% in 1987 with a mean interval from calving to onset of cases of 82.9 days. Multipara were at higher risk. Loss from pyelonephritis was 33.3% of all affected cows, and relapse occurred in 9.4% of apparently recovered animals. Serum creatinine and urea concentrations were of high prognostic values. Odds ratios being culled for cows with levels of creatinine above 1.5 mg/dl (132.6 mumol/l) and of urea above 100.0 mg/dl (16.7 mmol/l) were 104.0 and 60.0 respectively compared with those with lower values. Haematological results were of no diagnostic value. Odds ratio for cows with no post-parturient uterine diseases having pyelonephritis was 8.9 compared with infected cows treated at calving with antibiotics. PMID- 2590827 TI - Effect of levamisole on parenteral vaccines for swine dysentery. AB - Leucocyte migration-inhibition and humoral antibody responses (HAR) were demonstrated in swine immunized with particulate or soluble antigen of Treponema hyodysenteriae. Levamisole (at the recommended deworming level), given simultaneously with particulate vaccine did not significantly (P greater than 0.05) enhance nor suppress the leucocyte migration-inhibition response. However, an enhancing leucocyte migration-inhibition of the drug was seen in pigs given soluble vaccine in combination with levamisole compared with those receiving soluble antigen alone. Levamisole generally suppressed the HAR throughout the immunization schedule of pigs given soluble or particulate vaccine. There was no significant suppression (P greater than 0.05) of clinical signs of swine dysentery (SD) in animals given particulate vaccine nor in those receiving this vaccine plus levamisole. However, pigs receiving soluble vaccine plus levamisole had fewer clinical signs of SD as well as significantly (P less than 0.05) fewer shedding episodes of T. hyodysenteriae than those given soluble antigen alone. When compared with the control pigs, swine vaccinated with soluble antigen had fewer days of total diarrhoea and shedding episodes of T. hyodysenteriae. However, the diarrhoea of vaccinated pigs was not significantly (P greater than 0.05) delayed when compared to the unvaccinated swine. PMID- 2590830 TI - Spinocerebellar tract neurons with axons passing through the inferior or superior cerebellar peduncles. A retrograde horseradish peroxidase study in rats. AB - Using the retrograde horseradish peroxidase (HRP) method, we determined whether axons of the spinocerebellar tract (SCT) neurons pass through the superior (SCP) or the inferior (ICP) cerebellar peduncle in rats. Following bilateral section of either the SCPs or the ICPs, HRP was injected into the cerebellar anterior lobe and lobule VI, and the resulting labeled neurons were quantitatively examined throughout the length of the spinal cord. Almost all SCT neurons in the central cervical nucleus, Clarke's column and lamina VII of the third cervical (C3) to third thoracic (T3) segments and the T11 to fifth lumbar (L5) segments, and the majority of SCT neurons in the ventrolateral part of the anterior horn of the L6 to caudal (Ca) segments and laminae V of the C8-L5 segments and VII of the L6-Ca segments project their axons through the ICPs. The majority of spinal border cells (T11-L5) and a large number of SCT neurons in lamina VII of the C3-T3, T11 L5 and L6-Ca segments project their axons through the SCPs. A nearly equal number of SCT neurons in lamina VIII (C1-L6) send axons through the SCPs or the ICPs. The proportion of SCT neurons projecting via the SCPs versus those projecting via the ICPs was approximately 1:5. PMID- 2590829 TI - Healing of dehorning wounds. AB - Open wound healing following dehorning using a wire saw was observed in 25 cattle aged between 1 and 5 years. Initially, there was a marked thickening of the scab over the wound as a ridge near the skin margin. A pale yellow to pink membrane then developed from the sides of the frontal sinus opening. Granulation tissue formed to fill the frontal sinus opening before healing by epithelization, followed by wound contraction. In some animals a bony horn stump projecting about 2-3 mm above the wound surface appeared which underwent osteosis; the dead bone gradually loosened and fell off during the healing process; histological sections revealed the presence of numerous osteoclasts lining the bone spicules. The presence of the frontal sinus and the stump of the horn processes left after dehorning are factors that make the healing of an open dehorning wound unique compared with other wounds. PMID- 2590831 TI - An appraisal of some lesioning methods applied to the posterior hypothalamus in rats. AB - The behavioral changes and histological damage to the brain of rats were examined following lesions of the midlateral posterior hypothalamic area (MLPHA) made by passing electrical current through a metal electrode or through a glass pipette containing hydrogen ion (HCl) or kainic acid. Control experiments included placement of pipettes containing saline and imposing the same current as used in kainic-acid-containing electrodes (sham). Subcutaneous injections of kainic acid assessed damage that may be attributed to general neuronal cytotoxicity or limbic seizures. The effect of diazepam on alleviating behavioral changes and structural damage in kainic-acid-injected rats was examined. The current used to inject kainic acid produced significant damage to both neurons and axons of passage at the injection site. Degeneration of nerve terminals following kainic acid injections in the MLPHA was widespread, not predictably reduced by diazepam premedication and differed in only minor details from degeneration induced by subcutaneous injections. PMID- 2590832 TI - Neurophysiological investigation of the pretectal nucleus lentiformis mesencephali in Rana pipiens. AB - Previous studies have demonstrated that the large-celled, optic pretectal nucleus lentiformis mesencephali (nLM) is essential for horizontal optokinetic nystagmus, yet little is known about its neurophysiology. In the present study, single-unit analysis of nLM utilized a large-field, patterned stimulus presented for 8 directions and 3 velocities of movement. All units localized in nLM were spontaneously active, motion sensitive, with response profiles that ranged from strongly directional and narrowly tuned to asymmetric and broadly tuned. Only about one-third of the units could be classified as directional, and no response bias for horizontal or temporal-to-nasal motion was observed. The majority of directional units showed greatest responsiveness at the lowest stimulus velocity, while the reverse occurred for many broadly tuned units. These low-velocity, highly directional units may be comparable to the 'retinal slip' neurons recently described in the large-celled pretectal nucleus of mammals. Directional information in the nLM of Rana pipiens thus appears to be represented in the activity of a large population of motion-sensitive units which includes both narrowly and broadly tuned individual response profiles. These results are consistent with the population-coding hypothesis recently advanced to account for directional coding in other sensorimotor systems, including primate motor cortex and superior colliculus. PMID- 2590834 TI - Quantitative comparison of the limits on visual spatial resolution set by the ganglion cell layer in twelve species of reef teleosts. AB - A diverse range of retinal specializations are examined in twelve species of reef teleosts and estimates of the spatial resolution of neurons within the ganglion cell layer calculated using Matthiessen's ratio. Upper limits of between 4 and 27 cycles per degree were found to facilitate acute vision into frontal and eccentric space, utilizing temporal and nasal area centralis, respectively. Upper limits of between 3 and 20 cycles per degree were found in horizontal areas of acute vision across the retinal meridian. These areas are thought to be used for panoramic vision and may, in one species, indicate the relative importance of this region in comparison to the temporal area centralis. Comparisons are made between ganglion cell acuity and other morphological and behavioural acuities calculated in previous studies. PMID- 2590833 TI - Early development of the olfactory and terminalis systems in baleen whales. AB - The development of the olfactory and terminalis systems was studied in tissue from eight embryonic and early fetal specimens belonging to three species of baleen whales. In contrast to toothed whales, baleen whales, particularly in these ontogenetic stages, are much less specialized in nasal organ morphology. The nasal cavity and peripheral olfactory system are well developed and do not show signs of reduction. However, as in toothed whales, there is no trace of a vomeronasal organ or nerve. The terminalis neuroblasts can already be distinguished from the olfactory material in the embryonic period, and they form compact masses medial and caudal to the developing olfactory bulb. As in most prenatal toothed whales, there are two large intrameningeal terminalis ganglia. These are connected with the telencephalic wall by central rootlets and with the septal mucosa by fiber bundles running through the level of the future cribriform plate. Clusters of terminalis neuroblasts also lie near the septal mucosa and along the peripheral terminalis fiber bundles. The functional implications of the olfactory and terminalis systems in whales are discussed. PMID- 2590835 TI - Projections from the sacculus to the cochlear nuclei in the Mongolian gerbil. AB - The projections of the saccule, an otolith end organ, to the cochlear nuclei were studied using both transganglionic transport and intracellular injection techniques. Labeled fibers and terminals were observed in the anterior and posterior portions of the ventral cochlear nucleus and the dorsal cochlear nucleus. Most terminals were present in the granule cell domain, especially in the subpeduncular corner between the anteroventral cochlear nucleus and the floccular peduncle of the cerebellum. It has been hypothesized that the cochlea in mammals may have developed phylogenetically from the saccule. The projections from the saccule to the cochlear nuclei were investigated in a mammalian species, the Mongolian gerbil, in an attempt to obtain initial information supporting or refuting this hypothesis. The presence of an otolith end organ projection to the cochlear nuclei in rodents should encourage comparative studies in additional aspects of the evolution of the auditory system. PMID- 2590836 TI - Sub/supraependymal axonal net in the brains of sharks and probable targets in parasynaptic relationship. AB - A sub/supraependymal system of varicose axons in the tectal midline ridge formation of shark brains is described. Lengths of axons and their terminals are seen freestanding in the cerebrospinal fluid (CSF) as well as in close contiguity with the large CSF-contacting and supraependymal mesencephalic trigeminal neurons of the midline ridge formation. The relationship of axonal varicosities and terminals to both CSF and supraependymal somata is such as to suggest a nonsynaptic association. This finding is discussed in the context of its utility in testing the concept of parasynaptic modulation in vertebrate brains. The topographical arrangement described is one in which the essential operational elements of parasynaptic activity can be identified in a neuronal assemblage whose functional association is known. PMID- 2590838 TI - Effect of amantadine on motility of reserpinized mice as a function of brain biogenic amines and mouse strains. AB - The effect of amantadine, reserpine or both on locomotor activity and whole brain content of selected biogenic amines and major metabolites was studied as a function of mouse strain. Successive administration of small dose regimens of reserpine, 0.2 mg/kg IP, did not alter motility from corresponding saline control. Administration of amantadine, 100 mg/kg, IP, prior to each of the reserpine treatments produced either stimulation of motor activity in the albino ICR and black C57BL/6 mice or caused inhibition from reserpine in the albino BALB/C and the brown CDF-1 mouse strains. This suggests a genotype strain sensitivity to the amantadine and reserpine interaction on the motor behavior of the mouse. The amantadine treatment did not alter brain dopamine concentration but increased its immediate acid metabolite, 3,4-dihydroxyphenylacetic acid, in the C57BL/6 mice as contrasted with reduction of the same in the BALB/C mouse strain. Both BALB/C and C57BL/6 mice showed changes in brain normetanephrine levels as a consequence of the pharmacologic intervention used which suggest catecholaminergic sensitivity. The only changes produced by the agents studied in brain serotonin or 5-hydroxyindoleacetic acid levels were confined to the BALB/C mouse strain. No changes occurred in brain levels of the compounds measured from corresponding controls in the CDF-1 mice. The results indicate differential sensitivity of the serotonergic and dopaminergic systems to drug-drug interaction studied which appears to be strain dependent. PMID- 2590837 TI - Prenatal terbutaline exposure in the rat: selective effects on development of noradrenergic projections to cerebellum. AB - Terbutaline, used in the treatment of premature labor and asthma, crosses the placenta and can stimulate beta 2-adrenergic receptors in the fetus. This study examines the effects of prenatal exposure to terbutaline (10 mg/kg SC on gestational days 17, 18 and 19) on the development of noradrenergic projections in brain regions of the fetal and neonatal rat, using synaptosomal uptake of [3H]norepinephrine as a marker for synaptogenesis. Although terbutaline exposure did not compromise body or brain region growth, uptake was adversely affected selectively in the cerebellum, a region which also displays close coupling of fetal beta 2-receptors to control of cell development near term. These results thus provide biochemical evidence that terbutaline may be a neurobehavioral teratogen. PMID- 2590840 TI - Immunocytochemical study of enkephalin-like cell bodies in the thalamus of the rat. AB - The distribution of enkephalin-like cell bodies in the thalamus of the rat was studied by means of intratissular injections of colchicine and using an indirect immunoperoxidase technique. The densest clusters of immunoreactive perikarya were observed in the nuclei geniculatum lateralis ventralis, medialis dorsalis, centralis lateralis, centralis medialis and anterior ventralis. Whereas the nuclei praetectalis lateralis, lateralis posterior, habenularis lateralis, parataenialis (its caudal part), parafascicularis, centrum medianum, reuniens and ventralis medialis had the lowest density. In other thalamic nuclei geniculatum mediale, paraventricularis and parataenialis (its rostral part) the density of enkephalin-like cell bodies was intermediate. These results suggest that the intratissular injection of colchicine is the better way of administration of the drug in order to study the distribution of peptidergic cell bodies in the mammalian CNS. The similarities and differences found in the distribution of enkephalinergic cell populations in the thalamus of different mammals are discussed. PMID- 2590839 TI - Behavioral and metabolic aspects of cimetidine-ethanol interaction. AB - The effect of cimetidine, an H2 histamine receptor blocker, on spontaneous locomotor activity and ethanol-produced narcosis was studied in the male mouse. The separate and combined effects of cimetidine, and histalog (betazol), an H2 histamine receptor agonist, on voluntary intake of diluted ethanol solution by the rat were also determined. The in vitro effect of cimetidine on rat liver alcohol and aldehyde dehydrogenase was assayed. Cimetidine treatment was associated with an initial moderate increase in locomotor activity which was increased significantly as a function of time. The central depressant action of ethanol, as measured by duration of ethanol-mediated narcosis, was decreased by pretreatment with a single dose of cimetidine. The drug did not alter voluntary drinking of ethanol by the rat but antagonized histalog-produced aversion to ethanol selection when administered prior to histalog. Cimetidine, 3 x 10(-3) M concentration, inhibited rat liver aldehyde dehydrogenase but not alcohol dehydrogenase in vitro. The results indicate cimetidine-ethanol interaction and suggest the implication of histamine in some of the ethanol-elicited responses studied. PMID- 2590841 TI - Electrophysiological evidences of a bidirectional communication between the locus coeruleus and the suprachiasmatic nucleus. AB - To assess a possible relation between the suprachiasmatic nucleus (SCN) and the locus coeruleus (LC), a study with evoked potentials was performed in the rat. An evoked potential was recorded in the SCN area after electrical stimulation of the LC. Also, an evoked potential was recorded in the LC after electrical stimulation of the SCN area. The results indicate specificity of the projecting regions and of the activated regions, suggesting the existence of a possible bidirectional communication between the LC and the SCN. The pathways possibly involved are discussed. PMID- 2590842 TI - Test of a criterion for selecting intracranial doses of angiotensin receptor blockers. AB - Investigators using intracerebroventricular (ICV) injections of competitive antagonists of angiotensin II (Ang II) to study thirst usually select doses sufficient to block drinking to IV Ang II. We questioned whether this test truly indicates the dose needed under physiological conditions when Ang II-induced hypertension, which inhibits thirst, is not present. Rats were prepared with chronic venous and ICV cannulas, plus femoral arterial cannulas in those used to measure arterial pressure. Captopril (100 mg/kg SC) was given before all experiments to block endogenous Ang II production. The test dose of Ang II, 50 ng/kg/min IV for 1 hr, increased water intake and arterial pressure. We selected an ICV dose of saralasin (Sar1Ala8Ang II), 4 micrograms bolus and 4 micrograms/hr for 75 min, that did not stimulate drinking itself and completely blocked drinking to IV Ang II. This dose of saralasin only partially (45%) reduced drinking to the same dose of Ang II IV when arterial pressure was lowered by giving the vasodilator diazoxide (15 mg/kg IV). Diazoxide itself did not stimulate drinking. These results support our concern that the criterion normally used to select ICV doses of Ang II antagonists probably underestimates the amount needed to inhibit angiotensinergic drinking in hypovolemic or hypotensive animals. PMID- 2590843 TI - Cardiorespiratory responses following electrical stimulation of caudal sites in the rat medulla. AB - A limited occipital craniotomy was conducted on urethane-anesthetized rats to expose the caudal medulla in the region of the obex. Discrete bipolar electrical stimulation was administered at sites in the dorsal medulla of spontaneously breathing rats in the vicinity of the caudal nucleus tractus solitarius (NTS) and adjacent reticular formation. Cardiorespiratory responses were recorded during microstimulation at three separate stimulating frequencies to examine the functional interaction of cardiovascular and respiratory-related neuronal elements in the NTS. Microstimulation was conducted at sites in the dorsal and medial regions of the NTS beginning at the level of the area postrema and extending posteriorly through the rostrocaudal course of the NTS; microstimulation was also conducted at midline sites in the commissural region of the NTS and the ventral and ventrolateral regions of the caudal NTS. Microstimulation of loci in the reticular formation adjacent to these NTS sites did not elicit any cardiorespiratory responses whereas stimulation of individual NTS regions elicited specific patterns of cardiorespiratory responses. Specifically, microstimulation of the dorsal and medial NTS at the level of the area postrema elicited pressor responses associated with apneic/hypopneic responses whereas stimulation of midline sites in the commissural region, dorsomedial sites caudal to the area postrema and the ventral and ventrolateral areas of the caudal regions of the NTS elicited depressor responses associated with bradycardic and apneic/hypopneic responses. The most profound respiratory effects (i.e., apnea) and heart rate responses (i.e., bradycardia) were seen following stimulation of the ventral and ventrolateral regions of the caudal NTS. These findings support the notion that the caudal NTS is a major site for coordinating cardiorespiratory afferent information in the rat and it is also apparent from this study that specific regions of the caudal NTS demonstrate a functional coexistence of cardiovascular and respiratory-related neurons. Finally, the results from this study showing the regional specificity and frequency-dependent characteristics of cardiorespiratory response patterns elicited by microstimulation suggest that the local microcircuitry and intrinsic neuronal networks in the more caudal regions of the rat NTS are more complex and heterogeneous than hitherto revealed. PMID- 2590844 TI - Brain spectrin(240/235A): a novel astrocyte specific spectrin isoform. AB - We have previously demonstrated the existence of two distinct isoforms of spectrin in mammalian brain (23). Brain spectrin(240/235) is found primarily in neuronal axons and presynaptic terminals, and brain spectrin(240/235E) is located in neuronal cell bodies, dendrites and postsynaptic terminals, and oligodendrocytes. These isoforms are thought to play important roles in controlling the early events of synaptic transmission, axonal transport of organelles and vesicles, and lateral mobility of integral membrane proteins. In this study, we have utilized a panel of monoclonal antibodies to identify a novel astrocyte specific isoform(240/235A) with subunits of 240 kDa and 235 kDa in a 1:1 ratio. Double label indirect immunofluorescence has indicated that brain spectrin (240/235A) is distinct from brain spectrin (240/235E). This novel isoform located in the soma and processes of astrocytes may play a role in actin membrane attachment, cellular architecture, strengthening of the membrane fabric, and translocation of cytoplasmic organelles and vesicles. PMID- 2590845 TI - Post-mortem dopamine dynamics assessed by voltammetry and microdialysis. AB - The effects of total brain ischemia (decapitation) on striatal extracellular levels of dopamine (DA) dihydroxyphenyl acetic acid (DOPAC) and ascorbic acid (AA) in chloral hydrate anesthetized rats were monitored at 1-min intervals by differential normal pulse voltammetry (DNPV) with numerical deconvolution of the catechol peak. Changes in pH were assessed by the shift of AA oxidation potential and incorporated into the computational procedure. The AA peak showed a sharp, short-lived (less than 15 min) postdecapitation rise, followed by a slower secondary increase. The DA signal increased 100-fold in the first 20 min followed by a slow decline. DOPAC levels fell 80% within 15 min after death. The post mortem changes in extracellular DA and DOPAC were verified by a similar experiment using microdialysis. These observations probably reflect massive release and impaired uptake of DA combined with reduced monoamine oxidase activity. Changes in membrane permeability to DOPAC as a consequence of a post mortem drop in pH may also contribute to the decline in extracellular DOPAC levels. PMID- 2590846 TI - Ethanol-diazepam interactions on delayed match-to-sample performance in baboons. AB - Four juvenile male baboons were trained on a delayed match-to-sample (MTS) discrimination task. Single administration of 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 mg/kg diazepam (DZ) resulted in a dose-related increase in mean response time (MRT), with a maximum effect at 2.0 mg/kg. Administration of 0.25 mg/kg of DZ had no effect. Response time was increased significantly by 1.0 g/kg of ethanol (EtOH) but was not affected by 0.5 g/kg EtOH. There were no significant effects on the number of correct responses. Combined treatment of 0.5 g/kg of EtOH with 1.0 mg/kg DZ produced the same increase in MRT as the DZ alone. When 1.0 g/kg EtOH was administered with 0.25 mg/kg DZ. MRT decreased which was a significant improvement in performance as compared to the increase in MRT observed with either the EtOH or the DZ alone. Combined doses of 1.0 g/kg EtOH and 0.5 mg/kg DZ produced essentially the same increases in MRT as either dose alone. Similar results were obtained when 1.0 g/kg EtOH and 1.0 mg/kg DZ were combined and the increase in MRT was about the same for DZ alone and more than twice as great for the EtOH alone. Combined administration of the drugs had no significant effects on the number of correct choices. Since the administration of a combination of a low dose of DZ with EtOH appeared to prevent the increases in MRT observed with either drug alone and there were no observable effects on the number of correct response, these effects do not appear to involve cognitive processes but might be related to excitability changes in motor systems. PMID- 2590847 TI - [Gammagraphic imaging of pheochromocytoma using 131I-metaiodobenzylguanidine]. AB - The authors present their first experiences with scintigraphic examination of pheochromocytoma by means of 131I-metaiodobenzylguanidine (MIBG). In two of the eight patients examined, the already established diagnosis of pheochromocytoma and paraganglioma was confirmed, in two the examination yielded confirmation of the presumed diagnosis, and in the remaining four patients presence of the tumor was excluded. In conformity with literary data, the authors found the given examination to be suitable for: 1. confirming the diagnosis of pheochromocytoma in cases with unequivocal CT findings, 2. excluding extraadrenal activity, 3. detecting relapses or the occurrence of an extraadrenal tumor, 4. detecting not suspect manifold endocrine neoplasias, 5. establishing the diagnosis of malignant pheochromocytoma, and 6. for examining patients presenting with a family history of pheochromocytoma. PMID- 2590848 TI - [Kinetics of thyroxine in ontogenesis studies using the metabolism of radiothyroxine]. AB - Radiothyroxine turnover rate was studied postnatally in 9, 18, and 35 day old rats in various intervals during 24 hours after intrajugular injection. Value of fractional turnover rate indicated higher thyroid activity in 18 day old rats than in those aged 9 or 35 days. These results support our previous conclusions on the maturation of thyroidal regulatory mechanisms in this period of development which were based on the rate of radioiodine uptake and changes in serum thyroxine concentrations. In another series of animals, the distribution of radiothyroxine in comparison with distribution of radioiodide was studied 4 hours after intrajugular injection on days 8, 12, 16, 20, 24, and 30 of postnatal development. In case of hormone distribution, all values in the brain, liver, kidney, intestine, and serum were much higher in young animals than in adult 60 day old rats. Particularly, in the brain up to 16th day, the concentration of T4 was six times higher than in adult animals. The highest percentage of the injected radiothyroxine dose was found in the liver, intestine and stomach, total values in these organs exhibited a progressive increase from 20% on day 8 to 50% on day 24. When compared with litter-mates injected with inorganic radioiodide, the radioactivity in animals treated with hormone was in most organs markedly higher. The opposite results were found only in the stomach, i.e. the uptake of iodide exceeded the uptake of hormone. These results suggests, that differences between age groups are not due by differences in vascularity and although indirectly they may be considered as reflecting changes in size of thyroxine binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590849 TI - [Adaptation to low intensity positive radial acceleration during early ontogenesis]. AB - In 5, 12, and 25 day old laboratory rats of our own breeding LD50 for positive radial acceleration of the intensity of 5 g, 7.5 g and 10 g was established. Resistance was found to decrease with age. All animals exhibited full adaptation on repeated exposure to acceleration of 5 g or 7.5 g, and even 10 g over a period corresponding to 20% duration of the lethal dose for the initial age applied 3 times a day in 3 hour intervals. The resistance of the animals to oxygen deficiency was significantly increased as demonstrated by the survival of all animals 3 hours after their exposure to 10 g acceleration in a dose lethal for the given age. Adaptation is presumed to occur at tissue level. PMID- 2590850 TI - [Ultrastructure of cellular elements of the ductal system (striated ducts) in the parotid gland in white rats]. AB - The wall of the striated ducts in the parotid gland consists of only one cell type. It is formed by high prismatic cells whose most numerous organelles are mitochondria with cristae. At the cell basis the mitochondria together with the deep infoldings of the cell membrane constitute the so-called basal labyrinth. Besides morphological manifestations of water and electrolyte transport, also signs of secretory activity were observed, processing in three basic stages: 1. accumulation of secretion, 2. exocytosis of secretion, 3. resting phase. The secretory activity was manifested both in the form of small secretory granules with differently dense content of homogenous nature and by numerous protruding blebs of the apical plasmalemma of striated duct cells. The mode of exocytosis has not been fully elucidated. Conceivably, there may be an evacuation of the content of secretory granules into the apical cytoplasm which does no longer contain formed granules. Actual secretion occurs presumably by means of the protruding blebs containing membraneous or vesicular material. PMID- 2590851 TI - [Risk factors for cardiovascular diseases in childhood]. AB - Risk factors for atherosclerosis in children were studied in families where the father had suffered from myocardial infarction before the age of 45 years and in the families of the closest relatives. The values of metabolism of lipids and atherogenic indexes were compared with the findings in a series of children with no positive family history. In children of at risk families cholesterol and triglyceride values were increased in 34.3%, HDLc was decreased in 42.1%, and apoprotein B was increased in 53.1%. Of the atherogenic indexes the LDL/HDL ratio proved to be the most significant. More than half of the children from at risk families can be considered to be threatened with atherogenesis. These children have to be followed up regularly and great care is to be given to a proper regimen. PMID- 2590852 TI - [Toxoplasma antibodies in children in Slovakia with potential toxoplasmosis]. AB - Over the years 1984-1987, 829 children from the Slovak Socialist Republic, aged from 0 to 15 years, with suspect toxoplasmosis were examined for the presence of toxoplasma antibodies by the serodiagnostic methods RVK, NIR, and ELISA. The percentage of toxoplasma antibodies yielded by the individual methods was as follows: RVK--39.5%; NIR--74.4%; ELISA-IgG--67.7%; ELISA-IgM--60.4%. Based on these results the authors conclude that the child population up to the age of 15 years is an at risk group with an increased possibility of contracting toxoplasmosis by frequent contact with the soil, sand, water, and animals, as well as by consuming not adequately cleaned fruit and vegetables. To protect the child population from toxoplasmosis greater attention is to be given to hygienic, nutritional and serodiagnostic prevention. PMID- 2590853 TI - [Hemodynamic importance of the left atrium in patients with essential hypertension]. AB - Twenty-nine patients with essential hypertension and thirty-seven without cardiac disease were examined electrocardiographically, polycardiographically and echocardiographically. Both the proportion of the left atrial systole in the hemodynamics and the size of the left atrium were significantly greater in hypertonics compared to healthy subjects. The parameters of left ventricular systolic function did not differ significantly, the parameters of diastolic function were significantly lower in hypertonics. Evaluation of the size and function of the left atrium supplements the clinical assessment of the functional state of the left ventricle at a period of its normal global systolic function but diminished diastolic function. The insufficient informative value of the electrocardiographic criteria of changes in the size of the left atrium (so called Morris's index) and of the presence of the 4th heart sound in evaluating the severity of hypertension is pointed out. Since the presence of the 4th heart sound is clinically incorrectly interpreted, the need for consistency in its interpretation is emphasized. PMID- 2590854 TI - [Treatment and reconstruction of open fractures of the forearm with tissue loss]. AB - The importance of the forearm calls for attempts to preserve it and to restore its function even in severe injuries with extensive tissue loss. At early and comprehensive first surgical treatment providing sufficient perfusion good results can be achieved also in cases that do not appear promising at first sight. After treating the soft tissues fixation of the fracture is to be ensured externally and reconstitution surgery is to proceed according to the management plan. Of the reported series of 11 severe compound fractures the functional result of management was not favorable only in a single case. PMID- 2590855 TI - [Larval toxocariasis--a severe course of the manifest infection]. AB - The case of a 17 year old patient with severe course of toxocariasis is reported. Over a period of 6 months the patient developed signs of serious systemic condition with fever, respiratory infections, diarrhea, urticaria, weight loss, and muscular atrophies. The most remarkable organ derangements involved bilateral exudative neuroretinitis, severe degree of peripheral motoneuron derangement, and grave kidney damage with developing polyuria, hypokalemia, metabolic alkalosis and therapeutically hardly tractable hypertension. The most important laboratory findings were high erythrocyte sedimentation, absolute and relative eosinophilia, and hypergammaglobulinemia. Serological examination exhibited weak larval toxocariasis positivity. Treatment with Mintezol and subsequent administration of prednisone resulted in complete restoration of the clinical state, including organ and laboratory manifestations. The reported case documents the occurrence of larval toxocariasis in our population as well as the possibility of a very severe course of this parasitic infection in man. The therapeutic effect is remarkable since literary data have so far reported mostly unsatisfactory results of toxocariasis treatment. PMID- 2590856 TI - [Urogenital trichomoniasis and vaginal mycosis in female offenders--a repeat study 20 years later]. AB - The prevalence of urogenital trichomoniasis and vaginal mycosis in 698 female prison inmates in Bratislava was compared with the occurrence of the diseases recorded twenty years ago. The occurrence rate of urogenital trichomoniasis (40.97%) was only slightly reduced compared to the sixties (59.17%), yet it was still five times higher than in the current population. The occurrence rate of vaginal mycosis is much lower in delinquent women (2.3%) than in other women. Trichomonas vaginalis was most frequently present in the age group of 20-29 years (44.67%). All patients with urogenital trichomoniasis were cured with nitroimidazoles. The first treatment was successful in 98.25%, the second treatment with the same dose had a 100% efficacy. Repeated examination of 84 women after two months did not confirm the possibility of intramural infection. PMID- 2590857 TI - A rapid in vitro screening system for the identification and evaluation of anticancer drugs. AB - We report the development of an in vitro screening system that can be used to identify new anticancer drugs that are specifically cytotoxic for dividing cells. The screening system takes advantage of the potential of many cell lines, including tumor cells, to stop dividing when they are plated at high cell density. The cytotoxic effects of anticancer drugs on dividing (i.e., cells plated at low cell density) and nondividing cells (i.e., cells plated at high cell density) is measured by the incorporation of 51Cr. This in vitro system was evaluated by measuring the cytotoxic effects of the anticancer drugs cisplatin, thiotepa, doxorubicin, methotrexate, and vinblastine on the cell lines B/C-N, ME 180, and MCF-7. In this in vitro system the concentrations of the anticancer drugs that produced significant cytotoxicity on only dividing cells are similar to the concentrations that are used clinically. The fact that this in vitro system is rapid, simple, applicable to many cell types, and able to predict effective concentrations of anticancer drugs should make it useful for the screening of new anticancer drugs and for the design of preclinical studies. PMID- 2590858 TI - Papillary carcinoma of the thyroid: additional evidence in support of a familial component. AB - Although a higher incidence of medullary carcinoma of the thyroid is well known to occur in families with syndromes of multiple endocrine neoplasia (MEN II and III), an epidemiologic familial component has only very rarely been ascribed to papillary carcinoma. In this report we describe a mother and daughter presenting with neck masses at an early age and subsequently found to have metastatic papillary thyroid carcinoma documented on pathology following thyroidectomy. The occurrence of the neoplasm at an advanced stage in closely related individuals early in life suggests that underlying genetic factors may predispose to this malignancy. Familial papillary carcinoma of the thyroid may have a hereditary basis independent of its association with the syndromes of multiple polyposis and of multiple hamartomas, and thus may represent a new entity with characteristics which distinguish it as a distinct subset of the more common disease. PMID- 2590859 TI - Tumor growth-promoting effect of immunosuppressive substance in mice. AB - The effect of immunosuppressive (IS) substance obtained from cancerous ascitic fluid on tumor growth and host immunity in plasmacytoma X5563-bearing C3H/He mice is described. IS substance given in three injections, before and after tumor inoculation caused: (a) enhanced tumor growth, (b) marked reduction in survival times, (c) inhibition on Con-A response of spleen cells. Depressed natural killer (NK) activity was observed in normal and tumor-bearing mice treated with IS substance. The data presented here suggest that IS substance suppresses both humoral and cellular immunoresponsiveness and tumor cells evade immune surveillance or immunologically mediated removal. PMID- 2590860 TI - Cochleovestibular toxicity related to dichloromethotrexate. AB - A 69-year-old man receiving monotherapy for lung cancer with dichloromethotrexate (DCM), and without exposure to other chemotherapeutic agents or known ototoxic drugs, developed profound cochleovestibular dysfunction. The initial presentation was vestibular. This resolved, but unilateral hearing loss ensued and continued to progress to a total of 80 db loss in the low frequency range and 40 db in the high range, despite discontinuation of the drug. Because DCM may be used in combination with the known ototoxin cisplatin, the potential of DCM as an ototoxin should also be considered in such patients. PMID- 2590861 TI - The social implications of mind-body cancer research. PMID- 2590862 TI - Illness-related worry among cancer patients: prevalence, severity, and content. AB - The present study assessed the prevalence, severity, and other parameters of illness-related worry among 83 cancer patients receiving active treatment for their illness. Participants completed questionnaires assessing a variety of worry dimensions. In addition, a family member of each patient completed a brief questionnaire regarding their perception of the patient's illness-related worry. Nurse ratings of patients' clinic-related behaviors were obtained. Fifty-one percent (n = 43) of patients reported worry to be at least "somewhat of a problem." Fifteen percent (n = 12) reported it to be a significant to severe problem. Significant correlations included patients self-rating of worry and: nurse rating of clinic behavior, total score on a Worry Content Scale, ability to stop worrying once started, and impact of worry on mood and functioning. Rating by the significant other of how much of a problem worry was for the patient and whether the patient was a worrier preillness was also significantly correlated. There were no significant differences between "worriers" and "nonworriers" on demographic or disease variables. A logistic regression model using the categories of "worries" or "nonworriers" as a dependent variable found that women and patients reporting poor social support were more likely to report a problem with worry. However, a large amount of the variance remained unexplained. PMID- 2590863 TI - Issues involved in providing quality and optimal care for the cancer patient in the era of cost containment. AB - With increasing emphasis on cost containment in the health care field there is legitimate concern that the quality of medical care provided by health professionals and hospitals will deteriorate. There is no area of medicine where this fear is more evident than in the care of the patient with malignant disease. Treatment is often palliative, making quality difficult to evaluate and the costs of therapy and supportive care are among the highest in the health care arena. In the future it can be anticipated that the conflict between cost and the provision of quality/optimal care for the patient with or suspected to have cancer will increase. PMID- 2590864 TI - Papillary carcinoma of the thyroid: hereditary or radiation-induced? PMID- 2590865 TI - Worries of patients with cancer: another view. PMID- 2590866 TI - Watsonville nurses lead earthquake response. PMID- 2590867 TI - Aiken calls for novel remedies to shortage. PMID- 2590868 TI - Bay Area nurses dispense critical care and comfort. PMID- 2590869 TI - Induction of pulmonary antibodies to Pasteurella haemolytica following intraduodenal stimulation of the gut-associated lymphatic tissue in cattle. AB - The induction of pulmonary antibodies to a bacterial antigen following intraduodenal (D) stimulation of the gut-associated lymphatic tissue (GALT) was investigated. Six calves were divided into two groups of three calves each. The GALT-primed calves received an ID dose of live Pasteurella haemolytica A1 followed by a subcutaneous (SC) dose of killed P. haemolytica. The sham-primed calves received an ID dose of phosphate-buffered saline solution (PBSS) followed by a SC dose of killed bacteria. Serum and pulmonary lavage fluids were collected weekly from each calf and assayed for titers of leukotoxin neutralizing antibodies (LNA), as well as IgG and IgA (lavage fluids only) to P. haemolytica. The GALT-primed calves responded to the ID stimulation by bacteria with increased serum IgG. The sham-primed calves had no change in antibody titers following ID stimulation. The GALT-primed calves had increased serum IgG, lavage IgG and IgA and increased LNA titers in both lavage fluids and serum following the SC dose of killed bacteria. The sham-primed calves demonstrated only an increase in serum IgG following the SC inoculation. A challenge study to evaluate if antibodies induced by GALT stimulation could reduce pulmonary lesions was performed using six calves divided into two groups. One group received an ID dose of P. haemolytica followed two weeks later by a SC dose of killed P. haemolytica. The sham vaccinated calves received an ID dose of PBSS followed in two weeks by a SC dose of killed bacterin. Calves were challenged by an intrapulmonary dose of live P. haemolytica A1 eleven days after the SC inoculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590870 TI - Protection of dogs against death from experimental rabies by postexposure administration of rabies vaccine and hyperimmune globulin (human). AB - Two experiments on simulated postexposure treatment were carried out in dogs using human rabies immunoglobulin (RIGH) and human diploid cell vaccine for human use. In one experiment, when animals were challenged by injecting street virus into the masseter muscle and treated with a combination of RIGH and vaccine, 50% of the animals were protected from rabies. In the other trial, in which animals were challenged by injecting the virus into the femoral muscle, treatment with RIGH and vaccine protected all the animals against rabies. To our knowledge this is the highest rate of postexposure survival in animals reported to date. In addition, five out of eight (62.5%) dogs that received RIGH alone after the virus challenge were protected, while none of the animals receiving vaccine alone were protected from rabies. These trials suggest that animals can be protected from rabies by postexposure treatment. The route of exposure and timing of the administration of vaccine and hyperimmune serum would seem to be important. PMID- 2590871 TI - Persistent infections of a field strain of rabies virus in murine neuroblastoma (NA-C1300) cell cultures. AB - Rabies virus from the brain of a striped skunk (Mephitis mephitis) from Ontario was inoculated into murine neuroblastoma (NA-C1300) cell cultures. These cultures were incubated and the cells were subcultured every three to four days. The presence of viral antigen in the cell cultures was monitored by direct immunofluorescent staining and in the culture fluids by titration in either baby hamster kidney (BHK/C13) or NA cells or in experimental mice. The virus-infected NA cultures evolved from an initial high viral concentration in supernatant fluid through a period of decreasing titers of infectious virus in the supernatant fluids to a final phase where no infectious virus has been found following cell culture and animal inoculation methods attempted although the persistently infected cells remained 95-100% viral nucleocapsid antigen-positive. Possible mechanisms involved in the perpetuation of this infection are discussed. This is the first report of a persistent infection of cell cultures by a field strain of rabies virus. PMID- 2590872 TI - Influence of dietary charcoal on ochratoxin A toxicity in Leghorn chicks. AB - The ability of activated charcoal to adsorb ochratoxin A (OA) in vitro and to reduce the toxic effects of OA in vivo when added to the diet of growing Leghorn chicks was studied. Activated charcoal (50 mg) was able to adsorb 90% of the OA (150 micrograms) contained in 10 mL of citrate-phosphate buffer (pH 7.0). When 2 g of a complete chick diet were mixed with OA in buffer, it adsorbed 66% of the OA, while addition of 50 mg of charcoal to this mixture further reduced the concentration of OA to 11.8% of the control, an additional 65% compared to the diet alone. In the first of two feeding studies, charcoal addition of up to 10,000 parts per million (ppm) to diets (6.7% tallow) containing 9.93 mumol (4 ppm) OA kg-1 diet had no effect on OA toxicity. Feed consumption and weight gain, however, were reduced 10 and 20%, respectively, in chicks fed diets which contained 10,000 ppm of charcoal compared to those fed no charcoal. In the second study, reducing dietary tallow to 2% did not alter the effects of OA or charcoal on weight gain and feed to gain ratio, but birds fed OA with 10,000 ppm charcoal had an 8.5% increase in feed consumption. An additional management problem was associated with the propensity of charcoal to blacken the feed, the birds and their environment. Addition of charcoal to OA contaminated diets appeared to be an ineffective method for reducing the toxic effects of OA in growing chicks. PMID- 2590873 TI - Porcine focal symmetrical poliomyelomalacia: test for an interaction between dietary selenium and niacin. AB - Experiments were conducted to test the hypothesis that dietary supplementation with nicotinamide would retard or eliminate the signs of selenium induced porcine focal symmetrical poliomyelomalacia (PFSP). Mixed-sex feeder pigs, approximately five weeks old, were divided into four groups and daily received, by oral capsule, the following treatments: no supplementation (control); 2.86 mg sodium selenite per kg body wt (selenium only); 44 mg nicotinamide per kg body wt (niacin only); or both the niacin and selenium (niacin + selenium). Over the ten day treatment body weights and behavior scores were recorded, as well as collection of fluid (blood, serum, urine) samples. Upon death, tissue samples (kidney, liver, brain, spinal cord and muscle) were obtained. All of these samples were analyzed for total selenium and bioactive niacin compounds. After gross pathological analysis, 11 samples from specific brain and spinal cord regions were taken for fixation and processing for histological analysis by light microscopy. The selenium only group showed behavior signs related to PFSP after two days of treatment with the average time of death at 6.5 days. Tissue levels of selenium were elevated and histological analyses established the expected lesions of PFSP. No disorders were noted in the control and niacin only groups. The niacin + selenium groups had slightly retarded changes in behavior scores (first differences from controls on day 4) but their mean day of death (7.5 days of treatment) did not differ from that of the selenium only groups. Histological analyses of these tissues revealed similar lesions to the selenium only group, but they may have been of lesser magnitude. The data were consistent with, but only partially supportive of, the above hypothesis. PMID- 2590874 TI - Follow-up studies by peroral gastric biopsies and necropsy in vomiting dogs. AB - The results of follow-up studies in 139 vomiting dogs are presented. Follow-up studies were performed by biopsies in 34 dogs, by biopsies and necropsy in six dogs and by necropsy only in 99 dogs. The times between the first and the last series of biopsies varied from three to 1042 days and from one to 656 days between the first series of biopsies and necropsy. From the 55 dogs with gastritis in the first series of biopsies, 35 also showed gastritis in the following biopsies or at necropsy. These were mainly severe types of gastritis such as diffuse, hypertrophic or atrophic. Ten dogs with superficial gastritis showed no gastric changes at necropsy, two dogs had edema only and three dogs had gastric changes other than gastritis, such as multiple polyps. In general, carcinoma and lymphosarcoma were found in the biopsies as well as at necropsy, but in three cases of terminal carcinoma only gastritis had been diagnosed initially. In 35 dogs the first series of gastric biopsies showed no pathological changes, but in 22 of these dogs gastritis, ulceration, fibrosis, atrophy, gastric dilation with local necrosis, and perforation or lymphosarcoma of the submucosa were found in the second series of biopsies or at necropsy. Several dogs which did not have gastric changes at necropsy had enteritis or intestinal lymphosarcoma. PMID- 2590875 TI - Follow-up studies by large intestinal biopsies and necropsy in dogs with clinical signs of large bowel disease. AB - The results of follow-up studies in 77 dogs with clinical signs of large bowel disease are presented. In 32 dogs colonic and/or rectal biopsy follow-up studies were done, combined with necropsy in seven dogs. In 45 dogs a follow-up necropsy only was done. The time between the first and the last series of biopsies varied from three to 729 days and between the first series of biopsies and necropsy from one to 980 days. Colitis found in 45 dogs in the initial biopsies was still present in 29 cases in the follow-up biopsy studies and/or at necropsy. Eleven cases showed hystiocytic ulcerative colitis. In general, adenoma, carcinoma and lymphosarcoma were confirmed in the follow-up examination, except for one adenoma, which appeared to be a carcinoma at necropsy. In cases in which the differential diagnosis was adenoma or carcinoma, the necropsy diagnosis was always carcinoma and in cases of a differential diagnosis of lymphosarcoma and/or colitis, lymphosarcoma was always diagnosed at necropsy. Several dogs without colonic changes in the initial biopsies had other gastric or small intestinal lesions at necropsy such as gastritis and enteritis of the small intestine, or tumors, in these areas. PMID- 2590877 TI - Caudal epidural analgesia in cattle using xylazine. AB - Each of 25 mature Holstein cows were given a single 5 mL epidural injection of one of four different concentrations of xylazine or saline. The onset, magnitude and duration of caudal epidural analgesia was quantitated with the use of a low voltage DC current applied to the perineal area. The dose that produced the longest duration of analgesia and produced the least ataxia or sedation was approximately 0.05 mg/kg (25 mg in 5 mL diluent). The analgesia produced by this xylazine dose was compared to a standard dose of epidural lidocaine (100 mg/5 mL) by the same method. To investigate the role of systemic absorption in the production of epidural analgesia, the previously utilized epidural xylazine dosage was given intramuscularly to four adult cows. Analgesia was quantitated as before and the results compared with epidural xylazine. Epidural xylazine produced a significantly greater duration of analgesia, as measured by this model, than did epidural lidocaine. Xylazine, given epidurally, produced greater perineal analgesia than did xylazine given intramuscularly. PMID- 2590878 TI - Isolation, characterization and in vitro mitogenic stimulation of peripheral blood lymphocytes from an American buffalo. AB - A rapid and reproducible method is described for the isolation and characterization of leukocytes from the peripheral blood of an American buffalo (bison). Centrifugation of the buffy coat cells on a Percoll gradient (1.079 g/mL) at 650 x g for 20 min resulted in the separation and high yields of pure viable leukocytes. The sheep erythrocyte-rosetting technique (ER) showed that 59% of the cells were ER+ (T lymphocytes). Fluorescein isothiocyanate (FITC) conjugated peanut agglutinin and FITC-conjugated concanavalin A revealed 77% and 89% positive cells, respectively. The isolated leukocytes contained adherent accessory cells and functionally active T and B lymphocytes which proliferated in response to both T and B cell mitogens and to exogenous recombinant bovine interleukin-2 in the absence and/or presence of the thiol compound 2 mercaptoethanol. PMID- 2590876 TI - The effects of feeding milk to diarrheic calves supplemented with oral electrolytes. AB - The effects of feeding different levels of milk to diarrheic calves (n = 19) supplemented with oral electrolytes were investigated. In the early stages of the disease the calves were fed either enough milk to maintain normal growth in a healthy calf, one half that volume or no milk. The three groups were further subdivided according to whether or not the electrolyte solution contained bicarbonate. A full milk ration allowed uninterrupted weight gains of 1% body weight/day (p = 0.003), but caused greater inappetence (p = 0.003 to 0.037) at the beginning of the trial than lower levels of milk intake. Electrolyte solutions with bicarbonate reduced growth rates in milk fed calves (p = 0.014). The density of fat stores increased with the level of milk feeding (p = 0.04 to 0.053). The mitotic index of the duodenal mucosa increased with milk feeding (p = 0.08), indicating a superior mucosal regeneration potential. Thymic atrophy was pronounced in those calves fed no milk (p = 0.001). It was concluded that the continued feeding of milk to diarrheic calves was beneficial. Electrolyte solutions containing bicarbonate should be avoided when milk is fed to diarrheic calves. PMID- 2590879 TI - Are cattle significant reservoirs of Coxiella? PMID- 2590880 TI - Payment for MRI professional services in British Columbia. PMID- 2590881 TI - Substance abuse and driving: the physician's role. PMID- 2590882 TI - So you want to have the baby at home? PMID- 2590883 TI - Physicians and the ecologic crisis. PMID- 2590884 TI - Standards of beauty: Degas v. Kirov. PMID- 2590886 TI - Third World aid. PMID- 2590885 TI - Physicians of the future. PMID- 2590887 TI - Fetal tissue transplantation: time for a Canadian policy. PMID- 2590888 TI - Fetal tissue transplantation: politics, not policy. PMID- 2590889 TI - Periodic health examination, 1989 update: 4. Intrapartum electronic fetal monitoring and prevention of neonatal herpes simplex. Canadian Task Force on the Periodic Health Examination. PMID- 2590890 TI - Diphtheria-tetanus overimmunization in children with no records: can it be prevented? AB - A pilot study was undertaken to assess the validity of two new tests for predicting the immune response of Toronto schoolchildren with no acceptable evidence of prior administration of diphtheria or tetanus toxoid to a routine booster injection of diphtheria and tetanus (DT) toxoid. The tests, an inexpensive enzyme-linked immunosorbent assay (ELISA) fingerprick test for tetanus antibodies and a modification of the Schick skin test for susceptibility to diphtheria, were administered before the booster injection. One week later the ELISA test was repeated and the result of the modified Schick test read. On both occasions a diphtheria microneutralization assay was done for "gold standard" evidence of prior exposure to diphtheria toxoid or toxin. The results were used to determine the sensitivity and specificity of a single prebooster tetanus ELISA test or a modified Schick test for predicting which children with no records could be safely protected with only one DT booster dose instead of the primary series of three or four doses usually given to such children. Only 6 of the 34 subjects (18%) were totally without prior exposure to tetanus toxoid. Two of the six (6% of 33 subjects) appeared to mount a primary immune response to diphtheria toxoid as well. An initial ELISA titre of 0.01 IU/ml or lower correctly identified all six children needing a full series of tetanus toxoid (sensitivity for a primary immune response 100%) and falsely identified only 3 of 28 immune children as needing the series (specificity for immunity 89.3%). The modified Schick test appeared to have even greater accuracy for identifying children needing a full series of diphtheria toxoid. However, its use, entailing the costs of an extra nurse visit, would have prevented only seven more children from receiving an unnecessary full series of diphtheria toxoid than use of the baseline tetanus ELISA test alone. PMID- 2590891 TI - Amiodarone-related cyclic thyroid dysfunction. PMID- 2590892 TI - Hypolipemic drug therapy. PMID- 2590893 TI - In vino veritas? Alcoholics and liver transplantation. PMID- 2590894 TI - Computerized chart organization and problem solving in a family practice. PMID- 2590895 TI - Why are Canada's nurses quitting? PMID- 2590896 TI - The Alzheimer's household: who cares for the caregivers? PMID- 2590897 TI - Cancer prevention. PMID- 2590898 TI - Cancer nursing--a problem-finding survey. The London Nursing Research Consortium. AB - A survey was conducted to identify the most difficult patient-care problems encountered by nurses who care for patients with cancer and the most difficult problems personally experienced by nurses as a consequence of caring for these patients. Nurses who provided care to patients with cancer in two community health agencies, one cancer treatment center, one chronic care hospital, and three acute care hospitals were invited to participate. A total of 566 nurses responded (43% response rate). Results are presented by total sample for 15 top ranked patient care problems, 10 top-ranked physical care problems, and 5 top ranked personally experienced problems. Results are also presented as a qualitative analysis of 1,052 comments made by respondents. For all groups of nurses within the total sample, coping with diagnosis, disease progression, and emotional response comprised the top-ranked patient care problems. Nutrition and pain management were top-ranked physical care problems. Top-ranked personally experienced problems paralleled patient care problems. A comparison of study findings with two previous surveys to identify research problems indicated high consensus about important areas for cancer nursing research. Scott, Oberst, and Dropkin's Stress-Coping model will be used to guide development of the research program that began with this problem-finding survey. PMID- 2590899 TI - Accidental acute exposure to doxorubicin. AB - Accidental ocular exposure to doxorubicin was followed by no reaction or rapidly resolving conjunctivitis in 13 of 15 cases (87%). In the two remaining cases, persistent photophobia and chronic inflammation were reported. Of 28 accidental exposures to sites other than the eyes, no reactions or rapidly resolving local reactions were reported in 24 cases (86%). Nurses are at particular risk for accidental exposure to doxorubicin and accounted for 20 of the 43 reported exposures (47%). PMID- 2590900 TI - Continuity of care. Development and implementation of a shared patient data base. AB - Although the inpatient Oncology Unit, the Medical Oncology Clinic, and Radiation Oncology provided care for many of the same patients, there was no mechanism for sharing nursing information, and little colleague input from one area to another. In order to meet this need, a nurse from each of the clinic areas was added to the inpatient unit's Patient Care Evaluation Committee. Working through this committee, these nurses developed an Inpatient/Outpatient Data Flow Sheet, which could be initiated in any oncology area to implement information flow when a patient was to be seen in a different setting. It proved to be an effective tool. The flow sheet, along with our rationale, was then presented for consideration as a computerized program to be used between the three areas. After careful investigation, it was approved. This provided the oncology areas with the first data storage capability for nursing in the hospital. It offered oncology nurses in distinct and separate areas access to obtain and update information on shared patients. This manuscript will focus on the computer program and the data base designed for the oncology department and its impact on nurses and patients. PMID- 2590901 TI - Factors influencing black women's breast self-examination practice. AB - This descriptive correlational study of 95 black women was designed to investigate breast self-examination (BSE) practice and examine the relationship among the frequency of BSE and health locus of control, breast cancer knowledge and demographic factors. Results showed that the majority of women (67%) failed to follow the American Cancer Society recommendations and reported practicing BSE less frequently than every month. Over one-third of the women (35%) reported BSE practice less than every 6 months. Statistically significant associations were found between the frequency of breast self-examination and the variables age, prior experience with breast disease, and powerful other locus of control. The frequency of BSE practice was found to be age related with older women in the sample practicing BSE more frequently than the younger women (chi 24df = 12.81, p less than 0.01). Women without prior exposure to breast disease tended to practice BSE least frequently (chi 2 = 12.04, p less than 0.01). Belief that health professionals control a person's health, powerful other health locus of control, was strongest in women who practiced BSE least frequently (H = 9.43, p = 0.01). Breast cancer knowledge scores were found to be uniformly low with women answering only 57% of the questions accurately. Nurses can use this knowledge to develop interventions that promote BSE practice. Strategies are suggested for strengthening factors associated with practicing BSE. PMID- 2590902 TI - Factors women take into account when deciding upon type of surgery for breast cancer. AB - For women with stage I or II breast cancer, randomized trials have demonstrated no significant difference in survival rates between women receiving modified radical mastectomy (MRM) and women receiving breast conserving (BC) surgery. Therefore, many women are now in a position of having a choice between these two options. Twenty-two women who met the surgical criteria for having this choice were interviewed 1 to 2 weeks postsurgery to determine factors they had considered when deciding between MRM and BC, how much they wished to participate in decision-making, and the sources of information they used. The sample was purposefully limited to women attending one clinic in order to insure control over variables such as the information to which patients are exposed. When asked why they had chosen a given surgery, two factors, concerns about radiotherapy (p = 0.003) and body integrity (p = 0.04), emerged as significantly different for women choosing BC vs. MRM. Furthermore, women reported that participation in decision-making was important to them and that they had had sufficient participation in the decision-making process. Finally, they rated "people" sources of information as more important than written or visual materials, suggesting that nurses and other care providers are important in supporting women through the decision-making process. PMID- 2590903 TI - Platelet aggregation inhibitory effects of the new positive inotropic agents pimobendan and UD CG 212 in whole blood. AB - A method is described for studying platelet function in human whole blood immediately after venepuncture in order to evaluate the antithrombotic potential of new pharmacological agents. In this method, platelet aggregation is quantified by measuring the fall in single platelet count, by using a whole blood platelet counter. We have investigated the platelet aggregation inhibitory effects of the new positive inotropic agents pimobendan and UD CG 212 (reported to be Ca++ sensitisers and phosphodiesterase inhibitors), alone and in combination with dipyridamole. Venous blood was drawn directly into prewarmed (37 degrees C) plastic syringes containing anticoagulants (3.2% trisodium citrate solution) plus a platelet aggregation inhibitor. Spontaneous platelet aggregation (SPA) was studied by roller mixing aliquots of blood in the collecting syringes for 6 min at 37 degrees C. Collagen induced platelet aggregation was studied by incubating aliquots of blood with 1 microgram/ml collagen on a shaking water bath for 3 min. In the absence of an inhibitor, there was a 50% fall in single platelet count due to SPA and a 65% fall was induced by collagen. Both SPA and collagen induced aggregation responses were inhibited by pimobendan (0.5-10 microM) and UD CG 212 (0.5-10 microM), in a dose dependent manner. A combination of 10 microM dipyridamole with 2 microM pimobendan or UD CG 212 was markedly a more effective inhibitor of platelet aggregation than a high dose of either inhibitor alone. It is suggested that the present method is simple and rapid, with minimal sample processing, and therefore the results may be protected from serious artifacts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590904 TI - Premature ventricular contractions and reflex sympathetic activation in cats. AB - In 27 decerebrate cats under various experimental conditions, we studied the effects of programmed premature ventricular contractions on the impulse activity of preganglionic sympathetic fibres isolated from the third left thoracic ramus. Single extrastimuli increased the sympathetic discharge by 319(SEM 43)% [from 10.3(1.7) to 36(3.7) imp.s-1, p less than 0.05]. The neural response was significantly enhanced after bilateral vagotomy by 394(34)% [from 12(2.6) to 53.3(9.8) imp.s-1, p less than 0.05], but abolished when the stimuli were delivered during bilateral carotid artery occlusion. No sympathetic reflex response was observed in cats with chronic sino-aortic denervation. In eight cats, during occlusion of the left anterior descending coronary artery, the control sympathetic response was progressively and reversibly attenuated from 239(28)% to 36(14)%, at 90 s from the beginning of the occlusion. After bilateral vagotomy, this inhibitory interaction was no longer present and the sympathetic neural response to programmed stimulation was maintained throughout the occlusion period. The data indicate that the sympathetic reflex response initiated by baroreceptive deactivation could be attenuated by cardiac vagal afferent activity induced by coronary occlusion. PMID- 2590906 TI - Cryothermal mapping of the sinus node in dogs: a simple method of localising dominant and latent pacemakers. AB - To investigate the potential use of cryothermal mapping to localise the sites of the dominant and latent pacemakers of the sinus node, we compared the results of cryothermal and electrical mapping of the sinus node in 16 dogs. In all dogs, cooling (-5 to +5 degrees C) of a localised epicardial area of about 3 X 3 mm2 close to the sulcus terminalis (area 1) resulted in a decrease in heart rate and a change in the P wave configuration. Cooling of an additional area of up to 15 X 3 mm2 (area 2) while cooling of area 1 was maintained resulted in a further decrease in heart rate and a further change in P wave configuration until junctional rhythm occurred. In all dogs areas 1 and 2 could be identified within 5 min. The heart rate and P wave configuration returned to control following cooling suggesting no adverse effect of cooling on the sinus node in this temperature range. In dogs with sufficiently slow heart rates, recording from area 1 showed diastolic and upstroke slopes followed by primary negativity, indicating that area 1 was the area of the dominant pacemaker. Recording from area 2 showed only diastolic slopes indicating that area 2 was the area of the latent pacemaker. Compared to electrical mapping for identifying diastolic slope, upstroke slope and primary negativity or earliest atrial activation, cryothermal mapping is a simple, quick and safe procedure for localisation of the sinus pacemakers. Unlike recording of sinus nodal electrograms, cryothermal mapping can be performed in the presence of rapid heart rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590905 TI - Mechanically induced action potential changes and arrhythmia in isolated and in situ canine hearts. AB - Stretch of excised myocardial tissue causes electrophysiological and potentially arrhythmogenic changes in transmembrane action potentials but corresponding data of the intact mammalian heart are lacking. The effects of increases in ventricular volume and pressure on epicardial monophasic action potentials were therefore investigated in isolated, cross circulated and in situ canine hearts. In seven isolated hearts, increases in ventricular volume and pressure resulted in (1) a linearly related decrease in action potential amplitude (r = 0.988; slope = 0.41% amplitude.ml-1; volume intercept = 17.6 ml), mainly due to a decrease in maximum diastolic potential; (2) a decrease in action potential plateau duration (at 20% repolarisation) by 19 (SD 8)%; and (3) appearance of early afterdepolarizations, reaching up to 18% of total action potential amplitude. Afterdepolarizations occurred only when ventricular outflow was obstructed at end diastole but not at end systole. In eight in situ hearts, increase in left intraventricular pressure produced by transient occlusions of the ascending aorta was also accompanied by decrease in maximum diastolic potential and action potential plateau duration, and by appearance of early afterdepolarizations. In both isolated and in situ intact ventricles, the loading induced electrophysiological changes were associated with occurrence of ectopic ventricular beats. These data show that mechanical overload produces significant electrophysiological changes in the intact canine ventricle which may lead to arrhythmia. PMID- 2590907 TI - Mechanism of the apparent parasympathetic inhibition of adenosine induced heart rate slowing in the dog. AB - The inhibitory action of intravenously administered adenosine on the sinoatrial (SA) node is not expressed in the conscious dog in the presence of normal vagal tone. After pharmacological or surgical parasympathetic blockade, however, adenosine exerts a powerful negative chronotropic effect. In order to determine the reason why this action of adenosine is blocked by the intact parasympathetic nervous system, we measured the chronotropic effects of adenosine while applying a constant cholinergic stimulus to the SA node. In conscious dogs during a systemic infusion of acetylcholine at a rate sufficient by itself to inhibit the SA node, intravenous adenosine injections caused further dose dependent reductions in heart rate. In anaesthetised, vagotomised dogs, intravenous adenosine caused similar negative chronotropic effects with or without concomitant electrical stimulation of the vagus nerve. As an example, 5 mumol.kg 1 adenosine reduced heart rate by 22 (SEM 4)% from a baseline heart rate of 172(10) beats.min-1; when heart rate was lowered to 66(1) beats.min-1 by electrical vagal stimulation, this dose of adenosine reduced heart rate by 36(8)%. Propranolol had no effect on these responses. We conclude that there is no direct cholinergic inhibition of the negative chronotropic action of adenosine on the canine SA node but rather that the inhibitory action of systemically administered adenosine on the SA node is simply masked by the withdrawal of vagal tone in response to the arterial hypotension resulting from this mode of adenosine administration. PMID- 2590908 TI - Disappearance and appearance of isoenzymes of creatine kinase, lactate dehydrogenase and aspartate aminotransferase in the myocardium undergoing infarction. AB - Recent investigations have shown that cardiac isoenzymes change with mechanical overload and possibly with myocardial ischaemia. This complicates the interpretation of serum enzyme changes in acute myocardial infarction. We have therefore investigated the rate of release of isoenzymes from necrosing myocardium and the effect of ischaemia per se. Discrete myocardial infarction was produced in 35 male Wistar rats by ligation of left coronary artery. Six (n = 7), 12 (n = 6), 24 (n = 9), 72 (n = 7) h and 3 weeks (n = 6) after surgery, total and isoenzyme activities of creatine kinase (CK), lactate dehydrogenase (LD) and aspartate aminotransferase (AST) were measured in the infarcted myocardium. Untreated rats (n = 12) were used as the control (time 0). Sham operation was performed in 36 rats. During the early period (0 to 12 or 24 h) of infarction, each (iso)enzyme disappeared monoexponentially from the myocardium (mean r = 0.88) with different disappearance rates. Cytosolic isoenzyme fractions decreased more rapidly than mitochondrial fractions. CK MB and the LD-H subunit decreased faster than CK MM and the LD-M subunit. Such differences in the disappearance rate may be related to subcellular localisation of each isoenzyme. In the late period (72 h and 3 weeks), CK BB and the LD-M subunit showed significant reaccumulation in the infarcted myocardium. Although inflammatory cells can be responsible for the reaccumulation of LD-M subunit, the origin of CK BB is unknown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590909 TI - Studies on oxygen and extracellular fluid restrictions in cultured heart cells: high energy phosphate metabolism. AB - Although cultured heart cells are increasingly used for the study of cardiac metabolism, relatively little is known about their energy turnover. We studied the effects of anoxia with simultaneous restrictions of the volume of the extracellular medium ("ischaemia") on high energy phosphate catabolism in cells from neonatal rat ventricles, cultured for 5 days. The cells were incubated for up to 4 h in Ham-F10 medium either in the presence or in the absence of glucose. High energy phosphates in cell extracts and AMP catabolites in the incubation medium were measured by high pressure liquid chromatography. ATP and creatine phosphate content in normoxic cells did not change significantly, either in the presence or absence of glucose, and the values were similar to those found in the heart in vivo. Energy rich phosphates decreased during anoxia, and were more rapidly depleted during simultaneous oxygen deprivation and volume restriction. Glucose delayed the decline in high energy phosphates. In the presence of glucose, hypoxanthine uptake was higher during normoxia than in anoxia, whereas in "ischaemic" conditions some hypoxanthine was produced. In the absence of glucose, only minor changes were observed in hypoxanthine levels during anoxia, but hypoxanthine production was marked when anoxia was coupled with extracellular volume restriction. Adenosine levels were below the limit of detection. Inosine release was relatively low under all conditions, Xanthine release did not show variation, and anoxia suppressed urate production. Oxygen and glucose deprivation thus led to various degrees of ATP and creatine phosphate breakdown in cultured neonatal heart cells both during anoxia and in simulated "ischaemia". PMID- 2590910 TI - A non-invasive method for testing neural circulatory control in man. AB - Exaggerated cardiovascular responsiveness is common in young men and may cause non-specific symptoms and poor performance. Conventional autonomic function tests are not clinically useful. We have therefore designed a thermal entrainment method to evaluate sympathetic and parasympathetic cardiovascular function in subjects with dystonic symptoms and orthostatic intolerance. Oscillations of thermal gradient in the skin were produced by standardised periodic stimulation of the lower part of the arm with warm and cool water. Vasomotor activity of the skin induced oscillations of arterial blood pressure which were thought to be regulated by sympathetic and parasympathetic heart rate control and by oscillation of the sympathetically controlled peripheral vascular resistance. We tested the method in subjects with cardiovascular symptoms (n = 7) and controls (n = 7). At supine rest, the frequency response of the heart rate variability to the thermal stimulation at frequencies of 0.01, 0.02, 0.03 and 0.1 Hz was significantly different (p = 0.008) between symptomatic subjects and controls. The gain of the heart rate control was increased to 0.03 Hz [-1.3(SEM 0.5) dB v 3.8(0.8) dB, p = 0.068] and decreased at 0.1 Hz [-3.9(1.1) dB v -1.5(0.6) dB, p = 0.076] in the test group compared to the control group. At stimulus frequencies of less than 0.03 Hz the individual overall heart rate variability of the subjects with symptoms stayed below the mean control value, at 60(6) ms v 79(15) ms, p = 0.16. The cutaneous temperature oscillations at the site of stimulation, frequency response of the oscillations of the skin blood flow and respiration to the thermal stimulation, and mean heart rate were similar in the both groups. The results show that this thermal entrainment method quantifies the increased sympathetic and decreased parasympathetic cardiac control of subjects with dystonic symptoms. PMID- 2590911 TI - Whole blood aggregation, thromboxane release and the lyso derivative of platelet activating factor in myocardial infarction and unstable angina. AB - To investigate the pathophysiology of intracoronary thrombus formation we measured whole blood aggregation in response to ADP, platelet activating factor (PAF) and collagen, along with thromboxane B2 (TXB2) production during collagen induced aggregation, plasma TXB2 and plasma levels of lyso-PAF, in 38 subjects with and without ischaemic heart disease (12 with acute myocardial infarction, 9 with prolonged ischaemic chest pain without infarction and 17 normals). Lyso-PAF was measured, after in vitro acetylation to active PAF, by bioassay using 14C serotonin labelled rabbit platelets. TXB2 was measured by radioimmunoassay. Plasma TXB2 was elevated at presentation only in patients with myocardial infarction (p less than 0.01). While impedance aggregation was similar in the three groups, aggregation to collagen resulted in greater release of TXB2 in subjects with myocardial infarction (p less than 0.01), an abnormality persisting 2-4 months later. Plasma lyso-PAF levels were significantly depressed throughout the first week in subjects with infarction (p less than 0.002), but after 2 to 4 months the level was greater than in normal subjects (p less than 0.001), changes presently unexplained. It is possible that the disorder of platelet function preceded and predisposed to coronary thrombosis. The findings strengthen the grounds for aspirin therapy in acute myocardial infarction. PMID- 2590912 TI - Effect of MCI-176, a new calcium channel blocker, on large and small coronary arteries in dogs. AB - MCI-176, a new calcium channel blocker, increases coronary blood flow and may improve perfusion in ischaemic areas. Its vasodilating effects on large conductive coronary arteries and the resistive arterioles were therefore compared with those of diltiazem, nifedipine, glyceryl trinitrate and adenosine in anaesthetised open chest beagle dogs. Intracoronary injection of these compounds caused dose dependent increases in coronary flow associated with decreases in the resistance of resistive arterioles, and the rank order of potency was nifedipine greater than adenosine greater than MCI-176 greater than diltiazem greater than glyceryl trinitrate. The resistance of the large conductive vessels was likewise reduced by these agents, except for adenosine. Glyceryl trinitrate showed the highest selectivity to the large conductive vessels, while adenosine showed the lowest and calcium channel blockers were intermediate. Among three calcium channel blockers, MCI-176 had the highest selectivity to the large conductive vessels, while the duration of action was the longest with diltiazem; the duration of action of MCI-176 was intermediate. Thus, MCI-176 is a coronary vasodilator, the potency of which is intermediate between nifedipine and diltiazem, but it has the highest selectivity to the large conductive vessels among these three compounds. PMID- 2590913 TI - Expression and desensitisation of A2 purinoceptors on cultured bovine aortic endothelial cells. AB - Purine nucleotides and their metabolites are important mediators of vascular tone. Adenosine promotes relaxation of vascular smooth muscle, acting on the A2 subclass of purinoceptors. There is some evidence that these receptors are also present on vascular endothelial cells. We have therefore examined cultured aortic endothelial cells for adenosine (A2) sensitivity. Bovine aortic endothelial cells (AG4762) were obtained from the Institute of Aging cell repository (USA), and cultured in monolayer flasks. Adenylate cyclase activity in homogenates of AG4762 cells was increased by 5'-(N-ethylcarboxamido)-adenosine (NECA) greater than 2 chloroadenosine greater than adenosine. NECA dependent activation of adenylate cyclase was inhibited by 3-isobutyl-l-methylxanthine greater than theophylline greater than caffeine. The rank order of potency of these compounds identified the responses as mediated by A2 purinoceptors. Prolonged exposure of AG4762 cells to NECA in culture resulted in loss of A2 purinoceptor responsiveness, and purinoceptor activity could be restored to non-dividing densensitized cells by further culture in the absence of the desensitising agent. The cyclic AMP dependent phosphorylation of specific sites in endothelial cells may trigger a number of important biological events which are yet to be determined. PMID- 2590914 TI - Anti-arrhythmic effects of amiodarone and desethylamiodarone on malignant ventricular arrhythmias arising as a consequence of ischaemia and reperfusion in the anaesthetised rat. AB - The effects of amiodarone and its metabolite desethylamiodarone on arrhythmias induced by ischaemia and reperfusion were studied in vivo in the anaesthetised rat with transient regional ischaemia (7 min of left coronary artery occlusion) and reperfusion (10 min). Amiodarone or desethylamiodarone were administered intravenously either 10 min prior to ischaemia or 2 min prior to reperfusion. Control rats received an equivalent volume of vehicle. Administration of 5.0 mg.kg-1 amiodarone or desethylamiodarone prior to ischaemia reduced the incidence of ventricular tachycardia during the ischaemic period from 67% to 20% (p less than 0.02) and 47% respectively. During reperfusion, mortality was reduced from 53% to 7% and 7% (p less than 0.02) respectively, and reperfusion induced ventricular fibrillation from 73% to 20% (p less than 0.01) and 47% respectively. When the drugs were given prior to ischaemia, the plasma concentrations of amiodarone and desethylamiodarone were 1.03 (SEM 0.18) and 0.22(0.02) micrograms.ml-1 and the myocardial concentrations were 23.43(2.78) and 30.41(1.87) micrograms.g-1 respectively. Similar concentrations were found in plasma and myocardium with drugs given prior to reperfusion. No significant differences in plasma or myocardial concentrations of amiodarone or desethylamiodarone were observed between animals which developed ventricular fibrillation and those which did not. In conclusion, this study demonstrates that desethylamiodarone can, like its parent compound, protect the heart against malignant ventricular arrhythmias arising as a consequence of regional myocardial ischaemia and reperfusion. PMID- 2590915 TI - Beneficial effects of oxypurinol pretreatment in stunned, reperfused canine myocardium. AB - The mechanism of reperfusion induced injury in acutely ischaemic myocardium is controversial but may be connected with oxygen free radical generation. However, chronic allopurinol treatment has beneficial effects in ischaemic myocardium which are not due to its inhibition of xanthine oxidase induced oxygen free radical production. Allopurinol is rapidly metabolised to oxypurinol, so we have examined the effects of this compound on nutrient blood flow and contractility in a canine model of stunned, reperfused myocardium. Twenty anaesthetised dogs underwent 15 min of total circumflex artery occlusion followed by 15 min restricted reflow and 2 h full reflow. Posterior wall thickening was determined by sonomicrometry and expressed as % control function. Regional myocardial blood flow was measured by microsphere technique and expressed in ml.min-1.g-1. Dogs in the treatment group (n = 10) received 25 mg.kg-1 oxypurinol as a 5 min left atrial infusion, 15 min prior to circumflex occlusion. Controls (n = 10) received a saline infusion. During occlusion mean circumflex pressure (17.6 v 18.2 mm Hg), endocardial flow [0.02(SEM 0.01) v 0.03(0.01) ml.min-1g-1], and area at risk [31.4(1.2%) v 34.6(2.4%)] were similar for both groups (control v treated respectively). Endocardial blood flow increased following acute administration of oxypurinol: 1.57(0.15) v 0.92(0.15) ml.min-1g-1 in control (vehicle) group, p less than 0.05. This effect persisted for the duration of the experiment, with a significant increase during early reflow: 1.83(0.32) v 0.74(.21), p = 0.03. There was also a marked increase in posterior wall function in the treated group, at 54.6(5.5)% v 5.1(8.4)% in the control group (p = 0.0003). These results show that pretreatment with oxypurinol protects acutely ischaemic myocardium, producing enhanced myocardial blood flow, diminished systolic bulge during occlusion, and markedly enhanced function recovery following reperfusion. PMID- 2590916 TI - Compilation of regression equations employing the RR interval for the correction of systolic time interval measurements for heart rate in sheep. AB - The aim of this study was to determine the validity of regression equations relating RR interval and heart rate to systolic time intervals in sheep. Regression equations were compiled employing the RR interval to correct systolic time intervals for heart rate in six Merino ewes. A range of heart rates was obtained by means of pharmacological intervention as well as electrical pacing. Heart rate did not affect the pre-ejection period, isovolumetric contraction time, the pre-ejection period to left ventricular ejection time ratio, the ratio QS2/QT, electrical delay (Q1), or the PR interval. Heart rate did, however, affect the duration of electromechanical systole (QS2), left ventricular ejection time and mechanical systole (S1S2). The study showed that it was preferable to correct the systolic time intervals using the RR interval rather than the heart rate. Bazett's equation to correct electrical systole (QT) for heart rate in humans was also validated in sheep. PMID- 2590917 TI - Specific frequency properties of renal and superior mesenteric arterial beds in rats. AB - In order to investigate the effects of arterial beds on pressure waveforms in arteries, the pressure waves observed in the rat tail artery were resolved into their Fourier moduli before and during ligation of the left renal artery and the superior mesenteric artery. Consistently different patterns of waveform changes in the tail artery were seen on occlusion of these vessels. Ligation of the renal artery reduced, and of the superior mesenteric artery increased, the pressure harmonics over most of the spectra. These results imply that to study the changes in the pressure contours as the observation point is moved downstream, one may have to account separately for the contributions of individual arterial beds. This is relevant in considering the degree to which it is appropriate for data to be amalgamated in models of the systemic arterial bed. PMID- 2590919 TI - Metabolic and haemodynamic changes in the heart during the early phase of cardiopulmonary bypass: II. Animal experiments. AB - A significant release of lactate instead of uptake was observed during the first 10 min of cardiopulmonary bypass preceding aorto-coronary bypass surgery in human patients. To clarify these findings in more detail, myocardial lactate and oxygen metabolism was studied in healthy dog hearts subjected to a protocol similar to the clinical situation. In one group (n = 11) normothermia at 34 degrees C was used with an empty beating heart, and in the other group (n = 11) hypothermia with ventricular fibrillation was applied. Within the first 10 min of bypass no significant changes in high energy phosphates were observed in myocardial biopsies. However, a marked decrease in mean aortic blood pressure and a simultaneous lowering in oxygen consumption was observed in both groups after instalment of bypass. An initial shift from lactate uptake to lactate release occurred while on bypass in the normothermia group. After 10 min of bypass, lactate uptake was restored in hearts of both groups. Therefore, the lactate release during the initial phase of bypass in patients originates both from the instalment of the bypass and from (local) inadequate perfusion, which is most likely to be due to stenosed coronary arteries. PMID- 2590918 TI - Metabolic and haemodynamic changes in the heart during the early phase of cardiopulmonary bypass: I. Clinical observations. AB - Knowledge of the effects of cardiopulmonary bypass on the myocardium and on cardiac function is limited. We therefore studied changes in haemodynamics and myocardial metabolism during the initial phase of cardiopulmonary bypass in two patient groups. In one group "normothermia" (34 degrees C) was used while on bypass, with an empty beating heart; in the other group hypothermia (range 27-33 degrees C) with ventricular fibrillation was used. Mean aortic pressure and myocardial oxygen consumption decreased significantly in both groups after instalment of CPB. The arterial-coronary sinus differences in lactate changed to negative values within 5 min of the start of bypass, indicating release instead of uptake of lactate. This release was maintained during the observation period and increased significantly in the hypothermic patient group when the ventricles were fibrillating. Therefore in patients undergoing aorto-coronary bypass surgery, detrimental changes in the myocardium must be anticipated during the initial phase of cardiopulmonary bypass prior to aortic cross clamping. PMID- 2590920 TI - Endocardial injury and the pathogenesis of mural thrombosis in the left ventricle. AB - To define the interactions between blood and endocardium damaged by lactic acid, the left ventricles of 48 isolated continuously perfused and beating hearts were exposed for 0-4 hours to Krebs Henseleit buffer (KHB) with or without 33 mumol.ml 1 of lactic acid (pH 6.4). After excising its apex, the left ventricle was flushed with KHB, followed by 10 ml of lightly heparinised blood, and then by a further 10 ml of KHB. Lactic acid caused endothelial cell membrane rupture, intercellular separation, and exfoliation with exposure of the basal lamina and underlying connective tissue. Whereas multilayered platelet aggregations formed on exposed basal lamina, fibrin deposition and incorporation of blood cells were only observed in the larger thrombi which formed on exposed collagen. These findings indicate that a metabolite which accumulates in ischaemic myocardium can cause endocardial injury which would predispose to the mural thrombosis which can complicate myocardial infarction. PMID- 2590921 TI - Apparent inosine uptake by the human heart. AB - Although inosine has been used clinically to support the myocardium, no data are available on the fate of exogenous inosine in the human heart. We therefore infused six patients, catheterised for coronary angiography, with inosine (5 mg.kg-1.min-1 intravenously) for 6 minutes. Before infusion, the arterio-venous difference of inosine, hypoxanthine and xanthine across the heart was nil. During infusion, arterial inosine increased substantially, exceeding the coronary sinus concentration by a maximum of 200 (SEM 53) mumol.litre-1, p = 0.02, at the fourth minute. Arterial hypoxanthine and xanthine also increased, while the arterio venous difference became 16(11) and 10(3) (p = 0.04) mumol.litre-1, respectively. Left ventricular dP/dtmax increased by 22(7)% (p = 0.04) at the end of infusion. Thus, there seemed to be substantial uptake of inosine by the human heart, followed by improvement in haemodynamics. PMID- 2590923 TI - Oxidative damage in selenium deficient hearts on perfusion with adriamycin: protective role of glutathione peroxidase system. AB - The protective effects of the glutathione peroxidase system against functional damage induced by perfusion of isolated hearts with adriamycin, an anthracycline antibiotic, were studied. We used selenium deficient rats, in which cardiac glutathione peroxidase activity was only 3% of control rats. Both contractile tension and coronary flow decreased during perfusion with the antibiotic. The degree of decline was significantly greater in the selenium deficient hearts than in the control hearts. The increase in malondialdehyde, a product of lipid peroxidation, induced by adriamycin perfusion was more evident in selenium deficient hearts, though the level of reduced glutathione was well maintained. Isolated mitochondrial function also decreased after aerobic adriamycin perfusion and the decrease was greater in selenium deficient rats. These observations indirectly suggest that the decrease in cardiac function induced by adriamycin is protected by the glutathione peroxidase system and that the decrease may be due, at least in part, to damage to the mitochondria caused by oxygen radicals generated by adriamycin. PMID- 2590922 TI - Vascular smooth muscle responsiveness to noradrenaline and phenylephrine following experimental heart failure in dogs. AB - Adrenergic vascular responsiveness was assessed in the dorsal pedal artery and the saphenous vein in dogs before and after the development of congestive heart failure (CHF). Following development of severe CHF, both noradrenaline and phenylephrine could produce a greater maximum tension and a shift of the resultant concentration-effect curve to the left compared to the curves seen before the development of CHF. The saphenous vein was more sensitive than the dorsal pedal artery to both agonists before CHF. After CHF, the sensitivity difference to noradrenaline increased significantly but it remained unaltered to phenylephrine. Relative to noradrenaline, phenylephrine became more potent on the artery at peak CHF, whereas the potency ratio was unchanged in the saphenous vein at peak CHF. Prazosin was a competitive antagonist only against phenylephrine prior to CHF; competitive antagonism was not seen against noradrenaline or following CHF. Prazosin was less effective in antagonising noradrenaline induced contractions, as shown by an increase in IC50 values. These results are consistent with increased tissue sensitivity to adrenergic agents during CHF. The greater potency of phenylephrine in the artery at peak CHF suggests the presence of a greater proportion of alpha 1 adrenoceptors, which is consistent with the decrease in effectiveness of prazosin after the development of CHF. PMID- 2590924 TI - Mechanism of arrhythmias induced by palmitylcarnitine in guinea pig papillary muscle. AB - Long chain acyl carnitines, intermediates of free fatty acid metabolism, have been implicated in malignant arrhythmias occurring during myocardial ischaemia. To investigate the mechanism of arrhythmia induced by these compounds the electrophysiological effects of palmitylcarnitine (30, 100 and 300 mumol.litre-1) on guinea pig papillary muscles was examined using the microelectrode technique. Palmitylcarnitine caused a time and concentration dependent shortening of action potential duration, with an increase in both developed and resting tension. After attaining the peak value of developed tension, delayed afterdepolarisations and/or aftercontractions were observed in three out of eight muscles on exposure to 100 mumol.litre-1 palmitylcarnitine and in all 13 muscles on exposure to 300 mumol.litre-1, while arrhythmia occurred in one out of eight muscles and in seven out of 13 muscles during these exposures. The amplitude and the coupling interval of delayed afterdepolarisations were dependent on basic cycle length. Delayed afterdepolarisations, aftercontractions and arrhythmias were completely abolished by ryanodine (1 mumol.litre-1). Though low Ca2+ (0.1 mmol.litre-1) abolished these activities, verapamil (4 and 10 mumol.litre-1) did not suppress them. Palmitylcarnitine (300 mumol.litre-1) shortened action potential duration to the same degree during metabolic block of either oxidative phosphorylation or glycolysis as it did in muscles exposed to oxygenated Krebs solution. Under these conditions, delayed afterdepolarisation and/or aftercontractions appeared in all muscles. We conclude that palmitylcarnitine could cause Ca2+ overload and trigger activity due to delayed afterdepolarisations and could act on the cell membrane independently of cardiac metabolism. We suggest that palmitylcarnitine is a factor in arrhythmogenesis during myocardial ischaemia. PMID- 2590925 TI - Effects of heart rate and diltiazem hydrochloride on alternans of ST segment elevation and ventricular arrhythmia during acute myocardial ischaemia in dogs. AB - Although the incidence of ventricular arrhythmias following myocardial ischaemia lessens as ischaemia improves, it is not clear whether this is correlated with a reduction in the degree of ST segment elevation. To explore this further we examined the effects of change in heart rate and the administration of the calcium antagonist diltiazem, 0.02 mg.kg-1.min-1, on ST segment elevation and the alternans of ST segment elevation (STA) and on serious ventricular arrhythmia induced by 10 min occlusion of the left anterior descending coronary artery in 86 mongrel dogs. The dogs were divided into three groups: 26 dogs paced at a rate of 180 beats.min-1 (group A); 44 dogs paced at a rate of 120 beats.min-1 (group B); and 16 dogs paced at a rate of 180 beats.min-1 and given diltiazem intravenously from 25 min before the coronary occlusion (group C). The degree of ST segment elevation and STA within 3 min of ischaemia was significantly lower in group B than in group A. There was no marked difference in the degree of ST segment elevation between groups A and C, but the STA was lower in group C than in group A. Incidence of ventricular tachycardia and ventricular fibrillation was significantly lower in groups B and C than in group A, and the timing of their first appearance was 4.5 (SEM 0.6), 4.2(0.9) and 3.0(0.4) min, respectively. We suggest that the reduction in serious ventricular arrhythmias associated with the decrease in heart rate was caused by the improvement of STA secondary to the improvement of ST segment elevation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2590926 TI - Myocardial surface PO2--an indicator of myocardial tissue oxygenation? AB - The validity of myocardial surface tissue PO2 (PtO2) as a reliable indicator of transmural myocardial tissue oxygenation was studied in six anaesthetised, open chest pigs. Epicardial surface PtO2 was correlated with other variables of myocardial tissue oxygenation such as regional blood flow, coronary venous PO2, O2 saturation, PCO2 and regional myocardial lactate extraction. The study design was based on an experimental model in which the effects of a pacing induced tachycardia on tissue oxygenation of ischaemic and normally supplied myocardium were measured. Two platinum multiwire surface electrodes were placed on the epicardium, on the areas supplied by the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (CX). The LAD was constricted to reduce mean surface PtO2 in the LAD area to about 50% of its baseline value. This did not affect surface PtO2 in the CX area. The reduction of surface PtO2 in the LAD area was associated with decreases in coronary venous PO2 and O2 saturation and with increases in coronary venous lactate and PCO2. Subendocardial regional blood flow and the subendocardial to subepicardial flow ratio were significantly lower than in the CX area. Increasing the heart rate by pacing (+45 beats.min-1) led to an increased degree of ischaemia as shown by fall in surface PtO2 in the LAD area to values around zero kPa, by marked increase in coronary venous lactate and PCO2, by reduction in total (-10%) and subendocardial (-40%) LAD flow and by deterioration of the subendocardial to subepicardial flow ratio. The increased degree of ischaemia was not accompanied by an increase in O2 extraction. The marked decrease in surface PtO2 occurred in spite of a slight increase in the subepicardial regional blood flow (+10%); thus the increase in O2 delivery was not sufficient to meet the increase in O2 demand. Total flow was increased by 27% in the CX area without changes in the subendocardial to subepicardial flow ratio and in the surface PtO2 values. When pacing was stopped, surface values of PtO2 in the LAD area returned to prepacing values, as did lactate extraction and coronary venous PCO2. Clear and close relationships with surface PtO2 were found for regional lactate extraction, coronary venous PCO2 and the normalised subendocardial RBF. Poor or no correlations were found for the normalised subepicardial regional blood flow, the coronary venous O2 saturation and the absolute values of subendocardial and subepicardial regional blood flow.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2590927 TI - Carotid chemoreceptor function and structure in the atherosclerotic rabbit: respiratory and cardiovascular responses to hyperoxia, hypoxia and hypercapnia. AB - We tested the following hypothesis: if carotid body blood flow, and hence the relationship of the frequency of discharge in chemoreceptor afferent fibres to arterial PO2, were affected by atherosclerotic change, then a modification of the control of the respiratory and cardiovascular systems might result. Carotid body reflexes were therefore studied in conscious atherosclerotic rabbits and a control group of normal animals breathing 100% O2, three hypoxic gas mixtures to which was added sufficient CO2 to maintain the arterial PCO2 constant, and 2% and 4% CO2 in 21% O2 and N2. When breathing room air, the atherosclerotic rabbits breathed at a higher respiratory frequency and lower tidal volume than the normal animals, although there was no difference in the respiratory minute volume. The respiratory and cardiovascular responses to hyperoxia, isocapnic hypoxia and hypercapnia were essentially the same in both groups of animals. Serial sections of the carotid bodies showed pathological changes including interstitial fibrosis in the caudal part with interstitial haemorrhages. The proximal part of the ascending pharyngeal artery, the vessel supplying the organ, and its origin from the external carotid, and the arterioles in the caudal part of the carotid body were nearly always occluded to a varying extent by atheromatous plaques. The capillaries appeared normal under light microscopy. The rostral-caudal lengths of the carotid bodies were similar in the two groups. We conclude that the peripheral arterial chemoreceptor responses in atherosclerotic rabbits are relatively normal even though the arteries to, and arterioles within, the carotid body are partly occluded. PMID- 2590928 TI - The differential response of normal and ischaemic Purkinje fibres to clofilium, d sotalol and bretylium. AB - To determine whether ischaemic tissue is more sensitive than normal tissue to class III anti-arrhythmic agents, we studied the effects of the class III agents clofilium, d-sotalol and bretylium on normal and ischaemic Purkinje fibres one day after ligation of canine left anterior descending coronary artery. In ischaemic Purkinje fibres superfused with normal Tyrode's solution (4mM K+, 2.7mM Ca+2) clofilium produced early afterdepolarisations at 10(-7)M and 10(-6)M, d sotalol at 10(-5)M to 10(-3)M, and bretylium at 10(-3)M. The early afterdepolarisation response of ischaemic tissue, which in some cases prolonged action potential duration to beyond 10 s, was significantly different from the simple prolongation of action potential duration seen in normal Purkinje fibres at the same concentrations. Clofilium and d-sotalol differentially produced early afterdepolarisations at or very near "anti-arrhythmic" doses. Therefore, class III anti-arrhythmics produced early afterdepolarisations differentially in ischaemic tissue at concentrations which did not produce early afterdepolarisations in normal tissue. PMID- 2590929 TI - The surface electrocardiogram as a means of refining a murine pressure overload model of congestive heart failure. PMID- 2590931 TI - Complex coronary angioplasty: use of a new microprobe balloon catheter. AB - Since the introduction of coronary angioplasty by Gruntzig et al. (Circulation [Suppl II] 56:84, 1977), a key determinant to overall success has been advancement in equipment technology. Major advances have been made in the availability of low-profile catheters in the last 5 years that have facilitated penetration of high-grade distal and complex lesions. The USCl probe TM catheter is an example of a low-profile catheter that has shown favorable applicability in dilating high-grade stenoses. Preliminary data indicate that this device has good trackability and an extremely low profile, which allows penetration of stenoses where other current low-profile catheters have failed. PMID- 2590930 TI - Study of the performance of 5 French and 7 French catheters in coronary angiography: a functional comparison. AB - The functional efficacy of a conventional 7F (high flow) coronary catheter (hand injection) was compared with a 5F (high flow) catheter using hand and powered injection in 29 patients with ischemic heart disease. Patients were randomized to 5F or 7F catheters as the initial catheter. Consecutive comparative coronary angiograms were performed in the 15 degrees right anterior oblique (RAO) view using Judkin's technique. Visual diagnostic grade (Grade 1 = Diagnostic, Grade 2 = Equivocal, Grade 3 = Nondiagnostic), vessel filling, vessel density (using a densitometer and corrected for background), streaming, and dislodgement were all evaluated independently by two experienced angiographers with correlation of results. Mean diagnostic grade (1.31 +/- 0.48) was significantly better with the 7F compared to 5F (hand) 1.72 +/- 0.81 and 5F (power) 2.00 +/- 0.71 (P less than or equal to 0.05) for each. Streaming was seen in 55% of injections with 5F (hand) versus 88.5% with 5F (power) and 20.7% with 7F. Measured vessel density was not different for the two catheters. Coronary injection dislodgement occurred significantly more often with 5F power injections than with hand injection of either catheter. Finally, in 6 (30%) of 20 patients in which the 5F was randomly the second catheter used, the operator had to revert to the 7F catheter in order to obtain adequate images. In conclusion, angiographic quality is reduced with 5F catheters compared to 7F high flow in certain patients. Thus, to achieve optimal diagnostic angiograms, larger lumen catheters may be required during certain procedures initially begun with 5F catheters. PMID- 2590932 TI - Catheter reperfusion for failed emergency coronary angioplasty without subsequent bypass surgery. AB - A transluminal intracoronary reperfusion catheter was used in eight patients, seven with acute myocardial infarction and one with unstable angina after failed emergency coronary angioplasty. After placement of the reperfusion catheter across the occlusion, symptoms of ischemia resolved in each patient. Chest pain recurred 3 hr later in a single patient who underwent successful repeat angioplasty. The catheter was withdrawn within 6 hr after introduction. Control coronary angiography showed a patent vessel in all but one. Repeat angioplasty or bypass surgery was unnecessary. During 1 year mean follow-up time all patients remained free of symptoms. The reperfusion catheter is a safe and effective means of perfusing a coronary artery after failure of thrombolytic therapy and coronary angioplasty in cases where emergency bypass surgery is not performed because operative morbidity is expected to outweigh the benefit of myocardial salvage, or when it cannot be immediately organized. PMID- 2590934 TI - Coronary spasm masquerading as progressive exertional angina with normal coronaries. AB - A case of typical exertional angina secondary to chronic focal vasospasm with normal coronary arteries and the role of vasospasm in typical angina are briefly discussed. Recommendations are made regarding evaluation of patients with normal coronaries and angina. PMID- 2590933 TI - Cough-cardiopulmonary resuscitation in the cardiac catheterization laboratory: hemodynamics during an episode of prolonged hypotensive ventricular tachycardia. AB - Cough-CPR, a deep rhythmic forceful cough repeated 30-60 times per minute, can be an effective resuscitative technique during emergencies occurring in the cardiac catheterization laboratory. We provide documented evidence on the potential of cough-CPR to maintain adequate systemic arterial blood pressure and consciousness during malignant ventricular arrhythmias, including the longest cough-CPR episode (75-90 sec), with continuous hemodynamics recorded. Results in three patients disclose that 1) mean arterial pressure during cough-CPR was 47-66% of nonarrhythmic baseline at a cough rate of 38-46% of normal sinus rhythm heart rate; 2) mean arterial pressure during hypotensive ventricular tachycardia was 17 60 mm Hg higher with than without cough-CPR; 3) at comparable diastolic pressures (33 vs. 31 mm Hg), systolic arterial pressure during cough-CPR was 40 mm Hg higher than basic CPR; and 4) consciousness can be maintained with cough-CPR during prolonged malignant ventricular arrhythmias. Thus cough-CPR can be a valuable adjunct in maintaining patient stability while definitive therapy for the malignant ventricular arrhythmia is administered. PMID- 2590935 TI - Optimal display of the coronary arterial tree with an upscan 1,023-line video display system. AB - Differences of opinion exist as to whether visualization of the coronary arterial tree is better with 525-line or 1,023-line video imaging systems. The 1,023-line acquisition has been associated with image degradation; 525-line display, however, has prominent raster lines that may also degrade the image. For evaluation of this issue, identical coronary arterial images were obtained with 525-line acquisition and then displayed with either 525-line or 1,023-line display. The 525-line acquisition with digital upscan 1,023-line display had superior image quality compared with 525-line display. With the use of 525-line acquisition and 1,023-line display, video images were similar to or slightly better than the identical cineangiographic images. PMID- 2590936 TI - Approach to the patient with left main coronary artery stenosis. PMID- 2590937 TI - Percutaneous transluminal coronary angioplasty using a combined "balloon-on-a wire" system and exchange guidewire technique. AB - New balloon-on-a-wire dilation systems allow crossing of severely stenosed coronary arteries owing to their ultra-low profile. However, these systems do not allow for over-the-wire exchange to a larger balloon catheter or insertion of perfusion catheters, should the vessel close abruptly during dilation. Therefore, if the need for such catheters arises, the vessel must be left unprotected during attempts to recross the lesion. We describe a new technique using a combined balloon-on-a-wire system and an exchangeable guidewire, which permits the crossing and dilation of severely stenosed coronary arteries, while at the same time offering vessel protection and balloon catheter exchange. PMID- 2590938 TI - Sterile "cable drape" reduces contamination. PMID- 2590939 TI - On percutaneous aspiration of a coronary thrombus. PMID- 2590940 TI - Stable binding of Drosophila heat shock factor to head-to-head and tail-to-tail repeats of a conserved 5 bp recognition unit. AB - The minimal DNA sequence required for the formation of a stable complex with Drosophila heat shock factor (HSF) in vitro is an inverted repeat of a 5 bp recognition unit, -GAA-. Surprisingly, both permutations of this 5 bp unit, head to-head and tail-to-tail, bind to HSF with similar affinity and with striking 2 fold symmetry. HSF also binds to longer arrays of inverted 5 bp units, and the size of the HSF footprint increases with the addition of each 5 bp unit to these arrays. However, the electrophoretic mobility of the HSF-DNA complexes decreases most distinctly with the addition of every three 5 bp units. Cross-linking of purified HSF in the absence of DNA generates complexes with the sizes expected of HSF trimers. We propose that trimers of HSF bind to DNA and that the number of HSF subunits in direct contact with DNA is determined by the number of correctly positioned 5 bp recognition units. PMID- 2590941 TI - A restricted cytoplasmic region of IL-2 receptor beta chain is essential for growth signal transduction but not for ligand binding and internalization. AB - The functional, high affinity form of interleukin-2 receptor (IL-2R) is composed of two receptor components, the IL-2R alpha (p55) and IL-2R beta (p70-75) chains. Unlike the IL-2R alpha chain, the IL-2R beta chain contains a large cytoplasmic domain that shows no obvious tyrosine kinase motif. In the present study, we report the establishment of a system in which the cDNA-directed human IL-2R beta allows growth signal transduction in a mouse pro-B cell line. This system enabled us to identify a unique region within the cytoplasmic domain of the human IL-2R beta chain essential for ligand-mediated signal transduction. We also demonstrate that certain cytoplasmic deletion mutants in the IL-2R beta chain, although deficient in signal transduction, can still form high affinity IL-2R in conjunction with endogenous mouse IL-2R alpha chain; the mutants are still able to internalize the ligand as well. PMID- 2590942 TI - Junctional sequences of T cell receptor gamma delta genes: implications for gamma delta T cell lineages and for a novel intermediate of V-(D)-J joining. AB - Nucleotide sequences of a large number of V-(D)-J junctions of T cell receptor (TCR) gamma and delta genes show that most fetal thymocytes express on their surface one of just two gamma delta TCRs known to be expressed by epidermal gamma delta T cells (s-IEL) or intraepithelial gamma delta T cells associated with female reproductive organs (r-IEL). In contrast, gamma delta TCRs expressed on adult thymocytes are highly diverse as a result of multiple combinations of gene segments as well as junctional deletions and insertions, indicating that developmental time-and cell lineage-dependent mechanisms exist that control the extent of gamma delta TCR diversity. In addition, this study revealed a new type of junctional insertion (P nucleotides), which led to a new model of V-(D)-J joining generally applicable to immunoglobulin and TCR genes. PMID- 2590943 TI - Monovalent cation-induced structure of telomeric DNA: the G-quartet model. AB - We have investigated the structures formed by oligonucleotides composed of two or four repeats of the telomeric sequences from Oxytricha and Tetrahymena. The Oxytricha four-repeat molecule (d(T4G4)4 = Oxy-4) forms structures with increased electrophoretic mobility in nondenaturing gels containing Na+, K+, or Cs+, but not in gels containing Li+ or no added salt. Formation of the folded structure results in protection of a set of dG's from methylation by dimethyl sulfate. Efficient UV-induced cross-links are observed in Oxy-4 and the related sequence from Tetrahymena (d(T2G4)4 = Tet-4), and join thymidine residues in different repeats. Models proposed to account for these data involve G-quartets, hydrogen bonded structures formed from four guanosine residues in a square-planar array. We propose that the G-quartet structure must be dealt with in vivo by the telomere replication machinery. PMID- 2590944 TI - Structure of the Drosophila BicaudalD protein and its role in localizing the posterior determinant nanos. AB - Mutations in the BicaudalD (BicD) gene lead to a global reorganization of the Drosophila body pattern such that the head, thoracic, and anterior abdominal segments are replaced by posterior abdominal segments and terminalia. We first provide evidence that the primary cause of this phenotype is the inhibition of two anterior factors, bicoid and hunchback, by mislocalized activity of the posterior determinant nanos. We then describe the isolation of the BicD gene and show that it encodes a coiled-coil protein similar to the carboxy-terminal portion of the myosin heavy chain. Finally, we find that BicD protein is uniformly distributed throughout wild-type oocytes but is concentrated at the anterior pole of BicD mutant oocytes together with ectopic nanos activity. Taken together, these results suggest that BicD encodes a cytoskeleton-like protein involved in transporting or anchoring the nanos morphogen within the oocyte cytoplasm. PMID- 2590945 TI - A Xenopus mRNA related to Drosophila twist is expressed in response to induction in the mesoderm and the neural crest. AB - We have cloned a Xenopus cDNA related to the twist gene, which is required for mesodermal differentiation in Drosophila. Northern blots of dissected embryos and in situ hybridization show that the corresponding mRNA, called Xtwi, first appears in early gastrulae, and is present only in mesodermal cells. Within the mesoderm, Xtwi is expressed in the notochord and lateral plate, but not in the myotome; therefore there is a complementary pattern of Xtwi and muscle-specific gene expression in the mesoderm. Xtwi expression therefore marks the subdivision of the mesoderm. Xtwi is also activated a few hours later in the early development of the neural crest. This gene is thus expressed in response to two sequential early inductions in frog development. PMID- 2590947 TI - Lassa fever: the first confirmed case imported into Canada. PMID- 2590946 TI - Primary sequence of a motor neuron-selective adhesive site in the synaptic basal lamina protein S-laminin. AB - S-laminin, a novel homolog of laminin, is concentrated in a subset of basal laminae including the basal lamina that passes between motor nerve terminals and muscle fibers at the neuromuscular junction. Here we used recombinant fragments to localize a neuronal attachment site to the C-terminal 10% of s-laminin. We then used synthetic peptides spanning the active fragment to identify the primary sequence of the adhesive site as Leu-Arg-Glu (LRE): neurons attach to an immobilized LRE-containing peptide, and soluble LRE blocks attachment of neurons to the s-laminin fragment. Whereas ciliary ganglion neurons (which normally innervate muscle fibers) adhered well both to laminin and to an s-laminin fragment, sensory and central neurons and several neuronal cell lines all adhered well to laminin but poorly to the s-laminin fragment. Together, these results define a motor neuron-selective attachment site on s-laminin. PMID- 2590948 TI - Interaction of N-alkylanthracyclines with lipid bilayers: correlations between partition coefficients, lipid phase distributions and thermotropic behavior. AB - The thermotropic behavior of multilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC), or of DPPC in admixture with cardiolipin or cholesterol, in the presence of various N-alkyl derivatives of both adriamycin and adriamycin-14-valerate has been investigated by high sensitivity differential scanning calorimetry. The analogues, particularly the 14-valerate derivatives, which were most lipophilic as judged by their lipid/buffer, and to a lesser extent by their octanol/buffer, partition coefficients, were the most effective in depressing the tm of the investigated lipids; correlations, however, were not absolute. Other factors, such as the distribution of the drugs between the solid and liquid-crystalline phases of the bilayer, were also important to the observed membrane perturbations. With all anthracyclines, however, no major changes in the transition enthalpy were observed. In the case of vesicles prepared from pure DPPC, curve fitting analysis based on ideal solution theory (J.M. Sturtevant (1984) Proc. Natl. Acad. Sci. USA 81, 1398-1400) applied at relatively low drug concentrations where single peak transitions were produced, adequately described the differential scanning calorimetric results. At high drug concentrations, however, the presence of multi-peak transitions were indicative of non-ideality. PMID- 2590949 TI - Effect of natural and structurally modified bile acids on cholesterol metabolizing enzymes in rat liver microsomes. AB - The effect of chenodeoxycholic (CDCA), ursodeoxycholic (UDCA), tauroursodeoxycholic (TUDCA), cholic (CA), ursocholic (UCA) acids, analogues of CDCA and UDCA with a cyclopropyl ring at C22, C23 (cypro-CDCA and cypro-UDCA) and 23-methylursodeoxycholic acid (MUDCA) on cholesterol 7 alpha-hydroxylase was studied in rat liver microsomes. Cypro-analogues consisted of a mixture of four diasteroisomers, while MUDCA was the racemic mixture of two enantiomers. Each steroid was added to liver microsomes at concentrations ranging from 10 to 200 microM. With the exception of UCA and CA, all the bile acids inhibited cholesterol 7 alpha-hydroxylase activity. The inhibition shown by cypro-CDCA and cypro-UDCA was stronger than that observed with the corresponding natural compounds. 22S,23S cypro-UDCA exhibited an inhibitory effect which was more pronounced than that of the diasteroisomer mixture. The isomer 22R,23S was less effective and decreased cholesterol 7 alpha-hydroxylase activity in a manner comparable to that of UDCA. The effect of CDCA, UDCA and the cyclopropyl analogues was also tested with respect to HMG-CoA reductase and acylCoA cholesterol acyltransferase (ACAT) activities. ACAT was stimulated by the isomer 22S,23S cypro-UDCA but not affected by the other bile acids. No effect was observed as regards HMG-CoA reductase. PMID- 2590950 TI - Fluorescence depolarization study on non-bilayer phases of phosphatidylethanolamine and phosphatidylcholine lipid mixtures. AB - The orientational order and rotational dynamics of 1-palmitoyl-2-[[2-[4-(6-phenyl trans-1,3,5- hexatrienyl)phenyl]ethyl] carbon yl]-3-sn-phosphatidylcholine (DPH PC) in dilinoleoylphosphatidylethanolamine (DLPE) and 1-palmitoyl-2 oleoylphosphatidylcholine (POPC) binary lipid mixtures were investigated. A previous study (Biochim. Biophys. Acta 731 (1983) 177) indicated that the empirical phase diagram of POPC/DLPE can roughly be divided into three zones. They are the lamellar (15% PC and higher), intermediate (5-15% PC) and inverted hexagonal (0-5% PC) phases. As the lipids changed from the lamellar to intermediate phase, the order parameter increased at all temperatures (1-50 degrees C). On the contrary, the rotational diffusion decreased at high temperatures (20-50 degrees C) but increased at low temperatures (1-10 degrees C). These results indicate that the intermediate phase is in a stressed state at high temperatures but in a highly mobile amorphous state at low temperatures. As the lipid progressed from the intermediate toward hexagonal phase, the order parameter decreased abruptly at all temperatures. The ratio of order parameter in the intermediate phase to that in the hexagonal phase was calculated. This ratio was found to increase linearly with temperature, indicating that a distinct change in the packing symmetry of lipids occurred as temperature increased. From the intermediate to hexagonal phase, the rotational diffusion increased slightly at high temperatures but declined abruptly at low temperatures. These results further agreed with the stressed and amorphous natures of the intermediate phases as described above. PMID- 2590951 TI - The effect of loperamide on the thermal behavior of dimyristoylphosphatidylcholine large unilamellar vesicles. AB - The effect of loperamide, a drug belonging to the opiate family, on dimyristoyl phosphatidylcholine large unilamellar vesicles (DMPC LUV) was investigated by quasielastic light scattering (QLS) and Fourier transform infrared spectroscopy (FT-IR). Both techniques show that, in the presence of loperamide, DMPC LUV undergoes a two step transition in cooling: one step around the transition point of pure lipid vesicles, the other at a lower temperature. The temperature of the latter step transition is different for the head and tail regions of the drug containing vesicles: FT-IR spectra demonstrate that the hydrophobic acyl chains transition starts at a temperature well above that of the interfacial region whereas the transition of the entire vesicle, explored by QLS, is broad and covers both temperature ranges. These transitions are thermally reversible in the FT-IR which measures local order but aggregation effects prevent the thermal reversibility of the QLS results. The nature of the drug-lipid interaction is also discussed. PMID- 2590952 TI - [Transitory vergences in multiple sclerosis]. PMID- 2590953 TI - [Vitreous hemorrhage and neovascular proliferation in multiple sclerosis]. AB - We report the case of a 40 year-old man with multiple sclerosis, who presented a bilateral proliferative retinopathy responsible for a vitreous hemorrhage. Examination of the periphery of the retina showed diffuse retinal periphlebitis; fluorescein angiograms showed a peripheral retinal ischemic syndrome with secondary neovascularization. Several recent studies have show that retinal periphlebitis is a frequent finding in multiple sclerosis; but to our knowledge a retinal ischemic syndrome with neovascularization has seldom been reported. PMID- 2590955 TI - [Medicolegal estimation of handicap: value of studying binocular visual fields]. AB - Estimation of disability for visual field defects by plotting the field binocularly, and establishment of percentage impairment with a binocular grid. PMID- 2590954 TI - [The value of an eye]. AB - The loss of unilateral visibility with other eye normal remain a moderate impairment. For the legal evaluation it is now necessary to separate the strict rate of physiologic reduction and the description of the other detriments and especially the professional functions. PMID- 2590956 TI - [The red blob of the artist Larrieu]. PMID- 2590957 TI - [Granuloma of the head of the optic nerve preceding systemic sarcoidosis]. PMID- 2590958 TI - [Value of nuclear magnetic resonance in hematoma of the optic nerve sheath. Apropos of a case]. PMID- 2590959 TI - [Orbital angioma with scleral erosion disclosed by detachment of the neuro epithelium]. AB - About a child presenting an orbital angioma associated with detachment of the retina, and malformative syndrome with facial fissure. Pathogenic discussion. Favourable evolution, after binding of pedicule. PMID- 2590960 TI - [Preliminary results concerning residual astigmatism of grafts following the use of Hanna's trepan]. PMID- 2590961 TI - [Treatment of recurrent pterygium using a lamellar graft. Apropos of 2 cases]. PMID- 2590962 TI - [Angle-closure glaucoma in patients with Galand's disk implant. Apropos of 3 cases]. PMID- 2590963 TI - [Sector proliferative retinopathy with localized vascular anomalies: apropos of 2 cases]. PMID- 2590964 TI - [Mydriasis posterior synechia in patients with pseudophakia]. PMID- 2590965 TI - [Acute panvasculitis]. PMID- 2590966 TI - [Macular disorders and carotid digital angiography]. PMID- 2590967 TI - [Glaucoma and Basedow's disease, physiopathogenesis and treatment]. PMID- 2590968 TI - [Comparative study of corneal radial centripetal and centrifugal incisions]. AB - The author presents a comparative study about the efficacity of centripetal incisions compared with centrifugal incisions. Centripetal incision is the best technic. PMID- 2590969 TI - [Epikeratophakia: reflections apropos of several personal cases]. AB - About some personal cases, the author explains the epikeratophakia technic, indications; complications, advantages and results. PMID- 2590971 TI - [Human grafts preserved at +37 degrees C. Initial clinical results]. AB - This study reports the clinical use of donor corneas stored at +37 degrees C in organ culture medium. Twenty-five penetrating keratoplasties were performed. The mean storage time of organ-cultured donor corneas was 12.3 days (3-21). The follow up of the patients was 12 months. The criteria for the survival of corneal grafts was mean central corneal thickness, clarity of the cornea and mean endothelial cell density. The graft survival was 92% at 12 months. The mean central corneal thicken was 0.54 mm. The mean endothelial cell density was 1625 cells/mm2. The mean decrease in endothelial cell density at 12 months was 40.6%. PMID- 2590970 TI - [Corneal abscess caused by Pasteurella following cat scratch injury]. AB - Authors report a Pasteurella Multocida corneal abscess after a scratch from a cat. The evolution was torpid and needed a transfixiant keratoplasty. They recall bacterial tanks, infestation ways, clinical manifestations and bacteriological identification. They note the low occurrence of ophthalmological manifestations and the sensibility of Pasteurella to various antibiotics, especially Beta lactams, phenicol and cyclins. PMID- 2590972 TI - [Inferior eyelid reconstruction. Various technics as a function of the length of substance loss]. AB - The authors expose the three technics for the inferior eyelid reconstruction which seem them now the most certain. If the defect is inferior at the quarter of the eyelid: suture with only one junction; if it is included between the quarter and the half of this length: tarso-conjunctival graft and cutaneous flap if it surpasses the half of the eyelid length: nasal chondromucous graft and temporojugal flap. PMID- 2590973 TI - [The visual field of patients with pituitary adenoma surgically treated]. AB - The authors report the evolution of 72 patient's visual field operated for one pituitary adenoma. They specify the constant amelioration of this investigation in chromophobic adenomas. The stability in prolactinic adenomas or somatotropic. Allowing the supervision of the visual case, at these patients, the visual field does not seem useful in the diagnosis of the tumors recurrence. PMID- 2590974 TI - [Diagnostic and therapeutic value of the panfundoscope in diseases of the posterior eye segment]. AB - The scope of this work is to evaluate the diagnostic and therapeutic value of using Schlegel's panfundoscope with respect to the three mirror lens on the basis of a double-blind comparative study. This method is especially rewarding for the follow-up of fundus lesions, their detection through opaque media and/or a poorly dilated pupil, as well as through an intraocular lens. Panretinal photocoagulation, prophylactic annular photocoagulation of peripheral retina and vitrectomy can be performed more easily through this lay-out. PMID- 2590975 TI - [Results and indications of aspiration drainage of subretinal fluid apropos of a series of 100 consecutive retinal detachments]. AB - Controlled vacuumed drainage of subretinal fluid is achieved using a 25 gauges butterfly needle and a syringe. This technique often totally flattens the retina during the operation. It seems particularly indicated in inferior retinal detachment without break. PMID- 2590976 TI - [Uncommon sites of metallic intraocular foreign bodies]. AB - The authors report one case of irido-corneal angle foreign body, three cases of intra-lens foreign body, and one case of foreign body located into the retino choroidal wall. For this last case, they describe an original technique of treatment including a retinal Argon-Laser photocoagulation round the foreign body followed by a foreign body extraction with endocular forceps and vitrectomy. PMID- 2590977 TI - [Penetrating eye injuries caused by firearms. Apropos of 17 cases]. AB - The authors present 17 cases of perforating ocular injuries caused by fire arms. They successively describe circumstances of trauma, initial injuries, surgical techniques employed and their results. The mean follow-up of patients is about one year. They particularly insist on severity of this type of trauma and legislative problems caused by free sale of some of these arms, more specially so called self defence pellets guns. PMID- 2590978 TI - [Intra-ocular implantation and traumatic cataract]. AB - Discussion of the indications of the correction of post-injury aphakia intraocular lens. The immediate infectious danger by perforation, the unavoidable inflammatory reactions, the potential retinal risk and the so often alteration of the posterior chamber by synechias, are leading to advice, in the majority of cases, the secondary anterior chamber lens implantations. PMID- 2590979 TI - [Prevention of retinal detachment by laser photocoagulation]. PMID- 2590980 TI - [Prevention of retinal detachment in Wagner-Stickler syndrome]. PMID- 2590981 TI - [Universal treatment of ophthalmic migraine]. AB - It's about a therapeutic method, particular to the author, which gets its universality from an optic prescription with a prismatic aspect. The ophthalmic headache's crisis is caused, in fact, by a spasm of convergence on an unknown exophory of which the amplitude of fusion is satisfying, and the presence of which can only be seen with test under screen. PMID- 2590982 TI - [A case of choroideremia]. AB - The authors describe a case of choroideremia. Discussion is upon clinical and evolutive data, others diagnosis, pigmentary retinopathy or rubeolic retinopathy at the beginning of the disease, diffuse chorio capillary atrophy, gyrate atrophy of the choroid and retina. Biomicroscopic finding of heterozygous females (the mother and his sister) are described. Genetic council is those of recessive X linked hereditary with the possibility of prenatal diagnosis using genic marker. PMID- 2590983 TI - [The frequency of acute glaucoma crises. Implications for the detection of the risk of angle-closure]. AB - Over a 5 year period 61 patients with acute angle closure glaucoma have been registered in Department Savoie (323,675 inhabitants). The annual incidence is therefore 3,8/100,000. The mean age is 70 years. In each age class the incidence for women is approximately 3 times that for men. The geographic distribution parallels that of the whole population. There is no seasonal variation of incidence. 9 cases only (15%) could be considered as drug-induced. The prevalence of shallow anterior-chamber (less than 2.2 mm) and Van Herrick sign in the general population shows that the latter sign implies a 50% risk of acute angle closure, and is therefore well suited for the detection of patients at risk. PMID- 2590984 TI - [Evaluation of 100 melanomas of the choroid and ciliary body treated by application of ruthenium (RU 106 Rh 106)]. AB - 100 cases of uveal melanomas, were treated with 106 RU 106 RH beta-brachytherapy, between June 1983 and September 1987. 82 eyes having a follow-up superior or equal to 6 months, were analysed. 13 of these 82 eyes have been enucleated. 2 patients, have died, 2 have at this time, hepatic dissemination. The first 43 patients were analysed at the 18th month after irradiation. The majority of tumors with initial thickness inferior to 5 mm had a regression superior to 50%, at the 18th month. The majority of tumors with initial thickness superior to 5 mm, had a regression inferior to 50%, at the same time. Functional results have also been noticed in this series of 43 eyes, and were satisfactory. PMID- 2590985 TI - [Current diagnostic technics of retinoblastoma (cytology of the vitreous body and marker)]. PMID- 2590986 TI - [Tilted disk syndrome. Symptomatologic aspects and diagnostic problems. Apropos of a case]. AB - The tilted disk syndrome is a frequent congenital abnormality. The case reported here associates tilt of the disk crescent hypopigmentation of inferonasal quadrant and macula ectopy. We study the visual field defects which are attributed to a localized ectatic inferonasal area. We discuss then the opportunity to perform neurological examination. PMID- 2590987 TI - [Late macular complications in a case of artificial lens implant in the anterior chamber in an eye already treated by filtering]. AB - The Author have evaluated a cystoid macular edema after surgery with I.O.L. implantation in anterior chamber in pre-operated eye by antiglaucomatous filtering operation. PMID- 2590989 TI - [Growth hormone in developmental diabetic retinopathy]. PMID- 2590988 TI - [Eye manifestations of Horton's disease]. AB - Ocular complications occurring in temporal arteritis are of different severities. These manifestations of the disease occurred in a population of 57 patients with diagnosis of temporal arteritis, in 16 of them (28%). The diagnosis was suggested by finding an inflammatory syndrome (high erythrocyte sedimentation rate) and confirmed by temporal artery biopsy. In making this diagnosis, it was helpful to find a history of characteristic temporal headaches, neckache, jaw claudication, fever and malaise or weight loss in addition to polymyalgia and polyarthralgia. 6 patients presented with diplopia and different ocular muscle or nerve palsies. The 10 others came for sudden loss of vision due to ischemic anterior or posterior neuropathy and in one case, central artery obliteration. Prompt treatment with steroids gave good results on oculomotor troubles and in preventing the risk of involvement of the fellow eye. But loss of vision did not regress with this treatment. That means the importance in making this diagnosis and starting very promptly this treatment. PMID- 2590990 TI - [Retinal detachment caused by a macular hole in severe myopia: technics of surgical treatment without indentation (analysis of 15 successive cases)]. PMID- 2590991 TI - [Cataract surgery in children. Immediate postoperative equipment. Technical note]. PMID- 2590992 TI - [Hypernegative artificial lenses and macular degeneration related to age]. PMID- 2590993 TI - [Orbital hemangiopericytoma in children]. PMID- 2590994 TI - [Insertion of a negative implant in the anterior chamber in phakic patients]. PMID- 2590995 TI - [Results of myopic keratomileusis without congelation. Retrospective study apropos of 17 cases]. PMID- 2590996 TI - Studies on the human metabolism of iproplatin. AB - We have previously shown that a significant portion of the total platinum in the plasma of patients receiving iproplatin is protein-bound. We have also identified cis-dichloro-bis-isopropylamine platinum(II) (CIP) as a major metabolite of iproplatin. To understand the nature of the bound platinum, we carried out in vitro comparative protein-binding studies for iproplatin and CIP. These studies indicate that when CIP is incubated in plasma, protein binding occurs, with a 2.7 h half-life for the disappearance of CIP; the parent complex does not bind and is stable in plasma for at least 48 h. The time dependence of protein binding with CIP suggests the formation of other chemical species from CIP that may be responsible for the observed protein binding. The results indicate that in patients receiving the drug, the reduction of iproplatin to CIP must take place intracellularly and that CIP or its protein-binding derivatives must efflux from the cells into the plasma. Efflux studies carried out to explore this possibility with cells in the whole blood showed that iproplatin was taken up into cells, but the efflux of protein-binding iproplatin metabolites did not occur. To understand further the nature of the metabolites of iproplatin, we carried out 195Pt-NMR (nuclear magnetic resonance) studies with urine from two patients who received a high dose of iproplatin (500 mg/m2). The predominant signals from the 195Pt-NMR corresponded to the divalent platinum complexes and not to quadrivalent complexes, indicating that the iproplatin metabolites in urine are divalent in nature. PMID- 2590997 TI - Uptake and metabolism of iproplatin in murine L1210 cells. AB - Iproplatin is structurally unique among the platinum (Pt) agents in the clinic because it is a quadrivalent complex. On the basis of the redox parameters for the Pt(IV) and Pt(II) oxidation states in a chloride system, it has been suggested that Pt(IV) complexes will be reduced to Pt(II) complexes in a biological environment. To test this hypothesis, uptake and metabolism studies of [14C]-iproplatin were carried out in L1210 cells. The L1210 cells raised in DBA2/J mice were incubated in vitro with 50 and 100 microM [14C]-iproplatin at 37 degrees C in Hanks' balanced salt solution, and total uptake and radioactivity associated with acid-insoluble fractions were measured for up to 3 h. Under these conditions, the uptake of iproplatin was linear with time and increased with increasing concentrations of iproplatin in the medium. At all times measured, greater than 35% of radioactivity was associated with the acid-insoluble fraction, suggesting binding to macromolecules. The [14C]-labelled compounds in neutralized acid extracts of cells were separated by reverse-phase high performance liquid chromatography (HPLC). Three labelled compounds were detected; based on chromatographic elution times, they appeared to be iproplatin, cis dichloro-bis-isopropylamine platinum(II) (CIP), the reduction product of iproplatin, and a third compound more polar than iproplatin and CIP. The finding of free CIP and the macromolecular binding of radioactivity in the cells suggests that iproplatin is reduced intracellularly. PMID- 2590998 TI - Effect of retinoic acid on human neuroblastoma: correlation between morphological differentiation and changes in plasminogen activator and inhibitor activity. AB - The relationship between plasminogen activator (PA)/plasminogen activator inhibitor (PAI) activity and morphological differentiation was investigated in human neuroblastoma (NB) cells treated with retinoic acid (RA). Conditioned medium from nine NB cell lines and one closely related neuroepithelioma line was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and zymography. All NB cell lines were shown to secrete urokinase (UK)-type PA (mol. wt., 52 kDa), and all except two produced tissue PA (mol. wt., 65 kDa). Identification of the PAs was made based on molecular weight and sensitivity to inhibition by anti-UK and anti-tPA antibodies. Several cell lines expressed PA inhibitory molecules; two molecular-weight forms were observed (35 and 40 kDa) in different cell lines. Complex formation with [125]I-labelled proteases revealed specific binding with UK and trypsin but not thrombin, plasmin, or kallikrein. After treatment for 6 days with 1 microM RA, six of the cell lines exhibited an increase in cell-associated and/or secreted tPA activity, corresponding to morphological differentiation of the cells as manifested by extensive neurite outgrowth. A decrease in UK and UK-complex secretion was observed in several of these cell lines. Three cell lines exhibiting no detectable morphological alterations with RA treatment also showed no dramatic changes in PA/PAI activity. These results suggest that morphological differentiation of NB cells may be associated with alterations in the regulation of PA activity. PMID- 2590999 TI - Effect of lonidamine on the cytotoxicity of four alkylating agents in vitro. AB - We examined the ability of lonidamine, which has been described as an inhibitor of cellular respiration and glycolysis, to enhance the cytotoxicity of alkylating agents to MCF-7 human breast-carcinoma cells. Lonidamine was increasingly cytotoxic to MCF-7 cells with increasing time of exposure. With a 12-h exposure, the IC50 for lonidamine was about 365 microM, and with a 24-h exposure it was about 170 microM. A drug concentration of 250 microM was chosen for use in the drug combination studies. Lonidamine appeared to have a dose-modifying effect on cisplatin (CDDP), producing increasingly supra-additive cell kill with increasing CDDP concentration. When simultaneously incubated with lonidamine for 1 h, 500 microM CDDP yielded a cell kill that was 2 log greater than additive cytotoxicity. Extending the exposure to lonidamine for 12 h after CDDP treatment led to a small, additional aliquot of cell kill of about 2.5-fold over the CDDP concentration range. Lonidamine also appeared to have a dose-modifying effect on melphalan cytotoxicity in the melphalan concentration range of 100-500 microM. Between concentrations of 10 and 100 microM melphalan, the drug combination survival after 1 h exposure fell within the envelope of additivity for the two agents. However, maintaining the presence of lonidamine for an additional 12 h increased the effect such that the combination was supra-additive over the entire concentration range of melphalan. Simultaneous exposure to 4 hydroperoxycyclophosphamide (4-HC) and lonidamine for 1 h resulted in greater than additive cell kill, and extending the lonidamine exposure period such that lonidamine was present during and 12 h after 4-HC treatment further increased this effect. Lonidamine had a moderate effect on the cytotoxicity of carmustine (BCNU) with a 1 h simultaneous exposure; however, this treatment combination reached greater than additive cytotoxicity only at the highest concentration of BCNU tested. Extending the lonidamine exposure time for an additional 12 h resulted in supra-additive cell kill over the BCNU concentration range. Therefore, when lonidamine was present during exposure to the alkylating agent and its presence was then extended for an additional 12 h, a synergistic cell kill was produced with all four alkylating agents tested. PMID- 2591000 TI - Effects of 5-fluorouracil on cytotoxicity and RNA metabolism in human colonic carcinoma cells. AB - The cytotoxicity of 5-fluorouracil (5-FU) is due in part to the incorporation of the base into RNA molecules. We assessed the cytotoxicity of 5-FU in human colonic carcinoma HT-29 cells and examined mRNA activity (measured by protein biosynthesis in vivo and in vitro) and the maturation of rRNA precursors as two possible modes of action of 5-FU. The rRNA processing pathways were studied using rDNA sequences as probes in blot hybridisation protocols and were specific for both the precursors and mature rRNA species of the maturation pathways. The conclusion from the studies was that although differences in mRNA activity were detected in vivo and in vitro, the significance of these changes are as yet unknown. In contrast, the effects on the pre-rRNA processing pathways proved to be highly significant cytotoxic consequences of 5-FU administration. We discuss the implications of this finding for an understanding of the mode of action of the drug and for the future monitoring of tumour sensitivity to 5-FU. PMID- 2591001 TI - Response of human HT-29 colorectal tumor cells to extended exposure to bromodeoxyuridine. AB - Effects of the extended exposure of a human colorectal tumor-cell line (HT-29) to bromodeoxyuridine (BrdUrd) were studied in anticipation of the clinical use of that agent to treat colorectal cancer, particularly as a regionally delivered radiosensitizer. We found that 72-h exposure to a concentration of BrdUrd that is estimated to be locally maintained in the liver (100 microM) was significantly cytotoxic with a 3-log reduction in survival. As measured by GC/MS-SIM method, incorporation of BrdUrd into DNA followed an unexpected time course in that continuous exposure to 10 microM BrdUrd resulted in maximal incorporation at 3 days, after which the extent of incorporated analog fell significantly (despite daily changes of the medium). This finding was apparently due to a greater rate of loss of BrdUrd from the medium at later time points. Flow cytometric analysis using an anti-BrdUrd antibody (IU-4) revealed that antibody binding also peaked and fell off with time. However, at exposure times of greater than 24 h, the timing and extent of this decline were significantly different than had been indicated by the GC/MS method. These results indicate that the quantitative relationship between antibody staining and BrdUrd incorporation changes as drug exposure time increases and that quantitative studies of anti-BrdUrd antibody binding must be interpreted with caution, especially when extended drug-treatment protocols have been used. PMID- 2591002 TI - Pharmacokinetics of busulfan: correlation with veno-occlusive disease in patients undergoing bone marrow transplantation. AB - Busulfan is an alkylating agent that is widely used in preparative regimens for bone marrow transplantation (BMT). We developed a high-performance liquid chromatographic (HPLC) assay for the determination of plasma busulfan concentrations in 30 patients who received oral doses of 1 mg/kg. Concentrations were fit by a one-compartment pharmacokinetic model with first-order absorption. The pattern of absorption and elimination varied widely between patients, with peak concentrations ranging from 1.2 to 10.4 mumol/l (mean, 4.25 +/- 2.49). The elimination half-life ranged from 58 to 433 min (harmonic mean, 140 min). The AUC contributed by a single oral dose ranged from 606 to 5,144 mumol-min/l (mean, 2,012 +/- 1,223). Patients were evaluated for the development of veno-occlusive disease (VOD), a treatment complication that occurs in 20% of patients undergoing BMT and causes 10% of transplantation-related deaths. All six patients who developed VOD had an AUC greater than the mean, and five of them had an AUC that was greater than 1 SD above the mean. The occurrence of VOD was highly correlated with an increased AUC (greater than 1 SD above the mean) (X2 = 18; P less than 0.0001). Using multivariate logistic regression, no other statistically significant pharmacokinetic predictor of VOD was found. The tenfold variability in the busulfan AUC and the statistical association of increased AUC with the development of VOD suggest a possible role for therapeutic monitoring in this setting. PMID- 2591003 TI - Maintenance chemotherapy for childhood acute lymphoblastic leukemia: relation of bone-marrow and hepatotoxicity to the concentration of methotrexate in erythrocytes. AB - To explore the clinical significance of the concentration of methotrexate (MTX) in erythrocytes (E-MTX), 42 boys and 31 girls were studied during maintenance chemotherapy for childhood acute lymphoblastic leukemia for periods of 3-22 months (median, 8 months) at an unchanged dose of MTX. For each study period, a weighted mean of white cell counts (mWBC), absolute neutrophil counts (mANC), and serum aminotransferases (mAT) were calculated, using as weights the intervals from sampling until the next WBC, ANC, or AT determinations were done. In 17 patients who underwent at least six measurements of E-MTX during a period in which the MTX dose remained unchanged for up to 22-months, the median intraindividual coefficient of variation for E-MTX was 10% (range, 5%-22%). For each patient, a mean of all E-MTX values (mE-MTX) during a study period (range, 1 15 measurements; median, 3) was used as an index of the RBC accumulation of MTX at the prescribed dose of MTX. Among 42 patients receiving full-dose MTX (greater than 17.5 mg/m2), the mE-MTX ranged between 3.4 and 9.6 nmol hemoglobin (Hb) (interindividual coefficient of variation, 33%). The mE-MTX was significantly related to the MTX dose (r = 0.45, P = 0.00003). The mWBC and mANC were both significantly related to the mE-MTX (mWBC: r = -0.31, P = 0.004; mANC: r = -0.35, P = 0.02), but not to the dose of MTX (mWBC: r = -0.08, P = 0.25; mANC: r = 0.22, P = 0.08). Each of four patients with a persistent rise in AT above the upper normal limit (40 IU/l) and an mAT of greater than 80 IU/l had an mE-MTX of greater than 6.5 nmol/mmol Hb. Due to its low intraindividual variation, E-MTX may be useful for detecting persistent or intermittent failure of patient compliance. Its prognostic significance and its clinical value in MTX dose adjustment should be explored in prospective studies. PMID- 2591004 TI - Phase II study of mitoxantrone for liver metastases from breast cancer. AB - Mitoxantrone was given to 19 patients with liver metastases from breast cancer and biochemical evidence of liver dysfunction. In all, 2 patients received the drug at a dose of 10 mg/m2 on days 1 and 2 of the first course of treatment; 1 patient was given 9 mg/m2 and 17 received 8 mg/m2. Subsequent courses were given at a dose of 10 mg/m2. Three patients (16%) showed a partial response, with time to progression of between 3 and 7 months. Toxicity was considerable, with myelosuppression being the major problem. PMID- 2591005 TI - Herpes simplex virus, Candida albicans and mouth ulcers in neutropenic patients with non-haematological malignancy. AB - Mouth ulcers are a frequent cause of morbidity in patients rendered neutropenic as a result of chemotherapy. We report here a series of 28 such patients from whom swabs were taken for viral isolation and mycological culture. In 13 patients, herpes simplex virus (type I) was isolated and in 17 patients Candida albicans was cultured. Both organisms were isolated in 9 patients. Our results suggest that both a viral and fungal element may be important in the aetiology of oral ulceration and that antiviral and antifungal agents may each have a role in the prophylaxis and treatment of such patients. PMID- 2591007 TI - Retinoic acid inhibits the fixation of initial transformational damage in X irradiated Balb/3T3 mouse fibroblasts in vitro. AB - We have examined the effects of all-trans retinoic acid (RA) on confluent holding recovery (cell survival) and on the fixation of initial transformational damage expressed as the ultimate yield of transformed foci following X-irradiation of density-inhibited cultures of Balb/3T3 cells. Non-cytotoxic concentrations of RA suppressed both recovery of potentially lethal damage and neoplastic transformation in a dose-dependent manner when added for 24 h during post irradiation confluent holding after a dose of 5 Gy. At 100 microM, RA inhibited the fixation of initial transformational damage by 80%. These findings are discussed in terms of the hypothesis that retinoids may allow a selective enhancement of the inactivation of certain irradiated tumor cells in vivo while reducing the risk of secondary malignancies in successfully treated patients. PMID- 2591006 TI - A carcinogenesis- and tumorigenesis-associated rat fetal protein: an immuno histochemical and immuno-biochemical study utilizing a new monoclonal antibody, MOFP. AB - An oncofetal protein (OFP), which is a potential marker for carcinogenesis and tumorigenesis, was evaluated with monoclonal antibodies shown to be specific for the antigen. Treatment of partially hepatectomized rats with a single non necrogenic dose of diethylnitrosamine induced OFP in the liver. Its concentration, as measured by a dual immuno/bioassay, increased steadily over a 5 week period of observation before reaching a constant level. Immunohistochemical localization of OFP in liver sections from rats treated with N-nitroso-N-diethyl nitrosamine showed that the factor was primarily localized to the cell cytoplasm in cells of most of the altered hepatic foci although some of this shedding antigen was also extracellular. Monoclonal antibody 17-1A specific for 17-1A antigen, an established surface marker for adenocarcinomas of the gastrointestinal tract, showed a similar distribution in liver from the carcinogen-treated rats, but localized to the cell membrane and cytoplasm. Scattered cells surrounding the altered hepatic foci were also positive for both monoclonal antibodies. Immunolocalization studies showed fetal rat liver and hepatoma were positive for OFP but adult normal or regenerating liver was negative. It was not detected in cells which morphologically could be classified as oval cells. As assessed by immuno/bioassay, the OFP released to the peripheral blood (plasma) of hepato-carcinogen-treated rats increased for 3 weeks, before undergoing a transitory decrease. Circulating antibodies specific for the factor were detected in the blood around 3-5 weeks post-treatment. Development of Western blots of the OFP with antiphosphotyrosine IgG indicates that the marker protein contains phosphotyrosine. PMID- 2591008 TI - Binding of 7H-dibenzo[c,g]carbazole to polynucleotides and DNA in vitro. AB - The N-heterocyclic aromatic pollutant, 7H-dibenzo[c,g]carbazole (DBC), is a potent carcinogen having both local and systemic effects. The overall objective of this research was to investigate the nature of the covalent binding of DBC with nucleic acids in vitro. DBC was shown to bind to polynucleotides, RNA and DNA in an in vitro rat or hamster microsomal enzyme assay, exhibiting a preferential binding to polyguanylic acid (poly[G]). Benzo[a]pyrene (BaP) binding to these same nucleic acids was determined simultaneously and was approximately 10-fold higher than DBC binding under identical experimental conditions. DBC nucleic acid binding was shown to be dependent upon the presence of a microsomal activating system, the results being similar for rat or hamster liver microsomes. This microsome-dependent binding was unaffected by the addition of epoxide hydrase activity modifiers but was almost completely inhibited by alpha naphthoflavone. The nature of DBC-nucleic acid binding was investigated using fluorescence spectroscopy. Benzo[c]carbazole and 5,5,6,6 tetrahydrodibenzo[c,g]carbazole were synthesized as representatives of the effect of disruption of the DBC pi-electron system on fluorescence excitation and emission. DBC-poly[G] adducts were isolated from binding assay mixtures and separated by HPLC. Results indicated that there are at least three different DBC poly[G] adducts formed in vitro. The emission spectra of isolated adducts were similar in shape to that of DBC; however, the adduct spectra were shifted 5-10 nm toward longer wavelengths. This suggests that the bound DBC species have intact pi-electron systems. Results are consistent with binding through the nitrogen position as well as binding through the 1,2,3,4-ring of the molecule. PMID- 2591009 TI - Ketonitrosamines as metabolites of methyl-n-amylnitrosamine (MNAN) and its hydroxy derivatives in the rat. AB - In a previous study of the metabolism of methyl-n-amylnitrosamine (MNAN) in the rat, 2- to 5-hydroxy-MNAN (HO-MNAN) were provisionally identified as metabolites and the identity of 4-HO-MNAN was confirmed by mass spectrometry. We now describe syntheses and mass and other spectra for 2- to 5-oxo-MNAN. Two previously unidentified MNAN metabolites were shown to be 3- and 4-oxo-MNAN. In addition to 4-HO-MNAN, we confirmed 3-HO-, 4-oxo- and (less certainly) 2-HO-MNAN as urinary MNAN metabolites by GLC-MS of HPLC fractions. Analysis with and without beta glucuronidase treatment showed that the urinary HO-MNANs occurred as their beta glucuronides. MNAN (25 mg/kg injected i.p.) had a blood half-life of 21 min in adult male rats. The blood also contained 4-HO- and 4-oxo-MNAN, which showed maximum levels that were 13 and 26% respectively of that for MNAN, and were cleared more slowly than MNAN. On incubation for 3 h with MNAN, rat esophagus produced 3- and 4-oxo-MNAN in yields that were 5% of those for the corresponding HO-MNANs. For MNAN metabolism, the 4-oxo-/4-HO-MNAN ratio of metabolites was 5% for adult rat liver and was 22% for adult hamster liver and 9-day-old rat liver. On incubation with 4-HO-MNAN for 3 h, oxidation to 4-oxo-MNAN was 16-25% for adult hamster or 9-day-old rat liver slices and for adult hamster liver homogenate. Homogenate activity was concentrated in the microsomal fraction, for which NAD was a more effective co-factor than NADP. A bacterial alcohol dehydrogenase oxidized 4-HO- to 4-oxo-MNAN in 38% yield/3 h. None of these preparations oxidized 2-HO- to 2-oxo-MNAN. It was concluded that 3- and 4-oxo MNAN were metabolites of MNAN, apparently (for 4-oxo-MNAN) via HO-MNAN oxidation by a microsomal NAD-dependent enzyme, that 4-HO- and 4-oxo-MNAN formation was a major route of MNAN metabolism, and that 4-oxo-MNAN might play a role in MNAN carcinogenesis. PMID- 2591010 TI - Monoclonal antibodies to 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) and their use in the analysis of well-done fried beef. AB - Four monoclonal antibodies, PhIP-1, -2, -3 and -4, have been produced that bind to PhIP (2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine), a mutagenic aromatic amine produced in meat by cooking. The immunogen was an analog of PhIP conjugated to a carrier protein through the 2-amino group of PhIP, leaving the pyridine and phenyl rings unmodified. The antibodies show a range of binding specificities for PhIP and its structural analogs, with PhIP-1 being the most highly selective, requiring the entire PhIP molecule with the exception of the exocylic amino group to be present for recognition. A competition enzyme linked immunosorbent assay (ELISA) incorporating these antibodies was developed and applied to the analysis of fried meat extracts differing in mutagen content. In extracts of fried beef, more PhIP-like material was found than would be expected based on chemical estimates of the amount of PhIP, suggesting that frying produces other compounds that are structurally similar to PhIP. These PhIP-like compounds were separated from PhIP using HPLC. Addition of creatinine to the beef prior to frying increased both the mutagenicity of the extracts and the amount of PhIP-like material. Microwave pre-treatment prior to frying reduced both immunochemical reactivity and mutagenicity. PMID- 2591011 TI - Antagonistic effect of diethylmaleate on the promotion of forestomach carcinogenesis by butylated hydroxyanisole (BHA) in rats pretreated with N-methyl N'-nitro-N-nitrosoguanidine. AB - The effects of diethylmaleate (DEM), previously demonstrated to inhibit butylated hydroxyanisole (BHA)-induced forestomach hyperplasia, on BHA promotion of forestomach carcinogenesis in rats pretreated with N-methyl-N'-nitro-N nitrosoguanidine (MNNG) were examined. Groups of male 6-week-old F344 animals were given a single i.g. administration of 150 mg/kg body weight MNNG and starting 1 week later administered powdered diet containing 1% BHA plus 0.2% DEM, 1% BHA, 0.2% DEM or basal diet alone for 51 weeks. Further groups of rats were treated with 1% BHA plus 0.2% DEM, 1% BHA, 0.2% DEM or basal diet alone without MNNG pretreatment. Histopathological assessment of lesions at week 52 revealed enhancement of MNNG-initiated papilloma (100 versus 50%) and squamous cell carcinoma (100 versus 0%) development by BHA as compared to controls. Additional treatment with DEM, however, significantly reduced the relative incidences of carcinoma in situ (0 versus 35.7%) and squamous cell carcinoma (35.7 versus 100%), as well as BHA-induced forestomach hyperplasia with or without prior MNNG treatment. The results thus clearly demonstrate that DEM acts as a potent antagonist to BHA-promotion of rat forestomach carcinogenesis. PMID- 2591012 TI - Comparative study of diethylnitrosamine-initiated two-stage hepatocarcinogenesis in C3H, C57BL and BALB mice promoted by various hepatopromoters. AB - The comparative inducibility of enzyme-altered islands (EAIs) by diethylnitrosamine (DEN) and their responsiveness to hepatopromoters belonging to different classes were studied in C3H/HeN (C3H), C57BL/6N (C57) and BALB/cA (BALB) mice. Male mice were given an i.p. injection of DEN (20 micrograms/g body weight) after partial hepatectomy at 6 weeks of age and then fed either basal diet or diet containing phenobarbital (PB) (500 p.p.m.), clofibrate (CF) (1000 p.p.m.) or ethynyl estradiol (EE) (10 p.p.m.). The numbers and size distribution of EAIs were assessed after the mice were killed at week 20, utilizing stereological methods. In the groups receiving DEN but no promoter, the number and mean size of the lesions were far larger in the C3H mice than in the other strains. Under the promoting pressure of PB, the growth of EAIs in C3H and BALB were accelerated remarkably, but those of C57 mice only slightly. Interestingly, in BALB the number of EAIs was much fewer than those of C3H in spite of their good sensitivity to PB, suggesting that BALB was refractory to the initiation process by DEN. A promoting effect for CF could only be demonstrated for the C3H strain and EE as the dose used inhibited the development of EAIs in all the strains. The experimental data thus indicate that interstrain differences in two stage hepatocarcinogenesis among mice with different genetical backgrounds may exist, either in initiation or promotion, or in both processes. PMID- 2591013 TI - Detection of distinct transforming genes in X-ray induced tumors. AB - DNAs from mouse skin tumors (papillomas, squamous cell carcinomas, basal cell carcinomas and pilomatrixomas) initiated with X-irradiation and promoted with 12 O-tetradecanoyl-phorbol-13-acetate (TPA) demonstrated dominant transforming activity by the production of transformed foci in the mouse recipient line, NIH3T3. Dominant transforming activity was not found in DNA isolated from normal mouse epidermis or from the corresponding liver. The NIH3T3 transformants induced with squamous cell carcinoma DNA grew in soft agar and formed tumors in nude mice. Southern blot analysis of primary NIH3T3 transformant DNAs carrying oncogenes from radiation-initiated squamous cell carcinomas indicated that the oncogenes responsible for the transformation of the recipient cells were not Ha ras, Ki-ras or N-ras genes, nor were they erbB, B-lym, met, neu or raf. The data presented indicate that DNAs from radiation-initiated mouse skin tumors contain dominant transforming genes that are detectable by DNA-mediated gene transfer. The oncogene sequences activated in these radiation-initiated tumors are distinct non-ras transforming genes. PMID- 2591014 TI - Pentapeptide inhibitor of epidermal mitosis: production and responsiveness in cultures of normal, transformed and neoplastic human keratinocytes. AB - A pentapeptide, pyroGlu-Glu-Asp-Ser-GlyOH, was previously isolated from mouse skin and shown to inhibit reversibly proliferation of murine keratinocytes, both in intact skin and in culture. In the present report we have shown that proliferation of normal human keratinocytes in culture is also inhibited by the pentapeptide, whether the cells are grown under standard conditions or prevented from stratifying in medium containing a low concentration of calcium ions. An SV40-transformed line of human keratinocytes, SVK14, was completely insensitive to the pentapeptide and a line derived from a squamous cell carcinoma of the oral cavity, SCC-9, was less sensitive than the normal cells. The effect of the pentapeptide on terminal differentiation was determined by measuring the proportion of cells expressing involucrin after a single dose or repeated doses of the pentapeptide: no consistent change in the number of terminally differentiating cells was observed. Cell extracts and conditioned medium from all three cell types contained the epidermal pentapeptide, suggesting a role for the peptide in both autocrine (normal keratinocytes) and paracine (SVK14, SCC-9) growth control. A proportion of the pentapeptide isolated from conditioned medium was phosphorylated; since it was as active as the non-phosphorylated form, when assayed on mouse epidermis, the role of phosphorylation remains to be determined. PMID- 2591015 TI - Modifying effects of simultaneous treatment with butylated hydroxyanisole (BHA) on rat tumor induction by 3,2'-dimethyl-4-aminobiphenyl, 2,2'-dihydroxy-di-n propylnitrosamine and N-methylnitrosourea. AB - The modifying effects of concurrent treatment with high or low doses of butylated hydroxyanisole (BHA) on wide-spectrum carcinogen-induced carcinogenesis were studied in male F344 rats. Groups of 20 animals were treated with 2 or 0.04% BHA for 24 weeks. Starting 2 weeks after the commencement of BHA treatment, they were given s.c. injection of 50 mg/kg body weight 3,2'-dimethyl-4-aminobiphenyl (DMAB) once a week, i.g. administrations of 200 mg/kg body weight 2,2'-dihydroxy-di-n propylnitrosamine (DHPN) once every 2 weeks, or i.p. injection of 15 mg/kg body weight N-methylnitrosourea (MNU) once every 2 weeks for 22 weeks. Further groups of rats were treated with DMAB, DHPN, MNU, or 2 or 0.04% BHA alone. All surviving animals were killed 24 weeks after the beginning of the experiment and the target organs examined histopathologically. The BHA treatment dose-dependently decreased the incidence of DMAB-induced liver preneoplastic lesions but was associated with significant tumor induction in the forestomach (papillomas, 40%, P less than 0.01) and urinary bladder (papillomas, 53%, P less than 0.001; carcinomas, 80%, P less than 0.001), where no lesions were observed in the group given only DMAB. Concurrent administration of 2% BHA also significantly inhibited the development of alveolar hyperplasia (P less than 0.001) of the lung in DHPN-treated animals, while enhancing induction of forestomach papillomas (P less than 0.05) and simple hyperplasia in the urinary bladder. Neither MNU nor 2% BHA alone induced forestomach carcinoma or papillary or nodular hyperplasia (PN hyperplasia) in the urinary bladder. However, these lesions were observed in 100% (P less than 0.001) and 55% (P less than 0.001) of animals respectively, receiving the two compounds in combination. These results demonstrated that concurrent treatment with BHA not only inhibits but can also strongly enhance carcinogenesis depending on the organ, irrespective of whether the carcinogens act directly or require metabolism. The finding that BHA potently modified carcinogenesis at 0.04% in diet, 1/50 of the carcinogenic dose, suggests that actual dietary levels close to the human situation might play a significant role in tumor development in man. PMID- 2591016 TI - Cell specificity for the pulmonary metabolism of tobacco-specific nitrosamines in the Fischer rat. AB - The activity and distribution of the metabolic pathways of 4-(methylnitrosamino) 1-(3-pyridyl)-1-butanone (NNK), its major metabolite 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanol (NNAL) and the structurally related nitrosamine, N' nitrosonornicotine (NNN) were examined in pulmonary cells from F344 rats in order to investigate the mechanisms by which NNK and NNAL, but not NNN, cause lung tumors. The tritium labeled nitrosamines were incubated with Clara cells, alveolar macrophages, alveolar type II cells, or small cells and metabolites were analyzed by HPLC. O6-Methyl-guanine (O6MG) formation was also quantified in the cells incubated with NNK. Clara cells metabolized all compounds more extensively than the other cell types. Total alpha-hydroxylation, carbonyl reduction to NNAL, and pyridine N-oxidation in cells incubated with NNK, as well as concentrations of O6MG in DNA were higher in Clara cells than in other cell types. Carbonyl reduction of NNK predominated over the other metabolic pathways in all cell types. The high activity for alpha-hydroxylation of NNK in Clara cells is consistent with previous studies which proposed that the cell specificity for O6MG formation and the accumulation of this adduct during low-dose exposure to NNK may stem from the presence of a high affinity pathway in Clara cells for NNK activation. Metabolism of NNAL by alpha-hydroxylation, and by reconversion to NNK followed by alpha-hydroxylation were observed. Total alpha-hydroxylation of NNAL was less extensive than alpha-hydroxylation of NNK. NNN was metabolized by both the 2'- and 5'-alpha-hydroxylation pathways. 2'-Hydroxylation of NNN produces the same DNA pyridyloxobutylating agent as does methyl hydroxylation of NNK. However, NNN is not a methylating agent and does not induce lung tumors in rats. Metabolism of NNN by 2'-hydroxylation was, depending on cell type, 41-85% as extensive as total alpha-hydroxylation of NNK, indicating that the rates of formation of the DNA pyridyloxobutylating agent were similar from NNN and NNK. The results of this study demonstrate that Clara cells have a high capacity to metabolically activate NNK, NNAL and NNN and provide further support for the hypothesis that DNA methylation of pulmonary cells is important in NNK carcinogenesis. PMID- 2591017 TI - Modulation of lung tumor development in mice with the soybean-derived Bowman-Birk protease inhibitor. AB - Male strain A mice were treated with a single i.p. injection of 3 methylcholanthrene (MCA). Four months later, the number of lung tumors was counted. In mice treated three times a week, for 8 weeks, with crude soybean extract containing the Bowman-Birk protease inhibitor (BBI), the number of lung tumors was significantly lower than in control animals receiving carcinogen treatment only (40-70% of controls). On the other hand, treatment initiated 8 weeks after MCA only had no effect on tumor development. A reduction in the number of lung tumors was also found in animals treated i.p. or orally with purified BBI three times a week for 8 weeks following MCA administration. It is concluded that BBI is capable of partially blocking the development of lung tumors in mice. PMID- 2591018 TI - Influence of creatine, amino acids and water on the formation of the mutagenic heterocyclic amines found in cooked meat. AB - Creatine or one of 15 amino acids were mixed with minced pork before broiling at 200 degrees C. Total mutagenic activity and reversed-phase HPLC-separated mutagenicity profiles were determined for the crust and pan residue of all samples and also in the aerosol fraction of the smoke formed during cooking of the creatine-fortified samples. Addition of 5% (w/w) creatine increased the total mutagenicity 4-fold without changing the mutagenicity profile of either crust, pan residue or aerosol. Amino acid addition (1% w/w) increased the total mutagenicity between 1.5 (lysine) and 43 times (threonine). In most cases the mutagenicity profiles of crust and pan residues were changed by amino acid addition. Dry-heated mixtures of amino acids and creatine were all mutagenic with a 250-fold range between the amino acids. The production of known food mutagens in these mixtures was analyzed by LC-MS of HPLC-fractionated mutagenic peaks. Serine, threonine, phenylalanine, alanine, leucine and tyrosine were all shown to give rise to one of the known food mutagens 2-amino-3,8-dimethylimidazo[4,5 f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or 2-amino-trimethylimidazopyridine (TMIP). Lyophilized and subsequently fried meat patties and a heated powder of lyophilized meat juice were both mutagenic, with mutagenicity profiles similar to the regular meat crust, showing that water is not a prerequisite for mutagen formation in meat. MeIQx, 2-amino-3,4,8 trimethylimidazo[4,5-f]quinoxaline (4,8-di-MeIQx) and PhIP were shown, by LC-MS, to be present in the dry-heated meat juice. It is concluded that creatine and free amino acids are the main reactants of the mutagen-forming reactions that occur during frying of meat. Creatine is probably a necessary part of all of these reactions; what specific compounds are formed in each case therefore depends upon the levels in the meat of certain free amino acids and their interactions with other, as yet unknown, compounds in the meat. PMID- 2591019 TI - In vivo inhibition of N-nitrosodimethylamine metabolism by 4-methylpyrazole: a model for endogenous nitrosation. AB - The endogenous formation of N-nitrosodimethylamine (NDMA) was investigated in the ferret by inhibiting metabolism and monitoring urinary NDMA levels. The addition of 1.0 mg/ml of 4-methylpyrazole (4-MP) to the drinking water was sufficient to allow a 13% urinary recovery of a 4.0 nmol oral dose of NDMA to be made in 24 h. Without 4-MP, no NDMA could be detected in urine. There was no detectable urinary NDMA when dimethylamine (DMA) alone was given but when as little as 5 mumol of nitrite and 0.75 mmol of DMA were given, the urine contained approximately 0.3 nmol NDMA/day. Nitrite doses of 0-100 mumol along with 0.75 mmol of DMA resulted in a dose-dependent excretion of less than 0.1-2.5 nmol NDMA/day. When 10 mumol of aminopyrine was substituted for DMA and 40 mumol of nitrite given, the excretion of NDMA was 10 nmol day. Administration of ascorbic acid inhibited NDMA excretion and thiocyanate increased NDMA formation. Consumption of foods containing trace amounts of NDMA resulted in the excretion of NDMA but in most cases at levels that were lower than those ingested in the food. These data suggest that mumol amounts of nitrite can result in the endogenous formation of nmol amounts of NDMA in the acidic environment of the stomach. It also suggests that short-term ingestion of 4-MP might be an approach to studying the possible endogenous formation of NDMA in humans. PMID- 2591020 TI - Placental form of glutathione S-transferase in normal and diseased human uterine cervical mucosa. AB - Expression of the human placental form of glutathione S-transferase (GST-pi), an enzyme proposed as a marker for human and experimental neoplasia, was immunohistochemically evaluated in 51 samples of 'normal' and diseased adult human uterine cervix. Five fetal uteri were also studied. GST-pi positivity was detected in 54, 92, 95 and 83% of the 'normal', non-neoplastic, cervical intra epithelial neoplasia (CIN) and cancer cases respectively. All five fetal uteri and the positive 'normal' adult cases presented cells immunostained for GST-pi throughout the thickness of the mucosa, including the basal layer. Some non neoplastic conditions like inflammation, repair and metaplasia and some dysplastic and neoplastic lesions showed areas of positively stained cells within an otherwise negative tissue, indicating a phenotypic heterogeneity regarding the enzyme expression. Our results confirm that GST-pi has a fetal character and indicate that it may appear in the adult cervical squamous epithelia under 'normal' or pathological conditions not necessarily linked to the process of carcinogenesis. Therefore it cannot be used as a marker for cervical epithelial neoplasia. PMID- 2591021 TI - Mutations induced by aminofluorene-DNA adducts during replication in human cells. AB - To gain insight into the mechanisms by which carcinogens induce mutations in human cells, we treated a shuttle vector, pZ189, carrying the supF gene as the target for mutations with N-acetoxy-N-trifluoroacetyl-2-aminofluorene (N-AcO-TFA AF). The plasmids were allowed to replicate in human cell line 293, and the progeny plasmids were examined for the frequency and kinds of mutations induced in supF, as well as their specific location in the sequence of the supF gene. The plasmids were reacted with N-AcO-TFA-AF so as to obtain the deacetylated adduct N (deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF), the principal adduct formed in DNA when mammalian cells are exposed to reactive derivatives of 2 acetylaminofluorene (AAF), including N-acetoxy-2-acetylaminofluorene. The results showed there was a linear relationship between the number of dG-C8-AF adducts per plasmid and the frequency of supF mutants induced. DNA sequencing of 47 independent mutants obtained from doses of N-AcO-TFA-AF that increased the frequency of mutants 9-15 times the background frequency and three independent mutants from lower doses showed that 92% contained point mutations, i.e. changes affecting one, or two, or three nearby bases, and that all of these point mutations involved G.C base pairs. Ninety eight percent of the point mutations were base substitutions, predominantly G.C----T.A transversions. 46% of these mutations occurred at four out of the 85 bp in the target gene (hot spots). The most prominent mutation hot spot was also the most prominent hot spot for adduct formation as judged by the frequency of termination of in vitro polymerization by the Klenow fragment on N-AcO-TFA-AF-treated plasmids. PMID- 2591022 TI - Genotoxicity of 1- and 2-nitropropane in the rat. AB - 2-Nitropropane (2-NP) is a rat liver carcinogen, whilst the 1-isomer is non carcinogenic in rodents. Although DNA repair tests in the rat liver discriminated clearly between the carcinogenic and the non-carcinogenic isomer, uniformly negative results have been published for the mouse bone marrow micronucleus test (BMMN test) with both isomers. Therefore, the latter assay did not discriminate between the carcinogenic and the non-carcinogenic isomer. To investigate whether this is due to endpoint specificity or organospecificity of 2-NP, studies were carried out in the rat in which micronucleus induction (bone marrow and liver) and unscheduled DNA synthesis (UDS) induction (liver) were measured after oral treatment with either nitropropane isomer. 2-NP induced UDS in the liver whilst the 1-isomer was negative, thus confirming the published studies. In the BMMN test, occasional small increases in the incidence of micronuclei were found for both compounds, but results were interpreted as negative after considering the control background data and the lack of reproducibility. By contrast, the liver micronucleus test revealed a clastogenic effect of 2-NP in the liver. This indicates that 2-NP induces chromosome aberrations as well as DNA repair in vivo, but it seems to act organospecifically. For 1-NP a slightly increased incidence of micronuclei was found in the liver, which was accompanied by a markedly increased mitotic index. It therefore remains questionable as to whether this increased micronucleus frequency for 1-NP is an indicator of a clastogenic effect, or whether it is caused by an increased cell proliferation induced by 1 NP. Consequently, it is too early to conclude whether the liver micronucleus assay is able to discriminate between the carcinogenic and non-carcinogenic isomer. However, the results provide further evidence that bone marrow assays are insufficient for the detection of all genotoxic carcinogens in vivo. This indicates the need for analysing a second tissue, particularly when negative bone marrow results have been obtained with in vitro genotoxins. PMID- 2591023 TI - Cytogenetic effects caused by phorbol ester tumor promoters in HeLa cells: mechanistic aspects. AB - The effect of the convertogenic ('first-stage') tumor promoter TPA (12-O tetradecanoylphorbol-13-acetate) and the non-convertogenic ('second-stage') tumor promoter RPA (12-O-retinoylphorbol-13-acetate) on chromosomes was investigated in HeLa cells which have previously been shown to exhibit a radiomimetic response to TPA. As in the case of mouse keratinocytes, only TPA had a significant clastogenic activity at non-cytotoxic concentrations ranging from 10(-8) to 10( 6) M measured after 24 and 48 h. The values observed with RPA did not differ significantly from values observed in the presence of the solvent (acetone, 0.2%). The response to TPA was saturable with respect to the dose of TPA. The chromosomal aberrations (mostly gaps and breaks) were predominantly of the chromatid type. Isochromatid aberrations were caused by a 24 or 48 h treatment with 10(-6) M TPA. The aberrations appear as early as 6-8 h after TPA application, i.e. as soon as the cells have recovered from TPA-induced inhibition in G2-phase. Even a 30 min exposure to 10(-7) M TPA gives the same yield of aberrations as longer treatment, i.e. the response to TPA is 'saturable' with respect to time. Both TPA and the non-clastogenic RPA cause a temporal G2-delay thus indicating that the G2-inhibition is not related to induction of chromosomal aberrations by TPA. The data are consistent with the hypothesis that TPA induces chromosomal aberrations via a receptor-mediated pathway. PMID- 2591024 TI - Characterization of the induction of ornithine decarboxylase activity by benzoyl peroxide in SENCAR mouse epidermis. AB - The induction of epidermal ornithine decarboxylase (ODC) activity by benzoyl peroxide (BPO) was characterized to evaluate the usefulness of this effect as a short-term marker of BPO-induced mouse skin tumor promotion. The maximal induced levels of ODC specific activity, after a single topical dose of BPO, were greater than 2-fold higher when a cold scraping method was used to prepare epidermis rather than the commonly used heat treatment method. Therefore, the cold scraping method was used for all the work reported here. Application of a single 20 mg dose of BPO to the dorsal skin of SENCAR mice caused a relatively small induction of epidermal ODC activity, to a level less than 1/40 that induced by a single 2 micrograms dose of 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, the time-courses of induction were different after single doses of TPA and BPO, with peak activities observed at approximately 6 and approximately 24 h after treatment respectively. In contrast, after a total of five 20 mg doses of BPO were topically applied (one dose every 2 days), ODC activity was transiently induced to an average level greater than 15 times after a single dose. Additionally, on this dosing regimen, the peak of ODC activity shifted to approximately 4 h after the last treatment, so that the time-course of ODC induction resembled that after multiple applications of TPA. The extent of epidermal ODC induction by BPO was found to be a complex function of the frequency of dosing and the number of treatments. However, when BPO treatments were administered from 1 to 7 days apart, similar maximal induced levels of ODC activity were eventually achieved after application of multiple doses. Importantly, the dose-response for the induction of ODC activity by five doses of BPO (applied one dose every 2 days) was highly correlated with published data on the dose-response for tumor promotion by this organic peroxide, indicating that ODC induction is a good short-term marker of BPO-induced tumor promotion in SENCAR mice. PMID- 2591025 TI - Inhaled cigarette smoke induces preneoplastic changes in rat tracheal epithelial cells. AB - Rats were exposed 6 h/day, 5 days/week for 5 weeks to levels of cigarette smoke designed to deposit amounts of particulate per gram of lung similar to those experienced by a heavy smoker. Tracheal epithelial cells were isolated and examined in culture for the presence of preneoplastic variants. Two- to three fold increases in the frequency of variants were observed in cells isolated from smoke-exposed animals compared to those from air-exposed controls. These results provide an estimate of the frequency of cigarette smoke-induced initiation events in respiratory epithelium that will be useful in further defining the role of cigarette smoke in the development of lung cancer. PMID- 2591026 TI - Influence of the degree of DNA modification on the immunochemical determination of cisplatin-DNA adduct levels. AB - Two different enzyme-linked immunosorbent assays (ELISAs) are used for the sensitive determination of cisplatin-DNA adducts in, for example, blood cells of cisplatin-treated cancer patients. Poirier et al. determined the adducts in native DNA with an antiserum raised against highly modified cisplatin-DNA. Fichtinger-Schepman et al. assayed the various adducts after chromatography of enzymatically digested DNA samples, with antibodies raised against synthetic haptens mimicking the Pt-containing digestion products. In identical human samples analysed by both methods, 14- to 300-fold higher adduct levels were found with the Fichtinger-Schepman method. Adduct levels in organ samples of cisplatin treated rats and mice allowed comparison of both ELISAs with independent Pt assays (atomic absorption spectroscopy, AAS). AAS data confirmed the results of the Fichtinger-Schepman assay, whereas ELISAs according to Poirier showed differences up to a factor of 1000. Analysis of cisplatin adducts in in vitro modified DNA revealed that the Poirier antibodies yield correct estimates with highly modified DNA, but fall short at low platination levels: no adducts could be detected in samples modified to a level similar to that found in blood cells from cisplatin-treated patients. The positive responses obtained with samples of such patients, who had been treated repeatedly, might be explained if cisplatin adducts are preferentially formed around persistent lesions from the previous treatments. PMID- 2591027 TI - Glutathione S-transferases in normal and cancerous human colon tissue. AB - In order to evaluate the role of the placental form of glutathione S-transferase (GST-Pi) as a tumour marker, activity and composition of GSTs from human colon were investigated. GSTs were purified from normal colon mucosa and from colonic tumours by affinity chromatography on glutathione-agarose. After SDS-PAGE or isoelectric focusing these purified preparations revealed only one band that comigrated with GST-Pi from human placenta. A monoclonal antibody (mAb) very specific for GST-Pi was developed and characterized. On immunoblot this mAb stains purified GST from normal and diseased colon tissue. GST activity was significantly higher in most cancerous (247 +/- 38 nmol/min/mg protein; n = 7), compared with the corresponding normal tissues (171 +/- 18 nmol/min/mg protein; n = 7). In colon from patients without large bowel malignancies GST-Pi is also by far the most prominent isoform detectable. In conclusion, both normal and tumorous colon tissue predominantly express GST-Pi and therefore GST-Pi is not suitable as a tumour marker for colonic carcinomas. However, the increased GST-Pi levels in colonic tumours could possibly contribute to the relatively high resistance to anti-cancer drugs. PMID- 2591028 TI - Increased urinary nitrosamine excretion in patients with urinary diversions. AB - Tumor development at the site of ureterointestinal anastomosis is a recognized complication in patients with continent urinary diversions. Aerobic cultures of rectal urine samples from 30 patients with urinary diversions (26 ureterosigmoidostomies, two colon conduits, one ileal conduit and a Gersuny bladder) showed a complex bacterial flora containing nitrate-reducing organisms (Escherichia coli, Proteus and Klebsiella spp.). In comparison to normal bladder urine samples from control volunteers (n = 20), rectal urine samples from ureterosigmoidostomy patients (n = 26) showed a significant decrease (P less than 0.0001) in urinary nitrate (0.93 +/- 0.39 versus 0.27 +/- 0.23 mmol/l), a significant increase (P less than 0.0001) in urinary nitrite (not detected versus 29.24 +/- 39.93 mumol/l) as well as a significant increase (P = 0.013) in urinary N-nitroso compound excretion (57.33 +/- 33.87 versus 93.96 +/- 65.76 nmol/l). Significant increases were also found for the urinary excretion of individual volatile and non-volatile N-nitroso compounds, clearly demonstrating a bacterially mediated in vivo formation of N-nitroso compounds in the 'colon' bladders of patients with urointestinal diversions that may be an important etiological risk factor for colon carcinogenesis in this patient group. PMID- 2591029 TI - Possible involvement of beta-endorphin in the deteriorating effect of arginine vasopressin on burn shock in rats. AB - The effect of intracerebroventricular injections of arginine vasopressin (AVP) on burn shock in the rat and its possible mechanism were explored in this study. AVP was administered intraventricularly at 30 min intervals (50 ng) in the burned rats. The arterial pressure and electrocardiogram (ECG) were recorded with a multipurpose polygraph before and after burn. Compared with the control, the MAP of the rats in the AVP group was elevated at the initial stage and fell dramatically at the late stage of burn shock with a higher mortality. The ECG of the rats in the AVP group also displayed earlier changes such as elevation of S-T segment, inversion of T wave, and ventricular fibrillation. These findings suggest an unfavorable role of AVP in burn shock. The plasma, hypothalamic, and anterior and posterior pituitary levels of beta-endorphin 3 hr after burn were measured by radioimmunoassay. The increased level of beta-endorphin in the plasma after AVP treatment indicates the possible involvement of beta-endorphin in the deteriorating effect of AVP on burn shock. PMID- 2591031 TI - Changes in hemorheology in patients with sepsis or septic shock. AB - We studied hemorheological variables in ten consecutive patients with sepsis or septic shock. One patient with sepsis, eight with septic shock, and one with the toxic shock syndrome were included. The patients were studied during the first 3 days and the eighth day of their illness. All patients except one survived 1 week. Final outcome showed a 50% mortality. A decrease in low shear blood viscosity of red blood cells (RBC) suspended in plasma was observed. This indicates a decrease in RBC aggregation. These changes persisted during the first week. The decrease in RBC aggregation occurred despite a normal plasma viscosity. No correlations were found between the reduction in RBC aggregation and changes in blood chemistry, amounts of dopamine or plasma administered, or with the APACHE II score. A decrease in RBC deformability was observed, due to changes in the RBC membrane. After 1 week, these changes had disappeared. The change in RBC deformability during the study period was significantly related to changes in the amount of dopamine administered. PMID- 2591030 TI - Prevention of the toxic action of tumor necrosis factor by cyclooxygenase inhibitor and leukopenia. AB - The interactions between leukopenia induced by vinblastine and the cyclooxygenase inhibitor indomethacin on the toxicity of tumor necrosis factor (TNF) were studied. When indomethacin was injected 60 min before the administration of recombinant TNF, it provided significant protection against rapid killing by TNF; leukopenia also prevented the toxic action of TNF. However, their inhibition of the activity of TNF was not sufficient, and 17-25% of the rats died within 48 hr following TNF administration. Every rat that received peritoneal polymorphonuclear leukocytes (PMNLs) died within 24 hr following the administration of TNF. On the other hand, administration of indomethacin to the rats in leukopenia prevented the toxic action of TNF completely, and all rats lived for 48 hr and showed no changes, compared to normal rats, in hematocrit, plasma transaminase, and body temperature. From these findings, the toxic action of TNF seems to result from increases in synthesis of prostaglandins (PGs) and activation of PMNLs. PMID- 2591032 TI - [Kala-azar in China from 1985 to 1988. Advisory Committee on Parasitic Diseases, MOPH]. AB - A total of 1,069 newly discovered cases of kala-azar (a few recurrent cases included) is recorded in China during the four year period from 1985 to 1988. The kala-azar patients were found in the Provinces and Autonomous Regions of Gansu, Sichuan, Xinjiang, Shaanxi, Shanxi, Inner-Mongolia and Shandong. Comparing with the 443 cases recorded during the previous 4 years period 1981-1984, significant uprise of the disease is evident, especially in the Provinces of Gansu and Sichuan. In southern Gansu and northern Sichuan, the incidence of visceral leishmaniasis in dogs is consistently high and these places are considered as areas endemic to leishmaniasis of canine source. Phlebotomus chinensis naturally infected with promastigotes are found in the mountainous regions 2,200 m and 1,500 m above the sea level respectively, and the promastigotes are identified as Leishmania donovani. As kala-azar patients and dogs infected with visceral leishmaniasis are mostly in the area below 1,600 m sea level and the area above 2,000 m sea level is unpopulated, the natural infection of sandflies was thought, therefore, to come from wild animal hosts and the natural nidus of kala-azar there warrants further investigation. It is suggested that consolidation and surveillance should be emphasized in endemic areas where leishmaniasis control has been very successful and research projects encouraged to meet the technical need for further achievement. PMID- 2591033 TI - [Predictive impact on malaria prevalence by hydraulic project of three gorges of the Yangtze River]. AB - Malaria had a wide distribution and high prevalence throughout the Three Gorges region of the Yangtze River. After antimalarial program, its incidence rate was reduced to 2.2% in 1985, but sporadic cases still occurred in 34.7% of the townships and local outbreaks were not uncommon. Therefore, potential factors of malaria outbreak are still present. It is predicted that maximum risk of malaria outbreak will take place, during construction and after the completion of the reservoir, the breeding sites of Anopheles would be extended to irrigation network, low-lying of flooded land, and malaria prevalence might be increased. PMID- 2591035 TI - [Use of double McAb sandwich ELISA to detect circulating antigen of Toxoplasma in infected rabbits]. AB - This paper reports on the cumulative positive frequencies of circulating antigen (CAg) detected in the sera of rabbits infected with Toxoplasma by using double McAb sandwich ELISA. The positive frequencies of rabbits with heavy and medium infection in the incubation period are 30.8% and 11.1%. Those with medium infection in acute, subacute and early chronic period are 86.1% and 76.7%, 43.3% and 32.0% with light infection. The positive rates of CAg in rabbits of medium and light infection rose progressively in acute period, but declined in subacute and early chronic period. Cross reaction with schistosomiasis and coccidiosis was all negative. This method of high specificity, sensitivity and duplication possesses certain value in the diagnosis of acute or active Toxoplasma infection and may be useful for the diagnosis in the early period. PMID- 2591034 TI - [Further studies on the mongolian jird model of Giardia lamblia]. AB - Seventy-seven Meriones unguiculatus were inoculated intra-esophageal with Giardia lamblia cysts isolated from the stool of a Giardia infected child. Correlation between oral dosage, course of infection, trophozoite distribution and the pathological changes in the small intestine of the infected jirds were studied. One (12.5%) of eight animals became infected with only 5 cysts. 10(4) cysts/jird or more was infective to nearly all the animals. Most of the infected animals (83%) excreted cysts and/or trophozoites intermittently. The extent of trophozoite colonization and their distribution in the small intestine varied with the time of infection, but not with the number of Giardia found in the feces. There was no direct correlation between the size of inoculum and the course of infection, the fecal output of cysts and/or trophozoites, or the intensity of pathological changes in the small intestine. The histopathological lesions induced by G. lamblia included cellular infiltration of the mucosa of the small bowel, nodular lymphoid hyperplasia, edema of the lamina propria and increase in mucous secretion. Necrobiosis and shedding of the epithelium was evident, and the mitotic figures of intestinal crypt increased significantly. The reduction of the villi to crypts ratio may indicate that the villi of small intestine were covered by relatively immature enterocytes, which may, partially, account for the malabsorption in giardiasis (Figs. 1-3). PMID- 2591036 TI - [Avidin-biotin-peroxidase complex enzyme-linked immunosorbent assay in the diagnosis of human multilocular echinococcosis]. AB - The Avidin-Biotin-Peroxidase Complex enzyme-linked immunosorbent assay (ABC ELISA) with antigen from gerbils infected with alveolar hydatid (GAH) was performed on the sera of 54 patients with multilocular echinococcosis, 107 patients with other diseases and 102 healthy adults. All the sera were diluted 1:200 and an S/N value greater than 2.2 was taken as positive. Both the sensitivity and specificity were 98.1%. The S/N value (mean +/- SD) of sera of the patients with multilocular echinococcosis, other parasitic diseases, tuberculosis, other diseases and healthy adults were: 5.9 +/- 3.0, 1.1 +/- 0.4, 1.4 +/- 0.8, 1.1 +/- 0.5 and 1.0 +/- 0.4. The geometric mean titre (GMT) of antibody measured by ABC-ELISA was 13.7 times that of ELISA. The quantity of serum used in ELISA was 8 times that of ABC-ELISA. ABC-ELISA might be particularly helpful to identify cases with low immune responsiveness. In the detection of alveolar hydatidosis and cystic disease with GAH antigens, the positivity was 98.1 and 67.1% with 87 and 25.6% having S/N greater than 5, respectively. It is suggested that in the diagnosis of hydatid diseases by ABC ELISA, homologous antigen should be used. The temperature and the incubation time needed for the present assay are practical, for the total time requires only 55 minutes. PMID- 2591037 TI - [Comparison in susceptibility of Anopheles dirus and Anopheles stephensi to B strain of Plasmodium cynomolgi]. AB - This paper reports on the comparative susceptibility of A. dirus (Hainan strain) and A. stephensi (Hor strain) to the B strain of P. cynomolgi in paired feeding experiments. In the most susceptible infective period, the infection rate in midgut and salivary gland of the two species was over 90%, the difference is not statistically significant. In relatively infective period, three experiments were performed, the infection rate in midgut of A. dirus was 24.4-60.4% with an average of 46.5% (53/114), and that of A. stephensi was 11.5-21.1% with an average of 14.2% (16/113). Statistically, experiment I showed no significant difference, the difference in experiment II was highly significant (P less than 0.01), and that in experiment III was significant (P less than 0.05). The number of oocysts in A. dirus was three times over that in A. stephensi. The infection rate of salivary gland in A. dirus was 18.2-55.0% with an average of 30.6% (19/62) and that of A. stephensi was 6.7-14.3% with an average of 9.5% (6/63). Statistically, only one of the three experiments showed significant difference (P less than 0.01). The result suggests that the susceptibility of A. dirus is higher than that of A. stephensi to the B strain of Plasmodium cynomolgi. PMID- 2591038 TI - [Ultrastructural studies on the spermatogenesis in diploid and triploid types of Paragonimus westermani]. AB - Diploid and triploid types of Paragonimus westermani were compared in the aspect of ultrastructure of spermatogenesis. The results showed that the process of spermatogenesis in the diploid type was normal. The cells at every stage are well developed. A great number of morphologically and functionally normal spermatozoa could be formed. On the other hand, the process of spermatogenesis in the triploid type was abnormal, the cells at every stage developed abnormally. They were apparently degenerated or vacuolated, lacking organelles. The cytophore was broken into small particles. No normal spermatozoa were found (Figs. 1-5). PMID- 2591039 TI - [Preliminary observation on feeding preference of Oncomelania for Sedum sarmentosum]. AB - As a result of screening, we discovered that Sedum sarmentosum Bunge was most preferred among 317 kinds of snail food. Both adult and young snails readily eat S. sarmentosum as evidenced by laboratory observation and dissection of the snails. In aquarium, more snails were attracted by S. sarmentosum than by Chinese cabbage and Chlorella suspension. On water surface, S. sarmentosum curtains attracted adult snails 2.1-3.7 times and immature snails 2.3-4.1 times more than rice straw curtains. PMID- 2591040 TI - [A comparison of the efficiency of density gradient and low-speed centrifugation methods for isolating Plasmodium sporozoites]. AB - P. yoelii sporozoites(Sp) in Anopheles stephensi were first isolated with low speed centrifugation and the Sp suspension was subsequently purified with the density gradient centrifugation. The recovery rates of Sp by the latter method is about 50 approximately 75% of that by the former, but few debris could be found in the Sp suspension and the infectivity of the Sp was not weakened as compared with the Sp obtained by low-speed method. Sp would retain partial infectivity, when its suspension was maintained in medium 199 at 4 degrees C for 48 hrs. When rats and mice were infected with these Sp, pathological changes of hepatocytes such as cloudy swelling or fatty degeneration, which had been evidenced to be induced by mosquito tissues, would be absent or present in the slightest degree. PMID- 2591041 TI - [Ultrastructural observation on the body wall of Pagumogonimus skrjabini]. AB - This paper deals with the ultrastructure of the body wall of adult Pagumogonimus skrjabini by transmission electron microscopy. Infected crabs were collected from Siyen, Hubei Province, and adult worms were obtained from the lungs of experimentally infected dogs 90 days post-infection. The normal structure of body wall of the P. skrjabini is composed of tegument, tegument cell, muscle muscle cell and protoplasmic tubules, all of which form together syncytium. The tegument contains external plasma membrane, tegument matrix and basal plasma membrane. The cell coat in fine granules is distributed over the whole external plasma membrane surface. The tegument matrix contains various secretory bodies, vesicles and mitochondria. The tegument cell is irregular in shape. Golgi complex, ribosome, autolysosome are seen in the cytoplasm. There are two layers of muscle, the external circular muscle and the inner longitudinal muscle layers. The nucleus of immature muscle cell has many heterochromatins, while the nucleus of mature muscle cell is large and round in shape. Mitochondria and glycogen granules are transmitted from muscle cell proper to the muscle by protoplasmic tubules (Figs. 1 approximately 7). PMID- 2591042 TI - Studies on methylmalonic acid in humans. I. Concentrations in serum and urinary excretion in normal subjects after feeding and during fasting, and after loading with protein, fat, sugar, isoleucine, and valine. AB - Determination of methylmalonic acid (MMA) in serum or urine for evaluation of tissue cobalamin (vitamin B12) deficiency is becoming an important diagnostic procedure. Here I present the first investigation of dietary influence on concentrations of MMA in serum and urine. Everyday meals caused an increase in urinary excretion, whereas the concentration in serum was not increased significantly. It is difficult to prime the accumulation of MMA in normal subjects by stressing the metabolic pathway; after loading subjects with 100 mmol of isoleucine or valine, the absolute amount of MMA excreted increased by only about 3 mumol. Its concentration in serum tended to decrease and its urinary excretion declined after lack of protein intake for more than 15 h. Although a linear relationship was demonstrated, for the first time, between concentrations in serum and urinary excretion, my results indicate that patients with early evidence of cobalamin deficiency and normal subjects may best be differentiated by measurements in serum, especially in the case of nonfasting (i.e., ambulatory) patients. PMID- 2591043 TI - Studies on methylmalonic acid in humans. II. Relationship between concentrations in serum and urinary excretion, and the correlation between serum cobalamin and accumulation of methylmalonic acid. AB - Methylmalonic acid (MMA) concentrations are increased in cobalamin (vitamin B12) deficiency, but the relative diagnostic usefulness of determination of MMA in serum vs urine has not yet been assessed. We obtained urine collections and matched serum samples from 28 healthy volunteers and from 20 consecutive patients admitted for clinical and hematological evaluation because of low cobalamin concentrations in serum. Increased concentrations of MMA in serum were found in 12 patients, in all of whom a clinical diagnosis of cobalamin deficiency was established. By contrast, cobalamin deficiency was excluded in seven of the eight remaining patients, who all had normal MMA concentrations. Here we report that linear relationships exist between MMA concentrations in serum (investigated range: 0.05-34.2 mumol/L) and MMA concentrations in urine (r = 0.74), concentrations relative to creatinine (r = 0.98), and MMA excretion rates (r = 0.97) (P less than 0.001 in each instance). Our data are consistent with glomerular filtration and passive reabsorption of MMA by the tubules. We demonstrate, for the first time, a negative correlation between concentrations of cobalamin and MMA in serum in clinical cobalamin deficiency (r = -0.69; P less than 0.01; n = 12); when the values for MMA were log transformed, the correlation with cobalamin was much better (r = -0.84; P less than 0.0005). PMID- 2591044 TI - Steroid profile for urine: reference values. AB - We describe a project, participated in by 24 institutions in The Netherlands and Belgium, to determine normal reference values for steroids in urine by capillary gas chromatography. Urine samples from 288 healthy volunteers were analyzed in triplicate. Reference values, expressed in mumol/24 h, were determined for androsterone, etiocholanolone, dehydroepiandrosterone, 11-keto-androsterone, 11 keto-etiocholanolone, 11-hydroxyandrosterone, 11-hydroxyetiocholanolone, pregnanediol, pregnanetriol, 11-desoxytetrahydrocortisol, tetrahydrocortisone, tetrahydrocortisol, allo-tetrahydrocortisol, and 17-keto- and 17-hydroxysteroids. We also determined reference ratios for etiocholanolone/androsterone, tetrahydrocortisone/tetrahydrocortisol, and tetrahydrocortisol/allo tetrahydrocortisol; an upper limit of a discriminant function to establish polycystic ovarian disease; and reference values for 24-h urine volume and creatinine excretion. Reference values were determined separately for men and women, each in six age categories: 0-3 months, 4 months-12 years, 13-16 years, 17 50 years, 51-70 years, and older than 70 years. We conclude that these reference values are reliable and form a basis for quantitative interpretation of steroid profiles. PMID- 2591045 TI - Simultaneous liquid-chromatographic determination of vitamin K1 and vitamin E in serum. AB - We describe a high-performance liquid chromatographic procedure for the simultaneous measurement of vitamins K1 and E in human serum. Delipidated human serum (free of vitamins K1 and E) was used to make standard solutions of these vitamins, and cetyl naphthoate and alpha-tocopheryl acetate were the internal standards for vitamin K1 and vitamin E, respectively. A simple, novel separation method utilizing liquid-liquid partition chromatography was used as a preparative "clean-up" procedure. Cetyl naphthoate and vitamin K1 (after post-column reduction) were detected by fluorescence, alpha-tocopheryl acetate and vitamin E by ultraviolet absorption. Sensitivity (detection limit) of the assay was 30 pg for vitamin K1 and 5 ng for vitamin E per injection. The method is specific, precise, and more rapid than previously described procedures. Within- and between assay CVs were 8.1% and 12.9%, respectively, for vitamin K1; 3.5% and 6.0%, respectively, for vitamin E. Analytical recoveries of vitamins K1 and E were 80% and 93%, respectively, from serum and from delipidated serum (standards). The average neonatal serum concentration of vitamin K1 was 83 ng/L, 2.5 mg/L for vitamin E; for normolipidemic adults, the values were 343 ng/L and 7.9 mg/L, respectively, and for hyperlipidemic adults, 541 ng/L and 11.1 mg/L, respectively. PMID- 2591046 TI - Urinary neopterin concentrations vs total neopterins for clinical utility. AB - Neopterin measurements are especially useful as an early marker in (e.g.) allograft rejections and in patients infected with human immunodeficiency virus type 1 (HIV-1). An increased concentration of total neopterins (neopterin + dihydroneopterin) is also a significant marker in patients with HIV-1 infection. In this study we compared concentrations of neopterin and total neopterins in urine samples from 77 homosexual men with and 73 without established HIV-1 infection. HIV-1-seropositive homosexual men had higher concentrations of neopterin and total neopterins (and 7,8-dihydroneopterin) in their urine than did those who were HIV-1-seronegative, and there was a close correlation between neopterin and total neopterins. Both neopterin variables correlated inversely with CD4+ T-cell counts and CD4+/CD8+ T-cell ratios but not with CD8+ T-cell counts in the HIV-1-seropositive men. Our data indicate that measurements of neopterin and total neopterins are of almost equal potential for clinical diagnosis. However, when measuring total neopterins, which includes oxidation of 7,8-dihydroneopterin to neopterin, more strict requirements of sample collection and handling are necessary to avoid degradation of the 7,8-dihydro derivative. PMID- 2591047 TI - Time-resolved fluoroimmunoassay of aflatoxins. AB - Preparation of purified and Eu-labeled antibodies specific for aflatoxins is described. Their use is illustrated by a solid-phase competitive time-resolved fluoroimmunoassay, results of which were correlated with those of an enzyme linked immunosorbent assay based on use of the unmodified antibody to aflatoxin. This procedure is discussed as a quick, sensitive, and reliable immunoassay for use in mycotoxin screening in foodstuffs and body fluids. PMID- 2591048 TI - A sensitive method of screening for urinary porphobilinogen. AB - In this screening method for urinary porphobilinogen (PBG), urine is added to Dowex 2 resin under alkaline conditions in a test tube and mixed. The supernate is removed and the adsorbed PBG is eluted with acid and reacted with Ehrlich's reagent. We compared results with those by the Watson-Schwartz screening method, using urine samples from normal people with and without added PBG. At a PBG concentration of about five times the upper limit of normal, the resin method gave a sensitivity of 100%; the Watson-Schwartz method gave a sensitivity of 51%. At lower PBG concentrations of just over and twice the upper limit of normal, the sensitivity by the resin method was respectively 97% and 100%. With normal urine samples, the resin method gave negative results for all samples (100% specificity) and the Watson-Schwartz had 95% specificity. Our data indicate that the resin method is sensitive, specific, and reliable and is superior to the Watson-Schwartz method. PMID- 2591049 TI - Effect of transport conditions on the stability of biochemical markers in blood. AB - We examined the stability of lipids, carotenoids, alpha-tocopherol, and endogenous hormones in plasma prepared from whole blood that had been mailed to a central location for processing. Initially, to simulate transport conditions, whole-blood samples were stored in the laboratory, either at room temperature or cooled, for up to 72 h before processing. In the latter samples, lipid concentrations changed up to 1.4% per day, carotenoids up to -5.5%, and hormones up to 9.5%. In a second study, analyte concentrations in plasma from cooled whole blood mailed via overnight courier were compared with those from plasma that had been immediately separated, frozen, and mailed via overnight courier. Concentrations of cholesterol, high-density lipoprotein subfraction 3, apolipoprotein B, and retinol were stable. Overall, for each marker except estradiol, the between-person variation was at least twice the within-person variation. In a third study, at least 340 micrograms of DNA was recovered from 30 mL of cool-shipped whole blood. Our results indicate that shipping whole-blood samples by overnight courier is feasible for assay of several biochemical markers of interest in epidemiological research. PMID- 2591050 TI - Influence of O.C.T. embedding compound on determinations of estrogen and progestin receptors in breast cancer. AB - Estrogen receptor (ER) and progestin receptor (PR) concentrations in tumor biopsies are important predictive indicators of a clinical response to endocrine therapy of breast cancer. To assess interference of O.C.T. (optimum cutting temperature) embedding compound in assays of ER and PR by radioligand binding, we determined specific binding capacities and affinities of ER and PR in cytosols by a multipoint titration method, using split samples of 14 breast-tumor biopsies, one portion serving as untreated control, the other treated with O.C.T. There was no statistically significant difference between these two groups. We then compared these data with those of historical controls analyzed both in the presence and absence of sodium molybdate (10 mmol/L). Eighty breast-tumor specimens (mean +/- SD patients' ages, 59 +/- 14 y) embedded in O.C.T. compound and analyzed without molybdate gave ER and PR values that differed insignificantly from those for 306 samples (patients' ages, 61 +/- 14 y) untreated with O.C.T. Thirty-nine specimens (patients' ages, 58 +/- 15 y) embedded in O.C.T. compound were analyzed in the presence of molybdate and compared with the results for 288 specimens (patients' ages, 61 +/- 14 y) untreated with O.C.T. Again, there was an insignificant difference in the concentrations and affinities of receptors in the two groups. Evidently O.C.T. compound does not alter the receptor status of tumor biopsies. PMID- 2591051 TI - Lactate dehydrogenase isoenzyme composition of human platelets. AB - The LDH isoenzyme composition of 12 platelet preparations was determined by electrophoresis. The mean (+/- SD) percentages of LDH-1, LDH-2, LDH-3, LDH-4, and LDH-5 were 16.6 +/- 1.7, 30.1 +/- 1.0, 34.2 +/- 1.3, 18.2 +/- 1.3, and 0.9 +/- 1.1, respectively. In comparison with previous data, these data show identical ranking of the prevalence of each isoenzyme but significantly different percentages, particularly of LDH-1 and LDH-4. The release of platelet LDH by freezing and thawing differed little from that by homogenization. PMID- 2591052 TI - Assessment of renal function by serum creatinine and creatinine clearance: glomerular filtration rate estimated by four procedures. AB - We compared creatinine concentrations in serum and urine and creatinine clearances determined by two Jaffe (Beckman's "Astra," Boehringer Mannheim Diagnostics) and two enzymatic (Kodak, Boehringer Mannheim Diagnostics) methods. Serum creatinine and creatinine clearances determined by each method were also compared with the glomerular filtration rate as measured with use of sodium [125I]iothalamate in patients with a wide range of renal function. Results between methods correlated excellently, but we saw clear method-dependent biases of up to 2.9 mg/L for serum. The highest serum creatinine values and the lowest creatinine clearances were obtained with Boehringer Mannheim Diagnostics' Jaffe method. The reciprocal of the serum creatinine and the creatinine clearance also correlated well with the glomerular filtration rate, but all methods over estimated the glomerular filtration rates to varying degrees. Appropriate standardization of methods appears to be as important as method principle for establishing an accurate relationship between creatinine determinations and glomerular filtration rate. PMID- 2591053 TI - Rapid enzymatic determination of urinary oxalate. AB - This new reagent kit for the quantitative measurement of oxalate in urine is a modification of an earlier Sigma oxalate assay procedure (procedure no. 590), a coupled enzyme assay involving oxalate oxidase and horseradish peroxidase. The new analytical procedure includes methods for processing urine specimens to eliminate interference with oxalate color development at 590 nm by ascorbic acid, divalent cations, and other urinary constituents. The reaction is complete in less than 5 min, and results are linearly related to oxalate concentration up to at least 1 mmol/L. Assay sensitivity and within-run and between-run precision were within the limits acceptable for other urinary oxalate procedures. Analytical recovery of added oxalate was close to 100%. This specific, simple, rapid procedure is suitable for routine clinical use. PMID- 2591054 TI - Assessment of a trial screening program for congenital adrenal hyperplasia in Portugal based on an antibody-coated tube RIA for 17 alpha-OH-progesterone. PMID- 2591055 TI - Acute changes in serum thyrotrophin in treated Addison's disease. AB - Serum and salivary cortisol, plasma ACTH and serum TSH, free T4, free T3, PRL, LH and FSH were measured before and hourly after the morning steroid replacement therapy of five patients with Addison's disease. In the 4 h after hydrocortisone the levels of TSH fell in all five patients, the levels (mIU/l) decreasing from 6.8 to 3.8; 0.9 to 0.6; 24.3 to 13.2; 28.1 to 7.4 and 17.2 to 11.6. No such change was seen when the procedure was repeated with the morning steroid dose withheld. In two patients, dexamethasone produced similar changes in serum TSH to those observed with hydrocortisone. Steroid therapy had no consistent effect on LH, FSH and PRL levels. Our results show that the time interval between taking medication and withdrawing blood samples should be considered when interpreting TSH levels in treated Addison's disease. PMID- 2591056 TI - Bone mass in hirsute women with androgen excess. AB - The spinal and femoral bone mass of 32 hirsute women with oligomenorrhoea and androgen excess was measured using dual photon absorptiometry and compared with the bone mass of 32 control women with regular menstrual cycles. Despite significantly lower oestradiol levels in the hirsute population there was no significant difference in the bone mass. Furthermore there was no significant difference in bone mass in five hirsute women with undetectable levels of oestradiol. It is concluded that androgen excess can maintain normal bone mass in the face of low or undetectable oestradiol levels. PMID- 2591057 TI - Dihydrotestosterone regulates plasma sex-hormone-binding globulin in prepubertal males. AB - Plasma levels of sex-hormone-binding globulin (SHBG) in man are known to be regulated up and down by oestradiol and testosterone, respectively. To determine whether testosterone reduces SHBG level directly or via its conversion into dihydrotestosterone before puberty, the changes of plasma SHBG, testosterone, oestradiol and dihydrotestosterone following human chorionic gonadotrophin stimulation are studied in ten 5 alpha-reductase-deficient and in six normal prepubertal boys. Three main observations provide evidence that dihydrotestosterone plays a major role in SHBG regulation. (1) Basal plasma SHBG in 5 alpha-reductase-deficient is higher than in normal boys (P less than 0.1). (2) Circulating SHBG fails to decrease (P greater than 0.1) after human chorionic gonadotrophin stimulation despite striking elevation of plasma testosterone in 5 alpha-reductase deficiency where negligible dihydrotestosterone response occurs. This is in contrast to normal boys where SHBG is significantly reduced (P less than 0.01) after stimulation. (3). In normal boys the magnitude of plasma dihydrotestosterone response to human chorionic gonadotrophin correlates with that of SHBG (r = 0.72) more than testosterone does versus SHBG (r = 0.36). It is concluded that dihydrotestosterone decreases SHBG concentration in plasma of prepubertal boys. At least part of the observed decrease in SHBG following testosterone administration in earlier reports must have occurred after its conversion to dihydrotestosterone. PMID- 2591058 TI - Renal function and electrolyte levels in hyperthyroidism: urinary protein excretion and the plasma concentrations of urea, creatinine, uric acid, hydrogen ion and electrolytes. AB - In order to help clarify the effects of hyperthyroidism on renal function and electrolyte metabolism, we measured the venous plasma concentrations of urea, creatinine, urate, hydrogen ion and electrolytes, and the urinary concentrations of total protein, albumin, retinol-binding protein, N-acetyl-beta-D glucosaminidase activity, and creatinine in patients when hyperthyroid and again after they had been euthyroid for at least 4 months. Significant (P less than 0.05) decreases in the mean plasma concentrations of urate and chloride and significant increases in creatinine, total CO2 and hydrogen ion mean concentrations were observed when the patients became euthyroid. The mean concentrations of sodium, potassium and urea did not change significantly. The values of the ratios total protein/creatinine, albumin/creatinine, N acetylglucosaminidase/creatinine and retinol-binding protein/creatinine were all significantly (P less than 0.05) elevated in random urine specimens obtained from hyperthyroid patients as compared to the values when euthyroid. Mild proteinuria occurs in most thyrotoxic patients which does not appear to be due predominantly to either glomerular or tubular renal injury. The changes in plasma analytes that were observed may be attributed to increases in glomerular filtration rate and tissue nucleic acid turnover and a tendency to respiratory alkalosis in the hyperthyroid patients. PMID- 2591059 TI - Sella size and contents in Sheehan's syndrome. AB - High-resolution computerized tomography was used to assess the size and contents of the pituitary fossa in 57 patients with Sheehan's syndrome and 17 female control subjects. No correlation was found either in the patients or the control group, between sella volume and age, weight, height, parity or time interval from postpartum haemorrhage to scan. The sella volume showed wide variation. The mean sella volume for all patients was 565 mm3 (SD 292) in contrast to a mean volume for the controls of 922 mm3 (SD 155). The difference was statistically significant (P less than 0.001) using the Mann-Whitney test. The stalk was visualized in 46 patients (81%) (20 of these showed other pituitary tissue in addition). The remaining 11 patients showed no pituitary tissue, and only pure CSF density was observed. PMID- 2591060 TI - The cardiovascular effects of octreotide treatment in acromegaly: an echocardiographic study. AB - Nine acromegalic patients were treated by the somatostatin analogue SMS 201-995 octreotide (Sandostatin (octreotide), Sandoz, Basle, Switzerland] 250 micrograms/day in 4 divided s.c. injections (50 + 50 + 50 + 100 micrograms) for 1 month, 250 micrograms/24 has continuous s.c. infusions for another month and thereafter 200 micrograms three times daily as s.c. injections. Echocardiography was performed before the treatment, following 1 month of octreotide s.c. infusion/injection and after 6 and 12 months of octreotide treatment. No differences in serum growth hormone, heart rate, blood pressure, cardiac contractility or left ventricular wall mass or wall thickness were found between the infusion and the injection periods. As compared to the pretreatment levels serum growth hormone decreased by 62 and 66% respectively following 6 and 12 months octreotide treatment. The heart rate per minute (+/- SD) decreased from the pretreatment level of 75 +/- 12 to 63 +/- 13 (P less than 0.007) at month 12. The systolic and the diastolic blood pressure decreased from the pretreatment level of 121 +/- 8 and 79 +/- 5 mmHg respectively to 108 +/- 7 (P less than 0.0007) and 71 +/- 7 mmHg (P less than 0.0001) respectively at month 12.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591061 TI - Low serum TSH with normal total thyroid hormone levels: an indicator of free T4 excess. AB - We have studied 18 patients with low serum thyrotrophin (TSH) levels accompanied by normal thyroxine (T4) and triiodothyronine (T3) levels in order to clarify whether or not they are thyrotoxic. Serum T4, T3, free T3, free T4 and TSH were estimated three times weekly for 3-4 weeks. Thyroxine binding globulin (TBG) levels were estimated on one occasion only. Thyroid hormone data were expressed as the cumulative probability of having at least one result above the relevant normal range by the nth sample (Pn). For free T4 this probability was 61% by the 10th sample. Free T4 values were confined to the upper half of the normal range or above throughout the study. In contrast, free T3 values were distributed evenly within the normal range (P10 = 12%). For total T4 and total T3, P10 was 34 and 11% respectively. Thus, subjects with subnormal TSH levels but normal T4 and T3 levels have been shown to have elevated serum free T4 levels, an indicator of biochemical hyperthyroidism. PMID- 2591062 TI - Changes in blood pressure and plasma noradrenaline in short-term hypothyroidism. AB - Thirteen patients who had undergone thyroidectomy for thyroid cancer stopped thyroid hormone replacement prior to follow-up radioactive iodine scans. Thyroxine was replaced by triiodothyronine (T3) for 4 weeks and T3 was stopped 2 weeks before the scan and 16 to 19 days before blood pressure measurement and venipuncture for obtaining plasma noradrenaline samples. During this time, a small but significant decrease in systolic blood pressure occurred, both supine and standing, while the corresponding plasma noradrenaline levels increased significantly. These findings indicate that the acute cardiovascular effect of brief thyroid hormone withdrawal is a decrease in blood pressure rather than the increase often observed in chronic hypothyroidism, and that plasma noradrenaline levels may increase much sooner than previously reported after onset of hypothyroidism. PMID- 2591063 TI - Failure of long-term cyproheptadine therapy in lowering growth hormone levels in acromegaly. AB - Basal and post-glucose growth hormone (GH) responses were evaluated in 10 acromegalics receiving cyproheptadine (cypro) 4 mg 6 hourly at 2 and 21 days after initiating therapy. Of the 10 patients, six had macroadenomas with varying degree of suprasellar extensions, one a microadenoma and three had persistent hypersomatotropism despite pituitary adenomectomy due to residual tumour. The basal and post-glucose GH showed no significant change in all, except one with a pituitary microadenoma. His GH was reduced from 680 to 108 mU/L on the second and 82 mU/l on the 21st day of cypro therapy. These data do not suggest any therapeutic role of cypro in the management of acromegaly. PMID- 2591064 TI - Effects of Lugol's solution on thyroid function in normals and patients with untreated thyrotoxicosis. AB - Thirty-eight normal volunteers and 10 patients with untreated thyrotoxicosis were each given 0.5 ml of Lugol's solution daily for 10 days. On days 0, 5, 10, 15 and 20, serum levels of T4, free T4, T3 and TSH (by sensitive immunoradiometric assay) were measured. In normal subjects, the serum concentrations of free T4 declined significantly at day 10 while TSH levels were significantly increased at days 5, 10 and 15. Serum levels of T4 and T3 did not change significantly. All the observed changes took place within the limits of normal ranges for the hormones mentioned. In contrast, in the thyrotoxic subjects, both T4 and T3 were significantly decreased at days 5 and 10, while serum TSH remained below detection limit (0.14 mU/l) throughout the study. Short exposure to excessive iodide in normal subjects affects T4 and T3 release and this effect could be partially overcome by compensatory increase in TSH. In thyrotoxicosis, lack of compensatory increase in TSH results in rapid decreases in T4 and T3 levels. The integrity of the hypothalamo-pituitary-thyroidal axis may be effectively assessed by measuring TSH response to iodide suppression, using a highly sensitive immunoradiometric assay. PMID- 2591065 TI - Quantification of urinary growth hormone (GH) excretion by centrifugal ultrafiltration and radioimmunoassay: appraisal of the relationship between 24 h urinary GH and mean 24 h serum GH levels in normal and abnormal states of GH secretion. AB - We have applied a simple method for the quantification of 24 h urinary GH excretion (24 h UGH), combining centrifugal ultrafiltration and radio-immunoassay (RIA), to an appraisal of the relationship between 24 h UGH and mean 24 h serum GH levels in normal and abnormal states of GH secretion. Forty-four subjects, comprising 13 normal adults, 12 short-statured subjects and 19 subjects with active acromegaly, underwent blood sampling at 20-min intervals and concurrent urine collection for 24 h. Mean 24 h serum GH and 24 h UGH were also determined in four post-menopausal women before and during cyclical oestrogen replacement therapy, and 24 h UGH was measured in six normal men prior to and following the subcutaneous administration of biosynthetic GH (0.2 IU/kg). Each subject's mean 24 h serum GH level was determined by assaying a 'pooled' sample, derived from equal aliquots of the 73 serum samples obtained during the 24 h study. The method for quantification of 24 h UGH employs centrifugal microconcentrators, and involves a 50-fold concentration of urine, followed by dialysis and RIA. Surface adsorptive hormone loss during sample collection and ultrafiltration is minimized by the prior addition of bovine serum albumin to the urine collection container. Immunoreactive GH in ultrafiltered urine dilutes in parallel with the RIA standard curve. GH is stable in urine stored at - 20 degrees C for at least 12 months. There was a highly significant correlation between 24 h UGH and mean 24 h serum GH values obtained from the combined population of normal adults (including the post-menopausal women during oestrogen therapy) and short-statured subjects (r = 0.69, P less than 0.0001). A significant correlation was also found in short statured subjects alone (r = 0.63, P less than 0.05). In contrast, there was no significant correlation between 24 h UGH and mean 24 h serum GH in subjects with active acromegaly, and their 24 h UGH values were not distinguishable from those of the 'non-acromegalic' subjects. A significant increase in 24 h UGH occurred in the post-menopausal women given cyclical oestrogen replacement therapy (9.7 +/- 2.6 (mean +/- SE) to 24.6 +/- 1.0 muIU/mmol creatinine, P less than 0.02), reflecting the increase in their mean 24 h serum GH levels (0.8 +/- 0.3 to 5.3 +/ 0.7 mIU/l, P less than 0.01). Twenty-four hour UGH increased from 4.6 +/- 0.6 to 17.1 +/- 2.1 muIU/mmol creatinine (P less than 0.002) in the men given biosynthetic GH. Twenty-four hour UGH measurements reflect mean 24 h serum GH levels in normal adults and short-statured subjects. While the measurement of 24 h UGH shows promise as an investigative tool, our results cast doubt on its use in the diagnosis of acromegaly. PMID- 2591066 TI - Evidence for a major additive gene in ulcerative colitis. AB - Complex segregation analysis of 124 families with ulcerative colitis with two or more affected individuals suggests a rare additive major gene causing the disease with about 20% affected among the heterozygotes for the gene. There was no evidence for multifactorial inheritance. PMID- 2591068 TI - Autosomal dominant transmission of isolated congenital vertical talus. AB - We report vertical transmission of isolated congenital vertical talus through three generations of a Honduran family. Five of nine affected family members were examined and the diagnosis was confirmed radiographically. There was incomplete penetrance in one clinically unaffected woman with two affected children. Bilateral and unilateral involvement was seen with a wide range of severity. Based on this family and on cases reviewed from the literature, we propose that isolated congenital vertical talus can be inherited as an autosomal dominant trait with variable expression and incomplete penetrance. PMID- 2591067 TI - Linkage between alpha 1B-glycoprotein (A1BG) and Lutheran (LU) red blood group system: assignment to chromosome 19: new genetic variants of A1BG. AB - alpha 1B-glycoprotein (A1BG) polymorphism was examined in a Danish family material (no. 604-1505) with particular regard to markers on chromosome 19. For A1BG-LU we found a lod score z = 3.06 at theta = 0.05 in males, and z = 1.42 at theta = 0.10 in females, which assigns A1BG to chromosome 19. Close linkage to C3, SE, PEPD, APOC2, D19S7, D19S8 and D19S9 was excluded. The most likely order would appear to be C3-SE-LU-A1BG. PMID- 2591069 TI - Hereditary spastic diplegia with mental retardation in two young siblings. AB - Two young siblings with hereditary spastic diplegia and mental retardation (Book's syndrome) have had detailed clinical investigations since infancy. The inheritance pattern of this syndrome in the present family fits well with an autosomal recessive trait--with affected sibs of opposite sex, born to consanguineous healthy parents. PMID- 2591070 TI - A complex deformity of appendicular skeleton and shoulder with congenital heart disease in three generations of a Jordanian family. AB - A sibship is reported of three generations of a Jordanian family of normal intelligence with a complex malformation of upper extremity, shoulder and thorax, which is combined with variously expressed congenital heart disease. The deformity consists of a flat glenoid fossa, a hypoplastic scapula, aplasia of the humerus and/or radius, bony spurs of the elbow joint and in the shoulder region, hypoplasia of the carpal joints and hypodactyly with aplasia of the thumb. The claviculae are short, thick and abnormally curved and there are kyphoscoliosis and pectus excavatum. Four siblings show congenital heart disease. Pelvis and lower extremity are normal. The condition is inherited as a Mendelian autosomal dominant. PMID- 2591071 TI - An apparently new autosomal recessive syndrome with facial dysmorphism, macrocephaly, myopia and Dandy-Walker malformation. AB - In this report we describe an apparently new MCA-MR syndrome with Dandy-Walker malformation in three severely mentally retarded siblings born to normal, non consanguineous parents. In addition, they presented macrocephaly, facial dysmorphism, extreme myopia and brachytelephalangy with short and broad finger nails. PMID- 2591072 TI - Achalasia microcephaly syndrome in a patient with consanguineous parents: support for a.m. being a distinct autosomal recessive condition. AB - A 4 9/12-year-old boy with achalasia microcephaly syndrome (AMS), born to a consanguineous couple, is reported. Comparative analysis of this case and the patients previously described in a Mexican family supports the notion that the syndrome is a distinct autosomal recessive condition. It is interesting that the area of origin and ethnicity of both the present and the previously reported cases is northwest Mexico. PMID- 2591073 TI - High incidence of Bardet Biedl syndrome among the Bedouin. PMID- 2591074 TI - Phenotypical features of an unique Irish family with severe autosomal recessive Osteogenesis imperfecta. PMID- 2591075 TI - 3C syndrome: another case. PMID- 2591076 TI - Large cell lymphocytoma--a clinicopathological study. AB - Fourteen patients with large cell lymphocytoma were studied. They presented with solitary or small numbers of grouped nodules on the trunk or head and neck region, which histologically consisted of diffuse and nodular dermal aggregates of lymphoid cells. A proportion of these cells were large with clear cytoplasm and a varying degree of nuclear atypia. An infiltrate of small mature lymphocytes surrounded and extended between the zones of larger cells. Mitotic figures and pleomorphic cells were frequent and, on the basis of this histopathology, an initial diagnosis of cutaneous lymphoma had frequently been made. There were eight male and six female patients with a mean age at presentation of 40 years (range 14-71) who were followed up for a period of between 4 and 31 years (mean = 14.6). Thirteen of the 14 are alive and well, and there has been no evidence of systemic involvement in any of the patients; one patient died of chronic renal failure and pneumonia. Monoclonal antibody studies on paraffin sections showed the presence of lymphoid cells of B and T cell lineage in large cell lymphocytoma. We believe that these patients have a variety of cutaneous lymphocytic infiltrate, large cell lymphocytoma, which has characteristic clinical and histological features and is important to recognize because of its benign course. Large cell lymphocytoma has been used to describe a nodular lymphoid infiltrate of the skin composed principally of large follicular centre cells. Often these lesions had been diagnosed as reticulum cell sarcoma but, on follow-up, all the patients were alive and well.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591077 TI - Stimulated eccrine gland function in primary Sjogren's syndrome. AB - Sweat secretion rate, stimulated by iontophoresis of pilocarpine, was measured in 22 patients with primary Sjogren's syndrome and 22 age- and sex-matched normal control subjects. There was no significant difference in measured sweat rates (P = 0.45). We conclude that the complaint of dryness of the skin in patients with Sjogren's syndrome is not due to decreased eccrine gland secretion. PMID- 2591078 TI - The duration of Grenz ray-induced suppression of allergic contact dermatitis and its correlation with the density of Langerhans cells in human epidermis. AB - Recent investigations have shown that Grenz rays can suppress the allergic contact dermatitis reaction completely and that Langerhans cells, identified by OKT6 antibodies and electron microscopy, disappear from the epidermis at the same time. It is not known for how long this suppression lasts. This has been investigated in 28 nickel-sensitive patients who were given Grenz rays (3 Gy) on the back, once a week for 3 weeks. The patients were then divided into four groups and tested with patch tests for nickel at 1, 7, 14 and 21 days after the last Grenz ray treatment. Biopsies were taken from positive patch test sites, and from the corresponding opposite control. They were labelled with OKT6 antibodies to detect Langerhans cells. The patch test reactions were suppressed and the Langerhans cell density was decreased initially. These changes were restored after 3 and 6 weeks, respectively. The results show that the effect of Grenz rays on eczematous reactions extends to a maximum of 3 weeks and imply that Langerhans cells are necessary for the elicitation of the efferent phase of allergic contact dermatitis. PMID- 2591079 TI - Time-course of corticosteroid-induced blood flow reduction in normal cutaneous tissue--quantitative measurements during 72 h of treatment. AB - In eight healthy individuals, the skin fold between the thumb and the forefinger was treated with 0.05% clobetasol propionate ointment under a hydrocolloid occlusive dressing. Using the atraumatic epicutaneous 133Xe wash-out technique on the outer 2 mm of the skin fold, covering the rest of the hand with a lead shield, we were able to monitor cutaneous blood flow. Blood flow was measured after 0, 10, 24, 48 and 72 h of treatment. During the first 10 h of treatment no significant change in blood flow was observed. However, compared to untreated tissue, cutaneous blood flow decreased significantly after a 24-h period (P less than 0.05). Furthermore a significant blood flow reduction from 0-48 (P less than 0.02) and from 0-72 h (P less than 0.01) was observed. Placebo did not decrease cutaneous blood flow, but a minor increase was demonstrated. The results of the present work demonstrate a long-lasting blood flow reducing effect of topical corticosteroid in normal human cutaneous tissue. PMID- 2591080 TI - Langerhans cells in delayed skin reactions to inhalant allergens in atopic dermatitis--an electron microscopic study. AB - Langerhans cells at the site of patch tests to inhaled allergens in patients with atopic dermatitis were investigated. Within 24 h the Langerhans cells showed increased cellular activity and became apposed to mononuclear cells. This supports the view that Langerhans cells are involved in antigen presentation in atopic dermatitis. PMID- 2591081 TI - Kaposi's sarcoma in a homosexual--10 years on. AB - Kaposi's sarcoma is seen in one of several clinical settings. Before the recognition of the acquired immune deficiency syndrome (AIDS) in the early 1980s, the most frequent presentation of Kaposi's sarcoma in the UK was the so-called 'classical' form of the disease. The most common form of Kaposi's sarcoma in this country is now that associated with AIDS, which particularly affects young male homosexuals. Here we describe a homosexual man who has developed many Kaposi's sarcoma tumours during the past 10 years. The disease has run a benign course and there is no evidence of infection with human immunodeficiency virus (HIV). PMID- 2591082 TI - Cock's peculiar tumour. AB - We describe the typical clinical and histological features of a case of giant proliferative pilar cyst which was complicated by severe iron deficiency anaemia. The condition, described by Cock in 1852 and eponymously known as Cock's peculiar tumour, is compared to giant proliferative pilar cyst. These entities are probably synonymous. PMID- 2591083 TI - Resolution of atopic dermatitis in a patient treated with cyclosporin. AB - There are theoretical reasons to anticipate a beneficial action of cyclosporin in atopic dermatitis. We describe a patient with severe atopic dermatitis who responded dramatically while receiving cyclosporin for the treatment of lymphoma. Cyclosporin may have a useful role in patients with resistant atopic dermatitis. PMID- 2591084 TI - Atrophic alopecia in the Hallermann-Strieff syndrome. AB - We report a case of the Hallermann-Strieff syndrome with focal scalp atrophy and associated patchy hair loss. Cases of the Hallermann-Strieff syndrome (a branchial arch syndrome) often present with ocular abnormalities in infancy but they also show a number of other abnormalities including a characteristic facial appearance, proportionate dwarfism, cutaneous atrophy, hypotrichosis and dental anomalies. PMID- 2591085 TI - Occurrence of pemphigus vulgaris antigen in shedding snake epidermis. PMID- 2591086 TI - Psoriasis induced by topically applied indomethacin. PMID- 2591087 TI - Etretinate and severe nail plate dystrophies. PMID- 2591088 TI - Lupus erythematosus diagnosis. PMID- 2591089 TI - A simple method for the study of scale pattern and effects of a moisturizer- qualitative and quantitative evaluation by D-Squame tape compared with parameters of epidermal hydration. AB - A new tape (D-Squame tape) made for scale pattern assessments was used to study epidermal effects of an oil-in-water emulsion applied at random to forearm skin of 16 volunteers. The contralateral forearm served as an untreated control. The emulsion was applied twice daily for 7 days. Tapes were assessed visually in a medical viewer, and a special system for measurement of optical transmission of the tapes was established. Visual evaluation showed (Day 7) an altered pattern in nine volunteers with an absence of flakes on the treated side, which was not seen on the control side. The optical transmission of the tapes from the 16 volunteers was significantly increased in samples from the test side (P less than 0.001). One week after cessation of treatment the transmission was still increased (P less than 0.02), and one volunteer presented an altered scale pattern according to visual grading. Measurements of electrical conductance and capacitance, both parameters of epidermal hydration, gave similar results, i.e., increased values on Day 7 and increased conductance 1 week later. Thus, the epidermal effects of the emulsion were protracted. Evaluation of the tape method showed this to be reproducible and valid. The method is easy to use and suited for qualitative and quantitative evaluation of variations in the scale pattern of human skin. PMID- 2591090 TI - Antipsoriatic effect of semi-occlusive treatment--O2-consumption, blood flow and temperature measurements compared to clinical parameters. AB - Ten patients with plaque-type psoriasis were treated by applying semi-permeable hydrocolloid dressings (Com-feel, Coloplast, Denmark) and the effect compared to untreated skin. The treatment effect was evaluated by: (a) O2-consumption as measured by a TCM-2 oxygen-monitor; (b) blood flow as measured by laser-Doppler flowmetry; (c) temperature measurements using thermocouples; (d) a clinical score. The treatment effect was evaluated after 1, 2 and 7 days and although there was a significant and sustained improvement in the clinical score following Day 7 (P less than 0.05), this was not associated with a significant change in any of the objective measurements during the study (P greater than 0.05). In the same patients the clinical effect of occlusion was evaluated after 21 days in another area. A pronounced effect was observed comparable to, equal to, or better than that of crude coal tar given as daily applications followed by bathing. There was no significant change in any of the parameters at the sites of untreated psoriasis. PMID- 2591091 TI - Hand venous hypertension complicating arterio-venous fistula construction for haemodialysis. AB - Vascular complications of arterio-venous fistula construction for haemodialysis are rare. We report a patient who developed the hand venous hypertension syndrome with ulceration, 2 years after successful construction of a side-to-side radio cephalic fistula at the wrist. The surgical treatment was ligation of the distended vein immediately distal to the fistula in the hand, and fistula function was preserved. The ulceration healed within 2 weeks of surgery. This complication had not been seen previously in the Dialysis Unit at Cardiff Royal Infirmary where, over the past 20 years, 800 fistulae have been constructed. PMID- 2591092 TI - Short-term methotrexate administration by low-dose infusion--does it influence clearance of psoriasis? AB - Twenty-four patients between them received 86 low-dose methotrexate infusions (given over 36 or 48 h) delivered by a Graseby syringe pump in addition to conventional topical therapy during hospital admission for treatment of severe psoriasis (either erythrodermic or severe widespread plaque-type). The average length of hospital stay, usually the time taken to achieve complete clearance, and the average relapse time in the group of patients overall showed no differences from a control group of 25 patients (matched for age and sex) having a similar severity of psoriasis treated without methotrexate. However, separation of the patients into three sub-groups (erythrodermic, severe and 'unstable' widespread plaque-type, and severe and 'stable' widespread plaque-type disease) revealed that erythrodermic patients, as expected, cleared significantly quicker when receiving methotrexate although severe and 'unstable' widespread plaque-type patients had their clearance times possibly prolonged by short-term methotrexate administration. Although methotrexate is commonly used for long-term management of patients with severe psoriasis, short-term methotrexate administered in this manner cannot necessarily be recommended for severe widespread plaque-type disease. Measurement of methotrexate levels in a further 24 patients with severe psoriasis receiving 47 low-dose infusions revealed relatively constant and predictable methotrexate concentrations. Acute side-effects of methotrexate given by the infusion method were minor and uncommon, the infusion being well tolerated by patients. However, the low-dose infusion technique did not, apparently, offer any advantage over conventional methotrexate administration. PMID- 2591093 TI - Colchicine therapy in Behcet's syndrome--a report of five cases. AB - Five patients with Behcet's syndrome of varying duration were treated with colchicine (500 micrograms b.i.d.). All improved clinically and one has remained clear for 1 year after cessation of therapy, although in one patient who had neurological symptoms, paraesthesiae have persisted throughout treatment. PMID- 2591094 TI - Multiple clear cell acanthomas--treatment by cryotherapy. AB - Clear cell acanthomas (Degos' acanthomas) are usually solitary tumours and an excisional diagnostic biopsy therefore provides effective treatment. Such an approach is, however, impractical in the much rarer condition of multiple clear cell acanthomas where up to 30 lesions have been described on one patient. We describe a case of multiple clear cell acanthomas in which cryotherapy provided a quick and convenient method of treatment resulting in minimal scarring especially when compared to excision biopsy. PMID- 2591095 TI - Reticulate acropigmentation of Kitamura. AB - Reticulate acropigmentation of Kitamura in a mother and her daughter is reported. Both demonstrated peri-orbital involvement in addition to involvement of acral areas, face and eyelids which has not been recorded before. PMID- 2591096 TI - Carcinoma-associated dermatomyositis responding to plasmapheresis. AB - We report a case of severe carcinoma-associated dermatomyositis which, having shown no response to conventional treatment, improved markedly within 48 h of plasmapheresis. We believe that this is the first time that dermatomyositis associated with an advanced carcinoma has been reported to respond in this way. Dermatomyositis can prove extremely difficult to treat and sometimes fails to respond even to very high doses of steroids and immunosuppressants. There is currently only a single report of the use of plasmapheresis in adult dermatomyositis. We therefore wish to support the findings of Dau and draw attention to the value of this therapeutic option in refractory dermatomyositis. PMID- 2591098 TI - Sporotrichoid spread of cutaneous Mycobacterium chelonei infection. AB - Atypical mycobacterial infections of the skin have increased in frequency in immunocompromised individuals in recent years. Such patients may follow a different clinical pattern from immunocompetent patients, often lacking a history of preceding trauma and presenting with multiple suppurating subcutaneous nodules. A sporotrichoid pattern of spread may occur with the species Mycobacterium kansasii and M. marinum but is rare with M. chelonei. PMID- 2591097 TI - Thrombotic cutaneous nodules and hepatic vein thrombosis in the anticardiolipin syndrome. AB - A patient with the anticardiolipin syndrome presented with hepatic vein thrombosis (Budd-Chiari syndrome) and non-ulcerating, thrombotic, cutaneous nodules. This cutaneous manifestation of the anticardiolipin syndrome has not been described before, though its histological appearances resemble those of previously reported cutaneous complications, such as chronic ulceration, livedo reticularis and distal cutaneous ischaemia. Recognition of the skin lesion could allow the prevention of major systemic complications. PMID- 2591099 TI - Darkening of white hair in Parkinson's disease. AB - We describe a patient with long-standing Parkinson's disease who noted that his white hair turned grey and darkened 8 months after the addition of carbidopa to his established levodopa (L-dopa) therapy and 4 months after the introduction of bromocriptine. PMID- 2591100 TI - Extensive spinal hyperostosis in a patient receiving isotretinoin--progression after 4 years of etretinate therapy. AB - A patient with Darier's disease was discovered to have persistent, asymptomatic cervical and thoracic spinal hyperostoses after receiving isotretinoin for 7 years. The spinal abnormalities have remained asymptomatic but have now progressed following 4 years of etretinate therapy. The development of skeletal abnormalities, in particular spinal hyperostosis, is well-documented in patients receiving the synthetic retinoid, isotretinoin (Accutane, Roaccutane). The occurrence of extraspinal tendon and ligament calcification has been emphasized following long-term therapy with etretinate (Tegison, Tigason), but the relationship between etretinate and spinal hyperostosis is less certain, there being a need for a long-term, prospective, appropriately controlled investigation of patients receiving etretinate. We report a patient with Darier's disease who was discovered to have prominent, asymptomatic cervical and thoracic spinal hyperostoses after receiving isotretinoin for 7 years. Subsequent treatment with etretinate for 4 years did not prevent progression of the spinal abnormalities. PMID- 2591102 TI - Yellow nail syndrome associated with empyema. AB - The yellow nail syndrome is a rare condition consisting of slow-growing dystrophic nails and oedema, usually affecting the ankles, and probably due to defective lymphatic drainage. Its association with mild chronic pulmonary disease has been recognized. We describe a case initially complicated by a recurrent pleural effusion but, more importantly, by the development of bronchiectasis and thoracic empyema. PMID- 2591101 TI - Pityriasis rotunda in a Caucasian woman from the Mediterranean area. AB - Pityriasis rotunda (PR) has been known to affect, almost exclusively, Japanese and South African Bantu, often in association with various systemic diseases. However, the occurrence of PR in Caucasian patients is extremely rare, and has been previously described in only three reports. We hereby report a case of an apparently healthy Caucasian woman from Israel having clinical and histological features characteristic of PR. Pityriasis rotunda (PR) is a rare disorder of keratinization characterized by strikingly well demarcated, perfectly round scaly brownish patches of variable number and diameter located mainly on the trunk and extremities. The exact place of this disorder within the nosology of the cutaneous dermatoses is not yet fully established. However, most authors regard it as a special circumscribed form of acquired ichthyosis with a histological resemblance to ichthyosis vulgaris. For more than half a century following the first description of this disorder in 1906 cases reported were almost exclusively from the Far East, particularly from Japan, or in South African Negroids, with a few cases of West Indian Negroids, usually in association with various debilitating diseases. The first report of a Caucasian patient appeared in the literature in 1966 and since then there have been only two additional reports of PR in Caucasian patients. PMID- 2591103 TI - Aphthous ulcers responding to etretinate--a case report. AB - Aphthous ulcers are notoriously difficult to treat. We report repeated remission of recurrent aphthous ulceration in a female while taking etretinate for plantar pustular psoriasis. Although systemic retinoids are potent teratogens and are generally inappropriate for women of childbearing potential, this case report suggests further assessment of retinoids in severe aphthosis is warranted in selected patients. PMID- 2591104 TI - Nodules following hay fever desensitizing injections. PMID- 2591106 TI - V.D.R.L. test. PMID- 2591105 TI - Lupus erythematous profundus. PMID- 2591107 TI - Lichen planus and photo-onycholysis induced by quinine. PMID- 2591108 TI - Rheumatoid arthritis and the measurement properties of the physical ability dimension of the Stanford Health Assessment Questionnaire. PMID- 2591109 TI - Prevention of postmenopausal bone loss in rheumatoid arthritis patients. A two year prospective study. AB - The effect of three different therapeutic regimens on bone mineral content at the radius and lumbar spine was studied in a group of 60 postmenopausal rheumatoid arthritis patients. Results were compared to those in a group of controls matched for sex, age, disease duration and menopausal state. Serum and urinary parameters of calcium metabolism were also evaluated in the three treatment groups. The three treatment regimens were: 1 alpha hydroxyvitamin D + calcium + placebo; 1 alpha hydroxyvitamin D + calcium + lynestrenol; and 1 alpha hydroxyvitamin D + calcium + sodium fluoride. In all treatment groups there was a positive effect of therapy compared to controls, though this was only significant in the 1 alpha hydroxyvitamin D + calcium + lynestrenol group at the axial skeleton after 1 and 2 years of treatment. Serum calcium rose significantly in the 1 alpha hydroxyvitamin D + calcium + placebo group and serum creatinin was raised in all the treatment groups during therapy. In the 1 alpha hydroxyvitamin D + calcium + lynestrenol group, serum alkaline phosphatase activity and urinary hydroxyproline excretion decreased significantly. PMID- 2591110 TI - Dermal elastin and collagen in systemic sclerosis. Effect of D-penicillamine treatment. AB - Skin biopsies from 4 systemic sclerosis (SSc) patients, 6 SSc patients treated with D-penicillamine (from 8 to 60 months) and 4 normal subjects were analyzed by light and electron microscopy. By light microscopy, collagen bundles of SSc dermis were thicker and more compact than in age-matched controls; D penicillamine treatment did not significantly modify their organization. On the contrary, a stereological analysis showed that the elastin volume density was higher in patients than in controls, and increased again after D-penicillamine treatment: moreover, the number of elastin fibers per unit area was significantly higher in the dermis of patients compared to controls, and became even higher after D-penicillamine treatment. The phenomena were evident in all strata of the dermis; however, the most significant increase of elastin in SSc patients compared to controls was in the superficial dermis, whereas after D-penicillamine treatment, all the strata of the dermis showed a significant increase in the percentage of elastin and in the number of elastin fibers per unit area compared to untreated patients and to controls. There were no relationships between elastin increase and time from the onset of SSc or time and dose of D penicillamine treatment. At the ultrastructural level, collagen fibrils had rather heterogeneous diameters and formed more compact fibers, especially in the reticular and in the deep dermis of SSc patients compared to controls. After D penicillamine, collagen fibril diameters in three of 5 patients examined were statistically wider and more heterogeneous than in controls and in untreated patients, whereas in the other 2 subjects both the mean diameter and the distribution of the class diameter were similar to both controls and untreated patients. This could suggest a specific individual reaction to the drug. Elastin fibers were smaller, more numerous and polymorphous in all patients compared to controls. After D-penicillamine, elastin fibers became even more numerous and smaller than in untreated patients. There was no correlation between the number and size of the elastin fibers and the time or dose of D-penicillamine. The internal organization of the elastin fibers was normal. These data indicate that the amount and distribution of collagen and elastin are altered in the dermis of SSc patients, and that D-penicillamine interferes with the deposition of both fibrous proteins in the dermal extracellular space. PMID- 2591111 TI - Evidence of neuromuscular hyperexcitability features in patients with primary fibromyalgia. AB - The presence of clinical and electromyographic (EMG) features of neuromuscular hyperexcitability (NMHE) and of the commonly associated neurovegetative disturbances (NVD) were investigated in 49 patients with primary fibromyalgia (PF) and in a control group of 33 patients with rheumatoid arthritis (RA). At least two clinical features of NMHE were present in 39%, and at least three NVD in 63% of PF patients. In contrast, only 1 RA control had two NMHE features (p greater than 0.005) and three NVD (p less than 0.001). Moreover, a significant post-ischemic spontaneous EMG hyperactivity was observed in 11 PF patients, and in only 1 control with RA (p less than 0.05). Finally, in patients with PF the number of tender points were correlated with psychological tests for depression (p less than 0.02), and the number of NVD. The present study shows that in patients with PF there is a large prevalence of NMHE complaints and NVD. The potential underlying pathogenetic mechanisms are also discussed. PMID- 2591112 TI - Clinical subgroups and HLA antigens in Italian patients with psoriatic arthritis. AB - The frequencies of HLA antigens were studied in 101 Italian patients with psoriatic arthritis. The total group showed a significant increase in frequency of A1 and B38, and a reduction of B5 when compared to healthy controls. No association between DR and/or DQw antigens and PA were demonstrated. The comparisons between the clinical subgroups and normal controls revealed a significant association of B38 with asymmetric peripheral arthritis, B27 and B39 with spondylitis (with or without peripheral involvement). When intergroup comparison were made, the patients with spondylitis had an increase in frequency of B27 and DQw3 as compared to those with symmetric and asymmetric peripheral disease. DR4 and DRw53 were associated with earlier age of onset of arthritis. There were also significant associations between DQw3 and severe disease, and between A9, B5 and presence of erosions and joint space narrowing. No association with DR4 was showed in a subgroup of patients with symmetric polyarthritis without DIP involvement. PMID- 2591114 TI - Correlation of synovial fluid interleukin 6 (IL-6) activities with IgG concentrations in patients with inflammatory joint disease and osteoarthritis. AB - Synovial fluids of patients with rheumatoid arthritis, osteoarthritis, psoriatic arthritis, reactive arthritis and Reiter's syndrome were examined for their concentrations of interleukin 6 (IL-6) in a proliferation assay with the IL-6 dependent hybridoma cell line B13.29 (subclone B9). IL-6 activity was significantly higher in the synovial fluids of patients with rheumatoid arthritis and psoriatic arthritis than in patients with osteoarthritis. Significant correlations were shown between the concentrations of synovial fluid IL-6 and IgG. These findings may contribute to the understanding of the enhanced immunoglobulin production by synovial mononuclear cells in patients with inflammatory joint disease. PMID- 2591113 TI - Subcutaneous fat biopsy in the diagnosis of amyloidosis secondary to chronic arthritis. AB - Subcutaneous fat biopsy was investigated for its sensitivity in giving a diagnosis in 44 consecutive patients with rheumatoid arthritis or ankylosing spondylitis suspected of systemic amyloidosis. In 26 of these patients amyloidosis could be demonstrated by fat or rectal biopsy or biopsies from organs suspected of amyloid deposition. Fourteen of the 26 (54%) fat biopsy specimens of the patients with amyloidosis were positive after staining with Congo red and 22 (85%) of the rectal biopsy specimens were positive. All 12 kidney biopsy specimens and 4 biopsy specimens from other organs of these 26 patients were positive for amyloidosis. In 2 patients with a negative rectal biopsy specimen, fat biopsy would have obviated the need for a more invasive biopsy. All patients experienced fat biopsy as less demanding compared to other biopsy procedures. These results imply that in patients with chronic arthritis subcutaneous fat biopsy is a useful screening procedure. In this patient group fat biopsy is less sensitive for the diagnosis of amyloidosis compared to rectal biopsy. PMID- 2591115 TI - Septic arthritis of the pubic symphysis. AB - Septic arthritis of the pubic symphysis developed in a previously healthy 13-year old boy. Blood cultures and the culture of material taken by joint aspiration of the pubic symphysis under radioscopic control yielded Staphilococcus aureus. Early treatment with parenteral antibiotics prevented the development of osteomyelitis of the pubic rami in our patient. Open debridement was not necessary. PMID- 2591117 TI - Melkersson-Rosenthal syndrome in a patient with sero-negative oligoarthritis. AB - The Melkersson-Rosenthal syndrome is a rare disease consisting of orofacial swellings, facial nerve palsy and plicated tongue. The etiology is unknown. On histopathological examination a characteristic granulomatous inflammation is found. A case of this syndrome in a young white female with seronegative oligoarthritis is described and the possible relationship between the two diseases is discussed on the basis of the literature. PMID- 2591116 TI - Mutilans arthropathy in systemic lupus erythematosus. AB - The rare association of resorptive arthropathy with systemic lupus erythematosus is described in a 37-year-old female patient in order to emphasize the occurrence of aggressive joint abnormalities of the disease. This patient developed mild articular manifestations at the onset of the disease and 8 years later we detected mutilans changes in the DIP joints. Other diseases in which similar articular findings have previously been noted, were ruled out through the follow up. PMID- 2591118 TI - Massive splenomegaly in systemic lupus erythematosus. PMID- 2591119 TI - Antiphospholipid antibodies in a Brazilian population with systemic lupus erythematosus. PMID- 2591120 TI - First International Symposium on Pediatric Rheumatology. Paris, July 21-22, 1989. Abstracts. PMID- 2591121 TI - Vitamins A and E, retinol binding protein and zinc in rheumatoid arthritis. AB - Serum vitamins A (2.0 +/- 0.7 mumol/l; p less than 0.05) and E (17.7 +/- 8.2 mumol; p less than 0.001) levels were lower in patients with rheumatoid arthritis (RA) than in healthy controls (2.3 +/- 0.6 mumol/l and 25.3 +/- 5.4 mumol/l, respectively). Low vitamin A and E levels together with a marginally lowered selenium concentration may lead to a markedly decreased antioxidant capacity and enhanced eicosanoid production in RA. Univariate linear regression analysis showed a positive correlation (r = 0.383; p less than 0.005) between serum levels of vitamin A and zinc, and between serum retinol binding protein (RBP) and zinc (r = 0.440, p less than 0.02). These findings suggest that hypovitaminosis A in RA may be mediated by decreased vitamin A transport from the liver to the blood, caused by the low level of zinc dependent hepatic retinol binding protein synthesis. In multiple linear regression analysis, the serum zinc level emerged as the most significant variable and had an independent predictive value of 15.2% for vitamin A. Variations in the serum vitamin E levels were only explained by seropositivity (predictive value of 14.2%), a finding which suggests that the decreased level of vitamin E is a constant feature in RA rather than part of the acute phase response. PMID- 2591123 TI - Inter-relations between clinical parameters and muscle function in patients with primary fibromyalgia. AB - In forty-four female patients with primary fibromyalgia, muscle function was related to clinical parameters such as age, height, number of tenderpoints, subjective scores of physical capacity and number of subjective symptoms. Muscle function was determined as the dynamic muscle strength measured with an isokinetic dynamometer. Muscle function was found to be low in primary fibromyalgia patients with pronounced muscle tenderness compared to matched controls. Furthermore the reduction in muscle function increased with increasing number of tenderpoints and subjective symptoms. In primary fibromyalgia patients correlations between muscle strength and age/height were either not present or were weaker than in the control subjects. It is concluded that voluntary dynamic muscle strength is a useful parameter for measuring disease impact in primary fibromyalgia patients. PMID- 2591122 TI - Humoral immunity and composition of immune complexes in patients with rheumatoid arthritis, with special reference to IgE-containing immune complexes. AB - IgE-containing circulating immune complexes (IgE-CIC) were determined with a 2.5% PEG-precipitation assay in 98 patients with classical or definite rheumatoid arthritis (RA). Of the 45 IgE-CIC positive sera, only 4 had elevated total serum IgE. IgE-CIC positive patients had more active disease than patients without IgE CIC, as determined by their more swollen joints and higher Ritchie indices (p less than 0.04 and 0.02, respectively). Apart from IgE, other immunoglobulin isotypes, rheumatoid factor (RF) of the IgG-, IgA- and IgM-classes, C3 and antinuclear antibodies could be demonstrated in the IgE-containing PEG precipitates. IgE-RF could not be demonstrated in serum or in IgE-CIC. Anti-IgE of the IgM-class (IgMaIgE) were frequently found (28/45 patients) in the IgE positive PEG-precipitates. All 14 patients positive for IgGaIgE in the IgE-CIC were also positive for IgMaIgE in the CIC. As in the serum, there was a good correlation in the CIC between the level of IgGaIgE and the level of IgMaIgE (r = 0.64). The correlation between the respective levels of IgGaIgE and IgMaIgE in serum and in CIC was high (r = 0.93 and 0.79, respectively). On the other hand, only 1 patient was positive for IgAaIgE in the IgE-CIC. We conclude that IgE and aIgE of the IgM- and IgG-classes are frequently present in the immune complex form in RA and that they are correlated with the clinical activity of arthritis. PMID- 2591124 TI - Subclinical involvement of the gut in undifferentiated spondylarthropathies. AB - In order to evaluate the frequency of subclinical gut involvement in the seronegative spondylarthropathies, ileocolonoscopy with biopsies of the colon, ileocecal valve and ileum were performed on 211 patients with ankylosing spondylitis (AS), reactive arthritis (ReA) and undifferentiated spondylarthropathies. Inflammatory gut lesions were detected in a large number of these patients. It was concluded that the group of undifferentiated spondylarthropathies could be split into fairly equal subgroups: one subgroup suffering from subclinical inflammatory bowel disease associated with peripheral joint symptoms, a second subgroup presenting a form of enterogenic ReA, and a third subgroup in which no relation with the gut could be demonstrated. Ankylosing spondylitis, which has to be considered as a form of undifferentiated seronegative spondylarthropathy, could be subdivided into the same subgroups. These findings confirm the existence of subclinical gut involvement in patients with seronegative spondylarthropathies. PMID- 2591125 TI - Nd:YAG laser modulation of synovial tissue metabolism. AB - In studies designed to establish the safety and efficacy of laser treatment of arthritis, the in vitro effect of Nd:YAG laser radiation on normal, osteoarthritic and rheumatoid synovial tissue and synovial fibroblast metabolism has been addressed. Defined energy levels of normal pulsed radiation (TEMoo mode) consistently up-regulated synovial tissue explant culture hyaluronic acid and protein synthesis. In contrast, high intensity Q-switched delivery down-regulated the response. The application of normal pulsed radiation had a variable effect on synovial fibroblast synthesis but the response of any given cell isolate was consistent. DNA synthesis and cell viability were not affected. PMID- 2591127 TI - NAD synthesis and ADPR transferase activity in blood lymphocytes of patients suffering from rheumatoid arthritis and of control persons. AB - NAD acts not only as a coenzyme in oxidation-reduction processes but also as substrate for adenoribosylation of different proteins. Patients suffering from rheumatoid arthritis show a disturbance in their tryptophan metabolism. Since tryptophan represents a precursor of NAD we turned our attention to the activity of the ADPR transferase, being the enzyme of adenoribosylation, as well as to the synthesis of NAD derived from nicotinamide in human lymphocytes. Lymphocytes of patients with rheumatoid arthritis did not show any differences in their activities as compared with those of control persons, regardless of different measures applied to the patients. PMID- 2591128 TI - Rheumatoid arthritis and chronic lymphatic leukaemia. AB - There is evidence for an increased incidence of lymphoproliferative disorders in patients with rheumatoid arthritis (RA). We present the clinical features of 4 patients with RA and chronic lymphatic leukaemia (CLL) which, occurring in a population of 1505 RA patients, represents a significantly increased prevalence of CLL (p less than 0.05) compared to the general population. These patients had significantly lower natural killer cell activity than matched rheumatoid controls (p less than 0.05) or normal controls (p less than 0.01) and we discuss this as a possible mechanism of association. PMID- 2591126 TI - Altered lymphocyte proliferation by low dosage laser irradiation. AB - The effect of gallium-aluminum-arsenide laser irradiation on the proliferation of human lymphocytes in culture in response to mitogenic stimulation by phytohemagglutinin was investigated. Mitogenic proliferation was inhibited by the laser irradiation at a low energy fluence and enhanced at a high energy fluence. The results indicate that low-watt laser irradiation can interfere with the immune response in vitro, and similar interference could occur in patients with rheumatoid arthritis subjected to laser therapy, if an appropriate dosage is chosen. PMID- 2591129 TI - Polydermatomyositis with anti-PL7 antibody: clinical and laboratory follow-up over a five year period. AB - Anti-PL7 antibodies to threonyl-tRNA synthetase purified from beef liver were observed in the serum of a dermatopolymyositis patient. They were identified by CIE and DID using a standard anti-PL7 antiserum and quantified by ELISA in serum samples taken over a five year period. The level of antibodies against not only threonyl-tRNA synthetase but also several muscle proteins including tropomyosin, was strongly correlated with disease activity and treatment. This correlation may prove important both in monitoring the response of the patient to treatment and to our understanding of the aetiology of the disease. PMID- 2591130 TI - Two familial cases of malignant Reiter's syndrome. AB - A Cambodian man and his son concomitantly developed malignant Reiter's syndrome soon after their arrival in France. In both cases generalized skin lesions of pustular psoriasis and systemic features were present. The son died after 2 years of unresponsive continuously progressive disease. The father received pulses of high dose immunosuppressants that worked rapidly and prevented a life threatening course. These 2 cases illustrate the pathophysiologic hypothesis of Reiter's syndrome, emphasizing the role of environmental triggering factors and the relationship between spondylarthropathies in B27 positive patients. Fatal cases of Reiter's syndrome are very rare in the review of the literature. PMID- 2591132 TI - Recurrent deep vein thrombosis, thromboembolic pulmonary hypertension and the 'primary' antiphospholipid syndrome. PMID- 2591131 TI - Serum IGF-I levels and growth failure in juvenile chronic arthritis. AB - The association between growth failure and serum IGF-I levels has been assessed in 32 children with Juvenile Chronic Arthritis (JCA) aged 5-16 years. A spectrum from normal growth to severe growth failure was included in the study population. Height Standard Deviation Score (SDS) ranged from -5.79 to +1.41 (median -1.22) and Height Velocity from 0.72-8.85 cm/yr (median 3.81 cm/yr). Known risk factors for growth failure (disease activity, steroid treatment, vertebral collapse) were confirmed. Additionally, height SDS was significantly correlated with serum IGF-I levels (rs = 0.49; p = 0.008); height velocity was significantly, although less strongly correlated with IGF-I levels (rs = 0.41; p = 0.027). There was no correlation between IGF-I levels and either of two indices of nutritional status, or between IGF-I levels and current steroid dose. The correlation of serum IGF-I with parameters of growth failure may be due to either insufficient secretion of growth hormone (GH) or defective GH action. In view of the recently increased availability of GH for treatment of short stature, it is important to distinguish between these two mechanisms. PMID- 2591133 TI - Development of uveitis and arthritis in a child with focal glomerulosclerosis. PMID- 2591134 TI - Primary Sjogren's syndrome (SS) with inappropriate antidiuretic hormone secretion (SIADH). PMID- 2591135 TI - Idiotypic independency of anti-dsDNA and anti-Sm antibodies in SLE sera. PMID- 2591136 TI - Canadian Cardiovascular Society. 1989 scientific program and abstracts. Vancouver, British Columbia, October 25, 26, 27, 28, 1989. PMID- 2591137 TI - Abstracts. French-German joint meeting for neuropathology. Frankfurt/Main, October 19-21, 1989. PMID- 2591138 TI - Ethical considerations in the conduct of clinical pharmacokinetic studies. PMID- 2591139 TI - Release of gentamicin from acrylic bone cement. AB - The pharmacokinetics of gentamicin were studied after total hip joint arthroplasties performed with "Palacos R plus gentamicin' in 10 patients. Urine was collected at 12-hour intervals for 15 days after operation, and drainage fluids for 48, 72 or 108 hours. Blood samples were taken 3 and/or 5 hours after prosthesis implantation. High concentrations of gentamicin were found in drainage fluids. Excretion curves in drainage fluids or urine were fitted by a computer aided design program (SIAM) and the mean curves established. Elimination of gentamicin was biphasic in both cases. The rapid phases had a half-life of 2.97 hours in drainage fluids and 7.16 hours in urine. Half-lives of the slow phases were 13.5 and 47.12 hours, respectively. The mean percentage of total gentamicin released by the two routes was 5.78% of the quantity implanted. The calculated peak blood concentration was 0.12 mg/L. It is concluded that gentamicin concentrations locally reach levels higher than minimum inhibitory concentrations of most of the likely pathogens in patients undergoing total hip joint arthroplasties with "Palacos R plus gentamicin' bone cement. However, as blood concentrations appear to be low, patients may not be protected against systemic infections. PMID- 2591140 TI - Critical issues in intrapartum and delivery room management. PMID- 2591141 TI - [A rare manifestation of Echinococcus cysticus in CT and magnetic resonance tomography]. AB - A case of primary spinal echinococcus with bone destruction is presented and the findings in CT and MR imaging are discussed. Although CT and MRI are complementary studies for the diagnosis of the spinal echinococcosis, MRI is the study of choice for prolonged follow-up of complicated cases. PMID- 2591142 TI - [Generalized brain edema and cerebral infarct in ergotamine abuse: imaging by computerized tomography, magnetic resonance tomography and angiography]. AB - Abuse of ergotamine can release a generalised brain edema and brain infarctions. This can be visualized by CT, MR and angiography. The reason, however, can only be found in the patients history. PMID- 2591143 TI - [The value of computerized tomography in detecting and localizing lung metastases]. AB - 25 patients with an extrathoracic malignant tumor and radiologically proven lung nodules had a thoracic CT preoperatively. 111 nodules were confirmed by surgery (median: 10 mm). Histopathological examination revealed 104 metastases or sterilised metastases and 7 benign nodules. CT detected 97% of the nodules. Localisation of the nodules according to different lobes or segments was correct in 97% of nodules. CT is a very sufficient method for the detection and localisation of lung metastases. PMID- 2591144 TI - CT of primary retroperitoneal soft tissue masses. AB - CT scans of 54 patients with primary peritoneal soft tissue masses were studied retrospectively. All lesions were untreated at the time of the CT examinations and the nature of the lesions was subsequently proven histologically. Each scan was evaluated initially without knowledge of clinical and pathological information in respect of several criteria including size and number of lesions, delineation of the lesions, border definition, and internal structure of the lesions. The lesions were demonstrated in all patients and displayed with great anatomical detail. The presence of gas and attenuation values below -30 HU were the only singular signs specifically indicative of abscesses or lipomatous tumors, respectively. All other applied criteria were found both in sarcomas and benign masses, and no malignant neoplasm had CT characteristics specific enough to differentiate it from any other one. Considering all criteria, the benign or malignant nature of the lesions could be predicted in 43% of the patients studied based solely on CT morphology. In context with the clinical information provided on the study request form, 54% of the lesions were correctly classified into aetiological sub-groups (i.e. soft tissue sarcoma, abscess). PMID- 2591145 TI - [Hysterosalpingography with digital image intensification radiography]. AB - Digital image intensifier radiography (Siemens/Polytron) offers the chance to reduce patient exposure dose in hysterosalpingography (HSG) by 85% compared with conventional film/screen radiography and by 11% compared with the 100 mm technique. By appropriate choice of the parameters the signal-to-noise ratio was adapted to the detectability of the diagnostic information (variation of the dose). Thirty patients were examined with the 28 cm image intensifier and an image intensifier input dose of 50 microR. The diagnostic image quality was assessed being aware of the results of laparoscopy or surgery; in 29 cases the quality was classified very good without any limitations. Digital image intensifier radiography offers additional advantages over conventional x-ray units: the images are directly available on the monitor and offer the possibility of post-processing. PMID- 2591146 TI - [3-dimensional reconstructions of the skull, axial and extremity skeleton]. AB - In a prospective study, 150 threedimensional reconstructions of patients with bone diseases were analyzed. It could be seen that 3 D images were relevant for therapeutic considerations in diseases of craniofacial bones, and to a lesser degree for other skeletal regions. In no case was the 3 D reconstruction the only important factor for the therapeutic decision. The study demonstrated that 3 D imaging of the pelvic bones, especially for necroses of the femoral head, is severely limited without the possibility of computer-aided disarticulation. PMID- 2591147 TI - [Arterial angio-CT and magnetic resonance tomography of Klatskin tumors]. AB - The knowledge of the exact spreading and location of a malignant bile duct tumor and the exclusion of differential diagnoses are the prior conditions for the development of an optimal therapy concept. All usual methods such as ERCP, PTC, ultrasound, CT and angiography have weak points in the diagnosis of Klatskin tumors. A new aspect for the solution of this problem is the ability to visualize these tumors by arterial angio-CT and MR. PMID- 2591148 TI - Combination chemotherapy with conservative obstetric management in the treatment of pregnant patients with acute myeloblastic leukaemia. AB - We have reviewed the management of pregnant women presenting with acute myeloblastic leukaemia (AML) at the London Hospital since 1972. Six women in the second or third trimester were diagnosed with AML over this period. One woman had termination of pregnancy at presentation in the second trimester. Three of the remaining five patients achieved complete remission following chemotherapy during pregnancy. Delivery was achieved by the vaginal route in three and by caesarean section in one patient. All were livebirths but one infant had Down's syndrome. Median maternal survival was 16 months (range 0-44 months). Long-term survival was achieved for both mother and infant in only one case. Longer maternal survival was seen in patients treated in the period 1980-1985. Increased survival appears to be related to the introduction of more aggressive chemotherapy schedules and improved supportive care. PMID- 2591149 TI - One-shot high-dose pamidronate disodium (APD): effective, simple treatment for hypercalcaemia in haematological malignancy. AB - Fifteen patients with haematological malignancy and hypercalcaemia (mean +/- SEM calcium 3.44 +/- 0.14 mmol/l) received pamidronate (1 mg/kg) by infusion on 17 occasions (two patients were retreated 2 and 6 months after the first dose). After 4 days the plasma calcium had fallen to 2.84 +/- 0.14 mmol/l (P less than 0.001; n = 17), and in 10/17 episodes was less than 2.6 mmol/l. The mean fall was 0.61 mmol/l (95% confidence intervals 0.49-0.72 mmol/l). By 7 days a further decrease to 2.53 +/- 0.10 mmol/l had occurred, continuing to 2.38 +/- 0.11 mmol/l after 14 days. Plasma phosphate fell from 1.18 +/- 0.16 to 0.74 +/- 0.07 mmol/l at 7 days (P less than 0.001; n = 12). In 9 of the 17 episodes plasma creatinine initially exceeded 120 mumol/l (four of these greater than 300 mumol/l). This did not impair the response to pamidronate and there was no significant change in plasma creatinine following treatment. A single large dose of pamidronate was a simple, well-tolerated and very reliable treatment for hypercalcaemia complicating haematological malignancy, irrespective of renal function. PMID- 2591150 TI - Pulse oximetry in sickle cell disease. AB - The place of pulse oximetry in monitoring arterial oxygen saturation in sickle cell disease has been evaluated. In four admissions of patients with sickle cell anaemia with varying degrees of arterial haemoglobin oxygen desaturation, pulse oximetry was compared with a simultaneous assessment of oxygen saturation by arterial blood gas measurement and oxygen dissociation curve (ODC) analysis. Close agreement was found between the oxygen saturation measured by pulse oximetry and that calculated from the measured arterial partial pressure of oxygen (PaO2) with reference to the patient's own ODC. Calculation of oxygen saturation by the blood gas analyser assuming a normal ODC was erroneous. Pulse oximetry is an accurate and effective non-invasive method for monitoring the arterial oxygen saturation in sickle cell disease. PMID- 2591151 TI - Response to desmopressin in type IID von Willebrand's disease. AB - Dominant transmission of a variant of von Willebrand's disease (vWD) with aberrant polymerization of von Willebrand factor (vWF) has been identified in a Scottish family. Multimer analysis of plasma vWF from the propositus and her father revealed an identical pattern to that previously reported in families designated as type IID vWD. There is loss of the larger multimers and presence of an intermediate subsidiary band not seen in normal subjects or other vWD variants. Platelet/vWF interaction induced by ristocetin is not enhanced in these cases and the platelet vWF shows the same aberrant multimer pattern as plasma vWF. DDAVP infusion in two affected members of the Scottish family and in one of the index cases produced a rise in plasma vWF antigen and factor VIII. Higher molecular weight vWF multimers appeared transiently after infusion of desmopressin (1-deamino-8-D-arginine vasopressin, abbreviated DDAVP) coincident with shortening of the bleeding time. The platelet counts did not change after the DDAVP infusions. DDAVP should be considered for management of bleeding in this variant of von Willebrand's disease. PMID- 2591152 TI - Safety of invasive procedures in patients with the coagulopathy of liver disease. AB - To assess the need for prophylactic fresh frozen plasma in patients with chronic liver disease before procedures, we followed 39 consecutive patients with prothrombin times (PT) of 15-29 s who had 71 invasive procedures. A total of 57 procedures was done in 30 patients receiving no blood product support, while 12 patients received blood products within 12 h of 14 procedures. Only three of the latter group received fresh frozen plasma prophylactically to improve the PT. The two groups were similar in the severity of their liver disease. There were nine surgical procedures as well as paracenteses, thoracenteses, lumbar punctures, and central venous line placement. Three bleeding episodes occurred. Two of the bleeding episodes required no further treatment. Because of the low incidence of bleeding and the ease in controlling the bleeding once it occurred, fresh frozen plasma is not recommended for prophylaxis of an elevated prothrombin time. PMID- 2591153 TI - Blood usage for elective surgery. A reappraisal of the need for autologous transfusion. AB - To assess the need for a pre-operative autologous transfusion programme in a large teaching hospital, a review of blood cross-matching and transfusion practice for three elective surgical procedures was undertaken. For hysterectomy, the cross-match rate was 28%, and the transfusion rate only 8%. For transurethral resection of prostate and hemicolectomy, all patients were cross-matched, but only 19% and 36%, respectively, transfused. Given these figures, an autologous transfusion programme was not felt to be cost-effective. Local audit is necessary before this can be ascertained for a given district, as is consideration of the likelihood of infectious hazards in the regional blood supply. PMID- 2591154 TI - Transfusion of ABO-incompatible platelets causing severe haemolytic reaction. AB - Not infrequently clinical demand dictates that patients receive transfusions of ABO-incompatible platelets when there is a short supply of group-specific platelets. This carries a risk of causing a haemolytic reaction, as illustrated in the clinical case we report. In discussing this potential complication, we suggest a strategy for avoiding it. PMID- 2591155 TI - Safety of the abbreviated cross-match in association with sensitive serum screening. AB - The satisfactory outcome of 6 years experience with the abbreviated cross-match and pretransfusion serum screening are described. Antibody detection and identification were improved by using microplates rather than tubes. PMID- 2591157 TI - Counting reticulocytes by flow cytometry: use of thiazole orange. AB - Thiazole orange is a new fluorescent dye which will bind to the residual RNA in the cytoplasm of reticulocytes and allow their enumeration by FACS analysis. We have evaluated the use of this dye in the routine haematology laboratory. There is an excellent correlation between manual and FACS reticulocyte counts (r = 0.98) but FACS counting showed significantly higher precision (CV = 3.1) than the manual method (CV = 11.9) for single observer, 20.8% for multiple observers). Clinical specimens showed stable reticulocyte counts for 6 h if stored at 4 degrees C allowing efficient batching of samples. There was a significant fall in reticulocyte counts stored for 24 h at both 4 degrees C and 21 degrees C. Evaluation of 78 male and 76 female blood donors by FACS analysis gave normal ranges (mean % +/- 2 SD) of 0.74 +/- 0.48 and 0.84 +/- 0.56 respectively (P less than 0.005). When corrected to absolute values there was no sex difference (36 +/ 24 x 10(9)/l). Thiazole orange is an effective stain for the automated counting of reticulocytes by FACS analysis. PMID- 2591156 TI - An evaluation of the Coulter VCS differential counter. AB - An evaluation of the Coulter VCS (volume, conductivity, light scatter) automated differential counter demonstrated satisfactory correlations with manual 800-cell differential counts for neutrophils, lymphocytes, monocytes and eosinophils. For the detection of abnormal cells, 12.2% of samples gave false-negative results on the VCS, and 13.4% gave false-positive results. However, only 0.8% of the false negatives would be expected to be picked up by a standard 100-cell manual differential count. Carry-over accorded to manufacturer's specifications and throughput was 60 samples/h. Reference normal ranges have been established and the instrument's precision and performance with leucopenic and neonatal blood samples assessed. PMID- 2591158 TI - Acute renal failure in paroxysmal nocturnal haemoglobinuria with splanchnic venous thromboses. PMID- 2591160 TI - Cerebral Hodgkin's disease and progressive multifocal leucoencephalopathy. PMID- 2591159 TI - Acute monocytic leukaemia and t(2;6) (p21;q26) translocation. PMID- 2591161 TI - Absorption of ferric maltol, a novel ferric iron compound, in iron-deficient subjects. PMID- 2591163 TI - Diagnostic enzymology. PMID- 2591162 TI - Extramedullary disease initially without bone marrow involvement in acute promyelocytic leukaemia. PMID- 2591164 TI - Legal aspects of laboratory medicine. AB - Societal expectations of modern laboratory medicine will engender increasing scrutiny about the accuracy of laboratory data, the timeliness of performing laboratory tests, and the transmission of the results. Laboratorians who understand basic medicolegal principles applicable to laboratory medicine will be comfortable at the interface between law and medicine, and likely will practice acceptable laboratory medicine. Good medicine is good law. The authors divide their discussion into four parts: accountability for laboratory services, quality and risk in laboratory management, forensic evidence in the laboratory, and testimony by clinical laboratory personnel. PMID- 2591166 TI - The application of molecular and immunologic techniques to study the epidemiology of Legionella pneumophila serogroup 1. AB - We applied monoclonal antibody typing and restriction endonuclease analysis of plasmid DNA to study 28 clinical and 35 environmental (potable water) isolates of Legionella pneumophila serogroup 1 from three hospitals in Iowa between 1981 and 1986. Monoclonal antibody typing employed a panel of seven antibodies and delineated eight different subtypes. Plasmids were present in 57% of the isolates including 12 of 28 (43%) clinical and 25 of 35 (69%) potable water isolates. The plasmids ranged in size from 28 to 98 kilobase pairs and comprised eight distinct subtypes by restriction endonuclease analysis with Eco RI. Combination of monoclonal antibody and restriction endonuclease subtyping (composite subtyping) revealed 19 different composite subtypes of Legionella pneumophila serogroup 1. The most common composite subtype, 09:04, comprised 29% (18 of 63) of the isolates and was only found in clinical and potable water samples from a single pavilion in hospital A during an outbreak of Legionella pneumophila serogroup 1 pneumonia. Aside from this cluster the diversity of composite subtypes of Legionella pneumophila serogroup 1 observed in clinical and potable water sources over the 5-year period was striking. The combination of monoclonal antibody and restriction endonuclease typing resulted in improved strain delineation and a more useful use of epidemiologic markers for Legionella pneumophila serogroup 1. PMID- 2591165 TI - High incidence of false positives by a latex agglutination test for the diagnosis of Clostridium difficile associated colitis in compromised patients. AB - Detection of Clostridium difficile cytotoxin using cell culture assays for the diagnosis of antibiotic-associated colitis has been used for over a decade. Because the methodology is time consuming and cumbersome, a recently introduced commercial latex agglutination (LA) kit has attracted much attention. We compared the sensitivity and specificity of this method with the cytotoxic assay (CTA) using diarrheal stools from 652 patients at a referral tertiary care center. Specimens from 71 (10.9%) patients were found positive with CTA and 98 (15%) by LA. Of these, 67 stools were positive by both methods. Four specimens showed cytotoxicity but were negative by LA. Of the 31 patient specimens that were positive by LA but negative by CTA, 22 were obtained from leukemic bone marrow transplant and four from renal transplant patients [corrected]. Sixteen of these patients had Giardia lamblia (four), Salmonella enteritidis (three), Blastocystis hominis (five), Rotavirus (two), and Shigella boydii (two) in their stools [corrected]. No significant organisms were found in the rest of the LA-positive and CTA-negative specimens. PMID- 2591167 TI - Evaluation of four mycobacterial blood culture media: BACTEC 13A, Isolator/BACTEC 12B, Isolator/Middlebrook agar, and a biphasic medium. AB - Four commercially available mycobacterial blood culture systems were compared for sensitivity and time to detection of growth. A 5-ml volume of SPS-anticoagulated blood was cultured in a BACTEC 13A vial and a modified M7H11/BHI biphasic medium. In addition, two aliquots of Isolator concentrates, each derived from 5 ml of blood, were inoculated into a BACTEC 12B vial and onto a pair of Middlebrook 7H11 agar plates (M7H11). Mycobacteria were recovered from 32 of 180 cultured specimens (17.8%). Growth was detected in 30 (93.7%) of the 13A vials, 27 (84.4%) of the M7H11 agar plates, 26 (81.2%) of the 12B vials, and 14 (43.8%) of the biphasic bottles. The mean times to growth detection in the 13A vial (14.2 days) and the 12B vial (13.7 days) were shorter than in either the M7H11 plates (20.8 days) or the biphasic medium (24.1 days). When the Isolator/12B vial-and-M7H11 plates were evaluated as a single system, 29 cultures (90.6%) had a mean time to growth detection of 13.5 days. Colony-forming units per ml were inversely associated with time to growth detection. Delay in transport (greater than 24 h) appeared to reduce viability. The direct inoculation feature makes the 13A vial very suitable for mycobacterial blood cultures. PMID- 2591168 TI - Detection of multiple viral agents in nasopharyngeal specimens yielding respiratory syncytial virus (RSV). An assessment of diagnostic strategy and clinical significance. AB - A retrospective study of 6 years (1981-1987) experience with clinical specimens of pediatric patients submitted for identification of respiratory viruses was undertaken to determine the prevalence of multiple viral isolates and to assess the impact of dual infections on severity of clinical disease. Respiratory Syncytial Virus (RSV), the most frequently identified agent, was detected in cell culture and/or by immunofluorescence (IF) in 666 of 2,415 specimens examined. A second virus was isolated in cell cultures from 51 of the 666 specimens (7.6%). Cytomegalovirus, rhinoviruses, adenoviruses, influenza and parainfluenza viruses, echoviruses, vaccine strain polio viruses, and herpes simplex virus were identified with RSV. The diagnosis of a dual viral infection would have been missed in 37 of 51 instances (79%) had rapid diagnosis for RSV been employed without inoculation of cell cultures. Demographics and clinical presentations were similar in patients with dual infections or RSV alone. A case-control study comparing patients with dual isolates and patients with RSV alone to determine the effect of multiple viral infections on severity of disease revealed no significant difference. The combined use of rapid methods and isolation in culture provides more complete viral diagnosis and could have an impact on the choice of antiviral agents and the institution of appropriate infection control measures. PMID- 2591169 TI - Agrobacterium radiobacter and CDC group Ve-2 bacteremia. AB - Agrobacterium radiobacter and CDC Group Ve-2 are rare human pathogens. The simultaneous infection with both of these bacteria in an immunocompromised host is reported. Review of the UCLA microbiology laboratory records revealed one additional case of A. radiobacter bacteremia and two additional cases of CDC Group Ve-2 bacteremia over a 3-year period. The clinical experience with these organisms is reviewed. Both organisms are opportunistic pathogens with a predilection for patients with foreign bodies in place. Although CDC Group Ve-2 bacteremia may respond to antibiotic therapy alone, the cure of A. radiobacter infections often requires foreign body removal. PMID- 2591170 TI - Varicella associated intracerebral hemorrhage in the absence of thrombocytopenia. AB - A young woman with varicella complicated by streptococcal cellulitis developed an intracerebral bleed in the absence of thrombocytopenia, serious coagulopathy, or a detectable vascular lesion. We postulate that during the acute infection with varicella, a cerebral endothelial lesion was produced which later caused the intracerebral bleed. PMID- 2591171 TI - Should novobiocin be clinically re-evaluated? AB - The current novobiocin spectrum of antimicrobial activity was evaluated by testing 585 staphylococci (393 oxacillin-resistant) and 779 other bacterial strains. Novobiocin inhibited 98.5% of all staphylococcal isolates (MIC 90, 0.25 micrograms/ml) and a significant number of other Gram-positive species at less than or equal to 1 microgram/ml. Pathogenic Neisseria, Haemophilus influenzae, and Branhamella catarrhalis were also very susceptible to novobiocin, e.g., MIC 100, less than or equal to 1 microgram/ml. These results indicate that novobiocin may have a role in contemporary chemotherapy of oxacillin-resistant staphylococcal and other infections. PMID- 2591173 TI - Sulbactam: secondary mechanisms of action. AB - Light and scanning electron microscopy showed that 0.25, 0.5 and 1 times the minimum inhibitory concentrations (MICs) of sulbactam (SULB) caused filament formation in different species of Enterobacteriaceae, while 2 and 4 times the MICs caused spheroplast formation and subsequent lysis. By using a competitive assay with 125I-penicillin X, SULB showed a primary affinity for the PBP 1a and PBP3 of Escherichia coli, as well as for the PBP1a of Proteus mirabilis. The bactericidal interaction of human polymorphonuclear leukocytes (PMN) and SULB against E. coli K-1 resistant to the bactericidal activity of human serum was studied in vitro; however, SULB concentrations showed variations in the medium according to human kinetic data. Under these conditions, bacterial growth occurred in Hanks balanced salt solution containing SULB, PMN, or SULB-PMN in combination. In addition, bactericidal activity was observed in serum, with a killing rate of 90% for PMN or SULB, and 95% for SULB-PMN in combination. The postantibiotic enhancement of PMN bactericidal function was assessed against E. coli K1 pretreated with 0.5 the MIC of SULB (32 micrograms/ml) for 0.5 hr. The 90% bacterial killing rate of PMN occurred by 1.5 hr for pretreated bacteria and by 2.5 hr for untreated bacteria. Furthermore, the luminol-enhanced chemiluminescence (CL) assay using an E. coli stimulus showed that SULB does not modify PMN activity. PMID- 2591172 TI - Mechanism of beta-lactamase inhibition: differences between sulbactam and other inhibitors. AB - Three different types of beta-lactamases--TEM-2 type penicillinase, a typical cephalosporinase of Citrobacter freundii, and a Proteus vulgaris cephalosporinase with broad substrate range--were studied to determine the inactivation and reactivation kinetics for beta-lactamase inhibitors of these enzymes. Sulbactam, cloxacillin sulfone, clavulanic acid, imipenem, and aztreonam were evaluated. On the basis of the kinetic parameters a minimum scheme for the inactivation of these beta-lactamases by each compound was proposed, and the difference in the features of each of these as progressive and competitive inhibitors were evaluated. The relationship between the kinetic parameters and the synergistic effects of the inhibitors in combination with traditional beta-lactam antibiotics on the bacterial strains producing these beta-lactamases was examined. A close relationship between the synergistic effect, expressed as the FIC index, and a proposed parameter, TN x Ki/Km, was demonstrated. The results of this analysis suggest that sulbactam is a beta-lactamase inhibitor applicable to a wide range of beta-lactamase types. PMID- 2591174 TI - Antibiotic resistance in Australia with special reference to sulbactam/ampicillin. AB - A survey of antibiotic resistance in Australian states was undertaken by the Microbiology Quality Assurance Program of the Royal College of Pathologists of Australasia. Data were obtained from hospitals and private pathology laboratories serving both in-patients and out-patients at community hospitals. The study showed that resistance varied from state to state; it was highest in the Eastern states of New South Wales, Victoria, and Queensland, and lowest in Tasmania and Western Australia. In South Australia, isolates of Escherichia coli demonstrated a high degree of cefoxitin resistance. Western Australia and Tasmania showed high levels of gentamicin resistance for Klebsiella spp., as well as trimethoprim resistance in Proteus mirabilis. The relationship between erythromycin resistance and clindamycin resistance also differed among various states. These studies demonstrated the activity of sulbactam/ampicillin against a wide variety of common pathogenic bacteria in which resistance was mediated by beta-lactamase. PMID- 2591175 TI - Patterns of resistance to anaerobic organisms in Australia. AB - This study investigated patterns of resistance in anaerobic organisms isolated at Westmead Hospital in Sydney, Australia, during the years 1987 to 1988. Minimal inhibitory concentrations (MICs) to ampicillin, sulbactam/ampicillin, metronidazole, clindamycin, and cefoxitin were determined by agar dilution for 200 anaerobes from clinically significant infections. Antibiotics active against nearly all of these anaerobes included metronidazole and sulbactam/ampicillin, which demonstrated good activity against beta-lactamase producing Bacteroides spp. with the exception of Bacteroides distasonis. Resistance in non-beta lactamase producing anaerobes was similar to that seen with ampicillin. As expected, ampicillin resistance was common in the Bacteroides fragilis group where beta-lactamase production was frequent. In addition, beta-lactamase was detected in 33% of other Bacteroides spp. Ampicillin resistance was also seen in 5 to 15% of additional anaerobes that did not produce beta-lactamase. Clindamycin resistance occurred in 4 to 18% of the B. fragilis group. Clindamycin resistance was also seen in 7 to 8% of Clostridium spp. and anaerobic Gram-positive cocci. Resistance to cefoxitin was variable in the B. fragilis group with the highest levels of resistance occurring in the indole-negative subgroup. Resistance in other anaerobes was not commonly seen. PMID- 2591176 TI - In vitro activity of sulbactam in combination with various beta-lactam antibiotics. AB - Forty-three strains (beta-lactamase positive and negative) from the species of Haemophilus influenzae, Neisseria gonorrhoeae, Staphylococcus aureus, Escherichia coli, Serratia marcescens, Enterobacter cloacae, Acinetobacter baumanii, and Pseudomonas aeruginosa were studied for synergy between sulbactam and several beta-lactam antibiotics. Using a checkerboard method, synergy was observed with 10 to 55% of the beta-lactamase negative strains. Synergy was more frequent with the strains producing beta-lactamase. Using the killing curve method, synergy was also observed between sulbactam and beta-lactam antibiotics against some beta lactamase negative strains. In addition, the regrowth of a resistant subpopulation was prevented by sulbactam. PMID- 2591177 TI - Sulbactam/ampicillin in the treatment of pediatric infections. AB - Seventy eight pediatric patients (43 males, 35 females) aged 34 days to 17 years were treated with intravenous or intramuscular sulbactam/ampicillin 3 or 4 times daily for skeletal system infection (10 cases), systemic salmonellosis (2 cases), intrathoracic infection (12 cases), and soft tissue or miscellaneous infections (54 cases). The dose used to treat the majority of patients was 200 mg of ampicillin plus 100 mg of sulbactam per kg/day. The duration of treatment ranged from 8 to 23 days. Sulbactam/ampicillin alone was used in 68 patients. Ten patients were treated with an additional antibacterial agent. The overall cure rate was 98.7% for all 78 study patients. One patient with an abscess in the neck was shown to be infected with a strain of Escherichia coli resistant to sulbactam/ampicillin. Only one patient experienced a rash, but it did not necessitate discontinuation of therapy. This study shows that sulbactam/ampicillin is a safe and effective agent in the treatment of various pediatric infections. PMID- 2591178 TI - In vitro assessment of sulbactam plus cefoperazone in the treatment of bacteria isolated from cancer patients. AB - Cefoperazone is a broad-spectrum cephalosporin that has been used extensively to treat infections in cancer patients. A recent survey demonstrated only a 6% resistance to this drug among Gram-negative bacteria. The combination of cefoperazone plus sulbactam was studied in vitro against consecutive isolates causing bacteremia in cancer patients as well as those selected for resistance to cefoperazone. Both a fixed ratio of sulbactam/cefoperazone (2:1 w/w) and selected concentrations of sulbactam (2, 4, 8, and 16 micrograms/ml) were studied. Sulbactam was shown to increase the susceptibility of various unselected Gram negative bacilli; this effect increased with larger concentrations of sulbactam. The addition of sulbactam at optimum concentration levels made 29 of 65 cefoperazone-resistant Gram-negative bacilli susceptible. This effect was seen most markedly for Acinetobacter spp. PMID- 2591179 TI - Caries prevalence, Streptococcus mutans and sugar intake among 4-year-old urban children in Iceland. AB - Concern at the high prevalence of dental caries in Iceland prompted this survey of 158 preschool children in Reykjavik. On initial examination in 1987 45.8% of the children were caries-free and the prevalence of caries was a mean dmft 2.4 and a mean dmfs 3.3. A dietary questionnaire aimed at discovering the frequency of sugar consumption per week revealed a threshold value of 30 instances of sugar intake per week above which caries prevalence increased markedly. Some of this sugar is consumed in paediatric medicines, particularly antibiotics and anti asthmatics, which are widely used in Iceland. Caries prevalence (dmft) for children taking such medicines regularly was 3.0 compared with 2.1 for remaining children (P less than 0.05). Those children who took fluoride tablets regularly had less caries (mean dmft 1.1) than those who used fluoride tablets irregularly or not at all (mean dmft 2.8; P less than 0.001). Samples of saliva from the dorsum of the tongue were taken for determination of numbers of Streptococcus mutans and lactobacilli. High bacterial counts were strongly associated with caries. Only 5% of children with more than 5 x 10(5 S. mutans cfu per ml were caries free but 27% of subjects had 67% of the total amount of caries for the group and all of these would have been detected by the bacterial test. PMID- 2591180 TI - Influence of increased toothbrushing frequency on dental health in low, optimal, and high fluoride areas in Finland. AB - In our previous report we found that the dental health of Finnish 13-15-yr-old children had significantly improved from 1973 to 1982. The aim of this study was to assess whether the improved dental health was associated with frequency of toothbrushing and associated use of fluoride dentifrice. In both 1973 and 1982 some 360 children were scored for the DFS index. In each of three towns with 0.2 ppm, 1.0 ppm, and 2.5 ppm fluoride in the drinking water, samples of about 40 children were randomly picked from each age cohort of 13, 14, and 15 yr. The children were grouped into "infrequent", "daily", or "frequent" brushers. Overall, from 1973 to 1982 the proportion of "daily" and "frequent" brushers had increased from 56% to 75% (P less than 0.001). The overall DFST (T = total) and DFSA (A = approximal) scores had declined significantly in all brushing frequency groups. Looking at separate fluoride areas, the actual decline was found to have occurred in the low fluoride area where in 1982 the DFS scores were 50% or less of the 1973 scores (P less than 0.05). In the low fluoride area in 1973, no association was found between brushing frequency and DFS scores whereas in 1982, high brushing frequency was found to be associated with low DFS scores (P less than 0.05). The decrease in DFS scores was suggested at least partly to be associated with the increased frequency of brushing the teeth with fluoride dentifrice. PMID- 2591181 TI - Validity of CPITN's hierarchical scoring method for describing the prevalence of periodontal conditions. AB - CPITN has been a frequently used index in periodontal epidemiology during the last decade. It was originally designed to describe treatment needs in populations. For this purpose, it was decided to record only the worst periodontal condition around each index tooth. Such a recording procedure can be regarded as a hierarchical scoring method. Recently, CPITN has been used and recommended for describing the prevalence of periodontal conditions. For this purpose, the index should give a valid estimate of the true periodontal conditions of the index tooth, and not only a recording of the worst condition. The aim of the present study was to test whether the hierarchical assumption of CPITN concerning treatment needs was valid for describing the prevalence of periodontal conditions in a Scandinavian population. The study population comprised 3330 persons from a rural and an urban area in the county of Trondelag, Norway. The clinical recording was carried out so that it was possible to analyze the indicators both hierarchically and non-hierarchically. The results showed that nearly all the CPITN indicators scored hierarchically gave a correct estimate of the prevalence of bleeding in the population. CPITN codes 3 and 4 overestimated the prevalence of calculus. The degree of overestimation varied by age and tooth type. Most overestimation of calculus occurred on molar teeth with pockets 3.5-5.5 mm and for individuals 13-14 yr of age. There was almost no overestimation of calculus for those aged 65 yr and above.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591182 TI - Periodontal treatment needs in a population of Ljubljana, Yugoslavia. AB - 1692 citizens of Ljubljana in the age range from 15 to 65 yr participated in a survey to assess their periodontal treatment needs. Eighty-three of the participants (4.9%) were edentulous and excluded from the study. Of the 1609 dentate subjects only 2.4% were free of any signs of periodontal disease. According to the Community Periodontal Index of Treatment Needs, (CPITN), reversible gingivitis was present in 19.9% of the population, calculus and shallow pockets (4-5 mm) in 57.4%, and deep pockets (greater than or equal to 6 mm) in 20.3% of the examined participants. Bleeding on probing was the most common finding in a group of 15-yr-old subjects, calculus was most frequently found in 25- and 35-yr-old groups, and shallow and deep pockets in 45-, 55- and 65-yr-old adults. Complex treatment needs increased with age, reaching 42.9% in the 65-yr-old population. However, deep pocketing was in 60% limited to one sextant of the participants with complex treatment needs. PMID- 2591183 TI - Periodontal conditions in Hesse, Federal Republic of Germany, measured by CPITN. AB - The periodontal status and the need for treatment were investigated among 3140 inhabitants of the Federal German state of Hesse, using the CPITN index. The male and female subjects forming the case material were divided into 6 age categories (I up to 19 yr, II 20-24 yr, III 25-29 yr, IV 30-34 yr, V 35-44 yr, VI 45 yr or more). The dentitions of 1.3% of those examined were healthy from the periodontal aspects (CPITN 0). 3.3% of examined persons displayed an increased tendency towards bleeding on probing as the sole pathologic manifestation (CPITN 1); calculus and bleeding on probing (CPITN 2) were recorded in 35.5% of patients. Shallow pocketing (CPITN 3) was observed in 49.3, and deep pocketing (CPITN 4) in 10.6% of the examined subjects. There was a marked increase in scores 3 and 4 among patients from age group V. In addition, the posterior teeth were more susceptible to disease than those in the anterior segments, with slightly higher figures being recorded among female than among male individuals. 98.7% of the patients were in need of periodontal treatment. Application of the PTNS index yielded a treatment requirement of 6841.0 hours for the examined population. 2323 hours of this time were allocated to oral hygiene instruction, 4148 hours to scaling and 370 hours to surgical intervention. PMID- 2591184 TI - Visual and tactile observational error: comparative probing reliability with recession and cementoenamel junction measurements. AB - Probing error may arise from several sources, including visual observations and tactile detection of the cementoenamel junction (CEJ). This study examined two types of probe scale in relation to measurements of recession and CEJ from a flexible stent, and two types of probe design in addition, in relation to CEJ detection. 492 sites were studied in six patients with untreated periodontitis. Following stent construction, patients attended for measurement of recession and probing depth. This was repeated after 1 h, and then calculus was scaled in the vicinity of the CEJ. One week later, patients attended for CEJ measurements, which were similarly repeated. Measurements with an offset scale (between marks) were more reproducible in general, though no significant difference was detected between recession scores. The most reproducible detection of the CEJ was with a modified Cross calculus probe with an offset scale. A curious feature of the results was a bias affecting 9% of the recession measurements. It is possible that edematous enlargement of the gingiva occurred after the first measurement of probing depth, and was occasionally sufficient to alter the recession score. PMID- 2591185 TI - Dental status in a group of adult diabetic patients. AB - The aim of this study was to determine the prevalence of dental caries, DMFT score and treatment needs in a group of diabetic patients (n = 222), mean age 46.9 yr, and to compare them to those recorded in a control group (n = 189), mean age 43.9 yr, using WHO criteria. Relations between the type and duration of diabetes mellitus, diabetic complications (retinopathy and neuropathy), diabetic control, and the subjects' DMFT status were separately studied. The results obtained revealed no difference in the prevalence of caries between the group of diabetics and the control group. Neither was any difference found in the mean numbers of teeth with fillings, but the number of extracted teeth per subject was significantly higher in the group of diabetics (12.3) than in the control group (9.7) (P less than 0.01). Type I diabetics were found to have a significantly higher number of teeth with fillings (4.05 vs. 2.22) than the non-insulin dependent diabetics (P less than 0.001). Type II diabetics, however, had a significantly higher number of extracted teeth (14.1 vs. 10.4) (P less than 0.001). There was no difference in the caries experience regarding duration of diabetes, diabetic control, or diabetic complications. PMID- 2591186 TI - Relationship between habits and dental health among rural Tanzanian children. AB - The study was done in 1982/83 as an oral health baseline for a comprehensive health project involving primary school children in rural areas of Tanzania. A number of 399 standard two pupils with a mean age of 10.9 yr were dentally examined and interviewed using closed questions. Interexaminer reproducibility for caries was 99%, inter-interviewer reliabilities for population correspondence were between 81% and 100%. DMFS + defs was 1.1 for the 92% brushing their teeth daily and 1.9 for children brushing once a week or less. The amount of plaque, calculus, and gingivitis showed no relation to brushing, if it was performed more than once a week. The effect of using chewing sticks or plastic toothbrushes was identical. Children eating cakes, biscuits and/or sweets at least three times a day seemed to have more caries than the rest, DMFS + defs being 1.5 and 1.1, respectively. Consumption of sugar cane did not show any relation to the caries amount. In one of five districts traditional removal of primary tooth germs had caused a mean loss (or deformity) of 1.0 permanent tooth, thereby being the most injurious dental condition. The study confirms the need of educational interventions. It does not indicate any justification for prompting children in general to brush more than once a day or restricting sweet snacks to less than once a day. PMID- 2591187 TI - Oral lichen planus among 4277 patients from Gizan, Saudi Arabia. AB - This paper reports on the prevalence of oral lichen planus among 4277 Saudi patients, aged 18-73 yr, seen in the dental department of King Fahd Central Hospital, Gizan, Saudi Arabia, between 1982 and 1987, 63% of the patients were males. Oral mucosal lesions consistent with lichen planus were identified both clinically and histologically in 72 patients (40 males and 32 females). The average age of the affected group was 49 yr. No correlation was evident between lichen planus and tobacco habits in this study, nor was there any association with diabetes or hypertension. The average period of follow-up was 3.2 yr, during which four cases developed malignant transformation of the oral lesions. The prevalence of oral lichen planus in this study was 1.7%, which is higher than the prevalence figures reported earlier for the population of Saudi Arabia. PMID- 2591188 TI - Periodontal status in a Hutterite population. AB - The periodontal status of a population of 117 adult Hutterites living in Saskatchewan, Canada, was assessed. Despite poor oral hygiene levels, and inadequate dental knowledge, the presence of periodontitis was low. The findings are in accordance with data obtained recently from other selected populations. PMID- 2591189 TI - Adipose tissue in the mammalian heart and pericardium: structure, foetal development and biochemical properties. AB - 1. The occurrence and relative abundance of adipose tissue around the heart and in the pericardium of wild and domesticated mammals are reviewed and some new data reported. 2. For macaque monkeys and a wide range of other adult mammals, the mean volume of epicardial adipocytes is constant at about half the average of that of other depots, although the relative mass of this depot is unrelated to the abundance of adipose tissue in the rest of the body. 3. In young adult guinea pigs, the maximum rate of fatty acid synthesis is significantly higher in epicardial adipose tissue than that in the pericardial, perirenal and popliteal depots. 4. The rate of fatty acid release by epicardial adipose tissue is approximately twice that of the pericardial and perirenal depots. 5. The protein contents of guinea-pig epicardial and pericardial adipose tissue are similar, and are significantly higher than those of the perirenal and popliteal adipose tissue and there are no site-specific differences in the abundance of mitochondria. 6. In adult Macaca monkeys, the capacity of the epicardial adipose tissue for glucose utilization is about half that of the intra-abdominal depots. 7. The principal difference between epicardial adipose tissue and that elsewhere in the body is its greater capacity for fatty acid release. 8. It is suggested that cardiac adipose tissue may act as a local energy supply for adjacent myocardium and/or as a buffer against toxic levels of free fatty acids. PMID- 2591190 TI - Independent characterization of thymidine transport and subsequent metabolism in Hymenolepis diminuta--I. Comparison of short- and long-term transport kinetics. AB - 1. Initial transport kinetics of thymidine in the rat tapeworm, Hymenolepis diminuta have been characterized independently of subsequent metabolic activity, using short term (5s) incubation times. 2. Thymidine uptake by 10 day old worms using long-term (2 min) incubation times underrepresents actual transport capabilities by allowing subsequent phosphorylation to act as a rate limiting step in the coupled transport-metabolism pathway. 3. Apparent Kt values for 6 and 10 day old H. diminuta thymidine transport at 5s incubation times (0.073 nM and 0.091 mM) are close in value. Distinctions previously observed at 2 min incubation times may actually represent metabolic (and not transport) differences. PMID- 2591191 TI - A comparative study of synthetic carnosine analogs as antioxidants. AB - 1. The antioxidative activity of carnosine and 16 related compounds, both synthetic and natural, was determined. 2. The antioxidative effect was estimated by the ability of the dipeptides to prevent MDA accumulation in the course of LPO induced in rabbit sarcoplasmic reticulum membranes by the Fe2+ ascorbate system. 3. It was found that the antioxidative effect comparable to that of carnosine was exerted by water-soluble (cyclo-L-histidyl-L-proline) and alcohol-soluble (cyclo L-histidyl-L-phenilalanine) dipeptides as well as by the histidine-free cyclodipeptides (cyclo-L-tyrosyl-L-proline). 4. However, in contrast to its synthetic analogs, carnosine not only inhibited the LPO, but also diminished the level of products accumulated during membrane lipid peroxidation. PMID- 2591192 TI - Trypanocidal CoQ analogues: their effect on other mitochondrial systems. AB - 1. A comparative study of compounds which inhibit the respiration of the infective form of the protozoan parasite Trypanosoma brucei brucei, such as salicylhydroxamic acid, other substituted benzhydroxamic acid, esters of 2,3- and 3,4-dihydroxybenzoic acid and structurally related compounds, showed that they have a remarkable degree of selectivity for the trypanosome as compared to rat liver mitochondria even though they are putative CoQ analogues and both respiratory systems are dependent on CoQ. 2. The minimal inhibition of mammalian mitochondrial function could not be assigned to inhibition of ubiquinone function in these mitochondria. 3. CoQ-reducing mitochondrial dehydrogenases from rat liver, trypanosomes and skunk cabbage (Symplocarpus foetidus) were insensitive to these inhibitors. 4. The alternative oxidase of skunk cabbage mitochondria was sensitive to a spectrum of trypanosome respiration inhibitors suggesting a similarity to the oxidase of the trypanosome although differing degrees of sensitivity and differing responses to alterations in the molecular structure of the inhibitors indicate that the milieu of the active sites are dissimilar. PMID- 2591193 TI - Selenium-independent glutathione peroxidase activity associated with glutathione S-transferase from the housefly, Musca domestica. AB - 1. A glutathione S-transferase having Se-independent glutathione peroxidase activity was isolated from 100,000 g supernatant from housefly homogenate. 2. The specific activity of the partially purified Se-independent glutathione peroxidase was 1776 nmol NADPH oxidized/min/mg protein, representing an 87-fold purification. 3. The Mr of this enzyme was estimated to be 37,000 and 26,000 by gel filtration chromatography and gel electrophoresis, respectively. 4. Selenium dependent glutathione peroxidase activity could not be detected in this same supernatant. 5. Se-independent glutathione peroxidase activity should be considered in future studies of the insect antioxidant defense system. PMID- 2591195 TI - Lipid synthesis and lipoprotein secretion by chick liver cells in culture: influence of growth hormone and insulin-like growth factor-I. AB - 1. Chick liver cells were incubated in unsupplemented medium (control), or medium supplanted with either 1 microgram/ml pituitary derived chicken growth hormone (GH), 50 ng/ml recombinant human insulin like growth factor-I (IGF-I), or 1 microgram growth hormone/ml and 50 ng insulin like growth factor-I/ml (GH + IGF I). 2. GH supplementation stimulated acetate incorporation into liver cell lipid. Low density lipoprotein (LDL) lipid secretion was increased quantitatively by GH. 3. Cells incubated with IGF-I incorporated more acetate into lipid and secreted more lipid as VLDL and HDL than controls. 4. A metabolic antagonism between GH and IGF-I was evident with respect to lipogenesis. 5. Neither GH nor IGF-I altered, quantitatively, cell protein synthesis or apoprotein secretion. PMID- 2591194 TI - On the acid phosphatase isoenzymes existing in American Leishmania promastigotes. AB - 1. Two partially purified acid phosphatase activities present in American Leishmania promastigote homogenates were characterized by biochemical methods. 2. One isoenzyme acts preferentially on p-nitrophenyl phosphate, is strongly inhibited by 30 mM alloxan, citrate, maleate, malonate and succinate, and strongly stimulated by 3 mM spermine. Its pI is 4.8. 3. The other isoenzyme acts preferentially on beta-glycerophosphate and is resistant to 30 mM alloxan, citrate, maleate, malonate and succinate and also to 3 mM spermine. Its pI is 5.7. 4. Both acid phosphatase isoenzymes have an optimum pH of 5.2, are tartrate sensitive and strongly membrane-bound, as shown by differential centrifugation and density gradient equilibration. 5. Both isoenzymes were separated by using homogenates prepared in 2% Triton X-100, differential centrifugation, Sepharose 4B/CL-4B gel filtration, ion exchange chromatography and electrofocusing. After this procedure, they were still contaminated with several different proteins. 6. Purification was around 150-fold, with a 32% yield. 7. When these acid phosphatase activities were measured in total homogenates from 12 different Leishmania isolates, p-nitrophenyl phosphatase specific activity values were quite close; beta-glycerophosphatase-specific activity had around a 2-fold variation. 8. This variation was independent from taxonomic classification or infectivity of susceptible hosts. PMID- 2591196 TI - Comparison of xanthine: NAD+ oxidoreductase from liver of toad Bufo viridis and other vertebrates. AB - 1. Xanthine oxidoreductase was isolated from toad Bufo viridis (a mainly ureotelic amphibian species) and partially purified. The enzyme occurred as a stable xanthine: NAD+ oxidoreductase (EC 1.1.1.204), unconvertible to the oxidase form. 2. Some properties of the enzyme resembled those of xanthine oxidoreductase from an ammonotelic fish, Cyprinus carpio, and the ureotelic rat, but in other aspects it was similar to this enzyme from an uricotelic snake, Natrix natrix. 3. Inhibition of the toad enzyme by NADH at high non-physiological concentrations rules out a modulation of its oxypurine-hydroxylating activity by in vivo changes in the NADH/NAD+ ratio. Therefore, toad xanthine oxidoreductase plays no regulatory role in the purine nucleotide metabolism. PMID- 2591197 TI - Polyunsaturated fatty acid metabolism in fish cells: differential metabolism of (n-3) and (n-6) series acids by cultured cells originating from a freshwater teleost fish and from a marine teleost fish. AB - 1. The incorporation and metabolism of (n-3) and (n-6) polyunsaturated fatty acids (PUFA) supplemented to growing cultures were studied in rainbow trout (RTG 2) and turbot (TF) cell lines. 2. A fatty acid concentration of 20 microM considerably altered the fatty acid composition of the cells without affecting lipid class composition or the appearance of cytoplasmic lipid droplets. 3. Both cell lines exhibited considerable delta 6 desaturase activities. 4. Whereas delta 5 desaturase activity was expressed in RTG-2 cells, delta 4 desaturase activity was absent and, conversely, delta 4 desaturase activity was expressed in TF cells, but there was an apparent deficiency in the C18 to C20 elongase multi enzyme complex. 5. The delta 6 desaturase activity in both cell lines showed little preference between 18:2(n-6) and 18:3(n-3) but the delta 5 desaturase activity of RTG-2 cells and the delta 4 desaturase activity of TF cells showed a preference for (n-3)PUFA. 6. Two fish oil concentrates were assessed for their ability to generate fatty acid compositions in the cell lines more closely resembling those of intact fish tissues. PMID- 2591199 TI - The cuticular proteins from free-living and parasitic stages of Haemonchus contortus--I. Isolation and partial characterization. AB - 1. Cuticles were isolated from the adult males, adult females, the second molt (2M) sheath from the infective larvae (L3(2M)), and the parasitic third stage (L3) of the sheep parasite Haemonchus contortus by a combination of mechanical disruption and detergent treatment. 2. The 2ME soluble cuticular proteins from adult males contained 4 or 5 major protein bands with molecular weights ranging from 100 to 56 kD with the most prominent band at 56 kD. The cuticular proteins from adult females were similar to the male. 3. Cuticular proteins from the larval stages, 2M cuticle, and L3 cuticle, differed from the adults and from each other. The most prominent protein bands were observed with molecular weights on 78 and 39 kD for the L3 cuticle and 100, 91 and 46 kD for the 2M cuticle. The 2ME soluble cuticular proteins from all developmental stages were at least partially digested by bacterial collagenase. 4. The amino acid composition of cuticular proteins was similar for the L3 and 2M, but adults had lesser amounts of glycine and greater amounts of basic amino acids than the larval stages. The amount of the isolated cuticle solubilized by the 2ME treatment was greatest in adults (80%) compared to the L3 (64%) and the 2M (22%). 5. These results support a hypothesis that there are quantitative and qualitative stage specific differences in the cuticular proteins of H. contortus. PMID- 2591198 TI - Glycoproteins in Rathke's gland secretions of loggerhead (Caretta caretta) and Kemp's ridley (Lepidochelys kempi) sea turtles. AB - 1. The Rathke's gland secretions of loggerhead (Caretta caretta) and Kemp's ridley (Lepidochelys kempi) sea turtles contain 20 and 10 mg of protein/ml, respectively. The proteins of each species were separated by gel filtration into two major fractions, one (35%) in the excluded volume, and one (50%) with a molecular mass of approximately 55 kDA. 2. The 55 kDa fraction from each species' secretions exhibits a single band on SDS-PAGE (Mr approximately equal to 55,000) and a single amino-terminal sequence. 3. The amino acid compositions of the two 55 kDa proteins are similar, and the first 15 residues of their amino terminus are identical. Both proteins contain glucosamine. 4. Analyses of the amino acid and amino sugar composition of the high molecular weight fractions from the two turtle species also indicate similarities; there are distinct differences between them and their 55 kDa proteins. PMID- 2591201 TI - Purification and characterization of Cu,Zn-superoxide dismutase from common carp liver. AB - 1. Common carp (Cyprinus carpio L.) liver Cu,Zn-superoxide dismutase (Cu,Zn-SOD) was purified and characterized. 2. Its molecular weight, isoelectric point, electrophoretic mobility, amino acid pattern and some other characteristics were determined. PMID- 2591200 TI - Studies on the structure of lecithin:cholesterol acyltransferase (LACT)- comparisons of the active site region and secondary structure of the human and the porcine enzymes. AB - 1. Chemical modification of essential serine, histidine and cysteine residues of porcine LCAT were accompanied by loss of enzymatic activity. 2. Modification of cysteine with DTNB inactivated the enzyme which could not be reactivated by KCN suggesting direct involvement of the cysteine residue(s) in catalysis. 3. About half of the primary structure of the porcine enzyme was determined. 4. Respective regions of the human and porcine LCAT are highly homologous; especially, the amino-terminus and the region surrounding the DFP-labeled serine residues. 5. The observed primary structure differences represent amino acid substitutions that are projected to induce significant changes in secondary structure. PMID- 2591202 TI - Tissue difference in cellular localization of thiamine phosphate esters. AB - 1. Thiamine phosphate levels were determined in the soluble and particulate fractions of various rat tissues. 2. There was marked tissue difference in the cellular localization of thiamine phosphates. 3. Brain thiamine triphosphate was localized only in the particulate fraction, whereas skeletal muscle thiamine triphosphate was in the soluble fraction as a protein-unbound form. PMID- 2591203 TI - Mammary extraction of plasma triglycerides in the cow during lactogenesis. AB - 1. In control cows, extraction of triglycerides from the circulation by the mammary gland increased abruptly and markedly, and the concentration of triglycerides in arterial plasma fell, on the day of parturition. 2. In cows that had fluid regularly removed from the mammary glands before parturition, these changes occurred at varying times from more than 4 days before parturition in an animal that secreted triglyceride copiously to 24 hr before parturition in an animal that secreted little triglyceride pre-partum. 3. In all animals, the time when triglyceride extraction increased was close to the time when K+ concentration in the mammary secretion became maximal. PMID- 2591204 TI - Subunit structure and higher order assembly of the hemocyanins of the Melongenidae family: Melongena corona (Gmelin), Busycon canaliculatum (Linne), B. carica (Gmelin), B. contrarium (Conrad), and B. spiratum (Lamarck). AB - 1. The hemocyanins of the Melongenidae family of marine gastropods: Melongena corona, Busycon canaliculatum, B. carica, B. contrarium, and B. spiratum exist in solution as multi-decameric aggregates characterized by sedimentation coefficients of approximately 105 S, 130 S, 150 S, 170 S, and higher values, corresponding to di-, tri-, tetra-, penta-, and larger multi-decameric particles. 2. The hemocyanins of B. contrarium and B. carica seem to form the largest decameric aggregates with the tri- to penta-decamers respresenting the major constitutents. Scanning transmission electron microscopy (STEM), both of unstained, freeze-dried and negatively-stained specimens, shows the presence of discrete aggregates consisting of up to ten decameric units. 3. The particle masses as determined by STEM mass measurements for individual molecules gave integral multiples of from 4.2 x 10(6) to 4.4 x 10(6) daltons ranging from about 8.2 x 10(6) daltons for the typical di-decamer of B. canaliculatum hemocyanin to as high as about 39 x 10(6) and 43 x 10(6) for the nano-and deca-decamers of B. contrarium hemocyanin. 4. The appearance of the higher multi-decamers in both negatively-stained and freeze-dried specimens suggest that they are formed by the addition of decameric units to a single di-decameric unit "tail-wise" in both directions. The higher aggregates formed seem to terminate with a closed head or collar at both ends of the assembly. PMID- 2591205 TI - Supercomputers and biological sequence comparison algorithms. AB - Comparison of biological (DNA or protein) sequences provides insight into molecular structure, function, and homology and is increasingly important as the available databases become larger and more numerous. One method of increasing the speed of the calculations is to perform them in parallel. We present the results of initial investigations using two dynamic programming algorithms on the Intel iPSC hypercube and the Connection Machine as well as an inexpensive, heuristically-based algorithm on the Encore Multimax. PMID- 2591206 TI - Extended relational operators for statistical data manipulations in medical databases. AB - Conventional relational database management systems fail to address three features of statistical data management in a biomedical/clinical database, namely, that (1) statistical and medical data (SMD) require a great deal of space and need to be stored in a reduced form with minimal duplication; indeed, SMD have many derived/calculated and summary statistics that make the number of attributes in a relation (i.e., a set of records) grow rapidly and dynamically; (2) most SMD have hierarchical structures that are difficult to manage using the relational data model since SMD are stored in separate relations for duplication and space considerations; and (3) the management of SMD is made easier if it is possible to reorganize relations or group data, a capability lacking in conventional relational database management systems. In this paper, we (1) introduce five extended relational operators, (lattice) NEST, (lattice) UNNEST, MERGE, SPREAD, and GEN, to reorganize relations; (2) integrate the extended operators with conventional relational algebra and introduce the concept of the lattice relational model; and (3) give applications of the extended relational operators and the lattice relational model in solving the problems of statistical data manipulation in medical databases. PMID- 2591207 TI - A method for comparing semi-parametric models with parametric models in competing risks analysis. AB - In survival analysis, Cox's regression model is often used to assess the effect of covariates on the time of failure. This semi-parametric model has been extended to the situation where more than one cause of failure is of interest. In this paper, two semi-parametric models for the analysis of competing risks with covariates in the presence of independent random censoring are considered. Particular attention is devoted to the comparison between the two models. A method using a measure derived from the generalized variance is proposed. This method is illustrated with an example in a cancer clinical trial. A FORTRAN program for the computer implementation of the method is also discussed. PMID- 2591209 TI - Community nurse profile. A welcome visitor. PMID- 2591208 TI - Expected pressure-volume heterogeneity within the lung. AB - Using a model of the lung providing for pressure-volume (P-V) heterogeneity, we reproduced straight (allowing for some concavity or convexity) alveolar plateaus in the nitrogen washout curve with a slope identical to an experimentally measured one (1.2% N2/liter). In a two-unit lung, with one unit of high volume (H) at total lung capacity (TLC) and another of low volume (L) at TLC, three variables could be adjusted to produce the desired alveolar plateaus: the ratio of TLCL/TLCH; the ratio of functional residual capacity, FRCL/FRCH; and the ratio of the steepness constants of their sigmoid P-V curve, KL/KH. We searched for all possible combinations of the three variables that yielded the desired alveolar plateau. For any TLCL/TLCH ratio, there were two single-value solutions for the FRCL/FRCH ratio; thus, the family of solutions was represented by two surfaces in three-dimensional space. We extended the study to a smaller alveolar slope (0.6% N2/liter), assuming that the total slope (1.2% N2/liter) was partially caused by diffusion-convection interaction. We also studied a three-compartment lung as indicative of a multicompartmental lung. The results are discussed in relation to experimentally confirmed P-V heterogeneity. Granting our basic assumptions of P-V heterogeneity, the real physical lung characteristics may be a subsection of the range of theoretical solutions described herein. PMID- 2591211 TI - Westward ho! Off-shore care. PMID- 2591210 TI - Community nurse profile. Keeping in touch. PMID- 2591212 TI - Westward ho! Navy visiting. PMID- 2591213 TI - Westward ho! Cornish care. PMID- 2591214 TI - The cold that kills. PMID- 2591216 TI - Treating malodorous wounds. PMID- 2591215 TI - Prescribing change. PMID- 2591217 TI - Infant care. Cot death. PMID- 2591218 TI - Infant care. When to wean. PMID- 2591219 TI - Atropine pharmacokinetics are affected by moderate hemorrhage and hypothyroidism. AB - Atropine is used both to treat a variety of clinical disorders and as an antidote to cholinesterase poisoning. While various conditions affect the physiologic responses to atropine, little is known of the pharmacokinetics of this drug except under resting conditions. Pharmacokinetic studies were performed in mongrel dogs under two experimental conditions, moderate hemorrhage and hypothyroidism, to determine whether im absorption and elimination of atropine (0.05 mg/kg body weight) were affected by changes in hemodynamic or metabolic status. Using a randomized, crossover experimental design, it was found that during hypovolemia the mean volume of distribution was reduced by 22% (2.50 +/- 0.62 vs. 3.21 +/- 0.63 L/kg), with no changes in peak serum level, total atropine availability, elimination half-life, or whole-body clearance. Hypothyroidism was associated with a significant increase in peak serum atropine concentration (26.4 +/- 3.9 vs. 20.6 +/- 4.9 ng/ml) and drug bioavailability (48.5 +/- 8.8 vs. 30.0 +/- 10.7 ng/ml.h), while the clearance was reduced by 39% (426 +/- 34 vs. 696 +/- 187 ng/ml.min). These results suggest that atropine kinetics are not altered appreciably during moderate hemorrhage. In hypothyroidism, alterations in atropine pharmacokinetics may warrant modification of drug dose and frequency of administration. PMID- 2591220 TI - High dose epinephrine in refractory pediatric cardiac arrest. AB - Cardiac arrest has a poor prognosis, regardless of age group. Children who fail to respond to two standard doses of epinephrine (0.01 mg/kg) rarely survive to hospital discharge, and most die without the return of spontaneous circulation (ROSC). We treated seven consecutive children in cardiac arrest with high dose epinephrine (0.2 mg/kg) after failure to respond to two standard doses. Six had prompt and sustained ROSC. By comparison, in the previous 20 consecutive pediatric patients with cardiac arrest in which there was no response to two standard doses of epinephrine, none had ROSC. Previous animal data as well as anecdotal human experience suggest that the standard epinephrine dose (0.01 mg/kg) may be much too low. PMID- 2591221 TI - Comparison of prehospital conventional and simultaneous compression-ventilation cardiopulmonary resuscitation. AB - Nine hundred ninety-four patients were enrolled in a field trial in which ambulance crews were randomly assigned to use simultaneous compression ventilation (SC-V) CPR or conventional CPR procedures in the prehospital setting. Survival to hospital admission and to discharge was superior in the conventional CPR group vs. the experimental group (p less than .01). In a subset of adult cases whose causes of arrest were nontraumatic, survivor rates still favored the conventional CPR group: 33.5% of 337 vs. 22.5% of 365 (p less than .001). In limited cases where cardiac arrest was due to other heart disease, was vascular in origin or secondary to other natural diseases or from hypertensive cardiovascular disease, or when ECG on arrival was an agonal rhythm, survival was better (but not statistically significantly) in the experimental group. There were no statistically significant differences in the Glasgow coma scores between surviving patients in either group at 24 h post-hospital admission or discharge. It is concluded that survival in the SC-V CPR group was lower, likely reflecting a deleterious effect of the experimental technique of resuscitation. Also noted was that 14% of the control patients and 6% of the experimental patients survived with manual CPR alone. PMID- 2591222 TI - Hemodynamic responses to amiodarone in critically ill patients receiving catecholamine infusions. AB - The hemodynamic response after an iv loading dose of amiodarone for resistant supraventricular tachyarrhythmias was studied in ten critically ill patients receiving a catecholamine infusion for shock. A loading dose of amiodarone, 3.7 to 5.0 mg/kg, was infused over 2 h while the catecholamine infusion dose requirements were monitored. There was a significant decrease in heart rate (mean 16%, p less than .01), and an increase in stroke volume index (mean 29%, p less than .01) and left ventricular stroke work index (mean 34%, p less than .01). Cardiac index, oxygen availability index, and mean arterial pressure were not changed significantly. The reported adrenoreceptor antagonism of amiodarone did not change catecholamine dose requirements in this study. In nine of ten patients, sinus rhythm was achieved and maintained. The loading dose of amiodarone had no significant acute effect on plasma digoxin concentrations. Despite good arrhythmia control, mortality was high. PMID- 2591223 TI - Cell metabolism in patients undergoing major valvular heart surgery: relationship with intra and postoperative hemodynamics, oxygen transport, and oxygen utilization patterns. AB - The relationships between cell metabolism and both hemodynamics and oxygen transport/utilization (VO2/DO2) pattern were evaluated intra and postoperatively in eight patients undergoing major valvular heart surgery with the aid of moderately hypothermic cardiopulmonary bypass (CPB). Quadriceps femoris specimens were obtained by the needle biopsy technique for muscle ATP, ADP, AMP, phosphocreatine (PCr), creatine and lactate determination at anesthesia induction, after CPB, as well as in the ICU 18 h after surgery. Moreover, hemodynamic variables, oxygen transport and utilization indices, and plasma lactate were measured at the same intervals and throughout the CPB period. After CPB, muscle ATP and PCr contents were reduced (p less than .05) as compared to those of both pre-CPB patients and healthy control subjects; muscle and plasma lactate levels were increased (p less than .05). Mean VO2 and DO2 values measured during CPB significantly decreased (p less than .05), but VO2 reduction was proportionally greater than that of DO2 (-62% vs. -41%). No correlation was found between VO2 and DO2 at that time, but a significant relationship (p less than .05) was found at the end of CPB. A further decrease in muscle ATP and PCr levels was measured in the ICU, as muscle and plasma lactate levels were still elevated. At that time, VO2 and DO2 were not significantly different from pre-CPB values, but were significantly (p less than .05) correlated with each other.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591224 TI - Myocardial response to alpha-agonist (phenylephrine) in relation to age. AB - We studied the inotropic effect of the alpha-agonist phenylephrine on human and rat myocardium in relation to age. Strips of human atrial myocardium, discarded during cardiac surgery, were obtained from pediatric (2 to 18 months) and adult (40 to 60 yr) patients, and their electrically driven contractions were studied. The inotropic response of pediatric myocardium to phenylephrine was five times larger than that of the adult myocardium (p less than .05). The beta-agonist, isoproterenol, was also administered to the same myocardial specimens, and the average pediatric myocardial response was three times larger than that of the adult myocardium (p less than .05). Strips of right ventricular myocardium were obtained from four age groups of rats: 14 days, 3 months, 6 months, and 18 months, and exposed to phenylephrine. We demonstrated two age-related phenomena: a) a biphasic response with an early short negative inotropic effect preceding a sustained positive inotropic effect was registered in most of the rats aged 3 months and older, but in none of the youngest age group. b) A high mean positive inotropic response (211% of basal response) was generated in the youngest age group, whereas the oldest age group of rats showed only a slight response (8% of basal response, p less than .05). We conclude that loss of myocardial responsiveness to alpha and beta-agonist with increasing age is a prominent feature. The pattern of the ventricular responsiveness to phenylephrine also changes during aging as it turns from monophasic to biphasic. PMID- 2591225 TI - Electron microscopic evaluation of bacterial adherence to polyvinyl chloride endotracheal tubes used in neonates. AB - Studies in adults suggest a possible association between pulmonary nosocomial infection and bacterial adherence to endotracheal tubes (ETT). Some strains of coagulase-negative Staphylococcus produce a mucoid extracellular material known as slime or glycocalyx that helps bacteria adhere to the surface of biomaterials. We examined by scanning and transmission electron microscope the surface of 29 polyvinyl ETT removed from neonatal patients, and ten unused ETT. Multiple surface irregularities were found in the unused tubes. These irregularities were most prominent in the tip and around the side hole. Amorphous material containing slime-producing bacteria was found on 29 ETT removed from patients. Tubes in place for longer times had greater areas of surface covered; the amorphous material was more concentrated in the areas where surface irregularities were most prominent. No clinical correlation with pulmonary nosocomial infection was established. PMID- 2591226 TI - Potential protective effects of furosemide against early renal injury in liver transplant patients receiving cyclosporine-A. PMID- 2591227 TI - Reliability of right atrial pressure monitoring to assess left ventricular preload in critically ill septic patients. AB - Right atrial pressure (RAP) can be used as a guide to fluid therapy in critical care settings. RAP and pulmonary capillary wedge pressure (WP) were measured in 27 septic patients without cardiac disease and on mechanical ventilation. An r of .61 was obtained with a regression line defined by the equation WP = 7.38 + (0.53 x RAP) +/- 3.15. However, a large SD of data points can invalidate the clinical usefulness of this equation. The reliability of various RAP interval values in predicting optimal WP was then studied in these patients. We concluded that RAP values less than or equal to 5 mm Hg were highly specific (97%) in predicting low or normal WP (less than or equal to 12 mm Hg). PMID- 2591228 TI - Unrelenting hypoxemia and fatal myocardial infarction resulting from paradoxical embolization through an atrial septal defect. PMID- 2591230 TI - Peripheral tissue perfusion. PMID- 2591229 TI - Informed consent: resistance and reappraisal. PMID- 2591231 TI - Selective decontamination of the digestive tract in Kuwait. PMID- 2591232 TI - A simple technique to determine intra-abdominal pressure. PMID- 2591233 TI - Effect of injection site on circulation times during cardiac arrest. PMID- 2591235 TI - Methodologic assessment of outcome. PMID- 2591236 TI - APACHE III study design: analytic plan for evaluation of severity and outcome. PMID- 2591237 TI - Peer review, publication policy, and APACHE. PMID- 2591234 TI - Transitory phrenic nerve palsy after subclavian vein puncture. PMID- 2591238 TI - Reassessing critical care: illness, outcome, and cost. PMID- 2591239 TI - APACHE III study design: analytic plan for evaluation of severity and outcome in intensive care unit patients. Introduction. PMID- 2591240 TI - APACHE III study design: analytic plan for evaluation of severity and outcome in intensive care unit patients. Study design--data collection. PMID- 2591241 TI - APACHE III study design: analytic plan for evaluation of severity and outcome in intensive care unit patients. Statistical methods. PMID- 2591242 TI - APACHE III study design: analytic plan for evaluation of severity and outcome in intensive care unit patients. Development of APACHE III. PMID- 2591244 TI - APACHE III study design: analytic plan for evaluation of severity and outcome in intensive care unit patients. Analysis: quality of care. PMID- 2591243 TI - APACHE III study design: analytic plan for evaluation of severity and outcome in intensive care unit patients. Individual patient decisions. PMID- 2591245 TI - APACHE III study design: analytic plan for evaluation of severity and outcome in intensive care unit patients. Analysis of process. PMID- 2591246 TI - APACHE III study design: analytic plan for evaluation of severity and outcome in intensive care unit patients. Efficiency and nurse staff. PMID- 2591247 TI - APACHE III study design: analytic plan for evaluation of severity and outcome in intensive care unit patients. Implications. PMID- 2591248 TI - Evaluation of attempted suicides: a comparative study of staff in a general hospital and consulting staff in a psychiatric hospital. AB - The study group consisted of medical staff (n = 53) working in the emergency department of the general hospital in Helsinki, Finland, which treats almost all self-poisonings in the area. Some of the staff in the Department of Psychiatry formed the comparison group (n = 30). The study method was an interview based on real cases of attempted suicide. The previous four cases taken for consultation by the Department of Psychiatry were chosen. The interview was based on the consultation form used in the Department of Psychiatry of Helsinki University Central Hospital. The answers of the original consultant were compared to the results from the two groups. The study group could well assess the somatic severity (lethality) of all suicide attempts, whereas the comparison group often assessed them to be more severe than the original consultant. There were no noteworthy differences between the groups concerning the assessment of the psychiatric severity (the intent to die) of the suicide attempts and the necessary after-care. The comparison group considered all suicide attempts as understandable acts, whereas there was a distribution in the results from the study group. In general, on the basis of the results, it can be said that the staff in the psychiatric hospital were significantly more cautious in their assessments than the staff at the general hospital. PMID- 2591249 TI - Suicide across the adult life-span: an archival study. AB - This archival study, concerning the demographic variable of age, involved the assessment of 8 identified classifications (clusters) as possible predictors of suicide notes and, by implication, suicide. The possible predictors, derived from the theoretical work of 10 suicidologists, were as follows: unbearable psychological pain, interpersonal relations, rejection-aggression, inability to adjust, indirect expressions, identification-egression, ego, and cognitive constriction. Independent judges noted the incidence of contents corresponding to 36 specific protocol sentences, constituting the 8 clusters, in 60 suicide notes- 20 notes written by individuals in Young, Middle, and Late Adulthood. An analysis was able to discriminate the age groups on a number of clusters, notably in regard to Young Adults, although considerable commonalities were noted across the adult life span. The results indicate that a life-span perspective is essential when one is constructing a model to interpret suicide of adults. PMID- 2591250 TI - A cross-cultural comparison of ideal and undesirable qualities of crisis line workers. AB - Telephone crisis line workers in two different crisis centers (Los Angeles, USA, and Ljubljana, Yugoslavia; LA and LJ) self-assessed the most important ideal and undesirable personality traits for their work. Both LA and LJ counselors rated the most important traits as: motivated for the work and being a good listener. LA counselors rated themselves as possessing the majority of the required positive traits, while the LJ counselors thought themselves lacking in several significant qualities. In their listing of undesirable traits, the LJ workers again tended to be more critical of themselves than the LA workers but with fewer differences than on the desirable traits. The source of the differences may lie between the use of volunteers in LA and professional and semi-professional counselors in LJ. The ratings of a sample of US crisis center directors on both desirable and undesirable traits tended to parallel those of the LJ counselors more closely than those of the LA workers. Center directors were also critical of their own counselors on a number of the listed traits. PMID- 2591251 TI - Roulette of the road: a new kind of suicide attempt? A preliminary report. AB - The author reports on children aged 7-14 who throw an object onto the highway shortly before a car comes and run to fetch it in front of the approaching automobile. He discusses the problems linked with that roulette-style play with death. PMID- 2591252 TI - Public health education against suicide: a new strategy for prevention. AB - The authors propose education against suicide, rather than the present practice of dissemination of information about suicide. It may well be that information with such a focus would prove to be more of a deterrent to suicide than information with the current focus. PMID- 2591253 TI - Effect of hyperthermia on lymphocyte plasma membrane. 3 electrolyte spin labels permeability. AB - The effect of elevated temperatures on the transport of electrolyte spin labels anionic c-TEMPIR and cationic TEMPO-choline character across the porcine lymphocyte plasma membrane was investigated. Breaks in the Arrhenius plot for permeability of both spin-labels occurred at 42 to 43 degrees C. TEMPO-choline and c-TEMPIR transport are probably critical targets in hyperthermic cell killing. PMID- 2591254 TI - Seasonal ultrastructural changes in the pineal gland of the migratory Canada goose. AB - Ultrastructural changes in the pineal gland were studied in relation to migration, breeding and moult. Sizes of pinealocytes and that of their nuclei were greatest in the Spring premigratory and postmigratory, and moult phases. The ratio of nuclear size to cell size was greatest for the breeding phase and lowest for the Fall premigratory and postmigratory phases. The Golgi complex was most prominent during premigratory and breeding phases. Mitochondria which were numerous in all phases except during moult, were markedly enlarged during breeding and Fall premigratory phases. Dense-core vesicles were predominant in Spring postmigratory and moult phases. In glial cells, lipoid inclusions were abundant in Spring premigratory and postmigratory, and breeding phases. Glycogen granules were abundant in Spring postmigratory, breeding and moult phases. Large vacuoles were present in Fall premigratory phase. Lamellar membraneous whorls were often present near luminal spaces during Spring premigratory and postmigratory, and breeding phases. The endothelial cells of pineal capillaries during Spring and Fall premigratory phases, contained numerous vesicles, some of which were freely dispersed in the cytoplasm while others were fused to the cell membrane, suggestive of transendothelial transport of vesicular substances. PMID- 2591255 TI - [Value of stress TL-201 myocardial single photon emission computed tomography in the diagnosis of coronary artery disease]. AB - Fifteen patients with angina pectoris, seventeen with postmyocardial infarction angina and ten with normal coronary arteries were studied with stress TL-201 single photon emission computed tomography (SPECT). The sensitivity and specificity of SPECT for diagnosis of coronary heart disease were 91% and 90% respectively. SPECT showed better sensitivity (84%) for detecting diseased vessels. The sensitivity of SPECT for identifying one-vessel, two-vessel and three-vessel disease were 80%, 86% and 60%. The sensitivity and specificity of demonstrating involved coronary arteries by identifying the locations of myocardial perfusion defects were 79% and 92% for left anterior descending artery, 90% and 95% for left circumflex artery and 86% and 96% for right coronary artery. For localization of myocardial infarction in the posterior wall, posterior lateral wall, and posterior septum, SPECT is more accurate then ECG. The sensitivity of SPECT in detecting individual vessel is related to the severity of coronary stenosis. The more severe the coronary stenosis, the higher the sensitivity of SPECT. In conclusion, stress SPECT is a noninvasive, highly sensitive and accurate method for detecting and localizing coronary heart disease. PMID- 2591256 TI - [A preliminary report on silent myocardial ischemia detected using ambulatory electrocardiogram monitoring]. AB - 572 cases have been examined with ambulatory electrocardiogram monitoring (AEM). They are divided clinically into three groups, (1) cases after myocardial infarction (2) cases with angina (3) cases without coronary artery disease (CAD). The incidences of silent myocardial ischemia (SMI) in the three groups were 80%, 24% and 3% respectively. The ratios of silent myocardial ischemia to symptomatic myocardial ischemia in groups (1) and (2) were 88.8% and 70.4%. It is shown that silent myocardial ischemia is very frequent in CAD. The article also reviewed and discussed the criteria for diagnosis of SMI, the mechanism of its presence, and its relation to degree of ST segment depression and daily activities. PMID- 2591257 TI - [The significance and state of pre-S2 and antibodies to pre-S2 in 30 cases of acute viral hepatitis type B]. AB - Determination of time sequence of pre-S2 and its antibody response during the symptomatic phase of acute viral hepatitis type B, as well as their relationship to the HBV-markers, was carried out in 30 subjects after the onset of liver damage by means of monoclone antibody-captured enzyme immunoassay were analysed. The results showed that anti-pre-S2 were positive in 80.3% of patients recovering from acute viral hepatitis type B, being higher than the percentage during maximal liver damage (P less than 0.001). Such antibodies were absent in cases showing chronic evolution and were found in less than 8% of chronic hepatitis B cases, with no relation to liver damage. Anti-pre-S2 were detected after the immune clearance of HBsAg and HBV-DNA, and thereafter the anti-HBs were present in 80% of patients after recovery (P less than 0.001). Our observations significantly suggest that anti-pre-S2 may be valuable as a marker of the favourable prognosis of acute viral hepatitis type B and of HBV clearance. They did not play any role in the pathogenesis of HBV-related liver damage. The continuous presence of pre-S2 with the absence of anti-pre-S2, on the contrary, is considered as a characteristic sign and a new information of chronic viral hepatitis type B. PMID- 2591259 TI - [Evaluation of glycated hemoglobin in the early diagnosis of diabetes mellitus]. AB - Although oral glucose tolerance test (OGTT) has been the key examination in early diagnosis of diabetes mellitus, but it still has some problems. It may be affected by some physiological or pathological changes and also requires frequent blood sampling. We investigated the usefulness of measuring the level of glycated hemoglobin (GHb) or HbA1 and HbA1c in screening or early diagnosis of diabetes mellitus. OGTT was performed and fasting levels of HbA1 and HbA1c were measured in 168 subjects. According to the diagnostic criteria of WHO for 75g OGTT, 31 subjects were classified as normal, 35 as having impaired glucose tolerance test (IGT) and 102 as diabetics. The method used for determination of HbA1 and HbA1c was high pressure liquid chromatography (HPLC). The total discovery rate for GHb in diabetic patients was 87%. In patients with fasting level of plasma glucose (FPG) greater than or equal to 8 mmol/L the discovery rate was 100%, while in those with level of FPG less than or equal to 7.94 mmol/L the rate was 80%. Thus, GHb is very useful in screening and early diagnosis of NIDDM (type II), especially diabetes mellitus of the elderly. PMID- 2591258 TI - [Therapeutic effects of polyI:C and prednisone withdrawal followed by polyI:C on chronic type B hepatitis--results of two double-blind randomized trials]. AB - Twenty patients received PolyI:C and twenty patients received inosine in first clinical trial. Final evaluation at 6 months after completion of treatment revealed that SGPT activities fell into normal range or nearly into normal range in 16 (80%) patients of the PolyI:C group and in 8 (40%) patients of the inosine group. These data show that patients treated with PolyI:C have a tendency toward normalization of SGPT activities, but changes of serum HBeAg and DNAP were not significantly different between the two groups. Thirty-five patients were treated with prednisone withdrawal followed by PolyI:C and thirty-five patients received placebo alone in a second clinical trial. Final evaluation at 6 months after completion of treatment revealed that effective rates of reducing serum HBeAg (51.4%) and HBV-DNA (65%) were significantly higher in the treated group than in the control group. It is shown that prednisone withdrawal followed by PolyI:C therapy may be more promising for successful treatment of chronic type B hepatitis than PolyI:C therapy alone. PMID- 2591260 TI - [Peripheral T-lymphocyte subsets changes in patients with endocrine and metabolic diseases]. AB - In this study the authors utilized the OKT monoclonal anti-human T lymphocyte antibodies to determine the normal level of T lymphocyte subsets in the peripheral blood of 30 healthy volunteers, 36 patients with Graves' disease (GD), 4 with hypothyroidism and 30 with diabetes mellitus (DM). It is shown that OKT+3, OKT+4 OKT+8 and OKT+4/OKT+8 ratio of T-lymphocyte subsets in the peripheral blood of 30 healthy volunteers were 72.4 +/- 5.1%, 38.9 +/- 5.2%, 26.8 +/- 4.3% and 1.5 +/- 0.3. In 36 patients with GD OKT+3 was 67.6 +/- 5.8%, OKT+4 was 33.8 +/- 6.6% and OKT+8 was 17.9 +/- 6.1%. These were all significantly lower than those of normal controls (P less than 0.001). OKT+4/OKT+8 ratio was 2.1 +/- 0.6, which was significantly higher (P less than 0.001). The value of OKT+4 and OKT+8 in 10 patients with GD after treatment were markedly elevated. However, the ratio of OKT+4/OKT+8 was significantly decreased (P less than 0.05). OKT+3 of 4 cases of hypothyroidism was 69.7 +/- 3.35%, being similar to that of normal controls (P greater than 0.2). OKT+4 and OKT+8 were 31.73 +/- 4.99% and 18 +/- 2.94% respectively, both of which being markedly decreased (P less than 0.01). The ratio of OKT+4/OKT+8 was 1.97 +/- 0.22, being not significantly elevated (P greater than 0.05). OKT+3, OKT+4 and OKT+8 of 23 cases with DM were 68.8 +/- 7.2% (P less than 0.05), 33 +/- 8.1% (P less than 0.005), and 21.2 +/- 6.5% (P less than 0.001) respectively. All of these were significantly decreased. The ratio of OKT+4/OKT+8 was 1.6 +/- 0.5, being not significantly changed. PMID- 2591261 TI - [A clinical study on myelodysplastic syndrome. Report of 64 cases]. AB - Systematic clinical and laboratory observations of 64 cases of myelodysplastic syndrome (MDS) were made. The results showed that malignant clone already exists in the bone marrow of patients with MDS. Eighteen cases of them have transformed into AML. The rates of transforming into AML in RAEB, RAEB-T and CMML were markedly higher than that in RA. The courses of MDS which transformed into AML from the various types were different. The transformation in RA was obviously longer than those in RAEB and RAEB-T. Two cases transformed into myelofibrosis. Diagnosis of CMML according to the FAB classification criteria revealed that it has two forms. One shows only increase of mature monocytes and it has no relation with the types of acute leukemia to be transformed. It is considered as a reactive monocytosis. The other form, in addition to increase of mature monocytes, also has increase of a few monoblasts and promonocytes. These are considered as true CMML and usually quickly developed into M4 or M5 which are related with monocytes. PMID- 2591262 TI - [Nd-YAG laser treatment of tracheobronchial lesions]. AB - From January 1987 to May 1988, 32 cases with tracheobronchial lesions were treated with Nd-YAG laser. Complete restoration of the airway was achieved in one case of leiomyoma, adenoma, carcinoid and mucous epithelioma each, 2 cases of polyp and 7 cases of granuloma. Significant restoration was seen in one case of granuloma, 2 cases of hematoma and papilloma, each, 3 cases of amyloidosis and partial restoration in one case of granuloma. The remaining 10 cases with squamous cell carcinoma and adenocarcinoma with severe airway obstruction were treated by Nd-YAG laser for palliative purpose only. Four of them revealed significant remission and 6 responded with partial remission. No severe complication was observed during or after the procedures. Nd-YAG laser treatment provides a new curative method avoiding resection of the lung in benign lesions and a palliative therapy for unresectable obstructive malignant tumors. PMID- 2591263 TI - [Multiple primary bronchial carcinoma. A case report of three separate synchronous primary cancers and a review of literature]. AB - Fibreoptic bronchoscopy was performed in 677 patients with primary bronchial carcinoma during a period from October 1978 to January 1988. In one of them three separate synchronous bronchial carcinomas were found in the lungs. Two of these tumours were radiographically occult. The diagnoses of squamous cell carcinoma of the lung were verified histologically by materials obtained at fibreoptic bronchoscopy. This finding emphasizes the importance of careful bronchoscopic examination of the whole bronchial tree before surgical treatment of lung cancer. The literatures of 41 cases with multiple primary bronchial carcinoma were reviewed. PMID- 2591264 TI - [A study on the pathogenesis of hepatolenticular degeneration using an in vitro model]. AB - Hepatolenticular degeneration (HLD) as an autosomal recessively inherited disease has been known to be associated with by copper metabolic dysfunction. Its primary genetic defect is still not clear. The average copper content of HLD cells was found to be approximately threefold as much as that of normal cells in the authors previous studies. Cultured fibroblasts were used to serve as an in vitro model to investigate the primary molecular defects. The distribution of intracellular copper in the proteins of HLD cells were examined. The cell lysates were fractionated by gel chromatographic filtration. The copper concentration of the column fractions revealed that the copper binding character was altered in HLD cells. A decreased ratio of copper to proteins was observed in cytoplasmic proteins having a molecular weight greater than 300,000. There was more copper specifically bound to the lower molecular weight compounds in the HLD cells. The results of this laboratory technology suggested that this might serve as a method for establishing the early diagnosis of this disease. PMID- 2591265 TI - [A family of scapula-back type of x-linked recessive muscular dystrophy]. AB - In this paper are described seven men with a scapula-back type of x-linked recessive muscular dystrophy in a family. Onset began in boyhood. The scapula back muscles were affected, but the calf muscles were normal. All of the patients were able to walk. The oldest patient was thirty-seven years old. Muscular dystrophy was confirmed by electro-myography (EMG), pathologic and CPK examinations. Pedigree analysis indicated x-linked recessive inheritance. PMID- 2591266 TI - [X-linked recessively inherited peroneal muscular atrophy]. AB - This article presents a pedigree of 80 members of which there are 13 patients (13 males) with peroneal muscular atrophy. The analysis of this pedigree shows that an affected male married to a normal female will have normal son(s) and carrier daughter(s). The normal son(s) will have normal offspring, but half the sons of the carrier-daughter(s) will be affected. The pathogenic genes of affected males are transmitted to their daughters, but not to their sons. So this inheritance is of X-linked recessive type. This is the first report of X-linked recessively inherited peroneal muscular atrophy in china. PMID- 2591267 TI - [Serum complement composition of myasthenia gravis]. AB - Serum complements of C1q C1, C4, BF, C1-INH and C5 were measured by single immunodiffusion in 54 patients with myasthenia gravis (MG), 46 normal control (NC) and 42 cases of other neurological disorders. It was found that C1-INH, C5 levels in MG were significantly higher than that in other groups (P less than 0.01). The serum levels of C1-INH, C5 were not related to the clinical type and the stage of the illness. These data suggest that endplate receptors might be disrupted through complement mediated immunoreaction. PMID- 2591268 TI - [The effects of ligustrazine, aspirin and beta-histine on platelet aggregation in patients with acute ischemic stroke]. AB - With a auto-balanced terbidimeter, the effects of ligustrazine, aspirin and betahistine on platelet aggregation were studied in 45 patients with acute ischemic stroke. The adopted parameters were: 1) the maximal aggregation (Amax), 2) the maximal aggregation velocity (Vmax), 3) the effective disaggregation rate in 5 minutes (DA 5), 4) the inhibition rate of aggregation given by drugs (IR), and 5) the concentration causing 50% inhibition of aggregation (IC 50). The results indicated that these three drugs could inhibit platelet aggregation both in vivo and in vitro. Aspirin could promote the aggregated platelets disaggregation in vivo and ligustrazine, in vitro. Regarding the effects on inhibiting platelet aggregation in vitro, ligustrazine was the most noticeable among the 3 drugs and aspirin was more effective than betahistine. The IC50 of ligustrazine, aspirin and betahistine were 0.568 mg/ml, 1,286 mg/ml and 1.722 mg/ml respectively. The authors considered that all three drugs possessed anti platelet effects but they showed some differences among them. PMID- 2591269 TI - [A study of erythrocyte deformability using an ektacytometer in normal adults and in patients with acute cerebral infarction]. AB - We studied the erythrocytes deformability with an ektacytometer made in China in 55 normal adults and in 22 patients with acute cerebral infarction (ACI). The results showed that sex has no influence upon the deformability of RBC in normal adults. The deformability of RBC decreases with the age, but there is no significant difference between different age groups. The deformability of RBC in ACI decreases obviously. It may be one of the factors that increase the whole blood viscosity in ACI. The measurement of RBC deformability with ektacytometer is simple, fast and only 20u mu whole blood needed. The ektacytometer is a valuable tool in experimental and clinical researches. PMID- 2591270 TI - [Application of the electrocochleogram in Meniere's syndrome]. AB - The results of evoked potentials (ECOG and ABR) in 92 patients with complaints of dizziness and vertigo were analysed. There were 69 cases of Meniere's syndromes, among which 45 cases (75%) showed increase of the summating potentials. In 22 cases the SP/AP rate exceeded 0.37 of 23 cases of vertebral basilar arteria TIA, one case showed negative wave SP increase, one case showed SP/AP ratio exceeding 0.37 and 3 cases showed prolonged latency of I wave in ABR. It was pointed out the simultaneous use of ECOG and ABR would be of help in identifying the most probable cause of dizziness and vertigo and this method would be worthy to be used on a much broader scale. PMID- 2591271 TI - [Depressive state complicated with chronic renal failure treated by continuous ambulatory peritoneal dialysis]. AB - Thirty two cases of chronic renal failure with Continuous Ambulatory Peritoneal Dialysis (CAPD) hospitalized from November, 1984 to July, 1986 were investigated by interview, Hamilton Depression Scale (HAMD) and Symptom Check List (SCL-90). Results revealed that the occurrence of depression among dialyzed patients was 56.3%, i.e. 18 patients with high total score of HAMD belonged to organic affective syndrome defined by DSM-III. Causes of developing depression during CAPD were evaluated and analyzed. Authors consider that depression should be viewed as interaction of genetic, psychosocial and neurobiological variables. PMID- 2591272 TI - [A study on the formation and application of thought concepts among schizophrenics]. AB - According to different studies and observations scholars have put forward many theories and explanations about the schizophrenic thought disorder, but conclusions varied. In order to explore schizophrenic thought disorder, the authors designed psychological experiment on the formation and application of concept. All subjects were schizophrenic 44 in chronic group 30 patients in acute group and 33 normal adult and 30 children as controls. The results of the experiment revealed that: (1) The thought disorder of schizophrenic is mainly the degeneration of thought development with concrete thought form. As the course of illness goes on, the thinking ability of chronic schizophrenics equal that of children younger than 14. (2) result does not support the theory of overinclusion or (3) experiment might provide reference for the clinical diagnosis. PMID- 2591273 TI - [A comparative study of memory using WMS-R in cases with brain damage and normal subjects]. AB - The data of comparative study using WMS-R in 54 cases with Brain damage, and in 52 normal subjects, were presented. The main findings revealed, (1) Overall, various impairments of memory function were observed, but there were somewhat in varying degrees of memory impairment from different category of disease. (2) More serious memory impairment was seen in epileptic group, metabolic disease group, and degenerative disorder group successively. (3) No correlation between the memory impairment and sex, as well as the morbid course, was found. It seems to be relate to the disease itself. PMID- 2591274 TI - [A study on serum creatine phosphokinase and type A behavior in schizophrenia]. AB - The CPK levels of 79 patients with schizophrenia (36 males and 43 females and 88 normal control subjects (53 males and 35 females) were assessed. The result shows that the CPK level of the patients with acute schizophrenia (307.33 Iu/L) was significantly higher than that of the normal control subjects (160.51 Iu/L) (t = 3.534, N21, 88, P less than 0.01) and the CPK level of male schizophrerines rose more significantly. Meanwhile, some cases from the two groups were examined using the Type A behavior pattern inventory. No significant difference was shown between these two groups. It is considered that the change of some enzymes within the blood may affect the genetic vulnerability to schizophrenia. PMID- 2591275 TI - United we stand. PMID- 2591276 TI - Reliability of colonoscopy. AB - In an effort to determine the reliability of colonoscopy the authors retrospectively reviewed preoperative colonoscopic findings and compared them with the postoperative pathologic specimen reports. Only lesions greater than 0.5 cm were included in the comparison. Over a 13-year period, 429 patients with colorectal cancer underwent preoperative colonoscopy. Four hundred thirteen (97 percent) of the colonoscopic examinations correlated with the pathologic specimen, but, in 16 cases (3 percent), lesions were missed. In total, 17 adenomatous polyps and 3 cancers were found in the surgical specimens that were not documented at colonoscopy. Eighteen patients had total preoperative colonoscopy and total abdominal colectomy, which makes for a reliable model to judge the accuracy of colonoscopy. In these 18 patients, 17 of the pathologic specimens correlated with the endoscopic findings, which yields an accuracy rate of 94 percent. Blind areas in the colon, plus misjudgment that the scope had reached the cecum, are responsible for the majority of colonoscopic errors. PMID- 2591277 TI - Age and sex and anorectal manometry in incontinence. AB - Although the prevalence of fecal incontinence is greater in women compared with men and in elderly subjects compared with younger subjects, data regarding the influence of age and sex on anorectal performance in continent and incontinent patients are conflicting. The authors, therefore, investigated age- and gender related changes in anal resting and squeeze pressure as well as in sphincter relaxation after rectal balloon distention in 75 patients with fecal incontinence of different pathogenesis and in 99 continent patients by multichannel anorectal manometry. As a group, incontinent patients usually exhibit lower pressure profiles than do continent patients regardless of age and gender; however, both the resting pressure of the internal anal sphincter and the voluntary contractile pressure of the external anal sphincter are decreased with age, and both are lowered in women compared with men. Sphincter relaxation and perception of gastrointestinal events are not altered in incontinent patients, and they are not different between men and women or between elderly and younger patients. PMID- 2591278 TI - Anorectal complications of vaginal delivery. AB - The incidence of anorectal complications following vaginal delivery was studied in 20,500 women. One thousand forty (5 percent) of all normal vaginal deliveries resulted in episiotomy with third- and fourth-degree extension or a fourth-degree perineal tear. Of these fourth-degree lacerations, 101 patients (10 percent) experienced wound disruption after primary repair. Sixty-seven patients (66 percent) experienced wound disruption that required surgical correction. Anorectal complications were anal ulcer, anorectal abscess, sphincteric disruption, and rectovaginal fistula. Surgical correction of these complications resulted in satisfactory outcome. PMID- 2591279 TI - Primary repair vs. colostomy for the treatment of penetrating colon injuries. AB - The charts of 81 consecutive patients with penetrating colonic trauma were reviewed. Sixty-five patients were considered for evaluation. Penetrating abdominal trauma index, associated injuries, length of operative procedure, wounding agent, length of hospital stay, method of treatment, and septic complications were evaluated. Twenty-eight patients were treated with colostomy at the site of injury: five with diverting colostomy proximal to repair, 30 with primary repair (either single or multiple injuries), and two with exteriorization and early drop back. Overall septic morbidity was 15 of 65 (23 percent) patients. No statistically significant difference was found in morbidity between colostomy, 9 of 33 (27 percent), and primary repair, 6 of 30 (20 percent). The two patients with exteriorized repairs had no morbidity. No deaths were reported among the 65 patients studied. Thirty-two of the 33 (97 percent) colostomies were later closed with morbidity in 7 of 32 (22 percent). The mean length of stay for primary repair patients was 10.3 +/- 2.8 days and for colostomy patients, 25.7 +/- 3.8 days, counting days for both initial and colostomy closure admissions (P less than .05). Colostomy was not mandated by anatomic location or number of colonic injuries, circumference of colonic wall involved, presence of fecal contamination, or involvement of mesenteric blood supply. This study indicates that primary repair does not carry an increased risk of septic complications and saves the patient the significant risk and increased hospital stay of colostomy closure. Prospective studies addressing this area are indicated. PMID- 2591280 TI - Ileoanal anastomosis with interposition of the ileal 'Kock pouch'. Preliminary results. AB - For patients needing proctocolectomy, there are several alternatives available today for the previously dominating conventional ileostomy. Currently, the ileal pouch-anal anastomosis attracts major interest. Various reservoir procedures have been proposed, but the ideal reservoir design is still debated. The double-folded ileal reservoir (Kock pouch) has a large capacity, low pressure, and is expandable. It is successfully used for the construction of continent ileostomies, continent urostomies, and for replacing the urinary bladder by connecting the reservoir to the urethra. In view of these facts, it was decided to interpose the Kock pouch between the ileum and the anus after colectomy and mucosal proctectomy in a small number of patients, and to study and evaluate its merits in this position. Six consecutive patients formed the study group. Three months after ileostomy closure the stool frequency was 4 every 24-hours, range 3 to 5, and remained so during the follow-up period. All patients could sleep through the night without bowel movements or soiling. None of the patients used pads. The capacity of the reservoir increased from a mean of 100 ml preoperatively to 550 ml one year after ileostomy closure. The large reservoir capacity and the low pressure can explain the good functional results. PMID- 2591281 TI - DNA content and mucosal dysplasia in ulcerative colitis. Flow cytometric analysis in patients with dysplastic or indefinite morphologic changes in the colorectal mucosa. AB - In an unselected population of 108 patients with ulcerative colitis in an ongoing endoscopic cancer surveillance program, high-grade dysplasia was diagnosed in 3, low-grade dysplasia in 11, and mucosal changes indefinite for dysplasia in 11 patients. The abnormal biopsy specimens from these 25 patients and samples from other parts of the large bowel obtained at the same examination were investigated by flow cytometric DNA analysis. One hundred thirty-six of 160 samples (85 percent) gave evaluable DNA histograms and, accordingly, 23 patients were retrospectively investigated. Six patients (26 percent) showed aneuploidy (abnormal DNA stemlines) and 1 had possible aneuploidy. All 3 patients with high grade dysplasia showed aneuploidy (or possible aneuploidy) preceding or coexisting with the severe dysplastic changes. In 1 of these patients, the presence of aneuploidy preceded two diploid carcinomas. One patient was found to have had aneuploidy for seven years without evident malignant transformation. Further prospective studies are necessary to determine the value of DNA analysis in relation to morphologic examination in surveillance of patients with ulcerative colitis. PMID- 2591282 TI - Ischemic colitis as a cause of massive lower gastrointestinal bleeding and peritonitis. Report of five cases. AB - Vascular disorders of the colorectum are considered rare in Taiwan, however, recently the authors encountered five cases of ischemic colitis, all in men over 50 years of age. Cases one and five involved stricture, case two was secondary to obstructive colon cancer, and case three was of the gangrenous type presenting with peritonitis due to colonic perforation. Case four was of the transient type with acute massive lower gastrointestinal bleeding secondary to traumatic shock. All five patients were treated successfully by resection. PMID- 2591283 TI - Primary rectal lymphoma and malignant lymphomatous polyposis. Two cases illustrating current methods in diagnosis and management. AB - Two cases of colorectal lymphoma are presented. Preoperative histologic diagnosis is difficult and examination of the fresh specimen using immunocytochemical and gene rearrangement techniques are necessary to establish the precise nature of the lesion. Surgical excision is the mainstay of treatment for localized lymphoma of the colorectum and chemotherapy for malignant lymphomatous polyposis. PMID- 2591284 TI - Colonic volvulus. PMID- 2591285 TI - [Spontaneous fusion of cells without centrioles, formed as a result of tripolar mitosis in cell culture]. PMID- 2591286 TI - [Increased sensitivity to Ca2+ ions of contractile proteins of portal vein smooth muscle cells in rats with spontaneous hypertension]. PMID- 2591287 TI - [Characteristics of various types of atypical miniature end-plate currents in rats]. PMID- 2591288 TI - [The functional significance and stoichiometry of cellular mosaics of squamous epithelial cells]. PMID- 2591289 TI - [Detection of flat charged clusters on the surface of gamma-crystalline protein]. PMID- 2591290 TI - [Water soluble protein components of preparations of bovine outer rod segments bound with melittin-sepharose in a Ca2+-dependent manner]. PMID- 2591292 TI - [Cardiotrophic activity of peptide preparations from tissues of hibernating squirrels]. PMID- 2591291 TI - [A catalytic component of calmodulin-independent adenylate cyclase from bovine brain. Amino acid sequence of a protein and nucleotide sequence of corresponding cDNA]. PMID- 2591293 TI - [The effect of low-molecular weight nuclear RNA on the cell cycle during asynchronous embryonic fission]. PMID- 2591294 TI - [The dielectric breakdown of membranes during cryopreservation of biological objects]. PMID- 2591295 TI - [Analysis of prostaglandins using high performance liquid chromatography of their dansylhydrazides]. PMID- 2591297 TI - Effect of glucarolactam on low-dose nephrotoxicities of dibekacin and gentamicin in Fischer rats. AB - Intramuscular administration of dibekacin or gentamicin to Fischer rats at doses of 10, 20 and 40 mg/kg for 11 days gave polyuria, enzymuria and cytauria. These changes were suppressed completely or partially by the simultaneous administration of glucarolactam sodium or potassium salt. The ameliorating results were supported by serum and histopathological analyses on day 12. A rise in BUN and serum creatinine levels was partially or completely suppressed and histopathological scores were improved by co-administration of glucarolactam salts. PMID- 2591296 TI - Reduction of dibekacin-induced nephrotoxicity in the rat by the formation of N alkylsulfonate derivatives. AB - Seven N-alkylsulfonate derivatives of an aminoglycoside antibiotic, dibekacin, were prepared and their nephrotoxicity was examined. Using water-supplied and water-depleted rats and the BUN value as a nephrotoxic measure, dibekacin-di-N methanesulfonate, pentasodium dibekacin-penta-N-methanesulfonate, -penta-N ethanesulfonate, disodium dibekacin-di-N-methanesulfonate sesquisulfate, disodium and dipotassium dibekacin-di-N-ethanesulfonate sesquisulfates and sodium dibekacin-mono-N-ethane-sulfonate disulfate showed low nephrotoxicity as compared to that of the original dibekacin sulfate. Notably, dibekacin-di-N methanesulfonate caused little change in the BUN value and was bioactive in vitro but not active in vivo against a Pseudomonas aeruginosa infection model in mice. Among the bioactive N-alkylsulfonates in vivo, disodium and dipotassium dibekacin di-N-ethanesulfonate sesquisulfates showed a lower degree of elevation of BUN, urine volume and urine protein, lower mortality and better body weight gain than those of dibekacin sulfate during consecutive treatment for 12 and 28 days. PMID- 2591298 TI - Effect of glucarolactam on ototoxicity of aminoglycoside antibiotics in guinea pigs. AB - Intramuscular administration of glucarolactam in the form of aminoglycoside salt to guinea-pigs protected the experimental ototoxicity caused by high dosing of aminoglycoside antibiotics. The protection was evidenced by the pinna reflex threshold and histochemical examinations of hair cells of cochlea as well as body weight gain. The degree of protection differed with the aminoglycosides, and high protection was observed for dibekacin, gentamicin, tobramycin, followed by kanamycin and bekanamycin. However, protection was weak or not observed when glucarolactam was administered as a mixture of glucarolactam potassium and aminoglycoside sulfate. Serum analysis of the guinea-pigs on day 14 post administration as a measure of nephrotoxicity revealed that glucarolactam suppressed the elevation of BUN and serum creatinine caused by the aminoglycosides. The protective effect of glucarolactam on the aminoglycoside induced nephrotoxicity in the dehydrated rats did not differ between the salt and the mixture. No difference in the in vivo antibiotic activity against bacterial infections of mice was observed between the salt and the mixture. PMID- 2591299 TI - Comparative nephrotoxicity of ribostamycin and gentamicin in rats evaluated by urinalysis. AB - The nephrotoxicity of ribostamycin and gentamicin was compared by urinalysis using 18 parameters. When a dose of 40 mg/kg per day was administered intramuscularly to Fischer rats for 14 days, ribostamycin caused little change of parameters in urine volume, urine osmolality, urine protein, maltase and beta 2 microglobulin. A slight increase with ribostamycin was observed in alpha fucosidase, beta-N-acetylglucosaminidase, leucine aminopeptidase, lactic dehydrogenase (LDH) and potassium, and a moderate increase was observed in acid phosphatase and alkaline phosphatase. On the other hand, gentamicin caused a large alteration in most parameters. Both antibiotics caused a change of the isoenzyme pattern of LDH1-5, but the pattern with ribostamycin was much closer to the normal pattern than with gentamicin. When a dose of 80 mg/kg of ribostamycin was compared with 10 mg/kg of gentamicin, alteration of urinary parameters was almost comparable. Histopathological observations of the kidney specimens of rats given 40 mg/kg per day showed no histological damage with ribostamycin except for a slight increase and enlargement of lysosomes of the proximal epithelial cells. However, significant histological damage was observed with gentamicin, consistent with the results obtained from urinalysis. Renal accumulation of ribostamycin at a single dose of 20 mg/kg was three times less than that of gentamicin. Ribostamycin caused slightly less nephrotoxicity in rats than kanamycin and far less than dibekacin at an equal dosage of 40 mg/kg per day for 14 days. PMID- 2591300 TI - An experimental meningitis with Streptococcus pneumoniae in rats: therapeutic effect of aspoxicillin and its penetration into CSF. AB - An experimental meningitis model was produced in rats with Streptococcus pneumoniae Type III and used to evaluate the therapeutic effect of aspoxicillin in comparison with piperacillin, mezlocillin and ampicillin. At the same time, their bactericidal activities and pharmacokinetics in cerebrospinal fluid (CSF) were determined. The experimental meningitis model was prepared by intracisternal inoculation of the organism. The rats in this model began to die 2 days after the infection and all died within 5 days. Histological examination also revealed that this model was a fatal pneumococcal meningitis model in rats. The concentrations of these penicillins in CSF of the infected rats determined by the high performance liquid chromatography method were significantly increased by bacterial infection. Of these drugs, ASPC gave the highest penetration into the infected CSF and the longest persistency in CSF. In a comparison of the bactericidal activity of these penicillins in this model, aspoxicillin at a dose of 20 mg/kg inhibited the regrowth of bacteria in CSF 24 h after administration, but the other three penicillins did not. To conclude, in this new experimental meningitis model in rats, aspoxicillin showed an excellent therapeutic effect due to its stronger bactericidal action and favourable pharmacokinetic properties. PMID- 2591301 TI - In vitro activity of netilmicin alone and in combination with azlocillin, mezlocillin and imipenem against 149 coagulase-negative staphylococci. AB - Coagulase-negative staphylococci (CNS) have long been regarded as innocuous skin commensals with little pathogenic potential but they have recently become, under appropriate conditions, an important cause of infections. In fact, infections caused by CNS are an increasing problem especially, but not exclusively, in immuno-compromised patients. A total of 149 strains of CNS were identified from 47 patients admitted to the Haematology Department of Pescara Hospital from October 1986 to November 1987. The strains, isolated from different parts of the body and characterized by their methicillin susceptibility, were classified by API-Staph in 11 different groups. MICs and MBCs of netilmicin alone and combined with azlocillin, mezlocillin and imipenem were studied. For all combinations FIC and FBC indices were determined. The killing kinetics of the drugs mentioned above were also determined. Except for a few microorganisms (less than 5%), the associations showed a synergic or additive effect. PMID- 2591302 TI - Efficacy and safety of cefotetan in the treatment of complicated urinary tract infections: clinical experience in a selective and single study. AB - A single, selective study was performed in order to evaluate the efficacy and safety of cefotetan in the treatment of complicated urinary tract infections (UTI). Of 34 pre-treatment isolated strains, 60% were pluri-resistant to other antibiotics (ampicillin, carbenicillin, piperacillin, cefalotin, aztreonam) but only 21.2% to cefotetan. Pseudomonas aeruginosa and enterococci were resistant to cefotetan. Escherichia coli was the common strain isolated (50%). Nineteen adult patients, with complicated UTI caused by sensitive organisms, were treated with a 1 g intramuscular (i.m.) daily dose. Duration of treatment ranged from 5-15 days, with a mean of 13.75 days. Within 24-48 h and 30 days post-therapy, the infection was cured in 84% and 52% of patients, respectively. Reinfection, relapse or super infection occurred in 42% of the cases. In only one patient, the infecting organism did not respond to treatment. The clinical response was evaluated in only seven patients with symptomatic UTI. Six of them (85.7%) were cured after therapy and the cure persisted at follow-up. In most cases, the adverse reactions were local, mild and negligible. In only 15.8% and 10.5% of patients, side effects (diarrhoea, headache, abdominal pain, tachycardia, chill, pain and erythema in the injection site) were severe and moderate. In these cases, the adverse reactions were reversible when the therapy was discontinued. The relationship between treatment and side-effects was doubtful in two cases. It is concluded that cefotetan, administered at 1 g i.m. daily dose, is effective in treating complicated UTI caused by sensitive organisms, pluri-resistant to other antibiotics. PMID- 2591303 TI - Influence of CDP-choline administration on the aortic wall lesions in dietically hypercholesterolaemic rabbits: a morphometric evaluation. AB - In New Zealand rabbits subjected for a 2 month period to a 1% or 2% hypercholesterolic diet, larger intimal involvement and histologically heavier lesions were observed in the animals on a hypercholesterolic diet. The intimal involvement was larger in the aortic arch. In groups of rabbits simultaneously subjected to similar diets and to i.v. CDP-choline injections, the intimal involvement appeared reduced (p less than 0.01) both in the arch and in the descending tract of the thoracic aorta. PMID- 2591304 TI - [Gallbladder polyps and gallbladder stones]. AB - Over a period of 32 years 689 patients with upper abdominal symptoms were examined radiologically at least twice for gall-bladder polyps and stones. All were without evidence of stones initially, but 181 had gall-bladder polyps on first examination. During a mean observation period of 9 1/2 years gall-bladder stones occurred in 18% (pigment stones in about 24%, solitary cholesterol stones in 30% and multiple ones in 46%), regardless of the presence or absence of gall bladder polyps. There was no evidence for a change from polyps to stones. Cholesterolosis runs through four stages in the course of decades; accumulation of cholesterol esters in subepithelial foam-cell nests is characteristic. 95% of gall-bladder polyps are cholesterol polyps which gradually empty. Prophylactic cholecystectomy for gall-bladder polyps is justified only if they are more than 10 mm in diameter. PMID- 2591305 TI - [Histiocytosis X. Problems of differential diagnosis in adults]. AB - A now 20-year-old man has been suffering from diabetes insipidus for four years. Two years ago a tumour in the hypophyseal stalk-hypothalamus region had been removed, but no definitive histological diagnosis could be established. When aged 19 he developed cutaneous changes which for the first time led to histiocytosis being suspected. Also for the first time, multiple small foci were noted in both lungs. Histological examination of a transbronchial lung biopsy demonstrated histiocytosis X. No specific treatment is being considered at present, because the patient is symptom-free and has normal lung function. PMID- 2591306 TI - [Porocephalosis]. AB - A diagnostic laparotomy was performed in a bush hospital on a 35-year-old African woman with a 10-year history of abdominal pain. It revealed hundreds of small calcified masses, 1-2 cm in diameter, throughout the abdominal cavity. Histological examination of a biopsy specimen from the peritoneum showed nearly complete calcification of tissue nodules with questionable parasite residues. A plain X-ray film of the abdomen, which it had been impossible to obtain earlier, had comma- and horseshoe-like calcifications which were interpreted as calcified residues of Armillifer, a parasite endemic in snakes. The patient used to eat snake meat frequently. There is no causal treatment of this infestation, termed pentastomiasis or porocephalosis. PMID- 2591307 TI - [Patient understanding of disease support concerning psychiatric treatment]. PMID- 2591308 TI - [ESWL in pancreatic duct stones]. PMID- 2591309 TI - [Etiology of "microscopic colitis"]. PMID- 2591310 TI - [Persistence of a positive lymphocyte stimulation test in cephalosporin-induced anaphylactic shock and the following neutropenia]. PMID- 2591311 TI - [Malaria on the Turkish Riviera]. PMID- 2591312 TI - Induction of functional cytodifferentiation in the epithelium of tissue recombinants. I. Homotypic seminal vesicle recombinants. AB - Functional cytodifferentiation of seminal vesicle epithelium was investigated in tissue recombinants. Neonatal rat and mouse seminal vesicles were separated into epithelium and mesenchyme using trypsin. Epithelium and mesenchyme were then recombined in vitro to form interspecific rat/mouse homotypic recombinants. Growth as renal grafts in adult male athymic mice resulted in seminal vesicle morphogenesis in 70% of the recombinants (the remaining 30% failed to grow). Functional cytodifferentiation was judged by the expression of the major androgen dependent secretory proteins characteristic of the seminal vesicles of adult rats and mice. Antibodies specific for each of these proteins were used to screen tissue sections by immunocytochemistry and to probe protein extracts by immunoblotting techniques. The heterospecific recombinants synthesized the full range of seminal vesicle secretory proteins that typifies the species providing the epithelium of the recombinant, not the mesenchyme. There was little functional variation between individual recombinants. The time course of development corresponded to that of intact neonatal seminal vesicles grown under the same conditions. Morphogenesis and functional cytodifferentiation were not evident after one week, but were well advanced after two weeks. Seminal vesicle recombinants grown for three weeks were indistinguishable morphologically and functionally from normal adult seminal vesicles. In addition, the ability of adult seminal vesicle epithelium to be induced to proliferate was examined. In association with neonatal seminal vesicle mesenchyme, the epithelium of the adult seminal vesicle proliferated and retained its normal functional activity. Thus, seminal vesicle functional cytodifferentiation can be faithfully reproduced in homotypic tissue recombinants. The methods used in this study will be used to investigate seminal vesicle development in instructive inductions of heterotypic epithelia. PMID- 2591313 TI - Induction of functional cytodifferentiation in the epithelium of tissue recombinants. II. Instructive induction of Wolffian duct epithelia by neonatal seminal vesicle mesenchyme. AB - When grown as renal grafts in adult male hosts, the upper (cranial), middle and lower (caudal) portions of fetal mouse and rat Wolffian ducts developed into epididymis, epididymis plus ductus deferens, and seminal vesicle, respectively. In heterotypic tissue recombinants, the epithelia from upper and middle Wolffian ducts were instructively induced to undergo seminal vesicle morphogenesis by neonatal seminal vesicle mesenchyme. Functional cytodifferentiation was examined in these recombinants using antibodies against major androgen-dependent, seminal vesicle-specific secretory proteins. The instructively induced Wolffian duct epithelia synthesized normal amounts of all of the secretory proteins characteristic of mature seminal vesicles, as judged by immunocytochemistry on tissue sections and gel electrophoresis plus immunoblotting of secretions extracted from the recombinants. In heterospecific recombinants composed of rat and mouse tissues, the seminal vesicle proteins induced were specific for the species that had provided the epithelium. This showed that the seminal vesicle epithelium in the recombinants was derived from instructively induced Wolffian duct epithelium and not from epithelial contamination of the mesenchymal inductor. Upper Wolffian duct epithelium, instructively induced to undergo seminal vesicle morphogenesis, did not express epididymis-specific secretory proteins, showing that its normal development had been simultaneously repressed. PMID- 2591314 TI - Gene expression during mammalian oogenesis and early embryogenesis: quantification of three messenger RNAs abundant in fully grown mouse oocytes. AB - Ribonuclease protection assays have been used to quantitatively assess changes in steady-state levels of specific mRNAs during oogenesis and early embryogenesis in mice. The mRNAs encode ZP3 (a glycoprotein that serves as a sperm receptor), LDH B (heart-type lactate dehydrogenase), and MOM-1 (a protein of unknown function). MOM-1 and LDH-B are expressed in a variety of adult mouse tissues and midgestation embryos, whereas ZP3 expression is restricted completely to oocytes. All three mRNAs are expressed by growing mouse oocytes and accumulate to unusually high levels in fully grown oocytes as compared to somatic cells; 240,000, 200,000 and 74,000 copies mRNA per fully grown oocyte for ZP3, LDH-B and MOM-1, respectively. Steady-state levels of LDH-B and MOM-1 mRNA undergo a modest decline (approximately 20-40%) during ovulation when fully grown oocytes become unfertilized eggs and, in general, mirror the reported change in poly(A)+RNA levels during this period of development. On the other hand, the level of ZP3 mRNA declines dramatically (approximately 98%) during ovulation, from approximately 240,000 copies per oocyte to approximately 5000 copies per unfertilized egg, and ZP3 mRNA is undetectable in fertilized eggs (less than 1000 copies per fertilized egg). MOM-1 mRNA is expressed at relatively low levels in morulae (approximately 2000 copies per embryo) and blastocysts (approximately 5000 copies per embryo), whereas ZP3 mRNA remains undetectable (less than 1000 copies per embryo) at these stages of preimplantation development. These findings are discussed in the context of overall gene expression during oocyte growth, meiotic maturation and early embryogenesis in mice. PMID- 2591315 TI - Expression of microinjected hsp 70/CAT and hsp 30/CAT chimeric genes in developing Xenopus laevis embryos. AB - The expression of microinjected chimeric genes containing Drosophila hsp 70 and Xenopus hsp 70 and hsp 30 promoters linked to the reporter gene coding for bacterial chloramphenicol acetyltransferase (CAT) was examined during early development of Xenopus laevis. Heat-inducible expression of fusion genes containing either the Drosophila hsp 70 promoter (1100 bp) or the Xenopus hsp 70 promoter (750 bp) was first detectable after the midblastula stage of development. This coincides with the embryonic stage at which the endogenous hsp 70 gene is first heat-inducible. A Xenopus hsp 30/CAT fusion gene containing 350 bp of promoter sequences was also heat-inducible after the midblastula stage unlike the endogenous hsp 30 genes which were not heat-inducible until the early tailbud stage (stage 23-24). Sequences that are present within either the coding or 3' region of the hsp 30 clone do not cause the microinjected hsp 30 gene to be developmentally regulated in a normal manner. Additionally, microinjected hsp 30 gene sequences have no effect on the developmental regulation of endogenous hsp 30 genes which continue to be activated at the tailbud stage of development. Our data suggest, that an inhibitory system, which may control the expression of the endogenous hsp 30 gene during development, does not regulate the expression of the injected hsp 30 gene. PMID- 2591316 TI - Characterization of proteins secreted by sheep oviduct epithelial cells and their function in embryonic development. AB - The role in early development of proteins secreted by oviduct epithelial cells has been investigated. Secreted proteins devoid of serum contamination have been produced by the surgical removal and immediate incubation of oviduct cells in [35S]methionine-containing medium. After electrophoretic separation, secreted polypeptides could be divided into those that were secreted uniformly throughout the oestrous cycle and a second class that showed a cyclical pattern of secretion. The first class of proteins represented a small proportion of total output whilst the predominant second class was composed mainly of polypeptides of Mr 92 and 46 x 10(3), respectively. Both of these polypeptide species, referred to as sheep oviduct proteins 92 and 46 (SOP 92, SOP 46), are detected only during the first 4 to 5 days after oestrus when the embryos are located in the oviduct. Oviduct cells collected at oestrus and maintained thereafter in culture secrete the same pattern of proteins and follow the same time course as their counterparts in vivo. The interaction between the oviduct proteins and the developing embryo was studied firstly by determining whether any of the secreted proteins bound to the zona pellucida. The results of iodination studies showed that two polypeptides of Mr 92 and 46 x 10(3), respectively, were bound to the zona pellucida of eggs removed from the oviduct but were absent from eggs that had not had contact with the oviduct epithelium. That these newly acquired proteins represent SOP 92 and 46 is suggested by their electrophoretic mobility and their ability to bind to the zona of follicular eggs when added in vitro and by the fact that they both disappear from the zonae of embryos after exit from the oviduct. The collection of unlabelled secreted proteins enabled us to produce a monoclonal antibody, which was used in the second series of experiments on oviduct-embryo interactions. The results confirmed that SOP 92 binds to the zona pellucida and moreover showed that this protein crosses the zona and becomes associated with the individual blastomeres of the developing embryo. These findings provide evidence that the mammalian oviduct probably plays a direct role in supporting embryonic development through specific polypeptides produced by its epithelium. PMID- 2591317 TI - Cross-species recognition of tectal cues by retinal fibers in vitro. AB - The retinae of vertebrates project in a topographic manner to several visual centers of the brain. The formation of these projections could depend on the existence of position-specific properties of retinal and target cells. In this study, we have tested the in vitro growth of mouse retinal fibers on membranes derived from various regions of the embryonic superior colliculus, a main target of the retina in this species. Fibers had the choice of elongating on membranes taken from either the anterior or the posterior half of the superior colliculus. Fibers from temporal areas of the retina prefer to elongate on anterior collicular membranes, while fibers from nasal areas do not show a preference. These phenomena are observed with membranes from embryonic (E15-E18) or young postnatal mice. In interspecies cultures where mouse retinal fibers had to grow on chick tectal membranes, or vice versa, the same preference for anterior tectal or collicular membranes in growth of temporal retinal fibers is observed, suggesting some similarities in the cues used in both species. PMID- 2591318 TI - Systematic non-uniform distribution of parthenogenetic cells in adult mouse chimaeras. AB - Even though pure parthenogenetic mouse embryos die shortly after implantation, their cells are capable of participating in normal development of chimaeras when aggregated with fertilized embryos. Here we present data on parthenogenetic contribution to the oocyte populations measured by progeny tests in female chimaeras, and on distribution of parthenogenetic cells among the different organs by GPI typing. Systematic uneven distribution was detected. The highest level of participation was registered in the tissues of permanent cells (e.g. up to 63% in female germline). On the other hand, parthenogenetic cells were absent in several tissues that have extensive capacity for postnatal growth or selfrenewal. This finding suggests that uneven selective processes operate against parthenogenetic cells within certain differentiation pathways during fetal and postnatal life, as has already been observed in the development of extraembryonal membranes. It is likely that more than one mechanism is responsible for these selections. Parthenogenetic cells may start to differentiate in all cell lineages, but they are not able to react normally at certain points in the developmental pathway, for example to induction signals and, therefore, the cells fail to complete the normal processes of development, or to the proliferation requirement so that the fertilized counterpart gradually takes over the cell lineage. Paternally derived gene(s) might have a unique role in the development of tissues lacking parthenogenetic contribution. PMID- 2591319 TI - Cutaneous nerves of the embryonic chick wing do not develop in regions denuded of ectoderm. AB - Peripheral nerves travel to their targets along precise routes, and it is likely that different cues provide guidance at different stages of the journey. In a developing chick limb, the cutaneous nerve fibres follow at first deep mixed nerve trunks, in company with motor axons; they branch from these trunks at predictable points and approach the skin; they then ramify profusely to form a plexus at a precisely defined depth beneath the ectoderm, at exactly the same level as the blood vascular plexus. To analyse the role of signals from the target patch of skin in regulating cutaneous nerve development, we have ablated patches of dorsal wing ectoderm using short-wave ultraviolet irradiation at E4 (embryonic day 4), approximately one day before nerves grow into the limb bud. The irradiated patches remain denuded of ectoderm for more than a week, by which time the cutaneous nerve plexus on the contralateral control side is well developed and can be revealed by whole-mount silver staining. Where the ectoderm has been ablated, no cutaneous nerve plexus forms, and the nerve branches that normally would have diverged from the neighbouring mixed nerve trunk to innervate the missing patch of skin are absent - ab initio, apparently. The routes of the mixed nerve trunks are not affected. Partial ablation of the territory of a cutaneous nerve branch often leads to loss of the whole nerve branch; the intact skin territory thus left vacant is invaded by ramifications from the remaining cutaneous branches, as expected if the normal extent of a cutaneous nerve's territory is regulated by competition. Where there is an ectodermal lesion, cutaneous innervation stops precisely at its boundary, even though the vascular plexus extends for some distance beyond this margin, beneath the denuded surface. The data suggest that the embryonic skin is required firstly to trigger divergence of cutaneous nerve branches from the mixed nerve trunks, and secondly, once the nerve fibres have reached the skin, to supply a trophic cue (probably NGF) encouraging growth of a plexus; at the same time, the embryonic skin generates a signal inhibiting nerves from approaching closer than about 70 microns to the surface. PMID- 2591320 TI - Transcription of the Spec 1-like gene of Lytechinus is selectively inhibited in response to disruption of the extracellular matrix. AB - The influence of the extracellular matrix (ECM) on differential gene expression during sea urchin development was explored using cell-type-specific cDNA probes. The ECM of three species of sea urchin, Strongylocentrotus purpuratus, Lytechinus variegatus and Lytechinus pictus, was disrupted with the lathrytic agent beta aminopropionitrile (BAPN), which inhibits collagen deposition in the ECM and arrests gastrulation (Wessel & McClay, Devl Biol. 121: 149, 1987). The levels of several mRNAs (Spec 1, Spec 2, CyIIa actin, CyIIIa actin and collagen in S. purpuratus, and metallothionine, ubiquitin and LpS3 in L. pictus and L. variegatus) were compared in BAPN-treated and control embryos. These mRNAs accumulated normally during BAPN treatment, even though the embryos did not gastrulate. To determine if the expression of any gene product is sensitive to ECM disruption, a differential cDNA screen compared poly (A+) RNA from BAPN arrested and control embryos in Lytechinus. A cDNA clone was isolated from this screen that represented a 2.1 kb mRNA that did not accumulate during BAPN treatment. Removal of BAPN resulted in the accumulation of this transcript coincident with the onset of gastrulation. This cDNA clone encodes a L. variegatus homologue of LpS1, recently demonstrated to be an ancestral homologue of the aboral ectoderm-specific Spec 1-Spec 2 gene family in S. purpuratus. Nuclear run-on assays in L. pictus suggested that transcriptional activity of LpS1 was selectively inhibited by BAPN treatment. Thus, although the accumulation of many gene products occurred independently of the embryonic collagenous matrix, the accumulation of LpS1 and LvS1 appeared to be mediated by the ECM. PMID- 2591322 TI - Leukaemia in sub-Saharan Africa. PMID- 2591321 TI - Alternative splicing of fibronectin is temporally and spatially regulated in the chicken embryo. AB - The primary gene transcript for the adhesive extracellular matrix glycoprotein fibronectin (FN) is alternatively spliced in three regions (EIIIA, EIIIB and V). At least one of these regions (V) has been shown to encode cell-binding sites, suggesting that splicing represents a mechanism to create functionally different forms of FN at different times and places. In order to test this hypothesis, we have examined the extent of alternative splicing of fibronectin during embryonic development. The distribution of the different spliced forms of FN mRNA in developing chicken embryos was determined using probes specific for the spliced regions in ribonuclease protection and in situ hybridization experiments. At embryonic day 2-4 (E2-4), all three spliced regions were included wherever FN mRNA was detected. At E16, however, we found spatially distinct splicing differences within the embryo, with cell-type-specific splicing excluding EIIIA and/or EIIIB in some tissues. In contrast, we did not detect exclusion of the V region. In a more detailed developmental study of the simplest of these tissues, the chorioallantoic membrane, we found that EIIIB was preferentially excluded after the completion of growth. These results suggest that FN splicing is used during development as a mechanism to create different forms of FN within the extracellular matrix by the inclusion or exclusion of specific segments. The data are consistent with an essential role for one of these segments, EIIIB, in the migration and/or proliferation of embryonic cells prior to their terminal differentiation and also suggest possible roles for the EIIIA segment. PMID- 2591323 TI - Myelodysplastic syndromes (MDS) in Zimbabweans--preliminary observations. AB - Twenty three Zimbabwean African patients who satisfied the French-American British(FAB) diagnostic criteria for the myelodysplastic syndromes(MDS) at Godfrey Huggins School of Medicine, University of Zimbabwe, between July 1985 and June 1987 are presented. The disorders appear not to behave differently from those reported in Caucasian populations with regard to clinical and haematological features. Refractory anaemia (RA) occurred in 12 (52.2%) patients; refractory anaemia with ringed sideroblasts (RARS) in 4 (17.4%) patients; refractory anaemia with excess blasts (RAEB) in 2 (8.7%) patients; refractory anaemia with excess blasts in transformation (RAEB-T) in 3 (13.0%) patients; while chronic myelomonocytic leukaemia (CMML) was observed in 2 (8.7%) patients. In 19 cases, the disease was primary and in 4 prior exposure to myelotoxic agents resulted in secondary MDS. The clinical significance of recognising the disorders is briefly high-lighted together with our current treatment protocol. PMID- 2591324 TI - Twenty-five Zambians with leukaemias. AB - Twenty-five Zambians with leukaemias were diagnosed in three years in Ndola. Acute leukaemias were certainly under-diagnosed in children. The commonest leukaemia was chronic lymphatic leukaemia (CLL), seen in 6 males and 7 females: 3 females and 2 males were aged less than 45 years. The age and sex distribution of the leukaemias in Zambia appears to resemble those of other sub-Saharan tropical African countries. It is postulated that a retrovirus could be associated aetiologically with CLL in young adults. PMID- 2591325 TI - The role of needle aspiration cytology in the differential diagnosis of accessible paediatric tumours. AB - In the period 1985-88, 171 fine needle aspirates from paediatric patients with malignant and non-neoplastic masses were processed and evaluated in the Department of Haematology, Kenyatta National Hospital, Nairobi. Sixty-five needle aspirates had the diagnosis corroborated by histological reports. The rest had relevant clinical and laboratory information to support the cytological diagnosis. The histological diagnosis confirmed cytological diagnosis in 100% for neuroblastoma, 96% for Burkitt's lymphoma, 75% for carcinoma, 68% for sarcoma cases, 53% non-Hodgkin's lymphoma and 50% for Hodgkin's lymphoma. There were no false positives. It is therefore concluded that fine needle aspiration is a useful tool. It may obviate diagnostic surgery, help in planning the course of management of patients and it is diagnostic in Burkitt's lymphoma and neuroblastoma. Fine needle aspiration cytology is an easy, cheap and quick investigation compared to surgical biopsy. PMID- 2591326 TI - Epidemiology of leishmaniases in Kenya: V. Wider search for breeding habitats of phlebotomine sandflies in three kala-azar endemic foci. AB - Intensive investigations on the breeding sites of phebotomine sandflies were undertaken in Kitui, Machakos and Baringo foci of leishmaniases in Kenya. A total of 473 soil samples weighing approximately 4,244 kg were collected from termite hills, animal burrows, tree hole, human dwellings, animal enclosures, under tree canopy, open ground, chicken coop and rock crevices habitats and incubated in the field laboratories. 267 samples weighing approximately 3002 kg were positive, producing 6419 sandflies comprising 17 different species. This study resulted in the identification of both perennial and seasonal breeding sites of most of the phlebotomine sandfly species found in these three leishmaniases foci. PMID- 2591327 TI - A clinical study of stroke. AB - The records of 99 Saudis (68 males and 31 females) admitted to the King Fahd Hospital of the University (KFHU) over a two-year period were reviewed. There was a male to female ratio of 2.2:1. Eighty-five (86%) patients were above 44 years old. All the patients under 44 years old were males. The major predisposing factors identified were hypertension (65%), diabetes mellitus (36%), cardiac disease (20%) and cigarette smoking (29%). The combination of hypertension and diabetes mellitus seemed to carry a higher risk especially in women. Motor dysfunction, encountered in 95 (96%) patients was the dominant clinical feature, and presented mainly as hemiparesis (83 out of 95). Impaired level of consciousness at presentation carried a poor prognosis particularly in the elderly. PMID- 2591329 TI - An improved kit for culturing clean nematode, larvae from faeces. AB - A kit for rapid recovery of clean hookworm and Strongyloides stercoralis larvae from faeces was devised. It consists of a 2.0dl perspex cup shaped container 35 x 30 x 24mm in size. A horse shoe stirrup aluminium sheet 54mm long and 20mm wide is inserted into the container so that the free ends stand at the bottom of the apparatus. The back of the stirrup carries a plastic disc 30mm in diameter through which two adjacent crescent shaped openings are cut. A strip of filter paper 40 x 20mm in size passes through the crescent openings astride the stirrup and its loose ends are bound together by means of a stapler. When the kit is assembled, the disk fits firmly in the middle of the container dividing it into lower and upper chambers. The staples free ends of the filter paper hang immersed into water in the lower chamber of the apparatus. A faecal sample is smeared on the upper part of the filter paper. Nematode larvae, if present, crawl from the faeces down the damp filter paper into the water at the bottom of the container. PMID- 2591328 TI - A study of the efficacy and safety of albendazole (Zentel) in the treatment of intestinal helmenthiasis in Kenyan children less than 2 years of age. AB - One hundred children comprising of 57 males and 43 females aged between 8 and 24 months entered the study. 46 children had single and 54 children had multiple helminth infections. All children received albendazole 200 mg (10 ml) suspension as a single dose. Albendazole proved very effective and safe in the treatment of single and multiple helminth infections in children under 2 years of age, achieving cure rates of 100% in both Ascaris lumbricoides and Necator americanus respectively, 83% in Trichuris trichiura and 66% in Hymenolepis nana. Treatment of polyparasitism appears to be of benefit in improving nutritional status using haemoglobin concentrations as an index. PMID- 2591330 TI - The use of flunitrazepam (Rohypnol) in paediatric plastic surgery. AB - The efficacy of flunitrazepam, a sedative and hypnotic agent, in facilitating minor procedures in plastic surgery was assessed in 25 children. The drug was administered in a dose of 0.030 mg/kg body weight. Adequate sedation was achieved with minimal side effects. The respiratory rate and the blood pressure showed minimal change whereas the pulse rate was unaltered. PMID- 2591331 TI - Radiological pattern of chest disease in a provincial hospital. AB - Chest x-rays of 533 patients were prospectively studied over a period of 6 months. The sex, age and disease types were recorded. The sex ratio was found to be variable according to the disease. About one third of the patients were under 10 years of age. 83% of the total were in the age range 0 to 49 years. 41 per cent of the cases had lung infection; pulmonary tuberculosis accounting for one fourth of these. Cardiac lesions constituted 11%. Other chest diseases accounted for 7%. 27 percent of the chest x-rays were reported as normal. PMID- 2591333 TI - Idiopathic peripheral gangrene: a case report and literature review. AB - An 11-month old male infant presented with dry idiopathic peripheral gangrene (IPG) of both feet. Subsequently spontaneous autoamputation occurred and the stump healed. Including this patient, 8 cases of IPG under 12 years of age seen at the Kenyatta National Hospital between 1978 and 1986 were analysed. 5 were males and 3 were females. All the 8 children except one had an illness preceding IPG. The literature is reviewed and the management is discussed. PMID- 2591332 TI - The amino acid and fatty acid composition of the thermostable lipoprotein ("Antigen 880") of hydatid cyst fluid (HCF). AB - Analysis for the amino acid composition of "Antigen 880" was carried out by use of double dimension paper chromatography and Biotronik 2,000 automatic amino acid analyzer. By the double dimension paper chromatography, leucine, phenylalanine, tyrosine and alanine were identified as amino acid components of the protein moiety of "Antigen 880". In the Biotronik 2,000 automatic amino acid analyzer showed the concentration of the various amino acids to be as follows: isoleucine, leucine, tyrosine, phenylalanine, lysine and histidine were identified as amino acid constituents of "Antigen 880". Quantitative studies in Biotronik 2,000 analyzer showed the concentration of the various amino acids to be as follows: valine -0.85 mumol/ml; leucine - 0.22 mumol/ml. /ml; iso-leucine - 0.18 mumol/ml; tyrosine - 0.04 mumol/ml, and histidine - 0.02 mumol/ml. The fatty acid composition of the lipid moiety of "Antigen 880" was investigated by use of Gas Liquid chromatography. In this method, C8:0. C10:0, C12:0, C14:0, C16:0 and C18 were identified as the fatty acid constituents of the lipid moiety of "Antigen 880". PMID- 2591334 TI - Suicide and sermon reference in schizophrenia--a case report. AB - A case of a 28-year old married Nigerian woman who castrated in response to a sermon reference is presented. Possible import of psychological and socio cultural influences are discussed. Drawbacks in the effective management of such patients are highlighted. PMID- 2591335 TI - Intraventricular haemorrhage and the renin-angiotensin-aldosterone system in very low birthweight infants. AB - Blood volume, plasma renin activity (PRA) and urine aldosterone excretion (UAE) were measured in ten very low birthweight infants who had a Grade 3 or 4 intraventricular haemorrhage (IVH) during the first 2 days after birth. Mean (range) birthweight was 950 (630-1500) g and gestational age was 27 (23-31) weeks. Nine infants were receiving assisted ventilation and one was breathing spontaneously. Eight IVH occurred on the first postnatal day and two on the second; seven were symptomatic and three asymptomatic. PRA was significantly higher than control values on Day 1 only; median 244 (range 91-654) ng/ml per h vs. 64 (4-259) ng/ml per h (P less than 0.01). Infants with symptomatic IVH in the preceding 8 h (n = 6) all had PRA greater than 300 ng/ml per h; none of these infants had received transfusions or volume expansion between IVH and PRA measurement. PRA was less than 100 ng/ml per h in the three infants with asymptomatic IVH and one infant with greater than 24 h interval between IVH and PRA measurement; three of these four had received transfusions prior to PRA measurement. UAE was not significantly different from control values on either Day 1 or Day 2. Blood volume at 22 +/- 3 h postnatal age ranged from 75 to 107 ml/kg. There was an inverse logarithmic correlation between PRA and blood volume (r = 0.883; P less than 0.005), with PRA values exceeding 300 ng/ml per h when blood volume was less than 90 ml/kg. UAE did not correlate with either PRA or blood volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591336 TI - Premature membrane rupture in pregnancies of less than 34 weeks gestation. AB - The outcome of pregnancies complicated by premature membrane rupture (PROM) at gestations of less than 34 weeks during a one-year period was reviewed. At presentation, infection was suspected in 12 of the 56 mothers, but confirmed in only three. All non-infected patients were then admitted to the ward and managed expectantly. Despite membrane rupture of up to 3-weeks duration, there were no episodes of proven maternal infection amongst the inpatients. Following delivery, seven babies had positive blood cultures; antenatal infection had been suspected, but not proven, in one case only. Four mothers developed postpartum infection which responded to antibiotic therapy. All mothers with infection, presenting either antenatally or postnatally, delivered within 48 h of membrane rupture and in all infected neonates the duration of membrane rupture was 72 h or less. The occurrence of sepsis was not related to the gestational age at onset of the membrane rupture. We conclude that patients with rupture of the membranes of 72 h duration or longer may be admitted for expectant management, even if presenting early in the second trimester, without an increased risk of infection. PMID- 2591337 TI - Quetelet's index as a measure of body fatness in young infants. AB - There is a dearth of body composition techniques suitable for use in young infants. We have investigated the ability of Quetelet's index (W/H2) to predict body fatness in a group of male and female infants at 5 and 11 weeks of age. Fat free mass and hence fat mass was determined using an H2 18O dilution technique. FM/H2 and Quetelet's index were significantly correlated in all but the male, 11 week old infants. However Quetelet's index could not be used in a predictive capacity because of the poor variation accounted for by the relationships. It is possible that Quetelet's index is a poor method of predicting body fatness in young infants because of the very rapid changes that are occurring in body weight and length at that time. PMID- 2591338 TI - Developmental changes of plasma ganglioside concentration during the neonatal period. AB - We investigated the developmental changes of plasma ganglioside concentration during the neonatal period. The mean plasma ganglioside concentration at birth was 8.22 +/- 3.70 nmol lipid-bound sialic acid (LBSA)/ml, significantly lower than the value in adults (12.05 +/- 1.36 nmol LBSA/ml, P less than 0.02). However, it increased rapidly early in the neonatal period and reached its maximum level at 14 days of age (16.25 +/- 6.04 nmol LBSA/ml), which was higher than that of adults (P less than 0.05); then it decreased slowly to the adult level at one month of age. The mean plasma ganglioside concentration in preterm infants (gestational age less than 37 weeks) was 6.65 +/- 3.35 nmol LBSA/ml, somewhat lower than that of fullterm infants (gestational age greater than or equal to 37 weeks, 9.90 +/- 3.39 nmol LBSA/ml, P less than 0.02) at birth. After birth, it increased much more rapidly in preterm infants and there was no significant difference between these two groups at 5 days of age. Plasma ganglioside concentration at birth increased gradually in correlation with gestational age. Our investigations show that plasma ganglioside concentration may reflect the development and maturation of the central nervous system to some degree, at least early in the neonatal period. PMID- 2591339 TI - Erythrocyte acid phosphatase phenotype and gestational length: no relationship in a sample of 3001 births. AB - Erythrocyte acid phosphatase (ACP1) phenotype was examined in 3001 Caucasian infants born at the University of Michigan Women's Hospital. Contrary to reports from other studies, there was no relationship between the ACP1 phenotype and risk of preterm birth in either the total sample or when the sample was subdivided by sex of infant. PMID- 2591340 TI - Respiratory modulation of heart rate in newborn infants. AB - Spectral analysis was performed on ventilation and instantaneous heart rate data recorded in 15 term infants during quiet sleep in the first week after delivery, and in 11 of these infants during active sleep. There was a close relation between the main peaks of the ventilation spectra and the corresponding histograms of the reciprocals of Ttot. The spectra for instantaneous heart rate showed power at the rate of breathing (HF) and also at lower frequencies, 0.04 0.2 Hz (LF). During quiet sleep, the relative magnitudes of the HF and LF peaks for heart rate were found to depend on the respiratory rate and the variability of Ttot. During active sleep, most of the power in the heart rate spectrum was concentrated in the LF region. Weighted coherences between ventilation and heart rate were higher during quiet than active sleep, both in the HF and LF spectra. LF power was higher during active than quiet sleep in both ventilation and heart rate. The results suggest that the pattern of breathing has a marked effect on the shape of the heart rate spectrum. In most infants, however, there is no fixed phase relationship between oscillations in ventilation and heart rate, at high or low frequencies. These oscillations are affected by sleep state and hence, by implication, by central nervous system rhythm generators. PMID- 2591341 TI - [Interrelations of inhibition and anxiety]. AB - Normal anxiety and inhibition play a role in the development and the structuration of the personality, and in processes of adaptation to the environment. Pathological anxiety and inhibition are expressed by different symptoms, closely associated, essentially during reactional and neurotic troubles, which are denominated "anxiety disorders" in the DSM-III. Their interrelations are important, whatever the etiological approach would be: - between inhibition, symptoms and anxiety, as far as the psychodynamic approach is concerned; --between the awakening process and the ability to delay with a behavioral point of view; --between biochemical modifications, essentially of 5 hydroxy-tryptamine and other neurotransmitters, as far as the biological approach is concerned. PMID- 2591342 TI - Extent of resection in temporal lobectomy for epilepsy. I. Interobserver analysis and correlation with seizure outcome. AB - The extent of resection was assessed in 45 temporal lobectomies for medically intractable epilepsy with mapped temporal lobe foci. Postoperative magnetic resonance imaging (MRI) in the coronal plane was used to quantify the extent of resection of superior lateral, inferior lateral, basal, and medial structures, including the amygdalohippocampal complex. A new 20-compartment model of the temporal lobe was used for this assessment. Blinded interobserver variability was minimal. Intraoperative measurements and maps routinely overestimated the actual extent of resection, especially of medial structures. One year after surgery, 70% of patients remained seizure-free (except for auras). Seizure-free outcome was accomplished despite varying degrees of resection, but was more likely achieved with more extensive resections in all compartments. Among patients with mesiobasal foci, seizure-free outcome correlated significantly with extent of resection of amygdalohippocampal complex. We conclude that assessment of extent of resection by postoperative MRI provides an objective basis of evaluating outcome after temporal lobectomy. It allows a rational approach to understanding of operative failures and is potentially useful in comparing efficacy of various surgical approaches. PMID- 2591343 TI - Extent of resection in temporal lobectomy for epilepsy. II. Memory changes and neurologic complications. AB - We present correlations of extent of temporal lobectomy for intractable epilepsy with postoperative memory changes (20 cases) and abnormalities of visual field and neurologic examination (45 cases). Postoperative magnetic resonance imaging (MRI) in the coronal plane was used to quantify anteroposterior extent of resection of various quadrants of the temporal lobe, using a 20-compartment model of that structure. The Wechsler Memory Scale-Revised (WMS-R) was administered preoperatively and postoperatively. Postoperative decrease in percentage of retention of verbal material correlated with extent of medial resection of left temporal lobe, whereas decrease in percentage of retention of visual material correlated with extent of medial resection of right temporal lobe. These correlations approached but did not reach statistical significance. Extent of resection correlated significantly with the presence of visual field defect on perimetry testing but not with severity, denseness, or congruity of the defect. There was no correlation between postoperative dysphasia and extent of resection in any quadrant. Assessment of extent of resection after temporal lobectomy allows a rational interpretation of postoperative neurologic deficits in light of functional anatomy of the temporal lobe. PMID- 2591344 TI - Modulation of generalized spike-and-wave discharges during sleep by cyclic alternating pattern. AB - Because arousal plays a critical role in activation of epileptic phenomena, we analyzed the behavior of interictal generalized spike-and-waves (S-W) during the two recently identified modalities of arousal control during NREM sleep: (a) the cyclic alternating pattern (CAP), expressed by successive biphasic (phase A and phase B) fluctuations of arousal; and (b) non-CAP (NCAP), characterized by prolonged stable periods of EEG and arousal level. Within the single NREM stages, phase A consists of clusters of phasic events associated with transient arousal activation, whereas phase B is represented by the periodic reappearance of the EEG background and reflects a rebound inhibitory condition. The polysomnograms of 10 subjects with a wide age range and affected by primary generalized epilepsy displayed significant differences (all at p less than 0.01) between the spike indexes (S-W/min) of CAP (2.9) and NCAP (1.3), of phase A (7.4) and phase B (0.3), and of NCAP and phase B. For distribution of S-W, a significant prevalence of EEG paroxysms was detected during CAP as compared with NCAP (68 vs. 32%, p less than 0.001), and 93% of all the interictal bursts that occurred in CAP occurred in phase A (p less than 0.001). Our data stress the arousal-dependent influence of CAP and NCAP on modulation of generalized epileptic mechanisms during sleep. PMID- 2591345 TI - Ictal characteristics of cryptogenic partial epilepsies in infancy. AB - Twenty-three patients with onset of partial seizures (PS) during the first 2 years of life were collected in a single neuropediatric center and ictal events were analyzed. All patients initially had normal developmental and neurologic examinations, negative etiologic investigations, and at least two nonfebrile PS of a single type. Mean follow-up from first seizure to the last contact with the patient was 51 months (SEM 8.17 months). Ictal semiology was characterized by three types of seizures: simple PS with motor signs, complex partial seizures (CPS) with impairment of consciousness at onset followed by motor manifestations, and CPS with motor activity at onset. Versive phenomena, oroalimentary automatisms, and vegetative manifestations were frequently associated. The topography of the ictal discharges and the elementary ictal events, suggested involvement of the temporal lobe and somatomotor area. The diagnosis of PS can be difficult during the first year of life since some patients beginning with generalized seizures may evolve into partial seizures. The prognosis is guarded with regard to seizure persistence, but the neurologic outcome is better as a whole than is reported for infancy-onset epilepsies. PMID- 2591346 TI - Hemimegalencephaly and intractable epilepsy: benefits of hemispherectomy. AB - We observed 4 children with hemimegalencephaly, (3 boys, 1 girl aged 3-7 years). One child had a linear sebaceous nevus. All patients had a similar clinical, EEG, and neuroradiologic pattern. All patients had macrocrania, hemiparesis, hemianopsia, and psychomotor retardation of variable degree. All cases had an epileptic syndrome with onset during the first days or the first months of life. The seizures were consistently similar: partial motor seizures, generally hemiclonic and asymmetric brief tonic seizures, in series, involving predominantly one side of the body, contralateral to the cerebral damage. The EEG was initially characterized by a hemihypsarrhythmia and afterward, over the malformed hemisphere, by a rather high-frequency background activity associated with almost continuous transients of spikes, sharp waves, and spike and waves that progressively involved the contralateral hemisphere. Hemispherectomy was performed in two children with sudden and complete recovery from seizures and improvement in psychomotor development. Macroscopic examination was consistent with the computed tomography (CT) scan and magnetic resonance imaging (MRI) showing pachygyria and poorly represented white matter. Histologic examination showed the characteristic absence of cortical neuronal layering, and the presence of giant neurons, neuronal heterotopias, and gliosis. For hemispherectomy to be successful, we believe prolonged EEG monitoring is needed to verify that no seizures are originating in the normal hemisphere. PMID- 2591347 TI - Photolysis of the lysosomal neuraminidase in cultured human skin fibroblasts in the presence of a photoreactive competitive inhibitor. AB - Photolysis of the lysosomal neuraminidase in crude homogenates of cultured human skin fibroblasts was carried out using the potent competitive enzyme inhibitor, 9 S-(4-azido-2-nitrophenyl)-5-acetamido-2,6-anhydro-2,3,5,9-tetradeoxy-9 -thio-D - glycero-D-galacto-non-2-enonic acid (9-PANP-2,3-D-NANA). Irradiation of the homogenate and the inhibitor (2 min, pH 4.3, 10 degrees C) with a medium pressure mercury lamp resulted in about a 24% reduction of enzyme activity compared to irradiated controls that did not contain additives. No significant loss of activity was observed with homogenate that contained a photoreactive thioglycoside of sialic acid that was not an inhibitor of the enzyme. Similarly, the enzyme activity was not affected when 2-deoxy-2,3-dehydro-N-acetyl neuraminic acid was photolyzed with the homogenate. The latter is a potent competitive inhibitor but it is not photoreactive. Also, the products obtained by prephotolyzing 9-PANP-2,3-D-NANA gave similar enzyme levels under standard assay conditions when compared with the nonirradiated material. Together, these results demonstrate that the photoinactivation is highly specific and both the aryl azide and the unsaturated pyran portion of the molecule are required for inactivation. The title compound may be useful as a potential photolabeling reagent which may facilitate purification of the enzyme and permit further characterization of the mutation in sialidosis patients. PMID- 2591349 TI - Effects of methimazole on the 5'-monodeiodinase activities of various tissues. AB - Iodothyronine 5'-deiodinases were assayed in preparations of liver, cerebral cortex and brown adipose tissue. Rate profiles at various pH values revealed that methimazole activates the liver enzyme (type I) and inhibits the enzyme from brown adipose tissue (type II). Other results show that the type II enzyme may be activated by methimazole when the concentration of endogenous sulfhydryl cofactor or of dithiothreitol in the system is low. Collectively, these results suggest an interplay between the sulfhydryl (-SH) tautomer of methimazole and the sulfhydryl activators of the enzymes. PMID- 2591348 TI - Pyrene-methyl lauryl ester, a new fluorescent substrate for lipases: use for diagnosis of acid lipase deficiency in Wolman's and cholesteryl ester storage diseases. AB - Fluorescent pyrene-methyl lauryl ester (PMLes) was synthesized and used for the determination of cellular lipase activities in lymphoblasts and fibroblasts from normal subjects and from patients affected with Wolman's or cholesteryl ester storage diseases (both exhibiting a deficiency of the lysosomal acid lipase). The hydrolysis of PMLes by acid lipase could be followed directly in a spectrofluorometer; this was possible because of the very high fluorescence emission of pyrene-methanol at 378 nm (monomeric form) in aqueous medium, whereas the substrate has practically no monomeric emission at 378 nm but emits only at 475 nm (excimeric form) in the experimental conditions used: this property permitted us to use PMLes as a fluorogenic substrate. In an alternative procedure, the enzymatic reaction could be determined after partition of the reaction mixture in a biphasic system of heptane and aqueous ethanol; the residual undegraded substrate partitioned into the upper heptane phase and the fluorescence of the product (i.e. pyrene-methanol) was read in the lower aqueous ethanolic phase, at 378 nm. PMLes was hydrolyzed in extracts of normal lymphoblasts and fibroblasts by at least two lipases, one acidic lipase (pH 4.0) and a second more neutral enzyme (pH 6.5). The acidic lipase activity was practically absent in lymphoblasts and fibroblasts from Wolman's or cholesteryl ester storage diseases. This demonstrates that the fluorescent PMLes is hydrolyzed by the lysosomal acid lipase and can be used as a very sensitive fluorogenic substrate which permits direct recording of product formation and is suitable for the enzymatic diagnosis of either of these diseases. PMID- 2591350 TI - Urinary elastase 1 in chronic pancreatic disease. AB - Serum and urine elastase 1, its renal output and clearance and urinary gamma glutamyltransferase and ribonuclease excretions were measured in 16 patients with pancreatic cancer, 23 with chronic pancreatitis and in 22 healthy controls in order to evaluate elastase 1 plasma-urine transfer in chronic pancreatic disease and to investigate any factors that might influence the clearance of this enzyme. In an additional group of 17 patients with different pancreatic diseases the serum molecular size distribution of elastase 1 after chromatography was ascertained. An increased urinary elastase 1 output was found in 4/16 patients with pancreatic cancer and in 6/23 with chronic pancreatitis. No correlation was found between circulating elastase 1 and its urinary output; a negative correlation was detected between the serum levels of this enzyme and its clearance. The excretion of ribonuclease and gamma-glutamyltransferase was correlated with elastase 1 output and clearance. While the majority of elastase 1 in serum was accounted for by high molecular forms, probably the expression of complexes with serum inhibitors, free circulating enzyme was present in all patients with high serum elastase 1. Our findings suggest that elastase 1 urinary excretion increases in some patients with chronic pancreatic disease regardless of the neoplastic or inflammatory nature of the illness. Although the availability of different amounts of ultrafiltrable enzyme may play a role in influencing elastase 1 plasma-urine transfer, renal tubular damage appears to be the most important factor influencing the increase in the urinary output of elastase 1. PMID- 2591351 TI - Factors affecting the binding of glucosylceramidase to its natural substrate dispersion. AB - This paper reports the results of ultracentrifugation experiments devised for investigating the interactions occurring in the conditions of the enzymatic assay between glucosylceramidase and the components of the substrate dispersion. This dispersion contains, besides glucosylceramide, taurocholate and oleic acid. It has been found that glucosylceramide aggregates with oleic acid, while taurocholate is unable to associate with the sphingolipid, but improves the stability of the dispersion. When a crude glucosylceramidase placental preparation is incubated with the assay mixture the enzyme is almost totally bound to the glucosylceramide-oleic acid particles. The binding between glucosylceramidase and the substrate-containing particles is dramatically depressed by changes of experimental conditions which negatively influence also the enzyme activity such as: (1) a decrease in the molarity of the citrate/phosphate buffer; (2) an increase of the buffer pH, and (3) an increase of the taurocholate concentration. An excess of oleic acid neither inhibits the binding nor the activity. These results strongly suggest that glucosylceramidase activity is directly correlated with the binding of the enzyme to the lipid interface of the substrate-containing particles. We conclude that the enzymatic mechanism of glucosylceramide hydrolysis involves at least two steps: first the physical localization of the enzyme at the lipid-water interface, second the hydrolysis of the substrate glucosidic bond. PMID- 2591352 TI - Automated conductimetric assay of human serum cholinesterase activity. AB - Serum cholinesterase activity was determined by conductimetry using samples in the microliter range. Butyrylcholine iodide was demonstrated to be a convenient substrate for the conductimetric assay. Validation of the microassay was made by using either purified enzyme or control serum. In the range of 0-60 U/l, a linear relationship was demonstrated. Correlation with a reference spectrophotometric method was obtained with a slope of 1.18. An explanation of this value is proposed, as different hydrolysis rates were obtained with human sera, depending on the substrate used (butyrylthio- or butyryl-choline ester). PMID- 2591353 TI - The arterial supply of the navicular bone in the normal horse. AB - An arteriographic and histological study of the arterial blood supply of 35 navicular bones, from 19 adult horses with no clinical or radiographical signs of navicular disease, is described. The arteries enter the navicular bone from four directions: distal, proximal, medial, and lateral. The navicular bone can be divided into areas which receive arteries from one, two, or three directions, whereas the distal supply covers the largest part of the navicular bone. The distal arteries enter the navicular bone through the nutrient foramen which contains loose connective tissue, nutrient vessels and myelinated nerves. At least 77 per cent of the nutrient foramina contains synovial membrane. Twelve per cent of the arteries in the navicular bone show histological changes. Thickening of the intima with or without splitting of the internal elastic membrane and hyalinization, fibrosis and hypertrophy of the media were observed. PMID- 2591354 TI - Development of the navicular bone in foetal and young horses, including the arterial supply. AB - A macroscopic, arteriographic and histological study of the development and the arterial anatomy of the navicular bone of 33 foetuses and 55 young horses is described. After 125 days of gestation the blood supply consists of two routes: one situated in the superficial layer of the fibrocartilage and the other similar to the blood supply of the navicular bone of the normal mature horse. After 270 days gestation, the blood vessels in the fibrocartilage gradually regressed and retracted until they have disappeared at six months after birth. At two months after birth the first macroscopic thinning of the fibrocartilage was noticed. From seven months to one year about 45 per cent of the navicular bones showed a slight thinning of the fibrocartilage. A positive correlation was found between radiographic abnormalities (ie enlargement of the nutrient foramina) and the frequency of thinning of the fibrocartilage. Radiographic abnormalities were first recognised 14 days after birth, whereas the arteriogram showed the first changes such as fewer or no arteries entering distally at the distal extremities at 10 weeks after birth. At four weeks after birth the first arterial wall changes were found, ie intimal thickening with or without splitting of the internal elastic membrane. From that age onward, the number of navicular bones with arterial wall changes gradually increased. Starting at five months after birth only 6 to 20 per cent of the arteries in the navicular bones without radiographic abnormalities showed arterial wall changes. However, the navicular bones with radiographic abnormalities showed arterial wall changes in 25 to 80 per cent of the arteries. PMID- 2591355 TI - The effect of unilateral resection of segments of both palmar digital arteries on the navicular bone in ponies: an experimental study. AB - Clinical, radiographical, scintigraphical and histological effects on the navicular bone after resection of the medial and lateral palmar digital arteries in the pastern of one forelimb in ponies are evaluated. The acute disruption of the main blood supply of the distal extremity causes lameness due to the suddenness of the resection in which the collateral circulation is insufficiently developed. Because of the compensatory collateral circulation, no permanent symptoms of ischaemia occur despite the partial resection of both palmar digital arteries. Histologically the percentage of relative osteoid volume of the operated limb was significantly higher than in the control limb. PMID- 2591356 TI - The arterial supply of the navicular bone in adult horses with navicular disease. AB - A macroscopical, arteriographical and histological study was made of the arterial supply of the navicular bones of horses with clinical and/or radiographic signs of navicular disease. Based on the clinical and radiological findings the navicular bones of 40 Warmblood horses are divided into four different groups. In the pattern of the arteriogram obvious changes are noticed: an imbalance and a distal to proximal shift between the distal and proximal arterial supply occur, indicating a reduction of the distal blood supply with a compensatory reaction of the proximal, medial and lateral supply. The changes in the pattern of the arteriogram are histologically defined by arterio(lo) sclerosis and newly formed arteries. The presence of radiologically visible nutrient foramina is associated with a changed pattern in the arteriogram, increased bone remodelling and fibrosis. Ischaemia and increased pressure (hypertension and/or increased intra articular pressure) are considered to be responsible for changes in form and number of radiologically visible nutrient foramina. PMID- 2591357 TI - The effect of artificial occlusion of the Ramus navicularis and its branching arteries on the navicular bone in horses: an experimental study. AB - The clinical, radiographic, arteriographic, scintigraphic and histological effects of experimental occlusion of the Ramus navicularis (R. Navicularis) and its branching arteries are evaluated. Occlusion of the R. navicularis and its branching arteries creates changes, arteriographically and histologically, which resemble those of navicular disease. The increased bone remodelling, the shift in arterial pattern, the formation of collaterals and the increased connective tissue in the synovial membrane and nutrient foramina, as a reaction to the reduction of the distal arterial supply of the navicular bone, are also pathological features in the navicular bones of horses with navicular disease. The results of the present study support the theory that a reduced distal arterial supply of the navicular bone is important in the pathogenesis of navicular disease. PMID- 2591358 TI - Navicular bone disease: a comparative histomorphometric study. AB - Twelve horses suffering from navicular bone disease were examined in a prospective, controlled histomorphometric study for six months. The objective was to compare the histology of navicular bones from untreated animals to those treated with the egg-bar shoeing technique. These data were compared to similar sections from three normal animals. The current investigation provided quantitative support to previous findings concerning clinical improvement. Detailed histology, changes in bone morphometry and pathophysiological reactions are discussed. PMID- 2591359 TI - Laryngotracheal lesions following routine orotracheal intubation in the horse. AB - Sequelae of routine orotracheal intubation under clinical conditions were characterised in 38 healthy horses presented at three veterinary medical teaching hospitals. Four of these were necropsied and their tissues studied histologically. To minimise variation, 30 mm id cuffed silicone endotracheal tubes or Cole cuffless tubes were used in all patients. Fibreoptic endoscopic examination of upper respiratory and tracheal areas was accomplished pre intubation, immediately post extubation and after 24 h. Endoscopy revealed that intubation was associated with laryngeal and/or tracheal lesions in all horses. Observations included abundant tracheal mucus, epithelial ecchymoses, basement membrane haemorrhage and mucus covered diphtheritic membrane plaques. Histological examination of lesions from the upper respiratory system of the four necropsied horses confirmed that the damage was comparable to that associated with tracheal intubation and reported in other species. PMID- 2591360 TI - Further experiences with non-surgical correction of nephrosplenic entrapment of the left colon in the horse. AB - Non-surgical correction of nephrosplenic entrapment of the left colon was attempted in 27 cases. In two cases the method failed and a laparotomy was necessary. Two other horses had a recurrence, one of which underwent laparotomy because of torsion of the caecal body. PMID- 2591361 TI - Changes in circulating equine erythrocytes induced by brief, high-speed exercise. AB - Five horses were exercised at 10m/sec at a 3 degree incline for 2 mins. Packed cell volume, erythrocyte count, haemoglobin concentration, mean corpuscular volume, plasma protein, total white cell count and lymphocytes increased significantly in blood samples taken after exercise, compared with those taken before exercise; but mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration decreased. Erythrocytes were more resistant to osmotic stress after exercise, but their shape and degree of deformity were unaffected by exercise. PMID- 2591362 TI - Induction of peritoneal adhesions with small intestinal ischaemia and distention in the foal. AB - Twenty-two foals were divided into groups of intestinal distension and intestinal ischaemia as methods to induce peritoneal adhesions. In the first group, the lumen of a segment of distal small intestine was occluded without extramural vascular compromise and distended with lactated Ringer's solution to a constant pressure of 25 cm H2O for 2 h within the abdomen. The ischaemic group underwent 70 mins total vascular occlusion of identical segments of bowel. Serosal biopsies were obtained before and after each experimental procedure and following 60 mins of reperfusion. Similar biopsies were harvested from a control group of foals with no bowel occlusions. The foals were destroyed 10 days after surgery and tissues collected for histological and ultrastructural evaluation. Experimental and control mesothelial surfaces were denuded histologically immediately after experimental occlusions. Serosal oedema and cellular infiltration were observed following reperfusion of the ischaemic segments but were present immediately after 2 h of distension. All foals had developed bowel-to-bowel and bowel-to mesentery adhesions of the experimental segments. Control foals under 30 days old exhibited mesenteric contraction and thickening of the isolated segment whereas those older than 30 days had little or no mesenteric thickening or contraction. Histologically, in the experimental segments, fibrous tissue had formed on the outer boundary of the original serosa, and new mesothelial-like cells were present on the surface of fibrous tissue in some areas. Some serosal fibrosis was also seen in most of the control segments. PMID- 2591364 TI - Successful choledocholithotomy in a horse. PMID- 2591363 TI - Subcutaneous rupture of the urachus, its diagnosis and surgical management in three foals. PMID- 2591365 TI - [Acute aortic dissection: clinical aspects--diagnosis--therapy--follow-up]. PMID- 2591366 TI - Imaging of viroids in nuclei from tomato leaf tissue by in situ hybridization and confocal laser scanning microscopy. AB - The intracellular localization of viroids has been investigated by viroid specific in situ hybridization and analysis by digital microscopy of the distribution of the fluorescent hybridization signals. Isolated nuclei from green leaf tissue of tomato plants infected with potato spindle tuber viroid (PSTVd) were bound to microscope slides, fixed with formaldehyde and hybridized with biotinylated transcripts of cloned PSTVd cDNA. The bound probe was detected with lissamine--rhodamine conjugated streptavidin. Nucleoli were identified by immunofluorescence using the monoclonal antibody Bv96 and a secondary FITC conjugated antibody. In plants infected with either a lethal or an intermediate PSTVd strain, the highest intensity of fluorescence that arose from hybridization with the probe specific for the viroid (+)strand was found in the nucleoli, confirming results of previous fractionation studies. A similar distribution was found for (-)strand replication intermediates of PSTVd using specific (+)strand transcripts as hybridization probes. In order to determine if viroids are located at the surface or in the interior of the nucleoli, the distribution of the fluorescence hybridization signals was studied with a confocal laser scanning microscope (CLSM). It was shown by three-dimensional reconstruction that viroids are neither restricted to the surface of the nucleoli nor to a peripheral zone, but are instead homogeneously distributed throughout the nucleolus. The functional implications of the intranucleolar location of viroids and their replication intermediates are discussed with respect to proposed mechanisms of viroid replication and pathogenesis. PMID- 2591367 TI - Primary structure of sensory rhodopsin I, a prokaryotic photoreceptor. AB - The gene coding for sensory rhodopsin I (SR-I) has been identified in a restriction fragment of genomic DNA from the Halobacterium halobium strain L33. Of the 1014 nucleotides whose sequence was determined, 720 belong to the structural gene of SR-I. In the 5' non-coding region two putative promoter elements and a ribosomal binding site have been identified. The 3' flanking region bears a potential terminator structure. The SR-I protein moiety carries no signal peptide and is not processed at its N terminus. The C terminus, however, lacks the last aspartic acid residue encoded by the gene. Analysis of the primary structure of SR-I reveals no consistent homology with the eukaryotic photoreceptor rhodopsin, but 14% homology with the halobacterial ion pumps, bacteriorhodopsin (BR) and halorhodopsin (HR). Residues conserved in all three proteins are discussed with respect to their contribution to secondary structure, retinal binding and ion translocation. The aspartic acid residue which mediates in BR the reprotonation of the Schiff base (D96) is replaced in SR-I by a tyrosine (Y87). This amino acid replacement is proposed to be of crucial importance in the evolution of the slow-cycling photosensing pigment SR-I. PMID- 2591368 TI - Thymic epithelial cells induce in vitro differentiation of PRO-T lymphocyte clones into TCR alpha,beta/T3+ and TCR gamma,delta/T3+ cells. AB - PRO-T lymphocyte clones, which have the T cell receptor (TCR) alpha, beta, gamma and delta genes in germline configuration and heterogeneous T cell precursors freshly isolated from bone marrow of athymic nude mice, gave rise to single positive L3T4+ TCR alpha,beta+ and double negative (L3T4-LyT2-) TCR alpha,beta+ or TCR gamma,delta+ cells, but not to any cells expressing LyT2, when co-cultured with the thymic epithelial clone ET. The T cell progenitors were able to develop into cells expressing LyT2 only when cocultured with heterogeneous thymic epithelial cell preparations. The progeny of the induced PRO-T clones included cells bearing V beta 8, V beta 17 and V gamma 3 gene family products. The presence of cells expressing a TCR gamma, delta/T3 receptor complex in the cultures was also documented by the expression of RNA transcripts from the TCR delta and TCR gamma genes by induced PRO-T cells. The TCR/T3+ cells generated in the cultures expressed functionally competent T cell receptor complexes. Our results show that: (i) the same PRO-T clone can give rise to all major subsets of thymocytes upon interaction with the appropriate thymic epithelial cells; (ii) both TCR alpha,beta+ and TCR gamma,delta+ cells may originate from a common T cell progenitor; (iii) L3T4+ TCR alpha, beta+ and L3T4-LyT2- TCR alpha,beta+ cells do not necessarily pass through a L3T4+LyT2+ intermediate stage of development; and (iv) different types of thymic epithelial cells play an essential role in the differentiation of PRO-T cells into either L3T4+ TCR alpha,beta+ L3T4-LyT2- TCR alpha,beta+ or L3T4+LyT2+ and LyT2+ TCR alpha, beta+ cells in vitro. Finally, we have attempted to integrate our results and those of others in a suggested model of T cell development within the thymus. PMID- 2591369 TI - A 6000 kb segment of chromosome 1 is conserved in human and mouse. AB - A murine linkage map generated from analyses of 428 meiotic events in an interspecific cross and pulsed field gel electrophoresis allowed examination of the genomic organization of a 6000 kb segment of mouse and human chromosome 1. Analysis of five genes within this syntenic segment of both species revealed striking conservation of gene order, intergenic distance and, to a lesser extent, CpG dinucleotides. In the mouse, meiotic crossover events were not evenly distributed; a hot spot for meiotic recombination was coincident with a CpG island. These studies provide a practical approach to aid physical mapping of the human genome and a model for determining the molecular principles that govern meiotic recombination. In addition, these findings demonstrate profound conservation of genomic organization over mammalian evolution. PMID- 2591370 TI - Epidermal growth factor binding induces a conformational change in the external domain of its receptor. AB - To study the properties of the extracellular epidermal growth factor (EGF) binding domain of the human EGF receptor, we have infected insect cells with a suitably engineered baculovirus vector containing the cDNA encoding the entire ectodomain of the parent molecule. This resulted in a correctly folded, stable, 110 kd protein which possessed an EGF binding affinity of 200 nM. The protein was routinely purified in milligram amounts from 1 litre insect cell cultures using a series of three standard chromatographic steps. The properties of the ectodomain were studied before and after the addition of different EGF ligands, using both circular dichroism and fluorescence spectroscopic techniques. A secondary structural analysis of the far UV CD spectrum of the ectodomain indicated significant proportions of alpha-helix and beta-sheet in agreement with a published model of the EGF receptor. The ligand additions to the receptor showed differences in both the near- and far-UV CD spectra, and were similar for each ligand used, suggesting similar conformational differences between uncomplexed and complexed receptor. Steady-state fluorescence measurements indicated that the tryptophan residues present in the ectodomain are buried and that the solvent accessible tryptophans in the ligands become buried on binding the receptor. The rotational correlation times measured by fluorescence anisotropy decay for the receptor-ligand complexes were decreased from 6 to 2.5 ns in each case. This may indicate a perturbation of the tryptophan environment of the receptor on ligand binding. Ultracentrifugation studies showed that no aggregation occurred on ligand addition, so this could not explain the observed differences from CD or fluorescence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591371 TI - cDNA cloning and sequencing of the protein-tyrosine kinase substrate, ezrin, reveals homology to band 4.1. AB - Ezrin is a component of the microvilli of intestinal epithelial cells and serves as a major cytoplasmic substrate for certain protein-tyrosine kinases. We have cloned and sequenced a human ezrin cDNA and report here the entire protein sequence derived from the nucleotide sequence of the cDNA as well as from partial direct protein sequencing. The deduced protein sequence indicates that ezrin is a highly charged protein with an overall pI of 6.1 and a calculated molecular mass of 69,000. The cDNA clone was used to survey the distribution of the ezrin transcript, and the 3.2 kb ezrin mRNA was found to be expressed in the same tissues that are known to express the protein and at the same relative levels. Highest expression was found in intestine, kidney and lung. The cDNA clone hybridized to DNAs from widely divergent organisms indicating that its sequence is highly conserved throughout evolution. The amino acid sequence of ezrin revealed a high degree of similarity within its N-terminal domain to the erythrocyte cytoskeletal protein, band 4.1 and secondary structure predictions indicate that a second region of ezrin contains a long alpha-helix, a feature also common to band 4.1. The structural similarity of ezrin to band 4.1 suggests a mechanism for the observed localization to the membrane, and a role for ezrin in modulating the association of the cortical cytoskeleton with the plasma membrane. PMID- 2591373 TI - Alpha-amanitin resistant transcription of protein coding genes in insect and bloodstream form Trypanosoma brucei. AB - The variant cell surface glycoprotein (VSG) gene expression sites of the protozoan Trypanosoma brucei are transcribed by an unusual alpha-amanitin resistant RNA polymerase. All other protein coding genes of T.brucei examined to date are transcribed by an alpha-amanitin sensitive RNA polymerase, presumably RNA polymerase II. We now show that transcription of protein coding genes by alpha-amanitin resistant RNA polymerases is not unique to the bloodstream form expressed VSG gene expression sites, but also occurs in insect form trypanosomes, which do not express VSG genes. In insect form trypanosomes transcription of the procyclin or PARP genes is resistant to alpha-amanitin to a degree comparable with that of VSG and ribosomal RNA (rRNA) genes. Comparison of the alpha-amanitin resistantly transcribed PARP and VSG gene families shows that they both produce one of the most abundant mRNAs [1-3% of poly(A)+] and they both encode the major cell surface proteins of their respective life cycle stages. Transcription of a subset of functionally comparable protein coding genes is thus mediated by an RNA polymerase which differs from the regular RNA polymerase II. PMID- 2591372 TI - The ocs-element is a component of the promoters of several T-DNA and plant viral genes. AB - The ocs-element is an enhancer element first identified in the promoter of the octopine synthase gene (OCS) where it occurs as a 16 bp palindromic sequence. The transcriptional enhancing activity of the ocs-element correlated with in vitro binding of a transcription factor. We have now identified ocs-elements in the promoter regions of six other T-DNA genes involved in opine synthesis and three plant viral promoters including the 35S promoter of cauliflower mosaic virus. These elements bind the ocs transcription factor in vitro and enhance transcription in plant cells. Comparison of the sequences of these 10 elements has defined a 20 bp consensus sequence, TGACG(T/C)AAG(C/G)(G/A)(A/C)T(G/T)ACG(T/C)(A/C)(A/C), which includes the 16 bp palindrome in its central region. We propose the name ocs-element for this class of promoter elements of similar sequence and function. PMID- 2591374 TI - Supercoiled DNA is interwound in liquid crystalline solutions. AB - Two structures have been proposed for supercoiled DNA: it is idealized either as a toroidal ring or as a rod of two interwound duplex chains. The latter model is the most widely depicted but the evidence remains controversial. We have worked with monomers and dimers of two plasmids, pUC8 and pKS414, of similar size and natural superhelical density. pKS414 contains a bend promoting sequence whereas pUC8 does not. In concentrated solutions these plasmids form a partially ordered liquid crystalline phase which is found, using neutron diffraction, to consist of a hexagonally packed assembly of parallel rod-like particles. This shape strongly suggests an interwound conformation for which some structural parameters are deduced. The mass/unit length obtained by combining the area of the hexagonal lattice and the concentration is approximately 3.6 times that of linear DNA. This implies a shallow superhelical pitch angle approximately 36 degrees which, when combined with the known number of supercoil turns, yields the pitch approximately 360 A and radius approximately 80 A for the supercoil. Oriented X-ray fibre diffraction patterns at 92% relative humidity indicate a B type duplex structure. Nicked circular plasmids also form liquid crystals but their behaviour, as a function of concentration, differs from that of the superhelical plasmids. PMID- 2591376 TI - Evidence that 31P NMR is a sensitive indicator of small conformational changes in the coenzyme of aspartate aminotransferase. AB - The pH dependence of 31P-NMR spectra of pig cytosolic aspartate aminotransferase, containing either N-(5'-phosphopyridoxyl)-L-aspartate or pyridoxal 5' deoxymethylenephosphonate in place of the normal coenzyme pyridoxal 5'-phosphate, has been analysed. The chemical shifts of phosphopyridoxylaspartate and of pyridoxal 5'-deoxymethylenephosphonate model Schiff base in free solution show pK values of 6.3 and 7.4, attributable to the second deprotonation step of phosphate and phosphonate, respectively. However, these compounds behave very differently when bound to apoaspartate aminotransferase. 31P-NMR spectra of these enzyme derivatives indicate that the phosph(on)ate group remains dianionic throughout the pH range 4-8.5. A clear correlation between apparent pK values obtained from spectrophotometric titration of the coenzyme chromophore and those obtained by 31P NMR indicates that the same ionisation is being reported by both methods. The data are interpreted, on the basis of available crystallographic structures of chicken mitochondrial aspartate aminotransferase, to indicate that in each case the alteration in 31P chemical shift results from a conformational change in the coenzyme 5' side chain, in which one of the structures involves a near-eclipsed pair of bonds. Such a stressed conformation produces slight alterations in bond angles around the phosphorus atom, which in turn cause the observed change in 31P chemical shift. The evidence is taken to indicate that in this case 31P NMR is a sensitive reporter of stress in enzyme-bound pyridoxal 5'-phosphate and its derivatives. PMID- 2591375 TI - Biosynthesis of dolichol by rat liver peroxisomes. AB - The ability of peroxisomes and microsomes to synthesize dolichol from [3H]mevalonate, [3H]isopentenyl-P2 or [3H]farnesyl-P2 in vitro was investigated. It was found that isoprenoid biosynthesis also occurs in peroxisomes and that this process demonstrates properties differing from those of isoprenoid biosynthesis by microsomes. The pH optimum in peroxisomes was 8.0 and, in contrast to microsomes, the peroxisomal biosynthesis was largely insensitive to detergents. After treatment with proteolytic enzymes, microsomes lost their capacity to incorporate [3H]mevalonate into dolichol, whereas proteolysis of intact peroxisomes did not influence their corresponding rate of incorporation. The soluble content of peroxisomes was separated from the membranes and found to demonstrate half of the biosynthetic capacity of the intact organelle. Fasting and cholestyramine treatment decreased only the microsomal incorporation of [3H]mevalonate into dolichol, while treatment with clofibrate, di-2-ethylhexyl phthalate or phenobarbital increased microsomal, but decreased peroxisomal labeling. After injection of [3H]mevalonate into the portal vein of rats, high initial labeling of dolichol was recovered both in isolated microsomes and peroxisomes, whereas when [3H]glycerol was administered, peroxisomal phospholipids became labeled later than the corresponding microsomal constituents. These results support the conclusion that dolichol is synthesized both in peroxisomes and the endoplasmic reticulum, but that the biosynthetic processes at these two locations have different properties. PMID- 2591377 TI - Interaction of tRNA with the A and P sites of rabbit-liver 80S ribosomes and their 40S subunits. AB - The interaction between tRNA and rabbit liver 80S ribosomes and 40S subunits was studied using a nitrocellulose membrane filtration technique. Binding of the different tRNA forms (aminoacyl-, peptidyl- or deacylated) to poly(U)-programmed 40S subunits and 80S ribosomes was found to be a cooperative process. The association constants of AcPhe-TRNA(Phe) for the A and P sites of 80S ribosomes and the cooperativity constant were measured at different temperature and Mg2+ concentration. The AcPhe-tRNA(Phe) association constant for the P site was shown to be between 2 x 10(7) M-1 and 2 x 10(8) M-1 at 25-37 degrees C and 5-20 mM Mg2+, while the affinity for the A site was 10-100-fold lower. The cooperativity constant was shown to decrease with the increase of incubation temperature and the decrease of Mg2+ concentration. The affinity of AcPhe-tRNA(Phe) for the A site of 80S ribosomes was shown to depend upon the codon specificity of tRNA at the P site. The cooperativity of the tRNA interaction with 80S ribosomes was suggested to be mostly contributed by the association with the 40S subunit and result from the correct codon-anticodon pairing at the P site. The data presented imply a codon-anticodon interaction at the P site of eukaryotic 80S ribosomes. PMID- 2591378 TI - Microsomal delta 8,14-sterol delta 14-reductase in higher plants. Characterization and inhibition by analogues of a presumptive carbocationic intermediate of the reduction reaction. AB - An enzymatic assay for delta 8,14-sterol delta 14-reductase, an enzyme involved in sterol biosynthesis, has been developed for the first time in higher plants. The properties of the microsomal enzyme have been established with respect to cofactor requirements, kinetics and substrate specificity. This enzymatic double bound reduction is thought to proceed through an electrophilic addition mechanism, involving a C14 putative carbonium ion high-energy intermediate. Using this in vitro assay, ammonium and iminium analogues of this cationic intermediate were shown to be potent inhibitors of the reduction reaction. Thus, compounds of the N-alkyl-8-aza-4 alpha,10-dimethyl-trans-decal-3 beta-ol series strongly inhibited sterol reductase (I50 = 0.07 - 4 microM) (I50/Km = 10(-4) - 10(-3), as did the antimycotic agent 15-azasterol (I50 = 0.03 microM); all of these compounds act as reaction-intermediate analogues of the proposed C14 carbonium ion intermediate. Moreover, the in vitro inhibition of the plant sterol reductase by a series of ammonium-ion-containing fungicides was demonstrated. The relative specificity of these different series of inhibitors toward cycloeucalenol obtusifoliol isomerase, delta 8----delta 7-sterol isomerase and delta 8,14-sterol delta 14-reductase, was directly studied. PMID- 2591379 TI - 2-Aminobenzoyl-CoA monooxygenase/reductase, a novel type of flavoenzyme. Purification and some properties of the enzyme. AB - A novel aerobic mechanism of 2-aminobenzoate metabolism was proposed in a denitrifying Pseudomonas species. 2-Aminobenzoic acid is activated in a coenzyme A-ligase reaction to 2-aminobenzoyl-CoA and this intermediate is dearomatized by a unique enzyme, tentatively named 2-aminobenzoyl-CoA monooxygenase/reductase. This paper describes the purification and some molecular, kinetic and spectral properties of this flavoenzyme which catalyzes the hydroxylation and reduction of 2-aminobenzoyl-CoA to an unknown non-aromatic compound. 2-Aminobenzoyl-CoA monooxygenase/reductase was purified 25-fold to a specific activity of 25 mumol.min-1.mg-1 protein using ammonium sulfate precipitation, DEAE-cellulose anion-exchange, hydroxylapatite and Mono Q FPLC anion-exchange chromatography. Superose 6 gel filtration for estimation of molecular mass resulted in one symmetrical protein peak corresponding to a molecular mass of 170 kDa. Several experimental data suggest that the protein is probably an alpha 2 dimer; however, it may exist in three dimeric forms, alpha alpha, alpha alpha' and alpha' alpha', where alpha' may be a subunit with a different conformation. Approximately 2 mol noncovalently bound FAD/mol enzyme was found, which in the absence of O2 was reduced by NADH. The enzyme was specific for the substrates 2-aminobenzoyl-CoA (Km less than or equal to 25 microM) and O2 (Km less than or equal to 5 microM), but less specific for the reduced pyridine nucleotides NADH (Km = 42 microM) or NADPH [Km = 500 microM; Vmax (NADH)/Vmax (NADPH) = 1.7:1]. The turnover number was 4250 min-1. The enzyme also reduced N-ethylmaleimide and maleimide with NAD(P)H. The substrate, the products and the reaction stoichiometry are described in two following papers. PMID- 2591380 TI - 2-Aminobenzoyl-CoA monooxygenase/reductase, a novel type of flavoenzyme. Studies on the stoichiometry and the course of the reaction. AB - The reaction catalyzed by 2-aminobenzoyl-coenzyme-A monooxygenase/reductase from a denitrifying Pseudomonas sp. has been investigated. 2-Aminobenzoyl-CoA and 2 amino[carboxy-14C]benzoyl-CoA were synthesized enzymatically using 2-aminobenzoyl CoA synthetase from the same organism. The product was purified by chromatography and characterized by ultraviolet/visible and 1H-NMR spectroscopy. The conversion of 2-aminobenzoyl-CoA catalyzed by the monooxygenase/reductase requires NADH and oxygen, and yields at least two different products depending on the relative concentration of NADH. At [NADH] less than Km (40 microM), i.e. [NADH]/[2 aminobenzoyl-CoA] approximately 0.02-0.05, the main product is probably a hydroxylated derivative of 2-aminobenzoyl-CoA, which is characterized by an absorbance maximum around 375 nm. When [NADH]/[2-aminobenzoyl-CoA] approximately 2-5, the predominant product is a non-aromatic coenzyme A thioester (lambda max approximately 320 nm). The stoichiometry in this case is 2.1-2.4 mol NADH oxidized (mol oxygen consumed)-1 (mol 2-aminobenzoyl-CoA metabolized)-1. The product is extremely unstable in the acidic pH range and undergoes decarboxylation in a few minutes at pH less than 5. Some degree of stabilisation is obtained upon reduction with sodium borohydride, probably resulting in a further reduced non-aromatic coenzyme-A thioester. PMID- 2591381 TI - The reaction of hemin with H2O2. AB - The kinetics of formation of the dominant intermediate (CII) formed between hemin and H2O2 has been studied by the stopped-flow method. CII is preceded by a precursor (CI) for which a steady state is established at an early stage of the reaction. The formation of CI from hemin and H2O2 causes only a marginal change in the optical absorbance (A). The transition CI----CII is accompanied by a substantial decrease of A in the Soret region. Relevant rate constants (or combinations of them) and the molar absorption coefficients of the intermediates at 400 nm have been determined. The absorption spectrum of CII in the Soret region has been evaluated. Aspects of the catalysis of decomposition of H2O2 by hemin in relation to the Fe3+ ion and catalase are discussed. PMID- 2591382 TI - Primary structures of five ribosomal proteins from the archaebacterium Halobacterium marismortui and their structural relationships to eubacterial and eukaryotic ribosomal proteins. AB - The complete amino acid sequences of ribosomal proteins L9, L20, L21/22, L24 and L32 from the archaebacterium Halobacterium marismortui were determined. The comparison of the sequences of these proteins with those from other organisms revealed that proteins L21/22 and L24 are homologous to ribosomal protein Yrp29 from yeast and L19 from rat, respectively, and that H. marismortui L20 is homologous to L30 from eubacteria. H. marismortui ribosomal protein L9 showed sequence homology to both L29 from yeast and L15 from eubacteria. No homologous protein was found for H. marismortui L32. These results are discussed with respect to the phylogenetic relationship between eubacteria, archaebacteria and eukaryotes. PMID- 2591383 TI - A correlation between spin lattice relaxation time and tumor growth. PMID- 2591384 TI - Safety and toleration of the non-ionic contrast medium iopentol. An intravenous phase I trial. AB - The safety and toleration of iopentol, a new non-ionic contrast medium for intravascular use, were evaluated. In the intravenous phase I study, 24 volunteers were allocated to 3 dose groups corresponding to 0.3, 0.6 or 1.2 g I/kg body weight, respectively. Injection of saline was used as control in the highest dose group. Adverse events, hemodynamic parameters, and clinical chemical parameters in the blood and urine were recorded. No severe or unexpected adverse events occurred. All findings were transient and included a sensation of warmth, a small increase in heart rate, a dilution effect on blood parameters, and enzymuria. The deviations in clinical chemical parameters fell mostly within reference ranges and were clinically insignificant. Thus, iopentol may safely be advanced to clinical trials in patients for comparative studies. PMID- 2591385 TI - Digital chest radiography with a large image intensifier. An ROC study with an anthropomorphic phantom. AB - The diagnostic performance of two systems for chest radiography was studied. One system was based on a large image intensifier, the other was a conventional film screen system. The images from the image intensifier were studied either on a digital TV screen or on 100 mm photofluorograms. Receiver operating characteristic curve analysis was performed on images of an anthropomorphic chest phantom. Low-contrast MMAP (methyl methacrylate polymer) nodules and simulated vessels were positioned over the parenchymal and the mediastinal region of the phantom. Five observers assessed the digital monitor images, photofluorograms, and conventional full-size radiograms. The results showed a significantly superior detectability for the full-size radiograms over the digital monitor images both in the parenchyma and in the mediastinum. No significant difference was found between photofluorograms and digital images. PMID- 2591386 TI - Nonpulmonary thoracic biopsy. AB - The aim of the present paper is to distinguish between thoracic pulmonary needle biopsy--which can be carried out under fluoroscopic guidance--and thoracic extrapulmonary needle biopsy, which requires a more accurate type of guidance, such as CT. Among the 500 thoracic punctures performed during the last 5 years, we considered only 90 biopsies of mediastinal (N = 58) or thoracic wall (N = 32) masses. We have thus excluded all parenchymal lesions of the lungs. For extrapulmonary thoracic masses, CT was the method of choice for biopsy guidance which provided diagnostic evidence of small-diameter mediastinal lesions that permitted analysis of the relationship to vascular structures and performance of extrapleural needle insertion, using larger-gauge needles to ensure accurate needle placement within the lesion. In both mediastinal and thoracic wall lesions an overall accuracy rate of 84% was obtained. In no case was thoracic drainage required for treatment of the moderate degree of pneumothorax that occurred in 1% of our patient population. PMID- 2591387 TI - Use of an AAPM (American Association of Physicists in Medicine) DSA phantom in quality assurance. AB - The performance of nine DSA units installed in Finnish hospitals was evaluated by means of an AAPM DSA phantom. The spatial resolution, low-contrast performance, contrast linearity, subtraction artifacts and radiation exposure were studied. The spatial and contrast resolution agree well with those published in the literature. No serious artifacts or false recording in subtraction images were noted. PMID- 2591388 TI - Intravenous digital subtraction angiography in patients with cerebral ischaemia. Evaluation of extracranial carotid lesions. AB - Over a two-year period, 167 patients with symptoms of transient ischaemic attacks or suspected minor stroke underwent intravenous digital subtraction angiography (DSA) of the carotid arteries. There were no major complications. Ninety-six patients had abnormal angiograms, 60 normal studies, and in 11 patients (7%) the examination was not of diagnostic quality, mostly because of motion artifacts. In 86 patients no therapeutic consequences resulted from the DSA examination. Twenty six patients were referred for vascular surgery, and 34 patients had either anticoagulation or aspirin therapy. In 10 patients a primary medical cause was found for their cerebral vascular symptoms. It is concluded that intravenous DSA of the carotid arteries in patients with transient ischaemic attack is a safe, diagnostically useful procedure, that can also be used on an outpatient basis. PMID- 2591389 TI - Subtracted versus non-subtracted digital imaging in peripheral angiography. AB - Digital subtraction angiography (DSA) plays an important role in the management of vascular diseases of the lower extremities. A disadvantage is the lack of an automatically moving table top. We used a 1,024 x 1,024 matrix with a large screen intensifier system and an automated "stepping" facility. In 161 examinations of the arteries of the lower extremity digital peripheral arteriography was performed with and without the subtraction technique. We compared the influence of different iodine concentrations in DA and DSA. Peripheral DA proved to be equal to peripheral DSA in the region of the pelvis, thigh and knee, with no adequate contrasting being obtained merely in the region of the lower leg arteries in about 45%. It is necessary to use contrast medium at a concentration of 300 mg I/ml. The installation of an automated "stepping" facility reduces the amount of contrast medium needed and the exposure time. PMID- 2591390 TI - Baseline screening mammography with one versus two views. AB - Two-view baseline screening mammograms (oblique and cranial views) of 303 women recalled for further studies from among 7,245 women screened were reviewed by four experienced radiologists separately to evaluate the importance of the number of views taken for screening. As compared with the oblique view only, two views, increased the number of cancers detected and decreased the number of false positive cancer diagnoses of two radiologists, but increased that of the other two. PMID- 2591391 TI - Limitations of combined flexible sigmoidoscopy and double contrast barium enema in patients with rectal bleeding. AB - Eighty-seven outpatients with non-massive rectal bleeding or asymptomatic positive fecal occult blood were evaluated with 35 cm flexible sigmoidoscopy, double contrast barium enema (DBCE) and colonoscopy. 82% had hemorrhoids and 35% harbored colorectal neoplasia. The combination of flexible sigmoidoscopy and DCBE missed none of 7 malignant lesions. However, 36% of benign polyps greater than or equal to 1 cm and 60.25% of those less than 1 cm were not detected by this combination. The presence of hemorrhoids should not prevent a search for colon neoplasia and colonoscopy is the preferred method. PMID- 2591392 TI - Validity of a postal questionnaire with regard to the prevalence of myocardial infarction in a general population sample. AB - In order to evaluate the possibility of finding persons who have suffered a myocardial infarction (MI) by postal questionnaire, a self-administered questionnaire was sent to a random sample of 4400 men aged 45-64 years, drawn from the general population. The response rate was 95%. 176 men indicated that they had been hospitalized for MI, out of which 124 cases could be verified from medical records. Of the remaining men, 33 had evidence of cardiovascular disease (CVD) in their records but no MI, and 19 men had no evidence of CVD. The sensitivity (estimated from a subsample) was 100% and the specificity 98.7%. The predictive value was 100% for a negative response and 70.5% for a positive response. The 33 positive responders whose MI could not be verified but who had evidence of CVD had characteristics fairly similar to the responders with verified MIs. However, the 19 positive responders whose MI could not be verified and who had no evidence of CVD had characteristics that were dissimilar from the MI group as well as from the negative responders. The questionnaire thus identified all the MI cases. The need for validation can be limited to the relatively small group of positive responders. PMID- 2591393 TI - Symptoms and signs of heart failure in patients with myocardial infarction: reproducibility and relationship to chest X-ray, radionuclide ventriculography and right heart catheterization. AB - 102 patients with myocardial infarction (MI) were examined by three clinicians, who independently recorded the following symptoms and signs: dyspnoea, a displaced apex beat, S3-gallop, rales, neck vein distension, hepatomegaly, and dependent oedema. Chest X-ray, radionuclide ventriculography, and (in 40 patients) right heart catheterization were carried out immediately after the physical examination. The clinicians frequently disagreed as to the presence of physical signs of heart failure in individuals. Moreover, these signs were of limited value in identifying patients with pulmonary vascular congestion on chest X-ray, reduced left or right radionuclide ventricular ejection fractions, enlarged ventricular volumes or haemodynamic evidence of ventricular dysfunction. We conclude that clinicians frequently disagree in the recognition of physical signs of heart failure, and that these signs have an unpredictable relationship to radiographic, radionuclide and haemodynamic measures of ventricular performance in patients with MI. Nevertheless, physical signs are useful in identifying patients with high risk of cardiac death. PMID- 2591394 TI - Heart rate and metabolic response to competitive squash in veteran players: identification of risk factors for sudden cardiac death. AB - We studied 10 older males during a competitive game and the early post-exercise period to define the metabolic response to squash in veteran players. For comparison, all subjects were also studied during exhaustive treadmill exercise. Squash caused a dramatic increase in heart rate (150%), and circulating levels of noradrenaline (164%), adrenaline (93%), lactate (202%) and free fatty acids (67%). These effects were independent of haemoconcentration. The early post exercise period (5 min) was characterized by persistent elevation of plasma catecholamines, lactate, and free fatty acids, hypokalaemia and ventricular arrhythmias. The heart rate and metabolic responses to squash were similar in pattern and magnitude to those observed during treadmill exercise, highlighting the strenuous nature of squash as a recreation sport. While these changes may represent appropriate physiological adaptation to exercise in health, each has been implicated in the pathogenesis of fatal ventricular arrhythmias in subjects with ischaemic heart disease. These data support the contention that squash may be an inappropriate form of exercise for older men with coronary artery disease. PMID- 2591395 TI - Adrenergic nervous system and left ventricular mass in primary hypertension. AB - A link between the activity of the adrenergic nervous system and left ventricular hypertrophy has frequently been found in hypertensives. In 16 patients with untreated primary hypertension of mild to moderate degree, we have evaluated the possible correlations between echocardiographic left ventricular mass (LVMe) and sympathetic nervous system activity, using pressor response to exogenous noradrenaline infusion, measurement of 24-h catecholamine urinary excretion and pressure response to ergometric exercise. Pressor response to noradrenaline infusion was significantly related to echocardiographic measures of left ventricular hypertrophy (correlation coefficients were: -0.60 for LVMe; -0.51 for septal thickness (ST); -0.51 for posterior wall thickness). Left ventricular mass was also related to systolic blood pressure measured during ergometric exercise (correlation coefficients were: 0.52 with LVM index, 0.51 with LVMe and 0.61 with ST). Arterial wall hypertrophy has been identified as being responsible for the vascular hyperreactivity in hypertension. A likely explanation of our findings is that the degree of left ventricular hypertrophy is associated with the degree of structural alterations of the resistance vessels and that the vascular impairment is responsible for the increased pressure response to noradrenaline. PMID- 2591396 TI - Penicillamine-induced polymyositis with complete heart block. AB - Complete heart block with severe Adams-Stokes attacks and polymyositis was observed in a 69-year-old man following 6 weeks penicillamine treatment for suspected rheumatoid arthritis. After drug withdrawal the muscle enzymes and the cardiac rhythm gradually normalized, only leaving a right bundle branch block. Although this is the first report to show that severe cardiac damage associated with penicillamine-induced polymyositis is a potentially reversible condition, the severity of the three cases reported so far warrants close observation for cardiac involvement in patients with penicillamine-induced polymyositis. PMID- 2591397 TI - Emergency coronary angioplasty in patients with severe left ventricular dysfunction or cardiogenic shock after acute myocardial infarction. AB - Emergency percutaneous transluminal coronary angioplasty (PTCA) was performed during an acute myocardial infarction (AMI) after either systemic or intracoronary thrombolytic therapy in six patients with severe ischaemic left ventricular dysfunction or cardiogenic shock, among 37 patients (17%) who were treated with PTCA during AMI over a 13-month period. Thrombolytic therapy with streptokinase (1.5 x 10 Units) was initiated after a mean (+/- SD) time delay of 5.5 +/- 1.3 h from the onset of symptoms. The infarct-related artery was found to be occluded (TIMI grade 0-1) in three patients and partially reperfused (TIMI grade 2) in the remaining patients at baseline coronary angiography. Intracoronary administration of urokinase (100-200,000 Units) was ineffective in those patients failing systemic thrombolysis and resulted in only a slight increase of residual lumen in three patients. The coronary artery could be opened by a guidewire mechanical technique in patients with persistent coronary artery occlusion and coronary dilation could be done in all patients. The mean percentage diameter stenosis of the infarct-related vessel was reduced from 98.8 +/- 2% to 27 +/- 11% (P less than 0.005). After the procedure, left ventricular ejection fraction increased from 27 +/- 8% to 41 +/- 7% (P less than 0.02), systemic blood pressure and cardiac index increased respectively from 86 +/- 10 to 126 +/- 14 mmHg (P less than 0.005) and from 2.2 +/- 0.6 to 3.3 +/- 0.6 (P less than 0.01). Left ventricular end-diastolic pressure decreased from 26 +/- 8 to 18 +/- 3 mmHg (P less than 0.05). Severe mitral regurgitation was relieved in one patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591398 TI - Radiofrequency coagulation of ventricular myocardium: improved prediction of lesion size by monitoring catheter tip temperature. AB - To assess the importance of voltage, current, impedance and catheter tip temperature for the prediction of the size of tissue injury induced by transcatheter radiofrequency application, radiofrequency pulses (500 kHz) were delivered both in vitro and in vivo to isolated ventricular preparations and the intact canine heart, respectively. Radiofrequency coagulations were performed using unipolar electrode configuration. Besides measurements of current and voltage which were used to calculate the delivered power and tissue impedance, the catheter tip temperature was monitored during each application using specially designed 6F USCI catheters with a built-in nickel/chromium-nickel thermoelement. Lesion dimensions were measured and the correlation between lesion volume and delivered radiofrequency energy, maximum changes in catheter tip temperature and the integral of the temperature curve were calculated. First, in a pilot in vitro investigation, 50 radiofrequency coagulations (3.2 W-22.4 W, pulse duration 10 s) were performed in ventricular preparations from freshly excised dog hearts. The correlation between applied radiofrequency energy and lesion volume was 0.87; the correlation between maximal catheter tip temperature and lesion volume was 0.82; the correlation between temperature integral and lesion volume was 0.9. In the intact dog heart, 44 radiofrequency pulses were delivered to the left and right ventricular endocardium in 12 anaesthetized dogs (exposure time: 10 s). Delivered power ranged between 5.6 W and 24.6 W; tissue impedance varied between 92 omega and 364 omega; lesion volume measured 0-273 mm3; developed peak temperatures ranged from 16.25 degrees C to 196 degrees C. The calculated integral beneath temperature curves measured 126-1971 degrees C.s. The correlation between applied radiofrequency energy and lesion volume was 0.32; the correlation between maximal catheter tip temperature and lesion volume was 0.61. Temperature integral correlated best with the assessed volume of myocardial necrosis (r = 0.7). No significant arrhythmogenic or haemodynamic side-effects were observed. Macroscopic examination showed a central depression surrounded by a zone of homogeneous coagulation. Vaporization and crater formation up to a depth of 4 mm were observed following three radiofrequency discharges. In two of these cases, rapid changes and oscillation of catheter tip temperature were observed. Thus, monitoring of catheter tip temperature during radiofrequency energy application improves the prediction of lesion size. In addition, temperature monitoring might improve the safety of the procedure with respect to the risk of perforation. PMID- 2591399 TI - Doppler echocardiography in the evaluation of tricuspid stenosis. AB - Seventeen patients (12 with native and five with prosthetic tricuspid valves) with tricuspid stenosis were studied by Doppler echocardiography followed by cardiac catheterization within 24 h. The mean tricuspid diastolic pressure gradient was calculated using the modified Bernoulli equation. Tricuspid valve area (TVA) was calculated by the pressure half-time method (TVA = 190 divided by pressure half-time). Data from Doppler echocardiography and cardiac catheterization were compared. The Doppler-derived tricuspid mean diastolic gradient was 1.9-9.9 mmHg (average 5.3 +/- 2.5 mmHg), which correlated moderately well with the catheterization-determined mean diastolic gradient of 2-17 mmHg (average 7.3 +/- 4.0 mmHg), R = 0.74, standard error of the estimate (SEE) 1.70 mmHg, Y = 0.45 x + 2.00, P less than 0.001. The Doppler-derived TVA was 0.56-1.58 cm2 (average 1.06 +/- 0.32 cm2), which correlated well with the catheterization determined TVA of 0.4-2.2 cm2 (average 1.06 +/- 0.46 cm2), R = 0.81, SEE = 0.20 cm2, Y = 0.56 x + 0.46, P less than 0.001. Of 12 patients undergoing right ventricular angiography, the angiographic and Doppler grades of tricuspid regurgitation matched exactly in six and differed by one grade in the remaining six. This study demonstrated that Doppler echocardiography compares very well to cardiac catheterization in the quantification of tricuspid stenosis and in the assessment of concomitant tricuspid regurgitation. PMID- 2591400 TI - HLA-haploidentical bone marrow transplantation in three infants with adenosine deaminase deficiency: stable immunological reconstitution and reversal of skeletal abnormalities. AB - Three infants with severe combined immunodeficiency and adenosine deaminase (ADA) deficiency were treated by T-cell depleted bone marrow transplantation (BMT), using human leukocyte antigen (HLA)-haploidentical parents as donors. In the first patient, two initial transplants failed to engraft and no change of the immunodeficiency was observed. In order to overcome this graft resistance, cytoreductive conditioning was used prior to a third transplant. In the other two patients, similar conditioning was used prior to initial transplants. In all three patients, complete and permanent immunological reconstitution was observed and they survive from 3.5 to 5 years after transplantation. In biopsies obtained from iliac bones prior to BMT, osteochondral abnormalities characteristic of ADA deficiency were noted in all three patients. After successful transplantation, these abnormalities had completely resolved. Our results demonstrate that cytoreductive conditioning prior to HLA-haploidentical BMT is useful in order to obtain stable engraftment and reversal of abnormalities associated with ADA deficiency. PMID- 2591401 TI - Prolonged and secondary fever in childhood bacterial meningitis. AB - In order to study the causes of prolonged and secondary fever in bacterial meningitis, a group of 102 infants and children with proven bacterial meningitis were studied. The causative agent was Haemophilus influenzae in 58% of patients, Streptococcus pneumoniae in 25% and Neisseria meningitidis in 17%. Prolonged fever was observed in 12% of the patients. The established causes include, in order of frequency, subdural effusion, drug fever, otitis media, gastroenteritis and urinary tract infection. Secondary fever was noted in 18% of the patients. The causes, in order of frequency, were urinary tract infection, subdural effusion, otitis media, phlebitis, pneumonia and drug fever. Neither relapse of the meningitis nor inadequate response to antibiotic therapy was the cause for prolonged or secondary fever. Neurological sequalae were observed in 21 patients. There was no correlation between prolonged or secondary fever and neurological sequalae. We conclude that prolonged and secondary fever in patients with treated bacterial meningitis is rarely caused by the primary infection. PMID- 2591402 TI - Familial combination of brachydactyly, type E and atrial septal defect, type II. AB - Nine members of a three generation family were affected with the combination of brachydactyly, type E and heart defect, mainly atrial septal defect, type II. A similar malformation pattern of autosomal dominant origin has not previously been delineated. PMID- 2591403 TI - Direct detection of a major mutation responsible for phenylketonuria in the population of the Federal Republic of Germany. AB - Forty-six individuals having phenylketonuria (PKU) alleles at the phenylalanine hydroxylase (PAH) locus were tested for the haplotype 2 PKU mutation by allele specific hybridization following in vitro DNA amplification. Patients and carriers previously shown to have a mutant haplotype 2 PAH allele demonstrated conservation of this mutation. In vitro DNA amplification greatly facilitated this analysis and provides the possibility of population screening for 37% of the mutant German PAH alleles. PMID- 2591404 TI - Renal vein thrombosis and response to therapy in a newborn due to protein C deficiency. AB - A newborn infant was diagnosed as having renal vein thrombosis due to heterozygous protein C deficiency and no other predisposing factor for thrombosis. He responded adequately to treatment with streptokinase, fresh frozen plasma and subsequent anticoagulation with heparin and warfarin (Coumadin). Four years from diagnosis he remains well with no recurrence of thrombosis and with normal renal function. PMID- 2591406 TI - Dosage of nifedipine in hypertensive crises of infants and children. AB - Eight hypertensive crises (HC) were treated with 2.5 mg of sublingual nifedipine in three children with weights below 10 kg (group A); 16 HC in 6 children between 10 and 20 kg with 5 mg (group B); and 40 HC in 10 children over 20 kg with 10 mg of nifedipine (group C). The relative decrease in both systolic and diastolic blood pressure was similar in all groups. The decrease was more rapid in groups A and B when the contents were extracted from the capsule and given directly. The hypotensive effect lasted 4 h. There were no side effects. The effective and safe single dose of nifedipine has been established to be 2.5 mg for children weighing less than 10 kg, and 5 mg for children weighing between 10 and 20 kg. PMID- 2591405 TI - The offspring of mothers with anorexia nervosa: a high-risk group for undernutrition and stunting? AB - Seven children from three families presented with stunting and low weight-for height. Their mothers had a history of anorexia nervosa (AN). Evidence was gathered that the children were nourished insufficiently, possibly in combination with psychosocial deprivation. Low growth hormone secretion was documented in three cases. With the increasing ability to induce fertility in anorectic women one should be aware of the effects of maternal AN on the offspring. PMID- 2591407 TI - Pharmacokinetics of intra-arterial indomethacin treatment for patent ductus arteriosus. AB - We present pharmacokinetic data of prolonged, intra-arterial indomethacin treatment (i.e. induction plus maintenance dose) for symptomatic patent ductus arteriosus (sPDA) in 26 ventilated premature infants. sPDA was assessed by two dimensional and pulsed Doppler echocardiography. Permanent ductal closure occurred in 20 (76%) infants. Plasma levels of indomethacin were 1.18 +/- 0.74; 1.8 +/- 1.0; 1.51 +/- 0.93 and 1.25 +/- 0.98 micrograms/ml (mean +/- SD) at 12, 24, 48 and 72 h after initial dose administration. All except one patient who responded with ductal closure, showed plasma levels above 0.25 microgram/ml throughout the 3 day treatment period and no case of sPDA reopening was noted. Although target concentrations over time were not defined, the data indicate that the maintenance levels measured were within the therapeutic range. A negative correlation was found for plasma drug levels and postnatal age (r = 0.52; P less than 0.01). Volume of drug distribution was 0.23 +/- 0.18 l/kg, total clearance 0.1 +/- 0.11 ml/min and elimination constant 0.06 +/- 0.05 h-1 (mean +/- SD). The great variation in pharmacokinetic data reflects the heterogeneity of the population studied with respect to extracellular fluid space, cardiovascular status, serum protein and other parameters. PMID- 2591408 TI - Intestinal milk-bolus obstruction in premature infants. PMID- 2591409 TI - Diameter of coronary arteries in infancy. PMID- 2591411 TI - Autoimmune thyroiditis presenting as painful thyroiditis. PMID- 2591410 TI - Hypercalciuria and nephrolithiasis in Wilson disease. PMID- 2591412 TI - Simple method of umbilical artery catheterization. PMID- 2591413 TI - Seasonal variations of glycosylated haemoglobin in diabetic children. PMID- 2591414 TI - Autoimmune involvement in Cushing syndrome due to primary adrenocortical nodular dysplasia. AB - Cushing syndrome due to primary adrenocortical nodular dysplasia was diagnosed in two patients, aged 3 years 9 months and 9.5 years. Subsequently, adrenalectomy was performed and followed by steroid replacement. In both cases, the adrenals were normal or only slightly enlarged and showed adrenocortical nodular dysplasia histologically. Small lymphocytic infiltrates consisting of T-cells and class II MHC positive macrophages were present in adrenal specimens of both the patients. Samples of protein A sepharose purified serum immunoglobulins from both children stimulated adrenocortical DNA synthesis and cortisol production in cultured guinea-pig adrenal segments in vitro in a dose dependent fashion. Adrenal stimulating immunoglobulins were also demonstrated in serum specimens of both patients' mothers. However, none of them had overt signs of adrenal disease. Our data support the view that autoimmune mechanisms may be involved in primary adrenocortical nodular dysplasia. PMID- 2591415 TI - Studies on zinc sulphate microcapsules: (III) in vivo evaluation. AB - Zinc sulphate capsules and syrup were prepared as conventional dosage forms and in vivo experiments were performed for both on the conventional dosage forms as well as on microcapsules. Blood samples were taken from healthy volunteers at 1, 2, 3, 4 and 5 hours and AUC3 and AUC5 were calculated by trapezoidal rule. Relative bioavailability of zinc was calculated and the 5th hour relative bioavailability difference was found to be significant. The results show that zinc sulphate in microcapsule form was able to prolong the action. PMID- 2591416 TI - The pharmacokinetics and tissue distribution of gomphoside in Wistar rats. AB - The excretion and tissue distribution of [3H]-gomphoside was studied after i.p. and i.v. administration of the cardiac glycoside (1 micrograms/g) to male Wistar rats. Following an intraperitoneal dosage of [3H]-gomphoside, most of the radioactivity (greater than 80%) had been excreted from the body by the end of 48 hours. Biliary excretion played a major role in elimination of [3H]-gomphoside with 90 +/- 15% of radioactivity being collected in 24 hours. Renal excretion formed a minor route of elimination of the cardiac glycoside; only 6 +/- 2% being excreted over 6 days. The distribution of radioactivity to tissues after an intravenous dose was rapid; most of the dose was located in the liver (32%), and the skeletal muscle (31%) 3 minutes after injection. The pharmacokinetics of [3H] gomphoside could be described by a two-compartment open model with an average elimination half-life of 3.7 hours, and a large volume of distribution (2.3 +/- 0.3 ml/g body weight) characteristic of the commonly used cardiac glycosides (1). PMID- 2591417 TI - Metabolism of nafronyl in man. AB - The metabolism of nafronyl (I) has been studied in man. In addition to small amounts of the parent compound, three acidic metabolites were extracted from urine. The chemical structures of all metabolites were determined by using mass spectrometry and [1H]-NMR spectroscopy as tetrahydro-beta-(1-nephthalenylmethyl) 2-furanpropionic acid (II) and two stereoisomers of 3-(1-naphthalenylmethyl) tetrahydrofuran-2-one-5-propionic acid (III, IV). The biodegradation products III and IV are formed after oxidation of the tetrahydrofuran system in II, hydrolytic ring opening of the gamma-butyrolacton and a subsequent formation of a gamma butyrolacton ring with the second carboxyl group. The three metabolites represent the major fraction of unconjugated products in the urine of man after administration of nafronyl. PMID- 2591418 TI - Chronopharmacokinetic and bioequivalence studies of two formulations of trimipramine after oral administration in man. AB - The bioavailability of two oral formulations of trimipramine, tablets and solution, was performed in twelve healthy volunteers, in a cross-over study. Each formulation was administered in the morning after a fasted period, and in the evening after a meal, in order to evaluate the role of both administration time and food consumption on the plasma kinetic parameters, under usual therapeutic conditions. A high interindividual variability of data was found. First, the extent of bioavailability was identical for the two formulations but the rate of bioavailability seemed to be different, with the p.o. solution, being more rapidly absorbed (tmax = 1.50 h). The effect of administration time was more obvious for the solution as shown by a lower quantitative absorption as well as a delay in time to reach the maximal concentration. Regardless of formulation and administration time, the t1/2 beta was about 10 hours and the mean MRT value was 11 hours. PMID- 2591419 TI - Pharmacokinetic and pharmacodynamic modelling of metoprolol in rabbits with liver failure. AB - The pharmacokinetic and pharmacodynamic profiles of metoprolol were studied in adult male rabbits given 3.2 mg/kg i.v. before and during liver failure. The partition of metoprolol between blood cells and plasma averaged 1.14 in both conditions. Plasma protein binding, concentration-independent, was 32% and 17% in normal and pathological status, respectively. With normal liver function the terminal elimination half-life for the drug was 0.54-0.96 h, rising to 1.0-2.1 h in liver failure. Differences of the same order were observed for total plasma drug clearance (average 3.7 vs 1.5 1/h/kg), MRT (0.77 vs 1.92 h), AUC (0.9 vs 2.2 mg h/l) and k10 (3.17 vs 1.80 h-1). Liver impairment did not affect the volume of distribution of the central compartment, the steady-state volume of distribution and the other intercompartmental rate constants. Although metoprolol was eliminated in the urine, the amount excreted was low (1.5% of the administered dose) in both conditions. The pharmacokinetic model was extended by an 'effect compartment', which has no influence on the predetermined mass of drug in the body, to analyse the relationship between heart rate fall and changes in metoprolol plasma concentrations. After drug administration, heart rate fell rapidly about 90 beats in both states. The mean unbound plasma concentration producing 50% of this reduction was double during liver failure compared to normal condition (0.03 vs 0.07 mg/l), but the temporal aspects of drug equilibration with site of action were similar. PMID- 2591420 TI - Pharmacokinetics, tissue distribution and placental permeability of tetrahydro tetramethyl-naphthalenyl-propenyl benzoic acid (a retinoidal benzoic acid derivative) in hamsters. AB - Tritiated tetrahydro-tetramethyl-naphthalenyl-propenyl benzoic acid (TTNPB; Ro 13 7410) was administered as a single oral bolus to pregnant hamsters (day 8) to determine the maternal plasma pharmacokinetic profile and peripheral tissue distribution patterns. Blood and tissue, including embryo or fetus, were collected at specific time intervals to 96 h and assayed for total radioactive compounds and/or parent retinoid. No lag time was required to describe retinoid absorption (t 1/2 pi = 1.2 h) with peak plasma levels at 2.4 h; the concentrations then declined with exponential elimination from the central compartment (t 1/2 e = 3 h). The maximum concentrations of circulating radioactive compound or metabolites after 100 micrograms/kg [3H]2-TTNPB occurred in liver greater than fetus greater than adrenal greater than lung approximately equal to kidney greater than plasma; after 1000 micrograms/kg, maternal liver accumulated the highest concentration followed by plasma greater than fetus = placenta = uterus. An unidentified, polar metabolite was detected in plasma at 0.5 h and by 12 h constituted greater than 90% of the total circulating radioactivity. TTNPB was absorbed and cleared more slowly, concentrated in the conceptus to a higher degree and possessed greater intrinsic activity than the naturally-occurring tetraene retinoids. These properties contribute to the marked teratogenic activity of TTNPB as compared to the tetraene retinoids. PMID- 2591421 TI - Pharmacokinetics and antiarrhythmic efficacy of intravenous ajmaline in ventricular arrhythmia of acute onset. AB - 21 patients with acute myocardial infarction and ventricular arrhythmia of Lown class II-IIIB of acute onset received a short infusion of (50 mg/5 min) ajmaline (Gilurytmal). 6 of the patients had normal kidney and liver function (Group 1), 4 patients had acute renal failure and hemodialysis treatment (Group 2), 4 patients had impaired hepatic function (Group 3), 3 patients had cardiogenic shock (Group 4), and 4 patients had been pretreated with phenobarbital for seizures for at least 5 days (Group 5). A distribution half-life of 6 +/- 1 min and an elimination half-life of 95 +/- 6 min was determined in Group 1. The total plasma clearance was significantly lower in patients with impaired liver or cardiac function and significantly higher in Group 5, whereas impaired renal function did not affect total plasma clearance. After short infusion, ventricular arrhythmia of Lown II-IIIB completely disappeared for at least 16 to 36 min (mean: 19 min), which was associated with an ajmaline plasma level of 0.1-0.45 micrograms/ml. Additionally, steady-state plasma levels of ajmaline were determined after continuous infusion of 10-50 mg/h to 16 patients (Group 6) with ventricular arrhythmia of acute onset (Lown class IVA-V). Ventricular arrhythmia completely disappeared or at least changed to lower Lown classes at ajmaline plasma levels of 0.4-2.0 micrograms/ml. The ajmaline plasma protein binding was 76 +/- 9%. Ajmaline had a special affinity to alpha 1-acid glycoprotein. PMID- 2591422 TI - Pharmacokinetic and nephrotoxic study of gentamicin in rabbits using a new dosage regimen. AB - Currently, in certain clinical situations there is an increasing trend towards using dosage regimens involving aminoglycoside antibiotics based on the administration of a single dose of the drug per day instead of administering the same amount in two or three administrations. The aim of the present study was to discover the pharmacokinetic profile and the nephrotoxic potential of this new form of administration in experimental animals receiving gentamicin. The study was conducted on two groups of rabbits, one of which received a single dose of the drug at 7 mg/kg i.v. and the other 7 mg/kg administered every 12 hours, allometrically equivalent to gentamicin dosing at 5 mg/kg every 24 hours to human subjects. The number of doses administered was 20. From the pharmacokinetic point of view, the results point to the existence of a significant degree of accumulation of the antibiotic in renal cortex as a result of the dosage regimen, no important modifications occurring in the pharmacokinetic parameters of gentamicin calculated from its plasma kinetics. This shows that the two compartment model employed predicts drug levels in accessible tissues but not in deep ones where gentamicin is accumulated for long periods of time. From the toxicological point of view, the treatment caused appreciable damage of the renal tubules during the first phases of the treatment which was not detectable from the serum creatinine levels or the kinetic behaviour of the aminoglycoside. PMID- 2591423 TI - Bladder tumors invading the lamina propria (stage A/T1): influence of endovesical bacillus Calmette-Guerin therapy on recurrence and progression. AB - 47 patients with transitional cell bladder carcinoma invading the lamina propria (stage A/T1) were treated from 1984 to 1986 by complete transurethral resection followed by 1-3 cycles of endovesical bacillus Calmette-Guerin instillations, and followed 14-64 months by cytology, endoscopy and bladder biopsies, 64% achieved a complete response, 36% recurred (recurrence rate/100 months/patient 2.2), 21% progressed to muscle invasion. Duration of treatment, tumor size or type (solid vs. papillary), presence of carcinoma in situ bore no relation to the final result. The preceding history of T1 bladder tumor appeared associated with a higher risk of progression although not reaching statistical significance. The results were compared to those obtained by transurethral resection in a similar group of 50 patients treated from 1982 to 1984 and followed up 12-100 months, 90% recurred and 34% progressed to muscle invasion with a recurrence rate/100 months/patient of 9.22. Keeping in mind the limits of a nonrandomized historical comparison, it appears that endovesical bacillus Calmette-Guerin therapy alters favorably the recurrence pattern of T1 bladder cancer. PMID- 2591424 TI - ESWL management of ureteral calculi without anesthesia: an alternative to invasive procedures. AB - We reviewed our experience with ESWL therapy in 96 patients who presented with upper, middle and lower ureteral calculi; we had 127 treatments in 96 patients, 73 men (76%) and 22 women (24%). All the treatments were performed without general anesthesia and without premedication. The average number of shock waves was 3.000. Repetition of the ESWL therapy had to be performed in 25%. PMID- 2591425 TI - Management of regional lymph nodes in carcinoma of the penis. AB - In the management of carcinoma of the penis, standard treatment of the primary tumor is by radiotherapy for small lesions (Tis, T1, T2 located in the glans) and by amputation in other cases (T2 with invasion of the shaft). The diagnosis and treatment of regional lymph nodes are thus the essential problems with this cancer. In our series of 45 patients with a minimum 5-year follow-up, clinical assessment was incorrect in 22.5% of cases (22% of the patients with negative bilateral biopsy of the superficial inguinal nodes developed metastases), and many of the complications (flap necrosis, lymphedema) occurring after inguinal lymphadenectomy contributed to a poorer quality of patient survival. A therapeutic approach to the management of regional lymph nodes in order to combat the carcinoma more effectively and improve patient survival quality is suggested. PMID- 2591426 TI - Prognostic parameters in renal cell carcinoma--a new approach. AB - The prognostic potential of the parameters TNM staging, Robson staging, grading, cell type, growth pattern, and patient age was investigated for 431 patients with operated renal cell carcinoma (RCC). In the individual analyses, staging and grading attained the best results, whereby Robson staging proved to be superior to TNM staging by comparison. Morphological parameters had a more modest effect on the prognosis, but this should not be underestimated. A scale of points based on a comparative biometric evaluation of the various parameters was devised. From this scale, three significantly distinct prognostic groups evolved with a correct prognosis of over 80% on the average for an individual case. In comparison with other proposals for assessing prognosis for RCCs, the suggested scale of points had the greatest prognostic potential. PMID- 2591427 TI - Some observations on the regeneration of smooth muscle in the repaired urinary bladder of the rabbit. AB - The regeneration of smooth muscle appears to take place within the fibrous tissue characteristically found when a biodegradable collagen/Vicryl prosthesis is used to repair full thickness defects in the rabbit urinary bladder. The question of whether the central smooth muscle was the result of myoblastic differentiation in the fibrous tissue or arose from healthy pre-existing detrusor muscle was resolved by serial sectioning and specific staining. Only in situ transmutation, or differentiation, explains the morphology, and the results therefore strongly suggest that this central smooth muscle regenerated from within the repair area. PMID- 2591428 TI - Role of natural killer cells in bladder tumor. AB - The role of natural killer (NK) cells in bladder tumors was assessed from the aspect of local and systemic immune responses. The NK cell activity was measured in a 4-hour 51Cr-release assay. The NK activity in patients with bladder tumor was lower, though not significantly, than that in normal individuals. In patients with bladder tumor, the NK activity was significantly lower in invasive tumors and lymph node metastases. Moreover, the NK activity was lower in those who died (n = 4) than it was in survivors (n = 21). In an in vitro experiment, OK432 significantly augmented the NK activity in peripheral blood lymphocytes (PBL), however, this augmentation was not always OK432 dose-dependent. The augmented NK activity induced by OK432 occurred even in patients with invasive tumors. On the other hand, the spontaneous NK activity in tissue-infiltrating lymphocytes (TIL) and lymph node lymphocytes (LNL) was significantly lower than that in PBL. In these three groups, the NK activity was significantly increased by OK432, this rate of increase was highest in TIL, followed by LNL and PBL. Further studies are required to elucidate the role of NK cells in bladder tumor, from the aspect of local and systemic immune responses. PMID- 2591429 TI - Secondary megaureters in children: results of treatment. AB - Treatment results of 74 secondary megaureters in 48 children (25 males and 23 females with one segmental and 73 total megaureters) are presented. The left side prevailed over the right one (ratio 1.4:1.0); the lesion was bilateral in 54%. Forty-two children (88%) were treated surgically. Eleven megaureters (15%) were modelled. and 2 megaureters had to be reoperated. The follow-up period ranged between 7 months and 9.5 years. Urinary infection was reduced from 80 to 54%, chronical renal failure was reduced from 65 to 54%, and the occurrence of arterial hypertension remained unchanged. Excellent results were achieved in 27%, they were satisfactory in 60% and poor in 13% of the megaureters. PMID- 2591430 TI - Surgical correction of severe Peyronie's disease without plaque excision. A new approach. AB - We report 5 cases of severe Peyronie's disease treated by a new procedure. It consists of making parallel I-shaped incisions on the dorsal face of the penis so that the shortened part of the albuginea can increase. The 2 defects are covered with 2 patches of dura mater. All the cases except one had good results, either plastic or sexual. We think this type of surgery is indicated to correct severe angulation and shortening of the penis in men with normal sexual lives. PMID- 2591431 TI - Ureterosciatic hernia. A rare cause of pyonephrosis. AB - A female patient presented as an emergency case with pyonephrosis and septicemia as a result of ureterosciatic hernia. Septicemia was treated successfully by immediate percutaneous nephrostomy tubing. After complete disappearance of symptoms, the hernia was closed operatively. Topographic anatomy of ureterosciatic hernia is presented. PMID- 2591432 TI - Squamous cell carcinoma of the renal pelvis presenting with a loin sinus. AB - An unusual presentation of a renal pelvis squamous cell carcinoma is reported; a loin sinus with excessive pyorrhea was the only complaint of a man with a long history of renal calculus disease. PMID- 2591433 TI - A phase I clinical and pharmacokinetic study of Brequinar sodium, DUP 785 (NSC 368390), using a weekly and a biweekly schedule. AB - Brequinar, DUP 785, is a substituted 4-quinoline carboxylic acid derivative which in preclinical studies has shown broad antitumor activity. It is a novel antimetabolite blocking pyrimidine nucleotide synthesis. In a clinical phase I study, 83 patients were treated on a weekly schedule and 18 patients on a biweekly schedule. The drug was given intravenously as a short infusion. Three patients were entered on each dose level from a starting dose of 6 mg/m2 up to 2600 mg/m2 weekly. The dose ranges on a biweekly schedule were 500-850 mg/m2. There was no dose escalation in individual patients. Pharmacokinetic studies were performed in 19 patients on a weekly schedule and in two patients on a biweekly schedule. A biphasic decay in plasma was observed with a median half life of 10 h (5.1-23.4). The main dose-limiting toxicity was thrombocytopenia. Of non hematologic side-effects, stomatitis/mucositis occurred frequently. Skin eruptions occurred rarely, but were a major problem when found. All side-effects were fully reversible; there were no signs of cumulative toxicity. Antitumor activity was observed in one patient with a lung metastasis from a bladder cancer and in a patient with an unknown primary tumor. The recommended doses for phase II trials with DUP 785 are: 1500-2000 mg/m2 on a weekly schedule and 500-750 mg/m2 on a biweekly schedule dependent on status before treatment. PMID- 2591434 TI - Vascular collapse after flavone acetic acid: a possible mechanism of its anti tumour action. AB - Flavone acetic acid (FAA, LM 975) causes regression and growth retardation in several solid murine tumours. The mechanism of action is unknown, although various lines of evidence suggest an indirect cytotoxic effect. We have carried out preliminary studies on the effect of FAA on relative blood flow in six experimental murine tumours using 86RbCl extraction. We have also measured growth delay after treatment with the same dose of FAA (200 mg/kg). The data show that the drug induces a drop in tumour perfusion within 6 h of treatment in all of the tumours, and that this can be correlated with the growth delay measured. We conclude that vascular collapse may be an important component of the action of this drug, and that further investigation of this phenomenon is warranted. PMID- 2591435 TI - A morphometric study of the vascularity of oral squamous cell carcinomas and its relation to outcome of radiation therapy. AB - In 26 patients the vascular morphology of pretreatment biopsies from oral squamous cell carcinomas (scc) was studied. Patients had been treated by radiation alone and followed up for 25-73 months. Vascular endothelial cells were identified using antifactor VIII staining. The distances from 700 randomly selected tumor cells to the closet blood vessel were measured in each tumor. Stepwise logistic regression analysis revealed that tumors with fewer than 21% of the morphologically intact tumour cells located within 48 microns of the closest blood vessel had a better control rate than tumors with a higher proportion of tumor cells within this distance. Using the analysis as a predictive assay, local tumor control was predicted from a single histological section with a sensitivity of 81% and a specificity of 60%. In correctly predicted cases of local control, the average median distance between tumor cells and blood vessels was 105 microns. These tumors formed well differentiated avascular tumor cell nests that were surrounded by stroma and blood vessels. Mitotic figures were observed only in the outer rim of cell nests while the center was often keratinizing or necrotic. In cases of correctly predicted treatment failures the average median distance from intact tumour cells to capillaries was 76 microns. These tumors showed varying degrees of organization and capillaries penetrating tumor cell areas. Clinical outcome of radiation therapy of oral scc appears to be correlated with different patterns of tumor architecture and blood supply. PMID- 2591436 TI - Population attributable risk for endometrial cancer in northern Italy. AB - The population attributable risk for endometrial cancer has been estimated in relation to its four major risk factors (overweight, estrogen replacement therapy, diabetes and hypertension) using data on 528 cases and 1626 controls collected within the framework of a hospital-based case-control study conducted since 1981 in the greater Milan area, northern Italy. Over 30% of the endometrial cancer cases diagnosed in the study population could be attributed to overweight, 10% to postmenopausal estrogen replacement therapy, and similar proportions (around 10%) to hypertension and diabetes. The overall estimate including the joint effect of the two conceptually preventable factors (overweight and estrogen use) was 40%, while further inclusion of diabetes and hypertension, which are not easily preventable per se but are still closely linked to 'westernization', indicated that over 50% of cases were attributable to the combined effect of these four factors. The validity of these findings, in strict terms, is limited to this area from northern Italy. However, they can be taken as a general indication of the scope for prevention of endometrial cancer in other southern European populations, sharing similarities in lifestyle and pattern of hormonal replacement therapy use. PMID- 2591437 TI - A dose finding study of prochlorperazine as an antiemetic for cancer chemotherapy. AB - This phase I study determined the maximum tolerated dose of prochlorperazine when used as an antiemetic prior to cytotoxic chemotherapy. Initially, cohorts of three patients were given prochlorperazine at escalating doses of 0.2, 0.4, 0.6, 0.8, 1.0 and 1.2 mg/kg as an intravenous infusion over 20 min. The maximum tolerated dose was 1.2 mg/kg. The dose-limiting toxicity was hypotension which was reversed by a fluid load. The other major toxicities were extrapyramidal reactions which were dose related. All patients at the 1.2 mg/kg dose reported restlessness while five of six were restless and two of six at 1.0 mg/kg had muscle spasms. Two of seven patients reported restlessness at the 0.8 mg/kg level. Sedation and dry mouth were reported at all dose levels but were more common at higher doses. Prochlorperazine in plasma was assayed by high performance liquid chromatography with electrochemical detection and pharmacokinetics were determined for three patients at the 1.0 mg/kg dose level. The average terminal elimination half life was 7.6 +/- 0.4 h, plasma clearance 27 +/- 5 ml/min/kg and volume of distribution 17.7 +/- 4.5 l/kg. The dose of prochlorperazine recommended for further studies of antiemetic efficacy is 0.8 mg/kg intravenously. PMID- 2591438 TI - Quantitative transplantation assays of the rat rhabdomyosarcoma BA1112 isografts into the WAG/Rij Y rat and xenotransplantation into the athymic NCr (nu/nu) nude mouse. AB - Quantitative tumor cell transplantation assays have been performed to compare the transplantability of rat rhabdomyosarcoma BA1112 into isologous WAG/Rij Y rats and athymic NCr(nu/nu) nude mice. The end-point was the TD50 or the number of viable tumor cells which would transplant the tumors into half of the recipients. At Yale, two sets of 2-fold dilutions were prepared, one was sent to the MGH by Air Express. That afternoon, concurrent assays were performed at Yale using the WAG/Rij Y rat and at MGH using the NCr(nu/nu) mouse. The TD50 values were the same for iso- and xenotransplantation. Furthermore, the TD50s in rats and mice were unaffected by standard immunization procedures prior to challenge of the TD50 assay. The BA1112 (10(7) trypan blue excluding cells) grew to 10-12 mm and then completely regressed if transplanted into NCr(nu/+) mice which had received 6 Gy whole body irradiation but did not grow in control NCr(nu/+) mice. The times for the BA1112 to grow to 10 mm were the same in normal or preimmunized WAG/Rij Y rats or NCr(nu/nu) mice and in 6 Gy WBI NCr(nu/nu) mice. All of the experimental data show that the xenogenic NCr(nu/nu) mice accept the BA1112 as readily as do the isologous WAG/Rij Y rats. PMID- 2591439 TI - Making cancer statistics more informative: measures of the quality of recorded diagnosis in a population-based registry. AB - The quality of the recorded diagnosis is a major limit to the usefulness of Cancer Registry statistics that is easily overlooked by users of the data. With data from a large population-based cancer registry as an example, we demonstrate how Registry statistics could be improved by wider use of three simple indices, namely (1) the proportion histologically verified (adjusted for age), (2) the proportion of verified cases with an uninformative diagnosis, and (3) the proportion of cases that are staged. We believe that greater awareness of the deficiencies of Cancer Registry statistics will lead to a more critical interpretation of them, and help stimulate efforts to rectify matters. PMID- 2591440 TI - Selective internal radiation therapy: distribution of radiation in the liver. AB - Selective internal radiation therapy for primary and secondary liver cancer involves the intra-hepatic arterial injection of microspheres containing yttrium 90. The microspheres become entrapped primarily in, and thus preferentially irradiate, tumour tissue. During a clinical trial with this therapy it has been possible to take tumour and normal liver tissue samples, after microsphere injection, and measure their specific activity. Absorbed tissue radiation doses were then calculated for tumour and normal tissue samples from a total of nine patients. The mean tumour to normal tissue ratio for radiation dose for the nine patients was approximately 6:1 with a range of 0.4:1-45:1. Injection of similar amounts of activity in different patients resulted in markedly differing tissue doses depending on liver size and tumour burden. Normal liver tissue doses of between 9 and 75 Gy were measured while corresponding tumour tissue doses ranged from 34 to 147 Gy. Selective internal radiation therapy, combined with the blood flow changes resulting from angiotensin II administration, can provide preferentially high radiation doses to tumour tissue within the liver whilst relatively sparing the surrounding normal liver tissue. PMID- 2591441 TI - In vivo and in vitro effects of the antifungal agent miconazole on estrogen biosynthesis in human breast cancer. AB - This study was undertaken to investigate whether miconazole (MCZ), an antifungal agent, inhibits aromatase activity in human breast cancer tissue preparations (n = 6). Aromatase activity in breast cancer tissue was significantly suppressed by an addition of MCZ (1 microM). The aromatase inhibition rate of MCZ was in the range 15-58%. The change of androgen and estrogen levels was also examined in peripheral blood after administering MCZ (200 mg) intravenously to four patients both with breast cancer and two with systemic fungal infection. Serum androstenedione and testosterone levels fluctuated only little. However, serum estrone and estradiol levels tended to decrease after administration of MCZ. These results suggest that MCZ may be useful in the treatment of breast cancer. PMID- 2591442 TI - Influence of the synthetic microtubule inhibitor erbulozole (P.I.N.N.) (R 55 104), a new tubulozole congener, and gamma irradiation on murine tumors in vivo. AB - Erbulozole (P.I.N.N.) (R 55 104) is a more water soluble congener of the synthetic microtubule inhibitor tubulozole (R 46 846) exhibiting a reversible antimicrotubular activity in vitro at a dose (1.56 x 10(-8) M) which is at least 10-fold lower. The compound also has an antiinvasive potential and shows antitumoral effects both in vitro and in vivo when administered appropriately. Eighty mg/kg R 55 104, given orally 6 h before or 3 h after radiotherapy, displays a prominent interactive effect with 10 Gy gamma irradiation in subcutaneous murine tumors which is similar to 160 mg/kg tubulozole administered 6 h before 10 Gy. The enhancing effect is also observed in a clinically relevant radiation dose fractionation schedule whereby eight fractions of 2 Gy each were pretreated 2 h before with 40 mg/kg R 55 104. Further study of this radiochemotherapeutic combination may lead to new clinical applications. PMID- 2591443 TI - A phase II study of a 21 day continuous infusion schedule with epirubicin in advanced gastric cancer. PMID- 2591444 TI - Hyporesponsiveness of macrophages from C3H/HeJ (endotoxin-resistant) mice to the antitumour agent flavone acetic acid (NSC 347512). PMID- 2591445 TI - Bone marrow transplantation versus chemotherapy in acute non-lymphocytic leukemia: a meta-analytic review. PMID- 2591446 TI - Daunorubicin-induced mammary tumors in the rat. AB - Eleven of 24 female Sprague-Dawley rats given a single i.v. injection of daunorubicin (10 mg/kg) developed mammary tumors within 8 months after the injection. Four of 12 rats given an intramammary injection of daunorubicin (4 or 8 micrograms) developed five mammary tumors in the injected area within 6.5 months of injection. Tissue distribution studies using tritiated daunorubicin revealed that the liver, kidney, lung, heart, and intestine had higher daunorubicin concentrations than mammary tissue during the first 24 h after i.v. injection. However, depletion of the drug from the internal organs was more rapid than from mammary tissue. Differences in ability to metabolize daunorubicin were compared in homogenates of isolated mammary epithelial cells and hepatocytes by high-performance liquid chromatography: after 90 min, hepatocytes metabolized about 70% of daunorubicin, whereas mammary epithelial cells did not metabolize the drug. Tritiated daunorubicin injected directly into rat mammary gland showed no metabolism in 24 h, and the drug did not get into the circulation. These results suggest that retention of daunorubicin because of the inability of mammary tissue to metabolize the drug is a cause of drug-induced mammary tumors in female Sprague-Dawley rats. PMID- 2591447 TI - Experiences with SCC antigen, a new tumor marker for cervical carcinoma. AB - Squamous cell carcinoma (SCC) antigen was first described by Kato et al. in patients with carcinoma of the cervix uteri. SCC serum levels can be measured with a radioimmunoassay. In our investigation, 2.0 ng/ml was taken as the upper limit of the standard range. In 35 healthy women there were no elevated SCC serum levels. Eight of 40 patients with breast, endometrial and ovarian cancer had raised SCC levels. In only two of 12 patients with benign gynecological diseases, SCC was also elevated. Sixty per cent of the patients with primary and 73% of the patients with recurrent cervical cancer showed pathological values; CEA was elevated in 31% and 51% respectively. The absolute values increased with the stage of the disease. Sixty-nine per cent of patients with squamous cell carcinoma had elevated levels. In five of nine adenosquamous carcinomas SCC was pathological. SCC shows a high sensitivity for squamous cell carcinomas of the cervix uteri. The tumor marker might be helpful in the control of primary therapy and follow-up of cervical cancer patients. PMID- 2591448 TI - Low dose cytosine-arabinoside has only minimal differentiation inducing capacity in HL60 cells. AB - Cytosine-arabinoside (ARA-C) in low doses induces complete remissions in myelodysplastic syndromes and acute leukemia. Evidence is accumulating that these remissions are not reached by differentiation induction but through cytotoxicity. In HL60 cells differentiation was measured by a comprehensive panel of quantitative and qualitative markers of maturation. After exposure to ARA-C (10( 7) M) for 4 days HL60 cells did not mature morphologically. Cell volume increased. The increase in esterase activity was small and did not reach the amount measured in normal monocytes. There was no significant difference in latex phagocytosis and NBT reduction between cultures with and without ARA-C. HL60 cells were arrested in S-phase and clonogenic capacity persisted. The observed changes after exposure to ARA-C seem to be caused by impeded cell division while synthesis of protein continues. We conclude that ARA-C in low dose exerts its effect by halting proliferation through cytotoxic effects and not by differentiation induction. PMID- 2591449 TI - A phase I study of immunostimulation and toxicity in patients with colorectal carcinoma using the immunomodulator 3,6-bis(2-piperidinoethoxy) acridine trihydrochloride (CL 246738). AB - Seventeen patients with residual or recurrent colorectal carcinoma were given a new synthetic immunomodulator [3,6-bis(2-piperidinoethoxy) acridine trihydrochloride CL246738) as part of a phase I clinical trial. No patients had undergone previous immunotherapy or chemotherapy. Detailed immunological studies including interferon levels, interleukin 2 levels, natural killer cell function, mitogen responses of lymphocytes, immunoglobulin levels and lymphocyte subpopulation levels were analysed in the patients who received this drug in an attempt to find out whether there was any biological activity identifiable in humans. None of the subjects showed any significant increases in post treatment values of the immunological parameters studied. Toxic effects of the drug at high doses included nausea, diarrhoea and decreased levels of consciousness. In conclusion, no immunological effects were identified following the administration of CL 246738 in human subjects with recurrent or residual colorectal cancer. PMID- 2591450 TI - Effects of stress on tumor growth and metastasis in mice bearing Lewis lung carcinoma. AB - The progression of Lewis lung carcinoma has been examined in mice under the stress of different housing and experimental conditions. The maintenance of the animals in a low stress environment decreased the weight of spontaneous lung metastases in comparison with conventional housing. The handling of mice in the low stress environment for intraperitoneal saline administration increased metastasis formation, whereas the application of a psychological stressor (spatial disorientation) to these animals increased both primary tumor growth and metastasis formation. These results indicate that psychological and experimental stressors can modulate, presumably via neuroendocrine mechanisms, the host's antitumor responses which can control metastases and primary tumor independently from each other. PMID- 2591451 TI - Ploidy level, histopathological differentiation and response to chemotherapy in serious ovarian cancer. AB - The ploidy level was measured in tumour specimens from 64 patients with advanced epithelial ovarian cancer (FIGO stages III and IV) by flow cytometric analysis. The same tumours were histopathologically graded based on a score system considering eight histopathological parameters. The results showed that both the histopathological grading index (HGI) and the DNA index were important to the frequency of complete pathological remission as assessed by second look operation. A combination of the two parameters allowed a division of the patients into three groups with different frequencies of complete pathological remission and survival. It is concluded that flow cytometric analysis and extended histopathological grading may be important adjuncts in the evaluation of malignant epithelial ovarian tumours. PMID- 2591452 TI - Serum interleukin 2 (IL-2) levels and prolactin bioactive/radioimmunoassay ratios of women at risk for breast cancer. AB - In a cohort of women at high risk for developing breast cancer we have observed that 74% of the women with prolactin BA/RIA ratios over 1.4 had detectable levels of IL-2 in their serum (990 +/- 400 mU/ml) and the IL-2 levels were correlated with the prolactin BA/RIA ratio (R = 0.79; P greater than 0.004). Women with BA/RIA ratios were either approximately 1.0 or less than 0.55 had lower levels of serum IL-2 (177 +/- 70 and 130 +/- 40 mU/ml, respectively). Detectable levels of serum IL-2 were found in 58% of those women with BA/RIA ratios of 1.0 and 55% of those with BA/RIA ratios less than 0.55. PMID- 2591453 TI - Clinical value of N-myc oncogene amplification in 52 patients with neuroblastoma included in recent therapeutic protocols. AB - Southern blot analysis of neuroblastoma (NB) cell DNA from 52 patients (58 samples) allowed the detection of an N-myc amplification on three of the 13 BM samples and three of 13 tumor samples at diagnosis, on two of 17 tumor samples taken after induction therapy, on three of seven BM samples and two of the five local tumor samples taken after relapse. N-myc was amplified in two of the 15 patients with stage I to III NB and in 10 of the 36 patients with stage IV neuroblastoma over 1 year of age. Conclusions from the analysis are as follows: first tumor samples obtained on previously treated patients are histologically modified and detection of N-myc amplification is not accurate; consequently N-myc amplification must be defined at diagnosis. Surgical biopsies of the primary tumors can, however, be delayed and malignant cells obtained by ultrasound-guided punctures or analyzed on bone marrow samples if they represent more than 50% of the total population. Second, any attempt to define the prognostic value must be performed on a group of patients treated with a new aggressive protocol of chemotherapy; it will require a multiparametric analysis including, in particular, results of an extensive clinical staging at diagnosis and histological criteria. PMID- 2591454 TI - Breast cancer and combined oral contraceptives: an Italian case-control study. AB - The risk of breast cancer in relation to use of oral contraceptives was evaluated using data from a hospital-based case-control study from Northern Italy on 1517 cases below age 60 and 1351 controls admitted for acute diseases unrelated to any of the known or potential risk factors for breast cancer. The multivariate relative risk for ever vs. never users was 1.3 (95% confidence interval = 1.0 1.7). However, the risk was not related to duration of use: indeed the highest risk was observed among short-term users (less than 2 years), and the point estimate was 0.9 among users for 5 years or more. The elevated risk among short term users, if not due to residual confounding or selection mechanisms, is probably explainable in terms of recall bias (i.e. more careful report of short or very short use by cases). No definite pattern was observed in relation to latency or recency of use, and the point estimates were 0.8 for women who had ever used the pill before age 25 and 0.8 for those who had ever used the pill before first full-term pregnancy. Thus, the study presents further reassuring information on the oral contraceptive/breast cancer debate. Its major limitation lies in the low prevalence of oral contraceptive users in Italy, with a consequently reduced statistical power, although, with the number of cases involved, it was possible to exclude a relative risk of 1.4 for long-term use or for ever use before first birth. PMID- 2591455 TI - The relationship between treatment duration and temperature for hyperthermia induced lethality of cultured murine cells. Influence of medium conditions. AB - The heat sensitivity and the time-temperature relationship of non-tolerant and thermotolerant M8013 cells treated at different pHs in either culture medium (including serum) or Hanks' salts solution (HBSS) were compared. The cells were growing asynchronously. Arrhenius plots for non-tolerant cells heated in culture medium pH 7.35 showed two linear parts below and above the transition temperature (Ttrans). The inactivation energies below and above Ttrans were respectively 2980 and 490 kJ/mole. With thermotolerant cells under the same conditions the inactivation energy was approximately constant over the range 42-46 degrees C at 890 kJ/mole. The cells were more sensitive to heat treatment at low pH or in HBSS. Moreover, it appeared that the expression of thermotolerance was strongly dependent on medium conditions: the thermotolerance ratio (TTR, ratio between slopes of survival curves of thermotolerant and normal cells) was much lower at low pH or in cells heated in HBSS. Generally a high TTR observed in experiment with fractioned hyperthermia at temperatures above Ttrans correlated fairly well with a high inactivation energy below Ttrans from the Arrhenius plot derived from data from experiments with the same cells that were not made thermotolerant before treatment. PMID- 2591457 TI - Abstracts from the second annual meeting of the Danish Society for Cancer Research. 14 April 1989. PMID- 2591456 TI - Relapse from a stage IV-S neuroblastoma and N-myc amplification. PMID- 2591458 TI - Lack of effect of ponsinomycin on the plasma pharmacokinetics of theophylline. AB - The influence of ponsinomycin on the pharmacokinetics of theophylline has been studied in 12 young healthy volunteers. They received 10 doses of theophylline 200 mg every 8 h p.o., successively in the absence and then in the presence of ponsinomycin. This new macrolide, structurally related to midecamycin, was given in the therapeutic dose of 800 mg b.d. for 5 days, starting 2 days before the second phase of treatment with theophylline. The pharmacokinetic parameters of theophylline, calculated from its plasma concentration at steady-state, were not affected by the co-treatment. In particular, there was no significant difference between the peak and trough plasma levels, apparent clearance or apparent elimination half-life of theophylline in the absence and the presence of ponsinomycin. Only renal clearance was slightly (27%) but significantly increased by the co-treatment. The results suggest that ponsinomycin would be a good choice if a macrolide antibiotic were needed in patients being treated with theophylline. PMID- 2591459 TI - Effects of atenolol and pindolol on the hypokalaemic and cardiovascular responses to adrenaline infusion. AB - To investigate if the intrinsic sympathomimetic activity of pindolol could modify its beta-blocking effects on the responses to an adrenaline infusion, 10 healthy volunteers were studied. At an interval of 1-4 weeks each subject received pindolol and atenolol in randomized order before the infusion of adrenaline 0.06 microgram.kg-1.min-1. Pindolol prevented hypokalaemia and significantly decreased the heart rate during the adrenaline infusion. These effects were not observed after atenolol. The diastolic blood pressure was slightly increased during the infusion of adrenaline after pindolol, whereas it remained unchanged after atenolol. PMID- 2591460 TI - Double-blind plethysmographic study of venous effects of heptaminol adenosine phosphate in patients with primary varicose veins. AB - Changes in venous haemodynamics were studied after administration of a single dose of 3 g Heptaminol Adenosine Phosphate (HAP) to 30 subjects with primary varicose veins. Strain gauge plethysmography was used to observe changes in venous volume and in maximal venous outflow, 1, 2, 3 and 4 h after dosing. A significantly greater reduction in these parameters was found after treatment with HAP compared to placebo, indicating an improvement in lower limb venous circulation. PMID- 2591461 TI - Lymphocyte adenylate cyclase activity in immunosuppressed patients. AB - In order to determine whether alterations of adenylate cyclase are involved in the immunosuppressive effect of glucocorticoid/cyclosporin treatment we measured basal, prostaglandin E1-, and forskolin-stimulated cAMP production in lymphocyte membranes from kidney transplant patients undergoing glucocorticoid and/or cyclosporin A treatment. Healthy volunteers and hemodialysis patients with immunosuppression due to uremia served as controls. Whereas adenylate cyclase activity was similar in healthy and uremic controls, basal and stimulated activity were increased threefold in patients with immunosuppressive medication. We suggest that an activation of adenylate cyclase might be involved in the immunosuppressive effects of glucocorticoids and/or cyclosporin A. PMID- 2591462 TI - Interconversion between haloperidol and reduced haloperidol in healthy volunteers. AB - The interconversion between haloperidol (HAL) and reduced haloperidol (RHAL) was examined following their separate administration in low (5 mg) single oral doses to 15 young healthy male volunteers in a crossover design. Using an ultrasensitive HPLC method plasma concentrations of HAL and RHAL were monitored over a period of one week following each administration. Except in one case, both the analytes were found in the plasma of all the volunteers following each administration, thereby indicating interconversion of the two compounds. Comparison of the AUC(0-t) ratios of RHAL/HAL and HAL/RHAL following administration of HAL and RHAL, respectively, revealed that the interconversion favours the reduction of HAL to RHAL. The disposition of HAL following administration of RHAL appears to be limited by its rate of formation and the disposition of RHAL following administration of HAL, on the other hand, is much slower than that of the parent compound. PMID- 2591463 TI - Haemodynamic and pharmacokinetic evaluation of alfuzosin in man. A dose ranging study and comparison with prazosin. AB - In an open dose ranging study with random inclusion of placebo, alfuzosin (alpha 1-adrenoceptor antagonist) 1, 2.5 and 5 mg was administered to 6 healthy volunteers, 3 of the volunteers received 10 mg alfuzosin. Supine systolic blood (SBP) pressure was not reduced by alfuzosin although significant increases occurred in supine heart rate (HR) after 2.5 and 5 mg. In the standing position, SBP was reduced at 2 and 4 h with 5 mg alfuzosin; significant increases in HR occurred following 1, 2.5 and 5 mg at 2, 4, 6 and 8 h after administration. Exercise SBP was not reduced; diastolic blood pressure was significantly reduced at 4 and 6 h with 5 mg alfuzosin. More marked effects were seen in the 3 subjects who received 10 mg alfuzosin. After 1 and 5 mg, tmax ranged from 1-2 h; Cmax (4.1 to 20.8 ng.ml-1; AUC (0-24) 20 to 132 ng.ml-1.h (1 and 5 mg respectively) increased progressively with dose indicating dose dependent kinetics; no significant changes occurred in the visual analogue scale for sedation. A comparison of alfuzosin 5 mg, prazosin 1 mg and placebo each administered for 4 days, indicated that alfuzosin did not significantly reduce standing SBP on either Day 1 or Day 4; prazosin reduced SBP at 2 and 4 h on Day 1 and 6 h on Day 4 compared to placebo. Standing HR was increased by alfuzosin at 2 h on Day 1 and Day 4; increases occurred with prazosin at 2, 4, 6 and 8 h on Day 1 and 6 h on Day 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591464 TI - Metabolism and disposition of intravenously administered acetyl-L-carnitine in healthy volunteers. AB - The pharmacokinetics of acetyl-L-carnitine hydrochloride were investigated in 6 healthy volunteers of both sexes after i.v. injection of 500 mg of the drug, expressed as inner salt. Plasma concentrations and urinary excretion of acetyl-L carnitine (A), L-carnitine (B) and total acid soluble L-carnitine fraction were evaluated over a period lasting from 24 h before to 48 h after the administration. Plasma concentrations of A increased quickly after administration and then declined reaching base values within 12 h. Conversely, plasma concentrations of B rose more slowly, reaching a peak in 30-60 min, and then declined to base values within 24 h. Most of the injected dose of acetyl-L carnitine was recovered in the urine during the first 24 h after administration as B and A. Mean renal clearance of both A and B during the first 12 h after injection was higher than the base values, suggesting the presence of a saturable tubular reabsorption process which may counterbalance major changes occurring in plasma concentrations of L-carnitine pattern. PMID- 2591465 TI - Paediatric drug prescribing. A comparison of Tenerife (Canary Islands, Spain) and Sweden. AB - The prescribing of medicines for ambulant children below 14 years of age has been compared between Tenerife (Spain) and Sweden. Data obtained from a random sample of 1327 children in a prospective study in Tenerife were compared with data from 3901 children in a Swedish survey linking diagnosis and therapy. Upper respiratory tract infection was the main diagnosis in both countries and antibiotics was the most frequently prescribed drug group (28.2% in Tenerife and 28.8% in Sweden). Half of the children in Sweden did not receive any medication, but only 10% of those in Tenerife did not receive a prescription. Children who received a prescription on average got 1.4 drugs in Sweden and 2.3 in Spain. Amongst the ten most commonly prescribed products in Sweden there were 11 active pharmacological principles as compared to 25 in Spain. These most frequently used preparations accounted for two thirds of all the prescriptions for children in Sweden and one third in Tenerife. In conclusion, drugs were significantly more often used to treat paediatric outpatients in Tenerife than in Sweden. The prescribing physician in Spain also chose a wider variety of drugs and more commonly used fixed combination products. PMID- 2591466 TI - First dose and steady-state pharmacokinetics of oxcarbazepine and its 10-hydroxy metabolite. AB - The pharmacokinetics of oxcarbazepine (a new anticonvulsant which is a congener of carbamazepine) and of its 10-hydroxy metabolite were studied at the outset of therapy in 8 adult epileptics comedicated with other anticonvulsants. The pharmacokinetic study was repeated under steady-state conditions after 3 months of drug intake in 6 of these subjects. The plasma elimination half-life of oxcarbazepine appeared to lie in the range 1.0-2.5 h, and that of its 10-hydroxy metabolite averaged 8.4 h. The apparent oral clearance of the parent drug (averaging 2.51.kg-1.h-1) was high enough to suggest substantial presystemic elimination. The oral clearance fell after 3 months of drug intake, but the half lives of the drug and metabolite showed no statistically significant change over this time. Steady-state plasma levels of both drug and metabolite were linearly related to drug dose, metabolite levels averaging 9 times those of the parent substance. PMID- 2591467 TI - Influence of chronic diflunisal treatment on the plasma levels, metabolism and excretion of indomethacin. AB - The single-dose pharmacokinetics of indomethacin following 100 mg rectally was measured in two groups of 8 healthy subjects before and after diflunisal 500 mg p.o. once daily, or 500 mg in the morning and 1000 mg in the evening, until steady state conditions were reached. A further group of 8 healthy subjects was given 50 mg indomethacin rectally before and after diflunisal 500 mg p.o. twice daily. High dose diflunisal (1500 mg/day) decreased the renal clearance of indomethacin from 21.9 to 1.8 ml/min (92%) and reduced the renal excretion of both unchanged (63%) and conjugated (82%) indomethacin. The apparent total body clearance (0.12 l/h/kg), apparent volume of distribution (0.98 l/kg), and volume of distribution at steady state (0.80 l/kg) were decreased by 47%, 35% and 30%. The maximum plasma concentration (2.4 micrograms/ml) and total area under the curve (13.0 micrograms x h/ml) were increased by 40% and 119%, respectively. The terminal elimination half-life (5.7 h) and mean residence time (6.7 h) were slightly prolonged (7.0 h and 8.8 h) in the presence of diflunisal. The contribution of metabolism to the overall elimination of indomethacin was increased by only 2%. Similar results were obtained when the subjects were challenged with the low dose of diflunisal (500 mg/day), although the magnitude of the changes were smaller. The interaction between indomethacin and diflunisal may be due to competition both at the metabolic (conjugation) and the excretory (tubular secretion) levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591468 TI - The pharmacokinetics of low-dose dexamethasone in congenital adrenal hyperplasia. AB - The pharmacokinetics of dexamethasone, given at low dose, were studied in 13 patients with congenital adrenal hyperplasia (CAH) to ascertain whether kinetics differed in this inherited disorder of cortisol metabolism from those seen in healthy individuals. Changes in plasma dexamethasone concentration after intravenous bolus, measured using a simple novel radioimmunoassay, were well described by a two-compartment open model with first-order kinetics. Values for lambda 2: 0.206 h-1, t1/2: 3.53 h, Vc: 24.41 and f: 0.64 were similar to those previously reported for normal subjects. There were considerable interindividual differences in parameter values and Cmaxp.o. (range 22-67 nmol/l). As suppression of the hypothalamo-pituitary-adrenal axis correlates with plasma dexamethasone levels, this variability may partly explain the differing dose and dose schedule requirements necessary to achieve adequate therapeutic control in the clinical management of CAH. PMID- 2591469 TI - Zero-order absorption and linear disposition of oral colchicine in healthy volunteers. AB - The pharmacokinetics of colchicine has been studied in nine healthy male volunteers after oral doses of 0.5, 1, and 1.5 mg as tablets. Plasma and urine samples were collected over 48 h and analysed for colchicine by radioimmunoassay. Individual colchicine concentration profiles in plasma and urine were well described by a two-compartment open model with zero-order input. Considering the absorption variables as specific to each experiment, the lag time (0-0.35 h) and duration (0.39-2.38 h) of absorption were found to be independent of dose, while the zero-order rate constant of absorption (k0) increased linearly with dose. Disposition variables were taken as common to the three experiments, except in six subjects in whom renal excretion varied significantly across experiments in a dose-independent manner. For seven subjects the terminal half-life was 19.4 h, the oral apparent volume of distribution at steady-state (Vss/f) was 691 l, and the oral systemic clearance (CL/f) was 33.1 l.h-1. In the two other subjects, the values were unreliable, but the estimated terminal half-life was greater than 48 h, Vss/f ranged from 1690 to 3480 l, and CL/f was in the range of the other subjects in 1 subject, and it was about 15 l.h-1 in the other. In the latter subject, these estimates, together with the observation that plasma concentration reached a plateau at 2 to 5 h after ingestion, suggest enterohepatic cycling of colchicine. Overall, the disposition of colchicine was linear in the dose range 0.5-1.5 mg, with a long terminal half-life, and absorption obeyed zero-order kinetics, with k0 proportional to dose. PMID- 2591470 TI - Influence of hyperlipidic food on the kinetics of slow-release formulations of theophylline. AB - A cross-over study of kinetics has been undertaken in 12 healthy adults volunteers using two sustained-release theophylline products that allow once a day dosing (Theo-Dur tablets and Dilatrane A.P. bead filled capsules) to compare the i.v. pharmacokinetic profiles when taken with an hyperlipidic meal and a balanced standard meal. Each subject took part in four phases in randomised order, corresponding to all possible combinations of the products and the types of meal. Each phase involved a single dose of 9 to 11 mg.kg-1 theophylline administered at 20.00 h, at the beginning of the meal, with 100 ml water. The two formulations were found to be bioequivalent with both types of meal. Taken with a balanced meal, the mean parameters were similar; for Theo-Dur and Dilatrane A.P. they were respectively: Cmax: 11.32 mg.l-1 which plateaued from 8 to 10 h after dosing and 10.9 mg.l-1, which plateaued after 6 to 10 h; AUC 230 mg.h.l-1 and 220 mg.h.l-1; and MRT 18.2 h and 17.7 h. After the hyperlipidic meal the values for Theo-Dur and Dilatrane A.P. respectively, were: Cmax 10.9 mg.l-1 at 12 h and 11.3 mg.l-1 at 10 h; AUC 237 mg.h.l-1 and 227 mg.h.l-1; and MRT 19.2 h and 18.9 h. In spite of a decrease in the absorption rate, which led to a shift to the right of about 2 h of the plasma concentration-time curve, the bioavailability of both formulations were not significantly modified by a hyperlipidic meal as compared to a balanced meal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591471 TI - Inaccuracy in the doses of injectable medications dispensed from rubber-stoppered vials. AB - The literature of pharmacology often assumes that a full dosage is utilized when the contents of a vial have been administered by syringe. Five hundred discarded medication vials were assayed. The residues amounted to 1.98% to 8.81% of the listed dosages. An additional 0.7% to 8.66% remained in the syringes and needles used to aspirate the vials. Routine preparation techniques do not recover medication trapped on glass and rubber surfaces; losses are greatest when small diluent volumes are added to prepare intramuscular injections. The mean dose of gentamicin recovered from 80-mg ampules was 78.65 mg, and comparable vials of tobramycin yielded 76.01 mg. The discrepancy may contribute to the "increased toxicity" of gentamicin. Each year, more than $40,000,000 worth of antibiotics are lost to a biopharmaceutical dead space. Used antibiotic and controlled substance vials pose a potential threat to the environment. Although the amount of drug lost during preparation and administration may be of little therapeutic consequence, the discrepancy between intended and administered dosage is reflected in economic loss and pharmacological confusion. Pharmacological data should be adjusted for such losses. Medication wastage could be reduced by redesign of vials and alterations in practice of the administration. PMID- 2591472 TI - Effect of thiazide treatment on biliary lipid composition in healthy volunteers. AB - An increased incidence of cholecystitis has been observed in thiazide-treated patients. In order to test the possibility that the therapy might have caused an increase in the cholesterol saturation of gallbladder bile, biliary lipid composition was determined in fasting duodenal bile obtained from 10 healthy individuals after cholecystokinin injection, before and after 3 weeks of treatment with hydrochlorthiazide. The mean relative concentration of cholesterol was increased in 6 subjects, from 4.7 to 5.6 mol%, and the cholesterol saturation of bile was increased in 7, from 69 to 81%. These preliminary results indicate that thiazide treatment may to some extent increase biliary cholesterol saturation, and this may, at least in part, explain the higher prevalence of symptomatic gallbladder disease during such therapy. PMID- 2591474 TI - Brain and spinal cord 5-HT2 receptors of morphine-tolerant-dependent and abstinent rats. AB - The effects of morphine tolerance-dependence and abstinence on 5-HT2 receptors in brain and spinal cord of the rat were determined. Tolerance to and physical dependence on morphine was induced in male Sprague-Dawley rats by implanting six morphine pellets (each containing 75 mg of morphine free base) during a seven day period. Two groups of rats were used for binding studies. In one group the pellets were left intact and in the other they were removed. The rats were killed and spinal cords and brains were excised and dissected into six regions (amygdala, hippocampus, hypothalamus, striatum, midbrain and pons + medulla). 5 HT2 receptors were characterized by using [3H]spiperone as the ligand and unlabelled ketanserin to determine the non-specific binding. In morphine and placebo abstinent rats the binding of [3H]spiperone to 5-HT2 receptors in brain regions and spinal cord did not differ. The Bmax values of [3H]spiperone to bind to membranes prepared from non-abstinent morphine-dependent rats were increased in amygdala (78.0%), midbrain (65.0%) and pons + medulla (92.0%). The Kd values were unaffected. It is concluded that in morphine-tolerant-dependent rats 5-HT2 receptors are up-regulated in amygdala, midbrain and pons + medulla, but in morphine-abstinent rats they are unaffected. PMID- 2591475 TI - A Ca2+-activated K+ channel from rabbit aorta: modulation by cromakalim. AB - A large conductance Ca2+-activated K+ channel from rabbit aorta was incorporated into planar lipid bilayers. This channel had a conductance of 337 +/- 7 pS in symmetrical 250 mM KCl solutions and had a Na+/K+ permeability ratio of less than 0.04. In asymmetrical solutions containing 300 mM KCl cis (intracellular), 100 mM KCl trans (extracellular) or 100 mM KCl cis 500 mM KCl trans, the reversal potentials for the channel were -30 and +46 mV, respectively. This channel possessed voltage-dependent activation and cis (intracellular) Ca2+ sensitivity. Cromakalim (50 nM) added to the trans side of the bilayer significantly increased the Popen by 56% from 0.09 +/- 0.01 to 0.14 +/- 0.01 (P less than 0.01) at -40 mV without altering the single channel conductance. This effect was dose-dependent, increasing at higher cromakalim concentrations. The primary effect of cromakalim was to decrease the tau slow of the channel closed state from 266 +/- 32 to 147 +/- 17 ms which is sufficient to account for the increase in Popen of the channel in the presence of cromakalim. PMID- 2591473 TI - Sex-related differences in theophylline pharmacokinetics. AB - Theophylline pharmacokinetic parameters were compared in healthy males and healthy premenopausal females who were matched for age and smoking status. Twenty four subjects (including five smokers and seven non-smokers of each sex) received a single dose of aminophylline 6 mg.kg-1, orally or by intravenous infusion. Theophylline half-life was significantly shorter in female non-smokers (FNS) versus male non-smokers (MNS), (FNS = 6.0 h; MNS = 9.3 h), and in female smokers (FS) versus male smokers (MS), (FS = 4.6 h; MS = 6.3 h). Total body clearance was significantly different in FNS versus MNS, (FNS = 43.8 ml.min-1.-1(1.73) m-2; MNS = 37.4 ml.min-1.1.73 m-2), but did not reach statistical significance in FS vs. MS, (FS = 64.2 ml.min-1.1(-1).1.73 m-2; MS = 53.1 ml.min-1.1.73 m-2). Volume of distribution did not differ significantly between groups. Sex differences in theophylline pharmacokinetics exist and may reflect differences in drug metabolism. PMID- 2591476 TI - Capsaicin-sensitive vagal afferent fibers and stimulation of gastric acid secretion in anesthetized rats. AB - The sensory neurotoxin, capsaicin, has been used to study the reflex pathway by which gastric acid secretion increases in response to gastric distension in urethane-anesthetized rats. Capsaicin (1%) or vehicle (10% Tween 80 in olive oil) was applied directly to each cervical vagus 7-14 days prior to experiments. Gastric acid secretion was measured in acute gastric fistula rats by continuous intragastric perfusion and back titration or by flushing the gastric contents with saline every 10 min. Gastric acid secretion was stimulated by distension (5 ml for 6 min) or by injection of secretagogues (histamine 5.0 mg/kg s.c., bethanechol 0.5 mg/kg s.c. or pentagastrin 16 micrograms/kg per h i.v.). Gastric distension increased gastric acid secretion 6.2 times over basal gastric acid secretion in vehicle-treated control rats; capsaicin pretreatment significantly reduced this response by 40%. Bilateral cervical vagotomy significantly reduced the secretory response to gastric distension in the vehicle-treated group to a level not significantly different from capsaicin-treated rats. The secretory response to histamine was reduced by 42% in capsaicin-treated rats compared to vehicle pretreatment whereas the responses to pentagastrin and bethanechol were unaltered. These results indicate that capsaicin-sensitive vagal afferent fibers mediate the vagal portion of the secretory response to gastric distension; in addition these afferents play a role in the gastric acid secretory response to histamine. PMID- 2591477 TI - Effects of caffeine and doxapram perfusion on local cerebral glucose utilization in conscious rats. AB - The quantitative autoradiographic 2-[14C]deoxyglucose method was used to measure the effects of a continuous infusion of the respiratory stimulants, caffeine or doxapram, 18 mg/kg per h, on local cerebral glucose utilization in the adult male rat. Local cerebral glucose utilization was measured in 54 cerebral structures from different systems. Caffeine induced widespread increases in energy metabolism, resulting in a significant increase in glucose utilization in 25 structures out of the 54 studied. These increases were distributed within all systems studied, sensory, extrapyramidal motor, limbic and hypothalamic systems. In addition, caffeine induced a non-significant, 10-15%, increase in local cerebral glucose utilization in central respiratory areas. Doxapram infusion did not change the rates of glucose utilization in any of the structures. The rates of local cerebral glucose utilization were significantly lower after doxapram than after caffeine exposure in five cerebral areas, among which were three central respiratory areas. The results confirm the absence of side-effects of doxapram as compared to caffeine when used as respiratory stimulant, especially in neonates. These results also favor a preferentially central action of caffeine on respiratory areas and a more peripheral action of doxapram on chemoreceptors, at least at therapeutic levels. PMID- 2591478 TI - A comparison of the relaxant effects of pinacidil in guinea-pig trachea, aorta and pulmonary artery. AB - The relaxant activity of pinacidil, a proposed K+ channel opener, was compared in isolated guinea-pig trachea, aorta and pulmonary artery. In preparations precontracted by histamine or PGF2 alpha, pinacidil produced complete tracheal relaxation but only partial relaxation of vascular tissues. The order of responsiveness was: pulmonary artery greater than trachea greater than aorta. The slope of the pinacidil concentration-effect (C/E) curve was much steeper in the tracheal than in the vascular preparations. The pinacidil C/E curves for relaxation were similar when the three types of preparations were precontracted by 124 mM K+. Pretreatment with pinacidil caused a parallel shift of the tracheal histamine C/E curve to the right, whereas the maximal response to histamine was markedly depressed in the pulmonary artery. PMID- 2591479 TI - Chronic electroconvulsive shock increases D-1 receptor binding in rat substantia nigra. PMID- 2591480 TI - The putative 5-HT3 agonist phenylbiguanide induces carrier-mediated release of [3H]dopamine. PMID- 2591481 TI - Symptoms of craniomandibular disorder in a sample of Finnish adolescents at the ages of 12 and 15 years. AB - Subjective symptoms of craniomandibular disorder (CMD) were studied longitudinally in 167 children at the ages of 12 and 15 in order to investigate their importance for orthodontic diagnosis. The results showed that symptoms are quite common in adolescents (64-67 per cent). However, most of the adolescents experienced their symptoms only occasionally. Frequent occurrence of various, single symptoms of CMD varied from 0 to 7.2 per cent. Recurrent headache was reported by 24 per cent of the adolescents at the age of 12, and by 22 per cent of them at the age of 15. The number of reported symptoms did not increase between the ages of 12 and 15 years, which is in agreement with other studies. The symptoms of CMD did not appear to be consistent. Locking of the joint was found to be the most stable symptom. About 50 per cent of those reporting TMJ clicking, unexplainable ear symptoms or bruxism at the age of 12, had lost this symptom by the age of 15. For pain on mouth-opening, the symptom group at the age of 15 consisted of entirely new individuals. Because of their inconsistent nature during the final stages of occlusal development, too much attention should not be paid to single occurrences of CMD symptoms. In individual cases, however, important information for diagnosis and treatment planning can be obtained. Symptoms of craniomandibular disorder, recurrent headache, and oral parafunctions should be elicited and recorded at annual dental check-ups of children and adolescents. PMID- 2591482 TI - Mandibular incisor stability after orthodontic treatment in the upper arch. AB - The aim of this study was to observe longitudinally the anterior region of the lower jaw when treating only the upper jaw. A comparison was made between a group of 35 children treated with extraction of the maxillary first premolars and a fixed appliance in the upper jaw and a control group of 19 untreated children. The treatment group was studied with plaster models on five occasions: before treatment, at the end of active treatment, at the end of retention, after one year out of retention and at the last registration, in total over about a seven year period. Cephalometric registrations were made before treatment and at the last registration. The control group was studied with plaster models and lateral head films during a period of nine years and their age at the last registration was the same as for the treatment group. The space loss in the anterior region of the lower jaw increased from a mean of 0.4 mm (s.d. 0.82) to 2.5 mm (s.d. 1.52) in the treatment group and from 0.1 mm (s.d. 0.16) to 0.5 mm (s.d. 0.81) in the control group: an extra space loss of 2.0 mm for the treatment group. The main increase was registered during treatment and after retention. Subjective ranking of the plaster models from the final registrations according to the amount of crowding in the lower anterior region also showed a significant difference between the treatment group and the control group, the treatment group showing the largest of crowding. In cases where maxillary protrusion is treated by extraction in the maxilla only, stabilization of the lower arch with fixed orthodontic appliances seems justified. PMID- 2591483 TI - Changes in the pharyngeal airway in relation to extension of the head. AB - In a sample of 20 adults the associations between cervical lordosis, craniocervical inclination, position of the hyoid bone and cross-sectional dimensions of the pharyngeal airway were studied. Lateral skull radiographs were obtained in natural head posture and also at 20 degrees extension with the subjects' teeth in the intercuspal position. Cervical lordosis was measured from the second to the sixth vertebra and the position of the hyoid bone was calculated in horizontal and vertical directions. The dimensions of the free airway were measured between the dorsal tongue surface and the posterior pharyngeal wall and at the level of the second and fourth vertebra. A change from natural head posture to 20 degrees extension resulted in an increase in cervical lordosis and craniocervical inclination, changed position of the hyoid bone and increased cross-sectional dimensions of the pharyngeal airway. The changes in lordosis produced by changing natural head posture to 20 degrees extension showed significant correlations with the size of changed craniocervical inclination and free airway. PMID- 2591484 TI - Effects of sagittal split advancement osteotomy on facial profiles. AB - In 31 surgically treated Class II patients, several features were studied on cephalograms, before and after a mandibular lengthening osteotomy had been performed. After surgery, hardly any changes in the soft tissue thickness were recorded. In Class II patients, the upper part of the lower lip is situated at a larger distance from the skull, since its position is influenced by the antero posterior position of the upper incisors and the overjet. The postoperative decrease of this distance was caused by the fact that the upper part of the lower lip failed to follow the total amount of forward mandibular displacement. This is due to the fact that the antero-posterior position of this part of the lip is touching the upper incisors and therefore does not follow the amount of mandibular advancement. The labiomental fold flattens, because the lower part of the lower lip completely follows the forward displacement of the mandible, whereas the upper part remains almost unchanged. This flattening can be favourable in Class II patients showing a very deep fold, as the surgical intervention tends to normalize the depth. In open bite profiles on the contrary, this effect could be unfavourable. The combination of the lengthening osteotomy with a genioplastic intervention, could mask this unfortunate result. Due probably to the presence of orthodontic retention devices and the intercuspidation of teeth, normal occlusal relations remained one year after surgery. A relapse of about 30 per cent was found in the mandibular bases. In order to anticipate this, some surgical overcorrection could be considered. PMID- 2591485 TI - Profile changes following orthodontic treatment of bimaxillary protrusion in adults with the Begg appliance. AB - Thirty-two adult oriental patients aged 18-26 years who sought treatment for their bimaxillary protrusion were treated with the Begg appliance following extraction of four first premolars. A cephalometric study was undertaken to determine the soft tissue changes in lip profile following treatment. Results show that the upper incisors were retracted by 5.6 mm +/- 0.8 mm and the lower incisors by 4.4 +/- 0.8 mm on the average. The nasolabial angle became more obtuse increasing from 80.7 degrees to 90.7 degrees. The upper lip and lower lip lengthened by 1.9 mm and 1.2 mm, respectively. The lower lip to 'E' line reduced from 7.5 mm to 3.7 mm. All the previous changes were statistically significant (p less than 0.01). The upper lip to upper incisor retraction was 1:2.2 while the lower lip to lower incisor retraction was 1:1.4. The correlation coefficients (r) were 0.72 (p less than 0.01) and 0.80 (p less than 0.01), respectively. The changes in the cants of mandibular and occlusal planes were statistically insignificant. This study shows that the Begg appliance has the ability to significantly reduce bimaxillary protrusions and thereby improve facial aesthetics. PMID- 2591486 TI - Effects of directions of maxillary protraction forces on biomechanical changes in craniofacial complex. AB - The purpose of this study was to investigate the effect of directions of extraoral maxillary protraction forces on biomechanical changes in the craniofacial complex, using the three-dimensional finite element method (FEM). A three-dimensional FEM model was developed on the basis of a young, human dry skull. The model consisted of 2918 nodes and 1776 solid elements. An anteriorly directed 1.0 Kg force was applied to the buccal surface of the maxillary first molar in directions varying from -90 to 90 degrees to the occlusal plane. The displacement pattern of the entire craniofacial complex was evaluated. Further, the stress distributions were determined in three transverse planes associated with parallel, and 30 degrees upward and downward forces. As the force direction was more upward, repositioning of the craniofacial complex became larger in both the horizontal and vertical directions. Displacements were most translatory in loading with the forces applied in the directions ranging from -45 to -30 degrees to the occlusal plane. High stress levels were observed in the nasomaxillary complex and its surrounding structures. However, the patterns of stress distribution within the complex were different for three loading conditions. A downward protraction force produced the most uniform stress distribution. It is shown that the force direction plays an important role in determining the repositioning and the stress distributions in the craniofacial complex. PMID- 2591487 TI - Herbst treatment in late adolescence: clinical, electromyographic, kinesiographic, and radiographic analysis of one case. AB - In an almost full-grown male of 17 years, functional and morphological changes were followed during Herbst treatment and subsequent control. Retrognathism of the mandible was overcorrected, and then normalized by reverse headgear to the maxilla. Partial relapse due to insufficient cooperation during retention necessitated retreatment. Treatment resulted in marked dentoalveolar changes, increase in mandibular length and ramus height, apposition and remodelling of condylar heads and flattening of the temporal joint surface. After treatment masseter strength was 40 per cent reduced, probably due to prolonged hypofunction. PMID- 2591488 TI - Dentition in children with enlarged tonsils compared to control children. AB - The aim of the present study was to evaluate whether or not there are any differences in the dentition between children with enlarged tonsils and those with normal tonsils. A sample of 73 children (33 boys and 40 girls) with enlarged tonsils and with a mean age of 10.1 years was compared with a normal control group, matched for age and sex. Eighteen dentition variables and thirty-two variables in anamnestic, clinical, pharyngeal and postural findings were recorded. Measurements were obtained from lateral skull radiographs and dental casts. Group means were compared. Relationships between variables were studied using simple correlations and multiple stepwise regression analyses. It was found that children with enlarged tonsils had more retroclined lower incisors, more anteriorly positioned upper incisors, smaller overbite, larger overjet, shorter lower dental arches, narrower upper dental arches and an increased frequency of lateral crossbite. Functional and/or morphological disorders, causing an open posture of the mouth, a lowered anterior posture of the tongue and a low position of the hyoid bone are thought to be associated with the differences in the dentition between the two groups. Obstruction of the oropharynx by enlarged tonsils, might be one factor responsible for these dysfunctions. PMID- 2591489 TI - Filipin-induced deformations in plasma membranes of cultured bovine corneal endothelial cells with incomplete belts of tight junctions. AB - Complete belts of intact tight junctions are thought to act as barriers to the movement of cholesterol in the plane of the plasma membrane. As cholesterol can be revealed by filipin-induced membrane deformations on freeze-fracture images, we studied the distribution of these deformation in cultured bovine corneal endothelial cells with incomplete belts of tight junctions. While the extent of filipin-induced deformations differed between individual cells, there is a homogeneous distribution of filipin-induced deformations on both sides of the incomplete junctional belt of endothelial cells. Our results suggest that cultured endothelial cells do not polarize cholesterol, possibly because of the incomplete tight-junctional barrier. PMID- 2591490 TI - Experimental bacterial endophthalmitis following extracapsular lens extraction. AB - The rapid increase in popularity of extracapsular cataract extraction may predispose the eye to postoperative bacterial infections by introducing viable organisms through the additional instrumentation and irrigation necessary for the extracapsular technique. Lens protein released into the aqueous humor of the anterior and posterior chambers may enhance or inhibit the ability of organisms to grow in the aqueous humor. In the intact eye the lens acts as a significant protective barrier restricting the posterior extension of the infectious processes. This study was undertaken to determine if extracapsular lens extraction enhances the ability of common bacteria to infect the anterior segment of the eye and if the posterior lens capsule acts as a protective barrier denying the infectious process access to the vitreous body. Approximately 1000 colony forming units (CFU) of Staphylococcus aureus were required to produce bacterial endophthalmitis in less than one-half of normal rabbit eyes and eyes following extracapsular lens extraction. Discission of the posterior lens capsule tripled the number of eyes infected. As few as fourteen CFU could produce infections in some eyes if the posterior capsule was incised. Extracapsular lens extraction does not predispose the eye to bacterial endophthalmitis if the posterior lens capsule remains intact. Interruption of the posterior lens capsule does allow a small number of organisms to establish an intraocular infective process. Lens protein and other constituents released into the aqueous humour appear to have little effect on the growth of the test organisms. PMID- 2591491 TI - Reversal of the epinephrine stimulation of Cl- transport in bullfrog cornea by phorbol esters. AB - The effects of protein kinase C (PKC) stimulation with phorbol dibutyrate, PDBu, were determined on transepithelial net Cl- transport (Isc) across the isolated bullfrog cornea. Between 1 nM and 1 microM, PDBu had no effect on either the Isc or the conductance, gt, as well as the membrane voltage (Vsc) but it decreased the fractional apical membrane resistance (fR0). PDBu caused a dose-dependent decline and reversal of the stimulatory effect of the mixed alpha and beta adrenergic agonist, epinephrine, on the Isc. With 1 microM PDBu, 100 microM epinephrine decreased the Isc by 20% below its control value. As without PDBu, epinephrine decreased fR0 and depolarized the Vsc. Evidence that this reversal by PDBu stems from a selective stimulation of PKC is: (1) neither its vehicle nor the inactive phorbol analog, 4 alpha-phorbol didecanoate, PDD (1 microM), decreased either the fR0 or altered the stimulatory effect of epinephrine on the Isc. (2) After preincubation with 30 microM H-7, which inhibited PKC stimulation in subcellular membrane and cytosolic fractions of frog corneal epithelium, the stimulatory effect of epinephrine on the Isc was unchanged by 1 microM PDBu. Preincubation with PDBu completely inhibited the stimulatory effect of the beta adrenergic agonist, isoproterenol (10 microM), on the Isc but did not affect the stimulatory effect of 1 microM forskolin on the Isc, indicating that PKC stimulation results in uncoupling of adrenergic regulation of adenylate cyclase activity. Epinephrine did not reverse the Isc in corneas that were preincubated with either the alpha 2- -adrenergic antagonist, yohimbine (100 microM), or the general alpha adrenergic antagonist, phenoxybenzamine (100 microM). With yohimbine, epinephrine had no effect on the Isc whereas with phenoxybenzamine the stimulation by epinephrine was fully restored. These effects suggest that stimulation of PKC is dependent upon the stimulation of alpha 1-adrenergic receptors by epinephrine as well as the presence of PDBu. Reversal and stimulation of the Isc by epinephrine were both associated with a depolarization of the Vsc and similar decreases in fR0. These similar effects on fR0 suggest that PKC stimulation as well as alpha 2 adrenergic activation by epinephrine are associated with increases in basolateral membrane resistance. PMID- 2591492 TI - In vitro corneal endothelial permeability in rabbit and human: the effects of age, cataract surgery and diabetes. AB - Endothelial permeability was examined in rabbit and human corneas using an in vitro perfusion system with 5(6)-carboxyfluorescein as the permeability tracer. Following endothelial removal, the permeability of de-epithelialized rabbit corneas increased from 3.19 x 10(-4) cm min-1 to 31.21 x 10(-4) cm min-1, and de epithelialized human donor corneal permeability values increased from 2.26 to 12.85. In human corneas, no correlation was seen between endothelial permeability and donor age, moist chamber storage time, endothelial cell density, coefficient of variation of cell area, or percent hexagonal cells. A positive correlation was found between permeability and time between donor death and enucleation. Donor eyes from three separate populations, having undergone cataract surgery prior to death (aphakic, posterior and anterior chamber implants), all showed a significant increase in permeability. Neither Type I nor Type II diabetes had an effect on the endothelial permeability of human donor corneas. PMID- 2591493 TI - Hard contact lens-induced metabolic changes in rabbit corneas. AB - The biochemistry of contact lens-cornea interaction is not well understood, although previous studies have suggested that corneal metabolic changes may be the underlying factor in morphological alterations. Using a rabbit model, this interaction has been examined with 31P nuclear magnetic resonance (NMR) spectroscopy, which detects signals principally from the epithelium. The examination was supplemented with electron microscopy and histochemistry. Polymethylmethacrylate lenses caused reversible changes, including activation of anaerobic glycolysis and disturbance of membrane metabolite levels. These changes were far more severe than those occurring during prolonged eye closure. There appears to be an association between cellular deterioration and loss of membrane metabolites. On the other hand, oxygen-permeable silicone lenses allowed maintenance of nearly normal metabolic patterns. These results show multifaceted corneal response to hard contact lens wear. PMID- 2591494 TI - Effects of 2-amino-4-phosphonobutyric acid (APB) and glycine on the oscillatory potentials of the rat electroretinogram. AB - Oscillatory potentials of the electroretinogram were monitored in dark-adapted rats following intravitreal injection of 2-amino-4-phosphonobutyric acid (APB), a glutamate analog that preferentially blocks the light response of depolarizing bipolar cells, or glycine, a known endogenous inhibitory neurotransmitter that suppresses the light response of cells in the inner retina postsynaptic to glycinergic neurons. Oscillatory potentials were abolished in conjunction with the b-wave with APB and selectively reduced or eliminated by glycine: neither agent attenuated the a-wave. The results are compatible with the idea that light induced depolarizing bipolar cell, hyperpolarizing bipolar cell, and glycinergic amacrine cell responses are all necessary for the generation of oscillatory potentials in the rat. The results also suggest that hyperpolarizing bipolar cells do not contribute to b-wave generation. PMID- 2591495 TI - Variations in the severity of retinopathy seen in newborn rats supplemented with oxygen under different conditions of hyperbarism. AB - The purposes of this experimental study were to evaluate the effects of oxygen supplementation delivered under hyperbaric conditions on the retinas of newborn rats and to determine the minimum and maximum levels of hyperbarism capable of protecting the retinal vessels from the toxic effects of oxygen without determining lethal effects in this experimental model. A control group of newborn rats were maintained with their mother for the first 12 days of life under room air conditions. A second group of animals were exposed to a hyperbaric environment (+81 kPa) under normoxic conditions for the first 7 days of life and subsequently returned to normobaric conditions for the next 5 days. Examination of the retinal flat mounts from this latter group of animals revealed essentially normal vascular networks with only a modest degree of vasoconstriction. Two other litters of ratlings, with their mothers, were given supplemental oxygen at an FiO2 of 80% under a compression pressure of +101.25 kPa. In this group of animals, death of both of the mother rats from pulmonary edema occurred on the first day of treatment, and, in spite of immediate mother substitution, the newborn rats succumbed to the same complication. Five other groups, each containing two litters of newborn rats with their mothers, were exposed to FiO2s of 80% at hyperbaric levels ranging from +20.25- to +81.0 kPa for the first 7 days of life. On the eighth day, the FiO2s were reduced to 21%. After 5 days of room-air recovery, the animals were killed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591496 TI - Phosphatic metabolites in keratoconus. AB - Sixteen corneal buttons were obtained from 16 patients with keratoconus at the time of penetrating keratoplasty (mean age, 34 +/- 3.2 yr) and prepared for phosphorus-31 nuclear magnetic resonance spectroscopy following perchloric acid extraction. The corneas were compared with age-matched corneas from fresh eye bank eyes with normal slit-lamp biomicroscopic appearance. Higher levels (P less than 0.05) of nucleoside monophosphates and choline phosphate and lower levels (P less than 0.05) of adenosine diphosphate were detected in keratoconus than in eye bank corneas. The level of an unidentified metabolite at 3.96 delta, present in eye-bank corneas, was ninefold higher in keratoconus corneas. Another unidentified metabolite at 3.31 delta, accounting for 1.5% of the total detected phosphatic metabolites, appeared in keratoconus but not in eye-bank cornea spectra. These findings of altered phosphatic metabolites are consistent with altered corneal metabolism. The unidentified, unknown metabolites in the spectral profile uniquely distinguish keratoconus from eye-bank corneas. PMID- 2591497 TI - Physiological state of the rabbit cornea following 4 degrees C moist chamber storage. AB - Eyes from female albino rabbits (1.9-2.3 kg) were enucleated immediately following euthanasia along with the lids and conjunctiva. The globes were moist chamber-stored (in a 4 degrees C refrigerator with the lids closed and the cornea facing downwards) for 12-500 hr. Central corneal thickness (by ultrasound) increased from 350 to approximately 650 microns within 72 hr but changed little thereafter. In the latter period, the relative fluid pressure of the globe (pneumatonography) dropped to less than 10 mmHg, aqueous bicarbonate (tCO2) levels fell to less than 5 mM and anterior chamber fluid tonicity decreased progressively (especially after 24 hr storage) to reach values of around 200 mosmol l-1 by 7 days. Storma-endothelium preparations of the corneas, after 2 hr of in vitro equilibration with a bicarbonate-Ringer solution (supplemented with glucose, adenosine and glutathione) were evaluated for their ability to undergo deturgescence under silicone oil or to pump fluid against a hydrostatic pressure of 20 cmH2O. Corneal preparations from up to 7 days storage showed rapid (60 to 135 microns hr-1) and complete deturgescence (net change in thickness of 140-180 microns) that was maintained. Thereafter, the ability to show deturgescence declined to zero by 10 days. In marked contrast, endothelial fluid pump activity (of approximately 5 microliters hr-1) was manifest for only 36 hr after which time this function rapidly declined. Most corneas stored for periods longer than 48 hr exhibited a continuous leak (of -1 to -5 microliters hr-1). The results indicate that corneal deturgescence and endothelial fluid pump function are not necessarily coupled in vitro. PMID- 2591498 TI - Interphotoreceptor retinoid-binding protein (IRBP) in the postnatal developing rds mutant mouse retina: EM immunocytochemical localization. AB - The distribution of IRBP was examined in postnatal developing retinas of rds (020/A) mutant mice and Balb/c controls by EM immunocytochemistry. Light labeling for IRBP was detected in mutant and control retinas by postnatal day 9 (P9) largely in the interphotoreceptor matrix (IPM). At P14, some photoreceptors in the rds retina showed a higher density of label in the Golgi for IRBP than neighboring cells and those of controls processed simultaneously. This high density of label for IRBP was observed also in the Golgi of a small population of photoreceptor cells at P18, P19 and P21 in rds retinas. These cells were found to represent approximately 3-5% of the photoreceptor population. The density of label for IRBP at the apical RPE region was obviously low in the rds retinas by P18, P19 and P21. However, this same region in controls of the same ages was densely labeled for IRBP. The low density of labeling at the apical RPE region in the rds retinas may indicate a change in the rate of synthesis, secretion, distribution and/or degradation in the IPM. The high density of intracellular labeling in a small population of cells may be indicative of impaired secretion, an increase in IRBP synthesis or the initiation of photoreceptor deterioration. Whether the differences observed in the distribution of IRBP in the rds mutant are primary or secondary effects of the genetic lesion remains undetermined. PMID- 2591499 TI - Rhodopsin levels and rod-mediated function in Abyssinian cats with hereditary retinal degeneration. AB - Abyssinian cats with different stages of a slowly progressive autosomal recessively-inherited retinal degeneration were studied with imaging fundus reflectometry (IFR) and electroretinography (ERG). Maps of the visual pigment distribution were made in an area of retina extending from the posterior pole to the midperiphery. Rhodopsin levels in the midperipheral retina of a 6-month-old affected cat (stage of suspected disease) were reduced about 20% relative to the mean normal value. The same cat, tested at 2.5 yr of age (now moderately advanced stage), showed a 60% reduction. A 3-yr-old affected cat (also moderately advanced) had a reduction in rhodopsin of about 60%. There was no measurable rhodopsin in a 7-yr-old affected cat (advanced stage). Rhodopsin regeneration kinetics at the different stages of disease were found to be similar to those of normal cats. The rod ERG b-wave threshold in the 6-month-old cat was elevated by 0.26 log units; at 2.5 yr of age, the threshold was elevated by 0.48 log units. A 0.34 log units threshold elevation was found in the 3-yr-old cat. There was no detectable ERG in the 7-yr-old cat. The relationship between the rod ERG threshold elevations and the rhodopsin levels was close to that expected if the dysfunction was caused by decreased quantal absorption. PMID- 2591500 TI - Structural conversions of crystallins under senile cataract, dehydration and UV irradiation studied by X-ray diffraction. AB - By means of X-ray diffraction analysis, structural conversions of crystallins in human lens were detected in senile cataract and upon artificial dehydration of lens tissue. In senile cataract certain characteristics of the native three dimensional structure of gamma- and beta-crystallins are completely lost, whereas during dehydration of lens tissue a small but significant contraction of these protein molecules takes place. Upon artificial UV-irradiation of bovine crystallins destructive changes are observed, which are very similar to those in cataract. PMID- 2591501 TI - Keratoconjunctivitis sicca with associated secondary uveitis elicited in rats after systemic xylazine/ketamine anesthesia. AB - The systemic administration of an anesthetic dosage of a combination of xylazine and ketamine hydrochloride produced an acute exposure keratopathy which progressed into a syndrome resembling keratoconjunctivitis sicca. Within a few minutes corneal changes occurred that were characterized by viscous mucus, loss of corneal luster and dryness. Other acute but transient changes included development of cataracts, mydriasis and proptosis. Progressive changes were observed in the cornea within 4 days which lasted at least 8 weeks in some cases, and included punctate epithelial keratopathy progressing to devitalized or keratinized epithelial plaques. Polymorphonuclear cell infiltration of the corneal stroma associated with plaques occurred. Epithelial denudation and neovascularization of the cornea, dilation and engorgement of iridial blood vessels, as well as flare in the anterior chamber were also seen. The ocular lesions induced by xylazine/ketamine should be considered carefully when designing or interpreting research on the anterior segment. Ketamine hydrochloride with sodium pentobarbital produced excellent anesthesia without any significant ocular side-effects and may be preferred in many instances. PMID- 2591502 TI - Active transport of ascorbic acid into lens epithelium of the rat. AB - The transport rates of radiolabeled ascorbic acid (AA) and dehydroascorbic acid, as well as 3-O-methyl-D-glucose and L-glucose from blood into aqueous humor, lens epithelium and lens 'cortex' compartments were studied in male Sprague-Dawley rats. In vivo pulse chase kinetic studies and modeling of transport from plasma and aqueous and on into idealized water compartments of lens epithelium and cortex allowed for the calculation of transport rate constants, Ki (min-1), in experiments utilizing L-glucose as a passive internal control. TLC chromatography was used to monitor intraocular labeled molecules deriving from labeled test molecules introduced via blood. Results indicate that AA enters aqueous humor at rates similar to L-glucose and likely via simple passive diffusion. In contrast, an active uptake of AA by lens epithelium was found with the calculated entry constant for ascorbate being more than 21 times faster than that of L-glucose. Concentrations in lens epithelium were found to be more than twice that of aqueous humor within only 7 min from the introduction of a [14C]AA bolus into blood. It was also found that very little AA continued on past the epithelium to the interior lens cortex compartment. Our data suggest no special uptake of AA by lens fiber cells. The non-metabolizable analog of D-glucose, 3-O-methyl-D glucose, however, readily moves past the lens epithelium into fiber cells at much faster rates than the passive L-glucose marker and in a manner consistent with facilitated diffusion. The data suggest that even in a nocturnal species, such as a rat, which demonstrates relatively low circulating levels of ascorbic acid in plasma and aqueous humor, special mechanisms exist for moving ascorbic acid into intraocular tissues. More specifically, the lens epithelium actively takes up ascorbate for some, as yet unclear purpose while the interior fiber cells appear to have no special uptake mechanism for this molecule. PMID- 2591503 TI - Disulfide cross-linking of urea-insoluble proteins in rabbit lenses treated with hyperbaric oxygen. AB - In vivo exposure of human patients and experimental animals to hyperbaric O2 has been shown by other investigators to lead to opacification of the lens especially in the nuclear region. In the present study, cultured rabbit lenses were treated with hyperbaric O2 in order to investigate possible formation of disulfide-cross linked proteins in the urea-insoluble fraction of lens cortex and nucleus. When lenses were treated with 100 atmospheres of 100% O2 for 24 hr. intermolecular disulfide-linked proteins formed in both the cortical and nuclear regions. Under these conditions the level of reduced glutathione and the activity of glyceraldehyde-3 phosphate dehydrogenase (G-3PD) were depleted by greater than 95% in both regions. The lenses were hazy in appearance but not opaque. Two dimensional diagonal electrophoresis followed by immunoblotting indicated that the majority of the cross-linked proteins were beta- and gamma-crystallins. Also involved in the cross-linking was the enzyme G-3PD but not the main intrinsic membrane protein. MIP26 kDa. Treatment of the nuclear urea-insoluble fraction of O2-treated lenses with sodium borohydride showed a nearly fourfold increase in the level of protein disulfide compared to that present in the same fraction of either fresh lenses or N2-treated controls. It was determined that an increase of approximately one disulfide group per 10(5) Da molecular weight corresponded to cross-linking of nearly 20% of the urea-insoluble protein present in the O2 treated lenses. Experiments carried out at 8 atmospheres O2 were used to determine the region of the lens in which urea-insoluble disulfide first formed after exposure to O2. After 8 hr of treatment of lenses with 8 atmospheres O2 an increase in protein disulfide was observed in the urea-insoluble proteins of the lens nucleus but not of the cortex. Under these conditions, the level of glutathione had decreased by 62% in the nucleus compared to only 13% in the cortex. Increasing the culture time to 16 hr under 8 atmospheres O2 produced a further increase in protein disulfide in the nuclear region. The formation of a small amount of cross-linked protein in the cortex and a significantly greater decrease of G-3PD activity in the lens nucleus compared to the cortex. The overall results of the study demonstrate that exposure of lenses to hyperbaric O2 leads to disulfide-cross-linking of crystallins in the urea-insoluble fraction and that the initial formation of protein disulfide as well as the initial loss of glutathione occurs first in the lens nucleus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2591504 TI - Phosphorylcholine and phosphorylethanolamine in human and rhesus monkey lenses. AB - Phosphorylcholine (P-choline) and phosphorylethanolamine (P-ethanolamine) are important precursors of phospholipids. The metabolism and concentration of P choline has been shown to change in animal models of cataract, especially in oxidatively or osmotically stressed rat lenses. The concentrations of P-choline and P-ethanolamine were determined in monkey lenses and in normal and cataractous human lenses, and the rate of synthesis of P-choline was determined in human and monkey lenses. The concentration of P-choline in 53 clear human lenses was 0.94 mM (+/- 0.31 S.D.) and was relatively unaffected by age, eye bank storage, or freezing. There was a 70% decrease in P-choline in brown cataracts but no significant change from normal in non-brown cataracts. The concentration of P ethanolamine in human lenses was 0.45 mM (+/- 0.26 S.D.), and it appeared to decrease during frozen storage of lenses and in cataracts. The concentrations of P-choline and P-ethanolamine in 12 rhesus monkey lenses were 1.51 mM (+/- 0.27 S.D.) and 0.75 mM (+/- 0.14 S.D.), respectively. The rate of synthesis of P choline in monkey lenses incubated with [3H]choline was 8 nmol hr-1 g-1 wet weight in 1 mM choline. Adult human lenses incubated in 1 mM choline synthesized P-choline at a rate of 23 nmol hr-1 g-1 (+/- 6 S.D.). This limited capacity for P choline synthesis in primate lenses may contribute to the lower P-choline concentration relative to rat lenses, which contain 11 mM P-choline and can synthesize P-choline at an apparent maximum rate of 130 nmol hr-1 g-1. PMID- 2591505 TI - Local circuit neurons in both the dentate gyrus and Ammon's horn establish synaptic connections with principal neurons in five day old rats: a morphological basis for inhibition in early development. AB - Glutamate decarboxylase (GAD)-positive and Golgi impregnated local circuit neurons of the hippocampal formation of five day old rats were examined in light and electron microscopic preparations. The ultrastructural features of these neurons were similar in both the dentate gyrus and CA1 area of Ammon's horn. Somata displayed a perikaryal cytoplasm rich in organelles but lacked organized Nissl bodies. Most nuclei showed intranuclear infoldings of varying degrees but no intranuclear sheets or rods were found. Somata and dendrites were contacted by relatively immature axon terminals that formed mainly symmetric synapses. The axons of local circuit neurons in both the dentate gyrus and Ammon's horn formed symmetric synapses with somata and dendrites of the principal neurons in these regions. Thus, both GAD-positive and Golgi-impregnated terminals of local circuit neurons were observed to form synapses with pyramidal and granule cells. These terminals were usually small and contained relatively few pleomorphic synaptic vesicles. The results show that a circuitry for inhibition is established in the 5 day old dentate gyrus and Ammon's horn, even though the local circuit neurons lack some of the typical adult ultrastructural features at this age. PMID- 2591506 TI - Facilitation of quadriceps motoneurones by group I afferents from pretibial flexors in man. 1. Possible interneuronal pathway. AB - The neuronal pathway of the facilitation of quadriceps (Q) motoneurones (MNs) evoked by stimulation of the common peroneal nerve (CPN) has been reinvestigated using both the post-stimulus time histogram (PSTH) method for measurement of the firing probability of individual units and the H reflex technique. It has been found that Ia (and to an unknown extent Ib) afferents from pretibial flexors - but not from peroneal muscles - are responsible for this excitation. The central latency of the CPN-induced excitation of Q MNs was estimated to be 3-3.7 ms longer than that of their monosynaptic Ia excitation. To further investigate the neuronal pathway of the CPN-induced excitation the spatial facilitation technique was used, the effects on the Q H reflex of two conditioning stimuli (applied to the CPN and the femoral nerve - FN) being compared when applied separately and together. When the two conditioning volleys were timed to reach the spinal cord simultaneously the facilitation of the H reflex on combined stimulation was larger than the algebraic sum of the effects by separate stimuli in 40% of the cases. It is argued that this additional facilitation reflects summation at a premotoneuronal level and it is concluded that non-monosynaptic Ia excitation of Q MNs from Q and pretibial flexors is, at least partly, mediated through a common pathway. In those individual units in which stimulation of the FN and/or the CPN evoked a non-monosynaptic Ia excitation, this excitation was reduced on combined stimulation of the two nerves. It is argued that this reflects inhibition of the interneurones mediating the excitation, i.e. consists in a disfacilitation of the MNs. It is suggested that the non-monosynaptic (homonymous and heteronymous) Ia excitation of Q MNs in man (and the inhibition of this excitation) is mediated through a system of neurones similar to the system recently described in the cat by Edgley and Jankowska (1987). PMID- 2591508 TI - Motor programmes for goal-directed movements are continuously adjusted according to changes in target location. AB - We have studied fast arm movements in response to double-step stimuli in two dimensional space. In a previous paper we found that such movements did not start in the direction of the first or the second target, but in a direction between the two targets. The initial movement direction was found to depend in a continuous fashion on the inter-stimulus interval and on the reaction time. Therefore we concluded that the internal representation of a discrete target displacement is a gradually shifting internal target, moving from the first to the second target location. In this paper we investigate whether the arm movements also show a modification of the trajectory during the movement. An inter-stimulus interval of 100 ms was chosen, because then the initial movement direction is the same as in the response to a single-step displacement. We found that on average double-step trajectories deviate significantly from their original trajectory within 60 ms, and in some cases even within 30 ms of the start of the movement. We conclude that a motor programme is centrally modified according to a changed target location. We hypothesize that the generation of the motor programme starts after the target presentation, and that the activation levels for the appropriate muscles are continuously adjusted to move the hand in the direction of the current internal representation of the target. PMID- 2591507 TI - Foveal tracking cells in the superior temporal sulcus of the macaque monkey. AB - Visual responses were recorded from neurons in the superior temporal sulcus (STS) of awake, behaving cynomolgus monkeys trained to fixate a small spot of light. Visual receptive fields, directionality, and responses during visual tracking were examined quantitatively for 50 cells in the foveal portion of the middle temporal (MT) visual area and surrounding cortex. Directionality indices and preferred directions for tracked and nontracked stimuli were compared. Eighteen cells (18/50 = 36%) were found to respond preferentially during tracking (tracking cells), 7 within MT, 9 in area FST on the floor of the STS, and 2 in unidentified areas. Three distinctly different tracking response profiles (VTS, VTO, and T) were observed. VTS and VTO cells had foveal receptive fields and gave directionally selective visual responses. VTS cells (3 in foveal MT, 6 in FST, 1 in an unidentified area) had a preferred visual direction that coincided with the preferred tracking direction, and began responding 50-100 ms before the onset of tracking. VTO cells (4 in foveal MT, 0 in FST, 1 in an unidentified area) had a preferred visual direction opposite to the preferred tracking direction, and began responding 0-100 ms after the onset of tracking. T cells (0 in MT, 3 in FST) had no visual responses and began responding simultaneously with the onset of tracking. It is suggested that this region of the brain could be the primary location for converting direction-specific visual responses into signals specifying at least the direction of an intended pursuit movement. PMID- 2591509 TI - Distribution of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in the rat brain. I. Forebrain. AB - In the first of two papers dealing with the distribution of glial fibrillary acidic protein-(GFAP)-immunoreactive elements in the rat brain, the localization of immunostaining in the forebrain is systematically described. While the limbic cortex was found to contain intensely stained, evenly distributed astrocytes, the neocortex showed clearly stratified GFAP-staining, with substantially less immunoreactivity occurring in the middle layers than in the areas close to the brain surface or the white matter. A remarkably regular staining pattern was observed in the hippocampus and dentate gyrus. The striatum remained unstained in sharp contrast to the pallidum. In the diencephalon, the main thalamic nuclei were poor in GFAP-labelled elements in contrast to the internuclear border zones. In the hypothalamus, nuclei were conspicuous by their GFAP-staining. A consistent differential staining pattern was obtained in the epithalamic structures. The observed distributional pattern of diencephalic GFAP-immunoreactivity is thought to be due to different regional proliferation of the embryonic neuroepithelium of the diencephalon. The uneven distribution of GFAP-immunoreactivity in the forebrain is explained on a mainly developmental basis. PMID- 2591510 TI - Distribution of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in the rat brain. II. Mesencephalon, rhombencephalon and spinal cord. AB - The topographical mapping of glial fibrillary acidic protein (GFAP) immunoreactivity was performed in coronal serial sections of the rat mesencephalon, rhombencephalon and spinal cord. Relative to a background of poor or moderate overall staining of the mesencephalon, the interpeduncular nucleus, substantia nigra and the periaqueductal grey matter were prominent by their intense GFAP-immunoreactivity. The pons and particularly the medulla contained more GFAP-labelled elements compared with the mesencephalon. The spinal trigeminal nucleus and Rolando substance were distinguished by their intense staining. Large fibre tracts were usually poor in immunoreactive GFAP. In a concluding discussion, findings relevant to the GFAP-mapping of the whole rat CNS are evaluated with regard to possible reasons underlying the observed differential distribution of GFAP-immunoreactivity. PMID- 2591511 TI - Alterations in brain monoamine neurotransmitter release at high pressure. AB - High pressure exposure produces neurological changes which manifest as tremors, EEG changes and convulsions. Since previous studies have implicated the involvement of the monoaminergic system in these symptoms, it was of interest to study monoamine release at high pressure. Synaptosomes isolated from guinea pig brain were used to follow monoamine efflux at 68 ATA. The major observation was a decrease in the initial calcium dependent release of all three monoamines in response to K+ induced depolarization. This response is similar to that previously observed for GABA, glycine and glutamate. This generalized pressure induced depression of initial transmitter release suggests a mechanism common to the release process for both excitatory and inhibitory neurotransmission. PMID- 2591512 TI - A face-responsive potential recorded from the human scalp. AB - Evoked potentials were recorded to the separate tachistoscopic presentation of a variety of faces and other simple and complex visual stimuli. A positive potential of 150-200 ms peak latency which responds preferentially, but not exclusively, to faces was identified in 8 out of 9 subjects. This potential, best recorded from midline central and parietal electrodes, was evoked by all face stimuli, including photographs, outline drawings, and fragmentary figures. Changes in stimulus size and other parameters which do not affect the clarity of the face, generally had little effect on the peak amplitude. Stimulus changes such as face inversion, reversing the contrast polarity of photographic images, and selectively removing particular facial features, produced a marked increase in latency but often only slight attenuation of this peak. These response properties correspond well with those reported for face-related single cells in the temporal cortex of the rhesus monkey. The scalp distribution of this face responsive peak also appears consistent with bilateral sources in the temporal cortex. PMID- 2591513 TI - Effects of dark rearing on the development of visual callosal connections. AB - It is now well established that during normal postnatal development there is a partial elimination of the callosal projections of cortical areas 17 and 18 in the cat and that visual experience early in life can modulate this process. In the present experiments, we quantitatively studied the influence of light, per se, by rearing cats in total darkness. Dark rearing exaggerates the normally occurring partial elimination of immature callosal projections: it causes a significant reduction in the total number of neurons in both the supra- and infragranular layers that send an axon through the corpus callosum and slightly narrows the distribution of these neurons across areas 17 and 18. These data demonstrate that visual stimulation is not necessary either to initiate the partial elimination of immature callosal projections or to stabilize a large fraction of the callosal projections present at birth. However, normal visual stimulation is necessary for the stabilization of the normal complement of callosal projections. PMID- 2591514 TI - Facilitation of quadriceps motoneurones by group I afferents from pretibial flexors in man. 2. Changes occurring during voluntary contraction. AB - The facilitation of the quadriceps (Q) H reflex evoked by stimulation of group I afferents from pretibial flexors exhibits biphasic changes during Q voluntary contraction. At short conditioning-test intervals the facilitation is increased, whereas it is decreased at longer intervals and/or at high conditioning stimulus intensities and/or when the contraction strength is increased. The spatial facilitation at a premotoneuronal level observed at rest on combined stimulation common peroneal nerve (CPN) and femoral nerve (FN) - regularly disappeared during contraction. It is argued that the increase in facilitation at the onset of the weakest Q contraction reflects a descending facilitation of the interneurones mediating the CPN-induced excitation to Q MNs. An occlusion of descending and peripheral excitation in these interneurones can easily account for the depression of the facilitation when the conditioning stimulus intensity and/or the strength of the contraction is increased. However, occlusion cannot explain all the results and inhibition of the neurones mediating excitation of MNs, i.e. disfacilitation of the MNs, probably contributes to the decrease in facilitation observed during contraction. PMID- 2591515 TI - Methodological implications of the post activation depression of the soleus H reflex in man. AB - A long lasting inhibition (greater than 8 s) of the soleus Hoffmann reflex (H reflex) was evoked by a preceding soleus H-reflex, by a brief voluntary ankle flexor or extensor muscle contraction or by a tap applied to the Achilles tendon. The time course of this long lasting inhibition was similar in all these cases, suggesting that the same spinal mechanism is involved. Furthermore, it was shown that the post-activation depression may interfere with the determination of inhibitory or facilitatory effects on the H-reflex. It is stressed that when the onset of inhibitory or facilitatory effects on the soleus H-reflex is to be determined in relation to start of an ankle movement, either very long stimulus intervals (greater than 8 s) must be used, or the onset must be determined in relation to a reference value of the soleus H-reflex, which may be influenced by the long lasting inhibitory effect, but not yet by the succeeding muscle contraction. PMID- 2591517 TI - Monoclonal antibody VC1.1 selectively stains a population of GABAergic neurons containing the calcium-binding protein parvalbumin in the rat cerebral cortex. AB - Monoclonal antibody VC1.1 is shown to stain selectively a subpopulation of GABAergic neurons in the rat cerebral cortex. Almost all VC1.1 immunoreactive cells were also GABA-like immunoreactive (GABA-LI) and parvalbumin (PV) immunoreactive, whereas they were about 30% and 65% of GABA-LI and PV-positive cells in the parietal cortex and about 13% and 32% in the occipital cortex, respectively. Although a few VC1.1 positive cells showed somatostatin-like and/or cholecystokinin-like immunoreactivities, they were exceptional (less than 1% of VC1.1 positive cells). Furthermore about 90% of VC1.1 positive cells were also stained with a lectin, Vicia villosa agglutinin, with a specific affinity for terminal N-acetylgalactosamine. PMID- 2591516 TI - Coexistence of glucocorticoid receptor-like immunoreactivity with neuropeptides in the hypothalamic paraventricular nucleus. AB - The paraventricular nucleus (PVN) of male albino rats was analyzed for the presence of glucocorticoid receptor-like immunoreactivity (GR-LI) in neuropeptide containing neurons. Using immunohistochemistry, coronal sections trough the entire PVN were double-stained with a mouse monoclonal antibody against GR and one of the following antisera: rabbit antiserum to corticotropin releasing factor (CRF), neurotensin (NT), enkephalin (ENK), cholecystokinin (CCK), thyrotropin releasing hormone (TRH), galanin (GAL), peptide histidine isoleucine (PHI), vasoactive intestinal polypeptide (VIP), somatostatin (SOM) or tyrosine hydroxylase (TH). For comparison the occurrence of GR-LI in NT-, SOM-, NPY- or TH positive neurons of the arcuate nucleus was also studied. Our results indicate that GR-LI is present in the parvocellular part of the PVN but not in its magnocellular portion. Virtually every parvocellular neuron in the PVN containing one of the above mentioned peptides was also positive for GR, with the exception of SOM neurons, of which only about two thirds showed detectable levels of GR-LI. All TH-positive, presumably dopamine neurons in the PVN were GR-positive. In the arcuate nucleus all TH- and NPY-positive neurons as well as a large proportion of the SOM- and NT-immunoreactive neurons contained GR-LI. The results indicate that in the PVN, in addition to the CRF neurons, certain peptidergic neurons in the parvocellular part of the PVN, without any established role in the control of ACTH synthesis and release, may also be under glucocorticoid control. This seems to be the case also for most arcuate neurons. PMID- 2591518 TI - Physiological properties of the motor units of the wrist extensor muscles in man. AB - The physiological properties of 355 motor units (MUs) recorded in the extensor carpi radialis muscles were studied in 34 healthy human subjects during isometric contractions. MU selective twitches were educed from the whole muscle force using the spike-triggered averaging method. The twitch contraction times and twitch forces were measured. From these data it was attempted to estimate the distribution of fast and slow MUs in the muscles studied. Mu recruitment thresholds were systematically measured during stereotyped slow ramp contractions (force increase = 0.25 N. s-1). Degrees of correlation between contraction times, twitch forces and recruitment thresholds were pair analysed by computing simple regression curves and correlation coefficients. The degrees of correlation were compared between 245 Mus recorded in 34 subjects and 66 MUs recorded in a single subject. Analysis of the instantaneous discharge frequency of 132 MUs showed the existence of a remarkable degree of correlation (correlation coefficient, r = 0.75) between the "frequency rise times" (discharge onset to maximal frequency) and the MU twitch contraction times; i.e., the "frequency rise times" increase when the twitch contraction time decrease. The possibility that muscle contraction may be differentially modulated on the basis of this discharge property of the M Us is discussed. The results are compared to previous data and the limitations of the spike-triggered averaging method applied to long muscles in man are extensively discussed. PMID- 2591519 TI - Tactile discrimination of thickness. AB - The ability of human subjects to discriminate plane metal plates of different thickness was measured using of forced-choice paradigm. The plates, made by electroplating a thin layer of copper onto flat brass shims, were gripped between the thumb and the index finger. Subjects were presented with either 2 standard plates (0.2 mm thick), or a standard plate and a test plate that was slightly thicker, and were required in state which alternative had occurred. When the edges of the plates could not be touched, a difference in thickness of about 0.075 mm could be discriminated. Surprisingly, when the edges were included in the grip, performance did not improve. All hypotheses of strategies used by the subjects required them to sense the angles of the finger joints with a precision of about 0.1 degrees. PMID- 2591520 TI - Similarities between aberrant serotonergic fibers in the aged and 5,7-DHT denervated young adult rat brain. AB - Recent morphological observations have suggested neurotransmitter specific degeneration of amongst others, the serotonergic system in the aged rat brain. However, morphological studies can only give a static picture of the events that take place over a period of several months. In the present study we used an experimental model in which degeneration of the serotonergic system in the young adult rat brain was produced on a short time scale. Morphological changes were studied 2 h and 1 or 14 days after intracerebroventricular injection of 5,7 dihydroxytryptamine (5,7-DHT). Non-specific damage and severe depletion of serotonergic fibers was observed in the immediate surroundings of the injection site, representing the effects of high local concentrations of 5,7-DHT. Sometime after injection swollen varicosities and dilated non-varicose fibers were observed. Fourteen days after the 5,7-DHT treatment cluster-like fibers appeared. It is argued that these swollen and crumpled fiber knots are slowly degenerating fibers. A comparison is made with the abnormal serotonergic fibers in the aged rat brain and it is concluded that these aged abnormal fibers represent axonal degeneration of the serotonergic system in the senescent rat brain. PMID- 2591521 TI - Representation of the fovea in the superior temporal sulcus of the macaque monkey. AB - The response properties of 633 neurons from striate and prestriate cortex were recorded in 3 hemispheres of two awake cynomolgus monkeys while they fixated or tracked a small spot of light. Of 254 penetrations located at 1 mm intervals, 39% were identifiable from visible electrolytic lesions or electrode tracks and were used to reconstruct the positions of all recording sites. A total of 226 cells were located in the superior temporal sulcus and 81 cells in area V1. The location and visuotopic organization of the foveal portion of the middle temporal (MT) visual area were determined in three hemispheres. MT was defined physiologically on the basis of direction-selectivity, receptive field size, and retinotopic organization. Of 170 MT neurons, most were motion sensitive, and 65% had a directionality index, (best-opposite)/best, of 0.6 or higher. MT was defined anatomically on the basis of myelin staining within the superior temporal sulcus (STS). On the posterior bank of the STS the physiologically defined border corresponded closely to a myelin border visible on our sections. Distinct myelin borders were not consistently identifiable on the anterior bank. The representation of the central fovea (eccentricities of 0-1 deg) was located partly on the floor, but mostly on the posterior bank of the STS at the extreme postero-lateral edge of MT. In all three hemispheres foveal MT extended onto the roof of a cleft formed between the posterior bank and a wide flattened area on the floor of the STS. This region lies 10-12 mm below the brain surface, measuring along a line normal to the surface at a point 2-3 mm antero-lateral to foveal V1. The area of MT was 6-9 mm2 for the central fovea (0-1 deg), 15-24 mm2 for the entire fovea (0-3 deg), and 28-40 mm2 including the fovea and parafovea (0-10 deg). A visuotopic map of central foveal V1 (0-1 deg) was obtained in one animal. The measured area of this representation was 116 mm2. Using published estimates of the total areas of cynomolgus MT and V1 (73 and 1200 mm2 respectively) the ratio of central foveal to total area was calculated to be 0.10 for both MT (7.5/73) and V1 (116/1200), indicating that the relative magnification of the foveal versus the peripheral visual field is preserved in the mapping of V1 onto MT. A separate representation of the central visual field was found immediately adjacent to foveal MT.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2591522 TI - The amyloid precursor protein is concentrated in neuronal lysosomes in normal and Alzheimer disease subjects. AB - The 4.2-kilodalton (kDa) polypeptide associated with the cerebral amyloid deposits of Alzheimer's disease (AD) derives from a much larger protein that is encoded by a gene on chromosome 21. In the present study, we have used antibodies raised against portions of the amyloid protein precursor (APP) to map its normal distribution and to gain further insights into the events that lead to amyloid deposition. Antibodies raised against several different portions of APP reacted with proteins having apparent molecular sizes of 65, 67, and 132 kDa on Western blots. In sections through the normal human brain, immunocytochemistry revealed punctate concentrations of the protein in pyramidal cells of the neocortex, particularly in associative regions, and intense staining in the CA1 pyramidal cells of the hippocampus. By electron microscopy, this punctate distribution coincided with dense concentrations of the protein in secondary lysosomes. In the hippocampus of several AD cases examined, abnormally dense immunostaining in enlarged intracellular domains accompanied a severe atrophy of the CA1 neurons. These data suggest that accumulations of APP in lysosomes of particular neurons may, in AD, lead to proteolytic events that form the insoluble 4.2-kDa amyloid peptide. PMID- 2591524 TI - The effect of L-dopa upon in vitro dopamine release from the corpus striatum of young and old male rats. AB - In the present experiments, we examined the effects of superfusion of L-DOPA upon in vitro dopamine (DA) release from the corpus striatum (CS) in young (2-4 months) and old (24 months) male rats. In Experiment I, responses to two successive increasing doses of L-DOPA (1.0 and 10 microM) indicated a clear age difference with DA release from CS of young rats significantly greater than that of old rats in response to the 10 microM dose of L-DOPA. Interestingly, CS fragments of young and old male rats responded marginally to the 1.0 microM L DOPA infusion, and no significant differences between these two age groups were obtained. Since we have previously observed that the addition of naloxone to the superfusion medium restored the potassium stimulated DA release of old rats to that of young rats, in Experiment II, responses of CS tissue fragments of young and old rats superfused in medium with or without naloxone (100 microM) were tested with a single 10 microM L-DOPA infusion. The results of Experiment II indicated that the addition of naloxone to the superfusion medium did not alter the responses of CS tissue to L-DOPA in either young or old rats; however, the overall response of the young rats remained significantly greater than that of the old rats. Taken together, these results demonstrate a significant age-related decrement in the capacity of 10 microM L-DOPA to stimulate DA release from CS fragments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591523 TI - Visualizing manganese in the primate basal ganglia with magnetic resonance imaging. AB - The paramagnetism of manganese was exploited to obtain proton nuclear magnetic resonance (MR) images of manganese-rich tissue in the central nervous system in vivo. One Macaca fascicularis monkey inhaled MnCl2 aerosol prior to imaging. A second M. fascicularis and two Cebus apellas were administered MnCl2 in various doses intravenously. The monkeys' brains were imaged before and after manganese administration in coronal and horizontal planes that included the basal ganglia and substantia nigra. A T1-weighted pulse sequence exploited manganese's reduction of spin-lattice relaxation times and clearly distinguished several separate and specific regions after manganese administration: the caudate nucleus, the lenticular nuclei, the substantia nigra, a region corresponding to subthalamic nucleus and ventromedial hypothalamus, and the pituitary gland. The kinetics of manganese accumulation were important in determining the imaged intensity of these regions but the route of parenteral administration was not. Spin-lattice relaxation times showed that T1 was shortened at lower doses of manganese and remained shortened longer in the globus pallidus and pituitary gland while little effect appeared in gray and white matter. T1 effects in caudate and putamen effects were intermediate. These data suggest selective affinity for manganese in globus pallidus and pituitary. PMID- 2591525 TI - Morphometric analysis of developing rat cerebral cortex following acute prenatal ethanol exposure. AB - Morphologic alterations of fetal rat cerebral cortex were quantified by morphometric analysis following acute ethanol exposure on Gestational Day 14, a critical period of development of cerebral cortex. Pregnant rats were intubated with a total dose of 9 g/kg of ethanol on Gestational Day 14. Maternal blood ethanol levels ranged from 51 to 202 mg% during the period of ethanol exposure. Fetal brains were examined on Gestational Day 15, 24 h after the last dose of ethanol. The acute morphologic changes associated with ethanol exposure include enlargement of subventricular zone nuclei, cortical swelling, and dilation of pial blood vessels over the affected cortex. In some fetuses, cortical swelling was accompanied by the protrusion into the lateral ventricles of cytoplasmic blebs of ventricular zone cells. It is concluded that maternal ethanol exposure during a critical period of brain development produces measurable morphologic changes in fetal rat cerebral cortex within 24 h after ethanol exposure. PMID- 2591526 TI - Surface enhanced resonance Raman scattering (SERRS) as a probe of the structural differences between the Pr and Pfr forms of phytochrome. AB - Surface enhanced resonance Raman scattering (SERRS) spectra have been obtained from the active, far-red light absorbing (Pfr) and biologically inactive (Pr) forms of phytochrome adsorbed on silver colloids. Substantial differences between the SERRS spectra of the two forms in the low and high wavenumber regions are observed using 406.7 nm wavelength excitation. These differences reinforce those seen with 413.1 nm wavelength excitation in the high wavenumber region. Simultaneously, extensive differences are observed in the SERRS obtained from the same form in the low wavenumber region using 406.7 nm, as compared with 413.1 nm wavelength excitation. The relative intensity differences observed for the two forms, and those obtained using two slightly different excitation wavelengths to illuminate the same form, suggest that some type of subtle, protein-controlled structural variation is responsible for the spectroscopic differences. AZ----E isomerization during the Pr----Pfr phototransformation is consistent with the SERRS data, although the overall chromophore conformations are most likely conserved for the native Pr- and Pfr-phytochrome species. Slight out-of-plane ring twisting, accompanying the Pr----Pfr photoisomerization, may be responsible for the large difference in the spectroscopic properties of the native Pr and Pfr chromophores. PMID- 2591527 TI - Phosphorylation of P1, a high mobility group-like protein, catalyzed by casein kinase II, protein kinase C, cyclic AMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II. AB - P1, a high mobility group-like nuclear protein, phosphorylated by casein kinase II on multiple sites in situ, has been found to be phosphorylated in vitro by protein kinase C, cyclic AMP-dependent protein kinase and calcium/calmodulin dependent protein kinase II on multiple and mostly distinct thermolytic peptides. All these enzymes phosphorylated predominantly serine residues, with casein kinase II and protein kinase C also labeling threonine residues. Both casein kinase II and second messenger-regulated protein kinases, particularly protein kinase C, might therefore be involved in the physiological regulation of multisite phosphorylation of P1. PMID- 2591528 TI - Papaya proteinase IV amino acid sequence. AB - The amino acid sequence of papaya proteinase IV (PPIV), a major proteinase from the latex of Carica papaya [(1989) Biochem. J. 261, 469-476] is described. The enzyme has a high degree of sequence identity with papaya proteinase III, chymopapain and papain (81, 70 and 67%, respectively), and is clearly a member of the papain superfamily of cysteine proteinases. Nevertheless, the sequence shows substitution of certain residues conserved in all other known members of the superfamily. It is suggested that some of these substitutions may account for the unusual specificity of PPIV. PMID- 2591529 TI - Multiple charge isomers of human recombinant interleukin-1 beta. AB - Human interleukin-1 beta (rhuIL-1 beta), obtained by DNA recombinant technology, was radiolabelled. Its isoelectric properties were determined by various analytical techniques such as high-voltage ultrathin layer isoelectric focusing (IEF) and chromatofocusing. The rhuIL-1 beta molecule had a molecular mass of 18 kDa, as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. When examined by IEF on a polyacrylamide gel of 1 mm thickness in the pH range of 3.5-9.5, it was resolved into two broad bands appearing in the pH range of 6.2 5.8 and 5.5-5.2. Each of the two bands was further resolved into multiple bands when electrofocused on (i) a thinner gel of 0.5 mm thickness and (ii) a narrower pH range of 5-8. Upon chromatofocusing in a liquid column, it was possible to isolate various charged components of rhuIL-1 beta. However, all these components reacted to the antiserum to rhuIL-1 beta and displayed a molecular mass of 18 kDa suggesting the charge heterogeneity of rhuIL-1 beta. PMID- 2591530 TI - Effect of adenosine on fructose 2,6-bisphosphate levels and glucose metabolization by chicken erythrocytes. AB - Adenosine can be metabolized by chicken erythrocytes as a carbon source maintaining ATP levels. In addition, it stimulates glucose uptake and lactate production. Adenosine effects do not involve binding to membrane receptors. They are dependent on the provision of a carbon source to glycolysis and correlate with the increase of fructose 2,6-bisphosphate levels that activating phosphofructokinase would increase the glycolytic flux. PMID- 2591531 TI - Suramin, an anti-cancer drug, inhibits protein kinase C and induces differentiation in neuroblastoma cell clone NB2A. AB - Protein kinase C purified from rat brain was found to be inhibited by suramin, a substance used originally in the therapy of antitrypanosomic infections and more recently proposed as antineoplastic agent. The inhibition of suramin was competitive with one of the substrates of the enzyme, ATP with a Ki of 10 microM. At concentrations adequate to inhibit the isolated enzyme, suramin was shown to slow the rate of proliferation of neuroblastoma NB2A cells in vitro and to induce their differentiation as evidenced by typical morphological changes. PMID- 2591532 TI - Lambda plac10 transducing bacteriophage: DNA primary structure of the region of the abnormal excision. AB - In studying molecular mechanisms of the formation of transducing bacteriophages, we have elucidated the primary structure of the phage-bacterial DNA junction which resulted from the abnormal excision of the lambda plac10 phage. The process is structurally similar to the excision of the lambda plac5 phage and involves, in both cases, highly homological DNA stretches approximately 20 bp long, one of them being a part of the Z-Y spacer of the lac operon and possessing a developed secondary structure. The conception of regioselective recombination as a type of illegitimate recombinational process with a certain degree of site-specificity is suggested. PMID- 2591533 TI - Animal and plant mitochondria contain specific thioredoxins. AB - Thioredoxins have been purified from pig heart and potato tuber mitochondria which differ in chromatographic behaviour, enzyme activating capacity, and slightly higher molecular mass (Mr = 12,500) from the major thioredoxin(s) present in mitochondria-free fractions of the same tissue. Both mt-thioredoxins can serve as hydrogen donor for E. coli ribonucleotide reductase but only the plant protein activates spinach chloroplast NADP malate dehydrogenase in vitro. Mitochondrial target enzymes specifically activated by thioredoxin have not as yet been identified. PMID- 2591534 TI - Metabolism of peripheral lymphocytes, interleukin-2-activated lymphocytes and tumor-infiltrating lymphocytes from 31P NMR studies. AB - 31P NMR spectra of tumor-infiltrating lymphocytes (TILs) were found to be significantly different from those of normal peripheral lymphocytes. The greatest difference was in the phosphodiester (PDE) region, mainly in the glycerophosphocholine (GPC) signal. Short-term activation of peripheral lymphocytes with interleukin-2 induced a small increase in ATP levels. In all lymphocytes the phosphomonoester (PME) region is dominated by phosphoethanolamine (PE), while there is an unusual absence of phosphocholine (PC). Perfusion of these cells with high concentrations of choline caused only a minimal increase in PC, indicating that choline kinase is not the rate limiting step of lecithin synthesis in lymphocytes. PMID- 2591535 TI - Rapid myosin phosphorylation transients in phasic contractions in chicken gizzard smooth muscle. AB - In intact smooth muscle strips from chicken gizzard, electrical stimulation and carbachol elicited brief, phasic contractions which were associated with a very rapid, transient phosphorylation of the 20 kDa myosin light chains. The phosphorylation transients reached their peak after 3 s and 6 s and preceded that of force. Phosphorylation was not significantly different from basal levels after 10 s and 30 s while force still amounted to 50% of the peak value. The rate of tension decline could be increased by cessation of stimulation or by addition of atropine, even at apparently basal phosphorylation levels suggesting a phosphorylation independent regulation. PMID- 2591536 TI - Direct sequencing of affinity-captured amplified human DNA application to the detection of apolipoprotein E polymorphism. AB - We describe a method for the direct sequencing of DNA amplified by the polymerase chain reaction (PCR). Biotin is introduced into one strand of the amplified DNA using a 5'-biotinylated PCR primer. The synthesized fragment is captured on an avidin-matrix and rendered single stranded, whereafter the nucleotide sequence of the immobilized strand is determined by the chain termination method. The method involves few and simple operations and is thus applicable to the analysis of human genes for routine diagnostic purposes. Here we applied the method for determination of the three-allelic polymorphism of the apolipoprotein E (apo E) gene. We were able to correctly identify the alleles in both homozygous and heterozygous samples. PMID- 2591537 TI - Molecular cloning and characterization of the complementary DNA coding for the B chain of murine Clq. AB - cDNA clones coding for the B-chain of murine Clq were isolated from a mouse macrophage library. The characterized clones include the total coding region plus a leader sequence. High homology was found with human Clq B-chain in the coding region (81%). Northern blot analysis of total RNA from different tissues of Balb/c mice showed one band of approximately 1.2 kb. The highest signal was found in RNA preparations of thioglycolate-activated peritoneal macrophages. The probe also hybridized with mRNA from spleen, thymus and heart. Extremely weak signals were found in liver, kidney, lung and intestine tissues. PMID- 2591538 TI - Regulation of glutathione S-transferase subunits 3 and 4 in cultured rat hepatocytes. AB - mRNA levels of glutathione S-transferase (GST) subunits 3 and 4 were measured with a specific cDNA probe in adult rat hepatocytes maintained either in conventional culture or in coculture with rat liver epithelial cells. Four media conditions were used, i.e. with or without fetal calf serum (FCS) and with nicotinamide or dimethylsulfoxide (DMSO). When FCS was present in the culture medium, GST subunit 3 and 4 mRNAs were expressed at a level close to that found in freshly isolated hepatocytes during the whole culture period both in conventional culture and in coculture. All other culture conditions resulted in an increase of GST 3 and 4 mRNA levels. After exposure to phenobarbital an increase in GST 3 and 4 mRNA levels was demonstrated in both culture systems. Comparison with previous findings on the expression of GST subunits 1, 2 and 7 in the same culture conditions indicates that the different classes of GST are regulated independently. PMID- 2591539 TI - [Dacryocystitis in newborn infants]. PMID- 2591540 TI - [The adaptation reactions of children and their significance in clinical practice]. PMID- 2591542 TI - [Periodontitis]. PMID- 2591541 TI - [The treatment of hand injuries and diseases in children]. PMID- 2591543 TI - [Radiation reactions in the radiology clinic]. PMID- 2591544 TI - [Electric trauma]. PMID- 2591545 TI - [Determination of the thoroughness of the examination of the population in the preventive medicine departments of outpatient polyclinic institutions]. PMID- 2591546 TI - [The use of calcium antagonists for treating hypertension]. PMID- 2591547 TI - [The use of the products of bee raising in medicine]. PMID- 2591548 TI - [Olympiads in clinical disciplines in the medical school]. PMID- 2591549 TI - [Nondeveloping pregnancy]. PMID- 2591551 TI - [Pernicious anemic coma]. PMID- 2591550 TI - [The hygiene of computer instruction in school]. PMID- 2591552 TI - [Cancer of the ovaries]. PMID- 2591553 TI - [Physical exercise in the prevention of spinal osteochondrosis at the N. N. Priorov Cental Research Institute of Traumatology and Orthopedics of the Ministry of Public Health, Moscow]. PMID- 2591554 TI - [Recommendations for using medical physical exercise in patients with cerebral circulatory disorders]. PMID- 2591555 TI - [The role of homosexuality in the spread of sexually transmitted diseases]. PMID- 2591556 TI - [Congenital hypotrophy, the prenatal risk factors for fetal developmental retardation]. PMID- 2591557 TI - Correlation between follicular fluid content and the results of in vitro fertilization and embryo transfer. I. Sex steroids. AB - The steroid content of 72 follicular fluids (FF) obtained from 42 women subjected to ovulation induction with the luteinizing hormone-releasing hormone analogue D Trp6 and human menopausal gonadotropin was studied in terms of the evolution of in vitro fertilization (IVF) and embryo transfer (ET) results. The FF were classified into several categories based on oocyte evolution. Individual values of FF estrone and estradiol (E2), as well as androstenedione and testosterone could not be correlated with ET outcome. However, FF progesterone (P) levels for follicles leading to pregnancy were significantly lower when compared with those in the other categories. The correlation between the E2/P ratio and E2 permitted the definition of a band wherein IVF-ET outcome was successful and enabled the characterization of different functional follicular maturational states. PMID- 2591558 TI - Gamete intrafallopian transfer: benefits of programmed stimulation. AB - Fifty-six cycles of gamete intrafallopian transfer (GIFT) were performed after programming by administration of norethisterone in the previous cycle. Ovarian hyperstimulation was achieved with clomifene citrate and human menopausal gonadotropins. Only one GIFT was performed during a weekend (1.8%). The implantation rate was 41.1% and the evolutive pregnancy rate 30.4%. The endocrinological influence of these regimens are discussed by comparison of those observed in an in vitro fertilization program. The main influence is a decreased serum luteinizing hormone (LH) level in the preovulatory phase. PMID- 2591559 TI - Low incidence of sperm antibodies in men with congenital absence of the vas deferens. AB - The incidence of antisperm antibodies in serum and seminal fluid of 27 azoospermic men with congenital absence of the vas deferens is evaluated. The presence of antisperm antibodies was assessed using the immunobead test, the agglutination test, and immobilization test. Five patients with vasovasostomy or vasoepididymostomy attempts were included in the study and tested for the presence of antisperm antibodies. Contrary to a previous report, a low incidence (11%) of antisperm antibodies has been found in patients with congenital absence of the vas. In agreement with previous studies, in five patients who had failed vasoepididymostomy or vasovasostomy, a high incidence (71%) of antisperm antibodies was found. PMID- 2591560 TI - Effect of different procedures of semen preparation on antibody-coated spermatozoa and immunological infertility. AB - To assess whether procedures of semen preparation can reduce the proportion of antibody-coated spermatozoa, semen samples with positive direct mixed antiglobulin reaction (MAR) were washed in media supplemented with 10% or 50% fetal cord serum (FCS). Washing reduced the MAR to a negative level, but the MAR was identical to that in the native semen when spermatozoa were resuspended in serum-free medium. Donor spermatozoa, recovered after swim-up in media supplemented with 10% or 50% FCS or after passage through a column with 7.5% human serum albumin (HSA), were incubated in serum samples with both agglutinating and cytotoxic antisperm antibodies. Cytotoxic activity was significantly reduced against sperm filtered over the albumin column. PMID- 2591561 TI - Clinical significance of crossed in vitro sperm-cervical mucus penetration test in infertility investigation. AB - To evaluate the clinical significance of in vivo and in vitro testing of sperm ability to penetrate cervical mucus (CM), postcoital testing (PCT) and in vitro sperm-cervical mucus penetration testing were compared in a prospective study. Both in vivo and in vitro tests were standardized and performed after an oral course of estrogen therapy. Crossed in vitro sperm-cervical mucus penetration test, evaluated in 277 couples with CM of patients' wives and additionally with CM and semen of fertile donors, revealed that the male factor contributed to a significantly higher extent to deficient sperm-mucus interaction than the cervical factor. The overall pregnancy rate after 6 months was 23% (64/277). Whereas the outcome of PCT did not significantly predict subsequent fertility (PCT good pregnancy rate 24%/PCT poor 20%), significant differences were found for the sperm-cervical mucus penetration test with CM of patients' wives (pregnancy rate, 30.5% versus 8.5%) and for in vitro testing with donors' CM, but not for the mucus penetration test with donors' spermatozoa. Routine sperm analysis did not prove to be of prognostic value for a subsequent pregnancy. The results suggest that the in vitro sperm-cervical mucus penetration test is a good parameter of sperm function and, in particular, when performed as a cross matching penetrability test, a valuable adjunct to PCT with regard to fertility prognosis. PMID- 2591562 TI - Follicular fluid-induced acrosome reaction distinguishes a subgroup of men with unexplained infertility not identified by semen analysis. AB - We compared the ability of sperm to undergo follicular fluid-induced acrosome reaction in vitro in fertile men and patients with unexplained infertility. After capacitation under optimum conditions, 28% of sperm from fertile men undergo acrosome reaction after follicular fluid exposure, whereas only 7% of the cells react spontaneously. In 15 men with unexplained infertility, 6 patients showed lack of acrosome reaction, whereas 9 men had sperm acrosome reactions similar to that of fertile men. However, in this cohort under study, semen characteristics of AR(+) and AR(-) patients were similar. In addition to inducing sperm acrosome reaction, follicular fluid also promoted significant changes in motion characteristics of capacitated sperm. Sperm curvilinear velocity (Vc) increased significantly after exposure to follicular fluid though linearity remained unchanged. The largest difference in cumulative Vc occurred at 90 microns/s. Assessing the ability of capacitated sperm to acrosome react may have clinical significance in predicting whether such sperm are capable of fertilizing an ovum. PMID- 2591563 TI - Noncompetitive antiestrogenic effect of RU 486 in blocking the estrogen stimulated luteinizing hormone surge and the proliferative action of estradiol on endometrium in castrate monkeys. AB - The noncompetitive antiestrogenic effects of RU 486 were examined using estradiol (E2)-treated ovariectomized monkeys given RU 486, progesterone (P), or both. The E2-induced luteinizing-hormone (LH) surge of control animals was abrogated by P and/or RU 486. Secretory transformation by P was inhibited by RU 486 coadministration. RU 486 alone (1 mg/kg) induced endometrial secretory transformation, but higher doses (5 mg/kg) inhibited proliferation and secretory activity. Thus in the presence of P, RU 486 is antagonistic but, in absence of P, exhibits endometrial progestational effects at low doses and an antiproliferative (antiestrogenic) effect at higher doses. These data encourage continued evaluation of RU 486 as a potential contraceptive agent acting at the pituitary and/or endometrial level. PMID- 2591564 TI - Cardiolipin antibody levels in endometriosis and systemic lupus erythematosus. AB - Cardiolipin antibody levels were found to be significantly higher in women with endometriosis and SLE when compared with healthy women. PMID- 2591565 TI - Tetraploidy and aneuploidy after observation of diploid fertilization in vitro. AB - A case is described in which a tetraploid and aneuploid conceptus resulted from dipronuclear embryos from in vitro fertilization. This finding strongly suggests that, after a meiotic error in either the egg or sperm, polyploidy has occurred as the result of a postfertilization mitotic error. PMID- 2591566 TI - Simultaneous establishment of pregnancies in two ovarian failure patients using one oocyte donor. AB - We successfully synchronized two functionally agonadal women with a single oocyte donor who underwent controlled ovarian hyperstimulation and transvaginal aspiration. Pregnancies were simultaneously established in these recipients; the need for freezing supernumerary preembryos was obviated, and substantial cost reduction was realized by the patients. PMID- 2591567 TI - Human sperm capacitation in gelatin-fortified medium. AB - Gelatin was shown to be an effective substitute for serum albumin in human sperm capacitation. No protein-dependent differences were seen with regard to long-term retention of sperm motility, including hyperactivation, in acrosomal status or in the acquisition of fertility potential. Gelatin may serve as a cost-effective substitute for serum albumin, which carries minimal risk of infectious disease transmission. PMID- 2591568 TI - Treatment of human spermatozoa with an egg yolk medium can enhance the outcome of in vitro fertilization. AB - In at least 4 of 7 cases, fertilization of intact human oocytes was more successful when spermatozoa were pretreated with TEST yolk medium at 5 degrees C for 2 hours as compared with the standard treatment with Ham's F-10 only. Both pregnancies that were obtained after the transfer of the fertilized oocytes resulted from oocytes fertilized by TEST yolk-treated spermatozoa. No decrease in fertilization occurred in any of the cases after TEST yolk treatment. If these results hold true for a larger series of patients, it may be worthwhile for the standard IVF incubation system of spermatozoa to include TEST yolk. PMID- 2591569 TI - Assisted reproductive technology with donor gametes: the need for patient preparation. AB - There are certainly no definitive answers to the questions raised by the use of donor gametes in reproduction, as there are no definitive answers to any of life's most difficult questions. The loss of fertility is usually an unexpected, invisible, deeply painful wound for those couples who are considering the use of donor gametes. As they address the psychological issues of these techniques, they must also heal the wounds created by infertility. This type of grieving and examination of feelings takes time and information. The medical community needs to encourage each couple to resolve the issues around infertility and to use available personal, professional, and written resources to address the dilemmas raised by the use of donor gametes prior to embarking on this type of treatment. In so doing, the couple will reduce the likelihood that the means of conceiving their children will become a source of major conflict in their family. In 1932 Aldous Huxley prophesied the destructive consequences of scientific accomplishment without social involvement and psychological guidance. He said: "The sciences of matter can be applied in such a way that they will destroy life or make the living of it impossibly complex and uncomfortable...unless used as instruments by biologists and psychologists." It is our concern that the procedures for enabling infertile couples to become parents may, if not accompanied by acknowledgment of the unique challenges which they create for all participants in the process, make the living of life "impossibly complex and uncomfortable" for the very families we are trying to help. PMID- 2591570 TI - Luteal phase deficiency after completely normal follicular and periovulatory phases. AB - Luteal phase defect (LPD) accounts for a significant proportion of reproductive disorders, however its etiology is still debated. A prospective study was performed on 37 ovulatory women to determine whether LPD can occur in cycles characterized by completely normal folliculogenesis. Criteria for normal folliculogenesis included: a gradual rise of serum estradiol, a luteinizing hormone (LH) surge, the presence of a dominant follicle that disappeared, an increase of serum progesterone, and normal serum levels of prolactin, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and LH. Thirty of 37 women fulfilled the above mentioned strict criteria and underwent endometrial biopsy in the late luteal phase. Seven of 30 (23%) demonstrated a delay in endometrial development and all had normal hormonal and ultrasonographic parameters of folliculogenesis and ovulation. Women with delayed endometrial development demonstrated slightly longer follicular phases (17.0 +/- 1.1 versus 14.5 +/- 0.3 days). Perfectly normal follicular and periovulatory events may be followed by deficient luteal phases. PMID- 2591571 TI - Long-term treatment with a new repeatable injectable form of bromocriptine, Parlodel LAR, in patients with tumorous hyperprolactinemia. AB - A new long-acting repeatable injectable form of bromocriptine, (Parlodel LAR, Sandoz, Basle, Switzerland) has recently been developed. We studied the clinical, hormonal and radiological changes in six female patients with microprolactinomas and eight (3 female and 5 male) with macroprolactinomas receiving monthly injections of Parlodel LAR 50 to 100 mg for 6 months. Five patients with microadenomas and 4 with macroadenomas had normal prolactin (PRL) levels with Parlodel LAR 50 mg after one (5 patients), two (2 patients), or five (2 patients) injections; two patients with macroadenomas had normal or near normal PRL levels only after 4 monthly injections of 100 mg. Clinical improvement paralleled the changes in serum PRL. A complete normalization of a visual field defect occurred in one patient after 5 months of therapy. Marked shrinkage of the adenoma was shown by magnetic resonance and/or computed tomographical imaging in three patients with macroadenomas after 1 week. Side-effects were mild and usually transient. Parlodel LAR represents a novel treatment of hyperprolactinemic states which is both effective and well tolerated, and appears to be a useful alternative to oral therapy for long-term treatment. PMID- 2591572 TI - The effect of a specific emotional stressor on prolactin, cortisol, and testosterone concentrations in women varies with their trait anxiety. AB - The psychological and the hormonal response to a specific emotional stressor (a video film on treatment of infertility, pregnancy, and delivery) was investigated in 30 women and the responses were correlated with their trait anxiety level. The experiment included a resting period before and after the stressor. The psychological response, i.e., the change in state anxiety, was in phase with the stressor and varied with the trait anxiety level. The endocrinological response, i.e., the time courses of prolactin, cortisol, and testosterone, was not in phase but varied with the trait anxiety level. It is suggested that psychological phenomena as anticipation, mental assimilation, and reflection could explain these findings, and that these should be taken into account when investigating the so-called "psychological" infertility. PMID- 2591573 TI - Failure to demonstrate significant antisperm antibodies in peritoneal fluid of patients with endometriosis. AB - Endometriosis, even in mild cases, decreases monthly fecundity. Immunologic disorders have been suggested as the mechanism. In light of possible increases in serum autoimmune antibodies, increased peritoneal macrophages, and increased sperm phagocytosis associated with this disease, we postulated that peritoneal fluid antisperm antibodies would be increased and might be the cause of increased sperm phagocytosis and its associated infertility. Peritoneal fluid, from 18 patients with endometriosis and 10 infertile controls, was tested with the antisperm antibody immunobead test validated for peritoneal fluid. One of 18 patients with endometriosis and none of 10 controls had antisperm antibodies present. Therefore, increased sperm phagocytosis is unlikely a result of peritoneal antisperm antibodies in endometriosis patients. PMID- 2591574 TI - Contraceptive efficacy of norethindrone encapsulated in injectable biodegradable poly-dl-lactide-co-glycolide microspheres: phase II clinical study. AB - Contraceptive efficacy of injectable norethindrone (NET) microspheres of 90 day duration was evaluated for 6 months: nine women received two injections of 65 mg each and eight received two injections of 100 mg each with 90 days between each injection. Average serum NET levels were 5 to 9 ng/mL on the day after injection and subsequently remained at 1 to 3 ng/mL. With 65 and 100 mg doses, respectively, 36% and 25% of cycles had normal bleeding patterns, 36% and 48% were amenorrheic, and the remaining 28% and 27% had prolonged bleeding. Also, 56% and 40% of cycles showed increased spotting for the 65 mg and 100 mg dose, respectively. There was no incidence of pregnancy or serious side effects. The mean serum NET concentration returned to RIA nonspecific basal levels 100 days after the second injection. Women returned to ovulatory cycles between days 100 to 115 after the second injection. PMID- 2591575 TI - Clinical status of human embryo cryopreservation in the United States of America. AB - This report describes the results with frozen human embryos from 25 member institutions of the Society of Assisted Reproductive Technology with cryopreservation experience before 1989. Two thousand eighty-five patients had a total of 7397 oocytes and pre-implantation embryos frozen. The number of oocytes, zygotes, cleaved embryos, and blastocysts frozen, thawed, transferred, and the resulting number of pregnancies were 463/127/8/0, 2,133/778/540/47, 4,460/1,567/1,089/68, and 341/186/138/3, respectively. The number of embryos transferred per pregnancy and pregnancy rate per transfer for zygotes, cleaved embryos, and blastocysts were 11.5/17.4%, 16.0/12.5%, and 46.0/4.3%, respectively. The average number of frozen-thawed embryos transferred per pregnancy was 15.0 and the average clinical pregnancy rate per transfer was 13.4%. Forty-eight births have resulted in 41 singletons and 7 sets of twins. Of centers reporting frozen-thawed transfers, 54.6% (12/22) have at least one clinical pregnancy and 75.0% (9/12) of centers reporting a pregnancy have at least one birth. PMID- 2591576 TI - Delayed fertilization during in vitro fertilization and embryo transfer cycles: analysis of causes and impact on overall results. AB - This study evaluated possible causes of delayed fertilization during in vitro fertilization (IVF) cycles, its repetitiveness, and its influence on IVF results in 23 patients (27 cycles) with delayed fertilization of greater than or equal to 1 preovulatory oocyte(s). In 15 cycles, reinsemination with husband's semen was performed at 18 hours. Possible causes of delayed fertilization were oocyte defects (10 cycles, 37.0%), sperm defects (4 cycles, 14.8%), oocyte and sperm defects (4 cycles, 14.8%), and no detectable gamete defects (9 cycles, 33.3%). Overall fertilization rate was 47.9%. No pregnancies were observed in 10 patients with one embryo transferred. Recurrence rate of delayed fertilization per patient was 17.3%; overall ongoing pregnancy rate/cycle was 10.3%. Although repetitiveness of delayed fertilization is low, it seems to impact negatively on IVF results. PMID- 2591577 TI - [Pathogenetic significance of lipid peroxidation in damage of the proximal segment of the nephron in acute Masugi's nephritis]. AB - During the acute experimental nephritis a decrease of reabsorption by proximal tubules is combined with the activation of the lipid peroxidation into the renal cortex without changes in the activation of lysosomal enzyme of acid phosphatase and cathepsin D. Ionol, an inhibitor of oxygen products, exerts a protective action on the renal function and reabsorption by proximal tubules, decreasing concentration of the malondialdehyde into the renal cortex. PMID- 2591578 TI - [Changes in the pool and spectrum of adenine nucleotides in the cortex of the solitary kidney in chronic denervation]. AB - Chronic energy-++-deficient condition of nephron cortical portions manifested in a two ware pool decrease and spectrum impairment of the adenyl system components was revealed as a result of the long-term studies in tissue contents of ATP, ADP, AMP in the rat renal cortex under conditions of experimental combination of compensatory hypertrophy and chronic nervous decentralization. A negative trophic effect of chronically overloaded cortex tissue de-mediation is responsible for energy metabolism at the early phase while at the later stage, beginning two months after the experiment, the progressing hypoperfusion of the cortical tubular system of a single denervated kidney is. PMID- 2591579 TI - [Heat production as a criterion of adrenergic regulation of metabolic processes of the myocardium]. AB - Bolus injection of adrenaline in coronary perfusion blood flow caused different directed changes in coronary venous blood temperature. Directivity and myocardium heat production changes are determined by peculiarities of interactions between adrenergic and cholinergic mechanisms of cardiodynamics and myocardial metabolism regulation. Cholinergic blockade by atropine++ increases heat production and limits negative ino- and chronotropic components of cardiac adrenergic reactions. That increase is completely eliminated by subsequent obsidan blockade of beta adrenoreceptors. PMID- 2591580 TI - [Characteristics of the composition of fluorescent lipopigments of the liver and brain in rats of various ages]. AB - Spectral characteristics of the lipid liver and brain extracts were studied in experiments on rats of different age (1, 3, 12, 24 months). The aim of the experiments was to study age peculiarities of the lipopigments composition by means of thin-layer and liquid chromatography. Different fractions of lipids which differ in spectral absorption and fluorescence were extracted. Proceeding from the results obtained certain conclusions may be derived: the processes of structural recombination of the whole lipid constituents are accompanied by the age accumulation of lipofuscin; the process of accumulation of lipofuscin is not monotonous and has pronounced age peculiarities; the formation of the lipid pigment complex is tissue-specific. PMID- 2591581 TI - [Relation of atherogenesis and T-immunodeficiency]. AB - Experiments on rabbits have shown that state of T-immunodeficiency induced by persisting virus infection promotes atherogenesis. Correction of age immunodeficiency by transplantation of the autologous bone marrow taken in young age considerably retards the atherosclerosis development. Inhibition of atherogenesis is also achieved by introduction (to animals) of natural thymic vilosene preparation which compensates a decrease in the functional activity of the thymus gland occurring under conditions of experimental hyperlipidemia. PMID- 2591582 TI - [Functional status, myocardial metabolism and immunologic shifts in experimental myocardial infarction and its treatment with cyclophosphamide and 6 mercaptopurine]. AB - The influence of cyclophosphamide immunodepressants and 6-mercaptopurine on the electrocardiogram shifts, myocardial metabolism and humoral and cellular immunity indices has been studied on the dogs with experimental infarction. The results of the investigation show the incongruity to use cyclophosphamide immunodepressants and 6-mercaptopurine under myocardial infarction as they inhibit immunological reactivity, deteriorate coronary circulation and myocardial metabolism as well as retard reparative processes in the cardiac muscle. PMID- 2591583 TI - [Antibody-dependent cell cytotoxicity and spontaneous cytotoxicity of peripheral blood lymphocytes of organ recipients and cells infiltrating the kidney allogeneic transplant]. AB - It is supposed that determination of antibody-dependent cellular-mediated cytotoxicity and spontaneous cellular-mediated cytotoxicity in the peripheral blood is non-informative for early diagnosis of acute rejection crisis. Activity of K- and NK-cells in peripheral blood is observed to increase during a peak of the rejection crisis. While studying cellular infiltrate obtained from the transplanted kidney, activity of K- and NK-cells is shown to considerably increase in the rejected transplants, which can testify that they contribute much in the loss of the allotransplant function. PMID- 2591584 TI - [Hyperkalemic normothermic hypoperfusion of the isolated heart]. AB - It is established that both normothermic hypoperfusion of the heart by cardioplegic solution and pharmacocardioplegia with cold protect myocardium from the ischemic damage. PMID- 2591585 TI - [Effect of replacement of air nitrogen by inert gases on oxygen consumption by the liver tissues in albino rats on various fatty diets]. AB - The effects of helium and argon, inert gases, on oxygen consumption have been studied on liver tissue of white rats who were delivered different fatty products plus to basic food). It is shown that the effects of helium and argon on the tissue respiration depend on the nature of fatty products. The role of membrane structure in realization of the influence of inert gases on tissue respiration is under discussion. PMID- 2591586 TI - [Characteristic of gastric response to acute and chronic stress and to their combination]. AB - Experiments on 39 rats subjected to the effect of acute, chronic stresses and to that of their combination have revealed a parallelism between the degree of the ulcerogenic effect and depression of antioxidant activity of the stomach tissue cells. PMID- 2591587 TI - [A method of studying variations in the common center of gravity (stabilometry)]. AB - A procedure to study variations of the common human centre of gravity (stabilometry) permits using a principle of a biological feedback. It is achieved by application of a device to study the nervous system. A procedure is recommended to be widely used in applied physiology. PMID- 2591588 TI - [The role of cholinergic receptors in the reactions of the hemostasis system to vasopressin]. AB - Participation of central and peripheral++ cholinoreceptors in responses of blood coagulation system to intravenous vasopressin injection has been studied in experiments on white rats. Vasopressin was injected in combination with atropine and metacine Intensification of the procoagulant activity, that was observed 15 min after vasopressin injection (4 micrograms/kg), was practically retained during cholinergic blockade. The intensification of fibrinolytic activities as a result of an increase in the level of plasminogen activators in blood, is to a great extent blocked by atropine rather than by metacine. Consequently, to intensify the procoagulant activity without changes in fibrinolysis (for example hemophilia) it is necessary to use the vasopressin injection in combination with atropine. PMID- 2591589 TI - [Thoughts on the rate of training of dentists as well as the total number of dentists in Hungary]. AB - The rate of the education of dentists and the trend of the number of dentists from 1938 until present days are analysed. Due to the imminent social changes the number of dentists has not met the demand. The merits of Karoly Toth in realisation of the decentralization of the training of dentists and in rational forming of the development thereof is emphasized. Attention is called to the co ordination of instructive and receiving places, and to the necessity of establishing regional faculties of dentistry. PMID- 2591590 TI - [Teaching propedeutics of conservative dentistry]. PMID- 2591591 TI - [The condition of the permanent teeth of students 15 to 17 years of age in secondary schools in Csongrad County]. AB - The teeth of altogether 1253 students studying in 38 secondary educational establishments of the County of Csongrad have been examined. The number of the examined amounts in case of the 15 years old to 13.51% and in case of the 17 years old to 8.8% of the total number of youth of similar age living in the County. The caries frequency is 98.95% at the age of 15 years, and 98.78% at the age of 17 years. The DMF-T index is 10.35 for the 15 years old, and 10.93 for the 17 years old. With respect to the DMF-T indices found with people of the same year in Szeged in 1961 the present data are higher by 39.11% (15 years old) and by 29.66% (17 years old), respectively. PMID- 2591592 TI - Focal congenital anomalies of the retinal pigment epithelium. AB - The terms, 'hamartoma', 'choristoma', 'phacoma' (mother-spot), and 'naevus', are used to describe benign developmental tumours or placoid lesions. Stedman's Medical Dictionary defines a hamartoma as: 'A focal malformation that resembles a neoplasm grossly and even microscopically, but results from faulty development in an organ; it is composed of an abnormal mixture of tissue elements, or an abnormal proportion of a single element, normally present in that site, which develop and grow at virtually the same rate as normal components, and are not likely to result in compression of the adjacent tissue (in contrast to neoplastic tissue).' A choristoma is defined as 'a mass formed by maldevelopment of tissue of a type not normally found at that site.' Phacoma is defined as, 'a hamartoma found in phacomatosis,' a group of hereditary diseases characterised by hamartomas of multiple tissues. A naevus is a, 'birthmark; a circumscribed malformation of the skin, especially if coloured by hyperpigmentation or increased vascularity; it may be predominantly epidermal, adnexal, melanocytic, vascular, or mesodermal, or a localised overgrowth of melanin-forming cells arising in the skin early in life.' Ophthalmologists have adopted the term to refer to developmental melanocytic lesions of the uveal tract, but heretofore have not used it to describe developmental melanocytic, glial, or vascular lesions of the retina. The purpose of this report is to summarise the author's observations and concepts concerning focal lesions that probably are developmental tumours and placoid lesions composed of either entirely or in part retinal pigment epithelium (RPE). Two of the lesions are tumefactions and may properly be termed 'hamartomas'. Four of the lesions are placoid and might better be described as naevi. Two are composed of hypertrophied RPE cells engorged with melanin granules, one is presumed to be hypertrophied RPE cells filled with a white pigment of unknown nature and one is composed of RPE cells containing no pigment. Three are widely recognised, three others are not. PMID- 2591593 TI - Retinal compression folds after surgery for acute bullous retinal detachment. PMID- 2591594 TI - Retinal patching: a new approach to the management of selected retinal breaks. AB - Restoration of retinal continuity by a patching technique is proposed as a new means of treating selected rhegmatogenous retinal detachments where established techniques frequently fail. The patch consists of a substrate and adhesive applied to the inner surface of the retina surrounding the retinal break. Bovine eye cup experiments have been performed to explore the effectiveness of a range of adhesives, and cyanoacrylates and Tisseel have been found to be effective. Studies of these adhesives on confluent cultures of bovine retinal pigment epithelial cells and glia revealed temporary cyanoacrylate toxicity and stimulation of proliferation by Tisseel. Substrate biocompatability was investigated by observing the growth of cells on various substrates in tissue culture; biological substrates such as lens capsule supported cell growth whereas synthetic membranes only did so if pretreated with fibronectin. PMID- 2591595 TI - Transplantation of retinal pigment epithelium using a pars plana approach. AB - We describe a pars plana approach for transplantation of autologous retinal pigment epithelial cells from a peripheral chorioretinal biopsy to prepared Bruch's membrane at the posterior pole of the same eye. The technique has potential application in research and could be clinically applicable in the treatment of senile macular degeneration. PMID- 2591596 TI - Laser treatment of retinal angiomatosis. AB - We have treated 26 retinal angiomas of less than 4.5 mm in size in 15 eyes using repeated applications of contiguous argon blue green laser burns. All except one of the angiomas regressed without a massive exudative response of treatment. Haemorrhage occurred in two cases but only affected the visual outcome in one eye. Traction retinal detachment persisted in 50% of the large angiomas, despite regression of the tumour. PMID- 2591597 TI - Responses of the retinal circulation to systemic autonomic stimulation in diabetes mellitus. AB - The retinal vessel calibre responses to systemic sympathetic stimulation, were studied in 22 randomly selected diabetic patients (mean age +/- SEM: 54.7 +/- 2.59 years, range 25-73; 13 IDDM, 9 NIDDM; 4 females), using sustained isometric muscle contraction as the stimulus. At a different session the integrity of the autonomic nerve function in these diabetic patients was assessed using 3 standard tests of autonomic nerve function, based on cardiovascular reflexes. Diabetic patients with an intact autonomic nervous system: Group 1, (n = 11, mean age: 54.9 +/- 4.55 years, 7 IDDM 4 NIDDM) showed a mean arteriolar constriction of 9.2% (SEM 2.89, p less than 0.01) and a mean venule constriction of 5.1% (SEM 1.73, p less than 0.02), for a mean rise in diastolic blood pressure of 23.7 mmHg (SEM 2.19 range: 13-33). There were no significant mean retinal vessel responses however, in diabetics with autonomic dysfunction (Group 2): mean arteriolar constriction of 1.2% (SEM 1.38 p greater than 0.05) and venule constriction of 2.1% (SEM 1.38, p greater than 0.05); for a mean rise in diastolic blood pressure of 19.8 mmHg (SEM 4.49, range: 2-50). There was no correlation between the rise in diastolic blood pressure and the retinal arteriolar constriction in the 2 groups (Group 1:r = 0.45, p greater than 0.01 and Group 2: r = 0.56, p greater than 0.05). Duration, type and control of diabetes were not significantly different between the 2 groups. The severity of retinopathy was slightly worse in Group 2 compared to Group 1. These results point to an association between autonomic neuropathy and failure of regulation of retinal blood flow. PMID- 2591598 TI - Large corneal grafts can be successful. AB - Seventeen grafts of 10 mm in diameter or larger have been performed on 16 eyes of 15 patients. The major indications for surgery were infections or perforations or both. Follow-up has ranged from 8-54 months (mean 26.4). The 4 year survival probability was 0.64. Although the procedure was successful in saving all but one eye and restored useful vision in the majority, complications including cataract, glaucoma, graft rejection episodes and infections were encountered. The management of these complications is described. At final review, 13 eyes had clear grafts including those in whom regraft had been performed. These results have only been achieved by close co-operation between patients and the medical team responsible for their care. PMID- 2591599 TI - The use of a biological adhesive to achieve sutureless epikeratophakia. AB - An adhesive made of concentrated human fibrinogen produced from samples of single donor blood by a simple cryoprecipitation method was tested for its ability to bond lamellar corneal buttons in vitro and found to have a bond strength of 140 gm/cm2. The adhesive was successfully used to attach experimental epikeratophakia grafts in a rabbit model. The results were similar to those reported from an earlier trial using a commercially available adhesive prepared from pooled multi donor human plasma. This experimental trial of single-donor adhesive demonstrates the possibility of successful use of autologous fibrinogen adhesive in human epikeratophakia. Autologous adhesive would remove the possible threat of transmitted disease posed by multi-donor adhesive and avoid immune reactions to foreign proteins. PMID- 2591600 TI - Ocular and facial maldevelopment: the role of neural crest. AB - Three children are described who show a spectrum of clinical abnormalities affecting their eyes and non ocular tissues. These entities are best explained as disorders of neural crest migration and once recognised should lead to a search for other systemic developmental disorders. The mechanism of combined facial skeleton and eye malformation is discussed in the light of our current understanding of ocular embryology, and the justification for considering these and other entities as examples of Neurocristopathies is explored. PMID- 2591601 TI - Immunomodulation of experimental autoimmune uveitis using a rat anti retinal S antigen specific monoclonal antibody: evidence for a species difference. AB - Experimental Autoimmune Uveitis (EAU) induced by retinal antigens, particularly S antigen, forms a useful model of human chronic intraocular inflammation particularly endogenous posterior uveitis. It provides a means of assessing the efficacy of various agents used in the control of such inflammation. We induced an autoimmune uveitis and its associated pinealitis in Dunkin-Hartley guinea pigs and Lewis rats by inoculating them with bovine retinal S-antigen. In rats, induction of EAU but not of Experimental Autoimmune Pinealitis (EAP) could be prevented by the administration of S-antigen specific rat monoclonal antibody simultaneously with the S-antigen. Inhibition of EAU was accompanied by significantly raised levels of anti-S antibodies during the first two weeks post immunisation. In contrast, the same monoclonal antibody failed to inhibit both EAU and EAP in guinea pigs. Immunocytochemical staining of rat tissues for lymphocyte subsets, monocytes and macrophages showed that eyes of monoclonal antibody treated animals contained no immunocompetent inflammatory cells unless they also had clinical signs of inflammation. In contrast, the inflammatory exudate in the pineal glands of both treated and untreated animals contained equal numbers of infiltrating lymphocytes and monocytes in the same relative proportions. These results indicate that the inhibitory effect of the monoclonal antibody S2.4.C5 is directed towards the effector arm of the immune-mediated cytotoxic response. A possible mechanism by which the antibody may be preferentially inhibiting the inflammatory response in the eyes but not in the pineal glands of rats, is suggested. PMID- 2591602 TI - Probing visual function with psychophysics and photochemistry. AB - New methods using computer based measurements and image analysis techniques can improve and expand our ability to investigate non-invasively the function of the retina in patients. These can provide insight into the underlying mechanism of an abnormality and further our understanding of disease processes. PMID- 2591603 TI - [Pregnancy induced hypertension (PIH) and osteoporosis]. AB - The authors have already reported that the bone density of normal pregnant women might be kept at the same density as in normal non-pregnant women. However, it might be decreased in women with pregnancy induced hypertension (PIH) by estimating serum calcium levels, serum levels of calcium regulating hormones and calcium secretion into the urine. In order to demonstrate this theory, the degree of bone density in the second metacarpal bone of normal or PIH pregnant women was measured by X-ray using microdensitometry method (MD method). In MD method, six indices, such as MCI, d, GSmin, GSmax, sigma GS/D and densitometric pattern, are calculated by computer analysis of the X-ray of the bilateral hands. By the evaluation of the degree of bone atrophy, scores such as 0 better than the regression line of healthy women, which were prepared according to each age, 1 until 1 delta to the aggravation, 2 until 2 delta, and 3 more than 2 delta were totaled and evaluated as normal, initial stage of bone atrophy, 1st degree of bone atrophy, 2nd degree of bone atrophy and 3rd degree of bone atrophy for 0-3 scores, 4-9 scores, 10-12 scores and 13-18 scores, respectively (delta = 1 S.D.). The metacarpal index (MCI) of normal pregnant women in 3rd trimester was more than the mean in all cases, while cases more than 2 delta of the mean were noted in 29.4% of mild PIH and 11.8% of severe PIH, and a decreasing tendency of width of bone cortex was considered in PIH women. On the other hand, width of bone marrow (d) increased significantly in mild and severe PIH women. In the index for the density of only bone cortex area (GSmax) in PIH women, cases less than mean 1 delta were noted in 29.3% of mild types and in 11.8% of severe types respectively, and a high incidence was noted even though it was insignificant compared with 7.4% of normal pregnant women. In the index of the densities of bone cortex and bone marrow (GSmin), cases less than mean -1 delta were noted more frequently in PIH women than normal pregnant women, but in the index of bone density per unit length (sigma GS/D) no differences were noted between PIH and normal pregnant women.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2591604 TI - [The effect of cholecystokinin antagonists on satiety induced by cholecystokinin octapeptide in dogs]. AB - We administered two cholecystokinin antagonists to dogs intravenously (i.v.) and into the third cerebral ventricle (i.t.v.). Proglumide (3-300mg/kg/hr i.v. or 0.1 10mg/dog i.t.v.) reversed the satiety previously shown by mongrel dogs after i.t.v. CCK-8. A new glutaramic derivative, CR1409, blocked this satiety even more strongly when administered by either route. Proglumide increased proglumide levels in ventricular fluid, indicating its ability to cross the blood-brain barrier. However, i.t.v. proglumide did not appear in the blood during the observation period. These results suggest that systemic proglumide and CR1409 act as antagonists of the central CCK receptor concerning satiety in dogs; intravenously administered proglumide was found to cross the blood-brain barrier and partially but significantly reverse the satiety caused by CCK-8. PMID- 2591605 TI - [The effect of prostaglandin D2 on rat testicular testosterone levels]. AB - In vivo effects of prostaglandin D2 (PGD2) on rat testicular testosterone levels were studied. Testosterone levels were determined by HPLC after 6 hours of PGD2 and of hCG. The testosterone levels were decreased by dose of 500 micrograms/rat intraperitoneal injection. Testis testosterone levels were subsequently decreased by intratesticular injection with PGD2 (1.0 micrograms) into the right testis. The left testis received vehicle alone for control. The increase in testosterone levels induced by hCG (50, 100 and 500 unit/rat s.c.) were also inhibited by intraperitoneal injection of 500 micrograms of PGD2. On the other hand, intratesticular injection of hCG (0.01, 0.1 and 1.0 unit/testis) caused an increase in testosterone levels according to dose of hCG. The increase in testosterone levels by hCG was inhibited by simultaneous injection of PGD2 (1.0 micrograms/testis). These results suggest that PGD2 may play an inhibitory action on LH action in androgen synthesis in the rat testis. PMID- 2591606 TI - [Graves' disease with unusual histological findings]. AB - We reported three cases of Graves' disease which showed unusual histological findings featuring solid follicles, multinucleated giant cells and diffuse infiltration of histiocytes as well as lymphocytes in the whole section of the resected thyroid. Characteristics of these three cases were as follows: (1) Clinically, longer duration of the disease and exophthalmos were their prevailing findings. (2) On laboratory data, antimicrosomal antibody showed extremely high titers with 100,000 to 400,000. (3) Their operative findings were different from ordinary Graves' goiters in that colors of the goiter were yellow-red or gray red, surface was rough and coarse, consistency was firm, and adhesions with the adjacent connective tissue were noted. (4) Postoperative clinical outcome was quite similar to that of ordinary Graves' patients. From these findings, these three cases were considered to be different from either so-called Hashitoxicosis or silent thyroiditis or Graves' disease with granulomatous foci, and it was suggested that these three cases might be a subgroup of Graves' disease or another hyperthyroidism than ordinary Graves' disease. Further accumulation and analysis of such cases will be necessary in order to answer this question. PMID- 2591607 TI - [An autopsied case of insulin dependent diabetes mellitus complicated by chronic thyroiditis and chronic hepatitis]. AB - A deceased 59-year-old woman with insulin dependent diabetes mellitus complicated by chronic thyroiditis and chronic hepatitis was autopsied. She had had diabetes mellitus since she was 30 years old, and insulin therapy was started at 34 years. Laboratory findings were as follows: s-GOT 85, s-GPT 31, gamma-globulin 2.45 g/dl. Immunological tests were positive for anti-smooth muscle antibody and anti ENA antibody with high titers of antithyroglobulin and anti-microsome antibodies. HLA analysis revealed the presence of DR-4. The thyroid biopsy specimen showed microscopic features characteristic of chronic thyroiditis at 52 years of age. She had been repeatedly admitted for the control of diabetes mellitus. She was admitted for the 9th time in June, 1987 following complaints of abdominal pain. After admission, her general condition became gradually worse, and she died of peritonitis in September, 1987. Pathological examination of the liver revealed an expansion of fibrous tissue on Glisson's capsule accompanied by lymphocytic infiltration and was diagnosed to be chronic inactive hepatitis. As for the thyroid gland, fibrous tissue replaced an extensive area of the thyroid gland, and normal thyroid tissue was not observed. Lymphocytic infiltration was less in comparison with that in the previous biopsy. As for the pancreas, atrophy of exocrine pancreatic tissue and fibrous change in interstitial tissue was observed. Lymphocytic infiltration was also seen in the interstitial exocrine tissue but not in the islet. Immunohistochemical examination of the islets using anti-insulin, glucagon and somatostatin antibodies by ABC peroxidase method showed the selective disappearance of B cells in the islets. The pathological changes in the thyroid gland, liver and pancreas suggest that autoimmune mechanism may be involved in the pathogenesis of chronic thyroiditis, chronic hepatitis and IDDM with exocrine pancreatic impairment in this case. PMID- 2591608 TI - [Two cases of Graves' disease with anti-thyroid hormone autoantibodies: the effect of subtotal thyroidectomy on the titers of anti-thyroid hormone autoantibodies and anti-Tg antibodies]. AB - We experienced two cases of Graves' disease associated with anti-thyroid hormone autoantibodies (Case 1: anti-T4, Case 2: anti-T3). Both cases underwent subtotal thyroidectomy, and titers of anti-thyroid hormone antibodies and anti-Tg antibodies were compared before and after operation. In case 1, titers of both anti-T4 and anti-Tg antibodies decreased after operation, whereas in Case 2, titers of both anti-T3 and anti-Tg were unchanged before and after operation. There was a significant positive correlation between titers of anti-T4 and anti Tg antibodies in Case 1 (r = 0.90, P less than 0.01), and anti-T3 and anti-Tg antibodies in Case 2 (r = 0.64, P less than 0.01). These results strengthen the possibility that the antigen of anti-thyroid hormone autoantibodies in both cases is the Tg molecule. PMID- 2591609 TI - [The effect of 1,25(OH)2D3 on bone mineral content in senile osteoporosis--a dose finding study]. AB - In order to clarify the effect of 1,25(OH)2D3 on the bone mineral content in senile osteoporosis, we examined the radial mineral density in 41 female cases of senile osteoporosis treated with 1,25(OH)2D3. The diagnostic criteria of senile osteoporosis were as follows. 1) Radial mineral density at below 0.5 g/cm2 by SPA 2) Bone dystrophy score in vertebra at over I degree 3) Presence of vertebral fracture 4) Over 60 years of age The subjects were divided into 5 groups: a control group (n = 11), a 0.25 microgram of 1,25(OH)2D3 once-a-day group (n = 5), a 0.5 microgram of 1,25(OH)2D3 once-a-day group (n = 8), a 0.25 microgram of 1,25(OH)2D3 twice-a-day group (n = 8) and a 0.25 microgram of 1,25(OH)2D3 three times-a-day group (n = 9). There was no significant difference in background data among these groups except for serum Al-P activity. The radial mineral density was measured in these 5 groups before and every 3 months after, starting the treatment by single photon absorptiometry in 1/3 distal site of radius for 1 year. No significant difference was detected in the serum levels of Ca, Pi and Al P activity after starting the treatment among the 5 groups. The area under curve (AUC) of the radial mineral content after the treatment was calculated in each group. There was a significant dose-related increase in the AUC (p less than 0.05). However, the urinary Ca/Cr ratio was increased in the group receiving 0.75 microgram/day of 1,25(OH)2D3 The final AUC in the group receiving 0.5 microgram/day of 1,25(OH)2D3 tended to be very high compared with that in the other groups. From the above, it was suggested that 1,25(OH)2D3 might be effective for the treatment of senile osteoporosis especially at the dose of 0.5 microgram/day. PMID- 2591610 TI - [Graves' disease with markedly elevated serum immunoglobulin E]. AB - A 37-year-old female with Graves' disease was reported. An abnormally high concentration of serum IgE was observed by radioimmuno-sorbent test before treatment. Laboratory findings showed no evidence of atopic diseases or other known diseases with hyperglobulinemia E. There is no reported case of Graves' disease associated with remarkably elevated plasma IgE level. In the present patient, a further elevation of serum IgE concentration was observed when the dose of methimazole reached about 500 mg in total. Allergic mechanism may be the cause of this phenomenon. Serum IgE level was decreased gradually after replacement of methimazole by propylthiouracil. IgE level was not parallel with thyroid functions, and even when her thyroid function was normalized after subtotal thyroidectomy, IgE concentration was still increased around 900 IU/ml. The mechanism of hyperglobulinemia E in this case was discussed. PMID- 2591611 TI - [Midluteal progesterone/estradiol ratio as an indicator of pregnancy potential]. AB - In an effort to determine the reliability of the midluteal progesterone(P)/estradiol(E2) ratio as an index of the potential for conception, we measured the midluteal P and E2 levels in 76 infertile women who had been treated at our infertility clinic. This parameter in conception cycles was compared with that in non-conception cycles. Eighty cycles of the 76 women were classified into two groups, depending upon whether pregnancy occurred or not. Group 1 and group 2 were composed of 31 conception cycles and 49 drug-induced cycles, respectively. Midluteal concentrations of P and E2 did not show any significant differences between the two groups. The P/E2 ratios were 106.4 +/- 71.3 (mean +/- SD) and 71.5 +/- 44.16, respectively. This difference was statistically significant (p less than 0.05). Discriminant function analysis showed that the smallest probability of misclassification between the two groups decreased from 44% when using P only to 36% when using the combined P and E2. The following equation: Y = 0.0727X1 - 0.00456X2 - 0.130 was obtained (when X1 = P, X2 = E2). These results suggest that the midluteal P/E2 ratio gives clinicians the best indication of luteal function for the achievement of pregnancy. PMID- 2591612 TI - [A case report of Refetoff's syndrome]. AB - An 11-year-old girl with diffuse goiter is presented. She had no clinical evidence of thyrotoxic symptoms or signs of palpitation, excessive sweating, tachycardia or finger tremor. Both the serum T4 (24.0 micrograms/dl) and T3 (282ng/dl) were high, and thyroid 131I uptake rate (63.2%) was significantly elevated, but T3/T4 ratio was not elevated (11.8). BMR was measured three times and remained within normal limits. Her serum TSH was 1.9 microU/ml, and a TRH stimulation test resulted in a normal rise of serum TSH (13.4 microU/ml). The TSH secretion was not suppressed by medication (p.o.) of 75 micrograms of L triiodothyronine given for 8 days. The autoantibodies of T4, T3 and TSH were negative. No sign of pituitary tumor was observed by plain X-ray film. No defect in her sight-field was found. From these clinical figures and data, Refetoff's syndrome was suspected. She was eumetabolic without any treatment, but the goiter gradually enlarged and dysphagia developed. A large dose of L-thyroxine (450 micrograms/day) was given for a period of one year and four months. She has been eumetabolic. Her goiter disappeared and the dysphagia completely subsided. After she was given large doses of L-T4, her serum TSH was reduced to 0.07 microU/ml and was slightly elevated to 0.24 microU/ml at 30 min after i.v. infusion of 500 micrograms TRH. Thyroid 123I uptake rate was suppressed to 8.3%. According to Refetoff's papers, this case was classified as being in the group with generalized resistance to thyroid hormone. PMID- 2591613 TI - [62d fall meeting of the Japan Endocrine Society. 20-21 October 1989, Sapporo. Abstracts]. PMID- 2591614 TI - [Erythema elevatum diutinum--a rare variant of skin changes in systemic lupus erythematosus]. AB - It is reported on 5 patients with erythema elevatum diutinum, in 2 of these cases exists a systemic lupus erythematosus and another patient suffers from cutaneous lupus erythematosus. This information can be considered as a possibility that cutaneous alterations similar to erythema elevatum diutinum could be the first symptoms of systemic lupus erythematosus when the usual treatment is inefficient. PMID- 2591615 TI - [Methodologic aspects in cultivating human keratinocytes]. AB - The cultivation of human keratinocytes is an appropriate experimental model for a variety of cell biological, pharmacological and biochemical investigations and the production of in vitro epidermis suitable for grafting since Rheinwald and Green (1975) have established this method. A procedure is described to isolate and culture human keratinocytes using different culture conditions. About 1-2 million epidermal cells could be prepared by trypsinization over night at 4 degrees C from 1-2 cm2 skin. Primary cell cultures seeded on mitomycin C treated NIH 3T3 fibroblasts reached subconfluence after 15-20 days when Eagle MEM was used as culture medium and after 10-15 days of culture using a mixture of Dulbecco's MEM and Ham F12 (3:1). In each case the media were supplemented with different growth factors. Subcultures were seeded on NIN 3T3 feeder cells as well as in collagen or fibronectin coated dish. Multilayered epidermal sheets developed with in 12-15 days of culture. PMID- 2591616 TI - [Pili anulati]. AB - Report on a 10 year-old girl with pili anulati. Clinical and microscopical findings of that maldevelopment of hair are described. Interestingly, an episodical alopecia totalis and subsequent regrow exhibiting different hair color was observable. Genealogical search confirmed autosomal dominant genetics. The question of expressivity of that dominant gen is discussed. PMID- 2591617 TI - Hypotrichosis with keratosis pilaris: electrophoretical study of hair fibrous proteins from a patient. AB - S-carboxymethylated (SCM) fibrous proteins from the scalp hair of a patient with hypotrichosis with keratosis pilaris (HTKP) and from that of a normal individual were analyzed using two-dimensional electrophoresis. One SCM fibrous protein component was different electrophoretically in the HTKP patient. It is suggested that the brittleness of the HTKP hair might result from this alteration of the fibrous protein composition of the hair. PMID- 2591618 TI - Frequency of acquired melanonevocytic nevi and their relationship to skin complexion in 939 schoolchildren. AB - In 939 schoolchildren aged 8-16 years skin complexion was determined by a system of seven categories Anamnestic data concerning tanning ability and history of sunburns, however, were not considered owing to their obvious unreliability in children. Mean nevus count was 17.97, was significantly higher in boys than in girls and increased with age. There was a clear relation of mean nevus number and skin complexion: in fair skin type nevi are most frequent, decreasing in number by increasing of pigment content. Additionally, children with freckles have higher mean nevus count in every category of skin complexion. All literature data critically reviewed as dealing with mean mole count are not comparable in several respects. In different races, however, such studies may serve as a basis for subsequent investigations concerning the questions of probably increasing number of melanonevocytic nevi. PMID- 2591619 TI - Linear pemphigus vulgaris after X-ray irradiation. AB - The authors report the case of a 64-year-old female with a pemphigus vulgaris that relapsed on her left cheek following X-irradiation. The lesion developed not only on the irradiated area but also along a linear streak. Blaschko lines seem to represent the linear systematization pattern more likely to account for this unusual distribution. PMID- 2591620 TI - Vitiligo and topical allergens. PMID- 2591622 TI - Graves' ophthalmopathy: developments in diagnostic methods and therapeutical procedures. International workshop. Homburg/Saar, October 7, 1987. PMID- 2591621 TI - [Proceedings of the Belgian Society for Dermatology and Syphiligraphy. Brussels, 19 March 1988. Case reports]. PMID- 2591623 TI - Unusual motility impairment in endocrine orbitopathy. PMID- 2591624 TI - Reduction by orbital radiation of cumulative doses of glucocorticoids in patients with Graves'-Basedow ophthalmopathy. PMID- 2591625 TI - Surgical repair of motility impairment in Graves' orbitopathy. PMID- 2591626 TI - Orbital decompression surgery. PMID- 2591627 TI - Graves' ophthalmopathy: standardized evaluation of computed tomography examinations; magnetic resonance imaging. PMID- 2591629 TI - Standardization and evaluation of clinical findings in patients suffering from Graves' ophthalmopathy. PMID- 2591628 TI - Pathogenesis of thyroid-associated ophthalmopathy. PMID- 2591630 TI - Effect of near total thyroidectomy on ophthalmopathy in patients with Graves' disease. PMID- 2591631 TI - Plasma exchange therapy for severe Graves' ophthalmopathy. PMID- 2591632 TI - Treatment of Graves' ophthalmopathy with new immunosuppressive agents. PMID- 2591633 TI - Purification and characterization of a calf thymus protein active on lipid metabolism. AB - 1. This work concerns the purification of a calf thymus protein that increases the binding of human 125I-labeled low density lipoprotein (LDL) on both human skin fibroblasts and a special line of rat liver cells, BRL 3A. 2. It was found that the thymus gland affects cholesterol metabolism via an activation of the LDL receptor pathway. 3. Moreover, the thymus protein active on the LDL receptor pathway has a different amino acid composition and molecular weight from other well-characterized thymic peptides. PMID- 2591634 TI - Coordinate elevations of liver delta-aminolevulinate synthase and cytochrome P 450 RNA by phenobarbital in chicken embryos: the effects of heme. AB - 1. The role of heme in the coordinate elevations of liver delta-aminolevulinate (ALA) synthase activity and microsomal cytochrome P-450 concentration induced by phenobarbital (PB) was investigated in the chicken embryo. 2. Eighteen day old chicken embryos were given PB, and the changes in liver content of PB-inducible cytochrome P-450 RNA and of ALA synthase RNA were determined at different times after exposure to the drug. 3. The concentrations of both types of RNA increased rapidly after PB administration, and by 9 hr the level of ALA synthase RNA was 55 fold higher than control and that of cytochrome P-450 RNA was 7-fold higher than normal. 4. While the rate of increase in ALA synthase activity paralleled closely that of the enzyme's RNA concentration, the rate of increase of spectrally active cytochrome P-450 concentration in microsomes lagged behind that of the apoprotein's RNA by several hours. 5. To test whether heme depletion was responsible for the coordinate inductions of the two enzymes, embryos were loaded with ALA 2 hr before exposure to PB. 6. The protocol led to a drop in the PB inducible ALA synthase RNA concentration and to an increase in that of cytochrome P-450 RNA, measured 6 hr after drug administration. 7. In primary cultures of hepatocytes, hemin in the culture medium caused a modest drop in ALA synthase RNA concentration but had a variable effect on that of cytochrome P-450 RNA in cells incubated with PB for 9 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591635 TI - DNA homology of surface protein antigen A gene in mutans streptococci. AB - 1. A recombinant plasmid, pYA724, containing an 8.45 kb DNA fragment encoding surface protein antigen A (spaA) from Streptococcus sobrinus 6715 was used to examine the DNA homology of the spaA gene with chromosomal DNA of various mutans streptococci strains. 2. Restriction endonuclease BamHI-digested pYA724 DNA was radio-labeled by nick-translation, and a DNA-DNA hybridization experiment was carried out. pYA724 DNA hybridized with chromosomal DNA of serotypes a, c, d, e, f and g strains, but not with b by dot DNA-hybridization and Southern blot DNA hybridization. 3. Chromosomal DNAs were isolated from several serotype c Streptococcus mutans strains, digested with BamHI, and analyzed by Southern blot DNA hybridization. pYA724 DNA hybridized with different sizes and numbers of BamHI-digested DNA fragments of the chromosomal DNAs. 4. These data indicated that all mutans streptococci strains except serotype b have DNA homologous with the spaA gene, although within the same serotype strain the spaA gene has a diversity of arrangement within the chromosome. PMID- 2591637 TI - Transport studies with brush border membrane vesicles: choice of experimental parameters. AB - 1. We have studied different parameters, in their effects on a transport system chosen as a model: the Na+-phosphate symporter of the renal brush border membrane. 2. Ionic strength was found to be a critical factor in the retention capacity of the filter. 3. When high ionic strength solutions containing 150 mM NaCl or KCl were used, less than 8% of the membrane proteins were lost through filtration. 4. Lowering the ionic strength by replacing NaCl or KCl by 300 mM mannitol, however, caused a 52% loss of protein. 5. Addition of 15 mM NaCl to this low ionic strength solution was sufficient to restore full retention of the vesicles by the filter. 6. The presence of arsenate, a competitive inhibitor, in the stop solution did not improve the retention of phosphate by the vesicles in high ionic strength media, but caused a pronounced temperature dependent loss of the vesicle content, as a function of time of incubation in low ionic strength solutions. 7. Addition of 5 mM phosphate in the stop solution caused a 31 and 37% loss for KCl and NaCl stop solutions, respectively, while no effect was observed for the mannitol stop solution. 8. The presence of HgCl2 gave a 32% stimulation for the mannitol solution and a 35 or 22% inhibition for the KCl or NaCl solutions. 9. Addition of NaCl in the stop solution caused an overaccumulation of 75%, after 60 sec of incubation at 25 degrees C. 10. Phosphate transport by renal vesicles is thus highly affected by the composition of the stop solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591636 TI - Purification and properties of pyruvate kinase type M1 from bovine brain. AB - 1. Pyruvate kinase type M1 was purified from bovine brain about 241-fold with 38% yield. 2. Specific activity of the enzyme was above 217 U/mg of protein (25 degrees C), relative mol. wt of the subunit--57,000 (+/- 2000) and pH optimum- 6.8-7.2. 3. The enzyme shoved hyperbolic kinetics with Km value for PEP of 0.04 mM and for ADP of 0.3 mM. 4. Inorganic phosphate and ATP at concentrations below 4 mM showed activating effect, 1-phenylalanine and ATP above 6 mM--an inhibiting effect on the enzyme. 5. Inhibition by 1-phenylalanine was prevented by fructose 1,6-bisphosphate. PMID- 2591638 TI - A new approach of the estimation of Km of carbamyl phosphate synthetase for ammonia in isolated rat hepatocytes. AB - 1. The Km for ammonia of carbamyl phosphate synthetase was determined by preincubating isolated liver cells for 30 min in the absence of ammonia and bicarbonate and in the presence of ornithine, chloroquine, which blocks lysosomal proteolysis, and aminoxy acetic acid, which inhibits transaminases. 2. The reaction was started with the addition of varying concentrations of ammonia and 10 mM bicarbonate. 3. The rate of citrulline formation was measured as related to ammonia concentration. 4. The pre-incubation with ornithine permits an accumulation of intracellular and mitochondrial ornithine concentrations which in turn allow rapid citrulline formation in the carbamyl phosphate form. 5. This prevents any feedback inhibition on a carbamyl phosphate synthetase or decreases in activity due to accumulation of carbamyl phosphate and/or absence of ornithine. 6. Using these methods in combination with [14C]bicarbonate permitted an estimation of exogenous ammonia for carbamyl phosphate synthesis. 7. The Km for ammonia was 1.5 mM, using a pK of 8.88 the Km for free NH3 was 48 microM. PMID- 2591639 TI - Further evaluation of cofactor as a turnover label for glycogen phosphorylase. AB - 1. The cofactor of glycogen phosphorylase, pyridoxal phosphate (PLP), is stably associated with the enzyme and has been used as a label in the determination of the turnover of the skeletal muscle enzyme in vivo. 2. Mice were injected with radiolabelled pyridoxine that was subsequently converted to PLP and incorporated into phosphorylase. 3. In this study we have resolved phosphorylase-bound label from that associated with the other PLP-containing enzymes and free label by affinity and size-exclusion chromatography. 4. The decay of radioactive pools was assessed after an extended period post-injection to minimize the effects of isotope reutilization. 5. These modifications have allowed refinement of our previous estimate of the rate of degradation of muscle phosphorylase. PMID- 2591640 TI - Current perception thresholds: a new, quick, and reproducible method for the assessment of peripheral neuropathy in diabetes mellitus. AB - The Neurometer is a variable constant current sine wave stimulator, and has recently been proposed as a simple non-invasive and quantitative measure of peripheral nerve function. The device is portable and battery operated; assessment of upper and lower extremities takes only a few min, in contrast to conventional assessment techniques. In order to assess its potential in the quantification of diabetic neuropathy, detection thresholds for constant current electric sine wave stimulation were measured at three different frequencies in different sites in 31 healthy control subjects and 90 diabetic patients with and without neuropathy. The device provides good discrimination between neuropathic and non-neuropathic groups (p less than 0.001) and is quick and easy to use. Comparisons with results of conventional tests of nerve function show that high frequency detection thresholds correlate best with tests of large fibre function (r = 0.42-0.69, p less than 0.001), and low frequency detection thresholds correlate with tests of small fibre function (r = 0.34-0.46, p less than 0.005). It is concluded that the device may be a simple and comprehensive way of assessing peripheral nerve function. PMID- 2591641 TI - Reduced hyperaemia following skin trauma: evidence for an impaired microvascular response to injury in the diabetic foot. AB - The hyperaemic response to standard needle injury within dorsal foot skin was investigated in normal and Type 1 (insulin-dependent) diabetic subjects using laser Doppler flowmetry. The normal response was maximal within 15 min, localised, prolonged and biphasic. In 20 normal subjects and three groups of long duration Type 1 diabetic patients (20 without complications; 20 with laser treated retinopathy; 15 with neuropathy and retinopathy), the median (interquartile range) peak hyperaemic responses were 1.766 (1.220-1.970), 1.485 (1.342-1.672), 0.997 (0.705-1.203) and 1.030 (0.718-1.369) arbitrary units, respectively. Compared to normal and uncomplicated diabetic groups, peak flow was significantly reduced in the retinopathic (p less than 0.0001) and neuropathic (p = 0.001 and 0.007, respectively) groups. There was no significant difference between the normal and uncomplicated diabetic groups, nor between the retinopathic and neuropathic groups. There was no association of the hyperaemic response with blood sugar, HbA1c, or duration of diabetes. Diabetic patients who have microvascular complications, with or without neuropathy, have an associated impairment of microvascular response to mechanical injury which might predispose to infection and poor wound healing. PMID- 2591642 TI - Increased aortic stiffness in patients with type 1 (insulin-dependent) diabetes mellitus. AB - The biomechanical properties of aortic samples from patients with Type 1 (insulin dependent) diabetes mellitus and age- and sex-matched control subjects were analysed using a materials testing machine. The specimens were prepared from tissue outside areas of visible atherosclerosis in order to discriminate between primary Type 1 diabetic alterations in the aortae and secondary changes due to increased atherosclerosis. We paid special attention to the correction of biomechanical parameters for differences in wall thickness and registration of specimen length values. In the Type 1 diabetic aortae a marked reduction was found in the extensibility and an increase in their stiffness. The reduced extensibility was correlated significantly to the duration of Type 1 diabetes. The pronounced alterations in the mechanical properties could not be explained by the increase in the wall thickness which was observed among the Type 1 diabetic patients and the alterations could not be correlated to the grade of atherosclerosis in the thoracic aorta. The results of the present study, therefore, strongly suggest that Type 1 diabetic patients develop alterations in the arterial connective tissue independent of the presence of atherosclerosis. Such primary alterations in the vessel wall may play a role in the pathogenesis of large vessel disease among these patients. PMID- 2591643 TI - Circulating insulin-like growth factor I in type 1 (insulin-dependent) diabetic patients with retinopathy. AB - The relationship between insulin-like growth factor I (IGF I) and diabetic retinopathy was investigated. This somatomedin circulates bound to at least two large carrier proteins with molecular weights of approximately 150,000 and 35,000. Total and protein binding profiles of insulin-like growth factor I were determined in the serum of 18 patients who had had Type 1 (insulin-dependent) diabetes for 15-20 years, but had no signs of nephropathy and a similar degree of mild subclinical neuropathy. Nine had preproliferative or proliferative retinopathy and 9 had little or no background retinopathy but there was no difference in diabetes duration, insulin doses or glycaemic control between the two groups. In the latter group, the amounts of the somatomedin I and the serum profiles were similar to those in 9 healthy control subjects. In patients with advanced retinopathy, however, binding of insulin-like growth factor I to the carrier proteins was significantly altered. Binding to the low molecular weight protein increased to 140% whereas binding to the large molecular weight protein decreased to 70% of the normal level. In the latter Type 1 diabetic patients total serum insulin-like growth factor I was decreased to 60% of the normal level (p less than 0.02). When the alteration in serum profile was adjusted for, the level of somatomedin associated with the small carrier complex was normal whereas that associated with the large carrier complex was reduced by almost 60% in Type 1 diabetic patients with retinopathy. It is proposed that the total circulating somatomedin level is low in advanced diabetic retinopathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591644 TI - Chronic low frequency electrical activation for one week corrects nerve conduction velocity deficits in rats with diabetes of three months duration. AB - This study examined the effect of chronic electrical activation on conduction velocity deficits after three months of streptozotocin-induced diabetes. There were 30% and 20% reductions in conduction velocity in diabetic animals for tibialis anterior and saphenous nerves, respectively (p less than 0.01). Unilateral electrical stimulation of the common peroneal nerve, which contains axons supplying tibialis anterior but not saphenous nerve, was carried out in a group of diabetic and a group of normal control rats. Stimulation was given over seven days, at 10 Hz for 8 h/day. Final experiments were carried out at least 17 h after the last stimulation session. In normal rats stimulation had no effect on conduction velocity in either nerve. In diabetic animals, however, tibialis anterior conduction was within the normal control range for the stimulated nerve. In contrast, the contralateral unstimulated nerve had reduced conduction velocity (p less than 0.001), which was within the unoperated diabetic control range. There were no effects on saphenous nerve conduction, comparing stimulated and unstimulated legs. We conclude that chronic increases in nerve electrical activation promote mechanisms that reverse conduction deficits in diabetic rats. PMID- 2591645 TI - Abnormal blood rheology and diabetic nephropathy. PMID- 2591646 TI - Is quantitative assessment of insulin-antibodies and autoantibodies feasible? AB - Nine selected sera were studied using radioimmunoassay and enzyme linked immunosorbent assay; eight contained insulin antibodies and were from Type 1 (insulin-dependent) diabetic patients, one of whom had antibody-mediated insulin resistance, and one contained insulin-autoantibodies and was from an asymptomatic blood donor. Sera were assayed in serial dilution to assess their suitability for use as reference standards. Dilution curves were non-parallel in radioimmunoassay but were parallel in immunosorbent assay. In all sera, insulin antibodies were readily detected in both assays whereas the low avidity insulin autoantibodies were only detected by immunosorbent assay and not at all by radioimmunoassay, suggesting that the assays respond differently to antibodies of different avidity. Avidity was estimated in liquid phase from the dissociation rate of preformed complexes of antibody and 125-iodinated insulin. When high avidity antibodies are used as a reference in radioimmunoassay, lower avidity antibodies are underestimated and vice versa. In contrast, in immunosorbent assay, any serum could be used as a reference regardless of avidity; furthermore competition experiments comparing the highest avidity insulin antibodies, from the insulin resistant patient, with the insulin autoantibodies from the asymptomatic blood donor yielded near-superimposable curves. We conclude that radioimmunoassay is selective for high avidity antibodies whereas enzyme linked immunosorbent assay is not; computer modelling of the two assays supports this conclusion. In practice immunosorbent assay can be standardized using a reference serum, whereas experimental findings and mathematical considerations preclude the use of a standard serum in radioimmunoassay. PMID- 2591647 TI - Liver microsomal delta 6 and delta 5 linoleic acid desaturation in female BB rats. AB - Rat liver microsomal delta 6 and delta 5 desaturation are defective in experimental diabetes, but this defect is correctable with insulin treatment. Rat liver fatty acid composition and delta 6 and delta 5 desaturation were studied in the spontaneously diabetic adult female Bio-Breeding (BB) rat. Control Wistar rats and BB rats (4 weeks of diabetes), that received insulin (1 IU.100 g body weight-1.day-1), were killed 20 h after the last insulin injection. delta 6 and delta 5 desaturase activities were estimated from the incubation of liver microsomes with (1-14C) 18:2, n-6 or (2-14C) 20:3, n-6, respectively, and the fatty acid composition of the liver and microsomal liver lipids were investigated. Under experimental conditions delta 6 and delta 5 desaturase activities were unchanged in the BB rats when compared to the control rats. Impairment of the liver fatty acid composition of diabetic BB rats is not consistent with normal desaturase activity and may be explained by factors other than desaturation disturbance. PMID- 2591648 TI - The prevalence of impaired glucose counter-regulation during an insulin-infusion test in insulin-treated diabetic patients prone to severe hypoglycaemia. AB - Among 603 patients over the age of 18, with insulin-treated diabetes mellitus, a questionnaire identified 98 patients who during a 12-month period had experienced severe hypoglycaemia, defined as an event which required the help of another person. Twenty of these patients had repeatedly suffered from such episodes, without any obvious reason, for a period of at least three years. The capacity to counter-regulate a standardized, insulin-infusion test (0.034 U.kg-1.h-1 given for 3 h unless severe neuroglucopenia developed) was evaluated in 14 of these patients. In 12, an impaired glucose counter-regulation was registered, defined as blood-glucose values below -2 SD of healthy subjects. In all but one of these patients, a combined deficiency of glucagon and adrenaline was documented, and was believed to be the likely cause of their inclination towards hypoglycaemia. In patients with severe hypoglycaemia, but not in diabetic patients without severe hypoglycaemia or in healthy subjects, a significant relationship between insulin disappearance and glucose rise was found. It is concluded that in insulin treated diabetic patients, the prevalence of recurrent attacks of severe hypoglycaemia amounts to about 4%. In such patients, a combined deficiency of adrenaline and glucagon responses to hypoglycaemia is the predominant finding and the disappearance rate of insulin becomes critical for recovery of blood glucose after hypoglycaemia. PMID- 2591649 TI - Reduced number of anionic sites is associated with glomerular basement membrane thickening in the diabetic BB-rat. AB - Glomerular basement membranes of diabetic and age- and sex-matched non-diabetic BB rats were studied morphometrically and ultrastructurally using a quantitative histochemical technique employing the cationic dye cuprolinic blue. Six months of diabetes resulted in a significant reduction in the density of anionic sites associated with increased thickness of the glomerular basement membrane. These findings suggest that the loss of anionic sites may be an important mechanism in the genesis of glomerular basement membrane dysfunction in diabetes. PMID- 2591650 TI - [A systems analysis of the accuracy of human reproduction in short time intervals]. PMID- 2591651 TI - [The manifestation of the general properties of the nervous system in the work activity of a punched-card machine operator]. PMID- 2591652 TI - [Occupational reliability of operators of moving equipment]. PMID- 2591653 TI - [Changes in the physical work capacity and the blood biochemical indices of students during an examination session]. PMID- 2591654 TI - [Erythrocytes and the assessment of the physical work capacity of patients with heart valve prostheses]. PMID- 2591655 TI - [The effect of body position on the tolerance for physical loads after long-term hypokinesia]. PMID- 2591657 TI - [Interhemispheric asymmetry as a factor in human adaptation to northern conditions]. PMID- 2591656 TI - [The structure of the response of the human kidneys to water deprivation and water load]. PMID- 2591658 TI - [The effect of adaptation to cold on external respiration indices in hypercapnia]. PMID- 2591659 TI - [The rhythms of the electrical conductivity of human skin]. PMID- 2591660 TI - [Water-salt metabolism during muscle loading in sports of various intensities]. PMID- 2591661 TI - [The adaptation of a psychometric method to the subjective evaluation of memory]. PMID- 2591662 TI - [Characteristics of the formation of evoked potentials]. PMID- 2591663 TI - [The cortical reactivity of the cerebral hemispheres in craniocerebral trauma]. PMID- 2591664 TI - [The functional mobility of the visual analyzer in video installation operators]. PMID- 2591665 TI - [A method for determining the parameters of an equivalent electrical model of the interelectrode area]. PMID- 2591666 TI - [A device for the continuous determination of summary human moisture loss]. PMID- 2591667 TI - [Neuronal bases of the emotional mechanisms of reinforcement]. PMID- 2591668 TI - [Individual characteristics in the functional regulation of the central nervous system]. PMID- 2591669 TI - [Pathophysiologic nature of dissociative states of the brain stem in lesions of the midbrain and the bridge of Varolius]. PMID- 2591670 TI - [The factorial structure of the amplitude indices of the normal bilateral GSR and in schizophrenia]. PMID- 2591671 TI - [Patterns of interrelated changes in the amplitude and frequency of fluctuating components of the heart rhythm]. PMID- 2591673 TI - [Energy expenditures during measured physical loading in healthy men and in patients with ischemic heart disease]. PMID- 2591672 TI - [baroreflex activation of the sympathetic nervous system during a paroxysm of supraventricular tachycardia]. PMID- 2591674 TI - [The relation of the circulatory system reactions to changes in body posture and physical load to the initial level of arterial pressure and heart contraction frequency]. PMID- 2591675 TI - [Regulation of regional circulation in the basins of the common carotid arteries]. PMID- 2591677 TI - [Vasomotor reactions in the muscles of the arms and legs in healthy subjects and in patients with hypertension under a psychoemotional load and in postischemic hyperemia]. PMID- 2591676 TI - [Blood circulation and blood gas composition in various sections of the cardiovascular system in the healthy subject during measured physical loading]. PMID- 2591678 TI - [Contractile properties of the fast and slow muscle fibers in the human crus]. PMID- 2591679 TI - [Fatigue during dynamic and static muscle activity in man]. PMID- 2591681 TI - Animal research versus humane use: the struggle to sustain our research advances. Interview by Edmund Kelly and Anthony Mazzaschi. PMID- 2591680 TI - [The dependence of human work capacity on the type and nature of the physical work performed]. PMID- 2591682 TI - Modeling in biomedical research: an assessment of current and potential approaches. Applications to studies in cardiovascular/pulmonary function and diabetes. PMID- 2591683 TI - [Idiopathic portal hypertension]. PMID- 2591684 TI - [Functional study, in man, of congestive gastropathy in cirrhosis by measurement of potential difference]. AB - The morphologic features of the gastric mucosa in patients with cirrhosis have been well investigated. The aim of this study was to evaluate its functional disruption by measuring the gastric potential difference. Forty patients were investigated, 12 control subjects and 28 consecutive cirrhotic patients with endoscopically proved congestive gastropathy. Potential difference was measured the morning, on an empty stomach, at least 3 days after endoscopy; the method used a double channel gastric perfused probe placed under fluoroscopy 10 cm above the cardia, and a subcutaneous reference, both connected to a millivoltimeter via gelose agar-KCl bridges. Potential difference was recorded in each case 20 min before (baseline) and after local instillation of lysine acetylsalicylate (500 mg) as a provocative test. Cirrhotic patients had significantly lower basal potential difference than controls (-28.3 +/- 1.5 mV vs -33.8 +/- 1.3mV, p = 0.007). Potential difference was significantly lower in patients with severe gastropathy than in patients with mild gastropathy (-20.5 +/- 2.1 and -28.9 +/- 1.6 mV, respectively, p less than 0.01). After stimulation with acetylsalicylate, the area under curve and the irritability index were greater in patients with gastropathy (81.4 +/- 12.8 vs 41.2 +/- 8.6 mV.min, p = 0.032 and 0.935 +/- 0.19 vs 0.290 +/- 0.07 mV.mV.min, p = 0.022, respectively). These differences were explained by a higher drop in potential difference (delta DPmax/baseline; 28.1 +/ 3 vs 16.1 +/- 3 p. 100, p = 0.006) whereas basal return time remained unchanged (16.2 +/- 2.1 vs 13.7 +/- 2.2 min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591685 TI - [Effect of chronic administration of cyclosporin A on choleresis in rats]. AB - The effect of therapeutic doses of cyclosporine A (CyA) on bile flow and bile salt output was studied in the rat. Thirty male Sprague-Dawley rats (250 to 380 g) were injected intraperitoneally with CyA (n = 15) or vehicle (n = 15) at the dose of 10 mg.kg-1 for 3 weeks. The effect of CyA on basal and taurocholate induced bile flow, on basal bile salt output and bile salt output under taurocholate infusion, and the effect of chronic administration of CyA on bile salt-independent bile flow was evaluated. Administration of CyA was associated with a decrease in basal bile flow (5.6 +/- 0.7 vs 6.7 +/- 0.7 microliters.min 1.100 g-1; p less than 0.001) and bile flow under taurocholate infusion (8.0 +/- 0.8 vs 10.9 +/- 1.1 microliters.min-1.100 g-1; p less than 0.001). Basal bile salt output (133.9 +/- 48.2 vs 173.8 +/- 53.6 nmol.min-1.100 g-1; p less than 0.003) and bile salt output under the infusion of taurocholate were significantly lower in cyclosporine-treated rats than in controls (443.3 +/- 48.2 vs 617.2 +/- 172.7 nmol.min-1.100 g-1; p less than 0.001). There was no significant difference in bile salt-independent bile flow between the 2 groups. There was no modification of seric alanine aminotransferase activity or hepatic histology. This study confirms that chronic administration of CyA at therapeutic doses can induce cholestasis. Cholestasis is related mainly to a decrease in bile salt secretion and bile salt-dependent flow. PMID- 2591686 TI - [Gastroenterology and chronobiology]. PMID- 2591687 TI - [Tri-annual rhythm of basal acid secretion and secretion stimulated by pentagastrin in duodenal ulcer]. AB - Duodenal ulcer is a recurrent disease with seasonal periodicity for pain and complications such as hemorrhage and perforation. Ulcer craters or symptoms seem to occur preferentially in early spring and autumn. Since acid secretion is one of the pathogenetic factors of the disease, we analyzed retrospectively basal and maximal (pentagastrin) acid secretion data obtained in 341 consecutive patients according to the month in which they were obtained. The patients were classified according to the activity of their ulcer (active, non active) and to the level of the peak acid secretion (hypersecretors, normosecretors). Basal acid concentration and output, and peak acid output were, both overall and month by month, higher in patients with active duodenal ulcer disease than in those who were non active, and in hypersecretors than in normosecretors. For all 341 patients as well as for normosecretors and non active ulcer patients, a triannual rhythm was detected for stimulated acid concentration and peak acid output. The highest values were noted in February, June, and October (period: 4 months). The amplitude of these rhythms was 3 to 4 percent, with differences between highest and lowest values of 30.4 mmol/l for concentration and 17.1 mmol/h for peak acid output. These rhythms for acid secretion during the year may contribute to the periodicity of duodenal ulcer events and should be analyzed in association with other factors which could be implied in ulcerogenesis. Moreover, this seasonal periodicity of acid secretion in duodenal ulcer should be taken into account in all therapeutic trials in which acid secretion is analyzed. PMID- 2591688 TI - Non-cholinergic neural excitation of the human rectum induced by acetorphan, an inhibitor of enkephalinase. AB - We have studied the effects of acetorphan, an inhibitor of enkephalinase, on the electrical activity of human rectum. Acetorphan activated the rectum of healthy volunteers by inducing bursts of spike potentials, this activation might become cyclical. In contrast, this drug failed to modify the motility of the aganglionic portion of the rectum in one case of Hirschsprung's disease, indicating that the effect of acetorphan involves the intramural plexuses. Activation of the rectum persisted in spite of the blockade of the cholinergic excitatory pathways by atropine, which confirms the existence of an excitatory non-cholinergic mechanism for the rectum. Our results also suggest that the neurotransmitter responsible for this effect is continuously released by the nervous structures implicated in the control of rectal motility. Immunohistochemical data show that the rectum is supplied by a rich enkephalinergic innervation. PMID- 2591689 TI - [Acute diarrhea in adults in a Parisian district. Clinical, bacteriologic endoscopic and histologic aspects. Study of 52 cases]. AB - From 1985 through 1988, 52 patients aged 16 to 85 years and referred for acute diarrhea underwent routine clinical, microbiological, endoscopic and histopathological examinations. Enteropathogens were isolated in 50 percent of patients, mostly from stool samples rather than from biopsy samples, though results were sometimes dissociated. Significantly lower digestive endoscopic abnormalities were seen in 60 percent of patients. Upper gastrointestinal endoscopy was not contributive. Rectal and colonic biopsies showed histological abnormalities in nearly all cases half of which were polymorphonuclear infiltrates and crypt abscesses. Glandular distortion was not found. An analysis of clinical, endoscopic and histological data showed that major abnormalities were mostly, but not constantly, related to infections due to enteroinvasive bacteria. As in other studies, a high rate of negative stool cultures was observed. Based on these results, we suggest to perform either further and more sophisticated microbiological investigations, or to conduct a routine search for viral infections whose incidence, among adult patients with acute diarrhea, is actually unknown. PMID- 2591690 TI - [Collagen colitis. Reflections apropos of 40 patients]. AB - The aim of this study was to evaluate the frequency of a thickened subepithelial collagen band in the colon, its relationship to diarrhea, and the clinical relevance of its detection. During a 3.5 year period (May 1985-January 1989), a total of 3,323 biopsy specimens were obtained during 6,254 colonoscopies. A subepithelial collagen thickening greater than 10 microns was found in 40 patients (1.5 percent of the patients). Further assessment of these 40 patients showed that this histological lesion was characterized by a frequent association with chronic diarrhea (in 36 patients, i.e. 90 percent) whatever the cause, with diseases such as diabetes mellitus (8 cases) or inflammatory arthropathies (6 cases) and with a microscopic colitis in all cases. Course of collagen thickening was variable and independent of clinical course. Diarrhea was a constant finding when the collagen thickening was greater than 15 microns and frequently improved (12 patients/14) during treatment with Collagenan. This study suggests that a subepithelial thickened collagen band is an uncommon change in the colon and is frequently associated with chronic diarrhea. The significance of this morphological change is unknown, and its contribution to the pathogenesis of the diarrhea remains questionable. PMID- 2591692 TI - [Pericarditis and colectasia disclosing Crohn's disease]. PMID- 2591691 TI - Glutamine transport in isolated rabbit ileal epithelium. AB - Oral rehydration therapy of diarrhea is based upon the promoting effect of glucose on sodium absorption. This ionic transport could be further enhanced by the addition of glutamine, an amino acid which is also the major energy source for the enterocyte. The aim of this in vitro study was to assess glutamine intestinal transport and to evaluate ionic movements associated with this transport. Strips of ileal epithelium from rabbits at weaning were mounted in Ussing chambers. Both sides of the epithelium were bathed with Ringer solution supplemented, after a basal period, with 2, 5, 10 or 25 mM glutamine. Unidirectional transepithelial fluxes of glutamine were measured with 3H and 14C tracers. Short circuit current, reflecting ionic transport, and potential difference were continuously monitored. Glucose 9 mM was later added to both sides. An apparent bidirectionnal transepithelial transport of glutamine was observed. The net result was a dose-dependent absorption (1.8 +/- 0.3 mumoles/h. cm2 at 25 mM). Glutamine induced a significant (p less than 0.01) dose-dependent saturable increase of short-circuit current and potential difference; the epithelial conductance was not modified. The addition of glucose did not significantly modify glutamine transport but caused and additional increase of short-circuit current. These results suggest that glutamine is actively transported by the ileal epithelium and stimulates ionic transport, suggesting Na+ absorption. The mechanism of this stimulation may differ from that of glucose, as the effects were additive. The present data provide support to the clinical evaluation of glutamine-supplemented rehydration solutions in the treatment of diarrhea. PMID- 2591693 TI - [An uncommon occlusive syndrome]. PMID- 2591694 TI - [Colonic cancer disclosed by eosinophil pneumopathy]. PMID- 2591695 TI - [Splenic artery aneurysm. Treatment using interventional radiology]. PMID- 2591696 TI - [Morphological study of the heart of Electrophorus electricus]. AB - Hearts of 7 Electrophorus electricus have been investigated on macroscopical and microscopical levels. Generally, the structure of the heart exhibits relative similarities with the other studied teleosts. The ventricular myocardium is mainly spongy and suggests that these structural features can offer an additional contraction power. PMID- 2591697 TI - [The morphological study of the respiratory organ of Electrophorus electricus]. AB - The respiratory organ of Electrophorus electricus is located in the oral cavity and is formed by papillar structures. The papilla consists basically of a cartilaginous central nucleus and is bounded by a connective layer. The results reveal structural adaptations for the respiration among fishes which have efficient respiratory circulation related with the venous blood. PMID- 2591698 TI - Functional morphology of the jaw muscles of two species of imperial pigeons, Ducula aenea nicobarica and Ducula badia insignis. AB - 1. The functional morphological study of the jaw muscles of 2 species of Imperial Pigeons, Ducula aenea nicobarica and Ducula badia insignis has revealed that the structural variations of the bill, osteological and connective tissue elements, and muscles of the jaw apparatus may be correlated to functional diversity in the fruit-eating adaptation of these birds. 2. Both the species of Ducula possess moderately long, thick and stout bill with flexion zones inside, elongated orbital process of the quadrate, stout pterygoid, broad palatine and wide mandibular ramus on either side with increased retroarticular space. Such skeletal modifications together with increased orbital space indicate wide attachment-sites for the muscles, aponeuroses, tendons, and ligaments. 3. The morphology of the quadrato-mandibular joints suggests possible 'coupled kinesis' of the upper jaw, along with depression of the lower jaw. However, in a rhynchokinetic upper jaw as possessed by these birds, the kinesis is just moderate. Hence the gape of the mouth is mainly effected by the depression of the lower jaw, rather less so by the protraction of the upper jaw. 4. Among the functional groups of muscles, M. depressor mandibulae, M. adductor mandibulae externus, M. pseudotemporalis profundus, and M. pterygoideus are especially well developed. The various components of these muscles are provided with stiff as well as wide aponeuroses and tendons (much stronger than those observed in Columba), indicating forceful opening and closure of the beaks for plucking off the fruit, grasping it hard and manipulating it with the help of the beaks before swallowing. 5. The fleshy insertion of the outer slip of M. pseudotemporalis profundus extends ventrally over the dorsolateral surface of the mandible much more than it does in Columba. Further, 2 short and stiff aponeuroses at the rostral insertion of the inner slip of the muscle increase the force of adduction on the mandible. 6. M. adductor mandibulae posterior has not only wider origin and insertion, but also greater mass of fibres than that observed in Columba. 7. M. adductor mandibulae externus and M. pterygoideus form muscle-complexes with the predominance of bipinnate and multipinnate arrangements of fibres and with occasional joining fibres between their components. Such arrangements of fibres indicate sustained force-production, rather than faster movements of the jaw apparatus. 8. M. pterygoideus ventralis lateralis has a well developed 'venter externus' slip which has its thick and fleshy insertion on the outer lateral angular and articular mandible.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2591699 TI - A histoenzymological investigation of the caudal neurosecretory system in six species of freshwater teleosts: a comparative study. AB - Enzymecytochemical features of the caudal neurosecretory system of 6 species of freshwater teleosts, Gudusia chapra, Gonialosa manmina (Clupeidae, Clupeiformes), Oxygaster bacaila (Cyprinidae, Cypriniformes), Mystus bleekeri (Bagridae, Cypriniformes), Sciaena coiter (Scienidae, Perciformes), and Mastacembelus pancalus (Mastacembelidae, Mastacembeliformes) have been investigated with the help of several specific histochemical techniques. No sex-dependent variation have been observed in the enzymecytochemical characteristics of the caudal neurosecretory system of the present species. The Dahlgren cells show intense RNA activity. Caudal neurosecretion lacks carbohydrate but seems to possess small amount of lipid. Acid-phosphatase is located in the Dahlgren cells and axons. Alkaline-phosphatase has been observed in the Dahlgren cells, axons, and urophysial blood-capillaries. Acetylcholine esterase is present in the Dahlgren cells, axons, and urophysis of Mystus, Mastacembelus, and Gonialosa, but lacking in the other 3 species. It is concluded that the caudal neurosecretory system of Mystus, Mastacembelus, and Gopialosa is innervated by cholinergic neurons. Despite their different taxonomic positions, caudal neurosecretory system of all 6 species produce similar responses to various enzymecytochemical tests, except for acetylcholine esterase. PMID- 2591700 TI - Responses induced by long-term toxic effects of heavy metals on fish tissues concerned with digestion, absorption, and excretion. AB - The present study relates to the bioassay as well as the responsiveness induced by long-term exposure to sublethal concentrations of soft acceptor heavy metals, lead (Pb, IV A) and cadmium (Cd, II B), in various fish tissues viz., stomach/intestinal bulb, intestine, liver, pancreas, and kidney of Mystus vittatus (Bloch) and Labeo rohita (Hamilton) belonging to 2 different trophic strata. Responses, however, have been recorded by histopathological and histochemical studies on the aforesaid tissues concerned mainly with digestion, absorption, and excretion. Histopathological observations depict the vacuolation, degranulation, exocytosis of the various cells including their nuclear damage. Erosion of the top plate of intestinal villi, enlargement of epithelial cells, shrinkage of glomeruli, destruction or disruption of the nephric tubular cells, etc. have also been registered. Histochemical investigations emphasize on the change in the intensity of staining reactions of biologically active macromolecules particularly amino acids of the protein component and glycogen among the carbohydrate component as well as acid, neutral and/or mixed mucopolysaccharides of the cells concerned. Toxic effects of the afore-mentioned heavy metals at the tissue level have been discussed. PMID- 2591701 TI - Digoxin-stimulated calcium transport across rat diaphragm interactions with aminophylline and verapamil. AB - 1. The effect of digoxin on calcium transport across muscle strips isolated from rat diaphragms was investigated. 2. Digoxin at concentrations ranging between 0.2 5.0 ng/ml in the incubation solution increased significantly (P less than 0.5) intracellular calcium in the diaphragm muscle strips in a dose-dependent pattern. 3. The inclusion of digoxin (2 ng/ml) and aminophylline (18.75 micrograms/ml) in the incubation medium showed a significant increase (P less than 0.001) in calcium uptake suggesting a synergistic effect on intracellular calcium accumulation. 4. The presence of digoxin with verapamil in the incubation medium showed a partial alleviation of the inhibitory effect of verapamil on calcium transport. 5. The effect of increasing calcium concentration in the presence of digoxin and digoxin plus aminophylline in the incubation medium, showed a nonsaturable linear relationship between calcium concentration and intracellular calcium accumulation. PMID- 2591702 TI - Effect of the inhibition of dopamine uptake on the dopamine- and dimethyldopamine induced-inhibition of the potassium-evoked release of [3H]acetylcholine from striatal slices. AB - 1. Dimethyldopamine was eight times more potent than dopamine in activating the D2 receptor that inhibits the potassium-evoked release of [3H]acetylcholine from striatal slices. 2. Cocaine and mazindol produced an eight-fold shift in the concentration-response curve for dopamine, but not for dimethyldopamine. 3. The IC50 of dimethyldopamine for the inhibition of [3H]dopamine uptake was thirty times greater than that for dopamine. 4. Dopamine may be less potent than dimethyldopamine at the D2 receptor because dopamine has a higher affinity for the dopamine uptake system, resulting in its rapid removal from the vicinity of the receptor. PMID- 2591703 TI - The effect of diaminopyridines on the activity recorded in the dorsal roots of isolated spinal cord. AB - 1. The diaminopyridines (DAP) increase the activity recorded in the dorsal roots of an isolated hamster spinal cord preparation. 2. The threshold for 3,4 DAP was 3 x 10(-6) M and the maximum effect was 10(-4) M. The threshold for 2,3 DAP was 3 x 10(-4) M and the maximum effect was at 10(-3) M. The threshold for 2,6 DAP was 10(-4) M and its maximum effect was at 3 x 10(-2) M. 3. When compared with the monoamino pyridines (AP) 4 AP was the most effective and the order of potency was 4 AP greater than 3,4 DAP greater than 2,3 DAP greater than 2 AP = 3 AP greater than 2,6 DAP. 4. Treatment with AP increased the activity simultaneously recorded in the dorsal and ventral roots, but whilst that in the dorsal root continued after washing away the amino pyridine, that in the ventral root ceased for a period of time. 5. There are indications that the amino pyridines may differently affect dorsal and ventral interneurones. PMID- 2591704 TI - Increase of muscarinic cholinergic receptors in the rat submandibular glands after parasympathectomy and repeated administration of haloperidol. AB - 1. The mechanisms of the supersensitivity to cholinergic drugs after chronic haloperidol was studied in normal and parasympathectomized submandibular glands of the rats. 2. Both parasympathectomy and haloperidol treatment for 7 days (2 mg/kg/day, i.p.) increased the sialogogue response of the glands to methacholine, a cholinomimetic drug. 3. Both denervation and haloperidol administration induce up-regulation of the muscarinic receptors as expressed per gram of the tissue. 4. Haloperidol causes no further increase in sensitivity than denervation alone. 5. These data demonstrate that secretory supersensitivity to cholinergic drugs in the rat submandibular glands, after chronic haloperidol and parasympathectomy is related to an increase in muscarinic cholinergic receptors. PMID- 2591706 TI - Lymphatic transport of salicylates in dogs. AB - 1. Pharmacokinetic parameters were determined for acetylsalicylic acid (ASA) and salicylic acid (SA) in plasma and lymph following the intravenous or oral administration of a water-soluble preparation of lysine-acetylsalicylic acid to dogs. 2. By both routes of administration, ASA but not SA, tended to be deposited in lymph, as indicated by the ratio between the area under the concentration-time curve constructed for the parent compound and its metabolite in lymph and plasma. 3. A reduced conversion of ASA to SA by esterases in lymph, and lymphatic absorption of ASA following the oral administration might be factors responsible for the accumulation of the compound in the lymphatic system. 4. It is suggested that the lymphatic system might serve as a temporary reservoir compartment for ASA. PMID- 2591705 TI - Some pharmacological properties of a new antitumor drug, CPT-11, in isolated muscle preparations. AB - 1. Pharmacological properties of a new antitumor drug, CPT-11, were studied in some muscle preparations. 2. CPT-11 induced contraction of guinea-pig ileal and tracheal preparations, which was blocked by atropine (10(-6) M). 3. CPT-11 potentiated the contractile responses of guinea-pig ileum to acetylcholine, nicotine, serotonin and BaCl2. 4. The chronic and inotropic effects induced by isoprenaline were depressed by CPT-11. 5. These results suggest that CPT-11 has an acetylcholine action. PMID- 2591707 TI - Differential electrophysiological effects of amiodarone on ventricular muscle and Purkinje fibers in canine one-day-old myocardial infarction. AB - 1. We examined the electrophysiological effects of acute exposure to amiodarone (AM) on ischemic myocardium. 2. Regional myocardial ischemia was performed by occlusion on left anterior descending coronary artery in dog heart. 3. Conventional glass microelectrode techniques were used for electrophysiological investigation of regional ischemia. 4. The effects of AM on action potentials of subendocardial Purkinje fibers and ventricular muscle excised from ischemic area were studied and compared the findings with those obtained from non-ischemic area. 5. Acute exposure to AM, 4.4 x 10(-5) M, prolonged the total duration of action potential in the ischemic ventricular muscle and decreased the maximum upstroke velocity of action potentials significantly. 6. On the other hand, in the ischemic Purkinje fibers, AM produced no significant actions. 7. These findings suggest that AM's antiarrhythmic activity is, at least in part, due to its differential effects on repolarization of ischemic Purkinje fibers and ventricular muscle. PMID- 2591708 TI - Tetrodotoxin-sensitive component in action potential plateau of guinea pig Purkinje fibers: comparison with the papillary muscle. AB - 1. The effects of tetrodotoxin on action potentials of isolated guinea pig purkinje fibers were examined and compared the findings with those obtained in the ventricular papillary muscle, by use of conventional microelectrode techniques. 2. Tetrodotoxin (5 x 10(-7)-10(-5) M) decreased the amplitude, overshoot, and maximum upstroke velocity of action potentials of the Purkinje fibers, and shortened the duration of action potential at all levels of repolarization concentration- and stimulus cycle length-dependently. 3. The longer the stimulus cycle length, the greater the shortening by the drug of the action potential duration. 4. In particular, the plateau potential of the Purkinje fibers exposed to tetrodotoxin was remarkably depressed, and which occurred even in case of blockade of K+ conductance, using tetraethylammonium. 5. On the other hand, a high concentration (10(-5) M) of tetrodotoxin did not significantly affect the papillary muscle action potentials. 6. These findings suggest that there is a tetrodotoxin-sensitive component of Na+ current in plateau voltage range of the Purkinje fibers, but little in the papillary muscle, and that the component plays an important role to maintain the plateau of Purkinje fibers action potential. PMID- 2591709 TI - Effect of extracellular calcium and calcium channel antagonists on ATP and field stimulation induced contractions of the mouse urinary bladder. AB - 1. The dependence on extracellular calcium of the response to the electrical stimulation, ATP and high K induced contractions has been studied in the mouse urinary bladder. 2. The responses to ATP, field stimulation and K induced depolarization were eliminated in calcium free EGTA medium. However, a small remanent of these responses was observed in the absence of calcium in the superfusing medium. 3. The calcium antagonists verapamil, nifedipine and diltiazem decreased in a dose dependent manner the contractions induced by ATP and electrical stimulation of the mouse urinary bladder. 4. The responses of the mouse urinary bladder to high K concentration were antagonized by verapamil and diltiazem, but nifedipine was less effective in decreasing the tonic component of the contraction induced by K in the muscle. 5. The responses of the mouse urinary bladder to electrical stimulation, ATP and high concentration of K are mainly dependent on the extracellular calcium. PMID- 2591710 TI - Dose effects of adenine on myocardial ATP content in the post-anoxic nonworking rat heart. AB - 1. Tissue ATP levels were measured in Langendorff perfused nonworking rat hearts subjected to 50 min anoxia prior to reperfusion with Krebs-Ringer bicarbonate (KRB) buffer alone or supplemented with 50 microM or 1 mM adenine for 60 min. 2. ATP content was restored to the normoxic range in hearts reperfused with 50 microM adenine in KRB (20.82 +/- SEM 1.90 mumol/g dry weight vs 24.95 +/- 0.83 in normoxic hearts, P = NS). 3. Reperfusion with oxygenated KRB alone or buffer with 1 mM adenine failed to improve ATP levels (17.23 +/- 0.91 mumol/g dry weight for buffer alone, 15.60 +/- 0.46 with 1 mM adenine and 13.45 +/- 0.93 for anoxic hearts not reperfused). 4. These findings indicate that adenine at 50 microM dosage can restore ATP concentrations to the normoxic range after 60 in of anoxia in the nonworking rat heart while raising the adenine dose to 1 mM inhibited the tissue ATP content. PMID- 2591711 TI - Effect of nomifensine on platelet monoamine oxidase activity in chronic schizophrenic patients. AB - 1. The levels of platelet MAO activity increase and the frequency of affective symptoms diminish in the depressed chronic schizophrenics treated with nomifensine. 2. Nomifensine has no inhibitory effect in vitro on platelet MAO activity in depressed schizophrenic pellets. PMID- 2591712 TI - Josamycin concentrations in human dental granuloma after a single oral administration of josamycin. AB - 1. Josamycin concentrations in human serum and dental granuloma after a single oral administration of josamycin (600 mg) were assayed by an agar diffusion (paper disc) method. 2. The mean peak josamycin concentrations in serum and dental granuloma occurred at an identical time, approximately 90 min, and were 0.88 micrograms/ml and 1.61 micrograms/g, respectively. 3. The mean concentration ratio of dental granuloma to serum at the peak time was 2.24. 4. Josamycin concentration in dental granuloma at the peak time exceeded MIC80 for clinically isolated strains of Streptococcus group A, Peptostreptococcus spp., and Bacteroides spp. PMID- 2591713 TI - Purinergic modulation in the flounder gut. AB - 1. Spontaneous mechanical responses of ileum and rectum of the flounder were recorded isometrically. 2. Both ileal and rectal segments showed positive dose dependent inotropic but not chronotropic responses to ATP. 3. The P2 receptor antagonist alpha-beta-M-ATP induced contractures in flounder ileum and rectum. Pretreatment with this agent blocked the responses of both ileum and rectum to ATP. 4. Adenosine abolished rhythmic activity and lowered basal tonus in the ileum but in the rectum adenosine induced dose-dependent positive inotropic responses. 5. Theophylline pretreatment abolished the positive inotropic effects of adenosine in the rectum and it prevented the inhibitory actions of adenosine in the ileum. 6. It is concluded that the positive actions of ATP in ileum and rectum are mediated via P2 purinoreceptors. The positive response of the rectum and inhibition of the ileum seen with adenosine appear to be mediated via mixed populations of excitatory and inhibitory P1 purinoreceptors. PMID- 2591715 TI - Effect of pinealectomy on annual testicular cycle of Indian chequered water snake, Natrix piscator. AB - Pinealectomy for 60 days (noted every month of the year), in the tropical Indian chequered water snake. Natrix piscator, caused inhibition of testicular growth during late progressive and active phases and retarded the rate of regression during regressive phase; during sexually inactive phase the testes remain partially active. The weight of the accessory sex organs, vas deferens, and kidney (along with the renal sex segment activity) followed the same pattern as that of the testes. Thus, it may be concluded that the pineal gland of this ophidian participates in the regulation of seasonal testicular cycle, probably via the hypothalamo-hypophyseal axis, and hence the effects of pinealectomy are seasonal and a reproductive phase-dependent phenomenon. PMID- 2591714 TI - Is the pineal involved in the stimulatory influence of prolactin on tail regeneration in lizards? Studies with exogenous prolactin in lizards exposed to continuous darkness. AB - We have recently demonstrated that continuous light stimulates tail regeneration in the gekkonid lizard, Hemidactylus flaviviridis, whereas continuous darkness and pinealectomy depress regeneration. As a sequel to this observation, the effect of exogenous ovine prolactin (oPRL) on tail regeneration in normal (NL) and pinealectomized (PX) Hemidactylus exposed to continuous darkness (L:D 0:24) during the monsoon season was investigated. Once-daily intraperitoneal (ip) injections of 500 micrograms/kg oPRL were administered to a group of NL lizards, a group of PX lizards, and a group of sham-PX (sPX) lizards, 5 days prior to tail autotomy and 50 days afterward. Three groups--PX, sPX, and NL animals--served as the controls and received once-daily ip injections of 0.6% saline. Our observations show that initiation of regeneration, daily growth rate, total length of new growth (regenerate) at the end of regeneration, and total percentage replacement of lost (autotomized) tail were all significantly enhanced in oPRL-treated NL lizards as compared with their saline-treated (NL, PX, and sPX) and oPRL-treated (PX and sPX) counterparts. It is suggested that PRL may be the active factor that speeds up the rate of tail regeneration in lacertilians. The role of the pineal organ in vertebrate photoreception and the possibility that in Hemidactylus the presence of an intact pineal is somehow linked with the favorable influence of PRL on tail regeneration are discussed. PMID- 2591716 TI - Change of steroidogenic pathways in the ovary of a tropical catfish, Clarias macrocephalus, Gunther, after hCG treatment. AB - Adult female catfish received an im injection of 454 IU hCG in 0.2 ml saline. Sixteen hours later, the ovarian tissue from the hCG-treated or control fish was aerobically incubated in vitro with 4-[14C]progesterone or 17 alpha hydroxyprogesterone at 30 degrees for 60 min. When progesterone was employed as the substrate, significant production of androstenedione and testosterone was observed in the control group. However, after the hCG injection, a markedly higher amount of 20 beta-hydroxy-4-pregnen-3-one was produced. Furthermore, the androgen production was diminished, and the production of 5 beta-reduced C21 metabolites such as 5 beta-pregnane-3,20-dione and 3 alpha-hydroxy-5 beta-pregnan 20-one was also reduced in the hCG-treated group. From 17 alpha hydroxyprogesterone as a substrate, considerable amounts of androstenedione and testosterone were obtained as the metabolites in the control group. However, after the hCG treatment, production of 17 alpha, 20 beta-dihydroxy-4-pregnen-3 one (17 alpha, 20 beta-diOHprog) and its 5 beta-reduced metabolite was markedly stimulated, while the androgen production was reduced drastically. By evaluating the yield of each product, it was suggested that the tentatively calculated activity of 17 alpha-hydroxylase and C-17-C-20 lyase was diminished by the hCG treatment and that 20 beta-hydroxysteroid dehydrogenase was activated. It indicates that hCG changed the ovarian steroidogenic pathway from androgen production to formation of 17 alpha, 20 beta-diOHprog, an inducer of germinal vesicle breakdown. PMID- 2591717 TI - Steroidogenesis in Fundulus heteroclitus. II. Production of 17 alpha-hydroxy-20 beta-dihydroprogesterone, testosterone, and 17 beta-estradiol by various components of the ovarian follicle. AB - Fundulus heteroclitus prematurational follicles (1.3-1.4 mm) were dissected into various components and cultured in vitro to examine the type of cells involved in the synthesis of steroids upon F. heteroclitus pituitary extract (FPE) stimulation or addition of exogenous precursors (25-hydroxycholesterol or pregnenolone). Culture media and follicular tissue extracts were assayed for 17 alpha-hydroxy-20 beta-dihydroprogesterone (17 alpha-OH.20 beta-DHP), testosterone (T), and 17 beta-estradiol (E2) content using specific radioimmunoassays. Complete removal of the follicle wall (denuded oocytes) eliminated steroid accumulation induced by FPE treatment. Removal of the theca/epithelium layer (defolliculated oocytes) did not affect the steroidogenic response (17 alpha OH,20 beta-DHP, T, E2 production) of the follicles to FPE or exogeneously added precursors (25-hydroxycholesterol or pregnenolone). Isolated theca/epithelium layers secreted only T. Isolated follicular preparations that did not contain the oocyte (theca/epithelium layers or follicle cells) secreted higher levels of steroids to the culture media than did intact follicles. We conclude from these results that (1) the follicle cells (granulosa cells) are the primary source of the various steroids produced by the F. heteroclitus ovarian follicle in response to FPE stimulation: (2) the synthesis of 17 alpha-OH,20 beta-DHP and E2 does not require the involvement of two cell types as shown in other teleosts; (3) the theca/epithelium layer is able to produce T but lacks the aromatase activity necessary for E2 synthesis; and (4) steroids synthesized in the follicle wall are both secreted to the medium and accumulated in the oocyte. PMID- 2591718 TI - Effect of estrogen on calcium homeostasis and pituitary hormones in the growing chick. AB - An experiment was carried out to investigate the effect of a range of estradiol (E2) doses (0.1-6.5 micrograms/g body wt/day) on vitamin D metabolism and the plasma levels of growth hormone (GH) and prolactin (PRL) in the growing chick. Doses of 0.5-0.7 microgram/g E2, which are insufficient to raise the plasma calcium level, did induce an increase in growth rate, an increase in 25 hydroxyvitamin D 1 alpha-hydroxylase (1-hydroxylase) and 24-hydroxylase activities, and an increase in plasma GH level. These parameters leveled off or fell over the dose range 1-2 micrograms/g E2 but there was evidence of a second peak in 1-hydroxylase activity at 6 micrograms/g E2. At this high dose rate, the plasma Ca level rose to 8 mM, as it does in the laying hen; 24-hydroxylase activity, growth rate, and plasma GH and plasma PRL levels all decreased. It was concluded that the dose response to estrogen in the growing chick is not linear and, in the case of 1-hydroxylase activity, may even be biphasic. PMID- 2591719 TI - Steroidogenic role of the caudal neurosecretory system in the flounder, Platichthys flesus. AB - Transfer of flounders from seawater (SW) to fresh water (FW) resulted in a small reduction in circulating cortisol levels and urophysial protein storage. Transfer of flounders from FW to SW resulted in a larger increase in plasma cortisol and specific urophysial protein storage. Over the first 4 days after transfer from FW to SW there was a positive correlation between the observed changes in urophysial urotensin I (UI) content and plasma cortisol. This apparent steroidogenic effect of UI was supported by the increases in plasma cortisol observed following iv injection of crude flounder urophysial gland extract and synthetic Catostomus commersoni UI. The study supports a contribution of the caudal neurosecretory system to the control of interrenal steroidogenesis as part of the integrated osmoregulatory physiology of euryhaline species like the flounder. PMID- 2591720 TI - Vernal increases in prolactin levels of nonbreeding male and female canvasbacks (Aythya valisineria). AB - Serum levels of prolactin were determined in nonbreeding male and female canvasbacks (Aythya valisineria) from mid-April to late June to evaluate the temporal changes occurring during spring. During this time interval, serum prolactin levels increased 1.5- to 2-fold in both males and nonlaying females (P less than 0.01). Serum prolactin levels of males and females exposed to natural lighting and temperature at Delta, Manitoba (50 degrees 11'N, 98 degrees 19'W), steadily increased from mid-April when the daylength was 14 hr light and peaked in mid-June when daylength was 16.25 hr light. Administration of exogenous estradiol via slow-release subdermally implanted capsules in females with intact reproductive systems had a marginal effect on reducing the seasonal increase in prolactin. Exogenous testosterone in similar slow-release capsules implanted subdermally in males had no influence on circulating prolactin levels. PMID- 2591721 TI - The deleterious effects of cortisol implantation on reproductive function in two species of trout, Salmo trutta L. and Salmo gairdneri Richardson. AB - Implantation of a cortisol-releasing pellet (60 mg kg-1 fish) into the peritoneal cavity of brown trout, Salmo trutta L. (sexually maturing males and females), and rainbow trout, Salmo gairdneri Richardson (maturing males and immature fish of both sexes), significantly elevated their plasma cortisol level. At 18 days postimplantation, cortisol-implanted sexually maturing male brown trout had smaller gonads, a lower plasma testosterone level, and less gonadotropin in their pituitary gland than control fish. Plasma levels of 11-ketotestosterone and gonadotropin were not significantly affected. Cortisol-implanted sexually maturing female brown trout had smaller gonads, reduced plasma levels of 17 beta oestradiol, testosterone, and vitellogenin, and a lower pituitary gland gonadotropin content than control fish. The plasma gonadotropin level was unaffected. At 36 days post-implantation, cortisol treatment of maturing male rainbow trout significantly suppressed plasma gonadotropin levels. Plasma levels of testosterone, 11-ketotestosterone, and 17 alpha,20 beta-dihydroxy-4-pregnen-3 one, pituitary gonadotropin content, and gonad size were not significantly affected. In sexually immature female rainbow trout, cortisol administration suppressed the level of vitellogenin in the plasma, compared to control-implanted fish. The 17 beta-oestradiol level was not affected. Cortisol implantation did not affect the plasma testosterone level in sexually immature male trout. These results suggest that prolonged elevation of plasma cortisol, to levels well within physiological range, can affect a wide range of reproductive parameters in both brown and rainbow trout. Further, some effects are manifest in immature as well as in mature fish. These findings are discussed in relation to the effects of cortisol treatment on the state of health of the treated fish. PMID- 2591722 TI - Increases in calbindin D 28K mRNA in the uterus of the domestic fowl induced by sexual maturity and shell formation. AB - Uterine concentrations of calbindin D 28K mRNA were measured in immature pullets and laying hens by dot-blot hybridization using a [32P]cRNA probe prepared from the calbindin cDNA. In immature pullets, estrogen increased the calbindin mRNA level and the plasma concentration of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. When testosterone was administered with estrogen there was a further increase in calbindin and its mRNA and an increase in the free 1,25-(OH)2D3 index calculated as the ratio of the molar concentrations of total 1,25-(OH)2D3 and vitamin D binding protein (DBP). In laying hens the uterine concentration of calbindin mRNA was low 4 hr after ovulation, but increased most markedly 12 and 18 hr later, when shell calcification took place. Calbindin concentration remained unchanged during the different stages of egg formation but was much higher in laying hens than in pullets treated with sex steroids. Suppression of shell formation by premature expulsion of the egg decreased the concentrations of calbindin mRNA and uterine calbindin and the free 1,25-(OH)2D3 index in the plasma. A concomitant increase in calbindin and its mRNA was observed at resumption of shell formation in hens previously laying shell-less eggs. Withdrawal of food for 44 hr decreased the uterine concentration of calbindin and its mRNA without a change in the free 1,25-(OH)2D3 index in the blood. It is concluded that the synthesis of uterine calbindin is stimulated primarily at sexual maturity and at calcification of the first shell by transcriptional processes. The daily increase in calbindin mRNA associated with shell formation and the absence of a concomitant change in calbindin concentration suggest that post-transcriptional processes exist and that stimuli other than the sex steroid or the 1,25-(OH)2D3 are involved in regulation of calbindin synthesis in the uterus. PMID- 2591723 TI - Partial biochemical and biological characterization of purified chicken growth hormone (cGH). Isolation of cGH charge variants and evidence that cGH is phosphorylated. AB - Chicken growth hormone (cGH) was purified from frozen pituitary glands obtained from recently sacrificed broilers. Glands were homogenized in a protease inhibitor solution (0.5 mM PMSF, 50 KIU/ml aprotinin, pH 7.2); extract was taken to pH 9.0 with calcium hydroxide and the supernatant was differentially precipitated with 20% (fraction A) and 50% (fraction B) ammonium sulfate. cGH (fraction B-DE-1) was obtained in pure form from fraction B after DEAE-cellulose chromatography at pH 8.6, with a yield of 2.9 mg/g tissue. Three charge variants of cGH (Rf = 0.23, 0.30, and 0.35) could be isolated by electroelution after semipreparative nondenaturing polyacrylamide gel electrophoresis of fraction B-DE 1. These charge variants showed the same apparent molecular weight (26,300 Da) by sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions. Isoelectric focusing of fraction B-DE-1 revealed two major components (pI = 7.2 and 7.4) and four minor bands (pI = 6.2, 6.7, 7.1, and 7.5). It was found that fraction B-DE-1 contained a significant amount of esterified phosphate (1 nmol PO4/3.5 nmol protein) similar to that reported previously for ovine GH. The functional integrity of the cGH obtained here was characterized by two heterologous and one homologous bioassays. High activity was shown by fraction B DE-1 in the tibia assay (1.76 UI/mg) and in the liver ornithine decarboxylase assay (sixfold over control), both made in hypophysectomized rats; and it also stimulated lipolysis (138 and 215% at 10 and 100 ng/ml, respectively) on chicken abdominal adipose tissue explants. PMID- 2591725 TI - Central Asian cobra venom cytotoxins-induced aggregation, permeability and fusion of liposomes. AB - The processes of membrane aggregation, permeability and fusion induced by cytotoxins from Central Asian cobra venom were investigated by studying optical density of liposome samples, permeability of liposome membranes for ferricyanide anions and exchange of lipid material between the membranes of adjacent liposomes. Cytotoxins Vc5 and Vc1 were found to induce aggregation of PC + CL and PC + PS liposomes. Cytotoxin Vc5 increased also the permeability of the liposomes for K3[Fe(CN)6] and enhanced their fusion. Cytotoxin Vc1 increased membrane permeability and enhanced fusion of PC + CL samples only. The changes in membrane permeability and fusion were found to occur within a single value of cytotoxin concentrations. The fusogenic properties of the cytotoxins studied are supposed to be due to the ability to dehydrate membrane surface and to destabilize the lipid bilayer structure. Fusion probability is largely defined by the phospholipid composition of the membranes. A model of interaction of cytotoxins with cardiolipin-containing membranes is offered. PMID- 2591724 TI - High standard one-loop potential clamp device for Ranvier nodes. AB - Starting from the observation that using a conventional potential clamp device for membrane current measurements in Ranvier nodes neither the kinetics of sodium currents nor the constant field concept agree satisfactorily with the Hodgkin Huxley-Frankenhaeuser (HHF)-formalism, an extendend measuring system has been developed. The extensions introduced base largely on physical implications of myelinated nerve fibres which give rise 1. to systematic distortions of any current records at the high frequency end and 2. to current proportional deviations of the membrane potential from desired potential values. In addition, we provided to meet any unwanted current load during membrane current measurements and to push the time resolution of the measuring system to the highest possible value. After having tested thoroughly the new circuitry by appropriate physical methods, from sodium current measurements the following conclusions were drawn: 1. Occasional deviations of sodium current kinetics near the sodium equilibrium potential from the predictions of the HHF-formalism are measurement errors. 2. The constant field formalism holds for sodium currents in the potential range of biological relevance only. 3. Instantaneous sodium current measurements, however, are of unsatisfactory significance because for this kind of experiments the time resolution of the measuring system used might be still too low. PMID- 2591726 TI - Antibodies to DNAs chemically modified with osmium structural probes. AB - It has previously been shown that osmium tetroxide, pyridine (Os,py) and osmium tetroxide, 2,2'-bipyridine (Os,bipy) are powerful probes of the DNA structure. To increase the possibilities of the detection of osmium-modified DNAs polyclonal antibodies against DNA modified with Os,py and Os,bipy were elicited in rabbits. Specificity of these sera or purified IgG was tested by ELISA and retardation of the DNA electrophoretic mobility in agarose gels. Antibodies against DNA-Os,py (anti-DNA-Os,py) reacted with single-stranded and double-stranded DNA-Os,py but they did not react with unmodified DNA; with DNA-Os,bipy only a weak reaction was observed. The specificity of the anti-DNA-Os,bipy was similar. Competition experiments with anti-DNA-Os,py showed a weak reaction with RNA-Os,py but no reaction with osmium-modified proteins and unmodified proteins and RNA. The results suggest that anti-DNA-Os,py may become an important tool in studies of DNA structure in situ. PMID- 2591727 TI - The effect of ionic strength on the age dependent stability of rat erythrocyte membranes. PMID- 2591728 TI - Cardiovascular risk factors in a French Canadian population: resolution of genetic and familial environmental effects on blood pressure using twins, adoptees, and extensive information on environmental correlates. AB - Genetic and environmental influences on systolic (SBP), diastolic (DBP), and mean arterial (MBP) blood pressure were examined using an expanded version of a path model in which parents and their singleton, twin, and adopted offspring were incorporated, and which also included an environmental index as an estimate of the underlying familial environmental component. Estimates of genetic heritability are lower in parents (10-15%) than in offspring (40-50%). Cultural heritability was significant for SBP (0.31) and MBP (0.40), and an intergenerational effect was found for DBP, with higher estimates in parents (0.42) than in offspring (0.21). Marital resemblance was significant, and no support was found for differential maternal and paternal cultural transmission. Two novel results arising from this study are 1) gender-specific sibling effects, with greater female than male resemblance for SBP and MBP and the opposite pattern for DBP, and 2) the suggestion of extra twin resemblance arising on account of additional shared environments and resulting in greater like-sex than opposite-sex twin resemblance. The major conclusions drawn from this study are that 1) parameter estimates are stable with or without the use of extensive environmental indices, and 2) the addition of twins and adoptees did not significantly impact the results, with the exception of a possible influence of the adoptees in estimates of cultural heritability for DBP. Combining both these features (i.e., extended relatives and environmental indices) enables testing for additional sources of familial aggregation, which is not possible using the traditional nuclear family approach and results in a more accurate assessment of the relative roles of heredity and environment on blood pressure than has been previously possible. PMID- 2591729 TI - Importance of hereditary disease at a Neuropsychiatric Institute in Mexico City. AB - The objective of this study is to investigate the type, importance, and incidence of hereditary diseases in patients at the National Institute of Neurology and Neurosurgery in Mexico City. A review of 6,258 files indicated that hereditary diseases represent an important problem for the Institute. Of the diseases with the highest incidences, hereditary factors have an important role in seven (epilepsy, depression, facial palsy, schizophrenia, mental retardation, migraine, and Parkinson's disease). Diseases of known monogenic etiology represent 1.5% of all the cases. PMID- 2591730 TI - Equivalence of the mixed and regressive models for genetic analysis. I. Continuous traits. AB - The mixed model of segregation analysis specifies major gene effects and partitions the residual variance into polygenic and environmental components. The model explains familial correlations essentially in terms of genetic causation. The regressive model, on the other hand, is constructed by successively conditioning on ancestral phenotypes and major genes. Familial patterns of dependence are described in terms of correlations without necessarily introducing a particular scheme of causal relationship. These two approaches are compared both theoretically and numerically through computer simulations for the case of continuous traits on nuclear families. The class D regressive model, which is characterized by equal sib-sib correlations, is mathematically and numerically equivalent to the mixed model. The simpler class A regressive model, which is also characterized by equal sib-sib correlations determined in this case by the common parentage, provides good estimates of the mixed model parameters: major gene parameters and residual polygenic heritability, derived from the parent offspring correlation. However, in the absence of a major gene, the restriction imposed by the class A model on the sibling correlation can affect the conclusions of segregation analysis: False inference of a major gene was observed in two out of ten replicates. Our simulations also indicate that the mixed model allowing for different heritabilities in adults and children leads to correct estimates of the major gene parameters and residual familial correlations (parent offspring and sib-sib) as specified by the class A model. For all the models studied, major gene effects, when present, are correctly detected and estimated. PMID- 2591731 TI - Complex segregation analysis for a three-allele locus: experience from an analysis of acid phosphatase activity. AB - A complex segregation analysis of acid phosphatase activity in 50 British families showed that the essential features of the acid phosphatase polymorphism, i.e., a major gene with three alleles, is retrieved by using the biallelic mixed model. The estimates of gene frequency and displacement obtained from segregation analysis were in agreement with those obtained from electrophoretic studies. In addition, there was evidence for a multifactorial component. PMID- 2591732 TI - Test of genetic heterogeneity of cleft lip with or without cleft palate as related to race and severity. AB - The question of possible heterogeneity among population groups and phenotypic groups on the role of major gene in the etiology of cleft lip with or without cleft palate [CL(P)] was examined using the uniformly collected data in Hawaii. Complex segregation analysis was used to analyze patterns of family resemblance under the mixed model incorporating the effects of major gene and multifactorial inheritance. Analysis of the entire data showed superior fit of the mixed model including the effects of both major gene and multifactorial inheritance over the model of major gene alone or multifactorial inheritance alone. No significant heterogeneity could be detected between the high-incidence group (Oriental or Japanese) and the low-incidence group (non-Oriental) in the underlying general model, although higher heritability was observed in general. When families were classified into "severe" and "mild" phenotypes based on cleft lip vs. cleft lip and palate or unilateral vs. bilateral cleft in the proband, no significant differences could be detected between the two types in the underlying genetic model. PMID- 2591733 TI - Genetic studies on an Alzheimer clinic population. AB - All patients attending the Clinic for Alzheimer Disease and Related Disorders have detailed family histories taken by a geneticist. To date, genetic histories are available for 446 consecutive, unrelated individuals. Of these, 151 (33.9%) are diagnosed as having "probable" (N = 141) or "autopsy-confirmed" (N = 10) Alzheimer disease according to recognized criteria. This data base represents a relatively unselected population with respect to more than one person in the family having dementia. Seventy-one of these 151 index cases (47.0%) have a positive family history of dementia, of which 8 (5.3%) may represent the familial (autosomal dominant) form of Alzheimer disease (FAD). Age-corrected empiric recurrence risks for Alzheimer disease/dementia were calculated for first-degree relatives of these 151 index cases using the Kaplan-Meier lifetable method. PMID- 2591734 TI - The molecular-cytogenetic analysis of grasses and its application to studying relationships among species of the Triticeae. AB - An analysis of four species from the genus Secale, including the study of different accessions, has shown that the properties of DNA clones of monomer units from three repeated sequence loci, namely, Ter, Nor, and 5S DNA, proved to be representative of the entire loci from which they were isolated. This finding in Secale species, including the discovery of a new locus for 5S DNA on chromosome 5R, has been used to interpret information on the Ter, Nor, and 5S DNA loci from 15 species in the Triticeae complex. The evolutionary relationship among species suggested by the DNA sequence data has shown many consistencies with a number of other characters such as those used in classical systematics, as well as geographical distribution data and isozyme and chromosome-pairing studies. Apparent inconsistencies such as a close relationship between the R and P genomes at the Ter loci are interpreted in terms of amplification-deletion phenomena known to occur at repetitive sequence loci. In addition, this study included species endemic to Australia and thus provided a broad time span in which to consider some features of repeated sequence family evolution, such as the conservation of certain parts of 5S DNA spacer regions. PMID- 2591735 TI - Immunoglobulin molecular genetics: the prospects for mutational analysis of the chromosomal immunoglobulin genes. AB - Homologous recombination between transferred and chromosomal DNA can be used to effect precise, predetermined modifications of the chromosomal genes. Ultimately this phenomenon should allow the assessment of genetic regulatory elements as they function in the normal chromosomal environment. We have previously described a system for isolating mutant hybridoma cells that are defective in immunoglobulin (Ig) production, with a view toward using these mutants to define cis-acting elements that influence Ig gene expression. Here we describe results that indicate that homologous recombination between transferred and chromosomal Ig genes can be used to map Ig mutations by marker rescue. PMID- 2591736 TI - Intraspecific and interspecific genetic variation in Drosophila. AB - Utilizing the technique of DNA-DNA hybridization, we have characterized the degree of genetic variability in single-copy DNA both within and between several species of Drosophila. The results of intraspecific variation studies indicate considerable variation both for levels of nucleotide heterozygosity (estimated to be over 2%) as well as for insertions-deletions. Interspecific studies confirm this great deal of variability and further establish an extreme heterogeneity within Drosophila genomes for rates of divergence. This heterogeneity is much more extreme than that seen between exons and introns. The degree of single-copy DNA divergence generally supports phylogenetic affinities deduced from more traditional methods. However, exceptions occur where single-copy DNA divergence is not correlated with other properties such as degree of chromosomal differentiation, morphology, or ability to form interspecific hybrids. We argue that single-copy DNA divergence as measured by DNA-DNA hybridization is an accurate indicator of phylogenetic relationships and therefore sheds light on the evolution of other biological properties. Many, if not most, evolutionary tests require an accurate phylogeny of the group being studied and DNA, because of the high information content inherent within the molecule, offers the best hope of deriving true phylogenies. PMID- 2591737 TI - Nuclear power plants and natural populations of Mexican Drosophila. AB - With the worldwide proliferation of nuclear power plants has come the need to study the biological effects of the operation of the reactors on surrounding populations. We have begun a long-term study of the sibling species Drosophila melanogaster and D. simulans in the area of Laguna Verde in the state of Veracruz in Mexico. Laguna Verde, on the Gulf of Mexico about 75 km north of the city of Veracruz, is the location of the country's first nuclear power plant. This plant has not yet gone "on-line." The species have been collected from two sites, one of which is south of the reactor and is in the path of the prevailing north to south wind flow. The other collecting site is west of the plant. The species are being studied for the following: species frequency, desiccation resistance, vagility, proportion of larvae pupating, pupation height, and egg to adult survival after irradiation. To date we have noted both spatial and seasonal differences in a number of these characteristics. The information being gathered will serve as base-line data for monitoring the future operation of the nuclear power plant. PMID- 2591738 TI - Could natural selection account for molecular evolution and polymorphism? AB - A model of molecular evolution is presented that is based on the combined action of natural selection, genetic drift, and mutation. The mathematical description of the model uses strong-selection, weak-mutation limits to approximate the dynamics of multidimensional diffusion processes with one dimensional Markov chains. This approach leads to a great simplification of the dynamics and provides a unified method for describing many different mechanisms of natural selection. In this paper two models are examined, one based on selection in a randomly fluctuating environment, the other on overdominance. Both models exhibit similar dynamics, with a rapid buildup phase that introduces new alleles into the population, followed by a relatively quiescent phase where new alleles may enter and leave the population at a low rate. If occasional extreme environmental changes occur that favor particular alleles, the resulting dynamics turn out to be in remarkable agreement with many of the observations on molecular evolution and polymorphism. Thus the model is at least as successful as the neutral theory in accounting for evolutionary events at the molecular level. PMID- 2591739 TI - The human recombination strand exchange process. AB - A mechanism for the initiation of general recombination that involves the formation of left-handed Z-DNA heteroduplex segments adjacent to right-handed B DNA heteroduplex segments is discussed. The paranemic nature of this initiation structure allows for homology recognition in the absence of strand cleavage. This model suggests that proteins catalyzing recombination initiation via the formation of paranemic joint should in some capacity recognize Z-DNA. Other studies have shown that both the RecA protein of Escherichia coli and the Rec1 protein of Ustilago maydis have a greater affinity for Z-DNA than B-DNA. Here we have used Z-DNA affinity chromatography to purify a peptide of approximately 120 kilodaltons from a human tumor cell line that catalyzes a simple recombination strand-transfer reaction similar to one developed for the characterization of the RecA and Rec1 proteins. We report details of the characterization of the human strand-transfer activity and identified a potential human recombination complex. PMID- 2591740 TI - Blood biochemical polymorphisms as markers for genetic characteristics of wild Spanish and domestic rabbits. AB - Seventeen blood proteins were studied in a sample of 412 Spanish wild rabbits and in 598 domestic rabbits belonging to various breeds. The wild rabbit populations showed a high level of genetic polymorphism. Six loci were monomorphic, while the remaining ten loci were segregating for at least two alleles. Two of the loci that were polymorphic in the wild rabbits were monomorphic in the domestic ones. Wright's inbreeding coefficient in the total Spanish wild rabbit population was F = 5.66, indicating subdivision of the total population. Inbreeding coefficients, estimated by Kidd et al.'s method (Anim. Blood Grps, Biochem. Genet. 11: 21-38), differed significantly from zero, being 15.62%, in wild rabbits and 6-12% in domestic breeds, indicating consanguinity. Genetic distances between wild rabbit populations showed that factors other than geographic distance (e.g., bottlenecks, barriers such as rivers, mountains, etc.) may explain the result that a northern population forms a cluster with two central populations whereas the northeastern populations form a different cluster with another central population. Populations of the first cluster are more closely related to the captive populations than others. There are three population clusters of domestic rabbits, namely (1) New Zealand White and a hybrid combination; (2) Spanish Common, Butterfly, Burgundy, and Californian; and (3) Spanish Giant. PMID- 2591741 TI - Inheritance of cold shock tolerance in hybrids of Drosophila virilis and Drosophila lummei. AB - The genetic basis of the difference in cold shock tolerance between the southern temperate Drosophila virilis and its boreal relative D. lummei is studied. After adult eclosion, the parental stocks, reciprocal F1 and backcross hybrids were pretreated for eight days at 18 degrees C or at 6 degrees C. The cold shock used consisted of fast cooling to -10 degrees C and exposure to this temperature for varying lengths of time. D. lummei tolerated such exposure for 40-50% longer than did D. virilis (100-135% after acclimation). Reciprocal F1 females, differing only in their maternal cytoplasm deviated significantly from each other, and the reciprocal F1 males even more so, the contribution of the X chromosome being three to four times that of the cytoplasm. The cold resistance scores of the hybrid males were more extreme than those of the parental stocks. Autosomally heterozygous males with the X chromosome and cytoplasm of virilis were the weakest flies studied. The reciprocal males (X chromosome and cytoplasm of lummei) survived better than the parental lummei stock. The reciprocal differences decreased after cold temperature acclimation. The roles of the four major autosomes were analyzed by backcrossing the reciprocal F1 males with females of the virilis marker stock. The third chromosome of lummei as heterozygous contributed most to cold tolerance, while the other autosomes had a rather weak effect in the opposite direction (virilis homozygotes survived better), which disappeared after acclimation at 6 degrees C. Some of the cold susceptibility of F1 hybrids disappeared in chromosomally identical backcross flies, indicating complex cytoplasm-chromosomal interactions. PMID- 2591742 TI - Cloning and analysis of a human 86-kDa heat-shock-protein-encoding gene. AB - An 86-kDa heat-shock-protein-encoding (hsp86) cDNA probe permitted to identify, in whole genomic human DNA, two EcoRI fragments of 2.6 and 5.3 kb. These two fragments, as well as an homologous phage lambda VIII1 harboring about 19 kb of human DNA, were isolated from genomic libraries. Sequence analysis revealed that three different genomic hsp86 sequences had been cloned, one of them being the 5' half of a functional gene. This gene contains several introns, as compared to the entire Hsp86-encoding sequence found in lambda VIII1, which represents a processed pseudogene. Cloned hsp86 promoter, with its TATA-box and a heat-shock element upstream at nt positions -25 and -75, respectively, was functional, as verified by fusion to the bacterial chloramphenicol acetyltransferase-encoding gene and its transient expression in vivo. The typical hsp86-type heat-shock regulation was observed, i.e., significant basal activity associated with an inducibility at elevated temperatures. Furthermore, accurate and efficient in vitro transcription was initiated at this hsp86 promoter, resulting in expression of the hsp86 gene, as well as the unrelated sequences. PMID- 2591743 TI - Recombinant selection by microinjection: a simple cDNA cloning procedure for production of exclusively sense RNA transcripts. AB - A new strategy for cDNA cloning is presented, designed particularly for identification of recombinants by functional analysis, after microinjection into somatic cells. First-strand synthesis is primed by the oligodeoxyribonucleotide: (formula; see text) After second-strand synthesis and blunting, double-stranded cDNA is formed, which carries restriction sites for NotI and ApaI downstream from the coding sequence. The cDNA is ligated into a plasmid, between two promoters for phage T7 and T3 RNA polymerases. Following transfection and amplification in Escherichia coli, plasmids are extracted from the library or sublibraries. Linearisation with NotI, prior to in vitro transcription, cleaves the plasmids between the 3'-end of the coding sequence and the adjacent promoter and thus ensures that only sense RNAs, suitable for microinjection, are produced after addition of the RNA polymerases. Use of NotI, a rare cutter in the human genome, should ensure that the cDNA inserts are not damaged during linearisation. In the unlikely event that this does happen, a site for ApaI is also available. The method is demonstrated for the human adenine phosphoribosyltransferase-encoding gene. PMID- 2591744 TI - Sequence of human eosinophil-derived neurotoxin cDNA: identity of deduced amino acid sequence with human nonsecretory ribonucleases. AB - Several clones of human eosinophil-derived neurotoxin (EDN) cDNA have been isolated from a lambda gt10 cDNA library prepared from mRNA derived from noninduced HL-60 cells. The amino acid (aa) sequence deduced from the coding sequence of the EDN cDNA is identical to the aa sequence of urinary nonsecretory RNase. Comparison of the aa and/or nucleotide (nt) sequences of EDN and other proteins possessing ribonucleolytic activity, namely bovine seminal RNase, human and rat pancreatic RNases, eosinophil cationic protein (ECP), and human angiogenin, shows extensive identity at half-cystine residues and at aa of active sites. Differences in aa sequences at the active sites are often the result of single nt changes in the codons. The data presented here support the concept of a RNase gene superfamily containing secretory and nonsecretory RNases, angiogenin, EDN and ECP. PMID- 2591745 TI - Localization of a transcription start point within the human Hinf element. AB - The Hinf family is a repetitive nucleotide sequence of the human genome. Certain structural features of Hinf DNA resemble the eukaryotic RNA polymerase II promoters. Therefore, we studied the ability of the Hinf element to function as a transcriptional promoter in mammalian cells. We placed the Hinf element upstream from the thymidine kinase-encoding (tk) sequence in a plasmid construct, pAC401 and introduced it into Ltk- mouse cells. The Hinf-tk plasmid was able to transform Ltk- cells to Tk+ phenotype. In another plasmid construct, pAC Hinf neo, the Hinf element was inserted upstream from the sequence encoding neomycin (Nm) resistance (neo), and this plasmid was able to confer Nm resistance to HeLa cells. The nature of transcription initiation of the tk gene in four of the Tk+ clones transformed by pAC401 was examined by S1 nuclease analysis, and the transcription start point (tsp) for the tk gene in these clones was mapped within the Hinf element. The same tsp in the Hinf element was found in HeLa cells. Our studies show that the Hinf element functions as a weak promoter. PMID- 2591746 TI - Chromosomal and molecular analysis of 5S RNA gene organization in the flax, Linum usitatissimum. AB - The 5S rRNA genes (5S DNA) comprise up to 3% of the flax genome. Large copy number changes in 5S DNA have been observed in flax genotrophs. We have characterized the chromosomal and molecular organization of this large gene family. In situ hybridization studies indicate the 5S DNA is distributed over many chromosomes, unlike most plants studied to date. Eleven genomic clones were isolated and characterized. All but one of the clones contain both 5S DNA and non 5S DNA. The homology of the 5S DNA of each clone, to a previously isolated flax 5S plasmid clone (pBG13), was determined. Five groups of 5S DNA were identified based on shared identity and repeat unit size. Group-1 and group-2 clones are the most abundant in terms of genomic representation. The remaining groups are significantly different from the previously described flax 5S DNA and are in low representation in comparison to group-1 and group-2 5S DNA. The results establish the presence of several groups of 5S DNA which are distributed over many chromosomes. The extent of identity shared among these groups to pBG13, indicates a high degree of divergence between the different groups. PMID- 2591748 TI - Driver's license restrictions: approach with caution. PMID- 2591749 TI - Reflections on a practice going geriatric. AB - Whether they want to or not, many physicians are becoming geriatricians--and maybe they should count their blessings. PMID- 2591747 TI - Endogenous and heavy-metal-ion-induced metallothionein gene expression in salmonid tissues and cell lines. AB - Endogenous levels of metallothionein (MT) mRNA were detected by RNA probes in several somatic and germ-line tissues of rainbow trout, such as eggs, ovaries and immature testis. These levels may be related to metal-ion homeostasis in the observed tissues. The induction kinetics of trout MT isoform B (MT-B) mRNA were studied after single intraperitoneal injections of CdCl2, CuCl2 and ZnCl2. MT-B mRNA was induced within 12 h in liver, kidney, spleen and gills. However, over the 48-h experimental period, the kinetics of MT-B mRNA accumulation differed in response to the three metal salts, possibly due to differential handling of the salts by these tissues. Multiple metal-salt injections induced high levels of MT B mRNA in the four tissues studied. In the rainbow trout hepatoma cell line, ZnCl2 was a better inducer of the MT-B gene, as compared to CdCl2 and CuCl2. The expression of the exogenous trout MT-B promoter in Chinook salmon embryonic cell line indicates the presence of MT regulatory factors. In contrast, the endogenous MT genes in these cells are quiescent, possibly due to the methylation of their promoter region. PMID- 2591750 TI - [Mathematical prediction of indicators of toxicity and hygienic standardization of phenylurea compounds]. AB - The relation between physical and chemical constants and toxicometric indicators has been used as the basis of mathematical simulation both of separate indices of toxicity and preliminary safety exposure levels of the compounds of phenylurea series, thus it becomes possible to apply the derived mathematical links for rapid hygienic norm-setting of new substances of the above group. Multiple regression equations have been derived for calculating LD50, Limac, Limch and MACs of phenylurea in the work zone air. The proposed approach to MAC substantiation provides the opportunity to predict MACs for similar chemical compounds in the work zone air with sufficient accuracy. PMID- 2591751 TI - [Hygienic prerequisites of the construction of equipment for vocational education of schoolchildren]. AB - Improvement of the industrial training programme needs optimization of tooling. The above problem can be solved through a systems approach. Special methodological procedures based on the comparison of actual values of physiological functions with the work's physiological value should be utilized for the hygienic assessment of the tooling used by schoolchildren. PMID- 2591752 TI - [Methods of reducing the amount of pediculocide residues on bed linens to safe levels]. AB - The means for reducing the residue of organophosphorous and pyrethrin pediculicides on the fabric to safety levels have been developed due to the use of gas and liquid chromatography. The proposed procedures include linen washing after its pediculicidal treatment. Optimal conditions for the removal of the above substances from the fabric have been set forth. Actual quantity of pediculicides on the fabric after its treatment has been identified. PMID- 2591753 TI - [Providing and improving information services in the public health and bacteriologic laboratories of the urban sanitary and epidemiologic stations]. PMID- 2591754 TI - [Prevention of alcoholism among forestry workers]. PMID- 2591755 TI - [Medico-hygienic preparation of young couples for marriage]. PMID- 2591756 TI - [Use of centigrade nomograms for evaluating the physical development of children]. PMID- 2591757 TI - [Carcinogenic hazard of nitrosodimethylamine in humans]. AB - Literary data on the evaluation of carcinogenic hazard of nitroso compounds and in particular nitrosodimethylamine (NDMA) were analyzed. Their hazardous impact on humans was confirmed. The study results enabled one to set the total safety dose of NDMA at 0.1 mg per animal, to determine NDMA safety levels in environment, i.e., atmospheric air and water reservoirs, at. 0.0001 mg/m3 and 0.0001 mg/l, respectively, and to establish the total human safety level of NDMA at less than 0.002 mg per day. PMID- 2591758 TI - [Determining the levels of formaldehyde in the air in the presence of furfural]. PMID- 2591759 TI - [Sorption methods of isolating polycyclic aromatic hydrocarbons in their quantitative analysis in gaseous media]. PMID- 2591760 TI - [Chromatographic analysis of the herbicide cycloate in the soil]. PMID- 2591761 TI - [A method of determining the levels of nitrates in fruit and vegetables using gas liquid chromatography]. PMID- 2591762 TI - [Gas-chromatographic analysis of contaminated water: the methods of sample preparation]. PMID- 2591763 TI - [Photocolorimetric analysis of water-soluble proteins]. PMID- 2591764 TI - [Improving the sanitary control of swimming pools]. PMID- 2591765 TI - [Improving the methods of popularization of medical knowledge]. PMID- 2591766 TI - [Hygienic characteristics of the contamination of atmospheric air by mercury]. PMID- 2591767 TI - [Data for revising the MPEL of beryllium in drinking water]. PMID- 2591769 TI - [Problems of standardization of phosphorus-32 in reservoir water]. PMID- 2591768 TI - [Hygienic regulation of the p-chlorobenzalchloride level in reservoir water]. PMID- 2591770 TI - [Electrohydraulic disinfection of waste water and its biological effect on animals]. PMID- 2591771 TI - [Evaluation of dyed substances in purified waste water in experiments on water organisms]. PMID- 2591772 TI - [Effect of a non-homogenous constant magnetic field on reproductive function]. PMID- 2591773 TI - [Complex hygienic evaluation of the production and use of artificial amide leather]. PMID- 2591774 TI - [Hygienic evaluation of the number of stories at children's day care establishments]. PMID- 2591775 TI - [Analysis of zinc requirements of sportsmen]. PMID- 2591777 TI - [Radiation-hygienic complex of monitoring the handling of sources of ionizing radiation]. PMID- 2591776 TI - [Modifying effect of the chemical components of dust on the induction of lung tumors by physical and chemical carcinogens (experimental study]. AB - Chronic inhalation intake of benzo(a)pyrene (BP) and polonium-210 (210Po) together with aluminum oxide caused increase of tumor formation in the lungs of mice. Synergy of BP and 210Po carcinogenic effect was pointed out, it was characterized by summation and possible effect involution by tumor development rates and the duration of the latent period. BP and 210Po carcinogenic effectiveness depended on the type of dust carrier and probably on the presence of silicon dioxide and also carcinogenic metals. It was pointed out that further studies were necessary to determine an etiologic role of mineral dust chemical components in carcinogenic activity of the above substances and also carcinogenic effectiveness of dusts as carriers of chemical carcinogens and alpha-active radionuclides. PMID- 2591778 TI - [Toxicology and hygienic standardization of the new insecticide neopinamine]. AB - Proceeding from the experimental study of neopinamine insecticide toxicity its hygienic standardization was carried out. Since neopinamine had moderate toxicity under its acute and chronic effect and different routes of body intake, its accumulation was absent and its impact was selective in the occurrence of aftereffects, this preparation was attributed to the third class of danger. Neopinamine MAC in the workplace air was recommended at the level of 5 mg/m3. PMID- 2591779 TI - [Dynamics of the cardiac rhythmogram during various types of exams]. PMID- 2591780 TI - [Value of the diagnosis of premorbid conditions of the digestive system in the promotion of a healthy life style]. PMID- 2591781 TI - [The health education of stock breeders]. PMID- 2591782 TI - [Workers' health and various approaches to its quantitative evaluation]. AB - A new approach to the assessment of health status of the working people is proposed. Qualitative determinations of the "cost" of body adaptation to occupational and nonoccupational factors could be used as a health standard. The adaptation "cost" was calculated by means of integral indicators, characterizing body system response to human vital activity factors. Some approaches to the development of the "alphabet" of human functional states formed during the process of adaptation to vital activity factors. The proposed methods of assessing health levels can be used in the development of automated systems for mass prenosologic examinations and dispensarization of the population and also in workers' health management. PMID- 2591783 TI - [Methods of determining formaldehyde levels in the air]. PMID- 2591784 TI - [Determining the values of threshold levels of the effects of harmful substances]. PMID- 2591785 TI - [Fixation of dust samples during photometric analysis of the levels of opaque aerosols]. PMID- 2591786 TI - [A method of classifying toxicometric parameters of harmful substances]. PMID- 2591787 TI - [A bioautographic method of analyzing trichothecene mycotoxins in grain and its products]. PMID- 2591788 TI - [A method of experimental study of conditioned reflexes]. PMID- 2591789 TI - [Effectiveness of the cooperation between member countries of the COMECON in the field of water hygiene]. PMID- 2591790 TI - [Extended use of sodium hypochlorite as a disinfectant]. PMID- 2591791 TI - [Improving the design of departments of radiation hygiene at sanitary epidemiologic stations]. PMID- 2591792 TI - [Atomic absorption analysis of mercury in soil using the "Rtu't-101" analyzer]. PMID- 2591793 TI - [Ozone formation during air decontamination by UV irradiation in ventilation channels]. PMID- 2591794 TI - [Hygienic significance of pathomorphologic changes of the organs in albino rats in studying the embryotoxic effect of fenuron]. PMID- 2591796 TI - [Hygienic regulation of tri(chloroethyl)phosphate in the water]. PMID- 2591797 TI - [Terpenes in waste water from the Baikal paper mill and in the water of the Baikal lake]. PMID- 2591795 TI - [Hygienic regulation of ethylene glycol monomethacrylic ether in reservoir water]. PMID- 2591798 TI - [Somatotypes in evaluating the physical development of 11-year-old schoolchildren]. PMID- 2591799 TI - [Physical development of young illegitimate children]. PMID- 2591800 TI - [Study of the combined effects of lead and cadmium on experimental animals]. PMID- 2591801 TI - [Sorption of fumes of sterilizing mixtures of ethylene oxide and methyl bromide by polymers for medical use]. PMID- 2591802 TI - [Medical hygiene measures in organizing shift work taking circadian rhythms into account]. AB - Nowadays the share of workers engaged in shift work in the GDR constitutes 37% of all those working in production. It is pointed out that this share will increase. Scientific validation of necessary activities aimed at the organization of material, time-dependent and social labor conditions for those working by shifts has been one of the most important objectives of the study in occupational hygiene of the GDR. Circadian rhythms and associated biological and social desynchronization processes are of primary importance for planning a shift cycle, determining favorable individual preconditions to shift work, assessing health impact of detrimental factors combined with shift labor in the production process. The latest research on the evaluation of the shift system of work, involving prolonged shifts, and on the impact of individual daily rhythms on fitness to shift work is presented. PMID- 2591803 TI - [The body function of engineering and technical workers in modern metallurgic production]. AB - Labor activity of engineering and technical personnel under modern production conditions is characterized by the impact of some psychoemotional, physical, chemical and other factors. The study findings demonstrated the characteristics of these factors' effect on the functional state of metallurgical workers' body systems and organs. The characteristics of engineering and technical personnel's health state and morbidity rates were set forth. PMID- 2591804 TI - [Biological effects of the action of permanent magnetic fields of various intensities]. AB - The data on biologic effect of constant magnetic fields (CMF) of various intensity were presented. It was shown that animals (white rats) exposed to CMF of 1600-400 kA/m experienced moderately distinct functional changes, manifested by raising excitability of the CNS spinal sections, hypothermic reactions and variations in some blood indices. CMF of 80 kA/m and lower produced no unfavorable effect on animals. It was supposed to use the obtained data in the improvement of CMF hygienic standardization. PMID- 2591805 TI - [Clinical variants of the disease caused by exposure to radio-frequency electromagnetic fields]. AB - Clinical data on the characteristics of the course of the disease caused by microwave radiation are presented. It is assumed that the characteristics of the clinical picture of the disease are specified by radiation "geometry". PMID- 2591806 TI - [Cerebral hemodynamics in persons subjected to exposure to intensive industrial noise]. AB - Correlation of cerebral hemodynamic disorders, levels of arterial pressure and degree of hearing loss was examined by means of calibrometry of retina vessels in 318 mechanical engineering workers exposed to intensive industrial noise. Workers with hearing impairments had higher rates of arterial hypertension than those with preserved hearing. Circulatory disorders in the cerebral microvascular system were detected both for elevated and normal arterial pressure and they were caused primarily by arteriole hypertonus. As the hearing analyzer function decreased, the trend to the reduction of tone disorders appeared. PMID- 2591807 TI - [Individual typological characteristics of the cardiovascular reaction to partial body cooling in workers on field-watch assignments]. AB - Due to the use of a cluster analysis 5 types of the individual cardiovascular response to hand local cooling and of cold thermosensitivity were identified. The following groups were determined: I. non-cold-adapted group with elevated cold thermosensitivity and vascular response to local cooling, young age and short term length of service on watch; 2. the group with different levels of thermal adaptation on the verge of the 3-year period of work, the age being similar; 3. the group with extremely low cold thermosensitivity and moderate vascular response to local cold. The group is characterized by long-term length of service and positive forecast as to individual work under subextreme conditions of being on dispatch watch. PMID- 2591808 TI - [Protection of the respiratory organs while working in the cold]. AB - On the basis of new progressive anisotropic porous materials a mask with a recuperator which effectively heats the inhaled air by means of breathed-out air energy utilization has been created. The mask can decrease the load on human adaptation mechanism to unfavorable climatic effect of high latitudes where cold is a major unfavorable factor. Such a mask is a highly effective means of individual human protection from cold, providing the possibility to improve workers' labor conditions. PMID- 2591809 TI - [Physiologic hygiene characteristics of job placement following the radical treatment of breast cancer]. AB - Life expectancy of patients with the most prevalent oncologic disease, i.e., breast cancer, has been increased due to the latest achievements in its treatment. The majority of such patients have favorable forecast and come back to work. At the same time it is pointed out that the treatment course is accompanied by some changes in the main life-sustaining and effect-dependent functions. Coming back to work with lowered work capacity and working under unfavorable labor conditions, such patients are in many cases exposed to the effect of various occupational factors and their professional activity. Proceeding from the principles of adequate job selection, one must avoid absolutely counter indicative factors and restrict work load. PMID- 2591810 TI - [The efficacy of regulating sleep by physical exercises performed at a set time of the day]. AB - Work capacity peaks of sailors with disorders in falling asleep didn't correspond to time of being on watch and recessions in work capacity with the time of sleep. Dose-dependent physical load 12 hours prior to bedtime was quite effective for treating disorders of falling asleep. PMID- 2591811 TI - [Hygienic aspects of the industrialization and intensification of chemical seed protection. Achievements and problems]. AB - Design improvement of machines and devices for seed decontamination with account of the proposed hygienic recommendations promoted sanitation of operators' working conditions. Introduction of progressive technology (damping, inlaid work) enables one to reduce pesticide application and to decrease ecologic hazard of seed chemical protection. PMID- 2591812 TI - [Characteristics of the clinical manifestations of inactive pulmonary coniotuberculosis]. AB - Analysis of clinical development of nonactive coniotuberculosis in 167 patients showed that pneumoconiosis, complicated by tuberculosis, grew progressively worse as to its stage, form and incidence. Intoxication syndrome in such patients was of specific tuberculosis character and the above patients could be quite efficiently treated by antituberculosis preparations. PMID- 2591813 TI - [A method of calibrating the aluminum wedge for x-ray photometric research in occupational pathology]. AB - Calibration procedure of aluminum wedge by optical density gradient of its X-ray image compared to density of standard bone wedge was described for X-ray photometric studies. Calibration of standard aluminum provided the opportunity to determine skeleton mineralization not only by wedge depth but also by units of mineral salt concentrations. PMID- 2591814 TI - [A photometric method for determining formaldehyde in the air using phenol formaldehyde resins]. AB - Photometric procedure of methanol determination based on its reaction with phenyl hydrazin and dinitride sulfanilic acid was developed. The procedure was highly sensitive (0.1 microgram in the analyzed volume) and selective in the presence of phenol, furyl alcohol, methanol and furfurol. PMID- 2591815 TI - [Mucosal function of the upper respiratory tract in gas cutters]. PMID- 2591816 TI - [Evaluation of the significance of the body uptake of natural radionuclides with manufacturing dust at industrial enterprises]. PMID- 2591817 TI - [Characteristics of the dust factor in the manufacture of artificial mineral fiber substances (silicon carbide)]. PMID- 2591818 TI - [The relation of the toxicity of copper phthalocyanines to their distribution in blood serum proteins]. PMID- 2591820 TI - [The use of transvenous destruction of the atrioventricular junction for correcting hemodynamic disorders caused by ventricular-atrial conduction]. AB - The authors studied disorders of central and intracardiac hemodynamics occurring in electrostimulation of the ventricles attended by retrograde stimulation of the cardia. The experiments were conducted on 8 anesthetized dogs in whom, after disclosure of intact ventriculoatrial conduction, transvenous destruction of the atrioventricular junction was performed. Clinical study was carried out in 12 patients with continuous electrostimulation of the ventricles which caused retrograde stimulation of the atria, and in 19 patients with supraventricular tachyarrhythmia who were subjected to transvenous endocardial destruction of the atrioventricular junction. Due to the development of severe hemodynamic disorders in electrostimulation of the ventricles attended by retrograde stimulation of the atria the last named condition should be changed to ventriculoatrial dissociation which promotes growth of contractile activity and stroke volume of the left ventricle. Transvenous destruction of the atrioventricular junction is a reliable method for blocking retrograde conduction. PMID- 2591819 TI - [Right-to-right arteriovenous shunting in the compensation of pronounced disorders of pulmonary ventilation]. AB - The mechanism of compensation for disorders of ventilation after pulmonary tissue resection is discussed. It is shown that these disorders are attended with reduction of arterial pulmonary blood flow and that angiospasm occurs in the postcapillary part of the vascular channel of pulmonary circulation. The compensatory effect is achieved by a right-to-right arteriovenous shunt which prevents extreme increase of pressure in the pulmonary artery in ventilation disorders. PMID- 2591821 TI - [Diagnosis and treatment of the respiratory distress syndrome during surgery in children under artificial circulation]. AB - The authors examined 152 children with congenital heart diseases complicated by pulmonary hypertension. 109 patients were operated on under conditions of hypothermic perfusion and 43--under deep hypothermia with extracorporeal circulation. Combination of disturbed mechanics of respiration and gas exchange was determined as the respiratory distress syndrome. The initial value of lung expansibility was found to be in inverse proportion to the degree of pulmonary hypertension. With the increase of pulmonary hypertension lung expansibility reduced before extracorporeal circulation and gas exchange became worse. Hypothermic perfusion at volumetric rates of 1.7-2.55 l/min/m2 led to diminished lung expansibility in the early postperfusion period of the operation, the mechanics and gas exchange grew worse. In patients who underwent operation under conditions of deep hypothermia the values of lung expansibility and gas exchange were stable. The incidence of the respiratory distress syndrome was 56.3% after hypothermic perfusion and 7.2% after deep hypothermia. PMID- 2591822 TI - [A new approach to the creation of heart valve xenograft bioprostheses resistant to calcification]. AB - The calcium binding activity of xenograft tissue in stages of modification with papain, diphosphonates, and heparin was studied on a model of accelerated calcification in subcutaneous implantation of cusps of pig's aortic bioprostheses to 42 rats. In immobilization of 3-amino-1-oxypropylidendiphosphonic acid and xydiphon the amount of calcium in the implants reduced 50 times as compared to the control. The first stage of ion-covalent heparin immobilization--treatment with albumin--increased the calcium-binding activity of the biomaterial, but subsequent heparinization reduced again the calcium content in the cusp tissue to the level attained in the stage of diphosphonate immobilization. The results of the chemical analysis correlated with the findings of morphological examination. Besides, the new method of treatment made it possible to increase the strength of the biological tissue by 20%. This method of storage of bioprostheses is promising for clinical approbation. PMID- 2591823 TI - [Therapeutic procedures in the middle lobe syndrome]. AB - From study of the case records of 113 patients with isolated affection of the middle lobe or lingular segments of the left lung the authors believe that nonspecific inflammatory diseases of the lungs are the most frequent cause of the development of the syndrome. Tomography and bronchography of the involved lung play the principal role in the diagnosis of the middle-lung syndrome. The etiological factor is verified by the findings of tracheobronchoscopy. The authors consider surgery to be the main method of treatment of the middle-lobe syndrome or syndrome of the lingular segments. PMID- 2591824 TI - [The use of a plasma unit in surgery of the lung and pleura]. AB - On the basis of 35 experiments on dogs and clinical experience in operations on the lungs and pleura in 11 patients with the use of a plasma stream and special miniature nozzles the authors revealed the following: reliable hemostasis and aerostasis in cutting pulmonary tissue and pleura; tissue wounds inflicted by a stream of plasma are sterile; the zone of coagulation necrosis is no larger than 1 mm; healing occurs predominantly according to the type of aseptic productive inflammation with growth of connective tissue into the thermal crust. The operation in all patients was successful, no complications developed. The design of the BCBY-160 plasma apparatus should be improved to make it more compact, to reduce its size. PMID- 2591825 TI - [Endoscopic laser surgery of the trachea and bronchi]. AB - The authors conducted 76 endoscopic laser operations on 51 patients with malignant (18) and benign (9) tumors and cicatricial stenosis (24) of the trachea and bronchi. An AYG laser (on and yttrium aluminium garnet with neodymium) with a power of up to 27.5 Wt was used as the source of laser radiation. Intraoperative complications were recorded in 2 (2.6%) cases. The immediate results were good in 88.2%, satisfactory in 3.9%, and poor in 5.9% of patients. It is concluded that the endoscopic use of the AYG laser for the destruction of tumors, cicatrices, and granulations in the tracheal and bronchial lumen both as the first stage of surgical treatment and as an independent palliative method in inoperable patients is highly effective and safe. PMID- 2591826 TI - [Plastic surgery of the mitral valve in patients undergoing closed commissurotomy]. AB - The authors report on 64 valve-preserving operations conducted under conditions of extracorporeal circulation in patients with a history of closed mitral commissurotomy (59 patients with restenosis of the mitral orifice and 5 patients with iatrogenic mitral insufficiency); hospital lethality was 14%. The peculiarities of the diagnosis and operative techniques of the second intervention in this pathological condition are discussed in detail. From study of the immediate postoperative results the authors conclude that during the second operation after closed mitral commissurotomy the patient's own valve can be preserved in 30-35% of cases. They claim that restenosis of the mitral orifice and iatrogenic mitral insufficiency are a complicated form of mitral valvular disease and should be corrected on an open heart with extracorporeal circulation. PMID- 2591827 TI - [Characteristics of the use of radiation from various types of lasers in the surgical treatment of patients with pleural empyema]. AB - The article analyses experience in the use of beams of various types of lasers in treatment of 152 patients with different forms of pyothorax of tuberculous and nontuberculous origin. Semiconductor and carbon dioxide laser devices were used in the stages of surgical treatment. Methods for the use of lasers in the pre- and postoperative periods and during the operation are described. With the use of laser beams in the stages of surgical treatment the traumatic character of the intervention is lessened, blood loss during the operation reduced, the walls of the empyema are sterilized effectively, the incidence of postoperative complications diminishes, and the clinical efficacy of surgical management of this severe contingent of patients is improved. PMID- 2591828 TI - [The differential use of fibrinolysis activators and inhibitors in treating acute abscesses and gangrene of the lungs]. AB - The authors examined 25 patients with acute abscesses and gangrene of the lungs to study the condition of the phagocyte system and its effect on processes of fibrin formation and destruction in the focus of inflammation. They found marked increase of the number of polymorphonuclear leucocytes and decrease of alveolar macrophages in lavage fluid of the diseased lung. The fibrinolytic, procoagulant, and oxygen-dependent metabolic activity of phagocytes was increased. With the degree of these changes and the clinical and endoscopic signs of the activity of the inflammatory process taken into account, the choice of the fibrinolysis activators and inhibitors for endobronchial administration can be differentiated and the results of treatment improved. PMID- 2591829 TI - [The recurrence of dysphagia in patients with neuromuscular diseases of the esophagus with normal or low pressure indices in the physiological cardia]. AB - The authors examined 47 patients with recurrent cardiospasm or achalasia of the cardia after dilatation or operations in normal or low esophago-gastric pressure gradient. The findings of clinical, radiological, endoscopic, and esophagomanometric examination of patients are shown. The article discusses the results of drug treatment, pneumatic dilatations, operative interventions in this group of patients. The probable causes of the development of dysphagia in normal values of pressure in the physiological cardia are considered. PMID- 2591830 TI - [Preoperative diagnosis of residual tumor in esophageal cancer following radiation therapy]. AB - The authors analyse 100 operations for resection of the esophagus after radiotherapy. Morphological examination before irradiation showed squamous cell carcinoma in all patients. Difficulties arise in the diagnosis of a residual esophageal tumor after radiotherapy, as a result of which 11 (14.5%) of 76 patients irradiated with a dose of 30-40 GY and 1 (4.2%) of 24 patients who received a dose of 50-70 Gy were exposed to the risk of a surgical intervention in the absence of morphological signs of a tumor in the removed esophagus. The difficulties of the diagnosis are due to resorption of the tumor under the effect of radiotherapy, its exophytic component in particular, the frequent submucosal position of the tumor, signs of therapeutic pathomorphosis of the tumor, and fibrosis of the esophageal wall. PMID- 2591831 TI - [A method of myocardial electrode implantation for permanent electrocardiostimulation]. PMID- 2591832 TI - [A retractor for surgery of the lungs via an transsternal approach]. PMID- 2591833 TI - [Balloon valvuloplasty in congenital aortic stenosis]. AB - The authors discuss their experience with balloon valvuloplasty (BVP) in aortic valvular stenosis (AVS) in 3 patients aged 10 months, 15 and 16 years. BVP was carried out in all of them with exposure of the right subscapular artery. Left ventricular (LV) systolic pressure before BVP was 198 +/- 45 mm Hg on the average, systolic pressure gradient between the LV and the aorta was 102-32 mm Hg. After BVP systolic pressure in the LV reduced by 26.5% and was 146 +/- 27.8 mm Hg, the systolic pressure gradient between the LV and the aorta reduced by 64.8% and was 36.0 +/- 7.5 mm Hg. No increased regurgitation of contrasted blood through the valve into the LV was demonstrated by repeated aortography. Complications connected with BVP were not encountered. Thus, BVP may be an alternative to surgery in congenital AVS. This method is evidently indicated for patients of early age with AVS, which allows operations with extracorporeal circulation to be avoided. According to the authors, BVP is expedient in congenital AVS in older patients when the diameter of the aortic valvular ring is less than 20 mm. PMID- 2591834 TI - [A case of accurate diagnosis and successful correction of a rare anomaly of the coronary sinus]. PMID- 2591836 TI - [A case of late successful treatment of a patient with a penetrating heart wound and infected hemopericardium]. PMID- 2591835 TI - [Surgical treatment of a traumatic defect of the interventricular septum after a knife wound of the heart]. PMID- 2591837 TI - [Hemolytic anemia following aortic valve replacement with an Emix prosthesis]. PMID- 2591838 TI - [Circular resection of the left primary bronchus with the application of a tracheobronchial anastomosis via the transsternal-pericardial approach]. PMID- 2591840 TI - Differential diagnosis SIDS/non-SIDS on the basis of histological findings of petechial thymus hemorrhages. AB - Petechial thymus hemorrhages are found most frequently in SIDS (87%), and very much more rarely in fetuses after abortion and stillbirths (55%) as well as in perinatal deaths (40%). In these groups, there was a uniform histological bleeding pattern with emphasis on the cortical zone. In non-SIDS deaths of natural causes or extrinsic suffocation in babies and infants, it could be demonstrated in 39%. In extrinsic suffocation, the thymus hemorrhages were mostly less pronounced in quantitative terms than in SIDS. In non-SIDS (without extrinsic suffocation), a hemorrhage pattern different from SIDS could be detected with hemorrhagias of different sizes and irregularly distributed over the cortex and medulla. PMID- 2591839 TI - [Pneumonectomy with atrial resection in a patient with lung cancer with concomitant atherosclerotic encephalopathy]. PMID- 2591841 TI - Incised wound margins caused by steel blades. Scanning electron microscopy to determine wound direction. AB - The aim of this paper has been to check the diagnostic ability of Scanning Electron Microscopy (S.E.M.) to determine wound direction. We have studied incised wound margins caused by steel blades in human skin samples from cadavers by S.E.M. It was found that a lateral accessory tail existed in 65% of the entrance edges. This finding was recorded in all the cases when wound direction was perpendicular to Lancer's lines of the skin area in which the wound was located. No similar finding in the exit tails was noticed. The depth and length of the wound margins was less accurate an index of the wound direction than a lateral accessory tail. We think that this finding could be useful in determining the entrance margin in incised wounds. PMID- 2591842 TI - A comparative study of the microbiological contamination of postmortem blood and vitreous humour samples taken for ethanol determination. AB - Postmortem blood and vitreous humour samples were taken from each of 51 subjects. None of the vitreous humour samples contained large numbers of bacteria or fungi, whereas many micro-organisms were detected in 32 of the blood samples. The results of the microbiological examinations provided useful information for the interpretation of some ethanol levels that might otherwise have been misleading. PMID- 2591844 TI - [Progress in geriatrics for routine general practice]. PMID- 2591843 TI - Chronic intoxication by heroin; histopathological effects on seminiferous tubules. AB - Seminiferous tubules from heroin abusers and from rats chronically intoxicated by heroin samples presented a striking reduction in the thickness of the germinal epithelium. Light and electron microscopical studies showed a considerable increase of lipids and phagosomes in Sertoli cells, disorganization of their junction complexes, detachment of immature germ cells which appeared free in the tubular lumen, and formation of giant multinucleate spermatids. These alterations point out that Sertoli cells could be the target element for the toxic effect of heroin samples on the seminiferous epithelium. PMID- 2591846 TI - [The retirement community is rare among residences for the aged]. PMID- 2591845 TI - [Geriatric day clinics and rehabilitation]. AB - If the present development of our population is not to result in a continued increase in care-requiring elderly people, the building and expansion of geriatric rehabilitation institutions is a matter of urgency. Numerous studies, some of which carried out in our own country, show how successful geriatric rehabilitation can be. Prerequisites are, apart from appropriately equipped facilities, the proper selection of those requiring care, adequate numbers of properly qualified personnel, and early initiation of any treatment needed. Thus, 70 to 80% of those originally scheduled for admission to an old persons' nursing home can be enabled to live more or less independently at home. Apart from geriatric hospitals, geriatric day clinics offer optimal possibilities for rehabilitation. They combine therapeutic effectiveness and economy with the advantage that, during treatment, the elderly person is not completely taken out of his familiar surroundings, which results in an improvement in his motivation to get well again quickly. At the same time, complicating diseases, such as, for example, diabetes mellitus, can be treated under conditions closely similar to those of the patient's subsequent day-to-day situation. In this sense, geriatric day clinics are not only desirable, but urgently needed institutions. PMID- 2591847 TI - [The long-term management of patients following surgery of congenital heart defects--in particular postoperative ventricular arrhythmia]. PMID- 2591848 TI - Growth and development of rat oocytes in vitro. AB - Rat oocytes from preantral follicles have been shown to grow and acquire meiotic competence in vitro. Follicles were isolated by enzymatic digestion of ovaries from infant (10- or 11-day-old) Wistar rats. Follicles were cultured for up to 20 days in Minimum Essential Medium (MEM) supplemented with 2 mM hypoxanthine to maintain meiotic arrest. When cultures were begun, oocytes were in midgrowth phase (40-45 microns diameter), and were incapable of undergoing meiotic maturation when placed in hypoxanthine-free MEM. Oocytes grew and acquired meiotic competence during culture for 20 days attaining mean diameters of 62.6 +/ 0.6 microns and 61.1 +/- 0.6 microns in two experiments. Germinal vesicle breakdown (GVB) occurred in 60-70% of oocytes when transferred to MEM without hypoxanthine. Concomitant with oocyte growth and maturation were spontaneous increases in follicular production of progestins, androgens and estrogens. When oocytes grown and matured in this system were inseminated in vitro with epididymal sperm, 36.1% and 25.8% were penetrated by one or more sperm in two experiments. However, fertilization was not generally normal with multiple penetrations and abnormal numbers of pronuclei (one or three) being common, suggesting that in these oocytes cytoplasmic maturation was incomplete or abnormal. In the two experiments, normal fertilization (two pronuclei and one sperm tail in the vitellus) occurred in 34.6% and 47.1% of penetrated oocytes with development of these apparently normal zygotes to two-cell embryos being 66.7% and 62.5%, respectively. PMID- 2591849 TI - Effects of glutathione (GSH and GSSG) and glutathione reductase (GR) on zona-free hamster oocyte ability to decondense human sperm. AB - Effects of reduced glutathione (GSH), oxidized glutathione (GSSG), or glutathione reductase (GR) supply were studied on the ability of hamster oocytes to be fertilized by human sperm. Zona-free oocytes were pretreated with these compounds prior to sperm insemination. Oocyte pretreatment with high concentrations of GSH or GSSG (50 or 100 mM, 30 min) significantly increased the penetrated oocyte rate (PR). Polyspermy was not increased except when high concentrations of GSH (100 mM) were used. Incubation of oocytes with GR (1 or 10 IU/ml) prior to sperm insemination induced increasing dose-dependent PR. Polyspermy increased significantly with 10 mM GR in oocyte incubation medium. Oocyte incubation for 30 min with the sulfhydryl blocking agent iodoacetamide (1 mM) led to a drastic decrease in oocyte penetration and in polyspermy. Our results demonstrate an original way to increase the efficacy of human-hamster heterospecific fertilization. Various hypotheses are discussed explaining these observations which open new investigations for heterospecific and homospecific in vitro fertilization. PMID- 2591850 TI - Hamster oocyte penetration tests with oocytes frozen in propanediol: comparison with non-frozen oocytes. AB - Hamster oocytes were frozen using a 1,2-propanediol-sucrose procedure, which resulted in over 90% survival. After thawing and zona removal the oocytes were compared with non-frozen oocytes in a zona-free hamster egg test employing spermatozoa from human semen donors and suspected infertility patients. Similar data were obtained, indicating that propanediol-sucrose frozen hamster eggs may be used in place of fresh eggs for convenience and to avoid scheduling problems. PMID- 2591851 TI - Ultrastructural and histochemical changes in the murine zona pellucida during the final stages of oocyte maturation prior to ovulation. AB - The ultrastructural morphology of the mouse zona pellucida was studied in preovulatory follicles from the ovaries of immature mice treated with exogenous gonadotrophins. The ovaries were fixed in the presence of cetylpyridinium chloride, which precipitates carbohydrates, so that their loss during fixation and processing is substantially reduced. The semi-thin araldite sections obtained from osmicated material were viewed by conventional light microscopy, while the ultra-thin sections were examined by transmission electron microscopy. A parallel series of semi-thin sections of non-osmicated ovaries was deresined and subsequently stained with periodic acid Schiff (PAS). The morphological appearance of the zona pellucida in preovulatory oocytes changed during the final stages of oocyte maturation. A close correlation was observed between the ultrastructural appearance of the zona pellucida and that observed following PAS staining during the period studied. Real differences were observed in the location, density, and distribution of glycoconjugates within the zona pellucida during the final stages of oocyte maturation prior to and immediately following germinal vesicle breakdown. Similar changes in the zona were observed in adult females autopsied during proestrus and oestrus. The changes in the density and distribution of glycoconjugates are likely to have important consequences for fertilization by affecting sperm-zona binding and sperm-egg interactions. PMID- 2591852 TI - Blastocyst formation and hatching in vitro following zona drilling of mouse and human embryos. AB - Hatching in vitro was studied following zona drilling of 507 two-cell mouse embryos using three methods: 1) acidic Tyrode's (AT), 2) partial zona dissection (PZD) using a sharp microneedle, and 3) zona chiseling (CH), using a large beveled needle. PZD and CH were performed while the embryos were kept in a sucrose/PBS solution. Hatching was compared to 191 unmicromanipulated controls. The incidences of cavitation and completion of hatching did not differ between groups, however more micromanipulated embryos (20-25%) hatched partially than controls (9%). The zona pellucida thinned in 59/59 (100%) control blastocysts during expansion, but in only 3/205 (2%) micromanipulated blastocysts. The hatching gap was wide in all control embryos, but smaller in 96/129 (75%) micromanipulated embryos. Partially hatched blastocysts with a "figure-8" shape were found in 59/129 (46%) micromanipulated embryos and in none of the 39 hatching controls. Hatching usually occurred a day earlier in micromanipulated embryos as 214/218 (98%) had started extruding on day 5 as compared to 20/59 (27%) control blastocysts. Fifty percent of 1-day-old human oocytes were fertilized following PZD and reinsemination and 15/31 (48%) were monospermic. Thirteen monospermic embryos cleaved, six compacted and four cavitated--of these, three extruded through the PZD incision upon expansion. The zonae did not thin and one blastocyst twinned spontaneously as it was caught between the thick ridges of the PZD hole. Results indicate that the hatching process is abnormal following zona drilling; more embryos start hatching, extrusion occurs earlier, and many become trapped which may lead to artificial twinning or the formation of trophoblastic vesicles. PMID- 2591853 TI - Developmental capacity of mouse oocytes that undergo maturation in vitro: effect of the hormonal state of the oocyte donor. AB - In a previous study, it was shown that cumulus cell-enclosed germinal vesicle (GV)-stage oocytes, isolated from pregnant mares' serum gonadotropin (PMSG) primed immature (22-24 day old) mice and that underwent spontaneous maturation in vitro, exhibited frequencies of embryonic development similar to oocytes stimulated to mature and ovulate in vivo by administration of gonadotropins [Schroeder AC, Eppig JJ, (1984) Dev Biol 102:493-497]. In the present study, the effect of the hormonal state of the oocyte donor on the capacity of in vitro matured oocytes to be fertilized and undergo pre- and post-implantation development was explored further. Oocytes were isolated at the GV-stage from the following groups of mice: 1) unprimed immature mice; 2) adult cycling mice; 3) unprimed Snell dwarf (dw) mice that have undetectable levels of growth hormone (GH), prolactin, and thyroid-stimulating hormone (TSH); and 4) primed and unprimed hypogonadal (hpg) mice that have undetectable levels of circulating gonadotropins. Oocytes maturing in vitro after isolation from normal unprimed immature or adult mice at all stages of the estrous cycle acquired full developmental capacity. GV-stage oocytes isolated from dwarf mice showed embryonic development equivalent to normal (+/?) littermate controls. Therefore, GH, TSH, or prolactin are not required during oogenesis in vivo to promote the acquisition of competence to complete embryogenesis after maturation in vitro. Oocytes from hypogonadal mice had a much reduced capacity for preimplantation development when compared with normal littermates. Administration of PMSG to the hypogonadal mice significantly increased the developmental capacity of oocytes that underwent maturation in vitro. Gonadotropins, therefore, have a beneficial effect on the oocyte's capacity for embryonic development. PMID- 2591854 TI - Ultrastructure of spermiogenesis in the gastropod Calliotropis glyptus Watson (Prosobranchia: Trochidae) with special reference to the embedded acrosome. AB - Testicular spermatozoa and sperm development in the archaeogastropod Calliotropis glyptus Watson (Trochoidea: Trochidae) are examined using transmission electron microscopy and formalin-fixed tissues. During spermiogenesis, the acrosome, formed evidently through fusion of Golgi-derived proacrosomal vesicles, becomes deeply embedded in the condensing spermatid nucleus. Two centrioles (proximal and distal), both showing triplet microtubular substructure, are present in spermatids--the distal centriole giving rise to the sperm tail and its associated rootlet. During formation of the basal invagination in the spermatid nucleus, centrioles, and rootlet move towards the nucleus and come to lie totally within the basal invagination. Mitochondria are initially positioned near the base of the nucleus but subsequently become laterally displaced. Morphology of the mature spermatozoon is modified from that of the classic primitive or ect-aquasperm type by having 1) the acrosome embedded in the nucleus (the only known example within the Mollusca), 2) a deep basal invagination in the nucleus containing proximal and distal centrioles and an enveloping matrix (derived from the rootlet), 3) laterally displaced periaxonemal mitochondria, and 4) a tail extending from the basal invagination of the nucleus. Implantation of the acrosomal complex and centrioles within invaginations of the nucleus and lateral displacement of mitochondria effectively minimize the length of the sperm head and midpiece. Such modifications may be associated with motility demands, but this remains to be established. The unusual features of C. glyptus spermatozoa, though easily derivable from "typical" trochoid sperm architecture, may prove useful in delineating the genus Calliotropis or tracing its relationship to other genera within the trochid subfamily Margaritinae. PMID- 2591855 TI - Octaploid mouse embryos produced by electrofusion polarize and cavitate at the same time as normal embryos. AB - We created enlarged octaploid mouse blastomeres by subjecting four-cell embryos to a large (greater than 2,000 V/cm) dc field of brief duration (10 microseconds). This electrofusion pulse caused three to four of the blastomeres to fuse in 60% of the embryos tested. Modifications of fusion chamber and medium enabled fusion of up to 20 embryos per pulse, greatly increasing the yield for this fusion method. The effectiveness of the electrofusion pulse depended upon such parameters as embryonic cell cycle time and the pH and temperature of the electrofusion medium. There was no discernable lag in the onset of the third cleavage division or the time of cavitation in fused blastomeres. These fused blastomeres also underwent polarization of their apical surfaces at the same time as controls in spite of their increased cell size. These results suggest that octaploid mouse blastomeres created via electrofusion divide normally through the blastocyst stage and polarize at the same time and in the same sequence as smaller control blastomeres. This suggests that the mechanisms underlying cell division, cavitation, and cortical polarization are not affected by changes in cellular size or ploidy. PMID- 2591856 TI - Gamete research: a new title ... and expansion into fertile fields. PMID- 2591857 TI - Development of chimaeric two-cell mouse embryos produced by allogenic exchange of single nucleus from two- and eight-cell embryos. AB - Synchronous or asynchronous chimaeras were produced by transplanting a single nucleus of two- and eight-cell embryos from CD-1xCD-1 or BALB/CxBALB/C albino strains into one enucleated blastomere of a late F1 (C57/BLxCBA) x F1 two-cell embryo. The cytoplasmic volume of the blastomere was reduced in some instances by 50%. These chimaeric embryos were cultured in vitro and transferred to pseudopregnant recipients. The distribution of each component to the pups and to the day-10 embryos after transfer to recipients was determined by examining their coat color and by glucose phosphate isomerase analysis, respectively. The contribution of progeny of the nuclear-transplanted cell with nonreduced cytoplast to the pups was 83% when synchronous; this proportion decreased to 43% when asynchronous because the progeny tended to migrate to the trophoblast and/or to the primitive endoderm. When the recipient cytoplast was reduced by 50%, the contribution of the nuclear-transplanted cell progeny to the pups was 79% when synchronous and 80% when asynchronous. This shows that allogenic exchange of a single nucleus at the two-cell stage by nuclear transfer is an effective procedure for producing highly asynchronous mouse chimaeras and suggests that larger and advanced blastomeres tend to be excluded from the inner cell mass of the embryo, but smaller, advanced blastomeres do not. PMID- 2591858 TI - Ultrastructural and cytochemical study of spermatogenesis in Scrobicularia plana (Mollusca, Bivalvia). AB - The ultrastructure of the mature spermatozoa and spermatogenesis of the bivalve Scrobicularia plana are described. Support cells extend from the basal lamina to the lumen of the testis and are laterally connected to the germinal epithelium. Germ cells present intercellular bridges and flagella since the spermatogonial stage. While spermatogonia and spermatocytes appear connected to support cells by desmosome-like junctions, elongated spermatids are held at the acrosomal region by support cell finger-like processes. During spermiogenesis, the acrosomal vesicle differentiates from a golgian saccule and then migrates to the nuclear apex. A microtubular manchette arising from centrioles surrounds the acrosomal vesicle, the nucleus, and the mitochondria at the time these three organelles start their elongation, disappearing after that. The mature spermatozoon of S. plana lacks a distinct midpiece because the mitochondria extend from the region of the pericentriolar complex along the nucleus anteriorly for approximately 1.4 microns. The features of this bivalve type of modified spermatozoon are compared with those of other animal groups having similar modifications. PMID- 2591859 TI - Effects of bovine mammary alpha-lactalbumin on hyperactivation and sperm-zona pellucida binding of mouse spermatozoa. AB - The effects of bovine mammary alpha-lactalbumin on the motility and zona-binding characteristics of mouse sperm were investigated. Two properties of sperm associated with capacitation, hyperactivated motility, and the ability of sperm to bind to the zona pellucida of oocytes were shown to be suppressed by alpha lactalbumin. These inhibitory effects were not accompanied by changes in the percentage of motile cells or by differences in the velocity parameters of the hyperactivated and non-hyperactivated spermatozoa. Bovine serum albumin prevented and reversed the alpha-lactalbumin-induced suppression of hyperactivation. Sperm zona pellucida binding was partially restored by lowering the alpha-lactalbumin concentration in the medium in which sperm were allowed to bind to the zona pellucida. The results suggest that mouse sperm are decapacitated by bovine mammary alpha-lactalbumin. The counteracting effect of bovine serum albumin to the suppressive action of alpha-lactalbumin on the flagellum suggests the involvement of a mechanism different from the action of alpha-lactalbumin on the sperm head inhibiting binding to the zona pellucida. PMID- 2591860 TI - Development of a noninvasive ultramicrofluorometric method for measuring net uptake of glutamine by single preimplantation mouse embryos. AB - A noninvasive ultramicrofluorometric method for measuring net uptake of glutamine by single preimplantation mouse embryos is described. A linear relationship was found between fluorescence intensity of NADH produced and glutamine concentration (R2 = 0.985). Single embryos were placed in 20 nl drops of medium containing 0.5 mM glutamine, and the medium was sampled after 2 hr incubation at 37 degrees C. Changes in net glutamine uptake were determined in one-cell, two-cell, and eight cell embryos and blastocysts incubated in medium containing no energy substrates (glucose, pyruvate, and lactate). The median glutamine uptake increased significantly from 0.480 and 0.270 pmoles/embryo/2 hr at the one-cell and two cell stages, respectively, to 1.610 pmoles/embryo/2 hr at the blastocyst stage. Mean glutamine uptake was compared in the presence or absence of energy substrates at several developmental stages. A highly significant reduction of glutamine uptake in the presence of substrates was observed at the one-cell and two-cell stages of development. At the eight-cell stage, glutamine uptake was only marginally reduced in the presence of substrates, and no effect was found at the blastocyst stage. These data may partially explain the beneficial effect of glutamine on the culture of early mouse embryos through the two-cell block of development. PMID- 2591861 TI - Lectin binding characteristics of mouse epididymal fluid and sperm extracts. AB - Glycoproteins from luminal fluid of the mouse cauda epididymidis have been compared with glycoproteins from Triton X-100 extracts of mouse spermatozoa from varying regions of the epididymis, using lectins with specific affinity for different sugar residues. Concanavalin A recognizes 11 glycocomponents on Western blots of fractionated caudal fluid; wheat germ agglutinin (WGA) binds 12 proteins; Ulex europaeus agglutinin (UEA) binds seven; and Dolichos biflorus agglutinin (DBA) recognizes nine. Several of these glycoproteins display an affinity for more than one lectin, indicating a diversity in their exposed carbohydrate residues; whereas other proteins bind only one of the four lectins used. The results also show that some glycoproteins exhibit a higher affinity for particular lectins. Eight glycoproteins of similar mobility and lectin-binding characteristics are detected in Triton X-100 extracts of spermatozoa from different regions of the epididymis and in caudal fluid. The lectin affinity of some proteins appears or increases in spermatozoa from distal epididymal regions (54 kD, 32 kD), whereas the lectin affinity of others decreases (29 kD, 40 kD). There are differences in lectin affinities between proteins in sperm extracts and in caudal fluid. Some proteins show an affinity for three or four lectins in caudal fluid, but proteins of similar electrophoretic mobility in sperm extracts bind only one or two of the lectins. These data show that glycoproteins of similar mobility are present in caudal fluid and in Triton-X-100 sperm extracts, implying a potential interaction between caudal fluid components and epididymal sperm. PMID- 2591862 TI - Changes in the rat sperm head during epididymal transit. AB - Morphological changes in sperm are one aspect of a maturation process during epididymal transit in mammals. The literature mentions only, for different strains of rats, a remodeling and decrease in size of the acrosome. In the present work, the sperm were obtained from caput, corpus, and cauda epididymis of the albino rat. Samples were processed for scanning electron microscopy, with routine techniques, and for light microscopy and video microscopy. It appeared, with these techniques, that the acrosomal curvature and the whole head surface area of the rat sperm decrease during the epididymal transit. To measure these changes, a geometrical method was designed, and surface measurements were made using a computer program. It was found that the caput sperm head has the greatest surface area and a sharper acrosome bend than the cauda sperm. In an attempt to explain the above-mentioned changes, the suggestion is offered that some compactation of the nucleus and acrosomal material could be related to the decrease of the surface area. PMID- 2591863 TI - Ultrastructural observations on gamete interactions using micromanipulated mouse oocytes. AB - Cumulus-free mouse oocytes were subjected to zona opening by cracking with microhooks (ZC) or acid drilling (ZD) and fixed 30-90 min after insemination (10(5) pre-capacitated motile sperms/ml). Ultrastructural observations were made on serially thin-sectioned oocytes: 15 ZC and 12 ZD. The zona lesion in ZC oocytes was a clean cut, whereas in ZD oocytes it formed a patchy area of partial zona loss, with reduced microvillar height on the underlying oocyte surface. Spermatozoa were observed within the perivitelline space and partially fusing with the oocyte after 30 min in both situations. Only acrosome-reacted sperm heads were observed to fuse: acrosome intact forms were generally in contact with the zona pellucida, either with the inner or outer surface. Acrosome-intact spermatozoa were also observed deeply embedded in the zona matrix, possibly indicating surface enzyme activity preceding the membrane fusion events of the acrosome reaction proper. The observations are consistent with the need for spermatozoa to make contact preferentially with the zona pellucida during the course of the acrosome reaction. PMID- 2591864 TI - Transformation of sperm nuclei into male pronuclei in nucleate and anucleate fragments of parthenogenetic mouse eggs. AB - Our objective was to examine the ability of nucleate and anucleate fragments of artificially activated mouse eggs to transform sperm nucleus into male pronucleus. To this end, zona-free oocytes in metaphase II were activated by ethanol and bisected into halves (one with the spindle, the other anucleate) either within 10 to 20 min (series A) or 3 or 5 hr later (series B). In series A, the fragments were inseminated 3.5, and 8 h after activation, and in series B, 3 and 5 h after activation. Both nucleate and anucleate fragments lose the capability of transforming sperm nucleus into fully formed pronucleus sometime between 3 and 5 h after activation. In 8 h old parthenogenetic fragments, the majority of sperm nuclei remain unchanged or begin decondensation but never reach the stage of an early pronucleus. In over 1/3 of anucleate fragments of this age group, sperm nuclei develop defectively; chromatin decondenses inside the persisting nuclear envelope. In other experimental groups, the incidence of these abnormal sperm nuclei varies between 0 and 10%. In general, the anucleate fragments retain the capability to transform sperm nuclei (fully or partially) longer than their nuclear counterparts. This difference may be accounted for by a different level of substances required for pronuclear growth (extrachromosomal constituents of the germinal vesicle and nuclear lamins): high and constant in the cytoplasm of anucleate egg halves and low and progressively decreasing in the nucleate halves because of their putative uptake by the female pronucleus. However, the cytoplasmic factors responsible for the initial stages of transformation (nuclear envelope breakdown, chromatin decondensation) become eventually inactivated both in the presence and in the absence of a female pronucleus. PMID- 2591865 TI - In vitro capacitation of boar ejaculated spermatozoa: effect of conditioned media prepared from preincubated sperm suspension. AB - The fertilizing ability of boar ejaculated spermatozoa was examined in vitro after preincubation at a concentration of 2.5 x 10(8)/ml for 4 hr in several conditioned media (CM). For preparation of CM, boar spermatozoa were incubated in a modified Krebs-Ringer bicarbonate solution (TYH) at concentrations of 20 to 40 x 10(8)/ml for several hours up to 4 hr; then their supernatant fluids were collected by centrifugation. When boar ejaculated spermatozoa were preincubated in TYH alone, 14.1% of oocytes were penetrated by them as we reported previously. On the other hand, preincubating them with CM, their fertilizing ability was elevated according as the incubation time of CM preparation was lengthened. The fertilization rate reached 75.0%, using 4 hr-incubated CM for the preincubation medium. The effect of CM was not deteriorated by heat treatments (56 degrees C, 30 min, or 100 degrees C, 5 min). The components of CM were separated at a molecular weight of 25,000 by ultrafiltration, and high fertilization rate (69.8%) was obtained when low molecular weight fraction was used for the preincubation medium. Sperm extracts prepared from directly frozen-thawed sperm suspension and 0.1-10 mM of taurine or hypotaurine had no effect on the fertilizing ability of boar spermatozoa. These results suggest that substances stimulating boar sperm capacitation were accumulated from viable spermatozoa into the medium during incubation and that the effective substances were heat-stable and of low molecular weight and were not taurine and hypotaurine. PMID- 2591866 TI - [Progress in image diagnosis: MRI]. PMID- 2591867 TI - [Progress in image diagnosis: CT]. PMID- 2591868 TI - [Progress in radionuclide imaging]. PMID- 2591869 TI - [Abdominal angiography and therapy]. PMID- 2591870 TI - [Age-related changes of immune reactivities and antitumor effects in spontaneously hypertensive rats (SHR) with T-cell depression]. AB - We investigated the relationship between age-related changes in immune responses and antitumor effects using a spontaneously hypertensive rat (SHR). The SHR shows a progressive decline of the number of thymocytes and T-cell functions as a result of aging after 2 months of age. The growth of a highly antigenic fibrosarcoma SMT-6 was significantly suppressed in SHR rats aged 1 and 2 months, whereas in SHR rats aged 6 or older no suppression was observed. On the other hand, the growth of a weakly antigenic mammary adenocarcinoma SST-2 was significantly suppressed in SHR rats aged 2 and 3 months, whereas in SHR rats aged 1 or 8 months no suppression was observed. We found that the kinetics of natural killer cell activity during the aging processes run parallel to the suppressing function of the SST-2 tumor growth. Moreover, the treatment of SHR rats with anti-asialo GM1 antiserum abrogated the suppressing function of SST-2 tumor growth in SHR rats aged 3 months. Finally, it became clear that, the treatment with Neurotropin, a natural killer activator, significantly suppressed the SST-2 tumor growth in the treated SHR rats aged 3 months when compared to non treated age-matched control. These results suggest that the growth of a low antigenic tumor such as SST-2 can be controlled by activated natural killer cells, even though, owing to aging, it is difficult for the T-cell mediated immune systems to recognize weakly antigenic or nonantigenic tumors in the state of T-cell suppression. PMID- 2591871 TI - Basic studies on the objective evaluation method of noise using the anchor effect. AB - Current objective methods that estimate noise have a defect in that the measurement values are not stable and the noise can be measured only at pre- and post-exposure times. Some previous studies on the "anchor effect" suggested that noise can be objectively evaluated by evoked potentials (N1 and P2 components), when the noise exposure and the test stimuli to elicit the evoked potentials are given alternately. However, several basic experiments are required to establish this method for noise estimation. The differences in the time durations of stimuli be interchanged with the load of noise were studied in Experiment 1. As a result only N1 latency showed significant differences. This suggested that a continuous tone is suitable for intervening stimuli. In Experiment 2, the relation between evoked potentials and differences in the frequencies of intervening and test stimuli were studied in the wide frequency ranges of 250, 500, 1k, 2k, 4k, and 8k Hz. The results showed a tendency for the frequencies of intervening stimuli to become farther and farther removed from those of the test stimuli as the N1-P2 amplitudes of the latter become larger. This result revealed that pure tones are not suitable for test stimuli; therefore, white noise and pink noise were used as test stimuli in Experiment 3. The amplitude of response induced by white noise was not changed by the frequencies of the intervening stimulus. These results suggested that using evoked potential can be an objective method for noise estimation, when white noise is loaded as a test stimulus after the intervening stimulus. PMID- 2591872 TI - [Influences of respiratory frequency on breathing mechanics during artificial ventilation in man and animal]. AB - Effects of respiratory frequency on breathing mechanics were examined on 11 surgical patients during artificial ventilation with inhalation of nitrous oxide, oxygen and halothane (GOF). When the respiratory frequency was increased stepwise from 10 to 30/min, the total compliance was significantly reduced stepwise (from 55.42 +/- 9.55 ml/cmH2O to 47.38 +/- 9.31, p less than 0.01). In animal experiment, the respiratory frequency was similarly increased from 10 to 30/min in 11 mongrel dogs under sodium thiamylal anesthesia with air breathing. The total pulmonary compliance decreased significantly from a control level of 13.62 +/- 5.04 ml/cmH2O to a value of 10.96 +/- 3.00 ml/cmH2O which was obtained under the administration of synthetic histamine (betazole hydrochloride) (p less than 0.01). However, the decreases in compliance with histamine were parallel with the control values without the drug treatment. From these results it was assumed that the reduction of the total pulmonary compliance under increased respiratory frequency was due not to changes in small airway but to those in large airway. PMID- 2591873 TI - [Prolonged preservation of isolated canine hearts: evaluation by measuring myocardial energy charge]. AB - Since no appropriate system has been established for the transportation of donor hearts in japan, the establishment of successful techniques for their preservation of a longer period is necessary for heart transplantation. The purpose of this study is to assess energy charge as a parameter of the viability in the prolonged heart preservation. Hearts from ten mongrel dogs were excised after being flushed with cold Young's solution and were perfused with LV vent for 24 or 48 hours at 30 cm H2O. The composition of the perfusate was K+40, Mg2+26 mEq/L, and the pH was controlled around 7.5 and the temperature 4-7 degrees C. After Langendorff's perfusion for forty minutes, five hearts were reperfused at 31 degrees C in a circuit using an organic filter, and were evaluated for hemodynamic parameters. Four hearts which were preserved for 48 hours had poor results, however one heart preserved for 24 hours showed very good hemodynamic data equivalent to those from hearts immediately after excision. In metabolic studies from another five cases myocardial energy charge retained the value above 0.8 for 40 hours, although myocardial adenosine triphosphates gradually diminished; however, both decreased rapidly after 40 hours. Considering that the energy charge represents real viability of myocardium, together with the changes in pH, etc., it is suggested that this method can safely preserve the isolated hearts up to 40 hours. PMID- 2591874 TI - [Lymphatic and vascular systems of the gallbladder--with special reference to carcinoma of the gallbladder]. AB - To understand the spreading modes of cancer of the gallbladder concerning its surgical treatment, relation between the infiltration depth of the cancer and the lymph and blood vessel systems in the gallbladder was investigated. Clinico pathological studies of 23 cases of the gallbladder carcinoma showed that the infiltration depth related to the degree of differentiation, invasiveness to lymph and blood vessel, and the metastasis of lymph nodes. Lymphatic and vascular systems of the gallbladder and bile duct were examined in 22 dogs. The vasculature in the wall of the gallbladder was divided into three layers. The veins at the liver bed were communicated with the intrahepatic portal veins. The lymphatic system in the wall was more clearly shown after obstruction of lymph vessels by ligation of soft tissues in the hepatoduodenal ligament and revealed four layers. The lymph vessels draining from the gallbladder descended along the cystic duct and the bile duct. They passed the portal and pancreatoduodenal lymph nodes and entered the cisterna chyli. In addition, lymph obstruction revealed other lymph tracts to the hepatic parenchyma of the hepatic hilum, retroperitoneum, celiac axis and the splenic vessel regions. The findings suggest that (1) simple cholecystectomy is suitable for the intramucosal carcinoma. (2) for the carcinoma infiltrating to the lamina muscularis, vascular invasion and spreading to the liver through the liver bed of gallbladder is suspected, and (3) for the carcinoma with subserosal infiltration, hepatic segmentectomy with complete resection of the extrahepatic bile duct and removal of the regional lymph nodes of the hepatoduodenal ligament and the vicinity of the gastropancreatic region are required because vascular and lymphatic spreads are suspected. Adjuvant therapy should be required and strict follow up survey should be maintained. PMID- 2591875 TI - [Experimental analysis of postoperative early recurrence of liver cancer]. AB - The author suspected that the high incidence of early recurrence after macroscopically curative operation in human liver cancers correlated with the production of liver regeneration factor which was induced following partial hepatectomy (PH). The author therefore analyzed whether PH enhanced the growth of liver cancers or not, and the relevant mechanism involved, using rats subcutaneously injected with hepatocellular carcinoma (KDH-8, AH-66) cells. Primarily, it proved that PH significantly enhanced the growth of liver cancers injected in rats. The effect of this enhancement of liver cancer growth appeared as an abrupt increase in tumor volume within 24 hours following PH, which fact was supported by the mitotic indices of the hepatocellular carcinoma (KDH-8) cells. However PH did not affect rats injected with mammary carcinoma (SST-2) cells without estrogen receptor (E2R) or fibrosarcoma (KMT-75) cells. Secondly, based on this result, the author tried to analyze the mechanism of enhanced growth of liver cancers following PH, from the standpoints of; changes in postoperative immunity, expression of cytosol E2R in liver cancer cells or liver regeneration factor, using KDH-8 cells. The changes in postoperative immunity (NK activity and Blastogenesis) did not correlate with the changes in liver cancer growth. Although serum estradiol (E2) increased significantly after PH, E2R was not detected in the KDH-8 cells used in this experiment. Serum was obtained from healthy rats 24 hours after PH, and 20 mg of serum, as calculated from total protein, was eluted into 50 fractions by high liquid chromatography (column; TSK G3000 SW). When the author examined which fractions stimulated both the growth of primarily cultivated hepatocytes and KDH-8 cells, only the fraction Fr. 30, the molecular weight of which was about 100 Kd, enhanced both. Furthermore, the author performed an in vivo assay to determine the number of days needed for tumor appearance: PHs were carried out 2 months, 5 days and 1 day before, at the same day of, and 1 day and 5 days after KDH-8 cell (500 cells/100 microliters, sc) inoculation. The author also noticed from these in vivo tests that PHs which were performed 1 day before, at the same day of, and 1 day and 5 days after the KDH-8 cell inoculation enhanced significantly the growth of liver cancers. PMID- 2591876 TI - [Carpal tunnel syndrome in acromegaly--4-case report and review of literature]. AB - Four cases of carpal tunnel syndrome in acromegaly were reported. These 4 cases were found in 21 acromegalies (19%). Besides change of features, they complained bilateral sensory disturbances of their hands. After transsphenoidal removal of pituitary adenoma, GH levels returned to the normal range and sensory disturbances were improved in all cases. Mechanism of carpal tunnel syndrome in acromegaly is that edematous synovial tissues compress the median nerve because oversecretion of growth hormone causes increase of sodium and water retention in the extracellular fluid. The patient who showes high basal level of growth hormone and/or acromegalic pattern by various tolerance tests does not always have the carpal tunnel syndrome. But this syndrome is apt to be found in active acromegaly. So the detection of the symptom showed by this activity such as hypersudation in our cases leads to the early diagnosis of acromegaly. PMID- 2591877 TI - [Studies on the development and growth of the human maxilla--special references to the anterolateral, infratemporal and orbital surfaces]. AB - Morphological and macroscopical studies were made on the lateral surface of the human maxilla. The materials consist of 128 cases of human fetuses ranging from the fourth to the tenth month and 306 cases of human juveniles and adults. The earliest month in which the loci with the scientific name (Nomina Anatomica) of the maxilla was observed was as follows; the frontal process, zygomatic process, anterior nasal spine and the nasal notch were first observed on the fourth fetal month. The infraorbital foramen and anterior lacrimal crest were first observed in some cases on the fourth fetal month and in all cases on the fifth fetal month. The infraorbital suture, lacrimal notch and alveolar process were first observed on the fifth to the sixth fetal month. The infraorbital sulcus and infraorbital canal were first formed on the fifth to the seventh fetal month. The following loci on the lateral surface of the maxilla which are related to the development of the maxillary teeth were first observed after birth as follows; the alveolar foramina were first observed in 3 to 7 years after birth and the maxillary tuberosity was first observed in 6 to 7 years after birth. The canine fossa was first observed in 6 years after birth. As far as the development of the maxilla is concerned, the frontal process and infraorbital margin were first observed and secondly the alveolar part was observed and finally the maxilla body which involved the maxillary sinus was formed. PMID- 2591878 TI - Effects of a high lipidic diet on murine energetic reserves in food deprivation. AB - Female mice were fed for one month either control or cafeteria diets. Then they were subjected to food deprivation for up to 36 hours and their weight loss, tissue lipid, glycogen and protein were determined together with their plasma glycose, amino acids, urea, lipoproteins and ketone bodies. Cafeteria mice were able to cope with prolonged starvation with altered plasma composition and important loss of lipids and protein, sparing to a certain degree their glucose and amino acids. Control-fed mice, however, showed a intense ketosis and significant losses of nitrogen. The results obtained showed a higher ability of cafeteria mice to handle and use lipids, that evolves in a better suitability to resist food deprivation with less extensive alterations in their fuel and nitrogen homeostasis. PMID- 2591879 TI - Comparison of effects of verapamil, low calcium diet and betamethasone on duodenal calcium absorption efficiency in the chick. AB - The results indicate that oral administration of verapamil for 2 weeks to the chick is followed by an increase in the efficiency of the duodenal absorption of calcium. In these chicks both a decrease in serum calcium level and an increase in the activity of renal 1 alpha-hydroxylase were observed. The increased calcium absorption following prolonged treatment with verapamil resembles that induced by a low calcium diet. The mechanism of both responses presumably involves an increased production of 1,25-dihydroxyvitamin D3. Both verapamil- and low calcium diet-induced adaptations are capable of overcoming the inhibitory action of betamethasone on intestinal calcium absorption. No effects on calcium absorption were noted if verapamil was administered intraperitoneally which suggests that verapamil exerts its action directly on the intestinal mucosa. PMID- 2591881 TI - Increased brown adipose tissue activity in children with malignant disease. PMID- 2591882 TI - Who profits from deinstitutionalization? PMID- 2591883 TI - The dollar cost of patient assault. PMID- 2591880 TI - The response to isoproterenol-stimulated adenylate cyclase activity after administration of L-triiodothyronine is reduced in aged rats. PMID- 2591884 TI - Families' experiences in psychiatric emergencies. AB - Sixty families from three self-help, psychoeducational groups in western New York State were interviewed about their experiences during recent psychiatric emergencies involving their mentally ill relatives. Twenty-six hospital-based emergency mental health service providers were compared with the families on key attitudes toward emergency services. Families reported that emergencies were complicated and traumatic and that they involved contacts with numerous agencies, sometimes over several months. Satisfaction with the emergency service system was generally low among both families and hospital service providers. Service providers were less likely than families to believe that families' assessments of their ill relatives' need for treatment were credible. The author suggests that apparently "crazy" behavior of families may make sense in the context of serious patient pathology and a general lack of emergency assistance. Much effort is needed to develop coordinated emergency mental health treatment that is sensitive to families' needs. PMID- 2591885 TI - Diagnostic consultation to a state hospital. AB - As part of a program to assess the needs of patients in a state hospital scheduled to be closed, a psychiatrist provided consultation for 101 chronically ill patients, including formulation of a principal diagnosis by DSM-III-R criteria. Compared with earlier diagnoses made by the hospital, the consultant diagnosed fewer cases of schizophrenia and more cases of organic mental disorders, affective syndromes, and mental retardation and pervasive developmental disorders. The largest numbers of patients no longer diagnosed as schizophrenic received diagnoses of psychosis not otherwise specified, with further assessment recommended, or organic mental disorder. The author believes consultation programs like this one can help state hospital staff take a fresh look at long-term patients and can provide useful experience for psychiatric residents who assist with such consultations. PMID- 2591886 TI - Short-term psychopathology in eyewitnesses to mass murder. PMID- 2591887 TI - Characteristics and behavior of patients involved in psychiatric ward incidents. PMID- 2591888 TI - Social support for caretakers and psychiatric rehospitalization. PMID- 2591889 TI - Smoking control in a psychiatric setting. PMID- 2591890 TI - Let the patient smoke. PMID- 2591891 TI - Women and firearms. PMID- 2591892 TI - Errors in arrest rates. PMID- 2591893 TI - Funding in California. PMID- 2591894 TI - FDA approves clozapine for treatment of schizophrenia; careful monitoring required. PMID- 2591896 TI - Quality awareness pervades hospitals in '89. PMID- 2591897 TI - Hot in 1989: friendly physicians, loyalty. PMID- 2591895 TI - Hospital finances stable, but remain critical. PMID- 2591898 TI - Biotechnology, cost concerns dominate in 1989. PMID- 2591899 TI - Alliances: changing focus for changing times. AB - Alliance networks were supposed to offer members the same buying clout enjoyed by national health care systems and the opportunity to contract with employers as part of a national health care delivery network. But overly optimistic projections about how quickly alliances could reach those goals--and what it would cost to teach them--led to unmanaged growth and disgruntled members. According to our cover story, alliances now are adjusting to changing conditions by adopting strategies to serve the needs of hospitals and systems competing in regional markets. PMID- 2591900 TI - Accountability is still key word in marketing. PMID- 2591901 TI - Experts: staffing, compensation problems continue. PMID- 2591902 TI - Moves to standardize, monitor practice mark '89. PMID- 2591903 TI - Rate hikes slow HMO growth, but not forever. PMID- 2591904 TI - Hospitals look for savings in unusual places. PMID- 2591906 TI - Medical malpractice rates decreased in 1989. PMID- 2591907 TI - Outpatient and emergency care center of '89 action. PMID- 2591905 TI - National health insurance gains new ally: business. PMID- 2591909 TI - Occupational health must meet companies' needs. PMID- 2591908 TI - Hospital CEO positions: not enough to go around. PMID- 2591910 TI - Genetic structure of Mennonite populations of Kansas and Nebraska. AB - We describe the gene frequency distributions for 29 different blood group, serum, and erythrocytic proteins for three Mennonite communities from Kansas and Nebraska and compare their gene frequencies with those of Amish, Hutterite, and Mennonite populations using the topological method of Harpending and Jenkins (1973). Subdivision of these communities into congregations reveals that the "fission-fusion'h model best characterizes the relationship between the genetic patterns and historical events. These Mennonite populations, although reproductively isolated at the turn of this century, are presently entering the mainstream of US rural culture. PMID- 2591912 TI - Human enzyme polymorphism in the Canary Islands. III. Tenerife Island population. AB - We analyzed the genetic polymorphism of eight red cell enzymes in samples from different geographical areas of Tenerife and the Iberian peninsula. The gene frequency heterogeneity found within the Tenerife samples was at the same level as that of Tenerife-mainland comparisons. The presence of the Negroid G6PD A+ allele in the Tenerife samples is evidence of an African admixture with a mean estimation of 4.5%. PMID- 2591913 TI - Heritability of quantitative orbital traits. AB - We conducted a study of 63 couples and their 242 normal children from northeastern Brazil (no facial malformations or deformities) to evaluate the heritability of 4 quantitative traits of the orbital region adjusted by covariance for sex, age, (age)2, sex x age, and sex x (age)2. The heritability is estimated as 0.514 for the mean horizontal diameter of the palpebral fissures, 0.454 for the interpupillary distance, 0.390 for the internal intercanthal distance, and 0.337 for the external intercanthal distance. The heritability of the first principal component of the orbital region is estimated as 0.418. PMID- 2591911 TI - Voluntary and electrically evoked strength characteristics of obese and nonobese preadolescent boys. AB - Overweight and obese children demonstrate inferior motor performance for strength and power-related activities requiring support or lifting of body weight. Our purpose here was to determine whether the inferior performance could be attributed to a lower strength to muscle area ratio in the obese. Eleven nonobese (16.6% fat) and 13 obese (35.5% fat) boys (9-13 years old) volunteered for the study. Peak torque was measured during voluntary isometric and isokinetic elbow flexion and knee extension at four joint angles and four velocities, respectively. The contractile properties, twitch torque, time to peak torque, and half-relaxation time were evoked for the elbow flexors by percutaneous stimulation. Elbow flexor and knee extensor cross-sectional areas (CSA) were determined by computed axial tomography taken at the mid-upper arm and mid-thigh, respectively. Isometric and isokinetic elbow flexion and knee extension strength normalized for body weight were significantly (p less than 0.05) higher in the nonobese compared to the obese boys. There were no significant (p greater than 0.05) differences, however, between groups for elbow flexor and knee extensor CSA or for absolute and relative (normalized for muscle CSA or the product of muscle CSA and height, the latter accounting for differences in moment arm length) isometric, isokinetic, or evoked twitch torque for elbow flexion or knee extension. Likewise, there were no differences between groups for the time related contractile properties, time to peak torque, or half-relaxation time. These findings suggest that there is no difference in the intrinsic strength or contractile properties of the elbow flexor and knee extensor muscles between obese and nonobese pre-adolescent boys and that other factors, such as the handicapping effect of excess fat mass, probably account for the reduced motor performance of the obese child. PMID- 2591914 TI - Effect of endurance training on gross energy expenditure during exercise. AB - We compared the effect of endurance exercise training on gross energy expenditure (GEE) during steady-state exercise in 20 younger men (31.2 +/- 0.6 years) and 20 middle-aged men (49.2 +/- 1.1 years). The subjects trained for eight months. The training program consisted of three 45-min walking and jogging exercise sessions per week at an intensity of approximately 60-85% of the heart rate at peak VO2. We administered bicycle ergometer tests at 0, 4, and 8 months into training. Participants exercised at a power output of 100 W for 10 min using a pedaling frequency of 50 rpm. We determined GEE (kcal/min) by measuring the oxygen consumption and respiratory exchange ratio. We found a significant reduction (p less than 0.05) in GEE (0.7-1.3 kcal/min) following 4 months of endurance training in both age groups, with a further reduction (p less than 0.05) noted in only the middle-aged group at month 8. We found no difference (p greater than 0.05) in GEE between the younger and middle-aged men. We conclude that chronic exercise may modify GEE during a submaximal exercise bout and that this adaptation is similar in magnitude in younger and middle-aged men. PMID- 2591915 TI - Seasonality of births: stability and change in a developing country. AB - A marked seasonality of births for the two main ethnic groups of peninsular Malaysia, far exceeding the cyclic fluctuations in births in the United States and Canada, was reported for the 1960s. A 36% excess of births over the average monthly number was observed among Malays each January. Among the ethnic Chinese in Malaysia a regular periodicity in the numbers of births was also found, but it was far less marked and the peak occurred in October or November. The peaks in both groups were due in large measure to conceptions that correlate with religious observances or holidays. Here I report on cyclic birth patterns in peninsular Malaysia for the period 1970-1985. Rapid economic development has occurred during this time and has brought with it demographic changes, such as a massive rise in contraceptive use and a decline in birth rates. These demographic changes have been accompanied by the loss of the pronounced seasonal pattern of births among the Malays. The seasonality of Malay births is now of roughly the same magnitude as the seasonality in the United States and Canada, whereas seasonality of births among the Chinese in Malaysia remains essentially unchanged. PMID- 2591916 TI - Conceptive delays of twin-prone mothers: a demographic epidemiologic approach. AB - We studied the time interval to the first birth and to the twin birth using statistical and mathematical models in two groups of mothers, those with twins and those with singletons, from the same population. We made use of a pair matched case-control design. We treated the maternal birth cohort and parity as confounders and thus as controlled. We also investigated the sex of twin pairs as an interactive variable, employing such methods as survival curve testing and using geometric, gamma, and exponential distributions where appropriate. The expectations derived from the mathematical models yield numerical estimates of fertility components. The results suggest that unlike-sex twin-prone mothers have higher fecundity than controls when they conceive singletons. Further, fecundity appears high and unimpaired before the birth of twins. Mothers of like-sex twins experience somewhat shorter and but more variable birth intervals than corresponding controls before the birth of twins, suggesting within-group heterogeneity. Specifically, the birth of like-sex twins is preceded by low fecundity and a short period of postpartum amenorrhea. Biologically, like-sex (presumably monozygotic) twin-prone mothers have a hormonal defect related eventually to menopausal status that interferes with ovulation and perhaps with lactation. As for unlike-sex twin-bearing mothers, they probably experience a displacement of their maximum fertility potential toward early reproductive life and an extension of their menstrual life. From a methodologic standpoint, the study of the fertility of twin-prone mothers cannot proceed without estimates of the fertility components of birth intervals, as these intervals do not lend themselves to straightforward analytical interpretations by statistical analyses. PMID- 2591917 TI - [Endocytosis and cytotoxin effect induced by the attachment of the glycolipoprotein of leptospires to vascular endothelial cell in culture]. AB - The Glycolipoprotein (GLP) of various virulent leptospires was extracted, purified and identified. The GLP was combined with fluorescence rhodamine B and the colloidal gold as the probe. Meanwhile, the bovine aortic endothelial cell (EN) was isolated and cultured in the medium 199 "Nissui". The GLP-rhodamine B and GLP-colloidal gold probe were added to cultured EN and incubated at 4 degrees C for 2 h then at 37 degrees C for 2 h. The interaction between GLP-rhodamine B, GLP-CG probe and EN were observed and photography by fluorescence microscopy (Leitz) and scanning electronmicroscopy. The releasing rate of lactic acid dehydrogenase (LDH), acid phosphatase (AcP) and protein from the EN were detected. The results indicated that the GLP of Leptospira interrogans serovar Lai, strain 017 attached to EN and a endocytosis was happened subsequently. The LDH and AcP releasing rate were significantly higher than control and the cell protein was much less than control. The results showed that the GLP of L. interrogans strain 017 had the cytotoxin effect through a specific attachment, endocytosis in EN. The endocytosis probably is a receptor-mediated endocytosis. PMID- 2591918 TI - [Thymus pathological changes in perinatal babies and children]. AB - The most outstanding pathological changes of perinatal babies and children, based on the review of the autopsy files in the 1st Affiliated Hospital of West China University of Medical Sciences, are lymphocytic depletion, and reticuloepithelial cell swelling and/or fusiform malformation in the cortex, while in the medulla apoptosis is more prominent. We suppose that these alterations are due to immaturity of cortical thymocytes, and in the diseased condition, they are easily affected by extraordinary factors, especially the influence of corticosterone inducing acute severe necrosis, so the number of lymphocytes are obviously diminished. But, in the medulla, as intact mature lymphocytes exist, physiological phenomenon such as apoptosis is rather prominent in it. While in the medulla, Hassall's corpuscles have various characteristic changes, such as cornification, calcification, fusion, cystic change and disintegration. Besides, we observed a new alteration in the thymus defined as vacuolization. All the above pathological changes reached the peak in the 28- day group; there after, they might become either worse or better according to the condition of the disease and growth of the body. However, these are still problems to be further studied separately. PMID- 2591920 TI - [Development and application of hybridoma secreting monoclonal antibody against poly-human serum albumin]. AB - Two hybridomas which secrete monoclonal antibody (McAb) against polymerized human serum albumin (PHSA) were obtained by the fusion of SP2/0 myeloma cell with immune murine spleen cells. One of the McAb was identified as mouse IgG1, the other was IgM. The titers of these purified McAb was 1:16 364 with passive hemagglutination assay (PHA). After labelling with 125I by chloramine-T method, a solid phase radioimmune assay for detecting the PHSA has yielded in 21 positive results, out of 126 HBsAg positive sera, but 53 HBsAg negative sera were all negative. At present we have not seen any report of PHSA present in circulation. PHSA may be as a bridge bind receptor between HBV and hepatocytes and then initiate infection. The appearance of PHSA in HBsAg positive sera could be the result of the damage of the liver during virus infection. More work should be done for this explanation. PMID- 2591919 TI - [Intraoperative hemodynamics of pyrolytic carbon cambered bileaflet valve replacement in animals]. AB - Pyrolytic carbon cambered bileaflet valve developed by Chengdu University of Technology and Sciences was evaluated for its hemodynamics. The curved surface of the valve leaflet is cylindrical. Under anaesthesia, cardiopulmonary bypass and chemical cardioplegia, a cambered bileaflet valve (i.d. = 16 mm) was replaced at mitral position in each of 12 goats. Before valve replacement, mitral flow rate (MFR) was 74.9 +/- 12.3 ml.sec-1, average valvular pressure drop delta P) 0.56 +/ 0.17 kPa (4.2 +/- 1.3 mmHg) and effective opening area (EOA) of the valve 1.20 +/- 0.18 cm2. After valve replacement, corresponding hemodynamic parameters were 49.3 +/- 12.7 ml.sec-1, 0.46 +/- 0.17 kPa (3.8 +/- 1.3 mmHg) and 0.81 +/- 0.12 cm2 respectively. In our previous report on yak pericardiac heart valve (i.d. = 20 mm) in goats, corresponding hemodynamic parameters after valve replacement were 45.6 +/- 11.8 ml.sec-1, 0.86 +/- 0.32 kpa (6.4 +/- 2.4 mmHg) and 0.65 +/- 0.26 cm2. With comparable mitral flow rate and heart rate (113.6 +/- 19.6 min-1 vs 119.1 +/- 17.1 min-1), the average valvular pressure drop of pyrolytic carbon cambered bileaflet valve is significantly smaller than that of the yak pericardiac valve (P less than 0.001), and the effective opening area is marginally larger than that of the yak pericardiac valve (0.05 less than P less than 0.1). If the same-sized valves of this two kinds are used, the hemodynamic parameter of cambered bileaflet valve would be better than those of yak pericardiac valve. Since the latter valve has been successfully used in patients, the present valve might be applicable in clinical situation. PMID- 2591921 TI - [A preliminary study on immune complexes in myasthenia gravis]. AB - The levels of circulating immune complex from 43 patients with myasthenia gravis (MG) and 50 normal controls were detected by using ELISA based on bovine conglutinin. The levels of circulating immune complex in MG patients were higher than those in normal controls (P less than 0.01). Although the levels of circulating immune complex in generalized type MG were higher than those in ocular type MG, the difference showed no statistically significant. It was found that the levels of circulating immune complex, both generalized type MG and ocular type MG, were higher than those in normal controls respectively (P less than 0.01). PMID- 2591923 TI - [Quantitation of human serum apolipoprotein E by Rocket immuno-electrophoresis]. AB - Apo E was purified from the very low density lipoprotein (VLDL) of normal and hypertriglyceridemic subjects by Sephadex G-75, heparin-Sepharose 4B affinity chromatography, and preparative SDS polyacrylamide gel electrophoresis. The antisera were produced by injecting apo E into goats. With apo E antisera, Rocket immuno-electrophoretic method was developed to quantitate apo E levels in normal and hypertriglyceridemic human serum. The detection limit was 5.5 ng apo E. The coefficients of variation of intra- and interassay were 2.6% and 5.2%, respectively. The serum apo E level of 50 normal lipodemic subjects in Chengdu area was 4.7 +/- 1.2 mg/dl. PMID- 2591922 TI - [The pharmacokinetic study of 3H-alpha-2-butylhydroxybenzyl alcohol in rabbits]. AB - A derivative of Gastrodigenin, alpha-2-butylhydroxybenzyl alcohol, has shown a high distribution in the mice brain and stronger pharmacologic effects than its parent compounds. With 3H-alpha-2-butylhydroxybenzyl alcohol as radioactive tracer, pharmacokinetic data were obtained after the intravenous administration of a single dose alpha-2-butylhydroxybenzyl alcohol to rabbits, according to a cross-over design. Then, serial plasma samples were taken from 1 min to 480 min and measured by liquid scintillation counter. The data were analyzed by IBMPC computer for the estimation of pharmacokinetic parameters and the judgement of compartment model with a program recently developed by ourselves. The results suggested that the pharmacokinetics of alpha-2-butylhydroxybenzyl alcohol accords with the two compartment open model based on either the comparison of the calculated theoretic value with measured concentration or F test for the model judgement, and that the process of distribution was quite rapid, and the elimination half-life (T1/2 beta) was 12 h, indicating a slow elimination process. PMID- 2591925 TI - [Kinetics of solid-state decomposition of aspirin]. AB - The kinetics of the solid-state decomposition of aspirin was studied at 85 degrees, 80 degrees, 75 degrees, 70 degrees C and various relative humidities. Decomposition percentage of aspirin (x) and time (t) could be described by the equation: x = ktn where k is a constant which depends on the temperature and relative humidity. The water vapour pressure effected on the solid-state decomposition of aspirin may be presented by the Arrhenius equation: k = A.exp ( E/RT).Ps where T is the absolute temperature, P is water vapour pressure, s is a constant, R is the gas constant, A is another constant, E is the activation energy. From this equation, the activation energy of the decomposition of aspirin is calculated to be 122.17kJ.mol-1 (29.2 kcal.mol-1). PMID- 2591924 TI - [New taxa of coptis from China]. AB - The rhizomes of Coptis, known as Huang-Lian, are commonly used as traditional Chinese drugs. Two new species, viz., Coptis linearisepala, C. gulinensis and a new variety, viz., C. chinensis var. unguiculata are reported and the descriptions of the new species and new variety are presented in the present paper. PMID- 2591926 TI - [Research of the electrophysiological properties of isolated ventricular papillary muscle of rhesus]. AB - The electrophysiological properties of cardiac muscle of rhesus (Macaca mulatta) by use of intracellular electrode technique has been described in this paper. Thirty papillary muscle from 8 rhesus were used for this research and 68 successful records had been obtained. The value of resting potential is -86.26 +/ 7.57 mV (M +/- SD). The configuration of the action potential is typical for the ventricular muscle of mammalian. The amplitude of action potential is 118.80 +/- 10.69 mV: over-shoot is 25.57 +/- 6.11mV. The APD20, APD50, APD80, APD100 is 184.33 +/- 64.04, 301.02 +/- 95.32, 382.17 +/- 125.81 and 436.33 +/- 122.39 ms, respectively. The maximum depolarization velocity of 0 phase is 101.20 +/- 17.59 V/s. The effective refractory period is 292.69 +/- 93.91ms. Comparing the results of the rhesus cardiac muscle with that of other mammalians, authors found that they were very similar. It is suggested that the results and analysis of its mechanism derived from investigation of other mammalian cardiac tissues are applicable to the human. PMID- 2591927 TI - [Application of electron microscopy to tumor diagnosis--observation of 1000 cases with both light and electron microscopy]. AB - We observed 1000 cases human tumors by electron microscope, as compared with by light microscope. Results were classified into four groups: First, the diagnosis by both light microscope and electron microscope were the same in 92 per cent of total cases. Second, diagnosis by light microscope was completely changed by the use of electron microscope, and the correct diagnosis was determined only by electron microscope in 4 percent when light microscope failed. Third, although major diagnosis of some tumors by both light and electron microscope was the same, by electron microscope, the diagnosis was extended and supplemented in 3 per cent. Finally, diagnosis was still unclear in 1 per cent. We think that ultrastructural evaluation contributes to diagnosis in 7 per cent of all the cases. Electron microscope plays a very important role in the differential diagnosis of tumors, especially, small cell malignant tumors, and pleomorphic malignant tumors, and also in determination of two-directional or multi directional differentiation of some tumors. PMID- 2591928 TI - [Morphological observation on 6th-week development of human kidneys and gonads]. AB - The development of kidney and gonad of 3-6th-week human embryos were studied. Their positions at different developing stages were measured in terms of the sequence of neural ganglion according to Felix's method. The 9.5 mm embryo: Pronephrons are seen as 2 epithelial blind tubules on the right side and 1 on the left at the 6th cervical ganglion level. The lateral tubule on the right side and the left one are pronephric ducts, whereas the medial one on the right side is the pronephric tubule. The cranial ends of mesonephrons on both sides level at the 1st thoracic ganglia and run caudally to the 11th thoracic ganglia, their total number amount to 62. The mesonephric ducts on both sides firstly appear opposite to the 1st thoracic ganglia and open caudally into the cloaca. The metanephrons, the ureteric buds are unbranched yet and the metanephric mesoderm appears as clusters of cells on both sides. The gonads are indifferent. The 11 mm embryo: Pronephrons degenerated. The cranial ends of mesonephric tubules locate at the 3rd thoracic ganglia level on both sides and extend caudally to the level of the 11th ganglion in the right side and 12th in the left, their total number amounts to 65. Mesonephric ducts appear opposite to the 4th thoracic ganglia on both sides, running caudally, and open into the cloaca. Metanephrons, the ureteric buds give off 1st grade branches on both sides and metanephric mesoderm remain as clusters of cells. The gonads are indifferent. The 12 mm embryo: Pronephrons degenerated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591929 TI - [Observation and measurement of coronary arteries of goat]. AB - The coronary arteries of 50 goats were studied by means of angiography and dissection. The results were as follows: The right coronary artery (RCA) and left coronary artery (LCA) arose from the right and left aortic sinuses respectively. At the beginning, the average external diameter of RCA (2.98 +/- 1.02 mm) was smaller than that of LCA (3.42 +/- 0.74 mm). An independent inter ventricular septal artery (in 94%) supplied the upper two-thirds of the inter ventricular septum. The arterial distributive types were divided into three: The LCA was dominant in 96%, symmetrical in 4%, RCA dominant in 0%. Sixty two percent of the S-A node arteries arose from the RCA, 28% from LCA, 10% from both RCA and LCA. All the A-V node arteries originated from the LCA. PMID- 2591930 TI - [Study of Ag-NOR, SCE and micronucleus in peripheral blood lymphocyte of chromate producers]. AB - Ag-NOR, SCE and micronucleus test of peripheral blood lymphocyte obtained from 31 chromate producers had been studied. We found that (1) in the workers who had been exposed over eight years, the frequency of Ag-NOR, Ag-AA and SCE were 6.905 +/- 1.100, 0.380 +/- 0.652 and 8.190 +/- 3.727, but in the control group, 6.512 +/- 1.595, 0.215 +/- 0.529 and 7.171 +/- 2.683, respectively. So there was considerably significant difference between the exposed and the unexposed (P less than 0.01); (2) the frequency of micronuclei was 3.71 +/- 1.419% in the exposed group; however, in the control group it was 0.333 +/- 0.479%. So there was also remarkably significant difference between them (P less than 0.001). The observations lead the authors to conclude that the genetic material of the workers who have been working over eight years may be damaged because of being exposed to chromate. PMID- 2591931 TI - [Studies on the mutagenicity of amrinone and milrinone]. AB - The mutagenicity of domestic new drugs amrinone and milrinone were studied by Ames test, micronucleus test of mouse bone marrow and chromosome aberration assay in CHO cells. The results were as follows: neither amrinone nor milrinone was mutagenic in the Ames test; in chromosome aberration assay, both gave positive results; in mouse micronucleus test, amrinone gave a positive result when mice were exposed to 0.8 LD50 dose, but milrinone gave a negative result. These results suggested that amrinone and milrinone did not induce gene mutation, but amrinone induced chromosome damage both in vitro and in vivo, while the chromosome-damaging activity of milrinone in vitro may be minimized by biodetoxication in vivo. PMID- 2591932 TI - [Quantification of pulmonary to systemic flow ratio (Qp/Qs) in children with patent ductus arteriosus by echocardiography]. AB - The assessment of left-right ductal shunting flow in 35 children with PDA by 2 DCE with 35 normal children as a control was shown in the study. A close relationship was demonstrated between the grade of the diastolic negative contrast at the distal ends of the pulmonary artery and Q p/Qs. The diastolic negative contrast effect of 2-DCE could be used as a new important index in the assessment of left-to-right ductal shunting flow. Four parameters which were closely correlated with Qp/Qs were selected from 8 parameters by the stepwise multilinear regression procedure. The 4 parameters were grade II DNCE, LVPWER, grade I DNCE, LADR. A regression equation which was capable of assessing Q p/Qs noninvasively in children with PDA was derived from the 4 parameters. The accuracy of calculation of Qp/Qs by the regression equation was 80%. PMID- 2591933 TI - [Differences in length and weight growth patterns between urban and rural infants]. AB - Mixed longitudinal data of length and weight growth from 595 rural and 337 urban infants were analysed. Count models were fitted to the means of length and weight in different ages, sexes and feedings separately. The curve fitting to the data was rather satisfactory. Comparison of model parameters between urban and rural infants suggested that rural infants had a higher length level at birth but lower accelerative growth afterwards than urban ones, which was even more obvious in breast-fed infants. The difference in birth weight between them was not significant; and the urban infants had a faster linear growth velocity than rural ones. These results might be caused by the fact that food supplementing in urban infants was significantly earlier and better than in rural ones. PMID- 2591934 TI - [Influence of zinc deprivation on thymus, spleen development and adenosine deaminase activity in young rats]. AB - This study on the thymus and spleen development and ADA activity was done in young rats with zinc deprivation and supplementation. The serum zinc level, body weight, absolute and relative weight, and ADA activity of the thymus and spleen were compared between the experimental rats and the control group. Above indications were all decreased; especially both the thymus weight and the thymus ADA activity were markedly decreased in the zinc deficient group. The averages of thymic absolute weight, relative weight and ADA activity were dropped by 61.32%, 54.54% and 47.59%, respectively. After zinc supplementation for one month, all the body weight, weight of the thymus and spleen, and ADA activity of the spleen were recovered to the control group's level, while ADA activity of the thymus was 33.03% higher than that of the control group. Our data suggested that zinc was not only an important trace element in maintaining the growth of the body, the development of the thymus and spleen, but it may be an important agent to activate the ADA or to prompt synthesis of ADA. PMID- 2591935 TI - [Relationship between HBcAg in the liver and mechanisms of chronic type B hepatitis HBVM in serum]. AB - We detected the presence and distribution of HBcAg in the liver by immunohistochemistry (ABC method) and the presence of HBV-DNA in serum (spot hybridization) and anti-HBe in serum (ELISA) from 59 cases of hepatitis B hospitalized in our hospital, including 47 cases of CAH, 5 cases of CPH, and 7 cases of subacute fulminant hepatitis. 1. HBcAg in the liver was detected in 25 out of 47 cases (53%) of CAH, in 2 out of 5 cases of CPH and in 4 out of 7 cases of subacute fulminant hepatitis. The total percentage was 53% (31/59). 2. There was no positive correlation between HBV replication activity and liver disease activity (P greater than 0.05). Our results did not support the hypothesis that suggests a direct cytopathic effect of HBV. Oppositely, the fact was that the presence, the amount and the patterns of HBcAg in the liver, and the presence of HBV-DNA in serum were predominant in mild CAH compared with those in severe CAH, predominant in CAH without cirrhosis compared with those in CAH with cirrhosis. There was a tendency of inverse correlation between HBV replication activity and liver disease activity. The results above were in line with the concept that HBcAg expressed on the surface of infected hepatocytes may be relevant target for T lymphocyte cytotoxicity. The results have suggested that an immune response to HBV is present, leading to the destruction of most infected cells. 3. There was a positive correlation between HBV-DNA in serum and HBcAg in the liver (P less than 0.005), indicating that HBV-DNA in serum can represent HBV replication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591936 TI - [Study on leukemic-colony forming unit in 31 patients with acute non-lymphocytic leukemia]. AB - Thirty-one patients with acute non-lymphocytic leukemia (ANLL) were studied with Dicke's soft agar marrow culture to identify leukemic colony forming units. Eighteen of them had leukemic colony formation, in those patients, the average survival period was shorter (65d), and none of them achieved remission after chemotherapy. The remaining thirteen patients had no colony formation and had a longer survival period of 119.8 d. In the latter group four out of six who had undergone more than two courses of chemotherapy went into complete remission. Our study showed that patients who had leukemic colony formation had a worse prognosis than those who had no leukemic colony formation. PMID- 2591938 TI - [Diagnostic evaluation of coronal CT scan in skull and brain diseases]. AB - Coronal computed tomography findings in 30 cases of skull and brain diseases, including glioma 6 cases, meningioma 4 cases, acoustic neurinoma 3 cases, intraorbital tumor 3 cases, paranasal sinus tumor 3 cases, pituitary adenoma 2 cases, craniopharyngioma 2 cases, nasopharyngeal carcinoma 2 cases, empty sella 1 case, subdural hematoma 1 case, infarction 1 case, subarachnoid cyst 1 case, and metastasis 1 case are reported. The results show that as an adjunct to the axial computed tomography coronal CT scan provides valuable additional diagnostic informations. Coronal CT methods are also discussed. PMID- 2591937 TI - [Surgical treatment of primary pulmonary cryptococcal granuloma--report of 4 cases]. AB - Primary pulmonary cryptococcal granuloma is not common in Sichuan. The diagnosis of this disease is difficult to make because the patient has no characteristic symptoms and the chest X-ray findings of the mass are not easily differentiated from carcinoma of the lung. The incidence of this disease is apparently increasing. Pulmonary cryptococcosis may be disseminated hematogenously to the meninges and cryptococcal meningitis is very difficult to treat. If the pulmonary lesion is localized, the patient's general condition is good with no evidence of systemic lupus erythematosis, diabetes, leukemia or lymphoma, partial resection of the lung is indicated. But, if the patient has a history of recent cryptococcal meningitis, surgery must be deferred. Four cases of primary pulmonary cryptococcal granuloma have been treated surgically supplemented with medical therapy in the First Affiliated Hospital from 1986 to 1987. Follow-up of more than one year showed good results in each case. PMID- 2591940 TI - [Clinical evaluation of CES-D in neurosis]. AB - A survey of 141 (male 84, female 57) neurotics was carried out by using the center of epidemiological survey-depression scale, CES-D. The results showed that the depressive symptoms were very common and the prevalence of definite depressive symptoms was 85.8%. The mean of the total score based upon 20 items of CES-D was 2.7 times the mean of the total score in the Chinese normal population. The most common depressive symptoms were unhappy, low mood, sad and hollow feeling. In addition, the mean of the total score and certain individual item scores in depressive neurotics were higher than those in neurasthenia. It is suggested that CES-D may be useful to differentiate some subtypes of neurosis. PMID- 2591939 TI - [Indications of cesarean section for severe heart diseases in pregnancy--an analysis of 61 cases]. AB - Sixty-one cases of severe heart diseases were treated between Jan. 1977 and Dec. 1986, accounting for 18.37% of the heart diseases in pregnancy. Of these 61 cases, 39 (63.93%) underwent cesarean section under continuous lumbar epidural anesthesia. The systolic/diastolic blood pressure and mean arterial pressure (MAP) values decreased from the beginning of anesthesia to the end of delivery, and then the values gradually went up to the preoperative level. During the operation, no heart failure occurred. In 22 cases (36.07%), when labor began, the systolic/diastolic pressure and MAP increased and attained the peak value during parturition. After the fetus was delivered, the blood pressure decreased immediately. In 10 cases, heart failure occurred during labor. The adjusted mortality was 4.92%. Two patients died after vaginal delivery. Of these, one had heart failure during labor and underwent cesarean section, but she died after the operation. It was noted that hemodynamic change during cesarean section was smaller than that during vaginal delivery. If an appropriate time is selected for termination of pregnancy or cesarean section is only performed in the early stage of labor, heart failure and fatal outcome may be avoided. PMID- 2591941 TI - [A fast determination of serum bilirubin with the interference from hemolysis and turbidity by three wavelength spectrophotometry]. AB - In determination of bilirubin in serum by means of color reaction when hemolysis and turbidity are present, the reliability of the measurement is decreased by the interference from hemoglobin and other turbidities. Direct measurement of bilirubin in serum by three wavelength spectrophotometry at 500 nm, 450 nm and 370 nm instead of by color reaction, provides a fast, semi-micro and accurate way without the use of any reagents. Besides the rise of the baseline by blood cells and turbidities can be corrected without the consideration of hemolysis. Under the given experimental condition, the mean recovery is 96.3 +/- 2.41% (n = 6), coefficient of variation (CV) is 4.0%. PMID- 2591942 TI - Proliferative stimuli in the normal breast: estrogens or progestins? PMID- 2591943 TI - Oral contraceptive use influences resting breast proliferation. AB - The controversy that surrounds oral contraceptive use and breast cancer risk has arisen from epidemiologic studies, yet the direct effect of such use on breast tissue remains undefined. Breast epithelial proliferation was assessed by 3H thymidine labeling of normal lobular units dissected from benign biopsies of 347 females aged 14 to 48 years. Factors shown to influence this response included cycle phase, time since menarche (breast age), and parity status. Multivariate analysis allowing for these influences was used to compare activity of natural cycles and those artificially regulated by oral contraceptives (OC). The increased activity in nulliparous OC users was highly significant (P less than .005). Comparing the effect of differences in OC type, whether combined, triphasic, progestin only, or according to estrogen or progestin content, showed a heterogeneity in response that was significant (P less than .01). Examined specifically, the formulation of OC according to progestin content did not have a significant influence, although progestin-only OC was most active, while the influence of increasing estrogen content was significant (P less than .05). However, emphasis is given to acknowledging the multiple factors and interactive processes responsible for breast epithelial stimulation when considering strategies of intervention. PMID- 2591945 TI - Congestive heart failure due to coronary artery disease without myocardial infarction: clinicopathologic description of an unusual cardiomyopathy. AB - Cardiomyopathies (CMs) can be classified as idiopathic dilated, hypertrophic, restrictive/obliterative, and so-called "ischemic cardiomyopathy." We have observed a subgroup of patients with congestive heart failure, dilated hearts, and severe coronary artery disease in the absence of myocardial infarction and therefore not fulfilling the criteria for ischemic CM. To better elucidate this group, which we called "coronary" CM, 54 consecutive necropsy patients who had congestive heart failure were retrospectively studied. Nineteen patients had idiopathic dilated CM, 26 had ischemic CM, and nine had coronary CM. The mean age of the patients with coronary CM and ischemic CM was significantly greater than that of the patients with idiopathic dilated CM (62 +/- 10 and 64 +/- 10 years versus 47 +/- 19 years, respectively). The duration of congestive heart failure was longest in the coronary CM group (4.1 +/- 3.4 years); half of these patients died suddenly or from arrhythmias. Hearts from patients with coronary CM had marked biventricular dilatation and severe coronary artery disease (mean number of coronary arteries with more than 75% narrowing, 2.2). No acute or healed infarcts were grossly visible, but interstitial and focal perivascular fibrosis were present in the myocardium of all coronary CM hearts. Although coronary CM may comprise a subset of so-called "ischemic cardiomyopathy," these cases may also represent idiopathic dilated CM with coincidental coronary artery disease. PMID- 2591944 TI - Large B-cell lymphomas with a high content of reactive T cells. AB - Twenty-one cases of large, B-cell lymphoma with an unusually high content of reactive T lymphocytes are described in this report. Fifteen patients presented with lymphoma in nodal sites and six patients presented with lymphoma in extranodal sites. With two exceptions, all patients were more than 50 years of age. The male to female ratio was 1:2. Histologically, isolated to small groups of large lymphoid cells were intermingled with many small lymphocytes. The large cells were neoplastic and exhibited B-lineage markers; immunoglobulin light chain restriction could be demonstrated in two thirds of the cases. There was a rich infiltrate of immunophenotypically mature T lymphocytes that comprised more than 50% of the cellular population. The T lymphocytes ranged from small cells with dark, round nuclei to slightly larger cells with elongated, irregular nuclei. There were occasional medium-sized blastic cells. There was also a variable infiltrate of histiocytes with or without epithelioid features, eosinophils and plasma cells, and increased vascularity. The peculiar morphologic features were also reproduced in other sites in the four patients for whom additional histologic materials were available for examination. We postulate that the abundance of T cells results either from a florid host reaction or from cytokine secretion by the neoplastic B cells, attracting T cells to the vicinity. The morphologic and immunologic features mimic those of a variety of benign lymphoproliferative diseases, angioimmunoblastic lymphadenopathy and lymphomas arising in angioimmunoblastic lymphadenopathy, peripheral T-cell lymphoma, secondary B-immunoblastic lymphoma, and Hodgkin's disease. Careful morphologic evaluation and immunophenotypic studies using leukocyte antibodies reactive in paraffin-embedded sections are of great assistance in determining a diagnosis. PMID- 2591946 TI - Nodular paragranuloma can transform into high-grade malignant lymphoma of B type. AB - A follow-up study of 537 cases of Hodgkin's disease, lymphocyte predominance type, nodular--designated as nodular paragranuloma (NP)--found simultaneous presence of (n = 11) or subsequent transition into (n = 3) a large cell lymphoma (LCL) in 14 cases. Morphologically, the LCLs were classified in ten cases as centroblastic lymphoma (malignant lymphoma, diffuse, large cell, non-cleaved cell), in three cases as immunoblastic lymphoma (malignant lymphoma, large cell, immunoblastic), and in one case as large cell anaplastic lymphoma. Eleven of the 14 LCLs were studied immunohistologically. Five cases showed a monotypic immunoglobulin (Ig) pattern, seven were positive to the monoclonal B-cell marker Ki-B3, and three showed both monotypic Ig and Ki-B3 positivity. With anti-Ig and Ki-B3, nine of the 11 LCLs could be classified as B-cell non-Hodgkin's lymphoma. Only one case of LCL exhibited the typical phenotype of Hodgkin cells, ie, positivity to anti-CD15 (3C4) and anti-CD30 (Ber-H2). A retrospective follow-up study of these secondary LCLs of B type revealed a longer survival time than that of primary B-type LCLs and other secondary LCLs. These findings indicate that B type LCL is the most common outcome when NP progresses into a lesion of higher malignancy and provide further evidence of a close relationship of NP to the B cell system. They also suggest that it would be clinically relevant to distinguish between cases of B-type LCLs secondary to NP and cases of LCLs without association with NP. This implies that signs of a preexisting NP should be looked for when a B-type LCL is diagnosed. PMID- 2591947 TI - Relationship between eosinophil density and T-cell activation markers in lymph nodes of patients with Hodgkin's disease. AB - Hodgkin's disease (HD) is characterized morphologically by a variable infiltration of tissues by eosinophilic granulocytes. The lesions also contain numerous T cells, predominantly of the CD4+ immunophenotype. To investigate whether the presence or absence of tissue eosinophilia is related to the immunophenotype of the T cells, we studied 43 cases of HD (28 nodular sclerosing, ten mixed cellularity, and five unclassifiable) for the relative numbers of lymphocytes positive for CD2, CD3, CD4, CD5, CD8, CD25, CD38, T9, TQ1, HLA-DR, and beta F1, and for the number of eosinophils in tissue sections. By univariate and multivariate analysis, we determined that there was an inverse relationship between the number of eosinophils and the presence of TQ1+ (P less than .0005) and CD25+ (P less than .0005) lymphocytes. In addition, we observed that TQ1 stained the Reed-Sternberg cells in these lesions. We also determined that the T cells expressed HLA-DR more frequently in the nodular sclerosis subtype than in other subtypes of HD (P less than or equal to .0001). We therefore conclude that the degree of tissue eosinophilia in the lymph nodes of patients with HD may be explained, at least in part, by the immunophenotype of the T cells present in the affected lymph nodes. PMID- 2591948 TI - Concanavalin A binding sites in fetal, adult, transitional, and malignant rectosigmoid mucosa. AB - We studied mucin histochemistry in 25 rectosigmoid adenocarcinomas and in the transitional mucosa adjacent to these tumors using standard techniques for the detection of neutral and acid sialomucins and sulfomucins and the paradoxical concanavalin A (Con A) stain. This histochemical procedure selectively detects residues of mannose in glycoproteins exposed to brief steps of oxidation and reduction. Those techniques were also used to study histologically normal mucosa of specimens with carcinoma, normal rectosigmoid mucosa of patients without inflammatory or neoplastic bowel disease, hyperplastic rectal polyps, and rectosigmoid mucosa of human fetuses. Normal mucosa and hyperplastic polyps mainly contained sulfomucins and did not display Con A binding activity with any of the variants of the stain. In contrast, fetal, transitional, and malignant mucosa predominantly showed sialomucins and although not reactive with the standard Con A sequence, displayed binding activity for the lectin after short oxidative-reductive steps. These results provide further evidence that transitional and malignant mucosa produce markedly abnormal mucins whose histochemical patterns represent a re-emergence of the fetal type found during development. The principles of the paradoxic Con A reaction may be applied to unmask lectin binding activity in apparently unreactive sites. PMID- 2591949 TI - Sinusoidal dilatation of the liver as a paraneoplastic manifestation of renal cell carcinoma. AB - Prominent sinusoidal dilatation of the liver, spleen, and adrenals has been observed in nude mice with transplanted human renal cell carcinoma (RCC). To confirm whether this is a paraneoplastic manifestations specific for patients with RCC, 145 human autopsy specimens of RCC, transitional cell carcinoma (TCC) and cerebral hemorrhage (CH) were studied histologically. Sinusoidal dilatation of the liver was found in nine of 45 RCC cases. That incidence rate was significantly high when compared with three of 50 TCC cases (P less than .05) and with none of 50 CH cases (P less than .005) in which sinusoidal dilatation of the liver was found. There were no significant differences among the RCC, TCC, and CH groups in the incidence of sinusoidal dilatation in the spleen and adrenals. The sinusoidal dilatation of the liver associated with RCC was unique in that it occurred focally in the mid-zone of the hepatic lobules without any findings related to passive congestion of the central vein, endothelial damage, or hepatocellular necrosis. This change was not necessarily accompanied by abnormal liver function, although sinusoidal dilatation has been reported as one of the histologic manifestations of the nonmetastatic liver dysfunction syndrome of RCC known as the Stauffer syndrome. Sinusoidal dilatation is thought to be one of the tumor-specific manifestations and the influence of some tumor products is suggested, although the exact etiology remains unclear. PMID- 2591950 TI - Mixed gangliocytoma-adenoma: a distinct neuroendocrine tumor of the pituitary fossa. AB - A mixed gangliocytoma-adenoma occurring in the pituitary fossa of a patient who presented with acromegaly, galactorrhea, and headaches is described. Immunohistochemical studies demonstrated the gangliocytic portion of the tumor to be composed nearly entirely of ganglion cells enmeshed in their neuritic processes and disclosed focal presence of growth hormone and prolactin-secreting cells in the adenoma. Ultrastructurally, some of the larger ganglion cells contained (and were often filled with) zebra-like bodies, while the adenoma was shown to be sparsely granulated with numerous fibrous bodies. These findings support the term of mixed gangliocytoma-adenoma for these rare intrasellar tumors and provide additional support for their nature as independent neuroendocrine units. PMID- 2591951 TI - S-100 protein in glands within decidua and cervical glands during early pregnancy. AB - Strong immunoreactivity with polyclonal S-100 protein antisera and monoclonal S 100 alpha subunit antiserum was found in glandular cells of the decidua basalis and cervical polyps during early pregnancy. Immunoreactive S-100 protein was negative in glandular cells of the endometrium and cervix of nonpregnant women. It was also negative in endometrial hyperplasia and endometrial carcinoma. While the function of S-100 protein is not known, a relationship between humoral factors related to pregnancy and expression of S-100 protein gene is suggested by the results of this study. PMID- 2591953 TI - In situ and infiltrating lobular carcinoma of the male breast. AB - An 82-year-old man presented with a right breast mass. Histologic examination of an excisional biopsy showed lobular in situ and infiltrating carcinoma. The patient was phenotypically male and had fathered children. There was no history of predisposing factors to breast lesions, such as drug use or gynecomastia. In our review, this is the first case of lobular in situ and infiltrating carcinoma of the male breast in a phenotypic and apparently genotypic male. PMID- 2591952 TI - Cerebral glycogenosis, alpha particle type: morphologic and biochemical observations in an infant. AB - A 3-month-old infant with congenital hypotonia suffering from an unusual form of glycogenosis is reported. The most striking neuropathologic findings were vacuolation of neuropile and glycogen accumulation, especially in the cerebral cortex and cerebellar molecular layer. Ultrastructurally, glycogen accumulation was present mainly in neurites and astrocytic processes, and mostly appeared as rosettes (alpha glycogen particles). Biochemical analysis of glycogen in various regions of the central nervous system showed an increase of up to 100-fold. The cerebral cortex, deep nuclei, and cerebellar cortex had the highest glycogen elevations, while the cerebral white matter glycogen level was normal. Among other tissues, the heart showed a several-fold increase in glycogen content. Muscle, liver, and kidney glycogen levels were not elevated. Findings in this case and in three other reported patients with cerebral glycogenosis of alpha particle type are discussed. PMID- 2591954 TI - Lymphomatoid granulomatosis versus lymphoma of the brain and central nervous system in the acquired immunodeficiency syndrome. PMID- 2591955 TI - Two techniques for excision of brain and spinal canal. PMID- 2591956 TI - Marginal zone lymphocytes in the lymph node. PMID- 2591957 TI - Origin and nature of tubuloreticular structures. PMID- 2591958 TI - Assignment of the alpha B-crystallin gene to human chromosome 11. AB - Using a human alpha B-crystallin genomic probe and human-mouse somatic cell hybrids, the human alpha B-gene was assigned to chromosome 11 and further corroborated by in situ hybridization to normal metaphase chromosomes. This assignment confirmed and regionally mapped the locus to q22.3-23.1. PMID- 2591959 TI - Complementation of repair gene mutations on the hemizygous chromosome 9 in CHO: a third repair gene on human chromosome 19. AB - A human DNA repair gene, ERCC2 (Excision Repair Cross Complementing 2), was assigned to human chromosome 19 using hybrid clone panels in two different procedures. One set of cell hybrids was constructed by selecting for functional complementation of the DNA repair defect in mutant CHO UV5 after fusion with human lymphocytes. In the second analysis, DNAs from an independent hybrid panel were digested with restriction enzymes and analyzed by Southern blot hybridization using DNA probes for the three DNA repair genes that are located on human chromosome 19: ERCC1, ERCC2, and X-Ray Repair Cross Complementing 1 (XRCC1). The results from hybrids retaining different portions of this chromosome showed that ERCC2 is distal to XRCC1 and in the same region of the chromosome 19 long arm (q13.2-q13.3) as ERCC1, but on different MluI macrorestriction fragments. Similar experiments using a hybrid clone panel containing segregating Chinese hamster chromosomes revealed the hamster homologs of the three repair genes to be part of a highly conserved linkage group on Chinese hamster chromosome number 9. The known hemizygosity of hamster chromosome 9 in CHO cells can account for the high frequency at which genetically recessive mutations are recovered in these three genes in CHO cells. Thus, the conservation of linkage of the repair genes explains the seemingly disproportionate number of repair genes identified on human chromosome 19. PMID- 2591960 TI - The proximity of DNA sequences in interphase cell nuclei is correlated to genomic distance and permits ordering of cosmids spanning 250 kilobase pairs. AB - The physical distance between DNA sequences in interphase nuclei was determined using eight cosmids containing fragments of the Chinese hamster genome that span 273 kb surrounding the dihydrofolate reductase (DHFR) gene. The distance between these sequences at the molecular level has been determined previously by restriction enzyme mapping (J.E. Looney and J.L. Hamlin, 1987, Mol. Cell Biol. 7: 569-577; C. Ma et al., 1988, Mol. Cell Biol. 8: 2316-2327). Fluorescence in situ hybridization was used to localize the DNA sequences in interphase nuclei of cells bearing only one copy of this genomic region. The distance between DNA sequences in interphase nuclei was correlated to molecular distance over a range of 25 to at least 250 kb. The observed relationship was such that genomic distance could be predicted to within 40 kb from interphase distance. The correct order of seven probes was derived from interphase distances measured for 19 pair wise combinations of the probes. Measured distances between sequences approximately 200 kb apart indicate that the DNA is condensed 70- to 100-fold in hybridized nuclei relative to a linear DNA helix molecule. Cell lines with chromosome inversions were used to show that interphase distance increases with genomic distance in the 50-90 Mb range, but less steeply than in the 25-250 kb range. PMID- 2591961 TI - Twenty loci form a continuous linkage map of markers for human chromosome 2. AB - We have used a combination of 20 DNA markers and 1 protein electromorph, defining 20 loci, to construct a genetic linkage map of chromosome 2. These markers form a continuous linkage group of 306 cM in males and 529 cM in females. Female map distances varied from approximately twofold higher to equivalence from those of males across the map. Among the DNA markers are six well-distributed, highly polymorphic markers reflecting loci that contain a variable number of tandem repeats that will be highly efficient anchor points for the eventual application of this map to studies of human genetic disease. PMID- 2591962 TI - Recombination events that locate myotonic dystrophy distal to APOC2 on 19q. AB - We previously reported a recombination in an individual with myotonic dystrophy (DM) which placed the markers D19S19 and APOC2 on the same side of the DM locus. Haplotyping of this family with more recently characterized probes which are either tightly linked to DM or distal to the linkage group at q13.2 shows that the DM locus is distal to APOC2. This is confirmed by other recombinants where DM segregates with distal probes. Additional marker to marker recombinations in unaffected individuals are reported and support the order and orientation of the DM linkage group as pter-(INSR, LDLR,S9)-(S19,BCL3,APOC2)-(CKMM,DM)-(S22,+ ++PRKCG)-qter. The data presented here cannot determine whether DM is proximal or distal to CKMM. The consequences of this probe order for antenatal diagnosis and future research aiming to isolate the gene which is affected in DM are discussed. PMID- 2591963 TI - Complete human rDNA repeat units isolated in yeast artificial chromosomes. AB - Human ribosomal DNA has been inferred to be organized in tandem repeat units of 44 kb, of which only 13 kb is transcribed into preribosomal RNA. Unfortunately, it has remained difficult to examine the intact repeat structure directly, because even a single repeat unit is too large to be accommodated in conventional cloning systems. Here we report the isolation of intact repeat units using yeast artificial chromosomes as a cloning tool. With a spacer sequence specific to human ribosomal DNA used as a probe, 27 clones were identified among 17,000 YACs (about 0.7 genomic equivalent of total human DNA). Fourteen clones contained only a small portion of rDNA; the other 13 contained most or all of the rDNA repeat unit, and 8 of those were studied in further detail. They contained 1 to 1.5 repeat units of rDNA with all of the expected EcoRI and HindIII fragments. These clones provide possible starting material for the analysis of expression of a single unit of rDNA. Unexpectedly, however, only the four smaller clones (70 to 90 kb) were completely composed of standard rDNA sequences; four larger clones (up to 950 kb in length) contained additional "non-rDNA" sequences, at either one or both ends of the repeat unit. Analysis of these atypical rDNA clones suggests that their inserts either are scattered in the genome or are localized in a nucleolar organizer region that is more complex than previously recognized. PMID- 2591964 TI - Patterns of intra- and interarray sequence variation in alpha satellite from the human X chromosome: evidence for short-range homogenization of tandemly repeated DNA sequences. AB - A number of processes, such as sequence conversion, unequal crossingover, and molecular drive, have been postulated to explain the homogenization of tandemly repeated DNA families. To investigate the nature and extent of such processes in the alpha satellite family of centromeric DNA, we determined the nucleotide sequence of approximately 700 bp from each of 40 representative alpha satellite repeats from six sources of human X chromosomes, obtaining a total of approximately 28 kb of sequence data. Sequence divergence among the repeats examined was low, with an average pairwise difference of approximately 1%. Pairwise comparisons of all repeats indicate that the degree of similarity for those repeats in physical proximity (within approximately 15 kb) of each other is significantly greater than that for randomly located repeats, from either the same or different X chromosomes, suggesting that the mechanisms predicted to homogenize these arrays are effectively short-range in action. Analysis of individual patterns of sequence variation allows the assignment of haplotypes for five high-copy-number diagnostic positions and reveals distinct positions of equilibrium and disequilibrium within the repeat. These analyses address hypotheses about the origin of the observed patterns of variation throughout alpha satellite evolution. PMID- 2591965 TI - A human alphoid DNA clone from the EcoRI dimeric family: genomic and internal organization and chromosomal assignment. AB - We isolated an alpha satellite DNA clone (pC1.8), 17 kb long, which is composed exclusively of tandemly repeated 340-bp EcoRI fragments. Hybridization studies using 37 random EcoRI dimers subcloned from pC1.8 showed that they are heterogeneous. The sequence of 5 dimers, 3 of them adjacent, confirmed this observation and showed that the heterogeneity is more accentuated among the second monomers. The chromosomal assignment under high stringency conditions showed that this alphoid subset is located on chromosomes 1, 5, and 19. No conditions that eliminate the hybridization on any one of those chromosomes were found. This suggests that, in contrast to many other chromosome-specific alpha satellite subsets, the single chromosome subsets of this family are virtually indistinguishable by hybridization techniques. PMID- 2591966 TI - Characterization of a highly unstable mouse minisatellite locus: evidence for somatic mutation during early development. AB - A highly unstable mouse minisatellite locus, Ms6-hm, has been identified in mouse DNA fingerprints produced by cross-hybridization with human minisatellite probe 33.6. A 7-kb allele of Ms6-hm was cloned from a C57BL/6J mouse and collapsed to a 400-bp plasmid insert on propagation in Escherichia coli due to loss of the majority of minisatellite repeat units. Sequence analysis revealed that Ms6-hm has evolved by amplification within a member of the MT (mouse transcript) family of interspersed repetitive elements. Linkage analysis localized Ms6-hm near the brown coat color gene (b) on chromosome 4. Multiallelism and heterozygosity at this locus within inbred strains result from a high germline mutation rate to new length alleles (2.5% per gamete). Mice mosaic for cells carrying a nonparental allele in somatic tissue, and in some cases also in the germline, provide evidence for additional, somatic, mutation events at Ms6-hm. In two mosaic mice the fraction of cells containing the nonparental allele has been shown to be indistinguishable in different adult tissues. These somatic mutation events at Ms6-hm must therefore occur very early in development, preceding the allocation of somatic lineages, and the same pool of primitive ectoderm cells must contribute equally to all somatic tissues. Under low-stringency hybridization conditions the collapsed subclone of Ms6-hm cross-hybridizes to other unstable loci in the mouse genome to generate a novel and highly individual specific mouse DNA fingerprint. PMID- 2591967 TI - Genomic structure of the human cytosolic aldehyde dehydrogenase gene. AB - We have isolated and characterized several overlapping clones from two human genomic libraries constructed in cosmid and bacteriophage vectors. They span about 80 kbp and include the entire human cytosolic aldehyde dehydrogenase (ALDH1) gene. Restriction endonuclease mapping, Southern blotting with cDNA and specific oligonucleotide probes, and DNA sequencing were performed to analyze the cloned genomic DNA. The ALDH1 gene is about 53 kbp long and is divided into 13 exons which encode 501 amino acid residues. Primer extension results defined the transcription initiation site to 53 bp upstream from the A of the initiation codon ATG. The promoter region of the gene contains an ATA box and a CCAAT box, which are located 32 and 74 bp upstream, respectively, from the transcription initiation site. The possible functional domains of the protein encoded by exons are discussed. A similar intron-exon organization between the genes of cytosolic ALDH1 and its mitochondrial ALDH2 isozyme in which both enzymes are encoded by 13 exons and 9 of the 12 introns interrupt the coding sequence at homologous positions was observed. This is consistent with the model that the two isozyme genes evolved after the duplication of a common ancestor gene. PMID- 2591968 TI - Twenty-five loci form a continuous linkage map of markers for human chromosome 7. AB - We have constructed a primary genetic linkage map from DNA markers that define 25 loci on chromosome 7. The markers form a continuous linkage group of 141 cM in males and 340 cM in females; female genetic distances were on average more than twofold higher than those in males throughout the chromosome. The average heterozygosity of the loci was 45%. A subset of the markers can be used for efficient application of this map to studies of human genetic disease. PMID- 2591970 TI - The human alpha 2(XI) collagen gene (COL11A2) maps to the centromeric border of the major histocompatibility complex on chromosome 6. AB - Type XI collagen, a minor structural component of cartilage fibrils, is composed of three chains, alpha 1(XI), alpha 2(XI), and alpha 3(XI). Using a cloned fragment of the human alpha 2(XI) collagen gene (COL11A2) as a molecular probe for in situ hybridization and somatic cell hybrid mapping, we have localized the gene to the short arm of chromosome 6, region 21.3. By exploiting the rich source of probes provided by the major histocompatibility complex (MHC) genes, which also map to this chromosomal band, we have constructed macrorestriction maps of the region by pulsed-field gel electrophoresis and have localized the alpha 2(XI) collagen gene to the centromeric extreme of the MHC. Finally, we have demonstrated, by the isolation of overlapping cosmid clones, that the gene is 45 kb centromeric to the HLA-DPB2 locus and oriented with the 3' end toward the MHC. The COL11A2 locus thus demarcates the proximal boundary of the MHC. This finding may have implications for the understanding of certain MHC-linked diseases. PMID- 2591969 TI - Structure and expression of the rat class I alcohol dehydrogenase gene. AB - Clones containing the rat class I alcohol dehydrogenase (ADH) gene were isolated from a Charon 4A genomic library. The gene spans approximately 13 kb and comprises nine exons and eight introns. The upstream 436 bp contain canonical TATA and CCAAT sequences, an inverted CACCC box, a TG3 box found in mouse and human ADH promoters, and regions of homology to glucocorticoid response elements. The 5'-untranslated region of the ADH transcript has the potential to form a stable stem-loop structure. The first intron contains an unusual stretch of alternating purines and pyrimidines similar to that found in the same location in the mouse ADH gene. The amino acid insertion found in rat alcohol dehydrogenase results from a shift in the 3' splice junction of the fourth intron which adds an extra three base pairs to the fifth exon. Intron-exon boundaries are otherwise identical to those in mouse and human ADH genes. H4IIE cells stably transfected with plasmids containing the chloramphenicol acetyltransferase (CAT) gene fused behind the first 436 bp of the promoter region express CAT, but the CAT activity is not inducible by dexamethasone. The elements responsible for glucocorticoid stimulation of ADH gene transcription appear to reside outside of this region. PMID- 2591971 TI - Human laminin A chain (LAMA) gene: chromosomal mapping to locus 18p11.3. AB - Laminin, an integral component of basement membranes, consists of three subunit polypeptides, A, B1, and B2 chains. We have recently isolated cDNAs corresponding to human laminin A chain. These cDNAs were utilized for chromosomal in situ hybridizations to establish the genomic location of the laminin A chain gene. Metaphase chromosomes of PHA-stimulated human peripheral blood leukocytes were examined by in situ hybridization with 3H-labeled cDNAs, and the chromosomes were identified by R-banding (fluorochrome-photolysis-Giemsa method). The results indicated that the human laminin A chain is at locus 18p11.3. Since human laminin B1 and B2 chain genes have been previously mapped to chromosomes 7 and 1, respectively, the results indicate that genes encoding human laminin chains reside in separate chromosomes. PMID- 2591973 TI - A genetic linkage map of markers for human chromosome 20. AB - A continuous genetic linkage map with five polymorphic DNA markers, including one that defines a locus containing a variable number of tandem repeats (VNTR), has been constructed from genotypic analysis of 59 large reference families. The map spans a genetic distance of 105 cM in males and 115 cM in females and provides initial anchor points for a high-resolution map of human chromosome 20. PMID- 2591972 TI - Deletion mapping of DNA markers to a region of chromosome 5 that cosegregates with schizophrenia. AB - Two independent lines of evidence support the localization of a schizophrenia susceptibility locus to the proximal long arm of chromosome 5. A partial trisomy of chromosome 5 (5q11.2-q13.3) cosegregates with the disorder in a Canadian family of Chinese descent, and DNA markers from proximal 5q cosegregate with schizophrenia (plus related disorders) in families of British and Icelandic descent. We constructed a human:hamster hybrid cell line (HHW 1064) whose only human complement is a chromosome 5 that is missing the trisomic region associated with schizophrenia. In combination with a "matched" cell hybrid (HHW 105) containing an intact chromosome 5, we physically mapped DNA markers relative to the trisomy. "Schizophrenia-linked" DNA markers p105-153Ra (D5S39) and p105-599Ha (D5S76) map within the trisomy and proximal to the 5q11.2 breakpoint, respectively. The hybrid cell lines HHW 105 and HHW 1064 together provide a means to identify and generate syntenic DNA markers to further investigate the location of a schizophrenia locus. PMID- 2591974 TI - The Santa Cruz Workshop--May 1985. PMID- 2591975 TI - Commingling analysis of obesity in twins. AB - Evidence is presented for multiple components in the distribution of human fatness across several large twin samples, after removing age effects and allowing for residual skewness in component distributions. The upper component distributions corresponded to overweight or obesity in samples of middle-aged or older individuals. A bivariate analysis demonstrated that, while monozygotic co twins appeared to be drawn from the same component distributions (normal or overweight), the twin correlations varied across components, with the lowest correlation in the overweight group. While these analyses cannot provide a definitive test of competing genetic and environmental hypotheses, this approach is useful for generating hypotheses about the causes of obesity. When combined with other published literature, our results suggest that the genetic background largely determines the propensity to become obese. Whether a predisposed person becomes obese and the extent of obesity depend on environmental exposures that are largely independent of early family experience. Both genes and environment appear to be important in obesity, but it appears that some genotypes may be much more sensitive to the environment than are others. PMID- 2591976 TI - HLA antigens in three populations of India. AB - In blood samples from a Hindu population of Uttar Pradesh (North India) and from two Muslim groups, one from Andhra Pradesh (South India) and the other from Gujurat (West India), frequencies of 38 HLA-A, -B and -C antigens were investigated. Eight antigens - A23, A25, A29, A32, Bw45, B21, Bw22 and Bw53 - were absent in the Hindu population, four different antigens - A29, Bw52, B14 and Bw42 - were absent in Hyderabad Muslims, two antigens - A31 and Bw45 - were lacking in Surat Muslims. The three populations showed considerable genetic heterogeneity. The genetic difference between the two Muslim groups was small, but the Hindu population showed pronounced differences from each of the Muslim groups. PMID- 2591977 TI - A new glucose 6-phosphate dehydrogenase variant (G6PD Thessaloniki) in a patient with idiopathic myelofibrosis. AB - A new deficient glucose 6-phosphate dehydrogenase (G6PD) variant, G6PD Thessaloniki, which was found in the red blood cells of a 70-year-old woman who had idiopathic myelofibrosis, is described. G6PD Thessaloniki had a low Michaelis constant (Km) for G6P (20 microM), high Km for NADP (10.1 microM), normal pH optimum, reduced heat stability, decreased electrophoretic mobility (96-98% of the normal), increased 2-deoxy-G6P and decreased galactose 6-phosphate utilization. Several other enzymatic activities measured in the patient's red blood cells were normal. Studies of red blood cell survival and glucose utilization gave evidence of haemolysis caused by defective glucose utilization by the pentose phosphate pathway. The only son of the patient had normal G6PD in his red blood cells. In an attempt to investigate the origin of G6PD Thessaloniki, heat stability tests of G6PD extracted from the patient's skin have been performed. PMID- 2591978 TI - Complement C6 and C7 polymorphisms in Japanese patients with chronic glomerulonephritis. AB - C6 and C7 types were studied in 158 Japanese patients with different types of chronic glomerulonephritis: 75 patients with IgA nephropathy (IgA-N); 49 patients with idiopathic membranous nephropathy (IMN), and 34 patients with minimal-change nephrotic syndrome (MCNS). There were significant differences in the C6 and C7 allele and phenotype frequencies between the patient groups and controls. A strong association was found between IgA-N and C7 5 phenotype (p less than 0.001, RR = 12.71), and between MCNS and C7 5 phenotype (p less than 0.001, RR = 14.20). A significant association between MCNS and C6 B2 phenotype (p less than 0.05, RR = 2.42) was also found. In the IMN patient group, a significant association with C7 4 phenotype (p less than 0.05, RR = 2.42) was observed. Thus, C6 and C7 phenotypes may be causative factors in the development of chronic glomerulonephritis. PMID- 2591979 TI - HLA associations with obesity. AB - A subgroup of 351 subjects with human leukocyte antigen (HLA) typing were available from the Framingham Heart Study for analyses to identify associations with obesity. The subjects consisted of 143 males and 208 females aged 58-88 years at the 15th biennial examination in 1978. The obese classification was based on maximum body mass index (BMI) over the 16 available biennial examinations of the Framingham Heart Study. The subjects were classified as obese if they exceeded the 95th percentile of BMI for 20- to 29-year-old subjects as described in the NHANES II study; males were obese if BMI greater than 31.1 and females were obese if BMI greater than 32.3. There were 27 obese males (18.9%) and 44 obese females (21.2%) in the sample. Gene frequencies were compared between the nonobese and obese groups for the pooled sample as well as by sex. Among alleles previously shown to be related to obesity, HLA Bw35 appeared to be more frequent in obese females but these data did not confirm a difference for the B18 or Cw4 alleles. More importantly, HLA Aw30 was found to be significantly higher among the obese subjects in both males and females. Further analyses adjusting for potential confounding variables reduced the estimated relative risk for obesity for subjects with the Bw35 allele to approximately 1.30 and no longer significant for this sample size. In contrast, the relative risk for Aw30, while reduced, remained significant after adjustment for confounding variables. Based on these data, individuals with the Aw30 allele have a relative risk of 2.61 for obesity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591980 TI - Probability of paternity in paternity testing using the DNA fingerprint procedure. AB - For the purpose of applying DNA fingerprinting to paternity testing, we established a general formula to calculate the probability of paternity and evaluated the ability of DNA fingerprinting to determine paternity. PMID- 2591981 TI - Genetic studies of low-abundance human plasma proteins. XII. A new variant of corticosteroid-binding globulin detected by isoelectric focusing/immunoblotting. AB - Thin-layer polyacrylamide gel isoelectric focusing over the pH range 3.5-5 followed by immunoblotting was used to investigate the occurrence and frequency of genetic variation in corticosteroid-binding globulin (CBG). Plasma samples from US Caucasians (n = 105) and US Blacks (n = 106) from Pittsburgh, Pa., Canadian Indians from Vancouver Island (n = 91) and Nigerian Blacks (n = 116) were analyzed. A complex isoprotein pattern was observed in all individuals tested. Reduction of this pattern to a single primary band following neuraminidase treatment indicates that the observed intraindividual variation is due to variation in the number of sialic acid residues associated with CBG. The CBG variant pattern consisted of a series of isoprotein bands having the same mobility as the common pattern, and a second series of bands at a more acidic isoelectric point. This pattern is consistent with heterozygosity for a rare CBG allele. PMID- 2591982 TI - Frequency of the ESD*5 allele in a Spanish population. AB - The red blood cell esterase D (ESD) polymorphism was studied by means of IEF in a North-East Spanish population (Barcelona). Gene frequencies in 430 unrelated individuals were ESD*1: 0.888, ESD*2: 0.091 and ESD*5: 0.021. Our data confirm previous results showing that ESD*5 occurs in polymorphic frequency and has a Caucasian origin. PMID- 2591983 TI - Influence of nutritional factors on 239Np and 233Pa retention in weanling rats. AB - The estimated intestinal absorption after a single administration of 239Np nitrate to fasted weanling rats (about 2% of the oral dose) was ten times higher than that of 233Pa administered as the chloride. Rats drinking tomato juice, apple juice or tea instead of water had a similar retention to the control group. However, when a small amount of tea was administered immediately before 239Np, the absorption and retention values were six times lower. When animals received only milk or glucose, the whole body retention of 239Np and 233Pa increased about 20 and 200-300 times, respectively, due mainly to a very high retention in the large intestine. When rats were fed milk plus rat chow, the whole body and gut retention of 233Pa was only two and three times higher, respectively; in the other organs less 233Pa was found than in control animals. This indicates that the extremely high retention of radionuclides in the gut contents of young rats fed only milk is temporary and disappears when solid food is available. PMID- 2591984 TI - Oral and dermal pharmacokinetics of triclopyr in human volunteers. AB - Blood levels and urinary excretion of triclopyr, the active ingredient in Garlon herbicides, were followed in six volunteers given single oral doses of 0.1 and 0.5 mg/kg body weight. Five of these volunteers later received dermal applications of Garlon 4 herbicide formulation equivalent to 3.7 mg triclopyr/kg body weight applied to the forearm. Following oral administration blood levels peaked at 2-3 h and declined to undetectable levels within 48 h; more than 80% of the dose was found as unchanged triclopyr in the urine. A two-compartment pharmacokinetic model was used to describe the time-course of triclopyr clearance; half-lives for the rapid initial and slower terminal phases were 1.3 h and 5.1 h respectively, and were independent of dose. Due to the slow half-life for dermal absorption (t1/2 = 16.8 h) the rapid initial elimination phase was obscured and the pharmacokinetics could be simplified by a one-compartment model. An average of 1.37% of the applied dose was recovered in the urine; when corrected for recovery after oral administration this was equivalent to an absorption of 1.65%. Triclopyr is slowly absorbed through skin and is rapidly eliminated. It has very low potential to accumulate in man or to be absorbed through the skin in acutely toxic amounts. PMID- 2591985 TI - Effect of subacute oral intake of the food antioxidant butylated hydroxyanisole on clinical parameters and phase-I and -II biotransformation capacity in man. AB - A study is presented in which eight healthy male non-smoking volunteers ingested a daily amount of 0.5 mg/kg butylated hydroxyanisole (BHA) for 10 consecutive days. Blood samples were taken on days -6 and 0 before and on days 4 and 7 after the first BHA administration for the assessment of standard clinical plasma parameters (L-aspartate aminotransferase, L-alanine-aminotransferase, L-gamma glutamyltranspeptidase, creatine phosphokinase, lactate dehydrogenase, total protein, albumin, urea, creatinine, Na+, and Cl-). Antipyrine (500 mg p.o.) and paracetamol (500 mg p.o) were administered before and during BHA administration as test substances to measure phase-I and phase-II biotransformation capacity. Saliva samples and urine were subsequently collected for the assessment of kinetic parameters (e.g. saliva elimination half-life, saliva clearance, apparent volume of distribution) and urinary excretion of metabolites. Kinetic plasma parameters of BHA itself were determined in plasma samples obtained via a catheter in an arm vein after oral BHA intake on days 0 and 7. Levels of antipyrine, paracetamol, BHA and metabolites in plasma, saliva or urine were quantified by standard or newly developed reversed-phase high-performance liquid chromatography methods. Urinary excretion of Na+, K+, and Cl-, as well as osmolality of urine were measured on three days before and six days during BHA administration. Generally, no significant differences were detected in the parameters measured, indicating that oral administration of BHA to men for 10 days remains without effects on clinical biochemical parameters and phase-I and phase-II biotransformation capacity. In contrast, urinary excretion of metabolites of BHA was significantly increased on days 3 and 7 vs. the first day of BHA administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591986 TI - Effect of nicotine and cotinine on the production of oxygen free radicals by neutrophils in smokers and non-smokers. AB - 1. Neutrophils play a role in the pathogenesis of ulcerative colitis. Most of the patients with ulcerative colitis are non-smokers. 2. Neutrophil function was examined in healthy males, five smokers and five non-smokers, measuring production of oxygen free radicals by chemiluminescence. 3. The chemiluminescence was examined in the presence of nicotine and its main metabolite cotinine in various concentrations. 4. 10 mM nicotine inhibited production of oxygen free radicals (90.2% +/- 11.6) compared with controls (P less than 0.001), as did the same concentration of cotinine (58.9% +/- 34.2), (P less than 0.05). 5. 1 mM solutions had no effect and 3 mM nicotine was required to achieve 50% inhibition. 6. Smokers and non-smokers did not differ. 7. Since plasma concentrations of nicotine after a cigarette are only between 5 and 15 mM, the observed effects of nicotine and cotinine in much higher pharmacological concentrations in this system are unlikely to be of clinical relevance in ulcerative colitis. PMID- 2591987 TI - Total exclusion from external respiration protects lungs from development of fibrosis after paraquat intoxication. AB - Most survivors of paraquat intoxication go on to develop fibrosis of the lung leading to death within a few weeks. The pathogenic effects of paraquat are based on the formation of oxygen free radicals. A cascade reaction occurs at the cell membrane which is damaged and cell integrity is destroyed. Fibroblasts migrate into the damaged region leading to the laying down of collagen and subsequent fibrosis. Currently paraquat intoxication is treated with gastrointestinal lavage, haemoperfusion and haemodialysis with mixed results. Artificial respiration with low percentage of inspired oxygen is instituted in order to decrease the possible release of oxygen radicals. However, in most cases, developing fibrosis prevents this treatment continuing and requires increased concentrations of inspired O2 and increased ventilation pressure. The combination of increased FiO2 and barotrauma leads to a vicious circle of parenchymal lung damage. In this study we present a treatment designed to avoid the development of lung fibrosis using total exclusion of segments of the lung from external ventilation. Exclusion from external ventilation was performed in animal experiments by instillation of Ethibloc, an amino acid glue, in one main bronchus to create an atelectasis. In different experimental groups this procedure was performed before and after intraperitoneal intoxication with paraquat. Four to twelve days later the experimental animals were sacrified and the ventilated lungs and the atelectatic lungs were compared. The ventilated lungs showed dose dependent damage to the alveolar epithelium and gross interstitial oedema. In some cases fibrosis was seen. The atelectatic parts of the lung were not different from the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2591988 TI - A comparative prospective study of self-poisoned patients in Trondheim, Norway between 1978 and 1987: epidemiology and clinical data. AB - 1. In a prospective study of patients hospitalized for deliberate self-poisoning between 1978 and 1987 the number of admissions increased from 303 to 425. The annual incidence increased significantly for both women (P less than 0.05) and men (P less than 0.01). The mean age decreased significantly in the male group (P less than 0.05), but increased in the female group (P less than 0.05). 2. The median latency time for patients presenting at the hospital was short; 3.7 h in 1978 and 2.9 h in 1987. 3. There was a significant reduction in the percentage using barbiturates (9% in 1978 and 1% in 1987; P less than 0.001) and the use of benzodiazepines increased (18% in 1978 and 32% in 1987; P less than 0.05). The percentage of unconscious patients did not change significantly. 4. In 1987 N acetyl-cysteine was the most frequently used antidote. Physostigmine has almost been abandoned since 1978. 5. Significantly more patients were hypotensive in 1978: 24% vs 11% in 1987; (P less than 0.001) and significantly less patients needed treatment in the central intensive care unit (2% in 1987 and 5% in 1978; P less than 0.05). Complications were few (8-10%) and the mortality low (approximately 1%) in both years studied. 6. The mean duration of hospitalization in 1978 was 65 h vs 30 h in 1987, (P less than 0.001). PMID- 2591989 TI - Exposure to paraquat through skin absorption: clinical and laboratory observations of accidental splashing on healthy skin of agricultural workers. AB - Data concerning 15 consecutive cases of single exposures of the skin or eyes during work to paraquat solutions are presented. Urine and serum were analysed for paraquat in all these cases at the laboratory of the Israel Poison Information Center. From these data it is apparent that a single exposure of healthy skin to paraquat solutions caused only local lesions. No systemic effect was detected in these patients. PMID- 2591991 TI - Acute renal failure following accidental cutaneous absorption of phenol: application of NMR urinalysis to monitor the disease process. AB - An unusual case of acute renal failure is reported following accidental cutaneous absorption of phenol and exposure to dichloromethane. Renal function during the onset of the nephrotoxic episode and the subsequent recovery period was monitored using a combination of standard clinical biochemical techniques and high resolution 1H-NMR urinalysis. The initial urine biochemical patterns (up to 2 weeks following exposure) showed amino aciduria, glycosuria and lactic aciduria consistent with renal cortical necrosis. There followed a period of polyuria revealing a biochemical pattern (succinic aciduria, dimethylaminuria and N,N dimethylglycinuria) consistent with renal papillary damage. Haemodialysis was required for a period of 3 weeks and the patient was discharged 42 days after admission to hospital when renal function was normal by standard clinical chemistry criteria (urea, potassium, sodium, creatinine, calcium, phosphate, urine glucose and protein). 1H-NMR spectroscopic urinalysis revealed residual renal biochemical abnormalities consistent with renal papillary damage that were not detected by conventional analytical techniques. One year after the incident the patient is still polyuric, passing up to 3 l of urine a day. PMID- 2591990 TI - Toxicological data after heroin overdose. AB - Capillary gas chromatography with selective nitrogen detection was employed to quantify morphine and 6-monoacetylmorphine in biological fluids and tissues in five deaths attributed to heroin injection overdose. The minimum lethal concentration found was 0.021 micrograms morphine per ml of blood. In all cases, 6-monoacetylmorphine was identified in urine, confirming heroin abuse. PMID- 2591992 TI - Pharmacokinetics and toxic effects of diltiazem in massive overdose. AB - A 50-year-old man with ischaemic heart disease took 98 tablets of diltiazem 60 mg with alcohol. He developed a junctional bradycardia, hypotension and reduced cardiac function refractory to intravenous calcium gluconate. He survived with temporary cardiac pacing and infusion of dopamine. As much as half the dose was vomited back, but nonetheless the plasma diltiazem concentration reached 6090 micrograms/l before falling mono-exponentially with a half-life of 8.6 h. Sinus rhythm returned when the plasma concentration of diltiazem was around 750 micrograms/l. Standard resuscitative procedures sufficed to treat massive diltiazem overdosage. PMID- 2591993 TI - The rarity of liver toxicity in patients treated with coumarin (1,2-benzopyrone). AB - 1. Two thousand, one hundred and seventy-three patients with cancer or chronic infections were treated with coumarin in a clinical trial. 2. 0.37% of these patients developed elevated liver enzyme levels during therapy with coumarin. 3. This hepatitis was probably a form of idiosyncratic hepatotoxicity and may have been immune in origin. PMID- 2591994 TI - Self-poisoning in Sri Lanka: factors determining the choice of the poisoning agents. AB - Sri Lanka is a developing agricultural country with a high fatality rate due to self-poisoning with very toxic agrochemicals as the main poisoning agents. A prospective study of 97 consecutive admissions following self-poisoning reveals that easy availability of the agrochemicals together with the lack of knowledge regarding their lethality were the main causative factors determining the choice of poisoning agents. Developing community awareness of the lethality of these substances, educating the farmers with regards to proper storage and disposal of agrochemicals together with stricter legislation regarding their sale and distribution may reduce the incidence of self-poisoning due to these agents with a consequent reduction in mortality due to self-poisoning. PMID- 2591995 TI - Intracellular localization of cerium. A microanalytical study using an electron microprobe and ionic microanalysis. AB - Radioactive cerium is a nuclear toxicant. Metallic cerium is used in industry. Aspects of the intracellular metabolism of this element were studied following intraperitoneal injection and aerosol exposure in rat. Two microanalytic methods, an electron microprobe and ionic microanalysis, enabled the sites of incorporation and the process of intracellular concentration of cerium to be determined in the liver, lung, kidney, bone marrow and bone tissue. The very high sensitivity of ionic analysis enabled very low concentrations of cerium to be detected with a spatial resolution of 0.5 microns. Microanalysis by electron microprobe permitted: (i) the lysosomal localization of cerium to be determined; and (ii) the lysosomal coprecipitation of cerium with phosphorus to be demonstrated. Results are discussed in relation to aspects of radiological protection. PMID- 2591996 TI - Seven warning signals of cancer (SWSC) and screening for cancer. AB - SWSC was used as a tool to detect cancer in persons who attended the Cancer Detection Camps. Seven Cancer Detection Camps were conducted in rural and urban areas of Andhra Pradesh, India. Out of 1,079 persons screened, 517 complained of one of the SWSC. Fifty five malignant and eight premalignant lesions were detected. SWSC as a tool for detection of Cancer in a camp setting appears effective. PMID- 2591997 TI - Clear cell sarcoma of kidney (CCSK)--a clinicopathological study of 4 cases. AB - The clinical and histopathological features of four cases of clear cell sarcoma of kidney (CCSK) or Bone metastasising renal tumour of childhood (BMRTC) are presented. These cases were identified among 107 primary renal tumours in childhood over a period of 15 years (1973-1987) in the Trivandrum Medical College. Of the 107 cases 96 (89.7 percent) were nephroblastomas and 7 (6.6 percent) were Mesoblastic Nephromas. The incidence of Clear cell sarcoma was 3.7 percent. Abdominal mass and haematuria were the most common clinical features. All the four cases occurred in male children with no predilection for the right or the left kidney. At the time of presentation bone metastasis was not present in any of the four cases. Metastasis to scapula and skull was detected ten months after nephrectomy in one case. Of the four patients three were in stage I disease at the time of diagnosis. All the four cases showed the typical gross morphology and the classic microscopic pattern of Clear Cell sarcoma kidney. The treatment was similar in all the four cases with Surgery followed by radiotherapy and chemotherapy (Vincristine, Adriamycin Actinomycin D and cyclophosphamide). Only one of the four patients is alive and well 12 months after surgery. The literature is reviewed along with a discussion of the gross pathology, histology and histogenesis of clear cell sarcoma of kidney. PMID- 2591998 TI - Tuberculosis in patients with malignant disease. AB - Of 2,143 biopsy proven cancer patients seen at our hospital over a six year period, 4 (0.19%) patients developed active tuberculosis (TB) during anticancer therapy or shortly after its completion. The cancer diagnoses of those patients were non-Hodgkin's lymphoma, breast cancer, chronic myelogenous leukemia, and astrocytoma. Institution of antituberculous therapy was successful in three patients, however, the TB course was rapidly fatal in the fourth patient with non Hodgkin's lymphoma despite therapy. The association between TB and neoplasia is emphasized. TB complicating malignant disorders represents complex problem regarding its early recognition and its managements. PMID- 2591999 TI - Hodgkin's disease with bone marrow involvement. AB - Bone marrow involvement was seen in 11 percent of patients with Hodgkin's Disease which was determined from pre-treatment biopsy specimens using established histopathologic criteria. Analysis of 32 evaluable patients with marrow involvement showed male preponderance with a peak in fourth decade of life. Twenty four cases (75%) had B-symptoms and 15 (46%) presented within six months of onset of symptoms. On categorizing for clinical staging, 21 (65%) belonged to stage III and IV. Hepatomegaly (greater than or equal to 2 cms) was present in seven cases (21%) and splenomegaly in 13 cases (40%). Mixed cellularity and lymphocytic depletion histopathologic subtypes showed the highest frequency of involvement (21 cases; 65%). Out of 28 cases ESR was raised in 27 cases (96%). Eighteen cases (56%) showed elevated serum alkaline phosphatase levels. Serum copper levels were determined in 14 cases, out of which 12 (85%) showed elevated levels. These parameters along with anemia (hemoglobin of 12 g/dl or less) in 26 cases (81%), correlated well with the disease activity. Only four cases had leukopenia at presentation pointing to no hindrance for aggressive chemotherapy. All cases received minimum of six courses of standard combination chemotherapy with or without local radiotherapy. Sixteen cases (50%) relapsed subsequently and were managed accordingly. A five year follow-up revealed a minimal 31 percent overall survival, and 18 percent of patients were disease free and well since the time of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592000 TI - Chromosome analysis in effusions as a diagnostic adjunct to cytology. AB - Cytogenetic analysis using G-banding techniques for the diagnosis of malignancy in pleural and peritoneal effusions is compared with the results of traditional cytomorphology. The studies indicate that the yield of mitotic cells in malignant effusions is quite high when compared to fluids with no cytological evidence for malignancy. Chromosome criteria for malignancy are of special value in the differential diagnosis of reactive cells versus malignant cells, which pose problems when cytological evaluation alone is considered. Cytogenetic analysis can be performed rapidly and used side by side with conventional cytological procedures to obtain higher sensitivity for cancer diagnosis. PMID- 2592002 TI - Effect of tea on 12-O tetradecanoyl-phorbol-13 acetate (TPA) induced promotion of transformation in JB6 mouse epidermal cells. AB - The extract of black and green tea (Camellia sp.) which are widely consumed as commonest beverage, decreased the 12-O-Tetradecanoylphorbol-13 acetate (TPA) induced promotion of transformation in dose dependent manner in JB6 mouse epidermal cell system. The probable mechanisms have been discussed. PMID- 2592001 TI - Cisplatin-based chemotherapy in advanced ovarian cancer: initial experience in an Indian set-up. AB - Forty patients of advanced ovarian carcinoma were treated with monthly cycles of cyclophosphamide, adriamycin and cisplatin. Debulking surgery was done in 29 cases. Clinical complete response was seen in 70 percent and an overall response in 85 percent of cases. The median follow-up was 30 months. The actuarial overall survival was 45 percent and the disease free survival was 35 percent at 3 years. The present protocol appears to have an important influence on initial control of disease but relapses continue to occur following the treatment. Cytoreductive surgery before or after three cycles of chemotherapy has a favourable influence on disease free survival (DFS). Prolonged follow up will be necessary to determine the overall influence on long term survival. PMID- 2592003 TI - Control of persistent vesical bleeding due to radiation cystitis by intravesical application of 15 (S) 15-methyl prostaglandin F2-alpha. AB - A 45 year old female who received radiotherapy for stage II-B uterine cervical cancer four and half years ago, presented with persistent hematuria due to radiation cystitis. 15 (S)-15-methyl prostaglandin F2-alpha (1 mg in 100 ml of normal saline) was instilled into the bladder daily for two days. The severity of bleeding decreased considerably. However, significant hematuria recurred 19 days later which continued despite bladder irrigation with normal saline. 1 mg of 15 (S) 15-Me PGF2 alpha mixed with hydroxyethyl cellulose gel to a volume of 10 ml was then instilled into the urinary bladder daily for three days and macroscopic hematuria ceased. Urinary frequency and urgency were the side effects which lasted for ten days. There has been no recurrence of macroscopic hematuria during the five months follow-up. In conclusion, 15 (S) 15-Me PGF2-alpha may be administered intravesically to control moderate hematuria due to radiation cystitis. PMID- 2592004 TI - Ontogeny of secretory component in rat liver. AB - The ontogeny of the expression of secretory component (SC), the receptor for transepithelial transport of polymeric immunoglobulins, in the rat liver was assessed by measuring the SC concentration in liver homogenates of rats killed from birth to 60 days of age, and by quantifying the daily SC secretion of in vitro cultured hepatocytes isolated from rats similarly killed from 2 days before birth to 60 days of age. With both methodologies, only very small amounts of SC were produced by the rat liver up to 20 days of age, whereafter expression of SC markedly increased. The development of SC production in the rat liver was co ordinate with that previously reported in the rat small intestine, preceding the appearance of large numbers of intestinal IgA plasmacytes. These data further emphasize the importance of the liver contribution, via the bile, to the intestinal secretory IgA system of the rat. PMID- 2592005 TI - Role for T cells, IL-2 and IL-6 in the IL-4-dependent in vitro human IgE synthesis. AB - The role of T cells and monocytes, as well as that of cytokines, such as IL-1, IL 2 and IL-6, on the IL-4-dependent in vitro human IgE synthesis was investigated. Recombinant IL-4, IL-4-containing T-cell clone supernatants and different combinations of recombinant cytokines failed to induce highly purified B cells to synthesize IgE. IL-4-dependent IgE synthesis was restored by addition to purified B cells of either untreated or mitomycin C-treated autologous T lymphocytes. Addition to purified B cells of autologous monocytes did not restore the IgE response, but usually it exerted a potentiating effect on the synthesis of IgE induced by IL-4 in the presence of suboptimal concentrations of T cells. The activity of T cells apparently preceded that of IL-4 and required a physical contact with B cells. The presence in culture of IL-2 also appeared to be necessary for the T-cell and IL-4-dependent IgE synthesis. Even though not essential, IL-6 was able to potentiate IgE synthesis in most experiments, whereas IL-1 did not display any modulatory effect. PMID- 2592006 TI - The effect of the castor bean toxin, ricin, on rat IgE and IgG responses. AB - IgE responses are closely regulated in non-atopic humans and low IgE responder animals. After an initial period of IgE production following antigen exposure, IgE synthesis appears to be actively suppressed. Inhalation of the dust of castor beans induces persistent IgE responses in atopic and non-atopic humans alike. This phenomenon was investigated in animals. Hooded Lister rats were immunized intraperitoneally with different preparations of castor bean. These had been heated for different lengths of time, 60 and 15 mins, to inactivate the toxin ricin. Immunization with as much as 100 micrograms of the extract heated for 60 min failed to produce an IgE response, while injection of 100 micrograms of the extract heated for 15 min produced a marked IgE response to castor bean proteins. Thus the component of castor bean extract which induces the IgE response appears to be heat labile. The IgE potentiating component in castor bean was found to enhance IgE responses to other antigens such as ovalbumin and when 0.8 microgram of an unheated castor bean extract was administered together with an optimal dose of ovalbumin, there was a substantial increase in ovalbumin-specific IgE but not IgG in all animals. In addition, total serum IgE but not IgG increased up to 20 fold. The effect of castor bean was more sustainable than that of an established IgE-specific adjuvant, Bordetella pertussis, and was able to boost an IgE response that had diminished and maintain an ongoing IgE response when re administered at weekly intervals. In addition, it was possible to reproduce the IgE potentiating effects with purified castor bean ricin at 25 ng/rat. The way that it produces this effect is not known but it is possible that ricin blocks the normal IgE suppressive mechanisms that regulate IgE responses. PMID- 2592007 TI - Antibody-forming cell induction during an early phase of germinal centre development and its delay with ageing. AB - The present study was initiated to determine if an early phase of germinal centre (GC) development is associated with the generation of antibody-forming cells (AFC). Germinal centres in draining lymph nodes from immune mice were examined histochemically after secondary immunization for the presence of AFC at both the light and electron microscopic levels. Additionally, peanut agglutinin (PNA) high (Hi) GC B cells were isolated, placed in cell culture and specific antibody production was monitored at successive intervals. Electron microscopy showed that plasma cells in all stages of differentiation were present within GC at 3-5 days and to a lesser extent at 7 days following antigenic challenge. Furthermore, PNAHi GC B cells obtained between Days 3 and 5 spontaneously produced specific IgG when placed in culture. Germinal centre B cells isolated either before or after this period did not produce antibody without the addition of T-cell cytokines. Induction of AFC in GC occurred at the time when GC B cells acquire follicular dendritic cell (FDC)-derived, immune complex-coated bodies (iccosomes) and process and present this antigen to helper T cells. This suggested a causal relationship between iccosome release and AFC induction. Support for this was obtained by examination of AFC induction in aged mice where iccosome release has not been observed. Peanut agglutinin-positive GC B cells isolated from aged mice on Days 3-5 after antigen challenge failed to spontaneously produce specific antibody. Collectively, these data show that GC development 3-5 days after booster immunization results in AFC generation and suggests a role for FDC iccosomes in their induction. PMID- 2592008 TI - Cholera toxin-induced fluid secretion in rat gut ligated loops: influence of bile from normal or cholera toxin-immunized rats. AB - Fresh normal rat bile premixed with cholera toxin (CT) did not significantly affect the CT-induced fluid accumulation in rat jejunal ligated loops. Bile from rats intrajejunally (i.j.) immunized three times with CT definitely inhibited CT induced fluid secretion. Bile duct ligature (BDL) for 1-4 days in unimmunized rats, in contrast with mice, did not significantly affect subsequent CT-elicited fluid secretion in their ligated loops. BDL for 4 days in rats i.j. immunized with CT, only slightly decreased the CT-neutralizing ability of their gut loops. Passive transfer during 24 hr of bile from i.j.-immunized rats, but not from normal rats, into gut of normal recipient rats with BDL, significantly protected loops made in such recipients. The affinity-purified antibodies of immune bile, mixed with CT, neutralized its effect. Our data show that, unlike mice, rat bile acids are not required for expression of the CT effect in gut loops. In addition, bile from i.j.-immunized rats contains enough anti-CT antibodies to be protective on its own, but is not necessary for substantial gut protection against CT in i.j.-immunized BDL rats. Our results confirm a major and complementary role of both biliary and intestinal secretory IgA antibodies in protection of the rat gut mucosa against CT-induced fluid secretion. PMID- 2592009 TI - Generation and characterization of monoclonal antibodies against Giardia muris trophozoites. AB - Mouse monoclonal antibodies (mAb) were produced against Giardia muris trophozoite surface antigens. To generate B-cell hybridomas, P3/NS1/1-Ag4-1 myeloma cells were fused with splenic lymphocytes from BALB/c mice that had been immunized parenterally with G. muris trophozoites. Hybridoma culture supernatants were screened for mAb by flow cytometry of G. muris trophozoites incubated with culture supernatant followed by fluorescein-conjugated anti-mouse IgG and IgM. Flow cytometry showed three types of trophozoite staining by mAb: (i) bright staining of greater than 90% of trophozoites, with aggregation of the organisms; (ii) bright staining of approximately 90% of trophozoites, with little or no aggregation; (iii) dull staining of approximately 20% of trophozoites, without aggregation. Western blotting of mAb on G. muris trophozoite antigens separated by polyacrylamide gel electrophoresis showed that a mAb exhibiting the third of these flow cytometry staining patterns recognized trophozoite antigens of MW approximately 31,000 and 35,000. Immunoprecipitation studies indicated that the same mAb specifically precipitated two 125I-labelled trophozoite surface antigens of MW approximately 30,000. Monoclonal antibodies generated in this study may facilitate the purification and biochemical characterization of trophozoite antigens that are targets for protective intestinal antibody in G. muris-infected mice. PMID- 2592010 TI - Suppress of the increase in free cytosolic calcium during the inhibition of T cell activation by an autoantibody present in the serum of leprosy patients. AB - A serum factor, believed to be an IgG autoantibody, in certain patients with lepromatous leprosy inhibits the proliferation of mitogen-stimulated lymphocytes. To investigate which stage of the cell cycle was inhibited, we examined the effect of these sera on the kinetics of lymphocyte activation induced by several mitogenic agents: phytohaemagglutinin (PHA), the calcium ionophore A23187, the phorbol ester phorbol myristate acetate (PMA) and purified protein derivative of BCG (PPD). Seven out of 54 sera tested were found to inhibit PHA-stimulated proliferation. Inhibitory sera and to a lesser extent serum IgG from leprosy patients were capable of suppressing the increase in free cytosolic calcium normally observed immediately after PHA stimulation. Subsequent stages of the cell cycle, increase in cell size, the expression of the IL-2 receptor and increase in DNA were also suppressed. The inhibitory sera was not toxic and, if addition of the sera was delayed, would not inhibit lymphocytes that had already entered the cell cycle. Using mitogenic agents which act intracellularly, the normal early increase in cell size with A23187- and PMA-stimulated lymphocytes was not affected by inhibitory leprosy sera or serum IgG, but all subsequent steps in the cell cycle were suppressed; although the inhibition of proliferation in PMA-stimulated cultures was incomplete. The mechanism of action of the inhibitory sera and derived IgG, although acting through a cell surface antigen, appears to interfere with a fundamental process in activation since the effect was seen with all of the diverse stimuli examined in this study. PMID- 2592011 TI - Surface expression of differentiation antigens on lymphocytes in the ileal and jejunal Peyer's patches of lambs. AB - The surface phenotype of lymphocytes in the ileal (IPP) and jejunal (JPP) Peyer's patches (PP) of lambs was compared using flow cytometry and immunohistology with a panel of monoclonal antibodies (mAb). The B-cell markers p220, BAS9A and surface Ig molecules were detected on 70-95% of cells from the IPP. T-cell markers were detected on less than 1% of IPP lymphocytes, confirming that the IPP in lambs contains virtually only B lymphocytes. The JPP contained a lower proportion of B cells and 16% T cells, nearly all of which expressed the CD4 molecule. Interestingly, the reactivity of a fourth B-cell markers, BAQ44a, differed from this pattern; only 12% of IPP lymphocytes were positive whereas 70% of JPP lymphocytes expressed this marker. A majority of both IPP and JPP lymphocytes (80-95%) expressed the cell adhesion molecules CD11a (LFA-1) and LFA 3. Other adhesion molecules, such as CD2 and CD44, were expressed by fewer cells from the IPP than from the JPP. MHC class I antigens were detected on more than 95% of lymphocytes from both the IPP and JPP. In the case of MHC class II antigens, more positive cells occurred in the IPP (greater than 95%) than in the JPP (80%). The in situ localization of cell-surface antigens was assessed by immunohistology. CD4+ T cells occurred in the interfollicular T-cell regions and in JPP follicles, whereas CD8+ T cells localized only in the interfollicular regions and were absent from follicles. The pattern of expression of B-cell markers, adhesion molecules and MHC antigens indicated that a gradient of increasing maturity of B cells existed within follicles from the base towards the dome region. The data presented here lend support to the notion that the IPP in lambs represents a novel B-cell lymphoid tissue with a function different from that of the conventional Peyer's patches found in the jejunum. PMID- 2592012 TI - Identification of subpopulations of mouse thymic epithelial cells in culture. AB - Mouse thymic stromal cells growing in vitro have been stained with fluorescent antibodies to identify the cells found in these cultures. By means of anti cytokeratin antibody 35 beta H11, it could be shown that nearly all the cells in the cultures were epithelial. Three other antibodies which bind to specific regions of the thymus were used to detect subpopulations of the epithelial cells. Cells growing as confluent carpets stained with antibody ER-TR5, which is specific for medullary epithelium. Antigens for two other antibodies, MD2 (known to label cells at the medullary side of the cortical-medullary junction) and CDR1 (which reacts with cortical epithelium) were expressed on the cultured cells only after the addition of exogenous signals. MD2 antigen was expressed on a very small percentage of the cells incorporated into networks as well as a few dispersed cells, and seemed related to the activity of fibroblasts. CDR1 antigen appeared on the majority of the cells organized into networks and those dispersed in the cultures. Gamma-interferon (IFN-gamma) and IL-2, lymphokines usually associated with T-cell reactivity, were found to be involved in its expression. It was possible to isolate the CDR1 subpopulation from the cultures by means of the antigen present on the surface of these cells. PMID- 2592013 TI - The null T cell in pig blood is not an NK cell. AB - Up to 50% of the blood lymphocytes in young pigs are thymus-derived, lack all subset-specific markers and appear immunologically unresponsive, with no known functional role. In an examination of their possible role in natural killing, NK activity was found in unpurified mononuclear cells and in preparations of unselected and nylon non-adherent lymphocytes (T cells and Null cells). However, NK activity was abolished by removing the E rosette forming T cells using a rat IgM anti-pig CD2 monoclonal antibody and rabbit complement, but not by control treatments with a non-binding rat IgM monoclonal reagent and complement or with any other reagent alone. Thus the resting Null T cell appears not to play a significant role in natural killing. PMID- 2592014 TI - Natural killer cell function is not diminished in the healthy aged and is proportional to the number of NK cells in the peripheral blood. AB - We studied natural killer (NK) cell subsets and NK function in young (25-35 years) and aged (75-84 years) persons by means of the single-cell assay. The subjects admitted to the study all fulfilled the SENIEUR health criteria in order to avoid confounding factors such as underlying disease or the influence of medication. We found no significant difference in the NK function between healthy young and aged persons on a per cell basis. A new application of the two wavelength immunofluorescence technique during the single cell assay made it possible to define the phenotypes of the conjugate-forming cells responsible for the natural killer function. Most of the conjugate-forming cells were CD 16 positive, and half of these were also positive for Leu 7. The CD 16 antigen disappeared from the cell surface during the effector:target interaction. T-cell markers were found on some of the conjugate-forming cells but not on the strongly bound effector cells. The NK cell function was directly proportional to the number of NK (CD 16) cells in the peripheral blood. PMID- 2592015 TI - Diverse responses of human fibroblasts to a highly purified fibroblast-activating factor from the U937 line of human monocytes. AB - The responses of human dermal fibroblasts to highly purified fibroblast activating factor (FAF), derived from supernatants of U937 human monocytes stimulated with phorbol myristate acetate (PMA), were investigated with several in vitro assays of specific synthetic functions. The highly purified peptide was detected as a single 16,000-18,000 MW protein, by both silver staining and Western blot analysis, with an antiserum generated against a synthetic peptide representing the amino-terminal sequence of 17 amino acids. At concentrations that induced similar levels of fibroblast proliferation, transforming growth factor-beta (TGF-beta), interleukin-1 (IL-1), acidic fibroblast growth factor (aFGF) and FAF also stimulated fibroblasts to generate and release prostaglandin E2 (PGE2) and proteoglycans. TGF-beta had the least effect on proteoglycan production. In contrast, the production and secretion of collagen evoked by FAF was only minimal when compared to that observed with IL-1 and aFGF. FAF and aFGF promoted fibroblast-induced collagen gel contraction with similar potency. Thus, the profile of fibroblast effects is a specific property of each cytokine. PMID- 2592016 TI - Antibodies to a short synthetic peptide related to the hinge segment of human IgG3 recognizes thermally or fixative induced conformational changes in the human IgG3 molecule. AB - A synthetic decapeptide (SP) was used to produce a murine monoclonal antibody specific for the human IgG3 molecule. Recognition of the IgG3 determinant is heat and fixation-sensitive in ELISA and immunoenzyme cytology, respectively. The antibody specifically recognizes a sequence from the hinge region of IgG3, but only when subtle alterations in the conformation are induced by mild heating (greater than 40 degrees) and subsequent stabilization by means of electrostatic interactions in solid-phase assays or by fixation with formalin acetic acid mercury chloride. The structure of the human IgG3 molecule is especially sensitive to microenvironmental influences, as can be concluded from its behaviour under various physicochemical conditions. To this, we add that the immunogenic determinants in the structure of relatively flexible parts of this protein can be severely altered by the routine application of fixation methods. It is shown that these changes can also be of importance in the recognition of antigen by monoclonal antibodies. PMID- 2592017 TI - Blocking of cytotoxic T-cell function of MOLF/Ei mice by anti-Ly 35.1 monoclonal antibody. AB - Ly 35.1 antigen is an alloantigen expressed only on T cells of Mus musculus molossinus-derived inbred strains. Previous findings indicated that the genetic locus coding for Ly 35 antigen was closely linked to Ly 2/3 on chromosome 6 and that epitopes detected by Ly 2.1 and Ly 35.1 monoclonal antibodies (mAb) were closely associated, as shown by binding inhibition assay. In this study, we examined the blocking effects of anti-Ly 2.1 and anti-Ly 35.1 mAb on cytotoxic T cell function of MOLF/Ei mice generated against BALB/c. MOLF/Ei cytotoxicity was blocked by Ly 35.1 mAb, but not by anti-Ly 2.1 mAb. Additional tests showed that cytotoxicity was blocked by Ly 3.1 mAb, but not Ly 3.2 or Ly 2.2 mAb. These results suggested that MOLF/Ei mice express Ly 3.1, but not Ly 2.1 antigen at a functional level, and that Ly 35.1 may be a functional epitope of Ly 2 antigen in the MOLF/Ei strain. PMID- 2592018 TI - HLA-C "blank" alleles express class I gene products. Biochemical analysis of four different HLA-C "blank" polypeptides. AB - Monoclonal antibodies (mAbs) W6/32, HC10, and 4E were used to precipitate class I antigens from 21 selected individuals with at least one HLA-C "blank" allele. In 19 of these individuals, characteristic HLA-C banding patterns which could be precipitated by all three HLA class I mAbs were observed on one-dimensional isoelectric focusing gels--obviously the gene products of HLA-C "blank". At least four allelic HLA-C "blank" gene products with different isoelectric points could be discerned. All of them segregated with HLA-C "blank" haplotypes in informative families; two of them were associated with HLA-B51, one with HLA-B38, and one with HLA-B18. Reactivity of the HLA-C "blank" heavy chains with mAb W6/32 indicates that they are able to associate with beta-2 microglobulin, and hence are most probably expressed at the cell surface. PMID- 2592019 TI - Two distinct subtypes of the HLA-DRw12 haplotypes in the Japanese population detected by nucleotide sequence analysis and oligonucleotide genotyping. AB - We determined the DNA sequence of the enzymatically amplified second exon of the DRB1 gene of the Drw12 haplotypes derived from three Japanese donors and found two distinct subtypes of the DRw12 haplotype. The two subtypes, designated DRw12a and DRw12b, had single-base substitutions that predicted one amino acid change at residue number 67. The sequence of the DRw12a and DRw12b subtypes differed from those of the other DR haplotypes, but in the first hypervariable region of the DRB1 gene the sequences were identical to those of the DRw8(Dw8.1) and DRw8(Dw8.3) haplotypes. The DRw12a and DRw12b subtypes were detected in a wide range of Japanese donors by genotyping with sequence-specific oligonucleotide probes synthesized according to the DNA sequences of the two subtypes. Results of this study demonstrated that the DRw12 haplotypes in the Japanese population are genetically diverse, as many other DR haplotypes are. PMID- 2592020 TI - B-G cDNA clones have multiple small repeats and hybridize to both chicken MHC regions. AB - We used rabbit antisera to the chicken MHC erythrocyte molecule B-G and to the class I alpha chain (B-F) to screen lambda gt11 cDNA expression libraries made with RNA selected by oligo-dT from bone marrow cells of anemic B19 homozygous chickens. Eight clones were found to encode B-G molecules which hybridize with sequences in the chicken MHC as defined by congenic strains; the fusion proteins react with multiple immune but not preimmune sera, they select antibodies from the antisera to B-G, which then react with distinct erythrocyte B-G protein patterns, and they elicit antibodies from mice which in turn react with authentic B-G proteins. None of the clones represent a complete message, some--if not all- bear introns, and none of them match with any sequences presently stored in the data banks. The following new information did, however, emerge. At least two homologous transcripts are present in this homozygous chicken, thereby formally proving the existence of an expressed multigene family. The 3' ends (3'UT) are simple sequences with 80% nucleotide identity between clones, while the 5' ends (either coding or noncoding) are composed of multiple short repeats which are far less similar. These repeats could explain the bewildering variation in size of B G proteins within and between haplotypes. Southern blots of genomic chicken DNA gave complex patterns for most probes, with many bands in common using different probes, but few bands in common between haplotypes. The sequences detected are all present in the MHC, based on the congenic lines CB and CC. Most of these sequences map into the B-G region, but some map into the B-F/B-L region as defined by the haplotypes B15, B21, and their apparently reciprocal recombinants B21r3 and B15r1. PMID- 2592021 TI - Molecular cloning and chromosomal assignment of a human perforin (PFP) gene. AB - Human perforin cDNA was isolated and the complete nucleotide sequence of the gene determined. The deduced amino acid sequence of human perforin showed 68.4% similarity to that of mouse perforin. RNA blot analysis of the human perforin gene revealed that the gene product is expressed preferentially in killer-type cells among cell lines tested, and in large granular lymphocytes among the peripheral blood mononuclear cells. In situ hybridization analysis with a human perforin cDNA probe revealed that the human perforin (PFP) gene is located on chromosome 17q11-21. PMID- 2592022 TI - DNA sequences of mouse H-2 and Qa genes. PMID- 2592023 TI - Genomic sequence and organization of rabbit Tcrb constant region genes. AB - We previously reported that some rabbits have three different copies of T-cell receptor b (Tcrb) constant region genes unlike man, mice, and rats who generally have two copies. Two of these C beta genes were found on an approximately 14 kilobase (kb) and one on an approximately 6 kb Eco RI fragment. The gene on the 6 kb fragment is of beta 2 type. A previously described portion of the 14 kb fragment appeared to have sequences characteristic of C beta 1. We have now shown that the 6 kb fragment is adjacent to and 3' of the 14 kb fragment. Furthermore, the second linked sequence of C beta gene present on the 14 kb fragment resembles to a large extent the C beta 2 gene present on the 6 kb fragment. Moreover, this second C beta gene has a 5' cluster of J beta sequences resembling J beta 2 of other species. However, exon 4 and the 3' untranslated region (3'UT) are of the beta 1 type. Mapping studies using Southern analyses of both genomic DNA and the 14 kb clone have identified another cluster of J beta 2 sequences 5' of the third tandem C beta 2 gene present on the 6 kb Eco RI fragment. Thus, the second gene on the 14 kb fragment appears to be a chimeric genomic Tcrb gene that may have arisen by an unequal crossing-over event analogous to that which may have deleted C beta 1, D beta 2, and J beta 2 in NZW mice. PMID- 2592024 TI - Chymotrypsin treatment of HLA-A and B molecules reveals 1D-IEF variation. PMID- 2592026 TI - Abstracts of papers presented at the 30th annual conference of the Indian Society of Gastroenterology. Bangalore, October 5-8, 1989. PMID- 2592025 TI - Evidence for two new splits of HLA-B40. PMID- 2592028 TI - Oral cancer in the Indian population. PMID- 2592027 TI - Trace elements in the endometrium of infertile women. AB - Some essential trace elements were estimated in endometrium of regularly menstruating fertile women and in women with infertility due to cervical factors. The distribution of the trace elements zinc, copper, iron, selenium and manganese at any particular phase of cycle remains more or less semilier between control (i.e. fertile) and infertile (primary and secondary) subjects. PMID- 2592029 TI - Complications in 8793 cases of diabetes mellitus 14 years study in Bombay Hospital, Bombay, India. AB - Complications in 8793 hospitalised cases of diabetes in 14 years were present in 81.8 percent. It was equal in both sexes. They did not depend upon religious dietary habits or on economic condition/status of the patient. Hypertension was present in 42.2%. Ischaemic heart diseases in 27.2%. C.V.A. in 9.2% and gangrene and peripheral vascular diseases in 4.2%. Acute & chronic U.T.I. was in 31.4% and uraemia in 4.5% and K.W. Syndrome in 2.5%. In Infection Tuberculosis was in 5.9% and pyogenic skin infection in 4.1%. Vascular and renal complications increased with the duration of diabetes and with age in type II diabetes. PMID- 2592030 TI - Experimental pheohyphomycosis and mycotoxicosis by Curvularia lunata in albino rats. AB - A rice contaminating fungus 'Curvularia lunata' yields 'Curvularin', a potent mycotoxin. Experimental Pheohyphomycosis and Mycotoxicosis were observed in albino rats. Spore suspension produced localised lesion; with simultaneous steroid therapy produced lesion in distant organs. Mycotoxin, Curvularin, produced hepatic necrosis. PMID- 2592031 TI - Differential diagnosis of viral hepatitis based on hepatitis viral markers. AB - 192 patients of acute viral hepatitis (AVH) from three different hospitals of Madras metropolitan area during November 1985 to January 1986 were investigated for serologic markers of hepatitis A virus (anti HAVIgM) and hepatitis B virus (HBsAg, HBeAg, anti HBcIgM and anti HBs) by Enzyme linked immunosorbent assay (ELISA). While the overall pattern of AVH in Madras as revealed from the study showed Hepatitis A to be 36.4%, Hepatitis B 34.4% and Non-A Non-B 29.1%, the pattern differed significantly when areawise categorisation was done. The major AVH type in Government General Hospital was Hepatitis B (48.9%). While it was hepatitis A (46.9%) in Government Stanley Hospital and Non-A Non-B (40.0%) in Military Hospital. Using anti HBcIgM marker of Hepatitis B Virus and anti HAVIgM it was possible to make out that 13.5% of the cases, currently suffering from hepatitis A were either HBV carriers (8.3%) or cases convalescing from a previous Hepatitis B attack (5.3%). Various combinations of HBV markers positivity were observed and their diagnostic significance inferred. PMID- 2592032 TI - Serum copper and ceruloplasmin in pregnancy with anaemia. AB - Estimation of serum copper and ceruloplasmin was done in 25 non pregnant females, 25 healthy pregnant women followed from I to III trimester and 75 pregnant women with anaemia--25 in each trimester. Anaemia was further divided into mild, moderate and severe types (27, 32 & 16 cases respectively). Normal pregnancy was associated with progressive increase in serum copper and ceruloplasmin--values being highest in III trimester. All types of anaemias in pregnancy revealed statistically significant elevation of serum copper and ceruloplasmin when compared to corresponding gestational period in normal pregnancy. PMID- 2592033 TI - Rapid slide haemagglutination test in urinary candidiasis. AB - Quick diagnosis of urinary candidiasis was done by rapid slide haemagglutination test (SHA) and its efficacy was compared with countercurrent immunoelectrophoresis. This method was found to be much easier, less time consuming and an economical technique. Sera of 50 patients with urinary candidiasis were included for the present study and 50 control cases were also taken. The present study revealed that SHA test was more sensitive and specific than Countercurrent immunoelectrophoresis (the percentage of positive cases being 68% and 56% respectively). PMID- 2592034 TI - DNA ploidy with relation to histology in tumours of breast and rectum. AB - Biopsy materials from breast and rectal tumour cases were studied for cytophotometric analysis of DNA ploidy levels. Aneuploid DNA patterns were observed in majority cases of late stage and poorly differentiated carcinomas. Increased aneuploidy was also observed in metastatic growths and post menopausal cases of breast cancers. PMID- 2592035 TI - Mycetoma--epidemiological and pathologic study of 133 cases. PMID- 2592036 TI - Aging: relentlessly yours. PMID- 2592037 TI - REM sleep deprivation and food intake. AB - The effect of REM-sleep deprivation (REM-SD) on diet preference was studied in rats. REM-SD for a period of 72 hrs produced an increase in day, night and 24 hrs (day plus night) intakes of Carbohydrate Rich diet (CRD) and Total diet (TD). Body weight (BWt) was also increased. The maximum increase in the above parameters were recorded on the 2nd day of REM-SD. During recovery period the intakes of TD fully recovered, but the BWt and consumption of CRD remained high. Intakes of Balanced diet (BD) remained significantly on the lower side when compared to the pre REM-SD mean values. During REM-SD, the rats preferred CRD than BD. The body temperature did not show any change. The increase in TD intake and BWt could be the result of an increase in insulin level and the change appears to be mediated by the activation of hypothalamic feeding centre. PMID- 2592038 TI - Modification of the antihypertensive effect of indapamide by indomethacin. AB - Oral treatment with indapamide was found to reduce blood pressure of hypertensive rats but not of normotensive rats. Chronic indomethacin treatment had no effect on blood pressure of untreated normotensive and hypertensive rats. Also indomethacin did not modify the antihypertensive effect of indapamide excluding the direct involvement of PGs in the antihypertensive effect of indapamide. Vascular reactivity to pressor agents NA, ADR and ANG was significantly increased after indomethacin treatment. This may be due to the blockade of the actions of PG in modifying vascular reactivity to vasoconstrictor agents or may be a direct effect of indomethacin on calcium fluxes. Indapamide reduced the reactivity to NA and ANG in the presence of indomethacin suggesting that the antihypertensive effect of indapamide may be through a decrease in reactivity to pressor agents which is independent of increase in the synthesis of vasodilator PGs. PMID- 2592040 TI - Pulmonary functions of the elderly Indian subjects: trends of decline with age. AB - Respiratory Functions mainly vital capacity, FEV1, MBC and breath holding time, of 400 healthy elderly persons, 328 men and 72 women, aged 60+, sedentary and belonging to upper middle class from Bombay were studied. The findings are examined in each sex in 5 yearly age groups and are obviously low. An attempt is made to link the age-wise averages of VC in younger subjects in India reported by other workers with our data on elderly. The values from Northern groups are comparatively much higher than those from the rest of India. The connecting link in graphs shows a sudden fall when the data of northern Indians and that of our elderly are joined, but it is smooth when those of rest of India are connected. PMID- 2592039 TI - Brain biogenic amine levels after methanol administration: possible mechanism of action on central monoaminergic neurons in discrete areas of brain in Wistar rat. AB - Alterations in the steady state level of rat brain biogenic amines - dopamine, nor-epinephrine, epinephrine, serotonin and 5-hydroxy indole acetic acid, in response to intraperitoneal administration of methanol (3g/kg b.w.) were studied in discrete areas of the rat brain. The monoamine changes induced by methanol were quite different from those induced by ethanol consumption. They were also region-specific; hypothalamus being more vulnerable for methanol-induced monoamine changes. The effects produced by methanol were correlated with the blood and brain level of methanol at the given time, suggesting that the effects were dependent upon the local concentration of methanol in different brain regions. Acidosis induced by ammonium chloride and sodium formate administration did not alter the monoamine levels and therefore, the effects of methanol were not possibly due to acidosis. Blocking or delaying the metabolism of methanol either by 4-Methyl Pyrazole and 3-Amino 1,2,4-Triazole or by simultaneous administration of ethanol resulted in the potentiation of methanol effect. Therefore, it was concluded that methanol induced changes in brain biogenic amines were due to methanol per se and not due to metabolic end products viz. formaldehyde or formic acid. PMID- 2592041 TI - Effect of glucose electrolyte ingestion on physiological changes due to severe heat stress. AB - Severe heat stress experienced by aircrew during summer months can cause deterioration in performance. Acute heat stress can also lead to dehydration and loss of electrolytes. Previous studies emphasised the need of K+ replacement. This study was carried out to determine the effect of glucose electrolyte ingestion (ELECTRAL) on thermal strain parameters. Ten healthy male subjects in the age group of 19-43 years were exposed to an acute thermal environment of 50 degrees C Tdb with relative humidity of 30% for 40 min. twice each day on two different days with an interval of one hour in between the exposures. At the beginning of rest period electrolyte solution was ingested during electrolyte trials and water under control trials. Physiological parameters of Tsk, T or, HR and electrolyte concentration of Na+ and K+ in sweat did not show any significant difference in both the trials. Sweat loss was significantly higher during electrolyte trials. PMID- 2592042 TI - The study of tasters and non-tasters of phenyl-thio-carbamide (PTC) and its relation to blood groups. AB - The ability to taste phenyl-thio-Carbamide (PTC) is one of the gene marker systems which provides one of the means to reconstruct relationships of ethnic groups of man. In 433 Maharashtrian subjects the ability to taste PTC was studied by Harris and Kalmus method. At the same time, blood groups of these subjects were determined by slide agglutination method. It was found that 63.74% of local population was taster and 36.26% non-taster. The percentage of non-tasters was higher in males, than in females. No significant relation was found between the ability to taste PTC and the blood groups. The results were compared with those observed by other workers and it was found that the percentage of non-tasters in local population in the present study was similar to that found in Indian elsewhere. PMID- 2592043 TI - Effects of cimetidine combination with cyclophosphamide in transplanted murine tumors. AB - Studies were carried out on the combination of Cimetidine (CMTD) with Cytoxan (CTX) in three murine tumors. While the combination significantly potentiated the anticancer effect of CTX in L1210 leukemia, the results with P388 leukemia were not significantly different. The results with Lewis Lung Carcinoma showed a consistent reduction in the number of metastases. However, there was no consistent concomitant prolongation in survival. The host strain, biology of the tumour and the drug used in combination with CMTD might be some of the factors responsible for the varied response. PMID- 2592045 TI - Effect of inspiratory and expiratory air flow on congestion and decongestion in the nasal cycle. AB - The role of the inspiratory and expiratory airflow through nostrils during the process of breathing in the reflex reciprocal congestion and decongestion of the nasal cycle was examined in this study. Air flow through each nostril was measured separately in male subjects before and after four types of breathing practices for 15 min each consisting of (1) inspiration through the patent nostril and expiration through the congested nostril, (2) inspiration through congested nostril and expiration through patent nostril, (3) inspiration through both nostrils and expiration through mouth and (4) inspiration through mouth and expiration through both nostrils. The breathing practices had no effect on the congested nostril but caused decrease in air flow through the patent nostril, indicating congestion. It is suggested that the inspiratory and expiratory air flow through the nostrils caused reflex congestion of the patent nostril. The stimuli arising from the nasal mucosa due to air flow during breathing may form the basis for the reflex reciprocal congestion and decongestion of nostrils in the nasal cycle. PMID- 2592044 TI - Effect of immobilization stress on food intake, body weight and weights of various organs in rat. AB - Effect of immobilization stress was studied in male albino rats. Experimental rats (E) were restrained in close-fitting wiremesh cylinders. Control rats (C) were not subjected to restraint. Food and water were made available to C for all the 24 hrs while the E were given them for only 6 hrs daily. The initial lower food intake of E was later reversed to near normal levels. There was a steady fall in the body weights of E, while the C displayed a normal growth rate. Cerebrum, cerebellum, pituitary and adrenals of E weighted significantly more. There was an apparent increase in the weight of thyroid. Gonads displayed no change in weight. The results indicate that chronic restraint causes loss of body weight inspite of a near normal food intake. It also produces an increase in the weight of brain, and certain endocrine organs. PMID- 2592046 TI - Determination of %FVC (FEV/FVC%) at expiratory flow rate of 1 lit/sec and 0.5 lit/sec from forced expiratory spirogram. AB - A method for determination of %FVC (FEV/FVC%) at forced expiratory flow rate (FEF) of 1 lit./sec. and 0.5 lit/sec from the forced expiratory spirogram is described. This parameter is simpler to determine and is a better expression of end expiratory flow rate than FEF 75%-85%. PMID- 2592047 TI - A comparative study of the hypoglycemic action of the seeds and fresh leaves of Ocimum sanctum (Tulsi). PMID- 2592048 TI - Effects of nitroxazepine on guinea-pig isolated detrusor and trigone muscles. PMID- 2592049 TI - [Cervico-facial cutaneous fistulas of dental origin. Development-treatment]. PMID- 2592050 TI - [How to save time and money without compromising the quality of care]. PMID- 2592051 TI - [Time spent by Lorraine general practitioners in prophylactic periodontal care]. PMID- 2592052 TI - [Radiographic study]. PMID- 2592053 TI - [Welcome to the dental office]. PMID- 2592054 TI - [Subgingival administration of antimicrobials in periodontology. Update]. PMID- 2592055 TI - [Dental caries ... a declining disease]. PMID- 2592056 TI - Assessment of probability of survival in penetrating injuries using the TRISS methodology. AB - By the TRISS methodology, probability of survival in injury can be estimated. It is based on a statistical analysis of outcome which is influenced by the severity of the injuries as expressed in the Injury Severity Score (ISS), the physiological function as expressed in the Trauma Score (TS) and the patient's age. We have used the TRISS formula in 206 patients with penetrating injury. Of these patients, 149 sustained stab wounds, 32 gunshot wounds and 25 others. ISS ranged from 2 to 38, the mean ISS being 9. The function was good (TS greater than 14) in 85 per cent. Estimated probability of survival ranged from 1.00 to 0.42. Three patients (1.5 per cent) died. The probability of their survival was 0.92, 0.96 and 0.98, respectively. All the fatal cases had serious predisposing conditions: chronic pulmonary disease, alcoholism, and psychiatric illness. In penetrating injury, the patient's functional status at the start of treatment is of greater importance for the outcome than the anatomical severity. The concept of the methodology of TRISS for assessment of probability of survival seems useful for review and comparison in injury care. PMID- 2592057 TI - Human immunodeficiency virus and hepatitis B virus in injured patients and victims of violence. AB - Of a total number of 643 injured patients admitted during 1986 and 1987, 113 were tested for antibodies against the human immunodeficiency virus (HIV) and hepatitis B surface antigen HBsAg and the concentration of hepatitis B surface antibodies (HBsAb) was determined. Nine patients were HIV positive while HBsAg was detected in two patients and increased levels of HBsAb were found in 19 patients. HIV antibodies were found in 6 (4.8 per cent) of 124 victims of violence, in 3.3 per cent of the patients with penetrating injuries and 1.1 per cent of the patients with multiple, closed injuries. The estimated prevalence for HIV infection in the Norwegian population is 0.08 per cent, thus indicating an over-representation of infected patients among injured patients and victims of violence. PMID- 2592058 TI - Invalidity of speculated injury mechanism in autopsy reports. AB - Postmortem and crash investigation reports were examined for 35 cases of belted automotive crash fatalities. This paper highlights those cases with speculation of the injury mechanism in the post mortem report. In two cases, the medical examiner made specific reference to a 'whiplash' mechanism of brain injury, which refers to an inertial loading of the neck without head contact. Examination of the car interior in one case indicated evidence of head contact with transfer of hair, and the other facial contact with transfer of teeth. Death was more likely due to direct head impact. In another case, the vehicle was struck laterally by another car on the far side of the driver. The medical examiner stated that the driver incurred typical 'steering wheel type' injury, while examination of the car interior indicated no consequential contact between the driver and the steering wheel. Instead, the intruding passenger door probably impacted the driver at a velocity high enough to induce fatal chest injuries. These cases demonstrate the necessity of a thorough examination of contact points in the crashed car to discern the mechanism of injury and to reconstruct the kinematics of injured occupants in a crash. They also demonstrate how 'popular' misunderstanding of mechanisms of fatal injury may be introduced and perpetuated. PMID- 2592059 TI - Sharp thoracic injury. AB - In an effort to develop effective rules for the management of penetrating thoracic injuries, all records of 515 patients treated for sharp chest injuries between 1961 and 1985 at the University Hospitals of Amsterdam (Binnengasthuis, Wilhelmina Gasthuis and Academic Medical Centre), were reviewed. The analysis reveals that of these patients 321 (62 per cent) could be treated conservatively, because of a non-penetrating injury, while 140 had a penetrating injury, of whom 77 had to be operated on. Eleven patients died (2.1 per cent). Data concerning these patients are discussed separately. Based on our analysis, and supported by recent literature, an aggressive approach towards penetrating thoracic injury in haemodynamically unstable patients is justified. PMID- 2592060 TI - Do we need to cross-match blood in closed fractures of the shaft of the femur? AB - A total of 50 patients with isolated closed fractures of the shaft of the femur are presented. Eleven per cent of the blood specimens were merely grouped and saved on arrival, and the remaining 39 (78 per cent) were crossmatched between 2 and 6 units. Overall, 138 units of blood were crossmatched and only 16 units were used (11.5 per cent), none of them actually in the accident and emergency department. We can find no record of blood being given for resuscitation. The use of blood appeared to depend on the occurrence and timing of operation. We suggest that local policy for crossmatching blood for such patients takes into account the orthopaedic surgical plan, but that the routine instruction to cross-match blood on arrival be abandoned. PMID- 2592062 TI - How successful is below-knee amputation for injury? AB - This study analyses how successfully young adults rehabilitate after below-knee amputation for injury. Twenty-five patients referred to Bristol Artificial Limb and Appliance Centre and aged under 45 years at the time of amputation were investigated 2-12 years after operation by a review of their records, a questionnaire and, in a few cases, by interview. Most did extremely well. All without serious disabilities were able to work, most requiring little or no sick leave because of their amputations. Prostheses were worn by 84 per cent of patients for more than 13 h a day and only 32 per cent had left them off for more than 4 days in the previous 12 months. One mile could be walked by 72 per cent, nearly all (84 per cent) drove cars, and the majority could use public transport with relative ease. Of the patients 84 per cent regarded themselves as only slightly or not at all disabled. However, it takes about 1 year to reach this satisfactory 'present state' and 72 per cent remain troubled by phantom limb or stump pain. PMID- 2592061 TI - Transposition of the semitendinosus tendon for early repair of medial and anteromedial laxity of the knee. AB - In 15 patients with acute medial (N = 8) or anteromedial (N = 7) laxity of the knee, reconstruction of the torn ligaments was combined with the use of the semitendinosus tendon as a dynamic extra-articular stabilizer. The postoperative regimen consisted of early mobilization in a mobile cast with full weight bearing. An evaluation 1 to 3 years after surgery revealed good results in 14 cases, and one fair result as graded using the Marshall score (mean score 45.3, SD 2.9). Isokinetic measurements of knee flexion and extension showed no loss of strength. Equally good results have been reported in conservatively treated isolated MCL lesions. In case of a combination of a MCL lesion and an ACL lesion the results reported are usually worse. This treatment regimen seems to be a good concept in acute anteromedial laxity of the knee and cannot be considered anything but an alternative in isolated MCL lesions. PMID- 2592064 TI - Rupture of the deltoid ligament in ankle fractures: should it be repaired? AB - In the 2 years after January 1984 we treated 290 fractures of the lateral malleolus in adults, 169 (58 per cent) of them operatively according to the AO ASIF principles. In 28 fractures (10 per cent) there was also a rupture of the deltoid ligament. These patients were all operated upon, without exploring the medial side of the ankle joint. Postoperative treatment involved movements and partial weight bearing for 6 weeks. These 28 patients were reviewed after an average interval of 18 months. The Weber scoring system was used to assess the results. In 20 cases there was a very good or good result. In eight cases the result was poor. No patient had any sign of medial laxity either clinically or on eversion-stress radiographs. Some patients had signs of osteoarthritis. CLINICAL RELEVANCE: After anatomical reconstruction of the lateral malleolus with perfect congruity of the ankle mortise there is no need to explore and suture the ruptured deltoid ligament. After rigid internal fixation of the lateral malleolus postoperative treatment can allow full function. PMID- 2592063 TI - Serum osteocalcin and total alkaline phosphatase levels as prognostic indicators in tibial shaft fractures. AB - Serum samples were obtained periodically from 50 adult patients with closed tibial shaft fractures. Total alkaline phosphatase activity was measured in all cases and osteocalcin activity was measured in 14 patients. Fractures produced by high-energy violence generally had lower values of osteocalcin activity. This could be due to depressed circulating vitamin K levels throughout the healing period in the former fractures. In addition, normally uniting fractures had generally higher values of osteocalcin activity compared with fractures exhibiting delayed union. This indicates depressed osteoblastic activity in slowly healing fractures. The results suggest that measurement of osteocalcin activity after fracture could provide a useful prognostic indicator. By contrast, total serum alkaline phosphatase activity was not significantly different between the injury groups and between the healing groups. PMID- 2592065 TI - Radiological assessment of atlanto-axial injuries. AB - Injury to the cervical spine is a potentially lethal condition, and the accurate detection of such injury is essential. Plain cervical radiography remains the first line of investigation, despite well documented difficulty with interpretation. There have been many studies demonstrating unreliability of plain cervical radiography in detecting atlanto-axial injuries. We report a group of patients in which false-positive interpretation of such injuries occurred. PMID- 2592066 TI - Tension pneumopericardium following stab wounds to the chest: report of two cases. AB - Two cases of tension pneumopericardium following stab wounds to the chest are reported. The first presented with delayed onset respiratory distress and a precordial systolic murmur, and was treated by thoracotomy. The second presented with acute cardiac tamponade and was treated by needle aspiration. The clinical and radiological features of tension pneumopericardium and its treatment are reviewed. PMID- 2592067 TI - Locking of posterior process of talus in the sulcus calcanei in a case of peritalar dislocation. PMID- 2592068 TI - Employment after severe head injury: do the Manpower Services Commission schemes help? AB - This paper describes the use of Manpower Services Commission (MSC) employment rehabilitation schemes by a series of severely head injured people. Most of those who achieved employment did so without making use of MSC schemes. A majority of those using MSC schemes remained unemployed at last follow-up. Those attending MSC schemes were more likely to have been in education at the time of injury. Some of those previously in work used schemes, but only after they had already failed at work or had had a long period out of work. MSC schemes may fail to meet the needs of the head-injured because many are too short or use is made of them at too long an interval after the injury. They do not cater well for special training and the flexible approach that is necessary for successful employment rehabilitation of those suffering from brain injury. The priority is for training schemes that can be carried out within the workplace and for support and incentives to employers to help head-injured people return to their previous work. PMID- 2592069 TI - Traumatic rupture of a renal angiomyolipoma. PMID- 2592070 TI - Posterior dislocation of the elbow with an osteochondral fracture. PMID- 2592071 TI - Interposition of the dorsal interosseous tendon in a fracture of the base of the proximal phalanx of the right ring finger. PMID- 2592072 TI - Bath centre-hole canvas for hip fracture table. PMID- 2592073 TI - Significance of urgent (within 6h) internal fixation in the management of fractures of the neck of the femur. AB - The value of internal fixation of fractures of the neck of the femur within 6 h was assessed in a review of a 3-year series. Three groups were compared, in which the operation was performed within 6 h, between 6 and 24 h and after 24 h respectively. The time and quality of union and the incidence of collapse of the head of the femur were significantly better in the first group. The difference in the results between the other two groups was not significant. In view of these data the authors recommend the internal fixation of fractures of the neck of the femur within 6 h. PMID- 2592074 TI - Treatment of subtrochanteric fractures of the femur: a study of intramedullary compression nailing. AB - The results of prospective treatment of 31 patients with subtrochanteric fractures using the Derby intramedullary nail are presented. The nail design, plus cerclage wires in unstable cases, allows axial compression of the fracture, to give rigid fixation and load-sharing between bone and nail. Twenty-seven patients were followed up for an average of 21.7 months. There were no mechanical failures of the nails, and all 27 fractures united, two in minimal varus. Relatively early mobilization of the patients with isolated fractures occurred. PMID- 2592075 TI - Epiphyseal fractures of the proximal tibia. AB - During a 12-year period there were 15 patients with proximal tibial epithyseal fractures. Eleven were examined at follow-up with a mean observation time of 7 years (range 3.5-12.5). Five patients with type IV or type V lesions had concomitant avulsion fractures of the tibial insertion of the anterior cruciate ligament, two being displaced. Eight out of twelve patients had concomitant ligamentous injuries. At follow-up two patients complained of instability, confirmed by clinical examination. Another two patients had symptom-free anterior laxity. Serious angular deformity was found in two patients, while important leg length discrepancy was observed in one. Degenerative changes of the knee joint were found in three patients. An active reconstructive approach is recommended, and attention is drawn to concomitant ligamentous injuries which, it seems, in the past have tended to be underestimated. PMID- 2592076 TI - Impingement of vascular pedicles by external fixator pins. AB - Three cases of impingement of external fixator pins on vascular pedicles which complicated microvascular reconstruction of severe leg injuries are presented. Recommendations concerning pin placement are made. PMID- 2592077 TI - False aneurysm of the superficial femoral artery associated with fracture of the femur. PMID- 2592078 TI - Isolated dislocation of the tarsal navicular. AB - An unusual case of isolated dorsal dislocation of the tarsal navicular bone due to hyperextension of the foot is presented. The treatment was closed reduction with percutaneous fixation with a Kirschner wire and immobilization for 8 weeks. The end result was satisfactory. To prevent redislocation leading to arthritis, the Kirschner wire should be left in place for at least 6 months. PMID- 2592079 TI - Double fractures of AO intramedullary femoral nails. AB - We report two cases of double fractures of AO intramedullary femoral nails, with metallurgical analysis of one of the nails. Technical errors were noted in both cases and in these circumstances careful assessment of fracture union is required because double fracture can lead to potentially difficult revision surgery. PMID- 2592080 TI - Accident services re-viewed: a comment on the report of the working party of the Royal College of Surgeons of England on 'The Management of Patients with Major Injuries'. PMID- 2592081 TI - A review of fatal road accidents in Oxfordshire over a 2-year period. AB - The records of 131 road accident fatalities which occurred in Oxfordshire over a 2-year period were reviewed. Aspects of the accident circumstances, the injuries incurred and the cause of death were examined. The majority of fatal accidents occurred during daylight hours and in dry weather. Deaths were mainly due to cerebral injury (34.4 per cent) or uncontrollable (mainly thoracic) haemorrhage (25.2 per cent), or a combination of both (8.4 per cent). A number of deaths occurred in hospital from complications rather than from the injury itself. In addition to this, there were four deaths from natural causes. Where death occurred at the scene of the accident, blood alcohol levels were determined. Almost 50 per cent of the drivers for whom a level was obtained had measurable alcohol in their bloodstream, and 28 per cent of such drivers were over the legal limit. Three cases who reached hospital alive were, on review, assessed to have potentially survivable injuries, and a further two patients died in the post accident period of potentially survivable complications. PMID- 2592082 TI - Preventability of death from penetrating injury in England and Wales. AB - A total of 1000 deaths from injury in England and Wales have been reviewed to establish the incidence and pattern of penetrating injury and the adequacy of its management. Of the 1000 deaths, 71 (7.1 per cent) were due to penetrating injury. There were 32 knife wounds and 30 firearm injuries. Most of the latter were suicides. Only 17 patients (24 per cent) reached hospital alive. Of these cases, 10 had extracranial injury and all 10 deaths were considered to have been potentially preventable when reviewed by four external assessors. One of seven patients with cranial injury was considered to have been a potentially preventable death. The median age of the 11 cases of potentially preventable death was 37 years (range: 7-61 years). Of these, three did not have any surgery for surgically treatable injuries. Seven patients underwent operation and difficulty was encountered in six of these. It appears from our figures that whilst penetrating injury is an uncommon cause of death, it is poorly managed. The implications of this finding for systems of injury care in the United Kingdom are discussed. PMID- 2592083 TI - Factors affecting the prognosis of multiply injured patients: an analysis of 1169 consecutive cases. AB - When analysing 1169 multiply injured patients treated in the intensive care unit between 1966 and 1984 we noticed a dramatic fall in mortality from a level of about 14.6 per cent to 4.8 per cent since 1981. The patient populations and accident patterns were surprisingly identical, though since 1981 the severity of thoracic injuries has increased and the brain injuries decreased. The fall in mortality was great for all causes of death but most significant for patients with severe thoracic, brain and cervical spine injuries. The trend is to treat more and more fractures operatively and immediately after the injury. There has been a better diagnosis of all injuries according to autopsy findings. An attitude of prophylactic treatment on a respirator which leads to better oxygenation, together with a well-organized, co-ordinated injury care system with systematized diagnostic, laboratory and therapeutic procedures, are among the most important factors in the lowering of the mortality. PMID- 2592084 TI - Compression-fixation of long bone fractures: problems and pitfalls revisited. AB - We have carried out a retrospective study, over a 2.5 year period, of the results of compression-fixation for diaphyseal long bone fractures (forearm 49, tibia 18, others 9). The method was used in forearm fractures mainly for fresh fractures, whilst in fractures of the tibia it was predominantly for delayed union. In forearm fractures, although 10 per cent showed failure of fixation, only 2 per cent developed infection, and 90 per cent recovered a full range of movement. Conversely, plating of fractures of the tibia with delayed union resulted in a 37 per cent deep infection rate. It is concluded that while compression-fixation gives excellent results when applied to displaced forearm fractures, alternative methods should be used in fractures of the tibia with delayed union. This unexpected finding illustrates the value of periodic audit of surgical results. PMID- 2592085 TI - Spinal cord injury: prognostic indicators. AB - A retrospective analysis of 70 patients with closed traumatic incomplete injuries of the spinal cord was performed. Of those presenting with motor sparing, as minimal as muscle flicker, 86 per cent recovered useful motor function. Of those presenting with spinothalamic sensory sparing, as minimal as unilateral sacral sparing, 71 per cent recovered to a similar functional level. While the patients presenting with preservation of only posterior column sensory sparing had the worst prognosis, some still showed important improvement. Meticulous neurological assessment within 72 h of the injury can localize the tract spared and can help with the prognosis in those patients with incomplete lesions. PMID- 2592086 TI - Traumatic diaphragmatic hernia: review of 15 cases. AB - From January 1985 to December 1987, 292 laparotomies were performed for injury in Riyadh Central Hospital. Of these, 15 cases were associated with diaphragmatic injuries (5.1 per cent). The diagnosis was missed in 5 cases (30 per cent) and was incidental (at laparotomy) in 3 cases (20 per cent). Therefore in about 50 per cent of the cases, the diagnosis was not made at the initial presentation. In this paper we stress the importance of maintaining a high degree of clinical suspicion in order not to miss traumatic diaphragmatic hernia in multiply injured patients. PMID- 2592087 TI - Free flap cover of acute hand injuries. AB - Eighteen free flap reconstructions of acute hand trauma were compared with 12 groin flap repairs as historical controls. The free flap group had a similar success rate, with fewer operations (though the same total operating time) and shorter hospital stay than the groin flap group. Complications were the same in both groups, but less secondary procedures were necessary in the free flap group. If flap cover is necessary, free flaps are a better way of obtaining skin cover in acute hand trauma. PMID- 2592088 TI - Implant failures in patients with proximal fractures of the femur treated with a sliding screw device. AB - A review of 385 proximal fractures of the femur treated with a telescopic screw system revealed that in nine cases the device had cut out of the head of the femur necessitating its removal. In two cases the head of the femur had been penetrated at the time of insertion. In all but one of the remaining seven cases the screw had been inserted in the superior half of the head and neck of the femur. The overall cut-out rate was 2.25 per cent but was 11.9 per cent when the screw was placed in the superior half of the head. When the screw was placed in the inferior half of the head, the cut-out rate was only 0.29 per cent. There was no correlation between this mechanical failure and age, sex, type of fracture or the presence of metabolic bone disease. These results indicate that if this otherwise effective form of internal fixation is to be used in the treatment of proximal fractures of the femur, care must be taken to avoid placement of the device in the superior half of the head and neck of the femur. PMID- 2592089 TI - Performance of horse-riding helmets in frontal and side impacts. AB - Cases of head injury are reviewed in which riders wearing jockey skull caps have suffered impacts to the front, back or side of their helmets. The design and constructional materials of such helmets are assessed. Impact tests that simulate the accidents confirm the low energy absorption potential of some helmets for lateral impacts. Most pedal or motorcycle helmet designs afford better lateral impact protection. PMID- 2592090 TI - Post-concussional symptoms following minor head injury. AB - The effect of admission to hospital after a minor head injury on the incidence and duration of post-concussional symptoms was investigated. A total of 114 adults with a minor head injury were randomly allocated to admission for 24 h or to discharge from the accident department. Follow-up was by postal questionnaire. This revealed that 90 per cent of patients suffered symptoms lasting an average of 2 weeks. The patients who were discharged had symptoms that lasted a shorter time. Admission to hospital does not reduce the incidence and severity of symptoms following minor head injuries in adults. PMID- 2592091 TI - Treatment of displaced fractures of the proximal humerus: transcutaneous reduction and Hoffmann's external fixation. AB - Experience with transcutaneous reduction and external fixation of displaced fractures of the proximal humerus is presented in a series of 28 cases followed for 1 year or more. In 18 cases near-anatomical fracture reduction was obtained, while no improvement of fracture position was seen in two cases. Loosening of the pins was a major complication in five cases, all in patients with severe osteoporosis or head splitting fractures, where fracture reduction was unsatisfactory. The functional results were satisfactory, and the method is considered a useful alternative in the treatment of these difficult fractures. PMID- 2592092 TI - Spontaneous rupture of the flexor pollicis longus tendon: a report of three cases. PMID- 2592093 TI - Ipsilateral supracondylar fracture of humerus and forearm bones in children. AB - A total of 34 children with ipsilateral supracondylar fractures of the humerus and forearm were studied over an 8-year period. Of these, 19 patients had fractures of the distal quarter of the forearm bones while eight patients had a distal radial epiphyseal injury. Five of the patients had undisplaced supracondylar fractures. One patient had an anterior supracondylar fracture. All forearm fractures were treated by closed reduction. Nine displaced supracondylar fractures which could not be reduced by closed manipulation were treated by olecranon pin traction in two cases and by percutaneous pinning in seven cases. Excellent or good results were found in 29 children after an average follow-up of 3.8 years. PMID- 2592094 TI - Stability assessment of distal radius fractures. AB - A total of 112 consecutive cases of fractures of the distal radius managed conservatively were graded according to radiological criteria using the first radiograph. These criteria, as well as age over 60 years, were considered as gravity factors. A strong correlation was found between these criteria and the risk of secondary displacement, despite a correct initial reduction. PMID- 2592096 TI - Penetrating bile duct trauma. AB - Two patients who sustained penetrating extrahepatic ductal injuries are presented. The two uncommon injuries described respectively illustrate the relative simplicity and complexity which may be involved in their diagnosis and management. Accurate recognition and appropriate primary repair of a partial common hepatic duct injury led to an uncomplicated outcome. Failure to recognize a confluence injury led to recurrent complications, intensive investigation and a difficult but successful late reconstruction. PMID- 2592095 TI - Retrospective analysis of plate fixation of diaphyseal fractures of the forearm bones. AB - A total of 133 fractures of the forearm bones treated by stainless steel plating have been reviewed. Technical error is the main cause of non-union. Although a union rate of 94.7 per cent was achieved, closer examination of the material shows that the stability of fixation is important in achieving early consolidation. PMID- 2592097 TI - Staples versus sutures in the closure of scalp wounds: a prospective, double blind, randomized trial. AB - Over a 6-month period, patients attending the Accident and Emergency Department of the Mater Infirmorum Hospital with scalp wounds were randomly allocated to one of two groups for closure of their wounds with either nylon sutures or metal staples. Each group contained 100 patients. Patients were reviewed at 5 days (95 per cent) after the removal of sutures or staples and again at 3 weeks (61 per cent). The two groups were similar for age, sex, aetiology and wound characteristics. There was no difference in morbidity or rate of wound infection but stapling was significantly faster and less painful. The use of staples carries no risk of accidental needle-stick injury and should therefore be safer than suturing for the user. PMID- 2592098 TI - The Bath bridge angle-guide. AB - A device is described which facilitates the accurate location of a guide-pin for the placement of the sliding lag screw when treating fractures of the subtrochanteric zone of the femur with any of the modern sliding hip screw plates. PMID- 2592099 TI - Technical considerations of the AO interlocking nail. AB - We report 23 patients treated with 24 AO femoral intramedullary locked nails performed at the John Radcliffe Hospital, Oxford. There were no major complications and all 17 acute traumatic fractures followed up for longer than 4 months proceeded to an uncomplicated union, with an excellent range of knee movement. PMID- 2592101 TI - Sliding hip screws: modes of failure. AB - The modes of failure of the sliding hip screw devices were investigated by reviewing 223 cases. There were 35 mechanical failures. Two of these occurred when the components separated in highly comminuted fractures. The use of the locking screw is recommended to prevent this. The other 33 occurred when the device had lost its sliding action. The reasons for this included jamming, insufficient slide being available and additional fixation. To reduce the complication rate it is recommended that any additional fixation (such as cerclage wires) should be used with care to ensure that they do not block the barrel. For patients with short femoral necks, a shorter barrelled version of the device should be used as it would have a greater sliding capacity. Guidelines for its use are given. PMID- 2592100 TI - Simple traction system for closed intramedullary nailing of the tibia. AB - A simple traction system which facilitates closed intramedullary nailing of the tibia is described. The system is easy to erect and uses equipment which is readily available in most operating theatres. PMID- 2592102 TI - Post-traumatic oedema of the foot after tibial fracture. AB - A total of 97 patients with diaphyseal tibial fractures treated with functional bracing were studied prospectively. Persistent ipsilateral foot swelling was present in 84.5 per cent of the patients. Most of the swellings subsided with time, but a small percentage of them persisted for a duration of 2 years or more after injury. The time for disappearance of the swelling in 50 per cent of the patients was 18.6 weeks. The development of oedema is not related to the age and sex of the patients, the configuration, type and level of the fractures, or the association of a fibular fracture. The bone healed quicker in those who did not have swelling of the foot. Once the swelling has developed, it seems to run its own course and its disappearance is not related to the age and sex, the configuration, type and level of fractures, the association of a fibular fracture, or the time for fracture healing. This complication does not have any adverse effect on the functional recovery of the patients. PMID- 2592103 TI - Extradural haematoma associated with essential thrombocythaemia in a child after a relatively minor head injury. PMID- 2592104 TI - Tracheal shift in cervicothoracic dislocation. PMID- 2592106 TI - The upside-down radial head: brief report. PMID- 2592105 TI - Brachial artery entrapment in closed elbow dislocation. PMID- 2592107 TI - An unusual forefoot dislocation. PMID- 2592108 TI - Traumatic separation of a bipartite patella. PMID- 2592110 TI - Autonomic function and anesthesia. PMID- 2592109 TI - Hungerford shooting incident. PMID- 2592111 TI - Polymorphonuclear leukocyte stimulation measured by phage inactivation. AB - A quantitative assay for determining the polymorphonuclear neutrophil (PMN) stimulation is described. The method is based on the inactivation of lambda vector phages that occurs after a brief exposure to stimulated PMNs. The determination of the number of residual plaque-forming units on the appropriate bacterial host allows a reproducible and sensitive quantitative assay for measuring the stimulation level of the PMN. In comparison with other methods that employ bacteria or eukaryotic cells, this assay provides several advantages and can be used for investigating the biochemical and physiological processes responsible for PMN stimulation. PMID- 2592112 TI - Investigation of the allergenic activity of isolated fractions of a standardized partly purified whole mite body (Dermatophagoides pteronyssinus) extract. AB - Twelve fractions of a molecular weight range of 1.35-670.00 kilodaltons (kD) were isolated from a biologically standardized partly purified whole mite body extract (Dermatophagoides pteronyssinus) by preparative size exclusion high-performance liquid chromatography. The allergenic activity and the antigen and allergen patterns of the isolated fractions were investigated by RAST, RAST inhibition and crossed (radio)immunoelectrophoresis (CIE/CRIE). By CRIE, each of the fractions showed allergen patterns, mostly of different compositions. Each fraction showed allergenic activity of different degrees by RAST inhibition. The highest allergenic activity could be measured by RAST inhibition with fractions which contained predominantly the major allergens Der pI and PY as detected by CRIE. Also proteins of higher molecular weights (greater than 158 kD) showed IgE binding capacities. Nearly all antigens detected by CIE could be identified as allergens using CRIE. PMID- 2592113 TI - Identification and partial characterization of a T-cell-derived antigen-binding factor from mice infected with the intestinal helminth Trichinella spiralis. AB - Immunochemical and biological characterization was performed of an antigen binding factor derived from culture supernatants of T cells from mice infected 4 days previously with the intestinal helminth Trichinella spiralis. Affinity chromatography with T. spiralis antigen resulted in the purification of a protein, provisionally designated Trichinella factor (Tric-F), that shared antigenic and other properties with a known T-cell-derived antigen-binding factor of different antigenic specificity, picryl chloride factor, which mediates an early 2-hour component of contact sensitivity. Tric-F lacked determinants of immunoglobulins and possessed determinants shared by other antigen-specific T cell factors, as determined by ELISA and antibody affinity chromatography. Biological activity of Tric-F was assayed in vivo and in vitro. Mice injected intravenously with Tric-F developed an antigen-specific early 2-hour ear swelling response following local challenge with T. spiralis antigen. These results corresponded to delayed-type hypersensitivity responses in the ears of T. spiralis-infected mice that comprised early 2-hour and late classical 24-hour responses. In vitro, Tric-F induced serotonin release by mast cells in the presence of T. spiralis antigen. Mast cells sensitized with Tric-F formed rosettes with antigen-coated sheep erythrocytes. It is suggested that Tric-F, an antigen-binding molecule that is T-cell-derived, mediates the early 2-hour component of delayed-type hypersensitivity and is involved in the initiation and regulation of T-cell-mediated intestinal inflammation during a T. spiralis infection in mice. PMID- 2592114 TI - In vitro generated mast cells investigated by monoclonal antibodies. AB - In the present study we have investigated the development of mast cells under in vitro conditions after depletion of mature mast cells of male Wistar rats by intraperitoneal application of distilled water. The studies were carried out both by monoclonal antibodies (MAb) against rat peritoneal mast cells and by cytochemical techniques. During cultivation the amount of MAb-positive cells increased from less than 5% to 64% after 3 weeks, which was accompanied by increased histamine levels and cell size. After 2 weeks the first Alcian blue stained mast cells were detectable, while safranin-positive granules appeared only after 3 weeks. These findings suggest that there are mast cell precursors in the peritoneum which may differentiate into mature mast cells. The antigen on the cell surface recognized by the MAb seems to be expressed during mast cell maturation. PMID- 2592115 TI - Immunoblot analysis of allergens in crude mosquito extracts. AB - Whole body extracts of Aedes albopictus (AAL), Aedes aegypti (AAE) and Culex quequectates (CQU) were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. At least 28, 37 and 26 polypeptides, molecular weights (MWs) ranging from 16 to 120 kilodaltons (kD), respectively, were visible following Commassie brilliant blue staining. Sera of two mosquito sensitive patients were examined for IgE binding to mosquito proteins by immunoblotting. Sera from both patients revealed IgE binding to 52- and 56-kD proteins of AAL. In addition, serum from patient B also bound 48 kD of AAL and did not bind any components of AAE and CQU. Serum from patient A also bound 32 and 58 kD of AAE, and bound only 58 kD of CQU. Sera from 2 control subjects, nonatopic and mosquito-negative atopic, did not bind specific human IgE to any proteins, as demonstrated by negative autoradiographs. Immunoblot analysis showed unique individual IgE-binding patterns and suggested that both genus- and species specific mosquito allergens exist. PMID- 2592116 TI - Inherited deficiencies of the late-acting complement components other than C9 found among healthy blood donors. AB - Among sera from 145,640 healthy blood donors in Osaka, 16 were found to have abnormalities in late-acting complement components other than C9. It was found that of these 16 sera, 2 were deficient in C5, 4 in C6, 6 in C7 and 4 in C8 alpha gamma-subunit. The incidence of deficiency of each component among the Osaka blood donors was calculated as follows: C5 deficiency, 0.0014%; C6 deficiency, 0.0027%; C7 deficiency, 0.0041%; C8 alpha-gamma-subunit deficiency, 0.0027%. We confirmed that 13 donors were healthy and 12 had no past history related to a complement component deficiency. From these results, not only C9 deficiency but also deficiencies of the other late-acting complement components were found among the healthy blood donors, but no early-acting component deficiencies were noted. PMID- 2592118 TI - Breast milk antibodies to foods in relation to maternal diet, maternal atopy and the development of atopic disease in the baby. AB - Breast milk samples were collected from 152 women during the first week after delivery. The levels of IgG and IgA antibodies to beta-lactoglobulin, ovalbumin and gliadin were assessed with an enzyme-linked immunosorbent assay (ELISA). The breast milk antibody levels did not differ significantly between mothers on a strictly cow's milk and egg-free diet, and mothers taking these foods. Moreover, the colostral food antibody levels did not differ significantly between atopic and non-atopic mothers. Neither was there any correlation between the colostral antibody levels and the development of atopic disease in the baby. I conclude that maternal antigen avoidance during late pregnancy does not affect the food antibody levels in colostrum. High levels of food antibodies in a colostrum sample seem not to offer protection against food allergy in the child. PMID- 2592117 TI - Adenosine potentiates neurally- and histamine-induced contraction of canine airway smooth muscle. AB - We studied the effect of adenosine on airway reactivity of isolated canine bronchial smooth muscle under isometric conditions in vitro. Administration of adenosine and its analogs increased the contractile responses of bronchial segments to electrical field stimulation in a dose-dependent fashion, where the rank order potency was N-ethylcarboxamideadenosine greater than adenosine greater than N-cyclohexyladenosine, but had no effect on those to exogenous acetylcholine. This potentiation was more pronounced at relatively low than at high stimulus frequencies, the maximal increase from the baseline responses being 56.3 +/- 9.6% at 1 Hz (mean +/- SE, p less than 0.01). Adenosine also increased the histamine-induced contraction causing a leftward shift of the histamine dose response curves, an effect that was abolished in the presence of atropine. These results suggest that adenosine potentiates airway responsiveness to vagal stimulation and to histamine through the activation of prejunctional A2 receptor, probably involving the accelerated release of acetylcholine from the cholinergic nerve terminals. PMID- 2592119 TI - Variability of allergenicity in eight strains of the green algal genus Chlorella. AB - Biochemical and immunological properties of allergen extracts from eight strains within four species of the unicellular green alga Chlorella were compared. The total protein and carbohydrate contents ranged from 13 to 29 and 18 to 47% of the dry weight, respectively. It was shown, both with RAST inhibition and immunoblotting, that Chlorella contain components which specifically bind to patient IgE antibodies. The relative allergen potency as assayed by RAST inhibition varied fivefold. Between seven and twenty IgE-binding components were identified in the various strains with molecular weights from 13 to 80 kD. Thus, the use of thoroughly characterized Chlorella strains is mandatory for preparation of relevant allergen extracts. PMID- 2592121 TI - Does computerized image analysis of sperm movement enhance the predictive value of semen analysis for in-vitro fertilization results? AB - The influence of semen quality on fertilization rates in an in-vitro fertilization (IVF) programme was studied by analysing both conventional semen parameters and computerized movement characteristics. The study was based on 407 inseminated oocytes which were obtained from 50 patients in 113 laparoscopies. Sperm concentration did not correlate strongly with the fertilization rate. Sperm motility and morphology were the most meaningful parameters in predicting fertilization success. A drop in fertilization rate was found when sperm motility or normal morphology were below 40%. Sperm velocity measured in semen was the only sperm movement parameter which correlated with the fertilization rate, albeit weakly. The latter was reduced when average sperm velocity in semen was less than 50 microns/sec. Conventional semen parameters seem to be more predictive of the fertilizing potential of an ejaculate than movement characteristics obtained by computerized image analysis. PMID- 2592120 TI - Granulomatous response in selective IgE-deficient SJA/9 mice infected with Schistosoma japonicum. AB - Granulomatous response was examined in selective IgE-deficient SJA/9 mice infected with Schistosoma japonicum. The average size of granulomas formed around newly deposited eggs in SJA/9 mice was significantly smaller than that in control C57BL/6 or SJL/J mice, although the numbers of adult worms recovered from each strain were comparable among them. Thus, IgE antibody specific to allergenic components of S. japonicum eggs seems to act as an amplifier for the formation of granulomatous lesions. PMID- 2592122 TI - Computer-assisted image analysis of sperm concentration in human semen before and after swim-up separation: comparison with assessment by haemocytometer. AB - Evaluation of male fertility is based predominantly on results from semen analysis and determination of the sperm concentration is one of the main parameters of the analysis. The availability of a fully automated videomicrographic digital image analyser would offer both an objective and rapid method for determination of the sperm concentration. In the present study the sperm concentration in 327 semen samples was determined by haemocytometer according to the World Health Organization guidelines, and also by a computer assisted digital image analyser system. Results were classified according to the routine procedure (haemocytometer) before statistical analyses. The computerized measurements caused a shift to the right in the frequency distribution of sperm concentration. Sperm concentrations were more often overestimated significantly (P less than 0.001) by the computerized measurements in semen samples with concentrations up to 80.0 x 10(6)/ml. This overestimation seemed to be caused by the presence of particles in seminal plasma that were recognized incorrectly as sperm by the computer program. The computerized digital image analyser gave an average sperm concentration of 2.2 +/- 0.6 x 10(6)/ml (mean +/- SEM) in 17 azoospermic semen samples while the routine procedure did not detect the presence of sperm cells. After removing the seminal plasma by washing and centrifugation with culture medium, and using the swim-up procedure to harvest motile sperm, the computerized measurements showed comparable results with the routine procedure for those sperm preparations (n = 44) with sperm concentrations greater than 5.0 x 10(6)/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592123 TI - Absence of correlation between the levels of ATP and other seminal compounds in semen and the results of human in-vitro fertilization. AB - As part of an in-vitro fertilization programme (IVF), semen levels of adenosine triphosphate, fructose, citrate, zinc, free L-carnitine and glycerophosphocholine were measured in 178 men. None of these substances appeared to have any predictive value with regard to the fertilizing potential of the semen during IVF. PMID- 2592124 TI - Quantitative evaluation of the maintenance and development of spermatocytes and round spermatids in cultured tubule fragments from immature rat testis. AB - Maintenance and development of spermatocytes and round spermatids was studied in an in-vitro incubation system. This system consisted of open tubule fragments from 26-day-old rat testes, obtained after collagenase treatment. The tubule fragments contained Sertoli cells and spermatogenic cells up to and including a small number of early round spermatids. The number of primary spermatocytes and round spermatids in the tubule fragments was estimated using flow-cytometric analysis, immediately after isolation and after 72 h of incubation. In addition, the activity of LDH-C4 in the tubule fragments was measured. After 72 h of incubation, the percentage of spermatocytes was reduced by 70-80%, but the percentage of spermatids was doubled. The total LDH-C4 activity per well was increased 2-3-fold during 72 h of incubation of the fragments. A modest improvement of the culture results was observed when a combination of FSH, insulin, retinol and testosterone was added to the medium. LDH-C4 activity was investigated to see whether it could be used as a quantitative marker of isolated and cultured spermatocytes and spermatids. It was observed that LDH-C4 activity per cell was decreased when spermatocytes and spermatids were isolated and/or incubated at 4 degrees C. However, the cellular enzyme activity returned to control values during subsequent incubation of the cells at 32 degrees C, either in the absence or presence of a protein synthesis inhibitor. Cellular LDH-C4 activity may be influenced not only by temperature, but possibly also by other cell isolation conditions. It is concluded that LDH-C4 activity may not be a reliable quantitative marker for the presence of spermatocytes and spermatids in culture, but should be used in combination with other analytical methods such as DNA estimation and DNA flow cytometry. PMID- 2592125 TI - Bias to routine semen analysis by uncontrolled changes in laboratory environment- detection by long-term sampling of monthly means for quality control. AB - To detect systematic bias in the results of routine semen analysis over time, monthly means of semen parameters determined by the recommended WHO methods were computed. The analysis was based on a total sample size of 1784 ejaculates and included 18 months of observation. In addition to slight changes of morphology estimates caused by a change of laboratory staff, a major bias in the measurement of sperm motility could be detected. This observation triggered a search for changes in protocols not previously given the required attention. It revealed that the newly introduced use of polypropylene syringes with a mounted needle for accurate measurement of seminal volume impaired sperm motility. More detailed investigation by computerized sperm motion analysis in 10 semen samples treated simultaneously in different ways revealed that predominantly it was the needle which caused the drop in proportion of motile sperm (glass cylinder: 50.3 +/- 4.1% vs. syringe + needle: 26.6 +/- 5.3%; mean +/- SEM) and not the contact with the plastic material alone (syringe alone: 43.4 +/- 4.8%). Other motion parameters such as curvilinear velocity (36.0 +/- 1.6 microns/sec), linearity (78.5 +/- 8.4%) and lateral head displacement (3.8 +/- 0.9) were not influenced by the different methods of handling. The results indicate that long-term sampling of monthly means may serve as part of a quality control scheme in semen analysis. PMID- 2592126 TI - Fluid-phase transcytosis in the primate epididymis in vitro and in vivo. AB - Ligated tubules from the corpus epididymidis of men and monkeys were incubated in medium containing horseradish peroxidase (HRP) as a marker for fluid-phase endocytosis. HRP was localized by light and electron microscopy after 0, 15, 30 and 60 min of incubation. Movement between the cells was prevented by tight junctions, but bypass of this barrier was apparently achieved by an intracellular vesicular mechanism leading to a time-dependent appearance of HRP in the lumen. Uptake of HRP into basal cells and capture by the lysosomal apparatus of principal cells were also observed. HRP-filled vesicles also appeared in the basal, mid and apical cytoplasm of epithelial cells in the caput 1 h after injection of the tracer into the epididymal circulation of the monkey, suggesting that this pathway also operates in vivo. PMID- 2592127 TI - Anesthesia for the dermatologic surgeon. PMID- 2592128 TI - Misconceptions about antimalarials. PMID- 2592130 TI - Scleromyxedema associated with non-Hodgkin lymphoma. PMID- 2592129 TI - Scleromyxedema. PMID- 2592131 TI - Buerger's disease. PMID- 2592132 TI - How to write and take objective, multiple choice examinations. Quantitative analysis of the scientific data base. AB - Although there are numerous ways in which physicians evaluate one another and themselves, the multiple choice examination has become the key method for evaluating the scientific data base of both medical students and postgraduate physicians. Knowledge of the mechanisms at work in such examinations is thus important for both giving and taking these examinations. Analysis of these mechanisms is now provided. PMID- 2592133 TI - Intralesional injection of tetracosactid in the treatment of localized vitiligo. PMID- 2592134 TI - Linear basal cell epithelioma. PMID- 2592135 TI - Morphea-like basal cell epithelioma. PMID- 2592136 TI - The effects of DNCB therapy on the T-cell subsets of the cases with alopecia areata. PMID- 2592137 TI - Induction of resistance in Oncomelania hupensis nosophora against Schistosoma japonicum, but not against Paragonimus ohirai, using irradiated miracidia. AB - Oncomelania hupensis nosophora snails sensitized with X-irradiated Schistosoma japonicum miracidia demonstrated resistance against a following challenge infection with non-irradiated homologous miracidia. The resistance in O. h. nosophora against S. japonicum was acquired within 1 day of sensitization, and it was strongest in a group challenged at an interval of 3 days. The resistance persisted for at least 4 weeks. Histological examinations revealed amoebocyte accumulation around the challenged S. japonicum sporocysts. On the other hand, when O. h. nosophora sensitized by exposure to X-irradiated P. ohirai or S. japonicum miracidia were subsequently challenged with normal P. ohirai miracidia, no resistance was observed, although they expressed the resistance against heterologous S. japonicum infection. PMID- 2592138 TI - Cross-immunity between Haemonchus contortus and Trichostrongylus colubriformis in sheep. AB - Cross-protective immunity between the nematode parasites, Haemonchus contortus and Trichostrongylus colubriformis, was examined in sheep vaccinated with irradiated larvae of either species. Secondary immunological responsiveness stimulated in this manner protected only against challenge infection with the species used for vaccination. Significant cross-protective immunity was not observed. Titres of serum antibody to an extract of adult but not infective larval T. colubriformis reflected the specificity for protective immunity. Immediate hypersensitivity skin reactions to nematode extracts did not reflect the antigen-specificity for protective immunity. PMID- 2592139 TI - Acanthocheilonema viteae (Dipetalonema viteae) in mice: attempts to correct the low responder phenotype of the BALB/c host. AB - Attempts were made to correct the low responder phenotype of microfilaraemic Acanthocheilonema viteae (Dipetalonema viteae) infected BALB/c mice through the transfer of immune spleen cells and immune serum from amicrofilaraemic B10 background mice. The transfer of immune cells and serum prior to infection failed to influence development of microfilaraemia in BALB/c recipients. Attempts to alter the course of an established microfilaraemia in BALB/c mice through the transfer of 3 x 10(7) immune spleen cells were unsuccessful but transfer of 3 x 10(8) cells reduced microfilaraemia temporarily. Treating microfilaraemic BALB/c mice with immune serum brought about a rapid reduction in microfilaraemia. This effect was only temporary and numbers of circulating microfilariae returned to control levels within a short time. Repeated serum transfers reduced the microfilaraemia only during the period of treatment. Similar results were obtained when immune serum was given to microfilaraemic, immunodeficient CBA/N mice. PMID- 2592140 TI - The effect of infusions of microfilariae (L1 larvae) of Dirofilaria immitis in dogs. AB - Four pups were given three intravenous infusions of microfilariae over a 7-month period to determine if radiographic changes could be detected in the lungs while sensitivity to first stage microfilariae was being induced. Mild pathological changes occurred but these could not be detected on any of the radiographs. Radiographic changes described by others and 'Eosinophilic lungs' did not result from the immune response to the first stage larvae. PMID- 2592141 TI - Membrane carbohydrate characterization of Acanthamoeba astronyxis, A. castellanii and Naegleria fowleri by fluorescein-conjugated lectins. AB - A comparative study of membrane carbohydrate characteristics of pathogenic and non-pathogenic trophozoites and cysts of free-living Acanthamoeba castellanii, Naegleria fowleri and A. astronyxis, respectively from sewage sludge in India was carried out by means of fluorescein-conjugated lectin binding using eight lectins. Two lectins, viz. Concanavalin A and Phytohaemagglutinin P, could bind all free-living amoebae at different concentrations. The most notable feature of the study is that peanut agglutinin (PNA) and wheatgerm agglutinin (WGA) can differentiate between the pathogenic A. castellanii and non-pathogenic A. astronyxis strain, respectively. However, Ulex agglutinin I (UEA I) was the only lectin positive to both pathogenic A. castellanii and N. fowleri. During in vitro conversion from trophozoites to cysts, A. castellanii and N. fowleri cysts gained WGA-specific saccharide whereas A. castellanii; A. astronyxis and N. fowleri lost or reduced Dolichos biflorus agglutinin, PNA; WGA and ConA, and UEA I-specific saccharides, respectively. Neuraminidase could not alter the fluorescein-lectin binding to WGA and PNA. These demonstrated that only two lectins can recognize the factors giving Acanthamoeba their pathogenic (PNA-specific) and non pathogenic (WGA-specific) status. More interestingly, UEA I can only differentiate between pathogenic and non-pathogenic amoebae. It is also suggested that during stage conversion the surface of the organism exhibited replacement of saccharides. PMID- 2592143 TI - Intraovular development and moulting of Toxocara pteropodis. AB - Observations of Toxocara pteropodis eggs removed from an adult worm and embryonated in 0.05 M-sulphuric acid showed the first moult to occur on the sixth day followed by the second moult over days 8-11, as indicated by the finding of a transient, loose, double-layered sheath over the definitive cuticle. Infectivity to mice first developed on day 11, reached a maximum at 36 days and then waned over the next 6 months. Details of larval development are described and the significance of loose sheaths on larvae recovered from tissues is discussed. PMID- 2592142 TI - Cu-Zn-superoxide dismutase activity in Moniezia expansa: inhibition by pyrimidine derivatives. AB - Copper-zinc, cyanide-sensitive superoxide dismutase (Cu-Zn-SOD) was detected in homogenates of Moniezia expansa. The enzyme was purified by a sequence of multiple differential centrifugations, ammonium sulphate precipitation, ion exchange and G-75 Sephadex column chromatography. The final enzyme preparation had a specific activity of 623.00 +/- 9.97U per mg protein and, after isolation, a single-staining band on acrylamide-SDS gels was detected which coincided with enzyme activity. The inhibitory activities of several benzimidazoles and several novel pyrimidine derivatives were determined on purified extracts of the M. expansa Cu-Zn-SOD. The results indicated that the percentage inhibition of Cu-Zn SOD by some pyrimidine derivatives (6-amino-1, 3-dimethyl-5-nitroso-uracil, 6 amino-5-methyl-5-nitroso-uracil and 5-amino-uracil) was markedly higher than inhibition with the benzimidazoles. PMID- 2592144 TI - The acquirement of growth ability for third-stage larvae of Strongyloides ratti during the head-passage in the rat. AB - The role of larval passage through the head in the course of the migration of Strongyloides ratti in rats was investigated. Third-stage larvae (L3) recovered from various portions of donor rats were re-injected into the skin, cranial cavity and small intestine of recipient rats to check their ability for further growth. Cultured L3 (L3c) and the L3 recovered from the skin of donor rats (L3s) did not survive in the small intestine after intestinal inoculation. However, intestinal inoculation of L3 recovered from the head of donor rats (L3h) revealed growth to the adult stage. Cultured L3 injected into the cranial cavity of rats also became adult worms in the small intestine. L3 incubated in the cranial cavity for more than 24 h could grow in the small intestine of the recipient rats. These experiments suggest that S. ratti L3 acquire their ability to mature in the small intestine during their migration through the head of rats. PMID- 2592145 TI - Endocytosis in cultures of Blastocystis hominis. AB - A study of the function of the electron-dense pits in the vacuolar and granular forms of Blastocystis hominis was undertaken. Immuno-electron microscopy using anti-clathrin antibody and colloidal gold demonstrated clathrin to be associated with all forms of the pits and some cytoplasmic vesicles. Cationized ferritin traced the pathway of endocytosis from the surface of the coated pits through internalization via electron-dense coated vesicles and uncoated vesicles and tubules in the cytoplasm. The cationized ferritin particles accumulated in the central vacuole, suggesting a metabolic or storage role for this structure. Differences in the accumulation of cationized ferritin particles were noted between vacuolar and granular forms. The hydrolytic enzyme acid phosphatase was not detected within the central vacuole suggesting that this structure does not act as a lysosome. PMID- 2592146 TI - Characterization of the major immunogen in the excretory-secretory products of exsheathed third-stage larvae of Trichostrongylus colubriformis. AB - The excretory-secretory products of exsheathed third-stage larvae of Trichostrongylus colubriformis conferred some protection to guinea pigs against homologous challenge. A glycoprotein with an apparent molecular mass of approximately 94 kDa was the dominant immunogen in post-exsheathment products. Immunoblots revealed IgG antibodies to this glycoprotein in sera from multiply infected guinea pigs and some sheep, and in sera of guinea pigs after three truncated infections which had been restricted by anthelmintic treatments to development of the third parasitic stage. IgA antibodies to this protein were also found in intestinal lymph of a naturally infected sheep. Fluorescent antibody studies indicated that this 94 kDa component was associated with cells in the central body cavity of third-stage larvae, but was absent from fourth stage larvae or adult worms. Fractionation and protection assays in guinea pigs revealed that while the native and aggregated 94 kDa protein conferred some host protection, it was not the only protective component of the excretory-secretory products of exsheathed third-stage larvae of T. colubriformis. PMID- 2592147 TI - Clinical survey of Entamoeba gingivalis by multiple sampling in patients with advanced periodontal disease. AB - A clinical survey of Entamoeba gingivalis was conducted in patients with advanced periodontal disease. A total of 100 specimens were taken from 10 patients (four females and six males) who were each sampled at 10 disto-facial random sites. The oral hygiene of the persons scored from good to fair to poor and very poor. The age of the test persons ranged from 20 to 68 years. All persons examined harbored E. gingivalis: the minimum prevalence was four sites positive out of 10 and the maximum prevalence was 10 sites positive out of 10 for the protozoan. It is recommended that for reliable testing of the presence of E. gingivalis at least five-10 different sites should be examined within the periodontium of each patient. Data reported earlier in the literature on the incidence of E. gingivalis--obtained after a single sampling per individual--are believed to be on average too low and, therefore, should be interpreted with caution. PMID- 2592149 TI - Decrease of acid phosphatase activity in murine peritoneal macrophages infected with Leishmania donovani. AB - The effect of infection with Leishmania donovani on the activity and isoenzyme composition of acid phosphatase within individual murine peritoneal macrophages maintained in vitro was studied. Concentrations of acid phosphatase activity and number of intracellular parasites were quantitated using a computer-assisted cytospectrophotometry system. Changes in the isoenzyme composition of macrophages during infection with L. donovani were detected by comparing the patterns of acid phosphatase levels between macrophages treated in the absence and presence of an enzyme inhibitor. It was observed that the concentration levels of acid phosphatase activity in macrophages were decreased significantly by infection with L. donovani. An inverse relation existed between concentration of acid phosphatase activity and the number of intracellular L. donovani. Reduced concentrations of acid phosphatase activity were also observed in macrophages uninfected but exposed to L. donovani. The isoenzyme composition in macrophages did not change during the course of infection with L. donovani. These results demonstrate that L. donovani reduces the acid phosphatase activity of macrophages. PMID- 2592148 TI - Experimental infection of Indonesia Taenia (Samosir strain) in domestic animals. AB - Three 58-day old Small-Ear-Miniature (SEM) pigs, six 36-day old Landrace-Small Ear-Miniature (L-SEM) pigs, and two 5-day old Holstein calves were each fed 3000 or 30,000 Indonesia Taenia (Samosir strain) eggs and sacrificed 27-195 days after inoculation. A total of 4922 cysticerci were recovered only from the livers of the three SEM pigs (1977 cysticerci) and six L-SEM pigs (2945 cysticerci). The infection rate in pigs was 100%. Cysticerci recovery rates of SEM and L-SEM pigs were 22.0% and 1.6%, respectively. Calves were not susceptible to Indonesia Taenia. More cysticerci were found in the liver parenchyma (L-SEM, 66.4%; SEM, 76.2%) than on the liver surface (L-SEM, 33.6%; SEM, 23.8%) of the infected animals. Most (99.86%) of the cysticerci recovered from the livers of L-SEM pigs were degenerated or calcified but 77.9% of those in the livers of SEM pigs were mature and only 22.1% were degenerated or calcified. Measurements of length, width, diameters of protoscolex, rostellum, and sucker and hooklet pattern indicated that Indonesia Taenia is very similar to Taiwan Taenia and very different from Taenia saginata and Taenia solium. The present findings indicate that Indonesia Taenia and Taiwan Taenia may be the same new species. PMID- 2592150 TI - Knocked-out teeth can be saved. PMID- 2592153 TI - Oculoplastic surgery. PMID- 2592151 TI - Tooth movements associated with deep overbite correction in Class II division 1 malocclusions. AB - The orthodontic profession has assumed much of the responsibility for the improvement in function of the teeth and jaws. Since function is closely associated with overbite, the correction of vertical overbite discrepancies comprises a major part of clinical orthodontics. This investigation was undertaken to describe the movements that teeth undergo during the correction of excessive overbites and to correlate these movements to the change in overbite. A total of 87 cases were selected from the records of the Indiana University School of Dentistry, Department of Orthodontics. The selected cases had an excessive pre treatment overbite of 4.0 mm or more as seen cephalometrically and a satisfactory post-treatment result. In addition, they were clinically determined to be post pubertal, indicating essentially no growth potential during the treatment period. Pre and post-treatment tracings of the cephalograms were made and measurements collected from the tracings. Superimpositions were prepared of the pre and post treatment radiographs and the general trends that appeared were noted. The change in overbite was correlated to tooth movements of the Class II Division 1 correction using the Pearson test of correlation coefficients. The results indicate that the tooth movements most commonly seen in treatment to reduce excessive overbite occur mainly in the mandibular arch. In Class II Division 1 cases, the change was significantly correlated to the reduction in vertical height of the mandibular incisor and to the increase in the angulation of the mandibular incisor to the mandibular plane. Not all measurements recorded were significantly correlated to the change in overbite.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592154 TI - A new classification of blepharoptosis. PMID- 2592152 TI - Cephalometric changes in Angle Class II treatment. AB - The efficiency of Angle class II correction using functional orthopedic appliances is well accepted in the literature. However, there are controversial views as to whether dentoalveolar processes, growth alteration or jaw displacement predominates. This study was therefore designed to clarify the mode of action in class II treatment using Bimler's "GebiBformer". Cephalometric radiographs taken in 146 patients before and after treatment were analysed (mean age at beginning of treatment: 9.2 years). In these patients, Angle class II of one premolar width was successfully corrected during a mean 4.2 years of treatment. Matching data of 100 patients, who had undergone functional jaw orthopaedics because of class I malocclusion served as comparison group. According to cranio-facial growth type, the patients were subdivided in to three subgroups. Statistical analyses were performed using the t-test. The results indicate, that point A develops posteriorly relative to the nasion in the class II group and anteriorly in the class I group. The length of the maxilla develops equally in the groups compared. The sagittal discrepancy between upper and lower jaw deminishes significantly in treated class II patients. The B point comes only slightly more anteriorly in the class II group than in the control group. Shape and length of the mandible showes similar development in the two groups. In correcting class II with the "GebiBformer", changes in the craniofacial pattern take place. However, class II correction cannot be attributable to skeletal changes alone. It can only be explained by additional dentoalveolar changes. PMID- 2592155 TI - Ptosis revision. PMID- 2592156 TI - Surgical treatment of thyroid-related eyelid retraction. PMID- 2592157 TI - Twelve years' experience with the Mohs-Tromovitch technique of skin cancer removal. PMID- 2592158 TI - Association of uveal melanocyte destruction in melanoma-bearing swine with large granular lymphocyte cells. AB - Sinclair strain miniature swine spontaneously develop and regress malignant melanoma lesions, with uveitis and vitiligo occurring subsequent to tumor regression. Peripheral blood lymphocytes (PBL) of Sinclair swine undergoing tumor regression and melanocyte destruction demonstrated significant lytic activity against K562, porcine semiallogeneic uveal melanocytes, and melanoma cells in 4-h chromium release assays. The ability of porcine PBL to lyse these target cells appears to be an age-associated immune response, as evidenced by the relative inability of PBL of pigs less than 4 weeks old to lyse target cells. In young adult pigs, however, PBL cytotoxic activity significantly increases; piglets 6 weeks old and older demonstrate efficient killing of all three targets. Conjugate formation assays demonstrate that a lymphoid effector cell possessing large granular lymphocyte (LGL) morphology may be involved in melanocyte destruction. These findings suggest that a LGL subpopulation may participate in melanoma and melanocyte destruction which can induce a uveitic syndrome in Sinclair swine with melanoma. PMID- 2592159 TI - Actin filament polarity at the site of rod outer segment disk morphogenesis. AB - The rod outer segment (ROS) is attached to the visual cell body by a connecting cilium. Axonemal components of this cilium extend into the ROS, an organelle which undergoes continuous renewal throughout life. New membranous disks are added at the ROS base, while older ones are shed from the tip. The formation of new disks is believed to result from plasma membrane evaginations at the distal end of the connecting cilium, but the mechanism responsible for disk morphogenesis is not yet understood. Within the ciliary axoneme, at the base of the ROS, an actin-rich domain has been localized with immunoelectron microscopy, and filamentous actin has been detected with fluorescent phallotoxin. However, actin filaments have not previously been observed in electron micrographs of this region. We now report that a meshwork of decorated actin filaments was observed within the center of the ciliary axoneme, at the base of the ROS, after visual cells were permeabilized with saponin and incubated with myosin subfragment-1 (S 1). Furthermore, individual filaments were seen to extend from the center of the axoneme into the base of the ROS disk stack by passing between pairs of ciliary microtubule doublets. Arrowheads on these filaments uniformly pointed toward the cilium, while the barbed (or fast-growing) ends were oriented in the direction of disk expansion and were often associated with the ROS plasma membrane. In control retinas, undecorated filaments were observed. Thus, S-1 binding did not induce filament formation. These results suggest that an actin filament network may provide cytoskeletal support and guidance for the growing ROS disks. PMID- 2592160 TI - Protein-related abnormalities in keratoconus. AB - Two-dimensional electrophoretic maps of extracts from eleven normal and eleven keratoconus corneas were compared. Of the eleven corneas analyzed, eight were pooled and the remaining three were analyzed individually. Several differences were demonstrated between electrophoretic patterns of normal and keratoconus corneas. In keratoconus corneas, 1) two abnormal components (MW 54kD and 26kD) were observed; 2) three normal corneal components (MW 12kD, 14kD, and 39kD) were present in significantly higher amounts; and 3) three normal corneal proteins (MW 66kD, 55kD, and 13kD) were present in reduced amounts. The molecular weight and isoelectric point of one of the normal corneal proteins that we found to be reduced in keratoconus corneas were close to that of a subunit of prolyl-4 hydroxylase, an enzyme required for hydroxylation of proline residues of collagen. The possibility the abnormal proteins detected in the keratoconus corneas were derived from those normal corneal proteins which were absent or were present in reduced amounts in the keratoconus corneas remains to be established. This study may provide protein markers for elucidation of the biochemical abnormality in keratoconus. PMID- 2592161 TI - Time-lapse videomicroscopic study of in vitro wound closure in rabbit corneal cells. AB - This study used video time-lapse recording to characterize the dynamic features of corneal epithelial cells and keratocytes during in vitro wound closure. Confluent cultures of these two cell types from rabbits were established in Rose chambers. A wound 4 or 10 mm in diameter was produced in the center of each culture by mechanical removal of cells. Wound closure was recorded by videomicroscopy for 2-3 days and reviewed at a playback speed of 400 times normal. The epithelial cells at the wound margin initiated migration by extending lamellipodia with undulatory motions. Successive tiers of cells moved as a continuous sheet in a unified and coordinated manner while maintaining intercellular linkage. The migration was unidirectional, toward the wound center. The mean migration rate of the leading cells was 104 microns/hr. The trailing cells migrated at successively slower rates, inversely proportional to their distance from the wound margin. Mitosis was rare during migration but did occur simultaneously. The mitotic rate was 3.7 mitoses/100 cells. The relative mitotic frequency was 0.23 mitosis/hr. By contrast, in keratocyte cultures, the cells around the wound margin migrated individually and asynchronously without intercellular connection. Initially the cells moved generally toward the wound space, but later, different cells migrated in different directions. The mean migration rate was 15 microns/hr. Mitosis occurred frequently. The mitotic rate was 25.3 mitoses/100 cells, and the relative mitotic frequency was 1.33 mitoses/hr. The cell cycle duration was 9.9 hr. Thus corneal epithelial cells and keratocytes showed fundamentally different characteristics and mechanisms of wound closure in vitro. PMID- 2592162 TI - Kinetics of phagocytosis in trabecular meshwork cells. Flow cytometry and morphometry. AB - Confluent human trabecular meshwork (HTM) cells from three different donors and at various stages of serial passage were fed fluorescein-labeled polystyrene beads. Phagocytosis was monitored for up to 6 days using flow cytometry, fluorescence microscopy, and morphometric calculations from comprehensive electron microscopic observations at key time points. During the first 4 hr after initiation of phagocytosis, the confluent endothelial monolayer lost its cohesiveness and became segregated into separate cells. During the first 3 days the cells underwent marked and progressive changes in shape and size. After 4 days, some cells detached from the dish, as necrotic debris and degenerative changes appeared. The kinetics of phagocytosis in this stable, confluent monolayer showed that recruitment (the percentage of cells which had ingested at least one bead) proceeded semilogarithmically, with 50% of the cells recruited by 8 hr and 97% by 96 hr. The time course of phagocytosis (ie, the average number of beads phagocytosed per cell) is described by a sigmoidlike curve, reaching half maximum at 40 hr and maximum (about 500 beads per cell) at 96 hr. The rate of uptake (ie, the first derivative of the average number of beads per cell) reached a peak (nine beads per cell per hr) at 24 hr and then decelerated slowly over the next 5 days. Cytochalasin B treatment, as a control, reduced phagocytosis by approximately 70%. Flow cytometry, when combined with electron microscopy, should provide a useful tool to examine phagocytosis in HTM cells exposed to steroids and other hormones and drugs. PMID- 2592163 TI - Ocular torsion measured by TV- and scanning laser ophthalmoscopy during horizontal pursuit in humans and monkeys. AB - Ocular torsion during horizontal foveal pursuit and fixation was measured in five human subjects and two trained monkeys (Macaca fascicularis) by direct analysis of the ocular fundus rotation. In the monkeys the fundus images of either eye were generated with a TV-ophthalmoscope while the contralateral eye pursued an 8' visual target moving sinusoidally (0.3-0.9 Hz, +/- 5 degrees) in the horizontal plane. In the humans a scanning laser ophthalmoscope (SLO) generated the fundus image of the ipsilateral eye, which pursued the visual target (same parameters as in the monkeys) mixed electronically into the laser scan raster. The image sequences were stored on videotape and subjected to a frame-by-frame rotation analysis. In both the humans and the monkeys, torsion (fundus rotation about the visual axis) sinusoidally modulated (up to 8 degrees peak-to-peak) during foveal pursuit, approximately in phase with horizontal eye position. Intorsion (nasal movement of the upper eye pole) or extorsion was found during pursuit in the temporal or nasal direction. Torsion showed considerable intra-individual fluctuation and interindividual variability with regard to phase and modulation depth relative to the pursuit movements, and was interspersed with irregularly occurring rapid deflections. Torsion of the conjugate, nonpursing eye was similar to torsion of the pursuing eye. In contrast, torsion during fixation was only loosely correlated with horizontal eye position. Slow torsional drifts and large, rapid deflections (up to 6 degrees) occurred in either direction at a given fixation point in the horizontal plane. We conclude that ocular torsion during horizontal pursuit in primates is actively generated by a separate, neural oculomotor subsystem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592164 TI - Effect of saccade size on presaccadic spike potential amplitude. AB - Presaccadic spike potentials were recorded from electrodes placed at the inner canthus and below the eye in ten normal subjects. The responses to twenty abducting and twenty adducting saccades were back-averaged from the beginning of the eye movement, and separate waveforms were obtained for saccades of 20 degrees, 10 degrees, 7.5 degrees, 5.0 degrees, and 2.5 degrees. The spike onset and peak latencies relative to the beginning of the eye movement and the onset peak amplitudes were measured. Throughout the range of saccade sizes, the onset and peak occurred earlier with adduction than with abduction, but there was no consistent change in the latency values with saccade size. The amplitude, however, showed an increase with saccade size up to movements of 10 degrees, although statistical analysis showed that these amplitude changes were not consistently significant. Comparison of the 20 degrees saccades to the 10 degrees saccades and the 10 degrees saccades to the 7.5 degrees saccades revealed no statistically significant differences in amplitudes. The difference between the 7.5 degrees and the 5 degrees saccades, however, was statistically significant (P less than 0.05) but only at the inner electrode with abduction; comparison of the 5 degrees and 2.5 degrees results showed a significant difference (P less than 0.01) at the inner electrode with both abduction and adduction. Comparison of the 7.5 degrees and the 2.5 degrees showed a significant difference (P less than 0.01) at both electrode sites with abduction and adduction. These findings are discussed with respect to the previously suggested origin of the spike potential and the choice of the recording electrode site. PMID- 2592165 TI - Adenosine: autoradiographic localization and electrophysiologic effects in the cat retina. AB - Autoradiography with 3H-adenosine was used to localize cells that accumulate adenosine in the cat retina. Electrophysiologic effects elicited by adenosine on DC-electroretinograms (ERG) and optic nerve responses (ONR) were studied in isolated, arterially perfused cat eyes. Subpopulations of cells localized in the ganglion cell layer and inner nuclear layer showed clear labeling for adenosine. This purine nucleoside enhanced the ERG b-wave and the standing potential; depressed the light peak; and markedly depressed the ONR, in which it reduced the amplitudes of the ON-, plateau-, and OFF-components. A vasodilatory action of adenosine was documented by an increase in perfusion flow rate. Our data suggest that adenosine in cat retina has complex modulatory effects, involving the retinal pigment epithelium, neuronal structures, blood vessels, and probably glial cells. PMID- 2592166 TI - First International Ioversol Symposium: A Clinical Summary. Scottsdale, Arizona, February 23-25, 1989. PMID- 2592167 TI - Hemodynamic effects of ioversol in the dog and rat. AB - The hemodynamic effects of selectively administered ioversol were examined in the dog and rat. At concentrations ranging from 32% to 37% I, wt/vol, ioversol was compared with nonionic (iohexol, iopamidol) and ionic (diatrizoate) contrast media for cardiovascular responses following injections into the femoral vein, right and left coronary arteries, left ventricle, and the pulmonary and femoral arteries of the dog, and into the carotid artery of the rat. Regardless of the intravascular route of injection, ioversol generally caused minimal effects on the heart rate, minimal to moderate decreases in myocardial contractility, left ventricular pressure, mean arterial pressure, pulmonary vascular resistance, and systemic vascular resistance. These effects of ioversol were comparable to those of iohexol and iopamidol, and were relatively less profound than those of diatrizoate. Under experimental conditions injections of ioversol exerted hemodynamic effects comparable to those of other nonionic agents, yet relatively diminished as compared with a representative high-osmolality ionic contrast agent. These results suggest that the nonionic contrast agent, ioversol, should be well tolerated in patients following injections via similar intravascular routes. PMID- 2592168 TI - Reproductive, developmental, and genetic toxicology of ioversol. AB - The authors examined the reproductive, developmental, and genetic toxicity of ioversol in several in vivo and in vitro systems. In Segments I, II, and III reproductive toxicity studies, ioversol did not produce teratogenic effects in either rats or rabbits at daily intravenous dose levels of up to 3.2 g I/kg/day. Daily intravenous injections in male and female rats did not adversely affect fertility or reproductive function. Offspring derived from dams treated with ioversol also developed and reproduced in a normal fashion. Four genetic toxicity studies employing bacterial and mammalian assay systems, and using both in vitro and in vivo methods, indicated that ioversol did not possess mutagenic or clastogenic activity. PMID- 2592169 TI - Acute and subacute toxicity studies of ioversol in experimental animals. AB - The authors examined the acute and subacute toxicity of the low-osmolality nonionic radiographic contrast agent, ioversol. The median lethal dose (LD50) of ioversol administered intravenously to mice, rats, rabbits, and dogs was more than 12 g I/kg, which exceeds the maximal anticipated clinical dose by at least tenfold. When the acute intravenous toxicity of 35% I, wt/vol, ioversol was compared with 35% I, wt/vol, iohexol and 37% I, wt/vol, iopamidol in mice, no significant differences in LD50 values or general toxicity were found. Ioversol also was administered via intrathecal routes to rats, dogs, and monkeys. In a comparative study, acute intracisternal injections of 35% I, wt/vol, ioversol in rats demonstrated far less toxicity than 35% I, wt/vol, iohexol and 37% I, wt/vol, iopamidol, a result that may be due to the increased hydrophilic tendency of ioversol relative to iohexol and iopamidol. Acute intracisternal injections of 43% I, wt/vol, ioversol, 35% I, wt/vol, iohexol, and 37% I, wt/vol, iopamidol into dogs at 160 or 240 mg I/kg, demonstrated comparable, but only minimal, toxicity. Monkeys given lumbar intrathecal injections of ioversol tolerated 60 mg I/kg well with no resulting arachnoiditis. Subacute toxicity studies involving 4 week daily intravenous injections (0.2, 0.8, and 3.2 g I/kg/day) in rats and dogs showed ioversol to be well tolerated. The signs of toxicity included a reversible renal cytoplasmic tubular vacuolation in the rat at high doses and a reversible hepatocyte vacuolation in the dog at the same high dose. However, clinical chemistry tests showed no signs of renal or hepatic dysfunction, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592170 TI - Biodistribution and excretion of 125I ioversol in conscious dogs. AB - Radiolabeled ioversol was injected intravenously into two male and two female beagle dogs (6.7 to 10.4 kg) at two dose levels each (0.2 and 1.0 g I/kg). Blood levels of radioactivity were monitored at 2, 5, 10, 20, 40, 60, 90, and 120 minutes and at one and two days. Urine and feces were collected in metabolism cages for two days, at the end of which the dogs were killed and organs or tissues (kidneys, liver, spleen, lungs, thyroid glands, heart, gonads, and muscle) were sampled. Radioactivity in tissues and excreta was assayed. Biexponential disappearance of radioactivity from blood was observed in three of four dogs at each dose level. Distribution half-lives averaged 2.5 to 3.5 minutes. Elimination half-lives averaged 51 to 54 minutes. Volumes of distribution averaged 25% to 27% of body weight. No organ retention was evident at 48 hours. Recovery of ioversol in urine and feces averaged 86% to 88% of the administered dose, of which all but a few percent was recovered in urine. On chromatographic assay, ioversol accounted for an average of 103% to 109% of radioiodine, suggesting, within the experimental limits of the assay, that ioversol is excreted unchanged. No dose-related differences were evident in any of these measures. The pharmacokinetics and biodistribution of ioversol are consistent with those of other extracellularly distributed iodinated contrast agents that are excreted by the kidney. PMID- 2592171 TI - Psyllium in metamucil lowers cholesterol levels. PMID- 2592172 TI - Behavioral risk factor surveillance system. PMID- 2592173 TI - Artificial intelligence: expert systems. PMID- 2592174 TI - Left ventricular thrombectomy in the early postinfarction period. PMID- 2592175 TI - Methane production in patients with colorectal carcinoma. AB - In searching for a screening test to identify a population at high risk for large bowel cancer, methane production was measured in 45 patients with colorectal carcinoma compared with 67 individuals who served as a control group. There was no significant difference in methane production between the colorectal cancer patients and the control group (37.8 and 25.4% respectively). Within the colorectal cancer group 54% of the males were methane producers compared with 19% of the females (P = 0.03). There were no differences according to disease stage. In view of these results, we see little value in using expired air methane concentration as a screening test for large bowel cancer. PMID- 2592176 TI - Long-term survival of patients with chronic obstructive pulmonary disease following mechanical ventilation. AB - Fifty patients with chronic obstructive pulmonary disease (COPD) who survived their first artificial ventilation were followed for 15 years. Five-year survival was 30%, median survival 23.5 months, and average survival 44.9 months. Sudden death occurred in 47% of the patients (40% at home and 7% in the hospital). Using multivariate analysis, survival correlated positively and significantly with partial pressure of arterial oxygen (PaO2) on discharge (P less than 0.02), presence of wheezes or rhonchi (P less than 0.02), absence of right heart failure on admission (P less than 0.02), and male sex (P less than 0.05), and negatively with age (P less than 0.03). Sixty percent of the patients were artificially ventilated at least twice. Prognosis was better as the number of ventilations increased after the first ventilation. Our finding that discharge PaO2 was the factor that correlated best with survival suggests that treatment for these patients consist of continuous long-term use of domiciliary oxygen. PMID- 2592177 TI - Sudden death in young Israeli soldiers. Analysis of 83 cases. AB - During the years 1974-86 in the Israel Defense Force (IDF), 83 soldiers aged 17 39 years died suddenly and unexpectedly. Cardiac causes accounted for 56% of the deaths, neurological causes for 19%, other diseases for 8% and in 17% the cause of death was unknown. Causes of death varied between soldiers younger and those older than 30 years of age. Ischemic heart disease accounted for 58% of deaths in soldiers greater than 30 years old but was an infrequent cause of death in subjects less than 30 years (4%). Congenital cardiac anomalies (27%) and myocarditis (15%) accounted for most deaths in subjects less than 30 years of age. Epilepsy was a common cause of sudden death (10%), occurring mainly during sleep, and was related to poor medical control. Effort-related deaths occurred in 25 cases (30%) and were mainly associated with cardiac causes. Syncope (18%) and chest pain (18%) were common symptoms prior to death. According to our data and previous reports, sudden death continues to be an unresolved medical problem in young adults. Preventive measures should include a more thorough evaluation of symptoms such as syncope and chest pain, particularly when occurring during or after exercise. Furthermore, early coronary artery disease should not be disregarded in subjects as young as 30 years of age. PMID- 2592178 TI - The 1984 national perinatal census: design, organization and uses for assessing obstetric services in Israel. AB - A nationwide perinatal census was conducted in Israel, in which medical, social, ethnic and demographic information on all births that took place in Israel within a predefined 3-month period was collected. The present study is the first to include 22,814 births that took place in all the obstetric units in Israel. The perinatal mortality rate decreased from 23.7 in 1964-68 to 13 in 1983-84. The frequency of cesarean section deliveries almost doubled over the last decade, while the use of forceps decreased significantly and the use of vacuum extraction did not change. The rate of low birthweight, however, remained constant over the last two decades. The level of hospital care has been shown to be significantly associated with perinatal mortality. The Israeli Perinatal Census may be used to provide information needed for promoting priority objectives for pregnancy and infant health, such as improving health status, identifying risk factors, increasing public and professional awareness, and improvement in services by protecting mother and fetus. PMID- 2592179 TI - A new, short family function assessment questionnaire for use in family medical practice in Israel: construction, validation and preliminary application. AB - This report describes the compilation and initial steps in the field testing of a new questionnaire intended for Israeli family physicians wishing to rapidly assess the general level of family functioning of their patients as part of everyday routine history taking in practice. The questionnaire was shown to have reasonable reliability and validity in a nonrepresentative sample of 140 married Israeli adults in three different family medicine practices. The questionnaire yielded a sum score ranging from 0 to 20. Preliminary estimates, based on a comparison of the sum score of each patient's questionnaire with the doctor's assessment of the family's functioning, suggest that patients of families with poor function score 11 or less, with satisfactory function 12 to 17, and with good function more than 17. These ranges require further refinement and standardization by testing the questionnaire among other groups of the Israeli population. PMID- 2592180 TI - Surgical removal of echocardiographically detected multiple pedunculated and mobile left ventricular thrombi in acute myocardial infarction. AB - Two-dimensional echocardiography revealed at least three left ventricular mural thrombi in a 59-year-old man with acute anterior myocardial infarction. The thrombi, which had highly mobile pedunculated elements, were attached to the septo-apical wall and protruded into the left ventricular cavity. In spite of the lack of a clinical event but in view of the potential risk of embolization, surgical removal of the thrombi was performed on the 16th day of hospitalization. PMID- 2592181 TI - The challenge to internal medicine. PMID- 2592182 TI - Relationship between iron accumulation and portal fibrosis. PMID- 2592183 TI - Acute glaucoma following nonophthalmic surgery. PMID- 2592184 TI - Teratoma of the head and neck in infancy. PMID- 2592185 TI - Intra-abdominal retained surgical gauze pad mimicking malignant tumor. PMID- 2592186 TI - Purpura fulminans associated with overwhelming sepsis and disseminated intravascular coagulation following splenectomy. PMID- 2592188 TI - Annual meeting of the Israel Society of Sports Medicine. 30 July 1989, Jerusalem, Israel. Abstracts. PMID- 2592187 TI - Transient histiocytic hemophagocytosis and pancytopenia in Mediterranean spotted fever. PMID- 2592189 TI - Street drugs. PMID- 2592190 TI - Street drugs: everyone's business. AB - In the profession of law enforcement, we see drug abuse as our most serious crime problem. We also realize that simply making arrests, by itself, won't solve the problem. The drug business might be the filthiest business on earth, but it's not a business that forces customers to buy dope. Dope dealers may be ruthless and may even kill, but no one forces anyone to buy drugs at gunpoint. The truth is that drug dealers would go nowhere, were it not for the customers. PMID- 2592191 TI - Crystal methamphetamine-induced acute pulmonary edema: a case report. AB - "Crystal methamphetamine" is a crystalline form of amphetamine, the abuse of which is growing rapidly in popularity in Japan, Hawaii and the West Coast. Drug experts and law enforcement officials say that the use of crystal meth is spreading east from California. It may produce permanent addiction and can produce violent schizophrenic behavior. Introduced along the Leeward Coast of Hawaii about 3 years ago, it is now being used throughout Oahu and is starting to rival cocaine as the illicit drug of choice in Hawaii. It is also the major drug problem in Japan, where the powder form is called "shabu." The smoking of crystal ("ice") in a glass pipe is more common in Hawaii, whereas other routes of administration, such as snorting or intravenous use, are more common on the West Coast. We present the case of a young woman who was admitted to Kaiser Moanalua Medical Center with near fatal acute pulmonary edema consequent to the use of crystal meth. PMID- 2592192 TI - Medical complications of the use of cocaine. AB - There are many serious medical problems that are associated with the use of cocaine and "crack" cocaine. PMID- 2592193 TI - Cocaine abuse and its treatment. AB - The abuse of cocaine has increased dramatically over the past 15 years. Studies performed by the National Institute of Drug Abuse (NIDA) revealed at least a five fold increase in its use from the mid-'70s to the late '80s. Recent reports indicated that at least 30 million Americans have tried cocaine and that 17% of high-school seniors have used cocaine on more than one occasion. It is estimated that there are 5,000 new users each day. Prevalence studies show that current use (use within the past 30 days) has increased to include at least 6 million Americans. Whereas studies over the past 2 years suggest some slowing of the dramatic increase mentioned above, the increase in the use of crack cocaine continues unabated. Recent political events in Central and South America are a clear reflection of the expanding demand for cocaine in both North America and Europe. PMID- 2592194 TI - Nicotine addiction. AB - Addiction to nicotine is the most common serious condition in medicine today. This chemical dependency has produced the largest epidemic of disease in this century, an epidemic that is beginning to wane in the United States but which is accelerating in the Third World. Widespread cultural acceptance of tobacco and the malignant fostering of use by cigarette merchants has perpetuated the epidemic. Nicotine regularly causes addiction in its users. This condition is best viewed as a chronic disease with remissions and exacerbations. It is highly amenable to treatment, and primary-care physicians are ideally situated to manage this fascinating condition. Physicians have a larger role to play, as well, in the many opportunities that exist to prevent this condition in the young and to protect non-smokers from tobacco smoke pollution. PMID- 2592195 TI - Referral patterns of elderly patients with dementia or depression. PMID- 2592196 TI - Geriatric psychiatry manpower--seven services in Scotland. AB - The method of calculating district psychiatric manpower described by Watson was applied to seven geriatric psychiatry services in Scotland serving a population of 1,445,000 including 209,600 individuals over the age of 65 years of age. The overall medical staffing of these services was only 63.6% of the estimated requirement and when individual consultants were considered only 62% of the necessary time was available. If it is assumed that half of the extra medical time should be provided by consultants, then 3.2 consultant WTEs will be needed for geriatric psychiatry for a population of 200,000 with 30,000 elderly people. If there was no change in the proportion of medical work provided by consultants, the figure would be 2.9 consultant WTEs per 30,000 population aged over 65 years. Extra supporting staff are also required to meet the requirements of the Watson formula. PMID- 2592197 TI - An audit of the adult hearing aid provision service in Scotland. AB - The need to monitor health service practice has never been more pressing. Three questionnaire surveys were carried out to assess the National Health Service (NHS) provision of hearing aids to adults in Scotland. The median wait between a letter requesting an opinion, including the suitability for a hearing aid, being received by a hospital, and a patient being seen by an otolaryngologist is eight weeks. After this there is a further median wait, primarily due to the necessity of manufacturing a permanent mould, of four weeks before they receive their final hearing aid complex. The easiest way to reduce the provision time is to improve the speed at which moulds can be manufactured. Lack of audiology technician posts could be a problem but the workload between departments varies considerably and requires evaluation. Almost certainly, better management strategies could be evolved. Otolaryngologists would appear interested in being responsible for the service and though many general practitioners (GPs) are also interested, the size of their practice would limit the number of aids that could be provided within the community. Open access to the existing hospital services should be investigated as a means of providing a more community orientated service. PMID- 2592199 TI - Minimal interventions with problem drinkers--a pilot study of the effect of two interview styles on perceived self-efficacy. AB - This study compares the effects of two differing interview styles on perceived self-efficacy in subjects receiving treatment for alcohol related problems. A 'Motivational Interviewing' Style was noted to have significantly increased situational confidence questionnaire (SCQ) scores when compared with scores from clients receiving 'Advice'. These differences conform with initial predictions and could have implications for clinical practice. Further research is suggested to test the applicability of these results under more rigorous conditions. PMID- 2592198 TI - A study of the incidence, the trend and the management of patients with ectopic pregnancies in the Scottish Highlands (1976-1987). PMID- 2592200 TI - Professional responses to alcohol related problems--a study of a health centre. PMID- 2592201 TI - The chief scientist reports ... hyperbaric oxygen for multiple sclerosis patients. AB - An 18-month uncontrolled study of the effects of hyperbaric oxygen therapy was conducted in 97 individuals with multiple sclerosis. Two-thirds of the patients were classified as progressive and one-third as stable. Assessment was based mainly on three aspects of activities of daily living: bladder function, mobility and communication. Bladder function showed a tendency to improve over the 12 month period of treatment but there was no evidence that treatment led to an improvement of mobility or communication. There are several reports of immediate improvement in bladder function, objectively and subjectively determined, in response to hyperbaric oxygen. In one study similar to that reported here, lack of deterioration in bladder function amongst progressive patients over two years, was related to continued hyperbaric oxygen treatment. PMID- 2592202 TI - Chernobyl source term, atmospheric dispersion, and dose estimation. AB - The Chernobyl source term available for long-range transport was estimated by integration of radiological measurements with atmospheric dispersion modeling and by reactor core radionuclide inventory estimation in conjunction with WASH-1400 release fractions associated with specific chemical groups. These analyses indicated that essentially all of the noble gases, 60% of the radioiodines, 40% of the radiocesium, 10% of the tellurium, and about 1% or less of the more refractory elements were released. Atmospheric dispersion modeling of the radioactive cloud over the Northern Hemisphere revealed that the cloud became segmented during the first day, with the lower section heading toward Scandinavia and the upper part heading in a southeasterly direction with subsequent transport across Asia to Japan, the North Pacific, and the west coast of North America. The inhalation doses due to direct cloud exposure were estimated to exceed 10 mGy near the Chernobyl area, to range between 0.1 and 0.001 mGy within most of Europe, and to be generally less than 0.00001 mGy within the United States. The Chernobyl source term was several orders of magnitude greater than those associated with the Windscale and TMI reactor accidents. However, the 137Cs from the Chernobyl event is about 6% of that released by the U.S. and U.S.S.R. atmospheric nuclear weapon tests, while the 131I and 90Sr released by the Chernobyl accident was only about 0.1% of that released by the weapon tests. PMID- 2592203 TI - Isotopic composition of high-activity particles released in the Chernobyl accident. AB - Gamma spectra were measured and activities of the detected isotopes were analyzed for 206 high-activity particles (hot particles, HPs) found in northeastern Poland after the Chernobyl accident. The isotopic composition of HPs observed in gamma activity is compared with that of the general fallout and core inventory calculations. Particle formation and a process of depletion in Ru and Cs isotopes are discussed. On the basis of a search performed a year later, some comments on the behavior of HPs in the soil are made. PMID- 2592204 TI - Evaluation of highly ionizing components in high-energy nucleon radiation fields. AB - The data and models for nuclear fragment recoil distributions produced by high energy nuclear events in tissue are reviewed. Results for linear energy transfer distributions in soft tissue are derived, and a simple model is developed for use in radiation studies and risk estimates. PMID- 2592205 TI - Population exposure from nuclear medicine procedures: measurement data. AB - In order to estimate the public radiation burden from nuclear medicine studies, a TLD chip in a sealed plastic bag was taped on the abdomen of patients who received 111In as chloride or oxine, 201T1 chloride, or one of four common 99mTc agents. The TLD chip was removed after 24 h. Additionally, abdominal skin surface exposure rate measurements were performed with an ionization chamber survey meter at various times (0 to about 60 h). There was superb correlation between TLD and integrated exposure rate measurements and between TLD and ionization chamber measurements and MIRD calculated doses. Scenarios postulated for exposure of co workers and family members yielded doses between 7 muSv (0.7 mrem) and 20 muSv (2 mrem) for the selected radiopharmaceuticals. Calculations of the total population exposure from nuclear medicine procedures indicate the per capita dose (amortized over the entire population) is approximately 0.4 muSv (0.04 mrem), a negligible dose compared to natural background and total medical irradiation. PMID- 2592206 TI - Determination of photon conversion factors relating exposure and dose for several extremity phantom designs. AB - Dosimetric measurements were performed to determine the exposure-to-dose conversion factors (Cx) for simple extremity phantoms suitable for extremity dosimeter performance testing. The phantoms studied represented the forearm or lower leg and the finger. Measurements were performed for solid plastic phantoms and for phantoms containing simulated bone material to determine the effect of backscattered radiations from the simulated bone to the phantom surface. Photon beam energies used for the measurements ranged from 16 keV to 1.25 MeV (average). The Cx factors for the finger phantoms did not vary significantly with phantom composition. The Cx factors in the arm/leg phantoms with the bone simulant material differed significantly from those for the solid plastic phantom over the energy range of 40-100 keV. This effect was attributed to the preferential absorption of the lower energy backscattered photons by the higher atomic number material that was contained in the bone-simulant insert. The position of the bone simulating material below the surface of the phantom was more important than its size or level of bone equivalency. For calibrations and dosimeter testing, Al was found adequate as a bone-simulating material. PMID- 2592207 TI - Improved counting efficiencies for measuring 239Pu in the lung in the sitting position. AB - For a study sponsored by the International Atomic Energy Agency (IAEA), Pacific Northwest Laboratory (PNL) made lung counting measurements of lung deposition in 10 women who had inhaled 92mNb in England. These women were measured in both the supine and sitting (torso 45 degrees from horizontal) positions with a counting system of Ge planar detectors and another counting system of Phoswich detectors. The average increase in counting efficiency from the supine to the sitting position was 108% for the Ge detectors and 310% for the Phoswich detectors. Individual counting efficiency increases ranged from 15-260% for the Ge detectors and from 40-480% for the Phoswich detectors. The increase in counting efficiency was roughly proportional to the total chest wall thickness of the measured individuals. By using the equivalent muscle tissue thickness of the individual's chest wall, the increase in counting efficiency could be attributed to the decrease in the tissue absorption in the sitting position. The decreased distance between the lungs and the detector achieved in the sitting positions may also account for some of the improvement in counting efficiency. In addition, some undetermined internal change in activity distribution (source-to-detector geometry) and tissue absorption may possibly contribute to the improved counting efficiency of the sitting vs. the supine position. PMID- 2592209 TI - Radium-226 content of beverages. AB - Radium contents of commercially obtained beer, wine, milk and mineral waters were measured. All distributions were log-normal with the following geometrical mean values: beer: 2.1 X 10(-2) Bq L-1; wine: 3.4 X 10(-2) Bq L-1; milk: 3 X 10(-3) Bq L-1; normal mineral water: 4.3 X 10(-2) L-1; medical mineral water: 9.4 X 10(-2) Bq L-1. PMID- 2592208 TI - Correlation among the terrestrial gamma radiation, the indoor air 222Rn, and the tap water 222Rn in Switzerland. AB - The external gamma radiation and the indoor air Rn (222Rn) concentration were measured in 55 houses of the South East Grisons, the Urseren valley, and the Upper Rhine valley (crystalline subsoils) and in 39 houses of the Molasse basin and the Helvetic nappes (sedimentary subsoils). In homes located on a crystalline subsoil, a mean cellar gamma level of 1.40 mGy y-1 was measured, which is twice the mean gamma level of 0.70 mGy y-1 found in homes built on a sedimentary subsoil. The cellar 222Rn gas concentration is about six times higher in houses with a crystalline subsoil (1232 Bq m-3) than in houses with a sedimentary subsoil (201 Bq m-3). Although a weak correlation is observed between the mean gamma radiation levels and mean cellar 222Rn gas concentrations for the five subregions investigated, the gamma levels and the 222Rn gas concentrations do not correlate for single homes. For the population living on the ground floor of a house with a crystalline subsoil, the gamma radiation and the indoor air 222Rn lead to estimated mean exposures of 1.16 mSv and 9.44 mSv effective dose equivalent per year, respectively. In houses with a sedimentary subsoil, these mean exposures lead to 0.68 mSv y-1 and 3.22 mSv y-1, respectively. A mean tap water 222Rn content of 38.3 Bq L-1 and 10.4 Bq L-1 was measured in 31 villages with a crystalline subsoil and 73 villages with a sedimentary subsoil, respectively. Radon-222 degasing from the tap water into the indoor air leads to an additional exposure of about 0.11 mSv y-1 and 0.03 mSv y-1 in homes with a crystalline subsoil and homes with a sedimentary subsoil, respectively. PMID- 2592210 TI - Assessment of radiological emissions from Spanish coal power plants: radioactive releases and associated risks. AB - The radioactivity of coals and ashes from Spanish coal power plants (CPP) was evaluated. This radioactivity is due mainly to 40K and the U and Th series. The samples were measured in secular equilibrium using a NaI(T1) detector. The annual average airborne releases were also evaluated. An atmospheric dispersion model was developed to predict the annual average concentration of radionuclides in air. The risks from inhalation were calculated and compared with those from nuclear power plants (NPP) and natural radioactivity. PMID- 2592211 TI - Results of a cleanup and treatment test at the Nevada test site: evaluation of vacuum removal of Pu-contaminated soil. AB - We have conducted experiments to evaluate the effectiveness of removing contaminated soils from the Nevada Test Site with a large truck-mounted vacuum cleaner. Our results show that this method is effective, relatively easy, and safe for equipment operators. With four passes of the truck-mounted vacuum, 92% of the 241Am (and the accompanying 239 + 240Pu) was removed and resuspension rates were reduced by more than 99%. The ecological impact was, however, serious in terms of soil erosion and destruction of small animal habitats. Compared to standard earth-moving techniques, vacuuming permits a significant reduction in the volume of soil collected to achieve the desired level of decontamination, and the volume reduction could result in cost savings for packaging, shipment, and burial. This cost savings would only be realized for projects involving decontamination of the top 5 cm of soil. PMID- 2592212 TI - Effect of redox potential on fixation of 137Cs in lake sediment. AB - Fixation of 137Cs was determined in lake sediment suspensions under controlled redox potentials in the laboratory. The activity of previously added 137Cs on various clay sites was determined by time-series selective extractions. Monovalent cations, particularly NH+4, were much more effective at displacing 137Cs than divalent cations or Na+. Ammonium ion (NH+4) and Na+ were used to extract 137Cs from selective and non-selective 137Cs-binding sites, respectively. The activity of water-soluble 137Cs and Na-extractable 137Cs was significantly higher under anaerobic redox conditions (-200 mV), when soluble NH+4 concentrations in the anaerobic suspensions were 1000 microM or higher. Activities of 137Cs were highest (initially 40-50% of the 137Cs added) on the NH+4-extractable site. Over the long term, activities of NH+4-extractable 137Cs decreased linearly to below 10% as 137Cs was fixed on inter-lattice sites. Water soluble 137Cs was significantly correlated with Na-extractable 137Cs in short term experiments, suggesting the existence of an equilibrium between the different clay sites. High concentrations of NH+4 under anaerobic redox conditions could shift this equilibrium, resulting in increases in water-soluble 137Cs and increases in the activities of 137Cs bound on non-selective clay sites. Additional studies are necessary to evaluate the interaction of 137Cs with sulfides, iron oxides, and other reactive chemical species which may attenuate 137Cs in sediment. PMID- 2592213 TI - Role of various microorganisms on Tc behavior in sediments. AB - Marine bacteria (Moraxella sp., Planococcus sp. and a mixed population of anaerobes) from a coastal sediment were found to concentrate Tc. Maximum concentration of this element occurred during the stationary phase of growth of the bacteria, at low redox potential. A metabolic process seems responsible for Tc concentration by bacteria, in which it binds to high molecular weight cellular constituents. Polysaccharidic polymers, which were visualized around the bacterial cells with the scanning electron microscope, might bind Tc, but direct experimental evidence in favor of this hypothesis was not yet obtained. The role of sedimentary bacteria in the behavior of Tc in the marine environment is briefly discussed. The action of sulfate-reducing microorganisms is considered. PMID- 2592214 TI - A charcoal coil measurement system for environmental 222Rn. PMID- 2592215 TI - Experimental measurement of angular dependency of external dose from 40 keV x-ray photons. PMID- 2592217 TI - Studies of the neutron transport and shielding properties of locally developed shielding material: poly-boron. PMID- 2592216 TI - Scattered radiation levels from a portable fluoroscopic/angiographic unit. PMID- 2592218 TI - An inexpensive miniaturized linear CdTe detector array system. PMID- 2592219 TI - Europium-152 activity induced by Hiroshima atomic bomb neutrons: comparison with the 32P, 60Co, and 152Eu activities in dosimetry system 1986 (DS86). PMID- 2592220 TI - Need for international forum on space personnel dosimetry. PMID- 2592221 TI - Mortality of Hanford workers. PMID- 2592222 TI - Reply to radiation cancer risk series. PMID- 2592223 TI - Protocol for indoor 222Rn measurements. PMID- 2592224 TI - Abnormal concentration of U in many brands of South American cigarette tobacco. PMID- 2592225 TI - A position of strength. PMID- 2592226 TI - Shades of opinion: members' thoughts on merger partners. PMID- 2592227 TI - My decision to resign by Shirley Goodwin. PMID- 2592228 TI - All about me: a parent-completed development profile. PMID- 2592229 TI - Whither health visiting: a PR exercise? PMID- 2592230 TI - The detection of emotional disorders in the post natal period by health visitors. AB - One hundred mothers of six week old babies were screened for emotional disorders using the general health questionnaire (GHQ). The effect on health visitors' client management was assessed over a nine month follow-up period, using a controlled trial approach. The findings indicate that screening for symptoms of minor psychiatric disorder at six weeks post partum would assist health visitors to give extra support to those mothers who are most in need of it. PMID- 2592231 TI - Setting up a parenting group. AB - An account of a project encouraging the individual's responsibility for his/her own health; the health of offspring; and the social implications for responsible self-care. The 'parenting group' is intended to provide a centre of information and knowledge to assist and develop the ability and skills of parents and carers of young children. PMID- 2592233 TI - Talking about how difficult we find it. AB - As part of a study on the health and social support needs of families with a baby aged under one year, twenty families on Merseyside with a baby born in the same month in 1988 were interviewed at home when the baby was between seven and nine months old. The interviews were unstructured, tape recorded and later transcribed in full. Transcripts were indexed to explore the need for, use of and response to, health support systems. Most interviewees felt that post-natal groups would provide valuable support. PMID- 2592232 TI - The emotional state of mothers in the first three months after the birth of their baby. AB - A questionnaire was sent to the 98 health visitors who had taken part in the postnatal questionnaire study, asking them for comments on its difficulties and benefits. In their answers they referred to their staffing difficulties, the mothers' language problems, doubt about the truthfulness and accuracy of the mothers' replies to their questionnaire, and to difficulties experienced in liaison with family doctors, hospital psychiatric units, social workers and other social services. Of the 69 health visitors who replied to the questionnaire, 48 (70 per cent) thought that the study had been helpful, 14 had mixed feelings and six replied in the negative. There was little doubt that the postnatal questionnaire study had greatly increased the health visitors' understanding of maternal emotional problems and depression, and the difficulties of helping the mothers. It helped the mothers to understand more of their own feelings, and to discuss them with the health visitors in order to seek advice. PMID- 2592234 TI - Your rights at work. When is a bank not a bank? Part-time holiday blues. PMID- 2592235 TI - Tracheostomy care in an educational setting. AB - An account of the key role of a school nurse in caring for a child with a tracheostomy. PMID- 2592237 TI - School nursing in Norwich Health Authority. AB - The aim of this article is to outline the school nurse's role in Norwich Health Authority which appears to be providing one of the most comprehensive services of any health authority. PMID- 2592236 TI - The changing role of the school nurse within Worcester and District Health Authority. AB - An account of the key role of a school nurse in caring for a child with a tracheostomy. PMID- 2592238 TI - Trade unionists refuse toxic waste. PMID- 2592239 TI - At risk drinkers. PMID- 2592240 TI - Helping mothers with post-natal depression. PMID- 2592241 TI - Pain assessment: an interdisciplinary perspective. AB - Pain is a very real problem affecting a large percentage of patients in home care settings. Pain has no mercy, and does not discriminate by age or condition. Although pain is often initiated by an organic condition (primary diagnosis), this trigger situation can produce multiple primary pain. Contrary to some common belief, medication or bed rest or reduction of physical activity is not always effective or indicated in some types of biomechanical pain, for example, neck, shoulder, low back, contractures. How people feel about themselves, how they see themselves fitting into the scheme of life as a purposeful and contributing member who has worth and value, has a powerful influence on how they perceive and manifest pain. When a person is allowed to work collaboratively with the interdisciplinary team in setting goals, compliance with treatment regimens is likely to be considerably higher. As health professionals we have a responsibility that we all take very seriously: to provide the best and most appropriate care for our patients. When working in collaboration with each other, this goal can be realized. PMID- 2592242 TI - Reviewing your patient's medication regimen: a systematic approach. AB - To ensure that your patients' medications do not create more problems than they solve, examine all medications being taken, whether prescription or not. Review each drug regimen in a systematic manner, noting history of adverse effects, need for the drug, duplication in therapy, inappropriate dose, route, or schedule, current adverse effects, drug-drug interactions, and drug-disease interactions. Doing so will help you identify or prevent problems. It can also highlight ways in which the medication regimen may be simplified. The patient's pharmacist can be an excellent resource for determining appropriate dosages, potential for interaction, and overlapping drugs. Unnecessary or potentially dangerous medications can be brought to the attention of the physician and perhaps eliminated, simplifying the regimen and possibly increasing compliance. You will be more alert to possible adverse reactions, and have a clearer understanding of your patient's medication therapy. PMID- 2592243 TI - Cancer patients at home: needs and coping styles of primary caregivers. AB - Clearly, this group of caregivers were using some problem-oriented coping methods (ie, confrontive in the Jalowiec Scale). Nevertheless, they experienced great concern in dealing with the side effects of treatment and in alleviating the patient's pain. They expressed their anxiety and their fears and their inability oftentimes to cope. They did not utilize community resources and for the most part were isolated in their homes except for those who were employed. There was concern expressed for needing some timeout away from caretaking activities and for keeping their own outlook healthy. The need for personal strength was mentioned often. PMID- 2592245 TI - Adjusting to the diagnosis of cancer: the healthiest way of being ill. PMID- 2592244 TI - Listening to families. PMID- 2592247 TI - Shared patients. PMID- 2592246 TI - Referral by facsimile: new legal headache for home health care? PMID- 2592248 TI - Cytophotometric analysis of enzyme reaction rates in tissue sections. PMID- 2592249 TI - The use of continuous monitoring and computer-assisted image analysis for the histochemical quantification of hexokinase activity. AB - The effect of endogenous 6-phosphogluconate dehydrogenase (6PGDH) on the histochemical quantification of low-Km hexokinase activity in rat submandibular salivary glands has been investigated using a Seescan Solitaire Plus image analysis system and a modified black and white Newvicon TV camera. Absorbance readings of neutral density filters were close to their known absorbance values. A significant correlation was found between the absorbance of Nitro BT reduction products within sections, with and without the use of a 588 nm interference filter. Furthermore, absorbance readings obtained from 8 microns-thick sections were 1.92 and 2.22 times greater than values obtained from 4 microns-thick sections using 'white' and 588 nm light respectively. The level of background illumination was not critical for absorbance measurements provided it was below the level that saturated the Newvicon camera and was not changed between background and image capture. The greatest variations in absorbance readings on tissue sections were associated with changes in zoom and objective combinations. Our studies indicate that this relatively low cost image analysis system can give reproducible absorbance readings from various structures defined in digitized, captured images of tissue sections. Results from continuous monitoring studies indicated that the high levels of 6PGDH activity in excretory ducts caused a 1.67 fold overestimation of hexokinase activity as assessed by absorbance readings performed throughout a 22-minute reaction period. By contrast, overestimation of hexokinase activity in salivary gland acini only became apparent after 8 min incubation with a 1.4-fold overestimation being seen at 22 min. This difference appears to reflect the relatively low hexokinase and 6PGDH activities present in acini compared with excretory ducts. PMID- 2592250 TI - The 'nothing dehydrogenase' reaction and the detection of ischaemic damage. AB - The 'nothing dehyrogenase' reaction is defined as the reduction of tetrazolium salts in media lacking specific substrates for dehydrogenases. In this investigation, the kinetics of the 'nothing dehydrogenase' reaction were studied in cryostat sections of rat heart and liver with the use of various polyvinyl alcohol-containing incubation media. Formazan production was measured at 585 nm with a cytophotometer. The 'nothing dehydrogenase' reaction was substantially lower in the heart than in the liver which was due to low levels of endogenous lactate and the absence of proteins containing thiol groups, such as albumin, in the heart. In vitro ischaemia resulted in a reduced 'nothing dehydrogenase' reaction due to loss of NAD+, possibly as a consequence of its breakdown by glycohydrolase activity. One hour reperfusion following one hour ischaemia caused a decreased 'nothing dehydrogenase' reaction in certain areas of the liver. This reduction was a result of leakage of lactate dehydrogenase and thiol-containing molecules. It appeared at the ultrastructural level that parenchymal and endothelial cells were heavily damaged in the areas containing a low 'nothing dehydrogenase' activity. In conclusion, early ischaemic damage in liver can be detected with the 'nothing dehydrogenase' reaction. PMID- 2592251 TI - Cytophotometric analysis of reaction rates of succinate and lactate dehydrogenase activity in rat liver, heart muscle and tracheal epithelium. AB - Reaction rates of succinate and lactate dehydrogenase activity in cryostat sections of rat liver, tracheal epithelium and heart muscle were monitored by continuous measurement of formazan formation by cytophotometry at room temperature. Incubation media contained polyvinyl alcohol as tissue protectant and Tetranitro BT as final electron acceptor. Control media lacked either substrate or substrate and coenzyme. Controls were also performed by adding malonate (a competitive inhibitor of succinate dehydrogenase), pyruvate (a non competitive inhibitor of lactate dehydrogenase), oxalate (a competitive inhibitor of lactate dehydrogenase) or N-ethylmaleimide (a blocker of SH groups). A specific malonate-sensitive linear test minus control response for succinate dehydrogenase activity was obtained in liver (1.6 mumol H2cm-3 min-1) and tracheal epithelium (0.8 mumol H2cm-3 min-1) but not in heart muscle. All variations in the incubation conditions tested did not result in a linear test minus control response in the latter tissue. Because the reaction was sensitive to malonate, it was concluded that the initial reaction rate was the specific rate of succinate dehydrogenase activity in heart muscle (9.1 mumol H2 cm-3 min 1). Test minus control reactions for lactate dehydrogenase activity were distinctly non-linear for all tissues tested. This appeared to be due to product inhibition by pyruvate generated during the reaction and therefore it was concluded that the appropriate control reaction was the test reaction in the presence of 20 mM pyruvate. The initial rate of the test minus this control was the true rate of lactate dehydrogenase activity. The lactate dehydrogenase activity thus found in liver parenchyma was 5.0 mumol of H2 generated per cm3 liver tissue per min. PMID- 2592252 TI - In situ kinetic parameters of glucose-6-phosphate dehydrogenase and phosphogluconate dehydrogenase in different areas of the rat liver acinus. AB - The reaction velocity of glucose-6-phosphate dehydrogenase (G6PDH) and phosphogluconate dehydrogenase (PGDH) was quantified with a cytophotometer by continuous monitoring of the reaction product as it was formed in liver cryostat sections from normal, young mature female rats at 37 degrees C. Control incubations were performed in media lacking both substrate and coenzyme for G6PDH activity and lacking substrate for PGDH activity. All reaction rates were non linear but test minus control reactions showed linearity with incubation time up to 5 min using Nitro BT as final electron acceptor. End point measurements after incubation for 5 min at 37 degrees C revealed that the highest specific activity of G6PDH was present in the intermediate area (Vmax = 7.79 +/- 1.76 mumol H2 cm-3 min-1) and of PGDH in the pericentral and intermediate areas (Vmax = 17.19 +/- 1.73 mumol H2 cm-3 min-1). In periportal and pericentral areas, Vmax values for G6PDH activity were 4.48 +/- 1.03 mumol H2 cm-3 min-1) and 3.47 +/- 0.78 mumol H2 cm-3 min-1), respectively. PGDH activity in periportal areas showed a Vmax of 10.84 +/- 0.33 mumol H2 cm3 min-1. Variation of the substrate concentration for G6PDH activity yielded similar KM values of 0.17 +/- 0.07 mM, 0.15 +/- 0.13 mM and 0.22 +/- 0.11 mM in periportal, pericentral and intermediate areas, respectively. KM values of 0.87 +/- 0.12 mM in periportal and of 1.36 +/- 0.10 mM in pericentral and intermediate areas were found for PGDH activity. The significant difference between KM values for PGDH in areas within the acinus support the hypothesis that PGDH is present in the cytoplasmic matrix and in the microsomes. A discrepancy existed between KM and Vmax values determined in cytochemical assays using cryostat sections and values calculated from biochemical assays using diluted homogenates. In cytochemical assays, the natural microenvironment for enzymes is kept for the demonstration of their activity and thus may give more accurate information on enzyme reactions as they take place in vivo. PMID- 2592253 TI - Rapid continuous monitoring of enzyme activity in tissue sections: experience with the M85A and Zeiss UMSP-30 systems. AB - We have previously described methods for the continuous monitoring of formazan deposition in tissue sections with a system based on the Vickers M85A microdensitometer. However, this instrument only allows the monitoring of a single field in each section. We have now developed a new system based on the Zeiss UMSP-30 microspectrophotometer. This machine is entirely computer controlled and by virtue of its fast-scanning stage allows the rapid (less than 0.5 s) sequential monitoring of multiple fields (up to 35) in each section. Thus a number of cell types may be studied simultaneously and work which used to take a full working day with the M85A system now can be performed in 45 min. As with the M85A the Zeiss system has full capability for data analysis (i.e. calculation of initial velocity rates, etc.). We have found that continuous monitoring of tissue sections by microdensitometry is a precise, sensitive and biochemically valid method of studying enzyme activity within the cellular matrix. PMID- 2592254 TI - Cytochemical analysis of single villus peptidase activities in pig intestine during neonatal development. AB - The present work uses a new technique of whole tissue cytochemistry and automated scanning to obtain measurements of peptidase activity and surface structure in intact villi microdissected from the jejunum of newborn and 28-day-old pigs. Intact villi from 28-day-old pigs are shown by this method to contain 30% more aminopeptidase N and 400% more dipeptidylpeptidase IV activity than is found on villi taken from newborn pig intestine. Villi taken from 28-day-old pig intestine are also half as long and twice as wide at their base as those taken from newborn animals. These changes in shape take place without significantly affecting the total surface area of the villus. Increases in peptidase activities occurring during postnatal development can be further subdivided into those dependent upon induced changes in enterocyte biochemistry and those dependent upon the changing geometry of villi. Over 90% of the total increase in peptidase activities occurring during neonatal development was shown, by this analysis, to involve enterocyte reprogramming of enzyme production. The present method of whole tissue cytochemistry appears to combine successfully the ability to measure peptidase activities at the cellular level in undisrupted tissue with a facility to relate these results to the overall shape of a single villus. These and more general applications of the method now provide new ways to analyse a variety of changes taking place in intestinal structure and function in a quantitative manner. PMID- 2592256 TI - [Delivery in a delivery chair--experiences of mothers and midwives]. PMID- 2592257 TI - [Interview study among mothers with cesarean section]. PMID- 2592255 TI - Plateau absorbance measurements: an alternative approach to enzyme activity determination illustrated by the example of alkaline phosphatase. AB - A simple and reproducible method was used for the cytophotometric assay of alkaline phosphatase activity by end point measurements after incubation at 70 degrees C. Alkaline phosphatase was incorporated in polyacrylamide gel model films and its activity was demonstrated with a simultaneous coupling method. The initial reaction rate was 4.7 times faster than at 37 degrees C. At 37 degrees C, linear reaction rates were obtained up to 90 min incubation. Deviation from linearity occurred only when the amount of final reaction product precipitated inside the films was too high to be measured cytophotometrically. In that case, levelling off of the reaction rate was due to the out-of-range error of the cytophotometer. At 70 degrees C, reaction rates were distinctly non-linear from the onset of incubation. This was due to heat inactivation of the enzyme molecules. A plateau level was reached after approximately 60 min incubation, irrespective of the amount of enzyme incorporated, indicating that all enzyme molecules had become inactivated after this incubation period. The inactivation process followed first-order kinetics. The plateau value as well as the slope of the initial reaction were found to be linearly related to the amount of enzyme incorporated. Therefore, plateau absorbance values can be used as a relative measure of enzyme activity instead of initial reaction rates. This type of measurement could be valuable for routine applications of enzyme cytochemistry in diagnostic pathology, or when cytochemical reaction products are used as markers in immunocytochemistry or hybridocytochemistry. Precise control of incubation time is not necessary once the plateau value has been reached and preparations can be mounted and measured later. PMID- 2592258 TI - [Description of the way from a Danish authorized midwife to a Swedish certified midwife--continuation]. PMID- 2592259 TI - [Travel report from the USA]. PMID- 2592260 TI - [Travel report from an ABC clinic in Washington]. PMID- 2592261 TI - [Sarasota Birthing House, Florida]. PMID- 2592262 TI - [Scholarship award "HIV--AIDS"]. PMID- 2592263 TI - [Scholarship report about study trip to the USA]. PMID- 2592264 TI - [Scholarship report from the study days at the RFSU clinics on the subject of STD]. PMID- 2592265 TI - Mast cells in the testis, epididymis and accessory glands of the rat: effects of neonatal steroid treatment. AB - Mast cells in the testis of control adult rats were found almost exclusively around subcapsular blood vessels. Discrete mast cells were distributed throughout the stroma of the epididymis and sex accessory glands. In neonatally estrogen treated rats, a greater number of mast cells was present in the testicular interstitium, whereas no significant increase in the number of mast cells per square millimeter of stroma was found for the epididymis and sex accessory glands, despite stromal proliferation. On the other hand, androgen-treated rats did not have increased mast cell numbers in any organ. These results indicate that the increase in mast cell numbers was estrogen-dependent, specifically related to the testis and did not seem to be a consequence of the increase in the connective interstitial tissue. PMID- 2592267 TI - Quality control during the conventional analysis of semen, an essential exercise. AB - Intra- and inter-technician variability in assessing sperm motility by the methods recently advocated by the World Health Organization (WHO) were studied. The intra- and inter-technician variability in estimating sperm concentration and the intra-technician variability in assessing sperm morphology were also examined. Intra-technician variability in assessing sperm motility appeared to be related to the natural ability and/or training of the observer. Although in general the intra-technician variability was low, there were marked and clinically significant differences between observers when assessing the same semen sample. There was no significant difference between observers in the assessment of sperm concentration, and intra-technician variability was low. When assessing sperm morphology, the intra-technician variability was potentially large (above a level of 20% morphologically ideal spermatozoa). Technicians should be recruited who have natural ability as observers. Quality control appears to be an essential exercise for any center that plans to relate semen parameters to fertility outcome. PMID- 2592266 TI - Circadian variation in testosterone, sex hormone-binding globulin, and calculated non-sex hormone-binding globulin bound testosterone in healthy young and elderly men. AB - The circadian pattern in levels of serum total testosterone (T) in men becomes blunted with normal aging. However, because T not bound to sex hormone-binding globulin (non-SHBG-T) is felt to be a better representative of biologically available T than is total T, the possibility of a 24-h variation in non-SHBG-T in young men and the possibility that aging is associated with a blunting of that rhythm were investigated. Hourly blood samples were drawn on 10 normal young men (mean age 27.3 years) and 10 normal elderly men (mean age 70.7 years) over a 24-h period and the serum was assayed for total T, sex hormone-binding globulin (SHBG), and total protein; non-SHBG-T was calculated. SHBG was determined by radioimmunoassay as well as by a steroid-binding assay. Young men had a significantly higher (p less than 0.05) mean 24-h level of non-SHBG-T (1.91 +/- 0.62 nm/l) than did the elderly men (0.86 +/- 0.01 nM/l). Also, each young man showed a significant circadian rhythm in non-SHBG-T, with a group mean daily variation of 1.42 +/- 0.38 nM/l. In contrast, only 60% of the elderly men demonstrated a significant circadian rhythm in non-SHBG-T, and the group mean rhythm was blunted (maximum excursion 0.38 +/- 0.07 nM/l) compared with that of the young men. SHBG and total protein levels demonstrated similar 24-h variations in the two age groups. It was concluded that non-SHBG-T serum levels, similar to serum total T levels, demonstrate a circadian pattern in young men and this circadian rhythmicity becomes blunted with normal aging. PMID- 2592268 TI - Vasopressin receptors in human seminal vesicles: identification, pharmacologic characterization, and comparison with the vasopressin receptors present in the human kidney. AB - Because of the presence of a high density of vasopressin receptors in the epithelial cells of porcine seminal vesicles similar to the V2 vasopressin receptors of renal tubules, human seminal vesicles and kidney were investigated using quantitative binding and adenylate cyclase studies. Tissues were obtained at surgery from 17 patients with urologic diseases. A homogeneous class of vasopressin binding sites have been found in both seminal vesicles and renal medulla. However, the vasopressin receptors present in these tissues are different in terms of ligand specificity and adenylate cyclase activation. In seminal vesicles, the V1 vasopressin antagonist d(CH2)5 TyrMeAVP is 36-fold, more potent than the V2 agonist dVDAVP in displacing [3H]AVP binding, while in the medullopapillary portion of kidney dVDAVP is 24-fold, more selective than d(CH2)5 TyrMeAVP for the arginine vasopressin binding site. Furthermore, arginine vasopressin induces a dose-dependent increase in adenylate cyclase activity in renal membranes, while it was ineffective in seminal vesicle membranes. These results indicate that a very high affinity (0.2 nM), low capacity (14 fmoles/mg protein) class of vasopressin receptors is present in human seminal vesicles, having pharmacologic characteristics similar to the V1 subtype of vasopressin receptors. The presence of a high affinity (1.6 nM), high capacity (350 fmoles/mg protein) V2 subtype of vasopressin receptors in human renal membranes is also confirmed. The density of the vasopressin receptors present in human seminal vesicles is inversely correlated with patient age, consistent with a physiologic role for vasopressin in the regulation of accessory sex gland activity. PMID- 2592269 TI - The automated analysis of rat sperm motility following subchronic epichlorohydrin administration: methodologic and statistical considerations. AB - The automated analysis of sperm motion endpoints is potentially useful in identifying male reproductive toxicants and ultimately in predicting fertility in humans. The present study was designed to evaluate the automated analysis of rat sperm motility characteristics following subchronic administration of epichlorohydrin. This type of validation is a prerequisite for inclusion of sperm motion measurements in the process of reproductive risk assessment. In the present studies videotapes were made of cauda epididymal spermatozoa from Long Evans rats, both untreated and treated with epichlorohydrin. From analysis of videotapes of control epididymal spermatozoa, the relationship of various sperm motion endpoints and settings of the CellSoft computer-assisted sperm motion analysis system (Cryo Resources, Ltd., New York, NY) is described. Optimal settings of the system for analysis of rat spermatozoa are detailed. Employing data from both control and epichlorohydrin-treated animals, a statistical methodology is described that evaluates: (1) the distributions of CellSoft generated sperm motion endpoints, (2) the correlations between these endpoints, and (3) techniques for detection of dose-related effects. PMID- 2592270 TI - The influence of mineral supplementation on growth and skeletal development of yearling horses. AB - Forty-six Thoroughbred and Quarter Horse yearlings were used in two experiments to evaluate the effect of mineral supplementation on growth and skeletal development. In the first experiment, concentrate and bermuda-grass hay diets providing 2.82 Mcal DE/kg (estimated), 13.0% CP, .62% Ca and .43% P on a DM basis were supplemented with trace minerals (TM) by adding 0, .5 or 1.0% TM premix to the concentrate. The TM content of the three diets (concentrate and hay) in mg/kg DM were: Fe 150, 162 and 176; Mn 56, 60 and 64; Zn 36, 53 and 69; and Cu 7, 8 and 11 for the low, medium and high TM levels, respectively. No effects of TM intake on feed intake, weight gain or body measurements were detected, but bone mineral deposition was increased by the high TM intake (P less than .02). No gross skeletal abnormalities were detected. In the second experiment, a basal diet with Ca and P concentrations near NRC (1978) recommendations was supplemented with no TM, TM or TM + Ca + P. The basal diet had TM concentrations similar to the highest TM levels in the first experiment. The two groups fed added minerals consumed more concentrate and total feed (P less than .1) than those receiving the basal diet. Weight gain was increased by the TM supplementation (P less than .1). There was no other diet effect on growth or development of the animals. Colts gained more height than fillies did (P less than .05). Results of these two experiments suggest that TM supplementation may have a positive effect on bone mineral deposition in yearling horses, but only when the TM content of the natural diet is below NRC (1978) recommendations. PMID- 2592271 TI - Crossbreeding among British and continental European dual-purpose breeds in the coastal Pacific Northwest. AB - From 1979 through 1987, British breed and crossbred cows were mated to Simmental, Pinzgauer or Tarentaise bulls or to Hereford-Angus crossbred bulls. Beginning in 1982, continental European crossbred females also entered the herd, to be mated for first calving to Hereford-Angus or Angus bulls and as cows to continental European or Hereford-Angus bulls. In progeny of British breed and crossbred cows, dam breed effects on birth and weaning weight were not important, but continental European crossbred calves were heavier than British crossbred contemporaries at birth and weaning. Pinzgauer- and Simmental-sired calves were heavier at birth than Tarentaise crosses, but calves sired by each of the continental breeds had similar weaning weights. Maternal heterosis was greater than direct heterosis effects on weaning weight (8% vs 5%), but only direct heterosis (13%) influenced birth weight. Within progeny of continental European crossbred cows, calves with a Tarentaise maternal grandsire were lighter at birth, with no significant difference among other maternal grandsire breeds. Maternal breed effects on weaning weight were not significant. Nevertheless, in contemporary years, continental European crossbred cows reared calves that were 10% heavier than calves reared by British crossbred cows. Pacific Northwestern cattle producers could achieve substantial increases in weaning weight from introducing inheritance from continental European dual-purpose breeds into cow herds and calf crops of British ancestry. PMID- 2592272 TI - Breeding performance of beef bulls assigned to two-sire cow groups on pasture. AB - Angus, Polled Hereford and Santa Gertrudis bulls from ages 1 through 5 and 7 yr were assigned to 26 two-sire breeding groups. Each year, straightbred and crossbred cows of these breeds were allotted at random within breed composition, age of dam and calving date to breeding groups on pasture. Sires within each breeding group or pair were the same age at breeding and were two of the three breeds of sires. Neither calving rate nor the proportion of calves born by one vs the other sire in the two-sire breeding groups was affected by sire age among breeding groups. For a given breed, there was no uniformity among the sires in the proportion of calves they sired in their two-sire breeding groups. The proportion of calves born for the 26 sire pairs averaged .64 vs .36 (SE = 0.4 for either high or low value) for one vs the other sire in a sire pair with no indication that calving rate was affected by unequal proportions of calves by sires within sire pairs. Cows calved significantly earlier in the calving period (b = -.775 +/- .127) as calving rate increased among sire pairs. The number of days from the start of the breeding period to calf birth was affected by differences between sires in sire pairs for 8 of the 26 pairs, but there were no significant differences due to sire pair or breed of sire because of interaction between these two variables. PMID- 2592273 TI - Intake and digestibility of low-quality meadow hay by cattle receiving various levels of whole shelled corn. AB - Two trials were conducted to evaluate the effects of whole shelled corn supplementation on intake and digestibility of low-quality meadow hay by cattle. In Trial 1, four ruminally cannulated steers (avg BW 418 kg) were used in a latin square design with four treatments (no corn or corn fed at .25%, .50% or .75% of BW). Hay DMI decreased (P = .002) linearly .43 g for each gram of increase in corn intake. In contrast, total diet DMI increased (P = .001) linearly as level of corn supplementation increased. Apparent DM digestibility of the diet increased (P = .026) linearly, whereas hay DM digestibility was not affected (P greater than .05) by supplemental corn, although the DM digestion coefficient for hay alone was 24% higher than for hay fed with corn at .75% of BW. Ruminal ammonia concentration and pH were not affected (P greater than .05) by treatments; however, ratio of acetate:propionate and acetate:butyrate responded (P less than or equal to .097) quadratically to increased corn supplementation. Corn supplementation resulted in a cubic (P less than or equal to .081) decrease in meadow hay NDF disappearance from nylon bags suspended in the rumen at all incubation intervals after 4 h. In Trial 2, 45 crossbred, nonlactating, pregnant cows (avg BW 474 kg) were used in a completely randomized design with three treatments (no corn, .91 and 1.81 kg corn.hd-1.d-1). Cow performance was not altered (P greater than .05) by treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592274 TI - Multiple ovulation and embryo manipulation in the improvement of beef cattle: relative theoretical rates of genetic change. AB - Theoretical rates of annual genetic responses to selection in beef cattle were compared for conventional and multiple ovulation and embryo transfer (MOET) breeding schemes. Several combinations of replacement policy, mating ratio and type of selection were considered for both schemes with low, medium and high heritabilities. For MOET, four rates of embryo transfers per donor were used to represent low to moderate MOET levels. The results indicated that annual genetic responses to selection could be up to 1.3, 1.6 and 1.8 times as great for MOET compared with conventional breeding for traits of low, medium and high heritability, respectively; however, the annual inbreeding rates also were high for the MOET schemes considered. Embryo splitting, or cloning, was shown to increase accuracy of selection by 8 to 35% through the production of identical genotypes. The use of MOET in conjunction with embryo splitting in elite nucleus units could substantially increase genetic improvement for traits with low, medium and high heritabilities in beef cattle populations. PMID- 2592275 TI - The relationship of insulin-like growth factor-I with postweaning performance in Angus beef cattle. AB - This study was designed to evaluate the ontogeny of serum IGF-I (SI) concentrations and its relationship to animal performance in a 140-d postweaning feeding trial. Ninety-eight progeny representing six sires (three high and three low feed conversion) and two sexes (43 bulls and 55 heifers) with ad libitum access to feed were allocated by sire and sex to monitor individual weights and pen feed consumption. Blood serum samples were obtained at the beginning of test (average age of 230 d) and every 28 d thereafter until each animal reached a fat thickness (estimated by sonoray) of 8.9 mm. Individual serum samples were acid ethanol extracted and measured for IGF-I peptide by heterologous RIA. Serum IGF-I concentrations differed (P less than .10) between high (H) and low (L) feed conversion progeny groups at the end of the first 28-d period (125.12 vs 89.52 ng/ml) and tended to differ at the conclusion of the second 28-d period (P less than .15). Weight gains of H and L groups tended to differ in the second and third 28-d periods (P = .11 and .10, respectively). Serum IGF-I concentrations differed (P less than .05) between bulls and heifers for the first through fourth 28-d periods (P less than .01, P less than .05, P less than .10 and P less than .01, respectively). Phenotypic correlations indicated that pens with higher mean SI concentrations at the beginning of the test consumed less feed and had lower cumulative feed:gain ratios.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592276 TI - Relationships of sire scrotal circumference to offspring reproduction and growth. AB - Reproductive and growth data were obtained on 779 and 564 yearling beef heifers and bulls, respectively, that had sires with yearling scrotal circumference data at the San Juan Basin Research Center, Hesperus, CO. Partial regression coefficients of reproductive and growth traits on inbreeding (FXC) and age of the individual and adjusted scrotal circumference of sire (SCSI) were obtained. Growth and reproductive traits of heifers and growth and breeding soundness traits of bulls were analyzed. Separate analyses for each sex were performed, but least squares models were similar. Models included fixed effects of breed, birth year (BY), age of dam (AOD) and the covariates FXC, age (day of birth in heifer analyses) and SCSI. Scrotal circumference of sire was adjusted for age, FXC, AOD and BY using values obtained in a separate analysis. Seminal traits improved as age increased, and there was a seasonal effect present for age of puberty. Inbreeding had a detrimental effect on reproductive traits. Partial regression coefficients for the reproductive traits on SCSI were: age of puberty, -.796 d/cm; age of first calving, -.826 d/cm; julian day of first calving, -.667 d/cm; julian day of second calving, .597 d/cm; most probable producing ability, .132 %/cm; percent sperm motility, -.74 %/cm; percent primary sperm abnormalities, .08 %/cm; percent secondary sperm abnormalities, .92 %/cm; percent normal sperm, 1.28 %/cm; total breeding soundness examination score, .28 units/cm and scrotal circumference, .306 cm/cm. A heritability of .39 was obtained for scrotal circumference. PMID- 2592278 TI - Estimation of genetic parameters among breeding soundness examination components and growth traits in yearling bulls. AB - Data on breeding soundness examinations (BSE) and performance traits were obtained on 549 yearling beef bulls at the San Juan Basin Research Center, Hesperus, Co from 1976 to 1984. Genetic parameters estimated for components of BSE included percent motility (PMOT), percent primary abnormalities (PPRIM), percent secondary abnormalities (PSEC), percent normal sperm (PNOR), scrotal circumference (SC) and BSE score (BSESC). Performance traits included birth weight, weaning weight, yearling weight and average daily gain. The least squares model included birth year, age of dam and breed as fixed effects, sire/breed as a random variable, and age and percent inbreeding as covariates. Paternal half-sib estimates of heritability were PMOT, .08 +/- .07; PPRIM, .31 +/- .09; PSEC, .02 +/- .05; PNOR, .07 +/- .06; BSESC, .10 +/- .06 and SC, .40 +/- .09. Phenotypic correlations among BSE components and growth traits were generally favorable. Genetic correlations involving percent secondary abnormalities were highly variable with large standard errors. Seminal traits improved as age increased and became poorer as inbreeding increased. PMID- 2592277 TI - Estimation of genetic parameters among reproductive and growth traits in yearling heifers. AB - Growth and reproductive data were obtained on 779 beef heifers at the San Juan Basin Research Center, Hesperus, Co. Genetic parameters were estimated for age of puberty (AOP), age of first calving (AOC), julian day of first calving (DOC), julian day of second calving (DOSC), birth weight, weaning weight, yearling weight, and average daily gain from weaning to yearling and to cycling weights. The least squares model included birth year, age of dam and breed as fixed effects, sire/breed as a random variable, and day of birth and percent inbreeding as covariates. Day of birth was not included in the analyses of AOC, DOC or DOSC. Paternal half-sib estimates of heritability were: AOP, .10 +/- .17; AOC, .01 +/- .12; DOC, .09 +/- .13 and DOSC, .36 +/- .18. Genetic and phenotypic correlations were generally favorable, but genetic correlations were variable with large standard errors. Inbreeding had a detrimental effect on reproductive traits, and a seasonal effect was present for AOP. PMID- 2592279 TI - Influence of single or multiple sires and serving capacity on mating behavior of beef bulls. AB - A study was conducted to determine the effect of serving capacity (SC) on sexual behavior of yearling bulls during single- and double-sire pasture matings. Approximately 60 crossbred virgin bulls were subjected to 3 SC tests, and 20 bulls were selected that were similar in age, BW, testes size and semen quality. Ten bulls were high SC (greater than or equal to 3 services/test) and 10 bulls were low SC (less than or equal to 2 services/test). Competitive order among the 20 bulls also was determined. Single-sire tests were conducted with 15 intact estrual heifers and 1 bull in a pasture for 6 h. Double-sire tests were conducted with 30 estrus-induced, ovariectomized heifers and 1 high SC and 1 low SC bull of approximately equal competitive order for 6 h. Bulls in double-sire tests had more (P less than .007) mounts than those in single-sire tests. High SC bulls in double-sire tests served more heifers (P less than .04) and had more services (P less than .04) than any other SC group and test type. There was no difference (P greater than .10) in the number of mounts or services between high and low SC bulls in single-sire tests. High SC bulls had a greater (P less than .002) percentage of mounts that culminated in a service that did low SC bulls. Conception rate was not different (P greater than .10) between SC groups in single-sire tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592280 TI - Acute changes in blood flow in pigs infused with beta-adrenergic agonists. AB - Previous results indicate that clenbuterol decreases carcass adipose tissue accretion when administered to pigs but does not appear to stimulate the adipose tissue beta-adrenergic receptor. Clenbuterol increases plasma free fatty acid concentration when acutely infused in vivo, suggesting an indirect affect. One possible indirect effect is that clenbuterol could change blood flow to adipose tissue. Blood flow was measured with radiolabeled microspheres in tissues from pigs before and after infusion of a beta-adrenergic agonist for 30 min. High probability levels (up to P less than .2) were used to indicate trends due to extreme variability. Infusion of isoproterenol increased heart rate, plasma free fatty acid concentration and blood flow at many adipose tissue sites and at a few skeletal muscle sites. Infusion of isoproterenol decreased blood pressure. Infusion of clenbuterol increased heart rate and tended to increase blood flow to several skin and adipose tissue sites slightly. The results suggest that increased adipose tissue blood flow may contribute to the accelerated release of free fatty acids when clenbuterol is infused acutely in vivo. PMID- 2592281 TI - Influence of age and testosterone levels on masculine development in rams. AB - Fifty wethers and 51 spring-born rams were divided into five groups and slaughtered at different seasons of the year at average ages of 271, 361, 459, 557 or 652 d to determine the age and season at which differences in secondary sex characteristics could be detected. Serum testosterone concentrations and testes weights were low in January when the rams were 271 d of age and again in April at 361 d of age. By July, at 459 d of age, testosterone concentrations and testes weights had peaked and then decreased the following November at 557 d and February at 652 d. In contrast with plasma testosterone concentrations and testes weights, buckiness scores, splenius to semimembranosus or semitendinosus muscle ratios, splenius muscle weights and neck and shoulder percentages were not seasonal. All of these measures increased significantly up to July and continued to increase slowly, but not significantly, thereafter. Muscle color and texture scores and rib eye color scores tended to increase in a linear manner for both rams and wethers as age increased. Subcutaneous fat from rams was yellower and softer than that from wethers over all age groups. Ram fat firmness did not change (P greater than .05) with age, and the only significant change in ram fat color was between the groups at 271 and 361 d of age. Overall, season of year coupled with higher levels of serum testosterone was related to initial development of secondary sex characteristics in ram lambs. PMID- 2592282 TI - Carcass, muscle and meat characteristics of lean and obese pigs. AB - Six pigs obtained from a lean selected strain and six pigs obtained from an obese selected strain were slaughtered at about 110 kg live-animal weight. Carcasses were evaluated; hams were dissected into bone, skin, fat and lean, and loin samples were obtained for fiber type characteristics, percentage of fat and moisture, collagen analysis, sensory characteristics, textural properties and objective color analysis. Carcasses from lean pigs were longer, had less backfat and larger longissimus muscle cross-sectional areas than carcasses obtained from obese pigs. Hams from lean pigs had less fat, more bone and more lean than hams from carcasses of obese pigs. The percentages and cross-sectional areas of red and white muscle fibers of the longissimus muscle from lean and obese pigs were not different. However, lean pigs had intermediate fibers that were only 79% as large (P less than .10) as intermediate muscle fibers from obese pigs. Intermediate fibers represented only 7 and 10% of total fiber area, whereas white fibers represented 84 and 79% of total fiber area in longissimus muscle of lean and obese pigs, respectively. Overall, lean pigs tended to possess fewer fibers ( 16%) per unit of area than obese pigs, indicating that total muscle fiber hypertrophy was partially responsible for the increased longissimus muscle area of the lean strain. Sensory properties of longissimus meat samples from lean and obese strains were not different. However, the shear force requirement of the longissimus samples from the lean strain were slightly, but significantly (P less than .10), higher than those from the obese strain. No differences were observed in meat color. PMID- 2592283 TI - Effects of source and level of copper on performance and liver copper stores in weanling pigs. AB - Five 28- to 33-d experiments involving 460 crossbred pigs weaned at 28 +/- 2 d of age (initial weight, 6.7 to 8.1 kg) were conducted to determine the effects of feeding high dietary levels of Cu sulfate (CuSO4) or Cu oxide (CuO) on rate and efficiency of gain and liver Cu stores of weanling pigs. The pigs were housed in groups of five to six/pen and fed a fortified, unmedicated, corn-soybean meal dried whey basal diet (1.1% lysine, 30 ppm Cu). In Exp. 1 and 2, pigs (eight replicates) were fed the basal or the basal plus 125 or 250 ppm Cu from CuSO4 or CuO for 28 d. In Exp. 3 and 4, four replications were fed the same diets as in Exp. 1 and 2 plus two additional diets (500 ppm Cu from CuSO4 or CuO). In Exp. 5, dietary levels of 0, 125, 250, 375 or 500 ppm Cu from CuSO4 were evaluated using four replications. At the end of each experiment, the liver from one pig in each pen was collected for Cu analysis. Overall, rate and efficiency of gain were improved (P less than .01) by feeding 125 or 250 ppm Cu as CuSO4, with the 125 ppm dietary level being about 75% as effective in stimulating growth as 250 ppm. Performance of pigs was not different from controls when the highest (500 ppm) level of Cu (from CuSO4) was fed. Liver Cu increased 10- to 70-fold when 250 to 550 ppm Cu from CuSO4 was included in the feed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592284 TI - Forage intake by lactating beef cows differing in potential for milk production. AB - Two feeding trials (early and late lactation) were conducted to measure ad libitum forage intake by beef cows from three breed groups of similar mature weight, but with different milk production potential. Twenty-four cow-calf units, eight from each milk production level (low, medium and high) were grouped (two/pen) based on similarity of cow weight and previous weigh-suckle-weigh and calf weaning weight data. Each pair of cow-calf units was confined to separate pens and allowed ad libitum access to chopped native Sandhills meadow hay. Dry matter intake, cow and calf BW and calf milk consumption were determined. Daily DMI (kg/hd) and milk consumption showed a positive linear response (P less than .05) among low, medium and high milk-producing cows. When cow DMI was expressed as g/unit mean cow BW during the trial, both a positive linear (P less than .05) and a quadratic response (P less than .01) expressed the relationship among production levels during early and late lactation. Calf forage intake, birth weight and adjusted 181- and 205-d weaning weight had no linear or quadratic relationship (P greater than .10) to milk production levels. However, June 1 calf weight, actual calf weaning weight and calf rate of gain (birth to weaning) had a positive linear (P less than .07) relationship. Best fit regression models with DMI as the dependent variable were developed for each trial based on R2 and CV values of the potential models. The best fit model (R2 = .94, SE = .33) for early lactation included production level as a class variable with cow BW.75 and calf birth weight as independent variables. The best fit model (R2 = .92, SE = .53) for late lactation included actual weaning weight in addition to the variables used during early lactation. PMID- 2592285 TI - Nutritive value of a vegetable amaranth cultivar for growing lambs. AB - Current interest in amaranth as a food resource for humans and animals has been stimulated by activities in germplasm collection and testing in the U.S. Fifteen growing, intact male lambs weighing 18.7 kg were assigned randomly to three diets (five lambs/diet) for a 14-d growth trial followed immediately by an 8-d (4-d adjustment, 4-d collection) digestion and N balance trial to determine the utilization of the forage component (leaves and stems) of an African cultivar (Zimbabwe cultivar PI 482049, Amaranthus cruentus L.) All diets contained 40.95% ground corn, 8.0% soybean meal and 1.05% mineral-vitamin supplement plus either 50% ground alfalfa hay, 25% ground alfalfa hay plus 25% ground amaranth forage or 50% ground amaranth forage. Lambs had ad libitum access to feed during the growth trial and at 4% of BW daily during the digestion and N balance period. Replacement of half or all the alfalfa in the diet with amaranth had no effect on weight gain or feed utilization. Apparent digestibility of cell contents, NDF, ADF, cellulose, ADL, N and GE and percentage of absorbed N retained did not differ among the three diets. The amaranth vegetable cultivar Zimbabwe PI 482049 promoted weight gain and feed utilization equal to that obtained with alfalfa as the sole forage for growing lambs. Additional research is needed to evaluate further the potential role of forage/vegetable amaranth as an animal feed resource. PMID- 2592286 TI - Influence of soybean meal and sorghum grain supplementation on intake, digesta kinetics, ruminal fermentation, site and extent of digestion and microbial protein synthesis in beef steers grazing blue grama rangeland. AB - Six beef steers (British x Brahman) cannulated at the rumen, duodenum and ileum (avg wt 334 kg) and three mature steers (British x British) cannulated at the esophagus were used in a replicated 3 x 3 latin square design and fed no supplement (C), .5 kg soybean meal (SBM) or .5 kg steam-flaked sorghum grain (SFS).head-1.d-1 (DM basis) while grazing blue grama rangeland. Periods of the latin square included a minimum of 14 d for adaptation and 11 d for esophageal masticate collection and digesta sampling. In September, October and November, respectively, forage collected by esophageally cannulated steers averaged 74.5, 88.8 and 71.0% grasses; 2.06, 1.53 and 1.77% N and 68.3, (P greater than .10) by treatment, but total N intake was greater (P less than .05) for SBM vs C and SFS treatments. No differences (P greater than .10) were detected among treatments in OM, NDF, ADF and N digestibilities in the rumen, small intestine or hindgut, but total tract OM digestibility was greater (P less than .10) for SBM and SFS than for C, and total tract N digestibility was greater (P less than .10) for SBM than for C or SFS. Duodenal ammonia N flow was greater (P less than .05) when SBM was fed that when SFS and C were fed, but microbial N and non-ammonia, non-microbial N flows and microbial efficiency were not altered by treatment. Likewise, ileal N flow was not affected (P greater than .10) by treatment. Particulate passage rate, gastrointestinal mean retention time, forage in vitro OM disappearance and in situ rate of forage NDF digestion also were not affected (P greater than .10) by treatments. Ruminal fluid volume was greater (P less than .05) for SFS vs SBM and C treatments, but no differences were noted in fluid dilution rate. Ruminal fluid ammonia concentration was greater (P less than .05) when SBM was fed than when SFS and C were fed (13.5, 9.9 and 8.7 mg/dl, respectively), whereas pH and total VFA concentrations were not different (P greater than .10). Proportion of acetate in ruminal fluid was less (P less than .10) for SBM and SFS than for C. Small amounts of supplemental SBM and SFS had little effect on forage intake, ruminal fermentation and site of digestion but both increased total tract OM digestion in steers grazing blue grama rangeland. PMID- 2592287 TI - Evaluation of production and reproduction of sheep, goat and alpaca genotypes in the Small Ruminant Collaborative Research Support Program. AB - Research has been conducted as part of the Small Ruminant Collaborative Research Support Program (SR-CRSP) on evaluation of genetic resources and methods of effecting genetic improvement of small ruminants in the participating countries. In Kenya, the focus has been on development of a dual-purpose goat for milk and meat production in farming areas, utilizing two locally adapted breeds, Galla and East African, and two imported dairy breeds, Anglo-Nubian and Toggenburg, into a single stock. That research now has reached the stage of field testing. In Morocco, the performance of a highly prolific breed of sheep, the D'Man, and of a less prolific but larger breed, commonly raised under extensive management, the Sardi, and of their F1, F2 and backcross progeny has been evaluated for several reproduction and growth traits. Prolificacy of the D'Man was transmitted additively, but there was favorable heterosis for age at puberty, fertility and growth rate, resulting in substantial heterosis in total performance. In Indonesia, a high degree of variability in prolificacy in sheep appears to be due to segregation of a gene with large effect on ovulation rate, similar in some respects to the Booroola gene. In Peru, work has involved evaluation of effectiveness of current selection programs and estimation of phenotypic and genetic parameters, in unimproved and improved types of sheep, with a limited amount of work also on alpacas. Fiber production is the principal economic trait in alpacas. There also has been work on evaluation of hair sheep in Brazil, Kenya and Indonesia. PMID- 2592289 TI - A predictive model for combined temperature and water activity on microbial growth during the growth phase. AB - An empirical and generalized model is presented, based on a modified Arrhenius equation, for predicting the combined effect of temperature and water activity on the growth rate of bacteria. When it was applied to seven separate sets of wide ranging published results, spanning some 50 years and including a spore-former and a silage micro-organism, predictions explained between 92.9 and 99.0% of the variation in the results with an overall mean of 96.6%. Advantages over existing models are that it is relatively easy to fit to data using least squares regression and requires only five coefficients. These, together with its simplicity and demonstrated wide application, will facilitate its practical use. PMID- 2592288 TI - Partial purification of a serum fraction from fasted pigs that inhibits proliferation of cultured myogenic cells. AB - Sera from pigs fasted as little as 24 h appears to contain a factor(s) that inhibits proliferation of myogenic cells in culture. An inhibitor of myogenic cell proliferation has been partially purified from this sera by using a combination of gel filtration and immunoaffinity chromatography. The inhibitory activity elutes from a Sephacryl S-300 column at a Kav (elution minus void volume divided by total minus void column volume) between .41 and .59. Proteins banding at 76 and 67 kilodaltons appear to predominate on sodium dodecyl sulfate polyacrylamide gels of this fraction. Small quantities of each of these proteins were electrophoretically purified and used to elicit production of anti-76 and anti-67 immunoglobulin G in rabbits. These antibodies were used to prepare anti 76 and anti-67 column was particularly useful in isolating the inhibitor because it removed mitogens that made detection of the inhibitory activity difficult. The partially purified inhibitor inhibits proliferation of L6 myogenic cells in a concentration-dependent manner. On sodium dodecyl sulfate polyacrylamide gels, the predominant proteins in the inhibitor fraction band at approximately 63 and 61 kilodaltons. Inhibitors of myogenic cell proliferation may play an important role in balancing the effects of positive growth factors. PMID- 2592290 TI - In vitro studies of haemolysis by some staphylococci grown in chemically defined media. AB - Staphylococcus aureus (five strains) and Staph. epidermidis (one strain) have been evaluated for comparative growth and haemolysin titre in both brain heart infusion (BHI) and in developed, nutritionally adequate, chemically defined media (CDMs) varying only in amino acid composition. The ability to show a particular haemolytic profile was strain-dependent and the haemolytic titre (HU50/ml) was both strain- and medium-dependent. Highest titres of both alpha and beta type haemolysins were obtained in BHI. Maximum titres were in general detected in the late exponential phase in both CDMs and BHI. Titres declined during the stationary phase in CDMs. Staphylococcus epidermidis produced a delta-type haemolysis profile on BHI-based blood agars, but only rabbit blood was sensitive in agars based on a developed, chemically defined medium (CDM/A; 13 amino acids) in which all six staphylococci grew. The addition of yeast extract to CDM/A increased alpha haemolysin titre, but suppressed beta haemolysin formation; beta haemolysin was, however, detected in yeast extract/phosphate-buffered saline. Strain Wood 46 degraded haemoglobin, but only in (initially) whole blood; red blood cell-free haemoglobin-rich plates (BHI) were unaffected during growth. A novel haemolytic profile is described for Staph. aureus NCTC 8532 growing on blood agars based on CDM/A and may relate to the production of methaemoglobin during haemolysis. PMID- 2592291 TI - Heat resistance of Campylobacter and Yersinia strains by three methods. AB - Two methods of determining the heat resistance of bacteria, a glass cup and a test tube method, were compared with a method using capillary tubes. Three strains of Yersinia enterocolitica, one of Campylobacter jejuni and two of C. coli were tested in physiological saline. The differences between the results obtained by the glass cup method and the reference method were not statistically significant for five strains and were small also for the other, a Yersinia strain. D values obtained by the glass cup method at 58, 60 and 62 degrees C were 1.4-1.8, 0.40-0.51 and 0.15-0.19 min (zeta values 4.00-4.52 degrees C) for the Yersinia strains, and 0.42, 0.13 and 0.07 min (zeta value 5.07 degrees C) for one C. coli strain. For the other Campylobacter strains, D values of 0.71-0.78, 0.24 0.28 and 0.12-0.14 min (zeta values 4.94 and 5.60 degrees C) were recorded at 56, 58 and 60 degrees C. D values obtained at 60 degrees C by the test tube method were 2.7-5.0 min and were considered to be unrealistic. PMID- 2592292 TI - The taxonomic relationship of certain environmental flavobacteria to the genus Weeksella. AB - Forty environmental strains and reference cultures of Flavobacterium, Cytophaga and Weeksella spp. were examined by numerical taxonomy. Twenty-seven strains were recovered in four phena. Phena 1A and 1B comprised 48% of the strains and were sufficiently similar to the genus Weeksella as to suggest possible inclusion in this genus. They could not be accommodated in the existing species W. virosa and W. zoohelcum. Strains from phenon 2 appear to belong neither in the Flavobacterium or the Weeksella genus. Although no reference strains were included in phena 3 and 4 they appear phenotypically to be most similar to F. breve and F. odoratum respectively. PMID- 2592293 TI - Germinal centers in the bone marrow. AB - Germinal centers (GCs) in the marrow have been described, but not systematically studied. Twelve cases from the axial skeleton from patients aged 29-80 years were examined. The male female ratio was 1:5, and the yearly incidence was 0.8% of bone marrow specimens. Most patients were anemic (mean hematocrit 34%); five had eosinophilia. When both clots and core biopsies were obtained, GCs were found more often in clots. Associated lymphoid aggregates were evident in 60% but no patient fulfilled criteria for nodular lymphoid hyperplasia. GCs coexisted in one case with malignant lymphoma. Polyclonal plasmacytosis was present in 40% of the cases. Scattered T cells, ringing the GC, were identified in most cases. S-100 staining demonstrated a peripheral nerve associated with one GC. Marrow GCs have been considered a reaction to splenectomy and a forerunner of malignant lymphoma; neither theory is supported in these cases. The findings raise the possibility of immune function by the marrow in adults, possibly akin to follicular hyperplasia in the spleen. PMID- 2592294 TI - Effect of retinoids on growth factor-induced anchorage independent growth of human fibroblasts. AB - We have studied the effects of all-trans retinol, all-trans retinoic acid, and anhydroretinol, a biologically inactive retinoid, on anchorage-independent growth of human fibroblasts induced by purified growth factors. The anchorage independence assay was conducted in medium supplemented with serum that had had its peptide growth factors inactivated by treatment with dithiothreitol and iodoacetamide. Physiologic concentrations of either all-trans retinol (0.5 microM) or all-trans retinoic acid (1.0 nM) but not anhydroretinol (0.5 microM) reduced the frequency of anchorage-independent growth of normal human fibroblasts induced by platelet-derived growth factor (PDGF). All-trans retinol was also tested for its effect on the frequency of anchorage-independent growth induced by basic fibroblast growth factor (bFGF) and was found to decrease this growth. All trans retinol also reduced the frequency of anchorage-independent growth of the human fibrosarcoma-derived cell line, HT1080, which grew in semisolid medium without added growth factors. Inasmuch as these retinoids reduced the frequency of anchorage-independent growth induced by either PDGF or bFGF and because PDGF and bFGF bind to independent cell membrane receptors and are known to stimulate different pathways leading to DNA synthesis, the data suggest that physiologically active retinoids have an effect on a step that is common to both signal pathways. PMID- 2592295 TI - Development and characterization of primary cultures of smooth muscle cells from the fibromuscular stroma of the guinea pig prostate. AB - Primary cultures of smooth muscle cells (SMCs) were obtained by a two-step enzymatic digestion of guinea pig prostatic stroma. Ultrastructural morphology and growth characteristics of these cells conformed to those reported for SMCs isolated from vascular and visceral tissue sources. Electron microscopic examination indicated that the cells assumed modified myofibroblastoid features in culture. Microfilaments with associated dense bodies were markedly depleted in cultured smooth muscle cells, in comparison with those of the parent tissue. Cultured cells also possessed increased content of rough endoplasmic reticulum indicating the increased secretory or protein-synthetic capacity of the cells. Immunoperoxidase staining for cytoskeletal markers using monoclonal antibodies to desmin and vimentin supported the ultrastructural observations, suggesting a decline in desmin-staining intermediate filaments during "modulation" to the myofibroblastoid form. Despite this depletion of smooth muscle-specific differentiation markers and reversion to more general mesenchymal properties, the cells retained the ability to contract on challenge with norepinephrine, and grew in the characteristic "hill and valley" pattern on attaining confluence. Inasmuch as the estrogen and androgen receptor expression of the parent stromal tissue is also retained, these primary cell cultures should provide a useful model to study regulation of prostatic development. PMID- 2592297 TI - In vitro toxicity of solubilized 2,3,4-trimethylpentane. I. Cytotoxicity and metabolism of TMP using primary hepatocytes. AB - Primary rat hepatocyte suspension cultures (approximately 2 X 10(6) cells) exposed to solubilized 2,3,4-trimethylpentane at concentrations ranging from 7.9 to 31.5 mM under two different culture conditions resulted in a linear dose response, as determined by lactate dehydrogenase leakage and viability data. A significant increase in the 2,3,4-trimethylpentane effective concentration 50 for primary hepatocytes occurred when exposures were implemented in medium containing 0.05% albumin. The effective concentration 50 for hepatocytes exposed to 2,3,4 trimethylpentane in medium lacking and containing albumin were 17.1 and 20.7 mM, respectively. Metabolite analysis by gas chromatography-mass spectrometry of supernatant (lacking or containing albumin) and cell extracts from hepatocyte cultures exposed to 2,3,4-trimethylpentane for 4 h indicated the presence of three metabolites: 2,3,4-trimethyl-1-pentanol, 2,3,4-trimethyl-2-pentanol, 2,3,4 trimethyl-2-pentanol, and 2,3,4-trimethyl-1-pentanoic acid. Electron microscopic examination of 2,3,4-trimethylpentane-exposed primary hepatocytes indicated ultrastructural changes which included abnormal condensed chromatin association with the nuclear membrane, swollen mitochondria, increased amounts of cytoplasmic lipid, significant loss of microvilli from the cell surface, increased vacuolation, and increased numbers of peroxisomes. Although these changes were observed under both culture conditions, they were more severe in cultures lacking albumin. This study indicates that primary hepatocyte suspension cultures provide a useful system for rapidly identifying liver metabolites of selected test compounds of interest. PMID- 2592296 TI - Limited cell attachment time as a method to synchronize cells grown in monolayer culture. AB - A novel method of synchronizing monolayer tissue culture cells is described. By limiting the period of attachment of trypsinized cells and the subsequent removal of unattached cells a G1 population of cells is isolated. Evaluation of the degree of synchrony has been carried out by measuring the labeling index and incorporation of [3H]thymidine into DNA. Further conformation of synchrony, as well as a comparison with synchrony by isoleucine deprivation, was obtained by flow cytometry. The expected peak in DNA synthesis rate following limited attachment was observed. This peak becomes more prominent and shifts to earlier times with shorter attachment intervals. The synchronization method described is simple, rapid, yields a substantial number of cells, and is applicable to many cell lines. PMID- 2592298 TI - Contraction of collagen by human fibroblasts and keratinocytes. AB - In the process of wound healing keratinocytes and fibroblasts play an important role, keratinocytes in the re-epithelization process and fibroblasts in the process of wound contraction. We have studied the role of human keratinocytes and fibroblasts in the rearrangement of collagen in a collagen lattice model system. Our results revealed that keratinocytes as well as fibroblasts rearrange the collagen lattice; this occurs in a cell number and collagen concentration dependent manner. The optimal gel contraction is obtained in the presence of keratinocytes on the top of and of fibroblasts in the collagen lattice, the situation most closely approaching the in vivo situation. Between the two types of cells, differences in morphologic behavior were observed: when incorporated into the gel the keratinocytes retained their spherical shape throughout the whole culture period, but fibroblasts became elongated and formed extensions. Our data suggest that not only fibroblasts but also keratinocytes may be involved in the process of wound contraction. PMID- 2592299 TI - Variable responsiveness of rat tracheal epithelial cells to bovine serum albumin in serum-free culture. AB - The colony-forming efficiency of rat tracheal epithelial (RTE) cells was determined in serum-free media containing different types of commercially available bovine serum albumin (BSA): crude fraction V, essentially globulin free, essentially fatty-acid-free, and essentially globulin- and fatty-acid-free BSA. RTE cells exhibited a concentration-dependent increase in colony-forming efficiency in response to crude fraction V BSA. Similar results were obtained using essentially globulin-free BSA. However, deletion of cholera toxin from the medium resulted in a decrease in the colony-forming efficiency for cells plated in high concentrations (greater than 2 mg/ml) of globulin-free, but not one type of fraction V, BSA. Essentially fatty-acid-free or essentially fatty-acid- and globulin-free BSA stimulated RTE cell colony formation at low concentrations (less than 2.5 to 5 mg BSA/ml) but resulted in concentration-dependent decreases in colony-forming efficiency at higher concentrations. The response of cells to these BSAs was not dependent on cholera toxin. Finally, commercially available fraction V BSA prepared by heat shock, dialysis, charcoal treatment, and deionization was stimulatory at low concentrations but inhibitory at high concentrations. These data suggest that impure preparations of BSA can, under different conditions, stimulate or inhibit cell proliferation and that the expression of these activities is affected by the method of BSA preparation, the concentration of BSA used, and, in some cases, by the presence or absence of cholera toxin. PMID- 2592300 TI - Isolation of alveolar epithelial cells from lung tissue obtained at autopsy. AB - Lung alveolar epithelial cells have been studied in a variety of laboratory animal models, and studies of human alveolar epithelial cells are important for comparison to information obtained from animal studies. Autopsy material is a source of human cells for study. Studies of human autopsy material revealed variables that negatively affected the yield of viable cells. For specimens from adults, these included death greater than 12 h before cell isolation, obvious severe lung fibrosis, longstanding metabolic disorders, and lung congestion indicated by weight of the right middle lobe greater than 150 g. Samples from children yielded significant numbers of viable cells up to 18 h after death. For 17 specimens that conformed to the above criteria, approximately 8.5 x 10(6) alveolar cells were obtained per gram of tissue (tissue weights ranged from 30 to 108 g) using a procedure involving instillation of proteases into the airways. The cells could be further fractionated, and 10 to 15% of the mixed cells obtained were type II pneumocytes. Analysis of NADPH cytochrome-c-reductase distribution in subcellular fractions provided evidence that the cells obtained were intact. Phospholipid enzyme activities and synthetic activity were within the ranges previously found in laboratory studies of freshly obtained animal lungs. These results suggest that significant numbers of viable and functional human lung cells, including type II pneumocytes, can be obtained from autopsy material. PMID- 2592301 TI - Initiation and ultrastructure of a reptilian fibroblast cell line obtained from cutaneous fibropapillomas of the green turtle, Chelonia mydas. AB - Two fibroblastic cell lines were established from explants of fibropapillomas of each of two different green turtles (Chelonia mydas). These cells, designated GTFP (Green Turtle Fibropapilloma), were subcultured approximately 30 times at 30 degrees C in Eagle's minimal essential media supplemented with 2 to 10% fetal bovine serum. The ultrastructural morphology of the cultured fibroblasts is described. The cells contained abundant rough endoplasmic reticulum, polyribosomes, and mitochondria; collagen fibrils were visible in the extracellular space. No viruslike particles or evidence of other pathogenic agents could be demonstrated by electron microscopy in any of the cultured cells examined. PMID- 2592303 TI - Progesterone production and release in cultured placental tissue from diabetic and normal rats fed high calcium. PMID- 2592304 TI - Locomotory behavior of fibroblasts in "sail-sheets". AB - The locomotory behavior of fibroblasts in two-dimensional cultures (e.g., on culture dishes, cover slips, etc.) was first reported by Abercrombie's group. This paper describes some of the features of movement of fibroblasts in a unique culture system known as sail-sheet cultures (SSCs). Cells in SSCs grow mostly on one another in a three-dimensional form that resembles, to some extent, the in vivo situation. We grew chicken heart fibroblasts (CHFs) as SSCs and studied their locomotory behavior by time-lapse filming extended for periods ranging from 12 h to several days. It was found that CHFs grown as sail-sheets exhibit many features of movement as observed in conventional two-dimensional cultures (CCs). However, we observed that CHFs in SSCs, like those in vivo, lack leading lamella directing their movement. Furthermore, locomotion is significantly slower in SSCs than in CCs. Based on data on the movement of CHFs within the mesh holes of inert grids, we suggest that the mesenchymal cells in SSCs, in addition to their individual movement, move in sheets and that their movement in sheets results in the closure of the mesh holes, a situation that resembles the phenomenon of healing of wounds. Thus SSCs provide a model system for the study of healing of wounds. The presence of collagenlike extracellular matrix (CLECM) between cellular layers in SSCs suggests that CLECM may be involved in guiding the locomotory behavior of CHFs in SSCs. PMID- 2592302 TI - Optimization of culture conditions for human corneal endothelial cells. AB - Long-term cultivation of human corneal endothelial cells (HCEC) was optimized with respect to different components of the culture system: 25 different nutrient media, different sera, 6 mitogens and various substrates were tested in their ability to influence clonal growth and morphology of HCEC. F99, a 1:1 mixture of the two media M199 and Ham's F12, was the most effective basal medium in promoting clonal growth of HCEC. Among various sera, human serum and fetal bovine serum showed optimal growth promoting activities in combination with F99, whereas newborn bovine serum (NBS) was by far superior for the development of a typically corneal endothelial morphology. Crude fibroblast growth factor (FGF), or alternatively endothelial cell growth supplement, was absolutely essential for clonal growth of HCEC at low serum concentrations, for example 5% NBS. Formation of a monolayer with a morphology similar to corneal endothelium in vivo was observed only on culture dishes coated with basal membrane components such as collagen type IV, laminin, or fibronectin. The most pronounced effect on morphologic appearance was obtained by culturing the cells on the extracellular matrix (ECM) produced by bovine corneal endothelial cells. Moreover, ECM could substitute for crude FGF in clonal growth assays. PMID- 2592305 TI - Effects of different concentrations of serum on cartilage growth in an organ culture system. AB - The purpose of the present study was to examine the effects of various concentrations of serum on the behavior of neonatal condylar cartilage when cultured in an organ culture system. Mandibular condylar cartilages were obtained from newborn ICR mice, of which the zone of undifferentiated chondroprogenitor cells along with a few layers of young cartilage cells were cultivated at the medium-air interface. The incubation medium included fetal bovine serum at concentrations ranging from 0 to 10%, and the explants were kept in vitro up to 10 d. The serum-free medium maintained the chondrogenic expression, and the overall size of the cartilagenous portion of the explants increased with the decrease of the concentrations of serum in the medium. When explants were labeled with [3H]thymidine and were then processed for autoradiography, the peak of labeling was noticed at 48 h, a feature that recapitulated itself in all cultures (73, 140, 175, 201, and 129 labeled cells per chondroprogenitor zone in explants grown in 0, 1, 2.5, 5, and 10%, respectively). It can be concluded that serum free medium maintains the chondrogenic phenotype of condylar cartilage in vitro. PMID- 2592306 TI - Gas chromatographic determination of nicotine in environmental tobacco smoke: collaborative study. AB - A gas chromatographic method for determination of vapor phase nicotine in environmental tobacco smoke (ETS) was collaboratively studied by 6 laboratories. Nicotine is desorbed from XAD-4 sample tubes with ethyl acetate containing triethylamine and determined by gas chromatography with nitrogen-selective detection. Each collaborator received blind duplicate samples at each of 6 nicotine concentrations. Three concentrations were generated by spiking XAD-4 tubes with known amounts of nicotine; the remaining 3 concentrations were ETS samples obtained in a carefully controlled environmental chamber containing sidestream and exhaled mainstream smoke from 1R4F Kentucky reference cigarettes. Repeatability and reproducibility relative standard deviations ranged from 4.4 to 11.1% and from 7.0 to 11.1%, respectively, for nicotine concentrations evaluated (up to 6 micrograms/cu m). The method has been adopted official first action. PMID- 2592307 TI - Effect of gelatin on recovery of hair fragments in filth analysis. AB - Prior literature has recommended the use of gelatin capsules or gelatin film for transferring spike elements to samples being examined for recovery studies. It was believed that gelatin had no effect on the recovery of filth spike elements. However, this study shows that hair recovery is lower when gelatin is present in direct trap-off procedures. Two types of gelatin capsules, gelatin film, and strips of filter paper were used to transfer spike filth elements. A comparison study employing an acid digestion and wet sieving procedure was also performed and showed that gelatin had little or no effect on the recovery of hairs using this type of procedure. An additional test was performed using gelatin added to water containing the same type of spiked filth elements. No hair fragments were recovered but all insect fragments were recovered. All recovery studies were performed using only water in the liquid phase of the trap flask extractions, with mineral oil or heptane as the flotation medium. No food product was used. PMID- 2592308 TI - Ethyl carbamate levels in selected fermented foods and beverages. AB - Ethyl carbamate (EC), also known as urethane, is an animal carcinogen and a by product of fermentation. Because EC has been found in distilled spirits and wines, a variety of fermented foods and beverages were analyzed to assess its occurrence in other products. Previously described methods using a gas chromatograph-thermal energy analyzer with a nitrogen converter were modified for each matrix and gave recoveries of greater than 80%, with a limit of detection in the 1-2 micrograms/kg (ppb) range. A total of 152 test samples were analyzed; EC levels ranged from none found to 3 ppb in 15 cheeses, 6 teas, 12 yogurts, and 8 ciders; from none found to 13 ppb in 30 breads and 69 malt beverages; and from none found to 84 ppb in 12 soy sauces. Gas chromatography/mass spectrometry/mass spectrometry was used to confirm EC identity and to quantitate EC in selected food extracts. PMID- 2592309 TI - Spectrophotometric determination of some benzene sulfonamides with 7,7,8,8 tetracyanoquinodimethane. AB - A new spectrophotometric method for the determination of some unsubstituted benzene sulfonamides is presented. The method is based on the interaction of these derivatives with 7,7,8,8-tetracyanoquinodimethane at pH 9.0-9.5 to produce intense blue products. The quantitation of the products was carried out at 578 nm. Beer's law was obeyed over a wide range of concentrations for all sulfonamide compounds studied. Optimum analytical conditions were determined, and the color produced was stable for at least 90 min at 25 degrees C. Analytical data for determination of sulfonamide compounds in pure form are presented together with application of the proposed method for analysis of some commercially available pharmaceutical preparations. The results are in good agreement with those obtained by official procedures. PMID- 2592310 TI - Formaldehyde quantitation in air samples by thiazolidine derivatization: factors affecting analysis. AB - A new method for the determination of trace levels of formaldehyde in air was developed and validated. The method is based on the reaction of formaldehyde with cysteamine to form thiazolidine. Air samples containing trace levels of formaldehyde were prepared from paraformaldehyde. The percent yield of formaldehyde from paraformaldehyde was 85.1 +/- 1.14%. Air samples were bubbled into an aqueous cysteamine trap. Thiazolidine formed from formaldehyde and cysteamine in the trap was determined by gas chromatography with a fused silica capillary column and a nitrogen-phosphorus detector (NPD). The lowest detection level for thiazolidine was 17.2 pg, equivalent to 5.80 pg formaldehyde. The recovery efficiency of trace gas phase formaldehyde in air was greater than 90%. Formaldehyde levels in ambient laboratory air were 48.9-56.2 ppb (v/v). PMID- 2592311 TI - Liquid chromatographic determination of sulfite in grapes and selected grape products. AB - A liquid chromatographic (LC) method is described for the determination of sulfite in grapes and certain grape products. Sulfite is extracted from grapes with aqueous formaldehyde solution buffered at pH 5; free sulfite is converted to hydroxymethylsulfonate (HMS), which is extremely stable at pH 3-7. Subsequent heating to 80 degrees C for 30 min converts reversibly bound forms of sulfite to HMS. The extract is then analyzed by reverse-phase ion-pairing liquid chromatography, using a C18 column and a mobile phase of aqueous 0.005 M tetrabutylammonium ion in 0.05 M acetate, pH 4.7, and a flow rate of 1 mL/min. Aqueous KOH is added to the eluate to convert HMS to free sulfite, which is then treated with 5,5'-dithiobis[2-nitrobenzoic acid]. This reaction produces the 3 carboxy-4-nitrothiophenolate anion, which is determined by measurement of electronic absorption at 450 nm. For grapes spiked with HMS at 5-20 ppm (as SO2), recoveries ranged from 92 to 112%, with a coefficient of variation of 4.6%. The method was also used to determine sulfite in various grape products. Results were comparable to those obtained by the AOAC official Monier-Williams method. PMID- 2592312 TI - Honey protein as internal standard for stable carbon isotope ratio detection of adulteration of honey. AB - Using the difference in stable carbon isotope ratio between a honey and its protein fraction permits objective evaluation of possible adulteration of honey with small amounts (7-20%) as well as larger amounts of corn or cane sugar. The present uncertainty in interpretation of results from pure honey with delta 13C values outside the generally accepted limits for pure honey of -27.5% to -23.5% is eliminated; likewise TLC testing to resolve questionable samples with delta 13C values between -23.5 and -21.5% is not needed. Fifty certified samples of pure honey were used to establish criteria for purity, and 38 other samples with delta 13C values in the "questionable" or "adulterated" range for the AOAC official method were tested. A difference of 1.0% or more between honey and protein fractions is proposed to indicate adulteration. PMID- 2592313 TI - Precolumn phenylisothiocyanate derivatization and liquid chromatography of amino acids in food. AB - A precolumn phenylisothiocyanate derivatization method is described for the determination of amino acids in protein hydrolysates from a wide variety of complex food matrixes, with and without performic acid oxidation pretreatment. Analysis of samples that were not pretreated with performic acid was necessary since this pretreatment destroyed an average of 25% of the histidine and 87% of the tyrosine present in the food samples. This method is rapid and reproducible; coefficients of variation between duplicate analyses of the same food item were less than 5% for a majority of the amino acids. Occasionally, variation between duplicate analyses for histidine and tyrosine was greater than 10%. Recoveries of amino acids added to samples were in the 100% range. PMID- 2592314 TI - Detection of pork and lard as adulterants in processed meat: liquid chromatographic analysis of derivatized triglycerides. AB - A new method is described for detection of pork and lard as adulterants in processed beef and mutton mixtures. The unsaturated triglycerides in the fat are ozonized and then derivatized. The mixture of derivatized and saturated triglycerides is analyzed by liquid chromatography using a reverse-phase column and a UV detector. Pork fat has larger amounts of triglyceride containing saturated fatty acid at the C-2 position than does the fat of other meat. The ratio of triglyceride containing saturated fatty acid vs triglyceride containing unsaturated fatty acid at the same (C-2) position (SSU/SUS) in a sample is compared with those of pure meats. The presence of pork in the sample causes the ratio to increase compared with ratios for pure beef or mutton. The increase in the SSU/SUS ratio is significant for the addition of 1% pork in beef. In the case of mutton, the addition of 3% pork causes a noticeable change. The method is reliable and is also applicable to samples containing only fat. Processing (heating or cooking) does not affect the ratios. PMID- 2592315 TI - Liquid chromatographic-atomic absorption spectrophotometric method for determination of methyl mercury in seafood: collaborative study. AB - A previously developed method that uses a simplified sample preparation procedure and atomic absorption detection of liquid chromatographic eluates for the determination of methyl mercury in seafood has been collaboratively studied. The unique feature of the method involves the use of a specially designed interface for the generation of mercury vapor. Methyl mercury is isolated from the blended sample by chloroform elution from a diatomaceous earth-hydrochloric acid column. The organomercury compound is then extracted into a small volume of 0.01M sodium thiosulfate solution. An aliquot of this solution is injected onto a Zorbax ODS column and eluted with methanol-ammonium acetate solution (3 + 2), pH 5.7, containing 0.01% mercaptoethanol. Mercury is detected by flameless atomic absorption spectrophotometry using the interface. The samples analyzed in the study were unspiked swordfish, unspiked and spiked lobster, and unspiked and spiked tuna. The spiked samples contained methyl mercury both above and below the U.S. Food and Drug Administration guideline level of 1 microgram Hg/g. Reproducibility relative standard deviations ranged from 10.5% at 1 microgram Hg/g to 18.2% at about 0.1 microgram Hg/g. Accuracy, measured by comparison to reference values obtained by the Associate Referee, ranged from 94.4 to 99.6%. The method has been adopted official first action. PMID- 2592316 TI - Reliability of repeatability and reproducibility measures in collaborative trials. AB - The acceptability of a new analytical method is generally assessed in terms of repeatability and reproducibility estimates derived from a collaborative study. Procedures are presented for calculating confidence intervals and operating characteristic curves for acceptance criteria based on the repeatability and reproducibility estimates. Comparisons of the reliability of estimates are provided for various numbers of collaborators. With a small number of collaborators, the estimates of reproducibility are not reliable and decisions regarding acceptability of a method will be heavily based on the method's repeatability rather than the property of most interest, namely, the reproducibility of the method. PMID- 2592317 TI - Comparison of two ELISA screening tests with liquid chromatography for determination of aflatoxins in raw peanuts. AB - A study was conducted to evaluate the performance of 2 enzyme-linked immunosorbent assays (ELISA) for rapidly screening samples of peanuts for the presence of aflatoxin. The EZ-Screen Quick Card Test and the Afla-10 Cup Test were compared with liquid chromatography in duplicate analyses of common extracts of peanuts contaminated in the range of 0-70 ppb (ng/g). Each assay properly identified 95% of samples containing no detectable aflatoxin as negative and greater than 97% of samples containing greater than 10 ppb aflatoxin as positive. The card test, which had a 20 ppb detection threshold, identified as positive 32 of 34 samples in the 11-20 ppb range. This indicates that the card test might actually have a detection threshold closer to 10 ppb. Most of the errors associated with the assays occurred on samples containing less than 10 ppb aflatoxin. The cup and card tests identified 76 and 67% of the samples, respectively, as negative, in the range of 4-10 ppb. For samples either negative or contaminated above their detection thresholds for the assays, the methods are well suited for use as rapid screening tests. PMID- 2592318 TI - Determination of aflatoxin concentrations in peanut butter by enzyme-linked immunosorbent assay (ELISA): study of three commercial ELISA kits. AB - Sixteen United Kingdom analytical laboratories participated in an evaluation of 3 commercially available enzyme-linked immunosorbent assay (ELISA) kits for analysis of aflatoxin in peanut butter. Each laboratory was sent 3 sets of 10 randomly numbered samples of peanut butter. Each set consisted of 5 pairs of undisclosed duplicates. Four of the sets of duplicates were naturally contaminated butters with "target" aflatoxin values (estimated by liquid chromatography) between 8 and 81 micrograms/kg. The fifth pair was a blank peanut butter containing approximately 3 micrograms/kg of total aflatoxins. A statistical treatment of the results of the study is presented, together with discussion of the relative merits of the different kits. PMID- 2592319 TI - Determination of linuron in potatoes using capillary column gas chromatography/mass spectrometry. AB - A convenient method for the determination of the N-methyl,N-methoxy-phenylurea herbicide (linuron) in potatoes has been developed. The herbicide is extracted from potatoes using a slightly modified Luke multiresidue procedure. The extract is analyzed directly by gas chromatography with cold on-column injection, using an ion trap mass spectrometer in the chemical ionization mode as the detector. Quantitation is performed using p-bromonitrobenzene as the internal standard. The limit of detection is 0.1 ppm. Recoveries of linuron in potatoes averaged 112 +/- 6% at the 0.5 ppm level, and 110 +/- 2% at the 0.2 ppm level. No linuron residues were found in 25 potato samples that were analyzed by this method. Two other N methyl,N-methoxy-phenylurea herbicides, metobromuron and chlorbromuron, are also sufficiently stable to be determined by this method, but the N,N-dialkyl phenylurea herbicides neburon, diuron, and monuron are too thermally unstable and degrade in the gas chromatograph. PMID- 2592320 TI - Liquid chromatographic-electrochemical determination of ethylenethiourea in foods by revised official method. AB - AOAC official method 29.119-29.125 was revised to determine ethylenethiourea (ETU) directly by a liquid chromatographic-electrochemical (LC-EC) determinative technique and to improve ETU recovery. ETU is extracted from food products with a methanol-aqueous sodium acetate solution. A portion of the concentrated filtrate is added to a column of diatomaceous earth, and ETU is eluted with 2% methanol in methylene chloride to separate it from food coextractives, which are retained on the column. The eluate is collected in a siliconized flask and evaporated, the residue is dissolved in water, and 20 microL of solution is injected onto an LC graphitized carbon column. ETU is eluted from the LC column with a mobile phase of acetonitrile-aqueous 0.1M phosphoric acid-water (5 + 25 + 70), and the eluted ETU is detected by using an amperometric electrochemical detector equipped with a gold/mercury working electrode. Recovery data were obtained by fortifying 13 food products with ETU: baked potatoes; canned applesauce, mushrooms, creamed spinach, green beans, spinach, and tomatoes; cooked fresh cabbage and frozen collards; fresh celery and lettuce; grape jelly; and powdered sugar cake donuts. Raw celery was found to cause low ETU recoveries. Average percent recoveries of ETU from the other 12 food products were 92 with a standard deviation of 12 for the low (0.05 and 0.1 ppm) fortification levels and 90 with a standard deviation of 6 for the higher (0.5 and 1 ppm) fortification levels. The limits of quantitation were 0.01 and 0.02 ppm for food products with low and high sugar content, respectively. PMID- 2592321 TI - Chemical derivatization analysis of phenols. Part VI. Determination of chlorinated phenolics in pulp and paper effluents. AB - Based on the in-situ acetylation procedure, a method for the determination of 31 chlorinated phenols, guaiacols, catechols, syringols, and vanillins in pulp and paper effluent samples has been successfully developed. Except for 4 chlorocatechol, this procedure provided satisfactory recovery for all phenols at 3 levels of fortification, namely, 400, 40, and 4 micrograms/L. The acetyl derivatives were analyzed by gas chromatography using a 30 m DB-5 capillary column interfaced to an electron-capture detector. Mass spectral abundance data for the characteristic ions of the acetyl derivatives were used for confirmation of compound identities. By operating a mass selective detector in the selected ion monitoring mode, this procedure was further extended to the monochlorinated phenolics. Using a 50 mL effluent sample, the method detection limit was 0.5 micrograms/L for all except the monochlorinated compounds, which had a detection limit of 1 microgram/L. Several effluent samples from a Canadian paper mill were analyzed by this procedure and the results are presented. PMID- 2592322 TI - Determination of daminozide in apples by gas chromatography/chemical ionization mass spectrometry. AB - A method using gas chromatography/chemical ionization mass spectrometry (GC/CIMS) for the determination of daminozide residues in apples has been developed. Daminozide was separated from the sample matrix by water extraction and cation exchange, converted to the methyl ester by treatment with HCl-methanol, and determined by GC/CIMS using succinonitrile as an internal standard. The detection level was 0.05 ppm. Recoveries were 92-104% from apples spiked at the 0.05-0.5 ppm levels. Of the 25 apple samples analyzed, only 2 were positive for daminozide (1.04 and 0.32 ppm). PMID- 2592324 TI - Simplified extraction and cleanup for multiresidue determination of pesticides in lanolin. AB - In the proposed method, a light petroleum solution of lanolin (wool fat) is adsorbed on diatomaceous earth in an Extrelut column, and the pesticides are eluted with acetonitrile saturated with light petroleum. After evaporation to a small volume, the extract is subjected to solid-phase extraction (SPE) on a C-18 column. The acetonitrile eluate is evaporated to dryness and the residue is taken up in light petroleum. Organophosphorus pesticides are determined by temperature programmed gas chromatography (GC) on a wide-bore column using a flame photometric detector in the phosphorus mode. Organochlorine pesticides are determined after miniaturized Florisil cleanup by classic GC on an OV-17/QF-1 packed column, using an electron capture detector. This procedure is more rapid and straightforward than the time-consuming AOAC extraction method, 29.014. Cleanup was better and the results obtained were comparable. Recoveries for 13 organochlorine and organophosphorus pesticides, frequently found in lanolin, ranged from 80 to 90%. PMID- 2592323 TI - Confirmation of phorate, terbufos, and their sulfoxides and sulfones in water by capillary gas chromatography/chemical ionization mass spectrometry. AB - A gas chromatographic/mass spectrometric method capable of confirming phorate, terbufos, their sulfoxides, and sulfones in water is reported. Parents and their metabolites are separated in less than 5 min using a short capillary GC column and high carrier gas linear velocities. Positive ion chemical ionization mass spectrometry generates (M + H) ions indicative of the different molecular weights of the analytes and at least one confirmatory fragment ion for each analyte. Residues have been qualitatively confirmed at the 1 ppb level in fortified water samples from a variety of sources. Apparent residues in control water were less than 0.1 ppb. PMID- 2592325 TI - Enzymatic hydrolysis of biological and environmental samples as pretreatment for analysis. AB - Four commercially available proteases were tested, in conjunction with a lipase, for efficacy in hydrolyzing 3 tissue substrates: cod fillet, chicken egg, and bovine liver. Enzymatic hydrolysis of tissues minimizes the formation of emulsions during liquid-liquid extraction and does not accelerate the decomposition of acid- or base-labile analytes. Recovery of hexane and benzene phases from the hydrolysates was also evaluated. Protease from Streptomyces griseus combined with lipase from Candida cylindracea (available commercially) produced the highest percent hydrolysis (relative to classical acid hydrolysis) in all 3 tested tissues (60-95%) and the greatest recovery of hexane (100%) and benzene (92-100%) solvent phases. PMID- 2592326 TI - Multiple myeloma. Analysis of fifty cases. AB - Fifty patients of multiple myeloma have been studied. Seventy eight per cent of the patients were in the 5th, 6th and 7th decades of life. Commonest presenting feature was bone pains (76%). 8%, 20% belonged to stage I, II and III respectively. Skull (58%), ribs (52%) and pelvis (24%) were most commonly involved. Immunoelectrophoresis revealed IgG type of myeloma in 76% and IgA type in 10% cases. Bence-Jones proteinuria was seen in 60% of patients; Kappa specificity was commoner than lambda. Overall survival at 30 months was 50%. The survival was adversely influenced by advanced stage, higher plasma cell count in the bone marrow, low haemoglobin and high serum creatinine values. PMID- 2592327 TI - Retinopathy in insulin dependent diabetes mellitus (IDDM) in south India. AB - The prevalence of diabetic retinopathy was assessed by direct and indirect ophthalmoscopy in a group of patients with insulin dependent diabetes mellitus (IDDM). Fourteen percent of patients had retinopathy. Proliferative retinopathy and severe background retinopathy including maculopathy were both seen in four percent of patients. It is possible that the lower prevalence rates for these complications is due to the shorter duration of diabetes in our patients. PMID- 2592328 TI - Clinical, haemodynamic and echocardiographic study in chronic cor pulmonale. AB - Thirty patients of chronic cor pulmonale were studied clinically and by chest skiagram, electrocardiography, echocardiography, pulmonary function tests, arterial blood gas analysis and, wherever possible by right heart catheterization. Pulmonary arterial pressures (PAP) correlated significantly only with cardiomegaly on skiagram and with arterial oxygen tension (PaO2). There was no significant correlation between mean PA pressures and prominent pulmonary conus on RVH by ECG, FEV1, PaCO2 or right ventricular outflow tract dimensions by echocardiography. Left ventricular function, as assessed by pulmonary capillary wedge pressure on cardiac catheterization, by LV ejection fraction and fractional shortening on echocardiography was normal in all cases except two (6.67%). There was significant increase in left ventricular posterior wall thickness in the patients studied. PMID- 2592329 TI - Posterior fossa abscesses. A review of 33 cases. AB - Thirty three cases of posterior fossa abscesses seen over a period of 20 years are reviewed. 84.8% of these were secondary to otogenic disease. Two abscesses were due to tuberculosis and one due to actinomycotic infection. The overall mortality was 12.1%. Total excision of the abscess with appropriate antibiotic therapy was associated with an operative mortality of 3.4%. PMID- 2592330 TI - Lead-II changes in anterior wall infarction. PMID- 2592331 TI - Unusual presentation of aneurysm of aorta. AB - An unusual case of a saccular aneurysm of arch of aorta, masquerading as pulmonary artery branch stenosis, proved by cardiac catheterisation and angio cardiography is presented. PMID- 2592332 TI - Echinococcic pseudotuberculosis of peritoneum. AB - A rare case of hydatid cyst of liver presenting with ascites masquerading as peritoneal tuberculosis is presented. PMID- 2592333 TI - Balloon mitral valvotomy. A new technique. AB - Balloon mitral valvotomy is a new technique for non-operative treatment of mitral stenosis and is performed by using single or double balloon. The technique is complex, involves transseptal puncture, however, can be safely performed in experienced catheterisation laboratory. The technique has been applied in calcific and noncalcific valves, mitral restenosis and also in presence of atrial fibrillation. The results with double balloon valvotomy at the present time is costlier than closed mitral valvotomy. The technique is promising and large trials are awaited to see its future status. PMID- 2592334 TI - A case of hemiparesis with systolic murmur at left sternal border. PMID- 2592335 TI - Cardiac auscultation. PMID- 2592336 TI - Professor H Zumkley memorial lecture: 1990. PMID- 2592337 TI - Why people instead of patients are hospitalised? PMID- 2592338 TI - Comparative bioavailability of Mazetol and Tegretol. PMID- 2592340 TI - Multiple aneurysms in Marfan's syndrome. PMID- 2592339 TI - Primary gastrointestinal lymphomas. PMID- 2592341 TI - Alcohol and relative polycythemia. PMID- 2592342 TI - A phylogenetic analysis of the mycoplasmas: basis for their classification. AB - Small-subunit rRNA sequences were determined for almost 50 species of mycoplasmas and their walled relatives, providing the basis for a phylogenetic systematic analysis of these organisms. Five groups of mycoplasmas per se were recognized (provisional names are given): the hominis group (which included species such as Mycoplasma hominis, Mycoplasma lipophilum, Mycoplasma pulmonis, and Mycoplasma neurolyticum), the pneumoniae group (which included species such as Mycoplasma pneumoniae and Mycoplasma muris), the spiroplasma group (which included species such as Mycoplasma mycoides, Spiroplasma citri, and Spiroplasma apis), the anaeroplasma group (which encompassed the anaeroplasmas and acholeplasmas), and a group known to contain only the isolated species Asteroleplasma anaerobium. In addition to these five mycoplasma groups, a sixth group of variously named gram positive, walled organisms (which included lactobacilli, clostridia, and other organisms) was also included in the overall phylogenetic unit. In each of these six primary groups, subgroups were readily recognized and defined. Although the phylogenetic units identified by rRNA comparisons are difficult to recognize on the basis of mutually exclusive phenotypic characters alone, phenotypic justification can be given a posteriori for a number of them. PMID- 2592343 TI - Transcription from the P1 promoters of Micromonospora echinospora in the absence of native upstream DNA sequences. AB - We demonstrated previously that the 0.4-kilobase DNA fragment from Micromonospora echinospora contains multiple tandem promoters, P1a, P1b, P1c, and P2, which are also functional when cloned into Streptomyces lividans. We now show by in vitro transcription with Streptomyces RNA polymerase that each of these promoters is an authentic initiation site, rather than a processing site for transcripts which initiate further upstream. The DNA sequence requirements for the closely spaced promoters P1a, P1b, and P1c, which are coordinately induced during stationary phase in M. echinospora, were examined by deletional analysis in S. lividans. The P1a and P1b promoters were functional despite deletion of native sequences 5 and 17 base pairs upstream of each initiation site, respectively. Thus, P1a and P1b had greatly reduced upstream DNA sequence requirements compared with typical procaryotic promoters. In contrast, transcription from promoter P1c was significantly decreased when native sequences 34 base pairs upstream were replaced. PMID- 2592344 TI - xylE functions as an efficient reporter gene in Streptomyces spp.: use for the study of galP1, a catabolite-controlled promoter. AB - We describe the development of a convenient and sensitive reporter gene system for Streptomyces spp. based on the use of a promoterless copy of the xylE gene of Pseudomonas putida. The xylE gene product is a catechol dioxygenase, which converts the colorless substrate catechol to an intensely yellow hydroxymuconic semialdehyde. A promoterless copy of xylE was placed under the transcriptional control of galP1, a glucose-repressed and galactose-induced promoter from Streptomyces lividans, and its expression was examined in bacterial colonies on agar plates or in liquid cultures grown in the presence of glucose or galactose as the sole carbon source. On plates, colonies of bacteria grown on galactose turned bright yellow within a few minutes of being sprayed with a solution of catechol, whereas colonies on glucose-containing plates remained white or only slightly colored, even after extensive incubation. Activity of galP1-xylE fusions was conveniently measured in crude cell extracts with a simple colorimetric assay and was shown to faithfully reflect intracellular RNA levels, as determined by quantitative dot blots. Moreover, differences in expression levels of xylE fusions driven by mutant galP1 promoters were readily apparent in color reactions on plates. The properties of xylE as a reporter gene thus make it suitable not only for quantitatively monitoring expression of regulated promoters in Streptomyces spp. but also for recovering mutations that alter the expression levels of promoters of interest. PMID- 2592345 TI - Cloning of the crystalline cell wall protein gene of Bacillus licheniformis NM 105. AB - A protein with a tetragonal pattern, defined as RS protein, was found on the wall surface of an alkaline phosphatase secretion-deficient mutant (NM 105) of Bacillus licheniformis 749/C. The protein was present on the wall surface of the exponential-growth-phase cells, but at the stationary growth phase it was overproduced and hypersecreted. This protein was precipitated to homogeneity from the culture fluid by 80% ammonium sulfate saturation and chilled acetone. The molecular mass of the protein was 98 kilodaltons, and it had a single subunit in a sodium dodecyl sulfate gel. Specific anti-RS antibody was generated in rabbits and used to immunolabel the RS protein on the cells at different growth phases. In early-exponential-growth-phase cells, the outside surface of the wall, the cytoplasm, and the inside surface of the cytoplasmic membrane were labeled. In stationary-growth-phase cells, the cytoplasm was poorly labeled, but the labeling on the outside surface of the wall was high. AB. licheniformis NM 105 gene library was made by using the lambda phage EMBL3. The RS protein expression from this gene library was detected by a modified autoradiographic procedure. One of the amplified RS protein-positive plaques (4213-1) containing recombinant DNA was chosen, and the restriction map of this DNA was prepared. The RS protein expressed in Escherichia coli NM 539 infected with 4213-1 recombinant phage had a lower molecular mass than the purified authentic RS protein. The 4.5-kilobase pair (kbp) SalI-EcoRI fragment of the recombinant DNA was cloned in the shuttle plasmid pMK4 to construct pMK462, which was expressed in B. subtilis MI112 and produced the RS protein identical in molecular mass to the purified authentic RS protein. The RS protein expression was also demonstrated in cryosections of transformed E. coli and B. subtilis cells by immunoelectron microscopy. The 1.2 kbp SalI-HindIII and 1.8-kbp HindIII-HindIII recombinant DNA restriction enzyme fragments, respectively, from the right of the restriction map produced anti-RS antibody cross-reacting proteins. The expression of the 1.2-kbp SalI-HindIII DNA fragment cloned in pUC8 could be induced with isopropyl-beta-D thiogalactopyranoside. The 1.8-kbp DNA restriction fragment hybridized with both the chromosomal DNA of strain NM 105 and the recombinant phage 4213-1 DNA. The RS gene expression was finally demonstrated in transformed E. coli 539 cells by in situ hybridization of frozen thin sections with the 1.8-kbp HindIII biotin-dATP probe and immunolabeling these with anti-biotin immunoglobulin G and protein A gold. PMID- 2592346 TI - Characterization of a dynamic S layer on Bacillus thuringiensis. AB - The surfaces of three Bacillus thuringiensis strains possess an S layer composed of linear arrays of small particles arranged with p2 symmetry and with a = 8.5 nm, b = 7.2 nm, and gamma = 73 degrees. Platinum shadows of whole cells and S layer fragments revealed the outer surface of the array to be smooth and the inner surface to be corrugated. Treatment with 2 M guanidine hydrochloride at pH 2.5 to 4 best removed the S layer for chemical characterization; it was a relatively hydrophilic 91.4-kilodalton protein with a pI of 5, no detectable carbohydrate, cysteine, methionine or tryptophan, and 21.2% nonpolar residues. No N-terminal homology with other S-layer proteins was evident. Antibody labeling experiments confirmed that the amount of S layer was proportional to the growth phase in broth cultures. Late-exponential- and stationary-growth-phase cells typically sloughed off fragments of S layer, and this may be the result of wall turnover. Indigenous autolytic activity in isolated walls rapidly digested the wall fabric, liberating soluble S-layer protein. At the same time, proteases frequently reduced the molecular weight of the 91.4-kilodalton protein, but these polypeptides could still be identified as S-layer components by immunoblotting. As cultures were serially subcultured, the frequency of appearance of the S layer diminished, and it was eventually lost. The dynamic nature of this S layer makes it atypical of most previously identified S layers and made it unusually difficult to characterize. PMID- 2592347 TI - Binding to collagen by Yersinia enterocolitica and Yersinia pseudotuberculosis: evidence for yopA-mediated and chromosomally encoded mechanisms. AB - Binding of Yersinia enterocolitica and Yersinia pseudotuberculosis strains to type I, II, and IV collagens has been studied. Wild-type strains which harbored the 40- to 50-megadalton virulence plasmid specifically bound all three types of collagen. Curing of the virulence plasmid or Tn5 insertion in the yopA gene encoding the temperature-inducible outer membrane protein YOP1 abolished the binding of all three collagen types to Y. enterocolitica and type I and II collagens to Y. pseudotuberculosis. Full binding capacity was restored by introduction of the yopA gene into nonbinding Yersinia strains. Binding of type I, II, and IV collagens was expressed in Escherichia coli constructs harboring the yopA gene of either Y. enterocolitica or Y. pseudotuberculosis. The interaction of bacterial cells with type I collagen could be blocked by nonradiolabeled native collagens or denatured collagen but not with other serum and connective-tissue proteins. Unlabeled collagen could not displace bound radiolabeled collagen. The binding was inhibited by YOP1-specific polyclonal antibodies, in contrast to normal rabbit serum. The interaction was rapid and was quite resistant to heat treatment, to proteolytic enzymes, to various pHs in both acidic and alkaline ranges, and to the chaotropic agent urea. We propose that this newly identified interaction may be involved both in the first steps of the pathogenesis and in the complications of Yersinia infections affecting connective tissue. PMID- 2592348 TI - Erythromycin-induced ribosome stall in the ermA leader: a barricade to 5'-to-3' nucleolytic cleavage of the ermA transcript. AB - The Staphylococcus aureus ermA gene, whose product confers resistance to the macrolide-lincosamide-streptogramin B family of antibiotics, is induced at the level of translation by nanomolar concentrations of erythromycin. Erythromycin also specifically stabilizes ermA transcripts, and the induced stabilization requires in-phase translation of at least one of two small leader peptides in the 5' leader region of the transcript. Erythromycin-induced mRNA stabilization was tested in three constructions in which the ermA transcript was elongated by making insertions at the ermA transcription start. Whereas mRNA downstream of the leader peptide is stabilized by erythromycin, mRNA upstream is not. In the presence of erythromycin, specific mRNA decay intermediates in both the extended ermA genes and the wild-type ermA gene were detected by both Northern blotting and S1 nuclease mapping. The 5' ends of the intermediates map to the sequences that encode each of the two ermA leader peptides, suggesting that the intermediates are produced by stalled erythromycin-bound ribosomes acting as barricades to degradation by 5'-to-3' RNases. In addition, whereas erythromycin was found previously to stabilize ermA transcripts only physically, an ermC-cat 86 hybrid transcript was stabilized both physically and functionally by erythromycin. PMID- 2592349 TI - Substitution of a pentalenolactone-sensitive glyceraldehyde-3-phosphate dehydrogenase by a genetically distinct resistant isoform accompanies pentalenolactone production in Streptomyces arenae. AB - Pentalenolactone (PL), an antibiotic produced by Streptomyces arenae, is a potent inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The producer strain contains different isoforms of GAPDH: a PL-sensitive enzyme on nonproduction media and a PL-insensitive enzyme on production media. After induction of PL synthesis, the sensitive GAPDH disappears parallel to the disappearance of its activity, as shown by Western (immunoblot) hybridization. The two isoenzymes exhibit little immunological cross-reactivity and differ in size, amino acid composition, and several amino acid residues of their amino termini. Two different types of plasmids from a S. arenae genomic library, named pBRPLR1 and pBRPLR2, were cloned in Escherichia coli by selection for enhanced PL resistance. Both contain a GAPDH structural gene. Plasmid pBRPLR1 increases E. coli PL tolerance 7-fold, and plasmid pBRPLR2 increases it 30-fold. GAPDH from pBRPLR1 transformants shows biphasic PL inactivation kinetics. These cells contain PL-sensitive GAPDH from both E. coli and S. arenae. GAPDH from pBRPLR2 transformants tolerates higher PL concentrations than either E. coli or S. arenae PL-sensitive GAPDH but is less resistant than S. arenae PL-insensitive GAPDH. Nondenaturing polyacrylamide electrophoresis showed this GAPDH to be a hybrid of E. coli and S. arenae PL-insensitive GAPDH. The hybrid enzyme could be purified to homogeneity. Induction of the lacZ promoter of pUC subclones of both GAPDH genes had only a small effect on raising the level of intracellular GAPDH. PMID- 2592350 TI - Purification and characterization of S-adenosylhomocysteine deaminase from streptonigrin-producing Streptomyces flocculus. AB - An S-adenosylhomocysteine deaminase has been isolated and purified from streptonigrin-producing Streptomyces flocculus ATCC 13257. Deamination represents the major metabolic route of S-adenosylhomocysteine in this organism. The protein was found to be monomeric with a molecular weight of 56,100 +/- 1,600. The activity was optimal at pH 7.0 and 37 degrees C, and the deaminase was inactivated by p-chloromercuribenzoate but not by metal chelators. The Km for S adenosylhomocysteine is 2.5 mM, and the Ki for inhibition by deoxycoformycin is 1.6 nM. PMID- 2592351 TI - The Agrobacterium tumefaciens virC1 gene product binds to overdrive, a T-DNA transfer enhancer. AB - In Agrobacterium tumefaciens, a cis-active 24-base-pair sequence adjacent to the right border of the T-DNA, called overdrive, stimulates tumor formation by increasing the level of T-DNA processing. Recent results from our laboratory have suggested that the virC operon which enhances T-DNA processing probably does so because the VirC1 protein interacts with overdrive (N. Toro, A. Datta, M. Yanofsky, and E. W. Nester, Proc. Natl. Acad. Sci. USA 85:8558-8562, 1988). We report here the purification of the VirC1 protein from cells of Escherichia coli harboring a plasmid containing the coding sequences of the virC locus of the octopine Ti plasmid. By gel mobility shift and DNase I footprinting assays, we showed that this purified virC1 gene product binds to overdrive but not to the right border of T-DNA. PMID- 2592352 TI - Comparative amino acid sequence analysis of hemolysins produced by Vibrio hollisae and Vibrio parahaemolyticus. AB - Vibrio hollisae produces a hemolysin (Vh-rTDH) that is related to the thermostable direct hemolysin of Vibrio parahaemolyticus (Vp-TDH). Although both hemolysins are essentially similar biologically and immunologically, they differ markedly in heat stability; Vp-TDH is heat stable, whereas Vh-rTDH is heat labile. To elucidate the relationships between their characteristics and molecular structures, we analyzed the amino acid sequence of Vh-rTDH and compared it with that of Vp-TDH. Vh-rTDH consisted of 165 residues, of which 23 residues, spread over the peptide chain, differed from those of Vp-TDH. PMID- 2592353 TI - Developmental potential of Frankia vesicles. AB - The ability of nitrogenase-containing Frankia sp. strain CpI1 vesicles to regrow vegetative hyphae is demonstrated. Vesicles attached to hyphae in N2-fixing CpI1 cultures and sucrose gradient-isolated vesicles exhibited hyphal outgrowths when incubated in certain defined liquid media. Single or multiple hyphal extensions grew out from the vesicles. PMID- 2592354 TI - An initiation codon mutation in the apoC-II gene (apoC-II Paris) of a patient with a deficiency of apolipoprotein C-II. AB - We have identified the genetic defect that leads to a deficiency of apoC-II in the proband from the Paris kindred. Analysis of the apoC-IIParis DNA by Southern blot hybridization revealed no major gene rearrangements, but sequencing of polymerase chain reaction-amplified apoC-IIParis DNA revealed an A to G transition that changed the initiation AUG (methionine) codon to GUG (valine). Potential initiation of translation at the closest inframe methionine codon eliminates the entire signal peptide and the first 8 amino-terminal residues of apoC-II which would prevent apoC-II secretion into plasma. In agreement with this, no apoC-II was detected in the patient's plasma by radioimmunoassay or by two-dimensional gel electrophoresis and immunoblotting. Direct sequencing of amplified patient DNA from 12 different polymerase chain reaction samples demonstrated the presence of the A to G substitution in all, indicating that the proband is a homozygote for the defect. We propose that in the apoC-IIParis gene, a mutation in the initiation methionine codon prevents the normal initiation of apolipoprotein synthesis and leads to a deficiency of apoC-II. This initiation methionine mutation represents a new type of molecular defect that can result in Type I hyperlipoproteinemia. PMID- 2592355 TI - DNase I cleavage of branched DNA molecules. AB - We report here a potentially useful signature of branched DNA structures. The base 5' to the branch and the five bases flanking the 3' side of the branch site are protected from cleavage by DNase I in both three- and four-arm branched DNA molecules. Our procedure is to measure the cleavage profile for each 5' -labeled strand in a control duplex and compare this with that of the same strand in a branched structure under conditions yielding less than one cut per strand. The resulting cleavage pattern in an immobile four-arm junction is roughly 2-fold symmetric, consistent with the pattern of Fe(II).EDTA-induced cleavage that has been observed previously. In the three-arm junction, the DNase I cleavage pattern is asymmetric, indicating lack of 3-fold symmetry. A variable pattern of protection occurs to the 5' side of the branch in some strands only for both three- and four-arm junctions, extending 2-4 residues 5' to the branch. PMID- 2592356 TI - Isolation of a gene that encodes a new retinal protein, archaerhodopsin, from Halobacterium sp. aus-1. AB - We have cloned and sequenced the gene that encodes archaerhodopsin, a light driven H+ pump in Halobacterium sp. aus-1 (Mukohata, Y., Sugiyama, Y., Ihara, K., and Yoshida, M. (1988) Biochem. Biophys. Res. Commun. 151, 1339-1345). The nucleotide sequence of this gene contained an open reading frame which corresponded to a protein of 260 amino acids with a molecular mass of 27,851 daltons, including a precursor sequence of 6 amino acids at the amino terminus and 2 amino acids at the carboxyl terminus. The deduced amino acid sequence of archaerhodopsin exhibited 59 and 32% homology to the sequences of bacteriorhodopsin and halorhodopsin, respectively, from Halobacterium halobium. Three charged residues (Asp-121, Asp-218, and Lys-222) are conserved in the transmembrane segments among the three retinal proteins. Residues Asp-91 and Asp 102 which, it has been suggested, may be essential for the pumping of protons (Mogi, T., Stern, L. J., Marti, T., Chao, B. H., and Khorana, H. G. (1988) Proc. Natl. Acad. Sci. U. S. A. 85,4148-4152) are conserved between archaerhodopsin and bacteriorhodopsin. PMID- 2592357 TI - The distribution, purification, and pharmacological action of an amphibian neuromedin U. AB - The distribution, primary structure, and relative biological activity of neuromedin U has been determined from the frog Rana temporaria. Following sequential column chromatography of a gastrointestinal extract, the peptide was sufficiently pure to enable characterization by micro-sequence analysis. The entire sequence was found to be an icosapentapeptide which displays marked sequence similarity to both porcine and rat neuromedin U. The sequence of the biologically active, COOH-terminal region is almost completely conserved across all species. Synthetic, COOH-terminally amidated amphibian neuromedin U, like the porcine and rat peptides, stimulates rat uterine contraction in vitro thereby fulfilling the criterion upon which the nomenclature of this peptide family is based. In addition, the peptide demonstrates parallel pressor effects when infused systemically into rats. The high degree of amino acid sequence conservation is indicative of strong evolutionary pressure acting to retain the presence of this possibly physiologically important peptide across the vertebrate subphylum. PMID- 2592358 TI - Myristoylation, phosphorylation, and subcellular distribution of the 80-kDa protein kinase C substrate in BC3H1 myocytes. AB - Numerous reports have described a phosphoprotein with an apparent molecular mass of 68-87 kDa, often referred to as the 80K protein, which serves as a major specific substrate for protein kinase C in a wide variety of cell types. This protein has been shown to be myristoylated in macrophages, apparently in a stimulus-dependent manner. In the present study, we have defined the kinetics for myristoylation of the 80K protein in BC3H1 myocytes and have examined the subcellular distribution of the [3H]myristate and 32P-labeled forms of the protein before and after activation of protein kinase C by phorbol dibutyrate (PDBu). The 80K protein was identified in BC3H1 myocytes by apparent molecular mass of 68 kDa (consistent with the previously reported size of the murine homologue), isoelectric point of 4.6-4.8, PDBu-inducible phosphorylation, peptide mapping, and labeling with [3H]myristate. Incorporation of [3H]myristate by this protein occurred through an amide linkage and was abolished completely by cycloheximide. Pulse labeling of quiescent cells with [3H]myristate revealed no alteration in myristoylation of the 80K protein in either the crude membrane or soluble fractions after PDBu-induced phosphorylation. The subcellular distribution of this protein (approximately 80% membrane, approximately 20% cytosol) also was the same in control and PDBu-stimulated cells. Phosphorylation of both the membrane-bound and soluble forms was increased approximately 6-fold upon stimulation of cultures with PDBu; the soluble form was phosphorylated to a 4-fold higher stoichiometry than its membrane-bound counterpart. Together, these data demonstrate that the 80K protein is myristoylated cotranslationally in BC3H1 cells and that protein kinase C-dependent phosphorylation of the 80K protein does not alter its subcellular distribution or degree of myristoylation. The fact that 20% of total myristoylated 80K protein resides in the cytosol also indicates that myristoylation alone is not sufficient to target this protein to the plasma membrane. PMID- 2592359 TI - Changes in solubility, non-enzymatic glycation, and fluorescence of collagen in tail tendons from diabetic rats. AB - The increase in acid-insoluble collagen (AIC) from tail tendons of streptozotocin diabetic rats was measured and compared with that for control rats. AIC increased from 10% initially to 75% after 12 weeks of diabetes. It then increased slowly to 85% after 45 weeks. AIC for control rats was constant for the first 12 weeks and then increased slowly to 40% after 45 weeks. These data are consistent with an increase in the number of acid-stable cross-links in the collagen due to diabetes. The quantity of collagen solubilized by pepsin at 4 degrees C was unaltered due to diabetes, strong evidence that formation of diabetes-induced cross-links between helical regions of collagen molecules cannot explain the increase in AIC observed. Non-enzymatic glycation (NEG) increased linearly over 45 weeks, but the rate of NEG was much slower than the rate of increase in AIC observed for diabetics. The level of NEG for diabetics was about three times that for controls at a given time, but there was still less than 1 mol of glucose detected/mol of collagen at near maximum acid insolubility. Fluorescence associated with tail tendons was measured to test the hypothesis that fluorescent cross-links form as a consequence of NEG and result in decreased collagen solubility. Fluorescence (lambda ex 370; lambda em 430) increased slowly with age but was similar for control and diabetic tendons of the same age. Fluorescence was not increased in AIC compared with acid-soluble collagen derived from a given tendon sample. NEG of collagen reached near-diabetic levels in non-diabetic rats whose growth was inhibited by restricted feeding, but there was no associated increase in AIC. These data suggest that NEG and the subsequent formation of fluorescent cross-links do not contribute significantly to the rapid increase in AIC in the streptozotocin-rat model of diabetes. PMID- 2592360 TI - Changes in the cross-linking of collagen from rat tail tendons due to diabetes. AB - The acid solubility of Type I collagen from rat tail tendons decreases due to diabetes. This finding has been taken as evidence that collagen from diabetics may be more cross-linked than normal. We compared CNBr peptide maps prepared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis for [3H] NaBH4-reduced tail tendons from streptozotocin-diabetic rats with maps from age-matched control rats. At least through 30 weeks of diabetes, the distribution of mass of both cross-linked and uncross-linked CNBr peptides was identical in diabetic and control tendons. Therefore, the number of cross-linked peptides did not increase due to diabetes. We analyzed the 3H-cross-linking compounds present on the CNBr peptides and found that the 3H content of peptides cross-linked in control tendons through the bivalent, reduced cross-links hydroxylysinonorleucine and lysinonorleucine was diminished on corresponding peptides from diabetic tendons as a function of duration of diabetes. The cross-linked peptides, however, persisted. Therefore, we conclude that a larger fraction of these bivalent cross links is found in an unknown, non-reducible form in tendons from diabetic compared with control rats. This resembles a phenomenon normally associated with maturation and/or aging where the non-reducible form of the cross-links is acid stable. An increase in the fraction of the cross-links that is non-reducible and acid-stable would explain, at least in part, the decrease in acid solubility of the collagen. Non-enzymatic glycation (NEG) was not very specific, since most CNBr peptides bound some glucose. However, peptides from the alpha 2-chain seemed to be preferential targets for NEG. While NEG clearly increased due to diabetes, we found no evidence that increased NEG led to an increased number of cross-links in tail tendon collagen from streptozotocin diabetic rats. PMID- 2592361 TI - Characterization of two genes encoding human steroid 11 beta-hydroxylase (P 450(11) beta). AB - Steroid 11 beta-hydroxylase (P-450(11) beta) is a mitochondrial cytochrome P-450 enzyme necessary for cortisol biosynthesis. Deficiency of 11 beta-hydroxylase causes a hypertensive form of congenital adrenal hyperplasia. A partial cDNA clone encoding this enzyme has been previously isolated and the corresponding gene, CYP11B1, mapped to human chromosome 8q. This gene has now been isolated along with a second linked homologous gene, CYP11B2. Each gene contains nine exons. The eight introns are identical in location to the introns of the CYP11A gene encoding another mitochondrial P-450 enzyme, cholesterol desmolase, confirming that 11 beta-hydroxylase and cholesterol desmolase are in the same gene family within the P-450 superfamily. The nucleotide sequences of CYP11B1 and B2 are 95% identical in coding regions and about 90% identical in introns. The putative proteins encoded by CYP11B1 and B2 each contain 503 amino acids including a 24-residue signal peptide and have sequences that are 93% identical to each other and 75% identical to the predicted sequence of bovine P-450(11) beta. There are no obviously deleterious mutations in coding sequences of CYP11B2. However, the 5'-flanking regions of CYP11B1 and B2 have diverged considerably, and B2 transcripts were not detected in human adrenal mRNA or among cDNA clones. PMID- 2592362 TI - Insulin receptor aggregation and autophosphorylation in the presence of cationic polyamino acids. AB - Aggregation and autophosphorylation of the insulin receptor-protein kinase, from cultured 3T3-L1 adipocytes, were studied in the presence of cationic polyamino acids. Poly-L-lysine and poly-L-arginine produced the following effects with the purified receptor: first, the autophosphorylation rate was increased by polycations. Half-maximal stimulation was proportional to polymer length. The rate enhancement was greater at lower ATP concentrations. Second, near-endpoint (equilibrium) autophosphorylation was greater in the presence of the polycations. Polycations inhibited the reverse reaction: ADP + phosphoreceptor yielding ATP + aporeceptor. Third, the [32P]phosphopeptides generated by trypsin digestion of the 32P-beta-subunit, showed that no new autophosphorylation sites resulted from the presence of polycations. Fourth, the polycations, but not insulin, promoted receptor aggregation, and phosphoreceptor aggregated more readily than aporeceptor. Insulin receptor enriched through the wheat germ agglutinin eluate step was compared with purified receptor. Higher concentrations of poly-L arginine were required to stimulate autophosphorylation and to promote aggregation. Finally, several polycation-dependent substrates present in the wheat germ agglutinin eluate co-aggregated with the insulin receptor. Polycation stimulated receptor autophosphorylation is linked to a lower KM,app for ATP, but substrate phosphorylation may require the aggregation. PMID- 2592363 TI - Identification of a novel fatty acylated protein that partitions between the plasma membrane and cytosol and is deacylated in response to serum and growth factor stimulation. AB - Several proteins involved in transmembrane signaling have been shown previously to be modified covalently by long-chain fatty acids. Using the BC3H1 cell line, which contains a broad array of fatty acylated proteins, we have examined the possibility that acylation of certain proteins is modulated in response to mitogenic stimulation. In the present study, we describe a 64-kDa palmitoylated protein, referred to as p64, that is deacylated following stimulation of quiescent cells with fetal bovine serum, fibroblast growth factor, and phorbol dibutyrate. Western blot analysis of membrane and soluble fractions using a polyclonal antibody against p64 revealed that approximately 70% of p64 in unstimulated cells is present in the cytosol in a non-acylated form, whereas palmitoylated p64 is found exclusively in the membrane fraction. Extraction of membranes with 0.5 M sodium chloride, 0.2 M sodium pyrophosphate, or 0.2 M sodium carbonate failed to release p64, suggesting that the acylated form of this protein is tightly associated with membranes. Pulse labeling of proteins in quiescent cells with [3H] palmitate and subsequent chasing in medium containing 20% fetal bovine serum, fibroblast growth factor, or phorbol dibutyrate revealed that the fatty acid associated with p64 undergoes mitogen-stimulated turnover, whereas turnover of fatty-acid on other acylated proteins is not observed. Palmitate is the predominant fatty acid associated with p64; however, small amounts of covalent myristate are also detected. Both fatty acids are attached post-translationally to p64 through a hydroxylamine-sensitive linkage, suggesting that acylation of this protein is catalyzed by a palmitoyl transferase with relaxed specificity for fatty acid substrates. Together, these results suggest that palmitoylation may participate in the association of p64 with the plasma membrane and that mitogen-dependent deacylation might alter interactions between this protein and other membrane components. PMID- 2592364 TI - Unusual pattern of fatty acid biosynthesis. Evidence for C-19 desaturase activity in freshwater sponges. AB - The two long chain fatty acids common in marine demosponges, (5Z, 9Z)-5,9 hexacosadienoic (delta 5,9-26:2) and (5Z, 9Z, 19Z)-5,9,19-hexacosatrienoic (delta 5,9,19-26:3) acids), were identified also as the major phospholipid components in the freshwater sponge Ephydatia fluviatilis. Whereas the typical marine sponge Microciona prolifera biosynthesizes the delta 5,9,19-26:3 acid solely by homologation of exogenous palmitoleic acid (delta 9-16:1) and subsequent desaturation at positions 5 and 9, it was found that the freshwater sponge could further desaturate the delta 5,9-26:2 acid to the triene, indicating for the first time the existence of delta 19 -desaturase activity in a living organism. PMID- 2592365 TI - The 6S- and 6R-diastereomers of 5, 10-dideaza-5, 6, 7, 8-tetrahydrofolate are equiactive inhibitors of de novo purine synthesis. AB - The diasteromers of 5,10-dideaza-5,6,7,8-tetrahydrofolate (DDATHF) differing in chirality about carbon 6 were resolved and studied as inhibitors of folate dependent processes in mouse leukemia cells. Both diastereomers of DDATHF were found to be potent inhibitors of leukemia cell growth due to effects on de novo purine synthesis. Cell growth inhibition by these compounds was prevented by 5 formyltetrahydrofolate in a dose-dependent manner. This indicated that the effects of the DDATHF diastereomers were due to inhibition of folate-dependent processes. Metabolite reversal experiments indicated that 5' phosphoribosylglycinamide formyltransferase was the major site of action of these compounds in mouse cells. Another site in de novo purine synthesis was affected at higher concentrations of diastereomer B in L1210 cells. Low concentrations of both diastereomers were found to inhibit pure L1210 5'-phosphoribosylglycinamide formyltransferase competitively with the folate substrate. The two diastereomers were also efficient substrates for mouse liver folylpolyglutamate synthetase. We conclude that the 6R- and 6S-diastereomers of DDATHF are remarkably similar and equiactive antimetabolites inhibitory to de novo purine synthesis and that the biochemical processes involved in their cytotoxicity display little stereochemical specificity. PMID- 2592366 TI - The 2.4-A crystal structure of Scapharca dimeric hemoglobin. Cooperativity based on directly communicating hemes at a novel subunit interface. AB - The crystal structure of the cooperative dimeric hemoglobin from the arcid clam, Scapharca inaequivalvis, has been determined in the carbonmonoxy state. The phase problem was solved for reflections with Bragg spacings greater than 3 A using anomalous scattering from the porphyrin iron atoms measured at a single wavelength in combination with molecular averaging. The model built into this electron density map has been refined at 2.4 A resolution by means of stereochemically restrained least squares minimization to a conventional R-value of 0.156. The root mean square deviation from ideal bond lengths and angles are 0.013 A and 1.7 degrees, respectively. In addition to the 2336 hemoglobin atoms, 214 water molecules have been incorporated into the model. This structure reveals the details of an assemblage of two identical myoglobin-like subunits that is radically different from vertebrate hemoglobins. The subunit interface is formed by direct apposition of the E and F helices, whereas these surfaces are external in vertebrate hemoglobins. The interface has both hydrophobic and hydrophilic character. Two symmetrically related hydrophobic regions are formed between subunits. Six residues are involved in each of these regions that pack tightly enough to exclude water but have only a few atoms in close van der Waals contact. A number of ordered water molecules line the interface and form bridging hydrogen bonds between subunits. Four intersubunit ionic interactions are formed, two of which involve negatively charged propionate groups of the porphyrin. In contrast to cooperative vertebrate hemoglobins, a hydrogen bond network provides a direct route for communication between the two heme groups. PMID- 2592367 TI - Ligand binding to the dimeric hemoglobin from Scapharca inaequivalvis, a hemoglobin with a novel mechanism for cooperativity. AB - The homodimeric hemoglobin from Scapharca inaequivalvis has an unusual spatial arrangement of the subunits (Royer, W.E., Jr., Love, W.E., and Fenderson, F.F. (1985) Nature 316, 277-280). The time course of oxygen and nitric oxide rebinding to this protein following flash photolysis has been measured on a nanosecond time scale. A large amplitude is observed with a half-time of 20 ns (NO). With oxygen the half-time decreases from 70 ns at low fractional photolysis to 30 ns at large breakdown. The second order rate of NO binding is 1.6 x 10(7)/MS, and is the same as that for oxygen. Analysis of the geminate data suggests that oxygen and nitric oxide react more rapidly with the heme than in myoglobin, but also escape much more rapidly from its vicinity. PMID- 2592368 TI - Characterization of recombinant human antithrombin III synthesized in Chinese hamster ovary cells. AB - Biochemical and physiochemical properties of recombinant human antithrombin III were examined. This protein, produced in Chinese hamster ovary cells, showed a conformation apparently identical with the natural product isolated from human plasma when examined by circular dichroism, UV absorbance, and fluorescence spectroscopy. Comparison of the NH2-terminal sequences of recombinant and human plasma-derived antithrombin III showed that on synthesis and secretion of the recombinant protein from Chinese hamster ovary cells the signal peptide is correctly cleaved by the corresponding endoplasmic signal peptidase. The recombinant antithrombin III has identical properties in heparin binding and biological activities as determined in vitro by two-dimensional immunoelectrophoresis, progressive inhibitor, and heparin cofactor assays. Analysis of the carbohydrate portion of recombinant antithrombin III synthesized in Chinese hamster ovary cells revealed glycosylation of the complex type. Characterization of the oligosaccharide chains present in the recombinant protein reveals three major fractions, A (20%), B (60%), and C (20%). Fraction A contains tri- and tetraantennary complex-type oligosaccharides, fraction B contains biantennary oligosaccharides, and fraction C partially truncated biantennary structures. Pharmacokinetic studies with recombinant and plasma-derived antithrombin III in rabbits showed that the clearance behavior of both proteins is very similar and can be described by a double exponential decrease with almost identical kinetic parameters. PMID- 2592369 TI - Selective binding to DNA base pair mismatches by proteins from human cells. AB - Using the technique of delayed oligonucleotide migration through polyacrylamide gels, we have demonstrated that cell-free extracts of the human Burkitt's lymphoma cell line Raji contain proteins which can recognize and bind to mismatched single base pairs in short fragments of DNA. One of these binding proteins resembles an activity previously reported in HeLa cells (Jiricny, J., Hughes, M., Corman, N., and Rudkin, B. B. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 8860-8864) and recognizes DNA containing G.T mismatches. Extracts of Raji cells contain an additional activity which recognizes A.C, T.C, or T.T mismatches in DNA. This second binding protein can be distinguished from the G.T binding activity by its size, substrate specificity, and its fractionation properties. In addition to Raji cells, the new mismatch binding protein is present in extracts of human lymphoblastoid cell lines from a normal individual and a xeroderma pigmentosum patient as well as the SV40-transformed human fibroblast cell line MRC5V1. It seems likely that this novel activity is involved in a broad specificity DNA repair pathway for the correction of single base mismatches in human cells. PMID- 2592370 TI - The limits of the DNase I-sensitive domain of the human apolipoprotein B gene coincide with the locations of chromosomal anchorage loops and define the 5' and 3' boundaries of the gene. AB - In eukaryotic cells, chromatin is organized as domains or loops that are generated by periodic attachment of the chromatin fiber to protein components of a nuclear matrix, or scaffold. These chromosomal loops may have a function in gene regulation. The length of the chromatin domain encompassing the human apolipoprotein B gene was studied by determining the locations of nuclear matrix attachment sites as well as the boundaries of the DNase I-sensitive domain in cells that express the gene (such as HepG2 and CaCo-2 cells) and in those that do not (HeLa cells). Three nuclear matrix attachment regions (MARs) of the human apolipoprotein B gene have been localized: a 3' -proximal MAR, between nucleotides +43,186 and +43,850; a 5' -proximal MAR, between nucleotides -2,765 and -1,801; and a 5' -distal MAR, between nucleotides -5,262 and -4,048. Both the 3' -proximal and the 5' -distal MARS were present in cells that express the gene (HepG2 and CaCo-2 cells) as well as in cells that do not (HeLa cells), whereas the 5' -proximal MAR was detected only in HepG2 cells. These MARs were located at the bases of chromosomal loops in histone-extracted nuclei in all three cell lines. Various classes of A/T-rich sequences resembling the recognition site for topoisomerase II were present within the MAR-containing fragments. The boundaries of the DNase I-sensitive domain coincide with the positions of the 3' -proximal and 5' -distal matrix attachment sites. These results suggest the existence of a 47.5-kilobase domain that represents a topologically sequestered functional unit containing the coding region and all known cis-acting regulatory elements of the human apolipoprotein B gene. PMID- 2592371 TI - Phosphorylation of smooth muscle myosin heavy and light chains. Effects of phorbol dibutyrate and agonists. AB - A number of different protein kinases phosphorylate purified heavy chains or the 20-kDa light chain of smooth muscle myosin. The physiological significance of these phosphorylation reactions has been examined in intact smooth muscle. Myosin heavy chain was slightly phosphorylated (0.08 mol of phosphate/mol) under control conditions in bovine tracheal tissue. Treatment with carbachol, isoproterenol, or phorbol 12,13-dibutyrate resulted in no significant change. In contrast, heavy chain was phosphorylated to 0.30 mol of phosphate/mol of heavy chain in tracheal smooth muscle cells in culture. This value increased significantly with ionomycin treatment. In control tissues, 9% of the light chain was monophosphorylated with 32P in the serine site phosphorylated by myosin light chain kinase. Carbachol (0.1 microM) alone resulted in contraction and 42% monophosphorylated light chain with 32P only in the serine site phosphorylated by myosin light chain kinase. Similarly, stimulation with histamine, 5-hydroxytryptamine, or KCl resulted in 32P incorporation into only the myosin light chain kinase serine site. Phorbol 12,13-dibutyrate (1 microM) alone resulted in 22% monophosphorylated light chain. However, only 25% of the 32P was in the myosin light chain kinase serine site, whereas 75% was in a serine site phosphorylated by protein kinase C. Phorbol 12,13-dibutyrate plus carbachol resulted in 27% monophosphorylated light chain; 75% of the 32P was in the myosin light chain kinase serine site, with the remainder in the protein kinase C serine site. These results indicate that phorbol esters act to increase phosphorylation of myosin light chain by protein kinase C. However, receptor-mediated stimulation or depolarization leading to tracheal smooth muscle contraction results in phosphorylation of myosin light chain by myosin light chain kinase alone. PMID- 2592372 TI - Transcriptional repression of the mouse dihydrofolate reductase gene during muscle cell commitment. AB - A differentiation-competent mouse muscle cell line containing 50-100-times the diploid number of dihydrofolate reductase (DHFR) genes was used to study regulation of DHFR mRNA levels during myogenic withdrawal from the cell cycle. Quantitative RNase protection assays showed DHFR mRNA levels decreased 15-fold during commitment; DHFR pre-mRNA levels decreased 7-fold. Concomitantly, transcription products were analyzed by hybridization to Southern blots of dhfr containing plasmids. Control run-on assays performed on nonamplified parental cells indicated that run-on signals measured in amplified cells were dhfr amplicon-specific. Run-on signals were sensitive to alpha-amanitin, indicating RNA polymerase 2 specificity, and did not hybridize to pBR322 sequences, demonstrating hybridization stringency. Comparison of run-on signals hybridizing to DNA fragments representing either the 5' end of the gene or the entire gene showed that transcriptional repression occurred within the first 660 bases of the 30-kilobase gene, consistent with regulation at the level of either initiation or early pretermination. In contrast to the DHFR gene, DNA 5' to all but the first few bases of the DHFR coding region (between -1000 and +60 base pairs from the preferred cap site) showed strong run-on transcription in both proliferative and committed cells. Northern blot analysis using a probe complementary both to the dhfr coding region and the upstream region showed a uniform decrease in all detectable transcripts. No commitment-dependent changes in dhfr cap site usage, splicing, or polyadenylylation site usage were detected. Our results support a transcriptional model for regulation of DHFR mRNA levels. PMID- 2592373 TI - Blood clotting factor IX BM Nagoya. Substitution of arginine 180 by tryptophan and its activation by alpha-chymotrypsin and rat mast cell chymase. AB - Factor IX BM Nagoya (IX Nagoya) is a natural mutant of factor IX responsible for severe hemophilia B. A patient with this mutant is characterized by a markedly prolonged ox brain prothrombin time. IX Nagoya was purified from the patient's plasma by immunoaffinity chromatography with an anti-factor IX monoclonal antibody column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that treatment of IX Nagoya with factor XIa/Ca2+ resulted in cleavage only at the Arg145-Ala146 bond. Reversed-phase high performance liquid chromatography of a trypsin digest of IX Nagoya showed an aberrant peptide, which was further digested with proteinase Asp-N. Primary structure analysis of one of the Asp-N peptides revealed that Arg180 is replaced by Trp. An essentially complete (99%) amino acid sequence of IX Nagoya was obtained by sequencing fragments derived from a lysyl endopeptidase digest in which no other substitutions in the catalytic triad or substrate binding site were found. We also found that IX Nagoya is activated by alpha-chymotrypsin or rat mast cell chymase by monitoring the rate of factor X activation using a fluorogenic peptide substrate in the presence of factor VIII, phospholipids, and Ca2+. These results indicate that the substitution of Arg180 by Trp impairs the cleavage by factor XIa required for activation of this zymogen and that the substitution causes hemophilia BM. PMID- 2592374 TI - Protein and carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry. AB - The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. These studies corroborated 95% of the 369-amino acid-long sequence and established the fidelity of translation of the NH2 and COOH terminal including the absence of "ragged ends." The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. No other arrangements of disulfides were detected. Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups and an additional hexose-hexosamine unit were detected by high performance anion-exchange chromatography. PMID- 2592375 TI - Interaction of tubulin and cellular microtubules with the new antitumor drug MDL 27048. A powerful and reversible microtubule inhibitor. AB - We have characterized the binding of trans-1-(2,5-dimethoxyphenyl)-3-[4 (dimethylamino)phenyl]-2-methyl-2- propen- 1-one (MDL 27048) to purified procine brain tubulin, and the inhibition of microtubule assembly by this compound in vitro and using cultured cells. Binding measurements were performed by difference absorption and fluorescence spectroscopy. MDL 27048 binds to one site/tubulin heterodimer with an apparent equilibrium constant Kb = (2.8 +/- 0.8) X 10(6) M-1 (50 mM 2-(N-morpholino)ethanesulfonic acid, 1 mM [ethylenebis(oxyethylenenitrilo)]tetraacetic acid, 0.5 mM MgCl2, 0.1 mM GTP buffer, pH 6.7, at 25 degrees C). Podophyllotoxin displaced the binding of MDL 27048, suggesting an overlap with the colchicine-binding site. Assembly of purified tubulin into microtubules was inhibited by substoichiometric concentrations of MDL 27048, which also induced a slow depolymerization of preassembled microtubules. The cytoplasmic microtubules of PtK2 cells were disrupted in a concentration and time-dependent manner by MDL 27048, as observed by indirect immunofluorescence microscopy. Maximal depolymerization took place with 2 X 10(-6) M MDL 27048 in 3 h. When the inhibitor was washed off from the cells, fast microtubule assembly (approximately 8 min) and complete reorganization of the cytoplasmic microtubule network (15-30 min) were observed. MDL 27048 also induced mitotic arrest in SV40-3T3 cell cultures. Due to all these properties, this anti-tumor drug constitutes a new and potent microtubule inhibitor, characterized by its specificity and reversibility. PMID- 2592376 TI - Reaction of human skin chymotrypsin-like proteinase chymase with plasma proteinase inhibitors. AB - The ability of plasma proteinase inhibitors to inactivate human chymase, a chymotrypsin-like proteinase stored within mast cell secretory granules, was investigated. Incubation with plasma resulted in over 80% inhibition of chymase hydrolytic activity for small substrates, suggesting that inhibitors other than alpha 2-macroglobulin were primarily responsible for chymase inactivation. Depletion of specific inhibitors from plasma by immunoadsorption using antisera against individual inhibitors established that alpha 1-antichymotrypsin (alpha 1 AC) and alpha 1-proteinase inhibitor (alpha 1-PI) were responsible for the inactivation. Characterization of the reaction between chymase and each inhibitor demonstrated in both cases the presence of two concurrent reactions proceeding at fixed relative rates. One reaction, which led to inhibitor inactivation, was about 3.5 and 4.0-fold faster than the other, which led to chymase inactivation. This was demonstrated in linear titrations of proteinase activity which exhibited endpoint stoichiometries of 4.5 (alpha 1-AC) and 5.0 (alpha 1-PI) instead of unity, and SDS gels of reaction products which exhibited a banding pattern indicative of both an SDS-stable proteinase-inhibitor complex and two lower Mr inhibitor degradation products which appear to have formed by hydrolysis within the reactive loop of each inhibitor. At inhibitor concentrations approaching those in plasma where inhibitor to chymase concentration ratios were in far excess of 4.5 and 5.0, the rate of chymase inactivation by both serpin inhibitors appeared to follow pseudo-first order kinetics. The "apparent" second order rate constants of inactivation determined from these data were about 3000-fold lower than the rate constants reported for human neutrophil cathepsin G and elastase with alpha 1-AC and alpha 1-PI, respectively. This suggests that chymase would be inhibited about 650-fold more slowly than these proteinases when released into plasma. These studies demonstrate that although chymase is inactivated by serpin inhibitors of plasma, both inhibitors are better substrates for the proteinase than they are inhibitors. This finding along with the slow rates of inactivation indicates that regulation of human chymase activity may not be a primary function of plasma. PMID- 2592377 TI - The interaction of thrombospondin with platelet glycoprotein GPIIb-IIIa. AB - The interaction of human platelet thrombospondin (TSP) with human platelet glycoproteins GPIIb-IIIa was studied using a solid-phase binding assay. Polystyrene test tubes were coated with TSP, and 125I-labeled GPIIb-IIIa was added, allowed to bind, and the bound radioactivity was measured. After 90 min, the binding became time independent, and in most experiments, more than 10% of the exogenously added radioactivity was bound to the tube. Analysis of the bound radioactivity by polyacrylamide gel electrophoresis and autoradiography indicated that it was from labeled GPIIb-IIIa. Several lines of evidence indicate that the binding of GPIIb-IIIa to TSP was specific. (a) TSP immobilized on plastic or Sepharose bound 3-10-fold more GPIIb-IIIa than immobilized bovine serum albumin. (b) Addition of unlabeled excess GPIIb-IIIa reversed the binding of 125I-labeled GPIIb-IIIa to immobilized TSP. (c) Addition of EDTA inhibited the binding of GPIIb-IIIa to TSP by more than 90%, whereas addition of 1 mM CaCl2 and 1 mM MgCl2 potentiated the binding by more than 100%. (d) Monoclonal antibodies against TSP and GPIIb-IIIa inhibited the binding by 30-70% as compared with control and polyclonal anti-fibrinogen anti-serum. (e) A plot of GPIIb-IIIa bound versus GPIIb-IIIa added was best described as a rectangular hyperbola by regression analysis with half-saturation at 60 ng/ml GPIIb-IIIa. Similar results were obtained when labeled TSP was added to tubes coated with GPIIb-IIIa. These results show that TSP and GPIIb-IIIa can specifically interact in vitro and suggest that GPIIb-IIIa may function as a platelet TSP receptor during platelet aggregation. PMID- 2592378 TI - Induced bending of plasmid pLS1 DNA by the plasmid-encoded protein RepA. AB - The broad host range streptococcal plasmid pLS1 encodes for a 5.1-kDa repressor protein, RepA. This protein has affinity for DNA (linear or supercoiled) and is translated from the same mRNA as the replication initiator protein RepB. By gel retardation assays, we observed that RepA shows specificity for binding to the plasmid HinfID fragment, which includes the target of the protein. The target of RepA within the plasmid DNA molecule has been located around the plasmid single site ApaLI. This site is included in a region that contains the promoter for the repA and repB genes and is contiguous to the plasmid ori(+). A complex sequence directed DNA curvature is observed in this region of pLS1. Upon addition of RepA to plasmid linear DNA or to circularly permuted restriction fragments, this intrinsic curvature was greatly enhanced. Thus, a strong RepA-induced bending could be located in the vicinity of the ApaLI site. Visualization of the bent DNA was achieved by electron microscopy of complexes between RepA and plasmid DNA fragments containing the RepA target. PMID- 2592379 TI - Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells. AB - The present study has examined the effect of elevated glucose levels on membrane lipid peroxidation and osmotic fragility in human red blood cells (RBC). Defibrinated whole blood or RBC were incubated with varying concentrations of glucose at 37 degrees C for 24 h. RBC incubated with elevated levels of glucose showed a significantly increased membrane lipid peroxidation when compared with control RBC. A significant positive correlation was observed between the extent of glucose-induced membrane lipid peroxidation and the osmotic fragility of treated RBC. Glucose-induced membrane lipid peroxidation and osmotic fragility were blocked when RBC were pretreated with fluoride, an inhibitor of glucose metabolism; with vitamin E, an antioxidant; with para-chloromercurobenzoate and metyrapone, inhibitors of the cytochrome P-450 system; or with dimethylfurane, diphenylamine, and thiourea, scavengers of oxygen radicals. RBC treated with elevated glucose concentrations also showed an increase in NADPH levels. Exogenous addition of NADPH to normal RBC lysate induced membrane lipid peroxidation similar to that observed in the glucose-treated RBC. These data suggest that elevated glucose levels can cause the peroxidation of membrane lipids in human RBC. PMID- 2592380 TI - Induction of mineral deposition by primary cultures of chicken growth plate chondrocytes in ascorbate-containing media. Evidence of an association between matrix vesicles and collagen. AB - A serum-free primary culture system for chicken growth plate chondrocytes has been developed which consistently undergoes mineral deposition. Upon attainment of confluency, the chondrocytes develop locally into multilayer cellular nodules leading to matrix calcification. Mineralization first occurs in matrix vesicles (MV) that are abundant in the extraterritorial matrix between the hypertrophic cells. Studies with 45Ca reveal that significant accumulation of Ca2+ occurs as early as day 12, continuing progressively throughout the culture period. By day 24, the nodules become densely calcified. Fourier transform infrared spectroscopy reveals the mineral to be similar to apatite, with features essentially identical to those of mineral formed by MV in vitro. The presence of ascorbate is critical to the culture system; in its absence, calcification is rarely observed. Ascorbate stimulates MV formation and synthesis of cellular protein, alkaline phosphatase, and especially types II and X collagens. In addition, there is strong evidence that the types II and X collagens are associated with MV. 1) Electron microscopy reveals MV embedded in a type II collagenous network; 2) Western blots of sodium dodecyl sulfate-polyacrylamide gel electrophoresis of MV using monospecific antibodies to types X and II collagen indicate that both collagens are present in specific MV fractions; 3) sucrose gradient purification of MV does not remove associated collagens; 4) graded salt extraction selectively releases type II collagen from MV; and 5) incubation of radiolabeled types II and X collagens with MV leads to their cosedimentation upon subsequent centrifugation. Taken together, the data suggest that coordinated synthesis of the collagens, alkaline phosphatase, MV formation, and Ca2+ accumulation by the cultures combine to induce mineral deposition in the multilayer nodules. PMID- 2592381 TI - Bromouridine triphosphate inhibits transcription termination and mRNA release by vaccinia virions. AB - Termination of transcription in vitro by purified vaccinia virus RNA polymerase occurs downstream of a cis-acting signal UUUUUNU in the nascent RNA strand and requires a trans-acting termination factor, VTF, that is associated with the viral mRNA capping enzyme. Factor-dependent termination can be inhibited specifically by incorporation of BrUMP (from BrUTP) into nascent RNA in place of UMP. The relevance of VTF action to early vaccinia mRNA biogenesis was demonstrated in the present study of the effects of BrUTP on mRNA synthesis and release by permeabilized vaccinia virions. BrUMP incorporation inhibited the release of newly made transcripts from the virus particle, resulting in the accumulation of transcripts within virus cores. This effect was observed also with IUMP, but not with BrCMP or IMP incorporation. Transcripts synthesized in the presence of BrUTP were heterogeneous in size and severalfold larger than transcripts made in the presence of UTP. The progressive increase in the size of the core-associated, BrUMP-containing transcripts indicated that they were still engaged by elongating RNA polymerase. These results are consistent with a predominant pathway of mRNA 3'-end formation by virions that involves VTF dependent transcription termination. These data do not support an alternative model of 3'-end formation by endonucleolytic cleavage of larger RNA precursors. PMID- 2592382 TI - Testins are structurally related Sertoli cell proteins whose secretion is tightly coupled to the presence of germ cells. AB - Previous studies from this laboratory have shown that Sertoli cell-enriched culture medium contained two immunologically and structurally related proteins designated CMB-22 and CMB-23 with Mr of 37,000 and 40,000, respectively. We have now demonstrated that both CMB-22 and CMB-23 are monomeric proteins with the following NH2-terminal amino acid sequences: CMB-22, NH2 TPDPSLDVEWNEWRTKHGKTYNMNEERLKR; CMB-23, NH2-XAPXPDPSLDVEXNEXRTK. These sequences are virtually identical except that CMB-23 has three extra NH2 terminus amino acids of X-A-P. Comparison of these sequences with those in the Protein Identification Resource revealed that they are unique proteins. CMB-22 and CMB-23 are highly concentrated in testes and their levels in this tissue increase with age. Studies using [35S]methionine incorporation and immunoprecipitation demonstrated that Sertoli cells synthesize and secrete these proteins in vitro. Because they seem not to have been isolated previously, are concentrated in and synthesized by the testes, and are structurally related, we propose that CMB-22 and CMB-23 be designated testin I and testin II, respectively. The distribution of these proteins in biological fluids were compared with those of testibumin and rat androgen binding protein (rABP), two other Sertoli cell proteins. The results suggest that testins, unlike testibumin and rABP, are not transported to the epididymis. Although the amount of testins secreted by Sertoli cells in vitro is similar to that of testibumin and rABP, the concentrations in testis and rete testis fluid are several orders of magnitude less than that of testibumin and rABP. These observations suggest that the secretion of these proteins in vivo might be suppressed by germ cells. The fact that 10 times more testins are secreted by tubules from immature rats than by those from adult rats and that there is an increase in the testicular content of testins following a single dose of busulfan, which depleted the germ cells from the seminiferous epithelium, supports this hypothesis. Thus, the secretion of testins by Sertoli cells appears to be tightly coupled to the presence of germ cells; there is an inverse relationship between the amount of testins in the testis and the number of germ cells. These results suggest that testins are unique testicular proteins that can be used to study Sertoli cell-germ cell interactions in the seminiferous epithelium. PMID- 2592383 TI - Crystals of fasciculin 2 from green mamba snake venom. Preparation and preliminary x-ray analysis. AB - Fasciculin 2 from the venom of the green mamba, Dendroaspis angusticeps, has been crystallized. The crystals are tetragonal, with unit cell dimensions a = 48.9 A and c = 82.0 A, space group P 41 21 2 or P 43212. Density measurements and pseudocentering of the hko zone indicate that there are 16 molecules in the unit cell. PMID- 2592384 TI - 5-Fluorouracil inhibits dihydrofolate reductase precursor mRNA processing and/or nuclear mRNA stability in methotrexate-resistant KB cells. AB - This laboratory previously reported that 5-fluorouracil (FUra) increases dihydrofolate reductase (DHFR) precursor mRNA (pre-mRNA) levels relative to DHFR mRNA levels in a methotrexate-resistant KB cell line; these data suggested that incorporation of FUra into RNA may, in part, lead to cell death through the inhibition of mRNA processing (Will, C. L., and Dolnick, B.J. (1987) J. Biol. Chem. 262, 5433-5436). Utilizing a methotrexate-resistant KB cell line designated 1BT, we now report the kinetic basis for altered levels of DHFR RNA observed in FUra-treated cells. Long-term exposure to FUra had no effect on the steady-state level of DHFR pre-mRNA containing intron V or I. However, steady-state levels of total DHFR mRNA decreased 2.0-fold on a per cell basis in cells exposed to 1.0 microM FUra. No significant change in the half-life of total DHFR mRNA or pre mRNA was observed in cells exposed to FUra (t1/2 = approximately 11.5 h and 50 min, respectively). Nuclear/cytoplasmic RNA labeling experiments demonstrated that the rate of nuclear DHFR RNA conversion to cytoplasmic DHFR mRNA decreased approximately 1.8-fold in FUra-treated cells. These results provide further evidence the FUra may inhibit processing of mRNA precursors and/or affect the stability of nuclear DHFR mRNA. PMID- 2592385 TI - Closed shortening of the femur. AB - Twenty skeletally mature patients (average age, sixteen years and seven months; range, thirteen years and seven months to twenty-two years and four months) were treated for limb-length inequality by closed shortening of the femur. Preoperatively, the amount of femoral shortening that was necessary to level the pelvis was determined radiographically by balancing the pelvis with calibrated lifts under the shorter extremity. All twenty shortening procedures were performed with an intramedullary cam saw and insertion of an intramedullary rod through a gluteal incision; no additional incisions were needed to complete the procedure. At the most recent follow-up, the limb-length discrepancy was one centimeter or less in all twenty patients. All patients reported that the limbs seemed to be of equal length and that the pelvis felt level. PMID- 2592386 TI - Treatment of sequestra, pseudarthroses, and defects in the long bones of children who have chronic hematogenous osteomyelitis. AB - We reviewed the results, after follow-up ranging from twenty-three months to six years, in thirty-four patients who were treated during childhood for hematogenous osteomyelitis of a major long bone complicated by sequestration of a portion of the diaphysis and by pseudarthrosis or segmental bone loss, or both. Of the thirty-four lesions, twenty-four were in the tibia, eight were in the femur, and two were in the humerus. In twenty-three patients (Group I), the infection was still active, while in the other eleven (Group II), it was quiescent at the time of admission to the hospital. In nine of the patients in Group I (four tibial and five femoral lesions), an involucrum bridged the osseous defect, indicating that the periosteal tube had not been destroyed. In these nine patients, sequestrectomy and debridement, appropriate antibiotic therapy, and prolonged immobilization in a plaster cast resulted in healing of the defect without recurrence of the infection. In the remaining fourteen patients (twelve tibial and two femoral lesions), there was no periosteal new-bone formation, and operative treatment consisted of two stages: the first, to resolve the infection, and the second, to heal the osseous defect with corticocancellous iliac grafts. In the eleven patients in Group II (eight tibial, one femoral, and two humeral lesions), there were no involucra. All of these patients were treated with cancellous bone grafts and prolonged immobilization. In twenty-two of the thirty four patients (thirteen in Group I and nine in Group II), there were varying degrees of angular deformity at the pseudarthrosis, necessitating correction by manipulation when the plaster cast was applied postoperatively (ten patients), by fibular transposition (six patients), or by fibular osteotomy in addition to manipulation (six patients). Excluding complications specific to the fibular transfer procedure, the complications in the Group-I patients (six recurrent postoperative infections, one fracture of the graft, and one non-union of a fibular strut graft) were approximately as frequent as those in the Group-II patients (one failure of fusion and two fractures of the graft). Operative treatment resulted in healing of all but one tibial lesion, in a patient who nonetheless had good function at follow-up. Of the seven limb-length discrepancies of 2.8 centimeters or more, by the latest follow-up two had been treated uneventfully: one by femoral and the other by tibial lengthening.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2592387 TI - The fate of acetabular allografts after bipolar revision arthroplasty of the hip. A radiographic review. AB - We reviewed the radiographs of thirty-one patients (thirty-two hips) who had had revision of the acetabular component of a total hip arthroplasty with a bipolar socket supplemented by allograft and were followed for twenty-four to forty-eight months. The grafts were categorized according to their consistency (solid or crushed bone), the location of the acetabular defect (peripheral [rim] or central), and the extent of the acetabular defect (contained--the medial part of the acetabular wall was intact, or non-contained--it was deficient). We recorded the time to incorporation of the graft, the amount of migration of the socket in the superior and medial axes, and the percentage of graft remaining at the time of the most recent follow-up. The time to healing was similar for all categories of grafts. The central, contained, solid grafts had less resorption than did the central, contained, crushed-bone grafts, as evidenced by less migration of the socket during follow-up. The non-contained grafts, in both peripheral and central locations, were associated with high rates of migration and of instability of the socket. PMID- 2592388 TI - Primary and revision total hip replacement without cement and with associated femoral osteotomy. AB - Nine porous-coated total hip prostheses were implanted without cement in nine patients who had a major proximal femoral deformity. Six patients had revision and three, primary total hip replacement. In all nine patients, as well placed corrective osteotomy was needed to successfully perform the arthroplasty. The average time until union of the proximal femoral osteotomy was fifteen weeks for the patients who had a primary arthroplasty and twenty-seven weeks for the patients who had a revision arthroplasty. The average Harris hip-rating score was 94 points for the patients who had a primary arthroplasty and 84 points (range, 60 to 93 points) for those who had a revision arthroplasty. The length of follow up averaged forty-seven months. PMID- 2592389 TI - Charnley total hip arthroplasty with cement. Fifteen-year results. AB - The results of the first 333 Charnley total hip arthroplasties that were performed with cement at the Mayo Clinic were reviewed a minimum of fifteen years postoperatively. Data were available for 166 of 170 hips of patients who were still alive. One hundred and thirty patients died, and thirty-seven hips were revised. At the time of this study, 80 per cent of the living patients had no pain, and 152 of the 160 hips remained much better than before the operation. Kaplan-Meier analysis of probable loosening of one or both components, on the basis of roentgenographic evidence, demonstrated a probability of loosening of 3 per cent incidence at one year after operation, 13 per cent at five years, 19 per cent at ten years, and 32 per cent at fifteen years. The probability of failure (that is, revision or symptomatic loosening) was 0.9 per cent at one year, 4.1 per cent at five years, 8.9 per cent at ten years, and 12.7 per cent at fifteen years. We did not identify a dramatic increase in the incidence of loosening or failure at any of the follow-up periods (one, five, ten, or fifteen years). With the Mayo Clinic clinical and roentgenographic system for scoring the hips, we found that ninety-seven hips had a good or excellent result; fifteen, a fair result; and thirteen, a poor result. (The scoring could not be completed for forty-one hips). The functional results deteriorated slightly over time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592390 TI - Displaced intra-articular fractures of the tarsal navicular. AB - Between 1980 and 1987, twenty-one patients who had a displaced fracture of the body of the tarsal navicular were treated with open reduction and internal fixation. A classification system was devised on the basis of the direction of the fracture line, the pattern of disruption of the surrounding joints, and the direction of displacement of the foot. In a Type-1 injury, the fracture line is in the coronal plane and there is no angulation of the fore part of the foot. In a Type-2 fracture, the primary fracture line is dorsal-lateral to plantar-medial, and the major fragment and the fore part of the foot are displaced medially. In a Type-3 injury, there is a comminuted fracture in the sagittal plane of the body of the tarsal navicular, and the fore part of the foot is laterally displaced. Satisfactory reduction, which was defined as restoration of more than 60 per cent of the joint surface in the anteroposterior and lateral planes, was achieved in all Type-1 injuries, 67 per cent of the Type-2 fractures, and 50 per cent of the Type-3 fractures. Radiographic evidence of healing was seen at an average of 8.5 weeks after injury. At an average follow-up of forty-four months (range, twelve to 106 months), a good result was noted in fourteen patients (67 per cent); a fair result, in four (19 per cent); and a poor result, in three (14 per cent). Both the type of fracture and the accuracy of the operative reduction directly correlated with the final clinical outcome. PMID- 2592391 TI - Recalcitrant chronic adhesive capsulitis of the shoulder. Role of contracture of the coracohumeral ligament and rotator interval in pathogenesis and treatment. AB - Seventeen patients who had recalcitrant chronic adhesive capsulitis were operated on between 1979 and 1986 and were followed for an average of 6.8 years. At operation, the major cause of the restricted glenohumeral movement was found to be contracture of the coracohumeral ligament and rotator interval. Release of the contracted structures relieved pain and restored motion of the shoulder in all patients. Histological study showed fibrosis, hyalinization, and fibrinoid degeneration in the contracted connective tissues, as well as fibrosis of the subsynovial tissue and an absence of the synovial cell layer on the joint side of the rotator interval. The contracture of the coracohumeral ligament and rotator interval appears to be the main lesion in chronic adhesive capsulitis. Resection of these structures, combined with appropriate exercise, will relieve pain and restore motion to the shoulder. PMID- 2592392 TI - Septic arthritis of the shoulder in adults. AB - Septic arthritis of the shoulder is uncommon in adults. We reviewed the cases of eighteen patients who were followed for a minimum of one year. The patients ranged in age from forty-two to eighty-nine years. All but one patient had at least one serious associated disease. Eight patients had had an injection or aspiration of the shoulder before development of the infection. All but one patient had had a delay in diagnosis. At the time of admission to the hospital, the erythrocyte sedimentation rate was always elevated, but the body temperature and white blood-cell count were not. After treatment, the functional result was usually poor: only five patients regained forward flexion to 90 degrees or more, eight patients had no active motion of the glenohumeral joint, and two patients died. Arthrotomy appeared to afford a better result than did repeated aspiration. PMID- 2592393 TI - Treatment of dislocation of the hip, detected in early childhood, based on magnetic resonance imaging. AB - In seven children in whom congenital dislocation of the hip was diagnosed after they began to walk, magnetic resonance imaging provided important information for treatment. In five children, it revealed adhesion of the capsule to the ilium, an inverted limbus, and a displaced transverse ligament; these findings indicated a need for open reduction. In the other two children, magnetic resonance imaging demonstrated that the capsule was redundant and appeared to have been stripped from the posterosuperior part of the acetabular rim; this allowed closed reduction. Repeat magnetic-resonance imaging in these two hips suggested that the capsule gradually shrank after several months. The findings in these two patients suggested a long-standing Grade-I congenital dislocation of the hip, as described by Dunn and by Ogden. Children who have this type of congenital dislocation can be treated with closed reduction, provided there is prolonged immobilization of the hip. PMID- 2592395 TI - Use of the Greenfield filter to prevent fatal pulmonary embolism associated with total hip and knee arthroplasty. AB - We inserted a Greenfield filter prophylactically in forty-two of approximately 4,000 patients who were about to have a total hip or knee replacement, or both, and who were at high risk for pulmonary embolism (Group I). The filter was implanted postoperatively in twenty-four additional patients who had thromboembolic complications or in whom anticoagulation was contraindicated (Group II). None of the patients in Group I and only one in Group II had a fatal pulmonary embolism. Use of the Greenfield filter is a safe, easy, and effective method of preventing fatal pulmonary embolism in selected patients: those who are at exceptionally high risk for thromboembolism, as a method of preoperative prophylaxis; those who have had a thromboembolism and in whom therapeutic anticoagulation is contraindicated; and those who have complications secondary to therapeutic anticoagulation. PMID- 2592396 TI - Compartment syndrome complicating use of the hemi-lithotomy position during femoral nailing. A report of two cases. PMID- 2592394 TI - Polymethylmethacrylate-induced release of bone-resorbing factors. AB - A pseudomembranous structure that has the histological characteristics of a foreign-body-like reaction invariably develops at the bone-cement interface in the proximity of resorption of bone around aseptically loosened cemented prostheses. This study was an attempt to implicate polymethylmethacrylate in this resorptive process. Unfractionated peripheral-blood mononuclear cells (consisting of lymphocytes and monocytes) and surface-adherent cells (monocyte-enriched) were prepared from control subjects who did and did not have clinical evidence of osteoarthrosis and from patients who had osteoarthrosis and were having a revision for failure of a cemented hip or knee implant. Cells were cultured for varying periods in the presence and absence of nonpolymerized methacrylate (one to two-micrometer spherules), pulverized polymerized material, or culture chambers that were pre-coated with polymerized cement. Conditioned media that were derived from both methacrylate-stimulated cell populations were shown to contain specific bone-resorbing mediators (interleukin-1, tumor necrosis factor, or prostaglandin E2) and to directly affect bone resorption in 45Ca-labeled murine limb-bone assays. PMID- 2592397 TI - Locked scapula. A case report. PMID- 2592398 TI - Subluxation of the patella. Computed tomography analysis of patellofemoral congruence. PMID- 2592399 TI - Stable nuclear transformation of Chlamydomonas using the Chlamydomonas gene for nitrate reductase. AB - We have developed a nuclear transformation system for Chlamydomonas reinhardtii, using micro-projectile bombardment to introduce the gene encoding nitrate reductase into a nit1 mutant strain which lacks nitrate reductase activity. By using either supercoiled or linear plasmid DNA, transformants were recovered consistently at a low efficiency, on the order of 15 transformants per microgram of plasmid DNA. In all cases the transforming DNA was integrated into the nuclear genome, usually in multiple copies. Most of the introduced copies were genetically linked to each other, and they were unlinked to the original nit1 locus. The transforming DNA and nit+ phenotype were stable through mitosis and meiosis, even in the absence of selection. nit1 transcripts of various sizes were expressed at levels equal to or greater than those in wild-type nit+ strains. In most transformants, nitrate reductase enzyme activity was expressed at approximately wild-type levels. In all transformants, nit1 mRNA and nitrate reductase enzyme activity were repressed in cells grown on ammonium medium, showing that expression of the integrated nit1 genes was regulated normally. When a second plasmid with a nonselectable gene was bombarded into the cells along with the nit1 gene, transformants carrying DNA from both plasmids were recovered. In some cases, expression of the unselected gene could be detected. With the advent of nuclear transformation in Chlamydomonas, it becomes the first photosynthetic organism in which both the nuclear and chloroplast compartments can be transformed. PMID- 2592400 TI - Identification of a human protein that interacts with nuclear localization signals. AB - Through a series of label transfer experiments, we have identified a HeLa cell nuclear protein that interacts with nuclear localization signals (NLSs). The protein has a molecular weight of 66,000 and an isoelectric point of approximately 6. It associates with a synthetic peptide that contains the SV-40 T antigen NLS peptide but not with an analogous peptide in which an asparagine is substituted for an essential lysine (un-NLS peptide). In addition to these peptides, several proteins have been tested as label donors. With the proteins, there is a correlation between nuclear localization (assayed with lysolecithin permeabilized cells) and label transfer to the 66-kD protein. The NLS peptide (but not the un-NLS peptide) competes with the proteins in label transfer experiments, but neither wheat germ agglutinin nor ATP has an effect. These results suggest that the 66-kD protein functions as an NLS receptor in the first step of nuclear localization. In the course of this work, we have observed that the Staphylococcus aureus protein A is a strongly karyophilic protein. Its dramatic nuclear localization properties suggest that it may have multiple copies of an NLS. PMID- 2592401 TI - Carboxy-terminal SEKDEL sequences retard but do not retain two secretory proteins in the endoplasmic reticulum. AB - The sequence Ser-Glu-Lys-Asp-Glu-Leu (SEKDEL) has been shown to be a signal which leads to retention of at least two proteins in the endoplasmic reticulum of animal cells (Munro and Pelham, 1987). In this study we tested the function of this signal by appending it to two secretory proteins, rat growth hormone and the alpha subunit of human chorionic gonadotrophin (hCG-alpha). We used oligonucleotide-directed mutagenesis and expression to generate proteins with SEKDEL added to the exact COOH termini and then carried out a detailed analysis of their transport in monkey COS cells. We found that transport was not blocked for either protein, but rather that the half-time for secretion was increased about sixfold for both proteins. Analysis of oligosaccharide processing on hCG alpha-SEKDEL and indirect immunofluorescence microscopy on cells expressing both proteins was consistent with a retardation of transport between the endoplasmic reticulum and the Golgi apparatus. A change in the last amino acid of the SEKDEL sequence from Leu to Val abolished the retardation almost completely, suggesting a highly specific interaction of the sequence with a receptor. A change in the first amino acid had little or no effect on retardation. We conclude that the SEKDEL signal can have strong effects on reducing the rate of protein exit from the endoplasmic reticulum without generating absolute retention. Presumably other features of protein structure must be important to generate absolute retention. PMID- 2592402 TI - A quantitative analysis of the endocytic pathway in baby hamster kidney cells. AB - A morphological analysis of the compartments of the endocytic pathway in baby hamster kidney (BHK) cells has been made using the fluid-phase marker horseradish peroxidase (HRP). The endocytic structures labeled after increasing times of endocytosis have been identified and their volume and surface densities measured. In the first 2 min of HRP uptake the volume density of the labeled structures increased rapidly and thereafter remained constant for the next 13-18 min. This plateau represents the volume density of endosome organelles and accounts for 0.65% of the cytoplasmic volume (or 6.8 microns 3 per cell). The labeled structures consist of tubular-cisternal elements which are frequently observed in continuity with 300-400 nm vesicles. After 15-20 min of internalization the volume density of HRP-labeled structures again increased rapidly and reached a second plateau between 30 and 60 min of labeling. This second increase corresponded to detectable levels of HRP reaching later, acid phosphatase (AcPase)-reactive compartments. These structures, comprising the prelysosomes and lysosomes, were mostly vesicular and collectively accounted for 3.5% of the cytoplasmic volume (or 37 microns 3 per cell). The absolute peripheral surface areas of the two classes of organelles (endosomes and prelysosomes/lysosomes) were estimated to be 430 and 370 microns 2 per cell, respectively. The volume of fluid internalized in the first 2 min of uptake was five- to sevenfold less than the volume of the compartment labeled in this time. To account for these results we propose that, after uptake from the cell surface, HRP is delivered to, and diluted in, endosomes that are preexisting organelles initially devoid of the marker. With increasing times of endocytosis the concentration of HRP in the early endosomes increases, as more of the marker enters this compartment. An elevation in HRP concentration in endosomes during the early time points was shown directly using anti-HRP antibodies and colloidal gold on cryosections. The stereological values given in the present study, in combination with earlier studies, provide a minimum estimate for both the total surface area of membranes and the rate of membrane synthesis in a BHK cell. PMID- 2592403 TI - Ligand-mediated internalization, recycling, and downregulation of the epidermal growth factor receptor in vivo. AB - EGF receptor internalization, recycling,a nd downregulation were evaluated in liver parenchyma as a function of increasing doses of injected EGF. The effect of ligand occupancy in vivo on the kinetics and extent of internalization was studied with changes in the receptor content of isolated plasmalemma and endosome fractions evaluated by direct binding, Scatchard analysis, and Western blotting. For all doses of injected EGF, receptor was lost from the plasmalemma and accumulated in endosomes in a time- and dose-dependent fashion. However, at doses of injected EGF equivalent to less than or equal to 50% surface receptor occupancy (i.e., less than or equal to 1 microgram/100 g body weight), receptor levels returned by 120 min to initial values. This return was resistant to cycloheximide and therefore did not represent newly synthesized receptor. Neither was the return due to replenishment by an intracellular pool of low-affinity receptors as such a pool could not be detected by Scatchard analysis or Western blotting. Therefore, receptor return was due to the recycling of previously internalized receptor. At doses of injected EGF greater than 50% receptor occupancy, net receptor loss-i.e., downregulation-was observed by evaluating the receptor content of total particulate fractions of liver homogenates. At the higher saturating doses of injected EGF (5 and 10 micrograms/100 g body weight), the majority of surface receptor content was lost by 15 min and remained low for at least an additional 105 min. As the kinetics of ligand clearance from the circulation and liver parenchyma were similar for all doses of EGF injected, then the ligand-mediated regulation of surface receptor content and downregulation were not a result of a prolonged temporal interaction of ligand with receptor. Rather, the phenomena must be a consequence of the absolute concentrations of EGF interacting with receptor at the cell surface and/or in endosomes. PMID- 2592404 TI - Ligand-mediated autophosphorylation activity of the epidermal growth factor receptor during internalization. AB - The association of EGF with its receptor in endosomes isolated from rat liver homogenates was assessed biochemically by polyethylene glycol precipitation and morphologically by electron microscope radioautography. The proportion of receptor-bound ligand in endosomes at 15 min after the injection of doses of 0.1 and 1 microgram EGF/100 g body weight was 57%. This value increased to 77% for the dose of 10 micrograms EGF injected. Quantitative electron microscope radioautography carried out on endosomes isolated at 15 min after the injection of 10 micrograms 125I-EGF demonstrated that most radiolabel was over the endosomal periphery thereby indicating that ligand-receptor complexes were in the bounding membrane but not in intraluminal vesicles of the content. EGF receptor autophosphorylation activity during internalization was evaluated in plasmalemma and endosome fractions. This activity was markedly but transiently reduced on the cell surface shortly after the administration of saturating doses of EGF. The same activity, however, was augmented and prolonged in endosomes for up to 30 min after EGF injection. The transient desensitization of cell surface activity was not due to prior in vivo phosphorylation since receptor dephosphorylation in vitro failed to restore autophosphorylation activity. Transient desensitization of cell surface autophosphorylation activity coincided with a diminished capacity for endocytosis of 125I-EGF with endocytosis returning to normal after the restoration of cell surface autophosphorylation activity. The inhibition of cell surface autophosphorylation activity and the activation of endosomal autophosphorylation activity coincident with downregulation suggest that EGF receptor traffic is governed by ligand-regulated phosphorylation activity. PMID- 2592405 TI - Developing Dictyostelium cells contain the lysosomal enzyme alpha-mannosidase in a secretory granule. AB - The prespore vesicle (PSV) is an organelle which secretes spore coat proteins and gal/galNAc polysaccharides from prespore cells of Dictyostelium. By combining the techniques of protein A-gold immunocytochemistry and ricin-gold affinity cytochemistry we have demonstrated colocalization of the lysosomal enzyme alpha mannosidase with gal/galNAc polysaccharides in prespore vesicles and the spore coat. To determine the origin of prespore vesicles a series of pulse-chase experiments were performed. Cells were labeled with [35S]methionine or [35S]sulfate at different times during development and allowed to differentiate in the presence of unlabeled methionine or sulfate for various periods of time. The cells were homogenized and intracellular organelles were separated using Percoll density gradient centrifugation. The distribution of [35S]methionine labeled alpha-mannosidase and [35S]sulfate-labeled glycoproteins in the Percoll gradients was determined. It was found that prespore vesicles contained protein which was previously found in lysosomes. Newly labeled protein also entered these vesicles. The data suggest that developing Dictyostelium cells either restructure preexisting lysosomes into prespore vesicles or transport protein between these two organelles. We propose that secretory granules and lysosomes may have a common biosynthetic origin and may be evolutionarily related. PMID- 2592406 TI - The subcellular organization of Madin-Darby canine kidney cells during the formation of a polarized epithelium. AB - Studies of the developing trophectoderm in the mouse embryo have shown that extensive cellular remodeling occurs during epithelial formation. In this investigation, confocal immunofluorescence microscopy is used to examine the three-dimensional changes in cellular architecture that take place during the polarization of a terminally differentiated epithelial cell line. Madin-Darby canine kidney cells were plated at a low density on permeable filter supports. Antibodies that specifically recognize components of the tight junction, adherens junction, microtubules, centrosomes, and the Golgi complex were used to study the spatial remodeling of the cytoarchitecture during the formation of the polarized cell layer. The immunofluorescence data were correlated with establishment of functional tight junctions as measured by transepithelial resistance and back exchange of the cell surface, labeled with metabolites of the fluorescent lipid analogue N-(7-[4-nitrobenzo-2-oxa-1,3-diazole]) aminocaproyl sphingosine. 1 d after plating, single cells had microtubules, radiating from a broad region, that contained the centrosomes and the Golgi complex. 2 d after plating, the cells had grown to confluence and had formed functional tight junctions close to the substratum. The centrioles had split and no longer organized the microtubules which were running above and below the nucleus. The Golgi complex had spread around the nucleus. By the fifth day after plating, the final polarized state had been achieved. The junctional complex had moved greater than 10 microns upward from its basal location. The centrioles were together below the apical membrane, and the Golgi complex formed a ribbon-like convoluted structure located in the apical region above the nucleus. The microtubules were organized in an apical web and in longitudinal microtubule bundles in the apical-basal axis of the columnar cell. The longitudinal microtubules were arranged with their minus ends spread over the apical region of the cell and their plus ends toward the basal region. These findings show that there is an extensive remodeling of epithelial cytoarchitecture after formation of cell-cell contacts. Reorganization of the microtubule network results in functional polarization of the cytoplasm. PMID- 2592408 TI - The structure of the cuticular plate, an in vivo actin gel. AB - The cuticular plate is a network of actin filaments found in hair cells of the cochlea. In the alligator lizard, it consists of rootlets, emanating from the stereocilia, and of cross-connecting actin filaments that anchor these rootlets. In thin sections, this network displays striking patches of 650 +/- 110-A striae. By quantitative analyses of the images, the mystery of the striae can be explained. They are due in part to the rootlets which are sets of flat ribbons of actin filaments. The ribbons in each set are separated by approximately 650 A. Numerous whiskers 30 A in diameter extend from each ribbon's face, interconnecting adjacent ribbons. The nonrootlet filaments, except at the margins of the cell, occur primarily as single filaments. Like the ribbons, they are bristling with whiskers. The patches of striae are explained by ribbons and filaments held at a 650-A separation by the whiskers that project from them. A simple model for regions of bewhiskered filaments is a box crammed full of randomly oriented test-tube brushes. A thin slice through the box will show regions of dark lines or striae due to the wire backbones of the brushes separated from one another by the bristle length. Using the computer instead of test-tube brushes, we have been able to model quantitatively the filament distribution and pattern of striae seen in the cuticular plate of the lizard. The organization of actin filaments we have deduced from our simulations differs from that found in macrophages or in the terminal web of intestinal epithelial cells. PMID- 2592407 TI - Evidence for a direct, nucleotide-sensitive interaction between actin and liver cell membranes. AB - We have investigated the association of actin with membranes isolated from rat liver. A plasma membrane-enriched fraction prepared by homogenization in a low salt/CaCl2 buffer was found to contain a substantial amount of residual actin which could be removed by treatment with 1 M Na2CO3/NaHCO3, pH 10.5. Using a sedimentation binding assay that uses gelsolin to shorten actin filaments and render membrane binding saturable (Schwartz, M. A., and E. J. Luna. 1986. J. Cell Biol. 102:2067-2075), we found that membranes stripped of endogenous actin bound 125I-actin in a specific and saturable manner. Scatchard plots of binding data were linear, indicating a single class of binding sites with a Kd of 1.6 microns; 66 micrograms actin bound/mg membrane protein at saturation. Binding of actin to liver cell membranes was negligible with unstripped membranes, was competed by excess unlabeled actin, and was greatly reduced by preheating or proteolytic digestion of the membranes. Kinetic measurements showed that binding had an initial lag phase and was strongly temperature dependent. The binding of actin to liver cell membranes was also found to be competitively inhibited by ATP and other nucleotides, including the nonhydrolyzable analogue AMP-PNP. We conclude that we have reconstituted an interaction between actin and integral membrane proteins from the rat liver. This interaction exhibits a number of distinctive features which have not been observed in other actin-membrane systems. PMID- 2592409 TI - Mass isolation of calf thymus centrosomes: identification of a specific configuration. AB - Centrosomes from calf thymocytes were isolated using a simple preparative procedure that provides large yields of free organelles. A comparative study with centrosomes isolated from human cultured lymphoblasts has led to the discovery of important differences in the structure of the two isolates and in their capacity to nucleate microtubules from purified tubulin. The possibility that the centrosomal structure depends upon the growth state of cells is discussed. PMID- 2592411 TI - Gap junctional communication in the extraembryonic tissues of the gastrulating mouse embryo. AB - We characterized gap junctional communication in the extraembryonic tissues of the 7.5-d gastrulating mouse embryo. At this stage of development, the extraembryonic tissues form a large part of the conceptus, and link the embryo proper to the maternal tissue. Using Lucifer yellow injections, cells in most extraembryonic tissues were observed to be very well dye coupled, the only exception being the peripheral regions of the ectoplacental cone. Of particular interest was the fact that no dye coupling was detected between the three major extraembryonic tissues. Thus, the extraembryonic ectoderm (EEC), the extraembryonic endoderm (EEN), and the ectoplacental cone (EPC) corresponded to separate communication compartments, with the EPC being further subdivided into three compartments. Interestingly, the EEN was observed to exhibit a very low level of dye coupling with the adjacent visceral embryonic endoderm (EN), and consistent with the latter dye coupling results was the finding that the EEN was ionically coupled to the EN, but not with any other extraembryonic tissues. However, in the EPC, ionic coupling studies show that the central region was well coupled ionically to the EEC, but only weakly coupled to the peripheral EPC. These findings, in conjunction with our previous study (1988. J. Cell Biol. 107:241-255), demonstrate that the 7.5-d mouse conceptus is subdivided into at least nine major Lucifer yellow-delineated communication compartments, with ionic coupling across some of these compartments effectively unifying the embryo into two large domains corresponding to the embryo proper and the major extraembryonic tissues. PMID- 2592410 TI - Genetic and molecular analysis of a Caenorhabditis elegans beta-tubulin that conveys benzimidazole sensitivity. AB - Benzimidazole anti-microtubule drugs, such as benomyl, induce paralysis and slow the growth of the nematode Caenorhabditis elegans. We have identified 28 mutations in C. elegans that confer resistance to benzimidazoles. All resistant mutations map to a single locus, ben-1. Virtually all these mutations are genetically dominant. Molecular cloning and DNA sequence analysis established that ben-1 encodes a beta-tubulin. Some resistant mutants are completely deleted for the ben-1 gene. Since the deletion strains appear to be fully resistant to the drugs, the ben-1 product appears to be the only benzimidazole-sensitive beta tubulin in C. elegans. Furthermore, since animals lacking ben-1 are viable and coordinated, the ben-1 beta-tubulin appears to be nonessential for growth and movement. The ben-1 function is likely to be redundant in the nematode genome. PMID- 2592412 TI - Junctional communication is induced in migrating capillary endothelial cells. AB - Using an in vitro model in which a confluent monolayer of capillary endothelial cells is mechanically wounded, gap junction-mediated intercellular communication has been studied by loading the cells with the fluorescent dye, Lucifer Yellow. Approximately 40-50% of the cells in a nonwounded confluent monolayer were coupled in groups of four to five cells (basal level). Basal levels of communication were also observed in sparse and preconfluent cultures, but were reduced in postconfluent monolayers. 30 min after wounding, coupling was markedly reduced between cells lining the wound. Communication at the wound was partially reestablished by 2 h, exceeded basal levels after 6 h and reached a maximum after 24 h, at which stage approximately 90% of the cells were coupled in groups of six to seven cells. When the wound had closed (after 8 d), the increase in communication was no longer observed. Induction of wound-associated communication was unaffected by exposure of the cells to the DNA synthesis inhibitor mitomycin C, but was prevented by the protein synthesis inhibitor, cycloheximide. The induction of wound-associated communication was also inhibited when migration was prevented by placing the cells immediately after wounding at 22 degrees C or after exposure to cytochalasin D, suggesting that the increase in communication is dependent on cells migrating into the wound area. In contrast, migration was not prevented when coupling was blocked by exposure of the cells to retinoic acid, although this agent did disrupt the characteristic sheet-like pattern of migration typically seen during endothelial repair. These results suggest that junctional communication may play an important role in wound repair, possibly by coordinating capillary endothelial cell migration. PMID- 2592414 TI - Neurite extension and neuronal survival activities of recombinant S100 beta proteins that differ in the content and position of cysteine residues. AB - S100 beta produced in Escherichia coli from a synthetic gene (Van Eldik, L. J., J. L. Staecker, and F. Winningham-Major. 1988. J. Biol. Chem. 263:7830-7837) stimulates neurite outgrowth and enhances cell maintenance in cultures of embryonic chick cerebral cortex neurons. In control experiments, the neurite extension activity is reduced by preincubation with antibodies made against bovine brain S100 beta. When either of the two cysteines in S100 beta are altered by site-directed mutagenesis, the resultant proteins maintain the overall biochemical properties of S100 beta, but lose both the neurite extension and neuronal survival activities. However, another S100 beta mutant, in which the relative position of one of the two cysteines was changed, had neurotrophic activity similar to that of the unmodified protein. These and other results indicate that (a) specific neurite extension activity and neuronal survival activity are two related activities inherent to the S100 beta molecule; (b) a disulfide-linked form of S100 beta is required for full biological activity, and (c) the relative position of the cysteines can be modified. These data suggest potential in vivo roles for S100 beta in the development and maintenance of neuronal function in the central nervous system, and demonstrate the feasibility of the longer term development of selective pharmacological agents based on the S100 beta structure. PMID- 2592413 TI - The identification of a novel synaptosomal-associated protein, SNAP-25, differentially expressed by neuronal subpopulations. AB - cDNA clones of a neuronal-specific mRNA encoding a novel 25-kD synaptosomal protein, SNAP-25, that is widely, but differentially expressed by diverse neuronal subpopulations of the mammalian nervous system have been isolated and characterized. The sequence of the SNAP-25 cDNA revealed a single open reading frame that encodes a primary translation product of 206 amino acids. Antisera elicited against a 12-amino acid peptide, corresponding to the carboxy-terminal residues of the predicted polypeptide sequence, recognized a single 25-kD protein that is associated with synaptosomal fractions of hippocampal preparations. The SNAP-25 polypeptide remains associated with synaptosomal membrane components after hypoosmotic lysis and is released by nonionic detergent but not high salt extraction. Although the SNAP-25 polypeptide lacks a hydrophobic stretch of residues compatible with a transmembrane region, the amino terminus may form an amphiphilic helix that may facilitate alignment with membranes. The predicted amino acid sequence also includes a cluster of four closely spaced cysteine residues, similar to the metal binding domains of some metalloproteins, suggesting that the SNAP-25 polypeptide may have the potential to coordinately bind metal ions. Consistent with the protein fractionation, light and electron microscopic immunocytochemistry indicated that SNAP-25 is located within the presynaptic terminals of hippocampal mossy fibers and the inner molecular layer of the dentate gyrus. The mRNA was found to be enriched within neurons of the neocortex, hippocampus, piriform cortex, anterior thalamic nuclei, pontine nuclei, and granule cells of the cerebellum. The distribution of the SNAP-25 mRNA and the association of the protein with presynaptic elements suggest that SNAP-25 may play an important role in the synaptic function of specific neuronal systems. PMID- 2592415 TI - The cytomechanics of axonal elongation and retraction. AB - Neurites of PC12 and chick dorsal root ganglion neurons behave as viscoelastic solids in response to applied forces. This passive behavior can be modeled with three mechanical elements; a relatively stiff, undamped spring in series with a Voight element composed of a less stiff spring in parallel with a dashpot. In response to applied tensions greater than 100 microdynes, PC12 cells show lengthening behavior distinct from and in addition to the passive viscoelastic response. We interpret this as "towed growth" (Bray, D. 1984. Dev. Biol. 102:379 389) because the neurites can become twice as long without obvious thinning of the neurite and because in two cases neurite tensions fell below original rest tensions, a result that cannot be obtained with passive viscoelastic elements. The rate of towed growth showed a linear dependence of growth rate with applied tensions in 8 of 12 PC12 neurites exposed to applied tension greater than 100 microdynes. Both PC12 and chick sensory neurons showed evidence of retraction when neurite tensions were suddenly diminished. This response was measured as tension recovery after slackening in chick sensory neurites. In 62% of the cases, tension recovery exceeded and sometimes doubled the preexperimental steady-state tension. Our data indicate that this response is active tension generation by the neurite shaft. We conclude that neurite length is regulated by axial tension in both elongation and retraction. Our data suggest a three-way controller: above some tension set point, the neurite is stimulated to elongate. Below some different, lower tension threshold the neurite is stimulated to retract. Between these two tension thresholds, the neurite responds passively as a viscoelastic solid. PMID- 2592416 TI - Changes in microtubule polarity orientation during the development of hippocampal neurons in culture. AB - Microtubules in the dendrites of cultured hippocampal neurons are of nonuniform polarity orientation. About half of the microtubules have their plus ends oriented distal to the cell body, and the other half have their minus ends distal; in contrast, microtubules in the axon are of uniform polarity orientation, all having their plus ends distal (Baas, P.W., J.S. Deitch, M. M. Black, and G. A. Banker. 1988. Proc. Natl. Acad. Sci. USA. 85:8335-8339). Here we describe the developmental changes that give rise to the distinct microtubule patterns of axons and dendrites. Cultured hippocampal neurons initially extend several short processes, any one of which can apparently become the axon (Dotti, C. G., and G. A. Banker. 1987. Nature [Lond.]. 330:477-479). A few days after the axon has begun its rapid growth, the remaining processes differentiate into dendrites (Dotti, C. G., C. A. Sullivan, and G. A. Banker. 1988. J. Neurosci. 8:1454-1468). The polarity orientation of the microtubules in all of the initial processes is uniform, with plus ends distal to the cell body, even through most of these processes will become dendrites. This uniform microtubule polarity orientation is maintained in the axon at all stages of its growth. The polarity orientation of the microtubules in the other processes remains uniform until they begin to grow and acquire the morphological characteristics of dendrites. It is during this period that microtubules with minus ends distal to the cell body first appear in these processes. The proportion of minus end-distal microtubules gradually increases until, by 7 d in culture, about equal numbers of dendritic microtubules are oriented in each direction. Thus, the establishment of regional differences in microtubule polarity orientation occurs after the initial polarization of the neuron and is temporally correlated with the differentiation of the dendrites. PMID- 2592417 TI - Antibodies to the L1 adhesion molecule inhibit Schwann cell ensheathment of neurons in vitro. AB - To investigate whether neural adhesion molecules are involved in neuron-induced Schwann cell differentiation, cocultures of pure dorsal root ganglion neurons, and Schwann cells were maintained in the presence of antibodies to evaluate possible perturbing effects. Several parameters characteristic of differentiating Schwann cells were studied, such as transition of spindle-shaped to flattened, i.e., more epithelioid morphology, association with neuronal cell bodies, ensheathment of neurites, production of basal lamina and collagen fibrils, and expression of the myelin associated glycoprotein (MAG). A complete ablation of Schwann cell differentiation in all features studied was seen with antibodies to the neural adhesion molecule L1. Antibodies to N-CAM did not reduce the association of Schwann cells with neurites but abolished the interdigitation of Schwann cell processes into neurite bundles, while leaving the other parameters studied unaffected. Fab fragments of antibodies to J1, MAG, and mouse liver membranes did not interfere with the manifestation of any of these parameters. None of the antibodies changed incorporation of [3H]thymidine into Schwann cells. PMID- 2592418 TI - Differential effects of heparin, fibronectin, and laminin on the phosphorylation of basic fibroblast growth factor by protein kinase C and the catalytic subunit of protein kinase A. AB - Basic fibroblast growth factor (FGF) is synthesized as a phosphoprotein by both bovine capillary endothelial and human hepatoma cells in culture. Because basic FGF is characterized by its high affinity for heparin and its association in vivo with the extracellular matrix, we examined the possibility that the phosphorylation of this growth factor by purified protein kinase C (PK-C) and the catalytic subunit of cAMP-dependent protein kinase-A (PK-A) can be modulated by components of the extracellular matrix. Heparin and other glycosaminoglycans (GAGs) inhibit the ability of PK-C to phosphorylate basic FGF. In contrast, heparin can directly increase the phosphorylation of basic FGF by PK-A. While fibronectin, laminin, and collagen IV have no effect on the ability of PK-C to phosphorylate basic FGF, they all can inhibit the effects of PK-A. Thus, there is a differential effect of extracellular matrix-derived proteins and GAGs on the phosphorylation of basic FGF. The enhanced phosphorylation of basic FGF that is mediated by heparin is associated with a change in the kinetics of the reaction and the identity of the amino acid targeted by this enzyme. The amino acids that are targeted by PK-C and PK-A have been identified by phosphopeptide analyses as Ser64 and Thr112, respectively. In the presence of heparin, basic FGF is no longer phosphorylated by PK-A at the usual PK-A consensus site (Thr112), but instead is phosphorylated at the canonical PK-C site (Ser64). Accordingly, heparin inhibits the phosphorylation of basic FGF by PK-C presumably by masking the PK-C dependent consensus sequence surrounding Ser64. Thus, when basic FGF is no longer phosphorylated by PK-A in the receptor binding domain (Thr112), it loses the increased receptor binding ability that characterizes PK-A phosphorylated basic FGF. The results presented here demonstrate three novel features of basic FGF. First, they identify a functional effect of the binding of heparin to basic FGF. Second, they establish that the binding of heparin to basic FGF can induce structural changes that alter the substrate specificity of protein kinases. Third, and perhaps most important, the results demonstrate the existence of a novel interaction between basic FGF, fibronectin, and laminin. Although the physiological significance of this phosphorylation is not known, these results clearly suggest that the biological activities of basic FGF are regulated by a complex array of biochemical interactions with the proteins, proteoglycans, and glycosaminoglycans present in the extracellular milieu and the cytoplasm. PMID- 2592419 TI - Membrane-anchored and soluble forms of betaglycan, a polymorphic proteoglycan that binds transforming growth factor-beta. AB - Transforming growth factors beta 1 and beta 2 bind with high affinity to the core protein of a 250-350-kD cell surface proteoglycan. This proteoglycan (formerly referred to as the type III TGF-beta receptor) coexists in many cells with the receptor implicated in TGF-beta signal transduction (type I TGF-beta receptor), but its function is not known. We report here that soluble TGF-beta-binding proteoglycans are released by several cell types into the culture media, and can be found in serum and extracellular matrices. As has been shown for the membrane bound form, the soluble proteoglycans have a heterogeneous core protein of 100 120 kD that carries chondroitin sulfate and/or heparan sulfate glycosaminoglycan chains and a small amount of N-linked carbohydrate. The membrane-bound form of this proteoglycan is hydrophobic and associates with liposomes, whereas the soluble forms lack a membrane anchor and do not associate with liposomes. Differences in the electrophoretic migration of the soluble and membrane forms of this proteoglycan suggest additional structural differences in their core proteins and glycosaminoglycan chains. These soluble and membrane-bound proteoglycans, for which we propose the name "betaglycans," might play distinct roles in pericellular retention, delivery, or clearance of activated TGF-beta. PMID- 2592421 TI - Regulation of bone sialoprotein mRNA by steroid hormones. AB - In this report we demonstrate an increase in the steady-state level of bone sialoprotein (BSP) mRNA in rat calvaria and a rat osteosarcoma cell line (ROS 17/2.8) after treatment with the synthetic glucocorticoid, dexamethasone. In contrast, 1.25-dihydroxyvitamin D3 reduced the amount of BSP mRNA in calvaria and inhibited the dexamethasone induction in ROS 17/2.8 cells. The increase in BSP mRNA is most likely due to an increase in the transcriptional rate. The stability of mRNA was unchanged after dexamethasone treatment with a half-life of approximately 5 h. Nuclear transcription experiments with nuclei isolated from ROS 17/2.8 cells showed an increased BSP mRNA synthesis in cells treated with dexamethasone. PMID- 2592420 TI - Heparin selectively inhibits a protein kinase C-dependent mechanism of cell cycle progression in calf aortic smooth muscle cells. AB - The proliferation of arterial smooth muscle cells (SMCs) plays a critical role in the pathogenesis of arteriosclerosis. Previous studies have indicated that the glycosaminoglycan heparin specifically inhibited the growth of vascular SMCs in vivo and in culture, although the precise mechanism(s) of action have not been elucidated. In this study, we have examined the ability of specific mitogens (PDGF, EGF, heparin-binding growth factors, phorbol esters, and insulin) to stimulate SMC proliferation. Our results indicate that SMCs derived from different species and vascular sources respond differently to these growth factors. We next examined the ability of heparin to inhibit the proliferative responses to these mitogens. In calf aortic SMCs, heparin inhibits a protein kinase C-dependent pathway for mitogenesis. Detailed cell cycle analysis revealed several new features of the effects of heparin on SMCs. For example, heparin has two effects on the Go----S transition: it delays entry into S phase and also reduces the number of cells entering the cycle from Go. Using two separate experimental approaches, we found that heparin must be present during the last 4 h before S phase, suggesting a mid-to-late G1 heparin block. In addition, our data indicate that heparin-treated SMCs, while initially blocked in mid-to-late G1, slowly move back into a quiescent growth state in the continued presence of heparin. These results suggest that heparin may have multiple targets for its antiproliferative effect. PMID- 2592422 TI - Immunological characterization of a basement membrane-specific chondroitin sulfate proteoglycan. AB - Reichert's membrane, an extraembryonic membrane present in developing rodents, has been proposed as an in vivo model for the study of basement membranes. We have used this membrane as a source for isolation of basement membrane proteoglycans. Reichert's membranes were extracted in a guanidine/3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonate buffer followed by cesium chloride density-gradient ultracentrifugation under dissociative conditions. The proteoglycans were subsequently purified from the two most dense fractions (greater than 1.3 g/ml) by ion-exchange chromatography. Mice were immunized with the proteoglycan preparation and four mAbs recognizing the core protein of a high density, buoyant chondroitin sulfate proteoglycan were raised. Confirmation of antibody specificity was carried out by the preparation of affinity columns made from each of the mAbs. Chondroitin sulfate proteoglycans (CSPGs) were purified from both supernatant and tissue fractions of Reichert's membranes incubated in short-term organ culture in the presence of radiolabel. The resultant affinity purified proteoglycan samples were examined by gel filtration, SDS-PAGE, and immunoblotting. This proteoglycan is of high molecular weight (Mr = 5-6 x 10(5)), with a core protein of Mr = approximately 1.5-1.6 x 10(5) and composed exclusively of chondroitin sulfate chains with an average Mr = 1.6-1.8 x 10(4). In addition, a CSPG was purified from adult rat kidney, whose core protein was also Mr = 1.6 x 10(5). The proteoglycan and its core protein were also recognized by all four mAbs. Indirect immunofluorescence of rat tissue sections stained with these antibodies reveal a widespread distribution of this proteoglycan, localized specifically to Reichert's membrane and nearly all basement membranes of rat tissues. In addition to heparan sulfate proteoglycans, it therefore appears that at least one CSPG is a widespread basement membrane component. PMID- 2592424 TI - Differential response among cells in the chick embryo myogenic lineage to photosensitization by Merocyanine 540. AB - Primary cultures of myogenic cells from progressively older embryonic and adult chickens were incubated in medium containing Merocyanine 540 (MC540) and were exposed to white light during the incubation period. After exposure, the cultures were followed to determine cell survival and differentiation. MC540 attached to the surface membranes of all cells. In cultures from 10-day embryos (E10 cells), concentrations of MC540 greater than or equal to 60 micrograms/ml resulted in death of nearly all myogenic cells upon exposure to light, but non-myogenic cells survived and replicated. Below 60 micrograms/ml, there was a dose-dependent reduction in muscle differentiation. At concentrations less than 40 micrograms/ml, there was no effect on myogenesis. Cultures of cells from 18-day (E18) embryos (myogenic stem cells) and from adult muscle (satellite cells) were resistant to doses of MC540 that killed E10 cells. E14 myogenic cell populations contained both resistant and sensitive sub-populations. Terminally differentiated muscle cells were more sensitive to MC540 than precursor cells from any age embryo. Progeny of E18 cells acquired sensitivity to MC540 as differentiation proceeded. In clonal cultures, cells that normally give rise to small muscle clones (committed cells) were selectively destroyed by exposure to the dye. These observations demonstrate that an MC540-resistant myogenic population is present in low numbers in 10-day embryonic pectoral muscle. As development proceeds, this population increases such that, by 18 days of gestation, most of the myogenic cells are resistant to MC540. The results also suggest that embryonic chick myogenic stem cells and adult satellite cells have surface membrane properties which differ from those of their committed progeny. PMID- 2592423 TI - Calcium-independent growth of human ovarian carcinoma cells. AB - Evidence in the literature suggests that cancer cell growth in vitro is generally not sensitive to external calcium. A human ovarian carcinoma cell line (SKOV3) retained 60% of its normal growth in Dulbecco modified Eagle's medium (DME) when the calcium concentration was reduced from 3 mM to 10 microM. Chinese hamster ovary cells (CHO) were growth-arrested in media containing less than 500 microM calcium. In low-calcium (10 microM) DME, 10 microM of a calmodulin antagonist W7 inhibited the growth of SKOV3 cells by more than 90%, while 100 microM of its inactive analog W5 was mildly inhibitory (20%). The growth inhibition by W7 was antagonized by increasing calcium concentrations in the culture media, while the inhibition by W5 was calcium-independent. The phorbol ester TPA was also effective in antagonizing W7's growth inhibition in low-calcium DME, suggesting that the W7 effect is mediated via protein kinase C inhibition. SKOV3 total cellular protein kinase C activity was 1.6 times higher than CHO cells when incubated in normal DME. When incubated in low-calcium DME, a large drop in protein kinase C activity in the CHO cells was observed while the enzyme activity was unchanged in the SKOV3 cells. Our data suggest that these human ovarian tumor cells have altered cellular calcium regulatory processes associated with the defective down-regulation of protein kinase C. This defect may confer these cells the ability to proliferate independently of the external calcium concentration. Targeting the cellular signal transduction components may be useful in cancer chemotherapy. PMID- 2592425 TI - Different pattern of differentiation in two LLC-PK1 clones. AB - Two clones (LD3 and LC3) were isolated from the established renal cell line LLC PK1. They differed with respect to the development of the Na+-dependent alpha methyl-D-glucoside (AMG) uptake. The higher uptake capacity in LD3 as compared to LC3 was owing to the expression of a higher number of carrier molecules as was shown by the specific phlorizin binding. The intracellular cyclic AMP level, the D-glucose concentration in the growth medium and the cell density could be excluded as the causes of the difference between both clones. We found that the faster development of the Na+-dependent hexose carrier in LD3 was parallelled by a faster expression of trehalase in this clone. This suggests that the expression of both apical proteins is correlated. From the growth curves it was concluded that renewal of the undifferentiated population was roughly the same in both clones. The recruitment of cells from the undifferentiated to the growth arrested state seems also very similar as was deduced from the development of tight junctions and from the down-regulation of the alpha-methylaminoisobutyric acid (meAIB) uptake. The start of differentiation was identical as was shown by the similar rate of expression found for gamma-glutamyl transferase. The difference between both clones is most likely situated at the traverse to a fully differentiated cell. This process takes more time in LC3 than in LD3. Also the fully differentiated state seemed to be different in both clones. We conclude that the pattern of differentiated characteristics found in both clones is different and a model incorporating these differences is presented. PMID- 2592426 TI - Heat protectors and heat-induced preferential redistribution of 26 and 70 kDa proteins in Chinese hamster ovary cells. AB - An overall increase of 40% in nuclear-associated protein has been shown to be one of the sequellae of exposure of eukaryotic cells to elevated temperatures. Several investigators have shown that the increased protein/DNA ratios correlated well with the degree of cytotoxicity. In previous investigations, we have shown that cycloheximide, which protects the cell from the killing effects of heat, produces a dramatic reduction of the bulk nuclear-associated proteins after heating. In this investigation, we studied a previously unobserved efflux of a 26 kDa protein after heat shock and the preferential accumulation of the 70 kDa protein. The 26 kDa protein was shown not to be a member of previously described heat shock protein families. Preferential reduction of a 26 kDa protein and accumulation of a 70 kDa protein was observed in nuclei isolated from Chinese hamster ovary cells after heating at 43 degrees C. After heat treatment, the 26 kDa protein in the nucleus was decreased to a level 0.1-0.3 times the original amount in unheated cells, and the 70 kDa protein in the nucleus increased by a factor of 1.6-1.8. The normal levels of these two proteins were restored when cells were incubated at 37 degrees C following heat shock. Cells treated with heat protectors, cycloheximide and histidinol, demonstrated approximately the same redistribution in nuclear 26 and 70 kDa proteins immediately after heating as those not exposed to these drugs. On the other hand, restoration to control levels was much faster in the protector-treated cells, suggesting that "repair" of heat-induced damage is an important factor in the cells ability to survive this insult. Return to normal protein levels did not require new protein synthesis. PMID- 2592427 TI - Multiple sequential periods of DNA synthesis and quiescence in primary hepatocyte cultures maintained on the DMSO-EGF on/off protocol. AB - Repeated periods of DNA synthesis activity (each period consisting of two to three cycles) separated by intervals of quiescence in primary rat hepatocytes can be stimulated by sequential addition and removal of 2% dimethyl sulfoxide (DMSO) in the presence of epidermal growth factor (EGF). Hepatocytes can be kept in nonproliferating cultures for 7 days in media supplemented with 2% DMSO and EGF. If DMSO is removed while EGF is maintained, rat and human hepatocytes enter a 3 to 4 day period of DNA synthesis that declines rapidly by days 4 and 5. If DMSO is reintroduced into cultures at that point, kept on for 3 more days and removed again, hepatocytes reenter into proliferation with another self-limited response of 3 to 4 days. Similar phenomena can seen with hepatocytes maintained in the presence of 3 mM phenobarbital. These protocols demonstrate that loss of responsiveness to mitogens in primary hepatocyte cultures is not an irreversible process. They also raise the possibility that signals for termination of DNA synthesis in hepatocytes emanate from hepatocytes themselves. These studies also suggest for the first time the possibility of designing in vitro systems that will allow clonal expansion of differential hepatocytes. PMID- 2592428 TI - Hemin enhances differentiation and maturation of cultured regenerated skeletal myotubes. AB - Satellite cells, isolated from marcaine-damaged rat skeletal muscle, differentiate in culture to form contracting, cross-striated myotubes. Addition of 20 microM hemin (ferriprotoporphyrin IX chloride) to the culture medium resulted in increases in the number, size, and alignment of myotubes; in the number of myotubes that exhibited cross-striations; and in the strength and frequency of myotube contractions. Hemin increased satellite cell fusion by 27%, but decreased cell proliferative rate by 30%. Hemin increased the specific activity of creatine kinase (CK), a sensitive indicator of muscle differentiation, by 157%. Separation of CK isoenzymes by agarose gel electrophoresis showed that hemin increased only the muscle-specific CK isoenzymes (MM-CK and MB-CK). Thus, hemin seems to duplicate some of the effects of innervation on cultured myotubes by increasing contraction frequency and strength, appearance of cross-striations, and muscle-specific isoenzymes. In contrast, 3-amino-1,2,4-triazole, an inhibitor of heme biosynthesis, decreased the number of cross-striated myotubes, the strength and frequency of myotube contractions, and CK activity. These inhibitory effects were reversed by hemin. Collectively, these results demonstrate a physiologically significant role for heme in myotube maturation. PMID- 2592429 TI - Receptor specific for certain nucleotides stimulates inositol phosphate metabolism and Ca2+ fluxes in A431 cells. AB - We have recently reported that extracellular ATP induces a transient rise in cytosolic free Ca2+ [( Ca2+]i) in individual human epidermoid carcinoma A431 cells (Gonzalez et al: Journal of Cellular Physiology 135:269-276, 1988). We have now studied nucleotide specificity and desensitization for several early responses. Extracellular ATP (5-100 microM) caused the rapid formation of inositol trisphosphate and later its metabolites, inositol bisphosphate and inositol monophosphate. ATP also induced the efflux of 45Ca2+ from pre-loaded cells. In addition, an increase in the rate of influx of 45Ca2+ stimulated by extracellular ATP was detected. Based on measurements of 45Ca2+ efflux and influx, desensitization studies, and chlortetracycline fluorimetry, we conclude that ATP mobilizes Ca2+ from internal stores and also stimulates entry across the plasma membrane. These effects were also displayed by UTP and to a lesser extent by ITP, while other nucleoside triphosphates as well as ADP, AMP, and adenosine, were inactive. Furthermore, desensitization of the response to ATP and UTP was seen after prolonged exposure to either nucleotide. This was specific for the nucleotide receptor since a response to bradykinin was not affected by the ATP pretreatment, although pretreatment with phorbol ester inhibited responses to both the nucleotides and bradykinin. Quantitative data on rate of recovery from the desensitized state and the response of desensitized cells to greatly elevated levels of ATP are presented. Extracellular ATP stimulated another early change previously reported for epidermal growth factor, namely, the phosphorylation of an 81-kDa cytoskeletal protein. The stimulation of these events involves an ATP receptor whose properties differ from other ATP receptors that have been described. PMID- 2592430 TI - Reversible forskolin-induced impairment of sucrase-isomaltase mRNA levels, biosynthesis, and transport to the brush border membrane in Caco-2 cells. AB - Hybridization analysis of mRNA with a cDNA probe for human sucrase-isomaltase, pulse-chase experiments with L-[35S]-methionine followed by SDS-PAGE, and immunofluorescence detection of sucrase-isomaltase were used to analyze the level(s) at which forskolin interferes with the expression of the enzyme in Caco 2 cells in culture. Three effects are observed in Caco-2 cells treated with forskolin: 1) a marked decrease in the level of sucrase-isomaltase mRNA, 2) a marked decrease in the biosynthesis of the enzyme without any alteration of its stability, and 3) an almost total inhibition of its transport to the brush border membrane. All three effects are reversible when the drug is removed from the culture medium, though this reversibility is asynchronous: transport to the brush border membrane resumes after 24 h, sucrase-isomaltase mRNA levels are back to the normal after 5 days, whereas the biosynthesis of the enzyme, although increasing progressively, remains lower than in control cells, even 10 days after removal of the drug. The possibility that some effects are directly dependent on cAMP and others a consequence of changes in glucose metabolism is discussed. PMID- 2592431 TI - Preparation and characterization of plasma membrane vesicles from human polymorphonuclear leukocytes. AB - It would be advantageous to prepare models of the neutrophil plasma membrane in order to examine the role of the plasma membrane in transmembrane signal transduction in the human neutrophil and to dissect ligand-receptor interactions and structural changes in the cell surface upon stimulation. A number of investigators have prepared neutrophil membrane vesicles by homogenization, sonication, or centrifugation--techniques that can result in the loss of substantial amounts of surface membrane material, disruption of lysosomes causing proteolysis of membrane proteins, and contamination of the plasma membrane fraction by internal membranes. These limitations have been overcome in the present studies by employing a modification of the method previously developed in this laboratory. Human neutrophils were suspended in a buffer simulating cytoplasmic ionic and osmotic conditions and disrupted by nitrogen cavitation. The resultant cavitate was freed of undisrupted cells and nuclei and then centrifuged through discontinuous isotonic/isoosmotic Percoll gradients, which resolved four fractions: alpha (intact azurophilic granules), beta (intact specific granules), gamma (membrane vesicles), and delta (cytosol). The gamma fraction was highly enriched in alkaline phosphatase, a marker of the plasma membrane. In addition, this fraction contained less than 5% of the amounts of lysosomes (indicated by lysozyme activity) and nuclei (indicated by DNA content) found in intact cells or in unfractionated cavitate. Furthermore, the gamma fraction contained less than 10% of the levels of endoplasmic reticulum, Golgi, mitochondrial, and lysosomal membranes in cells or cavitates, as determined by assays for glucose 6-phosphatase, galactosyl transferase, monoamine oxidase, and Mo1 (CD11b/CD18; Mac-1), respectively. Finally, 75% of the membrane vesicles were sealed, as indicated by assay of ouabain-sensitive (Na+,K+) ATPase activity, and 55% were oriented right-side-out, as determined by exposure of concanavalin A (ConA) receptors and sialic acid residues on the surfaces of the vesicles. These heterogeneous preparations could be enriched for right-side-out vesicles by their selective adherence to ConA-coated plates and subsequent detachment by rinsing the surfaces of the plates with alpha-methylmannoside. This enrichment protocol did not affect the integrity of the vesicles and resulted in populations in which greater than 85% of the vesicles were oriented right-side-out. This procedure thus permits the preparation of sealed, right-side-out membrane vesicles that may be used as valid experimental models of the neutrophil plasma membrane in a variety of functional studies. PMID- 2592432 TI - Characterization of neutral and cationic amino acid transport in Xenopus oocytes. AB - Amino acid transport was characterized in stage 6 Xenopus laevis oocytes. Most amino acids were taken up by the oocytes by way of both Na+-dependent and saturable Na+-independent processes. Na+-dependent transport of 2-aminoisobutyric acid (AIB) was insensitive to cis- or trans-inhibition by the System A-defining substrate 2-(methylamino)-isobutyric acid (MeAIB), although threonine, leucine, and histidine were found to be effective inhibitors, eliminating greater than 80% of Na+-dependent AIB uptake. Lack of inhibition by arginine eliminates possible mediation by System Bo,+ and suggests uptake by System ASC. The Na+-dependent transport of characteristic System ASC substrates such as alanine, serine, cysteine, and threonine was also insensitive to excess MeAIB. Evidence to support the presence of System Bo,+ was obtained through inhibition analysis of Na+ dependent arginine transport as well arginine inhibition of Na+-dependent threonine uptake. The Na+-independent transport of leucine was subject to trans stimulation and was inhibited by the presence of excess phenylalanine, histidine, and, to a lesser extent, 2-amino-(2,2,1)-bicycloheptane-2-carboxylic acid (BCH). These observations are consistent with mediation by System L. The characteristics of Na+-independent uptake of threonine are not consistent with assignment to System L, and appear to be reflective of Systems asc and bo,+. In its charged state, histidine appears to be transported by a carrier similar in its specificity to System y+, but is taken up by System L when present as a zwitterion. PMID- 2592433 TI - Secretory character of a group of isoproterenol-induced polypeptides in mouse parotid glands. AB - The secretory nature of the isoproterenol-induced mouse parotid polypeptides C, D, E, F, and G (molecular weights 64,000, 61,000, 51,500, 38,000, and 37,000, respectively) is documented. Polypeptides C, D, E, F, and G, accumulated in response to successive daily stimulations with isoproterenol, were detected in a fraction enriched in hypertrophic parotid acinar cells. These cells, characterized by an increased content of cytoplasmic granules, maintain a secretory responsiveness to isoproterenol, which has been evidenced by light microscopy, enzymatic analysis, and unidimensional SDS-polyacrylamide gel electrophoresis. Thus, a parallelism in the loss and recovery of both secretory granules, alpha-amylase and polypeptides C, D, E, F, and G, was observed. Moreover, after secretion stimulation, polypeptides C, D, E, F, and G were detected in the fluid collected directly from parotid gland cannulation. Given the secretory character of polypeptides C, D, E, F, and G, mechanisms explaining both their progressive accumulation along the chronic administration of isoproterenol, as well as their progressive disappearance observed after suspending that treatment, are discussed. PMID- 2592434 TI - Agarose-selected variants of two human tumor cell lines exhibit altered methionine auxotrophy. AB - Our aim was to determine if the selection of human tumor cells with enhanced anchorage-independent growth capacity was associated with alterations in methionine auxotrophy. Cells with an increased ability to form colonies on soft agarose were selected from human melanoma (MeWo) and neuroepithelioma (SK-N-MC) cell lines. In contrast to their respective parental lines, a high proportion of the agarose-selected variants were completely unable to proliferate in methionine free medium containing its immediate precursor homocysteine. The variants exhibited no significant change in their total DNA 5-methylcytosine content and showed no stimulation of either RNA or DNA synthesis upon the addition of homocysteine when the cells were cultured in methionine-free medium. These variants were unable to synthesize [3H]S-adenosylmethionine from [3H]adenine and homocysteine. The failure to detect the accumulation of [3H]S-adenosylmethionine in these variant lines was not likely due to the enhanced turnover of S adenosylmethionine but rather to a reduced ability to synthesize methionine from homocysteine and 5-methyltetrahydrofolic acid. These results support our hypothesis that alterations in the metabolism of methionine and/or intracellular transmethylating activities may contribute to, or be associated with, the autonomous growth of malignant human tumor cells. PMID- 2592435 TI - Synthesis and secretion of interphotoreceptor retinoid-binding protein (IRBP) by isolated normal and rd mouse retinal photoreceptor neurons in culture. AB - Cultures of dissociated retinal neurons and photoreceptors from homozygous wild type, heterozygous rd/+ and homozygous rd/rd retinas have been used to investigate the capacity of isolated photoreceptor cells to synthesize and secrete the interphotoreceptor retinoid-binding protein (IRBP). Retinal cells were dissociated on postnatal day 2 and grown in chemically defined medium in the absence of glial and pigmented epithelial cells. Expression of IRBP immunoreactive materials in these cultures was cell type-specific and developmentally regulated. Thus increasing numbers of rod photoreceptor cells showed immunoreactivity during the first week in culture, whereas nonphotoreceptor cell types remained consistently negative. Photoreceptor immunoreactivity could be detected in permeated (detergent-treated) as well as in unpermeated preparations, the latter suggesting that some IRBP is associated with the photoreceptor cell surface. These materials appeared to be loosely bound to the photoreceptors, since they disappeared when the cultures were exposed for 6 hr to IRBP-free medium but not when they were exposed to IRBP-containing medium. IRBP synthesis and secretion could be demonstrated by analyzing either cell extracts or conditioned medium by "slot blot" and Western blot techniques using affinity purified antibodies against bovine IRBP as well as by fluorographic analysis after metabolic labeling of the cultures with 35S-methionine. Comparisons of cultures from the different genotypes showed many similarities, including the abundance of IRBP-immunoreactive photoreceptors in 7 day cultures. However, immunochemical analysis showed lower conditioned medium/cell extract IRBP ratios in rd/rd cultures, an observation consistent with previous reports suggesting that IRBP secretion may be deficient in rd/rd photoreceptor cells. PMID- 2592437 TI - Processing of asparagine-linked oligosaccharides is an early biochemical marker of the enterocytic differentiation of HT-29 cells. AB - The inability of HT-29 cells to undergo an enterocytic differentiation when grown in a glucose-containing (Glc+) medium has been recently correlated to an overall impairment of N-glycan processing. These results were obtained using confluent HT 29 cells in which the differentiation characteristics are fully expressed under differentiation permissive conditions (glucose-deprived medium, Glc-). Whether these changes of N-glycan processing appear progressively during the cell growth or are already present from the beginning of the culture was investigated in this work by comparing the actual status of N-glycan processing in both exponentially growing Glc+ and Glc- HT-29 cells. Under these conditions, HT-29 cells do not express any characteristics of enterocytic differentiation, even when grown in differentiation permissive conditions. We show here that the conversion of high mannose to complex glycoproteins is, however, severely reduced in HT-29 cells grown in differentiation non-permissive conditions (HT-29 Glc+) whatever the phase of growth studied. In contrast, HT-29 cells grown in differentiation permissive conditions (HT-29 Glc-) display a normal pattern of N-glycan processing in both the exponential and the stationary phase of growth. We also show that both growing and confluent HT-29 Glc+ cells accumulate Man GlcNAc2 species, thus suggesting that there is an important regulatory point at this level. We therefore conclude that the N-glycan processing may be used as an early biochemical probe for the enterocytic differentiation of HT-29 cells. Whether these early changes result from an early metabolic regulation or are the consequence of a genetic control remains to be studied. PMID- 2592436 TI - Cytovillin and other microvillar proteins of human choriocarcinoma cells. AB - Microvilli were isolated from cultured human JEG-3 choriocarcinoma cells using a gentle shearing method. The protein components of the isolated microvilli were examined by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. The major Mr 42,000 and Mr 100,000 polypeptide bands reacted with anti-actin and anti-alpha-actinin antisera, respectively. Extraction of the isolated JEG-3 microvilli with Triton X-100 left an insoluble cytoskeletal residue containing mainly actin, alpha-actin, and polypeptides of Mr 200,000, 55,000 and 35,000. The Mr 35,000 polypeptide remained insoluble only at high concentrations of free Ca2+. Immunoblotting analysis of the JEG-3 microvilli indicated that they were devoid of tropomyosin, although the total JEG-3 protein lysates gave a strong positive reaction with anti-tropomyosin antiserum. The different subcellular localization of cytovillin and tropomyosin was also shown by indirect immunofluorescence microscopy. Cytovillin, an Mr 75,000 microvillus specific membrane protein of JEG-3 cells, existed in an oligomeric form (dimer or trimer) as shown by gel filtration of Triton X-100 solubilized microvillar proteins and by native polyacrylamide gel electrophoresis of purified cytovillin. Disulfide bridges were not involved in the aggregation, because the mobility of cytovillin was similar under reducing and nonreducing conditions in SDS-PAGE. Cytovillin was shown to be closely related to ezrin, a minor component of chicken intestinal brush border microvilli. PMID- 2592438 TI - Thermal properties of young red blood cells are indicative of an age-dependent regulation of membrane-skeleton interaction. AB - The effects of red blood cell (RBC) age on membrane thermal properties have been investigated by using a 16-nitroxide stearic acid spin probe. We detected in unfractionated and most dense cells (2% fraction of circulating cells) a thermal transition at 40 degrees C that in young cells (1% fraction) was lowered at 33-35 degrees C. Spectrin seems to be directly involved in the transition detected in both young and unfractionated cells, as showed by the disappearance of the breaks after low salt extraction of spectrin. A further indication for a role of spectrin in this transition comes from its characteristic thermal unfolding above 40 degrees C. However, young cells did not show changes either in the thermal unfolding of spectrin or in the distribution of spectrin dimer, tetramer, and high oligomeric forms. These data rule out that spectrin of young RBC is modified in its thermal properties and indicate that young cells may have a different spectrin-membrane interaction. Treatment of unfractionated ghosts with an antibody specific for a fragment of the 10K domain of protein 4.1, which is fully competent for the spectrin-actin binding, produced an evident lowering of the transition temperature. The same antibody did not affect the thermal transition of young ghosts. Our results suggest that spectrin-membrane interactions may be regulated during RBC lifespan. PMID- 2592439 TI - Three-dimensional chromosome arrangement of Crepis capillaris in mitotic prophase and anaphase as studied by confocal scanning laser microscopy. AB - To estimate the extent of ordering of chromosomes, confocal scanning laser microscopy was used to make three-dimensional images from optical sections. For Crepis capillaris, which has 2n = 6 easily recognizable chromosomes, a statistically significant sample of 75 Feulgen-stained root tip anaphases was analysed. A comparison of the observed chromosome ordering and the expected random distribution showed a significant surplus of one of the arrangements with a juxtaposition of the two chromosomes with a nucleolus organizer region. Two of the arrangements with these chromosomes in opposite positions were never observed in our material. Another analysis of 30 mithramycin A-stained prophases and 30 meta- and anaphases showed partly different patterns of non-random chromosome distribution in the two stages of mitosis. A preference for an association of the homologues was observed for all pairs of chromosomes in prophase cells, whereas in meta- and anaphase the association only persisted for the nucleolus organizer chromosomes. This indicates that there may be some relocation of the chromosome positions during the transition from prophase to metaphase. In meta- and anaphase one of the arrangements with juxtaposed NOR chromosomes was preferred, i.e. the ordering in which chromosomes 1 and 3 occupied alternate positions. Probably, the nucleolus is an important factor in producing a non-random distribution, but there could be other factors that influence chromosome ordering as well. A comparison of the anaphase chromosome ordering in C. capillaris plants from very different localities, indicated that the observed non-random distribution was independent of the origin of the material. Existing models of chromosome disposition are not sufficient to explain the observed non-random chromosome ordering in C. capillaris. PMID- 2592440 TI - The effects of tunicamycin, mevinolin and mevalonic acid on HMG-CoA reductase activity and nuclear division in the myxomycete Physarum polycephalum. AB - The effects of two inhibitors of 3-hydroxy 3-methyl glutaryl-coenzyme A reductase (tunicamycin and mevinolin) on nuclear division in the myxomycete Physarum polycephalum were examined. Tunicamycin exerted a minor effect on division in synchronized cultures, whereas mevinolin delayed the second, third and fourth nuclear divisions with increasing efficiency. Mevinolin also appeared to be the more potent inhibitor of HMG-CoA reductase, which catalyses the rate-limiting step in the biosynthesis of cholesterol and other isoprene derivatives. These effects of mevinolin could be partially reversed by the addition of mevalonate, suggesting that mevinolin exerts its inhibitory effects on Physarum nuclear division by decreasing the activity of HMG-CoA reductase. PMID- 2592441 TI - Observations on ultracentrifuging wild-type and mutant (cdc2.33) cells of Schizosaccharomyces pombe. AB - Ultracentrifuging (400,000 g for 4-6 h at 4 degrees C) living wild-type cells of the fission yeast Schizosaccharomyces pombe moves the nucleus towards the ends of the cells but scarcely affects their viability. However, in the long cells produced by growing the mutant cdc2.33 for 4-6 h at the restrictive temperature (36.5 degrees C), ultracentrifuging (as above) gives an intense fluorescence with DAPI in about half of the cytoplasm in about 80% of the cells. This is probably nuclear DNA that has moved into the cytoplasm, both because of the DAPI stain and because it is removed by DNase treatment. These cells ultimately divide and are viable, and we suggest that the extended cytoplasmic DNA returns to the nucleus. PMID- 2592442 TI - The transient division block in the D9ts mutant of Tetrahymena is inducible at every cell cycle stage. AB - The temperature-sensitive mutant D9 of Tetrahymena thermophila doubles its size at restrictive temperature. It does so by complete cessation of cell division for a limited time. After resumption of proliferation, division rate and specific growth rate are the same as at the permissive temperature, thereby maintaining the new cell size. In this study a detailed analysis of the process of controlling the new cell size is presented, by probing the temperature sensitivity of cell cycle phases. It will be shown that high temperature affects the size-controlling system immediately upon shift in temperature. Temperature pulses are effective at every stage in the cycle and are executed at the time of expected division. After return to the permissive temperature, cells gradually recover from the temperature pulse as seen by a decrease in division delay. Preparation for the next division is unaffected by the temperature pulse. It occurs at the same time as in untreated controls. The results allow us to describe some features of the division initiating system. PMID- 2592443 TI - Characterization of a heat-resistant strain of Tilapia ovary cells. AB - Tilapia ovary cells (TO-2) cease to proliferate when moved from normal growth temperature of 31 degrees C to 37 degrees C, and arrest in G1 and G2 phases of the cell cycle. The ability of the arrested cells to re-enter the cell cycle when restored to 31 degrees C decreases inversely with time spent at 37 degrees C. A heat-resistant strain, TO-37c, cloned from the surviving fraction of TO-2 after heat treatment, has been found to re-enter the cell cycle with greater facility and to have a higher rate of survival. TO-37c cells have a smaller cell volume than TO-2 and show a distinct morphology at 37 degrees C. Most of the heat-shock proteins (hsps) induced on temperature change were similar, but in TO-37c the decline in the synthesis of a 27 X 10(3) Mr hsp was faster and a 37 degrees C specific 60 X 10(3) Mr hsp was missing. Ultraviolet (u.v.) sensitivity was slightly affected if heat treatment was given after irradiation. However, when cells were preheated and then u.v. irradiated, the u.v. sensitivity increased sharply for TO-2 cells but not for TO-37c. PMID- 2592444 TI - Microinterferometry of the movement of dry matter in fibroblasts. AB - We describe the use of interferometric microscopy coupled with a novel application of Senarmont compensation for detecting and quantifying the distribution of dry matter in cultured cells. In conjunction with video techniques and digital image processing, a two-dimensional, calibrated map of the dry mass distribution in an isolated cell can be obtained and digitally recorded. We have called the technique Digitally Recorded Interferometric Microscopy with Analyser Shift (DRIMAS). The method greatly facilitates the automatic recognition of cells by computer. Recorded time-lapse sequences can be used to establish a database of the growth and motility of specific cells in given experimental conditions. Databases of this type can be analysed to reveal the patterns of growth and locomotory behaviour of individual cells. We describe a systematic method of obtaining parameters of cell size, shape, spreading, intracellular motility and translocation. Auto-correlations and cross-correlations between these parameters can be detected and quantified using time series analysis, revealing potential cause/effect relationships in the mechanisms of growth and motility. Besides characterizing the overall pattern of cell behaviour, these data can also yield information about the instantaneous pattern of intracellular motility. We describe the use of finite element analysis to reveal the dynamics of the intracellular transport of dry matter. This yields the pattern of the minimum flow of dry matter required to account for the changes in its distribution. Most of this flux is not associated with the movement of visible structures and possibly represents the transport of dissociated components of the cytoskeleton. In chick heart fibroblasts, surprisingly high velocities of nearly 2.0 microns s-1 were detected during the period of increased motility following tail detachment. The total kinetic energy associated with the dry mass flux is a single parameter, which characterizes the instantaneous motility of the cell. We found that the kinetic energy of intracellular motility can be several hundred times greater than the kinetic energy of translocation. Kinetic energy may prove to be a very informative single measure of intracellular motility for assessing the effects of malignant transformation, genetic manipulations, and other experimental treatments on the locomotory machinery of the cell. PMID- 2592445 TI - Retention of ciliary ninefold structure after removal of microtubules. AB - When axonemes of isolated gill cilia from the bay scallop Aequipecten irradians are heated at 45 degrees C for a minimum of 8 min in a 10 mM-Tris-HCl (pH 8), 1 mM-EDTA solution, nearly 80% of the tubulin is solubilized but most minor structural proteins are retained in a ninefold symmetrical configuration. This remnant consists of the junctional protofilaments, derived from outer doublet tubules, interconnected by nexin linkages, with radial spoke components still directed inwards. The remnant is of the same length as the original cilium, with the junctional protofilaments attached at the distal end to the ciliary tip and at the proximal end to the basal plate. Virtually identical fractionations can be achieved with blastula cilia isolated from both arctic and tropical sea-urchin embryos. The remnant is resistant to salt up to at least 1 M concentration, judged by the constancy of protein composition. Immunoblotting with antibodies against sea-urchin sperm flagellar tektins indicates that the tektins remain within the ciliary remnant, supporting their location within the junctional protofilament domain. The fractionation is inhibited by low pH, by magnesium or calcium ions in the millimolar range, and by monovalent ions at 10-fold higher concentrations. About a quarter of the total ciliary calmodulin is bound to the axoneme at micromolar calcium levels but most is released upon thermal fractionation. Polymerization of tubulin in the presence of the remnant results in singlet microtubules, separate from the remnant proper, suggesting that doublet formation may require coordinate co-assembly of tubulin with skeletal proteins. These observations demonstrate the existence of a fibrous skeleton in the axoneme, composed largely of ciliary tektins, nexin linkages, and other structural proteins. PMID- 2592446 TI - Quantal tektin synthesis and ciliary length in sea-urchin embryos. AB - Previous work using pulse-chase labelling of embryos from the sea-urchin Strongylocentrotus droebachiensis during ciliogenesis, regeneration or steady state maintenance and elongation showed that a ciliary outer doublet microtubule associated protein, originally termed component-20, was synthesized in a fixed or quantal amount. This suggested that the limited synthesis of component-20 might limit ciliary length, since the embryo has a large pool of most other ciliary components. Labelling experiments with S. purpuratus embryos now confirm quantal synthesis of component-20, while antibodies to S. purpuratus sperm flagellar tektins identify component-20 as the ciliary equivalent of the flagellar 55 x 10(3) Mr tektin, tektin A. Sequential pulse-chase labelling at various times prior to isolation of cilia proves that the high specific activity of this protein truly reflects de novo synthesis of a structurally stable protein and not rapid protein turnover. Embryos may be animalized by growth in the presence of zinc ions, resulting in cilia averaging nearly twice the normal 20 microns length. When these embryos are pulse-chase labelled during ciliary growth and elongation, labelling of tektin A is proportional to the greater ciliary length, as is the pool of labelled but unincorporated tektins and other minor proteins. Deciliated animalized and control embryos, pulse-chase labelled during their identical phases of ciliary regeneration, incorporate labelled tektin A to the same extent and have similar pools of unincorporated proteins. The correlation of enhanced tektin A synthesis with increased ciliary length and the coincidence of tektin A synthesis with ciliary elongation are observations consistent with the hypothesis that tektin A is a ciliary length-limiting structural element. PMID- 2592447 TI - Surface views of spermatozoa as revealed by fracture-flip. AB - We have used fracture-flip to produce new, macromolecular-resolution images of the surface of boar spermatozoa. Over the head, acrosomal and postacrosomal regions display sharply demarcated, subtly different surface textures. The rim is particle-poor, as well as a region above the oblique cords over the posterior ring. The tail shows two morphologically distinct domains: (1) the principal piece is covered by a high density of parallel-helical strands and a high density of large globular particles; (2) the midpiece and the neck are covered by smaller particles with apparent random distribution. Rectangular surface specializations frequently seen near the annulus display a waffle-like texture. With the notable exception of the parallel-helical strands of the principal piece the fracture flip images of the boar spermatozoon can be directly related to the freeze fracture morphology of its plasma membrane. PMID- 2592448 TI - Properties of microtubule-free cortical residues isolated from Paramecium tetraurelia. AB - We have found that shape-preserving residues devoid of microtubules can be prepared from Paramecium using Triton X-100 at high ionic strength. These residues contain many proteins, including one showing antigenic relationship to chicken alpha-spectrin, and three showing antigenic relationship to Tetrahymena cortical proteins. These antigens have been localized by immunofluorescence microscopy, and the isolated cortical residues have been characterized ultrastructurally. These preparations should be useful in detailed studies of the structure, development and evolutionary relationships of cortical architecture in ciliated protozoa. PMID- 2592449 TI - Biochemical characterization of the proteins of Paramecium secretory granules. AB - The proteins of trichocysts (secretory granules) from Paramecium tetraurelia have been biochemically characterized. Two-dimensional electrophoresis revealed 34 major components and at least 120 minor components, most with molecular weights ranging from 14,000 to 21,000 and isoelectric points ranging from 4.8 to 5.2. Comparison of two-dimensional electrophoretic patterns of trichocysts before and after exocytosis revealed only minor changes in these patterns, although the protein matrix undergoes a striking change in morphology. To clarify the interrelationships among trichocyst proteins, two proteins from extruded trichocyst matrix were purified to homogeneity and sequenced at their N termini. Their sequences are distinct, but they share limited homology. PMID- 2592450 TI - Quantitative analysis of membrane and secretory protein processing and intracellular transport. AB - Quantitative experimental data from studies of intracellular processing and transport of secretory and membrane proteins are only rarely evaluated using kinetic modelling. Instead, the analysis of such data is usually limited to calculating either the apparent half-life or the transit time. Neither of these parameters accurately measures rates of cellular processing or transport. This paper describes a formal approach for the calculation of rate constants, half lives and lag times for single and sequential processing and transport steps. Generalized kinetic models are presented that can be used to analyse data from both pulse-chase and continuous incubation experiments with labelled amino acids or sugars. The results from a number of published studies are reanalysed using the models to demonstrate the usefulness of kinetic modelling in the routine analysis of experimental data. PMID- 2592451 TI - Invasion of a basement membrane matrix by chick embryo primitive streak cells in vitro. AB - At the time of gastrulation in the chick embryo the upper epiblast layer penetrates its own basement membrane at the primitive streak so that its cells may invade the underlying tissue space. In so forming the primary mesoderm, the cells undergo a concomitant epithelial-to-mesenchymal transformation. In this study, epiblast tissue has been explanted onto a basement membrane gel in order to examine its invasive potential. Fully ingressed primary mesoderm cells were able to penetrate the gel as individual cells, during the course of which the texture of the gel was disrupted. By contrast, epiblast tissue taken from the immediate vicinity of the primitive streak penetrated the gel, but only as a coherent tongue of cells and without gel disruption. These tongues of cells did not undergo the epithelial-to-mesenchymal transformation, and consequently spread as a epithelial sheet when replated on glass. Thus, the absence of gel disruption correlated with the failure of transformation, suggesting that these two events may be linked and that they may require in situ cell interactions for their manifestation. Tissue from the lateral epiblast failed to penetrate the gel. Instead, this tissue either spread on the gel surface or rounded up into a hollow sphere with the basal surface of the cells innermost. In the former case, despite the cell spreading, no lamina densa was organized beneath the sheet, but in the latter case polarity reversal occurred with the formation of a new lamina densa at the cell-gel interface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592452 TI - Effect of hypoxia upon the growth and sprouting activity of cultured aortic endothelium from the rat. AB - Endothelial cells were obtained from the aortas of Wistar rats by collagenase digestion. Cells were grown to confluence in medium 199 enriched with L-glutamine but without specific growth factors. Cells were subcultured into 35 mm dishes or 25 cm2 flasks coated with fibronectin. For cell growth studies, cells were seeded onto multiwell plates or 35 mm dishes. In two experiments the cells were grown in an hypoxic atmosphere of 5.3% O2 and in a third the level of oxygen was 2.5%. Control cultures for each experiment were grown in 5% CO2 and air. Cell populations were counted at 2-day intervals and at the termination of each experiment the cells were fixed and the area of each plate or flask occupied by sprouting cells was assessed by point counting. Endothelial cells grown in 5.3% O2 grew more rapidly and attained confluence earlier than in the controls. An atmosphere of 2.5% O2 did not accelerate growth but neither did it inhibit it, so after 9 days there were as many hypoxic cells as there were controls. Hypoxia also stimulated sprouting activity to occur earlier and to become much more extensive than in control cultures. Under the influence of hypoxia, sprouting consisted of complex anastomotic or arborizing patterns forming syncytium-like masses beneath the monolayer of oval cells. This process appeared to originate from foci of altered endothelial cells that had become retracted, smaller, elongated and migratory, and which displayed increased immunoreactivity for factor VIII antigen. It was concluded that a level of hypoxia, similar to that in systemic veins, stimulates growth of arterial endothelium and provokes enhanced sprouting activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592453 TI - A rapid and convenient assay for counting cells cultured in microwell plates: application for assessment of growth factors. AB - There is currently much interest in the role of mediators that regulate cell proliferation. Methods to assay proliferative effects of such mediators usually involve cell counting techniques, which are tedious to perform, or methods based on uptake of radiolabelled thymidine, which may be prone to errors caused by precursor pool artefacts. We describe here an assay for estimating the number of adherent cells present in a microculture and its application to the study of growth factors. The assay depends on the binding of Methylene Blue to the fixed monolayer at pH 8.5 and, after washing the monolayer, release of dye by lowering pH. The use of an elution solvent containing acidified ethanol ensures a linear correlation between absorbance of the dye and cell number, and enables the assay to be carried out in 96-well plates measuring absorbance with an automated vertical light-path microplate photometer. The assay is rapid, highly reproducible and easy to perform, making it ideal for screening large numbers of samples. It was shown to be applicable to a number of foetal and adult cell lines derived from man and experimental animals. It was also demonstrated to be useful for assaying purified growth factors and detecting growth promoting activity in cell and tissue extracts. PMID- 2592454 TI - Resolving multiple overlapping calorimetric transitions by use of a microcomputer: studies on erythrocyte membranes. AB - Buffer changes and certain drugs cause temperature shifts, amplitude changes, and transition broadening in the differential scanning calorimetric (DSC) analysis of erythrocyte membranes. However, it has been difficult to interpret and quantitate these shifts and changes because the scans are composed of multiple overlapping transitions and because more than one transition may be simultaneously affected. An empirical approach has been developed by using Gaussian modeling to resolve these calorimetric transitions. Data analysis was carried out on a microcomputer using a nonlinear regression program (PCNONLIN) to fit the data scans. These results show that changes in the calorimetric scans of erythrocyte membranes due to alterations in the buffer environment, such as pH and osmolarity, can be resolved by fitting the data scans with the proposed mathematical model and optimizing the resolution parameters with PCNONLIN. In addition, resolution uncovered hidden characteristics that may not have been readily evident. Under certain conditions, for example, apparent transition shifts were shown to actually be amplitude changes and transition broadening. Determination of the limitations and validity of this method was accomplished with simulation studies. This technique offers a simple means for fitting overlapping DSC transitions by use of a commercially available nonlinear regression program that can be run on a microcomputer. PMID- 2592455 TI - Host-enhanced chemical indexing in technical databases. AB - Many files that index engineering, physics, or other technical literature contain references to chemical compounds. Complex chemical formulas in the title or abstract often contain special characters, for example, (,), [,], +, -, degrees, and %. Upper and lower case letters often are also included. A search of these formulas and symbols in the basic index is next to impossible because the terms in this field are usually parsed to all alphanumeric characters without sensitivity to case. It is possible for an online host to use a character recognition algorithm to scan the title and abstract data for special characters or character strings and place them in a separate index field when such files are loaded. Such an algorithm has been designed by Fachinformationszentrun Energie, Physik, Mathematik GmbH in Karlsruhe, West Germany (FIZ Karlsruhe), the European service center of STN International, the scientific and technical information network. This algorithm recognizes and analyzes chemical formulas, material descriptions, alloys, and eutectic systems as well as nuclear reactions and dopings that appear in the title, abstract, or other fields. These character strings are converted into a standardized form and placed in a new field (the element terms field) which is supplied by the online host during the loading process. A checklist of allowed terms (symbols and chemical formulas) is used to prevent irrelevant terms from being mistaken for legitimate chemical symbols. For instance, the algorithm can recognize that CPU (central processing unit) is not a legitimate chemical formula. It is easy to demonstrate the utility this additional index supplies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592456 TI - [Perforations of the colon. Apropos of 74 cases]. AB - 74 colic perforations were surgically handled between 1975 and 1988. Among the non-traumatic perforations, which represent 74% of this series, 39 cases (71%) complicated the course of acute diverticulitis, 9 cases (15%) were due to cancers and 7 cases (13%) were of miscellaneous origin. Traumatic perforations (26%) were iatrogenically induced in 84% (16 cases). In 78% the perforation was located in the sigmoid or recto-sigmoid. The treatment consisted in performing either a diverting colostomy (30 cases--40%) or a colic resection (44 cases--60%) with or without immediate anastomosis (respectively 10 cases--13.5% and 34 cases--46%). The overall mortality was 10.8%, which referred to etiology, turns to be 15% (3/19 cases) in traumatic perforations, 13% (5/39 cases) in diverticulitis and 0% in cancer. Related to treatment, mortality reached 23% for derivation and drainage procedure and 2% for resection. Post-operative complications were respectively 10% and 47%. Among post operative complications (22 cases--29%) 11 patients were reoperated on with an additional mortality of 18%. These results give strong evidence to the reliability and value of urgent colic resection in perforated colon and enhance the necessity of undelayed operation. PMID- 2592457 TI - [Vascular complications of fractures of the pelvis]. AB - Fifteen cases of severe fractures of the pelvis associated with vascular complications are reviewed. The operational strategy remains controversial when faced with these life threatening traumatic lesions. The chief cause of mortality of these fractures is subperitoneal or retroperitoneal expanding hematoma, the natural course and evolution of which are presently well known and better explored thanks to modern imaging technology. Early-phase intensive care and intervention radiology are partly responsible for a change in the immediate therapeutic attitude. Nonetheless, in hemorrhagic poly-traumatic patients, surgical treatment is still required and remains a method non devoid of pitfalls. PMID- 2592458 TI - [Facial injuries caused by firearms. Practical approach in emergencies]. AB - Firearm injuries to the face are often a disconcerting clinical problem for the non specialized surgeon. The aim of this article is to de-mystify this emergency situation, which is common in Maxillo-facial units, and requires rigorous management and respect of well established general surgical principles. The authors subsequently review the need for secondary repair by a maxillo-facial and plastic surgeon. PMID- 2592459 TI - [Long-term results of surgery of primary hyperparathyroidism]. AB - The late results of operation for primary hyperparathyroidism were analysed in 52 patients operated between 1971 and 1987. All patients have a minimal 5 years follow-up, and answered a mailed questionnaire concerning their present state of health and recent serum calcium level. Recurrent hypercalcemia occurred in 5.7%. Hypocalcemia occurred in 30% immediately after operation; in 11.5% at six months, and in 7.7% at the final follow-up. The pathogenesis of such hypocalcemia is discussed. 66% of patients with urinary calculi are cured after neck exploration and urologic procedure. Finally 86.6% of the patients are normocalcemic at the final follow up, acting for the efficient and lasting character of the surgical treatment in primary hyperparathyroidism. PMID- 2592460 TI - [Compressive goiters. Apropos of 80 cases]. AB - Our retrospective study is based on 80 compressive goitres collected over a period of 7 years in the general surgical department of the Ibnou Rochd University Teaching Hospital, Casablanca. Dyspnea was the predominant clinical manifestation and was encountered in 82.5% of cases, followed by dysphonia (65%), dysphagia (46%) and finally venous compression (8.7%). Hyperthyroidism was encountered in 26.25% of cases, 57% of these being due to Grave's disease. The goitre extended mediastinally in 38% of cases but resection was possible on cervicotomy alone. Post-operative sequelae were minor in nature, though one death did occur. On histological examination 85% of these goitres were benign and only 15% were of a malignant nature. This is in agreement with the data in the literature which confirms that compression is not synonymous with malignancy. PMID- 2592461 TI - [Surgery of the adrenal glands in Cushing's syndrome]. AB - Our surgical experience for the Cushing syndrome, reviewed in 23 patients. The accuracy of localizing adrenal lesions increased recently. The present study shows that, adrenal surgery, after accurate diagnosis and localisation, can be performed with low morbidity and mortality. PMID- 2592462 TI - [Liver abscess caused by gallbladder perforation during pyocholecystitis: apropos of a case]. PMID- 2592463 TI - [Primary retroperitoneal leiomyosarcoma simulating a renal tumor]. PMID- 2592464 TI - [Gastric leiomyoblastoma. Apropos of a case and review of the literature]. PMID- 2592466 TI - [Reparation of sequelae of penile-scrotal and perineal gangrene. Apropos of 4 cases]. AB - The authors report different techniques for surgical reconstruction of the sequelae of penile, scrotal and perineal gangrene. The repair of skin defects and the reconstruction of the scrotum requested several interventions. Where the scrotal skin loss was limited to a 1/2 of scrotum, the testis could be covered by mobilising the surrounding rim. When the disease was confined to the penis or inguinal region, skin cover has been provided by free grafts. More elaborate techniques of skin cover were necessary when the disease was extended to the whole scrotum: a fasciocutaneous flap from the thigh was used for reconstruction of the scrotum. The scrotal myocutaneous flap was used to cover skin and anterior urethral loss of tissue. PMID- 2592465 TI - [Acute peritonitis complicating intestinal endometriosis. A case report with comments]. AB - The authors report a rare case of ileo-caecal-appendicular endometriosis which presented as an acute peritonitis. In their commentary they review the notions concerning the most frequent acute manifestations in the intestinal localization and discuss the therapeutic management and prognosis of the condition. PMID- 2592467 TI - Mothers' speech to autistic children: a preliminary causal analysis. AB - Changes over time in the language patterns of autistic children and their parents were examined during the course of a home-based intervention programme. Although the language used by parents to their autistic children was not deficient, language modification procedures were found to lead to rapid changes in the verbal interaction between parents and children. Parents in the non-intervention, control group showed little change in their communication style. In the experimental group, but not in the control group, a close relationship was found between increases in the use of language-eliciting utterances by their mothers and improvements in children's socialized language. The pattern of association between parent and child language suggested that the main effect was of the parent on the child but that the extent of the child's language handicap constrained what could be achieved by treatment. PMID- 2592468 TI - Parent-child dyadic gaze patterns in fragile X males and in non-fragile X males with autistic disorder. AB - Parent-child dyadic gaze patterns were examined in fragile X [fra(X)] males and in non-fra(X) autistic males across three age groups--early childhood, middle childhood and adolescence. Absolute probabilities of social gaze did not significantly differ across diagnostic groups. Event lag sequential analyses indicated that fra(X) males were sensitive to social gaze initiation by their parents but found eye contact aversive. Non-fra(X) autistic males, by contrast, were insensitive to parent-initiated social gaze, and did not find eye contact aversive. Implications for research on the social characteristics of fra(X) and autistic children are discussed. PMID- 2592469 TI - Do autistic children differ from retarded and normal children in Piagetian sensorimotor functioning? AB - Piagetian sensorimotor functioning of 10 autistic, 10 retarded, and 10 normal children, closely matched on mental age, was assessed with the Dunst revision of the Uzgiris and Hunt scales of infant psychological development. The three groups showed no significant differences in overall performance or specific subtest performance as revealed by estimated developmental ages, number of failed items, and Piagetian stage levels. These findings, which are contrary to previous reports of early sensorimotor deficits specific to autism, suggest that the long term cognitive deficits in autism are more in symbolic thinking, which does not emerge until the end of the sensorimotor period. PMID- 2592470 TI - Recognition and expression of emotional cues by autistic and normal adults. AB - High-functioning autistic adults were compared with normal adults using a battery of tests devised to assess the recognition and expression of emotional cues in both facial and vocal modalities. The autistic subjects were relatively impaired in both the appreciation and production of emotional expressions. Although no one test provided a clear-cut separation of the groups at the individual level, composite scores did separate the groups quite well. It is suggested that this battery of tasks may have some value in family genetic studies of autism that need to identify subclinical deficits that might be aetiologically linked with autism. PMID- 2592471 TI - Reliability of psychiatric diagnosis in referred adolescents. AB - The authors report a reliability study of the DSM-III diagnostic system in a series of 393 adolescent referrals diagnosed by two clinicians over a period of 3 years. Overall reliability (kappa) was 0.59. However, most of the frequently used diagnoses had reliabilities of 0.7 or higher. Dysthymic, Adjustment, Overanxious and Avoidant Disorders showed poor diagnostic agreement (kappa below 0.4). The patterns of agreement across this and other studies suggest that diagnostic criteria for Affective, Anxiety and Adjustment Disorders are in need of further improvement. PMID- 2592472 TI - Subgrouping conduct disorder by psychiatric family history. AB - The family history of psychiatric disorders, and clinical and demographic characteristics of boys with pervasive aggressive conduct disorder (PACD) were compared to those of boys with situational aggressive conduct disorder and controls. Boys with PACD came from lower socioeconomic backgrounds, had an earlier age of onset, and higher rates of hyperactivity and inattention than boys in the other two groups. Their mothers abused drugs more often than those of boys in the other two groups, while their fathers had more frequent antisocial behavior. Alcohol abuse was more prevalent among fathers of both conduct disorder groups, compared to the fathers of controls. PMID- 2592473 TI - Differentiation of motor activity of normally active and hyperactive boys in schools: some preliminary results. AB - All non-task-related body movements during school hours were listed in 11 normally active and 12 hyperactive boys. The mean number of movements was 48 +/- 7 per 45 minutes in the normal actives and 79 +/- 16 per 45 minutes in the hyperactives. The rather monotonous increment and decrement of motor activity during the 4-hr registration period was noticed only in hyperactive boys. These results could be a consequence of a circadian rhythm, as there was independence of type of school hours and of teacher personality. The cyclical level of activity in hyperactive boys was sometimes in the range of the normal actives. PMID- 2592475 TI - Methodologic note for child epidemiological surveys: the effects of instructions on estimates of behavior prevalence. AB - This paper examines the effects of a change in the wording of the Child Behavior Checklist (CBCL) instructions for the 0 category on the reported prevalence of behaviors among normal children by their parents. Convenience samples of parents were randomly allocated to complete CBCL items using either the standard instructions "not true" or "never or not true" to describe the 0 category. Adding the word "never" to describe the 0 category decreased parents' use of that category and increased their use of the adjacent, 1, category. Implications of these findings are discussed. PMID- 2592474 TI - An epidemiological study of behaviour problems in school children in urban areas of Beijing. AB - A total of 2432 primary school children, aged 7-14 yrs. in urban areas of Beijing, were evaluated with the Children's Behaviour Questionnaire developed by Rutter. The frequency of behaviour problems in primary school was 8.3%-7.4% antisocial behaviour and 0.62% neurotic behaviour. Behaviour problems were higher in boys than girls: antisocial behaviour was dominant in boys, while neurotic behaviour was common in girls. The frequency of behaviour problems varied significantly with the different social environments in which the children were brought up, but were not different between one-child families and those with more children. PMID- 2592476 TI - Maternal psychological state and infant development with mothers under twenty: a research note. AB - Data were used from a longitudinal study of mothers under 20 and their firstborn children to investigate some factors possibly associated with the developmental progress of the children at 21 mths of age. Developmental progress was considered as a function of whether other adults lived with the mother and child, whether it was a dual parent household, maternal age, aspects of maternal psychological state, child gender and cooperation. Child gender and cooperation and the woman's satisfaction with motherhood were related to children's developmental progress. Possible reasons for the observed interrelationships are discussed. PMID- 2592477 TI - First International Symposium on High-Performance Capillary Electrophoresis. Boston, MA, April 10-12, 1989. PMID- 2592478 TI - Characterization of a post-column reaction-laser-induced fluorescence detector for capillary zone electrophoresis. AB - Several modifications have been made to a post-column labeling system for use with capillary zone electrophoresis. Fluorescence excitation is now performed with a helium-cadmium laser rather than an arc lamp. The focusability of the laser beam allows the use of larger diameter capillaries in the post-column reactor without the excessive band broadening observed previously. These larger capillaries can be assembled in the reactor much more easily. Another improvement is that the flow-rate of the labeling reagent can now be accurately controlled and determined. Incorporating these changes, the performances of two reactors with capillaries of the same dimensions are compared. PMID- 2592479 TI - Coupling of capillary zone electrophoresis and capillary liquid chromatography with coaxial continuous-flow fast atom bombardment tandem sector mass spectrometry. AB - The coaxial continuous-flow fast atom bombardment (FAB) system has proven to be very useful for interfacing capillary liquid chromatography and capillary zone electrophoresis (CZE) with sector mass spectrometry (MS). The interface can be used for the acquisition of both MS and MS-MS spectra from femtomole levels of non-volatile and/or thermally labile analytes while maintaining separation efficiencies of hundreds of thousands of plates. The use of coaxial fused-silica capillary columns to independently deliver the microcolumn effluent and the FAB matrix to the tip of the FAB probe offers the following advantages: the composition and flow-rates of the two liquid streams can be independently optimized; the FAB matrix does not effect the microcolumn separation process; peak broadening is minimized since the two liquid streams do not mix until they reach the tip of the FAB probe where ion desorption occurs; and, with CZE, active electrophoretic transport delivers the analytes directly to the FAB probe tip. These features combine to make this coaxial continuous flow fast atom bombardment interface particularly well suited for use with microcolumn separation methods. PMID- 2592480 TI - Harnessing electrical forces for separation. Capillary zone electrophoresis, isoelectric focusing, field-flow fractionation, split-flow thin-cell continuous separation and other techniques. AB - A simple analysis, first presented twenty years ago, showed that the effectiveness of a field-driven separation like electrophoresis, as expressed by the maximum number of theoretical plates (N), is given by the dimensionless ratio of two energies N = -delta mu ext/2RT in which -delta mu ext is the electrical potential energy drop of a charged species and RT is the thermal energy (R is the gas constant and T is the absolute temperature). Quantity -delta mu ext is the product of the force F acting on the species and the path length X of separation. The exceptional power of electrophoresis, for which often N approximately 10(6), can be traced directly to the enormous magnitude of the electrical force F. This paper explores the fundamentals underlying several different means for utilizing these powerful electrical forces for separation, including capillary zone electrophoresis, gel electrophoresis, isoelectric focusing, electrical field-flow fractionation and split-flow thin continuous separation cells. Remarkably, the above equation and its relatives are found to describe the approximate performance of all these diverse electrically driven systems. Factors affecting both the resolving power and separation speed of the systems are addressed; from these considerations some broad optimization criteria emerge. The capabilities of the different methods are compared using numerical examples. PMID- 2592481 TI - Capillary zone electrophoresis and isotachophoresis-mass spectrometry of polypeptides and proteins based upon an electrospray ionization interface. AB - The special capabilities of the capillary electrophoresis electrospray ionization mass spectrometer interface for the analysis of peptides and proteins with molecular weights extending to in excess of 100,000 are reviewed. The dynamic combinations of both capillary zone electrophoresis and capillary isotachophoresis with electrospray ionization are illustrated for mixtures of peptides and proteins. Myoglobin and cytochrome c detection limits were ca. 100 fmol. The potential extension of these methods for determination of the primary structure (sequence) of polypeptides using tandem mass spectrometry is shown to be facilitated by the high charge state of ions produced by the electrospray interface. The relevance of these results for advances in analytical biochemistry are discussed. PMID- 2592482 TI - Preliminary investigation of ion mobility spectrometry after capillary electrophoretic introduction. AB - Using standard capillary electrophoretic and ion mobility methods, several electrospray interface designs were investigated for the capillary electrophoretic introduction of samples into the ion mobility spectrometer. Of the interfaces investigated, the flow assisted interface and the direct coupled interface showed the most promise. These preliminary experiments were encouraging. The ion mobility spectrometer coupled with a capillary electrophoretic introduction system operated with excellent separation efficiency and ion mobility reproducibility. Using tetrabutylammonium iodide, the number of theoretical plates for the spectrometer was calculated to be 3.10(3) and reduced mobilities were found to be reproducible with a relative standard deviation of 1.43%. Because of the desire to hold the spectrometer as hot as possible, the solvent would often vaporize in the interface, creating an unstable spray and inhomogeneities in the electrophoretic field. More work is needed to improve the spray process which contributed to the overall noise of the system and to eliminate the phenomenon of solvent vaporization which limited the reproducibility of electrophoretic migration times. PMID- 2592483 TI - Coupling capillary zone electrophoresis and continuous-flow fast atom bombardment mass spectrometry for the analysis of peptide mixtures. AB - Combined capillary zone electrophoresis (CZE)-continuous-flow fast atom bombardment (CF-FAB) mass spectrometry is described for the analysis of mixtures of peptides. A 90 cm x 50 microns I.D. fused-silica capillary column was used for electrophoretic separations and was connected to the CF-FAB probe via an interface which allows a total flow into the mass spectrometer of about 5 microliters/min. Solutions of peptides were pneumatically loaded onto the CZE capillary, providing sample amounts of 0.1-20 pmol. The magnetic mass spectrometer was scanned over the desired mass range, usually between m/z 500 and 2500. Results are shown for separation and analysis of mixtures of synthetic peptides and also for protease digests of recombinant human growth hormone and horse heart cytochrome c. PMID- 2592484 TI - Gel permeation chromatography combined with capillary electrophoresis for microanalysis of proteins. AB - A new type of apparatus for the analysis of complex protein mixtures, in which gel permeation chromatography was combined with capillary electrophoresis, was constructed. Proteins were separated according to their molecular size in the first step, then separated according to their electrophoretic mobility in the second step. The outlet of a microbore column was connected with the sample injection port of a capillary electrophoresis apparatus. All the procedures of chromatography and electrophoresis were automated with the aid of a system controller. Preliminary results on the separation of proteins are presented. PMID- 2592485 TI - Capillary electrophoresis of proteins in buffers containing high concentrations of zwitterionic salts. AB - A method for improving protein separations in capillary zone electrophoresis utilizing high concentrations of zwitterionic buffer additives was examined. Lysozyme and alpha-chymotrypsinogen A were used as test proteins in untreated fused-silica capillaries in buffers of pH ca. 7.0 and 9.0 The zwitterion containing buffers were compared with buffers containing high ionic salt concentrations and a buffer containing a combination of high ionic salt and high zwitterion concentrations. Over 100,000 theoretical plates were obtained in less than 30 min. for both test proteins in a pH 7 buffer containing both trimethylglycine and potassium sulfate. The advantages and disadvantages of this technique compared with those of other methods used to prevent protein adsorption are discussed. PMID- 2592486 TI - Capillary zone electrophoresis of oligonucleotides. Factors affecting separation. AB - The influence of various parameters affecting separation of oligonucleotides by capillary zone electrophoresis has been examined. The effects of pH, ionic strength, and various additives, including highly charged cations such as spermine, were studied. Using polycytidines as model compounds, it was demonstrated that pH in the range of 5-8 and ionic strength in the range of 20 200 mmol/l do not influence the separation of oligonucleotides substantially. However, with the addition of spermine to the background electrolyte, migration order was inverted as the effective mobilities of the larger oligonucleotides were greatly decreased. With the addition of spermine and sodium dodecyl sulfate, the separation+ of these model oligonucleotides was also significantly affected. The best separation of a homologous series of polycytidines was obtained with a background electrolyte containing 60 mmol/l histidine, 30 mmol/l glutamic acid, 50 mmol/l sodium dodecyl sulfate and 3 mmol/l spermine. PMID- 2592487 TI - Separation of the human transferrin isoforms by carrier-free high-performance zone electrophoresis and isoelectric focusing. AB - Human transferrin isoforms, i.e., molecules with different carbohydrate contents which differ from each other by only one negative charge, were resolved by high performance zone electrophoresis in free solution. The di-, tri-, tetra-, penta-, hexa- and heptasialo transferrins could be assigned in the electrophoretic pattern. The pattern changed when iron-free transferrin was treated with neuraminidase, which splits off the sialic acid from the carbohydrate chains. The final digest contained transferrin molecules without sialic acids, as was confirmed by isoelectric focusing. PMID- 2592488 TI - Separation of collagens by capillary zone electrophoresis. AB - Collagen (types I, II, V, IX and XI) constituting polypeptide chains and their polymers and cyanogen bromide-cleaved peptides of collagen type I and type III were investigated by means of capillary zone electrophoresis. Separations were effected in 2.5 mM sodium tetraborate buffer in less than 15 min. A 50 cm x 0.1 mm I.D. fused-silica capillary was used. The separations were run at 18 kV per capillary. The results of the separation were monitored at 220 nm with an on-tube detection system. Using the Offord equation, relative retention times of cyanogen bromide cleavage fragments were plotted against M(2-3)/Z, where M is the molecular mass of a polypeptide and Z its valency. A linear relationship was observed. Collagen alpha-chains and their polymers were also satisfactorily resolved. PMID- 2592489 TI - Characterization of human growth hormone by capillary electrophoresis. AB - Production of proteins by recombinant DNA technology for use as pharmaceuticals requires the use of the most powerful tools of analytical protein chemistry in order to confirm purity and identity of the product and reliability of the process. Capillary electrophoresis is an emerging technology that shows high sensitivity and selectivity and may have promise in this application. The technique combines the instrumental control and quantification features of high performance liquid chromatography with the separating power of electrophoresis, and thereby has attracted broad interest. In this report, human growth hormone expressed in bacteria has been analyzed by both free zone electrophoresis and isoelectric focusing in a coated capillary to demonstrate the separation of the native molecule from its deamidated variant. A capillary zone electrophoretic tryptic map has also been developed and characterized. This map complements the widely employed reversed-phase high-performance liquid chromatography tryptic mapping systems that are important in protein characterization. Certain drawbacks to capillary zone electrophoresis compared to other analytical methods are noted, including relatively poor reproducibility and low sample tolerance. For applications as demonstrated here, however, the speed, separating power and sensitivity of the technique compensate for these shortcomings. PMID- 2592490 TI - Capillary zone electrophoresis of peptide fragments from trypsin digestion of biosynthetic human growth hormone. AB - Capillary zone electrophoresis (CZE) was applied to the separation of the 19 peptide fragments produced by enzymatic digestion of human growth hormone (hGH). The fragments of hGH produced by trypsin digestion under non-reducing conditions were identified in the electropherogram. Almost all of the fragments were resolved by CZE in less than 15 min. There is a marked difference in selectivity between reversed-phase high-performance liquid chromatography (RP-HPLC) and CZE. CZE is demonstrated to be a powerful complement to RP-HPLC for routine identification of hGH using trypsin digests. PMID- 2592491 TI - Sensitive resolution of Giardia lamblia membrane antigens. PMID- 2592492 TI - New ultraviolet labelling agents for high-performance liquid chromatographic determination of monocarboxylic acids. AB - New UV-labelling agents have been synthesized, which are designed to convert monocarboxylic acids into their highly UV-absorbing derivatives for enhancement of the sensitivities of UV detection in high-performance liquid chromatography. The reagents are p-nitrobenzyl, 3,5-dinitrobenzyl and 2-(phthalimino)ethyl p toluenesulphonates. Each has been prepared by reaction of p-toluenesulphonyl chloride with p-nitrobenzyl alcohol, 3,5-dinitrobenzyl alcohol or N (hydroxyethyl)phtalimide, respectively, in the presence of sodium hydroxide, and they are stable in the solid state for at least 6 months. Monocarboxylic acids were derivatized to their p-nitrobenzyl, 3,5-dinitrobenzyl or 2 (phthalimino)ethyl esters with each of the above reagents, respectively, then determined by high-performance liquid chromatography with UV detection. In the UV labelling with each reagent, 18-crown-6 was used as the catalyst. The effects of the reaction solvent, reaction temperature and time and the concentrations of each reagent and the catalyst were also examined. PMID- 2592493 TI - Identification of peptides, from a peptic haemoglobin hydrolysate produced at pilot-plant scale, by high-performance liquid chromatography and mass spectrometry. AB - Gel-permeation high-performance liquid chromatography (HPLC) and reversed-phase HPLC were used to separate a mixture of peptides, produced at pilot-plant scale by peptic hydrolysis of bovine haemoglobin. Volatile buffers were employed in both HPLC techniques in order to get an easy recovery of peptides for further applications. The method is more rapid than low-pressure gel filtration. Amino acid analysis and fast atom bombardment mass spectrometry confirmed the purity, and allowed accurate molecular weights to be determined, for isolated peptides. These data demonstrate that such efficient techniques, usually used to resolve hydrolysates obtained in batch with pure substrates and highly specific enzymes, can be employed to resolve complex enzymatic hydrolysates of crude protein. PMID- 2592494 TI - The separation of pancreatic procarboxypeptidases by high-performance liquid chromatography and chromatofocusing. AB - Different experimental conditions and chromatographic supports have been selected for the most efficient and rapid purification of procarboxypeptidases from porcine and human pancreas by different high-performance liquid chromatography (HPLC) variants (anion exchange, reversed phase and gel filtration). Anion exchange chromatography was found to be the most capable and permitted the isolation, in a single step, of three different porcine procarboxypeptidases (2A + 1B forms) and five different human procarboxypeptidases (2B + 3A forms) in a native and pure state from whole pancreas extracts. Other pancreatic proproteases are also cleanly isolated in the same step. Reversed-phase chromatography under mild conditions separated porcine or human procarboxypeptidases A from other pancreatic proteins in a very short time but was unable further to subfractionate the same proteins. The sequential use of gel filtration (or anion-exchange) and reversed-phase HPLC chromatography permitted, in a simple way, the isolation and dissociation of the strongly bound components of the binary complexes between procarboxypeptidases A and proproteinase E in either porcine or human pancreas extracts. Chromatofocusing on a fast protein liquid chromatographic support was also found to be a very efficient technique, showing a slightly lower capability to separate procarboxypeptidases than anion-exchange HPLC though in a much shorter time and in larger quantities. PMID- 2592495 TI - Conversion of a conventional packed-column gas chromatograph to accommodate megabore columns. I. Evaluation of the system for organophosphorus pesticides. AB - A conventional packed-column chromatograph was modified for use with a megabore column using a commercial conversion kit, with the intention of developing a multi-residue method for organophosphorus pesticides. The results indicate that the conversion does not affect the resolving power of the megabore column, since fourteen organophosphorus pesticides could be separated in a single injection. The megabore column in such a system proved to be much more efficient than a packed column in terms of resolution and qualitative reproducibility, and comparable with a similar column in a dedicated chromatograph. However, the conversion did not affect the quantitative reproducibility of the system to some degree, as indicated by coefficients of variation between 5 and 27%, although it was determined that the particular nitrogen-phosphorus detector system (filament bead) used in this study was partly responsible for the variation. Nevertheless, calibration curves were obtained down to 0.1 ng per component, and a limit of quantitation of 1.0 ng was established for each component in a sample containing fourteen organophosphorus compounds. The results indicate that the system is sufficiently reproducible to develop a multi-residue method for organophosphorus pesticides in environmental waters. PMID- 2592496 TI - Determination of phenoxyacid herbicides in water. Polymeric pre-column preconcentration and tetrabutyl-ammonium ion-pair separation on a PRP-1 column. AB - Optimum conditions for preconcentration of phenoxyacid herbicides from water on polymeric material and separation on an analytical column (PLRP-S) and PRP-1 respectively) have been achieved. The method consists of (a) an on-line preconcentration at pH 3, (b) clean-up with four (precolumn) bed volumes of acetonitrile-water (30:70) at pH 3 and (c) isocratic analytical separation at pH 11 with 0.01 mol/l tetrabutylammonium as the ion-pair reagent and acetonitrile water (30:70) as the eluent. Data on the repeatability of the method, sample flow dependence and sorption capacity are reported. For reliable integration of the chromatogram a clean-up step was introduced. This washing procedure however is more effective for tap-water than for surface water samples. The results of the method are promising and indicate that 10-50 ml of surface water can be applied to the precolumn without breakthrough. Detection limits in surface water samples are 0.1-0.5 micrograms/l whereas those in tap water are 10-50 ng/l. The applicability fo the method was tested. The results of this method were in good agreement with gas chromatographic-mass spectrometric results, and only ca. 0.1 microgram/l lower over the entire range, whereas the analysis time was much shorter. The potential of this technique for automation was demonstrated using a microprocessor-controlled column-switching unit, resulting in a reduction of the total analysis time to ca. 20 min. PMID- 2592497 TI - Determination of panaxytriol, a new type of tumour growth inhibitor from Panax ginseng, by capillary gas chromatography. PMID- 2592498 TI - Conversion of a conventional packed-column gas chromatograph to accommodate megabore columns. II. Determination of organophosphorus insecticides in environmental water. AB - Several methods involving solvent extraction or solid extraction (Amberlite XAD resins) were studied for the multi-residue recovery of fourteen organophosphorus compounds in water. It was found that extraction with ethyl acetate in a salted medium provided the most consistent data, both in terms of number of compounds recovered and percentage recovery. Amberlite XAD resins gave consistently high recoveries, and this was attributed to a matrix effect upon the particular nitrogen-phosphorus detector. The evaluation was made using a megabore column installed in a conventional packed-column chromatograph, and the results show that such a system is amenable to the multi-residue analysis of organophosphorus pesticides at very low costs. PMID- 2592499 TI - Recovery of proteins and peptides with nanogram loads on non-porous packings. PMID- 2592500 TI - Separation of rat liver HSP70 and HSP71 by high-performance liquid chromatography with a hydroxylapatite column. PMID- 2592501 TI - Separation of homologues of methyl ester and 3-O-acetyl methyl ester derivatives of the corynomycolic acid fraction from Corynebacterium pseudotuberculosis. PMID- 2592502 TI - Isolation of the aromatic heptaenic antibiotics trichomycin A-F by high performamance liquid chromatography. PMID- 2592503 TI - Rapid quantification of paraquat and diquat in serum and urine using high performance liquid chromatography with automated sample pretreatment. PMID- 2592504 TI - High-performance liquid chromatographic screening method for low levels of nicarbazin in eggs with off-line cartridge sample clean-up. PMID- 2592505 TI - Determination of 75Se-labelled selenite and metabolites in plasma and urine by high-performance liquid chromatography with on-line radioactivity detection. AB - A reversed-phase ion-pair high-performance liquid chromatographic method with on line radioactivity detection for the simultaneous determination of 75Se-labelled selenite and metabolites has been developed. With this system a good resolution of various radiolabelled selenium complexes can be achieved. The detection limit of the radioactivity detector (signal-to-noise ratio = 3) is 49 pg of selenium (specific activity of 3 GBq/mg selenium) per millilitre of urine or plasma ultrafiltrate. The detector response is independent of both the chemical structure of the selenium complexes and the matrix composition of the samples. This method may serve as a reference system for other high-performance liquid chromatographic systems with less specific and sensitive detectors. PMID- 2592506 TI - Peculiar features of application of pH gradients formed in borate buffer with a polyhydroxy compound for separation of proteins in a free-flow electrophoretic apparatus. AB - The use of pH gradients in borate buffer with a polyhydroxy compound for separation of proteins in a free-flow electrophoretic apparatus is outlined. The composition of the pH gradients, the free-flow apparatus design and its operation, and the main causes of failures in the protein separation are considered. PMID- 2592507 TI - Determination of a new angiotensin-converting enzyme inhibitor (CS-622) and its active metabolite in plasma and urine by gas chromatography-mass spectrometry using negative ion chemical ionization. AB - A sensitive and specific gas chromatographic-mass spectrometric method for the simultaneous determination of angiotensin-converting enzyme inhibitor (I, CS-622) and its active desethyl metabolite (II, RS-5139) in plasma and urine was developed. Compound D5-RS-5139 was used as an internal standard and measurements were made by electron-capture negative ion chemical ionization. Extraction from plasma and urine was carried out using Sep-Pak C18 and silica cartridges. The extract of plasma or urine was treated with diazomethane followed by trifluoroacetic anhydride to convert I and II into their methyl ester trifluoroacetyl derivatives. The detection limit of I and II was 0.5 ng/ml in plasma and 5 ng/ml in urine. The proposed method was satisfactory for the determination of I and II in plasma and urine with respect to accuracy and precision. Thus it is suitable for measurement of bioavailability and pharmacokinetics of I and II in body fluids. PMID- 2592508 TI - Simultaneous quantitation of salivary carbamazepine, carbamazepine-10,11-epoxide, phenytoin and phenobarbitone by high-performance liquid chromatography. AB - A rapid, sensitive and accurate high-performance liquid chromatographic method for the simultaneous quantitation of phenobarbitone, phenytoin, carbamazepine and carbamazepine-10,11-epoxide in saliva is described. Only small volumes of saliva (100 microliters) are required. Separation of the drugs is achieved by reversed phase chromatography on a Nova-Pak C18 column, with a mobile phase of acetonitrile-phosphate buffer at a flow-rate of 2.0 ml/min. Detection is effected by ultra-violet absorption at 215 nm. The total run time is under 12.5 min per assay. A precipitation but no extraction step is involved, simplifying the assay method. Salivary concentrations in the range 0.25-25 micrograms/ml for carbamazepine, 0.5-20 micrograms/ml for phenytoin and phenobarbitone and 0.4-20 micrograms/ml for carbamazepine-10,11-epoxide can be measured. Recovery varies from 94 to 108%. The method has been used for routine measurements of anticonvulsants in saliva collected daily from patients with intractable epilepsy. PMID- 2592509 TI - Quantitation of homoharringtonine in plasma by high-performance liquid chromatography with amperometric detection. AB - A high-performance liquid chromatographic procedure was developed for the quantitation of homoharringtonine in plasma. Harringtonine was used as an internal standard, and 1 ml of sample was required. The single-step extraction with dichloromethane resulted in almost 100% recovery for homoharringtonine and harringtonine. Analysis was performed on a reversed-phase CN column with amperometric detection. Chromatography was completed in 12 min. At an oxidation potential of +1.0 V, the detection limit was 1 ng/ml at a signal-to-noise ratio of 2. The mean analytical recovery for homoharringtonine was 99.5%. The within run precision and between-run precision were both less than 11%. The method is equally applicable for plasma or serum, and it has been demonstrated to be applicable for study of the pharmacokinetics of homoharringtonine in patients suffering from acute non-lymphocytic leukaemia. PMID- 2592510 TI - Measurement of plasma thromboxane B2 by gas chromatography-mass spectrometry using 18O2-labelled thromboxane B2 as the internal standard. PMID- 2592511 TI - High-performance liquid chromatographic separation of urinary hippuric and o-, m- and p-methylhippuric acids with a beta-cyclodextrin-bonded column. PMID- 2592512 TI - Gas chromatographic determination of 2,3-butanediol isomers in urine. PMID- 2592513 TI - Determination of medifoxamine in plasma and urine by high-performance liquid chromatography. PMID- 2592514 TI - Determination of lofepramine and desipramine using high-performance liquid chromatography and electrochemical detection. PMID- 2592515 TI - Solid-phase extraction of furosemide from plasma and urine and subsequent analysis by high-performance liquid chromatography. PMID- 2592516 TI - Simultaneous determination of biogenic amines, their precursors and metabolites in a single brain of the cricket using high-performance liquid chromatography with amperometric detection. AB - An analytical procedure has been developed for the simultaneous determination of biogenic amines, their precursors and metabolites by high-performance liquid chromatography with amperometric electrochemical detection. Following careful adjustment of various factors involved in the separation efficiency, reversed phase chromatography with an ion-pairing technique gave simultaneous separation of nineteen biogenic amines and related substances. Peak identification was confirmed by comparison with hydrodynamic voltammograms. The method was sensitive enough to detect each substance in the picomole range. The procedure was applied to quantitate the amount of biogenic amines in a single brain of the cricket. PMID- 2592518 TI - Effect of stationary and mobile phases on hydrophobic interaction chromatography of proteins and peptides. AB - A number of different stationary phases designed for hydrophobic interaction chromatography have been examined to assess their efficiency and resolving capability with respect to protein and peptide mixtures. A packing with an ether bonded phase was substantially less hydrophobic than those with propyl- or phenyl bonded surface chemistry. While the overall efficiencies of most columns were broadly similar with respect to most proteins, some proteins did chromatograph with enhanced efficiency on specific packings. The elution order of individual proteins was, with one or two exceptions, similar for all columns tested using comparable mobile phases. It differed, however, substantially from orders obtained with conventional reversed-phase alkyl-bonded phases and from the elution orders obtained when the hydrophobic packings were used in a reversed phase mode, i.e. with an organic modifier gradient. Varying the salt used in the mobile phase and its pH under hydrophobic interaction conditions (high ionic strength) changed overall retentivities and also altered specific retention orders, thus offering possibilities of selective resolution of some mixtures. PMID- 2592519 TI - Detection of macroenzymes in serum by high-performance gel permeation chromatography. AB - A rapid high-performance gel permeation chromatographic method to confirm the presence of enzymes with abnormally high relative molecular masses (macroenzymes) in serum is described. The technique requires 200 microliters of serum, can be automated and has been implemented for the analysis of creatine kinase (CK), lactate dehydrogenase, amylase, and alkaline phosphatase (ALP) activities. Serum fractionation according to relative molecular mass is completed within 21 min, and 84-106% of enzyme activities are recovered in the eluted fractions. The elution patterns obtained make possible the differentiation of 40 samples containing at least 10 U/l immunoglobulin-enzyme complexes, aggregated mitochondrial CK or membrane fragments carrying ALP activity from 40 control samples without these high-mass enzyme forms. PMID- 2592517 TI - Multi-dimensional high-performance liquid chromatography of opioid peptides following pre-column derivatization with naphthalene-2,3-dicarboxaldehyde in the presence of cyanide ion. Preliminary results on the determination of leucine- and methionine-enkephalin-like fluorescence in the striatum region of the rat brain. AB - The reversed-phase high-performance liquid chromatography of three synthetic opioid peptides, 5leucine-enkephalin, 5methionine-enkephalin and [D-2alanine] 5methionine enkephalin, has been studied after their pre-column fluorogenic derivatization with naphthalene-2,3-dicarboxaldehyde in the presence of cyanide to the corresponding 1-cyanobenz[f]isoindole (CBI) derivatives. The chromatographic properties of the three synthetic CBI-peptides were characterized using three different stationary phases, ODS Hypersil, CPS Hypersil and Spherisorb Phenyl, eluted with mobile phases containing various concentrations of methanol, tetrahydrofuran or acetonitrile in 26 mM trifluoroacetic acid, adjusted to pH 3.5. The data obtained using single chromatographic columns were used to design a multi-dimensional system in which the three synthetic CBI-peptides of interest were transferred as a single fraction from one column to a second. The first column served to separate the peptides from the majority of the material in the samples, and the second column was used to separate the three CBI-peptides from each other. The best separation was achieved in which the first column was Spherisorb Phenyl and the second column was ODS Hypersil. Both columns were eluted with a mobile phase of 45% acetonitrile (v/v) in 26 mM trifluoroacetic acid (pH 3.5) at a flow-rate of 1.0 ml/min. The method has been applied to the determination of leucine- and methionine-enkephalin-like fluorescence in the striatum of the rat brain. PMID- 2592520 TI - Highly sensitive and specific non-radioactive biotinylated probes for dot-blot, Southern and colony hybridizations. AB - We describe a simple method for the incorporation of biotin into nucleic acid probes. This method has been improved and optimized to produce biotinylated DNA probes for the detection of DNA by dot-blot, Southern and colony hybridization techniques. The sensitivity of this method has been particularly improved to allow detection of DNA quantities under one femtogram. Probes prepared by this method are highly specific for target DNA even in crude bacterial lysates. PMID- 2592521 TI - Penicillinase-based enzyme-linked immunosorbent assay for the detection of plant viruses. AB - A penicillinase (PNC)-based, enzyme-linked immunosorbent assay (ELISA) was standardized to detect maize mosaic virus (MMV) in sorghum leaf extracts, peanut mottle virus (PMV) in pea leaf extracts, and tomato spotted wilt virus (TSWV) in peanut leaf extracts. Rabbit Fc-specific antibodies were conjugated with PNC by a single step glutaraldehyde bridge. Among several indicators tested, bromothymol blue (BTB) was found suitable for measuring PNC activity under simulated conditions. Two reagents, starch-iodine complex (SIC) and a mixed pH indicator, containing bromocresol purple and BTB (2:1) used earlier for the PNC-based ELISA, were compared with BTB for utilization in the PNC-based ELISA. SIC gave a slightly higher virus titre than BTB or the mixed pH indicator, but it often gave nonspecific reactions. Sodium or potassium salts of penicillin-G at 0.5-1.0 mg/ml and BTB at 0.2 mg/ml were found to be suitable as substrate-indicator mixture for PNC-based ELISA. The sensitivity of the PNC system was comparable to those of the alkaline phosphatase (ALP) and horseradish peroxidase (HRP) systems in detecting MMV, PMV, and TSWV. The PNC conjugate could be used at a greater dilution than those of the ALP and HRP conjugates and the BTB substrate mixture was stable for at least 3 weeks at 4 degrees C. Penicillin is readily available in developing countries, and at a substantially lower cost than p-nitrophenyl phosphate, the commonly used substrate for ALP in the plate ELISA. Thus the PNC-based ELISA provides a less expensive means for assaying plant viruses by ELISA. PMID- 2592522 TI - Rapid chemical mapping of dengue virus variability using RNA isolated directly from cells. AB - Osmium tetroxide and hydroxylamine (in combination with piperidine) have previously been shown to cleave mismatched T and C bases, respectively, in DNA.DNA heteroduplexes. In this work we report that mismatched T and C bases were similarly cleaved in DNA.RNA heteroduplexes of nucleic acids derived from different strains of dengue virus type 2. Further, some matched T or C bases one or two bases from mismatches were also chemically reactive and thus cleavable as detected by minor bands. Cleavages both at and near mismatches combined to generate a simply obtained pattern of difference between virus strains that could be used as a fingerprint of a given virus relative to another. The patterns obtained using viral RNA of one strain hybridized with the cDNA of another were similar for RNA prepared from purified virions and for total RNA extracted from infected cells. Use of probes of both senses should detect all differences. Two sequenced (NGC and PUO-218) and one unsequenced (D80-100) strains of virus were compared in these studies. The analyses allowed proof reading of the differences between NGC and PUO-218, ascertained from nucleotide sequencing, and demonstrated that D80-100 is more similar to PUO-218 than to NGC. PMID- 2592524 TI - Is neglect (only) lateral? A quadrant analysis of line cancellation. AB - We report an investigation of unilateral visual neglect in 23 patients with right cerebro-vascular accident (CVA) and 3 with left CVA. On a modified version of Albert's test of line cancellation the patients show the typical errors of omission in the hemispace contralateral to the lesion. In addition, however, there is a significant effect of stimulus position in the vertical dimension; the patients made most errors in the lower quadrant of the array, contralateral to the site of lesion. We emphasize the importance of studying the distribution of attention along all spatial dimensions in the hemispatial neglect syndromes. PMID- 2592523 TI - Assessing memory deterioration with the Wechsler Memory Scale, the National Adult Reading Test, and the Schonell Graded Word Reading Test. AB - The National Adult Reading Test (NART), the Schonell Graded Word Reading Test (SGWRT), and the Wechsler Memory Scale, Form I (WMS) were administered to 65 healthy subjects aged 65 to 89 years. Regression equations were derived which allowed total raw score on the WMS to be predicted from the subject's age and from the number of errors on the NART alone or on the NART and SGWRT combined. The distribution of discrepancies between obtained and predicted WMS scores for each equation did not depart significantly from normality and the percentage of subjects at each discrepancy score is provided. The standard error of prediction for each equation is slightly less than that for predicting WAIS IQ from the NART. Sixteen patients with clinical diagnoses of senile dementia of the Alzheimer type obtained discrepancies as large or larger than the most discrepant 2% of normal subjects. These results suggest that this procedure may provide a brief but effective assessment of cognitive deterioration in the elderly and may be capable of assessing dementia earlier than the NART/WAIS combination. PMID- 2592525 TI - Different cognitive profiles on standard behavioral tests in Parkinson's disease and Alzheimer's disease. AB - Patients with Parkinson's disease (PD) displayed a different pattern of cognitive deficit from patients with dementia resulting from Alzheimer's disease (AD). Specifically, PD patients, whether or not impaired on a mental status examination, had deficient Picture Arrangement but normal Vocabulary test scores whereas AD patients were impaired on both measures. Furthermore, PD patients with impaired mental status examination scores showed a deficit in set formation on Picture Arrangement not seen in the AD patients. Finally, when recent memory performance, as measured by the Wechsler Memory Scale, was predicted from an estimated IQ, 71% of PD patients who had normal mental status examination scores were seen to have at least a mild memory impairment. PMID- 2592526 TI - Effects of training in use of executive strategies on a verbal memory problem resulting from closed head injury. AB - This case study reports attempts to improve the recall performance of an adolescent (GC) who had suffered a closed-head injury. GC had a very limited range of ways of processing both spoken and written information and showed significant recall problems. Initial training in the use of strategies for list learning resulted in improvement in paired-associate recall but showed that initiation and use of the newly learned strategies would not occur without prompting. Executive strategy training was provided to improve GC's ability to identify a memory problem and to initiate a general plan for dealing with that problem. This training involved consideration of task analysis, strategy selection and initiation, and monitoring of strategy use. Evidence of long-term maintenance of improvement in level of recall on both paired-associate and free recall tests was noted following the executive strategy training. PMID- 2592527 TI - The development and validation of a test battery for detecting and monitoring everyday memory problems. AB - This paper describes the Rivermead Behavioural Memory Test (RMBT)-a short test of everyday memory problems with four parallel forms. It was administered to 118 control subjects aged between 16-69 years with a mean IQ of 106 (range 68-136). The limit of normal performance was established on this group and cut-off points were determined for individual components of the test. The test was also given to 176 brain-damaged people and its validity assessed both by correlating RMBT scores to performance on existing tests, to subjective ratings from patients and carers and to observation by therapists of memory lapses. Validity, parallel form and interrater reliability all proved to be high. It is concluded that the RBMT is a short, reliable, and valid test of everyday memory problems. PMID- 2592528 TI - Training use of compensatory memory books: a three stage behavioral approach. AB - A systematic, structured training sequence for teaching individuals with severe memory impairments to independently utilize a compensatory memory book is reviewed. The training sequence is theoretically motivated, incorporating both principles of learning theory as well as aspects of memory known to be preserved in many patients with even severe amnestic disorders. This paper describes the components of a functional memory book system as well as the three-stage behavioral training procedure. An illustrative case study reviewing the training and resultant effective use of a memory book system for daily living and employment in a severely memory-impaired patient is provided. PMID- 2592529 TI - The WAIS-R profile: a diagnostic tool for Alzheimer's disease? AB - A diagnostic index, based on WAIS-R subtests, to identify patients with Dementia of the Alzheimer Type (DAT) and differentiate them from normal or depressed elderly was investigated. In a sample of 82 geriatric outpatient clinic patients who complained of memory loss, 22% of patients with probable DAT and 13% of nondemented patients obtained a positive profile. The occurrence of the profile in the two groups was not significantly different, nor were differences in education or severity of dementia found between subjects who did or did not obtain the profile. In a second sample of 173 elderly research volunteers, the profile occurred in 7% of DAT subjects, 10% of subjects complaining of memory loss who did not meet diagnostic criteria for DAT, 7% of nondemented major depressed subjects, and 7% of normal control subjects. Thus, the current investigation did not find the profile useful in differentiating DAT from other common disorders among elderly subjects. The authors conclude that a more comprehensive test battery remains the diagnostic tool of choice for differentiating DAT from other disorders. PMID- 2592531 TI - Changes in cerebral functioning associated with normal aging. AB - It has been suggested that the normal aging process is characterized by a pattern of neuropsychological performance decline that implies relatively greater vulnerability of right-hemisphere functions. This hypothesis was tested in a sample of 68 volunteers aged 20-75 who were free of systemic and neurologic illness. Neuropsychologic measures of lateralized and focal function were specifically selected to eliminate systematic procedural differences among tests (e.g., timed vs. untimed, overlearned vs. unfamiliar). Inferences about the localizing significance of each measure were based on previously demonstrated double dissociation of function in lesion studies. Results suggested that declines in cerebral efficiency are not differentially lateralized. Age correlated performance changes implied bilateral reduction that was significantly more pronounced on operations associated with frontal-lobe function. Anatomic and theoretical explanations for this pattern were discussed. PMID- 2592530 TI - Tinker toy test performance and vocational outcome in patients with closed-head injuries. AB - Fifty patients who had suffered closed-head injury with no resultant physical disabilities and 25 normal controls were administered a modified version of Lezak's Tinker Toy Test. All head-injured patients were examined at least 24 months following medical clearance to return to work. Twenty-five of the head injured had been unable to return to work or sustain normal competitive employment as a result of their head injuries. The remaining 25 had returned to their previous jobs successfully or had been employed for at least 6 months prior to assessment. Whereas all but one of the head injured who returned to work scored normally on the Tinker Toy Test, nearly half of the nonreturnees performed below the level of the worst control. PMID- 2592532 TI - Neuropsychological effects of occupational exposure to cadmium. AB - Neuropsychological functioning was measured in 31 male workers exposed to cadmium in a refrigerator coil manufacturing plant. Workers with high urinary cadmium levels performed less well than did those with low urinary cadmium levels on measures of attention, psychomotor speed, and memory. There were modest correlations between one of two biologic measures of cadmium exposure and neuropsychological performance. The neuropsychological impairments cannot readily be attributed to exposure to other neurotoxins, alcohol intake, CNS effects of renal dysfunction, or psychological distress. Cadmium body burden has previously been related to intelligence and school achievement of children; this study would appear to be the first to suggest that occupational exposure to cadmium is associated with cognitive impairment in adults. Cadmium interferes with several important nervous system functions, but the mechanisms of neurotoxicity remain uncertain. PMID- 2592533 TI - For better or for worse: left-handedness, pathology, and talent. AB - Geschwind and his colleagues have hypothesized that left-handedness may be a marker for anomalous dominance and is associated with certain immune disorders, learning disorders, and special talents. The few relevant studies done to date have yielded somewhat mixed findings, and little had been done to study the relationship of relevant findings to the definition of handedness employed in a given study. The present study assessed the association between handedness and a variety of disorders, talents, and skills in subjects and their parents and siblings. Results showed that mathematical, artistic, and musical talents varied systematically as a function of handedness. Verbal skills, stuttering, and asthma were also significant discriminators in some discriminant function analyses, and certain variations in the definition of handedness produced systematic variations in results. Finally, certain disorders, particularly eczema, stuttering, and epilepsy, in the parents were related to handedness in their offspring. PMID- 2592534 TI - Demonstration of savings on the AVLT and development of a parallel form. AB - The purposes of the present study were (1) to investigate whether significant savings occur with repeat testing on Rey's Auditory-Verbal Learning Test and (2) to develop a parallel version of the AVLT. Subjects (N = 60) were divided into pairs (individually matched for sex, age, and education) to form two groups and were administered either the AVLT or a parallel version. Results indicated no significant differences on all AVLT measures of learning, recall, and recognition, suggesting that the parallel version can be used as an equivalent form of the AVLT. Subjects were retested after an interval of 27 (+/- 3) days, with half receiving the same version and half receiving a different version. In contrast to subjects receiving different lists, those who were retested with the same version demonstrated a significant improvement in performance on the majority of AVLT variables. PMID- 2592535 TI - Systemic and local antibody responses in elderly subjects given live or inactivated influenza A virus vaccines. AB - Intranasal live attenuated cold-adapted (ca) influenza A/Kawasaki/9/86 (H1N1) reassortant virus and parenteral inactivated influenza A/Taiwan/1/86 (H1N1) virus were given alone or in combination to 80 ambulatory elderly subjects. An enzyme linked immunosorbent assay was used to measure hemagglutinin-specific (HA) antibodies in serum and nasal wash specimens collected before vaccination and 1 and 3 months later. Serum immunoglobulin G (IgG) and nasal wash IgA HA responses were elicited in 56 and 20%, respectively, of 25 inactivated-virus vaccinees and in 67 and 48%, respectively, of 27 recipients of both vaccines but in only 36 and 25%, respectively, of 28 vaccinees given live virus alone. Inactivated virus, administered alone or with live virus vaccine, induced higher titers of serum antibody than did the live virus alone. In contrast, nasal IgA HA antibody was elicited more often and in greater quantity by the vaccine combination than by either vaccine alone. Despite these differences, the peak titers of local antibody mounted by each group of vaccinees were similar. By 3 months postvaccination, serum IgG and nasal IgA HA antibody titers remained elevated above prevaccination levels in 50 and 17%, respectively, of the inactivated-virus vaccinees and in 46 and 23%, respectively, of recipients of both vaccines but in only 19 and 7%, respectively, of the live-virus and systemic antibodies, if vaccinees. The finding that live ca influenza A virus induced short-lived local and systemic antibodies, if confirmed, suggests that live virus vaccination may not be a suitable alternative or adjunct to inactivated virus vaccination for the elderly. PMID- 2592536 TI - Acinetobacter baumannii serotyping for delineation of outbreaks of nosocomial cross-infection. AB - A total of 152 clinical isolates of Acinetobacter baumannii from 152 patients were identified by carbon source utilization tests and examined serologically. Polyclonal rabbit immune sera against A. baumannii strains were used in checkerboard tube agglutination tests, and 20 serovars were identified. One (serovar 19) cross-reacted with genospecies 3 (serovar 3), a closely related member of the genus Acinetobacter. Several outbreaks of nosocomial cross infection caused by serovars 4 and 10 were delineated. PMID- 2592537 TI - Species-specific cloned DNA probes for the identification of Campylobacter hyointestinalis. AB - Conventional microbiological methods for isolating and identifying Campylobacter species are laborious, tedious, and subjective. Because of the increasing importance of Campylobacter species in human and animal diseases and the recent emergence of many new species and atypical strains, we are developing chromosomal DNA probes for rapid and simple identification of Campylobacter species, especially those of veterinary importance. We report the cloning and characterization of chromosomal DNA fragments from Campylobacter hyointestinalis, an organism isolated from pigs with proliferative enteritis. To obtain C. hyointestinalis-specific probes, chromosomal DNA fragments from C. hyointestinalis were cloned into plasmid vector pGEM-3Z. Recombinant plasmids were screened for C. hyointestinalis-specific inserts by DNA hybridization, using chromosomal DNA from either C. hyointestinalis or C. fetus which had been 32P labeled. Recombinants which hybridized to C. hyointestinalis, but not C. fetus, DNA were 32P labeled and screened further for sensitivity and specificity. Three probes were identified that were species specific and capable of detecting 10(4) C. hyointestinalis organisms by bacterial spot blotting in 48 h. We anticipate that these probes will be useful for routine species identification and for epidemiological studies. PMID- 2592538 TI - Cloned DNA probes identify Anaplasma ovis in goats and reveal a high prevalence of infection. AB - Anaplasma organisms are observed in erythrocytes from goats with anemia and weight loss in Kenya. Three anaplasmas have been isolated in nature, Anaplasma ovis, Anaplasma marginale, and Anaplasma centrale. The two recognized species, A. ovis and A. marginale, are known to infect goats. Since only A. ovis causes clinical disease in goats, the Anaplasma species in goats in Kenya were identified. To detect A. ovis, a 9.6-kilobase-pair section of genomic DNA was cloned into pBR322 (pAO12A) and was used in conjunction with an A. marginale DNA probe previously derived from a gene coding for a 105,000-molecular-weight surface protein (Am105L) of A. marginale. In Southern blots, pAO12A DNA hybridized to several at least partially homologous sequences that were present in A. ovis and A. marginale genomic DNAs. The pAO12A DNA did not hybridize to Babesia bovis genomic or goat leukocyte DNA. The Anaplasma species that infected goats was identified as A. ovis by (i) DNA hybridization with pAO12A, (ii) hybridization of the A. marginale DNA probe to A. centrale and A. marginale genomic DNAs and lack of hybridization to A. ovis genomic DNA from an isolate obtained in Idaho and Anaplasma DNA from infected goats in Kenya, (iii) the intraerythrocytic location of Anaplasma organisms in infected goat blood, and (iv) the host specificity of the Anaplasma organisms for goats but not for cattle. Also, by using the two Anaplasma DNA probes, the prevalence of A. ovis in goats from seven locations in Kenya was found to range from 22 to 87%. The pAO12A DNA probe detected a 0.0035% A. ovis parasitemia in infected blood, an improved sensitivity which is suitable for use in surveillance and epidemiological studies. PMID- 2592539 TI - Comparison of the nasal bacterial floras in two groups of healthy subjects and in patients with acute maxillary sinusitis. AB - The nasal bacterial flora was studied in 183 healthy men entering military service (entry group), 103 healthy recruits in service (service group), and 185 recruits with acute maxillary sinusitis. The 267 nasal and ipsilateral sinus aspirate findings in the same patients with acute maxillary sinusitis were compared pairwise. In the entry group presumed sinus pathogens were only rarely isolated from the nasal cavities: Haemophilus influenzae in 4%, Streptococcus pneumoniae in 1%, Branhamella catarrhalis in 3%, and Streptococcus pyogenes in 0%. The corresponding isolation frequencies in the service group were 19, 13, 3, and less than 1%, respectively, and those in the group with acute maxillary sinusitis were 61, 25, 7, and 6%, respectively. Suppression of the major components of the normal nasal flora, Corynebacterium sp., coagulase-negative staphylococci, Propionibacterium acnes, and Staphylococcus aureus, was seen in the group with acute maxillary sinusitis and also occasionally in the service group. When a sinus aspirate culture yielded a presumed sinus pathogen, the same pathogen was found in the nasal samples in 91% of the cases. The predictive value of a pathogen-positive nasal finding was highest (93.8%) for S. pyogenes, followed by 77.7% for H. influenzae and 68.7% for S. pneumoniae, and lowest (20%) for B. catarrhalis. PMID- 2592540 TI - Enzyme immunoassay to determine exposure to Chlamydia pneumoniae (strain TWAR). AB - Recent studies suggest that a group of Chlamydia strains known as TWAR, which are now proposed to be a new species called Chlamydia pneumoniae, may be a frequent cause of respiratory disease in the United States and many other countries. Current serotesting methods do not allow rapid screening of large numbers of samples to distinguish C. trachomatis exposure from C. pneumoniae exposure. We developed an enzyme immunoassay to decrease cross-reactivity between immunoglobulin G antibodies reactive with C. trachomatis and C. pneumoniae. Elementary bodies of C. trachomatis or C. pneumoniae were treated with a detergent-chelating solution to decrease the reactivity of the common lipopolysaccharide antigens. Sera from four groups of patients, totaling 143 persons, were tested by this assay. The prevalences of titers of greater than or equal to 128 to C. trachomatis and C. pneumoniae, respectively, were as follows: (i) for 23 women seropositive for C. trachomatis by the microimmunofluorescence test, 21 (91%) and 18 (78%); (ii) for 50 adult blood donors, 13 (26%) and 39 (78%); (iii) for 40 sexually transmitted disease clinic patients, 20 (50%) and 32 (80%); (iv) for 30 healthy children 5 to 7 years old, 0 (0%) and 8 (27%). Western blots (immunoblots) of each antigen corroborated the differential reactivity of C. trachomatis-positive, C. pneumoniae-negative and C. trachomatis-negative, C. pneumoniae-positive serum samples. Western blots of serum samples from rabbits immunized with either C. trachomatis or C. pneumoniae elementary bodies revealed at least two protein bands (30 and 80 kilodaltons) which appeared to represent unique C. pneumoniae antigens. PMID- 2592541 TI - Rapid screening for Staphylococcus aureus infection by measuring enterotoxin B. AB - We developed a simple, sensitive laser nephelometric assay (LNA) to detect circulating staphylococcal enterotoxin B (SEB). This assay yields the result within 2 h and needs no special treatment. Influence of protein A, a product generated by Staphylococcus aureus, was negligible in this assay. The levels of SEB in plasma were measured in 28 patients with and without S. aureus infection with the LNA. The levels of SEB in plasma increased significantly in patients with S. aureus infection. We also demonstrated that the levels of SEB in plasma were higher in patients with methicillin-resistant S. aureus infection than in patients with nonresistant staphylococcal infection. Our data indicate that LNA is a useful assay in the early diagnosis of methicillin-resistant S. aureus infection. PMID- 2592542 TI - TestPack Chlamydia, a new rapid assay for the direct detection of Chlamydia trachomatis. AB - TestPack Chlamydia (Abbott Laboratories) is a rapid enzyme immunoassay for the direct antigen detection of Chlamydia trachomatis in endocervical specimens. The assay is self-contained, requires no specialized equipment, and yields results in less than 30 min. The clinical performance of TestPack Chlamydia versus chlamydial cell culture was evaluated with a total of 1,694 paired endocervical specimens. Discordant samples were further investigated by immunofluorescent staining and by Chlamydiazyme immunoassay, with confirmatory procedures. The sensitivity of TestPack Chlamydia with less-than-48-h-old specimens was 76.5%, while culture sensitivity was 86.7%. TestPack Chlamydia specificity was determined to be 99.5%. These results indicate that TestPack Chlamydia is an accurate test for chlamydial infection, with a positive predictive value of 96.2%. This assay is suitable for low-volume chlamydial testing in physician offices, clinics, and smaller laboratories. PMID- 2592543 TI - Urease-positive, Kanagawa-negative Vibrio parahaemolyticus from patients and the environment in the Pacific Northwest. AB - We previously reported the occurrence of Vibrio parahaemolyticus in patients and the environment in the Pacific Northwest. The present studies compare the biochemical characteristics, Kanagawa hemolysin reactions, and plasmid profiles of 13 patient and 221 environmental isolates of the organism. Classical biochemical testing of the isolates revealed similar reactions for the clinical and environmental strains, and analysis in agarose gels revealed that 13 to 15% of the isolates had plasmids. The strains were tested for production of Kanagawa hemolysin on Wagatsuma agar, and 1.4% of environmental isolates and 23% of clinical isolates were positive. Clinical isolates from locally acquired extraintestinal infections were urease negative and Kanagawa hemolysin negative, isolates from locally acquired gastroenteritis cases were urease positive and Kanagawa negative, and isolates from traveler's diarrhea were urease negative and Kanagawa positive. Eight percent of the local environmental isolates were also urease positive and Kanagawa hemolysin negative. These findings suggest that expression of the Kanagawa hemolysin is not essential for the pathogenesis of V. parahaemolyticus infections. In addition, our findings suggest that V. parahaemolyticus gastroenteritis in the Pacific Northwest is associated with a urease-positive, Kanagawa-negative biotype of the organism. PMID- 2592544 TI - Detection of the 43,000-molecular-weight glycoprotein in sera of patients with paracoccidioidomycosis. AB - The 43,000-molecular-weight (43K) soluble glycoprotein was detected in sera of patients with paracoccidioidomycosis by the immunoblot technique by using as the probe rabbit monospecific antisera to this fraction. The 43K antigen was present before treatment in sera of patients with the acute (juvenile) form; it started to disappear from circulation after 10 months of chemotherapy, and it was undetectable after 2 years of treatment. In the chronic cases, the 43K antigen was detected in patients without treatment, and it was absent in the healed cases. The detection of the 43K protein specific to Paracoccidioides brasiliensis may be important for its diagnostic value as well as for modulation of the host immune response. PMID- 2592545 TI - Evidence for the occurrence of the same strain of Campylobacter pylori in the stomach and dental plaque. AB - Restriction endonuclease analysis with HindIII, HaeIII, and BglII endonucleases of DNA extracted from each of eight colonies of Campylobacter pylori subcultured from a stomach biopsy and from each of eight colonies subcultured from dental plaque of the same patient indicated that at least three strains were present in the dental plaque but only one strain was present in the biopsy. One of the dental strains had restriction patterns indistinguishable from those of the biopsy isolate, providing evidence that both sites were infected with the same strain of C. pylori. PMID- 2592546 TI - Unusual non-serogroup O1 Vibrio cholerae bacteremia associated with liver disease. AB - A 50-year-old woman and a 31-year-old man with underlying liver disease presented with fever and signs of liver failure. The blood cultures in both cases yielded non-serogroup O1 Vibrio cholerae strains which were biochemically identical except that one strain was nonmotile. Despite treatment with antibiotics, the older patient died; the other patient survived. Both strains were found to be susceptible to most antibiotics tested in vitro. No apparent source of infection could be identified in either case. PMID- 2592547 TI - Novel latex agglutination method with chicken anti-protein A for detection of Staphylococcus aureus infections. AB - A latex agglutination assay for the detection of protein A-secreting Staphylococcus aureus strains or strains with protein A in the cell wall is described. The assay utilizes latex particles coated with chicken anti-protein A antibodies. Chicken antibodies do not react with protein G-producing streptococci or rheumatoid factor, thus avoiding false-positive reactions. PMID- 2592548 TI - Temafloxacin disk potency and tentative interpretive criteria for susceptibility tests. AB - Temafloxacin disk susceptibility test criteria were evaluated by testing 697 bacterial isolates. Either 5- or 10-micrograms disks could be used satisfactorily. A 5-micrograms temafloxacin disk with zone size breakpoints of less than or equal to 12 mm for resistance (MIC, greater than 4.0 micrograms/ml) and greater than 16 mm for susceptibility (MIC, less than or equal to 2.0 micrograms/ml) is recommended. PMID- 2592549 TI - Corynebacterium xerosis as a cause of vertebral osteomyelitis. AB - We report a patient who developed Corynebacterium xerosis vertebral osteomyelitis 6 months following a decompressive laminectomy. Prolonged parenteral and subsequent oral therapy for 11 months resulted in apparent cure. This is the first reported case of vertebral osteomyelitis caused by C. xerosis. PMID- 2592550 TI - Bacteremic cellulitis caused by non-serogroup O1 Vibrio cholerae acquired in a freshwater inland lake. AB - The number of reported cases of infections with non-serogroup O1 Vibrio cholerae in the United States has increased recently. These cases have almost invariably been associated with travel, seawater exposure, or the ingestion of shellfish. We report a case of bacteremic cellulitis caused by non-O1 V. cholerae that was acquired in a freshwater inland lake in northern Illinois. The organism is more widely distributed than generally appreciated, and the potential for infection in patients without the usual risk factors exists. PMID- 2592551 TI - Urinary tract infection caused by Enterobacter taylorae. AB - We present a case of urinary tract infection caused by Enterobacter taylorae in a 70-year-old male with renal lithiasis. The microorganism was isolated in significant numbers from a urine culture. The disappearance of clinical symptoms after antibiotic treatment points to the participation of this microorganism as the etiological agent in the infection. PMID- 2592552 TI - Prospective survey of colonization and infection caused by expanded-spectrum-beta lactamase-producing members of the family Enterobacteriaceae in an intensive care unit. AB - The occurrence of expanded-spectrum-beta-lactamase-producing strains was prospectively studied in 56 patients in an intensive care unit. Ten patients were infected or colonized; some of these patients had asymptomatic intestinal colonization. Four different expanded-spectrum beta-lactamases were identified and used as epidemiological markers to survey nosocomial infections. PMID- 2592553 TI - Emergence of a restricted bioserovar of Vibrio parahaemolyticus as the predominant cause of Vibrio-associated gastroenteritis on the West Coast of the United States and Mexico. AB - Examination of 45 human fecal isolates of Vibrio parahaemolyticus revealed the emergence of an unusual bioserovar (O4:K12, urease positive) associated with cases of gastroenteritis which appear to be domestically acquired on the West Coast of the United States and Mexico. PMID- 2592554 TI - Slip of rabbit striated muscle in rigor or AMPPNP. AB - Single glycerol-extracted rabbit psoas muscle fibres have been slowly extended either in rigor or in the unhydrolysable ATP analogue, AMPPNP, and their sarcomere length, sarcomere structure and tension measured. The length of regularly arrayed sarcomeres, measured by optical diffraction, increased continuously as the muscle was stretched; the maximum sarcomere extension seen was approximately 6%. In the electron microscope sarcomeres from extended muscle fixed in rigor or AMPPNP remained regular in their internal structure, without rupture or obvious lengthening around the Z line. During steady extension at 0.024% per min the tension in the muscle fibre rose until it reached a limiting value [Tm] when the sarcomeres had stretched by 0.8-1.6% and then remained constant with continued extension, while the sarcomeres continued to stretch. Provided that a novel form of preparation of the glycerol-extracted fibres was employed, Tm in rigor was a large fraction of the tension expected from an active isometric muscle fibre. In the presence of AMPPNP Tm was reduced by a factor of 2 to 3. Step extension by 0.08% at 5-min intervals gave the same pattern of mechanical response with similar values of Tm. The isometric tension decay in the interval between the steps was very rapid at first and slowed continuously until the next step. The average speed of tension fall between 30 and 300 s after stretch was measured at each step and plotted relative to the tension in the muscle. The relationship approached linearity, although with a significant upward curvature at high tension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592556 TI - Modelling fibre kinetics. PMID- 2592555 TI - Size and charge heterogeneity of C-protein isoforms in avian skeletal muscle. Expression of six different isoforms in chicken muscle. AB - C-protein is an abundant protein, of unknown function, found in the striated muscles of all vertebrates (Offer et al., 1973). Based on differences in size, charge, antigenicity and sarcomere distribution, at least three different isoforms of this protein have been identified (Callaway & Bechtel, 1981; Yamamoto & Moos, 1983; Reinach et al., 1982; Dhoot et al., 1985). These have been termed fast-, slow- and cardiac-type isoforms, relative to their distribution in adult striated muscles. Each of these isoforms appears to be expressed sequentially during the development of the chicken pectoralis muscle (Obinata et al., 1984; Obinata, 1985). To better characterize the various isoforms of C-protein, we have reexamined its in vivo expression during avian myogenesis using a combination of 1- and 2-dimensional gel electrophoresis, cell-free translation and immunoblotting procedures. In this manuscript we demonstrate for the first time that at least four major C-protein isoforms can be distinguished in adult chicken muscles. These include a fast-type isoform in the pectoralis (PECT) muscle (Cf), a slow-type isoform in the anterior latissimus dorsi (ALD) muscle (Cs3), a second slow-type isoform in the posterior latissimus dorsi (PLD) muscle (Cs4) and a cardiac-type in the ventricle (Cc). During embryonic development of the PECT muscle two additional isoforms can be resolved. These are both slow-type isoforms based on their reactivities with ALD66, a monoclonal antibody specific for adult slow-type C-protein. These latter isoforms have been termed Cs1 and Cs2. Several of the isoforms, particularly Cs1 ands Cs3, exhibit two or more spots of different charge but identical molecular weight on 2-D gels. This observation suggests the possibility that these isoforms are post-translationally modified and possibly phosphorylated. Our data show the C-protein family in avian striated muscles to be highly complex. Additional genetic analyses and primary sequence studies will be required to distinguish transcriptional from post-transcriptional variants. PMID- 2592557 TI - The reactivity of desmosterol and other shellfish- and xanthomatosis-associated sterols in the macrophage sterol esterification reaction. AB - The acyl-CoA: cholesterol acyl transferase (ACAT) reaction in macrophages is a critical step in atherosclerotic foam cell formation, but little is known about the reaction's sterol substrate specificity. In this report we examine the macrophage ACAT reactivity of the shellfish sterol, desmosterol, and other sterols found in man because of shellfish ingestion or in association with the foam cell diseases sitosterolemia and cerebrotendinous xanthomatosis (CTX). We first show that the J774 macrophage, a foam cell model with a hyperactive ACAT pathway, synthesizes desmosterol instead of cholesterol and that both endogenous and exogenous desmosterol are substrates and stimulators of the ACAT reaction in these cells. When exogenous desmosterol was added to human monocyte-derived macrophages, ACAT was stimulated 29- and 4-fold compared with control and cholesterol-treated cells, respectively. Steryl ester mass accumulation in desmosterol-treated human macrophages was 10-fold greater than in control cells and 3-fold greater than in cholesterol-treated cells. Another shellfish sterol, 24-methylene cholesterol, also stimulated ACAT in human macrophages, but most of the xanthomatosis-related sterols did not stimulate ACAT. These data suggest that: (a) the shellfish sterols desmosterol and 24-methylene cholesterol may be atherogenic; and (b) the excessive foam cell formation seen in sitosterolemia and CTX cannot be explained by ACAT hyperreactivity of their associated sterols. PMID- 2592558 TI - Genetic and environmental factors that regulate cytosolic epoxide hydrolase activity in normal human lymphocytes. AB - To determine whether genetic mechanisms control large variations in cytosolic epoxide hydrolase (cEH) activity of unstimulated lymphocytes from normal human subjects, cEH activity was measured in (a) 6 sets of monozygotic (MZ) twins and 6 sets of dizygotic (DZ) twins; (b) 100 unrelated male subjects; and (c) 6 families. The twin study revealed predominantly genetic control (H2(1) = 0.95). Variability was markedly less within MZ (intrapair variance = 0.25) than DZ twins (intrapair variance = 6.33). In 100 unrelated male subjects the extent of interindividual variation was 11-fold. Unimodal distribution of values among 99 subjects encompassed a sixfold range. One outlier with very high activity clearly stood apart. Using the whole distribution curve we phenotyped members of six families. In the outlier's family, analysis of three generations suggested autosomal dominant transmission of high cEH activity. Analysis of the other 5 families and of 12 sets of twins, all from the large unimodal distribution, was consistent with either monogenic or polygenic control of variations within this mode. Several temporal host factors, including fever, the menstrual cycle, a 24-h fast, and diurnal variations, were investigated. Fever and fasting elevated cEH activity. Diurnal variations produced no observable alteration. During the menstrual cycle irregular fluctuations occurred. PMID- 2592559 TI - Epidermal growth factor enhances renal tubule cell regeneration and repair and accelerates the recovery of renal function in postischemic acute renal failure. AB - To determine the timing and location of renal cell regeneration after ischemic injury to the kidney and to assess whether exogenous epidermal growth factor (EGF) enhances this regenerative repair process to accelerate recovery of renal function, experiments were undertaken in rats undergoing 30 min of bilateral renal artery clamp ischemia followed by reperfusion for varying time intervals. Renal cell regeneration, as reflected by incorporation of radiolabeled thymidine within the kidney, began between 24 to 48 h and reached a peak at 72 h after renal ischemia. As demonstrated by histoautoradiography, renal thymidine incorporation was essentially confined to tubule cells. Morphometric analysis of histoautoradiograph sections of renal tissue demonstrated that the majority of labeled cells were found in renal cortex, but some labeled cells were also located in the inner stripe of the outer medulla, suggesting that injury to medullary thick ascending limbs also occurs in this ischemic model. Exogenous EGF administration produced increases in renal thymidine incorporation compared with non-treated animals at 24, 48, and 72 h after ischemic injury. This accelerated DNA replicative process was associated with significantly lower peak blood urea nitrogen (BUN) and serum creatinine levels, averaging 63 +/- 20 and 3.1 +/- 0.4 mg/dl in EGF-treated ischemic rats compared with 149 +/- 20 and 5.1 +/- 0.1 mg/dl, respectively, in nontreated ischemic rats, and was also associated with a return to near normal BUN and serum creatinine levels in EGF-treated animals approximately 4 d earlier than that observed in nontreated animals. This report is the first demonstration that EGF accelerates the repair process of a visceral organ after an injurious insult. PMID- 2592560 TI - Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells. AB - In vitro and in vivo studies suggest that liver fat-storing cells (FSC) may play an important role in the development of liver fibrosis. We explored the effects of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and TGF-beta, and basic fibroblast growth factor (bFGF) on DNA synthesis and growth of rat liver FSC. PDGF, EGF, TGF-alpha, and bFGF induced a dose-dependent increase in DNA synthesis with a peak effect at 24 h. PDGF produced the most striking effect with a maximum 18-fold increase over control. EGF, TGF-alpha, and bFGF elicited a maximum three- to fourfold increase in DNA synthesis. Analysis of growth curves revealed a similar pattern of potency of the growth factors. TGF-beta did not affect DNA synthesis of FSC; however, TGF beta markedly potentiated the stimulatory effects of both EGF and PDGF. FSC showed high specific binding of 125I-PDGF and Scatchard analysis revealed high affinity receptors with an apparent Kd of 2.3 x 10(-10) M. Our data suggest that PDGF is a key mitogen for FSC and that the coordinate release of other growth factors together with PDGF by inflammatory cells represents a potent potential stimulus for FSC proliferation in conditions of chronic self-perpetuating liver inflammation. PMID- 2592562 TI - Developmental and hormonal regulation of glucocorticoid receptor messenger RNA in the rat. AB - The biological action of glucocorticoids is dependent upon tissue-specific levels of the glucocorticoid receptor (GR). During stress, the hypothalamic-pituitary adrenal axis is stimulated, and high levels of glucocorticoids circulate. This axis is modulated by negative feedback by glucocorticoids, which inhibit hypothalamic and pituitary hormone secretion and downregulate GR gene expression. To study the developmental tissue-specific regulation of the GR, we measured the relative concentration of GR mRNA in fetal, neonatal, adult, and aged rats and examined the effects of dexamethasone on GR gene expression. Three different tissue-specific developmental patterns of GR mRNA accumulation were found. In addition, there was an age-dependent tissue-specific pattern in the feedback regulation of GR mRNA by glucocorticoids. In the fetus and neonate, GR mRNA abundance was not regulated by circulating glucocorticoids. The adult pattern of glucocorticoid feedback inhibition of GR mRNA expression appeared between 2 and 7 d of life in liver, and after 7 but before 14 d of age in brain. The GR was biologically active in the 2-d-old neonate, however, since dexamethasone enhanced gene expression of angiotensinogen, which is another glucocorticoid responsive gene. These data demonstrate that the GR gene is regulated by both developmental and tissue-specific factors, and provide another molecular basis for ontogenic variations in the hypothalamic-pituitary-adrenal response to stress. PMID- 2592561 TI - Human mannose-binding protein activates the alternative complement pathway and enhances serum bactericidal activity on a mannose-rich isolate of Salmonella. AB - The human mannose-binding protein (MBP) is a multimeric serum protein that is divided into three domains, a cysteine-rich NH2-terminal domain that stabilizes the collagen alpha helix of the second domain and a third COOH-terminal carbohydrate recognition domain. Previous studies have shown that both native and recombinant human MBP bind to wild-type virulent Salmonella montevideo that expresses a mannose-rich lipopolysaccharide. Interaction with MBP results in opsonization and killing by phagocytes. In this report we show that low concentration of MBP (less than 10 micrograms/ml) markedly enhance complement deposition via the alternative complement pathway on S. montevideo. Despite structural similarities between MBP and the C1q subcomponent of the first complement component, MBP did not restore classical pathway activity to C1q deficient serum, nor did it activate C1s when added to a mixture of C1r and C1s. In the presence of MBP the C3 bound to S. montevideo during incubation in serum was in the form of C3b and iC3b at a ratio of 1:2. Presensitization of S. montevideo with MBP rendered this normally serum resistant organism susceptible to complement-mediated killing. These results emphasize that MBP and complement cooperate in first line defense of the nonimmune host. PMID- 2592563 TI - Ovarian failure and autoimmunity. Detection of autoantibodies directed against both the unoccupied luteinizing hormone/human chorionic gonadotropin receptor and the hormone-receptor complex of bovine corpus luteum. AB - We developed an ELISA system for the detection of human anti-ovarian antibodies. Bovine corpora lutea were extracted in PBS (pH 7.2) and fractionated by ultracentrifugation. Both the soluble fraction obtained after 80,000 g (S80) and the Triton-extracted membrane fraction (ST288) were used as antigens. Additionally, the luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor was isolated by affinity chromatography (wheat germ agglutinin and LH Sepharose) and also used as an antigen. In 7 of 14 patients with primary sterility and endometriosis a positive reaction was observed. Similarly, 6 of 16 patients with secondary sterility and endometriosis were also positive. Patients being stimulated for in vitro fertilization and presenting either primary or secondary sterility were positive in 5 of 22 and 6 of 16 cases, respectively. In the S80 test 41 of 60 sera presented IgG2 antibodies, whereas in the ST288 test 38 of 60 belonged to the IgG1 subclass. Kappa and lambda chains were equally distributed. Some patients could recognize the unoccupied LH/hCG receptor as an antigen, while others recognized only the complex formed by the hormone plus the hormone receptor. The S80 and ST288 antigens were isolated by affinity chromatography. Gel permeation of the purified antigens revealed in each case the presence of an antigen complex. The apparent molecular weight was between 2,000 and 36,000 D. Cross-reactivity studies using affinity-purified antibodies demonstrated an antigenic relationship of the membrane, soluble, and extractable fractions. NAc-(beta-1----4)-D-glucosaminide and -D-galactopyranoside were the main terminal glycosides. PMID- 2592564 TI - Ambient C1- ions modify rat mesangial cell contraction by modulating cell inositol trisphosphate and Ca2+ via enhanced prostaglandin E2. AB - Our recent observation showed that angiotensin II (AII) and arginine vasopressin (AVP) stimulate Ca2+-activated Cl- conductance in mesangial cells. These data raise the possibility that mesangial cell function may be modulated by extracellular chloride concentration [( Cl-]o). The present study was undertaken to test this possibility using cultured rat mesangial cells. When the [Cl-]o was reduced to zero, the percentage of mesangial cells showing contraction responding to AII and AVP was decreased from 72 +/- 9 to 33 +/- 10% and from 60 +/- 4 to 24 +/- 11%, respectively. Ca2+ transients induced by AII and AVP, measured in mesangial cells loaded with Ca2+-sensitive photoprotein aequorin, were attenuated as [Cl-]o decreased. Also, when [Cl-]o decreased, inositol trisphosphate (IP3) levels of mesangial cells were suppressed, both in the presence and absence of AII or AVP. PGE2 production by mesangial cells increased when [Cl-]o decreased and the effects of ambient Cl- deprivation could be restored by addition of indomethacin to the Cl- -free medium. Moreover, PGE2 decreased mesangial cell contractility, Ca2+ transients, and IP3 production in response to AII and AVP. These data suggest that the decrease in [Cl-]o attenuates mesangial cell contraction by suppressing IP3 production and thus Ca2+ transients in response to AII and AVP through enhanced PGE2 production. PMID- 2592565 TI - Quantitative contribution of systemic vascular autoregulation in acute hypertension in conscious dogs. AB - Experiments were performed in nine conscious dogs to quantitate the contribution of systemic vascular autoregulation to the increases in total peripheral resistance (TPR) and mean arterial pressure (MAP) produced by angiotensin II (ANG II), arginine vasopressin (AVP), and norepinephrine (NE). We hypothesized that if autoregulatory vasoconstriction is significant, then the increase in TPR produced by vasoconstrictor infusion will be greater when MAP is controlled at hypertensive values than when the increase in pressure is prevented by controlling MAP at the animal's normotensive value. Each drug was infused at a dose sufficient to increase MAP by 50%. Then, a constant rate of vasoconstrictor infusion was maintained while MAP was controlled at hypertensive or normotensive levels for 15-min periods using a gravity reservoir connected to the left common carotid artery. During AVP infusion, TPR was significantly greater when MAP was controlled at hypertensive than at normotensive values. This autoregulatory mediated vasoconstriction accounted for approximately three-fourths of the increase in MAP produced by AVP. No significant autoregulatory component was identified for the increases in TPR and MAP produced by ANG II or NE. We conclude that systemic vascular autoregulation is a powerful physiological property that contributes to the hemodynamic response to pressor doses of AVP. PMID- 2592566 TI - Regulation of active sodium and potassium transport in the distal colon of the rat. Role of the aldosterone and glucocorticoid receptors. AB - To determine whether mineralocorticosteroids and glucocorticosteroids have specific effects on colonic electrolyte transport, we compared the effect of aldosterone and RU 28362, a glucocorticoid receptor-specific agonist that does not bind to the aldosterone receptor, on unidirectional Na, Cl, and K fluxes across isolated mucosa of the rat distal colon. Continuous infusion of aldosterone for 7 d produced changes in four specific transport processes: induction of both active electrogenic, amiloride-sensitive sodium absorption and active electrogenic potassium secretion, enhancement of active electroneutral potassium absorption, and inhibition of electroneutral Na-Cl absorption, the predominant transport process in this epithelium. In contrast, continuous infusion of RU 28362 for 1-11 d produced a sustained increase in electroneutral Na-Cl absorption. This glucocorticoid receptor-specific agonist did not induce electrogenic sodium absorption nor affect either potassium absorption or secretion. These studies demonstrate that aldosterone (i.e., mineralocorticoid) and glucocorticoid receptors modulate separate and specific changes in active sodium and potassium transport. These results suggest that other glucocorticoids (e.g., dexamethasone, methylprednisolone) are not glucocorticoid receptor specific and that their effects on electrogenic sodium absorption and potassium transport most likely represent the binding of these agonists to the aldosterone receptor. PMID- 2592567 TI - Identification of a satellite fatty acid ethyl ester synthase from human myocardium as a glutathione S-transferase. AB - Nonoxidative alcohol metabolism catalyzed by fatty acid ethyl ester (FAEE) synthases may contribute to extrahepatic injury resulting from alcohol abuse. Unlike rabbit myocardial FAEE synthase, that from human heart has a satellite minor synthase (I) eluting from DEAE cellulose at a conductivity of 5 mS. Synthase I was purified 1,118-fold to homogeneity by sequential gel permeation, hydrophobic interaction, and Superose-12 fast-protein liquid chromatographies. SDS-PAGE showed a single polypeptide with a molecular mass of 26 kD and gel permeation chromatography indicated a molecular mass of 52 kD for the active enzyme. Homogeneous synthase I catalyzed ethyl ester synthesis at highest rates with unsaturated octadecanoic fatty acid substrates. The amino acid composition of synthase I was highly homologous to that of human myocardial major synthase, recently identified as an acidic glutathione (GSH) S-transferase. Antibody raised against homogeneous human heart major synthase cross-reacted with the 26-kD synthase I. FAEE synthase co-chromatographed with GSH S-transferase on DEAE cellulose, Sephadex G-100 and S-hexylglutathione agarose, and also displayed GSH S-transferase activity in catalyzing the conjugation of GSH with nitrobenzene containing carcinogens. Thus, human myocardium contains a satellite peak of FAEE synthase activity and it is a neutral GSH S-transferase. PMID- 2592568 TI - Glomerular hemodynamics in established glycerol-induced acute renal failure in the rat. AB - The glomerular dynamic correlates of failed filtration were studied in volume replete rats with established glycerol-induced acute renal failure (ARF). Over one-half of all nephrons formed virtually no filtrate, while the single nephron glomerular filtration rate (SNGFR) of fluid-filled nephrons, measured at the glomerulotubular junction to preclude the possibility of covert tubular leakage, averaged one-sixth of control (P less than 0.001). Even that low mean value was elevated by a few nephrons with a near normal SNGFR. Renal failure thus reflected both total filtration failure in the majority of nephrons and massively reduced filtration in most of the remainder. Glomerular capillary pressure (Pg) averaged some 14 mmHg below control (P less than 0.001), whereas the arterial colloid osmotic and Bowman's space pressures were not significantly altered. Renocortical and whole kidney blood flow were also unchanged. Marked internephron functional heterogeneity precluded estimates of the ultrafiltration coefficient. However, the fall in SNGFR correlated well with the markedly depressed Pg and afferent net filtration pressure (delta PnetA, P less than 0.001), which in turn were caused by increased preglomerular resistance and a reciprocal fall in efferent arteriolar resistance. This complex change in intrarenal resistances was largely, if not entirely, responsible for failed filtration in this ARF model. PMID- 2592569 TI - Isolation of an acidic protein from cholesterol gallstones, which inhibits the precipitation of calcium carbonate in vitro. AB - In seeking to identify nucleating/antinucleating proteins involved in the pathogenesis of cholesterol gallstones, a major acidic protein was isolated from each of 13 samples of cholesterol gallstones. After the stones were extracted with methyl t-butyl ether to remove cholesterol, and methanol to remove bile salts and other lipids, they were demineralized with EDTA. The extracts were desalted with Sephadex-G25, and the proteins separated by PAGE. A protein was isolated, of molecular weight below 10 kD, which included firmly-bound diazo positive yellow pigments and contained 24% acidic, but only 7% basic amino acid residues. The presence of N-acetyl glucosamine suggested that this was a glycoprotein. This protein at concentrations as low as 2 micrograms/ml, but neither human serum albumin nor its complex with bilirubin, inhibited calcium carbonate precipitation from a supersaturated solution in vitro. This protein could be precipitated from 0.15 M NaCl solution by the addition of 0.5 M calcium chloride. Considering that cholesterol gallstones contain calcium and pigment at their centers, and that small acidic proteins are important regulators in other biomineralization systems, this protein seems likely to play a role in the pathogenesis of cholesterol gallstones. PMID- 2592570 TI - Serum levels of interleukin 6, a potent myeloma cell growth factor, as a reflect of disease severity in plasma cell dyscrasias. AB - Using a specific and very sensitive (1 pg = 1 U) bioassay, we investigated the presence of IL-6, a potent myeloma cell growth factor, in the sera of 131 subjects with plasma cell dyscrasias. 22 had monoclonal gammopathy of undetermined significance (MGUS), 13 had smoldering myeloma (SMM), 85 had overt multiple myeloma (MM), and 11 had plasma cell leukemia (PCL). Significant serum IL-6 levels were detected in only 3% of the MGUS/SMM group, but in 35% of the overt MM group and 100% of the PCL group. During overt MM, IL-6 was detected in 37% of the patients at diagnosis, 13% of those with stable MM, and 60% of those with fulminating disease. These data demonstrate that serum levels of IL-6, a potent myeloma cell growth factor in vitro, correlate with disease severity in plasma cell dyscrasias. Serial studies performed in 3 patients and correlative studies with labeling index in vivo in 25 patients have confirmed this concept. Taken together, this suggests that this cytokine is probably involved in vivo during the progressive phase of MM. Thus, anti-IL-6 or anti-IL-6 receptor antibodies could be useful as therapeutic agents at this stage of the disease. PMID- 2592572 TI - The effects of pre-tapping on the miniscrew-bone interface in the midface. AB - The effects of pre-tapping on the AO miniscrew-midface bone interface were investigated in 140 methacrylate-fixed human cadaver specimens. An adequate contact was found in all 40 self-tapped and in 68 out of 100 pre-tapped samples. Since inadequate contact was found in the remaining 32 specimens from the pre tapped group, it was concluded that the pre-tapping was responsible for the inadequate bone screw interface. PMID- 2592571 TI - Monocyte-chemotactic activity of defensins from human neutrophils. AB - We investigated the monocyte-chemotactic activity of fractionated extracts of human neutrophil granules. Monocyte-chemotactic activity was found predominantly in the defensin-containing fraction of the neutrophil granules. Purified preparations of each of the three human defensins (HNP-1, HNP-2, HNP-3) were then tested. HNP-1 demonstrated significant chemotactic activity for monocytes: Peak activity was seen at HNP-1 concentrations of 5 X 10(-9) M and was 49 +/- 20% (mean +/- SE, n = 9) of that elicited by 10(-8) M FMLP. HNP-2 (peak activity at 5 X 10(-9) M) was somewhat less active, yielding 19 +/- 10% (n = 11). HNP-3 failed to demonstrate chemotactic activity. Checkerboard analysis of monocyte response to HNP-1 and HNP-2 confirmed that their activity was chemotactic rather than chemokinetic. Neutrophils demonstrated a low level of response to defensins but this reaction was primarily chemokinetic. Defensins may play a role in the recruitment of monocytes by neutrophils into inflammatory sites. PMID- 2592573 TI - Fibrous dysplasia and cherubism as an hereditary familial disease. Follow-up of four generations. AB - Five cases of dysplasia of the jaws in one family which has been under our observation since 1970 are reported. The disease appeared as a mixed display of jaw lesions, in some members as fibrous dysplasia and in others as cherubism. We were able to trace the disorder through an unbroken line of four generations, and thus to demonstrate autosomal dominant inheritance. Cytogenetic analysis performed on three members of this family revealed a significantly increased rate of chromosomal breakage. PMID- 2592574 TI - Cherubism. Findings in three cases in the same family. AB - Cherubism is a benign hereditary giant-cell lesion of the mandibular and maxillary spongiosa which appears during childhood between the age of 2 and 5 years and progresses until puberty when it spontaneously regresses. It appears as a bilateral, painless swelling. It normally requires no treatment. Three children in the same Algerian family who suffered from this disease were brought to our department. Radiographic examinations were carried out, giving good definition of the lesions. The 3 patients were finally operated on, as operative treatment was, effectively, necessary. PMID- 2592576 TI - Mandibular lesions in patients with adenomatosis coli. AB - Adenomatosis coli is a very interesting disease accompanied by a number of associated stigmata in the mandible. If left ignored, colonic lesions in patients with this disease proceed almost entirely to malignancy. Hence, detection of the stigmata is very important. The panoramic radiographs of 26 patients diagnosed as adenomatosis coli at the 2nd Department of Surgery, Hamamatsu University School of Medicine from 1978 to 1988 were compared with those of 264 controls. Osteomatous lesions were present in 62% of the patients with adenomatosis coli and 14% of the controls. Pantomographic comparison of the numbers and areas of the osteomatous lesions between the adenomatosis coli and control groups indicated that specific pathognomonic symptoms were demonstrated in panoramic radiographs of approximately 42% of the patients with adenomatosis coli. PMID- 2592575 TI - Widespread radiopacity of jaw bones in familial adenomatosis coli. AB - Abnormalities of jaw bones and teeth were evaluated in 37 patients with familial adenomatosis coli (FAC) by means of orthopantomography. Osteomatous radiopaque lesions were evident in 75.7 percent of FAC patients (focal type: 62.2% and wide spread type: 13.5%), odontomes in 29.7% peripheral osteomas in 13.5%, unerupted teeth in 16.2% and supernumerary unerupted teeth in 16.2%. Five of the 37 FAC patients had an unusual widespread type of radiopacity with other abnormalities. Combined abnormalities were most frequent in patients with this type in comparison with patients with the focal type. Osteomas and peripheral osteomas were revealed in this type with statistical significance. Biopsy performed in one patient revealed an osteoma. These results suggest that the multiple abnormalities seen in oral X-ray examination may predict the occult existence of familial adenomatosis coli and these widespread radiopaque lesions probably represent the most extensive manifestation of FAC. PMID- 2592577 TI - Single stage repair of the median cleft lip deformity in holoprosencephaly. AB - A single stage repair of the median cleft lip in holoprosencephaly is presented. The use of a superiorly-based pedicle from the nasal lobule/columellar remnant for columellar creation and a free skin graft from excess horizontal lip tissue for philtral reconstruction, in addition to medial rotation of the lateral lip segments, permits complete repair in one procedure. Such an approach offers the advantage of a reduction in number of procedures and anaesthetic exposure in the severely medically compromised holoprosencephalic patient. PMID- 2592578 TI - Ic antiarrhythmic drugs. PMID- 2592579 TI - FDA advisory committees and the new drug approval process. AB - To determine the impact of FDA advisory committee review on the approval time of new drug applications (NDAs) approved during the five-year period 1983 through 1987, we compared NDA phase lengths of reviewed new chemical entities (NCEs) with those that were not reviewed and examined the elapsed time from final committee recommendation for approval to NDA approval. Of the 95 drugs approved during the study period that met the Center for the Study of Drug Development's definition of an NCE, 40 (42%) were submitted for review--mean NDA phase length was 36.9 months versus 32.4 months for unreviewed drugs. Reviewed drugs in the neuropharmacologic division had a longer NDA phase, while those in the metabolic/endocrine and oncology/radiopharmaceutical divisions had shorter NDA phases, than unreviewed drugs in those divisions. For NCEs grouped by therapeutic rating, reviewed drugs in each category had longer NDA phases than unreviewed drugs; the difference was largest for 1-B rated drugs. The elapsed time from committee recommendation for approval to NDA approval as a percent of the total NDA phase was greatest for drugs submitted by the metabolic/endocrine division (83.0% of NDA phase) and for drugs rated 1-A (63.2%). Results indicate that advisory committee review is associated with a small overall delay in NDA approval when compared with the regulatory fate of drugs not submitted for review. PMID- 2592580 TI - Comparative evaluation of the effects of labetalol, verapamil and diltiazem on antipyrine and indocyanine green clearances. AB - The effects of labetalol, diltiazem and verapamil on antipyrine and indocyanine green clearance were evaluated in a placebo-controlled, repeated measures evaluation. Twelve healthy subjects received either labetalol (200 mg every 12 hours), diltiazem (90 mg. every 8 hours), verapamil (80 mg every 8 hours), or placebo (every 12 hours) for 4 days. On the morning of Day 3 immediately following their dose, the subjects assumed the supine position for 90 minutes, after which time a 0.5 mg/kg dose of indocyanine green was administered. Blood samples were obtained serially over a 20 minutes period for indocyanine green plasma concentration determinations by HPLC. Ten minutes later, subjects ingested a 1.2 Gm. dose of antipyrine and blood samples were obtained over a 48 hour period for antipyrine plasma concentration determinations by HPLC. A 2 week washout period separated treatment sequences. Mean (SD) antipyrine clearance (L/hr/kg) following diltiazem [0.028 (0.010)] and verapamil [0.030 (0.012)] treatment was significantly lower than that observed following placebo [0.039 (0.012)]. Antipyrine clearance following labetalol administration [0.033 (0.010)] was not significantly different from that observed following placebo, diltiazem or verapamil administration. No effects of these drugs on indocyanine green clearance could be detected. PMID- 2592581 TI - Pharmacokinetics and dynamics of heparin in patients with proximal vein thrombosis. PMID- 2592582 TI - Pharmacokinetics and efficacy of digoxin specific Fab fragments in a child following massive digoxin overdose. AB - The use of digoxin-specific Fab fragments (d-Fab) to treat life-threatening digitalis intoxication has been widely substantiated in adults. This reports a case of a 2-year-old girl who ingested 90-92, 0.25 mg tablets of digoxin and within four hours, developed vomiting, lethargy, tachycardia and AV block (Mobitz type I and II). These symptoms were associated with total and free serum digoxin concentrations of 17.1 and 12.4 ng/ml, respectively. Following GI decontamination, a total dFab dose of 1280 mg (32 vials) was given with resolution of electrocardiographic abnormalities within 40 minutes and a concomitant reduction in the free serum digoxin concentration to 0.11 ng/ml. Repeated blood sampling over 19 days revealed an apparent elimination half-life (t1/2) of 134.9 and 129.9 hr for total and free digoxin, respectively. The long t1/2 for digoxin corresponded to a low apparent renal clearance of total digoxin which ranged from 0.56 to 0.82 ml/minute over four separate collection intervals. The free serum digoxin concentration never exceeded 3% of the total concentration and the patient did not develop a recurrence of toxic symptoms or any adverse effects (e.g. fever) attributable to dFab. Administration of an equimolar dFab dose to children following acute, massive digoxin intoxication represents safe, effective treatment which produces a prompt, sustained reversal of toxic effects. Digoxin specific Fab fragments should be promptly administered to any infant or child with significant, life-threatening symptoms following acute digoxin intoxication. PMID- 2592583 TI - Chronopharmacological study of nitrendipine in healthy subjects. AB - Nitrendipine 20 mg or placebo was given orally to eight healthy subjects in a cross-over design separated by 1 or 2 weeks. Drug was given at 9:00 AM (morning dosage) or at 9:00 PM (evening dosage). Systolic and diastolic blood pressure (SBP, DBP) were measured just before and 1, 2, 3, 4, 5, 7, 9, 12 and 24 hrs after treatment. Plasma nitrendipine concentrations were determined at 0.5, 1, 2, 3, 4, 5, 7, 9, 12 and 24 hrs and plasma catecholamines were measured at 2 and 5 hrs following drug administration. SBP did not decrease significantly after nitrendipine compared to after placebo at 9:00 AM or at 9:00 PM. DBP decreased significantly at 2, 3, 4 and 5 hrs after nitrendipine at 9:00 AM, but only at 4 hours after the 9:00 PM dose. Mean plasma nitrendipine concentrations during the absorption phase were lower after the evening dosage compared to the morning interval. Maximum plasma concentration (Cmax) was significantly lower and time to maximum concentration (tmax) tended to be longer after the evening dosage. Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) and half life of the terminal elimination phase (t1/2 beta) of the morning and evening dosages did not differ. A significant correlation was observed between plasma nitrendipine concentrations and changes in DBP during the drug treatment. Plasma noradrenaline concentrations were significantly higher 5 hours after nitrendipine compared to after placebo at 9:00 AM, but not at 9:00 PM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592584 TI - Urinary excretion of prednisolone following intravenous administration in humans. AB - The urinary excretion of prednisolone was studied in eight normal human volunteers (two women and six men) following intravenous (16, 32, 48 and 64 mg) doses. Urine prednisolone concentrations were determined by a high performance thin layer chromatographic method (HPTLC). The overall mean prednisolone elimination half life in urine following all the intravenous doses as determined by the rate and sigma minus plots was 1.13 +/- 0.25 hour. This was independent of dose and shorter than that found in plasma (4.10 +/- 1.00 s.d. hour). The overall mean percentage of dose excreted unchanged in urine was 16.7 +/- 5.8% following all intravenous and oral doses respectively. About 80% of this amount was excreted within the first 4 hours of the intravenous administration. Renal clearance of prednisolone decreased with time by the first order kinetic (r = 0.790) and its overall value following all IV doses was 0.0183 +/- 0.0103 (s.d.) l/h/kg. The metabolic clearance remained constant with increasing doses from 16 to 64 mg (0.0883 +/- 0.0306 s.d. l/h/kg). From this study it was concluded that a definitive account of the renal elimination of prednisolone and its possible metabolites warrant further investigation. The fraction of the dose excreted unchanged was relatively small and variable suggesting that prednisolone elimination occurs mainly by metabolism. PMID- 2592585 TI - Effect of nifedipine on urinary concentrating ability: a placebo controlled study. AB - A placebo-controlled, randomized, crossover study was conducted to assess a possible effect of a dihydropyridine Ca-entry blocker, nifedipine, on urinary concentration ability in nine healthy men under a water-deprivated condition. Placebo and nifedipine (20 mg) were orally administered on two separate occasions, at least one week apart, after the urinary osmolarity was stabilized. Urinary osmolarity, osmolar clearance, negative free water clearance, urine volume, urinary solutes (Na, K and urea), creatinine clearance and plasma vasopressin (AVP) were measured during the postdose 3-hour period and compared with those during the respective predose (baseline) period. Urinary osmolarity decreased by nifedipine from 1047.2 +/- 34.4 to 873.0 +/- 38.3 mOsm/kg (mean +/- SEM) at 2 hours postdose (P less than 0.05). Mean % decrease in urinary osmolarity at 1 to 3 hours after nifedipine was significantly (P less than 0.01) greater than after placebo. Urine volume significantly (P less than 0.01) increased from the baseline of 0.49 +/- 0.06 to 1.1 +/- 0.15 ml/min at 2 hours after nifedipine. Relationship between osmolar clearance and negative free water clearance relative to glomerular filtration rate observed during the postnifedipine phase was significantly (P less than 0.01) shifted downward compared with that derived from the pooled data unrelated to nifedipine dosing. No significant drug effect was detected on plasma AVP. Both placebo and nifedipine dosed during the continued water deprivation and stabilized urinary osmolarity condition caused an increase in the urinary excretions of solutes. The results indicate that nifedipine inhibits urinary concentration. This does not appear to be due to the inhibition of AVP secretion from the hypophysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592586 TI - Ciprofloxacin pharmacokinetics after a standard or high-fat/high-calcium breakfast. PMID- 2592588 TI - "Dingelling". PMID- 2592587 TI - The effect of food on the bioavailability of velnacrine (HP 029) in healthy elderly men: a potential Alzheimer agent. AB - Velnacrine (HP 029; 1,2,3,4-tetrahydro-9-aminoacridin-1-ol-maleate) is an investigational drug being studied in patients with Alzheimer's disease. In this open, randomized, crossover study, 24 healthy, elderly men were given 100 mg of velnacrine on two different study days to assess the influence of food on the bioavailability of velnacrine. On the first day, subjects received drug either after an overnight fast or 15 minutes after completing a standard breakfast. Seven days later, the treatments were crossed over. Blood and urine samples were collected at specific times and various intervals, respectively, from all subjects before and after drug administration for up to 24 hours. Plasma and urine concentrations of velnacrine were determined by an HPLC method. Administration of velnacrine with food resulted in slightly lower peak plasma levels of unconjugated velnacrine, (175 vs 213 ng/ml) and delayed times-to-peak plasma levels, (2.5 vs 1.5 h) without affecting the AUCs and the t 1/2 of the drug. The amount of unconjugated velnacrine excreted in urine was slightly higher when the drug was taken with food (19 vs 17 mg), but renal clearance was not altered. These results indicate that food delayed the rate but not the extent of velnacrine absorption. The minor differences in Cmax and tmax may not be clinically meaningful. Therefore, velnacrine can be administered with or without food. PMID- 2592589 TI - Dietary restriction, tyramine, and the use of monoamine oxidase inhibitors. AB - The aim of this study is to provide clearer guidelines for rational, safe, and practical dietary restriction for use with monoamine oxidase inhibitors. Tyramine levels were assayed in over 100 of the controversial foods that have been associated with hypertensive reactions or reported to contain high levels of tyramine. Only a very limited number of foods appear to require absolute restriction. These include all aged cheeses, concentrated yeast extracts (e.g., Marmite), sauerkraut, and broad bean pods. Alcoholic beverages, including Chianti wine consumed in moderation, appear to be safe. Some aged meats contain relatively high levels of tyramine and require closer investigation. PMID- 2592590 TI - Characterizing anticholinergic abuse in community mental health. AB - To identify factors associated with anticholinergic abuse in patients taking antipsychotics and anticholinergics and to document the extent of extrapyramidal side effects in anticholinergic abusers, 21 anticholinergic abusers were matched with 21 controls without a history of anticholinergic abuse for diagnosis and antipsychotic dose. Data were collected prospectively, and extrapyramidal side effects and abnormal involuntary movements were evaluated using the Modified Simpson Angus Scale and the Abnormal Involuntary Movement Scale. The abuse group reported significantly more subjective effects from anticholinergic agents than did those in the control group (mean +/- SD = 10.5 +/- 5.4 vs. 6.5 +/- 3.7, p less than 0.05). The abuse group was significantly more likely to report feeling a buzz (p less than 0.05) and difficulty learning (p less than 0.05) when taking anticholinergic medications. Abusers reported abusing significantly more drugs in the past (2.7 +/- 2.1 vs. 0.8 +/- 0.9, p less than 0.01) and had taken antipsychotics (12.7 +/- 6.3 vs. 8.7 +/- 5.4 years, p less than 0.05) and anticholinergics (10.9 +/- 3.1 vs. 6.1 +/- 4.6 years, p less than 0.01) significantly longer than controls had. Patients in the control group spent significantly more years working full-time than did abusers (6.2 +/- 7.3 vs. 0.7 +/- 1.4, p less than 0.01). There was a nonsignificant trend for abusers with a longer duration of antipsychotic use to have higher Abnormal Involuntary Movement Scale scores (r = 0.40, p less than 0.10). Although these drugs are potentially abusable, the term "anticholinergic abuse" should be reevaluated in light of accumulating evidence that many patients taking these drugs report improved functioning, with improvement in negative symptoms and minimal or no adverse anticholinergic effects. PMID- 2592591 TI - Low serum iron levels and tricyclic antidepressant-induced jitteriness. PMID- 2592592 TI - Reversal of self-abusive behavior with naltrexone. PMID- 2592593 TI - Trazodone for the treatment of anxiety symptoms in substance abusers. PMID- 2592594 TI - Diurnal variation in methylphenidate stimulant response in major depression. PMID- 2592595 TI - Amphetamine, but not methylphenidate, predicts antidepressant response. PMID- 2592596 TI - Quantitative analysis of cone photoreceptor-horizontal cell connectivity patterns in the retina of a cyprinid fish: electron microscopy of functionally identified and HRP-labelled horizontal cells. AB - Horizontal cells generating photopic luminosity and biphasic/chromaticity-type S potentials were identified and intracellularly labelled with horseradish peroxidase in the retina of the roach. The synaptic connectivity patterns of the horizontal cell dendrites within pedicles of different spectral types of cone were then quantitatively studied by electron microscopy. Luminosity-type responses were generated by H1-like horizontal cells contacting similar numbers of red- and green-sensitive cones and very few blue-sensitive cones. Most dendritic contacts were lateral to synaptic ribbons. Central contacts with ribbons were made almost exclusively within red-sensitive cone pedicles. Biphasic/chromaticity-type S-potentials were generated by H2-like horizontal cells. The dendrites of the latter contacted green- and blue-sensitive cones, both at central and lateral sites at synaptic ribbons. An attempt was made to correlate cone ribbon connectivity patterns and spectral characteristics of the horizontal cells according to several hypotheses, some proposed in earlier studies. PMID- 2592597 TI - Afferent connections of the valvula cerebelli in two teleosts, the common goldfish and the green sunfish. AB - The afferent connections of the valvula cerebelli were examined in one cypriniform teleost (Carassius auratus) and one perciform teleost (Lepomis cyanellus) with the use of horseradish peroxidase as a retrograde tracer. Both species have ipsilateral input to the valvula from the central pretectal and dorsal accessory optic nuclei, the dorsal and ventral tegmental nuclei, the lateral nucleus of the valvula, the perilemniscal nucleus, and nucleus isthmi and contralateral input from the inferior olivary nucleus. In addition, Carassius has ipsilateral valvulopetal projections from the eminentia granularis, the prae eminential nucleus, and the isthmic primary sensory trigeminal nucleus, whereas Lepomis has bilateral (stronger ipsilaterally) valvulopetal projections from the nucleus of the locus coeruleus and the rostral corpus cerebelli. The topographical order of the cerebellopetal projections of the lateral nucleus of the valvula and inferior olive is also described, as are differential inputs to various subdivisions of the cerebellum in the two species. Information on valvulopetal projections in teleosts has thus far been limited to electroreceptive mormyrids. The present study shows that many valvular inputs related to electroreception in mormyrids have no homologue in Carassius and Lepomis. Finally, the present study indicates that the rostral part of the corpus cerebelli, but not the valvula cerebelli, in teleosts is the homologue of the anterior lobe of the corpus cerebelli in cartilaginous fishes. Thus, the valvula cerebelli is a shared derived feature (synapomorphy) of all ray-finned fishes. PMID- 2592598 TI - Cells of origin of spinothalamic tract projections to the medial and lateral thalamus in the cat. AB - The double fluorescent retrograde labeling method was used to examine the distribution of spinothalamic tract (STT) cells that project to the medial and lateral thalamus in the cat. Injections of one fluorescent tracer (Fast Blue or Diamidino Yellow) were made throughout the lateral thalamus and injections of the other tracer were made in the medial thalamus at sites extrapolated from recording track coordinates. Survival times were successively extended (up to 5 weeks) in order to maximize labeling in both the cervical and lumbosacral spinal cord. On average, over 2,000 labeled contralateral STT cells were counted in serial sections from segments C5-7 and L5-S2. Numerical variability of the order of a factor of two was attributable to inherent differences between individual animals. The total number of cells labeled with fluorescent tracers was comparable to the number labeled with horseradish peroxidase in control cases, although there were significant differences between the laminar distributions of labeling produced by the two methods. Injections made anterior to the thalamus to control for labeling due to leakage or passing fibers did not produce substantial spinal labeling. The laminar distribution of fluorescent dye-labeled STT cells was consistent; about half (47%) were located in lamina I, 8% were in lamina V, 5% in lamina VI, 20% in lamina VII, and 20% in lamina VIII. The proportions of STT cells in laminae I and V were higher in cervical segments (57% and 12%, respectively) than in lumbosacral segments (38% and 6%). The dominant contribution of lamina I cells to the STT thus revealed by the fluorescent tracers is striking. The proportions of STT cells labeled from the medial and the lateral thalamus varied with segmental and laminar location and with injection placement. The majority (62%) of STT cells in most cases projected only to the medial thalamus, 25% projected only to the lateral thalamus, and 13% projected to both. The STT cell populations in laminae I, VII, and VIII each displayed this common projection pattern. In contrast, cells in laminae V and VI projected predominantly to the lateral thalamus. Twice as many STT cells in lamina I (19%) projected to both the medial and the lateral thalamus as from other laminae. A greater proportion of laminae V-VIII STT cells in segments L5-6 projected to the lateral thalamus, and in S1-2, more projected to the medial thalamus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2592599 TI - Morphometric modifications associated with early sensory experience in the rat olfactory bulb: I. Volumetric study of the bulbar layers. AB - Current models of sensory coding in the olfactory bulb are based on the notion of topographical specificity in the processing of stimuli. Part of this hypothesis comes from studies of patterns of radiolabelled 2-deoxyglucose uptake, and local morphometric variations of the mitral cell size observed following prolonged exposure to an odor. The present study explored the possibility that exposing young rats to a long-term stimulation with an odor would induce spatially distributed volumetric variations of the bulbar layers. Three groups of 5 rats have been studied: (1) stimulated with ethyl acetoacetate from birth to 1 month of age, (2) unilaterally deprived following early cauterization of one nostril, and (3) normal animals of same age. Fourteen frontal histological sections uniformly distributed along the rostrocaudal axis of the olfactory bulb were used for this study. Areas of the bulbar layers were measured with the aid of an image analyser and the volume of the corresponding layers deduced by computation. Following complete sensory deprivation, the volume of all bulbar layers, except the periventricular core, was homogeneously reduced along the rostrocaudal axis of the olfactory bulb. Following long-term stimulation with ethyl acetoacetate, volume reduction was significantly higher in anterior and middle regions than in the posterior part of the olfactory bulb. It is assumed that neuronal pathways activated by ethyl acetoacetate stimulation are mainly located in the posterior part of the olfactory bulb. Functional interpretations of these results are discussed with respect to the spatial dimension in olfactory coding. PMID- 2592600 TI - Morphometric modifications associated with early sensory experience in the rat olfactory bulb: II. Stereological study of the population of olfactory glomeruli. AB - The present study explores the local variations of size and number of olfactory glomeruli induced by the exposure of young rats to long-term stimulation with a single odor. Three groups of 5 rats were used that were either: (1) stimulated with ethyl acetoacetate from birth to 1 month of age, (2) unilaterally deprived following early occlusion of one nare, or (3) normal animals of the same age. Areas and coordinates of all glomerular profiles were measured in 14 coronal sections uniformly distributed along the rostrocaudal axis of the olfactory bulb. A distribution-free stereological method was applied to compute the size and number of glomeruli either along the bulbar rostrocaudal extent or in the bulbar coronal plane. Following complete sensory deprivation or long-term stimulation with ethyl acetoacetate, the mean diameter of glomeruli was significantly reduced everywhere, except in the ventrolateral and ventromedial regions of the posterior olfactory bulb in rats reared with a single odor. In both of these areas, the number of glomeruli was either significantly increased following long duration exposure or significantly reduced following unilateral deprivation. Thus these results show that selective modifications of the olfactory environment during postnatal maturation induce morphometric variations in specific areas of the glomerular layer. These data are discussed with respect to the concept of the topographical coding of odor quality at the level of the glomeruli and plasticity of the olfactory system during postnatal development. PMID- 2592601 TI - Anatomical evidence of the projection of pontine omnipause neurons to midbrain regions controlling vertical eye movements. AB - Both anatomical and physiological studies have shown that pause neurons (PNs) in the medial pontine reticular formation project to two groups of burst neurons (BNs) involved in the genesis of horizontal saccadic eye movements: The excitatory burst neurons (EBNs), which lie rostral to the abducens nucleus, and the inhibitory burst neurons (IBNs), which lie caudal to the abducens. This study is concerned with the projection from PNs to a group of vertical BNs in the nucleus of the H field of Forel (H FF) in the caudomedial subthalamus. Three anatomical methods were used to demonstrate this connection. First, intra-axonal horseradish peroxidase (HRP) injection into physiologically identified PN axons demonstrated axonal branching and axonal terminations in and around the H FF. Second, micro-injection of the tracer Phaseolus vulgaris leucoagglutinin (PHA-L) into the pontine PN region labelled terminal axons and boutons in the nucleus of the H FF. Third, extracellular pressure injection of HRP into H FF yielded retrogradely labelled pontine PN neurons. These anatomical results confirmed the termination of PNs in areas controlling rapid vertical eye movements as physiologically demonstrated by Nakao et al.: Exp. Brain Res. 70:632-636, '88). This work points to the major role of pontine PNs in the synchronization of BN activity in rapid eye movements in all directions. PMID- 2592602 TI - Organization of the projections from the trigeminal brainstem complex to the superior colliculus in the rat and hamster: anterograde tracing with Phaseolus vulgaris leucoagglutinin and intra-axonal injection. AB - Anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and intra axonal recording and injection techniques were employed to describe the projection from the trigeminal (V) brainstem complex to the deep laminae of the superior colliculus (SC) in the hamster and the rat. The organization of these projections was the same in the two species. Deposits of PHA-L into V nucleus principalis (PrV) produced labelled axons and boutonlike swellings in the lower stratum griseum intermediale (SGI) and upper stratum album intermedium (SAI) in the SC bilaterally. Plots of boutonlike swellings indicated that the terminals of this projection were arrayed in clusters. Nucleus principalis also projected to the stratum griseum profundum (SGP) and stratum album profundum (SAP). This deeper projection did not terminate in clusters and it was most prominent in the lateral SC. The ipsilateral PrV-SC projection appeared to arise mainly from axons that recrossed the midline at the level of the SC commissure. Reconstruction of individual PHA-L labelled fibers demonstrated that single axons gave rise to terminals on both sides of the midline. Deposits of PHA-L into V subnucleus interpolaris (SpI) yielded results that were identical to those obtained with PrV injections with one exception: none of these deposits produced any labelled terminals in the ipsilateral SC. Deposits of PHA-L into V subnucleus caudalis (SpC) produced only sparse labelling in SC. Most labelled swellings were located in the SGP and SAP and they were visible only in the SC contralateral to the PHA L injection site. Single axons arising from cells in SpI were recorded and injected with horseradish peroxidase (HRP) in the hamster's SC. These fibers all responded to stimulation of multiple mystacial vibrissae and gave rise to 2-5 clusters of bouton-like swellings in the lower SGI and upper SAI. PMID- 2592603 TI - Distribution of corticotropin-releasing factor in the cerebellum and precerebellar nuclei of the cat. AB - The present study analyzes the distribution of corticotropin-releasing factor immunoreactive (CRF-IR) fibers and neuronal cell bodies within the cerebellum and brainstem, respectively, of the cat. Within the cerebellum, CRF is present in climbing fibers, mossy fibers, and a population of varicose fibers which traverses the lower molecular layer. CRF-IR fibers are present throughout all lobules of the cat cerebellar cortex, though the density and immunostaining intensity of each fiber system vary. Bands of intensely immunoreactive climbing fibers are prominent within the vermis, intermediate cortex, and crus II. Bands of intensely immunoreactive mossy fiber terminals accompany the climbing fiber bands within the vermis. Collaterals of climbing and mossy fibers contribute to a beaded fiber plexus localized to the Purkinje cell layer. Varicose fibers containing CRF immunoreactivity are present in all deep cerebellar nuclei. CRF-IR neuronal cell bodies are prominent within several brainstem nuclei known to project to the cerebellum: all divisions of the inferior olivary complex, the lateral reticular nucleus, paramedian reticular nucleus, gigantocellular reticular nucleus, raphe nuclei, perihypoglossal complex, medial and inferior vestibular nuclei and cell groups f and x, locus ceruleus, and nucleus subceruleus. This study confirms and extends a previous study of CRF distribution within cerebellar afferent systems of the cat (Cummings et al.: J. Neurosci. 8:543-554, '88) and compares this distribution with previous descriptions in other species. The ubiquitous distribution of CRF throughout the cat cerebellum suggests a primary role for this peptide in signal transduction. PMID- 2592604 TI - Cells in laminae III and IV of rat spinal dorsal horn receive monosynaptic primary afferent input in lamina II. AB - In order to determine how information conveyed by fine primary afferent fibres might reach the deeper laminae of the spinal dorsal horn, 5 Golgi-stained neurones with somata in lamina III or IV and dendrites that entered lamina II were examined by electron microscopy. Three of the cells were from animals in which 2 or 3 dorsal roots had been cut 26 or 30 hours previously. These cells received numerous synapses in lamina II, and between 13 and 16% of these (24-31% of asymmetric synapses) were from degenerating axons. Synapses with degenerating axons were found throughout the depth of lamina II, including the dorsal part, which receives primary afferent input from myelinated nociceptors and from unmyelinated axons. In addition, all 3 cells were postsynaptic to degenerating axons within lamina III. The 2 cells from unoperated animals also received many synapses within lamina II and at some of these the presynaptic axon was the central terminal of a glomerulus. Only one example of a dendrodendritic synapse involving a stained dendrite was seen. Cells of laminae III and IV may therefore not be a major target for presynaptic dendrites of cells in lamina II. It is concluded that one way in which information carried by primary afferents passes from the superficial dorsal horn to the deeper laminae is through monosynaptic contacts between these afferents and the dorsal dendrites of some cells whose somata are situated in laminae III and IV. If the axons of these cells generate local collaterals, this may account for some of the activation of cells whose dendrites do not enter lamina II. PMID- 2592605 TI - Auditory cortical projection from the anterior ectosylvian sulcus (Field AES) to the superior colliculus in the cat: an anatomical and electrophysiological study. AB - Sensory activity in the deep layers of the superior colliculus (SC) is strongly influenced by descending cortical inputs. Elimination (permanent or reversible) of specific regions of visual or somatosensory cortex, known to have direct access to the SC, abolishes or dramatically reduces SC responses to stimuli from those modalities. While many SC neurons are also responsive to auditory cues, the origin of auditory corticotectal connections is not clear at present and their affect on activity in the SC is unknown. Therefore, the present study was undertaken to determine the origin, organization, and functional characteristics of auditory corticotectal projections. Of the auditory cortices (AI; AII; Fields A, P, and VP), only the auditory subregion of the banks of the anterior ectosylvian sulcus (Field AES) showed a robust anatomical projection to the SC. These data were confirmed physiologically: auditory neurons in Field AES projected to the SC and auditory SC neurons responded to stimulation of the Field AES. However, neither anatomical nor physiological techniques revealed a clear topographic relationship between the Field AES and the SC but suggested instead a diffuse and extremely divergent/convergent projection. Stimulation and cryoblockade of Field AES demonstrated the excitatory nature of this corticotectal pathway, whose influence was most evident on SC responses to stimuli of reduced intensity. Given the short latency of this ear-cortex-SC circuit and its excitatory influence on unimodal as well as on multisensory auditory neurons, it seems likely that Field AES plays a significant role in facilitating SC responses to auditory stimuli. PMID- 2592606 TI - Morphology of midlumbar interneurones relaying information from group II muscle afferents in the cat spinal cord. AB - The morphology of midlumbar interneurones with peripheral input from group II muscle afferents was analysed after intracellular injection of horseradish peroxidase (HRP). Twenty-three interneurones were stained intrasomatically and five others intra-axonally. The majority (10 of 13) of interneurones located in lamina VII (intermediate zone and ventral horn interneurones) were found to project ipsilaterally. They had medium-sized somata and dendrites projecting radially over a distance of more than 1 mm. All of these neurones had axons that projected caudally within the ventral part of the lateral funiculus or in the lateral part of the ventral funiculus, although four had in addition an ascending secondary axonal branch. Numerous axon collaterals were given off from these axons, both before and after they left the grey matter. The collaterals arborized within laminae VII, VIII, and IX, where they covered the area of several motor nuclei. Intra-axonal labelling of five neurones with similar input and axon trajectories revealed several axon collaterals given off between the cell body and the terminal projection areas in L7 or S1 segments. Only three of the labelled interneurones located in lamina VII and displaying the same kind of input had axons with different destinations; their axons crossed to the opposite side of the spinal cord and ascended within the contralateral ventral funiculus. These were large neurones with extensive dendritic trees, which had fairly thick axons with initial axon collaterals that branched primarily ipsilaterally (within laminae V-VIII). Interneurones located in lamina V and in the bordering parts of laminae IV and VI (dorsal horn interneurones; n = 10) constituted a very nonhomogenous population. They projected either ipsilaterally or contralaterally and had either ascending or descending axons running in either the lateral or ventral funiculi. Generally, dorsal horn interneurones had cell bodies smaller than those of intermediate zone and ventral horn interneurones, and their dendrites extended less extensively and less uniformly around the soma. Their initial axon collaterals branched primarily in the dorsal horn, or in lamina VII, but not in or close to the motor nuclei. Our results support the conclusions of previous physiological studies that the intermediate zone and ventral horn midlumbar interneurones with group II input and that project to motor nuclei have collateral actions on other interneurones in the L4-L6 segments, and that dorsal horn interneurones do not project to motoneurones, but have as their targets other interneurones or ascending cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2592607 TI - Immunocytochemical reactivity of Xenopus laevis retinal rods and cones with several monoclonal antibodies to visual pigments. AB - Immunocytochemical reactions with several antibodies to visual pigments were used to study visual cells of the Xenopus laevis retina. Monoclonal antibodies to bovine opsin "E," 1D4, and 4B4 (reactive with the N- and C-terminus and with the loop connecting transmembrane segments 5-6, respectively) and to chicken visual pigments COS-1 and OS-2 (binding to mammalian red/green and blue cones, respectively), as well as a rabbit antifrog opsin serum 11-7, were applied to semithin and thin sections of the retina. The bound antibodies were detected with the peroxidase technique at the light microscopic level; a three-stage immunogold procedure was used for electron microscopic immunocytochemistry. The overwhelming majority of rods were labeled by monoclonal antibodies "E," 4B4, 1D4, OS-2, and serum 11-7. A small fraction (2-3%) of rods did not bind monoclonal antibodies "E" and 4B4, but this minor population of rods was strongly reactive with 1D4 and to a lesser extent with OS-2, indicating the presence of different visual pigment. These rods differ in shape from the major rod type; they are thinner, shorter, and may be comparable to the blue-sensitive ("green") rods of other amphibia. Cones were morphologically heterogeneous: double cones, large single cones, and small single cones were found, and the large single and the double cones were occasionally duplicated. Double cones and large single cones (as well as their duplicated varieties) strongly bound monoclonal antibodies COS-1 and were unlabeled by all other monoclonal antibodies, except OS-2. The small single cone was remarkably unreactive with COS-1 and "E," weakly labeled by 1D4 and 4B4, and most reactive with OS-2 and 11-7. This unique pattern of immunocytochemical reactions in the small cone type indicates the uniqueness of its visual pigment from other cone types in the Xenopus retina. The present study shows the existence of two different opsins in morphologically distinct (thick and thin) rod types and at least two cone pigments in the heterogeneous cone population. PMID- 2592608 TI - Development of the electrosensory nervous system in Eigenmannia (Gymnotiformes): I. The peripheral nervous system. AB - The nerves of the anterior lateral line system in embryonic and larval stages of the weakly electric gymnotiform fish Eigenmannia were visualized by injection of the fluorescent marker DiI into the primordium of the anterior (ALLN) and posterior (PLLN) lateral line nerves. Examination of developmental series reveals that the nerve fibers that innervate the electrosensory and mechanosensory components of the anterior lateral line system are present before the first mechanoreceptors and electroreceptors have differentiated. This suggests that nerve fibers might induce the formation of lateral line receptors. Whereas the innervation of the mechanoreceptive system is already established at an early stage, the afferent innervation of electroreceptors continues to arborize in the periphery, presumably by following pioneer axon pathways. The earliest recognizable stage of the anterior lateral line nerve ganglion (ALLNG) is evident 2 days after spawning. The ganglion shows two germinal cell masses that develop into the supraorbital-infraorbital and the hyomandibular placodes. The supraorbital-infraorbital placode forms the dorsal part of the ALLNG; the hyomandibular placode forms the ventral part of the ALLNG. Counts of ALLNG cells in embryonic, larval, and adult stages of Eigenmannia show that, at each stage examined, the number of ganglion cells is always significantly larger than the number of mechanoreceptors and electroreceptor units in the periphery. During development, the distribution of ALLNG cell diameters shifts from a unimodal distribution in juveniles to a bimodal distribution in adults, peaking at 8 microns and 18 microns. These results suggest that tuberous electroreceptive organs, which are innervated by the large ALLNG cells, may not be functional prior to day 18. Our results further suggest that the number of ALLNG cells correlates with the rate of induction of lateral line receptors in the periphery. PMID- 2592609 TI - Cholinergic innervation of the rat cerebellum: qualitative and quantitative analyses of elements immunoreactive to a monoclonal antibody against choline acetyltransferase. AB - Cholinergic innervation of the rat cerebellum was investigated immunohistochemically by using a monoclonal antibody against choline acetyltransferase. Immunoreactive structures included: 1) a subpopulation of mossy fibers and glomerular rosettes; 2) thin varicose fibers, which were closely associated with the Purkinje cell layer and also found in the molecular layer; and 3) relatively dense networks of varicose fibers distributing in the cerebellar nuclei. Quantitative analysis indicated that a great many immunoreactive rosettes were localized in lobules IXc and X, although their density in lobule X was approximately four times that in the lobule IXc. A considerable number of immunoreactive structures were also present in all other lobules. In the hemispheres they were confined to a zone immediately beneath the Purkinje cell layer, whereas in the vermis they were scattered throughout the granular layer. Most of the immunoreactive fibers found in the molecular layer coursed toward the pial surface and were distributed within the inner half of the molecular layer. In the cerebellar nuclei, portions of the medial nucleus and magnocellular portion of the lateral nucleus had moderately dense networks of immunoreactive fibers, whereas loose networks of fibers were observed in the posterior interposed nucleus. Other parts of the cerebellar nuclei contained a smaller number of varicose fibers. PMID- 2592610 TI - Amygdaloid efferents through the stria terminalis in the rat give origin to zinc containing boutons. AB - Many regions of the basal forebrain are innervated by zinc-containing axonal boutons. In the present work, the lesion/degeneration method, coupled with histochemical staining for zinc-containing boutons, was used to determine the origins and efferent pathways of these zinc-containing projections to the basal forebrain. Knife cuts of the stria terminalis or extensive electrolytic lesions of the amygdala resulted in the bleaching of the staining for zinc (Timm stain) and terminal degeneration (Fink-Heimer method) ipsilaterally in the following areas: granule cell layer of the accessory olfactory bulb, shell of nucleus accumbens, bed nucleus of the stria terminalis, striohypothalamic nucleus, retrochiasmatic area, ventromedial hypothalamic nucleus (in the cell-sparse shell), medial tuberal nucleus, terete hypothalamic nucleus, and ventral premammillary nucleus. Small lesions made with ibotenic acid in the posteromedial part of the amygdalohippocampal area caused bleaching of the stain for zinc in the accessory olfactory bulb, in the medial zone of the bed nucleus of the stria terminalis, and in the ventral premammillary nucleus. Lesions in either the ventral subiculum or the anterolateral part of the amygdalohippocampal area caused bleaching in the ventromedial hypothalamic nucleus. Lesions in the hippocampus or in the neocortex did not produce bleaching of the stain for zinc in the above-mentioned terminal fields. The present results agree with previous studies on amygdaloid efferents and suggest that neurons in the amygdalohippocampal area and, possibly, in the ventral subiculum give origin to zinc-containing boutons. PMID- 2592611 TI - Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: an anterograde tract-tracing study with Phaseolus vulgaris leucoagglutinin. AB - The purpose of the present investigation was to examine the topographical organization of efferent projections from the cytoarchitectonic divisions of the mPFC (the medial precentral, dorsal anterior cingulate and prelimbic cortices). We also sought to determine whether the efferents from different regions within the prelimbic division were organized topographically. Anterograde transport of Phaseolus vulgaris leucoagglutinin was used to examine the efferent projections from restricted injection sites within the mPFC. Major targets of the prelimbic area were found to include prefrontal, cingulate, and perirhinal cortical structures, the dorsomedial and ventral striatum, basal forebrain nuclei, basolateral amygdala, lateral hypothalamus, mediodorsal, midline and intralaminar thalamic nuclei, periaqueductal gray region, ventral midbrain tegmentum, laterodorsal tegmental nucleus, and raphe nuclei. Previously unreported projections of the prelimbic region were also observed, including efferents to the anterior olfactory nucleus, the piriform cortex, and the pedunculopontine tegmental-cuneiform region. A topographical organization governed the efferent projections from the prelimbic area, such that the position of terminal fields within target structures was determined by the rostrocaudal, dorsoventral, and mediolateral placement of the injection sites. Efferent projections from the medial precentral and dorsal anterior cingulate divisions (dorsomedial PFC) were organized in a similar topographical fashion and produced a pattern of anterograde labeling different from that seen with prelimbic injection sites. Target structures innervated primarily by the dorsomedial PFC included certain neocortical fields (the motor, somatosensory, and visual cortices), the dorsolateral striatum, superior colliculus, deep mesencephalic nucleus, and the pontine and medullary reticular formation. Previously unreported projections to the paraoculomotor central gray area and the mesencephalic trigeminal nucleus were observed following dorsomedial PFC injections. These results indicate that the efferent projections of the mPFC are topographically organized within and across the cytoarchitectonic divisions of the medial wall cortex. The significance of topographically organized and restricted projections of the rat mPFC is discussed in light of behavioral and physiological studies indicating functional heterogeneity of this region. PMID- 2592613 TI - Cell proliferation during early development of the chick embryo otic anlage: quantitative comparison of migratory and nonmigratory regions of the otic epithelium. AB - During development of the otic anlage, a certain proportion of epithelial cells migrate toward the mesenchymal compartment to form part of the acoustic vestibular ganglion. The migrating cells are observed only in the zone of the otic anlage that will make contact with the acoustic-vestibular ganglion (so called ganglion zone). In Hamburger and Hamilton's stages 13 to 16, the number of epithelial cells that migrate is relatively low, but it becomes steadily higher from stage 17 on. In the otic anlage of chick embryos, between developmental stages 9 and 21 (48 to 94 hours of incubation), mitotic index, apical or basal localization within the epithelium of dividing cells, and orientation of the mitotic spindles were analyzed. These features in the ganglion zone were compared with observations in the rest of the otic epithelium, where migratory processes do not take place. In stages 13 to 15, when few epithelial cells are migrating, the mitotic index (MI) in the ganglion zone of the otic anlage is similar to that in nonmigratory regions. In more advanced stages, however, when cell migration becomes accelerated, the MI in the migratory zone of the otic wall is significantly higher than that in the rest of the otic epithelium. This suggests an intimate relationship between the migration of otic epithelial cells and a high rate of cell proliferation, the possible nature of which is discussed. Although the majority of mitoses in the otic anlage are located at the apical surface of the epithelium, from stage 13 onward, a few dividing cells are seen in the basal third of the epithelium. Furthermore, these basal mitoses appear exclusively in the migratory zone of the otic anlage, thus suggesting a possible relationship between epithelial cell migration and basal mitosis. During the developmental period prior to stage 18, no significant differences in mitotic spindle orientation are noted between migratory and nonmigratory zones of the otic anlage. In contrast, in stages of maximal otic epithelial cell migration (stages 19 to 21), the frequency of mitoses with the spindle axis oriented radially is significantly higher in the migratory zone. These findings point toward a close correlation between increased frequency of radial mitotic spindle orientation and intense cell migration, although the exact nature of this relationship is as yet unknown. PMID- 2592612 TI - Connections and frequency representation in the auditory brainstem of the mustache bat, Pteronotus parnellii. AB - The goals of this study were to describe the cochlear frequency map of the mustache bat, Pteronotus parnellii, and to relate the organization of cochlear primary afferents to that of the second-order projections from the cochlear nucleus to the superior olivary complex. Small deposits of horseradish peroxidase (HRP) were placed in the cochlear nucleus at sites that were physiologically characterized with respect to unit-best frequency. From the deposits, labeled fibers were traced in the retrograde direction to the cochlea and in the anterograde direction to the superior olive. Cochleas from both experimental and control animals were examined with light and electron microscopy. The peripheral axons of spiral ganglion neurons were counted in order to quantify the unusual variation in the innervation density along the cochlear spiral of the mustache bat. Regions of increased innervation density were found at the beginning and end of the basal turn of the cochlea. The highest cochlear innervation density consistently occurred in the upper basal turn. In horseradish peroxidase tracing experiments, this region contained labeled fibers only when HRP deposits were made at sites within the cochlear nucleus with unit-best frequencies around 60 kHz. These findings support the suggestion (Kossl and Vater, '85) that the cochlear sites of increased innervation density are related to the neural and behavioral emphasis that this echolocating bat places upon the analysis of the 60 kHz frequency band. The general arrangement of tonotopic maps within the cochlea, cochlear nucleus, and superior olive was consistent with previous observations in this bat and other mammalian species. At all three levels, there was evidence of a disproportionately large representation of frequencies around 60 kHz, similar to the enlarged representation reported within the inferior colliculus and auditory cortex of the mustache bat. In all cases there was a consistent relation between the size of the HRP deposit and the number and distribution of retrogradely labeled neurons in the cochlea. For most cases there was a similar relation between the size of the deposit and the terminal arborization field of anterogradely labeled fibers in the superior olive. However, in cases with deposits associated with the 60 kHz frequency band, the size of the labeled arborization field was more than twice as large as expected from the size of the deposits and from the extent of labeling in the cochlea. These cases suggest that the representation of frequencies around 60 kHz, already overrepresented in both the cochlea and cochlear nucleus, may be further expanded at the level of the superior olivary complex. PMID- 2592614 TI - Fate of descending interneurons in the metamorphosing brain of an insect, the beetle Tenebrio molitor L. AB - The fate of descending brain-thoracic neurons in the metamorphosing supraoesophageal ganglion of the mealworm beetle, Tenebrio molitor, is described. Comparison of the descending neurons of the larval, various pupal, and adult stages outlines a high degree of topological invariance in the structure of descending interneurons; i.e., the basic organization of the imaginal set of descending neurons is anticipated by the structure of the larval neurons. Single descending neurons of analogous clusters of larval and imaginal neurons outline a virtual identical structural organization in both the larval and imaginal brain. There is a quantitative increase from approximately 70 to approximately 120 brain thoracic interneurons during metamorphosis. This increase does not cause complex transformations in the structural organization of the descending interneurons. Experiments with the DNA-inhibitor hydroxyurea prove that the described topological invariant structure of the set of descending neurons is based on the persistence of individually descending neurons. There is evidence that the whole set of larval interneurons persists throughout the beetles' metamorphosis. The essential characteristics of the later imaginal set of descending neurons are qualitatively and quantitatively established within the first 10% of pupation. Structural invariance of the set of descending neurons is discussed with regard to the significance of cellular interaction for the mechanisms of metamorphic reorganization of nervous tissue. PMID- 2592615 TI - Fiber counts at multiple sites along the rat ventral root after neonatal peripheral neurectomy or dorsal rhizotomy. AB - We hypothesized that the afferent fibers in the ventral root of the rat are the third branches of dorsal root ganglion cells; these afferent processes in the ventral root are of varying length and end bluntly along the length of the root. In the case of an injury at either the central or the peripheral processes of the dorsal root ganglion cells in the neonatal stage, these fibers sprout at the blunt endings along the length of the ventral root. We cut either the sciatic nerve or the dorsal root on one side in neonatal rats. After the rats were fully grown, the number of both myelinated and unmyelinated fibers was counted in electron photomicrographs at multiple sites along the length of the ventral root. We observed a greatly increased number of unmyelinated fibers in the ventral root after the sciatic nerve had been cut at the neonatal stage. The magnitude of increase was more at the distal than at the proximal portion of the ventral root, suggesting that added fibers originated from the distal side. Neonatal dorsal rhizotomy, however, did not produce the same result. These results are consistent with our hypothesis that peripheral nerve injury at the neonatal stage triggers sprouting of the third branches of the dorsal root ganglion cells which end bluntly along the length of the ventral root in the normal animal. PMID- 2592616 TI - New structural features of synapses in the anteroventral cochlear nucleus prepared by direct freezing and freeze-substitution. AB - The rostral anteroventral cochlear nucleus (AVCN) of the chinchilla provides a preparation in which neuronal cell bodies and synapses in the mammalian central nervous system can be examined after direct freezing and freeze-substitution of rapidly excised brain stem slices. Cell bodies and synapses in the freeze substituted AVCN differed from those in perfusion-fixed AVCN in several interesting respects. Despite of these differences, four types of synaptic terminal were distinguished in freeze-substituted AVCN and correlated with the four well-known types of perfusion-fixed terminal. Since the transmitter at each of the four types of terminal has been tentatively identified, the structure of synaptic vesicles and junctions in the freeze-substituted terminals could be related to transmitter type. Synaptic vesicles were uniformly round, but their diameters, deployment, and related cytoskeletal elements near the synaptic junction differed in each chemical type of synapse; the synapses thought to be cholinergic, for instance, had only a few vesicles clustered at their presynaptic junctions while the rest of the vesicles were separated from the junction by a network of fine filaments. Two types of filamentous components, short vertical projections from the postsynaptic membrane and thin filaments protruding from these projections, comprised the basic structure of the postsynaptic specialization, but their sizes and distribution differed at each chemical type of terminal. For instance, the postsynaptic specialization at the glycine terminal was distinguished by numerous thin filaments which curved sideways to run parallel to the plasmalemma. Thus, freeze-substitution gives new information about structural differences between chemically different types of synapses, which may reflect differences in their transmitter storage, release, and reception. In addition, the AVCN preparation is of general interest in making cell bodies in the mammalian central nervous system available to the various structural and analytical techniques which depend on direct, rapid freezing. PMID- 2592617 TI - Neuronal localisation of neuropeptide Y gene expression in rat brain. AB - The cellular location of Neuropeptide Y (NPY) synthesis in rat brain is identified by using in-situ hybridisation histochemistry. The results show that NPY mRNA is widely distributed through the rat brain, although the levels of NPY mRNA are surprisingly low. There is a large degree of variation in the content of NPY mRNA in different regions. The highest cellular levels of NPY mRNA are found in the arcuate nucleus of the hypothalamus, in the hypothalamus, in the cerebral cortex, and in the hilar region of the hippocampus. In general, the distribution of perikarya containing NPY mRNA corresponds to the reported distribution of perikarya containing NPY-immunoreactivity. However, NPY mRNA was detected in the majority of the perikarya in the reticular nucleus of the thalamus, an area not previously known to contain NPY neurones. In many areas of the forebrain the distribution of NPY mRNA parallels that of somatostatin mRNA, supporting suggestions of their coexistence. The ability to detect NPY mRNA at the cellular level should be of considerable use in dynamic studies of the activity of NPY neurones. PMID- 2592618 TI - Distribution of muscarinic acetylcholine receptors on processes of isolated retinal cells. AB - Binding of propylbenzilylcholine mustard, a muscarinic acetylcholine receptor antagonist, to isolated retinal cells was examined with light microscopic autoradiography. Dissociation of the adult tiger salamander retina yielded identifiable rod, cone, horizontal, bipolar, amacrine/ganglion, and Muller cells. Preservation of fine structure was assessed with conventional electron microscopy. For all cell types, the plasmalemma was intact and free of adhering debris; in addition, presynaptic ribbon complexes were present in photoreceptor and bipolar axon terminals indicating that synaptic structures were retained. Specific binding to cell bodies and processes was analyzed separately by using morphometric and statistical techniques. The highest grain densities occurred on processes of amacrine/ganglion cells and axons and 2 degrees and 3 degrees dendrites of bipolar neurons. Bipolar cells, however, seemed to be a heterogeneous population because there was great variation in the density of binding sites on both their axons and distal dendrites. Intermediate levels of binding were found on bipolar 1 degree dendrites and horizontal cells. No specific binding was detected on Muller cells and most parts of photoreceptors. Comparisons between cells showed that grain densities were similar for bipolar axons and amacrine/ganglion cell processes but bipolar dendrites were richer in binding sites than horizontal cell dendrites. Thus, muscarinic receptors in the salamander retina are located on amacrine/ganglion, bipolar, and horizontal cells and primarily confined to the processes which compose the two synaptic layers. In the inner plexiform layer, muscarinic receptors reside on processes from all three inner retinal neurons: in the outer synaptic layer, receptors are only on second-order cells and are more numerous along bipolar than horizontal cell dendrites. PMID- 2592619 TI - Ascending unmyelinated primary afferent fibers in the dorsal funiculus. AB - The primary purpose of the present study is to obtain evidence as to the destination of the recently discovered unmyelinated primary afferent fibers in the mammalian dorsal funiculus. To do this rat dorsal roots were transected unilaterally from segments T8 or T9 caudally, and the numbers of axons were determined in the C3 fasciculus gracilis in normal animals and from both sides of the rhizotomied animals. In addition, C3 fasciculus gracilis counts were done in animals that had complete T6 or T10 spinal transections. The data indicate that there is an 80% loss of unmyelinated axons ipsilaterally and a 60% loss contralaterally in the fasciculus gracilis of the rhizotomied animals. These findings are interpreted as indicating that a significant fraction of the unmyelinated fibers in the fasciculus gracilis ascend, presumably to the nucleus gracilis in the brain stem, and also that a significant number of these fibers branch. We also provide evidence for contralateral myelinated primary afferent fiber projection in the fasciculus gracilis and show that the myelinated primary afferent fibers seem to be a more diverse population than the unmyelinated primary afferent fibers in the C3 fasciculus gracilis. PMID- 2592620 TI - Motor innervation of respiratory muscles and an opercular display muscle in Siamese fighting fish Betta splendens. AB - Horseradish peroxidase was used to identify motor neurons projecting to the adductor mandibulae, levator hyomandibulae, levator operculi, adductor operculi, and dilator operculi muscles in Siamese fighting fish, Betta splendens. These muscles participate in the production of respiratory and feeding movements in teleost fishes. The dilator operculi is also the effector muscle for gill-cover erection behavior that is part of Betta's aggressive display. The motor innervation of these muscles in Betta was compared to that previously described for carp. Motor neurons of the adductor mandibulae, levator hyomandibulae, and dilator operculi are located in the trigeminal motor nucleus, and motor neurons of the adductor operculi and levator operculi are located in the facial motor nucleus in Betta and in carp. The trigeminal motor nucleus in both species is divided into rostral and caudal subnuclei. However, there are substantial differences in the organization of the subnuclei, and in the distribution of motor neurons within them. In Betta, the rostral trigeminal subnucleus consists of a single part but the caudal subnucleus is divided into two parts. Motor neurons for the dilator operculi and levator hyomandibulae muscles are located in the lateral part of the caudal subnucleus; the medial part of the caudal subnucleus contains only dilator operculi motor neurons. The single caudal subnucleus in carp is located laterally, and contains motor neurons of both the dilator operculi and levator hyomandibulae muscles. Differences in the organization of the trigeminal motor nucleus may relate to the use of the dilator operculi muscle for aggressive display behavior by perciform fishes such as Betta but not by cypriniform fishes such as carp. Five species of perciform fishes that perform gill-cover erection behavior had a Betta-like pattern of organization of the caudal trigeminal nucleus and a similar distribution of dilator operculi motor neurons. Goldfish, which like carp are cypriniform fish and do not display, had a carp-like trigeminal organization and dilator operculi motor neuron distribution. PMID- 2592621 TI - Morphology of single primary vestibular afferents originating from the horizontal semicircular canal in the cat. AB - The central projections of physiologically characterized vestibular nerve fibers originating from the horizontal semicircular canal were studied in the vestibular nuclei of adult cats after intracellular staining with horseradish peroxidase (HRP). First, primary nerve fibers were physiologically classified as regular or irregular types on the basis of the regularity of the spontaneous discharge pattern. Then, these two types of fibers were morphologically analyzed and compared following HRP intraaxonal injection. The two types of axons showed a basically similar trajectory in the four major vestibular nuclei. They bifurcated into an ascending and a descending branch in the ventrolateral part of the lateral vestibular nucleus (LVN). The ascending branch extended rostrally and gave off one or two collaterals in the superior vestibular nucleus (SVN), although some of the ascending branches further ran rostrally into the cerebellum. The collaterals, while running medially, gave rise to fine terminal branches with en passant boutons in the SVN, and further coursing caudally, they entered the rostral part of the medial vestibular nucleus (MVN). The descending branch, while running caudally in the lateral part of the LVN and the inferior vestibular nucleus (IVN), gave off several thick collaterals to the MVN and extensive terminals were present in the IVN and MVN. In each primary axon, about one-third of the total terminal boutons were distributed in each of the SVN, the MVN, and the IVN. In contrast to this similarity of the overall axonal trajectory within the vestibular nuclei, both types of axons exhibited several marked differences in diameter and in the mode of terminal arborization. In almost every part of the ramification, the irregular-type fibers were thicker than the regular type fibers. In the regular-type axons, many small terminal boutons (mean size, 2.4 x 1.4 microns, N = 2,739) were located in close proximity (100-150 microns) to the parent collateral. In the irregular-type axons, slightly larger terminal boutons (mean size, 3.0 x 1.7 microns, N = 1,287), were spread more widely (200 300 microns) around their collaterals. These clear morphological differences between the regular-type and the irregular-type terminal axons were consistently observed in any vestibular nucleus. PMID- 2592622 TI - Distribution of nuclear pores and chromatin organization in neurons and glial cells of the rat cerebellar cortex. AB - Nuclear pores were assessed on freeze-fracture replicas from different neuronal and glial cell types of the rat cerebellar cortex. Nuclear diameter and perimeter were measured on semithin sections, and nuclear surface area and volume were calculated from these data. The proportion of inner nuclear membrane in apposition to condensed chromatin was measured on thin sections. The values of nuclear pore numerical density (number/micron2) were as follows (mean +/- S.D.): Purkinje cells, 22 +/- 3; Golgi cells 17 +/- 3; granule cells, 6 +/- 4; stellate and basket cells, 6 +/- 1; protoplasmic astrocytes, 11 +/- 1; Bergmann glia, 10 +/- 1; oligodendrocytes, 6 +/- 1. The total number of nuclear pores per nucleus varied from 18,451 +/- 2,336 (Purkinje cells) to 621 +/- 394 (granule cells) among neurons, and from 1,782 +/- 162 (protoplasmic astrocytes) to 402 +/- 67 (oligodendrocytes) among glial cells. The number of nuclear pores per unit nuclear volume (number/micron3), a parameter related to nucleocytoplasmic transport capacity, varied from 15 +/- 2 in Purkinje cells to 6 +/- 4 in granule cells. The proportion of nuclear membrane free of condensed chromatin was significantly (P less than 0.01) correlated to pore numerical density and total number of pores per nucleus. Some nuclear pores were associated in clusters of two or more pores. The amount of pore clustering was measured by counting the proportion of pores associated in clusters. This proportion varied among the different cell types from 82% in Purkinje cells to 44% in stellate and basket cells. The amount of pore clustering showed a positive linear correlation to pore numerical density and pore number per nucleus. However, the proportion of pores in clusters was not significantly correlated with the amount of condensed chromatin applied against the inner nuclear membrane. PMID- 2592623 TI - Cutaneous defects of focal dermal hypoplasia: an ectomesodermal dysplasia syndrome. AB - The 5 major cutaneous defects of development found in focal dermal hypoplasia, an ectomesodermal dysplasia syndrome, are: aplasia cutis congenita, multiform atrophy-like areas, striate, papillomatous, and lipomatous lesions of skin. Subepidermal lipomatosis, present in some lesions, has been reported to be due to absence of dermis or a striking underdevelopment of connective tissue with replacement by adipose tissue from herniation of subcutaneous fat through multiple areas of hypoplasia. We believe this theory to be a major error in interpretation of the microscopic findings. We have had the unique experience of studying 2 patients periodically for 27-30 years and 2 additional patients for a shorter time. Biopsy specimens were removed at intervals for analysis from the same or similar lesions (43 specimens) from these 4 individuals. Our evidence strongly supports the concept that the cutaneous defects of development involving fat cells represent heterotopic fat i.e. a fat nevus resulting from dysplasia, not hypoplasia followed by herniation of subcutaneous fat. PMID- 2592624 TI - Erythema nodosum-like lesions in Behcet's syndrome: a histopathologic study of 30 cases. AB - Thirty patients who fulfilled the criteria for complete and incomplete types of Behcet's syndrome were studied to determine the histopathologic changes of erythema nodosum-like lesions. Lymphocytic vasculitis was observed in 12 (40%) of the cases, but it was only focal in areas of severe lymphocytic inflammation and only mild in degree. No diffuse vasculitis was seen. It is our opinion that the observed lymphocytic vasculitis is only secondary to moderate or severe lymphocytic inflammation. Twelve cases (40%) revealed septal panniculitis, 10 cases (33%) demonstrated lobular panniculitis with moderate to marked inflammation and fat cell necrosis, and 8 cases (27%) showed mild and nonspecific inflammation in the panniculus. Therefore, there is a spectrum of histopathologic changes of erythema nodosum-like lesions in Behcet's syndrome, similar to that of erythema nodosum secondary to other systemic disorders. PMID- 2592625 TI - Expression of an estrogen receptor-associated protein (p29) in epithelial tumors of the skin. AB - p29 is a cytoplasmic serine phosphoprotein of 29 kD MW, closely linked to estrogen receptors. In this work we studied the expression of p29 protein in normal human skin and a group of cutaneous benign and malignant tumors by using a monoclonal antibody (ERD5) that specifically recognizes p29. In normal skin, p29 reactivity was observed in epidermal and some adnexal keratinocytes, as well as in smooth muscle cells of dermal arterioles and arrector pili muscles. p29 was also detected in most, but not all, epithelial tumors studied. The expression of p29 was generally stronger in the more differentiated (keratinized) normal and neoplastic keratinocytes; however, no correlation could be noted between immunochemical staining for p29 and either benignity of the lesion or sex of the patient considered. Whereas, in breast cancer, the expression of p29 is reported to correlate with endocrine response, the precise relationship between epithelial tumors of the skin and the action of estrogens remains to be elucidated. PMID- 2592626 TI - Xanthomatous infiltrate of the face. AB - We report 2 cases which shared an unusual histopathologic pattern of a xanthomatous infiltrate occurring on the nose. Both patients were women in their fifth decade. Each presented to the dermatology clinic with multiple soft, flesh colored papules, up to 1 cm, in diameter on the lateral aspects of the nose. The lesions had been present for several years. Both patients were otherwise completely well, and asymptomatic. In one case, focal telangiectasia and central umbilication was noted, and the clinical differential diagnoses included basal cell carcinomas and appendageal tumors. In each case, a biopsy was performed. The lesions appeared histologically quite similar. The epidermis was unremarkable. Within the dermis, there was a mid-reticular dermal infiltrate of macrophages with unilocular and multilocular fat laden cytoplasm, and scalloped nuclei. Only a scant inflammatory infiltrate of lymphocytes and histiocytes was present. Minimal dermal fibrosis was also present. We believe that xanthomatous infiltrate of the face is a distinct clinical entity which presents as multiple flesh colored papules on the nose, which have a characteristic histologic appearance of abundant lipid-laden macrophages within the dermis. PMID- 2592628 TI - Abstracts of papers presented at the 27th annual meeting of the American Society of Dermatopathology. San Francisco, November 29-December 1, 1989. PMID- 2592627 TI - "Immature" trichoepithelioma. PMID- 2592629 TI - Feeding calcium soaps of fatty acids to lactating cows: effect on production, body condition and blood lipids. AB - Ca soaps of fatty acids (CSFA, 0.5 kg/d) were added to the diet of lactating cows for 170 d, and production, body condition score and blood lipids were examined. Production of fat-corrected milk was increased by 1.5 kg/d owing to increase in both milk and fat production. Over 250 d lactation, production of fat-corrected milk was enhanced by 1.3 kg/d. Body condition scores were lower in cows fed CSFA in early lactation, but tended to exceed those of control cows after 80 d lactation. Reproductive performance was improved in cows fed CSFA. Serum total lipids, phospholipids and cholesterol were increased in CSFA cows at 15 and 29 d but not at 59 d post partum. The cholesterol increase was mainly in the high density lipoprotein fraction. PMID- 2592630 TI - Effect of udder preparation on transmission of Staphylococcus aureus while milking with a multi-valved cluster. AB - With two groups of 12 cows, a procedure involving foremilking, teat washing and drying before milking was compared with no premilking preparation for its effects on mastitis and teat contamination. Half the cows in each group were deliberately infected in a single udder quarter with Staphylococcus aureus and milked alternately with uninfected cows for 9 weeks. To minimize transfer during milking all cows were milked with the use of a multi-valved claw. Five new staphylococcal infections developed in the 12 animals in the teat preparation group compared to one in the control group. A significantly higher incidence of teat orifice colonization developed in the prepared cows compared to the control cows (17 v. 7). Foremilking and teat preparation led to transfer of staphylococci between quarters (within cow) but this was effectively prevented by the multi-valve claw in the absence of teat preparation. PMID- 2592631 TI - Lipase redistribution in cows' milk during induced lipolysis. I. Activation by agitation, temperature change, blood serum and heparin. AB - Effects of agitation, temperature change, blood serum and heparin on lipolysis and on distribution of lipoprotein lipase (LPL) in cold-stored cows' milk were measured. All individual milks (n = 135) were susceptible to activation treatments. With 'gentle' treatments, induced lipolysis was strongly correlated to spontaneous lipolysis (r greater than or equal to 0.74). In contrast, induced lipolysis in response to 'vigorous' treatments was more variable (0.7 greater than r greater than 0.34) and levelled off in milks with high spontaneous lipolysis. Induced lipolysis always resulted from an increase in LPL associated with cream. Strong correlations (0.79 less than or equal to r less than or equal to 0.94) were found between free fatty acid levels and cream LPL. All treatments (except heparin addition) also promoted lipolysis/unit cream LPL. PMID- 2592632 TI - Lipase redistribution in cows' milk during induced lipolysis. II. Activation by milk pH adjustment. AB - Cold-stored milk lipolysis was enhanced from 5- to 50-fold when milk pH was adjusted to 7-8 with NaOH, while it was greatly decreased or stopped by an adjustment to pH 6-5.5 with citric acid. Small adjustments in pH (less than or equal to 0.5 pH unit) also affected lipolysis, but the pH of native milk was not related to spontaneous lipolysis. The binding of lipoprotein lipase to cream was a pH-dependent process with an optimum near pH 7.0. Activity of the cream lipase on cold-stored milk fat continuously increased from pH 6.6 to pH 8.5. The activating effect of heparin on cold-stored milk lipolysis reached a maximum at pH 7.0-8.0 and a minimum in native milk, while addition of blood serum gave an opposite response. PMID- 2592633 TI - The effects of school, family, self-concept, and deviant behaviour on adolescent suicide ideation. AB - In this study of a population of junior and senior high school students in a mid sized, Western city, adolescent emotional and ideological disparity with parents and disparity between the importance the adolescent placed on academic achievement and satisfaction with academic achievement were linked to suicide ideation through the intervening variables of self-esteem, purpose in life, and two forms of deviant behaviour--alcohol use and eating disorder. Self-confidence and the deviant behaviours of delinquency and drug use did not prove to be meaningful intervening variables. PMID- 2592634 TI - Targets of communication during adolescence. AB - The purpose of the study was to investigate targets of communication during adolescence. Turkish high school students between the ages of 12 and 18 were asked to rank order a maximum of five people with whom (a) they enjoyed talking with the most, (b) they were most intimate with, and (c) they talked with the most frequently. It was found that the same sex friend and the mother were the preferred targets of communication for both sexes. Also, with increasing age, more friends and less family were cited by both sexes, but the trend was more prevalent for males. PMID- 2592635 TI - Marriage by arrangement: a metaphor for one particular use of network therapy. AB - This paper uses the metaphor of the wedding in an arranged marriage to describe the process of using a network meeting to overcome resistance and engage a hostile adolescent and her family in a residential treatment programme. A review of the literature is followed by a description of the clinical case. Finally, practical and theoretical issues are discussed. PMID- 2592636 TI - The relationship of ego identity to social network structure and function in young men and women. PMID- 2592637 TI - Seasonal variations in the child and adolescent psychoses. AB - We examined seasonality effects in a controlled study of children and adolescents with psychotic states. There was a peak of psychotic births between February and March but this pattern did not differentiate psychotics from psychiatrically disturbed controls. Onset of illness was found to be significantly more common in the summer months (June to August) in psychotics than in controls. We discuss possible explanations for this phenomenon. PMID- 2592638 TI - Social cognitive skills and behavioural adjustment of delinquent adolescents in treatment. AB - Social cognitive skills (i.e. problem-solving, self-control, locus of control, rational attributions) were examined in aggressive and non-aggressive delinquent youths at two levels of behavioural functioning (high versus low). Behavioural functioning was defined in terms of the youths' standing within a 10-level behavioural token economy programme. Inventories and questionnaires were used to measure the skills of interest. A significant interaction was found on problem solving skills, with higher functioning, non-aggressive youths performing better than their lower functioning counterparts, while no differences occurred within the aggressive groups. No differences were obtained on the other measures. PMID- 2592639 TI - Disordered eating in South-western Pueblo Indians and Hispanics. AB - The present study investigated the incidence of eating disorders in two samples representing populations seldom reported upon in the eating disorder literature: Pueblo Indians and Hispanics. Subjects were 95 students from a rural, public high school serving primarily low income families. Although no ethnic differences were found, the majority of girls in both samples reported wanting to lose weight, being worried about their weight, and indulging in binge eating. Nine of the girls (11 per cent) reported eating habits consistent with the DMS III (APA, 1980) criteria for bulimia. In contrast, few boys indicated concerns about their weight or eating habits. The results suggest that eating disorders and concern about obesity are found in a variety of ethnic groups in the United States today. PMID- 2592640 TI - Carotenoids and retinoids in Finnish foods: dairy products and eggs. AB - As part of an overall composition study of Finnish foods, the carotenoid and retinoid content of 20 dairy product samples and eggs were determined by HPLC. The total beta-carotene (all-trans beta-carotene plus 15-cis beta-carotene) was quantitated for dairy products. For egg and egg yolk, lutein content was also determined. Only traces of lycopene, cryptoxanthin, and alpha-carotene were present. All-trans retinol and 13-cis retinol were the major retinoids in dairy products. Small amounts of 9-cis, 11-cis, and 9,11-cis retinols were found. High values of both retinol and beta-carotene were found in full fat cheeses and whipping cream: from 179.0 (cheese, Edam-type) to 318.7 micrograms/100 g (whipping cream) and from 86.7 (cheese, Edam-type) to 186.5 micrograms/100 g (whipping cream) for all-trans retinol and total beta-carotene, respectively. The retinol content averaged 16.3, 32.6, and 52.2 and that of beta-carotene 9.6, 16.7, and 3.0 micrograms/100 g in milk (1.9% fat), milk (3.9% fat), and human milk, respectively. The major pigment in eggs and egg yolk was lutein, 619.5 micrograms/100 g in eggs and 1575.8 micrograms/100 g in egg yolk. According to this study, at the present level of consumption in Finland, milk, milk products (excluding butter), and eggs result in a daily intake of about 350 retinol equivalents, and consequently, are a major source of vitamin A. PMID- 2592641 TI - Growth and production of enterotoxin A by Staphylococcus aureus in cream. AB - Behavior of Staphylococcus aureus strains 100-A, 196-E, 254, 473, 505, and 521 in sweet (18 to 80% milk fat) and neutralized sour cream was studied. Cream was inoculated to contain approximately 10(3) to 10(4) S. aureus/ml, depending on milk fat content, and was incubated at 4, 22, or 37 degrees C. Determinations were made of aerobic plate count, S. aureus count, and pH. When growth in cream exceeded 10(7) S. aureus/ml, enterotoxin analysis was done. Sweet and neutralized sour cream supported growth of all strains of S. aureus tested. Strains 100-A, 196-E, 473, 505, and 521 grew sufficiently to produce enterotoxin in sweet cream of 18 or 32% milk fat held at 37 degrees C for 18 h or at 22 degrees C for 52 h. Populations of strains 100-A, 196-E, 505, and 521 exceeded 10(6) cells/ml in sweet cream of 36% milk fat held for 18 h at 37 degrees C. Strains 100-A and 521 grew to more than 10(6) cells/ml in sweet cream of 40% milk fat held for 18 h at 37 degrees C. No strain of S. aureus grew to levels associated with detectable enterotoxin production at 4 degrees C within 14 d in any cream. Incubation temperature, milk fat content of cream, and variation among strains influenced the ability of S. aureus to grow and produce enterotoxin. PMID- 2592642 TI - Milk production in lactating buffalo receiving recombinantly produced bovine somatotropin. AB - Thirty healthy Murrah buffalo (Bubalus bubalis) in their second to fourth lactations were selected from the herd at the National Dairy Research Institute, Karnal, Haryana, India, for use in a 35-d study to determine the effects of recombinantly produced bovine somatotropin on milk production, milk composition, and dry matter intake. Treatments were daily injections of 0, 25, or 50 mg somatotropin per animal for 14 d. All buffalo consumed green chopped fodder ad libitum plus a predetermined quantity of concentrate mixture to each animal, based on individual milk production during the 14-d pretreatment period. The quantity of concentrate mixture fed to each buffalo was not altered during the study. Net increase in milk volume for groups receiving 25 and 30 mg somatotropin was 16.8 and 29.5% over controls. Milk composition, DM intake, and body weights were not affected by treatment. PMID- 2592643 TI - Effect of hydrogenated fat on feed intake, nutrient digestion, and lactation performance of dairy cows. AB - Eight lactating Holstein cows were fed four diets in a replicated 4 x 4 Latin square design to determine how hydrogenation affects fats as supplements for dairy rations. Four isonitrogenous diets contained either no added fat, 5% yellow grease, or 3 or 5% hydrogenated yellow grease. Only yellow grease reduced DM intake compared with DM intake of the control diet. Diets supplemented with fat had lower digestibilities of fiber, nitrogen, energy, and fatty acids than the control diet did. Ruminal acetate concentration and acetate to propionate ratio were higher for the hydrogenated fat than for yellow grease. However, fatty acid digestibilities were lower for diets containing hydrogenated fat. Milk yields of fat-supplemented diets, whether actual or 4% FCM, did not exceed the control diet except for 5% hydrogenated yellow grease. This study shows that hydrogenated fats have fewer negative effects on food intake, milk fat content, and ruminal fermentation but have lower digestibilities than other fats. Hydrogenation improved milk yield compared with yellow grease fed at the same amount of supplementation. PMID- 2592644 TI - Microbial inoculation of alfalfa haylage: ensiling characteristics and milk production response when fed to early lactation dairy cows. AB - Third-cutting alfalfa hay harvested at bud stage and wilted to approximately 65% moisture was treated with a live bacterial inoculant at the rate of 300,000 cfu/g fresh alfalfa. Treated alfalfa was packed in polyethylene bags. Samples were taken at time of ensiling and d 1, 2, 3, 4, 7, and 28 postensiling. Mean pH was lower in the treated haylage (5.09 and 5.71 for treatment and control, respectively). Mean temperatures were higher in the treated haylage (30.0 and 28.0 degrees C for treatment and control, respectively). Mold count, water soluble carbohydrate, alpha amino nitrogen, CP, and ADF were not affected by treatment. Regardless of treatment, pH, mold counts, and water-soluble carbohydrates declined with time. There was no significant difference between treatments for DM intake, milk production, and milk composition. PMID- 2592645 TI - Effect of copper loading of preruminant calves on intracellular distribution of hepatic copper, zinc, iron, and molybdenum. AB - The subcellular distribution of Cu, Zn, Fe, and Mo was investigated in liver homogenates from preruminant calves fed control Cu (10 ppm), high Cu (1000 ppm), or high Cu plus high Zn (1000 ppm) milk replacer. For controls, Cu was located primarily in the nuclei and large granule fractions, Zn mainly in the cytosol, and Fe in the cytosol and nuclei fraction; Mo was present in all compartments but least in microsomes. Calves fed high Cu had markedly increased hepatic Cu concentration in the nuclei and cytosol fractions, reduced cytosol Zn, increased nuclei Fe, and decreased Mo concentration in all cell compartments. Feeding high Zn with high Cu (which prevented deaths from high Cu) reversed some changes in hepatic trace element patterns caused by high Cu while initiating new alterations. The marked increase in hepatic Cu and reduced Mo in nuclei and cytosol after Cu loading indicate that these compartments may have a predominant role in the development of Cu toxicity in the preruminant calf. PMID- 2592646 TI - Dinitrochlorobenzene contact hypersensitivity as a marker trait for selection to improve disease resistance in calves. AB - Measurements of double skin fold thickness (mm) were used to assess the feasibility of use of cutaneous delayed-type hypersensitivity response as a marker trait to select for genetically improved disease resistance. Data were from a sample of 149 7-wk-old Holstein calves, from 15 sires, that previously had been sensitized to the contact allergen dinitrochlorobenzene. Response was monitored 24 and 48 h postchallenge. Analysis was by least squares according to a model that included fixed managerial effects, disease prevalence, and severity categories and sire of calf. Double skin fold thickness increased about 50% by 24 h, followed by a 4% decrease between 24 and 48 h. Season of birth was the only consistently significant fixed effect. Calves born in fall showed larger skin changes at each stage of response than calves born in spring. Restricted maximum likelihood estimates of paternal half-sib heritability were moderate to high for all stages of response, and phenotypic and genetic correlations between stages were significant and positive. Although the prevalence and severity of naturally occurring pneumonia and diarrhea did not significantly affect quantity of response, there is need to study further this relationship for intracellular pathogens. Delayed-type hypersensitivity response to dinitrochlorobenzene can meet requirements for a successful marker on which to base sire selection for disease resistance, if it is related to economically important, intracellularly characterized, pathogenic bovine diseases. PMID- 2592647 TI - Modeling net energy efficiencies as quantitative characteristics in lactating cows. AB - To date, researchers have measured net efficiencies of energy conversion using data from animals in energy chambers. The expense of this approach prevents the establishment of a large data base for quantitative studies. Our purpose was to investigate models that would enable us to use data collectable in normal field conditions to compare dairy cattle for their net energetic efficiency. Data from 357 Holstein cows in seven herds and in various parities consisted of daily measures of DM intake, net energy intake, milk production, biweekly measures of milk components, and bimonthly BW. Eighteen alternative multiple regression models were fitted to each of the cows to estimate simultaneously net efficiency of energy conversion for maintenance, lactation, pregnancy, and BW change during positive energy balance period, negative energy balance period, and whole lactation. Results from several fitted models approximated closely literature results based on data from cows in energy chambers. These comparative results suggest that it is possible to estimate efficiency of energy conversion on individual cows using data obtained from normal animal management situations. PMID- 2592649 TI - Relationships between characteristics of herd of bull-dams and predicting transmitting ability of young bull. AB - Young bulls selected from Michigan herds for sampling by Select Sires Incorporated from 1975 to 1982 were identified. Data for herds from which young bulls were selected for year of young bull's birth were acquired from the Michigan DHIA. Herd average milk production, intraherd standard deviation for milk production, coefficient of variation for milk production, average sire transmitting ability of cows in the herd, and intraherd standard deviation of sire transmitting ability were computed for each herd. These herd characteristics were used in prediction of young bull transmitting ability. When considered along with a pedigree index predictor, intraherd standard deviation for milk production was significant in prediction of young bull transmitting ability, but other herd characteristics were not. Young bulls were grouped by the intraherd milk variance of the herd from which they were selected. Evaluations based on progeny tests showed young bulls selected from herds with low intraherd milk variance were genetically superior to those selected from herds with high intraherd milk variance. Predicted transmitting abilities for young bulls selected from low variance herds were less biased, but predicted transmitting abilities for those selected from high variance herds were inflated. However, the variance of biasedness was slightly lower in higher variance herds. PMID- 2592648 TI - Estimation of genetic parameters for production and reproduction in Finnish Ayrshire cattle. AB - Records of AI-sired cows born between 1978 and 1982 were used to form two composite production and reproduction data sets. First (second) consisted of 35,568 (26,443) first lactations of daughters of 270 (237) sires. Traits were FCM, heifer, and first parity nonreturn rates, days between calving and first insemination, and days open, with means 5075 (5280) kg, .62 (.62), .44 (.49), 81 (81) d and 110 (111) d. (Co)variance components were estimated by REML with an expectation maximization algorithm. Sire model included age, month, herd-year effects, and relationships among sires. Records on animals with observations missing on some traits were included. Estimates of heritabilities, averaged over data sets, were nonreturn rates for heifers and for cows, .02; FCM, .32; days to first insemination, .19; and days open, .10. Genetic correlations between first parity fertility and yield were unfavorable; the highest, .43, was between FCM and days open. Heifer nonreturn rate had a .09 correlation with production and a .26 correlation with cow nonreturn rate. Phenotypic correlations were in the same direction as genetic correlations but were smaller in magnitude. Results suggest that selection only for production would cause deterioration in level of fertility. When economical, AI sires should be evaluated for daughter fertility. A multi-trait model including milk production, days open and relationships among bulls is recommended for genetic evaluation. PMID- 2592650 TI - Effects of body measurements and weight on calf size and calving difficulty of Holsteins. AB - Body measurements (heart and paunch girths, wither height, chest depth, pelvic length and width, and body length), body weight, and calving evaluation data (calf birth weight, calf sex, calf presentation, and calving assistance needed) were collected from 1974 parities of 762 Holstein cows between 1968 and 1986. Degree of calving assistance was scored continuously from 1 (no assistance) to 10 (hard mechanical assistance). Phenotypic correlations of dam body traits with calf birth weight were all significantly positive when combined for all parities and ranged from .23 for paunch girth to .27 for body weight and heart girth. Correlations of dam body traits with calving assistance scores were all significantly negative across parities and ranged from -.24 to -.30. Correlations of calf birth weight with calving assistance were higher for first parity (.37) than for all parities (.20). Least squares analysis showed that cows with shorter wither height and shorter pelvises tended to require more calving assistance. Heavier calves, winter calvings, and earlier parity all were related to increased dystocia. Male calves were heavier than female calves and also were associated with greater calving difficulty. PMID- 2592651 TI - Animal model evaluation of dairy goats for milk, fat, and protein yields with crossbred animals included. AB - Genetic evaluation of dairy goats was extended to include evaluation of protein yield and evaluation of Oberhasli and experimental breeds. Diverse genetic background of parents of crossbred animals can be accounted for with an animal model that includes all relationships. The animal model system implemented for dairy goats differed from the one for dairy cattle in that all breeds were processed simultaneously and evaluations of relatives included data from does without a first lactation record and from later herds for does that changed herds. Unknown parent groups were defined for each breed except Oberhasli, which was grouped with the Alpine breed because of small population size. Management groups were 2-mo seasons with separate groups for first and later lactations. Management groups with fewer than five lactation records were combined with other groups until five lactations were included or the management group was 10-mo long. Evaluations for milk and fat were computed for 141,003 animals: 80,227 does with lactation records, 34,294 dams without records, and 26,482 bucks. About 70% of animals had protein evaluations. Genetic trend in 1984 for the five breeds with largest population sizes ranged from 3.8 to 5.2 kg/yr for milk yield. PMID- 2592652 TI - Association between neutral-to-earth and cow contact voltage on New York dairy farms. AB - Cow contact (or "stray") voltage has been associated with various health and management problems in dairy cows. Neutral-to-earth voltage (voltage between the service entrance neutral bus and a reference ground rod) has been equated with cow contact voltage in previous research. To investigate the association between these two voltages, single ("instantaneous") and continuous voltmeter measurements were made at 97 farms in New York. A small positive correlation was found between all single neutral-to-earth and cow contact measurements. Eleven farms with continuous neutral-to-earth readings of .5 V or greater were resurveyed. Eight of the resurveyed farms showed a small or nonexistent correlation between the two voltages. Neutral-to-earth voltage is not recommended as an indicator to predict the presence or magnitude of cow contact voltage. PMID- 2592653 TI - Effect of inoculation rate of selected strains of lactic acid bacteria on fermentation and in vitro digestibility of grass-legume forage. AB - Grass-legume forage was used to evaluate the effect of inoculation rate of selected strains of lactic acid bacteria on fermentation and in vitro digestibility during 57 d of ensiling. Chopped forage (DM = 28%) was ensiled in 4 to 6-kg quantities and treated as: 1) control, 10(3) epiphytic lactic acid bacteria; 2) 10(5) added lactic acid bacteria; and 3) 10(6) added lactic bacteria/g of wet forage. Samples were obtained for analyses on d 0, 1, 2, 3, 6, 10, 14, 29, and 57 of fermentation. Treated silages were observed to have: 1) greater quantities of lactic acid bacteria, 2) a greater proportion of homofermentative lactic acid bacteria, and 3) lactic acid bacteria with greater biological activity. Addition of each amount of lactic acid bacteria: 1) increased the rate of utilization of water-soluble carbohydrate and decline in pH, 2) limited the formation of NH3 N, and 3) increased the in vitro digestibility of DM and ADF. No differences were observed in the lactic acid content of the silages after 57 d of fermentation. PMID- 2592654 TI - Deactivation of tannin in high tannin milo by treatment with urea. AB - Experiments were conducted to determine the effectiveness of urea in deactivating tannin in high tannin milo. High tannin milo (Pioneer B 815, 3.4 +/- .3% tannin) was reconstituted with aqueous urea solutions to give combinations of 26, 30, and 34% moisture with 2, 3, and 4% urea (percentage of urea per dry weight of milo). All treatments were maintained at 25 degrees C and were effective in deactivating tannin with no differences among moisture or urea content. The average rate of tannin deactivation was 68 +/- 2% d-1. Temperature affected rate of tannin deactivation in milo reconstituted to 30% moisture and 3% urea when stored at 25 or 60 degrees C. Rate of tannin deactivation was 44 +/- 5 and 89 +/- 18% d-1 at 25 and 60 degrees C, respectively. Tannin in high tannin milo can be deactivated rapidly and completely by reconstitution with aqueous urea. These studies demonstrate that tannin is deactivated completely under conditions where urea is an effective preservative of high moisture milo. PMID- 2592655 TI - Dental education 1989: how are we adapting to change? AB - Multiple pressures on the nation's dental schools have come in the form of a declining applicant pool, new university expectations of scholarship, and a changed professional environment for the dentist. The declining applicant pool led to a first-step response: declining enrollments. Schools are now moving to a new phase in which they must cope with severe fiscal pressures simultaneously with developing new programs to equip the dentist for the changed professional environment. Factors in the new environment for dentistry are discussed, including changing demography and distribution of disease, new technology, and the changed marketplace. Fiscal survival options are reviewed, as are emerging differences between public and private schools. The recent experience of five schools seeking to adapt to fiscal and environmental pressures is described, and six criteria are suggested as useful in measuring the success of these (and other) schools. Crucial issues are discussed from the perspective of the dental school and the university. The value of the dental school as a major resource for the university is stressed, as is the important role of university administrators in providing the necessary conditions for schools that must change. PMID- 2592656 TI - Current implications of dental school-based AEGD programs for institutions, the profession, and society. PMID- 2592657 TI - Gender differences in item performance and predictive validity on the DAT Quantitative Reasoning Test. AB - This article reports on examination of the performance of males and females on individual items of a graduate admission mathematics test--i.e., the Quantitative Reasoning Test administered as part of the Dental Admission Test--and relates the results to success in dental school. Items that are differentially familiar to males and females were identified and used as independent predictors of success in the first year of dental school. There was no significant difference between male and female performance in dental schools and no significant difference in the predictive validity of items that "favor males" and those that "favor females." Furthermore, the items that "favor females" produce approximately equal raw score distributions for males and females without significant adjustments in the content specifications of the test and thus would not underpredict female performance in dental schools. PMID- 2592658 TI - Dental hygienists' anti-tobacco role: educational perspectives. AB - Dental hygienists need to assume a proactive health education role concerning tobacco use. To help measure, define, and broaden this role, a study was conducted to assess dental hygienists' current clinical practice behaviors, attitudes, and perceived curriculum adequacy concerning anti-tobacco efforts. The relationships among these variables and respondents' academic degree and year of graduation were analyzed. The study population consisted of a proportionate random sample of 500 dental hygienists in five states and the District of Columbia. A self-administered questionnaire yielded a response rate of 79.4 percent. Based on chi-square analyses of individual items, it was found that, when controlling for degree held, year of graduation was not significantly related to clinical practice behaviors or attitudes, but was significantly related to the majority of curriculum adequacy items. Academic degree, when controlled for year of graduation, was not significantly related to clinical practice behaviors, but was related to one attitude and two curriculum adequacy items. Analysis of variance and Duncan's multiple range test revealed the following significant relationships for aggregate data: year of graduation and degree held appeared to have no relationship to aggregate clinical practice behaviors or attitudes, M.S. degree respondents assigned higher curriculum adequacy ratings than did other subjects, and respondents who graduated prior to 1972 assigned their curricula more negative adequacy ratings than did all other graduates. The most recent graduates rated their curricula the most positively. The study's overall findings suggest that a fairly well-developed role for dental hygienists in anti-tobacco efforts exists. Given the current emphasis on health promotion, prevention, and holism in the provision of oral health care, it is commendable, but not surprising, that dental hygiene programs appear to have made positive modifications over time in tobacco-related content. PMID- 2592659 TI - Perceptions of stress among third-year dental students. AB - The purpose of this study was to identify the perceived stress of third-year dental students using a large sample (four classes). The dental environmental stress (DES) questionnaire was administered to 263 (87.7 percent) third-year students from 1984 to 1988. The top six stress items, as perceived by third-year students, included examinations and grades, graduation requirements, inconsistency of professor's feedback, patient tardiness or no show, atmosphere created by clinical faculty, and financial responsibilities. In addition, 15 of the 38 DES questionnaire items were considered moderately stressful or very stressful by at least 34.0 percent of the students. PMID- 2592660 TI - Attitudes of operative dentistry faculty toward rubber dam isolation. PMID- 2592661 TI - Training general practice residents in patient behavioral management. PMID- 2592662 TI - Task force on innovation in dental hygiene curricula. PMID- 2592663 TI - A new scalpel handle for the cutaneous surgeon. AB - A newly designed scalpel handle that bridges the gap between a standard #3 and a Beaver handle is presented. PMID- 2592664 TI - Bulbous-lysing underminers. AB - The blunt dissection offered by liposuction cannulas has greatly aided surgical undermining such as in face-lift surgery. Herein, we propose a new line of instruments that combines bulbous or blunt dissection with intervening lysing segments. The subgaleal version enables the surgeon to quickly undermine the scalp from ear to ear for scalp reductions in the subgaleal plane. In addition, the subgaleal device aids in the maintenance of the proper dissection plane and is useful in browlifts as well. A closely related "general" undermining device greatly facilitates face-life surgery and has found other uses in the undermining or separation of fibrous tissue planes. PMID- 2592665 TI - Board certification and subcertification in cosmetic surgery: how to qualify and what to study. PMID- 2592666 TI - Exogenous electric current can reduce the formation of hypertrophic scars. AB - Exogenous electric current has been shown to influence the healing of wounds in both human subjects and animal models. We examined the effect of positive polarity electrical stimulation on the resultant scar thickness of surgically induced wounds, and report that electrotherapy can reduce scar thickness and hypertrophic scar formation. PMID- 2592667 TI - Electrosurgical treatment of etretinate-resistant Darier's disease. AB - Two patients with symptomatic, etretinate-resistant, intertriginous Darier's disease were successfully treated with deep split-thickness skin excision using an electrosurgical unit. Healing was rapid and recurrence of disease has been minimal. The use of electrosurgery appears superior to other surgical techniques because, with the ease of hemostasis, the surgeon can more easily control the depth of excision and treat intertriginous creases. PMID- 2592669 TI - The "modified vertical mattress". PMID- 2592668 TI - Basal cell carcinoma and infundibuloma arising in separate sebaceous nevi during childhood. AB - Sebaceous nevi usually occur as solitary hamartomas, located either on the scalp or on the face. Their clinical importance in dermatology stems from their propensity to develop secondary tumors, particularly basal cell carcinoma. In general, malignant transformation does not occur until postpubertal life. We report a case of a 9-year-old girl with a basal cell carcinoma arising from a sebaceous nevus on the scalp, and an infundibuloma arising from a separate sebaceous nevus on the right side of the face. PMID- 2592670 TI - Pigmented BCC and LMM in a single lesion. PMID- 2592671 TI - Strategies for resolving the heterogeneity of schizophrenics and their relatives using cognitive measures. AB - The resolution of the heterogeneity of schizophrenics and their relatives using cognitive tasks requires measures of individual differences--usually of differential ability, which is inferred from differential performance. Tasks that are suited for establishing a group's differential ability are often unsuited for measuring individual differences. The problem is that for any group for which Tasks A and B have different mean accuracy, the (A - B) difference scores of individual subjects have an artifactual curvilinear relation to (A + B) overall accuracy, with the largest (A - B) scores occurring at about 50% (A + B) overall accuracy for a dichotomously scored free-response task. Two possible solutions are (a) to convert Task B scores to residualized scores, using the regression of Task B scores on Task A scores as determined for normal subjects; or (b) to titrate overall (A + B) accuracy of each subject to a constant level by manipulating a variable. PMID- 2592672 TI - Fear-relevant selective associations and covariation bias. AB - Three experiments used an illusory correlation paradigm to assess the effects of fear on the perception of the covariation between fear-relevant stimuli and shock. In Experiment 1, high- and low-fear women were exposed to 72 trials during each of which a fear-relevant (snake or spider) or fear-irrelevant (mushroom and flower) slide was followed by a shock, a tone, or nothing. Although the relation between slide types and outcomes was random, high-fear subjects markedly overestimated the contingency between feared slides and shock. Experiment 2 showed that this bias was due to the aversive, rather than more generally salient, features of shock. Low-fear subjects demonstrated biases equivalent to those of high-fear subjects only when the base rate of shock was increased from 33% to 50% in Experiment 3. It is concluded that fear may be linked to biases that serve to confirm fear. The relevance of the present findings to preparedness theory is also discussed. PMID- 2592673 TI - Fear conditioning, meaning, and belongingness: a selective association analysis. AB - Twenty-three subjects rated the belongingness of pairs of conditionable (photographic slides) and unconditioned (e.g., shock, tone, human scream) stimuli. Forty new subjects were then classically conditioned, using rating defined high (angry face/scream) and low (landscape/scream) belongingness pairs. Finger-pulse responses to the high-belongingness pairs showed superior acquisition and resistance to extinction. Another 40 subjects were conditioned to compound stimuli: a slide (either landscape or angry face) that was the same over trials, and a yellow or blue background that was the discriminant cue for the unconditioned stimulus (scream). When the angry face (the high-belongingness slide) was the invariant part of the compound, relatively poorer differential pulse-volume and skin-conductance conditioning was observed. Thus, depending on the task, a priori belongingness rendered stimuli selectively conditionable, either enhancing or inhibiting visceral response associations. PMID- 2592674 TI - A prospective study of stressful life events and schizophrenic relapse. AB - In this prospective, longitudinal study, 11 recent-onset schizophrenic outpatients who met criteria for psychotic relapse or significant psychotic exacerbation during a 1-year period of standardized maintenance medication, and 19 patients who did not relapse during this follow-up period, were interviewed monthly regarding life events. As hypothesized, for relapsing patients, a significantly higher number of independent life events (those not the result of symptomatology or personal influence) occurred in the month preceding relapse. This increase was apparent relative to either the analogous month of a "nonrelapse" period in the same patient or the average number of independent events per month during a 1-year standardized medication period for nonrelapsing patients. The methodological advances of this design as well as the consistency of these findings with those of previous retrospective studies supports the hypothesis that life events may sometimes "trigger" schizophrenic episodes. PMID- 2592675 TI - Restrained eating: an experimental disentanglement of the disinhibiting variables of perceived calories and food type. AB - The influence of food type on the restrained eating pattern was examined. In Study 1, subjects rated the degree to which each of 149 foods were dietary permissable or dietary forbidden. The number of avoided foods correlated positively with restraint score. Study 2 compared Herman and Mack's (1975) 1- and 2-milk shake preloads to two nonforbidden preloads of equivalent calories. Food type, and not perceived calories, was found to be the element of the preload required to cause disinhibition among restrained eaters, both within the experiment and outside the experimental setting. Study 3 examined the effects of anticipated consumption (varying food type and calories) on the restrained eating pattern. Only restrained eaters anticipating a forbidden food (whether high or low in calories) were disinhibited. The restrained literature was reconsidered in light of the forbidden food hypothesis. PMID- 2592676 TI - The skin-flushing response: autonomic, self-report, and conditioned responses to repeated administrations of alcohol in Asian men. AB - This study examined the skin-flushing response in Asian men, which is a low-risk factor for alcoholism. Asian men who did and did not flush to alcohol consumed 0.5 g/kg ethanol during three sessions with alcohol, and placebo in a fourth session. The results indicated that: (a) Asian men who flushed to alcohol showed pronounced cardiovascular changes that did not exhibit differential tolerance over 3 sessions, (b) there were surprisingly few self-reported mood differences in response to alcohol between those who did and did not flush, and (c) finger pulse amplitude decreased and self-ratings of "boastful" increased significantly in response to placebo challenge in those men who did not flush. These results raise questions about the psychological mechanisms by which the skin-flushing response inhibits the development and expression of alcoholism. PMID- 2592677 TI - Electrodermal nonresponding, premorbid adjustment, and symptomatology as predictors of long-term social functioning in schizophrenics. AB - The hypothesis that electrodermal nonresponsiveness to orienting stimuli delineates a core group of "Kraepelinian" type schizophrenics was tested by following up social functioning outcome over a 2-year period in 37 schizophrenics. Good social functioning outcome required both some self supporting ability in the job market and a minimal social life. The prior assessments included monitoring of electrodermal responses to a series of moderately intense tones, ratings of reported and observed symptoms during an interview, and ratings of premorbid adjustment on the basis of an interview with a close relative. Electrodermal nonresponding, poor premorbid adjustment, and negative symptomatology predicted poor social functioning during the second follow-up year, but the relationship to nonresponding pertained exclusively to a group of 15 first-episode patients. Discriminant analysis showed that electrodermal nonresponding and symptoms were the only independent predictors of outcome. PMID- 2592678 TI - Self-structure in schizophrenia. AB - This study used a set-theoretical model to construct self-perception structures and person-perception structures for 10 recently hospitalized schizophrenic patients, 10 nonschizophrenic patients recently hospitalized for depression, and 10 nonpsychiatric subjects. Overall self-perception structures were significantly less elaborated in the schizophrenic patients when compared with either the psychiatric or the nonpsychiatric comparison group. No comparable differences were found for measures taken from the person-perception structures. The degree of elaboration of self in the particular context of self as psychiatric patient was found to be correlated (r = .74, p less than .01) with Global Assessment Scale ratings of current functional level in the schizophrenic group. PMID- 2592679 TI - Hypnotic blindness, awareness, and attribution. AB - Examined whether performance on a spelling task would be influenced by visual information in the reported absence of hypnotized subjects' awareness of that information. Experiment 1 visually presented uncommon spellings of homophones to subjects before and during a suggestion for hypnotic blindness, and subsequently tested subjects' spelling of the homophones. Words presented during hypnotic blindness influenced subjects' spelling performance. Subjects' attributions of their performance did not involve awareness of the homophones. Experiment 2 used the nonexperiment methodology to examine the impact of demand characteristics and indicated that the performance attributions of subjects of Experiment 1 could not be explained in these terms. The discussion focuses on implicit perception in hypnotic blindness and on the relevance of attributions about behavioral performance on hypnotic phenomena. PMID- 2592680 TI - Observational conditioning of fear to fear-relevant versus fear-irrelevant stimuli in rhesus monkeys. AB - Two experiments examined whether superior observational conditioning of fear occurs in observer rhesus monkeys that watch model monkeys exhibit an intense fear of fear-relevant, as compared with fear-irrelevant, stimuli. In both experiments, videotapes of model monkeys behaving fearfully were spliced so that it appeared that the models were reacting fearfully either to fear-relevant stimuli (toy snakes or a toy crocodile), or to fear-irrelevant stimuli (flowers or a toy rabbit). Observer groups watched one of four kinds of videotapes for 12 sessions. Results indicated that observers acquired a fear of fear-relevant stimuli (toy snakes and toy crocodile), but not of fear-irrelevant stimuli (flowers and toy rabbit). Implications of the present results for the preparedness theory of phobias are discussed. PMID- 2592681 TI - Characterizing life events as risk factors for depression: the role of fateful loss events. AB - Empirical associations between life events and health are often weak, in part because event exposure measures may group together very different kinds of experiences within a single event category. Attempts to refine the measures (by using respondents' subjective appraisals of event stressfulness or by taking into consideration situational and personal factors that influence the contextual threat of the events) may strengthen the association, but they cloud the clarity of any causal inference by confounding the measure with extraneous variation. Instead, the use of descriptive information about what actually happened before, during, and after each event is recommended to define exposure to potent, fateful life events. In a comparison of 96 patients with major depression and 404 community residents with no apparent depression, the odds that a person would have experienced one or more events meeting criteria for fatefulness and disruptiveness was 2.5 times greater in the depressed group. PMID- 2592682 TI - Life stressors, social resources, coping, and the 4-year course of unipolar depression. AB - Little is known about the effects of psychosocial factors on the long-term course of unipolar depression. This article examines the 4-year stability and change in life stressors, social resources, and coping, and their effect on the course of treated unipolar depression among 352 men and women. Depressed patients were assessed at treatment intake and at 1-year and 4-year follow-ups. Over the 4 years, patients improved in symptom outcomes, the quality of social resources, and coping responses; there were some declines in life stressors. Life stressors, social resources, and coping were related to patient functioning concurrently, after controlling for demographics, initial treatment, and initial dysfunction severity. Preintake medical conditions and family conflict consistently predicted poorer long-term outcomes. The findings imply that medical conditions and family conflict are important risk factors that predict poorer long-term outcome of depression. PMID- 2592683 TI - Parental communication deviance and schizophrenia: a cross-cultural comparison of Mexican- and Anglo-Americans. AB - Levels of parental communication deviance (CD), as measured on the Thematic Apperception Test (TAT), were compared among families of schizophrenic patients in two culturally distinct groups. Spanish-speaking Mexican-American parents of schizophrenics completed the TAT in their native language, and CD was coded from their stories by a Spanish-speaking rater. Mexican-American parents had levels of CD that were nearly identical to those of a carefully matched sample of English speaking Anglo-American parents. Factor scores that measure distinct subtypes of CD also did not differ across groups. The data suggest that levels of CD, despite discriminating between parents of schizophrenics and nonschizophrenics, do not vary across different languages and cultures. PMID- 2592684 TI - Schema congruence and depression: loss of objectivity in self- and other inferences. AB - Depressed and nondepressed students judged the plausibility of positive and negative inferences ostensibly made either by themselves or by others. Negative self-inferences were judged by depressed students as more plausible, and positive other-inferences as less plausible. The results were in accord with Beck's (1967) theory of schema-based distortion in depression, which proposes that persons vulnerable to the development of depression are prone to make erroneous negative inferences and to then regard those inferences as plausible and correct. The results also suggested that depressed persons responded differentially depending on whether they were instructed to consider the inferences as their own or another's, whereas nondepressed persons did not. PMID- 2592685 TI - Effects of dietary restraint, obesity, and gender on holiday eating behavior and weight gain. AB - This investigation evaluated the impact of dietary restraint, relative weight, and gender on holiday eating behavior and weight gain. 65 Ss (31 men and 34 women) completed detailed food records for the 2 days before, the 4 days during, and the 2 days after the Thanksgiving weekend. Results indicated increased eating during the Thanksgiving holiday, with men eating more than women and the obese eating less than the nonobese. There was also a significant Total Restraint X Weight X Time interaction, with unrestrained normal-weight subjects behaving similarly to high-restrained overweight subjects over time. There was also a highly reliable Total Restraint X Sex X Time interaction. The most striking finding from this interaction was that high-restrained women displayed decreases in their dietary intake over time. Correlational analyses revealed that restraint scores were negatively associated with dietary intake over the 8-day period but were positively associated with weight gain. The implications for dieting, eating behavior, and energy balance are discussed. PMID- 2592686 TI - A comparison of the validity of three scales for the assessment of dietary restraint. AB - The construct validity of Herman and Polivy's Restraint Scale (RS), the restraint factor of the Three Factor Eating Questionnaire (TFEQ-R), and the restraint scale of the Dutch Eating Behavior Questionnaire (DEBQ-R) were investigated by relating these scales to self-reported mean caloric intake per day and to other measures associated with disordered eating and figure consciousness. A factor analysis showed that the three restraint scales measure different components of the restraint construct. A high score on the RS was closely related to consequences of mostly unsuccessful dieting, such as disinhibited eating and weight fluctuations, but not to successful overall caloric restriction in everyday life. High scores on the TFEQ-R and the DEBQ-R represented the more successful dieting behavior component of restraint. The three scales have in common a motivational component of restrained eating, including concerns about shape and weight, and desire for thinness. PMID- 2592687 TI - Autobiographical memory in a case of multiple personality disorder. AB - Previous research on multiple personality disorder (MPD) has been concerned with between-personalities amnesia, and little attention has been paid to within personality memory function. This study examined the autobiographical memory of a multiple personality patient, I.C., with cueing procedures that have proven useful in previous studies of normal and abnormal memory. Results indicated that I.C. was able to retrieve autobiographical episodes from the recent past, although her performance differed in several respects from that of matched controls. The study also revealed a striking deficit in I.C.'s autobiographical memory for childhood: She was unable to recall a single episode from prior to the age of 10 in response to various retrieval cues, whereas control subjects had no difficulty recalling numerous childhood episodes. This phenomenon of extended childhood amnesia has not been reported previously in studies of MPD. PMID- 2592689 TI - The ADA and dentistry answer a critical public health challenge. PMID- 2592688 TI - Patients' attitudes toward dentistry and AIDS. PMID- 2592690 TI - Educating and interacting with your patients. PMID- 2592691 TI - AIDS and dentistry: the governmental view. PMID- 2592692 TI - Kaposi's sarcoma in patients with AIDS. AB - All health care providers must become increasingly aware of the early signs and symptoms of AIDS as KS frequently appears in the head, neck, and oral regions. Dentists are responsible for recognizing these lesions, especially the early lesions, providing dental treatment as appropriate, and for referring patients with AIDS for counseling and treatment that cannot be provided in their office. Early detection of KS is particularly important for patients receiving dental treatment. The dentist must be careful not to further compromise the patient's health by extensive or stressful dental treatment and to prevent intraoperative or postoperative complications. Early supportive and palliative care will improve the patient's prognosis. Dental care will help HIV-infected patients and those with AIDS to avoid caries and periodontal disease. In addition, regular dental care will enable the dentist in the early diagnosis of the disease's oral manifestations, such as candidiasis, hairy leukoplakia, KS, or other oral opportunistic infection. Treatment of these conditions can significantly improve the patients' quality of life and their chances for survival. When universal precautions are used for infection control in the dental office there is no reason that comprehensive dental care cannot be provided for HIV infected patients--both for those that we know are infected and for those that are infected and we don't know about. PMID- 2592693 TI - Radiation therapy for the treatment of palatal Kaposi's sarcoma: report of case. PMID- 2592694 TI - AIDS therapy and the detection of adverse drug effects in dental practice. PMID- 2592695 TI - L-tryptophan. PMID- 2592696 TI - The impact of a quality assessment program on the practice behavior of general practitioners: a follow-up study. PMID- 2592697 TI - Retirement: perceptions of a professional couple. PMID- 2592698 TI - Clinical, radiographic, and histological manifestations of dentin dysplasia, type I: Report of case. AB - Dentin dysplasia, type I, is a rare dental anomaly characterized by abnormal dentin formation affecting the roots of both primary and permanent teeth. Short, conical roots with occlusion of the pulp chamber and canal are produced. Periapical radiolucent areas are common, although no evidence of caries or trauma to the tooth may be seen. Coronal mantle dentin is unaffected, resulting in an apparently normal clinical crown. An abnormality may not be suspected until radiographs reveal pulp and root changes. Orthodontic treatment can be a successful variation of the usual treatment offered to patients, and is discussed in this case report. PMID- 2592700 TI - White plaque of the dorsal tongue. AB - A case of oral lichen planus has been discussed. The causes, associated conditions, laboratory tests, and treatment were addressed. The use of cyanoacrylate "super glue" may have acted as a contactant and promoted the patient's localized lichenoid process. No additional treatment was provided other than confirmation of clinical suspicions. The most important factor was ruling out the possibility of a dysplastic or a malignant process. Should the patient become symptomatic, the treatment would probably start out with kaolin and pectin (Kaopectate) lidocaine/benadryl rinses. Should supportive therapy fail, alternative regimens including topical to systemic corticosteroids would be considered. PMID- 2592699 TI - An evaluation of different composite resin systems finished with various abrasives. PMID- 2592701 TI - Continuing education course listing for January to June 1990. Council on Dental Education. PMID- 2592702 TI - Nutrient intake recommendations needed for the older American. PMID- 2592703 TI - The 1980s: a look at a decade of growth in dietetics through the pages of the Journal. PMID- 2592704 TI - The 10th edition of the Recommended Dietary Allowances: what's new in the 1989 RDAs? PMID- 2592705 TI - Attitudes, knowledge, and problem-solving approach of Michigan dietitians about aging. AB - Dietitians' attitudes and knowledge about aging are important because of the potential influence on quality and quantity of nutrition services provided to older adults. Four instruments were used to survey active members of The American Dietetic Association (ADA) in Michigan. The survey was mailed to 1,408 dietitians; 738 responded (52.4%). The responding dietitians were predominantly under 40, well educated, and female, which was consistent with the 1986 national census of ADA members. The results indicated that dietitians hold positive attitudes toward older adults in most areas. An exception was that a majority of the dietitians perceived older adults as resistant to treatment. Although dietitians' knowledge about aging generally was adequate, the questionnaire revealed that dietitians lacked knowledge in the areas of economic and health status; dietitians answered that older adults have a lower income and are sicker and more institutionalized than is in fact true. These are critical areas of deficiency in knowledge by dietitians, since food and nutrition issues often involve money and health. In the problem-solving section of the study, the dietitians usually focused on one specific environment or area of concern. Neither the full range of all possible environments for older adults nor the diversity of older adults' needs was usually considered. Continuing education as well as comprehensive undergraduate courses on aging would have a positive influence on Michigan dietitians' attitudes and knowledge about aging. PMID- 2592706 TI - Factors that influence the elderly to use traditional or nontraditional nutrition information sources. AB - This study analyzed sociodemographic variables, access to medical care, health status-related variables, and nutrition status-related variables to determine their ability to predict an orientation toward traditional or nontraditional nutrition information sources among aged subjects in Eugene, OR. Data were collected from 165 randomly selected subjects by trained interviewers using face to-face interviews. Nutritionist orientation was measured by a Traditional/Nontraditional Index (TNT Index) developed for the study. Nutrition knowledge and misinformation, supplement use, and sources of nutrition information were also investigated. Predictors of nontraditional nutritionist orientation were acceptance of nutrition misinformation and male sex (adjusted R2 = .09). For women, predictors of a similar orientation were acceptance of nutrition misinformation, low knowledge of general nutrition information, and low functional health status (adjusted R2 = .19). Mean nutrition knowledge scores were high, with a mean of 4.7 (standard deviation [SD] = 0.8) on a scale ranging from 4 (high) to 8 (low). However, many of the subjects did not list dairy foods (28%) and grains (27%) as necessary in the diet. In addition, belief in certain nutrition myths was widespread. More than 58% were taking one or more supplements (mean = 1.4 supplements per day, SD = 1.98). Physicians were mentioned as most likely sources of nutrition information, with dietitians and health food store personnel mentioned second, indicating the importance of marketing efforts for registered dietitians. PMID- 2592707 TI - Dietary status of Seventh-Day Adventist vegetarian and non-vegetarian elderly women. AB - The purpose of this study was to investigate nutrient intakes of Seventh-Day Adventist elderly women who were similar in many demographic and life-style factors except for choice of diet. Twenty-three vegetarian and 14 non-vegetarian elderly women (mean +/- standard error ages 72.2 +/- 1.3 and 71.1 +/- 1.4 years, respectively) were recruited on the basis of several selection criteria, including race, religion, education, geographic area, Quetelet index, self reported absence of major chronic disease and use of medications, and physical activity. Average years +/- SE of adherence to dietary regimens were 47.0 +/- 2.9 and 71.2 +/- 1.4 in the vegetarian and non-vegetarian groups, respectively. Results from analysis of 7-day food records showed that vegetarians consumed significantly less cholesterol, saturated fatty acids, and caffeine but more carbohydrate, dietary fiber, magnesium, vitamins E and A, thiamin, pantothenic acid, copper, and manganese than non-vegetarians (p less than .05). On the basis of group means, 67% of the Recommended Dietary Allowance was met for all nutrients except zinc and vitamin D in both groups, and vitamins B-6, folacin, and vitamin E in the non-vegetarians. Compared with non-vegetarians, vegetarians had significantly lower serum glucose (5.18 +/- 0.11 vs. 4.65 +/- 0.09 mmol/L), low-density-lipoprotein cholesterol (4.08 +/- 0.25 vs. 3.34 +/- 0.19 mmol/L), and total cholesterol levels (6.46 +/- 0.27 vs. 5.62 +/- 0.21 mmol/L) (p less than .05). In summary, when healthy elderly vegetarian women were compared with closely matched non-vegetarian peers, the vegetarian diet was associated with improved nutrient intake and associated reductions in blood glucose and lipid levels. PMID- 2592708 TI - Hypophagia among hospitalized elderly. AB - A prospective study was done in 21 hospitalized medical patients to determine the effects of age and gender on food intake. From precise weighing of food served and uneaten, macronutrients and micronutrients ingested during the hospital stay were determined. Even though the hospital diet served was adequate in energy and protein, 38% of the patients ingested less than 65% of their nutritional requirements, with a higher percentage of those with inadequate intake among the elderly than among the young (28% vs. 10%). Patients over 65 years of age ingested less energy and protein than those under 65 years of age (1,167 vs. 1,967 kcal, p less than .01; 47 vs. 78 gm, p less than .05). The gender of the patients had no influence on food intake. More than 60% of the medical patients, especially the elderly, had an inadequate intake of micronutrients: folate, 100% of the elderly vs. 93% of the young; zinc, 90% vs. 64%; magnesium, 90% vs. 36%; and vitamin B-6, 90% vs. 64%. Multiple stepwise regression analysis showed that age and body weight on admission were of predictive value in terms of subsequent nutrient intakes during the hospitalization. Patients who were over 65 years old and weighted less than 80% of their ideal body weight consumed significantly less energy and fewer macronutrients and micronutrients. PMID- 2592709 TI - Evaluation of the offer vs. serve option within self-serve, choice menu lunch program at the elementary school level. AB - The feasibility of a centralized menu and the effectiveness of an "offer vs. serve" option within a self-serve, choice menu lunch program at the elementary school level were determined. Student trays (no. = 370/day) were visually evaluated for foods chosen and consumed. The same 1-week menu was served at two urban Southern schools. One represented a high-poverty-area, all-black-student school and the other represented a middle-income-area school with a white to black student ratio of 3:1. Students were able to choose the required USDA minimal number of three foods, and 66% of the foods selected were similar at the two schools, demonstrating that a centralized menu was feasible. Three-fourths of the students were able to choose more than 75% of one-third of the RDA for all nutrients except pyridoxine and ascorbic acid at both schools and iron at the high-poverty school. Twenty-five percent or more of the students did not consume 75% of one-third the Recommended Dietary Allowance for thiamin, vitamin B-6, ascorbic acid, iron, and magnesium at either school or of niacin and vitamin A at the middle-income school. Overall plate waste was 12.9%, with younger children wasting more food than older children and more waste in the middle-income than the high-poverty school. In general, the "offer vs. serve" was an effective option. PMID- 2592710 TI - A comparison of food frequency and diet recall methods in studies of nutrient intake of low-income pregnant women. AB - The aim of this study was to develop a self-administered food frequency questionnaire for use with low-income pregnant women and to evaluate its performance in classifying women according to nutrient intake. Index nutrients used were energy, protein, calcium, iron, zinc, and vitamins A, B-6, and C. Two hundred ninety-five Massachusetts women, aged 14 to 43 years, participated in the field test of the questionnaire. A subset of 95 women provided three 24-hour diet recalls for use in comparative studies. Correlation coefficients between questionnaire and diet recall scores were adjusted for measurement error resulting from the limited number of 24-hour recalls per subject, and their confidence intervals were computed. When subjects with implausibly high energy scores (greater than 4,500/day) were removed from the sample, reducing sample size by about 15%, correlation coefficients increased substantially (25% to 64%) for all nutrients except vitamin A. Adjusted correlation coefficients exceeded 0.5, excluding vitamin A (r approximately 0.15), and quintile comparisons indicated that the questionnaire would correctly identify a high proportion of the women having low intake of selected nutrients. We conclude that a self administered questionnaire can provide useful data about individual recent intake of selected nutrients in a majority of English-speaking, low-income pregnant women, but that overestimation of food use may occur among up to 20% of this population. PMID- 2592711 TI - Relationship of socioeconomic status and living arrangements to nutritional intake of the older person. AB - The number and proportion of older Americans have grown rapidly in recent years, and this trend is expected to continue. Adequate nutritional intake is essential for optimal physical and mental activity. The purpose of this study was to examine the relationship of socioeconomic status and living arrangements to nutritional intake of persons 55 years of age or older living in South Carolina. Data on 268 subjects who participated in the South Carolina Nutrition Survey, which was based on a true probability sample that represents the state's adult population, were analyzed. Eighty-nine percent of the subjects were found to have poor nutritional intake on the basis of a combination of four index nutrients: iron, vitamin B-6, calcium, and vitamin A. The data did not show a relationship between living arrangements and nutrient intake but affirmed the literature findings that support a positive relationship between low socioeconomic status and inadequate nutritional intake. PMID- 2592712 TI - Infection control in the long-term-care nursing facility. PMID- 2592713 TI - Calcium content of soup stocks with added vinegar. PMID- 2592714 TI - Health beliefs and supplement use: adults in seven western states. PMID- 2592715 TI - Position of the American Dietetic Association: optimal weight as a health promotion strategy. AB - The American Dietetic Association supports the concept of optimal weight that considers a variety of factors to determine the most favorable weight for the individual. Adequate research exists to support the following: The prevention of obesity in children and adults through nutrition and health education should be a primary objective for registered dietitians and other health care professionals. Optimal weight for individuals should be determined by considering health risks, heredity, age, sex, percentage body fat, and realistic goal-setting. Children should not be placed on restricted-calorie diets; rather, efforts should be made to encourage the child to be physically active, to eat a well-balanced diet, and to return to internal control of eating. Also, normalization of the feeding relationship between parent and child is important. Weight control programs should include behavioral management techniques for food intake, exercise, stress, and improved self-esteem. The programs should focus on loss of body fat and avoidance of repeated diet failures. Healthful behaviors that can prevent and reduce the incidence of obesity should be encouraged by registered dietitians and other health care providers, educators, the food industry, insurance companies, employers, school programs, and families. The concept of optimal weight may be modified as scientific evidence is accumulated on the determinants of body composition and weight, effective nutrition and health education approaches, and effective weight management strategies. Research is needed to permit development of more effective weight management strategies and programs for the overweight population. PMID- 2592716 TI - Supply and demand. PMID- 2592717 TI - Activities of coordinated dietetic program directors compared by educational background. AB - This study was designed to ascertain the activities performed by coordinated program directors, compare current activities with 5-year expectations, and identify differences in importance and time spent on 14 pertinent activities by directors with master's degrees and those with doctorates. Responses were collected by a descriptive survey of 64 directors, all of whom participated. Program directors with master's degrees considered public relations with affiliations, attending faculty meetings, student advisement, and reading professional materials significantly more important (p less than .05) than did directors with doctorates, who considered faculty evaluations and research significantly more important (p less than .01). Directors with doctorates spent significantly less time in teaching (p less than .05) than those with master's degrees. Responsibilities of directors in the 22 submitted descriptions were organized into five categories: program management, curricular affairs, policies impacting on programs, student advisement and counseling, and academic activities. In the ADA Standards of Education, responsibilities of directors include program assessment, planning, and evaluation; in this study, those responsibilities were placed in the program management category. Exhibition of leadership qualities, revision of curriculum, and counseling and recruitment of students were responsibilities most frequently included in the position descriptions; however, those responsibilities were in categories other than program management. The responsibilities could serve as a guide for the development of a position description and as criteria for the role of a coordinated program director. PMID- 2592718 TI - Functional status and cognitive impairment in Alzheimer's patients with and without depression. AB - Cognitive impairment and depression each compromise functional status in the elderly, but it is not known whether their coexistence is associated with additive functional impairment. The effect of the presence or absence of a diagnosis of major depression on functional status was examined in a group of 50 community-residing patients with dementia of the Alzheimer's type (DAT). Patients were diagnosed as depressed (N = 20) or not (N = 30) according to DSM-III criteria. Cognitive status was assessed with the Mini-Mental State Exam (MMSE), and functional status was assessed by family report of Instrumental Activities of Daily Living (IADLs). Consistent with previous reports, patients with a depression diagnosis were less cognitively impaired than their nondepressed counterparts. When cognitive status was controlled for, depression diagnosis was found to have a main effect on functional impairment. Although the direction of effects between depression and functional limitations was not determined here, these results suggest that alleviating depression may decrease functional limitations in DAT patients. PMID- 2592719 TI - Physical restraints and agitation in nursing home residents. AB - An observational study was performed to determine whether the use of physical restraints in agitated nursing home residents leads to decreased or increased agitation. Results indicate that restraint use does not decrease agitation in nursing home residents. Residents exhibited either the same amount or more agitated behaviors when they were restrained than when they were not restrained, suggesting that the act of restraining may itself contribute to manifestations of agitation. The implications of the use of restraints in agitated nursing home residents are discussed, with particular reference to the prevention of falls. PMID- 2592720 TI - A longitudinal study of impaired glucose tolerance and diabetes mellitus in the aged. AB - This longitudinal study of glucose tolerance in the residents of a Jewish home for the aged (JHA) is now in its 25th year. Of 1,177 supposedly nondiabetic persons screened on admission from 1965 to 1986, 22.5% had impaired glucose tolerance (IGT), reflecting its undiagnosed prevalence among the Jewish elderly in the community. The incidence of IGT was lower in 1969-1973, when the average age on admission was 77 years, than in 1982-1986, when the average age was 83.5 years. However, aging was not the only factor affecting glucose tolerance (GT). The rise in the residents' age in the last 10 years was not accompanied by an increased rate of deterioration of GT in the annual screenings of 1970-1984, suggesting that there was a delay in the effect of age on IGT and diabetes mellitus (DM). This was attributed mainly to the multimodal antidiabetic regimen (ADR) prevailing in the JHA in those years. Relaxation of this regimen was associated with a marked increase in the incidence of IGT and DM in the screenings of 1985-1987. When 25 newly diagnosed diabetics were put on a diabetic diet, 60% had normal or improved glucose tolerance tests (GTT) one to five years later. By contrast, in over half of the 80 residents whose first GTT did not indicate diabetes and whose diet was not as strictly controlled, the repeat GTT showed deterioration and was diabetic in 31%. CONCLUSIONS: Screening led to early diagnosis and institution of antidiabetic measures, probably avoiding or postponing the need for antidiabetic medication with its risk of iatrogenic hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592721 TI - An in vitro analogue of immune dysfunction with altered immunoglobulin production in the aged. AB - The consequences of aging of the immune system include impaired T-lymphocyte responsiveness and aberrant immunoglobulin production. Although T cells from elderly individuals have a well-described defect in lymphoblastic transformation in response to some polyclonal mitogens, immunoglobulin abnormalities have lacked a clear in vitro model. Peripheral blood mononuclear cells from 13 young and 13 old healthy donors were cultured with phytohemagglutinin (PHA) or pokeweed mitogen (PWM). Old-donor-cell phytohemagglutinin (PHA), but not PWM, cultures had significantly lower lymphoblastic transformation compared with young donor cultures. IgG, IgA, and IgM production tended to be lower in old- versus young donor PWM cell cultures. By contrast, despite lower lymphoblastic transformation in old-donor PHA cell cultures, immunoglobulin production was higher for old- versus young-donor cell cultures. No significant age differences were present in initial lymphocyte counts, percent B cells, T cells or monocytes, or helper/suppressor ratios to explain this enhancement in immunoglobulin production. PHA-stimulated mononuclear cell cultures in the aged demonstrate not only a defect in proliferation but also increased immunoglobulin production. This in vitro system may be useful to characterize further the pathogenesis of altered immunoglobulin production in the elderly. PMID- 2592722 TI - Increasing influenza vaccination adherence through voice mail. AB - The number of influenza and influenza-related deaths is alarmingly high, yet mean vaccination adherence rates among the high-risk elderly population remain at only 20%. The present study investigates the use of an inexpensive voice-mail system, TeleMinder, as a method of increasing influenza vaccination adherence among a subpopulation of elders identified as low adherers. The first group of older people received no intervention. Group 2 received a voice-mail message informing them of the cost, time, date, and location of an influenza vaccination clinic. Group 3 was exposed to posted and verbal announcements alone. Group 4 both received voice mail and was exposed to posted and verbal announcements. Vaccination adherence levels for groups 1 through 4 were 1.5%, 11.8%, 7.4%, and 37.5%, respectively. Voice mail significantly increased vaccination adherence either alone or in combination with posted and verbal announcements. These findings suggest that voice mail provides an inexpensive means of increasing influenza vaccination rates. PMID- 2592723 TI - Pancytopenia as the presenting manifestation of HIV infection in the elderly. PMID- 2592724 TI - Nonmedical complications of diagnostic workup for dementia [clinic conference]. AB - Testing for patients presenting with dementias can lead to diagnosis of disorders that can contribute to cognitive dysfunction, and to improvement, stabilization, or slowed deterioration in some demented patients. However, possible benefits must be balanced against possible costs. The present recommendations for workup of patients with dementia includes some tests with only marginal benefits, and a more limited workup may be as effective. This case demonstrates how important it is to be sensitive as well to possible effects on family relationships of demented patients. When we evaluate and treat demented patients, the dependence of the demented patient on the caregiver and the emotional and physical stresses experienced by many caregivers make it important to consider the patient and caregiver as a system vulnerable to many potential risks. PMID- 2592725 TI - The first certifying examination in geriatric medicine. AB - On April 22, 1988, the first Certifying Examination in Geriatric Medicine was administered jointly by the American Board of Internal Medicine and the American Board of Family Practice to 4,282 diplomates (ABIM = 2,202; ABFP = 2,080). This paper addresses both an analysis of the examination and the relationship between performance on that examination and a group of characteristics of the examinees, collected as part of the registration process. The pass rate was 56%. Performance on the examination was positively correlated with scores on the general certifying examinations and with training in geriatric medicine. Data provided by the candidates in an addendum to the application were also available for analysis and were used to derive correlations with groups of questions. The performance of candidates was positively correlated with seeing large numbers of elderly in hospitals, nursing homes, or home settings, working in a University Hospital, teaching and research, and the size of the community in which the candidate practiced. Physicians from long-term care settings did exceptionally well. Working in a solo practice setting was negatively correlated with performance on the examination as was working in a for-profit setting. PMID- 2592726 TI - Recognition of alcohol dependence in the elderly. PMID- 2592727 TI - Don't forget AIDS at any age. PMID- 2592728 TI - A versatile mercury vapour generating system suitable for long-term inhalation experiments. AB - A mercury vapour generating system is described that is based on the reduction of HgCl2 by SnCl2 in the input airstream of the inhalation chamber. The solutions of the two chemicals are pumped by peristaltic pumps from reservoirs through a miniature mixing chamber into the upper part of a sloping glass tube (reduction chamber) through which air is sucked into the inhalation assembly. The liquid flows down the slope and through a port into a Quickfit flask. Reservoirs can be filled and the collecting flask emptied without interruption of exposure. The desired vapour concentration is achieved by varying the rate of mercury injection and the rate of airflow. Concentration in the inhalation chamber can be measured by passing air through a mercury vapour monitor or by radioactivity when 203HgCl2 is used and a known volume of air is passed through a hopcalite absorber. Operation instructions and an experimental example with mice are given. PMID- 2592729 TI - Nasal irritation and pulmonary toxicity of aliphatic amines in mice. AB - The expiratory bradypnoea indicative of upper airway irritation in mice was evaluated during a 15-min oronasal exposure to increasing concentrations of twenty aliphatic amines. The airborne concentration resulting in a 50% decrease in the respiratory rate of mice (RD50) was calculated for each test compound. Moreover, eight out of the twenty amines were tested for pulmonary toxicity in mice and for the effects of a 120-min exposure on the respiratory rates of non anaesthetized, tracheally cannulated mice (RD50TC). Both allylamine and diallylamine showed RD50 values of 9 ppm and 4 ppm, respectively, while the RD50 values associated with exposure to saturated amines ranged from 50 to 200 ppm. Among the eight amines tested for both upper airway irritation and pulmonary toxicity, diisopropylamine and di-n-butylamine showed a RD50TC/RD50 ratio of less than 1, indicating that the respiratory toxicity induced by these two amines would be related primarily to pulmonary effects. On the basis of prior predictions proposed for upper airway irritants, tentative standards are given for ten amines. Moreover, it is suggested that the basis of standards for industrial exposure to diisopropylamine and di-n-butylamine should be specified. PMID- 2592730 TI - Transient renal impairment in rats after oral exposure to diethylene glycol. AB - Volume, specific gravity, creatinine, lactate dehydrogenase (LDH), leucine aminopeptidase (LAP), beta-galactosidase (GAL), leucocytes, erythrocytes, nitrite, protein (albumin), glucose, ketone, urobilinogen, bilirubin and pH were estimated in urine of rats after single (by gavage) or repeated (via drinking water) oral administration of diethylene glycol (DEG). Following single or repetitive doses (daily over 90 days) of 0.2 g DEG kg-1 body weight, no change in renal function was observed (no effect level). In urine of rats treated once with 0.7 g DEG kg-1 body weight, LDH activity was significantly enhanced one day after treatment. A single dose of 2.0 g DEG kg-1 body weight resulted in an additional rise in urinary GAL activity two days after treatment, a significant rise of urinary volume and a decrease in creatinine concentration and pH on the first day. One day following a single dose of 8.0 g DEG kg-1 body weight, in addition to the changes mentioned before, LAP activity was significantly elevated and the specific gravity decreased. However, in all experiments the wet weight of the kidneys remained normal as compared to controls. The results thus show dose dependent changes in several renal parameters, indicating a slight-to-moderate and reversible renal impairment. PMID- 2592731 TI - Carboxyhemoglobin in the rat: improvements in the spectrophotometric measurement and comparison to other studies. AB - An improved and simplified spectrophotometric method for the determination of carboxyhemoglobin (COHb) is described, which employs an equation to correct for the dissociation error during analysis. Two microliters, or less, of blood is diluted with an ammonium hydroxide solution directly in the measuring cuvette. A layer of light mineral oil overlying the diluent was found to increase measured COHb saturation of blood equilibrated with 100% CO. Sodium dithionite treatment of the oil further increased this value in one case. The measured COHb was shown to be affected directly by factors that alter hemoglobin concentration in the diluent (i.e. blood volume, hematocrit). Blood samples kept cold and under oil may be stored safely for as long as 10 days. Measurement of COHb by this method in rats exposed to 525, 900, 1800 and 2400 ppm CO produces higher values than those obtained with the 1965 spectrophotometric method of Commins and Lawther. Variations on the method of Commins and Lawther, as well as COHb values available in the literature for animals exposed to CO, are reviewed briefly. PMID- 2592732 TI - Predicting toxicokinetic parameters in humans from toxicokinetic data acquired from three small mammalian species. AB - Values for the independent kinetic variables, clearance (CL) and volume of distribution (V), for six xenobiotics--antipyrine, ethosuximide, phencyclidine, theophylline, valproic acid and warfarin--were culled from the literature for each of three small subhuman species and for humans, and then allometrically scaled. Scaling was performed in two ways. First, using kinetic data acquired for three small subhuman species and for man, scaled parameters were observed for goodness of fit to a standard allometric expression. Second, scaled parameters were averaged for three subhuman species. Mean scaled kinetic parameters from only three species were used to predict half-life values of the xenobiotics in humans. Finally, predicted percentages of the xenobiotic burdens remaining in humans at the end of four allometrically-predicted half-lives were compared with the expected percentages of remaining xenobiotic based upon four actual half lives in humans. The results suggest that it may be feasible to estimate, using three small subhuman species, allometrically-derived toxicokinetic parameters of some substances in man with sufficient accuracy to be of practical value. PMID- 2592733 TI - A comparison of the effects of dietary cadmium on heart and kidney antioxidant enzymes: evidence for the greater vulnerability of the heart to cadmium toxicity. AB - This study demonstrates the greater susceptibility of the heart as compared to the kidney to cadmium in the presence of high dietary selenium. Male weanling rats were fed an adequate-copper low-selenium feed supplemented with 0, 10 or 50 ppm copper with or without 50 ppm dietary cadmium for 7 weeks. All rats received 0.5 ppm selenium in their drinking water. Cadmium treatment resulted in histopathological lesions in the heart, but not in the kidney. Although cadmium treatment resulted in more extensive effects on glutathione peroxidase and superoxide dismutase in the heart as compared to the kidney, no increase in peroxidation was noted in either organ, suggesting that cadmium cardiotoxicity can be dissociated from tissue peroxidation. Mean cadmium concentrations in the heart ranged from 0.55 to 1.22 micrograms cadmium g-1 tissue, wet weight, and in the kidney from 11.53 to 21.04 micrograms cadmium g-1 tissue, wet weight. In both tissues examined, cadmium levels were influenced by dietary copper and heart cadmium concentrations did not correlate with either the biochemical or histological lesions observed. Thus, tissue cadmium levels alone may not be adequate for predicting cadmium toxicity. PMID- 2592734 TI - Dose and time effects of combined exposure to lead and ethanol on lead body burden and some neuronal, hepatic and haematopoietic biochemical indices in the rat. AB - Ethanol (1, 2 or 5 g kg-1) and lead (0.55 g l-1 in drinking water) were given either alone or in combination for 4 months to rats. The uptake of lead in tissues, some lead-sensitive variables, the levels of biogenic amines in different brain regions, hepatic lipid peroxidation, glycogen and blood glucose concentrations were measured. Ethanol or lead when given alone inhibited the activity of blood delta-aminolevulinic acid dehydratase (ALAD). The co administration of 5 g kg-1 but not 1 or 2 g kg-1 ethanol significantly enhanced the lead-induced inhibition of blood delta-ALAD activity and the elevation of delta-aminolevulinic acid (ALA) excretion. Co-exposure to lead and ethanol (5 g kg-1) produced a more pronounced increase in hepatic lipid peroxidation and blood glucose level than either ethanol or lead alone. This combination also caused a significant increase in the dopamine (DA) contents of striatum, midbrain and pons medulla, norepinephrine (NE) contents in midbrain and 5-hydroxytryptamine (5-HT) contents of hypothalamus, striatum, midbrain and pons medulla over levels produced by lead alone. However, the level of NE in hypothalamus decreased upon co-administration. The uptake and retention of lead was significantly higher in blood, liver, kidney and brain in animals co-exposed to lead and 5 g kg-1 ethanol. Blood and kidney lead was also increased by 2 g kg-1 ethanol. The results suggest that prolonged and heavy consumption of alcohol may increase the toxicity of lead. PMID- 2592735 TI - Lipid peroxidation in acrylonitrile-treated rats, evidenced by elevated ethane production. AB - The intraperitoneal administration of acrylonitrile (greater than 25 mg kg-1) to rats is associated with an increased production of ethane and a rise of the serum activity of the cytosolic enzyme, sorbitol dehydrogenase. These effects are prevented by pretreatment with vitamin E and the microsomal enzyme inhibitor SKF 525A, but are exacerbated by pretreatment with the microsomal enzyme inducer, phenobarbital. Repeated intraperitoneal administration of acrylonitrile (40 mg kg 1) for four weeks also increases ethane production and serum SDH activity, and produces various morphological changes in liver parenchymal cells (necrosis, increased mitotic activity, increased nucleolar size and myelinic figures in mitochondria) and inhibits the growth of the animals. All these effects are prevented by the administration of vitamin E (190 mg kg-1 i.p., daily) during the last two weeks of treatment. A dose of sodium cyanide (2.5 mg kg-1 i.p.) which leads to a urinary excretion of thiocyanate similar to that found after the intraperitoneal administration of 25 mg kg-1 acrylonitrile, does not stimulate ethane production. This study suggests that the hepatoxicity of acrylonitrile may, at least partly, result from a lipoperoxidation process and is linked with its microsomal oxidative biotransformation. PMID- 2592736 TI - Mycotoxins, pesticides and the immune system. PMID- 2592737 TI - Evaluation of metabolic status in amiodarone-induced thyroid disorders: plasma coenzyme Q10 determination. AB - In previous works we have demonstrated that Coenzyme Q10 (CoQ10) levels have a significant inverse correlation with thyroid hormone concentration in patients with spontaneous hyper- or hypothyroidism. In order to verify whether this correlation is maintained in patients on long-term amiodarone therapy, in whom thyroid metabolism is altered by the iodine contained in the drug, we have studied 30 patients with thyroid dysfunction induced by chronic amiodarone treatment. We have distinguished four groups of patients: group A (n = 8): patients with true hyperthyroidism induced by drug administration; group B (n = 11): patients with mild hyperthyroid symptoms, but isolated thyroxine increase or dissociation between different indexes of thyroid function; group C (n = 5): patients with normal thyroid hormone levels, but increased TSH levels; group D (n = 6): patients who appeared really clinically euthyroid, with normal thyroid hormone levels and normal TSH response to TRH. In group A patients, plasma CoQ10 levels averaged 0.49 +/- 0.03 micrograms/ml, significantly lower than those in normal subjects and similar to those observed in spontaneous hyperthyroid patients. In group B patients, CoQ10 levels were in the normal range (0.88 +/- 0.10 microgram/ml). In group C patients, CoQ10 levels were lower than those in normal subjects and similar to those of group A patients (0.49 +/- 0.04 microgram/ml); they differed, in regards to CoQ10 values, in comparison with spontaneous primary hypothyroid patients, who had very high levels of plasma CoQ10. Finally, in group D patients, CoQ10 levels were in the normal range (0.77 +/- 0.04 microgram/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592738 TI - Direct tubular effect on calcium retention by hydrochlorothiazide. AB - Previous studies with hydrochlorothiazide revealed a calcium retaining effect of this substance. The mechanism by what this is done is still matter of controverse discussion. Effects of hydrochlorothiazide on vitamin D metabolism have been reported as well as those on parathyroid function. To further clarify the calcium retaining potency of hydrochlorothiazide (HCTZ) we treated 10 healthy young volunteers for four weeks with 2 x 50 mg HCTZ. In all volunteers we observed a marked decrease in urinary calcium excretion as well as in calcium clearance. Furthermore, we found a slight rise in ionized serum calcium (6.7%) and in intact PTH, as well as a 36% drop in 1,25-(OH)2-D3-levels. These effects were reversible after discontinuation of the treatment. No change was observed in urinary cAMP, phosphate excretion, serum anorganic phosphate levels, serum calcitonin and magnesium levels. Data presented here suggest that treatment with HCTZ causes a persistent reduction in calcium excretion through direct tubular effects, inhibits hydroxylation of vitamin D, and does not affect parathyroid function. PMID- 2592739 TI - Clinical value of the measurement of bone remodelling markers in primary hyperparathyroidism. AB - This study was performed in order to evaluate the clinical usefulness of the measurement of total serum alkaline phosphatase activity (AP), serum osteocalcin (BGP) and urinary hydroxyproline (OHPr) in assessing bone remodelling in primary hyperparathyroidism. Thirty-two patients with primary hyperparathyroidism were included in the study. No statistically significant differences were observed between the mean values of Z-scores obtained for each marker. Furthermore, an inverse correlation was found between percentage of bone mineral content at the distal radius and both BGP (r = -0.57; p less than 0.05) and AP (r = -0.49; p less than 0.05). The results obtained demonstrate that, contrary to other metabolic bone diseases (e.g. Paget's disease of bone), all three markers examined may be used in clinical practice to evaluate the entity of skeletal turnover in primary hyperparathyroidism. PMID- 2592740 TI - Does SMS 201-995 normalize growth hormone secretion in acromegaly? GH day profiles and GH concentrations after oral glucose loading. AB - GH secretion in acromegaly was studied in 8 patients before and during treatment with SMS 201-995, a somatostatin analogue, 100 micrograms twice daily, by evaluating GH day profiles and GH suppressibility after oral glucose tolerance tests (OGTT). Normalization of GH secretion, estimated by OGTT, was only observed in the three patients who had a decrease in plasma GH to less than 2 micrograms/l after SMS 201-995 injection, and who had the lowest mean plasma GH levels during the day and the largest percent decline of mean plasma GH levels. We conclude that real normalization of GH secretion during SMS 201-995 therapy only occurs in a subset of patients. The data illustrate that the applicability of the generally held cut-off value of 5 micrograms/l, between normal and abnormal plasma GH, has to be reconsidered in the case of chronic intermittent subcutaneous therapy with SMS 201-995. PMID- 2592742 TI - Thyroid and steroid receptors. AB - Estradiol and progesterone receptor proteins (ER, PgR) have been demonstrated in neoplastic and non-neoplastic human thyroid. The aim of this study was to determine the sexual steroid receptor content of pathological non-malignant thyroid (solitary adenoma, simple nontoxic goiter), and the adjacent normal tissue of the thyroid. The results show the presence of ER and PgR (cytosolic and/or nuclear) in most of examined tissues both pathological and normal. Low levels of steroid receptors are found in the cytosol fraction, whereas the receptor content is higher in the nuclear fraction. No correlation could be found between receptor levels and patients' age, menstrual state in females, and sexual steroid circulating hormones. A significant difference has been observed between adenomas and simple goiters (p less than 0.001) in the nuclear ER, and between normal tissue surrounding adenoma and normal tissue in goiters (p less than 0.05). This result suggests that estradiol and progesterone receptors are present in thyroid tissue and may have a physiological function. PMID- 2592741 TI - The inhibitory effect of large doses of methimazole on iodine induced lymphocytic thyroiditis and serum anti-thyroglobulin antibody titers in BB/Wor rats. AB - The BB/Wor rat spontaneously develops autoimmune insulin dependent diabetes mellitus and lymphocytic thyroiditis (LT). Excess iodine ingestion enhances and low iodine diet decreases the incidence of LT in this rat model but does not affect the incidence of diabetes mellitus. The administration of a low dose of methimazole (MMI; 870 ng/gm bw ip daily) from 30-90 days of age had no significant effect on thyroid function or on the incidence of iodine induced LT and serum anti-thyroglobulin (Tg) antibodies measured by an ELISA assay. A large dose of MMI (0.05% in the drinking water) induced goiter and hypothyroidism. In addition, the incidence of LT was markedly attenuated (76% vs 6%, p less than 0.001) and reduced titers of serum anti-Tg antibodies (0.59 +/- 0.1 OD vs 0.08 +/ 0.01, p less than 0.001) were observed. This inhibitory effect of MMI on the occurrence of iodine induced LT in the BB/Wor rat may be due to the lower antigenicity of the poorly iodinated Tg secondary to MMI therapy and/or to an immunosuppressant effect of MMI itself. PMID- 2592744 TI - Quality assurance--guaranteeing a high level of care. AB - The quality assurance process in long-term care focuses on solving resident care problems and monitoring compliance with established standards of practice. An effective quality assurance monitoring system for long-term care includes the audit design steps of study design, criteria development, data retrieval, data interpretation, and definitive action. To assure that a clinical change in nursing practice results from quality assurance audit findings, it is imperative that organizational systems and structures be designed to disseminate these findings and follow through with identified courses of action. A formalized link between the quality assurance committee and nursing administration establishes the legitimate authority and accountability for follow-through to successfully integrate findings into actual practice. PMID- 2592743 TI - Severe hyperthyroidism due to neoplastic TSH hypersecretion in an old man. AB - A case is reported of neoplastic TSH hypersecretion in a 62-year-old man with severe hyperthyroidism and cardiovascular disease. He had been known to be hyperthyroid for 14 yr, and had been treated by thyreostatic drugs and subtotal thyroidectomy without satisfactory results. When he was referred to our Center, he was frankly hyperthyroid with both TSH (14 microU/ml) and thyroid hormone serum levels (TT4 24 micrograms/dl, TT3 370 ng/dl, FT41 7.9) above the normal range. alpha-subunit serum level was markedly increased (7.2 ng/ml), while beta subunit was only 0.3 ng/ml. Skull X-ray showed an enlarged sella turcica with destruction of the dorsum and an intrasellar tumor was visualized on conventional and computer tomography. TSH response was absent after TRH and domperidone, while TSH serum levels decreased by 25% after bromocriptine. Methimazole therapy temporarily decreased serum thyroid hormones to normal levels, while TSH levels rose to 34 microU/ml, thus indicating that pituitary-thyroid feed-back was maintained at a higher set point. Surgical attempt failed because of cardiac problems during anesthesia. Radiotherapy plus methimazole was begun and TSH serum levels first increased markedly, up to 140 microU/ml, and then progressively decreased without reaching normal values. After methimazole withdrawal hyperthyroidism recurred. PMID- 2592745 TI - Continuing education--adapting strategies to teach the elderly. AB - The elderly have special learning needs. Teaching programs for the elderly need to be adjusted for normal aging changes. Increased learning will occur if adaptation for aging changes are made. PMID- 2592746 TI - Give me a break--benefits of a caregiver support service. AB - Caregivers of elderly adults experience problems with self-image, stress levels, and the patient-relative relationship. Caregivers often receive relief only when the elderly adult is hospitalized. This study found a reduction in anxiety and suspicious behavior in caregivers, but helplessness was not reduced. Regular psychological evaluation may provide warning signs of the need for a period of relief for the caregiver. Further research is needed to determine which specific behaviors result in high stress for caregivers. PMID- 2592747 TI - Assess not assume--measuring the morale of cognitively impaired elderly. AB - The morale of cognitively impaired elderly has not been systematically studied as this group has been excluded in most studies of well-being. This study showed that most cognitively impaired persons who retain verbal skills were able to respond to a verbally administered assessment using the Philadelphia Geriatric Center Morale Scale. Support for the reliability and validity of measurement of morale in cognitively impaired elderly using the Philadelphia Geriatric Center Morale Scale was reported. Ratings of the morale of cognitively impaired persons by family members were significantly associated with self-report by elders, but tended to be lower. PMID- 2592749 TI - Relationship between respiratory pauses and heart rate during sleep in normal premature and full-term newborns. AB - To investigate the relationship between central respiratory pauses and heart rate, we performed polygraphic recordings in 23 normal newborns (35 to 41 weeks conceptional age). We monitored the electroencephalogram, rapid eye movements, movements of the upper and lower limbs, chin and diaphragmatic electromyogram, electrocardiogram, thoracic and abdominal respiratory movements, air flow and transcutaneous PO2. Heart rate changes were analysed by computer measurement of R R intervals and by cardiotachography. Respiratory pauses occurring after body movements and those not preceded by movements were studied separately. We analysed 1128 respiratory pauses greater than 3 s duration. No respiratory pause lasted more than 12 s. Independently of age, sleep state and respiratory pause duration, heart rate was significantly lower at the onset of respiratory pause, compared to control periods (selected away from the pause: 10 s before its onset and 20 s after its end). Heart rate slowed still further through the respiratory pause and reverted toward the baseline level after its end. When no movements preceded the respiratory pause, heart rate just before the pause was lower compared to control periods. These findings suggest the existence of simultaneous central commands responsible for both respiratory pause and heart rate deceleration. PMID- 2592748 TI - Sounds of silence--coping with hearing loss and loneliness. AB - The vast majority of people will suffer presbycusis during the aging process. This hearing loss has potential social consequences, which place these individuals at risk for loneliness. Nurses need to encourage thorough audiological examination and follow through on recommendations to improve hearing. The use of hearing aids needs to be encouraged. A suggested model of interaction among variables influencing loneliness identifies areas amenable to nursing intervention. Frequency of significant interaction and motivation to engage in interactions represent two important variables that influence loneliness. PMID- 2592750 TI - Plasma catecholamine concentrations of newborn piglets in thermoneutral and cold environments. AB - Plasma epinephrine and norepinephrine concentrations were measured in seventeen unanaesthetized 3 to 4 days-old piglets while in a thermoneutral environment (31.3 degrees C) and 30, 45 and 60 min after induction of environmental cold stress (19.9-23.1 degrees C). Plasma epinephrine and norepinephrine concentrations in a warm environment were 142 +/- 26 pg/ml, and 456 +/- 44 pg/ml respectively. Environmental cold stress evoked significant increases in norepinephrine values after 30 (624 +/- 58 pg/ml), 45 (626 +/- 60 pg/ml) and 60 (626 +/- 54 pg/ml) min of cold stress. Plasma epinephrine concentrations did not significantly change during environmental cold stress. Post-hoc stratification of piglets into normothermic (deep rectal temperature 38.6 degrees C-38.8 degrees C, n = 9) and hypothermic (deep rectal temperature 37.1 degrees C-37.7 degrees C, n = 7) subgroups revealed significant increases in plasma norepinephrine concentrations only in the hypothermic subgroup. We conclude that plasma norepinephrine, but not epinephrine, is increased in newborn piglets during environmental cold stress and that the changes in norepinephrine concentrations are related to body core hypothermia. We speculate that hypothermia-mediated reductions in peripheral norepinephrine breakdown and re-uptake contribute to the rise in circulating levels. PMID- 2592751 TI - Development of daily variations in methionine enkephalin within rabbit brainstem regions. AB - To examine the development of daily variations in methionine enkephalin, we measured methionine enkephalin concentration within five distinct brainstem regions in 3-day-old, 21-day-old, and adult rabbits at 09.30, 15.30, 21.30 and 03.30 h. Methionine enkephalin was measured by radioimmunoassay and methionine enkephalin concentration was expressed relative to wet tissue weight. In addition to defining the presence of a daily variation in methionine enkephalin concentration in the whole brainstem, we were interested in identifying brainstem region specific differences in this daily variation. Our data suggest that daily variations for methionine enkephalin are established by three days of life. Analysis of gross brainstem daily variation data suggests a nocturnal peak in methionine enkephalin concentration for 3-day-old animals in contrast to a diurnal peak for 21-day-old animals. Adult animals, showed a biphasic pattern. These gross daily variations reflect the net sum of distinct region specific patterns in methionine enkephalin concentration. Analysis by region reflects a region specific ontogeny in the development of daily variations for methionine enkephalin. Our data also suggest a caudal-rostral progression in the establishment of daily rhythms. Methionine enkephalin is involved in nociception and cardiorespiratory regulation. The observed developmental patterns may relate to the maturation and integration of these physiologic processes. PMID- 2592752 TI - Development of the response to adenosine during organ culture of young embryonic chick hearts. AB - Young (3 days-old) embryonic chick hearts (i.e., prior to innervation) show little electrophysiological response to adenosine. However, during embryonic development the sensitivity to adenosine greatly increases. In the present experiments, in which the chick hearts were placed into organ culture, the sensitivity to adenosine was found to increase with time in culture. Thus, the ability of adenosine to slow the spontaneous heart rate became greater during the course of organ culture. These results suggest that physiological responses to adenosine continue to develop in organ culture, and that the increased sensitivity to adenosine seen in ovo may be independent from the development of sympathetic or parasympathetic innervation. PMID- 2592753 TI - Placental outer and inner ring monodeiodination of thyroxine and triiodothyronines in the rabbit. AB - Both inner- and outer-ring iodothyronines deiodinating activity was found in homogenates of rabbit placentas. The T4 to rT3 and T3 to 3,3'-T2 deiodinating activity was already high on day 10 before delivery but decreased being about 7 times lowered on day 5. Once the T3 to 3,3'-T2 monodeiodination reached a low and a relatively steady level, the outer ring deiodination of T4 begun, reaching a peak value at about day 3 before term and then fell again. The fetal serum thyroid hormones levels were low, showing no significant variability during the period of observation. The results suggested that in the rabbit, representing animals in which the thyroid gland activity begins early in fetal life, there are two distinct phases of the placental monodeiodinating activity. The first is characterized by a high inner-ring deiodinating activity (yielding rT3) and is followed by the second phase with a high outer-ring deiodinating activity (yielding T3) declining just before term. PMID- 2592754 TI - Glycogenolytic responsiveness to glucagon, epinephrine, vasopressin and angiotensin II in the liver of developing hypothyroid rats. A comparative study of in vitro hormonal binding and in vivo biological response. AB - Both dose-response curves and time-courses of plasma glucose levels after single maximal doses showed that in vivo glycogenolytic responsiveness to glucagon and epinephrine was significantly higher in developing hypothyroid rats, whereas it remained unchanged after vasopressin and angiotensin II injections. In contrast with the decreased basal activity of phosphorylase(a), the glucagon-stimulated activity increased in hypothyroid rats, whereas it was only slightly modified under vasopressin stimulation. Daily thyroxine treatment abolished these abnormalities. Thus, there is a close correlation between glucose output and enzyme activation. The maximal binding capacity of [3H]vasopressin and [125I]glucagon was significantly decreased in hypothyroid rats, without changes in the apparent dissociation constant of hormone from its specific receptor. Daily thyroxine treatment also abolished this deficit, which moreover appeared to be independent of possible changes in plasma hormone levels. With respect to glucagon action, neither basal nor Gpp(NH)p-stimulated adenylate cyclase activities were affected in hypothyroid rats. Glucagon-sensitive adenylate cyclase activity and the apparent activation constant appeared to be unaffected. The apparent discrepancy between the results obtained from in vivo and in vitro experiments is discussed on the basis of different membrane transducing phenomena and related intracellular mechanisms underlying the biological response to hormonal stimulation. PMID- 2592755 TI - Serotonin in panic disorder: platelet uptake and concentration. AB - Platelet serotonin uptake and platelet serotonin concentrations were measured in 17 patients (5 males, 12 females) with panic attacks and 15 controls (8 males, 7 females). Higher Vmax values were found in the patient group compared with controls (65 +/- 7 vs. 47 +/- 3 pmol/10(8) platelets/min; p less than 0.05) while the affinity constant Km was not significantly different (0.6 +/- 0.1 vs. 0.5 +/- 0.1 microM). Platelet serotonin concentrations were not significantly different between the two groups (38 +/- 4 vs. 41 +/- 4 ng/10(8) platelets). These results confirm our earlier finding of increased serotonin uptake in patients with panic attacks and suggest that platelet serotonin levels are normal. PMID- 2592756 TI - Psychotropic drug prescription in general practice in Italy: a two-week prevalence study. AB - A study on psychotropic drug monitoring was carried out in Verona over a 2-week period using information obtained during consultation with 3 GPs. Psychotropic drugs accounted for 23.4% and 24.3% of all prescriptions in men and women respectively. Benzodiazepines were the most frequently prescribed: 76% and 72% of all psychotropic prescriptions respectively in women and in men. No significant association between psychotropic drug prescription and age, sex, marital status and occupation was found in the present survey. In men only, those patients with higher educational level were more likely to receive a prescription for psychotropic drugs than those with a lower educational level. About 70% of men and 60.4% of women diagnosed by the GP as having a psychiatric problem were prescribed a psychotropic drug. However, the probability of a psychotropic being prescribed, when a psychiatric problem is identified by the GP, was significantly higher (p less than 0.05) in men than in women: odds ratio 39.37 and 16.33 respectively. Psychotropic drugs were prescribed in 35% of men and in about 48% of women in which a social problem was identified by the GP. Women were about 5 times more likely to receive a prescription than men: odds ratio 12 and 2.75 respectively. A significant influence of physical ill-health and educational level on psychotropic prescription emerged: both effects were independent of sex, psychiatric morbidity and social problems. Using a logistic regression analysis, an interactive effect between sex and conspicuous psychiatric morbidity and between sex and social problems was also found. PMID- 2592757 TI - Current transfusion issues. AB - The transmissibility of HIV infection through blood transfusion has resulted in many altered ideas about blood transfusion and a re-evaluation of the indications for transfusion. Because of the risks of transfusion, the increased emphasis on proper use of hospital resources and the increasing number of managed care patients, a continuing emphasis on the appropriate indications for transfusion can be anticipated. PMID- 2592758 TI - Percutaneous transluminal coronary angioplasty: update 1988. AB - This report updates the current indications, techniques and investigational devices used in a busy interventional cardiology practice. Specific attention is devoted toward the problem areas of thrombolytic treatment of acute myocardial infarction, restenosis after angioplasty and the use of angioplasty in the treatment of multivessel coronary artery disease. PMID- 2592759 TI - Unusual presentation of pulmonary edema in a hemodialysis patient. AB - Despite the technical advances made during the last several years, chronic dialysis still is plagued by continuing problems. Intermittent volume overload is one of the most common. The radiologic evidence of pulmonary edema can be confusing in the end-stage renal disease population. The following case illustrates a hemodialysis patient with pulmonary edema whose initial chest x-ray appeared more consistent with metastatic malignancy. PMID- 2592761 TI - Nosocomial infections: new issues and strategies for prevention. PMID- 2592760 TI - Microphleboliths in vascular ectasia of the intestine: a case report. AB - Vascular ectasia is a well-established cause of obscure gastrointestinal hemorrhage. The primary method of diagnosis is mesenteric arteriography, which demonstrates a pattern of blush or intraluminal extravasation, early venous filling and microvascular distention. The most common location for this lesion is the cecum although small bowel lesions also are recognized. The following is a case of vascular ectasia affecting the jejunum, in which undescribed microphleboliths were found on microscopic examination. PMID- 2592762 TI - Anti-Ig-stimulated B lymphoblasts can be restimulated via their surface Ig. AB - Engaging AgR (surface Ig) on B lymphocytes leads to rapid inositol phosphate turnover and elevation of intracellular [Ca2+]. Continuous receptor occupancy (greater than 18 h) by anti-Ig leads to transit of most B lymphocytes from G0 to G1 stage of the cell cycle (blast transformation); a fraction of cells continue into S phase but do not proliferate continuously in the absence of growth factors. Prolonged exposure to ligand can induce receptor desensitization of some receptors. We therefore investigated whether such desensitization occurs in B cells activated by insolubilized anti-Ig. Resting B cells and anti-Ig-activated blasts were examined for their potential to elevate [Ca2+]i, maintain viability, and synthesize DNA in response to reexposure to anti-Ig. B cells and anti-Ig blasts had similar basal [Ca2+]i levels. Anti-Ig blasts retained the capacity to increase [Ca2+]i in response to anti-Ig; the magnitude of the increase was equal to or greater than that observed with resting B cells and occurred in more than 90% of cells. Isolated anti-Ig blasts subcultured in the presence of T cell derived growth factors for 3 to 5 days responded to restimulation by anti-Ig with an increase in [Ca2+]i similar to that observed in freshly isolated blasts. The B cell and B lymphoblast ion channels were found to be permeable to Ca2+ but impermeable to Mn2+. Finally, blasts restimulated by anti-Ig retained viability and incorporated low levels of [3H]thymidine for 24 h. These results suggest that AgR on activated B lymphocytes can remain functionally coupled to intracellular signaling pathways and can participate in immune responses subsequent to initial activation. PMID- 2592763 TI - In vitro evidence that Langerhans cells can adopt two functionally distinct forms capable of antigen presentation to T lymphocytes. AB - Monodisperse suspensions of epidermal Langerhans cells (LC) have been examined for their capacity to process and present Ag immediately upon extraction from mouse epidermis (fresh LC) and after 72 h in tissue culture (cultured LC). Cultured, but not fresh, LC stimulated proliferation among autologous T cells, whereas fresh, but not cultured, LC proved to be superior at processing native OVA for presentation to an OVA peptide-specific, MHC-restricted T cell hybridoma. Cultured LC were also more effective at stimulating proliferation among allogeneic T cells. However, a significant, but difficult to quantify, component of lymphocyte activation in these assays was derived from the ability of cultured LC to stimulate autologous T cells. It has been proposed that the superior capacity of cultured LC to stimulate T cells in these assays is due to the "immaturity" of freshly prepared LC--which "mature" during the 72-h culture interval. Based on the observation that fresh LC are superior at processing native protein Ag, we would amend the currently held notion that there is a "precursor-product" relationship between fresh and cultured LC to include the fact that these populations are differentially equipped to carry out distinct physiologic functions and that fresh LC should not, therefore, be considered "immature." We propose that fresh LC (in vitro equivalents of intraepidermal LC) can process native protein Ag with great efficiency, and can present these Ag in situ to memory and effector T cells (high affinity TCR interactions). Cultured LC (in vitro equivalents of LC that have migrated from skin to draining lymph node) exchange highly efficient Ag processing for acquisition of accessory molecules (surface ligands and secreted cytokines) that promote activation of unprimed T cells (including even low affinity TCR interactions). PMID- 2592764 TI - Involvement of IL-6 in mesangial proliferative glomerulonephritis. AB - In this study, we demonstrated that IL-6 was a possible autocrine growth factor for rat mesangial cells (MC). rIL-6 induced in vitro growth of rat MC at a concentration of 2 to 200 ng/ml and IL-6 activity was found in the supernatant of cultured rat MC. Northern blot analysis as well as in situ hybridization revealed that IL-6 mRNA was expressed in the cultured MC. Of urine samples from patients with mesangial proliferative glomerulonephritis (PGN) 50% were found to contain significant IL-6 activity (ranging from 30 to 126 pg/ml). Urine samples from other type of primary glomerular diseases such as minimal change nephrotic syndrome or healthy volunteers contained no detectable IL-6 activity. Only 2 of 27 urine samples from membranous nephropathy contained detectable amount of IL-6. Furthermore, there was some relationship between the levels of urine IL-6 and the progressive stage of PGN. Finally, by immunohistochemical staining using an anti IL-6 mAb, it was shown that MC in the affected glomeruli of PGN patients produced IL-6, whereas MC obtained from the patients with membranous nephropathy, minimal change nephrotic syndrome or normal kidney were not found to produce IL-6. These data suggest that deregulated production of IL-6 is involved in PGN and the measurement of urine IL-6 is helpful for the differential diagnosis of PGN as well as for monitoring the progression of PGN. PMID- 2592765 TI - Hyperreactivity of activated B cells to B cell growth factor in patients with systemic lupus erythematosus. AB - Inasmuch as B cell function is in large part determined by lymphokine-derived accessory signals, we studied the effects of recombinant IL-2 and low-molecular weight B cell growth factor (BCGF) on peripheral blood B cells activated with Staphylococcus aureus Cowan I to explain the B cell hyperfunction in patients with SLE. When S. aureus Cowan I-activated normal B cells were separated into Tac antigen (Tac-Ag)+ and Tac-Ag- cells by employing a rosette technique, IL-2 induced only the Tac-Ag+ cells to proliferate, whereas both the Tac-Ag+ and Tac Ag- cells responded to BCGF. The Tac-Ag+ and Tac-Ag- fractions of activated SLE B cells behaved like respective fractions of activated normal B cells for the pattern of response to these growth factors. It should be pointed out, however, that although the Tac-Ag+ B cells of SLE patients and those of normal controls responded to IL-2 to almost the same degree, both the Tac-Ag+ and Tac-Ag- B cells of SLE patients exhibited markedly enhanced proliferative responses to BCGF. The selectively enhanced responsiveness of a broader range of activated SLE B cells may lead to B cell hyperactivity in this disease. PMID- 2592766 TI - Activated platelets express IL-1 activity. AB - Suspensions of washed human platelets express IL-1 activity after activation with agents such as thrombin, collagen, ADP, or epinephrine as judged by the ability of the platelet suspensions to support the growth of a T cell line, D10.G4.1, which exhibits a growth requirement for IL-1. Unactivated platelets express little IL-1 activity. The IL-1 activity expressed by activated platelets appears to be entirely associated with the platelet surface. No IL-1 activity was detected in supernatants derived from suspensions of activated platelets. A mAb specific for IL-1 beta inhibited 90% of the activity expressed by thrombin activated platelets, whereas a mAb specific for IL-1 alpha inhibited approximately 20% of the activity. A control mAb was without an effect. These results indicate that activated platelets express surface-associated IL-1 activity. Platelet surface IL-1 may provide a mechanism for altering in an extremely localized and rapid manner the properties of IL-1 responsive cells with which platelets come in direct contact during processes of inflammation and vessel wall damage. PMID- 2592767 TI - Reconstitution of a functional IL-2 receptor by the beta-chain cDNA. A newly acquired receptor transduces negative signal. AB - The high-affinity IL-2R results from the noncovalent association between at least two subunits; alpha (p55) and beta (p70), both of which are capable of binding IL 2 with a low and intermediate affinity, respectively. Although the alpha-chain itself has been shown to be nonfunctional, suggestions have been made that the beta-chain mediates an IL-2 signal. To directly study the role of the beta-chain in the signal transduction, we transfected with the cDNA encoding the IL-2R beta chain a human T lymphotropic virus-I-transformed T cell line, MT-1 originally expressing low-affinity alpha-chain alone, and established a stable transformant (designated MT-beta 7) which expressed both alpha- and beta-chains simultaneously. We showed 1) MT-beta 7 manifested the high-affinity IL-2 binding, which was completely disrupted by the anti-beta chain mAb (Mik-beta 1), 2) the 125I-IL-2 crosslinking patterns of MT-beta 7 were indistinguishable from those of cells expressing the native high-affinity IL-2R, 3) MT-beta 7, but not parental MT-1, internalized the bound IL-2 and responded to IL-2 with a negative signal, i.e., inhibition of the de novo DNA synthesis. These results clearly demonstrate that the beta-chain not only participates in forming the high-affinity IL-2R with the alpha-chain but also is directly involved in the IL-2 signal transduction. PMID- 2592768 TI - Antiidiotypes against autoantibodies in pooled normal human polyspecific Ig. AB - We observed that pooled normal polyspecific human IgG for therapeutic use (IVIg) inhibited the binding of antithyroglobulin, anti-DNA and antiintrinsic factor antibodies to their autoantigens in vitro. The inhibitory effect of IVIg was dependent on interactions between the variable regions of IVIg and variable regions of the autoantibodies. Affinity chromatography of F(ab')2 fragments or of IgG containing anti-TG, anti-DNA, or anti-IF autoantibody activity on Sepharose bound F(ab')2 from IVIg resulted in the specific retention of autoantibody activity, indicating that IVIg contain antiidiotypic antibodies against human autoantibodies. Inhibition of autoantibody activity by anti-Id in IVIg in vitro is dose dependent with maximal inhibition occurring at a specific molar ratio between patient's IgG and IVIg and shows a prozone phenomenon. The relative content in anti-Id against a particular autoantibody may differ between IVIg preparations. Affinity chromatography of IVIg on Sepharose-bound F(ab')2 fragments from IVIg also resulted in specific retention of anti-TG and anti-DNA activities that were found to be present in pooled normal immunoglobulins. The presence in IVIg of anti-Id against autoantibodies from patients and from normal individuals may provide a mechanism for the suppressive effect of IVIg in human autoimmune diseases and supports the concept of a functional idiotypic network regulating autoimmune responses in man. PMID- 2592769 TI - IL-2 protects T cell hybrids from the cytolytic effect of glucocorticoids. Synergistic effect of IL-2 and dexamethasone in the induction of high-affinity IL 2 receptors. AB - IL-2-independent CD8+ rat x BW5147 T cell hybridomas are highly sensitive to treatment with 10(-6) M dexamethasone. This glucocorticoid analog induces a rapid DNA fragmentation with a pattern similar to that observed during glucocorticoid induced killing of mouse thymocytes, which suggests the activation of a similar specific endonuclease. Among these hybrids, we select variants expressing low affinity IL-2R, as measured by IL-2 binding assay and by the cell surface expression of the IL-2Rp55 Ag (rat CD25 recognized by OX-39 mAb). These OX-39+ IL 2 independent hybrids (named V type) are protected from the toxic action of dexamethasone by IL-2. The addition of IL-2 to V type cells induces the expression of a low number of high affinity IL-2R, which is strongly potentiated by the simultaneous addition of dexamethasone. Furthermore, dexamethasone is strongly synergistic with IL-2 in the induction of mRNA p55/IL-2R, which could be observed 6 h after the treatment. These data suggest that the utilization of the IL-2-R signaling pathway may induce an effective protection against glucocorticoid toxicity in mature T cells. Finally, we proved that the upregulation of IL-2R by IL-2 is strongly potentiated by glucocorticoids, which implies a new role for these agents in the immune system. PMID- 2592770 TI - Blockade of prostaglandin biosynthesis in intact mice dramatically augments the expansion of committed myeloid progenitor cells (colony-forming units granulocyte, macrophage) after acute administration of recombinant human IL-1 alpha. AB - Injection of human rIL-1 alpha in intact normal mice has positive and negative effects on myelopoiesis. Within 6 h postinjection, peripheral neutrophilia can be demonstrated. However, bone marrow and spleen cells capable of inhibiting CFU granulocyte macrophage proliferation are detected between 6 and 48 h postinjection. These myelopoietic suppressor cells belong to the monocytic lineage and are identical to inhibitory cells induced by PGE2. Treatment of mice with indomethacin, a PG synthesis inhibitor, completely blocked the generation of IL-1-alpha-induced myelopoietic suppressor cells, and significantly enhanced femoral and splenic CFU-GM proliferation after a single injection of 0.4 microgram/mouse IL-1. The peripheral blood neutrophilia observed within 6 h after IL-1 injection was delayed to 18 to 24 h postinjection in indomethacin-pretreated mice. In mice treated with four consecutive daily injections of 0.4 microgram IL 1, a sustained peripheral neutrophilia was observed. IL-1 had little effect on femoral CFU-GM in these animals, however, splenic CFU-GM was increased 7- to 10 fold by 4 to 7 days postinjection. In IL-1 plus indomethacin-treated mice, sustained peripheral neutrophilia was observed although to a lesser degree than with IL-1 alone. Marrow CFU-GM were relatively unaffected, however, splenic CFU GM were increased by 27-fold. These results indicate that the in vivo administration of IL-1 results in neutrophilia and generation of myelopoietic suppressive effects, mediated by cyclo-oxygenase pathway products. Blockade of PG synthesis by using the cyclo-oxygenase inhibitor indomethacin abrogates the myelopoietic suppressive effects associated with IL-1 administration and optimizes its myelopoietic stimulatory capacity. The inclusion of a cyclo oxygenase inhibitor may have significant relevance to the clinical use of IL-1. PMID- 2592771 TI - Mast cells chemotax to laminin with enhancement after IgE-mediated activation. AB - The increase of mast cells at sites of tissue inflammation suggests the production of local factors chemotactic for mast cells. In this report, we demonstrate that the murine mast cell line PT18 and primary mouse bone marrow derived mast cells chemotax to the basement membrane glycoprotein laminin, and that the synthetic laminin A chain-derived peptide, PA22-2, represents a region of laminin that contains a major chemoattractant site. Mast cell chemotaxis to laminin is enhanced after activation of mast cells by the calcium ionophore, A23187, or PMA and by sensitization of the cells with IgE followed by exposure to antigen. Chemotaxis is not increased in the presence of IL-3 and is independent of mast cell degranulation, as histamine release did not occur when cells were activated with PMA. Mast cell chemotaxis to laminin and its enhancement by IgE dependent mast cell activation provides a mechanism by which these cells may be attracted to sites of tissue injury. Such activity may be particularly relevant in the response of host tissues to inflammation accompanying parasitic infestations, allergic reactions, and wound healing. PMID- 2592772 TI - Macrophage cytotoxicity against schistosomula of Schistosoma mansoni involves arginine-dependent production of reactive nitrogen intermediates. AB - Lymphokine (LK)-activated macrophages are cytotoxic for multicellular larvae of the helminth parasite Schistosoma mansoni. Macrophage-mediated larval killing was found to be arginine dependent, as indicated by inhibition in the presence of exogenous arginase or the competitive inhibitor NG-monomethyl-L-arginine. Culture supernatant fluids from the larvicidal LK-activated macrophages contained nitrite, a product of activated macrophages derived by oxidation of arginine and implicated in the antitumor and antimicrobial effector function of these cells. Nitrite was not detectable in supernatant fluids obtained from nonactivated macrophages or from macrophages stimulated with LK in the presence of arginase or NG-monomethyl-L-arginine. Addition of excess iron or the reductant sodium dithionite to LK-activated macrophage cultures also inhibited larval killing in vitro, under conditions that have been shown by others to stabilize the activity of iron-containing enzymes involved in respiration. Nitrite production was not decreased under these conditions. These observations are consistent with the hypothesis that macrophage-mediated schistosomulum killing is caused, at least in part, by a mechanism proposed for tumor cytotoxicity, whereby production of reactive nitrogen intermediates triggers iron loss from critical target cell enzymes leading to lethal metabolic inhibition. In accordance, schistosomula were shown to be killed by inhibitors of mitochondrial respiration. PMID- 2592773 TI - The PSA-2 glycoprotein complex of Leishmania major is a glycosylphosphatidylinositol-linked promastigote surface antigen. AB - Polyclonal rabbit antiserum to the Triton X-114 phase material of Leishmania major, which comprises the surface and internal integral membrane proteins of the parasite, was used to screen a lambda gt11 genomic expression library. A recombinant clone producing a Mr 123,000 beta-galactosidase fusion protein was isolated. Antibodies affinity-purified on this fusion protein recognized a complex of three surface-oriented proteins of promastigotes of L. major of Mr 94,000, 90,000, and 80,000 that we have termed the promastigote surface Ag 2 (PSA 2) complex. The DNA sequence of the insert in this clone predicted the 3' end of an open reading frame encoding a hydrophobic C-terminus. The inferred C-terminal sequence was suggestive of a glycosylphosphatidyl-inositol membrane anchoring mechanism. Phosphatidylinositol-specific phospholipase C treatment of the native PSA-2 proteins caused a shift in their electrophoretic mobility with an apparent reduction in the molecular weight of the PSA-2 complex. After phospholipase C treatment these proteins also displayed the cryptic cross-reacting determinant recognized by antibodies to the Trypanosoma brucei variant surface Ag. Moreover, PSA-2, which previously partitioned in the detergent phase after Triton X-114 phase separation, became water-soluble after phospholipase C treatment. Immunoprecipitation of the PSA-2 proteins with sera directed to lectin-binding proteins indicated that these polypeptides may be differentially glycosylated. Finally, these PSA-2 proteins were recognized by sera from some patients with cutaneous leishmaniasis. PMID- 2592775 TI - Thymic involution and thymocyte phenotypic alterations induced by murine mammary adenocarcinomas. AB - A profound thymic atrophy has been observed in mice bearing large adenocarcinomas of the mammary gland. Only 2 to 5% of thymocytes remained 4 wk after tumor implantation. Although there is a slight decrease in the overall percentages of Thy-1+ cells in tumor bearers, the majority of the remaining cells are of a Thy-1 low phenotype. There was a lower percentage of double positive (CD4+, CD8+) cells, an increase of CD4+ CD8- thymocytes, similar percentages of CD4- CD8+ cells and double negative (CD4- CD8-) thymocytes in tumor-bearing mice. In addition, an increased percentage of CD3 cells could be detected in these animals. These results indicate that proportionally less immature thymocytes are present in the atrophic thymuses of mammary tumor bearers. Enhanced levels of glucocorticoids are known to produce similar effects on the thymus. However, adrenalectomy of mice followed by tumor implantation did not result in reversal of the thymic atrophy. Furthermore, a study of serum corticosterone levels in tumor bearers indicated no significant changes during tumorigenesis. A study of several parameters of bone marrow (BM) populations indicate that there is an increase in cells of the granulocyte-macrophage lineage and a decrease in lymphocytes induced by tumor-derived granulocyte macrophage-CSF. An alteration of prothymocytes in the BM is not the main cause of the thymic atrophy because BM cells from normal and tumor-bearing mice reconstituted irradiated normal mice equally well. There was no preferential recruitment of double positive cells to the spleen as indicated by no significant differences in the levels of T cells of immature phenotype including the CD4+ CD8+ population in the spleens of tumor bearers. Because no major changes were observed in tumor bearers, either at their capacity to repopulate the thymus or at the patterns of subsequent redistribution of thymocytes, it was postulated that the thymic atrophy may be caused by a direct or indirect effect of the tumor or tumor-associated factor(s). Intrathymic injections of tumor cells into young normal recipient mice resulted in a significant reduction of the thymus weight and cellularity. These data suggest that mammary tumors can secrete factor(s) that are capable of severely impairing the normal development of cells of the T cell lineage. PMID- 2592774 TI - Inhibition of immune-mediated meningoencephalitis in persistently Borna disease virus-infected rats by cyclosporine A. AB - In rats persistently infected with Borna disease virus (BDV), severe neurologic disorders and occasional death are the consequences of a T cell-mediated immunopathologic reaction in the brain. It is shown here that the pathologic alterations in the brain and as a result, Borna Disease (BD) can be prevented if animals are treated with the immunosuppressive drug cyclosporine A (CSA) under the following optimal conditions: greater than or equal to 25 mg/kg/day of CSA, started before infection and given for 4 wk. Rats treated with lower doses of CSA, for shorter periods or after infection displayed encephalitic lesions and developed BD. When CSA treatment was begun even as early as 1 day after infection, encephalitis and disease were not influenced. Immune spleen cells passively transferred into CSA-treated rats induced the disease in the recipients, whereas lymphoid cells from CSA-treated rats did not induce BD in infected cyclophosphamide-treated recipients. Antibodies were not involved in BD because rats treated with CSA revealed an inhibition of the synthesis of virus specific antibodies for all regimens of treatment used (whether successful in preventing BD or not). After i.v. challenge of CSA-treated healthy rats with BDV, antiviral antibodies at low titers could be induced in some animals; however, no encephalitis or disease symptoms could be observed at any time after infection. The same was true for rats reinfected intracerebrally with BDV after discontinuation of CSA. These results support the hypothesis that unresponsiveness and even tolerance can be induced by CSA in the presence of the foreign Ag, demonstrating the beneficial effect of this immunosuppressive drug during a persistent viral infection. PMID- 2592776 TI - Tumor growth in vivo selects for resistance to tumor necrosis factor. AB - The relationship between in vivo tumor growth and resistance to TNF in WEHI-164 cells has been examined. When a highly TNF-sensitive clone of WEHI-164 was grown in vivo in syngeneic mice it became resistant to rTNF such that a 4 to 5 log higher concentration of TNF was required to produce tumor lysis in vitro. When compared with an in vitro selected TNF-resistant variant, the in vivo selected line was significantly more tumorigenic. The resistant phenotype of both the in vivo and in vitro selected variants was stable in culture and both selected lines were also resistant to lysis by syngeneic spleen cells with natural cytotoxic activity. The parental clone and the two variants were equally sensitive to lysis by allo-CTL and expressed similar levels of MHC class I Ag. Resistance to TNF in the two variants was not a function of de novo production of TNF measured as supernatant TNF activity or TNF mRNA expression. These studies are the first to demonstrate that in vivo tumor growth results in resistance to TNF and therefore may have direct relevance to the efficacy of TNF in the treatment of human neoplasms. PMID- 2592778 TI - [Metabolic investigation of calcium renal lithiasis in adults and therapeutic advice]. AB - The various lithogenic factors are analysed. In patients with calculi it is proposed that the following are systematically carried out: -- precise analysis of the calculus even if this contains calcium to separate oxalate calculi from phosphate and carbonate calculi; -- plasma calcium, phosphate and uric acid levels together with electrolytes; -- 24 hour urine samples, on a normal diet, for calcium, creatinine, protein, phosphate, oxalate and citrate levels. Depending on the results obtained, further biological investigations may be carried out or certain aspects of the history investigated in more detail. In fact, it is essentially dietary factors which enable prevention: adequate fluid intake and normalisation of calcium, protein and sodium in take in response to laboratory abnormalities. Drug therapy is only justified in patients with recurrent calculi. PMID- 2592777 TI - Magnetic cell sorting using colloidal protein-magnetite. AB - Magnetic filtration of labelled cells as a way of separating leucocyte subpopulations was tested with a very simple and easy filtration device, using colloidal magnetite as the labelling reagent. In order to quantitate cell enrichment, a double label (both fluorescent and magnetic) was used, under conditions which labelled less than 10% of the cells in the initial sample. Up to 20 million cells were simply passed through a small magnetic filter with a hand held syringe. Depletion of labelled cells in the suspension that passed through was threefold, and enrichment of labelled cells in the wash of the filter after its removal from the magnet was approximately fivefold. Factors which limited the quality of separation are discussed. Other, more preliminary, experiments found enrichments of 15- to 30-fold with the same colloidal magnetite and hand-held apparatus when the cell labelling system was more selective. PMID- 2592779 TI - [Impotence due to venous incompetence. Research on reliable diagnostic criteria]. AB - "Venous incompetence" is thought to be an organic cause of impotence. Its diagnosis is usually based upon Artificial Erection Test (AET); now, the reliability of this procedure is contested. We tested it in 9 controls, 13 psychogenic impotent patients and 65 impotent patients presenting "venous incompetence" according AET (maintenance flow rate needed for erection--MFR greater than 75 ml/min). Organicity of impotence was evaluated by Nocturnal Penile Tumescence monitoring and by the results of a sex-therapy. AET reproducibility was tested in 24 cases. The interest to perform an intracavernous injection of 80 mg papaverine before AET was tested in 18 impotent patients. Our results confirm that MFR is the most reliable criterion for interpreting AET. But 15% of the impotent patients with a MFR greater than 120 ml/min, 32% of those with a MFR greater than or equal to 80 ml/min and 66% of those with a MFR between 80 and 120 ml/min were in fact psychogenic patients. Moreover, we found "excessive" MFR in 3 of the 13 psychogenic patients and one of the normal controls (160 ml/min). In 50% of our patients, AET results were not reproducible. Injecting papaverine before AET significantly reduces MFR, but false positive results do still exist. Some recent physiopathologic data suggest that AET performed after papaverine injection might logically be disturbed by stress. These data should incite to be cautious when interpreting AET results, and results of "venous incompetence" surgery. PMID- 2592780 TI - [A rare cause of hematuria: vesical nephrogenic adenoma]. AB - The authors report a case of a 20 year old patient with macroscopic hematuria due to a rare bladder tumor: a nephrogenic adenoma. Although a benign condition, its tendency to recurrence often means that aggressive therapy is required. Bladder ultrasonography is the principal examination for surveillance of these patients. PMID- 2592781 TI - Step-down heating of CHO cells at 37.5-39 degrees C. AB - The thermosensitizing effect of step-down heating was studied using Chinese hamster ovary (CHO) cells. Exponentially growing cells were given priming heat treatments at 43 degrees C for 45 or 90 min, immediately followed by a second exposure to a temperature ranging from 37.5 to 39 degrees C. The measured rates of cell killing, 1/D0, increased exponentially with temperature; the slopes correspond to Arrhenius activation energies of Ea = 1200 +/- 150 kJ mol-1 and Ea = 1275 +/- 125 kJ mol-1 for cells preheated at 43 degrees C for 45 or 90 min, respectively. For the temperature range 39-43 degrees C an activation energy of Ea = 561 +/- 24 kJ mol-1 was obtained for step-down heated cells (43 degrees C, 45 min followed by T = 39-43 degrees C). These results indicate that there is a 'second inflection point' at 39 degrees C on the Arrhenius curve for step-down heating of CHO cells. Data evaluation using a mathematical model published previously (H. Jung, Radiation Research, 106, 56-72, 1986) showed that the rate constant c for the conversion of nonlethal lesions into lethal events increased with an activation energy of Ea = 1520 +/- 140 kJ mol-1 in the temperature range from 37.5-39 degrees C. For 39-45 degrees C the activation energy for c was Ea = 360 +/- 26 kJ mol-1, indicating that the temperature dependence of c shows a break at 39 degrees C similar to that observed on the 1/D0 Arrhenius plot. PMID- 2592782 TI - Effect of elevation of body temperature on the electroretinogram of the rat. AB - The effect of elevation of body temperature on the electroretinogram of the rat was investigated in the dark-adapted state. A systematic decline in latency was noted as the body temperature was raised stepwise from 37 to 41 degrees C, averaging 1.9 ms degrees C-1. Maintenance of animals at a body temperature of 41 degrees C or greater led initially to increases in latency followed by decreases in amplitude. Hence, the electroretinogram shows similar changes to those reported for other sensory evoked potentials; it may therefore be a good candidate for use as a simpler model of the effects of hyperthermia on neural tissue. PMID- 2592783 TI - Interaction of heat with X-rays and cis-platinum; cell lethality and oncogenic transformation. AB - There is increasing concern for the oncogenic potential of agents used to treat cancer. Hyperthermia is one of the few modalities that does not, of itself, produce transformed foci in vitro. The adjuvant use of heat with X-rays or chemotherapy agents is an interesting approach to increasing the cell-killing potential while decreasing the oncogenicity of combined-modality therapy. Following a priming heat dose in C3H 10T1/2 cells, resistance to cell killing by a second heat dose develops and is maximal by 10 h. This is known as thermotolerance, and can be monitored by the appearance of proteins of specific molecular weight known as heat-shock proteins. By contrast, a priming heat dose does not confer resistance to killing by cis-platinum (cis-DDP). Indeed, heat potentiates the cytotoxicity due to cis-DDP. The interaction is greatest if heat and drug are applied simultaneously, but is still substantial if the drug is applied many hours after heating. The loss of interaction between heat and cis DDP occurs slowly, but by 48 h, heat and drug act independently. Thermotolerant cells are less sensitive to the induction of transformation by X-rays than previously unheated cells. On the other hand, 48 h after a heat exposure, when cells have regained their normal sensitivity to killing by cis-DDP, their sensitivity to the induction of transformation by cis-DDP has also returned to normal. PMID- 2592784 TI - Potentiation of combined BCNU and hyperthermia by pH reduction in vitro and hypertonic glucose in vivo in the BT4 rat glioma. AB - In vitro studies have shown enhanced cell killing of BCNU and hyperthermia at acutely lowered pH. In animals hypertonic glucose i.p. has repeatedly been demonstrated to reduce intratumoral pH. Effect of hyperthermia (43 degrees C for 45 min), or BCNU (3.33 micrograms/ml or both on BT4C cells were investigated in vitro, with pH 7.5, 7.0 and 6.5 in the medium during treatment. The effect of elevated glucose concentration in the medium (20 mmol/l) during treatment with hyperthermia, or BCNU, or both, was also investigated at pH 7.5. BD IX rats with transplanted BT4A or BT4An tumours on the hind foot were treated with BCNU i.p., locally applied water bath hyperthermia (44 degrees C for 45 min) or both, with or without previous glucose (6 g/kg i.p. 2 h before treatment). In vitro: low pH markedly increased cell killing by combined BCNU and hyperthermia, but pH had only a minor influence on treatment with BCNU or hyperthermia alone. Increased glucose concentration in the medium did not influence the effect of BCNU alone, hyperthermia alone, or BCNU and hyperthermia. In vivo: glucose reduced the effect of BCNU alone on BT4A tumours, but did not influence the treatment results with hyperthermia alone. However, glucose enhanced the effect of combined BCNU and hyperthermias. The effect on BT4An tumours of BCNU or hyperthermia alone were not affected by glucose, but glucose markedly enhanced the tumour effect of combined BCNU and hyperthermia. Hyperglycaemia seems to be a promising method to increase the benefit of combined hyperthermia and BCNU. However, glucose-induced altered tumour circulation could hamper the potential benefit by decreased drug uptake. PMID- 2592785 TI - Late heat damage in normal swine rectum: a comparison of thermosensitivity of rectum and oesophagus. AB - The normal swine rectum was heated using an intracavitary microwave radiator for 30 min at 43, 44, 45, 46, 47, and 48 degrees C. The animals were sacrificed 30 days later. The degree of heat injury was evaluated on a histological score system with a maximum possible damage score of 36 (100%). The scores for late damage were 8, 21, 23, 54, 58, and 74%, respectively. The 50% maximum damage was 45.8 +/- 0.5 degrees C/30 min. With the same score system, the heat damage to the oesophagus, which we have calculated previously, was evaluated and compared with that of the present data. The heat damage at the same temperature applied to the lumen was more severe in the rectum than that of the oesophagus. There was a roughly 2-3 degrees C difference in thermosensitivity between these two organs. PMID- 2592786 TI - Dielectric properties of gelatine phantoms used for simulations of biological tissues between 10 and 50 MHz. AB - The use of gelatine phantoms for simulating the dielectric properties of human tissues is suggested. These phantoms are mainly made of gelatine and water and are therefore readily prepared at a low cost. They can be poured into moulds and adopt various shapes depending on the organ to be simulated. In addition, their preservation is not critical. We have studied, at 10, 27 and 50 MHz, the variations of relative permittivity and conductivity as a function of temperature between 15 and 50 degrees C. What is shown is that those values vary both as a function of gelatine concentrations and as a function of temperature. For example, at 37 degrees C and 27 MHz, variations of relative permittivity from 87 to 100 and variations of the conductivity from 0.27 to 0.45 S/m for concentrations of 10% to 40% are observed. At the above frequency, the permittivity of human and animal tissues range between 95 and 180 and the conductivity between 0.4 and 0.6 S/m. Furthermore, the addition of sodium chloride at variable concentrations enables both conductivity and permittivity values to be modified. We propose, as 'muscle-equivalent' phantoms at 27 MHz, a phantom consisting of 20% gelatine with an electrical conductivity from 0.27 to 0.48 S/m and a relative permittivity from 90 to 93 at temperatures between 15 and 50 degrees C. These gelatine, water and sodium chloride phantoms are adapted for easy and cheap simulation of most human tissues in a temperature range from 15 to 50 degrees C, for frequencies from 10 to 50 MHz. PMID- 2592788 TI - Physical predictors of adequate hyperthermia with the annular phased array. AB - One hundred and fifty-two hyperthermia sessions in 36 consecutive patients treated with the BSD 1000 annular phased array system (APAS) are reviewed with regard to physical predictors of quality of hyperthermia. Although central tumour temperatures exceeding 42 degrees C were momentarily obtained in 62% of the sessions, it frequently proved difficult to maintain the patient at temperature for prolonged periods of time. The time to reach target temperature was negatively associated with quality of hyperthermia. Thus, of 25 sessions which required over 25 min to attain a temperature of 42 degrees C, only one was adequate (defined as central tumour temperature greater than or equal to 42 degrees C maintained for at least 30 min) as opposed to 28/69 adequate sessions when 42 degrees C was reached in less than 25 min. Physical parameters measured in the first 3 min of the session found to be associated with adequate hyperthermia include an initial rate of temperature rise at the tumour site exceeding 0.4 degrees C/min achieved with a net forward power less than 1500 W. Only three of 57 sessions not meeting these criteria were adequate. Treatment policy recommendations and recommendations for future research are made. PMID- 2592787 TI - The effect of insertion depth on the theoretical SAR patterns of 915 MHz dipole antenna arrays for hyperthermia. AB - Interstitial microwave antenna array hyperthermia (IMAAH) is presently used clinically in the treatment of cancer. This paper presents the theoretical specific absorption rate (SAR) patterns of 915 MHz microwave antenna arrays for varying insertion depths. The antennas were oriented in a 2 x 2 cm square array. Insertion depth, defined as distance from skin to antenna tip, ranged from 5.9 to 17.6 cm. Two different antenna configurations were considered. In the first the antenna had a distal section a quarter-wavelength long (resonant case), while the second had a distal section approximately 13% longer than a quarter-wavelength (non-resonant case). SAR patterns were calculated from theoretical expressions, and displayed as lines of constant SAR normalized to the maximum SAR value in the array. The results show that regions of concentrated power deposition or 'hotspots' occurred in the centre of the array and moved in a complex but predictable fashion as insertion depth was varied. For insertion depths shorter than a resonant half-wavelength, there occurred one hotspot distal to the antenna junctions. As insertion depth was increased beyond a resonant half-wavelength, the hotspot moved proximal to the antenna junctions and eventually split in two. For depths very much longer than a resonant half-wavelength a hotspot centred about the antenna junction dominated the SAR pattern. For the resonant case the maximum SAR was often along the central axis of the array, while for the non resonant case the maximum SAR was at the antennas with a local maximum on the central axis. PMID- 2592789 TI - [62d meeting of the Japanese Biochemical Society. 3-6 November 1989, Kyoto. Abstracts]. PMID- 2592790 TI - Immunologic tolerance to DNA in B cell lines from both normal and autoimmune mice. AB - We examine whether B cell lines enriched for DNA specificity from either autoimmune (BWF1) or normal mice (Balb/c) can be rendered unresponsive to autoantigen in terms of the specific suppression of direct antibody-forming cells to DNA. These B cell lines were both Lyt-1 positive and negative. Preincubation with oligonucleotide, covalently linked to mouse gamma-globulin, specifically suppressed the antigen-driven response elicited by DNA horse red blood cells in B cell lines from both strains of mice. There is a 5-fold difference in susceptibility to DNA-specific tolerance induction between B cell lines of BWF1 and Balb/c mice. Thus, B cells from autoimmune mice do not appear to have an inherent absolute defect in being rendered tolerant to autoantigen, but are relatively less susceptible to DNA-specific tolerance than nonautoimmune cell lines. PMID- 2592791 TI - B cell hyperactivity in autoimmune continuous B cell lines. AB - Generalized increase in immunoglobulin secretion, which is a prominent feature of autoimmune diseases, may be due to abnormal T cell regulation, intrinsic abnormality of B cells, or both. To investigate this question we developed nonmalignant continuous B lymphocyte lines from 20-week-old BWF1 mice and compared their growth and immune response to that of BALB/c mice cell lines. The B cell lines contain less than 1% T cells and macrophages and require growth factors from phytohemagglutinin-stimulated EL-4 lymphoma (GF) or recombinant interleukin 4 for continuous growth. No antigens or mitogens are required for growth. In the presence of 20% GF (which is optimal for BALB/c cell growth and immune function) spontaneous growth of BWF1 B cells, and spontaneous entry into G1, was similar to that of BALB/c B cells. With concentrations of GF and anti-mu which were optimal for BALB/c, the growth and immune response of isolated BWF1 B cells are no different from those of BALB/c controls, but at suboptimal doses of GF there is a significant increase of both spontaneous immunoglobulin secretion and response to anti-mu in BWF1 B cells. Thus, these autoimmune B cells are more sensitive to the effects of both T cell factors and immunoglobulin receptors stimulation. PMID- 2592792 TI - Twenty years experience with abdominal aneurysmectomy. Surgical considerations and analysis of late results. AB - This report is concerned with presentation of overall experience with abdominal aneurysmectomy, carried out upon 500 consecutive cases during the last 20 years. Emphasis is placed upon substantially improved results of the last decade in terms of survival and late mortality thus, leading to an increased spectrum of operative indications together with justified surgical aggression in the overall management of abdominal aneurysm. Elective surgery was applied upon 385 cases whereas in the remaining 115, emergency undertaking was necessary. Mortality in elective surgery was 3%. From the group of 115 emergency operations, 70 represent formal rupture with a mortality of 32% and 35 exhibited symptomatology compatible with threatening rupture. Mortality in this particular group was 8%. There was an age ranging from 38 to 87 years, with a mean age of 62.2. A definite preponderance of the disease was noted in patients between 60 and 70 years of age (17%-29%). Risk factors including heart disease, hypertension and advanced age, were responsible for the majority of deaths occurred within 30 days. Subsequent decrease of mortality should be attributed to improvements of anesthesia, monitor equipments and other supportive measures during and immediately following the operation within modern intensive care unit. Cardiac cases were the predominant cause of late death (24%) with following cerebrovascular insufficiency (8.1%), cancer (5%) and chronic pulmonary disease (6%). No particular difference in mortality was noted among the three group of patients classified according to the 60, 70 and 80 decade of their age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592793 TI - Prophylactic fasciotomy of the legs following acute arterial occlusion procedures. AB - During the 3-year period, 1983-86, 194 procedures for acute arterial occlusion were performed in our Clinic. In 43 cases following revascularization procedures, decompression fasciotomy of the leg for a developed or impending compartment syndrome was performed. Of these, three fasciotomies were done as a prophylactic procedure, before the development of the syndrome. Adequate and early fasciotomy should be considered by the vascular surgeon in every case of embolectomy when the ischemic time is greater than 6 hours, when the patient is young without sufficient collateral circulation, the history of acute arterial occlusion is precipitous, the patient is hypotensive and the back-flow is inadequate intra operatively, despite the passage of the Fogarty's catheter down to the malleolus. Skin closure after fasciotomy has to be done early, mainly with approximation of the skin edges, or to cover early the exposed viable muscles with a free split thickness autogenous skin graft. This was done in our series between the 8th and 14th postoperative days. In the case of muscle necrosis of the anterior compartment, skin coverage of the cavity has to be done later, after 2-3 weeks, as in some of our patients. PMID- 2592794 TI - Technology, coronary heart disease and its risk factors. AB - Cardiovascular diseases, predominantly coronary heart disease (CHD), are the leading public health problem in industrialized countries. They are associated with a number of variables, such as blood pressure (BP), smoking serum level of lipids, obesity etc for which technological progress is also incriminated. This relation has not been evaluated in Greece. This country is a developing one with different status of technology in different areas. In Athens it is almost similar to Western societies, but in rural areas it varies. This paper reports on morbidity of CHD and its risk factors (RF) in Greek populations with different technology. PMID- 2592795 TI - A new capillaroscopic assessment of microvascular damage vs Maricq classification in patients with isolated Raynaud phenomenon. AB - A new classification for microvascular lesions assessment by means of capillaroscopy is proposed in this research. The new method, offering a numerical score for microvascular lesions, was used in patients affected by isolated Raynaud Phenomenon (RP). RP can often be associated with scleroderma and, therefore, the new classification has been compared to the Maricq one for what concerns this connective tissue disorder. The numerical method is as sensitive as that by Maricq, but, as easily expected, its specificity is quite low. It appeared to be satisfactory also the positive predictive value of the new capillaroscopy classification combination with the clinical examination and with the immunologic biohumoral investigation. It is particularly easy to apply this method, as it presents to the examinator a restricted range of answers, for the capillaroscopic picture description, but it needs further studies in different microcirculation damages to be proved definitely valuable. PMID- 2592797 TI - Vascular manifestations of Behcet's disease. AB - The purpose of this article is to present the spectrum of vascular disease accompanying Behcet's disease. Four cases of the disease with various vascular manifestations are presented. In the first case superior vena cava syndrome due to thrombosis was the presenting symptom. In the second case foot ischemia with toe necrosis was prevalent. In the third case the patient developed recurrent aneurysmal disease in large and medium size arteries requiring successive vascular surgery, and in the fourth case the patient had SVC thrombosis and ruptured femoral aneurysm. All four patients were young males. Although vascular complications of Behcet disease are uncommon they may pose serious therapeutic problems. PMID- 2592796 TI - Acute lipidemic effect of calcium heparin in normolipemic and hyperlipemic subjects. AB - The Authors investigated the lipidometabolic effects of calcium heparin in order to assess if the antiatherogenic usefulness of the drug, recently demonstrated in the treatment of thrombosis and myocardial reinfarction, may be linked to its hypolipemiant property in addition to the antithrombotic one. The series consists of 25 normal-weight subjects (9 m, 16 f, mean age 68 +/- 5, RBW 107 +/- 3) of whom 11 were normolipemics (group A) and 14 hyperlipemics (group B) suffering from hyperlipoproteinemia of type IIA (4 cases), IIB (6 cases) and IV (4 cases). After an overnight fasting each subject was given calcium heparin (12,500 Units in a single dose subcutaneously); before and after 20', 1 hr, 2 hr and 6 hr venous blood samples were taken; for each sample plasma levels of triglyceride, total LDL-, total HDL-, HDL-3-, HDL-2-cholesterol, apoprotein CII, and apoprotein CIII were determined. In group A and B, triglycerides showed a significant reduction and total cholesterol a slight one, the "minima" being at the 1st hour after the heparinoid stimulus; the triglyceride reduction was more evident (8%) in group A than in group B (17%). In group A, total HDL-, HDL-2- and HDL-3 cholesterol decreased significantly (P less than 0.01) with a "nadir" at the 2nd hr in group B; total HDL-cholesterol did not change, whereas HDL-3-cholesterol decreased (P less than 0.05) and HDL-2 cholesterol increased (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592798 TI - Large aneurysm of the superior mesenteric artery. AB - This report describes a rare case involving a large aneurysm of the superior mesenteric artery (S.M.A.) in a 53-year-old female. Diagnosis was made by X-ray and echography and confirmed by CT-scan and arteriography showing the lesion to be atherosclerotic in origin with several thrombi on the wall of the artery. Resection of the aneurysm and venous reconstruction was performed. Recovery was uneventful. Angiography one month later demonstrated patency of the bypass. At six months the patient is presently asymptomatic. PMID- 2592799 TI - Dissection of the thoracic aorta following partial clamping. AB - A case is reported in which an extensive dissection of the thoracic aorta was observed after partial clamping during surgery on that blood vessel. The unfavourable outcome of the operation and the accurate investigation of the post mortem material suggest a lesion of the artery wall secondary to tangential clamping by Satinsky's clamp. The possible pathogenetic mechanisms of lesions induced by vascular clamping are also discussed. PMID- 2592800 TI - Angiosarcoma in a limb with arteriovenous fistulas and elephantiasis. AB - Angiosarcoma is a rare malignant tumor of the soft tissues (less than 1% of sarcoma). It may affect various parenchymae (bones, liver, breast), the soft tissues or the skin. In the latter case it may be associated with lymphedema. Onset in the arm is typical with postmastectomy lymphedema (Stewart-Treves syndrome). The forms occurring in limbs with chronic lymphedema not associated with mastectomy are much rarer, with a total of 38 cases occurring in patients with an average age of 46.8 years and with lymphedema present for an average of 20 years. The survival rate for 5 years is 16.6%. The case observed by us had the characteristic onset of the malignant neoplasm on a pre-existing "angiomatosis lymphangiomatosis" pattern also featuring angiographycally detected arteriovenous fistula. PMID- 2592801 TI - [Studies on transfer of vitamin K into human breast milk]. AB - We studied whether the administration of vitamin K to mothers could increase the concentration of vitamin K in breast milk and prevent idiopathic vitamin K deficient bleeding in breast-feeding infants. Sixty puerperal women were divided into three groups, the control group, Menaquinone-4 (MK-4) administered group and vitamin K1 administered group. We measured the concentrations of vitamin K1, MK-4 and MK-7 in maternal plasma and breast milk on the fourth day after delivery. In the MK-4 group, the concentrations of MK-4(2.13 ng/ml in plasma, 49.3 ng/ml in milk) were significantly higher than in the control group (0.28 ng/ml, 1.51 ng/ml). In the vitamin K1 group, the concentrations of vitamin K1 (49.0 ng/ml in plasma, 71.6 ng/ml in milk) were significantly higher than in the control group (1.17 ng/ml, 2.41 ng/ml). The concentration rates (milk/plasma ratio) of vitamin K1, MK-4 and MK-7 were 2.52, 5.43 and 0.52 in the control group, 1.60, 40.2 and 0.67 in the MK-4 group and 1.65, 10.8 and 0.71 in the vitamin K1 group, respectively. The concentration rate of MK-4 was higher than that of vitamin K1 and was increased by MK-4 administration. After delivery, the daily concentration of MK-4 in milk was increased from 1.69 ng/ml on the first day to 49.3 ng/ml on the fourth day in the MK-4 group. These results indicate that MK-4 is accumulated and concentrated into breast milk, and continuous MK-4 administration can increase the concentration of vitamin K in milk, preventing idiopathic vitamin K deficient bleeding in infants. PMID- 2592802 TI - [Estrogen production in epithelial tumors of the ovary--clinical and endocrinological study in postmenopausal women]. AB - Estrogen-producing activity of common epithelial tumors (54 cases) and metastatic tumors (4 cases) of the ovary was clinically and endocrinologically studied in postmenopausal patients. High serum concentrations of E1 (greater than or equal to 50 pg/ml) and E2 (greater than or equal to 30 pg/ml) were demonstrated in 78% in the group of postmenopausal patients. Mucinous tumors were more commonly associated with high estrogen levels than serous tumors. Patients with malignant tumors more frequently have a high level of serum estrogen than those with benign tumors. Estrogen decreased to normal after complete resection of the tumor, but returned to the abnormal range following a recurrence. The local-peripheral gradient of the estrogen level was noted by measuring the estrogen concentration in the blood of the affected ovarian and peripheral veins at the time of laparotomy. These results indicated that serum estrogen in the patient was originally produced in the ovarian tumor mass. The increased estrogen were reflected in such target tissues as the endometrium and vaginal mucosa. Proliferation, hyperplasia, atypical hyperplasia and even a case of carcinoma of the endometrium were observed in patients with ovarian tumors. An increase in the karyopyknotic index (KPI) of the vaginal smear, as well as uterine bleeding, could be an important signs of asymptomatic ovarian tumors in postmenopausal women. PMID- 2592804 TI - [Estrogen production in epithelial tumors of the ovary--identification of estrogen-synthesizing cells]. AB - Morphological, fine structural and enzyme histochemical investigation of common epithelial tumors of the ovary was aimed at identifying the estrogen-synthesizing cells in the stroma of the tumor. Histological changes in cell condensation or "thecosis" and cell enlargement or "luteinization" were commonly observed in the stromal area of the tumor. Two types of stromal cells were found by electron microscopic study; one had characteristic organelles of steroid hormone-producing cells, and the other had a similar cytoplasmic structure to that of fibroblastic cells. Both types of cells had lipid droplets in the cytoplasm. The former seemed to be transformed from the latter. Steroidogenesis-related enzymes such as 3 beta hydroxy steroid dehydrogenase (HSD) and 17 beta-HSD were demonstrated in the stromal cells. Electron microscopy revealed that these enzymes were localized at the intercrystal space and inner membrane of mitochondria with tubular crystal. These findings indicated that thecosis appeared in the stroma of the epithelial tumor, and the stromal cell acquired estrogen-producing potential. PMID- 2592803 TI - [Prognosis estimation score in advanced ovarian cancer]. AB - The retrospective analysis of 68 advanced ovarian cancer cases was performed mainly to see whether certain predictive factors were present which might distinguish patients with risk for recurrence or death from those with a good prognosis. Six factors, such as the mode of operation, the site of metastasis, the degree of peritonitis carcinomatosa, the rate of the decline in serum CA125. Performance Status, and pathological type were selected as factors influencing prognosis. We then tried to tally the prognosis estimation score using these factors. The correlation between this score and the survival period was noted in only patients with a survival time up to 3 years. The following formula was obtained: Y = 1.286X -3.429 [X: prognosis estimation score, Y: survival period (months)]. Cases were classified as follows according to the this score. When patients had a value equal to or less than 17.84.2% of patients died within 21 months, while if patients had a value greater than 17.34.7% of cases survived more than 36 months. On the other hand, 89.5% of cases with a survival period longer than 36 months had a prognosis estimation score greater than 18. However, there was little significant correlation between this score and the survival period in patients with survival period longer than 3 years. To conclude, although a low value for this score in advanced ovarian cancer, indicates a poorer prognosis, we cannot make an accurate prognosis for more than 3 years from this score. PMID- 2592805 TI - [Study on management of low potential malignancy ovarian tumors]. AB - Thirty-six patients with low potential malignancy ovarian tumors were treated at our hospital from 1972 to 1986. Of these, 80.6% were classified as stage I, 5.6% as stage II, and 13.9% as stage III. Sixteen patients were treated by simple total hysterectomy and bilateral salpingo-oophorectomy, 15 patients by unilateral salpingo-oophorectomy, 2 patients by enucleation of the tumor, and 3 patients by exploratory laparotomy. In stage I no difference between the survival rates for the conservative therapy group and the radical therapy group was seen. Postoperative radiation therapy was given to 4 patients with dysgerminoma, and chemotherapy was given to 13 other patients. The five-year survival rate for stage I was 91.7%, better than for stage I malignant ovarian tumors, which was 78.9%. But the five-year survival rate for stage II and stage III was 0%. Analysis indicated that: 1. Prognosis of stage I patients is so good that treatments may be done in consideration of the patient's fertility. 2. The importance of adequate postoperative treatment and of strict follow up to guard against recurrence of malignancy is important in patients with stage II or stage III disease. PMID- 2592806 TI - [Reevaluation of microdensitometry method in diagnosing osteoporosis]. AB - In order to confirm whether Inoue's microdensitometry (MD) method can assess the severity of spinal or femoral osteoporosis, the evaluation of osteoporosis in 116 patients was carried out by four methods: The MD method using X-ray picture of the hand along with an aluminium step-wedge, Itami index using X-ray picture of lumbar vertebrae, Singh index using X-ray picture of femur, and QDR method assessing BMC. The total MD score correlated significantly with the Itami index (rs = 0.691, p less than 0.001), but did not correlate significantly with the Singh index. In the group of no osteoporosis judged by the Itami index, the total MD score showed a 6.4% false positive rate. In the group of osteoporosis judged by the Itami index, the total MD score showed a 15.8% false negative rate. In order to establish a more reliable index, we developed a new H.I index (MCI X GSmin X 100). With this H.I index, the false positive rate was 1.3%, and false negative rate was 0%, and then it correlated significantly with the BMD of the lumbar vertebrae (r = 0.759, p less than 0.001). It is concluded that the MD method reflects totally osteoporotic bone loss of vertebrae but the total MD score is not so reliable, and the H.I index is a more exact indicator of osteoporosis than the total MD score. PMID- 2592808 TI - Clinical usefulness of determination of estradiol level in the menstrual blood for patients with endometriosis. PMID- 2592807 TI - 46,XY pure gonadal dysgenesis with gonadoblastoma. AB - A case of gonadoblastoma on one side in streak gonads in a phenotypic female with chromosomal 46,XY pattern is described. The histopathological resemblance between gonadoblastoma and sex cord tumor with annular tubules is discussed. The high serum testosterone level, being unrelated to the administration of human chorionic gonadotropin is valuable for the diagnosis of gonadoblastoma in an individual with dysgenetic gonads. Gonadoblastoma is frequently very small in size and is located in ectopic regions, so that laparotomy with biopsy has been stressed. The hormonal supplement for a postgonadectomized girl is also discussed. PMID- 2592809 TI - [Clinopathological study of placental hemangioma]. PMID- 2592810 TI - [Seroprevalence rate of HTLV-I in pregnant women in Osaka Prefecture]. PMID- 2592811 TI - [Angiographic arterial embolization for control of intractable postpartum hemorrhage]. PMID- 2592812 TI - [Effects of lymphokine-activated killer cells and interleukin-2 on the ascites formation and the survival time of nude mice bearing human ovarian cancer cells]. AB - Effect of intraperitoneal instillations of interleukin-2 (IL-2) and/or lymphokine activated killer (LAK) cells on the ascites formation and the survival time was examined by using a nude mice model with malignant ascites by intraperitoneal inoculation of human ovarian cancer cells (HRA) derived from ascites of a patient with serous cystadenocarcinoma of the ovary. On 28 days after tumor inoculation, all nude mice in both untreated and spleen cells only treated groups formed ascites. Two of 10 nude mice treated with IL-2 only after tumor inoculation survived without forming ascites during the experimental period. On the other hand, all nude mice treated with LAK cells only formed ascites by 14 days after tumor inoculation. When LAK cells and IL-2 were combined 5 of 10 mice survived without forming ascites during the experimental period. The survival time of the IL-2 only treated group was significantly prolonged, compared to that of medium only, spleen cells only and LAK cells only treated groups. When administration of LAK cells was followed by IL-2, the survival time was further prolonged. PMID- 2592813 TI - [Clinical application of subrenal capsule assay in ovarian cancer]. AB - The 6-day subrenal capsule assay (SRC) in normal immuno-competent mice was used to test the responsiveness of ovarian cancer to combination chemotherapy and assess the usefulness of SRC in clinical application. A total of 18 different patients in 22 different assays were studied. Twenty-one assays (95%) were evaluable. The predictive sensitivity was 50%, the predictive resistance 75% and the predictive total accuracy 55% respectively. Sensitive drugs in repeated assays in four patients were not changed. Etoposide, cyclophosphamide, cis-platin and adriamycin were sensitive. Etoposide was the most sensitive of four drugs. The response rate was 50% in the patients treated with etoposide as the first line chemotherapy and the second line chemotherapy, respectively. Patients who were treated with sensitive drugs in SRC survived longer than the patients treated with cis-platin combined chemotherapy without etoposide. The median survival time was 19 months and the mean progression free interval was 15 months. In the results of this study, the value of SRC was supported by the results of chemosensitivity tests and etoposide seems useful in chemotherapy in ovarian cancer. PMID- 2592814 TI - [Surgical management of pulmonary metastasis from carcinoma of the uterine cervix]. AB - The present study was designed to evaluate the efficacy of surgical management of pulmonary metastasis from carcinoma of the uterine cervix. We saw 609 cases of carcinoma of the uterine cervix from 1979 to 1987, and during the same period also saw 110 cases of recurrent carcinoma of the uterine cervix. Fourteen of these 110 cases were identified as having pulmonary metastasis, and in 11 of 14 cases the recurrent tumors were limited to the lung. Seven of these 11 cases underwent pulmonary resection. Six of the 7 survived more than 2 years after pulmonary resection. Among them, 1 patient has survived more than 4 years, and 1 patient more than 8 years. The tumor cells were thought to metastasize to the lung through the vertebral venous plexus (Batson's plexus) which was suggested as a metastatic route by Thomford et al. in their report on recurrent colon cancer. As a result of this study, if the recurrent tumor is clinically limited to the lung in patients with recurrent carcinoma of the uterine cervix, they should be treated by surgical resection of the pulmonary tumor. PMID- 2592815 TI - [The study on the platelet aggregation inhibition activity of placental brush border (the mechanism of platelet aggregation inhibition)]. AB - To clarify the role of placental brush border in the regulation of placental microcirculation, we investigated the platelet aggregation inhibition activity of placental brush border membrane vesicles (BBMV) and obtained the following results. 1. There was very strong platelet aggregation inhibiting activity in placental BBMV. In the 20-40 micrograms/ml protein concentration, the BBMV almost completely inhibited the platelet aggregation induced by ADP, arachidonic acid and collagen, and in the 100-150 micrograms/ml protein concentration, the BBMV almost completely inhibited the platelet aggregation induced by ristocetin. 2. There existed a very strong ADP degrading activity (ADPase activity) in the placental BBMV. The platelet aggregation activity of ADP was completely lost when ADP was preincubated with the placental BBMV. 3. The placental BBMV inhibited platelet malondialdehyde (MDA) production. With the 20 micrograms/ml and 100 micrograms/ml protein concentrations of placental BBMV, 22% and 65% of platelet MDA production was inhibited respectively. PMID- 2592816 TI - [The study of cyclic maintenance chemotherapy with cisplatin, adriamycin, and cyclophosphamide (cyclic PAC chemotherapy) in patients with advanced ovarian cancer]. AB - The efficacy of two methods of chemotherapy in the treatment of patients with advanced ovarian cancer was compared on the basis of survival curves; one consisted of remission induction therapy alone with a combination of cisplatin (CDDP), adriamycin (ADM) and cyclophosphamide (CPM) (induction PAC therapy), and the other consisted of induction PAC therapy and additional maintenance therapy with cyclic PAC (cyclic PAC therapy). The subjects of the study were patients with advanced ovarian cancer in stages III and IV. Sixty-eight patients received induction PAC therapy alone and seventeen patients received both induction and cyclic PAC therapy. Demographic factors such as age at initial presentation, the stage of cancer (III or IV), surgical procedure, histological classification, number of courses of induction PAC, response rate, site of residual tumor after surgery and induction PAC therapy, and reduction rate of CA125 were compared in the two groups. When analyzed by the chi 2 test, none of these factors was significantly different in the two groups. Patients in the induction PAC therapy group received a median total dosage of CDDP 360 mg, ADM 235mg, and CPM 2.246mg. Patients in the cyclic PAC therapy group received CDDP 592mg, ADM 490mg, and CPM 4.642mg. Thus, the dosage of anticancer agents administered to the latter group was about twice as great as that administered to the former group. According to the Kaplan-Meier method, survival rates for the induction PAC therapy group were 88.2% for one year, 50.0% for two years, 28.0% for three years, and 8.8% for five years. The median survival period was 23 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592817 TI - [Effect of human recombinant interleukin-1 alpha on glycosaminoglycan and collagen metabolism in cultured human chorionic cells]. AB - To investigate the correlation between chorioamnionitis and premature rupture of membranes (PROM), the influence of human recombinant interleukin-1 alpha (hrIL-1) on the metabolism of glycosaminoglycans (GAGs) and collagen in cultured human chorionic cells was examined and the following results were obtained. 1. When chorionic cells were incubated with D-[6-3H] glucosamine, the cells biosynthesized and rapidly secreted GAGs into the medium. After a 24-hr incubation, approximately 75% of total GAGs was distributed in the medium fraction, and more than 75% of these GAGs were found to be a high mol. wt (more than 1 x 10(6] hyaluronic acid. 2. hrIL-1 enhanced the biosynthesis and secretion of hyaluronic acid in a dose dependent manner, but hrIL-1 did not change the mol. wt of hyaluronic acid. In addition, no remarkable effect of hrIL-1 was exerted on the biosynthesis of the sulfated GAGs, therefore the consequential decrease in their relative concentrations was observed. 3. Collagen biosynthesized by chorionic cells increased linearly in proportion to the incubation period, and after a 12-hr incubation, about 75% of the tritilated collagen was secreted into the medium fraction. hrIL-1 did not modulate production of the collagen and noncollagenous protein in the cells. 4. hrIL-1 induced collagenase production in chorionic cells and significantly accelerated its production in a dose dependent manner, without affecting cell proliferation. The stimulatory effects of IL-1 on the biosynthesis of hyaluronic acid and collagenase are connected with the decrease in tensile strength observed in PROM. Thus, it is proposed that IL-1 from effused leukocytes in fetal membrane plays an important role in PROM with chorioamnionitis. PMID- 2592818 TI - [Study of the mechanism of tumor marker CA125 in serum]. AB - Ascites fluid, chest effusion, cyst fluid, and serum mainly obtained from malignant-ovarian-cancer patients were applied to quantitate the concentration of the tumor marker CA125. The same procedure was also performed for ascites, cyst fluid, and serum mainly obtained from benign-ovarian-tumor patients. To know how CA125 proceeds from tumor cells into the circulation, a CA125-producing, ovarian cancer-cell line (SHIN-3) was transplanted sub-cutaneously into nude mice. Then the relationship between the grown tumor size and CA125 concentration in serum was analyzed and the histo-pathological background was also evaluated. Quantitative analysis of the ascites and cyst fluid showed no remarkable difference between the malignant-tumor patients and benign ones: however, the CA125 concentration in serum of malignant-tumor patients was up to 90 times higher than in benign ones. The proceeding ratio of CA125 in its productive site (cyst fluid, for example) to that in the serum of patients with malignant lesions was 24 times as high as with benign lesions. No relationship between tumor sizes and the CA125 concentration in serum in nude mice was observed. And in the mice which had high CA125 in serum, the capsules around the tumor tended to be destroyed and vessel infiltration by tumor cells was remarkable. PMID- 2592819 TI - [Preventive effect of urinastatin on cisplatin-induced nephrotoxicity]. AB - Anticancer chemotherapy with cisplatin (CDD) as the main drug (combined with adriamycin (ADM) and cyclophosphamide (CPM), PAC therapy) was performed on patients with ovarian cancer. Urinastatin (US) was concurrently administered to assess its effectiveness in preventing CDDP-induced nephrotoxicity. Twenty-two patients with gynecological malignant tumor were treated with PAC therapy, and of these, twelve concurrently received US. The ten who did not receive US served as the control. As a rule, one course of PAC therapy consisted of 50mg/m2 CDDP, 50mg/m2 ADM and 500mg/m2 CPM. Before the administration of CDDP, US 100,000 units was administered by I.V. drip infusion and after the administration, US 400,000 units was again administered by I.V. drip infusion at a speed of 100,000 to 200,000 units/hour. A total of approximately 3,500ml of fluids was administered I.V.. Each course of PAC therapy took 7 to 14 hours to complete. The control group underwent PAC therapy in a regimen not including US. As indexes of nephrotoxicity, serum levels of BUN, creatinine (Cr), and creatinine clearance (Ccr), and N-acetyl-beta-glucosaminidase (NAG), gamma-glutamyl transpeptidase (gamma-GTP), and arylamidase (AA) activity in the urine was determined before treatment and at days 1, 2, 3, 7, 14, and 21 after the initiation of PAC therapy. Changes in serum BUN, Cr, and Ccr levels after CDDP administration in the group with and the group without concurrent US were similar. Urinary gamma-GTP, AA, and NAG activity remained unchanged after CDDP administration in the group with concurrent US. In contrast, in the group without US, this urinary enzyme activity was transiently increased after CDDP administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592820 TI - [The obstetric prognosis and neonatal outcome of pregnant women with psychiatric disorders]. AB - Obstetric prognosis and neonatal outcome of pregnant women with psychiatric disorders were retrospectively investigated. 1. Out of 1.472 deliveries at Saga Medical School from April 1983 to July 1988, there were fourteen cases (0.95%) involving psychiatric disorders-six of epilepsy, one of anxiety neurosis and seven of schizophrenias. 2. Total blood loss was relatively great in four epileptic patients. However, the general prognosis for each was good and the neonatal outcome was uneventful. 3. As for schizophrenic patients, six out of seven cases grew worse during the pregnancy and four in the postpartum period. Three cases underwent cesarean section due to their mental illness. 4. We made inquiries about the postpartum life of schizophrenic mothers and children, and received five answers (70.1%). It was found that schizophrenic mothers could not bring up the baby by themselves; they needed the help of their husbands and their own mothers. It is concluded that consistent management by both psychiatrist and obstetrician from the antepartum period to postpartum life are required for psychotic mothers and their children to obtain a favorable prognosis, and a follow-up system is desirable for the physical as well as the mental growth of the infants. PMID- 2592822 TI - [A morphological study of glandular formation and epithelialization from normal human endometrial epithelial cells in vitro]. AB - We employed basement membrane extracts (BME) prepared from Engelbreth-Holm-Swarm tumor for in vitro culture of normal human endometrial cells (E-cells) and observed a process of glandular formation followed by epithelialization. E-cells isolated enzymatically were cultured in BME-coated culture dishes and morphological observations were carried out. The results were as follows: 1) E cells cultured on BME had a globular shape, grew in a helix-like pattern, and formed a tubular glandular structure, rising perpendicularly above the BME surface. 2) Following the glandular formation, 2 weeks after the beginning of the culture, E-cells on the top of the glandular structure spread out in all directions and formed an epithelial-like monolayer cell sheet on the surface of the BME mimicking superficial luminal epithelialization. 3) Glandular E-cells were columnar in shape, had numerous surface microvilli, and faced a lumen which was sealed by a tight junction complex of cells. Superficial E-cells were cuboidal in shape, with mild polarized organelles, nuclei, and abundant microvilli and the surface was entirely covered with BME. These results indicated that this culture system using a BME could be useful in studying the physiology of the human endometrium in vitro and the mechanism of reproduction. PMID- 2592821 TI - [Combination therapy of intravenous ritodrine and magnesium sulfate to inhibit premature labor]. AB - Thirty-seven patients in premature labor with intact membranes were treated as follows. Ritodrine was given as a primary tocolytic agent and magnesium sulfate was added adjunctively when the uterine contractions could not be controlled even when the administration of ritodrine exceeded 250mmg/min (14 of 37 cases) (combination therapy group). Prolongation of pregnancy for more than 48 hours and delivery beyond 37 weeks were achieved in 89% and 68% respectively. These results were more satisfactory than those obtained with the isoxsuprine treated group (122 cases). The incidence of discomfort due to nasal obstruction was low in the ritodrine group, but side effects such as palpitation and hot flush occurred more commonly in the combination group. No life-threatening side effects were observed throughout this study. Twelve out of 37 cases (32%) were delivered before 37 weeks. Neonatal morbidity was more frequent in this group delivered before 33 weeks of gestation. These included respiratory distress, hypotension, hypoglycemia, and hypocalcemia. Moreover, two babies born from mothers treated with ritodrine and magnesium had ileus-like symptoms. These data suggest that this combination therapy is effective as far as the tocolytic purpose is concerned. However, special attention must be paid to adverse maternal and neonatal effects as well. PMID- 2592823 TI - A method for differentiating between monozygotic and dizygotic twins. AB - It has become possible to accurately differentiate monozygotic from dizygotic twins. In this study DNA fingerprinting was performed with new mini-satellite DNA as a probe. Identical DNA fingerprints from each twin indicate a monozygotic relationship and different fingerprints indicate a dizygotic relationship. In a case of dizygotic twins, the DNA fingerprints digested with HinfI indicated a monozygotic relationship, whereas the DNA fingerprints digested with MboI showed a dizygotic relationship. PMID- 2592824 TI - [Anatomically corrected malposition of great arteries (ACM): prenatal diagnosis]. PMID- 2592825 TI - [Clinical experience of a totally implantable venous catheter for gynecologic cancer patients]. PMID- 2592826 TI - [27th meeting of the Japan Society for Cancer Therapy. 25-27 October 1989, Nagoya. Abstracts]. PMID- 2592827 TI - [Biochemical changes in the airways after antigen inhalation challenge in asthma]. PMID- 2592828 TI - [Environmental factors affecting pathogenesis of bronchial asthma]. PMID- 2592829 TI - [Type III and type IV allergy: summer-type hypersensitivity pneumonitis]. PMID- 2592830 TI - [Pulmonary opportunistic infections in patients with autoimmune diseases]. PMID- 2592831 TI - [The clinico-pathological study of acute hepatic failure]. PMID- 2592832 TI - [Two cases of CREST syndrome complicated with primary biliary cirrhosis and their correlation with HLA-DR]. PMID- 2592833 TI - [A case of malignant struma ovarii complicated with thyroid cancer]. PMID- 2592834 TI - [A report of two cases with recurrent cranial neuritis showing multiple cerebral white matter lesions in MRI-CT]. PMID- 2592835 TI - [A case of argininosuccinate synthetase (ASS) deficiency diagnosed by the measurement of ASS with the liver biopsy specimen]. PMID- 2592836 TI - [Systemic lupus erythematosus in three sisters]. PMID- 2592837 TI - [Secondary amyloidosis associated with overlap syndrome of rheumatoid arthritis, progressive systemic sclerosis and polymyositis]. PMID- 2592838 TI - [A case of panhypopituitarism due to multiple myeloma]. PMID- 2592839 TI - [A case of Bartter's syndrome associated with gout and gouty kidney]. PMID- 2592840 TI - [A case of HTLV-I associated myelopathy (HAM) with Sjogren's syndrome]. PMID- 2592841 TI - [Dental anthropological study of the Central American Indians]. AB - The purpose of this study was to evaluate the dento-craniofacial morphology and the occlusal characteristics in the Central American Indians from the dental anthropological point of view. The sample consisted of cephalograms, pantomograms, dental casts, photos and records (anthropometric measurements and oral examinations) which were taken from 210 modern Central American Indians and 212 ancient Central American Indians. The results were summarized as follows: 1. Craniofacial morphology: The modern Central American Indians showed; (1) smaller facial height and shorter depth of the cranial base and jaws than those of the Caucasians. (2) posterior position of peri-orbital structures, and smaller values of anterior facial height in comparison with the Japanese, which were similar to the Peruvian Indians. (3) shorter depth of the jaws and prominence of the chin than the ancient Central American Indians. 2. Dental arch form and tooth size: The modern Central American Indians had; (1) wider dental arches than the Caucasians, while sharing similar values with the Peruvian Indians and the Japanese. (2) smaller incisors, larger premolars and molars in the mesio-distal crown diameter compared with the Caucasians. (3) smaller teeth in the mesio distal crown diameter than the ancient Central American Indians. 3. Occlusal conditions: The modern Central American Indians showed a good mesio-distal relationship between the upper and lower first molars in 70 percent. PMID- 2592842 TI - [Application of superplastic titanium alloy for denture base--Part 1. Adaptability of the titanium alloy denture base]. AB - The adaptability of the upper complete denture base made from superplastic alloy 90Ti-6A1-4V was investigated by measuring the space between the master model and the denture base. The denture bases showed a high adaptability with the space less than 0.1 mm, whereas after curing resin for denture, it became worse especially with the heat-curing resin. In addition, the thinnest area of the denture base was observed at the middle of the plate with 38% reduction in thickness, and distortion of the base plate of 0.55mm thickness by curing resin was found to be nearly the same as that of type 304 stainless steel plate of 0.50 mm thickness. PMID- 2592844 TI - Computerized nurse charting. AB - Computerized nurse charting programs have been used at LDS Hospital for over two years. These programs allow the nurse to create nurse care plans for the management of the patient, and chart on the computer actions and information which support the documentation of the management of the patient according to the care plan created for the patient. Computer terminals have been placed at the patient's bedside to facilitate the use of these programs. This paper describes the programs available at LDS Hospital and several evaluation studies which have been performed to measure the efficacy of the programs. The evaluation studies indicated an increase in the level of documentation completeness and accuracy by the nurse but at some minor expense to time available to the nurse for patient care. Evaluation of the need for bedside terminals versus centrally located terminals showed an overwhelming desire by the nurse in favor of the bedside terminal. It was also found that data was entered more timely with less waiting when bedside terminals were available. Physician acceptance of the nurse charting system was found to be favorable. PMID- 2592843 TI - [Effect of subgingival plaque control by direct irrigation technique--2. Clinical and microbiological changes after irrigation with acrinol or benzalkonium chloride solution]. AB - The aim of the study was to evaluate the effect of the subgingival plaque control by direct irrigation. Twelve adult patients with periodontal pockets of 4 mm or more received an initial treatment. The patients were followed by irrigation using the device called Pocket Irrigator PT-01 with 0.05% acrinol solution or 0.025% benzalkonium chloride solution. The clinical and microbiological parameters were recorded prior to the irrigation and immediately after, at 1 hour, 1 day and 1 week after the irrigation. The Plaque Index, Gingival Index, gingival crevicular fluid and probing depth were used as clinical parameters. Samples of the subgingival plaque were collected with sterilized paper points from the periodontal pockets. The samples were examined by dark field microscopy with the Petroff-Hauser counting chamber with a magnification of 1,500x. The total number of bacteria and the proportion of the motile rods and spirochetes of the pockets were examined. All clinical parameters showed no significant changes after the irrigation. Intracrevicular irrigation by both acrinol and benzalkonium chloride solution significantly reduced the relative number of bacteria and the percentage of spirochetes/motile rods, when compared to those before the irrigation on day 1, though the differences did not persist on day 7. Thus, only by the single irrigation of the deep pockets with acrinol or benzalkonium chloride, the beneficial effects did not appear to continue clinically and microbiologically for a week. PMID- 2592845 TI - Automated cardiovascular analysis and treatment (ACAT). PMID- 2592846 TI - Computers in medicine: liability issues for physicians. AB - Physicians routinely use computers to store, access, and retrieve medical information. As computer use becomes even more widespread in medicine, failure to utilize information systems may be seen as a violation of professional custom and lead to findings of professional liability. Even when a technology is not widespread, failure to incorporate it into medical practice may give rise to liability if the technology is accessible to the physician and reduces risk to the patient. Improvement in the availability of medical information sources imposes a greater burden on the physician to keep current and to obtain informed consent from patients. To routinely perform computer-assisted literature searches for informed consent and diagnosis is 'good medicine'. Clinical and diagnostic applications of computer technology now include computer-assisted decision making with the aid of sophisticated databases. Although such systems will expand the knowledge base and competence of physicians, malfunctioning software raises a major liability question. Also, complex computer-driven technology is used in direct patient care. Defective or improperly used hardware or software can lead to patient injury, thus raising additional complicated questions of professional liability and product liability. PMID- 2592847 TI - Caustic ingestion. AB - Caustic ingestion is a serious medical problem affecting anywhere from 5,000 to 15,000 persons per year. The factors influencing the type and seriousness of the burn are numerous. Correct diagnosis using endoscopic technique is imperative in choosing the proper treatment whether it be medical or surgical. Stricture is the most common complication with rates from 2% to 4%. PMID- 2592849 TI - Transient cortical blindness following cerebral angiography. AB - Transient cortical blindness following cerebral angiography was previously assumed to result from embolism or other factors impairing cortical perfusion during angiography. Contrast medium-induced disruption of the blood-brain barrier and a direct neurotoxic effect by contrast media have been proposed as a potential mechanism of neurotoxicity. Support of this concept has been provided by reports that demonstrate blood-brain barrier damage with postangiography computerized tomography in patients experiencing various acute neurologic sequelae of cerebral angiography including one case of transient cortical blindness. We report a case of transient cortical blindness following cerebral angiography in which computerized tomography documents blood-brain barrier disruption limited to the occipital lobes. PMID- 2592848 TI - The effects of calcium on bone mineral density in postmenopausal women with colles fractures. AB - The increased incidence of fracture in postmenopausal women may be attributable, in part, to osteoporosis. Prediposing factors other than age include genetic constitution, physical activity, alcohol and caffeine abuse, and dietary calcium deficiency. A group of 15 postmenopausal women between the ages of 43 and 85 years were analyzed for bone mineral density within 4 weeks of an acute fracture of the distal radius. Dual photon absorptiometry scanning was performed on the first through fourth lumbar vertebrae. Results indicate that bone mineral densities below the fracture threshold (0.965 g/cm2) were seen in 9 of 15 (60%) patients. Each woman was given 1500 mg/day calcium supplementation for 1 year. At 1 year, each woman was contacted for a follow-up bone mineral density analysis. While no significant increase in bone mineral density was seen, calcium supplementation appeared to inhibit further bone loss. The results of this study support previous work which has indicated that supplemental calcium may be beneficial in combatting age-related bone loss. PMID- 2592850 TI - Pseudocyesis and depression. Etiological and treatment considerations. AB - Pseudocysesis, or false pregnancy, is generally classified as a conversion symptom and is usually treated as such with little success. Depression, however, is a commonly associated phenomenon and is typically neglected in the formulation and treatment of this disorder. This report presents a case study in which the patient was referred for evaluation of pseudocyetic symptoms, but depression was judged to be the underlying problem. Antidepressant therapy was instituted and found to be effective in ameliorating the pseudocyetic symptoms. Treatment implications of pseudocyesis as an artifact or concomitant of depression are discussed. PMID- 2592851 TI - ECG of the month. Trees or forest? Ventricular bigeminal rhythm; AV dissociation. PMID- 2592852 TI - Zinc treatment of Wilson's disease. PMID- 2592853 TI - Treatment of Wilson's disease with zinc. VI. Initial treatment studies. AB - Eleven patients with newly diagnosed Wilson's disease were treated with zinc acetate as their sole anticopper therapy. Treatment duration was 8 to 37 months. Three of the patients had symptoms; in eight who were presymptomatic, diagnosis was made because of affected siblings who had symptoms. All patients did well clinically. Copper absorption was suppressed, as reflected by blockade of absorption of orally administered copper 64. Values for 24-hour urine copper and nonceruloplasmin plasma copper (freely available copper) were reduced. Values for liver-derived serum enzymes were also generally reduced in patients who had pretreatment elevations. Percutaneous liver biopsies were done initially and repeated in seven of the patients after 12 to 35 months of zinc therapy. In five of these patients a second biopsy specimen showed higher levels of copper than the first. In three of these five a third biopsy 6 to 23 months after the second revealed liver copper values that either had returned to the baseline value or were lower. One patient's initial biopsy specimen showed active inflammation, which subsided with therapy. All of the biopsies revealed histologic scarring typical of cirrhosis, and this did not appear to change over the course of therapy. We conclude that hepatic copper may increase temporarily during early zinc therapy but that the accumulated copper is sequestered in a nontoxic form. On the basis of animal studies we postulate that this sequestered copper is primarily bound to the high levels of hepatic metallothionein induced by zinc. Zinc appears to be a reasonable option for the initial treatment of patients with Wilson's disease, particularly those with presymptomatic disease. PMID- 2592854 TI - Treatment of Wilson's disease with zinc. VII. Protection of the liver from copper toxicity by zinc-induced metallothionein in a rat model. AB - Patients with Wilson's disease often have a further increase in hepatic copper when given zinc as an initial treatment, although there is no associated clinical deterioration. To better understand this situation an animal model was developed in which copper-loaded rats are treated with zinc administered subcutaneously. In the presence of equal amounts of copper loading in liver, control rats show hepatic damage but zinc-treated rats do not. Zinc-treated rats have much higher levels of hepatic metallothionein. Gel filtration studies reveal that much of the hepatic copper in zinc-treated rats is in this metallothionein fraction, whereas the copper in control animals is primarily associated with fractions of high or low molecular weight. Subcutaneous zinc therapy also induces intestinal, but not brain, metallothionein. We interpret these findings to indicate that zinc therapy protects against copper toxicity in liver by induction of hepatic metallothionein, which sequesters copper in a nontoxic form. PMID- 2592855 TI - Effects of tumor necrosis factor on PMN chemotaxis, chemiluminescence, and elastase activity. AB - Tumor necrosis factor (TNF) has been proposed as an important mediator of the inflammatory response in acute lung injury. To better understand polymorphonuclear leukocyte (PMN) activation during acute lung injury, we evaluated the effects of TNF on several in vitro PMN functions, including chemotaxis, chemiluminescence, and elastase activity. In the chemotaxis assay using a modified Boyden chamber, TNF alone or with N-formyl-methionyl-leucyl phenylalanine (FMLP, 10(-8) mol/L) did not alter PMN migration. TNF suspended with 1% zymosan-activated serum (ZAS) increased PMN migration at low concentrations and decreased migration at high concentrations (control 99 +/- 4.8 microns, n = 9; TNF 0.1 ng/ml 135 +/- 9.4 microns, n = 5, p less than 0.01; TNF 1000 ng/ml 62 +/- 7.5 microns, n = 5, p less than 0.01). In the chemiluminescence assay, TNF (1000 ng/ml) induced a 3-fold increase in the PMN chemiluminescent response. However, TNF incubated with PMN did not cause an increase in supernatant elastase activity. These data reveal TNF induced the production of PMN reactive oxygen species as evidenced by an increased chemiluminescent response. Whereas TNF increased chemotaxis at low concentrations in the presence of 1% ZAS, high concentrations of TNF similar to levels detected in septic shock caused a decrease in chemotaxis that might contribute to retaining PMN in sites of inflammation. It is thus suggested that TNF may contribute to inflammation by stimulating the production of PMN-reactive oxygen species and modulating-PMN chemotaxis. PMID- 2592856 TI - Heparin cofactor II activity in plasma during pregnancy and oral contraceptive use. AB - Inhibition of thrombin by heparin is mediated by at least two plasma proteins, antithrombin III, and heparin cofactor II. The plasma titer of heparin cofactor II was significantly elevated in both pregnant women and users of oral contraceptives. PMID- 2592857 TI - Bacterial lipopolysaccharide acts on human endothelial cells to enhance the adherence of peripheral blood monocytes. AB - The effects of bacterial lipopolysaccharide on the adherence of human peripheral blood monocytes (M0) to endothelial cells (ECs) were investigated in a quantitative adherence assay as an in vitro model of M0-EC interactions. ECs exposed for 2 hours or longer to 0.10 to 10 micrograms/ml lipopolysaccharide demonstrated significant increases in the levels of M0 adherence compared to control cells. By contrast, lipopolysaccharide added directly to adherence assays or preincubated with M0 did not increase M0 adherence to ECs. The effects of interleukin-1 (IL-1) were similar to the effects of lipopolysaccharide in that they acted solely on ECs to enhance M0 adherence and accelerated the rate of EC adherence to M0. Lipopolysaccharide did not increase EC adherence of M0 by causing damage or extracellular release of soluble mediators. The increase in M0 EC adherence by the chemotactic peptide formyl-methionyl-leucylphenylalanine (FMLP) was quite different from that by lipopolysaccharide and IL-1. FMLP rapidly induced M0 to become more adherent to ECs and plastic surfaces but was unable to act on ECs and enhance M0 binding. Thus M0-EC interactions are enhanced by the direct effects of FMLP on M0, whereas the actions of lipopolysaccharide and IL-1 are entirely focused on ECs and can be distinguished by differing characteristics and cellular targets. PMID- 2592858 TI - Interleukin-1 regulation of prostaglandin E2 synthesis by the papillary collecting duct. AB - Interleukin-1 (IL-1) has been demonstrated to cause a natriuresis and diuresis in experimental animals. This effect is associated with an increase in prostaglandin E2 (PGE2) excretion and is prevented by pretreatment with cyclooxygenase inhibitors. Micropuncture studies have shown IL-1 inhibition of sodium reabsorption by the rat papillary collecting duct (PCD), a nephron segment capable of abundant PGE2 synthesis. The current study examined the effect of IL-1 on PGE2 synthesis by cultured PCD cells and the mechanism by which such regulation occurs. IL-1 markedly increased PCD cell PGE2 synthesis within 15 minutes of exposure in a dose-dependent manner. Preincubation with saturating concentrations of arachidonic acid abolished IL-1 stimulation of PGE2 synthesis. PCD cells labeled with tritiated arachidonic acid released significantly more arachidonic acid within 5 minutes of exposure to IL-1 as compared to control cells. These data demonstrate that IL-1 directly stimulates PGE2 synthesis by PCD cells and that this effect occurs by enhancement of arachidonic acid release. PMID- 2592859 TI - The effect of sodium on amiloride-tobramycin synergy in Pseudomonas cepacia. AB - Amiloride combined with subinhibitory concentrations of tobramycin is synergistic against Pseudomonas cepacia in vitro. It is known that amiloride blocks transmembrane sodium (Na+) flux in eukaryotic cells, but the mechanism of action in bacteria is unknown. Amiloride-mediated Na+ gradient changes might affect transcellular tobramycin transport, resulting in synergy between these two drugs. To examine this hypothesis, we studied the effect of extracellular [Na+] on amiloride-tobramycin synergy with a reference strain of P. cepacia. Control growth in Mueller-Hinton broth (MHB) alone, MHB supplemented with 200 mmol/L NaCl, and MHB dialyzed against a Na+-free solution was determined by absorbance at 650 nm over 3 hours. Inhibition in the presence of amiloride, tobramycin, or a combination was expressed as percentage of control growth. Growth in the presence of tobramycin alone was significantly higher in MHB + NaCl than in MHB or dialyzed MHB (81% +/- 5%; vs 57% +/- 5%; 35% +/- 4%; mean +/- SEM, respectively, p = 0.003). Growth in the presence of amiloride alone was not significantly different in the three media (84% +/- 4%; 80% +/- 3%; 80% +/- 1%; respectively, p = 0.746). Percent control growth was significantly lower when the two drugs were combined, but results were not statistically different among the three media (3.5% +/- 3%; 0.2% +/- 0.8%; 4% +/- 1%; respectively, p = 0.604). We conclude that growth inhibition of P. cepacia in the presence of tobramycin is antagonized by increasing extracellular [Na+]. This antagonistic effect of [Na+] is reversed by amiloride. Changes in [Na+] do not appear to directly affect amiloride tobramycin synergy in P. cepacia. PMID- 2592860 TI - The learning mystique. PMID- 2592861 TI - Holistic principles: not enhancing the old but seeing a-new. A rejoinder. PMID- 2592862 TI - Designing practice activities. AB - When selecting or devising practice activities on basic information for students, teachers should consider these guidelines: 1. Prevent memory overload by introducing new information cumulatively. 2. Build retention with delayed review and discriminated practice. 3. Reduce interference effects by separating confusing elements from one another over time. 4. Emphasize relationships between components of an algorithm and the algorithm itself, between familiar and new information, and between items and their location, if relevant. 5. Reduce processing demands by introducing components before the algorithm or strategy itself and by introducing easier information first. 6. Require quicker responses to foster automaticity. As noted in the introduction to this essay, these six guidelines have not been investigated across all topics or across all populations. Further research is needed. In the meantime, the guidelines serve as an initial response to Pellegrino and Goldman's (1987) question about the form practice should take for students with learning disabilities. The guidelines could be applied to a wide range of content for which automaticity is an ultimate goal--letter-sound correspondences, word reading, numeral identification, math facts, word meanings, geography facts, and so forth. PMID- 2592863 TI - Toward solving the problems of misidentification and limited intervention efficacy. AB - The learning disabilities (LD) field has "boxed itself in" and, as a result, is not making satisfactory progress in reducing misdiagnoses and improving intervention efficacy. Evolving trends are not seen as reflecting fundamental changes in thinking and practice. With a view to the future, the position is taken that the field must (1) address causality in differentiating LD from other learning problems, (2) expand prevailing approaches to individualizing instruction so that intrinsic motivation is accounted for in a systematic and comprehensive manner, and (3) move beyond piecemeal programs to implement a fully integrated and coordinated continuum of interventions. PMID- 2592864 TI - A rural-based transition model for students with learning disabilities: a demonstration. AB - This article presents a project that provides and coordinates transition services to high school students with learning disabilities. The Central Nebraska Goodwill Industries Transition Model is a four-phase process initiated during the freshman year of high school. Involvement begins with assessment and evaluation activities that culminate in the development of a transition planning component to the Individualized Education Plan. A variety of service providers offer assistance to satisfy identified transition needs. Unique features of this model include the development of a regional transition advisory council, personal growth groups for participants, and a private, nonprofit rehabilitation center as the coordinator of transition services. PMID- 2592865 TI - An examination of the homework practices of teachers of students with learning disabilities. AB - This study examined the homework practices of 88 teachers of students with learning disabilities. While the findings indicated that the respondents were using several quality homework practices, some problems were noted. Suggestions for improving the homework procedures of teachers of students with learning disabilities are presented. PMID- 2592866 TI - Relationship between social perception and peer status in children with learning disabilities. AB - This study was undertaken to examine the social perceptual skill deficit theory in explaining the low peer acceptance of children with learning disabilities. The quality of tests measuring social perception was also examined. Thirty 9- to 12 year-old children with learning disabilities and a matched control group were given two measures of social perception: a laboratory task and a behavior rating scale. The behavior rating scale was completed by the children's teachers. In addition, the Peer Acceptance Scale (Bruininks, Rynders, & Gross, 1974) was administered to assess peer status. Results showed that the children with learning disabilities differed significantly from their nondisabled peers on each of the three measures-the children with learning disabilities obtained lower social perception and peer acceptance scores. However, the relationships between sociometric status and social perception varied as a function of task. A small but significant correlation wa found between the behavior rating scale and peer status. The laboratory task was not correlated with either the behavior rating scale or peer status. Results are discussed in terms of the psychometric properties of laboratory versus naturalistic measures of social perception and the importance of establishing the external validity of social skill measures by correlating them with outcome measures such as peer status. PMID- 2592867 TI - Vocational education and students with learning disabilities. AB - This inquiry focuses on the status of nearly 500 students with learning disabilities in 17 state-operated regional vocational-technical schools in a northeastern state. The inquiry addressed four primary concerns: patterns of assessment, career choice, school marks, and attendance. The data indicate that a variety of instruments were used in the assessment process and that the overall grade equivalent levels of attainment ranged between fifth- and seventh-grade levels. Children defined as learning disabled participated in a large number of vocational trade specialties and some 50% or more had school marks indicating that they were passing in these areas. Attendance was high. Many children with learning disabilities successfully perform in competitive vocational education programs designed to produce proficiency at the level of journey person. PMID- 2592868 TI - Neuropsychological profiles of children with learning disabilities and children with documented brain damage. AB - This study sought to identify clusters or subtypes of children with learning disabilities (LD) and documented brain damage (BD) on the basis of a comprehensive neuropsychological battery. Sixty subjects, 24 with LD and 36 with BD, participated in the study. The standard scores for several measures from the Intermediate Battery of the Halstead-Reitan Neuropsychological Battery and other select measures were submitted to Q-Technique factor analysis for the entire sample. Five clusters were determined. No one cluster was composed exclusively of LD or BD subjects, with the proportions of LD and BD varying considerably from one cluster to the next. There were some qualitative differences between the clusters, while quantitative differences also figured prominently. PMID- 2592869 TI - Visual persistence and adult dyslexia. AB - Visual persistence was investigated in adults with and without dyslexia in order to determine whether the adults with dyslexia demonstrate problems similar to those found in childhood dyslexia. Using a temporal separation threshold measure and procedures derived from signal detection theory, sensitivity to sequentially presented form information was determined for the two types of adults. The results showed that the sensitivity of the adults with dyslexia was impaired relative to that of the nondisabled adults when parts of a test stimulus were presented to adjacent retinal areas. This result suggests that, under certain conditions, visual persistence is longer for adults with dyslexia. The results are discussed within the context of a recent theory of dyslexia (Lovegrove, Martin & Slaghuis, 1986) that incorporates the operation of sustained and transient visual mechanisms. PMID- 2592870 TI - Visual and auditory coding confusability in students with and without learning disabilities. AB - The nature of visual and auditory coding processes in students with learning disabilities (SLDs) and student controls (SCs) was examined with a letter matching task on four types of successively presented letter pairs: identical (A,A), visually confusable (P,R), auditorily confusable (F,S), and neither visually nor auditorily confusable (N,T). Two delay intervals (0 and 2 seconds) were used between the presentation of the first and second letters. Analysis of decision latencies on the nonidentical letter pair trials revealed that with initial exposure to the task, the SLDs responded more slowly than SCs, but their general confusability patterns (visual and auditory) were similar. With additional practice, overall decision latencies were comparable for the two groups, while confusability differences emerged: SCs showed maximal visual confusability at a 0-second delay and maximal auditory confusability at a 2 second delay, while SLDs did not. Evidently, SLDs make less extensive use of visual and auditory coding processes compared to SCs. PMID- 2592871 TI - Exclusive arrangements in the hospital industry. AB - There have been numerous antitrust cases concerning exclusive hospitals privileges. The plaintiff often alleges both that he was foreclosed from the market and that an illegal tying agreement exists. This paper, which draws heavily from the cases, concludes both that the relevant market for hospital based physicians is national and that the impact on competition is minimal. The hospital frequently initiates the exclusive arrangement which suggests that efficiency is enhanced. Our analysis also shows that the tying claims are generally unpersuasive. However, exclusive arrangements on occasion may be a device to exclude competitors. Finally, economic criteria are developed to help determine the desirability of particular exclusive arrangements. PMID- 2592874 TI - Informating, not automating, the medical record. AB - The author suggests that reference should be made in the future to the need to informate and not to automate the medical record. The reason for this recommended semantic change is first to avoid the mistaken notion that the computerization of medical records will reduce the number of personnel processing medical information. Instead, personnel will shift their attention from rote clerical activities to analytic activities made possible by the creation of new data bases by computers. These new data bases, a byproduct of informating the medical record, describe work processes and lend themselves to analytic activities which will enhance quality and efficiency in hospitals. The recent availability of report generators on commercial Laboratory Information Systems (LISs) mark their transition from automating to informating systems. One example of an ad hoc report used to enhance quality and efficiency in the clinical laboratories is the throughput report. PMID- 2592873 TI - A computer aid for choosing HMOs: design of a new interface. AB - This paper reports on a new interface design. The presentation is similar to a newspaper style, allowing a familiar format and advertisement. In addition, the design includes steps to ease data collection, features to help users influence others in the organization, and a dynamic allocation of menu lists that reflect user's knowledge and previous interest. PMID- 2592872 TI - A microcomputer system for clinical signal analysis of vestibular laboratory. AB - A vestibular laboratory system was implemented for clinical testing and medical examination of patients with balance disorders. Programs for analysis of postural control and eye movements were made for a microcomputer. The microcomputer system can be used by a nurse without technical education. The system has now been used for two years at the laboratory. PMID- 2592875 TI - Cognitive match interface design, a base concept for guiding the development of user friendly computer application packages. AB - The authors present a base concept which unites the various prescriptions for creating and implementing a user friendly computer system. Making the system operate and interact with the user in a manner which parallels the flow of the user's own thought processes is the key issue. The authors illustrate this concept with examples from a system they recently developed to create and store patient records for the health care industry. Additionally they outline a procedure for creating patient/client data storage systems. PMID- 2592876 TI - Effect of sonic versus ultrasonic instrumentation on canal preparation. AB - The instrumentation time, and the resulting root canal angulation change and shape after using ultrasonic, sonic, and hand instrumentation techniques were studied in the mesial canals of 55 extracted human mandibular first and second molars. After instrumentation, the roots were sectioned horizontally in the apical, middle, and coronal thirds and evaluated for shape, mesial and distal canal widths, and canal diameter. MM3000 and hand were significantly faster than the other techniques (p less than 0.005). MM3000 resulted in less angulation change than the Enac (p less than 0.005). Hand instrumentation was judged to have given the best shape (p less than 0.01). PMID- 2592877 TI - A comparison of Flex-R files and K-type files for enlargement of severely curved molar root canals. AB - A double exposure radiographic technique is introduced and used to evaluate the magnitude of apical canal transportation that occurs during preparation procedures. The balanced force technique and a step-back method for cleaning and shaping root canals were evaluated in mesiobuccal root canals from 80 extracted human molar teeth with curvatures ranging from 30 to 73 degrees. Pre- and posttreatment file positions were examined from clinical and proximal radiographic views by computer digitization. Statistical analysis indicated significantly less apical transportation with the use of the balanced force technique when compared with a step-back technique in canals exhibiting both more and less than 45 degrees of curvature. PMID- 2592878 TI - The comparative leakage behavior of reverse filling materials. AB - This study compares the in vitro apical seal achieved with thermoplasticized gutta-percha used with and without a sealer cement and that achieved with dental amalgam and a varnish liner following an apicoectomy and a Class I preparation of single root teeth. The teeth were immersed in methylene blue dye for 10 days, were sectioned longitudinally, and the amount of leakage was determined. No difference in leakage was found between the apical seals achieved with thermoplasticized gutta-percha used with a sealer cement and that obtained with dental amalgam with varnish. The leakage found with thermoplasticized gutta percha used without a sealer cement was significantly greater. PMID- 2592879 TI - Absorbed radiation by various tissues during simulated endodontic radiography. AB - The amount of absorbed radiation by various organs was determined by placing lithium fluoride thermoluminescent chip dosimeters at selected anatomical sites in and on a human-like X-ray phantom and exposing them to radiation at 70- and 90 kV X-ray peaks during simulated endodontic radiography. The mean exposure dose was determined for each anatomical site. The results show that endodontic X-ray doses received by patients are low when compared with other radiographic procedures. PMID- 2592880 TI - Emergency pulpotomy: pain relieving effect with and without the use of sedative dressings. AB - Seventy-three teeth with acute irreversible pulpitis were subjected to emergency pulpotomies. After removal of the coronal portion of the pulp, a sterile cotton pellet or zinc oxide-eugenol cement was placed against the remaining pulp tissue. The cotton pellet was either dry or moistened with camphorated phenol, cresatin, eugenol, or isotonic saline. This gave six different groups of treatment following the pulpotomy. All teeth were sealed with zinc oxide-eugenol cement. By means of questionnaires, symptoms were recorded after the anesthetic effect was gone and also at 1, 7, and 30 days after treatment. A total of 70 patients (96%) reported pain relief. Three patients did not experience relief and returned for pulpectomy. After the first postoperative day, no pain was reported by any of the patients. The frequency of discomfort decreased from 11% 1 day postoperatively to 1% 30 days after the emergency treatment. There was no difference in recorded symptoms among the six treatment groups. Thus, removal of caries, pulpotomy, and sealing of the cavity apparently was a reliable means to relieve pain. The use of the various dressings did not contribute to the relief of pain. PMID- 2592881 TI - A comparison of apical seal: chloroform versus eucalyptol-dipped gutta-percha obturation. AB - Three groups of extracted teeth were obturated using gutta-percha and lateral condensation. In one group the gutta-percha was dipped in chloroform before condensation. In a second a eucalyptol dip was used. No dip was used in the third group. A dye penetration study was done to compare leakage among the three groups. The teeth were cleared for viewing and measurements of dye penetration were made using a stereomicroscope. Statistical analysis using Kruskal-Wallis one way analysis of variance of the results showed no significant difference among test groups at the 0.05 level. PMID- 2592882 TI - A statistical analysis of surgical and nonsurgical endodontic retreatment cases. AB - A total of 1300 endodontic patient charts were analyzed for factors that may have contributed to the failure of the original treatment or the success of the retreatment. Of those surveyed, 667 had recall information of 6 months or more and were used to consider success rates. The remaining cases were analyzed for other information. The findings were tabulated and analyzed by computer for significant relationships. The overall success rate for retreatment was 65.6% with an additional category of "uncertain" of 18.3%. Surgical treatment was necessary to retreat 53.5% of the cases. PMID- 2592883 TI - Conservative treatment of root perforations using apex locator and thermatic compactor--case study of a new method. AB - Endodontic perforation, a serious complication in dental practice, is among the most common problems associated with endodontic procedures. Recommended methods of treatment are surgical or conservative using calcium hydroxide paste. A method in which perforations can be obturated immediately after their detection is described. The method utilizes an apex locator for measurement and detection of the perforation and a two-step treatment of thermatic compaction for filling the root canal as well as the perforation. A number of cases with a long follow-up are presented. PMID- 2592884 TI - Endodontic overextension produced by injected thermoplasticized gutta-percha. AB - Obturation of the root canal space with an inert filling material and creation of a hermetic apical seal has been shown to improve the success rate of endodontic therapy. A new technique of canal obturation with injection-molded thermoplasticized gutta-percha has been shown to create a good apical seal. However, failure to determine accurately the canal working length and create an apical stop in sound dentin can lead to overextension of the gutta-percha into the periradicular bone. A case of significant overextension of gutta-percha using this new technique is presented along with its ramifications and management. PMID- 2592886 TI - The effects of the scheme for BCG vaccination of schoolchildren in England and Wales and the consequences of discontinuing the scheme at various dates. AB - The aims of this paper were to estimate the numbers of tuberculosis notifications in young white adults which will be prevented in the next 25 years by the schools BCG vaccination scheme, and to assess the numbers of additional notifications if the scheme were to be discontinued. Assuming that in the white ethnic group in England and Wales the decline in tuberculosis notification rates (8-10% per year for ages less than 45 years) and efficacy of BCG vaccination (75-80%) are maintained, it is estimated that the scheme for BCG vaccination of schoolchildren with its present coverage will prevent 217 notifications in those aged 15-29 years in 1993, 119 in 1998, and 69 in 2003. The epidemiological consequences of stopping the BCG in schools scheme, whenever this occurs, would be a substantial slowing of the rate of decline of tuberculosis notifications, confined almost entirely to the 15-29 years age group, for a period of about 15 years, after which the steeper decline would resume. If the scheme stopped at the end of 1991 the annual number of additional notifications would slowly increase to a maximum of just over 80 about 15 years later, and then decrease. For stopping at the end of 1996 the maximum annual number of additional notifications would be about 50. PMID- 2592885 TI - Risk factors in chronic obstructive pulmonary malfunction and "chronic bronchitis" symptoms in Beijing district: a joint study between Japan and China. AB - A cross sectional study of risk factors in respiratory diseases was carried out in August 1986, in Beijing, China. Inhabitants greater than or equal to 40 years old were selected at random from a rural area, a residential area and an industrial area, using a two stage sampling method. The analysis presented here is based on the sample population of adults who (1) were prepared to be interviewed, using the British Medical Research Council's questionnaire translated into Chinese (n = 3423) and (2) had lung function measurements at the same time (n = 3373). Obstructive lung disease was defined as forced expiratory volume in 1s (FEV1) less than 68% of forced vital capacity (FVC). Seven variables were considered as potential risk factors or confounding factors: area of residence, sex, age, cigarette smoking, history of respiratory disease, socio economic status and familial component. A modified binary variable regression method developed by Feldstein was used for the adjustment of rate ratios. The adjusted prevalence of obstructive lung disease was highest in the rural area and lowest in the residential area(s). An increase in age, cigarette smoking, low socio-economic status and positive history of respiratory diseases were associated with significantly higher rates of impaired pulmonary function. The other measured factors did not appear to be related to impaired pulmonary function. PMID- 2592887 TI - Computer held chronic disease registers in general practice: a validation study. AB - Lists of patients receiving repeat prescriptions for epilepsy, diabetes, thyroid disease and asthma were compared with chronic disease registers stored on seven practice computers. Diabetes was the most accurately recorded disease: the names of 72% of patients receiving medication for this condition appeared on the relevant disease registers. Agreement between the two data sources was 68% for thyroid disease, 58% for asthma and 49% for epilepsy. The levels of accuracy are not yet high enough for the computerised chronic disease registers to provide an accurate estimate of the prevalence of these conditions, but new system developments suggest a more optimistic outlook for the future. PMID- 2592888 TI - Randomisation by cluster and the problem of social class bias. AB - For randomised population trials the unit of randomisation is normally the individual person. In some situations, however, investigators take other groups as basic unit and one such design is cluster randomisation. Considerable attention has been given to this design recently in statistical and epidemiological literature. The Edinburgh randomised trial of breast cancer screening is an example which takes general practices as clusters of patients. The experience of this trial is reported here. Mortality from all causes, cardiovascular disease and lung cancer over the first 5 year period of follow up are examined. We found that spurious mortality differences were present in the analyses, which do not allow for socio-economic status. From examination of methods of adjusting for this, we conclude that allowance can be made at the analysis stage, and it is intended that this approach will be adopted when breast cancer mortality is analysed in the Edinburgh trial. Nevertheless, we recommend that for future studies with outcome related to socio-economic status, randomisations which use this design be stratified by socio-economic criteria where this is feasible. PMID- 2592889 TI - Social class and risk factors for coronary heart disease in the Federal Republic of Germany. Results of the baseline survey of the German Cardiovascular Prevention Study (GCP). AB - The relationship between social class and seven important risk factors for coronary heart disease has been evaluated utilising data from the German Cardiovascular Prevention Study baseline survey. Of German residents aged 25 to 69 years, 16,430 were randomly selected from both the six intervention regions and the Federal Republic of Germany to undergo the screening procedures between 1984 and 1986. Among males the prevalence of cigarette smoking and lack of physical activity was associated with social class. For females, overweight and physical activity demonstrated a strong social gradient. No relationship existed between social class and hypercholesterolaemia. The prevalence of Type A behaviour was significantly higher for the upper social classes. The number of CHD risk factors per study subject increased with decreasing social class. Predicted cardiovascular mortality was clearly higher for the lower social class among males in general and for females younger than 60 years. These findings point to the need for risk factor intervention strategies focusing more on the lower social classes in order to achieve more adequate prevention of coronary heart disease. PMID- 2592890 TI - The incidence of cancer in schizophrenic patients. AB - A cohort of 6168 schizophrenic patients was followed from 1957 to 1984 to determine the incidence of cancer in these patients. In the male schizophrenic patients the incidence of cancer was found to be significantly reduced in comparison with the general Danish population. This reduction was especially marked for cancer in the respiratory system, cancer of the prostate and cancer of the bladder. In the female patients the overall incidence of cancer did not differ from that of the general Danish population, but there was an increased risk of cancer of the digestive tract, especially cancer of the pancreas and a slight increase of the risk of breast cancer. In the female patients the risk of respiratory cancers and cancer of the female genital organs, especially cancer of the uterine cervix, was reduced. These alterations of the incidence of cancer in schizophrenic patients cannot be ascribed to differences in diagnostic accuracy. As a possible explanation of these findings a reduced exposure to well known carcinogens such as cigarette smoke may be relevant. We speculate that exposure to neuroleptics such as phenothiazines and reserpine may also be part of the explanation for the findings. PMID- 2592891 TI - Increased obstetric activity: a new meaning to "induced labour"? AB - This study examines the possible reasons for increased obstetric activity in Denmark over the past 25 years. Since 1960 there has been a substantial increase in the average number of hospital admissions (from 10 to 32 per 100 deliveries), in deliveries diagnosed as complicated (from 15 to 49%), and above all in major interventions at delivery (from 4 to 22%). In spite of this increase in activity there is no evidence that the postwar trend of decreasing perinatal mortality has been further improved during the period of study. It seems possible that the rising level of activity is the result of increasing availability of new technology, decreasing numbers of deliveries and unchanged obstetric staffing levels, with an increased tendency to diagnose and intervene in "at risk" pregnancies. There is a need to determine how the current level of obstetric activity has arisen. Since there is evidence for an increased expectation of intervention by pregnant women, the theory of supplier induced demand may be among the leading contenders to be tested. PMID- 2592892 TI - Sexual behaviour of young people and the risk of HIV infection. AB - A survey of 16-21 year old people in Somerset was undertaken to find out about their sexual behaviour prior to mounting a local education campaign on AIDS. A representative sample of 400 people, using quota sampling in 40 randomly selected electoral wards, completed a schedule structured part self administered questionnaire. Of these, 371 (92%) considered themselves heterosexual. Nearly half (47%) of the 16 year olds had engaged in sexual intercourse, rising to 89% by the age of 21. Mean frequency of sexual intercourse among the sexually active is 62 per year. The frequency of partner change decreases with increasing age for non-virgins from 2.1 for 16 year olds to 1.5 partner changes per year for 21 year olds (mean frequency 1.7 per year, ie, a new partner every 7 months). This level of sexual activity could eventually give rise to HIV prevalence rates similar to those found in Africa, i.e., 15-100 HIV antibody positive per 1000. PMID- 2592893 TI - School meals, school milk and height of primary school children in England and Scotland in the eighties. AB - In a nutritional surveillance system of primary school children in England and Scotland we assessed the possible effects on height gain of changes in school meals and school milk policies following the 1980 Education Act (No. 2). Mean height and height gain were estimated separately for English and Scottish samples from 1982 to 1984, and for a selective sample of inner city areas with a high proportion of ethnic minorities from 1983 to 1985 in children from 5.00 to 9.99 years. Children receiving free school meals were smaller than children paying for school meals or receiving a meal prepared elsewhere, while children receiving free school milk were of similar stature to other children in the study. The rate of growth was assessed in children receiving school meals or lunches prepared at home, and in those for whom arrangements changed during the study period; it was also assessed in those children for whom school milk was available, not available, or for whom the provision changed. No consistent association was found between provision of school meals or school milk and the rate of growth in the three samples studied when stratified according to poverty status and ethnic background. We conclude that this observational study does not provide any evidence that the current availability of school meals or school milk increases the rate of growth of primary school children in any social stratum. PMID- 2592894 TI - Damp housing and childhood asthma; respiratory effects of indoor air temperature and relative humidity. AB - In a questionnaire survey of a random sample of 1000 children aged 7 years, a significantly greater proportion of those living in homes reported as damp were affected by wheeze (22% v 11%), day cough, night cough, and chesty colds. Simultaneous estimation of relative humidity in the bedrooms of 778 children and continuous 7 day recordings of ambient temperature and humidity in a stratified sample of 317 bedrooms showed no association with the same respiratory symptoms. No correlation was found between bedroom conditions and baseline ventilatory function or exercise induced reduction in FEV1. These results run counter to the widely held belief that indoor temperature and humidity are important determinants of respiratory ill health, although they do not directly exclude effects due to mites or moulds, whose survival is determined by the humidity of their respective microenvironments. PMID- 2592895 TI - Prospective study of factors predicting uptake of smoking in adolescents. AB - Risk factors for the uptake of cigarette smoking were examined prospectively in 2159 non-smoking secondary schoolchildren aged 11-13 who participated in a survey in 1983 and were followed up 30 months later, by which time 35 per cent had taken up smoking. In a multivariate logistic model, the strongest predictors to emerge were prior experimentation with cigarettes and sex, with more girls (41%) than boys (30%) starting to smoke. Other predictors of taking up smoking were being uncertain about smoking in the future, reporting having been drunk, having a boy or girl friend, believing teachers and friends would not mind if they took up smoking, and giving lower estimates of prevalence of smoking among teachers. Parental smoking behaviour and attitudes, beliefs about the effects of smoking on health, opinions about smoking and perceived strictness of parents did not predict take up of smoking when other variables were controlled for. The odds of taking up smoking varied from 0.24 (risk = 0.19) for a child with the most favourable combination of risk factors to 3.49 (risk = 0.78) for a child with the worst prognosis. These results differ from those of many cross sectional studies and hence indicate the importance of a prospective approach to this type of research. PMID- 2592896 TI - On statistical methods for analysing the geographical distribution of cancer cases near nuclear installations. AB - There is great public concern, often based on anecdotal reports, about risks from ionising radiation. Recent interest has been directed at an excess of leukaemia cases in the locality of civil nuclear installations at Sellafield and Sizewell, and epidemiologists have a duty to pursue such information vigorously. This paper sets out to show that the epidemiological methods most commonly used can be improved upon. When analysing geographical data it is necessary to consider location. The most obvious quantification of location is ranked distance, though other measures which may be more meaningful in relation to aetiology may be substituted. A test based on distance ranks, the "Poisson maximum test", depends on the maximum of observed relative risk in regions of increasing size, but with significance level adjusted for selection. Applying this test to data from Sellafield and Sizewell shows that the excess of leukaemia incidence observed at Seascale, near Sellafield, is not an artefact due to data selection by region, and that the excess probably results from a genuine, if as yet unidentified cause (there being little evidence of any other locational association once the Seascale cases have been removed). So far as Sizewell is concerned, geographical proximity to the nuclear power station does not seem particularly important. PMID- 2592897 TI - A prospective study of some aetiological factors in limb reduction defects in Sweden. AB - Two groups of infants with limb reduction defects were studied: all such infants born in Sweden 1983-1986, and infants with severe reduction deformities born in 1973-1981. Data on the use of oral contraceptives, intrauterine devices, and drugs, and on maternal smoking were retrieved from information collected in early pregnancy as a part of routine maternity health service records. It was not possible to substantiate the association, described repeatedly in the literature, between limb reduction defects and the use of oral contraceptives just before or in early pregnancy. Various explanations for this discrepancy are discussed. An association with maternal diabetes was seen but not with drugs used for thyroid disease. A weak and statistically non-significant association with maternal smoking was found for severe limb reduction defects. PMID- 2592898 TI - Appendicectomy in Asian children. PMID- 2592899 TI - Risk factors for breast cancer by mode of diagnosis: some results from a breast cancer screening study. AB - We have investigated factors affecting the probability that a woman with breast cancer participating in a mammographic screening programme will be diagnosed by the screen. Data from a large American case-control study, with subjects drawn from women participating in an annual screening programme, were used. During the screening programme, 409 cases were identified, the mode of diagnosis being screen detection for 331 and interval detection for 78. No significant relationships were found between mode of diagnosis and age, age at menarche, oral contraceptive use, age at first live birth, age at menopause or history of maternal breast cancer. There was a non-significant trend for particular mammographic patterns to be associated with interval detection. However relative risk of breast cancer and probability of interval detection were observed to increase about the time of the menopause. These results suggest that the 3 yearly mammography programme being introduced in the UK might be improved if an extra examination was included around the time of the menopause. PMID- 2592900 TI - Incidence of invasive cervical cancer in the Swiss canton of Vaud, and a note on screening. AB - Age adjusted incidence rates (World standard) from invasive cervical cancer in the Swiss canton of Vaud decreased from 17.7/100,000 in 1968-70 to 9.9/100,000 in 1983-85. The decline was substantial in younger middle age, but no appreciable trend was observed in women over 70. This is consistent with available interview based information on the pattern of cervical screening in the Swiss population. Although there was no organised screening programme in Switzerland, over 80% of women aged 20-44 and 65% of those aged 45-64 reported one or more screening smears over the previous 3 years, compared to only 22% of women aged 65 or over. In the last calendar period, there was an apparent increase in the incidence of invasive cervical cancer (from 2.5 to 6.1/100,000) in women aged 25-29. Although based on small absolute numbers, this is in agreement with incidence and mortality data from other countries, and may therefore confirm a change in risk factor exposure in younger women. PMID- 2592901 TI - Epidemiology of babies dying at different ages from the sudden infant death syndrome. AB - An analysis of data from the United Kingdom multicentre study of postneonatal mortality has been made to assess whether there are causally distinct groups of babies dying from the Sudden Infant Death Syndrome (SIDS), and to develop explicit risk factor profiles for the subgroups. The 303 SIDS babies in the multicentre study were divided into four subgroups by age at death: weeks 1-7, 8 15, 16-23, and 24 or more weeks. Contrasts between these subgroups with respect to 28 epidemiological characteristics and to pathology findings were investigated. Significant contrasts in the number of previous pregnancies, duration of the 2nd stage of labour, gestational length, family finances and repair of housing were found. Overall, very strong evidence of epidemiological differences was found (chi 2(9) = 29.3, p less than 0.001), and of contrasts in the nature and degree of any acquired terminal disease. It is concluded that there are different causes of SIDS with different distributions according to age at death. PMID- 2592902 TI - Life table methods applied to use of medical care and of prescription drugs in early childhood. AB - Life table methods were applied to analyses of longitudinal data on the use of medical care during the first 5 years of life among all 1701 children born in a Swedish semirural municipality. Cumulative proportions of the children who had used particular types of medical care or prescription drugs at least once by certain ages were estimated. By the fifth birthday, 98% had made at least one visit to any physician and 82% at least one visit to a paediatrician. By the fifth birthday at least one prescription for antibiotics had been purchased at a pharmacy by 82%; and 33% had been admitted to inpatient hospital care at least once (excluding immediate postnatal care). Acute conditions and more chronic diseases were also studied using these methods. At least one visit to a physician at a primary health care centre had been made for acute otitis media in 65% of 5 year olds and for atopic dermatitis in 8%. PMID- 2592903 TI - The effect of leisure time physical activity on the risk of pre-eclampsia and gestational hypertension. AB - STUDY OBJECTIVE: To assess the relation between leisure time physical activity (LTPA) during the first 20 weeks of pregnancy and the risk of developing pre eclampsia and gestational hypertension. DESIGN: Case-control study carried out over a 28 month period with retrospective data collection. SETTING: Six hospitals in Quebec City and four hospitals in Montreal. PARTICIPANTS: 172 women with pre eclampsia, 254 with gestational diabetes, 505 controls. All were primiparous, with no history of high blood pressure before pregnancy (unless due to oral contraceptive use), or during the first 20 weeks of gestation. Cases were defined using recognised criteria, and 97% of those eligible agreed to be interviewed. Controls delivered in same hospital immediately after cases and had no more than one reading of elevated blood pressure during pregnancy; 96% of those eligible agreed to be interviewed. MEASUREMENTS AND MAIN RESULTS: Participants were interviewed in hospital a few days after delivery using a questionnaire. Information was collected on type, frequency and average duration of any LTPA performed regularly during the first 20 weeks of pregnancy, together with medical, obstetric and sociodemographic details. It was found that women who performed regular LTPA had a reduced risk of pre-eclampsia (adjusted RR 0.67, 95% CI 0.46-0.96) and gestational hypertension (aRR 0.75, 95% CI 0.54-1.05), and the relative risks decreased as the average time spent in LTPA increased (aRR for pre eclampsia among women with low, moderate and high energy expenditure: 1.00, 0.77 and 0.57, p = 0.01). The same trend was present for gestational hypertension (1.00, 0.80 and 0.71, respectively, p = 0.08). CONCLUSIONS: Leisure time physical activity during the first half of pregnancy is likely to reduce the risk of pre eclampsia and gestational hypertension. PMID- 2592905 TI - Changes in diet and coronary heart disease mortality among social classes in Great Britain. AB - Coronary heart disease (CHD) mortality has declined in Britain since the early 1970s and followed a reduction in dietary fat intake in the population. We attempted to determine whether there have been changes in dietary fat intakes by social classes and to see whether they correspond to social class changes in CHD mortality, where the greatest reduction has been in the upper social class groups. Dietary fat intake was specially obtained by social class on a household basis from the National Food Survey (NFS) for 1974 and 1981. The decline in saturated fat intake and increase in polyunsaturated fat is shown to have occurred in each social class group, although it was not possible to examine the data separately for men and women. In contrast, the decline in the proportion of current smokers between 1974 and 1980 (from the General Household Survey) was greatest in the higher social classes. Rates of CHD mortality showed the greatest decline among men in social classes I & II over the period 1969/73 to 1979/83. However, despite some problems in the interpretation of the data collected by the NFS, this study shows that recent social class trends in dietary fat intakes are unlikely to account for the differential changes in CHD mortality. Changes in the prevalence of smoking among social classes are more consistent with the change in CHD mortality. PMID- 2592904 TI - Confounding variables in studying the effects of maternal alcohol consumption before and during pregnancy. AB - STUDY OBJECTIVE: to investigate the relationship between alcohol consumption and pregnancy outcome. DESIGN: prospective randomised cohort survey with follow up sample stratified on level of alcohol intake. SETTING: antenatal clinic of large maternity hospital in Western Australia. PARTICIPANTS: 2002 randomly selected pregnant women recruited over 3 year period for questionnaire survey (58% in 1st trimester, 33% in 2nd trimester, 8% in third trimester at recruitment). Only 19 refused participation. Stratified subsample of 665 women followed up, of whom 60 had miscarriage, stillbirth or neonatal death. Subsample was selected on basis of prepregnancy alcohol consumption. INVESTIGATIONS AND MAIN RESULTS: All 2002 women completed a comprehensive questionnaire on demographic, lifestyle, health (including diet) and obstetric factors. The stratified subsample was followed through pregnancy and data were collected on obstetric course and infant outcome. Results showed that beer, wine and spirits drinkers differed significantly in maternal characteristics, nutrition and other important variables such as smoking. Women with stillbirths or miscarriages drank more beer than those with live births, though total levels of alcohol intake did not differ. Beer drinkers were less likely to reduce their consumption in pregnancy than other drinkers if they also smoked more than 20 cigarettes per day. CONCLUSIONS: Studies of effects of maternal drinking must include extensive information on the variables examined in this study or conclusions relating to maternal drinking in pregnancy are likely to be invalid. PMID- 2592906 TI - Predicting 15 year chronic bronchitis mortality in the Whitehall Study. AB - Fifteen year chronic bronchitis mortality was investigated among 17,717 male civil servants aged 40-64 years participating in the Whitehall Study. Associations were assessed between mortality and Medical Research Council standardised questions about chronic phlegm production and breathlessness, and a measure of lung function. Low FEV1 was the most powerful single predictor of mortality; controlling for age, smoking habits and employment grade, the relative hazards ratio (RHR) was 20. Using mortality rates standardised for age and smoking, the proportion of mortality in the total population statistically attributable to low FEV1 (population excess fraction) was 57%. Breathlessness while walking on the level was the best predictor among the questions and combinations of questions; the relative hazards ratio was 12 and the population excess fraction, 39%. A Medical Research Council definition of chronic bronchitis including chronic phlegm production and breathlessness was also strongly associated with chronic bronchitis mortality (RHR = 13); however, the population excess fraction was only 20%. This definition identified only 30% of the 64 deaths, and added almost nothing to prediction by FEV1 alone. The results suggest that although the combination of chronic phlegm production and chronic airflow limitation is strongly associated with mortality from chronic bronchitis, the presence of chronic phlegm production alone is not associated with mortality. PMID- 2592907 TI - The use of hormonal replacement therapy and the risk of stroke and myocardial infarction in women. AB - STUDY OBJECTIVE: To determine whether there is an association between the use of hormonal replacement therapy (HRT) and the risk of stroke and myocardial infarction (MI). DESIGN: A case-control study of women with stroke or MI was undertaken. SETTING: The cases were notified from 83 general practices to the coordinating centre at Northwick Park Hospital, where the diagnoses were independently confirmed. SUBJECTS: The cases, 603 white women aged 45-69, were each matched to two controls for age and general practitioner. Of the controls, 79% were the first eligible, 15% the second eligible and 6% were obtained at the third or more attempt. MEASUREMENTS AND MAIN RESULTS: A research nurse completed a questionnaire for each case and both controls, which included information obtained from the medical notes on the prescriptions of HRT. An independent quality control check on the selection of controls and on the abstraction of information from the medical notes was made. More than one HRT prescription had been given to 109 cases (18%) and 174 controls (14%), showing a weak association between the risk of stroke and MI and the past use of HRT (relative risk [RR] 1.36, 95% confidence interval [CI] 1.01-1.81). There was a stronger association with preparations contained progestogen alone (RR 1.90, 95% CI 1.11-3.25). On average, HRT had been used 9 years before recruitment to the study and for 15 months. However, the observed gradients of risk according to the duration of HRT use and time since HRT use do not support a causal interpretation. Also, the estimated relative risks were reduced when allowance was made for other cardiovascular risk factors. CONCLUSIONS: There is no evidence that the use of HRT as recently prescribed in the UK constitutes a major cardiovascular risk or benefit. PMID- 2592908 TI - The characteristics of a national register of people with multiple sclerosis (MS): a comparison between the ARMS (Action for Research into Multiple Sclerosis) register and 10 British MS populations. AB - Problems with case ascertainment in epidemiological research on multiple sclerosis (MS) make it necessary to use indirect sources. However, there is a lack of information about the characteristics of cases drawn from different sources and thus little basis on which sampling frames for large scale surveys may be constructed. The characteristics of a population drawn from the membership of Action for Research into Multiple Sclerosis (ARMS) were compared with those of 10 other British MS populations reported between 1980 and 1987. Demographic variables examined were geographical location, nationality, ethnicity, sex ratio and age. Diagnostic status, age at diagnosis and duration since diagnosis were considered together with data on the comparative populations based on date of onset. On all the variables investigated the ARMS population fell close to or within the range shown by the comparative populations. The relative youth of the ARMS population and its bias towards a high proportion of females were differences in keeping with existing knowledge about the membership of mutual support organisations. A population drawn from such an organisation may usefully complement other MS research populations provided that the likely biases in each are understood. PMID- 2592909 TI - Apparent effect of immune serum globulin prophylaxis in the military on viral hepatitis incidence in the civilian population in Israel. AB - Since 1969, extensive use of immune serum globulin in the Israel Defence Force for prophylaxis against hepatitis A virus (HAV) infection has produced a sharp decline in the incidence of the disease. However, it is not clear whether this policy has affected the susceptibility of Israeli adults to HAV infection. In this study, we examined the effect of the immunisation policy on the incidence of hepatitis A virus infection in the civilian population in the 15-44 year age group, which includes all those who have completed compulsory military service since vaccination was introduced. The incidence of viral hepatitis in the Jewish civilian population aged 15-44 increased by approximately 50% 3-4 years after the implementation of the immunisation policy. This rise was not seen in the non Jewish population of the same age nor among Jews aged 45-64. These findings strongly suggest that the immunisation policy in the military prevents both clinical and sub-clinical disease, but has had the effect of producing more susceptible people at an older age in the civilian population. PMID- 2592910 TI - Relation between all cause standardised mortality ratios and two indices of deprivation at regional and district level in England. AB - The use of mortality data in the form of standardised mortality ratios (SMRs) to measure the need for health care resources in the Resource Allocation Working Party (RAWP) formula in England has been criticised for underestimating the wider effects of adverse socioeconomic conditions on need, particularly in inner city areas. To assess this criticism, we explored the relationships at NHS Regional and District levels in England between two indicators of illness from the 1981 Census, two contrasting indices of deprivation based on the 1981 Census (the Jarman 8 Underprivileged Area (UPA) score and Townsend's Index of Material Deprivation) and their constituent variables, and all cause SMRs for 1982-3. All cause SMRs were highly correlated at Regional and District level with permanent and temporary sickness rates. At Regional level, three of the Thames Regions showed relatively high deprivation scores in relation to their SMRs, in comparison to the remaining Regions where the relative level of deprivation closely matched the Region's mortality ranking. District level analyses of the relations between SMRs and the deprivation indices and their constituent variables showed that the Thames/non-Thames dichotomy was accounted for by the 14 Districts in inner London. These findings suggest that although there may be a prima facie case for including an allowance for deprivation in RAWP, it is still not clear how the deprivation variables available in the Census relate empirically to the need for additional health service resources. The analysis raises questions about the appropriate definition of need in this context and whether the Census is a suitable source for the construction of a deprivation weighting for use in national RAWP. PMID- 2592911 TI - The family physician and managed health care. PMID- 2592913 TI - Diagnosis of infectious mononucleosis. PMID- 2592912 TI - Gonococcal endocarditis. PMID- 2592914 TI - Obstetrics in family practice. PMID- 2592915 TI - Obstetrics in family practice. PMID- 2592916 TI - Genogram and family dynamics. PMID- 2592917 TI - Microcomputer-generated reminders. PMID- 2592918 TI - Obstetric privileges in family practice. PMID- 2592919 TI - Ethics and therapeutic skepticism. PMID- 2592920 TI - Prevalence of hepatitis B in an indigent, multi-ethnic community clinic prenatal population. AB - Perinatal infection of hepatitis B virus (HBV) from an infected asymptomatic woman to her offspring is now a preventable disease. A chart review was undertaken to document the prevalence of asymptomatic HBV infection in a high risk, predominantly minority, indigent, and immigrant family practice clinic population and to evaluate the frequency of accepted known risk factors for those subjects with positive hepatitis B surface antigen (HBsAg) screening tests. Records for 464 pregnant women entering the prenatal program between January 1, 1983, and April 30, 1987, were reviewed. Twenty-three (5.3%) were found positive for the HBsAG, all were asymptomatic. Results of a logistic regression on multiple risk factors for HBV infection revealed that ethnicity was the sole predictor of a positive HBsAg screening test, with 13% of the Asian patients and 1% of the Latino subjects positive for HBsAg. Other historical factors such as previous sexually transmitted disease and past history of transfusion were not predictive. These results reaffirm that a screening program for asymptomatic HBV infection in selected prenatal populations can identify a significant number of infants at risk for risk for perinatal infection. PMID- 2592921 TI - AIDS with disseminated histoplasmosis. AB - This report is a description of two Ohio cases of acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis, with discussion of diagnosis and treatment of this combination. The patient in case 1 developed disseminated histoplasmosis as the first significant symptomatic medical condition of his life. The patient in case 2 presented with severe pharyngitis, but without signs or symptoms specific to the lungs. Amphotericin B alone does not eradicate histoplasmosis in an AIDS patient. The best therapy at present is a full course of amphotericin B followed by a lifetime regimen of ketoconazole to prevent relapse. Family physicians in the District of Columbia, Texas, Maryland, Louisiana, Missouri, Illinois, Arizona, and Puerto Rico should be particularly vigilant in looking for the combination of these two diseases. PMID- 2592922 TI - Toilet training in first children. AB - Parents of 266 children were queried about the process they used to toilet train their first child. Results showed that they learned the training process most frequently from intuition, from their parents, and from friends with small children. Most children were put on the potty chair and were praised when successful. About three fourths of the parents responded that readiness of the child prompted initiation of toilet training. The largest number of children (42.6%) were 24 to 29 months old when training began and 30.5% were 18 to 23 months old. The mean ages for completion of training were between 24 and 27 months. PMID- 2592923 TI - House call practices among young family physicians. AB - Once a major part of medical practice, physician house calls have declined in frequency over the years. Recently, it has been suggested that house calls are increasing. This study examined the current self-reported house call practices among recent graduates of family practice residency programs in the United States. A questionnaire was mailed to a cross-sectional, random national sample of 301 family physicians who are members of the American Academy of Family Physicians and who completed a residency between 1981 and 1986. There was a 66% response rate to three mailings, with 197 questionnaires analyzed. Sixty-two percent of the physicians reported they were making house calls. The majority (53%) made less than one house call per month. Fewer than 15% made house calls on a weekly basis. There was a downward trend by residency year in the percentage of physicians making house calls when comparing graduates from 1981 to 1986. House calls do not appear to be a significant part of the practice of young family physicians. PMID- 2592924 TI - Chemistry--a scientific model for family medicine? AB - The academic basis of family medicine is currently undergoing reexamination. Some would have the specialty leave the academic arena and pursue a biopsychosocial mode of practice in the community. Others would have family medicine aggressively pursue academic research, apparently by abandoning the biopsychosocial approach to medical care. Chemistry as an academic discipline and as applied in community practice has solved many of the problems facing family medicine today. This paper suggests that one may learn much from chemistry. Four basic principles of applied science are presented from the point of view of a chemist: (1) science has an important but strictly limited contribution to make to medical practice; the humanistic goals of family medicine are philosophical decisions, and science is used to attain these goals; (2) observations are the basic reality of science; theory, to be useful, must explain and predict observations; (3) there is a basic unity in science; and (4) there is no hierarchy in scientific understanding. A model based on these four principles is presented that defines family medicine as the central, coordinating discipline in modern academic and community medical practice. PMID- 2592925 TI - Who goes into family medicine? AB - A study was designed to identify criteria that could help select applicants to medical school with a lasting commitment to family medicine and to test the application of such criteria to predict career choice. The sample included 43 residents and physicians who chose family medicine when they entered medical school and five residents who decided on family medicine later. From the initial group, 19 remained stable in their choice of family medicine, and 24 switched to another specialty. Medical school folders and telephone interviews were used as data sources. The characteristics of stable family physicians and those who became specialists were identified, and the predictive power of these criteria was tested with 30 graduates selected at random. Based only on their entrance records, 25 of the 30 graduates were correctly identified as future family physicians or specialists. The use of these criteria in the admission process is discussed in terms of increasing the number of students who will become stable family physicians. PMID- 2592926 TI - Hyperthyroidism after hypothyroidism. The broad spectrum of autoimmune thyroid disease. PMID- 2592927 TI - Gonorrhea presenting as a subcutaneous abscess. PMID- 2592928 TI - Accidental ingestion of oil of wintergreen. PMID- 2592930 TI - Why cost controls fail. PMID- 2592929 TI - Why physicians must not give food and water to every patient. PMID- 2592931 TI - Can the legal profession have a point? PMID- 2592932 TI - Glaucoma diagnosis and treatment. AB - The subject of glaucoma continues to be an increasing problem due to higher incidence in the elderly citizens of the United States. While glaucoma is a lifelong disease, it needs to be carefully monitored and understood not only by vision care specialists but also those in other health related fields such as internal medicine, family medicine, and certain medical subspecialties. This article is an overview of the glaucomas, their classifications, etiologies, and most common forms of therapy. Emphasis is placed on the need for the vision practitioner to work closely with other health related fields. PMID- 2592934 TI - The American way: get what you can through the political process. PMID- 2592933 TI - Advances in oculoplastic surgery. AB - Ophthalmic plastic surgery, a sub-specialty within ophthalmology, encompasses diagnosis and treatment of diseases and abnormalities of the eyelids, orbit, and lacrimal systems. Eyelid carcinoma is a more common entity as well as blepharoptosis seen in children and adults. It can usually be corrected by surgery involving the levator palpebrae superioris or a tarsofrontalis suspension using synthetic material or human tissue. Retraction of the upper eyelid, the opposite of blepharoptosis, may be seen in patients with thyroid eye (Graves') disease. Treatment by recession of the levator aponeurosis and Muller's sympathetic muscle yields excellent results. Blepharoplasty and other procedures frequently performed by the ophthalmic plastic surgeon can be done for cosmetic or functional (correction of vision) reasons and often in conjunction with other eyelid surgery such as ptosis repair. PMID- 2592935 TI - Starting a practice in the 1980s. PMID- 2592936 TI - Ophthalmology, the Academy and the future. PMID- 2592937 TI - Medical cost containment: will economic restrictions affect quality care and access? PMID- 2592938 TI - Effects of exercise and ticlopidine on platelet function and prostanoids in patients with old myocardial infarction. AB - Twenty-eight subjects, 16 with old myocardial infarction (OMI) and a control group of 12, received ticlopidine 250 mg/day for 4 weeks. All subjects underwent the standard Bruce protocol exercise test before and after therapy. Blood was collected from a peripheral vein to study platelet function at pre-exercise (rest), peak exercise (end point), and 6 min post-exercise (recovery). Platelet count, platelet aggregatory response, plasma thromboxane B2 (TXB2), and 6-keto PGF 1 alpha were measured by Coulter counter, aggregometry, and radioimmunoassay, respectively. The platelet count, aggregatory response (induced by ADP, adrenalin, and collagen) and the plasma concentration of TXB2 and 6-keto-PGF 1 alpha were not significantly affected by exercise in the OMI and control groups. Overall, there were no significant changes in exercise duration, heart rate, and blood pressure in both groups before or after ticlopidine treatment, with some minor exceptions. There were no significant changes in the peripheral blood profiles, the bleeding and coagulation times, the blood chemistry data, and the platelet counts between the groups before or after treatment. There was a significant decrease in collagen- and ADP-induced platelet aggregation in both groups after ticlopidine therapy. Prior to treatment, a higher plasma TXB2 concentration was noted in the OMI group during and after exercise; the difference was no longer statistically significant after ticlopidine therapy when both groups were compared. There was a significant reduction in the TXB2 levels in the OMI group after ticlopidine treatment despite exercise. Before therapy, plasma 6-keto-PGF 1 alpha was significantly elevated in the OMI group before or after exercise but was not statistically significant after ticlopidine treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592939 TI - Doppler echocardiographic findings in healthy Chinese adults. AB - To establish a norm for cardiac velocities in healthy Chinese adults, we examined 30 normal subjects (15 men and 15 women) with pulsed- and continuous-wave Doppler, and color flow mapping. The subjects ranged in age from 18 to 60 years (mean 37 years). We found that the early (E) and late (A) diastolic peak velocities for the mitral valve were 87 +/- 16 cm/sec and 61 +/- 15 cm/sec, respectively. The E/A ratio was 1.5 +/- 0.4. The E and A peak velocities for the tricuspid valve were 57 +/- 10 cm/sec and 40 +/- 7 cm/sec, respectively. The peak velocities for the left ventricular outflow tract, the ascending aorta, the proximal descending aorta and the main pulmonary artery were 77 +/- 19, 106 +/- 20, 96 +/- 24 and 74 +/- 17 cm/sec, respectively. None of the velocities exceeded 154 cm/sec. There were no significant differences between men and women. However, older subjects (greater than or equal to 40 years) had a higher mitral A velocity (69 +/- 13 cm/sec vs 57 +/- 17 cm/sec, p less than 0.05) and a lower E/A ratio (1.3 +/- 0.4 vs 1.6 +/- 0.3, p less than 0.05) than did subjects under 40 years of age. Mild tricuspid regurgitation was detected in 8 of the 30 subjects (27%), mitral regurgitation in 3 of the subjects (10%) and pulmonic regurgitation in one of the subjects (3%). There was no aortic regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2592940 TI - Short- and long-latency median nerve somatosensory evoked potentials in stroke patients. AB - Short- and long-latency somatosensory evoked potentials (SEPs) were elicited by stimulation of the median nerve in 104 stroke patients, 59 men and 45 women. Their ages ranged from 25 to 90 years, with a mean age of 68 years. All of the patients presented with acute unilateral motosensory or sensory deficits. Based on CT findings, the patients were divided into four groups: thalamic hemorrhage (52 cases), thalamic infarct (21 cases), putaminal hemorrhage or infarct (13 cases) and infarction in the corona radiata or subcortical white matter (18 cases). The criteria for abnormal SEP responses were as follows: (1) absence of N18, (2) prolongation of central conduction time, (3) delay in peak latency of N32, (4) delay in peak latency of N60, and (5) decrease in response amplitude. In patients with thalamic stroke, the abnormality rate of SEPs was 93% (68 out of 73 cases). When the lesions were located primarily in the posterolateral thalamus, all SEP components, particularly the N18 (short-latency) component, were affected. Lesions in other thalamic areas caused changes in the N32 (mid-latency) and the N60 (long-latency) components. In putaminal, corona radiata and subcortical lesions, the abnormality rate of SEPs was 84% (26 out of 31 cases). The N18 component was absent in 3 patients with putaminal hemorrhage. Infarct in the corona radiata and subcortex tended to affect the mid- and long-latency components with relative preservation of the short-latency components. PMID- 2592941 TI - Endoscopic sphincterotomy in the treatment of biliary tract diseases. AB - Endoscopic sphincterotomy (EST) was performed in 53 patients with biliary disease. Indications for sphincterotomy were: 48 patients with choledocholithiasis, 3 patients with malignant biliary obstruction, and 2 patients with papillary stenosis. The procedure was successful in 52 patients (98.1%). In patients with choledocholithiasis, the stones were successfully removed or passed out spontaneously in 42 patients (87.5%). Endoscopic retrograde biliary drainage (ERBD) was successfully carried out in 2 cases of malignant biliary obstruction after EST. The clinical and biochemical evidence of cholestasis resolved in both patients with papillary stenosis. Complications consisted of hemorrhage (2 patients) and cholangitis (1 patient), resulting in one death. The overall complication and mortality rates were 5.7% and 1.9% respectively. Thirty-two patients received regular ultrasound examination follow up with a mean of 13.4 months. Two patients had recurrent common bile duct stones and one had restenosis of papilla. The conditions were managed by endoscopic therapy. Endoscopic sphincterotomy is a relatively safe and effective means of relieving extrahepatic cholestasis; however, its comparison with surgical techniques needs long-term, randomized studies. PMID- 2592942 TI - Tumor markers of lung cancer: carcinoembryonic antigen and TuMark. AB - To assess the value of tumor marker determinations in diagnosing lung cancer and monitoring the response to therapy in lung cancer patients, we tested the serum concentration of TuMark-reactive protein and carcinoembryonic antigen (CEA) in 78 patients with lung cancer and 81 patients with non-malignant diseases. The sensitivity of TuMark in detecting the presence of lung cancer was 63.8%, compared to 37.2% for CEA (p less than 0.05). The specificity was 91.3% for TuMark and 97.5% for CEA. The combination of TuMark and CEA increased the sensitivity to 74.3%. The sensitivity of TuMark for non-small cell carcinoma was significantly higher than that for small cell carcinoma (67.6% vs 30.0%) (p less than 0.05). The incidence of positive TuMark reactivity did not correlate with the stages of lung cancer. Since the incidence of positive CEA reactivity was lower in the limited stage than in the extensive stage of lung cancer (20.0% vs 43.1%), the sensitivity of TuMark with regard to the detection of early stage lung cancer appeared far superior to CEA (65.0% vs 20.0%, p less than 0.05). Serial monitoring of TuMark levels in 32 patients with all types of lung cancer showed that 84% correlated with their clinical courses. Six patients with stage I or II disease received complete surgical resection of tumors. All showed a decline of the TuMark level to normal levels in 17 to 48 days (average of 32 days). These results suggested that the TuMark test may be a useful new marker for diagnosing lung cancer and monitoring response to therapy, especially for non small cell lung cancer. PMID- 2592943 TI - Serum squamous cell carcinoma antigen in gynecologic malignancies with special reference to cervical cancer. AB - Squamous cell carcinoma (SCC) antigen was measured by double-antibody radioimmunoassay in the sera of 113 patients with gynecologic malignancies and 30 controls. The mean serum SCC antigen level was 9.24 ng/ml in those with cervical squamous cell carcinoma, 2.15 ng/ml in those with other gynecologic malignancies, and 1.25 ng/ml in controls. With a cutoff value of 2.23 ng/ml (2 SD above the mean of the control group), the rate of SCC antigen elevation was 54% in cervical cancer (78), 14% in vulvar or vaginal cancer (7), 22% in ovarian cancer (18), and 10% in endometrial cancer (10). In cervical squamous cell carcinoma, the rates of elevated SCC antigen level increased with disease advancement in stages 0, I, II, III, and IV, by 13, 50, 53, 78, and 100%, respectively. In early-stage cervical squamous cell carcinoma, SCC antigen was not sensitive enough for screening. However, if elevated, serum SCC antigen levels decreased rapidly after successful surgical treatment. One case with a serum SCC antigen level above 65 multiples of the cutoff value had widespread cancer and postoperative recurrence. In the advanced case, the sensitivity was much higher. In the recurrent case, the positive rate was 73%. Serum SCC antigen level is useful in predicting the prognosis and monitoring the course of cervical squamous cell carcinoma, especially in the detection of a recurrence. PMID- 2592944 TI - Application of nasopharyngoscopy and videofluoroscopy in the fabrication of a speech aid for soft palate defects. AB - Conventional methods of speech aid fabrication have little control over the pharyngeal extension or over the adequacy of the velopharyngeal closure. These limitations can be overcome by using a nasopharyngoscope, which provides the operator with direct vision during the molding of the pharyngeal section. Likewise, the use of a videofluoroscope also permits visualization of the prosthesis in relation to the surrounding structures during various activities, and is equally valuable in the evaluation of the velopharyngeal mechanism. In both instances, the evidence of inadequate closure could be seen as mucus bubbling or refluxing of barium from the junction of the prosthesis with the soft palate defect. Also the standard Mandarin phrases used in the speech test and the advantages of nasal endoscopy over oral endoscopy are discussed. PMID- 2592945 TI - Extrahepatic biliary obstruction caused by cancer of non-liver origin in children: report of 5 cases. AB - Obstructive jaundice secondary to external compression of the extrahepatic bile duct caused by tumor of non-liver origin was found in 5 of 199 consecutive children with cancer between 1986 and 1988 at the Department of Pediatrics, National Taiwan University Hospital. Of the 5 patients, 2 had non-Hodgkin's lymphoma and the other 3 had acute promyelocytic leukemia, histiocytosis X and neuroblastoma, respectively. Extrahepatic biliary obstruction occurred as part of the initial presentation of malignancy in 3 cases, and later in the course of disease in the other 2 cases. In each instance, abdominal ultrasonography and computed tomography revealed dilatation of intrahepatic biliary trees due to mass compressing effects. A huge multilobulated tumor and multiple enlarged lymph nodes near the porta hepatis were found in all 3 patients who underwent an exploratory laparotomy. Wedge biopsy of the liver showed no cancer cell invasion. One case died before chemotherapy had commenced. The other 4 patients received chemotherapy and 3 of them received additional radiotherapy. Although jaundice and tumor regressed dramatically with this mode of treatments, subsequent recurrence of tumor without jaundice rapidly ensued in 3 patients. They all died, except 1 case, within 18 months from the occurrence of jaundice. This suggests that these patients were in an advanced stage of disease and should be diagnosed early and treated vigorously. Accordingly, cancer of non-liver origin, although rare, should be considered in the differential diagnosis of obstructive jaundice if survival is to be improved in these cancer children. PMID- 2592946 TI - Syndrome of hemolysis, elevated liver enzymes, and low platelet count: report of 4 cases. AB - Four cases of severe preeclamptic patients with the findings of hemolysis (H), elevated liver enzymes (EL) and a low platelet count (LP) were presented. Maternal mortality occurred in two of the four cases with one experiencing liver rupture. Intrauterine fetal death occurred in 3 cases. The entity has been termed the HELLP syndrome. The high maternal and perinatal mortality of our cases was mainly due to the severe coagulopathy associated with the HELLP syndrome. The practicing obstetrician must be knowledgeable about this severe consequence of toxemia in pregnancy and aggressive management is essential to improve maternal and perinatal outcome. PMID- 2592947 TI - Neonatal lupus erythematosus: report of a case. AB - We present the first report of neonatal lupus erythematosus from Taiwan. A female baby, born to a mother with documented systemic lupus erythematosus (SLE), developed cutaneous lupus lesions after phototherapy for hyperbilirubinemia. She had additional clinical features of hemolytic anemia and thrombocytopenia. Detailed serological and immunogenetic studies were performed. Transplacental passage of both anti-SSA/Ro and anti-SSB/La antibodies were demonstrated and their disappearance at the age of 6 months correlated with regression of clinical symptoms. This patient inherited human leukocyte antigen (HLA) A11, Bw60 Cw3, DR2 and Aw33, Bw57, Cw7, DRw6 from her father and mother, respectively. A long-term follow-up is required for observing whether she will develop SLE in the future. PMID- 2592948 TI - [The diagnostic value of radionuclide inferior veno-cavagraphy in Budd-Chiari syndrome]. AB - To evaluate the diagnostic value of radionuclide inferior veno-cavagraphy (RIVC) for Budd-Chiari Syndrome, RIVC using Tc99m was performed on 106 patients with massive ascites. A positive RIVC result was defined as having at least two of the three following criteria: (1) a delay of more than 4 seconds in visualizing the heart; (2) sharply truncated inferior vena cava with marked hang-up of isotope activity; and (3) extensive collateral circulation. Of the 106 patients, 18 were RIVC positive and were later confirmed by operation or contrast venography to have Budd-Chiari Syndrome with IVC obstruction. Of the remaining 88 RIVC negative patients, 3 were shown by operation, computerized tomography and cardiac echo, respectively, to be Budd-Chiari Syndrome with IVC obstruction. Thus, the diagnostic sensitivity and specificity of RIVC for this syndrome was 85.7% and 100% respectively. If RIVC is combined with hepatic scintigraphy, it will help to elucidate the anatomic and functional change of IVC, as well as, liver parenchymal disease, such as liver cirrhosis, hepatic tumor or hepatic vein obstruction. RIVC is a simple safe, accurate, noninvasive and reproducible procedure. This study confirms the high diagnostic specificity and sensitivity of RIVC. We therefore recommend RIVC as the first-line study for IVC patency. Contrast venography may be used as a confirmatory study in preparation for surgical intervention. PMID- 2592949 TI - [Colpocephaly: report of a case]. AB - A 43-year-old G12P4 mother delivered, at 35 weeks of gestation, a girl with a birth weight of 1980 g. Since her last pregnancy 20 years ago, she had had 8 subsequent abortions. Amniocentesis was done at the 18th week of gestation and revealed negative findings. Because of maternal age, the baby was delivered by cesarean section. The family history was not pertinent. After birth, the baby was noted to have a large head girth (34.5 cm) with widened anterior fontanel and mild frontal protrusion. The neurosonography showed symmetric dilatation of the frontal horns and temporal horns of the lateral ventricles, hyperechodensity in the periventricular wall, absence of corpus callosum and cavum septum pellucidum, and a large communicating pear-shaped ventricular cavity on the posterior coronal view. The brain CT scan demonstrated evidence of extreme dilatation of the occipital horns of the lateral ventricles and prominence of the subarachnoid spaces in the supra-Sylvian fissures. Based on these findings, the baby was diagnosed as a case of colpocephaly. Patients with colpocephaly usually have moderate to severe mental retardation, motor deficits, visual abnormalities and seizures. They need speech and physical therapies as early as possible. Therefore, if early diagnosis is confirmed by fetal sonography before the 5th month of gestation, this congenital brain malformation can be prevented by therapeutic abortion. PMID- 2592950 TI - [Sarcoidosis with ocular involvement]. AB - A 28-year-old Chinese woman having sarcoidosis with ocular involvement was reported. She demonstrated bilateral hilar lymphadenopathy in a chest X-ray which was taken for a cough. Transbronchial lung biopsy revealed noncaseating epithelioid granulomas. Blurred vision occurred 8 months later when conjunctival follicle-like masses, granulomatous keratic precipitates, iridocyclitis, "snow ball" vitreous opacity, and retinal periphlebitis developed in both eyes. Biopsy of the conjunctival follicle-like masses revealed noncaseating granulomas composed of epithelioid cells and multinuclear giant cells, typical of sarcoidosis. The ocular lesions waned under topical steroid treatment and vision improved. This is the only case with an ocular involvement among the 10 cases of sarcoidosis seen during the past 20 years at the Taipei Veterans General Hospital. PMID- 2592951 TI - The Ca2+-activated K+ channel and its functional roles in smooth muscle cells of guinea pig taenia coli. AB - Currents through single potassium channels were studied in cell-attached or inside-out patches from collagenase-dispersed smooth muscle cells of the guinea pig taenia coli. Under conditions mimicking the physiological state with [K+]i = 135 mM: [K+]o = 5.4 mM, three distinct types of K+ channel were identified with conductances around 0 mV of 147, 94, and 63 pS. The activities of the 94- and 63 pS channel were observed infrequently. The 147-pS channel was most abundant. It has a reversal potential of approximately -75 mV. It is sensitive to [Ca2+]i and to membrane potential. At -30 mV, the probability of a channel being open is at a minimum. At more positive voltages, the probability follows Boltzman distribution. A 10-fold change in [Ca2+]i causes a 25-mV negative shift of the voltage where half of the channels are open; an 11.3-mV change in membrane potential produces an e-fold increase in the probability of the channel being open when P is low. At voltages between -30 and -50 mV, the open probability increases in an anomalous manner because of a large decrease of the channel closed time without much change in the channel open time. This anomalous activity may play a regulatory role in maintaining the resting potential. The histograms of channel open and closed time fit well, respectively, with single and double exponential distributions. Upon step depolarizations by 100-ms pulses, the 147-pS channel opens with a brief delay. The delay shortens and both the number of open channels and the open time increase with increasing positivity of the potential. The averaged currents during the step depolarizations closely resemble the delayed rectifying outward K+ currents in whole-cell recordings. PMID- 2592954 TI - Artifact in the hypnosis-creativity relationship. AB - Subjects who pretested high or low in hypnotic suggestibility took a creativity test either under hypnosis or in a waking state. All subjects made a global estimate of their general degree of creativity. Greater figural-spatial creativity was exhibited in the hypnosis condition than in the waking condition by both high and low suggestibles. Creativity self-reports were not corroborated by actual creative performance. PMID- 2592952 TI - Permeation, selectivity, and blockade of the Ca2+-activated potassium channel of the guinea pig taenia coli myocyte. AB - The permeation properties of the 147-pS Ca2+-activated K+ channel of the taenia coli myocytes are similar to those of the delayed rectifier channel in other excitable membranes. It has a selectivity sequence of K+ 1.0 greater than Rb+ 0.65 greater than NH4+ 0.50. Na+, Cs+, Li+, and TEA+ (tetraethylammonium) are impermeant. Internal Na+ blocks K+ channel in a strongly voltage-dependent manner with an equivalent valence (zd) of 1.20. Blockade by internal Cs+ and TEA+ is less voltage dependent, with d of 0.61 and 0.13, and half-blockage concentrations of 88 and 31 mM, respectively. External TEA+ is about 100 times more effective in blocking the K+ channel. All these findings suggest that the 147-pS Ca2+ activated K+ channel in the taenia myocytes, which functions physiologically like the delayed rectifier, is the single-channel basis of the repolarizing current in an action potential. PMID- 2592953 TI - Inactivation of A currents and A channels on rat nodose neurons in culture. AB - Cultured sensory neurons from nodose ganglia were investigated with whole-cell patch-clamp techniques and single-channel recordings to characterize the A current. Membrane depolarization from -40 mV holding potential activated the delayed rectifier current (IK) at potentials positive to -30 mV; this current had a sigmoidal time course and showed little or no inactivation. In most neurons, the A current was completely inactivated at the -40 mV holding potential and required hyperpolarization to remove the inactivation; the A current was isolated by subtracting the IK evoked by depolarizations from -40 mV from the total outward current evoked by depolarizations from -90 mV. The decay of the A current on several neurons had complex kinetics and was fit by the sum of three exponentials whose time constants were 10-40 ms, 100-350 ms, and 1-3 s. At the single-channel level we found that one class of channel underlies the A current. The conductance of A channels varied with the square root of the external K concentration: it was 22 pS when exposed to 5.4 mM K externally, the increased to 40 pS when exposed to 140 mM K externally. A channels activated rapidly upon depolarization and the latency to first opening decreased with depolarization. The open time distributions followed a single exponential and the mean open time increased with depolarization. A channels inactivate in three different modes: some A channels inactivated with little reopening and gave rise to ensemble averages that decayed in 10-40 ms; other A channels opened and closed three to four times before inactivating and gave rise to ensemble averages that decayed in 100-350 ms; still other A channels opened and closed several hundred times and required seconds to inactivate. Channels gating in all three modes contributed to the macroscopic A current from the whole cell, but their relative contribution differed among neurons. In addition, A channels could go directly from the closed, or resting, state to the inactivated state without opening, and the probability for channels inactivating in this way was greater at less depolarized voltages. In addition, a few A channels appeared to go reversibly from a mode where inactivation occurred rapidly to a slow mode of inactivation. PMID- 2592955 TI - Hypnotic susceptibility and familial handedness. AB - The possible relationship between hypnotic susceptibility and familiar handedness was examined. In a mass-testing session of students enrolled in introductory psychology classes, subjects were administered the Harvard Group Scale of Hypnotic Susceptibility, Form A and were also required to complete a questionnaire that ascertained information on their dominant handedness and that of their immediate family relatives. Subjects who had immediate sinistral relatives scored significantly lower in hypnotic susceptibility compared to those who had a history of familial dextrality. When immediate relatives of the original subject pool were tested on hypnotic susceptibility level, sinistral relatives scored lower in susceptibility than dextral relatives. This may indicate the existence of a familial component in hypnotic susceptibility. PMID- 2592956 TI - Improving cognitive search skills in resistant hypnotic subjects. AB - Subjects who were resistant (n = 20) and susceptible (n = 20) to hypnotic suggestion were asked to find the letter Z in an array of other straight-form letters. Susceptibles found the letter more quickly than resistants, and this superiority appeared to be related to their use of a more efficient search strategy. When resistants were taught this strategy, their performance was not significantly different from that of susceptibles. Implications of these results for teaching search strategies are discussed. PMID- 2592957 TI - Acoustic interference in a recognition task. AB - Phonetic or acoustic characteristics of stimuli in recall studies have consistently been shown to generate more interference over short intervals than semantic characteristics. We performed three experiments to determine whether this characteristic also applied to recognition processes over short intervals. Subjects were shown study lists of eight words and were asked to recognize which of those words recurred on subsequent eight-word lists. Delays varied from 0 to 100 s between study and test, with a rehearsal-preventing task inserted during the delays. Phonetic distractors generated greater interference than semantic distractors at all delay levels, and semantic distractors generated greater interference than random distractors. These distractor-type differences were not present in long-term recognition tasks. The deterioration in performance over time was considerably slower in these recognition experiments than in previous recall studies. PMID- 2592958 TI - Retrieval and comparison processes in part--whole decisions. AB - Undergraduate students were presented with word pairs (e.g., egg-yolk) and were timed as they decided whether one word named part of the thing named by the other word. In Experiment 1, "no" responses to nonpart pairs (e.g., fish-flaps) were slowed by the similarity of the stimulus part (flaps) to a part that the stimulus object did possess (fins). This suggested that decisions were made by retrieving parts of the stimulus object from memory and comparing them to the stimulus part. Whereas the parts used as stimuli in Experiment 1 were nonspecific, belonging to several different types of object (e.g., wheel), those selected for Experiment 2 were specific to a single type of object (e.g., thumb). In Experiment 2, "no" responses to nonpart pairs (e.g., foot-thumb) were slowed by similarity of the stimulus object (foot) to an object that the stimulus part (thumb) belonged to (hand). This suggested that decisions were made by retrieving the object to which the stimulus part belonged and comparing it to the stimulus object. The results support a hybrid model of part-whole decisions that includes directed retrieval of relational knowledge from memory and a comparison process. PMID- 2592959 TI - The relationship of daily hassles, social support, and coping to depression in black and white students. AB - Black and White American college students were compared to determine how daily hassles, coping strategies, and social support related to depression. Although the mean intensity of hassles did not differ, Black students reported a higher frequency of hassles. Cumulative severity of hassles, defined in terms of both intensity and frequency was therefore higher for Black students. White students perceived more support from friends than from family, but the opposite held for Black students. Mean scores on type of coping (active problem solving, seeking social support, or avoidance) were similar, as were the reported levels of depression. Hierarchical multiple regression showed that the severity of hassles was directly related to depression for both groups. Race did not interact with any index of social support, except perceived family support, which was related to lower depression among Black students. There was no support for the notion that social support serves as a buffer against depression. PMID- 2592960 TI - Cognitive therapy of panic disorder. A nonpharmacological alternative. AB - A naturalistic study with no predetermined duration of treatment was undertaken in order to examine the effectiveness of cognitive therapy in the treatment of panic disorder. Seventeen patients diagnosed as having panic disorder according to the Structured Clinical Interview for DSM-III Personality Disorders received a mean of 18 individual cognitive therapy sessions. Patients with personality disorder or depression required a longer duration of treatment to become symptom free. As measured by a self-report weekly panic log, the mean number of panic attacks was reduced significantly to zero at the end of treatment. There was a concomitant reduction in self-report measures of depression and anxiety. Further, there was a significant reduction on a measure of cognitive dysfunction during panic attacks. Treatment results were maintained at 12-month follow-up. PMID- 2592961 TI - Cognitive abnormalities in schizophrenic patients and schizotypal college students. AB - Twenty schizotypal college students, identified by the MMPI-168, were compared with 127 institutionalized or postinstitutional psychiatric patients with chronic schizophrenia, 140 normal control subjects, and 19 students with nonschizotypal MMPI elevations. The comparison measures were indices of cognition derived from COGLAB, a multiparadigmatic cognitive test battery. COGLAB includes measures of preattentional, attentional, conceptual, and psychomotor performance. As expected, the patients were deficient on all but one of the measures. The nonschizotypic elevation group was not different from the normal control group. Schizotypal subjects were found to have deficits in three areas of information processing: preattentional processing, response biasing, and concept attainment and manipulation. However, their performance was just as good as and less variable than that of normal subjects on psychomotor and attentional tasks. The results do not support the hypothesis that schizotypy is characterized by pervasive cognitive deficits which are simply less severe than those of other psychiatric groups. Rather, there are discrete deficits in specific areas and possibly compensatory abnormalities associated with primary deficits. The results are further discussed with regard to the hypothesis that schizotypy shares a common neurophysiological and/or developmental substrate with more severe psychiatric disorders. PMID- 2592962 TI - Thought disorder or allusive thinking in the relatives of schizophrenics? A response to Callahan, Madsen, Saccuzzo, and Romney. AB - Romney and Saccuzzo et al. (J Nerv Ment Dis 176:364-367; 368-371, 1988) disagreed concerning the need for further studies investigating the presence of thought disorder and associative cognitive dysfunction in relatives of schizophrenics. Saccuzzo et al. were concerned at the variations in the results of previous studies. Methodological issues relevant to such variation are discussed. It is pointed out that the study (McConaghy J Neurol Neurosurg Psychiatry 22:243-246, 1959) initiating psychometric investigation of cognitive processes of relatives of schizophrenics was based on the belief that what was familially transmitted was not thought disorder, but a nonpathological looseness of associations, shown also by a percentage of normal subjects. This looseness was later termed allusive thinking. It was considered that allusive thinking acted as an inherited predisposition to schizophrenia. It required the addition of impairment of abstract thinking to constitute the characteristic thought disorder originally described by Bleuler. To account for the significant degree of thought disorder found in 6% to 12% of normal subjects, some researchers now accept that thought disorder exists in normal subjects on a continuum with schizophrenic thought disorder. It is suggested that replication of a later study demonstrating familial transmission of allusive thinking in university students and their parents could aid in clarifying the significance of the findings of increased incidence of looseness of associations in the families of schizophrenics. PMID- 2592963 TI - A test of the therapeutic mechanism in social skills training with avoidant personality disorder. AB - Twenty-eight patients meeting the criteria for DSM-III avoidant personality disorder were randomly assigned to two treatment groups consisting each of five sessions of social skills training plus homework and five sessions of group discussion plus homework administered in different order in accordance with a latin-square (crossover) design. Twenty-one subjects completed the study. No significant differences between the treatment groups or treatment modalities (i.e., social skills training and group discussion combined with homework each) were found. Significant improvements in time on most measures were found when data from both groups were amalgamated. PMID- 2592964 TI - Personality and response to tricyclic antidepressants in depressed patients. AB - Several studies have shown that disturbances of personality are poor predictors of response to antidepressants. None of these studies, however, has used personality measures similar to the DSM-III. We evaluated the relationship between antidepressant response and personality scores obtained on the Millon Clinical Multiaxial Inventory, which provides personality measures congruent with DSM-III. Personality features such as assertiveness, independence, and competitiveness distinguished responders from nonresponders. However, the frequency of personality disorder diagnoses did not differ between responders and nonresponders. PMID- 2592965 TI - Intellectual impairment and cognitive evoked potentials in myotonic dystrophy. AB - Twenty-seven patients with myotonic dystrophy (MD) and 20 control subjects were tested using neuropsychological and electrophysiological measures. MD patients reported significantly lower scores on the Wechsler Adult Intelligence Scale and the Mini-Mental State Examination. P3 amplitude of auditory event-related potentials was significantly reduced in 14 patients. P3 latency was normal. In 13 patients, P3 was not elicited. Our results clearly show the presence of a significant impairment of cognitive functioning, as assessed by psychometric measures, in more than 50% of MD patients. Discriminant function correctly classified 92% of patients, using event-related potentials and neuropsychological variables. PMID- 2592966 TI - Magnetic resonance imaging in dementia of Parkinson's disease. AB - The possibility that dementia in Parkinson's disease is associated with specific cerebral abnormalities identifiable by magnetic resonance imaging (MRI) was examined. Sixty eight patients with Parkinson's disease and 28 age and education matched normal controls were evaluated using neuropsychological procedures that included assessment of language, memory, cognition, visuospatial skills and mood. Twenty three patients (34%) were found to have developed significant impairment in at least three of the five areas, thus meeting criteria for a dementia syndrome. Eleven patients (16%) had no intellectual impairment and thirty four patients (50%) had a mild to moderate intellectual disturbance. Patients with (n = 10) and without dementia (n = 20), matched for severity of Parkinson's disease, and normal controls (n = 10) matched for age with the two patients groups, were evaluated by MRI. MRI scans were analysed for evidence of generalised cerebral atrophy, ventricular enlargement, visualisation of the substantia nigra and severity of focal brain lesions. Results indicated that the presence of dementia in patients with Parkinson's disease was not associated with any specific pattern of MRI abnormalities. PMID- 2592967 TI - Visuospatial working memory in Parkinson's disease. AB - Visuospatial impairment is frequently reported in Parkinson's disease but the psychological mechanisms which subserve the impaired abilities and the way in which breakdown of the mechanisms leads to performance deficits have not been precisely delineated. This paper reports experimental investigations designed to test the hypothesis that the locus of the impairment is the visuospatial subsystem of working memory. Subjects were a group of sixteen patients with Parkinson's disease of mild to moderate severity and a matched control group. They performed complex visuospatial and verbal memory tasks. The Parkinsonian group were significantly slower than the control group when performing the visuospatial task. They were not significantly slower and made no more errors than the control group on the verbal task. The findings are compatible with the hypothesis that the visuospatial subsystem of working memory is impaired in Parkinson's disease. It is demonstrated that the impairment is not the result of a reduction in the capacity of this subsystem but is due to difficulty in utilising information stored in the subsystem to perform complex visuospatial tasks. PMID- 2592968 TI - Unilateral visual neglect overcome by cues implicit in stimulus arrays. AB - The case of a man with a right hemisphere lesion and with evidence of left-sided visuospatial neglect is reported. On a variety of verbal and nonverbal tasks his performance was significantly modified by information implicit in stimulus configurations. Neglect deficits were present on tests involving spatially distinct or meaningless stimulus arrays but almost absent when stimuli were continuous or meaningfully integrated. PMID- 2592969 TI - Arm function after stroke. An evaluation of grip strength as a measure of recovery and a prognostic indicator. AB - The value of strength of voluntary grip as an indicator of recovery of arm function was assessed by testing 38 recent stroke patients using a sensitive electronic dynamometer, and comparing the results with those from five other arm movement and function tests (Motricity Index, Motor Club Assessment, Nine Hole Peg Test, and Frenchay Arm Test). This procedure allowed measurement of grip in a large proportion of patients, and strength correlated highly with performance on the other tests. Measuring grip over a six month follow up period was a sensitive method of charting intrinsic neurological recovery. The presence of voluntary grip at one month indicates that there will be some functional recovery at six months. PMID- 2592970 TI - Familial distal dysautonomia. AB - A patient is described who presented with painful feet on exercise. He had no evidence of peripheral vascular disease but did have anhidrosis and failure of vasodilatation in the hands and feet suggesting peripheral dysautonomia. Examination of his mother and a cousin and clinical histories of blood relatives suggested that his problem was a severe presentation of a familial distal dysautonomia. In other family members this was represented by dry hands and feet and variable vasomotor symptoms. This condition appeared to be autosomal dominant. PMID- 2592971 TI - Idiopathic granulomatous meningitis. AB - A 69 year old female presented with eight discrete episodes of paraparesis over a period of six weeks. Each episode lasted between 10 and 30 minutes and resolved spontaneously. The cause of her symptoms was not established during life and at necropsy she was found to have granulomatous meningitis of the cerebral convexites. The clinical and pathological aspects of this rare condition are discussed. PMID- 2592972 TI - Clinicopathological correlation in a case of painful ophthalmoplegia: Tolosa-Hunt syndrome. AB - A case of painful ophthalmoplegia due to idiopathic granulomatous involvement of the superior orbital fissure (Tolosa-Hunt syndrome) is described. The clinical features of recurrent pain, ocular motor nerve palsies and proptosis correlated well with the eventual demonstration of an enhancing mass in the region of the cavernous sinus. Removal of the lesion led to a resolution of the clinical picture and demonstration of a non-caseating granuloma with no other detectable cause. The original observation of Tolosa was thus re-affirmed. PMID- 2592974 TI - Two techniques for the assessment of line bisection in visuo-spatial neglect: a single case study. AB - A patient with severe left neglect after surgery for basilar aneurysm is described. Her performance on freehand line bisection was compared and contrasted with the results from computerised visual display unit (VDU) presentation. In the latter format the patient makes her transections with a "mouse" controlled cursor arrow. The technique provides rigorous control over starting position and also allows self-corrections. Although left neglect persisted at longer line lengths under these conditions, the magnitude of the effect decreased significantly; the cross-over point where right displacements change to left displacements as a function of line length also varied between the three conditions (freehand, left and right computer-start). PMID- 2592973 TI - Chronic encapsulated intracerebral haematoma: pathogenetic and diagnostic considerations. AB - Two cases of chronic encapsulated intracerebral haematoma are reported. The patients presented with progressive neurological deficits. Computed tomography scan showed a roundish, intracerebral lesion, that revealed ring blush after contrast infusion, with mass effect. At operation a thick, fibrous, brownish capsule, containing clots in different states of formation, was removed. The hypothesis of capsule formation due to an exuberant proliferation of arachnoidal fibroblasts, is discussed. Differentiation between encapsulated intracerebral haematoma and other chronic intracerebral blood collections is considered mandatory for appropriate treatment. PMID- 2592975 TI - Singing in the brain: a new form of complex partial seizure? PMID- 2592976 TI - Intradural spinal lipoma with enlarged intervertebral foramen. PMID- 2592977 TI - Overestimated disease duration. PMID- 2592978 TI - Prognosis in stroke. PMID- 2592979 TI - Immunochemical study of connectin (titin) in neuromuscular diseases using a monoclonal antibody: connectin is degraded extensively in Duchenne muscular dystrophy. AB - Connectin (also called titin) is a myofibrillar elastic filament which links a thick filament to a neighbouring Z line in a sarcomere and thus contributes significantly to the elastic property of myofibrils. In the present study, the degradation state of connectin in biopsied skeletal muscles from various neuromuscular diseases was investigated by Western blot analysis using a monoclonal antibody which reacts extensively with the degradation products of connectin. In Duchenne muscular dystrophy (DMD), connectin was degraded progressively and relentlessly after 5 years of age. In Becker muscular dystrophy, degradation of connectin was much less than in DMD. Connectin was well preserved in normal controls, and was only minimally degraded in Charcot-Marie Tooth disease, amyotrophic lateral sclerosis, limb girdle muscular dystrophy and myotonic dystrophy, even when the biopsied muscles showed a similar degree of weakness as those of DMD. The degradation of connectin, even though secondary, is presumed to play an important role in the pathogenesis of myofibrillar degeneration in DMD. PMID- 2592980 TI - Aluminum affects interconnections between aggregates of cultured hippocampal neurons. Neurotoxicity of aluminum in vitro. AB - The effect of aluminum (Al) was studied in an in vitro system of cultured hippocampal neurons from fetal rats in a chemically defined medium. Neuronal aggregates interconnected by neurites were detected light and electron microscopically in control and Al-treated cultures. In the Al-treated cultures disruptions of the fibers were observed proximal to the aggregates; the number of disruptions increased with The Al concentration applied. It is concluded that interference of intracellular Al with the neuronal skeleton occurs, leading to an enhanced fragility of the interconnecting neurites. The concentration-dependent Al-induced disruption of interconnecting neurites may serve as an in vitro model for further research in Al neurotoxicity. PMID- 2592981 TI - Vibration perception and thermoperception as quantitative measurements in the monitoring of cisplatin induced neurotoxicity. AB - In 20 ovarian cancer patients treated by cisplatin-based chemotherapy quantitative investigations of the vibration and the thermoperception were performed. Following the administration of cisplatin of 300 mg/m2 and more the vibration perception threshold (VPT) was shown to be significantly elevated in all patients, despite the absence of clinical symptoms and signs in a number of patients. The VPT returned within 8 months to its original level in the 2 patients who were followed after cessation of therapy (cumulative dose of cisplatin 450-525 mg/m2). The changes seen in hands and in feet were comparable. There was no significant difference between the left and the right hand side. Thermoperception thresholds did not change during the treatment period. This study shows that quantitative measurement of vibration perception thresholds in patients treated with cisplatin is a relatively simple, accurate and reliable technique. Measurement is only required at the hand. It is concluded that this technique is a valuable tool in the assessment of cisplatin neurotoxicity and may be used in the monitoring of drugs that claim to be of benefit in the prevention and treatment of this affliction. PMID- 2592982 TI - Effects of traverse length on human perioral directional sensitivity. AB - The capacity of 8 neurologically healthy adults to distinguish direction of motion on the skin overlying the mental foramen was determined. The velocity, orientation, and the length and width of skin traversed by the moving tactile stimuli were precisely controlled. Directional sensitivity, d', was found to depend on both stimulus velocity and the length of skin traversed. Since the relationship between d' and velocity at each traverse length was well described by a generalized gamma function, it was possible to quantitatively characterize the effects of changes in traverse length on the relationship between d' and velocity. Specifically, peak (i.e., maximal) directional sensitivity increased as the length of skin traversed was increased, yet the velocity which resulted in peak directional sensitivity (i.e., the optimal or model velocity) remained invariant over the range of traverse lengths investigated (0.35-1.0 cm). The effect of stimulus velocity on directional sensitivity was least at the longest traverse lengths used. The generalized gamma function model fit the relationship between directional sensitivity and velocity equally well at all traverse lengths studied. The results lead us to anticipate that stimuli of the type used in this study should prove valuable for the detection and quantification of disturbances in orofacial tactile spatiotemporal integration in patients with peripheral nerve injury. PMID- 2592983 TI - Modulation of flexor carpi radialis H reflex by lateral tilts in man. AB - Static vestibular influences on upper limb flexor tone were studied in man by analyzing the changes in flexor carpi radialis H reflex area with lateral tilting of the longitudinal body axis. Ten healthy volunteers and 2 labyrinthine defective patients were tested in an experimental situation designed to minimize all afferent inputs except vestibular ones. Each subject was seated on a chair which could be tilted laterally to the left or the right from the vertical. Head and trunk were fixed upright, upper and lower limbs in half-flexed position and forearm in an intermediate position between supination and pronation. Lateral tilting was applied at random from the vertical (0 degrees control position) to left and right (4 degrees, 8 degrees, 12 degrees, 16 degrees, 20 degrees test positions). Each test position was followed by a return to 0 degrees and in each control and test position 20 consecutive H reflexes were recorded. The data observed in the normal subjects showed flexor tone inhibition in the arm which was tilted downwards and facilitation in the contralateral arm. These findings suggest that in man, like in animals, labyrinth reflexes act asymmetrically and in the opposite direction to neck reflexes. PMID- 2592984 TI - Immunochemical analysis of alpha-actinin of nemaline myopathy after two dimensional electrophoresis. AB - We analyzed alpha-actinin from human skeletal muscle by immunoblotting after two dimensional electrophoresis. A monoclonal antibody, S alpha 5-17, was established after immunization in Balb/c mouse with crude alpha-actinin fraction from human soleus muscle. Western blotting and indirect immunofluorescence microscopy revealed that the antibody reacted selectively with alpha-actinin from human skeletal muscle and stained in a manner equivalent to that of type 1, 2A, 2B and 2C myofibers and cardiac atrial and ventricular muscles. No reactivity was observed in the arterial smooth muscle layer or in the central and peripheral nervous systems. The antibody exhibited 2 spots with different isoelectric points in a range more basic than that of actin upon immunoblotting after two dimensional gel electrophoresis, suggesting the presence of 2 variants of alpha actinin in human skeletal muscle. Analysis of type 2B-deficient muscle with nemaline myopathy or central core disease revealed that type 2B myofibers contained the basic variant, while type 1 and 2A myofibers contained only the acidic variant. Immunoblots performed after two-dimensional gel electrophoresis of muscles with nemaline myopathy revealed alpha-actinin variants indistinguishable from those of control muscles. PMID- 2592985 TI - Herpes simplex virus type 2 transcripts in trigeminal ganglia during acute and latent infection in mice. AB - Adult mice were inoculated intracerebrally with herpes simplex virus type 2 (HSV 2), and perfused at days 5, 8, 81, 108, and 130 after infection. Trigeminal ganglia and roots were dissected out and embedded in paraffin. Four 35S-labelled DNA probes that contained immediate-early (ICP-0, ICP-4), delayed-early (thymidine kinase; TK), or late (morphological transforming region; MTR) genes were prepared. In situ hybridization methods or an immunoperoxidase antigen method using HSV-2 antibody were applied to serial sections. During acute infection, use of each of the 4 probes (ICP-0, ICP-4, TK, MTR) gave hybridization signals in a distribution similar to that of antigen. During latent infection, only the ICP-0 probe gave hybridization signals overlying neurons, while in adjacent sections, the other probes (ICP-4, TK, MTR) did not show signals. No antigen was detected during latency. Hybridization signals were also demonstrated in nuclei of neurons during latency using a non-radioactive ICP-0 probe labelled with a steroid hapten. These results suggest that the transcription of the HSV-2 genome is restricted during latency, with transcript localization to nuclei of neurons as has been described in latent HSV-1 infection. Evidence for latent ganglionic infection by in situ hybridization in this model is consistent with that obtained by ganglionic explanation and by reactivations induced by immunosuppression. PMID- 2592986 TI - Lysophosphatidylcholine-induced incipient demyelination: involvement of a new tubular structure. AB - Demyelination was induced in the rat sciatic and tibial nerves by microinjection with lysophosphatidylcholine (LPC). Accompanying early myelin lysis (1-24 h) was the formation of vesicles and tubular structures. The tubules which are novel structures have a diameter range of 24-27 nm, a centre-to-centre spacing 30-50 nm and may extend for 3 microns in length. In this form they are arranged as a monolayer in the periaxonal space. As demyelination progressed and the periaxonal space widened the tubules increased in number and became more irregularly arranged. The tubules are apparently derived from the myelin lamellae/Schwann cell plasma membrane, while the axolemma remains intact. PMID- 2592987 TI - Anti-neuroblastoma antibodies in myasthenia gravis: clinical and immunological correlations. AB - Forty-four of 109 myasthenia gravis (MG) patients (40%) had serum antibodies against human neuroblastoma cells (NBL). Anti-NBL antibodies were most frequent in the sera of MG patients who had either a hyperplastic thymus or a thymoma, clinically mild to moderately severe generalized MG, and a long disease duration (greater than or equal to 11 years). No correlation between individual anti-NBL antibody and anti-acetylcholine receptor (AChR) antibody titers was observed. Seven of the 19 patients negative for anti-AChR antibodies (37%) had anti-NBL antibodies in their sera. These findings provide further evidence for immunological heterogeneity in MG. In addition to the typical autoantibodies to the AChR, autoimmunization against neural antigens can frequently be detected in these patients. PMID- 2592988 TI - Familial intermittent ataxia due to a defect of the E1 component of pyruvate dehydrogenase complex. AB - Disturbances of pyruvate metabolism have been implicated in the aetiology of several neurological disorders including Leigh's disease and familial ataxia. We have re-investigated a patient whose initial description documented intermittent ataxia, a presumed disorder of pyruvate metabolism and an X-linked pattern of inheritance. Recent studies showed he had slow oxidation of pyruvate, low pyruvate dehydrogenase complex (PDC) activity and immunochemical evidence of E1 deficiency in skeletal muscle mitochondria. This is consistent with the recent finding that the gene for E1 alpha is on the X chromosome. PMID- 2592989 TI - Are there antilymphocyte autoantibodies in multiple sclerosis patients? AB - Immunoglobulins were separated from sera of 40 multiple sclerosis (MS) patients and 40 healthy controls by density and affinity chromatography. In IgM and IgG fractions of the sera of patients and controls no lymphocyte-specific binding could be detected with the help of FITC-conjugated anti-mu and anti-Fc antibodies. PMID- 2592990 TI - Late onset cerebello-pontomesencephalic degeneration. AB - Two siblings are presented with late onset, rapidly progressive truncal ataxia, paralysis of down-gaze and loss of up-gaze saccades in association with other oculomotor dysfunctions as well as dementia. Electron microscopic muscle studies revealed abnormal distribution and form of the mitochondria, probably being the ultrastructural basis of the pathologic changes. A neurological syndrome as that described here has not been reported before. PMID- 2592991 TI - Myofibrillar protein catabolism in rat steroid myopathy measured by 3 methylhistidine excretion in the urine. AB - The fractional rate of breakdown of myofibrillar protein in rat skeletal muscle was measured during subcutaneous cortisone acetate treatment (10 mg/100 g body weight per day). The daily urinary excretion of 3-methylhistidine divided by the 3-methylhistidine pool of the skeletal muscle was used to determine the fractional breakdown rate of myofibrillar protein. The mean fractional breakdown rate remained within the normal range throughout the first 5 days, but decreased significantly from the 16th day of treatment. When the daily 3-methylhistidine excretion was divided by the creatinine excretion, the rate showed the same trend of change. These results strongly suggest that the loss of myofibrillar protein induced by cortisone administration is not caused by increased breakdown but by decreased synthesis. PMID- 2592992 TI - Tissue banking and EURAGE. PMID- 2592993 TI - The firing of hippocampal place cells predicts the future position of freely moving rats. AB - Direct observation and automatic, video-based methods reveal that a large fraction of hippocampal pyramidal neurons recorded from freely moving rats behave as "place cells"; the firing of each place cell occurs almost exclusively when the rat is in a restricted part of its current environment. In earlier work, 2 dimensional firing distributions for place cells over the apparatus area were made under the assumption that the correct location for each spike was the animal's position at the instant that the spike was fired. Spatial firing distributions generated in this way often have a very simple structure, in which the single region of intense activity has a just one maximum, and where the rate decreases monotonically in all directions away from the maximum. We will refer to patterns of this sort as "ideal." We describe how the spatial firing pattern is altered by assigning spikes to positions earlier or later than the instant at which they were fired. Spatial firing distributions were generated for a range of constant displacements of the spike time-series against the position time series. Three quantitative measures were used to estimate the extent to which the spatial firing pattern at different "spike/position shifts" approximated the ideal pattern. The 3 measures are in agreement that spikes must precede the animal's position by about 120 msec for the spatial firing pattern to be closest to the ideal. These results suggest that hippocampal unit activity predicts the animal's future location on a short time scale. PMID- 2592995 TI - Age of differentiation determines rat retinal germinal cell phenotype: induction of differentiation by dissociation. AB - We are interested in the mechanisms that control cell phenotype during the development of the CNS. Since different neuronal types arise at different times during neurogenesis in the retina, we predicted that the factors that determine cell type must be developmentally regulated as well. To test this hypothesis, we induced retinal germinal cells to differentiate at different ages by dissociating the retina into single cells and culturing them on a variety of substrates. Prior to dissociation, the S-phase germinal cells were labeled with 3H-thymidine so that their fate could be specifically followed. We found that our culture conditions promoted the differentiation of the majority of the germinal cells and that these cells differentiated into different neuronal types depending on the age of the animal from which the retina had been taken; embryonic day 14 germinal cells differentiated primarily into ganglion cells, and never produced rods, while germinal cells from postnatal day 1 retina differentiated into rods, but not ganglion cells. These results are consistent with the hypothesis that temporally regulated factors determine cell phenotype during the development of the retina. PMID- 2592994 TI - Ultrastructural localization of molecular subtypes of immunoreactive neural cell adhesion molecule (NCAM) in the adult rodent striatum. AB - Neural cell adhesion molecule (NCAM) is a plasma membrane glycoprotein that is thought to mediate adhesion between neuronal elements and play an important role in neural development. Although NCAM has been found in the adult brain, as well as the developing brain, little is known about its function or ultrastructural distribution. A monoclonal antibody which was directed against embryonic (E15 E17) mouse brain and identified 180 and 140 kDa molecular weight forms of NCAM was used to examine the immunohistochemical localization of NCAM in the rodent striatum. Light microscopic results in the adult mouse and rat showed that most NCAM180,140 immunoreactivity was localized to the relatively small population of medium and large-sized aspiny interneurons of the caudate nucleus and to the majority of neurons in the globus pallidus. Ultrastructural analysis revealed that reaction product in aspiny somata was present in discrete, closely spaced patches of cytoplasm along the inner face of the plasma membrane and was also prominent in somatic protrusions which were frequently apposed to synapsing axons. Distal aspiny and pallidal dendrites containing NCAM180,140 received numerous synaptic inputs. Within caudate neuropil NCAM180,140 was also present in spines with thin necks and small spine heads which were postsynaptic to unlabeled axon terminals and in preterminal (unmyelinated) axons and terminal boutons that issued from myelinated bundles and formed asymmetric synapses with unlabeled dendritic spines. This study provides the first evidence in adult brain that NCAM180,140 varies in extent and location within neurons. The heterogeneous distribution of NCAM180,140 in neurons of the basal ganglia may be related to a number of functions such as maintaining or modulating the density and distribution of synaptic inputs and the formation of new contacts on dendritic spines. PMID- 2592996 TI - Distribution of calcium currents in sprouting PC12 cells. AB - Whole-cell calcium and barium currents were recorded from PC12 cell bodies and growth cones during nerve growth factor (NGF)-induced neurite outgrowth. Depolarizing voltage steps were applied to activate the currents, and pharmacological agents were used to separate them from other ionic currents. In recordings from growth cones still attached to neurites, current flow from central parts of the cell could be distinguished from the growth cone currents. On the other hand, currents from neuritic shafts and growth cones contributed to whole-cell currents recorded in the soma. Such currents were isolated by alternatively comparing recordings of whole-cell calcium currents with recordings in which calcium currents of defined parts of the cell were suppressed by exposing these regions to laminar streams of solutions with low calcium. The boundary between such streams and the bath solution was shown to be sharp using a calcium-selective microelectrode. The current deficits recorded when the growth cones were exposed to solutions with low calcium (growth cone currents) were within 10-50% of the total cell currents and similar to the currents recorded when the whole cell except the growth cone was exposed to low calcium. The current densities in the growth cones during initial sprouting were 5.4 times higher than those in the somata. Growth cone currents showed more inactivation than currents originating from the soma during pulses of 200 msec. In most experiments no calcium currents could be resolved in the neuritic shaft during initial neurite growth (1-10 d of NGF application), indicating low current density. In proximal segments of the neurites, however, a somatofugal decrease of the current density was observed. It is concluded from these results, that in outgrowing neurites of PC12 cells high densities of calcium channels are maintained in the growth cones, whereas in the neuritic shaft calcium channel density is initially low and later increases during consolidation of the neurites. PMID- 2592997 TI - Depletion of serotonin in the nervous system of Aplysia reduces the behavioral enhancement of gill withdrawal as well as the heterosynaptic facilitation produced by tail shock. AB - Noxious stimuli, such as electrical shocks to the animal's tail, enhance Aplysia's gill- and siphon-withdrawal reflex. Previous experimental work has indicated that this behavioral enhancement, known as dishabituation (if the reflex has been habituated) or sensitization (if it has not been habituated), might be mediated, at least in part, by the endogenous monoaminergic transmitter serotonin (5-HT). To assess 5-HT's role in dishabituation and sensitization of Aplysia withdrawal reflex, we treated Aplysia with the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). We found that 5,7-DHT treatment significantly reduced the dishabituation of the withdrawal reflex produced by tail shock. Treatment with the neurotoxin also blocked the heterosynaptic facilitation of monosynaptic connections between siphon sensory neurons and their follower cells, which contributes to the behavioral enhancement. Analysis by high-performance liquid chromatography indicated that 5,7-DHT treatment significantly reduced 5-HT levels in the Aplysia CNS. Moreover, the neurotoxic effects of 5,7-DHT appeared to be relatively specific for serotonergic pathways. Thus, 5,7-DHT treatment did not disrupt the ability of nonserotonergic facilitatory interneurons, the L29 cells, to facilitate the connections of siphon sensory neurons. Also, 5,7-DHT reduced 5-HT-dependent, but not dopamine-dependent, histofluorescence in Aplysia central ganglia. Finally, 5,7-DHT does not reduce the levels of the facilitatory peptides SCPA and SCPB within the Aplysia CNS. Our results, together with those of Mackey et al. (1989), indicate that 5-HT plays a major role in mediating dishabituation and sensitization of Aplysia's withdrawal reflex. PMID- 2592998 TI - Localization of potential serotonergic facilitator neurons in Aplysia by glyoxylic acid histofluorescence combined with retrograde fluorescent labeling. AB - A variety of evidence suggests that 5-HT participates in presynaptic facilitation of the siphon sensory cells contributing to dishabituation and sensitization of the gill- and siphon-withdrawal reflex in Aplysia. Most recently, Glanzman et al. (1989) have shown that the 5-HT neurotoxin 5,7-DHT markedly reduces both the synaptic facilitation and behavioral dishabituation produced by tail shock. To provide more direct evidence for a role of 5-HT, I have used histological techniques to try to locate individual serotonergic facilitator neurons. I first used a modification of the glyoxylic acid histofluorescence technique to map serotonergic and dopaminergic neurons in the CNS of Aplysia. Intracellular fluorescent labeling combined with histofluorescence indicates that the previously identified L29 facilitator neurons are not serotonergic. Nerve transection experiments suggest that most of the perisomatic 5-HT histofluorescence in the abdominal ganglion (the location of the siphon sensory cells) comes from neurons whose cell bodies are located in the pedal or cerebral ganglia. As there are at least 500 serotonergic neurons in those ganglia, I combined retrograde fluorescent labeling with histofluorescence to identify a small subset of those neurons which send processes to the abdominal ganglion and are therefore potential serotonergic facilitators. In the following paper, Mackey et al. (1989) show that stimulation of 2 of those neurons in the cerebral ganglia (the CB1 cells) produces presynaptic facilitation of the siphon sensory cells contributing to dishabituation and sensitization of the withdrawal reflex. PMID- 2592999 TI - Identified serotonergic neurons LCB1 and RCB1 in the cerebral ganglia of Aplysia produce presynaptic facilitation of siphon sensory neurons. AB - Several lines of evidence suggest that 5-HT plays a significant role in presynaptic facilitation of the siphon sensory cells contributing to dishabituation and sensitization of the gill- and siphon-withdrawal reflex in Aplysia. Most recently, Glanzman et al. (1989) found that treatment with the 5-HT neurotoxin, 5,7-DHT markedly reduced both synaptic facilitation and behavioral dishabituation. To provide more direct evidence for a role of 5-HT, we have attempted to identify individual serotonergic facilitator neurons. Hawkins (1989) used histological techniques to locate several serotonergic neurons in the ring ganglia that send axons to the abdominal ganglion and are therefore possible serotonergic facilitators. These include one neuron in the B cluster of each cerebral ganglion, which we have identified electrophysiologically and named the CB1 cells. Both glyoxylic acid histofluorescence and 5-HT immunofluorescence indicate that the CB1 neurons are serotonergic. In a semiintact preparation, the CB1 neurons respond to cutaneous stimulation which produces dishabituation and sensitization (such as tail shock) with an increase in firing, which may outlast the stimulation by 15 min. Intracellular stimulation of a CB1 neuron in a manner similar to its response to tail shock produces facilitation of the EPSPs from siphon sensory neurons to motor neurons, as well as broadening of the action potential in the sensory neurons in tetraethylammonium solution. These results strongly suggest that the identified serotonergic CB1 neurons participate in mediating presynaptic facilitation contributing to dishabituation and sensitization of the gill- and siphon-withdrawal reflex in Aplysia. PMID- 2593000 TI - Identified facilitator neurons L29 and L28 are excited by cutaneous stimuli used in dishabituation, sensitization, and classical conditioning of Aplysia. AB - Tactile or electrical stimulation of the skin can be used to produce dishabituation, sensitization, and classical conditioning of the gill- and siphon withdrawal reflex in Aplysia. These behavioral effects are thought to involve presynaptic facilitation at the synapses from siphon sensory neurons to gill and siphon motor neurons. Facilitation of PSPs onto the motor neurons can also be produced by intracellular stimulation of single identified neurons in the abdominal ganglion, including L29 and L28. In this paper, we further characterize L29 and L28. First, we show that they are excited by cutaneous stimuli similar to those used to produce dishabituation, sensitization, and classical conditioning and may therefore participate in mediating those behavioral effects. The results are also consistent with a possible role of L29 and L28 in higher-order features of conditioning. Second, we show that 5-HT does not mimic some of the PSPs of L29, in agreement with previous evidence that L29 is not serotonergic. Third, we present 2 types of evidence that L29 acts directly to produce facilitation of the sensory cells: (1) L29 comes into close contact with sensory cells in fluorescent double-labeling experiments, and (2) L29 produces facilitation of sensory cells in dissociated cell culture. Together with the results of the preceding paper (Mackey et al., 1989), these results indicate that facilitation of sensory cell synapses contributing to behavioral enhancement of the reflex can be produced by identified neurons that use 2 different transmitters: 5-HT (the transmitter of CB1) and the unknown transmitter of L29. PMID- 2593001 TI - Task-dependent field potentials in human hippocampal formation. AB - Task-dependent field potentials were recorded from implanted electrodes located in the hippocampus and other medial temporal lobe (MTL) structures of epileptic patients undergoing evaluation for possible surgery. In 2-alternative categorization tasks, low-probability auditory, somatic, and visual stimuli elicited potentials with large amplitudes and sharp spatial gradients having the following characteristic spatial distribution: positive posterior to the hippocampus, negative within the hippocampus, and positive anterior to the hippocampus. The sharp spatial gradients within the MTL suggest that these potentials were locally generated, probably by hippocampal pyramidal cells. The MTL potentials were also reliably elicited by exemplars of semantic categories and by stimulus omissions and were sensitive to the sequence of preceding stimuli. However, they were not elicited by the same stimulus sequences when the patient's attention was directed elsewhere and categorization was not required. These results indicate that the MTL potentials reflect endogenous as opposed to obligatory processes. The time course and task dependence of the MTL potentials suggest that MTL structures could contribute to P300 and related event-related potentials on the scalp. PMID- 2593002 TI - Organized arrangement of orientation-sensitive relay cells in the cat's dorsal lateral geniculate nucleus. AB - We studied the physiological orientation biases of over 700 relay cells in the cat's dorsal lateral geniculate nucleus (LGNd). Relay cells were sampled at regular intervals along horizontally as well as vertically oriented electrode penetrations in a fashion analogous to that used previously in studies of visual cortex (Hubel and Wiesel, 1962). The strengths of the orientation biases and the distributions of the preferred orientations were determined for different classes of relay cells, relay cells in different layers of the LGNd, and relay cells subserving different parts of the visual field. We find that, at the population level, LGNd cells exhibit about the same degree of orientation bias as do the retinal ganglion cells providing their inputs (see also Soodak et al., 1987). Also, as in the retina (Levick and Thibos, 1982; Leventhal and Schall, 1983), most LGNd cells tend to prefer stimuli oriented radially, i.e., parallel to the line connecting their receptive fields to the area centralis projection. However, the radial bias in the LGNd is weaker than in the retina. Moreover, there is a relative overrepresentation of cells preferring tangentially oriented stimuli in the LGNd but not in the retina. As a result of the overrepresentation of cells preferring radial and tangential stimuli, the overall distribution of preferred orientations varies in regions of the LGNd subserving different parts of the visual field. Reconstructions of our electrode penetrations provide evidence that, unlike in the retina, cells having similar preferred orientations are clustered in the LGNd. This clustering is apparent for all cell types and in all parts of laminae A and A1. The tendency to cluster according to preferred orientation is evident for cells preferring radially, intermediately, and tangentially oriented stimuli and thus is not simply a reflection of the radial bias evident among retinal ganglion cells at the population level. It is already known that cells having inputs from different eyes, on-center, off-center, X-, Y , W-type, and color-sensitive ganglion cells are distributed nonrandomly in the LGNd of cats and monkeys (for review, see Rodieck, 1979; Stone et al., 1979; Lennie, 1981; Stone, 1983). The finding that relay cells having similar preferred orientations are also distributed nonrandomly suggests that the initial sorting of virtually all properties segregated in visual cortex may begin in the LGNd. PMID- 2593003 TI - Identification of proteins that are developmentally regulated during early cerebral corticogenesis in the rat. AB - Between embryonic day 14 (E14) and embryonic day 21 (E21), the rat neopallium develops from a relatively homogeneous band of mitotic precursor cells into a complex laminated structure containing diverse classes of neurons. In order to identify some of the molecular components underlying this process, 2-dimensional PAGE was used to compare proteins expressed before cortical neurons are born (E14) with those expressed during neurogenesis and neuronal migration (E17 and E21). This approach has permitted the identification of 15 proteins that show greater than 3-fold changes in their rate of accumulation between E14 and E21. Six proteins show consistent up-regulation, ranging from 3.2- to 10.7-fold. Five proteins show consistent down-regulation ranging from 9- to 22-fold. Four proteins that appear at E21 are not detectable on fluorograms of E14 cortex, even after long exposures, and thus are up-regulated more than 200-fold from E14 to E21 and may be considered to appear de novo. The molecular weights and isoelectric points of most of these 15 suggest that they are previously unreported, developmentally regulated proteins. Comparisons of gels of cortex to gels of lung and heart suggest that several of these proteins are enriched in brain relative to non-neural tissues. This analysis also indicates that, despite the large morphogenic changes observed during this developmental period, few proteins (less than 3%) among the total spectrum analyzed show large changes in their rates of synthesis. PMID- 2593004 TI - Lesions of perirhinal and parahippocampal cortex that spare the amygdala and hippocampal formation produce severe memory impairment. AB - In monkeys, bilateral damage to the medial temporal region produces severe memory impairment. This lesion, which includes the hippocampal formation, amygdala, and adjacent cortex, including the parahippocampal gyrus (the H+A+ lesion), appears to constitute an animal model of human medial temporal lobe amnesia. Reexamination of histological material from previously studied monkeys with H+A+ lesions indicated that the perirhinal cortex had also sustained significant damage. Furthermore, recent neuroanatomical studies show that the perirhinal cortex and the closely associated parahippocampal cortex provide the major source of cortical input to the hippocampal formation. Based on these 2 findings, we evaluated the severity of memory impairment in a group of monkeys that received bilateral lesions limited to the perirhinal cortex and parahippocampal gyrus (the PRPH lesion). The performance of the PRPH group was compared with that of monkeys with H+A+ lesions, who had been studied previously, and with a group of normal monkeys. Monkeys with PRPH lesions were severely impaired on 3 amnesia-sensitive tasks: delayed nonmatching to sample, object retention, and 8-pair concurrent discrimination. On pattern discrimination, a task analogous to ones that amnesic patients perform well, monkeys in the PRPH group performed normally. Overall, monkeys with PRPH lesions were as impaired or more impaired than the comparison group of monkeys with H+A+ lesions. These and other recent findings (Zola-Morgan et al., 1989b) suggest that the severe memory impairment in monkeys and humans associated with bilateral medial temporal lesions results from damage to the hippocampal formation and adjacent, anatomically related cortex, not from conjoint hippocampus-amygdala damage. PMID- 2593005 TI - Multiple electrosensory maps in the medulla of weakly electric gymnotiform fish. I. Physiological differences. AB - The electrosensory lateral line lobe in the weakly electric gymnotiform fish Eigenmannia contains 3 topographic maps of high-frequency (tuberous) electroreceptive information from the body surface. The maps receive identical primary afferent input since axonal collaterals of both amplitude- and phase coding afferents project to all 3 maps (Heiligenberg and Dye, 1982). Response properties of the amplitude-coding pyramidal neurons in the multiple maps were investigated in order to determine whether the maps differ physiologically. Units in the lateral map have larger receptive fields and are more sensitive than units in the centromedial map. The former units respond more phasically and with shorter latencies to step changes in stimulus amplitude (measured from the stimulus onset to the maximum response). Although 75% of pyramidal cells in all maps show a center-surround receptive-field organization, the strength of the inhibitory surround varies among maps, tending to be weakest for units in the lateral map and strongest for units in the centromedial map. Pyramidal neurons also differ in their responses with respect to the temporal frequency of amplitude modulations; the majority of units in the lateral map prefer high temporal frequencies, while those in the centromedial map prefer low frequencies. These results suggest that the multiple electrosensory maps could provide the initial separation of spatial and temporal processing of sensory information, much as has been suggested for X and Y ganglion cells in the cat retina (Shapley and Perry, 1986). The centromedial map could provide high spatial contrast with correspondingly poor temporal resolution, while the more sensitive units in the lateral map could best provide information about temporal changes in stimulus amplitude. PMID- 2593006 TI - Effects of dopamine depletion on striatal neurotensin: biochemical and immunohistochemical studies. AB - Interactions between striatal dopamine (DA) and neurotensin (NT) have been suggested by anatomical, behavioral, and biochemical studies. Nigrostriatal DA neurons, in contrast to mesocorticolimbic DA neurons, do not appear to contain NT. Thus, distinct neuronal elements subserve interactions between DA and NT within the striatum. We have previously demonstrated that reserpine-induced depletion of striatal DA is accompanied by a dose- and time-dependent increase in striatal NT concentrations. In order to further characterize the effects of reserpine and to define the mechanism by which reserpine acts to increase striatal NT concentrations, we have used immunohistochemical and biochemical approaches. Immunohistochemical examination of rats pretreated with reserpine revealed marked increases in the density of NT-like immunoreactive (NT-li) perikarya and fibers, and the development of NT-li patches. Pretreatment with reserpine had no apparent effect on NT synthesis, as assessed by examination of cycloheximide-induced inhibition of protein synthesis. However, reserpine administration resulted in a significant decrease in the release of both DA and NT into the striatal extracellular fluid, as measured by in vivo microdialysis. These data suggest that the increase in striatal NT concentrations observed after reserpine treatment results from decreased release, rather than increased synthesis of the peptide. PMID- 2593007 TI - Histochemical visualization of neutral endopeptidase-24.11 (enkephalinase) activity in rat brain: cellular localization and codistribution with enkephalins in the globus pallidus. AB - We have developed a novel fluorescent histochemical method to localize the enzyme neutral endopeptidase-24.11 (NEP, E.C. 3.4.24.11, enkephalinase) in the rat brain in order to directly compare the relative distributions of the enzyme and its putative peptide substrate, the enkephalins. The method is based on the sequential cleavage of the synthetic peptide substrate, glutaryl-alanyl-alanyl phenylanyl-4-methoxy-2-naphthylamide, by NEP and exogenous aminopeptidase M to yield free 4-methoxy-2-naphthylamine (MNA). In the presence of nitrosalicylaldehyde, free MNA is captured, yielding an insoluble yellow fluorescent precipitate which marks the site of NEP activity. The specificity of the method was demonstrated using the selective NEP inhibitors thiorphan, phosphoramidon, and JHF26. All NEP staining throughout the brain was abolished using a 50-nM concentration of these inhibitors. The enzyme was richly localized to many regions, including the cerebral cortex, caudate putamen, globus pallidus, hippocampus, substantia nigra, periaqueductal gray, several cranial nerve nuclei, nuclei of the reticular formation of the medulla. In most regions, reaction product was associated with cell bodies of varying size and morphology. In a number of regions, colchicine increased the amount of NEP staining, particularly in cell processes. The regional distribution pattern of the enzyme, however, did not change in response to colchicine and was similar to that of untreated animals. The histochemical localization of NEP was combined with fluorescent immunocytochemical visualization of the enkephalins in order to localize both in the same tissue section. In the globus pallidus, this combined fluorescent technique revealed numerous NEP-positive cell bodies surrounded by fiber pathways displaying intense enkephalin-like immunoreactivity. The source of the NEP in the globus pallidus was studied using the neurotoxic agent, N-methyl-D-aspartate (NMDA). A pronounced decrease in NEP cellular staining was observed within 7 d in response to NMDA, persisted for at least 16 weeks, and correlated with injury of pallidal neurons. There was no apparent change in enkephalin-like immunoreactivity in the globus pallidus in response to NMDA. These data provide evidence that NEP and enkephalin in the globus pallidus derive from different sources. This study supports the hypothesis that NEP localizes to enkephalin-rich regions of the rat brain, and that the enzyme may be involved in the inactivation of synaptically released enkephalins. PMID- 2593008 TI - Evaluation of human serum based tumor marker control. AB - A human serum based tumor marker control containing 13 antigen associated with tumors or cancer cell proliferation has been developed for use in quality control of various cancer diagnostic test methodologies. The menu is comprehensive including several new antigens: the Carbohydrate Antigens 125 and 19-9, Tissue Polypeptide Antigen (TPA), Beta-2-microglobulin, as well as some traditional markers; CEA, AFP and PAP. The control is bilevel; Level I representing low values and Level II showing elevated or clinically significant values, designed to control the linear range of the assays. Stability of reconstituted material is 14 days at 2-8 degrees C and 30 days at -20 degrees C. Accelerated stress testing shows that the lyophilized material is stable for 3 years when stored at 2-8 degrees C. Testing was completed using commercially available RIA and IRMA assays. The product contains no azide or other preservatives that may interfere in these immunoassays. This product is designed for use in cancer antigen testing as part of a quality assurance program. This control will effectively assist in evaluating the accuracy and precision of immunoassay methods used in cancer evaluation. PMID- 2593009 TI - Exact timing of the one-hour glucose sample as a factor in the screen for gestational diabetes. AB - We examined the exactness of the timing of the 1-hour glucose sample following a 50-g oral glucose challenge as a critical variable in interpretation of the test. Heparin locks were placed in 45 pregnant patients between 25 and 28 weeks' gestation, and 5 patients between 30 and 33 weeks' gestation. Venous samples were taken at intervals of 50, 60, and 70 minutes from completion of the ingestion of a 50-g oral glucose load. We found all of the nine possible patterns of blood glucose values that can derive from three sequential values. There was no consistent relationship between these 60 +/- 10 minute values. Two of the patients had a 60-minute value greater than 140 mg/dL, but a 50- or 70-minute value that was less than 140 mg/dL. Four of the patients had a 50- or 70-minute value that was greater than 140 mg/dL, but a 60-minute value that was less than 140 mg/mL. The range of results in this study reflects a continuum of values that change rapidly over time and in patterns that are not predictable. We conclude that accurate timing is important to avoid erroneous interpretation of the 1-hour glucose screen. PMID- 2593010 TI - Umbilical artery catheter position and intraventricular hemorrhage. AB - A historical cohort study was designed to examine high (T6-T11) versus low (L3 L5) umbilical artery catheter (UAC) positioning as a risk factor for subependymal/intraventricular hemorrhage (SEH/IVH) in very low birthweight infants. High and low UAC groups were similar for mode of delivery, severity of pulmonary disease, weight, gestation, Apgar scores, and air leak. Seventeen of 36 infants with high UACs and 6 of 44 infants with low UACs developed SEH/IVH. The incidence (P less than .001) and severity (P less than .01) of SEH/IVH was significantly greater in the high UAC positioning group. Retrograde arterial flow with or without embolization to the cerebral circulation from high UAC positioning is suggested as a possible cause for the association between high UAC positioning and SEH/IVH. PMID- 2593011 TI - Dynamic skinfold measurements to assess fluid status in low birthweight infants. Part 1: Data acquisition and processing. AB - To evaluate the measurement of fluid status in the premature neonate using dynamic skinfold thickness (DST) measurement, a pair of calipers were interfaced to a computer, and weight and digital DST at four sites were measured daily in 24 neonates in the postnatal weight loss period. A biexponential equation was fitted to each curve from the instant the rate of caliper closure fell below 2 mm/s, and the five constants obtained used in a search for a parameter that correlated with the percentage of weight loss. The percentage of fall in the DST from 0.4 to 30 seconds yielded highest mean of individual coefficients of determination (COD) (0.83); the percentage of fall from 0.7 to 35 seconds yielded highest COD in pooled data (0.56). Expected weight loss can be predicted with standard error of 2.9% with pooled regression but with standard error of 1.3% using individual correlations. We conclude that individuals lose fluid in a consistent manner during this period but that interindividual differences are large and require further investigation. PMID- 2593012 TI - Dynamic skinfold measurements to assess fluid status in low birthweight infants. Part 2: Correlation with postnatal weight changes. AB - Computerized recording of dynamic skinfold thickness measurements was performed on low birthweight infants. Four skinfold sites were measured daily for the first 7 days postnatally and then at intervals up to 4 weeks of age. The percentage of fall of the skinfold between 0.4 and 30 seconds after caliper application was shown to correlate best with postnatal weight loss until minimum weight was reached. Of the 24 infants studied in detail, only two had a correlation coefficient less than 0.75 between changes in the percentage of fall of the skinfold and postnatal weight changes. There was, however, marked individual variation in the amount of weight loss for a given reduction in the percent of the skinfold. Assuming that most of the postnatal weight loss of low birthweight infants is due to reduction of extracellular volume, dynamic skinfold thickness appears to be a good noninvasive measure thereof. PMID- 2593013 TI - The impact of gestational age on dysmaturity/postmaturity. AB - The medical records of 403 infants admitted to the neonatal intensive care unit were reviewed. All were postterm (greater than or equal to 42 weeks' gestation) infants or infants who were full term (greater than or equal to 38 weeks' gestation) and had clinical diagnoses associated with the neonatal postmaturity/dysmaturity syndrome. Data collected from these 403 records were used to generate frequency distribution tables for a variety of obstetric and neonatal outcome variables. Regression analyses were used to assess associations among these variables and the presence or absence of fetal malnutrition (dysmaturity) or postdatism. Fetal distress and neonatal acidosis were associated with both dysmaturity and postdatism. Primigravidas, meconium-stained amniotic fluid, cesarean section, birth trauma, and neonatal death were associated with postdatism but not with dysmaturity. Preeclampsia, maternal smoking, oligohydramnios, low Apgar score, neonatal pulmonary hypertension, neurologic abnormalities, and a need for extracorporeal membrane oxygenation were associated with dysmaturity. No interaction between postdatism and dysmaturity was seen for any outcome variable. Postdatism and dysmaturity appear to contribute risk factors independently to infants admitted to the intensive care unit. PMID- 2593014 TI - Hypoglycemia due to high positioning of umbilical artery catheters. AB - Three neonates with umbilical artery catheters positioned at the eighth and tenth thoracic vertebrae experienced hypoglycemia that resolved rapidly upon withdrawal of the catheters to low positions between the third and fourth lumbar vertebrae. Streaming of glucose to the celiac and superior mesenteric arteries is a possible cause of this hypoglycemia. PMID- 2593015 TI - A model for diagnosis and initial therapy of pneumothorax in the neonate. AB - Treatment of pneumothorax may require prompt and aggressive medical management. Currently, the only models for practicing detection and evacuation of pneumothoraces are in living animals. This paper describes a simple doll model for diagnosis and treatment with needle aspiration. This easily made model demonstrates unilateral or bilateral pneumothorax to test the diagnostic and therapeutic capabilities of the trainee. The other major benefit is to avoid trauma or death in the living animal model. PMID- 2593016 TI - Neonatal skull depression: review of four cases. AB - Neonatal skull depressions may occur from traumatic delivery or abnormal intrauterine position. Surgery has been recommended when the condition is thought to threaten neurologic development; however, normal neurologic outcomes have been observed in conservatively managed infants. A review of four patients with neonatal skull depression is presented together with the obstetric history and findings from nursery examinations, skull roentgenograms, electroencephalograms, and follow-up pediatric visits. Two patients underwent surgical elevation of the depression, while two children with depressions of similar severity were managed without intervention. Neurologic and cosmetic outcomes have been normal in all four patients. It is suggested that uncomplicated depressions should be treated conservatively, with surgical elevation reserved for neonates with intracranial complications. PMID- 2593017 TI - A meconium suctioning device that is safe and practical. AB - Immediate suctioning of meconium from the trachea of newborns is believed to be an effective method for preventing or minimizing the meconium aspiration syndrome. Recently, however, the possibility of transmitting disease from the newborn to the physician or vice versa, while using the standard technique of direct oral suction (through a surgical mask), has been stressed. This has prompted the development of alternative methods for suctioning the newborn's trachea. These methods, while eliminating the possibility of disease transmission, create other problems. We, therefore, devised a technique for tracheal suctioning using inexpensive, readily available materials that is not only safe and effective in suctioning meconium but is also practical and easy to perform. PMID- 2593018 TI - Fathers grieve, too. PMID- 2593019 TI - The education of scientific physicians. PMID- 2593020 TI - Polemics in perinatology: the spies among us. PMID- 2593021 TI - Visual diagnosis casebook. Epignathus. PMID- 2593022 TI - Neonatal metabolic casebook. Hypernatremia and breast feeding. PMID- 2593023 TI - An unusual case presentation: pericardial tamponade complicating central venous catheter. AB - The use of central venous catheters in very low birthweight infants to provide adequate calories for growth is an integral part of the care of the high-risk neonate. The use of surgically placed Broviac catheters has been associated with infectious and mechanical complications. Recently, there has been increasing use of silastic central venous catheters inserted through a peripheral vein and advanced to the right atrium. These catheters have a reported low rate of complications. However, we report a case of a very low birthweight infant in whom a peripherally inserted silastic catheter perforated the wall of the right atrial appendage and led to fatal pericardial tamponade. This is a very rare but nearly always fatal complication. It is potentially avoidable by careful placement of the tip of the central venous catheter, so that it is not impinging on a wall of the heart. Serial venograms may be useful to reconfirm the position of the catheter. PMID- 2593024 TI - New technique for stabilizing umbilical artery catheters in very low birthweight infants. AB - The securing of umbilical artery catheters (UACs) with tape bridges has been associated with significant dermal complications in the very low birthweight neonate. We describe a new technique for UAC stabilization using an anchoring adhesive tape applied directly to the catheter, which is in turn sutured to the cord. This technique provides a very satisfactory method of UAC stabilization and avoids skin complications associated with the standard methods. PMID- 2593025 TI - A.B.C.'s periodontics. "G" is for gingival curettage. PMID- 2593026 TI - Is a prophylaxis really necessary prior to topical fluoride therapy? PMID- 2593027 TI - Dentin radiolucency in unerupted permanent mandibular molar: a case report. PMID- 2593028 TI - Oral Bacteroides. PMID- 2593029 TI - Clinical evaluation of individual films from double film packets. PMID- 2593030 TI - The complete exam and consultation format revisited. PMID- 2593032 TI - [90th meeting of the Otorhinolaryngological Society of Japan. 11-13 May, 1989, Osaka. Abstracts]. PMID- 2593033 TI - [Cochlear dysfunction induced by arterial obstruction in the cat anterior cerebellar artery]. AB - To determine the effects of circulatory disorder on the cochlear function, compound action potentials (AP) were measured in cats with the anterior cerebellar and the labyrinthine arteries occluded. While transitory AP depression followed the anterior cerebellar artery occlusion in approximately one third of the animals, there were no changes in the others. In contrast to this, AP disappeared rapidly in all cases with labyrinthine artery occlusion and recovered only after release of the occlusion in a period of time proportionate to the duration of occlusion. The different ways of response in the two occlusion sites seem to be attributed mainly to a greater chance of collateral circulations in the proximal. In addition, wide range of variance was observed from cat to cat in the effect of the anterior cerebellar artery occlusion and in the recovery following the release of occlusion in the labyrinthine artery, which may be attributed to anatomical variation inherent in the artery system. PMID- 2593031 TI - A.B.C.'s periodontics. "H" is for hormones. PMID- 2593034 TI - [Experimental study on the effect of the topical application of steroids on olfactory disturbance in mice]. AB - Although the topical treatment with steroids is the widespread method for olfactory disorders in human, the reports are limitted to clinical observations. The aim of this report is to evaluate the effect of topically applied of steroids in mice on the repairing course by the experimental olfactory disorders caused by zinc sulfate. The olfaction of mice was estimated by the record of behavioral task, using Cycloheximide, commonly used as repellent in rodents. When mice taste Cycloheximide for the first time, immediately the mice experience a very disagreeable taste leading to the simultaneous memory of the odor of Cycloheximide. Those who once experienced the taste and odor of Cycloheximide, will avoid simply by the odor next time. Two bottles were offered to mice, one containing distilled water and the other 0.01% Cycloheximide. When the mouse drank the distilled water, the response was interpreted as a correct response. When the Cycloheximide solution was chosen, an error. Twenty four mice were tested at ten times during a 10-minute trial, and the rates of correct response were counted. From the next day after the treatment of zinc sulfate, nasal application of 0.1% beta-methasone (group A), or nasal application of distilled water (group B) were applied to each group of twelve mice for five days. The results were as follows. 1. In the first experiment, the correct response was 85% (group A), and 80.8% (group B), however at the second trial, all responses were correct.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593036 TI - [Comparison of rhinomanometric values expressed by rate--validity and normal range]. AB - The nasal patency during respiration is today usually expressed by the nasal resistance. However, the nasal resistance is not the same throughout the total respiratory phase. Therefore, the reference point to express the resistance is therefore necessary to facilitate the mutual comparison of the data. The international committee for standardization of rhinomanometry has been paying a great effort to decide where this reference point should be set up, but has not yet reached the final consensus. The purpose of this study is to present a new method to estimate nasal respiratory conductivity, regardless of the reference point. Pressure flow curves during nasal respiration are quite similar in nature and rarely cross one another. The parabolic curves which do not cross each other can be superimposed by multiplying the standard equation, V = n.f(P). Accordingly, n is only one parameter in comparing these curves. A standard curve is decided as follows. Rohrer's equation was examined by polynomial regression analysis and concluded to be adequate to simulate a pressure flow curve. Rohrer's equation is converted to the function of P. Integration of this equation along P gives the value of the area under the curve (AUC). The total AUC can be obtained by simply adding the AUC of right and left sides. Definite integration from the origin to 1.0 and 2.0 on the abscissa gives the numerical value of AUC in each curve. The mean AUC is easily calculated by simple mathematical averaging of the data. K1 and K2 of the standard curve are calculated by solving simultaneous equations using mean AUC. K1 and K2 during expiration and inspiration are calculated, respectively. 718 subjects who had not been recently suffered from nasal diseases were examined by active anterior rhinomanometry. 47 functionally normal subjects in twenties were selected for calculation of the standard curve using the above mentioned method. In expiration, the values of K1 and K2 were 0.5476 and 1.3653, respectively. In inspiration, they were 0.4080 and 1.4750. Individual curve can be expressed by only one parameter. The normal range during nasal respiration is considered to be more than 0.7. The method presented in this study is convenient for the mutual comparison of the data both in clinical and basic research. PMID- 2593035 TI - [Nuclear DNA cytofluorometry of normal human laryngeal epithelia and squamous cell carcinoma]. AB - Normal human laryngeal epithelia and laryngeal squamous cell carcinoma were assayed by Feulgen DNA cytofluorometry using free cell nuclei isolated from carnoy-fixed, paraffin-embedded specimens. In all of the 12 normal specimens, the epithelium showed typical diploid cell clones with low proliferative activity. Polyploid cells were seen in only two specimens from subjects aged 61 and 69 years respectively, and the number of polyploid cells seen in these two specimens was only two. Fifteen cancer cases were divided into three groups: an untreated group (5 cases), a chemotherapy group (5 cases) and a group of cases with recurrence after radiation therapy (5 cases). Among these three groups the DNA ploidy patterns were compared. In the untreated group, all cases showed a two peak diploid pattern and a high proliferative activity, and polyploid cells were present. In the chemotherapy group, a wide one-peak histogram extending from 2C to about 5C was noted in 4 cases, and an aneuploid pattern in one case. Thus, the DNA ploidy pattern in the chemotherapy group differed from that in the untreated group. Of the 5 cases with recurrence after radiation therapy, one had a tetraploid pattern, but the remaining 4, a two-peak diploid pattern similar to that seen in the untreated group. Polyploid cells were observed in all these cancer cases. However, because they were also seen in some normal subjects, the finding of polyploid cells is not considered to be conclusive of cancer diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593037 TI - [Frequency specificity of ABR evaluated by tuning curves]. AB - A tone on tone simultaneous masking paradigm was used to determine tuning curves of ABR both from the normal and hearing-impaired subjects. ABR tuning curves were constructed to define masker intensity that resulted in a 50% reduction in probe elicited wave V amplitude. The frequency specificity of each probe stimulus was evaluated by Q10, low cut-off slope, high cut-off slope and the maximum masker frequency calculated for the tuning curves. The results were as follows; 1) Q10, low cut-off slope and high cut-off slope increased gradually with the increase in rise time. However, prolongations of the rise time beyond 3 cycles of probe frequency yielded little improvement in Q10, low cut-off slope and high cut-off slope. 2) Q10, low cut-off slope and high cut-off slope for normal-hearing subjects increased gradually with the increase in stimulus frequency or the decrease in stimulus pressure. Maximum masker frequency of the tuning curves was not always equal to the frequency of probe without the 2-kHz. For the 0.5, 1kHz probe, the maximum masker frequency of the tuning curves showed higher values than the frequency of probe. For the 4kHz probe, the maximum masker frequency of the tuning curves showed lower values than the frequency of probe. The results indicate that the tone pip stimuli will allow to assess certain conditions of auditory function at different frequencies, and they show wider frequencies' spread in the cochlea area near stimulus frequencies. 3) For subject with abrupt high-frequency hearing loss (30dB/oct), a pronounced down-ward shift of maximum masker frequency, down-ward shift of high cut-off slope and up-ward shift of low cut-off slope were found when the probe was placed in the region of elevated threshold. For subject with low-frequency hearing loss (25dB/oct), a pronounced up-ward shift of maximum masker frequency, down-ward shift of low cut-off slope were found. Maximum masker frequency, low and high cut-off slope of hearing impaired subjects were not always equal to those of normal subjects for same probe. Especially the value of the maximum masker frequency shifted to the direction in which the most sensitive frequency was observed in audiogram. The threshold of ABR reflected the cochlea function of the most sensitive area near stimulus frequencies. Greatest predictive error was observed in steeply sloping audiograms. PMID- 2593039 TI - [Automatic boundary detection and pathological diagnosis of the maxillary sinus]. AB - A method for automatic boundary detection of the maxillary sinus from a cranial X ray radiograph has been developed. An algorithm using the local segmental properties of the X-ray image to transform a continuous tone image into a bi level image is introduced. In addition, the global shape information such as the area, the perimeter, and the complexity, are considered for the boundary detection. The boundary of the maxillary sinus detected by this method coincided precisely with the area plotted-by experienced otolaryngologists. Furthermore, the cumulative distribution function (CDF) calculated from the density histogram of the maxillary sinus has been employed to perform the tonal evaluation of the intra-maxillary pathological changes. The distance between the CDFs successfully demonstrated the difference in pathological stages of the chronic sinusitis. PMID- 2593038 TI - [A study on three components of auditory evoked brainstem response]. AB - Under adequate stimulus intensities, the power spectra of normal auditory evoked brainstem responses (ABR) are mainly composed of three major parts, i.e. component A (0 approximately 350Hz), B (350-700Hz). and C (700-1200Hz). By means of digital filter using fast Fourier transform, three derived ABR waveforms consist of each component of the power spectrum were obtained and named component waves A, B, and C, respectively. For the purpose of discussing the possibilities of clinical use of derived ABR waveforms, these three component waveforms were analized in normal hearing subjects and patients with central disorders. In addition, the changes of these waveforms were studied in a series of lesion experiments of brainstem auditory pathway in cats. Before and after destructions of cochlear nerve, cochlear nuclei, superior olivary nuclei, lateral lemniscus and inferior colliculus, these three derived waveforms were compared. The following results were obtained: 1) In normal subjects, the changes in ABR waveforms according to the changes of the rise-time, interstimulus interval and frequency of the stimulus were mainly attributed to component wave C. 2) In patients with central disorders, component wave C were initially affected. Therefore, it seemed that the earliest waveform alterations in ABR occur in high frequency parts of the power spectrum. 3) The resultant experimental data in cats indicated that component wave C seems to be the most sensitive to reveal the lesion sites. 4) It was suggested that the analysis of ABR by three component waveforms was useful to detect the neurological disorders. PMID- 2593041 TI - [Classification and surgical repair of congenital ear lobe anomalies]. AB - We encountered 21 cases of congenital ear lobe anomalies at our clinic during the past seven years. This report presents our system for classification of these cases and describes some typical cases. We divided ear lobe anomalies into four groups according to the type of lobe as follows; large, adhesive, defective and cleft ear lobe type. In the large lobe type, the ear lobe is characteristically large. For the adhesive lobe type, no angle is formed between the ear lobe and the face, i.e. the helix is elongated in a straight line towards the face. The cleft ear lobe type is classified into two surgical categories, viz. the cleft and appendage types. The former is recognized by a cleft on the lobe which continues from the helix, whereas the latter type has an appendage on the lobe. Combinations of these two types are included in the cleft type because a cleft in the lobe is more significant in terms of the shape of the repaired ear lobe. As regards the surgical repair of these anomalies, careful consideration is required in order to accomplish tridimensional reconstruction and create the natural curve of the lobe using z-plasty and other local flaps. PMID- 2593040 TI - [Anatomical study of the superior jugular bulb by use of high-resolution computed tomography]. AB - Using high-resolution computed tomography, the relationship between the superior jugular bulb and the tympanic cavity was analysed in 40 subjects. Until now, the superior jugular bulb was thought to lie below the floor of the hypotympanum, however, the following observations were made from this study: 1) In 48 (60%) out of 80 temporal bones (40 cases), the top of the superior jugular bulb was situated in the higher level than the floor of the hypotympanum. 2) In 9 cases, the jugular bulb was separated from the tympanic cavity by only thin bony wall. This finding was noticed on the right side in 8 cases and was bilateral in a case. 3) In 21 cases (52.5%), the right jugular bulb was situated in higher level than the left, and the reverse finding was noticed only in 4 cases (10.0%). The reason why the right jugular bulb is frequently higher than the left was thought to be related to its function. Namely, the jugular bulb is useful to absorb the pulsation of the carotid artery, therefore, it was considered that the anatomical and physiological differences between the right and left carotid arteries induce the asymmetry of the jugular bulbs. PMID- 2593042 TI - [Distribution of retinal ganglion cells projecting into the nucleus of the optic tract in the rat]. AB - Recent neurophysiological studies have disclosed that the nucleus of the optic tract (NOT) in the pretectum is the first relay station responsible for horizontal optokinetic nystagmus (OKN) both in non-foveate and foveate animals. However, what parts of the retina and what kinds of retinal ganglion cells project their fibers into the NOT have been controversial. In the present study, horseradish peroxidase conjugated with wheatgerm agglutinin (WGA-HRP) was injected into the NOT of rats. The retina and injection sites were processed for the histochemical demonstration of WGA-HRP in order to investigate the distribution of the retinal ganglion cells projecting into the NOT. The present study indicated that visual signals responsible for OKN are mainly conducted from the contralateral retinal ganglion cells, and only from the ventral area of the ipsilateral retina. The retinal ganglion cells projecting into the NOT ipsilateral to the injection site were larger than those on the contralateral side. Large retinal ganglion cells existed on the peripheral areas including ipsilateral ventral area. The density of the ventral ganglion cells of the retina contralateral to the injection site was lower than that in other areas of retina, and the density of the ventral ganglion cells ipsilateral to the injection site tented to be greater than that on the contralateral side. Since the ventral area of retina corresponded to the upper visual field in front of the nose, it may receive visual signal of OKN and fire OKN. In conclusion, visual signals responsible for OKN are conducted through the retinal ganglion cells mainly contralaterally, and only from the ventral area of the retina ipsilateral to the injection site. PMID- 2593043 TI - Morphological and functional characteristics of myocytes isolated from human left ventricular aneurysms. AB - Isolated single myocytes were prepared from myocardium of developing ventricular aneurysms and from myocardium within the scar of chronic ventricular aneurysms. The morphology and function of the individual cells were compared. The cells from developing aneurysms were rod-shaped, with a distinct sarcomeric structure, but did not contract even in the presence of high calcium concentrations. The sarcomere length was significantly higher than that of cells from chronic aneurysms and approached the theoretical point at which no contraction can occur. Cells from chronic aneurysms were either rod-shaped and contractile, or rounded due to hypercontracture of the myofilaments. Electron microscopy of cells from developing aneurysms confirmed the presence of elongated sarcomeres, a loss of the actin-myosin interdigitation, and damage to the contractile proteins which was particularly evident in the thin filaments. Cells with similar characteristics have also been isolated from a ruptured, ischaemic papillary muscle. These changes, which are due either to ischaemia or to overstretching of cells, may account for the weakness of the wall of developing aneurysms and be a cause of rupture or enlargement. PMID- 2593044 TI - Carcinoma in situ of the testis in infertile men. A histological, immunocytochemical, and cytophotometric study of DNA content. AB - Of 723 infertile men (128 with a history of cryptorchidism) whose testes were biopsied at the outer lateral face of the testis, five presented carcinoma in situ (CIS) in one testis. These testes were removed, serially sectioned, and examined by light microscopy. In order to evaluate whether only one or two biopsies are sufficient to diagnose CIS, before sectioning the testes four biopsies were taken at the anterior face, posterior face, superior pole, and inferior pole of the testis, respectively. Two of the five men had undergone orchiopexy in infancy and the testis contained tubules with Sertoli cells and isolated spermatogonia. CIS was also present in some tubules that were principally located near the rete testis. Of the four simulated biopsies, only that performed at the posterior face of the testis revealed CIS. The other three infertile men showed tubules with complete, although reduced, spermatogenesis, and tubules lined by Sertoli cells only. CIS was found in both types of tubules. These tubules with CIS formed lobules that extended throughout the testicular parenchyma. Most simulated biopsies performed in these three testes showed CIS. The average nuclear DNA content of CIS cells was about 4c in all testes. This content was similar both in tubules with complete spermatogenesis and in tubules with Sertoli cells only. PMID- 2593045 TI - Prognostic significance of activation and differentiation antigen expression in B cell non-Hodgkin's lymphoma. AB - Immunophenotyping shows heterogeneity of expression of activation and differentiation antigens in B-cell non-Hodgkin's lymphoma (NHL). To investigate whether antigen expression correlates with clinical behaviour we have studied the clinical presentation and follow-up of a series of 111 B-cell lymphomas previously phenotyped for a panel of antigens including CD groups 5, 9, 10, 21, 23, 25, 30, 38, 4F2 antigen, and transferrin receptor. CD antigens 5, 10, and 23 were expressed significantly more often by low grade lymphomas whereas CD38, 4F2 antigen, and transferrin receptor were more often expressed by high grade lymphomas. There was a significant correlation with survival and age, stage at presentation, histological grade, and expression of 4F2 antigen and transferrin receptor but not with the other antigens studied. 4F2 antigen and transferrin receptor may identify a poor prognostic group of cases in low grade lymphoma but we conclude that phenotyping B-cell NHL for many of the antigens expressed at various stages of B-cell differentiation and activation does not provide clinically useful information in addition to that obtained from standard histological classifications. PMID- 2593046 TI - Sudden death in childhood and adolescence. AB - Sudden natural deaths of individuals between the ages of 2 and 20 years which occurred during a 20-year period were identified from mortuary records. Necropsy reports and histological sections were reviewed; 169 sudden natural deaths were identified amongst 1012 deaths in that age group. Ninety-two sudden deaths occurred to children with recognized disorders; congenital heart disease, asthma, and epilepsy were the commonest problems identified. Amongst the 77 deaths of apparently healthy children, infection was the most frequently recognized disease. Only 11 deaths were unexplained, comprising 1 per cent of the necropsy population or 6.5 per cent of sudden natural deaths, a much smaller proportion than pertains in infancy. Necropsy examination of children dying suddenly yields useful information. PMID- 2593047 TI - Cellular and humoral immune responses in Campylobacter pylori-associated chronic gastritis. AB - Gastric cellular and humoral immune response investigated by immunoperoxidase staining of 53 antral biopsies showed significant differences in Campylobacter pylori-associated gastritis as compared with non-bacterial chronic gastritis and normal controls. IgA, secretory component, and complement C3 coated bacilli were seen in all cases of active chronic gastritis. C3 was always associated with coating by IgA, IgM, or both, which were rarely seen in gastritis without polymorphonuclear neutrophil infiltration. Intraepithelial mononuclear cellular infiltration was seen in 18 of 26 cases of C. pylori-associated chronic gastritis. The intraepithelial mononuclear cells stained positively for T cells and histiocytes. PMID- 2593048 TI - Abnormal alveolar epithelial repair associated with failure of resolution in experimental streptococcal pneumonia. AB - We describe an experimental model in Wistar rats of non-resolving bronchopneumonia evoked by Streptococcus pneumoniae type 25. In contrast to a model of resolving streptococcal pneumonia that we have previously described, morphological studies reveal that in this model, there is significant early damage to type 1 pneumocytes which progresses to necrosis, leaving isolated areas of denuded alveolar basement membrane. Furthermore, there is accompanying degeneration and necrosis of a proportion of the type 2 pneumocytes, and alveolar epithelial repair by proliferation and differentiation of these cells appears to be retarded. Isolated, hypertrophic, and hyperplastic foci of type 2 pneumocytes persist as the acute inflammatory response subsides, and organization progresses with proliferation and emigration of fibroblasts into the lumina of alveoli and terminal bronchioles. The resultant lesion is morphologically indistinguishable from bronchiolitis obliterans organizing pneumonia. We hypothesize that the abnormal outcome in this model of pneumonia is a consequence of the failure of proliferating type 2 pneumocytes to transform into type 1 pneumocytes and thus maintain the integrity of the alveolar epithelial surface. PMID- 2593049 TI - Animal model of margosa oil ingestion with Reye-like syndrome. Pathogenesis of microvesicular fatty liver. AB - The aetiology and pathogenesis of Reye's syndrome (RS) are incompletely understood. A number of environmental toxins and biological agents, including viruses, have been postulated to cause RS, either acting alone or synergistically. Most investigations have suggested that the primary insult is in the liver mitochondria, leading to a complex biochemical catastrophe, with death from encephalopathy. Margosa oil (MO), a long-chain fatty acid compound, has been shown to cause a Reye-like syndrome with death from hepatoencephalopathy, in children in Malaysia and India. The present time-course study performed in MO administered mice showed the development of hepatic lesions with many features of RS. MO acts rapidly, within 30 min, on the nuclei of hepatocytes inducing mitoses and binucleated cells. This is followed by mitochondrial injury, with swelling, rarefaction of matrix, loss of dense bodies, pleomorphism, and loss of ribosomes starting at 60 min. There is loss of liver glycogen, and proliferation and hypertrophy of the endoplasmic reticulum (ER), followed by the presence of lipid droplets in the hyaloplasm, and globules within dilated cisterns of the ER. Additional fatty acids from lipolysis of body adipocytes, and fat globules from intestinal MO ingestion further aggravate the liver fatty change. There is evidence of fat globule ingestion by endocytosis into hepatocytes at the level of the sinusoids. The development of microvesicular liver steatosis and glycogen depletion due to involvement of liver cell organelles occur rapidly as in RS. PMID- 2593050 TI - Emergency separation of omphaloischiopagus tetrapus conjoined twins in the newborn period. AB - This article reports an experience on subemergent separation of xyphoomphaloischiopagus tetrapus conjoined twins in the newborn period when survival of one of the twins was threatened by a severely malformed counterpart. PMID- 2593051 TI - Studies on intestinal motility and mechanism of cholangitis after biliary reconstruction. AB - Cholangitis is a serious complication of biliary reconstruction for congenital biliary atresia. To observe the effect of intestinal motility on the mechanism of cholangitis, we studied intestinal motility in dogs after experimental common duct ligation and reconstruction by Roux-en-Y or interposition cholecystojejunostomy. One year after operation, bipolar electrodes were implanted in the canine intestine and electromyograms were performed. Distinct patterns of propagation and the direction of intestinal motility characteristic of each procedure were observed. The animals with Roux-en-Y loops showed a decrease in motility of the duodenum and upper jejunum. Those with an interposed segment demonstrated stagnation in both the duodenum and jejunum, and poor coordination of intestinal movement. The myoelectric activity of the Roux-en-Y loop suggests that it is the reconstruction technique most likely to prevent reflux cholangitis. PMID- 2593052 TI - Perioperative change of plasma endotoxin levels in early infants. AB - As a preliminary study to elucidate the relationship of endotoxemia to postoperative morbidity, the plasma endotoxin levels in 64 surgical neonates were quantitated by the chromogenic limulus test (Toxicolor test; Seikagaku Kogyo, Tokyo, Japan). The preoperative levels of plasma endotoxin were 64 +/- 59 pg/mL in the group of infants with perforated peritonitis (n = 9), 63 +/- 51 pg/mL in the group of infants with gastroschisis (n = 7), and 15 +/- 16 pg/mL in the group of infants with ileus (n = 28), while the mean level was 6 +/- 5 pg/mL in the remaining 20 surgical neonates who had no signs of ileus or peritonitis. In the serial determination of plasma endotoxin in 28 neonates, the levels on the first postoperative day increased significantly compared with the preoperative levels (16 +/- 18 pg/mL to 46 +/- 25 pg/mL, P less than .01). They decreased gradually to 8 +/- 5 pg/mL within a week in 15 neonates who had no postoperative complications. However, in 13 neonates who had postoperative complications such as wound infection or postoperative ileus, the postoperative levels of plasma endotoxin increased to a much higher level and remained there. In this article the relationship of clinical endotoxemia to postoperative thrombocytopenia and hyperbilirubinemia is analyzed, and the usefulness of evaluating endotoxemia in surgical neonates is discussed. PMID- 2593053 TI - Renovascular hypertension in children: current concepts in evaluation and treatment. AB - Since 1981, we have evaluated and treated 22 children with renovascular hypertension (RVH). Seventeen patients had stenosis of their native renal arteries, and five had stenosis of the artery in a transplanted kidney. RVH was caused by fibromuscular dysplasia in 13 patients, by trauma in 2 patients, and by arteritis in 2 patients. Among the patients who had transplanted kidneys, three had technical causes for stenosis and two had stenosis due to rejection. The disease was unilateral in 10 patients, bilateral in 5, and present in a solitary kidney in 7, including the five renal transplants. Diagnostic studies that strongly suggested the presence of renovascular disease were an initial diastolic blood pressure greater than 100 mm Hg, an elevated peripheral vein renin activity level, and an abnormal renal scan if the patient's hypertension was being controlled with an angiotensin-converting enzyme inhibitor (ACEI). Only the renal arteriogram was 100% accurate in confirming the presence of RVH. Percutaneous angiographic correction was attempted in 13 patients and resulted in lasting improvement of the hypertension in five (38%). Surgical revascularization was attempted in 17 children, including the 8 with failed angioplasty, with improvement or cure of the hypertension in 15 patients (88%). Combining percutaneous transluminal angioplasty (PTA) and surgical results gave 20 of 22 patients (91%) with cure or improvement of their hypertension. Four of 27 affected kidneys (15%) could not be revascularized and were removed. We conclude from this series of patients that despite improvements in noninvasive studies, renal arteriogram remains the only study that is 100% accurate in evaluating children for RVH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593054 TI - Congenital intrinsic duodenal obstruction: problems in the diagnosis and management. AB - Nineteen infants with intrinsic duodenal obstruction are analyzed. Atresia was the most common lesion. An exceptionally high rate of associated anomalies (73.7%) were present; Down's syndrome, the single most common anomaly, was seen in 47% of the infants. In seven infants, the diagnosis was delayed and in another three it was made intraoperatively while establishing a gastrostomy for esophageal atresia. Three infants died without operation because of gross prematurity and multiple anomalies. Of the 16 operated on, three died, one due to peritonitis and the other two because of metabolic derangements. Of the various operative procedures used, no significant difference was found in the final outcome of treatment. A schematic approach to the diagnosis and management is proposed. PMID- 2593055 TI - The significance of alkalosis and hypochloremia in hypertrophic pyloric stenosis. AB - Hypochloremic alkalosis is the "classical" electrolyte abnormality seen in hypertrophic pyloric stenosis (HPS), yet it occurs in only about half the patients. To define the clinical differences between infants who were alkalotic or hypochloremic and those who were not, we reviewed the records of 216 patients treated for HPS over a recent 5-year period at our institution. The 202 patients who had a full set of serum electrolytes drawn on admission were divided into nonalkalotic and alkalotic bicarbonate groups A (less than or equal to 25 mEq/L, n = 105) and B (greater than 25 mEq/L, n = 97) and also nonhypochloremic and hypochloremic chloride groups A (greater than or equal to 99 mEq/L, n = 117) and B (less than 99 mEq/L, n = 85). The alkalotic group B had a significantly higher proportion of black patients (17.5% v 8%), longer mean duration of illness (17.8 v 9.4 days), higher incidence of palpable pyloric mass (97% v 82%), greater degree of dehydration, lower mean serum sodium (136.3 v 137.7 mEq/L), lower mean serum potassium (4.50 v 5.15 mEq/L), and lower mean serum chloride (92.4 v 102.3 mEq/L) than did the nonalkalotic group A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593056 TI - Experimental small-bowel transplantation: alternative strategies for graft prolongation. AB - Alternative combined immunosuppressive therapy was tested in canine orthotopic bowel transplantation. Despite sporadic long-term survival, cyclosporine is still questionably effective. Triple-drug therapy (cyclosporine, azathioprine, and prednisone) combined with antilymphocyte serum or with a short segment graft was effective in reducing the early postoperative mortality due to acute rejection but did not alter the long-term survival rate. There was no apparent relationship between the serum cyclosporine levels and survival. The long-term survivors (longer than 100 days) maintained relatively low serum trough levels of cyclosporine. These suggest that orthotopic bowel transplantation in the dog, and probably in the human as well, requires improved immunosuppressive regimens. PMID- 2593057 TI - Autonomic innervation of the intestine from a baby with megacystis microcolon intestinal hypoperistalsis syndrome: I. Immunohistochemical study. AB - A typical case of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is reported. The patient, an infant girl, was fed only by total intravenous nutrition and is now 3 years old. The distribution of several gut peptides was examined in the resected small intestine using an immunohistochemical method. Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM)-containing nerve fibers were decreased; however, substance P- and leucine enkephalin (Leu-ENK)-containing fibers were increased. The imbalance between several kinds of gut peptides might be one the causes of aperistalsis in MMIHS. This is the first report about the gut peptides of MMIHS. PMID- 2593058 TI - Autonomic innervation of the intestine from a baby with megacystis microcolon intestinal hypoperistalsis syndrome: II. Electrophysiological study. AB - The pattern of spontaneous activity and innervation of the stomach, small intestine, and bladder obtained from a patient with megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) was studied in vitro, using tension recording and microelectrode techniques. We found that, compared with findings in the controls, autonomic inhibitory input to the smooth muscle cells of the small intestine was significantly decreased. PMID- 2593059 TI - The pathophysiology of Hirschsprung's-associated enterocolitis: importance of histologic correlates. AB - To more clearly define the pathophysiology of Hirschsprung's-associated enterocolitis (HAEC), this study comprehensively evaluates the gastrointestinal tissue of a group of infants with clinical HAEC. A pathologic grading system that demonstrates a progressive sequence of histologic changes specific for HAEC is established. The grading system correlates closely with clinical enterocolitis and may prove to be a useful method for early detection of infants at risk for the development of clinical HAEC. A significant alteration of intestinal mucins with an increase in neutral mucins and a decrease in acidic-sulfomucins was identified in HAEC tissue specimens. Enterocyte-adherent organisms were present in 39% of HAEC tissue specimens. The pathogenesis of HAEC may result from an alteration in intestinal mucins that may allow for the subsequent adherence of enteropathogenic organisms to enterocytes. The enterocyte-adherent organisms have the potential to induce an enterocolitic process and may contribute to both the intestinal and systemic manifestations of HAEC. PMID- 2593060 TI - The influence of HLA matching on renal allograft survival at a single pediatric center. AB - Between January 1, 1969, and February 2, 1988, 331 pediatric renal transplants were performed at a single pediatric center. Of these 225 were first cadaveric allografts. Graft allocation was independent of the outcome of human lymphocyte antigen (HLA) matching. The results of class I antigen matching were analyzed in 224 transplants, and actuarial graft survivals were calculated. Class II antigen matching was analyzed in 80 patients from January 1, 1982, and submitted to the same analysis. HLA matching could not be demonstrated to be beneficial. It is proposed that any matching benefit is small and obscured in our series by the dominance of other factors. PMID- 2593061 TI - Augmentation cystoplasty in patients with exstrophy-epispadias. AB - In a series of over 200 patients with exstrophy-epispadias from the Mayo Clinic, a subgroup of 11 with small bladder capacities, decreased detrusor compliance, and urinary incontinence underwent augmentation cystoplasty. Preaugmentation bladder capacities were between 25 and 250 mL (mean, 73 mL). Bladder capacities after enterocystoplasty improved significantly, with a range between 180 and 500 mL (mean, 355 mL). Ten of the 11 patients have total urinary continence for greater than 3 hours. One child remains dry between 1 1/2 and 2 hours. Nine patients are in complete urinary retention and are managed by clean intermittent catheterization. Two patients void spontaneously by pelvic muscle relaxation and abdominal straining alone. All patients maintain normal or stable renal function postoperatively. Excretory urography showed decreased caliectasis in two patients with preoperative hydronephrosis and stable upper urinary tracts in nine patients. Enterocystoplasty can produce total urinary continence, preserve renal function, and avoid the long-term sequelae of urinary diversion in selected children born with exstrophy-epispadias. PMID- 2593062 TI - Testicular oximetry: a new method for the assessment of tissue perfusion and viability following torsion and detorsion. AB - This study evaluated the use of a polarographic surface PO2 electrode to assess testicular perfusion and viability following torsion and detorsion. Adult male Sprague-Dawley rats were divided into groups and subjected to unilateral testicular torsion and detorsion of varying degrees and durations. Rats subjected to sham torsion or 720 degrees torsion did not show significant decreases in testicular PO2 after 15 minutes, whereas those subjected to 1,080 degrees torsion or spermatic cord ligation uniformly decreased their testicular PO2 to 0 mm Hg within 10 minutes. Testicular PO2 values were similar in rats subjected to 60 minutes of 720 degrees torsion followed by detorsion and those undergoing 15 minutes of 1,080 degrees torsion and detorsion. Rats subjected to breathing 100% oxygen uniformly increased their testicular PO2 to an average of more than twice room-air values. However, rats subjected to 1,080 degrees torsion for 6 hours followed by detorsion did not increase their testicular PO2 when subjected to breathing 100% oxygen, whereas those subjected to 720 degrees torsion for 6 hours followed by detorsion did increase their testicular PO2 when subjected to breathing 100% oxygen. The latter rats did not show microscopic changes associated with acute testicular infarction, whereas the former did.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593063 TI - Testicular enlargement as a presenting feature of monocytic leukemia in an infant. AB - Acute monocytic leukemia is uncommon and unusual in its propensity to present with extramedullary involvement. We describe testicular enlargement in an infant as the presenting feature of this disease. PMID- 2593064 TI - Angiomyolipoma causing life-threatening hematuria in a child with tuberous sclerosis. AB - A case of a 12-year-old boy with tuberous sclerosis who developed life threatening hematuria is presented. An angiomyolipoma of the lower two thirds of the left kidney resulted in a tumor hemorrhage that was successfully treated by partial nephrectomy. PMID- 2593065 TI - Intralesional steroid injection in the management of esophageal stricture. PMID- 2593066 TI - Early correction of posterior crossbite: biomechanical characteristics of the appliances. PMID- 2593067 TI - DNA probe detection of key periodontal pathogens in juveniles. AB - Recognition of juvenile forms of periodontitis have been shown to be directly linked with specific Gram-negative rods, primarily Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius. However, clinical application of these laboratory findings have generally been restricted to the research environment. The purpose of this study was to explore the relationship of these three pathogenic species in children using the reliable and accurate new technology of DNA probes. Results indicated that the pathogenic oral flora did not differ significantly between subjects with and without gingival inflammation. Therefore, tracking of pathogens using clinical parameters of inflammation are unreliable and accurate monitoring requires microbiological testing in order to properly identify the presence or absence of pathogens. PMID- 2593069 TI - Dental health status in 7-year-old children: a basis for mineralizing therapy. AB - Initial dental health status of permanent teeth among 584 children aged seven years selected for clinical trial with mineralizing agent, Remodent in Varkaus (Finland) and in Moscow (U.S.S.R.) was described and analyzed. These results were compared systematically with those reported previously for the same age groups from the different data. The similarity in patterns of occurrence of EFD lesions and caries and differences in their prevalences between children in the two ethnic groups remained the same. Differences in prevalence of EFD lesions cannot be explained as due to the influence of local branches of Public Dental Health systems (influence on oral hygiene habits and use of fluorides). Differences in prevalence of caries may be explained as being due to the influence of local branches of Public Dental Health systems (use of sealants). The cariogenic situation, measured as a number of EFD lesions, and the activity of these lesions on the smooth surfaces of permanent teeth also remained constant over time. This indicates a need for active caries prevention among children in both ethnic groups. PMID- 2593068 TI - Sequelae of trauma to the primary dentition. AB - A total of 69 traumatized maxillary primary incisors were followed to determine the sequelae of trauma. At initial presentation, discoloration was the most common presenting sign of trauma (30.4%), followed by crown fractures (21.8%) and displacement of the teeth (15.9%). The affected teeth were treated by routine clinical procedures. In the 11 teeth showing crown fractures, over 90% were normal at the first follow-up visit with a mean of approximately 27 weeks, but 2 more became necrotic at later recall periods. In contrast, displacement injuries were associated with greater incidence of pulpal necrosis with nearly half of the affected teeth showing periapical radiolucencies after a mean follow-up period of 44 weeks. Similarly, nearly half of the teeth affected by discoloration showed radiographic evidence of pulpal pathology after a mean recall period of 44 weeks. This study shows that a high proportion of traumatized primary incisor teeth eventually become necrotic and the need for continual supervision of all injured primary teeth is stressed. PMID- 2593070 TI - Lateral periodontal abscess in a child. PMID- 2593071 TI - What price success: can we afford "saved" babies? PMID- 2593072 TI - A model outreach program for health care screening. AB - The outreach program described here provides health care screening in an inner city clinic to children and adolescents who attend any organized program in the community. The objectives are (a) to provide low-cost, accessible health care screening and (b) to provide health education. The program is supervised by a pediatric nurse practitioner who works closely with an administrative assistant, an office associate, and other clinical staff members. In the academic years 1986 1988, 668 children and adolescents were screened. Abnormal patient findings identified by the outreach program were similar to those reported from other studies. The conclusions from this program's efforts are that outreach health care screening programs are effective in evaluating the health status of children and adolescents in communities. PMID- 2593073 TI - Hepatitis B virus infection in Southeast Asian children. AB - Since the end of the war in Vietnam, approximately 850,000 Southeast Asian refugees have come to the United States. They present a challenge for health care providers because of language and cultural differences that can create barriers to effective health care. Nurse practitioners who work with Southeast Asian refugees should be aware that hepatitis B virus (HBV) infection is highly endemic in Southeast Asia, and the virus is most commonly transmitted during the perinatal period or during childhood. HBV infection can cause acute hepatitis B, chronic hepatitis, cirrhosis, and primary hepatocellular carcinoma and is associated with considerable morbidity and mortality. Susceptible children and infants born to mothers who are hepatitis B carriers should be vaccinated with the hepatitis B vaccine. Vaccination can prevent the serious sequelae of HBV in a high percentage of the pediatric population. PMID- 2593074 TI - Primary health care for deaf children. Part I. PMID- 2593075 TI - Ambiguous genitalia. PMID- 2593076 TI - Breast-feeding aids. PMID- 2593077 TI - 1988 NAPNAP membership survey: characteristics of members' practice. AB - In 1988 the characteristics of the 2560 members of NAPNAP were determined by means of a mailed survey. Approximately 52% of the members returned usable questionnaires. Members were asked for information about their educational preparation, demographic characteristics, and professional employment status. Data about members' practice, how their practice has changed over time where possible, and implications for the future are reported. PMID- 2593078 TI - The Second World Symposium: Computers in the care of the mother, fetus and newborn. Kyoto, Japan, October 23-26, 1989. Abstracts. PMID- 2593079 TI - Intracellular glutathione levels in human colon cancer cells naturally resistant to cross-linking agents. AB - Correlation between sensitivity to two cross-linking agents, 1-(4-amino-2 methylpyridine-5-yl)-methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) and cisplatin (DDP), and intracellular glutathione (GSH) level was investigated for two naturally drug-resistant human colon cancer cell lines in comparison with two drug-sensitive human leukemia cell lines. As a result, no appreciable correlation was observed between them. We also studied the possibility that DL-buthionine-S,R sulfoximine (BSO), an inhibitor of GSH biosynthesis, can sensitize the cancer cells to these anticancer agents via depletion of intracellular GSH. It was found that BSO potentiated ACNU cytotoxicity against human leukemia K562 cells and DDP cytotoxicity against K562 and human colon cancer WiDr cells. It indicates that cancer cells with higher GSH level are more effectively sensitized by BSO regardless of degree of their intrinsic sensitivity to these anticancer agents. These results suggest that intracellular GSH level is not a common mechanism for natural resistance to cross-linking agents in human colon cancer cells but one of the determinants of sensitivity to these anticancer agents of GSH-rich cells. PMID- 2593080 TI - Structure-activity relationships of phenylethylamine analogs in their serotonergic depressant effects on the spinal monosynaptic reflex in rats. AB - The effects of 2-phenylethylamine (PEA) and related compounds on the spinal monosynaptic reflex (MSR) were examined using C1-spinalized rats. At low doses, PEA, S(+)-amphetamine, S(+)-methamphetamine and phentermine increased the amplitude of the MSR, whereas high doses of these drugs reduced it. p-Substituted PEA analogs (p-C1-PEA, p-methoxy-PEA and (+/-)-p-C1-amphetamine) only reduced the MSR. Low doses of PEA-related rigid compounds, R(+)-2-aminotetralin, (+/-)-N methyl-2-aminotetralin and (+/-)-N,N-dimethyl-2-aminotetralin only reduced the MSR. S(-)-2-Aminotetralin did not affect the MSR. Depressions of MSR produced by PEA, S(+)-methamphetamine and R(+)-2-aminotetralin were antagonized by ketanserin and haloperidol which have 5-hydroxytryptamine (5-HT) antagonistic activity, and the MSR depression caused by S(+)-methamphetamine but not PEA and R(+)-2 aminotetralin was abolished by intracisternal 5,6-dihydroxytryptamine treatment or chronic spinal transection. These results suggest that PEA-related compounds cause MSR depression by direct and indirect 5-HT agonistic mechanisms, and support the proposal that the PEA moiety which exists in R(+)-2-aminotetralin is important for the direct 5-HT agonistic activity of some hallucinogens. PMID- 2593081 TI - Disposition of phenacetin in rabbits pretreated orally and intraperitoneally with 3,4-benzpyrene. AB - Disposition of phenacetin (PHT) administered intravenously was investigated in rabbits pretreated orally and intraperitoneally with 3,4-benzpyrene. 3,4 Benzpyrene pretreatment intraperitoneally 24 and 48 h before the disposition experiments resulted in enhanced PHT metabolism as was shown from the decreased levels of PHT and the increased levels of acetaminophen sulfate (NAPAS) in the blood after intravenous administration of PHT. Following the oral pretreatment with 3,4-benzpyrene 24 h before the disposition experiments, no effect was found on the metabolism of PHT compared to the control. 3,4-Benzpyrene pretreatment orally 48 h before the disposition experiments resulted in enhanced PHT metabolism as was shown from the decreased levels of PHT and the increased levels of acetaminophen glucuronide and NAPAS in the blood. From these results, the response to oral and intraperitoneal pretreatment with 3,4-benzpyrene appears to be profoundly different. A technique for selective enzyme induction in the intestine by the route of administration of inducer is discussed. PMID- 2593082 TI - Kinetic interaction between theophylline and a newly developed quinolone, NY-198. AB - The effect of a newly developed quinolone, NY-198, on the pharmacokinetics and metabolism of theophylline was investigated under steady-state conditions in six male healthy volunteers, in a crossover fashion. A sustained-release theophylline formulation (200 mg twice daily at 12 h intervals) was received as monotherapy or coadministration with NY-198 (200 mg twice daily at 12 h intervals). No significant change in the pharmacokinetic parameters of theophylline was observed during coadministration of NY-198. No significant change in urinary excretion of theophylline and its metabolites was also observed. These findings indicate that NY-198 does not influence the pharmacokinetics of theophylline and we can suggest that quinoline derivatives have less effect on theophylline disposition than 1,8 naphthyridine derivatives among quinolones. PMID- 2593083 TI - Binding of hydrochlorothiazide to erythrocytes. AB - Hydrochlorothiazide (HCT) was administered orally to healthy volunteers and intravenously to rabbits. HCT concentrations in plasma (Cp) and erythrocytes (Ce) were determined by a high-performance liquid chromatographic method. Ce was about 9-fold that of Cp 24 h after the administration to volunteers, and 8-fold 6 h after the administration to rabbits. From the results of the in vitro binding study which was done with rabbit erythrocytes, at least the presence of three kinds of binding site for HCT was expected. The first binding site was characterized by extremely high affinity and very low capacity, and was unaffected by acetazolamide, known as a carbonic anhydrase inhibitor. The second one was characterized by medium affinity and medium capacity, and disappeared under the presence of acetazolamide and may be due to the carbonic anhydrase of erythrocytes. The third one was characterized by low affinity, but its binding capacity was extremely high and apparently unsaturable in the HCT concentration range studied (0.5-100 micrograms/ml = 1.68-336 microM). The binding of HCT to erythrocytes seems to be dominated by the second binding site in the therapeutic range (under 1 microgram/ml of plasma). PMID- 2593084 TI - Ischemia-induced changes in brain levels of monoamines and their metabolites of mice and rats: some protective effects of naftidrofuryl. AB - Employing two types of brain ischemic animal models, an attempt was made to evaluate the protective effect of naftidrofuryl as the normalizing effect on the ischemia-induced changes in the brain levels of monoamines and metabolites. 1) During 2 min ligation of both left and right common carotid arteries of mice, dopamine (DA) content alone significantly decreased among three monoamines and four metabolites measured by a high performance liquid chromatography electrochemical detection method. Pretreatment with naftidrofuryl oxalate (45 mg/kg, i.p.) was found to prevent the DA change, but the lower dose (15 mg/kg, i.p.) of the drug or any other drug tested individually (vinpocetine hydrochloride: 2 mg/kg, Ca hopantenate: 0.1 g/kg, citicoline: 0.1 g/kg, i.p.) had no such effect. 2) Infusion of carbon microsphere (500 particles/100 microliters of 20% dextran/1.5 min/rat) into the right internal carotid artery induced various degree of time-dependent changes in the behavior and also in the brain levels of monoamines and metabolites. Embolized rats which otherwise would survive for at least 6 d after infusion, were divided into the lightly-infarcted and severely-infarcted groups by grading the behavioral abnormality. Subsequent treatments with naftidrofuryl oxalate (15 mg/kg, i.p., twice daily, totally 4 times) which was begun 16 h after microsphere injection, was found to accelerate the recovery rate of brain dopamine level once decreased by the embolism though only in the lightly-infarcted group. The significance of the results obtained herein were discussed in relation to the clinical effectiveness of naftidrofuryl in human brain ischemic diseases. PMID- 2593085 TI - Inhibition of the vagal reflex-induced tracheal constriction by psychotropic drugs. AB - We investigated the effects of psychotropic drugs on reflex tracheal constriction in anesthetized, paralyzed, and artificially ventilated mongrel dogs. The tracheal constriction induced by the electrical stimulation of the central cut end of the right vagus nerve was abolished by sectioning both the left superior laryngeal and recurrent laryngeal nerves, and was reduced by a low dose of pentobarbital (3 mg/kg, i.v.). This indicates that the tracheal constriction is mediated by a vagal reflex. Chlorpromazine (3 mg/kg, i.v.) and imipramine (1-3 mg/kg) reduced the reflex tracheal constriction. Chlorpromazine and imipramine had no effect on the tracheal constriction induced by the efferent electrical stimulation of the recurrent laryngeal nerve. This suggests that the higher centers may affect the reflex airway constriction and that the present preparation may be useful for investigating the effect of psychotropic drugs on the reflex airway constriction during asthmatic attacks. PMID- 2593086 TI - Tips on tables. PMID- 2593087 TI - Focus on follower-ship: challenge of the 1990s. PMID- 2593088 TI - Minimizing the risk of blood-borne infection in the PACU. PMID- 2593089 TI - Hepatitis B: the disease, the risk, the answer. PMID- 2593090 TI - Time out: nurturing and healing the health care giver. PMID- 2593091 TI - [Potentiation of deltamethrin toxicity by organophosphorus insecticides]. AB - There is a potential hazard in mixed intoxications by pyrethroids and organophosphate insecticides, due to the fact that low toxicity of pyrethroids on mammals is chiefly due to quick cleavage of molecule by esterases, which can be thwarted by esterase inhibitors. We have developed a method in order to measure the duration and the intensity of potentiation of deltamethrin by a variety of organophosphate compounds. It was demonstrated that some of them (azinphos, dichlorvos, dimethoate, fenitrothion, omethoate) induce an increase of toxicity of deltamethrin. But, the total toxicity of association of Deltamethrin with Dimethoate, Fenitrothion, is weak, and does not prohibit their use. Others (methyl-parathion, acephate, phosphamidon, monocrotophos) have no such effects, even if they have a very high intrinsic toxicity. Cholinesterase inhibitors of the carbamate group are ineffective. It is suggested that the potentiation is mainly in relation with the kinetic of esterase inhibition, which is different, and specific to each organophosphate compound. So, it is essential that a specific toxicological measurement must be performed with any different insecticide, in order to anticipate the danger of a mixed intoxication by pyrethroids and organophosphates. PMID- 2593092 TI - [Paraquat poisoning. Pulmonary lesions]. AB - The preliminary results of a study of the pulmonary histopathological injuries observed in autopsy samples from six paraquat poisoning cases are presented. The pattern of the pulmonary injuries is discussed with regard to the survival time. Twenty-four hours after the ingestion, intense edema of the alveolar walls, congestion, capillary thrombosis and infiltrations of polynuclears in the septa were observed. Areas of ischemic necrosis were also noticed. Four days after the ingestion the histological changes remained. Six days after it was already observed the formation of hyaline membranes. After nine days the histological patterns changed, with thickness and septal fibrosis and residues of hyaline membranes. PMID- 2593093 TI - [Ethical aspects and responsibility of poison control centers]. AB - Reflections on the medical and the responsibility of Poison Centres and on the situations involving ethical questions they are faced within their everyday life. PMID- 2593094 TI - [Responsibility of poison control center physicians]. AB - Rennes's Poison Control Centers as a public medical department associated with an emergency care unit for poisoned patients, is also endowed with a role in toxicological information. In this regard, doctors are working as health officers in the respect of professional ethics. Administrative courts will therefore have to consider suits opposed to poison control doctors. The contract linking the doctor to his counterpart is a benevolence contract. The validity of his oral advice was defined by the Cour de Cassation. The potential evaluation of a fault will be modulated by the particular circumstances of data collection and hence its uncertainty. However, Poison Control Centers must be best organized so that their answers to queries are given by a toxicology-qualified staff. The doctor will also have to provide assistance to those people in danger by adequate help. Despite the ambiguity of some calls which he has to face, the doctor in a Poison Control Center does not seem to be involved by the Law on suicide. PMID- 2593095 TI - [French Society of Toxicology. Paris, February 13, 1989. Abstracts]. PMID- 2593096 TI - The role of stress on the language-independence and code-switching phenomena. AB - This investigation studies the extent to which stress affects the assumed functional separation of coordinate bilingual's linguistic organization. Spanish/English bilinguals were subjects in a GSR linguistic conditioning experiment using two intensities of buzzer sounds (stressful conditions) and two lists of words. One word for each list functioned as the conditioned stimulus. Generalization to semantically, phonemically, and unrelated words occurred in both languages and buzzer conditions. We found a differential impact of the buzzer on the functional separation of the languages, although not in the direction predicted. We concluded that stress produced code-switching, and hence, a primitivization of the subject's cognitive and linguistic functioning is assumed to have occurred. These findings are important in understanding the way stress affects the bilingual's languages at the linguistic and cognitive levels. They are also important in understanding the role of stress in language development and in the transfer of linguistic information. PMID- 2593097 TI - Social and linguistic factors influencing adaptation in children's speech. AB - The ability to appropriately reciprocate or compensate a partner's communicative response represents an essential element of communicative competence. Previous research indicates that as children grow older, their speech levels reflect greater adaptation relative to their partner's speech. In this study, we argue that patterns of adaptation are related to specific linguistic and pragmatic abilities, such as verbal responsiveness, involvement in the interaction, and the production of relatively complex syntactic structures. Thirty-seven children (3-6 years of age) individually interacted with an adult for 20 to 30 minutes. Adaptation between child and adult was examined among conversational floortime, response latency, and speech rate. Three conclusions were drawn from the results of this investigation. First, by applying time-series analysis to the interactants' speech behaviors within each dyad, individual measures of the child's adaptations to the adult's speech can be generated. Second, consistent with findings in the adult domain, these children generally reciprocated changes in the adult's speech rate and response latency. Third, there were differences in degree and type of adaptation within specific dyads. Chronological age was not useful in accounting for this individual variation, but specific linguistic and social abilities were. Implications of these findings for the development of communicative competence and for the study of normal versus language-delayed speech were discussed. PMID- 2593098 TI - Fractures of the femoral neck: a retrospective and prospective study. AB - Fractures of the femoral neck place increasing demands on orthopaedic resources. A retrospective review of 570 cases compared theatre data with Health Board computer records. Only 333 (58%) were appropriately documented, confirming the unreliability of studies based on hospital-generated data. In a prospective study, 582 patients were followed for 3 months. Of those admitted from home, 64% returned to the community; of those walking without a stick before fracture, 20% remained mobile without support after fracture. Poor mobility before fracture was associated with a higher mortality, but mortality was independent of either fracture type or operative procedure. Acute hospital mortality was low at 3.8% but increased throughout convalescence to 18.7% at 3 months. Continuing audit of this expanding group is necessary as a guide for resource allocation, as well as improving clinical standards and comparing results. PMID- 2593100 TI - Management of some common surgical conditions in children: a comparison of practice between surgical units in Edinburgh. AB - Many common surgical conditions in children are managed as day cases by the Paediatric Surgical Service in Lothian but this practice varies within the separate units in Lothian. Five common conditions suitable for day case treatment were looked at during 1987. There was a considerable difference in the time that some conditions were kept in hospital, an orchidopexy, for example, staying for up to 7 days in one unit. The reasons for this difference, the cost implications and the need for future planning of day case surgery is discussed. PMID- 2593099 TI - Bipolar diathermy treatment of long saphenous vein varicosities. AB - A new technique of endoluminal diathermy of the long saphenous vein using a bipolar electrode is described. This is safer than conventional unipolar diathermy and histological examination of the diathermied veins shows similar appearances using unipolar and bipolar diathermy. Clinical assessment of both techniques yields similar results. Endoluminal bipolar diathermy is simple and relatively painless compared with conventional stripping of the long saphenous vein and can be recommended. PMID- 2593102 TI - Third meeting of the Academic Departments of Surgery in Europe. Maastricht, 7-8 April 1989. Abstracts. PMID- 2593101 TI - Small bowel obstruction due to phytobezoars in the intact gastrointestinal tract. AB - We present a series of cases of small bowel obstruction due to an intraluminal phytobezoar concretion. This rare cause of obstruction should not be forgotten as the recent literature has concentrated more on those patients with a past history of gastrointestinal surgery. None of our cases had had previous surgery, highlighting the point that an intact gastrointestinal tract does not exclude phytobezoars as a cause of obstruction. PMID- 2593104 TI - Von Hippel-Lindau disease: preventable morbidity by screening. PMID- 2593103 TI - Irreducible inguinal hernia as a presentation of ruptured abdominal aortic aneurysm. PMID- 2593105 TI - A measured circumcision. PMID- 2593106 TI - Traumatic deaths in the Sheffield and Barnsley areas. PMID- 2593107 TI - Spontaneous rupture of the rectum and colon. PMID- 2593108 TI - Staging laparotomy in early Hodgkin's disease: a surgical view. PMID- 2593109 TI - [Comparison of MRI and CT X-ray in the evaluation of bladder cancer. Apropos of 26 cases]. AB - 26 urothelial carcinomas studied with MRI and CT have been reviewed. The results are connected with surgical and histological data. The assessment of the size and number of tumoral sites is more accurate with MRI, which allows a correct assessment of bladder wall infiltration in 20 of the 22 tumors studied with T2 weighted sequences. The sensitivity of both techniques is the same for the invasion of fat (92%) and the involvement of neighboring organs (67%), although MRI seems to be more specific (85% and 95% for 77% and 89%). The results are similar for the study of lymph node invasion (71% sensitivity). The performances of MRI for the assessment of bladder cancer extension are therefore comparable to those of CT. The advantages of the former technique include the clearer visualization of the tumor itself, especially for cancers of the neck and dome of the bladder owing to exploration in several planes. In addition, it allows a reliable assessment of the degree bladder wall infiltration and differentiates tumors that are not or not very infiltrating from highly infiltrating tumors. PMID- 2593110 TI - [Percutaneous vertebroplasty in the treatment of metastases. Technic and results]. AB - The authors studied 20 patients with vertebral metastases. They injected in these metastases orthopaedic cement by a percutaneous technique under local anesthesis. The results are good for 16 patients, nul for 2 patients and we observed 2 complications. The authors conclude that the best indication is the painy somatic lysis of a vertebra without peri-radicular tumor. PMID- 2593111 TI - [Uncommon aspects of mediastinal teratoma. CT X-ray and MRI study]. AB - CT and MRI features of a multicystic mediastinal teratoma, which was surgically and pathologically confirmed, are presented. CT found 4 cystic tumors of mediastinum with water density content and thick capsule. One kyste contained a fat density area and peripheric calcifications. MRI showed will defined high signal intensity on Spin-echo T1 weighted images. CT and MRI are not reliables in predicting or excluding adherence to adjacent structures. The particularity of this case was the presence of a communication between the anterior right cyst and the posterior left one. This communication passed by the transverse sinus of pericardium. PMID- 2593112 TI - [Rhinopharyngeal craniopharyngioma. CT X-ray and MRI aspects]. AB - The authors report about a rare site of craniopharyngioma, purely extracerebral and located in the sphenoid sinus and the rhinopharynx. No CT or MRI sign is pathognomonic for the lesion, but the presence of a fleshy process containing calcifications and cystic formations must lead to evoking this diagnosis. MRI assesses the extent of the lesions perfectly, but fails to detect small calcifications or ossifications accurately. PMID- 2593113 TI - [Protein-losing enteropathy caused by intestinal metastases of melanosarcoma]. AB - We report about the case of one patient with diffuse small bowel metastases of melanosarcoma, which were revealed by signs of malabsorption 2 years after the exeresis of the initial skin tumor. Metastases of melanosarcoma in the digestive tract, especially the small bowel, have polymorphic and hardly suggestive clinical signs. We lay stress on the high percentage of small bowel metastases of melanosarcoma pointed out by the anatomicopathological literature and on the lack of systematic clinical and radiological search for such metastases in the assessment and follow-up of the primary melanosarcoma. PMID- 2593114 TI - [Value of digital angiography in the preoperative evaluation of arteritis of the leg. Results of a national survey]. AB - The results of a survey on the role of digital angiography in the preoperative assessment of chronic lower limb arteritis demonstrate the diagnostic utility of combining digital image processing and arteriophlebography in a radiological system. This technique allows a practically complete assessment at one go, which is also made possible by the use of small material and of low-osmolarity contrast media, thus reducing the need for extensive anesthesia other than local anesthesia. PMID- 2593115 TI - Characterization of glucocorticoid receptors bound with corticosterone. AB - The physico-chemical properties of glucocorticoid receptors bound with tritiated corticosterone were compared to those of the triamcinolone acetonide glucocorticoid receptor complex. The goal was to determine whether the natural agonist forms complexes similar to those generated by the synthetic agonist. Structure was probed using three techniques; diethylaminoethyl-cellulose (DEAE) chromatography, vertical tube rotor sucrose gradient ultracentrifugation (SGU) and high performance liquid chromatography (HPLC). These techniques are all fast enough to allow analysis of the labile corticosterone receptor complexes. Results showed that complexes generated by both classes of ligands were similar. They eluted from DEAE cellulose and HPLC columns at similar positions and sedimented similarly in sucrose gradients. This was true for both the untransformed and transformed species. It is concluded that natural and synthetic glucocorticoid agonists interact with glucocorticoid receptors to form indistinguishable complexes. Thus synthetic agonists are appropriate probes of events which take place with natural glucocorticoids. PMID- 2593116 TI - Suicide and its prevention. PMID- 2593117 TI - A dilemma in healthcare research. PMID- 2593119 TI - Natal ethnic sign in the Xhosa people. PMID- 2593118 TI - Can suicide and parasuicide be prevented? PMID- 2593120 TI - Management of the Peutz-Jeghers patient. PMID- 2593121 TI - A case of Marshall-Smith or Weaver syndrome. PMID- 2593122 TI - Netherton's syndrome. PMID- 2593123 TI - Benign occipital epilepsy of childhood: a family study. PMID- 2593124 TI - Bilothorax--an unusual problem. PMID- 2593126 TI - Myalgic encephalomyelitis. PMID- 2593125 TI - Overdosage intoxication with cisplatin--a cause of acute respiratory failure. PMID- 2593127 TI - Chronic asthma and hypnotherapy. PMID- 2593128 TI - Newborn circumcision: a long-term strategy for AIDS prevention. PMID- 2593129 TI - TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a tight binding inhibitor of cytochrome P-450d. AB - Based on data indicating that compounds which induce cytochrome P-450d also bind to the enzyme [R. Voorman and S. D. Aust (1987). Toxicol. Appl. Pharmacol. 90, 69 78], we investigated the inhibition of cytochrome P-450d-dependent estradiol 2 hydroxylase by (2,3,7,8-tetrachlorodibenzo-p-dioxin TCDD), using ligand-free cytochrome P-450d from isosafrole-treated rats. Since maximum inhibition of estradiol 2-hydroxylase occurred at TCDD concentrations comparable to the concentration of enzyme (50 nM), a modified form of steady-state kinetic analysis was used. Using I50 = Et/2 + Ki where Et = total enzyme concentration), we showed that TCDD inhibited cytochrome P-450d-dependent estradiol 2-hydroxylase activity with Ki equal to 8 nM. Association of TCDD with P-450d occurred within 2 min of inhibitor addition. Therefore, TCDD can be considered a tight binding inhibitor of cytochrome P-450d. PMID- 2593131 TI - Effects of hyperthermia on xanthine oxidase activity and glutathione levels in the perfused rat liver. AB - The hepatotoxic effects of hyperthermic liver perfusion were investigated in male Fischer 344 rat livers. Perfusions were carried out at 37, 41, 42, 42.5, and 43 degrees C for 2 hr. During the 2 hr, the perfusate was analyzed for activity of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), N-acetyl-beta glucosaminidase (NAG), and glutathione (GSH), oxidized glutathione (GSSG), allantoin, and potassium. After perfusion, each liver was homogenized and analyzed for total xanthine oxidase (XO) activity, percentage type-D and type-O XO, and total GSH content. Perfusate AST, LDH, NAG, and potassium levels were increased significantly with time and were significantly different in all hyperthermic perfusions from the 37 degrees C perfusion values by the end of the perfusion. Perfusate GSH + GSSG levels were increased significantly in all hyperthermic perfusions after 60 min. Liver GSH levels were significantly lowered following perfusion at hyperthermic temperatures. There was a temperature dependent increase in the percentage of XO in the type-O form following perfusion at hyperthermic temperatures, which was strongly and positively correlated with the loss of hepatic GSH. These data support the hypothesis that hyperthermic toxicity to the liver is the result of oxidative stress brought about by conversion of XO to the type-O form. PMID- 2593130 TI - The formation of 2-aminofluorene-DNA adducts in vivo: evidence for peroxidase mediated activation. AB - Formation of DNA adducts in various tissues of dogs fed a single dose of the carcinogen 2-aminofluorene was investigated. Adduct analysis was performed using a technique that allows measurement of both N-(deoxyguanosin-8-yl)-2-amino-2 aminofluorene-DNA adduct formed by reaction of N-hydroxy-2-aminofluorene with DNA, as well as the polar 2-aminofluorene-DNA adducts formed when 2-aminofluorene is activated by prostaglandin H synthase-peroxidase in vitro. Two male beagle (A and B) dogs were examined and a different DNA adduct profile was observed with each dog. For the dog A, N-(deoxyguanosin-8-yl)-2-aminofluorene was the major adduct found in hepatic DNA; no peroxidase-derived adducts were detected in this tissue. In contrast, adducts eluting similarly to peroxidase-derived adducts were found in urinary tract tissues of this dog with the relative abundance of these adducts in the order urothelium greater than renal medulla greater than renal cortex, which correlates with the respective tissues' prostaglandin H synthase activity. N-(Deoxyguanosin-8-yl)-2-aminofluorene was detected in the renal tissues, but not in urothelium. For dog B, only the N-(deoxyguanosin-8-yl)-2 aminofluorene adduct was observed in all tissues examined, including the urothelium. However, total binding to liver, kidney, and bladder were two-, two-, and four-fold lower, respectively, than dog A. These data indicate that both prostaglandin H synthase-mediated activation and N-hydroxylation of 2 aminofluorene occur in vivo and may be subjected to pharmacodynamic considerations. Furthermore, the tissue distribution of the peroxidase-mediated 2 aminofluorene adducts suggests this process may also be of importance in the bladder-specific carcinogenicity of aromatic amines. PMID- 2593132 TI - Nonideal behavior of alkoxyphenoxazone compounds (cytochrome P-450 substrates) in aqueous solution. AB - Spectral properties of the cytochrome P-450 substrates, methoxy-, ethoxy-, pentoxy-, and benzyloxyphenoxazone (MeOPx, EtOPx, PeOPx, and BzOPx, respectively) were investigated from 350 to 600 nm in ethanol and aqueous buffer. In ethanol, each alkoxyphenoxazone displayed a lambda max at 460 nm and a shoulder around 390 nm. Extinction coefficients (EmM) in ethanol were calculated as MeOPx, 20.5; EtOPx, 20.4; PeOPx, 24.7; and BzOPx, 22.4. In aqueous buffer, only MeOPx obeyed the Lambert-Beer law (lambda max = 480 nm, EmM = 22.1). Three substrates, EtOPx, PeOPx, and BzOPx, displayed anomalous behavior in aqueous solution, wherein the lambda max shifted to lower wavelengths (480-430 nm) and EmM (apparent) decreased as the alkoxyphenoxazone concentration increased. This behavior was dependent on the side chain, and the concentrations at which the spectral changes took place were estimated as: BzOPx, 2 microM; PeOPx, 5 microM; EtOPx, 17 microM; and MeOPx, greater than 20 microM. The blue shift and decreased EmM (apparent) observed for PeOPx at high concentration in aqueous buffer was reversed at high temperature. Unlike EtOPx, PeOPx, and BzOPx, and like MeOPx, hydroxyphenoxazone (resorufin) and unsubstituted phenoxazone obeyed the Lambert-Beer law in aqueous buffer and ethanol. The data suggest that the pentoxy and benzyloxy substituents facilitated a self-association process among the phenoxazones in aqueous solution. The data further show that aqueous solutions should be avoided when spectral data are used to determine alkoxyphenoxazone concentrations. PMID- 2593133 TI - Subacute inhalation of cigarette smoke by pregnant and lactating rodents: AHH changes in perinatal tissues. AB - To study the transplacental acquisition of tobacco smoke products and the effects on fetal tissue enzymes, pregnant rats, guinea pigs, and hamsters were exposed to freshly generated cigarette smoke via a nose-only inhalation system on a daily basis through the latter one-third (guinea pigs) or latter half (rats, hamsters) of the gestational period. Following euthanasia on the day of parturition, microsomal aryl hydrocarbon hydroxylase (AHH) activities were determined in the lungs, livers, and kidneys of both dams and fetuses. The possible acquisition of tobacco smoke products via the milk was studied by exposing lactating dams to cigarette smoke daily for either 4 or 14 days (rats), 4 or 7 days (guinea pigs), or 10 days (hamsters), with analysis of tissues from the euthanized pups for AHH. Pups were also exposed directly (nose only) to cigarette smoke. In the treated pregnant and lactating rat, maternal pulmonary, hepatic, and renal AHH was significantly increased but only fetal lung and the liver of 14-day-old pups showed a marked induction of AHH activity. In the pregnant and lactating guinea pig, only the pulmonary and renal AHH activities were increased following exposure, whereas in the fetuses and nursing pups, none of the tissue AHH activities was significantly altered by exposure. In the pregnant and lactating hamster, only the pulmonary AHH was increased following exposure to cigarette smoke, whereas the activity in fetal and pup tissues remained unchanged from the levels observed in control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593135 TI - Effects of chronic administration of doxorubicin on myocardial creatine phosphokinase and antioxidant defenses and levels of lipid peroxidation in tissues and plasma of rats. AB - Tissue and plasma levels of thiobarbituric acid reactive substances (TBARS) were measured in rats treated chronically with doxorubicin. In addition, heart creatine phosphokinase and antioxidant defenses were examined. Male rats received doxorubicin (DXR) 2 mg/kg or vehicle weekly subcutaneously for 13 weeks and were sacrificed at 14 and 19 weeks, 1 and 6 weeks after the last dose, respectively. Histological evaluation in DXR-treated rats at 14 and 19 weeks found significant and progressive cardiac and renal lesions as compared to controls. Heart TBARS were unchanged from controls. Plasma and kidney levels of TBARS were elevated above controls at both 14 and 19 weeks. Lung levels of TBARS were significantly elevated above controls at 14 weeks. Liver levels of TBARS were elevated at 19 weeks. Heart creatine phosphokinase activity was significantly depressed from controls at both 14 and 19 weeks. Heart glutathione peroxidase and superoxide dismutase activities were unchanged from controls. Heart glutathione, glutathione reductase, glucose-6-phosphate dehydrogenase, and catalase were elevated above controls at both 14 and 19 weeks. The lack of change in heart TBARS suggests that changes in TBARS in other organs may be secondary processes. The depression of creatine phosphokinase suggests that levels of adenosine triphosphate may be insufficient to sustain the myocardial function and this may partly be responsible for DXR-induced cardiac myopathy. PMID- 2593134 TI - Sodium arsenite induced alterations in bilirubin excretion and heme metabolism. AB - The acute administration of sodium arsenite (AsIII) to rats resulted in a biphasic alteration of the hepatic cytosolic "free" heme pool. The first stage was an increase in the cytosolic "free" heme without significant effects on the content of cytochrome P-450 or on bilirubin excretion. The second stage consisted of a continuous fall of the cytosolic "free" heme and of the content of cytochrome P-450. These changes were concurrent with an eight-fold increase in heme oxygenase activity and associated with marked elevations in the biliary excretion of bilirubin. The bile was collected from chronically cannulated rats to avoid artifacts related to anesthesia or post anesthetic effects. The rapid increase in biliary excretion of labeled heme degradation products indicated an increased breakdown of newly synthesized heme. Immunoelectrophoresis of bile proteins showed an altered pattern of bile protein excretion. The increased biliary haptoglobin suggested some hemolysis, while the reduction in the free immunoglobulin A (IgA) secretory component showed an AsIII-related decreased protein transport across hepatocytes to bile. Further research is required to assess the direct role of an increased heme degradation in the genesis of the hepatotoxic effects of AsIII. PMID- 2593136 TI - Functional characteristics of the cardiac sarcolemmal monocarboxylate transporter. AB - We have previously shown that a mechanism for transporting L-lactate is located in cardiac sarcolemmal membranes (Am. J. Physiol. 252:C483-C489, 1987). This mechanism has now been shown to transport pyruvate also. The transporter recognizes a wide range of monocarboxylic acids with chain lengths of three to six carbons, as evidenced by their ability to inhibit L-lactate uptake into sarcolemmal vesicles. The ability of the monocarboxylate analogues to inhibit depends strongly on the nature of substituents, particularly at the second carbon. L-lactate and pyruvate transport are not affected by dicarboxylates other than oxaloacetate. The transporter is inhibited by the protein modifiers diethylpyrocarbonate, dinitrofluorobenzene, and phenylisothiocyanate. Diethylpyrocarbonate inhibition is not reversed by hydroxylamine, nor is dinitrofluorobenzene inhibition reversed by thiol reagents, suggesting that the target residues are not histidine, or tyrosine or cysteine, respectively. Several monocarboxylates effectively protect the transporter from inhibition by the modifying reagents, suggesting that the modified residue(s) may be at or near the binding site. Alternatively, the target amino acid(s) in the transport protein may become inaccessible due to a conformation change triggered by the substrate analogues. Overall, the results suggest that a sensitive free amino group, associated with substrate binding, is attacked by the protein-modifying reagents. PMID- 2593137 TI - Interaction among anion, cation and glucose transport proteins in the human red cell. AB - The time course of binding of the fluorescent stilbene anion exchange inhibitor. DBDS (4.4'-dibenzamido-2.2'-stilbene disulfonate), to band 3 can be measured by the stopped-flow method. We have previously used the reaction time constant. tau DBDS, to obtain the kinetic constants for binding and, thus, to report on the conformational state of the band 3 binding site. To validate the method, we have now shown that the ID50 (0.3 +/- 0.1 microM) for H2-DIDS (4.4'-diisothiocyano 2.2'-dihydrostilbene disulfonate) inhibition of tau DBDS is virtually the same as the ID50 (0.47 +/- 0.04 microM) for H2-DIDS inhibition of red cell Cl- flux, thus relating tau DBDS directly to band 3 anion exchange. The specific glucose transport inhibitor, cytochalasin B, causes significant changes in tau DBDS, which can be reversed with intracellular, but not extracellular, D-glucose, ID50 for cytochalasin B modulation of tau DBDS is 0.1 +/- 0.2 microM in good agreement with KD = 0.06 +/- 0.005 microM for cytochalasin B binding to the glucose transport protein. These experiments suggest that the glucose transport protein is either adjacent to band 3, or linked to it through a mechanism, which can transmit conformational information. Ouabain (0.1 microM), the specific inhibitor of red cell Na+,K+-ATPase, increases red cell Cl- exchange flux in red cells by a factor of about two. This interaction indicates that the Na+,K+-ATPase, like the glucose transport protein, is either in contact with, or closely linked to, band 3. These results would be consistent with a transport protein complex, centered on band 3, and responsible for the entire transport process, not only the provision of metabolic energy, but also the actual carriage of the cations and anions themselves. PMID- 2593138 TI - Interactions between anion exchange and other membrane proteins in rabbit kidney medullary collecting duct cells. AB - In separated outer medullary collecting duct (MCD) cells, the time course of binding of the fluorescent stilbene anion exchange inhibitor, DBDS (4,4' dibenzamido-2,2'-stilbene disulfonate), to the MCD cell analog of band 3, the red blood cell (rbc) anion exchange protein, can be measured by the stopped-flow method and the reaction time constant, tau TDBDS, can be used to report on the conformational state of the band 3 analog. In order to validate the method we have now shown that the ID50D,DBDS,MCD (0.5 +/- 0.1 microM) for the H2-DIDS (4,4' diisothiocyano-2,2'-dihydrostilbene disulfonate) inhibition of tau DBDS is in agreement with the ID50,Cl-MCD (0.94 +/- 0.07 microM) for H2-DIDS inhibition of MCD cell Cl- flux, thus relating tau DBDS directly to anion exchange. The specific cardiac glycoside cation transport inhibitor, ouabain, not only modulates DBDS binding kinetics, but also increases the time constant for Cl- exchange by a factor of two, from tau Cl- = 0.30 +/- 0.02 sec to 0.56 +/- 0.06 sec (30 mM NaHCO3). The ID50,DBDS,MCD for the ouabain effect on DBDS binding kinetics is 0.003 +/- 0.001 microM, so that binding is about an order of magnitude tighter than that for inhibition of rbc K+ flux (KI,K+,rbc = 0.017 microM). These experiments indicate that the Na+,K+-ATPase, required to maintain cation gradients across the MCD cell membrane, is close enough to the band 3 analog that conformational information can be exchanged. Cytochalasin E (CE), which binds to the spectrin/actin complex in rbc and other cells. modulates DBDS binding kinetics with a physiological ID50,DBDS,MCD (0.076 +/- 0.005 microM); 2 microM CE also more than doubles the Cl- exchange time constant from 0.20 +/- 0.04 sec to 0.50 +/- 0.08 sec (30 mM NaHCO3). These experiments indicate that conformational information can also be exchanged between the MCD cell band 3 analog and the MCD cell cytoskeleton. PMID- 2593139 TI - Inactivation of the rabbit parotid Na/K/Cl cotransporter by N-ethylmaleimide. AB - The inactivation of the rabbit parotid Na/K/Cl cotransporter by the irreversible sulfhydryl reagent N-ethylmaleimide (NEM) is studied by monitoring its effect on high affinity bumetanide binding to the carrier. NEM reduces the number of bumetanide binding sites with no significant change in the affinity of those remaining. NEM also reduces KCl-dependent 22Na flux via the cotransporter by the same factor as the reduction in bumetanide binding sites. Both bumetanide and its analogue furosemide can protect against the effect of NEM. The concentration range over which this protection occurs is in good agreement with affinities of these two compounds for the high affinity bumetanide binding site (2.6 and 8.5 microM, respectively), indicating an association of this site with the site of action of NEM. Also consistent with this hypothesis are the observations that (i) sodium and potassium, both of which are required for high affinity bumetanide binding, increase the rate of inactivation of binding by NEM and (ii) chloride, at concentrations previously shown to competitively inhibit bumetanide binding, protects the cotransporter against NEM. The effects of NEM on bumetanide binding are mimicked by another highly specific sulfhydryl reagent, methyl methanethiolsulfonate. The apparent rate constant for inactivation of high affinity bumetanide binding by NEM is a hyperbolic function of NEM concentration consistent with a model in which the inactivation reaction is first order in [NEM] and proceeds through an intermediate adsorptive complex. The data indicate that the presence of a reduced sulfhydryl group at or closely related to the bumetanide binding site is essential for the operation of the parotid Na/K/Cl cotransporter. PMID- 2593142 TI - Infection control practices in Michigan dental offices: report of a survey. PMID- 2593140 TI - Activation of Cl-/OH- exchange by parachloromercuribenzoic acid in rabbit renal brush-border membranes. AB - The effect of the sulfhydryl reagent parachloromercuribenzoic acid (PCMB) on chloride transport was examined in rabbit renal brush-border membrane vesicles (BBMV). PCMB had no effect on the chloride conductive pathway. In the presence of an inside-alkaline pH gradient and a K-/valinomycin voltage clamp, the addition of PCMB stimulated 36Cl uptake and induced a threefold overshoot above the equilibrium value, indicating Cl/OH exchange. The effect of PCMB was reversed by dithiothreitol. Cl/OH exchange was not observed in the absence of PCMB. PCMB activated Cl/OH exchange persisted even when the membrane potential was made inside-negative relative to the controls, thus, demonstrating that PCMB's effect on 36Cl uptake under pH-gradient conditions is not mediated by parallel Cl- and H+ conductive pathways. PCMB-activated Cl/OH exchange was inhibited by 4,4' diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 5-nitro-2-(3 phenylpropylamino)-benzoic acid (NPPB) with IC50 values of 290 and 80 microM, respectively. These results demonstrate that modification of sulfhydryl groups by PCMB activates Cl/OH exchange in BBMV. PMID- 2593144 TI - Treatment planning for the adult patient: a teaching program for senior dental students. PMID- 2593143 TI - The dentigerous cyst: diagnosis and treatment. PMID- 2593141 TI - Calcium-dependent potassium channel in Paramecium studied under patch clamp. AB - We have studied a class of Ca2+i-dependent K channels in inside-out excised membrane patches from Paramecium under patch clamp. single channels had a conductance of 72 +/- 9.0 pS in a solution containing 100 mM K+. The channels were selective for K+ over Rb+ with the permeability ratio of 1: 0.56, and over Na+, Cs+ or NH+4 with a ratio 1: less than 0.1. The channel activity was dependent on Ca2+i, which was applied to the cytoplasmic side; the Ca2+i concentration for the half maximal activation was 2 microM. The Hill coefficient for the Ca2+i dependence of the channel activity was 2.58, indicating that more than two Ca2+i bindings are necessary for full activation. Unlike most Ca2+i dependent K channels in other organisms, the channels in Paramecium were slightly more active upon hyperpolarization than upon depolarization. The voltage dependence was fitted to a Boltzmann curve with 41.2 mV per e-fold change in channel activity. While a high Ca2+i concentration activated the channels, it also irreversibly reduced the channel activity over time. The decay of channel activity occurred faster at higher Ca2+i concentrations. Quaternary ammonium ions suppressed ion passage through the channel; more highly alkylated quaternary ammonium ions were more efficient in blocking. Ba2+i and Ca2+i were relatively ineffective in blockage. it was concluded that these Ca2+i-dependent K channels in Paramecium are different from the previously described Ca2+i-dependent K channels, and are perhaps of a novel class. PMID- 2593145 TI - A TMJ dysfunction screening index for general practitioners. PMID- 2593146 TI - Osseointegration and the dental endosseous titanium implant interface. PMID- 2593147 TI - High-resolution low-temperature scanning electron microscopy for observing intracellular structures of quick frozen biological specimens. AB - Intracellular structures of rapidly frozen biological tissues were observed in 3 D under a low-temperature scanning electron microscope using a newly developed side-entry type cryo-holder. The present low-temperature SEM is simple, easy to operate and effective for observing biological materials at high magnification. Biological tissues (the pancreas, small intestine, brown adipose tissue and Harderian gland) freshly removed from the mouse were immediately frozen in liquid propane cooled with liquid nitrogen, and their surfaces were manually fractured using a precooled razor blade in liquid nitrogen before introducing the cryo holder into the SEM. When intracellular structures were revealed after appropriate sublimation, the specimens were coated with gold using a metal evaporator fitted to the side of the microscope column at one of the specimen chamber ports. The cryo-holder was connected to a copper braid coming from a liquid nitrogen reservoir to maintain a low temperature. Using this method, intracellular structures such as the mitochondria and endoplasmic reticulum were demonstrated at high magnifications. Ribosomal granules were discerned on the rough endoplasmic reticulum of the pancreatic acinar cells. Granular substances, presumably elementary particles, were also recognized on the mitochondrial cristae of the brown adipose tissue. The method was particularly effective for studying the 3-D configuration of lipid droplets which had been difficult to preserve by chemical fixation. PMID- 2593149 TI - Infant hearing screening in Mississippi. AB - Four national professional associations through their representatives on the Joint Committee on Infant Hearing have endorsed the importance of early identification of hearing impaired children. In this article the author reports on the past seven years of the Infant Hearing Screening Program at the University of Mississippi Medical Center. He notes that efforts are currently underway to extend the IHS Program to other hospitals in Mississippi in cooperation with the Lions Club. At the present time 22 hospitals have been equipped to screen hearing in infants. PMID- 2593150 TI - Evaluation and management of disorders of the shoulder: Part I. Evaluation of the shoulder: examination in throwing athletes. AB - The shoulder has been the subject of many recent advances in orthopaedic surgery. Arthroscopic evaluation of the glenohumeral joint and subacromial bursa has enabled the physician to increase both diagnostic and management skills. In Part I of this series, the author presents an illustrated examination of the shoulder. A thorough history and comprehensive examination may lead to an accurate diagnosis and management plan, obviating the need for expensive ancillary procedures. PMID- 2593148 TI - Correction for specimen movement after acquisition of element-specific electron microprobe images. AB - Because a long time is generally required to generate X-ray maps of specific elements by electron beam methods, images are subject to a loss of resolution due to stage movement. Methods have been previously described for correcting stage drift during exposure by sensing the drift and deflecting the beam to follow the stage; but these methods require modifications of the equipment. When the drift is not excessive, it is possible to correct a series of images after the exposure series is finished. Here we demonstrate two methods for correcting the drift, one based on manual assignment of specimen position and one on the use of cross correlation functions to determine objectively the misalignment of images in the series. The success of the methods is illustrated in calcium-specific images of a bone section that show the collagen periodicity after drift correction. PMID- 2593151 TI - Our real power--a myth. PMID- 2593152 TI - Sex education in the schools. PMID- 2593153 TI - Terming procedure "experimental" not violation of antitrust. PMID- 2593154 TI - Self-injection of papaverine and phentolamine in the treatment of psychogenic impotence. AB - This study prospectively assessed the use, effectiveness, and sexual and psychosocial impact of self-injection treatment in 15 men with psychogenic impotence. Sixty percent dropped out of self-injection treatment by 6 months. Those who remained used self-injections about four times monthly with a 94% success rate. Frequency of intercourse and sexual satisfaction increased. Anxiety decreased, and trends toward improvement in depression and self-esteem were evident. Qualitative data indicated that performance anxiety was not alleviated, dependence upon injections for intercourse remained, symptom substitution did not occur, and capacity for intimacy was not improved. PMID- 2593155 TI - Prolactin and sexual dysfunction in women. AB - Serum prolactin levels were measured in 48 consecutive sexually dysfunctional women who presented to a sexuality clinic. The prevalence of hyperprolactinemia and mean prolactin level of this group were compared to a control group (blood donor volunteers) of 93 women. One woman in the study group (2.1%) was hyperprolactinemic (serum prolactin greater than 15 micrograms/L). However, the differences in both prevalence of hyperprolactinemia and mean prolactin levels, between groups, were not statistically significant. Neither were differences found in mean prolactin levels among subgroups of women in different diagnostic categories and in those with single vs. multiple diagnoses. Nonetheless, because hyperprolactinemia is readily treatable, we would recommend prolactin determinations in sexually dysfunctional women, particularly in those with associated reproductive irregularity or in whom organic etiology is clinically suspect. PMID- 2593156 TI - Gender differences in sexual behaviors and fantasies in a college population. AB - This study presents male and female responses of 193 university students to questions about sexual experiences and fantasies. There are few significant gender differences in experiences, but many in fantasies. Males fantasized about sex more and exhibited greater interest in partner variation and in the spectrum from domination to sadism. While male sexuality is often described as aggressive/sadistic and female sexuality as passive/masochistic, most men and women in our population do not report fantasies supporting such stereotypes. PMID- 2593157 TI - Topics of interest in premarital counseling: clients' views. PMID- 2593158 TI - Changes in the premarital and marital sexual life of Czechoslovak women born between 1911 and 1970. AB - Using the interview method, three sexologists examined, over a period of 36 years, the sexual development and life of 2,425 gynecological patients who were sent to Franzensbad for after-treatment of conditions following gynecological inflammations or surgery. They had all been married at least 1 year and when interviewed were 20-40 years old. The average age at the time of the first coitus dropped from 20.75 among the women born in the decade 1911-1920 to 17.8 among those born between 1961 and 1970. As far as premarital sexual life is concerned, the number of young women with numerous coital partners before marriage has continuously increased since 1931. About 50% of young brides today had premarital sexual contacts with 1-3 partners. Over the decades between 1921 and 1970, the number of women with 4-10 premarital coital partners has increased from 1% to 12%. Among women born in the decade 1961-1970, there has been a distinct increase in those who achieve coital orgasm only rarely to 26%. This is the highest percentage of this type of insufficient sexual reactivity since 1911. This unfavorable change in sexual life of young married women is discussed in the context of negative social environmental factors in Czechoslovakia today. The study concludes with the opinion that frequency of coital orgasm in women is a sensitive indicator of social environmental influences in a given society. PMID- 2593159 TI - Comprehensive sexual health centers: is it time? AB - Psychiatric epidemiologic research, mental health professionals, and nonpsychiatric physicians still largely avoid dealing with the problems of sexual identity and function. The Department of Psychiatry at Case Western Reserve University, in contrast to these trends, has established a Center for Human Sexuality, an innovative mental health center that employs full- and part-time staff to provide services, education, and research. The Center may serve as a model for other institutions that perceive the social, academic, and economic value of dealing with these high prevalence, underserved problems. The support of administration and the multidisciplinary interaction of mental health professionals among themselves and with nonpsychiatric physicians have been crucial to the Center's viability. Strategies for dealing with health care administration are discussed. PMID- 2593160 TI - Estimating the long-term probability of developing breast cancer. PMID- 2593161 TI - Immunotoxin therapy: prospects for the future. PMID- 2593162 TI - Serum cholesterol and cancer: is there a connection? PMID- 2593163 TI - Industry asked to help develop better diagnostic techniques. PMID- 2593164 TI - Funding for cancer centers: a challenge of scarce resource allocation. PMID- 2593165 TI - Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. AB - To assist in medical counseling, we present a method to estimate the chance that a woman with given age and risk factors will develop breast cancer over a specified interval. The risk factors used were age at menarche, age at first live birth, number of previous biopsies, and number of first-degree relatives with breast cancer. A model of relative risks for various combinations of these factors was developed from case-control data from the Breast Cancer Detection Demonstration Project (BCDDP). The model allowed for the fact that relative risks associated with previous breast biopsies were smaller for women aged 50 or more than for younger women. Thus, the proportional hazards models for those under age 50 and for those of age 50 or more. The baseline age-specific hazard rate, which is the rate for a patient without identified risk factors, is computed as the product of the observed age-specific composite hazard rate times the quantity 1 minus the attributable risk. We calculated individualized breast cancer probabilities from information on relative risks and the baseline hazard rate. These calculations take competing risks and the interval of risk into account. Our data were derived from women who participated in the BCDDP and who tended to return for periodic examinations. For this reason, the risk projections given are probably most reliable for counseling women who plan to be examined about once a year. PMID- 2593166 TI - Model predicting survival in stage I melanoma based on tumor progression. AB - We used the lesional steps in tumor progression and multivariable logistic regression to develop a prognostic model for primary, clinical stage I cutaneous melanoma. This model is 89% accurate in predicting survival. Using histologic criteria, we assigned melanomas to tumor progression steps by ascertaining their particular growth phase. These phases were the in situ and invasive radial growth phase and the vertical growth phase (the focal formation of a dermal tumor nodule or dermal tumor plaque within the radial growth phase or such dermal growth without an evident radial growth phase). After a minimum follow-up of 100.6 months and a median follow-up of 150.2 months, 122 invasive radial-growth-phase tumors were found to be without metastases. Eight-year survival among the 264 patients whose tumors had entered the vertical growth phase was 71.2%. Survival prediction in these patients was enhanced by the use of a multivariable logistic regression model. Twenty-three attributes were tested for entry into this model. Six had independently predictive prognostic information: (a) mitotic rate per square millimeter, (b) tumor-infiltrating lymphocytes, (c) tumor thickness, (d) anatomic site of primary melanoma, (e) sex of the patient, and (f) histologic regression. When mitotic rate per square millimeter, tumor-infiltrating lymphocytes, primary site, sex, and histologic regression are added to a logistic regression model containing tumor thickness alone, they are independent predictors of 8-year survival (P less than .0005). PMID- 2593167 TI - Synergistic antitumor activity of etoposide and human interleukin-1 alpha against human melanoma cells. AB - To investigate the possibility of increased activity of cytotoxic anticancer drugs combined with cytokines, we treated human melanoma cells with combinations of etoposide (VP-16) and human recombinant interleukin-1 alpha (rIL-1 alpha). We evaluated the combined cytotoxic effects of VP-16 and rIL-1 alpha using A375-C6 cells, which are sensitive to rIL-1 alpha, and A375-C5 cells, a clonal variant line resistant to rIL-1 alpha. We used the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium-bromid e) assay and the inhibition of [3H]thymidine incorporation into DNA. We analyzed data using the median effects principle of Chou and Talalay (Chou's analysis). The calculated combination index values, at a dose ratio of VP-16 to rIL-1 alpha of 12:1 in simultaneous exposure, indicated synergistic cytotoxicity toward both A375-C6 cells and A375-C5 cells. We observed more pronounced synergism with VP-16 and rIL-1 alpha toward the A375-C5 IL-1 alpha-resistant melanoma cells. These results suggest that rIL-1 alpha combined with cytotoxic antitumor drugs may provide increased benefit in the treatment of malignant melanoma. PMID- 2593168 TI - Quantitative carcinogenesis in man: solar ultraviolet B dose dependence of skin cancer in Maryland watermen. AB - Skin cancer is the most common form of cancer in humans and occurs primarily on sun-exposed areas of the body. In a study of 808 Caucasian Maryland watermen, we examined the prevalence of nonmelanoma skin cancer in relation to age and exposure to solar ultraviolet B (UVB) radiation. For each study subject, the exposure to solar UVB radiation for each year of life after the age of 16 years was calculated. We obtained the data for this analysis by combining a detailed occupational history with laboratory and field measurements. Prevalence of the three major types of nonmelanoma skin neoplasms was analyzed: squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and actinic keratosis (AK). Average annual exposure to UVB radiation was strongly correlated with the prevalence of SCC, but not with the prevalence of BCC or AK. This finding is consistent with dose saturation (plateau in dose-response relationship) for the induction of BCC and AK in humans with high annual exposure to UVB radiation. In addition, two small groups of apparently hypersusceptible individuals were present in the population. One group had SCC despite low annual exposure to UVB radiation, and the other group had multiple skin cancers despite average exposure to UVB radiation. PMID- 2593169 TI - Detection of the tumor-associated glycoprotein antigen (TAG-72) in premalignant lesions of the colon. AB - We used monoclonal antibody B72.3 to study the expression of the colorectal carcinoma-associated antigen TAG-72 in premalignant colonic lesions with the immunoperoxidase technique. This antigen, which is rarely detectable in the normal colonic epithelium, was expressed in 13 of 19 adenomas with moderate to severe dysplasia and nine of nine cases of inflammatory bowel disease. The antibody reacted with the normal-appearing mucosa adjacent to a carcinoma in 10 of 12 cases, although only eight of the tumors expressed the antigen. The expression of the TAG-72 antigen in the colonic epithelium may be an early marker of malignant transformation. PMID- 2593170 TI - Cancer incidence and cancer mortality in relation to serum cholesterol. AB - We studied cancer incidence and mortality from cancer and coronary heart disease in relation to serum cholesterol levels in 92,710 individuals followed-up in the nationwide Swedish Cancer Register and the Swedish Cause of Death Register for 18 20 years. According to Cox's proportional hazard model, total cancer incidence and total cancer mortality were negatively correlated to serum cholesterol level (P less than .001). The negative correlations were most pronounced during the first years of follow-up. Cancer mortality data showed a stronger negative association to cholesterol than did incidence data during the first 10 years of follow-up (P less than .05). Mortality from coronary heart disease was positively correlated to serum cholesterol (P less than .001) during the entire follow-up. In contrast to most studies that were based on mortality data, our results of the comparison of incidence and mortality data of the same cohort are in agreement with those of a cholesterol-lowering effect of a preclinical cancer. Efforts by investigators and clinicians to lower serum cholesterol to prevent cardiovascular disease are, according to the present findings, not likely to increase cancer mortality risks but would extend life, irrespective of cause of death. PMID- 2593171 TI - Pharmacodynamics of 5-iodo-2'-deoxyuridine in VX2 tumor-bearing rabbits. PMID- 2593172 TI - Comparison of the pharmacokinetics of octreotide injected at two subcutaneous sites. PMID- 2593173 TI - Effect of ethanol on the metabolism of trichloroethylene. AB - Trichloroethylene (TCE) is metabolized to chloral hydrate (CH) by the cytochrome P-450 monooxygenase system. CH can either be oxidized by chloral hydrate dehydrogenase to trichloroacetic acid (TCA) or reduced by alcohol dehydrogenase to trichloroethanol (TCEtOH). The oxidation reaction requires NAD+, while the reduction reaction requires NADH. Since ethanol (EtOH) is known to alter the NAD+/NADH ratio in the hepatocyte, it was coadministered with TCE in an attempt to alter the metabolism of TCE. This would provide a means for predicting interactions of ethanol on the hepatotoxicity and carcinogenicity of TCE. Male Sprague-Dawley rats were administered oral doses of either 1.52, 4.56, or 22.8 mmol/kg TCE, with the treatment group receiving an additional 1.52, 4.56, or 22.8 mmol/kg EtOH, respectively. Blood and urine samples were collected over 72 h. The clearance of TCE appeared to be saturated at the 4.56 mmol/kg dose, as evidenced by prolonged residence times for TCE in the body. Consistent with this result, there was an attenuation of the increases in the levels of TCEtOH and TCA in blood. However, the time to peak concentration of these metabolites was delayed with increasing doses and their residence time in the body was prolonged. Therefore, the area under the curve (AUC) for TCEtOH and TCA continued to increase with the higher doses of TCE. Measurement of the net output of these metabolites in urine confirmed that, although metabolism was saturated, the net metabolic conversion of TCE increased. As predicted, EtOH decreased blood levels of TCA, but only at early times at the high dose. EtOH did increase the urinary TCEtOH/TCA ratio at all dose levels. These results are consistent with the hypothesis of a more reduced state in the hepatocyte caused by the generation of excessive reducing equivalents by EtOH metabolism. The metabolism of TCE is shifted toward reduction to TCEtOH, away from oxidation to TCA. However, the effect was prominent only at extremely high doses of TCE and EtOH. PMID- 2593174 TI - Epidemiologic study of insecticide exposures, obesity, and risk of bladder cancer in household dogs. AB - A case-control study of household dogs was conducted to determine if exposure to sidestream cigarette smoke and chemicals in the home, use of topical insecticides, and obesity are associated with the occurrence of bladder cancer. Information was obtained by interview from owners of 59 dogs with transitional cell carcinoma of the bladder and 71 age- and breed size-matched control dogs with other chronic diseases or neoplasms. Bladder cancer risk was unrelated to sidestream cigarette smoke and household chemical exposures. Risk was significantly increased by topical insecticide use (OR = 1.6 for 1-2 applications per year and OR = 3.5 for greater than 2 applications per year; chi 2 trend; p = .008). This risk was enhanced in overweight or obese dogs. Further studies of this canine model may facilitate identification of specific carcinogens present in insecticides commonly used on pet animals and in the environment. PMID- 2593175 TI - Comparison of different computerized classification methods for predicting carcinogenicity from short-term test results. AB - A major obstacle to the use of short-term test results for predicting carcinogenicity is the nonavailability of methods that generate unequivocal estimations of potential carcinogenicity, even in the case of contrasting test results. We compared different mathematical classification methods such as linear discriminant analysis, the K-nearest neighbor rule (KNN), and a new ad hoc classification method called dynamic carcinogenicity assessment (DYCA). The DYCA was developed by us to explicitly reflect the biological results. Through an analysis of a real data base we pointed out the advantages and limitations of these methods. KNN was clearly inferior to the other two algorithms. The novel DYCA approach was more sensitive to carcinogens, whereas linear discriminant analysis proved better for the identification of noncarcinogens. PMID- 2593177 TI - Modulating effect of body temperature on the toxic response produced by the pesticide chlordimeform in rats. AB - Previous studies from this laboratory have demonstrated significant deficits in cardiovascular function in rats exposed to the pesticide chlordimeform (CDM) when body core temperature (TCO) was maintained at 37 degrees C. To investigate the role of TCO on CDM toxicity, similar experiments were conducted over a range of TCO values. Adult rats (n = 30) were anesthetized with sodium pentobarbital (35 mg/kg) and randomly assigned to one of six equal groups. Groups were paired and TCO was maintained in the rats in each of the respective group pairs at one of three levels (37, 35, or 33 degrees C). Rats in one group at each temperature level (groups T37, T35, and T33) were injected intraperitoneally with 60 mg/kg of CDM. Animals in the corresponding temperature-matched groups (groups C37, C35, and C33, respectively) received volume-matched injections of normal saline vehicle and served as time-paired controls. The electrocardiogram and heart rate (HR) were monitored throughout the experimental procedure. There was a significant decrease in HR in all CDM-treated groups when compared to the control group animals. The magnitude of the observed cardiac effect was attenuated in the T35 group when compared to that of the other treated groups. Similarly, lethality rates (number of deaths/total) for the T37, T35, and T33 groups were 2/5, 0/5, and 3/5, respectively; there were no deaths among the control-group animals. From these and previous data from this laboratory, we conclude there may be a beneficial effect of moderate hypothermia in rats exposed to toxic agents while more severe hypothermia appears to offer no advantage and may actually exacerbate the toxic effect. PMID- 2593176 TI - Effect of beta-naphthoflavone on o-tolyl saligenin phosphate-induced delayed neuropathy in two lines of chickens. AB - The effect of the microsomal enzyme inducer beta-naphthoflavone (beta NF) on the development of organophosphorus-induced delayed neuropathy (OPIDN) was examined in two laboratories (VPI and MSU), utilizing two strains of White Leghorn hens. A single intraperitoneal injection of beta NF at 80 mg/kg body weight 48 h prior to administration of o-tolyl saligenin phosphate (TSP), the neuroactive metabolite of tri-o-tolyl phosphate (TOTP), caused a significant increase in hepatic microsomal cytochrome P-450 concentrations and aniline hydroxylase activities after 72 h in both strains. Hepatic carboxylesterase and cholinesterase activities were not affected by beta NF treatment in either strain. Administration of TSP in single subcutaneous doses of 20 and 25 mg/kg body weight (VPI) or 30 and 60 mg/kg body weight (MSU) caused significant inhibition of whole brain neuropathy target esterase (NTE) activity 24 h postdosing, and hens subsequently developed clinical signs characteristics of OPIDN. beta NF had no significant effect on NTE inhibition or on initiation or severity of OPIDN clinical signs. However, OPIDN clinical signs were less severe in the strain of bird (MSU) with the higher intrinsic hepatic carboxylesterase activity and the higher beta NF-induced cytochrome P-450 concentration. The study indicates that microsomal enzyme induction, which has been shown to alleviate TOTP-induced delayed neuropathy, could not alleviate OPIDN resulting from exposure to TSP. This study also suggests that strain may affect susceptibility to TSP-induced delayed neuropathy. PMID- 2593178 TI - Effect of chelating agent structure on the mobilization of cadmium from intracellular deposits. AB - An examination of the efficacy of several structural types of chelating agents in the removal of cadmium from its intracellular deposits in mouse liver and kidneys reveals that of the structural types examined, only dithiocarbamates and a vicinal dithiol were able to mobilize cadmium from such intracellular sites. Esters of L-cysteine, a macrocyclic thioether, and a disulfide of a dithiocarbamate were unable to cause any appreciable decrease in either renal or hepatic cadmium levels. Charged groups such as carboxylic acid groups reduce the efficacy as well as the toxicity of the structural types that can otherwise mobilize such cadmium. It was also found that the administration of a cadmium binding polymer ip leads to only a very slight net excretion of cadmium, while the po administration of this polymer leads to no net additional cadmium excretion. Of the compounds newly reported here, some are approximately equal in cadmium-mobilizing efficacy to the most effective of previously reported compounds. PMID- 2593179 TI - Denervation and hyperinnervation in the nervous system of diabetic animals. I. The autonomic neuronal dystrophy of the gut. AB - Peripheral neuropathy is a correlate of experimental diabetes induced in rats by means of a single injection of alloxan. The autonomic and enteric innervation of the gut are profoundly affected in the small intestine of such animals. A complex process of denervation and hyperinnervation of the gut wall of diabetic animals is observed. It was previously reported that the cholinergic parasympathetic innervation of the intestine is markedly reduced. We have found that noradrenergic sympathetic axons hyperinnervate the duodenum of diabetic rats, whereas noradrenaline levels are significantly reduced in the jejunum. The putative enteric neurotransmitter dopamine is also present in higher levels in the duodenum. The intrinsic peptidergic neurons of the gut are deeply affected as well in diabetic rats. Substance P and met-enkephalin content are remarkably reduced throughout the small intestine, whereas vasoactive intestinal polypeptide levels (VIP) are significantly increased in the duodenum. Indeed, immunocytochemical staining of the ileum did reveal hypertrophy of VIP-positive axons in diabetic rats. The intrinsic serotoninergic innervation of the gut is apparently unaffected. Our results indicate that the changes of gut innervation observed in experimental diabetes are consistent with increased content and also likely with hyperinnervation by the neuronal systems involved in smooth muscle relaxation and decreased content and with denervation by those systems with smooth muscle contraction properties. Such a perturbed gut innervation may be responsible of the gastrointestinal dysfunctions that are among the most common complications of diabetes. PMID- 2593180 TI - Cholinergic agonists selectively induce proliferative responses in the mature subpopulation of murine thymocytes. AB - The incubation of murine thymocytes for 24 hr in the presence of cholinergic agonists induces selective proliferation of PNA- cells as measured by thymidine incorporation. The response of PNA- cells is mediated by the activation of nicotinic receptors. This conclusion is suggested by the inability of the muscarinic agonist, oxotremorine, to induce cell proliferation and by the inhibition exerted by the nicotinic antagonist, d-tubocurarine. The presence of cholinergic axons in the murine thymus adds biological interest to the selective expression of functional cholinergic receptors on mature thymocytes. PMID- 2593181 TI - Uptake and release of glycine in cerebellar granule cells and astrocytes in primary culture: potassium-stimulated release from granule cells is calcium dependent. AB - The properties of [3H]glycine uptake and release were studied with cerebellar granule cells, 7-9 days in vitro, (DIV) and astrocytes, 14-15 DIV, in primary cultures. The uptake of glycine in both cell types consisted of a saturable high affinity transport and nonsaturable diffusion. The transport constant (Km) and maximal velocity (V) were significantly higher in granule cells than in astrocytes. Uptake was strictly Na+-dependent and also markedly diminished in low Cl medium. The specificity of the uptake was similar in both cell types. The spontaneous release of glycine from granule cells and astrocytes was fast. Homoexchange with extracellularly added glycine in granule cells suggests that the efflux is at least partly mediated via membrane transport sites in these cells. Kainate stimulated the release more effectively in neurons than in glial cells, the effect apparently being mediated by specific kainate-sensitive receptors in both cell types. The release was enhanced by veratridine and by depolarization of cell membranes by high K (50 mM) in both neurons and astrocytes. The potassium-stimulated release was partially Ca-dependent in neurons but Ca-independent in glial cells. The results suggest a functional role for glycine in both cerebellar astrocytes and glutamatergic granule cells. PMID- 2593182 TI - Intracerebral transplantation of dissociated central nervous system tissue suspensions: use of phaseolus vulgaris leucoagglutinin as a cell marker. AB - Successfully transplanted neurons and their sprouting processes were demonstrated by Phaseolus vulgaris leucoagglutinin (PHA) marking. PHA is transported anterogradely and readily reveals the post-transplantation growth of the neuronal processes. Suspensions of fetal central nervous tissue, prepared by dissociation of embryonic rat brain, were marked with PHA and then transplanted into the striatum of nonimmunosuppressed young adult rats. At various intervals thereafter (1 day, 2 days, 1 week, 2 weeks, 1 month, and 2 months), the animals were sacrificed for histological examination with PHA and tyrosine hydroxylase (TH) immunohistochemistry. Up to 2 weeks after transplantation, PHA immunohistochemistry was capable of demonstrating grafted neurons and their presumably regenerated neuronal processes. However, at periods 1 month or longer after transplantation, PHA immunohistochemistry was unreliable. Thus, the PHA marking method has limitations in terms of its retention period, when applied to the intracerebral transplantation of dissociated cell suspensions. Nevertheless, the method presented here can be utilized to study neuronal regeneration as well as the relationship between transplanted neurons and the host tissue. PMID- 2593184 TI - Free radicals mediate peroxidative damage in guinea pig hippocampus in vitro. AB - Previous studies have shown that peroxide caused electrophysiological damage. The present study investigates the action of agents that interfere with a free radical process in an effort to define the mechanism of peroxide damage. Deferoxamine chelates iron, making it unavailable for the Fenton reaction and thereby preventing the formation of hydroxyl free radicals from peroxide. Dimethylsulfoxide (DMSO) scavenges hydroxyl free radicals. Trolox-C, a water soluble Vitamin E analog, is an antioxidant that can scavenge peroxy radicals. Slices of hippocampus were removed from brains of euthanized guinea pigs. Electrical stimulation of an orthodromic pathway to CA1 region evoked a synaptic response and a population spike. Input-output curves were generated to evaluate the protection by deferoxamine, Trolox-C, and DMSO on the synaptic damage and impaired spike generation caused by peroxide. Lipid peroxidation was measured by the thiobarbituric acid test. Peroxide was found to increase lipid peroxidation. Deferoxamine and Trolox-C protected against the peroxide-induced synaptic damage, impaired spike generation, and lipid peroxidation. DMSO was ineffective synaptically but reduced peroxide damage to spike generating mechanisms and further lipid peroxidation. The data support the hypothesis that peroxide causes damage through a free radical mechanism. PMID- 2593183 TI - Increased density of perivascular adrenergic innervation in tibial and vagus nerves of spontaneously hypertensive rats. AB - Adrenergic innervation of epiperineurial arterioles and of the endoneurium of the tibial and vagus nerves of spontaneously hypertensive rats (SHR) and normotensive controls (WKY) was studied by glyoxylic acid-induced fluorescence and paraformaldehyde-induced fluorescence methods. Adrenergic perivascular innervation of epiperineurial arterioles in both nerves was denser in SHR than in controls. Mean density in the endoneurium also was higher in SHR in both nerve types. These results suggest that adrenergic perivascular innervation, which may influence nerve blood flow, becomes greater in density in peripheral nerves during chronic hypertension. PMID- 2593185 TI - Practical evaluation of trauma deaths. AB - The TRISS method of auditing trauma deaths necessitates audit of patients with minor injuries who die of their underlying medical problems. Using an anatomic definition of injury as a criterion for audit, as suggested by Wesson et al. at the Hospital for Sick Children in Toronto, excludes patients with minor injuries but necessitates audit of patients who expired due to systems problems rather than in-hospital patient care. We propose combining the TRISS and Toronto methods in order to identify the deaths truly appropriate for detailed review of hospital care. Fifty-four trauma deaths over a 22-month period were audited and categorized as frankly preventable, potentially salvageable, or nonpreventable. Considering only in-hospital care, the deaths designated as potentially salvageable by audit were likely to be identified by both TRISS and Toronto, while deaths targeted by only one system were more likely to be nonpreventable by audit. The predictive value of this combination of methods (84.6%) was better than Toronto (52.4%) or TRISS (54.5%) using audit results as the standard for comparison. This simple computerized method may serve as a practical and inexpensive method of targeting deaths for in-depth review. PMID- 2593186 TI - Impact of pre-trauma center care on length of stay and hospital charges. AB - The purpose of this paper is to identify factors associated with improved utilization of health care resources in the treatment of patients with injury. A prospective cohort study was conducted of all trauma patients admitted to a trauma center from April 15, 1987 to February 28, 1988. Altogether, 877 patients were entered into the study: 673 (76.7%) scene patients, and 204 (23.3%) interhospital transfers. The mean length of stay (LOS) for scene patients was 12 days, with mean charges of $8,781, whereas the mean LOS of interhospital transfers was 18 days, with mean charges of $16,734. When controlled for confounding variables, the scene patients had significantly shorter LOS and charges than matched interhospital transfers. This difference was more pronounced for the air-transported patients than for ground-transported patients. The elderly utilize more resources than young patients when matched for severity of injury. It is beneficial to the patients and the health care system to have severely injured trauma patients transported directly to a trauma center from the scene of an injury. Helicopter emergency medical services can enhance the ability of a trauma care system to decrease health care costs. PMID- 2593187 TI - IQ levels following trauma. AB - One hundred fifteen consecutive trauma patients who experienced a head injury and were administered a Wechsler Intelligence Scale as outpatients were selected for study from the Neuropsychology Registry. These patients ranged in age from 4 to 61 years. At the time of examination, all were living at home with their families. Dividing this group of patients on the basis of a Glasgow Coma Score (GCS) of 10 revealed significant differences in group mean post-traumatic IQs. The more severely injured group of patients had a mean post-traumatic IQ of 93.6; the less severely injured patients had a mean IQ of 103.5. The difference between these two groups is significant (p less than 0.005). When divided on the basis of a GCS of 13, the more severely injured group of patients had a mean post traumatic IQ of 94.2 and the less severely injured group of patients had a mean post-traumatic IQ of 104.2. The difference between these two groups is also statistically significant (p less than 0.0005). There was no statistically significant (p greater than 0.05) difference in the mean post-traumatic IQs of these patients divided on the basis of an Injury Severity Score (ISS) of 15. However, there was a significant difference (p less than 0.05) when the patients were divided at ISS of 17. The less severely injured patients had a mean post traumatic IQ of 101.2 and the more severely injured patients had a mean post traumatic IQ of 95.8. The difference between these two groups is statistically significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593188 TI - Penetrating renovascular trauma. AB - A 10-year experience with 39 patients having 40 renovascular injuries is presented. The overall mortality rate was 30%, predominantly from extensive associated trauma. Nephrectomy was performed in 20 patients (51%). Only 50% of the patients had attempted repair or ligation of the renal vessels. Renal salvage was possible in 23% of the total group and included 33% of these for isolated renal artery injuries and 43.6% for renal vein injuries. Our experience and a review of the literature suggest that nephrectomy still is the most expeditious method of management of renal vascular injuries. The extent of the associated trauma determines the fate of the involved kidney after renovascular trauma. Renal artery repair rarely is possible and seldom is successful. Renal vein injuries carry a better prognosis. PMID- 2593189 TI - Blunt tibial artery trauma: predicting the irretrievable extremity. AB - Patients suffering blunt leg trauma resulting in below-knee fracture, tibial artery injury, and soft-tissue damage are at major risk for amputation. In an attempt to identify the factors which may forecast limb loss despite vascular surgical repair, all patients with tibial fractures admitted between 1980-1988 were reviewed. Forty-four of 366 (12%) patients presented with clinical evidence of tibial artery injury. Twenty-seven of these 44 patients had angiographic evidence of at least one patent tibial vessel providing adequate distal flow. The remaining 17 patients required operative repair of injured tibial arteries because of persistent distal ischemia. The amputation rate was 35% (6/17--4 BKA, 2 AKA), three of these having patent vascular repairs at the time of the amputation. Operative indications for amputation were ischemic nonviable muscle in three patients, and severe soft-tissue wound infection in three. Patients who required amputation had a significantly greater incidence (Fisher's exact test) of three or more fascial compartments involved in muscular injury (p = 0.005), two or more injured tibial vessels (p = 0.01), failed vascular reconstruction (p = 0.03), a cadaveric foot at initial exam (p = 0.03), and severe muscle crush injury or muscle tissue loss (p = 0.03). No extremity was salvaged when more than two of these factors was present, and a failed vascular reconstruction led to limb amputation in all cases. These factors will predict an irretrievable extremity following blunt tibial artery trauma, allowing amputation before life threatening wound sepsis develops. PMID- 2593190 TI - Evaluation of blunt abdominal trauma occurring during pregnancy. AB - Evaluation of abdominal trauma in pregnant patients presents a number of dilemmas. Few series compare the various modalities available in this situation. The present review characterizes various techniques and their results. The charts of all patients with a secondary diagnosis of pregnancy admitted to a Level I trauma center over a 7 1/2-year period were reviewed. Forty were considered to have sustained possible blunt abdominal trauma: 30 were occupants in motor vehicle collisions, five were pedestrians, four sustained falls, and one was riding a motorcycle. Immediate laparotomy for emergency caesarean section or other indications was performed in three cases (7%). In 13 cases (32%) evaluation was accomplished by diagnostic peritoneal lavage (DPL). Three patients (7%) underwent computerized tomography of the abdomen. The remaining 22 patients (55%) were observed with serial physical exams, and hematocrits. The group that was observed had a mean ISS of 5.9. The mean Glasgow Coma Score (GCS) was 14.9. No patients had to undergo exploratory laparotomy for abdominal injury during hospitalization. In the 13 patients undergoing DPL, the mean ISS was 34.6, and the mean GCS was 10.6. Overall accuracy was 92% with no major complications. Pregnant patients sustaining minor injuries and blunt abdominal trauma may be safely observed. Those with major injuries, shock, altered mental status, or neurologic deficit require further studies to rule out intra-abdominal injury. Diagnostic peritoneal lavage proved to be safe and accurate in these patients. Diagnostic peritoneal lavage proved to be safe and accurate in these patients. CT scan and ultrasonography are other modalities which merit further assessment as a primary diagnostic technique in abdominal trauma occurring during pregnancy. PMID- 2593191 TI - Measured energy expenditure in severe head trauma. AB - Metabolic profiles of 20 patients admitted to the Conemaugh Valley Memorial Hospital Trauma Unit from July 1987 through June 1988 with Glasgow Coma Scale Scores of 7 or less were retrospectively reviewed. Analysis of Injury Severity Scale (ISS) determinations indicated that all patients had major closed head injury, and associated injuries were minor in nature. No significant co-morbid disease states were present in this patient population. All patients required mechanical ventilatory support, and within 48 hours of admission measurements of oxygen consumption (VO2), carbon dioxide production (VCO2) and respiratory quotient (VCO2/VO2) were made using a Beckman Metabolic Measurement Cart which employs indirect closed calorimetry to assess resting energy expenditure (REE). When predicted values of REE and VO2 (derived from the Harris-Benedict equation) were compared to actual measured data, the percentage increase over predicted was 160 +/- 37 (p less than 0.005) and 166 +/- 43 (p less than 0.005), respectively. Based on these observations it is evident that patients with severe head trauma are physiologically in an early hypermetabolic state, and that values of REE derived from standard formula are grossly inaccurate, leading to inadequate nutritional support. PMID- 2593192 TI - Comparison of blood gases during transport using two methods of ventilatory support. AB - Transportation of critically ill patients requiring ventilatory support represents a common, yet difficult, problem faced by clinicians. We examined 28 patients requiring transport in a prospective, randomized fashion, comparing manual ventilation with ventilation provided by a transport ventilator. Patients were ventilated to their destination with one method and returned with the alternate method. After manual ventilation, all patients showed a marked respiratory alkalosis (pH increased from 7.39 to 7.51 and PaCO2 decreased from 39 to 30 torr). After ventilation with the transport ventilator, no appreciable changes in pH or PaCO2 were seen. Oxygenation remained stable with both methods. No patient suffered hemodynamic instability, although two patients in the manual ventilation group developed cardiac arrhythmias. We conclude that when ventilatory support is required during transport, a transport ventilator produces reliable control of ventilation. PMID- 2593194 TI - Delayed identification of skeletal injury in multisystem trauma: the 'missed' fracture. AB - Delay in diagnosis of musculoskeletal injury in multiply injured patients may potentially lead to functional or cosmetic disability in survivors. In an 18 month prospective study to determine the incidence and spectrum of delayed recognition of skeletal injury at our Level I trauma center, delayed diagnosis of 39 fractures was made in 26 of 1,006 consecutive blunt trauma patients. The delay in recognition ranged from 1-91 days. Twenty-one (55%) of the fractures were not X-rayed at the time of admission, but nine (23%) fractures were clearly visible on admission films. Four (10%) fractures were missed because of technically inadequate X-rays, and five (13%) had adequate X-rays but could not be identified on admission films. In only two instances was a second anesthetic exposure required for operative therapy. For the patients in this series, the delay of fracture identification was not felt to contribute to additional long-term cosmetic, functional, or neurologic problems. Continued clinical and radiologic surveillance is required in multiply injured patients to prevent musculoskeletal diagnostic failure. PMID- 2593193 TI - Indications for barium enema preceding colostomy closure in trauma patients. AB - The need for a barium enema (BE) preceding colostomy closure is controversial. In the process of evaluating the usefulness of BE before closure of colostomies performed for colorectal injuries, we reviewed our experience with 84 trauma patients who underwent BE before colostomy closure. Patients who had their colonic injuries repaired or diverted during the initial procedure did not benefit from the precolostomy closure contrast study. In this group of patients artifacts on BE had to be ruled out by endoscopy or repeat radiography in 9.5% of patients. Barium enema was found beneficial in evaluating colorectal injuries below the peritoneal reflection in one out of 20 patients. However, since the rectal injuries are not usually explored and repaired during the initial procedure, investigation by endoscopy and contrast studies may still be indicated preceding colostomy closure. PMID- 2593195 TI - Toxicology screening in urban trauma patients: drug prevalence and its relationship to trauma severity and management. AB - Although toxicology screening is often used when treating trauma patients, its utility and significance remain controversial. Data from 623 toxicology screens performed in urban trauma center patients with mental status alterations are reported. The study patients were predominantly black and male, with a mean age of 32 (+/- 22) years. Overall, 86% of screens were positive. Substances of abuse, including ethanol, were noted in 525 (84%) of urine toxicology screens. Ethanol, cannabinoids, and cocaine were the drugs most commonly found in urine, with positivity noted in 53%, 37%, and 34% of screens. Serum analysis was 44% positive, with ethanol noted in 41% of patients. In blacks, the odds ratio of illicit drug use before trauma ranged from 1.9 to 4.2 (p less than 0.005), and in those aged 17 to 40 years, the odds ratio for illicit urine drugs ranged from 4.7 to 16.8 (p less than 0.001). In patients older than 40 years, the odds of a positive serum ethanol level were 1.7 times greater than in younger patients, and a level above 300 mg% was 3.8 times more likely in this age group (p less than 0.001). When serum ethanol was detected, the odds ratio of a head injury was 1.4 relative to patients without serum ethanol (p less than 0.06), and the odds ratio for abdominal injury was 1.6 for patients with serum ethanol (p less than 0.03). The odds of a TS less than 12 were 1.8 (p less than 0.05), and the odds of a GCS less than 12 were 3.3 (p less than 0.001) with ethanol levels greater than 100 mg%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593196 TI - Patterns of alcohol and drug abuse in an urban trauma center: the increasing role of cocaine abuse. AB - Alcohol continues to play a major etiologic role in blunt trauma. It is involved in 65-70% of fatal highway crashes. The role of illicit drugs, although accepted as an etiologic factor in trauma, is less well described. This is especially true of blunt and penetrating trauma related to violent crime. During a 9-month period, in a randomly selected group, blood and urine samples were taken from 169 traumatized patients for alcohol and general toxicology screens. There were 81 cases (47.9%) related to violent crime. One hundred twenty-six patients (74.5%) tested positive for illicit or prescription drugs in their blood. These included cocaine (54.4%), cannabinoids (37.2%), barbiturates (7.1%), amphetamines (4.7%), benzodiazepines (10.1%), opiates (9%), and codeine (1%). Sixty-one patients (35.5%) tested positive for alcohol. Alcohol was found in 6.2% of violent crime related cases. Illicit drugs were found in 80.3% of violent crime-related cases. Alcohol and drugs, especially illicit drugs, are major etiologic factors in both accidental and crime-related trauma in the urban population. All patients admitted to trauma centers, especially urban trauma centers, should be screened for alcohol and drugs. PMID- 2593197 TI - Organ injury scaling: spleen, liver, and kidney. AB - The Organ Injury Scaling (O.I.S.) Committee of the American Association for the Surgery of Trauma (A.A.S.T.) was appointed by President Trunkey at the 1987 Annual Meeting. The principal charge was to devise injury severity scores for individual organs to facilitate clinical research. The resultant classification scheme is fundamentally an anatomic description, scaled from 1 to 5, representing the least to the most severe injury. A number of similar scales have been developed in the past, but none has been uniformly adopted. In fact, this concept was introduced at the A.A.S.T. in 1979 as the Abdominal Trauma Index (A.T.I.) and has proved useful in several areas of clinical research. The enclosed O.I.S.'s for spleen, liver, and kidney represent an amalgamation of previous scales applied for these organs, and a consensus of the O.I.S. Committee as well as the A.A.S.T. Board of Managers. The O.I.S. differs from the Abbreviated Injury Score (A.I.S.), which is also based on an anatomic scale but designed to reflect the impact of a specific organ injury on ultimate patient outcome. The individual A.I.S.'s are, of course, the basic elements used to calculate the Injury Severity Score (I.S.S.) as well as T.R.I.S.S. methodology. To ensure that the O.I.S. interdiffuses with the A.I.S. and I.C.D.-9 codes, these are listed alongside the respective O.I.S. Both the currently used A.I.S. 85 and proposed A.I.S. 90 are provided because of the obligatory transition period. Indeed, A.I.S. 90 contains the identical descriptive text as the current O.I.S.'s. The Abdominal Trauma Index and other similar indices using organ injury scoring can be easily modified by replacing older scores with the O.I.S.'s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593198 TI - Development of a statewide trauma registry. AB - In October 1986, the Pennsylvania Trauma Systems Foundation (PTSF) developed a statewide registry. Development concentrated on four major issues: 1) data elements; 2) patient selection; 3) confidential mandatory involvement for trauma centers; and 4) reporting/analysis. The overall compliance of the trauma centers was 81.5%. Documentation of prehospital run times and admission trauma scores were 21% and 70%, respectively. PTSF patients 55 years or older (27.9%) had twice the mortality as younger patients. Falls accounted for 76% of injuries to elderly patients. Finally, 42.6% of survivors had moderate to severe disabilities. Defining the "major trauma patient" is extremely difficult. A registry must have uniform quality data without undue costs. To obtain such data, maintenance of an active registry must be viewed as important as medical care, if organized trauma systems are to remain cost effective. PMID- 2593199 TI - Morbidity and mortality following fractures of the femoral neck and trochanteric region: analysis of risk factors. AB - A retrospective review of casenotes with patient review at 3 years was carried out of 405 patients who had surgery for fracture of the femoral neck (including the trochanteric region). The operative management consisted of either internal fixation (61%), hemiarthroplasty (38%), or total arthroplasty (1%). Medical complications developed in 30% of patients; surgical complications developed in 14%. The mortality rate was greater for the first 9 months after operation, but thereafter approached the rate found in the general population (matched for age and sex). Followup 3 years postoperatively recorded 50% of patients still alive. Factors associated with death within the first postoperative year included increasing age, male sex, and the presence of dementia or congestive cardiac failure. Of the survivors, 55% described unlimited range of mobility but 32% reported only poor mobility (progressive dementia being the most common cause). Factors associated with poor mobility were increasing age, female sex, placement in an institution, and the presence of dementia or cerebrovascular insufficiency. Transfer to the specialist rehabilitation ward postoperatively was associated with significantly improved survival and mobility. PMID- 2593201 TI - Retrohepatic vein injuries: experience with 20 cases. AB - The mortality for injury of the retrohepatic veins is reported to vary from 50 to 100%. The use of hepatic bypass techniques, introduced in the 1960's, has not significantly decreased this mortality. We reviewed our experience with liver injuries over a 5-year period from 1982 to 1987 to determine our results with these particular injuries. Twenty patients had retrohepatic vein injuries. There were 11 patients with penetrating trauma and nine with blunt trauma. A total of 15 patients died, for a mortality rate of 75%. Fourteen patients died intraoperatively from exsanguination and one postoperatively from sepsis. A shunt was used in an attempt to bypass the injury in ten patients, with nine deaths. In the ten remaining patients who were not shunted, there were six deaths. Thus, in ten shunted patients the mortality was 90% and in ten non-shunted patients, 60%. Our review supports other studies reporting a lower mortality by direct exposure and repair of retrohepatic vein injuries. Although total vascular occlusion of the liver may not be well tolerated in hypotensive patients, rapid application of the above approach resulted in better patient survival than the use of shunts. PMID- 2593200 TI - Impact of C-reactive protein (CRP) on surfactant function. AB - Plasma levels of the acute-phase reactant, C-reactive protein (CRP), increase up to one thousand-fold as a result of trauma or inflammation. CRP binds to phosphorylcholine (PC) in a calcium-ion dependent manner. The structural homology between PC and the major phospholipid component of surfactant, dipalmitoyl phosphatidylcholine (DPPC), led to the present study in which we examined if CRP levels might be increased in patients with adult respiratory distress syndrome (ARDS), and subsequently interfere with surfactant function. Our results showed that CRP levels in the bronchoalveolar fluid (BALF) was increased in patients with ARDS (97.8 +/- 84.2 micrograms/mg total protein vs. 4.04 +/- 2.2 micrograms/mg total protein in normals). Our results show that CRP binds to liposomes containing DPPC and phosphatidylglycerol (PG). As a result of this interaction, CRP inhibits the surface activity of a PG-DPPC mixture when tested with a Wilhelmy surfactometer or with the Enhorning pulsating bubble apparatus. Furthermore, the surface activity of a clinically used surfactant replacement, Surfactant TA (2 mg/ml), was also severely impaired by CRP in a dose-dependent manner (doses used ranging from 24.5 to 1,175 micrograms/ml). In contrast, human serum albumin (HSA) at 500 and 900 micrograms/ml had no inhibitory effect on Surfactant TA surface activity. These results suggest that CRP, although not an initiating insult in ARDS, may contribute to the subsequent abnormalities of surfactant function and thus the pathogenesis of the pulmonary dysfunction seen in ARDS. PMID- 2593202 TI - Avalanche trauma. AB - Medical aspects of avalanche accidents have apparently not been studied in the American literature. Records from the Utah Avalanche Forecasting Center (UAFC) for the period 1982-1987 were reviewed and compared with similar data from Europe and Canada. One hundred forty-five avalanches involving 188 individuals were reported to the UAFC. Ninety-one (48%) people were caught, of whom 21 required medical attention. Twelve of the 91 died (13%) and nine were injured (10%). Eleven of 12 nonsurvivors and four of nine survivors were completely buried. Evidence of major blunt trauma was present in nine of ten nonsurvivors and all nine survivors. Asphyxia and blunt trauma were the most common causes of death; hypothermia appeared to have played only a minor role. These findings were similar to results obtained in Europe and Canada. PMID- 2593203 TI - Jefferson fracture in a 2-year-old child. AB - Fractures of the atlas vertebra in the pediatric population are very rare, yet must be considered when evaluating a child with neck pain and torticollis. Plain radiographs and computerized tomography should be used in conjunction to confirm the diagnosis. PMID- 2593204 TI - Selective hepatic artery embolization as an adjunct to liver packing in severe hepatic trauma: case report. AB - Two cases of severe hepatic injury in which bleeding continued despite liver packing are presented. Superselective hepatic artery embolization was used to control the remaining hemorrhage. Embolization is a useful adjunct to liver packing that will decrease mortality in severe hepatic trauma. PMID- 2593205 TI - Intraoperative cardiac sampling following penetrating wounds: a technique for early detection of traumatic intracardiac shunts--case report. AB - Intracardiac shunts complicating penetrating heart wounds may be unrecognized during the early postoperative period due to the insensitivity of noninvasive diagnostic tests. This case demonstrates the value of intraoperative cardiac sampling for oxygen saturation to identify an otherwise occult aorta-right ventricular fistula secondary to a precordial stab wound, ultimately progressing to a 1.9:1 shunt requiring operative repair. PMID- 2593206 TI - Relapse prevention in psychoeducational groups for compulsive crack cocaine smokers. AB - The paper presents a model of relapse prevention that utilizes metaphor, education, and psychodynamic and cognitive-behavioral principles in psychoeducational groups for compulsive crack cocaine smokers during inpatient detoxification. Relapse prevention teaches engagement in preventive alternative behaviors after inpatient detoxification. Clinical interventions impress patients with the nature of their psychological vulnerability to internal and external dangers and the importance of aftercare treatment post detoxification to receive needed support negotiating high risk situations. The paper provides a detailed description of the group process and of the actual interventions the clinician utilizes, thereby expanding clinical options on what to do and say when educating patients on relapse. Interventions prepare patients to negotiate the numerous high risk situations they will encounter after inpatient treatment that could easily trigger relapse. Psychoeducation provides patients with a cognitive and intellectual framework in which to understand the process of psychotherapy, the difficulties regulating affect and self esteem, and how aftercare treatment addresses their psychological problems and decreases chances of relapse. PMID- 2593207 TI - DMI-measured defenses and HIV-related risk behaviors in i.v. compared to non-i.v. substance abusers. AB - The Defense Mechanism Inventory (DMI) and The Risk Behavior Inventory (RBI) were administered to substance abusers hospitalized on a drug detoxification service. The groups were categorized on the basis of self-reported IV versus non-IV substance abuse. Significant between-group differences were obtained on the DMI and RBI. The non-IV group responded less often than the IV group with the Turning Against Object (TAO) response option, resulting in higher scores when Turning Against Self (TAS), Reversal (REV), Principalization (PRN) and Projection (PRO) were summed into a single score. Significant within-group differences were obtained for DMI response levels and defenses. Both groups relied less on TAO at the thought level and more on PRN and REV as primary defenses. The IV group reported twice as many risk behaviors as the non-IV group and risked HIV exposure through needle use and sexual transmission modes. Consideration was given to the role of principalization and denial within the addicted individual's defense structure and the relationship of these defenses to HIV-related risk behavior. PMID- 2593208 TI - Occupational distress disorder (ODD). PMID- 2593209 TI - Outcome of a unique youth drug abuse program: a follow-up study of clients of Straight, Inc. AB - A unique feature of the 12-hour per day Straight, Inc., program is temporary placement of the client with the family of a client who has progressed further in the program. Eighty-five (85) percent of the clients reported that their drug use was less at follow-up than when they started in the program. Follow-up reports by parents indicated their impression of a statistically significant decrease in the proportion of clients who were still involved in substance use. Statistically significant improvement at follow-up was also reported by the clients on seven of eight other selected outcome criteria (e.g., suicidal thoughts, physical violence, number of arrests, etc.). The majority of the clients reported that they were "satisfied" with the program (70%), that the program "helped" them (74%), and, specifically, that the program helped them with their relationship with their parents (69%). PMID- 2593210 TI - [Effect of radiation on the fungal flora of the external ear canal]. AB - A mycological study of external ear canals was performed in 40 patients with head and neck cancer to observe the radiation effect on the fungal flora in external ear canals. The control group consisted of 30 non-cancer patients. The findings were: 1. More Candida sp. and Aspergillus sp. were noted in cancer patients than control group and C. albicans were also found, which didn't exist in normal persons. 2. There were opportunistic fungal flora, Candida sp. and Aspergillus sp., in at least one side of external ear canals in 32.5% of the post-irradiated patients who had aseptic external ear canals before the radiation therapy. The reasons we inferred that the patients with head and neck cancer during the radiation therapy were predisposed to otitis externa, in addition to radiation injury to the canal skin, were: 1. The different fungal flora in external ear canals of patients with head and neck cancer before the radiation therapy. 2. The changes of fungal flora after the radiation therapy. PMID- 2593211 TI - Characterization of cytotoxicity and R-plasmid in Salmonella krefeld. AB - From 1981 to 1984, 254 isolates of Salmonella krefeld were isolated from newborns and infants with acute gastroenteritis in southern Taiwan. All the crude enterotoxin preparations of S. krefeld caused the cytotoxic elongation reaction in Chinese hamster ovary K1 (CHO-K1) cells. Cytotoxic enterotoxin was also produced by S. krefeld inducing Vero cells to round up and appear partially detached from the culture plate. It was noted that S. krefeld showed internalization and multiplication in CHO-K1 cells. S. krefeld exhibited 12 different resistant patterns. And the predominant patterns were found to be resistant to kanamycin and ampicillin (Ka-Amr), and resistant to kanamycin, ampicillin, chloramphenicol and tetracycline (Ka-Am-Cm-Ter). It was found that two distinct plasmids of 34 megadalton (Md) and 120 Md were commonly present in these strains. S. krefeld haboured 34 Md and 120 Md R-plasmid, which conferred resistance to Ka-Amr and Ka-Am-Cm-Ter, respectively. From the resistance transferred patterns, Ka-Amr was the most common resistance among transconjugants. The frequency of transfer of the 34 Md R-plasmid (2.71 x 10(-3) transconjugants/donor cell) from S. krefeld to E. coli K-12 14R525 was 20 times higher than that of the 120 Md R-plasmid (1.48 x 10(-4) transconjugants/donor cell). In analysis of the restriction endonuclease digest of the 34 Md plasmid obtained from different bacterial sources, their specific identical DNA fragment pattern suggested that the outbreak infection due to S. krefeld had a common origin. PMID- 2593212 TI - [A study of the effect of patient load and diseases upon resident training in a family medicine clinic]. AB - Patient appointments and scheduling of patients and physicians are the first step in family medicine practice. The goals of outpatient services are to train the family physicians, to provide comprehensive and continuing health care for the family and its members. We evaluated the effect of the appointment system upon residents' training in a family medicine clinic of the Kaohsiung Medical College Hospital. The results were as follows: during the period between Aug. 1985 and Nov. 1986, a total of 2,220 patients and 5,891 out-patient encounters was recorded in this module. The subject age was mostly in the range of 16-64 years for all trainees. The distribution of the chronic diseases was relatively even for all except two trainees. For 4 residents, there were 40-60% more than the ideal patient numbers per session. This abnormal situation interferes with the normal functioning of family medicine clinics. The provocative results of this study suggest at least two important avenues for improvement. The first is to modify the appointment system. The second is to schedule the ideal amount of patients and kinds of diseases in order to provide comprehensive and continuous care for the family and its members. PMID- 2593213 TI - Biomechanical study of KMC transspinous process wiring technique with Luque segmental spinal instrumentation. AB - An in vitro experiment was designed to evaluate the mechanical properties of a new trans spinous process wiring method (KMC method) for segmental spinal instrumentation by using the goat spine model and double Luque L rods. Specimens were tested by a universal testing machine with the cyclic 3-point bending load. Instrumentation with Wisconsin trans spinous process button & wire system was also tested for comparison. The experimental results show no difference in maximal bending load between two methods, but the KMC method provided greater rigidity in forward bending and less incidence of wire breakage. PMID- 2593214 TI - [Treatment of elbow contracture]. AB - The most common sequela of the elbow joint after injury is decreased range of motion, i.e. elbow contracture. From January 1986 to July 1987, the Orthopaedic department of Kaohsiung Medical College collected data of 10 elbow contracture on 9 cases. Treatment included capsulotomy and joint debridement with immediate postoperative rehabilitation. This paper reports the clinical follow up results with an average time of 7 months after the operation. Range of motion increased 50 degrees on the average. No residual pain was complained. Activity of daily living was improved and the results were satisfied. PMID- 2593215 TI - [Blood routine tests in capillary blood compared to those of venous blood]. AB - When the venipuncture is difficult, should the blood routine tests be performed on capillary blood? Are there any differences in blood routine tests between capillary blood and venous blood? Many studies have been made of infants before our study, but there are few studies of adults. For the purposes of this study, we compared blood routine tests in capillary blood with those of venous blood in adults. Capillary blood and venous blood were drawn at the same time from 50 adults to estimate the values of blood routine tests. Specifically, blood specimens were drawn to estimate RBC, WBC, Hb, Hct, MCV, MCH and MCHC values by coulter counter model S7, while platelet value was estimated by ULTRA FLO 100. The results are presented follows: (1) The differences are non-significant in RBC, WBC, Hb and MCH between the venous blood [453.74 +/- 85.4) x 10(4)/cmm, 8290 +/- 4074/cmm 13.53 +/- 2.42 (gm%), 30.23 +/- 2.55 (pg] and the capillary blood [463.14 +/- 94.57) x 10(4)/cm 8182 +/- 4268/cm, 13.82 +/- 2.61 (gm%), 30.12 +/- 2.21 (pg]. p greater than 0.05. (2) The values of the Hct and MCV in capillary blood (44.02 +/- 7.78 (%), 95.34 +/- 7.33 (fl] are significantly higher than those of venous blood (40.64 +/- 6.83 (%), 89.94 +/- 6.94 (fl]. p less than 0.05. (3) The values of the platelet and MCHC in venous blood (29.29 +/- 10.5) x 10(4)/cmm, 33.17 +/- 1.09 (%] are significantly higher than those of capillary blood (18.44 +/- 8.1) x 10(4)/cmm, 31.38 +/- 1.01 (%]. p less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593216 TI - Sistrunk revisited: a 10-year review of revision thyroglossal duct surgery at Toronto's Hospital for Sick Children. AB - The definitive surgical management of thyroglossal duct cysts (TGDC) was elucidated by Sistrunk in 1920. However, the procedure is often poorly performed. We reviewed the charts of 143 patients managed for TGDC at the Hospital for Sick Children. Toronto, between 1978-1988. These patients underwent 214 surgical procedures at HSC and elsewhere for cure. One hundred and five patients needed only one procedure. Thirty-eight patients had recurrent disease. These needed 109 procedures for cure. Inadequate surgery was the direct cause of recurrence. Areas of surgical failure included misdiagnosis, inadequate hyoid bone resection and persistent infra or suprahyoid tract remnants. Representative case samples are outlined with clinical, surgical and pathologic correlation. We recommend performing the complete, classic Sistrunk procedure for all cases of TGDC. PMID- 2593217 TI - TMJ dysfunction: surgical management and reconstruction. AB - In this paper the surgical management of TMJ dysfunction-ankylosis and arthropathies-is described. The surgical techniques and the necessity of wide exposure are pointed out. Only thus are correct reshaping of the condyle, repair of the disc and radical resection of ankylotic bone tissue possible. The indication for prosthetic substitution to be interpositioned in cases with discal atrophy and perforation is discussed. There were no cases of facial paresis and no recurrence of ankylosis. The results, in regard to the functional aspects, confirm the efficiency of the methods described. PMID- 2593218 TI - Cancer of the larynx: the northern Alberta experience. AB - Three hundred and seventy-nine cases of laryngeal cancer diagnosed between the years 1970 to 1984 were compiled and analyzed with respect to pathology, staging, treatment and outcome. The most common cancer reported was squamous cell carcinoma. Also reported were verrucous carcinoma, spindle cell carcinoma and one case of chondrosarcoma. Males comprised 88% of the patients, females 12%. The average age of the patients was 59 years. The most common lesion reported was stage I squamous carcinoma of the laryngeal glottis. The study will present data on the treatment and outcome of these cases of laryngeal cancer. PMID- 2593219 TI - Perception of pre-vocalic and post-vocalic consonants produced by tracheoesophageal speakers. AB - The purpose of this project was to investigate the perception of consonant-vowel consonant (CVC) stimuli produced by four tracheoesophageal (TE) speakers. Stimuli were representative of five phonetic manner classes (stop, fricative, affricate, nasal, and liquidglide). Twelve naive normal-hearing young adults served as listeners. Stimuli were presented via headphones and listeners were prepared and analyses of the data were conducted for individual speakers and for the entire group. The listeners' perceptual judgments were analyzed for each manner of production by phonetic context. Based on statistical analyses of the data obtained, all four speakers were perceived by listeners to produce post-vocalic consonants with significantly better intelligibility. PMID- 2593220 TI - Submandibular sialolithiasis: transoral excision. AB - In 17 cases the author has removed intraglandular submandibular calculi by an oral route utilizing blunt soft tissue dissection after an incision of the mucosa only. General anesthesia is used and the patient discharged after an overnight stay. No complications were encountered. All patients were back on full diet in 48 hours. PMID- 2593221 TI - Revision of a vertical tracheotomy scar using the W-plasty technique. AB - Repair of a vertical tracheotomy scar using a W-plasty technique is discussed, and an illustrative case is presented. The indications and technique of the W plasty repair are reviewed. The advantages over the classical running Z-plasty in this type of scar repair are outlined. PMID- 2593222 TI - Distortion product emissions and sensorineural hearing loss. AB - Distortion product emissions (DPEs) are intimately linked to normal outer hair cell function. Outer hair cell function is itself intimately linked with normal auditory thresholds. We sought to correlate frequency-specific DPE measurements with auditory thresholds, in seven frequency regions from 700 Hz to 6 kHz, in each of 21 ears. Eleven of these ears had thresholds below 25 dB SPL at every test frequency, whereas 10 ears demonstrated some degree of purely sensorineural hearing loss. An analysis of the correlation between DPE measurements and sensory thresholds suggests that DPE measures can predict frequency-specific auditory thresholds to within 10 dB over a range of sensory thresholds from 0 dB SPL to 60 dB SPL. Distortion product emissions promise to provide an objective, non invasive measure of sensory thresholds. The clinical value of DPE measurement is enhanced by that fact that it is brief and requires minimal subject participation. A clinical test based on the DPE measurement will not displace conventional audiometry or auditory brain stem response measurement. It promises to provide new information about cochlear function to both the clinician and auditory physiologist. PMID- 2593224 TI - Stapedectomy as an outpatient procedure. AB - Many ENT surgeons are accustomed to perform stapedectomy in a hospital setting. We present our results with 19 patients on whom stapedectomies were performed in an outpatient setting. In respect of hearing gain and complications, our results are not significantly different from the results of those series of stapedectomies performed in hospital. Thus, we believe that stapedectomy can be performed as an outpatient procedure. PMID- 2593223 TI - Acute otomastoiditis in the leukemic child. AB - We report three leukemic children undergoing chemotherapy who presented severe otomastoiditis with sensorineural hearing loss. They all developed a sub-total perforation of the tympanic membrane within a few days and one child sustained necrosis of the middle ear mucosa and diffuse destruction of the mastoids. Hearing tests showed severe sensorineural hearing loss in the ears affected. The evolution of the disease is reminiscent of a preantibiotic era pathology known as "acute necrotizing otitis media". A management program is proposed for the treatment of otitis media in leukemic patients receiving chemotherapy. PMID- 2593225 TI - Sternocostoclavicular hyperostosis. PMID- 2593226 TI - [36th meeting of the Japanese Society of Anesthesiology. Yamaguchi, 13-15 April 1989. Abstracts]. PMID- 2593227 TI - [Assay methods for Ca ion in immunocytes using Ca ion-sensitive fluorescent reagents]. PMID- 2593228 TI - [A study of a regional lymph node metastasis in a well-differentiated thyroid carcinoma]. AB - Forty-eight patients with a well-differentiated thyroid cancer that occupied unilateral lobe were given, a modified radical neck dissection (unilateral or bilateral). After an examination of their lymph nodes, a retrospective analysis showed that the metastasis extended to the lateral cervical lymph node on the ipsilateral neck in 43.8% of all cases, and to at least the paratracheal lymph node on the contralateral neck in 27.2% of all cases. Therefore a bilateral modified radical neck dissection is needed surgical treatment for such patients. PMID- 2593229 TI - [Clinical study of taste abnormalities in advanced lung cancer cases]. AB - Taste recognition thresholds for four basic tastes, sweet, salty, and bitter, have been examined in 36 advanced lung cancer patients to identify the presence or absence of taste abnormalities in such patients. Twenty-six untreated lung cancer patients, or 65.3%, demonstrated an abnormal taste threshold for at least one of the 4 taste, a result varying significantly from suitable controls (p less than 0.05). Among the total 36 lung cancer patients, the number of those showing a threshold abnormality was no different between the smoker and non-smoker groups, though abnormalities were higher in the low serum zinc level group than in the normal serum zinc level group (p less than 0.05). We also observed transient threshold elevations after chemotherapy including Cisplatin. Thus, it is thought that taste abnormalities are more prevalent in advanced lung cancer patients. PMID- 2593230 TI - [Clinical study of multiple primary cancers including lung cancer]. AB - Out of a total of 506 lung cancers treated between 1977 to 1988, a total of 27 (5.3%) multiple primary cancers were uncovered. The patients consisted of 20 males and 7 females and their average age was 67 (48-81) years. The frequency seen in the histological type of patient with multiple primary cancers was the same as that seen in their background lung cancers. Twenty-one (78%) patients were smokers. Thirteen patients (45%) had a family history of cancer. Two cases had 3 family members who had a cancer history. The tumor DNA contents of 2 cases with multiple primary cancers were analyzed. In both cases, the DNA indices were found to differ between the first and the second cancer. Thus, it may be possible to identify multiple primary cancers by determining the tumoral DNA content. PMID- 2593231 TI - [Brain metastases from carcinomas of the digestive organs--a comparative study with those from pulmonary carcinomas]. AB - During the past 11 years, we have experienced 7 cases of a metastatic brain tumor with the primary lesion in the digestive organs. Their clinical courses were retrospectively compared with those of 19 cases with a brain metastases from pulmonary carcinomas. Leptomeningeal carcinomatosis was found in 2 patients of the former group but none in the latter. Six out of 7 brain metastases in the former group were found to have averaged 13 months before their appearance after the diagnosis of the primary lesion. In contrast, 14 out of 19 patients in the latter group had an onset with symptoms of a brain metastasis. The average survival after intracranial surgery on the metastatic tumor was 174 days for the former group and 268 days for the latter. The prognosis of a brain metastasis from a carcinoma of the digestive organ appears to be extremely probable. PMID- 2593232 TI - [A clinicopathological study of recurrent gastric cancer cases treated by a resection of the remnant stomach]. AB - Seventeen cases of a recurrent gastric cancer that were treated by a resection of the remnant stomach have been studied retrospectively. For first management 12 cases were given a Billroth 2 procedure, 4 cases a Billroth 1 procedure and 1 case a fundectomy. For the recurrent cancer, 13 cases were given a total resection of the gastric remnant and 4 cases a partial resection. The overall mortality rate was 12% and the survival rate was 58% at 1 year, and 8% at 5 years. We thus have concluded that a resection of the remnant stomach should be carried cut in cases of a recurrent gastric cancer whenever possible. PMID- 2593233 TI - [Histological malignancy grading of oral squamous cell carcinomas]. AB - A modification of Jakobsson's criteria that determines the mode of cancer invasion (Yamamoto, 1982) has been reported to be useful in predicting the prognosis in patients with an oral squamous cell carcinoma. In this retrospective study, a five-factorial grading system of the histological malignancy (+ the differentiations, the nuclear polymorphism, the mitoses, and the cellular response) was evaluated in relation to clinical course of each patient. RESULT: 75 cases were classified into four grades from Grade 1, the lowest malignancy, to Grade 4, the highest malignancy. The percentage metastases was 10, 24, 54, and 75% for each grade, respectively. The percentage of survival was 75, 75, 35, and 25% for each grade, respectively. From these results, this grading system was seen to have a close-correlation with the clinical course of each patient. PMID- 2593234 TI - [A case of carcinoma of the ileum diagnosed as an adenocarcinoma]. AB - A 65-year-old female with a history of cancer of the uterine body and a strong family history of cancer, was admitted with abdominal pain and anemia. During roentgenographic examination of the small intestine, a tumor was recognized about 25 cm from the ileocecal valve, leading us to suspect a carcinoma of the ileum. A colonoscopy demonstrated a constricting, ulcerated lesion, with a round wall: and a subsequent biopsy proved that the patient had a moderately differentiated adenocarcinoma. At surgery, a tumor, measuring 52 x 50 mm, was found to have infiltrated the serosa with a metastasis to the mesenteric lymph node. PMID- 2593236 TI - [Coagulation and fibrinolysis associated with contact phase in plasma with high molecular weight kininogen deficiency]. AB - Congenital deficiency of high molecular weight kininogen (HMWK), first reported by Saito et al. in 1975, is a rare disorder with homozygous defect of HMWK and only 14 cases have been reported so far. Prolonged partial thromboplastin time and depressed intrinsic fibrinolytic activity in plasma interacted with negatively charged surface were characterized in these patients without any bleeding problem. On the other hand, patients associated with hemorrhagic disorder, such as haemophiliacs, showed a markedly prolonged partial thromboplastin time but normal intrinsic fibrinolytic activity. These results give us a important suggestion on our understanding of why haemophiliacs bleed and why HMWK deficient patients do not. In immunological studies with specific antisera directed against human plasma HMWK and prekallikrein, HMWK in present in normal plasma in free form and a complexed form with prekallikrein, and whole prekallikrein in present in a complexed form with HMWK. This result is associated with diminished level of prekallikrein in plasma of patients with congenital HMWK deficiency. According to above-mentioned our experimental results and some reports, it is speculated that the deficiency of HMWK with normal level of prekallikrein is acquired. PMID- 2593235 TI - [DNA analysis for the kininogen gene of patients with kininogen deficiency in Japan]. AB - The kininogen (KGN) gene status was examined in 4 families with both high molecular weight (HMW) and low molecular weight (LMW) KGM deficiency and one family with only HMW-KGN deficiency reported in Japan. No abnormal HMW-KGN or LMW KGN was detected in those with these deficiencies by immunoblot analysis using monoclonal antibodies (HKG-H12, HKG-L7, HKG-L17) for human HMW-KGN. HMW-DNA prepared from peripheral blood leucocytes was digested with endonuclease, EcoRI, Bam HI, Hind III, Sca I, Bg1II, Xba I, Msp I, Pst I, Hpa I, PvuII, HaeIII, Rsa I, Alu I, or Taq I, and studied by Southern blot analysis with human LMW prekininogen cDNA (phKG 36) as a probe. A gross deletion or insertion of the KGN gene was not detected in those with both HMW- and LMW-KGN deficiencies. On the other hand, partial defect in intron 7 (G) was found in those with only HMW-KGN deficiency, suggesting that this defect might be related to abnormality of the alternative RNA splicing events for HMW-prekininogen mRNA. PMID- 2593237 TI - [Changes of high molecular weight kininogen in various states]. AB - Changes of high molecular weight kininogen (HMW-K) clotting activity, antigen and cleavage in the plasma in the health and various diseases were studied. In 20 healthy individuals clotting activity of HMW-K, as measured by APTT one stage method, was 99 +/- 12% (male) and 84 +/- 15% (female). Antigen as measured by Laurell method were 106 +/- 24% (male) and 91 +/- 21% (female). In 35 patients with disseminated intravascular coagulation (DIC), both activity (78 +/- 33%) and antigen (69 +/- 31%) were statistically lower than those in normal individuals (p less than 0.01). In DIC both activity and antigen of HMW-K was correlated with serum albumin level. These results suggest that the cause of the lower level of HMW-K in DIC especially with septicemia is the result of lower production rather than consumption. In vivo cleavage of HMW-K was detected in plasma of a patient with septicemia and DIC by immunoblotting. The change of HMW-K was also assessed in other pathological states including liver cirrhosis, collagen disease, cardiopulmonary bypass and pregnant women. PMID- 2593238 TI - [Physiopathology of kinin forming system in reproduction]. AB - We studied contact factors and kinin-kallikrein in normal non-pregnant and pregnant women, FXII deficient toxemia and DIC. The results obtained are as follows: 1. The levels of plasma prekallikrein, high molecular weight kininogen, kallikrein inhibitor, and C-1 INA were gradually decreased at delivery, and the levels of kallikrein like activity and bradykinin were increased during pregnancy and at the time of parturition. These facts indicate that kinin kallikrein systems played important role in uterine contraction. 2. The levels of contact factors (FXII and FXI) were lower at delivery than those of term. 3. In rat uterus, specific binding of bradykinin was observed by the method of radio receptor assay in the pelet of 10,000 X g fetal membranes, and its activity was 38%. 4. A synthetic kallikrein inhibitor (OS-291, MS) and bradykinin antagonist inhibited completely spontaneous uterine contraction of Wistar rats during delivery. 5. In the case of FXII deficiency, the levels of plasma prekallikrein, high molecular weight kininogen were normal, but at delivery, these levels were lower than those of term. The levels of kallikrein like activity which was half of normal parturition level was increased at parturition. 6. In cases of DIC (17) and severe toxemia (22), plasma prekallikrein levels were lower than the normal controls. The decrease was due to consumption of plasma prekallikrein to kallikrein activation. PMID- 2593239 TI - [Immunological characterizations of adult T cell leukemia cells]. AB - Profiles of antigens, associated with activation of normal T cells, on adult T cell leukemia (ATL) cells obtained from ATL patients with various clinical stages (acute, chronic, smoldering), were examined. The expressions of Ki 67, OKT 9 and CD 38 antigens were correlated with the spontaneous 3H-thymidine uptake and also with the severities of the disease. CD 25 and CD 28 antigens were expressed on ATL cells from all clinical stages. A loss of CD 7 antigen was observed in peripheral blood ATL cells. HLA-DR antigen was detected on smoldering and chronic ATL cells, but the antigen was not present on acute ATL cells. Surprisingly, both of these antigens were present on lymph-node ATL cells, which proliferate 15-50 fold more than peripheral blood ATL cells do. These findings confirmed that ATL cells preferentially proliferate in lymph nodes, and CD 7 and HLA-DR antigens might contribute to the proliferation. A cDNA named pLD 78 was isolated from a library constructed from the poly (A)+RNAs of tumor promoter and mitogen stimulated human tonsillar lymphocytes, using a differential hybridization technique. pLD 78 DNA sequence codes for a polypeptide consisting of 92 amino acid residues, including a putative signal sequence. A computer search with the National Biomedical Research Foundation library showed that this proteis had homologous sequences with several proteins, which are involved in inflammation and tumorigenesis. The highest homology was found with mouse macrophage inflammatory protein (MIP).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593240 TI - [Immunologic deficiency in HTLV-I infection]. PMID- 2593241 TI - [Hemostatic changes before and after the onset of disseminated intravascular coagulation]. AB - We performed a blood coagulation study during the course of disseminated intravascular coagulation (DIC) in 34 patients with hematological malignancies. Risk factors of DIC such as increasing tumor mass, anti-tumor therapy and severe infections were frequently observed at onset of DIC, and influenced the prognosis of DIC. Before the onset of DIC, the DIC score and FDP value were slightly elevated, and they were significantly increased after the onset of DIC. Before the onset of DIC, the level of fibrinogen was significantly increased but it was decreased after the onset of DIC. These hemostatic abnormalities continued for about 2 weeks. Patients with DIC showing prolonged APTT and PT had a poor prognosis. The abnormalities of PT, FDP, fibrinogen, DIC score, FDP-D-dimer and fibrinopeptide A were significantly greater in DIC than in Pre-DIC defined as the period one week before the onset of DIC. FDP-D-dimer was also higher in Pre-DIC patients than in those without DIC. Although protein S and C 4 b binding protein were not decreased in DIC or Pre-DIC, Protein C activity decreased during the course of DIC, suggesting that FDP-D-dimer and Protein C activity were useful for diagnosis of Pre-DIC and DIC. PMID- 2593242 TI - [Cytological findings of the cerebrospinal fluid at diagnosis of acute lymphocytic leukemia in children--effect of remission induction chemotherapy]. AB - Cytological examination of the cerebrospinal fluid (CSF) was performed in 88 children with acute lymphocytic leukemia at the time of initial diagnosis (54 cases), during (day 1-15, 17 cases) or after (day 37-58, 17 cases) the remission induction chemotherapy. Leukemic cells were found on cytological examination in 23 cases (42.6%), 5 cases (29.4%) and 2 cases (11.8%), respectively, and the incidence of central nervous system (CNS) leukemia had a tendency to decrease during the induction chemotherapy. The follow-up study of 15 cases of CNS leukemia at diagnosis revealed that the leukemic cells in CSF had decreased within 2 weeks and then disappeared after the induction chemotherapy. These findings indicate the therapeutic effect of induction chemotherapy including prednisolone on subclinical CNS leukemia at diagnosis. PMID- 2593243 TI - [Cytogenetic studies of healthy HTLV-I carriers (Report 1): Cytogenetic studies of an ATL family]. AB - The chromosome 14q11 anomaly has been reported to be specific to adult T-cell leukemia (ATL) and this anomaly has also been confirmed in preleukemic state of ATL (pre-ATL) patients though the frequency is low. In an attempt to clarify if the same chromosome aberrations could be found also at the stage of HTLV-I carrier and if there is any cytogenetic difference from non-HTLV-I carriers, a cytogenetic study of lymphocytes stimulated with phytohemagglutinin in three HTLV I healthy carriers and three non-HTLV-I carriers in an ATL family was performed. The results were as follows. 1. In three HTLV-I carriers, 7 of 311 cells examined (2.3%) showed chromosome aberrations, and 4 cells (1.3%) had 14q11 anomaly. 2. In three non-HTLV-I carriers, 4 of 260 cells examined (1.5%) showed chromosome aberrations, whereas no cells had 14q11 anomaly. These findings suggest that 14q11 anomaly is already present at the stage of HTLV-I carrier and seems to be an important cytogenetic clue to the pathogenesis of ATL. PMID- 2593244 TI - [Activity of procoagulant and fibrinolysis in homogenate of leukemic cells]. AB - We examined activities of procoagulant and fibrinolysis in homogenate of leukemic cells. Procoagulant activity (PCA) was increased in patients with acute myelocytic leukemia (AML) and acute promyelocytic leukemia (APL), but it was significantly decreased in patients with chronic myelocytic leukemia (CML) and adult T cell leukemia. In CML, PCA was increased in the blastic phase. Plasminogen activator activity (PLGAA) was also increased in patients with AML, APL and acute lymphocytic leukemia (ALL) associated with disseminated intravascular coagulation (DIC). Elastase-like activity, trypsin-like activity and chymotrypsin-like activity (CTLA) were increased in those with myelocytic leukemia, but they were low in those with lymphocytic leukemia. PCA, PLGAA and CTLA were significantly higher in patients with DIC than in those without DIC. Measurement of procoagulant and fibrinolytic activity in leukemic cells homogenate may be useful not only for studying hemostatic abnormalities but also for classification of leukemic cells. PMID- 2593245 TI - [Study on pathophysiology of the myelodysplastic syndromes (MDS)--pattern of dysmegakaryopoiesis related to leukemic transformation]. AB - A series of 116 patients with MDS consisted of 74 cases of RA, 10 cases of RARS, 14 cases of RAEB, 9 cases of RAEB-T and 9 cases of CMML, were studied on the quantity and morphological abnormalities of megakaryocytes in relation to over all survival and leukemic change. The amount of megakaryocytes was graded into four groups; marked hypoplasia (O), moderate hypoplasia (L), normoplasia (N) and hyperplasia (H), RA cases showed heterogeneous pattern; containing 14 cases (18.9%) of group (O), 18 cases (24.3%) of group (L), 31 cases (41.9%) of group (N) and 11 cases (14.9%) of group (H). RARS, RAEB, RAEB-T and CMML cases were classified into group (N) or group (H). The heterogeneous pattern of RA did not relate to leukemic change, but over all survival tended to be shorter in group (N) cases. A significant number of young female cases of RA were involved in group (O). Morphological abnormalities of MDS megakaryocytes were classified into five types; I, mononuclear micromegakaryocytes, II, binuclear micromegakaryocytes, III, mononuclear small megakaryocytes, IV, multiseparated nuclear megakaryocytes and V, megakaryocytes with bizzare nuclei. RAEB and RAEB-T cases uniformly showed marked dysmegakaryopoiesis ranging from type I to V. whereas RA, RARS and CMML cases showed mild dysmegakaryopoiesis. Only five cases (6.4%) of RA cases had type I micromegakaryocytes. Eight RA cases with type I on diagnosis or obtaining it during the clinical course tended to develop acute myeloid leukemia (5 cases) or to transform to RAEB sooner or later. In two cases of RAEB in which hematological improvement was obtained with low dose cytosine arabinoside regimen, disappearance of type I micromegakaryocytes was noted. A female case with 5q-anomaly surviving more than 10 years showed marked megakaryocyte hyperplasia and almost exclusively type III and IV megakaryocytes. These findings indicated that pattern of dysmegakaryopoiesis, especially appearance of type I, was closely related to leukemic change in MDS. Thus quantitative and qualitative evaluations of MDS megakaryocytopoiesis seemed important to understand the further heterogeneity of pathophysiology in MDS subtypes. PMID- 2593246 TI - [Acute myelofibrosis terminating in acute myelomegakaryoblastic leukemia]. AB - We report a case of acute myelofibrosis (AMF) developing into acute myelomegakaryoblastic leukemia. A 33-year-old woman was admitted to our hospital because of fever and chest pain. On physical examination, hepatosplenomegaly was not noticed. Pancytopenia and a small number of blast cells were observed in the peripheral blood. Poikilocytosis was not detected. Bone marrow examination revealed dry tap on aspiration, and moderate increase in reticulin fiber on biopsy. The diagnosis of AMF was made. Eight months later, blast cells markedly increased. Surface marker was investigated and MCS-2 (CD13), C17 (CDw41) and P2 (CDw41) were found to be positive. Electron microscopic examination revealed that blast cells were composed of PPO-positive cells and MPO-positive cells. Based on these findings, it was considered that the patient developed acute myelomegakaryoblastic leukemia. Recently AMF is thought to be a state to have the ability to develop into various types of acute leukemia. Adequate therapy may be required before the development of leukemia. PMID- 2593247 TI - [Acute biphenotypic leukemia followed by two color flow cytometry]. AB - In this paper is reported a case of acute biphenotypic leukemia who was treated by chemotherapy and pursued its effect by two color flow cytometry. A 33-year-old male patient was admitted due to fever and general fatigue and diagnosed as acute leukemia by hematological findings. Surface markers were investigated to find positive reaction of Leu 12 (CD19), J 5 (CD10), My 7 (CD13) and My 9 (CD33), in which Leu 12 and My 9 were simultaneously expressed on the same blast cells by two color flow cytometry. He was treated with daunorubicin, enocitabine, mercaptopurine, vincristine, and prednisolone to obtain partial remission. Then, he was administered L-asparaginase, doxorubicin, vincristine and prednisolone to reach complete remission. The effect of chemotherapy was investigated by not only bone marrow puncture, but also by two color flow cytometry. From the findings in this case, the two flow cytometry was proved to be a useful tool for not only diagnosis of acute mixed leukemia, aut also the judgement of the effect of treatment. PMID- 2593248 TI - [Castleman's lymphoma associated with swelling of pancreas and pancytopenia]. AB - A 73-year-old male was admitted because of slight fever. Systemic lymphadenopathy, polyclonal hypergammaglobulinemia, swelling of pancreas and submaxillary gland and progressing pancytopenia probably by immune mechanism were observed. Histological examination of lymph node showed no destruction of the structure and mild capillary proliferation in the follicle centers. Between follicles, many immunoblasts and mature plasma cells which were polyclonal and mild capillary proliferation were recognized. He was diagnosed as having multicentric Castleman's lymphoma. Administration of prednisolone 10 mg per day improved his symptoms and laboratory data. Then he has been followed up. Referring to the literatures, we discussed the relation between multicentric Castleman's lymphoma and the related diseases. PMID- 2593249 TI - [Disseminated intravascular coagulation related to atherosclerosis and aneurysm of aorta: successful management with subcutaneous self injection of heparin sodium]. AB - We described here a seventy-one year-old male, who had repeated disseminated intravascular coagulation related to atherosclerosis and aneurysm of the aorta, and was successfully treated with self-subcutaneous injection of heparin sodium. He developed gingival bleeding and purpura in 1977. He was first treated with prednisolone (30 mg/day) and ACTH-Z under the diagnosis of idiopathic thrombocytopenic purpura associated with chronic thyroiditis, since platelet count (0.2 x 10(4)/microliters) was markedly decreased and megakaryocytes in the bone marrow were increased. By the treatment, platelet count recovered to 16.7 x 10(4)/microliters, while fibrin-degradation product levels were increased and hypofibrinogenemia developed, suggesting disseminated intravascular coagulopathy. Additional treatment with heparin was effective, and the coagulation studies became normal. In 1980, he again developed the episode with thrombocytopenia. At this time, prednisolone did not improve the episode, but heparin was effective. Since 1983, an enlargement of abdominal aorta had been recognized and gradually progressed. In 1983, he developed lumbago and abdominal pain, and received an emergency operation using artificial Y-graft vessel under the diagnosis of rupture of the aneurysm. There was no evidence of consumption coagulopathy at that time. He had been well until 1987, when he developed the third episode of thrombocytopenia with gingival bleeding. Thrombocytopenia was controlled with the treatment of heparin, but needed a continuous treatment with heparin. Thereafter, he has been well managed with self-injection of the anticoagulant, heparin sodium. PMID- 2593250 TI - [Initial symptoms of hematemesis from gastric varix with chromosomal abnormalities of t(2; 8) and 14q+ in a patient with acute lymphoblastic leukemia (FAB: L3)]. AB - A 71-year-old woman was hospitalized because of hematemesis on December 1, 1987. Her white blood cell (WBC) count was 41,200/microliters with 48% of lymphoblasts, and the bone marrow was hypercellular with more than 90% of blasts. The diagnosis of acute lymphoblastic leukemia (ALL) (FAB: L3) was made by morphologic, cytochemical and immunologic studies of the blasts. The examination of fiber gastroscope revealed remarkable varix in the stomach, suggesting portal hypertension accompanied by infiltration of leukemic cells into reticulo endothelial system. She died of respiratory failure because of bleeding into the trachea. The autopsy disclosed the massive infiltration of leukemic cells into the whole organs. In the chromosome study of the peripheral blood, t(2; 8) and 14q+ were observed, and these chromosomal abnormalities are relatively unusual in patients with Burkitt's lymphoma. PMID- 2593251 TI - [Prolymphocytic leukemia associated with serum hypo IgA]. AB - A 69-year-old man was admitted for the evaluation of leukocytosis with atypical cells. Physical examination revealed marked hepatosplenomegaly. The peripheral blood demonstrated Hb 10.1 g/dl, platelet 13.6 x 10(4)/microliters, and WBC 14200/microliters with 76% lymphoid cells. Bone marrow showed 52.4% lymphoid cells. These cells had a nucleus which was relatively large with a coarse chromatin structure and one prominent nucleolus. Under electron microscopy, these cells had a narrow cytoplasm containing a few mitochondria with some microvilli. The surface of these cells was positive for Ia, B1, B2, C3R, and had markedly elevated IgM-K and IgD-K surface immunoglobulins. Levels of IgG, IgA and IgM were 1140 mg/dl, 53 mg/dl, and 198 mg/dl respectively. He was diagnosed as having B PLL, and was treated with vincristine, cytarabine and prednisolone. Since B-CLL frequently in accompanied by reduced levels of one or several immunoglobulins, and the most significant is the decrease of IgA, it is speculated from our case that B-PLL is very similar to B-CLL in the abnormalities of B cell function. PMID- 2593252 TI - [Adult T-cell leukemia with massive melena due to marked gastrointestinal involvement]. AB - A 60-year-old man born in Okinawa was admitted to our hospital because of epigastralgia. Physical examination revealed general lymphadenopathy, mild hepatomegaly and skin eruption. The peripheral blood leukocyte count was 168,600/microliters, with 93% abnormal lymphocytes showing convoluted or lobulated nuclei. Anti HTLV-1 antibody was positive with titer of 1: 1280 (PA). Leukemic cells had typical ATL cells' surface markers (OKT3; 97.2%, T4; 93.3%, T8; 2.8%, OKIA1; 39.6%, IL-2R; 41.8%) and complete monoclonal HTLV-1 provirus DNA. Endoscopic examination with biopsy revealed massive involvement of ATL cells into gastric mucosa. In the course of the treatment, he had extremely massive melena, and was saved by emergency operation. Multiple ulcers were found in the resected colon. Histological examination showed the marked infiltration of the ATL cells into the mucous or submucous membrane. Thereafter, he was treated well with ALG (Anti Lymphocyte Globulin), until hypercalcemia occurred. He died of acute renal failure after hypercalcemia. PMID- 2593253 TI - [Appearance of Philadelphia chromosome at relapse of erythroleukemia in a 12-year old boy]. AB - A 12-year-old boy was referred to our hospital because of anemia and jaundice. On admission bone marrow smears were compatible with M6 classification of the FAB, revealing 74.5% erythroblasts of all nucleated cells and 40% blasts of nonerythroid cells. Karyotype analysis revealed 46, XY. Gene rearrangement within the breakpoint cluster region (bcr) on chromosome 22 was negative at this time. Complete remission was attained by a combination chemotherapy. However, at 10 months of remission, cytogenetic studies of the bone marrow demonstrated Ph1 positive (10%). One month later, the patient fully relapsed with a 75% Ph1 positive karyotype associated with positive bcr. Subsequently, the patient died of refractory leukemia. PMID- 2593254 TI - [Acute myelogenous leukemia developing in pregnancy with complete remission--a case report]. AB - A 27-year-old woman was admitted to our hospital complaining of purpuras and legs' edema in the 38th week of pregnancy. On admission, the hemoglobin was 7.8 g/dl, platelets 20,000/microliter and WBC 6,600/microliters with 52% blast cells. Bone marrow aspirate demonstrated 77.2% myeloblasts with prominent Auer rods, consistent with acute myelogenous leukemia. Receiving packed-red-cell and platelet transfusions, she delivered a normal male infant in the 39th week of pregnancy by normal labor. After delivery, she was placed on a combination chemotherapy of BHAC-MMP, subsequently DNR added. Four weeks later, a complete remission was obtained, lasting for almost one year, and her child has grown well without hematological disorder. Microscopic findings of the placenta obtained at delivery revealed no invasion of leukemic cells, but 9% blast cells were present in the placental cord blood. We reviewed 18 cases reported in Japan of acute leukemia in gestational period, that could obtain complete remission and keep the children growing well. Placental transmission of leukemic cells from mother to infant was discussed. PMID- 2593255 TI - [1 alpha(OH) D3 (Alfarol) is effective for the treatment of chronic B cell leukemia: a case report]. AB - We reported a case of chronic B-cell leukemia reacted to the administration of 1 alpha (OH)D3 (Alfarol-CHUGAI Pharm. Co.), The patient showed pancytopenia with IgM-kappa type monoclonal protein in the serum. The bone marrow aspiration was failed due to a dry tap, but the biopsied specimen showed a marked infiltration of small sized lymphoid cells with wide cytoplasm. The leukemic cells from peripheral blood showed a morphology of atypical hairy cells, Surface markers of the leukemic cells were IgM, D(kappa)+, CD 19+, CD 20+, CD 21- and HLADR+, The leukemic cells showed no L-tartrate resistant acid phosphatase sensitivity. This case was diagnosed as a chronic B-cell leukemia closely related to a hairy cell leukemia. The treatment with estrogen-chlorambucil compound (Bestrabucil-KUREHA Chem, Co.) or splenic irradiation was not effective. However, after two months' administration of Alfarol the regular blood transfusion was not needed because of increment of the Hb concentration. After eight months of its administration, the bone marrow aspirate showed a marked decrease in the number of the leukemic cells and a restoration of normal hematopoietic cells. This experience suggested that Alfarol in usefull for the treatment of chronic B cell leukemia including hairy cell leukemia and chronic lymphocytic leukemia. PMID- 2593256 TI - [Fulminant autoimmune hemolytic anemia with multiple organ failure]. AB - We report a rare case of fulminant autoimmune hemolytic anemia (AIHA) with multiple organ failure (MOF). A 40-year-old man was emergently admitted to our hospital because of conscious disturbance and jaundice. The peripheral blood revealed RBC 68 x 10(4)/microliter, Hb 3.5 g/dl, Ht 8.9%, Ret 30% (20,400/microliter), WBC 20,300/microliter, Plts 16.9 x 10(4)/microliter, indirect bilirubin 9.4 mg/dl. Both direct and indirect Coombs test were positive and the IgG autoantibody was identified. Bone marrow aspiration revealed hypercellularity with increased megakaryocytes and erythroid hyperplasia. The patient was diagnosed as having idiopathic warm type of AIHA and the therapy was started with prednisolone 80 mg/day from the first day of admission but hemolysis with reticulocytopenia was so rapidly progressive that he was in acutely life threatening state and MOF (acute renal failure, adult respiratory distress syndrome, congestive heart failure, liver dysfunction, rhabdomyolysis) appeared on the third hospital day. Plasma exchange therapy and hemodialysis were started and high dose methylprednisolone was given soon after rapid administration of sufficient blood transfusion. Dramatic improvement of hemolysis was noted and MOF was controlled after starting these therapies, but he died of exacerbation of MOF probably due to sepsis 40 days later. PMID- 2593257 TI - [Acute myelogenous leukemia with recurrence of the meningeal, spinal cord and the optic nerve infiltration with remission induction by Co therapy and maintained by intrathecal chemotherapy with Ommaya reservoir]. AB - A 42-year-old woman was diagnosed as having acute myelogenous leukemia (M 2 of FAB classification) in May, 1985. Complete remission was achieved with the BHAC DP therapy (BHAC, daunomycin and prednisolone). Whole skull irradiation and intra thecal chemotherapy were performed by way of prevention. In 1986, she developed her visual disturbance and paraplegia. Myelography and metrizamide CT indicate intraspinal and meningeal infiltration of leukemic cells in the upper thoracic spine. Leukemic cells were found in the cerebrospinal fluid but not in the bone marrow. Complete remission was obtained by irradiation and intrathecal chemotherapy. In Dec. 1986, Ommaya tubing was repeated. Hematological and neurological examinations showed no evidence of malignancy for 3 years. In Oct. 1988, she admitted to our hospital for the maintenance of the remission state, and died of sepsis. The result of autopsy revealed no leukemic cells in her CNS. It is said the intraspinal infiltration of leukemic cells is rather rare. As it is said the intrathecal injection of anti-leukemic agents is not effective for the intraspinal infiltration, irradiation should be needed. Therefore it is very important to critically differentiated intraspinal from meningeal infiltration. Furthermore, Ommaya tubing is effective in order to maintain remission in a patient with CNS leukemia. PMID- 2593258 TI - [Assay of blood coagulation factors in factor deficiency plasma]. PMID- 2593259 TI - [31st meeting of the Japan Society of Clinical Hematology. Nagoya, 9-11 November 1989. Abstracts]. PMID- 2593260 TI - [Progress in research on hypertension. Etiology, maintenance, physiopathology. drug therapy, complications]. PMID- 2593261 TI - [Simulation of cardiovascular control system and models of hypertension]. PMID- 2593262 TI - [Criteria for the diagnosis and evaluation of severity of hypertension]. PMID- 2593263 TI - [Role of the central nervous system and autonomic nervous system in the development of essential hypertension]. PMID- 2593264 TI - [Role of sodium and potassium in hypertension]. PMID- 2593265 TI - [Relationship of calcium, and magnesium with blood pressure]. PMID- 2593266 TI - [Role of vascular reactivity and neuronal factors in the development of hypertension]. PMID- 2593267 TI - [Role of the renin-angiotensin aldosterone system in the development of hypertension]. PMID- 2593269 TI - [The kallikrein-kinin system and blood pressure regulation]. PMID- 2593268 TI - [The role of catecholamines in hypertensive mechanisms of essential hypertension]. PMID- 2593270 TI - [Roles of prostaglandins and their related substances for the development of hypertension]. PMID- 2593271 TI - [Role of vasopressin in the development of hypertension]. PMID- 2593272 TI - [Role of an endogenous digitalis-like substance in the development of hypertension]. PMID- 2593273 TI - [Pathogenesis and treatment of renal hypertension]. PMID- 2593274 TI - [Pathogenesis and treatment of endocrine hypertension]. PMID- 2593276 TI - [Drug therapy of hypertension using diuretics]. PMID- 2593275 TI - [Pathogenesis and treatment of drug-induced hypertension]. PMID- 2593277 TI - [Clinical application of angiotensin converting enzyme inhibitors]. PMID- 2593278 TI - [Clinical application of calcium antagonists in the treatment of hypertension]. PMID- 2593279 TI - [Clinical application of serotonin antagonists in the treatment of hypertension]. PMID- 2593280 TI - [Planes in the treatment of hypertension]. PMID- 2593281 TI - [Prevention and countermeasures in disorders of cerebral circulation complicated by hypertension]. PMID- 2593282 TI - [Prevention and countermeasures in kidney diseases complicated by hypertension]. PMID- 2593283 TI - [Management of mild hypertension]. PMID- 2593284 TI - [Hypertensinogenic steroid]. PMID- 2593285 TI - [Development of animal models for hypertension research and current problems]. PMID- 2593286 TI - [Bone scintigraphy in evaluation of the effect of renal transplantation in patients with renal osteodystrophy]. AB - Bone scintigraphy before and after renal transplantation was studied in 14 patients with renal osteodystrophy. The radionuclide distribution patterns visualized on the images before transplantation were classified into two groups; one group with markedly increased tracer uptake throughout the whole skeleton, especially in the skull, another group with prominent tracer uptake in the soft tissues. These abnormal tracer accumulations improved after renal transplantation. Bone scintigraphy before and after renal transplantation provides useful information concerning the follow-up of patients with renal osteodystrophy. PMID- 2593287 TI - [Renography and renal imaging with 123I-orthoiodohippurate; comparison with 131I orthoiodohippurate]. AB - Renography and renal imaging with 123I-orthoiodohippurate (OIH) were performed in 29 patients with various renal diseases, and a comparison made with 131I-OIH. In all patients, renograms and images with 123I-OIH were superior to those with 131I OIH, because of the increased density and image excellence of 123I-OIH. In addition, dynamic images to evaluate renal blood flow, as well as high quality sequential excretion images, can be obtained with 123I-OIH. From our clinical results, 123I-OIH is expected to replace 131I-OIH in renal function studies. PMID- 2593288 TI - [CT of the pelvic kidney]. AB - Six cases of unilateral pelvic kidney are presented. CT features are summarized as follows: (1) an absence of a kidney in the renal fossa with normal sized opposite kidney: (2) a pelvic kidney whose hilus faces in various directions; and (3) homogeneous parenchymal enhancement and visualization of the pyelocalyceal system on post-contrast CT. In the study of suspected pelvic kidney, CT is a useful diagnostic tool. PMID- 2593289 TI - [Computed tomography of postoperative pelvic lymphocele]. AB - Computed tomography (CT) was obtained in seven patients with postoperative pelvic lymphocele. The CT appearance of the lymphocele was nodule or oval cystic mass of low attenuation. Most of lymphoceles located laterally in the external iliac region. They were identified on the first CT, mean 2.5 months after surgery. They became small (2 cases) or disappeared (4 cases, mean 7 months after surgery). Infection was noted in one case, and another patient had lower abdominal pain. One of different diagnoses is recurrence. PMID- 2593290 TI - [CT findings of pseudomyxoma peritonei]. AB - Four patients with pseudomyxoma peritonei were studied by computed tomography. CT images in all cases showed low density area simulating ascites in the peritoneal cavity. The low density area was due to gelatinous masses, which were proved by surgery or autopsy. The CT number of gelatinous masses was almost equal to that of water. Scalloping of liver and separated intestinal loops in the low density area were seen. One case had scattered calcifications in the low density area. The calcification in the low density area is a specific finding in pseudomyxoma peritonei. PMID- 2593291 TI - [Three cases of retroperitoneal cystic lymphangioma]. AB - Retroperitoneal cystic lymphangioma is a rare benign tumor. Three cases of retroperitoneal cystic lymphangioma with histological proof were reported. Every case revealed similar characteristic appearances on CT, such as 1. unilocular or multilocular cystic mass with homogeneous near-water density, 2. non-enhanced or slightly enhanced wall and septum, 3. commonly thin wall without irregularity, 4. compression of surrounding organs with sharp margin. No secondary changes such as hydronephrosis and ischemic change were noted in the surrounding compressed organs, revealing that this tumor is soft and the growth is slow. Several differential diagnoses were considered, but diagnosis was not so difficult on CT, considering anatomical relations and clinical appearances. PMID- 2593292 TI - [Is T2-weighted imaging reliable in the differential diagnosis of an adrenal mass? Dependence of signal intensity on the size of tumors]. AB - We reviewed T2-weighted images of 41 adrenal tumors. There were 25 adenomas and 16 non-adenomas. We compared the signal intensity of the adrenal tumors with that liver and classified the tumor/liver intensity ratio (TLR) into five categories; very low (much less than), low (less than), iso-intense (=), high (greater than), and very high (much greater than). The size of adenomas in diameter ranged between 8 mm-50 mm. TLR of 92% of adenomas less than 20 mm (13 cases) were (less than) or (=); when adenomas exceeded 20 mm (12 cases), 75% were (greater than) or (much greater than). TLR of non-adenomas all (greater than) or (much greater than). PMID- 2593293 TI - [MR imaging of gynecological neoplasms using a low-magnetic-field machine]. AB - Magnetic resonance (MR) images were obtained from 171 patients with benign and malignant neoplasms in the uterus and ovary, by using a low magnetic-field machine with 0.22 T, and its usefulness is discussed. Small uterine neoplasms (a few mm of its diameter) can be detected as an abnormal intensity. Therefore, the detectability is helpful for determination of their staging. In addition, some adenomyosis can also detected as distinctive findings, although it is difficult to point out those diseases by other imaging modalities. From MR images of ovarian cystic tumor, the biochemical information of its fluid content can be obtained. However, it is difficult to get distinctive features from MR images of solid neoplasms. Even though the magnetic field is low such as 0.22 T, MR images are useful for diagnosis of gynecological neoplasms because of the high contrast image quality and the capability of providing tomograms with arbitrary planes. PMID- 2593294 TI - [CT image of primary ovarian cancer seeding to the peritoneal cavity]. AB - Early diagnosis of primary ovarian cancer is difficult, because of a few symptoms and clinical signs, this cancer has many pathological findings and CT images. Therefore, initial CT Scan documents often the seeding to peritoneal cavity. We evaluated the seeding pathway to peritoneal cavity for 59 primary ovarian cancer by CT, especially ascites, omental metastasis, peritoneal metastasis and scalloping. PMID- 2593295 TI - [Carcinoma of the uterine cervix treated with TAO low-dose rate intracavitary radiation]. AB - Seventy-four patients with carcinoma of uterine cervix were treated radically with TAO low-dose rate afterloading system during 1972 to 1986. Relapse-free rates were 88.9% in stage I, 77.9% in stage II and 48.3% in stage III, and 5-year cause-specific survival rates were 88.9% in stage I, 77.2% in stage II, and 50.5% in stage III respectively. Late complication in recto-sigmoid region was noticed about 10%, but most of them in minor degree. The results remain satisfactory when compared with other published results. PMID- 2593296 TI - [A case of acute abdomen. Intestinal infarction due to superior mesenteric artery embolism]. PMID- 2593297 TI - [133Xe ventilation-perfusion scan of the lung in hypersensitivity pneumonitis]. PMID- 2593298 TI - [Diffuse abdominal uptake of 67Ga-citrate; report of three cases]. AB - Three cases, two peritoneal lymphomatosis and one tuberculous peritonitis, which showed diffuse abdominal uptake of 67Ga-citrate, were reported. 67Ga scan should be indicated for patients suspected of malignancy or inflammation with a lack of localized symptoms and signs in the abdomen. 67Ga-citrate scan also can give notable information on the evaluation of therapeutic response in those patients. PMID- 2593299 TI - [Angiomyolipoma of the kidney; report of two cases with a low fat component]. AB - We report two cases of unilateral renal angiomyolipoma. In both cases, our preoperative diagnosis was renal cell carcinoma because no low density area compatible with a fatty tissue was noted in the tumors. Histological examination revealed both tumors to be angiomyolipoma mainly composed of myomatous cells and immature fat cells. PMID- 2593300 TI - [Therapeutic embolization for bilateral renal angiomyolipomas with spontaneous rupture--a case report]. AB - A 64-year-old woman of bilateral renal angiomyolipomas with spontaneous rupture, not associated with tuberous sclerosis was reported. Superselective embolization for tumors using ethanol was successfully performed, preserving normal renal function. Transcatheter embolization was considered the treatment of first choice for the urgent circumstances with spontaneous rupture. PMID- 2593302 TI - [A case of retroperitoneal neurinoma]. AB - A case of retroperitoneal neurinoma is reported. The patient was a 34-year-old female without symptoms. CT scan showed a large low density mass, a part of which was enhanced. US showed a lobulated cystic mass. Angiography showed avascular mass and portal vein was shown with displacement and stenosis. Pathological diagnosis was benign retroperitoneal neurinoma (Antoni A and Antoni B). PMID- 2593301 TI - [A case of renal leiomyoma with remarkable calcification]. AB - A case of renal leiomyoma with remarkable calcification is reported. The patient is a 46-year-old female. The tumor is 9 x 10 x 12 cm in size and is occupied by granular minute calcifications. Angiographically segmental arteries are stretched by a tumor, in which there are minute tumor vessels and inhomogeneous tumor stain. PMID- 2593303 TI - [A case of myelolipoma originating from bilateral adrenal glands; a comparison of CT and pathological findings]. AB - We experienced a case of bilateral retroperitoneal tumor incidentally on CT which was carried out on suspicion of either cholelithiasis or choledocholithiasis. In company with other radiologic studies, US, angiography etc. we were able to make a correct diagnosis of adrenal myelolipoma preoperatively. Among these studies, CT coincided well with the structure of pathological findings and is thus the most powerful method for the diagnosis of myelolipoma. The case was discussed in addition to the studies of other literatures. PMID- 2593305 TI - [Percutaneous removal of a ureteral stent using a loop snare]. PMID- 2593304 TI - [A case of bilateral adrenal cortical carcinoma with special reference to image diagnosis]. AB - The patient, a 45-year-old male, complained of left flank pain and fever. CT revealed bilateral adrenal tumors, in which MRI disclosed inhomogeneous signal intensity with low signal intensity rim. Arteriography demonstrated bilateral adrenal tumors with moderately rich tumor vessels. PMID- 2593307 TI - [Effect of ursodeoxycholic acid on water immersion restraint stress ulcer of rats]. AB - Ursodeoxycholic acid (UDCA) has been used in the medical treatment of various gastrointestinal diseases. In this study, UDCA-supplemented rats were investigated to elucidate the role of UDCA in the pathogenesis of gastric mucosal lesions induced by water immersion restraint stress. In UDCA-administered rats, the increase of gastric mucosal lipid peroxide (LOP) and ulcer index after 2 hour's stress were prevented as compared with the rats fed on standard diet to serve as the control. In addition, the increase of serum and gastric mucosal catalase after the stress were also suppressed. These results suggested that antioxidant effect of UDCA on the lipid peroxidation may play a role in prevention of gastric lesions induced by water immersion restraint stress. PMID- 2593306 TI - [Studies on the damage of the cultured endothelial cells and K-562 cells by sclerosants (ethanolamine oleate, Aethoxysklerol and absolute ethanol) used in the treatment of esophageal varices]. AB - In injection sclerotherapy against esophageal varices, the damage of the endothelial cells of varices has been supposed to be most important for the formation of thrombi in the injected varices. Mechanisms of the destructive action of three sclerosants (ethanolamine oleate [EO], Aethoxysklerol [AS] & absolute ethanol [Et]) on endothelial cells of varices were studied by means of observation of morphological change of the cells and 51Cr release from the cells in a contact with these sclerosants using cultured human endothelial cells and culture cell line K-562 as target cells. Main mechanism for destructive action of EO on the endothelial cells was considered to be cytolysis through injury of cell membrane, since the cells disappeared immediately after addition of EO with marked release of 51Cr. The destructive action of AS on endothelial cells was considered to be mild cytolysis, since moderate destruction of the cells and moderate release of 51Cr were induced with AS. On the other hand, Et showed a fixative-destructive action on the cells without marked morphological change and with little release of 51Cr. Therefore, it was considered that EO and AS caused the damage of endothelial cells through their lytic action of the cell membrane, whereas Et caused it through the fixative action of the cell membrane. PMID- 2593308 TI - [The influence of theophylline on polyamine metabolism and colonic carcinogenesis induced by 1.2-dimethylhydrazine in mice]. AB - The administration of theophylline (120 mg/kg.day, 14 wk) to the drinking water of female BALB/c mice after treatment with 1,2-dimethylhydrazine (DMH) (30 mg/kg.sc, 1/wk, 14 wk) resulted in both an increase in number of colon carcinoma and increases in ornithine decarboxylase (ODC) activities and polyamine (PA) levels in colon tissue. This increase in number of colon carcinoma was about 3 fold to mice receiving same amount of DMH and drinking water without theophylline. ODC activities (pmoles 14CO2/hr/mg prot, mean +/- SD) in colon tissue were 122 +/- 10.6 (n = 6) in DMH with theophylline group, 28.3 +/- 2.13 (n = 8) in DMH alone group, 21.3 +/- 1.67 (n = 6) in control group respectively. Putrescine and spermidine levels (nmoles/g, mean +/- SD) were 31.0 +/- 10.5, 527 +/- 86.6 (n = 11) in DMH with theophylline group, 24.0 +/- 11.4, 464 +/- 129 (n = 11) in control group respectively. Thus with marked increase of ODC activities and slight increase of PA levels, theophylline has shown to significantly enhance the promoting phase of carcinogenic process with DMH. PMID- 2593309 TI - [Detection of gut hormone mRNAs by synthetic DNA probes in gut hormone producing tissues]. AB - Synthetic DNA probes were tested as hybridization probes for detecting gut hormone mRNAs. When 4 gut hormones, including gastrin, somatostatin, gastrin releasing peptide and calcitonin were examined, these probes were shown to be useful for mRNA detection in the tissues producing respective hormones. It was also revealed that there was a good correlation between the concentration of peptides determined by radioimmunoassay and the amounts of mRNAs. This methodology was applied for multiple gut hormone producing tumor with the aim to elucidate the mechanisms responsible for this phenomenon, and demonstrated that the tumor expressed a large amount of mature mRNAs encoding respective hormones. These results indicate that increase of mRNA production is one of the mechanism responsible for multiple gut hormones production by tumor. PMID- 2593310 TI - [Dissolution of cholesterol mixed stones with methyl tertiary butyl ether in vitro]. AB - Methyl tertiary butyl ether (MTBE) has been proposed as a new therapeutic material for the dissolution of pure cholesterol mixed stones. To determine the effect of solvent circulation and fragmentation on dissolution of cholesterol mixed stone in MTBE, we carried out in vitro experiments. The following results were obtained: 1) The addition of 1% EDTA and 0.5% UDCA in MTBE enhanced the dissolution of cholesterol mixed stones (56 +/- 8% of initial weight after 3 hours vs. 48 +/- 5% of initial weight after 3 hours in MTBE alone). 2) Cholesterol mixed stones with circulation of MTBE + 1% EDTA + 0.5% UDCA were dissolved more rapidly than those without. 3) Under in vitro condition, when cholesterol mixed stones were fragmented with URAT-1M stone disintegrator, fragments of stones were dissolved 96% of initial weight in solvent circulation of MTBE + 1% EDTA + 0.5% UDCA after 3-6 hours. In conclusion, these data indicated that both fragmentation of cholesterol mixed stones and solvent circulation of MTBE + 1% EDTA + 0.5% UDCA considerably accelerated dissolution of cholesterol mixed stones in vitro. PMID- 2593311 TI - [Clinical study on five cases of carcinoma of the papilla of Vater confined to the mucosa]. PMID- 2593312 TI - [Usefulness of continuous peritoneal dialysis (CPD) in the management of metabolic encephalopathy in adult type citrullinemia]. PMID- 2593313 TI - [The role leukotrienes and mast cells on acute gastric mucosal lesions]. PMID- 2593315 TI - [31st meeting of the Japan Geriatrics Society. 14-16 November 1989, Nagoya. Abstracts]. PMID- 2593314 TI - [A new experimental trial for dissolution of gallbladder stones]. PMID- 2593316 TI - [Two-color analysis of lymphocyte subpopulations in membranous nephropathy and minimal change nephrotic syndrome]. AB - Two-color flow cytometry was carried out to determine the correlation between cell mediated immunity and the development of the nephrotic stage in patients with membranous nephropathy (MN) and minimal change nephrotic syndrome (MCNS). In this study, lymphocyte subpopulations were measured by two-color flow cytometry using various monoclonal antibodies of the Leu series. Thirty patients with MN and 25 patients with MCNS were examined. Clinically, those patients were divided into four stages as follows: (1) untreated nephrotic stage, (2) prednisolone (PSL) treated nephrotic stage, (3) persistent proteinuria stage (incomplete remission, ICR), and (4) complete remission (CR). Pathologically, the patients with MN also divided into four stages I-IV, according to Churg's classification. The values of the Leu 3a/Leu 2a ratio in patients in the untreated nephrotic stage of MN and MCNS were significantly higher than those in the remission stage in both diseases (P less than 0.01, P less than 0.05, respectively). Two-color flow cytometry showed that the reduction of Leu2a positive cells was mainly due to a decrease of Leu 2a+15+ subsets (suppressor T cells) in the untreated nephrotic stage and relative increase of Leu 3a+8+ subsets (suppressor inducer T cells). There was no significant difference in these findings among the histopathological stages in patients with MN. Patients with MN and MCNS showed a significant elevation of Leu 2a+DR+ cells after the treatment of PSL. The abnormalities of suppressor T cells and suppressor inducer T cells in the peripheral blood appear to be correlated with clinical activities of the nephrotic syndrome due to MN or MCNS, but not to be related to the pathogenesis of either disease. It is postulated that PSL might stimulate Leu 2a positive cells and Leu 3a positive cells, and then increase the number of Leu 2a+15+ cells in the peripheral blood of patients with MN and MCNS. PMID- 2593317 TI - [Complement-mediated solubilization of immune complexes in immune complex nephritis]. AB - In order to examine the ability of complement to solubilize the immune complexes (IC) in vivo, we made acute or chronic serum sickness nephritis in 10 rabbits or 12 rats with injection of BSA as antigen (Ag). Animals were divided into two groups. The 500 mu or 50 mu/week of cobra venom factor (CVF) for rabbits or rats was administered intraperitoneally in one group of animals to reduce the serum complement levels and complement-mediated solubilization of immune complex. On the other hand, the 2 ml or 0.2 ml/week of turpentine oil (TO) was injected intramuscularly in another group of animals to elevate the serum complement levels. The renal biopsy was performed with weekly intervals in each animals, and the specimens were stained for antigen (BSA), antibody (IgG) and C3 by immunofluorescence techniques. The result in this experiments showed the significant difference between TO-, and CVF-treated animals in the degree of disappearance of IC in the kidney lesions. The undetectable amount of IC (especially BSA) was remained in the renal tissue of TO-treated animals. This fact indicated that complement might act to solubilize the IC deposited in the tissue in vivo also. PMID- 2593319 TI - [A study of microproteinuria in patients with collagen disease]. AB - To examine the subclinical renal damage in collagen disease, we analyzed the excretion pattern of microproteinuria. We studied 58 collagen disease patients including 25 RA (rheumatoid arthritis) patients, 15 SLE (systemic lupus erythematosus), 5 PSS (progressive systemic sclerosis), 4 MCTD (mixed connective tissue disease), and 9 others. Urinary protein was not detected by urine dipsticks in all patients. Urinary proteins, which were concentrated to 5 mg/ml, were subjected to linear gradient (4-30%) SDS-PAGE and then transferred to nitrocellulose membrane by electrophoretic blotting method. The membrane was stained with Auro Dye and the blotted proteins were identified by enzyme immunoassay using specific antibodies. The percentages of albumin of whole urinary proteins were 27.2 +/- 13.7% in RA and 25.8 +/- 12.6% in PSS, which were significantly lower than that of controls (42.1 +/- 15.3%). However no significant difference in the percentage of urinary albumin was noted between SLE and controls. The percentages of low molecular weight (MW) proteins (proteins having smaller MW than albumin) were higher in RA and PSS. Especially the bands with MW of 25,200 were prominent and these percentages were 11.3 +/- 6.1% in RA and 14.6 +/- 9.1% in PSS, which were significantly higher than controls (5.1 +/- 3.5%). These bands with MW of 25,200 were demonstrated to be free light chains of immunoglobulins by western blotting method. From the above observations, protein excretion patterns in RA or PSS patients were so-called tubular proteinuria, and especially free light chain excretion was increased. We proposed that tubular dysfunction and abnormal production of free light chain might exist frequently in collagen diseases, especially RA and PSS. PMID- 2593318 TI - [A study of microproteinuria in patients with diabetes mellitus]. AB - In order to investigate the early renal damage in diabetes mellitus, 89 diabetics without proteinuria by dipsticks and 67 normal control subjects were examined by means of SDS-PAGE. The relationships between electrophoretic patterns of urinary protein and duration of diabetes, age of patients, metabolic controls and stages of retinopathy were examined. 1) The percentage of higher molecular weight (MW) proteins (67,000 less than or equal to MW) was larger in diabetics than that in controls. Especially the percentage of proteins with MW between 67,000 and 94,000, which include transferrin was 13.9 +/- 6.9% in diabetics, significantly higher than that in controls (10.3 +/- 5.1%) (P less than 0.01). On the contrary, the percentage of low MW proteins (MW less than 67,000) was relatively small in diabetics. 2) The excretion of higher MW proteins increased until 16 years of diabetic duration, however that decreased after 16 years. Especially in the group with duration longer than 20 years, excretion of low MW proteins increased. 3) Electrophoretic patterns of urinary proteins in patients with good metabolic control were similar to those in normal controls. 4) Excretion of higher MW proteins increased in patients with retinopathic complication suggesting the progression to microangiopathy. From the above results, we concluded that increased excretion of higher MW proteins in diabetics may be the results of GBM damages in protein selectivity. In patients with longer history of diabetes, predominant excretion of urinary low MW proteins may be the result of tubular dysfunction due to macroangiopathy. PMID- 2593320 TI - [Methylguanidine synthesis by active oxygen generated by stimulated human neutrophils]. AB - In previous papers, we have reported that methylguanidine (MG), a known uremic toxin, was synthesized from creatinine (Cr) by active oxygen generated not only by chemical reagents but also by isolated rat hepatocytes. In this paper, we studied whether or not active oxygen generated by stimulated human neutrophils produces MG from Cr. MG was measured after incubating 2 x 10(6) human neutrophils for 2 h in 1 ml of Hanks' balanced salt solution (pH 7.4) containing 100 mg/dl Cr at 37 degrees C after the addition of phorbol myristate acetate (PMA). MG was measured by high pressure liquid chromatography followed by reaction with 9, 10 phenanthrenequinone. MG was synthesized by the stimulated neutrophils and not by the unstimulated ones. MG synthesis reached a plateau (1.11 +/- 0.03 nmol/120 min/2 x 10(6) cells) at a concentration of 0.125 microM PMA and reached a maximum value (1.95 +/- 0.03 nmol/120 min/2 x 10(6) cells) at a concentration of 100 mg/dl Cr. MG synthesis increased depending on the concentration of neutrophils between 1 and 8 x 10(6)/ml and increased depending on the duration of incubation up to 4 h. MG synthesis was strongly inhibited by superoxide dismutase, by the scavengers of hypochloride (taurine and methionine) and by sodium azide. Catalase and the scavenger of the hydroxyl radical (dimethyl sulfoxide) inhibited MG synthesis less effectively. The effects of the scavengers of active oxygen suggest the participation of active oxygen in MG synthesis from Cr in this system. Among the active oxygen species, superoxide anion and hypochloride play an important role in this system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593321 TI - [Renal failure in paroxysmal nocturnal hemoglobinuria]. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hemolytic disorder characterized by a membrane abnormality of red cells, and characterized by two major clinical features of gross hemoglobinuria and diffuse venous thrombosis. In Japan, the present report records the first case of acute renal failure complicating PNH with treated by hemodialysis and was almost completely reversible. CASE: A 41 year-old woman was admitted for high fever (39.8 degrees C), dyspnea and clinical signs of a respiratory infection. She was started on Cefotax 1,000 mg 3 times daily. She subsequently developed acute renal failure and which treated by hemodialysis and was almost completely reversible. Following treatment of her renal failure, respiratory infection and anemia, she initially made good progress and was discharged. PMID- 2593322 TI - [The mechanism responsible for the development of symptoms. 5. Anorexia]. PMID- 2593323 TI - [Case study: psychological approach in nursing. "Do I look like I have cancer?", negation by a patient who was informed of his condition]. PMID- 2593325 TI - [Introduction of team nursing: development of the system while valuing past experiences]. PMID- 2593324 TI - [Communication with patients: an encounter with a former patient and a memory of nursing interactions]. PMID- 2593326 TI - [4 key points in playing the role of team leader]. PMID- 2593327 TI - [Viewpoints of the leader in team nursing: in 6 directions]. PMID- 2593328 TI - [Communication technology for a successful leader in team nursing]. PMID- 2593329 TI - [Organization of work prepared by the team for the new team leader]. PMID- 2593330 TI - [Nurturing a new nursing leader: relationship with the pre-existing teams]. PMID- 2593331 TI - [Discussion on leaders in team nursing: young leaders' advice to new leaders]. PMID- 2593332 TI - [Sense of humor which changes nursing: a lecture by Ms. Jean P. Ruxton]. PMID- 2593333 TI - [Medical care in Finland]. PMID- 2593334 TI - [Bedside nursing. Nursing of a patient with lethal midline granuloma who accepted death without knowing the prognosis]. PMID- 2593335 TI - [Ms. Takako Watt and her experiences as a former cancer patient and a leader of a patients' organization. 14. 12 years after surgery]. PMID- 2593336 TI - [On King's "Nursing Theory" (3). The theory of achieving the goal]. PMID- 2593337 TI - [Nursing counseling. 2. A cancer patient and the question of telling him the result of diagnosis]. PMID- 2593338 TI - [Welfare and medical care in the aging society. 33. The home for the aged and the illusion of a family setting]. PMID- 2593339 TI - [International medical project in Colombia. 5. Hard working and socially respected Colombian nurses]. PMID- 2593340 TI - [Basic problems of patients undergoing radiotherapy. Nursing of patients undergoing radiotherapy--problems likely to develop and related to assistance]. PMID- 2593341 TI - [Nursing of patients undergoing radiotherapy. Acute reactions in patients undergoing radiotherapy and their management]. PMID- 2593342 TI - [Nursing of patients undergoing radiotherapy. Development of stomatitis due to radiotherapy: innovation in the diet designed for mouth ulcer]. PMID- 2593343 TI - [Nursing of patients undergoing radiotherapy. Special consideration toward visitors at the radiotherapy ward--with special reference to the prevention of infections]. PMID- 2593344 TI - [Nursing of patients undergoing radiotherapy. Investigation of the attitudes of patients undergoing radiotherapy--a study of 2 cases with the aid of PONR records]. PMID- 2593345 TI - [Nursing of patients undergoing radiotherapy. Nursing management of the rooms where sealed radioisotopes or unsealed radiation sources are used]. PMID- 2593346 TI - [A case study. Nursing of a patient undergoing radiotherapy for brain tumor--a patient suffering from insomnia and a loss of desire for recovery]. PMID- 2593347 TI - [A case study. Nursing of a patient receiving radiotherapy on the tongue--easing the pain and apprehension]. PMID- 2593348 TI - [A case study. Nursing of a patient undergoing radiotherapy for lung cancer]. PMID- 2593349 TI - [A case study. Nursing of a patient undergoing radiotherapy for breast cancer- interruption of the treatment due to acute adverse effects of radiotherapy]. PMID- 2593350 TI - [A case study of a patient undergoing radiotherapy of uterine cancer--an aged patient treated with RALS (remote after-loading system)]. PMID- 2593351 TI - [Nursing of a child undergoing radiotherapy of rhabdomyosarcoma]. PMID- 2593352 TI - [Progress in radiotherapy of cancer]. PMID- 2593353 TI - [Questions and answers in neurology. Pre- and post-operative care of a spoiled child with moya-moya disease and education of his mother]. PMID- 2593354 TI - [Questions and answers on respiratory diseases. Preoperative respiration training of a patient with compromised pulmonary function]. PMID- 2593356 TI - [Questions and answers on the care of patients with urologic diseases. Problems related to the catheters used with nephrostomy and their management]. PMID- 2593355 TI - [Questions and answers on circulatory diseases. Innovation in handling the ECG monitor]. PMID- 2593357 TI - [Questions and answers on the care of patients with motor system disorders. Itchiness suffered by patients with anterior spinal fusion and its management]. PMID- 2593358 TI - [Questions and answers on pediatric care. Sedation of infants during radiotherapy]. PMID- 2593359 TI - [Questions and answers on obstetrical care. Nursing of a puerperal patient readmitted with mastitis]. PMID- 2593360 TI - [Questions and answers on emergency care. Nursing of a patient complaining of itching of the head region during IABP (intra-arterial balloon pumping)]. PMID- 2593361 TI - [Questions and answers on psychiatric care. Response of the nursing personnel toward patients with delusions]. PMID- 2593362 TI - [Postoperative infections]. PMID- 2593363 TI - [Nursing of hypertensive patients]. PMID- 2593364 TI - [Reinforcement of psychological nursing--the use of psychology cards]. PMID- 2593365 TI - [Study on methods to ease the pain of patients who are required to have absolute rest following heart catheterization--based on the review of the nursing records of 60 clinical cases]. PMID- 2593366 TI - [Nursing research on self-care of diabetic patients. 5. Diabetic patients' knowledge of diet therapy and their ego state]. PMID- 2593367 TI - [Theory and practice in family therapy. Commentary: the theory and practice in family treatment from the viewpoint of systems approach]. PMID- 2593368 TI - [Theory and practice in family therapy. Commentary: brief therapy--solution focused approach]. PMID- 2593369 TI - [Theory and practice in family therapy. Commentary: family therapy from the viewpoint of communication]. PMID- 2593370 TI - [Theory and practice in family therapy. Commentary: Bowen's family systems theory and family support]. PMID- 2593371 TI - [Orem's model used for health promotion: directions from research]. PMID- 2593372 TI - [The approach to the English monograph. To challenge your translation, to discover your mistakes (2)]. PMID- 2593373 TI - The proceedings of the 66th annual meeting, the Physiological Society of Japan. April 5-7, 1989 (Okayama). Abstracts. PMID- 2593374 TI - The effect of prophylactic anti-asthma drugs on PAF-induced platelet accumulation in the thorax of the guinea pig. AB - Intravenous infusion of platelet activating factor (PAF) causes an accumulation of platelets within the thorax of the guinea pig that is accompanied by increased sensitivity of the airways to spasmogens. A crystal scintillation detector has been used for measurement of intrathoracic accumulation of 111Indium-labeled platelets during responses to PAF. PAF-antagonists inhibit development of airway hyperreactivity, do not diminish platelet accumulation in response to an intravenous infusion of PAF. It is therefore concluded that intrathoracic platelet accumulation per se is not the determinant of increased airway reactivity. PMID- 2593375 TI - Inhibition of PAF-induced eosinophil accumulation in pulmonary airways of guinea pigs by anti-asthma drugs. AB - Intraperitoneal (i.p.) injection of platelet activating factor (PAF) in guinea pigs caused a dose-related increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). The prevalence of eosinophils in BALF had significantly increased within 1 hr of i.p. injection of PAF (10 micrograms/animal) and was maximal after 24 hr. Subcutaneous osmotic mini-pumps were used to administer drugs for 5 days prior to i.p. injection of PAF (10 micrograms/animal) and for the subsequent 24 hr. The percentage increase of eosinophils in BALF, due to PAF, was inhibited in animals treated with dexamethasone, aminophylline, cromoglycate, tranilast or ketotifen, but not in animals treated with oxatomide, azelastine, amlexanox, ibudilast or AA-861. These results suggest that inhibition of pulmonary eosinophilia may be a necessary property of prophylactic anti-asthma drugs and provide indirect evidence favoring a role for PAF in eosinophilia of asthma. PMID- 2593376 TI - Changes in glutathione peroxidase system and pyridine nucleotide phosphate levels in kidneys of cephaloridine-administered rats. AB - To elucidate the nephrotoxic mechanisms of cephaloridine (CER), changes in renal contents of glutathione (GSH), glutathione disulfide (GSSG), reduced and oxidized nicotinamide adenine dinucleotide phosphates (NADPH and NADP) and changes in renal activities of glutathione peroxidase, glutathione reductase and glucose-6 phosphate dehydrogenase were examined for 15 days in rats that received single intravenous injections of CER in doses of 0 (control), 100 and 1,000 mg/kg body weight. Significantly different changes from the control group were observed in the 1,000 mg/kg group. The 1,000 mg/kg group showed elevations in renal NADP and NADPH contents and decrements in renal GSH content in the period of the 1st to 3rd hour after the CER-administration. Thus, the fall in renal GSH content was considered to be a cause for renal injury due to the oxygen radicals observed in the early period. After the 6th hour, the 1,000 mg/kg group showed decreases of renal glutathione peroxidase and glutathione reductase activities and increases of renal glucose-6-phosphate dehydrogenase activity as well as GSH content. Although accumulation of GSH in the kidney was clearly observed in the late period, the more highly aggravated renal injury was speculated to be due to the decreased level in the utilization of GSH according to the fall of renal glutathione peroxidase activity. PMID- 2593377 TI - Pretreatment with a single bolus injection of polyoxyethylene-modified superoxide dismutase prevents reperfusion induced arrhythmias in the anesthetized rat. AB - Effects of a newly introduced polyoxyethylene-modified superoxide dismutase (SOD POE) on reperfusion induced arrhythmias were examined in the pentobarbital anesthetized rat. Reperfusion induced arrhythmias were elicited by occlusion of the left anterior descending coronary artery (LAD) for 15 min and subsequent release. The LAD occlusion was performed by compressing the artery using a suction cup of 2 mm in diameter placed on the LAD to which negative pressure was applied. The LAD occlusion and release was repeated at an interval of 30 min. SOD POE or human SOD (h-SOD) (1000 U/kg) was injected intravenously 15 min prior to the occlusion at the second trial of the occlusion. In the control group, various types of arrhythmias including ventricular fibrillation (Vf), ventricular tachycardia (VT), premature ventricular contraction (PVC) and premature atrial contraction (PAC) were elicited immediately after release of the occlusion. In the SOD-POE-treated group, Vf and VT were completely prevented and the numbers of PVC and PAC significantly decreased, while pretreatment with h-SOD did not prevent the occurrence of reperfusion induced arrhythmias. The protective effects of SOD-POE lasted for more than 90-120 min. The plasma half life for SOD-POE was 10.8 hr, while that for h-SOD was 8.6 min. Results indicate that intravenous administration of SOD-POE would provide a new means of preventing reperfusion induced arrhythmias occurring in clinical situations. PMID- 2593378 TI - Effects of bifemelane hydrochloride on various cholinergic markers in cortical and subcortical regions of aged rats. AB - The effects of bifemelane hydrochloride (BF) upon various cholinergic markers, muscarinic receptors, acetylcholinesterase (AChE) and choline acetyltransferase (CAT), in the aged rat brain were examined. Marked reduction of the density of muscarinic receptors (Bmax) as well as AChE and CAT activity concomitant with aging was observed. Administration of BF in daily doses of 10 mg/kg for 4 weeks to aged rats significantly decreased the apparent dissociation constant (Kd) for QNB in muscarinic receptors in the forebrain, but did not affect the value of Bmax. CAT activity also increased significantly compared with that of control aged rats, but administration of BF did not alter AChE activity. These results indicate that long-term treatment with BF enhances the affinity of muscarinic receptors for QNB as well as CAT activity and that BF may have therapeutic application in the treatment of CNS cholinergic dysfunctions. PMID- 2593379 TI - A new antitumor antibiotic, FK973: its metabolism in the blood and the antitumor effects of its metabolites on experimental models. AB - Our previous studies showed that a new, substituted dihydrobenzoxazine, FK973 (11 acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1,11-diazatetracyclo+ ++- [7.4.1.0(2,7).0(10,12)tetradeca-2,4,6-trien-6,9-diyl diacetate), which is a triacetylated derivative of the fermentation product FR900482 of Streptomyces sandaensis No. 6897, had potent antitumor effects on experimental tumors in vivo and in vitro. In the present study, we investigated the metabolism of FK973 in the blood of human and animals and the antitumor effects of its metabolites. After the incubation of FK973 in the blood (hemolysate) or serum of humans, dogs, rats and mice, it was rapidly metabolized to two diacetates and a monoacetate, and slowly to FR900482. FK973 and all its deacetylated metabolites showed strong cytotoxicity on in vitro cultured murine L1210 leukemia cells, and the cytotoxicity of FK973 was the most potent. In the vivo experiments, FK973 and its metabolites prolonged the life of mice bearing ascitic P388 leukemia, and it potently inhibited the growth of murine B16 melanoma and Colon 38 adenocarcinoma implanted subcutaneously in mice. FK973 was the most effective compound. Thus, these results suggest that the antitumor effects of FK973 are stronger than those of its deacetylated metabolites produced in the blood of humans and animals. PMID- 2593380 TI - Effects of S-312, a new calcium antagonist, on the mechanical and electrophysiological responses of isolated cardiovascular preparations. AB - S-312, a new calcium antagonist with a bicyclic dihydrothienopyridine structure, potently relaxed the helical strips of various isolated rabbit arteries precontracted with high K+-depolarization, serotonin (5-HT) and U46619 (thromboxane A2 analogue), and it competitively inhibited Ca++-induced contractions in depolarized basilar and femoral arteries. These effects of S-312 were more potent than nifedipine and almost comparable to or slightly more potent than those of nicardipine. In comparison with nifedipine and nicardipine, the calcium antagonistic effect and the relaxant effect on 5-HT-induced contractions of S-312 were most prominent in the basilar artery. The potent vasodilating action of S-312 in the high K+-depolarized basilar artery was not easily reversed by washing. S-312 did not affect Ca++-induced contraction in the skinned fiber of guinea pig taenia caecum. The negative inotropic effect of S-312 in isolated guinea pig left atria was much less potent than those of nifedipine and nicardipine. S-312 above 10(-7) M preferentially increased AV nodal conduction time in Langendorff-perfused isolated rabbit hearts; and above 3 x 10(-8) M, it mainly decreased the maximum upstroke velocity of the action potential in isolated rabbit sinus node preparations. In summary, the present results indicate that S-312 is a potent new calcium antagonist possessing vasculoselectivity, especially for cerebral vessels. PMID- 2593381 TI - Chronotropic and inotropic effects of kampo extracts in the canine isolated, blood-perfused heart preparations. AB - Cardiac effects of drugs used for circulatory disorders in traditional Japanese medicine based on ancient Chinese medicine (Kampo Medicine): Saikoka-ryukotsu borei-to, Oren-gedoku-to, Toki-shakuyaku-san, Shimbu-to, Moku-boi-to, Ryo-kei jutsu-kan-to, Sha-kanzo-to, Keishi-ninjin-to, Toki-to and Ryo-kan-kyo-mi-shin-ge nin-to were investigated using canine isolated, blood-perfused sinoatrial node and papillary muscle preparations. Single injections of small doses of Oren gedoku-to, Moku-boi-to and Ryo-kan-kyo-mi-shin-ge-nin-to (0.1 to 3 mg) dose dependently increased the sinoatrial rate and the developed tension of papillary muscle, while other drugs showed almost no effect on these parameters. All the drugs had almost no effect on the blood flow through the nutrient arteries of each preparation. The positive chronotropic and inotropic effects induced by Oren gedoku-to, Moku-boi-to and Ryo-kan-kyo-mi-shin-ge-nin-to did not show tachyphylaxis and were not affected after pharmacological denervation by tetrodotoxin treatment or by reserpine pretreatment, but were significantly suppressed by atenolol. These results indicate that these three drugs act as beta adrenoceptor agonists to produce clinically useful cardiac effects. PMID- 2593382 TI - Quantitative autoradiographic localization of the M1 and M2 subtypes of muscarinic acetylcholine receptors in the monkey brain. AB - The distribution of muscarinic acetylcholine receptors (mAChR) was investigated in the monkey brain by means of quantitative in vitro autoradiography. 3H-QNB, 3H pirenzepine (PZ) and 3H-AF-DX 116 were used for labelling total mAChR, M1 and M2 receptors, respectively. 3H-PZ and 3H-AF-DX 116 showed specificity to each receptor subtype in the monkey brain. On sections containing the putamen and globus pallidus, the sum of Bmax values of 3H-PZ and 3H-AF-DX 116 binding sites was almost close to that of 3H-QNB binding sites. Autoradiographic distributions of muscarinic subtype receptors in the monkey brain were similar to those reported in the rat brain; that is, M1 receptors were dominant in most areas of the telencephalon, while M2 receptors were richly distributed in the brainstem and cerebellum. However, some nuclei of the brainstem such as the central gray matter, superior colliculus, substantia nigra, nucleus of the oculomotor nerve, pontine nucleus and inferior olivary nucleus, had relatively high ratios of M1 receptors in the monkey brain. In addition, the cortical lamminar distribution of M2 receptors noticed in the rat was not observed in the monkey brain. Knowledge about the localizations of M1 and M2 receptors in various brain regions in the monkey brain will increase our understanding of the functions of the brain cholinergic system in the primate. PMID- 2593383 TI - Effects of CV-4093, a new dihydropyridine calcium channel blocker, on renal hemodynamics and function in stroke-prone spontaneously hypertensive rats (SHRSP). AB - Renal effects of CV-4093, a newly developed dihydropyridine calcium channel blocker, were examined using anesthetized stroke-prone spontaneously hypertensive rats, and the findings were compared with those of nicardipine. An intravenous injection of CV-4093 (2 micrograms/kg) produced long-lasting hypotension with a slow-onset accompanied by moderate renal vasodilation. There were no appreciable alterations in glomerular filtration rate (GFR) and urine formation, except that urine flow (UF) increased significantly during the first 10 min after injection. When CV-4093 was administered at 10 micrograms/kg, the hypotensive action was markedly augmented. Eighty minutes after the injection, a decrease in mean arterial pressure of about 45 mmHg was observed. Simultaneously, renal blood flow increased significantly from the control value of 5.76 +/- 0.46 ml/g.min to 6.94 +/- 0.28 ml/g.min. Renal vascular resistance decreased immediately after the injection, and the response lasted for over 3 hr, thereby indicating the marked and sustained renal vasodilating effect of CV-4093. GFR was constant throughout the experiment, but UF and urinary excretion of sodium were increased significantly. Fractional excretion of sodium was also elevated, thereby suggesting an inhibitory action of CV-4093 on renal tubular reabsorption of sodium. Nicardipine at a dose of 10 micrograms/kg, a dose producing an effective hypotensive action, caused no significant increases in RBF and urine formation. The renal vasodilating and diuretic actions of CV-4093 may provide a beneficial effect in the treatment of hypertension. PMID- 2593384 TI - Carbon monoxide (CO)-induced hypoxia in mice: evaluation as an experimental model of cerebral ischemia for drug screening. AB - An injection of 12.5 ml of carbon monoxide (CO) gas into an air-filled chamber (780 ml in volume) caused the death of the ICR or ddY mouse (6-8 weeks old) inside. The average survival time was 2.5 min for either sex of animals treated with nothing or saline and never exceeded 8 min. Pretreatment with pentobarbital Na (30 mg/kg, i.p.), hopantenate Ca (100 mg/kg, i.p.), vinpocetine (5 mg/kg, i.p. or 50 mg/kg, p.o.), flunarizine HCl (5 mg/kg, i.p.), glucose (6 g/kg, i.p.), phenobarbital (30 mg/kg, i.p.), phenytoin (20 mg/kg, i.p.), arginine HCl (100 mg/kg, i.p. or 1 g/kg, p.o.) and alanine (100 mg/kg, i.p. or 1 g/kg, p.o.) prolonged the survival time of male mice. Insofar as tested, female mice responded rather poorly to these pretreatments. Survival for longer than 8 min occurred in some of the drug-pretreated animals of either sex. To be noted is the finding that most of the animals which survived 8 min once were able to survive the second 8 min on the following day without any drug-treatment. Monitoring of the time course of carboxyhemoglobin formation revealed that the carboxyhemoglobin level reached a plateau of 70% saturation within 2 min and then gradually increased. The lethal level was about 72%. Pentobarbital decreased the formation rate but did not elevate the lethal level. The results indicate that the CO-induced hypoxia model of mice is usable for screening of drug candidates which may be effective for treatment of human ischemic diseases. PMID- 2593385 TI - Histamine-induced villous damage in the rat duodenum. AB - A single s.c. administration of histamine dose-dependently (5-20 mg/kg) induced villous damage of the proximal duodenum in 24-hr fasting rats. Time course studies indicate that histamine (20 mg/kg) induced severe exfoliation of the epithelial cells at the villous tips of the duodenal mucosa 0.5 hr after administration. The damage, however, tended to heal with time, and recovery was nearly complete 8 hr later. This villous damage was significantly inhibited by pretreatment with sodium bicarbonate given orally or cimetidine, omeprazole and NC-1300 given subcutaneously. Histamine (20 mg/kg) significantly stimulated gastric acid secretion and lowered the intraduodenal pH for 1 hr. Gastric content was significantly greater than that in the control group for 1 hr after histamine administration, probably due to stimulated gastric secretion and delayed emptying. We conclude that a single administration of histamine induces microscopical duodenal damage by stimulation of gastric acid secretion, but the damage heals with time, probably as a result of the short periods of acid stimulation and delayed emptying. PMID- 2593386 TI - Natriuretic action of manidipine hydrochloride, a new calcium channel blocker, in spontaneously hypertensive rats. AB - Effects of manidipine, a new dihydropyridine derivative, on sodium and water excretion were examined in conscious spontaneously hypertensive rats. Manidipine (3 mg/kg) significantly increased the sodium and water excretion in the urine collected for 3 hr after the calcium antagonist was orally administered, and its natriuretic action was more prominent than those of nifedipine and nicardipine (3 mg/kg). These results suggest that manidipine may be useful for treating hypertension. PMID- 2593387 TI - The spread and prognosis of carcinoma in the region of the pancreatic head. AB - Tumor infiltration and prognosis were studied in 73 patients who underwent surgery for carcinoma in the region of the pancreatic head, in order to evaluate the grade of malignancy of pancreatic cancer. Twenty three patients had carcinoma of the head of the pancreas, 16 had carcinoma of the intrapancreatic bile duct and 34 had carcinoma of the papilla of Vater. It was found that the prognosis in carcinoma of the head of the pancreas was not related to tumor size, but to lymph node metastasis and the pancreatic capsular or perineural invasion of the tumor. The poorer prognosis seen in carcinoma of the head of the pancreas could be attributed to the fact that lymph node metastasis and invasion of the pancreatic capsule or nerve plexus occurred much more frequently in this carcinoma than in carcinoma of the other two areas. The 5-year survival rate of the patients with carcinoma of the head of the pancreas was 12.5 per cent, this being significantly lower than that of the patients with either carcinoma of the papilla of Vater (50.0 per cent) or carcinoma of the intrapancreatic bile duct (44.4 per cent). These findings suggest that lymph node metastasis and pancreatic capsular or perineural invasion closely correlate with the prognosis of patients with pancreatic carcinoma. PMID- 2593388 TI - Hydrochloric acid for treating metabolic alkalosis. AB - Six patients with severe metabolic alkalosis were treated with intravenous hydrochloric acid (HCl) infusion. HCl was given through a central venous catheter, at a concentration of 0.1 mEq per ml. At least two of the following criteria were considered for initiation of the therapy: An arterial pH of greater than 7.45, a base excess (BE) of greater than +7 mmol/L, a PaCO2 of greater than 50 mmHg. The HCl amount was calculated using the BE formula, however, two thirds was infused for avoiding excessive acid loading. Patients were monitored by the blood gases, serum electrolytes, hemoglobin, hematocrit, bilirubin determinations and blood smear findings. While a significant decrease was noticed in pH and BE values, moderate changes were detected in PaCO2 due to different ventilatory status of the cases. All laboratory test results remained within normal limits and no complication was encountered. The advantage of the therapy is that less volume is needed for the correction of alkalosis, particularly in the cases requiring fluid restriction. HCl therapy, moreover, is a safe and time-saving method because of having rapid response to the treatment in the critically ill surgical patients. PMID- 2593389 TI - Radiation and surgical stress induce a significant impairment in cellular immunity in patients with esophageal cancer. AB - The effects of preoperative radiation plus surgical stress on immunity were examined in 29 patients with esophageal cancer, including 14 patients who experienced radiation therapy and 15 who did not, as well as 15 age-, sex- and body weight-matched control subjects. Absolute numbers of the total lymphocytes and OKT3 (all T cells), OKT4 (helper/inducer T cells) and OKT8 (suppressor/cytotoxic T cells) positive lymphocytes were almost the same in both patient groups before treatment. Both the in vitro response to phytohemagglutinin (PHA) and antibody dependent cell-mediated cytotoxicity (ADCC) were depressed in the patients when compared to the controls before treatment. Dual treatment of radiation and surgery led to a marked reduction of lymphocytes in the numbers and activities of PHA and ADCC, when compared to findings in the non-radiation group. Especially, the number of OKT4 positive lymphocytes and the OKT4 to OKT8 ratio decreased most and recovery was slow. While ADCC activity in the non-radiation group recovered at 28 postoperative days (POD), the response to PHA did not return to the pretreatment levels. Serum levels of IgG, IgM and IgA were within normal limits throughout the course of treatment. The B1 (all B cells) positive lymphocytes significantly decreased after the treatments. These results suggest that radiation plus surgery shifts the host immunity toward immunosuppression and induces a significant impairment of cellular immunity in patients with esophageal cancer. PMID- 2593390 TI - The policy of surgery for small carcinoid tumors of the rectum. AB - In this report, we discuss the current policy of surgery for small carcinoid tumors of the rectum, with reference to our own cases and also to those reported in the literature. Ten cases of rectal carcinoid tumors were surgically treated at the National Kyushu Cancer Center over a period of sixteen years and three months. The tumors ranged in size from 0.2 to 1.0 cm, with an average of 0.5 cm, and all were confined to the submucosa. The lesions were treated by local excision in eight patients and by low anterior resection in the other two cases, where transanal or transsacral excision was considered difficult. No lymph node involvement was found in these two cases. All patients are alive and well without recurrence, after an average follow-up time of three years and six months. According to the literature, the incidence of metastasis from rectal carcinoid tumors smaller than 1 cm is very low, ranging between 1.7 to 3.4 per cent, and it therefore seems that most such lesions can be treated by local excision alone. If, however, any muscle invasion or lymphatic vessel invasion is demonstrated, then radical surgery is recommended. PMID- 2593391 TI - Myocardial protection by a left ventricular assist device during reperfusion following acute coronary occlusion. AB - To evaluate the effects of a left ventricular assist device (LVAD) during the reperfusion period following acute coronary occlusion, sixteen mongrel dog hearts were subjected to 1 hour's occlusion of the circumflex coronary artery and then reperfused for 6 hours. In seven control dogs (control group), the hearts were reperfused without any support. In nine LVAD dogs (LVAD group), however, the left ventricles were supported by the application of a pneumatic driven diaphragm-type pump for 5 hours and then reperfused for another hour without any device. Triphenyltetrazolium chloride was used to determine the extent of infarction. The results showed a significant reduction in the area of infarct (AI) as a percentage of the area at risk (AR) in the LVAD group compared with the control group, the AI/AR being 22.3 per cent for the control group versus 4.8 per cent for the LVAD group (p less than 0.05). The cardiac output was also significantly higher in the LVAD group compared with the control group. The per cent systolic shortening in the ischemic region of the LVAD group showed a significantly better recovery, being 75.8 per cent for the LVAD group versus 24.4 per cent for the control group (p less than 0.01). It was concluded that the application of a LVAD during reperfusion after 1 hour's coronary occlusion results in a significant reduction of infarct size and provides improvement in both regional and global cardiac function. PMID- 2593392 TI - Resection of carcinoma in the cervical esophagus following prior removal of a thoracic esophageal carcinoma--a case report. AB - We report herein, a rare case of a patient who, having undergone resection of a thoracic esophageal cancer, underwent removal of a cervical esophageal cancer, for which a free jejunal graft with microvascular anastomoses was utilized. The tumor in the cervical esophagus had originated from a second primary squamous cell cancer, which had occurred synchronously but had unfortunately escaped detection before the first operation. Due to the high incidence of other multicentric neoplasma or metastatic skip lesions accompanying esophageal carcinoma, careful evaluation during preoperative examinations in order to avoid overlooking another lesion, especially in the cervical portion of the esophagus is imperative. PMID- 2593393 TI - Adenofibromyomatous hyperplasia of the extrahepatic bile duct--a report of two cases. AB - Two patients with adenofibromyomatous hyperplasia located at the distal end of the extrahepatic bile duct are reported herein. The chief symptom in both patients was upper abdominal pain and the lesions found involved the proliferation of submucosal mucous glands and fibrous elements. Further progress in imaging diagnostic techniques would increase the frequency with which such lesions are discovered. But, even now, if mural irregularities and shadow defects are found in the extrahepatic bile duct, particularly in the distal end of the common bile duct, the possibility of a benign lesion such as adenofibromyomatous hyperplasia should be taken into consideration when making a diagnosis. PMID- 2593394 TI - Carcinoma arising in fibroadenoma of the breast--a case report and review of the literature. AB - A 47 year old woman with two isolated lumps in her right breast underwent an excisional biopsy and the histological findings of both lesions revealed fibroadenoma with an in situ lobular carcinoma. Patey's modified radical mastectomy was performed after which careful follow-up was continued. To date, a total 161 cases of carcinoma arising in a fibroadenoma have been reported in the world literature and a review of these literature is given following the case report. PMID- 2593395 TI - Popliteal artery entrapment syndrome of the monozygotic twin--a case report and pathogenetic hypothesis. AB - A 22 year old Japanese man with popliteal artery entrapment syndrome in which both popliteal arteries were segmentally occluded and deviated medially, underwent surgical treatment by grafting and patching with autologous veins. His identical co-twin was also found to have a less severe form of popliteal artery entrapment syndrome. This is the first report of popliteal artery entrapment syndrome presenting in a pair of monozygotic twins and the concordance of the syndrome suggests that genetic factors may play a part in the development of this rare syndrome. PMID- 2593396 TI - The general rules for clinical and pathological recording of breast cancer. Japanese Breast Cancer Society. PMID- 2593397 TI - [The surgical treatment of ruptured thoracic aortic aneurysm with use of permanent bypass]. AB - Two surgical cases with ruptured thoracic aortic aneurysm were reviewed. Case 1 was a 74-year-old female, and Case 2 was a 77-year-old female. In both cases, chest X-ray examination revealed a mass like shadow in the left superior mediastinum, and aortography demonstrated a ruptured saccular aneurysm distal to the left subclavian artery. Midsternotomy and an incision over the third left intercostal space were made to approach the aneurysm. Since inflammatory adhesion was marked in the perianeurysmal area, a permanent bypass was placed between the ascending and descending aorta followed by exclusion of the aneurysm. One of the two cases was alive, but the other case was died due to bleeding from the area of permanent aortic clamp. PMID- 2593398 TI - [PTCA and coronary artery bypass operation prior to subsequent surgery of gastric cancer in patients with coronary artery disease]. AB - Two patients with coronary artery disease required operation for gastric cancer. In one patient with single vessel disease, 37 days later after successful PTCA, gastric resection for early gastric cancer was performed without any cardiac complication. The other patient with severe three vessel disease initially underwent coronary artery bypass operation, and 13 days later gastric resection for advanced cancer was performed. This patient developed supraventricular arrhythmia as a sole complication which was easily controlled by medical treatment. In both cases, fentanyl was used as an anesthetic agent and nitroglycerin was continuously administered intravenously during the perioperative period. ECG, central venous pressure, and direct arterial pressure were also carefully monitored. We feel that noncardiac operation such as gastric resection can be performed without major cardiac complications even shortly after coronary artery bypass operation. PMID- 2593399 TI - [Effectiveness of the bidirectional Glenn shunt for the univentricular heart]. AB - Two cases underwent a modified Fontan operation with simultaneous superior vena cava-right pulmonary artery end-to-side anastomosis, which we called "bidirectional Glenn shunt". This anastomosis seems to be so effective for reduction of right arterial volume loading, and could proved life-saving in the case with the acute obstruction at the site of the right atriopulmonary artery anastomosis immediately after surgery. PMID- 2593400 TI - [Clinical evaluation of perioperative myocardial infarction as a complication of valve replacement]. AB - Perioperative myocardial infarction (PMI) is a well-known complication of coronary artery surgery, but rarely encountered in valvular surgery. We have experienced 6 cases of valve replacement with PMI, using blood cardioplegia since 1979. Those patients (5 men, one woman; mean age 47 +/- 8 years) had no previous angina, and preoperative CAG revealed no significant stenosis. Three patients were reoperative cases. A diagnosis of PMI was established by the following criteria; an abnormal increase in maxCPK-MB (greater than 150 IU/l), new Q waves at ECG, positive 99mTc-PYP scan (grade 3-4). The area of PMI was inferior in 4 patients, posterior in one, and anterior infarction was seen in only one case. Three cases required IABP, but all 6 cases showed good exercise capacity by Treadmill exercise test in late stage. Several factors are thought to be the cause of PMI at valvular surgery; such as coronary air embolism, perioperative coronary spasm, inappropriate topical hypothermia, etc. Prognosis is not necessarily poor, however much attention should be paid to prevent PMI in valve replacement. PMID- 2593401 TI - [A case of congenital absence of the right coronary aortic cusp]. AB - A 12-year-old boy with absence of the right coronary cusp underwent aortic valve replacement with a 21 mm St. Jude Medical prosthetic valve. He was known to have noncyanotic congenital heart disease at the age of 2 months. The diagnosis of aortic insufficiency was first made when he was 1 1/4 years old. Intensive medical treatment was continued while he was growing up. Cardiac catheterization was performed repeatedly at ages 3 1/2 and 7. The findings on the fourth cardiac catheterization at 12 years of age were pulmonary arterial pressure of 90/60 mmHg, left ventricular end-diastolic pressure of 25 mmHg and poor contraction of the left ventricle. Although IABP support was necessary for treatment of severe low cardiac output state in the early postoperative period, he was discharged at 1 month after operation, Now, he goes to school under anticoagulant therapy. Intensive medical care followed by elective aortic valve replacement may be a useful treatment for isolated congenital absence of the aortic valve cusp. PMID- 2593402 TI - [A case of complete disruption of right truncus intermedius treated by operation]. AB - A case of right bronchial disruption caused by blunt chest trauma was successfully operated. Patient is a 35-year-old woman who was transferred to our intensive care unit with markedly dyspnea and subcutaneous emphysema. Rupture of right bronchus was suspected by chest x-ray film and bronchial fiberscopy. An emergency thoracotomy was performed with the aid of selective lung ventilation by the use of double lumen endobronchial tube. Right bronchus was completely transected and small part of upper lobe was lacerated. Right bronchus was anastomosed directly with interrupted 3-0 vinyl sutures and laceration of upper lobe was sutured. Postoperative course was uneventful, but postoperative bronchoscopy confirmed slight stenosis of the anastomotic position. Prompt diagnosis by bronchoscopy and emergency thoracotomy followed by selective lung ventilation are mandatory in this patient survival. PMID- 2593403 TI - [Aortic aneurysm associated with coarctation of the aorta]. AB - An 8-year-old female of coarctation of the aorta associated with thoracic aortic aneurysm is reported. Under cardiopulmonary bypass, a 7 cm section of the aorta containing the aneurysm and coarctation was resected and replaced by a 16 mm woven Dacron tube. The postoperative recovery was complicated by chylothorax treated by thoracic aspiration. She is doing well 3 months after the operation. Histologic sections of the resected portions of the thoracic aorta revealed intimal hyperplasia, medial fibrosis and decrease of elastic fibers, especially in the aneurysm. PMID- 2593404 TI - [Effective thromboexclusion for repeating bleeding tendency caused by dissecting aneurysm: a case report]. AB - A 75-year-old woman developed general fatigue and left chest pain in October 1986, and Chest CT showed DeBakey IIIb dissecting aneurysm. During the next 8 months, she repeated abdominal pain, tarry stool and subcutaneous hemorrhage for three times and after an angiography large hematoma at puncture site appeared. The laboratory data showed the decrease in platelet and fibrinogen and the increase in FDP every time when she developed the symptoms. Because this bleeding tendency was thought to be the "local DIC" caused by dissecting aneurysm, we performed thromboexclusion on July 27, 1987. Immediately after the operation, 60 packs of platelet and 3 g of fibrinogen was transfused, then laboratory data remarkably improved and bleeding tendency disappeared. The patient died 12 days after the operation of sudden ventricular tachycardia. At autopsy, precise cause of death was not determined, but the purpose of thromboexclusion seemed to be achieved, because good thrombus formation was observed in the descending aorta and the graft was patent. PMID- 2593405 TI - [Concomitant coronary artery bypass and cholecystectomy: a case report]. AB - A case is reported in which simultaneous surgical correction of coronary atherosclerosis and cholelithiasis was performed. A 71-year-old man was admitted with severe stable angina and right hypochondrial dull pain. Coronary angiograms disclosed severe triple vessel disease, and abdominal echography demonstrated gallstone. He underwent bypass of left anterior descending, diagonal, obtuse marginal, and right coronary arteries with autogenous saphenous vein on cardiopulmonary bypass. The procedure was followed immediately by cholecystectomy. His postoperative course was uneventful. PMID- 2593406 TI - [A case of traumatic tricuspid regurgitation]. AB - Tricuspid regurgitation due to nonpenetrating trauma occurred in a 60-year-old male patient who had received chest trauma in a motorcycle accident. He was admitted because of shortness of breath and palpitation on exertion. On admission physical examinations revealed pulsated and dilated jugular veins, hepatomegaly, and systolic murmur. The chest X-ray film showed an enlarged heart and electrocardiograms revealed complete right bundle branch block. Echocardiography demonstrated systolic prolapse of the tricuspid anterior leaflet into the right atrium. Right atrial v wave pressure was 20 mmHg. Tricuspid valve replacement with a Carpentier-Edwards 33 mm using super interpose method was performed successfully 13 years after the trauma. At operation, it was found that the chordae tendineae of the anterior leaflet was ruptured. PMID- 2593407 TI - [A case of double primary cancer of lung and trachea]. AB - A 57-year-old male was admitted to our hospital with bloody sputum, whose right lung had been resected for squamous cell carcinoma of the lung three and a half years ago. Tomographic examinations and chest CT films showed the presence of tracheal tumor. Histological examinations of the biopsy specimen obtained from tracheal tumor, using bronchofiberscopy, identified squamous cell carcinoma. Trachea was resected in the length of six cartilages and end to end anastomosis was performed. Though lung cancer and tracheal cancer were same histological type, clinical findings confirmed that this case was double primary cancer. Postoperative course was uneventful except for minor leakage of anastomosis site. PMID- 2593408 TI - [The effect of pulsatile perfusion on aortocoronary bypass grafting]. AB - To evaluate the effect of pulsatile perfusion on myocardial protection and peripheral circulation, 23 patients undergoing aortocoronary bypass grafting were studied by dividing two groups; one with pulsatile perfusion technique (11 patients) and the other with non-pulsatile (12 patients). The cardiac functional assessments were made on CI, LVSWI, PCWP, CVP at 3, 6, 12 and 24 hours after the operation and the enzyme (CPK, CPK-MB, LDH, GOT) sampling were performed on 1, 2, 4 and 7 days after the operation. The difference between esophageal and rectal temperature, and urine output during cardiopulmonary bypass, indicating the peripheral circulation, were also measured. From these clinical results, it is concluded that pulsatile perfusion method is to be beneficial in myocardial protection and peripheral circulation during operation of aortocoronary bypass grafting. PMID- 2593409 TI - [Experience of coronary artery bypass grafting using internal mammary artery: operative results with 102 cases during initial three years]. AB - From April 1985 to March 1988, internal mammary-to-coronary artery anastomosis was performed in 102 patients. One postoperative death and one hospital death occurred. Early postoperative arteriography showed good patency rate. The early patency rate was 99% in 53 vein grafts, 95 in 100 internal mammary artery grafts and 75% in 4 gastroepiploic artery grafts. The main obstacles to coronary revascularization with internal mammary artery have been the delicate nature of the arterial grafts and difficult technique in anastomosis. We used the modified "No-Touch Technique" reported by Cheanvechai. Our technique is available to avoid trauma during coronary revascularization with arterial graft and to anastomose correctly. PMID- 2593410 TI - [Three cases of endobronchial hamartoma]. AB - We reported three cases of endobronchial hamartoma. There were some difficulties in diagnosis of the disease by bronchoscopic examination, because the tumors were covered with normal bronchial epithelium. But X ray film and CT film contributed to the diagnosis when calcification of intra-bronchial tumor was observed. Three different modes of operation were performed as extirpation of tumor by wedge resection of upper lobe bronchus, sleeve resection of left S6 segmental bronchus, and right middle lobectomy. PMID- 2593411 TI - [Prophylactic use of cefpiramide (CPM) in open heart surgery]. AB - The concentration of cefpiramide (CPM) in serum and myocardial tissues was measured in 24 patients with open heart surgery. The regimen was given in bolus of 2 g intravenously before the commencement of cardiopulmonary bypass. Blood and tissues of the right atrial appendage and pericardium were surveyed for samples at an estimated interval after the administration of CPM. The concentration of CPM in the blood and the myocardial tissues were consistently efficacious for both gram positive and negative bacterium. The duration and dosage of CPM, selected in the study, were both satisfactory for prevention of infection in open heart surgery. PMID- 2593413 TI - [Indication of the use of pedicled omentum in chest surgery]. AB - The omentum has been known to have a remarkable power of repair through neovascularization and scavenger function. Nine patients have been treated with the pedicled omentum. In 4 patients the omentum was used to obtain healing in the presence of infection. Bronchial fistulas were successfully closed in 3 patients with lung cancer and bronchial anastomotic leakage was repaired in one patient who received carinal reconstruction. In 5 patients, all of them had simultaneous resection of thoracic esophagus, the preventive use of omentum made a good result in two tracheoplasties, one pneumonectomy and one terminal tracheostomy. But one patient with esophago-tracheofistula after irradiation to esophageal cancer developed tracheal necrosis postoperatively. The omentum is useful in the case of postoperative empyema with bronchial fistula especially in patient with lung cancer. In the case of tracheobronchial resection after radiation therapy or with resection of thoracic esophagus, the suture line should be wrapped by omentum to prevent anastomotic leakage. PMID- 2593412 TI - [A modified technic for coronary to graft anastomosis and coronary perfusion in Bentall operation]. AB - From September 1987 to January 1989, we performed 7 consecutive Bentall operations using a modified technique for the coronary artery to graft anastomosis with a satisfactory result. Six patients with annuloaortic ectasia and one with type 1 aortic dissection underwent the operation. After suturing a composite graft to the aortic annulus, side-holes about 8 mm in diameter were made in the graft at points corresponding to the coronary ostia. Then the graft was cut longitudinally on the side of the non-coronary cusp so as to make operative procedure easier. Four buttressed mattress sutures of 4-0 polypropylene thread were placed in the aortic wall around the coronary ostia and connected to the corresponding part of the graft. These threads were tied and then used for running sutures from inside of the graft. Even in a case where the coronary ostium was close to the aortic annulus, this procedure permitted easy and secure accessibility. Additionally, retrograde continuous cold blood cardioplegia via the coronary sinus made Bentall procedure easier and safer. Postoperative angiography revealed no stenosis or deformity of the coronary artery and no leakage from the suture line. All patients are doing well in NYHA functional class I. PMID- 2593414 TI - [Use of the pedicled omentum in chest surgery]. AB - The pedicled omentum finds use in chest surgery for management of complicated problems and prevention of serious complications. Nine patients have been treated with the pedicled omentum. In four patients the goal was preventive, to avoid anastomotic leakage or infection, or to provide a source of neovascularity. In five patients the pedicled omentum was used to obtain healing in the presence of infection. Bronchial fistula, esophageal fistula with pyothorax or mediastinal infections treated successfully. This series demonstrates the efficacy of the pedicled omentum in management of chest problems. PMID- 2593415 TI - [Clinical application of the omentum in chest surgery]. AB - The benefit of the omentum in chest surgery was experimentally evaluated on the basis of findings in relation to recanalization of the bronchial artery in bronchoplasty with and without omental wrapping. The arterial blood supply at the anastomotic sites was observed in the early stage following bronchoplasty using the omental wrapping. Clinical application of the omentum in chest surgery was performed by wrapping anastomotic site at tracheobronchoplasty in 3 cases, bronchial stump coverage after lobectomy or pneumonectomy in 2 cases, repair of bronchial fistula following pneumonectomy in 1 case and repair of bronchopleurocutaneous fistula in pulmonary tuberculosis in 1 case. Six of these clinical cases could have favorable postoperative results. Based on these experimental and clinical results, we consider that the omentum is very useful tissue for wound healing in chest surgery. PMID- 2593416 TI - [Omentum in the management of thoracic surgery: especially its application to tracheobronchial surgery]. AB - Omentum is now not only policeman of the abdomen but also of the thorax. We applied omental pedicle flap in the management of 14 patients with thoracic surgery including chest wall reconstruction, empyema, thoracic skeletal infection and tracheobronchial problems. Especially, tracheobronchial reconstruction using omental pedicle flap for the patient combined with lung cancer (T4N2M0 STAGE IIIB) and asthma under steroid therapy was reported. The case was 71-year-old man with complaint of hemosputum. He had 5-6 year history of bronchial asthma with disturbed pulmonary function of % VC 44%, FVC1.0% 37%. Bronchoscopic study revealed the tumor invading the right side of trachea originating from right upper bronchus with histological diagnosis of moderately differentiated squamous cell carcinoma. Preoperatively, he experienced a heavy asthma attack which was controlled by steroid administration. Following extended right sleeve upper lobectomy, we applied omental pedicle flap around the reconstructed portion for the protection of infection, impaired wound healing due to postoperative steroid therapy and strong tension at anastomoses. Postoperative course was satisfactory. We suggest omental pedicle flap is an effective surgical armamentarium in the management of tracheobronchial surgery for the patient with strong anastomotic tension, immunocompromised condition, preoperative irradiation at bronchial stump and use of drug causing delayed wound healing (steroid, anticancerous drug etc). PMID- 2593417 TI - [Application of omental pedicle to tracheal allotransplantation: an experimental study using adult mongrel dogs]. AB - Methods and results of experimental tracheal allotransplantation using adult mongrel dogs are described in this paper. Omental pedicle flap was used to reconstruct the vascularity of ischemic tracheal allograft. Twenty out of 22 allografts were found to be viable with almost normal tracheal structure and no granulation or stricture. The allografts were proved to be well revascularized from the omental pedicle flap by injection of Indian ink from the right gastroepiploic artery. PMID- 2593419 TI - [The use of omental pedicle flap for treatment in the field of thoracic surgery]. AB - We present a series of 16 consecutive patients who underwent the omental pedicle flap method in the field of thoracic surgery. Fourteen of 16 patients were chronic empyema with bronchopleural fistulae and/or thoracic fistulae. A pedicle of omentum containing the right gastroepiploic artery was passed through a tunnel in the anterior diaphragm into the empyema cavity. It was fixed by mono-filament sutures on the bronchopleural fistulae. All but two patients were cured successfully by single-stage procedures. We also used a omental pedicle flap for mediastinal infection and reconstruction of the chest wall. We conclude that the use of omental pedicle flap is a promising method for treatment of serious infection in the field of thoracic surgery. PMID- 2593418 TI - [Closure method of bronchopleural fistula with omental pedicle flap in three cases following pneumonectomy]. AB - This report presents that successful closure of bronchopleural fistula was performed by using omental pedicle flap for three postpneumonectomy patients. In our department, these cases were experienced among 142 pneumonectomies from January 1984 to July 1989. The initial operations were a pleuropneumonectomy for empyema, a pneumonectomy and a sleeve pneumonectomy for lung cancer. Our technique was direct closure of bronchopleural fistula with omental pedicle flap without thoracoplasty. Although none of them had recurrence of bronchopleural fistula nor other complications in postoperative course, two patients died of cancer. PMID- 2593420 TI - [Clinical experience of omental pedicle flap for bronchopleural fistula]. AB - We present two patients who underwent the omental pedicle flap method for bronchopleural fistula. The first case was a 61-year-old man who developed empyema with bronchial fistula due to recurrent tuberculosis resisted to chemotherapy. He underwent complete muscle and omental flap closure of empyema space. The second case was a 63-year-old man who underwent pneumonectomy for adenocarcinoma of the lung. About two weeks after the operation, a bronchopleural fistula developed at the bronchial stump. He underwent complete omental flap closure of fistula. They are doing well 18 and 9 months following operation, respectively. The omental pedicle flap method is clinically useful as a closure method for bronchopleural fistula because of excellent blood supply of the omentum. PMID- 2593422 TI - [Use of omental pedicle flap for the prevention of bronchopleural fistula after surgery: an unsuccessful case in a management of bronchopleural fistula]. AB - We report a case of bronchopleural fistula after preoperative neo-adjuvant chemotherapy for advanced lung cancer. A 55-year-old man admitted to our institution and was diagnosed to have advanced lung cancer. Right pneumonectomy was carried out after chemotherapy. Parietal pleura and the right main bronchus were thick because of severe fibrosis due to chemotherapy. On the 16th postoperative day, bronchopleural fistula was found. After drainage, further resection of bronchial stump and wrapping with omentum was carried out. However, he died of pneumonia due to repeated bronchopleural fistula. Since this experience, we use omental wrapping procedure in patients undergoing surgery for the hilar type lung cancer after chemotherapy, and conclude that omental wrapping is useful for prevention of bronchopleural fistula. PMID- 2593421 TI - [The use of an omental pedicle flap in the closure of a wide bronchial fistula after pneumonectomy: a case report]. AB - A 52-years-old man with pulmonary hypofunction had a squamous cell lung carcinoma and underwent the right upper lobectomy. Bronchial fistula with lung abscess developed on the 6th post-operative day. So, the right middle and lower lobectomy (completion pneumonectomy) were done. But, bronchial fistula again appeared at the time of weaning from respirator. It increased in size to about 4.0 x 2.0 cm. Then, transposition of an omental pedicle flap for closure on a wide bronchial fistula, and muscular plombage and thoracoplasty for semifilling up a secondary empyema cavity were performed. On bronchoscopy performed 14 days after operation, the fistula was completely closed, and the transposed omentum did not project into the trachea. We accomplished our first aim to close the wide bronchial fistula with omentum. However, he died 59 days after the 3rd operation because we failed to control infection of the remaining empyema cavity of about 100 ml. The management of an empyema cavity remains to be a difficult therapeutic problem. PMID- 2593423 TI - [A case of omentopexy for bronchial fistula and pyothorax following the right completion pneumonectomy with combined resection of pericardium, diaphragm and chest wall]. AB - A 68-year-old male underwent the right completion pneumonectomy with combined resection of pericardium, diaphragm and chest wall. Three months later, he was diagnosed as a bronchial fistula with bloody sputum and decreasing of right pleural effusion level on chest X-ray film. The conservative therapy with pleural drainage and endoscopic practice with fibrin matrix was failed to close a fistula and pyothorax was developed. Therefore, surgical treatment with simple omentopexy without thoracoplasty and/or muscle transposition was performed onto fistula and SILASTIC sheet used for the repair of diaphragm at initial operation was left in the thoracic cavity. Although pleural fluid remained the contamination with bacteria for one month postsurgically, infection did not develop and fistula closed successfully. Moreover, infection did not prolong in the presence of artificial SILASTIC sheet followed by simple omentopexy. Omentopexy may be very useful for the treatment of bronchial fistula with the presence of infection. PMID- 2593424 TI - [A case of hemangioma of the heart]. AB - A-74-year old woman who had suffered from anterior chest pain and palpitation was admitted to our hospital. The chest X-ray photograph showed that the heart was enlarged mildly. We found that the tumor lay in the mediastinum by the echocardiograph and was enhanced at the aortic phase of the radioisotope angiography. In order to obtain the histological specimen, she underwent exploratory thoracotomy. The tumor was diagnosed as a cavernous hemangioma. She has been asymptomatic over 1-year period. The RI angiography seemed to be useful to diagnose the hemangioma of the heart. PMID- 2593425 TI - [A case of isolated anomalous return of bilateral superior pulmonary veins]. AB - A 14-year-old girl was admitted for evaluation of heart murmur. Intravenous digital subtraction angiography (DSA) showed the right superior pulmonary vein drained into the superior vena cava and the left superior pulmonary vein drained into the innominate vein. At the operation, an anomalous bilateral superior pulmonary venous return with an intact atrial septum was confirmed. An atrial septal defect was created and the right superior pulmonary vein was baffled into the left atrium with a pericardial patch. The left superior pulmonary vein was divided and anastomosed to the left inferior pulmonary vein with a expanded polytetra-fluoro-ethylene graft. Post-operative DSA showed satisfactory long-term result of the operation. PMID- 2593426 TI - [A case report of mycotic false aortic aneurysm associated with aortic regurgitation]. AB - The patient was 63-year-old man, who underwent patch closure of VSP 37 days after onset. LVAD was required for weaning from CPB. Mediastinitis occurred after LVAD was removed. The mediastinum was irrigated using diluted antibiotics through the retrosternal drain. He discharged on 79th day postoperatively. False aortic aneurysm and marked AR was pointed out by cineangiography and enhanced CT scan two years after operation. AVR was performed through right thoracotomy, because false aortic aneurysm invaded the sternum. The aneurysmal wall was repaired with patch. Postoperatively, peritoneal dialysis was performed for two days. Flail chest made difficult weaning from the respirator. He died 11 days postoperatively due to respiratory failure. There remains the possibility that mediastinitis resulted in false aortic aneurysm and AR. It was esseutial to remove the foreign materials placed on the aorta for eradication of infection. PMID- 2593427 TI - [Pulmonary embolectomy for a patient of chronic pulmonary embolism]. AB - Chronic pulmonary embolism is resistant to medicinal treatment. This is a report of the successful operation for chronic pulmonary embolism. A 29-year-old man suffered from dyspnea attack twice half a year in spite of intensive anticoagulant therapy. Cardiac catheterization showed pulmonary hypertension of 72/25 mmHg, mean 42 mmHg. Pulmonary angiogram demonstrated emboli in the right pulmonary artery and pulmonary perfusion scintigram revealed large perfusion defect in the right lung. The patient underwent pulmonary embolectomy after the total cardiopulmonary bypass. After surgery, blood gas showed an increased PaO2 from 65 to 77 mmHg. Pulmonary artery pressure decreased to 39/12 mmHg, mean 23 mmHg. Pulmonary arteriogram showed increased pulmonary vascular beds and pulmonary scintigram showed an increased perfusion in the right lung. The patient has been free from symptom and a half year after surgery. PMID- 2593428 TI - [A case of successful surgery for atrial septal defect accompanied with angina pectoris]. AB - A 59-year-old patient with atrial septal defect (ASD) and angina pectoris due to 99% stenosis of the anterior descending coronary artery (LAD) was successfully treated by closure of ASD and coronary artery bypass grafting (CABG) to the LAD #7 with a saphenous vein graft. Preoperatively, the right ventricle was overloaded with high pulmonary arterial pressure (52 mmHg) and anterior segmental wall motion of the left ventricle was reduced probably due to myocardial ischemia. Combined operation, ASD closure and CABG, made these impairments normal and resulted in disappearance of the chest pain and reinstatement to his former job. PMID- 2593429 TI - [The effect of the interval from dinner until retiring on the concentration of lithogenic substances during sleep]. AB - The relationship between the interval from dinner until retiring and the concentration of various substances secreted into the urine during sleep was studied in 69 healthy men who had eaten the same meal. The specific gravity and the concentrations of creatinine, uric acid and magnesium in the morning spot urine were highest in subjects who had retired within 2 hours after dinner. The concentrations of calcium and oxalate in the morning spot urine were highest in those who had retired between 2 and 4 hours. The specific gravity and urinary concentrations of creatinine, uric acid and oxalate were markedly higher in those with the interval less than 4 hours than in those 4 hours or longer. The concentrations of calcium, magnesium and citrate were not significantly different between the two groups. From these results, we recommend that the interval from dinner until retiring be prolonged and fluid be drunk before going to bed to decrease the concentration of lithogenic substances during sleep. PMID- 2593430 TI - [Partial nephrectomy for renal tumors]. AB - We performed partial nephrectomy in 5 patients with renal tumors. In 1 patient with synchronous bilateral renal cell carcinoma, radical nephrectomy was conducted simultaneously for the contralateral kidney. The second patient had a transitional cell carcinoma of the renal pelvis of the contralateral side, for which the pelvis was resected simultaneously. In the remaining 3 patients the contralateral kidney was normal. In these patients the tumor was less than 3.0 cm in size and localized in either the upper pole or peripheral region, for which partial nephrectomy was performed. The weight of the resected kidney ranged 6 to 35 g with a mean of 18.2 g. The tumor size was 1.8 to 4.0 cm, the mean being 2.4 cm. Tumor grading was renal cell carcinoma grade 1 in 2 patients, grade 2 in 2 patients and oncocytoma in one patient. In all patients the tumor was encapsulated with a pseudocapsule with no involvement of the perinephric fat, venous or regional lymph nodes, and the tumor was diagnosed as pT2V0N0M0, stage I. In none of the patients intraoperative or postoperative complications developed with renal function of the operated kidney normal. The follow up interval after the operation was 5 years in 1 patients and 6 months to 1 year and 2 months in the remaining 4 patients. All patients have survived without metastasis or local recurrence in the operated kidney. We believe that partial nephrectomy is worth performing in selected patients with renal cell carcinoma not only in those having lesion in solitary kidney or bilateral kidneys but also in those whose function of the contralateral kidney is normal. PMID- 2593431 TI - [Mainz pouch using the appendix as the efferent limb]. AB - Mainz pouch procedure requires intussuscepted ileum only at the efferent limb because ureters are tunneled into the colon wall in stead of the intussuscepted ileum as done in the Kock pouch procedure. We modified the Mainz pouch procedure using the tunneled appendix as the efferent limb in which intussuscepted ileum was no longer required. Four patients, three with bladder cancer and one with prostatic cancer, underwent this procedure. After total cystectomy and pelvic lymph-adenectomy the pedicled ileocecal segment was isolated. The appendix with the intact vascular supply was separated from the ileocecal segment. After the pouch was constructed, both the ureters and the appendix were tunneled into it. The pouch was then drained by a 24 Fr nephrostomy catheter. The ureters were splinted. The pouch was closed in one layer with locked running sutures. Three patients had ureteral strictures, 2 of which were corrected by percutaneous dilatation. The third one required persistent nephrostomy drainage. The appendix of all 4 cases functioned well as the efferent limb, preventing urinary leakage and allowing easy catheterization. Three of the 4 patients satisfied with this type of urinary diversion. The modified Mainz pouch procedure may be very useful because it does not require any staples to fix the intussuscepted ileum nor a long intestinal segment. Patients whose appendix can not be utilized may be candidates for the original Mainz pouch procedure. PMID- 2593432 TI - [Recovery process of injured ureters in dogs]. AB - This paper is the 13th report in a series of studies on the application of microexplosion to medicine and biology. The recovery process of injured ureters was investigated in the day. The 60 ureters of 42 mongrel dogs were used. The ureter was injured with a nail, punch or surgical knife. The "pierced injury" was passed through the ureter with a nail of 1 mm or 2 mm in diameter, the "punch injury" was punched out in the ureter by a puncher of 1 mm or 2 mm in diameter and the "cut injury" was cut in the ureter 5 mm or 10 mm in size with a surgical knife. The recovery process of the injured ureter was observed in each of the two ureters 3 days, 1 week, 3 weeks, 6 weeks and 12 weeks after the injury by means of IVP, for macroscopic and microscopic findings. The results were as follows: 1) In IVP, it was observed that the 1 mm pierced injury resulted in no urine leakage after 3 days, that the 2 mm pierced injury and 1 mm punch injury in no urine leakage after almost 1 week and that the 2 mm punch injury and 5 mm cut injury and 10 mm cut injury in no urine leakage after almost 3 weeks. Hydroureter due to tissue edema was observed only in one ureter with a 10 mm cut injury after 1 week. No ureteral stricture, hydronephrosis or hydroureter was observed in the other ureters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593433 TI - [Experimental studies for urinary incontinence. Effect of beta 2-agonists on the vesicourethral function]. AB - Terbutaline and clenbuterol, which are both selective beta 2-adrenoceptor agonists, produced a concentration-dependent decrease in contractile force of in vitro rabbit detrusor and proximal urethral smooth muscle. Conversely, terbutaline and clenbuterol produced a concentration-dependent increase in basal tension of in vitro rabbit external urethral striated muscle. Clenbuterol, orally administrated, produced an increase in urinary bladder capacity in cystometry and also an increase in maximal urethral closure pressure in urethral pressure profile. These results suggest that the beta 2-adrenoceptor agonist may be beneficial for urinary incontinent patients. PMID- 2593434 TI - [Disappearance of bacteriuria after transurethral prostatectomy with special reference to the sensitivity to the used antimicrobials]. AB - From 333 patients who underwent transurethral prostatectomy between May 1983 and April 1987, 123 strains of bacteria were isolated before surgery. Although all of the cocci which were sensitive to the used antimicrobials disappeared after surgery, significant difference was not observed between the disappearance rates of sensitive and non-sensitive gram-negative bacilli (disappearance rates were 86.4% and 77.8%). About two-third (34/57) of postoperative bacteria were those not isolated before surgery and patients with preoperatively infected urine had more chance than patients with sterile urine to develop infection by bacteria which was not pre-operatively detected. Precise preoperative condition is not known at the time of surgery and the sensitivity of preoperatively reported bacteria is, although important, not a sufficient information. We can only guess bacteria which might become apparent after prostatectomy. PMID- 2593435 TI - [VM-26 and VP-16 salvage therapy for refractory germinal testicular cancers]. AB - Thirteen evaluable patients with germinal testicular cancers failing to be cured with first-line therapy (refractory) were treated by salvage chemotherapy. Ten patients received salvage chemotherapy with VM-26 (50 mg/m2, twice a week X 6 weeks) and cisplatin (CDDP, 20 mg/m2 for 5 consecutive days every 3 weeks for 3-4 times) (P-VM), 3 patients were also treated by radiation therapy, and 3 patients received VP-16 (100 mg/m2) and CDDP (20 mg/m2) (P-VP), all given daily for 5 consecutive days every 3-4 weeks for 4-5 courses. Of 13 evaluable patients, 6 (46%) had complete response (CR) (three cases were also treated with radiation therapy), 4 (31%) achieved partial response (PR), and 3 (23%) had no response. Limited to 7 patients treated with only P-VM therapy, there were 3 (43%) CR and 4 (57%) PR. Nine patients (69%) remained alive and were continuously disease free 18 to 84 months (median 48 months). Hematologic toxicity was severe, but with no death related to sepsis. Salvage chemotherapy with VM-26 or VP-16 and cisplatin offers potentially curative treatment to patients with refractory testicular cancer. The addition of radiation therapy to salvage chemotherapy was also effective. PMID- 2593436 TI - [Abnormal findings on IVP study manifested by invasion of pancreatic carcinoma]. AB - Pancreas carcinoma is sometimes notoriously difficult to diagnose. Although it is well known that pancreas carcinoma can invade contiguous organs, no attention to urinary tract involvement is paid. Although urinary tract is involved at a late stage, it may represent the first symptomatic evidence of the disease. In such cases, pancreas carcinoma can be presented initially as a urologic disease and patients' symptom may not be differentiated from urinary tract diseases. Computed tomographic (CT) images and medical records of 50 patients with histologically proved pancreas carcinoma were reviewed. There were 10 cases with urinary tract involvement. IVP study was performed in 8 of these cases. Of the 10 cases 8 were male and 2 were female. There was a high incidence of left urinary tract involvement (left:right:bilateral = 7:2:1). Nine cases were pancreas body and tail carcinoma and 1 case was pancreas head carcinoma. The stages were all in IV. All cases were with confirmed evidence of urinary tract involvement at autopsy within 4 months following CT studies. We compared those IVP, CT images and findings of autopsy. In these patients, 4 cases showed direct invasion of the kidney, 5 cases ureteral involvement and 1 case metastasis to the urinary bladder and ureters. IVP showed inferior displacement of the kidney and/or ureteral displacement on the affected side, as well as collecting system distortion, including hydronephrosis secondary to ureteral compression. CT scan showed an abnormal mass which is contiguous to the pancreas, showing compression of the kidney and/or retroperitoneal extension with ureteral involvement. Metastasis to the urinary bladder is also identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593437 TI - [Separation and properties of N-acetyl-beta-D-glucosaminidase from human seminal plasma]. AB - N-acetyl-beta-D-glucosaminidase from human seminal plasma has been separated by the cellulose acetate electrophoresis into two components, isoenzyme I and II. The two isoenzymes are readily separated on a DEAE-Sephadex column. Isoenzyme I which has adsorbed to the column, is eluted at 0.1 M NaCl, whereas isoenzyme II has passed through the column. The following enzyme properties have been obtained: 1) Both isoenzymes show the same Km values (0.27 X 10(-3) M) towards sodio-m-cresol-sufonphtaleinyl-N-acetyl-beta-D-glucosaminide . 2) Both isoenzymes show the same pH optima of 5.4. 3) Optimal temperature for isoenzyme I is 50 degrees C, while that for isoenzyme II is 65 degrees C. Isoenzyme II is heat stable, while isoenzyme I is easily denatured by heat. These characteristics of isoenzyme I and II coincide with previous reports of NAG A and B from the spleen and the kidney, respectively. The activity ratio of isoenzyme I and II has been studied for the reproductive tissues. The % ratio of isoenzyme I and II in the epididymal head is 62 and 38, that in the epididymal tail is 42 and 58, and 38:62 in the seminal vesicle, 35:65 in the prostatic gland and 27:73 in the seminal plasma. PMID- 2593438 TI - [Clinical assessment for 152 total cysto-urethrectomized bladder cancers]. AB - During the period from July 1975 to September 1987, 325 patients with bladder tumor were treated in Kinki University. 152 of them were treated by total cystourethrectomy. On these 152 cases clinical assessment was performed from several aspects. The 152 patients consisted of 111 males and 41 females. The overall mean age was 64.6 years old. Tumor with the grade G1 was found in 14 patients, G2 in 65 and G3 in 73. As for the stage, CIS was seen in 21 patients, T1 in 60, T2 in 22, T3a in 23, T3b in 15 and T4 in 11. The 5 year survival rate of the total patients was 62%. The rate by grade was 78% in G1, 66% in G2 and 55% in G3; the rate by stage was 75% in CIS, 77% in T1, 59% in T2, 57% in T3a, 36% in T3b and 13% in T4. When the stage became T3b, the survival rate fell remarkably. Lymphadenectomy was performed in 136 of the 152 patients and metastasis was observed in 19 patients of the former. Their 5 year survival rate was 22% in patients with lymph node involvement and 70% in those without lymph node involvement; the difference was significant. Furthermore, the relation between the macroscopic appearance and the survival rate was studied. The size, multiplicity and growth pattern (papillary or nodular) were likely to be related to the survival rate of bladder tumors. We believe that these clinical assessments for bladder tumors will contribute to an improvement of the therapeutic results for the tumors together with studies on their natural history. PMID- 2593439 TI - [Effect of furosemide on the obstructed kidney]. AB - The effect of furosemide on the obstructed kidney was studied in dogs. In control kidneys (n = 4) the renal blood flow (RBF) was increased transiently after intravenous infusion of 20 mg of furosemide; from 12.9 +/- 1.2 to 14.8 +/- 1.4 ml/min/kg.B.W. No change in the renal pelvic pressure was observed. Urine flow increased from 0.47 +/- 0.12 to 4.98 +/- 1.15 ml/min at 20 minutes after furosemide administration. Increases in the fractional fluid excretion rate (V/GFR), the fractional sodium excretion rate (FENa) and the fractional potassium excretion rate (FEK) were observed and the maximum values were obtained at 20 minutes after furosemide administration. In two-week unilateral incompletely obstructed kidneys (incomplete UUO; n = 5), RBF was lower than that of the control kidney, whereas a tendency of transient increase was also noticed after furosemide administration; from 8.4 +/- 1.9 to 10.5 +/- 2.3 ml/min/kg.B.W. The renal pelvic pressure increased immediately and transiently after furosemide infusion. Increase in the urine flow was significant, but the value was lower than that of control, and the maximum value was marked at 20 minutes after furosemide administration. V/GFR, FENa and FEK were also increased in incomplete UUO, but the peak values were lower than those of control. In two-week unilateral completely obstructed kidneys (complete UUO; n = 5), RBF was markedly decreased (3.14 +/- 0.38 ml/min/kg.B.W.), and no significant increase was noticed after furosemide administration. The renal pelvic pressure was gradually and continuously increased after furosemide infusion. The fractional excretion rate of pelvic urine components was variable. In particular, V/GFR was significantly increased 60 minutes after furosemide administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593440 TI - [Long-term results of M-VAC for the treatment of advanced urothelial cancer]. AB - Total of 37 patients with measurable lesions originating in advanced urothelial cancers received M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) combination chemotherapy and have been followed for a minimum of 12 months. The study included initial diagnoses of 24 bladder cancers and 13 upper urinary tract cancers in patients whose mean age was 62 years. The patients received a mean of three cycles of M-VAC. Clinical complete remission was observed in five of the 37 patients (13.5%) and partial remission was achieved in 10 patients (27.0%) after mean treatment of 2.4 and 2.1 cycles, respectively, for an over-all objective response rate of 40.5%. The mean duration of response was 11.6 +/- 7.1 months and 4.4 +/- 3.5 months for complete and partial remissions, respectively. A mean of 5.2 +/- 1.7 cycles of M-VAC was given for complete remissions and 3.5 +/- 1.4 cycles in partial remissions. An over-all survival rates after one and two years were 28.125% and 5.859%, respectively. Two of the five patients who had once marked complete remissions died after a mean survival time of 14.5 +/- 4.5 months and three survived with a mean duration of 20.3 +/- 5.4 months. Meanwhile, all of the patients who had achieved partial remissions died after a mean survival of 9.1 +/- 5.4 months except for one patient who survived more than 12 months. These results indicate that M-VAC combination chemotherapy for advanced urothelial cancer is extremely efficacious in initial responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593441 TI - [Two cases of ectopic prostatic tissue in the prostatic urethra]. AB - Two cases of ectopic prostatic tissue or adenomatous polyps with prostatic type epithelium in the prostatic urethra were reported. They were 30-and 33-year-old males suffering from gross-hematuria and from urethral pain on urination with terminal gross-hematuria. Endoscopic examination revealed papillary lesions from the dilated orifice of the prostatic utricle. Biopsied pathology demonstrated a tissue similar to that of the prostatic gland. PSA (prostatic specific antigen) stain using immunohistochemical methods was positive. Histogenesis and the importance of this lesion particularly as a cause of hematuria in the young male adult were discussed. PMID- 2593443 TI - [The mechanism of blood outflow from the cavernous tissue of human penis by computer graphics]. AB - There are two theories concerning the mechanisms of human penile erection and its maintenance. One theory goes that the artery responsible for blood inflow into the cavernous space relaxes, while the vein responsible for blood outflow actively contracts. The other theory asserts that no active closing mechanism in present in the penile venous system, but rather the erection is totally controlled by the amount of blood inflow. In order to corroborate the vascular construction of the penis, we prepared serial sections of the penis specimens obtained at autopsy and observed these sections by light microscopy, and we investigated the construction of veins which let blood flow out from the corpus cavernosum penis by computer graphics. As a result, we were unable to find any valves in the blood outflow system. Moreover, efferent vessels were seen to let blood flow from the cavernous spaces, after running immediately below the tunica albuginea for a small distance, to the tunica albuginea, running obliquely through inner veins toward the outside of the tunica albuginea in the direction of the long axis of the penis; then these veins are continuous to the veins on the tunica albuginea. From the above-mentioned structures we can infer the following mechanism of penile erection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593442 TI - [Clinical application of Sonolith 2000 type B on extracorporeal shock wave lithotripsy for upper urinary tract calculi]. AB - This report describes the results of clinical trials of the second generation extracorporeal shock wave lithotriptor (Sonolith 2000 Type B) in patients with upper urinary tract stones. The studies were carried out on 101 cases at the Departments of Urology, Juntendo University School of Medicine, Kanto Teishin Hospital and General Daiyukai Hospital from Nov. 1987 to Jun. 1988. The location of stones were renal calyx and pelvis in 84 cases, ureteropelvic junction in 7 cases and upper ureter in 12 cases (2 of them had multiple stones at different levels). The average number of treatment per a patient was 1.25, and that of shock waves delivered per treatment was 1798. Ultrasound localization has been effective in all cases. The rate of destruction of the stones was 100% in the kidney, 66.7% in the upper ureter, with an overall average of 95.0%. On the X-ray film obtained six weeks after ESWL treatment, the stone free rate was 53.5%, and the effectiveness rate was 89.1%, including the cases of stone free and cases with fragments smaller than 5 mm. No serious adverse effect was observed, although there were mild transient hematuria in all cases and pyrexia (more than 38.0 degrees C) in 7 cases (6.9%). The procedure was performed safely in the majority of patients without anesthesia. In 10 cases, we applied anesthesia (epidural anesthesia in 3 cases, and local anesthesia in 7 cases) for the prevention of pain. It is concluded that ESWL treatment using Sonolith 2000 Type B is as effective as other types of shock wave lithotriptor previously applied to urolithiasis without serious clinical complication. PMID- 2593444 TI - [Survivals of incidental renal cell carcinoma]. AB - Between January 1987 and July 1988, 151 cases of renal cell carcinoma were nephrectomized at out institutions. Among them 41 cases (27.2%) were diagnosed incidentally. The ratio of incidental carcinoma has been increasing steadily in the past decade. Thirty-four of these cases (82.9%) were detected by ultrasound, 4 by computerized tomography, and three by excretory urography. Twenty-eight of these cases were found serendipitously during examination for other diseases, while others had no symptoms at all. Only 8 of these cases (19.5%) showed microscopic hematuria. The stage and the grade of these incidental carcinoma were significantly lower than those of symptomatic carcinoma (p less than 0.001). The survival rate of the former was better than that of the latter (p less than 0.01), especially in patients with pT1-2b tumors (p less than 0.05) or with tumors smaller than 10 cm in diameter (p less than 0.05). PMID- 2593445 TI - [Results of the treatment of prostatic cancer]. AB - Two hundred and twenty patients with prostatic cancer were treated in our clinic during the past ten years between April, 1977 and March, 1987. The age distribution was from 45 to 91 years old and more than half of patients were in seventies. Stages A, B, C and D were 3.5%, 19.7%, 21.2% and 55.6%, respectively. Hormonal therapy was given in 175 cases (79.5%) as an initial treatment. The first therapy showed effectiveness in 181 (83.8%) of 216 cases; in 153 (87.4%) of 175 cases treated by hormonal therapy. Reactivation after the initial treatment was observed in 59 (32.6%) of 181 cases; in 48 (31.4%) of 153 cases treated by hormonal therapy. The interval between the start of treatment and reactivation for the stage D was significantly shorter than that for the other stages. Elevation of serum alkaline-phosphatase levels, accelerated erythrocyte sedimentation rate and hydronephrosis were significant risk factors for reactivation. Of the 220 cases, 51 (23.2%) died of advanced cancer. The overall 5 year survival rate was 41.2%. High grade and high stage were significantly related to the poor prognosis. In our studies, as hormonal therapy, maintenance on 100 mg of diethylstilbestrol diphosphate daily was found effective for the treatment of prostatic cancer. PMID- 2593446 TI - [Reconstructive surgery of obstructive disease of the upper urinary tract]. AB - Efficacy of reconstructive surgery for the obstructive disease of the upper urinary tract was evaluated. Reconstructive surgery was performed in 75 units of the urinary drainage system of 72 patients between July, 1977 and December, 1987. 44 patients were male and 28 were female. The patients ranged in age 1 to 71, mean +/- S.D. being 43 +/- 14 years old. Original diseases were postoperative scar, scar due to the calculi, injury, retroperitoneal fibrosis, ureteritis, tuberculosis, amyloidosis and multiple ureteral diverticulum. The surgery consisted of ureterocalicostomy, renal descensus, descent of right renal vein, uretero-ureterostomy, ureteroneocystostomy (to the dome of the bladder), psoas bladder hitch and renal autotransplantation. Renal autotransplantation was chosen instead of ileal substitution to preserve the continuity of the urinary drainage system, when the upper urinary tract was extensively damaged. The obstructive change of the upper urinary tract improved or disappeared in 66 of 75 units. However, it persisted in 9 units, which were treated with ureterocalicostomy (wrong technics; in 4 units), ureteroureterostomy (wrong choice of the procedure; in 4 units) and autotransplantation (cessation of anti tbc drugs; in 1 unit). In 3 of these 9 units, additional reconstructive surgery was necessary. One patient who was treated with autotransplantation, died of massive bleeding from rupture of arterial anastomosis on 14th postoperative day. No other life-threatening complications were observed. Deterioration of the renal function was observed in two severely damaged kidneys which were performed autotransplantation, although the obstructive change of their urinary tract completely disappeared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593447 TI - [Pressure-flow study after percutaneous nephrolithotripsy]. AB - In 46 patients treated with PNL in our hospital, the intervals from PNL to removal of a catheter indwelled in the nephrostomy were studied. The intervals were longer in the cases with ureteral stones than those with renal stones probably because of the different degrees of obstruction. To investigate the degree and the interval of upper urinary tract obstruction after PNL, Pressure flow Studies were performed every or every other day after PNL in 5 cases with renal stones and 5 cases with ureteral stones, selected from 46 cases. In Pressure-flow Studies, intrapelvic pressures were measured while saline mixed with pigment was being dripping at a rate of 5 ml/min into the renal pelvis through the nephrostomy catheter. Saline initially reached into the urinary bladder at an average of 4.8 days after PNL (range 3 to 7 days) with a mean intrapelvic pressure of 37.6 cmH2O (range 28 to 52 cmH2O) in the cases with renal stones and at an average of 9.2 days (range 7 to 12 days) with a mean intrapelvic pressure of 27.0 cmH2O (range 9 to 43 cmH2O) in the cases with ureteral stones. Pressure-flow Studies were performed again a few days after the initial passage of saline into the urinary bladder in 2 of 10 cases. The intrapelvic pressures, 16 cmH2O and 13 cmH2O, respectively, several days after the initial passage of saline were lower than those, 35 cmH2O and 43 cmH2O, respectively, at the initial passage of saline. Therefore, it was likely that the proper interval of indwelling catheter after PNL was about 7 to 8 days, in the cases with renal stones and about 11 to 12 days in the cases with ureteral stones. PMID- 2593449 TI - [Clinical evaluation on Le Duc-Camey antireflux ureteroileal implantation]. AB - Le Duc-Camey antireflux ureteroileal implantation was evaluated clinically; by applying to various types of urinary reconstruction utilizing the ileum. Nineteen ureters in 10 cases including five Kock continent ileal urinary reservoirs (Kock pouches); five ileal conduit urinary diversions and one Goodwin ileocystoplasty were performed from March 1987 to August 1988. Male and female ratio was 8 to 2 and the average age was 61.7 years old. The post operative observation period was 13.9 months on the average. The outline of the operative procedure was as follows: a 3 cm sulcus was created in the mucosa along the long axis of the ileum; the ureter was passed from the serosal surface to the luminal surface and the adventitia of the ureter and the mucosa were sutured at three points in each side using 3-0 absorbable ligature to implant the ureter in the mucosal sulcus. The ureteral end was spatulated 3 mm in the upper wall and it was fixed to the mucosa by three stitches. A ureteral stent catheter, 7-8 Fr. in diameter, was indwelled in the ureter. Additional stitches were placed to strengthen the fixation on the outside surface of Kock pouches or a Goodwin ileocystoplasty. The afferent limb was not fabricated in Kock pouches because ileoureteral reflux could be prevented by the implantation technique on the pouch. Radiological evaluation was done taking IVP, loopography, pouchgraphy and cytography periodically after the operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593448 TI - [Gene transfer into renal cancer cell by electroporation]. AB - For the purpose of elucidating the role of oncogenes like c-myc in renal cell carcinoma, the methods of introducing exogenous genes into human cells might be powerful tools. In the present study, the electroporation gene transfer method was investigated for its application to renal cancer cells. A mixture of ACHN cells (human renal cancer cell line, which cannot grow in the presence of neomycin) and DNA of neomycin-resistant genes with SV 40 promoters was exposed to electric pulses from an electroporated (Bio-Pulser 101, UNISOKU). And the cells were cultured in a medium containing Geneticin (neomycin analog) for 3 weeks. Then, the number of formed neomycin-resistant neoR colonies was counted. In the cells of neoR colonies, the existence of neoR genes and their expression were confirmed by Southern and Northern blot gene analyses. The transformation efficiency (number of neoR colonies/inoculated cells) was positively correlated with cell densities, DNA concentrations, and discharged voltages under our experimental conditions. The transformation efficiency was 1.3 - 3.3 x 10( 4)/cell in the condition of 1 x 10(7) cells/ml, 1 microgram DNA/10(6) cells, and 2 kV/cm. These results suggest that the electroporation gene transfer method is applicable for the study of phenotypic alterations after introducing oncogenes into human renal cancer cells. PMID- 2593451 TI - Origin of another species. PMID- 2593450 TI - [A case of inverted papilloma with subsequent heterotopical recurrence of transitional cell carcinoma]. AB - A case of inverted papilloma with subsequent heterotopical recurrence of inverted type transitional cell carcinoma is reported. A 24-year-old man had a medical examination of our hospital with chief complaint of asymptomatic macroscopic hematuria on October 23, 1982. Cystoscopy revealed a smooth surfaced and finger tip sized tumor at the bladder neck. Because of the large bulk and the location of the tumor, the tumor was resected through cystotomy. After histological examination, the tumor was diagnosed as inverted papilloma. Cystoscopy was repeated every 3-6 months. The tumor recurred 4 times heterotopically, 19, 35, 43 and 53 months after the initial surgery. The pathological examinations of these tumor specimens showed transitional carcinoma mostly of inverted growth. Most of the urologists and pathologists believe inverted papilloma to be a benign neoplasm, but several reports and this case suggest the possibility of recurrence and malignant transformation of inverted papilloma. PMID- 2593453 TI - The complexities of diabetic neuropathy. PMID- 2593452 TI - The risks of underinsuring. PMID- 2593454 TI - [Midwifery work is both delightful and rewarding]. PMID- 2593456 TI - [Many challenges in maternal health care]. PMID- 2593455 TI - [Finnish maternity care at the crossroads]. PMID- 2593457 TI - [Students' thoughts on constructive changes in maternity care]. PMID- 2593458 TI - [Specialization in maternity care for the benefit of pregnant mothers. Interview by Arja Laiho]. PMID- 2593459 TI - [Much has been done but everything is not ready yet]. PMID- 2593460 TI - [A taxonomic study on a mycobacterium which caused a skin ulcer in a Japanese girl and resembled Mycobacterium ulcerans]. AB - A taxonomic study has been made on a mycobacterial strain isolated from skin ulcer lesion of a 19 year-old Japanese girl who has lived only in Japan. By numerical classification, in which 108 characters were used, 6 isolates of this strain formed one cluster together with Mycobacterium ulcerans strains. However, the isolates were distinguished from the M. ulcerans strains, forming a subcluster. The isolates were differentiated by the characters shown in Table 2 from authentic M. ulcerans strains. The mycolic acids of the strain ATCC 33788 isolated from Japanese girl were distinguished from those of the type strain ATCC 19423 of M. ulcerans. The number of carbon atoms of alpha-mycolate of the former centered at 80, whereas those of the strain ATCC 19423 at 76. The number of carbon atoms of the alpha-unit was 24 in both strains and the number of double bonds was 2 in both strains. The strain ATCC 33788 showed a 100% similarity with the strain ATCC 19423 in DNA hybridization. In view of the above results, we have concluded that the strain belongs to a new subspecies of M. ulcerans (M. ulcerans subsp. shinshuense). Until now, M. ulcerans infection has occurred only in three area of the world, Africa, Oceania, and South and Middle America. Our case is the first case of M. ulcerans infection discovered in an area other than the above. However, the strain was not the same as the M. ulcerans described previously but differed from it in mycolic acids and some biological and biochemical characteristics. PMID- 2593461 TI - [Pulmonary tuberculosis and diabetes mellitus--report of the 29th B series of controlled trials of chemotherapy. Cooperative Study Unit of Chemotherapy of Tuberculosis of National Sanatoria in Japan (CSUCTNS)]. AB - The data obtained from 315 cases of pulmonary tuberculosis with positive sputum and complicated with diabetes mellitus were collected and the results were summarized as follows; 1) Patients were collected from admitted patients in 1983. 2) Ratio of male to female was 3.3 to 1. 3) Most patients (80.1%) were in the age groups over 50. 4) Patients were divided into two groups according to the degree of control of diabetes: one group was well controlled and the other was not. Bacilli negative conversion rate was 98.4% in the well controlled group and 91.6% in the other group at 6 months, and the difference was statistically significant. PMID- 2593463 TI - [Situation of tuberculosis in the world and the role expected of Japan in the global fight against tuberculosis]. AB - The whole world is divided into 3 groups by the magnitude of tuberculosis problem: namely, developed countries in which tuberculosis is already a minor health problem and continues to decline; NIES and some oil-producing countries in which tuberculosis started to decline significantly; and most developing countries in which tuberculosis is still highly prevalent and no or only a slow decline. Number of new smear positive pulmonary tuberculosis in the whole world in a year is estimated at about 4.5 million, and adding smear negative pulmonary tuberculosis and extra-pulmonary tuberculosis, total number of new tuberculosis patients amounts to 9 to 10 million, and nearly 3 million persons die every year from tuberculosis, and 97% of these cases occur in developing countries. Failure of tuberculosis control in most developing countries could be explained by slow economic development of financial crisis, which caused poor allocation of budget for health including tuberculosis programme and slow development of primary health care. Activities of tuberculosis supervisory teams are weak. Tuberculosis programmes succeeded in developed countries could not be implemented easily in developing countries. New obstacles to the rapid decline of tuberculosis are the epidemic of AIDS, movement of population and lowering concern on tuberculosis problems, and tuberculosis will remain as one of serious global health problems at least for coming several decades. Maintenance of research and training facilities for tuberculosis is needed, however, they have been disappearing in developed countries. Facilities in developing countries might have difficulties to maintain unless financial and technical support is given from developed countries. Japan is the second biggest economic power in the world, and it is our duty to increase ODA for developing countries. In the field of health, Dr. Nakajima started to work as the director-general of WHO since 1988. We have to intensify our technical cooperation in health. As we succeeded to control tuberculosis in the past 40 years and still maintain research and training facilities for tuberculosis, they should be used for the sake of developing countries. Multi-and bi-lateral cooperation in tuberculosis control should also be intensified. The author would like to urge members of the Japanese Society for Tuberculosis to talk about the importance of tuberculosis problem and role expected to Japan in the global fight against tuberculosis to people outside the society so as to have appropriate understanding on global tuberculosis problems. PMID- 2593462 TI - [A case of miliary tuberculosis associated with ARDS, DIC and bilateral pneumothorax]. AB - We reported a case of 64 a year-old male patient of miliary tuberculosis associated with ARDS, DIC and pneumothorax, who had a history of gastric ulcer and pulmonary tuberculosis. On admission his chief complaints were fever, fatigue, palpitation, appetite loss and weight loss, and most noticeable abnormalities were bleeding from the gastric ulcer and miliary shadow on the chest x-ray film with hypoxemia. On the day after admission to the hospital he was diagnosed as ARDS as he showed severe hypoxemia due to extensive tuberculous infiltration in bilateral lung fields, and treatment with antituberculous drugs and steroids were started. On the third hospital day DIC appeared on laboratory data, Gabexate mesilate (FOY) for DIC and respirator for ARDS were introduced. Two weeks later pulmonary infiltration, PaO2 and general condition were somewhat improved. On the 15th day after admission pneumothorax occurred on the right side, and on the 20th day on the left. Tube drainage of both pleural cavities, and instillation of OK-432 and Fibrinogen HT into the right pleural cavity were done, but it showed no effect. Two months after admission pouring Fibrinogen HT and thrombin into the left B1+2 and right B1 with cannula washing pipe through the instrument channel of bronchoscope was carried out. A few days later air leakage stopped and collapsed lungs were completely expanded. This method is effective in the case of incurable pneumothorax with pulmonary hypofunction. PMID- 2593465 TI - [Development of acute focal myocardial dystrophy during diagnostic transesophageal electric stimulation of the heart]. PMID- 2593464 TI - [Muramyl dipeptide derivative and its clinical application]. AB - Muramyl dipeptide (MDP) and its synthetic derivatives which comes from the major constituent of bacterial cell wall has various biological activities as host defence mechanisms. One of the synthetic MDP derivatives, MDP-Lys (L 18), muroctasin has potent biological activities with less adverse reactions among various MDP derivatives. Muroctasin has proved to be safe to use clinically as the results of phase I clinical study. We attempted to evaluate its clinical usefulness and safety from the view point of restorative activity in leukopenia that was induced by cancer chemotherapy in patients with malignancies. It is concluded that muroctasin is effective as well as useful on the restorative activities against leukopenia in lung cancer patients after cancer chemotherapy, with the optimal daily dosage of 200 micrograms for six times by subcutaneous injections through phase II and phase III clinical cooperative studies in Japan. Supposed mode of action of muroctasin for granulocytosis may be the results of CSF production due to stimulation of macrophage by muroctasin. This first clinical success of restoration of leukopenia in patients with cancer receiving cancer chemotherapy by MDP derivative, muroctasin, might be not only advantageous for cancer chemotherapy and/or radiation therapy but also for preventing infections occurring in compromised host due to neutropenia in cancer patients by means of cytotoxic cancer chemotherapy or irradication. PMID- 2593466 TI - [Functional state of blood platelets in arterial hypertension and the changes in serotonin-containing cellular granules]. AB - The study was undertaken to examine the status of the granular apparatus and platelet aggregability in 9 healthy donors and 18 patients with arterial hypertension (AH), including 14 with essential hypertension (EH) and 4 with symptomatic forms of AH. Among the patients, a group of 8 EH patients was singled out, who had, compared with normal, reduced relative volumes of electron dense platelet granules (from 17.9 +/- 2.0 to 5.3 +/- 0.6%). The group also showed lower platelet serotonin levels (from 67.3 +/- 5.3 to 17.6 +/- 3.7 ng per 10(8) cells; p less than 0.001) and a 2-fold decrease in the transport factor of acridine orange across the cytoplasmic and granular membranes as compared to normal. A positive correlation was established between the amounts of cellular serotonin and the relative volume of platelet granules (r = 0.850; p less than 0.001). PMID- 2593467 TI - [Clinico-hemorheological aspects of the course of hypertension]. AB - Seventy nine patients with essential hypertension were studied. Group 1 showed profound changes in hemorheological parameters, Group 2 exhibited moderate changes in this system. A more severe course of essential hypertension was found in patients from Group 1. The clinical picture of the disease was more favorable, and antihypertensive therapy was more efficient in patients from Group 2. It was concluded that the initial rheological background and the status of the hemolytic system largely governed the clinical course of essential hypertension and the efficacy of the therapy. PMID- 2593468 TI - [Comparative study of hemolysis in patients after implantation of Soviet-made artificial heart valves and spherical and angle-opening disc closing devices]. AB - Intravascular hemolytic parameters were studied in 40 patients after implantation of Soviet-made cardiac values with a ball versus angle-opening disc closing device. It was found that with the angle-opening disc closing cardiac valves "LIKS" and "EMIKS", hemolysis developed considerably more infrequently and was less marked than with ball valves. A significant difference was found between the activity of lactate dehydrogenase and the levels of haptoglobin in the compared groups of patients (p less than 0.05). PMID- 2593469 TI - [Atherogenic dyslipidemia in adolescents: its relation to ischemic heart disease in their fathers and the possibility of its prognosis]. AB - Comparison of a group of adolescents aged 11-16 years whose fathers had angiographically documented coronary atherosclerosis in youth with those matched by sex and age whose parents were clinically healthy yielded the following discriminant function (DF) involving lipid and apoprotein indices of the plasma lipid system: DF = [apo B] X 0.03-[HDL cholesterol] X 0.04-0.81. DF greater than or equal to 0 discriminates from the controls 32% of the offsprings from the fathers with a history, DF less than 0 correctly classifies 98% of adolescents from the controls. The adolescents who have DF greater than or equal to 0 amounted to about 19% in representative samples of Moscow adolescents. Moreover, DF with 80% probability makes it possible to predict the time course of serum lipid levels in adolescents within 2 years. PMID- 2593470 TI - [Nutrition characteristics and the incidence of dyslipoproteinemia and ischemic heart disease among the population of the Buryat ASSR]. AB - The paper presents the data on dietary habits, blood lipid composition, and prevalence of coronary heart disease in native and non-native populations from Buryatia. They were obtained by using epidemiological (assessment of amounts of the food ingredients consumed) and biochemical (measurement of blood levels of total cholesterol, triglycerides, and high density lipoprotein cholesterol) methods. Differences were demonstrated in dietary habits between the native and non-native populations from Buryatia. The differences were shown to be associated with the prevalence of dyslipoproteinemias and coronary heart disease in these population groups. PMID- 2593471 TI - [Comparative characteristics of the incidence of ischemic heart disease and its risk factors among men and women aged 20-69 years (epidemiological study)]. AB - The study was undertaken to examine a random representative sample from the nonorganized male and female population from on of the Moscow districts. The survey covered 1238 males and 1241 females; the response-rate was 71% and 74%, respectively. Routine epidemiological tools and consistent criteria for their assessment were applied to the survey of the population. The authors examined the following risk factors: arterial hypertension, hypercholesterolemia, hypertriglyceridemia, hypoalphacholesterolemia, and cigarette smoking in relation to a particular CHD: acute myocardial infarction, heart failure, etc. PMID- 2593472 TI - [Quality of life of patients with hypertension]. AB - Diagnostic feasibilities of the methods for assessing the quality of life were studied in 260 patients with essential hypertension and 94 patients with a history of myocardial infarction. The reasons for lowering the quality of life were shown to be different in these groups in question. The life quality was found to be associated with the data of the psychological examination and indicators of the working capacity of patients with essential hypertension. PMID- 2593473 TI - [Functional state of the sinoatrial node in patients with intraventricular block]. AB - The function of sinus node (SN) was studied in 101 subjects with intraventricular blocks (IVB) and 30 controls. The patients with IVB showed a significant increase in the corrected time of SN function recovery and that of sinoatrial conduction both before and after medicamentous++ autonomic block, as compared to the controls. In general, signs of SN dysfunction were detected in 47 (46.5%) subjects with IVB. In 18.8% of the examinees, SN dysfunction was due to abnormal autonomic exposures, 27.7% had abnormalities in SN proper or perinodal tissue. ++Tachy-bradycardia was found in 53.5% patients with the sick sinus syndrome and IVB, 25% had concurrent atrioventricular conduction disturbances. A concomitant SN lesion was common in patients with IVB. One should take into account a type of this syndrome and the status of atrioventricular conduction when the optimal conditions of continuous electrical cardiostimulation are applied to patients with IVB and clinical signs of the sick sinus syndrome. PMID- 2593474 TI - [Functional status of the endocrine system in patients with hypertrophic cardiomyopathy]. AB - The study was undertaken to examine 27 patients aged 20 to 50 years who had hypertrophic cardiomyopathy (HC). Group 1 consisted of 12 patients with asymmetric cardiomyopathy. Group 2 comprised 15 with symmetric cardiomyopathy. Blood samples were taken from the cubital vein before and 30 and 60 minutes after administration of 0.2 mg thyroid-releasing hormone (TRH). Blood hormone concentrations were measured by radioimmunoassay. TRH test was found to provide an essential information on the function of the hypothalamo-hypophyseal-thyroid and hypothalamohypophyseal-adrenal systems in HC patients. The HC patients showed lower function of the hypothalamo-hypophyseal-adrenal system. There was a decrease in serum testosterone during all the periods of examination. At the same time the patients from Groups 1 and 2 had substantial features of the function of various links of the immune system, which may suggest a variance in the pathogenesis of the two types of the disease. PMID- 2593475 TI - [Intracardiac hemodynamics in middle-aged and elderly persons (data of echocardiographic study)]. AB - In terms of parameters for left ventricular diastolic filling, age-related hemodynamic characteristics were examined in elderly and senile subjects (aged 50 79 years). The echocardiographic parameters for left ventricular contractile and pumping functions and diastolic filling were found to undergo age-specific changes. The 7th decade of human life is largely different from the prior and subsequent decades in some echocardiographic parameters, in particular lower rapid filling fraction and higher slow filling fraction which may suggest the subjects of this age show initial manifestations of impaired myocardial relaxation. PMID- 2593476 TI - [Rupture of congenital aneurysm of the sinus of Valsalva (clinical aspects and diagnosis)]. PMID- 2593477 TI - [Interaction of thrombocytes with immobilized collagen in the vascular wall (a model for step-by-step study of formation of parietal thrombi)]. AB - Scanning electron microscopy was used to examine the interaction of platelets with types I, III, IV, and V human collagens (CI, CIII, CIV, and CV substrates) immobilized on the surface of cultural plates. Basic differences were found in the activity of collagen substrates against platelets. On the CV substrate, virtually all the adhesive platelets were in a non-spreading++ state, i.e. at the stage of initial attachment to the spread. The CIV substrate showed initial attachment, spreading, and attachment of platelets from the suspension to the spread platelets. In addition to the processes occurring at the CIV substrate, the CI and CIII substrates produced multilayer platelet aggregates on the strata of spreading platelets (thromboid aggregates). The surfaces covered with various types of collagens are an adequate model for quantitative step-by-step study of the formation of parietal thrombocytic thrombi and of mechanisms of this process control. PMID- 2593478 TI - [Changes in lipid peroxidation and the antioxidative system of the myocardium in adrenaline-induced damage of the heart]. AB - Epinephrine-induced cardiac injury (ECI) was simulated in rabbits. The indices of the system of peroxidation of lipids (LPO) and antioxidants were examined during various periods (3 hours, 3 and 9 days) of ECI. It was found that lower lipid antioxidative activity of blood, i.e. weaker body's antiperoxide protection, was found most early, then there was higher malonic dialdehyde (MDA) (a marker of thromboxane, TBA2) generation. The increase in antiperoxidase protection occurred at the level of the target organ (heart). There was a rise in the activity of the antioxidative enzyme superoxide dismutase and inhibited formation of primary products of LPO such as dien conjugates from early to 9 hours of the observation. When the natural antioxidant alpha-tocopherol was given prior to ECI, it prevented enhanced MDA formation in the platelets, optimized prostacyclin synthesis in the vascular wall, and stabilized blood lipid antioxidative activity. PMID- 2593479 TI - [Use of a synthetic opioid for the reversal of stress-induced damage of the myocardium and gastric mucosa in severe thermal trauma]. AB - Three series of experiments were performed in Wistar male rats. The first series covered the study of the function of isolated perfused hearts and the status of the gastric mucosa in intact animals. In series II and III, Stages IIIB-IV contact burn of 25% body surface was induced by a special device. The animals were observed for 24 hours. Following 23.5 hours of burn, the rats were injected placebo (Series II) or the synthetic Leu-enkephalin analogue dalargin, 10 micrograms/kg in the same amounts as placebo (Series III). After observation, the animals' hearts and stomachs were isolated and explored. In Series II, there was a considerable decrease in all the indices of cardiac function as compared to the controls, the ulcer index that characterizes the severity of stress-induced gastric mucosa injury was found to be 8.2. In Series III, the indices of cardiac function were even substantially higher than those in intact animals, the ulcer index was reduced to 0.01. Thus, dalargin, a Soviet synthetic Leu-enkephalin analogue, possesses marked anti-stress and cardioprotective effects in severe thermal trauma. The paper also considers the likely mechanisms responsible for the phenomena observed. PMID- 2593480 TI - [Changes in blood circulation in the post-resuscitation period of acute myocardial infarction]. AB - Cardiac output and parameters of myocardial contractility in the post resuscitation++ period of acute coronarogenic infarction were studied in experiments on dogs anesthetized with nembutal (40 mg/kg) (29 dogs). Twelve dogs reanimated after fibrillation-induced cardiac arrest were used as controls. The duration of clinical death was 5 minutes. The experimental animals showed a phase pattern of changes with initial hyperperfusion that was less pronounced in infarction and with subsequent one that was more profound than did the controls. A greater degree of +blood circulation disturbances were shown to be associated with high postresuscitation death rates. Diminished cardiac output is originally related to inhibited myocardial contractility; subsequently, of great importance are hypovolemia and arrhythmias. PMID- 2593481 TI - [Oxidation of I-131-middle-chain omega fatty acids in the heart in myocarditis of different etiologies]. PMID- 2593483 TI - [Clinical value of determining the activity of elastase- and chymotrypsin-like proteinases in the plasma of patients with nonspecific aortoarteritis and arteriosclerosis]. PMID- 2593482 TI - [Relation between the systemic fibrinolytic status and coronary reperfusion during thrombolytic therapy with streptokinase of patients with acute myocardial infarction]. PMID- 2593484 TI - [Evaluation of the effectiveness of cardiac glycosides in patients with implanted cardiac stimulators]. PMID- 2593486 TI - Cotransport mechanisms in renal tubules. PMID- 2593485 TI - [Characteristics of central hemodynamics in patients with hereditary hemochromatosis with cardiac lesions]. PMID- 2593487 TI - GFR increases before renal mass or ODC activity increase in rats fed high protein diets. AB - Consumption of a high protein diet causes renal hypertrophy and increased glomerular filtration rate (GFR). To determine the relationship between increases in GFR, renal ornithine decarboxylase activity (ODC), arginase activity, and renal growth, dietary protein intake was increased from 8.5% to 40% in 50 male Sprague-Dawley rats (HP). Forty-one rats remained on 8.5% protein as time controls (LP). Eight to 17 animals were killed daily for measurement of kidney weight (kidney wt), ODC and arginase activities, total kidney protein and DNA content. GFR increased within the first 24 hours after the increase in dietary protein and reached a maximum within 48 hours, ODC increased from 9.7 +/- 0.8 U/g to a peak of 170 +/- 35 U/g at 48 hours, decreasing to a stable value of 28.6 +/- 8.0 U/g at 72 hours and 25.4 +/- 5.1 U/g at 168 hours, a value significantly greater than that at time zero. Arginase activity did not change. Kidney wt as percent body weight (body wt) increased after the initial increase in both GFR and in ODC activity. The peak in ODC activity corresponded with the maximum increase in GFR and preceded the increase in renal mass. After GFR stabilized, ODC activity decreased to a plateau and renal growth relative to body wt ceased. The increase in kidney weight was accompanied by a parallel increase in total kidney protein. Kidney protein/kidney DNA ratio increased significantly by 96 hours, indicating that renal hypertrophy had occurred. The sequence of these events suggests that increasing GFR may trigger the rise in ODC activity. PMID- 2593488 TI - Effect of thromboxane inhibition on tubuloglomerular feedback in hydronephrotic kidneys. AB - The tubuloglomerular feedback (TGF) system is less sensitive after extracellular volume expansion (VE). In rats with partial ureteral obstruction, however, we have previously found increased TGF sensitivity during such expansion. Thromboxane A2 (TXA2) has been reported to be increased in the hydronephrotic kidney, and the present study was undertaken to investigate whether TXA2 might be responsible for these findings. The TGF characteristics were studied, by means of the stop-flow technique, in control and hydronephrotic rats before and after intravenous injection of either a thromboxane synthetase inhibitor or a thromboxane receptor antagonist during hydropenia. After VE, TGF was studied again. Proximal tubular stop-flow pressure (Psf) was measured during perfusion of the loop of Henle with a modified Ringer's solution, the maximal response (delta Psf) to an increased tubular flow rate was determined and the tubular perfusion rate which elicited a half-maximal decrease in Psf, designated the turning point, was recorded. In hydropenic control or hydronephrotic animals, TXA2 did not permanently change the TGF characteristics. During VE of the TXA2-blocked hydronephrotic animals, blocked both with synthetase inhibitor or receptor antagonist, TGF was reset to a lower sensitivity like VE controls, as indicated by a high turning point and a low delta Psf. It was therefore concluded that thromboxane A2 inhibition does not influence the TGF system in hydropenia, but that the production of thromboxane A2 is responsible for the resetting of the TGF system during VE in hydronephrotic animals. PMID- 2593489 TI - Effects of verapamil on the abnormalities in fatty acid oxidation of myocardium. AB - The oxidation of long (LCFA) and short chain fatty acids (SCFA) by myocardial mitochondria is impaired in CRF due to reduced activity of carnitine palmitoyl transferase (CPT) and of enzymes in the beta-oxidation sequence in mitochondrial matrix. It was proposed that PTH, through its ability to augment entry of calcium into cells, enhances calcium uptake by the myocardium leading to calcium accumulation which in turn affects mitochondrial function. A calcium channel blocker may therefore correct these derangements. The present study examined the effects of verapamil on LCFA and SCFA oxidation and on CPT activity of myocardial mitochondria and on 45Ca uptake by, and calcium content of, myocardium obtained from CRF rats and rats treated with PTH, with and without administration of verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in the oxidation of LCFA and SCFA by and of CPT activity of myocardial mitochondria and a significant increase in 45Ca uptake by, and content of, the myocardium. Simultaneous administration of verapamil reversed all these derangements. Administration of verapamil alone to normal rats for 4 or 21 days did not cause significant changes in these parameters. The results of our studies are consistent with the notion that the alterations in myocardial oxidation of LCFA and SCFA in CRF or after PTH treatment are related to PTH-induced calcium accumulation in the heart, and could be reversed by a calcium channel blocker. The data could provide a rational therapeutic approach for the management of uremic myocardiopathy. PMID- 2593490 TI - Effects of pentoxifylline in experimental acute renal failure. AB - The beneficial effects of post-insult administration of pentoxifylline, a novel hemorheologic agent experimentally studied in various ischemic diseases, were evaluated in two models of acute renal failure (ARF): direct nephrotoxicity (mercuric chloride 4 mg/kg via femoral vein) and hemoglobinuria (glycerol 10 ml/kg i.m.). Glomerular filtration rate (GFR) was estimated at baseline and following drug administration by creatinine clearances; tubular function was assessed by renal fractional and absolute electrolyte excretions. The incidence of mortality was decreased with a single dose of pentoxifylline 45 mg/kg (21.4%) compared to control rats (71.4%) 48 hours following induction of ARF with mercuric chloride. Although GFR and renal electrolyte excretion were significantly greater in rats given pentoxifylline compared to saline, the magnitude of difference was minimal. A return to baseline GFR was observed in the glycerol group administered a single i.p. dose of pentoxifylline 45 mg/kg (100.8 +/- 54.8%) compared to saline controls (45.6 +/- 22.7%; P less than 0.05). No differences in renal electrolyte excretion or mortality were observed in this model. Taken together, these data suggest that pentoxifylline, administered shortly after the initiation of ARF, exerts an ameliorative effect on the course and mortality of experimental ARF. The mechanism of amelioration most likely involves the stimulation of renal vasodilator prostaglandins as well as prevention of vascular congestion. PMID- 2593491 TI - Plasma insulin-like growth factors and bone formation in uremic hyperparathyroidism. AB - Bone formation in uremia is considered to be regulated in part by parathyroid hormone (PTH). However, while low levels of immunoreactive PTH are usually associated with low rates of bone formation in uremia, elevated PTH levels do not always correlate with increased bone formation. In an attempt to identify other factors that may regulate bone formation in uremic patients, we measured plasma immunoreactive insulin-like growth factors (IGF-I and IGF-II) in 15 patients who did not have aluminum-associated reductions in bone formation. Plasma levels of IGF-I but not PTH, were significantly higher in patients with high rates of bone formation when compared to patients with low or normal bone formation (P less than 0.02). While the bone formation rate at the tissue level correlated significantly with plasma PTH (r = 0.53, P less than 0.05) and IGF-I (r = 0.67, P less than 0.01), only for plasma IGF-I were there significant correlations with bone apposition (r = 0.57, P less than 0.05) and bone formation rate at the BMU level (r = 0.62, P less than 0.02), parameters which reflect mineralization activity at the cellular level. Among the static histologic parameters, osteoblastic osteoid correlated only with plasma PTH (r = 0.76, P less than 0.001), while osteoclast number correlated with both PTH (r = 0.56, P less than 0.05) and IGF-I (r = 0.67, P less than 0.01). There were no correlations between IGF-II levels and bone histology. From these data we suggest that IGF-I may promote bone formation in uremic patients with hyperparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593492 TI - Severe dialyzer dysfunction undetectable by standard reprocessing validation tests. AB - It is generally accepted that careful monitoring of total cell volume and ultrafiltration rates will ensure adequate function of reprocessed dialyzers. During routine urea kinetic measurements we noted that the percent of patients with clearances less than 200 ml/min increased from 5% to 48% despite adherence to these validation tests. As these patients did not have evidence of recirculation in the vascular access, possible causes of dialyzer dysfunction were investigated. Injection of methylene blue into the dialysate port revealed non-uniform flow of dialysate in dialyzers from patients with markedly reduced clearances. In vitro studies of dialyzers subjected to sequential daily reprocessing, without patient exposure, demonstrated that in vitro clearances declined in one lot but not another. The initial clearances of 218 +/- 4 ml/min fell progressively to 112 +/- 18 (P less than 0.001) after 15 reuses. No effects of reprocessing were found in a different lot (230 +/- 2 vs. 226 +/- 4 ml/min). Soaking the dialyzers from the affected lot in either the disinfectant or dialysate solution caused a decline in the clearances which was less than that of serial reuse. Although the magnitude of the problem of dialyzer malfunction with reuse is unknown, careful attention to dialyzer function is warranted in patients treated with reprocessed dialyzers. PMID- 2593493 TI - Donor specific transfusions or cyclosporine for related-donor kidney transplantation? AB - DST and cyclosporine are two immunosuppressive strategies to improve first year graft survival in high MLC, one-haplotype matched, living-related donor kidney transplantation. However, each has disadvantages: The conventional strategy of DST may sensitize the recipient to donor antigens, precluding transplantation from that donor, and cyclosporine may increase graft failure due to nephrotoxicity. We used decision analysis to compare these two strategies. We assumed that the risk of sensitization by DST is 12%, that graft failure in the first year is equal in both strategies, but that the annual probability of graft failure in later years is 2.6% with DST and from 2.7% to 3.6% with cyclosporine. Patients sensitized by DST and patients with graft failure undergo dialysis while awaiting cadaveric donor transplantation using cyclosporine. Outcomes were assessed as quality-adjusted years of survival. The analysis was deliberately biased to favor DST, the conventional strategy. Quality-adjusted life expectancy for a 40-year-old patient in both strategies is from 17.7 to 19.1 years. The difference between the DST and cyclosporine strategies ranges from -0.7 to +0.6 years. Given current data on sensitization by DST, long-term cyclosporine nephrotoxicity, and deliberate biases favoring the DST strategy, we conclude that there is no substantive advantage of the DST strategy. Cyclosporine is equally efficacious for recipients of high MLC, one-haplotype matched kidney transplants, and may be preferred for transplants from more distant relatives and unrelated living donors. PMID- 2593495 TI - 35th scientific meeting of the Dutch Society of Nephrology. The Hague, The Netherlands, February 25, 1989. Abstracts. PMID- 2593494 TI - Cellular biology of the water channel. PMID- 2593496 TI - [The use of SKN carbon enterosorbents in the combined treatment of patients with obstructive jaundice. III. The results of clinical research]. AB - The use of SKN P-1 and SKN P-2 carbonic enterosorbents in the complex treatment of the patients contributed to decrease in pronouncement of cholemic intoxication. A method is easy, noninvasive, its use is recommended in patients, the elderly and senile in particular, with obstructive jaundice. PMID- 2593497 TI - [Principles of the diagnosis and surgical treatment of internal biliary fistulae]. AB - On the basis of examination of 58 patients, the main principles of diagnosis and surgical treatment of the internal biliary fistulas are suggested. PMID- 2593498 TI - [A diagnostic algorithm in the postcholecystectomy syndrome]. AB - The diagnostic informative value (according to the "sensitivity" and "specificity" tests) of the findings of clinical, laboratory, biochemical (CI, LI, BI), and adjuvant methods of investigation in 74 patients with postcholecystectomy syndrome (PCES), who underwent reoperations, was established. The open to general use diagnostic algorithm of PCES was determined. CI, LI, BI are preliminary screening tests. The use of adjuvant methods, their sequence and combination depend on the character of the diagnostic information obtained. PMID- 2593499 TI - [Suppuration of the postcholecystectomy wound]. AB - In 212 patients after elective cholecystectomy, the bacteriologic study was performed. Bile infection was revealed in 43 (20.3%) patients, wound suppuration- in 28. Of them in 20, pathogenic microflora was cultured. In 16 patients, the microorganism in the bile and wound were identical. Escherichia coli was the main microorganism cultured from the wound and bile. The incidence of wound suppuration after cholecystectomy with the common bile duct revision is higher than after cholecystectomy alone. Changes in the gallbladder function (excluded gallbladder), or cholangiography didn't increase the risk of wound suppuration. Microorganisms cultured from the bile were the most sensitive to gentamycin and cephalosporin. Prophylactic use of antibiotics for reduction of the incidence of wound suppuration is recommended. PMID- 2593500 TI - [The classification of a combination of cholelithiasis and urolithiasis]. AB - In 105 patients, the combination of bili- and urolithiasis was revealed. With the aim of improvement of early diagnosis of biliurolithiasis, the three clinical groups of patients were distinguished. In 60% of patients, metabolic obesity was noted. The authors suggest to extend the indications for combined and consecutive operations in patients with biliurolithiasis. PMID- 2593501 TI - [Changes in the architectonics of the bile ducts in inflammatory processes]. AB - A study of 156 preparations of the liver of adults, and as well examination of 62 patients has shown, that in inflammatory processes in the liver and bile ducts, the considerable changes in the length, diameter, angles of the confluence of the bile ducts occurred. With increase in the pronouncement of biliary hypertension, their diameter increases. PMID- 2593502 TI - [Secretory pressure of the liver and bile hydrodynamics in prolonged obstruction of the bile ducts]. AB - It is established in the experiment, that in stable obturation of the cystic and common bile ducts, the biliary pressure increases to the level of secretory hepatic pressure, at which it maintains for 9 days. Beginning from the day 10 of obturation, the common bile duct pressure sharply decreases (P less than 0.01) and remains decreased up to the end of investigation (day 27). The author distinguishes the periods of increase and stabilization of the pressure, stable hypertension, stable decrease of the pressure. The first two periods are indicative of compensation of the secretory function, the third one--of its decompensation. PMID- 2593503 TI - [The choice of suture material in forming bile-diverting anastomoses]. AB - In the experiment, it was established that the use of a synthetic thread of the noncapillary type with a small diameter, when microsurgical technique was employed, provided minimal damage, full-value adaptation of the membranes of the organs sutured, thus facilitating primary healing of anastomosis. PMID- 2593504 TI - [A method for preserving liver function in total short-term stoppage of the blood flow via the portal vein]. AB - In the experiment on 40 adult mongrel dogs, a method for detoxication of an organism with the use of hemosorption by means of the three-lumen catheter has been developed. The expediency to perform hemosorption in acute impairment of circulation in the portal venous system by the method of portocaval shunting with simultaneous liver perfusion has been proved. PMID- 2593505 TI - [Reportalization of the liver in subhepatic block of the portal vein]. AB - The possibility of liver reportalization in subhepatic blockade of the portal vein is substantiated experimentally. The operation of liver reportalization was performed in 2 patients with good long-term results. PMID- 2593506 TI - [The importance of the NBT test in the prognosis and assessment of treatment efficacy in complicated forms of cholelithiasis]. AB - On the basis of examination of 34 patients, it was established that after the operations on the bile ducts in development of pancreonecrosis, peritonitis, purulent cholangitis, subhepatic abscess, suppuration of the postoperative wound, the indices of NBT test exceeded the norm 2 times and more. Significant decrease in the indices of NBT test--is a prognostic sign of the favourable postoperative course and effectiveness of the treatment performed. PMID- 2593508 TI - [Surgical treatment of acalculous cholecystitis]. AB - The results of surgical treatment of 91 patient with acalculous cholecystitis are analysed. The active surgical tactics is substantiated. It is shown that in thorough examination of a patient before and at the time of operation, correction of pathology of the gallbladder and bile ducts and other alimentary organs, it is possible to achieve good long-term results. A classification of acalculous cholecystitis is presented. PMID- 2593507 TI - [Diagnosis, surgical treatment procedure and results in acute cholecystitis in young patients]. AB - Among the patients with acute cholecystitis, those at the age of 20-45 years account for 12.6%. Of them, 50.9% develop complications: choledocholithiasis, obstructive jaundice, cholangitis, pancreatitis etc. The main method for treatment of the patients is the operation within 24-48 hr from the moment of their admission with intraoperative diagnosis of pathology of the extrahepatic bile ducts. There were no lethality, postoperative complications were noted in 9.3% of the patients. PMID- 2593509 TI - [Diagnosis and treatment of acute cholangitis]. AB - The results of surgical treatment of 114 patients with acute cholangitis were analysed. With the aim of early diagnosis, the sonography and direct contrasting of the bile ducts were used. The conservative treatment has proved to be effective in 64.9%. Bile ducts decompression before the operation was performed in 29 patients, its effectiveness was 89.6%. Overall lethality in acute cholangitis was 11.4%. PMID- 2593510 TI - [External drainage of the bile ducts via the stump of the cystic duct to prevent postoperative complications in elderly patients]. AB - Operated on were 165 elderly and 68 young patients for calculous cholecystitis complicated by choledocholithiasis and obstructive jaundice. Drainage through the cystic duct stump is the most effective method for external drainage of the common bile duct in operative interventions on the bile ducts in elderly patients, which permits to reduce considerably the incidence of postoperative complications. PMID- 2593511 TI - [Transduodenal papillosphincterotomy in the treatment of nontumorous lesions of the terminal portion of the common bile duct]. AB - For benign stricture, obstruction of the major duodenal papilla (MDP) and terminal common bile duct in 130 patients with acute and chronic cholecystitis and its complications, the papillosphincterotomy was performed. Postoperative lethality was 3.8%. A good long-term result was noted in 84% of the patients, satisfactory--in 12%, bad--in 4%. There were no restenosis of MDP and recurrent choledocholithiasis. PMID- 2593512 TI - [The role of a sympathetic pharmacologic blockade in restoring blood flow to the organ in acute cholecystitis]. AB - By means of a method of rheography, in 74 patients with acute cholecystitis before and after the operation, and in 26 healthy subjects as well, the blood flow of the brain, lungs, liver and lower extremities under conditions of the use of benzohexamethonium, obsidan, aminazine and neostigmine methylsulfate was studied. Resulting from the use of sympathetic pharmacologic blockade, already by day 2, the indices of cerebral, pulmonary and hepatic blood flow normalized or exceeded the normal level. PMID- 2593513 TI - [The complex diagnosis of high obstruction of the bile ducts]. AB - On the basis of the results of examination of 275 patients with high obstruction of the bile ducts of different genesis, it is shown, that ultrasound diagnosis permits correct establishment of the nature of jaundice in 96%, level of obstruction in 75.8% of cases. In use of combination of the direct methods of ante- and retrograde cholangiography and sonography, the precise diagnosis permits to determine the possible volume of operative intervention. PMID- 2593515 TI - [Iatrogenic injuries to the bile ducts]. PMID- 2593514 TI - [The early rehabilitation of patients with surgically treated calculous cholecystitis]. PMID- 2593516 TI - [Surgical treatment of intraoperative injuries of the bile ducts]. PMID- 2593517 TI - [Drug-induced hepatitis following levorin treatment simulating obstructive jaundice]. PMID- 2593518 TI - [Cholelithiasis as a risk factor for the occurrence of gallbladder cancer]. PMID- 2593519 TI - [2-stage splenic rupture]. PMID- 2593520 TI - [A case of the combination of cholelithiasis and urolithiasis in a patient with Lobstein's syndrome]. PMID- 2593521 TI - [A rare anomaly of the extrahepatic bile ducts]. PMID- 2593522 TI - [A case of common bile duct cyst]. PMID- 2593523 TI - [Gastrointestinal hemorrhage as a complication of a spontaneous internal biliary fistula]. PMID- 2593524 TI - [Multiple biliodigestive fistulae]. PMID- 2593525 TI - [Acute obstruction of the small intestine caused by gallstones]. PMID- 2593526 TI - [The passing of a large bile concretion after endoscopic papillosphincterotomy]. PMID- 2593527 TI - [Deep duodenobiliary reflux after supraduodenal choledochoduodenostomy]. PMID- 2593528 TI - [Disordered immunologic reactivity in patients with chronic calculous cholecystitis]. AB - In patients with chronic calculous cholecystitis, the number of T-lymphocytes decreased, the number of B-lymphocytes and their ability to transform into the blasts in response to stimulation of the specific bacterial antigen increased, the synthesis of immunoglobulins intensified, a titre of the antibodies specific to microflora of the biliary mucosa grew, the levels of complement, lysozyme and properdin decreased, the bacterial activity of blood serum was suppressed. It is necessary to correct these disorders in the process of preoperative preparation of the patients. PMID- 2593529 TI - [The treatment of cholangiogenic liver abscesses by the use of hemosorption and extracorporeal membrane oxygenation]. PMID- 2593530 TI - [Teratoma of the liver]. PMID- 2593531 TI - [The role of middle molecules in the occurrence of a hyperthermic reaction during the reinfusion of ascitic fluid in patients with liver cirrhosis]. PMID- 2593532 TI - [Aneurysm of the splenic artery as the cause of segmental extrahepatic portal hypertension]. PMID- 2593533 TI - [A modified method of cholecystectomy]. PMID- 2593535 TI - [A method for draining the common bile duct]. PMID- 2593534 TI - [A device for measuring the width of the common bile duct on cholangiograms]. PMID- 2593536 TI - [The indications and technic for performing a hepaticocholecystojejunostomy using a mechanical suture]. PMID- 2593537 TI - [A method of choledochojejunostomy]. PMID- 2593538 TI - [A method for the preoperative preparation of patients with complete external biliary fistulae]. PMID- 2593539 TI - [The determination of the leukocytic index of intoxication in cholecystitis]. PMID- 2593540 TI - [An approach to the posterior vagal trunk in performing a posterior truncal or a posterior selective vagotomy]. PMID- 2593541 TI - [Intraoperative determination of the borders of the functional sections of the stomach using the atropine test]. PMID- 2593542 TI - [A method for the complex study of secretion and blood flow in the stomach]. PMID- 2593543 TI - [A clamp with detachable arms]. PMID- 2593544 TI - [A new diagnostic sign of acute appendicitis in children]. PMID- 2593545 TI - [The prevention of complications in puncture catheterization of the subclavian vein in children]. PMID- 2593546 TI - [Surgical treatment procedures in patients with external and internal hepatobiliary fistulae]. AB - Within a period of from 1967 to 1987, the authors treated 389 patients with injuries and diseases of the liver, bile ducts, adjacent organs, which were complicated by long-existing external and internal fistulas of the bile ducts, or intrahepatic cavities. PMID- 2593547 TI - [Long-term results of truncal and selective proximal vagotomy with pyloroplasty]. AB - The work is based on the results of analysis of clinical material concerning patients who were treated by operation for duodenal ulcer 3-5 years earlier. Truncal vagotomy and pyloroplasty (TV + P) was performed in 166 and selective proximal vagotomy with pyloroplasty (SPV + P) in 195 patients. The authors found the long-term results to be similar in both groups and did not reveal any advantages of SPV + P over TV + P, in view of which they do not find it necessary in principle to decline from conducting TV + P at the present time. PMID- 2593548 TI - [Postoperative deformities of the stomach]. PMID- 2593549 TI - [Errors in dissection of the ligament of Treitz]. PMID- 2593550 TI - [Treatment of surgical complications of opisthorchiasis]. PMID- 2593551 TI - [Roentgeno-endobiliary prosthetics]. PMID- 2593552 TI - [Use of intestinal tubes with reinforced rings]. PMID- 2593553 TI - [Appendectomy in extension of inflammatory tissue infiltration to the cupula of cecum]. PMID- 2593554 TI - [Treatment of giant duodenal ulcers]. PMID- 2593555 TI - [Irrigated bandages]. PMID- 2593556 TI - [Needle for closing liver wounds with a dermal suture]. PMID- 2593557 TI - [Giant epithelioid leiomyoma of the stomach]. PMID- 2593558 TI - [Cancer of the dermal implant after plastic surgery of the esophagus using the small intestine]. PMID- 2593559 TI - [Tuberculosis of the stomach]. PMID- 2593560 TI - [Forced duodenectomy with subsequent transplantation of the major duodenal papilla to the jejunum during gastric resection]. PMID- 2593561 TI - [Torsion of the accessory spleen simulating acute appendicitis]. PMID- 2593562 TI - [Polyposis of the small intestine complicated by invaginated intestinal obstruction]. PMID- 2593563 TI - [A rare form of complicated internal hernia]. PMID- 2593564 TI - [Vagotomy in the treatment of penetrating duodenal ulcers]. PMID- 2593565 TI - [Vagotomy in the surgical treatment of pyloroduodenal ulcers]. AB - The results of organ-preserving operations in 243 patients with peptic ulcer of the pyloric part of the stomach and duodenum are analysed; 88% of patients were operated on in the occurrence of life-threatening complications of the disease. The main type of surgical operation was selective proximal vagotomy which was isolated only in 44 cases. The immediate and late sequela of the operations were evaluated by means of the aspiration-titration method of studying acid production, pH-metry, roentgenoscopy, electrogastrography, and esophagogastroscopy. The late results of the vagotomy were studied during prolonged continuous medical observation of the patients. A socioeconomic impact of SPV is shown. The results of organ-preserving operation were excellent in 84.4%, satisfactory in 10.5%, and poor in 5.1% of patients according to Visick's classification. PMID- 2593566 TI - [Prevention and complex treatment of duodenal stump incompetence]. AB - The results of surgical treatment of 1,069 patients for gastric and duodenal ulcer were studied. Duodenal stump incompetence (DSI) developed in 25 patients (6.3%) after the Billroth II operation; the incompetence was manifested by three clinical forms: infiltrative, primary-fistular, and perforative-peritoneal. Each form of DSI calls for specific tactics of treatment. The perforative-peritoneal form is most dangerous; during its operative management active aspiration perfusion drainage of the zone of the stump must be installed and the duodenum relieved of a load as much as possible. Drugs reducing pancreatic function, postural drainage, and a diet is included in the complex of therapeutic measures in DSI. The wide introduction of organ-preserving operations into surgical practice will make it possible to avoid this threatening complication. PMID- 2593567 TI - [Diagnosis and treatment of recurrences of peptic ulcer after selective proximal vagotomy]. AB - Selective proximal vagotomy (SPV) was performed in 658 patients. Recurrent ulcer was revealed in 6.2% of them. A classification of recurrent peptic ulcer is proposed. An operation was carried out for a second time in 65 patients. Correct techniques of SPV, excision of the ulcer, and stomach draining operations with consideration for the functional condition of the duodenum during the first operation are conducive to marked decrease in recurrences of the ulcerative process. PMID- 2593568 TI - [Clinical features and surgical treatment of postbulbar ulcers of the duodenum]. AB - Experience in the treatment of 1,087 patients with postbulbar duodenal ulcers is discussed. Complications were found in 1,014 of them; penetration occurred in 707 patients, in combination with stenosis in 247, with hemorrhage in 251, and with both of these complications in 11 patients. In 139 patients the only complication was acute bleeding, in 38, stenosis, and in 30 patients, perforation. Operative treatment was carried out in 1,075 patients; resection of the stomach for exclusion was conducted in 458, selective proximal vagotomy in 24, closure of the perforated ulcer in 13, and stitching of the bleeding vessel with Heineke Mikulicz pyloroplasty in 18 patients. The mortality was 2.6%. Study of the late results in follow-up periods of 2 to 35 years showed good results in 90.8% of cases. PMID- 2593570 TI - [State of the valvular function of the cardia in patients with duodenal ulcer before and after vagotomy and methods of its correction]. AB - The authors studied the valvular function of the cardia in 714 patients who were kept under regular medical observation and in 138 patients who had been operated on for duodenal ulcer. Changes were found in the cardia of 9.4% of patients who underwent regular medical examination and in 17% of these subjected to operation. The valvular function of the cardia was impaired after vagotomy in all cases. Fundoesophagocrurorhaphy is the best method for correction of cardiac dysfunction. PMID- 2593569 TI - [Surgical tactics in ulcerous pyloroduodenal stenosis]. AB - The authors generalize their experience in the treatment of 528 patients with ulcerous pyloroduodenal stenosis, who accounted for 19.3% of all patients who were operated on and for 29.8% of those with complicated forms of peptic ulcer. All the patients underwent operation after brief (2-3 days) replacement of hydrogen ion deficiencies. Resection of the stomach was carried out in 418 patients, organ-preserving operations-in 102, gastroenteroanastomosis-in 8 patients. Total mortality was 2.5%. There were no fatal outcomes in organ preserving operations. The incidence of postoperative gastric atony was 6.1% after organ-preserving operations and 4.9% after resection of the stomach. PMID- 2593571 TI - [Treatment of patients with gastrogenic tetany]. AB - The article analyses the results of combined treatment of 22 patients with duodenal ulcer complicated by cicatricial-ulcerative obstruction of the pylorus, gastrogenic tetany. Within 9-11 days of intensive therapy, the disorders of homeostasis were stopped and operation was performed for restoring the passage of food. Combined treatment reduced the mortality from 30 to 13% among this category of patients. PMID- 2593573 TI - [Questions of tactics and choice of surgery in gastroduodenal hemorrhage]. AB - The authors analysed 368 clinical cases with gastroduodenal hemorrhages. The changes in blood microcirculation and nonspecific immunity were studied in 62 patients. They proposed a method of complex nonoperative treatment of gastrointestinal hemorrhages, including ganglionic block, which made it possible not only to reduce the operative activity but also to achieve epithelialization of ulcers in patients with peptic ulcer. As the result of the study, a unique classification of the severity of blood loss is suggested which is based on the degree of deviation off the tests studied from the normal values. If gastroduodenal hemorrhage continues, an operation is recommended, the character of which is determined by the patient's age, the severity of blood loss, and the source of bleeding and its localization. PMID- 2593574 TI - [Hydrostatic pressure in the duodenum during the immediate postoperative period after resection of the stomach]. AB - Twenty-nine patients were examined after resection of the stomach by various methods. The hydrostatic pressure value was found to be independent on the method of resection. It was maximum on the third postoperative day in all patients. No correlation was established between the hydrostatic pressure and the amount of duodenal contents discharged along the nasoduodenal catheter. PMID- 2593572 TI - [Intraoperative pH-metry in the prevention of incomplete vagotomy and ischemia of the gastric wall in selective proximal vagotomy]. AB - Experiments were conducted on 14 mongrel dogs to appraise the validity of the results of intraoperative pH-metry in the control of vagotomy completeness depending on the force of pressure exerted on the pH electrode with consideration for the type of a pH catheter used. The level of parietal pH increased with elevating pressure force due to diminished circulation in the gastric wall. The encountered diminution of circulation in the gastric wall after SPV increases still more the pH level and reduces the amplitude of its growth even in areas with maintained parasympathetic innervation with the use of histamine, which raises the probability of incomplete vagotomy. The authors conclude that pH-metry by slight application of the pH electrode to the gastric wall raises the validity of the values recorded and reduces the frequency of incomplete vagotomy in patients operated on in the clinic by 4.7 times. Increase of parietal pH to more than 6.7, irrespective of the force of the exerted pressure, is an indirect sign of ischemia of the gastric wall. PMID- 2593575 TI - [Combined gastrectomy in cancer]. PMID- 2593576 TI - [Results of the local endoscopic treatment of chemical burns of the esophagus using medical glues]. AB - The results of treatment of chemical burns of the esophagus in 140 patients with the medical glues MK-8 and MK-14E. Application of the glues was undertaken in the presence or absence of hormone therapy. The method of glue application is described. The use of the method reduces the time of healing of the destructive lesions of the esophageal mucosa in chemical burns and facilitates the prevention of complications. PMID- 2593577 TI - [Combined operations in cholelithiasis]. AB - Experience in combined operations for cholelithiasis on 162 patients is discussed. In 98 patients, cholecystectomy was performed as a simultaneous stage of surgical treatment, the main stage of the operation was gastrectomy or resection of the stomach for cancer in 26 patients, formation of a small stomach for alimentary-constitutional obesity in 19, various types of vagotomy in 33, hemicolectomy, resection of the colon and sigmoid intestine for malignant tumors in 10, and reconstructive manipulations on the stomach, correction of intestinal obstruction, and other operations in 10 patients. Cholecystectomy was the main stage of the operation in 48 patients with hernias, benign tumors of the uterine appendages, breasts, and soft tissues. The authors insist that cholecystectomy must be carried out when cholelithiasis is a concurrent disease; they showed that increase in the extent of the operative intervention had no essential effect on mortality and frequency of postoperative complications (mortality rate, 1.2%). The authors substantiate the expediency of performing combined operations from economical considerations--the economical effect of the operations conducted by the authors came to some 51,000 roubles. PMID- 2593579 TI - [Use of CO2 laser in the treatment of suppurative-necrotic lesions of the foot in patients with diabetes mellitus]. AB - The CO2 laser Skalpel-I was used in the treatment of pyonecrotic lesions of the foot in 57 patients with diabetes mellitus. Preliminary comparison of the results shows the method to be promising: the number of high amputations reduced from 34% to 19%, the mortality, from 17% to 6%. The authors conclude that introduction of laser techniques into clinical practice will lead to a decrease in the number of high amputations and will improve further rehabilitation of patients with diabetes mellitus and pyonecrotic complications in the lower limbs. PMID- 2593578 TI - [Experience in the use of laser instruments in surgery of the anorectal region]. AB - The article discusses experience in surgical treatment of 480 patients with the most common diseases of the anorectal region (acute and chronic haemorrhoids, acute and chronic paraproctitis, polyps, chronic fissures of the anal canal) in which special laser tools were used. The carbonic acid laser Skalpel-1 with a wave length of 10.6 microns and power of 30 W was used as the source of laser radiation. Methods of operations with the use of these tools are described in detail. The advantages of laser instruments in the treatment of patients with the above listed diseases are shown on a rich clinical material. PMID- 2593580 TI - [Reconstructive surgery in patients with nonspecific ulcerative colitis and Crohn disease]. AB - The article analyses experience in reconstructive operations on 89 patients with unspecific ulcerative colitis and Crohn's disease in the period from 1960 to 1987. Most frequently, surgical rehabilitation of these patients proved to be possible when the time between the onset of the disease and the primary operation was no more than 3 years. Special selection of patients for reconstructive operations does not exclude those with complications in the anorectal region, the manifestations of which should be, however, minimal. The inflammatory process in the rectum should not exceed the first degree of activity. The most favourable periods for reconstructive operations are 6 to 12 months after removal of the colon. The best results were achieved in patients with ileorectal and a low ileosigmoid anastomosis which were created in 90% of patients with unspecific ulcerative colitis and in 41% of those with Crohn's disease. PMID- 2593581 TI - [Surgical treatment of Meckel's diverticulum]. AB - The author analysed the results of operations on 19 patients with emergency diseases of the abdominal organs caused by pathological processes in Meckel's diverticulum. The inflammatory process in the diverticulum led to acute obstruction of the small intestine in 12, acute diverticulitis in 5, and peptic ulcer complicated by perforation of the intestinal wall in 2 patients. Two patients died in the postoperative period from progressing peritonitis. It was established that Meckel's diverticulum may occur in any area of the small intestine. Meckel's diverticulum detected during planned laparotomy must be resected. PMID- 2593582 TI - [Programmed laparotomy in the diagnosis and therapy of pathology of the abdominal cavity]. AB - The authors analyse the performance of programmed laparotomy for dynamic visual observation over the condition of the abdominal organs in 3 patients when (as they claimed) laparoscopy would have produced no effect. The article reports on the efficacy of programmed laparotomy conducted by the method suggested by the authors in 15 patients with purulent peritonitis for repeated cleansing of the abdominal cavity. PMID- 2593583 TI - [Use of autologous dermal implants in surgery]. AB - Autogenous dermal implants were used for plastic purposes in 359 patients who underwent operations for inguinal, postoperative, and diaphragmatic hernias, closure of laparotomy wounds and fixation of sutures on the esophagus. Suppuration of wounds occurred in 2% of cases. Recurrences were noted in 1.8% in treatment of inguinal hernias and in 2.9% of patients treated for postoperative hernias. There were no eventrations. Morphological examination showed autogenous dermal tissues to possess good properties as plastic material. PMID- 2593584 TI - [Clinico-anatomical evaluation of donor kidneys unsuitable for transplantation]. AB - The authors conducted clinicoanatomical analysis of 112 donor kidneys which clinicians found to be unfit for transplantation. The procedure of preparing the donors in these cases did not differ from that commonly accepted. An essential moment was prolonged arterial hypotension (6.0 +/- 0.8 hours), in donors whose kidneys were used for transplantation it lasted 2.0 +/- 0.2 hours. Examination showed that in 90% of cases the kidneys were unfit because of congenital or acquired diseases. It is concluded that the existing clinical methods for appraising the fitness of donor kidneys are adequate. PMID- 2593585 TI - [Principles and technics of inguinal herniotomy]. AB - The causes of recurrences after operation for inguinal hernia are discussed, on basis of which the principles and techniques of inguinal herniotomy are substantiated. The article shows the results of operations in 1,734 patients with various types of inguinal hernia, 6.99% had a recurrence (4.6% of patients with simple oblique and 18.75 with complicated hernias). Hernioplasty by an external graft of the external oblique muscle of the abdomen, the techniques proposed by the author, produced the best results with recurrences encountered in an average of 2.29% of cases. PMID- 2593586 TI - [Results of the surgical treatment of perforated ulcer of the stomach and duodenum]. AB - The authors studied the results of operations for perforated gastric and duodenal ulcers performed from 1978 to 1987. During this period, 263 operations were carried out, the postoperative mortality was 11%. The late results were studied in 137 patients in follow-up periods of 12 months to 11 years. Decrease in the postoperative mortality rates depends on timely hospitalization of the patient and adequate performance of the operation. Closure of the ulcer with sutures is expedient in young patients who have no clinical manifestations of the disease (silent ulcer). In individuals with recurrent ulcers, the subsequent therapeutic policy must be more active, that is planned surgical treatment. PMID- 2593587 TI - [Prevention of complications in surgical treatment of inguinal and femoral hernias]. PMID- 2593588 TI - [Evaluation of the efficiency of the visual system in automobile drivers]. AB - On the basis of results of the examinations performed in 545 persons one was aiming to establish the most frequently encountered abnormalities which are the cause of disqualifications in obtaining a professional or unprofessional driving licence. The licence obtained 386 persons and from that number 59.1 per cent professional and 40.9 unprofessional drivers. One hundred and fifty nine persons were refused a driving licence; 66.6 p.c. of this number were professional and 38.4 p.c. unprofessional drivers. The ground for disqualification referred to the presence of squint - 40.9 p.c., low visual acuity - 29.4 p.c., disturbances in color discrimination - 8.2 p.c., and three-dimensional vision - 4.4 p.c. PMID- 2593590 TI - [Ophthalmologic problems and occupational fitness]. AB - The authors point out the tests which enable the evaluation of the binocular vision in examinations qualifying for an employment in the railway service. The employees with an open angle glaucoma may continue their work under condition of controlling their visual functions in 3-months intervals. In cases of a macular degeneration examination of mesopic vision is necessary. PMID- 2593589 TI - [Protective sunglasses and color discriminating ability]. AB - The influence on color vision of 4 kinds of sun-glasses with various characteristics of transparency and absorption of 25, 50, 75 p.c. was evaluated. Sixty persons with normal color discrimination took part in investigation. The selection of filters for professional drivers and railway engine-drivers was performed on the basis of Nagel's anomaloscope and Farnworth-Munsell's 100--Hue tests. PMID- 2593592 TI - [Corneal sensitivity in workers in contact with petroleum products]. AB - Evaluation of the corneal sensitivity was carried out in 251 workers who have had a direct contact with petrol and its derivates and in 45 persons of a control group. It was established that the corneal sensitivity--especially in its central region--was distinctly lowered in persons employed in the department of asphalt oxidation and cleaning of sewages. This concerned particularly the workers with a long-lasting, many years service. PMID- 2593591 TI - [Disorders of color vision in employees of the Masovian Refining and Petrochemical Industries in Plock]. AB - Attention is drawn to the problem of the influence of the petrol derivates on the frequency of acquired dyschromatopsia. It has been observed--on the basis of performed examinations of the color vision by means of the Farnsworth-Munsell's 100-Hue test--that the general numerical index of the faults is increasing proportionally to the period of employment, i.s. the period of the contact of the workers with the derivates of petrol. PMID- 2593593 TI - [Usefulness of selected psychophysical methods in the evaluation of lighting conditions]. AB - The author examined the frequency of blinking and the position of the near point influenced by practicing a work of considerable visual requirements in various conditions of illumination. It was established that a 7-hours work causes an increase in the frequency of blinking in all the examined persons and receding of the near point in 93 p.c. of subjects. Calculated was the coefficient of correlation and the tangent of the inclination angle of the extent of changes of the measured functions from the logarithm of intensity of the illumination on the work stand. The received coefficients of correlation were -0.08 in case of changes of the near point and -0.63 for the changes of blinking frequency; instead the tangent of inclination angle respectively -0.41 and -122. PMID- 2593594 TI - [Status of the visual system in operators causing railway accidents]. AB - One hundred and eighty four engine-drivers aged 21-60 years were examined; 91 from them provoked an accident not stopping the train in front of the "Stop" signal; 93 constituted a control group. Compared was the status of the visual system and the efficiency of the visual functions such as: binocular vision, color vision and asthenopia, mesopic vision and the sensitivity to glare. In engine-drivers of the "accident-prone" group one observed an increased sensitivity for glare. The authors suggest it would be necessary to introduce to the qualification examinations for engine-drivers the evaluation of the sensitivity to glare and of the visual ability in mesopic conditions. PMID- 2593595 TI - [Dynamics of visual hand localization in the 24-hour observation of persons working under conditions of additional loads]. AB - Examined--by means of a Starkiewicz's hand localizer--were 170 right-hand workers of a paper factory working in conditions of excessive noise and high temperature of the surroundings. Analyzed were 140 persons tested 4 times in the period of each production shift (6.00-14.00; 14.00-22.00, and 22.00-6.00). The analysis showed the maximal efficacy of the visual function of the hand localization in the range of the right-hand and in the course of the night shift in both age groups. PMID- 2593596 TI - [Reaction of Langerhans cells of the corneal epithelium to topically applied lead]. AB - Twenty guinea pigs were given a solution of lead acetate into the conjunctival sac. Ten animals from the control group received distilled water. In the contaminated group one observed conjunctival irritation and a paralimbal opacification of the cornea. Histopathological examination of the contaminated animals showed a distinctly lower number of the Langerhans' cells in comparison with the control group. PMID- 2593597 TI - [Chemical burns of the eyes. II. Surgical treatment]. AB - An analysis of surgical treatment of the consequences of eye burns in miners and the employees working on the surface of coal mines treated in the period 1978 1980. Discussed are the results of corneal grafting and keratoprosthesis in cases of severe corneal opacity. PMID- 2593599 TI - [Usefulness of the provocative prism test for studying visual hand localization]. AB - Two examples are presented of the behaviour of the visual-hand localization during examination by means of a hand localizer, each eye separately with a provocative prism test and without the prism. The provocative test allows to perform a deeper analysis of the changes of the hand localization. The authors describe the behaviour of the visual-hand localization in 40 examined persons and consider the amount of the localization recoil caused by placing of a prism, the speed of the straightening out the changed localization, in other words a hypercorrected sign of deviation and lateral shifting to the right or left. PMID- 2593598 TI - [Causes and types of eye injuries in miners and employees of coal mines]. AB - One hundred and ninety workers from the coal mines were examined in the years 1977-79 at various work stands and also treated as out-patients and/or hospitalized. The ocular injuries were divided into mechanical trauma and burns. In the analyzed material the percentage of minor trauma amounted 72.5 per cent, severe ocular injuries occurred in 18.5 p.c. of cases; in 4 p.c. ensued a permanent incapacity for work in a coal mine. PMID- 2593600 TI - [Evaluation of the visual system of ophthalmic specialists to assess suitability for the profession]. AB - The author proposes a through ophthalmological examination and selection of the candidates for specialization in ophthalmology. He thinks that the ophthalmic surgeon should have a bilateral full visual acuity with an admittable correction of -1.0 D to +2.0 D, taking into consideration the physiological astigmatism, further--normal color discrimination, efficient adaptation and stereoscopic vision. Only such ophthalmic specialist is able to correctly evaluate the patients eye through the period of his professional activity. PMID- 2593601 TI - Gastroduodenal pathology and Campylobacter pylori. Second meeting of the European Campylobacter pylori Study Group. October 12-14, 1989, Ulm, FRG. Abstracts. PMID- 2593602 TI - [Characteristics of night sleep of monkeys on the ground and during space flight on "Kosmos-1667"]. AB - The data on the sleep structure of two rhesus monkeys, Vernyi and Gordyi, during their 7-day space flight on Cosmos-1667 and a control study staged a month after recovery are discussed. Sleep structure was changed to the greatest extent the night before launch when additional stress factors were involved. During the first night in space Vernyi showed the so-called recoil effect. Later his sleep structure became stabilized: the specific weight of fast sleep diminished and the fast sleep/delta/sleep index in the first two cycles decreased. In the ground based control study, sleep parameters pointed to a deteriorated health status of the animal: his fast sleep patterns changed and delta-sleep often reached its maximum after a fast sleep episode. In this animal adaptation was associated with fast sleep restructuring. In the second primate, Gordyi, the process of adaptation was extended and took three nights. This animal consistently showed low parameters of delta-sleep during both fright and postflight control study; it exhibited no recoil phenomenon after its reduction in the prelaunch night. The structure of sleep indicated that it played a lesser role in the overall process of adaptation. PMID- 2593603 TI - [Study of the structure of receptor organs of the vestibular apparatus of rats after space flight on "Kosmos-1667"]. AB - The receptor organs of the vestibular apparatus of rats flown for 7 days on Cosmos-1667 were examined. Serial sections were examined by light microscopy, some utriculus sections by electron microscopy, and otolith membranes by scanning electron microscopy. The fixation method used revealed a distinct structural heterogeneity of the receptor epithelium. In the striola area of the utriculus and sacculus as well as in the central apical area of cristae there are receptor cells surrounded by enlarged cup-like nerve endings. The nerve endings occupy over 70% of the cup-receptor cell complex. The area incorporating the enlarged nerve endings differs in size from animal to animal and from left to right ear in the same animal. The flown rat that was the first to be killed after recovery showed a very well pronounced asymmetry: in the right ear enlarged cups were seen all over the epithelium while in the left ear they were located in distinct spots. Since such changes were not identified in the remaining flown and control rats, it is concluded that they were produced by space flight effects but remained reversible and disappeared after recovery. This paper describes the causes responsible of the changes and their structural and functional relevances as well as other structural modifications that should be considered during vestibular studies. PMID- 2593604 TI - [Growth and development of unicellular algae in the algae-bacteria-fish biocenosis system during space flight]. AB - The population of Chlorella cells flown as a component of the algobacterial cenosis--fish system on Cosmos-1887 was investigated. During the flight experiment over two generations of Chlorella cells were obtained. No differences in the algal growth rate in flight and on the ground were observed. On the whole, space flight did not affect the growth, development or population characteristics of Chlorella algae incorporated into the closed algobacterial cenosis-fish system. PMID- 2593605 TI - [Study of the growth and development of Chlorella on "Kosmos-1887"]. AB - The growth, development and population characteristics of Chlorella cells flown for 13 days in space were investigated during their postflight cultivation. The growth rate of flown algae did not differ from that of ground-based controls in terms of increases in the cell number and biomass. All basic parameters of the specimens (generation time, number of developing autospores, time ratio of developmental phases) were ontogentically normal. Exposure of the algae to space flight as a component of the algobacterial cenosis--fish autotrophic heterotrophic system produced no significant effect of the population or individual specimens during their postflight cultivation. PMID- 2593606 TI - [Mineral density of human skeletal bones in modeling of decreased gravity load]. AB - Bone density in different skeletal compartments was measured in 9 healthy volunteers exposed for 370 days to head-down tilting (-5 degrees). Measurements were carried out using noninvasive techniques: quantitative computer tomography and dual photon absorptiometry (mono- and dichromatic). After bed rest no distinct mineral losses were seen in lumbar vertebrae, femoral diaphysis, tibial diaphysis, or forearm bones of most subjects. Mineral density of the femoral neck decreased in most subjects. The results are discussed with special emphasis on comparative values of the noninvasive methods, variations in the parameters under study during bed rest, and effectiveness of various countermeasures employed. PMID- 2593607 TI - [370-day anti-orthostatic hypokinesia (the tasks and general structure of the studies)]. AB - This paper presents information about the goals, tasks and protocols of a 370-day antiorthostatic hypokinesia study. It describes the use of various methods of research and different countermeasures. PMID- 2593608 TI - [Tolerance of functional and exercise tests during 1-year antiorthostatic hypokinesia]. AB - During 370 days 9 healthy young volunteers were exposed to antiorthostatic hypokinesia. Group A consisting of 4 subjects performed exercises similar to those regularly made by Mir crewmembers and Group B consisting of 5 subjects did not exercise for 120 days and then performed experimental exercise regimens. It was demonstrated that the health status of men long exposed to head-down tilting can be controlled with the aid of various countermeasures. As a result of the exposure, orthostatic and exercise tolerance diminished. In view of the fact that the changes observed were more pronounced in the Group B subjects, it can be concluded that the countermeasures used were more effective in Group A subjects. PMID- 2593609 TI - [Body fluids during 120-day anti-orthostatic hypokinesia]. AB - Body fluid variations were examined during 120-day antiorthostatic (-5 degrees) hypokinesia in 21 test subjects, 9 of which comprised a control group (Group 1). The remaining 12 subjects formed three groups (four subjects each) who received drugs to normalize mineral and lipid metabolism (Group 2), or performed specially developed exercises (Group 3), or were on the combined treatment (Group 4). Total body water (TBW), intracellular fluid volume (IFV), extracellular fluid volume (EFV), and EFV composition were measured by nuclear physical methods. Measurements were taken prior to exposure, on head-down tilt days 1, 60 and 120, and on recovery day 15. Body composition and K40 content were investigated before and after head-down tilt. The controls showed body dehydration that began on tilt day 1 at the expense of vascular fluid and continued by day 60 at the expense of interstitial fluid and by day 120 at the expense of IFV. Group 2 subjects exhibited variations that were similar to those of controls. Group 3 subjects were in better shape due to the beneficial effect of exercise which diminished as head-down tilt continued. In the recovery period the above changes regressed. PMID- 2593610 TI - [Orthostatic tolerance and the status of central and peripheral hemodynamics during 7-day "dry" immersion in persons with neurocirculatory asthenia of the hypertensive type]. AB - Eleven healthy male volunteers, aged 45-55 years, with neurocirculatory dystonia of the hypertensive type were exposed to 7-day dry immersion. The following parameters were measured: central and peripheral hemodynamics (by the method of rheography), linear blood flow velocity, and orthostatic tolerance before and after immersion. During an acute period of adaptation to immersion the test subjects developed: centralization of blood filling of the head and lungs, decrease of stroke volume and cardiac output, increase of linear blood flow velocity in forearm arteries and its decrease in leg arteries, drastic decline of orthostatic tolerance. PMID- 2593612 TI - [Contractile function of the heart in rats after chronic stress and thyroidin treatment]. AB - We examined heart tolerance of rats, that had been exposed to two-month social stress, to acute overload caused by aortic coarctation and investigated physiological doses of thyroid hormones used to treat stress-induced tolerance changes. Cardiac contractility of rats adapted to chronic stress and exposed to overload was similar to that of controls and the functional maximum reached at the 5th second of aortic coarctation was 33-53% higher than that in the controls. However, tolerance of chronically adapted hearts measured by their ability to maintain increased contractility during 25 s aortic coarctation was 1.4-1.8 times lower. Thyroid hormones in physiological doses normalized tolerance of chronically stressed hearts to overload induced by aortic coarctation. PMID- 2593611 TI - [Changes in the mitochondrial oxidative enzyme activity in the skeletal muscles od rats during the recovery period after hypokinesia of varying duration]. AB - Enzyme activity was measured in 164 white rats exposed to hypokinesia of varying duration. NAD- and NADP-dependent isocitrate dehydrogenases (ICDH) decreased on hypokinesia day 7 and returned to normal on recovery days 4-5. Their enzyme activity was diminished on hypokinesia day 15. NAD- and NADP-dependent ICDH returned to normal on recovery days 11 and 7, respectively. Activity of alpha ketoglutarate dehydrogenase (KGDH) and succinate dehydrogenase (SDH) decreased immediately after hypokinesia and remained lowered till day 18. Activity of pyruvate dehydrogenase (PDH) was decreased on recovery days 1-3 and increased on days 9-17. After 30-day hypokinesia PDH activity was lower than normal on recovery days 2-14. 30-day hypokinesia led to reduction of ICDH, KGDH, and SDH. NADP-dependent ICDH returned to normal on recovery day 12 and other enzymes during the third week of readaptation. These results suggest that during recovery the enzymes that are responsible for energy metabolism restoration are first to return to normal. PMID- 2593613 TI - [A raster method for the analysis of the periodic structure of biorhythms]. PMID- 2593615 TI - [Reaction of skin tissue basophils to exogenous hypoxia in rats: the study of various correlations]. PMID- 2593614 TI - [Effect of increased consumption of plant proteins during hypokinesia on various indicators of calcium metabolism in rats]. PMID- 2593616 TI - [Psychophysiological characteristics of the sensorimotor activity of operators after short-term simulated weightlessness]. AB - Changes in operator's sensorimotor activity and their effect on the control of a dynamic object after short-term exposure to simulated hypogravity were investigated. Hypogravity effects were simulated by a 6-day head-down tilt (-10 degrees) study and a 1-day water immersion study. Changes in the structure of actions seen after study (greater use of controllers in the longitudinal axis, alteration of bioelectric activity of muscles involved in movement arrangement, shift of their spectral power toward higher frequencies) are considered as objective indicators of disrupted automatism of controlling skills. A peculiar psychic compensation of disorders in the coordination structure of movements was a longer time used to control the position and movement of an object in the longitudinal plane. Partial disruption of automatized controlling skills after short-term exposure to simulated hypogravity facilitates a decrease in operator's reliability, when he is to perform sophisticated and precise functions. PMID- 2593617 TI - [Acid resistance of erythrocytes at different rates of induction of constant magnetic field]. PMID- 2593618 TI - [Pathogenesis of the neurologic form of decompression sickness in rabbits]. PMID- 2593619 TI - [Urinary incontinence in older patients. Towards quality nursing]. PMID- 2593621 TI - [Honoring Marjorie Duvillard. Interview by Elfriede Schlaeppi]. PMID- 2593620 TI - [Teachers in nursing schools are asking questions]. PMID- 2593622 TI - [Common interest groups for intensive care staff]. PMID- 2593623 TI - [Measures against burnout]. PMID- 2593624 TI - [Patient care planning--especially for AIDS]. PMID- 2593625 TI - [An anchor for AIDS patients]. PMID- 2593626 TI - [Meeting of the Swiss Society for Health Policies "for reformable health policies". Movement in the nursing professions]. PMID- 2593627 TI - [After the events in the Lainz Hospital in Vienna: intensive investigation of the scene of the crime]. PMID- 2593628 TI - [Health visitor. When undigested experiences and unanswered questions accumulate: continuing education, that moves us forward]. PMID- 2593629 TI - [Nursing practice: between idealism and realism]. PMID- 2593630 TI - [Swiss professional group Oncology]. PMID- 2593631 TI - [Primary health care--an African example poses questions]. PMID- 2593632 TI - Perches for primate squeeze cages. PMID- 2593633 TI - Amyloidosis in pigtailed macaques (Macaca nemestrina): epidemiologic aspects. AB - A retrospective study of amyloidosis in pigtailed macaques (Macaca nemestrina) at the Washington Regional Primate Research Center (WRPRC) was conducted. Between 1971 and 1985, 248 of 1,952 (13%) necropsies revealed amyloidosis in pigtailed macaques. The influence of demographic factors, diseases and experimental interventions on amyloidosis was examined. Univariate analyses, using two controls for each case, indicated that age, sex, birthplace and residence were related to amyloidosis. After adjusting for age, females were not at greater risk. However, monkeys born at the WRPRC were at greater risk and monkeys 0 to 5 years old residing at the breeding colony were at greater risk than monkeys at the research center. After adjustment for age, monkeys were at greater risk of developing amyloidosis if they had a history of episodes of diarrhea, respiratory disease or trauma. As the number of episodes increased, the risk increased. Monkeys with retroperitoneal fibromatosis, a manifestation of simian D retrovirus infection, were also at greater risk. Using logistic regression and controlling for age, sex, birthplace and residence, monkeys with diarrhea remained at an elevated risk for amyloidosis. Compared with a model combining diarrhea, respiratory disease, septicemia, surgery, trauma and retroperitoneal fibromatosis, a model with diarrhea alone accounted for most of the increased risk. PMID- 2593634 TI - Amyloidosis in pigtailed macaques (Macaca nemestrina): pathologic aspects. AB - The pathologic aspects of 248 cases of amyloidosis in pigtailed macaques (Macaca nemestrina) at the Washington Regional Primate Research Center from 1971 through 1985 were studied. Amyloid was present in the spleen, liver and gastrointestinal (GI) tract, either alone or in combination, in nearly 75% of the monkeys. Its occurrence declined with age in the spleen and the GI tract, but increased with age in the liver. Both intestinal inflammation and retroperitoneal fibromatosis were strongly associated with amyloid deposition in the GI tract. Monkeys with histopathologic findings of enteritis or enterocolitis and glomerulonephritis were at increased risk of developing amyloidosis. Forty cases of amyloidosis with a history of chronic diarrhea had type AA amyloid by histochemical tests. PMID- 2593635 TI - Estimation of minimum alveolar concentration (MAC) for halothane, enflurane and isoflurane in spontaneously breathing guinea pigs. AB - MAC for halothane, enflurane and isoflurane was determined in guinea pigs (Cavia porcellus) exposed to constant anesthetic concentrations (2.5 hours each) in a flow-through glass chamber. The following values were obtained (N = 8 for each anesthetic): 1.01 +/- 0.03 vol% for halothane, 2.17 +/- 0.04 vol% for enflurane, and 1.15 +/- 0.05 vol% for isoflurane. In guinea pigs, MAC for halothane and enflurane are similar to those reported for other rodents, while MAC for isoflurane is lower. The data indicate that guinea pigs possibly are more susceptible to isoflurane's anesthetic actions than other rodents. PMID- 2593636 TI - Antigen delivery to gut associated lymphoid tissue of rabbits. AB - A rabbit model was developed so that antigens, microbes or potential mucosal vaccines could be delivered in multiple doses directly to the luminal surface of the gut associated lymphoid tissue (GALT) located in the cecal appendix. A polyethylene catheter was implanted surgically into the tip of the appendix. It exited the body wall and progressed subcutaneously around the thorax to the dorsocervical region where it was attached to a subcutaneous obturator. The catheters were flushed every day with sterile saline. To assess patency of the system, radiographic contrast media was injected and the animals were radiographed. Rabbits were necropsied at 10, 30 and 60 days and tissues evaluated by histological, immunohistochemical and electron microscopic means. The microbial flora was evaluated also. All tissues examined were free of significant abnormalities. The advantage of this delivery system is its ability to provide multiple doses of immunogenic agents directly to a physiologically normal appendix over an extended period. PMID- 2593637 TI - Oral KCl dietary supplement extends survivability of dogs with Heidenhain pouch gastric fistulas. AB - Supplementing the food of Heidenhain pouch gastric fistula dogs with a KC1 product greatly extends the survivability of these dogs. Since there is a continuous discharge of gastric juice from the pouch to the exterior each time a meal is consumed, clinical signs such as dehydration, anorexia, rough hair coat and lethargy usually occur within a few months after gastric pouch surgery and, unless extensive supportive measures are taken, most dogs will die shortly thereafter. The five dogs which did not receive KC1 supplementation died within 6 months after surgery with a mean survival time of 2.4 +/- 0.9 months. Seven dogs that received a daily oral supplement of 1.5 g KC1 (20 mEq) in their food have, on average, survived more than ten times longer than dogs which received no KC1 supplementation, with a mean survival time of 25.1 +/- 4.4 months. All KC1 supplemented dogs survived for more than 15 months with three dogs currently surviving for 36-40 months. When two dogs experienced decreased serum potassium, sodium and/or chloride levels and showed clinical signs of electrolyte imbalance despite receiving daily oral KC1 supplementation, intervention with intravenous (i.v.) lactated Ringer's solution and increased amounts of oral KC1 supplement reversed these symptoms within 1-2 weeks. Dogs that received only i.v. Ringer's therapy died with 1 week of the onset of clinical signs. Daily oral KC1 supplementation, careful observation of behavior and eating patterns, and routine physical examinations and serum electrolyte measurements can greatly extend the life expectancy of dogs with Heidenhain pouch gastric fistulas. PMID- 2593638 TI - The cardiorespiratory effects of diazepam-ketamine and xylazine-ketamine anesthetic combinations in sheep. AB - The cardiorespiratory dynamics and anesthetic effects of intravenously administered diazepam-ketamine (0.375 mg kg-1/7.5 mg kg-1) and xylazine-ketamine (0.1 mg kg-1/7.5 mg kg-1) were investigated in six domestic sheep (Ovis aries). The depth of analgesia and sedation was evaluated and the effects of the anesthetic drug combinations on hemodynamics and pulmonary mechanics were monitored before, and up to 90 minutes after, drug administration. Diazepam ketamine and xylazine-ketamine induced effective anesthesia for periods lasting 15 minutes and 25 minutes, respectively. Both drug combinations caused transient respiratory acidosis. However, no profound effects on respiration or pulmonary function were observed. Neither anesthetic regimen caused significant effects on heart rate or pulmonary hemodynamics, but they caused significant decreases in cardiac output. Xylazine-ketamine resulted in a significant decrease in mean systemic arterial blood pressure (Psa) with a concurrent decrease in systemic vascular resistance (SVR). Diazepam-ketamine caused a significant increase in SVR without affecting Psa. Xylazine-ketamine may be contraindicated in animals with compromised heart function because of its hypotensive effects. Otherwise, both drug combinations, in the doses used, can provide short-term anesthesia suitable for minor surgical procedures and painful experimental maneuvers. PMID- 2593639 TI - Blood volume determinations in sheep before and after splenectomy. AB - Using 51Cr labelled RBCs, total blood volume, red cell volume and plasma volume were measured in fifteen adult, female, domestic sheep both before and after splenectomy. Eight of the fifteen animals studied were anemic. Statistical analyses revealed no significant differences in blood volume parameters whether animals were grouped together or separated into normal and anemic groups. We observed: (a) splenectomy produced modest reductions in blood volume parameters in 12 of 15 animals, (b) preoperative variability in blood volume parameters caused by release of sequestered RBCs from the spleen was eliminated after splenectomy, and (c) equilibration of 51Cr required at least 30 minutes in intact animals, but only 10 minutes in splenectomized animals. After volume parameters were normalized to body weight, they were found to agree closely with values reported previously. This study demonstrates the dynamic function of the sheep spleen in the regulation of blood volume. PMID- 2593640 TI - Effect of T-2 toxin on feed intake, digestion and pathology of rabbits. AB - Feed containing sublethal T-2 toxin concentrations (12.5 and 25 ppm) was fed to adult rabbits. The animals ate 60-70% less toxin-containing food. The dry matter content of their feces decreased significantly (on an average by 10%). The nutrient digestibility of the feed containing 12.5 ppm T-2 toxin, was increased by 2-6% and that of the 25 ppm T-2 toxin level decreased by 4-11% as compared to the control values. The rabbits showed emaciation, subacute catarrhal gastritis, necrosis of the lymphoid cells of the intestinal mucosa, depletion and necrosis in the lymphoid follicles of the ampulla ilei, spleen and lymph nodes. Necrosis of the cells of mononuclear phagocyte system and myeloid hemacytogenesis was characteristic. The toxin concentration of feces, cecotroph and urine was proportional to intake. PMID- 2593641 TI - Diagnostic exercise: vascular disease in a New Zealand white rabbit. PMID- 2593642 TI - A rapid non-surgical technique to obtain serial samples from the gastrointestinal tract using a steerable catheter and fluoroscopy in the rhesus monkey. PMID- 2593643 TI - Megaloblastic anemia in a handreared chimpanzee. PMID- 2593644 TI - Liquid diet preparation for study of chronic alcohol ingestion in the rat. PMID- 2593646 TI - Blood collection and intravenous injection in the guinea pig via the medial saphenous vein. PMID- 2593645 TI - The use of subcutaneous ports in the woodchuck (Marmota monax). PMID- 2593647 TI - Husbandry and hematology of captive spiny mice (Acomys cahirinus). PMID- 2593648 TI - Vacuum-assisted cardiac puncture in chickens. PMID- 2593649 TI - Energy consumption during passive isokinetic exercises. PMID- 2593650 TI - Effect of dietary manipulation on a high intensity performance test. AB - The effects of dietary manipulation (low- or high-carbohydrate) on performance of a short-duration exercise were studied with endurance- and intermittent-trained athletes. Eight subjects performed a depletion drill of 10 one minute workbouts at 7 W/kg and 85 rpm on a cycle ergometer. The subjects followed a dietary regimen of three days on a low-carbohydrate diet followed by three days on a high carbohydrate diet. Muscle biopsy samples were taken immediately prior to and immediately after the testing sessions. Dietary manipulation did not affect resting muscle glycogen levels. However, subjects accustomed to continuous training regimens used less glycogen, produced less muscle lactate and exercised longer than subjects accustomed to intermittent training programs. These biochemical changes appeared to be related to the fibre type distribution and the training background of the athletes. PMID- 2593651 TI - M-mode echocardiography study of twenty-two top class racing cyclists. AB - In this study M-mode echocardiograms were performed on 22 top class racing cyclists in order to assess the incidence of structural heart alterations. A normal control group was composed of 20 sedentary men of similar age and surface body area. Statistical analysis was performed using the unpaired Student t-test. A normal LV mass was found in all athletes and normal left Ventricle diastolic diametre (LVDD) in 13 cyclists. Global and regional LV systolic functions were normal in all cyclists. Mitral valve analysis showed normal LV compliance in all athletes. Thus, the cyclists admitted to our study did not present LV hypertrophy and most of them had normal LVDD. Systolic and diastolic functions were normal in all of them. PMID- 2593652 TI - Validity of anthropometric equations for determination of changes in body composition in adult males during training. AB - Twenty-six males (26.5 +/- 6.0 yr; X +/- SD) were studied before and after a fourteen week endurance training program to determine the validity of anthropometric equations for estimating changes in body composition (BC). Anthropometric measures included skinfolds (SF), circumferences, and diameters. Body density (BD) was determined by underwater weighing corrected for residual lung volume. Training resulted in an increase in BD (1.061 +/- 0.002 to 1.067 +/- 0.002 g/ml; X +/- SEM) and decreases in body weight (73.0 +/- 2.1 to 71.4 +/- 2.0 kg), relative fat (16.6 +/- 0.9 to 14.1 +/- 0.8%), fat weight (12.4 +/- 1.0 to 10.2 +/- 0.8 kg), and seventeen of the anthropometric measures (p less than 0.05). Cross-validation of twenty-four equations revealed validity coefficients (r2) and total error in relative fat (RFE) of r2 = 0.40-0.77 and RFE = 2.60 10.15% before training and r2 = 0.14-0.61 and RFE = 2.62-9.45% after training. Linear and base 10 logarithmic (log10) equations using primarily SF measures tended to have higher r2 and lower RFE than equations based on quadratic and natural logarithmic (loge) models and other anthropometric measures. Paired t tests revealed that of these equations with higher r2 and lower RFE, only the linear equation by Forsyth & Sinning (BD = 1.10647--0.00162(scapSF)- 0.00144(abdSF)--0.00077(triSF++ +) + 0.00071(midaxSF] was a stable predictor of BD during training. These results suggest that many existing equations may not be accurate predictors of changes in BC during training. PMID- 2593653 TI - Anthropometric measurements of adolescent and professional classical ballet dancers. AB - This study examined anthropometric measures of 83 female adolescent students attending the Boston Ballet summer program and 15 professional dancers from the Boston Ballet Company. Thirty-one were in the least advanced level (group A), 38 were in the moderately advanced level (group B) and 14 were in the most advanced level (group C). The adolescent dancers devoted between 17 and 23 hours per week in dance training, while professional dancers spent 39.2 hours per week in class and rehearsals. Compared to normative data, the dancers tended to be tall and slim. The skinfold, diameter, and circumference measurements were found to be very similar among groups A, B and C, and between group C and the company members. The somatograms demonstrated that the ballet dancers had relatively smaller upper arms and larger calves and ankles compared with the reference female. The data from this study suggest that the body type characteristics associated with professional classical ballet dancers are already apparent in the pre-professional adolescent dancers. PMID- 2593654 TI - Menstrual irregularities in athletic women may be predictable based on pre training menses. AB - With the use of a personally conducted survey the age at menarche, incidence of menstrual irregularity, whether training occurred before or after menarche, certain personality traits (anxiety, curiosity, anger), and the type of athletic activity performed, were assessed in 161 highly competitive women athletes of various types (e.g. professional dancers, basketball players, fencers, gymnasts, field hockey players, swimmers) and 65 age-matched nonathletic women. No significant difference was found between the mean age at menarche of competitive athletes 13.2 +/- 1.4 (SD) yrs and nonathletes 12.6 +/- 1.1 yrs or between athletes who trained before menarche 13.7 +/- 1.5 (SD) yrs compared to athletes who trained after menarche 12.7 +/- 1.3 yrs. However, there were significant differences in reference to the mean age at menarche for athletes and nonathletes when compared to current menstrual frequency (p less than 0.05) and for groups of athletes currently regular 12.9 +/- 1.2 (SD) yrs when compared to those currently irregular 13.4 +/- 1.6 yrs (PR greater than F = 0.0419), regardless of athletic status. Trait personality characteristics (anxiety, curiosity, anger) based on the Spielberger State-Trait Personality Inventory (STPI), showed no significance among the various athletes, or athletes compared to non-athletes, however, athletes having the highest mean anxiety scores 19.5 +/- 4.2 (SD) and lowest mean anger scores 17.0 +/- 3.6 (SD) had irregular menses. Predictability for the development of irregular menses was done by regression and stepwise discrimination with maximum improvement technique statistics using pre-training frequency of menses and post-training frequency of menses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593655 TI - Potassium content of the fat free body in children. AB - Previous estimates of body composition in children by measurement of total body potassium (TBK) have employed adult derived values for the ratio of K/fat free body mass (FFBM) to calculate the FFBM. To evaluate the appropriateness of this practice, body composition was determined in 30 children (14 boys, 16 girls) between the ages of 9 and 14 years by hydrostatic weighing, bioelectric impedance, and whole body counting of 40K. Estimates of body fat percentage by TBK measurements were significantly greater (p less than 0.05) than by either the hydrostatic or bioelectric impedance techniques. When current estimates for the FFBM density in children were employed to derive the K/FFBM, the value for boys was 58.9 mEq and for girls, 54.2 mEq. These data indicate that the FFBM will be underestimated in pediatric populations when adult derived values for K/FFBM are used. PMID- 2593656 TI - Effect of yogic training on serum LDH levels. AB - LDH is a glycolytic enzyme utilised during exercise to provide energy to contracting muscles. Chronic submaximal exercise for a longer duration shows about two-fold increase in LDH levels. Yogic practises might be bringing similar effects. The present work was designed to study effect of yogic training on LDH levels. Fourteen female and six male students of average age or 18 years were subjected to yogic training for six weeks. Serum LDH levels were found before and after the training course by spectrophotometric method of Henry et al. The serum LDH levels were within normal limits and showed significant increase both in females and males after yogic training. It indicates that Yoga has similar effect on LDH levels like endurance training. PMID- 2593657 TI - Effect of a season of competition and training on hematological status of women field hockey and soccer players. AB - "Sports anemia" has been observed in the early periods of physical training and may be unfavorable for sport performance and resistance to fatigue. The purpose of this study was to see what effect competition and training had on the hematological status of women field hockey and soccer players. Thirty collegiate athletes participated in this 14 week study. Blood samples were drawn prior to the start, mid-point, and end of the sport season and analyzed using a J.T. Baker 700 A analyzer. Results indicated that mean values for hemoglobin, hematocrit, mean corpuscular volume, and red blood cell count increased over time for both experimental and control groups. Values for all hematological parameters were within the normal ranges for females. Since all blood parameters commonly used to assess iron hematology were within normal ranges, we can conclude that "sports anemia" was not present. PMID- 2593658 TI - The effect of low impact dance training on aerobic capacity, submaximal heart rates and body composition of college-aged females. AB - The purpose of this study was to examine the effects of a 12 week program of low impact aerobic dance conditioning on VO2max, submaximal heart rates and body composition of college-aged women. Sixteen women exercised three times per week for approximately 45 minutes per session at 75-85% of their heart rate reserve. VO2max was measured by indirect calorimetry using a treadmill protocol. Submaximal heart rates were measured by electrocardiography, and body fat was assessed by hydrostatic weight. All testing was conducted within one week pre- and posttraining. Training sessions consisted of a 5-10 minute warm up, 30-35 minute low impact aerobic dance segment and a 5 minute cool down. Posttest results revealed a small (7%), but significant increase in VO2max (pre: 38.3 ml/kg/min; post: 41.3 ml/kg/min, X +/- SD, p less than 0.05). Submaximal heart rates at minutes 2-3, 3-4 and 4-5 of the graded exercise test decreased significantly. Body fat decreased from 25 +/- 6.8% to 21 +/- 6.3% (p less than 0.01) with no posttraining change in body weight. It was concluded that low impact aerobic dance is as effective as other endurance training regimens in improving cardiovascular fitness and decreasing body fat. PMID- 2593659 TI - Functional assessment of high level ice-dancing. AB - In these studies the anthropometric characteristics and some functional characteristics of ice-dancers are analysed. It has been shown that the maximum oxygen uptake is similar to that of classical ballet dancers. Tests effected on the ice revealed a high production of lactate, the involvement of the anaerobic metabolism, and high heart rates. It is concluded that the high production of lactate during the free dance on ice is due to the isometric muscular contraction, necessary to maintain certain positions. PMID- 2593660 TI - Hamstring/quadriceps strength ratios in knees with medial collateral ligament insufficiency. Isokinetic and isometric results and their relation to patients' long-term recovery. AB - The purpose of this study was to investigate the peak torque and total work hamstring/quadriceps strength ratios (HQ-ratios) of 25 knees with medial collateral ligament (MCL) insufficiency and to find out the possible relation between different HQ-ratios and the long-term outcome of the patients. The isokinetic (speed 60 and 180 degrees/sec) and isometric muscle strengths were measured by a Cybex II dynamometer. Three standardized knee scoring scales were used to determine the subjective, clinical, and radiological outcome of the knees with MCL insufficiency. All tests showed great interpersonal variation in HQ ratios even in the healthy knees (range from 23% to 183%). The average HQ-ratios between the uninjured and injured legs did not differ significantly from each other (range from 40% to 82%). The mean peak torques and total work of hamstrings as well as of quadriceps were slightly, but not significantly lower in the injured leg than on the uninjured side. The follow-up scores did not differ significantly between patient groups with low (less than or equal to 50%), optimal (50-80%), or high (greater than or equal to 80%) absolute HQ-ratios of the MCL insufficient knee. However, in every test the scores were significantly better for patients with an HQ-ratio difference of less than or equal to 15% between the injured and the uninjured side than for those with a clear difference (greater than 15%). The findings suggest that the HQ-ratio is a patient-specific parameter and that any general recommendation on its optimal value is difficult to give.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593661 TI - Motor cycle injuries in speed sport for youngsters. AB - In speedsport motorcycling for youngsters (6-16 years) is gaining an increasing popularity. We had the impression that there was an increase in the number of injured young motorcyclists. Therefore we studied the kind, cause and severity of the injuries sustained to 32 young motorcyclists treated in the Department of Traumatology of the University Hospital Groningen. This group consisted of 31 boys and one girl, aged 7 to 16, with an average age of 13.3. The severity of the injuries varied from sprain and strain of joints to compound bone fractures and twice a rupture of the liver. 29% of all patients were treated as in patients. Our conclusion from this study is that there was a considerable increase in number of injured young motorcyclists as well as in severity of the injuries. In this study we discuss some suggestions for accident prevention. PMID- 2593662 TI - Predicting success in football. AB - Clinical interviews were held with the rated most successful starting players for each position on a college football team. Mental strategies associated with major sensory systems were determined for each player through observation of eye movement patterns and players' usage of sensory based words. Mental strategies for motivation, creativity, belief, learning, decision making, and memory were assessed through these observations. Both offensive and defensive winners have a high visual lead. The auditory sensory modality is LEAST utilized. Creativity and decision making are dominated by the visual sense. Mental strategies for motivation, belief, and memory are balanced between visual and kinesthetic sensory modalities. In future studies clinical observations suggestive of sensory based mental strategies can be combined with empirically validated personality test data to increase predictive power in the selection and placement process with college and professional football players. This should reduce costs of selection and placement errors caused by hitherto undetected psychological factors. PMID- 2593663 TI - Ocular melanoma in Alberta: a 38 year review pointing to the importance of tumor size and tumor histology as predictors of survival. AB - A large number of cases of ocular melanoma have been entered in The Provincial Cancer Registry of Alberta over the past 40 years. This study was undertaken in order to describe further the natural history of this disease and derive management recommendations for use at the provincial level. A retrospective chart review was carried out on all cases of ocular melanoma registered through The Alberta Provincial Cancer Registry between 1949 and 1987. Two hundred fifty-one cases were identified: 143 were males and 108 were females. The mean age of the patients at diagnosis was 60. The majority of the melanomas arose from the choroid of the eye (82%) with the remainder arising from the iris, conjunctiva and ciliary body, respectively. According to the Callender classification for ocular melanomas, the majority of the melanomas were of the spindle cell type (53%), the others being either mixed cell (23%), epithelioid (8%), or fascicular (1%). Survival rates differed depending on the cell type. Spindle cell tumors demonstrated a mean survival time of 5.2 years; epithelioid tumors 4.8 years and the mixed cell tumors appeared to be the most aggressive with a mean survival time of 2.7 years after diagnosis. The majority of deaths from ocular melanoma occurred within 5 years of diagnosis, although 14% of patients in this review presented with metastases more than 10 years after diagnosis. Some of the cases of ocular melanoma could be classified pathologically as small, medium, or large. Patients with large ocular melanomas had a 5 year survival rate of 33% compared to 70% and 66% for patients with small and medium sized tumors. Of note, 43% of patients with large ocular melanomas who were dead from their disease within 5 years of diagnosis were also found to have mixed cell tumors. These findings call for a longer follow-up period for ocular melanomas and point to the importance of cell type and tumor size as predictors of survival and as guides in planning prophylactic therapeutic interventions. PMID- 2593664 TI - Histopathologic evaluation of survival time in patients with colorectal carcinoma. AB - A histopathologic study was done on tissues from 117 patients with colorectal carcinoma, and we compared data on 57 patients who died of a recurrence within 2 years (group I) with 60 others who survived for over 10 years (group II). All patients were surgically treated and followed for over 10 years. Particular attention was directed to the very advancing margin of the tumor, and we examined invading modes of sprouting tumor cells, reactive fibrosis, and inflammatory infiltration around the tumor, in addition to the other clinicopathologic features. In group II, extensive sprouting of individual tumor cells occurred less often, and intense reactive fibrosis and marked inflammatory infiltration around the tumor were more frequent than in group I in which conspicuous lymphatic and vascular permeations were often present. We propose that the invading mode of sprouting tumor cells and the presence or absence of reactive fibrosis and inflammatory infiltration at the advancing margin of the colorectal tumor are of prognostic value. PMID- 2593665 TI - Bone and liver imaging in regionally advanced melanoma. AB - The clinical records of 94 patients with regionally advanced melanoma (nodal disease or regional satellites) were reviewed to determine the value of preoperative bone and liver imaging. Of 68 bone scans obtained, none were suggestive of metastases. of 97 liver imaging studies (computed tomography, scintiscan, or sonography) in 88 patients, only two were found to have demonstrable metastases. Liver enzyme elevation was present in both of these patients. Bone and liver imaging in the absence of signs or symptoms of dissemination by history, physical examination, chest x-ray, and enzyme determination for regionally advanced melanoma appears to be of little value unless the patient is involved in a protocol study. PMID- 2593666 TI - Hypercalcemia related to the poor prognosis of patients with squamous cell carcinoma of the esophagus. AB - A review of 208 cases of surgically treated squamous cell carcinoma of the esophagus revealed 16 (7.7%) with hypercalcemia. There was no evidence of bone metastases in 13 (6.3%) of the patients with hypercalcemia. Pathogenesis of this hypercalcemia without bone metastases was suggested to be multifactorial. Anastomotic leakage and malnutrition because of fasting were the most possible causes of mild hypercalcemia, and moderate to severe hypercalcemia was thought to be due to subclinical and clinical recurrence of the tumor, probably with PTH like hormonal activity. Overall survival rates in the groups with and without hypercalcemia were 18.2 and 61.7% at the 12th postoperative month and 9.1 and 37.8% at the 24th month, respectively. Thus hypercalcemia is a significant prognostic factor linked to an unfavorable clinical course even in patients with no evidence of bone metastases. PMID- 2593667 TI - Diagnostic value of cervical lymph node biopsy: a pathological study of 596 cases. AB - During a 10-year period (1976-1985), a total of 596 cervical lymph node biopsies for diagnostic purposes were performed at our institution. Thirty-five percent of these nodes were involved with malignant lymphoma, and 20.5% showed metastatic deposits. Nondiagnostic reactive hyperplastic changes were noted in 23% of the cases. Several other inflammatory and neoplastic conditions were encountered. Comparison of our data with several series from different countries with review of relevant literature are presented. PMID- 2593668 TI - Observations on Indian node-negative breast cancer patients: a multivariate analysis. AB - The modern treatment of breast cancer has evolved over the past 100 years based on clinical observations. Therapeutic principles, from the choice of surgical procedure to the management of disseminated disease, have also changed. The axillary tumour burden, that is, the number of histologically positive nodes (N+) plays an important role as a prognostic factor. However, in histologically Negative nodes (N-), it is necessary to discriminate individuals at high risk despite negative nodes. This presentation analyses retrospectively the prognostic factors for long-term failures in N- patients. These prognostic factors need to be studied in detail, and controlled clinical trials should be carried out to detect high risk N- patients and consider them for adjuvant chemotherapy. PMID- 2593669 TI - Declining trend in cervical cancer incidence in Bombay, India (1964-1985). AB - Population-based incidence rates for cervical cancer in Bombay showed a decline over the past two decades. The observed rates fitted to a log linear regression model showed a good fit. In an attempt to explain the observed decline, cohort specific age incidence curves were drawn, cumulative incidence rates over common age ranges estimated, and the log linear model fitted separately for each of the religious groups that showed diverse age-adjusted rates for cervical cancer. It was found that the decline could be explained as a cohort effect, indicating that it was due to an upward shift in age at marriage in the younger cohorts. Furthermore, a significant decline was observed in Hindus in whom the mean age at marriage has increased from 12 years in 1921-1931 to about 17 years in the 1960s, but not in the Christians who even in 1911 had a mean age at marriage of 17 years. It appears that, in India, cervical cancer rates will continue to decline until 1995 after which it will stabilise unless there is a change in other risk factors. PMID- 2593670 TI - An intercalative and minor groove binding model for the DNA cleavage reagent, copper(I) (1,10-phenanthroline)2. AB - On account of the stereochemical structure and interaction characteristics of the DNA cleavage reagent copper(I) (1,10-phenanthroline)2, both intercalative and minor groove binding modes to B-DNA could be expected to occur. In the proposed model, the suitable dihedral angle between phenanthrolines allows that one of the two planar ligands partially intercalates between base pairs, and meanwhile the other ligand locates along the minor groove. PMID- 2593672 TI - Oscillations in the evolution of reciprocity. AB - A game-theoretical analysis of the Iterated Prisoner's Dilemma shows that the evolution of ensembles of stochastic strategies displays a dynamics of high complexity and unpredictability. PMID- 2593671 TI - Kinetic model of the effects of electrogenic enzymes on the membrane potential. AB - Electrogenic enzymes contribute to the electrical field existing across biological membranes by using a source of free energy to generate an ionic current. The model introduced here permits one to evaluate this contribution. Since the model incorporates the electrogenic enzyme in the form of a sequential kinetic diagram, it permits one to study the kinetic effects of the concentration of the enzyme, the substrates and the different ligands on the membrane potential. Ionic electrodiffusion is expressed in terms of a chemical reaction; ionic permeabilities are thus treated as voltage-dependent rate constants. We use the condition of global electroneutrality to obtain an expression for the electrical potential difference across the membrane; such expression constitutes an extension of the Goldman-Hodgkin-Katz equation. The enzyme-related terms appear in the equation as functions of the rate constants and the diverse concentrations. The model is used to analyze the case of a cell membrane traversed by Na+ and K+ by simple diffusion, and by electrogenic transport mediated by a Na+-K+ ATPase. The enzyme reaction is represented by the six-step scheme proposed by Chapman et al. (1983, J. membr. Biol. 74, 139-153). The main results of the numerical calculations are that, within a certain interval, the membrane potential difference depends linearly on the enzyme density and hyperbolically on the ATP concentration. A similar behavior has been experimentally observed for the electrogenic proton pump of Neurospora crassa. Thus, the model here can be useful in the explanation and prediction of effects of electrogenic enzymes on the membrane potential. PMID- 2593673 TI - Modeling survival of experimentally virus-infected laboratory animals. AB - Although survival analysis is a well-established mathematical discipline, there seem to be almost no attempts in survival modeling for experimentally virus infected laboratory animals. We have taken up a stochastic approach originally developed by Shortley in the sixties and have applied it to three different types of experimental data: to virus titer determination, to the dose dependence of the mean survival time and to single survival curves. Experience concerning parameter estimation is reported and new ways of working with the model parameters are proposed. A standard mean survival time is defined and suggested as a new quantitative measure of virulence. Moreover, for the comparison of two experiments for which the amount of virions inoculated is kept fixed, but for which other parameters may vary, a new scheme of systematizing survival data from experimentally virus-infected laboratory animals is proposed. It is very likely that the model can be also applied to cancer survival data or any other infectious pathogen. PMID- 2593674 TI - A general model for the evolution of nuclear pre-mRNA introns. AB - We present an overview of the evolution of eukaryotic split gene structure and pre-mRNA splicing mechanisms. We have drawn together several seemingly conflicting ideas and we show that they can all be incorporated in a single unified theory of intron evolution. The resulting model is consistent with the notion that introns, as a class, are very ancient, having originated in the "RNA world"; it also supports the concept that introns may have played a crucial role in the construction of many eukaryotic genes and it accommodates the idea that introns are related to mobile insertion elements. Our conclusion is that introns could have a profound effect on the course of eukaryotic gene evolution, but that the origin and maintenance of intron sequences depends, largely, on natural selection acting on the intron sequences themselves. PMID- 2593675 TI - Magnetic potential and field gradients of a model cell. AB - The magnetic potential within and outside a nucleated cell placed in a uniform magnetic field is described for a model consisting of two concentric diamagnetic spheres. The analytical description of the magnetic potential in and around a system consisting of a finite number of concentric diamagnetic spheres in a uniform magnetic field was derived. The solution was employed to calculate the field gradients outside and inside a model chicken red blood cell. The form and magnitude of the gradients provide a theoretical basis on which to discuss experimental results relating to the attenuation of signals obtained using proton nuclear magnetic resonance spectroscopy with chicken erythrocyte suspensions. The form of the magnetic field, field difference and field gradients in the external medium of a cell suspension was simulated for a distribution of spheres in a uniform magnetic field, such as might occur in an idealised dilute cell suspension. PMID- 2593677 TI - A mathematical model of the gate control theory of pain. AB - The first test which any theory of pain must pass is that it must be able to explain the phenomena observed in acute pain in humans. This criterion is used to test the major theory of pain at present, the gate control theory of Melzack & Wall (1965, 1982). The theory is explicit enough to be cast in mathematical terms, and the mathematical model is shown to explain the observations considered. It also points up a common misconception on the consequences of the theory, and thus demolishes an argument which has been used against it. A hypothesis of the origin of rhythmic pain is then made, and consequent testable predictions given. This is the first time that the gate control theory has been used to explain any quality of pain. It has important consequences for the treatment of such pain. Finally, the applicability of the gate control theory as an explanation for chronic pain is discussed. PMID- 2593676 TI - Conformation of surface bound polyelectrolytes: I. Implications for cell electrophoresis. AB - We present a self-consistent calculation for a layer of short-chain polyelectrolytes grafted to a planar interface. Individual self-avoiding chain configurations are generated on a tetrahedral lattice. By evaluating the complete ensemble of configurations in the presence of a self-consistent field we determine averages for the equilibrium layer height, segment and charge density profiles. These describe the response of the layer to changes in the surrounding medium, in particular to electrolyte concentration. This self-consistent model of a biological cell, which is known to have an extended layer of charge exterior to the membrane bilayer surface, is applied to the problem of cell electrophoretic mobility. We compare the electrophoretic mobility deduced from the application of this model with that for a constant profile of charge and segments and with the case of a constant segment profile with a plane of charge, usually assumed in the literature. We find that, within the region of concentrations studied here and with the chain lengths used, there is general agreement between the different descriptions. PMID- 2593678 TI - Geometrical aspects of surface morphogenesis. AB - This paper is concerned with the morphogenesis of structures which form thin deformable sheets. A general formalism is presented for the deformation of a sheet in the presence of an isotropic local body stress. This formalism leads to a set of equations, based on the theory of shells, in which corrections are made in the geometry due to large deformations. Under certain conditions the equations may be solved to give the surface metric tensor as a function of the local tension. A numerical example based on a simple "threshold" model is also presented. PMID- 2593679 TI - Gap costs for multiple sequence alignment. AB - Standard methods for aligning pairs of biological sequences charge for the most common mutations, which are substitutions, deletions and insertions. Because a single mutation may insert or delete several nucleotides, gap costs that are not directly proportional to gap length are usually the most effective. How to extend such gap costs to alignments of three or more sequences is not immediately obvious, and a variety of approaches have been taken. This paper argues that, since gap and substitution costs together specify optimal alignments, they should be defined using a common rationale. Specifically, a new definition of gap costs for multiple alignments is proposed and compared with previous ones. Since the new definition links a multiple alignment's cost to that of its pairwise projections, it allows knowledge gained about two-sequence alignments to bear on the multiple alignment problem. Also, such linkage is a key element of recent algorithms that have rendered practical the simultaneous alignment of as many as six sequences. PMID- 2593680 TI - Electrical instability in cardiac muscle: phase singularities and rotors. AB - A dynamical system is "excitable" at some stage in its behavior (e.g. at a rest state or while it is nearly at rest prior to a spontaneous event) if a small, but not too small, stimulus of the right kind elicits an immediate big reaction that eventually leads back to the original state. During this return to excitability a typical system is not excitable. An excitable system need not have an attracting rest state; a spontaneous oscillator can be excitable, too, as is common in biological and in chemical excitable kinetics. In a medium characterized by such excitable dynamics at every point, the excitation can propagate as a travelling pulse. Undamaged cardiac muscle shares with other excitable media certain features of such pulse propagation in two and three dimensions. Among the new electrophysiological phenomena thus anticipated are paired mirror-image vortices ("rotors") organized around phase singularities. These should arise in the myocardium near the intersection of a moving critical contour of phase in the normal cycle of excitation and recovery with a momentary critical contour of local stimulus strength. Such intersections, and the corresponding aftermath of paired rotors, should only occur following certain combinations of stimulus size and stimulus timing. Plotting those combinations on a "vulnerability diagram", one delineates a domain for creation of rotors (corresponding to tachycardia) surrounded on all sides by a halo of combinations at which just a few repetitive responses follow stimulation. The experiments called for to check these implications have now been carried out in the special case of electrically induced tachycardia in healthy canine ventricle. They support the two-dimensional theory, so a new experiment is suggested to demonstrate wholly intramural three dimensional vortex filaments. PMID- 2593681 TI - On the evolution of sex in RNA viruses. PMID- 2593682 TI - The study of DNA sequences by their sequences of twist angles. AB - To study the properties of DNA sequences we have transformed the sequences of bases into the sequences of twist angles along the chain of DNA double helix by using the Dickerson sum function. The Fourier transform and the auto-correlation function of the twist angles sequences have been used to study the periodicity and randomness of the original DNA sequences. Basing on the correlation coefficient, a "distance" between two DNA fragments has been defined and used to compare some realistic DNA sequences. It is hoped that the techniques developed here could be used to analyze more realistic DNA sequences. PMID- 2593683 TI - Understanding respirometry chambers: what goes in must come out. AB - An examination of the compartmental dilution washout in metabolic chambers was conducted and new equations for the calculation of "instantaneous" VO2 were derived. Using appropriate compartmental models, an evaluation was carried out on systems used in previous estimates of this parameter. Effects of chamber mixing and sampling times on calculated VO2 values were also examined. Alternatives to resolving "instantaneous" VO2 are presented with emphasis on system design rather than on mathematical manipulation. PMID- 2593684 TI - A model of bursal colonization. AB - In the chicken, and perhaps in all birds, the development of the cells which form antibodies, the B-cells, differs substantially from that in mammals. In birds, committed B-cells colonize a specialized organ, the bursa of Fabricius, which consists of some 10(4) follicles. Diversification, i.e., the development of the antibody repertoire, takes place in bursal follicles by a process termed "gene conversion." The avian bursa is easily accessible experimentally, and in the chicken, it has been the subject of extensive research. As an aid to experimentation in this field, we present here a formal mathematical model of bursal development. Formulae are derived which allow one to estimate the number and sizes of B-cell clones in bursal follicles, and hence the size of the overall antibody repertoire. Particular attention is paid to the problem of estimating experimental errors. PMID- 2593685 TI - Idiotypic networks incorporating T-B cell co-operation. The conditions for percolation. AB - Previous work was concerned with symmetric immune networks of idiotypic interactions amongst B cell clones. The behaviour of these networks was contrary to expectations. This was caused by an extensive percolation of idiotypic signals. Idiotypic activation was thus expected to affect almost all (greater than 10(7] B cell clones. We here analyse whether the incorporation of helper T cells (Th) into these B cell models could cause a reduction in the percolation. Empirical work on idiotypic interactions between Th and B cells however, would suggest that two different idiotypic Th models should be developed: (1) a Th which recognises native B cell idiotypes, i.e. a non-MHC-restricted "ThId" model, and (2) a "classical" MHC-restricted helper T cell model. In the ThId model, the Th-B cell interaction is symmetric. A 2-D model of a Th and a B cell clone that interact idiotypically with each other accounts for various equilibria (i.e. one virgin and two immune states). Introduction of antigen does indeed lead to a state switch from the virgin to the immune state; such a system is thus able to "remember" its exposure to antigen. Idiotypic signals do however, percolate in ThId models via these "B-Th-B-Th" pathways: proliferating Th and B cell clones that interact idiotypically, will always activate each other reciprocally. In the MHC-restricted Th model, Th-B interactions are asymmetric. Because the B cell idiotypes are processed and subsequently presented by MHC molecules, the Th receptor and the native B cell receptor are not expected to be complementary. Thus the Th and the B cells are unable to activate each other reciprocally, and a 2-D Th-B cell model cannot account for idiotypic memory. In contrast to the ThId model, idiotypic activation cannot percolate via "B-Th-B-Th" interactions. Due to the assymmetry idiotypic activation stops at the first Th level. A Th clone cannot activate a subsequent B cell clone: if the B cells recognise the Th cells, they see idiotype but get no help; if the Th cells see the B cells, the B cells are helped but see no idiotype. The percolation along "B-B-B" pathways in these two models is next analysed. Two B cells clones, each helped by one Th clone, are connected by a symmetric idiotypic interaction. It turns out that in both models the second (i.e. anti-idiotypic) B cells (B2) never proliferate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2593687 TI - The inheritance of acquired epigenetic variations. AB - There is evidence that the functional history of a gene in one generation can influence its expression in the next. In somatic cells, changes in gene activity are frequently associated with changes in the pattern of methylation of the cytosines in DNA; these methylation patterns are stably inherited. Recent work suggests that information about patterns of methylation and other epigenetic states can also be transmitted from parents to offspring. This evidence is the basis of a model for the inheritance of acquired epigenetic variations. According to the model, an environmental stimulus can induce heritable chromatin modifications which are very specific and predictable, and might result in an adaptive response to the stimulus. This type of response probably has most significance for adaptive evolution in organisms such as fungi and plants, which lack distinct segregation of the soma and germ line. However, in all organisms, the accumulation of specific and random chromatin modifications in the germ line may be important in speciation, because these modifications could lead to reproductive isolation between populations. Heritable chromatin variations may also alter the frequency and distribution of classical mutations and meiotic recombination. Therefore, inherited epigenetic changes in the structure of chromatin can influence neo-Darwinian evolution as well as cause a type of "Lamarckian" inheritance. PMID- 2593686 TI - Parental hormone levels and mammalian sex ratios at birth. AB - I have previously suggested that parental levels of several hormones (gonadotrophin, oestrogen, testosterone) at the time of conception affect the sex of mammalian offspring (James, 1986, J. theor. Biol. 118, 427). In this note it is suggested that progesterone also has such an effect. Clutton-Brock & Iason (1986, Q. Rev. Biol. 61, 339) concluded that variation of sex ratio had been reasonably well established with a number of variables in a number of non-human mammalian species. In this note, discussion centres on the adequacy of my hypothesis to accommodate these and other data. The evidence now is strong that hormonal variation is associated with variation of sex ratio at birth in some mammalian species: in a few species (e.g. man and the vole) there is a strong presumption that the relationship is causal. However the same sort of cause apparently affects the sex ratio in opposite directions in different species: so it may be speculated that the same hormone has opposite effects on sex ratio in different species. PMID- 2593688 TI - Effect of villosity and distension on the absorptive and secretory flux in the small intestine. AB - The effects of villosity and distension on the absorptive and secretory flux in the small intestine were investigated theoretically in a simplified model. In the case of low epithelial permeability, villosity increases both fluxes by surface enlargement, but in the case of high epithelial permeability, this occurred only if the intervillous spaces are very narrow. Otherwise, the flux is reduced due to the intervillous diffusion resistance, which is more effective than the enlargement of the surface area in that case. Distension increases the fluxes due to the additional surface exposed, by opening the intervillous spaces. In the case of low epithelial permeability this increase exceeds that expected from the enlargement of the smooth inner cylindrical surface area. In the case of high epithelial permeability, however, the increase of the fluxes exceeds surface enlargement only in the first phase, just after opening the intervillous spaces. Otherwise, the increase of the flux is less, since the hindrance by the intervillous diffusion resistance is more effective than the increase of the smooth inner cylindrical surface area. In the intervillous spaces the concentration gradient is non-linear with the steepest slope at the entrance due to the permeation through the lateral surfaces of the villi. The gradient approaches linearity in the center of broad intervillous spaces and becomes steeper when the width decreases and the epithelial permeability increases. In rat small intestine broad intervillous spaces are formed at the front sides of the trapezoidal villi by the predominant circular distension. The diffusion resistance in these spaces and the increase of the supravillous diffusion resistance weaken the increase of the absorptive and secretory flux by distension, especially in the case of high epithelial permeability. PMID- 2593689 TI - A model for swimming unipolar spirilla. AB - A mathematical model employing slender body theory is constructed for a unipolar Spirillum volutans cell with the model cell allowed to move unconstrainedly in the fluid. The results are compared with observation and previous studies and the effects of varying cell dimensions are investigated. PMID- 2593690 TI - Rumer's rule and transformation in the context of the co-operative symmetry of the genetic code. PMID- 2593691 TI - Ways of wobble pairing are formalized with the co-operative symmetry of the genetic code. PMID- 2593692 TI - The "START" and "STOP" of the genetic code: why exactly ATG and TAG, TAA? PMID- 2593693 TI - [Physiopathology, diagnosis and treatment of burns]. PMID- 2593694 TI - [Nursing process for burn patients]. PMID- 2593695 TI - [Nursing an adult burn patient]. PMID- 2593696 TI - [Nursing of a child with burns during a shock stage]. PMID- 2593697 TI - [A learning experience in expansion of ADL of a patient with a fracture]. PMID- 2593698 TI - [Relieving the pain associated with body movements of a patient with systemic metastasis of nasopharyngeal cancer. An innovation in allowing the patient to sit up at meal time]. PMID- 2593699 TI - [Nursing of patients with respiratory, endocrine or metabolic diseases]. PMID- 2593701 TI - [Seemingly insignificant nursing actions as psychological support of patients]. PMID- 2593700 TI - [Basedow's disease]. PMID- 2593702 TI - [A young cancer patient and her private life as a new bride]. PMID- 2593703 TI - [Loneliness of homebound senior citizens]. PMID- 2593704 TI - [Attitude of health professionals. Technology or personality?]. PMID- 2593705 TI - [Overall understanding of the patient (1). An encounter with a patient]. PMID- 2593706 TI - [Errors in your nursing: assistance to aged patients during defecation and urination]. PMID- 2593707 TI - Royal College of Nursing: review of the year. PMID- 2593708 TI - Community care--shouldn't nurses take the lead? PMID- 2593709 TI - The NHS is our trump card--don't throw it away. PMID- 2593710 TI - A strategy for nursing. PMID- 2593711 TI - Trev said! or the life and times of Trevor Clay. Interview by Margaret Green. PMID- 2593712 TI - Mayo Clinic's hospital-based emergency air medical transport service. AB - Mayo Clinic's hospital-based helicopter transport service, which is staffed by a medical flight crew consisting of two critical-care nurses, was initiated in October 1984. To date, more than 2,500 patients with a wide range of life threatening conditions have been transported. As a quality-assurance tool, a computerized data collection system was initiated in 1986, and this report details a 3-year experience in air transport garnered prospectively. From 1986 through 1988, 1,701 flights were completed in response to 2,329 requests for transport. Overall, 10% of requests were declined because of weather. Of 1,727 patients transported, 94% were brought to the Mayo Medical Center for care. The categories of the patients were medical-surgical in 1,071 (62%), trauma in 553 (32%), and neonates in 103 (6%). Most transports (93%) originated from referral inpatient facilities or emergency rooms; the rest were scene flights or transports from Mayo to other facilities. The mortality rate among the 1,632 patients brought to the Mayo Medical Center was 16.3%. The mean distance transported was 77 miles for interhospital and 23 miles for scene flights. For both trauma and medical-surgical patients, the severity of illness was evaluated with use of recognized quantitative scoring systems. Prospective collection of data has proved useful in program administration, quality assurance, and clinical research. Mayo Clinic's hospital-based helicopter transport program has served as a logical extension of the institution's emergency-care capabilities in an effort to enhance the prehospital and interhospital care of the critically ill within the institution's referral area. PMID- 2593713 TI - Effect of long-term freezer storage, thawing, and refreezing on selected constituents of serum. AB - We determined the effect of long-term freezer storage and repeated thawing and freezing of serum on concentrations of electrolytes (sodium, potassium, calcium, and phosphate), enzymes (aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatine kinase), total protein, tumor markers (carcinoembryonic antigen and alpha-fetoprotein), and other substances. Vials (1 ml) of frozen serum from a single blood drawing from 40 women with no breast disease and 70 with benign breast disease were analyzed annually from 1983 to 1987. Blood had been obtained from 40 subjects in 1978, 40 in 1980, and 30 in 1983. Thawing and refreezing studies were done in two ways: (1) serum samples from 30 subjects with benign breast disease were thawed at weekly intervals for 6 weeks and (2) serum samples from 30 patients with stage IV breast cancer were analyzed for alpha-fetoprotein and carcinoembryonic antigen, and serum specimens from 23 patients with benign breast disease and 7 control subjects were analyzed for lactate dehydrogenase and creatine kinase after thawing and keeping the samples at room temperature for up to 4 hours and then refreezing them. For measuring laboratory variability, duplicate samples were processed. Long-term storage (up to 10 years) and repeated thawing and refreezing did not affect the results of any tested constituents of serum. Although most measurements showed statistically significant variability over test cycles, these differences were thought to be due to laboratory variability. PMID- 2593714 TI - Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for role of sampling error. AB - Among 38 hearts from autopsies in which lymphocytic myocarditis contributed to death, 10 endomyocardial specimens from the apical septal aspect of each ventricle (760 specimens) and 6 slices of ventricular myocardium (228 slices) were evaluated for myocarditis by the Dallas criteria. For each case, the number of positive biopsy samples correlated well with the mean lymphocyte counts in biopsy tissues (P less than 0.0001) and the mean number of inflammatory foci per square centimeter in myocardial slices (P less than 0.001). Right ventricular biopsy specimens, however, were positive in only 63% of the 38 cases and 17% of the 380 specimens. Similarly, left ventricular biopsy tissues were positive in only 55% of the cases and 20% of the specimens. Sampling error was somewhat more prevalent among the 11 cases with isolated myocarditis than in the 27 with myocarditis and other illnesses. Even when 10 biopsy specimens per ventricle were evaluated, the frequency of false-negative results was 45% for the left and 37% for the right ventricle. Although myocarditis was noted in 68% of the 38 septal slices, it involved the subendocardium of the right ventricle (from which biopsy specimens are usually obtained) in only 24%. Because of the mild and focal nature of the inflammatory infiltrates and involvement of regions inaccessible to the bioptome, sampling error contributes appreciably to false-negative results in endomyocardial biopsy tissue from patients with myocarditis. Thus, when myocarditis is evaluated by biopsy alone, only positive findings are considered diagnostic. PMID- 2593715 TI - Chronic myelomonocytic leukemia: natural history and prognostic determinants. AB - A retrospective clinical review of 41 patients with chronic myelomonocytic leukemia revealed a median age of 66 years and a male:female ratio of 2.4:1. The disease was preceded by a myelodysplastic syndrome of a different subtype in 24% of the patients and transformed into acute leukemia in 24%. Splenomegaly was present in 54% of the patients and reached massive proportions in 24%. Chromosomal abnormalities occurred in 34% of those studied, most commonly in the younger age group; the most frequent were trisomy 8, monosomy 7, and deletions involving the long arms of chromosomes 20 and X. Polyclonal hypergammaglobulinemia was detected in 47% of the patients in whom serum protein electrophoresis was done. The median survival was 3 years. With use of univariate analysis, the statistically significant prognostic determinants were hemoglobin level, the "modified Bournemouth score," and bone marrow blast cell percentage. When these factors were subjected to a multivariate analysis, only bone marrow blast cell percentage was an independent prognostic determinant. Orally administered hydroxyurea controlled leukocytosis and splenomegaly in some patients without affecting the overall prognosis. PMID- 2593717 TI - Medicine's richness: survival of traditions. PMID- 2593716 TI - Intrathoracic lymphangiomatosis mimicking lymphangioleiomyomatosis in a young woman. AB - In this report, we describe a case of lymphangiomatosis that mimicked lymphangioleiomyomatosis in a 20-year-old woman. Lung biopsy specimens showed proliferation of anastomosing lymphatic channels in the visceral pleura and dilated peribronchiolar and septal lymphatic channels. During 8 years of follow up, this process behaved like lymphangioleiomyomatosis with reticulonodular infiltrates and worsening obstructive and restrictive changes evident on pulmonary function tests. PMID- 2593718 TI - The paradigm of medical education--it is time for a change. PMID- 2593719 TI - Human serum banks: a valuable resource--maybe. PMID- 2593720 TI - Convenient form for transfer of patients from nursing home to hospital. PMID- 2593721 TI - Surgical pathology of the pulmonary valve: a study of 116 cases spanning 15 years. AB - The gross surgical pathologic features of the pulmonary valve were reviewed in 116 patients (63 male and 53 female) who had undergone a cardiac operation with pulmonary valve excision at our institution during the period 1973 through 1987. Although the mean age was 12 years, subjects ranged in age from 3 months to 73 years, and 25 patients, including 19 with congenital heart disease, were older than 20 years of age. Among 105 patients who had pure pulmonary stenosis, 61 (58%) had tetralogy of Fallot, 18 had isolated pulmonary stenosis, 23 had other congenital cardiac anomalies, and 3 had carcinoid heart disease. Five patients had pure pulmonary regurgitation (four with tetralogy and one with infective endocarditis), and four had combined pulmonary stenosis and regurgitation (two with congenital cardiac anomalies and two with carcinoid heart disease). In two patients, the valve was neither stenotic nor regurgitant. Thus, congenital heart disease accounted for 110 of the 116 cases (95%), and tetralogy of Fallot was the most commonly observed form (65 cases). Bicuspid pulmonary valve was the most common anomaly and was present in 58% of patients with tetralogy but in only 17% of those with isolated pulmonary stenosis. PMID- 2593722 TI - Respiratory bronchiolitis-associated interstitial lung disease and its relationship to desquamative interstitial pneumonia. AB - Respiratory bronchiolitis is a mild inflammatory reaction commonly noted in asymptomatic cigarette smokers. We reviewed 18 cases of respiratory bronchiolitis associated interstitial lung disease (RB/ILD), which had been diagnosed on the basis of clinical evaluation and open-lung biopsy. All patients were cigarette smokers. The sex distribution of the patients was approximately equal, and their mean age was 36 years. Chest roentgenograms showed reticular or reticulonodular infiltrates in 72% of the patients. Histologically, inflammation of the respiratory bronchioles, filling of the bronchiolar lumens and surrounding alveoli with finely pigmented macrophages, associated interstitial inflammation, and mild fibrosis were noted. In most patients, respiratory improvement ensued when they stopped smoking. Because of histologic similarities to desquamative interstitial pneumonia (DIP), the 18 cases of RB/ILD were compared with 36 cases of DIP. DIP tended to occur in older persons, caused more severe symptoms, displayed ground glass infiltrates on chest roentgenograms, was characterized by more severe interstitial disease on pulmonary function tests, and was often associated with progressive respiratory disease. PMID- 2593723 TI - Hypertension--an overview. AB - The contributions in this symposium address the causes of both essential and secondary hypertension, optimal diagnostic techniques, treatment regimens, and long-term management of the hypertensive patient through a continued-care program. The intended emphasis is on issues that will have practical use in patient assessment and evaluation of therapeutic options. In particular, our goal was to provide current information that could enhance the care of the hypertensive patient. PMID- 2593724 TI - Acute megakaryocytic leukemia. PMID- 2593725 TI - The operatively excised pulmonic valve--a forgotten entity. PMID- 2593726 TI - Duration and costs of AIDS hospitalizations in New York. Variations by patient severity of illness and hospital type. AB - This study uses the Severity Classification for AIDS Hospitalizations to examine and contrast the duration and costs of hospitalizations among 6,142 AIDS discharges from New York hospitals during 1985. Multivariate regression analyses of resource-use differences suggest that more severely ill AIDS patients have considerably longer stays and higher total charges, regardless of hospital type. Severity of illness alone accounts for most of the explained variation in hospital length of stay (LOS) and total charges. In contrast, other patient characteristics, such as gender, race, and reported drug use, are less important predictors of resource use. It was also found that public teaching hospitals serve somewhat more severely ill AIDS patients than those treated in private teaching hospitals. The study concludes that the AIDS severity classification facilitates interhospital comparisons of illness levels and variations in resource use. PMID- 2593727 TI - Alcohol use and later hospitalization experience. AB - As an indicator of hospitalization costs, the number of hospitalized days among 82,430 white and black adult health maintenance organization (HMO) members was studied. Baseline data were collected at health examinations from 1978 to 1982. Using all hospitalizations from 1978 to 1983 that were not related to pregnancy and that occurred after examination, multiple regression analyses for each race sex subgroup were controlled for alcohol use (eight categories), cigarette smoking (four categories), age (three categories), and period of observation. Estimates of hospital days associated with alcohol, age, and smoking were calculated for specific diagnostic categories and for all diagnoses by projecting observed days hospitalized of lifelong alcohol abstainers, persons less than 45 years old, and lifelong nonsmokers. Among men of both races, there was almost no increase in total hospital days associated with alcohol use when all levels of drinking were considered. Among women, because of the preponderance of lighter drinkers who had fewer hospitalizations, the overall percentage of total hospital days associated with alcohol was negative. Several trends were identified between alcohol use and hospital days for the diagnostic groups. Most notable were a deficit of hospital days for circulatory system problems and an excess of hospital days for all neoplasms. In summary, in this population of prepaid health plan members, use of alcoholic beverages was only a minor factor in total hospitalization experience. PMID- 2593728 TI - Intraurban physician location. New empirical evidence. AB - This article addresses an issue of continuing interest to social scientists: the spatial distribution of physician services. Although there have been many studies of physician distribution across urban areas and states, there have been few studies, none recent, of physician distribution within urban areas. The paper begins with a review of studies that examine the determinants of intraurban physician location. Following the review the paper offers new estimates of the determinants of intraurban physician location using a maximum-likelihood procedure based on the Poisson distribution. Contrary to previous studies, the results imply that market forces do play a significant role in the spatial distribution of physicians. PMID- 2593729 TI - Reliability and validity of judgments concerning adverse events suffered by hospitalized patients. AB - To evaluate a process for identifying adverse events through review of medical records, multiple reviews of 360 medical records from two teaching hospital were performed. The data from these multiple reviews provided information about the validity and reliability of our two-phase review process. In particular, it was found that the initial phase, involving review of the medical records by medical record-room administrators using explicit criteria, was valid, with a sensitivity of 84% and negative predictive value of 92%. Results also showed that the second phase, involving judgments by physicians guided by an adverse event analysis form, was reliable (Spearman Brown Rm = 0.78, m = 2) and demonstrated construct validity when compared with a review by a set of senior physicians employing a different method of review (Kappa = 0.57). In addition, it was found that these cases classified as difficult to judge from causation were judged less reliable (Rm = 0.48, for difficult case, Rm = 0.65, for other cases, m = 1). These results indicate that a two-step review process of medical records can produce judgments about adverse events that are both reliable and valid. PMID- 2593730 TI - Underutilization of antihypertensive drugs and associated hospitalization. AB - The association of underutilization of drugs prescribed for the treatment of hypertension and acute-care hospital readmissions was evaluated. The data base consisted of computerized hospitalization records and computerized out-patient pharmacy records, checked by chart audit for validity. The number of days' supply of antihypertensive agents was estimated by dividing the quantity of drugs dispensed by the daily dose indicated by the prescription instructions. All patients had been admitted to an acute-care hospital during a 6-month period with the diagnosis of hypertension. Following discharge from the hospital, drug utilization and readmission status were determined for a minimum of 1 year. The drug compliance of a group of patients who were readmitted to the hospital was compared with the patients who were not readmitted. The readmitted group had a significantly higher ratio of days when they were without any antihypertensive agents relative to the length of time in the study. There were no statistically significant differences in demographic features or blood-pressure levels between the patient groups. These findings indicate that underutilization of antihypertensive drugs may be associated with hospitalization, which could be prevented if patients had complied with their medication schedules. PMID- 2593731 TI - Evaluating managerial efficiency of Veterans Administration medical centers using Data Envelopment Analysis. AB - This study applied the methodology of Data Envelopment Analysis (DEA) to the set of VA medical centers to evaluate their relative managerial efficiencies. Each VAMC was viewed as a producer of multiple outputs and a consumer of multiple inputs. DEA uses linear programming to identify resources that were underutilized and services that were inefficiently produced. Managerial strategies based on the dual variables were constructed to indicate the manner in which inefficient VAMCs may be made efficient. The analysis showed that relative inefficiency existed in about one third of the VAMCs nationwide. Elimination of this inefficiency would save the VA over $300 million annually on personnel, equipment, drugs, and supplies, without reducing the level of services provided. A subsequent analysis of co-variance revealed that VAMCs affiliated with a university were generally less efficient than those without such an affiliation. A similar finding was obtained for larger VAMCs relative to smaller medical centers. In neither case, however, should these results be construed to imply that VAMCs should terminate their university affiliations or that VAMCs should be made smaller since factors other than relative efficiency are clearly as or more important in such decisions. PMID- 2593732 TI - [Something for Sweden? Quality assurance and effectiveness of health care protected by law]. PMID- 2593733 TI - [Quality assurance of health care in the USA--a look into the 90's?]. PMID- 2593734 TI - [Dietary treatment of hyperlipidemia]. PMID- 2593735 TI - [A simple method of treating Colles' fracture is considerate of the patient]. PMID- 2593736 TI - [Oxidation of LDL and cholesterol is an important aspect of atherosclerogenesis]. PMID- 2593738 TI - [What is right? What is wrong? Where should the limit be drawn?]. PMID- 2593737 TI - [Are sick physicians treated worse than other patients?]. PMID- 2593739 TI - [The first case of generalized histoplasmosis in a patient with AIDS in Sweden]. PMID- 2593740 TI - [Every fourth inhabitant of Gotland smokes. The majority wish smoke-free public facilities]. PMID- 2593741 TI - [CRST syndrome--a type of progressive systemic sclerosis]. PMID- 2593742 TI - [Itching skin changes after a holiday abroad]. PMID- 2593743 TI - [A pilot study shows: a survey of surgical complications can diminish the risk--a primary study has been started]. PMID- 2593744 TI - [A deficient intervention against risk factors among patients with coronary vascular surgery]. PMID- 2593745 TI - [Treatment of spasticity using an intrathecal infusion of baclofen]. PMID- 2593746 TI - [Rett syndrome--from a healthy infant to a disabled woman]. PMID- 2593747 TI - [Frequent sick-listing during pregnancy in spite of a well-functioning parenthood insurance system]. PMID- 2593748 TI - [Contradictory views at meeting of experts: support for the hypothesis on increased risk of breast cancer after prolonged use of oral contraceptives]. PMID- 2593749 TI - [Human genome studies--the book of life to be completed by the turn of the century?]. PMID- 2593750 TI - [A patient with renal calculi under false premises--again]. PMID- 2593751 TI - [Regaine again. A carcinogen?]. PMID- 2593752 TI - [Analysis of cardiolipin antibodies should be done before penicillamine treatment]. PMID- 2593753 TI - [Is there any connection between residence characteristics and low birth weight?]. PMID- 2593754 TI - [Every other Swedish heterosexual man with HIV became infected during a stay abroad]. PMID- 2593755 TI - [Early transplantation is recommended in metabolic diseases]. PMID- 2593756 TI - [Risk of miscarriage after chorionic biopsy is probably not higher than after amniocentesis]. PMID- 2593757 TI - [Hypertriglyceridemia--a common, often overlooked blood lipid disorder]. PMID- 2593758 TI - [DNA diagnosis of mitochondrial diseases is now possible]. PMID- 2593759 TI - [Identification of the cystic fibrosis gene. Better therapeutic methods can be expected]. PMID- 2593760 TI - [A preliminary report to the Committee of Alternative Medicine: it is impossible to predict the effect of magnetic therapy. More studies on fractures with prolonged wound healing are needed]. PMID- 2593761 TI - [Acute hemorrhagic leukoencephalitis is often misdiagnosed as herpes encephalitis]. PMID- 2593762 TI - [Successful surgical treatment of acute massive pulmonary embolism]. PMID- 2593763 TI - [Thalidomide--a possible alternative as an immunomodulating agent]. PMID- 2593764 TI - Effects of intraarterial, intravenous, and intraluminal neurotensin on canine ileal sodium and water absorption and blood flow. AB - Neurotensin is a regulatory peptide which is found primarily in the ileum and is secreted into the blood and lumen. The physiologic effects of neurotensin are uncertain but in certain pathologic states neurotensin increases to levels which can have effects on many organs. The effects of intravenous, intraarterial and intraluminal neurotensin (0.075-7.5 micrograms/min) on fed canine ileal sodium and water fluxes, potassium secretion, and blood flows were studied. Intravenous and intraarterial infusion of neurotensin increased net sodium, potassium, and water secretion, due to increased secretory fluxes, and increased hematocrits. Intraarterial neurotensin was not more effective than intravenous neurotensin except for stimulating potassium secretion. Neurotensin increased potassium secretion at 0.075 micrograms/min IA, increased sodium and water secretion at 0.75 micrograms/min IA and IV, and increased hematocrit at 7.5 micrograms/min IA and and IV. Total and absorptive site blood flows and arterial and venous pressures were not changed. Intraluminal neurotensin had no effects at any infusion rate. Neurotensin can increase potassium secretion at physiologic levels by a local effect and can increase sodium and water secretion at high physiological-pathological levels through a hormonal mechanism. The secretion is not dependent on cardiovascular changes. PMID- 2593765 TI - Brief maternal deprivation of rats reduces hepatic mixed function oxidase activities. AB - Deprivation of pups from mother and sibs for 3 min daily from day 5 to day 41 of life reduced activities of 4 hepatic mixed function oxidases (MFO) expressed per mg protein in male rats compared to unhandled control rats. These decreases, though generally small, 22.4% and under, reached statistical significance for the substrates aminopyrine, benzphetamine and ethoxycoumarin. This handling procedure did not consistently affect the inductive response to phenobarbital. Previously ignored as a source of variability in response to xenobiotics, "handling" appears from these results to merit further investigation as such a factor in uninduced rats. Differences among rats in "handling" could contribute to large day-to-day variations in their metabolism of xenobiotics. PMID- 2593766 TI - Norepinephrine triggers medullar epinephrine depletion during normoglycemia. AB - Our experiments did show that chronic 12 hours administration of norepinephrine (NE) to rats by means of subcutaneously implantable retard tablets, led to a highly significant epinephrine (E) depletion of the adrenal medulla during normoglycemia. The expected rise of free plasma NE at 6 and 12 hours was accompanied by increased free plasma E values at 12 hours. At this very time point the liver contents of glycogen and free intracellular glucose showed their most pronounced decrease. Since at 12 hours both liver glycogen and medullar E values were at their lowest, a second experiment was performed to examine a possible causal relationship. In order to curb the breakdown of liver glycogen, rats were force fed with 50% glucose solution 9 hours after NE tablet implantation. Glucose feeding not only caused a much less pronounced liver glycogen fall at 12 hours, but, at the same time also prevented E depletion of the adrenal medulla. These observations suggested that rapid fall of liver glycogen and/or liver intracellular free glucose might be the trigger for medullar E depletion, even before hypoglycemia. PMID- 2593767 TI - Saliva and serum cortisol dynamics following intravenous dexamethasone in normal volunteers. AB - In order to further explore the utility of saliva cortisol as an accurate measure of adrenal steroid production, dexamethasone (DEX) and saline were administered intravenously at 0800h to eight normal male volunteers in a randomized design, and the effects on serum and saliva cortisol concentrations were measured at hourly intervals from 0800h-2300h. Saliva cortisol values were highly correlated to serum cortisol levels within-subjects under both conditions (r = 0.78, p less than 0.025), however correlations were reduced in the DEX day sample pairs. Across-subject correlations at each time point were considerably more variable, reflecting interindividual differences in the saliva to serum cortisol ratios. No consistent time lag of saliva cortisol values in response to serum cortisol fluctuations was observed. These data suggest that saliva cortisol is an excellent index of changes in adrenal production of cortisol over time within individuals; however, it also suggests that salivary cortisol measures have less usefulness in comparing values across groups of individuals. PMID- 2593768 TI - Distribution and molecular forms of glucagon-like peptide in the dog. AB - Using glucagon-like peptide-1 N-terminus and C-terminus directed antisera, we investigated concentration and molecular forms of GLP-1 immunoreactivity (IR) in extracts of various tissues of the dog. GLP-1 IR measured with C-terminus directed antiserum R2337 (GLP-1 IR-CT) was high in the ileum, appendix, jejunum, colon, and gastric fundus and body. GLP-1 IR measured with N-terminus-directed antiserum R1043 (GLP-1 IR-NT) was high only in the pancreas, and gastric fundus and body. Only GLP-1 IR-CT was found in the hypothalamus, thalamus and medulla oblongata. No immunoreactive materials were detected in the liver, spleen and kidney. Gel-filtration with Sephadex G-50 showed two peaks of both GLP-1 IR-CT and GLP-1 IR-NT, at 10kd and at the position of GLP-1 (1-36 amide) in the pancreatic extract, and one peak at 10kd in the stomach extract. Ileal extracts showed 3 peaks of GLP-1 IR-CT at 10kd, at the position of GLP-1(1-36 amide) and GLP-1(7-36 amide), respectively, but GLP-1 IR-NT was coeluted with GLP-1(1-36 amide). Hypothalamic extracts showed a single peak at the position of GLP-1(7-36 amide). These results suggest that processing of preproglucagon differs in different organs, and that the main GLP-1-related products are a large molecular form and GLP-1(1-36 amide) or GLP-1(1-37) in the pancreas, and GLP-1(7-36 amide) or GLP-1 (7-37) in the ileum and hypothalamus. PMID- 2593769 TI - Mitogenic activation of the human lymphocytes induce the release of proenkephalin derived peptides. AB - Several reports indicate that enkephalins participate in lymphocyte proliferation and several events of the immune response. It has been proposed that peptides involved in these processes may originate in the nervous system or endocrine glands. We have found that human peripheral blood lymphocytes (PBL) activated with a mitogenic agent contain and release proenkephalin derived peptides. The kinetics of met-enkephalin and cryptic products of proenkephalin in PBL activated with phytohemaglutinin (PHA) were studied. Peptides were released to the supernatant of stimulated PBL, reaching the highest values after 18 to 24 hours. The material secreted corresponds to high, intermediate and low molecular weight peptides derived from proenkephalin, displaying met-enkephalin and synenkephalin (proenkephalin 1-70) immunoreactivity. Therefore, an intrinsic lymphocytic proenkephalin system is induced by PHA and may play an important role in the regulation of the immune response. PMID- 2593770 TI - Toxoplasmosis: effectiveness of enzyme immunoassay screening. AB - The effectiveness of IgG enzyme-linked immunosorbent assays as serological screening tests for Toxoplasma gondii infection was investigated in three Scottish hospital laboratories. Three assays--two commercial and one produced by the Scottish Toxoplasma Reference Laboratory--were investigated. There was little difference in the sensitivity of the three tests (86-91%), but one of the commercial tests was markedly less specific. The performance of the more specific assays was improved by adjustment to an eight international unit per ml threshold. PMID- 2593771 TI - Solvent systems for thin layer chromatography of biological dyes. AB - Thirty-nine dyes were subjected to thin layer chromatography to evaluate eight different solvent systems. The results obtained were analysed by dye class following assessment in daylight and ultra violet light. N-butanol: acetic acid: water (40:10:50) gave optimum separations of dyes viewed in visible light. Although n-butanol: ethanol: water (90:10:10) gave slightly better results for fluorescing compounds, material was frequently left at the start point with this solvent. PMID- 2593772 TI - Gelatin particle agglutination assay for HIV antibodies: a rapid, economical modification with increased sensitivity. AB - Modification of a commercial gelatin particle agglutination assay for anti-HIV reduces the test time to 30 min, increases the sensitivity sevenfold without any prozoning, and maintains specificity while cutting the cost of the test by 90%. The modification involves a tenfold dilution of the gelatin particles, which are added to a dilution of test serum in a 'V' well standard microplate. After incubation, plates are centrifuged briefly and allowed to stand at an inclination of 70 degrees until positive and negative reactions are clearly distinguishable within approximately 15 min. PMID- 2593774 TI - Reference values terminology. PMID- 2593773 TI - MANAGER: a multi-user computer scheme for management of laboratory staff working hours. AB - To administer a flexible-working-time system in a busy medical microbiology department, without increased administrative workload, a set of programs was produced for computer monitoring of staff time-keeping records. The programs- initially written to facilitate management and minimise clerical work, and extended to encompass all staff absences--are collectively called MANAGER. They allow efficient management of working hours and staff absences, using a multi user laboratory computer. The programs were all written in MUMPS and evolved in house, but could be developed for any multi-user laboratory computer system. PMID- 2593775 TI - Storage of hepatitis B surface antigens. PMID- 2593776 TI - Proportions of haemoglobin S in sickle-cell trait. PMID- 2593777 TI - Urine screening for leucocytes and bacteria by dipstick and reflectance spectrophotometry. AB - In order to develop a rapid and reliable method for screening large numbers of urines for leucocytes and bacteria a dipstick method was used with colorimetric reading of colour changes with a reflectance spectrophotometer. One thousand consecutive urine specimens were tested by that method using a single dipstick for leucocyte esterase, nitrite, blood and protein in parallel with routine methods for enumeration of leucocytes by microscopy and quantitative culture for bacteria. Results of the four dipstick tests taken together had predictive values of 83.7% for a positive test for evidence of infection and 97.2% for a negative result. The false negative rate was 1%. Of the 191 urines with a significant bacteriuria (greater than 10(5) organisms/ml), 10 were false negatives by dipstick testing, representing 5% of all infected urines. Elimination of the need for culture on specimens that were negative by all four tests would reduce the workload by 36%. PMID- 2593778 TI - Diurnal rhythm of vasopressin mRNA species in the rat suprachiasmatic nucleus: independence of neuroendocrine modulation and maintenance in explant culture. AB - Vasopressin mRNA in the suprachiasmatic nucleus (SCN) of the rat brain exhibits diurnal variation in poly(A) tail length; a single species of mRNA identical in size to that in other hypothalamic nuclei is expressed in the light phase of the daily cycle whereas a second, smaller species is expressed in the dark phase. We have investigated the neuroendocrine factors which may regulate this rhythm by comparing vasopressin mRNA size with Northern analysis of RNA extracted from SCN tissue taken at 09.00 h (light phase) and 21.00 h (dark phase). The consistent rhythmic variation observed in normal male rats was not modified in either adrenalectomized or castrated animals or in ovariectomized female rats. The rhythm was also not disrupted following treatment with the serotonin-depleting agent parachlorophenylalanine, or following treatment with either melatonin or the benzodiazepine, triazolam. We next investigated whether the daily pattern of expression was maintained in isolated SCN. Microdissected blocks containing the paired SCN were explanted into culture at various times of the day for a period of 4 h. Vasopressin mRNA extracted from light phase cultures (11.00-15.00 h) exhibited no size change from control SCN mRNA taken at either 11.00 h or 15.00 h. In contrast, mRNA from cultures maintained over the period 16.00-20.00 h (lights off: 18.00 h) exhibited a marked size difference from 16.00 h controls, being similar to the smaller species observed in 20.00 h controls. Similarly, vasopressin mRNA from cultures maintained over the period 05.00-09.00 h (lights on 06.00 h) was similar in size to 09.00 h controls and contrasted to the pattern of expression observed in 05.00 h controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593779 TI - Regional distribution of neuropeptide Y mRNA in postmortem human brain. AB - The distribution of messenger RNA encoding neuropeptide Y (NPY) was studied in 11 different postmortem human brain regions using in situ hybridization histochemistry, and RNA blot analysis. In situ hybridization data revealed that the highest numerical density of labeled cells corresponded to neurons in accumbens area, caudate nucleus, putamen, and substantia innominata. Significantly fewer NPY mRNA-containing neurons were found in frontal and parietal cortex, amygdaloid body and dentate gyrus. No NPY mRNA-containing cells were found in substantia nigra. NPY mRNA-positive neurons from all regions studied showed relatively similar labeling, as revealed by computerized image analysis. Blot analysis showed an approximately 0.8 kb NPY mRNA in all brain regions studied, except in substantia nigra and cerebellum. Densitometric scanning of the autoradiograms revealed levels of NPY mRNA in the following order: putamen greater than caudate nucleus greater than frontal cortex (Brodmann areas 4 and 6) greater than temporal cortex (Brodmann area 38) greater than parietal cortex (Brodmann areas 5 and 7) greater than frontal cortex (Brodmann area 11). Hence, although NPY mRNA is widely distributed in neurons of the human brain large regional variation exists, with the highest expression in accumbens area and parts of the basal ganglia. PMID- 2593780 TI - Expression of the gene encoding the beta-subunit of S-100 protein in the developing rat brain analyzed by in situ hybridization. AB - To investigate patterns of expression of the gene encoding the beta-subunit of S 100 protein during development of the rat brain we have used Northern blotting and in situ hybridization histochemistry. During late prenatal development beta-S 100 mRNA was observed first in the germinal zone lining the 4th ventricle. In the postnatal cerebellum this mRNA accumulated primarily in Bergmann glia and astrocytes of the deep white matter. In the hindbrain, expression of S-100 mRNA increased steadily in specific regions during the first postnatal week while levels remained low in more anterior brain regions. By the end of the second postnatal week, a dense punctate signal was distributed throughout the midbrain and hindbrain. Expression in forebrain, first observed at E18, was confined to cells lining the ventricle until the second postnatal week when accumulation of mRNA was observed in specific regions of the hippocampus, neocortex and olfactory bulb. The adult brain pattern of beta-S-100 mRNA distribution is attained during the third postnatal week. These results demonstrate a caudal-rostral gradient in expression of the beta-S-100 gene during rat brain development, as well as pronounced regional differences which may reflect the differentiation of subpopulations of astrocytes. PMID- 2593781 TI - Changes of proenkephalin and prodynorphin mRNAs and related peptides in rat brain during the development of deep prepyriform cortex kindling. AB - The effects of deep prepyriform cortex (DPC) kindling on the amount of proenkephalin and prodynorphin mRNAs, Met5-enkephalin (ME) and dynorphin (DYN) in rat brain were examined. Animals received electrical stimulation of the DPC until two consecutive stage 2 seizures (S2) or stage 5 seizures (S5) were attained. The proenkephalin mRNA and ME contents in the entorhinal cortex were increased 24 h after S2 and also 5 min and 24 h post S5. In the hippocampus, the proenkephalin mRNA level was reduced 24 h after S2 but increased 5 min and 24 h after S5. Elevated hippocampal ME concentration was observed 24 h after S2 and S5. Similarly, the ME level in the frontal cortex was increased 24 h after S2 and S5 but the proenkephalin mRNA content was only elevated at S5. In the striatum, the proenkephalin mRNA level was slightly increased 24 h after S2 and S5, but no change in ME content was found. The amount of prodynorphin mRNA in the hippocampus was attenuated only at 24 h after S5, whereas DYN concentration was reduced 5 min after S5. No change in striatal DYN concentration was observed despite a slight elevation of prodynorphin mRNA 24 h post S2 and S5. Six weeks after the last seizure, no difference in ME and DYN was found between kindled and control animals. These findings indicate that the enkephalin-containing perforant pathway in the entorhinal cortex-hippocampal region is particularly sensitive to electrical stimulations applied to the DPC. Its role and importance in the development of kindling are discussed. PMID- 2593782 TI - Prepro-VIP and preprotachykinin mRNAs in the rat dorsal root ganglion cells following peripheral axotomy. AB - Using in situ hybridization histochemistry, we examined the expression of prepro vasoactive intestinal polypeptide (VIP) mRNAs and preprotachykinin (PPT) mRNAs which coded for substance P (SP) in the rat dorsal root ganglion (DRG) following spinal nerve transection. VIP mRNAs increased dramatically in the DRG neurons after transection of the peripheral branch of the spinal nerve (sciatic nerve), whereas PPT mRNAs showed a gradual decrease for a few weeks. Dorsal rhizotomy or axotomy of the central branch of DRG cells had little influence on VIP-mRNAs and no effect on PPT mRNA expression. These results demonstrated an activation of VIP biosynthesis in the DRG neurons due to axotomy of the peripheral branch, which was opposite to the reaction of PPT mRNA to the same treatment. PMID- 2593783 TI - [The role of paramedical personnel in detecting the early clinical forms of cerebral circulatory insufficiency]. PMID- 2593784 TI - [The treatment of myocardial infarct by sorption methods]. PMID- 2593785 TI - [Laser therapy in the combined treatment of the trophic disorders in the postthrombophlebitis syndrome]. PMID- 2593786 TI - [The education of sick children in the family and in the treatment institution]. PMID- 2593787 TI - [Aromatic baths]. PMID- 2593788 TI - [X-ray photographic materials]. PMID- 2593789 TI - [The skin and its care]. PMID- 2593790 TI - [Spring adonis (Adonis vernalis L.)]. PMID- 2593791 TI - [Deontology in the birth of children with developmental defects]. PMID- 2593792 TI - [Plants in the diet]. PMID- 2593793 TI - [Vegetables in human nutrition]. PMID- 2593794 TI - Opsonic requirements and interaction of Haemophilus influenzae with human polymorphonuclear neutrophil leucocytes studied by luminol-enhanced chemiluminescence. AB - We have used human polymorphonuclear leucocyte (PMNL)-dependent chemiluminescence (CL) to study bacteria opsonised with those factors in serum which are reported to be important in opsonisation of H. influenzae, and to determine whether alteration of various surface characteristics of H. influenzae influence those CL responses by PMNL. Although complement plays a role, immunoglobulin and a heat labile factor(s) were found to be the principle stimulants of PMNL-dependent CL when H. influenzae was opsonised in pooled normal human serum. Acquisition of capsule (serotype a,b,c,e, or f) by an uncapsulated strain significantly (P less than 0.001) reduced its ability to stimulate PMNL-dependent CL, but the type of capsule did not discriminate between the strains in this regard. Surface-adherent capsule inhibited PMNL-dependent CL stimulation more than capsular material released into the supernatant. Altering the lipooligosaccharide composition of the bacterial cell wall also affected PMNL-dependent CL stimulation independent of capsule. We conclude that, although surface characteristics of H. influenzae influenced its ability to stimulate PMNL-dependent CL, these experiments provide no evidence to support the hypothesis that the increased virulence of serotype b capsulated strains compared with other capsulated types could be explained by any specific ability to avoid opsonisation. PMID- 2593795 TI - Microcirculatory responses to vascular washout following ischemia. AB - This study examined the microcirculatory alterations in the hindlimb of the rat caused by ischemia and vascular washout with lactated Ringer's solution. Experimental groups consisted of innervated and denervated animals, each subjected to 2 hours of hindlimb ischemia. The ischemic period was then followed by either vascular washout or no washout prior to reperfusion. The cutaneous capillary blood flow was measured using laser Doppler velocimetry. The results demonstrated a substantial increase in early reperfusion flow above baseline in the innervated groups, more apparent in the group subjected to vascular washout. In all cases where there was elevated early flow, later flow levels were decreased. The results and proposed mechanisms of the response are discussed. PMID- 2593796 TI - Single pedicle microvascular transfers of the serratus anterior and latissimus dorsi muscles in rats. AB - In the rat, the serratus anterior and latissimus dorsi muscles receive axial vascular pedicles from the thoracodorsal artery. This anatomy was confirmed by dissections, and 10 microvascular transfers of the latissimus-serratus flap on a common pedicle were performed with a 90% success rate. The flaps had an average weight of 1.8 g. This flap is a reliable small animal model for microvascular muscle transplants and contains sufficient tissue to be used in multiple biochemical assays. PMID- 2593797 TI - Long-term histological changes in 1 millimeter polytetrafluoroethylene (Gore-Tex) prosthetic arterial grafts. AB - Vein grafts are used extensively to repair blood vessels. However, when suitable vein segments are unavailable, alternative graft materials must be used. This study tested the suitability of 1 mm diameter polytetrafluoroethylene (PTFE) grafts for small-calibre arterial replacements. Grafts of 4 mm length were inserted microsurgically into the iliac arteries of 26 rats. The grafts were removed between 3 and 22 months postoperatively and examined with light microscopy and scanning and transmission electron microscopy (SEM:TEM). Anastomotic intimal hyperplasia was minimal, consisting of a few smooth muscle cells extending 100-200 microns onto the graft. The rest of the PTFE was covered with endothelium. In a few isolated areas, there was a subendothelial layer of smooth muscle, 2-10 cells thick. The short segments used in this study were highly successful, with an overall long-term patency rate of 80%. These grafts showed no evidence of excessive neo-intimal hyperplasia. PMID- 2593798 TI - New canine model for free jejunal graft studies. AB - The need to more fully understand the function and physiology of the free jejunal graft prompted us to develop a new canine model. Twelve dogs were used to transplant a free jejunal graft in the neck with proximal and distal stomas exteriorized to the skin. The techniques used, complications encountered, and the potential for acute and chronic studies with this animal model are presented. PMID- 2593799 TI - Phrenic nerve transfer for brachial plexus motor neurotization. AB - We report a series of 164 patients who underwent phrenic neurotization to elements of the brachial plexus with root avulsion injuries. Recipient nerves included musculocutaneous nerve in 125 patients (78 direct neurotizations and 48 with intervening autograft), median nerve in 10 patients, and a variety of other nerves in 28 patients. Sixty-five patients presented a follow-up period of 2 or more years. Of this group, 55 patients (84.6%) achieved a recovery of M-3 or better. We observed no long-term deleterious effects on respiratory function. PMID- 2593800 TI - Experimental peripheral nerve repair: environmental control directed at the cellular level. AB - This study recognizes recent advances in the understanding of the anatomy and physiology of peripheral nerves at the cellular level. It has reproduced study conditions originally advocated by de Medinaceli and coworkers, with modifications. Eighty-four rats were divided into three groups. Group A underwent sciatic nerve transection and standard perineurial repair. Group B nerves were frozen, severed with a vibrating blade, and reconnected by tubulization with a rubber cuff while bathed in solutions designed to inhibit Ca++-calmodulin activation, maintain colloid osmotic pressure, and mimic ambient electrolytic conditions. Group C underwent a similar procedure as group B, with the rubber cuff replaced by a polyglycolic acid mesh. All animals were randomized and evaluated functionally in terms of a sciatic index. By post-operative day 225, animals of group A recovered 37% of function, group B recovered 74%, and group C recovered 67%. Compound action potential recordings revealed a velocity recovery of 41% in group A, 70% in group B, and 81% in group C. Microscopic evaluation provided evidence for corresponding structural improvement. This new method of nerve repair is uncomplicated, relatively inexpensive, and easily adaptable to other animal models. PMID- 2593801 TI - Emergency knee joint salvage utilizing a free musculofasciocutaneous flap based on the anterior tibial artery: case report. AB - A young adult male presented with a traumatic amputation at the upper third of his left leg and an extensive soft tissue loss around his left knee. A free musculofasciocutaneous flap was elevated on the anterolateral part of the amputated segment and transferred to the soft tissue defect around the proximal left tibia in order to avoid an above-knee amputation. The entire flap depends on the anterior tibial artery for its blood supply. The anatomy of the flap is outlined. The importance of the musculocutaneous blood supply as well as the presence of an extensive fascial component make the flap very reliable. An 18 month follow-up period showed a uniformly well-contoured soft tissue coverage and an optimal functional result. PMID- 2593802 TI - Foot salvage in arteriolosclerotic and diabetic patients by free flaps after vascular bypass: report of two cases. AB - Vascular bypass has been a successful procedure for the salvage of ischemic limbs. Amputation after vascular bypass procedures alone is common when extensive ulceration, osteomyelitis, or bone-tendon exposure is present, especially in the diabetic patient. We report two patients in whom the foot was salvaged by microsurgical free flap after revascularization with bypass grafting. Both patients are diabetic who presented with severe arteriolosclerotic foot, associated with extensive ulceration as well as bone and tendon exposure. PMID- 2593803 TI - "Window technique" for approximation during end-to-end vascular anastomosis. AB - A new, simple, and atraumatic technique for prevention of tension at the site of an anastomosis during end-to-end vascular anastomoses without using an approximator clamp is described. PMID- 2593804 TI - An easy and safe way to dress limb flaps in the dog. AB - When a flap is elevated in a human, the patient is usually managed with bed rest. The same conditions are impractical in dogs. Sometimes a flap in the dog must be protected from the dog itself by applying a special cast or a bucket on the head. An easy, safe, inexpensive, and quick method to dress the dog, by simply applying hot pepper into the dressing, is described. PMID- 2593805 TI - Free-flap reconstruction of large head and neck defects in the elderly. AB - Advanced-stage and recurrent malignancies of the head and neck place severe demands on both the surgical team and the patient. Marked alterations in cosmesis and function are to be expected following major ablative surgery. The use of free tissue transfer with microvascular anastomoses has provided the head and neck surgeon the freedom to resect these lesions aggressively and to provide the patient with improved cosmesis, function, and protection of vital structures. A series of six cases involving patients at The University of Alabama at Birmingham over the past year is presented. PMID- 2593807 TI - [Women of science in the Third World]. PMID- 2593806 TI - [Nobel Prizes in Medicine 1988: pioneers in drug research]. PMID- 2593808 TI - [Advances in erythropoietin]. PMID- 2593810 TI - [The importance of adenosine deaminase in pleural effusion]. PMID- 2593809 TI - [Asthma mortality in Argentina. Why is it so high?]. PMID- 2593811 TI - [Nifurtimox and benznidazole inhibit DNA and protein synthesis in rat hepatocytes]. PMID- 2593812 TI - [Organic changes in rabbits and rats in thiometon poisoning. II. Relation between ECG curve changes in rabbits and rats and cholinesterase inhibition and lysosomal hydrolase activation in acute thiometon poisoning]. AB - ECG records were analysed in rabbits and rats administered with Intration. Similarly, analysed were ECG records in the animals which, apart from the insecticide, received PAM and Toxobidin. On administration of the pesticide, cardiasthenia and lowered tension of R and R waves, prolonged duration of PQ segments and QT intervals were found. In addition, some animals exhibited the first-degree a-v block and second-degree block in the form of Wencke-bach's period. On administration of PAM and Toxobidin ECG curve elements were largely normalized. This implies that some of the ECG impairments are reversible, which may be accounted for by inhibition and reactivation of AChE and AhE. On the other hand, ECG records did not demonstrate myocardial necrosis in pesticide-poisoned patients. PMID- 2593813 TI - [Analysis of the effects of physico-chemical factors on the stability of lead and mercury levels in biological specimens. I. Biological specimens with the addition of Pb and Hg standards]. AB - For the analysis of the process of precipitation and adsorption in the walls of polyethylene and glass vessels in which biological specimens containing mercury and lead were stored, the techniques of scanning electrone microscopy and X-ray microanalysis were applied. It was observed that the losses of: --lead in stored urine specimens were mainly due to precipitation, --mercury in stored urine specimens occur, among others, through adsorption on vessels' walls. X-ray microanalysis may also facilitate determination of the chemical composition of micro-structural fragments deposited on the surface of vessels. PMID- 2593814 TI - [Effect of Polfos on the bleeding time. III. Changes in various parameters of the circulatory system]. AB - The influence of Polfos on the blood pressure in rats was measured by direct and indirect methods. The influence of this pesticide on the heart rate was also examined. Two hours after Polfos administration an increase in blood pressure and a decrease in heart rate were observed. In the late phase of Polfos-intoxication no changes in the cardiovascular system were found. The results show that prolonged bleeding time in the initial phase of the intoxication might depend on its influence on the cardiovascular system in rats. PMID- 2593815 TI - [Internal ear damage in vibration syndrome caused by local vibration]. AB - Unlike with the vibration syndrome caused by general vibration whose clinical picture may exhibit internal ear impairments in the of hearing losses and vestibular disturbances, similar lesions in the vibration syndrome due to local vibration have not been confirmed explicitly. For better explanation of this issue, analysed were the results of audiometric and electronystagmographic (ENG) tests in a group of 40 otologically healthy++ men, in whom during 1986-1987 the angioneurotic vibration syndrome was diagnosed. The results were analysed considering subjects' age and duration of work in exposure; evaluation involved the increase in hearing thresholds for pure tones (audiometer Peters AP-6) and quantitative and qualitative changes in ENG records (electronystamograph Tonnies D-420 TS), calculating, among others, amplitudes and angular velocity of nystagmus slow phase. In 75% of subjects (30 persons) sensorineural hearing losses of different degree were found, mostly within the 3000-8000 Hz range, demonstrating a directly proportional dependence on the length of employment. Symptoms of vestibular disturbances in ENG records were detected in 57.2% (23) persons with marked predominance of the cases of vibration exposure over 10 years. The authors analyse mechanisms of the development of internal ear impairments in result of local vibration and concomitant noise. PMID- 2593816 TI - [Structure of antero-posterior spinal curvatures in manual workers in relation to their occupations]. AB - The authors examined spondylometrically 1572 (648 men and 924 women) labourers of the FAEL factory in Zabkowice Slaskie. Sixteen spondylometric features were taken into account. The results were analysed by generally adopted statistical methods. Calculations were made for men and women separately. The subjects were divided into those performing their work in sitting and standing positions. Furthermore, the workplace of each worker was examined. The studies demonstrated a considerable correlation between the antero-posterior curvatures of the spine and specific workplaces. PMID- 2593818 TI - [A case of death after drinking of alcoholic solution of formalin]. PMID- 2593817 TI - [Levels of metabolites of selected chemical compounds in the urine of workers in pitch coke plant]. AB - In urine samples collected from pitch coke plant workers just before and after occupational exposure, differentiated concentrations of phenol (20.8-692.8 mg/dm3), p-cresol (51.8-590 mg/dm3), I-naphtol (4.9-63.7 mg/dm3) and benzo(a)pyrene (0.3-18.9 ug/dm3) have been found. The occurrence of enhanced concentrations of phenol in 10.1%, p-cresol in 31.9%, I-naphthol in 13.5% and benzo(a)pyrene in 72.8% of the test urine specimens collected prior to exposure points to a slow excretion of these metabolites of chemical compounds inherent in the work environment. Furthermore, the urinary level of the metabolites in particular coke plant workers points to different individual exposure. PMID- 2593819 TI - [Enteropathogens detected in healthy children in 3 low income communities, in Recife, State of Pernambuco, Brazil]. AB - Stools of 646 healthy children between zero and five years of age who live in 3 communities of slightly different economic levels and sanitary conditions were investigated for enteropathogenic Escherichia coli (EPEC), enteroinvasive E. coli (EIEC), Shigella and Salmonella. Cultures were positive for enterophatogens in 82 (12.69%) of the children. EPEC was the most frequent isolate (6.04%) followed by Shigella (4.18%) and Salmonella (2.17%). Invasive E. coli (EIEC) was detected only twice. According to our results, the frequency of isolation of enterophatogenic bacteria decreases where the economic level and sanitary conditions improve. The percentage of 12.69% positive cultures among normal children shows that the healthy carrier plays an important role in the dissemination and maintenance of the agents of the enteric diseases. PMID- 2593820 TI - Jatobal virus antigenic characterization by ELISA and neutralization test using EIA as indicator, on tissue culture. AB - A virus antigenic characterization methodology using an indirect method of antibody detection ELISA with virus-infected cultured cells as antigen and a micro virus neutralisation test using EIA (NT-EIA) as an aid to reading were used for antigenic characterization of Jatobal (BeAn 423380). Jatobal virus was characterized as a Bunyaviridae, Bunyavirus genus, Simbu serogroup virus. ELISA using infected cultured cells as antigen is a sensitive and reliable method for identification of viruses and has many advantages over conventional antibody capture ELISA's and other tests: it eliminates solid phase coating with virus and laborious antigen preparation; it permits screening of large numbers of virus antisera faster and more easily than by CF, HAI, or plaque reduction NT. ELISA and NT using EIA as an aid to reading can be applicable to viruses which do not produce cytopathogenic effect. Both techniques are applicable to identification of viruses which grow in mosquito cells. PMID- 2593821 TI - Rheotaxis of Biomphalaria glabrata on vertical substrates and its role in the recolonization of habitats treated with molluscicides. AB - The authors observed specimens of Biomphalaria glabrata climbing up the vertical wall of a ditch against the current. The snails that showed this behavior during application of a molluscicide in the breeding site survived and probably played a role in repopulation, which was observed three months later. These observations motivated field and laboratory investigations which led the authors to conclude that: a) this species is able to climb vertical surfaces both in field and laboratory situations; b) the current of water, as a physical stimulus, is sufficient to trigger this behavior (rheotaxis); c) rheotaxis on vertical surfaces depends on the presence of a necessarily moderate current; d) there are indications that B. glabrata may undergo habituation with respect to rheotaxis on vertical walls; e) the relationship between rheotaxis and habituation should be considered as a factor causing snail grouping in water bodies which may contribute to their localization in the field; f) rheotaxis on vertical surfaces may facilitate population dispersal, and its occurrence should be considered when campaigns for the control of schistosomiasis transmission are planned. The authors present some proposals to avoid the manifestation of this behavior in some field situations. PMID- 2593822 TI - Colicinogeny in Salmonella serovars isolated in Brazil. AB - A study of colicinogeny was made in 748 strains of Salmonella (97 serovars) isolated from different sources: human (291), animal (119), environmental (141), food (102) and animal feed (95). Colicin production was detected in 64 strains (8.6%), particularly isolated from foods (30.4%). Col E1 (53) and Ia (44) were the most frequently observed, especially in S. agona for environment and food sources. Col V production was identified in 5 strains of S. typhimurium within 8 producer cultures isolated from humans. Its relationship with the sources and serovars of Salmonella are discussed. PMID- 2593823 TI - Virological study of a dengue type 1 epidemic at Rio de Janeiro. AB - A dengue outbreak started in March, 1986 in Rio de Janeiro and spread very rapidly to other parts of the country. The great majority of cases presented classical dengue fever but there was one fatal case, confirmed by virus isolation. Dengue type 1 strains were isolated from patients and vectors (Aedes aegypti) in the area by cultivation in A. albopictus C6/36 cell line. The cytopathic effect (CPE) was studied by electron microscopy. An IgM capture test (MAC-ELISA) was applied with clear and reproducible results for diagnosis and evaluation of virus circulation; IgM antibodies appeared soon after start of clinical disease, and persisted for about 90 days in most patients. The test was type-specific in about 50% of the patients but high levels of heterologous response for type 3 were observed. An overall isolation rate of 46.8% (813 virus strains out of 1734 specimens) was recorded. The IgM test increased the number of confirmed cases to 58.2% (1479 out of 2451 suspected cases). The importance of laboratory diagnosis in all regions where the vectors are present is emphasized. PMID- 2593825 TI - Cerdocyon thous (L.) (Carnivora, Canidae) naturally infected with Leishmania donovani chagasi (Cunha & Chagas, 1973) in Corumba (Mato Grosso do Sul State, Brazil). PMID- 2593824 TI - [Strategy of Ascaris lumbricoides and Trichuris trichiura for the environmental contamination, in an endemic area]. AB - The distribution of frequencies of the number per grame of Ascaris lumbricoides and Trichuris trichiura in the faeces of naturally infected human in endemic areas, were found following a negative binomial distribution and an overdispersal pattern, independently of the ages of hosts. These results show, that only few hosts, independently of their ages, are involved in the higher environment contamination. PMID- 2593826 TI - Control of mycoplasma contamination in hybridoma technology. PMID- 2593827 TI - Correlation of plasma lipid fractions with colorimetrically determined glycated hemoglobin in a nondiabetic population. AB - To evaluate the incidence of protein glycation (measured as glycated hemoglobin) on plasma lipid levels in a free-living population, a colorimetric method has been used to detect 5-hydroxymethylforfural (HMF) released from glycated hemoglobin (GHb) and enzymatic methods have been used to evaluate total cholesterol, high-density lipoprotein (HDL) cholesterol, fasting glycemia, and total plasma triacylglycerides. These results have been used to calculate low density lipoprotein-(LDL) cholesterol levels with the Friedewald formula. Results show that a positive correlation exists in men, but not in premenopausal women, between GHb and fasting glycemia (P less than 10(-14], GHb and total plasma cholesterol (P less than .001), GHb and LDL cholesterol (P less than .0001), and GHb with the atherogenic index total/HDL cholesterol (P less than .0001), whereas a negative correlation was shown between GHb and HDL cholesterol (P less than .05). Fasting glycemia does not correlate with cholesterol lipoprotein fractions, but correlates well with total triacylglycerides. These correlations are significant when they are adjusted by age and body mass index. It has also been observed that the positive correlation between glycation of hemoglobin and total cholesterol occurs constantly at all glycohemoglobin levels, and affects all cholesterol fractions analyzed. This suggests an increased atherogenicity with increasing glycohemoglobin levels. Comparisons between groups with high and low GHb levels show variations in the order of 6.5% of total cholesterol levels and a major proportion in the different cholesterol fractions. The higher-range "glycated" populations show total cholesterol, LDL cholesterol and HDL cholesterol values significantly different from the lower-range "glycated" population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593828 TI - Phenolic and tyrosyl ring iodothyronine deiodination by the Caco-2 human colon carcinoma cell line. AB - Thyroid hormone metabolism was studied in the human Caco-2 colon carcinoma cell line, which at confluence exhibits several functions of differentiated enterocytes. Cells were harvested two to 17 days after reaching confluence. Intact cells and homogenates were tested for deiodination of [125I]-labeled substrates. Small amounts of thyroxine (T4) were converted by homogenates to 3,3',5'-triiodothyronine (rT3), 3,3'-diiodothyronine (3,3'-T2), and 1-, with no detectable production of 3,5,3'-triiodothyronine (T3) by homogenates or cells. rT3 was converted to 3,3'-T2 and 1- with an apparent Michaelis constant (Km) for rT3 of 24 nmol/L; 6-n-propyl-2-thiouracil (PTU) had a 50% inhibitory concentration of 30 nmol/L and abolished rT3 5'-deiodination at 1 mmol/L in the presence of 20 mmol/L dithiothreitol (DTT). T3 was deiodinated to 3,3'-T2 and 3' monoiodothyronine (3'-T1) with an apparent Michaelis constant (Km) for T3 of 5.7 nmol/L; this reaction was not inhibited by 1 mmol/L PTU. Phenolic and tyrosyl ring deiodinating activities were maximal four and six days, respectively, after the cells reached confluence. Homogenates of cells grown in standard medium containing fetal calf serum had fivefold higher rT3 5'-deiodinating activity than cells grown in a serum-free defined culture medium, reflecting a fivefold difference in the apparent Vmax with no difference in the apparent Km for rT3. There was no difference in T3 5-deiodination rates in homogenates of Caco-2 cells grown in the two media until 12 days postconfluence, when cells grown in standard medium had higher activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593829 TI - Hyperglycemia may determine fibrinopeptide A plasma level increase in humans. AB - The effects of hyperglycemia on plasma fibrinopeptide A (FPA) levels in normal subjects are reported. An increase of FPA concentration parallel to sustained hyperglycemia was observed; when the glycemia returned to basal values, FPA showed values in normal range. Heparin infusion was able to significantly decrease the hyperglycemia-induced augment of FPA levels. Isovolumic-isotonic NaCl solution infusion produced a slight (NS) increase in FPA levels; however, mild hyperglycemia, achieved by glucagon, was also able to produce a significant increase in FPA concentration. These data demonstrate the direct role of hyperglycemia in conditioning FPA level, and suggest that hyperglycemia, by itself, is a sufficient stimulus to produce thrombin activation in humans. PMID- 2593830 TI - Effects of phospholipid or cholesterol enrichment of rat intestinal brush border membrane on membrane order and transport of calcium. AB - Calcium uptake by brush border membrane vesicles from rat small intestine measured under initial rate conditions comprises both saturable and nonsaturable components. Because the brush border is a lipid bilayer and may be sensitive to changes in membrane lipid, vesicles were treated with liposomes to enrich phospholipid (PL) or cholesterol (C) content above that of the control (Reference) vesicle. The effects of the changes in lipid composition on membrane fluidity were determined from fluorescence anisotropy (r) of diphenylhexatriene. Compared with Reference vesicles, liposome-treated vesicles showed decreased Vmax for saturable and KD for nonsaturable uptakes. Liposome treatment changed vesicle phospholipid composition compared with Reference vesicles. Liposome-treated vesicles had similar phospholipid composition but differed in greater cholesterol content of C- compared with PL-vesicles. Mean Vmax and KD were lower in C- than PL-vesicles, but the difference did not reach statistical significance, although fluidity was significantly lower in C- than PL-vesicles. The mechanism of inhibition of saturable calcium uptake in PL- and C-vesicles was uncompetitive. Thus, lipid composition is crucial for determining calcium uptake: any change from native lipid composition decreased transport. Fluidity, measured by the conventional probe diphenylhexatriene, did not correlate with calcium uptake by Reference compared with liposome-treated vesicles. PMID- 2593831 TI - Serum apolipoprotein E in children and adolescents: the Bogalusa Heart Study. AB - Serum apolipoprotein (apo) E levels and its relationship to lipids and lipoprotein cholesterol fractions were examined in a random subsample (n = 561) of children and adolescents (7 to 17 years of age) from a total biracial community. Mean (+/- SD) levels of apo E were higher in blacks (males 4.8 +/- 1.8 mg/dL; females 5.2 +/- 1.8 mg/dL) than in whites (males 3.9 +/- 1.2 mg/dL; females 4.3 +/- 1.0 mg/dL) irrespective of sex (P less than .001). The black white difference in apo E persisted after controlling for the covariates: sexual maturation, age, adiposity, cigarette smoking, alcohol use, and oral contraceptive use (P less than .001). A sex differential (females greater than males, P less than .01) for apo E was seen in both racial groups. Apo E levels were inversely associated with age (P less than .01) and sexual maturation (P less than .05) only in white males. Apo E related positively and significantly to total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol fractions (HDL2-C and HDL3-C) in certain race-sex groups. Race, HDL2-C, triglycerides (very-low density lipoprotein cholesterol), HDL3-C, and sex were identified as predictor variables for apo E, in that order, and accounted for 21% of its variability in serum. It is conceivable that the observed race-sex differences in apo E may be related to apo E-HDL subfraction, which is thought to participate in the reverse cholesterol transport. PMID- 2593832 TI - Protein and amino acid metabolism during early starvation as reflected by excretion of urea and methylhistidines. AB - Endogenous excretion of nitrogenous products was studied during early starvation in six healthy, nonobese subjects after six days on a well-defined diet, designed to achieve net protein balance and an adequate calorie supply. The diet contained 0.5 g myofibrillar-free protein and 35 kcal/kg body weight. The subjects then fasted for three days. Urine was collected for 24-hour periods and analyzed for urea, ammonia, 3-methylhistidine, and 1-methylhistidine. Blood glucose and serum urea levels were measured daily. In a second group of subjects, muscle biopsies for determination of free amino acid concentrations were taken in the overnight fasted state and after three days of fasting. During the period with a balanced diet, urea production fell initially and stabilized after two to three days at a level of 146 +/- 15 mmol/24 h. During the period of fasting, serum urea increased from 3.0 +/- 0.4 to a maximum value of 6.2 +/- 0.7 mmol/L and urea production rose markedly, to a peak of 293 +/- 16 mmol/24 h. Ammonia excretion was 24 +/- 2 mmol/24 h before and 71 +/- 13 mmol/24 h after three days of fasting. 3 Methylhistidine excretion was stable before fasting and then rose from 154 +/- 17 to 198 +/- 17 mumol/24 h. 1-Methylhistidine excretion was unchanged during fasting. Blood glucose levels were stable at 4.8 +/- 0.2 mmol/L before fasting and then fell to 3.7 +/- 0.3 mmol/L. Intracellular concentrations of amino acids in skeletal muscle decreased markedly during fasting; after three days of fasting the glutamine concentration had fallen by 34%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593833 TI - Augmentation of protein degradation by L-triiodothyronine in uremia. AB - To ascertain if excessive protein catabolism is a feature of uremia, we determined leucine flux and nitrogen balance in 11 stable chronic dialysis patients and in 7 normal subjects. Leucine flux was determined during primed constant infusion of 2H3 and 15N leucine. Nitrogen balance was determined by measurement of nitrogen in the food, dialysate, and urine, and in the dialysis patients by correcting for the changing urea nitrogen pool. To assess if thyroid hormone adversely affects protein metabolism, the above-mentioned studies were done once in the basal state and once after a 7-day course of L-triiodothyronine (T3) treatment. Leucine carbon flux (mumol/kg/min) was 1.22 +/- 0.05 in the controls and 1.40 +/- 0.09 in the renal patients in the basal state (P = NS). Following T3 treatment, leucine carbon flux was increased to 1.40 +/- 0.05 and 1.72 +/- 0.09, respectively, in the controls and the renal patients (P less than .05). Fractional increment of the leucine carbon flux was 14% +/- 3% in the controls and 23% +/- 9% in the renal patients (P less than .05). The leucine nitrogen flux (mumol/kg/min) was 2.10 +/- 0.15 in the controls and 2.54 +/- 0.23 in the renal patients in the basal state (P = NS), and increased to 2.48 +/- 0.14 and 3.44 +/- 0.22, respectively, in controls and renal patients after T3 administration (P less than .05). Fractional increment of leucine nitrogen flux was 19.5% +/- 4.3% in the controls and 36.4% +/- 5.0% in the renal patients (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593834 TI - Resting energy expenditure in Gaucher's disease type 1: effect of Gaucher's cell burden on energy requirements. AB - The resting energy expenditure (REE; kcal/d) of 25 patients with Gaucher's disease type 1 was determined by indirect calorimetry. The average observed REE for the group was approximately 44% greater (P less than .01) than that predicted (predicted REE) for these patient's age, sex, height, and weight. The increased caloric requirements of these patients was manifested by a height-for-age less than or equal to the fifth percentile in seven of nine growing children and a muscle mass of less than the fifth percentile in 15 of 19 patients studied. The excess REE (observed REE--predicted REE) for individual Gaucher's disease type 1 patients was directly related to their liver volume as estimated from radionuclide scans and to the mass of the spleen as measured at splenectomy. The relationship between spleen mass and excess REE was demonstrated by an average 22.0% decrease in REE following splenectomy in five patients. Based on these data, the metabolic rate of the splenic tissue removed from the patients was calculated to be 96.8 kcal/d/kg, about twofold to threefold less than that of normal splenic tissue. These findings indicate that the elevated REE observed in these patients resulted from the large mass of Gaucher's cells, which although individually hypometabolic, were cumulatively an excessive metabolic burden. Furthermore, they suggest that indirect calorimetry may be a quantitative tool for measuring disease progression and the effect of therapeutic intervention in Gaucher's disease type 1. PMID- 2593835 TI - Computed tomography-measured trunk fat and plasma lipoprotein levels in nonobese women. AB - The associations between total adiposity, adipose tissue distribution measured by computed axial tomography (CAT), regional variation in fat cell size, and plasma lipoprotein levels were studied in a sample of 22 premenopausal healthy nonobese women aged 34.6 +/- 3.1 years (mean +/- SD) (% body fat, 27.8 +/- 5.8). In these nonobese women, no associations were found between total adiposity, adipose tissue distribution, and plasma triglyceride or very-low-density lipoprotein levels. However, total adiposity (as reflected by the body density-derived fat mass and by the adipose tissue volume measured by CAT), as well as the total trunk fat areas (measured at the abdominal and thoracic levels) were positively correlated with plasma low-density lipoprotein (LDL) cholesterol (.05 greater than P less than .01) and LDL apolipoprotein (apo) B (.05 greater than P less than .0005) levels. Because of these associations with LDL-C and LDL apo B levels, these body fatness indicators were negatively correlated with the HDL cholesterol/LDL-cholesterol and HDL-apo A-I/LDL-apo B ratios. However, few significant associations were observed between the proportion of abdominal fat estimated by the waist/hip circumference ratio (WHR) and the lipoprotein-lipid profile (r = .45 and r = .44, P less than .05 with HDL triglyceride (TG) and LDL apo B/LDL-cholesterol ratio, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2593836 TI - Potential associations between resting energy expenditure, thermic effect of a meal, and VO2 max in young adult males. PMID- 2593837 TI - Biomembranes. Part R. Transport theory: cells and model membranes. PMID- 2593838 TI - Inhibition kinetics of carrier systems. PMID- 2593839 TI - Design of simple devices to measure solute fluxes and binding in monolayer cell cultures. PMID- 2593840 TI - Generation of steady-state rate equations for enzyme and carrier-transport mechanisms: a microcomputer program. PMID- 2593841 TI - Liposome preparation and size characterization. PMID- 2593842 TI - Preparation of microcapsules from human erythrocytes: use in transport experiments of glutathione and its S-conjugate. PMID- 2593843 TI - Kinetics of transport: analyzing, testing, and characterizing models using kinetic approaches. PMID- 2593844 TI - Spontaneous insertion of integral membrane proteins into preformed unilamellar vesicles. PMID- 2593845 TI - Gentle and fast transmembrane reconstitution of membrane proteins. PMID- 2593847 TI - Lipid coumarin dye as a probe of interfacial electrical potential in biomembranes. PMID- 2593846 TI - Measuring electrostatic potentials adjacent to membranes. PMID- 2593849 TI - Use of nonequilibrium thermodynamics in the analysis of transport: general flow force relationships and the linear domain. PMID- 2593848 TI - Modulation of membrane protein function by surface potential. PMID- 2593850 TI - Cell separation by gradient centrifugation methods. PMID- 2593851 TI - Cell separation by elutriation: major and minor cell types from complex tissues. PMID- 2593852 TI - Pancreatic acini as second messenger models in exocrine secretion. PMID- 2593853 TI - Ascites cell preparation: strains, caveats. PMID- 2593854 TI - Direct current electrical measurement in epithelia: steady-state and transient analysis. AB - A method has been presented for the determination of resistance of biological tissues in which the PD response to step currents is determined. The delta PD after the dielectric capacitors are charged, divided by the current, gives the resistance, provided the current density is low enough so that the tissue behaves as a linear-bilateral system. In the gastric mucosa the PD continues to increase after the dielectric capacitors are charged and it is shown that this part of the delta PD is due to polarization of EMFs and should not be used in determining the resistance. It has been shown that (1) resistance measurements have enabled us to demonstrate that during acid secretion there is a neutral mechanism(s) for the movement of HCO3- out of and the entrance of Cl- into the oxyntic cells, (2) the transmucosal resistance varies inversely with the rate of acid secretion, and (3) the low resistance of the secreting frog fundus is due to the low resistance of the lumen-tubular cell pathway--the parallel pathways (the TIC or paracellular and surface cell pathways) have high resistances. The results of both the resistance and PD measurements have recently been analyzed with respect to the problem of whether the proton pump is neutral or electrogenic in the intact tissue. PMID- 2593855 TI - Impedance analysis in tight epithelia. PMID- 2593856 TI - Electrical impedance analysis of leaky epithelia: theory, techniques, and leak artifact problems. PMID- 2593857 TI - Ionic permeation mechanisms in epithelia: biionic potentials, dilution potentials, conductances, and streaming potentials. PMID- 2593858 TI - Cultures as epithelial models: porous-bottom culture dishes for studying transport and differentiation. PMID- 2593859 TI - Volume regulation in epithelia: experimental approaches. PMID- 2593860 TI - Scanning electrode localization of transport pathways in epithelial tissues. PMID- 2593861 TI - Experimental control of intracellular environment. PMID- 2593862 TI - Resonance energy transfer microscopy: visual colocalization of fluorescent lipid probes in liposomes. PMID- 2593863 TI - Effects of ovariectomy on blood and plasma viscosity, fibrinogen and whole blood filterability. AB - Blood and plasma viscosity, fibrinogen concentrations and whole blood filterability (VB) were evaluated before surgery and 7 and 30 days postoperatively in 2 groups of subjects, one of which comprised 10 hysterectomized women and the other 14 women who had undergone both hysterectomy and ovariectomy. Oestrogens and various metabolic haematological parameters were measured and correlated with the haemorrheological data. By day 7 after surgery fibrinogen concentrations and plasma viscosity had increased, while VB had decreased. Plasma viscosity and fibrinogen levels correlated negatively with VB in the non-ovariectomized women. Three weeks later almost complete normalization of all parameters was observed in all of the subjects, except for the persistence of low oestrogen concentrations and a further decrease in VB values in the ovariectomized patients, these parameters showing a positive correlation. This study demonstrates that haemorrheological alterations occur after hysterectomy (with or without ovariectomy) in the early post-operative period. The striking decrease in VB values and its correlation with the oestrogen concentrations observed 1 mth after ovariectomy suggest that the fall in oestrogen levels might be responsible for the decrease in whole blood filterability. PMID- 2593864 TI - A novel statistical approach to analysis of bleeding patterns during continuous hormone replacement therapy. AB - Previous studies have shown that continuous oral oestrogen-progestogen therapy, which is a relatively new treatment regimen, does not induce endometrial hyperstimulation. However, bleeding disturbances are common during the early months of therapy and in the present study we used both conventional methods of statistical analysis and a stochastic model to describe the bleeding patterns. Four groups of 15 post-menopausal women were given different oral formulations continuously for 1 yr. The oestrogen component in all cases was 2 mg 17 beta estradiol. The progestogen used was norethisterone acetate at a dose of either 1 mg or 0.5 mg (Groups A and B) or megestrol acetate at a dose of either 5 mg and 2.5 mg (Groups C and D). Each woman kept a daily record of all bleeding episodes, 80% of which occurred during the first 4 mth of therapy. Analysis of variance showed that the high doses of the two progestogens were associated with less spotting and menstrual-like bleeding than the low doses. Stochastic analysis of the bleeding data confirmed that women on the high progestogen doses experienced fewer bleeding episodes than those on the low doses. It also showed that women receiving the high progestogen doses who weighed under 67 kg or had had their last menstruation over 5 yr previously bled less than the other women in the high dose groups. PMID- 2593866 TI - Short-term effects of topical 17 beta-oestradiol on human post-menopausal skin. AB - Early studies performed between 1946 and 1952 reported that cutaneously applied oestrogens had local effects in spite of probable systemic absorption. In order to test the validity of these observations the epidermal effects of topically applied 17 beta-oestradiol (E2) of 8 post-menopausal women were studied in a double-blind placebo-controlled cross-over study using non-invasive bioengineering techniques. E2 or placebo was applied twice daily for 45-50 days in a gel (at concentrations of 0.1 mg/g and 1.0 mg/g) and the results were compared. Changes in epidermal hydration (electrical capacitance and conductance) and mechanical properties were studied. We were unable to confirm the short-term local oestrogenic effects on post-menopausal human skin reported in the earlier studies. Thus, in spite of its high number of oestrogen receptors, the epidermis does not appear to be a target organ for oestrogens under clinical conditions. PMID- 2593865 TI - Vaginal administration of low-dose oestradiol--effects on the endometrium and vaginal cytology. AB - Twenty (20) post-menopausal women, mean age 62.4 yr, presenting with symptoms associated with urogenital atrophy were treated intravaginally with daily doses of 25 and 50 micrograms oestradiol (E2) in a double-blind, cross-over study. After randomization, the patients started daily treatment with pessaries containing either 25 or 50 micrograms E2 for 3 wk, followed by a maintenance period of 6 wk during which the pessaries were used only twice a week. A 4-wk wash-out period was followed by another treatment period of 9 wk. The effects on the karyopyknotic index (KPI) and on endometrial histopathology were assessed before and after 3, 9, 16 and 22 wk of treatment. In the case of the 25 micrograms dose the mean KPI values were 34.7 and 20.9% after 3 and 9 weeks of treatment, respectively, the corresponding figures after treatment with 50 micrograms E2 being 39.2 and 22.7%. No dose-effect relationship was apparent from the vaginal cytology findings. Endometrial biopsies could not be taken systematically in all patients. Weak proliferation of the endometrium was observed in 1 woman after 3 wk of daily treatment with the 50 micrograms dose. No endometrial stimulation was detected in any of the patients after treatment with 25 micrograms daily. Beneficial clinical and cytological effects were obtained with both dosage regimens. Daily intravaginal administration of 25 micrograms E2 can accordingly be advocated for the treatment of urogenital symptoms attributable to oestrogen deficiency in post-menopausal women. PMID- 2593867 TI - Action of mycosubtilin on erythrocytes and artificial membranes. AB - Mycosubtilin has a strong lytic action upon erythrocytes. The haemolytic effect of the antibiotic is inhibited by free cholesterol as well as cholesterol included in liposomes of phosphatidylcholine-cholesterol. The antibiotic binding on artificial membranes was studied with radioactive bilayer vesicles of dipalmitoylphosphatidylcholine (DPPC), and DPPC-cholesterol:mycosubtilin destroyed both kinds of vesicles. The inhibition of the haemolytic effect of mycosubtilin by liposomes is a result of an interaction which diminishes the concentration of free cholesterol. PMID- 2593868 TI - Cytotoxicity of certain organic solvents and organophosphorus insecticides to the ciliated protozoan Paramecium caudatum. AB - Responses of Paramecium caudatum, a ciliated protozoan, to acute exposures of certain organic solvents and organophosphorus insecticides (OPI) were studied by determining their lethal concentration (10 min-LC100) and median lethal concentration (4 h-LC50). The solvents and OPI evoked a distinct sequence of responses. Among the five solvents tested, acetone proved most toxic [LC-2.9% and LC50-0.68% (v/v)], while dimethyl sulphoxide (DMSO) showed least toxicity [LC 11.0% and LC50-3.16% (v/v)]. The order of toxicity of solvents was: acetone greater than ethanol greater than methanol greater than N, N-dimethylformamide greater than dimethylsulphoxide. The LC values of six OPI dissolved in either acetone or DMSO indicated that they were more toxic when dissolved in acetone and least toxic in DMSO. Among the OPI, bromophos proved most toxic (LC-10 ppm) while malathion showed least toxicity (LC-200 ppm) in DMSO. The order of toxicity of OPI was: bromophos greater than pirimiphos-methyl greater than parathion methyl greater than dichlorvos greater than fenitrothion greater than malathion. The 4 h LC50 values computed for bromophos and malathion (dissolved in DMSO) were 575 ppb and 19.9 ppm, respectively, indicating the high susceptibility of P. caudatum to bromophos. The results indicate that the Paramecium toxicity assay could be used as a complementary system to rapidly elucidate the cytotoxic potential of compounds. PMID- 2593869 TI - Aeromonas hydrophila strains with moderate virulence. AB - A group of Aeromonas hydrophila strains was obtained from very different origins which showed very similar characteristics (lipopolysaccharide, outer-membrane protein profile, toxin production, bacteriophage sensitivity and moderate virulence), besides the heterogenicity observed among the A. hydrophila strains. This group of A. hydrophila strains with moderate virulence can be easily recognized by their bacteriophage sensitivity pattern. PMID- 2593870 TI - Henry Ford one of six centers to study effects of AIDS on lungs. PMID- 2593871 TI - Financing today's medical practice. PMID- 2593872 TI - An insatiable desire for work makes Robert J. Sokol, MD one busy dean. PMID- 2593873 TI - Professional liability--the Swedish experience. PMID- 2593874 TI - Identification of species and capsular types of Klebsiella clinical isolates, with special reference to Klebsiella planticola. AB - In the 77 reference strains for Klebsiella K types, there are 17 strains (22.1%) of Klebsiella planticola, 6 strains (7.8%) of Klebsiella oxytoca, 1 strain (1.3%) of Klebsiella terrigena, and 53 strains (68.8%) of Klebsiella pneumoniae. The species K. planticola, which was originally isolated from botanical and aquatic environments and hence thus named, was also identified at high incidence (81 strains, 18.5%) among the 439 recent clinical isolates of Klebsiella species. Among these K. planticola strains of hospital origin, 52 (64%) were isolated from sputum, 17 (21%) from urine, and the remaining 12 (15%) from other sources. The capsular types of these isolates were determined by the gel precipitation reaction. Seventy of 81 K. planticola isolates (86.4%) were typable by antisera to Klebsiella reference strains for K types and the K types of the clinical isolates distributed to 35 kinds of K types. The proportion of typable strains among clinical isolates of K. planticola was very similar to those in K. pneumoniae (87.5%) and K. oxytoca (86.0%). PMID- 2593875 TI - Replication of measles virus in Vero cells at elevated temperatures. AB - In one-step growth experiment of measles virus (MV) in Vero cells at 39 C, the appearance of MV infectivity was delayed for 24 hr and the maximum titer was reduced by approximately 1,000-fold, when compared with those at 35 C. MV infectivity was thermolabile at the high temperature. Penetration was rather enhanced at 39 C. By Northern blot hybridization, viral RNAs including 50S genome sized RNA and mRNAs were first detectable 24 hr post-infection (PI) at 35 C and 36 hr PI at 39 C, respectively. Rapid degradation of viral mRNAs was not observed in the infected cells at 39 C. The synthesis of N, F, and M proteins was relatively reduced at the high temperature and appearance of the other viral protein was delayed, in agreement with the time course of viral RNA synthesis. All these data suggest that less efficient synthesis of viral RNA, restriction of synthesis of N, F, and M proteins at translational level and thermolability of infectivity are all involved in the suppressed MV production in Vero cells at 39 C. PMID- 2593876 TI - Studies on B-cell memory. IV. Effects of lipopolysaccharide on primary and secondary antibody responses to T-independent type-2 (TI-2) antigen in mice. AB - Effects of LPS on primary and secondary antibody responses to typical TI-2 antigens were investigated in mice. Simultaneous injection of LPS with a TI-2 antigen showed only little adjuvant effect on the following primary antibody response to the antigen. In contrast, either a single or multiple injections of LPS, prior to the immunization with a TI-2 antigen, significantly augmented the following primary antibody response to the antigen. LPS, however, inhibited the development of B-cell memory to a TI-2 antigen when administered together with the antigen. Moreover, an injection of LPS in mice, which had strong IgM and IgG B-cell memories to a TI-2 antigen, caused disappearance or profound reduction of the memories. The results suggest that LPS produced by gram-negative bacteria exerts inhibitory effects on the development and continuation of B-cell memory to bacterial infections. PMID- 2593877 TI - Suppressive effect of interferon-beta-activated natural killer cells on lipopolysaccharide-induced B cell differentiation of MRL/Mp-lpr/lpr mice. AB - The suppressive effects of mouse recombinant interferon-beta (IFN-beta) on B cell differentiation of MRL/Mp-lpr/lpr (MRL/1) mouse, a model of autoimmune diseases, and C3H/H2 mice, a normal situation, were investigated. Spleen mononuclear cells were cultured in the presence of lipopolysaccharide (LPS), and the suppressive effect of IFN-beta was examined on differentiation of B cells to plaque-forming cells (PFCs) by highly sensitive reversed hemolytic plaque assay. IFN-beta (5,000 10,000 units/ml) suppressed more than 50% of PFCs of both MRL/1 and C3H/H2 mice. This suppressive activity as well as the cytotoxicity of natural killer (NK) cells enhanced by IFN-beta was abrogated by treatment of the spleen cells with anti-asialo GM1 antibody in the presence of complement. This suppressive activity was also abrogated by intravenous administration of 20 microliter/mouse of anti asialo GM1 12 hr before cultivation of spleen cells. These results suggest that NK cells activated by IFN might be responsible for the immunoregulation in autoimmune diseases. PMID- 2593878 TI - Isolation of a Coxiella burnetii strain that has low virulence for mice from a patient with acute Q fever. AB - Coxiella burnetii was isolated from a patient with Q fever. It could not be determined whether this was an imported case or an indigenous one. Identification of the isolate was made by electron microscopic morphology and the indirect fluorescent antibody test with convalescent-phase serum from a Q fever patient having a known titer of antibody to C. burnetii. The isolated strain, named TK-1, caused no symptoms in ddY and BALB/c mice except when the mice were treated with cyclophosphamide. PMID- 2593879 TI - Psychological tests to measure the effects of medical education on students' interpersonal skills. AB - The consulting skills required of medical students and practitioners have been categorized into a number of specific skills, two of which are: students' ability to empathize with the patient; and ability to decode non-verbal cues given by the patient in the interview. Training programmes to improve students' consulting skills are usually evaluated using analysis of students' actual interview behaviours with patients. Broad psychological and personality tests have also been used to measure changes in students' interviewing skills, but have generally not been successful. The hypothesis is advanced that more specific tests of the skills of interviewing, such as non-verbal sensitivity and empathy, would detect changes in students' ability to display these skills. As part evaluation of a consulting skills training programme, clinical students completed psychological tests of empathy and non-verbal sensitivity. Subsequent comparisons between trained and control student groups revealed no clear pattern in test results. These data suggest that specific psychological tests of empathy and non-verbal sensitivity may be no more effective in detecting changes in students' interpersonal skills than global personality measures. PMID- 2593880 TI - Analysing qualitative data: ethnography and the evaluation of medical education. AB - Quantitative methods of evaluating the outcomes of medical education may not always deliver the information which course organizers and teachers most need in order to improve their courses. Qualitative methods of research could provide such information. However, the use of qualitative methods has been limited by the difficulties associated with the analysis of subjective data and by the validity of its results. Qualitative data from an evaluation of the 2-year part-time MSc Course in General Practice at Guy's and St Thomas's Hospitals are presented and a rigorous method of analysis demonstrated. It is argued that for qualitative research validity is progressively achieved through the process of analysis, unlike experimental research where validity is ascribed in the research design. The relationship of research methods and approaches to evaluation is discussed and the potential contribution of qualitative research methods is outlined. PMID- 2593881 TI - Teaching medicine in general practice: the Guy's experience. AB - The development of teaching in general practice at Guy's Hospital Medical School is described. Important features of the current programme (a new programme for the United Schools of Guy's and St Thomas' Hospitals will come into effect this year) are the emphasis on learning directly from patients and the active role and responsibility given to clinical students. Students welcome the opportunities to see patients first, to deal with undifferentiated problems, to work with one clinical teacher, to put to use knowledge and skills and to test themselves as clinicians. In these circumstances they gain confidence and display the human qualities required of doctors. An acceptable service to patients, the essential basis for effective clinical teaching, requires the general practitioner teachers devote more of their time to service than to clinical teaching. PMID- 2593882 TI - Effects of the vocational training of general practice consultation skills and medical performance. AB - The effects of the vocational training of general practitioners in the Netherlands on the consultation skills and medical performance of junior doctors were studied. Results obtained at a training institute providing systematic training in these skills (Nijmegen) were compared with those at an institute taking a problem-based learning approach (Groningen). Trainees (n = 63) audiotaped consultations and recorded their medical performance at the start and at completion of training. The skills were evaluated with the aid of validated criteria and medical 'protocols'. Data on 631 pre-training and 624 post-training consultations were compared. Changes in consultation skills and medical performance occurred at both institutes and proved more marked at the institute providing systematic training. Improved medical performance was found to be associated with improved consultation skills. Enhanced clinical knowledge was found to be related to improved medical performance and consultation skills. The most profound changes were found in junior doctors who had started at a lower level of consultation skills and medical performance. PMID- 2593883 TI - Computer education of undergraduate medical students: a 2-year experience. AB - Computer literacy will become a necessity for doctors in the near future, as computer applications for clinical medicine are gradually developed and successfully implemented in the medical environment. Two years ago we began an optional course on computer systems for first-year medical students, as part of the biostatistics course at the University of Lisbon. The results of this experience show that computer education should be well adapted to the needs of students, and educators must continuously evaluate the students' reaction and anticipate the need for sudden changes in the course structure, which are often necessary to capture students' attention. PMID- 2593884 TI - The pre-registration year 1983-1988. AB - The pre-registration year, a mandatory period of general clinical training in the United Kingdom, has been the subject of recent comment and criticism. The literature on the year is analysed, taking as a starting point and framework the 1983 review by the Association for the Study of Medical Education (ASME), and focusing on the 1987 Recommendations of the General Medical Council. It is concluded that the pre-registration programme has been improved, but that attention needs to be given to house officers' hours of duty, to career counselling for them and to training for teachers and supervisors. PMID- 2593885 TI - Implications of AIDS for teachers of medicine to dental students. AB - A plea is made for a significant input on AIDS to the dental undergraduate curriculum by medical teachers. The suspicion is that in some schools the teaching of medicine to dental students is not treated seriously. Figures are quoted depicting the worldwide spread of AIDS. The risk of dentists acquiring HIV in the health care setting is discussed. Mention is made of infection control in the dental environment. The objectives are given of a medical curriculum for dental students. Some of the oral manifestations of AIDS are named. Symptoms and signs (which a dentist should be able to recognize) are given for pulmonary, neurological, gastrointestinal or neoplastic complications that may be found in HIV infection. The role of the dentist is stressed in continuing surveillance of patients with HIV infection. PMID- 2593886 TI - Essentials of problem-based learning. PMID- 2593887 TI - Multiculturalism and medicine in Australia. PMID- 2593888 TI - Sexual function in chronic disease. PMID- 2593889 TI - Factors in sexual dysfunction in diabetic female volunteer subjects. AB - The aetiology and management of diabetic impotence is well-documented; the effects of diabetes on female sexuality are not so clear. In this study, 48 diabetic women were assessed clinically and answered detailed sexual questionnaires during a semistructured interview with a sexual counsellor. Twenty four of the women reported one-or-more sexual dysfunctions: decreased libido, slow arousal, inadequate lubrication, anorgasmia or dyspareunia. There was no significant relationship between the presence of dysfunction and recent glycaemic control, the duration of diabetes, the presence of clinical complications or of neuropathy alone, or the attitude to sexuality. The sexual dysfunction(s) were present at the onset of diabetes in the majority of those so affected (17 of 24 patients), or were attributed to other causes in the remainder. It is suggested that sexual dysfunction in diabetic women should be treated actively as in "normal" women, since diabetes is not the major aetiological factor. PMID- 2593890 TI - The effect of selective therapy on malignant obstructive jaundice. AB - To determine the impact and use of alternative treatment methods of draining malignant obstructive jaundice, a review of 41 patients who were managed by a surgical hepatobiliary service, in which non-surgical (endoscopic and radiological) treatment modalities were available equally, was performed. Of the 41 patients, 39 patients experienced 45 attempted treatments with ultimate success in 35 (90%) patients. The non-operative management of the high-risk patients did not result in a higher mortality at 9% and 25% for endoscopic and radiological management, respectively, than that of 15% which was achieved in the operative series. As a result of treatment selection, the non-operative groups survived for a shorter time (eight weeks) than did those who underwent operation (survival, 30 weeks). This shorter survival time resulted in a similar readmission rate for the non-operative and operative groups; patients did not survive long enough in the non-operative group to develop stent complications. Even if surgery is the chosen treatment modality, preoperative endoscopic retrograde cholangiopancreatography is recommended in planning that surgery. We conclude that in patients with malignant obstructive jaundice, surgical treatment has the advantage of fewer late complications, while non-surgical treatment has the advantage of less initial morbidity or mortality. If the aim is to optimize palliation not only in the short term, but also in the longer term, then the selection of patients for treatment on the basis of pretreatment imaging results, the operative risk and the predicted duration of survival, will result in operative and non-operative methods of treatment being used approximately equally. PMID- 2593891 TI - Reducing blood cholesterol levels in patients with peripheral vascular disease: dietitian or diet fact sheet? AB - A randomized trial was performed to test the hypothesis that, among patients with peripheral vascular disease, no difference is achieved in the magnitude of the reduction in blood cholesterol levels as a result of advice which is provided by a dietitian and that which is provided by a diet fact sheet. Fifty-nine patients were allocated at random either to a "dietitian" group (n = 31) or to a "diet fact sheet" group (n = 28). Dietary advice which was provided by a dietitian involved two personal interviews; the diet fact sheet was prepared by the NSW Department of Health. Twenty-two and 23 members of each group, respectively, returned for follow-up at three months. The mean cholesterol level fell by 8.5% among the "dietitian" group but only by 1.9% among the "diet fact sheet" group. The difference of 0.47 mmol/L in the total cholesterol level reduction between the two groups was statistically significant (P = 0.02; 95% confidence interval, 0.88 to -0.07 mmol/L). It appears that individual advice which is provided by a dietitian is more successful in leading to a reduction in blood cholesterol levels than is the administration of a diet fact sheet, even though this particular diet fact sheet appears to be excellent and is used widely. In view of the large numbers of patients and of persons in the population as a whole who would benefit from a reduction in blood cholesterol levels, and the expense of individual advice to be provided by a dietitian, explorations of cost-effective methods of providing dietary advice are needed. PMID- 2593892 TI - Medical education for a multicultural society. AB - Australian medical education has not kept pace with Australia's increasingly multicultural society. Feedback from ethnic community organizations suggests that medical students and specialist trainees in medicine are not learning how to understand, to interact with and to treat patients in culturally appropriate ways. The first part of this paper reviews the problem and considers some perspectives in transcultural medicine and clinically applied medical anthropology. The second part proposes some areas in which medical schools can take the initiative in developing interdisciplinary teaching programmes at undergraduate and graduate levels. These programmes should provide minimal standards to enable any medical graduate to practise with patients of any cultural background and, in addition, will encourage some students to pursue more specialized studies in transcultural medicine and medical anthropology. It is suggested that new developments should be integrated with appropriate university departments such as anthropology. PMID- 2593893 TI - The iris of the anarchist. PMID- 2593895 TI - A tragic case of snake bite. PMID- 2593894 TI - Sacroiliac joint infection by Salmonella heidelberg. PMID- 2593896 TI - Effects of organochlorine pesticides. PMID- 2593897 TI - "GOMER" go home. PMID- 2593898 TI - The isolation of Malassezia furfur from an episode of peritonitis. PMID- 2593899 TI - Effects of the 1989 heart week campaign. PMID- 2593900 TI - Triple primary lung cancer. PMID- 2593901 TI - Sewage pollution of marine waters: the risks of viral infection. PMID- 2593902 TI - A venomous Christmas tour. PMID- 2593903 TI - Freckles, moles, melanoma and the ozone layer: a tale of the relationship between humans and their environment. PMID- 2593904 TI - Maternal mortality. PMID- 2593905 TI - Predictions of future cases of asbestos-related disease among former miners and millers of crocidolite in Western Australia. AB - In a cohort of 6502 male and 410 female former workers from the crocidolite (blue asbestos) mining and milling works at Wittenoom, Western Australia, there were 94 cases of malignant mesothelioma (12 cases of peritoneal mesothelioma), 141 cases of lung cancer and 356 successful compensation claims for asbestosis to the end of 1986. After adjusting for measured covariate effects by means of proportional hazards regression analysis, smooth curves were fitted to the resulting "underlying" incidence rates for malignant mesothelioma, lung cancer and asbestosis, separately, and for mortality of any cause. By the use of these curves and individual risk estimates, predictions have been made of the future incidence of these diseases to the year 2020. With the assumption that all subjects who were not known to be dead or departed overseas still were alive at December 31, 1986, and excluding persons of more than 85 years of age, the number of new cases of mesothelioma is expected to rise to a peak of around 25 cases per year in 2010, with an expected total number of 692 cases of mesothelioma (95% confidence interval [CI], 394-990 cases) between 1987 and 2020. A total of 2898 deaths (95% CI, 2284-3511 deaths) of any cause is expected in the same period. New cases of lung cancer and asbestosis are expected to continue at roughly the current rates of eight and 17 cases per year, respectively, before declining after the year 2000, leading to totals of 183 cases (95% CI, 34-335 cases) and 482 cases (95% CI, 236-728 cases), respectively, being expected by the year 2020. Predictions that were based on the censoring of subjects at the date that they last were known to be alive resulted in slightly higher, but probably less accurate, estimates. PMID- 2593906 TI - Fatal and non-fatal stingray envenomation. AB - A fatality occurred in a previously healthy 12-year-old boy after a penetrating chest injury from a stingray barb. The injury occurred under freak circumstances. Death was a result of cardiac tamponade which was secondary to venom-induced, localized myocardial necrosis and spontaneous perforation, six days after the direct penetration of the right ventricle by the barb. Three other cases of less serious stingray envenomation are described which illustrate the significant localized morbidity that may occur without immediate wound exploration and toilet after adequate anaesthesia. We also report a study of a series of 100 minor stingray envenomations which, when treated, resulted in no morbidity. It is possible that local infiltration with 1% plain lignocaine may have a direct counteraction against stingray venom that remains in the wound area. Stingray venom has insidious, but powerful, localized tissue necrosing properties in humans. PMID- 2593907 TI - Thrombocytopenia after brown snake envenomation. AB - The marked coagulation disturbances in patients after severe envenomation by brown snakes (genus Pseudonaja) were examined with particular emphasis on the sequential platelet counts. The common finding (in almost half the studied patients) of a progressive depletion in platelet numbers leading to thrombocytopenia, which in one case was severe, suggests that thrombocytopenia should be considered as a possible complicating factor in the management of these patients. This trend was not a feature of the cases that involved bites by tiger snakes. The finding of this study in relation to envenomation by brown snakes is in contrast to the widely held opinion that thrombocytopenia is not an outcome of snake-bites in Australia. PMID- 2593908 TI - When is a maternal death a maternal death? A review of maternal deaths at the Mercy Maternity Hospital, Melbourne. AB - The limiting of the reporting of maternal deaths to those that are included in the criteria of the World Health Organization excludes deaths which yield useful information for further improvements in clinical performance. In this series of 22 maternal deaths, six deaths would have been excluded from reporting: one "direct" obstetric death of pre-eclampsia; one "indirect" death as a result of renal and cardiac failure; two deaths as a result of postnatal depression which led to suicide three and four months postpartum, respectively; and two deaths of cancers, where diagnostic delay may have been a result of the coexistent pregnancy. The importance of primary pulmonary hypertension, cardiomyopathy and psychiatric illness is emphasized. We endorse the recent recommendation of the International Federation of Gynaecology and Obstetrics (FIGO) that all maternal deaths that occur more than 42 days after the end of a pregnancy should be assessed for possible relationships with childbirth, and suggest that a time limit of one year would include all deaths that are worthy of scrutiny. PMID- 2593909 TI - Thin-membrane nephropathy--a common cause of glomerular haematuria. AB - Thin-membrane nephropathy recently has been described as a cause of glomerular haematuria. The prognosis of the condition is unclear but it generally is considered to be benign. In a series of 92 patients with glomerular haematuria, thin-membrane nephropathy was found to be a common cause, occurring in 26 (28%) patients. Sixteen patients were women. The mean age was 42 years. Four patients had a family history of renal disease or haematuria and no patient was deaf. Haematuria had been present from six days to 30 years. Loin pain occurred in 31% of patients. Hypertension was not a feature and mild renal impairment was present in one case only, while a further three cases showed proteinuria at a level of greater than 500 mg of protein per day. Glomerular basement membranes in patients with thin-membrane nephropathy gave a mean (+/- standard deviation) width of 319 + 37 nm which was significantly (P less than 0.002) less than the control value of 394 +/- 61 nm. On the basis of clinical features and serological parameters, thin-membrane nephropathy could not be separated from other renal causes of haematuria but required careful electronmicroscopic examination of renal biopsy material to establish the diagnosis. Limited follow-up has confirmed the good prognosis of the condition. PMID- 2593910 TI - Cough, dyspnoea and fever in a young woman. PMID- 2593911 TI - Thoracic society of Australia and New Zealand. Asthma management plan, 1989. PMID- 2593912 TI - Injuries from Coleoptera. AB - The effects of Coleoptera (beetles) on humans in the Australian region are surveyed. Ill-effects range from the immediate trauma of a bite, possibly with minor effects from the beetle's salivary secretions, to the effects of the vesicating beetles of the families Meloidae, Oedemeridae and Staphylinidae, and also the acute corneal erosion that is attributed to the small beetle Orthoperus sp. (family Corylophidae) in southeastern Australia. Reference also is made to other effects that are known as a result of beetle metabolites or structures, such as "carpet beetle dermatitis" from the irritating hairs of Anthrenus larvae (family Dermestidae), and inhalational asthma from beetles, notably the grain weevil Sitophilus, the causative agent of certain cases of grain-worker's asthma. Beetles as human intestinal inhabitants, and their role as intermediary hosts of metazoal diseases are discussed. PMID- 2593913 TI - Renal failure and death after multiple stings in Papua New Guinea. Ecology, prevention and management of attacks by vespid wasps. AB - Although most species of wasps are solitary and no hazard to humans, attacks by colonies of large social wasps of the family Vespidae, which commonly are known as hornets, can result in envenomation with severe toxicity. The effects of such envenomation on six persons from Papua New Guinea are described and discussed in the light of other published reports from Melanesia, Asia, Europe and America. Four deaths and at least four cases of acute renal failure occurred. Vespa affinis (L.), 1764 was responsible for at least two deaths and Vespa tropica (L.), 1764 for one death. The ecology of vespids in Asia and the Pacific is reviewed and guide-lines for the prevention of wasp attacks are outlined, including appropriate clothing, and the recognition, avoidance and selective destruction of nests. A description is helpful in the identification of the species of insect that was responsible for clinical cases. Management includes hospitalization for victims of multiple stings, with careful monitoring for early and late damage to kidneys, blood, liver and muscle. PMID- 2593914 TI - The origin of human species: what we have learned about human evolution in the 130 years since On the origin of species. PMID- 2593915 TI - Prolonged hepatic cholestasis after flucloxacillin therapy. AB - A severe prolonged illness that was characterized by deep jaundice and debilitating pruritus occurred in five patients after the use of flucloxacillin. The symptoms and signs of liver disease took at least two months to resolve; after four- to nine-months' follow-up, liver enzyme activities have remained abnormal in all patients. Examination of liver biopsy specimens showed severe cholestasis in all cases, with evidence of significant bile-duct injury in three cases. In one patient, in whom symptoms have persisted for nine months, examination of a liver biopsy specimen showed marked bile-duct depletion. All patients were seen during a four-month period and it is felt that flucloxacillin induced liver disease probably has been under-diagnosed and underreported. The use of flucloxacillin has been increasing rapidly and it is anticipated that more cases of flucloxacillin hepatotoxicity will occur in the future. PMID- 2593916 TI - Delayed diagnosis of red-back spider envenomation: a timely reminder. AB - A case of the delayed diagnosis of envenomation by the redback spider (Latrodectus mactans hasselti) is reported. The common and more unusual presentations then are discussed, together with treatment guide-lines, and comparison is made with the management of latrodectism in the United States as a result of envenomation by the black-widow spider. PMID- 2593917 TI - Efficacy of funnel-web spider antivenom in human envenomation by Hadronyche species. AB - We describe the envenomation of three patients by Hadronyche versuta, Hadronyche infensa and Hadronyche cerberea (which all are species of funnel-web spider) and the reversal of symptoms by funnel-web spider antivenom. The importance of continuing to administer antivenom until symptoms are reversed is emphasized; all three patients required further doses of antivenom to reverse the symptoms completely. None of the patients had received first aid. PMID- 2593918 TI - Can cancer be cured by meditation and "natural therapy"? A critical review of the book You can conquer cancer by Ian Gawler. AB - There is a widespread belief that cancer is caused, at least in part, by aberrant mental processes. A corollary of this belief is that cancer may be cured by the application of the mind. These ideas are fostered in Australia by a popular book You can conquer cancer by Ian Gawler, a veterinary surgeon who attributes, at least in part, the development and subsequent cure of his own cancer to such processes. Critical examination of these beliefs finds evidence in their support to be lacking. None the less, many patients with cancer in this country follow the book's advice, often on the basis that it "at least can do no harm". While some patients may be aided to come to terms with their disease and to lead more fulfilling lives by taking up meditation and the positive approach to living that is described in the book, it also contains recommendations about orthodox treatments, life-style and diet which, if adopted uncritically, could be quite detrimental. The potentially harmful effects of accepting such unproved ideas about cancer need to be known more widely. Furthermore, because his ideas are making such an impact on the day-to-day treatment of cancer in this country, Gawler owes it to the community to justify, with evidence, his claims that by meditation patients with cancer may be enabled to achieve a cure of their disease in a way that is unattainable with orthodox medical treatment alone. PMID- 2593919 TI - The magnificent septimus. PMID- 2593920 TI - Carbon monoxide unlikely to be a hazard to bushfire fighters. PMID- 2593921 TI - The utilization of antenatal diagnosis by women of advanced maternal age in the New England Health Region, New South Wales. PMID- 2593922 TI - Diabetes in Papua New Guinea. PMID- 2593923 TI - The right to operate. PMID- 2593924 TI - The Disability Services and Guardianship Act 1987. PMID- 2593925 TI - Chlamydial prevalence: an increase? PMID- 2593926 TI - "Birthday card" reminders to increase measles immunization rates. PMID- 2593927 TI - "Hair-foot". PMID- 2593928 TI - Married men may eat healthier diets. PMID- 2593929 TI - Urban envenomation. PMID- 2593930 TI - Endoscopy compared with barium meal. PMID- 2593931 TI - Acute encephalopathy caused by human immunodeficiency virus apparently responsive to zidovudine. PMID- 2593932 TI - Conception, genetics and birth marks in aborigines. PMID- 2593933 TI - Urokinase in thrombotic coronary occlusion. PMID- 2593934 TI - Subcutaneous hydration. PMID- 2593935 TI - Chloramphenicol and bacterial meningitis: time for change. PMID- 2593936 TI - "Safe" obstetric outcomes in haemophiliac patients infected with the human immunodeficiency virus. PMID- 2593937 TI - Canned ashes. PMID- 2593938 TI - No 'flu this winter? PMID- 2593939 TI - Changing behaviour to prevent the spread of the human immunodeficiency virus. PMID- 2593940 TI - Sexual practices and "beats": AIDS-related sexual practices in a sample of homosexual and bisexual men in the western area of Sydney. AB - One hundred and seventy-six men who had engaged in sexual activity with other men in the past six months were interviewed, in the western area of Sydney, about their sexual activities and knowledge as related to the acquired immunodeficiency syndrome (AIDS). Comparisons were made between men who had frequented "beats" (public toilets, parks or isolated roads where men meet for homosexual encounters) in the past six months, and those who did not use beats. One-quarter of those men who frequented beats reported beats as their only venue for meeting men for sexual contact, while other men reported them as one of many venues that they used to meet men. Although all interviewed men were engaging in sexual activities with men, 12 men described themselves as heterosexual, and 12% of those men who used beats, and 7% of the beat non-users, were married or in de facto relationships. In comparing those who used beats with the beat non-users, 64% of beat users had engaged in sexual practices with between six and 50 different partners in the past six months compared with 8% of beat non-users. Beat users also were more likely to engage in unprotected anal intercourse with causal partners. Nineteen men claimed to be HIV-seropositive for the human immunodeficiency virus, with 11 of these men still engaging in high-risk sexual activities. The implications for AIDS education are discussed. PMID- 2593941 TI - A potential source for the transmission of the human immunodeficiency virus into the heterosexual population: bisexual men who frequent "beats". AB - Fifty-four actively bisexual men with recent sexual experiences with both men and women were interviewed as part of a wider study of 176 homosexual men, many of whom frequented "beats" (public toilets, parks and isolated roads where men meet for homosexual encounters). Forty-six per cent of the bisexual men were engaging in unsafe sexual practices with at least one man and one woman. Three of these men knew that they were seropositive for the human immunodeficiency virus, with two of these men engaging in unsafe sexual practices with some of their partners. Fewer than one-quarter of the bisexual men identified with or participated actively in aspects of organized, overt "gay" culture. So-called "closeted" bisexual men are suggested to be a major, but neglected, target for educational efforts against the acquired immunodeficiency syndrome. PMID- 2593942 TI - Sexual practices and condom usage in a cohort of homosexual men in relation to human immunodeficiency virus status. AB - Between January 1, and October 31, 1987, 420 homosexual men who participated in a cohort study of infection with the human immunodeficiency virus (HIV) completed a questionnaire that examined their sexual practices during the previous six months. Of the subjects, 205 (48.8%) men were HIV-seropositive and 215 (51.2%) men were HIV-seronegative. Although there was an appreciable level of condom usage in both groups, 13.5% of the HIV-seronegative men had engaged in unprotected receptive anal intercourse and 6.3% of the HIV-seropositive men had engaged in unprotected insertive anal intercourse. Condom breakage was reported on approximately 6% of occasions by a minority of subjects. Among subjects who were in a relationship with a regular male sexual partner, the most commonly reported sexual practices were deep kissing, mutual masturbation and receptive oral intercourse without ejaculation. No HIV-seronegative man engaged in unprotected receptive and/or insertive anal intercourse, receptive oral intercourse with ejaculation or receptive and/or insertive "fisting" with a regular partner who was HIV-seropositive. No HIV-seropositive man engaged in unprotected insertive anal intercourse to ejaculation with an HIV-seronegative partner, although they did so with partners who were HIV-seropositive or of unknown status. On multivariate analyses the subject's antibody status was found to be associated with receptive anal intercourse with a condom (P = 0.007) and mutual masturbation (P = 0.001), with HIV-seronegative men being more likely to practise either; no significant independent effect was associated with the partner's antibody status. These findings provide important information on the types and levels of sexual practices in a group of homosexual men after the recognition of the acquired immunodeficiency syndrome in this country. PMID- 2593943 TI - A prospective clinical audit of methadone maintenance therapy at the Royal Newcastle Hospital. AB - In a prospective study of 63 admissions to a methadone maintenance programme in a public hospital, 13 admissions were for less than two weeks. Of the remaining 50 such admissions, 35 admissions were terminated because of absenteeism, drug abuse, violence or drug-dealing. Twelve patients did not take intravenously administered drugs during the time that they were receiving methadone, but in 25 of the 50 admissions that lasted for more than two weeks, such drugs were abused at least fortnightly. Eight patients achieved a stable state without drugs that lasted at least three months. No improvements were note in patients' social situations, relationships, health or criminal activity, but compliant patients did improve their employment status. A significant minority of patients has benefited from methadone maintenance therapy, but most patients have continued their drug abuse and drug-related life-styles. PMID- 2593944 TI - Congenital syphilis is with us still. AB - A baby with neonatal congenital syphilis who was born prematurely at 33-weeks' gestation with hepatosplenomegaly, ascites and respiratory distress that was evident at birth is presented. PMID- 2593945 TI - The grass is not necessarily Eire on the other side. PMID- 2593946 TI - Corrigendum: a reappraisal of co-trimoxazole. PMID- 2593947 TI - The boring story of Agent Orange already is outdated. PMID- 2593948 TI - Traffic accidents are a political issue. PMID- 2593949 TI - "Repetition strain injury" in Telecom Australia. PMID- 2593950 TI - Communication of notifiable diseases. PMID- 2593951 TI - The availability of heroin. PMID- 2593952 TI - Reading ability and the use of condoms. PMID- 2593953 TI - A fresh look at the transmission of the human immunodeficiency virus. PMID- 2593954 TI - Treatment of prodromal shingles. PMID- 2593955 TI - Campylobacter pylori infection: diagnosis and therapy. PMID- 2593956 TI - Diabetes data--into the nineties. PMID- 2593957 TI - Computerized electrocardiographic interpretation: an analysis of clinical utility in 5110 electrocardiograms. AB - This study describes the initial experience with a computerized electrocardiographic interpretation system in a teaching hospital. The sensitivity and specificity of the 13,375 diagnostic statements that were used to describe the first 5110 electrocardiograms were analysed to determine the predictive accuracy of computerized electrocardiographic interpretation. Reviewing cardiologists inserted 1320 statements, deleted 1792 statements and modified 484 computerized statements. The over-all sensitivity and specificity (and standard error [SE]) of computerized diagnosis was 90.1% +/- 0.3% and 89.6% +/- 0.2%, respectively, with an over-all positive predictive accuracy (+/- SE) of 87.1% +/- 0.3% and a negative predictive accuracy (+/- SE) of 92.2% +/- 0.2%. Sensitivity and specificity were lowest for the category of ST-T wave changes (83.1% +/- 0.8% and 84.1% +/- 0.7%, respectively) and were highest for the category of sinus rhythm (96.6% +/- 0.3% and 97.0% +/- 0.6%, respectively). The positive predictive accuracy of computerized diagnosis was lowest for the category of hypertrophies (74.2% +/- 1.0%) and was highest for the category of sinus rhythm (99.5% +/- 0.1%), while for the category of myocardial infarctions it was 87.6% +/- 0.8%. The negative predictive accuracy ranged from 96.7% +/- 0.3% for the category of hypertrophies to 81.8% +/- 1.3% for the category of sinus rhythm. We conclude that the computerized analysis of electrocardiograms has a satisfactory predictive accuracy when used in an environment with a high prevalence of abnormalities. Electrocardiograms that are classified as normal by computerized analysis may not require checking; however, all electrocardiograms with abnormalities should be interpreted by a competent electrocardiographer. PMID- 2593958 TI - The 14C-urea breath-test for the detection of gastric Campylobacter pylori infection. AB - A breath-test has been developed for the detection of gastric infection with Campylobacter pylori. Urea that is labelled with carbon 14 is administered to a fasting patient and the patient's breath is sampled for radioactivity over the following 30 minutes. If C. pylori is present in the patient's stomach, urease activity causes hydrolysis of the urea and the 14C is absorbed as carbon dioxide. This carbon dioxide enters the patient's bicarbonate pool and eventually is excreted in the breath. The results are expressed as a percentage of the administered dose/mmol carbon dioxide x kg body weight. Sixty-three patients who were undergoing endoscopy were studied. The radioactivity in exhaled breath which was sampled within five minutes of 14C-urea administration was attributed to the presence of urease enzyme in mouth organisms and was discounted. The time radioactivity curves for breath samples from five to 30 minutes after the administration of 14C-urea gave an excellent separation between subjects with negative results of the examination of gastric-biopsy samples and patients with microbiological and histological evidence of infection with C. pylori. The area under the time-radioactivity curve at between five and 30 minutes after the administration of 14C-urea in 24 patients with negative microbiological results was 6.9 +/- 4.4 area units; in 35 of 39 patients with positive microbiological results, this area was greater than 40 area units. Measured against the results of the microbiological examination of gastric-biopsy samples, the sensitivity of breath-testing was 90% and the specificity was 100%. Measured against the results of histological examination for the presence of C. pylori infection, breath testing had a sensitivity of 94% and a specificity of 93%. A positive breath-test result also correlated well (P = 0.0001) with the serological antibody test result. The role of non-invasive tests--enzyme-linked immunosorbent assays and 14C-urea breath-testing--in the management of gastritis and peptic ulcer disease is discussed. We consider that the 14C-urea breath-test has an important role in the noninvasive confirmation of gastric infection with C. pylori and in the follow-up of patients after treatment. PMID- 2593960 TI - A slow weekend in Beverly Hills. PMID- 2593961 TI - Potential for leptospirosis among urban dwellers. PMID- 2593959 TI - The New Zealand Report of the cervical cancer inquiry: significance for medical education. AB - The New Zealand Cervical Cancer Inquiry has elicited considerable interest in Australia as well as in New Zealand. However, relatively little attention has been paid to the future practice of medicine with regard to the relevance of the Inquiry's findings for medical education, although it did recommend the incorporation of ethics teaching into all stages of the medical curriculum, and also urged that attention be paid to communication skills within the curriculum. In this article, I argue that medical ethics teaching should be seen as an essential part of the medical curriculum, with the teaching being integrated closely with the other disciplines that comprise the medical course. To illustrate one possible approach, I have outlined elements of current ethics teaching at the University of Otago. I also have raised what I regard as wider issues for the medical curriculum. These include the need for students to develop a critical facility and an ability to handle conflicting data and attitudes (fostered principally by an understanding of research methods), to appreciate the importance of accountability (fostered in part through group learning activities) and to be aware of the impact of community concerns on the practice of medicine. Another issue which I consider is raised indirectly by the Inquiry concerns the procedures that are used for the selection of students into medical courses. PMID- 2593962 TI - "Awareness" of hepatitis B infection among child day-care staff members. PMID- 2593964 TI - Utilization of "Smokescreen" smoking-cessation programme. PMID- 2593963 TI - Measles campaign: $11 million saved in New South Wales. PMID- 2593965 TI - [Safety forms for industrial lubricating oils: a working proposal at the national level]. AB - The health and safety data sheets for lubricating oils currently in use present considerable differences regarding the information they provide. Often, the information is either too generalized or incomplete--particularly on the chemical aspects of oils--and therefore the sheets are inadequate for the prevention and control of the occupational risks. For the purposes of harmonization, a data sheet has been prepared which takes into account the specific features of the products, and particularly the handling of confidential data. The most important oil manufacturers have been consulted, and they have agreed to use the data sheet in order to provide information on their products to the local health authorities. The widespread use of this data sheet should enable an easier comparison of the health and safety data of oils to be made, provide a better understanding of the information received and, consequently, evaluate the risks involved. PMID- 2593966 TI - Behaviour of biological indicators of internal dose and some neuro-endocrine tests in aluminium workers. AB - The authors present the results of toxicological studies on aluminium from 1983 to 1988. In order to obtain reference values for serum and urine aluminium, 506 healthy adults, not occupationally exposed to the metal, residing in the Brescia area were studied. The following values were obtained: AlS = 5.8 +/- 2.9 micrograms/l; AlU 11.9 +/- 4.3 micrograms/l. The AlU and AlS values did not differ in relation to age, sex, alcohol consumption, smoking habits and residence, contrary to what has been found for some metals determined in the urine and/or blood of the same subjects. In a group of 227 subjects with occupational exposure to aluminium within the range 0.1-1.0 mg/m3, the mean levels of AlU were higher than that of the reference population; however the AlU of the workers were generally lower than 20 micrograms/l which is the upper limit for the reference population; 4 workers who were under treatment with antiacid preparations showed AlU values higher than 150 micrograms/l. Seven workers exposed to atmospheric aluminium concentrations around the TLV-TWA had higher AlU values at the end of their shift on all working days and on Friday morning the values where higher than those encountered on Monday morning. On the other hand no daily and weekly fluctuations were evident for AlS. For 14 workers the relationship between AlU and AlS values were examined in three subsequent periods after the start of working activity. Considering the same values of AlU, it was observed that the AlS increased with the duration of exposure. These results seem to indicate that AlU could be considered as indicator of current exposure and AlS as an indicator of cumulative exposure. Neuroendocrine tests were performed every 6 months in 21 workers after they had been hired. PRL and TSH values were reduced after 1 year of work and were still reduced 6 months later. Further analyses showed a different behaviour: in fact the levels of the two hormones rose above the reference values, while the HGH and other gonadotropins showed no alterations. These results seem to indicate that at the start of exposure to aluminium concentrations below TLV-TWA there is an effect on the hypothalamus pituitary axis. This phenomenon is probably transient perhaps because of an adaptation mechanism. Further studies are however necessary to verify these results. PMID- 2593967 TI - Alpha 1-antitrypsin and lung function in cement workers. AB - The relationship between the serum concentration of alpha 1-antitrypsin (AAT), the concentration of dust at the workplace and lung function abnormalities was examined in 48 male workers occupationally exposed to cement dust. Measurements were performed in all subjects and included ventilatory volumes (FVC, FEV1), airway resistance (Raw), static lung volumes (RV, FRC, TLC), transfer factor for CO and AAT serum concentration. The relationship between lung function, smoking, respirable cement dust exposure, and AAT serum concentration was investigated by the method of multiple linear regression. A statistically significant correlation was observed between AAT blood concentration and respirable dust exposure. The contribution of respirable dust exposure to the description of AAT concentration was positive as was the contribution of Raw. The contributions of transfer CO, smoking and RV/TLC ratio were negative. All the variables considered accounted for approximately 30% of the total variability of the AAT concentration. To conclude, in cement workers the higher AAT serum concentration which is associated with a loss of lung function, and higher respirable cement dust concentration may be part of the defence mechanism against the potential proteolytic activity occurring in occupational dust exposure. PMID- 2593968 TI - [Evaluation of the effects on the nervous system from exposure to low concentrations of mercury in employees manufacturing fluorescent lights]. AB - In order to evaluate the effects of low inorganic mercury concentrations on workers employed in the manufacture of fluorescent lamps, a stratified sample of workers was selected at random and assigned to three groups according to the level of exposure. In all three groups, the urinary mercury values were within the normal range for unexposed population. Among the indicators of effect the simple reaction times test showed statistically significant differences between the three groups. Also "state anxiety" and "trait anxiety", investigated by the S.T.A.I. questionnaires, differed between the unexposed group and the other two. A positive correlation was found between simple reaction times and the state and trait anxiety scores in the whole sample and in the subsample of women. Moreover, the prevalence of symptoms related to low mercury exposure, collected by a questionnaire, was higher in the two exposed groups. Due to the absence of group differences for the urinary mercury levels, interpretation of the results is cumbersome. On the one hand it cannot be ruled out that the unexposed group (mainly white collar workers) had some characteristics which could explain the difference in the simple reaction times test and in anxiety. Conversely, if a true mercury effect does indeed exist, the similarity of the performance between the second and third groups (both consisting of exposed blue collar workers) could be explained if we assume that the high turn-over inside the factory could have caused a similar previous exposure to mercury vapours. PMID- 2593969 TI - Mortality in an area contaminated by TCDD following an industrial incident. AB - The mortality experience of the population, aged 20-74 years, living in an area contaminated by TCDD after an industrial accident in 1976, was examined in the period 1976-1986 and compared with the mortality of the population of the surrounding noncontaminated territory. People who left the area during the study period were followed up, and vital status was successfully ascertained for over 99% of the cohort members. An increased mortality, from chronic ischemic heart disease (males) and hypertensive disease (females), which could not be explained in terms of chance, confounding, or bias, was noted in the exposed population. The stressful experience of the population in the aftermath of the disaster was deemed relevant to the interpretation of these findings. Overall, cancer mortality was not increased. Suggestive increases, however, were seen for melanoma, brain cancer, soft tissue sarcomas and certain hematologic neoplasms, whereas mortality from breast cancer and cancer of the liver was noticeably decreased. Further research is in progress in order to thoroughly investigate the association, if any, of cancer occurrence with TCDD contamination. PMID- 2593970 TI - [Occupational arsine poisoning: description of a case]. AB - A case of occupational arsine poisoning is described that occurred in a small family workshop during blackening operations on zinc/aluminium alloy manufactured parts with acid solutions. This report shows that occupational poisonings wrongly believed to have disappeared can still occur, especially in small and often unsafe working environments. PMID- 2593971 TI - [Levels of the electromagnetic field in the vicinity of therapeutic devices using radiofrequency and microwaves]. AB - The paper presents the results of an analysis made on the electromagnetic field levels around RF and MW equipment used for medical purposes to achieve induced thermogenesis in body areas affected by disease. An irradiation diagram was constructed for some of the most widely used devices in clinical practice and measurements were made on RF devices to identify the influence of obstacles in determining electric field levels, such as accessories or persons present in the working environment. Electric field and power density levels were checked, as can be measured at a distance of 100 cm at identical selected power during a typical "lumbar-dorsal spine" treatment using different types of RF and MW devices, to identify the different degree of electromagnetic pollution that each of the devices causes. PMID- 2593972 TI - [Mortality: various measurements compared]. AB - SMR (Standardized Mortality Ratio) is a useful epidemiological measure but it cannot be computed when person-years distributions (denominators) are not available. In this situation PMR (Proportionate Mortality Ratio) and MOR (Mortality Odds Ratio) represent possible alternatives. Definitions of PMR and MOR are presented, and properties and drawbacks of these measures are discussed in relation to SMR's estimates. Fictitious data representing factual situations are used as working examples. PMID- 2593973 TI - [Professionalism in occupational medicine. Comments on a sentence]. PMID- 2593974 TI - Ibuprofen vs acetaminophen in children. PMID- 2593975 TI - Malathion for head lice. PMID- 2593976 TI - Prevention of bacterial endocarditis. PMID- 2593977 TI - [The effect of liver cirrhosis on activation of the coagulation and fibrinolysis system and on coagulation inhibitors]. AB - The activation of coagulation and fibrinolysis as well as coagulation inhibitors in the blood of patients with compensated (n = 25) and decompensated (n = 25) liver cirrhosis were studied. Protein C (PC) was decreased in a more pronounced manner than antithrombin III (AT III) in liver cirrhosis. Thereby, PC proved to be a highly sensible indicator of liver cell dysfunction. Decreased levels of PC activity (PC ratio activity/antigen 0.82) in decompensated liver cirrhosis suggest production of dysfunctional, undercarboxylated PC. We observed increased blood concentrations of fibrinopeptide A (FPA) (p less than 0.05) in both groups of patients compared to healthy volunteers (n = 25), while D-Dimer was increased only in patients with decompensated liver cirrhosis (p less than 0.01). Comparing both groups of patients. D-Dimer was significantly different with higher levels in decompensated liver cirrhosis (p less than 0.01). The ratio D-Dimer/FPA was significantly increased in decompensated liver cirrhosis compared to both other groups. These observations indicate that efflux from the extravascular space, e.g. ascitic fluid, contributes to the high contents of fibrin degradation products (D-Dimer) in patients with decompensated liver cirrhosis. In summary we conclude that patients with liver cirrhosis have enhanced activation of both coagulation and fibrinolysis but that the balance is not significantly displaced. PMID- 2593978 TI - [Diagnosis and therapy of hypercalcemic crisis]. AB - Between September 1985 and July 1988 at the Surgical Department of University Mainz 113 patients with primary or tertiary hyperparathyroidismus were operated. In four patients a hypercalcemic crisis developed. At the same time two patients with a hypercalcemia as a metabolic complication of cancer were treated. Within a few hours an involution of the life-threatening symptoms could be achieved by rehydration and diuresis at our intensive care unit. The treatment with mithramycin, calcitonin, a hemodialysis or a phosphate infusion were necessary in none of our patients. Because of the prompt starting of those therapeutical treatments at the intensive care unit no patients died as a result of the hypercalcemic crisis. After ending the hypercalcemic crisis the patients with hyperparathyroidismus were operated. In the patients with a hyperparathyroidismus associated with carcinoma a therapy to lower serum calcium with cortisone and calcitonin was performed. PMID- 2593979 TI - [Morton metatarsalgia]. AB - Four cases of Morton's metatarsalgia are presented. In all cases history and clinical findings were typical. The duration of the disease until the assessment of the final diagnosis with an average of three years was very long. Conservative treatment in all cases was unsuccessful, operative excision of the neuroma resulted in complete relief of pain. PMID- 2593980 TI - Acute exposure to maneb alters some behavioral functions in the mouse. AB - Maneb, an organomanganese fungicide, is largely used in agricultural regions for control of field crop pathologies. Despite its apparent low toxicity, there are reports showing that maneb has harmful effects on peripheral and central nervous systems. In this work the effects of acute administration of maneb were studied on some experimental animal models. Male adult mice were treated with several doses of maneb, IP, and submitted to gross behavioral observation (200-1000 mg/kg) and measurement of locomotor activity, barbiturate-induced sleeping time, isolation-induced aggressiveness, catatonia, climbing behavior and of rota-rod performance (30, 60 and 100 mg/kg). The results showed that maneb has an inhibitory effect on locomotor activity and aggressiveness and increases barbiturate-induced sleeping time and haloperidol-induced catatonia. However, maneb did not affect the apomorphine-induced climbing behavior of animals. These data indicate that maneb has a CNS depressant-like effect, and suggest, at least partially, the involvement of dopaminergic systems in the mediation of this effect. PMID- 2593981 TI - Short-term effects of paraoxon and atropine on schedule-controlled behavior in rats. AB - The effects of lethal (2.0 mg/kg) and high sublethal (1.3 mg/kg) dosages of the organophosphate acetylcholinesterase (AChE) inhibitor paraoxon on FR10 performance rate was determined 1 and 2 days after intoxication. The lethal doses were antidoted with either centrally acting atropine sulfate (AS), or atropine methyl bromide (AMB) or atropine methyl nitrate (AMN), both quaternary salts and not expected to act centrally. AChE inhibition in the brain was about 35-60% on the second day after treatment. AS yielded a small transient depression in performance, while AMB and AMN yielded severe deficits, with incomplete recovery. Performance was depressed by 1.3 mg/kg paraoxon by 52% and 34% on days 1 and 2, respectively, while performance was more greatly depressed by the lethal dose, especially with the noncentrally acting antidotes: AS, 67 and 48%; AMB, 81 and 55%; AMN, 91 and 78%. However, a low dose of AS with 2 mg/kg paraoxon resulted in very severe, nonrecovering deficits. A lethal dose of the nonpersistent anti-AChE eserine sulfate, antidoted with a low dose of AS, yielded no deficits. Thus, a high level, acute intoxication with paraoxon yields behavioral deficits which are attenuated by high levels of a centrally acting muscarinic receptor antagonist. The paraoxon-induced performance deficits or their recovery do not correlate directly with AChE inhibition. PMID- 2593982 TI - The effect of low level lead exposure on the postnatal structuring of the rat cerebellum. AB - Exposure of rat pups to lead (less than 45 micrograms/dl blood) caused no alterations in the rate of cerebellar cell acquisition, migration or final number when compared with age-matched controls. The rate of DNA biosynthesis was higher in the lead-exposed animals compared to controls and remained elevated until postnatal day 10. This observation suggests lengthening of the cell cycle. The expected increase in DNA biosynthetic rate was delayed in neuron-enriched fractions obtained from lead-exposed pups. This may have been due to the isolation procedure specifically selecting internal granular layer cells which migrated precociously during a protracted G1 phase in a lead-impaired cell cycle. Morphometric studies revealed no difference in the number, viability and migration of cells within and from the external granular layer of the cerebellum of lead-exposed animals. It is concluded that chronic low level lead exposure has no significant effect on the early structuring of the developing cerebellum. PMID- 2593983 TI - Behavioral and neuroanatomical sequelae of prenatal naloxone administration in the rat. AB - Pregnant Long-Evans hooded rats were dosed subcutaneously with 1 or 5 mg/kg/day naloxone hydrochloride, or an equal volume of vehicle, from gestational Day 4 (GD4) through GD19. Offspring were assessed for development of righting reflex, negative geotaxis, and open field activity, and for acquisition of a Warden maze; offspring sacrificed at postnatal Day (PND) 21 were assessed for several parameters of cerebellar, hippocampal, and motor cortical morphology. Five mg/kg/day naloxone accelerated development of negative geotaxis and righting reflex, while 1 mg/kg/day naloxone tended to slow development. Low dose females had significantly more errors than controls on the first day of maze learning. The high dose group had a significantly higher concentration of granule cells in the curvature of the dentate gyrus than controls; other neuroanatomical measures were unaffected by dosing. These findings confirm and extend previous work indicating that prenatal exposure to naloxone may alter neurobehavioral development in the rat. PMID- 2593984 TI - Effects of carbon monoxide in combination with behaviorally active drugs on fixed ratio performance in the mouse. AB - The effects of carbon monoxide (3.75, 7.5, 15 and 30 ml/kg, IP) alone and in combination with ethanol (1.1 g/kg), nicotine (1.1 mg/kg), caffeine (36.1 mg/kg), chlorpromazine (2.2 mg/kg), diazepam (10 mg/kg), pentobarbital (23.1 mg/kg), d amphetamine (1.4 mg/kg) or morphine (13.3 mg/kg) were evaluated in mice. Animals were trained to lever press under a fixed-ratio 32 schedule of water reinforcement. Response rates following CO-drug combinations were compared with the expected additive effects determined by the sum of the effects of each agent administered alone. CO (15 and 30 ml/kg) in combination with ethanol produced supra-additive effects. CO-chlorpromazine and CO-d-amphetamine combinations often produced greater than additive response-rate suppression, although differences from additivity did not reach statistical significance. The effects on response rates following CO in combination with nicotine, caffeine, diazepam, pentobarbital, or morphine were additive. These results suggest that concurrent use of therapeutic or abused drugs and CO exposure may place an individual at higher risk for behavioral toxicity. PMID- 2593985 TI - Neurotoxicological effects of trimethyltin on the stellate ganglion. AB - Hamsters treated with trimethyltin (TMT), 3 or 4 mg/kg IP, developed neurological symptoms, including tremor, within 24 hours. Postganglionic action potentials were recorded from isolated stellate ganglia of untreated hamsters (control ganglia) and TMT-treated hamsters (TMT ganglia). Compound action potentials (nicotinic transmission) of control and TMT ganglia were not significantly different. The afterdischarges induced by preganglionic stimulation at 30 Hz for 2 sec in the presence of 10(-3) M hexamethonium (muscarinic transmission) were significantly smaller in TMT ganglia than in control ganglia. The discharges induced by the muscarinic cholinoceptor agonist. McN-A-343, were also smaller in the TMT ganglia. Two other muscarinic processes, posttetanic potentiation and potentiation of the compound action potential by McN-A-343, were not significantly reduced in the TMT ganglia. Morphological studies of the ganglia revealed marked changes in the TMT ganglia with severe neuronal degeneration including vacuole formations and accumulations of lysosomes in the cytoplasm. These results demonstrate that TMT has marked anatomical effects on the stellate ganglion that may lead to the reduction in muscarinic cholinergic transmission. PMID- 2593986 TI - Neurobehavioral effects of prenatal alcohol: Part I. Research strategy. AB - This paper, Part I of a three-part series, reviews the literature on the neurobehavioral effects of prenatal alcohol exposure and describes a large group of tests assembled to assess neurobehavioral outcomes of alcohol teratogenesis in 7-year-old children. This paper presents the distribution of these test scores for our sample and discusses their relationships with an alcohol binge score and with full-scale IQ. This group of tests is suitable for children with a wide range of abilities and provides a broad assessment of neurobehavioral deficits. Part II of this series describes a new method of statistical analysis, Partial Least Squares (PLS), which is particularly well suited to complex multivariate data sets such as these, and with its aid, examines the effects of prenatal alcohol exposure on IQ, achievement, vigilance and classroom behavior, a total of 43 outcome scores. Part III examines prenatal alcohol effects on outcomes from the broad group of 164 scores deriving from 17 neuropsychologic tests, using the Partial Least Squares methodology, and summarizes the implications of our findings for the behavioral teratology of alcohol. PMID- 2593987 TI - Neurobehavioral effects of prenatal alcohol: Part II. Partial least squares analysis. AB - This paper, the second in a series of three, introduces Partial Least Squares (PLS) methods for assessing the effects of moderate levels of prenatal alcohol exposure on performance and behavior in young school-age children. Studies of human behavioral teratology pose statistical problems for which standard multiple regression methods are inadequate. Prenatal alcohol exposure, the teratogenic "dose," can be assessed only indirectly through a variety of measures of alcohol consumption. Similarly, the behavioral outcomes we examine--IQ, achievement, classroom behavior, and vigilance--are each measured indirectly in terms of multiple items or indicators. We find that a single latent variable, estimated as a linear combination of the measures of alcohol consumption, provides an appropriate measure of "dose" for summarizing the relationships between alcohol exposure and each of the four blocks of outcome variables. A pattern of alcohol consumption emphasizing binge behavior (i.e., reporting average consumption of multiple drinks per drinking occasion, or at least five drinks on any single occasion) in the period prior to recognition of pregnancy is significantly correlated with latent variables computed from each of the four outcome blocks: IQ, academic achievement, classroom behavior and attention/vigilance. PMID- 2593989 TI - The effects of cadmium on the self-administration of ethanol and an isocaloric/isohedonic equivalent. AB - During a period of baseline fluid intake recording, adult male rats were presented with a three-bottle, two-fluid choice test that offered either a 10% ethanol solution (v/v) and tap water as alternatives, or a sucrose/quinine solution and tap water as alternatives. The sucrose/quinine solution was equivalent to the ethanol solution both in terms of calories and palatability. After intakes stabilized, half of the animals from each test condition were placed on a diet containing 100 ppm cadmium and the remaining half of the animals were placed on a standard laboratory diet. After 60 days of exposure to their respective diets, all animals were presented their earlier test solutions, both in a nonchoice and choice format. The results from the choice test indicated that although cadmium treatment did not produce a clear preference for ethanol over water, cadmium exposure was associated with a significant increase in ethanol consumption. Moreover, the self-administration of the isocaloric/isohedonic equivalent (sucrose/quinine solution) was unaffected by cadmium contamination. These data are discussed in terms of their implications for both nutritional and sensory-impairment accounts of metal-related changes in the volitional intake of ethanol. PMID- 2593988 TI - Neurobehavioral effects of prenatal alcohol: Part III. PLS analyses of neuropsychologic tests. AB - This paper is the third in a three-part series describing an investigation of the effects of prenatal alcohol exposure on the neurobehavioral functioning of 384 children about 7 1/2 years old. Here we describe the use of Partial Least Squares for data reduction and analysis of 158 neurobehavioral measures as they relate to 13 aspects of prenatal alcohol exposure. A general alcohol latent variable, emphasizing both binge and regular drinking patterns in the period prior to pregnancy recognition as well as during pregnancy, predicts a pattern of neurobehavioral deficit that includes attentional and memory deficits across both verbal and visual modalities; a variety of "process" variables reflecting poor integration and quality of responses; behavior patterns involving distractibility and poor organization; and an inflexible approach to problem-solving. The prominence of poorer spatial organization and arithmetic as primary outcomes of alcohol teratogenesis suggests a possible "nonverbal learning disability" pattern of deficit associated with prenatal alcohol exposure at the level of social drinking. PMID- 2593992 TI - An anticipatory support program for high-risk parents: follow-up results. PMID- 2593991 TI - Low-birthweight infants and rehospitalization: what's the incidence? PMID- 2593990 TI - Postnatal function following prenatal reserpine exposure in rats: neurobehavioral toxicity. AB - Behavioral and neurochemical analyses were conducted on preweanling CD rats prenatally exposed to either 0, 0.375 or 0.750 mg/kg/day reserpine SC on gestation days 12-15. Offspring body weights were taken on test days, and pups were tested for negative geotaxis responding on postnatal day 8, developmental activity on days 12, 16 and 20, and auditory startle habituation on day 19 or 20. In addition, brains were removed from culled pups on day 1, 1 male and 1 female/litter on day 8, and animals tested for activity on day 21. Neurochemical assays were performed on whole brains from 1- and 8-day-old pups, and on caudate nucleus, frontal cortex and hippocampus of day 21 rats. Treatment resulted in dose-related decreases in maternal weight gain over gestation and mean pup weight at birth. Changes in the normal developmental activity pattern were both sex and dose dependent in treated rats. In auditory startle habituation experiments, rats exhibited a dose-related decrease in response amplitude and rate of habituation. In the day 21 females, caudate nucleus dopamine (DA) and serotonin (5-HT) concentrations and DA-receptor binding were decreased in a dose-dependent manner. Males showed less dramatic, but similar trends in caudate changes. However, hippocampal 5-HT and 5-HT receptor binding were significantly reduced only in females. Thus, sex-related behavioral alterations were accompanied by sex-related neurochemical changes, and females generally were more affected than males by prenatal reserpine treatment. The significant decrease in activity and auditory startle amplitude in the females is consistent with the suggested down regulation of the DA system in regional brain areas. PMID- 2593993 TI - The nurse expert witness: professional implications. PMID- 2593994 TI - Reliability of head circumference measurements for preterm infants. PMID- 2593996 TI - Education for advanced practice neonatal nurse practitioners in patient management roles. PMID- 2593995 TI - Appraisal and caregiving for the drug addicted infant. PMID- 2593997 TI - Rh hemolytic disease of the newborn. PMID- 2593998 TI - Epinephrine. PMID- 2593999 TI - [Experimental study on the changes in circulatory kinetics due to an increase of intraabdominal pressure: the effective monitoring of the pressure of inferior vena cava]. AB - We examined the change in circulatory kinetics due to an increase in intraabdominal pressure by adding pressure quantitatively to the abdominal wall by means of the manchette technique by using mongrel dogs, and obtained the following results: 1) By adding to the pressure to the abdominal wall, the pressure of inferior vena cava at the confluence of right and left common iliac veins showed a significantly higher value (p less than 0.05) than those at other 4 areas of the vena cava from just above the diaphragm to the above confluence. 2) All the dogs in the group with 20mmHg pressure survived for 24 hours, while those in the group with 40mmHg pressure died in all after survival between 13.8 +/- 2.05 hours. 3) The pressures of the inferior vena cava at the confluence of right and left common iliac veins with 20 and 40mmHg showed no significant difference immediately after the pressurization, but thereafter showed a increasing tendency in the group with 40mmHg (p less than 0.05). This increase in the pressure of the inferior vena cava lead to peripheral circulatory insufficiency. 4) The measurement of the pressure of the inferior vena cava at the confluence of right and left iliac veins in case of increased intraabdominal pressure seems to be an effective index for the risk of intraabdominal pressure. PMID- 2594001 TI - [Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibodies]. AB - Aiming at radioimmunodetection of colorectal cancer, anti-CEA monoclonal antibodies (CEA102) were produced by immunization with purified CEA. CEA102 showed high specificity with colorectal cancer by mixed hemadsorption assay and immunoperoxidase technique. The antigen detected by CEA102 was confirmed to be carcinoembryonic antigen (CEA) and its molecular weight was estimated to be ca. 180,000 by biochemical analysis. The in vivo study using nude mice grafted a human colorectal cancer or a human malignant melanoma showed greater accumulation of 125I-labeled CEA102 in CEA-positive colorectal cancer than in nude mouse tissues and CEA-negative malignant melanoma. Moreover we successfully obtained scans with good localization of the grafted colorectal cancer on FCR (Fuji Computed Radiography). Using 131I-labeled CEA102 liver metastasis in the patient with colorectal cancer was successfully detected by external scanning with gamma camera. These results suggest that radiolabeled CEA102 is useful for the detection of colorectal cancer. PMID- 2594000 TI - [Evaluation of the gastroesophageal reflux (GER) in infancy analysed with the subscore of the continuous lower esophageal pH monitoring (pH-monitoring)]. AB - Since GER in infancy tends to disappear as patients grow, operation should be selected carefully. Data of the pH-monitoring collected from 114 cases for last 8 years were analysed. Thirty five cases were observed without operation in view of their younger age (under 6 months) or mild degree of GER evaluated on the basis of clinical signs, radiological, manometric, pH-metric and fiberscopic examination. Four in 5 aggravating cases were compared with 8 improving cases selected from the non-operated 60 cases. The four pH-subscores calculated by Johnson's method were compared between 2 groups. The means and standard deviations of the subscores of the number of the pH less than 4.0 greater in duration than 5 min. were 42.4 +/- 14.791 in the aggravating and 5.7 +/- 0.766 in the improving: those of the duration of the longest episode of pH less than 4.0 were 7.4 +/- 1.996 and 2.5 +/- 0.335. Difference between the both subscores were statistically significant (p less than 0.05). Therefore those subscores can be used as a parameter by which early operation may be chosen rather than subjecting the patient to a prolonged no-operative treatment. PMID- 2594002 TI - [Immunohistochemical and clinicopathological studies of chromogranin immunoreactive cells in large bowel carcinoma]. AB - We examined the clinicopathological relevance of chromogranin immunoreactive cells in a well documented series of 212 large bowel cancer patients. Chromogranin immunoreactive cells were detected in 33.5% of the carcinomas, occurring either as rare cases (19.3%) or as diffuse cases (14.2%). The tumors with chromogranin immunoreactivity were associated with a more aggressive clinical course than tumors without immunoreactivity (Generalized-Wilcoxon; p less than 0.08). Moreover, the survival of patients with diffusely immunoreactive tumors was significantly shorter than that of patients without such cells (Generalized-Wilcoxon; p less than 0.009). Therefore, the study of chromogranin immunoreactivity in large bowel carcinomas may enable the identification of a subpopulation of colorectal carcinomas associated with a relatively poor prognosis. PMID- 2594003 TI - [Extracorporeal adriamycin-removal following hepatic artery infusion: use of direct hemoperfusion combined with veno-venous bypass]. AB - Systemic toxicity of adriamycin (ADR) has limited its high dosage application in hepatic artery infusion. We developed a new extracorporeal device combining direct hemoperfusion (DHP) and veno-venous bypass to eliminate ADR following hepatic artery infusion. Mongrel dogs were divided into three group, I: controls without DHP (n = 3), II: DHP under single venous bypass from IVC to left external jugular vein (n = 3) and III: DHP under hepatic venous isolation using veno venous bypass (n = 5). Blood specimens were obtained to determine plasma drug levels until 60 min after ADR injection (3 mg/kg body weight, 1 min). Blood flow through DHP, which was averaged 200 ml/min in both groups II and III, was monitored with ultrasonic flowmeter. In groups I and II, peripheral ADR levels rapidly increased, reaching the peak values of 5.61 +/- 2.42 and 1.17 +/- 0.31 micrograms/ml respectively at 1 min after injection. The peak level in group III was markedly reduced, the value being 0.42 +/- 0.17 microgram/ml, which was 7.5% of the peak value of group I. The removal rates in groups II and III were 10.9 and 27.5% respectively. In conclusion, DHP under hepatic venous isolation can be an useful method to reduce systemic distribution of ADR during hepatic artery infusion. PMID- 2594004 TI - [Viability assay for liver transplantation]. AB - Various parameters were investigated to know whether a viability assay before liver transplantation was possible. Two series of experiment were performed. The first consisted of 2 groups of ischemically injured canine livers which had definitely different viability. GPT, bilirubin, lactate pyruvate ratio, ketone body ratio ammonium in the perfusate, hepatic tissue flow, and hepatic tissue oxygen consumption were measured during hypothermic machine perfusion at 6 degree C. As a result, tissue flow and tissue oxygen consumption were found to be good parameters because they indicated the viabilities of the isolated liver grafts accurately and instantly in the both groups. In the second series, 9 ischemically injured canine livers were hypothermically perfused to assay their viability and orthotopically transplanted. In the cases that the oxygen consumption was below 3.0 mumol/min./100g, no grafts sustained the lives of the recipients. We concluded that if we measure the oxygen consumption of hypothermically perfused livers, we can eliminate the low viability livers before transplantation and avoid primary graft non-function. PMID- 2594005 TI - [Changes in hepatic and renal tissue blood flows in cirrhotic rat in hemorrhagic shock]. AB - The purpose of present study is to elucidate the influence of hypotension on hepatic and renal tissue circulations in cirrhosis. The changes of hepatic and renal tissue blood flows (TBF) were studied in hemorrhagic shock using cirrhotic rats. The hepatic and renal energy charges (EC) were measured in normal and cirrhotic rats. Hepatic TBFs of the cirrhotic rats decreased to 74% of the normal, portal pressure increased to 140%, but renal TBF was not changed significantly. In hemorrhagic shock induced by blood exsanguination, hepatic and renal TBFs of normal rats were restored to the preshock levels by transfusion of shed blood, but those of cirrhotic rats were not restored. Furthermore, the hepatic and renal ECs of normal-shocked rats were not different from those of control rats, but the ECs of cirrhotic-shocked rats were decreased significantly. These findings suggest that hypotension under cirrhosis disturbs hepatic and renal tissue circulations and energy metabolisms also in a period of after-shock phase. PMID- 2594006 TI - [The management of chest injuries]. AB - The mortality from chest injuries is so high due to severe physiologic imbalance that an immediate and accurate diagnosis of the injured organ and prompt treatment can salvage the patient from the strategy. This study comprises 1329 injured cases including 145 patients with crushed chests. The cause of injury was traffic accident in 537 cases (40.5%), fall or degradation in 332 cases (25%). There was a correlation between the cause of injury and age, as that traffic accident was a major one in young aged and fall in elders. Treatment against crushed patients included 150 surgical operations, 206 plaster bandages, 56 drainage of thoracic, peritoneal and cranial cavities. Thoracotomies performed in patients with flail chest (2), lung contusion (4), rupture of the bronchi and diaphragm (each 1) and for evacuation of clotted hemothorax in 3 patients. The prognosis of all these patients was good. Lastly we conclude that since the prognosis of injured patients depends on how fast the patient can be carried to the hospital and how quickly the physician or surgeon can evaluate the trauma and institute a prompt treatment, the education of the primary staff is the most important. PMID- 2594007 TI - [An experimental study of tissue injury associated with reperfusion in ischemic limbs]. AB - Twenty adult mongrel dogs were divided into three groups. Group I: control (n = 7), group II: limb ischemia for 6 hours followed by reperfusion (n = 6), and group III: administration of alpha-tocopherol after 6 hours of ischemia, and reperfusion (n = 7). In group II, serum CPK and LPO increased after reperfusion with peak levels of 38,000 +/- 9,800 mU/ml and 20.4 +/- 3.7 nmol/ml respectively, which were significantly higher than those in group I. (CPK: p less than 0.02, LPO less than 0.03). In group III, the peak levels of serum CPK and LPO were regulated to the low level of 1,060 +/- 290 mU/ml and 9.2 +/- 4.5nmol/ml, respectively, which were significantly lower than those in group II. (CPK: p less than 0.02, LPO less than 0.04). Additional 13 dogs were divided into two groups in order to assess tissue LPO in the limb, liver, and kidney. Group A: control (n = 5), group B: reperfusion after 6 hours of ischemia (n = 8). Tissue LPO level of 1.89 +/- 0.74nmol/mg-protein in the gastrocnemius muscle in group B was significantly higher than that in group A (p less than 0.02), although there was no significant difference in the gracilis muscle, liver, and kidney. These results prove indirectly the participation of lipid peroxidative reaction by active oxygen in the mechanism of development of reperfusion injury, and suggest the preventive effect of alpha-tocopherol to reperfusion injury. PMID- 2594008 TI - [A case of hemosuccus pancreaticus associated with chronic pancreatitis]. AB - The term "hemosuccus pancreaticus" was coined by Sandblom in 1970, to describe a syndrome manifested by massive gastrointestinal hemorrhage through the pancreatic duct and the ampulla of water. A case of hemosuccus pancreaticus which had no hematemesis and melena is reported in comparison with two previously experienced cases. A 68-year-old alcoholic man was referred to Eiju General Hospital for poor appetite and occasional colicky pain in left epigastrium. Abdominal angiography and computed tomography revealed an aneurysm at the tail of the pancreas and hemosuccus pancreaticus caused by true aneurysm was strongly suspected. Laparotomy revealed chronic pancreatitis and a pancreatic pseudocyst at the tail of the pancreas that was considered to be the cause of the pain. Resection of pancreatic tail and splenectomy was performed without complication. Histopathological diagnosis of the resected pancreas was chronic pancreatitis. He has complained no abdominal pain and melena for 6 months after operation. PMID- 2594009 TI - [DNA damage and hepatic regeneration after partial hepatectomy: preliminary report]. PMID- 2594010 TI - [Morphological study on aspiration cytology of breast cancer--relationship to prognosis and malignancy grade: preliminary report]. PMID- 2594011 TI - [Functional evaluation of upper esophageal sphincter after subtotal esophagectomy in esophageal cancer: preliminary report]. PMID- 2594012 TI - [Relation between tumor necrosis factor secretion activity and serum FDP level in cancer patients: preliminary report]. PMID- 2594013 TI - [Monoclonal antibody KYSM-1 and immuno-histological specificity against esophageal cancer: preliminary report]. PMID- 2594014 TI - [The receptor status between in primary tumor and in its involved regional node referring to estrogen receptor and epidermal growth factor receptor in human breast cancer: preliminary report]. PMID- 2594015 TI - Structural characteristics influencing the carrier function of synthetic branched polypeptides based on poly[Lys-(DL-Ala)3)]backbone. AB - Effective carrier function of selected representatives of new branched polypeptides covalently coupled with the synthetic monovalent hapten, oxazolone was studied. The effectiveness of oxazolone-synthetic polypeptide conjugates in inducing oxazolone-as well as carrier-specific antibody responses in inbred mice was compared to that of bovine serum albumin (BSA)- and KLH-oxazolone conjugates. The synthetic polypeptides, poly[Lys-(D-Leui-DL-Alam)] (D-LAK), LAK and FAK, as well as the common poly[Lys-(DL-Alam)](AK) core covalently coupled to oxazolone (Ox) induced a T cell-dependent antibody response when repeatedly administered with or without Freund's adjuvant in mice. This was evidenced by: the increasing titer of oxazolone-specific IgG during the course of the memory response; the appearance of all IgG subclasses; the effective oxazolone-specific priming by the conjugates; and the induction of an intense oxazolone- and carrier-specific DTH reaction. Although the oxazolone-specific antibody response was 10-100 times lower than that induced by KLH- or BSA-oxazolone conjugates, it was accompanied by a lower level or no detectable carrier-specific antibody response despite an effective carrier-specific T cell-mediated response. Significant differences were observed between the effectiveness of synthetic polypeptides used as carrier: highest oxazolone-specific antibody titers were observed using the AK, LAK and FAK conjugates. The intensity and specificity of the DTH reaction and antibody response induced by the carrier-oxazolone conjugates suggested that the distinct effectiveness of L- and D-amino acid-containing conjugates (LAK vs D-LAK and FAK vs D-FAK) was dependent on altered B cell recognition of the haptenic group. Circular dichroism (CD) spectra indicating different local orientation of oxazolone, when coupled to L or D side chain-terminating amino acids, support this suggestion. PMID- 2594016 TI - 1,25-Dihydroxyvitamin-D3 regulation of interleukin-2 and interleukin-2 receptor levels and gene expression in human T cells. AB - 1,25-Dihydroxyvitamin-D3 (1,25-D3) is known to inhibit DNA synthesis, immunoglobulin and lymphokine production [interleukin-2 (IL-2), gamma interferon (G-IFN), and granulocyte-monocyte colony-stimulating factor (GM-CSF)] by mitogen stimulated human peripheral blood mononuclear cells (PBMCs). Recent data suggest these inhibitory effects are mediated at the gene level through inhibition of mRNA accumulation of specific lymphokines in the activated cells. In previous studies, we have demonstrated the CD8+ T cell population was less sensitive to the anti-proliferative actions of 1,25-D3 than CD4+ T cells. The purpose of this investigation was to further assess ability of 1,25-D3 to regulate CD4+ and CD8+ T cell functions. Initial experiments showed that 1,25-D3 inhibited both IL-2 production and mRNA accumulation in mitogen-stimulated PBMC. However, IL-2 receptor (IL-2R) expression and mRNA accumulation in stimulated PBMC was not affected by 1,25-D3. Both FACS sorted CD4+ and CD8+ T cells expressed IL-2R equally upon stimulation and neither showed an inhibitory effect on this expression by 1,25-D3. Human CD4+ and CD8+ T cells showed a stimulus-specific production of IL-2. CD4+ cells stimulated with mitogen and HLA-DR positive accessory cells produced measurable levels of IL-2 that were completely inhibited by 1,25-D3. CD8+ T cells did not generate measurable amounts of IL-2 in this system. However, CD4+ and CD8+ T cells produced large amounts of IL-2 when stimulated with mitogen and a protein kinase C activator, phorbol myristate acetate (PMA). Under these circumstances, both CD4+ and CD8+ T cell IL-2 production was inhibited completely by 1,25-D3. These data suggest that IL-2R expression in PBMCs and T cell subsets is equal and unaffected by 1,25-D3 while IL-2 production in T cell subsets is stimulus-specific and completely inhibited by 1,25-D3. PMID- 2594017 TI - A substantial proportion of the adult BALB/c available B cell repertoire consists of multireactive B cells. AB - A variety of studies have documented multireactive antibodies in both the preimmune and naturally activated repertoire, but the relationship of these primarily IgM multireactive antibodies to antigen-specific primary and secondary response antibodies is currently not defined. In order to characterize the BALB/c preimmunization specificity repertoire and the baseline of naturally activated antibodies from which the immune response to a specific antigen (hen egg-white lysozyme, HEL) develops, panels of polyclonally activated blast-derived hybridomas (BlAbs) and natural antibody hybridomas (NAbs) from the spleens of unimmunized mice were screened for binding to a panel of nine complex antigens. Over half of the IgM-secreting BlAbs produced antibodies that were antigen reactive; of these, over half were multireactive, i.e. capable of binding more than one complex antigen. There was no bias towards self vs foreign or thymus dependent vs thymus-independent antigens. The frequency of antigen-reactive NAbs was about half the frequency of antigen-reactive antibodies found among the BlAbs. However, over half of the antigen-reactive NAbs were also multireactive, and the reactivity profile within the antigen-reactive subset of NAbs was similar to that within the antigen-reactive subset of BlAbs. These results suggest that the available repertoire of adult spleen cells contains a high proportion of multireactive antibodies, and that a subset of the available repertoire is randomly activated, yielding a small proportion of natural antibodies which closely reflect a random sampling of the available repertoire. Although monospecific precursor cells are rare, monospecific IgM BlAbs were found for all antigens in the panel except staphylococcal nuclease and mouse IgG. Monospecific as well as multireactive HEL-binding BlAbs were found at frequencies comparable to other protein antigens in the panel, and HEL-reactive NAbs were also present. On the other hand, it has previously been shown that HEL-reactive IgM antibodies (including multireactive antibodies whose specificities include HEL) are rare or absent in both the primary and secondary response to HEL. This cannot be attributed to an absence of available precursor B cells, and most likely reflects an early recruitment of HEL-reactive clones into the peripheral B cell pool. The possibility that polyreactive B cells may serve as precursors for some HEL specific IgG antibodies is discussed. PMID- 2594018 TI - Altered production and renewal of natural killer cells in B-lymphocyte-deficient CBA/N mice. AB - The present study was designed to measure by quantitative and kinetic methods the production and renewal of natural killer (NK) cells in congenitally B-lymphocyte deficient (CBA/N) mice. The total NK activity (percent specific lysis corrected for changes in whole organ cellularity) of the bone marrow and spleen of immunologically normal (CBA/CaJ) and CBA/N mice was assayed prior to and immediately after 48 h treatment (2 X/day, i.p.) with the cell cycle poison hydroxyurea (HU) and at various intervals throughout the subsequent post-HU recovery period. The total NK activity (TNKA) of untreated CBA/N bone marrow was 154% of that of CBA/CaJ bone marrow while the TNKA of CBA/N spleen was not significantly different (112%) from that of CBA/CaJ spleen. At the conclusion of 48 h HU, bone marrow TNKA of CBA/N and CBA/CaJ mice fell to 60 and 49%, respectively, of their saline-injected (2 X/day, i.p.) control levels, while spleen TNKA fell to 42 and 61%, respectively, of their saline-injected control levels. In the bone marrow, NK cell depletion in response to HU was more rapid in CBA/N mice (day 0.5 after HU) than in CBA/CaJ mice (day 2 after HU). TNKA of the spleen also decreased more rapidly in CBA/N mice (day 2 after HU) than in CBA/CaJ mice (day 3 after HU). The data indicate an enhanced production and turnover of NK cells in CBA/N mice relative to CBA/CaJ mice. Moreover, increased production and renewal of NK cells in CBA/N mice together with virtually unchanged levels of NK activity (112% of CBA/CaJ mice) in CBA/N mouse spleens indicate that mature lytic NK cells in CBA/N spleen but not bone marrow have a significantly shorter post-mitotic life span than do NK cells in the spleens of immunologically normal (CBA/CaJ) mice. PMID- 2594019 TI - [Basic emotions. Phenomenology, psychodynamics, EEG spectral analysis]. PMID- 2594020 TI - [In vivo migration of peritoneal macrophages, saturated with fats in vitro]. AB - Our experiments aimed at the in vitro development of cells similar to macrophage foam cells of vessel wall. Fatty macrophages were produced by Intralipid incubation of peritoneal macrophages and their motility was studied in vivo. Our results showed that fat-saturated, isotope and colloid-gold marked macrophages can get through the vessel wall, so they are able to in vivo migration. PMID- 2594021 TI - [Alpha-1-antitrypsin deficiency and liver diseases]. AB - Authors studied liver biopsy of hundred infants and young children. 15 livers were normal and three of 85 patients suffering from liver disease had liver changes associated with serious alpha--1-antitrypsin (AAT) deficiency (in two cases with portal fibrosis associated with inflammation, in one case with portal fibrosis associated with moderate active inflammation of reduction of intrahepatic biliary ducts). Typical positive, diastase resistant globules were in the hepatocytes of only one patient, but AAT could be demonstrated in periportal liver cells of all three patients by AAT specific immuneperoxidase method. Of 830 hepatic cirrhosises in adult age, in eight cases PAS positive, diastase-resistant AAT immunreactive globules occurred in periportal hepatocytes, suggesting AAT deficiency; however, the AAT level and fenotype of these patients were not known. Examination of possibility of AAT deficiency should be performed in every case, where the cause of liver disease is unsolved; this examination is especially indicated by the presence of typical PAS positive, diastase-resistant, AAT immunreactive globules in hepatocytes. PMID- 2594022 TI - [Development of the avian and mammalian heart prior to the onset of blood circulation, studied in chick and mouse embryos]. AB - Heart development, its morphological and functional development prior the start of blood circulation were compared in chicken and mouse embryos. At beginning of neurula stage, when also somites appear, the cardiogenic mesoderm forms into tissue of epithelial type and cardiac plate is developed in wall of pleuroperitoneal cavity. In conjugated cardiac plate, primordial cardiac cavity fundaments appear in the about 30-hour old chicken embryo with 6-7 somites. First myoblasts (and spontaneous action potentials) can be observed in the ventricular part of embryos with 7 somites. Hence, muscular differentiation is expanded to atrial section. In embryo with 9-10 somites straight cardiac tube is developed, its ventricular section pulsates feebly, but it is unable for blood circulation yet. Pacemaker tissue of cardiac tube is in the atrium. At the end of second day the first curvature of heart appears and myocytes of venous sinus become pacemaker. At the end of neurula stage the blood circulation starts in two-day old embryo with 16 somites. Development of heart of mammalian embryos differs in several aspects from cardiac development of avian ambryos. In mammals transformation and differentiation of cells in cardiac plate and primordial cardiac fundaments have a cranio-caudal trend and in nearly same developmental stage as in chicken. In mouse circulation is started by curved cardiac tube of embryo with 10-12 somites (eight and half day old) at the end of neurala stage. PMID- 2594024 TI - [Glomerulonephritis in diabetics]. AB - Diagnosis of glomerulonephritis (GN) is rare among diabetics and few data relevant to this issue can be found in literature. In Institute of Pathology of "Szent-Gyorgyi Albert" University of Medicine the presence of GN was found in cases during the examination of renal biopsy material of 36 diabetics. All patients have suffered from diabetes mellitus of 2nd type and of less than 10 year existence, requiring no insulin treatment. In 2 cases diffuse diabetic glomerulosclerosis associated with GN. It is emphasized that kidney biopsy and its complex--light and electronmicroscopic and immunhistological--examination are essential to the diagnosis of GN of diabetics. PMID- 2594023 TI - [Mammosomatotropic cells in the pituitary gland of the rat with and without adenoma. Immunoelectron microscopic study]. AB - In non-tumorous adenohypophysis and in adenomas of adenohypophysis of rats the GN and PRL producing bihormonal mammosomatotroph cells were demonstrated by double marked immune-gold immuno-electronmicroscopic examinations. Cytogenesis and regulation of these cells are known, their clearing up is expected. Further examinations are needed to elicit, whether mammosototroph cells may occur also in nontumorous human adenohypophysises. PMID- 2594025 TI - [Morphologic changes in tubulo-interstitial diseases of the kidney]. AB - Morphological changes providing basis for the diagnosis of certain tubular interstitial diseases of kidney are surveyed in this paper. Different cylinders in tubular lumen, changes of tubular epithelium of endocytotic and of other origin and inflammatory cell reactions of interstice should be considered light microscopically. Immune histological examination of tubular basal membrane is essential for proper diagnosis. PMID- 2594026 TI - [Significance of plasma cells in the rejection of kidney grafts]. AB - Authors studied with immunohistochemical methods the immunoglobulin content of plasma cells during the rejection of renal grafts, in different rejections, in Cyclosporin-A nephro-toxicity and in chronic interstitial nephritis, as a comparison. By far the most plasma cells occurred in chronic rejection, containing more than 80% IgG. Whereas great majority of plasma cells were IgG positive in chronic interstitial nephritis. Probably, in chronic rejection a special, secondary type humoral immune reaction has a significant role in addition to cellular immune mechanisms. PMID- 2594027 TI - [Changes in chronic pancreatitis. Functional, structural and histological studies]. AB - Pancreatic function, structural changes in comparison with morphologic (histological) ones were studied in 22 patients suffering from chronic pancreatitis. Gravity of functional and structural damages--apart from minor differences--showed close cinnection with the severity of tissue alterations. In half of the cases, combination of tissue signs of obstructive and calcificating pancreatitis were observed, so it is considered gratuitous to separate sharply the two forms of chronic pancreatitis. PMID- 2594028 TI - [Morphologic studies of emdomyocardial biopsy specimens]. AB - Authors have studied 153 heart biopsies of 120 patients and results of 133 endomyocardial biopsies studied by light and electron microscopy are described. In addition to typical morphological picture of myocarditis, in majority of cases non-specific changes appearing also in idiopathic cardiomyopathy were observed and their ultrastructure is fully stated. Results are compared to relevant data of literature. Indications, informative value, practical and scientific research significance of myocardial biopsies are briefly overviewed. PMID- 2594029 TI - Oncogenic point mutations in the human retinoblastoma gene: their application to genetic counseling. AB - Mutations of the retinoblastoma gene, most of which cannot be detected by conventional Southern blotting, are known to cause both the nonhereditary and hereditary forms of retinoblastoma and have been implicated in the development of other cancers. Nonhereditary retinoblastoma is caused by a somatic mutation. Hereditary retinoblastoma is caused by a germ-cell mutation, most often a new one, and thus there is usually no family history of the disease. Unlike patients with the nonhereditary disease, those with the hereditary form are at risk for additional retinoblastomas, and their progeny are at risk for the tumors. We used a sensitive technique of primer-directed enzymatic amplification, followed by DNA sequence analysis, to identify mutations as small as a single nucleotide change in tumors from seven patients with simplex retinoblastoma (with no family history of the disease). In four patients the mutation involved only the tumor cells, and in three it involved normal somatic cells as well as tumor cells but was not found in either parent; thus, these mutations appeared to be new, germ-cell mutations. In addition, we found point mutations in cells from a bladder carcinoma, a small-cell carcinoma of the lung, and another retinoblastoma. We conclude that the technique that we have described can distinguish hereditary from nonhereditary retinoblastoma and that it is useful in risk estimation and genetic counseling. PMID- 2594030 TI - The diagnostic sensitivity of electrophysiologic testing in patients with syncope caused by transient bradycardia. AB - Although electrophysiologic testing accurately delineates abnormalities in patients with fixed cardiac-conduction defects, its sensitivity in identifying transient rhythm disturbances is unknown. We prospectively studied 21 patients who had electrocardiographically documented intermittent atrioventricular block (n = 13) or sinus pauses (n = 8) causing syncope, but whose cardiac rhythm had reverted to normal by the time of referral. There were 14 men and 7 women, with a mean age (+/- SD) of 63 +/- 13 years. Fourteen patients had organic heart disease, and 8 were taking cardioactive medications. Electrophysiologic testing was performed before the implantation of a permanent pacemaker. Only three of the eight patients with documented sinus pauses had abnormalities during their tests that suggested the correct diagnosis (sensitivity, 37.5 percent), including a prolonged sinus-node recovery time in one and carotid-sinus hypersensitivity in two. Three of the eight patients had abnormalities detected that were unrelated to syncope, including atrial flutter, dual atrioventricular nodal pathways, and sustained monomorphic ventricular tachycardia. Of the 13 patients with documented atrioventricular block, only 2 had abnormalities suggesting the correct diagnosis (sensitivity, 15.4 percent). Additional observations unrelated to syncope among these 13 patients included abnormal sinus-node function, atrial flutter, and atrial fibrillation causing hypotension. These preliminary observations suggest that a negative electrophysiologic test in a patient with a normal cardiac rhythm who has experienced syncope does not exclude a transient bradyarrhythmia as a cause of the syncope. Furthermore, electrophysiologic testing may sometimes reveal unrelated rhythm disturbances that may mistakenly be designated as the cause of the syncope. PMID- 2594031 TI - Hospital characteristics and mortality rates. AB - The Health Care Financing Administration (HCFA) publishes hospital mortality rates each year. We undertook a study to identify characteristics of hospitals associated with variations in these rates. To do so, we obtained data on 3100 hospitals from the 1986 HCFA mortality study and the American Hospital Association's 1986 annual survey of hospitals. The mortality rates were adjusted for each hospital's case mix and other characteristics of its patients. The mortality rate for all hospitalizations was 116 per 1000 patients. Adjusted mortality rates were significantly higher for for-profit hospitals (121 per 1000) and public hospitals (120 per 1000) than for private not-for-profit hospitals (114 per 1000; P less than 0.0001 for both comparisons). Osteopathic hospitals also had an adjusted mortality rate that was significantly higher than average (129 per 1000; P less than 0.0001). Private teaching hospitals had a significantly lower adjusted mortality rate (108 per 1000) than private nonteaching hospitals (116 per 1000; P less than 0.0001). Adjusted mortality rates were also compared for hospitals in the upper and lower fourths of the sample in terms of certain hospital characteristics. The mortality rates were 112 and 121 per 1000 for the hospitals in the upper and lower fourths, respectively, in terms of the percentage of physicians who were board-certified specialists (P less than 0.0001), 112 and 120 per 1000 for occupancy rate (P less than 0.0001), 113 and 120 per 1000 for payroll expenses per hospital bed (P less than 0.0001), and 113 and 119 per 1000 for the percentage of nurses who were registered (P less than 0.0001). PMID- 2594032 TI - National health insurance--the triumph of equivocation. PMID- 2594033 TI - Absence of effect of zidovudine on replication of hepatitis B virus in patients with chronic HIV and HBV infection. PMID- 2594034 TI - Pleural and retroperitoneal fibrosis from dihydroergotamine. PMID- 2594035 TI - Patients' wishes to forgo treatment versus institutional policies. PMID- 2594036 TI - Effect of vitamin D intake on seasonal variations in parathyroid hormone secretion in postmenopausal women. AB - Vitamin D intake should be sufficient to maintain calcium absorption and prevent increased parathyroid secretion throughout the year. To determine the level of intake that achieved the latter in elderly women, we studied the interrelations among vitamin D intake, serum 25-hydroxyvitamin D (25(OH)D) levels, and parathyroid hormone concentrations in a cross-sectional study of 333 healthy, white, postmenopausal women with low median calcium (408 mg a day) and vitamin D (112 IU a day) intakes who lived in Massachusetts. The overall inverse relation between serum parathyroid hormone and 25(OH)D levels was found to be dependent on vitamin D intake. In women whose estimated intake of vitamin D was less than or equal to 220 IU a day, the mean (+/- SD) serum parathyroid hormone values were lowest in those studied between August and October (30 +/- 11 ng per liter; n = 72) and highest in those studied between March and May (37 +/- 16 ng per liter; n = 54); the respective serum 25(OH)D levels were 93 +/- 32 and 63 +/- 21 nmol per liter. At vitamin D intakes of more than 220 IU a day, the mean serum parathyroid hormone and 25(OH)D levels did not vary with the season. The correlation between vitamin D intake and serum 25(OH)D concentration, although significant in all women (r = 0.29; P less than 0.001), was highest in those studied between March and May (r = 0.65; P less than 0.001) and lowest in those studied between August and October (r = 0.13; P greater than 0.10). The estimated serum 25(OH)D level associated with a vitamin D intake of 220 IU a day between March and May was 95 nmol per liter. Mean serum calcium values were similar at all times in both groups. We conclude that the dietary intake of more than 220 IU of vitamin D a day by postmenopausal women in Massachusetts may be sufficient to maintain constant serum 25(OH)D and parathyroid hormone concentrations throughout the year. Such an intake prevents a seasonal increase in parathyroid hormone secretion, with its possible deleterious skeletal effects. PMID- 2594037 TI - A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. AB - Mycosis fungoides is a T-cell lymphoma that arises in the skin and progresses at highly variable rates. Nonradomized studies have suggested that early aggressive therapy may improve the prognosis in this usually fatal disease. We studied 103 patients with mycosis fungoides, who, after complete staging, were randomly assigned to receive either combination therapy, consisting of 3000 cGy of electron-beam radiation to the skin combined with parenteral chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine (n = 52) or sequential topical treatment (n = 51). The prognostic factors were well balanced in the two groups. Combined therapy produced considerable toxicity: 12 patients required hospitalization for fever and transient neutropenia, 5 had congestive heart failure, and 2 were later found to have acute nonlymphocytic leukemia. Patients receiving combined therapy had a significantly higher rate of complete response, documented by biopsy, than patients receiving conservative therapy (38 percent vs. 18 percent; P = 0.032). After a median follow-up of 75 months, however, there was no significant difference between the treatment groups in disease-free or overall survival. We conclude that early aggressive therapy with radiation and chemotherapy does not improve the prognosis for patients with mycosis fungoides as compared with conservative treatment beginning with sequential topical therapies. PMID- 2594038 TI - Survival in children with perinatally acquired human immunodeficiency virus type 1 infection. AB - We describe our experience at Jackson Memorial Hospital in Miami, Florida, with 172 children who were given diagnoses of perinatally acquired infection with human immunodeficiency virus type 1 (HIV-1). The 146 mothers of the children acquired HIV-1 through heterosexual contact (69 percent), intravenous drug use (30 percent), or blood transfusion (1 percent). The children presented with symptomatic disease at a median age of eight months; only 21 percent presented after the age of two years. The most common first manifestations of disease were lymphoid interstitial pneumonia (in 17 percent), encephalopathy (in 12 percent), recurrent bacterial infections (in 10 percent), and candida esophagitis (in 8 percent), for which the median survival times from diagnosis were 72, 11, 50, and 12 months, respectively. Nine percent of the children had Pneumocystis carinii pneumonia at a median age of five months and had a median survival of only one month. The median survival for all 172 children was 38 months from the time of diagnosis. Mortality was highest in the first year of life (17 percent), and by proportional-hazard analysis the probability of long-term survival is low. In multivariate analyses, early age at diagnosis and the first identifiable pattern of clinical disease were found to be independently related to survival. We conclude that children with perinatally acquired HIV-1 infection have a very poor prognosis and that most become symptomatic before one year of age. Early diagnosis is important, since there is only a short interval in which to initiate prophylactic or antiviral treatment before progressive disease begins. PMID- 2594039 TI - Case records of the Massachusetts General Hospital. Case 52-1989. A 63-year-old man with osteomalacia and the later development of a right nasal mass. PMID- 2594040 TI - Mycosis fungoides: the therapeutic search continues. PMID- 2594041 TI - Physicians' health study: aspirin and primary prevention of coronary heart disease. PMID- 2594042 TI - The cardiovascular response to endotoxin. PMID- 2594043 TI - Potential long-term toxic effects in children treated for acute lymphoblastic leukemia. PMID- 2594044 TI - Calcitriol for osteitis fibrosa. PMID- 2594045 TI - Recovery of HIV at autopsy. PMID- 2594046 TI - Evaluation of acetylator phenotype, renal function and serum sulfadiazine levels in patients with paracoccidioidomycosis treated with cotrimazine (a combination of sulfadiazine and trimethoprim). AB - The authors evaluated the relationships among renal function, acetylator phenotype and serum sulfadiazine levels in 22 patients with paracoccidioidomycosis treated with 1 tablet of cotrimazine (a combination of 820 mg sulfadiazine and 180 mg trimethoprim) administered orally every 12 hours. Fifteen patients (68.18%) presented free sulfadiazine levels above 50 micrograms/ml, 6(27.28%) presented serum levels above 40 micrograms/ml, and 1(4.54%), levels lower than 40 micrograms/ml, this being the patient in which treatment failed. The highest free sulfadiazine levels were obtained in slow acetylator patients with reduced renal function. One patient with neuroparacoccidioidomycosis presented free sulfadiazine levels in cerebrospinal fluid corresponding to 55% of the serum levels. Finally, the authors consider cotrimazine to be an important therapeutic alternative for neuroparacoccidioidomycosis and conclude that administration every 12 hours can provide therapeutic sulfadiazine levels. They also suggest that when the sulfadiazine-trimethoprim combination is used, the therapeutic levels of sulfadiazine should be above 40 micrograms/ml. PMID- 2594047 TI - The efficiency of 1 M NH4Cl and 2 M NaCl for the isolation of pathogenic Nocardia from soil. AB - The present paper reports an improvement to the classical method of the paraffin bait, by the usage of 1 M NH4Cl or 2 M NaCl to eliminate contaminant microflora of soil. The purpose is to introduce a change in the paraffin bait method in order to reduce time required to isolate pathogenic strains of Nocardia from their natural sources. For this study three main criteria were used: a) Determination of the inhibitory effect of different concentrations of salts on soil microflora; b) The tolerance of Nocardia brasiliensis, Nocardia asteroides and Nocardia caviae (Nocardia otitidis caviarum) strains to these chemical inhibitors; c) Determination of the efficiency of salts in the isolation of Nocardia from soil when strains are grown on paraffin baits. PMID- 2594048 TI - Fusariosis in the shrimp Penaeus semisulcatus cultured in Israel. AB - The first case of a mycotic infection in shrimp in Israel is reported. Fusarium solani produced a large melanized lesion in a specimen of Penaeus semisulcatus cultured at Eilat, on the Red Sea. Fungal hyphae elicited a strong hemocytic response in cuticular and connective tissues. In the underlying muscle, the inflammatory reaction appeared weaker, suggesting a gradual failure by the host to resist mycelial invasion. Three cases of human keratomycosis by F. solani have been reported in recent years in Israel, suggesting that handling infected shrimp may represent a hazard to aquaculturists. PMID- 2594049 TI - Toxicity and toxin production by Fusarium isolates from New Zealand. AB - Sixty-two isolates of Fusarium were obtained from pasture grass and soil from various areas of New Zealand and identified as F. anthophilum, F. avenaceum, F. crookwellense, F. culmorum, F. graminearum, F. nivale, F. oxysporum, F. sambucinum, F. semitectum, F. tricinctum and an unidentified Fusarium spp. These isolates were grown on autoclaved rice and tested for toxicity to rats in feeding tests. Eighty two percent of the isolates were toxic, of which twenty-four percent were severely toxic and caused hemorrhages of stomach and intestine, hematuria, and finally death. Cultures of the most toxic isolates contained 0.1 to 104 ppm of deoxynivalenol, 0.7 and 7 ppm of 15- and 3-acetyldeoxynivalenol respectively, 0.2 to 4 ppm of fusarenon-X, 11 to 1021 ppm zearalenone, 40 to 272 ppm of the hemorrhagic factor (wortmannin), 2,100 to 7,200 ppm of moniliformin, 565 ppm of the cytotoxic factor (HM-8) and enniatin in substantial concentrations. F. sambucinum is reported as a moniliformin producer for the first time. PMID- 2594050 TI - Comparative study of four antifungal drugs in an experimental model of murine cryptococcosis. AB - A comparative study among amphotericin B, 5-fluorocytosine, itraconazole and fluconazole in the treatment of experimental cryptococcosis in mice, was carried out. Seventy male Balb C mice were inoculated intraperitoneally with 10(7) cells of Cryptococcus neoformans var. neoformans. They were divided in 7 groups of 10 animals each one: 1) treated with fluconazole by gavage at a daily dose of 16 mg/kg; 2) treated with itraconazole by gavage at a daily dose of 16 mg/kg; 3) treated with 5-fluorocytosine by gavage at a daily dose of 300 mg/kg; 4) treated with amphotericin B intraperitoneally at a dose of 6 mg/kg every other day; 5) control animals receiving polietilenglicol 200 by gavage; 6) control animals receiving distilled water by gavage and 7) control animals receiving sterile distilled water by intraperitoneal route. All the treatments started 5 days after the challenge inoculation and they were given for 2 weeks. The following parameters were taken into account: survival time, macroscopic aspect of the organ after the complete autopsy, microscopic investigation of yeasts in brain, lungs, spleen and liver, histopathology studies of these organs, the colony forming units per gram and massive seeding of brain and lungs. The survival index of the different groups was the most efficient method to measure the antifungal compounds activity. Amphotericin B increased significantly the animals survival and modified the histopathologic response in the studied organs. The colony forming units and the massive seeding in brain and lung showed that this antifungal agent is unable of producing the biological cure of this experimental model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2594052 TI - The need for information systems in the private sector. PMID- 2594053 TI - [14 days in the U.S.A]. PMID- 2594051 TI - Polyclonal B cell activation in paracoccidioidomycosis. Polyclonal activation in paracoccidioidomycosis. AB - Paracoccidioidomycosis (PCM) is often associated with hypergammaglobulinemia and increased serum levels of circulating immune complexes (CIC). In order to investigate whether polyclonal B lymphocyte activation (PBA) is a current process in PCM, we measured the numbers of IgG secreting cells (IgG SC) in the peripheral blood of 16 patients and of 8 healthy controls. The numbers of IgG SC were found to be significantly elevated in PCM patients. We also observed increased serum levels of IgG, IgA and CIC. These data reflect an activation of B lymphocytes in PCM patients. PMID- 2594054 TI - Raising the Titanic: solution for the problems in nursing education? PMID- 2594055 TI - The midwife and the surrogate childbearing family. PMID- 2594056 TI - Updating the management of the burned child. Part II. PMID- 2594057 TI - The Planned Parenthood Association of Southern Africa. PMID- 2594058 TI - Steps to deal with an outbreak of infection. PMID- 2594059 TI - AIDS escalation in Africa. PMID- 2594060 TI - Human genome initiative. Public debates on ethics. PMID- 2594061 TI - In vitro fertilisation. Reformation of advisory board urged. PMID- 2594062 TI - MHC protein structure. Getting into the groove. PMID- 2594063 TI - Daedalus: air of longevity. PMID- 2594065 TI - PCR origins. PMID- 2594064 TI - Pneumologists breathe easy. PMID- 2594066 TI - Similarity in membrane proteins. PMID- 2594068 TI - Limited receptor repertoire in a mycobacteria-reactive subset of gamma delta T lymphocytes. AB - The physiological role of lymphocytes bearing the gamma delta T-cell receptor (TCR) is still unclear. A function for a subset of these cells, however, is inferred from the finding that certain gamma delta chain-bearing lymphocytes are stimulated in a receptor-dependent fashion by mycobacterial antigens. We found that hybridomas derived from such cells in newborn murine thymus not only responded to mycobacterial purified protein derivative (PPD), but also exhibited an apparent autoreactivity. In neither response was haplotype-specific major histocompatibility (MHC) restriction demonstrable. To investigate the nature of antigen recognition by these gamma delta+ cells, we sequenced the gamma- and delta-chains from 28 PPD-reactive hybridomas, and found that a specific gamma chain, together with one of a limited set of delta-chains, was needed to generate the PPD specificity. The reactive gamma delta pairs exhibited considerable junctional diversity, which may act to produce differences in the fine specificities of the responding cells. PMID- 2594067 TI - Specificity pockets for the side chains of peptide antigens in HLA-Aw68. AB - We have determined the structure of a second human histocompatibility glycoprotein, HLA-Aw68, by X-ray crystallography and refined it to a resolution of 2.6 A. Overall, the structure is extremely similar to that of HLA-A2 (refs 1, 2; and M.A.S. et al., manuscript in preparation), although the 11 amino-acid substitutions at polymorphic residues in the antigen-binding cleft alter the detailed shape and electrostatic charge of that site. A prominent negatively charged pocket within the cleft extends underneath the alpha-helix of the alpha 1 domain, providing a potential subsite for recognizing a positively charged side chain or peptide N terminus. Uninterpreted electron density, presumably representing an unknown 'antigen(s)', which seems to be different from that seen in the HLA-A2 structure, occupies the cleft and extends into the negatively charged pocket in HLA-Aw68. The structures of HLA-Aw68 and HLA-A2 demonstrate how polymorphism creates and alters subsites (pockets) positioned to bind peptide side chains, thereby suggesting the structural basis for allelic specificity in foreign antigen binding. PMID- 2594069 TI - Forensic science: DNA fingerprinting on trial. PMID- 2594070 TI - Animal rights: German research fights back. PMID- 2594071 TI - EPO patient dispute: court battle ends at the start. PMID- 2594072 TI - Patent law: talking of harmony. PMID- 2594073 TI - AIDS: East Berlin risks grows. PMID- 2594074 TI - Journals and databanks. PMID- 2594075 TI - MS processing. PMID- 2594076 TI - Counting partners. PMID- 2594077 TI - Dangerous chemicals. PMID- 2594078 TI - Embryo research. PMID- 2594080 TI - Making authors toe the line. PMID- 2594079 TI - The overdose of drugs in Japan. AB - The Japanese consume enormous amounts of drugs on prescription, some of which are not legally available elsewhere in the world. The reason is a defective national system for drug approval and dispensing. PMID- 2594081 TI - Cell biology: mitosis and membranes. PMID- 2594082 TI - Immunology: making antigen-receptor genes. PMID- 2594083 TI - Bacterial zipper. PMID- 2594084 TI - Wavelength sensitivity in blindsight. AB - Blindsight--the residual visual functions observed in visualfield defects resulting from destruction of part of the primary visual cortex (striate cortex) even though visual stimuli presented in the field defect are not consciously perceived--has generated new insights into the nature of consciousness and the role of the extrastriate pathways in visual processing. Some patients can detect and localize unseen stimuli when they are required to guess. Discrimination of movement, flicker and orientation may also be present, but residual colour discrimination is controversial. Negative results imply that only the pathways from eye to striate cortex can transmit information about colour in primates. By measuring sensitivity to light of different wavelengths in patients with blindsight we show that spectral sensitivity in the blind fields is surprisingly high, with a reduction of only 1 log unit or less across the visible spectrum. It is also essentially normal in form, whether the patients are adapted to light or dark. The shift in peak sensitivity from medium to shorter wavelengths in adaptation to the dark (the Purkinje shift) and the presence of discontinuities in the light-adapted curve together show that blindsight involves both rod and cone contributions, and that some colour opponency remains. As colour opponency requires input from primate beta retinal ganglion cells, two-thirds of which degenerate transneurally after a striate cortical lesion in juvenile monkeys, our results show that the surviving subpopulation of primate beta cells is functional. PMID- 2594086 TI - Mechanism of antigen-driven selection in germinal centres. AB - The high affinity of antibodies produced during responses to T-cell-dependent antigens is associated with somatic mutation in the variable region of the immunoglobulin. Indirect evidence indicates that: (1) this arises by a process of hypermutation, acting selectively on rearranged immunoglobulin variable-region genes, which is activated in centroblasts within germinal centres; and (2) centrocytes, the progeny of centroblasts, undergo selection on the basis of their ability to receive a positive signal from antigen. We have now performed experiments analysing this selection process, and found that, on culture, centrocytes isolated from human tonsil kill themselves within a few hours by apoptosis. This is not a feature of other tonsillar B cells. Centrocytes can be prevented from entering apoptosis if they are activated both through their receptors for antigen and a surface glycoprotein recognized by CD40 antibodies. PMID- 2594085 TI - Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor. AB - Ciliary neurotrophic factor (CNTF) was originally characterized as a survival factor for chick ciliary neurons in vitro. More recently, it was shown to promote the survival of a variety of other neuronal cell types and to affect the differentiation of E7 chick sympathetic neurons by inhibiting their proliferation and by inducing the expression of vasoactive intestinal peptide immunoreactivity (VIP-IR). In cultures of dissociated sympathetic neurons from newborn rats, CNTF induces cholinergic differentiation as shown by increased levels of choline acetyltransferase (ChAT). This increase is paralleled by a reduction of tyrosine hydroxylase (TH) activity. Moreover, CNTF promotes the differentiation of bipotential 02A progenitor cells to type-2-astrocytes in vitro. To help establish which, if any, of these functions CNTF exerts in vivo, it is necessary to determine its primary structure, cellular expression, developmental regulation and localization. The complementary DNA-deduced amino-acid sequence and subsequent expression of cDNA clones covering the entire coding region in HeLa cells indicate that CNTF is a cytosolic protein. This, together with its regional distribution and its developmental expression, show that CNTF is not a target derived neurotrophic factor. CNTF thus seems to exhibit neurotrophic and differentiation properties only after becoming available either by cellular lesion or by an unknown release mechanism. PMID- 2594087 TI - Genetic evidence that ZFY is not the testis-determining factor. AB - In mammals, the testis determining gene (TDF), present on the Y chromosome, induces the undifferentiated gonads to form testes. The position of TDF on the human Y chromosome has been defined by analysing the genomes of XX males and XY females, generated by abnormal genetic exchange between the X and Y chromosomes in male meiosis. In this way TDF has been localized close to the pseudoautosomal region shared by the sex chromosomes, in the distal Y-specific region. A recently cloned human gene, ZFY, has many features indicating that it is TDF. For example, ZFY encodes a protein with many features of a transcription factor including a domain with multiple 'zinc-finger' motifs. Less consistent with ZFY being TDF, however, is the presence of a very similar gene, ZFX, on the X chromosome, and the presence of a sequence related to ZFY on autosomes in marsupials. We now report on analysis of XX males lacking ZFY. In these individuals, the male phenotype could be explained by a mutation in a gene 'downstream' of ZFY in the sex-determining hierarchy; but in that case there should be no exchange of material between the X and Y chromosomes. We find on the contrary that in 4 XX males lacking ZFY, there is exchange of Y-specific sequences next to the pseudoautosomal boundary, redefining the region in which TDF must lie. PMID- 2594088 TI - A highly divergent HIV-2-related isolate. AB - It has been suggested that the human immunodeficiency virus type 2 (HIV-2) and the simian immunodeficiency virus from rhesus macaques (SIVmac) evolved from the sooty mangabey virus SIVsm (ref. 1). We now describe an HIV-2-related isolate, HIV-2-D205, from a healthy Ghanaian woman that is genetically equidistant to the prototypic HIV-2 strains and to SIVsm and SIVmac. Supported by the observation that HIV-2D205 differs in a step of envelope glycoprotein processing, our data indicate that it could represent an alternative HIV-2 subtype and that viruses of the HIV-2/SIVsm/SIVmac group could have already infected humans before HIV-2 and SIVsm/SIVmac diverged. PMID- 2594089 TI - Isolation and characterization of the G-actin-myosin head complex. AB - The two main proteins involved in muscular contraction and cell motility, myosin and actin, possess the intrinsic property of being able to form filamentous structures. This property poses a serious impediment to the study of their structures and interactions, and a considerable effort has thus been made to isolate their functional domains. The globular part of myosin, subfragment-1 (S1), which possesses ATPase and actin-binding sites as well as supporting the movement of actin filaments during in vitro assays, has been isolated. But because S1 is efficient in inducing actin polymerization, as is myosin, it has not been possible to prepare and characterize a complex of S1 with monomeric actin (G-actin). We have now used chromatographically purified proteins to show that only the S1 isoenzyme carrying the A1 light-chain subunit promotes actin polymerization. The other isoenzyme, S1 (A2), carrying the A2 light-chain subunit, binds to actin, forming a tight complex of G-actin and S1 in a 1:1 ratio. This new functional difference between myosin isoforms directly implicates the A1 light-chain in myosin-induced actin polymerization. Additionally, this finding should lead to the purification of the stable G-actin-S1 complex needed to resolve the structure and to understand the molecular dynamics of the actin myosin system. PMID- 2594091 TI - Deutsche Gesellschaft fur Pharmakologie und Toxikologie. Abstracts of the fall meeting. 18-21 September 1989, Koln. PMID- 2594090 TI - Style self-incompatibility gene products of Nicotiana alata are ribonucleases. AB - Self-incompatibility in flowering plants is often controlled by a single nuclear gene (the S-gene) having several alleles. This gene prevents fertilization by self-pollen or by pollen bearing either of the two S-alleles expressed in the style. Sequence analysis shows that three alleles of the S gene of Nicotiana alata encode style glycoproteins with regions of defined homology. Two of the homologous regions also show precise homology with ribonucleases T2 (ref. 4) and Rh (ref. 5). We report here that glycoproteins corresponding to the S1, S2, S3, S6 and S7 alleles isolated from style extracts of N. alata are ribonucleases. These style S-gene-encoded glycoproteins account for most of the ribonuclease activity recovered from style extracts. The ribonuclease specific activity of style extracts of the self-incompatible species N. alata is 100-1,000-fold higher than that of the related self-compatible species N. tabacum. These observations implicate ribonuclease activity in the mechanism of gametophytic self incompatibility. PMID- 2594092 TI - Cysticercosis: pandemonium in pigdom. PMID- 2594093 TI - A rare cause of intra-abdominal hemorrhage. Leiomyoma of the small bowel. AB - As a result of infrequent occurrence, small bowel tumors of the intestine offer a diagnostic challenge. A spectrum of presentations are possible, ranging from vague abdominal symptoms to life-threatening intra-abdominal hemorrhage. Contrast radiographs are helpful in diagnosis but additional studies may be necessary. Treatment is usually simple excision. The prognosis of benign tumors is excellent. Because of the non-specificity of signs and symptoms of small bowel tumors, a high index of suspicion is required, especially since these lesions themselves can be dangerous and often occur in the age group for intra-abdominal malignancy. PMID- 2594094 TI - The multidisciplinary approach to adenocarcinoma of the prostate at Moore Regional Hospital. PMID- 2594096 TI - The many expressions of Sweet Thing. PMID- 2594095 TI - Sexually transmitted diseases. PMID- 2594097 TI - CHD, MI, & I. The story of a 57-year love-hate relationship. PMID- 2594098 TI - Death with dignity. PMID- 2594099 TI - Expert medical witnesses. PMID- 2594100 TI - The resource based relative value scale. PMID- 2594102 TI - Medical ethics: on Dr. Davant's article and Dr. Alexander's comment. PMID- 2594103 TI - Meeting OSHA hazard communication standards. PMID- 2594101 TI - Abortion. PMID- 2594104 TI - Hypertension and renal disease among minorities. Genetic defect may increase susceptibility in blacks. PMID- 2594105 TI - Identifying and treating hypertension in the black and Hispanic population. PMID- 2594106 TI - A break-even point in the ESRD program. PMID- 2594107 TI - ESRD centers deserve a level playing field... PMID- 2594108 TI - Squeezing the inner-city dialysis dollar. PMID- 2594109 TI - More research funding needed to improve transplant success rates. PMID- 2594110 TI - Quality of life and the "business" of nephrology. PMID- 2594111 TI - [Number of operations and mortality in surgery of the heart and large intrathoracic vessels]. PMID- 2594112 TI - [Predictive characteristics for early mortality in patients on the waiting list for aortocoronary bypass surgery]. AB - In 1986, 1124 patients were selected for coronary artery bypass surgery (CABG). Of patients in line for CABG 25 (2.2%) died of a cardiac cause before operation. This complies with a cardiac mortality risk of 8.3 patients per 100 patient years follow-up. To assess patient characteristics predictive for early mortality before surgery, 25 deceased patients were analysed and compared with 50 controls matched by age, gender, type of surgery and priority. Using multivariate analysis, cardiac enlargement on chest X-ray, positive exercise testing with short duration (less than 6 minutes), smoking, coumarin treatment, unstable angina just prior to angiography and left main or three-vessel disease were independent predictors for death while waiting for CABG. We conclude that patients with the above mentioned characteristics have an increased short term mortality while waiting for CABG. These indicators may contribute important information for determination of priority in patients at high risk while waiting for CABG. PMID- 2594113 TI - [Frequency and surgical mortality in surgery of the heart and intrathoracic large vessels. II. Operations other than direct coronary revascularization]. AB - Just as bypass operations, the number of operations for other lesions of the heart and great vessels are increasing. The surgical mortality among infants operated on because of congenital anomalies is high. Despite the rising number of patients in this age group, mortality after surgery for ductus arteriosus and for Fallot's tetralogy is falling. The mortality of certain operations for non congenital anomalies also shows a tendency to decrease. Hitherto, the mortality rate of cardiac transplantations has been relatively low. Progress of cardiac surgery appears to manifest itself with a decreasing nationwide number of deaths from congenital anomalies of the heart and great vessels. PMID- 2594114 TI - [Attacks of muscle weakness; a diagnostic problem?]. AB - A girl with periodic weakness since the age of two, is presented. Not until four years after the first symptoms appeared hypokalaemic periodic paralysis was diagnosed. Some aspects of this disease are discussed. PMID- 2594115 TI - [Peer review]. PMID- 2594116 TI - [Headache like a thunderclap in a clear sky: subarachnoid hemorrhage or an innocent disorder?]. PMID- 2594117 TI - [Reconstruction of the bladder from ileum following cystectomy]. PMID- 2594118 TI - [Eurothemes. Pay according to work: irritations and irritating developments]. PMID- 2594119 TI - [Obstructive sleep apnea in childhood]. PMID- 2594120 TI - [Calcium content of food and prevention of postmenopausal osteoporosis]. PMID- 2594121 TI - [Vitamin d prophylaxis for 2 age groups]. PMID- 2594122 TI - [The probability of survival of patients with bronchial carcinoma]. AB - A study was made of the effect of the discontinuation of population screening for tuberculosis, on January 1, 1982, on the referral pattern and therapeutic results in patients with bronchial carcinoma. In 1981 only a few patients were referred because of lesions detected at the screening. Accordingly, discontinuing the screening had no demonstrable effect. Also, there was no difference between patients referred because of a fortuitous finding and those who consulted because of symptoms. Nevertheless the results, especially the 5-year survival rates, were far better for those whose tumours had favourable TNM classifications. This applied in particular if resection of parts of the lung was feasible and operation revealed no metastases in mediastinal lymph nodes and no infiltrating growth. For this group of patients the 5-year survival rate amounted to 59.4%. With only symptomatic treatment the rate was 16.7% and for patients with small cell anaplastic carcinomas given chemotherapy, it was 5.6%. PMID- 2594123 TI - [Analysis of the surgical treatment of pancreas head and peri-ampullary carcinoma in 236 patients]. AB - Between 1978 and 1987, 236 patients were admitted for cancer in the pancreas or periampullary region. In 93 patients a resection of curative intent was performed, while 88 patients underwent a palliative procedure and 55 patients no operation. The operative mortality was 9%. In the complete group of patients, age above 70 years and preoperative jaundice were of prognostic significance. A tumour size greater than 3.5 cm after resection implies a better prognosis than tumours less than 3.5 cm. The 1-, 3- and 5-year survival rates of the resected patients with pancreatic head cancer were 59%, 12% and 8% respectively, those of patients with periampullary cancer 90%, 49% and 30% respectively. After a palliative procedure or only a laparotomy survival was significantly lower (p less than 0.001), with 1-year survival of 16% and 2-year survival of 4%. After resection of curative intent for cancer of the head of the pancreas 21 cases still had microscopical remnants of tumour (T3, N1b). Survival of these patients was not significantly different from that of patients with a curative resection. Surgical resection for cancer of the head of the pancreas has to be considered as a mainly palliative treatment, but given low operative mortality (less than 10%) it is still the treatment of choice to gain longer survival and in some cases definitive cure. PMID- 2594124 TI - [Neuropsychological findings in children with Gilles de la Tourette syndrome]. AB - Eight children with the syndrome of Gilles de la Tourette underwent a neuropsychological assessment. The results were compared with those of eight children with proven lesions of the right cerebral hemisphere and with eight children with learning disabilities without neurological disturbances. Our findings do not support organicity or dysfunctions of the right hemisphere in children with Gilles de la Tourette syndrome. PMID- 2594125 TI - [Q-fever as a cause of myocarditis in childhood]. AB - Q-fever occurs in The Netherlands in childhood more often than used to be believed. We treated an 8-month-old infant with congestive myocarditis associated with a seroconversion against Coxiella burnetii. The infection was probably caused by the father, who a few weeks earlier had visited his native Surinam, where he frequently was surrounded by domestic animals and drank raw cow's milk. After 2.5 years the child's general and cardial conditions are good although digoxin therapy is still necessary. PMID- 2594126 TI - [Who pays attention to the prostate?]. PMID- 2594127 TI - [The EEG in neurological practice; shifts in the diagnosis]. PMID- 2594128 TI - [Finally action against passive smoking]. PMID- 2594129 TI - [Extension of life through cytostatic treatment]. PMID- 2594130 TI - Experimental intracranial hypertension following cisternal injection of various blood components. AB - Intracranial pressure (ICP) was recorded in 30 dogs which underwent cisternal injection of blood, serum, red blood cells (RBC). RBC ghosts, oxyhemoglobin or bilirubin. The amount of injection was 8-10 ml of blood or an equivalent volume of blood components. Blood or RBC showed a sustained ICP of 15 to 25 mmHg, and RBC ghosts caused a slight transient rise of ICP. In contrast, oxyhemoglobin or bilirubin induced marked intracranial hypertension up to 60-80 mmHg which was associated with frequent pressure waves. Histological examination disclosed aseptic meningitis at the base of the brain and inflammatory changes in the floor of the fourth ventricle after the injection of oxyhemoglobin or bilirubin. It is suggested that the breakdown products of RBC might be causative factors of the intracranial hypertension following subarachnoid hemorrhage. PMID- 2594131 TI - Liberation of eosinophil granules in the inner capsule of chronic subdural hematomas. AB - The role of eosinophilic infiltration in the inner capsule was studied in 35 consecutive cases of chronic subdural hematomas. The eosinophilic infiltration in the inner capsule was microscopically observed in 10 of the 22 cases which were associated with the infiltration in the outer capsule. The majority of eosinophils were ultrastructurally fully granulated and contained numerous glycogen granules. In contrast, some eosinophils were undergoing marked cellular disruption or necrosis with a resultant liberation of secretion granules. This was confirmed in all of the 10 cases. The free granules were closely apposed to fibrin strands which were interwoven with a number of disintegrating inflammatory cells. The inner capsule was usually adhered by massive fibrinous clot and the remaining liquified hematoma contained low levels of fibrinogen and high levels of FDP. Secretion granules of the eosinophils were previously demonstrated to contain plasminogen or cytotoxic material. Accordingly, the eosinophils conceivably contribute to both the fluidity of subdural clot and the disruption of inflammatory cells in chronic subdural hematomas. PMID- 2594132 TI - [Lumbar disk hernia: microsurgery--yes or no?]. AB - Microsurgery has been performed in about three-quarters of 5,000 patients operated on since 1973 for herniation of a lumbar disc. The findings obtained in two groups of patients who had undergone primary surgery, in the one group by classical methods, in the other by microsurgery, are compared. The two groups were similar in respect of age and sex distribution, localisation of the discal hernia, duration of signs and symptoms and follow-up time. Results classified "very good" were seen more often in the microsurgery group, where no improvement or postoperative aggravation of the signs was relatively rare. The difference compared with the group treated by conventional surgery was mainly in respect of appearance of a postoperative vertebral syndrome, and not so much with regard to the radicular pain syndrome and radicular motor deficits. Unlike some other researchers, we found no difference between the two groups in respect of frequency of local reoperation or of spondylodiscitis. In patients whose disc hernia is mainly of a soft consistency, unilateral and at a single level only, microsurgery requires a shorter access, involves less damage to tissues, allows a better haemostasis and good surgical visualisation. The operation is minimally invasive, the area involved more or less extensive depending on the individual pathology. Magnification under good lighting is indicated in all cases. PMID- 2594133 TI - Intraventricular or epidural injection of morphine for severe pain. AB - Intraventricular or epidural injection of morphine through implantable infusion devices was used for severe pain in 50 patients with advanced cancer, arachnoiditis, or spinal injury. Intraventricular catheter was inserted for injection of morphine in 21 patients, 29 were treated through epidural infusion. For the evaluation of results the multimodal evoked potential (MEP) has been obtained before and after each treatment. 80% of the patients experienced good results. No significant side effects have been noted in patients with either epidural or intraventricular injection of morphine. These may be excellent methods for pain control in well selected patients. PMID- 2594134 TI - [Diagnosis of hypophyseal abscess using MRI and high resolution CT]. AB - Preoperative diagnosis of pituitary abscess is very difficult. In particular, differentiation from other cystic processes of the sellar region is delicate. The clinical and radiological findings of a case of pituitary abscess are presented. Since CT and MRI are of major importance for routine pituitary screening, the aspects of these methods are emphasized. In our experience, both methods can contribute to preoperative diagnosis. PMID- 2594135 TI - [Plasmacytoma involving the atlas and axis]. AB - Report on a rare localisation of a plasmocytoma in the upper part of the cervical spinal cord. PMID- 2594136 TI - Malignant schwannoma of brachial plexus presenting as spinal cord compression. AB - A 40-year-old male presented clinically with features of C6 radiculomyelopathy. An intradural extramedullary malignant schwannoma was removed at laminectomy. Foraminal extension of the tumour could not be removed in spite of foraminotomy, and no root attachment was found. Frequent intraspinal recurrences were treated with local resection. Delayed appearance of a supraclavicular mass, CT scan and exploration of supraclavicular fossa disclosed its origin from the upper trunk of brachial plexus. PMID- 2594137 TI - Aneurysmal bone cyst associated with fibrous dysplasia of the skull. AB - A 25 year old patient presented with a post-traumatic soft tissue swelling of the occiput, overlying an area of bone expansion and destruction. At operation an aneurysmal bone cyst was found. 11 years previously a similar parietal lesion had been found in conjunction with fibrous dysplasia. The differential diagnosis and treatment of this entity is discussed. PMID- 2594138 TI - Intra-extracranial thrombosis of the internal carotid artery associated with meningioma. AB - Cases of internal carotid artery occlusion associated with an intracranial tumor are rare. The authors report two cases of complete occlusion of the internal carotid artery. In one case the thrombosis was probably caused by direct compression of the carotid siphon by a large meningioma arising from the inner third of the sphenoid wing. In the other it was associated with multiple meningiomatosis although there was no contiguity between the intracranial tumors and the occluded carotid artery. After a review of literature we think they are of some interest, and we have found an interesting incidence of association between thrombosis and meningioma. PMID- 2594139 TI - Effects of antidepressant drugs on inositol phospholipid hydrolysis in rat cerebral cortical slices. AB - The effects of several different types of antidepressant drugs on phosphoinositide hydrolysis by slices of rat cerebral cortex was investigated by prelabeling inositol phospholipids with [3H]inositol and then measuring the formation of [3H]inositol phosphates (a total fraction consisting of the mono- and poly-phosphates was collected) in the presence of 10 mM LiCl. All of the drugs tested (amitriptyline, trimipramine, mianserin, desipramine, tranylcypromine, and citalopram) inhibited NE-stimulated [3H]inositol phosphate formation. This inhibition appeared to be due to antagonism of alpha 1-receptors. In addition to inhibiting the effects of NE, the tricyclic antidepressants themselves were able to stimulate [3H]inositol phosphate formation. This stimulation occurred at drug concentrations higher than that needed to inhibit stimulation by NE. Stimulatory effects of the antidepressants themselves were not blocked by the alpha 1-antagonist, prazosin. An examination of the types of inositol phosphates formed revealed that formation of inositol monophosphate was stimulated, but that inositol biphosphate production was decreased by tricyclic antidepressants compared to control. PMID- 2594140 TI - Metal cations as synaptosomal calcium blockers in studies with Fura-2. AB - Metal ions are often used to block calcium channels in various tissues, including synaptosomes. In the present study, Fura-2 was used to determine the effectiveness of various metal ions as calcium channel blockers in rat brain synaptosomes in vitro. In buffer solutions, La3+ and Cd2+ increased the Fura-2 fluorescence in a manner similar to Ca2+. Ni2+ and Mn2+ appeared to be fluorescence quenching cations, and Sr2+ and Co2+ had little effect on the fluorescence of Fura-2. In suspensions of synaptosomes under resting conditions, Cd2+, Ni2+ and Mn2+ were found to be not suitable for use in synaptosome studies. On the other hand, La3+ and Co2+ had little effect on the Fura-2 fluorescence of resting synaptosomes, and under depolarizing conditions, La3+ and Co2+ decreased the Fura-2 fluorescence. These results, therefore, suggest that La3+ and Co2+ may be suitable as calcium channel blockers in synaptosome studies. PMID- 2594141 TI - Effect of partial ischemia on phospholipids and postischemic lipid peroxidation in rabbit spinal cord. AB - Rabbit spinal cord, subjected to severe partial ischemia induced by abdominal aorta ligation tightly below the renal arteries, was analyzed for phospholipid composition and levels of lipid peroxidation products after 10, 20, and 40 min of the insult. Under conditions when spinal cord blood flow was decreased below 5% of control, concentrations of inositol and ethanolamine phospholipids were decreased by 30% and 10%, respectively. Phosphatidic acid concentration was also altered during ischemia. No accumulation of thiobarbituric acid reactive substances (TBA-RS), conjugated dienes and fluorescent lipid soluble material was found throughout the ischemic period. Pattern of TBA-RS, conjugated diene, and fluorophore formation during postischemic in vitro incubation without and with a peroxidation couple (Fe2+, ascorbic acid) showed increased susceptibility to postischemic lipid peroxidation in tissues after 20 and 40 min of ischemia. PMID- 2594142 TI - Regional distribution of potassium, calcium, and six trace elements in normal human brain. AB - Eight elements (i.e. K, Ca, Mn, Fe, Cu, Zn, Se, and Rb) were measured in 50 different regions of 12 normal human brains by particle-induced X-ray emission (PIXE) analysis. The dry weight concentrations of K, Fe, Cu, Zn, Se, and Rb were consistently higher for gray than for white matter areas. The K, Zn and Se concentrations for the regions of mixed composition and, to some extent, also the Rb concentrations, were intermediate between the gray and white matter values, and they tended to decrease with decreasing neuron density. The mean dry weight concentrations of K, Ca, Zn, Se, and Rb in the various brain regions were highly correlated with the mean wet-to-dry weight ratios of these regions. For Mn, Fe, and Cu, however, such a correlation was not observed, and these elements exhibited elevated levels in several structures of the basal ganglia. For K, Fe, and Se the concentrations seemed to change with age. A hierarchical cluster analysis indicated that the structures clustered into two large groups, one comprising gray and mixed matter regions, the other white and mixed matter areas. Brain structures involved in the same physiological function or morphologically similar regions often conglomerated in a single subcluster. PMID- 2594143 TI - Endogenous homovanillic acid levels differ between rat and rabbit caudate, hippocampus, and cortical regions. AB - Endogenous dopamine (DA) levels and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3MT) and homovanillic acid (HVA) were measured by high-performance liquid chromatography in the entorhinal-piriform (EnPi), cingulate (CIN), sensorimotor (SSM) and visual (VIS) cortices as well as is the caudate (CAU) and hippocampus (HIP) of Sprague-Dawley (SD) rats and New Zealand (NZ) rabbits. The DA, DOPAC and 3MT contents were similar in both species. The HVA levels however, although they followed DA distribution, were several-fold higher in NZ rabbits than in SD rats for all cortices, HIP and CAU. In addition, total metabolite contents and DA turnover (estimated from 'DA metabolite/DA' ratios) were significantly higher in NZ rabbits than in SD rats, suggesting an increased release and/or metabolism in the former species. The HVA/DA ratios were much higher for NZ rabbit regions than for SD rats, indicating an increased DA release in the former species since the DOPAC/DA ratios (index of intraneuronal degradation) were similar. PMID- 2594144 TI - In vitro insertion of the myelin proteolipid apoprotein into oligodendrocyte plasma membranes. AB - Uncoated vesicles (UCV) loaded with the myelin proteolipid apoprotein covalently tagged with fluorescein (PLPF) were found to interact with isolated oligodendrocytes from bovine brain at 4 degrees C as well as at 37 degrees C. After 1.5 hours of incubation, the labeled protein was localized in the cell membranes. After 2.5 hours the fluorescence intensity associated with the oligodendrocytes decreased and completely disappeared at t = 3.5 hours. Addition of KCl or EDTA in the incubation medium significantly hindered the interaction with cells. In contrast, the elimination of membrane proteins from UCV did not perturb cell labeling. A specific role of PLP was suggested since UCV loaded with a soluble protein (BSAF) led to a weak cell labeling. PMID- 2594146 TI - In vivo rates of protein synthesis in brain, muscle, and liver of five vertebrate species. AB - To compare cerebral protein metabolism rates in vivo, protein synthesis rates of three organs of five vertebrate species were measured after a single i.p. injection of a flooding dose of [1-14C]valine. In muscle, brain, and liver, the respective average protein synthesis rates, expressed as percent of total protein bound valine replaced per hour, that is, percent synthesis per hour, in goldfish at 22 degrees C body temperature, were 0.07, 0.23, and 0.57%; in the bullfrog at 20 degrees C, 0.06, 0.18, and 0.55%; in the white Leghorn chicken at 39 degrees C, 0.24, 0.70, and 2.17%; and in the mouse at 38 degrees C, 0.22, 0.65, and 2.0%. In the Tokay lizard at different body temperatures, the synthesis rates were 0.04, 0.13, and 0.43% at 26 degrees C; 0.05, 0.20, and 0.63% at 32 degrees C; and 0.07, 0.27, and 0.81% at 38 degrees C. The results demonstrate differences in protein synthesis rates in organs of the various species examined. The differences among the species seem to be due, to a major extent, to differences in body temperature; rates in lizard are below those in other species at temperatures tried. Protein synthesis rates in brain in all species are almost three times lower than those in liver and almost three times higher than those in muscle. PMID- 2594145 TI - Queuine is incorporated into brain transfer RNA. AB - Pig brain tRNA was assayed for the presence of queuosine in the first position of the anticodon for each of the Q-family of tRNAs (aspartyl, asparaginyl, histidyl and tyrosyl). The brain tRNA was aminoacylated with each of the four amino acids and the aminoacylated tRNA's analyzed by RPC-5 chromatography. The results of this study show that for all four tRNAs of the family, queuine is substituted for guanine in virtually 100% of the anticodons. Therefore, it can be concluded that queuine is able to cross the blood-brain barrier and that brain contains guanine queuine tRNA transglycosylase, the enzyme responsible for the excision of guanine from the original transcripts of these tRNAs and insertion of queuine. The determination of whether the tRNA contained queuine was made from the elution profile of the RPC-5 chromatograms and the results confirmed by a change in the RPC-5 elution profile when the tRNAs were reacted with BrCN or NaIO4. PMID- 2594148 TI - Chronic lithium treatment and status epilepticus induced by lithium and pilocarpine cause selective changes of amino acid concentrations in rat brain regions. AB - We measured the effects of four weeks of dietary lithium treatment and of status epilepticus induced by administration of pilocarpine to lithium-treated rats on the concentrations of amino acids in four regions of rat brain: cerebral cortex, hippocampus, striatum, and substantia nigra. To ensure accurate quantitation of the amino acids, animals were sacrificed by focussed beam microwave irradiation and amino acids were measured using a fully validated triple-column ion-exchanged amino acid analyzer with post-column o-phthalaldehyde derivatization and fluorometric detection. The concentrations of four amino acids, threonine, methionine, lysine and tyrosine, were increased significantly in two to four brain regions by chronic lithium treatment. Their concentrations remained elevated, or were further increased, during status epilepticus. The concentrations of eight amino acids and ammonia were not altered by lithium treatment but increased in concentration during status epilepticus in some brain regions. Glycine, serine, arginine and citrulline were decreased by chronic lithium treatment. Status epilepticus increased the concentrations of these four amino acids above that found in the lithium-treated samples in some of the brain regions that were examined. Six amino acids and glutathione were generally unaltered by both treatments. These results are related to the effects of lithium treatment and are compared with changes reported by others following treatment with a variety of convulsive stimuli. PMID- 2594147 TI - The influence of ovarian hormones on the rat oviductal and uterine concentration of noradrenaline and 5-hydroxytryptamine. AB - This paper describes the effects of estradiol and progesterone on the concentrations of noradrenaline and 5-hydroxytryptamine in the Wistar rat oviduct and uterus. The levels of noradrenaline and 5-hydroxytryptamine are higher in the oviduct than in the uterus whereas p-tyrosine and tryptophan are similar in both tissues. Estradiol treatment reduced the oviductal concentration of noradrenaline but not 5-hydroxytryptamine in oviduct, while the concentrations of both noradrenaline and 5-hydroxytryptamine were reduced in uterine horn. The levels of noradrenaline in the oviduct and uterus in rats in estrus were lower than those of diestrous rats. Bilateral ovariectomy produced an increase in uterine noradrenaline and 5-hydroxytryptamine levels. These changes were reversed in the presence of ovarian hormone as indicated by experiments where unilateral ovariectomy was performed. Reserpine administration reduced noradrenaline concentration in both the oviduct and the uterus but did not change oviductal or uterine 5-hydroxytryptamine. These results indicate the existence of noradrenaline within postganglionic sympathetic nerve terminals and suggest that estrogens increase the utilization and the synthesis of noradrenaline in both the oviducts and the uterine horns. With respect to 5-hydroxytryptamine the data support the concept that it is mainly associated with mast cells. PMID- 2594149 TI - Changes of amino acid gradients in brain tissues induced by microwave irradiation and other means. AB - Focused microwave irradiation to the head (FMI) has been used extensively by neurochemists for rapid inactivation of enzymatic activity in brain tissues and the preservation, for in vitro analysis, of in vivo substrate concentrations. Periodically the suitability of this technique for regional studies has been questioned. Evidence has now been obtained, on the basis of altered concentration gradients for GABA and taurine from the Substantia Nigra (SN) to an Adjacent Dorsal Area (ADJ), that FMI not only inactivates enzymes, but also facilitates rapid diffusion of small molecules from areas of high concentrations to adjacent areas of lower concentration. To a lesser extent, the implantation of plastic injection cannulas also decreased these concentration gradients. These results offer clear evidence that FMI is ill suited and unreliable for studies designed to map and compare the "in vivo" regional concentrations of diffusible organic molecules (such as amino acids) in brain tissues. Any invasive technique that compromises membrane barriers is likely to produce smaller similar effects. PMID- 2594150 TI - [Analysis of regional blood flow, blood volume, oxygen and glucose metabolism in heterogeneous parts of untreated high grade gliomas using positron emission tomography (PET)]. AB - A high resolution positron emission tomography (PET), HEADTOME III, has enabled us to visualize heterogeneous parts, i.e. viable, necrotic, and edematous portions in malignant gliomas, and to quantify regional hemocirculation and metabolism of the tumors using 15O and 18F-fluorodeoxyglucose tracers. Hemocirculatory and metabolic indices of regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen consumption (rCMRO2) and glucose consumption (rCMRGl) were studied in eight patients with untreated malignant gliomas. Regions of interest (ROIs) in PET images were focused on lesions corresponding to contrast enhancing areas, central low density areas of the tumors, and peritumoral low density areas in CT scans. In the viable portion of the gliomas, rCBV (5.20 +/- 1.18ml/100ml, mean +/- SD, n = 8) was significantly higher than that of the contralateral gray matter (p less than 0.05), which is suggestive of high vascularity; rOEF (0.36 +/- 0.16) and rCMRO2 (1.66 +/- 0.45ml/100ml/min) values markedly decreased (p less than 0.05, p less than 0.01). On the other hand, rCBF (36.3 +/- 13.0ml/100ml/min) and rCMRGl (5.94 +/- 1.15mg/100ml/min) were similar to that of the contralateral gray matter. A relative dissociation between oxygen and glucose metabolism indicates anaerobic glycolysis in the energy metabolism of malignant gliomas. In the central low density area, rCBF, rCBV, rOEF, rCMRO2, rCMRGl values decreased significantly from the viable portion and the contralateral gray matter. rOEF was markedly reduced in the central low density area as compared with that of the peritumoral low density area. The rOEF reduction indicates that oxygen metabolism of gliomas is the first to fail, accompanied by autoregulatory impairment of vessels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2594151 TI - [Cerebral hemodynamics and functional prognosis in hydrocephalus]. AB - The functional outcome of cerebral hemodynamics in the chronic stage of juvenile hydrocephalus was determined using single photon emission computed tomography (SPECT). Five patients including three with aqueductal stenosis, one with post meningitic hydrocephalus, and one case with hydrocephalus having developed after repair of a huge occipital encephalocele. Early images of cerebral blood flow (CBF) were obtained 25 minutes after intravenous injection of 123-I Iodoamphetamine (IMP), and late images were scanned 3 hours later. Cerebral blood volume (CBV) was also measured using 99mTc in three patients. Twenty cases with adult communicating hydrocephalus were also investigated from the point of view of shunt effectiveness. Although there was no remarkable change in the cerebrovascular bed in the juvenile cases, CBF of the remnant brain parenchyma was good irrespective of the degree of ventricular dilatation. There was a periventricular-reduced IMP uptake in each case, however it somehow matched the ventricular span. Functional outcome one to 23 years after the initial shunt operation was good in every case, despite multiple shunt revisions. Redistribution on late images had no bearing on clinical states. In adult cases, 8 patients with effective shunting demonstrated a relatively localized periventricular low perfusion, with preoperative increased cerebrospinal fluid (CSF) pressure. On the contrary, 12 patients with no improvement with or without shunting showed disproportionately widespread periventricular-reduced IMP uptake, despite low CSF pressure. The present study indicates that periventricular hemodynamics may play an important role in cerebral function compromised by hydrocephalus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2594152 TI - [Split rib cranioplasty]. AB - Presented are an operative technique and clinical indications for split rib cranioplasty, and the results of its practical application. This technique was applied to 6 patients, in five of whom infection after previous cranioplasty had been noted before split rib cranioplasty. Two patients out of the 5 had been suffering from inveterate and repetitive postoperative infections; one patient had been operated on twice and the other three times, respectively. Operative results were excellent without serious and/or infectious complications, except initially in one patient who presented hemothorax after rib harvest. This method can be applied for those who have extensive defect of the skull or who need additional reconstruction using split rib graft because of infectious complications after previously performed cranioplasty. This technique also has the following advantage; cranial contour is easy to reconstruct and good cosmetic results can be expected. PMID- 2594153 TI - [Primary intracranial T cell type malignant lymphoma: a case report]. AB - Primary intracranial T cell type malignant lymphoma is extremely rare. Only 8 cases are reported in the literature so far. In this paper, a case with this type of malignant lymphoma is reported. A 41-year-old man was admitted because of abnormal behavior. Enhanced CT scan demonstrated high density mass and perifocal low-density area in the right frontal lobe, the right basal ganglia and the periventricular region. Specimen biopsied from right frontal lobe was submitted for histological examination. An immunohistochemical technique using monoclonal surface markers confirmed reactivity for LCA, MT-1, OKT-4 and OKT-8, while there was no reactivity for MB-1 and OKB-2. Pathological diagnosis was diffuse medium T cell type malignant lymphoma. Postoperatively, after 60 Gy irradiation, the tumor disappeared. There is no difference on CT findings between B cell type and T cell type malignant lymphoma. PMID- 2594154 TI - [Blunt injury of the vertebral artery: report of three cases]. AB - The authors reported three cases, whose vertebral arteries had been injured by blunt trauma to the neck which was followed by cerebello-brainstem infarctions. Case 1: a 32-year-old man, who developed severe vertigo and nausea 7 days after a traffic accident. He showed neck pain and horizontal nystagmus on admission. Three days later, he became drowsy. CT scan of the head demonstrated right-side cerebellar infarction, and the angiography revealed an occlusion of the right vertebral artery at C4-5 level. After the removal of the right cerebellar hemisphere, he recovered neurologically and was discharged from the hospital, able to walk. Case 2: a 47-year-old man, who suddenly became comatose 6 hours after an accident. Plain CT demonstrated a highly dense basilar artery. Angiography revealed the occlusion of the left vertebral artery, and severe stenosis of the right vertebral artery. The basilar artery was not visualized. Anticoagulant therapy was started immediately. He survived, but he developed locked-in syndrome. Case 3: a 53-year-old man, who developed transient apnea after an injury. On admission, neurological examination showed horizontal nystagmus, weakness of his right upper limb, and sensory disturbance in the left side of the body. Neck traction was done for spinal C1 and C2 fractures. Twenty one hours after the injury, he became comatose suddenly. The four-vessels angiography revealed the occlusion of both vertebral arteries. The basilar artery was visualized through the posterior communicating arteries. He died on the 6th day after the trauma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2594156 TI - [A case of intracranial osteochondroma: its MR images]. AB - A 15-year-old boy was referred to our department due to left abducens palsy and trigeminal neuralgia. CT scans that had been taken fourteen months before this referral failed to disclose any abnormality. CT scans taken on admission, however, demonstrated an irregular calcified lesion in the left parasellar region. This implied that some ossifying process had been progressing during these fourteen months. MR images clearly demonstrated tumor contour and it was shown that high and low intensity spots were evenly scattered within the tumor. Consequently, tumor appearances in MR images were totally different from those in CT scans. MR images were useful in investigating contour and extension of osteochondroma, but CT scans were necessary to locate calcified foci within the tumor. PMID- 2594155 TI - [A case of calvarial metastasis of thyroid carcinoma with intraorbital extension]. AB - A 63-year-old man came to our hospital with complaints of exophthalmos and a tumor in the right temporal region. Physical examination revealed not only these findings but also a tumor in the right lateral side of the neck. Plain skull X ray showed radiolucent area with irregular non-sclerotic margin in the right temporal region of the skull and erosion of the lateral half of the right minor sphenoid wing. Post-contrast CT demonstrated a homogeneously enhanced tumor in the right temporal region with extracranial and intracranial extension, partly invading the right orbita, which compressed the eyeball anterioinferiorly. On MRI (TR 500msec, TE 30msec), the tumor showed an isointensity area with a thin rim of low intensity. Right external carotid angiography revealed the numerous tumor vessels fed by the middle meningeal artery, the accessory meningeal artery and the anterior branch of the superficial temporal artery. On right internal carotid angiography, it was shown that the branches of the right ophthalmic artery were also feeding the tumor. 99Tc scintigraphy demonstrated the areas of increased radionuclide concentration in the skull and neck lesion. Preoperative embolization of the tumor vessels fed by the external carotid artery system was performed. Chopped gelfoam serving as embolization material were injected through a transfemoral catheter, selectively placed into the external carotid artery. Following this procedure, the numerous tumor vessels disappeared completely. PMID- 2594157 TI - [Spontaneous spinal epidural hematoma diagnosed by MRI: a case report]. AB - Appropriate diagnostic procedure for spinal epidural hematomas has not been established yet. The authors reported a case of spontaneous epidural hematomas at the thoracic level, in which correct diagnosis was made with MRI and good results were obtained by surgery. A 63-year-old female experienced a severe back pain which appeared suddenly during a walk and was followed by motor weakness in both legs deteriorating quickly to paraplegia. The patient had no history of hypertension, trauma or bleeding tendency. The laboratory data were normal. On admission, neurological examination revealed flaccid paraplegia, total sensory loss below the level of Th 6 and urinary and fecal incontinence. Myelograms showed incomplete block at the Th 6 level and postmyelographic CT scan showed an isodense mass, which was suspected to be an epidural tumor located behind the spinal cord. Emergent MRI confirmed an epidural hematoma as a high intensity area extending from Th 3 through Th 11. Sixty-five hours after onset, laminectomy of Th 4 through Th 11 and the evacuation of epidural hematoma were performed without identification of the origin of the bleeding. Neither vascular malformation nor tumor was recognized during operation. Neither was it noticed on histological examination. The patient made favorable progress after the surgery. During the first two weeks in the postoperative period, she regained muscle strength enough to do standing exercise, and satisfactory improvement was made in sensory function including urination and defecation. We emphasize that MRI is indispensable to make a differential diagnosis of thoracic lesions. In the reported case, a correct diagnosis was made with MRI, and an extremely good result was obtained by an emergency operation. PMID- 2594158 TI - [Osteoblastic skull metastasis of lung cancer]. AB - A case of osteoblastic skull metastasis of lung cancer is reported. A 56-year-old female patient was admitted to our hospital with complaints of headache and tumor of the right parietal bone. A plain skull X-ray showed hyperostotic feature of the right parietal bone. CT scan displayed that right parietal bone became thick and osteoblastic. Soft tissue was shown in the hyperostotic bone under MRI. An external carotid angiogram showed that the skull tumor was fed by the middle meningeal artery. The skull tumor and 2 solid intracerebral tumors were extirpated. Histological examination revealed adenocarcinoma in the skull and intracerebral lesions. The present case indicates that osteoblastic stimulating factor may be secreted by lung cancer. PMID- 2594159 TI - [The astrocyte-endothelial interface in cerebellar astrocytoma]. AB - The astrocyte-endothelial interface is a component of the anatomical blood-brain barrier in the central nervous system and is of interest in neoplastic lesions. We, therefore, investigated the fine structure of this interface in five, well differentiated cerebellar astrocytomas. The astrocyte-endothelial interface in cerebellar astrocytomas revealed various abnormalities. The perivascular space is usually wide and contains various amounts of collagen fibers, fibroblasts and pericytes. The basal lamina of the endothelial cell is mostly single-layered and continuous, but sometimes multilayered and discontinuous. The basal lamina of the neoplastic astrocytic cell is usually single-layered and continuous, but is occasionally absent in foci. The basal lamina of the endothelial cell is more prominent than that of the astrocyte. The neoplastic astrocyte has not so well developed cell junctions and poorly formed peripheral expansions of the processes. The relationship between the basal lamina of the endothelial cell and that of the astrocyte in cerebellar astrocytomas is compared to that in ependymomas. PMID- 2594160 TI - Evidence that physical dependence on morphine is mediated by the ventral midbrain. AB - Rats were given daily injections of increasing doses of morphine sulfate (40-100 mg/kg, s.c.), for 4 days. Twenty hours after the last injection of morphine, the animals received bilateral injections of naloxone (1-10 micrograms) into the substantia nigra, ventral tegmental area or sites 2 mm rostral, caudal or dorsal to the site in the nigra. Withdrawal signs were monitored for 20 min after the intracerebral injection. Naloxone administered into the nigra in morphine dependent rats produced dose-dependent significant increases in wet dog shakes, irritability to touch, teeth chattering, diarrhea and locomotion, compared to morphine-dependent animals that received injections of saline into the nigra. The injection of naloxone (3 micrograms) into the ventral tegmental area of morphine dependent animals, produced irritability to touch and diarrhea, compared to morphine-dependent controls that received saline in this region of the brain. Significant differences in withdrawal signs were observed between morphine dependent animals, that received injections of naloxone (3 micrograms) into the nigra and those that received naloxone (3 micrograms) into the ventral tegmental area or rostral or caudal sites. No differences between the substantia nigra and the dorsal sites were observed. However, withdrawal symptoms were produced by injections of naloxone into the substantia nigra and ventral tegmental area, even when the guide cannulae were angled to avoid penetration of sites dorsal to these regions of the brain. Naloxone, injected into the ventral midbrain of non dependent animals, produced no signs of withdrawal. These studies suggest that the ventral midbrain mediates physical dependence on morphine. PMID- 2594162 TI - Desipramine in small doses induces antinociception in the increasing temperature hot-plate test, but not in the tail-flick test. AB - The data reported for the antinociceptive effect of tricyclic antidepressants are conflicting. In this investigation, the effect of acute intraperitoneal (i.p.) administration of desipramine (2 and 5 mg/kg) was studied in rats, using the tail flick test with simultaneous measurement of tail-skin temperature, and the increasing temperature hot-plate test. A constant negative correlation between tail-flick latency and tail-skin temperature, as described earlier, was also found in this study. Different ambient temperatures influenced the results of the tail-flick test. At an ambient temperature of 24-25 degrees C, desipramine gave rise to an apparent antinociception in the tail-flick test, which was found to be caused by a relative fall in tail-skin temperature. At 21-22 degrees C, no change in tail-flick latency was found after the administration of desipramine. In the increasing temperature hot-plate test, however, a dose-dependent antinociceptive effect of desipramine was observed at both ambient temperatures. The strong influence of moderate differences in ambient temperature on the results of the tail-flick test may explain some of the conflicting results reported in the literature. Whenever this test is used, the temperature of the tail should be recorded and taken into account in the evaluation of the data. PMID- 2594161 TI - Cross-tolerance between morphine and clonidine: a study on motility in rats. AB - The effects of clonidine on motility were determined in non-dependent, morphine dependent (a 20 mg/kg dose i.p. for 26 days) and post-dependent rats. In naive animals, clonidine (30-100 micrograms/kg) produced a dose-related suppression of motility. However, when the drug was administered in morphine-dependent rats, it induced slight hyperactivity at small doses and a decrease of activity only at the largest dose (100 micrograms/kg). Thus, tolerance to morphine conferred cross tolerance to clonidine. On the contrary, the effects of clonidine on motility in post-dependent animals did not differ from those observed in control animals. The results are discussed in terms of similarities and differences between the depressant and excitatory effects of morphine and clonidine. PMID- 2594163 TI - Differential effects of methionine5-enkephalin on hippocampal pyramidal cells and interneurons. AB - While the excitatory action of opioids and opiate drugs upon pyramidal neurons in the hippocampus is well known, the mechanism by which this excitation is achieved is still argued. A popular hypothesis is that opiates reduce the activity of inhibitory interneurons, thereby indirectly exciting the pyramidal cells. To validate this idea, it is necessary to show that opiates selectively affect the population of interneurons. The present study therefore examined the effects of met-enkephalin upon pyramidal cells and interneurons located in area CA1. Extracellular action potentials were recorded using multibarrelled micropipettes. Drugs were applied locally by either pressure micro-ejection or microiontophoresis. Met-enkephalin (10(-5) M) elevated the spontaneous discharge of pyramidal cells, while interneurons were inhibited. The responses of both types of cell were blocked by the opiate antagonist naloxone. When the synaptic connections between the pyramidal cells and interneurons were disrupted by local application of magnesium or bicuculline, met-enkephalin had no effect on the pyramidal cells. However, neither magnesium nor bicuculline altered the enkephalin-induced inhibition of theta neurons. These results support the hypothesis that opioids of the enkephalin subclass, excite pyramidal cells in the hippocampus through a disinhibition mechanism. PMID- 2594164 TI - Effects of leu-enkephalin on the mechanical activity of longitudinal and circular muscles of the small intestine of the cat. AB - The effects of leu-enkephalin on the spontaneous and electrically-evoked activity were studied in the longitudinal and circular strips isolated from the duodenum, jejunum and ileum of the cat. Leu-enkephalin affected the spontaneous activity of both longitudinal and circular strips, with the exception of the circular strips from the ileum, in a naloxone-dependent manner. Elimination of the neural input to the smooth muscle cells with tetrodotoxin blocked the effects of leu enkephalin in the longitudinal and circular strips from the jejunum and in the longitudinal strips from the ileum. In the longitudinal strips from the duodenum the effect was resistant to tetrodotoxin, while in the circular strips a tetrodotoxin-sensitive component of the effect of leu-enkephalin was observed. Since leu-enkephalin evoked opposite effects in the longitudinal and circular layers of one and the same region, it is concluded that leu-enkephalin-induced modulation of the motility of the small intestine in the cat is a physiological phenomenon. Electrical stimulation, at a frequency of 5 Hz, evoked contractile responses in the longitudinal strips and relaxant, as well as low-amplitude, contractile responses in the circular strips. Rebound contractions developed after the end of stimulation in all preparations tested, with the exception of the longitudinal strips from the duodenum. Leu-enkephalin decreased the contractile components and tended to potentiate the relaxant components of the responses in a naloxone-dependent manner. Atropine inhibited the contractile components of the responses and significantly depressed the rebound contractions. Leu-enkephalin, applied after atropine, was ineffective suggesting that leu enkephalin-induced modulation was mediated mainly through interaction with cholinergic transmission. PMID- 2594165 TI - Cortical EEG changes during the self-administration of phencyclinoids. AB - Female rats, implanted with cerebrocortical EEG recording electrodes, were trained to self-administer cocaine and then ketamine under a fixed ratio 10 schedule of reinforcement, during limited access sessions. Periodically, a single unit dose of either phencyclidine (0.5 mg/kg), ketamine (4 mg/kg) or 1-(1 phenylcyclohexyl)morpholine (PCM 4 mg/kg) was substituted for ketamine, while the cortical EEG was recorded. Spectrum quantities of samples of EEG, taken immediately before and after each injection, were subjected to a discriminant analysis. For each drug, the preinjection state of the EEG could be classified separately from the postinjection state, using specific EEG spectrum quantities from the global frequency range (0.1-20 Hz). Furthermore, the relevant EEG parameters, which described the change from pre- to postinjection states, were unique for each drug (phencyclidine: total power and complexity; ketamine: peak frequency, relative power and mobility; PCM: all parameters except peak frequency), indicating potential differences in the EEG, occurring with a level of intake of drug which was controlled by the subject. Overall, these data serve to model the changes in the EEG that occur during the self-administration of three phencyclinoids. Furthermore, the combination of EEG spectrum analysis with discriminant analysis is useful in detecting subtle differences in the effects of these three drugs on the EEG. PMID- 2594166 TI - The metabolism of systemically-administered L-dihydroxyphenylalanine, by intact and dopamine-denervated striata, as revealed by brain microdialysis. AB - Idiopathic Parkinson's Disease arises from the progressive loss of dopamine (DA) utilizing neurons of the nigrostriatum and responds to the replacement of DA with L-dihydroxyphenylalanine (L-DOPA). In awake rats, with unilateral lesions induced with 6-hydroxydopamine (6-OHDA) of the DA-utilizing nigrostriatal pathway, treatment with L-DOPA causes the rapid onset of brisk contralateral turning behaviour. In urethane-anesthetized rats with identical unilateral lesions of the nigrostriatum, dialysis of the striatum, performed before and after the systemic administration of L-DOPA (25 mg/kg i.p.), did not demonstrate any alteration in extracellular DA in the striatum which was DA-deprived compared to intact striata. After treatment with L-DOPA extracellular levels of the metabolites of DA. DOPAC and HVA increased several fold. These results suggest: (a) DA neurons surviving after extensive lesions with 6-OHDA can compensate for loss of DA in the striatum and maintain extracellular fluid (and presumably synaptic) concentrations of DA; (b) in striata with extensive depletion of DA L-DOPA undergoes rapid decarboxylation to DA, followed by catabolism to DOPAC and HVA; and (c) in urethane-anesthetized animals, DA formed from DOPA does not appear to enter a releasable pool. PMID- 2594167 TI - Naltrexone blocks nicotine-induced prolactin release. AB - Two receptor populations involved in the release of prolactin were examined in conscious, freely moving, male rats bearing indwelling jugular cannulae. The intravenous administration of either nicotine or morphine increased plasma prolactin levels. Pretreatment with the nicotinic antagonist mecamylamine blocked the prolactin response to nicotine only. In contrast, the opiate antagonist naltrexone blocked the prolactin response to both nicotine and morphine. These findings indicate that the nicotine stimulated release of prolactin is dependent not only on functional nicotinic cholinergic receptors but on opiate receptors as well. This suggests that nicotine and morphine release prolactin via a common pathway containing nicotinic cholinergic and opiate synapses in series. PMID- 2594168 TI - Two transcranial Doppler studies on blood flow velocity in both middle cerebral arteries during rest and the performance of cognitive tasks. AB - While the middle cerebral artery (MCA) blood flow velocity changes relative to rest were assessed with transcranial Doppler sonography (TCD), 28 right-handed subjects with no sign of cerebrovascular disease performed two series of 6 cognitive tasks (two series = right and left MCA). The tasks included "reading", "finding nouns with a given first letter", and "multiplication" in four comparable versions to be performed aloud and silently in each of the two series. All of the tasks increased the MCA blood flow velocity bilaterally (2.7-12.1%). A significant left-right difference was present during "noun finding aloud" (left greater than right by 4.7%). A statistically insignificant tendency in the same direction was also present for the five other tasks. During loud reading the increase was higher bilaterally than during silent reading. Blood flow velocity changes in the right MCA for the three tasks performed aloud were lower in older than in younger people. It is posited that older people perform the tasks more slowly and under less stress requiring less right-hemispheric participation. Averaging the results for each of the four subjects involved leads to the conclusion that future TCD-lateralization studies should be done bilaterally at the same time to assess lateralization in a single person. PMID- 2594169 TI - Spatial attentional shifts: further evidence for the role of polysensory mechanisms using visual and tactile stimuli. AB - Normal subjects performed simple reaction time responses to lateralized visual target stimuli (Experiment 1) and lateralized tactile target stimuli (Experiment 2). In each experiment, the lateralized targets were preceded at one of four intervals by a visual or tactile cue located on the same (valid cue), or opposite (invalid cue) side, or on both sides (neutral cue). The validity of the visual and tactile cues influenced the speed of response to either target stimulus. These findings, together with those previously reported (Buchtel and Butter, Neuropsychologia 26, 499-509, 1988), are consistent with the view that intra- and inter-modal spatial cueing is effective with modalities that are linked to orienting systems in which movements of the sensory array serve to improve sensory analysis. PMID- 2594170 TI - Different error pattern of episodic and semantic memory in Alzheimer's disease and Parkinson's disease with dementia. AB - To evaluate the possible differences in memory dysfunction we analysed the episodic and semantic memory of patients with Alzheimer's disease (AD) and Parkinson's disease (PD) with dementia, and age-matched normal controls (NC). The memory was examined with story recall tests, list learning test with Buschke selective reminding method and category naming test. Both AD and PD groups committed more prior-story intrusion errors as compared with the NC subjects, but only the AD patients committed more extra-story intrusion errors. Both patient groups committed more extra-list intrusion errors than the NC group. Furthermore, the AD patients made more extra-list intrusion errors and recognized more false positive targets than the PD patients did. The results suggest that AD and PD patients have different patterns of memory dysfunction. The AD patients seem to perform poorly because of their inability to inhibit irrelevant information and because of increased sensitivity to interference, whereas the deficits of PD patients only reflect sensitivity to proactive interference. PMID- 2594171 TI - Amnesia and memory for modality information. AB - In this study, lists of words were used in a mixed-modality fashion (some read aloud by the subject, others read only by the experimenter). They were presented in this format to both Korsakoff amnesics and matched controls, with subjects only told to remember the words themselves. Controls and amnesics were matched on item-memory (forced-choice recognition) by using longer lists, tested at longer delays, for the controls. Despite this, however, the controls performed significantly better than the amnesics at modality-identification judgements about the items chosen during recognition. Whether the reported result reflects the memory deficit which causes amnesia, or whether it is more properly attributed to additional (frontal lobe) pathology present in only certain amnesics, is discussed. PMID- 2594172 TI - Voluntary vs autonomous control of repetitive finger tapping in a patient with Parkinson's disease. AB - Fourier analysis was used to investigate the role of perceptual information in controlling repetitive finger tapping in a patient with unilateral Parkinsonian tremor. The results are interpreted in the context of Von Holst's theory of relative co-ordination, and demonstrate the subject's reliance on extrinsic information to counteract tremor when performing voluntary repetitive movement. PMID- 2594173 TI - Lateralized dual-task performance: the effects of spatial and muscular repositioning. AB - In three experiments subjects were required to perform different manual tapping tasks using either the left or right hand while concurrently performing a speech task. The major independent variables examined were muscular effort and the spatial and muscular repositioning components of the tapping tasks. In all speech conditions right hand performance was disrupted more than left hand performance. The degree of this lateralized disruption did not alter as a function of variation in either muscular effort or the repositioning requirements of the manual task. However, muscular repositioning activity, unlike other components of the motor task, was affected bilaterally by the addition of the speech task. Overall the results suggest that the dual-task procedure can be used to assess two types of "lateralized" interference effects; one relating to right hand performance, the other to left hemisphere performance. PMID- 2594174 TI - Asymmetries in the perception of facial affect: is there an influence of reading habits? AB - Perceptions of happy facial affect from asymmetric composite faces presented in free vision were compared in four groups: left-to-right readers (Hindi), right-to left readers (Arabic), left-to-right and right-to-left readers (Hindi/Urdu) and illiterates (Hindi/Urdu). Right- and left-handed users of Hindi and Urdu were studied. The analysis of asymmetry scores revealed a significant effect of Group, such that a left hemifield preference was present only in the left-to-right (Hindi) group. There were no reliable differences between right- and left handers. Furthermore, the leftward bias was present in a significantly larger proportion of Hindi than Urdu or Arabic readers. These results are taken to reflect an interaction between a cerebral laterality effect and a directional scanning effect in facial affect judgment. PMID- 2594175 TI - Perceptual asymmetry for happy-sad chimeric faces: effects of mood. AB - Happy-sad chimeric face drawings were viewed in free vision by normal subjects. A significant and reliable perceiver bias toward the left hemiface when judging facial expression was found in right-handers whereas no consistent bias was found in non-right handers. This bias tended to be more pronounced in females. Subjects' current mood influenced their choice of facial affect but not their perceptual bias. In a further experiment, subjects were tested during induced elation and once more during induced depression. Again, though these moods increased the number of happy and sad choices respectively, the magnitude of the left hemifacial bias remained unchanged. The results are best explained by stable properties of the right hemisphere rather than arousal mechanisms. The implications of these findings are discussed in the light of the proposed hemispheric asymmetries in emotional perception and the possible lateralized effects of depressed mood on cognition. PMID- 2594176 TI - Laterality of motor response in visuo-spatial neglect: a case study. AB - We report a case of severe visuo-spatial neglect consequent upon right hemisphere stroke. At time of testing, the patient had a left visual field deficit and a very mild left hemiparesis. Star cancellation and line bisection performed with the right hand revealed profound left neglect; tested with the left hand, performance was only slightly impaired. The results are compatible with recent accounts of differential hemispheric activation provoked by lateralized pre-motor programming. PMID- 2594177 TI - Ambiguous-handedness: incidence in a non-clinical sample. AB - Using a handedness demonstration preference test under simple and complex task conditions, incidence rates for right, left, and mixed hand preferences were identified in a non-clinical sample. A relatively low incidence rate of ambiguous handedness was also demonstrated, supporting earlier hypotheses that this subtype is rare among normals. PMID- 2594178 TI - Duchenne muscular dystrophy carriers. Proton spin-lattice relaxation times of skeletal muscles on magnetic resonance imaging. AB - By means of magnetic resonance imaging (MRI), the proton spin-lattice relaxation times (T1 values) of the skeletal muscles were measured in Duchenne muscular dystrophy (DMD) carriers and normal controls. The bound water fraction (BWF) was calculated form the T1 values obtained, according to the fast proton diffusion model. In the DMD carriers, T1 values of the gluteus maximus and quadriceps femoris muscles were significantly higher, and BWFs of these muscles were significantly lower, than in normal control. Degenerative muscular changes accompanied by interstitial edema were presumed responsible for this abnormality. No correlation was observed between the muscle T1 and serum creatine kinase values. The present study showed that MRI could be a useful method for studying the dynamic state of water in both normal and pathological skeletal muscles. Its possible utility for DMD carrier detection was discussed briefly. PMID- 2594179 TI - MR evaluation of brachial plexus injuries. AB - Ten cases of brachial plexus injury were subjected to magnetic resonance (MR) to demonstrate the roots, trunks, divisions or cord abnormalities. Both normal and abnormal brachial plexuses were imaged in sagittal, axial, coronal and axial oblique planes. Myelography, using water soluble contrast agents, was performed in seven cases. MR demonstrated one traumatic meningocele, one extradural cerebrospinal fluid (CSF) collection, trunk and/or root neuromas in four, focal root fibrosis in two and diffuse fibrosis in the remaining two cases. Results of MR were confirmed at surgery in four cases with neuromas, while myelography was normal in two and was not carried out in the remaining two. In two cases, where MR demonstrated diffuse fibrosis of the brachial plexus, myelography showed C7 and T1 traumatic meningocele in one and was normal in the other. Both these patients showed excellent clinical and electrophysiological correlation with MR findings and in one of them surgical confirmation was also obtained. In the other two cases with focal nerve root fibrosis, myelography was normal in one and showed a traumatic meningocele in another. Operative findings in these cases confirmed focal root fibrosis but no root avulsion was observed although seen on one myelogram. Focal fibrosis, however, was noted at operation in more roots than was observed with MR. Initial experience suggests that MR may be the diagnostic procedure of choice for complete evaluation of brachial plexus injuries. PMID- 2594180 TI - MRI in cervical disk herniation. AB - Eleven operated herniated disks in 10 patients were evaluated preoperatively with plain films, myelography and magnetic resonance imaging. Plain X-ray was a valuable supplement to MRI for studying the bony changes. Myelography showed 7 of 11 herniated disks while MRI gave correct diagnosis in all. It is concluded that MRI can replace myelography and computerized tomography in the preoperative evaluation of cervical herniated disk. The other examinations may be supplementary in some cases. PMID- 2594181 TI - Imaging of brain metastases. Comparison of computerized tomography (CT) and magnetic resonance imaging (MRI). AB - For the demonstration of brain metastases both CT and MRI are available as diagnostic modalities. To compare both imaging methods as to their sensitivity in detecting brain metastases CT scans and MR images of 60 patients with suspected brain metastases were evaluated. Comparing contrast-enhanced CT and plain MRI neither modality was found to be clearly superior in this respect. PMID- 2594182 TI - Unusual MR manifestations of neurocysticercosis. AB - MR and CT features of neurocysticercosis are variable and depend fundametally on the stage in evolution of the infection, location, number and size of the worm. The authors retrospectively evaluated MR images obtained on a 2.0T superconducting unit in 22 neurocysticercosis patients and observed various MR features including some new findings. A variety of MR findings are presented with special reference to six case reports. The features include: (1) a large simple cyst containing both internal septations and a scolex; (2) suprasellar racemose cysts mimicking other cysts, (3) a fourth ventricular cyst readily depicted by aid of CSF flow-void in the sagittal plane; (4) degenerating cysts showing "white target" appearance; (5) granulomatous lesions having a "black target" appearance; and (6) a meningitic form showing Gd-DTPA enhancement of basal cisterns and of a subacute infarct. PMID- 2594183 TI - MR imaging of intracranial vertebral artery occlusion. AB - Magnetic resonance (MR) images of nine patients with intracranial vertebral artery occlusion (five proved, four presumed) have been reviewed. In two of nine, both vertebral arteries were occluded and in five of the nine, the basilar artery was also blocked. All occluded arteries showed absence of flow void and were clearly demonstrated as mildly hypo- approximately mildly hyperintense structures to brainstem parenchyma on the T1-weighted images. In two of five patients with basilar artery occlusion, retrograde filling of the distal basilar artery was detected. Thus, MR imaging, in particular the T1-weighted image, is a pertinent diagnostic modality for evaluating intracranial vertebral artery occlusion. Angiography does not seem to be required for confirmation. PMID- 2594184 TI - Anatomoradiological correlation of the intersection of the carotid siphon with the dura mater. AB - In order to obtain frames of reference to determine the place of intersection of the carotid siphon with the dura mater in conventional arteriograms, a debated topic lacking general agreement in the literature, 34 cadaveric sphenoids were prepared with the injection of radiopaque medium in both internal carotid arteries. After having marked the dura mater with steel wire, the pieces were radiographed in lateral view. The points of intersection of the clinoclinoid line and the sphenoidal line with the internal carotid artery as well as the emergence of the ophthalmic artery and its posterior projection were marked on the radiographs obtained. The distances between the various points were measured and submitted to statistical treatment. The results showed multiple regressions with a strong correlation coefficient in two equations. A table was built in which, knowing the distances between the points of the clinoclinoid and the sphenoidal plane lines and those of the ophthalmic artery and its projection, the position of the dura mater which covers the cavernous sinus may be estimated in arteriograms. PMID- 2594185 TI - Unbiased and efficient estimation of total ventricular volume of the brain obtained from CT-scans by a stereological method. AB - Using a simple stereological method the estimation of the ventricular volume in ten hydrocephalic children and adults based on ordinary CT-scans is presented. The volume estimates are compared with "ventricular size" expressed as Evans' ratio. The differences between the two estimates are discussed. PMID- 2594187 TI - Traumatic lumbosacral nerve root meningoceles. The value of myelography, CT and MRI in the assessment of nerve root continuity. AB - A case of traumatic lumbar meningoceles at four levels in combination with total and partial nerve root avulsion and with preservation of a nerve root is reported. Several diagnostic imaging techniques (myelography, CT, myelo-CT and MRI) are compared and their value in demonstrating the continuity of the nerve roots is discussed. MRI could assess the continuity of a nerve root in a traumatic meningocele, not demonstrable by myelography or myelo-CT. The combination of myelography, myelo-CT and MRI is likely to provide a complete diagnostic evaluation of nerve root lesions. PMID- 2594186 TI - An intravascular technique to occlude the middle cerebral artery in baboons. AB - A technique is described for occlusion of the middle cerebral artery in the baboon by an intravascular approach. A torque catheter is introduced under fluroscopic control into the internal carotid artery by transfemoral catheterization. In conjunction with a guide wire an infusion microcatheter with increasing stiffness from the distal tip to the proximal shaft is positioned in the proximal part of the middle cerebral artery via the introducer system. N Butyl-2-cyanoacrylate-monomers are injected into the microcatheter for permanent occlusion of the middle cerebral artery. The procedure was successfully completed in 21 out of 24 baboons. In 3 baboons the occlusion could not be achieved since the torque catheter could not pass proximal extreme tortuosities of possibly arterisclerotic internal carotid arteries. Infarcts in the 21 animals were confirmed by computerized tomography and/or autopsies in all animals. PMID- 2594188 TI - Amnesia due to bilateral hippocampal glioblastoma. MRI finding. AB - The authors report a unique case of glioblastoma which caused permanent amnesia. Magnetic resonance imaging showed the lesion to be limited to the hippocampal formation bilaterally. Although glioblastoma extends frequently into fiber pathways and expands into the opposite cerebral hemisphere, making a "butterfly" lesion, it is unusual for it to invade the limbic system selectively to this extent. PMID- 2594189 TI - Subacute sclerosing panencephalitis. Changes on CT scan during acute relapse. AB - A 19-year-old female patient presented in an acute state of akinetic mutism. Serological analysis of serum and cerebrospinal fluid demonstrated the presence of antibodies to measles virus. CT scan carried out during this acute phase of relapse demonstrated white matter enhancement affecting the cortical white matter of the frontal lobes and corpus callosum. These features indicate that active demyelination occurs during acute relapse in subacute sclerosing panencephalitis (SSPE) and suggest that immunotherapy should be considered during this acute phase. PMID- 2594190 TI - Giant aneurysm of the petrous carotid artery presenting with facial numbness. AB - We present the case of a 56-year-old man who complained of numbness in his cheek, and was shown to have a very large partly thrombosed aneurysm of the ipsilateral petrous carotid artery. The radiological findings and differential diagnosis are discussed. Aneurysm of the petrous carotid should be included in the differential diagnosis of any parasellar mass. PMID- 2594191 TI - Unilateral moya-moya disease: MRI findings. PMID- 2594193 TI - Imaging of cerebellar surface activation in vivo using voltage sensitive dyes. AB - The understanding of the information processing performed by complex neuronal networks in the central nervous system will require techniques permitting the simultaneous monitoring of the electrical activity of neuronal ensembles. Voltage sensitive dyes offer the potential for non-invasive optical monitoring of the activity in large populations of neurons. In this report we describe the use of voltage sensitive dyes and image processing techniques to monitor in vivo the activation of parallel fibers and associated neuronal events produced by stimulation of the cerebellar cortex in the rat. Despite the temporal limitations of video processing a relatively brief set of neuronal events was successfully imaged. Using this methodology we demonstrate that the detected fluorescent light changes were highly correlated with the evoked extracellular field potentials. Graded surface stimulation produced graded spatial patterns consistent with known parallel fiber anatomy and physiology. The optical signals were dependent on the presence of the voltage sensitive dyes and were abolished by topical application of a local anesthetic agent. In essence, activation of a parallel fiber beam and associated activity were imaged at relatively high resolution. PMID- 2594192 TI - Aspergillosis of the sphenoid sinus with cavernous sinus syndrome. PMID- 2594195 TI - Basic fibroblast growth factor promotes in vitro survival and cholinergic development of rat septal neurons: comparison with the effects of nerve growth factor. AB - The effects of basic fibroblast growth factor and nerve growth factor on survival and transmitter expression of cultured rat embryonic (E18) septal neurons were studied. Two different culture media were used: (i) a horse serum-containing Leibowitz L-15 medium and (ii) a serum-free N1-supplemented Dulbecco's modified Eagle's medium. Addition of basic fibroblast growth factor to either culture medium enhanced neuronal survival in low density cultures after 4 days. The effects of basic fibroblast growth factor were dose-dependent and blocked by anti basic fibroblast growth factor antibodies. In serum-containing L-15 medium nerve growth factor also promoted neuronal survival. Basic fibroblast growth factor and nerve growth factor supported neurons comprised both cholinergic and GABAergic subpopulations. The effects of basic fibroblast growth factor and nerve growth factor were not additive. In high density cultures using serum-containing L-15 medium survival of septal neurons was four times higher than in low density cultures after 4 days. Addition of basic fibroblast growth factor or nerve growth factor did not further augment neuronal survival in high density cultures. Maintenance of septal neurons at high density was not affected by antibodies to basic fibroblast growth factor and/or nerve growth factor. Addition of basic fibroblast growth factor or nerve growth factor to serum-containing L-15 medium at high cell density significantly enhanced choline acetyltransferase activity 3- and 7.5-fold, respectively, without affecting cell survival. In conclusion, next to nerve growth factor, basic fibroblast growth factor, which has been located in the hippocampal target area of septal neurons, appears to be another potent trophic factor for septal neurons. PMID- 2594194 TI - Antidromic firing occurs spontaneously on thalamic relay neurons: triggering of somatic intrinsic burst discharges by ectopic action potentials. AB - Eighty-two identified thalamocortical relay neurons were recorded extracellularly in the ventral posterior thalamic nucleus in 29 urethane-anaesthetized rats. Electrical stimulations were applied to the contralateral vibrissae or to the ipsilateral neocortex for ortho- or antidromic activation. The critical period following a known somatic action potential and during which no antidromic response could reach the soma was systematically determined for each cell using a collision test. Thus, the possible ectopic axonal origin of a given impulse could be determined. Thalamic neurons displayed either tonic or phasic firing modes, the latter characterized by episodes of rhythmic high-frequency burst discharges. The present results suggest that such bursts were generated at the soma and probably involved an intrinsic mechanism, since: (1) a modulation of the somatic excitability with an excitatory or inhibitory amino acid affected the intra-burst structure; (2) an antidromic test action potential collided with the second or any of the later impulses of such bursts; (3) an orthodromic activation could evoke a burst structurally similar to a natural one; and (4) the duration of the first interval of such an evoked burst was always inferior to the sum of the critical period plus the antidromic conduction time, ruling out the possibility that it might have been entirely ectopically generated on thalamic terminals. The results further show that a spontaneous ectopic axonal impulse could trigger a somatic burst, since: (1) an electrically-evoked antidromic action potential could trigger a burst structurally similar to a spontaneous one; (2) on 42% of the tested thalamic cells, a known antidromic action potential delivered during the critical period following a spontaneous single impulse could not collide with it: in many cases such non-collisions were seen with the first action potential of a burst; and (3) with increasing ionophoretic doses, GABA could: (i) convert bursts to single action potentials, while the ortho- but not the antidromic responses were abolished, (ii) block these single impulses at similar doses than those which abolished known antidromic ones, and (iii) multiply by a factor of 3 the probability of testing an ectopic action potential. On 70% of the cells tested, such GABA-isolated impulses could be proved to have been ectopically generated. Finally, ectopic impulses have never been observed during periods of tonic firing, indicating that such a feature was not an experimental artifact.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2594196 TI - A dopaminergic inhibitory postsynaptic potential mediated by an increased potassium conductance. AB - Intracellular recordings from intact pituitary melanotrophs show that, in the same cell, inhibitory postsynaptic potentials resulting from either pituitary stalk stimulation or exogenous dopamine are abolished by D2 receptor antagonists, display identical conductance changes, are reversed in polarity at the same membrane potential and are sensitive to pertussis toxin pretreatment. The reversal potential of the inhibitory postsynaptic potential shows a 65 mV shift with a 10-fold change in external potassium concentration, which is close to that predicted by the Nernst equation. We conclude that activation of this synapse releases dopamine which acts on a D2 receptor to increase potassium conductance via a G-protein-mediated mechanism. This is the first characterization of an inhibitory dopaminergic synapse in the mammalian nervous system. PMID- 2594198 TI - Two calcium-binding proteins mark many chick sensory neurons. AB - The first immunohistochemical results with a new neuronal calcium-binding protein, calretinin, are presented. Calretinin is related to the 28,000 mol. wt calcium-binding protein, calbindin, and a survey of the chick brain by in situ hybridization has identified the brain nuclei that expressed the genes for the two proteins [Rogers J.H., J. Cell Biol. 105, 1343 (1987)]. Now, antisera have been raised against calretinin fusion proteins in order to visualize individual neurons. The antisera have been used in an immunohistochemical survey of calretinin and calbindin in the chick sensory nuclei and ganglia, where these two proteins are found to be particularly prevalent. In the central nervous system, they are seen in many secondary sensory neurons and local circuit neurons, the two proteins being almost always in separate cells. However, in ganglion cells of the spinal nerves, inner ear, and retina, they are often expressed together. Their distribution in the brain is generally different from that of a third calcium-binding protein, parvalbumin. These proteins may modulate many important calcium-dependent processes in neurons, and probably have multiple functions. PMID- 2594197 TI - The plant lectin soybean agglutinin binds to the soma, axon and central terminals of a subpopulation of small-diameter primary sensory neurons in the rat and cat. AB - The distribution of binding of the plant lectin soybean agglutinin to primary sensory neurons has been investigated in the rat and cat. Soybean agglutinin was found to bind to approximately 30% of neurons in the fourth, lumbar dorsal root ganglion of the rat and approximately 50% of neurons in the first, sacral dorsal root ganglion in the cat. Morphometric analysis of these dorsal root ganglia revealed that in both species those neurons which bind soybean agglutinin appear to be a subpopulation of the small-diameter cells. Electron microscopic analysis of the lumbar dorsal roots revealed that soybean agglutinin binds to the plasma membrane of a subpopulation of unmyelinated axons in both species. Myelinated axons did not bind the lectin. In the dorsal horn of the spinal cord, soybean agglutinin bound to components of Lissauer's tract and the superficial laminae (laminae I and II) of the dorsal horn in both species. In the dorsal horn lectin binding was limited to lamina I and the outer portion of lamina II (sublamina IIo) in the cat, while in the rat lamina I and the entire dorsoventral extent of lamina II (sublaminae IIo and IIi) were labelled. Thirty days following dorsal rhizotomy, soybean agglutinin binding in the superficial dorsal horn, ipsilateral to the rhizotomy, was abolished in both species. These results show the plant lectin soybean agglutinin to be a histochemical marker for the soma and central terminals of a subpopulation of small-diameter sensory neurons in both the rat and cat. It is suggested that soybean agglutinin binding may be used in conjunction with immunohistochemistry to allow identification of putative neurotransmitters within, or in synaptic profiles associated with, the central terminals of small-diameter primary sensory neurons. PMID- 2594199 TI - Immunoreactivity for calretinin and other calcium-binding proteins in cerebellum. AB - Two calcium-binding proteins, calbindin and parvalbumin, have been reported to be abundant in Purkinje cells and other cell types in the cerebellum. Immunoreactivity for a related protein, calretinin, is now reported in cerebellum of chick and rat. In the chick, antibodies against calretinin stain mossy fibres throughout, and climbing fibres in a distinct group of folia. They also stain several cell types in the molecular layer. As there is no detectable calretinin mRNA in the cerebellar cortex, this cellular staining may be due to cross reaction with an unknown antigen. In the rat, antibodies against calretinin stain the Lugaro cells, and some granule cells in lobe X; they also give weak staining of all the granule cells in the other lobes. Thus almost all the neuronal cell types in the cerebellum show immunoreactivity for at least one of the calcium binding proteins in one or both species. PMID- 2594201 TI - GABA-immunoreactive neurons in the dorsal horn of the rat spinal cord. AB - An antiserum to GABA was used on semithin resin-embedded sections of rat dorsal horn. Immunoreactive neurons were evenly distributed throughout laminae I-III and constituted between 24 and 33% of the total neuronal population within three laminae. Fifty Golgi-stained cells in lamina II were tested with the antiserum. Most of the islet cells examined were immunoreactive, although some small islet cells were not. None of the 14 stalked cells tested was immunoreactive. These results provide further evidence that the stalked and islet cells of lamina II form two distinct functional classes and suggest that the islet cells function as inhibitory interneurons. PMID- 2594200 TI - Ascending projections from the solitary tract nucleus to the hypothalamus. A Phaseolus vulgaris lectin tracing study in the rat. AB - The course of the ascending pathways originating from the anterior gustatory and posterior visceral sensory part of the solitary tract nucleus and the topographic organization of the projections to the hypothalamus in the rat were studied with anterogradely transported Phaseolus vulgaris lectin. In general, the posterior visceral sensory part of the solitary tract nucleus has ascending projections as far as the septum-diagonal band complex and gives rise to heavy input to the bed nucleus of the stria terminals, and to the dorsomedial and paraventricular hypothalamic nuclei. A more moderate projection is aimed at a variety of other hypothalamic nuclei, to the medial and central amygdaloid nuclei and to the paraventricular nucleus of the thalamus. The ventromedial hypothalamic nucleus is strikingly missing an afferent input from the nucleus of the solitary tract. Furthermore, it was shown that whereas the caudal solitary tract nucleus has predominant long ascending connections, the projections from the anterior taste related region of the nucleus of the solitary tract have only limited forebrain projections which do not reach beyond the level of the anterior dorsal hypothalamic nucleus. PMID- 2594202 TI - Serotonergic neurons in the intestine of two teleosts, Carassius auratus and Oreochromis mossambicus, and the effect of serotonin on transepithelial ion selectivity and muscle tension. AB - The application of an antiserum directed against rat serotonin demonstrated serotonin-immunoreactive cell bodies and varicose nerve fibres in the myenteric plexus of both goldfish and tilapia. In the circular muscle layer immunoreactive varicose nerve fibres and a few cell bodies could be detected. A fine network of varicose fibres was observed underlying the epithelial cells. Serotonin immunoreactivity was not observed along incoming mesenterial blood vessels, suggesting that the serotonergic neurons may be intrinsic to the intestine. Immunoreactive endocrine cells were shown in the intestinal epithelium of tilapia but not in goldfish. Serotonin caused a weak contraction of the intestinal wall of the goldfish which could be blocked by tetrodotoxin and by atropine, suggesting that serotonin has an indirect action on muscular contraction. In contrast, serotonin induced a relaxation of the intestinal wall of tilapia which could not be blocked by propranolol or by tetrodotoxin. This indicates that in this species serotonin may act directly on the muscle fibres. The ion-selectivity of the intestinal epithelium of both species was modulated by serotonin. Tetrodotoxin did not inhibit this effect, suggesting that serotonin acts directly on the epithelial cells. The presence of serotonergic fibres in the muscle layer and directly underneath the epithelium, along with the effect of serotonin on muscular tension and on the ion-selectivity of the epithelium, suggests that serotonin may play a role in the regulation of motility and the epithelial function of goldfish and tilapia intestine. PMID- 2594203 TI - SPECT bone scintigraphy of benign and malignant lesions of the spine. AB - 70 patients were examined with planar and SPECT bone scintigraphy. SPECT proved to be superior over planar bone scanning for imaging of traumatic, inflammatory, and malignant bone lesions. SPECT provides three-dimensional information and, therefore, delineates the exact location and extension of lesions. It also has a higher sensitivity than planar bone scintigraphy. The three-dimensional bone scan generates complementary diagnostic information which often facilitates an adequate therapy protocol. PMID- 2594204 TI - Surgical treatment of myeloradiculopathy in cervical spondylosis. A report on 438 operations. AB - In the past eleven years we have performed 438 microsurgical ventral discectomies with bilateral foraminotomy followed by fusion with palacos in the cervical spine in our clinic. An analysis of the preoperative symptoms shows a great variability and overlapping of the various segments. To determine the right level for the operation it is crucial that the results of the clinical and the radiological examinations be evaluated. The results of ascending myelography and CT scans are of great value. In cases of cervical myelopathy a multisegmental operation is often necessary to obtain good results. The complication rate was small in our patients and a second operation was only necessary in a few cases. We had very good postoperative results in radicular pain and muscle weakness. In patients with symptoms of cervical myelopathy we achieved considerable improvement. PMID- 2594205 TI - Surgical treatment of lumbar stenosis: long-term results. AB - Lumbar stenosis is a disease of the elderly which is due, in the majority of cases, to degenerative changes. This disease causes considerable disability which cannot be ameliorated well by conservative treatment. Surgery is usually the treatment of choice, although long-term results have been reported in only a few publications. We attempted a reevaluation of our patients one to seven years after intervention. Overall results indicate that about 80% of our patients benefited from surgery in varying degrees. Only 10% showed post-operative deterioration. One third of operated cases achieved complete working or functional capacity, while in the remaining cases disability persisted. Since long-term results are similar in patients over and under 65 years of age, intervention is recommended even in the older patient if his general condition is good enough to allow surgery. PMID- 2594206 TI - Prophylaxis of postoperative lumbar spondylodiscitis. AB - Spondylodiscitis after lumbar disc surgery is a well-known complication with a frequency of 0.1 to 3%. According to the authors, the etiological factors are: combination of operated segment instability, damage to the lower and upper plates due to disc space curettage and transmission of germs. After treatment of 100 selected cases, all with increased risk of postoperative spondylodiscitis, distinct possibilities for prevention have been discovered. Basic treatment consisted of 3 x 80 mg perioperative doses of Gentamicin i.m. In addition a collagen sponge (Sulmycin Implant) containing 50 mg Gentamycin was inserted in the cleared disc spaces of 50 patients. Complications in this procedure were not observed. The following is recommended for prevention of postoperative spondylodiscitis: a careful operating technique, perioperative antibiotics, and in particularly endangered patients, insertion of Sulmycin Implant in the disc spaces. PMID- 2594207 TI - Spinal cord compression caused by plasmocytomas. A retrospective review of 14 cases. AB - Plasmocytoma is a plasma cell tumor, which occurs in various structures of the body. When the spinal column is involved, it may cause cord compression. In this study, 14 cases of spinal plasmocytomas are presented. Seven of them were male and seven female. The major complaints were pain in twelve cases, motor weakness in eight cases, and bladder disturbance in six cases. On neurological examination, twelve of the patients had impairment of extremity movements (85.7%), and eight had sensory losses (57.1%). Compression was more frequent in the thoracic region. There was a total block in nine and partial block in five cases. All patients underwent surgery. In thirteen cases laminectomy was performed, in one thoracotomy. In this report, complaints, clinical and laboratory findings, neurological examination, and histopathology of our cases are reviewed and the results discussed. PMID- 2594208 TI - Intramedullary pilocytic astrocytomas--a clinical and morphological study after combined surgical and photon or neutron therapy. AB - Ten patients suffering from intramedullary pilocytic astrocytomas (WHO classification: astrocytoma grade I) were investigated catamnesticly. Combined surgery and radiotherapy was performed. Seven patients received neutron irradiation postoperatively. In four cases the neurological symptoms were improved after follow-up periods ranging from 33 to 89 months. The three other patients died after 6 to 21 months. The autopsy findings of a 14 year old child are presented. Our results are compared with reports in the literature. In addition, long-term problems of the spinal column are discussed. It seems that the combined surgical and neutron therapy improves the prognosis of pencil gliomas. PMID- 2594210 TI - Infant stress and coping. PMID- 2594209 TI - Fine structural features of the cerebral microvasculature in hydrocephalic human infants: correlated clinical observations. AB - Four of 30 human cerebral cortex biopsies from infants ranging from four days to about ten years treated for hydrocephalus by shunt operations are described paying special attention to the vascular structures. The biopsy specimens were studied in semi-thin and ultrathin sections. Attention is drawn to the role of pinocytotic vesicles found in capillaries and smaller vessels as a possible transcellular route for the hydrocephalic oedema resolution. No intercellular dehiscences or the so called blisters were observed. With the passage of time, the number of membrane bound vesicles increased and arrays of pinocytotic vesicles were discernible both on the abluminal as well as luminal aspect of the capillary wall. Additionally, larger vacuoles containing electron-dense material, apparently undergoing autolysis, were also detected. The basal lamina was of uneven thickness and at places duplicated. Hypertrophic pericytes exhibited remarkable oedamatous changes, increased vesicular or vascular transport, demonstrating pericyte brain-barrier dysfunction. Swelling of the astrocytic end feet bordering the capillaries was remarkable. These findings indicate that the CSF or oedema fluid is absorbed into the vascular system via a transendothelial pathway. PMID- 2594211 TI - Behavioral features of early reactivity: antecedents and consequences. PMID- 2594213 TI - GABAergic hippocampal neurons resistant to ischemia-induced neuronal death contain the Ca2(+)-binding protein parvalbumin. AB - Bilateral transient occlusion of carotid arteries in gerbils for 7 min results in delayed neuronal cell death in hippocampal field CA1. Local gamma-aminobutyric acid (GABA)ergic neurons survive the ischemic insult. Here we show that interneurons in gerbil hippocampus are parvalbumin-immunoreactive, that they contain the GABA-synthetizing enzyme glutamic acid decarboxylase (GAD), and that they are resistant to the effects of ischemia, being present up to 28 days after the insult. It might be concluded that the presence of the Ca2+-binding protein parvalbumin protects the GABAergic neurons from the deleterious consequences of ischemia-induced excitotoxin-mediated Ca2+-influx. PMID- 2594212 TI - Presence of Schwann cells in neurodegenerative lesions of the central nervous system. AB - Ultrastructural analysis of neurodegenerative CNS lesions produced by an excitotoxic substance revealed that the majority of cells ensheathing axons were not oligodendrocytes. By their morphology and the presence of both a basal lamina and collagen fibers they were identified as Schwann cells. The presence of Schwann cells, whose growth-promoting role in the peripheral nervous system has been largely documented, may account for the development of regenerating growth cones which have been observed in the excitotoxically lesioned central nervous system. Further support for this hypothesis came from the analysis of fetal neural transplants implanted into the lesioned area. Schwann cells ensheathing axons were indeed numerous in the neuron-depleted area surrounding the transplants, where neurite outgrowth of graft origin occurred. PMID- 2594214 TI - Change in calcium permeability caused by quinolinic acid in cultured rat hippocampal neurons. AB - The calcium permeability of receptor channels activated by quinolinic acid (QUIN) in cultured rat hippocampal neurons was investigated using the whole-cell voltage clamp method. In Na+-free, 10 mM Ca2+ solution with the internal solution containing 165 mM Cs+, QUIN elicited prominent inward currents at -60 mV, and the reversal potential of the QUIN-induced current was -5.8 +/- 1.2 mV, indicating that QUIN-activated channels are highly permeable to Ca2+ (permeability ratio PCa2+/PCs+ = 5.9). This result was substantiated by microfluorometry using fura 2, which revealed that QUIN caused a marked increase in the intracellular Ca2+ concentration even after the voltage-dependent Ca2+ channels had been suppressed by La3+. PMID- 2594215 TI - Distribution of cell bodies for primary afferent fibers from the stomach of the cat. AB - The distribution of primary afferent cell bodies supplying the stomach of the cat was localized using lectin-conjugated horseradish peroxidase. Labelled cells were found in the nodose ganglia and dorsal root ganglia T4-L2 or T4-L1. The spinal entry levels of the stomach afferents do not overlap extensively with those of the cardiac afferents. PMID- 2594216 TI - Ciliary neurotrophic factor supports target-deprived preganglionic sympathetic spinal cord neurons. AB - Spinal cord neurons in the intermediolateral column (IML) that innervate the adrenal medulla require target-derived factor(s) for their maintenance in vivo. Selective destruction of the adult rat adrenal medulla causes an approximate 25% loss of Nissl-stained IML neurons between spinal cord levels Th 4 weeks after surgery. We have previously suggested that basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF) or closely related molecules are present in adrenal chromaffin cells and granules. Basic FGF supplemented in gelfoams to the medullectomized adrenal gland fully prevented IML neuron losses. These results are now extended by demonstrating that (i) CNTF administered in vivo (7.2 micrograms/gelfoam) also rescues IML neurons, and (ii) the rescue effect is abolished by splanchnicotomy, i.e. interruption of axonal pathway from the spinal cord to the adrenal gland. These data would be consistent with CNTF being a retrograde trophic messenger to the spinal cord, but do not exclude the possibility that CNTF mimics or induces the formation of an endogenous trophic factor. PMID- 2594217 TI - Increase in choline acetyltransferase activity in septum of rats after transient forebrain ischemia: a possible role of factors released in the hippocampus. AB - Choline acetyltransferase (ChAT) activity increased in rat septum 2 weeks after a transient forebrain ischemia. Extracts were prepared from hippocampus in which CA1 pyramidal neurons had been selectively destroyed by the ischemic insult. ChAT activity in septal neuronal cultures treated with these extracts for 6 days was significantly higher than that in control cultures. PMID- 2594219 TI - Carbachol injection into the medial preoptic area induces natriuresis, kaliuresis and antidiuresis in rats. AB - The microinjection of carbachol into the medial preoptic area (MPO) of the rat induced natriuresis, kaliuresis and anti-diuresis in a dose-related manner. Atropine blocked all responses to carbachol. Hexamethonium impaired the dose response effect of carbachol on kaliuresis, but had no effect on natriuresis and enhanced the antidiuretic effect of carbachol. Nicotine alone had no effects, but pre-treatment with nicotine enhanced the responses to carbachol. These data show that activity of the muscarinic receptors of the MPO increases renal electrolyte and reduces water excretion. They also suggest that nicotinic receptors have an inhibitory effect on water excretion. Nicotine could act through mechanisms unrelated to nicotinic receptors to enhance the effect of the carbachol. PMID- 2594218 TI - Effect of kindling on potassium-induced electrographic seizures in vitro. AB - The properties of high [K+]o-induced spontaneous bursting and electrographic seizures in hippocampal slices prepared from rats subjected to kindling from either the lateral entorhinal cortex or the angular bundle were compared to those in control slices. Kindling enhanced the frequency of K+-induced burst-firing in the CA3 region and the duration of triggered bursts in the dentate gyrus, as previously reported. However, kindling had no influence on the characteristics or occurrence of electrographic seizures in the CA1 region of slices bathed in elevated [K+]o. In addition, the development of electrographic seizures in slices from control animals did not require a preconditioning period of burst input from the CA3 region. PMID- 2594220 TI - Striatal dopaminergic toxicity following intranigral injection in rats of 2 methyl-norharman, a beta-carbolinium analog of N-methyl-4-phenylpyridinium ion (MPP+). AB - Methylated beta-carboline compounds are mammalian indole metabolites that we have proposed to be endogenous neurotoxins due to their structural similarity to MPP+, the active oxidized product of the dopaminergic toxin, N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). Several laboratories have demonstrated that MPP+ administration into the substantia nigra or median forebrain bundle of rats results in extensive depletion of striatal dopamine and its metabolites. We now report that three weeks after intranigral injection of the beta-carboline, 2 methyl-norharman, striatal dopamine, DOPAC, and homovanillic acid (HVA) concentrations ipsilateral to the injection are reduced 41-64% compared to vehicle-injected controls; in individual animals dopamine depletions of 96% were achieved. In addition, at the 2-methyl-norharman injection site in the substantia nigra, large lesions and gliosis were apparent under light microscopic examination. This is the first direct demonstration that a 2-methyl-beta carbolinium ion is neurotoxic. It lends further validity to the hypothesis that MPP+-like beta-carbolines may be endogenous causative agents in Parkinson's disease. PMID- 2594221 TI - Modification of human spinal stretch reflexes: preliminary studies. AB - Modulation of the human spinal stretch reflex (SSR) may be important in treating hyperactive reflexes or may be a tool to enhance normal performance. Eight of 9 subjects given feedback of biceps brachii SSR amplitude and instructed to increase (uptrain) or decrease (downtrain) this response were able to do so in the appropriate direction. These results imply that, as in non-human primates, SSR amplitude can be modified. PMID- 2594222 TI - Unsuccessful treatment course not malpractice. PMID- 2594224 TI - Epidemiology of congenital syphilis. AB - Between 1984 and 1987, the number of reported cases of congenital syphilis in New Jersey tripled. Findings indicate an increase in early syphilis among females of childbearing age living in areas of high syphilis morbidity, reflecting, possibly, lifestyle changes within populations already at risk for the disease. Future studies and interventions are needed. PMID- 2594223 TI - Asthma due to parasitic infestation. AB - The authors document the association between refractory asthma, eosinophilia, pulmonary infiltrates, and diarrhea due to parasitic hyper-infestation resulting from Strongyloides stercoralis. PMID- 2594225 TI - Physician service to Afghan refugees. AB - New Jersey physicians have been giving their expertise and invaluable skills to aid Afghan war victims. MSNJ members are responding with compassion and concern to this crisis. PMID- 2594226 TI - The multiple-choice test: writing the questions. PMID- 2594227 TI - Dealing with a student grievance. AB - How do faculty deal with a student grievance? When a student fails clinically and appeals that failure, how can faculty respond? The author presents a case history of a student grievance and describes statutory and case law, which underlie the practice of nurse educators. PMID- 2594229 TI - Enrollment management. AB - Attracting and retaining students in schools of nursing are of crucial importance to faculty. Although enrollment management functions are not part of the traditional faculty role, the authors describe how nursing faculty in a private liberal arts college instituted and implemented a successful enrollment management plan. PMID- 2594228 TI - The interactive journal: a clinical teaching tool. PMID- 2594230 TI - A strategy for introducing diagnostic reasoning: hypothesis testing using a simulation approach. AB - The ability to generate a number of hypotheses, so all possibilities in a situation are recognized, is a vital component in arriving at a correct nursing diagnosis. Students need learning experiences in this aspect of the diagnostic reasoning process. The authors discuss the four phase simulation method of teaching, which provides a useful model for developing beginning skills in hypothesis generation. PMID- 2594231 TI - The nursing licensure process and the NCLEX-RN. AB - Each profession is obligated to ensure society's safety. Licensure examinations must be valid and reliable measures of the knowledge necessary to practice safely in the profession. Nursing has an obligation to society for safe care and licensure is one way to guarantee this. Many changes have occurred in nursing licensure and many nurses are unfamiliar with them. The author traces these changes, describing and analyzing the current licensure examination. PMID- 2594232 TI - Developing procedures for students who refuse to care for a client. AB - The Human Immunodeficiency Virus (HIV) epidemic raised the question of whether students should be required to provide nursing care for clients whose diagnosis for treatments may jeopardize students' health. Policies and procedures are necessary to provide a framework of functioning for faculty and students when students question their patient assignment. The author explains one institution's successful process for developing a procedure which can facilitate development of appropriate policies and procedures by other faculty. PMID- 2594233 TI - She is a man: avoiding sexist language. PMID- 2594235 TI - Giving students control. PMID- 2594234 TI - Legacies, reminiscence, and ego-integrity. PMID- 2594236 TI - Shared wisdom through shared governance. PMID- 2594237 TI - Changes in mental handicap teams. PMID- 2594238 TI - How diet can be a handicap. PMID- 2594239 TI - Mental handicap. Taking stock of Project 2000. PMID- 2594240 TI - Mental handicap. Informed decision making. PMID- 2594241 TI - Mental handicap. Hepatitis B: a cause for concern. PMID- 2594242 TI - Are you happy to be a nurse? PMID- 2594243 TI - A model for Anna. PMID- 2594244 TI - Nursing patients with deep vein thrombosis. PMID- 2594245 TI - Nursing mothers with postnatal depression. PMID- 2594246 TI - Mirror images of anorexia. PMID- 2594247 TI - The use of seclusion. PMID- 2594249 TI - Anticipating suicide. PMID- 2594248 TI - Psychiatric nursing. PMID- 2594250 TI - Electrical activity of the heart. PMID- 2594251 TI - Delivery at home. PMID- 2594252 TI - Fractal analysis of ganglion cell dendritic branching patterns of the rat and cat retinae. PMID- 2594253 TI - Characterization of Rana germinal neuroepithelial cells in normal and regenerating retina. PMID- 2594254 TI - Cytoskeletal architecture of synaptic endings in the photoreceptor cells. PMID- 2594255 TI - Displaced and indoleamine-accumulating bipolar cells in the turtle retina. PMID- 2594257 TI - Photoreceptor-horizontal cell synaptic connections in teleost retina: electron microscopical survey of lucifer yellow-HRP double marking. PMID- 2594256 TI - Signal transfer from photoreceptors to bipolar cells in the retina of the tiger salamander. AB - Under conditions of dark-adaptation, in response to weak stimuli, the distal retina behaves as a linear system. During the process of voltage transfer from the rods to the bipolar cells the information encoded in the rod responses is spatially filtered. The spatial filtering is determined by the spatial properties of the receptive field of the bipolar cell. These, in turn, depend upon the spatial properties of three syncytia, those of the receptors, the horizontal cells and the bipolar cells themselves. The response of the bipolar cell to these weak stimuli is a linear difference of two components; a component generated by the receptive field center and a component generated by the receptive field surround. The receptive field surround is misnamed since it extends throughout the receptive field center and contributes to the response of the bipolar cell to stimuli located anywhere within the receptive field. The receptive field surround has the spatial properties that would be expected if it were generated by an input from the horizontal cells to the receptive field center of the bipolar cell. The cellular pathway mediating this input remains unclear though we have evidence that it involves, at least in part, a feedforward pathway from horizontal cells to bipolar cells. If a feedback pathway also exists it is not mediated by the GABAA synapse on the synaptic terminals of the cones. PMID- 2594258 TI - Transduction in primate cones. PMID- 2594259 TI - Health problems associated with urban poverty: a narrowing gap between the Third and First Worlds. PMID- 2594260 TI - Demolishing the lead danger. PMID- 2594261 TI - Resuscitation of cardiac arrest victims by advanced life support units in Monroe County, New York. AB - Four hundred sixty-three cases of cardiac arrest treated in the pre-hospital setting by advanced life support (ALS) or paramedic units in Monroe County, New York, were evaluated using Eisenberg's criteria, which define factors known to be critical for successful resuscitation. Forty-eight patients met the criteria of witnessed collapse and cardiopulmonary resuscitation (CPR) within four minutes and ALS within ten minutes, with the initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia. Of these, 16 (33%) patients were discharged from the hospital. This compares to 12 of 415 (3%) patients discharged who did not meet the criteria. Of the 171 patients who suffered witnessed arrests of cardiac origin, 20 survived to be discharged. This represents a successful resuscitation rate of 12%. These percentages are within the range noted for other ALS services in the United States. PMID- 2594262 TI - Paraesophageal hernia. AB - We have reviewed our experience with eight patients with paraesophageal hernias surgically repaired at this institution during an 18-month period. Three of these patients required emergent operation, and although the morbidity was higher in this group than in those undergoing elective surgery, no mortalities occurred in either group. The potential for the development of life threatening complications warrants immediate surgery on patients who are diagnosed to have paraesophageal hernias, even if asymptomatic. We recommend a transabdominal approach for the performance of a crural repair and an antireflux procedure. PMID- 2594264 TI - House staff stress and the impact of the new regulations on postgraduate medical education. PMID- 2594265 TI - The academic boycott of South Africa. PMID- 2594263 TI - Transient cortical blindness following an acute hypotensive event in the postpartum period. PMID- 2594266 TI - Lyme disease surveillance in New York State. PMID- 2594267 TI - Birth outcomes in New York State. PMID- 2594268 TI - AZT now being distributed free to children with AIDS. PMID- 2594269 TI - Risk of HIV transmission through blood transfusions is decreasing. PMID- 2594270 TI - Making more out of less. PMID- 2594271 TI - Knowledge development: pushing from within or pulling from without. PMID- 2594272 TI - The research process and the nursing process: distinctly different. PMID- 2594273 TI - An application of Orem's theory in nursing practice. PMID- 2594275 TI - Consciousness as a dissipative structure: an extension of the Newman model. AB - Newman's model of health as the expansion of consciousness and Prigogine's theory of dissipative structures provide the framework for the development of a model of consciousness as a dissipative structure. Relationships among Type A behavior, temporal orientation, and death anxiety are examined and explicated within the human field pattern of consciousness as a dissipative structure. Type A behavior, future orientation, and death anxiety are proposed as manifestations of consciousness with the potential to evolve to higher levels in accordance with Prigogine's theory. Preliminary research findings related to the model and suggestions for future research are also presented. PMID- 2594274 TI - Evaluation of two assessment techniques for adaptation to stress. AB - Two conceptual nursing models, Roy's adaptation model and Erickson and Swain's adaptive potential assessment model are explained, and knowledge is identified within these two assessment techniques for adaptation to stress. The purpose is to identify common, noteworthy areas of nursing science as well as areas where further development in nursing knowledge is needed. A case study is used to compare and contrast these models. When assessing adaptation to stress, one similarity between the approaches appears to be a propositional linkage that supports the influence of developmental level on basic need satisfaction. A divergent area between the two models identifies a need for further development in nursing knowledge regarding the adaptive potential status. This includes information pertaining to what an individual can reasonably do or be expected to do when contending with stressors. PMID- 2594276 TI - Human-pet interaction and loneliness: a test of concepts from Roy's adaptation model. AB - This research used two key concepts from Roy's adaptation model of nursing to examine the relationship between human-pet interaction and loneliness in nursing home residents. These concepts included (a) environmental stimuli as factors influencing adaptation and (b) interdependence as a mode of response to the environment. The hypothesis of this study asserted that the residents of a nursing home who had greater levels of interaction with a pet program would experience less loneliness than those who had lower levels of interaction with a pet. The study used an ex post facto nonexperimental design with 65 subjects. The simplified version of the revised UCLA loneliness scale was used to measure loneliness. Reported level of human-pet interaction was measured according to a four-point scale (1 = no interaction, 4 = quite a lot of interaction). The hypothesis was supported at the p less than 0.03 level of significance. Implications for practice through organizing pet programs in situations where loneliness exists are discussed. Recommendations for future research include replicating the study using a larger sample and developing a comprehensive human pet interaction tool. PMID- 2594277 TI - Factors affecting the use of mental health services in people with alcohol disorders. AB - In a preliminary analysis of data from a community survey of psychiatric disorders in urban Christchurch, 157 of the 1018 adults interviewed met diagnostic criteria for alcohol abuse and/or dependence. The subjects who met the criteria for alcohol abuse and/or dependence were more likely to have used mental health services than the population at large, although 39% of those with an alcohol disorder had never used any form of mental health service. We examined the impact of severity of alcohol disorder, duration of disorder and gender on the use of services among those with an alcohol disorder. Duration of disorder was not related to use of mental health services. Women are more likely than men to use these services. However, the most important finding was that those with the most severe disorders were most likely to have used mental health services. PMID- 2594278 TI - Cognitive impairment and its relationship to gait rehabilitation in the elderly. AB - In a prospective study of 116 elderly people admitted to a geriatric rehabilitation ward, mini-mental state score on admission was used to classify nonaphasic subjects into three groups: cognitively normal (24-30), mildly impaired (17-23) and severely impaired (less than 17). Forty-three percent of the subjects were normal, 34% had mild and 23% had severe cognitive impairment. Using walking speed as the index of gait rehabilitation, subjects with normal cognition had significantly greater gait improvement than those with cognitive impairment. Age and urinary incontinence did not contribute to predicting gait improvement in regression modelling. Cognitive impairment also predicted discharge placement to long term hospital care and to a higher level of care than the subject received prior to admission. Thus cognitive impairment on admission to a geriatric rehabilitation ward predicts poor rehabilitation outcome with respect to gait and discharge residence. PMID- 2594279 TI - Medical insurance and childhood general practitioner contacts. AB - The relationships between the duration of medical insurance coverage and rates of general practitioner consultations for morbidity were examined for a birth cohort of children studied to ten years. This showed that children from insured families had higher consultation rates even when due allowance was made for known social and economic factors correlated with the ownership of insurance. During the period from birth to five years children who were insured throughout the period made a mean of 19.16 consultations compared to 15.38 for the uninsured (p less than 0.001); during the period from five to ten years the insured made 13.07 contacts compared to 9.38 for the uninsured (p less than 0.001). The net effects of these trends were that children whose families had been insured throughout the ten year study period made a mean of nine more general practitioner consultations by the age of ten years than children from uninsured families. It is concluded that the presence of private medical insurance encourages the development of inequalities in childhood access to health care with children from insured families having greater access to care than children from uninsured families. PMID- 2594280 TI - Developing a national primary health care management information system. PMID- 2594281 TI - The Wellington Hospital smoking cessation clinic. AB - We evaluated a hospital based stop smoking programme which includes an initial assessment followed by six once-weekly group meetings. Optional use of nicotine containing chewing gum was chosen by 50% of subjects. The subject's abstinence was validated by personal interviews and measurement of blood thiocyanate and/or expired breath carbon monoxide levels. Ten intakes totalling 195 subjects have been followed for one year. Abstinence rates at the end of the six week course varied from 40% to 75% with a mean of 56%. At three months intakes had abstinence rates of 18% to 63% with a mean of 40%. At six months rates varied from 14% to 53% with a mean of 36% and at twelve months 5% to 47% with a mean of 32% were abstinent. Twenty-nine percent of those who elected to use Nicorette were abstinent at one year. PMID- 2594282 TI - Chatham Islands: 1981-83. PMID- 2594283 TI - A standard for ethics committees. PMID- 2594284 TI - The future of solo general practitioners. PMID- 2594285 TI - Home births. PMID- 2594286 TI - Changes to accident compensation. PMID- 2594287 TI - Christchurch child psychiatric unit. PMID- 2594288 TI - The congenital long QT syndrome. PMID- 2594290 TI - Low risk obstetric patients. PMID- 2594289 TI - A hypothesis about cot death. PMID- 2594291 TI - What nurses value. PMID- 2594292 TI - Confidentiality and disclosure of medical information. PMID- 2594293 TI - Job design: process and product. PMID- 2594294 TI - Community hospital merger: the challenge to nursing management. PMID- 2594295 TI - Step-by-step implementation of PCA therapy. Patient-controlled analgesia. (to avoid possible confusion with MeSH's PCA x-rsf.!). PMID- 2594296 TI - Co-primary nursing in the intensive care unit. PMID- 2594297 TI - Hospitals 1990: back to the future ... or else! PMID- 2594298 TI - Researchers to test AIDS drug. PMID- 2594299 TI - Balance communication, protection to solve industrial noise problem. PMID- 2594300 TI - Cool under fire. PMID- 2594302 TI - Reduce noise-induced hearing loss with precautions at home and work. PMID- 2594301 TI - Low-level radioactive waste disposal needs industrial hygiene expertise. PMID- 2594303 TI - Courts settle difficult questions regarding workplace drug testing. PMID- 2594304 TI - Lens wearers risk infection. PMID- 2594305 TI - Sexually transmitted diseases. PMID- 2594308 TI - The future of American medicine: busting the myths. PMID- 2594306 TI - Senseless! Senseless! Senseless! PMID- 2594307 TI - AZT to cost less. PMID- 2594310 TI - Legislature focuses on healthcare issues. Legislative update, 1989. OSMA Department of Legislation. PMID- 2594309 TI - Physicians' attitudes toward treating AIDS: how does your attitude measure up? PMID- 2594311 TI - The new AIDS legislation: how it affects you and your office staff. PMID- 2594312 TI - Medical eponyms. Cyclopia. PMID- 2594313 TI - Smoking cessation. AB - Cigarette smoking is the single largest preventable cause of premature death and disability in our society. Although the incidence of smoking has gone down in the last 20 years, it is still very prevalent among teen-agers. Several good methods of smoking cessation are available to the physician for use in his/her office. This article summarizes these methods and outlines a simple program of intervention which can be used in any primary care setting. PMID- 2594314 TI - A retrospective death certificate study of AIDS and AIDS-related conditions in Ohio: 1984-1986. AB - AIDS surveillance data are used routinely to define the magnitude of the epidemic, project future case numbers, delineate risk behaviors, and to assist in health planning and resource allocation. The purposes of this study are: (1) to evaluate the effectiveness of the Ohio Department of Health (ODH) AIDS Surveillance System in Ohio from 1984 through 1986 and (2) to identify additional cases which may have been overlooked through normal case identification procedures. A review of all deaths occurring in Ohio among males between the ages 20 and 50 was conducted for several diseases and conditions commonly associated with AIDS. PMID- 2594315 TI - American Academy of Optometry. Papers/posters/sections program. New Orleans, Louisiana, December 9-11, 1989. Abstracts. PMID- 2594316 TI - Condylar hyperplasia: cephalometric study, treatment planning, and surgical correction (our experience). AB - We have studied and treated 12 selected cases of condylar hyperplasia. All of our cases showed no clinical or instrumental sign of still active hyperplastic growth of the mandibular condyle. The cephalometric studies demonstrated in all cases a pathologic vertical growth of the maxilla interesting the posterior segments on the same side of the hyperplastic condyle. We decided not to perform a condylectomy because we did not expect the condyle to grow any further. The treatment consisted of Le Fort I osteotomies and sagittal split osteotomies sometimes in combination with genioplasty and mandibular remodeling. The mandibular physiologic movements were preserved in all cases. PMID- 2594317 TI - Facial-skeletal manifestations of Engelmann's disease. AB - Engelmann's disease is a hereditary bone disorder that affects the axial and the appendicular skeleton. The facial examination is altered secondary to the progressive osseous changes. This report presents a case of Engelmann's disease in a patient with maxillofacial trauma and reviews the associated facial and skeletal manifestations. PMID- 2594318 TI - The oral cavity as a port of entry for early infections in patients treated with bone marrow transplantation. AB - Before treatment of 181 patients with bone marrow transplantation (BMT) for leukemia, severe aplastic anemia, or metabolic disorders, the oral condition was examined clinically and roentgenologically. Fifty-three patients (29%) had chronic dental infections (osteitis) that needed treatment before BMT. In 10 of 181 cases (6%), BMT was postponed because of oral infections. Septicemia during the neutropenic phase was caused by oral microorganisms (alpha streptococci) in 24 of 59 (41%) patients with microbiologically proven septicemia. Septicemia with alpha streptococci was associated with graft-versus-host disease prophylaxis with methotrexate and subsequent increased frequency of oral ulcerations. No difference was observed in the frequency of reactivation of latent herpes simplex virus infection between different graft-versus-host disease prophylaxis regimens. Reactivation was more frequent in patients conditioned with total body irradiation than in patients conditioned without total body irradiation. Antiviral prophylaxis, with subsequent decreased frequency of oral herpes simplex reactivation, appeared to contribute to a low frequency of septicemia with alpha streptococci. PMID- 2594319 TI - The Rieger anomaly concomitant with multiple dental, craniofacial, and somatic midline anomalies and short stature. AB - An unusual, isolated case of the Rieger anomaly coincident with a multitude of dental, craniofacial, and systemic anomalies is described. Significant dental findings were severe enamel hypoplasia, conical and misshapen teeth, hypodontia, and impactions. Craniofacial disorders were underdevelopment of the maxilla, mandible, and anterior and posterior cranial bases, low-set ears, and a wide nasal bridge. Reported for the first time is the association of this genetic disorder with bilateral microcondyles and bilateral choanal atresia. Embryologic disturbance of the neural crest ectoderm is suspected. The patient also manifested anal atresia, scoliosis, kyphosis, and short stature. A discussion distinguishing this case report from the Rieger syndrome is presented. In addition, the possibility that the patient exhibited a previously unreported syndrome is also considered, and the term Short-F-R-A-M-E is proposed to name this new syndrome. PMID- 2594320 TI - Oral fibromatosis in tuberous sclerosis. AB - Thirty-six families with tuberous sclerosis (TS) were clinically examined for oral fibromatosis and other previously reported oral anomalies. These consisted of 48 affected persons and 69 apparently unaffected parents and children. Fifty control subjects were also examined. Oral fibromatosis was observed in 56% of patients with typical TS and in none of 9 "atypical" cases. The total prevalence was 46%. Similar lesions were not seen in the control series, and they were rare in the otherwise apparently normal relatives with TS. However, three parents of patients with TS were found to have oral fibromas even though they had no signs of TS. It is suggested that examination for oral fibromatosis should be made in all persons suspected of having TS and in their close relatives, since such examination may identify other unsuspected carriers of the gene within the family. PMID- 2594321 TI - Dentin formation in so-called "fibro-osteo-cemental" lesions of the jaw: histologic, electron microscopic, and immunohistochemical investigations. AB - Two cases of the so-called fibro-osteo-cemental lesions of the jaws, containing unusual deposits of hard tissue, are described. There were peculiar spheroid calcifications or larger masses forming small cavities with a radial arrangement and discontinuous blasts extending with axonlike cell processes toward an acellular core. For further definition, electron microscopic and immunohistologic studies were done. The most conspicuous features were abundant intracytoplasmic vimentin filaments in the blasts, tight junctions, matrix vesicle formation, a globular accretion pattern, and so-called matrix maturation. These findings militate against an osseous or cementous nature of this hard tissue. Rather, both the light and electron microscopic findings are highly compatible with the assumption that the blasts are odontoblasts and that an immature type of dentin is formed. In addition to fibroblasts, osteoblasts, and cementoblasts, apparently also a further descendant of the ectomesenchyme--the odontoblasts with dentin formation--may participate in the so-called fibro-osteo-cemental lesions. PMID- 2594322 TI - Familial gigantiform cementoma: classification and presentation of a large pedigree. AB - Very few cases of gigantiform cementoma have been reported, and those associated with a positive family history are especially rare. Confusion exists about the relationship of gigantiform cementoma to florid osseous dysplasia, cementifying fibroma, and diffuse chronic sclerosing osteomyelitis. It has been unclear whether gigantiform cementoma should be accorded the status of a separate entity. In this article, we report our findings on a family that, over five generations, has exhibited clinical, radiographic, and/or histologic findings consistent with the designation familial gigantiform cementoma. This pedigree consists of 55 members. Significant heterogeneity in expression of this trait was noted. The pattern of occurrence of the trait is consistent with an autosomal dominant mode of inheritance with variable expressivity of the phenotype. We suggest that familial gigantiform cementoma should be recognized as a separate entity. PMID- 2594323 TI - Florid osseous dysplasia in Orientals. AB - Florid osseous dysplasia has been described as a condition that characteristically affects the jaws of middle-aged black women. It usually manifests as multiple radiopaque cementum-like masses distributed throughout the jaws. This condition has also been classified by various authors as sclerosing osteomyelitis, sclerosing osteitis, sclerotic cemental masses, gigantiform cementoma, and various other terms. In this series, we want to document eight cases of florid osseous dysplasia in middle-aged, female ethnic Chinese and one case in an Indian subject on the basis of radiographic and histopathologic findings. On the basis of this series, incidence is estimated to be 0.01 case per year 100,000 population. Florid osseous dysplasia constitutes 11% of cemental lesions in our files. PMID- 2594324 TI - Multiple familial ossifying fibromas: relationship to other osseous lesions of the jaws. AB - Multiple familial ossifying fibroma is a very rare jaw lesion. A 31-year-old white woman who had this heritable condition is reported. A differential diagnosis has been discussed to delineate an entity that has not appeared in the previous literature. PMID- 2594325 TI - Bilateral ossifying fibroma of the maxillary sinus. AB - A case involving a 35-year-old man with massive, bilateral, slow-growing ossifying fibromas in the maxillary sinuses resulting in facial deformity and orbital compression is discussed. The historical difficulty in categorizing fibro osseous lesions and the importance of clinical, radiographic, and surgical findings relating to the proper diagnosis and treatment are reviewed. The use of the CT scan to delineate the extent of the pathologic lesion is demonstrated. PMID- 2594326 TI - Temperature changes in thermoplasticized gutta-percha: a comparison of two ultrasonic units. AB - With the use of an extracted human tooth as in vitro model, this study measured temperature changes in the surface of gutta-percha while it was being ultrasonically thermoplasticized. Two sources of ultrasonic oscillation were used: a Cavitron 2001 ultrasonic unit with a file in a PR-30 insert and an ENAC ultrasonic unit with a plugger or file. Temperature elevation in the apical third of the tooth was minimal with either instrument (1.66 degrees C to 3.74 degrees C). The temperature rise in the middle third was higher with the ENAC unit, although probably still within clinically acceptable limits (range, 6.35 degrees C to 19.10 degrees C). The time taken for each unit to thermoplasticize the gutta percha and reach a predetermined distance in the experimental model was recorded and defined as instrument efficiency. The Cavitron unit that had the PR-30 insert with a No. 25 file required 0.48 sec/mm, whereas the ENAC unit with a No. 25 file required 10.83 sec/mm and the ENAC unit with a plugger required 8.38 sec/mm. It appears that the Cavitron unit with a PR-30 insert was more than 22 times as efficient as the ENAC unit for thermoplasticizing gutta-percha under the experimental conditions used in this study. PMID- 2594327 TI - Evaluation of antimicrobial activity in vitro of ten root canal sealers on Streptococcus sanguis and Streptococcus mutans. AB - The antimicrobial activity of ten root canal sealers was studied on Streptococcus sanguis and Streptococcus mutans. One hundred plates of trypticase soy agar-sheep red blood cell (10%), each with four distinct 3 mm diameter wells, were divided into two groups of 50 by means of the Lawn technique; one group was inoculated with S. sanguis and the other with S. mutans. Four milligrams of each root canal sealer was placed in each of three wells in 10 plates (five plates of each inoculant); the fourth well was left empty as a control site. Plates were incubated at 37 degrees C and checked after 2, 7, and 14 days. All root canal sealers inhibited growth of both organisms. The inhibitory zones for S. sanguis were larger than inhibitory zones for S. mutans for all tested sealers, except Diaket. Dentinol, Kerr, and Tubliseal had significantly more inhibitory effect on S. sanguis than did other tested sealers (p less than 0.05). Diaket had superior inhibition on S. mutans. PMID- 2594328 TI - Overfilling of the root. A case report. AB - In this report, attempts have been made to present as an interesting case report overfilling of the root canal, which is one of the most important errors caused by a dentist. The iodoform paste that was applied as a result of canal treatment, which was performed on the left mandibular second premolar, did not only overfill the apical lesion of that tooth but also extended as far as the apical region of the left mandibular second molar. In the periapical and panoramic radiographs, it is seen that the overfilled canal filling material extended as far as the angulus region of the mandible. It is also observed that the canalis mandibularis was not affected by this process and that the overfilled canal paste extended through the trabeculae of the mandibular bone. The fact that the paste disappeared after a short period of time supports the view that the canal filling material was the iodoform paste, which was resorbed. PMID- 2594329 TI - Comparison of x-radiation doses between conventional and rare earth panoramic radiographic techniques. AB - The radiation dose to radiobiologically critical organs at various anatomic sites in a phantom was compared with the use of rare earth screen/film combinations and calcium tungstate screen/film combinations. Rare earth screens and films produced a reduction in dose up to 40% to 50% depending on the anatomic site. PMID- 2594330 TI - Three-dimensional computed tomography and anatomic replicas in surgical treatment planning. Report of a case. AB - A case that demonstrates the use of three-dimensional computed tomography and anatomic replication in the management of a severe anterolateral open bite deformity is presented. Preoperative surgical treatment planning was facilitated by rehearsal model surgery. Construction of an accurate surgical splint enabled precise positioning of osteotomized segments at surgery. PMID- 2594331 TI - Comparative evaluation of the sensitometric properties of screen-film systems and conventional dental receptors for intraoral radiography. AB - This investigation determined the sensitometric properties of 27 rare-earth screen-film combinations and compared them to E- and D-speed films and xeroradiography, the current standards for intraoral radiography. A series of exposures from base plus fog to film saturation were made to determine the Hurter and Driffield curve of each image receptor. The base plus fog, film saturation, speed, gamma, average gradient, and resolution were determined. When dental receptors and screen-film systems are compared on the basis of radiographic quality (contrast and resolution), many screen-film systems have similar resolution (greater than 10 line pairs/mm), significantly greater contrast (greater than 2.0), and a substantial speed advantage (greater than 10). Thus selected screen-film systems may be an alternative to conventional dental receptors for intraoral radiography. PMID- 2594332 TI - Use of three-dimensional computerized tomography in the diagnosis of an obstructed coronoid process. AB - The principles of three-dimensional computerized tomography are discussed. An unusual case of an iatrogenically induced coronoid obstruction is presented with the three-dimensional computerized tomograph as an integral tool in its diagnosis. PMID- 2594333 TI - Symmetric midline mandibular radiolucency. PMID- 2594334 TI - Histogenetic study of the vestibular ganglion in the developing chick embryo by lectin-horseradish peroxidase methods. AB - Hatchery eggs of White Leghorn hens were incubated and the vestibular ganglion cells of 3.5- to 6-day-old chick embryos were studied by the lectin-horseradish peroxidase methods (WGA, UEA-1). In the 3.5-day-old chick embryos, the facial acoustic ganglion mass was recognized close to the otic vesicle. The statoacoustic ganglion reacted to lectins on the rhombencephalic side, indicating that glycoconjugates play a role in the nerve connection between ganglion and rhombencephalon. In the 4-day-old chick embryos, a strong reaction to lectins was observed on the ganglion cell membrane of the geniculate and statoacoustic ganglions, suggesting that glycoconjugates may be related to their differentiation. In 4- and 5-day-old chick embryos, the mesenchymal tissue showed a strong reaction to lectins, suggesting that it plays an important part in the differentiation of the vestibular ganglion. PMID- 2594335 TI - Brainstem auditory evoked response sensitivity: comparison with other neurologic tests in the detection of retrocochlear lesions. AB - Brainstem auditory evoked response (BAER) tests were obtained in 3 patients with suspected retrocochlear lesions. Subsequently, CT scans and the surgical procedure demonstrated tumors of about the same size (2 cm) in the cerebellopontine angle. One was an VIIIth-nerve schwannoma, one a meningioma, and one a VIIth-nerve neuroma. BAER recordings were analyzed with results of other tests: conventional audiometry, stapedius reflex measurements and electronystagmography (ENG). A striking finding was a normal BAER in the patient with the VIIIth-nerve schwannoma. ENG recordings in this case showed ipsilateral impairment of optokinetic nystagmus. The BAER was abnormal in the other 2 patients. A consistent abnormality for the 3 patients was absence of stapedius reflex in the ear in question. This study disclosed the advantage of utilizing a battery of tests in the investigation of retrocochlear lesions. The ENG recordings should include evaluation of the vestibulo-oculomotor pathways. PMID- 2594336 TI - Effect of terbutaline on human eustachian tube function. AB - Terbutaline, a beta 2-adrenoceptor agonist, was administered subcutaneously to 10 healthy adult subjects. The pressure opening level (Pol) of the Eustachian tube (ET) and the remaining middle ear pressure when the ET closed (Pcl) after passive equilibration were measured as well as parameters for active tubal function. A quantitative impedance method in combination with a pressure chamber was used. Pol was reduced by 0.29 +/- 0.10 (-7.3%) kPa 90 min after injection of terbutaline 5 micrograms/kg body weight. There was also a decrease in Pcl, 0.17 +/- 0.06 kPa (-14.0%). No such decrease was seen after saline solution injected subcutaneously. It is suggested that terbutaline facilitates the ET opening by stimulating the secretion of surface tension lowering substances. PMID- 2594337 TI - Mesenchymal chondrosarcoma of the ethmoid sinus. AB - Mesenchymal chondrosarcoma arising from primitive mesenchymal cells is a distinctive type of chondrosarcoma that exists in both skeletal and extraskeletal forms. The tumor is composed of undifferentiated cells with focal areas of cartilaginous or chondroid matrix. An extremely rare case of mesenchymal chondrosarcoma of the anterior and middle ethmoid sinuses in a 16-year-old girl is presented. Magnetic resonance imaging provided more anatomic information about the tumor than computerized tomography and aided in surgical planning. PMID- 2594338 TI - [Prerequisites for the manual therapy of diseases of the cervical spine]. AB - The authors examine the anatomical and biomechanical peculiarities of the upper and lower cervical vertebromotor segments. A differential administration of the manual therapy methods to influence various levels of the cervical spine is substantiated. It has been demonstrated that the mobilization of the atlanto occipital joints should be carried out by means of flexion and extension movements and lateral inclinations. It is supposed that the atlanto-occipital complex of joints may be affected by means of combination of axial traction and rotation of the cervical spine. The manipulations on the lower cervical vertebromotor segments require a combined application of lateral inclinations and rotation. PMID- 2594340 TI - [Stable internal rod fixation of the spine]. PMID- 2594339 TI - [The diagnostic and treatment characteristics of spinal fractures in the victims of multiple trauma]. AB - The authors present their experience in the treatment of 107 patients with spinal injuries associated with polytrauma. The topical diagnosis of the spinal lesions in the severely injured patients was rather difficult both at the preclinical stage and during the clinical examination. For making the diagnosis in combined spinal trauma urgent laparoscopy and aimed roentgenography was employed with the patient in the dorsal position. When the latter technique is employed, a special attachment ("cassette holder") is used which allows to make the roentgenograms with mobile X-ray units. The authors have proposed a new construction of the reclining hammock for the treatment of the patients with the thoracic and lumbar spine traumas associated with severe injuries of the head, the breast and the extremities. It is pointed out that in the patients with complicated spinal injuries the surgical treatment of the locomotor system is most effective. PMID- 2594341 TI - [The diagnostic and treatment characteristics of combined injuries to the spine and chest cavity]. AB - The author has analysed the combined injuries of the spinal column and the chest in 46 (2.19%) patients. In the treatment of the spinal injuries conservative (combined and functional) and surgical (in the posterior and in the anterior compartments) methods were employed differentially which allowed to reduce the period of treatment of the patients and to restore the working capacity. PMID- 2594342 TI - [Changes in the parameters of external respiration in patients with Bechterew's disease treated by hyperbaric oxygenation]. AB - The method of hyperbaric oxygenation (HBO) has been used in the treatment of the patients with Bechterew's disease at the Clinic of Traumatology, Orthopaedics and Field Surgery of the Kuibyshev Medical Institute since 1980. The changes in the values of the external respiration function in 111 patients have been studied. After 20 HBO procedures there has been a normalization of the most values of external respiration. PMID- 2594343 TI - [Experimental data on the morphogenesis of the spinal compression syndrome in congenital scoliosis]. AB - The authors have made a roentgenologic and histologic study of the preparations of the vertebral columns of 13 rats with congenital scoliosis born to the rats who had been administered a teratogenic drug (6-merkaptopurin) during their pregnancy. In part of the rats the spinal deformations were accompanied by pathologic changes in the vertebrae and in the discs and by an abrupt narrowing (flattening) of the vertebral canal which caused disturbance in the blood flow in the mater spinalis, edema and sclerosis of the epidural space, hypoxia of the neurons, atrophy and glial and cicatrix substitution of the spinal cord tissue in the area of the curvature. The observed clinical picture of the compression spinal syndrome (posterior paraparesis with disturbed functions of the organs of the pelvis) reminded of similar disturbances in the patients with severe congenital kyphoscoliosis. PMID- 2594345 TI - [Manual therapy in the combined treatment of spinal osteochondrosis]. AB - The article reflects the experience in the work of the manual therapy consulting room at the Smela town hospital named after N. A. Semashko in Chernigov Province from November 1985 to December 1987 inclusive. The author presents the results of treatment of 906 outpatients. The optimal number of the manual therapy procedures during the first course was six. The procedures took place every other day. Manual therapy was administered together with massage, exercise therapy, electrophysical procedures, traction and fixation elements. The results of the treatment were good in 85.8%, satisfactory in 11.5% and bad in 2.7% of the cases. PMID- 2594344 TI - [Assessment of the prophylactic activity of staphylococcal anatoxin and Proteus vaccine in the combined treatment of patients with trauma to the locomotor system]. PMID- 2594346 TI - [Clinico-thermographic characteristics of humeroscapular periarthritis in cervical osteochondrosis]. PMID- 2594347 TI - [The longitudinal arch of the foot in children with scoliosis]. PMID- 2594348 TI - [Osteosyndesmolysis of the body of the sternum in a child]. PMID- 2594349 TI - [Methods for spinal fixation]. PMID- 2594350 TI - [New devices for the surgical treatment of scoliosis patients]. PMID- 2594351 TI - [A device for unstressing of the lumbar spine]. PMID- 2594352 TI - [Determination of the maximum time period for temporary work incapacity in trauma patients]. PMID- 2594353 TI - [The status and measures for the improvement of the training of traumatologists and orthopedists in the Ukrainian SSR]. PMID- 2594354 TI - [Problems in setting work standards for the medical personnel of microsurgery departments]. PMID- 2594355 TI - [Variations of unstable spinal injuries]. PMID- 2594356 TI - [The concept of traumatic disease today]. PMID- 2594358 TI - [The prediction of results...posttraumatic/traumatic osteomyelitis]. PMID- 2594357 TI - [The functional treatment of diaphyseal fractures of the femur]. PMID- 2594360 TI - Abstracts issue. 1989 ISSOL meeting. Prague, Czechoslovakia. PMID- 2594359 TI - [The surgical treatment of dislocations and fracture-dislocations of cervical vertebrae 3-7]. AB - The authors have analysed the results of the treatment of 131 patients with dislocations and dislocation fractures of C 3-7. The stabilization of the injured segment by posterior surgical approach with a fixative draw was performed in 64 cases of dislocations of the cervical vertebrae when the compression of the spinal cord and its roots was eliminated by the setting of the dislocation. Anterior compression of the dural sac and disturbances in the supportability of the spinal column was an indication for anterior decompression and corporodesis in 67 cases. PMID- 2594361 TI - [Giant secondary vaginal calculus]. AB - The development of a large vaginal stone in a 25-year-old female, correlated with vesicovaginal fistula, is presented. The stone, composited of struvite and carbonate apatite, formed around non-absorbable surgical suturing material in urine with urease producing (P. mirabilis) bacterial infection. The stone was removed by simple lithotripsy technique. Attention is taken for the importance of stone prevention. PMID- 2594363 TI - [Daily routine of nurses--rehabilitation of the nursing profession]. PMID- 2594362 TI - [Nursing education in Austria]. PMID- 2594364 TI - [Survey of home nursing at the Austrian Red Cross]. PMID- 2594365 TI - [The hospital as a hotel? The value of the hotel service and leisure time for patient satisfaction]. PMID- 2594366 TI - [Patient-oriented self-experience groups]. PMID- 2594367 TI - The putative oncogene Spi-1: murine chromosomal localization and transcriptional activation in murine acute erythroleukemias. AB - We have shown previously that spleen focus forming virus integration near the Spi 1 putative oncogene is observed in 95% of erythroid Friend tumors (Moreau Gachelin et al., 1988). Here we describe how the proviral insertion in the Spi-1 domain is associated with the enhanced transcription of a 1.4 kb mRNA normally expressed at a low level in normal cells. The gene is localized on murine chromosome 2, band E3. The structure of the Spi-1 gene was determined by sequencing genomic and cDNA clones. The gene has an open reading frame encoding a protein of 218 amino acids, extending over five exons. Proviruses always integrate outside, upstream and in the opposite orientation of the protein encoding domain. This suggests that SFFV integration activates the expression of Spi-2 gene that may contribute to the erythroleukemic process. PMID- 2594368 TI - High frequency of activation of tyrosine kinase oncogenes in human papillary thyroid carcinoma. AB - We had previously detected a transforming oncogene, designated PTC, in 25% of 20 papillary thyroid carcinomas. In order to characterize further the transforming activity of this tumour histotype, a new panel of tumour specimens from 16 patients was analysed by using a modified calcium phosphate-DNA coprecipitation transfection protocol. Tumour DNA from 10 patients (62%) displayed a transforming activity due to activation of three different oncogenes identified in four cases as PTC, in four cases as TRK, and in two cases as N-RAS. The same structural alterations of PTC and TRK (gene rearrangements) as well as of N-RAS (point mutation) detected in the NIH3T3 transformants, were also found in the original tumour DNAs, thus indicating that their activation was not due to transfection procedures. Since both PTC, a novel rearranged form of RET, and TRK display a tyrosine protein kinase activity, it is proposed that the activation of this class of oncogenes is specifically involved in the pathogenesis of papillary thyroid cancer. PMID- 2594369 TI - Detection of human immunodeficiency virus (HIV) and human lymphotropic virus (HTLV) type I or II dual infections by polymerase chain reaction. AB - To type the specific human T-lymphotropic virus (HTLV) coinfection in acquired immunodeficiency syndrome (AIDS) patients, we have utilized the polymerase chain reaction technique. The primer pairs employed for HTLV-I and HTLV-II are derived from pol and env regions and gag region for human immunodeficiency virus (HIV). The data indicate that the selected primer pairs are specific for each virus and are able to detect HTLV-I and -II coinfection in lymphoid cells established from AIDS patients. PMID- 2594370 TI - Papers presented at the conference 'Advances in the assessment of visual function and structure'. London, 7-8 July 1988. Abstracts. PMID- 2594371 TI - The subjective assessment of cataract. AB - The medical treatment of cataract now appears to be a distinct possibility. A number of anti-cataract formulations are being clinically tested, and more clinical trials are being planned. To obtain a true assessment of a drug's efficacy, a battery of tests are needed which can accurately assess cataract progress. A clinical trial of the proposed anti-cataract drug Bendalina is being conducted. The six subjective methods used to assess cataract progression in the trial are presented. These are refractive error, LogMAR visual acuity, contrast sensitivity, glare sensitivity, retinal visual acuity and displacement threshold hyperacuity. The reasons for using each technique and their method of measurement is explained. PMID- 2594373 TI - Contrast sensitivity and glare sensitivity changes with three types of cataract morphology: are these techniques necessary in a clinical evaluation of cataract? AB - LogMAR visual acuity, contrast sensitivity and glare sensitivity measurements were made on 39 eyes of 18 cataractous subjects and compared against normative data. Only cataracts of one of the main three morphological cataract types were used--cortical, nuclear and posterior subcapsular. Results indicate that contrast sensitivity decline with cataract is an intermediate and high spatial frequency loss. For nuclear and cortical cataracts with a LogMAR visual acuity of less than 0.5 (Snellen equivalent better than 6/18), there was no loss of contrast sensitivity at the lowest spatial frequency (1 c/deg). For posterior subcapsular cataracts, low spatial frequency contrast sensitivity loss did occur but was unrelated to visual acuity. Glare sensitivity increased for all cataract types. This was related to visual acuity for both cortical and nuclear cataracts but was not for the posterior subcapsular type. It was concluded that contrast and glare sensitivity measurements are a useful part of the assessment of visual function in patients with posterior subcapsular cataract. PMID- 2594372 TI - Prediction of visual function behind cataract using displacement threshold hyperacuity. AB - Visual acuity and displacement threshold hyperacuity were measured in a group of patients awaiting cataract extraction, and this was repeated several weeks subsequent to surgery. In addition, measurements were made on a group of patients with various ocular pathologies but without the presence of cataract. Displacement thresholds in the cataract group increased only slightly with the severity of the opacity. On the other hand, displacement thresholds for the pathology group showed a marked dependence upon visual acuity--the worse the acuity, the higher the threshold. This results in a clear distinction between vision loss due to optical factors (cataract) and retinal/neural factors. There was a good correlation between pre- and post-operative displacement thresholds in the cataract group, with post-operative thresholds being slightly better than pre operative thresholds. The results suggest that this technique may offer patients a good indication of the likely quality of vision achieved following cataract extraction. PMID- 2594374 TI - Referrals and notifications by optometrists within the UK: 1988 survey. AB - In a survey of nearly 75,000 eye examinations, 6% of patients were referred to a medical doctor and the doctor was notified in a further 2% of cases. The level of referral was 2% higher than in 1986; 70% of referrals were the result of reminders or periodic attendances, and 80% of those referred were over 40 years of age. The general pattern of referral was broadly in agreement with a survey conducted in 1986 but indicates that some categories of eye conditions are being referred at a higher rate. PMID- 2594375 TI - Crystalline lens accommodation and anterior chamber depth. AB - Using paraxial equations, the change in dioptric power of the crystalline lens required to image objects at given distances from the eye, on the retina, is calculated. This shows that the depth of the anterior chamber affects crystalline lens accommodation more than other variables. The relationship between anterior chamber depth and presbyopia, and a possible geographical aspect, are discussed. PMID- 2594376 TI - The effects of 0.025% hyoscine hydrobromide eyedrops on visual function in man. AB - Instillation of three drops of 0.025% hyoscine hydrobromide into one eye at 5 min intervals caused a mydriasis and cycloplegia of rapid onset and of 4-6 days' duration; this was similar to the previously reported actions of concentrations of up to 0.5%. After refraction for the working distance of the experiments, contrast sensitivity to stationary oscilloscope-generated grating patterns of 10 and 20 c/deg was unaffected despite the mydriasis. Also, contrast sensitivity to laser interference fringes of 10 and 20 c/deg observed in the Maxwellian view, in which the effects of the ocular media are bypassed, was unaffected. Contrast sensitivity to a 3 c/deg phase-reversed grating pattern was, however, transiently reduced by 40% after hyoscine. A second series of experiments showed a deleterious effect of hyoscine on contrast sensitivity to both stationary and phase-reversed grating patterns of 2, 3 and 5 c/deg while contrast sensitivity at 10 c/deg was not consistently affected. These results were explained by a direct deleterious action of hyoscine at the level of the retina, specific to channels that detect low spatial frequencies. PMID- 2594377 TI - The effect of spatial frequency on binocular contrast inhibition. AB - Previous work has shown that binocular contrast summation, obtained with equal monocular sensitivities, remains constant over a range of spatial frequencies. We measured binocular contrast detection with a log 1.00 ND filter placed in front of one eye. For all eight subjects, the binocular contrast detection decreased to a level below that of the monocular detection, demonstrating a contrast analogy to Fechner's paradox. The degree of binocular inhibition, like summation, remained constant across the range of spatial frequencies. PMID- 2594378 TI - Computed extraocular muscle activity during blinks. AB - The rotations and retractions of the eyeball due to co-contraction of the extraocular muscles are investigated using a model of the mechanics of the orbital plant. The hypothesis that the rotational movements are secondary to globe retraction is not supported. PMID- 2594379 TI - Reflection characteristics of the human fovea assessed by reflecto-modulometry. AB - The optical quality of the human fovea was assessed by measuring the modulation of aerial fringes conjugate with the retina. The different possible causes of the decrease in modulation of this pattern were successively investigated, the main one being the passage through outer segments in unguided modes. Modulation diagrams measured on the fovea were compared with those of the perifovea. PMID- 2594380 TI - Optical matrices of lenticular polyindicial schematic eyes. AB - The optical matrices for modified schematic eyes are derived. The primary modification is to replace the usual isoindicial or bi-indicial crystalline lens with a polyindicial lens so as to more closely approximate the living human lens. Further modifications are made to simulate the accommodated state. The use of optical matrices to solve an optometric problem is demonstrated. PMID- 2594381 TI - The bandage lens in bullous keratopathy. AB - One of the most common indications for the fitting of therapeutic contact lenses is bullous keratopathy, a painful condition often iatrogenic in origin and more usually encountered in elderly patients. A retrospective study of 30 patients fitted with therapeutic lenses for the condition and followed up for at least a year showed that the symptoms of bullous keratopathy were reduced in most cases. There was a higher incidence of suppurative keratitis (13 per cent) than has been reported in previous series. The prescribing of prophylactic antibiotics was haphazard in the series, and the authors suggest further study is needed to determine their precise role. PMID- 2594382 TI - An evaluation of Bennett's method for determining the equivalent powers of the eye and its crystalline lens without resort to phakometry. AB - Refraction and optical components have been measured in 36 eyes using objective optometry, keratometry, ophthalmophakometry and A-scan ultrasonography. A computing scheme was used to confirm that the accumulated experimental errors for a phakometric technique tend to exceed the inherent errors of a new method which calculates the equivalent powers of the eye and its crystalline lens without resort to phakometry. Bennett's method was shown to be a valuable technique in biometric studies which obviates the need for lengthy experimental investigations. PMID- 2594383 TI - The measurement of adaptation of tonic accommodation under two open-loop conditions. AB - Pre- and post-task tonic accommodation (TA) was measured using an objective infra red optometer under two open-loop conditions: a darkroom and a bright empty-field (60 cd m-2). The task was of 10 minutes' duration and was located at -1, -3 and 5 D. Post-task TA was measured immediately after the task and over a period of 90 s. Mean data for the group of 10 young men subjects showed that the open-loop condition adopted had no significant influence on the post-task regression patterns of TA towards pre-task values. Three subjects did, however, show significantly more sustained increases in post-task TA for the bright-field condition; one markedly so. Conversely, two subjects showed more pronounced post task shifts for the darkroom condition. PMID- 2594384 TI - Accommodative fluctuations in Adie's syndrome. AB - Recent reports suggest that the higher frequency components (around 2 Hz) of accommodative fluctuations may arise from the accommodative 'plant' and may have no role in the control of the accommodation system. The dynamic responses of accommodation in two cases with Adie's syndrome were recorded. The results showed that the velocity of accommodative responses was reduced, and the accommodative fluctuations in the higher frequency components were completely diminished. It can be concluded that the origin of fast fluctuations is not located at a more peripheral site than the lesion of tonic accommodation. Since the possible lesion exists at the ciliary ganglion, the origin of the fast oscillation may not be the accommodative 'plant', but the neural one. PMID- 2594385 TI - Assessment of toroidal surfaces by the measurement of curvature in three fixed meridians. AB - A method is described where the surface curvatures and axis orientation of a toroidal surface can be determined by measuring the lens in three fixed orientations. This method also has possible applications in the measurement of progressive addition lenses. PMID- 2594386 TI - A comparison of three methods for the measurement of progressive addition lenses. AB - Three methods of measuring aberrational astigmatism in progressive addition spectacle lenses are described. Measurements are presented from each method made on an Essilor Varilux 2 lens, which illustrate the small differences between the methods for low power lenses. PMID- 2594387 TI - Spherical lens decentration errors by Prentice's rule. AB - Sources and magnitude of errors in applying Prentice's rule in calculating decentration for spherical lenses were investigated. It was found that spherical aberration can be the only source of error in applying the rule. The overall magnitude of errors in effective prismatic effect is, however, clinically insignificant. PMID- 2594388 TI - Light on the peripheral retina. PMID- 2594389 TI - Squaring the refractive power matrix, the equivalent of squaring the sphero cylinder? PMID- 2594391 TI - Papers presented at the meeting of the Society for Experimental Optometry. Birmingham, 25-26 July 1988. Abstracts. PMID- 2594390 TI - The effect of vergence adaptation on convergent accommodation. PMID- 2594392 TI - Post-herpetic neuralgia: the relation of pain complaint, sensory disturbance, and skin temperature. AB - Twelve otherwise healthy patients with longstanding postherpetic neuralgia (PHN) were prospectively studied using clinical examination, infrared thermography and response to local anesthetic skin infiltration. All had at least 2 of 3 possible components to their PHN pain: continuous, neuralgic, or allodynic. In patients with allodynia, maximal reported pain and the location of maximal allodynia on sensory examination were largely overlapping and were often warm thermographically. Areas of dense sensory loss and skin scarring without allodynia were usually cool thermographically. Local anesthetic skin infiltration produced substantial pain relief in all 9 patients (essentially complete relief in 7) with allodynia: the 3 patients with predominantly continuous pain were not relieved. In 7 of 8 skin infiltration responders, the same dose of lidocaine i.m. in the deltoid muscle also produced significant, though less complete pain relief. These results suggest that PHN patients can be divided into at least 2 clinical groups: those with predominantly continuous pain localized to a region of significant sensory loss and those in whom allodynia is the most prominent sensory disturbance. The latter group has pain localized to areas with relatively preserved sensation. The differences in clinical features and response to lidocaine suggest that there are at least 2 different mechanisms contributing to the pain of PHN. PMID- 2594393 TI - Nociceptive flexion reflexes during analgesic neurostimulation in man. AB - Nociceptive flexion reflexes of the lower limbs (RIII responses) have been studied in 21 patients undergoing either epidural (DCS, n = 16) or transcutaneous (TENS, n = 5) analgesic neurostimulation (AN) for chronic intractable pain. Flexion reflex RIII was depressed or suppressed by AN in 11 patients (52.4%), while no modification was observed in 9 cases and a paradoxical increase during AN was evidenced in 1 case. In all but 2 patients, RIII changes were rapidly reversible after AN interruption. RIII depression was significantly associated with subjective pain relief, as assessed by conventional self-rating; moreover, in 2 patients it was possible to ameliorate the pain-suppressing effects of AN by selecting those stimulation parameters (intensity and frequency) that maximally depressed nociceptive reflex RIII. We recorded 2 cases of RIII attenuation after contralateral neurostimulation. AN appeared to affect nociceptive reflexes rather selectively, with no or very little effect on other cutaneous, non-nociceptive responses. Recording of RIII reflexes is relatively simple to implement as a routine paraclinical procedure. It facilitates the objective assessment of AN efficacy and may help to choose the most appropriate parameters of neurostimulation. In addition, RIII behavior in patients could be relevant to the understanding of some of the mechanisms involved in AN-induced pain relief. PMID- 2594394 TI - Pressure pain thresholds, clinical assessment, and differential diagnosis: reliability and validity in patients with myogenic pain. AB - Four studies are presented testing the validity and reliability of pressure pain thresholds (PPTs) and of examination parameters believed to be important in the clinical assessment of sites commonly used for such measures in patient samples. Forty-five patients with a myogenous temporomandibular disorder were examined clinically prior to PPT measures. Criteria for history and examination included functional aspects of the pain, tissue quality of the pain site, and the type of pain elicited from palpation. Control sites within the same muscle and in the contralateral muscle were also examined. PPTs were measured as an index of tenderness using a strain gauge algometer at these sites. The data from the 5 male subjects were excluded from subsequent analyses due to the higher PPT in the males and to their unequal distribution among the various factorial conditions. The first study demonstrated strong validity in PPT measures between patients (using pain sites replicating the patients' pain) and matched controls (n = 11). The PPT was not significantly different between the primary pain site (referred pain and non-referred pain collapsed) and the no-pain control site in the same muscle (n = 16). The PPT was significantly lower at the pain site compared to the no-pain control site in the contralateral muscle (n = 13). The second study indicated adequate reliability in patient samples of the PPT measures. In the third study, the PPT was significantly lower at sites producing referred pain on palpation compared to sites producing localized pain on palpation. The PPT findings from the control sites were inconsistent on this factor. The fourth study presented preliminary evidence that palpable bands and nodular areas in muscle were most commonly associated with muscle regions that produce pain; such muscle findings were not specific, however, for regions that produce pain. Further, the intraexaminer reliability in reassessing these pain sites qualitatively was only fair. Referred pain had a poor association with the pain pattern and physical findings, which may suggest a need to reevaluate part of the theory regarding referred muscle pain. The reliability of PPT measures was better overall than the reliability of the signs and site-specific symptoms, suggesting that pressure pain thresholds may be an important tool in clinical studies of pain. PPT measures demonstrate a high within-subject variability in pain patient subjects as well as non-pain subjects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2594395 TI - Diagnostic epidural opioid blockade in primary fibromyalgia at rest and during exercise. AB - Nine patients with primary fibromyalgia participated. The patients were studied prior to, during and immediately after 4 identical periods of exercise (bicycle ergometer) each performed 30 min after injection with saline, repeated saline, an opioid and naloxone. All substances were given epidurally, except for naloxone which was given intravenously. Finally, with the patients resting in bed, lignocaine was injected epidurally. Physiological variables, general exertion, dyspnoea, lower extremity exhaustion, pain and tender points in the lower half of the body were examined. Resting pain and tender points diminished significantly after the opioid injection. Lignocaine completely abolished resting pain and tender points. Lower extremity exhaustion was reduced by the opioid. General exertion and dyspnoea were unaffected by the opioid. In conclusion the results support the hypothesis that the pain in fibromyalgia is of peripheral nociceptive or spinal origin. We raise the hypothesis that the fatigability is, at least partly, due to inhibition because of pain. PMID- 2594396 TI - Cross-tolerance between systemic and epidural morphine in cancer patients. AB - Cross-tolerance to epidural morphine after prior systemic morphine therapy was studied in 26 cancer patients treated for relief of pain secondary to metastatic disease. A 'tolerance index' was calculated for each patient by multiplying the duration of previous morphine therapy with the daily dose just prior to the study and then compared with changes in the following variables measured after epidural morphine administration: with pain scores on a scale from 0 (no pain) to 10 (maximal pain), heart rate, blood pressure, respiratory rate and minute volume, arterial blood gas tensions of oxygen and carbon dioxide and arterial pH. There was no significant analgesic cross-tolerance to epidural morphine, but clear evidence for cross-tolerance regarding morphine's respiratory depressant action. The duration of the previous morphine therapy exerted a greater influence on the development of ventilatory cross-tolerance than the dose. PMID- 2594398 TI - Cervicogenic, hemicranial attacks associated with vascular irritation or compression of the cervical nerve root C2. Clinical manifestations and morphological findings. AB - Sixteen patients suffering from hemicranial attacks are reported. After many years of unsuccessful conservative treatment (mean = 12.4 years), the patients were treated surgically with good results. The radiological or electrophysiological examinations were non-specific or negative. Only vasoactive tests (provoking or relieving pain) or local anesthesia proved helpful in diagnosing and localizing the origin of pain. Intraoperatively, hemicranial attacks were found to be caused by vascular irritation or compression of the cervical nerve root C2. After decompression (n = 6) or dissection (n = 10) of the nerve root and the ganglion, 12 patients were relieved of their pain, 2 had improved relatively, 1 showed only a slight improvement, and in 1 patient no cause was found and no improvement was achieved. Two patients suffered recurrence of pain postoperatively; one had no further complaints after root extirpation following percutaneous thermorhizotomy. Electron microscopic examination of the nerve root and its ganglion revealed focal morphological changes, including proliferation of connective tissue in the endoneurium and the ganglion itself, the formation of onion-bulb-like structures around single axons, discrete signs of myelin damage and axonal degeneration. These morphological changes are possibly the result of a chronic vascular compression. PMID- 2594399 TI - Analgesia produced by injection of lidocaine into the anterior cingulum bundle of the rat. AB - The role of cingulum in the perception of tonic and phasic pain was examined by injecting lidocaine, a local anesthetic, into the anterior cingulum bundle of the rat. A cannula was stereotaxically implanted into the anterior cingulum on one side in anesthetized rats. Seven to 10 days after surgery, the rats were infused with 1 microliter of 2% lidocaine in saline or saline alone into the anterior cingulum bundle immediately prior to testing for analgesia in the formalin or foot-flick test. Injection of lidocaine into the anterior cingulum bundle produced a significant reduction in formalin pain scores, but had no effect on foot-flick latencies. The analgesia in the formalin test persisted for the entire 40 min observation period. No analgesia in the formalin test was observed in rats that received injections of saline into the cingulum, lidocaine into the cingulum 90 min prior to testing or lidocaine into the cingulate cortex. These data suggest that the cingulum is involved in the perception of tonic pain but not phasic pain, and support previous studies which indicate that different neural mechanisms underlie different types of pain. Furthermore, these findings suggest that the cingulum is involved in the affective component of pain and that interruption of cingulum activity with lidocaine can produce analgesia. PMID- 2594397 TI - The prevalence and impact of pain after day-care tubal ligation surgery. AB - Empirical data from controlled studies using standardized, reliable measures on the amount and quality of pain after laparoscopic tubal ligation and the consequences of this pain on the activities of daily living are extremely scarce. In a study of 54 women admitted to a day-care unit for this procedure, validated measures were utilized to assess the incidence, intensity and duration of pain after tubal ligation (McGill Pain Questionnaire) and the impact of pain on the activities of daily living (Modified Functional Assessment Inventory). Psychological measures (Brief Symptom Inventory, Kranz Health Opinion Survey, and the State-Trait Anxiety Inventory) were employed to test their use as possible predictors for pain, analgesic usage and the time taken to resume a normal activity level after tubal ligation surgery. The results showed that pain is a significant problem after tubal ligation although pain rating scores over the 7 day study period were lower than those reported after major abdominal surgery. Eighty-five percent of our sample reported that pain and/or fatigue impacted on their recovery and contributed to an average delay of return to normal activity level of 4.4 days, not including the day of surgery. The psychological measures did not prove to be strong predictors of postoperative pain, time of return to normal activity level or analgesic usage. The most powerful predictor of return to normal activity was the total amount of pain experienced, as measured by the McGill Pain Questionnaire, during the 7 day post-operative period. PMID- 2594400 TI - Medullary on- and off-cell responses precede both segmental and thalamic responses to tail heating. AB - Medullary on- and off-cell responses to tail heating were studied in lightly anesthetized rats. In 10 animals the electromyographic (EMG) activation of tail muscles was recorded simultaneously with on- or off-cells. The on-cell burst or the off-cell pause always preceded segmental EMG activation by about 0.5 sec. In turn, EMG activation preceded visible tail flick by about 0.09 sec. In 13 other animals ventrobasal thalamic unitary responses were recorded simultaneously with on- and off-cell responses. On-cell bursts or off-cell pauses always preceded thalamic responses by about 0.4 sec. These results support the notion that on- and off-cells play a regulatory role in both segmental and ascending nociceptive transmission. PMID- 2594401 TI - Analgesic effects of different frequencies of transcutaneous electrical nerve stimulation on cold-induced pain in normal subjects. AB - The efficacy of transcutaneous electrical nerve stimulation (TENS) in producing analgesia in cold-induced pain was assessed using a range of 5 stimulating frequencies (10 Hz, 20 Hz, 40 Hz, 80 Hz and 160 Hz) in 83 normal healthy subjects. TENS significantly elevated ice pain threshold when compared with sham and control groups. TENS frequencies between 20 and 80 Hz produced greatest analgesia, while frequencies below and above this level (10 Hz and 160 Hz), although significantly elevating ice pain threshold, produced effects of a lesser magnitude. The frequency of pulse delivery was the governing factor as no significant differences in stimulus intensity were observed across the treatment groups. Measurement of ice pain tolerance was found to be unreliable under the present conditions. No significant relationships were observed between personality variables as measured by Eysenck Personality Questionnaires and the degree of TENS response. PMID- 2594402 TI - The C-fibre conduction block caused by capsaicin on rat vagus nerve in vitro. AB - Capsaicin (0.01-50 microM) was applied to adult rat vagus nerve in vitro to examine the C-fibre conduction block and to compare its time course with that of the depolarisation caused by this drug. The conduction block was assessed by the reduction in the C-wave of the compound action potential. Capsaicin caused a dose dependent decrease in the height and area under the C-wave; the threshold dose was between 0.01 and 0.3 microM and maximum C-wave reduction of about 85% occurred with doses of 5 microM or above. The C-wave reduction was divided into reversible and irreversible components which differed in dose dependency. The threshold for the reversible block was below 0.3 microM and for the irreversible block it was about 1 microM. The onset of the block took about 5 min. regardless of dose. Where there was more than 50% recovery after the block the reversible component was measured. This was dose dependent and its duration was 10-90 min. Removal of external calcium did not affect the magnitude of the C-wave block, although it did seem to prevent recovery of the C-wave. PMID- 2594403 TI - Nociceptive nerve pain and neuropathic pain. PMID- 2594404 TI - Myofascial pain. PMID- 2594405 TI - Magnetic resonance imaging in the assessment of revascularization in Kienbock's disease. A preliminary report. AB - A 25-year-old man with stage II Kienbock's disease of his left lunate underwent an initial period of immobilization. He was subsequently treated by ulnar lengthening, with a good outcome. Magnetic resonance imaging (MRI) was utilized to demonstrate the lack of improvement with cast immobilization and the revascularization that followed surgical treatment. This new application of MRI in cases of avascular necrosis of the lunate may be helpful in the early identification of revascularization. PMID- 2594406 TI - Occult osteomyelitis of the femoral head. A case of unrecognized infection in an anesthetic hip. AB - Unrecognized infection in a bone can lead to a pathological fracture. An example of osteomyelitis of the femoral head followed by a subcapital fracture is described in a patient who was anesthetic below the L1 sensory level. PMID- 2594407 TI - The biomechanics of screws. AB - Screws are simple machines, commonly used in orthopaedics. Understanding the mechanics by which a screw generates compression can facilitate screw selection and insertion techniques and help reduce failure rates. Screw strength depends on both the material and size of the screw. A screw's holding strength depends both on it's type and size and on the type of bone into which it is inserted. Other factors being equal, a larger screw will have greater holding strength than a smaller screw. Properly placed lag screws greatly increase fracture stability and lead to better fracture healing. PMID- 2594408 TI - Aneurysmal bone cyst of the fifth metacarpal. AB - An aneurysmal bone cyst of the hand occurred in a 10-year-old girl. The hand is an extremely rare location for this lesion. A case report is presented along with a review of the medical literature. PMID- 2594409 TI - Tips of the trade #19. An intraoperative technique for measuring compartmental pressures. AB - A useful technique is described for measuring compartmental pressures. Readily available standard operating room anesthesia equipment can be used to obtain accurate, easily reproducible measurements. PMID- 2594410 TI - Invasion of mature and immature erythrocytes of CBA/Ca mice by a cloned line of Plasmodium chabaudi chabaudi. AB - During the early stages of the primary Plasmodium chabaudi chabaudi AS parasitaemia in CBA/Ca mice this parasite invaded normocytes, but as the parasitaemia developed increasing numbers of parasites were seen within reticulocytes. During and just after peak parasitaemia, as further parasite replication was controlled, the 'crisis' phase ensued, mice became increasingly anaemic and reticulocyte numbers were markedly increased. As the parasitaemia was resolved during crisis in excess of 25% of parasites had invaded reticulocytes. In phenylhydrazine-pretreated mice with artificially high reticulocyte levels and infected with P.c. chabaudi AS, normocyte/reticulocyte invasion occurred with equal frequency. No reduction in the infectivity of parasite populations developing in reticulocytes was observed. PMID- 2594411 TI - Characterization of coccidial proteins by two-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis. AB - Two dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (2D SDS-PAGE) has been used to produce 'fingerprint' maps of the proteins from each of the 7 species of Eimeria which infect the chicken. All 7 species could be identified from their array of polypeptides but few differences were detected between strains of the same species. Alterations to the polypeptide array associated with the stage of sporulation of the oocysts were observed. Iodination of sporozoites, 2D SDS-PAGE, autoradiography and immunoblotting techniques were combined to identify polypeptides with a surface moiety and those which were antigenic. PMID- 2594413 TI - Hybrids between Schistosoma mansoni and S. rodhaini: characterization by cercarial emergence rhythms. AB - Hybridization between Schistosoma mansoni, with a diurnal cercarial emergence rhythm and S. rodhaini, with a nocturnal cercarial shedding pattern leads to F1 and F2 generations, hybrid schistosomes whose chronobiological phenotype of cercariae is characterized by two unequal emergence peaks, one diurnal and the other nocturnal. The relative importance of diurnal and nocturnal peaks depends upon which S. mansoni strain (early or late) is used for the hybridization with S. rodhaini. The results are compared and discussed with those resulting from crosses between intraspecific sympatric and allopatric chronobiological variants (early and late) of S. mansoni. The genetic determinism of the cercarial emergence of schistosomes and the significant differences observed between cercarial shedding patterns of parental species and their hybrids allow the use of this behavioural marker in biological and genetical studies in schistosome populations. PMID- 2594412 TI - Use of two-colour flow cytometry to assess killing of Giardia muris trophozoites by antibody and complement. AB - A two-colour flow cytometry technique was used to assess killing of Giardia muris trophozoites by rabbit anti-trophozoite antibodies and complement. Binding of rabbit antibody to trophozoites and killing of trophozoites were documented by flow cytometry, after incubating the organisms with fluorescein-conjugated anti rabbit IgG and propidium iodide (PI). Percentages of PI+ (dead) trophozoites ranged from greater than 80%, after incubation with rabbit antiserum and complement, to less than 30%, after incubation with complement alone. The assay technique may be applicable to studies aimed at determining whether intestinal antibodies from Giardia-infected mammals can kill Giardia trophozoites. PMID- 2594414 TI - Origin, kinetics of circulation and fate in vivo of the major excretory-secretory product of Acanthocheilonema viteae. AB - The excretions-secretions (E-S) of Acanthocheilonema viteae consist mainly of one product, molecular weight 62kDa. This molecule is synthesized during the vertebrate phase of the parasite life-cycle and is first detectable in the E-S of L4 parasites. It is cross-reactive with E-S of human filarial parasites as a consequence of possessing a phosphorylcholine (PC) moiety. The 62 kDa molecule has been employed as a model for the study of the origin and fate of filarial E S. Immunohistological analysis has shown the molecule to be located predominantly in the parasite gut. Transplantation of adult female [35S] methionine pulsed worms into uninfected jirds resulted in the radio-labelled secreted 62 kDa antigen being detected in the bloodstream within 4 h by SDS PAGE/immunoprecipitation analysis. The systemic half-life of the molecule as estimated by clearance of injected, purified 125I-labelled material was measured in naive and infected jird hosts. It was reduced from 2-7 h in naive animals to less than 30 min in 4-10 week infected rodents, a finding which correlated with clearance of antigen by antibody in the infected group. In animals infected for longer time periods the serum half-life returned to the values observed in naive jirds. The idea that this change in half-life may reflect differences in the nature of 62 kDa antigen containing circulating immune complexes as infection progresses is discussed. The 125I-labelled antigen is predominantly removed from the circulation via the liver and ultimately excreted in the urine in a non antigenic form. This work provides the first description of the origin, kinetics of circulation and fate of a defined filarial E-S product and may aid in determining the function and assessing the diagnostic utility of PC-bearing E-S components. PMID- 2594415 TI - The effects of cholinergic and serotoninergic drugs on motility in vitro of Haplometra cylindracea (Trematoda: Digenea). AB - The spontaneous activity of the somatic muscle of the amphibian lung fluke, Haplometra cylindracea has been recorded in vitro, using an isometric force transducer system. Normal movement consisted of a continuous series of regular contractions which were maintained for over 4 h. Acetylcholine (ACh) inhibited motility at a concentration of 1 X 10(-3)M induced a flaccid paralysis. A similar response occurred with the cholinomimetric drugs, carbachol and nicotine, although in these instances the inhibition was less easily reversed by washing with frog Ringer. The inhibitory effect of ACh was blocked by d-tubocurarine but not by atropine. Serotonin (5-HT) caused an increase in the frequency and amplitude of contractions and the effect was blocked by methysergide. No uniform response was observed with 3-hydroxytryptamine (3-HT), but both reserpine and fluoxetine inhibited worm movement. Results suggest that the somatic musculature of the worm is controlled, at least in part, by an inhibitory cholinergic and an excitatory serotoninergic system. PMID- 2594416 TI - The role of parasite fecundity and longevity in the success of Trichostrongylus tenuis in low density red grouse populations. AB - The prevalence of the caecal threadworm Trichostrongylus tenuis in red grouse in the north of Scotland was high despite low grouse densities. Prevalence, intensity and aggregation of threadworms was higher in old than in young grouse. Infections were long-lasting: populations of adult worms could survive for over 2 years in grouse, with little mortality. Parasite egg output decreased with the age of a worm population, largely as a result of a decrease in the fecundity of ageing female worms. Seasonal variations in worm fecundity were also evident. However, there was no evidence of an intensity-dependent decrease of worm fecundity with increasing worm numbers in either captive or wild grouse. The long life and high reproductive capacity of T. tenuis probably contribute to its effective transmission and high prevalence. PMID- 2594417 TI - Factors affecting the establishment of the caecal threadworm Trichostrongylus tenuis in red grouse (Lagopus lagopus scoticus). AB - The resistance of captive reared red grouse to Trichostrongylus tenuis was measured as the proportion of ingested infective 3rd-stage larvae which failed to develop to adult worms. Individual grouse showed wide, repeatable variations in resistance. Seasonal variations may also have occurred. Red grouse acquired little or no effective immunity to reinfection after challenge with a single dose of infective larvae. In trickle-dosed grouse, however, adult worms weakly inhibited the establishment of incoming larvae in an intensity-dependent fashion. Despite this, the proportion of larvae established in trickle infections was similar to that in single-dose challenges. PMID- 2594418 TI - Developmental changes in proteins and glycoproteins revealed by direct radio iodination of viable Taenia saginata larvae. AB - Direct surface 125I radio-isotope labelling techniques and SDS-PAGE analysis were used to compare the proteins and lentil-lectin adherent glycoproteins of the bovine stage of viable Taenia saginata larvae at three points in their development, the invasive oncospheres, immature (4-week-old) and mature (12 to 16 week-old) cysticerci. Some proteins and glycoproteins were present on all three of the ages of the parasite examined but there were also distinct age-specific proteins and glycoproteins detected on oncospheres and 4-week-old cysticerci and a marked difference between the protein/glycoprotein profiles of the parasite was apparent at these earlier stages of development and the mature cysticeri. The latter were characterized by the presence of high, 160-200 kDa molecular weight, lysine rich, glycoproteins, whereas small 16 and 18 kDa glycoproteins and a reduction-sensitive 23 kDa glycoprotein were first detected on 4-week-old immature cysticerci. Antigenic characterization of the isotope-labelled proteins and glycoproteins by immunoprecipitation against a panel of clinically defined bovine sera combined with SDS-PAGE analysis indicated that relatively few proteins were precipitated by sera from T. saginata-infected cattle as compared to the glycoproteins. However, both protein and glycoprotein antigens of possible protective and/or diagnostic significance were identified from oncospheres and cysticerci. Of particular note were low molecular weight oncospheral proteins and low and high molecular weight cysticercal glycoproteins. The immunogenicity of these protein and glycoprotein antigens of T. saginata larvae and their age related changes are of relevance to the design of diagnostic assays, vaccines and possibly to the survival of this parasite in its bovine host. PMID- 2594419 TI - The epidemiology of Ascaris lumbricoides and other soil-transmitted helminths in primary school children from Ile-Ife, Nigeria. AB - An epidemiological survey of intestinal helminthiases was conducted on 766 primary school children aged 5-16 years from Ile-Ife, Nigeria. On the basis of stool examinations, the prevalence of Ascaris lumbricoides, Trichuris trichiura, hookworm and Strongyloides stercoralis was 88.5, 84.5, 33.1 and 3% respectively. Intensity of infection was measured indirectly by egg counts for each species of helminth and also by counting worms passed after chemotherapy in the case of A. lumbricoides. The influence of host age and sex on infection levels was assessed. Relationships between the intensities of A. lumbricoides, T. trichiura and hookworm in individual children were identified. After anthelmintic treatment with levamisole, the frequency distribution of A. lumbricoides per host and the relationship between parasite fecundity and worm burden were investigated. Reinfection patterns of A. lumbricoides were assessed at two 6-monthly intervals and even within the narrow age range described, differences were found. In addition, evidence was obtained for predisposition of individuals to heavy or light infection with A. lumbricoides. PMID- 2594421 TI - The weight/length profiles of Ascaris lumbricoides within a human community before mass treatment and following reinfection. AB - Weight and length profiles are presented of 3505 Ascaris worms recovered after mass anthelmintic treatment of a human community in January 1984 and, after an 11 month period of reinfection, in November 1984. Male and female worms recovered after reinfection were significantly heavier and longer than those expelled after initial treatment (P less than 0.0001). Multiple regression models were employed to examine variability in parasite size. A positive influence of host body weight on the weight of parasites recovered in January, but not in November, was observed. No negative relationship was recorded at either date between worm size and the total number of worms harboured, even after controlling for host weight. Striking host age-related variability was observed in the distribution profile of weights and lengths of individual worms recovered in January. Children harboured predominantly smaller worms before initial treatment, while adults expelled mainly heavy worms. In contrast, worms expelled by both children and adults after reinfection were heavier and more homogeneous in size, particularly within the relatively heavily infected group. These patterns argue against a primary role for density-dependent or acquired resistance mechanisms in determining the size of Ascaris in humans. However, the results are consistent with a hypothesis initially suggested by Jung (1954) that established worms may inhibit the development of newly acquired Ascaris larvae, perhaps regulating their own abundance. PMID- 2594420 TI - Soil-transmitted helminth infections in school children from Cocle Province, Republic of Panama. AB - A survey was carried out to determine values for the prevalence and intensity of infection of intestinal helminths in children living in Cocle Province, Republic of Panama. The data set consisted of the results of microscopic examinations (modified Kato Katz technique) of stool samples collected in November 1987 from 661 children attending primary schools in 4 communities in the province. The overall prevalences of Ascaris lumbricoides, hookworm and Trichuris trichiura infections were found to be 18.2, 12.0 and 27.5% respectively. There were significant differences between the infection prevalence values for children attending the different schools, but not with respect to age or sex. Positive associations were detected between particular pairs of infections and these were most evident when Trichuris trichiura was involved. The data revealed evidence of a positive association between siblings at one school only for each helminth infection. There was extreme variation in the values for intensity of infection (20-126180 epg for A. lumbricoides). Highly significant, and unexplained, differences were observed in the intensity of A. lumbricoides infection by primary school; this finding did not apply to hookworm or T. trichiura. The analysis also revealed that children heavily infected with A. lumbricoides were also likely to be heavily infected with T. trichiura. Comparisons with the results of surveys carried out in Cocle Province in 1926 and 1974 indicate that these infections are declining in this region of Panama. PMID- 2594422 TI - [The activation of specific type-III glucocorticoid receptors by pyrazolone series preparations]. AB - Experiments were conducted on intact and adrenalectomized male Wistar rats (weighing 180-200 g) with labelled corticosterone of high specific activity to study the effect of analgin and aminopyrine on the level of type-III glucocorticoid receptors in the liver. Analgin and aminopyrine in doses of 10(-2) and 10(-3) increase the specific binding of labelled corticosterone by type-III glucocorticoid receptors of the hepatic cytosol and by blood plasma transcortin in modelled experiments. The effect of the agents depends on the dose. Intravenous administration of 140 mg/100 g of analgin to intact rats and intraperitoneal injection of an equal dose of analgin to adrenalectomized rats also increases the specific binding of labelled corticosterone by type-III glucocorticoid receptors of the hepatic cytosol. The importance of the revealed effect of agents of the pyrazolone series in stress regulation is discussed. PMID- 2594424 TI - [Erythrocyte ion transport and membrane potential in patients with chronic kidney failure]. AB - The membrane potential (delta E), the K+ concentration and the Ca2+-dependent potassium permeability of erythrocytes were studied in patients suffering from chronic renal insufficiency (CRI) in the terminal stage and undergoing hemodialysis. Increased absolute delta E value and reduced K+ concentration in the erythrocytes were revealed during the pathological condition. When erythrocytes were de-energized by NaF, addition of Ca2+ led to K+ elimination and proton rebound due to calcium-hydrogen exchange through the membrane. In some cases repeated injections of Ca2+ caused a series of rebounds, potassium penetration diminished in such instances. The proton rebound was absent in almost half of the patients with chronic renal insufficiency and the potassium flow was inhibited. The mechanisms of delta E increase are discussed and it is suggested that the inhibition of Ca2+-induced potassium penetration is due to structural changes of the erythrocyte membranes in CRI. PMID- 2594425 TI - [The social significance of modern medical research]. PMID- 2594423 TI - [The status of the erythrocyte membranes and their functional properties in the postresuscitation period]. AB - It was found that the deformation properties and peroxidation resistance of erythrocytes deteriorate in the postresuscitation period. On the basis of increase of the level of lipoperoxidation products and reduction of the level of alpha-tocopherol and nonprotein sulfhydryl groups, the authors conclude that lipid peroxidation in the erythrocyte membranes is activated after resuscitation. Disorders of molecular interactions are confirmed by the kinetics of nystatin fluorescent probe insertion and revealed increased cholesterol level in the erythrocyte membranes. It is suggested that the increase of the cholesterol level occurring as a protective response to the activation of lipid peroxidation transforms into a pathological reaction causing disorders of the deformation properties and peroxide resistance, which accelerates considerably the natural death of the erythrocytes after resuscitation. PMID- 2594426 TI - [The role of the hematopoietic microenvironment in the mechanism of the antiradiation action of prodigiozan]. AB - Preliminary administration of a radioprotective dose (3 mg/kg) of the bacterial polysaccharide prodigiozan 24 hours before irradiation of (CBA X X C57B1) F1 hybrid mice by a dose of 8 Gr increased the efficacy of exogenous clone formation of intact and irradiated bone marrow significantly. The efficacy of exogenous clone formation increased by 44-82% in transplantation of intact bone marrow and by 180-220% in transplantation of irradiated marrow (as compared to the values in animals who did not receive prodigiozan). This phenomenon was evidently associated with intensified reproduction of the transplanted CFU in mice given prodigiozan, evidence of which is the quantitative dependence of the effect on the dose of the transplanted cells. A conclusion is drawn that one of the aspects of the hematopoiesis-stimulating effect of prodigiosin in an irradiated organism is linked with its effect on the elements of the hematopoietic stroma. It is suggested that agents of other classes may be characterized by a similar mechanism of action; the same effect may be produced by some other factors which reduce radioresistance. PMID- 2594427 TI - [The blood and lymph electrolyte composition in the postresuscitation period]. AB - The electrolyte composition (Na+, K+, Ca2+, Mg2+) of blood serum and lymph was studied in experiments on 17 mongrel dogs in the postresuscitation period after clinical death. The concentration of these electrolytes reduced in the postresuscitation period. Comparison of data obtained in study of blood and lymph showed the revealed changes to be of one trend. The above-said is evidence of the expediency of including in the complex of postresuscitation therapeutic and preventive measures means for normalizing the electrolyte composition of not only the blood but also the lymph. PMID- 2594428 TI - [Theoretical basis and clinical assessment of fluid evacuation from the lungs during bronchoalveolar lavage in children]. AB - The authors discuss the theoretical aspects of the process of lavage fluid absorption from bronchial and alveolar spaces during broncho-alveolar lavage. It is shown that pressure in the vessels of pulmonary circulation, the blood colloid osmotic pressure, and permeability of the alveolar-capillary barrier play an important role in the dynamics of changes of the absorption process. Methods for correcting the intensity of absorption (use of solutions of different osmotic force for lavage) are suggested. Data gained in observation over the use of therapeutic lavage in children confirm the theoretical conclusions and demonstrate the favourable results of lavage in children with atelectases. PMID- 2594429 TI - [The reactivity of pulmonary and hepatic macrophages in normal and prestimulated animals]. AB - The rate of blood clearing of colloidal carbon increased two-fold as compared to the controls 5 days after prodigiosin injection. This was attended by intensified recruitment of macrophages into the alveoli and increase in the number of phagocytizing macrophages in the interstitium of the lungs by 1.5 times above normal. After administration of zymosan granules, the rate of colloid carbon clearance increased 1.5-fold in 5 days and 2.5-fold on the 9th day; the recruitment of macrophages into the alveoli and the number of phagocytizing macrophages in the interstitium of the lungs increased two-fold. At the same time, granuloma-type mononuclear infiltrates formed in the lungs and liver. Prodigiosin injection increases the rate of blood clearance 1.2-fold in animals stimulated by zymosan granules, while the volume of mononuclear infiltration, which acquires a diffuse character, increases 2.5-fold as compared to the value in zymosan stimulated animals. The effects of phagocyte reconciliation may be directly related to exacerbations of chronic inflammatory diseases of different localization. PMID- 2594430 TI - [Microcirculatory disorders in acute ischemia of the small intestine and in the postischemic period]. AB - Microcirculation in the small intestine of rats during ischemia (from 5 to 240 minutes) and in the period of reperfusion (from 60 minutes to 10 days) was studied by biomicroscopy. Ischemia was modelled by ligating the base of the intestinal loop. Sharp microhemodynamic disorders occurred during ischemia, compensatory mechanisms intensifying the blood flow were switched on, the microvascular channel, including vessels which previously did not function, were dilated. Mechanisms concerned with redistribution of fluid in the intra- and perivascular space were evidently the underlying factors of capillary dilatation. In the late-term periods of reperfusion ischemia leads to increase of the number of microvessels in the ischemic part of the organ. PMID- 2594431 TI - [Glycolysis activation, a decrease in the glycogen reserve and the absence of glucocorticoid control over the enzymes of carbohydrate metabolism in the liver of rats under prolonged hypokinetic stress]. AB - The content of 11-oxycorticosteroids in blood plasma, the content of glycogen in the liver and the correlation of processes of glycolysis and gluconeogenesis in it (according to the activity of the key enzymes) were studied in rats in the course of chronic stress (on day 5, 15, 30, 45, and 60) induced by keeping the animals under conditions of severe hypokinesia. The 11-oxycorticosteroic content increased on the 5th, 45th, and 60th day of stress. On the 5th day processes of gluconeogenesis in the liver prevailed over processes of glycolysis, on the 60th day glycolysis prevailed over gluconeogenesis. On the 45th-60th days the content of glycogen in the liver reduces and the activity of the key enzymes becomes exempt from hormonal control. PMID- 2594432 TI - [Thrombogenicity of the arterioles and venules in experimental tumor growth]. AB - The authors studied laser radiation induced thrombogenesis in microvessels- arterioles and venules--of the mesentery of tumor-carrier rats. Statistically significant increase of thrombogenic potential was revealed in the venules on the 7th day after reinoculation of Pliss' lymphosarcoma, and only a tendency to its increase in the arteries. At the same time an increase was noted of the aggregation activity of blood platelets and inhibition of their deaggregation. The results of the study open new aspects of the phenomenon of generalized changes in the system of regional blood circulation characteristic of tumor growth and indicate a new means of its study. PMID- 2594433 TI - [Antiatherogenic properties of the soy protein isolate 500 E]. AB - Two and 4 hours after a single intake of 50 g of protein isolate soy 500 E in the food, the activity of lysosomal hydrolases in blood platelets, the cholesterol (CS) content in lipoprotein-containing immune complexes, and the accumulation of CS in the subendothelial cells of human aorta intima reduced in introduction into a culture of serum obtained after intake of protein isolate soy. Direct introduction of a isolate 500 E water-alcohol extract into a culture of atherosclerotic plaques of human aorta intima caused decrease of the CS content in the cells and their proliferation. Protein isolate soy, therefore, produces an antiatherogenic effect in a cell culture and causes the antiatherosclerotic properties of serum. PMID- 2594434 TI - [A method for the intravital recording of the wall and valve contractions of lymphatic microvessels]. PMID- 2594435 TI - [Determination of the products of lipid peroxidation using thiobarbituric acid under anaerobic conditions]. PMID- 2594436 TI - [The teaching of the section on "Inflammation" in a course on pathologic physiology (grounds for reflections and corrections)]. PMID- 2594437 TI - [A mental experiment]. PMID- 2594438 TI - A pediatrician's view. PMID- 2594440 TI - Holding chambers for aerosol drugs. PMID- 2594439 TI - If you want to know more. PMID- 2594441 TI - [Usefulness of transfusion of a leukocytic mass in the treatment of staphylococcal septicemia in a newborn infant with a disorder of phagocytosis]. PMID- 2594442 TI - [2 cases of nodular pneumonia]. PMID- 2594443 TI - [Clinical symptoms of cardiac tamponade caused by mediastinal emphysema in a 3 year-old child with obstructive bronchitis and pneumonia]. PMID- 2594444 TI - [Endoscopic polypectomy in children]. PMID- 2594445 TI - [Procedures in hospital admissions: tradition and proposals]. PMID- 2594446 TI - [Methemoglobin level and morphology of the blood in children from the State Children's Home in Gda'nsk-Oliwa]. AB - Blood methemoglobin levels and blood cell counts were carried out in 64 children of the State Children's Home is Gdansk-Oliwa. An excessive consumption of nitrites and nitrites leading to the increase in methemoglobinemia and anaemia observe in the previous studies stimulated the present investigations. Methemoglobinemia was detected in 14.1% of children together with marked anaemia especially in the youngest children. The authors suggest that partial elimination of nitrites and nitrates from the diet and periodical analysis of the drinking water and food seem necessary. PMID- 2594447 TI - [Evaluation of the results of the treatment of infections in newborn infants with developmental anomalies of the facial bones]. AB - A clinical course and the results of treatment of infections in 53 neonates with visceral cranium defects are discussed. The analysis included the type of defect, immunity and the causes of therapeutical failures. Developmental defects of other organs coexisted with visceral Cranium defects in 45% of the neonates. High incidence of aspiration pneumonia (in 57%) with unfavourable prognosis (40%) was observed despite an intensive respiratory therapy including assisted ventilation. Therapeutical failures were caused by the coexistence of other developmental anomalies (found in 80% od deceased neonates) and low body weight at birth (35% of deaths). No immunological disorders were found except sporadic deficit of immunoglobulins and T-cells. Prophylaxis is of utmost importance. It includes: early orthodontic correction and introduction of the appropriate feeding technique at the neonatal wards. PMID- 2594448 TI - Review of 40 children with imported malaria. AB - Forty cases of imported malaria (1978 to 1988) are reviewed and management principles are discussed. All 15 cases of Plasmodium falciparum malaria were acquired in Africa, 5 of which were probably chloroquine-resistant. Most cases of Plasmodium vivax (80%) were acquired on the Indian subcontinent, including 2 cases of congenital malaria. Six children developed P. falciparum malaria despite chemoprophylaxis. All children had a history of fever, usually with other influenza-like symptoms. Two-thirds had splenomegaly, and one-third were afebrile on admission. Thrombocytopenia (70%) and anemia (70%) were often present. Forty five percent received previous wrong diagnoses and treatments. Quinine or quinidine with either Fansidar or clindamycin were used to treat P. falciparum malaria. Clindamycin may be more effective if given for 7 instead of 3 days. There were no deaths or residual complications. As the prevalence and severity of drug-resistant P. falciparum spreads, prophylaxis and treatment choices become more difficult. Diagnosis requires a travel history and a high index of suspicion. PMID- 2594449 TI - Clinical and epidemiologic features of mumps meningoencephalitis and possible vaccine-related disease. AB - All cases of mumps meningoencephalitis diagnosed at our institution during the past 15 years were reviewed. There were 24 cases, 16 between 1973 and 1977, 3 between 1978 and 1985 and 5 in 1986 to 1988. Four of the recent cases occurred 19 to 26 days after receipt of a new mumps vaccine (Urabe Am 9 strain) released in Canada in 1986. The remaining 20 cases were clustered in winter and spring. The average age was 6.2 years and the ratio of males to females was 5:1. Clinical presentations were fever (90%), vomiting (90%), meningismus (70%), headache (65%), parotitis (50%) and seizures (30%). The mean cerebrospinal fluid white blood cell count was 513/mm3 (lymphocyte predominance); 55% of patients had a cerebrospinal fluid protein level of greater than 0.4 g/liter, and the cerebrospinal fluid:blood glucose ratio was greater than 0.4 in all. Two patients had adverse sequelae. The clinical and laboratory features of these cases were not significantly different from the vaccine-associated cases. PMID- 2594450 TI - Alpha-streptococcal septicemia in leukemic children treated with continuous or large dosage intermittent cytosine arabinoside. AB - During a 2-year period after the introduction of an intensive chemotherapeutic protocol, alpha-hemolytic streptococci accounted for 75% of all episodes of sepsis among children with acute nonlymphocytic leukemia at our institution. Only one case had occurred in the previous 8 years. Fourteen of 15 episodes of streptococcal sepsis occurred after therapy with either continuous or large dosage intermittent cytosine arabinoside. Eleven episodes occurred at two specific treatment points. Septic episodes were complicated by shock (2 of 15), encephalopathy (2 of 15), pneumonia (3 of 15) and death (1 of 15). Oral mucosal lesions may provide a portal of entry for alpha-hemolytic streptococci. These data suggest that children receiving continuous or large dosage intermittent cytosine arabinoside for treatment of acute nonlymphocytic leukemia may be at increased risk for alpha-hemolytic streptococcal sepsis. Empiric antimicrobial therapy in these children when febrile and neutropenic should include antibiotics effective against alpha-hemolytic streptococci. PMID- 2594451 TI - Detection of circulating antibodies to purified protein derivative by enzyme linked immunosorbent assay: its potential for the rapid diagnosis of tuberculosis. AB - An enzyme-linked immunosorbent assay for detecting antibodies to purified protein derivative was evaluated as a rapid method for serodiagnosis of childhood tuberculosis. Its specificity for IgG antibodies was 0.98 as determined in 55 sera from nontuberculous children who showed no significant effect of previous Bacillus Calmette-Guerin vaccination on the production of specific antibodies. Results were negative in 29 of 33 (87.9%) tuberculin-positive children and in 18 of 20 (90.0%) contacts, none of whom had evidence of tuberculosis. The sensitivity of this test was 0.51 as determined in 49 sera from bacteriologically confirmed cases; 17 of 27 smear positive cases and 8 of 22 children with positive cultures were detected. Results were positive in 32 of 114 (28.1%) patients with a diagnosis of tuberculosis not confirmed by microbiology. Consequently whereas a negative result does not rule out tuberculosis, a positive result is a strong indication of the disease. The IgM antibody determination yielded much less discriminative results. PMID- 2594452 TI - Causes of death and the histopathologic findings in fatal shigellosis. AB - Thirty-seven children (median age, 2 years) with shigellosis in Bangladesh were subjected to postmortem examination to determine causes of death and the spectrum of intestinal histopathology. Infecting species were: Shigella dysenteriae 1, 7 cases; S. dysenteriae 2, 2 cases; Shigella flexneri, 23 cases; Shigella boydii, 4 cases; and mixed infection with Shigella boydii and Shigella sonnei, 1 case. Complicating conditions detected before death included malnutrition in 25 cases, pneumonia in 11 cases and septicemia in 8 cases. In all 37 cases the colon showed gross colitis, consisting of mucosal erythema and edema; superficial ulcerations were visible in 15 cases. Microscopically in the colon the lamina propria showed inflammatory cellular infiltration in 27 cases and crypt abscesses were present in 22 cases. In 9 cases each there were colonic glands in the submucosa and branching of colonic crypts, indicating increased regenerative activity of crypt cells. Severe lesions were mucosal denudation and deep ulceration in 15 cases with a pseudomembrane in 7 and pseudopolyposis in 2 of these patients. The most common underlying cause of death was colitis, whereas the most common immediate and associated causes were, respectively, septicemia and pneumonia. These results indicated that fatal childhood shigellosis results from severe colitis, often complicated by septicemia and concomitant malnutrition and pneumonia. PMID- 2594453 TI - Anatomic and audiologic sequelae after tympanostomy tube insertion or prolonged antibiotic therapy for otitis media. AB - In this study the anatomic and hearing sequelae are characterized for 43 children (86 ears) with recurrent acute otitis media and/or persistent otitis media with effusion who had received three or more tympanostomy tube placements and 46 children (92 ears) managed medically with repeated courses of therapeutic and/or or prophylactic antibiotics. In the surgical group 311 tympanostomy tube surgeries had been performed and in the medical group 1334 episodes of acute otitis media and/or 186 episodes of otitis media with effusion occurred. Tympanosclerosis was found in 6.5% of the medical group ears and 52.3% of the surgical group ears. Tympanic atrophy occurred in 4.3% of the medical group ears and 40.7% of the surgical group ears. The duration of the presence of the tympanostomy tube significantly influenced the tympanic membrane. The presence of middle ear fluid at the time of tube insertion, particularly high viscosity ("glue") fluid, correlated with persisting sclerosis (P less than 0.00001) and reduced tympanic membrane mobility (P less than 0.00001) but not tympanic membrane atrophy (P = 0.94) later. Abnormal hearing, defined as a hearing threshold greater than 20 dB occurred in 9.3 to 18.7% of the surgical ears and in 3.7 to 9.0% of the medical ears depending on the hearing frequency tested. Medical management consisting of recurrent use of therapeutic and/or prophylactic antibiotics was associated with infrequent anatomic and audiologic sequelae. Repeated placement of tympanostomy tubes may be associated with the frequent occurrence of both anatomic and audiologic sequelae. PMID- 2594454 TI - Infective endocarditis in black South African children: report of 10 cases with some unusual features. AB - Ten black South African children with infective endocarditis seen over a 2-year period are reported. In five cases, including two neonates, the infection was nosocomial and in five cases it occurred in children with previously normal hearts. Of the bacteria isolated from nine cases, five were Staphylococcus aureus (all from nosocomial cases), one was Haemophilus influenzae and three were corynebacteria. The unusual aspects of this series are discussed, with an emphasis on preventing nosocomial cases and on making the diagnosis in children without underlying heart disease. PMID- 2594455 TI - Increased risk of primary invasive Haemophilus influenzae type B disease in twins. PMID- 2594456 TI - Pharyngitis-associated M-12 group A Streptococcus satellite strain: association with Neisseria subflava. PMID- 2594457 TI - Transient cataracts in a young child with meningococcal meningitis. PMID- 2594458 TI - Cryptococcus laurentii infection complicating peritoneal dialysis. PMID- 2594459 TI - Haemophilus vaccine efficacy in Dallas County. PMID- 2594460 TI - Amoxicillin as the drug of choice for acute otitis media: isn't it time for its reassessment in some areas of the country? PMID- 2594461 TI - Community-acquired infection with methicillin-resistant Staphylococcus aureus in Papua New Guinea. PMID- 2594462 TI - Hepatic abscess and Peptococcus bacteremia. PMID- 2594463 TI - Empiric therapy with acyclovir for suspected neonatal herpes simplex infection. PMID- 2594464 TI - Diagnosis of streptococcal pharyngitis. Proceedings of a symposium. Boston, MA, June 30, 1989. PMID- 2594465 TI - Evaluating the impact of a home screening test for streptococcal pharyngitis. AB - Home screening tests must be evaluated as an aid to self-referral to a physician and should not be judged as if they were diagnostic procedures, i.e. the sole determinants of a therapeutic decision. The performance characteristics of a test are properly compared to those of the patient or parent, operating in the absence of the test. For streptococcal pharyngitis there would be a net increase in the number of cases correctly treated whenever the sensitivity of the home test (multiplied by the probability that the patient will act upon the test results) exceeds the a priori probability that the patient will be seen by a physician in the absence of the test. Use of home screening tests is likely to increase the number of patient-physician contacts among persons with sore throats and will do so proportionately more frequently among those with streptococcal pharyngitis. PMID- 2594466 TI - Rapid assay for the in vitro chemosensitivity testing of human breast tumours. Control of assay conditions and quality assurance. AB - This study has been initiated by the definite need of a rapid, in vitro and patient-specific test to examine oncolytic drug effects on tumour cells. Therefore, we applied a test in which we monitored the incorporation of labelled nucleosides in isolated tumour cells, as a measure of nucleus activity (i.e. the Volm assay). A novel technique of erythrocytes co-precipitation has been developed and this enabled us to use a small number of tumour cells per test (200,000 cells/tube). During the assay, a strict pH control and a high starting viability have been introduced. A cytotoxic control and a t-test at two levels deal with the technical errors and the imprecision. For the evaluation of a specific drug a number of 1.8 million cells proved to be sufficient. Time-course studies of the incorporation of labelled nucleosides into isolated tumour cells have shown the optimal incubation time to be 2 h. The entire assay is completed within one day. HeLa cell cultures were employed as quality control material and criteria for interpretation have been developed. Preliminary results, based upon the evaluation of 43 human breast tumours with doxorubicin, indicate the correctness of the proposed procedures. In conclusion we can state that this assay not only provides useful information but above all that the results are made available in such a short time that they can be used directly in the medical management of the individual patient. PMID- 2594467 TI - Flavones and flavonol glycosides from Eupatorium cannabinum L. AB - The 6-methoxyflavones hispidulin and eupafolin have been identified for the first time from the aerial parts of Eupatorium cannabinum L. The presence of the previously known flavonol glycosides astragalin, kaempferol-3-rutinoside, hyperoside, isoquercitrin and rutin could be confirmed. Hispidulin, eupafolin and rutin were screened for cytotoxicity in vitro. PMID- 2594468 TI - Faecal level of urobilinogen: an indication for the risk of superinfection and of failure of oral anticonception? AB - The influence of clindamycin, dicloxacillin, minocycline and norfloxacin on the faecal concentration of urobilinogen was investigated. The studied drugs were administered orally in standard dosage for six days to groups of six volunteers. A decrease in faecal concentration of urobilinogen following administration of clindamycin (P less than 0.01) and dicloxacillin (P less than 0.05) was found. The possible predictive value of a decrease of the faecal level of urobilinogen as an indicator for the impairment of microbial colonization resistance and for the risk of failure of oral anticonceptive treatment is discussed. It is suggested that clindamycin and dicloxacillin should not be combined with oral anticonceptive treatment unless more specific investigations have excluded interaction of these drugs with the oestrogen metabolism in the bowel. PMID- 2594469 TI - The use of an alum irrigation in the treatment of massive bladder haemorrhage. AB - Severe, massive bladder haemorrhage is a difficult and often frustrating clinical problem. The aetiologies are numerous and include irradiation, malignancy, severe infection and drug-induced changes. Among the numerous modalities of treatment that have been reported formalin, phenol and silver nitrate instillations have often been associated with significant side effects, morbidity and mortality and have had varying degrees of success. During the last two years we have used continuous closed irrigation of a sterile 0.5% alum solution in 16 patients. Alum is an astringent and acts by protein precipitation over the bleeding surface. Because of a low cell permeability its action is limited to the cell surface and interstitial spaces. The permeability of the cell membrane is reduced but remains viable. The preparation and the pharmaceutical aspects of the 0.5% alum irrigation will be discussed. The conclusion is that the technique of managing massive bladder haemorrhage is simple, efficient, nontoxic and less expensive than previously reported therapies. Therefore, irrigation with alum before instituting invasive means to control bleeding is recommended. PMID- 2594470 TI - Abstracts of papers. Rational use of drugs. 18th European Symposium on Clinical Pharmacy. Nijmegen (The Netherlands), 25-28 October 1989. PMID- 2594471 TI - Compared properties of the contractile system of skinned slow and fast rat muscle fibres. AB - Chemically skinned fibres from soleus and plantaris rat muscles were used to compare the contractile properties of slow and fast muscles. The maximal isometric tension appeared larger in plantaris than in soleus fibres. The apparent Ca2+ threshold for activation was lower in slow than in fast fibres while Ca2+ concentrations required to obtain either the maximal tension or half maximal tension (pCa50) were lower in fast than in slow fibres. This apparent difference in Ca2+ sensitivity will be discussed. As could be expected from other studies, a faster force development in plantaris than in soleus fibres occurred. However, one interesting new result showed that in soleus, the kinetics of the tension development estimated by the tmax parameters were slightly dependent on the Ca2+ concentration whereas the t50 parameter changed significantly with the Ca2+ concentration. In plantaris, both tmax and t50 parameters were found to depend strongly on the Ca2+ concentration. Finally, the plantaris muscle showed a greater caffeine sensitivity than the soleus muscle. All the results suggested that the Ca-regulatory mechanism in the slow fibres was essentially different from that in the fast fibres. PMID- 2594472 TI - Time-dependent effects of aldosterone on sodium transport and cell membrane resistances in rabbit distal colon. AB - Aldosterone stimulates Na+-absorption in rabbit distal colon. Due to circadian variations in plasma aldosterone level, Na+-transport varies in this epithelium. In vitro measurements (Ussing-chambers) yielded a trans-epithelial voltage (Vt) of 13 +/- 1.6 mV for low-transporting epithelia (LT) and 25.7 +/- 2 mV for high transporting epithelia (HT). However, the comparison of transepithelial conductance (Gt) in LT epithelia (2.73 +/- 0.21 mS/cm2) and HT epithelia (2.96 +/ 0.41 mS/cm2) revealed no difference. Colons from both groups were stimulated by exogenous aldosterone (4 h prior to experiment). The transepithelial values changed as follows: LT epithelia showed a significantly increased Vt (26.1 +/- 4 mV) and Gt (3.74 +/- 0.23 mS/cm2), whereas in HT epithelia both parameters remained unchanged. Transepithelial amiloride-sensitive conductance was higher in HT than in LT. However, only in LT epithelia aldosterone increased this conductance. To get a more detailed view of the action of aldosterone, we used intracellular microelectrodes to calculate the resistances of apical (Ra), basolateral (Rbl) and paracellular (Rp) pathway. The calculation of the resistances was based on a lumped equivalent circuit model and changes in Ra were induced by 50 microM/l mucosal amiloride. Comparison of the control tissues revealed a lower Rbl only in HT tissues. In both groups stimulation by exogenous aldosterone led to a marked decrease of Ra. Furthermore Rbl was reduced to the same value as in HT control tissues. A leak resistance (Rl) was found, which was modulated by aldosterone in LT- and in HT epithelia. Differences in amiloride sensitive transepithelial conductance between both epithelia groups could be explained by a regulation of Rl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2594473 TI - Zinc inhibition of glucose uptake in brush border membrane vesicles from pig small intestine. AB - The effect of zinc on sodium coupled glucose uptake was studied in pig intestinal brush border membrane vesicles. In this system zinc inhibited glucose uptake and appeared to have a Ki of 0.25 mM. When tested by spectrophotometry, electron microscopy and protein determination following centrifugation, no evidence of significant vesicle aggregation was found with 0.5 mM zinc treatment. Zinc inhibition of glucose uptake persisted when the vesicle membrane potential was clamped with identical KCl concentrations inside and outside the vesicles in the presence of valinomycin. Variation of the glucose and sodium concentrations gave results indicating that zinc reduces glucose affinity for the carrier but not sodium binding to the transporter. The glucose inhibitory effect was not due to a rapid dissipation of the sodium gradient as zinc failed to affect sodium uptake in the absence of glucose. Zinc also failed to inhibit glucose efflux from vesicles under isotopic exchange conditions, when glucose and sodium concentrations were identical inside and outside vesicles. The t1/2 of glucose inhibition by zinc was relatively long, i.e. 6 min. We conclude that zinc acts as an inhibitor of glucose transport by interacting with the sodium-glucose co transporter. The long zinc incubation time required to achieve maximal inhibition of glucose transport suggests that this interaction takes place within vesicles. PMID- 2594474 TI - Electrical properties of cultured renal tubular cells (OK) grown in confluent monolayers. AB - OK cells grown to confluent monolayers were investigated by microelectrode techniques and microinjection. Cell membrane potential difference (PDm) in bicarbonate-free solution is -61.8 +/- 0.6 mV (n = 208), cell membrane resistance (Rm) amounts to 1.4 +/- 0.2 k omega. cm2 (n = 8). The apparent transference number for potassium (t'k+) is 71 +/- 3% (n = 28) and can be reduced by 3 mmol/l BaCl2 to 7.5 +/- 4.0%; (n = 8). In the presence of extracellular CO2 and HCO3- (pH 7.4) the cells acidify by 0.34 +/- 0.05 pH units (n = 12). This leads to a depolarization of PDm by 8.4 +/- 1.8 mV (n = 8), an increase in Rm by 49 +/- 10% (n = 10), and a reduction of K+-conductance to 63 +/- 5% (n = 13). Intracellular acidification by the NH4Cl-prepulse technique also inhibits K+-conductance and depolarizes the membrane. Recovery from an intracellular acid load is reflected by cell membrane repolarization. This recovery can be inhibited by amiloride (10( 3) mol/l). Na+- and Cl- -conductances could not be detected. The transepithelial resistance (Rte) of OK cell monolayers 1 day after plating is 41 +/- 6 omega.cm2 and decreases with time after plating. Intercellular communication (electrical or dye coupling) was not observed. CONCLUSIONS: 1. The membrane potential of OK cells is largely determined by a pH-sensitive, barium-blockable K+-conductance. 2. Amiloride-blockable Na+/H+-exchange is reflected by membrane potential changes via this K+-conductance. 3. Monolayers of OK cells are electrically leaky. PMID- 2594475 TI - Na/Ca exchangers in collecting cells of rat kidney. A single tubule fura-2 study. AB - Single pieces of fura-2-loaded cortical collecting tubule (CCT) isolated either from normal or adrenalectomized (ADX) rats were superfused in vitro, and the cytosolic calcium concentration [( Ca2+]i) was calculated from fluorescence recordings. The effects of altering the sodium gradient across cell membranes were investigated. Switching external sodium from 164 mM to 27 mM (low [Na+]o) had little effect on [Ca2+]i in normal tubules (106 +/- 9 versus 101 +/- 9 nM, n = 15) whereas it resulted in a large peak of [Ca2+]i in CCT from ADX-rats (270 +/ 32 versus 135 +/- 11 nM, n = 21). Since CCT from ADX rats are known to have a reduced Na-pump activity, the effect of ouabain treatment on CCT from normal rats was also tested. When CCT from normal rats were exposed to 1 mM of ouabain in the presence of 164 mM of [Na+]o, [Ca2+]i increased only moderately (123 +/- 15 versus 111 +/- 11 nM, n = 13); when the low [Na+]o solution was applied to these ouabain-treated tubules, a large and transient increase in [Ca2+]i was obtained (287 +/- 38 versus 123 +/- 15 nM, n = 13). This response was absent with [Ca2+]o = 0. The data suggest the presence of 3 Na+/1 Ca2+ exchangers in cell membranes of rat CCT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2594476 TI - Gene transfer by lipofection in rabbit and human secretory epithelial cells. AB - Lipofection, a recently-developed method for gene transfer, was tested in secretory epithelial cells. Lipofection facilitated both transient DNA transfection with plasmids containing the chloramphenicol acetyltransferase gene and stable transfection with a plasmid containing the neomycin resistance gene, which confers resistance to the antibiotic G418 (Geneticin). Gene transfer occurred efficiently in a rabbit kidney medullary thick ascending limb cell line and in primary cultures of rabbit tracheal epithelial cells. The method was also effective in Simian virus 40-transformed human airway cells isolated from a normal individual and from a patient with cystic fibrosis (CF). Cytotoxicity was minimal, particularly when the time of exposure to the lipofectin-DNA was limited to 3-5 h (less than 5% cell loss). Thus, the lipofection method is useful for gene transfer in a variety of secretory epithelial cells and should be ideal for studies of defective secretory epithelial cell function in CF. PMID- 2594477 TI - Discrepancies between myocardial blood flow and fiber shortening in the ischemic border zone as assessed with video mapping of epicardial deformation. AB - Myocardial function around the border of ischemia was investigated in eight open chest dogs using video mapping of epicardial deformation. With this method, 40-60 white markers attached to the left ventricular epicardium were traced in time automatically. Before and 5-10 min after coronary artery occlusion, blood flow and epicardial deformation were determined in 30-40 regions with a spatial resolution of about 5 mm. Epicardial deformation was expressed as subepicardial fiber shortening and surface area decrease during the ejection phase. The latter indicates local contribution to stroke volume. The absolute values of these variables were normalized relative to the central ischemic (= 0%) and remote non ischemic area (= 100%). The 50% contour line of a variable was defined as its border. The average distance between the borders of perfusion and function was not significantly different from zero, due to considerable variation in this distance both within one heart (+/- 5.7 mm) and between mean distances for different hearts (+/- 4.4 mm). The width of the transition zone (distance between the 20% and 80% contour lines) of surface area decrease and subepicardial fiber shortening was significantly larger (20.5 and 15.0 mm, respectively) than those of transmural and subepicardial blood flow (8.5 and 9.5 mm, respectively). The present results demonstrate that in a 20-mm zone around the border of ischemia, major discrepancies are present between perfusion and deformation. PMID- 2594478 TI - Angiotensin II desensitization and Ca2+ and Na+ fluxes in vascular smooth muscle cells. AB - The role of ion fluxes in angiotensin II (AII) desensitization (tachyphylaxis) was investigated by studying Na+ and Ca2+ translocation in cultured vascular smooth muscle cells from the rat aorta. The effects of AII were compared to those of [1-sarcosine]-AII (Sar1-AII), an analogue which also induces tachyphylaxis, and [2-lysine]-AII (Lys2-AII), an analogue that does not show this property. Maximally effective concentrations of the three peptides induced a rapid and transient increase in 45Ca2+ efflux, a rapid and sustained decrease in total cell Ca2+ and an increased Na+ permeability. Repeated treatments, at short intervals, with either of the three peptides abolished the effect on Ca2+ efflux, and this desensitization was slowly reversible. A 30-min rest period was sufficient for full recovery of the response of cells that were desensitized by Lys2-AII, whereas the recovery from AII or Sar1-AII-desensitization was still not complete after 60 min. Our results suggest that the difference in the behaviour of the "tachyphylactic" AII and Sar1-AII and the "non-tachyphylactic" Lys2-AII lays not in the production of different signals upon binding to the receptor, but in a difference in the hormone-receptor interaction itself. PMID- 2594479 TI - A method to quantify and correct for edge leaks in Ussing chambers. AB - A technique is presented which allows edge leaks in Ussing chambers to be detected and quantified. It is based on the fact that in leaky chambers direct current or low frequency alternating current passes preferentially around the edge of the tissue, while high frequency alternating current shunts the cell membranes and distributes homogeneously through the entire chamber. By measuring the current density in the center of the chamber with low and high frequency alternating current and using correction factors which account for the shape of the electrical field as a function of chamber geometry and of estimated tissue resistance, edge leaks can be quantified. This technique allows correct transepithelial resistance values to be obtained from leaky measurements, and enables the question of whether a given discrepancy between cellular and transepithelial resistances reflects leaky tight junctions or a leaky chamber or both to be answered. PMID- 2594480 TI - The effects of pinacidil and tolbutamide in feline pial arteries in situ. AB - The vasomotor effect of the K+ channel opener pinacidil was investigated in feline pial arteries of the parietal cortex. Perivascular microapplication (5 microliters in 40 sex) and an image splitting method for the measurement of vascular diameter were employed. Pinacidil (10(-11) - 10(-7) M) induced concentration-dependent dilatations at 10(-9) M and higher concentrations. A maximal dilatation of about 42% was achieved at 10(-8) M, the dilatation at 10( 7) M was reduced to 22%. The sulphonylurea tolbutamide exerted per se no effect in pial arteries but it blocked concentration-dependently the pinacidil induced dilatation. This is consistent with the presence of ATP-sensitive K+ channels in pial arteries which are closed under resting conditions. PMID- 2594481 TI - [Renal accumulation of technetium-99m-labeled bone imaging agents in patients treated with cisplatin]. AB - As the routine follow-up studies in patients with malignant diseases, bone scintigraphy is often performed to detect bone metastasis, before, during and/or after the treatments. Among these patients who were treated, especially, with CDDP, we often encountered the markedly increased renal radioactivity during the follow-up period by bone scintigraphy. In this study, 68 patients with 76 bone scintigraphy performed within 30 days after the administration of CDDP were evaluated. Forty-five of the 76 bone scintigraphy (60.5%) in the 68 patients exhibited more prominent accumulation of the radionuclide in the kidneys than that normally seen. Among them, twenty-four cases (31.6%) showed markedly increased accumulation of the radionuclide in the kidneys so called the "hot kidneys", when the bone scintigraphy was performed later than 3 weeks after the treatment with CDDP. Moreover, the frequency of the "hot kidneys" were well correlated with the degree of renal damage in terms of serum creatinine levels. These findings suggest that the "hot kidneys" might represent the presence of transient renal damage caused by the administration of CDDP. As the causes of this finding called as the "hot kidneys", various factors and/or many causes are reported recently, however, the highest incidence of this phenomenon is thought to be occurred by CDDP as the factor of drug incidence. PMID- 2594482 TI - [Evaluation of CRT images of digitized film angiographs]. AB - X-ray sheet film images of the test chart, the vascular phantom and angiography were digitized at sampling pitch of 0.2 mm and 0.15 mm using film digitizer TFR 01 (Toshiba) and transferred to a device for image storage and display system with 1635-line display monitor (TDF-500AS, Toshiba). Comparison of image qualities between film- and CRT-images was performed in fundamental and clinical studies. Resolution of the test chart image of conventional radiography was worse on CRT than on the original film, although it was improved when film image was digitized at resolution of 0.15 mm/pixel in comparison with that at resolution of 0.2 mm/pixel. Moire stripes which occurred due to interference were found on CRT images taken using a grid technique. On CRT images of X-ray sheet film using direct magnification technique moire stripes were not produced because of non grid technique, and the resolution approached that of the original film. In the study using vascular phantom, the optimal image on CRT could be obtained by various image processing procedures, and image quality on CRT with resolution of 0.15 mm approached that of original film. In case of direct magnification CRT images were superior to film images. Subtraction image of the vascular phantom at resolution of 0.2 mm/pixel was obtained on CRT and compared with film subtraction image. On conventional subtraction CRT image moire stripes impaired the image quality in comparison with the film subtraction. However, magnification subtraction image of the vascular phantom on CRT was superior to the film subtraction. The results obtained in the test chart studies and phantom studies were also confirmed in clinical studies using various kind of angiograms. In addition, ROC study using clinical angiograms showed no significant statistical differences between the original film and CRT image even with 0.2 mm matrix size. Angiographic image on CRT at resolution of 0.15 mm/pixel or less is available for clinical use in place of conventional film image. PMID- 2594484 TI - [Reparative effects of sodium alginate (Alloid G) on radiation stomatitis]. AB - Discontinuation or alteration of the schedule of radiation therapy is often necessary in patients with tumors of the parotid gland and pharynx because of the development of stomatitis. Alloid G (Sodium alginate; AL-G) is an agent with a promotive effect on healing of inflammation of the gastric and esophageal mucosa. In this study, we orally administered the agent in irradiated mice to examine its healing effect against radiation stomatitis. ICR mice (5-week-old males) were subjected to gamma-irradiation at 17-32 Gy, and followed by oral administration with either AL-G, polyvinyl pyrrolidone (PVP), or water twice daily for 20 days. The effects of the treatments on radiation stomatitis were examined according to the survival of the animals and histological findings in the oral mucosa. After irradiation at 32 Gy, it was found that the epidermal basal layer was present in the AL-G group. In both PVP and water-treated groups, however, it was not found. The dose modification factor (DMF) of 1.12 was calculated from oral radiation death of LD50/20 and radiation dose with or without AL-G. These results suggest that AL-G probably have a pharmacologically reparative effect on radiation injury of the oral mucosa, in addition to the physical epidermal protective effect due to its viscosity such as that of PVP. PMID- 2594483 TI - [Pulmonary nodule detection of chest phantom with CRT images--comparison with conventional radiography (film-screen system) and FCR (Fuji Computed Radiography) hardcopy]. AB - Conventional Radiography, Fuji Computed Radiography (FCR) hardcopy and CRT images were evaluated about the detectability of pulmonary nodule using the chest phantom. Conventional and digitized chest radiographs (FCR) were used, including 45 normal cases and 45 abnormal cases with a variety pulmonary nodule. Observer performance tests were conducted to compare the effects on diagnostic accuracy of Conventional Radiography, FCR hardcopy and CRT images, and diagnostic accuracy was determined with receiver operating characteristic (ROC) analysis. ROC study was performed in which six radiologists were asked to locate nodule on three modalities. Two CRT monitors were used to observed CRT images. The left side CRT monitor was divided into two parts and displayed two images which were done as same image processing as FCR hardcopy. The right side CRT monitor was divided into four parts and displayed four images as a subsidiary diagnosis. The upper two images were displayed to diagnose the nodule of cardiac and diaphragmatic area, and lower two images were displayed to diagnose the nodule of the lung field. The results were summarized as follows: 1) CRT images were superior in sensitivity (78.5%) to the others, and FCR hardcopys were superior in specificity (95.9%). 2) About the accuracy of 5 and 8 mm in diameter nodule detection, there was no significant difference among three modalities. 3) Diagnostic accuracy of 3 mm in diameter nodule detection was significantly greater with digitized radiographs (FCR 44.4%, CRT images 54.4%) than with conventional radiograph (17.7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2594486 TI - [Development of a J-shaped sheath and its usefulness for angiography]. AB - We developed a new sheath for selective trans-brachial and trans-femoral arteriography. This sheath has a J-shaped tip and can be inserted by the conventional Seldinger method using a linear dilator. This sheath was particularly useful for abdominal angiography via the brachial artery and pelvic arteriography via the femoral artery. PMID- 2594485 TI - [Experimental studies concerning comparison of the effect on the intestine between antitumor agents and radiation]. AB - Though radiotherapy combined with chemotherapy is used increasingly more frequently in the recent treatment of malignant tumors, very little is known about what dose of an antitumor agent equals what radiation dose in effect. We tried to determine those radiation doses which are required to produce the same effect as certain specific doses of antitumor agents (isoeffective dose) by studying the early effects of radiation and drugs chiefly on the intestine of dd strain mice. Parameters used were food consumption, body weight change, 3H-TdR radioactivity in the intestine and the labelling index of intestinal crypt cells. The results were as follows: 1) To determine that radiation dose which is equal to a drug dose (1/2 its LD50) in systemic effect, body weight change and food consumption were suggested to be useful parameters. 2) To determine that radiation dose which is equal to a drug dose in the effect on a specific organ, parameters suitable for the target cells must be selected. For evaluating the effect on the intestine, the labelling index of intestinal epithelium was a useful parameter. 3) The results of treatment with combined radiation and slight amounts of drugs suggested that the degree of aggravation of radiation injury due to drugs might vary with the time of drug administration. 4) Graphic representation of the severity of injury as indicated by parameters enabled us to grasp visually the characteristics of drugs. PMID- 2594487 TI - [MR imaging of femoral head avascular necrosis with STIR sequence]. AB - The uncomplicated bone necrosis is usually demarcated by reactive interface (RI). To analyze signal characteristics of RI, MR imaging of the hip was done using short TI IR (STIR) as well as short/long TR pulse sequences at 0.22 tesla. On STIR sequence the RI was observed as a high-signal line or ring with the shape identical to that of short TR image. The double line sign was not seen in early stage. The best explanation of high signal intensity of RI on STIR is that it has prolonged T1 and T2 secondary to high water content. It is concluded that STIR is an unique way to demonstrate RI in early osteonecrosis. PMID- 2594489 TI - [Clinical application of FCR (Fuji Computed Radiography) for portable chest radiographs in the ICU]. AB - The diagnostic value of the portable chest radiography obtained with Fuji computed radiography (FCR) was evaluated in comparison with conventional images in 23 patients who were admitted to ICU in Yokohama City University Hospital. On the whole, FCR produced more excellent images than conventional screen-film radiographs. Especially the evaluation for the demonstration of the catheters, the endotracheal tubes and the tracheal shadows obtained high score. We discuss the clinically utility of FCR for the portable chest radiographs in ICU. PMID- 2594488 TI - [Clinical investigation of the branching formation of the bronchial arteries in the Japanese]. AB - It is imperative to be familiar with anatomical variation in the branching formation of the bronchial artery for radiologists attempting an interventional angiography to the pulmonary diseases such as hemoptysis or pulmonary carcinoma. The anatomy of the bronchial arteries reported by Cauldwell et al. is the most frequently quoted literature in the world as well as in Japan. However, we had noticed that some discrepancies exist between our clinical experience and those in Cauldwell's report regarding anatomical variation of the bronchial arteries. Then, we reviewed the bronchial arteriograms in 640 patients. We included 412 patients in investigation, in which it was possible to identify the branches supplying all pulmonary lobes. In 50 out of 640 patients, catheterization of the branches supplying the lesion was failed. Branching formation of the bronchial arteries is extremely variable and complicated by presence of the accessory bronchial arteries and anastomosing branches from the systemic arteries, which may be enlarged in various pathological conditions. Our results showed that the most common branching type was single artery on each side (50.0%), followed by common trunk (14.1%). The incidence of single on the right and dual on the left, most common in Cauldwell's series, was only 12.9%. Kasai and Chiba also pointed out these differences in their detail report investigating 100 cadavers. These discrepancies between the data may be due to differences of methodology or due to differences between the races. The authors feel that Cauldwell's data should not be referred to the anatomical variation of the bronchial artery in Japanese. PMID- 2594490 TI - [Evaluation of bone mineral density with dual energy quantitative computed tomography (DEQCT)]. AB - Quantitative computed tomography (QCT) has been found useful in the evaluation of vertebral bone mineral density (BMD). It separates cortical from trabecular bone in the vertebral bodies. The accuracy of QCT, however, is limited because of the existence of unknown amounts of marrow fat in the trabecular bone. The purpose of this study is to investigate the precision and accuracy of QCT, with a particular emphasis on the advantage of dual energy technique over single energy technique, as well as to investigate age-related change of BMD in patients with no metabolic disorders. For evaluation of BMD, SOMATOM DR-H CT scanner was used, which provided dual energy scan with rapid kilovolt peak switching system. The lumbar vertebrae (L1-L3) were exposed at the middle portion together with the calibration phantom (Ca10(PO4)6(OH)2 200 mg/ml, 0 mg/ml). KV-separated images (KV HI, KV-LO) and material-separated images (MAT-HI, MAT-LO) were calculated from dual-energy scan data. KV-separated data were considered as SEQCT data. In experiment, dipotassium hydrogen phosphate (K2HPO4) solution was used to simulate bone mineral, water to simulate lean soft tissue and ethanol (C2H5OH) to simulate fat. To investigate the variations originating from marrow fat, a series of phantoms (K2HPO4-C2H5OH-H2O mixtures) with a constant 10 gm% K2HPO4 concentration but with the various mixtures of C2H5OH ranging from 0-40% by volume was scanned with dual energy technique. The value of BMD obtained from KV-separated data was reduced about 12% per 10% fat by volume increase, while the value obtained by DEQCT technique was reduced 5.5% per 10% fat by volume increase. With the dual energy technique the error was greatly reduced. On the other hand, the higher precision of KV-separated images compared to MAT-HI images was obtained, as well as the relatively higher precision for determining high rather than low fraction of mineral. In conclusion, with the single energy technique, precision is high, and with the dual energy technique, accuracy is high. It was also noted that selection of the CT section was the most critical factor in clinical BMD analysis. Age-related change of BMD in vertebral trabecular and cortical bone was studied in 161 patients without bone metabolic disorders. There were two peaks of BMD in females in their 20s and 30s, and a single peak in males in their 20s.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2594492 TI - [The patient as a flight passenger]. PMID- 2594491 TI - Entry-level competencies of graduates of educational programs in practical nursing. PMID- 2594493 TI - [SOS-International--a safety for Scandinavian tourists, but choose destinations suitable to your health status]. PMID- 2594494 TI - [Scandinavian insurance stipulations for travel abroad]. PMID- 2594495 TI - [Medical responsibilities during flights]. PMID- 2594496 TI - [Mumps]. PMID- 2594497 TI - [Why do musculo-skeletal stress injuries increase?]. AB - The innovation of technologies in the industrial countries in recent decades has involved increased physical monotony and inactivity in working life. Parallel to this development the ergonomic quality of work station design has been improved. But the corresponding reduction in physical stress does not seem to diminish the frequency of symptoms from the locomotor system. On the basis of studies carried out in recent years, a U-shaped relationship between physical stress and symptoms is suggested, i.e. frequency of symptoms may increase not only when the physical stress is high but also when it becomes very low. It is concluded that further research on acceptable physical stress should comprise studies aimed not only at upper but also at lower limits, including minimal variation of the physical load. PMID- 2594498 TI - [Raised expectations of the right of self-determination in Estonian health care from 1990]. PMID- 2594499 TI - [Evaluation of scientific quality using citation analysis and other bibliometric methods]. AB - Bibliometric methods for scientific evaluation are examined. The citation frequency for scientific publications, as given in the Science Citation Index, is influenced by various forms of citation bias as well as by the characteristic dynamics and citation practices of the various scientific fields, and therefore cannot be taken as an unequivocal measure of scientific quality. Even for single authors the citation frequency is very variable; therefore this parameter should not be used for graded evaluation of individual scientists or research groups. At higher aggregate levels (large institutes etc) bibliometric indicators may, as part of a more general evaluation, give relevant information about research activity, provided due corrections are made for variable research field effects. The journal impact factor, i e the mean citation frequency of all articles in a journal, has been suggested as a rapid indicator of article quality. However, the distribution of citation frequency values within a journal is extremely broad and skewed; therefore assigning the same value to all articles would not seem to serve the purpose of evaluation particularly well. Furthermore the citation frequencies of articles published by individual authors or research groups are found to correlate extremely poorly with the corresponding journal impact factors. The latter parameter would thus appear to be unsuitable as an indicator of scientific quality. PMID- 2594500 TI - [Scandinavian drug cooperation, information and the European Economic Community]. PMID- 2594501 TI - [Prevention of attempted suicide among young people]. AB - An increasing number of young people in the Nordic countries try to commit suicide. Some of these attempts could perhaps be prevented if there was widespread knowledge of several characteristic features of such youngsters, and if we sought to give them attention and assistance. PMID- 2594502 TI - Unnecessary tragedies. PMID- 2594503 TI - The best policy? PMID- 2594504 TI - Fat facts. PMID- 2594505 TI - Crisis of confidence. PMID- 2594506 TI - Breath of life. PMID- 2594507 TI - Equality for whom? PMID- 2594508 TI - Little white lies. PMID- 2594510 TI - Fat at forty but getting fitter. PMID- 2594509 TI - Schizophrenia: the family approach. PMID- 2594511 TI - Making sense of episiotomy. PMID- 2594512 TI - Small change. PMID- 2594513 TI - Goodwin's goodbye. Interview by Toni Turner. PMID- 2594515 TI - Good home offered. PMID- 2594514 TI - 'Swimming upstream'. PMID- 2594516 TI - Working on the edge. PMID- 2594517 TI - Guidelines for nurses on safe practice with cytotoxics. PMID- 2594518 TI - Serving the civil servants. PMID- 2594520 TI - Holding the baby. PMID- 2594519 TI - A midwife for women with diabetes. PMID- 2594521 TI - The first ten days. PMID- 2594523 TI - As others see us. Moving with the times. PMID- 2594524 TI - Care of the mind. PMID- 2594522 TI - Enrolled nurses. Quick conversion. PMID- 2594525 TI - Patient satisfaction. PMID- 2594526 TI - Systems of life No. 177. Senior systems--42. PMID- 2594527 TI - Anxiety in a coronary care unit. PMID- 2594528 TI - Mental handicap nursing. PMID- 2594529 TI - Mental handicap nursing. Service with a smile. PMID- 2594530 TI - Mental handicap nursing. Centres of excellence. PMID- 2594533 TI - Integrating mental health with general health care nursing. PMID- 2594532 TI - Nursing: born out of great struggle and hardships. PMID- 2594531 TI - Mental handicap nursing. Double stigma. PMID- 2594534 TI - Subarachnoid haemorrhages. PMID- 2594535 TI - The thirty-five golden eye rules. PMID- 2594536 TI - Health status of nurses and yoga. I. Baseline data. AB - In this ongoing ICMR project on "Effect of Yoga on the Health of Nurses", some baseline data on the health of nurses of Nehru Hospital, P.G.I., Chandigarh are reported. This was obtained before the start of yoga therapy in selected cases and collected with the help of six psychological tools. Out of a total of 501 nurses, 452 (90.2%) could be contacted and studied. Mean age was 30.43 years and mean years of service 9.93 years. Mean scores on the psychological tests indicated poor health status of nurses, average neuroticism, depressive tendencies and role stress. Sense of Well-Being was high in them. The data is discussed in the light of researches in this area. This is the first of a series of three articles to be published in the Journal. PMID- 2594537 TI - Child feeding schedule: a study in the framework of integrated child development services. PMID- 2594539 TI - Invisible nurses. PMID- 2594538 TI - The schizophrenic patient: a study of family members' understanding. PMID- 2594540 TI - New 800 number for AIDS information clearinghouse. PMID- 2594541 TI - Modeling the key AIDS virus enzyme: implications for antiviral therapy. PMID- 2594542 TI - Acral erythema during bone marrow transplantation: a case study. AB - Six of 13 patients receiving high-dose cytosine arabinoside as preparation for bone marrow transplant experienced painful redness and blistering of the hands and feet. Literature reports described this syndrome in patients receiving high dose chemotherapy but at lower rates of occurrence than in this series of patients. Nursing problems encountered in patients experiencing acral erythema included: pain, compromised self-care, decreased activity, and infection potential. Nursing measures for dealing with these problems are described. PMID- 2594543 TI - Patient teaching about hyperthermia. PMID- 2594544 TI - Maintenance of central venous catheters in children. PMID- 2594545 TI - Temporary repair of a damaged external venous access device. PMID- 2594546 TI - Guidelines for the oncology nurse when introducing VADs to the healthcare setting. PMID- 2594547 TI - Use of solid wafer skin barrier with venous access devices. PMID- 2594549 TI - Withdrawal occlusion in VADs. PMID- 2594548 TI - Implanted ports for patients with sickle cell anemia. PMID- 2594550 TI - Helping staff to maintain skills with VADs. PMID- 2594551 TI - Clinical toxicities of the combination of 5-fluorouracil and recombinant interferon alfa-2a: an unusual toxicity profile. AB - Recombinant interferon (rIFN) modulates the cytotoxic effects of the fluorinated pyrimidine, 5-fluorouracil (5FU), in in vitro experimental tumor cell systems. In three clinical trials employing rIFN and 5FU in patients with advanced colorectal carcinoma conducted at the Albert Einstein College of Medicine, more than half the patients achieved an objective response. Of interest, the clinical spectrum of toxicities observed with this combination is different from those seen with either rIFN or 5FU alone. This novel constellation of toxicities includes a clinical syndrome characterized by watery diarrhea followed by life-threatening sepsis. Thus, careful observation and characterization of these toxicities are required. Patient education, with the goal of making patients recognize serious side effects, is important in the management of these patients. PMID- 2594552 TI - The biotherapy of cancer--III. Proceedings of a symposium; May 19, 1989; San Francisco, California. PMID- 2594553 TI - The enhanced potential use of recombinant alpha interferon in the treatment of AIDS-related Kaposi's sarcoma. AB - Alpha interferon has been extensively studied in the treatment of the epidemic form of Kaposi's sarcoma (KS) common in the acquired immunodeficiency syndrome (AIDS). Its safety and efficacy against KS have been well documented, with objective tumor responses seen in 25%-50% of cases. In a number of large uncontrolled studies, patients had a low incidence of opportunistic infections (OIs) during recombinant alpha interferon therapy. Although several factors may be involved, individuals responding to interferon have a distinct survival advantage over those not responding. Patients with better prognostic features, such as CD4 (T-4/T-helper cell)* counts greater than 200/mm3, no history of OIs, and no lymphoma-like "B" symptoms, are most likely to respond to interferon. Recent studies have identified a soluble growth factor produced by human immunodeficiency virus (HIV)-infected T-lymphocytes, which may be important in the propagation of KS cells in vitro. Studies demonstrating in vivo and in vitro HIV inhibitory effects of alpha interferon and the correlation of antiviral and antitumor responses now suggest that the antiretroviral action of this agent may be critical in the control of KS. Phase I trials of interferon alpha plus the antiretroviral drug zidovudine (azidothymidine, AZT) have shown the combination to be well-tolerated and to produce anti-KS responses at lower doses of each agent than is generally administered. Synergistic antiretroviral activity has been demonstrated with zidovudine and interferon alpha in vitro. Phase II trials of this combination currently are in progress. PMID- 2594554 TI - [Correction of anterior or distal hypospadia using the Mathieu-Righini technic]. AB - In a overall series of 1621 hypospadias operated on, the Authors describe the technical aspects and report the precise indications and results in 141 cases of anterior and middle penile hypospadias using the one-stage Mathieu-Righini repair. This technique has resulted in remarkably few complications and very nice aesthetic results. There was a remarkably low (3.5%) rate of fistula and no urethral stenosis without necessity of postoperative urethral dilatations. The penis looks "normal" in appearance as well as in function. PMID- 2594556 TI - [A particular type of self management of asthma in childhood. The Neapolis project]. AB - The goal of this study was the observations of the comportment of 5 groups of asthmatic children, followed either with weekly ambulatory control of functional respiratory capacity or with daily control of PEF at home by Asses Peak Flow. The five groups were formed: group A (10 allergic subjects either to aeroallergens or to foods, with exclusion of food allergens from diet); group 1B (similar group, which executed the food allergen's exclusion with weekly reintroduction of one food allergen with protection of DSCG); group 1C (allergic children either to aeroallergens or to food, who non executed the withdrawal of food allergens from diet: Control group); 2A group (allergic children only to aeroallergens, which executed only the acarus' removal from ambient); 2B group (allergic only to foods, which executed the removal of food allergens from diet). The control's results showed near to 0, for pathology, the group 2B, then the group 1A, then 2A and 1B; the 1C group showed heavy asthmatic condition and employed beta 2-drugs and cortisonics. PMID- 2594555 TI - [Atopy, environmental pollution and respiratory function. Study of 1000 children from 2 areas of the city of Naples]. AB - The aim of this study was to observe the chronic respiratory deficiency in childhood caused by two possible motives: allergy and ambiental pollution. We executed aerial samples in two zones of Naples, one (USL 45) with heavy pollution because many factories present and other with slight pollution (USL 40). The authors calculated the PEF (Peak Expiratory Flow at the first second) and in a group of subject also the spirometric values, in two groups of subjects, one of atopic children and in the other of non atopic children. The study showed a greater number of atopic subjects with abnormal PEF in the zone with heavy pollution; in non atopic children the abnormal PEF was greater in the zone with heavy pollution (35.2%) in comparison with slight pollution zone (3%). PMID- 2594557 TI - [Sensitivity and specificity of antigliadine antibodies in the diagnosis of celiac disease in a population of children in Toscana]. AB - The aim of this study was to determine the value of IgA and IgG antigliadin antibody test (AGA) for screening, diagnosis and follow-up of coeliac disease. A rapid, simple, sensitive and accurate immunosorbent assay (ELISA) was used to determine AGA IgA and IgG in the sera of patients with untreated coeliac disease (I stage), coeliac patients in gluten withdrawal, healthy controls, children with gastroenterological disorders other than coeliac disease and children with constitutional short stature. In the I stage of coeliac disease the AGA IgA gave a sensitivity of 90.9% and a specificity of 97.9%, the IgG assay resulted in a sensitivity of 100% and a specificity of 82.3%. AGA IgG resulted positive in 17.7% of control disease group, but it's interesting to remark that they had a mean level significantly lower than in coeliac patients. On gluten free diet the titres of AGA IgA returned to normal value in three months, while the AGA IgG showed a slower decrease. PMID- 2594558 TI - [Damage of the cranio-facial system induced by food allergy]. AB - The goal of the study was demonstrate that the cranio dental deformities in the atopic subject are caused from aeroallergens but from food allergens too. In all subjects studied the Authors noted a heavy rise of RAW's values and fall of CV FEV1 and CV 25-75%; increase of basilar corner, increase of diameters of frontal, mascelar and sphenoidal sinuses, temporo-mandibular articulation' damage in comparison with normal values of normal children, from Caffey and Hasmann. PMID- 2594559 TI - [Extrapyramidal type collateral effects of the administration of metoclopramide to children]. AB - Metoclopramide (M.) is a neurolectic drug used with good results in digestive tracts disorders. Even in minimum doses Metoclopramide may cause side effects to children. The most frequent are: localized hypertonia, oculogyric fits, trismus, cervical, oral and lingual dyskinesias, tremors and agitations. Symptoms seem to be serious but it is sufficient to stop the cure that all signs fade away. Manufactures show three personal side-effects' remarks by M. and advise to administer the drug to children with more caution since they are very sensitive to the substance. PMID- 2594560 TI - [Benign intracranial hypertension during treatment with acetylsalicylic acid: presentation of 2 cases in children]. AB - The authors report two cases of benign intracranial hypertension associated to Aspirin therapy promptly regressed after withdrawal of the drug. This side effect did never described and its pathogenetic mechanism is unknown. PMID- 2594561 TI - [Computerized tomography of the skull in children with lymphoblastic leukemia treated with prophylactic cranial radiation]. AB - Thirty asymptomatic patients with acute lymphoblastic leukemia who had received prophylactic cranial irradiation (16 pts had 2400 cGy, 14 pts 1800 cGy) and intrathecal methotrexate were studied by computed tomography of the brain 60 to 148 months after initiation of prophylaxis. Three of 30 (10%) patients presented abnormal findings: widening of frontal subarachnoid space (1 patient), little area of decreased attenuation coefficient (1 patient), and intracerebral calcifications (1 patient Tomography abnormalities could be detected either in patients treated with 2400 cGy and in those treated with 1800 cGy. None of our patients showed central nervous system dysfunctions on physical examination. The results of our study suggest that tomography findings have a poor clinical significance. PMID- 2594562 TI - [The safe transportation of children in automobiles]. AB - The Author emphasizes the significant number of children who sustain fatal accidents during their transport on motor vehicles and relates the Act recently promulgated by the Italian Parliament on the mandatory use of particular restraining devices as well as safety harness for children. PMID- 2594563 TI - [Vesico-ureteral reflux and vesico-sphincteral dysfunction in children]. AB - The neurologically normal children affected by v.u. reflux frequently have miction disorders. The bladder-sphincter dysfunction can determine high intravesical pressures causing distortion of the vesico-ureteral junction in the same way of anastomotic obstruction. The urodynamic study allows the diagnosis of bladder-sphincter dysfunction and the careful therapeutic management. The medical treatment of the dysfunctional voiding may improve the evaluation of the reflux and reduce postoperatively complications and urinary tract infections. The Authors analyse their experience in the medical treatment of 40 children with vesico-ureteral reflux associated with miction disorders. The reflux resolved after medical treatment in 25% of cases and miction disorders in 50% of cases. The Authors stress the importance of careful diagnosis and treatment to improve results in this group of patients. PMID- 2594564 TI - [Possible correlations of Berger's disease and Schonlein-Henoch purpura]. AB - A case of IgA nephropathy is described. The patient had only an attack of Henoch Schonlein purpura without renal involvement when she was 7 years old. After 6 years of normal urinalysis she developed repeated bouts of gross hematuria and proteinuria. In renal biopsy typical features of Berger's disease were found. This particular case permits to debate whether the two diseases suffered by our patient were related or quite different. PMID- 2594565 TI - [Endoscopic treatment of colorectal polyps in children]. AB - In paediatric patients colorectal polyps are less frequent than in adults. In infancy, more than 70% of colorectal polyps are non-neoplastic (juvenile or amartomatous). Intestinal and pharmacological preparation are different in children with respect to adults. In infants and young children, endoscopic polypectomy is performed under general anaesthesia. From the technical viewpoint, there are no substantial differences between adult and paediatric patients. Moreover, the fact that juvenile polyps are not neoplastic in nature, generally influences the modalities of follow up. In the Division of Endoscopy of the I.N.T., from 1974 to 1987, 33 colorectal polyps were removed in 20 patients (13 M, 7 F). The age range was 2 to 14 years. Only one complication was observed: a post-polypectomy bleed, which was treated endoscopically. Histologically, there were 18 juvenile polyps, 6 hyperplastic polyps, 1 tubular adenoma; 8 polyps (6 in the same patient) were not retrieved. PMID- 2594567 TI - [Bilateral multicystic renal dysplasia. Description of a case]. AB - This is a case report of a newborn with bilateral multicystic kidney; The Authors report the etiology and the histologic features of the renal multicystic dysplasia considering the role of the sonographic examination in its precocious diagnosis. Peritoneal dialysis and renal transplantation in the first year of age are dealt about as the possible current therapeutic measures in the bilateral cases. PMID- 2594566 TI - [Facial paralysis secondary to arachnoid cysts. Description of a case in a girl with precocious puberty]. AB - Arachnoid cysts are unusual in childhood. We describe a case of arachnoid cyst in a girl with precocious puberty. The cyst caused facial paralysis from compression. A link between arachnoid cyst and precocious puberty was excluded by cerebral TAC. We briefly discuss the aetiology and topography of arachnoid cysts. PMID- 2594569 TI - [Mandibulofacial dysostosis or Franceschetti-Zwahlen-Klein syndrome: apropos of 2 cases]. AB - The Authors report two cases of mandibulofacial dysostosis: a three-months-old girl who presented with palpebral fissures in an antimongoloid direction, cleft palate, coloboma of the lower lid, hypoplasia of the malar bones and mandible, malformation of the external ears, two clefts between the mouth and left ear, minimal naso-frontal angle and a one-month-old boy who presented with similar structural deformities. These features can be considered characteristic of mandibulofacial dysostosis, whose most common finding is the presence of bilateral signs. PMID- 2594568 TI - [Peritonitis caused by meconial ileus in a very premature patient. Presentation of a clinical case]. AB - The Authors describe a case of meconium peritonitis in a low birth weight infant with associated malrotation of the intestines. We retrospectively analyzed the surgical approach during the stages of the disease. The purpose of this study is to stress a conservative surgical therapy (peritoneal cavity toilette and ileostomy), followed thereafter by intensive care, which should carefully balance metabolic and nutritional needs; it's then possible to perform a second look (canalization) only three mounths later, when a reasonable growth is achieved. A multidisciplinary approach favoured the positive outcome. PMID- 2594570 TI - [The pseudoachondroplastic form of spondyloepiphyseal dysplasia: apropos of 2 cases]. AB - The Authors report two cases of pseudoachondroplasic dysplasia observed in a child aged 2 years and 5 months and in her father 31 years old. They recall the rarity of this disease, its characteristic and radiological findings and dwell upon differential diagnosis between this rare form of condrodysplasia and achondroplasia. PMID- 2594571 TI - Persistence of atrioventricular valve regurgitation and electrocardiographic abnormalities following transient myocardial ischemia of the newborn. AB - To determine the sequelae of transient myocardial ischemia (TMI) in term infants, we reviewed clinical and investigative data in 59 infants (37 male, 22 female) with structurally normal hearts admitted over the 2-year period of 1983-1985. Twenty-three were diagnosed prior to admission as cases of birth asphyxia (5-min Apgar score less than 6), and 36 had signs of persistent fetal circulation with electrocardiographic (ECG) changes of ischemia greater than 24 h after birth. Murmurs of atrioventricular valve regurgitation (AVVR), detected in 28 patients, were confirmed in 23 of the 24 patients investigated. The murmurs resolved over a 2-day to 6-month period (median 6 days). In three patients, AVVR, left ventricular dyskinesia, and ECG anomalies persisted for 2 months (until death), 4 months, and 48 months. Initial ECGs were abnormal in 57 patients, and (of those reviewed) 60% returned to normal over a 6-day to 7-month period (median 2 months). Residual ECG anomalies included second-degree AV block and persistent ST T wave changes. Ten patients died from noncardiac causes. Neither the presence nor resolution of AVVR correlated significantly with the severity of birth asphyxia using the Apgar score, nor with the severity of the ischemic changes on the ECG. Although the cardiovascular sequelae of myocardial ischemia are usually transient, the data should prompt the need for careful review after the initial admission. PMID- 2594572 TI - Small aortic valve annulus in children with fixed subaortic stenosis. AB - Twenty-one hearts with fixed subaortic stenosis (FSAS) were examined pathologically. Thirty children with no hemodynamically significant heart disease, 31 children with valvar aortic stenosis, and 25 children with FSAS were studied by echo- and angiocardiography. The following conclusions were drawn: (1) Patients with FSAS often have abnormal aortic valve leaflets as well as small aortic valve annulus. (2) A small aortic annulus/descending aorta ratio is probably present at birth, and may decrease with increasing age. (3) In some patients with FSAS the aortic valve annulus is too small for simple resection of the fibroelastic tissue. A Konno operation is needed for these patients. (4) M mode echocardiography has not been useful in identifying abnormally small aortic valve annulus in FSAS patients. PMID- 2594573 TI - Valve replacement in children under 15 years with rheumatic heart disease. AB - From 1967 through 1984, single- or double-valve replacement for rheumatic heart disease (RHD) was undertaken in 184 children (aged 4 to 15 years) in Tunis. At the time of operation most patients were in an advanced state of cardiac disability, but most of them were still in sinus rhythm. A total of 222 valves were inserted. The most commonly used replacement valve was the Starr-Edwards caged-ball prosthesis, with 12 hospital deaths (6.5%). There were no hospital deaths among 19 children who had a (glutaraldehyde-treated porcine) xenograft replacement valve; however, a much higher rate of valve failure occurred later, owing to valve calcification (14 of 19 replacements, 11 requiring reoperation). There were 24 episodes of clinical thrombo-embolism in 21 children after insertion of a prosthetic valve, but only one in a child with a xenograft valve. Two thirds of the patients with prosthetic valves were on anticoagulants, but fewer than half of them had effective levels because of low compliance. For the group with prosthetic valves, the 10-year survival rate was 70%. PMID- 2594574 TI - Computerized tomography in occlusive infantile arteriopathy. AB - Use of computerized tomography (CT) in the diagnosis of arterial calcification of infancy, including coronary obstructive disease, has not been previously reported. We were able to demonstrate by CT scan the abnormal arteries present in this disease. The calcified arteries in this infant, who died of bowel infarction at three weeks of age, were easily delineated in CT scans of the chest, abdomen, and extremities. Autopsy sections revealed intact elastic fibers in the abnormal arteries, indicating that the basic pathologic process does not primarily involve these fibers. PMID- 2594575 TI - Congenital vertebral-jugular fistula in an infant. AB - Pediatric cardiologists are often consulted to evaluate continuous murmurs in children. This case report describes a child with a congenital vertebral-jugular fistula who presented with torticollis and a continuous murmur. The differential diagnosis of continuous murmurs in this setting is discussed. PMID- 2594576 TI - Aortic atresia with visceral situs inversus with mirror-image dextrocardia. AB - A newborn infant with situs inversus totalis (visceral situs inversus with mirror image dextrocardia) with aortic atresia is presented. No reports of this anatomical variant have previously been reported in the literature. A brief discussion of the various types of congenital heart defects and their incidence in association with situs inversus totalis is presented. PMID- 2594577 TI - Endocrine functions in atherosclerotic rabbits. AB - Radioimmunoassay of serum thyroid hormones (T3 and T4), testosterone, estradiol, insulin and cortisol of rabbits fed on a high-fat diet (coconut oil, cholesterol, cholic acid) for three months and developing experimental atherosclerosis (confirmed by biochemical tests and morphological changes in the aorta) have revealed an increase in the content of estradiol and insulin, and a decline in the level of thyroid hormones and testosterone. PMID- 2594578 TI - Preliminary pharmacological evaluation of chelidonine in rodents. AB - Our studies showed that the chelidonine administered intraperitoneally (ip) exerted an inhibitory effect on the central nervous system of the rodents. It was shown that chelidonine depressed the spontaneous and explorative motor activities, decreased body temperature, potentiated the action of hypnotics and increased sedation in reserpinized mice. Chelidonine did not affect the reactivity of the mice in the hot-plate test, and was without any protective effect against pentylenetetrazol-induced seizures. This alkaloid antagonized the head twitch response induced by 5-hydroxytryptophan (5-HTP) or 5 methoxytryptamine (5-MT) in the rat. PMID- 2594579 TI - The effect of exogenous glucocorticoids on blood adrenaline and noradrenaline during catecholaminemia induced by splanchnic nerve stimulation. AB - The effect of hydrocortisone (1 mg/kg) on the blood plasma adrenaline and noradrenaline levels was investigated in rabbits, dogs and cats during electrical stimulation (100 Hz at 80 V for 30 s) of adrenopetal segment of the splanchnic nerve. The administration of hydrocortisone increased the adrenaline retention in the circulation, which caused a significant elevation of its level in the blood plasma. In the experiments carried out on rabbits no significant difference between the effect of the same doses of corticosterone and hydrocortisone (1 mg/kg) on adrenaline level changes in the blood plasma were found. PMID- 2594580 TI - Opiate-like peptides. Part XII. Synthesis and some biological properties of Met enkephalin analogues modified in position 2 by D-alanyl residue in positions 2 and 4 by 3-(2-naphthyl)-D-alanyl residue. AB - Nine Met-enkephalin analogues containing D-alanyl residue in position 2 and/or 3 (2-naphthyl)-D-alanyl residue in positions 2 and 4 have been obtained. Their biological activity has been determined after intracerebroventricular administration to rats. Almost all compounds appeared strongly toxic causing the death of the animals. Only [D-2-Nal2,4, Met5-OMe]--enkephalin exerted an analgesic effect after the administration in the form of fine suspension. PMID- 2594581 TI - Blood coagulation changes in rats poisoned with methylmercuric chloride (MeHg). AB - The effects of methylmercuric chloride on the coagulability of blood were studied in rats. The administration of a single dose (17.9 mg Hg/kg) and a repeated dose (5 X 8 mg Hg/kg/day) of this compound resulted in hypercoagulation. The reduction of the clotting time, the increase of fibrinogen level in plasma and changes characteristic of hypercoagulation in the thromboelastographic parameters were observed. Simultaneously, signs of impaired activity of blood platelets: decreased aggregation velocity and clot retraction as well as prolongation of the bleeding time were noticed. PMID- 2594582 TI - Synthesis and pharmacological properties of phenoxyethylpiperazine derivatives. AB - Salts of new 1-phenoxyethylpiperazines 1-5, their 4-amidine derivatives 6-10 and 4-phenoxyacetyl derivatives 11-15 have been obtained. Some of them were screened for their cardiovascular activity. PMID- 2594583 TI - Rectal palpation and transrectal fine needle aspiration of the prostate in the monitoring of prostate cancer: a study of 59 patients during treatment with estramustine phosphate or estrogens. AB - Fifty-nine hormonally treated prostatic carcinoma patients were prospectively followed by rectal palpation and fine needle aspiration cytology (FNAC) at 6 month intervals for periods ranging from 6 to 120 months (median follow-up, 48 months). The cytologic impressions and palpatory findings were divided into four categories, respectively, ranging from benign to clearly malignant. Cytologic material and palpatory descriptions suitable for evaluation were available for 306 follow-up examinations, with a mean number of follow-up examinations per patient of five (range, 1-13). Tumor relapse was noted in 26 patients and was diagnosed at the same time by FNAC and palpation in six patients. In 16 of the patients tumor progression was first noted by cytology, and in four patients relapse was first detected by rectal palpation. Different patterns of cytologic and palpatory findings during the development of remission and progression of the tumors and drawbacks of the methods are discussed. PMID- 2594584 TI - Prostate epithelial cells utilize glucose and aspartate as the carbon sources for net citrate production. AB - The prostate gland (human, rat ventral prostate) has the major function of accumulating and secreting extremely high levels of citrate. This function requires unique and specialized metabolic pathways associated with prostate secretory epithelial cells by which exogenous substrates must be utilized as the six-carbon sources of citrate. Recent studies demonstrated that aspartate can serve as the four-carbon source of oxalacetate for citrate synthesis. Identification of the two-carbon source of acetyl CoA (AcCoA) had not been established. The present study investigated the probability that exogenous glucose, via pyruvate oxidation, is a physiological source of AcCoA for net citrate production by isolated epithelial cells from rat ventral prostate. Under adequate oxygenation, 5 mM glucose in the presence of aspartate plus glutamate markedly stimulated citrate production. Exogenous and endogenous pyruvate also stimulated net citrate production. We propose that glucose via aerobic glycolysis and pyruvate oxidation provides AcCoA, which condenses with oxalacetate obtained from aspartate transamination for citrate synthesis. Prostate epithelial cells do not readily oxidize citrate, which permits accumulation and secretion of the synthesized citrate. PMID- 2594585 TI - Cultured human prostate-derived fibroblasts produce a factor that stimulates their growth with properties indistinguishable from basic fibroblast growth factor. AB - Fibrostromal proliferation is believed to be important in the development of benign prostatic hyperplasia (BPH). We found that a mitogen for cultured mesodermal-derived cells was present in extracts of BPH tissue. The mitogen was identified as basic fibroblast growth factor (bFGF). Previous studies did not determine the cell population(s) responsible for bFGF production in the prostate. This information is important to the understanding of the role of bFGF in the etiology of BPH. Human prostate-derived fibroblasts (PF) were initiated in culture. Recombinant bFGF and PF lysates stimulated tritiated thymidine uptake by quiescent PF cells. Greater than 90% of the mitogen in PF lysates bound to heparin-Sepharose and had the same elution profile and apparent molecular weight as bFGF isolated from BPH tissue. The growth factor in PF lysates competed with recombinant iodinated bFGF for binding to antiserum to (1-24)bFGF. Cultured PF incorporated 35S-methionine into protein that was precipitated by antiserum to bFGF. The apparent molecular weight of the radiolabeled protein, about 17,000, was similar to authentic bFGF. The observations are consistent with the interpretation that cultured PF synthesize a growth factor that stimulates their growth with properties that are indistinguishable from bFGF. PMID- 2594586 TI - Orthopedic research: an overview of data entry, database management, and statistical analysis. AB - An orthopedic practitioner can facilitate clinical research and analyze quality assurance data with a minor investment in a personal computer, an optical scanner, and two software packages, namely a database manager and a statistics program. One of the most time-consuming stages in the research process includes entering patient chart data, editing and manipulating the data (database management), and analyzing the data (statistical analysis). This can be automated to a large extent with the above mentioned equipment. This article focuses on the steps involved in organizing an orthopedic office for research. The steps include choosing a method of data entry, choosing and implementing a database package, and choosing and implementing a statistics package. This discussion is followed by a practical review of basic statistics applicable to orthopedic research. Several simple and advanced tests are described and examples are given for each. PMID- 2594587 TI - Fractures of the femoral neck treated with cemented bipolar hemiarthroplasty. AB - Seven of 59 (12%) bipolar hemiarthroplasties for displaced femoral neck fracture were classified as failures at the 3-year follow-up examination. Two prostheses dislocated, 4 had loose femoral stems, and 1 was revised to a total hip arthroplasty because of pain. No patients developed acetabular erosion or deep infection. Only four of 15 patients examined by fluoroscopy shared movement between outer metal/cartilage and inner metal/polyethylene surfaces. All movement occurred at the outer metal/cartilage surface in the remaining nine patients. We conclude that the low failure rate, which compares favorably with the best results after internal fixation, is caused by the optimal selection of patients for this operation (high age, low activity level) and the use of bone cement. The bipolar design is less important, since most of these prostheses function as ordinary unipolar prostheses after some time. PMID- 2594588 TI - Diagnostic arthroscopy of the knee in children and adolescents. AB - There is a definite role for arthroscopy in the diagnosis and treatment of problem knees in children and adolescents. In this series, the largest reported to date, significant intraarticular pathology frequently existed in both preadolescent and adolescent groups. Three hundred ten knee arthroscopies in 285 children were reviewed. Preoperative clinical diagnoses were correlated with arthroscopic findings. In preadolescents (12 years old and younger), only 55% of preoperative clinical diagnoses were confirmed at surgery. Thirty-five percent of this group were found to have additional pathology not anticipated preoperatively. In adolescents (13 to 18 years old), 70% of clinical diagnoses were confirmed arthroscopically. Additional pathology was also found on arthroscopic examination in 25% of this group. PMID- 2594590 TI - A study of the mechanisms influencing ligament growth. AB - This study investigated the effects of tension and/or exogenous growth hormone on the growth (elongation) of ligaments. In the first experiment, tension was applied to the lateral collateral ligaments of immature rabbits. In the second experiment, a group of skeletally mature rabbits was given exogenous growth hormone while tension was applied to their lateral collateral ligaments. The results revealed that immature rabbit ligaments elongated 140 +/- 18% when tension was applied, while "control" ligaments elongated 79 +/- 5% (P less than .01). In mature rabbits receiving exogenous growth hormone, no significant change was found in the ligament's length with or without the application of tension when compared with controls. Tension applied to ligaments in immature rabbits can increase ligament growth, indicating that physical forces (tension) may be important in the regulation of ligament growth. The same tension applied to mature rabbit ligaments in combination with exogenous growth hormone did not cause a resumption of growth, indicating that tension and the presence of growth hormone are not the only factors necessary for ligament growth. PMID- 2594589 TI - Revision of painful distal tip amputations. AB - From 1968 to 1987, 22 patients were diagnosed with dysfunctioning digits after complete distal digital amputations. Each patient had the proximal portion of the partially amputated phalanx left within the injured digit. On average, 21 months after the initial injury, each patient underwent an excision of the remnant portion of the phalanx which averaged 6 mm (range 1 to 17 mm). All 22 patients reported excellent postoperative results of full function and no residual pain with an average follow up of 9 months. We theorized that localized synovitis produces joint pain related to: 1) nontolerated joint stress loading due to a change in the lever arm length of the amputated phalanx, or 2) inadequate cartilage nutrition owing to lack of stress applied to this joint. Maintaining digital length must be rethought with emphasis placed on painless function. Considering the losses to these patients in terms of time, employment, and money, a distal remnant measuring 4 mm or less should be excised, regardless of the digit, at the time of the injury. PMID- 2594591 TI - Fracture of the radial neck and proximal ulna with medial displacement of the radial shaft. Report of two cases. PMID- 2594592 TI - Nocardia osteomyelitis. Case report and review of the literature. PMID- 2594593 TI - Transphyseal fracture of the capital femoral epiphysis. PMID- 2594594 TI - Hyperthyrotrophinaemia during thyroxine replacement therapy. AB - During the follow-up of 224 cases of treated hypothyroidism, 14 clinically euthyroid patients were found to have elevated serum thyrotrophin and normal total thyroxine concentrations. Closer observation of these patients during the following 27 months resulted in the serum thyrotrophin levels returning to normal spontaneously in 8 patients (Group 1) whilst remaining elevated in 6 (Group 2), despite no significant differences in thyroid hormone levels between the two groups. Serum thyrotrophin in Group 2 patients remained high until an additional 50 micrograms/day thyroxine was prescribed although only 2 patients noted any benefit. Non-compliance or inadequate dosage of thyroxine are the probable causes of this sub-clinical hypothyroidism. Thyroid hormone estimations fail to differentiate the two conditions and we recommend a period of closer observation before making any thyroxine dosage adjustments in order to detect non-compliance. PMID- 2594595 TI - Effect of treatment with botulinum toxin on spasticity. AB - Botulinum toxin, a product of Clostridium botulinum, produces presynaptic neuromuscular block by preventing release of acetylcholine from nerve endings. The toxin was injected directly into the skeletal muscles of six patients with severe spasticity due to stroke-related hemiplegia. It produced both subjective and objective improvement. The toxin injections were well tolerated and no significant side effect was reported. PMID- 2594596 TI - Temporary transvenous cardiac pacing: 6 years experience in one coronary care unit. AB - The role of temporary percutaneous endocardial pacing has been examined in a retrospective analysis of all paced patients admitted to one coronary care unit over a 6 year period. The majority of 162 cases (84.6%) were paced for complete heart block complicating acute myocardial infarction. These patients had a higher incidence of previous hypertension, myocardial infarction and diabetes, compared to matched controls (P less than 0.05, less than 0.02 and less than 0.001, respectively). Admission blood glucose levels were also higher (P less than 0.05). The in-hospital mortality was high (46.7%), especially for those with anterior myocardial infarction (74.5%). Twenty-five (15.4%) patients without recent myocardial infarction were paced for symptomatic brady-dysrhythmias, usually due to chronic complete heart block (Lenegre's disease) or sick sinus syndrome. Most later required permanent pacing. Complications of temporary pacing were more frequent in those who died, the most common being dysrhythmias during pacemaker insertion. Review of our cases suggests that whilst facilities for temporary pacing were extremely valuable, many cases treated were not haemodynamically compromised and probably did not require pacing. Guidelines should be established on coronary care units to prevent the unnecessary morbidity, mortality and expense of the procedure. PMID- 2594598 TI - Clinical trials in elderly subjects. PMID- 2594599 TI - The relevance of anatomy and morbid anatomy for medical practice and hence for postgraduate and continuing medical education of doctors. AB - A case is presented for the durability of anatomy including dissection of the cadaver and of morbid anatomy as elements in medical education and practice. It is these subjects, as consistently relevant over the centuries for medical practice as are communication skills, that are our hallmark as doctors. It is submitted that we should take stock very carefully of their relevance to us before it is too late easily to redress the balance, given the major trends of the last two decades. PMID- 2594597 TI - Anthraquinone laxatives and human cancer: an association in one case. AB - An 18 year old girl presented with a leiomyosarcoma of the small bowel with widespread dissemination. Despite short term remissions after chemotherapy and surgery she died of the disease 10 months later. A history of prolonged exposure to danthron (an anthraquinone laxative) in childhood was obtained. Anthraquinones are known to be mutagenic and may be carcinogenic in experimental systems but danthron is not a proven carcinogen in man. The association of danthron and a rare bowel cancer in one case cannot prove a causative link. However, collection of further data seems advisable. PMID- 2594600 TI - Hepatomegaly with bull's eye calcifications. AB - A woman aged 35 years from the Philippines presented with epigastric discomfort associated with an epigastric mass. On examination the liver was markedly enlarged. PMID- 2594601 TI - Hyperkalaemic periodic paralysis: a rare presentation of Addison's disease. AB - A 44 year old man with longstanding diabetes mellitus gave a 6-month history of periodic attacks of flaccid quadriplegia. Following one of these episodes he was admitted for assessment. In view of persistent hyperkalaemia, hypoadrenalism was suspected and Addison's disease was confirmed biochemically. Adrenal replacement therapy restored the potassium levels to normal and resulted in no further attacks of paralysis. PMID- 2594602 TI - Immobilization hypercalcaemia responding to intravenous pamidronate sodium therapy. AB - A 16 year old male developed symptomatic hypercalcaemia of immobilization on day 47 following a diving accident which had resulted in incomplete C4 tetraplegia. Following initial reduction in serum calcium with salmon calcitonin 100 U/day, symptomatic hypercalcaemia recurred. A single dose of 30 mg pamidronate sodium, given intravenously, caused serum calcium to fall within 48 hours. Initial mild, asymptomatic hypocalcaemia was followed by a return to sustained normocalcaemia. No major adverse reaction was encountered, and if further clinical experience confirms its efficacy, pamidronate sodium will warrant consideration as first line therapy for immobilization hypercalcaemia. PMID- 2594603 TI - Septicaemia in a granulocytopenic patient caused by Corynebacterium striatum. AB - A 64 year old woman with metastatic endometrial carcinoma was admitted to the hospital after three grand mal seizures. Blood cultures yielded Corynebacterium striatum. The patient responded to parenteral ampicillin therapy. This is believed to be the first case of sepsis caused by this organism. PMID- 2594604 TI - Concurrent preputial calculi and penile carcinoma--a rare association. AB - A case of concurrent preputial calculi and carcinoma of the penis is reported. The causal relationship of both the lesions is still controversial and the possible common aetiopathogenesis of the entity is discussed. PMID- 2594605 TI - Oesophageal ulcer caused by warfarin. AB - Oesophageal injury is a well recognized complication of certain oral medications but warfarin has not been implicated previously. We present a case of an oesophageal ulcer occurring in a patient with mitral regurgitation taking warfarin, and demonstrate a delayed oesophageal tablet transit time. PMID- 2594606 TI - Familial pancreatic adenocarcinoma and HLA-typing. PMID- 2594607 TI - Suppression of the hepatic microsomal cytochrome P-450 dependent mixed function oxidase activities in golden hamster during Leishmania donovani infection. AB - Experimental infection of golden hamsters with Leishmania donovani caused significant alterations in the hepatic microsomal mixed function oxidase system. Gross examination of liver indicated hepatomegaly. Microsomal protein contents were only marginally elevated. Cytochrome P-450 as well as haem contents were significantly decreased and it directly correlated with the degree of infection. Cytochrome b5 exhibited elevation at lower degrees of infection which came down to control levels at the peak infection. Concomitant suppression was also noticed in cytochrome P-450 dependent monooxygenase activities, viz. aniline hydroxylase, benzo[a]pyrene hydroxylase and aminopyrine N-demethylase. No significant change was observed in NADH-cytochrome b5 reductase and NADPH-cytochrome c reductase. The results indicate suppression of hepatic microsomal MFO activities during visceral leishmaniasis. PMID- 2594608 TI - Isolation and characterization of human liver cytochrome b5 cDNA. AB - Three cDNA clones encoding human cytochrome b5 have been isolated and sequenced from a lambda gt 11 cDNA library of a human liver. The largest clone (b5-C) contains 765 base pairs corresponding to a complete coding sequence of 134 amino acids and sequences for 5' non-coding (56 bases) and 3' non-coding regions (307 bases). In Northern blots, a band hybridizing to 32P-labelled b5-B cDNA clone was detected at around 12S in mRNA of human and rat livers. The deduced amino acid sequence was identical with the partial amino acid sequence (2-100th) previously reported, except that two amino acid replacements were observed between the 89th and 91st positions. The deduced amino acid sequence of human cytochrome b5 shares 88.0, 86.5, 86.5 and 74.4% similarity with those of rat, pig, horse and chicken, respectively. The sequences in the haem binding region were highly conserved among these species. In addition, high similarities in the hydrophobicity profiles were maintained throughout their entire regions, although some diversity was observed in the N-terminal sequences between human and chicken. PMID- 2594609 TI - Trapidil derivatives and low density lipoprotein metabolism by human skin fibroblasts and by human hepatoma cell line Hep G2. AB - The effect of trapidil (RocornalR) and some of its newly developed derivatives (AR 12456, AR 12463, AR 12465, AR 12464) on the receptor-mediated low density lipoprotein (LDL) binding, uptake and degradation was studied in human skin fibroblasts (HSF) and in human hepatoma cell line Hep G2. Compound AR 12456 influenced this pathway in a selective way: it enhanced the uptake and degradation of 125I-LDL by Hep G2 cells in a dose-dependent manner, but inhibited it in HSF. Scatchard analysis of the saturable LDL binding in Hep G2 indicates that the effect of compound AR 12456 is the result of an increased number of LDL binding sites. Compound AR 12465 was less effective on LDL catabolism. Trapidil and the other derivatives were inactive under the same experimental conditions. When Ar 12456 was preincubated with Hep G2 cells and then the incubation medium was transferred to HSF, a stimulation of specific LDL pathway occurred also in this cell line. These findings suggest that a metabolite(s) of AR 12456 might be responsible for the enhanced expression of LDL receptors in cultured human cells. PMID- 2594611 TI - Participation of lipid peroxidation in the loss of hepatic drug-metabolizing activities in experimental fascioliasis in the rat. AB - Fascioliasis causes a dramatic decrease in drug-metabolizing ability of the hepatic monooxygenase (MFO) and glucuronosyltransferase (GT) enzyme systems in the rat. The present study was undertaken to determine whether lipid peroxidation is involved in the enzymatic loss. Peroxidative damage of membrane lipids (as assessed by the tissue content of malonic dialdehyde, MDA, and the diene conjugation absorption in microsomal membranes) was found to occur over the entire course of the liver infection (concomitant to a decrease in glutathione levels), and to different degrees in relation to the various steps of the parasite cycle. The onset (MDA six times the controls; delta E 1% = 1.55 at the 20th day) coincides with the beginning of the loss of MFO (-30%) and GT (-20% at the 20th day), and peaks between the 30th and 40th day (MDA eight times the controls; delta E 1% = 1.96), when the loss in the enzyme activities is maximal (MFO - 60/70%; GT - 65/95%). There was a strict correlation at all the observation times between the extent of lipid peroxidation and the decrease in drug metabolizing ability: this supports the view that lipid peroxidation is the major agent in the impairment of MFO and GT enzyme activities, and very likely in the initiation of the pathological degeneration of the liver tissue. As evidenced by histological examination, the phagocytic response of the liver tissue to the parasite invasion and growth leads to oxidative stress, which is the causative agent in the initiation and development of lipid peroxidation. PMID- 2594610 TI - Diet-induced reduction in serum lipoproteins stimulates cell proliferation in weanling rats. AB - Male weanling Wistar rats were fed a 4% cholestyramine diet and used as a model to demonstrate that a reduction in serum low density lipoproteins stimulates de novo cholesterogenesis leading to DNA synthesis and cell proliferation. Feeding this diet resulted in a decrease in serum very low density lipoproteins and low density lipoproteins, an increase in high density lipoproteins and an increase in de novo cholesterogenesis in liver, thymus, spleen, pancreas, kidney and lung. DNA synthesis increased only in the thymus and spleen. Histological examination of spleen, thymus and lymph nodes showed an increased number of immature cells and enhanced mitotic activity. These results suggest that a marked reduction in serum low density lipoproteins stimulates de novo cholesterogenesis, leading to enhanced DNA synthesis and cell proliferation. PMID- 2594612 TI - Steady-state serum concentrations of imipramine, its main metabolites and clinical response in primary enuresis. AB - Thirty-seven children (6-13 years old), receiving a flexible dosage of imipramine (IMI) for nocturnal enuresis, were evaluated. After a mean time of 8.5 +/- 7.0 weeks of therapy, 40.5% no longer wet the bed; 32.4% had a mean benefit of 80%; 27.01% had a negligible response. The best relationship observed was between clinical effect and drug serum concentrations rather than with drug daily dose, the most satisfactory being that with IMI seric values (P = 0.019). Responders (effect higher than 50%) had higher IMI serum concentrations (P less than 0.05) than poor responders. At 3 and 6 months after stopping the drug, over 90% of the responders maintained the maximum response reached during treatment. The side effects observed were irritability, reduction of appetite, headache, a mild increase of blood pressure. PMID- 2594614 TI - Protective effect of a specific platelet-activating factor antagonist, BN 52021, on bupivacaine-induced cardiovascular impairments in rats. AB - Administration of the local anaesthetic bupivacaine (1.5 or 2 mg/kg, i.v.) to rats elicited a marked decrease of mean arterial blood pressure (MBP) and heart rate (HR) leading to death (in 67% or 90% of animals respectively). Intravenous injection of the specific platelet-activating factor (PAF) antagonist BN 52021 (10 mg/kg), 30 min before bupivacaine administration (2 mg/kg i.v.) suppressed both the decrease of MBP and HR. In contrast, doses of 1 mg/kg BN 52021 given 30 min before or 10 mg/kg administered 5 min before i.v. injection of bupivacaine were ineffective. When BN 52021 (20 mg/kg i.v.) was injected immediately after bupivacaine (2 mg/kg), a partial reversion of the decrease of MBP and HR was observed, whereas the dose of 10 mg/kg was ineffective. A partial recovery of bupivacaine-induced ECG alterations was observed after pretreatment of the rats with BN 52021. Since the administration of BN 52021, at all doses studied, did not alter MBP and HR at the doses used, the bulk of these results clearly demonstrate a protective action of BN 52021, a specific antagonist of PAF, against bupivacaine-induced cardiovascular toxicity. Thus, consistent with its direct effect on heart, PAF appears to be implicated in bupivacaine-induced cardiovascular alterations. PMID- 2594615 TI - Haemodynamic effects of inosine. A new drug for failing human heart? AB - Haemodynamic effects of inosine were studied in intact dogs and subsequently in patients suffering from prolonged otherwise intractable cardiogenic shock. The nucleoside significantly improve myocardial performance in patients with an extremely low cardiac index by 63 +/- 29% as well as animals with no signs of haemodynamic deterioration, increasing cardiac output by 12.2 +/- 4.3%. These results suggest that inosine may become a promising inotropic agent. Further studies though are necessary to elucidate the mechanism of inosine action. PMID- 2594613 TI - The effect of etofibrate on cholesterol and bile acid metabolism in the hamster. AB - Hamsters were given etofibrate at a dose of 300 mg/kg body wt, by gavage for 5 days, while being fed a chow diet. After treatment, serum cholesterol levels were 27% lower compared to those of the control animals. A similar trend was observed for triglyceride levels. Hepatic lipid levels were unchanged by the treatment. HMG-CoA reductase and acylCoA cholesterol acyltransferase were decreased while cholesterol 7 alpha-hydroxylase was not significantly modified by etofibrate. A choleretic effect and an increase of cholesterol excretion into hepatic bile was observed in treated animals. Nevertheless, composition and cholesterol saturation index of gallbladder bile were similar in control and treated animals. With respect to controls, hepatic bile of treated hamsters contained a lesser amount of cholic and deoxycholic acid and a greater amount of ursodeoxycholic acid. PMID- 2594616 TI - Effect of fipexide on passive avoidance behaviour in rats. AB - The effect of fipexide, administered at different intervals after the learning trial of a single step-through type passive avoidance situation was studied. The administration of fipexide immediately after the learning trial resulted in a long-lasting facilitation of passive avoidance behaviour. On the contrary, the administration of this compound 1 h prior to the retention test failed to influence passive avoidance behaviour. The results suggest that fipexide facilitates memory consolidation but does not influence retrieval processes. PMID- 2594618 TI - Beyond the numbers game. PMID- 2594617 TI - Antitumour properties of dimethylsulphoxide ruthenium (II) complexes in the Lewis lung carcinoma system. AB - The antitumour effects of some ruthenium (II) complexes were tested in mice bearing the solid metastasizing tumour, Lewis lung carcinoma. The toxicity of trans-RuCl2 (DMSO)4 is 10-fold higher than that of its cis-isomer. Qualitatively the antitumour activity of these two complexes is comparable, although trans isomer is more potent. Both exhibit only marginal effects on primary tumour growth while significantly lowering lung metastasis formation. The effects of trans-RuCl2 (DMSO)4 on primary tumour depend on the inoculum size, being more pronounced with low tumour inocula; significant antitumour effects can be achieved also by replacing Cl with I in the molecule. trans-RuCl2(DMSO)4 markedly reduces the number of lung metastases and particularly their volume; the reduction is comparable to that obtained with equitoxic treatments of cisplatin. Treatment with trans-RuCl2(DMSO)4 for 10 consecutive days, after surgical amputation of primary tumour, significantly prolongs the survival time of the treated mice; cisplatin, at equitoxic doses, is less effective. These data show that dimethylsulphoxide ruthenium(II) complexes possess a significant antitumour and antimetastatic activity in the Lewis lung system, also exhibiting an interesting therapeutic potential when combined with surgical amputation of the primary tumour. PMID- 2594619 TI - What is a dysplastic naevus? PMID- 2594620 TI - Mitral valve prolapse syndrome, panic disorder and agoraphobia. PMID- 2594621 TI - Illness and emotional upset. PMID- 2594622 TI - CPR in the MRCGP exam. PMID- 2594623 TI - Contraception and irregular menses. PMID- 2594624 TI - The alteration of serum potassium level during sample transit. AB - A delay of only three hours between venepuncture and processing the blood can increase the level of potassium unpredictably and may be clinically significant. PMID- 2594625 TI - Shingles in general practice. AB - Patients over 50 with simple shingles should be offered topical idoxuridine or intravenous acyclovir to reduce the risk of post-herpetic neuralgia. For younger patients, specific treatment with high dose intravenous acyclovir is needed only for complications or in immunosuppressed patients. PMID- 2594626 TI - Infection as a consequence of ear piercing. AB - Infection associated with earrings is a particular problem in girls aged five to 11 years and in patients with dermatitis. Potentially fatal septicaemia due to beta-haemolytic streptococci may occur. There is a need for greater public awareness of the problem and of the potential benefit of silver jewelry. PMID- 2594627 TI - Treatment of acute major mood disturbance. AB - Depression is a common presentation in family practice, and together with mania, constitutes the group of psychiatric disorders known as major mood disturbance. There are many ways to approach these problems from classification to management. Drug treatment is thought to be more successful in the presence of biological symptoms, and the GP should be familiar with one or two drugs from each group for best effect. PMID- 2594628 TI - Preventive medicine and screening. PMID- 2594629 TI - Ethmoidal polypi. PMID- 2594630 TI - Coronary heart disease: prevention and risk factors. AB - Primary care is the ideal place to screen for coronary heart disease and to provide effective follow-up for those at risk. Nurse facilitators are available to help GPs wanting to introduce a screening service. PMID- 2594632 TI - Prison medicine. PMID- 2594631 TI - Managing rowing backs. AB - The Boat Race between Oxford and Cambridge is scheduled for the end of the month. The common injury suffered by rowers is acute back pain, and is usually a mechanical problem. It should respond to early manipulation combined with rest, ice, analgesia and a gradual resumption of exercise. PMID- 2594633 TI - Asthma related to occupation of spouse. PMID- 2594635 TI - Hypercholesterolaemia and a silent MI. AB - Results of investigations in extraordinary patients should be dealt with cautiously; it is often prudent to repeat tests. Though the aims of treatment in such cases are often the same, differences in approach to the problem are illuminating. PMID- 2594634 TI - Tamoxifen and breast cancer: indications and response. PMID- 2594636 TI - Managing the practice team. AB - Practices do not manage themselves; they need the type of leadership the GP is best placed to supply. Skills we develop in the clinical setting can be combined with practice audit to produce the ideal management stratagem. PMID- 2594637 TI - Patient contact and list size. AB - The size of a doctor's list affects the attitudes of both the doctor and his patient. Furthermore, both GP and patient satisfaction about a consultation increases with the consultation time. What is the optimal list size? PMID- 2594638 TI - Screening for colorectal cancer. AB - In this study, testing the faeces for occult blood with the Haemoccult test was well accepted by patients. Although this helped to identify those patients whose symptoms needed investigation and led to quicker diagnosis of colorectal neoplasia, the pathological staging was not improved. PMID- 2594639 TI - Acute epiglottitis in the adult. AB - GPs are often the first to see adults with acute epiglottitis, yet the information on how to treat them is not usually available. The seven cases presented here demonstrate a wide spectrum of severity with characteristic signs and symptoms. Diagnosis and management are discussed. PMID- 2594640 TI - Deputising: one practice's experience. AB - Deputising services, either commercial organisations or doctors' co-operatives, play a necessary, although not perhaps desirable, part in providing general medical services to many less privileged and high demand areas of the country. They are probably here to stay and their use appears to be increasing. This report looks at one practice's use of a deputising service. PMID- 2594641 TI - Lentigo maligna. AB - Remember to be aware of illumination and how the flash reflex may affect the final photograph. PMID- 2594642 TI - Holiday travel: planning ahead. AB - Unfamiliar physical conditions and pathogens are encountered during foreign travel. Ill effects can be avoided by careful planning and this is particularly important for the elderly, children and for travellers with chronic medical problems. PMID- 2594643 TI - Holiday travel: immunisation. AB - More people travel abroad each year, but they often receive conflicting advice about immunisation from travel agents, embassies, doctors and nurses. Published guidelines should be followed carefully to avoid risk of litigation. PMID- 2594644 TI - Common medical problems in Europe. AB - This article discusses common medical problems that might occur during a holiday in Europe and offers practical advice on prevention and management. PMID- 2594645 TI - Malaria and the traveller. AB - Malaria is a common imported infection that may present with atypical features. The failure to elicit travel history in patients presenting with febrile illness or the misinterpretation of symptoms and physical signs can delay diagnosis. PMID- 2594646 TI - Squash. AB - Squash is a game which demands physical fitness: you should be fit to play squash, not play squash to get fit. GPs may expect to see eye injuries, tennis elbow, ankle injuries and Achilles tendon ruptures. A knowledge of the nature of the game can help in the management of the problem. PMID- 2594647 TI - Is reviewing the elderly a 'good thing'? PMID- 2594648 TI - Physician, don't heal thyself: let someone else try! PMID- 2594650 TI - Efficacy of the Drionic unit. PMID- 2594649 TI - Ectopic pregnancy and the pill. PMID- 2594651 TI - The problem drinker. PMID- 2594652 TI - Intermittent testicular torsion in a 55-year-old man. PMID- 2594653 TI - A request for the 'morning-after' pill. AB - A request for post-coital contraception may be the first consultation by a young girl for contraceptive advice. The problem may be used as an opportunity to discuss other relevant issues such as AIDS. The case will need sympathetic and sensitive handling and demands consideration of confidentiality, especially in Samantha's case as she is only 15. PMID- 2594654 TI - Managing the world outside the practice. AB - Health care depends on the esteem and co-operation of many people and organisations outside the ill-defined boundary of the practice. We need to build up networks of people working in a climate of co-operation, not competition or conflict. In this way we can achieve our goals in today's turbulent environment. PMID- 2594655 TI - Renal failure in children. AB - A quarter of the children who die from renal failure could probably be saved by prompt treatment of urinary tract infections. But for all, the prognosis has been improved by dialysis, dietary manipulation, transplantation and progress in prenatal diagnosis and DNA technology. PMID- 2594656 TI - Diagnosing myalgic encephalomyelitis. AB - The diagnosis of myalgic encephalomyelitis can be difficult, particularly if laboratory evidence of infection is absent. This study compares the clinical presentation of patients with and without such evidence. Possible criteria for making a firm clinical diagnosis are discussed. PMID- 2594657 TI - Aluminium and the human brain. AB - Aluminium can cause an encephalopathy with a characteristic clinical picture and distinctive histopathology. Evidence associating aluminium with Alzheimer's disease and other dementias is both meagre and inconclusive. PMID- 2594658 TI - Finger clubbing. AB - Reflectors can be made easily and used to illuminate areas of the photograph that are in shadow, so giving the equivalent of an extra light source. Choosing the correct background guards against colour cast and distracting shadow. PMID- 2594660 TI - Viral hepatitis. AB - The prevalence of viral hepatitis reflects socio-economic conditions and may be reduced by improving hygiene and altering lifestyles. Effective prophylaxis is available for individuals who remain at high risk. PMID- 2594659 TI - Exotic diarrhoeal problems and poliomyelitis. AB - Exotic gastrointestinal infections continue to increase as world travel expands. Many are debilitating and some are life-threatening. A heightened awareness of their significance and symptomatology could help to prevent unnecessary suffering or death. PMID- 2594661 TI - HIV prevention in general practice. AB - General practice provides many opportunities for health education and for giving advice that may help prevent the spread of HIV infection. This article looks at some of the opportunities and problems. PMID- 2594662 TI - Infection/PUO on return to the UK. AB - Tropical and exotic diseases must be considered in all travellers who fall ill soon after returning home. Malaria must be aggressively excluded, regardless of whether anti-malarial prophylaxis has been taken. Other important infections include diarrhoeal disease, tuberculosis, hepatitis and sexually-transmitted diseases. PMID- 2594663 TI - Ilio-tibial band friction syndrome--a common injury. AB - Ilio-tibial band syndrome is a common sports injury in runners that is easy to recognise and treat. Unfortunately, it is infrequently diagnosed so that much unnecessary morbidity from the condition exists. PMID- 2594664 TI - Herpes ophthalmicus. AB - Always ensure that patient consent is obtained before any type of photography is undertaken, as the patient has the right to decide what is to happen to the images. PMID- 2594665 TI - An audit of epilepsy in general practice. AB - A simple records audit of patients with epilepsy revealed some deficiencies in care and that regular follow-up was inadequate. Further information was obtained by a questionnaire. A new protocol of care was introduced and further audit is being undertaken. PMID- 2594666 TI - Hypertensive care and the small practice. AB - In an audit of a protocol for the follow-up of patients treated for hypertension, it was found that satisfactory compliance to standards was met for the majority. Satisfactory results are dependent on having one person responsible for follow-up and record systems. PMID- 2594667 TI - Developing diabetic care. AB - Effective care for patients with diabetes and other chronic conditions can be achieved in general practice if goals are set and outcome measured. Clinical audit is a useful method of gathering the necessary information. PMID- 2594668 TI - Audit for all--but how? AB - Audit will soon be common-place and obligatory. The task will be difficult to perform manually but becomes simple and straightforward using the practice computer. Extensive clinical and financial audit may be easily derived from practice daily activities recorded on the computer. PMID- 2594669 TI - Dinghy sailing. AB - Sailors often have to hang outside the dinghy to hold it upright and so gain maximum speed. This puts immense strain on the knees and can lead to imbalance between the medial and lateral quadriceps leading to pain. Treatment is easy--if you know the correct exercises. PMID- 2594670 TI - Practice formularies--a weapon or a tool? PMID- 2594672 TI - What is important with pityriasis versicolor? PMID- 2594671 TI - Autologous blood transfusion. PMID- 2594674 TI - Early breast cancer detection. PMID- 2594673 TI - Asthma spoils sport for too many children. PMID- 2594675 TI - Restricted diets restrict antidepressant efficacy. PMID- 2594676 TI - A comparison of home visits. PMID- 2594677 TI - A child with nocturnal croup. AB - The domiciliary management of a four-year-old with suspected croup is difficult. The differential diagnosis ranges from relatively benign viral illnesses to acute epiglottitis and even diphtheria. Complete obstruction can occur with little warning, and the social situation may further complicate arrangements. As it is not possible to admit every patient with such symptoms, clinical judgement is vitally important. PMID- 2594678 TI - The management of change in general practice. AB - The final article in our practice management series suggests a structured approach to the management of change. PMID- 2594679 TI - Diagnosing glue ear. AB - Conventional otoscopy is a poor method of diagnosing middle ear effusions. Tympanometry is more accurate and could be used in primary health care to assess glue ear and follow up otitis media or established middle ear effusions. PMID- 2594680 TI - An alternative to termination of pregnancy. AB - Few women choose to continue a pregnancy in which the foetus is not viable. However, the decision to terminate such a pregnancy may be more traumatic for some women and their partners than allowing nature to take its course. PMID- 2594681 TI - Integrated health work with 'the new family'. AB - In this Copenhagen practice couples receive antenatal and postnatal care in group sessions. The health care professionals believe they provide a better service. Parents learn from shared experiences and benefit from the social network that is established. PMID- 2594682 TI - The White Paper and the elderly. AB - If government proposals for primary care are fully implemented, there will be a conflict between the requirement to seek out illness in elderly patients and the ability to deliver treatment. Budget holding practices may have particular problems and the government's intention that patients should have greater choice may be jeopardised. PMID- 2594683 TI - Quantitative whole-body autoradiographic determination of tacrine tissue distribution in rats following intravenous or oral dose. AB - Tacrine (1,2,3,4-tetrahydro-9-acridinamine) has been employed in diverse clinical situations but has recently been of considerable interest for the treatment of cognitive deficits associated with senile dementia (Alzheimer's disease). The present studies examined tissue distribution of radiolabeled tacrine by quantitative whole-body autoradiography. Tacrine radioequivalents were widely distributed to tissue following iv or peroral dose, with an apparently prolonged absorption phase following po dose. The presence of high levels of activity in kidneys and ureters indicates a major role for urinary excretion, but there is also evidence for biliary excretion and direct secretion of compound or metabolites into the intestinal lumen. Tacrine was rapidly taken up into the brain and demonstrated regional localization to cortex, hippocampus, thalamus, and striatum. Although the inhibition of acetylcholinesterase by tacrine is well documented, regional uptake in brain did not correlate consistently with distribution of the enzyme, supporting suggestions by others that the alleged action of tacrine in treatment of senile dementia may be by mechanisms other than cholinesterase inhibition. PMID- 2594684 TI - Analysis of drug penetration through the skin by the two-layer skin model. AB - A diffusion model for the skin penetration of drug in the finite-dose system was developed considering the skin to be composed of two layers, the outermost layer (stratum corneum) and the lower layer (viable epidermis and dermis). Based on this skin model, the Laplace transforms of the equations for the drug amounts in the receptor, the vehicle, and the skin were derived. The penetration profiles of 6-mercaptopurine (6-MP) through the intact and stripped guinea pig skin were obtained from in vitro diffusion experiments. The computer fitting of those profiles to the Laplace-transformed equations by a nonlinear least-squares program based on a fast inverse Laplace transform algorithm [MULTI-(FILT)] gave parameters such as diffusion coefficients of 6-MP and thicknesses of both layers. The mean transit time (MTT) for each diffusion process was defined based on statistical moment concept and calculated using the obtained parameters. Under the present condition, the process to move from the vehicle to the stratum corneum is demonstrated to have the longest mean time in overall processes of 6 MP penetration. PMID- 2594685 TI - Design and in vitro evaluation of dapsone-loaded micropellets of ethyl cellulose. AB - A controlled-release dosage form was manufactured by dispersing ethyl cellulose sol in acetone into a medium of mineral oil. Dapsone was used as the model drug. The powdered drug was dispersed in the ethyl cellulose sol, and the formulation variables affecting the production of the discrete and spherical micropellets and their size distribution were investigated. The percentage of SPAN 80 in the formulation affected the yield and physical properties of the micropellets. The in vitro drug release followed first-order diffusion-controlled dissolution. More than 85% of the drug was released over 5 hr for all formulation batches, with delayed release over the drug dissolution profile. PMID- 2594686 TI - Assessment of skin barrier function using transepidermal water loss: effect of age. AB - To probe age-related changes in skin barrier function, transepidermal water loss (TEWL) rates have been measured in "young" (19-42 years) and "old" (69-85 years) subjects. TEWL was determined at ventral forearm skin sites, which had been occluded for 24 hr with polypropylene chambers. Baseline TEWL rates (J infinity), which showed no dependence on age, were measured for each subject before and after the experiment. Following removal of the occlusive chamber, TEWL was monitored continuously from t = 0.5 min until its return to the baseline (preocclusion) level, which was typically in the range of 2-7 g/m2/hr. Initial TEWL rates (mean +/- SD) were found to differ significantly between young (28.6 +/- 7.5 g/m2/hr; n = 26) and old (36.9 +/- 10.5 g/m2/hr; n = 18) subjects (P less than 0.01). Relaxation of TEWL to J infinity was significantly slower in the aged cohort, such that the characteristic time for diffusion of water in the stratum corneum was estimated to be (mean +/- SD) 176 +/- 59 min for the young subjects, compared to 360 +/- 76 min for the old (P less than 0.001.). Thus, the initial TEWL value following removal of occlusion is significantly greater, and the excessive stratum corneum hydration produced by occlusion is dissipated more slowly, in old skin than in young. A hypothesis to explain the slower relaxation of perturbed TEWL in old skin is proposed. PMID- 2594687 TI - Decreased transport of p-aminohippurate in renal basolateral membranes isolated from rats with acute renal failure. AB - Transport of D-glucose, p-aminohippurate (organic anion), and tetraethylammonium (organic cation) was studied in the renal basolateral membrane vesicles isolated from rats with acute renal failure (ARF). ARF was induced by a single injection of uranyl nitrate. Carrier-mediated transport of p-aminohippurate, estimated under anion-anion exchange condition, was significantly decreased in basolateral membrane vesicles isolated from ARF rats. In contrast, there were no significant differences in D-glucose and tetraethylammonium uptake between normal and ARF rats. When normal basolateral membrane vesicles were incubated in vitro with uranyl nitrate, no significant inhibition in p-aminohippurate uptake was observed. These results suggest that organic anion transport is decreased in renal basolateral membranes from ARF rats, and this transport dysfunction cannot be explained by the direct interaction of uranyl nitrate with the organic anion carrier. PMID- 2594689 TI - Near-infrared spectroscopic determination of residual moisture in lyophilized sucrose through intact glass vials. AB - A rapid, noninvasive, and nondestructive method for determining moisture in sealed freeze-drying vials is described. The method, based on near-infrared spectrometry, used a novel fiber-optic diffuse-reflectance probe to make remote reflectance measurements from 1100 to 2500 nm through the bottom of glass vials. The correlation of the method to results obtained by Karl Fischer analysis was good (r2 = 0.97). The moisture content of sucrose, a common cryoprotectant, was determined with an error of 0.27% using a single sample scan. PMID- 2594688 TI - Solid surfactant solutions of active ingredients in sugar esters. AB - This paper describes the preparation of solid solutions of ciclosporin as model solubilizate in water-soluble sugar esters, which are solid, biodegradable, and nontoxic surfactants. Sugar esters were found to be excellent solubilizers for poorly water-soluble drugs such as ciclosporin. Such systems are suitable for the preparation of solid dosage forms for the purpose of oral administration. Addition of water to the solid solutions yields clear solutions of the solubilizate. PMID- 2594690 TI - Buccal absorption. III. Simultaneous diffusion and metabolism of an aminopeptidase substrate in the hamster cheek pouch. AB - The simultaneous diffusion and metabolism of the D- and L-isomers of the aminopeptidase substrate, leucine-p-nitroanilide (LPNA), were examined in vitro in the hamster cheek pouch. L-LPNA was completely hydrolyzed during diffusion across the cheek pouch, whereas D-LPNA crossed the cheek pouch intact. The metabolic barrier appeared to be localized in the epithelium of the cheek pouch. Addition of an aminopeptidase inhibitor, bestatin, to both diffusion cell reservoirs resulted in decreased hydrolysis of L-LPNA. The experimental results were analyzed with a mathematical model which was developed to describe the simultaneous diffusion and metabolism processes. Using this model it was estimated that the rate of diffusion of L-LPNA across the cheek pouch was less than the capacity of the tissue to hydrolyze L-LPNA. PMID- 2594691 TI - An unexpected pH effect on the stability of moexipril lyophilized powder. AB - Because of the limited stability of moexipril (RS-10085; 1) in aqueous solution, lyophilized parenteral formulations were evaluated as a function of pH in this study. In general, the lyophilized powder of 1 showed about two orders of magnitude less reactivity at 50 degree C than in aqueous solution at pH values below 3 or above 6. At pH 5.1, however, the lyophilized powder had maximum reactivity, with the rate actually comparable to that observed in aqueous solution. When the distribution of the two major products, diketopiperazine (DKP) 2 and ester hydrolysis analogue 3, was compared to the observed kinetics as a function of pH, it was clear that removal of water via lyophilization suppressed the spontaneous k1 cyclization process, the spontaneous k3 hydrolysis process, and the specific base-catalyzed k4 hydrolysis process. The overall spontaneous k2 cyclization process, however, was not affected by lyophilization. The latter result is accounted for by the increased equilibrium constant for the formation of the tetrahedral intermediate, To, as a result of lyophilization. This study demonstrates that stability data in solution can not be used for predicting the stability of moexipril in lyophilized powder form. PMID- 2594692 TI - Microbial models of mammalian metabolism: stereoselective metabolism of warfarin in the fungus Cunninghamella elegans. AB - Biotransformation stereoselectivity of warfarin was studied in the fungus Cunninghamella elegans (ATCC 36112) as a model of mammalian metabolism. This organism was previously shown to produce all known phenolic mammalian metabolites of warfarin, including 6-, 7-, 8-, and 4'-hydroxywarfarin, and the previously unreported 3'-hydroxywarfarin, as well as the diastereomeric warfarin alcohols, warfarin diketone, and aliphatic hydroxywarfarins. Using S-warfarin and R warfarin as substrates, and an HPLC assay with fluorescence detection to analyze metabolite profiles, the biotransformation of warfarin was found to be highly substrate and product stereoselective. Both aromatic hydroxylation and ketone reduction were found to be stereoselective for R-warfarin. Ketone reduction with the warfarin enantiomers exhibited a high level of product stereoselectivity in that R-warfarin was predominantly reduced to its S-alcohol, while S-warfarin was reduced primarily to the corresponding R-alcohol. PMID- 2594693 TI - Noninvasive sampling of biological fluids by iontophoresis. PMID- 2594694 TI - High-performance liquid chromatographic determination and pharmacokinetics of methyl N-[5[[4-(2-pyridinyl)-1-piperazinyl]carbonyl]-1H-benzimidazol-2-yl] carbamate (CDRI Compound 81-470), a new anthelmintic agent in rats. PMID- 2594695 TI - [Abbreviated equality?]. PMID- 2594696 TI - [Are child guidance centers oriented to the middle class? Consequences for psychosocial planning]. AB - The widespread opinion, that child guidance clinics were adapted to the standards of middle-class families is a prejudice. Investigations during the past 15 years have shown, that the percentage of lower-class families at least reaches the average rate of lower-class families in the west-german population. A lot of confusion concerning this question is due to certain investigations using unprecise methods and not clearly defined references. The tendency, that Child- and Adolescent Psychiatrists (working as an independent service or integrated into a multiprofessional team) are frequented slightly more often by lower-class families than child guidance clinics without doctors, is becoming increasingly evident. This however does not in our opinion justify the foundation of independent child-psychiatric-services in the first front. This would also conflict with the recommendations made by the "Psychiatry-Enquete". Instead it is advisable to integrate appropriately qualified doctors in all child guidances clinics. This kind of teamwork helps to overcome misunderstandings as well as narrow minded views and makes mutual understanding and learning possible, it improves the inevitable essential cooperation and through that ameliorates the quality of the auxiliary-service for the clients. To meet the needs of lower class clients, we have to search for new ways of thinking and coping in child guidance work and these services should be made known through professional public relation work. PMID- 2594697 TI - [Intervention-oriented diagnosis of aggressiveness in children]. AB - In the last eight years we adapted an especially new developed psychodiagnostic and training- and intervention-oriented approach for assessment of social aggressive behaviour of children in concrete situations by Petermann and Petermann (1980), directed to aggressive behaviour techniques of middle-age school-children. Our several theoretical, empirical (experimental) efforts we realized with reference to the following three aims: 1) Psychometrical and education-oriented judgment of relevant aspects of readiness of aggressive behaviour in different social situations and evaluation of aspects of necessity for training- and therapy-interventions (formation of competent social behaviour). 2) Psychometrical and intervention-related evaluation of different styles and types of aggressive social interactions (based on so called "Tyler matrix") of the child in social situations and 3) Different education-related training-techniques aimed at the reduction of inadequate aggressive behaviour strategies and the acquisition of competent social behaviour techniques and self efficacy in the practice of interaction, related to the different styles and types of aggressive interaction of the child. In our assessment and research procedures we examined about 700 children (9-11 years aged) in relation to the different aspects of clinical practice (see the three main points of our aims). The new diagnostic and intervention-oriented approach in our GDR-adaptation and standardization can be considered as suitable for the psychometric areas as well as for the several types and forms of training and/or psychotherapy for overcoming aggressive behaviour strategies in childhood. We could realize a very good differentiation between several Tyler-matrix-related types of aggressive social interaction pattern in relation to behaviour disturbed and normal pupils as well as for several results in training-related (therapy-orientated) procedures. PMID- 2594698 TI - Seven cases of trisomy 3 mosaicism in chorionic villi. AB - This paper describes seven cases of confined chorionic mosaicism with trisomy 3. The chromosomally abnormal cell line in chorionic villi was revealed in three cases at diagnostic CVS and in four cases at the evacuation of the uterine cavity after a missed abortion had been diagnosed by ultrasound. In two of these cases, the abortion occurred after apparently normal development of the fetus during the second trimester of pregnancy. An evaluation of the effect of confined chorionic mosaicism with trisomy 3 on the viability of the conceptus has been attempted. PMID- 2594699 TI - Prenatal diagnosis of Chinese homozygous alpha-thalassaemia 1 and haemoglobin H disease by analysis of alpha- and phi zeta-globin genes in chorionic villi and amniocytes. AB - Eighty-eight high-risk pregnancies, 81 for homozygous alpha-thalassaemia 1 and 7 for haemoglobin (Hb) H disease, were collected in this study. Chorionic villus sampling (CVS) was done in 63 cases and amniocentesis in 25 cases to obtain fetal cells. Southern blotting and DNA hybridization with alpha- and phi zeta-globin gene probes were used to determine the alpha-globin gene status. In two non informative families with non-deletional mutations, DNA analysis failed to rule out the affected condition, and fetal blood sampling (FBS) and Hb electrophoresis were used for the final diagnosis. In the 81 fetuses at risk for homozygous alpha thalassaemia 1, 17 (13 by CVS and 4 by amniocentesis) were affected, 30 were alpha-thalassaemia 1 heterozygotes, 19 were normal, and the remaining 15 were either normal or heterozygous. In the seven fetuses at risk for Hb H disease, one was normal, three were alpha-thalassaemia 1 heterozygotes, two were alpha thalassaemia 2 heterozygotes, and one was affected with Hb H disease and developed hydrops fetalis. DNA analysis on fetal cells enabled us to diagnose prenatally severe alpha-thalassaemias, to prevent the birth of infants with Hb H disease, and to minimize maternal obstetrical complications from harbouring a fetus with Hb Bart's hydrops fetalis. PMID- 2594700 TI - Community attitudes to cystic fibrosis carrier testing in England: a pilot study. AB - Inexpensive and accurate carrier testing for cystic fibrosis (CF) will be possible in the near future. There are no existing studies on the attitudes of English persons in the community to carrier testing for CF or any other recessive disorder. We have conducted a trial study of 166 persons at two schools, two doctors' surgeries, and a family planning clinic. Only a minority had clear pre existing knowledge of cystic fibrosis and its genetic nature. However, over 80 per cent of those questioned expressed interest in knowing their carrier status. Although it is well known that uptake can only be assessed when a service is in place, and while further studies are required to confirm that testing will be of interest to couples of reproductive age with no previous knowledge of CF, the data strongly suggest that there will be interest in community-wide testing for CF carrier status when such a test becomes available in the United Kingdom. PMID- 2594701 TI - Dilatation and evacuation is a preferable method for mid-trimester genetic termination of pregnancy. PMID- 2594702 TI - Prospective study on trisomy 18 and fetal choroid plexus cysts. PMID- 2594703 TI - [Pathogenetic aspects of chondrocalcinosis of the knee joint meniscus]. PMID- 2594704 TI - [Standardized patho-anatomic documentation of findings on forms from the German Society of Tumor Centers for malignancies of the mouth, jaw and face]. PMID- 2594705 TI - [Abstract paintings and the world of the microscope]. PMID- 2594706 TI - [Work capacity of patients with sarcoidosis of the respiratory organs]. AB - The results of examination of 92 patients with sarcoidosis of the respiratory organs by a medical and labor examination commission were analyzed and it was shown that the majority of the patients (85.9 per cent) had no signs of permanent loss of the working ability. However, shortcomings in the work on diagnosing the disease resulted in late hormonal therapy of the patients and brought difficulties in drawing the conclusion on their working ability since the positive time course of pulmonary lesions was not sufficient because of short term hormonal therapy. Permanent loss of the working ability resulted from progressing and generalized sarcoidosis, pronounced functional impairment of the cardiopulmonary system and unfavourable labor conditions. PMID- 2594707 TI - [Work capacity expert testimony and increase of rehabilitation possibilities in patients with urologic tuberculosis]. AB - Under the present conditions, improvement of the procedures for labor rehabilitation of patients and invalids remains one of the main tasks of social maintenance. Automatization and integrated mechanization of industrial processes improve labor conditions and decrease the level of energy required from a working person. At the same time specialized examination commissions in their practical work follow the methodical literature containing a number of obsolete propositions which markedly lower possibilities of social and labor rehabilitation of phthisiourological patients. The use of additional data defining concretely the reserve capacities of a patients with nephrophthisis having a single functioning kidney allows one to extend the degree of participation of phthisiourological patients in productive activity. PMID- 2594708 TI - [Clinical features and results of treatment in tuberculosis and chronic nonspecific lung diseases]. AB - Clinical signs of chronic nonspecific diseases of the lung and their frequency in patients with and without tuberculosis and in those with nonspecific processes are described. The treatment results in the patients with nonspecific diseases of the lung and tuberculosis are presented. PMID- 2594709 TI - [Impaired physical work capacity in patients with newly diagnosed destructive pulmonary tuberculosis complicated by bronchial obstruction]. AB - To determine tolerance of new cases of destructive pulmonary tuberculosis to physical loading and to show dependence of their physical working capacity on severity of bronchial obstruction, 78 patients were examined. It was revealed that the working capacity did depend on severity of bronchial obstruction. The highest decrease in the physical working capacity was observed in the patients with obstruction of the large bronchi and generalized obstruction. PMID- 2594710 TI - [Acute pneumonia in persons with residual tuberculous lesions]. AB - To elucidate the role of pneumonia in pathogenesis of reactivation of residual tuberculous lesions, time courses of clinicoroentgenological and immunological indices for a period of 3 to 5 years before detection of active tuberculosis were studied. Nonspecific bronchopulmonary aggravations progressing by the type of acute, persisting or abscessing pneumonia have many features providing their consideration as nonspecific "masks" of the specific process progression. The features are: localization, clinical picture, disease process, time course increasing of the host specific sensitization, hyperergic character of reactions to intracutaneous tests with tuberculin and BCG vaccine, signs of specific endobronchitis, no effect of nonspecific treatment and favourable time course of the process under the effect of specific antibacterial therapy. PMID- 2594711 TI - [Immediate and long-term results of the treatment of patients with lung abscess]. AB - The immediate results of conservative (116 subjects) and surgical (37 subjects) treatment of patients with lung abscesses were studied and the remote outcomes were followed up for periods of 1 to 8 years in 104 therapeutically treated and 33 surgically treated patients. 13.7 and 40.4 per cent of the patients, respectively, were discharged from the hospital after complete and clinical recovery. In 41.6 per cent of the patients, chronic abscesses were stated. 4.3 per cent of the patients died. After the surgical treatment postoperative complications were observed in 51.3 per cent of the patients, fatal outcomes were stated in 10.8 per cent and 21.7 per cent of the patients were qualified as invalids. In the remote periods complete and clinical recovery was stated in 26.8 and 52.8 per cent of the patients respectively, 4 (4.1 per cent) patients died and 7.4 per cent of the patients previously engaged in manual work and 3.0 per cent of the patients previously engaged in mental work were qualified as permanent invalids. PMID- 2594712 TI - [Incidence of pulmonary tuberculosis associated with chronic alcoholism and a complex treatment of those diseases]. AB - It was shown that the prevalence of alcoholism among pulmonary tuberculosis patients was high and the outcomes of both the diseases proceeding in the presence of lowered immunity were often unfavourable, including the results of long-term follow-ups. The use of a specially constructed instrument for investigating the neurodynamic characteristics of the cerebral cortex and determination of gamma-glutamyl transpeptidase in the serum promoted diagnosis of prenosological entities of alcoholism. Higher efficacy of alcoholism treatment in the patients with tuberculosis was achieved with narcotic psychotherapy using the mixture of nitrous oxide and oxygen, esperal implantation and application of rifusal, a new preparation, as well as application of extracorporeal hemosorption and enterosorption for eliminating the intoxication. Higher efficacy of tuberculosis treatment in the alcoholic patients was achieved with intravenous drop-wise infusion of antituberculous drugs along with other routes of administration. For increasing the cellular immunity, the patients were treated with chlorophylliptum or T-activin. Continuation of the complex antialcoholic and antituberculous treatment of outpatients along with simultaneous observation by phthisiologists and narcologists provided higher results. PMID- 2594713 TI - [Diseases of the internal organs in patients with bone and joint tuberculosis]. AB - By the sanatorium data, tuberculosis of bones and joints was shown to be more frequent in older persons. The treatment and rehabilitation of the patients were complicated by concomitant diseases. There was a certain relationship between the concomitant diseases and localization and severity of the tuberculosis process. Cardiovascular affections were the most frequent concomitant diseases. High therapeutic efficacy was defined by combined measures and sufficiently long-term treatment in specialized sanatoria. PMID- 2594714 TI - [Instructions on the use of tuberculin tests]. PMID- 2594715 TI - [Significance of residual lesions after healing of primary tuberculosis in the reactivation of tuberculosis process in inhabitants of rural areas of the Extreme North]. PMID- 2594716 TI - [Chronic nonspecific diseases of the lungs in patients with tuberculosis of the respiratory organs]. PMID- 2594717 TI - [Aerodynamic theory of vesicular respiration]. PMID- 2594718 TI - [Quantitative determination of isoniazid and rifampicin in the urine of patients treated with combination of drugs]. PMID- 2594719 TI - [Cases of death in outpatients with tuberculosis of the respiratory organs]. PMID- 2594720 TI - [Method of drainage of medium and small caverns in the lungs]. PMID- 2594721 TI - [Differential diagnosis and treatment of giant tuberculous caverns of the lungs simulating spontaneous pneumothorax]. PMID- 2594722 TI - [Acute isoniazid poisoning]. PMID- 2594723 TI - [Cure of advanced associated tuberculosis of 2 extrapulmonary sites]. PMID- 2594724 TI - Molecular cartography of proteins: surface relief analysis of the calf eye lens protein gamma-crystallin. AB - Methods of calculating the protein molecular surface and different map representations are described. The maps are obtained by projection of the space filling molecular model on the surface of the ellipsoid of inertia. A new approach to surface analysis is proposed which is based on the use of three general maps: an identification map with all residues outlined, a surface relief map and a coloured map with a specific colour for each of the surface atoms. Superposition of these maps greatly simplifies molecular surface analysis. The usefulness of such an approach has been demonstrated by the study of the relief of the calf eye lens protein gamma-crystallin II. Protrusions of the relief have been shown to be occupied generally by charged residues, but in some cases by the hydrophobic ones. It is interesting to note that in crystal medium the protruding residues are involved, in the majority of cases, in intermolecular contacts. The protruding regions have been found to be pseudosymmetrical to each other in accordance with the two-fold rotation axis of the molecule. However, the colours of these regions, i.e. the atoms of the corresponding side chains, differ greatly. PMID- 2594725 TI - Second structure determinations. PMID- 2594726 TI - The structure of interfaces between subunits of dimeric and tetrameric proteins. AB - The structures of the interfaces of nine dimeric and nine tetrameric proteins have been analyzed and have been seen to follow general principles. These interfaces are combinations of four structural motifs, which resemble features of monomeric proteins. These are: (i) extended beta sheet; (ii) helix-helix packing; (iii) sheet-sheet packing; and (iv) loop interactions. Other common structural features in the interfaces studied are two-fold symmetry, charged hydrogen bonds and channel formation (found only in tetramers). Monomer-monomer interfaces are intermediate in hydrophobicity and charge between the interfaces between secondary structures of monomeric proteins and the exteriors of monomeric proteins. A typical interface has one of the first three of the structural motifs at its centre and loop interactions around the outside, where most of the charge resides. PMID- 2594727 TI - A prediction of tertiary structures of peptide by the Monte Carlo simulated annealing method. AB - The Monte Carlo simulated annealing method has been applied to the prediction of three-dimensional structures of enkephalin. The low-energy conformations obtained were classified into a few groups of similar structures, which indicates that our method is effective. New low-energy structures were identified together with previously proposed structures. PMID- 2594728 TI - Stereochemical modeling of disulfide bridges. Criteria for introduction into proteins by site-directed mutagenesis. AB - A computer modeling procedure for assessing the stereochemical suitability of pairs of residues in proteins as potential sites for introduction of cystine disulfide crosslinks has been developed. Residue pairs with C alpha-C alpha distances of less than or equal to 6.5 A and C beta-C beta distances of less than or equal to 4.5 A are chosen for geometrical fixation of S atoms using the program MODIP. The stereochemistry of the modeled disulfides is evaluated using limits for the structural parameters of the various torsion angles and S-S bond length in the disulfide bridge. The ability of the procedure to correctly model disulfides has been checked with examples of cystine peptides of known crystal structures and 103 disulfide bridges from 25 available protein crystal structures determined at less than or equal to 2 A resolution. An analysis of results on three proteins with engineered disulfides, T4 lysozyme, dihydrofolate reductase and subtilisin, is presented. Two positions for the introduction of 'stereochemically optimal' disulfides are identified in subtilisin. PMID- 2594729 TI - Debrisoquine oxidation phenotype in psychiatric patients. PMID- 2594730 TI - Detection of populations at risk using drug monitoring data. PMID- 2594731 TI - Hydroxyhaloperidol and clinical outcome in schizophrenia. PMID- 2594732 TI - Evaluation of hypothalamic dopaminergic function in patients with pituitary prolactinoma. AB - This study was carried out using a dopaminergic agonist (carbidopa plus levodopa, CD + LD) and antagonist (metoclopramide, MCP) respectively for dynamic tests to observe the variations of serum prolactin (PRL), thyrotropin (TSH) and luteinizing hormone (LH) levels in 7 normal women and 11 women with pituitary prolactinoma. It was shown that CD + LD resulted in minimal suppression of serum PRL (18.4 +/- 3.4%) in tumor patients, with this being significantly less than that in normal women (80.7 +/- 4.6%). However, similar degrees of TSH and LH suppression were observed after CD + LD in patients (23.8 +/- 4.2% and 28.2 +/- 2.1%, respectively) and in normal women (27.9 +/- 2.4% and 34.7 +/- 9.0%, respectively). MCP greatly increased PRL levels in the normal women as compared with the patients (892.1 +/- 195.3%, 16.4 +/- 6.5%), but increased TSH and LH levels were much higher in the patients than in the normal women (291.4 +/- 36.1% vs 19.9 +/- 3.3% and 96.9 +/- 7.4% vs 24.9 +/- 5.5%, respectively). It was also found that the levels of TSH or LH after MCP strongly correlated with basal PRL levels in the patients (r = 0.858, P less than 0.001 and r = 0.737, P less than 0.01, respectively). These results indicate that synthesis, turnover and release of hypothalamic dopamine are normal and the hypothalamic tone is relatively high in patients with PRL-secreting pituitary tumors. PMID- 2594733 TI - Analysis of 4628 cases in the genetic counselling clinic of PUMC Hospital. AB - An analysis of 4628 cases in the genetic counseling clinic of PUMC Hospital is reported. Althogether 966 cases (20.87%) were diagnosed as having genetic diseases, among whom were 436 cases (45.13%) with chromosome aberrations, 161 (16.67%) with inherited metabolic diseases, 111 (11.49%) with constitutional bone diseases, 103 (10.66%) with various kinds of genetic neuromuscular diseases, 109 (11.28%) with different dysmorphic syndromes, and 46 (4.76%) with different kinds of genetic dermatoses and oculopathies. 973 cases (21.02%) were suspected to suffer from some form of genetic disease, but this could not be proved due to a lack of specific diagnostic methods. 2689 cases (58.10%) were found to be unaffected by inherited diseases. Some of the experiences gained and the key role of genetic counselling in family planning are briefly discussed. PMID- 2594734 TI - Effects of pulse excimer laser irradiation on the human left ventricular wall. AB - This study was to assess the potential application of excimer lasers in the ablation of myocardium in vitro for the treatment of constant ventricular tachycardia or hypertrophic cardiomyopathy. A fresh human heart and EMG model 103 XeCl pulse excimer laser machine were used. The pulse repetition rate varied from 1 to 7 Hz. Irradiation directly on the left endocardial and epicardial walls lasted for 10 seconds and was repeated 3 times, creating 3 craters. The histological changes were examined by light microscope. Results showed very close relations between the depth or volume of vaporized craters and the pulse repetition rate on the endocardial (r = 0.9674, P less than 0.001 and r = 0.8962, P less than 0.01, respectively) and epicardial walls (r = 0.9602, P less than 0.001 and r = 0.9612, P less than 0.001, respectively). A sharp, clear border without debris or coagulating necrosis was seen under the microscope. We concluded that the pulse excimer laser, differing from Ar+ or Nd:YAG lasers, might be a powerful tool for manipulating the human ventricular wall, but more work needs to be done before it can be widely applied in the treatment of cardiovascular disease. PMID- 2594735 TI - Effects of Chinese medicinal herbs on hemorheology in diabetics. AB - There was a statistically significant increase in whole blood viscosity, plasma viscosity, erythrocyte filterability index and hematocrit in diabetics with "Qi Yin deficiency and blood stasis" syndrome. After treatment with "Yi Qi Yang Yin Hou Xue" prescription there was a statistically significant improvement in hemorheological properties and a slight decrease in fasting blood glucose. PMID- 2594736 TI - Maprotiline (Ludiomil) treatment of mental depression--a clinical report of 65 cases. AB - Sixty-five cases of mental depression were treated with maprotiline (Ludiomil), including 46 cases of endogenous depression, 18 cases of neurotic depression and 1 case of depression in association with hypertension and cerebral arteriosclerosis. Ludiomil of 50-200 mg/d was given for 4 weeks and clinical pictures evaluated weekly. Clinical results showed complete recovery in 33 cases (50%), improvement in 22 cases (34%), fair in 7 cases (11%) and poor in 3 cases (5%). Dry mouth, constipation and faintness were the commonest side effects. Seizure occurred in 1 case and skin rash in 3 cases. The authors suggest that Ludiomil at a maximal dosage of 150 mg/d can be considered a relatively safe and effective antidepressant. PMID- 2594737 TI - The role of the nucleus tractus solitarius and the locus coeruleus in the abdominal vagal pressor response. AB - The central mechanism of the pressor response induced by stimulation of the central ends of abdominal vagi (SCAV) was studied in 33 anesthetized cats. The results of the experiments showed that both electro-stimulation to part of the nucleus tractus solitarius (NTS) and SCAV caused similar rises of blood pressure. The microinjection of kainic acid into the NTS (40 mmol/L, 2 microliters) evoked a prolonged rise of blood pressure but did not affect the pressor response induced by SCAV. Electro-stimulation of the locus coeruleus (LC) also elicited a pressor effect. Kainic acid at blocking dose (40 mmol/L, 2 microliters bilaterally injected into the LC induced an increase followed by a decrease in blood pressure and markedly attenuated the SCAV's pressor response. Bilateral microinjections of phentolamine (4 micrograms/2 microliters), propranolol (2 micrograms/2 microliters) or 6-hydroxydopamine (6-OHDA, 8 micrograms/2 microliters) into LC had no significant effect on the pressor response, but atropine could markedly attenuate it. These results suggest that the pressor afferents in abdominal vagi do not terminate in but pass through the NTS and the neurons in the LC play an important role in the SCAV pressor reflex. Cholinergic transmission rather than catecholaminergic transmission in the LC may be involved in this pressor response. PMID- 2594738 TI - Pulmonary vasodilator action of ligustrazine, active principle of a traditional Chinese remedy, in rats and ferrets. AB - The action of ligustrazine on the pulmonary circulation was tested in isolated perfused rat lung in vitro and autoperfused ferret lower left lobe preparation in vivo. Ligustrazine reduced hypoxic pulmonary vasoconstriction in a dose-dependent manner. It had a lesser dilator effect on KCl-induced vasoconstriction than verapamil and a relatively small inhibitory effect on the pressor response to angiotensin II. Ligustrazine preferentially inhibited the vasoconstriction caused by hypoxia and almitrine. The increased slope and intercept of the pressure-flow line caused by hypoxic vasoconstriction was reduced to the normal range after administration of ligustrazine (4 mg). Thus ligustrazine proved to be a powerful pulmonary vasodilator; it had a relatively small depressor effect on systemic blood pressure. PMID- 2594740 TI - Observation of growth and invasiveness of human uterine cervix carcinoma cell line (CC801) in the testes of nude mice. AB - A human uterine cervix carcinoma cell line (CC801) was implanted subcapsularly in the testes of nude mice and its growth and invasiveness was observed. The results showed that the taking rate of CC801 tumor cells was 70%. Two weeks after implantation, the tumor cells were surrounded by pseudocapsule and showed no invasiveness, but 4 weeks after transplantation, they began to proliferate and to penetrate the pseudocapsule. Thereafter, the tumor cells continued to invade the neighboring tissues, causing degeneration and atrophy of seminiferous tubules at later stages. After 12 weeks, the tumor tissues occupied the whole testis. The process of invasion could be divided into 5 stages: latency, proliferation, early invasion, intermediate invasion and late invasion. The rate of lymphatic metastasis was 6.6%, but no lung metastasis was found. PMID- 2594739 TI - Autoradiographic study of the attrition of migrating schistosomula in the skin of mice. I. Mice immunized with highly X-irradiated Schistosoma mansoni cercariae. AB - The migratory pattern in naive mice of Schistosoma mansoni cercariae X-irradiated with OkR, 12kR, or 48rR has been investigated with compressed organ autoradiography. Three groups of 69 mice each were infected with 75Se-labelled cercariae. The skin at the site of infection, as well as the entire lungs and liver were removed from infected mice daily from 1-21d, on 24d, and on 28d; tissues were then processed for autoradiography. Autoradiographic analysis of migratory patterns showed that the schistosomula derived from nonattenuated cercariae passed quickly from the skin to the lungs and at a moderate rate from the lungs to the liver. Schistosomula derived from 12kR-irradiated cercariae were delayed in passing from the skin to the lungs and from the lungs to the liver, so that many remained in the lungs and died there, while only a few died in the skin or liver. Schistosomula derived from 48kR-irradiated cercariae remained mainly in the skin, rarely reached the lungs and were never found in the liver. This study indicates that immunization with 48kR-irradiated cercariae will cause no significant lesions in the lungs or liver. PMID- 2594741 TI - Computed tomography of infantile spasms. PMID- 2594742 TI - Screening of 5 monomers from total glucosides of Tripterygium wilfordii. PMID- 2594743 TI - Free floating left atrial ball thrombus in a Hong Kong Chinese. PMID- 2594744 TI - Effects of fluoride and/or trace elements on enamel solubility. AB - Various studies have shown that the solubility of dental enamel can be reduced by exposing it to metal ions in the presence of fluoride. The purpose of this study was to determine the effects of various trace metal ions at two concentrations on dental enamel solubility and fluoride uptake. The solubilities of the enamel surfaces and their fluoride concentrations were first determined. Atypical teeth were discarded. Blocks of enamel were then divided into groups of five and solutions of salts of aluminium, strontium, titanium, molybdenum and vanadium followed by fluoride (4,000 ppm) were applied. Two successive layers were then etched off, using perchloric acid. Fluoride in the enamel was determined using an ion-specific electrode system. Calcium was determined by atomic absorption spectrophotometry. The values obtained were used to calculate the thicknesses of the layers removed. The results showed that combined application of aluminium and fluoride led to a marked reduction in solubility of enamel (p less than 0.001). Application of strontium (0.01 M) and fluoride also led to a significant reduction in enamel solubility (p less than 0.01). Pretreatment with titanium solution (both concentrations), aluminium or molybdenum solutions (higher concentrations) increased fluoride uptake in comparison with the control group. Statistically significant increase in fluoride uptake was seen only in those enamels treated with titanium solution at higher concentration when compared with those treated with fluoride alone. PMID- 2594745 TI - Urinary mercury concentrations in Finnish dentists. AB - During the past few years the safety of amalgam as a dental filling material has been the subject of general public discussion. So far there has been no agreement of whether micromercurialism, a term for the symptoms caused by minute amounts of mercury released from dental fillings, exists or not. Dentists may take mercury into their bodies from amalgam in their dental fillings and from handling it while working. We therefore included determination of urinary mercury concentrations in a comprehensive medical examination programme involving 136 dentists from South-Western Finland. We investigated factors possibly related to observed levels of mercury. The factor most closely related to high urinary mercury levels was use of amalgam by the dentist. Dentists who did not use amalgam had urinary mercury concentrations similar to those in Finns not occupationally exposed to mercury. Their "normal" excretion of mercury into the urine reflected the numbers of their dental fillings made from amalgam. The urinary concentrations of mercury of the dentists who used amalgam in their work were statistically highly significantly elevated. None of the values observed was close to the upper level for safety set by the WHO. However, since only one dentist in eight who used amalgam in their work had urinary mercury levels similar to those in Finns non-exposed to mercury at work, our findings suggest that every dentist should constantly take due care when using amalgam. PMID- 2594746 TI - Dental maturity standards in southern Finland. AB - Dental maturity was studied in 248 healthy children born in Helsinki from 1968-73 and in 105 healthy children living in Turku from 1971-85. In all, 1062 panoramic radiographs of these children aged from 2.5 to 17.2 years, were examined. Dental maturity was estimated by the three methods described by Demirjian et al. (1973) and Demirjian and Goldstein (1976). The aim of the study was to produce reliable dental maturity curves for use in relation to Finnish children. In addition to data for the seven-tooth model, curves and tables for two models utilizing four teeth are also given. It is shown that all of the models work well and predict dental age reliably. PMID- 2594748 TI - Dental X-ray status of patients admitted for total hip replacement. AB - The dental status of 50 patients undergoing total hip replacement (THR) was evaluated. Fourteen of the patients had no teeth. The teeth of the remaining 36 patients were in poor condition. Decay was severe in 12. Periapical infectious foci were evident in the panoramic radiographs of 24 patients. Nearly all of the 36 patients with teeth had advanced periodontal disease, as evidenced by horizontal and vertical destruction of alveolar bone. Thirty-four of the 36 dentate patients were considered to be at risk of bacteraemia because of their dental condition. The study shows the value of preoperative dental examination and treatment of patients undergoing THR. It is not clear if prophylatic antibiotic treatment is needed when patients who have undergone THR receive dental treatment. PMID- 2594747 TI - Some local and systemic factors related to tongue inflammation. AB - As part of a larger study aimed at surveying the clinical, histological and immunohistochemical features of filiform atrophy and geographic and fissured tongue, this work presents the clinical findings of three patient groups and controls. 200 individuals were examined; 18 (9%) had atrophic tongue, 15 (7.5%) geographic tongue and 53 (26.5%) fissured tongue; further, 12 (6%) had hyperkeratotic lesions of the tongue and 102 (51%) subjects had no tongue lesions. According to the anamnestic information, patients with atrophic or geographic tongue seemed to have a stronger tendency toward allergy than subjects in other groups, while patients with atrophic tongue had more abnormalities of the heart and circulatory system. These tongue forms did not show any association with smoking or drinking habits, but hyperkeratotic lesions (leukoplakia, lichen planus, hairy tongue) of the tongue were clearly associated with moderate and heavy smoking. Atrophic, geographic and fissured tongue seem to be specific changes of the lingual mucosa; patients with these changes did not have more changes elsewhere on the oral mucosa than the controls. Patients with atrophic tongue had lowered rates of saliva secretion. Histologically, heavy inflammation was noted in fissured tongue. In geographic tongue, inflammation was moderate and in atrophic tongue often only mild. Each tongue form seems to have its own typical histological morphology. PMID- 2594749 TI - Comparison of numbers of remaining teeth from questionnaires and clinical examination. AB - The purpose of this study was to compare numbers of remaining teeth from questionnaires and clinical examination and to find out whether information collected through questionnaires is sufficiently valid for use by various institutes in national level. The group studied consisted of 255 adult patients from Savonlinna, not representative of the municipal population. Numbers of remaining teeth were determined from replies to a questionnaire by the subjects and by clinical examination by two dentists. Agreement about numbers of remaining teeth as estimated by the subjects and counted by the dentists was significant when tested using Somer's D and the t-test. Correlations between estimates by subjects and counting by dentists were high (0.98 for men and 0.99 for women). Underestimation of numbers of teeth was more common than overestimation for men and women. On the basis of the results it would seem that questionnaires can give sufficiently valid data about numbers of remaining teeth if samples are large enough. PMID- 2594750 TI - On being a scientist. Committee on the Conduct of Science, National Academy of Sciences of the United States of America. PMID- 2594751 TI - Fourier-transform mass spectrometry of large molecules by electrospray ionization. AB - The multiply charged ions produced by electrospray ionization of peptides of molecular masses up to 29 kDa have been successfully introduced into a Fourier transform mass spectrometer of unique capabilities for tandem mass spectrometry, large ion dissociation, and resolution. Electrospray ionization places an unusually high number of charges on a peptide yielding mass/charge (m/z) values of 600-1500; in this range at normal operating pressures (approximately 10(-9) torr; 1 torr = 133.3 Pa) Fourier-transform mass spectrometry resolving power is greater than 100,000. Although only 10(-7) torr pressure has been obtained with the initial interface, the resulting resolving power of 5000 makes possible the resolution of isotopic peaks of multiply charged ions. Mass measuring accuracies of a few daltons for molecular masses up to 17 kDa have also been achieved. PMID- 2594752 TI - Cloning and characterization of band 3, the human erythrocyte anion-exchange protein (AE1). AB - The human erythrocyte anion-exchange protein (band 3 or AE1) was cloned from a fetal liver cDNA library. Three overlapping clones, encompassing 3637 nucleotides, were analyzed in detail. These encode a 911-amino acid protein (Mr 101,791) and detect a single 4.7-kilobase species in human reticulocyte RNA. The corresponding gene is located on chromosome 17. The protein is similar in structure to other anion exchangers and is divided into three regions: a hydrophilic, cytoplasmic domain that interacts with a variety of membrane and cytoplasmic proteins (residues 1-403); a hydrophobic, transmembrane domain that forms the anion antiporter (residues 404-882); and an acidic, C-terminal domain of unknown function (residues 883-911). The N-terminal domain contains several conserved sections (e.g., residues 57-86, 102-164, 219-347, and 375-403), some of which may contribute to binding sites for ankyrin, protein 4.1, or protein 4.2. The membrane domain is highly conserved with the exception of a single segment (residues 543-567) that contains several sites for cleavage of the protein by extracellular proteases. Based on hydropathy analyses and the wealth of available topographical and functional data, a model is proposed in which the protein crosses the membrane 14 times. PMID- 2594753 TI - Transfection of Leishmania enriettii and expression of chloramphenicol acetyltransferase gene. AB - We report a transient expression transfection system in Leishmania enriettii. A hybrid gene containing an intergenic region of the alpha-tubulin cluster and the bacterial chloramphenicol acetyltransferase (CAT; EC 2.3.1.28) gene is expressed after transfection of L. enriettii with the hybrid plasmid. The expression of the CAT gene is dependent on the presence of sequences from the alpha-tubulin gene. The hybrid gene is also active in Leishmania braziliensis and Leishmania major. PMID- 2594754 TI - Enzymatic conversion of all-trans-beta-carotene to retinal by a cytosolic enzyme from rabbit and rat intestinal mucosa. AB - Enzymatic conversion of all-trans-beta-carotene to retinal by a partially purified enzyme from rabbit and rat intestinal mucosa was demonstrated. The enzymatic product was characterized based on the following evidence: (i) The product gave rise to its O-ethyloxime by treatment with O-ethylhydroxylamine with an absorption maximum at 363 nm in ethanol characteristic of authentic retinal O ethyloxime. High-pressure liquid chromatography (HPLC) of this derivative yielded a sharp peak with a retention time of 7.99 min corresponding to the authentic compound. The enzyme blank and boiled enzyme blank failed to show any significant HPLC peaks corresponding to retinal O-ethyloxime, retinal, or retinol. (ii) The mass spectrum of the O-ethyloxime of the enzymatic product was identical to that of authentic retinal O-ethyloxime (m/z 327: 45%, M+. and m/z 282: 100%, M- ethoxy). (iii) The specific activity of the enzymatically formed [14C]retinal O ethyloxime remained constant even after repeated crystallization. (iv) The enzymatic product exhibited an absorption maximum at 370 nm in light petroleum characteristic of authentic retinal. Furthermore, it was reduced by horse liver alcohol dehydrogenase to retinol with an absorption maximum at 326 nm in light petroleum. This retinol was enzymatically esterified to retinyl palmitate by rat pancreatic esterase with a retention time of 10 min on HPLC corresponding to authentic retinyl palmitate. Thus, the enzymatic product of beta-carotene cleavage by the partially purified intestinal enzyme was unequivocally confirmed to be retinal. PMID- 2594755 TI - Isolation and characterization of s-myc, a member of the rat myc gene family. AB - A 9-kilobase-pair clone containing a myc-related gene that we have designated s myc was isolated from a rat genomic library. The entire nucleotide sequence of the cloned DNA was determined, showing that the s-myc gene contains an open reading frame consisting of 1287 base pairs without introns. In vitro transcription-translation analysis of s-myc indicated that this gene produces a protein of approximately 50 kDa. The amino acid sequence predicted from the DNA sequence showed that the s-Myc protein is closely related to the murine N-Myc protein but lacks an acidic amino acid-rich sequence commonly present in the Myc family proteins. Studies on transfection of s-myc into rat RT4-AC tumor cells revealed that the gene produces a polyadenylylated transcript of approximately 4.7 kilobases and that its high-level expression suppresses the tumor-igenicity of RT4-AC tumor cells in nude mice. PMID- 2594756 TI - Thymine dimer formation as a probe of the path of DNA in and between nucleosomes in intact chromatin. AB - Photo-induced thymine dimer formation was used to probe nucleosome structure in nuclei. The distribution of thymine dimers in the nucleosome and recent studies of the structure of thymine dimer-containing DNA suggest that the rate of thymine dimer formation is affected by the direction and degree of DNA bending. This premise was used to construct a model of the path of DNA in the nucleosome, which has the following features. (i) There are four regions of sharp bending, two which have been seen previously by x-ray crystallography of the core particle. (ii) The DNA in H1-containing nucleosomes deviates from its superhelical path near the midpoint; this is not seen with H1-stripped chromatin. (iii) The internucleosomal (linker) DNA appears to be relatively straight. PMID- 2594758 TI - Structural dependence of the inhibition of mitochondrial respiration and of NADH oxidase by 1-methyl-4-phenylpyridinium (MPP+) analogs and their energized accumulation by mitochondria. AB - Nineteen structural analogs of 1-methyl-4-phenylpyridinium (MPP+) were studied for their capacity to inhibit the mitochondrial oxidation of NAD+-linked substrates and the aerobic oxidation of NADH in inner membrane preparations from cardiac mitochondria. In the majority of cases, a good correlation was found between the two inhibition effects monitored. A few compounds were effective inhibitors of NADH oxidase but had only marginal effects on mitochondrial respiration. From studies of their accumulation by mitochondria, it appears likely that the latter compounds are not effectively concentrated by intact mitochondria by the electrical gradient and, in part for this reason, cannot reach sufficiently high concentrations at the appropriate binding site of NADH dehydrogenase. In addition, evidence is presented that the penetration of pyridinium analogs to the inhibition site in the NADH dehydrogenase complex may also be rate limiting. The data support the thesis that, for a substituted tetrahydropyridine to be acutely neurotoxic, its pyridinium oxidation product must be actively accumulated in the mitochondria and must inhibit NADH-ubiquinone oxidoreductase in its membrane environment. PMID- 2594757 TI - Complementation of adenovirus virus-associated RNA I gene deletion by expression of a mutant eukaryotic translation initiation factor. AB - Adenovirus VA RNAs (virus-associated RNAs) are small polymerase III transcripts that are required for efficient initiation of mRNA translation late in adenovirus infection. VAI RNA prevents double-stranded RNA (dsRNA) activation of the interferon-induced protein kinase (DAI kinase). Activation of this kinase results in phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha) and correlates with inhibition of translation initiation. In this report we show growth complementation of adenoviruses harboring deletions in the VAI gene in cell lines expressing a serine-to-alanine mutant of eIF-2 alpha. This serine-to-alanine mutant is resistant to phosphorylation by DAI kinase. These results directly show that the primary function of VAI RNA in the lytic adenovirus infection is the inhibition of eIF-2 alpha phosphorylation by DAI kinase and identify eIF-2 alpha as the target that mediates the effects of DAI kinase activation. Cells that express a mutant eIF-2 alpha will enable the isolation of specific host-range mutants for other types of viruses that are defective in the ability to inhibit DAI kinase. PMID- 2594759 TI - Turnip crinkle virus defective interfering RNAs intensify viral symptoms and are generated de novo. AB - Defective interfering (DI) RNAs have been isolated from a broad spectrum of animal viruses and have recently been identified in plant virus infections. Because of their ubiquitous nature, DIs are thought to play an important role in virus replication and yields. DI RNAs have now been found in association with a natural isolate of turnip crinkle virus (TCV-B) and are generated de novo after inoculation of turnip with virus derived from cloned transcripts. DI RNA G, naturally found in the TCV-B isolate, is a mosaic molecule with 5' and 3' viral segments and a repeat of 36 nucleotides at the beginning of the 3' segment. The 5'-terminal 21 nucleotides of DI RNA G were not similar to genomic TCV sequences but did resemble sequences found at the 5' end of other small RNAs associated with TCV (satellite RNAs). DI RNA G interferes with the accumulation of TCV genomic RNA and, unlike other DI RNAs, intensifies the symptoms of its helper virus. Infection of turnip with virus derived from cloned transcripts of TCV-B resulted in de novo generation of a DI RNA, DI1 RNA. DI1 RNA differed from DI RNA G by containing exact 5' and 3' ends of TCV as well as an internal virus segment. PMID- 2594761 TI - Sequence-specific intercalating agents: intercalation at specific sequences on duplex DNA via major groove recognition by oligonucleotide-intercalator conjugates. AB - An acridine derivative was covalently linked to the 5' end of a homopyrimidine oligonucleotide. Specific binding to a homopurine-homopyrimidine sequence of duplex DNA was demonstrated by spectroscopic studies (absorption and fluorescence) and by "footprinting" experiments with a copper phenanthroline chelate used as an artificial nuclease. A hypochromism and a red shift of the acridine absorption were observed. Triple-helix formation was also accompanied by a hypochromism in the ultraviolet range. The fluorescence of the acridine ring was quenched by a stacking interaction with a G.C base pair adjacent to the homopurine-homopyrimidine target sequence. The intercalating agent strongly stabilized the complex formed by the oligopyrimidine with its target duplex sequence. Cytosine methylation further increased the stability of the complexes. Footprinting studies revealed that the oligopyrimidine binds in a parallel orientation with respect to the homopurine-containing strand of the duplex. The intercalated acridine extended by 2 base pairs the region of the duplex protected by the oligopyrimidine against degradation by the nuclease activity of the copper phenanthroline chelate. Random intercalation of the acridine ring was lost due to the repulsive effect of the negatively charged oligonucleotide tail. Intercalation occurred only at those double-stranded sequences where the homopyrimidine oligonucleotide recognized the major groove of duplex DNA. PMID- 2594760 TI - Detection of specific DNA sequences by fluorescence amplification: a color complementation assay. AB - We have developed a color complementation assay that allows rapid screening of specific genomic DNA sequences. It is based on the simultaneous amplification of two or more DNA segments with fluorescent oligonucleotide primers such that the generation of a color, or combination of colors, can be visualized and used for diagnosis. Color complementation assay obviates the need for gel electrophoresis and has been applied to the detection of a large and small gene deletion, a chromosomal translocation, an infectious agent, and a single-base substitution. DNA amplification with fluorescent oligonucleotide primers has also been used to multiplex and discriminate five different amplified DNA loci simultaneously. Each primer set is conjugated to a different dye, and the fluorescence of each dye respective to its amplified DNA locus is scored on a fluorometer. This method is valuable for DNA diagnostics of genetic, acquired, and infectious diseases, as well as in DNA forensics. It also lends itself to complete automation. PMID- 2594762 TI - Gene VI of figwort mosaic virus (caulimovirus group) functions in posttranscriptional expression of genes on the full-length RNA transcript. AB - Experimental evidence for a molecular function for gene VI of the caulimoviruses is presented. Based on experiments with the figwort mosaic virus (FMV), it appears that gene VI has a role in the posttranscriptional expression of the closely packed genes (VII and I-V), which appear on the larger, full-length RNA transcript of this virus. Gene VI with its flanking 5'/3' expression signals included as a separate plasmid during electroporation of DNA into protoplasts of Nicotiana edwardsonii shows an unusual type of transactivation of a chloramphenicol acetyltransferase (CAT) gene fused at its 5' end to a small open reading frame (gene VII) of the long 5' leader of the full-length RNA transcript of the FMV genome. The level of activity of the CAT gene is increased up to 20 fold over the activity of control plasmids when gene VI is included in the electroporation mixture. Mutagenesis of the coding portions of gene VI of pGS1 RVI, a transactivating plasmid used in the electroporation experiments, demonstrated that it was probably the polypeptide product of gene VI that was responsible for the transactivating effect. Experiments with various portions of the 5' leader of the large, full-length RNA of FMV showed that the coding region of gene VII is necessary for the transactivation event. Clones of cauliflower mosaic virus (CaMV) or FMV with intact gene VI were found to reciprocally transactivate gene VII-CAT fusions (FMV) or gene I-CAT fusions (CaMV) located downstream of the 5' leader sequences of either viral genome. PMID- 2594763 TI - A tissue-specific change in repetitive DNA in rats. AB - From a genomic library constructed from an EcoRI digest of Wistar rat brain DNA, we isolated a clone (BL-1) that gave a 0.6-kilobase restriction fragment only in brain (or lens) DNA upon Southern hybridization. The tissue-specific fragment was present in Wistar and other strains (Sprague-Dawley and Donryu) of rats regardless of their sex and age. Sequencing of the clone indicated that it is closely related to a part of the LINE 3 sequence, one of the highly repetitive sequences present throughout mammalian genomes. Polymerase chain reaction using primer sequences in the BL-1 clone indicated that it is derived from an amplified (rear-ranged) sequence, although other explanations are possible. These results suggest that there are tissue-specific changes in DNA primary structure during mammalian developmental processes. PMID- 2594764 TI - Fidelity of DNA polymerases in DNA amplification. AB - Denaturing gradient gel electrophoresis (DGGE) was used to separate and isolate the products of DNA amplification by polymerase chain reaction (PCR). The strategy permitted direct enumeration and identification of point mutations created by T4, modified T7, Klenow fragment of polymerase I, and Thermus aquaticus (Taq) DNA polymerases. Incorrectly synthesized sequences were separated from the wild type by DGGE as mutant/wild-type heteroduplexes and the heteroduplex fraction was used to calculate the average error rate (mutations per base duplication). The error rate induced in the 104-base-pair low-temperature melting domain of exon 3 of the human hypoxanthine/guanine phosphoribosyltransferase (HPRT) gene was approximately 3.4 x 10(-5) for modified T7, 1.3 x 10(-4) for Klenow fragment, and 2.1 x 10(-4) for Taq polymerases after a 10(6)-fold amplification. The error rate for T4 DNA polymerase was not more than 3 x 10(-6) error per base duplication. The predominant mutations were sequenced and found to be transitions of G.C to A.T for T4 and modified T7 DNA polymerases, and A.T to G.C for Taq polymerase. Klenow fragment induced both possible transitions and deletions of 2 and 4 base pairs. PMID- 2594765 TI - Magnitude of the solvation pressure depends on dipole potential. AB - As polar surfaces in solvent are brought together, they experience a large repulsive interaction, termed the solvation pressure. The solvation pressure between rough surfaces, such as lipid bilayers, has been shown previously to decay exponentially with distance between surfaces. In this paper, we compare measured values of the solvation pressure between bilayers and the dipole potential for monolayers in equilibrium with bilayers. For a variety of polar solvents and lipid phases, we find a correlation between the measured solvation pressures and dipole potentials. Analysis of the data indicates that the magnitude of the solvation pressure is proportional to the square of the dipole potential. Our experiments also show that the oriented dipoles in the lipid head group region, including those of both the lipid and solvent molecules, contribute to the dipole potential. We argue that (i) the field produced by these interfacial dipoles polarizes the interbilayer solvent molecules giving rise to the solvation pressure and (ii) both the solvation pressure and the dipole potential decay exponentially with distance from the bilayer surface, with a decay constant that depends on the packing density of the interbilayer solvent molecules (1-2 A in water). These results may have importance in cell adhesion, adsorption of proteins to membranes, characteristics of channel permeability, and the interpretation of electrokinetic experiments. PMID- 2594766 TI - Modeling antibody hypervariable loops: a combined algorithm. AB - To be of any value, a predicted model of an antibody combining site should have an accuracy approaching that of antibody structures determined by x-ray crystallography (1.6-2.7 A). A number of modeling protocols have been proposed, which fall into two main categories--those that adopt a knowledge-based approach and those that attempt to construct the hypervariable loop regions of the antibody ab initio. Here we present a combined algorithm requiring no arbitrary decisions on the part of the user, which has been successfully applied to the modeling of the individual loops in two systems: the anti-lysozyme antibody HyHel 5, the crystal structure of which is as a complex with lysozyme [Sheriff, S., Silverton, E. W., Padlan, E. A., Cohen, G. H., Smith-Gill, S. J., Finzel, B. C. & Davies, D. R. (1987) Proc. Natl. Acad. Sci. USA 84, 8075-8079], and the free antigen binding fragment (Fab) of the anti-lysozyme peptide antibody, Gloop2. This protocol may be used with a high degree of confidence to model single-loop replacements, insertions, deletions, and side-chain replacements. In addition, it may be used in conjunction with other modeling protocols as a method by which to model particular loops whose conformations are predicted poorly by these methods. PMID- 2594767 TI - DNA flexibility variation may dominate DNase I cleavage. AB - In a previous experimental study, we proposed that the bending and torsional stiffness of DNA display a systematic sequence dependence. Subsequently, we developed an elastic strain model to quantify the sequence dependence of the bending and torsional rigidity in terms of nearest neighbor interactions and used that model to analyze the sequence dependence of the 434 repressor binding to its operator. The analysis presented here shows that, in the absence of significant local variation of DNA secondary structure, DNase I cleavage is strongly correlated with local variation in the bending flexibility as calculated from our elastic strain model and that the agreement is also quantitatively significant. It is proposed that analysis using elastic strain models will provide a preliminary set of biochemical and chemical tools to explore the relation between DNA flexibility and the binding of other proteins. PMID- 2594768 TI - Isolation of an auxin-regulated gene cDNA expressed during the transition from G0 to S phase in tobacco mesophyll protoplasts. AB - A cDNA clone for an auxin-regulated gene was isolated from a tobacco mesophyll protoplast cDNA library by differential screening. Nucleotide, sequence analysis showed that the deduced product of the gene, which we have designated par, is hydrophilic and is composed of 220 amino acids. No significant homology to other known proteins was detected. The mRNA of the par gene is approximately 900 bases long and its accumulation was detected in cultured mesophyll protoplasts as early as 30 min after the addition of 2,4-dichlorophenoxyacetic acid to the culture medium. The par mRNA was not detected in leaves or freshly prepared protoplasts or in protoplasts in the absence of 2,4-dichlorophenoxyacetic acid. Expression of the par gene was detected at a low level in actively dividing BY-2 tobacco suspension culture cells. The conspicuous accumulation of par mRNA before the initiation of DNA synthesis in tobacco mesophyll protoplasts suggests that the par gene product could play a role in the initiation of meristematic activity in differentiated mesophyll cells. PMID- 2594769 TI - Developmental and environmental regulation of a phenylalanine ammonia-lyase-beta glucuronidase gene fusion in transgenic tobacco plants. AB - A 1.1-kilobase promoter fragment of the bean (Phaseolus vulgaris L.) phenylalanine ammonia-lyase (EC 4.3.1.5) gene PAL2 was translationally fused to the beta-glucuronidase reporter gene and transferred to tobacco by Agrobacterium tumefaciens-mediated leaf disk transformation. The distribution of beta glucuronidase activity in these transgenic plants is very similar to that of endogenous PAL2 transcripts in bean, with very high levels in petals; marked accumulation in anthers, stigmas, roots, and shoots; and low levels in sepals, ovaries, and leaves. Histochemical analysis of the spatial pattern of beta glucuronidase activity showed that the PAL2 promoter is highly active in the shoot apical meristem, the zone of cell proliferation immediately adjacent to the root apical meristem, and in the early stages of vascular development at the inception of xylem differentiation. Wounding and light evoke specific changes in the spatial pattern of beta-glucuronidase activity in stems, including induction in the epidermis. These data indicate that the PAL2 promoter transduces a complex set of developmental and environmental cues into an integrated spatial and temporal program of gene expression to regulate the synthesis of a diverse array of phenylpropanoid natural products. PMID- 2594770 TI - Structure and developmental expression of a sea urchin fibrillar collagen gene. AB - We have isolated and characterized cDNA and genomic clones that specify a Paracentrotus lividus procollagen chain. The cDNAs code for 160 uninterrupted Gly Xaa-Yaa triplets and a 252-amino acid carboxyl propeptide. Analysis of the deduced amino acid sequences indicated that the sea urchin polypeptide exhibits structural features that are characteristic of the fibril-forming class of collagen molecules. Partial characterization of two genomic recombinants revealed that the 3' end of the echinoid gene displays a complex organization that closely resembles that of a prototypical vertebrate fibrillar collagen gene. In situ and Northern (RNA) blot hybridizations established the size, time of appearance, and tissue distribution of the collagen transcripts in the developing sea urchin embryo. Collagen mRNA, approximately equal to 6 kilobases in size, is first detected in the forming primary mesenchyme cells of late blastulae where it progressively accumulates until the free swimming/feeding pluteus larval stage. Interestingly, collagen transcripts are also detected in the forming secondary mesenchyme cells of late gastrulae, and by the prism stage, their derivatives appear to be the most intensively labeled cells. PMID- 2594771 TI - Lipoprotein binding and endosomal itinerary of the low density lipoprotein receptor-related protein in rat liver. AB - The high affinity of 45Ca binding to the low density lipoprotein receptor (LDL-R) and the LDL-R-related protein (LRP) was utilized to study the subcellular distribution of these two proteins in rat liver. Like the LDL-R, LRP was manyfold enriched in rat liver endosomal membranes with a relative distribution in early and late endosomal compartments consistent with recycling between endosomes and the cell surface. The high concentration of LRP in hepatic endosomal membranes greatly facilitated demonstration of Ca-dependent binding of apolipoprotein E- and B-containing lipoproteins in ligand blots. LRP was severalfold more abundant than the LDL-R in hepatic parenchymal cells, showed extensive degradation in hepatic endosomes, and was found in high concentrations in the Golgi apparatus and endoplasmic reticulum. These data suggest a high rate of synthesis of LRP that appeared to be unaffected by treatment of rats with estradiol. The repeating cysteine-rich A-motif found in the ligand-binding domain of LRP appeared to be responsible for Ca binding by LRP, LDL-R, and complement factor C9 and accounted for immunological cross-reactivity among these proteins. Weaker ligand-blotting properties and an extraordinary susceptibility to proteolysis most likely contribute to the difficulty of detecting LRP in conventional assays for lipoprotein receptors. Our data suggest an extensive proteolytic processing of this protein and are consistent with a functional role of LRP in lipoprotein metabolism. PMID- 2594772 TI - Mitochondrial DNA sequences in single hairs from a southern African population. AB - Hypervariable parts of mitochondrial DNA (mtDNA) were amplified enzymatically and sequenced directly by using genomic DNA from single plucked human hairs. This method has been applied to study mtDNA sequence variation among 15 members of the !Kung population. A genealogical tree relating these aboriginal, Khoisan-speaking southern Africans to 68 other humans and to one chimpanzee has the deepest branches occurring amongst the !Kung, a result consistent with an African origin of human mtDNA. Fifteen cases of unrelated individuals having identical sequences in the most variable parts of the mtDNA control region were found within populations of !Kung, Western Pygmies, and Eastern Pygmies, but no cases of identity were evident among these populations. This and other evidence of geographic structuring of the mitochondrial diversity in Africa, together with knowledge of the rate of accumulation of base changes in human mtDNA, implies that the average rate at which female lineages have moved their home bases during hunter-gatherer times could be as low as 13 meters per year. The technique of enzymatic amplification and direct sequencing applied to readily collected, highly stable biological materials such as hairs makes it possible to examine with high resolution many representatives of virtually any population. PMID- 2594773 TI - Molecular basis of evolutionary adaptation at the lactate dehydrogenase-B locus in the fish Fundulus heteroclitus. AB - At the extremes of its natural distribution, populations of the common killifish Fundulus heteroclitus experience a difference of more than 15 degrees C in mean annual temperature. These populations are virtually fixed for two different codominant alleles at the heart-type lactate dehydrogenase locus (Ldh-B) which code for allozymes with different and adaptive kinetic responses to temperature. Two populations near the extremes of the species range (i.e., Maine and Georgia) were further studied for thermal adaptation at this locus. In the absence of any kinetic differences one would predict that to maintain a constant reaction velocity, 2 to 3 times as much enzyme would be required for each 10 degrees C decrease in environmental temperature. Consistent with this adaptive strategy and in addition to the adaptive kinetic characteristics, the LDH-B4 enzyme (EC 1.1.1.27) concentration and its mRNA concentration were approximately twice as great in the northern population as in the southern population. Acclimation experiments allow us to conclude that these differences are due to a combination of fixed genetic traits (evolutionary adaptation) and plastic responses to temperature (physiological acclimation). Furthermore, our calculations show that the LDH-B4 reaction velocities are essentially equivalent for these two populations, even though they live in significantly different thermal environments. PMID- 2594774 TI - Deletion of stably integrated DNA is suppressed by cadmium and zinc. AB - The bacterial xanthine-guanine phosphoribosyltransferase (GPT) gene was fused to a metal-responsive promoter and transfected into a murine cell line. Clonal transformants harboring metal-responsive or nonresponsive GPT genes (using a thymidine kinase promoter) were then studied for the loss of transfected gene function either during periods of constitutive expression or during periods of induced activity. Nontoxic levels of cadmium and zinc markedly reduced the frequency of mutagenesis in all transfected lines irrespective of transcriptional status. A survey of 17 GPT-clones derived from two original transfectants showed partial or complete excisions of the transfected gene in every case. These studies show that quantities of cadmium and zinc that induce metallothioneins also suppress the incidence of deletions in murine cells. PMID- 2594775 TI - Long-range organization of tandem arrays of alpha satellite DNA at the centromeres of human chromosomes: high-frequency array-length polymorphism and meiotic stability. AB - The long-range organization of arrays of alpha satellite DNA at the centromeres of human chromosomes was investigated by pulsed-field gel electrophoresis techniques. Both restriction-site and array-length polymorphisms were detected in multiple individuals and their meiotic segregation was observed in three generation families. Such variation was detected in all of the alpha satellite arrays examined (chromosomes 1, 3, 7, 10, 11, 16, 17, X, and Y) and thus appears to be a general feature of human centromeric DNA. The length of individual centromeric arrays was found to range from an average of approximately 680 kilobases (kb) for the Y chromosome to approximately 3000 kb for chromosome 11. Furthermore, individual arrays appear to be meiotically stable, since no changes in fragment lengths were observed. In total, we analyzed 84 meiotic events involving approximately 191,000 kb of alpha satellite DNA from six autosomal centromeres without any evidence for recombination within an array. High frequency array length variation and the potential to detect meiotic recombination within them allow direct comparisons of genetic and physical distances in the region of the centromeres of human chromosomes. The generation of primary consensus physical maps of alpha satellite arrays is a first step in the characterization of the centromeric DNA of human chromosomes. PMID- 2594776 TI - Sex-chromosomal odor types influence the maintenance of early pregnancy in mice. AB - Genetically specified body odors are termed odor types. We showed previously that both the X chromosome and the Y chromosome of the mouse determine differential odor types demonstrable by the behavior of trained mice in the conventional Y maze test system extensively used in the definition of odor types specified by the major histocompatibility complex (MHC). In the present studies we aimed to ascertain whether perception of X chromosomal and Y chromosomal odor types, like the perception of MHC odor types, exerts a spontaneous influence on reproduction. By making use of reciprocal F1 hybrid males and males of the congenic B6.YAKR strain, males differing solely in their X chromosomes, their Y chromosomes, or both were tested in the conventional pregnancy-block system in which isolated females in early pregnancy are known to be subject to a heightened incidence of failed pregnancy when confronted with the scent of a male whose MHC type differs from that of the missing stud male. As previously established for MHC disparity, perception of X chromosomal disparity or of Y chromosomal disparity between stud and secondary males caused a highly significant rise in the incidence of terminated pregnancy. Thus perception of differential odor types other than those specified by the MHC may also be concerned in aspects of selective reproduction. PMID- 2594777 TI - Description and validation of a method for simultaneous estimation of effective population size and mutation rate from human population data. AB - A method is presented for utilizing population data on electrophoretic variants of proteins to estimate simultaneously the effective sizes (Ne values) of the populations in question and the rate of mutation resulting in electromorphs at the loci whose products were surveyed. The method is applied to data from 12 relatively unacculturated Amerindian tribes for whom census data and independent estimates of the number of different electrophoretic variants at 27 loci are available. Because of tribal demographic structure, Ne should be less than the current number of reproductive-aged adults. In fact, it is substantially greater for 7 tribes, most likely due to intertribal migration and a recent decrease in tribal size. Estimates of locus mutation rates for the 27 loci vary by more than a factor of 20, with an average of 1.1 x 10(-5) per locus per generation. This latter estimate is in satisfactory agreement with the results of other indirect approaches to the estimation of mutation rates in these tribes but about two times higher than the results of direct estimates based on these same loci in studies on civilized populations. This discrepancy could be due to the above hypothesized migration and to decreases in tribal size. PMID- 2594778 TI - Urate oxidase: primary structure and evolutionary implications. AB - Urate oxidase, or uricase (EC 1.7.3.3), is a peroxisomal enzyme that catalyzes the oxidation of uric acid to allantoin in most mammals. In humans and certain other primates, however, the enzyme has been lost by some unknown mechanism. To identify the molecular basis for this loss, urate oxidase cDNA clones were isolated from pig, mouse, and baboon, and their DNA sequences were determined. The mouse urate oxidase open reading frame encodes a 303-amino acid polypeptide, while the pig and baboon urate oxidase cDNAs encode a 304-amino acid polypeptide due to a single codon deletion/insertion event. The authenticity of this single additional codon was confirmed by sequencing the mouse and pig genomic copies of the gene. The urate oxidase sequence contains a domain similar to the type 2 copper binding motif found in other copper binding proteins, suggesting that the copper ion in urate oxidase is coordinated as a type 2 structure. Based upon a comparison of the NH2-terminal peptide and deduced sequences, we propose that the maturation of pig urate oxidase involves the posttranslational cleavage of a six amino acid peptide. Two nonsense mutations were found in the human urate oxidase gene, which confirms, at the molecular level, that the urate oxidase gene in humans is nonfunctional. The sequence comparisons favor the hypothesis that the loss of urate oxidase in humans is due to a sudden mutational event rather than a progressive mutational process. PMID- 2594779 TI - Positively charged amino acid residues can act as topogenic determinants in membrane proteins. AB - When alkaline phosphatase is fused to the periplasmic domain of a cytoplasmic membrane protein, it is efficiently exported to the periplasm. Such a hybrid protein exhibits high alkaline phosphatase enzymatic activity. When alkaline phosphatase is fused to the cytoplasmic domain of a membrane protein, it remains, for the most part, in the cytoplasm. Such fusions exhibit low enzymatic activity. However, stable retention of alkaline phosphatase in the cytoplasm requires the presence in the fusion protein of the cytoplasmic loop ordinarily present in that position in the native, unfused protein. Using oligonucleotide-directed mutagenesis, we have shown that positively charged amino acids are required for the stable cytoplasmic localization of the fused alkaline phosphatase. We propose that, in addition to hydrophobic transmembrane segments, positively charged amino acids in the hydrophilic cytoplasmic domains of a membrane protein are determinants of the protein's topology. PMID- 2594780 TI - Cloning of cDNAs that encode human mast cell carboxypeptidase A, and comparison of the protein with mouse mast cell carboxypeptidase A and rat pancreatic carboxypeptidases. AB - Human skin and lung mast cells and rodent peritoneal mast cells contain a carboxypeptidase in their secretory granules. We have screened human lung cDNA libraries with a mouse mast cell carboxypeptidase A (MC-CPA) cDNA probe to isolate a near-full-length cDNA that encodes human MC-CPA. The 5' end of the human MC-CPA transcript was defined by direct mRNA sequencing and by isolation and partial sequencing of the human MC-CPA gene. Human MC-CPA is predicted to be translated as a 417 amino acid preproenzyme which includes a 15 amino acid signal peptide and a 94 amino acid activation peptide. The mature human MC-CPA enzyme has a predicted size of 36.1 kDa, a net positive charge of 16 at neutral pH, and 86% amino acid sequence identity with mouse MC-CPA. DNA blot analyses showed that human MC-CPA mRNA is transcribed from a single locus in the human genome. Comparison of the human MC-CPA with mouse MC-CPA and with three rat pancreatic carboxypeptidases shows that these enzymes are encoded by distinct but homologous genes. PMID- 2594781 TI - Sequential effects of interleukin 2-diphtheria toxin fusion protein on T-cell activation. AB - The interleukin 2-diphtheria toxin-related fusion protein (IL-2-toxin) rapidly inhibits protein synthesis in IL-2 receptor (IL-2R)-bearing phytohemagglutinin activated T cells but transiently stimulates DNA synthesis. At 7 hr after interaction with IL-2R+ phytohemagglutinin-activated T cells, IL-2-toxin-treated cells bear augmented steady-state levels of c-myc, interferon gamma, and IL-2R mRNA; these effects are indistinguishable from those produced by recombinant IL 2. Amplification of IL-2 sequences by the polymerase chain reaction reveals an increased level of IL-2 mRNA in cell cultures treated with recombinant IL-2, IL-2 toxin, and cycloheximide. These results suggest that IL-2-toxin can affect de novo IL-2 gene transcription/mRNA stabilization through independent mechanisms exerted by both the IL-2R binding domain and ADP-ribosyltransferase activity of the fusion protein. After 20 hr of culture, IL-2R mRNA was markedly decreased in both IL-2-toxin- and cycloheximide-treated phytohemagglutinin-activated T cells. Although interaction of IL-2-toxin with IL-2R+ T cells initially mimics the stimulatory effects of IL-2 upon c-myc, interferon gamma, IL-2R, and IL-2 gene expression, the consequences of inhibition of protein synthesis mediated by the ADP-ribosyltransferase activity of the toxin dominate after 7 hr and are indistinguishable from those effects mediated by cycloheximide. PMID- 2594782 TI - Procalcitonin's amino-terminal cleavage peptide is a bone-cell mitogen. AB - The parafollicular-cell (C-cell) hormone calcitonin (CT) can preserve or even augment skeletal mass by inhibiting osteoclast-mediated bone resorption. The possibility of an additional anabolic skeletal influence has also been raised: C cells might, via CT or other secretory products, affect osteoblast-mediated bone formation. The 57-residue amino-terminal procalcitonin cleavage peptide, N-proCT, has recently been identified in human and rat C cells, where it is made and secreted in equimolar amounts with CT. The coelaboration of N-proCT and CT and N proCT's sequence conservation during evolution prompted us to investigate the potential skeletal bioactivity of N-proCT. We found that synthetic human N-proCT, at nanomolar concentrations, stimulated proliferation of normal and neoplastic human osteoblasts. At maximally effective doses, human N-proCT caused more than a 100% increase above the control rate of DNA synthesis, an effect comparable to the maximal growth effect of insulin, a potent mitogen for osteoblasts. Human N proCT exerted a similar maximal mitogenic effect in chicken osteoblast cultures but at 1000-fold greater concentrations than in human bone-cell cultures. The bone-cell action of N-proCT was potentiated with insulin with a greater than 200% increase in DNA synthesis at high insulin concentrations. In sharp contrast to these findings for N-proCT, the other bioactive C-cell peptides, CT and somatostatin, showed no mitogenic effects in human or chicken osteoblast cultures. Our results indicate that the action of N-proCT on cultured bone cells is separate from and potentiated by insulin, a known growth factor. Unlike insulin and related growth factors such as insulin-like growth factor I, N-proCT is not mitogenic in skin fibroblast cultures. We propose that N-proCT is a C-cell hormone that promotes bone formation via stimulatory actions on osteoblasts and preosteoblasts. PMID- 2594783 TI - Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity. AB - Androgens act through a receptor protein (AR) to mediate sex differentiation and development of the male phenotype. We have isolated the eight exons in the amino acid coding region of the AR gene from a human X chromosome library. Nucleotide sequences of the AR gene intron/exon boundaries were determined for use in designing synthetic oligonucleotide primers to bracket coding exons for amplification by the polymerase chain reaction. Genomic DNA was amplified from 46,XY phenotypic female siblings with complete androgen insensitivity syndrome. AR binding affinity for dihydrotestosterone in the affected siblings was lower than in normal males, but the binding capacity was normal. Sequence analysis of amplified exons demonstrated within the AR steroid-binding domain (exon G) a single guanine to adenine mutation, resulting in replacement of valine with methionine at amino acid residue 866. As expected, the carrier mother had both normal and mutant AR genes. Thus, a single point mutation in the steroid-binding domain of the AR gene correlated with the expression of an AR protein ineffective in stimulating male sexual development. PMID- 2594784 TI - N-acetylation pharmacogenetics: a gene deletion causes absence of arylamine N acetyltransferase in liver of slow acetylator rabbits. AB - The New Zealand White rabbit provides a widely used animal model for the human acetylation polymorphism, which confers marked interindividual variation in the effect and toxicity of numerous drugs, chemicals, and potential carcinogens. The relationship of a recently isolated cDNA clone, designated rnat, to genetically polymorphic arylamine N-acetyltransferase (NAT; acetyl-CoA:arylamine N acetyltransferase, EC 2.3.1.5) of rabbit liver was established by its expression in monkey kidney COS-1 cells: (i) cytosols from transfected cultures contained high levels of an Ac-CoA-dependent NAT activity, which was kinetically indistinguishable from that observed in cytosols from livers of genetically rapid acetylator rabbits; (ii) transfected cells also contained an immunoreactive protein, recognized by NAT-specific antibodies, with identical electrophoretic mobility to NAT from rabbit liver. The rnat clone and anti-NAT antibodies were then used to study the relationship between NAT activity, liver enzyme protein, and the level of mRNA in livers from in vivo phenotyped rapid- and slow acetylator rabbits. Livers from slow acetylators were devoid of both immunodetectable NAT protein and its corresponding mRNA. Analysis of genomic DNA with a panel of restriction enzymes revealed the loss of specific hybridizing bands in the DNA of slow-acetylator rabbits. These data strongly suggest that defective arylamine N-acetylation in the rabbit model is caused by a gene deletion resulting in an absence of specific mRNA and NAT enzyme protein. PMID- 2594785 TI - Ca2+/calmodulin sensitivity may be common to all forms of neural adenylate cyclase. AB - The Ca2+/calmodulin (CaM)-activated adenylate cyclase has been implicated as playing an important associative role in classical conditioning in both Aplysia and Drosophila. Studies of the cyclase in mammalian cerebral cortex have suggested that Ca2+/CaM sensitivity is confined to a subpopulation of total cyclase activity. We investigated the properties of cyclase from Aplysia, rat, and bovine central nervous system membranes by using CaM-Sepharose chromatography. Although only a minority of total cyclase activity bound to the CaM column, both bound and unbound fractions of cyclase from all three species showed comparable stimulation by Ca2+ in the presence of CaM. When solubilized bovine membranes were first depleted of most of their endogenous CaM by prior chromatography, binding to the CaM column was substantially increased and Ca2+ stimulation of the unbound fraction was somewhat reduced. However, this reduction in Ca2+ sensitivity resulted from the loss of Ca2+ sensitivity during prior chromatography, rather than from the more efficient separation of Ca2+-sensitive and -insensitive forms. This finding, together with the fact that we never observed any enrichment for Ca2+ sensitivity in the bound fraction over the level in the starting preparation, suggests that the vast majority of the cyclase present in solubilized central nervous system membranes is Ca2+/CaM-sensitive. PMID- 2594786 TI - N-terminal galanin-(1-16) fragment is an agonist at the hippocampal galanin receptor. AB - The galanin N-terminal fragment [galanin-(1-16)] has been prepared by solid-phase synthesis and by enzymic cleavage of galanin by endoproteinase Asp-N. This peptide fragment displaced 125I-labeled galanin in receptor autoradiography experiments on rat forebrain and spinal cord and in equilibrium binding experiments from high-affinity binding sites in the ventral hippocampus with an IC50 of approximately 3 nM. In tissue slices of the same brain area, galanin-(1 16), similarly to galanin, inhibited the muscarinic agonist-stimulated breakdown of inositol phospholipids. Upon intracerebroventricular administration, galanin (1-16) (10 micrograms/15 microliters) also inhibited the scopolamine (0.3 mg/kg, s.c.)-evoked release of acetylcholine, as studied in vivo by microdialysis. Substitution of [L-Trp2] for [D-Trp2] resulted in a 500-fold loss in affinity as compared with galanin-(1-16). It is concluded that, in the ventral hippocampus, the N-terminal galanin fragment [galanin-(1-16)] is recognized by the galanin receptors controlling acetylcholine release and muscarinic agonist-stimulated inositol phospholipid breakdown as a high-affinity agonist and that amino acid residue [Trp2] plays an important role in the receptor-ligand interactions. PMID- 2594787 TI - Silicon modeling of pitch perception. AB - We have designed and tested an integrated circuit that models human pitch perception. The chip receives as input a time-varying voltage corresponding to sound pressure at the ear and produces as output a map of perceived pitch. The chip is a physiological model; subcircuits on the chip correspond to known and proposed structures in the auditory system. Chip output approximates human performance in response to a variety of classical pitch-perception stimuli. The 125,000-transistor chip computes all outputs in real time by using analog continuous-time processing. PMID- 2594789 TI - Characterization of a genetically reconstituted high-affinity system for serotonin transport. AB - By transfecting mouse fibroblast L-M cells with human genomic DNA, we have established and identified several clonal cell lines that stably express a high affinity serotonin (5-HT)-uptake mechanism absent in untransfected host cells. One such cell line, L-S1, possesses features of 5-[3H]HT uptake similar to those previously characterized in the central nervous system and blood platelets: (i) specificity for 5-HT; (ii) antagonism by imipramine, a known inhibitor of high affinity 5-HT uptake; (iii) both Na+ and temperature dependences; (iv) kinetic saturability; and (v) high affinity for 5-HT (Km = 0.39 +/- 0.10 microM; Vmax = 2.14 +/- 0.55 pmol/min per mg of protein). This cell line can be used to compare the relative efficacies of known blockers of 5-HT uptake and thereby offers a rapid and reliable assay system for testing novel inhibitors of this system. Since L-S1 contains stably integrated human DNA in its genome, we postulate that the observed 5-HT-uptake system resulted from the expression of human gene(s) coding for the 5-HT transporter. Thus, cell lines such as L-S1 may represent novel means for screening and developing therapeutic agents specific for neurotransmitter-uptake systems as well as substrates for the cloning and elucidation of the genes encoding the various neurotransmitter transporters. PMID- 2594788 TI - Retinoid requirements for recovery of sensitivity after visual-pigment bleaching in isolated photoreceptors. AB - After visual-pigment bleaching, single isolated rod photoreceptors of Ambystoma tigrinum recover their sensitivity to light when supplied with 11-cis-retinal from liposomes or with 11-cis-retinal bound to interphotoreceptor retinoid binding protein. Bleached rods do not recover sensitivity, or do so only very slowly, after exposure to 11-cis-retinol. The latter retinoid is "toxic" in that rods actually lose sensitivity in its presence. In contrast, bleached isolated cone cells recover sensitivity when either retinoid is supplied. It is suggested that the major pathway for rhodopsin regeneration during dark adaptation in the intact eye is transport of 11-cis-retinal from the pigment epithelium to the retina. The results also suggest that there may be separate pathways for visual pigment regeneration in rods and cones during dark adaptation. PMID- 2594791 TI - Texture interactions determine perceived contrast. AB - For a patch of random visual texture embedded in a surrounding background of similar texture, we demonstrate that the perceived contrast of the texture patch depends substantially on the contrast of the background. When the texture patch is surrounded by high-contrast texture, the bright points of the texture patch appear dimmer, and simultaneously, its dark points appear less dark than when it is surrounded by a uniform background. The induced reduction of apparent contrast is greatly diminished when (i) the texture patch and background are filtered into nonoverlapping spatial frequency bands or (ii) the texture patch and background are presented to different eyes. Our results are unanticipated by all current theories of lightness perception and point to a perceptual mechanism for contrast gain control occurring at an early cortical or precortical neural locus. PMID- 2594792 TI - Project 2000. A new role for staff nurses: the effects of supernumerary students. PMID- 2594790 TI - Ordered appearance of antigenic variants of African trypanosomes explained in a mathematical model based on a stochastic switch process and immune-selection against putative switch intermediates. AB - Antigenic variation of African trypanosomes results from the periodic activation of a single new variant cell surface glycoprotein (VSG) gene out of a repertoire of about a 1000 VSG genes. In spite of the apparently random genetic basis of the process of antigenic variation, the relapsing parasitemias are characterized by an as yet unexplained order of appearance of major VSG variants. Here we mathematically test hypotheses concerning the blood-based parasitemia. In our model the antigenic switches occur at random at the DNA level. A variable proportion of the switches has a short intermediate phase in which two different VSGs simultaneously occur on the cell surface. We show that, in a theoretical population of 230 single expressor variants in an immunocompetent or in an immunodeficient host, it is not possible to explain the ordered appearance of variants by affecting the growth coefficients of single expressors or double expressors or by affecting the antigen switch probabilities. Rather, a realistic parasitemia can be obtained if the majority of switches has a double expressor switch-intermediate phase and if the double expressors have a differential susceptibility to the immune control. This study is significant in providing a theoretical basis for the ordered appearance of variants and in explaining previously unresolved discrepancies between the rate of appearance of new variants in culture and in vivo. In addition, testable predictions as to the development of the infections, switch rate of variants, fraction of double expressors, and parasite mortality coefficients are generated. PMID- 2594793 TI - Too young for the change? Menopause in women under 40. AB - Premature menopause can be devastating for the younger woman with its early infertility and long-term threat of osteoporosis. Oestrogen therapy can help counteract these effects. PMID- 2594794 TI - What is premature menopause? PMID- 2594795 TI - A problem admission who needed understanding. PMID- 2594796 TI - A boost for nursing's stature. PMID- 2594797 TI - Open tube drainage of empyema thoracis. PMID- 2594798 TI - Exploring nurses' attitudes to AIDS. AB - If nurses are to care for people with AIDS properly and inform the public effectively, it is important for them to explore their feelings about the disease and resolve any prejudices they may have. PMID- 2594799 TI - Blood transfusion debate. PMID- 2594800 TI - Pressure sores: removing the causes of the wound. PMID- 2594801 TI - Activation mechanisms of the Xenopus beta globin gene. AB - Comparative protein binding studies have been performed on the Xenopus beta globin gene promoter. Erythroblast nuclear extracts 'footprint' over the erythroid-specific consensus sequence, AGGATAAG, which is located immediately upstream of the CCAAT footprint. Nonerythroid cell extracts do not give rise to an AGGATAAG footprint but rather to an extended CCAAT footprint reminiscent of the CCAAT displacement protein (CDP). Erythroblast extracts also protect a sequence similar to the chicken stage selector element (SSE) immediately downstream of the CCAAT box footprint. In contrast to these discrete footprints observed using erythroblast extracts, Xenopus erythrocyte nuclear extracts give rise to more extensive promoter protection. We have previously reported that this promoter is active in transfected HeLa cells when linked to the SV40 enhancer and that transcriptional activation is accompanied by the formation in the chromatin of a nuclease hypersensitive site (HS) in this region. As a first step towards defining the roles of the various promoter-binding proteins in transcriptional activation and HS formation, we transfected deletion mutants of the promoter into HeLa cells. Deletion of the sequences upstream of -116 had no effect on transcription or HS formation. Indeed the upstream boundary of the HS remained unchanged (at around-170) even though plasmid sequences had replaced Xenopus sequences. If the HS boundary reflects resumption of nucleosomal structure, then sequences downstream of -116 must be able to position a nucleosome from at least 50 bp away. beta globin gene activation in a number of transfected cell lines is absolutely dependent on DNA replication. The replication requirement is not a consequence of template copy number or methylation, nor is it dependent on the direction in which the replication fork passes through the gene. We conclude that replication facilitates active transcription complex formation by disrupting a stable association of the template with negative factors, which could include histones. About 200 bp upstream of the Xenopus beta globin gene promoter is a tract of alternating A and T residues which adopts cruciform geometry at low levels of supercoiling. Because of this sensitivity to torsional stress, we have probed the structure of the (AT)n sequence in microinjected Xenopus oocytes, where the Xenopus beta globin gene is transcribed very efficiently. We find that S1 nuclease cleaves specifically in the middle of the (AT)n tract, suggesting that the gene is under torsional stress. PMID- 2594803 TI - Transcriptional regulation of human gamma globin gene expression. PMID- 2594802 TI - Genetic and biochemical analysis of the mouse beta-major globin promoter. PMID- 2594805 TI - Binding of an erythroid-specific factor to enhancer regions of human globin genes. PMID- 2594804 TI - cis and trans-acting factors regulating gamma and beta globin gene expression in K562 cells. PMID- 2594806 TI - Proteins binding to regulatory elements 5' to the human beta-globin gene. PMID- 2594807 TI - Analysis of human gamma and beta globin gene regulation using transgenic mice. PMID- 2594809 TI - Negative regulation of the human embryonic globin genes zeta and epsilon. PMID- 2594808 TI - Nuclear proteins of a human erythroleukemic cell line that bind to the promoter region of normal and nondeletion HPFH gamma-globin genes. PMID- 2594810 TI - Negative control of the human epsilon-globin gene. PMID- 2594811 TI - A factor from erythroleukemia-like K562 cell nuclei binds intron A of embryonic and fetal globin genes. PMID- 2594812 TI - Cloning of cDNA from induced K562 cells which can activate globin gene expression. AB - A cDNA library from induced K562 cells was constructed and differentially screened for the isolation of clones encoding trans-acting factors which increase globin gene expression. The current study assumes that induced K562 cells contain transcriptionally active factors specific for globin genes which are absent or present only at very low levels in uninduced K562 cells. Upon screening the recombinant library, 75 cDNA clones hybridized specifically with cDNA probes from induced K562 cells and hybridized only slightly or not at all with cDNA probes from uninduced K562 cells and HL-60 cells, or from globin genes. Forty-five of the cDNA clones were full length complements to the corresponding RNA. To screen for trans-acting factors which can activate globin gene expression, the cDNA clones were inserted into a eukaryotic expression vector and co-transfected into HeLa cells with another vector containing the epsilon globin promoter 5' to the bacterial CAT (chloramphenicol acetyl transferase) reporter gene. Partial screening of the 45 full length clones revealed one cDNA (clone #17) that was able to increase CAT activity (driven by the epsilon-globin promoter) by about 2.5 times. This cDNA is 522 nucleotides in length and contains a long open reading frame. Examination with known DNA sequences indicates greater than 95% homology with the ferritin heavy chain. PMID- 2594813 TI - The globin switch at the level of mRNA in the developing mouse. AB - We have carried out a detailed analysis of the relative amounts of zeta, alpha, beta H1, epsilon y2 and adult beta globin mRNA in different tissues of the mouse embryo from Day 8.5 to Day 17.5 i.e. from the first signs of erythropoiesis until almost the end of gestation (birth is Day 19). Interestingly, we find that the zeta to alpha "switch" occurs 24 hours earlier in yolk sac than it does in fetal liver and that the ratio of zeta to alpha mRNA remains higher in the peripheral blood than in the yolk sac or the fetal liver during the latter half of gestation. In fact, zeta mRNA remains present in peripheral blood until Day 15.5. The switch at the mRNA level appears to mimic that found by others [Popp et al, 1987] at the protein level, at least for peripheral blood. This suggests that regulation is not occurring to any major extent at the translational level. The reiteration of the switch in fetal liver suggests that local environmental factors are involved. We find two switches within the beta cluster; beta H1 is expressed first, then epsilon y2 and lastly the two adult beta globins (beta major and beta minor). The switch from beta H1 to epsilon y2 occurs around Day 11.5 and the switch from epsilon y2 to the adult beta globins occurs around Day 15.5. This means that the pattern of expression of the beta-like globin genes in the mouse is more analogous to that found in the human than was previously thought. PMID- 2594814 TI - Transcriptional regulatory factors may control the relative expression of human alpha 1 and alpha 2-globin genes in erythroleukemia cells. PMID- 2594815 TI - Purification of four erythroid cell proteins that bind the promoters of the murine globin genes. PMID- 2594816 TI - Regulated expression of the erythroid-specific-promoter of the human PBG-D gene during erythroid differentiation. PMID- 2594817 TI - DNase I super-hypersensitive sites direct high level erythroid expression of human alpha-, beta- and beta s- globin genes in transgenic mice. PMID- 2594818 TI - Characterization of a human globin enhancer element. PMID- 2594819 TI - Regulatory protein action in the neighborhood of chicken globin genes during development. PMID- 2594820 TI - Three-years' experience of transdermal scopolamine: long-term effectiveness and side-effects. AB - A study was carried out in 68 otherwise healthy male naval crew members to assess the long-term effectiveness and side-effects of routine transdermal scopolamine administration for the prevention of seasickness. The transdermal patches were applied to the mastoid process before each sailing and the subjects generally used 2 patches a week. Check-ups were made every 3 months over a period of 3 years. The average reported seasickness severity (on a scale of 0 to 7) after 6 months at sea prior to the administration of transdermal scopolamine was 5.64 +/- 0.11 (mean +/- S.E.M.), in comparison with 3.14 +/- 0.23 post-administration (p less than 0.001). A significant improvement was found in the self-estimated performance at sea whilst receiving the drug: 65.7% +/- 3.38% (mean +/- S.E.M.), compared to 25% +/- 2.24% beforehand (p less than 0.001). Contact dermatitis precluded the use of transdermal scopolamine in 3 (4.4%) subjects. The only other significant side-effect was dryness of mucous membranes. In conclusion, transdermal scopolamine was found to be effective in the prevention of seasickness and improvement of performance at sea during 3 years of follow-up and routine administration of the drug was not complicated either by severe side effects or by performance disturbances. PMID- 2594821 TI - [Oral and parenteral amoxicillin in the treatment of pneumonia and acute bronchitis]. AB - Oral and/or parenteral amoxycillin was used to treat 52 young and adult patients suffering from moderately severe to severe bronchitis, bronchopneumonia or acute lobar pneumonia. The mean time between onset of disease and start of treatment was 3.8 days. Patients received doses of amoxycillin ranging from 375 mg to 1 g 2 to 3-times daily depending on the severity of the condition for a mean of 6.4 days. There was complete resolution of clinical symptoms such as fever, cough and pleural pain after 3 days in all but 3 of the patients. Response was considered excellent or good in 77% of patients and satisfactory in 14%. Mild to moderate side-effects such as urticaria and nausea were reported in 8 patients but were not severe enough to interrupt treatment. Overall, amoxycillin was considered to be effective in 82% and partially so in 11% of the patients treated. PMID- 2594822 TI - Dose-effect relationship of terbutaline using a multi-dose powder inhalation system ('Turbuhaler') and salbutamol administered by powder inhalation ('Rotahaler') in asthmatics. AB - A study was carried out in 8 patients with chronic stable bronchial asthma to compare the bronchodilator response with terbutaline, administered by a recently developed powder inhalation system ('Turbuhaler') and equipotent doses of salbutamol administered by a widely used powder inhaler ('Rotahaler'). Dose effect relationships with usually applied clinical doses of the bronchodilators were estimated by maximal expiratory flow-volume analysis and airway resistance estimates from body plethysmography. There was no significant difference in clinical response using either inhaler. The equal and opposite changes in forced vital capacity and residual volume with increasing dose indicate an improvement in peripheral airway resistance and, therefore, adequate peripheral powder deposition of the bronchodilators. Only at the highest dose was a mild increase noted in pulse frequency and tremor score with both systems. It is suggested that, because of the multi-dose character, absence of additives, easy handling (no capsule loading) and low inspiratory flow needed for actuation, the 'Turbuhaler' system may be considered preferable for the application of a bronchodilator in children and severely obstructed adults. PMID- 2594823 TI - [The synthesis of P-substituted DL-2-phenylglycine octylesters]. AB - 9 Titel compounds (p-RC6H4)CH(NH2.HCl)COO (CH2)7CH3 [R = F, Cl, HO, CH3O, CH3(CH2)3O, C6H5CH2O, CH3, (CH3)2CH and (CH3)2N.HCl] were obtained by esterification of p-substituted DL-2-phenylglycines with octanol either in the presence of dry hydrogen chloride (procedure A) or with thionyl chloride (procedure B). The advantages of the procedure B are the mild conditions, the more pure products, the possibility of esterification of diamino acids, and the stability of alkoxy groups as substituents. The synthesized octylesters are potential antiinflammatory and analgesic substances with spasmolytic activity. PMID- 2594824 TI - [Synthesis and antitumor action of N,N-di(2-chlorethyl)-hydrazines of alpha aminocarboxylic acid antimetabolites]. AB - The N,N-di(2-chlorethyl)hydrazides of the following alpha-aminocarboxylic acid antimetabolites: methioninsulphoxide, ethionine, 2-, 3- and 4 fluorophenylalanine, 4-nitrophenylalanine and 2,2-dimethyl-thiazolidine-4 carboxylic acid were synthesized. Preliminary studies of the activity on experimental tumour models were carried out. It was shown that these compounds have a high antitumour effect (80-100%) on sarcoma Yoshida and carcinosarcoma Walker. PMID- 2594825 TI - [Preparation of preoral sustained-release preparations with a base of biodegradable polymers. 3. Preparation of matrix tablets with a base of poly-3 hydroxybutyric acid]. AB - Poly-3-hydroxybutyric acid belongs to the biological polymers, which are produced by bacterials. The determination of the grain size, moisture content, flowability and the parameters for the direct compression was performed in regard of their use as auxillary substance for the preparation of solid sustained release dosage forms. The production of the matrix tablets was performed on the basis of a factorial design. The content of substance, an addition of Heweten 12 and the compression power served as factors. Caffeine was used as model drug. The in vitro release values show, that all three factors have an influence of the drug release. Optimized matrix tablets were produced on the basis of this result. PMID- 2594826 TI - Preparation of a prolonged-release tablet formulation of diclofenac sodium. Part 1: Using chitosan. AB - Chitosan was used to prepare a prolonged-release tablet formulation of diclofenac sodium. Tablets were made by both direct-compression and wet granulation methods. The physical properties of tablets and granules were tested. The dissolution tests were performed by using USP dissolution and flow-through cell methods. A microcomputer program was used for the kinetic assessment of dissolution data. It was found that chitosan may be used for the preparation of the prolonged-release tablet of diclofenac sodium. PMID- 2594827 TI - [Biotransformation of phenolglycosides leiocarposide and salicin]. AB - Leiocarposide (1; 3-beta-D-glucopyranosyloxy-2-methoxy-6-hydroxy-benzoic acid -2' beta-D-glucopyranosyloxybenzyl ester) is a phenolic glycoside from Solidago virgaurea L. After oral administration to rats it will be only poorly absorbed and mostly unchanged fecaly excreted. In the urine were found less than 10% as metabolites: leiocarpic acid (3; 3,6-dihydroxy-2-methoxy-benzoic acid, 2% of the administered dose), 3-conjugates (2%), salicylic acid (5; 0.5%), 5-conjugates (0.1%) and salicyluric acid (6; 0.5%). On the other hand salicin (2), structural part of 1, is good absorbed. In the urine were excreted 15% of the unchanged drug and the following metabolites: 0.1% saligenin (4), 30% 5, 5% 5-conjugates, 0.1% 6, 2% gentisic acid (7) and 0.1% 2,3-dihydroxy-benzoic acid (8). The different metabolic rates are explicable by the high stability of the ester bond of 1. It is hydrolyzed in artificial intestinal fluid only very slowly (t1/2 = 41.7 h). PMID- 2594828 TI - Birch sap and birch leaves extract: screening for antimicrobial, phagocytosis influencing, antiphlogistic and antipyretic activity. AB - Birch sap and birch leaves extract have been screened for antimicrobial, phagocytosis-influencing, anti-inflammatory and antipyretic activity. No antimicrobial effects could be detected in the agar-diffusion test with staphylococcus as test strain, whereas birch sap exhibited some inhibitory effect on phagocytosis, which exceeded that of the citric acid added to the birch sap as preservative. In rats, only the high doses of 1 and 2 ml/100 g b.m. birch sap had a weak and short-lasting anti-inflammatory activity against the Carrageenin edema, whereas birch leaves extract proved to be ineffective. Fever induced by baker's yeast in rats was inhibited by birch leaves extract in the high dose of 4 ml/100 g b.m. significantly, but not by birch sap, and only for a short period. Acetylsalicyclic acid had a much higher anti-inflammatory and antipyretic activity. Altogether despite of detectable anti-inflammatory, antipyretic and phagocytosis-inhibiting effects of these birch products no therapeutic activity of importance compared with classical and modern antipyretics-analgetics can be demonstrated. PMID- 2594829 TI - Effect of some 4-alkyl-5-dimethylamino-1-phenyl-1-penten-3-one hydrochlorides and related compounds on respiration in mouse liver mitochondria. AB - 5-Dimethylamino-1-phenyl-1-penten-3-one hydrochloride (1a) has high inhibiting properties in mitochondria isolated from mice liver. Substitution at the 4 methylene group of 1a by different alkyl substituents lead to compounds with wide variation in respiration-inhibiting properties. No correlations were found between either the Charton steric parameter (v), Taft inductive value (f*) or fragmental constant (f) of the substituents at position 4 of the Mannich bases with inhibition of respiration. However the biological results suggested two receptor sites were present in the mitochondria which may interact with the Mannich bases namely a common receptor for all compounds and in addition a narrow hydrophobic binding area which can accommodate a n-butyl or higher alkyl groups which are present in some of the compounds. PMID- 2594830 TI - [Improvement of the solubility behavior of problem drugs. 20. The effect of pharmaceutical excipients on the wetability of iomeglamic acid]. PMID- 2594831 TI - Biodegradation of surface active amine oxide and quaternary ammonium salt germicides. PMID- 2594832 TI - [Bacteriostatic action of 1-(n-alkoxymethyl)-3-ethylpyridinium chlorides]. PMID- 2594833 TI - [The antiviral action of ergosterol peroxide]. PMID- 2594834 TI - Care and caring: the concepts explored. PMID- 2594836 TI - Continuing Professional Education Accreditation Program (CPEAP): a Philippine experience. PMID- 2594835 TI - What does "wholistic" care mean? PMID- 2594837 TI - The biological effects of increased ultraviolet radiation: an update. PMID- 2594840 TI - [Plaster casts in orthopedics]. PMID- 2594838 TI - Resolution of two emission spectra for tryptophan using frequency-domain phase modulation spectra. AB - We describe a novel application of frequency-domain fluorometry which allows resolution of the decay times and emission spectra of samples which display multi exponential decay kinetics. This method does not require any previous knowledge about the decay times or any assumptions about the shape of the emission spectra. We record the wavelength-dependent phase angles and modulations (phase angle and modulation spectra) using a number of light modulation frequencies. The data is analyzed by non-linear least-squares to recover the emission spectra and their associated decay times. Phase and modulation spectra (PM Spec) were used to recover the emission spectra associated with the two decay times of tryptophan at pH = 7 (0.54 and 3.44 ns). The emission spectra of these components are centered at 340 and 355 nm, respectively, with the amplitude of the 0.54 ns component contributing 6% to the total emission. These results are in agreement with previous time-resolved studies by Szabo and Rayner [J. Am. Chem. Soc. 102, 554 563 (1980)]. Control experiments were performed on mixtures of N-acetyl-L tryptophanamide (NATA) and PPD, which demonstrate our ability to recover the spectra and decay times from two component mixtures. NATA itself displayed a single decay time and only one emission spectrum. PMID- 2594839 TI - Effects of ultraviolet light on thymidine incorporation and DNA chain elongation in photoreactivable insect cells. AB - An insect cell line, IAL-PID2, was exposed to UV and analyzed for its ability to incorporate [3H]-thymidine and to elongate replicon-sized DNA fragments. After exposure to 5 or 10 J/m2 UV, the cells exhibited a rapid and prolonged depression in the rate of thymidine incorporation. Photoreactivation reduced this depression but did not entirely reverse it. For exposures of 5 J/m2 or above, full recovery did not occur until 18 h after exposure. The blockage of fork progression after UV exposure was fluence-dependent, with replication segments after exposure to 20 J/m2 being shorter than those observed after exposure to 10 J/m2. Immediately after exposure to either 10 or 20 J/m2, photoreactivation reversed blockage of fork progression, indicating that the (5-6) cyclobutyl pyrimidine dimer is responsible for blockage. This also indicates that blockage of fork progression may not be the only factor responsible for the prolonged depression seen in thymidine incorporation. Three hours after exposure to either 10 or 20 J/m2, replication segments were still significantly shorter than control segments. Photoreactivation completely reversed blockage after exposure to 10 J/m2, but did not completely reverse blockage after exposure to 20 J/m2, indicating that at such fluences, other lesions may play a role in UV-induced blockage of fork progression. PMID- 2594841 TI - [Nursing personnel in hospital care]. PMID- 2594842 TI - [The education of nurses in China]. PMID- 2594843 TI - [The visiting cards of the Danish nursing education system]. PMID- 2594844 TI - [Arterial hypertension]. PMID- 2594846 TI - [Community health nursing in the basic health care system]. PMID- 2594845 TI - [Life is movement]. PMID- 2594847 TI - [The demand for the work of a community health nurse in a district]. PMID- 2594848 TI - [Student opinions about work in the community]. PMID- 2594849 TI - [Student opinions about work in the community]. PMID- 2594850 TI - [Care of the patient undergoing orthopedic treatment]. PMID- 2594851 TI - [Orthopedic rehabilitation]. PMID- 2594853 TI - [The effects of improving the process of communicating]. PMID- 2594852 TI - [Aging--old age]. PMID- 2594854 TI - [They bet on orthopedics]. PMID- 2594855 TI - [A school for young parents]. PMID- 2594856 TI - [Books help in treatment]. PMID- 2594857 TI - [The concept of education in the Nursing Section of the Medical Academy in Krakow]. PMID- 2594858 TI - [The measurement of arterial blood pressure]. PMID- 2594859 TI - [Not just a scalpel]. PMID- 2594860 TI - [Osteoarticular tuberculosis is as threatening as in the past]. PMID- 2594861 TI - [The quality of life of nurses]. PMID- 2594862 TI - [A new look]. PMID- 2594863 TI - [Care of the patient undergoing orthopedic treatment. II]. PMID- 2594864 TI - Suppression of humoral immune responses in mice by antigens derived from Trichomonas vaginalis. AB - The occurrence of immunosuppression in mice inoculated with antigens prepared from Trichomonas vaginalis was investigated in this study. One hundred and fourteen BALB/c mice with half of each sex were divided into 19 groups and inoculated with different antigen preparations before or after sheep red blood cell (Srbc) immunization. Antigen preparations included live T. vaginalis (LTV), excretory and secretory products (ESP), and freeze and thaw antigens (FTA). The immunosuppressive effects of these T. vaginalis-derived antigens were demonstrated by the decrease of hemagglutination titers to Srbc. Results indicated that all three antigen preparations exhibited immunodepressive potentials in the primary and secondary responses to Srbc. Among them, FTA showed the highest inhibitory effect. The duration of the effect persisted for 21 days. The immunosuppressive effect was not observed for antigens which were given after Srbc injection. PMID- 2594865 TI - Distribution of serotonin immunoreactive neurons in the brainstem of the hamster, guinea pig, rabbit, and rat. AB - Immunohistochemical techniques were employed to study the distribution of serotonin (5-HT) immunoreactive neurons in the brainstem of the hamster, guinea pig, rabbit and rat. 5-HT neurons were principally found to be concentrated in the midline raphe nuclei, particularly, the raphe pallidus, raphe obscurus, raphe magnus, raphe median, raphe pontis and raphe dorsalis nuclei. Characteristically, these cell bodies are displayed in bands or wing-like patterns which extend laterally from the raphe into reticular formations. The formations often appear to blend with the catecholamine system. They are particularly evident in the brainstems of the rabbit and hamster which contain wider and more lateral extensions of the serotonergic (5-HT) neurons than those observed in the brainstems of the rat and guinea pig. The widespread distribution of 5-HT immunoreacted cell bodies in the brainstem shows that there are significant prospects of 5-HT in neuronal activities. PMID- 2594866 TI - Morphological and morphometric studies of early myelination in the cervical dorsal funiculus of the newborn mouse spinal cord. AB - The early myelination of the dorsal funiculus at the level of the 4th cervical spinal cord was ultrastructurally studied in the one-day-old mouse. It was found that the fibers were mainly unmyelinated. However, some early myelinated fibers were scattered among unmyelinated fibers. In the initial stage of the myelination, the axon was partially contracted by a piece of cytoplasmic process of the oligodendroglial cell. The two lips of the oligodendroglial process then extended and converged, enwrapping the axon completely and forming the first contact point. With the anchorage of that contact point, the two lips of the process became elongated and enfolded by each other, and produced the internal and external tongues of the future myelin sheath. More contact points were formed at a regular interval by the regional fusion of the two external surface layers of the opposed cytoplasmic membranes of adjacent tongue processes. With the advanced bidirectional spiralization of the two tongue processes, many contact points were found between the adjacent lamellae of the concentrically arranged oligodendroglial process; simultaneously, the cleft between the neighboring contact points disappeared and formed the initial sites of the intraperiod line. During the early myelination, one single axon ensheathed concentrically by two different oligodendroglial processes as well as several axons enwrapped by a continuous spiral myelin sheath of one oligodendroglial cell were frequently observed. The cross-sectional areas of unmyelinated axons varied from 0.01 to 0.2 micron 2, with a median of 0.07 micron 2; whereas, that of promyelinated axons ranged from 0.09 to 1.4 micron 2, with a median at 0.61 micron 2. These data support the suggestion that the axon calibre is a critical factor for the initiation of central myelination. PMID- 2594867 TI - Plasma MHPG and age at onset in depressed patients. PMID- 2594869 TI - The development of social group formation in normal and mentally retarded persons from early childhood through old age: neuropsychiatric, developmental, and cognitive implications. AB - To test the hypothesis that mentally retarded persons exhibit identifiable styles of social grouping, the size and sex composition of spontaneous social groups were studied in 570 mentally retarded and 3,030 nonretarded persons from preschool-elderly ages. Both populations showed similar developmental trends: group sizes increased through childhood, decreased thereafter until middle age, and increased again in the elderly. However, mentally retarded persons formed smaller groups at all ages: solitary individuals predominated with few groups larger than dyads. A subgroup of lower-functioning retarded persons formed even smaller groups. Nonretarded females were more aggregative than males, but mentally retarded persons showed no such sex differences. PMID- 2594868 TI - Lack of specificity of reduced platelet imipramine binding in different psychiatric conditions. AB - We compared 3H-imipramine binding in 10 major depressives with that in 29 healthy volunteers, 13 patients with panic disorder, 9 patients with bulimia, 9 suicide attempters, and 6 schizophrenic patients. None of the comparison groups had histories of major mood disorders, except the suicide attempters. We found a significant reduction of the maximum binding capacity (Bmax) in all groups of patients as compared with healthy controls. These data cast doubt upon the specificity of the decrease of platelet 3H-imipramine binding in major depression, but suggest a possible pharmacological common denominator involving the serotonin system. PMID- 2594870 TI - Haloperidol and reduced haloperidol plasma levels in Chinese vs. non-Chinese psychiatric patients. AB - Haloperidol and reduced haloperidol plasma concentrations were measured in age matched Chinese and non-Chinese patients (n = 32). Steady-state plasma concentrations were obtained 10-12 hours after the bedtime dose. Haloperidol and reduced haloperidol concentrations were measured by liquid chromatography and radioimmunoassay. Haloperidol plasma concentrations did not significantly differ between the populations, but reduced haloperidol levels were 3 times greater in non-Chinese patients than in Chinese patients. The incidence of extrapyramidal side effects was higher in Chinese patients (18 vs. 10), while non-Chinese patients with extrapyramidal symptoms had higher reduced haloperidol plasma levels. Logistic regression analysis revealed that ethnicity and reduced haloperidol/haloperidol ratios were important variables in predicting extrapyramidal symptoms. These results suggest that the metabolism and disposition of haloperidol and reduced haloperidol could differ among ethnic populations. PMID- 2594872 TI - Platelet serotonin uptake in panic disorder patients: a replication study. AB - Platelet serotonin uptake was measured in 29 patients with DSM-III panic disorder or agoraphobia with panic attacks and compared to values obtained in 23 controls. Both the affinity constant (Km) and the maximal rate of uptake (Vmax) were determined in a buffered medium using 14C-serotonin. Patients and controls did not differ significantly with respect to age or Km values. A statistically significant difference was observed for Vmax (mean +/- SD = 65 +/- 22 pmol/10(8) platelet/min in patients vs. 44 +/- 13 pmol/10(8) platelets/min in controls). This finding suggests an overactivity of peripheral serotonergic function in panic disorder, which may also imply a similar dysfunction centrally. PMID- 2594871 TI - The relationship of panic disorder and its treatment outcome to 24-hour urinary MHPG levels. AB - Levels of 24-hour urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) were not markedly elevated in a group of 35 panic disorder patients when compared to healthy controls (mean = 2,430 micrograms/day vs. 2,130 micrograms/day). There was a weak association between elevated pretreatment levels of MHPG and a positive treatment response to alprazolam or diazepam. Alprazolam and diazepam may differ in their effects on MHPG. PMID- 2594873 TI - Dexamethasone suppression test in positive and negative schizophrenia. AB - Fifty-four inpatients with a DSM-III diagnosis of schizophrenia were studied. Patients were divided into positive and negative subtypes of schizophrenia according to Andreasen's criteria. Blood samples were obtained from all patients for 2 consecutive days to determine plasma cortisol concentrations before and after a single administration (1 mg, p.o.) of dexamethasone at 11 p.m. The results revealed a significant increase in plasma cortisol levels in schizophrenic patients, with 40% of the patients being nonsuppressors on the dexamethasone suppression test. A higher percentage (62.5%) of patients with the negative form of schizophrenia were nonsuppressors. PMID- 2594874 TI - Behavioral performance and seizure activity of lithium-intoxicated Sprague-Dawley rats treated with theophylline. AB - Male Sprague-Dawley rats were divided into four groups that were treated with various combinations of lithium, saline, and theophylline, i.e., saline/saline, saline/theophylline, lithium/theophylline, and lithium/saline. Neurobehavioral testing of cerebellar and neuromuscular functioning, and determination of the effect of the drug combinations on the animals' seizure threshold concluded that while theophylline increases lithium clearance, it does not exacerbate lithium neurotoxicity. PMID- 2594876 TI - Psychiatric morbidity, platelet monoamine oxidase and tribulin output in headache. AB - A significantly higher proportion of patients with headache showed scores in the psychopathological range of the General Health Questionnaire (GHQ) compared with controls, with ratings particularly high on the anxiety and depression subscales. Across the whole group, there was a significant negative correlation between platelet monoamine oxidase (MAO) activity and GHQ score overall, and with the anxiety and depression subscales. There was a significant positive correlation between platelet MAO activity and urinary output of the endogenous MAO inhibitor, tribulin. Within the migraine group, there was a significant negative correlation between tribulin output and GHQ score. These findings suggest that the biochemical nature of the anxiety associated with migraine may differ from that in other conditions such as generalized anxiety disorder where high platelet MAO activity and high tribulin output have been reported. PMID- 2594875 TI - Diagnostic determinants of response to treatment with tricyclic antidepressants: a polydiagnostic approach. AB - In an attempt to find diagnostic predictors of treatment response, 45 inpatients with major depression in a randomized trial received amitriptyline or imipramine for 23 days after a washout period of 16 days. A polydiagnostic approach was applied to the classification of endogenous depression. Only a minority of diagnostic schedules for endogenous depression proved predictive of a more favorable course during antidepressant treatment: the criteria of D. F. Klein, the Newcastle Scale II, and the Vienna Research Criteria. The symptoms of nonreactivity of mood and diurnal variation were the only endogenous symptoms with predictive ability. In addition, psychotic features and secondary depression predicted an unfavorable course, whereas characteristics of previous course (bipolarity, recurrence) were not predictive. PMID- 2594877 TI - Concurrent validity of GHQ-28 and PSE as measures of change. AB - Substantial cross-sectional correlations have been reported between the GHQ and PSE (and CIS) total scores. Although necessary, this is not a sufficient condition for assuming good validity of the GHQ as a severity measure in longitudinal and health care evaluation studies. For this purpose the GHQ should also accurately reflect changes in severity over time. To examine their concurrent validity, GHQ and PSE scores were compared, in a three-wave longitudinal study, among 175 new psychiatric out-patients. Using a longitudinal structural equation model that takes measurement error into account, the strength of both the cross-sectional and longitudinal relationship between GHQ and PSE were estimated. The GHQ performed remarkably well; changes in severity as defined by PSE-ID and PSE total score were clearly reflected by changes in GHQ scores. The revised scoring method of the GHQ proposed by Goodchild and Duncan-Jones did not yield superior results. PMID- 2594878 TI - The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): socio demographic correlates, reliability, validity and some norms. AB - The IQCODE is a questionnaire which asks an informant about changes in an elderly person's everyday cognitive function. The questionnaire aims to assess cognitive decline independent of pre-morbid ability. In the present study, the IQCODE was administered to a sample of 613 informants from the general population. In addition, the questionnaire was administered to informants of 309 dementing subjects who had filled it out one year previously. A principal components analysis, using the general population sample, confirmed that the IQCODE measures a general factor of cognitive decline. The questionnaire was found to have high internal reliability in the general population sample (alpha = 0.95) and reasonably high test-retest reliability over one year in the dementing sample (r = 0.75). The total IQCODE score, as well as each of the 26-items, was found to discriminate well between the general population and dementing samples. The correlation with education was quite small (r = -0.13), indicating that contamination by premorbid ability is not a problem. PMID- 2594879 TI - The Parental Bonding Instrument (PBI): an epidemiological study in a general population sample. AB - The Parental Bonding Instrument (PBI) was used in a 2-wave community survey of 386 persons. The two factor structure of the instrument was confirmed, as well as the high stability of its scales over time. Respondents who had had children differed significantly from others. No association was found between social desirability, neuroticism or extraversion and either of the scales. No association was observed between the scales and psychiatric disorder, despite using covariance structure analysis to remove the effects of age and attenuation due to measurement error. Estimates of relative risk for affectionless control were low in contrast to estimates calculated from samples with psychiatric disorders. These findings may be characteristic of symptomatic persons in a general population. Because of the importance of the affectionless control construct, the findings invite further investigation in other community and treated samples. PMID- 2594880 TI - Bulimia nervosa: a four- to six-year follow-up study. AB - A consecutive series of 45 female bulimic patients treated by one of us was followed four to six years after termination of treatment. Thirty-five (78%) were successfully followed, six refused to participate in the study and four were untraced. At least seven (16%) had diagnosable bulimia nervosa at follow-up, and at least another seven had a subclinical form of the disorder during the six months prior to follow-up. Relapse into anorexia nervosa was uncommon, and the severity of the bulimic features had improved even among those still diagnosable as having the disorder. Affective disturbances were common among those who were bulimic. The findings were discussed in terms of the intermediate term outcome of the disorder and its identity as a clinical entity. PMID- 2594881 TI - The pattern of function-related regional cerebral blood flow investigated by single photon emission tomography with 99mTc-HMPAO in patients with presenile Alzheimer's disease and Korsakoff's psychosis. AB - Single photon emission tomography (SPET) with the lipophilic blood flow marker 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO) has been used to determine regional uptake of radiolabel into brain regions of patients with presenile Alzheimer's disease and Korsakoff's psychosis, and age-matched controls. Using occipital cortical uptake as reference area, the pattern of relative regional cerebral blood flow (rCBF) was determined in other cortical areas and basal ganglia. In Alzheimer's disease, reduction in rCBF occurred most strikingly in posterior temporal and parietal areas. By contrast, in Korsakoff's psychosis, posterior temporal rCBF was maintained, although there was a trend to reduced tracer uptake in other cortical areas. These impairments of flow were correlated with impairments of neuropsychological function. In Alzheimer's disease, left posterior temporal and left parietal regions in particular showed rCBF to be strongly correlated with most aspects of cognitive function. In Korsakoff's psychosis, however, impaired flow in frontal regions was correlated with impaired performance on tests of memory and orientation. The findings in Alzheimer's disease show quantitative parallels with those from studies using Positron Emission Tomography (PET), and extend our understanding of the relationship between cognition and regional brain function in dementia. The findings in Korsakoff's psychosis offer the first direct evidence linking frontal lobe dysfunction with the cognitive impairment seen in the disorder. PMID- 2594882 TI - The neuroendocrine responses and psychological effects of infusion of L tryptophan in anorexia nervosa. AB - The secretion of prolactin and growth hormone (GH), together with subjective ratings of sedation and hunger, were determined in 13 in-patients with anorexia nervosa and 15 controls during the intravenous infusion of L-tryptophan (100 mg/kg). Prolactin responses were not different between groups but GH responses were markedly blunted in patients. In addition sedation responses in patients were attenuated compared with controls. Hunger ratings were reduced by the infusion in controls but were too variable to be interpreted in the patients. Plasma amino acid levels were also determined before and after infusion of L tryptophan. Tryptophan levels were comparable in the two groups as were the levels of tyrosine, phenyl alanine, valine, leucine and iso-leucine. The results suggest that some aspects of 5-hydroxytryptamine function may be attenuated in anorexia nervosa. However, they undoubtedly contrast with the finding of enhanced hormonal responses in acute dieting and may be relevant to the interpretation of similar experiments in depressive illness. PMID- 2594883 TI - Filling the preparatory interval with temporal information or visual noise: crossover effect in schizophrenics and controls. AB - Three variants of a simple reaction time task with regular and irregular series of different preparatory intervals (PIs) were presented to schizophrenics and a control group of alcoholics and normals: the visual warning signal (WS) either (1) remained fixed, (2) shrank at a constant rate, or (3) changed in size erratically. Time information provided by shrinking WSs reduced the average reaction time in all groups and attenuated the crossover effect (COE) of schizophrenics, although even here more schizophrenics than controls had COE scores greater than or equal to 25 msec. Erratically changing WSs introduced the COE in controls. Within groups the COE was not related to general response speed, age, duration of hospitalization, or medication. Results are interpreted as indicating that schizophrenics eschew controlled anticipatory processes on the basis of WS- and PI-information which are crucial for motor preparation when PIs are too long to allow an automatic perceptual grouping of warning and imperative stimulus. This may also occur in controls when time estimation is impeded by distraction. PMID- 2594884 TI - The role of provocative visual stimuli in agoraphobia. AB - Three studies examine the role that provocative visual stimuli have in eliciting anxiety reactions in people with agoraphobia. Such stimuli elicit more anxiety in agoraphobic patients than control subjects. The effect of visual stimulation appears to be specific: (1) non-visual stimulation is without comparable effect; (2) both control and agoraphobic groups show similar effects of visual stimulation on another reaction such as headache. The anxiety effects of visual stimuli are correlated with the extent to which subjects experience depersonalization and somatic symptoms of agoraphobia, but not correlated with depression or the behavioural or cognitive aspects of agoraphobia. Alternative accounts of the possible role of visual stimulation in the anxiety reactions of agoraphobic patients are discussed. PMID- 2594885 TI - Psychiatric morbidity in multiple sclerosis: a clinical and MRI study. AB - This study reports the psychiatric morbidity in 116 patients with definite multiple sclerosis (MS). The presence of brain pathology was investigated using magnetic resonance imaging (MRI). A group of 48 physically disabled controls suffering from rheumatic or neurological conditions not involving the brain was used for comparison. Normative MRI data were obtained from a group of 40 healthy volunteers. Psychiatric morbidity was significantly higher in the MS group with nearly half of the patients scoring as cases at interview. There was no evidence to suggest that psychiatric symptoms in isolation were the first manifestation of MS in the present material. The presence of psychiatric illness at interview was significantly related to the degree of social stress as perceived by the patient. The severity of MRI abnormalities was greater in those with longer histories and greater physical disability, but did not show a significant relationship with global measures of psychiatric disability. Of the various psychiatric symptoms elation was significantly correlated with the presence of widespread MRI abnormalities, while flattening of affect, delusions and thought disorder correlated with the degree of pathology in the temporo-parietal region. PMID- 2594886 TI - How does gender influence age at first hospitalization for schizophrenia? A transnational case register study. AB - Numerous studies have reported a lower mean age at first hospitalization for schizophrenia in males than in females. For this finding not only a gender difference in age at first onset of schizophrenia, but also other factors can be responsible. With the aim of providing a comprehensive analysis of gender differences in onset, symptomatology and course of schizophrenia, we started by testing the hypothesis postulating a gender difference in mean age at first hospitalization. By using the Danish and the Mannheim psychiatric case registers we analysed all hospital admissions for schizophrenia and related diagnoses and all previous admissions for other diagnoses of the Danish population in 1976 and those of the inhabitants of the German city of Mannheim in the period of 1978-80. Artefacts were controlled for systematically. The impact of intervening variables such as selection factors as well as the influence of gender on the ascription of a diagnosis of schizophrenia for the first time were assessed. We found a mean difference of 5 to 6 years in age at first hospitalization between males and females in both countries when a broad definition of the diagnosis was used and of 4 to 5 years when a restrictive definition was applied. The higher mean age at first hospitalization among females is not attributable to artefacts, diagnostic procedures or to any essential extent to gender differences in help-seeking behaviour or occupational status. When a distinction was made between 'single' and 'married', the significant difference in age at first hospitalization between the sexes disappeared in singles. With case register data and without knowing the chronological order of marriage and onset of the disease, it remains an open question whether this finding can be explained by purely correlative associations between sex, marital status and age of onset or by causal effects. PMID- 2594887 TI - The prevalence of psychiatric disorder among female new referrals to a migraine clinic. AB - In a consecutive series of 46 female new referrals to a migraine clinic, 17 patients (37%) complained of increased irritability and/or depression in association with more than 50% of their migraine attacks. This was not related to the attack frequency or duration. Sixteen patients (33%) met DSM-III criteria for a current diagnosis of an affective syndrome and when present this was significantly associated with these complaints. PMID- 2594888 TI - Characteristic psychiatric symptomatology of post-traumatic stress disorder in veterans: a three year follow-up. AB - This study assessed the clinical picture of two groups of Israeli veterans of the Lebanon war: (a) veterans who sustained a combat stress reaction (CSR) (N = 213), and (b) matched controls not so diagnosed (N = 116). Subjects were screened at three points--one, two, and three years after their participation in the war. The results indicated that Post-Traumatic Stress Disorder (PTSD) was correlated with a wider range of general psychiatric symptomatology, as measured by the SCL-90. Moreover, among PTSD veterans, those who suffered from an antecedent CSR reported wider and more severe symptomatology. This trend was observed at all three time points. The most salient symptoms were obsessive-compulsive tendencies and anxiety, followed by depression and hostility. PMID- 2594889 TI - Biopsychosocial aspects of long-term survival on end-stage renal failure therapy. AB - At ten-years follow-up of 64 haemodialysis patients, 43 had died and 21 were alive, twelve with cadaver renal transplants and nine on haemodialysis. Examination of the influence of psychological, demographic, physical and biochemical factors revealed the Beck Depression Inventory and age as the two most important predictors of survival. The behaviour of the patient was directly responsible for five (11.6%) of the deaths, by suicide in three cases and dietary non-compliance in two cases. Hypothetical mechanisms linking depression with reduced survival have been reviewed. As the impact of depression on survival was maximal in the first few years of dialysis, monitoring for depression should be incorporated into routine care from the start of dialysis together with evaluative interventions that might enhance survival. PMID- 2594890 TI - Eating disorders: lessons from a cross-cultural study. AB - Five hundred and eighty schoolgirls living in a small North Indian industrial town were screened using the EAT-26. Although twenty-nine per cent scored above the threshold for the questionnaire (greater than or equal to 20), closer scrutiny of the pattern of responses revealed misinterpretations of a large number of questions possibly on a conceptual basis. Linguistic and conceptual pitfalls inherent to cross-cultural epidemiological research are discussed with reference to previous work. PMID- 2594891 TI - Mana, tapu, noa: Maori cultural constructs with medical and psycho-social relevance. AB - This paper discusses three concepts, mana, tapu and noa, that lie at the heart of Maori culture. These concepts are inter-related and concern power and influence, with political (or secular) authority implicit in mana and ritual (or religious) authority determined by tapu and noa. The paper explores their importance for the understanding of the ethnic views on aetiology and management of illness, the mechanisms of social organization and control, and the behaviour of individuals. Although the belief in these concepts exists in only an attenuated form in modern Maori society, their importance becomes obvious to any psychiatrist or physician working with Maori patients. PMID- 2594892 TI - Clinical judgement and the standardized interview in psychiatry. AB - There has been little discussion of the advantages and disadvantages of allowing a psychiatrist to make clinical judgements about the presence or absence of symptoms in administering currently used standardized psychiatric interviews. This paper reports an examination of the value of clinical judgements in defining cases of minor psychiatric disorder, by studying existing data in which the Clinical Interview Schedule (CIS) was used. This comparison can be made because the first section of the CIS is largely self-report while interviewers are also instructed to use clinical judgement in the second section to decide on ratings. The results indicate that in the context of identifying minor psychiatric disorder the ratings requiring clinical judgement add little information to those based on self-report, may be less reliable and may lead to the biased assessment of anxiety and depression. PMID- 2594893 TI - Severity of withdrawal symptoms as a predictor of outcome of an attempt to quit smoking. AB - In 227 smokers' clinic clients who managed at least one week of abstinence, ratings of withdrawal symptoms were used to predict subsequent return to smoking. Depression, time spent with urges to smoke, and difficulty not smoking during the first week of abstinence were significantly associated with lapse back to smoking during the second week. Depression and difficulty not smoking during the second week significantly predicted smoking status during the third week. No withdrawal symptoms during the third week were associated with a return to smoking during the fourth week. The predictive power of withdrawal symptoms was over and above that of smoke intake and dependence. The findings provide some support for the view that reduction of withdrawal symptoms may be a worthwhile target in programmes for helping smokers to quit. PMID- 2594894 TI - Classification of depression by grade of membership: a confirmation study. AB - One hundred and thirty out-patients with depression were studied by grade of membership multivariate (GOM) analysis. Five depressive types were generated. Pure Type I represented a mild form of melancholia in older, stable males, who showed a modest drug response. Pure Type II included obsessive-anxious symptoms in older patients who responded well to an MAOI drug, but poorly to placebo. Pure Type III was a mildly symptomatic form of depression which responded well to placebo. Pure Type IV included features of agitation, mood worsening later in the day, anorexia and depersonalization; it was commonly precipitated by external stress and MAOI treatment was more effective than placebo. In Pure Type V depression, patients were mostly younger females with high levels of symptomatology, atypical vegetative symptoms, unstable life-styles, disadvantaged backgrounds and a poor response to MAOI and placebo. These results resemble in many ways our earlier GOM study of depression, as well as other multivariate studies of depression in the literature. PMID- 2594895 TI - The reliability of diagnostic coding in psychiatric case registers. AB - In total, 103 cases were randomly selected from the Groningen, Nottingham and South Verona registers. Six raters (two in each of the register areas) were involved in coding these cases according to the ICD-9. In general, interrater agreement was satisfactory when codes were grouped into a limited number of categories. Nevertheless, considerable variation in agreement rates was found. We distinguished three steps in the diagnostic process. The selected logistic model showed that reliability is significantly affected in each step, but only substantial in the first where clinicians formulate a diagnosis. PMID- 2594896 TI - Neural plasticity in vivo: opioid sensitivity of memory develops gradually after a septal lesion. AB - Neuronal plasticity can manifest itself in alterations in the sensitivity of memory to the effects of drugs. After the production of a brain lesion, the memory processing of a passive-avoidance task in mice gradually becomes sensitive to the effect of morphine, i.e., an improvement in retention performance is seen after 6 weeks, but not after 1 or 2 weeks. The results presented demonstrate that, even if they lead to no discernible changes in behaviour, plastic processes can still be detected by means of behavioural tests. PMID- 2594897 TI - Intranigral infusion of enkephalins elicits dyskinetic biting in rats. AB - Leu- and Metenkephalin (Lenk and Menk) and their more stable analogues D-Ala-Leu- and D-Ala-Metenkephalin (DALenk and DAMenk) as well as D-Ala-D-Leu- and D-Ala-D Metenkephalin (DADLenk and DADMenk) were infused bilaterally into substantia nigra in awake rats and oral movements were recorded for 90 min. DADLenk and DADMenk elicited dose-dependent biting dyskinesias with a chewing rate of about 90 jaw movements/min. DALenk produced a similar but weaker effect, whereas DAMenk, Lenk and Menk were ineffective in the doses given. These findings suggest a possible enkephalinergic mechanism underlying neuroleptic-induced tardive dyskinesias. PMID- 2594899 TI - Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats. AB - Learning/memory deficits in senescent animals are widely used as a tool to evaluate the therapeutic potential of agents for treatment of age-associated cognitive dysfunction. As assessed in the Morris water maze test, aged (21-24 months) rats showed a variable loss of spatial memory. Aged non-impaired rats performed as well as young subjects, while aged impaired rats exhibited a severe and persistent place-navigation deficit. Passive avoidance retention was similarly affected in the two aged subpopulations. Chronic oral administration of phosphatidylserine (50 mg/kg/day for up to 12 weeks), a pharmacologically active phospholipid, was found to improve both the spatial memory and the passive avoidance retention of aged impaired rats. Results are discussed with reference to the phosphatidylserine-induced improvement of age-associated deterioration of brain functions in rats. PMID- 2594898 TI - Diazepam and triazolam self-administration in sedative abusers: concordance of subject ratings, performance and drug self-administration. AB - The reinforcing effects of diazepam (DZ), triazolam (TZ) and placebo were examined in eight male subjects with histories of sedative abuse. DZ (40 or 80 mg), TZ (1.0 or 2.0 mg) and placebo were each individually available for oral self-administration using a double-blind within-subject design. After an initial sampling exposure, subjects could self-administer a single dose of drug on each of 6 days by completing a progressively increasing bicycle riding requirement. All subjects initially self-administered DZ and TZ but a decreasing number of subjects continued to self-administer drugs on the remaining days; there was no difference between DZ and TZ in the total number of self-administrations. Placebo was self-administered only by one subject on two occasions. Performance measures showed that TZ produced greater memory impairment than DZ and that DZ produced residual psychomotor impairment on the next day. With repeated dosing, evidence of tolerance was seen for both drugs on psychomotor and memory performance and subject ratings of drug liking. A few modest correlations of drug self administration and subject-ratings were obtained, suggesting some correspondence of subject verbal and drug self-administration behaviors, but these measures did not covary in a completely consistent manner. PMID- 2594900 TI - Contributions of hippocampus and neocortex to the expression of ethanol effects. AB - The distinctive effects of ethanol on behavior suggest that certain parts of the CNS may be especially sensitive to it. One of the primary candidates is the hippocampal formation. Damage to this structure mimics acute ethanol treatment across a wide variety of behavioral tasks and processes. The possibility of a hippocampal basis for ethanol psychopharmacology was examined in the present experiments. Chosen for behavioral analysis were relatively complex eight-arm radial maze tasks which have independently been shown to be sensitive to ethanol administration and hippocampal lesions. Measures included arm selection predictability, vigilance, and retardation of extinction. Bilateral hippocampal lesions or ethanol injection (1.5 g/kg, IP) produced similar effects. However, hippocampectomy did not disrupt ethanol's influence on any task. Comparatively, neocortical ablation, especially prefrontal, was quite effective in this respect. It blocked or reduced two of the drug's three behavioral effects examined here, without any strong influence of its own, and without altering blood alcohol concentration. PMID- 2594902 TI - Roles of intoxicated practice in the development of ethanol tolerance. AB - The development of tolerance to the motor impairment effect of ethanol was examined in separate groups of rats receiving and not receiving intoxicated practice. Tolerance to the motor impairment effect of ethanol developed whether or not rats received intoxicated practice during chronic ethanol treatment. Depending on the treatment dosage and test dose, intoxicated practice might enhance the level of tolerance attained. Tolerance to other effects of ethanol (hypothermia and narcosis) developed as a function of the treatment dosage. Intoxicated practice on the moving belt did not modify the development of tolerance to these effects of ethanol. Tolerance to the motor impairment effect of ethanol, however, was retained much longer in the intoxicated practice group following the termination of ethanol treatment. PMID- 2594901 TI - Does anxiety underly imidazole-induced behavioural effects in the rat? AB - Since behavioural symptoms (tremor, irritability, pilo-erection and shaking) induced by imidazole (IMID) in rats suggested an underlying modification of arousal and/or emotionality, further studies were performed in order to extend the range of behavioural influences of IMID. In the open-field test, IMID (37.5 300 mg/kg IP) inhibited crossing and rearing in a dose-dependent fashion, this effect being long lasting (about 3 h at 75 mg/kg). Yohimbine (YOH) (1, 5 and 10 mg/kg IP), described as anxiogenic and fear-inducing in animals and in man, when investigated in this same test, inhibited the activity of rats similarly to IMID. Since diazepam (0.5 and 1 mg/kg) but not clonidine (0.075 and 0.150 mg/kg IP) pretreatment reversed IMID- and YOH-induced hypomotility, the hypothesis that IMID effects in the open field might reflect an anxiety-like state was investigated by means of social interaction and x-maze, two tests considered highly specific for anxiety studies. The data obtained show that IMID depresses social interactions only at doses inhibiting motor activity; YOH, in our experimental conditions, produced a similar effect. In an elevated x-maze, with alternate open and closed arms, IMID (37.5 and 75 mg/kg) decreased the proportion of open-arm entries and the time spent in them, an effect prevented by diazepam pretreatment (1 mg/kg IP). Finally, mean arterial pressure (MAP) was assessed in anesthetized rats treated with IMID and YOH at doses equivalent as regards behavioural effects. MAP was increased by IMID whether IP or IV and decreased by YOH; moreover, YOH, as expected, antagonized clonidine-induced hypotension, while IMID was ineffective.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2594903 TI - Oro-facial dyskinesia and the sub-commissural part of the globus pallidus in the cat: role of acetylcholine and its interaction with GABA. AB - The possible role of cholinergic mechanisms in the sub-commissural part of the globus pallidus (scGP) in the induction of oro-facial dyskinesia (OFD) was studied in cats. Local injections of the cholinergic agonist carbachol into the scGP elicited tongue protrusions in a dose dependent way (100-1000 ng/0.5 microliters). The effect elicited by 1000 ng carbachol was selectively antagonized by the cholinergic antagonist scopolamine (10 micrograms/0.5 microliters); this dose of scopolamine was ineffective when injected alone. The tongue protrusions resulted from both normal and abnormal movements: whereas normal movements simply consisted of protruding the flat tongue, abnormal movements implied a variety of movements, especially curling upwards the lateral side(s) or tip of the tongue inside or outside the oral cavity. The abnormal carbachol-induced tongue protrusions formed part of a syndrome marked by dyskinetic movements of the muscles of the eye, ear and cheek, and were identical to those seen previously after local injections of picrotoxin (250-500 ng). Intra pallidal injections of the abovementioned dose of scopolamine had no effect on the tongue protrusions induced by local injections of 375 ng picrotoxin. However, local injections of 100 ng muscimol, which was previously found to attenuate significantly the effect of 375 ng picrotoxin and which was ineffective when injected alone, significantly attenuated the tongue protrusions induced by local injections of 1000 ng carbachol. These data suggest that the cholinergic effects are mediated via a GABAergic mechanism, but not vice versa. The results are discussed in view of GABAergic and anti-cholinergic therapies used in oro-facial dyskinesia. PMID- 2594904 TI - A comparison of calcium antagonists and diazepam in reducing ethanol withdrawal tremors. AB - The calcium antagonists nimodipine and dantrolene were compared with diazepam in an animal model of tolerance and physical dependence upon ethanol. Nimodipine and dantrolene were both effective in suppressing withdrawal tremors but diazepam was clearly superior to both agents. These results suggest that the ethanol withdrawal syndrome is only partially mediated by increased calcium flux. PMID- 2594905 TI - Changing environmental cues reduces tolerance to nicotine-induced anorexia. AB - Male rats on a 22-h food deprivation schedule were injected daily with a low dose of nicotine and allowed to drink sweetened milk for 10 min in a test cage in the colony room. Nicotine initially suppressed milk intake but complete tolerance developed within 10 days so that the amount of intake did not differ from saline controls. The role of temporal cues was tested on the next day by changing the timing of cues, and omitting others that normally preceded nicotine injection while keeping constant the physical environment within which injection and testing took place and the drug-test interval. Changing the timing of injection significantly suppressed milk intake. These results show that tolerance to the anorectic effects of a low dose of nicotine is partially dependent on the presence and timing of cues associated with tolerance acquisition. PMID- 2594906 TI - Smoking and human information processing. AB - There is much evidence which indicates that smoking improves various aspects of human information processing (Wesnes 1987). The aim of the present study was to elucidate the stages of human information processing which are improved after cigarette smoking. Twelve regular smokers were tested on three cognitive tasks using a repeated measures design. Tasks used were: rapid visual information processing (RVIP), digit symbol substitution (DSST), and inspection time (IT). Performance parameters derived from these were intended to index different stages of the information processing sequence. Only those measures which involved a motor component were improved after smoking: response time on the RVIP task (P less than 0.025) and DSST performance (P less than 0.1). These findings suggest that central cholinergic pathways are involved in the late, response-related stages of the processing sequence. PMID- 2594907 TI - Divided attention performance in cannabis users and non-users following alcohol and cannabis separately and in combination. AB - The effect of delta 9-tetrahydrocannabinol (delta 9-THC) and alcohol, singly and in combination, on divided attention performance was investigated in cannabis users and non-users who were matched for alcohol use. Both cannabis and alcohol produced decrements in central and peripheral signal detections. Drug and alcohol effects were greater for signal presentations in the periphery. Cannabis users were less impaired in peripheral signal detection than non-users while intoxicated by cannabis and/or alcohol. These findings suggest the development of tolerance and cross-tolerance in regular cannabis users and/or the ability to compensate for intoxication effects. PMID- 2594908 TI - Assessing pentobarbital preference in normal volunteers using a cumulative dosing procedure. AB - Preference for pentobarbital was assessed in 12 normal healthy volunteers using a seven-session cumulative dosing choice procedure. On the first four sessions subjects sampled the drug and a placebo, and on the last three sessions they chose the substance they preferred. During each of the sampling sessions they ingested, at 30-min intervals, five capsules containing either pentobarbital (30 mg per dose) or placebo. During the choice sessions subjects first chose which capsules they preferred to take (drug or placebo), and then took from one to seven of these capsules, separated by 30 min between ingestions. Self-report measures of subjective effects were obtained at regular intervals during each session. Subjects chose the pentobarbital-containing capsules on average 52% of choice sessions, and ingested an average total dose of 132 mg. Although the drug produced only modest, sedative-like subjective and behavioral effects and there was little evidence of euphoric effects in the group as a whole, individual differences in drug liking and choice were observed. The results are discussed in terms of variables that affect the reinforcing effects of pentobarbital in normal volunteers, and they are contrasted to previous findings using this procedure with other sedative drugs. PMID- 2594909 TI - Reply to J. R. Hughes, S. T. Higgins, and W. K. Bichel: behavioral "properties" of drugs. PMID- 2594910 TI - Infusions of cholecystokinin octapeptide into the ventral tegmental area potentiate amphetamine conditioned place preferences. AB - Cholecystokinin (CCK) and dopamine (DA) coexist in both cell body and terminal areas of a mesolimbic pathway that projects from the ventral tegmental area (VTA) to the nucleus accumbens (N ACC). Autoradiography reveals extensive CCK binding sites in the N ACC, but not in the VTA. However, iontophoresis of CCK into the VTA results in activation or deactivation of DA neuronal firing rates, and bursting activity (depending on the dose of CCK administered). CCK could have neuromodulatory effects on mesolimbic DA neurons. In two studies, behavioral effects of infusions of CCK into the VTA were examined in the conditioned place preference (CPP) paradigm. The CPP paradigm is a behavioral test used to assess reinforcement induced by drug administration. Drugs with reinforcing properties can condition preferences for novel environments. CCK infusions into VTA (0.0, 0.04, 0.4, and 4.0 ng/cannula) potentiated amphetamine CPPs in a dose-dependent linear manner. CCK infusions by themselves did not have significant effects in the CPP paradigm. Results indicate a neuromodulatory role for CCK on the neuronal mechanisms that mediate the reinforcing effects of amphetamine. Results also implicate sites of action for CCK in the VTA. PMID- 2594911 TI - Anti-conflict efficacy of buspirone following acute versus chronic treatment. AB - In many animal studies, acute treatment with the novel anxiolytic agent buspirone exhibits only minimal "anxiolytic efficacy" (i.e., increases in punished responding) when compared to benzodiazepines and barbiturates. The present studies examined the effects of acute pre-test challenges with buspirone in subjects receiving chronic post-test buspirone or saline treatments. Chronic post test treatment with buspirone (4 mg/kg/day for 4 weeks, followed by 8 mg/kg/day for 12 weeks) did not significantly affect CSD behavior. Consistent with previous reports, acute pre-test administration of buspirone (0.125-2 mg/kg, IP) to subjects receiving chronic post-test saline treatment resulted in only a modest anti-conflict effect in the CSD paradigm (approximately ten shocks over control). In contrast, subjects chronically treated with buspirone exhibited a dramatically greater anti-conflict effect following acute challenge with buspirone (up to 40 shocks over control). These data are consistent with the hypothesis that the full anxiolytic efficacy of buspirone requires repeated administration. PMID- 2594912 TI - Relationship between initial sensitivity, acute tolerance and chronic tolerance to ethanol in a heterogeneous population of Swiss mice. AB - Acute and chronic tolerance to ethanol hypothermia as a function of the initial sensitivity were examined in a heterogeneous population of Swiss mice. Based on their day 1 hypothermic response to a challenge dose of ethanol (4 g/kg, IP), 60 mice were divided into three groups: high responders (HR: delta Tmax 6.5-9 degrees C, n = 14); medium responders MR: delta Tmax 4.75-6.25 degrees C, n = 31); and low responders (LR: delta Tmax 3-4.5 degrees C, n = 15). Animals were injected once daily (between 9 and 11 A.M.) with 4 g/kg ethanol (20% w/v) for a period of 7 days. Testing was repeated on days 3 and 7 after the administration of the same dose of ethanol. The HR group showed the highest degree of chronic tolerance to ethanol hypothermia, followed by the MR group, while the LR group developed no chronic tolerance. Acute tolerance was considered to be present when delta T was lower at the same blood alcohol concentration (BAC), or BAC was higher at the same delta T, at later times in the same mouse. On days 3 and 7, the HR and MR showed acute tolerance, while the LR did not. Although metabolic tolerance to ethanol was detected in all three groups, ethanol metabolism played a minor role in initial sensitivity and acute and chronic ethanol tolerance. PMID- 2594913 TI - Nicotine maintains robust self-administration in rats on a limited-access schedule. AB - Intravenous nicotine maintained substantial responding on the drug-reinforced lever with a limited-access, fixed-ratio 5 schedule of self-administration. Responding demonstrated the expected pharmacological sensitivity; it was dose dependently reduced by pre-session treatment with either nicotine or mecamylamine but not with hexamethonium. In addition, responding was dependent on the size of the unit dose, with maximum values occurring at 0.01 and 0.03 mg/kg/infusion. Self-administration behavior decreased at doses both above and below these, and extinction followed the substitution of saline for nicotine. Total session drug intake increased with unit dose up to a maximal value of approximately 0.5 mg/kg at 0.03 mg/kg/infusion, but did not increase further at the 0.06 mg/kg/infusion dose. A decrease in the time-out duration at the dose of 0.03 mg/kg/infusion also did not change the total session intake of nicotine. It is suggested that nicotine intake is controlled both by the total amount of drug obtained and by the magnitude of the unit dose. These results demonstrate that intravenous nicotine can maintain substantial self-administration behavior in rodents. PMID- 2594914 TI - Tolerance to ethanol's disruptive effects on operant behavior in rats. AB - The effects of pre-session and post-session daily ethanol injections on the development and loss of tolerance to ethanol's effects on fixed ratio operant performance in rats was assessed using a cumulative dosing procedure. Daily pre session ethanol administration produced a greater decrease in ethanol sensitivity than did daily post-session ethanol. Both tolerance effects persisted for at least 1 month after the chronic injection phase. No changes in ethanol sensitivity were apparent in the saline control group and no changes in estimated blood ethanol levels were found after the chronic treatments. The post-session ethanol groups displayed a performance decrement during the initial segment of the chronic injection period, but improved significantly across the chronic phase. These data suggest that some delayed effect of ethanol initially impaired performance but that tolerance to this ethanol effect also occurred and probably contributed to the decline in ethanol sensitivity seen in these groups. Compensatory learning as the mechanism for tolerance development in the pre session and post-session ethanol groups was supported by the finding of no change in ethanol sensitivity in rats exposed to comparable daily ethanol without any concurrent operant task on which the direct, immediate, or indirect, delayed ethanol effects could operate. PMID- 2594915 TI - Effect of instructions and nicotine on smoking cessation, withdrawal symptoms and self-administration of nicotine gum. AB - Seventy-seven smokers quit smoking and were randomly assigned to a 3 x 2 design contrasting instructions (told received nicotine gum versus told received placebo gum versus not told which gum received) and receipt of nicotine (received nicotine gum versus received placebo gum). Both being told one received nicotine and actual receipt of nicotine increased the number of days abstinent and decreased the number of cigarettes smoked (P less than 0.05). Receipt of nicotine but not instructions appeared to influence withdrawal (P = 0.06). Instructions but not receipt of nicotine appeared to influence craving (P = 0.08), gum self administration (P = 0.06) and reported helpfulness of the gum (P = 0.02). Neither nicotine nor instructions influenced side-effects. Instructions and nicotine interacted in several ways. For example, nicotine appeared to increase abstinence in the blind and told placebo conditions more than in the told nicotine condition (P less than 0.05). Our results suggest the effects of instructions and nicotine 1) are not mutually exclusive, 2) vary across dependent variables and 3) can interact such that instructions modify the therapeutic and subjective effects of nicotine. PMID- 2594916 TI - Involvement of noradrenergic system in a remarkably rapid tongue clonus produced by acute hypnotic doses of ethanol in Fischer F344 rats. AB - Ethanol (2.95 g/kg, IP) eliminated the righting reflex and induced vigorous tongue clonus spontaneously or following tactile tongue stimulation in Fischer F344 rats. Responses normally lasted 30-60 min, and was reinstated by tactile stimulation in those cases where it subsided quickly. Sub-hypnotic (1.95 g/kg) or high (3.95 g/kg) doses failed to elicit clonus, even after tactile stimulation. A lipophilic alpha 1-adrenergic agonist (St 587) promptly initiated tongue clonus in rats treated with a 3.95 g/kg dose of ethanol. Prazosin, a selective alpha 1 adrenergic antagonist, blocked clonus, while the dopamine selective antagonist pimozide failed to modify this response. We infer an alpha 1-adrenergic effect in which norepinephrine is released by ethanol. PMID- 2594917 TI - Time course of amphetamine-induced locomotor stereotypy in an open field. AB - Gamma (gamma) is a recently proposed statistic that quantifies and describes the repetitive patterns of locomotion (locomotor stereotypy) exhibited by amphetamine treated rats in an open field. The time-course of locomotor stereotypy after 1, 2, 3, and 4 mg/kg amphetamine was investigated in this research. Locomotor stereotypy was often evident during the first observation period after amphetamine. Lower doses of amphetamine produced qualitatively different locomotor stereotypy than higher doses. Rats given higher doses of amphetamine exhibited locomotor stereotypy during the "hyperactivity" phase of the three phase response produced by higher doses of amphetamine (hyperactivity; absence of locomotions, increased sniffing, biting etc.; hyperactivity). Contrary to expectations, rats injected with 2 mg/kg amphetamine exhibited the highest and most sustained increase in gamma. We conclude that locomotor stereotypy is an important component of the behavioral effects of amphetamine in rats. Whether locomotor stereotypy and focused stereotypy are similar phenomena is still unclear. PMID- 2594918 TI - 3H-spiroperidol binding in human temporal cortex (Brodmann areas 41-42) occurs at multiple high affinity states with serotonergic selectivity. AB - 3H-Spiroperidol labels multiple high affinity states with serotonergic selectivity in human prefrontal cortex and with dopaminergic selectivity in human caudate and putamen. The characteristics of the binding of this ligand in human temporal cortex have not been previously described. Brodmann areas 41-42 in the temporal cortex are associated with primary auditory sensation and, in epileptics, with auditory hallucinatory experiences. We found that in this region of the human brain, antipsychotic ligands bind at multiple high affinity states, the majority of which exhibit serotonergic, rather than dopaminergic, selectivity. Dose-response data is best resolved by a three-site fit. Results of the co-analysis of dose-response data with saturation data indicates that two of the 3H-spiroperidol affinity states may represent the high and low affinity states of the serotonin (5HT)2 receptor, while a third affinity state may represent the 5-HT1A receptor. PMID- 2594919 TI - Administration of triazolam prior to recovery sleep: effects on sleep architecture, subsequent alertness and performance. AB - The effects of triazolam (0.125, 0.25, and 0.5 mg) versus placebo on recovery sleep staging, subsequent alertness and psychomotor performance were evaluated in humans. Forty-five healthy male subjects were deprived of sleep for 24 h, then administered a single dose of triazolam or placebo using a double-blind procedure. Subjects then attempted to obtain recovery sleep under non-sleep conducive conditions (sitting upright in a well-lit, crowded chamber) for the next 6 h, followed by 18 more hours of sleep deprivation. During all sleep deprivation periods subjects were tested bihourly on a performance assessment battery which included symbol digit modalities tests (SDMT), four-letter search (FLS), logical reasoning (LR), time estimation (TE), visual vigilance (VV), and short term memory (STM) tasks. Sleepiness levels were measured objectively with multiple sleep latency tests (MSLT) and subjectively with the Stanford Sleepiness Scale (SSS). Compared to placebo, all doses of triazolam resulted in increased amounts of stage 3-4 sleep, and the 0.5 mg dose significantly reduced awakenings (Ps less than 0.05). Although subjects receiving triazolam averaged 21-42 min more total sleep time (TST) than subjects receiving placebo, differences in TST were not statistically significant. Apparent triazolam-mediated benefits to sleep quality resulted in no obvious improvements in performance or alertness levels during subsequent sleep deprivation. It was concluded that the increases in stage 3-4 sleep amounts were most likely due to triazolam-mediated increases arousal thresholds, and the triazolam mediated changes in sleep parameters obtained in the present study were not indicative of substantial changes in the recuperative value of sleep. PMID- 2594920 TI - Cocaine enhances memory storage in mice. AB - Mice were trained on a one-trial inhibitory avoidance task and given immediate post-training intraperitoneal injections of cocaine (0.03-1.00 mg/kg). On a retention test 24 h later, the retention latencies of mice given the 0.10 mg/kg dose were significantly higher than those of the controls. The effect of cocaine on retention was time-dependent: retention latencies were not altered in animals given cocaine 60 min after training. Administration of cocaine (0.1 mg/kg) prior to the retention test did not modify the retention performance of mice that received either saline or cocaine (0.1 mg/kg) immediately post-training. The findings suggest that cocaine affects retention by influencing post-training processes involved in memory storage. PMID- 2594922 TI - Effects of d-amphetamine and methylphenidate on hyperactivity produced by neonatal 6-hydroxydopamine treatment. AB - Neonatal intracisternal administration of 6-hydroxydopamine (6-OHDA, 50 micrograms on day 1 after birth) caused a marked hyperactivity when the rats were tested as adults. These rats also showed severe DA depletions in striatum and nucleus accumbens. Pretreatment with the noradrenaline (NA) uptake inhibitor desipramine provided protection against NA depletion in frontal cortex and nucleus accumbens. Pretreatment with DA uptake inhibitors, amfolenic acid or GBR 12909, before 6-OHDA, provided full protection against DA depletion but produced marked NA depletion in frontal cortex. These rats did not demonstrate any degree of hyperactivity. Low doses of d-amphetamine (0.25 mg/kg SC) or methylphenidate (1 mg/kg SC) reversed the hyperactivity in DA-depleted rats but increased motor activity in vehicle-treated and NA-depleted rats. Higher doses of d-amphetamine (1 mg/kg) or methylphenidate (4 mg/kg) produced potentiated levels of locomotion but attenuated levels of rearing in DA-depleted animals. The results further suggest the utility of the neonatal DA lesion in rats as a potential animal model for derivation of therapeutic agents that may be efficacious in the treatment of the hyperkinetic syndrome. PMID- 2594921 TI - Cholinergic stimulation of the ventrolateral striatum elicits mouth movements in rats: pharmacological and regional specificity. AB - Cholinomimetic drugs are known to induce changes in perioral behavior in rodents, characterized primarily by "purposeless" chewing movements, but little is known about their central sites of action. Using observational methods, the effects of direct microinfusion of a mixture of physostigmine and acetylcholine (PS/Ach, 0, 0.5, 2.5, 5.0 micrograms of each in 0.5 microliter saline) into the ventrolateral striatum (VLS) were assessed. Cholinergic stimulation of this region produced a dose-dependent induction of mouth movements, characterized by chewing movements, jaw opening and closing, tongue protrusions and jaw tremors. These movements were not directed toward any stimulus. In some rats, cholinergic stimulation of the VLS also induced stereotyped self-biting, although this effect was less prominent and of shorter duration. Induction of mouth movements by cholinergic stimulation of the VLS was blocked by prior administration of atropine, either systemically (50 mg/kg) or directly into the VLS (10 micrograms). Systemic administration of methylatropine (50 mg/kg) did not block the mouth movements. Pretreatment with haloperidol (2.5 micrograms into VLS) had no effect on PS/Ach-induced mouth movements. Infusion of PS/Ach (0, 2.5, 5.0 micrograms) into the dorsolateral or ventromedial striatum did not produce significant changes in oral behavior, although the level of mouth movements was somewhat higher at the medial site. The three sites studied were also differentiated with respect to spontaneous motor behaviors (locomotion and rearing) following direct cholinergic stimulation. These findings are considered as further evidence for the role of the ventrolateral striatum in oral motor behavior. PMID- 2594923 TI - Interaction between accumbens D1 and D2 receptors regulating rat locomotor activity. AB - The effect of intra-accumbens injections of various dopaminergic agonists and antagonists on the rat locomotor activity has been evaluated in automated open fields. Locomotor stimulation has been observed after local administration of d amphetamine (10 micrograms), apomorphine (10 micrograms), as well as of solution containing the D1 agonist SKF 38 393 and D2 receptor agonist LY 171 555 (quinpirole) in doses (10 and 4 micrograms, respectively) which were inactive when both drugs were administered separately. On the other hand separate injections of metoclopramide (0.1 microgram) and SCH 23 390 (0.5 microgram) (D2 and D1 receptor antagonists) very potently inhibited animals' locomotor activity. The data indicate that concomitant stimulation of both accumbens D1- and D2 receptor related mechanisms is a necessary condition to increase rat motility. Moreover, it seems that accumbens D1 receptors may be differently involved in the control of facilitatory versus inhibitory motor processes. PMID- 2594924 TI - The effects of clonidine and yohimbine on human information processing. AB - The effects of clonidine and yohimbine on human information processing were tested in six normal volunteers ages 18-30 years. Subjects were tested in a pre post design with sessions conducted at weekly intervals. Three drug conditions were: Placebo (lactose), 0.2 mg clonidine, and 30 mg yohimbine. Two choice reaction time (RT) tasks were used. One was a stimulus evaluation-response selection task (SERS) that has been shown to be sensitive to d-amphetamine, methylphenidate and scopolamine. The other task was to assess stimulus pre processing and used spatial frequency as a discriminative stimulus. The principle finding was that clonidine slowed RT; this effect was significant for both tasks. In contrast, yohimbine tended to speed RT, but the effects were significant only for the spatial frequency task on some analyses while not for others. RTs to high spatial frequency stimuli were speeded more than for low spatial frequency. The effects of these two NE drugs were compared with findings with d-amphetamine and scopolamine and interpreted within the framework of a serial information processing model proposed by Callaway (1983). Specifically, it is suggested that yohimbine and clonidine affect an early pre-processing stage. PMID- 2594925 TI - Uptake of amino acids and ammonia at mid-gestation by the fetal lamb. AB - Fetal uptakes of amino acids and ammonia via the umbilical circulation were measured in single pregnant ewes at mid-gestation (range 66-81 days). There were significant net fluxes from placenta to fetus of ammonia and twelve amino acids (in decreasing order: glutamine, glycine, alanine, proline, lysine, arginine, threonine, valine, leucine, tyrosine, asparagine, isoleucine) and net fluxes from fetus to placenta of glutamate and serine. The estimated serine flux was 139 mumol day-1 (g fetal dry wt)-1. Comparison with late gestation data indicated a similar pattern of amino acid exchange. However, the relatively large placental uptake of fetal serine was a distinctive feature of mid-gestation. The net fetal uptake of amino acid nitrogen was 2.83 +/- 0.66 micrograms N (mumol O2 uptake)-1, or 18 mg N day-1 (g dry wt)-1. This uptake was similar in magnitude to the combined fetal requirements for nitrogen accretion and urea synthesis and represented approximately 32 and 43% of fetal carbon and energy requirements, respectively. PMID- 2594926 TI - Fluid balance during heat stress in lactating goats. AB - Fluid balance and thermoregulation were studied during an acute heat load (maximal daily temperature, 38 +/- 1 degrees C; night temperature 27 +/- 1 degrees C) in six goats during lactation and non-lactation. The goats had free access to water for 1 day, followed by 29.5 h of water deprivation and then water was returned. With water available the goats increased water intake and urinary and milk water losses, while plasma and milk osmolality decreased. Water deprivation caused plasma osmolality and vasopressin concentration to increase most in lactating goats. Milk osmolality rose to values similar to plasma osmolality. Plasma cortisol increased in lactating goats at the end of dehydration. Renal Na+ excretion increased during dehydration in lactating goats. Evaporative heat loss was larger in lactating goats when hydrated, but became less than in non-lactating goats during dehydration. Lactating goats exhibited higher respiratory frequency and rectal temperature than non-lactating goats. In conclusion, our results show that goats increase the water turnover during heat stress if allowed to drink ad libitum, but when they are deprived of water lactating goats reduce water loss in urine, milk and by evaporation, and rectal temperature reaches higher levels than in non-lactating animals. This saving of water could allow milk production to be maintained for a longer time during heat stress. PMID- 2594927 TI - Injury to skeletal muscles of mice by forced lengthening during contractions. AB - Our purpose was to determine the amount of injury to extensor digitorum longus (EDL) and anterior tibial (ATB) muscles of mice from 1 h to 30 days following passive shortening and lengthening, shortening contractions and lengthening contractions. The shortening-lengthening cycle was of 600 ms duration and was repeated every 5 s for 30 min. Contractions were produced during either the shortening or lengthening phase with stimulation at 100 Hz for 300 ms. The amount of injury was evaluated by the decrease in the number of fibres in a cross section of the muscle and in the maximum isometric tetanic force (Po). Passively shortened and lengthened and actively shortened EDL and ATB muscles showed no evidence of injury. At 3-5 days after lengthening contractions, EDL and ATB muscles showed an inflammatory response. At 3-5 days, the number of fibres in the cross-section of the injured EDL muscles was 65% of that of the contralateral control EDL muscle, whereas no change was observed in the number of fibres in the injured ATB muscles. By 3 days, the presence of myoblasts, myotubes and central nuclei indicated regeneration of fibres. One hour after shortening contractions, the Po of EDL and ATB muscles decreased to about 75% of the contralateral control value, but recovered completely by 3 days. In contrast, 1 h after lengthening contractions the Po of EDL and ATB muscles decreased to 52 and 40% respectively of the contralateral control value and then both recovered to about 65% within 3 h. For the ATB muscle, the Po showed a secondary decrease to 49% of the contralateral control value at 1 day and for the EDL muscle, to 47% at 3 days. Each muscle recovered gradually and by 30 days the number of fibres and the Po of the injured muscles were not significantly different from values for contralateral control muscles. PMID- 2594928 TI - Interactions between intracellular pH and calcium in single mouse neuroblastoma (N2A) and rat pheochromocytoma cells (PC12). AB - Intracellular pH (pHi) was measured at the tips of extending neurites and in the corresponding cell bodies of single cultured mouse neuroblastoma (N2A) and rat pheochromocytoma cells (PC12) using the fluorescent dye 2,3-di-cyanohydroquinone (DCH). It was observed that pHi at the tip of an extending neurite was consistently 0.2-0.3 pH units higher than pHi in the cell body. Experiments performed on whole cells to establish the types of cellular mechanism which could be responsible for such regional differences demonstrate the presence of Na+-H+ exchange and Cl- HCO3- exchange in these cells. Since regional variations in Ca2i+ have been reported between neurites and the cell body, experiments were performed to examine the possible interactions between pHi and Ca2i+. Intracellular calcium was measured using the fluorescent Ca2+-sensitive dye Indo 1. An increase in pHi, on application of NH4Cl, resulted in a transient elevation of Ca12i+. On subsequent acidification, on removal of NH4Cl, there was a further transient increase in Ca2i+. These changes in Ca2i+ were also present in solutions with low calcium suggesting that Ca2i+ is mobilized from within the cell. The results are discussed in terms of possible mechanisms whereby the extension and retraction of cell processes could be influenced by Ca2i+ and modulated by pHi. PMID- 2594929 TI - Reflex actions of selective stimulation of sural nerve C fibres in the rabbit. AB - Selective electrical stimulation of the non-myelinated C fibres of the sural nerve in the decerebrated, spinalized rabbit evoked long-latency (76-160 ms), long-lasting (greater than 100 ms) reflex responses in the ipsilateral ankle extensor gastrocnemius medialis (GM). Activation of the same fibres elicited little or no response from the ipsilateral knee flexor semitendinosus (ST). Reflex responses were evoked in both GM and ST muscle nerves by stimulation of the A beta afferents of the sural nerve. The A beta-elicited reflex in GM was enhanced, and that in ST depressed by prior activation of sural nerve C fibres. Strychnine, but not picrotoxin or mecamylamine, blocked C fibre-induced inhibition of the flexor reflex. Pinching the heel with serrated forceps produced an immediate reflex discharge in GM motoneurones, whereas ST responded upon termination of the stimulus. Pinching the second toe evoked reflex activity in ST but not in GM. After strychnine (0.5 mg kg-1), both sets of motoneurones responded simultaneously to stimulation of either the heel or the toe. These data show that sural and other afferent fibres from the heel excite ipsilateral GM motoneurones and inhibit ST reflex responses. One interpretation of these findings is that fine sural afferents activate parallel inhibitory and excitatory pathways, of which the former is sensitive to strychnine and therefore probably mediated by glycine. PMID- 2594930 TI - Age-related effects of fatigue and recovery from fatigue in rat medial gastrocnemius muscle. AB - Force-velocity, power-velocity and unloaded shortening data were obtained from in situ medial gastrocnemius muscle-tendon complexes (stimulated at 60 Hz) with intact circulation of mature male rats (approximately 125 days old). Measurements were carried out at the end of a long (15 s) contraction (fatigued muscles) or with a short (1 s) contraction either in the fresh state (fresh muscles) or in muscles which had recovered for 15 min after a long contraction. Compared to the fresh state fatigue reduced isometric force by 57%, maximal shortening velocity by approximately 40% and maximal power output by 81%. These reductions were similar to data previously obtained with younger rats (40 days old). However, the velocity data of the muscles which had recovered for 15 min after a long contraction showed a greater reduction in the mature rats. This difference between the two age groups together with a difference in the changes in the initial parts of the isometric force time curves suggest an age-dependent response of the fast-fatigable fibre population of these mixed muscles. In a separate series of experiments the underlying mechanism of the recovery from fatigue was studied in a group of young rats. Fatigue was induced with five long (15 s) contractions (each at 5 min intervals). The recovery of isometric force and power output was monitored with short contractions which indicated a plateau of recovery but the absolute values were still reduced after 60 min (85 and 71% of prefatigue values, respectively). Phosphocreatine concentration recovered rapidly, whereas the ATP concentration was still markedly reduced after 1 h of recovery. The time courses of recovery of inosine-5'-monophosphate (IMP) and lactate concentrations resembled those of force and power output. Thus it is possible that age-dependent differences in IMP and/or lactate production may play a role in fatigue and recovery from fatigue. PMID- 2594932 TI - The influence of left ventricular pressure on the vascular responses to changes in carotid sinus pressure in anaesthetized dogs. AB - The aim of this study was to determine whether the degree of stimulation of left ventricular receptors influenced the sensitivity of the carotid sinus baroreceptor reflex. In anaesthetized dogs, the stimulus to left ventricular receptors was changed by changing aortic root and hence ventricular systolic pressure, using a preparation in which the applied pressure did not distend the aortic arch and in which left atrial pressure was controlled. A large step increase in either carotid or left ventricular pressure resulted in vasodilatation both in a perfused hindlimb and in the remainder of the systemic circulation and resulted in a reduction in the response to a change in pressure in the other area. The stimulus-response curves, relating limb and systemic perfusion pressures to small step changes in carotid sinus pressure, were displaced downwards at high left ventricular pressures. However, the curves remained parallel indicating the absence of an interactive effect. These results indicate that the vascular responses to changes in carotid and ventricular pressures show simple additive summation. PMID- 2594931 TI - Metabolism and inactivation of gastrin releasing peptide by endopeptidase-24.11 in the dog. AB - The purpose of this investigation was to examine the metabolism and inactivation of gastrin releasing peptide 10 (GRP10) by endopeptidase-24.11 prepared from the stomach wall. GRP10 was metabolized in vitro by gastric endopeptidase-24.11. The metabolites were purified by high-pressure liquid chromatography and identified as (1-8) GRP10 and (9-10) GRP10 by amino acid analysis, indicating hydrolysis of the His8-Leu9 bond. The intravenous administration of GRP10 to conscious dogs stimulated gastrin release, gastric acid secretion, pancreatic protein secretion and pancreatic bicarbonate secretion. Incubation of GRP10 with endopeptidase 24.11 significantly diminished the biological activity of the digests compared to control digests containing heat-inactivated enzyme. This effect was abolished by the enzyme inhibitor phosphoramidon. It is concluded that endopeptidase-24.11 from the stomach metabolizes and inactivates GRP10. PMID- 2594933 TI - The effects of acute and chronic exposure to ethanol on glucose uptake by rat jejunal brush-border membrane vesicles. AB - Rats were pair-fed for 28-32 days a nutritionally adequate liquid control diet or an isocaloric diet containing ethanol (5% v/v). Brush-border membrane vesicles were prepared from jejunal mucosa and Na+-dependent D-glucose accumulation was measured using sugar concentrations of 0.2-1.0 mmol l-1. In separate experiments the effects of acute ethanol exposure on glucose uptake by vesicles prepared from chow-fed rats were determined. Chronic ethanol ingestion enhanced Na+-gradient dependent glucose uptake. In contrast, incubation of vesicles with alcohol (4% v/v), reduced active uptake of the sugar. PMID- 2594935 TI - Attenuation of the acute cardiovascular responses to haemorrhage by tissue injury in the conscious rat. AB - A moderate haemorrhage of 0.75 +/- 0.09 ml (100 g body weight)-1 (11.1 +/- 1.3% of estimated blood volume) in the conscious rat produces a tachycardia, possibly mediated by the baroreflex, which serves to maintain mean arterial blood pressure. A severe haemorrhage of 1.20 +/- 0.06 ml (100 g)-1 (greater than or equal to 19.5 +/- 1.5% of estimated blood volume) produces a bradycardia and marked hypotension. The bradycardia is reflex in nature and is due to an increased vagal efferent activity to the heart. This bradycardia is markedly attenuated in animals treated neonatally with capsaicin to render them deficient in C fibres, suggesting that peripheral C fibres (possibly cardiac C fibre afferents, Oberg & Thoren, 1972) are of importance in the bradycardic response to a severe haemorrhage. Concomitant tissue injury produced by bilateral hindlimb ischaemia in a group of animals with normal C fibre afferents markedly attenuates or abolishes the bradycardia and reduces the fall in mean arterial blood pressure produced by severe haemorrhage, although the tachycardia seen with smaller haemorrhages is affected to a much lesser degree. It is concluded that tissue injury can modify the cardiovascular response to a severe haemorrhage, possibly by interacting with the reflex effects of stimulating cardiac C fibre afferents. PMID- 2594934 TI - The effect of anaesthesia and standard clearance procedures on renal function in the rat. AB - Renal function was assessed in unrestrained conscious rats during either their active period (i.e. the hours of darkness) or their inactive period. On the following day, measurements were repeated after Inactin anaesthesia and preparation for clearance studies. In rats anaesthetized during their active period, preparation for clearance studies had no effect on inulin clearance (used as a measure of glomerular filtration rate), lithium clearance (used as an estimate of end-proximal fluid delivery) or fractional lithium excretion. In rats anaesthetized during their inactive period, the same procedures resulted in increases in all three variables, to reach values indistinguishable from those in animals studied during their active period. In both groups of rats there were increases in the fractional reabsorption of sodium and water in the distal nephron and in the urinary excretion of potassium. It is concluded that in anaesthetized rats prepared for clearance studies, rates of glomerular filtration and proximal tubular reabsorption (as indicated by lithium clearance) are similar to those in conscious animals during their active period. PMID- 2594936 TI - Effect of the cessation of an infusion of vasopressin in acutely hypophysectomized anaesthetized dogs. AB - Stimulation of left atrial receptors in dogs anaesthetized with chloralose results in a reflex diuresis and a small decrease in the plasma concentration of vasopressin. It has been suggested that this diuretic response is solely mediated by the antidiuretic hormone, vasopressin (Gauer & Henry, 1976; Ledsome, 1985). The present investigation was designed to determine how these anaesthetized dogs, which are thought to be insensitive to changes in plasma vasopressin, respond to small decreases in plasma vasopressin similar to those observed during stimulation of left atrial receptors. In the event it was shown for the first time that it is possible to obtain a water diuresis in an anaesthetized animal in response to a small fall in the concentration of plasma vasopressin. In order to produce changes in plasma vasopressin similar to those seen during stimulation of left atrial receptors the pituitary gland was removed and an intravenous infusion of arginine vasopressin was given in eleven dogs anaesthetized with chloralose; a small decrease in plasma vasopressin was then produced by replacing the vasopressin with an infusion of saline for 30 min. A decrease in the plasma concentration of 1.29 pg cm-3 from a control concentration of 1.85 pg cm-3 resulted in a 96.7% increase in urine flow. The fall in concentration of vasopressin consequent upon stimulation of atrial receptors could, therefore, explain the water diuresis in the anaesthetized dog preparation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2594937 TI - Pre-pyloric mechanisms regulating gastric motor function in the conscious dog. AB - Reflex mechanisms regulating gastric motor function were studied in four conscious dogs, whose stomachs had been surgically divided into separate corporal and antral pouches. Interactions between the corpus and antrum were investigated in fasted animals by balloon distension of each region. During the quiescent phase (phase I) of the migrating motor complex (MMC), distending the corpus with volumes greater than 80 ml resulted in contractions of the corpus, which persisted for as long as the distending stimulus was applied. This corporal distension also initiated antral contractions which were greater if the antrum was moderately distended and also greater with a larger corporal distending volume up to 300 ml. Graded 5 ml inflation of the antrum during the quiescent phase of the MMC stimulated antral contractions. This antral response to antral distension was augmented when the corpus was inflated but was only statistically significant with antral volumes below 25 ml. Distension of the antrum with volumes greater than 12.5 ml caused inhibition of corporal contractions during both the active phase of a migrating complex or when stimulated by corporal inflation. The degree of inhibition was proportional to the distending stimulus and was present for the duration of the applied distension. For antral volumes of 50 ml the inhibition persisted for a variable time after the stimulus was withdrawn. The inhibition of corporal activity by antral distension was still effective after blocking acid secretion with cimetidine (100 mg), which would eliminate spillage of acid into the jejunum as a cause of the inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2594938 TI - Role of 1,25-(OH)2D3 during pregnancy; studies with pigs suffering from pseudo vitamin D-deficiency rickets, type I. AB - Biochemical parameters of Ca homeostasis in fetal and maternal plasma and placental transfer of Ca, Pi and vitamin D metabolites were measured during pregnancy and at parturition. Control pigs and pigs with inherited pseudo-vitamin D-deficiency rickets, type I (PVDR), which are devoid of renal calcitriol production, were used. Although sows with PVDR normally require treatment with massive doses of vitamin D at intervals of 4 weeks to stabilize Ca and Pi concentrations in plasma, these plasma parameters tended to normalize during the first 3 months of pregnancy when the vitamin D treatment was discontinued about 4 weeks before conception. In homozygote sows plasma calcitriol concentrations remained unphysiologically low and the 25OHD3 concentrations increased steadily during pregnancy reaching higher levels than those found in control sows. Despite hypocalcaemia and hypophosphataemia of the homozygote sows at term, fetal Ca and Pi concentrations were normal. This demonstrated a higher feto-maternal concentration gradient in PVDR pigs than in control pigs. It is concluded that maintenance of Ca and Pi homeostasis of the feto-maternal system, including active transplacental transport in pigs, is at least partly independant from calcitriol. PMID- 2594939 TI - Chloride-bicarbonate exchange in isolated rat pancreatic acini. AB - We have measured the intracellular pH (pHi) of single isolated rat pancreatic acini using the fluorescent dye dicyano-hydroquinone (DCH). Steady-state pHi was unaffected by either acetylcholine (10 microM), caerulein (10 nM) or secretin (1 nM), or by the anion exchange inhibitor DIDS (1 mM) and only changed by 0.32 units when extracellular pH was varied over the range from 6.8 to 8.4. However, replacing extracellular chloride with gluconate, such that the final bath chloride concentration was less than 20 mM, caused a marked alkalinization of pHi to a new steady-state value. The rate of pHi alkalinization under these conditions was bicarbonate-dependent, blocked by pre-incubation of the acini with 1 mM-DIDS, but unaffected by removal of extracellular sodium. These observations are consistent with the presence of a Cl- -HCO3- exchanger on rat pancreatic acinar cells. Since DIDS had no effect on steady-state pHi the anion exchanger is unlikely to play a role in pHi regulation. However, rat pancreatic acini secrete a NaCl-rich fluid and the Cl- -HCO3- a exchanger might function in parallel with Na+-H+ exchangers to provide a mechanism for chloride accumulation across the basolateral membrane of the acinar cells. PMID- 2594940 TI - Muscle tone around the human knee in paraplegia. AB - The thigh muscle tone of non-injured subjects and complete injury paraplegics has been investigated using torques, generated by a printed motor, to move the knee. The dynamic measure of resonant frequency (related to stiffness) together with a static measure of stiffness have shown the legs of non-injured subjects to respond non-linearly to decreasing torques. However, the complete paraplegics' legs did not respond non-linearly but showed constant resonant frequency and stiffness over the range of torques. Peak velocity at resonance (inversely related to damping) gradually increased with increasing torques in both groups. In addition, at a chosen baseline torque of 0.7 N m, resonant frequency and muscle stiffness were significantly lower and peak velocity significantly higher in the paraplegics compared to the non-injured subjects. Contrary to expectations the thigh muscles in established, complete paraplegia showed a lack of tonic EMG activity. In addition, whilst phasic stretch responses were occasionally seen there was no tonic activity in relation to continued stretch. Since muscles atrophy after paralysis, the smaller muscle bulk may contribute to the lower muscle tone. PMID- 2594941 TI - Kinetics of rapid 45Ca uptake into chick skeleton in vivo: effects of microwave fixation. AB - We have investigated uptake kinetics for 45Ca labels acutely administered as single intravenous injections into twelve-day-old chicks in vivo. Effects of microwave fixation on this process have also been studied. Rapid uptake of 45Ca was demonstrated into the skeleton with approximately 40% of injected label being found in the skeleton within the first 15 min. By 45 min tissue 45Ca levels had stabilized and showed little change during the following 90 min. Soft tissue isotope levels declined during the period from 3 to 135 min following injection. These data were obtained from animals in which tissue isotope levels were stabilized by fixation with microwaves at the point of killing by cervical dislocation. In animals where the microwave fixation step was omitted and tissues were dissected for counting at least 1 h after killing, 45Ca levels in both skeletal and soft tissues were 15-20% higher than in those from microwave groups during the period 3-15 min after injection. In a separate experiment, groups of chicks killed by cervical dislocation 3 min after isotope injection were fixed with microwaves at time intervals ranging from 0 to 45 min post-mortem. Isotope levels in femur increased with time and were significantly higher in groups in which fixation was carried out 12 and 45 min after death when compared with those fixed at the point of death. Data in calvarium reflected those in femur but were not statistically significant at the time intervals tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2594942 TI - Evidence for furosemide-sensitive Na+-K+-Cl- co-transport in lactating rat mammary tissue. AB - The transport of K+ (using 86Rb as tracer) by lactating rat mammary tissue slices has been studied in order to seek evidence for Na+-K+-Cl- co-transport. Potassium transport was inhibited by furosemide; the locus of inhibition was at a site other than the Na+:K+ pump. Replacing medium Cl- with NO3 reduced the bidirectional movement of K+; moreover, furosemide was without effect in a Cl- free medium. Sodium replacement by N-methyl-D-glucamine acted to reduce the loop diuretic-sensitive component of K+ uptake whilst concomitantly increasing K+ influx via an ouabain- and furosemide-resistant pathway. Potassium efflux was found to be transiently stimulated by Na+ ions; this was attenuated by furosemide. Potassium egress was markedly increased via a furosemide-insensitive pathway when salicylate was used to replace Cl-. The results are consistent with furosemide-sensitive Na+-K+-Cl- co-transport. PMID- 2594943 TI - Stoichiometry of net sodium and potassium fluxes mediated by the Na-K-Cl co transport system in ferret red cells. AB - The bumetanide-sensitive Na-K-Cl co-transport system in ferret red cells produces net movement of 1Na:1K. Tracer studies have misleadingly suggested a stoichiometry of 2Na:1K probably because the transporter mediates substantial Na Na exchange in these cells. PMID- 2594944 TI - A comparison of contractile function in large and small pulmonary arterial vessels of the rat. AB - The contractile function of rat pulmonary arterial vessels, ranging in internal diameter from 100 to 2000 microns, was studied in vitro using a small vessel myograph. It was found that vessels with a diameter of 200-400 microns produced considerably more force for a given intervention than those either smaller (less than 100-2000 microns) or larger (400-2000 microns). It is suggested that these vessels may play an important role in the generation of pulmonary vascular resistance. PMID- 2594945 TI - Fatigue of isolated mouse muscle due to isometric tetani and tetani with high power output. AB - The fatiguing effect of a series of isometric tetani and of tetani with shortening and maximum power output were compared using soleus and extensor digitorum longus muscle of mouse. Mean force in test isometric tetani after the series was reduced by up to 35% compared with pre-series controls. Tetani with shortening were always more fatiguing than isometric tetani. PMID- 2594946 TI - Tolbutamide reverses hypoxic pulmonary vasoconstriction in isolated rat lungs. AB - We have investigated the effects of tolbutamide on the hypoxic vasoconstriction of isolated, perfused rat lungs. We did this because lowered ATP may link hypoxia and constriction, and tolbutamide mimics the effects of ATP in other tissues by blocking ATP-sensitive potassium (ATP-K) channels. Pulmonary vasoconstriction, induced by lowering the oxygen of the gas ventilating the lungs from 95 to 2%, was always reduced or abolished by tolbutamide (1.7 x 10(-4)-8.5 x 10(-3) M). High concentrations (greater than or equal to 10(-3) M) of diazoxide, a drug that opens ATP-K channels, dramatically constricted the pulmonary vasculature and this effect was also reversed by tolbutamide. The opening of ATP-K channels may therefore underlie hypoxic pulmonary vasoconstriction. PMID- 2594947 TI - Infections in a renal unit. AB - Five hundred and thirty-three patients in the Oxford renal unit were reviewed to determine the incidence of infection in one calendar year. There were 310 patients who received dialysis, 53 with acute renal failure and 211 with chronic renal disease. Renal transplant patients were not included in the study. Apart from infections related to dialysis access, patients on maintenance haemodialysis or continuous ambulatory peritoneal dialysis developed few serious infections unless they had another disease causing suppression of immune function. A total of 97 urinary tract infections were seen; in patients with chronic renal disease not receiving dialysis the incidence of urinary tract infection was significantly associated with increasing uraemia, with diabetes, and with treatment with azathioprine or cyclophosphamide. In patients with acute renal failure, Gram negative septicaemia and fungal infections were important causes of morbidity and mortality, but cardiovascular disease caused 42 per cent of the deaths unlike results from other series where sepsis has been by far the commonest cause of death. PMID- 2594948 TI - Idiopathic hypoparathyroidism in black South Africans. AB - The spectrum of idiopathic hypoparathyroidism in black South Africans is described. Twelve patients were seen over a seven-year period. Major presenting features were tetany in 11, epilepsy in four, congestive cardiac failure in three, cataracts in four, neuropsychiatric disease in two, and basal ganglia calcification in four. Hypocalcaemia and hyperphosphataemia were apparent in all subjects at presentation. Parathyroid hormone levels were absent or inappropriately low in all. Important features highlighted were the long duration of symptoms before diagnosis, the suppression of tetany by treatment with diphenylhydantoin, the association of idiopathic hypoparathyroidism and epilepsy in adults, and the occurrence of reversible cardiac muscle dysfunction. PMID- 2594949 TI - Comparison of the prevalence and associated features of abnormal albumin excretion in insulin-dependent and non-insulin-dependent diabetes. AB - Overnight albumin excretion rates were measured in 940 diabetic patients, 416 with insulin dependent and 524 with non-insulin dependent diabetes, and in 106 healthy volunteers. A significantly higher number of non-insulin dependent diabetic patients had abnormal albumin excretion compared with the insulin dependent group (X2 = 15.2, p less than 0.002). Ten per cent of non-insulin dependent and 7 per cent of insulin-dependent diabetic patients had albumin excretion rates in the range 30-150 micrograms/min and thus were at risk of the cardiovascular and renal complications of diabetes. Six per cent of non-insulin dependent and 5 per cent of insulin-dependent diabetic patients had albumin excretion rates above 150 micrograms/min and thus were entering the phase of clinical diabetic nephropathy. Multivariate analysis revealed that male sex and retinopathy in insulin-dependent diabetes, and systolic blood pressure and retinopathy and peripheral vascular disease in non-insulin-dependent diabetes, were significantly related to albumin excretion. Only one patient with insulin dependent diabetes of less than 5 years known duration had an albumin excretion rate in the range 30-150 micrograms/min, whereas such an excretion rate indicating patients at risk was observed at all durations of non-insulin dependent diabetes. It is possible that during the long silent phase of non insulin-dependent diabetes, before diagnosis, significant renal damage occurred. PMID- 2594950 TI - The impact of an endoscopic laser service on gastroenterological practice. AB - During the 18 months following the introduction of a neodymium yttrium aluminium garnet laser in Newcastle upon Tyne 48 patients were treated, 23 for haemorrhage from peptic ulcers or vascular anomalies of the gut and 25 for palliation of inoperable tumours of the oesophagus, stomach and rectum. The treatment was tolerated well and was effective both for the arrest of haemorrhage and relief of dysphagia. Laser treatment has now entered the realms of routine clinical practice but its high cost and the operator expertise required suggest that its availability should be limited to designated centres. PMID- 2594951 TI - Zinc in the elderly. AB - Zinc levels in plasma and leucocytes of elderly patients with and without cutaneous ulcers and in hospital were compared with those of a group of healthy elderly living at home and of a younger group. The groups in hospital had lower levels of plasma and leucocyte zinc than the control groups, but these were not associated with cutaneous ulcers. The zinc intake of the patients in hospital was well below the recommended daily allowance. Tissue zinc levels were found to be low in elderly patients in hospital, probably due to poor intake, but their contribution to the formation of skin ulcers was unproven. PMID- 2594952 TI - Poikilothermia in a 68-year-old female. A risk factor for accidental hypothermia, or hyperthermia. AB - A 68-year-old woman presented in wintertime in a cold climate with ataxia and numbness in her legs and was found to be profoundly hypothermic in hospital. No endocrine or neurological cause for hypothermia could be distinguished. Physiological investigation, including a sympathetic release test, exposure to gradually increasing environmental temperatures and prolonged exposure to a high temperature suggested she was at that time regulating her core temperature around a set value which was several degrees lower than normal. Metabolic rate was 42 per cent below the value predicted from standard tables. Further measurements over a one-month period in a warm climate suggested a poikilothermic temperature control mechanism, with a possible risk of environmental hyperthermia. No pathological basis for this disorder has yet been identified, but it is suggested that a small localized hypothalamic vascular event has occurred. PMID- 2594953 TI - Characterization of the anaemia of chronic renal failure and the mode of its correction by a preparation of human erythropoietin (r-HuEPO). An investigation of the pharmacokinetics of intravenous erythropoietin and its effects on erythrokinetics. AB - Studies were directed to characterization of the anaemia of renal failure of 11 patients on haemodialysis and determination of the way in which it is corrected by human erythropoietin derived from recombinant DNA expressed in Chinese hamster ovary cells (r-HuEPO) administered intravenously. Erythrokinetics before treatment showed that total red cell mass was below normal and that both erythron transferrin uptake and red cell survival were modestly reduced; treatment increased both total red cell mass and erythron transferrin uptake but did not change red cell survival in previously untransfused patients. When BFU-e and CFU e from patient bone marrow were cultured in autologous serum we found no evidence for inhibitors of erythroid progenitor maturation in patient serum compared with normal. Erythroid expansion in response to r-HuEPO was not limited by the availability of iron, iron requirements for new red cell formation being met from stores (if adequate) or from oral iron supplements. In pharmacokinetic studies the plasma clearance of r-HuEPO could be expressed by a three-parameter exponential curve with T1/2 range of 2.3 to 7.3 h. T1/2 after the first dose of r HuEPO was not significantly different from that after 14 to 54 weeks treatment when the erythron had expanded to a new steady state. Erythron transferrin uptake before treatment was related to endogenous production of erythropoietin estimated from the plasma clearance of the first dose of r-HuEPO administered intravenously. This finding suggested that the availability of erythropoietin was the main factor limiting expansion of the erythron. This conclusion was supported by the continuity of the relationship during the response to treatment. PMID- 2594954 TI - Candidiasis-endocrinopathy syndrome with progressive myopathy. AB - A women suffering from the candidiasis-endocrinopathy syndrome, developed severe myopathy in her fourth decade and died from it at the age of 37 years. Associated conditions were hypoparathyroidism, vitiligo, chronic mucocutaneous candidiasis, short stature, intellectual disability, ovarian failure and alopecia totalis. Muscle biopsy findings were non-specific with focal atrophy of type 2 fibres. Serum immunoglobulin levels were normal. The only demonstrable abnormalities of her immune system were impaired T-cell function and antibody production by B cells (detectable to smooth muscle, mitochondria and gastric parietal cells). The T-cell abnormality may have been part of a more generalized cell defect, resulting from an unidentified genetic abnormality, whilst the circulating antibodies could have been a response to tissue damage. There was no convincing evidence of primary autoimmune damage. PMID- 2594955 TI - Hypopituitarism following external radiotherapy for pituitary tumours in adults. AB - The development of anterior pituitary hormone deficiencies has been studied in a group of 165 patients who underwent external radiotherapy for tumours of the pituitary or closely related anatomical sites, and who have been observed for up to 10 years. One hundred and forty had undergone pituitary surgery before radiotherapy. All patients received external radiotherapy by a three-field technique, giving 3750-4250 cGy in 15 or 16 fractions over 20-22 days. A combined test of anterior pituitary function using insulin hypoglycaemia or glucagon stimulation in conjunction with thyrotrophin and gonadotrophin releasing hormone tests and basal estimations of prolactin, thyroid hormones and testosterone or oestradiol was performed before radiotherapy. This was repeated six and 12 months later and subsequently annually. Before radiotherapy, 18 per cent of patients had normal growth hormone secretion, 21 per cent had normal gonadotrophin secretion, 57 per cent had normal corticotrophin reserve and 80 per cent had normal thyrotrophin secretion. Life table analysis demonstrated increasing incidences of all anterior pituitary hormone deficiencies with time: by five years all patients were growth hormone deficient, 91 per cent were gonadotrophin deficient, 77 per cent were corticotrophin deficient and 42 per cent were thyrotrophin deficient. At eight years, respective incidences of deficiencies were 100, 96, 84 and 49 per cent. Radiation-induced hyperprolactinaemia was seen in 73 patients; mean serum prolactin concentration rose from 227 +/- 11 mU/l to a peak of 369 +/- 60 mU/l at two years and subsequently declined towards the basal value. The primary diagnosis, patient age, sex, irradiated tissue volume and previous surgery were examined as variables that might influence the rate of development of anterior pituitary hormone deficiencies, but none of these factors had a significant effect. The radiation induced hyperprolactinaemia was however more marked in female patients. Although anterior pituitary hormone deficiencies most commonly developed in the order growth hormone, gonadotrophin, corticotrophin, thyrotrophin (61 per cent of patients), other sequences were evident. Most notably corticotrophin deficiency occurred before gonadotrophin deficiency. There is a high incidence of anterior pituitary hormone deficiencies in patients treated surgically for pituitary tumours and the incidence increases after external radiotherapy. Deficiencies may occur in an unpredictable sequence and endocrine testing is recommended on an annual basis. PMID- 2594956 TI - Iron status of hospitalized and housebound elderly people: dietary intake, metabolic balances, haematological and biochemical indices. AB - The iron status of housebound and hospitalized elderly people was studied by duplicate diet analysis, metabolic balance, biochemical and haematological investigations. Evidence of biochemical iron deficiency in the hospital group was accompanied by low dietary intake and negative metabolic balance. Metabolic equilibrium in the housebound group was seen with intakes similar to those found in healthy elderly though biochemical measures suggested a borderline iron deficient state. PMID- 2594957 TI - Use of zidovudine. PMID- 2594958 TI - Strategies for preventing hepatitis B. PMID- 2594959 TI - Nocturnal asthma. PMID- 2594960 TI - Extrapyramidal reactions to metoclopramide and prochlorperazine. AB - We have investigated prospectively the incidence of extrapyramidal events amongst patients receiving 'first' prescriptions for metoclopramide (n = 2557) and prochlorperazine (n = 2811) from general practitioners in the Northern Region using community pharmacists to capture prescriptions. There were 12 reports of acute dystonic-dyskinetic events following metoclopramide and the incidence of this reaction was significantly greater in those under 30 years than in those 30 years and over. Following prochlorperazine there were eight reports of Parkinsonism in patients whose ages were known; seven were over 60 years. The incidence in those over 60 years was significantly higher than in those less than 60 years. PMID- 2594961 TI - Antenatal screening for hepatitis B is medically and economically effective in the prevention of vertical transmission: three years experience in a London hospital. AB - We describe our experience over a three-year period in the detection of antenatal patients with hepatitis B virus (HBV) carriage, and the successful prevention of vertical transmission in the infants of HBsAg-positive women. Nine of the 26 infants born to HBsAg-positive mothers were considered to be at high risk of infection. Eight of these nine remained HBsAg-negative after passive or passive/active immunization. The majority of infants tested had anti-HBs antibody titres above 10 i.u./l from the first month. In comparison with the cost of caring for patients with chronic hepatitis B infection and decompensated cirrhosis, non-selective testing of pregnant women for HBsAg is found to be cost effective. PMID- 2594962 TI - Pulmonary brucellosis. AB - Pulmonary abnormalities in brucellosis are rare. We report on nine cases (five adults and four children) with pulmonary brucellosis. All presented with fever, cough and mucopurulent sputum, and most had abnormal signs in the chest. Radiography of the chest showed pneumonic patches or consolidation in five patients, pleural effusion in three, granuloma of the lung in one and a picture of interstitial pneumonitis in one. All the patients had a brucella agglutination titre of 1:320 or more, and an elevated titre in the brucella-specific enzyme linked immunosorbent assay of IgM, IgG and IgA. Blood cultures grew Brucella melitensis in six patients while the pleural fluid aspirate grew the same organism in two of three patients. Treatment with oral oxytetracycline, doxycycline, rifampicin, trimethoprim-sulfamethoxazole alone, in combination with each other or together with intramuscular streptomycin was successful in all patients. All our patients recovered and none relapsed. PMID- 2594963 TI - Idiopathic familial atrial cardiomyopathy with diffuse conduction block. AB - Isolated atrial cardiomyopathy is rare and familial idiopathic atrial cardiomyopathy has only been described once. We describe a case characterized by severely reduced atrial contractile function, intermittent atrial electrical standstill, diffuse interatrial, intraventricular and atrioventricular block, complicated by systemic embolism. Whilst this condition is undoubtedly rare, other cases may be being mistaken for simple sinoatrial disease. PMID- 2594964 TI - Quality of life and survival following intensive medical care. AB - The relation between quality of life before admission and the outcome of admissions to the intensive care unit (ICU) was studied prospectively among 126 patients in a community hospital with a predominantly geriatric patient population. Fifty-four per cent of our patients were older than 65 years and 66 per cent suffered from chronic ill health. Their mean APACHE score was 18 +/- 8 (mean +/- SD). Quality of life was assessed by the Karnofsky index of physical performance; the linear analogue self assessment (LASA) score; sleep index; level of employment; sexual activity; housing status. Thirty-seven per cent of the patients died in ICU and another 10 per cent in hospital. The one year survival of the entire group was 37 per cent. Survival rates were significantly higher in patients with a Karnofsky index of 6 or more, LASA score of 55 or more, in employment, and with sleep index of 2 or more (p less than 0.05). The 12-month survival among patients with four favourable indicators was 59 per cent, with two or three favourable indicators 36 per cent (p less than 0.05), and in patients with no favourable indicators of quality of life or only one 17 per cent (p less than 0.001). Quality of life in patients who survived longer than six months after ICU care was high (Karnofsky index 7.9 +/- 2.0; LASA score 71 +/- 20 (mean +/- SD) and unimpaired when compared with their ratings before admission to the unit. These findings indicate that quality of life before admission is an important predictor of survival and that a high proportion of critically-ill subjects whose quality of life was relatively good before the episode requiring admission will be long-term survivors whose quality of life is comparable to that preceding critical care. PMID- 2594965 TI - Probabilistic approach to obtain hit-size effectiveness functions which relate microdosimetry and radiobiology. AB - A probabilistic approach has been developed to relate microdosimetry, biological effects, and radiation quality. It is used to derive, and subsequently apply, microdosimetry-based cellular response functions for different biological end points of relevance for radiological protection. The approach makes use of measurable microdosimetry spectra and avoids assumptions concerning the course of mechanisms of radiation action. Instead, it postulates a response function that is, and behaves like, the cumulative probability that a subcellular target structure will respond to a specific target-averaged ionization density. Statistical distributions are applied and their parameters are evaluated to characterize the randomness involved in the localization of sensitive sites and in the reactivity of the whole sensitive structure. The resulting response functions can be used for prediction of the effects of low-level radiation. Such predictions for some selected effects of a stochastic nature (mutagenesis, chromosome abnormalities, etc.) are presented as relative biological effectiveness values based on low doses of radiations with a wide range of linear energy transfer and compared with various quality factor specifications. Cellular response relationships, termed hit-size effectiveness functions, can also be applied directly in radiation protection metrology by incorporating them into the software used to process the readings of microdosimetric spectrometers. The derivation of the functions, rather than their uses in radiation protection, is the principal subject of this report. PMID- 2594966 TI - Increased radioresistance of tumor cells exposed to metallothionein-inducing agents. AB - In this study, we have determined the radiosensitivity parameters of cells exposed in vitro to metallothionein-inducing agents. Three well-characterized tumor cell lines were chosen for investigation: HeLa, B16, and WHFIB. We have shown that exposure of cells in vitro to a heavy metal (cadmium), followed by irradiation, enhances cell survival for two out of three cell lines studied. As measured by the mean inactivation dose, the radioresistance increases by a factor of 1.6 for HeLa cells, 1.4 for WHFIB, and a negligible factor for B16 cells. An additional effect was noted when different classes of metallothionein inducers (such as serum factors, cadmium, and dexamethasone) were allowed to act together. Also, we found that the increase in radioresistance exhibits a peak at exposure times of approximately 10 h; longer exposure to inducing agents results in a reduction in radioresistance. PMID- 2594967 TI - Radiation-induced neoplastic transformation of C3H10T1/2 cells is suppressed by ascorbic acid. AB - X-ray induced transformation of C3H10T1/2 cells was suppressed in a concentration dependent manner by administration of ascorbic acid after irradiation (0.1-20 micrograms/ml for the first week) in the culture medium. The dose-response curve was shifted about 60% downward and was slightly steeper in the presence of ascorbic acid (5 micrograms/ml for the first week) than in its absence. The 1 week treatment procedure revealed that cells initiated by radiation remained susceptible to ascorbic acid until the time of morphological phenotype expression. The neoplastically transformed phenotype expressed after incubation for 8 weeks could no longer be suppressed by ascorbic acid even after culture transfer. Similarly, the neoplastically transformed phenotype suppressed for 8 weeks by ascorbic acid treatment was not subsequently expressed in the absence of ascorbic acid. On the basis of the oxygen-detoxifying nature of ascorbic acid, we postulated that expression of the neoplastically transformed phenotype is promoted by reactive oxygen species and peroxy radicals generated in cells during the whole assay period. The data may be useful as a guide for chemopreventive efforts against radiation carcinogenesis. PMID- 2594968 TI - Neoplastic cell transformation by heavy ions. AB - We have studied the induction of morphological transformation by heavy ions. Golden hamster embryo cells were irradiated with 95 MeV 14N ions (530 keV/microns), 22 MeV 4He ions (36 keV/microns), and 22 MeV 4He ions with a 100 microns Al absorber (77 keV/microns) which were generated by a cyclotron at the Institute of Physical and Chemical Research in Japan. Colonies were considered to contain neoplastically transformed cells when the cells were densely stacked and made a crisscross pattern. It was shown that the induction of transformation was much more effective with 14N and 4He ions than with gamma or X rays. The relative biological effectiveness (RBE) relative to 60Co gamma rays was 3.3 for 14N ions, 2.4 for 4He ions, and 3.3 for 4He ions with a 100-microns Al absorber. The relationship between RBE and linear energy transfer was qualitatively similar for both cell death and transformation. PMID- 2594970 TI - The induction of chromosome damage in CHO cells by beryllium and radiation given alone and in combination. AB - Studies were conducted to determine the effects of BeSO4 or X rays, alone and in combination, on cell cycle kinetics, cell killing, and the production of chromosome aberrations in Chinese hamster ovary (CHO) cells. The concentration of BeSO4 required to kill 50% of CHO cells exposed to BeSO4 for 20 h was determined to be 1.1 mM with 95% confidence intervals of 0.72 to 1.8 mM. During the last 2 h of the 20-h beryllium treatment (0.2 and 1.0 mM), cells were exposed to 0.0, 1.0, or 2.0 Gy of X rays. Exposure to either BeSO4 or X rays produced a change in cell cycle kinetics which resulted in an accumulation of cells in the G2/M stage of the cell cycle. However, combined exposure to both agents resulted in a block similar to that observed following exposure to X rays only. The background level of chromosome damage was 0.05 +/- 0.015 aberrations/cell in the CHO cells. Seven hours after the end of exposure to 0.2 and 1.0 mM beryllium, 0.03 +/- 0.003 and 0.09 +/- 0.02 aberrations/cell, respectively, were observed. The data for chromosome aberrations following X-ray exposure were fitted to a linear model with a coefficient of 0.14 +/- 0.01 aberrations/cell/Gy. When beryllium was combined with the X-ray exposure the interactive response was predicted by a multiplicative model and was significantly higher (P less than 0.05) than predicted by an additive model. The influence of time after radiation exposure on the interaction between beryllium and X rays was also determined. No interaction between beryllium and X-ray exposure in the induction of chromosome-type aberrations (P greater than 0.05) was detected. The frequency of chromatid-type exchanges and total aberrations was significantly higher (P less than 0.05) in the radiation plus beryllium-exposed cells when compared to cells exposed to X rays only, at both 9 and 12 h after X-ray exposure. These data suggest that the multiplicative interaction may be limited to cells in the S and G2 stages of the cell cycle. PMID- 2594969 TI - Correlations between 31P-NMR spectroscopy and tissue O2 tension measurements in a murine fibrosarcoma. AB - Size-dependent changes in therapeutically relevant and interrelated metabolic parameters of a murine fibrosarcoma (FSaII) were investigated in vivo using conscious (unanesthetized) animals and tumor sizes less than or equal to 2% of body weight. Tumor pH and bioenergetics were evaluated by 31P nuclear magnetic resonance spectroscopy (31P-MRS), and tumor tissue oxygen tension (pO2) distribution was examined using O2-sensitive needle electrodes. During growth FSaII tumors showed a progressive loss of phosphocreatine (PCr) and nucleoside triphosphate (NTP) with increasing inorganic phosphate (Pi) and phosphomonoester (PME) signals. Ratios for PCr/Pi, PME/Pi, NTP/Pi, and phosphodiester/inorganic phosphate (PDE/Pi) as well as pH determined by 31P-NMR (pHNMR) and the mean tissue pO2 progressively declined as the tumors increased in size. The only relevant ratio increasing with tumor growth was PME/NTP. When the mean tissue pO2 value was plotted against pHNMR, NTP/Pi, PCr/Pi, PME/Pi, and PDE/Pi for tumor groups of similar mean volumes, a highly significant positive correlation was observed. There was a negative correlation between mean tumor tissue pO2 values and PME/NTP. From these results we concluded that 31P-MRS can detect changes in tumor bioenergetics brought about by changes in tumor oxygenation. Furthermore, the close correlation between oxygenation and energy status suggests that the microcirculation in FSaII tumors yields an O2-limited energy metabolism. Finally, a correlation between the proportion of pO2 readings between 0 and 2.5 mmHg and the radiobiologically hypoxic cell fraction in FSaII tumors was observed. The latter finding might be of particular importance for radiation therapy. PMID- 2594971 TI - Intraoperative radiation therapy-induced sarcomas in dogs. AB - In a canine model the tolerance of normal and surgically manipulated tissue to intraoperative radiotherapy (IORT) was investigated to provide guidelines for the clinical use of IORT in human cancer patients. A dose of 20 Gy IORT, with or without external beam radiotherapy, was generally well tolerated without significant increased treatment morbidity. Higher doses of IORT (over 30 Gy) have produced radiation-induced sarcomas in some animals followed over a long period. Therefore IORT should be used only in human cancer patients in well controlled studies, in which complications are well documented, and the possibility of radiation-induced malignancies in long-term survival should be considered. PMID- 2594972 TI - Thyroid neoplasia following low-dose radiation in childhood. AB - The thyroid gland is highly sensitive to the carcinogenic effects of ionizing radiation. Previously, we reported a significant increase of thyroid cancer and adenomas among 10,834 persons in Israel who received radiotherapy to the scalp for ringworm. These findings have now been extended with further follow-up and revised dosimetry. Overall, 98 thyroid tumors were identified among the exposed and 57 among 10,834 nonexposed matched population and 5392 sibling comparison subjects. An estimated thyroid dose of 9 cGy was linked to a fourfold (95% Cl = 2.3-7.9) increase of malignant tumors and a twofold (95% Cl = 1.3-3.0) increase of benign tumors. The dose-response relationship was consistent with linearity. Age was an important modifier of risk with those exposed under 5 years being significantly more prone to develop thyroid tumors than older children. The pattern of radiation risk over time could be described on the basis of a constant multiplication of the background rate, and an absolute risk model was not compatible with the observed data. Overall, the excess relative risk per cGy for thyroid cancer development after childhood exposure is estimated as 0.3, and the absolute excess risk as 13 per 10(6) PY-cGy. For benign tumors the estimated excess relative risk was 0.1 per cGy and the absolute risk was 15 per 10(6) PY cGy. PMID- 2594974 TI - Identification of irradiated pepper with the level of hydrogen gas as a probe. AB - A novel method to detect whether or not a particular pepper has been irradiated has been developed which is based on the fact that H2 is formed in organic substances irradiated with ionizing radiation. Following gamma irradiation, black and white peppers were ground to powder in a gastight ceramic mill. By gas chromatographic analysis of the gas in the mill, we observed that H2 had been released from the irradiated pepper grains. Curves plotting the H2 content vs storage time at storage temperatures of 7, 22, and 30 degrees C showed that the higher the temperatures, the smaller the H2 content, and that identification of irradiated pepper was possible for 2-4 months after 10 kGy irradiation. PMID- 2594973 TI - Formation and repair of DNA-protein crosslinks in newly replicated DNA. AB - The production and removal of gamma-radiation-induced DNA-protein crosslinks (DPC) in nuclear matrix-associated newly replicated DNA were examined, as well as the relationship of DPC to DNA replication. In unirradiated, exponentially growing Chinese hamster V79 cells, DNA pulse labeled with [3H]thymidine was observed to be bound preferentially to protein. The pulse-labeled DNA subsequently became dissociated from protein. After a 30- to 60-min chase period, the level of labeled DNA in DPC was reduced to the same level as for bulk DNA. The radiation dose response for the formation of DPC was similar in newly replicated DNA that had been chased for various times and in mature chromatin DNA. Labeled DNA, in the DPC formed after 60 Gy, was rapidly removed from protein during the postirradiation incubation period. However, no recovery of DNA synthesis was observed, even after the majority of DPC were released. Thus either DPC are not the sole cause of the inhibition of DNA synthesis or their removal is not sufficient for DNA synthesis to resume. PMID- 2594975 TI - Nurse charges "unfair labor practice". PMID- 2594976 TI - Nursing Board's "Position Paper" held "rulemaking". Case in point: Ohio Nurses Assn. v. State Bd. of Nursing (540 N.E. 2d 1354--OH (1989)). PMID- 2594978 TI - 6 1/2 inch scissor clamp left in patient. Case in point: Fox v. Oklahoma Memorial Hosp. (774 P. 2d 459--OK (1989)). PMID- 2594977 TI - Legal case briefs for nurses. N.Y.: cyst removal: illegal practice issue; D.C.: nurse advises "Sweat it out": death results. PMID- 2594979 TI - Can your hospital sue you for malpractice? PMID- 2594980 TI - Nurse gives sandwich to patient in labor. Case in point: Osborne v. Annie Penn Mem. Hosp. (381 S.E.2d 794--NC (1989)). PMID- 2594982 TI - Death from amniotic embolism: "lost chance" doctrine. Case in point: Falcon v. Memorial Hospital (443 N.W. 2d 431--MI (1989)). PMID- 2594981 TI - Legal case briefs for nurses. AL.: electrode burns: nurse-expert testimony; IL.: "patient dumping": violation of federal law. PMID- 2594983 TI - [Rice genomic DNA]. PMID- 2594984 TI - [Rice mitochondrial genome]. PMID- 2594985 TI - [Rice chloroplast genome]. PMID- 2594987 TI - [Tumor necrosis factor and AIDS--the mechanism of development of AIDS]. PMID- 2594986 TI - [Gene transfer in rice]. PMID- 2594989 TI - [Enzyme deficiency in the lymphocytes of tobacco smokers]. AB - In the peripheral blood lymphocytes of 85 men aged 18 to 42 years, smoking cigarettes by 2 to 25 years, the intracellular enzymes activity having varying localization, has been determined by the use of semiquantitative histochemical methods. The lymphocytes from subjects smoking not more than 10 years the increased activity of acid phosphatase, leucyl aminopeptidase, and lactic dehydrogenase as well as decreased activity of N-acetyl-beta-D-glucosaminidase has been stated. In contrast, in subjects smoking more than 10 years the intracellular activity of acid phosphatase, beta-glucuronidase, N-acetyl-beta-D glucosaminidase and lactic dehydrogenase in lymphocytes has been diminished. Above enzymatic deficiencies could represent the biochemical basis of functional alterations of lymphocytes from smokers observed by numerous authors. PMID- 2594988 TI - [Disorders of lipid and lipoprotein metabolism in patients with chronic lymphocytic leukemia. I. Preliminary evaluation of lipemia and HDL fractions in various stages of the disease]. AB - The study comprised 128 patients with chronic lymphocytic leukemia (CLL) aged 65.7 +/- 8 years, 59 women and 69 men. Among the patients studied 70 were treated and 58 yet not underwent therapy. The Rai classification of patients with CLL has been used. The control group consisted of 68 subjects aged 56.8 +/- 14 years, 35 women and 33 men, showing no diseases affecting the blood lipid disturbances. The following determinations have been performed in the blood serum: apo B, CH, TG, PL, and CH or PL in the isolated HDL fraction; LDL-CH ratio has also been calculated. In patients with CLL the total CH concentration has been noted which advanced parallel to the disease progress. It resulted first of all from the decrease in LDL-CH (p less than 0.05). Similar alterations have been noted so far as apo B is concerned. It has been demonstrated that the decrease in HDL-CH (p less than 0.05) is also dependent on the disease stage. The simultaneously increasing index HDL-PL/HDL-CH indicate on changes within the HDL2 and HDL3 subfractions suggesting a deficiency of the HDL2 subfraction. The total lipemia and the lipoprotein fraction alterations observed make the diagnostic value of the atherosclerotic threat in patients with CLL doubtful with the use of that parameters. PMID- 2594991 TI - [Usefulness of determining serum levels of prolactin in women with menstruation disorders]. AB - In 173 women with oligomenorrhea or amenorrhea, serum level of prolactin (PRL) was determined by radioimmunoassay method. In 22 cases (12.7%) the concentration of PRL was above 15 ng/ml. From the above women in 9 cases (5.2%) of all examined patients pituitary microadenoma was diagnosed. In 1 patient with pituitary microadenoma, coexisting partially empty sella was diagnosed. The mean basal PRL concentration in women with menstruation disturbances without hyperprolactinemia (group I) was found to be 7.1 +/- 3.1 ng/ml while the women with hyperprolactinemia without pituitary microadenoma (group II) was 32.9 +/- 5.8 ng/ml. In women with diagnosed pituitary microadenoma (group III) PRL concentration was 131.8 +/- 47.7 ng/ml. The group II and III demonstrated statistically significant increase of serum prolactin level in comparison to group I. Moreover in comparison with group I, statistically significant reduction of serum level of FSH, LH and estradiol 17 beta was confirmed in group with pituitary microadenoma. In group II significant decrease of serum concentration of LH and estradiol 17 beta was stated as well as lack of significant difference in serum level of FSH, in comparison to group I. PMID- 2594990 TI - [Effect of hemodialysate and its peptide fractions on stromal cells and heme synthesis in bone marrow culture and the activity of selected enzymes and GSH level of human erythrocytes. I. Effect on LDH activity in healthy persons and patients with terminal renal failure]. AB - The purpose of the study was in evaluation of the effect of hemodialysate and its 3 peptide fractions on the lactic dehydrogenase (LDH, E.C.1.1.1.28) activity in erythrocytes in patients treated by repeated hemodialyses due to the terminal renal failure and in healthy subjects. It has been demonstrated that erythrocytes from hemodialysed patients show significantly diminished activity of LDH if compare with that in the healthy subjects. Activity of that enzyme in erythrocytes from healthy subjects after 3 hours lasting incubation with hemodialysate having concentration 675 and 450 micrograms/ml calculated against the protein content has significantly been lowered. Similarly, peptide fraction III in the incubative concentration 270 and 190 micrograms/ml induced significant inhibition of the enzyme activity. Both hemodialysate and its peptide fractions do not influenced the LDH activity in erythrocytes from patients treated by repeated hemodialyses. PMID- 2594992 TI - [The role of the physician in expert testimony leading to an arrest]. AB - The authors have offered several problems related to a topic of medical professional activities of physicians being in contact with the administration of justice. There are presented opinions based on existent regulations and experiences associated with juridical expert activities of the authors. These opinions are about two problems that, according to obtained data, are made of controversies which stand between first-aid or ambulance doctors and law officers. The first problem deals with differences of opinion on obligations of physicians to examine drunk patients and to meet the requirements to put them into a sober room or--if there are any for a temporary stay into a prison. There has been also stated an opinion that this activity of physicians is included in a normal range of their professional duties. The second matter is concerned with the correctness of physicians' proceedings dealing with individuals arrested by militia and giving medical evidences that faces a problem whether stay in prison can or cannot constitute a threat for their life or health. It's been also founded that--in those cases--a physician has to be called a medicolegal opinion. The professional obligations of physicians still don't include this function and therefore it has to be granted separately. PMID- 2594993 TI - [Tumor necrosis factor (TNF)--its biochemical characteristics and biological properties]. PMID- 2594995 TI - [The role of general medicine in present-day science and its significance for medical practice]. PMID- 2594994 TI - [The possibility of using an intramedullary Y nail in failure of the surgical treatment of trochanteric fractures of the femur using an angular McLaughlin nail]. PMID- 2594997 TI - [Effect of hemodialysate and its peptide fractions on stromal cells and heme synthesis in bone marrow culture and the activity of selected enzymes and GSH level in human erythrocytes. I. Effect on human bone marrow stromal cells in vitro]. AB - Hemodialysate or its three peptide fractions added to the culture of human bone stromal cells in vitro in concentration equal to 5 micrograms/ml of medium calculated against the protein content showed varying toxicity extent as expressed by shortening of cell survival time. Fraction III and hemodialysate showed the most toxic effect and shortened the cell survival time by three 24 hour periods in comparison to the control culture. Fraction III contained peptides having molecular weights in the range 1 to 5 kda that is was rich in compounds of the so-called middle molecular weights. Both hemodialysate and peptide fractions altered in the culture the participation of stromal cells reflected by diminishing the number of fibroblasts or adipocytes and an increase in the macrophage count. Above alterations speak in favor of concept that both hemodialysate and peptide fractions contain the macrophage proliferation stimulatory factor(s). PMID- 2594996 TI - [Vitamins A and E and vitamin A-binding proteins in the blood serum of patients with esophageal cancer]. AB - The mean values of the vitamin A and the beta-carotene in the blood serum of patients with oesophageal cancer are lower than that in patients with nonmalignant oesophagus diseases and those with diseases other than malignancies and oesophageal diseases. The total protein and the albumin concentration in the blood sera did not differ when the above three groups of patients were compared. The concentration of vitamin E in the blood serum was similar in all three groups studied. The concentration of vitamin A in the group of patients with oesophageal cancer showed a marked correlation with the concentration of the vitamin A binding proteins in the blood serum. PMID- 2594998 TI - [Effect of hemodialysate and its peptide fragments on stromal cells and heme synthesis in bone marrow culture and the activity of selected enzymes and GSH in human erythrocytes. II. Effect on heme synthesis by the erythroid cells of the human bone marrow in vitro]. AB - Effect hemodialysate or its three peptide fractions on the heme synthesis in in vitro cultured human bone marrow erythroid cells has been studied using the 59Fe incorporation method. Heme has been extracted from human bone marrow erythroblasts. Under the hemodialysate (concentrations equal to 350 and 200 micrograms/ml) and the fraction II (concentrations equal to 14 micrograms/ml of medium calculated against the protein content) effect the 59Fe incorporation (cpm) 10(6) of nucleated marrow cells) has statistically been elevated. Hemodialysate showing capability to stimulate the heme synthesis contained peptides having molecular weights in the range of 5 to 45 kda; the molecular weights of fraction II components remained in the range of 5 to 15 kda. Since other hemodialysate peptide fractions showed no stimulatory effect on the 59Fe incorporation to heme it could be suggested that the active substance has molecular weight corresponding to 5 to 15 kda. Moreover, the substances correspond not to erythropoietin which molecular weight remains in the range of 34 to 40 kda. On the whole, it has been demonstrated that the blood factor stimulating heme synthesis reaches the dialysate. PMID- 2594999 TI - [Idiopathic nephrotic syndrome. II. Humoral disorders and complications]. PMID- 2595000 TI - [Effect of drug therapy of hyperthyroidism on the electrophysiological parameters of the heart]. AB - Investigations of heart automatism have been performed in 10 patients with hyperthyreosis prior and after the euthyreosis obtaining with the methizol therapy. The control group consisted of 34 healthy volunteers. The electrophysiologic parameters of heart were determined by the transoesophageal stimulation of atrium using the method of single impulse and rapid stimulation. Instantly after obtaining the remission the normorhytmia has been observed; moreover, the significant elongation of the effective time of atium refraction and of the border interval, has been noted; the last two parameter were shorter than in the control group. The normalization of the border atrioventricular conduction and the sinusal rhythmus return as well as appearance in half of patients treated of latent block of intracardial conductivity has also been stated. According to the authors' opinion the early period after the obtaining of euthyreosis by the use of methizol is characterized by cardiological risk. PMID- 2595001 TI - [Study of magnesium levels in the blood and urine in acute pancreatitis]. AB - The magnesium concentration in the body fluids has been determined in 39 patients with mild acute pancreatitis having no ethanol etiology. The results obtained have been compared with that in 30 healthy blood donors. The normal magnesium concentration in the blood plasma has been stated during the first day of treatment in the patients studied. During the treatment the magnesium concentration in the blood plasma showed only minor fluctuations and increased slightly only in the fifth day of the disease. The magnesium concentration in erythrocytes of the patients studied was slightly, not significantly, elevated and did not change during the subsequent days of treatment. The magnesium excretion in the urine increased during the fifth days of the disease. PMID- 2595002 TI - [Serum lipids and lipoproteins in patients with cerebrovascular disorders]. AB - In 150 patients with cerebral insult and in 153 subjects of the control group the studies have been performed with an aim to establish the biochemical evaluation of the arteriosclerotic threat. The cholesterol, phospholipid, triglyceride and apo B concentration in the serum as well as quantitative evaluation of the HDL and LDL fractions were involved. The sex-related differences have been found so far as apo B and lipid serum components are concerned. The most characteristic alterations have been showed in the HDL fraction. In the all patients studied the significant decrease in the HDL-CH concentration as well as an increased HDL PL/HDL-CH index has been noted suggesting changes in the HDL subfraction leading to the diminished concentration of anti-atherogenic HDL2 fraction. PMID- 2595003 TI - [Effect of hemodialysate and its peptide fragments on stromal cells and heme synthesis in bone marrow culture and the activity of selected enzymes and GSH level in human erythrocytes. III. Effect on G-6-PD in erythrocytes of healthy persons and those with terminal renal failure]. AB - It has been found that erythrocytes of hemodialysed patients show significantly increased glucose-6-phosphate dehydrogenase (G-6-PD, E.C. 1.1.1.49) activity when compared with that in healthy subjects. Activity of that enzyme in erythrocytes from patients treated with hemodialyses incubated in 3 hours with hemodialysate (HD) or its peptide fractions (PF) showed no statistical difference when compared with controls. Similar effect of HD or PF on activity of the enzyme studied has been noted in erythrocytes from healthy subjects except fraction II having concentration equal to 14 micrograms/ml calculated against the protein content. This last fraction caused significant inhibition of the enzyme activity. PMID- 2595004 TI - [Should the kidneys be transplanted from cadavers or from living donors?]. PMID- 2595005 TI - [Medicine without physicians. Traditional image of physicians and the present-day world]. PMID- 2595006 TI - Marking effects in instrumental performance on DRH schedules. AB - Three experiments investigated the effect of presenting a brief stimulus after a response sequence on the rate of lever-pressing by rats on differential reinforcement of high rate (DRH) schedules. In Experiment 1 enhanced responding was produced by a visual stimulus presented during a 500-msec delay of reinforcement compared to a condition in which no stimulus was presented. In Experiment 2 rats responded on a multiple DRH DRH schedule in which the DRH contingency was reinforced on a 50% schedule in each component. Equivalent levels of responding occurred in the components when reinforcement was signalled in one component and when the signal was presented following the non-reinforced schedules in the other components. A further group of rats received the stimulus presented after non-reinforced schedules in one component but not at all in the other component; responding was enhanced in the former component relative to the latter component. In Experiment 3 brief stimuli presented after the completion of DRH components on a second-order VR (DRH) schedule elevated response rates irrespective of whether the signal was presented paired or unpaired with reinforcement. The present data support the view that a brief signal may serve to mark a response sequence in memory and facilitate instrumental performance. PMID- 2595007 TI - Attenuation of latent inhibition after compound pre-exposure: associative and perceptual explanations. AB - Three experiments used rats as subjects and the conditioned emotional response (CER) paradigm to examine the effect of pre-exposure to a compound stimulus on the extent of latent inhibition to an element of that compound. In Experiment 1a a group of rats exposed to a compound that comprised a tone and a click exhibited less latent inhibition to the tone than did a group that had received pre exposure to the tone in isolation. Experiment 1b showed that pre-exposure to the tone/click compound also resulted in an attenuation of latent inhibition to the click relative to a group that was pre-exposed to the click in isolation. Experiment 2 demonstrated that latent inhibition to the tone was left intact following pre-exposure to the tone in compound with a light. This pattern of results seems to be most plausibly explained in terms of the presence and absence of generalization decrement following compound pre-exposure. PMID- 2595008 TI - Resistance to extinction following habituation to behaviourally disruptive novel stimuli. AB - Three experiments tested the prediction, derived from generalized frustration theory (Amsel, 1972), that habituation to behaviourally disruptive stimuli increases resistance to extinction in the runway. In each experiment, rats received initial consistent reinforcement (CRF) training and then either continued CRF (Groups C), partial reinforcement (PRF) training (Groups P), or CRF accompanied by presentations of a novel tactile, tone, or obstacle stimulus (Groups D) in Experiments 1-3, respectively. PRF increased resistance to extinction whether non-reinforcement disrupted behaviour (Experiment 1) or not (Experiments 2 and 3). The tactile and obstacle stimuli very substantially disrupted behaviour, and the tone produced a modest disruption of behaviour. All subjects habituated to the disruptive effects of these stimuli, but Group D was not more resistant to extinction than Group C in any experiment. The results suggest that non-reinforcement has unique stimulus properties, a consequence of which is that habituation to other sources of disruptive stimulation does not promote responding to non-reinforcement in extinction. PMID- 2595009 TI - The recording of morbidity related to radiotherapy. AB - Radiation morbidity is as important as tumour control when determining the value of radiotherapy, but there is no internationally agreed system for the recording of morbidity. A scheme based upon the scoring of the elements which make up morbidity has been endorsed by a 2-day Workshop sponsored by the Medical Research Council and a system is now available for trial. PMID- 2595010 TI - In situ benign growth after radical radiation therapy of head and neck cancers- report of eight patients. AB - Eight patients who developed benign growth at the primary site after radical radiotherapy of head and neck cancers (two laryngeal cancers, six nasopharyngeal carcinoma, NPC) are reported. Most of the lesions appeared as spheral or nodular growth with few symptoms. All were properly diagnosed and treated, but two of them had been wrongly diagnosed and treated as local malignant recurrence. The authors point out that repeated biopsies, before treatment, are very important for differentiating a malignant recurrence from a benign growth. Conservative treatment can cure these lesions. PMID- 2595011 TI - Invasive carcinoma of the uterine cervix following diagnosis and treatment of in situ carcinoma. Record linkage study within a National Cancer Registry. AB - 56117 women registered in the Swedish National Cancer Registry with the diagnosis carcinoma in situ of the uterine cervix were followed up and the risk for developing an invasive carcinoma of the uterine cervix was studied. The studied cohort provided 453 362 women years at risk. The primary treatment for carcinoma in situ in Sweden is generally conization. Hysterectomy is carried out in relatively few cases and intracavitary radium treatment was given to a limited number during the period studied. Cryosurgery and laser conization were of less quantitative importance during this period. The incidence rates of invasive carcinoma of the uterine cervix were compared with expected rates calculated from the National Cancer Registry. The ratio between observed and expected number of cases of invasive carcinomas of the uterine cervix is roughly 2.5 from the first year of observation after treatment of the in situ carcinoma until 20 years. There seems to be a distinct difference in risk for development of an invasive carcinoma of the uterine cervix for different age groups. In age group 50 years and older at time for treatment of the in situ lesion, 66 cases of invasive cancer were observed against 10.7 expected - O/E = 6.2. In ages 49 years or less, 145 cases were observed compared with 77.4 expected - O/E = 1.9. The conclusion from this study is that women treated for an in situ lesion are at a higher risk for an invasive carcinoma than the common female population and should be carefully followed up for a long time after treatment of the in situ lesion. PMID- 2595012 TI - The fractionated response of mouse stroma after X-rays and neutrons: influence of early vs late expression of damage. AB - The sparing effect of dividing a radiation treatment into many small fractions is different for acutely responding tissues and those which have delayed expression of injury. We have used the Tumour Bed Effect assay (TBE) to investigate the influence of the time of damage expression on the response of the normally quiescent subcutaneous stroma. Implanted tumour cells provide an angiogenic stimulus which forces the vasculature to proliferate. The subcutaneous stroma of the mouse dorsum was irradiated with one to 32 equal fractions of X-rays, followed by a top-up dose of neutrons. CaNT cells were implanted into the treated site either within 3 days or not until 6 months after irradiation, to stimulate the expression of latent injury. The dose-response curves obtained for tumour growth in irradiated sites were much steeper at 1 to 3 days than at 6 months, suggesting some sort of repair of damage during this period. There was no suggestion that repair occurred preferentially after low doses per fraction and the alpha/beta ratio remained unchanged when the expression of stromal injury was delayed. The time of damage expression therefore seems unlikely to explain the difference in the alpha/beta ratios measured for early and late responding tissues. Rather, it seems to be determined by the proliferative status of the tissue at the time of irradiation. PMID- 2595013 TI - Radiofrequency (RF) capacitive hyperthermia combined with radiotherapy in the treatment of abdominal and pelvic deep-seated tumors. AB - Thermal parameters and tumor response were determined in 33 abdominal and pelvic deep-seated tumors which were treated with hyperthermia in combination with radiation therapy. Hyperthermia was applied regionally for a total of 3-14 sessions (mean; 6.4 sessions), using an 8 MHz radiofrequency (RF) capacitive heating device. An average tumor temperature (Tav) of more than 42 degrees C was achieved in 17 (52%) tumors, and intratumor temperatures above 42 degrees C could be maintained for more than 20 min (effective heat session) in 103 (52%) of the 198 heat sessions. Of the 33 tumors, 4 tumors exhibited complete regression (CR), 7 PRa (80-99% regression), 7 PRb (50-79% regression) and 15 NR (less than 50% regression). Tumor response (CR + PRa) was apparently dependent on the thermal parameters. Tumors with Tav of more than 42 degrees C or those receiving more than three effective heat sessions showed a significantly higher response rate than those heated less effectively. This trend was also noted in minimum tumor temperature. As to radiation dose, most of the responders received a total of 60 70 Gy irradiation. The two characteristic features in tumor response in effectively heated tumors, were slow tumor regression and appearance of an intratumor low density area on post-treatment computed tomography. PMID- 2595014 TI - Department of Health and Human Services, National Institutes of Health. Recombinant DNA research: actions under guidelines. AB - This notice sets forth three actions to be taken by the Director, National Institutes of Health (NIH), under the May 7, 1986, NIH Guidelines for Research Involving Recombinant DNA Molecules (51 FR 16958). PMID- 2595015 TI - Department of Health and Human Services, Public Health Service, National Institutes of Health. Recombinant DNA Advisory Committee. Minutes of meeting, January 30, 1989. PMID- 2595016 TI - Department of Health and Human Services, Public Health Service, National Institutes of Health. Recombinant DNA Advisory Committee, Points to Consider Subcommittee. Minutes of meeting, March 31, 1989. PMID- 2595017 TI - Department of Health and Human Services, Public Health Service, National Institutes of Health. Recombinant DNA Advisory Committee, Revision of the NIH Guidelines Subcommittee. Minutes of meeting, June 5, 1989. PMID- 2595018 TI - Field testing genetically modified organisms: framework for decisions. National Research Council executive summary. PMID- 2595019 TI - Recombinant DNA research; proposed actions under guidelines. National Institutes of Health, PHS, DHHS. AB - This notice sets forth proposed actions to be taken under the National Institutes of Health (NIH) Guidelines for Research Involving Recombinant DNA Molecules. Interested parties are invited to submit comments concerning these proposals. These proposals will be considered by the Recombinant DNA Advisory Committee (RAC) at its meeting on October 6, 1989. After consideration of these proposals and comments by the RAC, the Acting Director of the National Institutes of Health will issue decisions in accordance with the NIH Guidelines. PMID- 2595020 TI - [A shortened method for the assay with Centocor radioimmunoassay kit]. AB - We have conducted a series of basic studies about Centocor's CA125 RIA Kit, especially for the conditions of the incubation. The standard curve and the outcome of recovery test gained through the standard method and the shortened method are quite decent. As for the incubation time, it took longer than 20 hours and 6-18 hours inthe standard method and shortened one respectively. As our conclusion, these results suggest that the shortened method can be adopted as a practical one as well as the standard method, provided that careful attention is paid to several peripheral conditions in the assay. PMID- 2595021 TI - [Radiology of AIDS: personal experience]. PMID- 2595023 TI - [MR in the evaluation of schizencephaly]. AB - This study was aimed at evaluating MR utility in the diagnosis of schizencephaly in patients with seizures and developmental delay. In 7 patients, 8 months to 15 years old, MR imaging detected the presence of unilateral (5 cases) and bilateral (2 cases) hemisferic clefts. Moreover, MR imaging allowed the presence of such anomalies as dysgenesis of the corpus callosum, and agenesis of the septum pellucidum to be demonstrated, together with areas of polymicrogyria and heterotopic gray matter. PMID- 2595022 TI - [Involvement of the temporomandibular joint in rheumatoid arthritis]. AB - A tomographic investigation was performed on 51 randomly-selected rheumatic patients, according to American Rheumatism Association criteria. Fourteen males and 37 females, aged 26 to 73 (mean age 50.9) were examined in order to identify the prevalence of temporo-mandibular joint involvement. By means of a special examination form, a contemporary clinical survey of both signs and symptoms of mandibular dysfunction was also conducted: the data were used for calculating the Helkimo anamnestic and clinical dysfunction indices. As for X-ray diagnosis, and original linear and angular analysis was proposed to measure the relationship between condyle and fossa in intercuspal position and during opening: the anterior joint space often increased and protrusive condylar path was reduced in more than 41% of patients. Structural changes were also evaluated by classifying the shape of both the condyle and the glenoid fossa (rounded, wedge-shaped and flattened). A special score was used to quantify these morphological features: only 4% of the whole of joints resulted uninjured. The most involved joint portions were the articular tubercle and the anterior condylar pole. Many cases were demonstrated of marked resorption and remodelling of the condyle, of increased joint space and erosion of the fossa; in other instances, reduced joint spaces and sclerosis were observed, depending on associated degenerative arthritis (usually more painful). Sex and age differences were not significant. Severity of clinical dysfunction and seriousness of the lesions coincided, whereas subjective symptoms were relatively independent. At any rate, the survey demonstrated a clear prevalence of structural, as well as functional, involvement of the temporo-mandibular joint in rheumatoid arthritis and suggested a more careful and multimodal therapeutic approach. PMID- 2595024 TI - [MR (1.5 T) in the evaluation of pancreas transplant rejection]. AB - Graft rejection is the major cause of graft loss following pancreatic transplantation. Early detection of the rejection process is of great importance towards planning effective treatment when transplant recipients present with aspecific clinical findings suggesting rejection. Up to date, the demonstration of pancreatic transplant rejection has been attempted with nuclear medicine and sonography (US). The authors studied high-field (1.5 T) MR potentials in pancreatic transplantation and rejection and correlated MR findings with clinical and laboratory data. Eleven MR scans were obtained from 4 patients with suspected pancreatic graft rejection, and 9 MR images from 4 patients with normal pancreatic allografts. Qualitative image evaluation showed the pancreatic tissue of the patients diagnosed with rejection to be hypointense on T1-weighted scans and highly hyperintense on T2-weighted scans, as compared to normal grafts. Quantitative data were obtained by comparing the signal intensity of pancreatic grafts to that of the nearby muscle. On both T1- and T2-weighted images, pancreatic tissue/muscle signal-intensity ratios were significantly different, in rejecting transplants, from those of normal allografts (p less than 0.001). Our qualitative and quantitative findings suggest the use of MR imaging as a reliable means of detecting pancreatic graft rejection. PMID- 2595025 TI - [MR characterization of breast pathology using inversion recovery sequence]. AB - As yet, a valid tissue characterization of human breast diseases has not been possible with conventional MR techniques. On the basis of the experimental thesis according to which fibroadenomas and carcinomas have a slight, though significant, difference in T1 relaxation times, we employed specific inversion recovery sequences at the T null of the breast glandular and adipose tissues, to enhance the differences in the signal intensities of the various pathologies. We examined 16 (6 cystic dysplasias, 5 fibroadenomas, 3 carcinomas, and 1 phylloid fibroadenoma) selected patients with the above-mentioned sequences in addition to the routine T1- and T2-weighted spin echo sequences. The following conclusions were reached by evaluating the characteristic signal intensities: MR spin echo sequences allow solid lesions to be distinguished from cystic ones; MR inversion recovery sequences allow fibroadenomas to be distinguished from carcinomas with 88% accuracy. PMID- 2595026 TI - [Radiopaque abdominal foreign bodies introduced by the enteral route. 4-year experience]. AB - The aim of this work has been the comparison between the results found in literature and our experience with the introduction of radiopaque foreign bodies by enteral way into the abdomen. The kind of our patients, most of whom were in jail, the sufficient number of cases and the particularity of some of them have convinced us of the soundness of our experience and have persuaded us to briefly report it, with our observations and conclusions. The first thing we want to point out, on the basis of our study, is that the degree of radiopacity of a foreign body is more important than its dimensions as far as its visibility at X ray examination is concerned. Another conclusive point we want to stress is that surgery is often needed to remove foreign bodies introduced by rectum, while most patients who ingest foreign bodies do not need surgery and expel what they have ingested, without complications, by rectal way. PMID- 2595027 TI - [Radiotherapy of recurrences of adenocarcinoma of the rectum after radical surgery: Galliera Hospitals (1976-1985)]. AB - From 1976 through 1985, 68 patients were treated with radiation therapy at Ospedali Galliera, Genoa, Italy, for recurrence of radically-operated rectal adenocarcinomas, most of them in Dukes (Astler, Coller) B2, C1, and C2 stages. The average disease-free interval between surgery and recurrence was 12 months (range 2-144) in the whole group, versus only 6 months in stage C2 patients. Pain relief was obtained in 45 patients (66%), and reduction in recurrence size in 22 (32%), with the following global results: disease progression in 16 patients, no progression/regression in 26, partial regression in 19, complete response in 3, and not evaluable in 4. Twenty-one patients had many contemporaneous distant metastases (2 cases) or within a short period of time after the locoregional recurrence (19 cases). These results lead us to believe that radiation therapy should not be employed in so many cases of radical surgery for rectal adenocarcinoma as it is today, but only in case of locoregional recurrences, as an alternative to postoperative radiotherapy, combined, if needed, with adjuvant chemotherapy. PMID- 2595028 TI - [High-dose gynecologic endocavitary brachytherapy. Technical and dosimetric aspects]. AB - The technical and dosimetric aspects are presented of high-dose intracavitary brachytherapy in gynecology. Fifty-five patients (203 insertions) were examined over two years with a remote loading Selectron HDR 60Co unit installed in a dedicated bunker. The dose to the rectal and bladder markers on AP and LL films was calculated before every irradiation, in order to allow the necessary corrections to be made. Uniform irradiation conditions were obtained at each treatment set-up for both tumoral target and bladder and rectal doses. High-dose intracavitary brachytherapy proved to be a safe, reliable and versatile method from the technical and dosimetric point of view both in the treatment of unoperated gynecological malignancies and in postoperative therapy. PMID- 2595029 TI - Post-traumatic aneurysmal bone cyst of the temporal bone. PMID- 2595030 TI - [Radiological aspects of a case of Madura foot]. PMID- 2595031 TI - [Pulmonary histoplasmosis. Presentation of a case]. PMID- 2595032 TI - [Contribution of computerized tomography and magnetic resonance to the characterization of thymus lipoma. Apropos of a case]. PMID- 2595033 TI - [Calcification of peritoneal cysts in a patient on periodic hemodialysis]. PMID- 2595034 TI - The china clay industry--lessons for the future of occupational health. PMID- 2595035 TI - The role of the alveolar macrophage in asthma. PMID- 2595036 TI - Chronic obstructive airways disease following treated pulmonary tuberculosis. AB - Seventy-one subjects who had previously been treated for tuberculosis up to 16 years before underwent pulmonary function assessment. Evidence of airways obstruction was found in 48 (68%). There was an inverse relationship between the extent of the disease on the original chest radiograph and the forced expired volume in one second (FEV1). A similar inverse relationship between the amount of sputum produced and the FEV1 and the original chest radiograph was also found. Treated pulmonary tuberculosis is a cause of significant chronic obstructive airways disease. PMID- 2595037 TI - Cardiopulmonary function after lobectomy or pneumonectomy for pulmonary neoplasm. AB - Resection of pulmonary tissue for bronchial carcinoma causes a decrease in vital capacity of 15% after lobectomy and 35-40% following pneumonectomy. After operation the lung becomes stiffer and elastic recoil pressure and transdiaphragmatic pressure at TLC increase. Maximum effort tolerance decreases after pneumonectomy with a normal pulmonary artery pressure at rest and an increase in pulmonary artery pressure and in pulmonary vascular resistance on effort, compared to preoperative values. Cardiac output and stroke volume during effort show a decrease after operation with an increase in peripheral arterial blood pressure and in peripheral vascular resistance. Arterial oxygen saturation on effort decreases after pneumonectomy, possibly due to the absolute decrease in diffusing capacity. When comparing resting and exercise values at identical work loads, increases in systemic arterial blood pressure, pulmonary and systemic vascular resistance and arteriovenous oxygen difference were similar although generally less pronounced after lobectomy compared to pneumonectomy; cardiac output, stroke volume and oxygen consumption showed the same tendency to decrease after lobectomy and pneumonectomy. PMID- 2595038 TI - The value of mucus hypersecretion as a predictor of mortality and hospitalization. An 11-year register based follow-up study of a random population sample of 876 men. AB - The value of mucus hypersecretion as a predictor of mortality and hospitalization was studied in a random population sample of 876 men, aged 46-69 years. The cohort was examined in 1974 with the British Medical Research Council questionnaire and lung function tests. A total of 219 men had died between 1974 and 1985. Twenty-seven men died from lung cancer and 14 died from other respiratory diseases. Mucus hypersection was not found to be significantly related to overall mortality after controlling for age, smoking and FEV1. Similarly, mucus hypersection was not a predictor of lung cancer mortality after controlling for age and smoking habits. The predictive value concerning death due to respiratory disease could not be examined because of the limited number of deaths in the cohort from these diseases. Mucus hypersecretion was not significantly related to hospitalization in general. Mucus hypersecretion had a significant predictive value concerning hospitalization due to respiratory disease in general, but the value was insignificant after controlling for FEV1. In contrast to this, mucus hypersecretion was a significant predictor of hospitalization due to COPD, even after controlling for FEV1. We conclude that the predictive value of mucus hypersecretion concerning mortality is of no value. Concerning morbidity, our results show that, although secondary to airflow obstruction, mucus hypersecretion must be viewed as an indicator of severity of COPD. PMID- 2595039 TI - Sedation for fibreoptic bronchoscopy: comparison of alfentanil with papaveretum and diazepam. AB - Sedation for fibreoptic bronchoscopy should produce optimal conditions for the operator, patient comfort and rapid recovery allowing early discharge home. We have compared a regimen producing 'light' sedation with a more traditional regimen producing 'deep' sedation. Seventy-six patients undergoing fibreoptic bronchoscopy under topical anaesthesia were randomized to receive either light sedation with the short acting opiate, alfentanil (median dose 1.1 mg, range 0.5 2.6 mg) or deep sedation with a combination of papaveretum (median dose 10 mg, range 5-15 mg) and diazepam (median dose 8 mg, range 0-20 mg). Both techniques gave equally good operating conditions, although patients given alfentanil coughed less than those given papaveretum and diazepam (U = 2.814 P less than 0.01). Patients recorded their degree of apprehension on a visual analogue scale prior to sedation and the actual degree of comfort experienced after recovery. There was no significant difference between apprehension or comfort between the groups. This was despite a higher degree of amnesia for an irrelevant object shown during the bronchoscopy in the deeply sedated group (chi 2 = 21.084 P less than 0.001). Patients given alfentanil performed significantly better in a modified Romberg test (chi 2 = 4.357 P less than 0.05) and a visualisation test (t = 3.035 P less than 0.01) two hours after the bronchoscopy. Alfentanil produced good operating conditions, patient comfort, less cough and a more rapid recovery, compared to the deep sedation regimen, and is an ideal sedative for fibreoptic bronchoscopy. PMID- 2595040 TI - Aminophylline toxicity--how many hospital asthma deaths does it cause? AB - Aminophylline administration was compared in 43 patients who died from asthma and 43 matched controls who were admitted, suffering from acute asthma, to hospitals in the North East Thames Region. A computer program, which used information about individual characteristics, medical history and drug intake, was employed to calculate the serum theophylline levels which were likely to have resulted from the hospital treatment each patient received. Toxic theophylline levels were estimated to have occurred in 21% (9/43) of fatal cases and 7% (3/43) controls. Details of four patients who died when their serum theophylline levels were likely to have been very high are presented. Six fatal cases suffered gastro intestinal bleeds during their final illness: four of these had theophylline levels which were calculated to have been toxic at the time of bleeding. PMID- 2595041 TI - Comparison of pulse oximeters in healthy sleeping infants. AB - Four commercially available pulse oximeters were compared on normal infants to determine incidence and correct identification of movement artefact, and to assess their other features, in order to guide the potential user in the most appropriate choice of a machine to suit their purposes. Measurements of arterial oxygen saturation by pulse oximetry are distorted by movement artefact. During five one hour recording periods, over 100 artefacts occurred with each machine. The incidence of movement artefact differed between oximeters. Twice as many occurred when the Criticare 500 was used. The four oximeters differed in their ability to identify artefacts. The Novametrix 500 was best able to do this. A visual display aided observer recognition of artefacts. Other features of the different machines are described. An expansion of the use of pulse oximetry beyond the intensive care unit is suggested. PMID- 2595042 TI - Bronchiolitis obliterans organizing pneumonia. PMID- 2595044 TI - Non-cardiogenic pulmonary oedema associated with pyrimethamine. PMID- 2595043 TI - Bilateral spontaneous pneumothoraces complicating AIDS-related Pneumocystis carinii pneumonia. PMID- 2595045 TI - Allergic granulomatosis without asthma: a rare 'forme fruste' of the Churg Strauss syndrome. PMID- 2595046 TI - Hydropneumothorax in sarcoidosis. PMID- 2595048 TI - Chest physiotherapy: time for reappraisal (1) PMID- 2595047 TI - Pleural complications of acute pancreatitis--an autopsy study. PMID- 2595049 TI - [Plastic surgery of the anterior cruciate ligament: experimental study of intra articular aramid fibers in dogs]. AB - The authors explored the possibility of replacing an anterior cruciate ligament with an aramid fiber (Kevlar) implant. This study was performed in intra articular site in 9 dogs and the average implantation period was 5 months. Studies were carried out by macroscopic, photon microscopy, and electron microscopy examination of the samples obtained at the time the animals were sacrificed. Clinical and radiographic studies of the knees were performed in order to assess functional consequences. Overall, the results showed a partial or complete rupture of 10 neoligaments out of the 17 studied ligaments; on the other hand, osseous anchorage and reintegration in the intra-articular zone appeared satisfactory. Kevlar fiber only partially meets the performance specifications for an artificial ligament intended to serve as an anterior cruciate ligament substitute. Some positive results have encouraged the authors to carry on further this experimental study. PMID- 2595051 TI - [Surgical reduction of the external ligament for chronic instability of the tibio tarsal joint. Apropos of 58 reviewed cases]. AB - Between 1975 and 1986, 75 cases of surgical tightening of the lateral ligament have been performed for chronic instability of the ankle. 58 of them have been reviewed with a mean delay of 36 months (extremes of 6 months to 6 years). Surgery corrected completely the instability four out of five times. In six patients there still remained more or less incapacitating pain. Talo-navicular movements were constantly preserved, as well as that of the sub-talar joint, except in six cases where it was slightly diminished. The results have been excellent in 18 cases; very good in 18 cases; good in 6 cases; mild in 8 cases and poor in 4 cases. Furthermore, four patients who originally had an excellent or very good results have subsequently presented with a recurrence of joint laxity and instability following a new severe ankle sprain. X-ray results were less satisfactory as the joint laxity was only partially controlled (average tilt of 7 degrees). But all joint laxities except one have been improved by this type of surgery. After failure of proprioceptive rehabilitation which must be performed systematically, surgical tightening of the lateral ligament can be proposed, and should be preferred to peroneus brevis ligamentoplasties, which are more traumatic and less physiological. PMID- 2595050 TI - [Fractures of the thoracic spine (T1-T10). Apropos of 105 cases]. AB - Thoracic spine (T1-T10) fractures can be considered a specific entity owing to the anatomic features of the rib cage and the spinal canal. During a nine year period, the authors treated 105 such fractures. The thoracic spine fractures included 57 (54.2 per cent) compression fractures, 21 (20 per cent) comminuted (burst) fractures, 3 (2.8 per cent) flexion-distraction fractures, and 24 (23 per cent) fracture-dislocations. Five lesions, termed "fracture-dislocations by an oblique shearing force", were characterized by considerable displacement and the absence of neurologic injury. 35.2 per cent of the patients had injuries at multiple levels. The frequency of associated thoracic (26.5 per cent) and scapular injuries (20 per cent) reflected involvement of the entire thoracic cage. The frequency of neurologic impairment (30.4 per cent including 20 per cent complete paraplegia) reflects the particular vulnerability of the dorsal spinal cord. 32 per cent of the patients presented one or more thoracic effusions (hemomediastinum, hemothorax) related to parietal hematoma and/or hematoma at the fracture site. Functional management of 47 patients led to recovery of a painless spine without kyphotic deformity. Conservative treatment was often difficult because of associated parietal lesions; the 10 patients treated in this manner had only moderate reductions that maintained poorly in time, but had no major painful sequellae. A posterior approach was used for 42 patients with unstable or neurotoxic fractures because this permitted a complete decompression down to the posterior wall, when necessary by a "wide laminectomy". The anterior approach was reserved for purely anterior compression (3 cases) or residual compression after an initial posterior procedure (2 cases). Cotrel-Dubousset instrumentation (used in 7 cases) was particularly indicated because it offers the advantages of Harrington rods (31 cases) while providing better stabilization. This prevented later loss of reduction and obviated the need for a postoperative brace. PMID- 2595052 TI - [Superior radio-cubital congenital synostosis. Computed tomographic scanning studies and value of osteotomy fixation using an external fixator]. AB - The purpose of this case report was to describe the radiological features by computed tomography and a modification in the fixation of the rotation after the usual transverse osteotomy: an external fixation was used; it allows post operative vascular assessment with the possibility to derotate the correction in case of circulatory or neural impairment. PMID- 2595053 TI - [Arthroscopic meniscectomy complicated by lesions to the popliteal artery and vein]. AB - Endoscopic surgery can replace operative procedures. The evolution of arthroscopy leads to realize intra articular surgery more and more complicated. However, any surgical procedure involve some risks, and surgeons have to be prudent in use of new instruments or new technics. These need a radio surgical environment adapted to all surgery. PMID- 2595055 TI - [Knee arthrodesis using tibio-femoral rods following ablation of the septic total prosthesis]. AB - A technique of knee arthrodesis is described, using a fixation by medullary tibio femoral rods introduced in the supra-malleolar region of the tibia. This procedure has been used with success as a salvage procedure after removal of four septic total prostheses of the knee. It allowed an early weight bearing and was indicated in cases where external fixator had failed or was contra-indicated. PMID- 2595054 TI - [A case of recurrent sciatica following a free adipose tissue graft]. AB - The authors present a case of recurrence of sciatic pain in a patient operated upon for lumbar disc herniation two days before. It was related to the migration to the vertebral canal of the fat tissue graft used ward for preventing fibrotic tissue invasion from outside. After removal of the graft, healing was uneventful. PMID- 2595056 TI - [Detachment of the triceps in the treatment of elbow stiffness in extension in children]. AB - A total triceps disinsertion technique was used in children for treating elbow stiffness in extension, subsequent either to antibiotics injections administered in the arm, or to some old unreduced dislocations met in our experience. The disinsertion allowed the recovery of a good range motion in the post-injections stiffnesses and facilitated the reduction in old unreduced dislocations. The triceps detached in this manner preserves its bio-mechanical integrity, avoiding at the same time the risk of intra-articular hypertension. Used 17 times (in 12 post-injections retractions and 5 unreduced dislocations), this technique provided interesting results. PMID- 2595057 TI - [Security in the specialty]. PMID- 2595058 TI - [Evaluation of post-traumatic coma using evoked potentials]. AB - In 130 cases of post-traumatic coma a study of multimodality evoked potentials (MEP) was carried out shortly after the traumatism (within 72 h). According to the morphology of the records they were classified in grades (I-IV) in agreement with Greenberg et al. The worst grade of EP in the different types was related to the outcome at 6 months, distinguishing between focal lesions and diffuse lesions. Only a group (22.9%) of the 109 patients in which the auditory brain stem evoked potentials (ABEP) could be studied, showed severe disorders (grade III-IV). There was a significant correlation between the ABEP grades and the outcome in the focal lesions (p less than 0.001). In the diffuse lesions the ABEP grades did not show significant differences with the outcome. A 22.4% of the patients with diffuse lesions had some visual evoked potentials (VEP) in grades III-IV against almost the double (41.6%) in the focal lesions. The grades of the VEP in the focal lesions did not have differences with outcome and in the diffuse lesions they did (p less than 0.05). Approximately half of the cases with focal lesions and one third of the diffuse lesions showed severe disorders (grades III IV) of the somatosensory evoked potentials (SEP). In the two types of lesions there were significant differences with the outcome (p less than 0.001) and (p less than 0.01). The multimodality evoked potentials (MEP) are useful for predicting the outcome, especially in the patients where the neurological examination is impossible. Among the different modalities, the SEP were shown to be more predictive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2595059 TI - [Effect of the peridural methadone concentration in postoperative analgesia]. AB - The analgesic characteristics of 3 to 6 mg epidural methadone administered in two different concentrations for postoperative analgesia have been compared in two homogeneous groups of patients submitted to surgical procedures on trunk or legs. Methadone was given at a concentration of 0.1% in group I (70 patients) and diluted in 10 ml saline in group II (35 patients). Methadone doses were calculated on the basis of age and weight of the patient and the performed surgical procedure. Mean latency for analgesia was 25 +/- 11 min in group I and 28 +/- 13 min in group II. The duration of the analgesia was significantly longer (p less than 0.01) in group I (9.7 +/- 5.6 h) than in group II (5.7 +/- 2.4 h). Side effects were not frequent and without clinical significance in both groups. Epidural methadone is an effective method for postoperative pain relief. Drug concentration modifies the duration of the analgesia and concentration of 0.1% gives better results than more diluted preparations. PMID- 2595061 TI - [Intraoperative bradycardia in a case of Lown [correction of Long]-Ganong-Levine syndrome. PMID- 2595060 TI - [Anesthesia and lumbar epidural anesthesia in an infant with third-degree burns]. AB - Epidural route is widely used in adults for injection of drugs, but it is not so often used in pediatric patients. We present the case of a 8 month old burned infant who received anesthesia and analgesia through a lumbar epidural catheter. The insertion of epidural catheter is described. Two surgical procedures were performed under epidural anesthesia with 0.5% bupivacaine an epinephrine 1:200.000 (2.5 mg/kg). 16 hours of postoperative analgesia was obtained with epidural morphine (0.05 mg/kg). No side effects were seen. We analyze the uses of epidural anesthesia in pediatric patients, the catheter care in the burned child, the hemodynamic changes observed during anesthesia and the results of peridural morphine. PMID- 2595062 TI - [Treatment using physostigmine of disorientation and agitation caused by dehydrobenzperidol]. PMID- 2595064 TI - [Resuscitation or post-anesthesia recovery unit: a single concept?]. PMID- 2595065 TI - [Abstracts of the 22d National Congress of Cardiology. (25-28 October 1989) Oviedo]. PMID- 2595063 TI - [Poisoning by organophosphates]. PMID- 2595066 TI - [Anatomo-pathological changes in the biliary system caused by povidone iodide. Experimental study]. AB - In this report, the possible effects of povidone iodide (PVP-I) on the biliary system are studied in an experimental study using dogs. We used 20 dogs divided in two study groups. Light microscopy and electronic scanning microscopy (SEM) were used. We demonstrated that in the tied choledochus, intermittent washings with PVP-I caused a notable injury pattern on the biliary system. PMID- 2595067 TI - [Biliary secretion. Significance of hypercholeresis from the surgical point of view]. AB - In patients carrying a Kehr tube choledochostomy, the surgeon may observe, but rarely, important hypercholeresis, non-bile-acid dependent, in people with severe advanced chronic hepatic diseases or persistent cholestasis. The amount of bile flowing to the outside can reach two liters and more daily. We have seen this in two patients with compensated hepatic disorders and in another suffering from light cholestasis produced by choledocholithiasis. We have also found the same in three other people with liver and the main biliary extrahepatic tract completely normal. This hypercholeresis is continuous and subject to rapid increases relative to the ingestion of food. Such increases are related to gastrointestinal hormones, specially secretin, which is produced when portions of gastric chyme enters the duodenum. PMID- 2595068 TI - [Liver cirrhosis: study of the evolution of mortality in Spain (1951-1983)]. AB - In this study we review the mortality in Spain from liver cirrhosis between 1951 and 1983. There was a decrease in the general mortality due to this cause, while in the study of mortality by sexes there was only a tendency to decrease in males but not in females. When an analysis was made according to age groups, there was a tendency to rise in younger patients, while there was a lowering in older ones. We also studied comparatively the mortality data for the same cause in France. PMID- 2595069 TI - [Ascites and pleural effusion. Study and follow-up of 79 patients]. AB - We reviewed 79 patients with a picture of pleural effusion (EP) and ascites, who represented 8% of a total of 982 pleural effusions studied. Liver cirrhosis (CH), 37 cases (47%), disseminated carcinomatosis, 31 cases (39.5%), and congestive heart failure, 6 cases (7%), were the main causes. We made two groups of liver cirrhosis: A) liver cirrhosis with hydropic decompensation, 12 patients (15%), and B) liver cirrhosis with an additional complication added to the above, 25 patients (31.5%), this being infectious in 88% of the cases. In the B group there were cases of left hydrothorax, more features of effusion and a lower survival at 3 months of follow-up than in tha A group. Effusions of neoplastic origin were most frequently seen in tumors of the ovary, digestive system, lymphomas and undetermined origin. In malignant effusions, the cytology was positive in pleura in 60% and in ascites in 55%. Twenty percent of peritoneal fluids and 47% of pleural effusions were serohemorrhagic and 100% and 88%, respectively, were of exudative nature. In liver cirrhosis the ascites was serofibrinous and transudated (100% in group A and 85.5% in B) and the pleural effusion was a serofibrinous transudate except in the cases in which there was an added infection. We confirm the ominous prognosis of the coexistence of pleural effusion and ascites. PMID- 2595070 TI - [Training gastroenterologists for the year 2000]. PMID- 2595071 TI - [Justification for subtotal esophagectomy in late spontaneous esophageal rupture]. AB - A patient is presented who was operated for an intestinal obstruction and developed in the immediate postoperative period Boerhaave's syndrome. Subtotal esophagectomy with bipolar exclusion was performed. We discuss the advantages of radical surgery, even in advanced cases, if the size of the lesion justifies it, as compared to more conservative therapeutic attitudes. PMID- 2595072 TI - [Pneumatosis coli vs. deep cystic colitis]. AB - We present the case of a 63-year-old female who with no previous history presented with episodes of self-limited diarrhea without fever, general repercussions, abnormal elements or tenesmus. Biochemistry: no abnormality. Parasite and feces culture: negative. Colonoscopy: at 20 to 40 cm from the anal margin were found polypoid lesions covered with normal mucosa. Barium enema confirmed the presence of multiple lacunar defects and possible parietal gas. Biopsy: submucous cysts with foreign body type giant cells. Mixed infiltrate. The differential diagnosis was made between intestinal enterogenous cyst, lymphangioma, retractable mesenteritis and deep cystic colitis, concluding with pneumatosis coli that evolved favorably. PMID- 2595073 TI - [An infrequent association: carcinoma of the colon and hypernephroma]. AB - We present a case of an infrequent association of colonic carcinoma and hypernephroma. Despite the relative infrequency of this kind of association, they are now commonly reported, so we should not consider multiple primary carcinomas as a sporadic phenomenon, but rather as a frequent phenomenon with important clinical implications. PMID- 2595074 TI - [Congestive gastropathy and sclerotherapy]. PMID- 2595075 TI - [Study of diet-induced thermogenesis using telethermography in normal and obese subjects]. AB - It is well established that food ingestion induces increased thermogenesis, but the site in man of this increased heat production is still not known. Recent data suggest that brown adipose tissue or the liver may have an important role in this phenomenon. Since recent research provides some evidence to suggest that activation of thermogenesis in a specific organ or tissue may determine increased skin temperature in the surrounding region, we have studied skin temperature in the dorsal interscapular and in the liver regions using infra-red thermography in groups of normal and obese subjects before and after administration of oral glucose. In a separate group of normal subjects we studied oxygen consumption before and after glucose administration. While oral glucose produced a clear increase in thermogenesis, no ascertainable variation was observed in body temperature and, therefore, of heat dispersion in any of the regions studied in either normal or obese subjects. PMID- 2595076 TI - [Septic thrombosis of the cavernous sinus. Presentation of a clinical case]. AB - This paper describes a case of cavernous sinus septic thrombosis with cerebellar complication. The CNS was involved after a primitive piodermitis of the face. The diagnostic tools employed in the management of the case and the therapeutic procedures in the acute phase and in the convalescence are discussed. The patient completely recovered after chemotherapeutic treatment. PMID- 2595077 TI - [Correlative evaluation of electrocardiographic changes and spirometric parameters in pulmonary cardiopathy secondary to chronic obstructive bronchopneumopathy]. AB - EKG is not considered a sensitive procedure for diagnosis of chronic pulmonary heart disease (CPHD). We performed a correlative study between EKG signs and spirometry in chronic obstructive pulmonary disease (COPD). Fifty-six consecutive in-patients (M 52, F 4, age 59.1 +/- 13.1 yrs) with COPD and echocardiographic/roentgenologic signs of right ventricular enlargement were studied. An EKG score system (0-6) was developed considering: 1) AQRS greater than or equal to 90 degrees; 2) P waves greater than or equal to 2.5 mm; 3) R wave V1 greater than or equal to 7 mm or R/S V1 greater than or equal to 1; 4) R/S V5 less than or equal to 1; 5) RV strain pattern; 6) RBBB. Significant (p less than 0.01) linear correlations were observed between: a) AQRS vs FEV1 (r = 0.59); b) AQRS vs FEV1/FVC% (r = -0.61); c) R/S V5 vs FEV1, (r = +0.38); d) EKG score vs FEV1 (r = -0.42); e) EKG score vs FEV1/FVC% (r = -0.40). Significant relationship between EKG score and spirometry suggests that this criterium can be useful for a more reliable ecg diagnosis of CPHD. PMID- 2595078 TI - [Treatment of hypophyseal prolactin-secreting macroadenomas]. AB - We investigated a group of 26 patients with prolactin-secreting pituitary macroadenomas. Seventeen underwent neurosurgical operation alone, nine were also submitted to medical therapy with bromocriptine 7.5 mg/day, immediately after the operation. Patients presented similar clinical and biological characteristics. Fourteen patients without medical therapy showed a persistent hyperprolactinemia and the tumor recurred in 8 of these 17 patients. Of the 9 patients receiving medical and surgical therapy, only 1 presented persistent hyperlactinemia and none relapsed. Our results suggest that combined sequential surgical and medical therapy may be useful in the management of patients with prolactin-secreting pituitary macroadenomas. PMID- 2595079 TI - Natural anti-TNP antibodies from rainbow trout interfere with viral infection in vitro. AB - Normal and viral-infected rainbow trout (RT) were tested for serum antibody activity against self and nonself antigens. Particularly high titres of anti trinitrophenyl (TNP) antibodies were noted, as in other fish species. To analyse this, the anti-TNP antibodies were isolated by affinity chromatography and their capacity to interfere with viral infection in vitro was studied. We selected RT fibroblasts as target cells, and two common pathogenic viruses in trout, a rhabdovirus, viral haemorrhagic septicaemia virus (VHS) and a birnavirus, the infectious pancreatic necrosis virus (IPN). Anti-TNP antibodies were examined for their capacity to neutralize VHS and IPN viruses. Data obtained show that the anti-TNP antibodies, even at high concentrations, only partially neutralized virus. In contrast, when anti-TNP antibodies were assayed for their protective activity using RT fibroblast cells infected with VHS or IPN viruses, results showed high protective activity, regardless of serum origin or of the virus used, when the antibodies were added to the cell culture after viral infection. Therefore, our experiments indicate that the protective activity does not seem to be due to a direct interaction of the antibodies with the viruses. It is suggested that virus-modified cell surface self structures exhibit new epitopes which interact with the anti-TNP antibodies. Such an interaction would allow anti TNP antibodies to participate in a non-specific defence mechanism against viral infection. PMID- 2595080 TI - The membrane protein compositions of lipopolysaccharide- or lipoprotein-activated B lymphoblasts from C57BL LPS-responder and non-responder mice are qualitatively indistinguishable. AB - Membrane proteins from murine lymphoblasts enriched by the Triton-X114 procedure were analysed by 2-dimensional gel electrophoresis to reveal proteins differentially expressed in mitogen-reactive subpopulations of B cells. The protein patterns from C57BL/6 normal and nude mice and from the B10.Sc.Cr LPS-non responder strain, activated with lipopolysaccharide (LPS) or an analogue of lipoprotein, were virtually identical when run under strictly parallel conditions. These experiments raise the question as to whether mitogen receptors, serologically and functionally found to be membrane-bound, do exist as membrane proteins. PMID- 2595081 TI - In vitro interactions between murine macrophages and Eimeria falciformis sporozoites. AB - A short-term (2 h) assay was used to investigate the in vitro fate of Eimeria falciformis sporozoites in murine peritoneal macrophages. In minimal medium, uptake of sporozoites was low by both normal (naive) and immune macrophages. However, when heat-inactivated serum from immune mice was added to the incubation medium, sporozoite uptake was much more efficient. Sporozoite lysis was observed only in immune macrophages and required both antibodies and complement. Pretreatment of immune macrophages with chloroquine inhibited sporozoite lysis and resulted in an accumulation of sporozoites within the cells. Immunoabsorption assays revealed that IgG2a was the major isotype mediating entry of sporozoites into macrophages, both in early (6 days post-primary) and late (second) infections. PMID- 2595082 TI - Human monoclonal autoantibodies produced by hybridomas derived from lymphocytes of multiple sclerosis patients. AB - The aim of this study was to characterize autoantibodies produced in vitro by peripheral blood lymphocytes (PBL) of patients affected with multiple sclerosis (MS). We studied supernatants from man-mouse hybridomas established by fusion of PBL from 6 MS patients (group I) and from 13 individuals free of any neurological pathology (group II) with the mouse myeloma cell line P3X63 Ag8-653. They were screened for human IgG or IgM production by ELISA. Autoantibody activity against lymphocytes was studied by cell-binding ELISA. Anti-tissue reactivity was assessed by indirect immunofluorescence assay (IFA) on human cerebellum and peripheral nerve as well as on a panel of 8 non-nervous tissues. Additional ELISA tests were performed on 4 purified cellular antigens. Among 522 supernatants in group I, 13.7% contained Ig, mainly IgM, as compared to 25% among 1212 supernatants in group II; 8.3% in group I and 6.7% in group II contained anti tissue autoantibodies. Antibodies against purified cellular antigens were found in 6% of the supernatants in group II versus 7% in group II. One human monoclonal anti-astrocyte antibody from group I was further studied. This IgM lambda (SAN-7) was particularly polyreactive and recognized glial fibrillar acid protein and other intermediate filaments, as well as tubulin and myosin. Moreover, cross reactivity was observed with a hapten (TNP-BSA). PMID- 2595083 TI - Are the nonprecipitating asymmetric antibodies autoprotective and regulatory antibodies? One opinion. PMID- 2595084 TI - Intradermal challenge of Icelandic horses with extracts of four species of the genus Culicoides. AB - Twenty-three Icelandic horses were challenged with extracts of four species of biting midges: Culicoides pulicaris, C chiopterus, C obsoletus and C impunctatus. Fourteen of the tested horses were affected with summer eczema. The horses were challenged intradermally with 0.1 ml of whole-body extracts of midges at a concentration of 0.01 or 0.005 per cent weight/volume. The skin reactions were measured after 30 minutes, 60 or 180 minutes and four, 24 and 48 hours after injection. Antigen titration showed that the reaction was dependent on the antigen concentration. Eight of nine unaffected horses failed to respond to any of the four antigens; the remaining animal responding to two of the four antigens. Ten of the 14 affected horses responded to at least three of the four antigens, while two of the animals in this group failed to respond to any. The mean responses to C chiopterus, C obsoletus and C impunctatus, read after 30 minutes, 60 minutes and four hours were significantly higher in the affected horses than in the unaffected horses. A significant difference was also found in the mean response to C chiopterus and C impunctatus, read after 24 hours. PMID- 2595085 TI - Mechanisms of platelet destruction in immune-mediated thrombocytopenia: in vitro studies with canine platelets exposed to heterologous and isologous antiplatelet antibodies. AB - Normal canine platelets coated with heterologous or isologous antiplatelet antibody were interacted with viable canine neutrophils in vitro. Platelet phagocytosis was assessed by detecting nitroblue tetrazolium (NBT) reduction, measuring uptake of opsonised 51Cr-labelled platelets, and electron microscopy. The NBT reduction and uptake of 51Cr-labelled opsonised platelets were markedly increased. Electron microscopy revealed phagocytosis of antibody-coated platelets and their degradation intracellularly. Exposure of canine platelets to rabbit anti-canine platelet antibody in vitro produced morphological changes in platelets and caused serotonin release. Serotonin was not released in the absence of antiplatelet antibody or in the presence of normal rabbit gamma-globulin. Morphological changes in the platelets included disappearance of alpha and dense granules and exaggeration of the open canalicular system. These observations indicate that circulating platelets may be vulnerable to an antiplatelet antibody and that antibody-mediated phagocytosis of platelets is an important mechanism in the pathogenesis of immune-mediated thrombocytopenia. PMID- 2595086 TI - Ostertagia ostertagi infection in the calf: effects of a trickle challenge on appetite, digestibility, rate of passage of digesta and liveweight gain. AB - The effects of a trickle challenge with the equivalent of 10,000 infective Ostertagia ostertagi larvae per day on appetite, digestibility, rate of passage of digesta and liveweight gain were investigated in 12 calves assigned to infected, pair-fed control and ad libitum-fed control groups. Digestibility of cellulose, nitrogen, organic matter and dry matter was determined using insoluble acid detergent fibre as a marker on two occasions during the study: (i) Between days 31 and 38, when abomasal dysfunction was greatest; and (ii) between days 52 and 58, beginning approximately one week after anthelmintic treatment (day 46). Rate of passage of digesta was measured using chromium mordanted hay, fed to each calf after each digestibility study period. Voluntary feed intake of the infected group was significantly reduced from day 37 with the greatest depression (77 per cent) occurring just before anthelmintic treatment. The drop in appetite was responsible for nearly 73 per cent of the difference in liveweight gain between the infected and ad libitum fed control groups. The apparent digestibility coefficient of nitrogen was significantly depressed (22 per cent) in the infected group though was restored to control levels by anthelmintic treatment. The rate of passage of digesta was significantly reduced in both pair-fed control (50 per cent) and infected (74 per cent) groups. Anthelmintic treatment increased the latter though only to pair-fed control group levels. It is suggested that the marked hypergastrinaemia seen in the infected calves may have been in part responsible for the decreased rate of passage of digesta and in turn for the drop in appetite. PMID- 2595087 TI - Ostertagia ostertagi infection in the calf: effects of a trickle challenge on the hormonal control of digestive and metabolic function. AB - Metabolic effects of a trickle challenge with the equivalent of 10,000 infective Ostertagia ostertagi larvae per day were investigated in 12 calves allocated to infected, pair-fed control or ad libitum-fed control groups. Changes in hormone levels reflecting abomasal, pituitary and pancreatic function were monitored using radioimmunoassay techniques previously validated for use in cattle. A range of metabolic profile parameters and blood metabolites was also measured. Feed intake of the infected calves began to decline as blood gastrin and pepsinogen levels reached a peak. The depression in appetite recorded in this group was responsible for significant increases in plasma urea and non-esterified fatty acid levels and associated with an increase in growth hormone/insulin ratio. No significant difference in glucagon levels was recorded between groups. A decline in blood albumin values was also shown in the infected group and associated with a drop in nitrogen digestibility. A significant depression in circulating calcium levels was related to either the hypoalbuminaemia or impaired mineral absorption in the intestine. A decrease in plasma cholesterol values in the infected group was associated with changes in digestive function. PMID- 2595088 TI - Growth of Babesia bovis parasites in stationary and suspension cultures and their use in experimental vaccination of cattle. AB - A combination of stationary culture and suspension culture was used to produce litre quantities of Babesia bovis parasites suitable for use as live vaccine. The Australian vaccine strain of B bovis, Ka, was maintained continuously in microaerophilus stationary phase (MASP) cultures, and for a short period in batch and flow-through spinner flask cultures. Although continuous culturing was not achieved in spinner flasks, the production of litre quantities of heavily parasitised erythrocytes was achieved more simply than by using MASP cultures. Ka strain parasites were maintained continuously in MASP culture for 174 days without altering their virulence or immunogenicity when compared to calf-derived parasites. Cultured parasites also survived storage at 4 degrees C for six days in basal medium, adding to their potential usefulness as a live vaccine in field situations. PMID- 2595089 TI - Effect of African trypanosomiasis on plasma cortisol and thyroxine concentration in goats. AB - Changes in plasma cortisol and thyroxine (T4) levels were measured weekly in female goats experimentally infected with Trypanosoma congolense. Values for plasma cortisol (range 10 to 25 nmol litre-1) and T4 (range 65 to 120 nmol litre 1) were within normal ranges in all goats before infection and in control animals throughout the 24 weeks of study. Cortisol/T4 ratios of 0.23 to 0.15 (or 1:4 to 1:7) were obtained. In the infected goats a significant increase in cortisol and decline in T4 were simultaneously observed within one week of the onset of parasitaemia and fever. A peak cortisol/T4 ratio of 2.0 (2:1) was obtained four weeks after infection when cortisol levels rose to 59.0 +/- 8.9 nmol litre-1 and T4 declined to 29.4 +/- 2.2 nmol litre-1. Thereafter the mean levels fluctuated but remained high (over 30 nmol litre-1) for cortisol and low (under 50 nmol litre-1) for T4 up to 18 weeks after infection. Both hormones tended to return to normal levels towards the end of the study. The changes in mean cortisol levels showed a significant inverse correlation with changes in T4 (r = -0.57, P less than 0.001, n = 26). It is suggested that in trypanosomiasis, hypothalamic stress causes increases in plasma cortisol levels and at the same time suppresses the activity of the thyroid gland. PMID- 2595090 TI - Influence of selenium status in merino weaners on resistance to trichostrongylid infection. AB - Weaned merino lambs, grazing pastures low in selenium, were used to investigate the effect of selenium status on immunity to trichostrongylids. Six weeks following selenium supplementation to 14 of the 27 sheep using intraruminal selenium pellets, 5000 Ostertagia circumcincta and 5000 Trichostrongylus colubriformis larvae were administered orally to all sheep. At four weeks after infection, the mean total worm burden in the selenium supplemented sheep (5537 +/ 343, n = 14) was not significantly different (P greater than 0.05) from that in the unsupplemented sheep (5614 +/- 374, n = 12) and faecal worm egg concentrations were also similar in the two treatment groups. At this time, mean red cell glutathione peroxidase activities in the supplemented and unsupplemented groups were 430 and 11 U g-1 haemoglobin, respectively, and clinical white muscle disease had been observed in the latter group. These results suggest that increasing selenium status of selenium deficient sheep by the use of intraruminal selenium supplementation, has a negligible effect on resistance to an artificial challenge infection of O circumcincta and T colubriformis. PMID- 2595092 TI - Radionuclide angiocardiography in the normal dog: first-pass studies. AB - The first pass of a bolus of radioactivity (99mTc) through the heart and lungs was studied in 27 anaesthetised healthy adult mongrel dogs, using a gamma camera with a computer on-line. Bodyweights ranged from 9 to 60 kg, heart rate from 108 to 150 beats min-1. Quantitative analysis revealed that the distribution volume (DV) of the labelled blood, the cardiac output (CO), the stroke volume (SV) and pulmonary blood volume (PBV) were almost proportional to the bodyweight. Specific results were: DV 120 ml kg-1, CO 136 ml kg-1, SV 1.11 ml kg-1, PBV 6.9 ml kg-1. The pulmonary transit time varied between 1.0 and 3.6 seconds. Clinical applicability of the method, including visual inspection of camera images and quantitative analysis of a time-activity curve of the lung, was demonstrated for one dog with an aortic stenosis and another with a left-to-right shunt. PMID- 2595091 TI - Role of harderian glands in resistance against Mycoplasma gallisepticum challenge. AB - Harderian glands of one-day-old chickens were surgically removed. At one week old, these chickens and controls from which these tissues were not removed, were vaccinated intranasally with a temperature-sensitive mutant of Mycoplasma gallisepticum. Humoral and local immunity were measured by means of antibody in sera and tracheal washings, respectively. Protection was measured by resistance to intra-air-sac challenge with the S6 strain of M gallisepticum. There was no discernible difference in either humoral or local antibody response between vaccinated chickens from which the glands had been removed and control birds. In addition, both groups were significantly protected against air-sac challenge compared with unvaccinated controls. These results indicate that removal of the Harderian glands neither affects the production of antibody to M gallisepticum, nor alters the effectiveness of temperature-sensitive M gallisepticum vaccination. The role that the Harderian glands play in resistance to M gallisepticum is therefore questioned. PMID- 2595093 TI - Radionuclide angiocardiography in the normal dog: equilibrium studies. AB - Equilibrium radionuclide ventriculography was applied in 27 healthy anaesthetised dogs (9 to 60 kg) after labelling the blood pool with 99mTc, using a gamma camera with a computer on-line. Quantitative analysis of the calibrated ventriculogram provided the following left ventricular parameters: the end diastolic volume (EDV), the ejection fraction (EF), the possible degree of regurgitation and as velocity indices the peak ejection and peak refilling rates (PER and PRR). Averaged results were: EDV 1.8 ml kg-1; EF 0.59; PER 4.3 EDV s-1; PRR 3.75 EDV s 1. Visual inspection of the camera images may reveal abnormal wall motions and dilatation of heart chambers. PMID- 2595094 TI - Biochemical changes in the jejunal mucosa of dogs with exocrine pancreatic insufficiency following pancreatic duct ligation. AB - The effects of exocrine pancreatic insufficiency on the small intestinal mucosa were examined in dogs following pancreatic duct ligation. There were no significant changes either in villus architecture or enterocyte height after duct ligation, but numbers of bacteria in duodenal juice increased then subsequently decreased following treatment with exogenous pancreatic enzymes. Pancreatic insufficiency resulted in a considerable increase in the proportion of microvillar membrane proteins of molecular mass over 200 kDa from 3.3 +/- 4 per cent (mean +/- SEM) to 13.6 +/- 7.2 per cent, and this decreased to 6.9 +/- 5.2 per cent following pancreatic enzyme supplementation. However, anticipated increases in activities of maltase and sucrase were not observed following duct ligation, and there was a reduction in lactase activity which was reversed by pancreatic supplementation. Activities of marker enzymes for the other subcellular organelles showed relatively minor or no changes throughout the study. These findings are consistent with a specific role for pancreatic enzymes in the post-translational processing of intestinal microvillar membrane proteins, and suggest that reduced degradation of brush border proteins in the absence of pancreatic secretions may be masked by quantitative and qualitative changes in the intestinal microflora. PMID- 2595095 TI - Urethral pressure profilometry in the anaesthetised bitch: a comparison between double and single sensor recording. AB - A comparison was made between urethral pressure profiles obtained using a single sensor and 'subtracted' urethral pressure profiles resulting from double sensor recordings in 50 bitches. There were small but significant differences in the functional profile lengths and maximum urethral closure pressures between the two types of recording. The differences were partially explained by a significant fall in the intravesical pressure recorded during profilometry and variations due to respiration. The profiles from single and double sensor recording were of equal significance in the diagnosis of sphincter mechanism incompetence. PMID- 2595096 TI - Comparison of methods for the sampling and isolation of toxigenic Pasteurella multocida from the nasal cavity of pigs. AB - The efficacy of detecting toxigenic Pasteurella multocida from nasal swabs of slaughtered and live pigs was assessed. The isolation of toxigenic P multocida from nasal cavities of slaughtered bacon pigs from two herds with atrophic rhinitis was reduced by immersion in the hot water tank by 25 per cent and 75 per cent. Individual sows from one of the infected herds were repeatedly swabbed to find the best method of isolating toxigenic P multocida. Toxigenic P multocida were isolated from 50 per cent of cotton swabs inoculated on to selective medium the same day. After 24 hours in the post, 45 per cent of cotton swabs placed in transport medium, 38 per cent of alginate swabs dissolved in transport medium and inoculated into mice, and 36 per cent of the dissolved swabs inoculated directly on to selective medium yielded toxigenic P multocida. These bacteria were isolated from only 25 per cent of cotton swabs held in transport medium at 10 degrees C for 48 hours to simulate prolonged postage times; from slaughtered pigs a similar reduction in isolation was seen with swabs kept for 24 or 48 hours. The reduced isolation caused by a delay before culture was associated with an overgrowth of other flora. The development of this flora was prevented by storage of swabs at 4 degrees C in the laboratory or by the use of cool boxes for postage. PMID- 2595097 TI - Effect of posture and anaesthesia on the distribution of pulmonary perfusion and lung configuration in beagle dogs. AB - To investigate the effect of posture and anaesthesia on the topographical distribution of pulmonary perfusion in canine lungs, the changes in lung shape, configuration and regional perfusion were assessed in healthy beagle dogs, using a repeated 99mTc perfusion scintigraphic procedure. The general shape of the lung images was similar in standing and prone postures, except for a relative increase of the more ventral zone in the prone posture, ascribed to vertical flattening of the lung associated with enlargement of the ventral zones. Configuration changes revealed a shift of the parenchyma towards the more caudal parts in the prone posture, which suggests a parenchymal compression of the paradiaphragmatic lung zones. The prone posture induced a decreased perfusion to the caudal third of the lung. Anaesthesia induced significant changes in lung shape without an obvious direction. The perfusion to the more ventral as well as to the more cranial zones was reduced. Differences in the perfusion distribution are thought to be mainly due to the pressure exerted by the abdominal content through the diaphragm and to the shift of the blood towards better ventilated lung regions. PMID- 2595098 TI - 19-nortestosterone detection in canine plasma after intramuscular administration of 19-nortestosterone phenylpropionate. AB - A proven radioimmunoassay method for monitoring 19-nortestosterone (nandrolone) was combined with high pressure chromatographic fractionation on a microparticulate silica gel using 1,2 dichloroethane/ethanol as the mobile phase. Plasma levels of 19-nortestosterone were monitored for seven days after intramuscular administration of nandrolone phenylpropionate (1.5 mg kg-1) to a beagle and a German shepherd dog. After 24 hours the plasma level in both bitches was 20 ng ml-1 and reverted to baseline after the fourth day after injection. Nandrolone was shown to be the only detectable exogenous steroid present in the post injection plasmas and could be distinguished from any potential cross reacting metabolites. The radioimmunoassay method can therefore be applied to the evaluation of nandrolone in the management of canine chronic renal disease in the bitch. PMID- 2595099 TI - Changes in the collodiaphyseal angle with growth in the fowl (Gallus domesticus). AB - The angle formed between the femoral neck and shaft is referred to as the collodiaphyseal angle. In man, the angle decreases during growth and is frequently different in the right and left limbs. This study examines the collodiaphyseal angle in another biped, the growing fowl. Three groups (A, B and C) of growing fowls were examined. The weight difference between birds would alter the forces applied to the growing proximal femur and at the end of the experimental period the birds in group B weighted three times those in group A. Nevertheless, in all three groups the collodiaphyseal angle decreased from 120 degrees to 108 degrees over the growth period. Where there was a difference in collodiaphyseal angle between right and left limbs the angle was more frequently greater in the right. Bodyweight apparently had little effect on the development of collodiaphyseal angle in the fowl, possibly due to the trocharteric/antitrocharteric articulation reducing the stresses applied to the femoral neck. PMID- 2595100 TI - Calcium fluxes across the wall of the ovine reticulorumen in vivo. AB - Calcium fluxes were measured, in vivo, in both directions across the ovine reticulorumen wall of four sheep when the luminal potassium concentration was either 30 mmol litre-1 or 90 mmol litre-1. Neither fluxes were affected by an increased potassium concentration although net magnesium absorption was decreased (PO less than 0.05) and the transmural potential difference was increased (P less than 0.01) under these conditions. The results obtained suggest that, unlike magnesium, calcium is transported bidirectionally across ovine ruminal tissue independently of the transmural potential difference across the rumen wall. PMID- 2595101 TI - An improved TLC method for the detection of flunixin in equine serum. AB - A method for flunixin detection in equine serum extracts involving thin layer chromatography, spraying the chromatogram with alkaline sodium hypochlorite solution and heating with a detection limit of 50 ng ml-1 is described. PMID- 2595102 TI - Value of two-dimensional echocardiography in the identification of pulmonary hypertension in chronic obstructive lung disease. AB - Thirty-three patients suffering from chronic obstructive lung disease (COLD) were submitted to right heart two-dimensional echocardiographic (2D-ECHO) and hemodynamic study. By the subcostal approach, the right ventricle outflow tract including the pulmonary vessels was visualized in 85% of the patients. Most parameters measured on the right ventricle and pulmonary vessels were significantly higher than those recorded in the healthy control group. Very significant correlations were observed between the mean pulmonary artery pressure (PAP) and the following 2D-ECHO parameters: diameter of the pulmonary artery at valve level (r = 0.62; p less than 0.001); supravalvular diameter of the pulmonary artery (r = 0.44; p less than 0.03); diameter of the left branch of the pulmonary artery (r = 0.48; p less than 0.05); diameter of the right branch of the pulmonary artery (r = 0.39; p less than 0.05), and between the PAP and PaO2 (r = -0.66; p less than 0.001). Furthermore, the sensitivity, specificity, and accuracy of 2D-ECHO measurements were calculated to assess the presence of pulmonary hypertension. Overall sensitivity was 65%, specificity 75%, and accuracy 67%. However, by combining the value of PaO2 with that of the pulmonary valve by means of the multiple regression analysis, sensitivity increased to 84% in identifying pulmonary hypertension. Such data demonstrate that the 2D-ECHO study of the right heart in COLD patients has to carefully measure the dimensions of the pulmonary valve and the great pulmonary vessels, as their modification are mainly linked with the presence of pulmonary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2595103 TI - Role of lactic acidosis in the ventilatory response to heavy exercise. AB - The purpose of this study was to determine the role of lactic acidosis in the ventilatory response to heavy exercise above anaerobic threshold. Seven subjects ingested either NaHCO3 or CaCO3 at a dose of 300 mg/kg body weight and ran on a motor-driven treadmill at a work load corresponding to 90% of VO2max and above anaerobic threshold for a period of 5 min while minute ventilation and PETCO2 were recorded breath by breath. A total of 10 runs, 5 with CaCO3 and 5 with NaHCO3 in a randomized and blind order, were done in each subject. Statistical analyses of the effects of the chemicals on minute ventilation during the 15 s between min 4.75 and 5 of exercise showed that the differences in ventilation did not reach statistical significance (p greater than 0.05) in 5 of the 7 subjects. Venous pH measurements at the end of exercise revealed a significant increase with NaHCO3 (p much less than 0.05). It is concluded that lactic acidosis is not an essential determinant of ventilatory response to heavy exercise above anaerobic threshold in the majority of the subjects. PMID- 2595104 TI - Theophylline serum levels in children with bronchial asthma after administration of slow release theophylline as open or closed capsules. AB - Theophylline serum levels were studied after oral administration of slow release theophylline (Talofilina) in children with bronchial asthma. The children received the drug as closed capsules or as granules, obtained by opening the capsules, for 1 week in each form. The mean dose used was 8.6 mg/kg every 12 h. The theophylline blood levels at 4, 8 and 12 h after drug ingestion were significantly lower when granules from open capsules were used. Our recommended dose of Talofilina for Brazilian children is 16 mg/kg/day, if administered as closed capsules, every 12 h. On open capsule administration every 12 h, the total daily recommended dose is 20 mg/kg/day. PMID- 2595105 TI - Effect of ascorbic acid on increased bronchial responsiveness during upper airway infection. AB - We investigated the acute effect of ascorbic acid on histamine bronchial responsiveness (PC 20: concentration causing a 20% fall in FEV1) in 9 hospital staff members with upper respiratory tract infection (URI) and cough. Subjects were examined within 5 days from the start of illness and 6 weeks after. On day 1, the reproducibility of PC20 was assessed by 2 consecutive inhalation challenges 1 h apart; the two values were closely related (r = 0.96, p less than 0.001). Five subjects had bronchial hyperresponsiveness (PC20 less than 8 mg/ml histamine). On the following day, PC20 was measured before and 1 h after oral intake of 2 g ascorbic acid. Vitamin C produced a significant increase in average PC20 (p less than 0.01) from 7.8 +/- (SE) 1.2 to 25.1 +/- (SE) 1.2 mg/ml. None had airway hyperresponsiveness after treatment. Six weeks after the onset of URI, bronchial responsiveness was normal in all the subjects but one. The mean PC20 was 15.5 +/- (SE) 1.25 mg/ml, significantly higher than during URI (p less than 0.05); after ascorbic acid it increased nonsignificantly to 25.7 +/- (SE) 1.35 mg/ml. Our results indicate that vitamin C inhibits the transient increase in bronchial responsiveness occurring in otherwise normal subjects during URI. PMID- 2595107 TI - Humoral immunity alterations after environmental asbestos exposure. AB - The inhabitants of Metsovo in northwestern Greece have been environmentally exposed to asbestos from childhood because they had been using a tremolite containing material for whitewash, without knowing its consistency. As a result, they have a very high incidence of calcified pleural plaques and malignant pleural mesothelioma but no pulmonary fibrosis. In the present study we examined certain aspects of the humoral immunity in the serum of 109 individuals: levels of immunoglobulins, C-reactive protein and complement components, as well as the presence of antinuclear antibodies, rheumatoid factor, antibodies to extractable nuclear antigens, to ds-DNA and to cardiolipin. Our results show that, compared to controls, those exposed to asbestos have increased IgG and C3 levels. Those with pleural plaques have, in addition, increased IgA levels and an increased incidence of antinuclear antibodies. The results of the study suggest that nonoccupational asbestos exposure affects humoral immunity. The presence of pleural plaques accentuates this effect. PMID- 2595106 TI - Failure of aminophylline and salbutamol to improve respiratory muscle function and exercise tolerance in healthy humans. AB - We investigated the effects of intravenously administered aminophylline (A; 6 mg/kg over 20 min, followed by 0.9 mg/kg/h), salbutamol (S; 4 micrograms/kg over 20 min, followed by 3 micrograms/kg/h) and placebo (P; saline solution) on the strength of the respiratory muscles, the ventilatory endurance and the exercise tolerance in 7 healthy humans. Neither A nor S caused bronchodilation, as shown by the lack of change in FEV1. The strength of respiratory muscles, as measured by maximal inspiratory pressure (MIP), and the ventilatory endurance, as measured by sustainable inspiratory pressure (SIP), were not statistically different after A (MIP: 136.5 +/- SE 11.6 cm H2O; SIP: 104.2 +/- 8.4 cm H2O or after S (MIP: 135.7 +/- 11.5; SIP: 107.1 +/- 10.4) compared to after P (MIP: 127.1 +/- 10.1; SIP: 105.0 +/- 5.9). Significant changes in 12-min walking distance, perceived exertion rate, anaerobic threshold, maximal work output, maximal O2 uptake were observed neither after A nor after S. The exchange ratio and heart rate were higher after A and S than after P at some steps of a progressive, symptom limited, treadmill-based exercise test. This might be the result of metabolic or cardiovascular adaptations elicited by these drugs. We conclude that A or S at therapeutic concentrations have no clinically relevant beneficial effects on ventilatory muscle function and exercise tolerance in healthy subjects. PMID- 2595108 TI - Visual results and complications after retinal reattachment in the acute retinal necrosis syndrome. The influence of operative technique. AB - The authors compare the complications and visual results encountered in a consecutive series of 16 eyes undergoing retinal reattachment surgery for retinal detachment associated with the acute retinal necrosis syndrome. Eight eyes were treated with scleral buckling, vitrectomy, and cryotherapy with or without gas injection. Eight consecutive eyes (with one exception) were treated by the combination of vitrectomy, gas injection and laser photocoagulation with or without primary lensectomy and not subjected to scleral buckling as a primary procedure. The final reattachment rate was 93.8% (15 of 16 eyes) with no significant difference between the primary scleral buckle group (87.5%) and the non-buckle group (100%). Retinal reoperation and complication rates were higher in the primary buckle group and final visual acuities better in the non-buckle group despite comparable preoperative characteristics. PMID- 2595109 TI - Pseudophakic retinal detachments. The relationships between retinal tears and the time following cataract surgery at which they occur. AB - The types and locations of retinal tears associated with 268 pseudophakic retinal detachments were studied as a function of the time at which they occurred following cataract surgery. Retinal detachments occurring more than two years following cataract extraction were significantly more likely to have their most posterior retinal break located at the posterior margin of the vitreous base than at or behind the equator. This distribution of tears was not observed in detachments occurring within six months of cataract surgery, with equatorial tears being significantly more common in early onset detachments than in those occurring after two years. The anterior tears which cause most retinal detachments long after cataract extraction are due to persistent chronic traction upon the vitreous base rather than to acute posterior vitreous detachment. PMID- 2595110 TI - Retinal macroaneurysms treated with the yellow dye laser. AB - Retinal macroaneurysms, and their sequelae of retinal hemorrhage, exudate, edema, and serous detachment of the macula, may lead to decreased central visual acuity. We studied twelve patients with retinal macroaneurysms and decreased or threatened central vision who underwent laser photocoagulation of the macroaneurysm using the yellow (577 nm) wavelength of an ophthalmic tunable dye laser. In all cases, the macroaneurysm was "obliterated", with resolution of hemorrhage, exudate, edema, or serous macular detachment; in eight of the twelve cases, the visual acuity improved following treatment. There were no complications due to the photocoagulation. PMID- 2595112 TI - Integrity of the blood-ocular barrier after intravitreal gas injection. AB - The authors studied the effect of various intravitreal gases on the integrity of the blood-ocular barrier using a fluorophotometric technique. The gas (0.3 ml) was injected into the vitreous cavity of a pigment rabbit after paracentesis. Air and two long-acting gases, sulfur hexafluoride and perfluoropropane, were studied. The eyes that received only paracentesis served as controls. Fluorescein concentrations in the anterior chamber were determined by slit-lamp fluorophotometer 30 minutes following intravenous fluorescein administration. Fluorophotometry was repeated on days 1, 3, 7, and 14 after the gas injections. The eyes that received sulfur hexafluoride and perfluoropropane showed increased aqueous fluorescein concentrations in comparison with the control eyes and the air-injected eyes, although conventional slit-lamp biomicroscopic examination detected no anterior chamber inflammatory signs in these eyes. The aqueous fluorescein leakage decreased to the normal level after the intravitreal gas bubble was absorbed. These results suggest that intravitreal gas bubbles induce subclinical breakdown of the blood-aqueous barrier, which becomes re-established soon after the gas is absorbed. PMID- 2595111 TI - Retinal laser photocoagulation. Effect of rate of energy delivery. AB - Three monkeys were treated with krypton red laser photocoagulation in a manner simulating treatment of a choroidal neovascular membrane. One eye of each monkey was treated by employing immediately the power level needed to produce a lesion judged biomicroscopically to be of sufficient intensity (Method A). The fellow eye was treated by starting with lower power levels and then gradually increasing to the level needed to produce a similar-appearing lesion (Method B). Parameters of spot size and treatment duration were kept constant. Animals were sacrificed three days, eight days, and four months after treatment. Both methods of treatments spared the overlying ganglion cell layer in all fundus locations, but Method A induced cell loss in the inner nuclear layer while Method B spared it. Since reaching the clinical endpoint for Method B required fewer spots at the highest power level, the number of spots at the highest power level is probably the most important factor in determining degree of inner retinal absorption. Since both methods of treatment resulted in satisfactory closure in the choriocapillaries, the histopathologic differences may not be clinically important. PMID- 2595113 TI - Rpe cell migration into intact vitreous body. AB - Retinal pigment epithelial (RPE) cells were obtained from human cadaver eyes and grown to confluence in 16 mm wells. A sterile intact rabbit vitreous body was isolated and placed on the RPE monolayer. RPE cells with fibrocyte-like morphology appeared over the RPE monolayer within 4 to 6 days. These rapidly proliferating cells were observed to extend cellular processes and migrate into the vitreous body. Migration of the RPE cells progressed over 20 to 40 days, at which time bipolar RPE cells were found in multiple layers of the vitreous body. The contractile properties of the migrating RPE cells were evident as 24% of vitreous bodies contracted into a dense cellular gel. This study provides a model of migration of RPE cells in the vitreous and allows study of the interaction of RPE with the intact vitreous gel. PMID- 2595114 TI - Bull's-eye maculopathy and negative electroretinogram. AB - The authors studied four patients with a bull's-eye maculopathy and otherwise normal fundus. A single-flash electroretinogram (ERG) with an intense white light stimulus in the dark showed a normal a-wave but reduced b-wave amplitude (negative ERG). Other findings common to all four patients were initially normal visual acuity, subsequent progressive decrease in visual acuity, mild to moderate deficiency of color vision, normal peripheral visual field, relatively well preserved cone ERG, normal 30-Hz flicker ERG, normal EOG, near emmetropia and selective involvement in males. Cone dystrophy, retinitis pigmentosa, congenital retinoschisis, congenital stationary night blindness, and Batten's disease were excluded. The correlation between this disease and benign concentric annular macular dystrophy is discussed. PMID- 2595116 TI - Evolution time and longitudinal studies of the anti-S-antigen antibody titers in retinitis pigmentosa. AB - Sixty-six patients with retinitis pigmentosa (forma simplex) and 37 control patients were studied for titers of anti-S-antigen auto-antibodies by means of the enzyme-linked immunosorbent assay technique (ELISA). A longitudinal study showed a positive significance (P less than 0.01) which demonstrated the uniformity of the data obtained. Comparison of the anti-S-antigen titers of the patients and controls revealed a statistically significant difference (P less than 0.001) between both populations. The relationship between the time of evolution of retinitis pigmentosa and the anti-S-antigen titers also showed a statistically significant difference (P less than 0.005). These results show both a rise in the anti-S-antigen antibody titers in relation to the evolution time of retinitis pigmentosa and a uniformity in the data obtained in the anti-S-antigen antibody longitudinal study carried out. PMID- 2595115 TI - Attenuating effects of diazepam on the electroretinogram of normal humans. AB - Response/log I curves were obtained under conditions of dark-and light-adaptation in seven normal male volunteers. For each subject, a baseline electroretinogram (ERG) was recorded. In the same afternoon, a second ERG was obtained after 0.05 mg/kg diazepam, and a third ERG was recorded following 0.10 mg/kg diazepam. Under conditions of dark-adaptation, the following dose-dependent changes were identified: 1) Diazepam attenuated the rod b-wave peak amplitude and increased its implicit time; 2) The dark-adapted longer wavelength cone a-wave and 'blue cone' b-wave showed an increased implicit time; 3) All oscillatory potentials showed an increased implicit time. Under conditions of light-adaptation, dose dependent decreases in peak amplitude and delays in implicit time were observed for the a- and b-waves. The effects of diazepam on the human ERG were more profound under conditions of light- than dark-adaptation. PMID- 2595118 TI - [Transesophageal echocardiography]. PMID- 2595117 TI - [Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody]. PMID- 2595119 TI - [Clinical characteristics of unstable angina in 162 consecutive cases]. AB - We surveyed the clinical characteristics, treatment, and prognosis of 162 patients with unstable angina, who were admitted to our center between 1985 and 1987. There were 112 males and 50 females, with a mean age of 65 years. The clinical characteristics according to the American Heart Association classification were new angina of effort in 21%, changing pattern in 61%, and new angina at rest in 18% of the patients. ECG recordings during attacks of angina were obtained in 70%, and ST elevation was detected in 11%, ST depression in 54%, and T wave abnormality in 5%. Coronary arteriography performed in 42% of the patients revealed single vessel lesion in 21%, two vessel lesion in 10%, three vessel lesion in 5%, and left main trunk lesion in 3% of the patients. Seventy seven percent of the patients were controlled by medical therapy, including nitrates, calcium antagonists, and, in some cases, beta blockades. Three percent of the patients were controlled with intra aortic balloon pumping in addition to medical therapy. Coronary artery bypass graft surgery (CABG) was performed in 6% of the patients. Since 1987, percutaneous transluminal angioplasty (PTCA) was introduced in our center and PTCA was performed in 9 patients (6%). Restenosis of the dilated portions of the coronary artery was observed and PTCA was again performed in 2 of 9 patients (22%). All patients who received CABG or PTCA survived and have been free from angina or myocardial infarction. Non-fatal myocardial infarction occurred in 10 cases (5.6%) and fatal infarction occurred in one patient (0.6%). PMID- 2595120 TI - [Influence factors on coronary collateral development]. AB - In order to evaluate the influence factors on coronary collateral development, we compared various factors between two groups. Group I consisted of the 69 patients performed coronary angiography within 6 hours after the onset of acute myocardial infarction (MI) and Group II consisted of the 56 patients without MI because having good collaterals nevertheless whose one coronary artery was totally occluded or had a 99% stenosis. Group I (24/69, 35%) had a higher frequency of Diabetes mellitus than Group II (11/56, 20%) and had a lower frequency (30/69, 43%) of multivessel disease than Group II (39/56, 70%). The patients having angina duration more than 6 months were more in Group II (37/56, 60%) than in Group I (18/69, 26%). No significant differences existed between these two groups in age, smoke, hyperlipidemia and hypertension. In conclusions, the patients with good collateral have high frequency of multivessel disease and long history of angina pectoris. Diabetes mellitus is a inhibit factor on coronary collateral development. PMID- 2595121 TI - [Myocardial free wall rupture and thrombolytic therapy in acute myocardial infarction]. AB - We investigated the relation between myocardial free wall rupture and thrombolytic therapy in 200 patients with acute myocardial infarction (AMI). Ten of 200 patients (5.0%) were complicated with cardiac rupture, and all of them died within 70 hours after the onset (29% of the deceased after AMI). The pathophysiologic study of 5 patients undergoing autopsy after cardiac rupture was performed. In 4 patients receiving thrombolysis, autopsy revealed massive hemorrhagic infarction and teared lesion near the center of infarcted area. We assessed that the location of teared lesion might be influenced by broad hemorrhagic infarcted area following thrombolytic therapy. The incidence of cardiac rupture was slightly higher in the group receiving thrombolysis in the early stage of AMI than conventional treatment group. Among the patients receiving thrombolytic therapy, some cases revealed markedly increased fibrinolytic activity. This suggested that such elevated fibrinolytic activity might induce massive hemorrhagic infarction and might be an important factor contributing to the cardiac rupture. Thrombolytic therapy has been frequently reported to improve cardiac function and prognosis, but our study suggests that thrombolytic therapy must be evaluated moreover as one of the risk factors of cardiac rupture. PMID- 2595122 TI - [Aortic wall injury and thrombogenesis in catheterization: experimental study]. AB - Arterial and venous catheterization is a very useful procedure in the diagnosis of heart diseases. However, some complications with thrombogenesis have been reported. Two kinds of Mikaelson-type non-heparin-coated angiographic catheters (with 6.5 Fr. and 80 cm length) were used for the experiments. One was of polyurethane (PUC) and the other of polyethelene (PEC). Eight experimental dogs were used for each group. The catheter was inserted into the ascending aorta through the femoral artery. No antithrombogenic drugs were given to the animal. One hour later, sodium heparin (100 U/kg) was administered intravenously. The animal was sacrificed by acute exanguination. The aorta was opened longitudinally. The position of the thrombi on the aortic wall was macroscopically observed and the weight of the thrombi attached to the catheters were measured. A piece of the aorta at each level was excised for light and scanning electron microscopic observations. Mural thrombi of various lengths still remained on the aortic wall of every dog after the removal of the catheters. Microscopic observation revealed that the mural thrombus was formed on the aortic wall, where the endothelial cells had peeled off and the internal elastic membrane was partially destroyed. SEM observation also showed that fibrin network on the aortic wall where the endotherial cells were peeled off. Microscopic observation of aortic wall also revealed intimal tears, inner elastic membrane injury and bleeding in the elastic membrane. This damage could worsen leading to dissection of the aorta, thrombosis of the abdominal organs. The injury is considered due to mechanical irriation by the catheter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2595123 TI - [Assessment of the relation between bone mineral metabolism and mitral annular calcification or aortic valve sclerosis in elderly patients]. AB - We assessed the effect of bone mineral metabolism on mitral annular calcification (MAC) and aortic valve sclerosis (AVS) in elderly patients. Both MAC and AVS were derived by 2-D echocardiography and bone mineral content (BMC) of vertebral body was obtained by quantitative computed tomography using a calibrated phantom system. The 162 patients were classified according to the echocardiographic finding into three groups; CNT group consisted of the 79 control patients (31 males, 48 females) without MAC or AVS. MAC group: 42 patients (11 males, 31 females) with MAC, and AVS group: 41 patients (19 males, 22 females) with AVS. The results were as follows: 1) The incidence of MAC and AVS in both males and females were increased in proportion to aging. 2) The incidence of MAC in females (31%) was higher than that of males (18%). 3) The AVS in males (31%) was more frequent than that in females (22%). 4) In females of eighth and ninth decades, the BMC in MAC group was significantly decreased than that in CNT group, but not different in males. 5) In both males and females, the BMC in AVS group was not significantly different from that in CNT group. These results suggest that the MAC may be attributed to the ectopic deposit, probably related to the de calcification from the spinal bone. On the other hand, the AVS may be caused by the other factors, mainly prolonged and sustained pressure or stress loading. PMID- 2595124 TI - [Surgical treatment of ventricular septal rupture following myocardial infarction in an aged patient with bronchial asthma]. AB - Urgent surgery for ventricular septal rupture following myocardial infarction in a 75-year-old female with bronchial asthma was successfully performed. On Feb 28, 1988, she had chest pain, and was admitted 5 days later because of the appearance of heart murmur. Pansytolic murmur (Levine 4/VI) on 3 LSB and piping sound on both lung fields was heard, ECG showed acute anteroseptal infarction. Right heart Swan-Ganz catheterization revealed left to right shunt, and the diagnosis was ventricular septal rupture following acute anteroseptal infarction with bronchial asthma. The initial hemodynamic condition was not serious, but soon after the diagnosis was confirmed, IABP was inserted and operation was indicated because of the advanced age, high shunt ratio (70%) and complication of bronchial asthma. The operation was performed a day after septal rupture. The perforation in the ventricular septum of the apex was sutured with a xenopericardium patch by mattres sutures through a left ventricle approach, and the ventricular wall was closed with this patch together. The postoperative course was uneventful, and the patient was discharged on the 43rd day after the operation. PMID- 2595125 TI - [Progression of a new lesion after percutaneous transluminal coronary angioplasty -report of a case]. AB - A-62-years-old man was admitted our hospital because of angina at rest and during effort. Coronary angiography revealed 25% fixed stenosis in Seg. 6, 90% in Seg. 7, 75% in Seg. 10, and 50% in Seg. 12. Percutaneous transluminal angioplasty was performed for segment 7 and complete revascularization was obtained finally. Two and a half months later, progressive lesion occurred in the segment proximal to the angioplasty site (Seg. 6). The manipulation of the guiding catheter in the coronary artery proximal to the PTCA site might have developed atherogenesis in this area. So we must consider the possibilities of both restenosis and new lesions when one has the recurrence of ischemic symptoms after coronary angioplasty. PMID- 2595126 TI - [A case of coronary artery fistula with angina pectoris]. AB - A case of coronary artery fistula with myocardial ischemia is reported. A 57-year old-man was admitted to our hospital complaining of anterior chest pain on exertion. Submaximal Treadmill exercise showed the depression of ST segment in leads II, III, aVF, V5 and V6. 75% stenosis of right coronary artery (segment 2) and congenital coronary artery fistula originating from both the right and left coronary arteries were demonstrated by the coronary arteriography. One abnormal artery was originated from proximal portion of the right coronary artery (segment 1) and entered the pulmonary artery trunk. Another one was originated from proximal portion of the left coronary artery and terminated in angiomatous plexus which then communicated with the pulmonary artery trunk. We speculate that myocardial ischemia resulted from decreased right coronary blood flow due to coronary steal and proximal organic stenosis of right coronary artery. Recently, the reviews of coronary artery fistula are increasing, but coronary artery fistula with myocardial ischemia is relatively rare. This case was followed with medical therapy, because antianginal agents were effective. Operative coronary ligation may be necessary, if he has angina or high output heart failure during follow-up. PMID- 2595127 TI - [A case of cardiac myxoma associated with congenital oculocutaneous albinism]. AB - This case is a 43 year-old-woman of left atrial myxoma associated with oculocutaneous albinism, who was admitted to our hospital because of nocturnal cough everyday. Electrocardiogram showed normal sinus rhythm and complete right bundle branch block. Chest X-ray disclosed slight enlargement of left atrium. Echocardiography revealed the left atrial pedunculated tumor, arising from atrial septum, prolapsing into left ventricle during diastole, which was coincided with lucent tumor by levophase of pulmonary arteriography. Feeder artery of this tumor was visualized by right coronary arteriography. Cardiac catheterization represented normal pressure of right-sided heart. Thus the diagnosis of left atrial myxoma was established. At the operation, radical excision of the base of tumor and septum and patch closure was undergone. The gross morphology and microscopic findings were consistent with myxoma. PMID- 2595128 TI - [Significance of decreased washout rate in hypertrophic cardiomyopathy by exercise Tl-201 myocardial scintigraphy]. AB - A clinical significance of decreased washout rate (WR) in hypertrophic cardiomyopathy by exercise thallium-201 myocardial scintigraphy was evaluated. Thirty-six patients with hypertrophic cardiomyopathy and normal coronary angiogram were categorized into 3 groups according to initial distribution (ID) and WR: decreased ID group (17 patients, ID group), normal ID but decreased WR group (9 patients, WR group) and normal ID and normal WR group (10 patients, N group). RESULTS: (1) Cardio-thoracic-ratio and left ventricular end-diastolic pressure were higher in WR group than in other 2 groups. (2) Resting ejection fraction and left ventricular end-diastolic volume index did not differ in three groups. (3) Exercise ejection fraction was increased in N group, whereas it was not increased in ID or WR groups. It was increased in 47% of ID group, but were decreased or not changed in all patients of WR group. In conclusion, decreased WR in patients with hypertrophic cardiomyopathy may strongly suggest left ventricular myocardial damage. PMID- 2595129 TI - [Study on the genesis of posturally induced crackles from hemodynamic data--in patients with ischemic heart disease having normal respiratory function]. AB - The presence of fine crackles is suggestive of heart failure in patients without pulmonary disease. We have been interested in the clinical observation that fine crackles are frequently detected when posture was changed from sitting to supine positions or in patients going from sitting position to supine position with passive legs elevation in patients without obvious evidence of heart failure. We named these crackles, "the posturally induced crackles (PIC)". We have already reported that PIC was frequently detected in patients with ischemic heart disease. The present study was performed to estimate the mechanism of the genesis of PIC and to clarify its significance. Seventy-three patients with ischemia heart disease were included in this study. Pulmonary sounds were auscultated in sitting and supine positions and during passive elevation of both legs in a supine position. Patients were divided into 3 groups according to the presence or absence of fine crackles, i.e., those in whom fine crackles were not detected in either position (PIC (-)), those in whom fine crackles were detected in a supine position or during passive elevation of both legs, but not in a sitting position (PIC (+)), and those in whom fine crackles were detected even in a sitting position (Persistent crackles). We measured various hemodynamic parameters (cardiac index, RA pressure, PA pressure and PAW) and parameters of pulmonary circulation (pulmonary blood volume, pulmonary "venous" compliance) in these 3 groups and comparisons were made between them.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2595130 TI - [Coronary hemodynamics in a patient developing chest pain in the middle age in congenital coronary-pulmonary fistula]. AB - Recently reports of congenital coronary-pulmonary fistula have been increasing with the wide-spread use of coronary angiography. However, the cause of the angina sometimes seen as a chief complaint in coronary fistula has not been well demonstrated although it has been suggested that coronary steal phenomenon accounts for it. This report documented coronary hemodynamics in a patient who came to develop anterior chest pain in the middle age owing to congenital coronary-pulmonary fistula, measuring coronary flow before and after the fistula closure operation. A 35-year-old woman suffered from a sudden onset of severe anterior chest pain in April, 1986. She was referred to our hospital on suspicion of ruptured aneurysm of Valsalva. Auscultation disclosed continuous murmur at 3 LSB, but no evidence of ruptured aneurysm of Valsalva was detected by echocardiography nor aortography. Coronary angiography showed both left and right coronary fistula into the stem of pulmonary artery and otherwise normal angiogram. Great cardiac vein flow (GCVF) measured with regional thermodilution method was 25 ml/min at rest (70 bpm) and 30 ml/min during rapid atrial pacing (150 bpm) before the operation, and 30 ml/min (78 bpm) and 58 ml/min (150 bpm) after the operation, respectively. Before the surgery, anterior coronary resistance (CRant) was higher than that in normal subjects at rest and remained almost steady during atrial pacing. After the surgery, CRant was still higher at rest but remarkably reduced during pacing of 150 bpm. These findings suggest that the gradual increase in peripheral coronary resistance for a long time may lead to the inducement of coronary steal in the middle-later age in patients with coronary fistula. PMID- 2595131 TI - [A case of rapidly progressive pulmonary pulmonary hypertension in a 14-year-old girl]. AB - A 14-year-old girl was admitted with chief complaints of edema and chest pain. She had hepatomegaly, but did not have heart murmur and accentuation of the pulmonary component of the second heart sound. The electrocardiogram showed right axis deviation, negative T wave in V3,4 and ST depression in III, aVF. But right ventricular hypertrophy was not dominant. Chest radiography showed a cardiothoracic ratio of 54% and a slight prominence of proximal pulmonary arteries. The edema was soon diminished only by the diuretics, but it appeared again without the diuretics. At the cardiac catheterization 3 months after the onset of symptoms, the pulmonary arterial pressure was 150/85 mmHg and the pulmonary resistance was 3,232 dyn/sec/cm5. The right atrial pressure was 9.5 mmHg and oxygen saturation at the pulmonary artery was 31.0%. Prostaglandin E1 reduced the pulmonary artery pressure only a little, but raised the systemic pressure. The patient was treated with several vasodilators, but her condition deteriorated rapidly and she developed severe right ventricular failure. She died only 8 months after the onset of symptoms and 5 months after the catheterization. At autopsy, histological examination demonstrated intimal fibrotic thickening of the small-sized pulmonary arteries and organizing thrombus. But there was not plexiform lesion. Heart failure was easily improved when she was first admitted. But after 3 months the cardiac catheterization revealed that her condition was already severe. Several vasodilators was not effective to such a rapidly progressive primary pulmonary hypertension. PMID- 2595133 TI - [Biochemistry of blood coagulation and fibrinolysis underlying pulmonary thrombosis and embolism]. PMID- 2595132 TI - [Incidence of pulmonary thromboembolism in Japan]. PMID- 2595135 TI - [Underlying diseases and risk factors in pulmonary thromboembolism]. PMID- 2595134 TI - [Mechanism of pulmonary thromboembolism]. PMID- 2595136 TI - [Pulmonary and systemic hemodynamic changes and gas exchange in thromboembolic pulmonary vascular disease]. PMID- 2595137 TI - [Deep venous thrombosis]. PMID- 2595138 TI - [Future prospects in pulmonary artery thromboembolism]. PMID- 2595139 TI - [Variability of respiratory function variables in healthy aged men]. AB - We studied six healthy young males (young group; mean age 30.0 +/- SD 1.8 years, FVC 4.5 +/- 80.45 l and FEV1.0/FVC 87.6 +/- 4.3%), and five aged healthy males (aged group; age 63.8 +/- 3.0 years, FVC 3.40 +/- 0.22 l and FEV1.0/FVC 75.9 +/- 3.2%) to evaluate the variability of pulmonary function. We measured flow-volume curves, closing volumes, functional residual capacities (FRC) and airway resistances (Raw) five times in different days in each person. The coefficients of variation in FVC and FEV1.0 in both groups were less than 5%, and there were no significant differences in these coefficients between the two groups. Although the coefficients in FEV1.0/FVC in both group were less than 5%, there was a significant difference between the two groups. The coefficients in flow at 50% FVC (V50), maximal midexpiratory flow (MMF) and peak expiratory flow rate (PEFR) in the aged group were significantly larger than those in the young group. The coefficients in closing volume, FRC, Raw and specific airway conductance (SGaw) using body plethysmography exceeded 10% in both groups, and the coefficients in Raw and SGaw in the aged group were significantly larger than those in the young group. These results suggest that aging worsens the variabilities of respiratory function in FEV1.0/FVC, MMF, V50, Raw and SGaw. PMID- 2595140 TI - [Hemodynamic study of negative pressure ventilation using diaphragm pacing]. AB - A negative pressure ventilation (NPV) by unilateral or bilateral diaphragm pacing (DP) was prepared for canine experiments. A shift from positive pressure ventilation (PPV) to NPV resulted in elevation of mean aortic pressure, increase in stroke volume and depression of mean pulmonary arterial pressure. Examination of the interaction between respiratory cycle and cardiac function during PPV, disclosed a reduction of right ventricular stroke volume and elevation of mean aortic and right ventricular end-diastolic pressure at end inspiration, compared to those at end expiration. During NPV with DP, left ventricular stroke volume, heart rate and mean aortic pressure were increased immediately after DP (immediately after inspiration) compared to those at end expiration. The experimental model of DP, in which respiratory condition could be easily altered, was considered to be useful to evaluate the effect of NPV on cardiac function. PMID- 2595141 TI - [Left ventricular volume characteristics and its relationship with right ventricle after repair of tetralogy of Fallot]. AB - In order to study the left ventricular volume characteristics and right ventricular influence on left ventricle, cardiac catheterization and biplane cineangiography was performed in 61 patients after repair of tetralogy of Fallot. Preoperative left ventricular volume size was also measured in 25 patients. Postoperative left ventricular end-diastolic volume index (LVEDVI) was 93 +/- 22 ml/m2 (mean +/- standard deviation) and it was 140 +/- 29% of normal left ventricular volume. Left ventricular ejection fraction (LVEF) was 60 +/- 6%. Left ventricular size significantly increased from 109 +/- 25% to 140 +/- 23% of normal by corrective surgery (p less than 0.001). Left ventricular volume characteristics are correlated with right ventricle. LVEDVI increased with increasing right ventricular end-diastolic volume index (RVEDVI) and decreased right ventricular ejection fraction (RVEF). LVEDVI (ml/m2) = 60 + 0.29 RVEDVI (ml/m2), r = 0.52, p less than 0.001, LVEDVI (ml/m2) = 141 - 0.90 RVEF (%), r = 0.30, p less than 0.02. LVEF decreased with increasing RVEDVI and decreased RVEF. LVEF (%) = 68 - 0.075 RVEDVI (ml/m2), r = -0.51, p less than 0.001, LVEF (%) = 43 + 0.32 RVEF (%), r = 0.40, p less than 0.001. On the contrary there was no relationship between right ventricular volume characteristics and right ventricular systolic pressure. There were two cases whose LVEF was less than 50%. In one case right ventricular systolic pressure was as high as 98 mmHg. In the other patient RVEDVI was 299 ml/m2 (453% of normal right ventricular volume) because of severe pulmonary regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2595142 TI - [Significance of right precordial ST elevation in experimental right ventricular infarction]. AB - We produced experimental isolated right ventricular infarction (RVI) with closed chest method, and examined ECG changes of right precordial leads and changes of cardiac output (C. O) in 19 dogs. As a result, ECG showed ST depressions in leads, II, III, aVF and V2-V6 and ST elevations in a VR lead in all 15 cases of the proximal occlusion of right coronary artery (RCA). In 10 of 15 dogs ST elevations in some right precordial leads occurred, and the sensitivity of ST elevation in single right precordial lead was 60% (V5R), 53% (V4R) and 47% (V3R and V1), respectively for the detection of RVI. When left circumflex artery (LCX) was occluded, ST elevation in V4R lead after RCA occlusion was blocked. Therefore, it is thought that the sensitivity of ST elevation in right precordial lead may be lower than expectation in identifying RVI. Concerning anterior chest leads, none of 15 dogs with RVI showed ST elevations in leads V2-V6 in this study. If ST elevations in right precordial leads did not appear, variation of C.O was small and C.O reduced in proportion to the extension of ST elevations in right precordial leads. PMID- 2595143 TI - Update on tuberculosis. PMID- 2595144 TI - Update in tuberculosis: an overview. PMID- 2595145 TI - Progression of renal disease. PMID- 2595146 TI - Studies of therapy of progressive renal failure in humans. PMID- 2595147 TI - Self-reports of differentiation of self and marital compatibility as related to family functioning in the third and fourth stages of the family life cycle. AB - Using Bowen's, Olson's, and general systems frameworks, this investigator tested relationships among individual, marital, and family functioning in the stressed childrearing stages of the family life cycle. Sixty volunteer married couples completed the Level of Differentiation of Self Scale (LDSS), Locke-Wallace Marital Adjustment Test (MAT), and Family Adaptability and Cohesion Evaluation Scales (FACES) III. A significant canonical correlation was found among differentiation of self and marital compatibility as they both relate to family functioning. Subsequent canonical correlations were significant for wives but not for husbands, indicating gender differences in relationships among perceived individual, marital, and family phenomena. The concept of adaptability as proposed by Olson's Circumplex Model of Marital and Family Functioning was not supported. A revised model is proposed. PMID- 2595148 TI - Recovery: a phenomenon extending beyond discharge. AB - The purpose of this study was to conceptualize and order theoretically the process of recovery. Intensive telephone interviews were carried out at 2, 4, and 6 weeks postoperatively to elicit descriptions of postdischarge experiences from 25 subjects who had experienced uncomplicated hospitalizations for cholecystectomy surgery. Postdischarge recovery was a process of returning to normal as defined by preillness comparative standards of physical, social, and psychological well-being that progressed sequentially in three phases: passivity, activity resumption, and stabilization. Decisions concerning phase progression were made by integrating physiological and health professional cues with self imposed and situational pressures. Subjects who perceived negative physical symptoms, especially fatigue, and who were unable to respond to pressures expressed frustration with the recovery process. Implications for nursing practice include providing patients with individualized anticipatory guidance and interventions that build endurance. PMID- 2595149 TI - Infant care self-efficacy. AB - As attention in health care turns to prevention and health promotion, identification of populations at risk for avoiding care becomes increasingly important. The Infant Care Survey (ICS) is a scale to assess self-efficacy expectations for infant care tasks. Reliability and validity estimates for the ICS are supportive. Descriptions of content, factorial, and construct validation are given. Finally, ongoing research is described, and suggestions for use of the ICS are offered. PMID- 2595150 TI - [Reliability of scintigraphic methods in the diagnosis of coronary insufficiency]. AB - Some conceptual problems arise when applying the probability analysis to the scintigraphic diagnosis of coronary artery disease. Analysis with Bayes' rule considers disease to be present or absent, radionuclide test response to be positive or negative, sensitivity and specificity to be the same in all patients. In fact, disease can be graded in severity; test results can be analysed as continuous variables; sensitivity and specificity of our diagnostic procedures are not constants but depend of the population features. Moreover, the accuracy of the radionuclide tests refers to the coronary arteriogram, which is not the appropriate standard of coronary artery disease. PMID- 2595152 TI - [What is your diagnosis? Still's disease]. PMID- 2595151 TI - [The diagnosis of isolated long-term fevers: a reevaluation]. PMID- 2595153 TI - [Indications for tonsillectomy]. PMID- 2595154 TI - [Acute organic psychoses in the hospital. I. Clinical and differential diagnosis]. AB - In the general hospital, some patients may exhibit major mental disturbances secondary to a physical disorder. Early diagnosis of the organic etiology of these psychiatric disorders is essential, since the sooner an etiological treatment is applied, the better is the prognosis. In most cases, these psychiatric organic disorders should be treated in the general hospital. The article intends to make the non-psychiatric physician more familiar with the diagnosis of acute psychoses, especially in helping him to distinguish the organic from the 'functional' psychoses. PMID- 2595155 TI - [Experiences with the mini-external fixator used on the forefoot in complicated pressure necrosis]. AB - Purulent osteomyelitis in the foot region, accompanied by peripheral polyneuropathy, represents a grave complication after initially insufficient treatment of soft-tissue infections. The possible use and advantages of the external minifixator as an alternative to immediate primary forefoot or foot amputation are described. Initial results of personal observations are described. PMID- 2595156 TI - [A case from practice (155). "Mini"-adrenogenital syndrome, euthyroid goiter II, obesity]. PMID- 2595157 TI - [What is your diagnosis?]. PMID- 2595158 TI - [Current concepts of the pathogenesis of atherosclerosis]. AB - Rupture of plaques followed by thrombosis and thrombo- or atheroembolism mark the clinical horizon of ischemic organ lesions in atherosclerosis. Initiation and development of lesions precede these often dramatic events by decades. Precursor lesions arise within the first, irreversible ones may develop from the second decade of life onwards. Two concurring or succeeding pathogenetic mechanisms dominate: 1. Discrete or functional endothelial injury (in conjunction with hemodynamic wall stresses and effects of endogenous or exogenous toxic factors such as hormones, immune- and other mediators, components of tobacco smoke, etc.) induces increased flow of low density lipoprotein (LDL) into arterial tissue. Immigrating monocytes capture LDL and accumulate its cholesterol as ester droplets becoming foam cells. Net flux and accumulation of cholesterol probably correlate with plasmatic LDL-cholesterol levels. 2. Endothelial denudation, also occurring under the influence of mechanical wall stresses and in particular over precursor lesions, incites platelet aggregation and clotting mechanisms. As a consequence, arterial smooth muscle proliferates in the sense of repair of injury, resulting in the formation of scar tissue. Lipid-rich lesions with scanty scars seem to be particularly prone to rupture and thus important complications. Plaque rupture is probably the most common complication leading to ischemic disease, whereby the extent of formation and organisation of thrombi might determine whether infarction or chronic ischemia is the outcome. PMID- 2595159 TI - [The prevention of atherosclerosis]. AB - Factors indicative of an increased risk for atherosclerotic disease comprise hereditary factors, male sex, abuse of tobacco, elevated total and LDL cholesterol, hypertension, obesity and diabetes. Effective prevention is possible along two strategies: 1. population-oriented, using guidelines for life style, and 2. individual-oriented by identifying and treating those at significant risk. Changes in life style like to dispense with smoking, dieting and reducing cholesterol intake have to be tried before pharmacotherapy is attempted. Preventive measures should be encouraged as early as possible, ideally as health conscience education of children. Efficient drugs are available but not very cost efficient. They are useful as adjunct in selected cases. PMID- 2595161 TI - [Menopause and hormone therapy]. PMID- 2595160 TI - [Fatigue and lassitude]. PMID- 2595162 TI - [The treatment of drug addicts: experiences with group therapy]. PMID- 2595163 TI - [Various psychological factors of recovery]. PMID- 2595164 TI - [The cost of nutrition and its effect on human behavior]. PMID- 2595165 TI - [Emergency procedures by the practitioner facing psychiatric emergencies]. PMID- 2595166 TI - New immunobiologic approaches to the control of cancer. PMID- 2595168 TI - [Long term survival after basilar artery occlusion. 4 cases]. AB - Four cases of basilar artery occlusion with a follow-up from 7 to 12 years are reported. The first patient, a 60 year old woman, had a proximal occlusion which was revealed by an acute brain stem ischemia. The second case was a 63 year old man with an aortic aneurysm who had a single episode of vertebro-basilar insufficiency. Cerebral angiography demonstrated a lower basilar artery occlusion. The third patient, a 60 year-old woman, had been operated from right carotid artery and left vertebral artery stenosis; 8 years later, without clinical manifestations, a left carotid artery stenosis and an occlusion of the lower part of the basilar artery were discovered. The evolution was eventless after a left carotid endarterectomy. The last case was a 60 year old man who had a lower basilar artery occlusion associated with a left internal carotid occlusion. There was a full recovery after a hemiplegic stroke. From our personal cases and the review of the literature, long term survival after basilar artery occlusion may occur in occlusions restricted to the lower or middle part of the basilar artery and with a good collateral supply from carotid and cerebellar arteries. PMID- 2595167 TI - [The value of motor evoked potentials in the localization of radicular lesions. 2 cases of herniated cervical disc]. AB - Cervical electrical stimulation evokes a potential in the muscle innervated by the cervical and brachial plexuses. We present 2 cases of herniated cervical intervertebral disc which illustrate the usefulness of motor stimulation to localize a motor radicular lesion. The simultaneous recording of several muscles innervated by different radicular levels has enabled us to demonstrate the exact level and side of the lesion. Cervical motor tract stimulation is a good means of diagnosing a radicular lesion when peripheral nerve conduction velocities are normal. PMID- 2595169 TI - [Motor impersistance of the eyelids. Study of 93 cases and a discussion of pathogenic mechanisms]. AB - In a prospective study, 252 subjects were investigated for motor impersistence of the eyelids (MIE) by means of a protocol that evaluated its intensity and detected associated signs, notably other phenomena of motor impersistence. MIE was frequent, being found in 93 subjects. It was usually observed in diffuse brain lesions, then in lesions of the right hemisphere, particularly in the posterior and deep cortex. In right hemisphere lesions, MIE was significantly associated with constructional apraxia, visual neglect and Anton-Babinski syndrome. In diffuse cerebral lesions, MIE was accompanied by other phenomena of motor impersistence on a background of dementia. In these cases the P 300 wave latency was significantly prolonged. Three main mechanisms may be regarded as responsible for the occurrence of MIE: apraxia, disturbance of the interhemispheric balance (notably in lesions of the right hemisphere) and disorders of attention (predominant in diffuse lesions). Actually, in every case MIE should be inserted in a continuum the extremities of which are represented by the above mentioned mechanisms. PMID- 2595170 TI - [Giant thrombosed aneurysm of the left vertebral artery developing in the fourth ventricle]. AB - A case of giant, thrombosed, non haemorrhagic aneurysm of the distal portion of the left vertebral artery is reported. The patient came to medical attention with an acute cervical pain after a minimal cervical traumatism and a diagnosis of torticollis from rheumatologic cause was made. In fact, a few weeks before, he had suffered three episodes of right homonymous hemianopsia. Subsequently, hiccup, vomiting, orthostatic dizziness with postural hypotension appeared, suggesting a medullary lesion. CT scan showed a round, heterogeneous high-density lesion near the fourth ventricle. Angiography was normal. MRI showed an oval mass in the fourth ventricle, between the medulla and the cerebellum. Surgery found an aneurysm of the end of the left vertebral artery. PMID- 2595171 TI - [Bilateral diaphragmatic paralysis: sequelae of neuralgic amyotrophy]. AB - Diaphragmatic paralysis is rare in neuralgic amyotrophy. Total quick recovery is usual. We report a case with a diaphragmatic paralysis still present more than 30 years after the onset of a bilateral and recurrent neuralgic amyotrophy. Neuralgic amyotrophy should be considered as a possible cause of chronic diaphragmatic paralysis. PMID- 2595172 TI - Automobile accidents in patients with sleep disorders. AB - Sleep-related motor vehicle accidents are a serious safety hazard both for the driver who falls asleep and for others on the road. Sleep disorders may be significant contributing factor in some of these accidents. We reviewed data on sleep-related accidents from 70 control subjects and 424 adults with four categories of sleep disorders: sleep apnea, narcolepsy, other disorders of excessive sleepiness, and sleep disorders without excessive sleepiness. The proportion of individuals with sleep-related accidents was 1.5-4 times greater in the hypersomnolent patient groups than in the control group. In patients with hypersomnia, the incidence of sleep-related accidents per year of excessive sleepiness was 3-7%. Although the proportion of patients with sleep-related accidents was highest in narcoleptics, apneics were involved in more sleep related accidents because of their greater number. Apneics and nacroleptics accounted for 71% of all sleep-related accidents. The proportion of severe apneics who had sleep-related accidents was almost twice that of patients with mild or moderate apnea. Mean sleep latency by Multiple Sleep Latency Test did not differ significantly in patients with accidents and those without. Patients with a wide variety of sleep disorders appear to be at increased risk for sleep related accidents. The severity and duration of hypersomnia are probably not the only factors that contribute to that risk. These findings have implications for the management of patients with sleep disorders. PMID- 2595173 TI - Sex differences in the sleep EEG of young adults: visual scoring and spectral analysis. AB - Baseline sleep of 13 men (mean age of 23.5 years) and 15 women (21.9 years) was analyzed. Visual scoring of the electroencephalograms (EEGs) revealed no significant differences between the sexes in the amounts of slow-wave sleep and rapid-eye-movement (REM) sleep. Spectral analysis, however, detected significantly higher power densities during non-REM sleep over a wide frequency range (0.25-11.0 Hz) in the female versus male subjects. Also, during REM sleep, power densities were higher in the females. Analysis of the time course of EEG power density during sleep revealed that the differences between males and females persisted throughout the sleep episode. Comparison of these differences with published data on the effects of sleep deprivation on EEG power spectra did not suggest a common mechanism underlying sleep deprivation effects and the sex difference in sleep EEGs. It is concluded that sex differences in EEG power spectra are not likely to be caused by sex differences in sleep regulatory mechanisms but may, for instance, be caused by sex differences in skull characteristics. PMID- 2595174 TI - Decrease in delta sleep in growth hormone deficiency assessed by a new power spectrum analysis. AB - Seven pituitary dwarfs between 18 and 28 years old with congenital absence of growth hormone, i.e., isolated growth hormone deficiency (IGHD), were examined with polysomnography. Power spectrum analyses of the delta band showed a significant decrease in power in the delta sleep in the IGHD patients compared with the controls. Power spectrum analyses add a new dimension to the description of sleep, as it evaluates, not only frequency of the electroencephalogram (EEG) in time but also the amplitude of the EEG signal. This means that sleep of same quantity can have different powers; for example, 15 min of stage 4 in one person can have another quality than 15 min of stage 4 in another person. An additional observation was that the power in the delta band in the normal young controls showed a correlation to age, with significant decrease within a 10-year period. PMID- 2595175 TI - Twenty-four-hour structure of sleepiness in morning and evening persons investigated by ultrashort sleep-wake cycle. AB - "Morning" and "evening" persons, defined according to a modified version of the Horne and Ostberg questionnaire, performed the 7/13 min sleep-waking schedule under attempting sleep condition after sleeping for one night in the laboratory, and under the resisting sleep condition after one night of sleep deprivation. Morning types slept significantly more under the attempting sleep condition and showed an earlier rise in nocturnal sleepiness. After sleep deprivation, morning types had a more distinct sleep propensity pattern with well-defined midafternoon and nocturnal sleep gates. In this condition there was a significant interaction between type and time of day with respect to amount of sleep: morning types slept more during the night, and evening types slept more during the day. Based on their amounts of sleep, subjects were also divided into "sleepy" and "alert" types, which were independent from the chronotypology. PMID- 2595176 TI - Gender differences in the circadian temperature rhythms of healthy elderly subjects: relationships to sleep quality. AB - Body core temperature and subjective sleep quality were measured in 22 healthy elderly men and women while they lived at home and continued their normal daily activities. The acrophase of body temperature was phase-advanced by an average of 1.25 h in the older women compared to the age-matched men. Habitual bedtimes did not differ between men and women, but usual wakeup time and average sleep duration did: women awakened earlier and slept for shorter durations. Women were also less satisfied with their sleep than were the men. For the group, the acrophase of body temperature was significantly positively correlated with habitual bedtime and wakeup time. These data support the notion that age-related changes in the circadian timing system are, in large part, gender-dependent. The findings are also consistent with the hypothesis that alterations in sleep timing and quality that typically accompany aging are closely tied to age-related changes in circadian physiology. PMID- 2595177 TI - Interrater reliability of computer-assisted scoring of breathing during sleep. AB - Twenty-six records of sleep and breathing obtained with a portable monitoring system from elderly subjects were scored by three raters with computer assistance to examine interrater reliability of scoring. Raters were a medical student, a nurse practitioner, and a family physician, all of whom had at least one month's experience with the equipment. Agreement among raters was measured with the unweighted kappa statistic. Significant agreement was observed for all variables, although agreement was better for variables describing breathing (range of kappa 0.71-0.87) than for those describing sleep (range of kappa 0.34-0.57). Complete agreement among the three raters on diagnostic classification occurred in 17 cases. In the remaining 9 cases, 2 raters agreed, whereas the third differed by not more than one category for type of disturbance (e.g., normal versus hypopnea, hypopnea versus apnea) or severity (e.g., mild versus moderate). There was only one disagreement among raters for the 9 subjects with severe respiratory disturbance. We conclude that interrater reliability of identifying and characterizing breathing disturbance during sleep as recorded by portable monitoring is high among trained raters using computer assistance. PMID- 2595178 TI - [Catherine Ganie or hands-on chemotherapy. Interview by Marie-Helene Manillier]. PMID- 2595179 TI - [Consultation for tobacco withdrawal]. PMID- 2595180 TI - [Infusion pumps]. PMID- 2595181 TI - [Asthma: a course for children]. PMID- 2595182 TI - [Functional asthenia: psychopathological aspects]. PMID- 2595183 TI - [Nurses in hospital establishments]. PMID- 2595184 TI - [Lead poisoning and the industrial environment]. PMID- 2595185 TI - [Non invasive examinations in pneumology]. PMID- 2595186 TI - [Liaison nursing report form]. PMID- 2595187 TI - [The nursing profession in France]. PMID- 2595189 TI - The pathophysiology of the floppy infant. PMID- 2595188 TI - The floppy infant syndrome. PMID- 2595190 TI - Genetic diseases in the etiology of the floppy infant. PMID- 2595191 TI - Therapy and rehabilitation of the floppy infant. PMID- 2595192 TI - Parenting a floppy infant. PMID- 2595193 TI - Breast cancer in Rhode Island. PMID- 2595194 TI - Xenotransplantation in immunosuppressed nude mice of human solid tumors and acute leukemias directly from patients or in vitro cell lines. AB - Athymic nude (nu/nu) mice are widely employed for the heterotransplantation of human tumor cell lines established in vitro and tumor cells directly grafted from patients. By contrast, hemopoietic malignancies have consistently proved difficult to transplant and well-characterized human leukemias suitable for studies in nude mice are scarce. We report here our experience with subcutaneous xenotransplantation of human neoplastic cells into nu/nu mice immunosuppressed through sublethal irradiation and splenectomy (SI-nu/nu) and with an additional injection of anti-Asialo-GM1 antibodies (SIA-nu/nu) in order to eliminate natural killer activity. Thirteen out of 16 continuous cell lines established in vitro from solid tumors and 7 out of 14 human tumors obtained from fragments of surgical specimens formed a progressively growing tumor in SI-nu/nu mice. Six out of 8 in vitro established human leukemic cell lines and 5 out of 18 neoplastic hematopoietic cells directly xenotransplanted from the patient grew SIA-nu/nu mice. When the membrane and chromosome markers of neoplastic cells that grew into the mice were evaluated, only marginal differences with those of the original tumors were found. In addition, when interfering factors alter the histological aspect of the primary tumor, xenotransplantation may also be of some help in histological diagnosis. By using SI- and SIA-nu/nu mice, it is thus possible to build up several new in vivo experimental systems with fresh human tumors that may be of value in studying the efficacy of differentiation factors and immunological maneuvers on the in vivo growth of human tumors. PMID- 2595196 TI - One-step purification by high-performance liquid chromatography of retinal S antigen. AB - A number of subsequent chromatographic techniques are commonly used, over a period of a few days, in order to obtain pure retinal S-antigen (S-Ag), a 50,000 dalton molecular weight protein with strong uveitopathogenic properties. A rapid high-performance liquid chromatographic technique employing a TSK-G3000 SWG gel filtration column is described for the purification of bovine S-Ag. This single chromatographic step produced S-Ag preparations of high purity and recovery when compared to the conventionally isolated S-Ag. PMID- 2595195 TI - Behavior of prealbumin in the acute phase of polymyalgia rheumatica treated with 6-methylprednisolone. AB - Serum levels of prealbumin, fibronectin, fibrinogen, alpha 1-acid glycoprotein, C reactive protein, immunoglobulins, and white blood cell count were prospectively studied in 33 patients affected by polymyalgia rheumatica during the first 45 days of treatment with 6-methylprednisolone. Almost all parameters considered, except for fibronectin and IgM, settled within the normal range fairly quickly, while prealbumin showed a specular course compared with the other reactants. This behavior reflected the improvement of clinical symptoms registered in all patients after steroid treatment. Finally, the genesis of the low baseline prealbumin levels found in polymyalgia rheumatica/giant cell arteritis and their behavior during treatment are discussed. PMID- 2595198 TI - [Primary care reform in Catalonia. A new role for nursing]. PMID- 2595197 TI - Correlation between DNA synthesis and glucosamine incorporation in human diploid fibroblasts stimulated by fibroblast growth factor and fetal calf serum. AB - A 20 and 80% decrease of 3H-glucosamine incorporation was observed in resting human fibroblasts stimulated with fibroblast growth factor (FGF) and fetal calf serum (FCS), respectively. The decrease occurred as early as 15 min after stimulation. Inversely, DNA synthesis was increased 1 and 5 fold and cell number was increased 2 and 2.5 fold 72h later. 3H-glucosamine was incorporated in cell membrane glycopeptides (GP). Extracted from control or from cells exposed to FGF or FCS, GP have the same molecular weight and identical chemical constitution. The decrease of 3H-glucosamine incorporation caused by FGF and FCS appears to be related to the competitive binding between glucosamine-FGF and glucosamine-FCS components to GP, which probably constitute cell membrane receptors. A decline of 3H-glucosamine incorporation caused by FCS seems to result from the binding to cell-surface receptors (i.e., GP) of a large number of FCS components. The results suggest a correlation between cell growth rate and the density of growth promoting molecules received by cells, since a large decrease of 3H-glucosamine incorporation corresponds to a high increase of DNA synthesis in cells exposed to FCS, which is a mixture of components with multiple effects. PMID- 2595199 TI - [The programmed home visit]. PMID- 2595200 TI - [Depression in childhood and adolescence]. PMID- 2595201 TI - [Cardiorespiratory arrest. The care system in a 3rd-level hospital]. PMID- 2595202 TI - [Presentation of the model of nursing care developed by Gotzone Mora]. PMID- 2595203 TI - [The contribution of nursing to the quality of life]. PMID- 2595204 TI - [Anthropometric technics. Their application]. PMID- 2595205 TI - [Dietary habits in hemodialysis]. PMID- 2595206 TI - [What is an autotransfuser?]. PMID- 2595207 TI - [Continuing education. 41. Subject: pediatric nursing. Topic: How to care for the nursing infant?]. PMID- 2595208 TI - [Incentives and the "3 Es"]. PMID- 2595209 TI - Sensory-motor conduction time in amyotrophic lateral sclerosis. AB - 19 ALS patients were submitted to motor evoked potentials (MEP) and F-wave from thenar muscles. Somatosensory evoked potentials (SEP) from median nerve were recorded as well in 16 patients. MEP were bilaterally absent in 4 patients (21%) and monolaterally absent in 6 patients (3.6%). Among patients with recordable waves, MEP and F-wave were significantly delayed. Their upper motor neuron conduction time was clearly abnormal only in one case. In SEP recordings the N9 N13 was significantly delayed, but the N13-N20 was normal. Four patients showed a combined sensory-motor dysfunction (increase of both N19-N13 interval and F-wave latency). PMID- 2595211 TI - [Relationship between periodic movements in sleep and vigilance: analysis of the role of circadian rhythms]. AB - Periodic movements during sleep (PMS) are discussed in relation to several hypotheses concerning their etiology and their possible nosographic classification. In particular the role of central and peripheral events able to determine PMS is emphasized. The possible existence of space-intensity-time (SIT) patterns responsible for the vigilance profiles and the state of activity of central and peripheral effectors is also discussed. Finally the authors examine the modulating role of GABA on the circadian system and a possible metabolic instability of the GABAergic neurons responsible for PMS. This hypothesis is confirmed by the usefulness of clonazepam to treat such disorders. PMID- 2595210 TI - [Cerebral toxoplasmosis in subjects with acquired immunodeficiency syndrome]. AB - Cerebral toxoplasmosis is the most common cause of focal CNS disease complicating AIDS and may afflict 10% to 33% of such patients. We present the clinical, neuroradiological and immunological findings in 5 cases with cerebral toxoplasmosis complicating the acquired immune deficiency syndrome. All patients had focal neurological signs and symptoms; CT scan findings included single or multiple lesions with ring contrast enhancement, mass effect and oedema. CSF analysis showed increased protein levels, decreased glucose levels and pleocytosis; CSF IgG antitoxoplasma antibodies were positive in 4 patients; serum IgG antitoxoplasma antibodies were positive in all patients, while IgM resulted always negative in serum and in CSF. After therapy, in 2 cases CT scans showed small areas of encephalomalacia replacing the abscesses. We think that non invasive techniques (CT scans, CSF and serum immunochemical tests) together with the finding of a favourable response to therapy may be useful for the diagnosis of cerebral toxoplasmosis, allowing to avoid invasive technique such as cerebral biopsy. PMID- 2595212 TI - [Evaluation of cerebral circulation in the presence of carotid vessel changes]. AB - The importance of transcranial Doppler sonography (TCD) use in the presence of extracranial carotid artery diseases (occlusions, stenosis, parietal irregularities) is discussed. The preliminary data, obtained from 25 patients and as many normal subjects, show a significant correlation in the two groups, between blood flow velocities in the middle (MCA) and anterior cerebral arteries (ACA). PMID- 2595213 TI - Macrophage and lymphocyte antibody-dependent cellular cytotoxicity in spontaneous leukemogenesis of AKR/J mice. AB - Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by peritoneal macrophages and splenic lymphocytes was studied in young (15 weeks) and old (45 +/- 5 weeks) preleukemic AKR/J mice and leukemic (55 +/- 5 weeks) AKR/J mice. This strain spontaneously develops a virally induced T cell leukemia-lymphoma between the ages of 32 and 48 weeks. The peritoneal macrophages from the AKR/J leukemic and old preleukemic mice showed an impaired ADCC when compared with their respective age and tumor-free BALB/c controls and with young preleukemic AKR/J mice. Young and old preleukemic AKR/J mice and their respective controls had similar ADCC values with respect to splenic lymphocytes, whereas an impaired ADCC was observed by the splenic cells from leukemic AKR/J mice. The possibility of using ADCC mediated by macrophages as a test to detect the onset of the leukemic process is discussed. PMID- 2595215 TI - [Participation of platelets in the progression of atherosclerosis]. AB - The role of platelets in the early steps of atherosclerogenesis is controversial, but it is well established that platelets play a prominent part in arterial thrombosis, the leading event in the progression of atherosclerosis. Ulceration of the plaque breaks the endothelial cover, and induces blood to interact with the deeper components of the lesion, which leads to adhesion, activation and aggregation of platelets at the intimal breach. The resulting clump of platelets becomes a thrombus by further platelet accumulation and the addition of fibrin (through the triggering of the coagulation cascade). The thrombus has three possible fates. 1. It can grow by addition of successive layers of platelet, fibrin, white and red blood cells, until it eventually occludes the arterial lumen, often provoking an ischaemic event (such as a myocardial infarction). 2. At any time of its growth, the thrombus can be dislodged in whole or in part to cause arterial embolism. 3. The thrombotic material may become overgrown by endothelium and incorporated into the intima, becoming part of the atherosclerotic lesion and strongly contributing to the increase of its sclerotic as well as atheromatous (lipid) mass. Although the mechanisms of ulceration remain unclear, the resulting platelet activation leads to mural thrombosis and greatly contributes to the progression and complications of atherosclerosis. Available antiplatelet agents interfere favourably with the atherosclerotic process, but more efficient drugs will be designed when we better understand the mechanisms of ulceration and the influences that modulate the growth and fate of arterial thrombi. PMID- 2595214 TI - Elevated serum tumour markers and systemic disease. PMID- 2595216 TI - [Role of platelets in atherosclerosis and arterial thrombosis]. AB - A thrombus is an abnormal manifestation of normal haemostasis occurring on the internal surface of the blood vessels. Endothelial injury is the first event which ultimately may result in arterial thrombosis. Platelets stick to subendothelial components, are activated and release a number of mediators which aggregate new platelets. Simultaneously, thrombin is generated on the platelet surface and enhances these phenomenons. Due to the high blood flow which avoids local thrombin accumulation, arterial thrombosis is mainly composed of platelets with a poor fibrin content. A mural arterial thrombosis may embolize, be incorporated in the vessel wall, or occlude the lumen of the artery. Platelets are involved in the development of atherosclerosis: severe thrombocytopenia or von Willebrand disease protect efficiently against experimental atherosclerosis; several clinical conditions known to increase cardiovascular diseases are also associated with an increased platelet aggregability; in contrast, polyunsaturated fatty acids decrease platelets aggregability and protect against vascular diseases. PMID- 2595218 TI - [Current status of the cochlear implant technic]. PMID- 2595217 TI - [Influence of diet and life habits on platelet functions]. AB - The measurement of platelet activation utilizes relatively complex and ill standardized tests which vary from one laboratory to another. A long-term diet rich in saturated fatty acids is associated with platelet hyperaggregability which is suppressed after dietary changes, with an increased intake of polyunsaturated fatty acids, especially linoleic acid. However, the linoleic acid intake must not be too high. It is advised to maintain the polyunsaturated/saturated fatty acid ratio at 0.6 to 1 in subjects that are apparently in good health. Both 20:5 n-3 and 22:6 n-3, the main n-3 fatty acids of marine fish oils, inhibit platelet aggregation, but they do it weakly and only after a high intake. On the other hand, both emotional stress and tobacco smoking induce platelet activation, while a physical exercise of moderate intensity seems to be beneficial. Finally, there is no evidence that oral contraceptives with low oestrogen content induce platelet aggregation in women who have no other risk factor of coronary artery disease. PMID- 2595219 TI - [Tobacco and health]. PMID- 2595220 TI - [Medical confidentiality and AIDS]. PMID- 2595221 TI - [Value of biological markers in the diagnosis and monitoring of cystadenocarcinoma]. AB - Among the various antigens described as biological markers of ovarian cancer, only one, CA 125, is of value in clinical practice. CA 125 is not specific to epithelial ovarian cancer, but it is associated with this tumour. CA 125 assays are useless in the early detection of tumours in asymptomatic patients, but they are helpful to monitor the clinical course of treated cystadenocarcinoma of the ovary since a rise in CA 125 level may be observed several months before clinical or radiological evidence of ovarian malignancy is obtained. Finally, CA 125 determination is important before second-look laparotomy. PMID- 2595222 TI - [Surgical treatment of ovarian cystadenocarcinoma]. AB - Ovarian cystadenocarcinoma should be dealt with by surgeons well-trained in abdominal and pelvis surgery. The initial laparotomy has a dual purpose: to determine the tumoral stage after detailed evaluation of the lesions, and to remove all or most of the tumoral tissue. This is easy in localized cancers, but difficult, or even impossible, in the majority of stage III cancers. Radical surgery of stage III cancers has not yet been proven to influence the long-term survival. When surgical evaluation and excision have been unsatisfactory at the first laparotomy, another operation through a midline incision is justified before initiating an adjuvant treatment. This "second look" laparotomy is the best way to evaluate a tumoral residue after chemotherapy. In the absence of effective second-line therapy, the operation does not seem to improve the patient's comfort or survival, and it should be reserved to second-line therapeutic trials. Similarly, the surgical treatment of occlusive lesions due to recurrent cancer does not seem to influence the patient's comfort or survival. PMID- 2595223 TI - [Adjuvant treatment of cystadenocarcinoma]. AB - Adjuvant therapy remains necessary for all ovarian cancers expanding outside the ovary, and should be adjusted to stage and persistent tumor burden. Many problems need precise answers. Although progresses have been made, results are still unsatisfactory. The need for multicentric studies and trials is utmost underlined. PMID- 2595224 TI - [Rare forms of ovarian tumor]. AB - The most frequent ovarian tumour is cancer of the superficial epithelial layer. Sex cord mesenchymal tumours, lipoid cell tumours, germ cell tumours, gonadoblastomas, non-specific soft tissue tumours and metastatic tumours are rare. All these tumours are dissimilar, but they can be distinguished from the common ovarian adenocarcinoma by certain characteristics. It is among these rare tumours that cancers with feminizing effect (granula and theca cell tumours) or masculinizing effects (lipoid cell tumours, androblastomas) can be found. These tumours often affect children or young subjects; they are more belatedly and more rarely bilateral and they raise the problem of the conservative treatment of ovarian and reproductive functions. Among them, granula cell tumours sometimes recur after a long period, dysgerminoma is radio-sensitive and of good prognosis, and the prognosis of non-seminoma tumours has been much improved by chemotherapy. Most metastatic tumours are consecutive to endometrial, mammary or gastrointestinal cancer, the latter being the usual origin of Krukenberg's tumour. PMID- 2595225 TI - [Arterial hypertension and chronic kidney failure: recent data]. PMID- 2595226 TI - [The 9th International Symposium on Intensive Care and Emergency Medicine. Brussels, March 21-24, 1989]. PMID- 2595227 TI - [Physiopathologic concept of the obesity symptom]. PMID- 2595228 TI - [Lesions of the acetabular rim. Clinical manifestations, therapeutic strategies and perspectives]. AB - Partial rupture of the acetabular rim have usually been described as accompanying traumatic or dysplasic dislocations of the hip. The five cases reported here are in favor of a specific pathology of this fibrocartilage as it is in the knee or the shoulder. Besides, the functional symptoms are not without reminding that of these two joints with sudden onset of cracks, jerks, blockings and even a real joint instability. The pain is never isolated, but may accompany other disorders. The cases were selected in order to evaluate the clinical manifestations and the therapeutic consequences of such a lesion according to the articular history. The diagnosis can only be confirmed with arthrography, which, in addition, permits to evaluate the size of the rim and the condition of the cartilage. The three patients who underwent surgery presented the lesions shown on arthrography. The problem lies in the possible arthrogenic potential of a tear, left in place because minimally disabling for the patient. PMID- 2595230 TI - [Serum osteocalcin in rheumatologic practice]. PMID- 2595231 TI - [Mechanical tendon disease of the anterior tibial muscle]. PMID- 2595229 TI - [The level of osteocalcin and bone mass in patients receiving anti-vitamin K agents]. PMID- 2595232 TI - [Periodic disease and ankylosing spondylarthritis. Familial association]. PMID- 2595233 TI - [The effect of estro-progesterones on the inflammatory episodes of hand arthroses. Apropos of a case]. PMID- 2595234 TI - [The value of nuclear magnetic resonance imaging in the diagnosis of infectious epidural inflammation. Apropos of a case]. PMID- 2595236 TI - [Pancytopenia during rheumatoid polyarthritis treated by low doses of methotrexate]. PMID- 2595235 TI - [Intra-observer variation in the measure of the internal femoral-tibial space in knee arthrosis]. PMID- 2595237 TI - [Tophus of the fingers: an exceptional manifestation of gout]. PMID- 2595238 TI - The increased proximal tubular reabsorption of sodium and water is maintained in long-term insulin-dependent diabetics with early nephropathy. AB - Proximal tubular reabsorption of sodium and water was investigated in long-term insulin-dependent diabetic patients with normoalbuminuria (group I, n = 19), microalbuminuria (group II, n = 39), diabetic nephropathy (group III, n = 12) and in 13 healthy age-matched subjects. Glomerular filtration rate was measured with the single injection, 51Cr-EDTA technique. The fluid flow rate out of the proximal tubules was assessed by the renal lithium clearance. Although glomerular filtration rate was significantly elevated in the diabetic patients (Group I: 122 +/- 16, Group II: 121 +/- 18, Group III: 110 +/- 17, CONTROLS: 105 +/- 13 ml/min X 1.73 m2), lithium clearance was similar in the four groups (Group I: 19 +/- 6, Group II: 22 +/- 7, Group III: 19 +/- 5, CONTROLS: 23 +/- 4 ml/min X 1.73 m2). Both absolute and fractional proximal reabsorption of sodium and water was enhanced in diabetes. Indices of distal tubular function did not differ between controls and patients with insulin-dependent diabetes. Sodium clearance was about the same in the four groups. Our study suggests that the enhanced proximal reabsorption of sodium and water in insulin-dependent diabetic patients is still observed despite the presence of incipient or overt diabetic nephropathy. PMID- 2595239 TI - A new enzyme-linked immunosorbent assay for urine and serum concentrations of the carboxyterminal domain (NCl) of collagen. IV. Application in type I (insulin dependent) diabetes. AB - The major collagenous component of glomerular basement membrane (GBM) is collagen IV. Serum concentrations of the carboxyterminal end (NCl) of collagen IV have been proposed to be related to GBM turnover, which has been suspected to increase in diabetes mellitus. For the quantification of serum and urinary concentrations of NCl, a specific, sensitive enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies was developed. The detection limit of the assay was 30 micrograms/l at the 50% intercept of the standard curve. The intra- and interassay coefficients of variation were 6.2% and 13.9% for serum, respectively, and 11.9% and 39.7% for urine, respectively. The levels of NCl in serum and urine in 67 insulin-dependent diabetics and in 90 sex- and age-matched controls were compared. There were no differences in the serum concentrations of NCl between the diabetics and healthy controls. As a group, the diabetics had a higher urinary excretion of NCl than the controls (20.1 vs 12.5 ng/min, 2p less than 0.05). Furthermore, the results showed that the excretion of NCl in the urine was normal when the urinary albumin excretion rate (AER) was normal (less than 6.5 micrograms/min). The excretion was increased during the early stage of incipient diabetic nephropathy (AER 6.5-30 micrograms/min) and decreased to normal values with progression to clinical diabetic nephropathy (AER above 500 micrograms/min). Thus, it is suggested that an increased urinary excretion of NCl may be an early marker for incipient diabetic nephropathy. PMID- 2595240 TI - Comparison of two methods for the determination of the isoenzymes of alpha amylase in serum and urine. AB - In this paper we describe our results of the determination of the isoenzymes of alpha-amylase in serum and urine with two monoclonal antibodies, using 4,6 ethylidene-protected 4-nitrophenylmaltoheptaoside as substrate. For comparison we have used the wheat-germ inhibitor method with blue starch as substrate. The differences observed between each method were small. The technique using monoclonal antibodies is easy and reliable and can, therefore, replace the wheat germ inhibitor method. PMID- 2595241 TI - Determination of homocysteine in plasma by ion-exchange chromatography. AB - A rapid ion-exchange chromatographic method for determination of total homocysteine in plasma is presented. The method has a coefficient of variation of approximately 5%. A comparison with a slower method previously used in our laboratory showed a high correlation (r = 0.993). The risk of oxidation of homocysteine during the chromatography and the necessary level of dithiotreithol to prevent oxidation are also established. PMID- 2595242 TI - Effects of erythrocytes, bicarbonate, temperature and albumin on in vitro ionized calcium variations with pH. AB - Using a heart lung machine as an in vitro model, the relation between ionized calcium (cCa2+) and pH has been shown to depend on several variables such as erythrocytes, temperature and albumin as well as the total calcium and bicarbonate concentrations. The respiratory acid-base disturbances were simulated by changing the gas flow between 1.0 and 2.41 min-1 by adding CO2, to the machine at a concentration of 0 to 17%. When pCO2 was used to alter pH, cCa2+ varied from 0.16 mmol l-1 per pH unit to 0.52 mmol l-1. The regression slope of cCa2+ on pH was made steeper by decreasing erythrocyte volume fraction and by increasing temperature and the concentrations of HCO3, calcium or albumin. The metabolic acid-base alterations were produced by HCl or NaHCO3 at a constant gas flow, cCA2+ changes per pH unit were 0.70 mmol l-1 in plasma and 1.04 mmol l-1 in whole blood. The different results found in plasma and in erythrocyte fluids may be explained by their different buffering capacity. Haemoglobin may buffer hydrogen ions, and the formation of HCO3- is catalysed by carbonic anhydrase from the red cells. PMID- 2595243 TI - Performance of dry-chemistry instruments in primary health care. AB - The results from an external quality control of dry-chemistry instruments are presented. The performance with regard to imprecision was good. With regard to accuracy, the performance was poor for aspartate aminotransferase, creatine kinase, lactate dehydrogenase, triglycerides and uric acid. The inaccuracy of alanine aminotransferase, bilirubin, cholesterol, creatinine, glucose and potassium was comparable to that obtained by hospital instruments using wet chemistry. There were no large differences with respect to quality between Seralyzer and Reflotron. However, Seralyzer users performed more analyses per week, analysed a higher number of constituents and had more experienced operators than the Reflotron users. Reflotron users more often analysed the sample in connection with the consultation. The importance of an established quality control programme for these instruments is underlined. PMID- 2595244 TI - Clinical application of sodium-23 nuclear magnetic resonance for measurement of red cell sodium concentrations. AB - Red cell sodium (RBC-Na+) concentrations were measured using 23Na nuclear magnetic resonance (NMR), without the destruction of erythrocyte membranes. Subjects were categorized into four groups: 20 normotensive subjects (NT group), 20 age-matched essential hypertensive patients (EHT group), 10 patients with primary aldosteronism (PA group), and 18 patients treated with digoxin (DIG group). Although RBC-Na+ concentrations were similar between the NT group (6.14 +/- 0.80 (Mean +/- SD) mmol/l) and the EHT group (5.92 +/- 0.99), they were significantly higher in both the PA group (7.55 +/- 0.88, p less than 0.001) and the DIG group (8.43 +/- 3.81, p less than 0.02). In the PA group, RBC-Na+ concentrations decreased significantly after resection of the adenoma, and there was an inverse relationship between serum potassium and RBC-Na+ concentrations (r = -0.65, p less than 0.01). In the DIG group, RBC-Na+ concentrations tended to increase in proportion to serum digoxin levels (r = 0.53, p less than 0.05). These results support the view that RBC-Na+ concentrations are determined primarily by Na+/K+-pump activity of red cell membranes. This study showed also that Na+ NMR is an useful method determining intracellular Na+ concentrations. PMID- 2595245 TI - Effect of haem arginate on colony formation by haematopoietic progenitors in vitro. AB - The effect of haem arginate, a new stable haem compound, was studied on colony formation by erythroid (CFU-E, BFU-E) and granulocyte-macrophage (CFU-GM) progenitors from the bone marrow of 12 healthy persons. At the concentration of 10 mumol/l haem arginate significantly (p less than 0.05) increased and at the concentration of 200 mumol/l significantly decreased (p less than 0.005) the colony formation of CFU-E. A similar, though not significant, trend was seen in the BFU-E colony growth, while the CFU-GM colony formation was not influenced at any concentration between 1 and 200 mumol/l. We conclude that the stimulation of erythropoiesis in vitro is seen at lower concentrations with haem arginate than with former haemin preparations. PMID- 2595246 TI - Characterization of the silicone tonometer using a membrane-covered transcutaneous electrode. AB - A new oxygen tonometry system consisting of a silicone tube, highly permeable to O2 and CO2 is described. The silicone tube was connected to a membrane-covered transcutaneous oxygen electrode (E5242 Radiometer A/S, Copenhagen, Denmark) via an airtight polycarbonate chamber, and flushed with isotonic saline equilibrated with atmospheric air. The present tonometer system offers certain advantages compared with other systems: continuous reading, minimal oxygen consumption, furthermore the system is thermostated and is insensitive to movement. The tonometry system was tested in vitro for characterization of a silicone tube (Coroplast, Fritz Muller KG, Wuppertal, FRG) 1.0 mm in inner diameter and 1.5 mm in outer diameter. The experiments showed that the oxygen tension measured at the electrode after passage of the tonometer approached the oxygen tension outside the tonometer when the length of the tonometer was increased and when the flushing rate of saline through the tonometer was decreased. The time taken for the flushing solution to reach an equilibrium with the oxygen tension outside the tonometer increased with increasing tonometer length, and decreased with increasing flushing rate. Changing the difference between oxygen partial pressure in the flushing solution and the oxygen partial pressure outside the tonometer tube did not influence the relative equilibration value and the equilibration time. When a pO2 value is measured by the electrode, the exact oxygen tension outside the tonometer tube, for every given length of the tonometer and flushing rate through the tonometer can be read from our calibration curves. PMID- 2595247 TI - Cobalamin and its binding protein in rat milk. AB - Cobalamin and its binding protein, haptocorrin, are present in rat milk throughout the lactation period. The concentration of cobalamin is approximately 0.3-times the concentration of the unsaturated binding protein. The concentration of the unsaturated cobalamin-binding protein varies between 18 nmol l-1 and 16 nmol l-1. The binding protein has a Stokes radius of 2.49 nm when saturated with cobalamin and 2.61 nm when unsaturated. It binds cobalamin over a broad range of pH and is able to bind cobinamide also. With immunohistochemistry, we find haptocorrin immunoreactivity in the mammary glands and in the sebaceous glands of the nipple. PMID- 2595248 TI - Inadequate algorithm: a cause for 'incorrect pH 7.40 correction' in ionized calcium analysers. AB - As a preliminary step in a study of the effects of calcium ligands on the pH standardization of ionized calcium (Ca2+) measurements in blood, the slope of logCa2+ = f(pH) linear relationship characterizing the pH-sensitive calcium buffer capacity of the specimen was investigated in 12 serum pools on three different instruments. The pH 7.40 correction line should be horizontal. This was the case for the ICA-2 but not for the ICA-1 and the NOVA-8. The discrepancy was caused by an incorrect setting of the built-in slope correction factor in the ICA 2; coincidentally, its value was close to the effective slopes of the serum pools used in the study. Thus, the 'abnormal' behaviour of the ICA-1 and the NOVA-8 was caused by an inadequacy of the built-in algorithm to the characteristics of our serum pools. These findings lead us to reconsider the use of a fixed and constant correction factor to normalize actual ionized calcium values. PMID- 2595249 TI - Effects of heavy hyperventilation on transcutaneous and arterial oxygen tensions in healthy adults. AB - Transcutaneous pO2 on thorax and the volar part of the forearm was measured in six healthy volunteers during heavy hyperventilation, and the values compared with simultaneously measured arterial blood pO2. We found a significant rise in arterial pO2 during hyperventilation with a lesser increase in thoracic transcutaneous pO2. When measured on arm the transcutaneous pO2 did not even rise significantly. After hyperventilation pO2 fell to values below the resting level. The transcutaneous/arterial pO2 index, fell significantly during hyperventilation with the greatest reduction in the arm index. After hyperventilation the arm index returned to the control values, whereas the thoracic index remained low. We suggest, that the significant fall in transcutaneous/arterial blood pO2 index during hyperventilation is caused primarily by skin vasoconstriction, whereas the fall in pO2 after hyperventilation is caused by hypoxia. When measured on areas with increased muscular activity transcutaneous pO2 might depend on the local blood flow and skin oxygen consumption also, causing problems in interpretation with certain patient groups. PMID- 2595250 TI - The acute effect of acetazolamide on glomerular filtration rate and proximal tubular reabsorption of sodium and water in normal man. AB - The acute effects on kidney function of acetazolamide (250 mg) given intravenously were evaluated in seven healthy subjects. Glomerular filtration rate was measured as the renal clearance of 51Cr-EDTA, and fluid flow rate out of the proximal tubules was assessed by measurement of the renal lithium clearance. An 18% decline in glomerular filtration rate (ml/min) was observed after acetazolamide administration (109 +/- 16 vs 89 +/- 14, p less than 0.02), while lithium clearance (ml/min) increased by 35% (30 +/- 5 vs 38 +/- 8, p less than 0.02). Absolute proximal tubular reabsorption of water (ml/min) was reduced by about one third (79 +/- 12 vs 51 +/- 9, p less than 0.02), and fractional proximal reabsorption of water and sodium (%) declined (73 +/- 2 vs 58 +/- 6, p less than 0.02). Renal sodium clearance and absolute distal reabsorption of sodium increased, while fractional distal reabsorption of sodium declined. Acetazolamide reduces absolute and fractional proximal tubular reabsorption of sodium and water, and glomerular filtration rate. Primarily, this induces an increase in the output of fluid from the proximal tubules accounting for the diuretic effect of the drug. The acute fall in glomerular filtration rate is probably mediated by a temporary increase in proximal intratubular pressure and activation of the tubuloglomerular feedback mechanism. PMID- 2595251 TI - Comparison of ultracentrifugation and a precipitation method for high-density lipoprotein cholesterol quantitation in insulin-dependent diabetic patients. AB - We compared sodium phosphotungstic acid and magnesium chloride precipitation method for high-density lipoprotein (HDL) cholesterol quantitation with the ultracentrifugation method in 64 insulin-dependent diabetic patients with plasma triglyceride less than 3 mmol/l. The cholesterol content of HDL after precipitation of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was 86% +/- 3% of the cholesterol content of HDL (q greater than 1.063) determined after ultracentrifugation at q = 1.063 (1.33 +/- 0.05 mmol/l vs 1.55 +/- 0.06 mmol/l; p less than 0.001). HDL cholesterol determined after precipitation closely correlated to HDL cholesterol determined after ultracentrifugation (r = 0.97; p less than 0.001). The absolute difference between the HDL cholesterol values obtained by the two methods was correlated to HDL cholesterol (ultracentrifugation) (r = 0.75; p less than 0.001), but it was not correlated to VLDL cholesterol, LDL cholesterol, triglyceride, HbA1c, blood glucose or serum albumin. LDL cholesterol calculated by use of Friedewald's formula was 108% +/- 4% of the cholesterol content of LDL (q = 1.019 to 1.063), determined after ultracentrifugation, but the calculated and the ultracentrifugally determined LDL cholesterol values were closely correlated (r = 0.98; p less than 0.001). These results suggest that during sodium phosphotungstic acid and magnesium chloride precipitation of plasma from diabetic patients, a constant fraction of HDL cholesterol is co-precipitated, resulting in a systematic difference in HDL cholesterol quantitation when compared with the ultracentrifugation method. PMID- 2595252 TI - Improved recovery of cells elutriated from bronchoalveolar lavage fluid. PMID- 2595253 TI - Deranged gastric mucus secretion in erosive prepyloric changes. AB - Gastric mucus secretion was quantitatively and qualitatively assessed in 44 patients with endoscopic diagnosis of erosive prepyloric changes (EPC) grade 2 or 3. A matched group of patients with normal endoscopic appearance was used as a control group. The total amount of mucus glycoproteins in fasting gastric juice was similar in EPC patients and in healthy controls. However, the viscous and protective properties of mucus, as assessed by the ratio of neutral to total mucoproteins ('mucoprotective index') was significantly (p less than 0.01) reduced in patients with macroscopic erosions (grade 3 EPC). Alterations of the gastric mucous coating may account for the passive intraluminal outflow of HCO3 previously reported in subjects with grade 3 EPC. Whether the impairment of the 'mucus-bicarbonate' barrier is a cause or a consequence of prepyloric erosions remains to be determined. PMID- 2595254 TI - Gallstones and plasma lipids in a Danish population. AB - A cross-sectional study of gallstone disease, ascertained by ultrasonography, comprised 4581 men and women of Danish origin, aged 30, 40, 50, and 60 years, of whom 3608 (79%) attended the investigation. The prevalence was assessed in relation to plasma concentrations of total cholesterol, high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol, and triglyceride. In the univariate analysis gallstone disease was significantly associated with high triglyceride and low high-density-lipoprotein cholesterol. No significant association among gallstones and total cholesterol and low-density-lipoprotein cholesterol was seen. In multivariate analyses triglyceride lost its significant association with gallstone disease, whereas total cholesterol became negatively associated with gallstones. This was seen for both the high-density-lipoprotein and the low-density-lipoprotein fraction of cholesterol. The difficulties in analysing present plasma lipid status with gallstone prevalence must be stressed. Looking only at small gallstones, which could represent newly formed stones, a change from a negative to a positive association between gallstone and both low density-lipoprotein cholesterol and total cholesterol was seen. PMID- 2595255 TI - Contraction of canine stomach and small bowel by intravenous administration of serotonin. A physiologic response? AB - Serotonin is found in large quantities in the gastrointestinal tract, where it can increase gastrointestinal motility. Whether this response represents a physiologic event has not previously been shown. In our investigation eight conscious dogs were fitted with strain gauges to monitor motility responses to serotonin. When infused intravenously, serotonin significantly increased the contraction rate and force of canine stomach, small bowel, and isolated Thirty Vella loops. Whole blood serotonin levels monitored by radioimmunoassay showed no significant increase in levels during these infusions. Serotonin may have a physiologic function in the mediation of gastrointestinal motility. PMID- 2595256 TI - Serum gastrin in chronic renal failure: its relation to acid secretion, G-cell density, and upper gastrointestinal findings. AB - The interrelations among fasting serum gastrin, serum creatinine, gastric acid secretion variables, and G-cell densities were analyzed in 47 patients with chronic renal failure (CRF). The patients also underwent gastroscopy and radiologic upper gastrointestinal barium examination. It is suggested that the hypergastrinemia seen in CRF is related to several factors: gastric acidity, grade of renal failure, G-cell density, and basal gastrin secretion rate. With regard to serum gastrin two different populations can be found, the cutting-off point being 300 ng/l. Although the group with high gastrin levels included significantly more patients with gastric body atrophy than the other group (4 of 11 versus of 1 of 36), most of them had no atrophy, which indicates that (an)other mechanism(s) is responsible for the hypergastrinemia. In the relation between serum gastrin and gastric acidity also, two differently behaving subgroups emerged. In the first, strong acidity change corresponded to minor gastrin change, whereas in the other, minor acidity change corresponded to marked gastrin change. The correlation coefficients between gastrin and acidity were high within both subgroups. During regular dialysis patients preserve the characteristics delineated from non-dialyzed values. Patients with signs of duodenal ulcer disease had high maximal acid output and low serum gastrin. Otherwise no associations were found between GI findings and the variables studied. PMID- 2595257 TI - Sphincter of Oddi dysfunction. Dynamic cholescintigraphy and endoscopic retrograde cholangiopancreatography with papillotomy in diagnosis, treatment, and follow-up study. AB - The study compares dynamic cholescintigraphy with traditional methods in diagnosing sphincter of Oddi dysfunction. Five patients with dysfunction of the sphincter, in accordance with traditional diagnostic criteria, are compared with 25 patients with postcholecystectomy syndrome. Dynamic cholescintigraphy showed complete separation of the two groups, T1/2 distinguishing better than Tmax. The patients with sphincter dysfunction were treated with endoscopic papillotomy (EPT) for symptomatic relief. Three had early complications. At follow-up study the courses were uneventful. Their symptoms had disappeared or markedly improved, and dynamic cholescintigraphy was normalized. In conclusion, dynamic cholescintigraphy seems to be a reliable noninvasive method for identification and control of patients with sphincter of Oddi dysfunction suitable for treatment with EPT. PMID- 2595258 TI - The action of histamine on the isolated stomach muscle of the cat. AB - The effect of histamine on contractile and electric activity was studied in the isolated stomach muscle strips of 138 cats. Histamine dose-dependently produced tonic and phasic contractions of the muscle preparations from the fundus and the corpus but only phasic contraction of the antral muscle preparations. The frequency of gastric slow waves (SWs) was also increased dose-dependently by histamine. The responses of muscle contractions and gastric SW frequency to histamine were completely blocked by pretreatment with pyrilamine (10(-6) M) and were significantly inhibited by atropine (10(-5) M) but not by cimetidine (10(-5) M), hexamethonium (10(-5) M), phentolamine (10(-5) M), or propranolol (10(-5) M). The inhibition by pyrilamine was competitive. Although atropine inhibited the effect of histamine significantly, it could not completely block the effect of histamine even at a high concentration (3 x 10(-5) M). It is concluded that histamine may participate in the regulation of gastric motility in the cat by acting on the H1 receptor to cause the release of acetylcholine and also other contractile substance(s). PMID- 2595260 TI - Probable role of both sulfhydryls and prostaglandins in gastric mucosal protection induced by S-adenosylmethionine. AB - The role of both sulfhydryl groups and endogenous prostaglandins in the protective effect of S-adenosylmethionine against ethanol-induced gastric mucosal damage was studied in rats. Drugs were administered subcutaneously or intragastrically to fasted rats 30 or 60 min before 100% ethanol (1 ml/rat), and mucosal lesions were measured planimetrically 1 h later. The gastric mucosal protection given by S-adenosylmethionine or by 20% ethanol (adaptive protection) was significantly diminished by pretreatment of rats with the sulfhydryl blocker iodoacetamide or with the cyclooxygenase inhibitor indomethacin. The protective effect of S-adenosylmethionine could be totally abolished only by pretreatment with the combination of iodoacetamide and indomethacin. Our present data suggest that endogenous release of prostaglandins and sulfhydryl groups may play a role in the protective actions of both S-adenosylmethionine and 20% ethanol (adaptive protection) against ethanol-induced gastric mucosal damage. PMID- 2595259 TI - Postprandial gallbladder filling: relation to gastrointestinal motility. AB - A technique of combined hepatobiliary scintigraphy and gastrointestinal motility recordings was used to study the relationship between gallbladder dynamics and gastrointestinal motility recordings in the postprandial state in eight healthy male volunteers. In all, a fed-like motility pattern was observed after ingestion of a standard meal, and all activity from the HIDA-scintigraphy was diverted to the duodenum. Gallbladder radioactivity on the scintigram was not seen until 145 249 (median, 180) min after ingestion, except for two cases in which an early and transient activity was seen. Together with increasing gallbladder radioactivity characteristic changes in duodenal motility occurred. In five subjects a decrease in motility index was encountered with a motility curve resembling phase I of the interdigestive migrating motor complex. In one subject it was associated with the appearance of a phase-III complex, and in two subjects it occurred without any changes in motility index. PMID- 2595261 TI - Experimental chronic pancreatitis in the pig. AB - Chronic pancreatitis was induced in 22 piglets by dividing all pancreatic attachments to the duodenum; five sham-operated piglets served as controls. Two piglets died of postoperative complications. The animals were autopsied 2, 4, or 6 weeks postoperatively. All operated animals developed chronic pancreatitis. Concomitant with the development of interstitial fibrosis, an increasing progressive atrophy of the exocrine parenchyma occurred, with preservation of the islets of Langerhans. This atrophy and fibrosis were considerable already after 2 weeks. In one piglet only there was some acute inflammation and fat necrosis, whereas all showed at least moderate chronic inflammation, which did not change with time. The growth of the piglets stopped, and all had diarrhoea, which was thought to reflect exocrine insufficiency. Two animals (9%) developed a large pancreatic pseudocyst, and all animals had wide pancreatic ducts. The endocrine function was undisturbed. Intravenous glucose tolerance tests showed that the animals did not become diabetic. This model is appropriate for the study of experimental pancreatitis. PMID- 2595262 TI - Prognosis after the first episode of gastrointestinal bleeding or coma in cirrhosis. Survival and prognostic factors. AB - Hepatic encephalopathy and gastrointestinal (GI) bleeding are the most serious complications in cirrhosis. The purpose of this study was to examine survival after the first episode of GI bleeding or coma, or both, and to identify variables associated with the subsequent survival in 284 consecutive patients with cirrhosis admitted to one division of hepatology over a period of 81 months. Patients who only bled had markedly longer survival than those who only had coma, whereas those who had both bleeding and coma had by far the poorest survival, only 15% being alive 1 year later. Several other variables showed a significant association with survival. In a Cox multiple regression analysis the following four variables showed significant association with a short survival: coma and bleeding at the episode, ascites, low prothrombin index, and high serum creatinine. The prognostic index derived from the Cox model, which was validated by a split-sample testing technique, may be used to refine prognostic estimation in this subgroup of severely ill cirrhotic patients. PMID- 2595263 TI - Colorectal cancer prevention. In search of risk factors and increased effectiveness of surveillance programs. AB - The increasing incidence of colorectal cancer has emphasized the need for tools for the detection of polyps at risk of cancer or detection of malignant tumors in a more favorable stage. So far, no general prognostic risk factors are known which enable the diagnosis of cancer on the basis of simple tests or clinical symptoms. We know, however, that the prevalence of cancer and adenomas is age related, with the highest incidence between 65 and 80 years. This should enable us to perform endoscopic screening programs on selected age groups to detect the malignant lesions at an earlier stage or to prevent the development of malignancy by removal of large polyps. Such screening programs should be performed in a controlled manner, to verify the impact of endoscopy on the prognosis and incidence of colorectal cancer. Meanwhile, the endoscopic surveillance of polyp bearing patients will have to be conducted in accordance with the calculated risk of malignancy. Our increasing knowledge of risk factors in adenomas has, so far, allowed us to perform endoscopic controls of these patients less frequently than 10 years ago. For the future we hope to be able to select the high-risk individuals and adenomas for treatment, which in turn will enable us to ignore the majority of adenomas, which will definitely not undergo malignant transformation. PMID- 2595264 TI - Enzyme patterns and flow cytometric DNA measurements in colorectal hyperplastic polyps and tubular adenomas less than five millimeters. AB - Glucose-6-phosphate dehydrogenase (G6PD) activity, lactate dehydrogenase (LD) activity, and cytometric flow measurement of nuclear size and cell cycle distributions were registered in biopsy specimens from adenomas and hyperplastic polyps less than 5 mm. The G6PD and LD activities in adenomas, 36.8 +/- 4 U/g protein and 1580 +/- 163 U/g, respectively, were significantly higher than in hyperplastic polyps, 17.9 +/- 2.6 U/g and 1080 +/- 107 U/g, or in normal mucosa, 14.7 +/- 0.8 U/g and 1174 +/- 56 U/g, respectively. G6PD activity was significantly higher in adenomas with moderate (44 +/- 5.8 U/g) than in those with mild (32 +/- 5.9 U/g) dysplasia, in contrast to LD. No difference in enzyme activity was observed between hyperplastic polyps and normal mucosa. The growth of adenomas and hyperplastic polyps was not significantly different during the 2 years of follow-up study before biopsy specimens were taken. Increased nuclear size, unrelated to grade of dysplasia, was registered in 12 of 20 adenomas, in 1 of 10 hyperplastic polyps, and in 2 of 42 specimens from normal mucosa. Adenomas and normal mucosa from individuals with adenomas showed a significantly increased number of cells in S-phase. The values were 10.2 +/- 3% and 8.8 +/- 4%, respectively. Normal control value was 6.8 +/- 2.2%. An increased number of cells in G2-phase was observed only in adenomas (6.9 +/- 2.7% compared with 4.9 +/- 1% in controls). None of the adenomas showed aneuploidy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2595265 TI - Dissociation of changes in plasma cholesterol and hepatic cholesterol synthesis, assessed by precursors in bile, after jejunoileal bypass with 3:1 and 1:3 jejunoileal ratio. AB - Hepatic cholesterol synthesis, assessed by the biliary content of post-squalene cholesterol precursors relative to cholesterol, was related to fasting plasma cholesterol fractions in obese patients before (n = 7) and after jejunoileal bypass surgery with either a 3:1 ratio (n = 15) or a 1:3 ratio (n = 14) between jejunum and ileum left in function. The content of precursors increased after bypass surgery, and more so with a 3:1 than with a 1:3 jejunoileal ratio. However, the two types of bypass resulted in similar reductions in plasma concentrations of total cholesterol and low-density lipoprotein cholesterol. Within the unoperated group and the 3:1 bypass group the precursor content and plasma cholesterol levels were, as expected, inversely correlated, but within the 1:3 bypass group there were either weaker or even positive correlations. These findings suggest that the link between stimulation of hepatic cholesterol synthesis and reduction in plasma cholesterol may depend on the length of jejunum and ileum left in function. PMID- 2595266 TI - Gallbladder mucin and cholesterol and pigment gallstone formation in hamsters. AB - We measured gallbladder mucin production by hamsters fed diets lithogenic for either cholesterol or pigment gallstones. In hamsters on the cholesterol stone diet, gallbladder production of 3H-glucosamine-labeled mucin was elevated two- and seven-fold after 1 and 3 weeks, respectively. After 1 week cholesterol crystals were seen in a mucus gel on the gallbladder surface. In hamsters on the pigment stone diet, gallbladder mucin production was significantly elevated after 1 and 3 weeks. The first precipitation of pigment crystals was in mucus in bile or on the gallbladder surface. Black pigment stones grew by agglomeration of pigment crystals enmeshed in mucus. In conclusion, gallbladder mucin production is increased before cholesterol or pigment stone formation, and the earliest deposition of crystals is in mucus in bile or on the gallbladder surface. PMID- 2595267 TI - Topical treatment of ulcerative proctitis with lidocaine. AB - Rectal biopsy specimens from patients with ulcerative proctitis/proctosigmoiditis (UP/PS) were investigated immunocytochemically. In general, a changed mucosal innervation was demonstrated, with a marked increase in the number of nerve fibres and terminals with neuropeptide Y and tyrosine hydroxylase. In a few patients a hyperinnervation with VIPergic or SPergic nerves was seen. These findings indicate that hyperactive local nervous reflexes are of pathogenetic importance. To silence such activity, the diseased mucosa was treated with topically applied lidocaine. Such topical treatment with lidocaine gel in 21 consecutive patients with UP/PS for 3-8 weeks caused a rapid decrease of subjective and objective symptoms. During treatment mucosal integrity was restored, accompanied by depletion of OKT4 and OKT8 lymphocytes from the mucosa. However, the hyperinnervation pattern persisted during treatment. PMID- 2595268 TI - Gastric vascular ectasias in cirrhosis: association with hypoacidity not related to gastric atrophy. AB - To investigate whether hypergastrinemia and low serum levels of pepsinogen I are associated with gastric hypoacidity in cirrhosis with capillary ectasia of gastric mucosa and whether this alteration is secondary to the presence of atrophic gastritis, two groups of patients were studied: 1) 12 cirrhotic patients with diffuse gastric red spots at the endoscopic examination, and 2) 12 cirrhotic patients with endoscopically normal mucosa. Vascular ectasia of the gastric mucosa was histologically confirmed in all patients with gastric red spots. The study of base-line and stimulated acid gastric secretion showed that 9 of 12 (75%) cirrhotics with gastric vascular ectasia had achlorhydria and that 8 of these 9 patients had high base-line gastrin serum levels (greater than 130 pg/ml) and low base-line pepsinogen I serum levels (less than 20 ng/ml). Base-line gastrin and pepsinogen I serum levels were significantly greater and lower, respectively, in patients with gastric vascular ectasias than in cirrhotics without these lesions. None of the patients of either group had complete atrophy in the corpus of the stomach, and only 4 of the 9 cirrhotics with gastric vascular ectasia and achlorhydria had moderate atrophy. These results show that achlorhydria is frequently associated with hypergastrinemia and low pepsinogen I serum levels in patients with cirrhosis and gastric vascular ectasias and suggest that this disturbance is not secondary to a morphologic abnormality of the gastric mucosa. PMID- 2595269 TI - Serotonin--a possible transmitter for the gastric adaptive relaxation. Interaction with histamine and prostaglandin F2 alpha on pressure responses in the isolated stomach. AB - Serotonin, or 5-hydroxytryptamine (5-HT), relaxes upper guinea pig stomach, and its possible role as a transmitter in the vagally induced upper gastric adaptive relaxation has been discussed. Such a transmitter is expected to act via other mechanisms than crude muscle depression. To test whether the relaxation response to serotonin is compatible with a putative role as transmitter in gastric adaptive relaxation, we wanted to evaluate whether serotonin acts by crude muscle depression and whether it selectively inhibits histamine or prostaglandin F2 alpha (PGF2 alpha). The study shows that 5-HT, in addition to its relaxatory effect on fundic spontaneous activity, selectively inhibits histamine, whereas PGF2 alpha is not inhibited. It is then concluded that the relaxatory effect of 5 HT is provided through other mechanisms than crude muscle depression and that selective inhibition of intramural agonists, like histamine, is a possible effect mechanism. PMID- 2595270 TI - Absorption of water and solute from glucose-electrolyte solutions in the human jejunum: effect of citrate or betaine. AB - The inclusion in oral rehydration solutions of solutes that are actively co transported with sodium has been suggested as a means of increasing the effect of glucose on water absorption by the small intestine. Using a modified perfusion system we have examined water and solute absorption in the normal human intestine from two effervescent glucose-electrolyte solutions, containing either citrate or betaine hydrochloride, and compared the absorption rates with those from a commonly used bicarbonate-containing oral rehydration solution. Absorption of citrate (355 +/- 87 mumol/cm/h) and betaine (313 +/- 125 mumol/cm/h) occurred from the respective solutions. The inclusion of 46 mmol/l citrate or 36 mmol/l betaine in effervescent oral rehydration solutions had no effect on water or solute absorption. PMID- 2595271 TI - Duodenal acidification and jejunal hyperosmolality inhibit pentagastrin stimulated acid secretion in chronic gastric fistula rats. AB - In chronic gastric fistula (GF) rats, HCl and a hyperosmolal solution of polyethylene glycol (PEG) in the upper intestine inhibit pentagastrin-stimulated gastric acid secretion by different mechanisms, but their anatomic sites have not yet been established. In the present study GF rats were provided with Thiry-Vella loops of the duodenum and the bile and pancreatic ducts transplanted to the proximal jejunum, or with Thiry-Vella loops of the proximal jejunum. In the latter rats the duodenum was anastomosed as a blind loop to the jejunum to prevent any gastric juice from entering the duodenum. Duodenal loop perfusion with 0.20 M HCl inhibited the acid response to pentagastrin by 62%, but perfusion with 1200 mOsmol x kg-1 of PEG solution did not alter the response. In contrast, acidification of the proximal jejunal loop did not alter but hyperosmolality inhibited the response by 41%. The study shows that the mechanism for inhibition by intestinal acidification is confined to the duodenum and that for inhibition by hyperosmolality is located in the proximal jejunum--but whether only to the proximal part is unknown. PMID- 2595272 TI - Delayed gastric ulcer healing after extirpation of submandibular glands is sex dependent. AB - This study examines the effect of excision of the submandibular salivary glands, the main source of epidermal growth factor (EGF), and the role of gender on the healing of acetic acid-induced gastric ulcers in rats. In male rats excision of the submandibular glands delayed ulcer healing. At 15 and 25 days the unhealed ulcer areas were significantly larger in the sialoadenectomy group than in control animals, and fewer completely healed ulcers were seen in this group at 25 days. Ulcer healing in female rats was slower. At day 25 ulcers were healed in 12% of female rats with intact salivary glands, compared with 68% in males. Female rats also showed larger unhealed ulcer areas after sialoadenectomy than controls. We conclude that removal of the main source of EGF in the gastrointestinal tract is associated with a delay in healing of gastric ulcers. The significant difference in healing observed between female and male rats may be influenced by the known androgenic regulation of EGF production in the salivary glands. PMID- 2595273 TI - Gastroprotection by an aluminium- and magnesium hydroxide-containing antacid in rats. Role of endogenous prostanoids. AB - This study was designed to determine the gastroprotective actions of an antacid (Maalox 70) and its components, Al(OH)3 and Mg(OH)2, against acute gastric lesions induced by absolute ethanol, acidified aspirin (ASA), and water immersion and restraint stress in rats. Given orally, the antacid prevented dose dependently the formation of gastric lesions by all three ulcerogens, and these effects were similar to those obtained with a methylated prostaglandin E2 (PGE2) analog. Active Al(OH)3 gel was equipotent with Maalox, whereas Mg(OH)2 was significantly less effective in gastroprotection than Maalox 70. Chemically inactive Al(OH)3 wet gel showed only small and insignificant protective properties. Since the gastroprotective activities of Maalox 70 against ethanol lesions cannot be reversed by pretreatment with indomethacin, and since neither Maalox 70 nor its active components affected the mucosal generation of PGE2 and leukotriene C4, we postulate that mucosal prostanoids are not the primary mediators in the mechanism of their protective action on the gastric mucosa. PMID- 2595275 TI - Lower esophageal sphincter pressure, esophageal body motor functioning, and esophageal acid sensitivity. AB - Esophageal acid sensitivity is believed to develop as a result of esophageal acid exposure, contributing factors being gastroesophageal reflux and delayed esophageal acid clearance. The relationship among lower esophageal sphincter pressure, motor functioning of the body of the esophagus, and esophageal acid sensitivity was examined by comparing the results from 912 patients and normal subjects studied with both esophageal manometric and Bernstein acid infusion tests. Positive acid infusions were statistically more closely associated with hypotensive lower esophageal sphincter pressures than with any motor abnormality in the body of the esophagus. Of the several esophageal body motor abnormalities considered, only feeble peristalsis had significantly more positive Bernstein tests than did normal esophageal body motor functioning. The findings from this study demonstrate that hypotensive lower esophageal sphincter pressure is more closely associated with an acid-sensitive esophagus than is impaired esophageal body motor functioning. PMID- 2595274 TI - 99mTc-sucralfate scintigraphy in inflammatory bowel disease. AB - Technetium-99m-labeled albumin-sucralfate was orally administered to 11 patients (Crohn's disease, 8; ulcerative colitis, 3) and 3 healthy volunteers. Serial scintigraphy was performed, and scintigraphic interpretations were compared with radiographic and endoscopic findings in an open study. We were not able in any patient to relate the scintigraphic findings to the localizations of inflammatory bowel disease, nor could we distinguish the scans in the patients from the scans of the healthy volunteers. We conclude that 99mTc-albumin-sucralfate scintigraphy is of no value in the detection of inflammatory bowel disease. PMID- 2595276 TI - Culture of normal and inflamed rabbit colonic explants. Medium-term prostaglandin profile. AB - Rabbit colonic biopsy specimens cultured under well-standardized conditions showed a linear uptake of leucine, thymidine and arachidonic acid (AA) for at least 48 h. Prostaglandin E2 (PGE2) production displayed a time-dependent profile. Initial high and fluctuating levels were seen as a result of the preparation trauma. Within 5-7 h a semi-steady state was reached. Addition of the Ca++ ionophore A23187 significantly increased PGE2 production throughout the 48-h time course, but stimulation was optimal (fivefold) around 6 h, as compared with two- to three-fold at 24 and 48 h. Phorbol 12-myristate 13-acetate stimulation of biopsy specimens labelled for 24 h with 14C-AA showed significantly higher proportional release of 14C-PGE2 than after A23187 or a combination of both, indicating stimulus utilization of different AA pools, with variable turnover. Mucosa from rabbits with acetic acid-induced colitis demonstrated a significantly increased leucine incorporation during the first 24-h period and normal incorporation during the second period. PGE2 production reached a high A23187 insensitive maximum at 24 h. This study shows the importance of sample timing, the existence of different AA pools, and the feasibility of studying inflamed mucosa in medium-term tissue culture. PMID- 2595277 TI - Efficacy and safety of long-term maintenance therapy of duodenal ulcers. AB - The efficacy and safety of continuous (maintenance) treatment with ranitidine has been studied retrospectively in 388 patients with duodenal ulcer. The cumulative rate of symptomatic relapse was 16% after 5 years. Very few of the patients developed ulcer complications during maintenance treatment, with a cumulative risk of haemorrhage of 1.8% during 5 years. The patients developed no drug related disease. We conclude that long-term, continuous treatment with ranitidine is effective in maintaining remission of duodenal ulcers, protects the patients against the risk of complications, and is safe. PMID- 2595278 TI - Peptic ulcer research in Japan. Proceedings of the 16th annual meeting of the Experimental Ulcer Association of Japan. Kyoto, Japan, 2 December 1988. PMID- 2595279 TI - Alteration of gastroduodenal acetylcholine metabolism induced by 2-deoxy-D glucose in rats. AB - The effect of 2-Deoxy-D-glucose (2-DG) on acetylcholine (ACh) metabolism in the stomach and duodenum of rats was studied. 2-DG significantly increased [3H] choline uptake, [3H] ACh synthesis, and choline acetyltransferase and acetylcholinesterase activities in parallel with an increase in gastric acid secretion. The conversion rate of uptaken [3H] choline to [3H] ACh, the turnover rate of ACh, and the contents of ACh and choline were negligibly influenced by 2 DG. 2-Buten-4-olide, which inhibits vagus nerve activity via the central nervous system, prevented the 2-DG increased [3H] choline uptake and subsequent [3H] ACh synthesis as well as the increase in gastric acid secretion. These results suggest that neuronal activity of the vagus nerve is coupled with [3H] choline uptake and subsequent [3H] ACh synthesis, and that cholinergic neuronal activity depends on quantitative changes in ACh metabolism in the gastroduodenum. PMID- 2595280 TI - Effects of the duodenal ulcerogens, mepirizole and cysteamine, on gastric motility and emptying in rats. AB - Mepirizole (60 and 200 mg/kg, s. c.) and cysteamine (100 and 300 mg/kg, s. c.) markedly inhibited gastric motility in fasted rats. The inhibition caused with the low dose (non-ulcerogenic) of each agent reverted to control levels within 6 h. With high doses (ulcerogenic), however, the inhibition persisted for more than 9 h, and returned to control levels 12 h later. Gastric emptying of liquids was significantly delayed with ulcerogenic and non-ulcerogenic doses of the agents. Delayed emptying (gastric contents) persisted for 12 h with ulcerogenic doses, The pathogenetic relevance of this prolonged inhibition of gastric motility and emptying to ulcerogenecity was considered. PMID- 2595281 TI - Roles of gastric acid secretion and motility in gastric mucosal lesion formation induced by water-immersion stress in rats. AB - The roles of gastric acid and motility in gastric mucosal lesion formation induced by water-immersion stress were studied pharmacologically in rats. Gastric acid secretion and motility increased markedly during water-immersion, and mucosal lesions were formed. Cimetidine inhibited the increase in gastric acid secretion, but papaverine inhibited the increases in both acid secretion and motility. Both agents prevented the formation of mucosal lesions. In acid perfused rats, the increase in motility and lesion formation induced by water immersion stress were prevented by papaverine, but not by cimetidine. These results suggest that the increases in both acid secretion and motility play important roles in the formation of mucosal lesions induced by water-immersion stress in rats. PMID- 2595282 TI - Changes in levels of mucosal glycoprotein on cysteamine-induced duodenal ulcers in rats. AB - Duodenal ulcers were induced in rats by cysteamine administration. Time-course changes in duodenal hexosamine, blood flow and intragastric pH were measured, as well as changes in the susceptibility of Brunner's glands to concanavalin A (Con A) staining. Hexosamine contents in the duodenum decreased significantly at 5 and 24 h. In the control group, Brunner's glands were stained brown using Con A staining. One day after cysteamine administration, the extent of Con A staining markedly decreased. At 3 and 7 days, gland susceptibility to staining was essentially the same as that of the control group. PMID- 2595283 TI - Pathogenesis of water-immersion stress-induced gastric ulcers in rats with renal failure. AB - Rats with or without renal failure, produced by uranyl acetate, were subjected to water-immersion stress for 6 h. The severity of stress-induced gastric ulcers in the renal failure group was significantly higher than that in the control group. The intragastric pH did not significantly differ between the two groups. Transmucosal electrical potential difference, gastric mucosal blood flow, and gastric mucosal hexosamine content in the renal failure group were significantly lower than in the control group. These results suggest that decreases in defensive factors, rather than an increase in an aggressive factor, may be more closely involved in the development of acute gastric ulcers in rats with renal failure. PMID- 2595284 TI - Gastric mucosal protective action of endothelium-derived relaxing factor. AB - The change in the endothelial function by the application of 0.6 N HCl and the effects of endothelium-derived relaxing factor (EDRF) inhibitors and nitrites on HCl-induced lesions were studied to clarify the effect of EDRF on gastric lesions in rats. The EDRF-induced increase in the gastric mucosal hemodynamics induced by vagal stimulation or intra-arterial administration of acetylcholine was inhibited by the EDRF inhibitors or removal of endothelial cells. Topical application of 0.6 N HCl on the exposed gastric mucosa abolished the response of the mucosal hemodynamics to acetylcholine or vagal stimulation. Gastric lesions induced by 0.45 N HCl were enhanced by EDRF inhibitors or removal of endothelial cells from gastric submucosal arterioles. PMID- 2595285 TI - Inhibitory effect of peptide YY on gastric acid output in rats. AB - The administration of peptide YY (PYY: 0.8, 1.6 and 3.2 nmol/kg/h, i.v.) to fasting rats inhibited not only baclofen (2 mg/kg, s.c.)-stimulated gastric acid output and gastric mucosal blood flow, but also pentagastrin (8 micrograms/kg/h, i.v.)-stimulated gastric acid output. PYY (3.2 nmol/kg/h) reduced baclofen induced acid output more than pentagastrin-induced acid output, i.e., by 61.8 +/- 11.5% compared to 35.3 +/- 8.2%. PYY inhibited acetylcholine (ACh) release from cholinergic nerve endings of gastric body evoked by electrical transmural stimulation (ETS: 1 msec, 10 V, 3 Hz, 30 sec) by 47.2 +/- 3.5%. The mechanism of the inhibitory effect of PYY on gastric acid output seems to involve decreased gastric mucosal blood flow and reduced ACh release from cholinergic nerves. PMID- 2595286 TI - Characterization of metalloproteinases in rat gastric tissues with acetic acid induced ulcers. AB - To clarify the destruction of connective tissue in ulcerated regions, collagenase and gelatinolytic activities in homogenates of rat acetic acid-induced ulcers were examined. Gelatinolytic activity in the ulcerated regions was significantly higher than that in normal tissues. Collagenase, however, was not detectable. Gelatin-gel-electrophoresis showed that the gelatinolytic activity was due to several species, some of which crossreacted with a sheep anti-(rabbit prostromelysin) antibody. The H2-blocker, famotidine, significantly depressed the gelatinolytic activity in the ulcerated regions. Thus, both stromelysin and gelatinolytic enzymes may play important roles in the degradation of the basement membrane, especially type IV collagen. PMID- 2595287 TI - Influence of food-intake during a fixed period on hydrocortisone-induced relapse of acetic acid ulcers in rats. AB - We studied the influence of food-intake during a fixed period on hydrocortisone induced relapse of acetic acid ulcers in rats. The ulcer index, the defective area of the ulcerated region and the exposure index for the ulcer floor in the food-intake-time limited group markedly increased as compared to those in the control group. The index for the regenerated mucosa decreased in the food-intake time limited group. Thus, hydrocortisone-induced relapsed ulcers were markedly increased by limiting the food-intake-time. PMID- 2595288 TI - Role of the mucus gel layer in the healing of acetic acid-induced gastric ulcers in rats. AB - Changes in the pH gradient and thickness of the mucus gel layer in the healing of acetic acid-induced gastric ulcers in rats were investigated. The maximum of the pH gradient and the thickness of mucus gel layer at the edge of ulcers and in the regenerated mucosa were higher, decreased gradually with the healing of the ulcers and finally reached normal values. This indicates that mucus and bicarbonate are secreted actively from the mucosa surrounding an ulcer and that they play an important role in protection of the base of ulcers and in acceleration of the healing of the ulcers. PMID- 2595289 TI - Effects of human epidermal growth factor on natural and delayed healing of acetic acid-induced gastric ulcers in rats. AB - We examined the effect of human epidermal growth factor (hEGF) on the healing rate of gastric ulcers induced in rats. These ulcers were produced by a submucosal injection of 0.03 ml of 20% acetic acid into the stomach. Healing of the ulcers was delayed when a daily s.c. injection of indomethacin (1 mg/kg) was given for 4 wks. hEGF (100 and 300 micrograms/kg), given s.c. for 2 and 4 wks, significantly accelerated both natural and delayed healing of the ulcers. hEGF significantly inhibited both basal (pylorus ligation) and histamine-stimulated acid secretion (acute fistula). Thus, hEGF accelerates the healing of acetic acid induced gastric ulcers, presumably because of its potent antisecretory activity. PMID- 2595290 TI - Quantitative assessment of mild stages of experimental gastritis in the rat and the effects of several types of antiulcer drugs. AB - A novel method was developed to evaluate acute gastric mucosal lesions (AGML) quantitatively in conscious rats. The gastric lumen was continuously irrigated with saline and the number of red blood cells that leaked into the perfusate was determined. Restraint stress caused a slight increase in gastric bleeding. Indomethacin and aspirin, produced significant bleeding from the gastric mucosa. The gastric hemorrhage in response to indomethacin was suppressed by atropine, cimetidine, and dmPGE2, but worsened by mepyramine. New types of antiulcer drugs, cetraxate and sofalcone were also effective in inhibiting the gastric hemorrhagic amount. It is concluded that this model is useful for studying the pathogenesis of AGML, the effectiveness of drugs on AGML, and the adverse effects of new drugs on the digestive tract. PMID- 2595291 TI - Augmentation of the gastric mucosal defense mechanism induced by KW-5805, a novel antiulcer agent. AB - KW-5805 (a new antiulcer agent), given p. o. at 30 mg/kg to rats, significantly increased the amount of gastric adherent mucus and mucosal glycoproteins. Gastric mucosal glucosamine synthetase activity was significantly enhanced by KW-5805 (30 mg/kg, p. o.). KW-5805 (10, 30 mg/kg, p. o.) significantly suppressed the decrease of gastric mucosal blood volume and oxygen sufficiency induced by hemorrhagic shock. The agent also significantly inhibited the extravasation of Evans blue into the gastric mucosa after ischemia-reinfusion. In conclusion, KW 5805 increased biosynthesis, storage and secretion of gastric mucus and improved the gastric mucosal hemodynamics. PMID- 2595292 TI - Mechanism of anti-ulcer effect of calf blood extract. AB - The mechanism of anti-ulcer effect of Solcoseryl, an extract from calf blood, was studied. Solcoseryl (10 ml/kg, i. v.) increased basal and chemically reduced potential difference of the gastric mucosa in rats. Solcoseryl (1-10 ml/kg, i.v.) also increased gastric mucosal blood flow and gastroduodenal HCO3- secretion. These results indicate that Solcoseryl has a mucosal protective effect which may contribute to the mechanism of its anti-ulcer effect. PMID- 2595293 TI - Effects of ALE-36 on gastric secretion, and gastric and duodenal ulcers induced in rats. AB - We examined the antisecretory and anti-ulcer effects of ALE-36 in rats. ALE-36 (3 30 mg/kg) dose-dependently inhibited gastric acid secretion in pylorus-ligated rats. However, the agent apparently increased the volume of gastric juice, and the Na+ and Cl- ion outputs. These changes were almost completely prevented by pretreatment with indomethacin, suggesting that endogenous prostaglandins in the gastric mucosa mediated the changes. Pretreatment with ALE-36 (3-30 mg/kg) inhibited the development of stress-, aspirin-, and indomethacin-induced gastric lesions, and mepirizole-induced duodenal ulcers. Repeated administration of ALE 36 significantly accelerated the healing of gastric ulcers induced by thermocautery. PMID- 2595294 TI - Influence of water-immersion stress on synthesis of mucus glycoprotein in the rat gastric mucosa. AB - Gastric mucous cells of rats subjected to water-immersion stress were incubated with [3H]-palmitic acid and [14C]-N-acetylgalactosamine. The peptidyl-tRNA released by gastric polysomes was precipitated with cold ethanol and then the content was determined. A 70% reduction in the peptidyl-tRNA isolated was observed in the stressed rats, as compared with in control rats. The peptide recovered from the peptidyl-tRNA showed 30-50% less [3H]-palmitic acid and [14C] N-acetylgalactosamine incorporation in the stressed rats than in normal controls. It was thus suggested that translation, acylation and glycosylation of the peptides in the ribosomes of the gastric mucosa were remarkably affected by the stress. PMID- 2595295 TI - The effect of DQ-2511, a newly synthesized anti-ulcer drug, on the gastric mucosal hemodynamics and ulceration in rats. AB - DQ-2511, which is a dopamine derivative, is a newly synthesized anti-ulcer drug. Pretreatment with DW-2511 in the hemorrhagic shock-reperfusion model in rats significantly prevented the decreases of gastric mucosal blood volume, mucosal blood oxygenation index and the ulcer formation. The decrease in gastric mucosal blood oxygenation index in hemorrhagic shock state has a linear correlation with the size of the mucosal ulcers both in DQ-2511 and control groups. The results suggested that DQ-2511 exerts its anti-ulcer activity by improving mucosal hemodynamics in hemorrhagic shock-reperfusion rat model. PMID- 2595297 TI - Effects of hEGF (MG111) on gastric mucosal potential difference in rats. AB - hEGF (GMG111) given i. v. significantly and dose-dependently suppressed the reduction in gastric mucosal potential-difference (PD) induced by 30% ethanol in rats. Pretreatment with indomethacin did not affect its effect, thereby suggesting that endogenous prostaglandins will not be involved in the mechanism of action of MG111. These results indicate that MG111 protects the weakening of "gastric mucosal barrier". The PD was significantly reduced when MG111 was given i. v. at 20 micrograms/kg. This reduction caused by MG111 was not affected by pretreatment with atropine, hexamethonium, propranolol, and phentolamine. PMID- 2595296 TI - Thromboxane A2 antagonistic action of a new anti-ulcer agent, azuletil sodium (KT1-32). AB - The TXA2/PGH2 receptor antagonistic activity of azuletil sodium (KT1-32), a new anti-ulcer agent, was examined. KT1-32 competitively antagonized the contraction of canine gastric arteries induced by U-46619, PGF2 alpha, and PGE2, whereas it had no effect on the PGF2 alpha-, PGE2- and LTD4-induced contraction of guinea pig ileum, which was not affected by U-46619. In anesthetized dogs, KT1-32 significantly reduced the U-46619-induced decrease in gastric arterial blood flow. Gastric contraction induced by U-46619 in anesthetized rats was markedly inhibited by KT1-32. KT1-32 showed no influence on TXA2 synthetase and cyclooxygenase activities. These results indicate that KT1-32 is a competitive TXA2/PGH2 receptor antagonist, which may be important as to the effectiveness of KT1-32 against gastric ulcer. PMID- 2595298 TI - The role of the sympathetic nervous system in cysteamine-induced gastric lesions in rats. AB - Cysteamine.HCl, when administered subcutaneously at 350 mg/kg, consistently induced severe gastric lesions in Wistar Kyoto rats (WKY), but not in spontaneously hypertensive rats (SHR). In both WKY and SHR, visible ulcers could not be induced in the duodenum in response to cysteamine. It appears that the stomach and duodenum of SHR are resistant to cysteamine due to hyperfunctioning of the sympathetic nervous system. PMID- 2595300 TI - Role of eicosanoids and related mediators in gastric mucosal ulceration. PMID- 2595299 TI - Epidermal growth factor inhibits cysteamine-induced duodenal ulcers in rats. AB - We examined the pathogenesis of cysteamine-induced duodenal ulcers in rats, especially with reference to epidermal growth factor (EGF). Control, cysteamine (400 mg/kg, s.c.), cysteamine + EGF (20 micrograms/kg/day, i.p.) submandibular resection (SMR), SMR + cysteamine, and SMR + cysteamine + EGF groups were examined for duodenal ulceration. With submandibular resectioning, endogenous EGF decreased, and with the administration of EGF (i.p.), endogenous EGF increased. In the SMR + cysteamine group, serum gastrin increased and the intragastric pH decreased remarkably compared to in the normal control group. The administration of exogenous EGF suppressed this change. Mucosal blood flow, the potential difference and hexosamine, as defensive factors, decreased markedly in the SMR + cysteamine group, but the administration of exogenous EGF reversed these changes. These results suggested that a decrease in EGF is involved in the pathogenesis of cysteamine-induced duodenal ulcers in rats. PMID- 2595301 TI - Biological significance of phospholipids in the rat stomach--from the viewpoint of electron microscopy. AB - The structures of gastric phospholipids (PLs) were further confirmed by employing an improved fixative and fixation method. PLs were detected on the free surface of superficial mucous epithelial cells and epithelial cells of the foveolar crypts. PLs were also detected inside superficial mucous cells and epithelial cells of the foveolar crypts. The gastric PLs were secreted through a merocrine like mechanism. Apocrine-like secretion of PLs was also observed in some electron microscopic images. PLs were observed in the intercellular and intracellular secretory canaliculi of parietal cells and also in the rest of the parietal cytoplasm. The above findings indicated the localization of PLs on the surface of the gastric lumen and in the gastric mucosa, and suggested that, similar to gastric glycoproteins, gastric PLs play an important role in the gastric mucous barrier and mucosal barrier. PMID- 2595302 TI - Fluctuation of the mucosal hydroxyproline content in compound 48/80-induced gastric lesions in rats. AB - Extensive gastric mucosal lesions were observed after i.p. administration of compound 48/80 (0.75 mg/kg) for 3 days to rats. The mucosal hydroxyproline content was significantly increased at 4 h after the last injection of compound 48/80 and subsequently decreased as the lesions were healed. Treatment with cimetidine (50 mg/kg, i.p.) did not prevent compound 48/80-induced gastric lesions. The increase in the mucosal hydroxyproline content was significantly reduced by treatment with cimetidine. This fact suggested that cimetidine might have an inhibitory effect on the regeneration of connective tissue. PMID- 2595303 TI - In vitro measurement of the pH gradient and thickness of the duodenal mucus gel layer in rats. AB - The mucus bicarbonate barrier of the duodenum has lately been reported to be one of the most important defensive factors for the duodenal mucosa. We established an in vitro system for evaluating the mucus bicarbonate barrier in the rat duodenum. Our method allows direct measurement of the pH gradient as well as the thickness of the mucus gel layer of the rat duodenum in vitro. The obtained results suggest that alkali secretion in response to acid-loading as well as the thickness of the duodenal mucus gel layer are greater than those in the stomach. PMID- 2595304 TI - Effect of the luminal hydrogen ion on alkali and mucus secretion in the rat stomach. AB - This study was designed to investigate the effect of luminal H+ on alkali and mucus secretion in the isolated rat stomach. At various luminal pHs, the thickness and the pH gradient of the mucus gel layer were measured. The maximum pH and calculated alkali secretion showed that the latter was stimulated in parallel with an increase in luminal H+ concentration, especially when the luminal pH became less than 3.5. Mucus secretion, however, was not significantly affected by the luminal H+ concentration. These results suggest that alkali and mucus secretion in the stomach are not regulated by the same mechanism, but different ones. PMID- 2595305 TI - Changes in the intracellular calcium ion concentration in the gastric mucosa in a rat ischemia-reperfusion model. AB - To investigate the role of the intracellular calcium ion in the development of acute gastric mucosal lesions, phosphorylase a activity was measured as an index of the intracellular calcium ion concentration ([Ca2+]i), using Lowry's method, in the rat ischemia-reperfusion model. [Ca2+]i increased significantly at the end of the ischemic state without acute mucosal lesions (AGML). After reinfusion, [Ca2+]i showed a slight increase and AGML developed. Continual intravenous infusion of the calcium channel blocker, diltiazem (1 mg/kg/hr), inhibited the increase in [Ca2+]i in the ischemic state and reduced the development of AGML after reinfusion. These results suggest that the increase in [Ca2+]i in the ischemic state plays an important role in the development of AGML. PMID- 2595306 TI - The role of oxygen radicals in the pathogenesis of gastric mucosal lesions induced in mice by feeding-restriction stress. AB - To investigate the role of oxygen radicals in the pathogenesis of gastric mucosal lesions induced by psychological stress, we exposed 3-mo-old C3H mice to feeding restriction stress for 1 to 5 days. Serial changes in the activities of antioxidant enzymes in the gastric mucosa, together with O2- production by macrophages, were measured. The stress increased the plasma cortisol level and started to produce acute gastric lesions (AGL) on the 2nd day. Before the development of AGL, the activity of superoxide dismutase in the gastric mucosa had already decreased and the ability of O2- production by macrophages was enhanced from the 1st day. This suggests that oxygen radicals play some role in the development of AGL induced by the stress. PMID- 2595308 TI - Serum platelet-activating factor acetylhydrolase activity in rats with gastric ulcers induced by water-immersion stress. AB - Platelet-activating factor (PAF) acetylhydrolase is an enzyme which hydrolyzes PAF to yield inactive lysoPAF. This study focused on the influence of water immersion stress on serum PAF acetylhydrolase activity. The enzyme activity was determined by measurement of [3H]acetate produced from 1-O-alkyl-2-[3H]acetyl-sn glycero-3-phosphocholine upon precipitation of the complex of the radioactive substrate and albumin with trichloroacetic acid. The onset of water-immersion stress caused the development of gastric lesions associated with a significant increase in serum PAF acetylhydrolase activity. Serum PAF acetylhydrolase may leak into the blood from some tissues in rats with gastric injury induced by water-immersion stress and might control the action of PAF. PMID- 2595307 TI - Role of free radicals and lipid peroxidation in gastric mucosal injury induced by ischemia-reperfusion in rats. AB - Ischemia and reperfusion are of the greatest importance in the pathology of many diseases. We investigated the roles of oxygen-derived free radicals and lipid peroxidation in gastric mucosal injury, such as spotty and linear hemorrhagic erosions, induced in rats by ischemia-reperfusion. The gastric mucosal injury and the increase in thiobarbituric acid (TBA) reactants in the gastric mucosa induced by ischemia-reperfusion were significantly inhibited by treatment with SOD and catalase. These results suggest that oxygen-derived free radicals and lipid peroxidation play important roles in the pathogenesis of acute gastric mucosal lesions induced by ischemia-reperfusion. PMID- 2595309 TI - Healing process of experimental esophageal ulcers induced by acetic acid in rats. AB - We studied the healing of acetic acid-induced esophageal ulcers in rats with respect to the cellular kinetics. Esophageal ulcers were induced by topical application of acetic acid to the serosal surface. Well-demarcated circular or elliptical ulcers had developed by day 3 after the acid treatment. These ulcers began to decrease in size from day 7 and had healed by day 14. Histological and cellular kinetic findings, with bromodeoxyuridine (BrdU), were degeneration of the esophageal mucosa on day 1 and ulcer formation on day 3, with an increase in the number of BrdU-labeled cells in the esophageal mucosa around the ulcer. On day 7, regenerated epithelium was found to extend towards the ulcer base and the regenerated epithelium had become thicker, with papilla formation, by day 10. On day 14, the ulcer base was covered with thickened regenerated mucosa, with a decrease in the number of BrdU-labeled cells. Marked proliferative activity of the regenerated mucosa and thickening of the esophageal mucosa, with papilla formation, were observed during the healing process. PMID- 2595310 TI - Role of PAF in ischemia-reperfusion injury in the rat stomach. AB - Ischemia-reperfusion induced extensive gastric mucosal injury and an increase in chemiluminescence activity of neutrophils obtained from the portal vein in hemorrhagic shock rats. CV-3988, a selective antagonist of platelet activating factor (PAF), significantly reduced the gross and histologic gastric damage, and the increase in chemiluminescence activity of neutrophils. These results suggest that PAF generated on hypoxia might stimulate oxygen radical production by neutrophils, resulting in the occurrence of gastric injury in hemorrhagic shock rats. PMID- 2595311 TI - Gastric mucosal damage induced in rats by intravenous administration of platelet activating factor. AB - We examined the time courses for gastric mucosal hemodynamics and lipid peroxides after intravenous infusion of PAF (platelet-activating factor). The gastric mucosal hemodynamics were continuously monitored by laser-Doppler flowmetry and reflectance spectrophotometry during 20 min infusion of PAF and the subsequent 60 min. Gastric mucosal damage was assessed by microscopical scoring and measurement of thiobarbituric acid (TBA) reactants. Intravenous infusion of PAF caused macroscopical gastric mucosal damage, hemodynamic disturbance, a reduction in blood pressure and elevation of TBA reactants. These changes did not recover to control levels, even at 60 min after PAF infusion. The mucosal injury caused by the hemodynamic disturbance (congestion) was related to the elevation of TBA reactants, that reflect lipid peroxidation and oxygen-derived free radicals. PMID- 2595312 TI - Platelet activating factor induced gastric damage in rats: participation of increased gastric vascular permeability. AB - Pharmacological factors involved in the injurious effect of platelet activating factor (PAF) on the gastric mucosa were studied in the acid (0.15 N HCI)-perfused stomachs of anesthetized rats. PAF infusion (100 ng/kg/min for 20 min, i.v.) induced distinct bleeding in the acid perfusate in proportion to mucosal lesions. Preceding the bleeding, a remarkable increase in mucosal vascular permeability was observed on dye-leakage assessment. Inhibition of the gastric bleeding and the dye leakage was achieved by pretreatment of the animals with CV-3988, a PAF antagonist, and hydrocortisone acetate, in contrast to the aggravation by caffeic acid. These results suggested the importance of mucosal vascular permeability in PAF-induced gastric mucosal lesions. PMID- 2595313 TI - A study on gastric ulcers induced by long-term fasting in rats. AB - The present study was performed to investigate the roles of intragastric pH and PAS positive mucus as to the incidence of gastric ulcers after long-term fasting in rats. Gastric ulcers in the forestomach and corpus were found at 4 and 6 days after fasting, respectively. The intragastric pH was significantly reduced at 1, 2, 3, 4, 6 and 7 days after fasting, but tended to have returned to control levels at 8 days. PAS positive mucus was significantly increased at 2 to 7 days, but there was no significant change at 8 days. From these results, it seems that the aggressive factor is not involved, but attenuation of the defensive factor is important as to the incidence of this type of ulcer. As one of the causes of this attenuation, a decrease in the gastric mucus volume was suggested. PMID- 2595314 TI - The relationship between adaptive cytoprotection and prostaglandin contents in the rat stomachs after oral administration of 0.35 N HCl. AB - Oral administration of a mild irritant, 0.35 N HCl, protected the gastric mucosa of rats against 0.6 N HCl-induced gastric lesions for 2 h. With prior administration of 0.35 N HCl, the PGE2 and PGF2 alpha contents in the fundic mucosa, as measured with a capillary gas chromatograph and a mass spectrometer, significantly increased until 1 h, but the PGD2, 6-keto-PGF1 alpha and TXB2 contents did not increase. These results suggest that the increases in gastric mucosal PG contents caused by the mild irritant protect the gastric mucosa against the strong irritant indirectly. PMID- 2595316 TI - Effects of carbenoxolone and prostaglandin E2 on transmucosal potential difference in the rat stomach. AB - The effects of prostaglandins (PGs), carbenoxolone and some pharmacological agents on the gastric transmucosal potential difference (PD) were examined under ethanol challenge in anesthetized rats. The PD reduction induced by indomethacin + ethanol (20%) was clearly prevented by PGE2 or carbenoxolone, as well as by isoproterenol or i.v. NaHCO3 infusion. The degree of the protection and recovery of the PD change with carbenoxolone (3 mg/kg, i.g.) were found to be much greater than in the case of PGE2 (100 micrograms/kg, i.g.). The importance of gastric mucus was suggested in comparison with bicarbonate secretion and mucosal blood flow. PMID- 2595315 TI - Taurocholate-induced gastric damage in rats with obstructive jaundice. AB - We examined the severity of taurocholate-induced gastric mucosal damage in rats with obstructive jaundice. Oral administration of 100 mM taurocholate induced severer gastric mucosal damage in rats with jaundice than in intact rats. Pretreatment with 5 mM taurocholate significantly protected the gastric mucosa against 100 mM taurocholate-induced damage, suggesting adaptive cytoprotection in rats with jaundice. The reductions in the gastric mucosal potential difference and hexosamine contents in the gastric mucosa in response to 100 mM taurocholate were significantly attenuated by prior administration of 5 mM taurocholate in both intact rats and rats with jaundice. PMID- 2595317 TI - The role of prostaglandin D2 in the genesis of indomethacin-induced gastric lesions in rats. AB - Four kinds of prostaglandins (PGs), 6-keto-PGF1 alpha, PGF2 alpha, PGE2 and PGD2, in rat gastric mucosa were decreased at 1 or 6 h after oral administration of indomethacin (2 or 12 mg/kg). With 2 mg/kg of indomethacin, the PG levels had slightly recovered 6 h later. Gastric lesions were observed 6 h after administration of indomethacin (12 mg/kg), but not with 2 mg/kg. Omeprazole (20 mg/kg, i.p.) prevented ulcer formation caused by indomethacin, without improvement of the reduced gastric mucosal PG levels. PGD2 (0.5 mg/kg, p.o.) reduced indomethacin-induced gastric lesions and considerable amounts of PGD2 existed in the gastric mucosa. We conclude that H+ is a determining factor in the genesis of indomethacin-induced gastric lesions and persistent decreases in tissue PG levels also participate in ulcer formation. PMID- 2595318 TI - Influence of aging on stress ulcer formation in rats. AB - The effects of aging on stress ulcer formation were examined in male Fischer 344 rats at 2, 8-9, 11-12, 17-18 and 21-24 months old. The animals were restrained and immersed in a water bath (22 degrees C) for 1, 2, 4 and 8 h. The incidence and severity of gastric corpus ulceration increased linearly with age. Basal acid secretion, determined 4 h after pylorus ligation, decreased with age, but there were no age-related differences in the effect on acid secretion of histamine and vagal nerve stimulation in the lumen-perfused stomachs of anesthetized rats. On morphological examination, surface epithelial cells in aged rats (21-24 months) were found to be intact, but the gastric foveolae were shallow and the chief cell layer was thick in aged rats. Deficiencies of vascular networks were observed in aged rat stomachs. These results indicate that an insufficiency of gastric mucosal microvascular networks and the preserved gastric acid response in the vulnerable mucosa may be involved in the mechanisms underlying aggravation of stress ulcer formation in aged rats. PMID- 2595319 TI - Tamoxifen treatment of idiopathic oligozoospermia: effect on hCG-induced testicular steroidogenesis and semen variables. AB - The mechanisms behind the effects of antioestrogens on semen variables and steroidogenesis in patients with oligozoospermia are unknown. In order to further elucidate this, the steroidogenic response to acute hCG-stimulation was studied in patients with idiopathic oligozoospermia before and during treatment with the antioestrogen Tamoxifen. Also an evaluation of semen variables in these patients was performed. During Tamoxifen treatment serum concentrations of LH, FSH, progesterone, 17 alpha-progesterone, testosterone and oestradiol-17 beta increased whereas no effect was observed on prolactin and SHBG concentrations. A similar pattern in steroidogenic response to hCG-stimulation was observed before and during Tamoxifen treatment. Sperm density, motility and morphology all improved after Tamoxifen treatment. The present results are discussed in relation to the possible mechanism of action of antioestrogens in patients with oligozoospermia. PMID- 2595320 TI - The influence of a urethral catheter and age on recorded urinary flow rates in healthy women. AB - Introducing a 7 F catheter into the urethra reduced the maximum and average flow rate and increased the micturition time significantly in healthy fertile and postmenopausal women. The menstrual cycle had no influence on the parameters. Urinary flow data were highly reproducible in both the fertile and the postmenopausal women. The flow rate-volume relation can be mathematically expressed, allowing for corrections when small voided volumes or small flow rates are obtained. Furthermore, this relation showed an increased flow time and a decreased flow rate in the postmenopausal women. This might indicate that the postmenopausal women had a reduced bladder contractility or a less compliant urethra. PMID- 2595321 TI - A neurophysiological study of patients undergoing radical prostatectomy. AB - 24 men suffering from localized prostatic cancer undergoing radical retropubic nerve-sparing prostatectomy were investigated by the following electrophysiological methods: Bulbocavernosus reflexes elicited from the penile skin or the posterior urethra, sensory thresholds in the posterior urethra, cerebral evoked potentials after stimulation of the pudendal nerve or the posterior urethra. 15 men were examined 4-33 months postoperatively only, 5 men were examined only preoperatively and 4 men were examined both pre- and postoperatively. 10 men suffering from minor problems due to benign prostatic hyperplasia served as controls. In patients with localized cancer of the prostate, the findings did not differ from those in the control group. In the operated group the findings were pathological in a large proportion of the patients, indicating injuries both to nervous pathways running through the pelvic nerve plexus and in the pudendal nerve. The conclusions were: Localized cancer of the prostate has minimal or no risk at all of impaired functioning in the pelvic nervous pathways. Radical retropubic prostatectomy may in some cases be undertaken without any objective evidence of injury to these nervous pathways, but is often followed by findings indicating such injury. The dorsal nerve of the penis may be affected by the operation. Transcranial stimulation of the motor cortex is a useful method in the evaluation of prolonged or absent bulbocavernosus reflexes. PMID- 2595322 TI - Evaluation of upper and lower urinary tracts after Camey operation. AB - Ten male patients with bladder carcinoma underwent radical cystoprostatectomy and Camey bladder substitution. Six months after surgery 3 of 19 ureters were refluxing in cystography. IVP demonstrated slight dilatation of two and moderate dilatation of one renal unit. The median maximum capacity of the bladder substitutes was 400 ml and the median residual volume was 40 ml. In 7 cases high pressure waves were demonstrated in cystometry. Nine patients had normal continence during day but only three patients during night. In addition three patients were dry during night if they voided frequently but four had varying degrees of enuresis. The results are otherwise satisfactory but the night-time incontinence may be troublesome. PMID- 2595323 TI - Relationship between blood groups and bladder tumors. AB - Among 89 patients with histologically verified tumor of the urinary bladder, the incidence of tumor invasion was less in the patients with blood group A than in those with blood group O. PMID- 2595324 TI - Intestinal absorption of oxalate and calcium in patients with jejunoileal bypass. AB - Jejunoileal bypass (JIB) has been widely performed for treatment of excessive obesity. Formation of calcium oxalate stones is a common side effect. Since, under physiological conditions, the intestinal absorption of calcium and that of oxalate are interrelated, intestinal oxalate and calcium absorption were measured in the present study by isotope techniques in 19 JIB patients and 20 healthy controls. The JIB patients showed pronounced hyperoxaluria and markedly increased absorption of oxalate, with a urinary excretion of 14C-oxalate of 29 +/- 19% (controls 6.2 +/- 3.7%; p less than 0.001). There was a strong correlation between the intestinal absorption and urinary excretion of oxalate in the JIB patients (r = 0.72; p less than 0.001). Furthermore, their oxalate kinetics was altered, with continued urinary excretion of 14C-oxalate for up to 48 hours. The JIB patients also had reduced calcium absorption (36 +/- 9.1% vs. 47 +/- 9.0%; p less than 0.001) and patients with malabsorption of calcium and low urinary calcium had the highest intestinal absorption and urinary excretion of oxalate. It is concluded that hyperoxaluria in JIB patients is due to a significant extent to hyperabsorption of oxalate. PMID- 2595325 TI - Percutaneous renal and ureteric stone extraction. Report on the first 500 operations. AB - A consecutive series of the first 500 percutaneous renal and ureteric stone extractions in 451 patients was analysed. During the period studied, percutaneous extraction was offered to all patients with conventional indication for stone removal except a few, very early ureteric stone patients in whom open lithotomy was carried out. Ureteroscopy and extracorporeal shock wave lithotripsy had not come into routine use. Four hundred and seventy-eight stone operations (96%) could be performed by the percutaneous route; early in the series, 21 open operations and one transurethral Dormia basket extraction were performed, mainly because of failed mobilisation of ureteric stones (12 patients) or various peroperative complications (9 patients). The target stones were completely removed in 88% of all percutaneous procedures, with the best results in the largest group of patients with 6-20 mm solitary stones or 2-3 stones less than or equal to 10 mm. Stones in the ureter and pelvi-ureteric junction without any other concomitant stones were all completely removed. Bleeding was the most frequent peroperative complication. No kidney was lost. An 84-year-old man died of intercurrent disease postoperatively. PMID- 2595328 TI - Spontaneous rupture of the urinary bladder--a late complication to radiotherapy. Case report. AB - Spontaneous rupture of the urinary bladder is extremely rare. A case of spontaneous intraperitoneal rupture of the urinary bladder 18 years after radiation therapy for testis cancer is reported. PMID- 2595326 TI - Repeated application of EMLA cream 5% for the alleviation of cannulation pain in haemodialysis. AB - The analgesic effect and the occurrence of local reactions after repeated application of a lidocaine/prilocaine cream (EMLA 5%) were investigated in 31 haemodialysis patients. The cream was used for alleviation of cannulation pain prior to the haemodialysis (HD) for a period of 1-1.5 years. In each patient 300 to 312 applications of the cream were made during the period. Local skin reactions were recorded after the cream applications and the analgesic effect was evaluated with double-blind, crossover placebo controls at regular intervals. Seventeen patients completed the study. EMLA gave considerable pain relief and was significantly better than placebo at all effect evaluations but one. The frequency of local reactions was low and not correlated to the number of applications of EMLA. Two patients, however, interrupted their treatment due to local irritation. PMID- 2595327 TI - Transurethral, transprostatic incision of a seminal vesicle cyst. Case report. AB - Cystic lesions of the seminal vesicle are rare. We report on a new technique of transprostatic incision of a seminal vesicle cyst, which was used successfully in a patient with recurrent cyst 7 years after transrectal aspiration. PMID- 2595329 TI - Intravesical lidocaine in severe interstitial cystitis. Case report. AB - We report on a patient with a 2-year history of severe interstitial cystitis with disabling symptoms of painful urgency and urinary incontinence. The condition is characterized by a severe inflammatory reaction in the cystic wall and varying degrees of success for most therapeutic measures employed. Repeated vesical instillations of lidocaine in the urinary bladder relieved the patient from her pain and induced a long-lasting and potent anti-inflammatory effect on the cystic wall. Plasma lidocaine concentrations were below toxic levels and no adverse reactions were reported. PMID- 2595330 TI - Spontaneous rupture of the kidney: a cause of acute abdominal pain. Case report. AB - We report on 5 patients who presented with acute onset of abdominal pain, a palpable mass, and a rapid decrease in hemoglobin. All 5 patients had been entirely free of urological symptoms until shortly before hospitalization. Spontaneous rupture of a kidney with an underlying pathological condition was found in all cases. In 2 cases the underlying lesion was renal cell carcinoma, while in the other 3 cases the lesion was a renal angiomyolipoma, a polycystic kidney and hydronephrosis secondary to UPJ obstruction, respectively. The importance of considering the possibility of spontaneous rupture of the kidney in the evaluation of cases of an acute abdomen is stressed. PMID- 2595331 TI - Acute renal failure caused by low-osmolar radiographic contrast media in patients with diabetic nephropathy. AB - Four patients reacting with acute renal failure despite using low osmolar contrast media are reported. They all had diabetic nephropathy and renal insufficiency. A retrospective study of 75 consecutive patients examined with angiography showed that 13% had both of these two risk factors. PMID- 2595333 TI - Epidemiology of rheumatoid arthritis and of its treatment. Proceedings of a meeting. Hannover, West-Germany, 16-18 October 1988. PMID- 2595332 TI - Myelolipoma of the adrenal gland. Case report. AB - Myelolipoma is a rare, benign, endocrinologically nonfunctioning adrenal tumor composed of fatty tissue with foci of hematopoietic cells. Clinical diagnosis and surgical removal are extremely rare. We report a case of large myelolipoma (10 x 6 x 6 cm) that was removed surgically in a 54-year-old man in whom the mass was studied preoperatively by sonogram, CT and angiography. PMID- 2595334 TI - Rheumatoid arthritis as seen from official data registers. Experience in Finland. AB - Computerized public data registers are an important data base for bodies monitoring public health. They can also be used for epidemiological research. The main problems in the use of the registers are administrative and qualitative. The use, and especially the linking of different registers together, is strictly regulated by law. The trend seems to be towards more strict regulations. Another problem is the quality of the data. The registers were designed for administrative purposes and therefore, the classification of data is not always suitable for research. In addition, errors are possible at several stages of the production and filing of the data. International comparisons are difficult because of differences in legislation and administrative rules. However, despite these problems, public data registers are an important resource for research, and their importance will grow with time and improvements in the quality of the registers. PMID- 2595335 TI - Are there secular trends in the occurrence and severity of rheumatoid arthritis? AB - There are considerable research and health service benefits in understanding current trends in a disease as common and as severe as rheumatoid arthritis. Unfortunately in the absence of both a high and constant case fatality rate and a population based morbidity registration system, there is no direct means of assessing changes in incidence in contrast, for example, to the situation with cancer. All the available data are inadequate and subject to considerable bias. It is of note however that all the available data are relatively consistent in pointing to a recent reduction in incidence over the last two decades coupled with a decrease in case severity. The immediate problem remains therefore to set up a true population based recording system which will permit the identification of trends both of incidence and severity. It should not be necessary for this to be established nationwide and a study area within a country could be chosen providing its population was representative and of sufficient size. For the latter a minimum seize of 500,000 persons would be needed. PMID- 2595336 TI - Early arthritides: nosography, nosology, and diagnostic criteria. AB - Follow-up studies of patients with early arthritides are sparse and they are usually restricted to certain diagnostic groups. Therefore 141 unselected patients suffering from arthritis since no more than 12 months were entered into a prospective study. The largest group (n = 57, 40%) consisted of patients with definite rheumatoid arthritis. Forty individuals (28%) were judged to have undifferentiated arthritis since they could not be classified according to established diagnostic criteria initially. After 9 +/- 3 months mean follow-up only 21 of 45 patients (47%) fulfilling criteria for definite rheumatoid arthritis at the onset of the study remained in this category, 9 (20%) still suffered from arthritis but they met less than 5 ARA criteria, and 15 (33%) went into remission. Among 50 patients with undifferentiated arthritis or spondylarthropathy an even smaller proportion of 16 individuals (32%) still had arthritis, which could not be classified, whereas 34 (68%) showed no signs of persisting peripheral arthritis. Thus, criteria diagnoses are inadequate for the selection of the patients at the onset of the disease since they are frequently false positive and they omit other arthritides important for differentiation. Further disadvantages of criteria diagnoses are evident: they imply a large spectrum of manifestations of the disease, they overlap with other entities, they do not provide sufficient information regarding the prognosis and adequate treatment. To improve the prognostic value of a nosological classification a concept of descriptive diagnoses is discussed. PMID- 2595337 TI - Oral contraceptives and the risk of rheumatoid arthritis: the great transatlantic divide? PMID- 2595338 TI - Activity and severity of rheumatoid arthritis in Hannover/FRG and in one regional referral center. AB - Between November 1984 and July 1988 a total of 8044 randomly selected German residents of the city of Hannover/FRG, aged 25 to 74, have been screened for rheumatic complaints by means of a postal questionnaire. An average 87% of the probands contacted returned completed questionnaires. Respondents with a "positive" questionnaire, i.e. suggestive of the existence of an inflammatory joint disease were invited for a rheumatological examination at the Hannover Medical School. 72% participated. 45 of a total of 1291 participants were identified as suffering from active or inactive, mostly rheumatoid arthritis. This yields a minimum prevalence of 0.56% (+/- 0.19%). The true prevalence is estimated to be 0.91% (99%-confidence interval 0.64-1.18). In 1985 and 1986 103 German RA sufferers aged 25 to 74, all citizens of Hannover, were referred to our outpatient rheumatology clinic for a first consultation. A comparison between the two groups revealed a higher disease activity in terms of "objective" criteria (joint swellings, ESR, rheumatoid factor) in the group of the referred patients as opposed to RA suffers from the community. Both groups were comparable in respect to "subjective" symptoms (morning stiffness, joint pain, pain intensity), functional capacity and degree of erosive joint lesions. The rheumatological outpatient clinic at the Hannover Medical School, providing the only specialized service in the region, actually covers less than 20% of all RA sufferers within the municipal area of Hannover and less than 50% of those with a "classical" RA according to the ARA-criteria. PMID- 2595339 TI - Course and prognosis of early rheumatoid arthritis. AB - Lessons learned from a 20 year prospective study of 100 Rheumatoid Arthritis (RA) patients are considered. Forty six had died and the causes of death are discussed and correlations with early features; the findings in the survivors and the patterns of the course of arthritis and treatment are described. A loss of life expectancy was observed: the 9 patients whose deaths were due to RA or its systemic complications, died some 15 years prematurely; the 8 in whom RA contributed to death died some 10 years prematurely and in the 29 in whom death was unrelated to RA, death was premature by about 5 years. Already after 1 year of arthritis the functional capacity was reduced in those patients who later died due to RA or in whom RA or its treatment contributed to death. The men died earlier than the women and overall mortality in men was higher despite a younger age at onset. Patients with persistently high ESR and strong seropositivity for rheumatoid factor also did badly. Of the patients, who had died, the functional capacity at last review before their deaths was noted. It appears that already 1 8 years before their deaths 35% of the patients were confined to chair or bed (Steinbrocker grade IV) and 24% markedly restricted (grade III). These figures show that prognosis of RA patients referred to a rheumatologist is probably worse than generally suggested. Rheumatoid arthritis is a severely disabling and potentially lethal disease. PMID- 2595340 TI - Highlights in methodology and current experience with tenoxicam. PMID- 2595341 TI - Highlights in methodology and current experience with tenoxicam. Proceedings of a satellite symposium and poster presentation at the Vth EULAR Symposium. Paris, France, 10-12 November 1988. PMID- 2595342 TI - New diagnostic tools and methodological approaches: an outlook to the future. AB - In spite of recent progress, the aetio-pathogenesis of a large number of osteoarticular diseases is as yet not well known. This is apparent for commonly occurring diseases such as osteoarthritis (OA), rheumatoid arthritis (RA), type I osteoporosis (post-menopausal) and type II osteoporosis (senile). As a result of the lack of knowledge about these pathogenic factors, therapeutics often remain symptomatic and not completely satisfactory. Nowadays there is a need for methodological tools to explore the causes or pathogenic factors of these conditions. Moreover, in OA, there is at present no way to predict the development of this disease and to follow its evolution, hence, there is a need for specific markers. These biological and methodological developments are useful for searching for new molecules able to compensate for the pathogenic anomalies demonstrated in RA and OA. In this paper, we will discuss some of the methodological developments now in progress which may provide solutions to some of the aetiopathogenic, diagnostic and therapeutic problems related to RA and OA. PMID- 2595343 TI - Tenoxicam milk formulation in the treatment of rheumatic conditions. AB - Tenoxicam milk formulation is a new galenical form of a non-steroidal anti inflammatory drug (NSAID). It is especially suitable for patients having compliance problems or difficulty in swallowing tablets. This formulation has proved to be a useful alternative oral treatment in various rheumatic conditions. Combining rapid onset of action and maintenance of active plasma levels, tenoxicam achieved good clinical efficacy and tolerability in the vast majority of the patients studied. PMID- 2595344 TI - Tenoxicam used as a parenteral formulation for acute pain in rheumatic conditions. AB - Tenoxicam is a thienothiazine derivative with marked analgesic and anti inflammatory activities. The parenteral application of tenoxicam is especially suitable for initial therapy in acute and painful rheumatic conditions. The pharmacokinetic behaviour of tenoxicam after i.m., i.v. and p.o. administration did not differ, with the exception that higher plasma concentrations were reached during the first two hours after the parenteral dose. After both i.m. and i.v. application, tenoxicam showed a rapid onset of action, and reliable improvement of pain status. Tenoxicam was well tolerated both systemically and locally. About 10% of all patients experienced adverse events characteristic of non-steroidal anti-inflammatory drugs (NSAIDs). PMID- 2595345 TI - A comparison of the effects of tenoxicam and piroxicam on grip strength in patients with rheumatoid arthritis. AB - Ten patients were recruited for this randomised double-blind pilot study to compare the efficacy and tolerance of tenoxicam 20 mg daily and piroxicam 20 mg daily in patients with rheumatoid arthritis (RA). The change in grip strength over an eight week study period was the primary efficacy variable and measurements were made using a digital pinch/grip analyser (MIE Medical Research Ltd.). There were no significant treatment differences in the change in grip strength (p greater than 0.2), although greater improvements in all efficacy parameters measured were achieved for patients receiving tenoxicam than those receiving piroxicam. Both treatments were well tolerated with few adverse events reported. Further studies with more patients are required to adequately assess whether there are any differences between treatments. PMID- 2595346 TI - Backward tilting of the posterior atlantal arch in rheumatoid arthritis. AB - In a retrospective survey of 450 patients with rheumatoid arthritis on whom cervical spine radiography was performed, one patient was found with a backward tilting of the posterior arch of the atlas. With preserved relations anteriorly, the posterior arch was rotated downward in front of the spinous process of the axis, encroaching on the space of the spinal canal. PMID- 2595347 TI - Alteration of mitogenic responses of mononuclear cells by anti-ds DNA antibodies resembling immune disorders in patients with systemic lupus erythematosus. AB - Anti-double-stranded DNA antibodies (anti-DNA) purified from pooled active SLE sera by lambda phage DNA-affinity chromatography was found to affect phytohemagglutinin (PHA) and pokeweek mitogen (PWM)-induced responses of normal mononuclear cells. Anti-DNA at a concentration of 0.25 mg/ml (equivalent to 21 units/ml of DNA binding activity) significantly suppressed the PHA-induced [3H]thymidine incorporation of mononuclear cells in 3 days of culture but had no effect on 5-day and 7-day cultures. In contrast, a biphasic effect of anti-DNA on PWM response was found such that early phase (3-day culture) was inhibited whereas late phase (from 5 days to 9 days of culture) was enhanced by the antibodies. Anti-DNA also increased the immunoglobulin synthesis by PWM stimulated B cells. The inhibition of PHA response in 3-day culture by anti-DNA is not due to changes in T cell subpopulations. Because interleukin 1 (10 units/ml) could restore the PHA response, it appears that anti-DNA suppressed the IL-1 production by monocyte/macrophage. The biphasic effect of anti-DNA on PWM response is the result of monocyte impairment and B cell stimulation by the antibodies. In the early phase (on day 3) the inhibition would seem to be due to impairment of accessory cell function by anti-DNA, though in late phase (after day 5) the anti-DNA may stimulate B lymphocytes to incorporate more thymidine in the presence of PWM. These biological effects of anti-DNA in vitro resemble the in vivo immunologic disorders in patients with SLE, in that impaired cell mediated immunity and B cell hyperactivity are frequently observed. PMID- 2595348 TI - Clinical neurological, electrophysiological, and cerebral CT scan findings in systemic lupus erythematosus. AB - Thirty SLE patients underwent clinical neurological examination, electrophysiological studies, cerebral computer tomographic (CT) scans, and blood sampling. Nineteen patients (63%) had clinical neuropsychiatric and 10 patients (33%) had clinical neuromuscular manifestations. Migrainous headache affecting 11 patients (37%) was the most prevalent clinical manifestation. Electrophysiological testing revealed abnormal electroencephalography in 10 patients (33%). Abnormal electromyography and nerve conduction velocity were found in 13 (43%) and 7 (24%) patients respectively. Abnormal visual evoked response was detected in 2 patients. Cerebral CT scans displayed cerebral atrophy in 20 patients (71%), while 6 patients (21%) had cerebral infractions. Disease activity assessed by two different tests revealed a higher prevalence of cerebral infarctions, classical migraine, muscular weakness, and pathological electromyography and nerve conduction velocity in the higher disease activity groups. Cerebral infarctions were only found among anti-Ro negative patients, but apart from this, no significant association could be found between coagulopathy, circulating immune complexes, cryoglobulins, routine immunological tests, medication, and any clinical, electrophysiological or cerebral CT pathology. PMID- 2595350 TI - Increased EMG activity during short pauses in patients with primary fibromyalgia. PMID- 2595349 TI - Computerized assessment of radiological changes of the hand in rheumatic diseases. AB - Evaluations of radiological changes in rheumatic diseases are subject to great inconsistency. In this study, digital image analysis is shown to be a promising tool in the evaluation of joint space narrowing. The repeatability of the measurements is shown to be better than that of manual methods and is also less dependent on the observer. PMID- 2595351 TI - The value and significance of magnetic resonance imaging of the craniocervical junction in rheumatoid arthritis. Consequences for therapeutic approaches. PMID- 2595352 TI - Serum gastrin, fasting and after stimulation, in systemic sclerosis. PMID- 2595353 TI - Membership: it is a question of dollars and sense. PMID- 2595354 TI - Risk management for physicians. Duty of physician to testify in court for his injured patient. PMID- 2595355 TI - AZT and asymptomatic HIV infection. PMID- 2595356 TI - [Effect of wind and temperature on concentrations of Pb in urban air. I. Example of a location situated under the direct influence of intense traffic]. AB - A simple mathematical relationship has been established between the Pb concentrations in the ambient air in the vicinity of a heavy-traffic road and some meteorological parameters (wind speed and direction, temperature). The application of this relationship permits the interpretation of the variations in concentrations with respect to the time of day and period of the year. PMID- 2595357 TI - Use of Polytrichum formosum (moss) as a passive biomonitor for heavy metal pollution (cadmium, copper, lead and zinc). AB - After sampling over regular intervals from 1985 to 1987 the heavy metals Cd, Cu, Pb and Zn were quantitatively determined by atomic emission spectrometry/inductively coupled plasma in above-ground parts of the moss Polytrichum formosum (Hedw.). All metals present a typical summer-winter oscillation (seasonal variation), which is much greater than the "inter-stand" variation of Polytrichum formosum within the forest ecosystem under investigation. To obtain comparable results on a regional or global scale it is suggested to collect all samples of Polytrichum formosum for biomonitoring purposes in the last week of September. PMID- 2595358 TI - ADA deficiency treatment. AB - In the report "X-ray diffraction to 302 giga-pascals: High-pressure crystal structure of cesium iodide" by H. K. Mao et al. (3 Nov., p. 649), reference 10, to a paper by R. Reichlin et al. [Phys. Rev. Lett. 56, 2858 (1986)], was incorrectly numbered (9) in the text (p. 649, column 3, line 1; p. 650, column 1, line 49). PMID- 2595359 TI - Street-wise crack research. PMID- 2595360 TI - British rabbits: scholarship down. PMID- 2595361 TI - Many gene changes found in cancer. PMID- 2595362 TI - Making new materials with nature's help. PMID- 2595364 TI - Neuroscience at Washington University. PMID- 2595363 TI - The Molecule of the Year. PMID- 2595365 TI - Ethics and USGS. PMID- 2595366 TI - Britain's Lords debate embryo research. PMID- 2595367 TI - Science and PR north of the border. PMID- 2595368 TI - New AIDS drugs take careful aim. PMID- 2595369 TI - Key piece found for immunology puzzle? PMID- 2595370 TI - Volatilization of high molecular weight DNA by pulsed laser ablation of frozen aqueous solutions. AB - DNA has been volatilized by pulsed laser ablation of a thin film of a frozen aqueous DNA solution. The target film was irradiated in vacuum by a pulsed laser at power densities sufficient to ablate the ice matrix. The expanding ablated water vapor entrained embedded DNA molecules and expelled them into the gas phase. Ejection of DNA molecules as large as 410 kilodaltons was verified by collection of the ablation products and subsequent mass analysis by polyacrylamide gel electrophoresis with autoradiographic detection. PMID- 2595371 TI - A model of human acute lymphoblastic leukemia in immune-deficient SCID mice. AB - A human acute lymphoblastic leukemia (ALL) cell line that was transplanted into immune-deficient SCID mice proliferated in the hematopoietic tissues, invaded various organs, and led to the death of the mice. The distribution of leukemic cells in SCID mice was similar to the course of the disease in children. A-1 cells marked with a retrovirus vector showed clonal evolution after the transplant. SCID mice that were injected with bone marrow from three patients with non-T ALL had leukemic cells in their bone marrow and spleen. This in vivo model of human leukemia is an approach to understanding leukemic growth and progression and is a novel system for testing new treatment strategies. PMID- 2595373 TI - Newer strategies in the management of thrombotic disorders: II. PMID- 2595374 TI - Thrombectomy, lysis, or heparin treatment: concurrent therapies of deep vein thrombosis: therapy and experimental studies. PMID- 2595372 TI - Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation. AB - One action of cyclosporin A thought to be central to many of its immunosuppressive effects is its ability to inhibit the early events of T lymphocyte activation such as lymphokine gene transcription in response to signals initiated at the antigen receptor. Cyclosporin A was found to specifically inhibit the appearance of DNA binding activity of NF-AT, AP-3, and to a lesser extent NF-kappa B, nuclear proteins that appear to be important in the transcriptional activation of the genes for interleukin-2 and its receptor, as well as several other lymphokines. In addition, cyclosporin A abolished the ability of the NF-AT binding site to activate a linked promoter in transfected mitogen-stimulated T lymphocytes and in lymphocytes from transgenic mice. These results indicate that cyclosporin A either directly inhibits the function of nuclear proteins critical to T lymphocyte activation or inhibits the action of a more proximal member of the signal transmission cascade leading from the antigen receptor to the nucleus. PMID- 2595375 TI - A new mechanical device for the prevention of thrombotic problems in microsurgery. PMID- 2595377 TI - Attention and learning in infancy: investigative and clinical issues. PMID- 2595376 TI - Oncologic emergencies. PMID- 2595378 TI - C-reactive protein as a diagnostic tool. PMID- 2595379 TI - Sudden death from primary lung abscess in middle-aged diabetic men--two case reports. AB - We describe the course of illness in two middle-aged diabetic men who died suddenly from primary lung abscesses. They were in apparent good health and presented with fever, cough and small lung abscess [less than 5 cm] on chest radiographs. While receiving standard antimicrobial therapy in hospital, they experienced sudden respiratory arrest from aspiration of purulent material presumably following the drainage of lung abscess contents. This is a very unusual complication and the similar clinical features between these two cases prompted this report. PMID- 2595380 TI - Normal menstruation in a case with many of the morphological features of Turner's syndrome--an unusual manifestation. AB - A case is reported of normal menstruation in a patient with many of the morphological features of Turner's syndrome. PMID- 2595381 TI - Malfunction of Tenckhoff catheter due to a rare kink. AB - A case of sudden malfunction of Tenckhoff Catheter in a patient undergoing continuous ambulatory peritoneal dialysis (CAPD) treatment is reported. Upon laparotomy, the catheter was found to form a knob inside the peritoneal cavity. The report emphasized on the simple but effective diagnostic value of abdominal X ray and the importance of care of the bowel motion in a patient on CAPD. PMID- 2595382 TI - Evoked potentials and Doppler vascular studies in hydranencephaly. AB - A study of brainstem auditory evoked potentials, electro-encephalography and doppler vascular scans were conducted in an infant with hydranencephaly. The abnormalities detected were consistent with the gross cerebral cortical anomaly in hydranencephaly. PMID- 2595383 TI - Trends in coronary heart disease mortality in Singapore. PMID- 2595384 TI - The acquired immunodeficiency syndrome in Singapore--epidemiological perspectives. AB - The Acquired Immunodeficiency Syndrome (AIDS) is caused by a retrovirus, the Human Immunodeficiency Virus (HIV). As at 30 April 1988, there were 22 infected individuals in Singapore, of which 4 had AIDS. A comprehensive retrospective study was carried out to establish the clinico-epidemiological features of the disease and its transmission in Singapore. The infected patients have been related mainly to sexual transmission through sexual contact (homosexual, bisexual or heterosexual) with men and women from countries where HIV infection is more prevalent. The majority of the infected were homosexual males in the age range 20-39 years. There was one case of transfusion-associated AIDS and another was infected through heterosexual transmission. The local pattern is consistent with the Western pattern (Pattern 1), with the notable absence of intravenous drug abusers, paediatric cases or infected haemophiliacs. PMID- 2595385 TI - Chronic inflammatory bowel diseases in Singapore. PMID- 2595386 TI - Prevalence of hepatitis delta virus infection in Malaysia. AB - The prevalence of coinfection, superinfection and chronic infection with the hepatitis delta virus (HDV) was studied in 324 hepatitis B surface antigen (HBsAg)-positive Malaysians. Of these, 10.0% (5/50) had coinfection, 5.7% (11/194) had superinfection, but none of the 80 patients with chronic liver disease (CLD) or primary hepatocellular carcinoma (PHC) had chronic infection with HDV. The overall HDV infection was 4.9% (16/324). One of the coinfection cases acquired the HDV infection as early as 1982. HDV superinfection was detected mainly among IV drug abusers (20% or 7/35) and promiscuous males and females (13.6% or 3/22). They were all asymptomatic. Only 0.8% (1/125) apparently healthy blood donors was infected with HDV. None of the 12 multi-transfused patients examined were positive. Malaysia is the only Southeast Asian country examined so far in which HDV infection was detected. The reason could be that the IV drug abusers and the sexually promiscuous groups missed being examined in the other countries. Comparing the HDV infection rates in 4 categories of infected Malaysians (viz. acute hepatitis B patients, IV drug abusers, blood donors and CLD patients) with those of other countries, it was noted that the Malaysian rates were similar to the lowest in the range of prevalence rates of each category in the latter group. The rate of coinfection in a preliminary study in 1982-84 (9.0% or 1/11) was not very different from that obtained to date (10.0% or 5/50).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2595387 TI - Characteristics of geriatric admissions to two medical departments in Singapore. AB - A survey was conducted to study certain characteristics of geriatric patients admitted to two medical departments in Singapore. The aim was to create awareness as well as to provide a better understanding of these elderly as more and more doctors would have to attend to them. Our results show that about 27% of admissions were geriatric patients. The typical geriatric patient in this study was about 75 years old (mean age 74.6 years) and was likely to present with breathlessness due to heart disease or pneumonia. The overall duration of stay in hospital was 10 days and only about 6% of the patients had "discharge" problems needing assistance from the Medical Social Worker. About one in five patients died in hospital, usually from pneumonia or ischaemic heart disease. PMID- 2595388 TI - Psychological distress of families caring for the frail elderly. AB - In a study of psychological problems in 60 principal family carers of elderly patients, 12 (20%) were found to experience mild depression or anxiety. There was no significant difference in psychological distress between male and female carers, and between carers in the two age groups, 20-49 years and 50 years and above. Those carers who lacked social support had a greater propensity to develop anxiety or depression, but there was no association between psychological distress of carers and functional disabilities of the elderly patients. PMID- 2595389 TI - Percutaneous ultrasonic lithotripsy--its role in the management of renal and upper ureteric stones. AB - Percutaneous ultrasonic lithotripsy (PUL), a new technique used in the treatment of renal stones has been shown to be safe and effective with low morbidity. 54 of the 57 patients (95%) were successfully treated by this method and all were done as a single stage procedure. 39 patients (68%) in this series were either unsuitable or had failed extracorporeal shock wave lithotripsy (ESWL). No mortality occurred in this series and one patient with staghorn stone required a nephrectomy due to severe secondary haemorrhage. Though PUL is technically more difficult to perform, it is a better alternative than open renal surgery and is complementary to ESWL especially in the treatment of the more complicated renal stones. PMID- 2595390 TI - Wertheim's operation--a study of 130 cases. AB - The Hsu's method of radical hysterectomy and lymphadenectomy procedure is a modification of the Okabayashi's radical hysterectomy. It involves the creation of the pararectal and paravesical spaces completely down to the pelvic floor and the excision en block of the uterus with its appendages, the parametria and the entire cardinal ligaments and the upper 1/3 to 1/2 of the vagina with its paracolpia. The vagina is lengthened by the Hsu's technique of suturing the vagina with a Boston suture incorporating the cut margin of the rectal serosa to the posterior rim of the vagina and stitching the visceral peritoneum 2 cm above the cut margin of the rectal serosa. The ovaries are preserved in young patients. Lymphadenectomy involves the dissection of the anterior and posterior chains of the common iliac nodes, the external iliac, obturator, internal iliac and presacral nodes. The author having been trained in the Hsu's method of radical hysterectomy by Professor Hsu himself, conducted a prospective study of the morbidity, sequelae and survival rates of this operation in Singapore. Between January 1982 and July 1987, 130 cases of cancer of the cervix were operated on by the author. Patients who had lymph node metastasis or parametrial infiltration were given adjuvant post operative irradiation. Every patient was followed up personally by the author. Only six patients were lost to follow-up at varying times after operation. Four cases were excluded from analysis. Of the remaining 126 cases, 67 were stage 1B, 20 stage 2A, 36 stage 2B, 2 were central recurrences following radiotherapy and one corpus cancer stage 2. Eleven patients (8.7%) had operative or post-operative morbidity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2595391 TI - An epidemiological study of pityriasis rosea in Middle Road Hospital. AB - Pityriasis rosea is a common skin disorder seen in dermatological practices. A one year prospective study on pityriasis rosea was carried out in Middle Road Hospital, Singapore. A total of 214 patients were studied. The incidence rates by age, sex and month were analysed. The peak incidence was in the 20-24 age group. There was a male predominance. More patients with pityriasis rosea were seen in the months of March, April and November. The clinical features in our patients concur with other studies. Blood for VDRL was done on 170 patients. Two had a biological false positive test. Total white counts were normal in 97.9% of specimens done. The rash lasted from 1 to 8 weeks in 84.4% of the patients with most patients suffering from the rash for 5 weeks. PMID- 2595392 TI - Conservation breast treatment: a viable option locally. AB - Conservation treatment in carcinoma of the breast is a viable option in the West but is still an uncommon practice locally. Many reasons have been put forth, including the late stage of the tumour we see and the small breast size. This paper presents 25 cases treated by lumpectomy and irradiation with satisfactory cosmetic results, although the follow-up period is short. The introduction of this technique may encourage women to seek treatment earlier, without the fear of losing their breasts. PMID- 2595393 TI - Psychiatric complications of Erimin abuse. AB - Nimetazepam (Erimin) is a benzodiazepine which has become a new drug of abuse in Singapore. Three cases presenting with psychiatric complications had been treated as inpatients over a period of one and a half years (1986 to 1987) in Woodbridge Hospital and Tan Tock Seng Hospital. Their clinical presentations which included drug dependency, withdrawal psychosis and transient drug psychosis are described and discussed. PMID- 2595394 TI - Prosthodontic management of maxillofacial defects after cancer surgery. AB - Surgery for maxillofacial cancer often creates a defect, which may affect speech, swallowing, mastication and facial appearance. The provision of a prosthesis is one method to help restore these physiologic and psychologic functions. Prosthodontic planning and rehabilitation should be an integral part of the team management to provide not just the preservation, but a quality of life for the patient. Various types of appliances are illustrated and the role of the dental surgeon is emphasised. PMID- 2595395 TI - The outcome of inflammatory bowel disease. PMID- 2595396 TI - Vasomotor rhinitis--atrophic rhinitis: two ends of an autonomic spectrum. AB - A hypothesis is put forward based on clinical observations and treatment modalities in vasomotor non-allergic rhinitis (V.M.R.) and primary atrophic rhinitis (P.A.R.). The hypothesis postulates that (1) V.M.R. and P.A.R. are two diseases at the ends of an autonomic spectrum (2) The anterior nasal aperture, its dimensions and sensory receptors play a vital role in the etiopathogenesis of both the conditions through reflex autonomic action. PMID- 2595398 TI - [Nursing research--about mothers and fathers and many small infants]. PMID- 2595397 TI - Cutaneous metastases--an uncommon and unusual mode of presentation of gastric carcinoma. AB - Cutaneous and oral mucosal metastases from gastric carcinoma are very uncommon. It is even more uncommon and unusual to have a patient with gastric carcinoma whose mode of presentation is that of "skin nodule" (cutaneous metastases). We report one such patient, who was first seen in a skin clinic, then in a dental clinic, and finally was referred to a medical clinic. Current literature on cutaneous metastases of gastric carcinoma is reviewed in this case report. PMID- 2595399 TI - [Nursing research--about pressure sores]. PMID- 2595400 TI - [Nursing research--on obesity and eating behavior]. PMID- 2595402 TI - [Nursing research--on people with dementia disorders]. PMID- 2595401 TI - [Nursing research--on ethical problems in health and nursing care]. PMID- 2595403 TI - [Developments in health care research raises expectations]. PMID- 2595404 TI - [FoU (research and development) within the nursing field--activity which increases in intensity]. PMID- 2595405 TI - [Videofluoroscopic studies of the swallowing process in children with cerebral palsy]. AB - The swallowing problems of cerebral palsied children are clinically evaluated by means of subjective criteria. Little research has been done to analyse these problems objectively and scientifically. The aim of this study was to analyse the swallowing patterns of cerebral palsied children in two age groups by means of videofluorography. Ten cerebral palsied children between the ages of four and thirteen years were selected as subjects. During the investigation they were asked to swallow a liquid and certain aspects of the oral preparatory, oral and pharyngeal phases of swallowing were analysed. The results of the study indicated that swallowing problems do occur in cerebral palsied children, mainly during the oral phase, and in some cases take on the form of inadequate contact between the tongue and palate and poor control of the bolus. The group of younger children had more swallowing problems than the older group. In the former group the type of cerebral palsy did not seem to play any role in the swallowing problems which occurred while in the older group there were indications that the type of cerebral palsy could possibly play a role. The results of the study indicate that videofluorography can be implemented effectively to scientifically evaluate the swallowing problems of cerebral palsied children. PMID- 2595406 TI - Communicative competence in a group of visually impaired children. AB - Aspects of verbal and non-verbal communicative competence of five visually impaired six and seven year old children were investigated. The Profile of Communicative Appropriateness (Penn, 1983) was used to assess communicative competence in one discourse interaction with a known interlocutor (mother). The results indicated that the subjects were predominantly appropriate in terms of verbal communication, and predominantly inappropriate in terms of non-verbal communication. Severity of visual impairment influenced performance in terms of non-verbal communication. Research and therapeutic implications are discussed. PMID- 2595407 TI - [The influence of certain contextual factors on voice onset time, vowel duration and utterance duration in verbal apraxia]. AB - The concept of context sensitivity as borrowed from the coalition model has important implications for the interpretation of the symptoms of apraxia of speech and for a better understanding of the nature of the disorder. In this study which was part of the wider investigation into the effect of variation in contextual factors on apraxia of speech (van der Merwe, Uys, Loots and Grimbeek, 1987; 1988), the effect of two contextual factors namely sound structure and articulatory features on voice onset time, vowel duration and utterance duration was acoustically analysed. Four subjects with acquired apraxia of speech and one with developmental apraxia of speech were tested. Findings indicated that voice onset time is not context sensitive. Errors in voice onset time were not true substitutions with voiceless sounds but were inconsistent distortions due to an inability to keep interarticulator synchronization within the critical temporal boundaries of motor equivalence. Vowel and utterance duration were found to be context sensitive. The deviation in duration increased with increased complexity of the utterance. As was the case with the auditorily perceived symptoms, the temporal characteristics of apraxia of speech can also be classified into core symptoms and associated symptoms based on their context sensitivity. PMID- 2595408 TI - Segmental speech timing at the phoneme and syllable levels in English and Afrikaans speaking white South African children. AB - Two aspects of segmental timing were acoustically measured in the speech production of 30 English and 30 Afrikaans speaking white South African children. These were VOT and medial stop closure duration in VCV nonsense syllables. In addition, medial vowel duration in CVC nonsense syllables was measured in English speakers. Comparisons were made between younger (mean age 4.25 years) and older (mean age 6.5 years) subjects in each language group. Graphical statistical methods revealed certain trends in the data. English speakers employed short- and long-lag VOT for voiced and voiceless stops while Afrikaans speakers used two short-lag categories. Contextually determined right-to-left timing effects were identified which were in agreement with the literature, with different rates of acquisition of medial stop closure duration rules being observed between the language groups. PMID- 2595409 TI - A preliminary investigation of the pragmatic abilities of a group of language disordered children. AB - The communicative acts, conversational acts, and breakdown repair abilities of six language-disordered children with a syntactic age of +/- 3 years old as determined by the LARSP (Crystal, Fletcher, Garman: 1976) were investigated. Sampling of each subject involved two separate naturalistic interactions with a familiar adult and a language disordered peer. The data obtained from the transcriptions were analysed in terms of linguistic and nonlinguistic behaviours on the Communication Profile by Wollner and Geller (1982). Specific patterns of deficit and strengths were observed and these trends were related to recent literature in this area. The study emphasises that there is as much heterogeneity in the pragmatic skills as in the other communication skills of language disordered children, although this is due to some extent to the limitations of assessment in naturalistic settings. It also indicates individual areas of pragmatic deficit that require remediation. PMID- 2595410 TI - Single case experimental designs: an essential service in communicatively disabled care. AB - A situation analysis of communication disabilities of and services to this population in the RSA reveals a lack of knowledge about the field and a paucity of research, probably due to therapists' extreme involvement in clinical practice. In this article the advantages of single case experimentation are put forward and specific designs are discussed in an attempt to motivate and enable clinicians to be producers of research. It is pointed out that this type of research will not only add valuable scientific information to the field of speech pathology and audiology, but it will also increase accountability in clinical practice. PMID- 2595411 TI - Language intervention at schools: changing orientations within the South African context. AB - The role of the speech therapist in the school has changed drastically over the last decade. The reasons for these changes originate from a growing realisation of the importance of contextualising intervention within a particular community. This article aims at providing an analysis of the present school population in South Africa with specific reference to the Black schools as a basis for discussion on the role of the speech and language therapist within this context. The problems of second language learning and teaching are highlighted and the role of the language therapist as a consultant within the Black school system is emphasized. PMID- 2595413 TI - Accountability of pain control programs in the United States. PMID- 2595412 TI - The constant star. PMID- 2595414 TI - Sisyphus tantalized: a corrigendum. PMID- 2595415 TI - Ingestion of prescription drugs by children: an epidemiologic study. AB - Although the Poison Prevention Packaging Act of 1970 has resulted in a 65% decline in ingestion of products packaged in child-resistant containers, ingestion of prescription drugs by children has declined by only 36%. Since ingestion of solid prescription drugs remains an important cause of ingestion related morbidity in children, this descriptive epidemiologic study of cases reported to a poison control center was done with the hope of identifying factors responsible for this continuing problem. The study provides an epidemiologic perspective of this unnecessary risk to child health, and also proposes interventions targeted to high-risk caregivers. PMID- 2595416 TI - Pleural effusion: comparison of clinical judgment and Light's criteria in determining the cause. AB - Pleural fluid analysis is often the initial diagnostic test used to determine the cause of a pleural effusion. We prospectively studied 33 consecutive patients with pleural effusions to determine whether the fluid arose from a transudative or an exudative process. Clinical judgment by an internist before thoracentesis and both serum and pleural fluid protein and lactic dehydrogenase levels (commonly referred to as "Light's criteria") were compared to the patient's final diagnosis. The internist correctly classified 15 of 17 exudative processes and all 16 transudative processes; the presence of any one of Light's three criteria correctly classified 15 of 17 exudative processes, whereas the absence of all three criteria correctly classified 14 of 16 transudative processes. Clinical judgment and Light's criteria are comparable in their ability to predict whether an exudative or transudative process was responsible for the effusion. Both methods are associated with errors, though of different kinds; these errors occurred infrequently. Recognizing the limitations of these methods will permit the most accurate effusion categorization. PMID- 2595417 TI - Abdominoperineal resection for rectal carcinoma: perioperative risk factors. AB - This retrospective review of 37 cases of abdominoperineal resection for adenocarcinoma sought to correlate preoperative clinical characteristics and intraoperative events with the likelihood of subsequent development of specific complications in the postoperative period. Mortality was 3% (1/37), and the complication rate was 76% (28/37), with urologic (49% [18/37]) and pulmonary (30% [11/37]) complications being the most common. Significant perioperative risk factors included a history of cardiac disease, current cardiac medications, diabetes mellitus, an abnormal preoperative electrocardiogram, and extended operation. Factors not associated with an increased risk included age, sex, a history of pulmonary disorders, previous abdominal operations, operative time, and need for transfusions, management of the pelvic peritoneum, or perineal drainage. Such information should reliably identify high-risk patients and therefore should be useful for selecting such patients for palliative or other limited techniques of tumor control. PMID- 2595418 TI - Nosocomial diarrhea: beware the medicinal elixir. AB - An unusual case of osmotic diarrhea that persisted despite fasting led to the discovery of an unexpected source of hospital-acquired diarrhea. Numerous patients were subsequently found to have onset of diarrhea shortly after the initiation of treatment with theophylline elixir. Although theophylline can promote gastrointestinal secretion and motility, this effect should be independent of the route of theophylline administration and the stool should be characteristic of secretory rather than osmotic diarrhea. Patients taking no food orally while taking theophylline elixir continued to have osmotic diarrhea in excess of 1,000 ml/24 hr. Patients whose therapy was switched to intravenous or solid oral theophylline had resolution of diarrhea within 24 hours. The brand of theophylline elixir used was formulated with 30 gm of sorbitol per 240 mg of theophylline; thus a standard regimen of theophylline elixir was delivering four laxative doses of sorbitol daily. A cursory review revealed that many medicinal elixirs are formulated with sorbitol, despite being designated "sugar-free." When patients have osmotic diarrhea in the hospital, beware the medicinal elixir. PMID- 2595420 TI - Comparison of the need for bypass shunt after stroke or transient ischemic attack in 97 patients. AB - Using local anesthesia, we did 97 carotid endarterectomies--48 of them for acute completed stroke, stroke in evolution, or stroke associated with unstable neurologic status, and 49 for transient cerebral ischemic attack. The neurologic status of the awake patients was monitored continuously. Neurologic deterioration resulting from clamping of carotid circulation, and immediate recovery upon release of the clamp indicated need for a bypass shunt. Eighteen of the 48 patients who had had stroke and six of the 49 who had had a transient ischemic attack needed a bypass shunt. The difference was statistically significant (P less than .01). PMID- 2595419 TI - Carcinoid tumors of the gastrointestinal tract: a 44-year experience. AB - We retrospectively studied 112 patients treated for gastrointestinal carcinoid tumors between 1942 and 1986. The three most common sites were jejunum-ileum (27%), rectum (27%), and appendix (21%), followed by colon (12%), duodenum (9%), and stomach (4%). Seventy-five percent of patients had localized disease, primarily in the rectum and appendix. Colon and small bowel tumors were often manifested with metastatic disease. Complete surgical excision of all localized disease was curative in 94% of patients. Corrected five- and ten-year survival rates were 90% and 58%, respectively, in cases of localized disease, whereas in stage III disease, the rates were 46% and less than 30%, respectively. All patients with liver metastasis died within 25 months. A second malignancy, most often adenocarcinoma of the colon, occurred in 25% of patients. Carcinoid syndrome was found in 6% of patients. The best survival rates were noted for appendiceal and rectal carcinoids, and the worst for colon and stomach carcinoids. PMID- 2595421 TI - Imported fire ant as a health hazard. AB - Members of the American Medical Association in 13 southern states were surveyed to assess the magnitude of medical problems caused by stings of the imported fire ant (IFA). Of the 29,205 physicians surveyed, 2,022 (7%) reported treating approximately 20,755 patients annually for reactions to IFA stings. Most patients were treated for local reactions, but 413 (2%) required treatment for life threatening anaphylaxis. PMID- 2595422 TI - Physician advertising: some reasons for caution. AB - Physician advertising is a growing trend which, proponents contend, will bring needed reforms to health care. Among these reforms are better informed patients, reduction in the price of health care, improvement in the quality of care, and reduction in the incidence of malpractice litigation and the cost of malpractice insurance. I argue that physician advertising probably will not accomplish these goals. I also discuss problems with the intent, content, monitoring, and costs of advertising, along with how it may adversely affect the way physicians perceive one another. PMID- 2595423 TI - Context of social awareness: prelude to social service. AB - A required period of social service has recently been suggested as an addition to the medical school curriculum. The intent of this action is to improve the social sensitivity of physicians. If such a requirement is not placed within the appropriate context it may fail to achieve its objectives. Attention to institutional commitment, faculty experience, student selection, and supporting didactic materials are offered as suggestions to improve the utility of a social service requirement. PMID- 2595424 TI - Drugs with anticholinergic side effects. PMID- 2595425 TI - Hairy cell leukemia with an autoimmune syndrome, paraproteinemia, and cryoglobulinemia. AB - We have described an 82-year-old man with HCL who had autoimmune manifestations, paraproteinemia, and cryoglobulinemia. Chemotherapy resulted in a dramatic response, with a decrease in the tumor mass, a reduction in the clinical and serologic features of the autoimmune syndrome, and disappearance of the cryoglobulin, but without a significant change in the serum level of paraprotein. PMID- 2595426 TI - Fatal cardiac arrhythmia in a patient with interstitial myocarditis related to chronic arsenic poisoning. AB - We have reported the case of a 42-year-old man exposed to arsenic at least three times over a ten-month period from an agricultural source. He showed classical symptoms and signs of arsenic poisoning. During chelation therapy and apparent recovery from the poisoning, he suddenly and unexpectedly died; postmortem examination revealed a myocarditis similar to that reported previously. The case demonstrates the need for electrocardiographic monitoring of all patients with arsenic poisoning, during both the initial phase of the illness and convalescence. PMID- 2595427 TI - Intracranial granulocytic sarcoma in postpolycythemia myeloid metaplasia. AB - A 57-year-old man with a ten-year history of polycythemia vera had myeloid metaplasia, extramedullary hematopoiesis, and terminally, possible leukemic transformation with intracranial granulocytic sarcoma. Radiation therapy produced a partial and temporary beneficial response. Intracranial granulocytic sarcoma is typically associated with acute or chronic myelogenous leukemia and has not been previously associated with postpolycythemia myeloid metaplasia. PMID- 2595428 TI - Waterhouse-Friderichsen syndrome caused by Haemophilus influenzae type b in an immunocompetent young adult. AB - A previously healthy 19-year-old woman had a febrile illness with hypotension, progressive cyanosis, and an evolving petechial rash. Despite aggressive therapy in the face of shock and disseminated intravascular coagulation, the patient suffered a cardiac arrest and could not be resuscitated. Haemophilus influenzae type b was cultured from the blood and echovirus 30 from the cerebrospinal fluid post mortem. Fulminant H influenzae type b infection in an immunocompetent adult is rare but should be recognized as a possible cause of the Waterhouse Friderichsen syndrome. PMID- 2595429 TI - Neurogenic hyperthermia in subarachnoid hemorrhage. AB - We have described a patient with neurogenic hyperthermia caused by a diencephalic infarction. His hypothalamic dysfunction was a consequence of cerebral vasospasm from aneurysmal subarachnoid hemorrhage. Persistent elevation of body temperature did not respond to standard therapy, but successful treatment was achieved with cyproheptadine and indomethacin, presumably through antagonism of serotonin and prostaglandin activity. PMID- 2595430 TI - Benign papillary mesothelioma of the peritoneum: a consideration in the differential diagnosis of peritoneal implants. AB - We have reported a case of benign papillary mesothelioma of the peritoneum found incidentally during surgical exploration in a patient with rectal carcinoma. Clinicians and pathologists alike may find it difficult to differentiate this uncommon lesion from metastatic tumors. PMID- 2595431 TI - Metoclopramide-induced parkinsonism. AB - Metoclopramide hydrochloride (Reglan) is a widely prescribed drug for treatment of upper gastrointestinal symptoms. Although the drug is relatively safe, a growing body of literature has noted movement disorders after its administration. We have reported six cases of metoclopramide-induced parkinsonism seen in consultation over a two-year period. Five of these six patients had renal failure. Their parkinsonism improved on discontinuation of metoclopramide therapy. Metoclopramide-induced parkinsonism is not rare, and appropriate dose reduction in patients with renal failure will help reduce the incidence of this morbidity. PMID- 2595432 TI - Lemierre's postanginal septicemia: internal jugular vein thrombosis related to pharyngeal infection. AB - We have described a case of septic thrombophlebitis of the internal jugular vein after an anaerobic pharyngeal infection. This and other septic thrombophlebitides are a part of Lemierre's postanginal septicemia. Early diagnosis and appropriate antimicrobial therapy are important to avoid sequelae. PMID- 2595433 TI - Hypothyroidism: effect on warfarin anticoagulation. AB - Although our observation is not the first case of reduced PT response to oral anticoagulants associated with hypothyroidism, it is the only such interaction reported since 1963, and the first case involving warfarin therapy in a human being. We submit this case as a reminder of a potentially forgotten interaction, and to stress the importance of close monitoring in patients receiving warfarin therapy who have concomitant changes in thyroid function. PMID- 2595435 TI - Mnemonic for treatment of anaphylaxis. PMID- 2595434 TI - "Pseudolupus". PMID- 2595436 TI - Accidental amitriptyline poisoning in a toddler. PMID- 2595438 TI - Tinnitus. PMID- 2595439 TI - [Today's patient]. PMID- 2595437 TI - Caution in upper gastrointestinal X-ray study in constipated parkinsonian patients. PMID- 2595440 TI - [Paid medical services for the population of the USSR]. AB - The state of the network of cost-accounting medical facilities, their role and place in the system of medical paid services for the population are described. The work, economic and fiscal activities of Moscow cost-accounting medical facilities are analyzed. Measures aimed at further improvement of medical facilities providing paid services to the population are proposed. PMID- 2595441 TI - [Standardization of the activities of medical personnel at a department for mental patients with severe somatic pathology]. PMID- 2595442 TI - [Relation of philosophical and medical approaches to the study of life style]. PMID- 2595443 TI - [Methods of component analysis of the dynamics of the incidence of chronic non infectious diseases]. AB - Proceeding from the example of lung cancer the technique of component analysis is provided while studying the dynamics of absolute numbers of newly identified patients and indicators of incidence of chronic noncommunicable diseases. PMID- 2595444 TI - [Various ways of improving the effectiveness of the promotion of a healthy life style]. AB - The analysis of prospects in improving the dissemination of medicohygienic knowledge is provided along with possible criteria for assessing its effectiveness. The principles of differentiation of medico-hygienic education for different age groups of population are formulated. The necessity of continuity of medico-hygienic education is demonstrated along with importance of its adaptation depending on the level of background knowledge, interest in information, attitude to health. PMID- 2595446 TI - [Optimal organization of the activities of polyclinics in the Lvov district]. AB - Day hospitals are successfully functioning at some polyclinics. The treatment in a day hospital shortens the period of temporary disability, enhances the effect of treatment while cutting down its cost. Indications for ambulatory surgical intervention are expanding which sharply decreases the number of purulent complications. The introduction of computers at the departments of periodic medical check-up produced a positive effect. The intensification of labour at polyclinics permits to increase the number of patients served by 43 percent as against envisaged by the plan. PMID- 2595445 TI - [Rehabilitation of patients with myocardial infarction living in rural areas]. AB - The experience gained in the introduction of new organizational structure for providing emergency cardiac care to rural population was summarized and social effectiveness of rehabilitative treatment of 653 rural patients suffering from acute myocardial infarction was studied. Early and centralized hospitalization of patients with myocardial infarction from rural areas to specialized regional, interregional and district cardiological departments, the practical application of the principle of step-by-step treatment made it possible to improve the quality of treatment, to lower the rates of primary qualification for invalidism up to 21.4 percent and provided an opportunity to rehabilitate during 6 months 77.2 percent of patients. Unsolved issues of improving cardiological care to rural population were also discussed. PMID- 2595447 TI - [Training of medical students in economics]. PMID- 2595448 TI - [Increasing the effectiveness of training of medical students in promoting the knowledge of medicine and hygiene]. AB - Fifth-year students of the medical faculty prepare one of the course of lectures on the subject of healthy lifestyle promotion, using methodological literature supplied by the Chair and the necessary information. This work is carried out during hours reserved for independent training under the supervision of teachers. The students deliver these lectures to schoolchildren during days and hours specified by the timetable. The lecturing includes demonstration of visual aids. Independent training and lecturing, on the one hand, promotes positive motivation in students in relation to the most important part of their future activity- dissemination of medical and hygienic knowledge and, on the other, raises the level of hygienic education among schoolchildren. PMID- 2595449 TI - [Maternal mortality in the developing countries of Africa]. PMID- 2595450 TI - [Attitude of rural populations to health]. AB - In the course of standard epidemiological survey conducted in rural medical district attitude to health and willingness of population to participate in the preventive activities is studied. Rural population manifests great interest in popular medical knowledge and health, quite rightly considering it to be the most precious property in life and the overwhelming majority of population express willingness to spend efforts and time to preserve it and give up such bad habits as overeating, use of alcohol, smoking etc. However, the verbal behaviour of rural population does not correspond to their actual mode of life and the latter is not always adequate. The organization of health education is of major importance for the formation of proper behaviour. Health education activities in rural areas have some peculiarities. The role of feldshers in organizing health education is increasing. The establishment of sports and health promoting units in rural areas is also of importance. PMID- 2595451 TI - A fine-structure deletion map of human chromosome 11p: analysis of J1 series hybrids. AB - Deletion analysis offers a powerful alternative to linkage and karyotypic approaches for human chromosome mapping. A panel of deletion hybrids has been derived by mutagenizing J1, a hamster cell line that stably retains chromosome 11 as its only human DNA, and selecting for loss of MIC1, a surface antigen encoded by a gene in band 11p13. A unique, self-consistent map was constructed by analyzing the pattern of marker segregation in 22 derivative cells lines; these carry overlapping deletions of 11p13, but selectively retain a segment near the 11p telomere. The map orders 35 breakpoints and 36 genetic markers, including 3 antigens, 2 isozymes, 12 cloned genes, and 19 anonymous DNA probes. The deletions span the entire short arm, dividing it into more than 20 segments and define a set of reagents that can be used to rapidly locate any newly identified marker on 11p, with greatest resolution in the region surrounding MIC1. The approach we demonstrate can be applied to map any mammalian chromosome. To test the gene order, we examined somatic cell hybrids from five patients, whose reciprocal translocations bisect band 11p13; these include two translocations associated with familial aniridia and two with acute T-cell leukemia. In each patient, the markers segregate in telomeric and centromeric groups as predicted by the deletion map. These data locate the aniridia gene (AN2) and a recurrent T-cell leukemia breakpoint (TCL2) in the marker sequence, on opposite sides of MIC1. To provide additional support, we have characterized the dosage of DNA markers in a patient with Beckwith-Wiedemann syndrome and an 11p15-11pter duplication. Our findings suggest the following gene order: TEL - (HRAS1, MER2, CTSD, TH/INS/IGF2, H19, D11S32) - (RRM1, D11S1, D11S25, D11S26) - D11S12 - (HBBC, D11S30) - D11S20 - (PTH, CALC) - (LDHA, SAA, TRPH, D11S18, D11S21) - D11S31 - D11S17 - HBVS1 - (FSHB, D11S16) - AN2 - MIC1 - TCL2 - delta J - CAT - MIC4 - D11S9 - D11S14 - ACP2 - (D11S33, 14L) - CEN. We have used the deletion map to show the distribution on 11p of two centromeric repetitive elements and the low-order interspersed repeat A36Fc. Finally, we provide evidence for an allelic segregation event in the hamster genome that underlies the stability of chromosome 11 in J1. The deletion map provides a basis to position hereditary disease loci on 11p, to distinguish the pattern of recessive mutations in different forms of cancer and, since many of these genes have been mapped in other mammalian species, to study the evolution of a conserved syntenic group. PMID- 2595452 TI - Cytogenetic analysis of amplification and deamplification of UMP synthase genes in Chinese hamster cells. AB - Chinese hamster lung cells selected for resistance to pyrazofurin and 6 azauridine contain amplified UMP synthase genes. With selection in 5 fluorouracil, cells that have lost the amplified gene copies can be isolated. Reselection of deamplified cells in pyrazofurin and 6-azauridine results in reamplification of the UMP synthase genes. We have used chromosomal banding and in situ hybridization techniques to characterize this cyclic process of amplification and deamplification. Homogeneously staining regions (HSRs) were observed in cells containing amplified copies of the UMP synthase gene but not in cells in which the amplified UMP synthase genes had been lost. After reselection in pyrazofurin and 6-azauridine, abnormally banded regions (ABRs) were observed. Both HSRs and ABRs were located at a single site on the distal regions of a small acrocentric autosome, and both were shown to contain the amplified genes. The majority of 5-fluorouracil-selected cells showed residual marker acrocentric chromosomes of various sizes, suggesting excision of portions of the HSR or ABR as the mechanism of deamplification. The acrocentrics carrying the amplified genes resulted from rearrangements involving chromosome 4, site of the endogenous gene. This reversible selection system provides a unique model for investigating gene amplification and deamplification in association with chromosomal rearrangements and the relationship of G-banding to underlying DNA structure. PMID- 2595454 TI - Molecular cloning of human A1S9 locus: an X-linked gene essential for progression through S phase of the cell cycle. AB - The temperature-sensitive (ts) A1S9 mouse L-cell mutant is defective in an X linked gene essential for the progression of cells through the S phase of the cell duplication cycle. We recently reported the complementation of the ts A1S9 cell defect with total human DNA and the isolation of independent temperature resistant transformants that retained a common set of human specific Alu containing fragments. Here we describe the molecular cloning of these human DNA sequences from one of the secondary transformants. ST-1-0. A genomic library prepared from ST-1-0 was screened with a total human DNA probe, and two recombinant bacteriophages carrying overlapping segments were isolated. The cloned region was extended in both directions using a human X-chromosome specific library. In total, a human region spanning 42 kb in length, and containing all the Alu-specific DNA sequences found in ST-1-0, was isolated in five overlapping recombinant phages. The A1S9 gene appeared to be larger than the DNA recovered in individual phage isolates, as was assessed by transfection experiments. A single copy probe derived from the phage DNA was shown to be conserved in independent primary, secondary, and tertiary transformants of ts A1S9 cells and mapped to the X chromosome by molecular hybridization. Northern blot hybridization of this probe with poly(A)+ mRNA derived from ST-1-0 cells identified a transcript of about 3.6 kb. PMID- 2595453 TI - Spontaneous CHO APRT heterozygotes reflect high-frequency, allele-specific deletion of the chromosome Z4 APRT gene. AB - In Chinese hamster ovary (CHO) cells, heterozygotes for the adenine phosphoribosyltransferase (APRT) locus arise spontaneously at high frequencies. Paradoxically, such heterozygotes yield APRT mutants only at much lower spontaneous rates, suggesting that the high-frequency event may occur at only one of the two APRT genes. In an attempt to understand the genetic basis for the apparent refractivity of one of the APRT alleles to the high-frequency genetic event and to determine whether differences in the genomic environments of the two CHO APRT alleles specifically render one gene more susceptible to high-frequency spontaneous deletion or inactivation, we have mapped the wild-type APRT allele in 16 independently derived spontaneous APRT heterozygotes. In 15 of these 16 heterozygotes, the functional, wild-type APRT gene was found to reside on the Z7 chromosome, indicating that the high-frequency event is indeed highly specific for the Z4 APRT allele. All but one of these heterozygotes were hemizygous for the APRT locus, suggesting that the high-frequency event generally involves deletion rather than spontaneous inactivation or mutation of the Z4 APRT allele. PMID- 2595455 TI - Induction of sister chromatid exchanges by the thymidine analog 5-hydroxymethyl 2'-deoxyuridine. AB - The thymidine analog, 5-hydroxymethyl-2'-deoxyuridine (hmdUrd), was tested for its ability to induce sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells. When tested, hmdUrd was found to be a potent inducer of SCEs in CHO cells under nontoxic conditions. Under these same conditions, hmdUrd was found to be nonmutagenic, as no increase above the background frequency of 6-thioguanine resistant mutants was observed. The induction of SCEs by hmdUrd was suppressed by thymidine. Simultaneous exposure of the cells to low concentrations of hmdUrd and to high concentrations of the free pyrimidine 5-hydroxymethyluracil (hmUrd), which had no effect alone, had a strong synergistic effect on the induction of SCEs. Simultaneous exposure of cells to hmdUrd and to 3-aminobenzamide, a potent inhibitor of poly(ADP-ribose) polymerase, was found to increase the level of SCEs induced by the hmdUrd. These findings support the hypothesis that the formation of hmUra residues in DNA may be an important factor in the genotoxicity of radiation and oxidative damage in mammalian cells. PMID- 2595456 TI - Association of foreign DNA sequence with male sterility and translocation in a line of transgenic mice. AB - We have analyzed a line of transgenic mice derived from injection of a cloned human interferon cDNA. This line manifests total male sterility of males carrying the human sequence, while male littermates not harboring the foreign DNA are fertile. All females are fertile. Karyotypes of transgenic animals show 2:12 translocation. The microinjected sequence maps to one of the translocation chromosomes composed of a large portion of chromosome 12 to which has been translocated a segment of chromosome 2. Analysis of the sterile males reveals significant abnormalities of spermatogenesis and faulty chromosome synapsis that involves the translocation chromosomes. These findings show that transfer of foreign DNA into mouse embryos may lead to chromatin breakage and infertility of transgenic animals. PMID- 2595457 TI - [Hematologic changes in children small for gestational age]. AB - Haematologic and coagulation changes were examined in 60 children whose gestation age was between the 31st and the 39th week and body weight from 950-2650 grams. There were 34 children smaller than they should be for their gestation development, and 26 children whose development correlated with the gestation period. In small children haematologic changes were dominated by polycythaemia with hyperviscosity, thrombocytopenia, reticulosis and leucopenia. The most significant coagulation changes were expressed by prolonged thrombin-time, prothrombin-time and partially thromboplastin-time, decreased fibrinogen with fibrin degradating products, decreased vitamin K factors dependent on coagulation and antithrombin III. In children with normal gestation maturity haematologic and coagulation changes were significantly lower. PMID- 2595458 TI - [Thinking disorders in patients with Parkinson's disease]. AB - Wisconsin Card Sorting Test was carried on patients with Parkinson's disease in order to examine their conceptual thinking. On the basis of the Mini Mental State Examination and Self Rating Depression Scale 30 patients without dementia and depression of different aetiology and clinical picture, were selected. The comparison with the control group revealed a less successful Wisconsin Card Sorting test results in patients with Parkinson's disease, regarding the number of successfully tested categories and the number of perseverations. The behaviour of the patients with Parkinson's disease during the test was discussed from the point of view of prefrontal cortex, i.e. break of frontostriate connections. PMID- 2595459 TI - [Serum myoglobin levels in patients with acute and chronic renal insufficiency]. AB - The serum level of myoglobin was studied in 20 patients with acute renal failure, in 16 chronic renal failure patients and in 94 patients on maintenance haemodialysis. The serum myoglobin level was significantly increased in the oligoanuric phase of acute renal failure, rapidly decreased during diuretic phase and attained apparently normal values in the recovery phase. In patients with chronic renal failure the serum myoglobin level correlated with serum creatinine and creatinine clearance as a measure of the glomerular filtration rate, indicating a major role of kidney in the metabolism of this low-molecular weight protein. It was established that myoglobin could not be removed by dialysis membrane and analysis of the myoglobin level in endstage kidney disease patients on maintenance hemodialysis has shown an important extrarenal catabolism of this protein. PMID- 2595460 TI - [Mortality in carcinoma of the thyroid gland in Yugoslavia]. AB - The article dealing with thyroid gland cancer in Yugoslavia is based on data on the mortality rate over the period from 1971 to 1985. During the observed period the average proportion of thyroid gland cancer was 0.51% (males-0.30%; females 0.81%) in the whole group of malignant tumours in Yugoslavia. In the same period the standardized mortality rate was 0.52 per 100,000 persons, with the following risk difference between sexes: males-0.40; females-0.63 per 100,000 persons. The mortality trend of thyroid gland cancer in Yugoslavia showed a slight increase from 1971 to 1985 (9y = 0.480 + 0.006x). PMID- 2595461 TI - [Acinetobacter calcoaceticus as a cause of infection in wounds and burns]. AB - Over the period from January 1985 to July 1986 2038 samples of the patients with open wounds and burns, treated in the Military Medical Academy in Belgrade, were tested. Acinetobacter calcoaceticus was found in 152 samples (7.45%). The sensitivity to standard hemotherapeutics for Gram-negative bacteria was assessed. Results indicated that Acinetobacter calcoaceticus showed a high resistance to all hemotherapeutics used in this investigation. Even if it was a opportunistic pathogen bacterium its clinical importance was great because in some conditions this bacterium could cause long-lasting and hard infectious treatment. PMID- 2595462 TI - [Serum cholesterol and triglycerides in patients with benign and malignant tumors of the colon and rectum]. AB - There are many epidemiological papers on the relation of lipids especially of cholesterol, and the incidence of colorectal adenoma and cancer. In the studies of pathogenesis of the cancer of the large intestine attention is paid to the role of certain lipoproteins of bile acids and certain gastrointestinal hormones. We examined 30 patients: 10 were healthy subjects (the control group), 9 with colorectal adenoma, 2 with villous adenoma and 9 with adenocarcinoma of the colon and the rectum. The study concerned: total lipids, total cholesterol, total triglycerides, LDL cholesterol, HDL cholesterol, phospholipids, gastrinaemia and insulinaemia. Statistical analysis of the obtained results showed that hypocholesterolemia followed the incidence of adenocarcinoma. This is in accordance with the most frequently quoted literature. The incidence of hypergastrinaemia, however, was found primarily in the patients with villous adenoma, which indicates possible secretory function of the studied tumours. PMID- 2595463 TI - [Staphylococcus and skin diseases--incidence and antibiotic sensitivity]. AB - Bacterial flora of the skin is influenced by several factors (moisture, occlusion, desquamation, microbial antagonism, etc). Changed conditions on diseased skin result in changes of bacterial flora. Bacterial flora was qualitatively determined both in patients with Psoriasis vulgaris, Tinea Pedis, ulcerovarice syndrome, and in the control group. Special attention was paid to Staphylococcus and its sensitivity to antibiotics. The result was as follows: the largest percentage (48%), ob: pathogenic Staphylococcus aureus was found in ulcus cruris then in psoriasis (32%), in enterdigitas areas of legs in patients with mycosis (25%) and in 5% of healthy skin of the control group. High resistance to antibiotics use for a long time (penicillin, ampicillin). and high sensitivity to new antibiotics (Visiren, Abactal), was established. It is concluded that inflamed skin offers good condition for development of Staphylococcus, and that the incidence of this bacteria depends on aetiopathogenesis of the present dermatosis and factors which regulate bacterial flora. PMID- 2595464 TI - [Rapid agglutination tests for the identification of Staphylococcus aureus]. AB - The article deals with rapid agglutination tests for Staphylococcus aureus identification which detect clumping factor and protein A. The tests were compared with standard diagnostic methods: free coagulase, bound coagulase and thermostable deoxyribonuclease, 190 Staphylococcus aureus strains have been examined of which, 105 methicillin susceptible strains, 85 methicillin resistant strains, and 32 coagulase negative staphylococci strains strains. The presence of clumping factor was detected in 100% of examined Staphylococcus aureus strains. No difference between methicillin susceptible strains and methicillin resistant strains was observed. Protein A was present in 96.1% of methicillin susceptible strains and in 90.6% of methicillin resistant Staphylococcus aureus strains. The same test showed false negative results in 12 strains: 4 of which methicillin susceptible and 8 methicillin resistant strains. Coagulase test slide method and protein A detecting test hand one false positive result each for coagulase negative staphylococci examined. The specificity of all tests used was 100% and 99.5% respectively. The authors suggest latex or hemagglutination tests detecting clumping factor and/or protein A for rapid Staphylococcus aureus strains identification in hospital environment. It is important to point out the possibility of getting false negative protein A detecting results in methicillin resistant strains. PMID- 2595465 TI - [Bilateral trans-obturator bypass after graft infection in the aorto-bifemoral position]. AB - The authors describe a patient in whom bilateral transobturatory bypass for revascularization of the lower extremities after infection of the preliminary implanted graft in aorto-bifemoral position, was carried out. The graft was implanted into aorto-bifemoral position after angiographic examination of the patient hospitalized for claudicatory disorders. A year later the patient was hospitalized for infection of the left distal anastomosis manifested by haemorrhage. After re-establishment of haemostasis (ligature of the arteries in the Scarpa's triangle and of the left branch with Y Dacron graft) the infected part was extirpated. Revascularization of the left leg was performed in another surgical act, with transobturatory iliaco-deep-femoral artery (jumping)- popliteal bypass with the use of 8 mm tubular DACRON graft. Three months later infection and haemorrhage appeared in the right inguinal region i.e. on the right distal anastomosis. This time the extirpation of the infected right branch of Y DACRON graft and revascularization of the right leg with right transobturatory aorto-popliteal bypass were performed in one surgical act. Tubular DACRON graft of 8 mm was also used. This case is one of the good examples of appropriate extra anatomic transobturatory bypass in the revascularization of the lower extremities when it is not possible to treat a process in the inguinal region by usual procedures. The curiosity of this case is the bilateral transobturatory bypass. PMID- 2595467 TI - [Drug interactions: mechanisms and clinical significance]. PMID- 2595466 TI - [Mucoregulators: specificity of carbocysteine]. PMID- 2595468 TI - [TSH receptor antibodies determined by the Thybia test in children with hyperthyroidism]. AB - Using a radioreceptor assay Thybia-test, we studied 22 girls with Graves' disease, aged 4.0 to 20.4 years (mean = 13.8 years). Sera of 9 girls were obtained before therapy, 20 during treatment with methimazole, 4 in remission and 2 relapse. The total number of tested sera was 113. Control sera were obtained from 19 age-matched controls. The results of Thybia-test were positive in 7 of 9 girls with Graves' disease before treatment (77.8%) and in both girls in relapse. Of 89 samples of sera taken during drug therapy Thybia-test was positive in 51. Only 3 of 13 sera taken in remission gave positive results. The highest mean values of Thybia-test were detected in patients in relapse (46.2%), and in patients before therapy (23.9%). During treatment mean values became lower (14.4%) and were the lowest in remission of the disease (6.9%). The results of Thybia-test in controls ranged from 0% to 7.5% (mean = 1.93 +/- 2.78%). Significant differences were noticed between mean values of Thybia-test of patients before therapy and controls as well as between patients during therapy and controls. Six girls were studied after discontinuation of thyreosuppressive therapy. In 5 results of Thybia-test were negative. Three of them are still in long remission. Two were in short remission and relaps in both of them was followed by convertion of Thybia-test to positive. At the end of treatment the only patient with positive Thybia-test was in remission and Thybia-test was-later converted to negative. Our study shows that Thybia-test is a valuable method in addition to others used to correlate the natural history of the disease with the results of therapy. We are still unable to make a definite statement on the significance of this method in prediction of relapse and remission of Graves' disease. PMID- 2595469 TI - [The vascular network of the adrenal medulla in experimentally simulated altitude sickness]. AB - Laboratory rats were exposed to the effect of intermittent hypoxia every second day over the 11-day period. Conditions characteristic of 7000 m of height above sea level were imitated. The effect of hypoxia on the adrenal medulla vascular network in rats, sacrificed at different times after the completion of exposure to hypoxic conditions, was investigated. Stereological percentage of the medulla blood vessels was 23% in the control group, 37% in the group with sacrificed rats immediately after the last exposure, and 45% in the group 4 days after the end of experiment. The obtained results showed that increased blood supply in the adrenal medulla was achieved during the experimental treatment. PMID- 2595470 TI - [Complement and immunoglobulin levels in pregnant women with EPH gestosis]. AB - The authors determined C3 and C4 complements, factor B properdin and immunoglobulins G, M and A in 20 healthy pregnant patients and in 20 patients with EPH gestosis. The analysis was performed in mothers sera, umbilical sera and amniotic fluid, and properdin factor B and IgG in urine. They used the nonfellometric technique with immunochemistry analyzer. The C3 complement was very increased in the serum of mothers with EPH gestosis, and complement C4 was slightly increased in the serum of EPH gestosis, and complement C4 was slightly in the serum of EPH gestosis, and complement C4 was slightly increased in the serum of mothers and umbilical sera. Factor B properdin was very increased in mothers sera and decreased in urine. Higher concentrations of immunoglobulin G were found in umbilical sera than in mothers sera. Increased concentrations of sera in mothers, the umbilicus and urine were observed in patients with EPH gestosis. In these patients IgM was decreased in the serum of mothers and the umbilicus. IgM was decreased in the serum of mothers and significantly increased in umbilical sera. Significant changes in patients with EPH gestosis were noted. PMID- 2595471 TI - [Urinary polyamines before and after treatment of malignant tumors]. AB - The concentrations of polyamines (putrescine, spermidine and spermine) were determined in urine of twelve patients with malignant tumors before and after therapy and in twelve healthy patients. The results showed significant increase of urinary concentrations of putrescine, spermidine and spermine in urine of 12 malignant tumour patients. The concentration of urinary putrescine was higher approximately by 6.5 times; of spermidine by 5.8 times and of spermine by 9.8 times in comparison with the results in healthy patients. After the therapy the concentration of urinary putrescine was by 42.3% lower; of spermidine by 34.4% and of spermine by 52.2% lower in comparison with the results obtained before the therapy. The possibility of usage of concentration determination of urinary po therapy efficiency are discussed. PMID- 2595472 TI - [Clinical manifestations of neuroblastoma in children and their effect on prognosis]. AB - There are many prognostic factors in neuroblastoma. In this paper we analyzed the prognostic importance of some clinical factors like age, stage of disease, primary localization and neurological manifestations in children with neuroblastoma. We analyzed 58 children with neuroblastoma who were treated from 1970 to 1988 at the Haematology Department of Children's University Hospital in Belgrade. According to statistical evaluation presence of neurological manifestations and age were not important prognostic factors in children with neuroblastoma. Only primary localization of the tumour and stage of the disease had significant influence on prognosis. PMID- 2595473 TI - [Use of lasers in gynecology]. AB - On the basis of data from literature the authors present the basic principles of laser technique: radiation, specificity of laser knife and biostimulation effects of laser radiation. In connection with the use of laser in gynaecology the authors point out its use since 1971 in the treatment of different acute and chronic gynaecological diseases and in the treatment of sterility. Results of many authors are presented, especially regarding the use of CO2 laser. Some complications that may arise during laser surgery are also presented. Necessary preventive measures for complete staff dealing with laser, are also described. In the authors' opinion laser technique is a significant contribution to the treatment of different gynecological diseases. PMID- 2595474 TI - [Immunologic thrombocytopenic purpura as a clinical manifestation of HIV infection]. AB - Immune thrombocytopenic purpura may be the sole clinical manifestation of HIV infection. Results of the treatment of 6 patients with spontaneous bleeding due to severe thrombocytopenia, are presented. In all patients immune thrombocytopenic purpura was the only clinical manifestation of HIV infection. Four of them were intravenous narcotic addicts, and the other two patients did not belong to high risk groups. Prednisone treatment of 1 mg/kg daily was sufficient to resolve bleeding and achieve platelet count elevation above 50 X 10(9)/l in five of six patients. Lowering the dose of prednisone of therapy withdrawal were associated with a fall in the platelet count. In three patients the complete remission was not achieved and danazol was administered, 600-800 mg orally daily, with variable efficacy. One of these patients achieved platelet count elevation above 50 X 10(9)/l, while the two others did not respond. PMID- 2595475 TI - [Echocardiographic diagnosis of angiosarcoma of the heart]. AB - Cardiac angiosarcoma is the most common primary malignant tumour of the heart that is rarely diagnosed ante mortem. The authors present the case of a 73-year old female with right atrial angiosarcoma that was followed-up echocardiographically for 20 months. Echocardiographic features suggestive of primary and metastatic malignant tumours of the right heart are discussed. PMID- 2595476 TI - [Barium peritonitis caused by perforation of the colon and rectum]. AB - Over the period from 1979 to 1988 the authors treated three patients with perforated colon and rectum, manifested during contrast barium X-ray examination. Perforation of the caecum occurred in one patient; perforation of the sigmoid flexure in the second subject and perforation of the ampulla recti in the third patient. Caecum perforation was spontaneous, and that of the rectum and the sigmoid flexure wall was due to rigid catheter during irigography. The patients were two women and one man. The youngest patient was 50 years old and the oldest was aged 75 years. Surgery of the perforated caecum and ampulla recti was carried out during the first 24 hours, and that of the sigmoid flexure on the seventh day. The following radical operations were performed: the right hemicholoctomy, sigmoid resection with temporary cholostoma, rectum amputation, manyfold drainage of abdominal cavity. Antibodies were also administered. One patient died. PMID- 2595477 TI - [The rigid spine syndrome]. AB - Five patients with the clinical picture of rigid spine syndrome are presented. Three of them were females. All these patients fulfilled the clinical criteria for rigid spine syndrome. On the basis of the analysis of these patients and the data from literature, it was established that Dystrophia musculorum progressiva- Emery-Dreifuse was one of the causes of rigid spine syndrome in one patient. In the other four patients unspecific myopathic changes were found. The only common feature was marked proliferation of endomysium and perimysium (connective tissue). An effort was made to solve the nosological problems on the contemporary level of knowledge. The heterogenous group of rigid spine syndrome was divided into the three subgroups: 1) Rigid spine syndrome with nosologically determined neuromuscular disorder; 2) Rigid spine syndrome on myopathic basis, but nonspecific and unrecognizable as an entity; 3) Rigid spine syndrome with disorders of non-neuromuscular origin, but with that related to bones, joints or connective tissue. PMID- 2595478 TI - [Treatment of status epilepticus with intravenous lidocaine (Xylocaine)]. AB - A case history of a 19-year old epileptic woman with diffuse encephalopathy of unknown aetiology and frequent attacks of status, epilepticus, whose last episode of the status epilepticus was successfully treated with intravenous lidocaine, after several first-line antiepileptic drugs failed to control, it, is presented. Although highly effective in treating refractory status epilepticus this treatment received little attention in clinical practice. We observed no un desired side effects of such treatment. The authors shortly reviewed current knowledge about several widely used treatment protocols. Some specific pharmacokinetic and pharmacodynamic properties of lidocaine during convulsions were also mentioned. A warning was drawn to toxic fide effects of lidocaine which were precipitated by increasing brain-blood pH gradient during convulsions, which in high doses included seizures caused by lidocaine per se. The effects of high dose lidocaine on the latencies and the amplitudes of the BAER and possible ways for mechanism of drug action were also reviewed. PMID- 2595479 TI - [The clinical significance of immunoglobulin A in pediatric pulmonology]. PMID- 2595480 TI - [Catheter-induced atrial thrombi following central contrast medium injection in venous DSA]. PMID- 2595481 TI - [An intraspinal perineural cyst]. PMID- 2595482 TI - [Reorganization of the documentation of findings of imaging study technics]. PMID- 2595483 TI - [Adjustment of the film tension and the film-screen combination in the detection of low contrast in x-ray diagnosis. I. Theory and method of measurement]. PMID- 2595485 TI - A multi-allergen screening test for suspected allergic disease in coloured children. AB - The measurement of total serum IgE levels is widely used as a screening test for allergic disease but lacks specificity in South African subjects because of the presence of ethnic and environmental factors, e.g. parasite infestation, which also raise total serum IgE. The reliability of a new in vitro multi-allergen test, Phadiatop (Pharmacia), which is not influenced by parasitic infestation, was investigated as a screen for allergic disease in coloured children. Phadiatop assays and total serum IgE levels performed on 18 children with known allergic disease were compared with 21 non-allergic individuals. All the allergic, but only 2 of the non-allergic children had a positive Phadiatop result (P = less than 0.01; chi-square test) but there was no significant difference between the number of allergic or non-allergic children with elevated total serum IgE levels (P = greater than 0.1). The Phadiatop test demonstrated a specificity of 90% compared with 28% for total serum IgE. The predictive value of a negative Phadiatop result was 90% compared with 54% for total serum IgE levels. These data indicate that the Phadiatop test is a more specific screening test for allergic disease than total serum IgE levels in coloured children. PMID- 2595484 TI - Initial hormonal and metabolic profile in critically ill patients with community acquired lobar pneumonia. AB - A prospective study of 18 critically ill patients with community-acquired lobar pneumonia was undertaken at Hillbrow Hospital, Johannesburg, in order to document the initial plasma hormonal and substrate profile as part of the stress response to the infection. The results of these studies, carried out before therapy, were compared with the results in a group of healthy fasting adults. Highly significant (P less than or equal to 0.005) increases in the mean plasma levels of adrenaline, noradrenaline, human growth hormone, cortisol, glucose and free fatty acids were noted in the study group, with a lesser increase in the prolactin concentration (P less than or equal to 0.01). The levels of dopamine, glucagon, insulin and adrenocorticotrophin did not show any significant change. No significant differences were found in the hormonal profile when comparing survivors with non-survivors. The neuro-endocrine hormonal and metabolic responses in pneumonia appear to be similar to those seen in other stress situations and failure of the initial stress response does not appear to contribute to the mortality of critically ill patients with community-acquired lobar pneumonia. PMID- 2595486 TI - Colorectal cancer in young blacks. An epidemic in Gazankulu? AB - Eight cases of colorectal cancer at Elim and Malamulele Hospitals, Gazankulu, occurring in a 7-month period in young black people, are presented. Epidemiological and aetiological considerations are discussed. PMID- 2595487 TI - Improvement in left ventricular ejection fraction after surgery for mitral stenosis. AB - It is recognised that patients with mitral stenosis may have impaired left ventricular function. The reasons for this are speculative and the effects of surgical relief of stenosis on left ventricular function unknown. Five patients showed dramatic improvement in left ventricular ejection fraction after surgery. Possible reasons include altered loading conditions, changes in ventricular interaction and partial restoration of the normal anatomical structure of the mitral valve complex. PMID- 2595488 TI - [The incidence of ischemic heart disease in white South Africans cremated in Pretoria, 1978-1985]. AB - The prevalence of ischaemic heart disease was studied in a population selected on the basis of an application for cremation by the next of kin. In the age group 35 44 years 15.2% of the deaths were ascribed to ischaemic heart disease (IHD), while the corresponding figure in the general population was 27.2%. In females in the age group 45-54 years IHD was responsible for 9.3% of the deaths; the corresponding prevalence in the general population was 18.3%. The figures for all age groups and both sexes were 22% for the cremation group and 24.5% for the general population. In the economically active group (20-65) years, the figures were 20.0% for the cremation group and 30% for the general population. There was no significant difference in the IHD deaths between Afrikaans-speakers and other language groups. These findings are not necessarily applicable to the general population, as the cremation group is not truly representative, but the consistently lower prevalence of IHD suggests that there is over-reporting of this disease in unmonitored death certification. PMID- 2595489 TI - Human pregnancy after transfer of intact frozen-thawed embryos. AB - Since the birth of the first baby as a result of in vitro fertilisation (IVF) in 1978, many clinics around the world have achieved pregnancies and births for their patients by using IVF and gamete intrafallopian transfer procedures. With the storage of excess embryos, multiple laparoscopies can be avoided; this has favoured the development of better cryopreservation techniques. In our clinic 8 cell human embryos are frozen in a 1.5M dimethyl sulphoxide solution as cryoprotectant using the slow freeze-thaw method. Sixteen thawed embryos were replaced in 8 patients, resulting in 1 pregnancy. Of the thawed embryos 51.6% survived the freezing process in that they had 50% or more of the original number of blastomeres and also the zona pellucida intact. PMID- 2595490 TI - Cervical cytological services in the Orange Free State. Demographic characteristics. AB - In the Bloemfontein academic hospitals the incidence of infiltrating cervical cancer is four times that of severe cervical intra-epithelial neoplasia (CIN III). A cross-sectional survey was therefore conducted to identify the extent of cervical cytological services in the Orange Free State. From the four major laboratories dealing with the population of the OFS all cytological reports of one randomly chosen working day per month in 1985 were analysed for three demographic variables: age, race, and locality according to census district. As a control, similar demographic variables were identified from national census figures for 1980, limited to females aged 15-65 years. The follow-up of patients with CIN III diagnosed cytologically in the academic hospitals in Bloemfontein was determined. Results showed significant differences (P less than 0.001) in age, race and locality between the census population and that submitted to cytological screening. Acceptable figures were virtually limited to Bloemfontein, predominantly in white patients, while three-quarters of the population of the OFS is black. The peak frequency in the age distribution in the screened population was 25-35 years and 15-24 years for the census population. Follow-up for patients with CIN III was 65.5%. The conclusion is that the female population of the OFS is not representatively reached by existing cytological services. PMID- 2595491 TI - Inter-observer variation in symphysis-fundus measurements. A plea for individualised antenatal care. AB - Two groups of midwives were compared with regard to ability to detect small-for gestational-age (SGA) babies using symphysis-fundus (S-F) measurements. The patients were all low-risk obstetric patients. In group A 2 midwives provided antenatal care to 97 patients; 14 delivered SGA babies, of which 12 were identified by S-F measurements (sensitivity 85.7%). In group B 15 midwives provided antenatal care to 126 patients, 12 delivered SGA babies, and 5 of these were identified (sensitivity 41.2%). It is considered that this difference was due to inter-observer variability. A plea is made for individualised antenatal care. PMID- 2595492 TI - Statistical significance versus clinical relevance. Part II. The use and interpretation of confidence intervals. AB - Most clinical studies are carried out to estimate some quantity, such as a difference in means or proportions. However, significance testing without controlling the power of the test is not an appropriate tool for this purpose, since practical conclusions are difficult (or even impossible) to formulate. The use of confidence intervals, which provide effective information in this regard, is recommended and illustrated by means of an example. With confidence intervals, it can clearly be stated in what range the population value (difference, proportion, or any other point estimate) is likely to lie. A clinically relevant interpretation can then be made without difficulty. PMID- 2595493 TI - Auto-erythrocyte sensitisation--the Gardner-Diamond syndrome. A case report. AB - A 34-year-old woman with a 3-year history of easy bruising of unexplained aetiology in anatomical sites consistent with self-infliction is described. Despite major surgery, the patient had never experienced inappropriate bleeding. Owing to psychological instability, the possibility of auto-erythrocyte sensitisation was considered; this was confirmed by subcutaneous injection of autologous red cells and haemolysate, which caused local tenderness and induration. This manifestation of Gardner-Diamond syndrome is unusual and is reported to draw attention to its existence and perhaps thereby avoid unnecessary and costly investigations. PMID- 2595494 TI - Drowning this summer. PMID- 2595495 TI - Whooping cough--a neglected disease in southern Africa. PMID- 2595496 TI - Screening for diabetes in pregnancy. PMID- 2595497 TI - Effects of cannabis smoked together with a substance sold as Mandrax. PMID- 2595498 TI - New combined HIV-1 and HIV-2 test. PMID- 2595499 TI - The Tuberculosis Control Programme--a time to re-evaluate? PMID- 2595500 TI - Blood pressure and blood glucose--is there a link? PMID- 2595501 TI - Sewage to sea--what are the implications? PMID- 2595502 TI - The regulation of medicines in South Africa--does it control costs? PMID- 2595503 TI - Immunophenotyping in the diagnosis and classification of acute leukaemia. AB - Ninety-four consecutive patients with acute leukaemia were analysed using cytochemical stains and, in selected individuals, a panel of monoclonal antibodies combined with measurement of the enzyme terminal deoxynucleotidyl transferase. These results were correlated with the French-American-British morphological classification. Acute non-lymphoblastic leukaemia was diagnosed in 55 individuals on the basis of morphology and cytochemical criteria; 6 of this group were further studied with antibodies directed against specific myelomonocytic antigens, but no further clinically useful information was obtained. Blasts from 36 patients did not stain with either Sudan black or myeloperoxidase. These individuals were considered to have acute lymphoblastic leukaemia (ALL) and were further assessed with monoclonal antibodies directed against epitopes expressed on cells of lymphoid lineage; 10 were classified as arising from T precursors; 23 were of B lineage, of which 13 marked as common, 6 as null, 1 as pre-B, 2 as B-ALL and 1 to have a pattern characteristic of lymphoblastic lymphoma. Two cases could not be classified and 1 was found to have megakaryoblastic features. In a further 3 patients who had undergone lymphoblastic transformation as a terminal event in the course of chronic granulocytic leukaemia, 2 were immunophenotypically common and 1 was marked as a null cell. This study confirms the value of monoclonal antibodies for accurately assigning lineage to the acute leukaemias and particularly in those situations where conventional morphological criteria and cytochemical markers are inconclusive. PMID- 2595505 TI - Involvement of the appendix in ovarian epithelial cancer--an update. AB - Appendicectomy was performed at the time of primary definitive surgery in 60 of 102 patients with epithelial ovarian cancer at Johannesburg Hospital over a 9 year period (January 1979-December 1987). Metastases were present in 37 of the 46 (80.4%) appendices removed from patients with advanced disease (stage III or IV) and in only 1 of the 14 patients (7.1%) with early disease. Metastases were not limited to serosal implants and included vascular and lymphatic space involvement, chronic obliterative appendicitis and almost complete replacement of the appendix by adenocarcinoma. The role of appendicectomy in the surgical management of epithelial ovarian cancer is discussed. PMID- 2595504 TI - Multiple primary thyroid and breast cancer in Israel, 1960-1976. AB - The occurrence of breast and thyroid multiple primary neoplasms has been evaluated using data from the Israel Cancer Registry. During the 16 years 1960 1976, 3,072 cases of thyroid cancer were registered in Israel. The occurrence of a second primary tumour was reported in 92 of these patients. In this latter group were 25 female patients (27%) with breast cancer, developing synchronously in 7 cases and metachronously in the remaining 18. The average age at the time of appearance of breast cancer was 50 years. Most of the patients (84%) were of European origin. The most common histological types were ductal and intraductal carcinoma and scirrhous adenocarcinoma. The possible aetiological factors common to breast and thyroid cancer are discussed. Efforts aimed at improving the survival of patients with thyroid cancer must incorporate strategies for the early detection and treatment of secondary breast cancer. PMID- 2595506 TI - Tumour marker CA125 levels in a variety of benign and malignant conditions. AB - The levels of tumour marker CA125 were established in 515 patients with a variety of benign and malignant conditions. With a specificity of 60.3% and an overall sensitivity for malignant tumours of 54% (extra-ovarian serous papillary carcinomas 100%), it is the most reliable tumour marker at present available for epithelial ovarian cancer and is of considerable value in the management of this condition when considered in conjunction with other clinical measurements. PMID- 2595507 TI - Life after death--mortality statistics and the public health. AB - The process by which mortality statistics are compiled in the RSA and the potential impact on public health are discussed. The use of the international death certificate is outlined; this is compared with the South African death certificate to illustrate the importance of establishing the chain of events leading to death. The distinction between underlying and direct causes of death in compiling mortality statistics and planning public health intervention is considered. The major part played by medical practitioners in the death certification process is emphasised, and some of the areas in which mortality data could be improved are highlighted. PMID- 2595509 TI - An unusual cause of dyspepsia. PMID- 2595508 TI - The Tuberculosis Control Programme, 1985-1986. Results of the data-capturing programme instituted by the Department of National Health and Population Development and the Standing Committee on Epidemiology of the Regional Health Organisation for southern Africa. AB - The Tuberculosis Control Programme during 1985 and 1986 in the seven health regions of the RSA is described. This information has not previously been available. In 1986 the total tuberculosis case load exceeded 90,000. Of about 56,000 patients in whom the outcome was known, nearly 44,000 were discharged from the programme cured, about 9,500 absconded from therapy and 3,000 died. About 222,000 suspects or contacts of cases were investigated. Analysis of the data by health region revealed regional differences of prevalence rates, predominance of inpatient or outpatient treatment, cure rates, the ratio of new tuberculosis suspects or contacts found for every new confirmed case, and the cost of the programme per case and per capita of the population. Although these data must be interpreted cautiously, it is hoped that they will be valuable to all health workers fighting this major infectious disease in South Africa. PMID- 2595510 TI - Blood transfusion and HTLV-I-associated myelopathy. PMID- 2595511 TI - Vancomycin-induced neutropenia. PMID- 2595512 TI - [A case of chromosome-13-abnormality]. PMID- 2595513 TI - Gonorrhea prevalence in the Maryland state prisons. AB - During a 6-month period from July 1 through December 31, 1986, 2,598 consecutive men were screened for gonorrhea upon entry into the Maryland Division of Corrections. Twenty-eight men (1.1%) demonstrated positive cultures for gonorrhea with 27 of them (92%) asymptomatic. This prevalence is substantially lower than other rates reported from prisons and detention centers. Although the role of asymptomatic males as a reservoir for gonorrhea has been well delineated, standard recommendations for screening high-risk male populations such as prison inmates have not been established. These data suggest that screening in some correctional facilities may not be cost-effective given the low prevalence observed. In addition, contact tracing may be delayed by long holding periods in local detention facilities prior to transfer to the state prison system. These data underscore the need for additional analysis to determine the most effective program structure for screening in correctional facilities and detention centers. PMID- 2595514 TI - The multiple dimensions of sexual behavior as risk factor for sexually transmitted disease: the sexually experienced are not necessarily sexually active. AB - Sexual behavior is a crucial risk factor for sexually transmitted diseases (STDs), but no national data exist to define a true population at risk. Instead, limited information describes sexual behavior in specific population groups (adolescents, women in their twenties) only in terms of a single dimension: sexual experience. To address the multiple dimensions of sexual behavior, we analyzed data collected from a nationally representative sample of reproductive age women in the 1982 National Survey of Family Growth (NSFG). We found 86% of women aged 15-44 to be sexually experienced. Teenagers are the least experienced (45% and 56% of whites and others, respectively) and the least sexually active of all reproductive women. While sexual experience increases with age, sexual activity shows a curvilinear age pattern: it increases up to age 35 and decreases slightly from age 35 to 44. Teenagers report the least consistent sexual activity (less than 25%) and the highest level of abstention (38% and 31% for whites and others, respectively) following sexual experience. These findings indicate sexual experience as a measure of sexual behavior should be further refined to provide a more accurate estimate of the population at risk for STD. PMID- 2595515 TI - Assessing behavioral risk for HIV infection in family-planning and STD clinics: similarities and differences. AB - Four hundred fifty-five women in family-planning and sexually transmitted disease (STD) clinics were surveyed to determine the degree of participation in behaviors known to be associated with increased risk of human immunodeficiency virus (HIV) infection. A previous history of STD (20%) and multiple sexual partners (73%) were shown to be the high-risk behaviors most prevalent in these populations. Sexual intercourse with persons in high-risk groups (6%) and intravenous (IV) drug use (3.7%) were less prevalent. Differences between the populations from each type of clinic and between races were noted. Overall, almost one third of family-planning clinic clients and nearly half of STD clinic clients reported participation in at least one risk behavior, emphasizing the need for educational efforts toward disease prevention in these settings. PMID- 2595516 TI - Human immunodeficiency virus (HIV) seroprevalence in persons attending STD clinics in the United States, 1985-1987. AB - We reviewed published and unpublished studies on seroprevalence of HIV antibody in persons attending sexually transmitted disease (STD) clinics in the United States from 1985 through 1987. We identified 23 studies from 16 states; nine studies determined risk factors for HIV. Overall, 899 (4.2%) of the 21,352 clinic attendees were seropositive; the seroprevalence rate was higher for men (5.9%) than for women (1.7%). Clinic seroprevalence ranged from 0.5% to 15.2% (median, 3.5%), reflecting in part the proportion of all attendees who were homosexual or bisexual, intravenous-drug users (IVDUs), or heterosexual partners of bisexual men or IVDUs (median proportion, 21.8% for the nine sites with this information). Most HIV-seropositive persons were at recognized risk (median for the same nine studies, 85.3%). Homosexual/bisexual men had the highest seroprevalence (median, 32.2%), followed by heterosexual IVDUs (median, 3.6%). Heterosexuals who denied intravenous-drug use had a median rate of 0.9%, which strongly correlated with rates in IVDUs in the same clinics (r = 0.88). We conclude many STD clinic attendees are infected with HIV. Because AIDS is an STD and seroprevalence has been associated with other STDs, STD clinics are important sites for HIV surveillance and risk-reduction education. PMID- 2595517 TI - Clindamycin and ibuprofen effects on chlamydial salpingitis in mice. AB - To evaluate the effects of clindamycin and ibuprofen on a model of upper genital tract chlamydial infection in mice, 64 Swiss Webster white mice were inoculated in the left ovarian bursa with a mouse pneumonitis strain of Chlamydia trachomatis. Chlamydia-inoculated mice received clindamycin, ibuprofen, clindamycin and ibuprofen, or no treatment. Mice were killed at intervals, and their genital tracts were examined grossly and microscopically for evidence of infection and cultured for Chlamydia. Sixty-seven per cent of inoculated, untreated mice manifested gross evidence of inflammation compared with 22.4% of mice in any treatment group (P less than .025). C. trachomatis was isolated in 10.2% of mice treated with any drug regimen, whereas 46.7% of untreated mice were culture-positive (P less than .025). In this model, therapy with clindamycin, ibuprofen, or both drugs in combination decreased gross and histologic evidence of inflammation as well as the rate of recovery of C. trachomatis from the genital tract. PMID- 2595519 TI - Surgical endoscopy. PMID- 2595518 TI - The effects of an STD educational intervention on follow-up appointment keeping and medication-taking compliance. AB - A sexually transmitted disease (STD) educational intervention was examined to determine whether or not it influenced patient compliance with follow-up appointment keeping and with medication taking. Also measured was whether compliance varied due to the type of counselor utilized (clinician or nonmedical interviewer). A sample of 340 men attending a Memphis, Tennessee, STD clinic were divided equally into experimental and control groups. The experimental group was exposed to a structured educational intervention. The control group received standard information according to the clinic protocol. Of the 340 subjects entered into the study, 224 (66%) returned for a follow-up. Of those returning, 121/170 (71%) were in the experimental group (P = .05). Mean scores for compliance with medication taking were not statistically significant. The type of counselor utilized did not affect the level of compliance with either dependent variable. PMID- 2595520 TI - The surgeon as endoscopist. AB - Because extraordinary benefits accrue to the patient when the surgeon can view the site of disease first-hand, the gastrointestinal surgeon must be a proficient endoscopist, and endoscopy must be part of gastrointestinal surgery. Leaders of surgical organizations and surgeon educators, upon whom rests the responsibility for shaping policy and educating medical students and residents, should remain alert to the need to maintain a substantial surgical presence in gastrointestinal endoscopy. PMID- 2595521 TI - Establishing an endoscopy unit for surgical training. AB - Gastrointestinal endoscopy is slowly returning to the core of surgical resident training. The intent is to integrate endoscopy into the mainstream of surgical education such that it will be approached and used the same as any of the many diagnostic and therapeutic tools at the surgeon's disposal. The current feeling is that although endoscopy should be intimately incorporated into training, there is a level of technical expertise required such that a dedicated teaching experience must be provided. This education must be directed by a surgeon experienced in endoscopy; we should not abdicate this responsibility to others. The training program should be founded on education, clinical practice, and research, with technical skills to begin in PGY 2 or PGY 3 and be incorporated throughout the remainder of training. Quality assurance should be monitored closely but not separately from that of the surgical service. Certification of the resident should not depend on numbers, nor be specifically singled out from the body of surgery. There is adequate patient demand to establish the endoscopy unit under the supervision of a surgeon, either as a separate unit or as part of the surgical clinic. However, as the number of endoscopic procedures performed approaches 600 per year, a fully dedicated endoscopy room and full-time gastrointestinal assistant technician are required. The most efficient method of postsedation recovery is through coordination with an ambulatory surgery unit or postoperative recovery room. The current standard for equipment is video endoscopy in order to provide the most efficient method for surgical training. PMID- 2595522 TI - Endoscopic retrograde cholangiopancreatography, endoscopic sphincterotomy, and biliary drainage. AB - Endoscopic retrograde cholangiopancreatography, endoscopic sphincterotomy, and endoscopic biliary drainage have dramatically changed the diagnosis and management of disorders of the pancreas and hepatobiliary tract. Endoscopic retrograde cholangiopancreatography will provide a high-resolution study that will define accurately the nature and location of the disease process involving the pancreas or bile ducts. Although sonography, CT, and, recently, MRI may provide clues to the diagnosis, it often remains for endoscopic retrograde cholangiopancreatography to establish the diagnosis with certainty. Endoscopic sphincterotomy has been invaluable in the management of common bile-duct stones. In patients who have had their gallbladders removed, sphincterotomy has avoided reoperation in the same field and the risk of general anesthesia. Sphincterotomy also is assuming an increasingly important role in the management of common-duct stones in patients with their gallbladders in situ who are poor operative candidates. In these patients, sphincterotomy likewise avoids the risk of general anesthesia and the surgical stress of opening a major body cavity. The technique has also proved to be helpful in the palliative treatment of ampullary and distal common bile-duct carcinomas in those patients who are poor operative candidates. Finally, sphincterotomy has found a role in the treatment of choledochal cysts and may provide relief of pain in those patients with the elusive diagnoses of postcholecystectomy syndromes, biliary dyskinesias, and sphincter of Oddi dysfunction. Endoscopic biliary drainage is becoming an increasingly popular option for the palliation of malignant biliary obstruction. In those patients who are poor operative candidates, the risk of general anesthesia and major surgery is avoided. In those patients with obviously incurable tumors, endoscopic drainage allows for a brief hospitalization without surgery in the face of a short life expectancy. PMID- 2595523 TI - Intraoperative and postoperative biliary endoscopy (choledochoscopy). AB - Surgical exploration of the common bile duct is performed blindly, and perhaps this is one of the reasons the incidence of retained stones is higher than it should be. The introduction of the choledochoscope was promising, but a recent survey found that although a majority of hospitals where biliary surgery is performed have the instrument in the operating room, only a small percentage of surgeons use it routinely. This means that the general surgeon is not an endoscopist and choledocholithotomy cases are only 10 to 20 per cent of the existing biliary material. The introduction of the video choledochoscope shortened the learning curve for the surgeon significantly. The enlarged image can be seen conveniently from a distance with both eyes. Intraoperative stone retrieval requires four hands, and with video endoscopy, movements are coordinated, as the entire operating team can see the process. Therefore, the procedure is more precise and faster. The few missed stones can be removed with ease in the postoperative period through the T-tube tract. The procedure is safe and accurate and can be performed on an outpatient basis. PMID- 2595524 TI - Colonoscopic management of polypoid lesions. AB - Virtually all colonic polyps may be removed endoscopically and with great safety provided the endoscopist is experienced with diagnostic colonoscopy as well as electrosurgical principles and hazards. Many polypoid protrusions will not require total removal or even sampling. Those lesions thought to need formal surgical management will require not only adequate tissue sampling but also accurate localization for the surgeon. PMID- 2595526 TI - Intraoperative radiation therapy. Second international symposium. September 11 14, 1988, Innsbruck, Austria. Abstracts. PMID- 2595525 TI - Colonoscopic diagnosis and treatment of lower gastrointestinal bleeding. AB - Methods of diagnosis and treatment of lower gastrointestinal bleeding depend on the rate of bleeding and the amount of blood lost. If bleeding is occult, colonoscopy is the single best way to determine the source, if bleeding is gross but mild, causing melena or small amounts of hematochezia, colonoscopy or a combination of flexible sigmoidoscopy and double-contrast barium enema should be used to evaluate the colon. In most patients with melena, the upper tract must be examined endoscopically. Acute lower gastrointestinal bleeding stops spontaneously in 75 to 90 per cent of patients, permitting preparation of the colon before colonoscopy. If bleeding is continuing, diagnostic options include colonoscopy with no preparation of the colon, relying on the cathartic effect of blood, or a red cell radionuclide scan followed by angiography if the scan is positive. A bleeding lesion seen on angiography is usually treated by infusion of vasopressin. Colonoscopic treatment of a bleeding site uses the BICAP probe, heater probe, or argon laser. Patients who bleed severely and those who do not respond to treatment or rebleed after treatment are candidates for operation. Segmental resection is preferred if the bleeding site is known. If not, total colectomy with ileorectal anastomosis may be necessary. A mortality rate of 10 to 15 per cent in patients with severe bleeding reflects the advanced age of many of these patients and the difficulty of managing gastrointestinal bleeding in the presence of associated medical conditions. PMID- 2595527 TI - [Coping with disease and management of therapy in patients with cancer with special reference to radiotherapy. An overview]. AB - The actual state of research is reviewed, focussing on the psychosocial aspects of cancer. The argumentation is oriented at distinguishable stages during the course of disease. Further topics are doctor-patient-relationship, compliance, coping and the evaluation of psychosocial care. PMID- 2595528 TI - [A new multi-channel LDR/MDR-afterloading-system (Inter-Pal-C38)]. AB - The methods of temporary interstitial implantation of iridium-192 seed chains have been applied in Erlangen for two years in many cases of squamous cell carcinoma in the head and neck area, the cervix uteri or the anal duct. The afterloading procedure which at the beginning had to be performed manually involved partially considerable radiation-exposures of medical and nursing staff. Therefore we have developed a 38-canal machine for remote control afterloading with iridium-192 seed chains in LDR and MDR therapy which is working in a similar way as the already established methods of remote control afterloading in HDR therapy. Special technical features are the automatic afterloading procedure, the disconnecting of patient and machine for any length of time, the possibility to use the machine for several succeeding patients, and the modern computer control by an IBM PC with color monitor and alpha-numerical keyboard. The new machine is fast and easy to handle, protects the staff completely against radiation and, due to the possibility of disconnection and free mobility, makes it easier and more comfortable for the patient to stay within the radioprotection room. PMID- 2595529 TI - [Uncertainties in the localization of radiation sources in brachytherapy]. AB - While investigating ways to solve the problem of locating radiation sources applied in brachytherapy a device was constructed which enables a precise assessment of their or their applicators' position from two only roughly positioned orthogonal radiographs. The overall accuracy (including exposure and evaluation) achieved is +/- 1 mm. The constructional elements and the evaluation algorithm are described and the influence of the location uncertainty on the uncertainty of the dose applied are discussed. PMID- 2595530 TI - The correlation between cell survival curve and dose response curve of micronucleus (MN) frequency. AB - The correlation between cell survival curve and dose response curve of MN frequency following irradiations was studied using cytokinesis-block method. Both dose response curves were analyzed by linear quadratic model, i.e. SF = exp ( alpha D-beta D2) and MN frequency = aD + bD2 + C. A good correlation between alpha/beta and a/b ratios was observed in repeated paired experiments (= 0.97). When the cells were treated with BUdR, alpha-type radiosensitizer, a value in dose response curve of MN frequency increased but b value did not. These data present that MN frequency assay using cytokinesis-block method is available as a tool of rapid assay of radiosensitivity of cells. PMID- 2595531 TI - Patterns of alveolar bone loss in the assessment of periodontal treatment priorities. AB - The main objective of this series of investigations was to develop a model to assess periodontal treatment priorities based on the amount of remaining alveolar bone support. To obtain proper data to generate this model, a cross-sectional and a longitudinal investigation of periodontal disease were undertaken. On radiographs from 531 subjects aged 25-75 years, assessments of alveolar bone level (ABL), i.e. the distance between the cementoenamel junction and the most coronal level of the alveolar bone support, were performed at the approximal surfaces of all present teeth A small proportion of the sample (11%) showed advanced alveolar bone loss (mean ABL greater than or equal to 6 mm). An ABL of greater than or equal to 6 mm was found in 13% of the tooth sites examined. The severity of alveolar bone loss was more pronounced in the maxilla than in the mandible. Incisors showed the highest and molars the lowest frequency of advanced alveolar bone loss. The assessments of ABL were repeated on radiographs taken 10 years later from 194 of the subjects. An average longitudinal tooth loss of 3.8 teeth/subject was noted. Differences in alveolar bone height were calculated. It was observed that 7% of the subjects and 10% of the tooth sites had experienced advanced additional loss of alveolar bone. The mean annual alveolar bone loss varied between 0.07-0.14 mm in ages between 25 and 65 years. 70 year old subjects showed the most pronounced rate of additional bone loss (0.28 mm/year). A subsequent clinical examination revealed an overall high degree of agreement between the radiographic and the probing attachment level determinations. In 92% of the tooth sites with measurable ABL and probing attachment loss the difference between the two assessments was within 2 mm. However, the agreement became poorer with increasing severity of periodontal tissue breakdown. The data on the longitudinal alveolar bone level changes generated age- and tooth type specific "critical" bone loss limits. These described amounts of bone loss beyond which therapeutic intervention must be performed in order to secure proper function of the teeth throughout life. A random sample of 192 industrial employees was examined radiographically and clinically. When traditional criteria were employed to assess the periodontal treatment needs, 100% of the subjects and 70% of the approximal tooth sites examined required therapy. Bleeding on probing together with the described alveolar bone loss limits identified the 40% of the subjects and the 2.5% of the tooth sites which should be given priority with respect to periodontal therapy. PMID- 2595532 TI - [Proposal for a new principle program: a political change in course]. PMID- 2595533 TI - [Take feelings of guilt seriously!]. PMID- 2595534 TI - [Ethical problems. Duty to secrecy]. PMID- 2595535 TI - [Norwegian Nurses' Association project: quality assurance and development of standards in nursing services]. PMID- 2595536 TI - [Patient classification and standards in nursing quality (I). A documentation model for the need of personnel resources and for improved quality in nursing care]. PMID- 2595537 TI - [Care for the aged. How can we set priorities in community resources? An analysis of variations in activities and resource utilization]. PMID- 2595538 TI - [Initiative, positive attitude and the will to cooperate]. PMID- 2595539 TI - [Food and nutrition activities in home-based care for the aged]. PMID- 2595540 TI - [Cytostatics as infusion therapy at home]. PMID- 2595542 TI - [Executive Board. Council for Nursing Ethics under discussion]. PMID- 2595541 TI - [General practice--disregarded as primary care activity]. PMID- 2595543 TI - [A common attitude]. PMID- 2595544 TI - [Low self-esteem is a terrible burden for nursing]. PMID- 2595545 TI - [Export hospital is open for Danish citizens]. PMID- 2595546 TI - [Stress in nursing. Interview by Peter Vestergaard]. PMID- 2595547 TI - [Children's health. Children's group provide security and self-confidence]. PMID- 2595548 TI - [Salaries and employment. Endorsement of a historical security agreement]. PMID- 2595549 TI - [Open question to the Perspectives' Committee]. PMID- 2595550 TI - [A better introduction stems the exodus from psychiatric departments]. PMID- 2595551 TI - [Island nurses live in a world of their own]. PMID- 2595552 TI - [Secret AIDS testing]. PMID- 2595553 TI - [Prehospital treatment. Proposal for acute helicopter preparedness for the Storebaelt platforms. Interview by Lars Peter Bergqvist]. PMID- 2595554 TI - [Health visiting. Sickness and health in Danish and Turkish. Interview by Grethe Kjaergaard]. PMID- 2595555 TI - [Health visiting. Children's needs are culturally determined]. PMID- 2595556 TI - [Cross-professional team work. Mr. NN challenges nursing personnel]. PMID- 2595557 TI - [New education in the melting-pot at the College]. PMID- 2595558 TI - [Open letter. Reduced quality for consumers of health care]. PMID- 2595560 TI - [The orthodox leader]. PMID- 2595559 TI - [Education. Peer supervision as a tool for growth and development]. PMID- 2595561 TI - [Brain death criteria. Why is one dead when one is brain dead?]. PMID- 2595562 TI - [Support the desire for nursing education in Greenland]. PMID- 2595563 TI - [Patient complaint tribunal. Only few complain about nurses]. PMID- 2595564 TI - [Nursing under police guard. Interview by Anne Vesterdal]. PMID- 2595565 TI - [Health policy. Decisions must be made in Greenland]. PMID- 2595566 TI - [Education. Translating health strategy for Greenland is our point of departure]. PMID- 2595567 TI - [The clinical forms of disorders of heart rhythm: the formulation of a diagnosis]. PMID- 2595568 TI - [Functional and metabolic activity of lymphocytes in chronic hepatitis, liver cirrhosis and chronic cholecystitis]. PMID- 2595569 TI - [The erythrocyte antioxidant system in chronic liver diseases]. AB - Changes in the antioxidant system of red blood cells may be recorded in chronic liver diseases (persistent and active hepatitis, liver cirrhosis): activation of superoxide dismutase and glutathione reductase, diminution of the activity of total and membrane-bound catalase, of the content of reduced glutathione. In liver cirrhosis, the activity of glutathione peroxidase decreases. The changes in the antioxidant system are accompanied by the reduction of the content of total and membrane-bound protein sulfhydryl groups. PMID- 2595570 TI - [The effect of ultraviolet irradiation of patients' blood on the morphofunctional status of erythrocytes]. AB - The morphofunctional status of red blood cells was studied in patients with terminal renal failure associated with pyo-inflammatory complications treated by means of ultraviolet radiation of autologous blood. The authors have established that ultraviolet radiation of autologous blood results in the increase of the discocyte count and red blood cell activation, evidenced by the rise of the young red blood cell count, of the red blood cell population with marked activity of glucose 6-phosphate dehydrogenase, of the content of sulfhydryl groups, and by the increase of erythrocytic adhesion. PMID- 2595571 TI - [Diagnosis of the initial stage of hypertension based on an assessment of the regulation of cardiac activity in response to physical loading]. AB - A total of 78 men with arterial hypertension (AH) and 33 normal persons were examined for regulation of heart work after exercise. In groups of patients with AH, appreciable differences were discovered in the main parameters of the transitory process. In persons with border-line arterial hypertension (BAH), the transitory process was marked by the increase of the main parameters as compared with normal persons and patients suffering from essential hypertension. As essential hypertension developed, the regulation proceeded in the rigid mode, the main parameters of the transitory process considerably dropped and correlated with the disease stage. No significant differences were discovered in the central hemodynamics in persons with BAH and initial stage of essential hypertension. PMID- 2595572 TI - [Problem-oriented instruction at departments of internal diseases]. PMID- 2595574 TI - [Teaching games in the training of interns in therapeutics]. AB - The paper treats of the problems of knowledge mastering in internal medicine by means of training games. The methodological recommendations are given as to the preparation and performance of the games. Evidence is provided for a wider use of the games for consolidation of the theoretical and practical skills and abilities as well as of the elements of a creative approach to the fulfilling of medical responsibilities. PMID- 2595573 TI - [The method of teaching therapy--the problem approach to diagnosis]. AB - The methodology of a so-called task force approach to the diagnosis is suggested. It determines the strategy of the physician's diagnostic searches in some problems occurring in the examination of patients afflicted with the given disease. The problems (stages, levels of examination) show how one should reason, i. e. they form concrete bases for clinical thinking. According to this methodology, the symptoms should be classified with separate diagnostic problems- trends or stages of the patient's examination at the stage of a probable diagnosis establishment. The task force approach is a method of analysis which prevents potential gross diagnostic errors by means of deciding the main questions (functional, pathogenetic, etc.). A well-defined wording of the above indicated problems--concrete regularities of the clinical thinking--are of paramount importance in teaching therapy. Examples are provided of the task force approach to the diagnosis of pyelonephritis, infectious myocarditis, anemia, and some other diseases. PMID- 2595575 TI - [The certification examination and its role in assessing the level of professional qualification of the therapist]. PMID- 2595576 TI - [Practical problems of the treatment of hypertension]. PMID- 2595577 TI - [Hemodynamics of the greater and lesser circulation in patients with hypertension]. AB - Based on a study of the hemodynamics of the greater and pulmonary circulation by direct methods in 117 patients with essential hypertension it has been demonstrated that changes in the stroke volume are implicated in the mechanism of the interregulation of the greater and pulmonary circulation. Elevation of the pressure in the pulmonary artery is mostly observed in patients with the hypokinetic version of the hemodynamics. PMID- 2595578 TI - [A case of the effective use of plasmapheresis and extracorporeal immunomodulation in treating primary protracted bacterial endocarditis]. PMID- 2595579 TI - [A rare form of immunodeficiency and an attempt to correct it at a polyclinic]. PMID- 2595580 TI - [Morbidity and mortality from stroke among the population of Moscow]. AB - The paper is concerned with the data on the brain stroke incidence and lethality among the population aged 25-64 years in 3 districts of Moscow during 1985. The rate of brain stroke was noted to be increased with age without any essential differences in the indicators in men and women. Comparison of the results of the investigation with the data of the Register, carried out in one of the districts of Moscow during 1972-1973 did not reveal any changes in both the disease incidence and lethality due to brain stroke. The rise of the calls on ambulances and emergency medical service for acute derangement of brain circulation is explained by the authors by a possible growth of the number of the disease cases among senile patients or by aging of the population of Moscow. PMID- 2595581 TI - [Dynamic function of the recanalized coronary artery in patients with myocardial infarct undergoing thrombolytic therapy]. AB - In order to study the efficacy of thrombolytic therapy from the standpoint of preserving contractile function of the left ventricle myocardium, the time course of changes in residual stenosis of the recanalized coronary artery was assessed in 36 patients with myocardial infarction. It has been shown that residual stenosis of the infarction-bound coronary artery determines in many respects the degree of preserving contractile function of the myocardium in cases of successful coronary thrombolysis. In approximately 50% of the cases of the recovery of the coronary blood flow under the action of streptokinase, residual stenosis of the infarction-bound artery regressed by day 28 of the disease. However, contractile function of the left ventricle myocardium may be expected to be preserved during successful thrombolysis only in cases where residual stenosis of the recanalized vessel regresses rapidly (within the first 24 hours since the occurrence of an anginal attack). PMID- 2595582 TI - [An evaluation of the efficacy of using hemosorption in progressive stenocardia]. PMID- 2595583 TI - [Radiokinetocardiography: our first experience in studying the movements of the anterior and lateral walls of the left ventricle in patients with myocardial infarct]. AB - Radiokinetocardiography (RKCG), a noninvasive introscopic technique for studying the heart structures by detecting the echoes from the heart of the electromagnetic ultra-high-frequency signal, has been developed. RKCG was used to record the movements of the anterior and lateral walls of the left ventricle in 14 patients with large-focal myocardial infarction localized in the area indicated and in 30 normal persons. The patients were examined at weeks 4-5 of the disease. In patients with myocardial infarction, RKCG permitted one to identify the zones of hypokinesia, dyskinesia (aneurysm), and the transitory zones between the two ones. The use of RKCG makes it possible to discover unequal contractility in the zone of hypokinesia. RKCG appeared to be an informative technique for examining derangements of the movements of the anterior and lateral walls of the left ventricle in patients who suffered myocardial infarction. PMID- 2595584 TI - [Intermittent claudication and risk factors among men 40 to 59 years of age based on the data of a prospective population study]. AB - A study was made of the prevalence of intermittent claudication (IC) and risk factors among men aged 40 to 59 years and of the acute myocardial infarction lethality and incidence during ten years of the follow up. Using standard techniques a representative group of 6117 men were examined. The prevalence of IC amounted to 0.89% in the group under study (standardized according to age). Analysis of the relationship between the prevalence of IC and risk factors has demonstrated the presence of the significant correlation only among men with hypercholesterolemia and tobacco smokers. In men who suffered myocardial infarction, the rate of IC was higher than in men with angina pectoris of effort, painless coronary disease or without coronary disease. Analysis of the acute myocardial infarction lethality and incidence has shown that they are significantly higher among men with IC than in those without this pathology. PMID- 2595585 TI - [The prognosis of fatal outcome in the late period after myocardial infarct]. AB - A method for life prediction within 2 nearest years after myocardial infarction has been designed. For this purpose altogether 922 men who suffered myocardial infarction were examined. The examination included collection of the disease history data, delineation of the characteristics of the patient's status 6 weeks after M1, and performance during that period of the standard bicycle ergometry test. The deciding rule of prediction has been developed. The rule is based on the mathematic discrimination and the use of the so-called "sign blocks" including not only the clinically significant signs such as myocardial infarction in the anamnesis, disability before MI, the signs of heart failure and the grave functional class 6 weeks after MI but also little significant signs (left ventricle hypertrophy, the mean exercise tolerance (up to 600 kgm/min), and so forth), which acquire the prognostic weight when combined with other signs. This deciding rule of prediction with the use of exclusively accessible information turned out to be reliable during work, making it possible to stratify the patients into groups with the practically 100-percent survival up to the high risk of lethality exceeding the mean death rate 4-5-fold. The rule can be applied to public health practices during the use of the "sign blocks" tables. PMID- 2595586 TI - [The role of changes in central and intracardiac hemodynamics in lowering the physical work capacity of patients with ischemic heart disease and diabetes mellitus]. AB - The data of bicycle ergometry test and echocardiography were studied and compared in patients with postinfarction cardiosclerosis and type II diabetes mellitus without the clinical signs of heart failure. The patients showed the decreased work fitness and the identity of cardiovascular responses to graded exercise, pointing to the common character of the pathogenesis of these diseases. Both groups of the patients manifested the hyperkinetic type of the central hemodynamics as well as the lowering of the rate of diastolic relaxation and the rise of the end diastolic volume of the left ventricle. The intracardiac hemodynamics of coronary heart disease was characterized, in addition, by the reduction of myocardial contractility of the left ventricle due to focal injuries to the myocardial structures, which are more pronounced than in diabetes mellitus. PMID- 2595587 TI - [Characteristics of the action of modified atherogenic-class lipoproteins on the functional activity of peripheral blood lymphocytes in patients with ischemic heart disease]. AB - In a study of the effect of lipoproteins of atherogenic classes on proliferative activity of peripheral lymphocytes in patients (n = 44) with ischemic heart disease (IHD) and healthy subjects (n = 16), VLDL isolated from hyperlipidemia blood were shown to have a more suppressive effect on proliferation of PHA induced lymphocytes than those from healthy subjects. Effect analysis of VLDL isolated from patients with different hyperlipidemia types revealed that VLDL obtained from high triglyceride plasma depressed proliferation 85-75%, while VLDL withdrawn from high cholesterol plasma 45-55% (p less than 0.05). With addition of modified (oxidized) VLDL to PHA-activated lymphocytes oxidized VLDL were demonstrated to have a greater inhibitory effect as compared with intact VLDL. The observed peculiarities of the VLDL effect in hyperlipidemia may underlie the reduced functional activity of lymphocytes, discovered in IHD patients (n = 81). PMID- 2595589 TI - [Evaluation of the efficacy of a course of verapamil and nifedipine in patients with stable stenocardia by daily monitoring of the electrocardiogram]. AB - The daily ECG monitoring was used in 20 patients with stable functional class II III angina pectoris to study the antianginal and anti-ischemic effects of verapamil and nifedipine during the cross use of the drugs. Verapamil and nifedipine applied in the effective doses provoked a significant decrease of the number and total depth of painful depressions of the ST segment. The effect of verapamil on painful episodes of ST segment depressions was significantly more pronounced than that of nifedipine. At the same time nifedipine significantly reduced the number and total depth of painless episodes of myocardial ischemia whereas verapamil did not cause any significant lowering of these indicators. In cases where the drugs appeared ineffective, verapamil provoked a significant increase of the number of painless episodes of myocardial ischemia. This indicates that the painful threshold of sensitivity may change with the occurrence of myocardial ischemia in patients suffering from angina pectoris. In turn, nifedipine produced no significant effect on the number and intensity of painless episodes of myocardial ischemia. PMID- 2595588 TI - [The pathogenesis of heart rupture in myocardial infarct]. AB - Examination of 166 patients with primary transmural myocardial infarction (MI) of the anterior site has shown that the blood of MI patients (n = 34) complicated by cardiorrhexis manifests the maximal increase of the stress reaction components, lipid peroxidation products and an appreciable lowering of the content of adaptogens. It is emphasized that the development of the maladaptation syndrome underlies the pathogenesis of cardiorrhexis during MI as the result of the failure of the compensatory-adaptive potentialities of the body in response to the excessive stress reaction. It has been discovered that the high rise of the ST segment on the ECG and pronounced arterial hypoxemia are informative indicators mirroring the high probability of cardiorrhexis occurrence in MI patients. A scheme of cardiorrhexis pathogenesis in MI patients is offered. PMID- 2595590 TI - [The nature of changes in central hemodynamics and myocardial contractile capacity of the left ventricle during volumetric loading in patients with chronic alcoholism in relation to the duration of alcohol abuse]. AB - Forty patients aged 33 to 66 years suffering from chronic alcoholism, stages II III, were examined. All the patients were subjected to contrast ventriculography before and after exercise test to identify the latent forms of heart failure. According to the coronarography findings, 9 out of the 40 patients demonstrated the signs of atherosclerotic injury to the coronary arteries. The data of endomyocardial biopsy of the left ventricle have shown morphologic changes characteristic of alcohol-induced heart injury, namely atrophy of cardiomyocytes, fat deposition in the interstitium, lysis of myofibrils, appearance of large vacuoles in cardiomyocytes, and mitochondriosis. PMID- 2595591 TI - [Assessment of the diagnostic value of myocardial scintigraphy with 201Tl chloride in women of various ages]. AB - Myocardial scintigraphy with the use of 201-thallium was performed in 92 female patients aged 38 to 87 years (initially and after 24 hours). The menstrual cycle phases were revealed to influence perfusion and metabolism of the myocardium in women with the normal ovarian cycle which should be taken into consideration in the interpretation of scintigrams in young women. The results of examining elderly persons with a long menopause have demonstrated excess saturation of scintigrams, both initial and long-term, which is primarily determined by changes in the coronary bed by the three-vascular injury type and hypertrophy of the left ventricle myocardium. PMID- 2595592 TI - [Heart involvement in hypereosinophilia: the restrictive or the dilated type?]. AB - As many as 60 patients with hypereosinophilia of different genesis were examined. 40 of them manifested the clinical (congestive heart failure in 6, tachycardia in 10, cardialgias in 3, murmur in the heart in 13, pericardial murmur in 3) and/or ECG signs (disorders of repolarization in 25, His bundle block in 4, rhythm disorders in 7, pathologic Q waves in 2) of heart injury. In 15 out of the 20 examined, the echocardiography data corresponded to the dilated pattern of heart injury despite the fact that the changes in contractile function of the left ventricle were less appreciable than in 28 patients with dilated cardiomyopathy. In 2 patients who died (one from congestive heart failure and one from anaphylactic shock) the presence of endomyocardial fibrosis with heart dilatation was confirmed on postmortem examination. One female patient with right ventricular failure manifested the characteristic signs of isolated injury to the right ventricle. In 3 patients, the endocardium appeared thickened. None of the cases showed the signs of restrictive heart injury. The data obtained indicate that hypereosinophilia may be one of the etiologic factors of dilated cardiomyopathy. PMID- 2595593 TI - [Comparative characteristics of the arrhythmic syndrome and the possibility for its coenzyme correction in dilated and hypertrophic cardiomyopathy]. AB - Disorders of heart rhythm and conduction were characterized clinically and by electrocardiography in 82 patients with dilated and hypertrophic cardiomyopathies. Based on an analysis of blood lymphocyte cytochemistry energy deficient conditions of the myocardium were identified in the patients examined. In order to correct the metabolic shifts in the myocardium, use was made of a coenzymic medicamentous complex including pyridoxalphosphate, cobamamide and phosphadene. The complex indicated was shown to potentiate the action of antiarrhythmic agents employed in the treatment of idiopathic cardiomyopathies. PMID- 2595594 TI - [Normal intracardiac flow in middle-aged subjects based on Doppler echocardiographic data]. AB - Doppler's echocardiography was employed in 25 healthy persons aged 26 to 38 years to establish that normal flows from the atrioventricular valves (two-peak and diastolic ones) are directed towards the monitor. The first peak (of early filling) shows on the synchronously recorded electrocardiogram a certain period after the T wave occurrence, whereas the second one (of later filling) after the P wave. The flow from the tricuspid valve varied with respiration. In 8 persons (32%), the systolic turbulent flow was recorded in the ostium of the tricuspid valve and in one person, in the ostium of the mitral valve. The velocity of the flows did not exceed 2 m/s. The flows via the main vessels (aorta and pulmonary artery) were of one peak and systolic. The spectrum of the aortal flow was more pointed and reached the maximum velocity more rapidly. In the efferent tract of the left ventricle, no reverse diastolic flow was obtained, whereas in the efferent tract of the right ventricle, it could be obtained in 15 persons (60%). The velocity of the flow did not exceed 1 m/s. The maximum and integral velocities of the flow via the mitral valve exceeded those of the flow via the tricuspid valve. Besides, the flows were different as regards the magnitude of the mean acceleration and the mean deceleration of the early filling of the ventricles. The velocities of the flow in the aorta exceeded those of the pulmonary flow. The phase of the pulmonary flow acceleration accounted for 40.7% of expulsion, that of the aortal flow only for 29%. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2595595 TI - [Experience in using echocardiography at a district diagnostic center]. AB - The authors studied the data of echocardiography performed at the district diagnostic center rendering services for 337000 adult population. Altogether 487 patients were referred to the center for echocardiography. The main portion of the patients included 398 persons (81.7%) with suspected heart disease and prolapse of one of the cusps of the mitral valve. 326 persons (66.7%) were under 39 years. The experience in the use of echocardiography under the conditions of the specialized polyclinics (the diagnostic center) has shown the high efficacy of the technique during examination of the patients at the prehospital stage. PMID- 2595596 TI - [The importance of the noninvasive determination of the anaerobic threshold for assessing the heart pumping function in patients with mitral and aortic heart defects]. AB - The anaerobic threshold (AT) was determined in 68 patients suffering from heart disease and in 18 normal persons during the treadmill test according to the parameters of ventilation and gas exchange. The dynamics of the oxygen debt was assessed in accordance with the dynamics of the recovery coefficient (RC). It was established that in the assessment of pump function of the heart, the sensitivity of the RC was 89%, that of the AT 51%. It was also found that the AT, as an indicator of the decompensation of pump function of the heart, can only be used in patients belonging to functional classes IV and III. PMID- 2595597 TI - Proboscis lateralis: a case report. AB - A lateral proboscis usually occurs in the region of the inner canthus. We present a case of holoprosencephaly accompanied by an oblique facial cleft and an anterior encephalocele in which a proboscis lateralis occurred in a very lateral location. PMID- 2595598 TI - In vitro developmental toxicity of five direct-acting alkylating agents in rodent embryos: structure-activity patterns. AB - Five direct-acting alkylating agents were examined qualitatively and quantitatively for their ability to produce developmental toxicity in rodent postimplantation embryos. These agents were structurally related and were capable of donating either a methyl (methylnitrosourea, MNU; methylnitronitrosoguanidine, MNNG; methyl methanesulfonate, MMS) or ethyl (ethylnitrosourea, ENU; ethyl methanesulfonate, EMS) group to nucleophiles. These agents' reactivities were known to differ. In day 10 rat embryos in vitro a single, 2-hour exposure was shown to be sufficient to elicit dose-dependent increases in embryo lethality and malformations. Qualitatively, the patterns of embryo malformations reported in treated embryos paralleled those observed in in vivo studies, especially in regard to adverse effects on central nervous system and craniofacial systems. Quantitatively, the order of potency of these agents in vitro was: MNNG greater than MNU greater than ENU greater than MMS greater than EMS. In vivo studies reported a different order of potency. In vitro, methylating agents were consistently more potent than ethylating agents. Other chemical properties such as nucleophilic reactivity or half-life under physiological conditions could not explain observed potency relationships. Future investigation of other chemical properties of these agents such as specific alkylation and carbamylation reactivities may expand these initial structure-activity observations. PMID- 2595599 TI - Morphological and physiological effects of beta-hydroxybutyrate on rat embryos grown in vitro at different stages. AB - Diabetic women are more likely to give birth to infants with congenital malformations than are nondiabetic women. Rodent embryos have been used as a model for the study of abnormal fetal development associated with maternal diabetes, and some of the metabolic factors which are altered in diabetes, such as raised glucose and ketones, have been shown to cause abnormal development of rodent embryos in vitro. The present work explores further the teratogenicity of beta-hydroxybutyrate to rat embryos. To determine the sensitivities of rat embryos at different stages of their development, rat embryos at 9.5 days of gestation have been cultured in vitro for 24 or 48 h, with or without 4 x 10(-2) M beta-hydroxybutyrate for all or part of the culture period. The embryos have been examined by scanning electron microscopy, and a detailed morphometric analysis of one tissue, the neuroepithelium, has been undertaken. The results confirm that beta-hydroxybutyrate causes abnormal development of rat embryos. The results of experiments in which embryos were exposed to beta-hydroxybutyrate for only part of a 48 h culture show that embryos exposed to beta-hydroxybutyrate for a complete 48 h culture are more severely affected than embryos exposed to beta hydroxybutyrate for only part of the culture and that embryos are more vulnerable to beta-hydroxybutyrate during the first half of a 48 h culture (equivalent to 9.5 to 10.5 days of gestation) than during the second half of a 48 h culture (10.5 to 11.5 days of gestation). The results of experiments in which embryos were cultured with beta-hydroxybutyrate from 9.5 days of gestation for 24 h (equivalent to 9.5 to 10.5 days of gestation) showed that some effects of beta hydroxybutyrate are already apparent after 24 hours in culture. Many of the abnormalities produced by beta-hydroxybutyrate can be classified as embryonic retardations rather than malformations--that is, embryos show features characteristic of normal, but younger, embryos. Embryos exposed to beta hydroxybutyrate for the complete 48 h culture period consume less glucose and produce less lactate than control embryos on a per embryo basis, but not on a per microgram protein basis, suggesting that the reduced metabolism is an effect of beta-hydroxybutyrate-induced developmental delay rather than a cause of it.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2595600 TI - The AMA alternative to medical liability litigation: pros, cons, and fatal flaws. AB - The AMA proposal for an administrative scheme to replace professional liability litigation has many positive features. It abolishes jury trial and allows administrative determination of fault, representation by appointed lawyers, and limited recovery but for a wider range of injuries during treatment. Attractive as these provisions may seem to medical providers, several of them are radical enough to ensure rejection by the courts as unconstitutional. The "total package" approach to professional liability reform is less promising than concentration on the introduction of a few key items of proven or probable efficacy. Medical providers should concentrate their limited resources on tort reform providing for "caps" on noneconomic damages (pain and suffering), an absolute statute of limitations, reversal of the collateral sources (double recovery) rule, limitations on attorneys' fees, and periodic payments, rather than lump sums, for large awards. The new TMA proposal for neurological birth injuries is discussed briefly. PMID- 2595601 TI - Cardiovascular mortality trends in Harris County, Texas: 1980 to 1986. AB - Cardiovascular diseases are the leading causes of death in Texas and in the United States. This study determines the trend in mortality rates attributed to cardiovascular diseases in Harris County from 1980 to 1986. The region of the county that does not include the City of Houston was specifically studied. Mortality of cardiovascular diseases in these two areas follow patterns similar to that of the United States in the same time period. Both the entire county and Harris County excluding Houston show declines in cardiovascular mortality rates in the 7-year period. The populations were divided into four ethnic categories (white, black, Hispanic and "other"), and each ethnic group reported significant declines in overall cardiovascular mortality except in the "other" population, which showed an increase in the male group. Significant downward trends were noticed in the white and Hispanic population in the two major subcategories of cardiovascular diseases: diseases of the heart and cerebrovascular diseases. The black population in each geographic area studied was consistently higher in cardiovascular mortality than the other three ethnic groups observed (white, Hispanic and "other"). Knowledge of cardiovascular disease mortality rates by ethnicity, sex, and age as well as temporal changes in mortality rates within Harris County are important for health planners in continuing and implementing programs aimed at awareness, prevention, and treatment of cardiovascular diseases. PMID- 2595603 TI - Let's make Texas drug-free. PMID- 2595602 TI - Tuberculosis in San Antonio: 1960-1984. AB - San Antonio, Tex, has a long history of having a high rate of tuberculosis, but from 1960 through 1984, the rate was reduced by 82.6%. In 1984 it had a lower case rate than all but one of the six major Texas cities. The rate reduction involved all ethnic groups. The City Chest Clinic treats most of the new active cases, either by providing all necessary services or by supplying medication in cooperation with local physicians. The use of chemotherapeutic drugs has greatly reduced the transmission of the disease. Preventive therapy may prevent infection or reduce the bacterial population in contacts of active cases. The city health department's nursing division provides follow-up of patients and contacts. To prevent premature discontinuation of medications, nurses observe selected patients as they take their medicines. High case rates among minority ethnic groups, although improved, still are observed. Furthermore, high rates of new active cases are still found in areas of the city with the lowest median family income, low median values of homes, and overcrowding. PMID- 2595604 TI - Texas will see red during Drug Free America Week. AB - Betty Haisten is the living image of refinement. But that doesn't stop her from cornering the manager of a cafeteria in her hometown of Beaumont and putting pressure on him to use his facility as a distribution point for red ribbons encouraging patrons to "Join me--I'm drug free." She is a woman with a cause, a moving force behind Drug Free America Week in Texas. And, with the members of the nation's largest medical association auxiliary and their spouses behind Mrs. Haisten, Texas will see red--red ribbons--Oct 22-29. The Texas Red Ribbon Campaign is designed to establish a coalition in every community in support of drug-free lifestyles. This article describes how Texas Medical Association and TMAA are supporting the campaign's goal. PMID- 2595605 TI - 1989 AIDS update. AB - The leadership of the 70th Texas Legislature (1987) created the Legislative Task Force on AIDS to study the impact of AIDS in Texas and to recommend to the 71st Legislature (1989) public policies needed to reduce the impact of AIDS in Texas. The task force held numerous public hearings and received testimony from witnesses involved with all areas touched by AIDS. The task force also surveyed state agencies, health care entities, and met with statewide associations, including the Texas Medical Association. A Statement of Preliminary Findings was released in August 1988, and a Final Report was issued in January 1989. Many of the task force's recommendations became part of the Omnibus AIDS Bill filed in the 71st Legislature. After much discussion and public controversy, Senate Bill 959 was passed and took effect Sept 1, 1989. Known as the "Human Immunodeficiency Virus Services Act," it amends numerous statutes and creates new requirements. This article (1) answers a number of questions physicians have raised about how the new law affects their practices. PMID- 2595606 TI - Cholesterol education implications for clinical practice. AB - It is well established that an elevated plasma cholesterol level is a major risk factor for coronary heart disease (CHD). Furthermore, results from several clinical trials indicate that therapeutic reduction of high-risk plasma cholesterol levels is followed by a reduction in CHD risk. The National Cholesterol Education Program (NCEP) was launched to enhance the detection of individuals with increased risk for CHD due to elevated plasma cholesterol levels, and to provide guidelines to clinicians for the detection, evaluation and treatment of these high-risk individuals. The key features of the NCEP are described and the guidelines for the detection, evaluation and treatment of high blood cholesterol in adults are summarized. Appropriate treatment of high-risk individuals includes reduction of elevated cholesterol levels and control of other cardiovascular risk factors. Diet therapy is the first step in control of elevated plasma cholesterol levels. In high-risk individuals who do not respond adequately to diet therapy, drug treatment should be considered. Clinical judgment must be used to individualize treatment in each patient. Better detection and control of elevated cholesterol levels and other cardiovascular risk factors should spare high-risk individuals from morbidity and mortality associated with premature CHD. PMID- 2595607 TI - Quick reference to National Cholesterol Education Program: adult cholesterol treatment guidelines. PMID- 2595609 TI - Infant circumcision in an outpatient setting. AB - We conducted a retrospective evaluation of 442 infant circumcisions performed in an ambulatory setting. Procedures done with the Gomco clamp (Gomco Division, Allied Health Care, Buffalo, NY) and the Plastibell device (Hollister, Inc, Libertyville, Ill) were compared with respect to the frequency of complications. The overall complication rate was 6.8%. Bleeding requiring action by a physician occurred in 3.4% of cases and was significantly more common with the Gomco clamp than with the Plastibell device (p less than 0.05). There were no statistically significant differences between the two methods in the rate of infection or other complications. The rate of complications is comparable to previous studies of inpatient circumcision. PMID- 2595608 TI - Pediatric AIDS: clinical presentation and diagnosis. AB - HIV infection/AIDS in infants and children under the age of 13 years expresses itself clinically so differently from the same infection in adults that a separate classification of the symptomatology has been adopted. Recurrent bacterial infections, as well as various opportunistic infections predominate, and while Kaposi's sarcoma is infrequent in pediatric patients, lymphomas occur with high frequency. The diagnosis of HIV infection/AIDS in children is presented. PMID- 2595610 TI - Cholesterol education program offers guidelines. PMID- 2595611 TI - Parasitic infections in Asian refugees in Fort Worth. AB - This report describes parasitic infections recorded from April 1984 to December 1987 in refugees using services of the Fort Worth-Tarrant County Public Health Department. Infections with 1,601 parasitic infections were documented in 824 laboratory specimens obtained from refugees. Ascariasis and giardiasis were more prevalent than other parasitic infections. The highest attack rates occurred in refugees from Cambodia (70.0%), Laos (69.7%), and Vietnam (54.3%). Information from this study supports published data on high attack rates and endemicity of infections in refugees from Southeast Asia. Continued surveillance and treatment of these refugees should improve their health conditions and prevent the development of endemic foci in the United States. PMID- 2595612 TI - New laws on patient treatment decisions. AB - These recent legislative changes should assist physicians in implementing appropriate health care decisions by patients and their families. The Natural Death Act amendments authorize the withholding and withdrawal of life-sustaining procedures from patients with incurable or irreversible conditions if death will result within a relatively short time without use of such procedures. The amendments are effective Sept 1, 1989, and apply to directives executed on or after that date. The durable power of attorney bill, effective June 14, 1989, provides a comprehensive method for allowing decision making by a surrogate. Education of the public and advance planning by principals are needed for it to be effective. Because HB 2098 requires advance execution of the power of attorney, in all likelihood most decisions to withhold or withdraw life sustaining procedures from patients with a terminal condition will continue to be made using the procedures set forth in the Natural Death Act. PMID- 2595613 TI - [Concept: occupational medicine 2000]. AB - The group of physicians practising occupational medicine in Switzerland is actually still small, and it will need a very important development to reach, on a nation-wide base and not only within a few large companies, a standard of occupational medicine which satisfies from a social security as well as from an economical point of view. The occupational medicine has, therefore, to elucidate to the social partners and to the public the benefit for health and public welfare of its preventive activity at the workplace. The following goals are thus to be pursued: Further development of a legal basis in Switzerland equal to the standard of the neighbouring countries of the European Community Provision of sound models assuring occupational medical care of all business, in particular of the small and middle-sized business Promotion of student's education, specialist formation and continuative schooling in occupational medicine Provision of an adequate university teaching and research capacity with firm links to the practice A more powerful and competent representation of occupational medical aspects in actual discussions of health legislation and social legislation. PMID- 2595614 TI - [Employee protection and occupational medicine in Switzerland. Legal and organizational aspects]. AB - The regulations aimed at protecting the health of workers are essentially contained in both the Labour Law (general hygiene, duration of work and rest periods, special protection of women and minors) and in the Law Governing Accident Insurance (prevention of accidents and professional illnesses). The employer is obliged to take all the necessary measures for the protection of his employees and to ensure the collaboration of the latter to this end. The National Insurance together with the federal and cantonal Labour Law enforcement agencies share the task of supervising the application of legal health protection. In particular, the National Insurance and the Confederation have a medical service at their disposal. In order to comply with requirements, large firms have their own health and safety service, some with an industrial physician. An ordinance which will oblige high risk firms or firms above a certain size to have resident industrial physicians as well as other labour safety specialists is at present being discussed. One of the aims of the proposed revision of the Labour Law is an improvement in the medical supervision of workers exercising their profession at night. PMID- 2595615 TI - [Working women and the health of female workers]. AB - Working women in Switzerland are rarely exposed to severe occupational injuries and diseases, just because they are not employed in hazardous industries, such as the building industry. It does not mean unfortunately, that the type of work which is mostly offered to them is pleasant and comfortable. Bad and stressful working conditions are very common in traditional industries such as the textile or the food industry. Moreover, the new technology introduced more constrain in underqualified jobs, such as high working speed and prolonged sitting posture. For the family physician, it is thus very important to take care of the health of unskilled female workers. As far as female executives are concerned, they do not need any medical help; to work is for them a pleasure and they know perfectly well when and why they need to visit their physician. PMID- 2595616 TI - [The rehabilitation hiatus]. AB - A gap its often to be found between medical rehabilitation after a disease or accident and professional reintegration. Causes and consequences as well as means of preventing it are being shown. PMID- 2595617 TI - [First aid for irritant gas inhalation in an industry]. AB - The inhalation of irritant gases, fumes or dusts may, depending upon the chemical nature of the irritant and upon intensity and duration of the exposure, produce an irritation of the respiratory tract, a toxic pneumonitis (lung oedema) or both. A treatment with corticosteroids by inhalation started immediately is active in reducing the respiratory irritation and in preventing the patient from developing a toxic pneumonitis. The paper presents a logistic model for industrial plants to apply that effective treatment (this includes: in time) to all such patients who need it. PMID- 2595619 TI - Second primary lung cancer: importance of long term follow up. AB - Review of histopathological and clinical data showed that 153 patients at one hospital developed a second primary lung cancer during 1980-6, 10% of all those with lung carcinoma. There were 64 synchronous tumours (interval less than one year) and 89 metachronous tumours (interval over one year). The average interval between metachronous tumours was 6.1 years. The criteria for diagnosing a second primary lung cancer were any of the following: (1) different histological type; (2) different lobe; (3) interval between the two tumours of at least three years. The incidence of second primary tumours increases with survival, and close follow up is required for their early detection. PMID- 2595618 TI - AIDS and the lung. Introduction. PMID- 2595620 TI - Comparison of the Tru-cut biopsy needle with the Abrams punch for pleural biopsy. AB - In a prospective study pleural biopsy specimens obtained with a Tru-cut needle were compared with those obtained with an Abrams pleural biopsy punch from 36 patients in Zimbabwe judged to have an effusion of at least 1.5 litres; one patient had two biopsies. Both instruments were used on each patient, the Abrams punch being followed by the Tru-cut needle. There were no serious complications. The diagnoses determined by biopsy were: tuberculosis (11); carcinoma (12); chronic inflammation (9); and pleural fibrosis (4); one biopsy showed nothing abnormal. In 23 (62%) patients both biopsy needles produced adequate diagnostic material; in eight the Tru-cut needle alone produced diagnostic material and in six the Abrams punch alone. Thus diagnostic material was obtained in 31 patients from the Tru-cut needle and in 29 from the Abrams punch. The Tru-cut needle was useful and safe for pleural biopsy in this series and appeared to be particularly useful when the pleura was thickened. PMID- 2595621 TI - Treatment of adult asthma: is the diagnosis relevant? AB - The diagnosis and management of chronic respiratory symptoms was studied in all adults aged 40-70 years in a group general practice. A respiratory symptoms screening questionnaire was sent to 2387 men and women, of whom 1444 (85% of those who had not moved or died) responded. The 509 subjects reporting symptoms were sent a detailed questionnaire and invited to have their respiratory function tested. Of these, 324 (64%) responded, of whom 256 (79%) had spirometry. A diagnosis of chronic bronchitis was reported by 3.9% of the men and 2.1% of the women, and a diagnosis of asthma by 4.7% of the men and 3.3% of the women. Wheezing in the preceding year was reported by 18% of the men and 15% of the women, and 16.7% of the men and 7.1% of the women satisfied the Medical Research Council criteria for chronic bronchitis. Bronchodilator treatment was being taken by 12% of the patients with symptoms, regular cough linctus by 10%, and regular antibiotics by 5%. After the frequency and severity of respiratory symptoms had been controlled for wheezing patients reporting a diagnosis of asthma were prescribed bronchodilatory drugs three times more often than those labelled as having chronic bronchitis and 12 times more often than those without a diagnostic label. Eleven per cent of general practitioner consultations resulted in a referral to hospital. Referral was unrelated to the diagnosis given, but depended on the degree of respiratory disability and handicap experienced by the patient. Our findings confirm the relevance of the diagnostic label to the drug management of chronic wheezing disorders, but further investigation of the diagnostic process is needed to establish why some patients with severe wheeze remain untreated. PMID- 2595623 TI - Contractility of papillary muscle from rats exposed to 28 days of hypoxia, hypercapnia, and hypoxia with hypercapnia. AB - The effects of chronic respiratory failure (hypoxia and hypercapnia) on the contractile properties of cardiac muscle are not established. A study was performed of the isometric contractile properties of isolated papillary muscle removed from rats exposed in a normobaric environmental chamber to 28 days of hypoxia (fractional inspired oxygen (FIO2) 10%, fractional inspired carbon dioxide (FICO2) less than 1%), hypercapnia (FIO2 21%, FICO2 5%), and hypoxia with hypercapnia (FIO2 10%, FICO2 5%). Rats exposed to both hypoxia and hypoxia with hypercapnia developed selective right ventricular hypertrophy. Exposure to hypercapnia alone did not alter right ventricular weight. No change in right ventricular papillary muscle contractility per unit muscle mass was observed as measured by maximum active tension, maximum rate of rise or fall of tension, or time to peak tension. Rat cardiac muscle adapts successfully to the altered acid base environment and increased work load associated with prolonged exposure to hypoxia and mild hypercapnia. PMID- 2595622 TI - Circadian change in bronchial responsiveness and airflow obstruction in asthmatic children. AB - To throw light on the question of whether the increase in bronchial responsiveness seen during the night is due to increased airflow obstruction, nine asthmatic children with increased airflow obstruction at night (group 1) were compared with nine without (group 2). The mean fall in forced expiratory volume in one second (FEV1) between 16.00 and 04.00 hours was 21.9% in group 1 and 2.3% in group 2. Selection of patients was based on the amplitude of change in peak expiratory flow (PEF) measured every four hours for three consecutive days at home. The study was performed in hospital on four consecutive days. Medication was withheld for three days before and during the measurements at home and in hospital. On the first day in hospital (day 4) FEV1 was measured every four hours for 24 hours. On day 6 inhaled histamine provocation tests were performed at the same times as the FEV1 measurements on day 4. Both groups showed a nocturnal fall in the provocative dose of histamine causing a 20% fall in FEV1 (PC20). The mean change in histamine PC20 from 16.00 to 04.00 hours was 1.1 doubling doses of histamine in group 1 and 1.5 doubling doses in group 2. The results indicate that the increase in nocturnal bronchial responsiveness that occurs at night is not due to an increase in airflow obstruction. PMID- 2595624 TI - Bronchoscopy findings in invasive pulmonary aspergillosis. AB - Two patients with invasive aspergillosis had unusual endobronchial appearances at fibreoptic bronchoscopy. Diagnosis was achieved by endobronchial biopsy. PMID- 2595625 TI - Bilateral recurrent haemorrhagic pleural effusion in asymptomatic chronic pancreatitis. AB - In a case of bilateral recurrent haemorrhagic pleural effusion due to asymptomatic pancreatitis the diagnosis was suggested by the presence of amylase in the pleural fluid when other possible causes had been excluded. Abdominal computed tomography and laparotomy confirmed the diagnosis. No communications could be seen between the peritoneal and pleural space at laparotomy. PMID- 2595626 TI - Dissemination of tumour cells from fine needle biopsy. AB - A 53 year old woman developed a cutaneous tumour implant in the needle track after transcutaneous fine needle biopsy of a pulmonary adenocarcinoma. The tumour implant was completely excised. PMID- 2595627 TI - Sarcoidosis in an adult with cystic fibrosis. AB - Sarcoidosis in an adult patient with cystic fibrosis lung disease was diagnosed on the basis of pulmonary function and radiographic data. It should be considered in the differential diagnosis of new diffuse interstitial infiltrates or hilar adenopathy in a patient with cystic fibrosis; biopsy of lung, lymph node, or skin lesions and interleukin-2 receptor levels may help to obtain a diagnosis. PMID- 2595628 TI - Nebulised pentamidine as treatment for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. PMID- 2595629 TI - Proceedings of the British Thoracic Society. 12-14 July 1989, University of Southampton. Abstracts. PMID- 2595630 TI - Inspiratory and skeletal muscle strength and endurance and diaphragmatic activation in patients with chronic airflow limitation. AB - To determine whether patients with chronic airflow limitation have a specific alteration in skeletal muscle performance, the strength and endurance of inspiratory and limb muscles were compared in 11 patients with chronic airflow limitation and 11 control subjects during maximal voluntary contractions. Peak inspiratory pressure at observed functional residual capacity (FRC) was significantly less in the patients than in the control subjects (mean 72 (SD 25) v 93 (21) cm H2O), though only two patients had low maximal pressures across a wide volume range. Maximal voluntary torque of the elbow flexor muscles was also reduced in the patients but the difference was not significant (60 (17) v 72 (18) Nm). During the endurance sequence of 18 maximal voluntary contractions (10 s duration, 5 s rest interval) the decline in peak and average force was less for the inspiratory muscles than for the elbow flexors in both groups. Inspiratory muscle endurance was slightly greater in the patients with chronic airflow limitation than in the control subjects, whereas limb muscle endurance was slightly impaired in the patients. In three patients with chronic airflow limitation, two of whom had low maximal inspiratory pressures at FRC, the ability to drive the diaphragm voluntarily was examined by stimulating the phrenic nerves during maximal inspiratory efforts. Each patient was capable of full activation of the diaphragm during the maximal inspiratory efforts. These results suggest that the relative preservation of inspiratory muscle performance in patients with chronic airflow limitation may be an adaptive response to respiratory "loading." PMID- 2595631 TI - Respiratory muscle weakness in the Lambert-Eaton myasthenic syndrome. AB - Respiratory muscle function was assessed in six patients with the Lambert-Eaton myasthenic syndrome. Five had histologically proved small cell carcinoma of the lung; the sixth later developed metastases from an unknown primary site. Two patients had ventilatory failure, one without respiratory symptoms; another, who had emphysema, had dyspnoea and orthopnoea. The remaining three patients had no respiratory symptoms. Four patients had limb muscle weakness as judged by the maximal voluntary contraction of the quadriceps muscle (range for all subjects 32 100% predicted). Transdiaphragmatic pressure (Pdi) was measured during a maximal unoccluded sniff (Pdi: sniff), a maximal sustained inspiratory effort against a closed airway (Pdi: Pimax), and phrenic nerve stimulation (Pdi: twitch). Mild to moderate diaphragmatic weakness was present in all six patients in proportion to the degree of leg weakness (Pdi: sniff 30-64% predicted; r = 0.6; Pdi:Pimax 6-69% predicted, r = 0.8); this was associated with very low or absent Pdi:twitch during phrenic nerve stimulation. Four patients had weakness of the expiratory muscles. Improvement in muscle strength was documented in two patients after tumour chemotherapy and specific treatment with 3,4-diaminopyridine and prednisolone; one patient was still alive five years from first diagnosis. It is concluded that the respiratory muscles may be implicated in this condition more often than has previously been recognised. As the lack of mobility may cause respiratory symptoms to be minimised, the presence of respiratory muscle weakness may remain undiagnosed unless formal measurement of respiratory muscle function is made. PMID- 2595632 TI - Pulmonary eosinophilia with and without allergic bronchopulmonary aspergillosis. AB - Sixty five patients with pulmonary eosinophilia attending one respiratory unit were reviewed. All had fleeting radiographic abnormalities and peripheral blood eosinophil counts greater than 500 x 10(6)/l. Eighteen had a single episode and 47 recurrent episodes during a median follow up period of 14 years. Thirty three patients had allergic bronchopulmonary aspergillosis on the basis of a positive skin test response to Aspergillus fumigatus, serum precipitins, or culture of A fumigatus from sputum, or a combination of these. All but seven patients had asthma, six of the seven being in the group who did not have allergic bronchopulmonary aspergillosis. The patients with allergic bronchopulmonary aspergillosis were more often male and had a greater incidence of asthma and an earlier age of onset of asthma than those without aspergillosis. The patients with aspergillosis had lower mean blood eosinophil counts and more episodes of pulmonary eosinophilia and more commonly had radiographic shadowing that suggested fibrosis or bronchiectasis (20 v 7). Pulmonary eosinophilia associated with allergic bronchopulmonary aspergillosis appears to be a distinct clinical syndrome resulting in greater permanent radiographic abnormality despite lower peripheral blood eosinophil counts. PMID- 2595633 TI - Corticosteroid treatment and prognosis in pulmonary eosinophilia. AB - The acute and long term responses to corticosteroid treatment in 65 patients with pulmonary eosinophilia have been reviewed. Of the 247 episodes of pulmonary eosinophilia that were documented during a median follow up period of 14 years, 186 were treated with prednisolone. Complete clearing of chest radiographic infiltrates occurred in 65% of the 247 episodes, partial clearing in 25%, and no response in 9%. Blood eosinophil counts were monitored during 194 episodes and returned to normal in 72%, decreased in 19%, and remained raised in 9%. Complete radiological clearing and a reduction in blood eosinophil counts were more common in episodes treated with prednisolone. Long term prednisolone was given to 28 of the 33 patients with allergic bronchopulmonary aspergillosis (mean 7.4 mg/day for 11 years) and to 29 of the 32 "non-aspergillosis" patients (mean 8.1 mg/day for 4.6 years). Initial pulmonary function, measured between episodes, was worse in patients with allergic aspergillosis than in those without (mean % predicted: FEV1 57% v 83%, vital capacity (VC) 76% v 88%). During a mean follow up period of 12 years neither group displayed further decline in FEV1 or VC. PMID- 2595634 TI - Cardiopulmonary response to oxygen therapy in hypoxaemic chronic airflow obstruction. AB - The acute change in pulmonary artery pressure in response to oxygen may have prognostic value for patients with chronic obstructive pulmonary disease treated with long term domiciliary oxygen. A study was carried out to elucidate the mechanism of the acute cardio-respiratory response to oxygen in such patients and to determine whether it can be quantified non-invasively. The effects of acute oxygen administration (100% for 20 minutes and 28% oxygen for 24 hours) were assessed by non-invasive means and right heart catheterisation in 17 patients with severe stable hypoxaemic chronic obstructive pulmonary disease. Measurements included change in the ratio of dead space to tidal volume (VD/VT), effective pulmonary capillary blood flow (by rebreathing and single breath soluble gas uptake: QRB, QSB), left ventricular ejection fraction (radionuclide ventriculography), and M mode echocardiographic estimates of ventricular diameters and fractional shortening. These values were compared with those obtained from right heart catheter measurements of pulmonary artery pressure, cardiac index (thermodilution and direct carbon dioxide Fick: QTD, QFICK), and pulmonary vascular resistance. Oxygen administration resulted in a significant fall in pulmonary artery pressure, QTD, and QRB and a significant increase in VD/VT. The fall in QRB after 100% oxygen breathing for 20 minutes correlated strongly with the fall in pulmonary artery pressure (r = 0.86). There was no correlation between the fall in pulmonary artery pressure and the fall in QSB or the risen in VD/VT. Left ventricular ejection fraction did not change significantly. Echocardiography was technically unsatisfactory because of lung hyperinflation. Apart from a possible relation between VO2max and fall in pulmonary artery pressure after 24 hours of 28% oxygen breathing (r = 0.49, p less than 0.1) none of the baseline respiratory function measurements predicted the fall in pulmonary artery pressure or QRB. It is concluded that the cardiopulmonary response to acute oxygen breathing in patients with hypoxic chronic obstructive pulmonary disease includes a reduction in pulmonary artery pressure and cardiac output and a redistribution of pulmonary blood flow, and that rebreathing measurements of effective pulmonary blood flow can be used to quantify this response non-invasively. PMID- 2595635 TI - Nutritional state and exercise performance in patients with chronic obstructive lung disease. AB - The relation between exercise performance and certain measures of nutritional state was investigated in 83 patients with stable chronic obstructive lung disease (mean age 62 (8) years). All patients had a forced expiratory volume in one second (FEV1) less than 50% predicted, an arterial oxygen tension of more than 7.3 kPa, and no severe locomotor, cardiovascular, neurological, or endocrine disorders. Exercise performance was assessed from a 12 minute walking test; body weight (as a percentage of ideal weight), creatinine height index, and serum concentrations of albumin, transferrin, and prealbumin were assessed as measures of nutritional state. Mean values of the nutritional variables were within the normal range. The mean (SD) 12 minute walking distance was 686 (254) metres. Walking distance was positively associated with serum albumin concentration and creatinine height index but not with body weight, serum prealbumin, or serum transferrin concentrations. When patients were categorised into low, medium and high performance groups on the basis of their walking distance, a very low creatinine height index (mean (SD) 59% (19%] was found in the low performance group. Albumin explained part of the variance in walking distance independently of pulmonary function in a stepwise regression analysis. The findings suggest that in patients with chronic airflow obstruction skeletal muscle mass and serum albumin concentration are positively associated with exercise performance as measured with a 12 minute walk. PMID- 2595636 TI - Effect of nebulised salbutamol on maximal exercise performance in men with mild asthma. AB - The effect of 5 mg nebulised salbutamol on the cardiorespiratory responses to a progressive maximal exercise test was investigated in eight asthmatic (mean forced expiratory volume in one second (FEV1) 3.48 (1.0) litres) and eight non asthmatic men. Exercise tests were performed on a bicycle ergometer after administration of nebulised salbutamol or matched saline placebo. In the asthmatic subjects salbutamol increased the resting FEV1 by 11%. The mean (SD) percentage fall in FEV1 after exercise did not change significantly (salbutamol 9.4 (12.8); placebo 15.0 (8.0], but because the FEV1 before exercise was increased the lowest FEV1 after exercise was also significantly higher after salbutamol than placebo (3.60 (1.13) v 2.85 (0.80) litres). Despite the improvement in FEV1 before exercise there was no significant difference in maximal workload, oxygen uptake, heart rate, or ventilation during exercise after salbutamol compared with placebo in the asthmatic patients. Tidal volume was higher at maximal exercise after salbutamol but there was no change in perception of breathlessness or exertion in the asthmatic subjects. During submaximal progressive exercise the perceived rate of exertion was reduced in the asthmatic patients and oxygen pulse was reduced in both groups owing to a small and non significant increase in heart rate. The FEV1 and cardiorespiratory response to the progressive maximal exercise test in the non-asthmatic subjects were otherwise unchanged after salbutamol. The results suggest that 5 mg nebulised salbutamol has little effect on the cardiorespiratory responses to progressive maximal exercise in patients with mild asthma and in non-asthmatic subjects. Salbutamol in this dose may reduce the severity of exercise induced asthma, but no ergogenic effect on maximal exercise performance was shown. PMID- 2595637 TI - Prevalence of asthma, atopy, and bronchial hyperreactivity in bronchiectasis: a controlled study. AB - The prevalence of atopic diseases and bronchial reactivity to histamine and methacholine was determined in 36 patients with bronchiectasis and in 36 control patients matched for age, sex, and smoking history. There was no difference in the prevalence of asthma, other atopic diseases, family history of atopic diseases, or positive responses to skinprick tests (nine versus five) in the two groups. The prevalence of bronchial hyperreactivity, however, was significantly higher in the group with bronchiectasis than in the control group for both histamine (7 v 0 patients) and methacholine (6 v 0 patients). The group with bronchiectasis had more airflow obstruction (mean FEV1 67% predicted), but there was no correlation between spirometric indices and log PD20 (the log dose of histamine or methacholine causing a 20% fall in FEV1). This suggests that, although reduced airway calibre may be a factor underlying bronchial hyperreactivity in bronchiectasis, it is not the only mechanism. Further studies are needed to determine whether bronchial hyperreactivity has a causative role in the pathogenesis of bronchiectasis or whether it occurs as a result of the disease. PMID- 2595638 TI - Generalised non-reactive tuberculosis: a clinicopathological study of four patients. AB - Non-reactive tuberculosis is a histopathological entity characterised by foci of necrosis surrounded by normal parenchyma and absence of epithelioid cell granulomas. The clinical presentation and necropsy findings in four patients are described and the pathogenesis of the disease discussed. PMID- 2595639 TI - Transbronchial biopsy without fluoroscopy: a five year experience in outpatients. AB - Transbronchial biopsy is the technique of choice for obtaining tissue for histological diagnosis in many pulmonary disorders. The procedure has usually been carried out as an inpatient procedure with the use of fluoroscopy, though this policy has recently been questioned. This report concerns a five year experience of 174 transbronchial biopsies performed without fluoroscopy as an outpatient procedure in patients with interstitial lung disease or a suspicion of sarcoidosis. Chest radiography was carried out only if the patient developed symptoms. No major complications were encountered and the overall complication rate was low. Pneumothorax occurred in six patients (3.4%), only one of whom required intercostal intubation, and bleeding of more than 30 ml occurred in two patients. Histological diagnosis was obtained in 154 patients (88%). In the experience of this group transbronchial biopsy has been safe when carried out as an outpatient procedure without fluoroscopic guidance. PMID- 2595640 TI - Cystic lung in Marfan's syndrome. AB - Various pulmonary problems have been described in Marfan's syndrome. Unusual cystic lung changes in a young girl with Marfan's syndrome are described. PMID- 2595641 TI - Tracheal lipoma. AB - A 50 year old man was found to have a tracheal lipoma two years after first noticing symptoms. PMID- 2595642 TI - [Pharmacokinetics of sulindac in aged patients presenting with inflammatory joint disease]. AB - The kinetic of sulindac and its two metabolites (sulfide and sulfone) was investigated in twelve elderly patients, following multiple oral dose administration of 400 mg/d. Data were compared to those obtained previously in ten healthy volunteers who received the same dosage regimen. Following multiple dose administration, accumulation ratios indicate that sulindac do not accumulate either in elderly patients (R = 1.35; R = AUC0-24 J8/AUC0-24 J1) or in healthy young subjects (R = 1.38; R = U0-24 J1). No significant modification of sulindac and sulfide kinetic parameters was observed. The apparent bioavailability of the inactive metabolite, sulfone, was found to be doubled in elderly patients (p less than 0.05). We conclude that there is no need to modify the dosage regimen of Arthrocine (400 mg once a day) in elderly patients. PMID- 2595644 TI - [Absence of an anti-ischemic effect of the peripheral benzodiazepine receptor antagonist PK 11195. Study by atrial stimulation in man]. AB - We investigated the anti-ischemic effects of PK 11195 (RP 52028), a selective ligand for peripheral type benzodiazepine binding sites in man. In a first series of patients, we did not find any hemodynamic effect of 10 mg (8 patients) or 20 mg (8 patients) of the intravenously administered drug. The anti-ischemic effect was evaluated on 16 patients with coronary heart disease and a positive stress test in a double blind study of 20 mg of intra-venous PK 11195 (8 patients) versus placebo (8 patients). Ischemia was induced by pacing, and assessed by ST segment depression and lactates extraction before and 15 minutes after administration of the drug. No statistical differences could be found on these ischemia indices between the placebo and PK 11195 treated groups. Although experimental studies have shown interaction of the drug with the calcium channels, our study did not demonstrate any anti-ischemic effect with the dosage used. PMID- 2595643 TI - [Effects of 3 doses of maprotiline (25, 50 and 75 mg) on alertness and memory in healthy volunteers]. AB - The effects on psychomotor and mnesic performance of acute oral doses of maprotiline (25, 50 and 75 mg) were evaluated in twelve healthy men in a placebo controlled double blind study. A battery of tests was performed comprising: objective measures (critical flicker frequency, choice reaction time, memory tasks) and self rating evaluation (visual analogue scales). Tests session took place 15 hours after each treatment. Plasma concentrations of maprotiline were determined. Compared with placebo, maprotiline induced psychomotor impairment on both objective and subjective assessment in a dose related manner. No significant difference between maprotiline and placebo on memory test could be evidenced. PMID- 2595645 TI - [Proteinuria after infusion of gelatin. Comparison of Plasmion and Haemaccel]. AB - Modified gelatin are said without deleterious effect on kidney, an important proteinuria as been seen however in surgical patients after gelatin perfusion. A study in 15 patients scheduled for abdominal surgery compared the renal effects of two modified gelatin: Plasmion (gr P) and Haemaccel (gr H) administered in a similar manner. In the two groups proteinuria appears as soon as perfusion begins with at the third hour a peak which may be as high as 6 g/l. In the same time low molecular weight proteinuria (less than 30 kdalton) appears. The beta 2 microglobulinuria (beta 2m) is significatively enhanced (p less than 0,001). Albuminuria is also enhanced but without statistic signification. Comparison between the two groups reveals that in gr P proteinuria is of the same importance, but delayed, with a significatively smaller elimination of beta 2m (1,8 mg/mmol creatininuria versus 8,6,p less than 0,001). Enzymuria increases in a variable fashion. Proteinuria is probably due to tubular reabsorption inhibition of filtered protein induced by gelatin, particularly by amino acids arginine and lysin which become free after gelatin hydrolysis. If this phenomenon is pathologic or not is unclear and gelatin cannot be said absolutely innocuous. However this phenomenon must be known when proteinuria specially beta 2m is to be interpreted. PMID- 2595646 TI - [Slow-release verapamil 240 mg and treatment of mild to moderate hypertension]. AB - The study was carried out in association with medical practitioners who were responsible for observing the patients. Its aim was to determine the effective dosage of slow release verapamil (V) in the treatment of mild to moderate hypertension and to compare plasma concentrations of V with blood pressure effects. The study comprised a 2-week placebo period and a 3-month active treatment period with V, during which patients were examined, 20-24 h after last intake of V, at the end of the first (D30) and of the third (D90) month of treatment. Active treatment started with 240 mg of V (once a day); at D-30 if diastolic blood pressure (DBP) remained above 90 mmHg the dosage of V was increased to 480 mg (t.d.s.). At each examination blood pressure, body weight and heart rate were registered, electrocardiogram and routine biochemical tests were carried out; plasma concentration of V was measured at D30 for every patient and at D90 for those receiving 480 mg. of V. Thirty patients (11 men and 19 women) aged from 29 to 80 years (mean : 61.7) took part in the study. Treatment needed to be stopped in one patient; results are based on the other 29. At D30 systolic blood pressure (SBP) fell from 179.4 +/- 5.9 to 156.2 +/- 5,5 mmHg and DBP from 101.3 +/- 1.8 to 88.3 +/- 3 mmHg; DPB became normal (less than 90 mmHg) in 23 subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2595647 TI - [Influence of surgical biliary pathology on the diffusion of ceftriaxone in the biliary tract]. AB - Ceftriaxone is a third generation cephalosporin remarkable for its wide distribution in the biliary tract. The purpose of this study was to determine whether biliary tract pathology, as observed during surgery, had an influence on this distribution. 52 patients about to be operated upon and presenting with a high risk of bile infection received a single 1 or 2 g dose of ceftriaxone administered intravenously over 20 min during the hour that preceded surgery. Samples of blood and of bile from the gallbladder (GB) and the common bile duct (CBD), as well as specimens of the GB wall were taken during the operation. In patients whose GB was normal at laparotomy (apart from stones) ceftriaxone concentrations in bile and GB wall were 10-25 and 2 times respectively higher than in plasma. In patients with a grossly distended but not infected GB (hydrocholecystis) ceftriaxone levels were high in CBD bile but null in GB bile and only one-quarter to one-half of plasma levels in GB wall. In patients with stones in the CBD or inflamed GB wall ceftriaxone levels were high in bile (although lower than in cases with normal GB) and similar to plasma levels in GB wall. When malignant pancreatic lesions were present ceftriaxone concentrations could not be measured in both GB and CBD bile but reached 50% of plasma concentrations in GB wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2595649 TI - The alpha-2 adrenoceptor antagonist yohimbine does not facilitate weight loss but blocks adrenaline induced platelet aggregation in obese subjects. PMID- 2595650 TI - [Manifestations of Hodgkin's disease caused by retinoids?]. PMID- 2595648 TI - [Limitations of normal eosinophilia or possible influence of nonsteroidal anti inflammatory agents]. AB - Statistical analysis of eosinophilia of 331 patients at the onset of hospitalisation define a logarithmic standard population of 327 patients whose eosinophilia rates stand between 0 and 810/mm3, among them 24 lies between 500 and 810, and 4 whose eosinophilia rise over 1,000/mm3. These 4 patients had transient hypereosinophilia whose etiology was defined only in 2 cases. The 24 patients with eosinophilia between 500 and 810/mm3 were significantly more frequently men, with rheumatoid disease (specially sciatica) and users of non steroidal antiinflammatory drugs (NSAID) than the general population. It suggest that NSAID may rise eosinophilia rates inside normal limits. PMID- 2595651 TI - [Major eosinophilia during treatment with trimethoprim-sulfamethoxazole]. PMID- 2595652 TI - [Biological evaluation of the microbial respiratory vaccine MRV in children with recurrent bronchitis]. PMID- 2595653 TI - XIIth congress of the International Society on Thrombosis and Haemostasis. Tokyo, Japan, 19-25 August 1989. Abstracts. PMID- 2595654 TI - Rat platelets adhere to human thrombin-treated rat lungs under flow conditions. AB - Platelet attachment to thrombin-treated endothelium was examined under flow conditions in the vascular bed of isolated perfused rat lungs. The infused thrombin bound to the pulmonary endothelium in a specific, competitive manner as shown by displacement of 125I-alpha-thrombin with an excess of cold diisopropylfluoro-phosphate-alpha-thrombin. alpha-Thrombin significantly increased the attachment of isolated 51Cr-labelled rat platelets to the perfused lungs. Scanning and high voltage electron microscopy showed single platelets in various stages of activation attached to pulmonary endothelium. The receptor binding site and catalytic activity of thrombin were essential to the enhancement of platelet attachment. Aspirin given to rats before the lung isolation had no effect on thrombin-induced platelet attachment. Thus, endothelial bound thrombin initiates platelet activation and enhances subsequent platelet attachment. PMID- 2595655 TI - Adhesion of polymorphonuclear leukocytes to protein-coated and platelet adherent surfaces. AB - Since protein adsorption and platelet adhesion are likely to precede significant contact of leukocytes with the surfaces of artificial organs, we have chosen to study polymorphonuclear leukocyte (PMN) adhesion in a sequential manner. The work presented here deals with the effects of flow and surface type on PMN adhesion to fibrinogen- and albumin-coated glass. We compared direct adhesion to adsorbed protein with adhesion to adsorbed protein having adherent platelets. These experiments were designed to see if PMN's might preferentially adhere to albumin or fibrinogen and whether a particular morphological form of adherent platelet could promote PMN adhesion. The adhesion of PMN's to spread platelets on albumin or fibrinogen occurs to a greater extent than in the absence of platelets. Adhesion of PMN's to spread platelets may be an important mechanism for their depletion from the circulation during artificial organ use. PMID- 2595656 TI - Procoagulant activity of endocardial vegetations and blood monocytes in rabbits with Streptococcus sanguis endocarditis. AB - To investigate activation of the coagulation system in bacterial endocarditis, we determined the procoagulant activity of blood monocytes isolated from rabbits with Streptococcus sanguis-infected or sterile catheter-induced endocardial vegetations. This activity was determined directly after isolation from the peripheral blood and after stimulation in vitro by either endotoxin or by phagocytosis of S. sanguis. The procoagulant activity of the vegetations of these rabbits was also determined. The procoagulant activity of blood monocytes of rabbits with S. sanguis endocarditis was found to be similar to the activity of monocytes of rabbits with sterile vegetations, both at the time of isolation and after stimulation in vitro by exposure to endotoxin or phagocytosis of bacteria. The procoagulant activity of infected vegetations was significantly higher than that of sterile vegetations. We conclude that in bacterial endocarditis the coagulation system is activated locally at the site of the vegetation. Triggering probably occurs by thromboplastin generated by monocytes activated by phagocytosis of bacteria on the vegetational surface. PMID- 2595657 TI - An evaluation of impedance plethysmography and 125I-fibrinogen leg scanning in patients following hip surgery. AB - Venous thromboembolism is a common post-operative complication in patients following hip surgery. 125I-fibrinogen leg scanning and impedance plethysmography (IPG), are often used in the detection of venous thrombi in such patients. Information on the sensitivity and specificity of these non-invasive tests for the diagnosis of venous thrombosis following hip surgery is relevant for both patient management and for choosing the appropriate outcome measure for clinical trials evaluating new prophylactic regimens. We determined the sensitivity and specificity of the IPG alone, the 125I-fibrinogen leg scan alone, as well as the combined use of the two tests from a retrospective analysis of 685 hip surgery patients who participated in clinical trials of anti-thrombotic prophylaxis. These patients were followed prospectively with non-invasive tests. Bilateral venography was attempted either when one or both screening tests became positive or on day 10-14 post-operatively if both screening tests remained negative. Adequate venography was obtained in 1,010 (73.7%) legs and thrombi were identified in 198 (19.6%) legs. The sensitivities of the IPG and leg scanning were 12.9% and 44.6% respectively; the corresponding specificities were 98.1% and 95.0%. The sensitivity of a positive result on one or both screening tests was 49.6% with a specificity of 93.9%. Therefore, leg scanning and IPG, even in combination, are not sufficiently accurate to be recommended as the only strategy for the diagnosis of venous thrombosis following hip surgery. Venography should be considered in all patients undergoing surveillance testing either when one or both of the screening tests become positive or on day 10-14 if the screening tests remain negative. PMID- 2595658 TI - Arterial thrombosis associated with immune thrombocytopenia: presence of a platelet aggregating IgG synergistic with thrombin and adrenalin. AB - We report the case of a 50-year-old lady who presented with arterial thrombosis in the setting of thrombocytopenia. Investigations confirmed the diagnosis of idiopathic thrombocytopenic purpura. A spontaneous platelet aggregating factor (SPAF) was isolated from the immunoglobulin fraction of the patient's plasma. The isolated IgG irreversibly aggregated platelet-rich plasma and washed platelets, an effect abolished by pretreating the platelets with aspirin. The activity of the IgG was greatly enhanced by subaggregatory concentrations of thrombin and adrenalin and was localized to the F(ab')2 of the molecule. Plasmapheresis in combination with anti-platelet therapy resulted in an increase in the patient's platelet count, reduced platelet aggregating activity of plasma and significant clinical improvement. We suggest that the presence of this platelet aggregating IgG contributed to the development of thrombosis in our patient and postulate that a similar factor may explain the paradox of thrombosis observed in a select group of thrombocytopenic patients. PMID- 2595659 TI - Factors of the extrinsic pathway of blood coagulation in tumour associated macrophages. AB - Despite the growing evidence implicating intratumoural fibrin formation in the progression of malignant tumours, the origin of coagulation factors that participate in extravascular clotting has not been elucidated. Using immunohistochemical methods we attempted to detect and localize clotting factors of extrinsic pathway in different human malignant tumours. Coagulation factors II, V, VII and X (FII, FV, FVII and FX) were detected in a huge number of cells showing spindle-shaped or stellate morphology. By double immunohistochemical labellings it was demonstrated that cells containing these clotting factors express monocyte/macrophage differentiation marker antigens recognized by Leu M3, Ki M7 and DAKO-macrophage monoclonal antibodies, i.e. they represent monocyte derived, phagocytic tumour associated macrophages (TAMs). These findings suggest that TAMs can be viewed as clot cells, which in addition to the initiation of extravascular clotting by expressing procoagulant activity can also provide all the components necessary for the extrinsic thrombin formation. PMID- 2595660 TI - Extrinsic pathway inhibitor in elective surgery: a comparison with other coagulation inhibitors. AB - Extrinsic coagulation pathway inhibitor may be an important regulator of haemostasis to prevent thrombosis after tissue damage. The functional activity of this inhibitor was determined using a chromogenic substrate assay, and compared to the activities of antithrombin, heparin cofactor II and protein C during the perioperative period of elective hip replacement (n = 28), cholecystectomy (n = 11), and vascular surgery (n = 5). Peroperatively, all the inhibitors decreased rather similarly and to the same degree as the decrease in albumin concentration. The decreases during hip surgery were about 2-fold the decreases observed during cholecystectomy. A significant peroperative increase in extrinsic pathway inhibitor activity was observed in vascular surgery, probably due to a bolus injection of heparin. Antithrombin, heparin cofactor II and protein C levels normalized on days 3-5 postoperatively in all three patient groups. Sustained low levels of extrinsic pathway inhibitor were observed on postoperative days 1 to 7 in hip surgery patients. Apparently, extrinsic pathway inhibitor is not an acute phase reactant. In uncomplicated surgery, the decreases of the coagulation inhibitor levels are mainly due to hemodilution. PMID- 2595661 TI - The effect of some instruments for prothrombin time testing on the International Sensitivity Index (ISI) of two rabbit tissue thromboplastin reagents. AB - Two commercial rabbit tissue thromboplastins were calibrated against the International Reference Preparation for rabbit thromboplastin (coded RBT/79) by one laboratory using the manual technique, a semi-automatic electro-mechanical coagulometer and three different automatic photo-optical instruments. The calibration of the two reagents was performed in three and two different exercises, respectively, and showed good reproducibility of the procedure. The purpose of calibration is providing a formula for the assessment of the International Normalized Ratio (INR) for patients receiving oral anticoagulants. The World Health Organization (WHO) model for thromboplastin calibration leads to the equation INR = RISI, in which R is the prothrombin time ratio and ISI the International Sensitivity Index of the calibrated thromboplastin/instrument system. This equation was adequate for one reagent, but not for the other when it was used in combination with the four instruments. At therapeutic intensities of anticoagulation, the deviation from the WHO-model observed for the second reagent was clinically insignificant. The WHO model was fully adequate when the second reagent was used with the manual technique. For both thromboplastins, there were statistically significant differences in ISI between the four instruments. The largest difference--amounting to approximately 10%--was observed between two photo-optical instruments. The order of instruments with increasing ISI was the same for the two reagents. It is recommended that thromboplastin manufacturers specify the instruments used for calibration of their reagent. PMID- 2595662 TI - Procoagulant activity of T lymphoblastoid cells in extrinsic and intrinsic coagulation systems. AB - We have measured the procoagulant activity (PCA) of four T lymphoblastoid cell lines (Jurkat, CEM, HSB-2 and Molt 4) as well as normal peripheral blood T lymphocytes, before and after stimulation with phytohaemagglutinin (PHA), using clotting and amidolytic methods. Of the four cell lines only one, Jurkat, gave enhanced PCA after stimulation with PHA. This activity was shown to be tissue factor-like by its dependence on factor VII in plasma and in an amidolytic assay with purified factors VII and X. Jurkat was also the only one of the four cell lines to secrete interleukin-2. All four cell lines promoted the generation of large amounts of thrombin in platelet-free plasma in glass tubes. This activity was dependent on the presence of plasma factor VIII, and was probably due to phospholipids in the cell membranes. Normal T lymphocytes gave intrinsic PCA in the thrombin generation test which was only 15% of that of the lymphoma cells. These results show that some T lymphocytes can develop PCA in both intrinsic and extrinsic systems and this should be taken into account in studies of the PCA of mixed leukocyte populations. PMID- 2595663 TI - Molecular forms of human protein C: comparison and distribution in human adult plasma. AB - Protein C (PC) is a vitamin K-dependent protein which functions as both an anticoagulant and profibrinolytic. It is synthesized as a single chain protein (SC-PC) and post-translationally modified into a two chain form (2C-PC). Two chain PC consists of a light chain (LC) and a heavy chain (HC). The present study was undertaken to determine the composition of the molecular forms of PC in plasma. PC was immunoprecipitated, subjected to SDS-PAGE and Western blotting. The blots were scanned by densitometry to determine the distribution of the various forms. The percentage of SC-PC and 2C-PC was found to be 10% and 90% respectively. This is in agreement with previous work. SC-PC and the heavy chain of 2C-PC consisted of three molecular forms ("alpha", "beta", and "gamma"). The "alpha" form of HC is the standard 2C form with a MW of 40 Kd. The "beta" form of HC has also been described and has MW which is 4 Kd less than the "alpha" form. The "gamma" species of the SC and 2C-PC has not been previously described. However, its 3 Kd difference from the "beta" form could be due to modification of the "beta" species or to a separate modification of the alpha-HC. The LC of PC was shown to exist in two forms (termed form 1 and form 2). The difference between these two forms is unknown. The molecular forms of PC are most likely due to a post-translational modification (either loss of a carbohydrate or a peptide) rather than from plasma derived degradation. PMID- 2595665 TI - The absorption, clearance and metabolic fate of dermatan sulphate administered to man--studies using a radioiodinated derivative. AB - An iodinated derivative of dermatan sulphate was administered by the intravenous, subcutaneous and oral routes to healthy human volunteers in conjunction with unlabelled dermatan sulphate. Following intravenous injection clearance of radiolabel and concentration as measured by competitive binding assay were highly correlated and displayed complex kinetics which were not dose-dependent. Intact 125I-dermatan sulphate was absorbed following both subcutaneous and oral administration, though there appeared to be selective uptake by the gut of a subfraction comprising the smaller or less sulphated molecules. The intact material was subsequently excreted unchanged in the urine. Degradation products of dermatan sulphate were not detected by either gel filtration or affinity chromatography on Polybrene-Sepharose at any time in either plasma or urine, indicating that administered dermatan sulphate is not catabolised by man. PMID- 2595664 TI - The incidence and clinical significance of amiodarone and acenocoumarol interaction. AB - Acenocoumarol sensitivity index (ASI) was calculated in 36 patients receiving amiodarone and acenocoumarol concomitantly, by dividing the acenocoumarol daily dose (micrograms kg-1 day-1) by the prothrombin ratio expressed as International Normalised Ratio (INR). It was found to be significantly lower (4.2 +/- 0.3 micrograms kg-1 day-1) than the ASI (11 +/- 0.6 micrograms kg-1 day-1) determined in 35 patients in the control group, who received acenocoumarol and not amiodarone. In 15 patients, ASI was 13.2 +/- 1.4 and 4.2 +/- 0.6 micrograms kg-1 day-1 before and after initiation of amiodarone therapy, respectively. In 5 patients, ASI was 6.2 +/- 0.6 micrograms kg-1 day-1, while patients were receiving both medications, and 28.1 +/- 6.1 micrograms kg-1 day-1 following discontinuation of amiodarone therapy. ASI determined while patients were on both medications was not affected by the presence of mild impaired renal or liver function. In 7 patients treated with both drugs concomitantly, severe bleeding diathesis developed. It is concluded that amiodarone augmented the anticoagulant effect of acenocoumarol in all patients receiving both drugs. An initial reduction of acenocoumarol daily dose by 50% and further adjustment of acenocoumarol dose according to daily prothrombin ratio is recommended. It is also suggested that acenocoumarol dose should be adjusted after cessation of amiodarone therapy. PMID- 2595667 TI - Mechanism of potentiation by manganese ion of aggregation of porcine pancreatic elastase-treated human platelets. AB - The effect of manganese ion (Mn2+) on the aggregation of porcine pancreatic elastase-treated platelets (ETP) induced by fibrinogen (Fbg) was studied. Mn2+ enhanced the aggregation of ETP on addition of Fbg specifically and dose dependently. This effect of Mn2+ was not associated with the formation of thromboxane A2, and was not affected by pretreatment of ETP with acetylsalicylic acid in the presence of Mn2+. Moreover, it was not dependent on extracellular adenosine diphosphate, as shown by removal of extracellular adenosine diphosphate by pretreatment of ETP with creatine phosphate/creatine phosphokinase. Studies on the binding of 125I-Fbg to ETP showed that Mn2+ increased the Kd value of binding but did not affect the number of Fbg binding sites. These results indicate that Mn2+ specifically and dose-dependently potentiated Fbg-induced aggregation of ETP and that this effect of Mn2+ may be due to an increase in the affinity of binding of Fbg to the glycoprotein IIb-IIIa complex on the membranes of ETP. PMID- 2595666 TI - Aggregation to thrombin and collagen of platelets from a Glanzmann thrombasthenic patient lacking glycoproteins IIb and IIIa. AB - The aim of this study was to investigate the platelets of a Glanzmann thrombasthenic patient, which in citrated PRP failed to respond to various agonists, but aggregated and secreted to high concentrations of thrombin (0.36, 0.72 and 1 U/ml) and collagen (4, 10 and 20 micrograms/ml) when washed and resuspended in a Tyrode-albumin solution (containing 2 mM Ca2+). Aggregation of the patient platelets was not affected by anti-IIb/IIIa monoclonal antibody (P18) which strongly inhibits thrombin or collagen induced aggregation of normal platelets. Washed platelets of this patient did not aggregate to ADP (10-100 microM) in the presence of added fibrinogen (2 mg/ml) nor bind 125I-labelled fibrinogen (40 to 320 micrograms/ml) when thrombin-stimulated. Different anti IIb/IIIa monoclonal antibodies (P2, P18) when used in binding or crossed immunoelectrophoretic studies showed a complete absence of the IIb-IIIa glycoprotein complex on the patient platelets. Moreover, glycoproteins IIb or IIIa were absent on silver-stained two-dimensional (non-reduced/reduced) polyacrylamide gel separations of the patient platelets and were not detected by Western blots used in combination with anti-PLA1 (antigen present on IIIa), anti Leka (antigen present on IIb). This study shows that platelets lacking glycoproteins IIb or IIIa can aggregate in response to high concentrations of collagen or thrombin when resuspended in the presence of physiological concentrations of calcium. Results obtained in this study could indicate the existence of other mechanisms (other than the IIb-IIIa glycoprotein complex) involving glycolipids, heparans, proteoglycans, and/or unknown membrane glycoproteins to mediate platelet aggregation of stimulated thrombasthenic platelets. PMID- 2595668 TI - Structural and immunological properties of myosin from human platelet external and internal membranes. AB - Our previous studies indicate that platelets contain two myosin isoforms, one of them localized in the membrane while the other in the cytoplasmic compartment. Structural and functional differences of these myosins have been characterized. In this study two platelet membrane subfractions, the external and the internal membranes, were isolated simultaneously from a crude membrane fraction and their purity was characterized using specific marker enzymes. Myosin was shown to be present in both membrane fractions and its structural and immunological properties were investigated. The electrophoretic mobilities of myosin in both membrane preparations were identical to the mobility of its cytoplasmic counterpart. Two-dimensional peptide mapping of the iodinated tryptic peptides of the myosin heavy chains indicated that at least one peptide is missing in the maps of the myosins from the external and internal membranes as compared to their soluble counterpart. Our data suggest that myosin is located in three distinct platelet compartments: cytosol, external and internal membranes. The same myosin isoform is located in the two membrane compartments, while the isoform found in the cytosol is different. The observed variations in the structure of the two isoforms may reflect differences in their respective physiological functions. PMID- 2595669 TI - Purification and characterization of rabbit tissue factor. AB - Anti-human tissue factor IgG column was used to partially purify rabbit tissue factor. The rabbit tissue factor was then further purified on SDS-polyacrylamide gel electrophoresis to prepare an essentially homogeneous rabbit tissue factor. This was used as an antigen to raise a high titer, monospecific, polyclonal antiserum for rabbit tissue factor. Immunostaining of a crude Triton extract of rabbit brain acetone powder and purified tissue factor with the anti-rabbit tissue factor IgG yielded a single major band with an apparent molecular weight of 45 kD, which corresponds to the mobility on SDS-PAGE of purified rabbit tissue factor apoprotein. The anti-rabbit tissue factor IgG was coupled to Affi-Gel-15 and used as an immunoadsorbent column to purify large amounts of rabbit brain tissue factor in a rapid, one-step technique. PMID- 2595670 TI - New heparin complexes active by intestinal absorption: I-multiple ion pairs with basic organic compounds. PMID- 2595671 TI - Hormonal regulation on bioactive aortic substance (BAS) production. AB - Rat's vessel wall releases a protein named BAS (Bioactive Aortic Substance) whose antiaggregating effect on platelets and inotropy vascular properties have been already described. In this work we have investigated the effects of pregnancy, gonadectomy and gonadectomy with hormonal treatment on the BAS production from rat aortic rings. BAS production in pregnancy and ovariectomized rats was markedly decreased compared to normal rats. Return to normal values was obtained after estradiol treatment in ovariectomized rats. Castration resulted in an increased of BAS production which was suppressed by testosterone treatment. PMID- 2595672 TI - Effect of acenocoumarine on the breast-fed infant. AB - Apart from teratogenic phenomena and the potential risk of maternal or neonatal peripartum haemorrhage, the use of oral anticoagulants during pregnancy poses an additional hazard: the risk of transferring some anticoagulant activity to the nursing infant through breast milk. We analysed the coagulation status of seven full term breast-fed neonates whose mothers were under chronic anticoagulant therapy with acenocoumarine as thromboembolic prophylaxis following cardiac valve replacement. Prothrombin Times (PT) observed in neonates were significantly higher than the corresponding maternal values. Data were subsequently compared with those obtained from a control group comprising forty-two full term neonates nursed by non-anticoagulated mothers: coagulation profiles again showed no signs of any noticeable antivitamin K effect. Our results indicate that mothers given acenocoumarine at therapeutic doses may safely breast-feed their infants: anticoagulant activity in breast milk seems to be negligible as assessed by neonates PT. PMID- 2595673 TI - Accumulation of 125I-factor XI in atheroma of rabbit with hereditary hyperlipidemia (WHHL-rabbit). AB - We have studied the turnover and accumulation of rabbit factor XI (F.XI) in atherosclerotic lesion in Watanabe-hereditable hyperlipidemic rabbit (WHHL rabbit) to reveal the participation of blood coagulation in atherosclerotic lesion. Rabbit F.XI was iodinated and administered intravenously to WHHL rabbits and Japanese white rabbits. The turnover of 125I-rabbit F.XI was significantly faster in WHHL rabbits (T1/2 = 2.84 +/- 0.44 days) than in normal rabbits (T1/2 = 4.44 +/- 0.42 days). The thoracic aorta of WHHL rabbit was strongly labelled with 125I-rabbit F.XI, in sections obtained after 5 days by en-face autoradiography, whereas no radioactivity was detected in normal aorta. By an immunohistochemical study of WHHL rabbit aorta, we confirmed that many F.XI- and fibrin-related compounds existed in the atheroma, whereas albumin did not in these area. These results suggest that the activation of F.XI proceeds on the atherosclerotic lesions of WHHL rabbits. PMID- 2595675 TI - Neonatal protein C: molecular composition and distribution in normal term infants. AB - Protein C (PC) is a vitamin K-dependent serine protease which functions as the central regulatory protein with both anticoagulant and profibrinolytic properties. The PC levels in healthy term newborns are approximately one third of adult levels. Severely decreased levels of PC are seen in sick term and preterm infants. These neonates appear to have an increased incidence of thrombosis. Undetectable levels of PC are found in homozygous PC deficient infants with DIC and purpura fulminans symptoms. In this present study we report the composition and distribution of PC in term newborn and compare the results with adult values. Plasma was obtained from placental cord blood of 20 healthy term (38-42 weeks gestation) infants. PC was immunopurified, run on SDS-PAGE, and immuno-blotted. The composition of the PC molecule in neonatal plasma is identical to that seen in adults. Using densitometry to determine the distribution of the PC components, we observed a 2-fold increase in single chain PC in the neonate as compared to the adult. In the neonate, there was an inverse correlation between the level of total PC antigen and the amount of single chain. These findings suggest the possibility that the processing of PC may be developmentally influenced. PMID- 2595674 TI - The interaction of thrombin with platelet protease nexin. AB - Thrombin interacts with a platelet protein which is immunologically related to fibroblast protease nexin and has been termed platelet protease nexin I (PNI). Conflicting hypotheses about the relationship of the thrombin-PNI complex formation to platelet activation have been proposed. The studies presented here demonstrate that the platelet-associated and supernatant complexes with added 125I-thrombin are formed only under conditions which produce platelet activation in normal and chymotrypsin-modified platelets. The platelet-associated complex is formed prior to the appearance of complexes in supernatants. Appearance of the supernatant complex coincides with the appearance of thrombospondin in the reaction supernatants. Excess native thrombin, dansylarginine N-(3-ethyl-1,5 pentanediyl) amide or hirudin can prevent radiolabeled platelet-associated complex formation if added before 125I-thrombin. DAPA or hirudin can prevent or dissociate complex formation if added up to one minute after thrombin but not at later time points. The surface associated complex is accessible to trypsin although a portion remains with the cytoskeletal proteins when thrombin-activated platelets are solubilized with Triton X 100. The surface-associated complex formation parallels many aspects of the specific measurable thrombin binding, yet it does not appear to involve other identified surface glycoprotein thrombin receptors or substrates. Although the time course of appearance of the complexes in supernatants is consistent with other data which suggest that PNI may be released from platelet granules during platelet activation, other explanations for the appearance of PNI on the platelet surface and in supernatants during platelet activation are possible. PMID- 2595676 TI - [Can research be counted?]. PMID- 2595677 TI - [Consolidation and expansion of the Medical Birth Registry]. PMID- 2595678 TI - [Centralized treatment of extensive burns in Norway]. AB - About 800 patients are admitted annually to Norwegian hospitals for burn injuries. Among these, about 5% (40) patients have extensive burns, and 80-110 have special burns (skinburns combined with inhalation injuries, burns of the hands and burns of the face). The National Burn Center at Haukeland Hospital was opened in October 1984. In our experience decreased mortality, reduced disability and quicker rehabilitation are achieved when extensive and special burns are treated in specialized burn units. PMID- 2595679 TI - [Surgical treatment of burns]. AB - At the National Burn Center at Haukeland Hospital, early excision and split skin grafting is a standard method for the treatment of extensive burns. In these cases it is important to be aggressive in the surgical treatment in order to avoid sepsis, multi-organic failure and death. PMID- 2595680 TI - [Physical therapy of extensive burns]. AB - Prevention of contractures is the main goal of the physiotherapist in the treatment of large burns in the acute phase. Prevention of contractures is achieved by positioning, splints, exercises and compression. It is important for the rehabilitation of the patient that the directions from the Burn Unit concerning the treatment of the burn patients are followed up by the local Health Service after discharge. PMID- 2595681 TI - [Psychological problems among children with burn injuries]. AB - Since 1984 children treated in the Department of Burns, Haukeland Hospital, have been evaluated by a child psychiatrist. This article describes the psychological reactions of the children and their parents, and the psychiatric support and treatment provided during the stay in hospital. PMID- 2595682 TI - [Burns among the elderly. Occurrence, causes, local treatment]. AB - Burns in geriatric patients carry a grave prognosis. Reduced thickness of the skin and reduced mobility make older persons susceptible to deep burns. First-aid treatment is insufficient in most instances and generally, there is a delay in seeking medical treatment. Pre-existing degenerative diseases may account for numerous complications and a prolonged course. Accidents at home are most common. It is assumed that most of these could be prevented if proper precautions are taken. Our experiences from treatment of 85 geriatric burn patients at the Red Cross Clinic, Oslo, prompted the present study. We discuss various aspects of problems to geriatric patients. PMID- 2595683 TI - [Risk score for coronary disease. A pedagogic model used in the occupational health services]. AB - In our occupational health service, we have worked out a fairly simple model for risk score for coronary heart disease. The occupational nurses give each employee a risk score after health examination and use this figure as a convincing pedagogic tool in preventive health education. The nurses find a measureable scale extremely useful in the follow-up of groups and individuals. The system is also used to measure the difference in coronary disease risk between different occupations and occupational subgroups. After introduction of this risk score system, both employer and employees seem to be more conscious of health hazards, both in the work environment and due to personal lifestyle. PMID- 2595684 TI - [Disulfiram and acute liver damage]. AB - Few serious side effects have been reported from use of disulfiram. In this article we present a case where therapeutic doses of disulfiram resulted in acute liver damage. We also found neurological symptoms, although such side effects from use of this drug are rare. PMID- 2595685 TI - [The antiphospholipid syndrome]. AB - Coagulopathy leading to arterial and venous thrombosis is sometimes seen in patients with systemic lupus erythematosus (SLE). It is caused by antiphospholipid antibodies reacting with negatively charged phospholipid constituents of membranes and coagulation factors. The patients may also suffer from recurrent fetal loss and neurological manifestations, and may have intermittent thrombocytopenia and low serum concentration of complement factor C4. Patients without evidence of SLE or other immunological disorders may also exhibit this antiphospholipid antibody-associated thrombotic tendency. The patients are often young women, and it is important to be aware of this kind of coagulopathy, because it may take a most severe course in some of the persons affected. PMID- 2595686 TI - [Gene technology in medical microbiology--a general review]. PMID- 2595688 TI - [Status of side effects. 1. Background and current status]. PMID- 2595687 TI - [Gene technology in medical microbiology--epidemiology and diagnosis]. AB - Genetic approaches have been helpful in investigating the epidemiology of infectious diseases. There are many examples in which analysis of plasmid profiles or restriction endonuclease patterns have been used successfully in epidemiological tracing to identify sources of infection and determine the size of an outbreak. A number of genetic probes are presently commercially available to diagnostic microbiological laboratories. Probes have been developed for detection of virulence factors, antibiotic resistance, and for qualitative and quantitative determination of specific pathogens in clinical samples. This technology is currently in the process of being considerably modified and improved, which has already made it an attractive alternative to conventional methods. PMID- 2595689 TI - [Status of side effects. 3. Intensified registration of adverse effects. What should be reported?]. PMID- 2595691 TI - [Ethics and clinical tests]. PMID- 2595690 TI - [Use of citation analysis and other bibliometric methods in evaluation of the quality of research]. AB - Bibliometric methods for scientific evaluation have been critically examined. The citation frequency for scientific publications, as given in the Science Citation Index, is influenced by various forms of citation bias as well as by the characteristic dynamics and citation practices of the various scientific fields, and therefore cannot be taken as an unequivocal measure of scientific quality. Even for single authors the citation frequency is very variable; therefore this parameter should not be used for graded evaluation of individual scientists or research groups. At higher aggregate levels (large institutes etc.) bibliometric indicators may, as part of a more general evaluation, give relevant information about research activity, provided due corrections are made for variable research field effects. The journal impact factor, i.e. the mean citation frequency of all articles in a journal, has been suggested as a rapid indicator of article quality. However, the distribution of citation frequency values within a journal is extremely broad and skewed; therefore, assigning the same value to all articles would not seem to serve the purpose of evaluation particularly well. Furthermore, the citation frequencies of articles published by individual authors or research groups are found to correlate extremely poorly with the corresponding journal impact factors. The latter parameter would thus appear to be unsuitable as an indicator of scientific quality. PMID- 2595692 TI - [A letter from El Salvador]. PMID- 2595694 TI - [Lies about Nutrilett]. PMID- 2595693 TI - [Drinking water for tourists and in the tropics. Purification of drinking water in the field]. PMID- 2595695 TI - [HIV/AIDS epidemics--health education and changes in behavior]. PMID- 2595696 TI - [Anaphylaxis during anesthesia--an increasing problem?]. PMID- 2595697 TI - [Varicose vein surgery]. PMID- 2595698 TI - [Stroke patients--quality of life and economics]. PMID- 2595700 TI - [Stroke patients--a challenge to primary health care]. AB - The aim of this study was to assess the impact of stroke in a community. All new stroke cases in the municipality of Stange were registered during one year. In 10,000 inhabitants we found 48 new cases, 18 of them died during the observation time of six months. 19 patients needed full-time care for 1-4 months, seven of them for more than six months. A general practitioner with 1,500 patients had six new stroke patients a year, four of them needed medical follow-up. To take better care of stroke patients, we need to re-organize and improve the coordination of resources in primary health care. PMID- 2595699 TI - [Being a stroke patient. Psychosocial aspects]. AB - In this article I attempt to throw some light on the psycho-social consequences of stroke. 50% of stroke patients reported depression and/or anxiety. They lost their former interests, and became resigned and passive. There was little connection between psychic well-being and physical function (except in the case of speech difficulties). The relatives of stroke patients felt frustrated over the patients' attitudes, and the lack of help and support from health personnel. PMID- 2595701 TI - [Anaphylactic shock during elective cesarean section. Sensitizing mechanisms and follow-up]. AB - Anaphylactic reactions during anaesthesia are increasing. Women experience these reactions more often than men. In about 50% of the cases the reaction is due to a muscle relaxant drug. Recently, Australian and French researchers have described these reactions as possibly mediated by IgE in most of the patients. As regards Ig-antibody binding, the quaternary ammonium ions seem to be potential determinants in the muscle relaxant molecule. Patients may have been sensitized by exposure to cosmetics, disinfectants or solvents, and cross-reactivity between different neuromuscular blocking agents has been described earlier. We refer to a patient who experienced an anaphylactic shock during anaesthesia by suxamethonium. She was successfully treated with epinephrine, crystalloids and mechanical ventilation. We discuss peroperative treatment, further investigation, and management at later anaesthesiological procedures. PMID- 2595702 TI - [Anaphylactic shock caused by suxamethonium (Curacit)]. AB - We describe five cases of anaphylactic shock following the short-acting muscle relaxant succinylcholine (suxamethonium). All the patients recovered uneventfully. Skin prick testing identified succinylcholine as the probable causative agent in four cases. The incidence of anaphylaxis to succinylcholine in our material appears to be 1:1,000. Treatment consisted of volume substitution, adequate oxygenation and adrenergic agents. We discuss the routine use of succinylcholine for intubation in elective surgery, and conclude that the anaesthesiologist must always be prepared for a possible anaphylactic reaction. PMID- 2595703 TI - [Varices of the great saphenous vein]. AB - During a 7-year period, 237 patients were treated surgically at Tromso Hospital for varices of the great saphenous vein. At follow-up (mean 7.5 years) the overall results were excellent in 30%, good in 47%, and poor in 21% of the patients. The recurrence rate of varicose veins was 47%. However, 50% of these patients had no symptoms or only minor symptoms, from the recurrence. 37 patients noticed the occurrence of troublesome varicose veins within one year after operation. At clinical reexamination it was found that in 32 of these patients the surgery had been inadequate. This probably explains the rapid recurrence. PMID- 2595704 TI - [Treatment of hairy cell leukemia]. AB - Hairy cell leukemia is a rare leukemic variant with a relatively good prognosis. Treatment is indicated when the patient develops symptoms caused by cytopenia. When the spleen is palpable, the primary treatment should be splenectomy. When the spleen is not palpable and/or if the patient relapses after splenectomy, treatment with Alfa-Interferon is indicated. The place of deoxycoformycin in the treatment of hairy cell leukemia has not yet been established. PMID- 2595705 TI - [Infectious complications caused by a hemodialysis catheter. Retrospective study of septicemia related to a dual lumen polyurethane hemodialysis catheter in the subclavian vein]. AB - Of 52 patients started on hemodialysis during two years, 19 used a polyurethane subclavian dual lumen hemodialysis catheter for temporary or permanent vascular access. Three of them (15.8%) got catheter sepsis, and one died. The article discusses prevention of intravascular catheter-related infection, and methods for vascular access. PMID- 2595706 TI - [Use of condoms in relation to risk behavior among the heterosexual population in Norway]. AB - In a questionnaire survey on sexual behaviour, a random sample of 10,000 Norwegians aged 18 through 60 were asked about use of condoms during their last intercourse. The response rate was 62.7%. Except as regards level of education, the response group was fairly representative of the population with respect to socio-demographic variables. About 12% reported use of condom. Among subjects who reported extra-marital partners, about 7% used condoms (both with their permanent and their extra-marital partner), whereas about 12% of subjects who did not have extramarital sex used condoms. 15% of the single persons reported use of condom. Apparently, the use of condoms is not related to sexual behaviour correlated with risk of HIV-infection, such as the number of partners and knowledge about the partner. Neither is perceived risk, as measured by HIV-testing behaviour, related to the use of condoms. PMID- 2595707 TI - [The syringe dispenser project in Larvik. Experiences after one year]. AB - Limiting the use of contaminated syringes is an important step in the battle against hepatitis B and HIV epidemics. In 1987 a project, the first of its kind, was started in Larvik and the county of Vestfold in Norway. Syringe dispensers were put up in order to ensure that drug addicts had access to sterile syringes throughout the day and night. Looking back on one year's operation, the results and reactions are positive. The programme led to increased availability of syringes, reduced use of contaminated syringes, no pollution problems of significance and a decrease in the incidence of hepatitis B. We have also been able to channel increased information to a group hitherto difficult to reach. The involvement of the local public-health authorities has increased their contact with intravenous drug users. This has in turn laid the foundation for better future cooperation with this group. Setting up syringe dispensers has been shown to be an important factor in the battle against hepatitis B and HIV epidemics. This project has also provided a starting point for further work on drug abuse. PMID- 2595708 TI - [Chronic disease and sexuality. An interview study on sexual dysfunction in patients with multiple sclerosis]. AB - Many patients with a chronic disease experience that this condition in some way influences their sexual life. In this paper we present the results from an interview survey of ten patients with multiple sclerosis. The aim of the survey was to assess sexual dysfunctions in patients with chronic disease, the patients' opinion about these matters, and the role of the health services. We found the extent of the sexual problems of these patients to be comparable with the findings presented in earlier studies. The majority of patients considered it a problem that the topic was never raised by their medical practitioner. The patients clearly indicate that it is important for them that this subject be discussed, and that they receive counselling. This task should predominantly be the responsibility of the general practitioner, since she/he is normally the one who ensures continuity in the care of the patients. PMID- 2595709 TI - [The cheapest synonymous preparations--a proposal with unwanted consequences]. PMID- 2595710 TI - [Drug therapy in intermittent claudication]. PMID- 2595711 TI - [The general practitioner: does he hinder or advance medical research?]. PMID- 2595712 TI - [Geriatric rehabilitation]. PMID- 2595713 TI - [Administration of laughing gas during labor may cause later amphetamine addiction in the offspring]. PMID- 2595714 TI - [Caseous lymphadenitis in moorland sheep in The Netherlands]. AB - Caseous lymphadenitis was detected in two flocks of moorland sheep originating from Western Germany. Retrospective serological examination showed that the nucleus flock was infected as early as the time of importation in 1984. PMID- 2595715 TI - [Preliminary experience with a buffy coat analyser in horses]. AB - The present author's practice was offered the opportunity of testing a so-called buffy-coat analyser of the firm of Becton & Dickinson for its use in the field. He does not deny readers the report of his preliminary experience. In addition, the interpretation of the results and the limitations of the apparatus are briefly discussed. PMID- 2595716 TI - [AIDS in cows?]. PMID- 2595717 TI - [Results of a study of the functioning of a veterinary medicine practice]. PMID- 2595718 TI - [Veterinary Chief Inspection for Public Health. Lead poisoning in cattle caused by feed concentrates]. PMID- 2595719 TI - [Brucella abortus]. PMID- 2595720 TI - [Campylobacter jejuni]. PMID- 2595721 TI - Time-dependent variation of HLA-antigen-frequencies in HIV-1-infection (1983 1988). AB - In a 5-year-study of HLA-phenotypes in 411 HIV-1-infected individuals, a progressive decrease of the formerly elevated frequency of HLA-DR5 has been observed. HLA-DR3 seems to have a protective effect. These results are discussed with respect to the mimicry-hypothesis of HLA and disease associations. Further preliminary results indicate that HIV-associated Kaposi's sarcoma could be associated with HLA-A28, and therefore might be a different etiologic entity than HIV-infection alone. PMID- 2595722 TI - HLA Bw46 and DR9 associations in Graves' disease of Chinese patients are age- and sex-related. AB - The HLA-A, -B antigens in 159 Chinese patients with Graves' disease were compared with those of 330 controls. The HLA-DR antigens of the patients were also studied in 100 normals. Analysis of the increased prevalence of Bw46, according to the sex and age of onset of disease of the patients, showed that the strong association of Bw46 resided with male patients (n = 58), Pc = 0.0000052, RR = 4.2. Although the frequency of Bw46 was also increased in female patients (n = 101), it was statistically not significant. For the DR9 antigens, the strong association with male patients was also observed, viz. Pc = 0.019, RR = 3.2. Males also had higher risks of Graves' disease if they had homozygous Bw46 at presentation. Further analysis by age of onset of disease revealed the segregation of significant association with Bw46 for the males at 1-19 yr, Pc = 0.0011, RR = 17.5 HLA associations (Bw46 and DR9) with Graves' disease in Chinese are observed primarily in males, especially those whose known ages of onset of the disease are between 1-19 yr (Bw46). PMID- 2595723 TI - HLA linkage with familial vesicoureteral reflux and familial pelvi-ureteric junction obstruction. AB - The inheritance of HLA haplotypes has been looked at in a family with pelvi ureteric junction obstruction (PUJO) and two families with vesicoureteric reflux (VUR). The data have been combined with those of other reported families and lod scores calculated for both these urinary tract anomalies. There seems no doubt that VUR is linked to HLA whilst the case for PUJO is equivocal. PMID- 2595725 TI - Lack of association between HLA and rotator cuff rupture. PMID- 2595724 TI - Association of maternal HLA haplotypes with recurrent spontaneous abortions. AB - Histocompatibility typing was done on 63 women with idiopathic, recurrent abortions (greater than or equal to 3 consecutive, spontaneous abortions; summarized abortion rate: 92.8%), 112 of their full siblings and 101 parents. The distribution of full sisters sharing 2, 1 and 0 of the probands' haplotypes diverged from expected Mendelian segregation (p less than 0.05). Sisters sharing both the probands' haplotypes had an abortion rate of 59.1%, haploidentical sisters had an abortion rate of 25.0% whereas 6.3% of the pregnancies of the 0 haploidentical sisters had ended in miscarriage. The probands' HLA haplotypes included a significant (p less than 0.02) excess of HLA-A, B haplotypes which have previously been shown to exhibit features of positive linkage disequilibrium in Danes. Analysis of abortion rates among the probands and their siblings indicate that the idiopathic recurrent abortion syndrome and probably also the tendency to some sporadic abortions are inherited conditions determined by genes in the HLA region. The presented data may be compatible with an additive polygenic mode of inheritance with exclusive or predominant phenotypic expression in females controlled by an HLA linked spontaneous abortion susceptibility region (SASR). PMID- 2595726 TI - Association of HLA antigens with progressive systemic sclerosis and morphea. AB - The HLA phenotype frequencies of 40 patients with progressive systemic sclerosis (PSS) and 42 patients with morphea (sclerodermia circumscripta) indicate a weak, HLA-linked genetic predisposition of the affected individuals (70 female, 12 male). An "opposite" HLA A1, B8 (high immune response) vs A3, B7, DR2 (low immune response) constellation in PSS and morphea supports the clinical subdivision of scleroderma into these different nosological entities, and may serve as a differential diagnostic tool and prognostic marker. PMID- 2595727 TI - HLA class I antigens in severe RSV bronchiolitis. AB - Cytotoxic T-lymphocytes (CTL) recognize virus-infected cells in association with HLA class I antigens. There is strong evidence of the importance of CTL in respiratory syncytial virus (RSV) infections. We looked for but were unable to demonstrate an association between particular HLA class I antigens and severe RSV bronchiolitis in infants. PMID- 2595728 TI - Nonvalvular atrial fibrillation as a cause of fatal massive cerebral infarction in the elderly. AB - By studying 3,408 consecutive autopsied elderly patients, we found that two thirds of the 132 massive cerebral infarctions (86) were embolic, of cardiac origin. Embolic infarction associated with nonvalvular atrial fibrillation was seen in 48 cases (36%), half due to the first stroke. Embolic infarction associated with heart disease other than nonvalvular atrial fibrillation was seen in 23 cases (17%), and that from nonbacterial thrombotic endocarditis was seen in 15 cases (11%). Thrombotic infarction or infarction of nonembolic cardiac origin was found in only 39 cases (30%). Of 56 patients with fatal massive cerebral infarction who died less than or equal to 2 weeks after their stroke, 25 (45%) had embolic strokes associated with nonvalvular atrial fibrillation. Our study shows that nonvalvular atrial fibrillation is a very important cause of fatal massive cerebral infarction in the elderly. PMID- 2595730 TI - Hypercortisolism revealed by the dexamethasone suppression test in patients [corrected] with acute ischemic stroke. AB - Using the dexamethasone suppression test, we studied the activity of the hypothalamic-pituitary-adrenal axis within the first week after onset in 62 patients with acute ischemic stroke. Compared with two control groups (one comprising 25 elderly patients with various acute medical disorders and the other comprising 33 80-year-old volunteers), stroke patients had higher postdexamethasone cortisol levels (p = 0.08 and p = 0.001, respectively). By multiple regression analysis, high postdexamethasone cortisol levels in the stroke patients were significantly associated with proximity of the lesion to the frontal pole of the brain (p = 0.008) and with disorientation (p = 0.03), whereas no association with major depression was seen. Many stroke patients are exposed to hypercortisolism, which may have negative consequences upon organ functions. The extent to which dexamethasone administration suppresses cortisol levels seems to be determined mainly by the site of brain lesion and cannot be used as an indicator of major depression early after stroke. PMID- 2595729 TI - Short-term tranexamic acid treatment in aneurysmal subarachnoid hemorrhage. AB - Antifibrinolytic treatment for 4 weeks after a subarachnoid hemorrhage has been shown to have no effect on outcome since a reduction in the rate of rebleeding was offset by an increase in ischemic events. To determine if a shorter course (4 days) of antifibrinolytic treatment before the expected onset of ischemic complications might reduce the rate of rebleeding yet avoid ischemic complications, we prospectively studied a series of 119 patients with subarachnoid hemorrhage; 479 patients with subarachnoid hemorrhage from our previous randomized double-blind study (238 treated with placebo, 241 with long term tranexamic acid) served as historical control groups. At 3 months' follow up, the outcome of patients treated with short-term tranexamic acid was not different from that of patients treated with long-term tranexamic acid. The rate of rebleeding (24 of 119, 20%) was near that with placebo (56 of 238, 24%). In contrast, the rate of cerebral infarction (33 of 119, 28%) was almost identical to that after long-term tranexamic acid (59 of 241, 24%), although mortality from cerebral infarction was reduced. Compared with historical control groups, treatment with tranexamic acid for 4 days fails to reduce the incidence of rebleeding but still increases the rate of cerebral infarction. PMID- 2595731 TI - Cerebrovascular disease in rural Kashmir, India. AB - We studied the Kuthar Valley in the Anantnag District of south Kashmir (northwestern India) during the year 1986 to ascertain the prevalence and pattern of completed stroke. We detected 91 cases, giving a crude prevalence rate of 143/100,000. However, age-specific prevalence was 41/100,000 in the group aged 15 39 years and 630/100,000 in the group aged greater than or equal to 40 years; 69.23% of the cases were in men. Hypertension was present in 58.24% of the cases, while strokes due to valvular heart disease and puerperium-related strokes were most common in the young. Our study is first of its kind in this part of India. PMID- 2595732 TI - Effect of uridine 5'-diphosphate on cryogenic brain edema in rabbits. AB - This study was undertaken to examine the effect of uridine 5'-diphosphate, administered intravenously or intraperitoneally, on cold injury-induced brain edema in rabbits. Bolus injection or continuous intravenous infusion of uridine 5'-diphosphate 26 hours after a lesion was established had adverse effects, such as increased intracranial pressure and lowered systolic arterial blood pressure and cerebral perfusion pressure for approximately 10-29 minutes, but these parameters did not change appreciably from 29 minutes to 3 hours after administration. Intraperitoneally administered uridine 5'-diphosphate did not affect these parameters appreciably during 3 hours. Thus, the intravenous administration of uridine 5'-diphosphate is harmful under neurosurgical conditions. In contrast, 10 mg/kg/day i.p. uridine 5'-diphosphate pretreatment and posttreatment, beginning 24 hours before and continuing until 24 hours after the insult, significantly reduced neurologic abnormalities, Evans blue extravasation, water content in the injured gray matter, and intracranial pressure without affecting water content in the white matter. Intravenous dexamethasone pretreatment and posttreatment in this setting significantly reduced only neurologic abnormalities. However, there were no significant differences between intraperitoneal uridine 5'-diphosphate and intravenous dexamethasone effects on cold-injured brain. PMID- 2595733 TI - Preoperative training modifies radial maze performance in rats with ischemic hippocampal injury. AB - Rats exposed to 30 minutes of four-vessel occlusion reliably develop severe bilateral CA1 hippocampal injury; under certain conditions of radial maze training, such rats perform the reference memory component as well as controls yet perform the working memory component worse than controls. Reference memory is thought to depend on invariable and working memory on variable spatial information. We assessed the effect of training before ischemia. In Experiment 1, rats trained for 36 trials on 12-arm radial mazes before ischemia demonstrated a persistent impairment on the working memory task but eventually performed the reference memory task comparable to controls. Ischemic rats made more working memory errors as the number of choices increased. This pattern of working memory errors was similar to that in controls except, as expected, ischemic rats made many more errors. In Experiment 2, training for 80 trials before ischemia in rats decreased the severity of both the working and the reference memory impairment. Ischemia did not affect motor behavior in either experiment. These results characterize the working memory deficit in ischemic rats and demonstrate the importance of experimental factors, particularly in the design of treatment strategies to reduce functional impairments caused by ischemia. PMID- 2595734 TI - Fatal strokes in hyperglycemic cats. AB - Hyperglycemia is associated with three- to fourfold larger infarcts than normoglycemia following permanent middle cerebral artery occlusion in cats. We investigated the effects of glycemia on brain outcome when middle cerebral artery blood flow was restored (clip release) after 4 hours of occlusion. Seven of 13 hyperglycemic (22 mM) and one of 12 normoglycemic (6 mM) anesthetized cats developed total middle cerebral artery territory infarcts and hemispheric edema and died of brainstem compression. The remaining six and 11 cats recovered fully and later showed no or only small infarcts. Compared with permanent occlusion, restoration of blood flow after 4 hours reduced infarct volume in all normoglycemic and hyperglycemic cats that survived, but caused a much higher proportion (54% vs. 17%) of hyperglycemic and, for the first time, one normoglycemic cat, to die of infarct extension, hemorrhagic infarct conversion, and total territory edema. Thus, clip release after 4 hours caused some cats to show reduced and others to show augmented tissue damage. Rendering cats hyperglycemic substantially worsened their outcome after reperfusion by increasing their death rate from total territory edema sevenfold. Our results demonstrate that risk/benefit analyses for recanalization efforts in humans should take serum glucose concentrations into account. PMID- 2595735 TI - Influence of antihypertensive treatment with budralazine on autoregulation of cerebral blood flow in spontaneously hypertensive rats. AB - We studied the effect of chronic antihypertensive treatment with budralazine on the lower blood pressure limit of cerebral blood flow autoregulation using spontaneously hypertensive rats. Cerebral blood flow in the parietal cortex and caudate nucleus was measured to determine the lower limit using the hydrogen clearance method. The lower limit in both cerebral regions was significantly higher in 10 untreated spontaneously hypertensive rats than in 10 Wistar-Kyoto rats. The upward-shifted lower limit was restored to close to normal in the caudate nucleus and was partially restored in the parietal cortex of nine rats by 9 weeks of treatment with the high dose (50-68 mg/kg/day) of budralazine, which kept blood pressure constant at approximately normotension during the treatment period; the lower limit was slightly restored in both cerebral regions of seven rats by 4 weeks of treatment with the high dose. However, 9 weeks of treatment with the low dose (19-27 mg/kg/day) of budralazine, which produced moderate continuous hypotension in nine rats, did not apparently influence the lower limit. Our results suggest that long-term antihypertensive therapy with budralazine reduces the upward-shifted lower blood pressure limit of cerebral blood flow autoregulation toward normal and that the restoration induced by budralazine depends on the degree of blood pressure reduction as well as on the duration of the therapeutic period. PMID- 2595736 TI - Etiology of stroke in patients with Wernicke's aphasia. AB - We reviewed 49 patients with Wernicke's aphasia resulting from a stroke. Their aphasia was classified on the basis of comprehensive neuropsychological testing. Wernicke's aphasia was more common in older patients and in men. Cerebral infarction occurred in 38 patients (78%) and intracerebral hemorrhage in seven (14%); the remaining four patients (8%) developed aphasia after surgery for aneurysmal subarachnoid hemorrhage. Embolic events were the most common etiology of Wernicke's aphasia in the 38 patients with cerebral infarction, with cardiac emboli in 40% and large-vessel atheroemboli from a carotid source in 16%. In patients with Wernicke's aphasia secondary to infarction, an embolic source should be sought. Patients with Wernicke's aphasia should have computed tomography to exclude intracerebral hemorrhage before institution of anticoagulant therapy. PMID- 2595737 TI - Fusiform aneurysm of the vertebrobasilar arterial system. AB - We retrospectively evaluated the clinical features and therapeutic outcomes in 13 consecutive patients with the diagnosis of fusiform aneurysm of the vertebrobasilar system. Four patients (31%) presented with compressive symptoms and 10 (77%) with ischemic symptoms; one patient presented with both types of symptoms. No patient presented with rupture of the fusiform aneurysm. Based on the attending physician's choice, treatment included antiplatelet therapy in five patients, anticoagulation in seven, and no medication in one. Five patients died, four treated with antiplatelet agents and one not treated with any medication. The cause of death was progressive brainstem ischemia in three, sepsis in one, and gastrointestinal bleeding in one patient. All seven patients who received anticoagulants were alive, with no recurrence of symptoms or hemorrhagic complications after a mean follow-up period of 18 months. Based on previous and current series, we conclude that rupture of fusiform aneurysms is rare. Our results suggest a more favorable outcome in the management of these aneurysms with anticoagulation therapy to prevent progressive thrombosis and embolization. PMID- 2595738 TI - Bacterial cavernous sinus aneurysm treated by detachable balloon technique. AB - We describe a patient who developed bilateral cavernous sinus septic thrombosis secondary to a suppurative lesion on the left cheek. Despite clinical improvement, left oculomotor symptoms recurred suddenly. A carotid artery aneurysm within the cavernous sinus was diagnosed by means of magnetic resonance imaging and confirmed by digital angiography. Follow-up angiograms showed an initial decrease in the aneurysm size, with subsequent enlargement. A latex contrast-filled balloon was successfully placed within the aneurysm, preserving the carotid parent artery blood flow. Our case illustrates the usefulness of the detachable balloon technique in the treatment of bacterial aneurysms of the cavernous sinus as an alternative treatment to carotid artery ligation. PMID- 2595739 TI - Cerebral infarction in hereditary spherocytosis. PMID- 2595740 TI - 6-mercaptopurine plasma levels in children with acute lymphoblastic leukemia: relation to relapse risk and myelotoxicity. AB - Plasma levels of 6-mercaptopurine were determined in 22 consecutive children with acute lymphoblastic leukemia on oral remission maintenance therapy during the time period of August 1984 to January 1988. Each child received the drug once daily for up to 3 years and was studied repeatedly (1-12 times). An HPLC method was used for drug analysis. We found large interpatient variations in the mean peak plasma concentration (range of 50-424 ng/ml) and in the mean area under the concentration vs. time from 0-4 h curve (range of 82-637 ng ml-1 h). There were also pronounced variations between different sampling occasions in the same patient. Nine of the 22 patients had complications during the maintenance therapy. Five children with a mean peak plasma level below 135 ng/ml and a mean area under the curve (AUC) value below 251 ng ml-1 h relapsed (three in the central nervous system and two in the bone marrow). Both children with a bone marrow relapse died. Relapse risk was related to the AUC (p less than 0.05). Four children with a mean peak plasma level above 166 ng/ml and a mean AUC value above 363 ng/ml/h developed severe myelotoxicity, which necessitated a temporary cessation of the maintenance therapy. In addition, two patient relapsed 6 and 11 months after termination of maintenance therapy. Their mean peak and AUC values were not low but the concentrations decreased markedly towards the end of the maintenance period. The results indicate that the plasma levels of 6 mercaptopurine, when determined repeatedly, might be of significance for the outcome of the remission maintenance treatment. PMID- 2595741 TI - Intra- and interindividual variability in the free fraction of cyclosporine in plasma in recipients of renal transplants. AB - The protein binding of cyclosporine (CyA) in plasma was studied in serial samples for 6 months after transplantation in 66 renal transplant recipients. Analysis was performed with a recently developed method of equilibrium dialysis in steel chambers. Among the 1,848 samples, the free fraction ranged from 0.5 to 4.2%, with a median of 1.30%. The free fraction of CyA was highest immediately after transplantation (1.66 +/- 0.49%). Diabetics had a higher free fraction of CyA than nondiabetics during the first 2 weeks after transplantation. A weak, but significant, covariation was observed between the serum concentration of albumin or bilirubin and the free fraction of CyA (r = -0.47 and r = 0.39, respectively; p less than 0.01). There was also a significant correlation between serum HDL cholesterol (r = -0.39 to -0.48; p less than 0.01), as well as apolipoprotein A1 (r = -0.35 to -0.49; p less than 0.01), and the free fraction of CyA. A significant drop in the free fraction of CyA was observed immediately prior to acute rejection episodes as compared with 1 week earlier (p less than 0.01), but there was no difference in the free fraction of CyA between patients who lost their graft and those who did not. There was an overall eightfold variation in the free fraction of CyA in plasma, with an up to fivefold intraindividual variation and a 2.3-fold variation in the mean free fraction between individuals. A significant covariation was observed between the free fraction of CyA and the concentration of binding proteins in plasma, as well as factors such as time after transplantation, diagnosis, and clinical events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2595743 TI - Prediction of imipramine serum levels in enuretic children by a Bayesian method: comparison with two other conventional dosing methods. AB - The aim of the present study was to characterize the kinetic behavior of imipramine (IMI) and desipramine in enuretic children and to evaluate the performance of different methods for dosage prediction based on individual and/or population data. The study was carried out in 135 enuretic children (93 boys) ranging in age between 5 and 13 years undergoing treatment with IMI in variable single doses (25-75 mg/day) administered at night. Sampling time was one-half the dosage interval at steady state. The number of data available for each patient varied (1-4) and was essentially limited by clinical criteria. Pharmacokinetic calculations were performed using a simple proportional relationship (method 1) and a multiple nonlinear regression program (MULTI 2 BAYES) with two different options: using the ordinary least-squares method (method 2) and the least-squares method based on the Bayesian algorithm (method 3). The results obtained point to a coefficient of variation for the level/dose ratio of the drug (58%) that is significantly lower than that of the metabolite (101.4%). The forecasting capacity of method 1 is deficient both regarding accuracy [mean prediction error (MPE) = -5.48 +/- 69.15] and precision (root mean squared error = 46.42 +/- 51.39). The standard deviation of the MPE (69) makes the method unacceptable from the clinical point of view. The more information that is available concerning the serum levels, the greater are the accuracy and precision of methods (2 and 3). With the Bayesian method, less information on drug serum levels is needed to achieve clinically acceptable predictions. PMID- 2595742 TI - Evaluation of aminoglycoside disposition in patients previously treated with cisplatin. AB - The alterations in aminoglycoside disposition in patients previously treated with cisplatin were determined by reviewing the medical records of 37 cancer patients. The patients received 44 courses of an aminoglycoside antibiotic (gentamicin, n = 27; amikacin, n = 14; and tobramycin, n = 3). The mean (SD) half-life of 171 (120) min was greater than our previously published mean aminoglycoside half-life in children with cancer who were not receiving cisplatin. Twenty-five of 44 courses were completed without an aminoglycoside dosage reduction and only 5 courses were discontinued because of delayed aminoglycoside elimination. There was no significant difference in the duration of aminoglycoside therapy between the group that had a dosage reduction and the group that did not [6.6 (2.3) versus 5.8 (2.9) days, p = 0.42, respectively]. Multiple linear regression analysis of patient variables identified serum creatinine and cumulative cisplatin dose as the best predictors of aminoglycoside half-life (r2 = 46.0%, p less than 0.001). The only predictor of aminoglycoside clearance was serum creatinine (r2 = 35.2%, p less than 0.001). Patients previously treated with cisplatin are at greater risk for delayed aminoglycoside elimination. Prior administration of cisplatin is not an absolute contraindication to the use of aminoglycoside antibiotics. When clinically indicated, patients who have previously received cisplatin and have apparently normal renal function should be treated cautiously with standard doses of aminoglycoside antibiotics, and pharmacokinetic monitoring should be routinely performed. PMID- 2595744 TI - Prediction of the optimal perphenazine decanoate dose based on blood samples drawn within the first three weeks. AB - During a 3-month period, 52 paranoid psychotic inpatients were treated with perphenazine decanoate (Trilafon decanoate) in order to determine a treatment schedule ensuring perphenazine serum levels within the optimal range (2-6 nmol/L). All patients received 1 ml (108 mg) perphenazine decanoate on days 0, 7 and 21, after which the doses and intervals were individually adjusted according to the clinical condition. It was shown that the sum of 2 measurements of perphenazine concentration early during treatment, viz., on days 14 and 21, correlates strongly (r = 0.96) with the steady-state level obtained after 3 months. Consequently, a nomogram for dose and length of interval could be elaborated giving steady-state serum levels of perphenazine of about 4 nmol/L, i.e., in the middle of the optimal concentration range. PMID- 2595745 TI - Dosing accuracy of antiepileptic drug regimens as determined by serum concentrations in outpatient epilepsy clinic patients. AB - To evaluate the ability of clinicians to accurately dose antiepileptic drugs (AEDs), 2,958 serum concentrations in two outpatient epilepsy clinics were studied. Serum concentrations of phenytoin (PHT) were significantly less likely to fall within the therapeutic range (TR) when compared to carbamazepine (CBZ) or phenobarbital (p less than 0.0001) even when there was evidence that patient compliance was good. This difference remained significant when the second through fourth follow-up serum concentrations were analyzed. PHT concentrations were more likely to be below than above the TR (p less than 0.0001). CBZ concentrations were least likely of the three AEDs to be below the TR (p less than 0.01). Analysis of factors influencing AED metabolism and of data from previous studies implies that saturable metabolism and variable time to steady state for PHT are responsible for these findings. These results support the increased use of dosing aids for PHT that may help clinicians more accurately choose PHT doses and estimate time to steady state. PMID- 2595747 TI - No effect of terodiline on anticoagulation effect of warfarin and steady-state plasma levels of warfarin enantiomers in healthy volunteers. AB - The influence of terodiline (25 mg b.i.d.) on the anticoagulant effect and plasma levels of warfarin enantiomers was studied in 23 young healthy male volunteers. Racemic warfarin was first given for 24 days to determine the doses required for the subject's vitamin K-dependent coagulation factors to fall within 10-20% of the normal range, as determined by the Thrombotest. During continuous warfarin treatment (mean daily dose 5.3 mg, range 2.5-9.4 mg), terodiline or placebo was given for two weeks in a randomized and double-blind fashion, and then the drugs were crossed over and given for another two weeks. Terodiline did not influence the anticoagulant effect of warfarin or the plasma levels of the warfarin enantiomers. The results indicate that it should not be necessary to monitor patients on combined therapy with terodiline and warfarin more frequently than patients on warfarin monotherapy. PMID- 2595746 TI - Time-dependent pharmacodynamic effects of phenobarbital in humans. AB - The relationship between the serum concentration of phenobarbital and its pharmacodynamic effects was assessed in a double-blind controlled study in eight normal volunteers who were given single oral doses of phenobarbital (200 mg) and placebo according to a randomized cross-over design. Compared with the placebo session, phenobarbital was found to induced CNS-depressing effects as assessed by visual analogue rating scales (VARS) and critical flicker fusion tests (CFF), whereas no significant effects were detected on choice reaction times, tappings, and digit symbol substitutions. There was a clear-cut dissociation between the time course of serum phenobarbital levels, which remained at a plateau throughout most of the period of observation (up to 72 h) and its subjective (VARS) and objective (CFF) effects, which could be documented only for up to 9 h after administration. These data suggest that pharmacodynamic tolerance develops rapidly even after a single oral dose of the drug. Multiple Sleep Latency Tests (MSLTs) were also performed in the same subjects and showed that phenobarbital increases diurnal drowsiness and attenuates the circadian variation in drowsy state that is seen under control conditions. MLSTs appeared to be superior to other tests in documenting the sedative effects of the barbiturate. PMID- 2595748 TI - Heparin pharmacokinetics during hemodialysis. AB - The disposition of heparin was studied in 21 chronic hemodialysis patients. Heparin was administered as a bolus injection in doses of 3,000-12,000 U. Combined zero and first-order elimination was demonstrated, with heparin half life declining by 74% over 3.5 h during dialysis. Assumption of a first-order pharmacokinetic model of elimination resulted in a mean difference of 0.001 U/ml between actual and predicted heparin concentrations. Mean first-order pharmacokinetic parameters were: half-life, 117 min; heparin volume of distribution (V), 68 ml/kg; clearance, 28 ml/min. A high degree of interpatient variability was also observed. A comparison of V and plasma volume (PV) revealed V to be significantly greater than PV (p less than 0.001), indicating distribution outside the plasma compartment. When compared to blood volume, there was no significant difference (p greater than 0.1), indicating that blood volume may be used to approximate V. The nonlinear component of the elimination process is not clinically significant within the range of therapeutic plasma concentrations used during hemodialysis, but the high degree of interpatient variability indicates that dosage individualization may be useful. PMID- 2595749 TI - Digoxin elimination in a functionally anephric patient after digoxin-specific Fab fragment therapy. AB - The elimination of total digoxin after digoxin-specific Fab fragment therapy in a patient in end-stage renal disease is described. Two-component, nonlinear exponential regression of the patient's total digoxin concentration data revealed biphasic elimination: a fast phase with a half-life of 43 h and a slow phase with a half-life of 330 h. Serum total digoxin concentration decreased 20% 12 h after the initiation of Fab fragment therapy. The mean serum concentrations of total digoxin and apparent total digoxin as measured by fluorescence polarization immunoassay during a 520-h period after the initiation of therapy were 18.42 and 14.77 ng/ml, respectively (n = 15). The correlation between the two measurements was good (r = 0.987). The time course of free digoxin concentration obtained after ultrafiltration at 2, 20, or 37 degrees C is also described. The free digoxin concentrations (n = 10) at these temperatures averaged over a 282-h period were 0.35, 0.53, and 0.82 ng/ml, respectively (p less than 0.001, 2 degrees C vs. 37 degrees C). PMID- 2595750 TI - Human scalp hair as evidence of individual dosage history of haloperidol: prospective study. AB - The concentration of haloperidol in hair was measured by radioimmunoassay after hairs were dissolved in 2.5 N NaOH solution and the drug was extracted. In patients to whom haloperidol had been administered at fixed daily doses for more than 1 month, and in whom therapy had been just discontinued (group A, n = 5) or the doses cut to half (group B, n = 3), hairs were collected when the dose was changed and at 1 and 2 or 3 months thereafter. A few strands of hair collected on each occasion were cut into 1-cm-long portions from the roots, and the haloperidol concentration was measured in each portion. When hairs were assumed to grow at a rate of 1-1.5 cm/month, the portion of hair that reflected the change of dose was observed to move upward along the hair length in all patients of group A. However, these phenomena were less obvious in group B. These results indicate that at the least, hair could serve as an indicator of individual exposure or nonexposure to haloperidol and could yield retrospective information. In rats whose hairs had been removed by plucking from an area on the back, either saline or 1 mg/kg of haloperidol (i.p., b.i.d.) was administered for 2 weeks (first period), followed by 0, 0.5, 1, or 2 mg/kg b.i.d. for the subsequent 2 weeks (second period). At the end of each period, hairs that had grown in the plucked area were collected. Within-groups, haloperidol levels in hairs collected at the end of each period corresponded to the doses given.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2595751 TI - The use of aerosolized tobramycin in the treatment of a resistant pseudomonal pneumonitis. AB - Aerosolized tobramycin was given to a 68-year-old man with resistant Pseudomonas aeruginosa pneumonitis at a dose of 100 mg every 8 h via a tracheostomy, after the patient failed to respond adequately to parenteral aminoglycoside and ticarcillin therapy. Minimum inhibitory concentration and minimum bactericidal concentration for tobramycin and gentamicin were 16 micrograms/ml and greater than 16 micrograms/ml, which necessitated aerosol administration. Tracheal concentrations 15 min and 4 h after a dose were 1,560 and 930 micrograms/ml. The patient responded and eventually was discharged from the hospital. Thus, monotherapy with an aerosolized aminoglycoside may be effective in some patients with resistant Pseudomonas aeruginosa pneumonitis. PMID- 2595752 TI - A radioreceptor assay for the measurement of cyclosporine activity: a preliminary report. AB - Cyclosporine A (CsA) is extensively metabolized in the liver. Some of the known metabolites share immunosuppressive properties with the parent drug. Furthermore, CsA therapy is used in an increasing number of clinical conditions, some of which affect the pharmacokinetics of the drug. At this time, it is not yet known if CsA or its metabolites are responsible for the nephrotoxicity or hepatotoxicity observed in some individuals. Some high-performance liquid chromatography (HPLC) and monoclonal immunoassay procedures measure parent drug and not the pharmacologically active metabolites, while polyclonal immunoassays and nonspecific monoclonal antibody immunoassays measure both parent drug and metabolites. However, it is unlikely that the degree of cross-reactivity with metabolites correlates with their immunosuppressive effect. To overcome these drawbacks, we have developed a method of measuring CsA activity in whole blood using specific receptors from the cytosol of human mononuclear leukocytes that have been semipurified through ultracentrifugation. The basis of the procedure is the competitive binding at specific receptor(s) between a constant concentration of [3H]dihydrocyclosporine and the variable concentrations of cyclosporine and its pharmacologically active metabolites in whole blood. Comparisons between six different assays (three specific, two nonspecific, and the receptor assay) were made. Overall, the two specific radioimmunoassay procedures correlated well to HPLC, while correlation of the two nonspecific immunoassay procedures to HPLC was poor. Poor correlation was also found to exist between the radioreceptor assay and the nonspecific assays, indicating that the cytosolic binding of CsA and its metabolites cannot be correlated to currently available assays. PMID- 2595753 TI - An improved sensitive assay for simultaneous determination of plasma haloperidol and reduced haloperidol levels by liquid chromatography using a coulometric detector. AB - A simple, highly sensitive and specific high-performance liquid chromatographic method that uses a coulometric detector for the simultaneous assay of haloperidol and reduced haloperidol in human plasma has been developed, using bromoperidol as the internal standard. A reversed phase C8 5-microns column (25 x 0.46 cm) and a mobile phase of phosphate buffer (pH 7.0), acetonitrile, and methanol (40:20:40 vol/vol) are used for separating the analytes. The analytes are extracted from alkalinized plasma using a mixture of pentane and isopropanol (95:5 vol/vol) and purified by back extraction into a perchloric acid solution. Teflon tubes with screw caps are used throughout the extraction work. The compounds are oxidized at a potential of +0.90 V against a Ag/AgCl reference electrode. The detection limit of the assay is 50 ng/L using 1 mL of plasma. The average interassay coefficient of variation for samples of concentration 1-40 micrograms/L is approximately 8%. Possible drug interferences in the assay have been studied. The absolute recovery of the method is approximately 80%. The assay has been validated by quantitating 150 schizophrenic patients' samples. PMID- 2595754 TI - Reactivity considerations in the analysis of glucuronide and sulfate conjugates of diflunisal. AB - Reactivity of glucuronide and sulfate conjugates was taken into account in development of a simple isocratic HPLC method for direct assay of diflunisal (DF) and its acyl glucuronide (DAG), phenolic glucuronide (DPG), and sulfate (DS) conjugates. Whereas DPG was stable over the pH range 0-9, DAG was highly labile at neutral to slightly alkaline pH, undergoing rearrangement (isomerisation via acyl migration), hydrolysis, and in the presence of methanol, transesterification to DF methyl ester. The 2-, 3-, and 4-O-acyl positional isomers of DAG appeared as three pairs of peaks. Interconversion between partners of each pair occurred even under acidic conditions inhibitory to acyl migration, implicating mutarotation. DS was stable at neural to slightly alkaline pH, but underwent hydrolysis under relatively strongly acidic conditions. However, this hydrolysis was remarkably catalyzed (e.g., by 1,000-fold) in the presence of solvents (i.e., solvolysis) such as diethyl ether and ethyl acetate. DS (an acid) could not be extracted from aqueous solution because of this acidic solvolysis. Suitable conditions for simultaneous direct analysis (nonextractive, nonconcentrative) of DF and its reactive (DAG and DS) and unreactive (DPG) conjugates were achieved by working at pH of approximately 4.5. The procedure thus developed is suitable for plasma, urine, and bile samples, and has revealed the presence of new, as yet unidentified, metabolites of DF. PMID- 2595756 TI - Interference from a Red Top Venojet tube in high-performance liquid chromatographic analysis. PMID- 2595755 TI - Diazepam treatment does not influence the debrisoquine or mephenytoin hydroxylation phenotyping tests. AB - Debrisoquine and S-mephenytoin hydroxylation phenotyping tests were performed in 9 patients before and during treatment with diazepam at a daily dose of 10 or 15 mg. There was no change in either the debrisoquine/4-hydroxydebrisoquine ratio or the ratio of S/R mephenytoin in urine. The hydroxylation of these two test drugs is apparently not inhibited by administration of therapeutic doses of diazepam. PMID- 2595757 TI - Comparison of digoxin-like immunoreactive substance cross-reactivity with two digoxin automated immunoassay. PMID- 2595758 TI - Interactions of glycolytic enzymes. PMID- 2595759 TI - Glutamine and protein turnover. PMID- 2595760 TI - Lymphoma and hypercalcemia in a pediatric orthotopic liver transplant patient. AB - We present a case report of a pediatric orthotopic liver transplant recipient who developed lymphoma with hypercalcemia on cyclosporine and prednisone immunosuppression. This is the first reported posttransplant lymphoproliferative disorder complicated by hypercalcemia, with a finding of an elevated 1,25 dihydroxyl vitamin D state, suggesting that it has a role in the pathophysiology of this B cell lymphoma hypercalcemia. The clinical course and management of this disorder with a 31-month follow-up are described. PMID- 2595761 TI - Pontine and extrapontine myelinolysis following liver transplantation. Relationship to serum sodium. AB - The relationship between central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) and serum sodium changes in the setting of orthotopic liver transplantation (OLT) is examined. Postmortem examination of 14 patients with end stage liver disease who underwent liver transplantation revealed CPM in four, of which three also had EPM. A retrospective review of clinical and laboratory data was performed on all patients. There were marked perioperative rises (21-32 mEq/L) in the serum sodium concentration in all four patients who developed myelinolysis. In contrast, the largest increase in sodium in patients without demyelination was 16 mEq/L. We conclude that perioperative rises in the serum sodium concentration increase the risk of myelinolysis. CPM and EPM should be considered if the patient develops mental status changes or focal neurological deficits several days after OLT. PMID- 2595762 TI - The role of MHC and non-MHC antigens in the rejection of intracerebral allogeneic neural grafts. AB - Embryonic DA retinal allografts that have survived for prolonged periods after having been transplanted into the brains of neonatal BN rats can be induced to reject following peripheral sensitization with a DA skin graft. The results show that histocompatibility antigens play the major role in the rejection of grafts placed in the CNS and that a disparity between the retinal and skin grafts for MHC antigens induces a more severe rejection response than does a non-MHC antigen disparity. PMID- 2595763 TI - Evidence that long-term bone marrow culture of patients with multiple myeloma favors normal hemopoietic proliferation. AB - Long-term bone marrow cultures (LTBMC) were initiated with marrow aspirate cells from 12 patients with multiple myeloma (MM) using the Dexter system. The myeloid and the neoplastic myeloma cell growths were evaluated for up to 6-9 weeks. Our results demonstrate the development of an adherent layer capable of supporting normal granulopoiesis with a concomitant drop in the growth of myeloma cells. The B lymphocyte monoclonal proliferative compartment was also studied with bromodeoxyuridine (Brdurd), an analog of thymidine incorporated during the S phase, and the labeling index was calculated. The ability to form myeloma stem cell colonies in a modified plasma clot short-term assay was also evaluated. The results confirmed that the neoplastic B lineage compartment was not able to grow in Dexter's system for more than 4 weeks in 11 of 12 cases studied, with the disappearance of Brdurd-positive cells after two weeks, whereas LTBMC were able to sustain the growth of myeloid progenitors. These data indicate the potential applicability of this culture method in selecting normal hematopoietic progenitors from patients with multiple myeloma. This approach can have significant implications for aggressive treatment of patients with multiple myeloma, especially in trials involving autologous bone marrow transplantation (ABMT). PMID- 2595764 TI - A detailed analysis of the potential of water-soluble classical class I MHC molecules for the suppression of kidney allograft rejection and in vitro cytotoxic T cell responses. AB - Water-soluble classical (RT1-A) class I MHC molecules were purified from aqueous extracts of DA strain liver. Following monoclonal antibody affinity, lentil lectin affinity, and gel filtration chromatography, 600 micrograms of soluble RT1 A class I molecules with antigen activity equivalent to 1.3 x 10(11) nucleated DA spleen cells (greater than 500 DA spleens) was obtained. Both PVG and LEW strain recipients of DA kidney allografts were pretreated with intravenous injections of the DA soluble class I molecules, in doses with antigen activity equivalent to 10(8) nucleated DA spleen cells. Three protocols of pretreatment were used: twice weekly injections for 4-5 weeks, with grafting 3 or 4 days after the last injection; a single injection 7 days pregraft; or a single injection 1 day pregraft. The PVG and LEW rats received the soluble class I pretreatment either alone or in combination with suboptimal doses (2 mg/kg/day) of cyclosporine after grafting, making a total of 12 experimental groups treated with soluble class I antigen. In no case did treatment with soluble class I antigen elicit an antibody response in prospective graft recipients; influence kidney graft survival in any way; or enhance or suppress the antibody response to the kidney graft. The soluble DA class I MHC molecules were tested in vitro for their effect on the generation and effector function of allospecific PVG and LEW anti DA RT1-A class I cytotoxic T cells and TNP specific, self RT1-Aa restricted cytotoxic T cells. Concentrations up to 5 micrograms/ml (10(-7) M), equivalent to 10(9) nucleated DA spleen cells/ml, were without any effect. We conclude that monomeric forms of water-soluble classical class I molecules are poor immunogens--and, at doses conventionally used for active enhancement, do not influence cytotoxic T cell responses and have little potential for donor-specific immunosuppression. PMID- 2595765 TI - Induction of a syngeneic graft-versus-host disease-like syndrome in DBA/2 mice. AB - Syngeneic graft-versus-host disease has been shown to occur in syngeneic rat radiation chimeras after treatment with a short course of CsA. However, data concerning this model have been controversial in murine systems. We have successfully induced a GVHD-like syndrome in syngeneic mouse radiation chimeras treated transiently with CsA. Lethally irradiated (950 rads) DBA/2 mice were reconstituted with syngeneic bone marrow and treated daily, i.p. with 15 mg/kg CsA in olive oil for 21 days. Within 1 week after discontinuing CsA, animals developed clinical signs of GVHD including runting, hunched posture, and severe diarrhea. This disease was fatal for greater than 80% of treated animals within 4 weeks after cessation of CsA. Furthermore, the induction of syngeneic GVHD did not appear to be linked to a particular MHC haplotype. Histologically, there was pronounced lymphoid atrophy of the spleen and thymus. Sections of large intestine showed an acute inflammatory process involving the mucosal layer ranging from single-cell destruction to complete mucosal ulceration. This murine model of GVHD should provide new opportunities for studying the development and regulation of autoimmune processes. PMID- 2595766 TI - Effects of combined cholera toxin and cyclosporine therapy on renal allograft survival in the rat. PMID- 2595767 TI - Successful twin pregnancies in renal transplant recipients taking cyclosporine. PMID- 2595768 TI - Clinical evaluation of PBS140 solution for cadaveric renal preservation. PMID- 2595770 TI - Calcium channel blockers and cyclosporine metabolism. PMID- 2595769 TI - Evidence from 31P nuclear magnetic resonance studies of cardiac allografts that early rejection is characterized by reversible biochemical changes. PMID- 2595771 TI - Local prednisolone infusion of canine renal allografts. PMID- 2595772 TI - The use of routinely available clinical data in differentiating renal allograft rejection from cyclosporine nephrotoxicity. PMID- 2595773 TI - Error in description of virus antigen system. PMID- 2595774 TI - Pituitary function in brain-dead patients. PMID- 2595775 TI - Use of OKT3 in liver transplant patients. PMID- 2595776 TI - A technique for liver transplantation in the rat. PMID- 2595777 TI - Glycolytic support of adenine nucleotides in rat liver flush-preserved with UW or Collins' II. Importance of donor nutritional status. AB - Correlation of hepatocellular adenine nucleotides in donor liver with clinical posttransplant outcome has recently been reported. Our earlier work with rats has shown that pretreatment of donors with glucose effectively retards hepatocellular ATP losses in livers preserved in Collins' II solution through potentiation of their glycolytic capacity. The primary substrate--i.e., endogenous or exogenous glucose--was not identified. The current study was undertaken to compare the relative efficacy of the University of Wisconsin (UW) solution, which is devoid of glucose, with Collins' II in the support of adenine nucleotides through anaerobic glycolysis in flush-preserved rat liver. Adult rats were either pretreated with 25% dextrose or fasted prior to liver harvesting and preservation in either UW or Collins' II. Adenine nucleotide degradation and lactate production during preservation were assessed. For a given dietary pretreatment, losses of ATP and adenylate energy charge and lactate production were similar for UW- and Collins' II-preserved livers. Donor pretreatment with dextrose resulted in significantly higher ex vivo liver ATP, energy charge, and lactate regardless of the preservation solution. Salvageable nucleotide degradates were increased significantly in UW livers, presumably through the effects of allopurinol. These results demonstrate that effective support of adenine nucleotides by glycolysis in flush-preserved liver is independent of the presence of exogenous glucose but dependent upon the nutritional status of the donor prior to liver procurement. PMID- 2595779 TI - Interleukin 2 receptor in rat heart allograft rejection. AB - Soluble interleukin 2 receptors (S-R-IL-2) of truncated Tac chain, produced in vitro during T lymphocyte activation, may represent an in vivo marker of an alloimmune reaction. We analyzed serum S-R-IL-2 production during acute heart allograft rejection and compared soluble and membranous Tac chain (blood lymphocytes and graft invading cells) regulation during rejection. Serum S-R-IL-2 was tested in an immunoradiometric assay, with a combination of two mouse IgG1 anti-IL2-R mAbs (ART18 and OX39). Membranous Tac chain was analyzed by immunochemistry in graft tissue, and by immunofluorescence on blood and spleen leukocytes. Four experimental groups were used: untreated allogeneic, untreated syngeneic, CsA-treated (10 mg/kg/day for 15 days) allogeneic and CsA-treated syngeneic graft recipients. In the untreated allogeneic group, S-R-IL-2, tested every day until rejection (9.14 +/- 1.6 days), increased as early as day 3 after transplantation, peaked at day 6, and plateaued thereafter. The allograft was infiltrated at day 5 by Tac chain-positive cells (10% of OX1 cells and 84% of OX19 cells). A small percentage of mononucleated cells was labeled in blood, but not in spleen, by ART18 and OX39 at day 7 only. In contrast, in untreated syngeneic and CsA-treated allogeneic combinations, there was no increase of baseline S-R-IL-2 level (P less than 0.001), and graft infiltrate did not contain IL-2-R positive cells. CsA treatment prolonged heart allograft survival (41.3 +/- 2.8 days). Baseline S-R-IL-2 levels during treatment were lower than those observed in untreated animals. In the CsA-treated allogeneic group, after CsA treatment interruption, S-R-IL-2 levels significantly increased, reaching a plateau at day 37. Results suggest that S-R-IL-2 measurement can be useful for clinical diagnosis of allograft rejection. PMID- 2595778 TI - The UW solution for canine kidney preservation. Its specific effect on renal hemodynamics and microvasculature. AB - The preservation effects of UW solution on renal hemodynamics and microvascular systems were studied in canine kidney autografts. In 72-hr UW-preserved kidneys, the microvessels of both cortex and medulla were completely visualized with silicon rubber compound 1 hr after reperfusion. Histology also showed extremely well-preserved arterioglomerular and tubular systems. These results were correlated with good renal blood flow, prompt recovery of posttransplant graft function, and 100% two-week survival of dogs. In contrast, kidneys preserved for 72 hr with Euro-Collins solution showed necrotic and obstructive changes of the microvasculature and deterioration of renal hemodynamics. In 120-hr UW-preserved kidneys, the microcirculation of the medullary region became poor after reflow when there was fairly intact perfusion of the cortical region, indicating an ischemia-related intrarenal blood flow maldistribution. The 120-hr kidneys subsequently failed in spite of having a good blood flow and morphologically well maintained microvasculature after reperfusion. These data demonstrated that much, but not all, of the beneficial effect of UW solution in kidney preservation might be attributed to its remarkable protection of renal microvasculature. Correction of intrarenal blood maldistribution caused by a discrepancy in tolerance to ischemia of the vascular and tubular systems might be important in successfully preserving the kidney for 120 hr. PMID- 2595780 TI - Detection of cardiac allograft rejection and myocyte necrosis by monoclonal antibody to cardiac myosin. AB - Indium 111-labeled monoclonal antibody to cardiac myosin was examined for efficacy in the detection of cardiac graft rejection and rejection-related myocyte necrosis. Heterotopic heart transplants were performed in isogenic and allogenic groups of rats (n = 56). At selected intervals posttransplant, uptake of injected antibody in the donor and native hearts was determined by gamma scintillation scanning. Indium uptake was compared to histologic results graded for the severity of rejection and the presence of myocyte necrosis. The donor heart uptake of labeled antibody was significantly greater in both moderate rejection and severe rejection than in lesser degrees of rejection (P = 0.05). The donor/native heart antibody uptake ratio (AUR) in both severe and moderate rejection were significantly different from no or mild rejection (P = 0.05). In pooled grafts without myocyte necrosis, both the absolute donor heart antibody uptake and the donor/native heart AUR were significantly greater in grafts with moderate or severe rejection than in those with no or mild rejection (P less than 0.001). Among grafts with moderate or severe rejection, those with myocyte necrosis had greater donor heart antibody uptakes and greater donor/native heart AUR than grafts without myocyte necrosis (P less than 0.001). The grade of rejection and the presence of histologic myocyte necrosis appear to be closely related but independent variables, both of which influence antibody uptake. It is concluded that monoclonal antibody to cardiac myosin may be a useful noninvasive tool that could distinguish moderate or severe rejection from lesser degrees of rejection and that could detect the presence of myocyte necrosis. PMID- 2595781 TI - The pharmacokinetic advantage of local 6-mercaptopurine infusion in a canine renal transplant model. AB - In light of recent technologic advances, we developed a canine renal allograft model utilizing implantable, programmable infusion pumps and biocompatible catheters to reexplore the concept of local immunosuppression. Thirteen mongrel dogs underwent bilateral nephrectomy and autotransplantation of 1 kidney via end to-end renal-iliac artery and end-to-side renal-iliac vein anastomoses. The proximal end of an infusion catheter directed into the iliac artery was tunneled to a subcutaneously placed programmable pump. A second, sampling catheter was placed with its tip in the iliac vein just proximal to the venous anastomosis. During a period of i.a. infusion of heparinized saline ranging from 19 to 63 days, serum creatinine remained normal in all but 1 animal, which developed pyelonephritis and catheter-tip perforation of the iliac artery. No cases of arterial thrombosis or catheter migration were observed at necropsy. In 7 additional autotransplanted dogs, simultaneous iliac vein and systemic (jugular vein) concentrations of 6-mercaptopurine (6-MP), the major immunosuppressive metabolite of azathioprine, were determined during a continuous 24-hr i.a. infusion (10 mg/kg/24 hr). Following termination of the infusion, 10 mg/kg 6-MP was administered to the same 7 dogs as an i.v. bolus, and systemic drug concentrations were determined over a 4-hr period. Mean +/- SE total-body clearance and elimination half-life were 887 +/- 159 ml/min and 1.4 +/- 0.2 hr, respectively, in the i.v. bolus study, indicating that 6-MP is rapidly cleared from the systemic circulation. Unexpectedly, the kidney removed as much as 60-95% of locally infused 6-MP, reducing the amount of active drug entering the systemic circulation to 5-40% of that which would be present during an i.v. infusion of the same dose. According to the principles governing the advantages of i.a. infusions, these data demonstrate that 6-MP can be infused intrarenally to produce both a 4-fold increase in drug concentration within the kidney and an 80% decrease in systemic drug delivery when compared to same-dose i.v. administration. The overall result is the presence of a 30-fold gradient between local and systemic drug concentrations during intrarenal 6-MP infusion. We conclude that i.a. infusion of an immunosuppressive agent is technically feasible with preservation of renal function, and that 6-MP can be delivered locally in a canine model with great pharmacokinetic and potential therapeutic advantage. PMID- 2595783 TI - Characterization of lymphocytotoxic antibodies causing a positive crossmatch in renal transplantation. Relationship to primary and regraft outcome. AB - In a series of 123 renal transplants performed in the presence of a positive crossmatch (either peak positive-current positive or peak positive-current negative), we have analyzed the immunoglobulin class and specificity of the donor reactive antibodies. The immunoglobulin class was determined by dithiothreitol reduction and the specificity by cytotoxicity inhibition using monomorphic antibodies specific for HLA class I, DR, and DQ antigens. There was good primary graft and regraft survival in the presence of peak positive and current positive crossmatches due to IgM non-HLA antibodies. There was also acceptable primary graft and regraft survival with peak positive-current negative crossmatches due to T and B cell IgM HLA class I antibodies, but not with IgG HLA class I antibodies. Positive B cell crossmatches due to IgM or IgG HLA antibodies were associated with good primary graft survival but poor regraft survival. PMID- 2595782 TI - Local immunosuppression with reduced systemic toxicity in a canine renal allograft model. AB - We compared the efficacy of continuous intraarterial versus intravenous 6 mercaptopurine (6-MP) infusion in a mongrel canine renal allograft model with regard to overall survival, incidence of systemic and renal toxicity, and systemic drug exposure. Arterial anastomoses were done end-to-end, and infusion catheters were placed in the iliac artery or vena cava and connected to a subcutaneously placed programmable pump. A dose of 0.5 mg/kg/day 6-MP did not prolong survival over heparin-treated or untreated controls (MST = 7 days for both groups) when administered either locally or systemically. However, 0.75 mg/kg/day 6-MP i.a. (MST = 20 days) significantly prolonged survival over both untreated (P = 0.007) and heparin-treated controls (P = 0.02), with all dogs eventually dying of rejection. In contrast, 0.75 mg/kg/day i.v. (MST = 7 days) failed to prolong survival over controls (P greater than 0.1) and produced death from systemic toxicity in 3 of 7 animals. Six of 7 dogs receiving 2.0 mg/kg/day 6 MP i.a. (MST = 12 days) developed azotemia secondary to drug-induced nephrotoxicity. Identical renal histologic changes occurred in the same time frame in autotransplants treated similarly. Of 7 animals receiving 2.0 mg/kg/day i.v. (MST = 12 days), 5 died from early, severe systemic drug toxicity and 2 from early rejection. During 6-MP infusion at 0.5 mg/kg/day, systemic exposure was significantly less in the locally treated than in the systemically treated dogs when Cr concentrations were normal or moderately elevated (P less than 0.0005 and P = 0.01, respectively) but not when renal function became severely impaired (P = 0.34). In contrast to i.v. infusion, i.a. 6-MP delivery dissociated immunosuppressive efficacy from systemic toxicity, supporting previous work demonstrating high first-pass renal elimination of 6-MP. We conclude that tightly controlled local delivery of an immunosuppressive agent can effectively prolong graft survival with reduced systemic toxicity in a large animal model employing a pump/catheter system applicable to man. PMID- 2595784 TI - Platelet crossmatching for kidney transplants by flow cytometry. AB - Although flow cytometry crossmatching is now performed by many kidney transplant centers, it yields a high false-positive rate, as evidenced in the present series by a 71% one-month success rate despite a positive crossmatch. In an attempt to reduce false-positive reactions while retaining the sensitivity of the flow cytometer, platelets were tested as targets. Whereas flow cytometry with T cells was not correlated with one-month failure rates, retrospective platelet crossmatching by flow cytometry showed that kidney failure within one month occurred in 53% of 19 patients with a positive platelet crossmatch compared with 15% of 48 patients with a negative platelet crossmatch. (P less than 0.002). Statistical significance in one-month outcome was also obtained when only first transplant patients were analyzed (P less than 0.04). The present results suggest that crossmatching with platelet targets may be a simpler way to avoid early primary nonfunction while minimizing false-positive reactions. PMID- 2595785 TI - Methylprednisolone disposition in renal transplant recipients receiving triple drug immunosuppression. AB - Renal transplant patients commonly receive triple-drug immunosuppression with standardized doses of cyclosporine, azathioprine, and methylprednisolone. Although cyclosporine may decrease the clearance of oral prednisone, data are lacking for methylprednisolone, a glucocorticoid commonly prescribed via a standardized protocol for intravenous therapy and during periods of acute rejection. The disposition of methylprednisolone (doses: 10-60 mg/day) was examined in nine renal transplant patients during the post-transplant period (0.8 14 months). Plasma samples were collected over 24 hr and analyzed for methylprednisolone via HPLC. Pharmacokinetic parameters were determined by noncompartmental analysis. The mean total clearance of methylprednisolone was 379 ml/hr/kg (range 105-672) and the volume of distribution was 1.4 +/- 0.5 L/kg. The mean plasma half-life was 2.7 +/- 1.1 hr. When normalized to a 1 mg dose of methylprednisolone, the mean peak concentration at 1 hr was 10.0 +/- 3.5 ng/ml with an 8 hr concentration ranging from 0.3 to 5.5 ng/ml. An appreciable variability in methylprednisolone metabolism thus exists in renal transplant recipients receiving triple-drug immunosuppression. This may partially explain the variable response to steroid therapy during acute rejection episodes and chronic immunosuppression as well as the unpredictable occurrence of chronic steroid toxicity. PMID- 2595786 TI - Monitoring of bone marrow transplant recipient liver by fine-needle aspiration biopsy. AB - Acute graft-versus-host disease (aGVHD) of the liver was studied with fine-needle aspiration biopsies of thirty-four bone marrow transplant recipients. White cell differentials of liver FNABs and simultaneously taken blood samples were performed, and the increment and corrected increment methods were used to quantitate the inflammatory reaction in the liver. Biopsies taken before transplantation were used as the baseline. During aGVHD, the percentage of lymphoid cells and monocytes increased in the liver. The appearance of immunological blasts, together with a high proportion of activated lymphocytes in the FNABs, were typical findings during aGVHD. In patients with apparent prolonged liver graft-versus-host disease small lymphocytes were the predominating cell type. After initiating corticosteroid treatment, the number of blasts and the proportion of activated lymphocytes decreased. There was no significant difference in the proportions of CD4- and CD8-positive lymphoid cells in FNABs during or after aGVHD. PMID- 2595787 TI - Proteins of the respiratory tract after heart-lung transplantation. AB - Heart-lung transplant recipients represent a unique population who experience episodic lung injury caused by infection or rejection. We hypothesized that the proteins in the respiratory lining fluids of these patients might reflect and provide insights into the in vivo immunologic and inflammatory events that occur in the transplanted lung. Structural, inflammatory, and immune proteins were quantitated in 57 samples of BAL fluid recovered from 17 heart-lung recipients when infections, rejection, or neither was present. Protein levels were compared with those of normal subjects and between the clinical transplant groups. When neither infection nor rejection was present, levels of albumin, fibronectin, and immunoglobulins G, M, and A were all higher in the transplanted lungs as compared with the normal lungs. These findings suggest that a new steady state of these proteins is established in the transplanted lungs. When infection or rejection was present, there was a further significant increase in albumin, fibronectin, IgG, and especially C5a in the transplanted lungs. These findings suggest that at least some elements of host defense remain intact in the posttransplantation period despite the use of immunosuppressive drugs and a HLA-incompatible microenvironment. The profiles of recovered alveolar proteins did not, however, help to differentiate infection from rejection. This is disappointing because distinguishing between infection and rejection without examination of lung tissue remains an unresolved and important clinical problem. Nevertheless these data provide new insights into organ tolerance and defense of the newly transplanted lung from infection or rejection. PMID- 2595788 TI - Pancreatic juice cytology in the monitoring of pancreas allografts. AB - A technique for preparation of pancreatic juice for cytological examination, which was applied in 35 consecutive recipients of a pancreas allograft, is described. Pancreatic juice cytology (PJC) was performed daily, giving a total of 1116 cytological specimens. In these 35 pancreas grafts, 26 acute cellular and two vascular rejections were diagnosed on the basis of exocrine and endocrine graft function, perfusion scans, and clinical course and outcome, and were retrospectively compared with PJC findings. Histology was available only for vascular-type rejections. In uncomplicated cases, mainly neutrophil granulocytes with some ductal epithelial cells and 2-3% lymphocytes were seen. During 96% of acute cellular rejections an increase of lymphocytes was detected to more than 5% of all cells counted. In two-thirds of these episodes, eosinophil granulocytes and/or necrotic epithelial cells were found. The total number of cells was significantly increased in 60% of the cases. A minimum of two of these criteria was necessary for diagnosis of rejection. Rejections were correctly diagnosed in 234 slides (23 episodes) and missed in 36 (three episodes), PJC gave a false positive result in 27 examinations (three rejections), but a correct negative result in the remaining 819 examinations. This gives a sensitivity of 86.6% and a specificity of 96.8%. With the exception of viral pancreatitis, where no specific changes were seen, PJC also proved very helpful in diagnosing other complications after pancreas transplantation, such as pancreatitis, bacterial or fungal contamination of the juice, and even cyclosporine toxicity. PJC facilitated the detection of isolated rejection episodes of the pancreas graft in recipients of a combined renal pancreatic graft, which happened in six instances. PJC has proved to be a simple but most helpful method for the detection of cellular rejection of pancreas allografts, as well as other complications. PMID- 2595790 TI - Bile cytology in orthotopic liver transplantation. AB - The utility of bile cytology (BC) in the diagnosis of hepatic graft rejection was assessed in 21 liver transplantations in 18 patients. A total of 307 BC specimens were studied; cell density and relative contribution of different cell types were monitored in 130 specimens. The findings in 62 fine-needle aspiration biopsies and 9 core needle biopsies (CNB) from the transplants were compared with those of the BC specimens. For the first 3-5 days after transplantation, BC specimens were cell-rich, containing degenerating cells and polymorphonuclear leukocytes. In uneventful cases, the cellularity of the specimens gradually decreased. Upon rejection, the number of cells increased, with a high percentage of PMN. Occasionally, blasts or macrophages were detected. After antirejection treatment, the cellularity of the specimens decreased. The analysis of the relationship between the findings of BC and FNAB showed that a high cell density was indicative of rejection. However, BC was not as sensitive to rejection as was FNAB. No clear-cut correlation was found between BC pattern and the degree of cell infiltration in portal triads as seen in CNB specimens. Our results indicate that serial bile cytology is valuable as an additional diagnostic method in monitoring hepatic graft rejection. PMID- 2595789 TI - Serum F protein estimation in liver allograft recipients with graft dysfunction. AB - Serum levels of F protein, a 44 kD cytoplasmic protein mainly found in hepatocytes, became elevated during episodes of graft dysfunction following orthotopic liver transplantation. In a study of 27 liver transplant recipients, the rise in F protein did not precede rises in the other conventional biochemical indices of hepatic dysfunction. Serum F protein concentration significantly correlated with serum levels of aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, and bilirubin (all P less than 0.001) and also with the prothrombin time (P = 0.048). Despite its high concentration in liver cells, this marker does not provide any additional benefit in the diagnosis of graft dysfunction or in monitoring liver allograft function following transplantation. PMID- 2595791 TI - Intercellular communication within the liver has clinical implications. PMID- 2595792 TI - Null method or operational model? PMID- 2595794 TI - Anonymity in refereeing. PMID- 2595795 TI - Adenosinergic psychopharmaceuticals? PMID- 2595793 TI - Finding affinity constants for agonists by the irreversible antagonists method. PMID- 2595796 TI - Peripartum cardiac failure. A ten year follow-up study. AB - A cohort of patients with peripartum cardiac failure (PPCF) was followed for 10 years after the initial illness. The follow up rate was 78%. Fifty two per cent of patients improved without further episodes of heart failure. PPCF recurred in 26 per cent. Heart failure unrelated to pregnancy was seen in 13%, and 9% of the patients progressed to dilated cardiomyopathy. Transient hypertension was seen in 87% of patients on admission, and later hypertension was found in 45%. Late hypertension influenced heart size more when recurrent PPCF or progressive heart failure was present. Anaemia on admission had no effect on subsequent heart size. The electrocardiogram may continue to be abnormal for up to 10 years in normotensive patients who had no heart failure. The abnormal electrocardiogram in patients with persistent cardiomegaly may represent progressive myocardial damage. Mortality rate was highest (11%) in the first year and declined thereafter. Cardiac deaths were common in patients with recurrent PPCF or progressive heart failure. PMID- 2595797 TI - Peripartum cardiomyopathy in a rural Nigerian hospital. AB - In a rural hospital in Northern Nigeria in 1985 seventeen patients were admitted who met with the criteria of peripartum cardiomyopathy. Local habits played an important part in the course of the disease. Physical examination with an emphasis on bloodpressure and the condition of the heart was most reliable in establishing the diagnosis and assessing the treatment. Electrocardiography (ECG) was introduced, but proved of low value. Treatment consisted of bedrest and diuretics. One patient died, eight patients made a full clinical recovery but eight patients did not improve. Unfortunately all patients withdrew from follow up. PMID- 2595798 TI - Parasitologic survey of Onchocerca volvulus infection in the Nimiyama Chiefdom, Kono District, Sierra Leone. AB - Infection due to Onchocerca volvulus was investigated in the Nimiyama Chiefdom, Kono District, Sierra Leone, where Simulium damnosum s.l. is known to breed but no data on the prevalence and intensity of O. volvulus infection exists. Of the 735 individuals sampled by the skin snip method in five villages, 471 (64%) were infected. The infection rate for males was significantly (p less than 0.05) higher than that of the females. Two hundred and ninety-one (70.0%) of the 416 males skin snipped and 180 (56.0%) of the 323 of their female cohorts were infected. The intensity of infection increased with age, with the younger cohorts presenting lower microfilarial density (MFD). Palpable nodules were observed in 230 (48.4%) of individuals found positive for skin microfilariae and in 37 (5.0%) individuals found negative for skin microfilariae. It is concluded that O. volvulus infection is mesoendemic in the Nimiyama Chiefdom, with the intensity of infection increasing with age. PMID- 2595799 TI - Chromomycosis: a twenty-year analysis of histologically confirmed cases in Jamaica. AB - Thirty-one cases of histologically confirmed chromomycosis seen at the University Hospital of the West Indies (UHWI) between 1967 and 1986 were reviewed. A mean age of 56 years and a 5 to 1 male to female ratio were recorded. The lower limb was infected most frequently and both the macroscopic and microscopic disease showed typical features. Fonsecaea species were isolated in all 16 cases in whom mycological information was available (14 cases of F. pedrosoi). Surgical excision and split skin grafting produced long term cure in 7 to 10 cases with limited disease. Chromomycosis is more common in Jamaica than previous records would suggest. PMID- 2595800 TI - Choice of intravenous fluid infusion in labour and maternal postpartum blood pressure. AB - The effect of using either normal saline or 5% glucose solution, as fluid vehicle for oxytocin, on postpartum blood pressure was investigated in 138 parturient women. Blood pressure measurements were done at the commencement of infusion, immediately after delivery, at 1 hour and at 12 hours postpartum. There was no significant difference in the mean values of the mean arterial pressures or in the frequency of occurrence of postpartum hypertension between the two groups. PMID- 2595801 TI - Poor acceptance of caesarean section in Zimbabwe. AB - A survey was carried out in a maternity hospital in Gweru, Zimbabwe, in order to analyze the acceptance of Caesarean Section (C.S.). The behaviour of 210 pregnant women who had a previous C.S. was compared with that of a control group of 278 women with no history of C.S. More frequently, the former failed to attend antenatal clinic and came to the maternity hospital in an advanced stage of labour. The majority of them did not wish to have a further C.S. and did not know they were at high risk of complication. These observations have important implications for medical training and public health policy planning in African countries. PMID- 2595802 TI - Plasma magnesium and retinopathy in black African diabetics. AB - Observations in Caucasian diabetics have linked hypomagnesaemia as being an additional risk factor for the development of retinopathy which is a major microvascular complication of diabetes mellitus. We estimated fasting plasma magnesium concentrations in 82 non-insulin-dependent Nigerian diabetics with normal renal function and 48 healthy subjects. The diabetic patients were divided into two subgroups according to the presence (n = 25) or absence (n = 57) of retinopathy. Both diabetic subgroups were comparable regarding their metabolic control, body mass index and duration of diabetes. Hypomagnesaemia was observed in the diabetic patients as a whole and in the diabetic subgroups with and without retinopathy; however these levels were not of statistical significance when compared to healthy controls. Furthermore, when the two diabetic subgroups were compared, no significant differences were observed in the magnesium concentrations. Our data suggests that hypomagnesaemia may not be associated with the occurrence of retinopathy in black African diabetics. PMID- 2595803 TI - Plasma HDL cholesterol, triglyceride and total cholesterol levels in non insulin treated Nigerian diabetics. AB - Total cholesterol, triglyceride and HDL-cholesterol concentrations were measured in 49 non-insulin-treated Nigerian diabetics and 40 healthy controls. Low levels of HDL-cholesterol were observed in the diabetic group (n = 49) and in both male (n = 20) and female (n = 29) diabetics, but these low levels were of significance in female diabetics only (p less than 0.025) and in the diabetic group considered as a whole (p less than 0.05). Significant hypertriglyceridaemia was observed in the diabetic group (p less than 0.005) and in both male (p less than 0.025) and female (p less than 0.05) diabetics. Total cholesterol concentrations were higher in each of the diabetic groups but these differences were not significant. These results suggest that black African diabetic females may represent a high risk group for development of other long term complications of diabetes mellitus and should therefore be monitored. PMID- 2595805 TI - Blood coagulation changes in liver disease. AB - The study describes the results of prothrombin time (PT), Anti-thrombin III (AT III) and fibrin polymerization curve (FPC) measured simultaneously in patients with liver disease who were divided into two groups: cirrhotics (n = 37) and miscellaneous liver disease (n = 35). There was significant prolongation of PT in 82% of cirrhotics and in 17% of the miscellaneous liver disease group. In contrast significant reduction of AT III levels was noted in 94% of cirrhotics and 31% of the miscellaneous liver disease group. Abnormal FPC was seen in 88% and 32% respectively. There was a good correlation between PT and AT III levels. It was concluded that AT III measurement is a more sensitive indicator than PT and FPC in the assessment of hepatocellular dysfunction. PMID- 2595804 TI - A clinical profile of patients with coronary artery disease in Nigeria. AB - Observations are reported on 31 patients with coronary artery disease (CAD) from Nigeria (a region where CAD is rare). Hypertension either alone (12 cases), or associated with diabetes mellitus and obesity (4 cases), with diabetes mellitus and heavy cigarette smoking (1 case) was a frequent associated illness. Serum cholesterol measured in 15 cases was high in 13, but nine others without cholesterol assay were in the high socio-economic group, and serum cholesterol was likely to be relatively elevated in them also. Hyper-cholesterolaemia was the one factor that Nigerian patients with CAD had, but which is rare in the Nigerian general population. This observation appears to support the view that other major pre-disposing factors to CAD cause this disease usually when there is a back ground of hyperlipidaemia. PMID- 2595806 TI - The emergence of colonic diverticulosis in urbanised Indians. A report of 23 cases. AB - Of a total of 969 barium enemas performed over a three year period, 23 (2.4%) showed colonic diverticulosis. The mean age of the patients was 58 years and the commonest site involved was the sigmoid colon. All the patients were urbanised and were obligatory vegetarians. Six (25%) of the patients had a complication of the disease and three of them required surgery. The possible relationship of the disease with socio-economic changes is highlighted. PMID- 2595807 TI - Intravenous urographic findings in Burkitt's lymphoma. AB - Intravenous urography was performed in 13 patients with Burkitt's lymphoma and showed that 4 cases had bilateral diffuse renal lymphomatous deposits. Back pressure changes due to ureteric compression by abdominal or pelvic masses was recorded in 5 cases and lateral displacement of the ureter in 3 cases. One patient showed bilateral poor excretion of contrast medium while 2 cases had extrinsic impressions on the urinary bladder. Intravenous urography was helpful in determining the extent of urinary tract involvement in Burkitt's lymphoma and serves as an important diagnostic tool in the investigation of patients with urinary tract symptoms or signs in this disease. PMID- 2595808 TI - The epidemiology of paraquat intoxications in Surinam. AB - The epidemiology of paraquat (PQ) intoxications in Surinam was studied in the Akademisch Ziekenhuis Paramaribo, the University Hospital that manages 83% of all cases occurring throughout the country. For 1985 and 1986 the corrected incidence rates of PQ poisoning were 211 and 68 cases/million population/year. The former is the highest figure reported worldwide. Incidence was more pronounced in males than in females, and 30-39 years males had the most extreme age specific rate. Suicide attempts accounted for 76% of our cases. Hindustani, who have easier access to the product, were at higher risk than other ethnic groups. The overall case fatality rate (CFR) was 71%. It was significantly more unfavourable in males (79%) than in females (57%) and increased with age. CFR was not related to circumstance of poisoning or ethnicity. The monthly incidence of PQ poisoning depended on the volume of monthly PQ imports and the year under study. The latter may be explained by qualitative changes in the distribution system in 1986 when, for economic reasons, the product was only sparsely available to the general public. This observation lends strong support to the WHO recommendation to restrict supply of PQ concentrate to professional users. PMID- 2595809 TI - Cestode larva (Sparganum) in the anterior chamber of the eye. AB - The first case of intraocular sparganosis presenting as endophthalmitis is reported with a live plerocercoid larva of Spirometra lodged in the anterior chamber of the eye of a man in India. The larva was identified histologically. PMID- 2595810 TI - Tuberculosis presenting as corticosteroid responsive wheezing in infancy. AB - A nine-month-old child received intermittent oral prednisolone over a 6 month period because of persistent wheezing. This therapy had appeared to improve his symptoms. At 15 months of age, a chest X-ray and culture of tracheal aspirate revealed disseminated pulmonary tuberculosis. Response to antituberculous therapy was slow, and withdrawal of steroids produced marked worsening of wheeze and respiratory distress. Corticosteroids are recognised adjuncts in the management of bronchial-lymph node tuberculosis. Responsiveness of wheezing to prednisolone does not imply that its cause is hyperreactive airways disease, and other causes should be sought particularly in developing countries. PMID- 2595811 TI - Rhinosporidiosis in a Nigerian. AB - A case of rhinosporidiosis in a Hausa man from northern Nigeria is reported. This apparently constitutes the first case recorded from Nigeria. PMID- 2595812 TI - Werdnig-Hoffmann disease in a Nigerian infant. AB - A Nigerian infant with the classical features of Werdnig-Hoffmann disease is described. According to the literature the incidence in black Africans is very low. Attention is drawn to the fact that neurological illnesses are often overlooked in negroid races; several reasons are given. PMID- 2595814 TI - [Doppler ultrasound--anatomy correlations in 45 cases of infectious endocarditis]. PMID- 2595815 TI - [Rupture of congenital aneurysms of the sinus of Valsalva]. PMID- 2595813 TI - [Chromosome aberrations in hothouse workers coming in contact with pesticides]. AB - The frequency of chromosome mutations in the peripheral blood lymphocytes has been studied in 40 greenhouse workers professionally contacting with a complex of pesticides. The frequency of chromosome aberrations in the group of workers amounts to 6.0 +/- 0.3%, that is higher than the frequency of aberrations in the control group. PMID- 2595816 TI - [Complete and old complicated perineal lacerations of obstetric origin: apropos of 22 cases]. PMID- 2595817 TI - [Value of bronchoalveolar lavage in rheumatoid polyarthritis: apropos of 16 cases]. PMID- 2595818 TI - [Organized detection of hereditary metabolic diseases. Amino acidopathies and organic acidurias]. PMID- 2595819 TI - [Prevention of human rabies in Sfax]. PMID- 2595820 TI - [Ectopic junction of the ureter: a rare cause of urinary incontinence]. PMID- 2595821 TI - [Association of a triple artery and acute cerebrovascular attack with hemolytic anemia in a 4-year-old child]. PMID- 2595822 TI - [Localized pulmonary amylosis: apropos of a case]. PMID- 2595823 TI - [Myasthenia and Basedow's hyperthyroidism: apropos of a case]. PMID- 2595824 TI - [Intestinal cryptosporidiosis in AIDS: apropos of a case]. PMID- 2595825 TI - [Nocturnal enuresis--new treatment principles in the light of increased understanding of the physiopathology]. PMID- 2595826 TI - [Eye care in Greenland in 1979-1988]. AB - Specialist eye care in Greenland is described on the basis of 66 reports from all 30 visiting consultants during a ten-year period. During this time the durations of the visits increased to approximately seven months per year for 8-9 ophthalmologists who undertook approximately 2,500 consultations annually. The diagnoses were distributed as follows: 30% anomalies of refraction, 15% cataract, 12% conditions in the posterior segment and 10% glaucoma, i.e. a considerable proportion of eye diseases associated with advancing age and with a particular Greenlandic influence. The workload was particularly great and averaged more than a reasonable weekly load despite the increase in number of days of employment. Until 1985-1986, eye surgery activities showed a considerable increase after which operative interventions for cataract and glaucoma were mainly referred to Rigshospitalet. The great increase in the number of referrals is discussed in relation to the marked changes in the therapeutic possibilities for cataract and glaucoma: extracapsular cataract extraction with posterior chamber implantation using an operation microscope and YAG-laser iridectomy of early angle closure glaucoma. The requirement of an eye surgical unit in Greenland appears to be pressing together with continuation of specialist eye care in the districts. PMID- 2595827 TI - [Sexual behavior in HIV antibody positive homosexual and bisexual men]. AB - With the object of describing how their own health is experienced, the social circumstances and sexual behaviour in anti-HIV-positive homosexual and bisexual men, an anonymous questionnaire to be completed by the recipient was distributed in 1987 in connection with a placebo controlled investigation to assess the value of isoprinosin (Imunovir) in preventing the development of AIDS. 87% participated. Among the total of 85 participants, 78% considered that their health was good, 29% met family members and 75% friends at least once weekly. Fifty patients (65%) felt stressed in their daily lives which was definitely higher than in the normal population. All of the participants had altered their sexual behaviour in a manner which reduced the risk of HIV-transmission but 18 (21%) had had sexual behaviour known to transmit HIV within the past year. This behaviour occurred more frequently in young persons (p = 0.09) and in smokers (p = 0.03). In addition, no connection could be demonstrated between a series of possible determinants for this, which may, however, be due to the limited extent of the material. It is demonstrated that awareness that one is infected with HIV does not eliminate dangerous sexual behaviour in all cases. PMID- 2595828 TI - [Blood pressure screening in the present health service]. AB - By means of an interview investigation of a representative random sample of the adult Danish population of 16 years and more and comprising a total of 4,753 persons, blood pressure screening in the present Danish health service is illustrated. 6.7% stated that their blood pressure had never been measured. 48.3% had had blood pressure measurements within the past year and 71.4% had had blood pressure measurements within the past three years. The proportion of blood pressure measurements was significantly more frequent in men than in women and was greatest in the age group 16-24 years. 6.5% of those who stated that they had raised blood pressure had not had blood pressure measurements within the past year and this proportion was greatest among patients who did not receive medicinal treatment than those receiving medicinal treatment for raised blood pressure. Fewer risk factors for raised blood pressure were found among persons without blood pressure measurements than among others. 3.7% of those who had been in contact with their general practitioner within the past three months had never had their blood pressures measured. A number of suggestions are made to improve tracing of persons with raised blood pressures in the primary health service. PMID- 2595829 TI - [Monitoring routines at Danish anesthesia departments]. AB - By means of a questionnaire investigation, 84 Danish anaesthetic departments were questioned in January 1987 about their monitoring routines during anaesthesia and recovery. 100% replied. The investigation revealed that measurement of the blood pressure in adults was the routine in all of the departments. Patients were monitored routinely with EGG in 62 departments where minor surgical interventions were concerned while, in major surgical intervention, ECG monitoring was the routine in 91% of the departments. Patients were observed postoperatively in the recovery room or intensive care unit in 51% of the departments. The questionnaire investigation revealed great variation in the monitoring and supervision routines in the anaesthetic departments in Denmark. Hitherto, it has not been possible to demonstrate that monitoring of the functions of vital organs in operation patients can reduce the morbidity and mortality connected with the anaesthesia. It is concluded that it would be desirable to carry out clinically controlled investigations to illustrate whether monitoring equipment can reduce the morbidity connected with anaesthesia and to develop a Danish recommendation concerning peroperative monitoring and postoperative observation. PMID- 2595830 TI - [Treatment principles in urethral stricture in Denmark. A questionnaire study]. AB - A questionnaire presented to 79 danish surgical departments showed that about 2,000 urethral strictures are treated in Denmark per annum. These were mainly incised by Sachse's method. 8% of the patients do not have postoperative catheterisation, while the remainder have indwelling catheter from 1-28 days, mainly between 1-3 days. The reasons for the chosen regimes are presented. PMID- 2595831 TI - [Intracranial meningioma. Results and social prognosis after surgical treatment]. AB - During the period 1976-1984, intracranial meningomata (ICM) were diagnosed in 69 women and 22 men aged 24-83 years. Epileptic manifestations of up to ten years duration and focal neurological signs were thrice as frequent as signs of increased intracranial pressure. Radical removal of the intracranial meningioma was performed in 67 cases, partial resection in 15, biopsy of the tumour in one patient and a shunt-operation was performed in one patient. In one of the patients, the tumour was malignant. Three patients were submitted to irradiation. The neurological condition underwent temporary deterioration and 1/6 and permanent deterioration in a further 1/6. Eleven of the patients had postoperative complications (haematomata and infections) and there were two deaths during the immediate postoperative period. After an average follow-up period of 7 1/2 years, 27 further patients had died. In 3/5 of the survivors, the social conditions and the working ability were unchanged as compared with the preoperative status and these conditions were poorer in the remaining survivors. Recurrence of the intracranial meningeomata had occurred in four patients. PMID- 2595832 TI - [The pattern of riding injuries]. AB - During the period from 1.1. to 31.12.1988, 104 patients with injuries resulting from riding or other forms of direct contact with horses were examined and treated in a casualty department in the County of Vejle. Antecedent data from these patients were collected. The majority of injuries occurred on falling from the horse and involved particularly the upper part of the body. The commonest injuries were bruises which did not require special treatment. The relationships between concussion, fracture of the humerus and fracture of the clavicle and riding were investigated by odds ratio. Much fewer serious injuries than anticipated were found in the present investigation and this must be considered on the basis of a greater incidence of injuries than in other investigations. The iatrotropic threshold thus causes a certain selection bias. PMID- 2595833 TI - [Hand injuries caused by hydraulic wood-splitting machines]. AB - Five cases of hand lesions caused by hydraulic wood-splitting machines are described. Prophylactic measures are discussed. PMID- 2595834 TI - [Disease patterns in patients hospitalized in 1987]. PMID- 2595835 TI - [The rotator cuff syndrome]. PMID- 2595837 TI - [Nose neoplasms and paranasal sinus neoplasms]. PMID- 2595836 TI - [Diabetes insipidus]. PMID- 2595838 TI - [DDAVP (1-desamino-8-D-arginine vasopressin )]. PMID- 2595839 TI - [Children's life conditions must be improved]. PMID- 2595840 TI - [Life conditions of families with children in the Municipality of Copenhagen. 1. A description based on registered data]. AB - By means of combining data from various registers concerning the population in the Municipality of Copenhagen, the living conditions for families with children are described. More than one third of the 36,063 families with children in Copenhagen have only one bread-winner. The older the children are, the more often they live with only one of their parents. Families are small and one third of the children are only children. Many of the families with children have poor housing conditions and just under one fourth have no bath. Many families have a low income and just under one third have a total income of less than 150,000 Danish crowns annually (12,500 pounds). In general, families with low incomes live under poorer conditions than the other families and similarly, the children are hospitalized more frequently than the remaining children. Families with one bread winner are frequently stressed by low incomes and the children are hospitalized more frequently than the remaining children. Immigrants have poor housing conditions and have very low incomes. The Children's Commission's conclusions concerning the living conditions of families with children are discussed in the light of this investigation. PMID- 2595841 TI - [Life conditions of families with children in the Municipality of Copenhagen. 2. Life conditions distributed in social districts]. AB - As the basic knowledge for possible health planning in smaller districts, a description was made of the basic living conditions of families with children in Copenhagen and the utilization of public assistance and the employment of hospitalization of the children. These parameters are distributed among the 20 social districts in the municipality. The material concerning the more than 36,000 families was obtained by means of combination of data from registers concerning the population of Copenhagen. Four indicators were chosen for the living conditions of the families with children and by means of an additive index the social districts were ranged as good/poor as regards stressed families with children. Considerable variation was shown between the districts. A markedly positive connection was found between the living condition index of a district and cash public assistance. The living condition index was less clearly associated with the frequencies of hospitalization of the children. Utilization of existing registers in district planning is discussed. PMID- 2595842 TI - [Utilization of medical services for children in an area of Copenhagen]. AB - As part of the development of models for community services for children, the utilization of the medical services for children in a local area in Copenhagen viz the catchment region of the Osterbro Social Centre was reviewed. By means of contact investigations in the above mentioned region with the general practitioners and duty roster doctors in two selected weeks and by information from the Casualty Department Register in the University Hospital and from the National Danish Patient Register, the pattern of illness for children aged 0-14 years and utilization of medical services in the year 1986 was described. Utilization of casualty departments was uniform throughout childhood. In the course of one year, every third child, on an average, had had contact with a casualty department. This is in contrast with other sections of medical services where utilization decreases with increasing age of the child. The frequency of admission to hospital was high, particularly for the youngest children. The majority of all contacts were on account of infectious diseases. A community, multidisciplinary effort to reduce ill health is suggested to combat the many illnesses due to infection, the numerous contacts with doctors and hospital admission. Choice of doctor in cases of acute illness in children is discussed. PMID- 2595843 TI - [Characteristics of first-time blood donors and their motives. A prospective study among voluntary and unpaid blood donors]. AB - We performed a questionnaire study among 413 consecutive voluntary unpaid blood donors being bled for the first time. About 50% were aged below 26 years, 93% were employed or students, and 50% of the donors came from families with other blood donors. The motives to donate blood were investigated. As motives we found: altruistic and humanitarian reasons in about 98%, to obtain a greater well-being in about 60%, tradition at the place of employment or in the family about 35% each. The importance of blood tests taken in connection with the blood letting was analysed. We could not find any support for the hypothesis that blood donors in Denmark enroll as donors to be tested for HIV antibodies. PMID- 2595844 TI - [Chlamydia trachomatis in at-risk groups in legal abortion in the first trimester]. AB - Examination for the presence of C. Trachomatis in the cervix and urethra and bacteriological examination of the cervix were performed in a material of 224 patients for legal abortion in the first trimester of pregnancy. Chlamydia was demonstrated in 8.9% of the patients, Neisseria gonorrhoeae in 0.5% and, in 41%, growth of Gardnerella vaginalis predominated. It proved possible to define a group at risk for the presence of Chlamydia consisting of all the patients under the age of 25 years and nulliparae aged 25-29 years. 17% in this group had positive Chlamydia tests as compared with 1.7% in the patients in other groups. Patients in the above mentioned risk group should be examined for C. trachomatis in cases of legal termination of pregnancy so that appropriate treatment can be administered prior to evacuation. PMID- 2595845 TI - [Gastric banding]. AB - Twenty-three patients with a mean preoperative weight of 126 kg (100-163) and a mean preoperative Broca index of 1.89 (1.54-2.47) were submitted to gastric banding on account of severe obesity. The operative procedure, complications and results are described. The mean period of observation was 12 months (3/4-42). The mean weight loss after 12 months was 28.5 kg. The greatest weight loss per unit of time occurred during the first six months. In the majority of patients, the weight became stabilized after 12-24 months. Two patients did not lose weight and these were regarded as treatment failures. One patient died three weeks after the primary operation on account of infectious complications of pouch-perforation. Apart from this, no serious complications occurred. The incidence of wound infection was 17%, development of herniae in the scars occurred in 35% and transient symptoms of functional stenosis were encountered in 35%. Despite the high incidence of less serious complications, the authors consider that gastric banding is an employable alternative to intestinal and gastric bypass operations. In future, we will consider perioperative antibiotic therapy although gastric banding is, in principle, a clean operation. In addition, we will reserve gastric banding for patients who do not consume the majority of their calories in fluid form. PMID- 2595846 TI - [Stress fracture of the femoral neck in a young long-distance runner]. AB - A case of stress fracture of the femoral neck in a 19 year-old runner is presented, followed by some general considerations on stress fractures, with special reference to runners. PMID- 2595847 TI - [Interpleural bupivacaine (Marcain) in the treatment of pain in a patient with chronic pancreatitis]. AB - A case of long-term relief of pain after interpleural blockade with bupivacaine in a patient suffering from severe chronic pancreatitis is reported. PMID- 2595848 TI - [Have ACE antagonists disclosed the existence of complicated and fully developed forms of essential hypertension?]. PMID- 2595849 TI - [Acute appendicitis in pregnancy]. PMID- 2595850 TI - [Complications of appendectomy during pregnancy]. AB - A retrospective investigation revealed that in 11 out of 23 pregnant women submitted to operation on account of suspected appendicitis the diagnosis could be confirmed. The perinatal and the maternal mortalities were both 0. In the women submitted to operation, the frequency of obstetric complications was found to be 17%, 95% confidence limits 5-39%, and the frequency of surgical complications was 17%, 95% confidence limits 5-39%. The diagnostic specificity was found to be significantly higher in women who had previously born children. Brief duration of symptoms preoperatively and operation employing beta sympathomimetics are recommended. PMID- 2595851 TI - [Fiber bronchoscopy and bronchoalveolar lavage in patients with asthma. A description of the method]. AB - Fiber bronchoscopy under local anaesthesia is an examination procedure frequently employed in the remainder of Scandinavia, Europe and USA. It requires only few resources and the costs are considerably less than fiber bronchoscopy under general anaesthesia. Bronchoalveolar lavage (BAL) in connection with fiber bronchoscopy is rapidly undertaken but analysis of the material obtained requires considerable time. A method of induction of local anaesthesia, performance of BAL and preparation of the washings obtained is described. Fiber bronchoscopy and BAL are considered to be safe examination procedures in patients with mild asthma in a stable phase. The examination is only associated with slight discomfort for the patients, who will frequently accept repeated investigations, and complications are rare. BAL is a valuable examination procedure in research and the results have increased the knowledge of mechanisms in a series of interstitial pulmonary diseases. Future investigations of the humoral and cellular components in BAL fluid in asthmatic patients will contribute to increase knowledge of the pathological mechanisms in asthmatic disease. PMID- 2595852 TI - [The disease course in patients admitted to a rehabilitation department following spinal cord injuries]. AB - Epidemiologic data from 109 patients admitted to hospital in the period 1/1/1980 /31/12/1984 with spinal cord injuries are presented. The mean age was 29 years, there was a preponderance of males and the most frequent cause of the spinal cord injury was road accidents. The material was compared with the epidemiologic and social data of other studies. A total of 58 patients, chiefly users of wheelchairs, were followed up on average six years after the first admission. It was thus possible to form an idea of the complications of the spinal cord injury and the effectiveness of the treatment. The premorbid educational level of the patients was relatively low. The most frequent complications were spasms (74%), pressure sores (67%), pains (58%), and frequent urinary tract infections (71%). The consumption of medicine reflected the pattern of complications. The most common method of micturition was reflex voiding by tapping. These results were comparable with previous studies. It is concluded that the treatment of spinal cord injuries is a specialised task and only continuous evaluation can ensure optimum treatment. PMID- 2595853 TI - [Late episodic hypoxemia and variation in heart rate following major abdominal surgery]. AB - In thirteen patients who were submitted to elective major abdominal surgery, the heart rate and arterial oxygen saturation were monitored continuously on the preoperative night-to-day prior to operation and the first and second postoperative nights (from 11 pm till 7.30 am). The heart rate increased by an average of approximately 22 beats/minute (p less than 0.005) and the oxygen saturation decreased approximately 4.5% (median) (p less than 0.003) after the operation. During the second postoperative night, two patients had 120 and 372 episodes respectively of sudden decrease in saturation to less than 80%. On the morning of the third day, the second of these patients developed cardiac arrhythmia requiring treatment. In one of these patients, the episodes were closely correlated with increase in the heart rate. No connection was observed between administration of opiates and disturbances in oxygen saturation or heart rate. The clinical relevance of episodic decrease in saturation in the late postoperative phase is still unknown but may be of significance for the development of cardiac and cerebral dysfunctions. PMID- 2595854 TI - [Herpes zoster in immunosuppressed patients with immuno-inflammatory disease]. AB - We analysed 19 episodes of herpes zoster in 16 patients, who received cytotoxic drugs or cyclosporin for immuno-inflammatory disease. Reactivation of varicella zoster virus was not associated with increased activity of the rheumatic disease nor with increased intensity of immunosuppressive therapy. Six of the patients who had received the largest cumulative doses of cytotoxic drugs had fever and/or vesicles outside the primarily affected dermatome. Two of these patients developed post-herpetic neuralgia. Although not encountered in this material, immunocompromised patients may develop severe complications of herpes zoster, and therefore prompt treatment with acyclovir is recommended in all cases. It is suggested that oral acyclovir therapy is sufficient in uncomplicated cases but this question has not been elucidated in controlled studies. PMID- 2595855 TI - [Diagnostic reliability of the CLA test and RAST in IgE-mediated allergy compared with anamnesis and the prick test]. AB - The principle and mode of conduction of a non-isotope method, the DHS-CLA-allergy test, for in vitro diagnosis of allergic disease is described. The method has been tested and found easy to carry out without special laboratory facilities. Thirty-nine patients all of whom were suspected of allergy were tested for nine typical allergens with the prick test, Al-RAST (ALK) and the DHS-CLA-allergy test. Definite allergy was defined on the basis of definite history of allergy and the positive prick test and, from this, the nosological sensitivity was calculated. No history of allergy and negative prick test results were defined as no allergy, and the nosological specificity was calculated from this. The nosological sensitivity for all nine allergens: Al-RAST: 46.8%, DHS-CLA: 85.5%. Nosological specificity for all nine allergens: Al-RAST: 85.7%, DHS-CLA: 80.3%. The results for the individual allergens are apparent from the text. PMID- 2595856 TI - [18 children with slight glomerular proteinuria demonstrated incidentally]. AB - Out of 61 children with idiopathic chronic glomerulonephritis confirmed by biopsy or minimal lesion diagnosed during the period 1964-1987, 18 were found in whom the first sign of renal disease was slight proteinuria demonstrated at routine examination of the urine. Five of these children were referred directly to a nephrological department with the object of further elucidation of the diagnosis. In six of the remaining 13 children, the first referral to hospital took place after an average of 5.9 years and after signs of renal disease were apparent for the first time. In ten of these 13 patients, an average period of 3.9 years elapsed before renal biopsy was carried out and the nature of the disease elucidated. 29 and 73% of these patients, respectively, had developed terminal uraemia five and ten years after establishing the diagnosis. It is recommended that children in whom persistent proteinuria is demonstrated, regardless of the magnitude, should be referred directly to a nephrological department or a paediatric department with special interests. Renal biopsy may be indicated. Life long systematic follow-up control is indicated. PMID- 2595857 TI - [Status report on allergen immunotherapy (hyposensitisation). Prepared by the WHO/IUIS Immunotherapy Subcommittee 1988]. PMID- 2595858 TI - [Accidental poisoning]. PMID- 2595859 TI - [Ways to reduce disability as a consequence of urologic diseases]. AB - Analysis of the disability pattern associated with urological diseases revealed that the patient's capacity for work depended rather on the nature of the lesion in the kidney or urinary tract (uni- or bilateral involvement or the involvement of a sole kidney) than on the nosological entity. The reasons of low rehabilitation levels could be explained by a late diagnosis, insufficient conservative or operational treatment, low qualification of labor examination committee and the defects of a dispensary follow-up. The authors defined the main criteria for the assessment of urologic patient's capacity for work and, on their basis, developed a mathematical simulation model for disability and techniques for individual approach in the prognosis for the labor capacity. The ways to raise the efficacy of rehabilitation measures were defined as well. PMID- 2595860 TI - [Immunocorrective therapy of pyelonephritis in children]. AB - A total of 40 children who suffered from acute or chronic pyelonephritis underwent immunological treatment with polypeptide drug tactivin. There was an evidence of clinical and laboratory improvement in 82.5 per cent of treated persons, first manifest in decreased proteinuria and normalized urinary sedimentation, and then in lower levels of bacteriuria due to the developing resistance to infectious agents. In 15 per cent of tactivin-treated children leukocyturia persisted though the disease progression was hindered. In the course of the treatment no side-effects were noted. In line with the stimulation of humoral immune response and activation of the complement system, tactivin administration evoked the competence of T-lymphocytes and potentiated the development of this link of immune system. As part of combined treatment the above preparation favourably affected the disease pathogenesis in children. PMID- 2595861 TI - [Are the sequelae predictable for sectional and multiple partial nephrolithotomies of completely intrarenal coral stones? (experimental and clinical research)]. AB - In the assessment of surgical intervention for fully intrarenal stone casts, different kinds of nephrotomies (sectional or multiple partial ones, those supplementing pyelolithotomy or performed in the kidneys with marked parenchyma) should be compared in terms of functional outcomes, severity and incidence of complications (intraoperative or postoperative bleeding from the violated kidney), postoperative urinary fistulas, aggravated renal failure and postoperative mortality. It is these milestones that have determined the scope of the present study. An experimental assessment of the degree of trauma, associated with sectional nephrolithotomy as well as its functional sequelae was made in dogs after a stone-like structure was simulated and the kidney reached the necessary degree of secretory deficiency. The comparison of pre- and postoperative renographic parameters over different spans of follow-up of animals after sectional nephrolithotomy was made to assess the latter's organ-damaging effect and, in part, functional results of surgery in a kidney with a profound functional deficiency by the time of the operation. A similar methodology was used in clinical patients, subjected to nephrolithotomy (either sectional or multiple partial procedure) for fully intrarenal coral stones. Functional results of nephrolithotomies in animals and in patients are presented in Figs 1-3. For cases where postoperative results were good or satisfactory at 1-2 months, follow up results are presented in Tables 4-5. Postoperative complications of sectional and partial nephrolithotomies are reflected in Figs. 4-5. The incidence of paranephritis and postoperative mortality are reported in Tables 6-7. Therefore, functional results of sectional nephrolithotomy are indicative of its considerable organ-sparing effect in experimental animals. Functional outcomes of the clinical sectional and multiple partial nephrolithotomies are similar, yet partial nephrolithotomies are more detrimental to the kidney and the upper urinary tract in terms of the pattern and rate of postoperative complications, as compared to sectional nephrolithotomy. As the sequelae of sectional and partial nephrolithotomies are largely unpredictable, indications for surgical removal of intrarenal stereometrically-composite coral stones should be as limited as possible. PMID- 2595862 TI - [The role of prolactin in the pathogenesis of male sterility]. AB - To study the causal relationship between the hormonal status and spermatographic data in sterile males, the authors investigated the correlations between the plasma levels of testosterone, estradiol, prolactin and gonadotrophin and certain parameters of spermograms and computed the correlative relationship of those values. The findings demonstrated the increased levels of prolactin (249.09 +/- 39.6 mu/U/ml), significantly exceeding the normal (132.6 +/- 32.4 mu/U/ml), a tendency towards a decrease in the levels of FSH and testosterone (up to 7.01 +/- 0.70 nmol/l versus 12.57 +/- 0.39 nmol/l in health) and manifest elevation of estradiol levels (up to 634.71 +/- 29.16 nmol/l versus 205.02 +/- 18.60 nmol/l), as well as its ratio to the testosterone levels. The number of spermatozoa in 1 ml was found decreased up to 29.6 +/- 4.10 million, the volume of ejaculate was reduced to 2.7 +/- 0.41 ml, while the percentage of immobile spermatozoa rose to 40.00 +/- 4.76. Despite of some pathological changes evidenced by spermograms, there was the only parameter--the volume of ejaculate--that was directly dependent on the levels of prolactin, their correlation was reversed. Decreased numbers of spermatozoa and their motility were not related to hyperprolactinemia. Moreover, there was a positive correlation between the levels of prolactin and the motility of spermatozoa in sterile patients. Therefore, decreased number and motility of spermatozoa turned to be dependent not on prolactin but sex hormone levels. However, ejaculation was found unfeasible in male with high levels of hyperprolactinemia. PMID- 2595863 TI - [The use of BCG vaccine in the treatment of surface tumors of the bladder]. AB - The paper presented results of the treatment of 110 patients with vesical surface tumors, 85 of them were postoperatively treated according to the regime suggested by Adolphs and Bastian and slightly modified for patients with relapsing vesical tumors. For the therapeutic or preventive effect (after TUR or transvesical electrical resection of the urinary bladder surface tumors), the authors used for 6 weeks after the operation intravesical instillations of BCG vaccine ("Calgevax", Bulgarian production) in a weekly dose of 120 mg per 50 ml of the serum. Previously, for this purpose intravenous injections of cyclophosphamide had been routinely used in a dose of 700 mg/m2 during 2 postsurgery weeks. Intracutaneous vaccinations were performed simultaneously. The follow-up which lasted from 18 to 48 months revealed tumor relapses only in 26 per cent of those under study. The patients with relapses were repeatedly operated on, but their postsurgical management was modified: 2 intravesical instillations of 120 mg of BCG vaccine during the first month after the surgery and then monthly instillations of the same dosages for the whole of the year followed. A subsequent 14-26-month follow-up revealed no relapse of the tumors. The authors concluded that the use of BCG vaccine was a practicable part of the combined treatment of patients with vesical surface tumors. PMID- 2595865 TI - [Reasons for the late diagnosis of Reiter's disease]. AB - The main causes of the delay in reaching the appropriate diagnosis of Reiter's disease were analysed. It was concluded that even if the only sign from the disease symptomatic triad (mainly slowly progressing nonspecific urethritis or prostatitis) was observed, Reiter's disease should be suspected and its verification include immunological techniques. Tetracycline antibiotics were found to be mandatory indicated as an etiotropic treatment. PMID- 2595864 TI - [Hemodialysis with the use of unilateral catheterization of the subclavian veins in the treatment of acute kidney failure]. AB - The study enrolled 19 patients with acute renal failure (ARF) who underwent 108 sessions of hemodialysis, 2 ultrafiltrations and 1 plasmapheresis. Hemodialysis was performed through the unilateral puncturing of the subclavian vein (which averaged 225 days) by a routine catheter (1.2 mm in diameter) introduced into the vein for the period from 1 to 38 days (13.41 +/- 2.06 days). There was no evidence of complications induced by catheterization. The authors regarded the aforementioned vascular access used for various methods of extracorporeal detoxication in the ARF patients with an alternate blood intake and retrieval through the subclavian catheter as a reliable, available and convenient technique ensuring a sufficient blood flow and satisfactory tolerance by the patients. PMID- 2595866 TI - [Delayed etiotropic diagnosis of urolithiasis of hyperparathyroid etiology]. PMID- 2595867 TI - [Iatrogenic phlegmon of the pelvis with extensive destruction of the urinary tract]. PMID- 2595868 TI - [Listerial prostatitis]. PMID- 2595869 TI - Effect of low osmolar, ionic and nonionic, contrast media on the cytologic features of exfoliated urothelial cells. AB - The effect of low osmolar, ionic and nonionic, contrast media on the cytologic features of exfoliated urothelial cells were measured in vitro and compared to those induced by standard, high osmolar radiographic contrast media. The low osmolar agents were found to induce no significant adverse effects on the cytologic features of the urothelial cells, whereas the ionic agents clearly distorted certain cytoplasmic and nuclear features. These findings may support the use of low osmolar nonionic agents for retrograde urography if posturographic cytologic studies are contemplated. PMID- 2595870 TI - Angiomyolipoma arising in the renal sinus: a difficult radiologic diagnosis. AB - We report a case of angiomyolipoma (AML) occurring in the renal sinus evaluated by intravenous urography (IVU), renal ultrasound (US), angiography, and computed tomography (CT). Imaging features of this lesion are identical to AMLs elsewhere, but preoperative diagnosis was complicated by the unusual occurrence of the tumor in this location in a patient with abdominal pain. Accurate preoperative diagnosis will allow tumorectomy or conservative management. PMID- 2595871 TI - Adrenal myelolipomas: CT appearance with tiny amounts of fat and punctate calcification. AB - Five cases of myelolipoma of the adrenal are presented which contained only tiny foci of fat along with areas of punctate calcification. This computed tomographic (CT) appearance is less common for this neoplasm and has only been described in three of 26 previously published CT cases of this adrenal tumor. The presence of even tiny amounts of fat in an adrenal mass should alert the radiologist to the probable diagnosis of myelolipoma. Small foci of calcification are also frequently associated. PMID- 2595872 TI - Computed tomography of myelolipoma in the accessory adrenal gland. AB - A case of myelolipoma arising from an accessory adrenal gland is reported. The accessory adrenal gland is a developmental anomaly, recognized often in the periadrenal fatty tissue at post-mortem examination. Myelolipoma of accessory adrenal gland should be considered when a suprarenal fat-containing tumor is seen separately from a normal-shaped adrenal gland. PMID- 2595873 TI - Congenital midureteral obstruction. AB - Congenital midureteral obstruction, caused either by a ureteral valve or stricture, is an exceedingly rare entity. When encountered, it is generally misdiagnosed as either primary megaureter or ureteropelvic junction obstruction, leading to a less than optimal surgical approach. Seven children with midureteral obstruction were seen over the past 17 years. Two of the patients presented with hydronephrosis on prenatal ultrasonography, and five with urinary tract infection. In only three was the diagnosis suspected on intravenous urography and voiding cystourethrography alone. Five of the seven cases had either antegrade or retrograde pyelography, prior to or at the time of their operative procedure, and in four of these a correct diagnosis was made. Notably, in five of the seven cases, recognition of the midureteral lesion prior to the surgical incision allowed the approach to be modified and a more appropriate technique (ureteroureterostomy) to be performed. The etiology of midureteral valve and stricture has been attributed to improper recanalization, insufficient vascular supply, or persistence of ureteral folds. Three of our patients had contralateral renal dysgenesis, suggesting an underlying ureteral bud abnormality. PMID- 2595874 TI - Aneurysm of the dilatation balloon catheter: an unusual complication of percutaneous nephrolithotomy. AB - We present herein a previously unreported complication of an aneurysm developing in a balloon dilatation catheter used to dilate a track prior to percutaneous nephrolithotomy. Direct needle puncture of the balloon was required for removal of the catheter. PMID- 2595876 TI - Giant prostatic fossa with misleading radiographic features. AB - The long-term complication of a perforation of the prostatic capsule during transurethral resection of the prostate is described. Calcifications in a giant prostatic fossa led to initially misleading radiologic findings. PMID- 2595875 TI - Allergic reaction following micturating cystourethrography. AB - Adverse reactions associated with the parenteral use of contrast agents are widely recognized, but reactions to contrast agents used in micturating cystourethrography (MCU) are much less common, although absorption of contrast media through intact bladder mucosa has been documented. A significant adverse reaction to ionic contrast material used for MCU in which neither reflux nor traumatic urethral catheterization could be implicated is presented. This case illustrates that significant reactions can occur during MCU and appropriate resuscitation facilities must be available. In a patient with a history of reaction to IV contrast media, the need for MCU should be reviewed and consideration given to nuclear medicine MCU. If a radiologic MCU is needed, consideration should be given to performing it in the hospital, with nonionic contrast media and steroid premedication. PMID- 2595878 TI - [41st meeting of the German Society of Urology. Freiburg, 4-7 October 1989. Abstracts]. PMID- 2595877 TI - A giant stone in the mullerian duct cyst. AB - Cystic diseases in the male pelvis are uncommon, and stones found in male pelvic cysts are very rare. We report a case of a giant stone found in the male pelvis. Computed tomography was helpful in locating the stone, and surgery revealed it to be a Mullerian duct cyst. PMID- 2595879 TI - Continuous postoperative epidural analgesia in management of postoperative surgical pain. AB - In the last fifteen months we have used continuous postoperative epidural analgesia after open urologic surgery and herein report our experience with the first 64 patients. Incisional pain was completely eliminated in 96 percent of patients. Epidural analgesia diminished pain-related pulmonary complications without sedation. Complications were tolerable and manageable. Hypotension due to sympathetic blockade responds to intravenous fluid administration. Urinary retention is avoidable if the epidural infusion is discontinued prior to removing the urethral catheter. Itching is an undesirable consequence observed by 20 percent of patients when morphine is used. PMID- 2595880 TI - Long-term follow-up in patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) for transitional cell carcinoma of urinary bladder: cause for concern. AB - Twenty-one patients with high-stage transitional cell carcinoma (TCC) of the bladder were treated with a combination of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (M-VAC). There was a minimum follow-up of thirty-six months (range 36-45) in all patients. Patients were divided into three groups: 10 patients with recurrent TCC post radical cystectomy, 6 patients staged as T3/T4 or N1 treated in a neo-adjuvant setting, and 5 patients who received adjuvant M VAC four weeks post radical cystectomy. The overall initial response rate in patients with measurable disease was 68 percent (11 of 14), complete response rate 31 percent, and partial response rate 37 percent. There was no response in 31 percent. The durability of response in this series was very disappointing with all complete responders having recurrence of disease, with duration of responses ranging from eight to twenty-one months. Of the 5 patients who received M-VAC as adjunctive therapy, only 1 remains disease-free; the other 4 patients experienced disease progression four to seventeen months postoperative, and all have died. There was one drug-associated death due to nadir sepsis, and myelosuppression occurred in 12 patients. While M-VAC seems to be the best protocol currently available, the real durability of response is most disappointing. PMID- 2595881 TI - Histopathologic changes of transitional cell carcinoma of bladder after M-VAC chemotherapy. AB - Over the past several years, we have utilized methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) as definitive, neoadjuvant, and adjuvant therapy for various stages of transitional cell carcinoma with reduced toxicities. Currently, there is little information concerning the histopathologic changes after M-VAC therapy. We report on the histopathologic changes of bladder transitional cell carcinoma following M-VAC chemotherapy in our protocol for treatment of bladder cancer. The main histopathologic findings after M-VAC therapy are squamous metaplasia, necrosis, fibrosis, and persistent transitional cell carcinoma. In 2 cases, there were persistent adenocarcinoma and squamous cell carcinoma. The importance of these observations in terms of diagnostic and therapeutic implications is reviewed. PMID- 2595882 TI - Percutaneous nephrostomy tube with perirenal balloon fixation. AB - Despite a variety of available systems the fixation of nephrostomy catheters has not been solved satisfactorily so far. Secure and comfortable fixation of the presented nephrostomy tube is provided by its inflatable balloon which is placed in the perinephric space so that the abdominal wall will retain it. PMID- 2595883 TI - Effect of systemic glutathione depletion by buthionine sulfoximine on sensitivity of murine bladder cancer to cytotoxic agents. AB - The effect of systemic glutathione (GSH) depletion on sensitization of bladder cancer cells to various antineoplastic agents was investigated using murine model, MBT-2. Subcutaneous injection(s) of buthionine sulfoximine (BSO) significantly depleted the GSH content in the tumor and organs. BSO pretreatment produced significant enhancement in the antitumor effect of cyclophosphamide (CY), though it failed to sensitize the tumors to doxorubicin hydrochloride (Adriamycin), cisplatin, mitomycin C, JM-8, methotrexate, vinblastine, and tumor necrosis factor. Mice tolerated cytotoxic agents alone and in combination with BSO except for cisplatin in combination with BSO. A 29 percent (4/14) mortality rate was observed in mice treated with BSO and divided schedule of cisplatin. PMID- 2595884 TI - BCG in management of transitional cell carcinoma invasive to prostate. AB - Transitional cell carcinoma invading the prostate is a difficult problem to manage. Transurethral resection of the bladder neck followed by intravesical bacillus Calmette-Guerin (BCG) is one suggested option. PMID- 2595885 TI - Scrotal fistula from urethro-vasal reflux in paraplegia. AB - A case is presented of a paraplegic in whom urethro-vasal reflux and scrotal fistula developed. Urodynamics testing showed a hyperreflexic bladder with detrusor-external sphincter dyssynergia. PMID- 2595886 TI - Improved technique for implanting AMS 700CX inflatable penile prosthesis using transverse scrotal approach. PMID- 2595887 TI - Computerized tomography in evaluation of transitional cell carcinoma in bladder diverticula. AB - Between 1981 and 1985, 6 patients with transitional cell carcinoma in bladder diverticula had preoperative computerized tomography (CT). CT suggested no invasion through the wall of the diverticulum in all 5 patients who had pathologic confirmation. CT is a useful staging procedure and is helpful in determining the management of patients with transitional cell carcinoma. PMID- 2595888 TI - Urodynamic findings in interstitial cystitis. AB - The urodynamic findings in 41 women with proven interstitial cystitis were reviewed. All subjects had pain during bladder filling with sensory instability and limited functional capacity. Despite an average symptom duration of 5.7 years, all women had normal bladder wall compliance during cystometry. Fourteen of 41 women had additional significant urodynamic findings. PMID- 2595889 TI - [Anterior delimiting keratotomy in posttraumatic corneal cicatrices]. AB - Anterior dosed keratotomy has been tried for the correction of posttraumatic 'cicatricial' astigmatism. Virtually no data on the surgical treatment of 'cicatricial' astigmatism, particularly high, is available, whereas the presence of this condition is a contraindication to traditional keratotomy. The authors' data show good prospects of nontraditional keratotomy for the treatment of such conditions of the cornea. PMID- 2595890 TI - [A new method for restoring the patency of the lacrimal ducts in children]. AB - The advantages of the suggested technique are as follows: a ring-shape ligature of silicone capillary is a simple and effective method of treatment; fixation of the capillary terminals end-to-end at the site of exit from the lacrimal points permits an active life of the patient and is cosmetically quite satisfactory; the duration of the intubation may be under 1 year; the method is fairly simple, this helping to reduce the little patients' hospital stay and permitting outpatient treatment for older children. PMID- 2595891 TI - [Ocular prosthesis following plastic surgery]. AB - The shape of the eye prostheses depends on the plastic surgery type. Standard prostheses with thin but not sharp edges are used to recreate the conjunctival cavity, prostheses with a deep retraction or flat ones are employed for a delayed introduction into the stump, prostheses with a 'swelling' at the upper edge are of use in surgery to correct the upper eyelid falling in, prostheses with a flattened lower edge and a 'shelf' at the upper edge are used to fortify the lower eyelid. Individual prostheses are recommended after plastic surgery. The prostheses should not prevent free closing and blinking of the eyelids, retaining the identical opening of the eyes. An inadequately chosen prosthesis brings to nothing the tremendous work made by the surgeon. Ocular prosthetics may be regarded as the final stage stabilizing the results of plastic surgery. PMID- 2595892 TI - [Orbital ectoprosthesis as a method for rehabilitating anophthalmic patients]. AB - Orbital ectoprosthesis is a method for rehabilitation of anophthalmia patients with severe extensive injuries in the orbital area. Analysis of 1230 case histories has helped define the indications and contraindications to this type of care. Good cosmetic results have been achieved in all the patients. PMID- 2595893 TI - [The possibilities for predicting and preventing postoperative inflammatory complications in intraocular correction]. AB - Measurements of unsaturated fatty acid diene conjugates in the anterior chamber humor are recommended to predict postoperative inflammatory complications. If their levels are increased, antioxidants should be included in the therapeutic scheme along with antibiotics and corticosteroids. PMID- 2595894 TI - [The status of the iridocorneal angle after the implantation of anterior chamber intraocular lenses with flexible supporting elements]. AB - The study was undertaken to examine the status of the iridocorneal angle (ICA) 1 to 4 years after implantation of anterior chamber intraocular lens with flexible supporting devices designed by M. L. Dvali. Correct implantation and gonioscopic monitoring wherein were found to provide reliable lens fixation, as a rule, in the area of the scleral spur and, occasionally, to the anterior part of the ciliary body, if the latter was broad. Additional fixation of the supporting devices was attained by delicate commissures at their small extent at the sites of iris contact, which were detected in the majority of cases. Strangulation of the iris or fixation in its periapical part occurred in small cases and were observed in the upper portion of ICA. Corneal epithelial contact with the supporting devices was revealed in 5.4% of cases, as well as in the upper part of ICA. Only in 1 out of 37 cases, the changes in the drainage area such as iris strangulation at a great extent were sufficient to impair its function and required additional surgical correction. The remaining eyes showed no abnormal intraocular fluid circulation. The visual acuity in 35 eyes was as great as 0.5 or more. PMID- 2595895 TI - [The first results of the contact lens correction of aphakia in young infants]. AB - Soft contact lenses (SCL) were used for the correction of aphakia in young children. Eleven surgeries were carried out in 7 children with congenital cataracts (aspiration in 2 cases and transciliary lensectomy in the rest). SCLs were made individually of gel with 70% water content by mechanical treatment, their parameters differing from the commercial 'aphakic' lenses. These SCL parameters were chosen with consideration for the data of measurements of the corneal curvature and diameter, carried out during surgery and then specified by trials. To determine the optic force of SCL, a special formula and skiascopy were used. Only in one case the parents refused from SCL application, being satisfied with the cosmetic effect of surgery; in the rest cases SCLs were tolerated satisfactorily as evidenced by a follow-up of 3 to 8 months. SCL wearing improved the visual function, that manifested in a more stable fixation, reduction and stabilization of strabismus angle, development of an ability to recognise closely situated small articles. These results are in fact tentative; further studies will be aimed at a more accurate assessment of the visual function and of the corneal status (including the status of the endothelium). PMID- 2595896 TI - [The role of early contact lens correction in the rehabilitation of nursing infants with aphakia]. AB - The authors analyze the results of early (on days 5-8 postoperation) contact correction with soft contact lenses (SCL), carried out in 126 infants (206 eyes), operated on for congenital cataract extraction at the age of 2-12 mos. Soviet IOZM, Czechoslovak Spofa-lens, and American Bausch and Lomb lenses have been applied for 18-14 hrs daily, in parallel with the treatment for amblyopia (direct occlusion, a total exposure of the retina), carried out at home. A thorough adaptation, observance of the hygiene and schedule of the lens use have been a guarantee of the absence of ocular complications. SCLs considerably improve the vision acuity and are recommended for early correction of aphakia after congenital cataract extraction, carried out during the first months of infant life. PMID- 2595897 TI - [The design characteristics of bifocal contact lenses]. AB - Problems associated with the correction of presbyopia with bifocal contact lenses are discussed. The designs of bifocal contact lenses manufactured by the major foreign firms are analyzed. PMID- 2595899 TI - [The retinal pigment epithelium in patients with sclerotic macular dystrophy before and after transection of the superficial temporal artery]. AB - The authors have examined the effect of crossing the superficial temporal artery on the retinal pigmented epithelium in patients with sclerotic macular dystrophy. Three groups of patients with different initial values of electrooculogram Arden's coefficient were examined. Circulation in the vascular membrane of the eye has improved in 76% of patients after surgery. This lead to the normalization of Arden's coefficient in cases with the initially abnormal parameters, which fact evidences the improvement of the retinal pigmented epithelium function after the operation. PMID- 2595898 TI - [The clinical picture and diagnosis of optic nerve gliomas in adults]. AB - Gliomas of the optic nerve are more often in childhood and adolescence. The present paper analyzes the clinical features and diagnosis of optic nerve gliomas in 41 adult patients aged 15 to 56. Comparative analysis of the clinical picture and diagnostic specificities in optic nerve gliomas in adults and children has revealed a longer duration of the disease, less manifest exophthalmos and dilatation of the optic canal on the side of the tumor in adults. Analysis of computerized tomography data has prompted singling out 2 types of optic nerve glioma images: (1) spindle-shaped dilatation of the optic nerve in the orbit and (2) even thickening of the optic nerve along its whole length in the orbit. Each of these glioma tomographic images is associated with specific clinical features. Differential diagnosis between optic nerve gliomas and meningiomas in adults in described. PMID- 2595900 TI - [Symptomatic treatment of terminal painful glaucoma by the retrobulbar administration of aminazine]. AB - Retrobulbar injection of 1.0-2.5% aminazin solution in terminal painful glaucoma helps avoid enucleation in 83.8% of cases. The analgesic effect of retrobulbar aminazin does not always accurately correlate with its hypotensive action on the intraocular pressure. The mechanism of the drug action is explained by a local (on the ciliary node) manifestation of aminazin neurotropism depressing the eye sensitivity to pain. PMID- 2595901 TI - [The effect of the method for forming the conjunctival flap in glaucoma fistulizing operations on the development of a stable acquired ptosis of the upper eyelid]. AB - The relationship between the incidence rate and severity of acquired ptosis and the technique of the conjunctival flap formation in trabeculectomy were under study. A total of 117 patients were followed up. In 70 the flap was formed by the traditional method, with the foot to the limbus, and in 47 by the nontraditional technique, with the foot to the vault and radially. Stubborn (a follow-up of more than 6 mos postoperation) acquired ptosis of the upper eyelid was observed in 38.5% of patients; it was more often after the traditional technique of the conjunctival flap formation (48.6%) and rare and approximately to the same extent when nontraditional methods were used (23.4%). The incidence rate and severity of ptosis increase as the height of the incision on the conjunctiva (from the limbus), made by the traditional technique of the flap formation, grows. A more frequent development of ptosis after traditional formation of the conjunctival flap vs. the nontraditional techniques may be explained by injuries to the individual branches of the oculomotor nerve, participating in the innervation of the posterior peduncle of the levator muscle of the upper eyelid. PMID- 2595902 TI - [The results of research on the antioxidant emoksipin in clinical eye diseases]. AB - Emoxipin, a new lipid peroxidation inhibitor, has been used in the treatment of various ophthalmic diseases. The drug is characterized by a retinal-protective and an additional fibrinolytic effects; it has been effectively used to preserve the visual function in glaucoma, to treat intraocular hemorrhages and retinal injuries with physical, chemical, or bacterial factors. A manifest effect has been observed in 87% of 106 patients (118 eyes) with various ocular abnormalities. Emoxipin is recommended for the treatment of a variety of ocular diseases. PMID- 2595904 TI - [Dynamic functional and electrophysiological indices in patients with complicated high myopia after revascularizing operations]. AB - Vision acuity and differential photosensitivity were examined, and electroretinography and electrooculography data analyzed in patients with high myopia after crossing the superficial temporal artery. A tendency to normalization of these parameters has been observed after surgery, due to improvement of the circulation in the orbital artery basin, as evidenced by ultrasonic dopplerography. The method of automated statistical perimetry was found valuable for predicting the functional results of surgery and for objective assessment of visual functions postoperation. PMID- 2595903 TI - [The experimental action of continuous YAG-laser radiation on the structures of the posterior eye segment]. AB - The effects of fiber optics YAG laser continuous irradiation on the structures of the posterior segment of the eye in endovitreal exposure were under study. The values of the 1.06 microns wavelength radiation absorption by the membranes of the posterior segment of the eye were defined. On the basis of mathematical computations a relationship was revealed between standard temperature and the length of exposure in various diameters of the focussed spot and radiation power of 1 W, confirmed by animal experiments. PMID- 2595905 TI - [Hemorrhages in myopia (based on clinical and fluorescence angiographic data)]. AB - The authors analyze the results of examinations of 50 patients (70 eyes) with complicated high myopia, corrected by contact lenses. The mean visual acuity of patients in spectacles has been 0.21, in contact lenses 0.45. Hemorrhages in the fundus oculi have been detected in all the patients, these hemorrhages being a complication of myopia. Basing on the clinical and fluorescent angiography data, the authors have distinguished 2 types of myopic hemorrhages, differing in the origin, course, and outcome. Recommendations on the treatment, strategy and optic correction for patients with high myopia complicated with hemorrhages in the fundus oculi are given. PMID- 2595906 TI - [Infectious inflammatory diseases of the external portion of the eye (the results of a discussion)]. PMID- 2595907 TI - [Heterotopic formation of bone tissue in the eye]. PMID- 2595908 TI - [Sebaceous gland adenoma of the eyelid]. PMID- 2595909 TI - [Decompression operations on the optic nerve in glaucoma]. AB - The authors give theoretical grounds and experimental validation for surgery on the optic nerve to eliminate its atrophic changes in glaucoma. They suggest a technique of the direct intervention at the site of the optic disk, approaching it from the side of the eye cavity. A method for the optic nerve decompression at the site of its stem portion via an extraocular approach is suggested. Experimental studies have demonstrated the possibility of enlarging the volume of the optic nerve scleral canal by discission of its narrowest section, the scleral ring; this operation essentially decreases twisting and deformation of the nerve fibers and main vessels of the retina. Clinical results of decompression surgery in 32 patients with far-progressed glaucoma are analyzed. Improvement of the visual function and stabilization of the glaucomatous process were observed in all the patients both in the immediate and late postoperative periods. The retinal and optic nerve blood microcirculation were found to improve after the suggested decompression surgery. PMID- 2595911 TI - [Principles of active surgical treatment of anaerobic non-clostridial infection of soft tissues]. PMID- 2595910 TI - [Prevention and treatment of thromboembolic complications in patients with facial furunculosis and carbuncles]. PMID- 2595912 TI - [Surgical tactics in reducible hernias]. PMID- 2595913 TI - [Late results of endoscopic papillosphincterotomy in patients with non-neoplastic diseases of the common bile duct]. AB - An investigation of long-term results of treatment of 226 patients has shown that endoscopic papillosphincterotomy is a highly effective method of treatment of patients with cholelithiasis and stenosis of the major duodenal papilla. The complex use of the surgical and endoscopic methods of treatment gave most favorable results. PMID- 2595914 TI - [Various aspects of the organization of medical services for patients with ischemic heart disease in the USSR]. PMID- 2595916 TI - [An attachment for the operating table to facilitate trans- osseous osteosynthesis of the upper extremity]. PMID- 2595915 TI - [A method of correction of posterior dislocation of the fingers in post-burn deformity of the hand]. PMID- 2595917 TI - [Therapeutic tactics in inflammatory diseases of the gallbladder in patients with bronchial asthma]. AB - The authors describe curative methods of treatment of inflammatory diseases of the gallbladder in 12 patients with bronchial asthma. Sanitation of the surgical infection focus (cholecystectomy) improves the clinical course of bronchial asthma, positively influences the immune status of the patients. PMID- 2595919 TI - [Characteristics of the clinical course of gunshot peritonitis]. AB - The article gives characteristics of specific features of the clinical course of gunshot peritonitis due to specificity of the mechanism of the formation of gunshot wounds. Characteristic features of the clinical course of gunshot peritonitis are: high rate of the development of pathomorphological alterations in the abdominal cavity and severity of clinical manifestations. The multiple organ insufficiency in gunshot peritonitis at first is of primary character followed by the development of secondary organic insufficiency due to the progressing infectious process in the abdominal cavity. PMID- 2595918 TI - [Temporary clamping of the lobar portal tracts during surgical operations on the liver]. PMID- 2595920 TI - [A method of extracorporeal perfusion of the sections of xenogeneic spleen]. AB - A method of extracorporeal perfusion of sections of the swine spleen developed by the authors is described. Perfusion of the swine spleen sections was performed in the small volume perfusion chamber (100 cm3) with a 80-100 ml/min rate for 30-60 min with the help of a roller pump. The extracorporeal contour was connected with the major veins of the patient. An experience with the treatment of 23 patients with pyo-septic diseases with the use of extracorporeal perfusion of the swine spleen sections shows the efficiency, simplicity and safety of the proposed method. PMID- 2595922 TI - [Non-surgical sanitation in patients with obstetrical and gynecological infections]. AB - The intra-aortic++ introduction of a complex of drugs was performed to 34 patients with sepsis of obstetric-gynecological etiology. The disease appeared in 23 patients after extrahospital abortions, in 7 patients after delivery, in 4 patients after operation of cesarean section. Septic pneumonia took place in 23 patients. Antiseptic treatment was also used in all the patients. Recovery was noted in 32 of 34 patients, 23 of them were discharged from the hospital without removal of the uterus. Conclusion may be made that the intra-aortic++ administration of drugs is a highly effective method of treatment of obstetric gynecological sepsis. PMID- 2595921 TI - [Effect of transfusion of UV-irradiated blood on the changes in serum cholinesterase activity in patients with peritonitis]. AB - The article presents an analysis of dynamics of changes of serum cholinesterase activity in patients with peritonitis resulting from the effect of UVI blood. It was established that it resulted in more rapid recovery of the functional activity of hepatocytes. A serial investigation of fluctuations of the serum cholinesterase activity may serve a criterion for the assessment of prognosis of the disease. PMID- 2595923 TI - [Pathogenesis of jaundice in acute cholecystitis]. AB - An investigation of specific course of the disease in 911 patients operated upon for acute cholecystitis with bilirubinemia has shown that mechanical jaundice resulting from choledocholithiasis takes place in a third of the patients. Obstruction of the bile duct was confirmed in 27.1% of the patients during cholangiography. Prevalence of a number of factors was noted indicating of a toxic lesion of the liver (destructive forms of acute cholecystitis in 81.0% of the patients, higher level of bilirubinemia in long terms of the disease, the presence of coexistent pancreatitis in 30.5%, cholangitis--in 39.3%). An investigation of 207 bioptates of the liver in acute cholecystitis has revealed fatty degeneration of hepatocytes in 56.5%, pericholangitis--in 43.0%, cholestasis--in 21.3% of the cases. The cause of jaundice in acute cholecystitis mainly is an alteration of the hepatic cells due to pyo-resorptive intoxication manifested as cholestasis and hepatitis. PMID- 2595924 TI - [Use of helium-neon lasers in the treatment of peptic ulcer]. AB - An analysis of treatment of ulcer disease of the stomach and duodenum with the help of helium-neon lasers has been made. The pathological focus (ulcer) was influenced in two ways: through the endoscope and by means of biologically active points. Positive effects were obtained in 96.9% of the patients. Operations were performed on 3.1% of the patients where laser therapy failed to give good effects. Contraindications to laser therapy were considered to be bleeding, callous and malignant ulcers. PMID- 2595925 TI - [Intestinal obstruction in extensive postoperative ventral hernia]. AB - The work is based on an experience with surgical treatment of 1017 patients. Intermittent intestinal obstruction was observed in more than 40% of them and was not always dependent on the character of commissural processes. The most frequent cause of its appearance is a combination of commissures with a considerable ptosis and formation of flexions, angular deformities and incomplete torsion of intestinal loops. Supermedial and subcostal hernias with most pronounced commissural processes are comparatively rarely followed by intestinal obstructions (12.5%). It was more often observed in middle- and inferior-medial (56.1%) and iliac (33.3%) hernias with less spreaded commissures. PMID- 2595926 TI - [Preventive use of immunostimulants in patients with infectious endocarditis]. AB - Leakadine++, levamisole++, proper-myl were used in the postoperative period in 36 patients operated upon for infectious endocarditis with regard for the character of the immunopathology found. The directed immunostimulation results in resolution of immunodeficiency and normalization of the immune status of the patients. PMID- 2595927 TI - [Laser sanitation of pleural empyema in patients with cancer of the lungs]. AB - The work shows a possibility to use copper steam laser irradiation for treatment of postoperative pleura empyema in patients with lung cancer. Good effects of sanitation were obtained in 27 of 28 patients: 12 patients were cured, the rest of the patients had 6-8 months long remission. PMID- 2595928 TI - [Hemodynamic aspects of the treatment of patients with "critical ischemia" of the lower extremities]. AB - A complex examination of 60 patients with different stages of disturbances of blood circulation (by the Fontain classification) with chronic arterial insufficiency was performed. Specific features of regional hemodynamics were revealed in patient with "critical ischemia" (3rd and 4th stages of the disease). Threshold values of the "critical ischemia" were determined, most informative of them being the malleolus index and oxygen pressure on the foot. An analysis of results of the investigation in the dynamics of the treatment performed has shown possible effectiveness of restorative operations in treatment of patients with severe stages of chronic arterial insufficiency. PMID- 2595929 TI - [Hemodynamic changes in patients with arteriosclerosis obliterans of the lower extremities after restoration of the circulation]. AB - It was established that reconstructive operations allow to adequately reestablish regional hemodynamics, the linear and capacitance velocity of the blood flow along the explant in the group of prosthesis being close to the values of patients in the group of shunting. The data obtained allow to make a conclusion on high efficiency of shunting by the method of transprosthesis aortotomy in patients with obliterating arteriosclerosis of lower extremities. PMID- 2595930 TI - [Regional blood flow velocity as a prognostic factor in the treatment of suppurative and necrotic lesions of the foot in diabetes mellitus]. PMID- 2595931 TI - [Surgical tactics in acute thrombophlebitis of the superficial veins of the lower extremities]. AB - A 20-years experience of the clinic with substantiation of the surgeon's tactics for acute thrombophlebitis of superficial veins of lower extremities is presented. A conclusion is made that radical operations for acute thrombophlebitis of superficial veins of lower extremities without special preoperative preparation prevent further spread of the thrombotic process, development of thromboembolism of the pulmonary artery, make the duration of treatment at the hospital 2 times shorter and contributes to quicker recovery of working ability. PMID- 2595932 TI - [Surgical treatment of herniation of lumbar intervertebral disks]. AB - An analysis of outcomes of treatment of 288 patients has shown that using the microsurgical technique when removing hernias of lumbar disks allows to perform more sharing manipulations with the roots, vessels and disk, gives favorable results of treatment. Good outcomes were obtained in 68 patients, satisfactory- in 12 patients, bad--in 2 patients. The period of the intrahospital treatment became shorter. PMID- 2595933 TI - [Serous cyst of the round ligament of the liver]. PMID- 2595934 TI - [Rare variant of the structure of extrahepatic bile ducts]. PMID- 2595935 TI - [Conservative treatment of Bouveret's syndrome]. PMID- 2595936 TI - [Cancer of the ureter complicated by pyelonephritis in a patient with acute myocardial infarction]. PMID- 2595937 TI - [Suppurative abscess in the right half of the scrotum as a complication of acute appendicitis]. PMID- 2595939 TI - [Malignant hemangiopericytoma of the greater omentum]. PMID- 2595938 TI - [Severe intra-abdominal trauma in criminal abortion]. PMID- 2595940 TI - [Scintigraphy of the liver and biliary tract in the diagnosis of diseases associated with mechanical jaundice]. PMID- 2595941 TI - [The piriform muscle syndrome]. PMID- 2595942 TI - [Various characteristics of the clinical course of sarcoma of the prostate]. PMID- 2595943 TI - [Immunologic reactivity of young children with severe forms of suppurative diseases of the lungs and pleura and the methods of its correction]. PMID- 2595944 TI - [Surgical tactics in spontaneous external intestinal fistulas in children]. PMID- 2595945 TI - ["Accessory liver" as a cause of extrahepatic form of portal hypertension in children]. PMID- 2595946 TI - [Hemorrhage from polyp of the gallbladder in a child]. PMID- 2595947 TI - [Surgical treatment of hydronephrosis of conjoined kidneys in children]. PMID- 2595948 TI - [Total rupture of the diaphragm with displacement of the liver into the thoracic cavity in a child]. PMID- 2595949 TI - [Skeletal traction as the stage in surgical correction of severe spinal deformities in children]. PMID- 2595950 TI - [Posterior-external dislocation of both forearm bones with fracture of the internal epicondyle in children]. PMID- 2595951 TI - [Expediency of administration of fluorocarbon emulsion into the body of a cadaveric donor before taking the kidneys for transplantation]. PMID- 2595952 TI - [Planned surgery of "retrobulbar" duodenal ulcers]. PMID- 2595953 TI - [Morphogenetic basis of complications of resection of the intestines and their prevention]. PMID- 2595954 TI - Critical care. PMID- 2595955 TI - Abnormal bleeding. AB - Animals with disorders of hemostasis are often presented as emergency patients and, as such, offer a challenge to the attending clinician. This article reviews the basic physiology of hemostasis and laboratory tests used for diagnosis. Guidelines for the evaluation and treatment of patients with bleeding disorders are provided. PMID- 2595956 TI - Effects of general anaesthesia on static respiratory compliance in dogs. AB - The effect of anaesthesia on total, pulmonary and chest wall static respiratory compliance was investigated in healthy spontaneously breathing dogs undergoing orthopaedic surgery. Total compliance fell by 26 per cent from the baseline measurement within 25 minutes of the first measurement (P less than 0.01), while pulmonary and chest wall compliances fell by 34 per cent and 40 per cent, respectively (P less than 0.01). Pulmonary compliance ceased to fall after 50 minutes, but chest wall compliance was still declining after 70 minutes. The decline in compliance could be prevented by periodic full lung inflation, with a significant difference being found between inflated and uninflated dogs (P less than 0.01). The reduction in compliance during anaesthesia is believed to be a consequence of reduced functional residual capacity and the development of lung tissue atelectasis. PMID- 2595957 TI - Water deprivation in weaned pigs. PMID- 2595958 TI - Drugs for pigeons. PMID- 2595959 TI - Morbillivirus infections in seals. PMID- 2595960 TI - Infrared thermography for detecting sweet itch. PMID- 2595961 TI - Medicines--advice on their use in animals. PMID- 2595962 TI - MAFF Salmonella policy attacked. PMID- 2595963 TI - Movement of veterinarians in the EC. PMID- 2595964 TI - Collecting those debts. PMID- 2595965 TI - Employment survey: 1978 graduates. PMID- 2595966 TI - Phenylpropanolamine: an alpha-adrenergic agent for the management of urinary incontinence in the bitch associated with urethral sphincter mechanism incompetence. AB - Ten bitches with urinary incontinence due to incompetence of the urethral sphincter mechanism were treated with phenylpropanolamine hydrochloride at a dose of either 1 mg/kg orally three times daily or 2 mg/kg orally once daily in a prolonged release formulation. The signs of incontinence resolved in all the bitches, and improvements were maintained over periods ranging from one to more than two years, except in one bitch which became refractory to treatment after three months. One bitch which was inadvertently treated at a dose rate of 2.5 mg/kg showed signs of lethargy and inappetence but returned to normal when the dose rate was reduced. PMID- 2595967 TI - Observations on Cysticercus bovis in slaughter cattle in the Matabeleland province of Zimbabwe. AB - Cysticercus bovis was detected at meat inspection in 2.16 per cent of 102,087 carcases of cattle from Matabeleland Province, slaughtered in Bulawayo during a period of 11 months. Lightly infested (detained) carcases accounted for 95 per cent of those with cysticercosis. The head was the only site affected in 58.4 per cent of the detained carcases, the shoulder in 20.1 per cent and the heart in 7.9 per cent. In more heavily infested (condemned) carcases 81.1 per cent had at least three sites affected. The incidence of cysts was highest in older male animals but in younger animals it was highest in cows. In the detained carcases an average of 1.5 cysts were found, of which 76 per cent were live and 24 per cent dead. Condemned carcases had more than 58 cysts on average, of which 98 per cent were live and 2 per cent dead. Live cysts were more common in older cattle and dead cysts were more common in younger animals. The incidence of C bovis in carcases of cattle originating from communal areas was 3.2 per cent compared with 1.6 per cent in those originating from commercial farms. PMID- 2595968 TI - Taylorella equigenitalis isolated from an aborted foal. PMID- 2595969 TI - Congenital neosporosis in a calf. PMID- 2595970 TI - Acute necrotising hepatitis in Danish farmed hares. PMID- 2595971 TI - 'Veterinary relief service'. PMID- 2595972 TI - African horse sickness in Saudi Arabia. PMID- 2595973 TI - Prescription of POMs. PMID- 2595974 TI - Alternative medicine. PMID- 2595975 TI - Caecal dilatation. PMID- 2595976 TI - Isolation of Pasteurella haemolytica from teat lesions in ewes. PMID- 2595977 TI - Retirement. AB - Retirement should be carefully thought through and sensible plans made for the future. It is a time of challenge for what lies ahead not disappointment at what has been. As you shut one door another will open and it is up to each individual to ensure that this will lead to a productive, satisfying and enjoyable way of life. PMID- 2595978 TI - Field efficacy of ivermectin, fenbendazole and pyrantel embonate paste anthelmintics in horses. AB - Three anthelmintic pastes were compared in terms of their ability to suppress the output of parasite eggs in the faeces of 108 grazing horses at four sites in Britain; the horses were treated once with either ivermectin, fenbendazole or pyrantel. At each site, the horses grazed together throughout the trials which took place during the summers of 1985 and 1986. The median periods before parasite eggs reappeared in faeces were 70 days for ivermectin, 14 days for fenbendazole and 39 days for pyrantel embonate. Geometric mean faecal egg counts in the groups treated with ivermectin and pyrantel were significantly less (P less than 0.05) than in the fenbendazole group on days 21, 28, 35 and 42 after treatment. On days 49, 56, 63 and 70 the mean egg counts in the ivermectin group were significantly lower (P less than 0.05) than those in either of the other groups. The results indicated that in order to ensure minimal contamination of pastures, grazing horses treated with ivermectin paste would have required a second treatment approximately 10 weeks after the first, and to achieve similar control with fenbendazole or pyrantel embonate, a second treatment would have been required after approximately two weeks and six weeks, respectively. PMID- 2595979 TI - Natural causes of death in non-suckling grey seals (Halichoerus grypus). AB - Thirty-four grey seals which died of natural causes were examined. They ranged in age from aborted fetuses to adults, but suckling pups were excluded from the study. The commonest primary cause of death was pneumonia and a variety of parasitoses occurred as secondary lesions. PMID- 2595980 TI - Stretching movements in fetal lambs in late gestation. PMID- 2595981 TI - Clofazimine for the treatment of fistulous withers in three horses. PMID- 2595982 TI - Competitive exclusion--Salmonella in poultry. PMID- 2595983 TI - Ibuprofen poisoning in dogs. PMID- 2595984 TI - Problems over litigation. PMID- 2595985 TI - Meat inspection. PMID- 2595986 TI - Encouraging trend in incidence of human salmonellosis. PMID- 2595987 TI - MAFF investigates scale of lead poisoning. PMID- 2595988 TI - Paper avalanche causes FVE problems. PMID- 2595989 TI - Timing the mating of dogs on the basis of blood progesterone concentration. AB - The optimal time for mating bitches was determined by measuring the progesterone concentration in peripheral blood three times a week after the start of vulval bleeding. Of 104 bitches with reduced fertility 81 (78 per cent) became pregnant and of 112 bitches with normal fertility 105 (94 per cent) became pregnant. Of 121 bitches mated once, 102 (84 per cent) became pregnant, and of 95 bitches mated more than once, 84 (88 per cent) became pregnant. The mean (+/- sd) interval between the start of vulval bleeding and the optimal time for mating in 88 bitches was 11.8 +/- 3.1 days. The blood progesterone concentration appears to be an excellent indicator of the best time for mating, particularly in bitches with reduced fertility. PMID- 2595990 TI - Influence of clenbuterol on mucociliary transport in healthy horses and horses with chronic obstructive pulmonary disease. AB - The mucociliary tracheal transport rate and clearance index were measured in 16 healthy horses and 16 horses suffering from chronic obstructive pulmonary disease. A marker, Indian ink in syrup, was placed in the mucus layer of the interior wall of the trachea, just in front of the carina, and its displacement was measured after 30 and 60 minutes. The same procedure was repeated 30 minutes after the intravenous administration of 0.8 microgram clenbuterol/kg bodyweight. In the diseased horses the mucociliary transport rate was significantly lower than in the healthy horses. After clenbuterol administration there was a significant increase in the transport rate and a similar increase in the clearance index. Sixty and 90 minutes after clenbuterol there was a significant increase of mucus secretion in both the healthy and diseased horses. Measurements in five healthy horses and five diseased horses on two different days gave similar results, showing that the technique provided reproducible data. PMID- 2595991 TI - Mucosal disease in a cow and her suckled calf. PMID- 2595992 TI - Spread of heartwater along trek routes in Shaba (south east Zaire). PMID- 2595993 TI - Lead poisoning from contaminated feed. PMID- 2595994 TI - Survey of practice fee structure. PMID- 2595995 TI - Chlamydia psittaci infection in robins. PMID- 2595996 TI - POM advertising. PMID- 2595997 TI - Oversized bovine fetuses. PMID- 2595998 TI - [Roentgeno-functional studies in ectopia of the anal canal in children]. AB - Analysis of x-ray data on 70 pediatric patients aged one day-15 yrs, was performed. In 55 cases the investigation was conducted before the correction of ectopia of the anal canal, in 11 cases after the previously described operation for forming the anal orifice (FAO), in 4 cases there was stenosis of the anal orifice without ectopia. Radiograms performed during irrigoscopy and (or) with a Foley catheter were assessed. Weakening and then complete incompetence of the puborectal muscle, determining incontinence of feces, were shown to be proportional to age and a degree of stenosis of the colon orifice. A necessity of radical operation in the second half-year of the life or measures to ensure adequate bowel evacuation were shown. PMID- 2595999 TI - [Clinico-roentgenologic signs of osteo- and arthropathy in children with syringomyelia]. AB - Syringomyelia is a severe dysontogenetic lesion of the nervous system with polymorphous clinical and x-ray manifestations. The authors followed up 10 children aged 4-12 with osteo- and arthropathies, and presented a clinical and x ray picture characterizing this process. They described in detail x-ray signs of this lesion over time and the formation of neoarthroses in the fracture areas, changes in zones of preliminary calcification and epiphyseal cartilage as well as in flat pelvic bones. PMID- 2596001 TI - [Wide-screen fluorography in the diagnosis of ischemic heart disease and arterial hypertension]. AB - A study was made of the results of 2-projectional fluorography of the chest in 1290 men aged 40 to 60 (890 outpatients taking prophylactic cardiological check up and 400 inpatients with CHD or essential hypertension). The detectability of cardiac and aortic pathology by prophylactic fluorography was 5-fold higher than pulmonary pathology. Changes of the heart, aorta and pulmonary hemodynamics in CHD and arterial hypertension were characterized. The results of fluorocardiometry in the groups of examinees with various CHD risk factors were presented. PMID- 2596000 TI - [Efficacy of the methods of radiation protection in childhood radiography]. PMID- 2596002 TI - [The x-ray diagnosis of exudative pericarditis]. AB - Venous hypertension of lesser circulation was used as a criterion for differential diagnosis of diffuse lesion of the myocardium and exudative pericarditis. In 57 patients (31 with diffuse myocardial lesion and 26 with exudative pericarditis) the results of assessment of common x-ray symptoms were compared with signs of venous hypertension in this disease. The presence or absence of venous hypertension in the recognition of exudate into the pericardial cavity was emphasized. PMID- 2596003 TI - [Radiodiagnosis of diseases of the genital system in girls]. AB - Based on a study of an x-ray picture of the small pelvis, cranium and bone system in 400 girls aged 10-18, the results of the use of various roentgeno-radiological methods were analyzed, their diagnostic value was shown, and the data were compared with those of ultrasound investigation. PMID- 2596004 TI - [Cineangiographic diagnosis of an aneurysm of the membranous part of the heart septum]. AB - Altogether 20 patients with aneurysm of the cardiac membranous septum (AMS) were examined. Biplane cineangiocardiography (CACG) of the left ventricle was performed in the left oblique position permitting the detection of AMS in 17.8% of the patients with the suspected interventricular septal defect (IVSD). Heart diseases were observed in all the patients, in 90% they were accompanied by IVSD in the cardiac wall. AMS regular contours and a wide base were signs of true AMS. A narrow base and irregular shape were indicative of false AMS. Slight aortic transposition was noted in 1/4 of the patients with AMS. PMID- 2596005 TI - [A comparative evaluation of cinecoronarography and digital subtraction coronarography]. AB - The results of cinecoronarography (cine-CG) and computerized subtraction angiography (CSA) in 60 CHD patients were analyzed. The percentage of narrowing of the coronary arterial diameter, the percentage of a stenosed area, the minimum diameter of a stenosed part and the extent of lesion were determined. Insignificant correlation was noted in important categories of lesions of medium extent and expression resulting from lesser spatial resolution of CSA. PMID- 2596006 TI - [Anatomically corrected transposition of the great vessels]. AB - The paper is concerned with the description of a rare congenital heart disease: anatomically corrected malposition of major vessels in a 9-mos 24 day old girl. The diagnosis of this disease was shown on the results of angiocardiography, concomitant congenital heart diseases were described. This abnormality is characterized by common atrioventricular and ventriculovascular joints and inversion position of the major vessels, it is always attended by congenital heart diseases, such as an interventricular septal defect combined with pulmonary stenosis. Surgical intervention is aimed at the elimination of concomitant heart diseases. PMID- 2596007 TI - [Experimental and clinical rationale for the choice of optimal methods of x-ray diagnosis of kidney diseases]. AB - Limits of potentialities of methods of radiodiagnosis of renal diseases were studied by way of experimental simulation of organs with various pathomorphological changes (urolithiasis, kidney tumors and tuberculosis). Special attention was paid to the detection of pathomorphological elements which were characteristic for the initial forms of disease. Photofilm and thermoluminescent dosimetry were used to study radiation-hygienic characteristics of radiation methods of kidney investigation. Recommendations for establishing diagnosis were worked out in suspected urolithiasis, kidney tumors and tuberculosis. The thickness of a studied object played an important role in the detectability of minor and low contrast details. An objective method of the control over the quality of roentgenocontrast images was proposed. PMID- 2596008 TI - [The use of programmable microcalculators in x-ray diagnosis]. PMID- 2596009 TI - [X-ray diagnosis of changes in the bones in congenital syphilis]. PMID- 2596010 TI - [The effect of embolization of an aneurysmal splenic artery]. PMID- 2596011 TI - [A primary sarcoma of the heart]. PMID- 2596012 TI - [A method of marking fluorograms]. PMID- 2596013 TI - [The role of the fluorographic diagnostic room in a multiprofile municipal clinical hospital]. PMID- 2596015 TI - [Initial experience with the use of a mobile version of the computed tomograph in the USSR]. PMID- 2596014 TI - [Experience in the organization of the work of the Section of Pediatric Roentgenologists of the Zaporozhye Oblast Scientific Society of Roentgenologists and Radiologists]. PMID- 2596016 TI - [The use of a mobile computed tomograph]. PMID- 2596017 TI - [The role of grandparents in the development of good habits in grandchildren]. PMID- 2596018 TI - Epidemiological aspects of the evolution of influenza infections in a large urban centre (B.) in Romania in 1988. AB - The study describes the peculiarities of the influenza infection evolution, in 1988, in a large urban centre, B., in Romania, as they result from the active surveillance of the epidemiological process of influenza and other viral respiratory tract infections, by means of a complex methodology based on clinical epidemiological and laboratory techniques. The low endemic morbidity, the evolution of these seasonally ascendant specific incidence, the endemic aspect of influenza infection being maintained as a consequence of its predominance in infants and children, the clinically mild form of the outbreaks, all these are specific elements of the epidemiologic impact in the surveyed territory. They are discussed in accordance with the results of laboratory tests (seroepidemiologic and diagnostic) that confirmed the permanent circulation of influenza virus types A(H1N1), A(H3N2) and B in all age groups. PMID- 2596019 TI - Nucleotide sequence analysis of the capsid genes and the right-hand terminal palindrome of porcine parvovirus, strain NADL-2. AB - The genome of the porcine parvovirus, strain NADL-2, has been cloned and the sequence of map units 28 to 100, which is 3670 bp in length and contains the capsid coding regions and the right-hand terminal palindrome, has been determined. The sequence shows extensive homology with other parvoviruses such as MVM, H-1, CPV, and FPV in the capsid coding region. Given the information available from these sequences, the regulatory and capsid coding regions for PPV have been proposed and the amino acid sequences of capsid proteins compared. The right end, which has a 188-nucleotide-long imperfect palindromic sequence, has an organization similar to that of other parvoviruses and the homologies in this region with other parvoviruses correspond to the homologies observed in the rest of the respective genomes. PMID- 2596020 TI - Identification and subcellular localization of a putative cell-to-cell transport protein from red clover mottle virus. AB - To investigate the mode of gene expression of red clover mottle virus (RCMV) middle component (M) RNA, we have synthesized an oligopeptide corresponding to the predicted carboxy-terminus of the RCMV counterparts of the cowpea mosaic virus (CPMV) 48K and 58K proteins. Using an antiserum raised against this synthetic oligopeptide, we have detected a 43-kDa protein in the 30,000 g pellet from extracts of RCMV-infected cowpea protoplasts. Immunogold cytochemistry further localized this protein to the plasmodesmata of RCMV-infected pea tissue. This subcellular location, taken together with other evidence, suggests that this 43-kDa protein has a role in the cell-to-cell spread of RCMV. PMID- 2596021 TI - SVLM21, a Sindbis virus mutant resistant to methionine deprivation, encodes an altered methyltransferase. AB - The replication of Sindbis virus (SVSTD) in cultured Aedes albopictus mosquito cells is sensitive to methionine deprivation. We have suggested from earlier work that this sensitivity is primarily because of a decreased pool of S-adenosyl methionine (ado met) and the resultant failure to methylate the 5' cap of the viral mRNAs. SVLM21, a strain of Sindbis virus derived in our laboratory from SVSTD by serial passage on mosquito cells maintained after infection in low concentrations of methionine, is resistant to methionine starvation. It was proposed that this adaptation to low methionine, and to the resultant low intracellular levels of ado met, reflected the accumulation of mutations which led to the generation of a viral RNA cap methyltransferase with an increased affinity for ado met. We report here kinetic data which distinguished the enzymes coded for by SVSTD and SVLM21. Using guanylylimidodiphosphate (GIDP) as the methyl acceptor, radioactively labeled ado met as the methyl donor, and lysates from infected BHK cells as the enzyme source, we calculated from our results that SVLM21 generated a methyltransferase with a Km for ado met 10-fold lower than that generated by either SVSTD or the related alphavirus, Semliki Forest virus. In addition, we found that BHK cells infected with SVLM21 generated higher levels of methyltransferase activity than did cells infected with SVSTD and that the SVSTD and SVLM21 enzymes differed with respect to their relative activities at elevated temperatures. We conclude from these results that the SVLM21 phenotype is associated with an altered methyltransferase and suggest that this is the basis of the resistance of SVLM21 to methionine deprivation. PMID- 2596023 TI - Nucleotide sequence analysis of the large (L) genomic RNA segment of Bunyamwera virus, the prototype of the family Bunyaviridae. AB - The complete nucleotide sequence of the large (L) genome segment of Bunyamwera virus has been determined from overlapping cDNA clones. The segment is 6875 nucleotides long and has a base composition of 29.8% A, 17.9% C, 15.4% G, and 36.9% U. Eighteen of the terminal 19 nucleotides at the 3' and 5' ends are complementary. In the viral-complementary (+ sense) RNA there is a single long open reading frame (ORF) from AUG at bases 51-53 to a UAG stop codon at bases 6765-6767; this ORF encodes a polypeptide of 2238 amino acids (MW 259,000), corresponding to the L protein which has been mapped to the L RNA segment by analysis of reassortants of Bunyamwera, Batai, and Maguari viruses. The amino terminal 46 amino acids of the L protein show strong homology (63% identity) with the amino-termini of ORFs predicted from limited sequence analysis of the L segments of La Crosse and snowshoe hare bunyaviruses. Comparison with the polymerase proteins encoded by other negative-strand viruses showed weak homology with part of the influenza virus PB1 protein, but no homology was detected with the other influenza virus polymerase proteins nor with the L proteins of arenaviruses, paramyxoviruses, and rhabdoviruses. At the 5' end of genomic (- sense) RNA there is an AUG-initiated ORF potentially encoding a protein of 14,700; the significance of this ORF is unknown at present. PMID- 2596022 TI - Mutated and hypermutated genes of persistent measles viruses which caused lethal human brain diseases. AB - Persistent measles viruses (MVs) causing lethal human brain diseases are defective, and the structure of several mutated matrix genes has been elucidated previously. The present study of four persistent MVs revealed a high number of differences from a consensus sequence also in other genes. Amino acid changes accumulated in the carboxyl terminus of the nucleocapsid protein and in the amino terminus of the phosphoprotein, but did not significantly alter these products, which are implicated in viral replication and transcription. The contrary is true for the envelope glycoproteins: In three of four cases, mutations caused partial deletion of the short intracellular domain of the fusion protein, most likely compromising efficient viral budding. Moreover, in the hemagglutinin gene of a strain showing strongly reduced hemadsorption, 20 clustered A to G mutations, resulting in 16 amino acid changes, were detected. This hypermutation might be due to unwinding modification of a part of the MV RNA genome accidentally present in a double-stranded form. Finally, we classified four lytic and seven persistent MV strains on the basis of their sequences. Surprisingly, the four lytic viruses considered belong to the same class. The persistent viruses form more loosely defined groups, which all differ from the vaccine strain Edmonston. PMID- 2596024 TI - The function of reovirus proteins during the reovirus multiplication cycle: analysis using monoreassortants. AB - When cultured cells are injected with mixtures of cores of two reovirus strains, a high proportion of reassortants are monoreassortants, that is, virus particles that contain one genome segment of 1 parent and 9 genome segments of the other. We have isolated two complete sets of monoreassortants, those that contain a single serotype 2 genome segment and 9 serotype 3 genome segments, and those that contain 1 serotype 3 genome segment and 9 serotype 1 genome segments. We have used the former set of monoreassortants (because reovirus serotypes 2 and 3 are less closely related than serotypes 1 and 3) to assess the effect of all 10 genome segments, or rather of the proteins that they encode, in controlling parameters of the reovirus multiplication cycle such as yield size, extent of viral ssRNA, dsRNA and protein synthesis, plaque size, and cytopathogenicity. Among the major findings are: proteins lambda 2, mu 1/mu 1C, and sigma 3 control yield size and extent of RNA and protein synthesis; proteins mu 2 and sigma 1 control severity of cytopathic effects; and proteins sigma 1, mu 1/mu 1C, and mu 2 control plaque size. Identification of monoreassortant phenotypes is useful for identifying which viral proteins are functionally involved at the various stages of the reovirus multiplication cycle. PMID- 2596025 TI - Improvements of the infectivity of in vitro transcripts from cloned cowpea mosaic virus cDNA: impact of terminal nucleotide sequences. AB - Full-length DNA copies of both B- and M-RNA of cowpea mosaic virus (CPMV) were constructed downstream from a T7 promoter. By removal of nucleotides from the promoter sequence, B- and M-RNA-like transcripts with varying numbers of additional nonviral sequences at the 5' end were obtained upon transcription with T7 RNA polymerase. The infectivity of the transcripts in cowpea protoplasts was greatly affected by only a few extra nonviral nucleotides at the 5' end. The addition of about 400 nonviral nucleotides at the 3' end did not have any effect. Using the most infectious transcripts, in 40% of the cowpea protoplasts replication and expression of B-RNA like transcripts were observed and in 10% of the protoplasts both B- and M-RNA-like transcripts multiplied. Moreover, cowpea plants could also be infected with these transcripts. Sequence analysis showed that the 5' terminus of the M-RNA transcripts and the 3' terminus of the B-RNA transcripts were completely restored during replication in plants, including a poly(A) tail of variable length. Swapping experiments have been used to identify an influential point mutation in the coding region for the viral polymerase of a noninfectious B transcript. This experiment demonstrates the potential of the optimized infection system for future analysis of virus-encoded functions. PMID- 2596026 TI - Analysis of sequences involved in cowpea mosaic virus RNA replication using site specific mutants. AB - Using a full-length cDNA clone of cowpea mosaic virus (CPMV) B-RNA from which infectious transcripts can be generated, we examined the influence of a sequence of 11 nucleotides, UUUUAUUAAAA, comprising the nucleotides 5883 to 5893 in the 3' noncoding region of B-RNA, on viral RNA replication. This sequence is not only present in B-RNA but also in M-RNA and represents the 7 nucleotides preceding the poly(A) tail and the first four A residues of the poly(A) tail. Replication of B RNA transcripts derived from a series of mutants in this region was tested in cowpea plants and protoplasts. Only mutant transcripts with minor modifications appeared able to replicate, which indicates that the region has a function in viral RNA replication. In addition, the results suggest the existence of a hairpin loop in this region. Those transcripts with deletions which disturb the putative hairpin structure have decreased specific infectivities. Mutant transcripts reversed stepwise to the wild-type sequence during replication in plants. This observation strengthens the idea that the sequence of 11 nucleotides has a function in viral RNA replication. PMID- 2596027 TI - Structure and transcription of the glycoprotein gene of attenuated HEP-Flury strain of rabies virus. AB - The mRNA-encoding G protein of the attenuated HEP-Flury strain of rabies virus was sequenced by the cDNA cloning technique. The G-mRNA was composed of 2059 nucleotides, with the coding region located from the 28th to 1602nd nucleotide, and was capable of encoding a polypeptide of 524 amino acids. Although the coding region was highly homologous (90% or more) to that of ERA and PV strains, the 3' noncoding region of the HEP virus G-mRNA was longer than that reported for other strains by some 400 nucleotides. The extra sequence was homologous to the long G L intergenic sequence of the PV viral genome. The HEP virus genome lacked the postulated polyadenylating signal (TG-AAAAAAAA) that should have been found just before the "long G-L intergenic region," which indicates that the long G-L intergenic region of the HEP virus is integrated into the preceding G gene, and is transcribed only as a portion of the G-mRNA molecule. In the ERA virus infected cells, however, two species of G-mRNA (1.9 and 2.3 kb long) were produced. The longer G-mRNA also contained the sequence complementary to the long G-L intergenic region and the shorter one did not. These findings suggest that two different poly(A)-tailing signals (one is present just before and another at the end of the long G-L intergenic region) work toward terminating the transcription of the ERA virus G gene and that the longer G-mRNA is produced as a readthrough product. PMID- 2596028 TI - Decreased levels of TMV coat protein in transgenic tobacco plants at elevated temperatures reduce resistance to TMV infection. AB - Transgenic tobacco plants that accumulate tobacco mosaic virus (TMV) coat protein (CP) are resistant to TMV infection under standard growth conditions. The amount of CP accumulated and the degree of resistance to TMV were found to be temperature dependent. Exposure to continuous high temperatures (30-35 degrees) results in a sharp decrease in the amount of CP within 6 hr with no further change for at least 6 days. Under these conditions the transgenic plants developed typical systemic disease symptoms when inoculated with TMV although disease development was delayed. Transgenic plants which were moved from 35 to 22 degrees accumulated the normal level of CP within several hours. Transgenic tobacco plants inoculated and held at 35/25 degrees day/night cycles retained resistance to TMV infection. The level of CP mRNA was constant at each temperature and was associated with polyribosomes. On the basis of these results we suggest that the low level of CP under elevated temperature is due to instability of the TMV CP. In contrast, TMV CP levels in transgenic tomato plants also dropped under elevated temperatures yet retained high resistance to TMV. PMID- 2596029 TI - Cell type specific expression and regulation of murine interferon alpha and beta genes. AB - The differential and cell type specific expression of various murine IFN alpha genes and IFN beta was examined by S1 nuclease protection assays in M-CSF cultured C57BL/6 mouse bone marrow macrophages and L929 fibroblasts. In Newcastle disease virus (NDV) induced macrophages, IFN beta, alpha 2, alpha 4, and alpha 1 mRNAs were the predominant species, whereas IFN alpha 6 and alpha 9 transcripts accounted for only 5% of total IFN alpha mRNAs. In L929 cells, only IFN beta, alpha 2, and alpha 4 genes were expressed efficiently following NDV induction and IFN alpha 9 mRNA was always below detectable level. Induction of macrophages with the synthetic inducer 10-carboxymethyl-9-acridanone resulted in small amounts of IFN alpha 2, alpha 4, and alpha 6 mRNAs and the IFN beta mRNA level was about 100 fold higher. Macrophages and L929 cells especially differed in the kinetics of IFN gene induction in that macrophages showed a much earlier transient expression of all IFN mRNA species. Additionally, IFN transcripts were degraded much faster in macrophage cultures than in L929cells. The IFN response of macrophages is thus characterized by a highly efficient control, providing a rapid onset and a rapid decline of IFN production, which limits release of IFN to a short time interval. PMID- 2596030 TI - Polyadenylation function and sequence variability of the long terminal repeats of the human endogenous retrovirus-like family RTVL-H. AB - The RTVL-H family of human endogenous retrovirus-like sequences consists of approximately 1000 "full-length" elements and at least as many solitary RTVL-H related long terminal repeats (LTRs). We have characterized cDNA clones from two human cell libraries (Hep-2 and normal peripheral blood) and have found three clones in which the AATAAA signal within the RTVL-H LTR has functioned to polyadenylate the transcript. In two of these cases the LTR has provided the polyadenylation signal for non-RTVL-H initiated transcriptional units. The DNA sequences of the LTR regions from these three cDNA clones are significantly different from a consensus LTR sequence generated from 10 genomic LTRs. In fact, two of these cDNA-derived LTRs, although closely related to each other, have a subregion within them which is not found in the genomic LTRs that have been analyzed. LTRs containing this subregion, termed type II LTRs, comprise approximately 25% of the total genomic LTR population. In stable DNA transfection experiments, both a type I and a type II LTR were able to donate a functional polyadenylation signal to a neomycin resistance gene. In LTR-positive placental cDNA clones, type II LTRs were found more frequently than expected from their genomic abundance. These findings suggest that RTVL-H LTRs may provide 3' processing signals for a variety of human RNAs. They also indicate that at least one distinct subpopulation of RTVL-H LTRs can be distinguished and suggest that this or other subpopulations may have different functional capacities in different human cells. PMID- 2596031 TI - Molecular cloning and sequence analysis of duck hepatitis B virus genomes of a new variant isolated from Shanghai ducks. AB - The genomes of duck hepatitis B virus (DHBV) from a brown duck (S5) and a white duck (S31) kept independently in Shanghai, China, were cloned and the complete nucleotide sequence of each virion DNA (DHBV-S5 and DHBV-S31) was determined. DHBV-S5 and DHBV-S31 were both 3027 bp in length and 6 bp longer than the other two DHBVs analyzed previously, DHBV16 and DHBV3. The genomes of DHBV-S5 and DHBV S31 encoded three long overlapping open reading frames designated as P, S, and C. A possible new open reading frame was found in a complementary strand of each viral genome, as 336 bp for DHBV-S5 and 306 bp for DHBV-S31, respectively. A pair of 3-bp insertions were found in the overlapping region of pre-S2 and P and so two amino acids were inserted in this region in DHBV-S5 and DHBV-S31. The nucleotide sequence variation between DHBV-S5 and DHBV-S31 (4.9%) was similar to that between DHBV16 and DHBV3 (5.6%), and less than the variations between either of these Shanghai clones and DHBV16 or DHBV3 (9.5-10.4%). The amino acid sequence was also conserved in the two Shanghai clones but showed group difference from DHBV16 or DHBV3. Thus these two independent Shanghai clones of DHBV showed geographical characteristics of genomic structure. PMID- 2596032 TI - Analysis of the function of viral protein X (VPX) of HIV-2. AB - To investigate the function of vpx, a gene in HIV-2 and SIV, but not in HIV-1, three site-directed mutants (pMX) were constructed from a functional proviral HIV 2 plasmid clone (pSE). Transfection of COS-1 cells with all three mutants as well as pSE gave rise to equivalent amounts of virus. Each virus could be passaged in H9 and CEM lymphoid cell lines, peripheral blood lymphocytes, and monocytes with equal efficiency and demonstrated similar cytopathic effects. Hybridization data with DAN from the infected cells demonstrated the presence of similar levels of viral sequences and the mutations in each of the MX-infected cell lines. Immunoprecipitation analysis demonstrated a 16-kDa VPX protein in cells infected with SE virus, as well as in the virus particles, but not in cells infected with MX viruses or the particles themselves. However, equivalent levels of gag and env proteins were demonstrated in all infected cells and virion preparations. These data suggest that VPX is dispensable for virus replication and cytopathicity. PMID- 2596033 TI - Transcription map of the B genome component of tomato golden mosaic virus and comparison with A component transcripts. AB - In a previous study, the bipartite genome of tomato golden mosaic virus (TGMV) was shown to be transcribed into at least six polyadenylated RNAs (G. Sunter, W.E. Gardiner, and D. M. Bisaro, 1989, Virology 170, 243-250). Two of these, a 1.3-kb complementary sense and a 0.9-kb viral sense transcript, were mapped to the B genome component of this geminivirus. The results of more detailed primer extension and S1 nuclease protection experiments presented here define the limits of the single transcription unit corresponding to the 0.9-kb RNA which spans the BR1 open reading frame (ORF). The data also demonstrate that complementary sense TGMV RNAs are more complex than indicated by our earlier studies. Analysis of the 1.3-kb BL1-specific RNA indicates that it is actually a family of distinct transcripts with different start sites. Three transcripts have 5' ends that map near the common region of DNA B and all of these start sites lie upstream of the BL1 ORF. Similar analysis of the 1.6-kb complementary sense AL1 RNA indicates that a complex set of transcripts also map to the analogous region of genome component A. Four transcripts have 5' ends that map near the common region but only one of these start sites is upstream of the initiation codon for the AL1 open reading frame (ORF). None of the transcripts appear to be processed. The possible significance of multiple transcripts in these regions of the TGMV genome is discussed, and the common region-proximal transcription units of the A and B genome components are compared. PMID- 2596034 TI - Effect of protein aggregation state on coat protein-mediated protection against tobacco mosaic virus using a transient protoplast assay. AB - To address the mechanism(s) of protection against tobacco mosaic virus (TMV) infection conferred by expression of the TMV capsid protein (CP) gene in transgenic tobacco plants, a transient protection assay has been developed. Introduction of either purified viral CP or virus inactivated by ultraviolet irradiation into tobacco protoplasts induced a transient protection to challenge virus introduced concomitantly or shortly thereafter. The transient protection was characterized and the effects of different aggregation states of TMV CP were tested in the transient assay system. Tobacco mosaic virus CP preparations composed largely of helical, virus-like, aggregates conferred a less transient protection against TMV and greater protection against a distantly related virus than did preparations composed primarily of smaller aggregates. PMID- 2596035 TI - In vitro transcription by cytoplasmic extracts from cells infected with African swine fever virus. AB - A cell-free system for the study of transcription of African swine fever virus (ASFV) mRNA was developed from cytoplasmic extracts of infected cells permeabilized with lysolecithin. Extracts prepared from infected cells early and late after infection incorporated [alpha-32P]UTP into acid-insoluble material that was resistant to DNase and sensitive to RNase. The incorporation was inhibited by actinomycin D but not by alpha-amanitin. The presence of the nuclei was not required. In vitro transcription was optimal at pH 7.9 and at concentrations of 100 mM NH4Cl, 5 mM magnesium acetate, and 250 microM MnCl2. Early infected cell extracts transcribed from endogenous viral DNA a set of RNAs similar in electrophoretic migration to that observed in intact infected cells. Late infected cell extracts seemed to be unable to transcribe new RNA species besides those transcribed early after infection. The activity of the extracts could be made dependent on exogenous templates by digestion with micrococcal nuclease. RNAs transcribed after addition of native or denatured viral DNA to nuclease-treated extracts were indistinguishable from those transcribed from endogenous viral DNA. Late infected cell extracts digested with micrococcal nuclease were also active in transcribing virus-specific RNA from p2SB21, a recombinant plasmid containing the SalI B fragment of ASFV DNA. PMID- 2596036 TI - Tobacco mosaic virus coat protein: an elicitor of the hypersensitive reaction but not required for the development of mosaic symptoms in Nicotiana sylvestris. AB - Specific nucleotide changes in the coat protein gene of tobacco mosaic virus (TMV) have been identified as responsible for the induction of the hypersensitive reaction (HR) in Nicotiana sylvestris. Each of these nucleotide changes resulted in amino acid substitutions in the coat protein. To determine if the altered viral RNA or the altered protein acted directly to elicit the HR, the coat protein translational starts were removed from full-length cDNA clones of the HR inducing mutant TMV 25 and the systemically infecting TMV U1 strain. Infectious transcripts of these altered genomes failed to induce HR in inoculated leaves of N. sylvestris. These free-RNA mutants moved poorly out of inoculated leaves and produced a systemic mosaic symptom 9 to 12 weeks after inoculation. Infectious viral RNA, from both mutants, was recovered from inoculated and systemic mosaic leaves. Western blot analysis of both inoculated and noninoculated leaves revealed the presence of TMV-encoded 126-kDa protein and the absence of coat protein for both mutants. This study demonstrates that the coat protein of TMV 25 is an elicitor molecule responsible for the induction of HR in N. sylvestris and that the TMV coat protein is not required for the development of systemic mosaic symptoms. PMID- 2596037 TI - trans-activation by the hepatitis B virus X protein shows cell-type specificity. AB - The hepatitis B virus X protein can trans-activate transcription from many viral promoters. We show here that this trans-activation is cell-type but not species specific, and that only a subset of promoters is trans-activated in any particular cell type. Furthermore, the T/t-antigens from simian virus 40 suppress this trans-activation. We hypothesize that the X protein acts via cellular factors which are phylogenetically conserved and developmentally regulated and whose effects are blocked by the T/t-antigens. PMID- 2596038 TI - Vital and health statistics. Current estimates from the National Health Interview Survey, 1988. AB - Includes estimates on incidence of acute conditions, episodes of persons injured, disability days, physician contacts, prevalence of chronic conditions, limitation of activity, hospitalizations, and assessed health status. PMID- 2596039 TI - Vital and health statistics. Trends in hospital utilization: United States, 1965 86. AB - This report presents statistics on the utilization of non-Federal short-stay hospitals based on data collected through the National Hospital Discharge Survey from 1965 through 1986. The survey is a national sample of records of discharged patients. Estimates are provided on demographic characteristics of patients discharged, selected conditions diagnosed and procedures performed, and by geographic region of the hospital. Measurements of hospital utilization include frequency, rate, percent, and average length of stay. PMID- 2596040 TI - [Optimization of the surgical work at a military polyclinic]. PMID- 2596042 TI - [Lung lesions in gunshot wounds and explosive mine trauma preceding the development of pneumonia]. PMID- 2596041 TI - [Treatment of outpatients at a polyclinic day hospital]. PMID- 2596043 TI - [An analysis of the acute pneumonia morbidity in servicemen and the work trends for its prevention and treatment]. PMID- 2596044 TI - [Qualitative parameters for combat training]. PMID- 2596045 TI - [The use of antikallikrein-antikinin preparations in emergency therapy]. PMID- 2596047 TI - [Rapid control over the functional state of the kidneys during long marches on foot across deserts]. PMID- 2596046 TI - [Basic radiation values and units for their measurement used in the practice of health inspection]. PMID- 2596048 TI - [The visual illusion problem in flight personnel]. PMID- 2596049 TI - [Quantitative EEG indices in sailors with various levels of success in occupational activities in extreme situations]. PMID- 2596050 TI - [Experience in organizing and conducting an epidemiologic surveillance of meningococcal infection]. PMID- 2596051 TI - [The combined treatment of patients with vascular diseases of the legs at a polyclinic day hospital]. PMID- 2596052 TI - [Potentials and prospects for the use of magnetic-laser therapy]. PMID- 2596053 TI - [The use of vacuum ophthalmodynamometry for assessing pressure in the cortical arteries of the brain]. PMID- 2596054 TI - [Sanative bronchoscopy and selective artificial pulmonary ventilation via the bronchoscope in adult respiratory distress syndrome]. PMID- 2596055 TI - [The role of the mononuclear phagocyte system in chronic diseases of the ENT organs]. PMID- 2596056 TI - [Leadership experience of oral antialcohol propaganda among the troops of a military district]. PMID- 2596057 TI - [Organizational and methodologic approaches to the design of information systems for the general hospital]. PMID- 2596058 TI - [Detection of basal-cell nevus syndrome in patients with multiple skin basiliomas]. AB - Medico-genetic examinations of 122 patients with multiple and/or early-onset basalioma revealed 5 cases of basal cell nevus syndrome. Clinical data on 5 probands and 3 first-degree relatives with the syndrome are presented. PMID- 2596060 TI - [Mast cell infiltration of the stroma and free heparin in the blood in breast cancer]. AB - The study included mast cell content assay in breast cancer stroma, free blood heparin measurement and its variation versus treatment and disease outcome. In clinically unfavorable cases, tumors displayed equal levels of mast cells whatever treatment procedure (surgery, chemotherapy + surgery). However, in patients with aggressive course, mast cell concentration decreased 3-fold following surgery whereas it rose significantly after combined therapy. In clinically favorable cases, free blood-heparin level was half the one in those with aggressive course. PMID- 2596059 TI - [Diagnosis and treatment of mesenchymal chondrosarcoma]. AB - Eight cases of mesenchymal chondrosarcoma (3 males and 5 females aged 15-65) are described. Morphological examination revealed in all cases biphasal tumor consisting of the chondroid tissue of varying maturity and undifferentiated tissue. Combination and complex treatment was given to 6 patients. In 4 cases, radiotherapy was carried out in combination with chemotherapy and local electromagnetic hyperthermia. Out of 8 patients, seven are still alive and are examined at 4 month - 11 year intervals (average of 39.7 months). One female patient died 12 months after the beginning of treatment. Combined and complex procedures should be recommended for treatment of such patients. PMID- 2596061 TI - [Study of DNA content using a flow cytometry method and steroid hormone receptors in breast cancer]. AB - DNA level measured by flow cytometry and estrogen and progesterone receptors assayed in tissue samples obtained from 85 malignant and 16 benign lesions of the breast. All the benign tumors revealed 2c DNA content and most of them were receptor-negative, while 74.1% of breast carcinomas displayed aneuploidy. Three patients (3.5%) had two lines of aneuploid cells. Many aneuploid tumors were receptor-negative. Preoperative radiation treatment (14-20 Gy) did not significantly influence the level of steroid hormone receptors in tumors. Estrogen receptor level was higher in menopausal patients than in premenopausal ones. PMID- 2596062 TI - [Immunomodulating activity of natural killers in patients with breast tumors using vasopressin and interleukin 2 in vitro]. AB - The study included 10 female donors, 12 patients with benign and 59 with malignant tumors of the breast at various stages before and after treatment. The immunomodulating effect of vasopressin and interleukin-2 on blood-natural killer functional activity was studied in vitro. Vasopressin dose of 4 x 10(-1) IU/5 x 10(5) cells exerted an immunosuppressive effect while 4 x 10(-5) IU/5 x 10(5) cells stimulated immunity. The stimulating effect of optimal interleukin-2 dosage (20-40 U/5 x 10(5) cells) on natural killer functional activity appeared 1.5-2 times higher than that optimal vasopressin dose (4 x 10(-5)/5 x 10(5) cells). Combined administration of the agents was not followed by increase in overall effect. Sensitivity of blood-natural killer cells in breast cancer patients to vasopressin and interleukin-2 depended upon clinical pattern, stage of tumor and treatment modality. PMID- 2596063 TI - [A mathematical analysis of immunologic indicators in dyshormonal dysplasia and breast cancer]. AB - Correlations between immunologic indexes in patients suffering dyshormonal hyperplasia (33), carcinoma of the breast (48) and healthy females (25) were studied. Rosette-formation test and its modifications were used to evaluate immunologic vigor. No significant differences were found between the quantitative and structural characteristics of immunologic vigor. General relationship between correlations involved in dyshormonal hyperplasia and cancer of the breast were identified. Increased frequency of correlations between paired characteristics was reliably established in patients as compared with healthy subjects; also multiple correlations between the indexes of different lymphoid subpopulations were increased. PMID- 2596064 TI - [Clinico-morphologic parallels in synchronous cancer of the endometrium and ovaries]. AB - A comparative study of 84 cases of endometrial and ovarian carcinoma showed clinical course of endometroid tumor to be more favorable than that of non endometroid one (five-year survival--72.5 and 8.2%, respectively). PMID- 2596065 TI - [Assessment of the efficacy of combined treatment of stage III throat cancer]. AB - It was shown that a preoperative course of radiotherapy in a total focal dose of 40 Gy could be easily tolerated by cancer patients without contributing to postoperative complications development. Survival in patients with stage IIIa tumors given a course of radiotherapy preoperatively was 23.81% higher than in those operated on for tumor at the initial stage. Survival in preoperatively irradiated patients with stage IIIb tumors was higher by 17.14%. PMID- 2596066 TI - [The role of conservative resection in surgical treatment of patients with lung cancer]. AB - The immediate and end results of 56 limited segmental resections of the lung (palliative--12 and radical--44) for cancer were studied. Postoperative mortality was 6.8% and five-year survival--50.0%. It is suggested that surgery for peripheral cancer without regional metastasis should be recommended for tumors under 2 cm in diameter in poor-risk patients. The procedure should be preferred for treatment of adenocarcinoma. PMID- 2596067 TI - [Active thermography in the diagnosis of breast cancer]. AB - Three procedures of active thermography were used in examination of 1301 patients with stage I-III breast tumors. The evaluation of their diagnostic effectiveness established their evident advantages over any method of passive thermography. Application of active procedures increased diagnostic accuracy by 9-15% and decreased the number of false negative results by 4-10%. PMID- 2596068 TI - [Use of a personal computer for storage and statistical processing of information on patients with breast cancer]. AB - The breast cancer data analysis system (BCDAS) was developed to be used in personal computers to enter, store and process data on breast cancer patients. It is a multi-purpose system adjustable to other applications. PMID- 2596069 TI - [Combined surgery in cancer of the proximal section of the stomach]. AB - The investigation showed combined surgery for cancer of the gastric cardia to be justified from the oncological point of view. Such intervention reaches out to the limit of radical treatment. However, combined surgery should not be performed unless there are substantial indications. Basic indications for excision or resection of an adjacent organ should be gastric tumor extension through organs and tissue or dissemination to the regional lymph nodes which cannot be radically removed unless surgery is performed on adjacent organs. PMID- 2596070 TI - [Prevention of postoperative complications in patients with stomach cancer using an antioxidant complex]. AB - The suitability of complex administration of antioxidants (vitamins C, E and A) for prevention of postoperative complications was assessed in a randomized study which included 197 cases of gastric cancer. The treatment was followed by a lowering of lipid peroxidation process. In a group of 95 patients who had received the drugs preoperatively, the postoperative complication rate dropped from 30.9 to 1.9%. PMID- 2596071 TI - [Treatment of patients with sarcoma of the uterus]. AB - The choice of treatment for uterine sarcoma should be determined by histological pattern and stage of tumor as well as by the patient's general condition. Operation should be withheld unless it is life-saving. The extent of surgery should vary from extirpation of the uterus with the appendages (leiomyosarcoma) to extended extirpation with pelvic lymphadenectomy for mixed mesodermal tumor, carcinosarcoma and endometrial stromal sarcoma. In the three latter cases, surgery should be followed by distant and/or endovaginal irradiation. Administration of such antitumor antibiotics as carminomycin and adriamycin assures a significantly longer survival in cases of recurrent and disseminated uterine sarcoma. PMID- 2596072 TI - [Assessment of the histologic type of Hodgkin's disease as a prognostic factor]. AB - The clinico-morphological data on 99 autopsied cases of Hodgkin's disease were analysed to assess the histological pattern of the disease as a prognostic factor. A correlation between the histologic pattern of the disease and lethality was established for the first 24 months after diagnosis verification. However, transformation of histological pattern was observed in 50% of cases. It is inferred that histological pattern of Hodgkin's disease can be used as a prognostic factor in planning schedule of treatment, changes in the histologic characteristics of pathological process being taken into account. PMID- 2596073 TI - [Long-term results of treating breast cancer]. PMID- 2596075 TI - [8th Congress of Internal Medicine. Tolboukhin, September 23-25, 1988. Proceedings]. PMID- 2596074 TI - [Synchronous primary-multiple cancer of the kidney, urinary bladder and prostate gland]. PMID- 2596076 TI - [Shortcomings and errors in the treatment of heart failure]. PMID- 2596077 TI - [Acute kidney failure resulting from incidents at birth--difficulties of treatment, complications and prognosis]. PMID- 2596079 TI - [The serum concentration of trace elements in chronic kidney failure]. PMID- 2596078 TI - [The treatment of patients with idiopathic membranous glomerulonephritis with cyclosporin A]. PMID- 2596080 TI - [A decrease in the basophilic granulocyte count of the blood during exacerbation of the idiopathic nephrotic syndrome]. PMID- 2596082 TI - [Alcoholic lesions of the digestive system]. PMID- 2596081 TI - [The potentials of radionuclide nephrography and renal scintigraphy in the diagnosis of chronic pyelonephritis]. PMID- 2596083 TI - [Acquired (nonfamilial) polycystosis in kidney patients undergoing conservative treatment]. PMID- 2596084 TI - [Diagnostic potentials of synovial puncture biopsy of the knee joint in nosologically unclassified arthritis]. PMID- 2596085 TI - [Therapeutic use of plasmapheresis in internal and skin diseases]. PMID- 2596086 TI - [Immunologic indices in patients with sepsis of unknown etiologic cause]. PMID- 2596087 TI - [Apheresis of low-density lipids in the treatment of hereditary hypercholesterolemia]. PMID- 2596088 TI - [Characteristics of acute respiratory poisoning by toxic gases]. PMID- 2596089 TI - [Determination of the concentration of immunoglobulins G, A and M and of the complement activity in patients with erysipelas]. PMID- 2596090 TI - [Immunodeficiency syndromes with involvement of the small intestine]. PMID- 2596091 TI - [Blood rheologic changes in patients with various clinical forms of ischemic heart disease]. PMID- 2596092 TI - [Blue sclera in iron-deficiency states]. PMID- 2596093 TI - [Interdisciplinary problems in nephrology]. PMID- 2596094 TI - [Alcoholic lesions of the liver]. PMID- 2596095 TI - [Prazosin in the treatment of arterial hypertension]. PMID- 2596096 TI - [Dynamic changes in indices of cardiovascular hemodynamics in patients with chronic obstructive lung disease]. PMID- 2596097 TI - [The prognostic significance of a prolonged electrical systole in patients with acute myocardial infarct]. PMID- 2596098 TI - [Arterial hypertension and its complications--a factor in the unfavorable course of kidney diseases]. PMID- 2596101 TI - [Transbronchial and transthoracic diagnosis of lung cavities]. PMID- 2596099 TI - [Prevention of bronchopulmonary infections with the Bulgarian immunomodulator respivaks]. PMID- 2596100 TI - [Therapeutic drug monitoring of theophylline in the serum and saliva]. PMID- 2596102 TI - [Mucociliary clearance measurement--a possibility for the early diagnosis of chronic nonspecific lung diseases]. PMID- 2596103 TI - [One- and two-dimensional echocardiography in the diagnosis of exudative pericarditis]. PMID- 2596104 TI - [Intubation and mechanical ventilation of patients with severe respiratory failure]. PMID- 2596105 TI - [Current problems of microbiological research on patients with lung diseases]. PMID- 2596106 TI - [The efficacy of therapeutic lavage in the combined treatment of suppurative lung diseases]. PMID- 2596107 TI - [New forms of follow-up and treatment of diabetics]. PMID- 2596108 TI - [The incidence and nature of diabetes mellitus in patients with bronchial asthma]. PMID- 2596109 TI - [The diagnostic value of the propranolol-glucagon test for somatotropin secretion]. PMID- 2596110 TI - [Endoscopic sclerosing therapy to prevent hemorrhage of esophageal varices in patients with portal hypertension (a 4-year study)]. PMID- 2596111 TI - [Gastroesophageal reflux--endoscopic and scintigraphic correlations]. PMID- 2596112 TI - [Fiber endoscopy in the diagnosis of acute hemorrhage of the upper digestive tract]. PMID- 2596113 TI - [Endoscopic retrograde cholangiopancreatography in the diagnosis of diseases of the biliary system and pancreas]. PMID- 2596114 TI - [The frequency of haptoglobin types in chronic liver diseases]. PMID- 2596115 TI - [The reinfusion of ascitic fluid into patients with liver cirrhosis and ascites resistant to drug treatment]. PMID- 2596116 TI - [Changes in the values of antithrombin III and other blood coagulation indices in liver cirrhosis without ascites and in the ascitic stage]. PMID- 2596117 TI - [Acute kidney failure in nontraumatic rhabdomyolysis (the myorenal syndrome)]. PMID- 2596118 TI - [The lipolytic activity of dermatophytes]. AB - Dermatophytes are able to crack the fatty acid molecule of polyoxyethylensorbitan monolaurate (Tween 20), polyoxyethylensorbitan monopalmitate (Tween 40), polyoxyethylensorbitan monostearate (Tween 60), and polyoxyethylensorbitan monooleate (Tween 80). The hydrolysis of this medium occurs due to lipolytical enzymes of dermatophytes. The liberated fatty acids bind up the calcium, which is added in the medium. They are visible as insoluble crystals around the colonies. PMID- 2596119 TI - [Does sodium hydroxide soda help in oral candidiasis?]. AB - The following results proof: in the case of Candida albicans-infection sodium hydrogen-carbonate-treatment does not work. PMID- 2596120 TI - [Dermatomycoses relevant to general practice and their treatment]. AB - Dermatomycoses probably form the biggest group in dermatological diseases. To an increasing extent even children and juveniles are affected. Choosing the right antimycotic, e.g. Cielopiroxolamine, with a broad spectrum and a high antimycotic activity in each localisation as well as good tolerability, will strongly influence therapeutic results. Whenever the dermatophytoses are deeply situated in the skin or cover large areas Griseofulvin should be used. The combination of the latter with a local antimycotic might shorten therapeutic therapy and might lead to a lower frequency of relapse. PMID- 2596121 TI - [Mycoses and AIDS]. AB - The number of patients with AIDS is still growing rapidly. The identification of opportunistic diseases requires special skills in microbiology. The methods for identifying and distinguishing between opportunistic fungi and pneumocystis carinii are introduced. PMID- 2596122 TI - [Prevention of candidiasis in at-risk patients]. AB - Colonisation by yeasts and invasive yeast-growth (candidosis, yeast-mycosis) increase whenever a patient's power of resistance is lowered. Early recognition of colonizing yeasts in a patient can be as important for his vital functions, as the therapy of the underlying disease will be. This seems to be quite complicated in many cases and often it is omitted by several reasons. An "easy to handle method" is a "rapid yeast culture". Blood-cultures and serodiagnosis can be added if held necessary. It is more important to find out, if there are few or many yeast-cells in a patient, than to count them. Hidden "yeast-nests" can in short time recruit eliminated yeasts. Too much sugar means too many yeasts as well. Anti-yeast-therapeutics have to be selected and dosed according to their characteristic qualities. PMID- 2596123 TI - Selected papers from the seventh annual Ella T. Grasso Memorial Conference. New Haven, Connecticut, November 15, 1989. PMID- 2596124 TI - Histologic and clinical characteristics associated with rapidly progressive invasive cervical cancer: a preliminary report from the Yale Cancer Control Research Unit. AB - Histologic and clinical characteristics associated with rapidly progressive invasive cervical cancer are presented in this preliminary report from a population-based study involving all patients in Connecticut diagnosed with cervical cancer from March 1, 1985. Rapidly progressive invasive cervical cancer, i.e., invasive cancer diagnosed within three years of a true negative Pap smear, is more likely to occur in younger women with high annual incomes (61 percent greater than $40,000) who report a greater frequency of benign gynecologic conditions (uterine leiomyomata, vaginitis) compared to a control cervical cancer group. These preliminary data suggest that as many as 35 percent of the rapidly progressive cervical cancers are likely to be adenocarcinomas. Because they are mostly endocervical in origin, they may not be detected cytologically if scrapers or cotton swabs are used to sample the endocervical canal. New cytologic screening techniques using brushes may identify these lesions earlier and should routinely be employed in cytologic screening for cervical neoplasia. The difficulty in early detection of this form of the disease requires that physicians rapidly assess patients with unexplained pelvic and lower abdominal pain, vaginal discharge, or abnormal vaginal bleeding since early recognition is the only chance for cure. Further analyses of this population of women will be made to identify additional risk factors when the study data are complete. PMID- 2596126 TI - Nifedipine in the treatment of hypertensive episodes in the coronary care unit. AB - The effectiveness of nifedipine for the treatment of acute hypertensive episodes in patients already taking chronic calcium-channel blocker therapy is unknown. We report our experience with 43 consecutive patients who received nifedipine for acute hypertensive episodes in the coronary care unit. Of the 43 patients (24 men, 19 women), 23 (53 percent) were taking chronic (greater than 2 mo) calcium channel blocker therapy. Nifedipine 10 mg capsules were chewed and swallowed with repeat doses given at hourly intervals if necessary. Target BP was 140/90 mm Hg, which was achieved in 31 of 43 patients (72 percent). In patients already taking calcium-channel blockers, target BP was achieved in 18 of 23 patients (78 percent). Response in patients not taking chronic calcium-channel blockers was observed in 13 of 20 patients (65 percent). Overall, adverse effects occurred in 16 of 43 patients (37 percent): 11 of 23 patients (48 percent) taking calcium channel blockers, and 5 of 20 patients (25 percent) not taking calcium-channel blockers. Nifedipine is equally effective in lowering BP in patients taking calcium-channel blockers as it is in patients not taking them. Although associated with a higher incidence of adverse effects in patients already taking calcium-channel blockers, these effects were not considered serious. Nifedipine is an effective agent in acute hypertensive episodes, even in patients receiving chronic calcium-channel blocker therapy. PMID- 2596128 TI - Communication of verbal information by community pharmacists. AB - Communication of verbal information on prescribed drugs is recognized as an important function of the pharmacist. This article describes and analyzes the communication behavior adopted by community pharmacists in the province of Quebec. Data were collected by means of two questionnaires mailed to a random sample of 634 community pharmacists. Percentage of prescriptions for new medications on which the pharmacists indicated they provide verbal information averaged 68.9 (SD 24.2). A majority of respondents indicated that they include information on the indication and mode of administration in more than 75 percent of their counseling episodes. However, on average, rare but serious adverse effects were less frequently discussed. The frequency of verbal communication was analyzed according to the pharmacist's gender, number of years since licensure, employment status, work setting, and perceptions of both professional and commercial dimensions of the pharmacist's role. Regression showed that perception of the professional dimension of the role, gender, workload, and floor surface of the pharmacy were related to provision of verbal information on new prescribed medications. PMID- 2596127 TI - Steroid-specific effects of ketoconazole on corticosteroid disposition: unaltered prednisolone elimination. AB - Ketoconazole inhibits the clearance of methylprednisolone by 60 percent and extends cortisol suppression beyond that produced by methylprednisolone alone. This study examined prednisolone pharmacokinetics and cortisol suppression in four healthy male volunteers following administration of prednisone 20 mg. Studies were performed with and without ketoconazole 200 mg po for six days. Blood samples were obtained serially over 24 hours and serum prednisone, prednisolone, and cortisol concentrations were determined by HPLC. Prednisolone clearance before and after ketoconazole therapy was not significantly different (160 +/- 38 vs. 148 +/- 23 mL/h/kg). In addition, no significant differences were found in mean residence time (5.03 +/- 0.69 vs. 6.18 +/- 1.77 h), terminal slope (0.23 +/- 0.03 vs. 0.19 +/- 0.05 h-1), or volume of distribution (0.79 +/- 0.11 vs. 0.84 +/- 0.12 L/kg). The ratio of cortisol area under the concentration versus time curve (AUC) 0-24 hours after prednisone administration to the AUC under baseline conditions was used as a measure of adrenal suppression. This ratio was not significantly different after prednisolone with and without ketoconazole (0.40 +/- 0.10 vs. 0.45 +/- 0.03). Renal excretion of prednisone and prednisolone was not significantly changed with ketoconazole. Based on this preliminary study, ketoconazole minimally alters prednisolone clearance in contrast to the significant ketoconazole-methylprednisolone interaction previously reported. PMID- 2596125 TI - Urinary gonadotropin fragment (UGF) measurements in the diagnosis and management of ovarian cancer. AB - UGF is a small peptide present in the urines and tissues of patients with gynecologic cancers. Published research (which, at present, mainly comes from our laboratory) on the general application of UGF as a tumor marker, and on its use in the diagnosis of ovarian cancer, is reviewed, and new studies on its use, alone and with CA125, in the management of patients with ovarian cancer, are presented. In 234 healthy women, 89 with benign disease, and 79 with ovarian cancer, UGF levels were above 3 fmol/ml (low cut-off) in 12 percent, 7 percent, and 82 percent, respectively, and above 8 fmol/ml (high cut-off) in 1.7 percent, less than 1.1 percent, and 59 percent, respectively. Similarly, 11 percent, 14 percent, and 70 percent, respectively, had CA125 levels above 35 U/ml (low cut off), and less than 1.9 percent, 1.2 percent, and 49 percent had levels above a 200 U/ml (high cut-off). Ideally, the higher UGF and CA125 cut-offs should be used for diagnostic applications, like differentiation of a benign from a malignant pelvic mass (false-positive rate: UGF, less than 1.1 percent; CA125, 1.2 percent), but raising the cut-offs diminishes sensitivities for malignancy (UGF, 59 percent; CA125, 49 percent). The populations detected by the two markers only partially overlap, however, so that, together, UGF or CA125 can identify 75 percent of malignant pelvic masses. Levels of UGF (cut-off, greater than 3 fmol/ml) and CA125 (35 U/ml) were also monitored in 30 women undergoing therapy for ovarian cancer. Clinical observations were reflected at each clinic visit by UGF alone in 67 percent, by CA125 alone in 57 percent, and by UGF and CA125 together in 87 percent of cases. While separately UGF and CA125 levels predicted 71 percent and 57 percent, together they forecast 86 percent of recurrent cancers prior to clinical manifestations. UGF and CA125 should be used together in the detection and management of ovarian cancers. PMID- 2596130 TI - Probucol in hypercholesterolemia. PMID- 2596129 TI - Carbamazepine toxicity precipitated by intravenous erythromycin. AB - The ability of erythromycin to inhibit the hepatic metabolism of carbamazepine causes carbamazepine toxicity. The severity of this drug interaction has been proposed to be related to the dose of erythromycin. The introduction of oral erythromycin produces a two- to fourfold increase in the carbamazepine serum concentration and the resultant toxic manifestations. Carbamazepine toxicity and a more marked increase in carbamazepine serum concentration were observed in a patient treated with intravenous erythromycin. PMID- 2596132 TI - Dinoprost in hemorrhagic cystitis. PMID- 2596131 TI - Antidepressants used in bulimia. PMID- 2596133 TI - Comparison of linear regression methods when both variables contain error: relation to clinical studies. AB - Five common linear regression methods were evaluated for their ability to determine the correct values of slope and intercept of a known function after random errors were added to x and y. The error variances were controlled to simulate research problems commonly studied by linear regression. The total error of each method was assessed by the absolute value of the bias in the estimate of slope. Whenever differences among methods were observed, the mean of the slope determined by two reciprocal techniques performed as well as or better than orthogonal regression, regression of y upon x, or x upon y. All the methods studied appeared to perform equally well when x and y errors were heteroscedastic or when the data set was small (n = 7). Regression of y upon x was equal or superior to other methods when n = 7 or n = 20 and y and x errors were homoscedastic. When the data set was large (n = 50) and the error in x greater than that in y, the standard method (regression of y upon x) was inferior to all other methods. It is suggested that linear regression by the traditional method of y upon x (a method present in many hand-held calculators) is appropriate in the majority of clinical situations, but when n is large and errors in x are much larger than those in y, orthogonal regression or the averaging method may be preferable. PMID- 2596134 TI - Pharmacotherapy. Part I. A new pharmacy specialty. PMID- 2596135 TI - Clinical pharmacy education in new England: a report of the Whispering Pines Conference. AB - Clinical pharmacy practice as it relates to the future of the pharmacy profession has been examined at Hilton Head in 1985 and at regional conferences throughout the U.S. between 1986 and 1988. However, clinical pharmacy education and its role in the future of the profession had not been the focus of this type of "futuristic" conference. In 1988, the clinical pharmacy faculties from the four colleges of pharmacy in New England met to discuss the "Directions for Clinical Pharmacy Education in New England." Through a series of workshops, and stimulated by challenges from keynote speakers, the participants focused on the current status of clinical pharmacy education in New England, the barriers to change, and the strategies required to accomplish these changes. Consensus on prioritization of changes and their strategies was reached, and those that could be implemented in the near future were identified. Since the conference, changes have occurred and the professional networking that began at the conference has continued. This paper is a summary of the proceedings of this conference. PMID- 2596136 TI - Are you an academician? PMID- 2596137 TI - Effect of renal failure and hemodialysis on aminocaproic acid plasma concentrations. PMID- 2596138 TI - Gentamicin pharmacokinetic changes related to mechanical ventilation. PMID- 2596139 TI - Psychotropic drug use in institutionalized people with mental retardation. PMID- 2596140 TI - Cost of liver transplant treatment. PMID- 2596142 TI - Nurturance--for one, for all. PMID- 2596143 TI - Comment: nimodipine in treatment of subarachnoid hemorrhage. PMID- 2596141 TI - Contrast media adverse reactions. PMID- 2596144 TI - Comment: doxorubicin extravasions. PMID- 2596145 TI - Comment: stability of caffeine injection. PMID- 2596146 TI - [Osteochondrosis dissecans of the talus. Results of a follow-up study]. AB - 26 of 38 surgically treated patients with Osteochondrosis dissecans of the talus underwent a follow-up-examination 4 years and 7 months in average after surgical treatment. Mechanical reasons seem to be one of the most common etiological factors. Sport activities with sprained ankles or recurrent micro-trauma of the ankle joint could be found as one of the most anamnestic answers. Most of the operatively treated patients showed a good postoperative result (congruent to 70%). The success of operation seems to be more dependent on the age of the patient than on the stage. Although signs of osteochondrosis could be seen long time postoperatively this disease leads to an osteoarthrosis only in a few cases and this seems to be more dependent on the age of the patient than on the stage. Because there is no randomised and prospective study comparing operative and non operative treatment no exact stage dependent recommendation can be given whether the treatment should be done conservatively or surgically. PMID- 2596147 TI - [Helal's metatarsal osteotomy. Indication and technic with reference to shape and function of the foot]. AB - Metatarsal osteotomy according to Helal is a successful method of treating metatarsalgia. Using this method, 72% of our patients, followed up between 1974 and 1986, (114 patients with a total of 336 osteotomies) were relieved of pain, the result depending on the patients' age. On reviewing the unsuccessful results using pedobarographic measuring, the major part of failures was due to an unequal distribution of weight on the forefoot. Two main types of faulty weight-bearing were stated: 1. Excessive weight-bearing on non-osteotomized adjacent metatarsals (domino-effect). In concern of the overall-result no difference could be found between cases with routine osteotomy II-IV and ones with single or double osteotomy. 2. Excessive weight-bearing on the complete fore-foot as a consequence of missing support by contracted metatarsophalangeal joints. When planning an operation, the length of all metatarsals in relation to each other, as well as the mobility of the toes should therefore be taken into consideration. PMID- 2596148 TI - [Follow-up following Lelievre's method of metatarsal head resection]. AB - From 1975 to 1987 on 107 cases of severe deformities of the forefoot a resection of the metatarsal heads according to the method of Lelievre was performed. As to the success of this method special features of this operation and especially the requirements of postoperative treatment will be explained. Possible complications of healing will be detailed. The procedure of resecting the heads of the metatarsal bones according to Lelievre seems to be recommendable in order to prevent immovability, especially in case of advanced inflammable alterations of the joints in the forefoot. PMID- 2596149 TI - [Caudal regression syndrome]. AB - It is reported about a young girl with congenital agenesis of the os sacrum, a congenital platfoot and a luxation of the left hip. These congenital malformations can be found in children born to diabetic mothers. PMID- 2596150 TI - [Partial spinal aplasia]. AB - The partial aplasia of the spine is a rarely seen syndrome. Describing 6 cases their clinical and radiological appearance is shown. With respect to the 4 cases mentioned in the literature until now one can distinguish 4 types. The differentiation between the partial aplasia of the spine and the syndrome of caudal regression is discussed. PMID- 2596152 TI - [Stability analysis of various forms of fusion of the lumbar vertebrae using a computer simulation model]. AB - To analyze mechanical properties of a lumbar functional unit a mathematical simulation model was developed. Using this model in different lumbar fusions immediate postoperative and secondary stability was analysed. Stability of different interbody and posterior fusions was compared looking at different techniques of operation an instrumentation. The calculation showed best results in the combination of posterolateral fusion with interspinal distraction or transpedicular screw instrumentation. These showed well-balanced load carrying properties primarily and high secondary stability. PMID- 2596151 TI - [Differentiated surgical and conservative treatment of spondylitis and spondylodiscitis]. AB - In the time from 1980 to 1987 58 patients underwent a conservative or operative treatment of spondylitis and spondylodiscitis according to the individual clinical and radiological features. In early or moderately advanced stages of the disease conservative therapy was performed. Under bedrest and antibacterial or tuberculostatic drug therapy bony fusion of the affected vertebral bodies was achieved in 50% of the pyogenic cases. In tuberculous spondylitis fusion rate was 83%. Persistent septic changes, progressive neurological symptoms and gross vertebral damage are indications for surgery. In those cases removal of the focus and intercorporal spondylodesis was performed. Bony union occurred in every cases. At follow-up examination, 3 years after the onset of therapy on an average, 42 patients had no complaints according to the vertebral column. As the results of our study show spondylitis and spondylodiscitis should according to the clinical and radiological features be lead to a differentiated operative or conservative treatment. Then good clinical results are to be supposed. PMID- 2596153 TI - [2 cases of humeral head osteolysis of unknown origin]. AB - Taking in account the medical history, the clinical and radiological presentation and the intraoperative and histological findings, two cases of osteolysis of the humeral head of unknown origin are discussed. After exclusion of underlying concomitant diseases a traumatic etiology seemed to be the most probable explanation although in both cases a trauma was denied by the patients. We are unaware of any similar cases published in the literature. PMID- 2596154 TI - [Malignant hemangiopericytoma--a soft tissue and bone tumor]. AB - Hemangiopericytomas are very rare tumors that mostly develop in the soft tissues. In rare cases, however, they may occur as primary bone tumors which are extremely rare. In case of such an intraosseous tumor, a bone metastasis of such a soft tissue sarcoma must be considered first and has to be excluded. In a 62 year old female, a hemangiopericytoma of the left femoral neck was diagnosed that had induced a pathological bone fracture. A resection of the femoral head and neck was performed. Anamnestical investigations, however, have shown that 4 years before, such a tumor of the pelvic soft tissues was removed. Thus, the lesion of the femoral neck had to be classified as bone metastasis of a malignant hemangiopericytoma. It has to be emphasized that this special tumor always shows a questionable prognosis and, by histological investigations, it cannot be decided if we are dealing with a benign or malignant tumor growth. Diagnostic managements and clinical problems with hemangiopericytomas are discussed in detail. PMID- 2596155 TI - [Polychrome sequential labeling of subchondrial bone tissue in early and advanced stages of gonarthrosis in male STR/IN-mice]. AB - Polychrome sequential labeling is used to study the dynamic of subchondral bone sclerosing during developing osteoarthrotic cartilage lesions in knee joints of male STR/1N-mice. The applied technique gives detailed information about site and time of new bone formation in the subchondral tissue using four different colored vital markers. Whereas control animals show regular bone deposition with a circumferential, concentric arrangement of fluorochromes along the various trabeculae, STR/1N-mice with osteoarthrotic cartilage lesions displayed fluorescence bands arranged eccentrically around the marrow cavities always pointing towards the cartilage lesions. The results also demonstrate, that the linear separation between the first label and the anatomic surface of the bone marrow cavity varies considerably in the individual experimental groups. Compared to control knee joints, which show appositional bone growth rates of 25 to 50 microns per 70 days, osteoarthrotic mice reveal increased bone growth rates during developing osteoarthrosis. In early osteoarthrotic cartilage lesions distances between the individual bands are distinctly larger in comparison to distances in advanced lesions. In both cases the rate of appositional bone growth exceeds bone formation in control animals 3 to 4 times. PMID- 2596156 TI - [Comparative animal experiments on tissue compatibility and measurement of radioactivity of various roentgen contrast media]. AB - In a comparative study the tissue reaction of several X-ray contrast materials was examined by subcutaneous and intraperitoneal application on rats. There were tested Bariumsulphate (BaSO4) and three Zircondioxyde (ZrO2) samples of several manufactures (cubic and monocline ZrO2-Feldmuhle; Optipur-Merck). In the histologic evaluation no inflammatory signs could be seen. In case of BaSO4 the tissue reaction was more distinct than in the ZrO2 samples. Within the tested ZrO2 samples the differences were small; the cubic ZrO2 showed the slightest, the monocline one the relatively strongest cellular reaction. We also measured the radioactive emission by the contrast media. Here the monocline and--first of all- the cubic ZrO2 showed an alarming radioactive emission (radium 3000-11,500 Bq/kg). Only the Optipur (Merck) was free of radiation and can so be recommended for human implantation. Also the BaSO4 had no measurable radioactive Emission. Therefore only these two X-ray contrast media can be recommended for human implantation. PMID- 2596157 TI - [Assurance and proof of satisfactory and complete information]. AB - To prevent unjustified blame and claims enforced by patients, is necessary to prove evidence of an indisputable and complete preoperative information. With the help of our developed software it takes little effort to satisfy the given demands. PMID- 2596158 TI - [The results of the scientific research of the Division of Physiology of the Academy of Sciences of the USSR in 1988]. PMID- 2596159 TI - Twenty-five years of renal trauma at a teaching hospital. AB - In a study of 535 patients with renal trauma admitted to the Medical College of Virginia Hospitals from 1962 to 1988, the authors found indications of a decrease in the rate of total nephrectomy in patients with blunt trauma, due in part to advances in diagnostic technology. In the cases of gunshot wounds, however, a persistently high rate of nephrectomy prevailed, reflecting, the authors believe, the proliferation of increasingly lethal weaponry. PMID- 2596160 TI - Endoscopic injection therapy for acute upper GI bleeding. AB - In summary, we have found this technique to be useful in patients in whom coagulation therapy is not possible or effective. It must still be considered a technique which is undergoing evaluation. Prospective randomized trials comparing this therapy with other currently available therapies such a electrocoagulation, laser and conservative management must be completed to firmly define its place in treatment strategy for acute upper GI bleeding. PMID- 2596161 TI - Long-time nursing school teacher favors both diploma, degree programs. PMID- 2596162 TI - Cites role of psychiatrists in impaired physicians program. PMID- 2596163 TI - Current status of cochlear implants in adults, children. PMID- 2596164 TI - "The best there is anywhere, and the credit is ours!". PMID- 2596165 TI - Physician's guide to the Natural Death Act. PMID- 2596166 TI - [Inger Ohlsson: independent nurse in community health care for the aged. Interview by Monika Trozell]. PMID- 2596167 TI - [Pioneering in Graberget: nursing diagnosis changes our job]. PMID- 2596168 TI - [Nursing diagnosis facilitates individual care]. PMID- 2596169 TI - [What is needed when one wants to work in the USA?]. PMID- 2596170 TI - [Disinfection operator and nurse--Lena is for traditions to continue. Interview by Britta Nillson]. PMID- 2596171 TI - [Vasteras decentralizes--profession keeps entirely out of it]. PMID- 2596172 TI - [Spinal cord injuries. Many divisions in special department]. PMID- 2596174 TI - [Incontinence and disposable pants]. PMID- 2596173 TI - [Rheumatoid arthritis. Artificial joints alleviate pain]. PMID- 2596175 TI - [Porphyria. Fasting and drugs threaten health status of porphyria patients]. PMID- 2596176 TI - [SHSTF advocates take responsibility for all problems]. PMID- 2596177 TI - [Knowledge and attitude do not agree: "HIV education should change". Interview by Monika Trozell]. PMID- 2596178 TI - [We visited 2 unisexual courses. Women or men in the SHSTF--does it have any significance?]. PMID- 2596179 TI - [We must invest in female leadership!. Interview by Kaj Nyman]. PMID- 2596180 TI - [Nurse anesthetist Inga works in Thailand. Here I know myself and my needs. Interview by Ase Ottosson]. PMID- 2596181 TI - [PUFF project which enhances pleasure in work]. PMID- 2596182 TI - [Rita Fahrner, San Francisco: how to counsel men and women with AIDS about becoming pregnant?. Interview by Anna Lena Rngarp]. PMID- 2596183 TI - [Women have their own perception of time. Nursing cannot take place according to male time tables. Interview by Barbro Blomberg]. PMID- 2596184 TI - [Sudden death: surgical aspects]. AB - The article deals with one of the least studied aspects of cardiac surgery: better approaches to managing patients at risk of sudden death. Sudden death due to the sick sinus syndrome commonly occurs in the elderly. In the Wolff-Parkinson White syndrome, ventricular fibrillation is possible in concomitant atrial fibrillation and high conduction along the Kent bundle. The risk of sudden death is particularly high among patients with ventricular tachycardia. This is most vividly manifested in coronarogenic tachycardia. Patients with allorhythmias and postoperative tachycardia are at high risk. Surgical methods and operative results are discussed. PMID- 2596185 TI - [The surgical treatment of congenital heart defects in neonates and infants without using invasive study methods]. AB - Echocardiographic analysis of 328 closed operations for aortic coarctation, patent ductus arteriosus, and congenital heart disease of the blue type with lower pulmonary flow in infants of the first year of life revealed diagnostic errors in 6 (2%) patients, this resulting in death of two patients. Surgery for congenital heart disease, which is based on the echocardiographic data without invasive diagnostic methods, requires proper patient selection. Quantitative two dimensional echocardiography allowed for higher accuracy of the preoperative diagnosis. Introduction of Doppler echocardiography made it possible to perform successful operations with assisted circulation in 16 patients for ventricular septal defects, atrial septal defect, transposition of great arteries, atrioventricular communication. PMID- 2596186 TI - [The use of personal computers in the angiocardiometric evaluation of the pulmonary artery in complex congenital heart defects]. AB - Application of personal computers in angiocardiometric assessment of the pulmonary artery in such congenital heart diseases as Fallot's tetralogy and total transposition of great vessels made it possible to set up a convenient data bank allowing one to store numerical and textual information, conventionalized drawings of pulmonary arteries showing the degree and location of stenosing lesions and color-marked data on surgically significant constrictions. The system has a rich visual presentation of data and allows for convenient and quick search and processing of information (including the use of standard statistic, graphic, and other present-day packages of analysis and presentation of medical information). PMID- 2596187 TI - [Acute disorders of the blood circulation and cardiac insufficiency following open heart surgery]. AB - General theoretical aspects (classification of circulatory disorders and heart failure) and results of research into specific subdivisions of cardiovascular and respiratory system pathology in cardiac surgical patients are discussed. The material is aggregated by the applied clinico-mathematical approach that has been developed and introduced into clinical practice in the recent 15 years at the Bakulev Institute of Cardiovascular Surgery. The extension of the clinico mathematical approach onto the intraoperative control and analysis of the patients' status, assessment of the anaesthetic administration and cardioplegic protection is first overviewed. PMID- 2596188 TI - [Quantitative evaluation of hypoplasia of the heart ventricles and its significance for heart surgery]. AB - The quantitative anatomy and morphology of hypoplastic ventricles were studied in 28 afflicted hearts (15 with left ventricular hypoplasia, 13 with right ventricular hypoplasia). The control comprised 10 normal heart specimens. All the 38 specimens were studied morphometrically; this was complemented with angiocardiometry and ventricular volume estimations in diagnosing right ventricular hypoplasia. Based on the study results, the morphometric criteria of ventricular hypoplasias and their variant forms were established. The linear characteristics were found to be informative enough both in hypoplasia diagnosis and in its degree assessment. To choose a therapeutic method, two degrees of right ventricular hypoplasia were distinguished. Radical correction aimed at eliminating concomitant conditions was found to be feasible and performed in 27 patients with moderate right ventricular hypoplasia. PMID- 2596189 TI - [Risk factors in Fontan's operation]. AB - The results of Fontan's procedure performed in 51 patients with various congenital heart defects were analysed. The procedure was found to have the following risk factors: the total lung resistance is above 4 mu/m2, the ejection fraction of the arterial ventricle, under 55%, serious concomitant heart defects, and additional surgical procedures that increase the scope of surgical interventions. The best results were obtained after creating a valveless atriopulmonary anastomosis; the poorest results were associated with a right atrium-pulmonary trunk anastomosis possessing its own valve. PMID- 2596190 TI - [Experience in the use of the Mustard operation in the surgical treatment of transposition of the great vessels]. AB - In the 1980-1988 period, Mustard's operation was used to treat transposition of great vessels at the Department of Younger Children, A. N. Bakulev Institute of Cardiovascular Surgery. Seventy nine patients were operated on: 56 with simple transposition, 9 (16%) patients died; 23 with complex transpositions of great vessels (18 with concurrent ventricular septum defect, 5 with Taussig-Bing's disease), 5 (22%) patients died. Rhythm disturbances and obstruction of the venae cavae were most common postoperative complications. Six patients underwent Mustard's operation with closure of ventricular septal defect. In 18 patients this operation was performed as a palliative procedure due to high pulmonary hypertension. Lung biopsy showed the majority of patients with concurrent transposition and interventricular septal defect to have grade III-IV changes (by Hit-Edwards' classification) in the pulmonary vessels. Long-term hemodynamic studies showed good effect of palliative Mustard's operation. PMID- 2596191 TI - [What should be the shape of extracardiac conduits?]. AB - Studies of the hemodynamic features of the blood flow in extracardiac conduits allow for a grounded and aimed approach to the prosthesis design. The lack of interrelationship between the duct geometry, the flow pattern, and the heart anatomy is one of the reasons for the existing conduits inadequacy. Here is proposed a confuser conduit model providing a stable uninterrupted flow. Development of a hemodynamically optimal type-size series of conduits would allow one to reduce the incidence of complications resulting from inadequate prosthesis design. PMID- 2596192 TI - [Principles of the diagnosis and intensive therapy of right ventricular insufficiency in patients following radical correction of Fallot's tetralogy]. AB - Examination of 107 patients that had undergone radical correction of tetralogy of Fallot using computer monitoring and mathematical modelling of circulation showed that right-ventricular failure was characterized by reduced cardiac output, high central venous pressure at relatively low left-ventricular pressures, high PV-PLA gradient at low pumping function of the right ventricle. An increase in the volume load in right-ventricular failure may lead to suppressed pumping function of the right heart. Thus, infusion therapy should be administered in relation to the PV-PLA gradient and its changes with increased adrenomimetic doses. Replacing assisted ventilation by spontaneous breathing should be accomplished in these patients using the technique of intermittent forced lung ventilation which is most optimal. PMID- 2596193 TI - [Clinical characteristics of the Soviet low-profile heart valve prostheses EMIKS and LIKS]. AB - The present work is devoted to the clinical assessment of the Soviet-made cardiac valve prostheses 'EMIKS' and 'LIKS'. From 1983 to May 1, 1988, 632 prostheses were implanted to 508 patients. A group of 348 patients were assessed: 139 after mitral (M) replacement, 130 after aortal (A) replacement, and 79 after mitral aortal (M+A) replacement. Hospital mortality rate was: in M group--4.3 per cent, in A group--5.3 per cent, in M+A group--8.8 per cent. Survival rate on the fifth postoperative year was: in M group--89.5 +/- 9.2 per cent, in a group--90.0 +/- 4.2 per cent, in M+A group--91.0 +/- 6.2 per cent, the stability of the good results being 85.5 +/- 7.2, 79.5 +/- 6.2, and 75.0 +/- 9.1 per cent, respectively. At year 5 of the follow-up, patient numbers without thromboembolic complications amounted to 95.0 +/- 4.7 per cent in M group, 95.5 +/- 4.2 per cent in A group, and 85.0 +/- 9.1 in M+A group. 95.1 per cent patients belong to functional classes I and II. In mitral replacement, the mean 'EMIKS' gradient was 4.2 +/- 0.58 mm Hg, the 'LIKS' one--4.58 +/- 0.62 mm Hg. Intravascular hemolysis was not observed. The 'EMIKS' and 'LIKS' prostheses match the models produced in other countries. No significant differences between the two models were found. PMID- 2596195 TI - [Dissecting aneurysms of the descending thoracic and abdominal aorta (current classification and surgical tactics)]. AB - Results of clinical studies and surgical treatment of patients with dissecting aneurysms of the descending thoracic and abdominal aorta are discussed. A new modification of the clinicoanatomical classification of this aortic disease is proposed with the emphasis on the possibility of (1) retrograde extension of the pathological process into the aortic arch with primary intimal rupture in the descending thoracic segment, and (2) multifocal aortic lesion, a combination of dissecting aneurysm and true discrete aneurysm of the unaffected aortic portion. The possibility of performing various types of one-stage and stage-by-stage reconstruction of the descending aorta depending on the degree and extension of dissection is shown. PMID- 2596194 TI - [Surgical tactics in dissecting aneurysms of the ascending aorta]. AB - The aspects of surgical tactics in management of dissecting aneurysms of the ascending aorta are analysed in relation to the disease etiology, the anatomical pattern of the aortic root, presence of attending aortic insufficiency, and dissection extension. Based on the experience of 32 operations (March 1979- February 1988), it is concluded that the abnormal type must be the best criterion for choosing the surgical technique. In dissecting aneurysms due to aortic wall degeneration, Bentall-De Bono and Cabrol's modifications are preferable. In dissecting aneurysms of atherosclerotic origin, the boundary of the proximal extension of dissection should be taken into account. When the dissection extends into the aortic root, the operation using a valve-containing conduit with reimplantation of the ostia of the coronary arteries is feasible. If the aortic root is not involved, isolated prosthesis of the ascending aorta or separate prosthesis of the aortic valve and ascending aorta may be performed depending on the presence of aortic failure. PMID- 2596196 TI - [Automated case histories in a cardiac surgery clinic (5 years' experience of use)]. PMID- 2596197 TI - Cancer incidence and mortality in Europe. PMID- 2596198 TI - [The occurrence of Clostridium difficile in fecal samples of dogs and cats]. AB - Fecal samples of 150 dogs and 175 cats originating from different veterinary practices were investigated for assessing the occurrence of Clostridium (Cl.) difficile by using a selective medium for cultural isolation. From dogs without enteric symptoms 7 (9.3%) of 75 samples were positive for Cl. difficile, with 2 strains being cytotoxic for bovine embryonic lung fibroblast cells, which could be neutralized by Cl. difficile-antitoxin. In samples of 75 dogs with enteric symptoms Cl. difficile could be isolated in 2 cases (2.7%). In cats 9 (9%) of 100 fecal samples deriving from animals without enteric symptoms contained Cl. difficile, while in 75 cats with enteric symptoms, the isolation rate was 6.7% (5 strains). Of either group only 1 Cl. difficile-strain showed cytotoxicity for tissue culture. The results of this study allow to conclude, that in contrast to the significance for man Cl. difficile is neither for dogs nor for cats an important enteric agent. However these pets can harbour and shed strains of Cl. difficile, even cytotoxigenic ones, in faeces. In view of these findings the possibility of occasional human infections by household dogs or cats needs attention and further investigation. PMID- 2596199 TI - In vitro proliferative and cytotoxic responses of PBL from Theileria annulata immune cattle. AB - Peripheral blood lymphocytes were isolated from healthy calves and were subsequently infected with sporozoites of Theileria annulata in vitro. The infected cells were passaged for 50 times and thereafter inoculated into animals from which they were previously isolated. Within 4-5 days, schizont-containing cells were demonstrable in the lymph nodes of all animals. Few days later, merozoites were detected in erythrocytes. A slight decrease in the counts of lymphocytes and leucocytes was also found. After 2 months these animals and a group of uninfected calves were heavily infected by tick-infestation and showed severe symptoms of theileriosis with 60% schizont-containing cells in the lymph nodes and a parasitaemia of about 35%. Because of the severity of the infection, all control calves were treated with Halofuginone. In contrast, the initially immunized cattle (by inoculation of culture cells), survived the infection without chemotherapy. Less than 10% of their lymph node cells contained schizonts, whereas less than 1% of their erythrocytes were found to be infected with merozoites. In all immunized animals, specific cytotoxic PBL, with the capacity to lyse autologous but not allogeneic infected cells, were demonstrated. In addition, a population of PBL were found to be able to inhibit the growth of T.annulata-infected culture cells in vitro. However, in comparison to PBL of immune animals, PBL of acute infected calves were superior in their capacity to inhibit the proliferation of schizont-containing cells. In mixed lymphocyte reactions, T. annulata-infected cells could induce a more pronounced proliferative response in PBL from immune than in PBL of uninfected animals. PMID- 2596200 TI - Monoclonal antibodies reacting specifically with Francisella sp. AB - Twenty two hybridoma strains producing monoclonal antibodies against Francisella tularensis ATCC 6223, var. tularensis, were characterized. In an enzyme-linked immunosorbent-assay (ELISA) using formaldehyde fixed bacteria as antigens, neither cross-reactions with six different Brucella spp., with Yersinia enterocolitica 0:9 nor with two biotypes of Yersinia pseudotuberculosis could be detected. The antibodies gave comparable titres with the three strains of F.tularensis tested. ELISA binding studies indicated that fifteen of the antibodies bound with high affinities to their epitopes of the three Francisella strains, while the others each seemed to bind with low affinity to at least one of the antigens. Immunoblot analysis showed that six of the antibodies were directed to epitopes on the core moiety of the lipopolysaccharide molecule, while the other 16 antibodies bound to O side chain components. PMID- 2596201 TI - Morbillivirus infection of seals (Phoca vitulina) during the 1988 epidemic in the Bay of Heligoland. I. Mode, frequency and significance of cultural virus isolation and neutralizing antibody detection. AB - From 16 (14%) out of 112 dead or euthanized seals originating from wildlife and seal orphanages phocine morbillivirus was isolated. The majority of viral isolates in cell cultures was obtained from lung homogenates of 15 out of 71 free ranging seals (21%). The virus was isolated by longterm cultivation in roller cultures of seal kidney cells. The phocine morbillivirus was detected by typical cytopathogenic alteration and by peroxidase-linked antibody (PLA) assay, respectively. A neutralization test based on PLA was used for antibody detection in seals using a canine distemper virus (CDV) strain and in parallel one of the phocine morbillivirus isolates. All sera tested were proven to contain neutralizing antibodies of higher titres against the latter virus than against the CDV strain. Several seals furnished morbillivirus isolates and at the same time exhibited neutralizing antibodies of low to medium titres. No viral isolates were obtained from the majority of sick animals with moderate to high neutralizing titres (greater than 1/1,000). The significance of these findings is discussed in relation to the cause of the mass mortality amongst seals observed in 1988 in the Bay of Heligoland. PMID- 2596202 TI - [Behavior and pathogenicity of larva of Toxocara canis Werner 1782 (Anisakidae) in the mouse]. AB - To evaluate the interdependence between pathological changes and the level of infection the behaviour of Toxocara canis larvae in the host, the course of the disease as well as quality and quantity of histological changes were investigated after experimental infection with 1,000, 500, 250, and 125 larvae respectively. The main places where the larvae of Toxocara canis were found at any time after infection were musculature and brain. Regardless of the level of infection the absolute and relative number of larvae in the brain increased linearly, and parallel decreased in musculature. After the 60th day post infection the mice infected with 1,000 larvae showed compulsive movements, disturbance of equilibrium and paralysis of the hindlegs. The mice infected with 500 larvae showed similar symptoms 30 to 40 days later. Mice with weaker infections only showed slight disturbances of the general condition at the end of the trials. In the brain of all animals infected with larvae of Toxocara canis inflammatory reactions were found. Severe destructive changes in the nervous substance together with clinical symptoms were seen only in higher infected mice. PMID- 2596203 TI - [The parameters of the molecular evolution of the 11S globulins of plants]. AB - Nucleotide sequences of cloned cDNA coding for soybean storage protein glycinin and deduced amino acid sequences of basic polypeptides (subfamily II) of glycinin are compared with the amino acid sequences of 11S globulins from other plants. An average number of amino acid substitutions in various evolutionary branches is calculated. A proportional dependence is established between the average number of substitutions per site (the evolutionary distance) and the hypothetical term of divergence of corresponding taxa. The evolution rate of 11S globulins and a term of divergence of the two subfamilies of 11S globulin polypeptides in Fabaceae is estimated. PMID- 2596204 TI - [The intensity of oxidative phosphorylation and the function of the adenylate system in the liver mitochondria of active and hibernating susliks Citellus undulatus]. AB - The state of adenylate system and intensity of oxidative phosphorylation in liver mitochondria of active and hibernating ground squirrels were studied depending on the concentration of extramitochondrial Ca2+ ([Ca2+]ex). It was shown that at [Ca2+]ex.10(-7) M, the content of ATP as well as ATP/ADP ratio are slightly lower in the mitochondria of hibernating ground squirrels than in the mitochondria of active animals. The other parameters of the adenylate system under the same conditions differ insignificantly. [Ca2+]ex increase to 10(-6) M has little effect on the parameters of the adenylate system of active animals. On the contrary, the mitochondria of hibernating ground squirrels are strongly affected: the level of ATP is 1.5-fold and the ratio of ATP/ADP is almost 2-fold decreased. At both [Ca2+]ex the intensity of oxidative phosphorylation is essentially higher in the mitochondria of active ground squirrels. With increasing [Ca2+]ex the rate of ATP synthesis decreases, and in the mitochondria of hibernating animals the decrease is more pronounced than in the mitochondria of active animals. Thus, oxidative phosphorylation and adenylate system of mitochondria from hibernating ground squirrels are more sensitive to [Ca2+]ex increase than those of the mitochondria of active animals. PMID- 2596205 TI - [The enzyme systems of the cavitary and membrane hydrolysis of foodstuffs in the ontogeny of Karakul sheep]. AB - By means of biochemical determination of the activity of hydrolases in the digestive system, studies have been made on the enzymic spectrum in the pancreas and small intestine in postnatal life of astrakhan sheep. It was shown that to the moment of birth, animals possess the developed mechanisms of the initial and final stages of hydrolysis of proteins and lipids. At this period, carbohydrate hydrolysis system is presented only by lactase, the activity of pancreatic alpha amylase, intestinal gamma-amylase and maltase being very low, whereas the activity of saccharides is absent at all. During further development of sheep, the activity of all digestive hydrolases gradually increases, except that of lactase which is almost absent in adult specimens. Saccharides activity was not find in the mucose of the small intestine within the whole postnatal life. PMID- 2596206 TI - [The action of cisplatin on the developing meso- and metanephros of chick embryos]. AB - Injection of various doses of cisplatin to 2-14-day chick embryos showed that within 2-8 days of incubation cisplatin produces total toxic effect, the number of dead embryos being dependent on a dose of the drug. Within 9-16 days of incubation, i.e. a period when both the mature mesonephros and the developing metanephros are in action, no significant changes were observed in the content of urea and uric acid, the weight of the meso- and metanephros, their water content, and ion content of the blood. Electron microscopic studies revealed no structural changes in the renal tubules. The data obtained suggest that cisplatin does not produce any nephrotoxic effect in chick embryos irrespectively of their age. PMID- 2596208 TI - [The reaction of the N-cholinoreceptors of the isolated neuron of the mollusk Planorbarius corneus to polymethylene-bis-trimethylammonium compounds]. AB - Experiments have been made on isolated giant neurones of the mollusc Planorbarius corneus using clamp technique at temperatures 10 and 20 degrees C. The effect of polymethylene-bis-trimethylammonium compounds with 7-18 methylene groups in the molecule (C7...C18) on N-cholinoreceptors with chloride ionic channels was investigated. All these drugs were found to be agonists. Their cholinomimetic activity depends on the number of methylene groups (up to a certain extent) in their structure. This finding stands true also for skeletal muscles of frog and chick, as it had been shown in our earlier experiments. Analysis of membrane current fluctuations showed that the elementary current, the channel opened time, temperature coefficient (Q10) of the neuronal response to application of an agonist and the calculated Q10 of the reaction rate of the agonist with cholinoreceptor did not significantly differ for C8...C18 from the reaction rate of the agonist with cholinoreceptor. As compared with C8, C12...C18 exhibited 30 ... 40 times higher cholinomimetic activity, all other parameters in them being similar. Presumably, this difference is explained by concentrating capacity of C12...C18 at the membrane site because of their higher hydrophobic properties. PMID- 2596207 TI - [Seasonal changes in the energy metabolism of subarctic rodents]. AB - In widespread species, northern taiga voles, most significant differences in the intensity of energy metabolism (M), maximum (Mmax) and reserve (Mres) metabolism were observed at winter temperatures (-5-20 degrees C): Clethrionomys rutilus greater than C. rufocanus greater than Microtus oeconomus; differences in seasonal increase of Mmax and Mres exhibit an inverse proportion. Seasonal changes in M and Mmax in autochthonous tundra rodents indicate that Lemmus sibiricus belongs to a more eurybiont species as compared to Dicrostonyx torquatus. The main characteristic feature of seasonal adaptation of M in lemmings, as compared to voles, is the evident decrease of M value in winter which is accompanied by a more significant increase of Mmax and Mres. Operative pattern and high seasonal mobility of chemical thermoregulation in lemmings are suggested which account for adaptation of these animals mainly to short-term extreme effects of low temperatures. PMID- 2596209 TI - [Qualitative differences in the reactions of the spinal nerves of the frog Rana temporaria during chemical stimulation of the skin]. AB - Studies have been made on total impulse activity in the skin nerves of the frog during application of acid solutions as well as during tactile stimulation. It was shown that the reactions to various stimuli differ with respect to their pattern and amplitude of integrated response curve which reflects changes in the frequency of total impulsation. In responses to test solutions and tactile stimulation, different units may be involved which specifically react to each of the stimuli. This specificity of single elements is also revealed during changes in the evoked total activity resulting from superficial skin anaesthesia. Possible nature of peripheral structures involved in these reactions is discussed. PMID- 2596210 TI - [Trees of maximum approximation: topologic approach to the task of constructing trees of maximum approximation]. PMID- 2596211 TI - [Positive inotropic action of acetylcholine on the heart ventricles of the chick embryo]. AB - Acetylcholine increased twitch tension in the whole ventricle or in ventricular strips from 2-10-day chick embryos. The effect of acetylcholine was mediated by muscarinic receptors, since it was prevented by atropine, but not by tubocurarine or propranolol. Prostigmine significantly increased the sensitivity to acetylcholine in the strips from 7-day embryos, being almost ineffective in the strips from 3-day embryos. The decrease in acetylcholine sensitivity in the developing chick embryo is presumably associated with the increase in cholinesterase activity of the myocardial tissue. PMID- 2596212 TI - [The spectral characteristics of the electroencephalogram of the toad Bufo bufo L. during the active and passive behavior of the animal in its circadian cycle]. AB - Using implanted electrodes, studies have been made on spectral EEG characteristics in the forebrain and midbrain of the toad during diurnal cycle. It was shown that rest constitutes more than 2/3 of 24-hour period, being presented mainly by passive wakefulness. A form of rest was revealed which may be classified as a sleep-like one. PMID- 2596213 TI - [The effect of estivation and hibernation on conditioned defensive reflexes in the suslik Citellus fulvus]. PMID- 2596214 TI - [The serotonin and dopamine content of helminths in different classes]. AB - Analysis of the presented data shows that in all representatives of cestodes serotonin is present, dopamine being found only in few species. In trematodes, the dominant amine is presented by dopamine, whereas in some trematodes serotonin was also found. Concentration of biogenic amines in other classes of helminths is usually essentially lower than that in cestodes and trematodes. PMID- 2596215 TI - [Biogenic monoamines of the brain and spinal cord pia mater in vertebrates]. AB - Fluorimetric studies have been made on the content of adrenalin, noradrenaline, serotonin, dopamine, and tryptamine in the pial matter of the brain and spinal cord of fishes, birds and mammals including man. Using histochemical method with glyoxylic acid, biogenic monoamines were revealed in the adrenergic nerve fibers and monoaminocytes. Their total content in the pial matter of the brain is approximately the same in all vertebrates, being significantly lower in man. Higher concentration of adrenergic axons and lower amount of monoaminocytes in human subjects reveal the key role of the nervous influences in regulation of hemodynamics of the brain. PMID- 2596216 TI - [In vivo protein synthesis from 14C-substrates in porcine tissues during the transition to postnatal development]. AB - [2-14C] leucine, [1-14C] alanine, [1-14C] glucose, [1-14C] lactate and [1-14C] pyruvate utilization in the protein synthesis has been studied in vivo at early stages of postnatal development of piglets. It has been established, that during the first 24 hours after birth the protein synthesis intensity, judging by [2 14C] leucine incorporation, in liver, skeletal muscle, duodenal wall and subcutaneous tissue of piglets increases 5, 7, 6.5 and 2.1 times respectively. At the age of 1-2 h the radioactive carbon incorporation from [1-14C] glucose into the brain proteins is more pronounced than into the proteins of liver and skeletal muscle. During the first days of life the intensity of the label incorporation from [1-14C] glucose into liver and skeletal muscle proteins of piglets is enhanced, whereas in brain it remains at the same level. The degree of 14C carbon incorporation from [1-14C]-alanine, [1-14C] pyruvate and [1-14C] lactate into the liver and skeletal muscle proteins of 5-days-old piglets is approximately the same, 14C substrates of protein synthesis in brain and subcutaneous adipose tissue having some peculiarities. PMID- 2596217 TI - [The cholinomimetic activity of alkyltrimethylammonium compounds in experiments on the isolated mollusk neuron and on frog and chicken skeletal muscle]. AB - As revealed by contractile reaction of frog and chick muscles and by changes in the membrane current of isolated molluscan neurone, cholinomimetic activity of alkyltrimethylammonium compounds (ATMC) in the highest in drugs with 4 and 5 methylene groups in a molecule. The decrease in the activity with the decrease in the number of methylene groups was more evident in chick muscle; the decrease in the activity due to the increase in the number of these groups was most significant in experiments on molluscan neurone. Analysis of membrane current fluctuations showed that elementary current does not depend, whereas channel open time only slightly depends on the number of methylene groups in ATMC. However, with the increase of the number of methylene groups above 4, gradual decrease was observed in the ability of ATMC to increase at low (threshold) concentrations the membrane current (response) in the neurone. This decrease in the potency of ATMC correlated with the increase in Q10 value for neuronal response and calculated Q10 value for the reaction rate of ATMC with cholinoreceptor. The decrease in the activity of these ATMC is presumably due to a longer duration of complex formation with cholinoreceptor because of the higher energy barrier. ATMC with 8 and 9 methylene groups at high (saturating) concentrations elicited significantly smaller neuronal response with higher Q10 value. It is suggested that this phenomenon is due to a longer duration of complex formation with cholinoreceptor because of a higher energy cost. PMID- 2596219 TI - [The symmetry of the genetic code and the conservative nature of allowed mutations as a factor in evolution]. PMID- 2596218 TI - [Sexual differences in certain forms of motor asymmetry in rats]. AB - Using three tests, studies have been made on locomotor lateralization in Wistar rats. It was shown that rat prefer the left paw for obtaining food from a tube, this preference being more pronounced in females. Females are more asymmetric also in preference of a side turn in a labyrinth: they choose the right side. In males, the preference of the right and left turns, as well as the absence of locomotor asymmetry were almost equal. These data are rather similar to those obtained for human subjects. Studies on the direction of rotation of rats after apomorphine injections did not reveal any sex differences or populational preferences. PMID- 2596221 TI - [The forming of an active avoidance reaction in representative rodents born mature and immature]. PMID- 2596220 TI - [Changes in the neuronal membrane potential of the mollusk Planorbarius corneus under the action of cardiac glycosides]. AB - In experiments on isolated neurones from the gastropod mollusc P. corneus, strophantin and digoxin in low concentrations produce slow hyperpolarization, in higher ones--depolarization; at concentrations about 1 mM, hyperpolarization was more evident. In all cases, the decrease in membrane resistance was observed. Presumably, membrane permeability for potassium ions increases. During application of the drugs in concentrations 10-100 microM, hyperpolarization may be masked by depolarization due to block of Na,K-pump. Higher concentrations, increasing potassium permeability of the membrane, may result in substitution of depolarization by hyperpolarization. PMID- 2596222 TI - [The pathomorphology of hypophyseal adenomas]. AB - The paper presents the results of morphological study of 668 cases of adenomas of the hypophysis on the basis of light optical and electron microscopy techniques, immunohistochemical analysis and a number of other methods. Correlation between cellular, tissue and hormonal characterization of adenomas and their capacity for invasive, infiltrative growth and relapses have been studied. PMID- 2596223 TI - [Experience with transcranial surgery of hypophyseal adenomas]. AB - The article generalizes experience in intracranial operations on 453 patients performed at the Institute of Neurosurgery, AMS, USSR in 1983-1987. The tumors had a pronounced extrasellar growth in most cases. The surgical approaches and the peculiarities of surgical techniques in removal of pituitary adenomas are described. The importance of microsurgical techniques which raise the radical character of the surgical interventions and improve their results is discussed. PMID- 2596224 TI - [Hypophyseal adenomas with invasive growth]. PMID- 2596226 TI - [The status of the problem of treating hypophyseal adenomas]. PMID- 2596225 TI - [Transnasosphenoidal microsurgery of hypophyseal adenomas]. AB - The results of surgical treatment of 550 patients through a transnasosphenoidal approach are analysed. The results of management of endosellar and endoextrasellar adenomas are discussed. Various groups of patients are set apart according to the hormonal activity of the tumor. The indications and contraindications for operations through a transnasosphenoidal approach are specified beforehand. The complications in transnasal operations are described and mortality is analysed. PMID- 2596227 TI - [Current aspects of the diagnosis and combined treatment of closed craniocerebral trauma in the acute period]. PMID- 2596228 TI - [Craniocerebral trauma and stroke]. AB - It was demonstrated from analysis of 685 cases that craniocerebral injury is attended by the development of secondary acute disorders of cerebral circulation in 8.9% of cases. Cerebral apoplexy is encountered in craniocerebral trauma 4-5 times more frequently (in 25% of cases) among patients with arterial hypertension and 2-2.5 times more frequently (in 12% of cases) among those with diabetes mellitus than in patients with a nonacerbated somatic anamnesis (in 5.4% of cases). PMID- 2596229 TI - [Psychotherapy of patients with a history of craniocerebral trauma]. AB - The management of patients in the early period of craniocerebral trauma according to a psychotherapeutic program comprising reasonable psychotherapy, prolonged hypnotic sleep, psychotherapeutic passes, a mental hygiene complex, and a special variant of autogenous training increases essentially the efficacy of treatment of patients and the possibility of their return to work. The bordering neuropsychic disorders and inadequate personal reactions to the disease are deactualized. PMID- 2596230 TI - [The information value of the EEG in the acute period of subarachnoid hemorrhage as a consequence of rupture of intracranial aneurysms]. AB - The article deals with the results of electroencephalographic (EEG) examination of 65 patients in the acute period of subarachnoid hemorrhage of nontraumatic genesis. The revealed changes in the electrical activity of the brain are compared with the level of disturbed consciousness, the severity of the clinical condition, and the presence of complicated or noncomplicated form of subarachnoid hemorrhage. The main factors determining the degree of disorders of the EEG pattern are discussed. It is shown that the EEG data possess high prognostic significance in determining the outcome of operative treatment of patients in the acute period of the disease. PMID- 2596231 TI - [Dermoid cysts of the orbit spreading into the cranial cavity]. AB - Operations were performed through a transcranial approach on 12 patients with dermoid cysts of the orbit spreading into the cranial cavity. All patient had a defect in the orbital roof which extended to the lateral wall in 8 patients. The capsule of the cyst was connected with the dura mater and the orbital periosteum with adhesions. With the use of an operative microscope or operative magnifying glass and microsurgical instruments the dermoid cysts were removed without injuring the dura mater and orbital periosteum and good functional and cosmetic results were produced. PMID- 2596232 TI - [The early diagnosis of acoustic neurinomas]. AB - The work analyses the results of complex examination (by an otoneurologist and neuroroentgenologist) of 34 patients with neurinoma of the 8th cranial nerve measuring from 13 to 25 mm. It is difficult to establish the diagnosis of neurinoma of the 8th nerve in the early stage; its recognition is based on the combination of otoneurological findings and the results of computed tomography, particularly computed cisternography with Amipaque. Despite the small size of the tumor, all patients had local symptomatology in the form of unilateral neurosensory deficiency or deficiency of hearing, vestibular excitability, and taste (on the anterior two thirds of the tongue). Three variants of tumor localization were distinguished by computed tomography: inside the canal, lateral, and medial. Computed cisternography with Amipaque yielded additional information on the size of the tumors and showed more exactly their relation to the brain stem. The results of computed tomography and cisternography corresponded completely to the otoneurological data which reflected the degree of the tumors' effect on the brain stem structures adequately and subtly. PMID- 2596233 TI - [Diagnosis and microsurgical treatment of syringomyelia]. AB - The results of examination (96) and microsurgical operations in 39 patients with syringomyelia are discussed. The average age and duration of the disease before the operation were, respectively, 36 and 11 years. Radiological and electrophysiological methods were used in establishing the diagnosis. Operative treatment included restoration of c.s.f. circulation at the level of the craniovertebral junction in 12 and ultrasonic myelotomy in the entry zone of the posterior radices in 27 patients. The results were positive in most patients with a catamnesis of 6-27 months, mainly when the disease was of a short duration. PMID- 2596235 TI - [Venous malformation of the cranial vault (sinus pericranii)]. PMID- 2596234 TI - [An intracerebral cystic cavernous angioma]. PMID- 2596237 TI - Diagnosis and treatment of inflammatory intestinovesical fistulas. AB - The histories of 3 patients operated for inflammatory intestinovesical fistulas are reviewed. Two of them were treated for colovesical, one for ileovesical fistula. The questions concerning the development, diagnostics and surgical management are discussed in detail. The importance of cystoscopy in diagnosis is emphasized. In all three patients one-session operations were performed with good results. PMID- 2596236 TI - [Topographo-anatomic classification of hypophyseal adenomas]. PMID- 2596238 TI - Use of CO2 laser knife in gastroenterological surgery. AB - Favourable results obtained by using the RT TLS61 CO2 laser of TUNGS-RAM, of a performance of 60 W are reported. It is emphasized that the device has several advantages in surgical gastroenterology over the traditional cutting instruments. The light of the device coagulates the smaller than 0.5 mm vessels during cutting. On opening the gastrointestinal tract-contrary to electrocautery-the necrotic zone is narrower, which may be of importance from the point of view of suture insufficiency. The device provides more favourable conditions for ablastic operations than do the traditional cutting instruments. PMID- 2596239 TI - Cytochemical detection of nickel in endometrial carcinoma during progestogen treatment. AB - During progestogen treatment, nickel ions were detected in the human endometrial tissue of patients with endometrial carcinoma by the dimethyloxime cytochemical method. In this paper, the mechanism of action of nickel is dealt with and, because nickel ions have earlier not be detected in human endometrial carcinomatous tissues, the question arises as a result of what kind of cell biological processes, nickel ions appear in the cells of endometrial carcinoma. It is still to be answered whether the progestogen treatment applied can be correlated with the appearance of the trace element in the carcinomatous cell. PMID- 2596240 TI - The use of nonspecific esterase in assessing the effectivity of cryotherapy on the uterine cervix. AB - Cryotherapy of the uterine cervix can produce tissue damage of various depths. It is very important to be familiar with the extent of tissue damage in standardizing the treatment and assessing its effect. In the present work nonspecific esterase reaction was applied for the early study of tissue damage. It was found that this method can be used with benefit in the early assessment of the effect of freezing. The enzyme reaction was primarily a sensible marker of cell damage in the cervical cells. PMID- 2596241 TI - Ultrastructural alterations in the ectocervical epithelium after cryotherapy. AB - The central problem of the cryosurgery of the uterine cervix in gynaecological practice is the extension in depth of the tissue impairment. The ultrastructural alterations were studied in the surgical material of portioplasties performed two hours after cryotherapy of the non-malignant ectocervical changes of fertile women. For control, the unfrozen regions of the same cervix were used. The vacuolization of the cytoplasm and partial fragmentation of the mitochondria appear to be detectable and reversible changes. Parallelly, severe irreversible nuclear impairments can be demonstrated in the basal and parabasal layers of the cervical epithelium. The relative connective tissue insensitivity, in contrast to the damage of the epithelium, verifies the advantage of cryosurgery in the therapeutic applicability. PMID- 2596242 TI - Endoscopic removal of residual calculi from horse-shoe kidney and ureter. AB - Ureteroscope and pyeloscope were used for removing residual calculi following open operation of horseshoe kidney. Endoscopic nephrolithotomy is suitable for preventing complications of open operations. PMID- 2596243 TI - The effectiveness of venous hypothermia in the left kidney. AB - Twenty renal parenchyma operations of the left kidney were performed in venous hypothermia. The hypothermic solution was perfused via the spermatic (ovarian) vein, outflow occurred through the vessels opened by the incision. The effectiveness of venous hypothermia was measured by the probe of an electrical thermometre inserted into the renal tissue. The temperature of the cooled kidney became constant between 20 and 23 degrees C by using a perfusion solution of 4-5 degrees C. The method can be used for its simplicity and safety also in extensive renal parenchyma operations, its only limitation is that it can be performed only on the left kidney. PMID- 2596244 TI - Pacemaker twiddler's syndrome (rotation of the pacemaker around the electrode cable, a rare complication of pacemaker therapy). AB - Rotation of the pacemaker generator around the electrode cable (i.e. twiddler's syndrome) was observed by the authors in six cases during the implantation of 4250 pacemakers. Twiddler's syndrome developed in three cases following implantation and in three cases after the replacement of the pacemaker. As a result of the rotation of the device, displacement of the electrode occurred in all cases. The factors predisposing to rotation of the device were as follows: (i) a loose, dilated pocket in 5 cases; (ii) seroma formation around the device in 2 cases; (iii) manipulation with the pacemaker in one case. For treating twiddler's syndrome, reimplantation was performed, fashioning a small and tight pocket for the device and fixing it by transfixing sutures. After reimplantation, the patients became complaint free, no recurrences occurred. PMID- 2596245 TI - Effects of the beta-2 receptor agonist terbutaline on hemodynamics and gas exchange in endotoxin shock. AB - The effects of the beta-2 receptor agonist, terbutaline, on hemodynamics and gas exchange were evaluated in sheep exposed to endotoxin shock. Terbutaline was not given until signs of shock and lung injury had developed. Twenty sheep were anesthetized and ventilated without PEEP. After 90 min of stabilization (t = 0) all animals received E. coli endotoxin 10 micrograms/kg by i.v. infusion during 15 min. Thirty minutes later (t = 30) 10 animals (group TER) received i.v. infusion of terbutaline, 20 micrograms/kg/h, during 4 hours, while the other 10 served as controls (group S). The endotoxin infusion resulted in marked increase in pulmonary artery pressure (PAP) and a significant decrease in mean arterial pressure (MAP), respiratory compliance, arterial oxygen tension (PaO2) and oxygen delivery index (DO2) in both groups (t = 15 and t = 30). After 4 hours the PAP had decreased significantly in the terbutaline treated animals, but remained high in the controls (p less than 0.01). Also, MAP, PaO2, DO2 and compliance improved significantly in the terbutaline treated animals. The wet to dry weight ratio of the lungs was 4.85 +/- 0.2 in the terbutaline treated and 5.35 +/- 0.5 in the controls (p less than 0.05). It was concluded that terbutaline treatment improves gas-exchange and hemodynamics in sheep exposed to endotoxin shock. PMID- 2596246 TI - High plasma levels of extrinsic pathway inhibitor and low levels of other coagulation inhibitors in advanced cancer. AB - Serial determinations of plasma coagulation inhibitor levels were performed with chromogenic substrate activity assays in 7 patients with cancer. At time of diagnosis normal median activities of Antithrombin, Protein C, Heparin Cofactor II and Extrinsic Pathway Inhibitor were found. The inhibitor activities changed significantly with the progress of malignant disease; Antithrombin, Protein C and Heparin Cofactor II decreased whereas Extrinsic Pathway Inhibitor increased. Determinations in 13 additional patients in the terminal phase of cancer confirmed this finding. The inhibitor activities were expressed in per cent of a pooled reference plasma. In the total series of 20 patients studied, median activity of Extrinsic Pathway Inhibitor was 183% (range 61-378%) and significantly (p less than 0.005) above age-adjusted normal reference 10 days (range 1-20 days) prior to death. Median activities of Antithrombin was 59% (range 20-109%), of Protein C 54% (range 24-130%) and Heparin Cofactor II 59% (range 33-110%), all significantly below age adjusted normal reference (p less than 0.001). The coagulation inhibitor levels seem related to the stage of disease in patients with cancer. PMID- 2596247 TI - Long-term follow-up after endoscopic management of retained and recurrent common duct stones. AB - Endoscopic sphincterotomy (EST) was attempted on 128 patients because of retained or recurrent common bile duct stones. The duct was cleared in 118 cases (92%). Early complications arose after 27 (16.5%) of 164 sphincterotomies, with haemorrhage most common. Emergency laparotomy was performed in four cases. There were four deaths within a month of EST, two of them directly attributable to EST. In seven of the 118 patients with successful EST late complications (stenosis and/or recurrent stone) appeared during a median follow-up of 57 (range 24-101) months (after less than 2 years in 6 cases). Restenosis and new stones could usually be endoscopically treated. Ascending cholangitis was not a problem, provided that the bile flow was unobstructed. EST is relatively safe, and must now be considered the procedure of choice for postcholecystectomy choledocholithiasis especially in elderly or high-risk patients. EST in young, fit patients is more controversial, and requires further detailed longitudinal analyses. PMID- 2596248 TI - Jejunoileal bypass for morbid obesity. Report of a series with long-term results. AB - Of 72 patients who underwent jejunoileal bypass because of morbid obesity, 69 could be evaluated with special reference to long-term (median 11 years) results. One of the other three had fatal anastomotic leakage, one underwent resection and reversal of shunt because of postoperative gangrene in the bypassed segment, and one died of sepsis and liver failure following cholecystectomy 6 months after bypass. The median body mass index (kg/m2) fell from 45.4 preoperatively to 33.2 after 16 years. Shunt-related complications in early and late follow-up were diarrhoea (n = 15), anal/perianal disorders (15), arthralgia (15), urinary calculi (16), cholelithiasis (5), severe flatulence (7), liver cirrhosis (5), intestinal tuberculosis (1), ileitis (1), severe electrolyte disturbance (4), hypomagnesaemia (22), hypokalaemia (8), and deficiency of vitamin B12 (24), iron (24) and folate (17). Although jejunal bypass effectively reduces weight, the patients are at continuous risk of many complications. However, the improvement in quality of life should not be underestimated. PMID- 2596249 TI - Changes in the connective tissue composition of the submucosal layer of colonic anastomosis. An immunohistologic study in rats. AB - Submucosal healing of colonic anastomosis was studied in rats. The unprepared sigmoid colon was divided and colo-colostomy performed, using a one-layer inverting technique. Frozen sections were studied immunohistologically with specific antibodies to fibronectin, laminin and collagen types I, III, IV and V. From the first to the fifth postoperative day the submucosa was highly oedematous. A clear fibronectin reaction was observed in the submucosa, reaching maximum on postoperative day 5. From day 3 onwards the fluorescence intensities of types I and III collagen in the young granulation tissue and of types IV and V collagen and laminin in the regenerating capillaries rapidly increased, with maximum on day 7. The striking changes in the submucosa indicate that the healing process involves not only the actual area of the anastomosis, but also widely the submucosal layer of the adjacent intestine. PMID- 2596250 TI - Choledochoduodenal fistula: a rare complication of duodenal ulcer. Case report. AB - In a 29-year-old man with pyloric obstruction, plain abdominal radiography showed gas in the biliary tree. Gastroscopy revealed severe duodenal stenosis with a large posterior ulcer, and barium from a test meal passed into the common bile duct. Ten days after truncal vagotomy and gastrojejunostomy, signs of ascending cholangitis appeared. Following antibiotic treatment and cholecystectomy the patient recovered. PMID- 2596251 TI - Successful fibrin seal closure of a contaminated fistula. Case report. AB - In a 43-year-old woman, a large, contaminated fistula, initially with vesicointestinal communication, was successfully closed by application of fibrin seal. The course of three sealing attempts indicated that local pretreatment with antibiotics may have been important for the final result. At 4-year follow-up examination there was no recurrence of the fistula. PMID- 2596252 TI - Bilateral phrenic nerve palsy associated with benign thyroid goiter. AB - Phrenic nerve palsy secondary to benign thyroid enlargement is a previously unreported complication. Large goiters, particularly substernal, may impinge upon adjacent structures, often leading to significant symptoms such as dysphagia or dyspnea due to airway compression. The phrenic nerve may be stretched by a large goiter along its course in the neck, but the more likely site of injury is the point at which it enters the thoracic cavity adjacent to the first rib. Such an injury, caused by compression, may go unrecognized if unilateral, as symptoms would be uncommon. However, bilateral phrenic nerve palsy can cause significant dyspnea due to pulmonary insufficiency, particularly in an elderly patient with cardio-pulmonary disease. Early operative treatment of the goiter may prevent this complication or limit its severity, thus avoiding permanent nerve injury. PMID- 2596253 TI - The effect of hyperosmolar infusions on survival after hemorrhage. AB - Hyperglycemia has previously been reported beneficial for survival after hemorrhage. In the present investigation, rats depleted of liver glycogen after 24 h food deprivation were infused either A: isotonic NaCl (300 mosm/kg H2O), B: glucose (1,800 mosm/kg), C: Xylose (2,000 mosm/kg) or D: NaCl (1,800 mosm/kg), during 60 min hemorrhage, and observed for recovery or death for seven days. During hemorrhage, all animals given hyperosmolar infusions had higher serum osmolality and greater plasma refill compared to group A. Increments in serum osmolality correlated inversely to hematocrit developments, p less than 0.05. Only 2/18 animals given isotonic NaCl survived, while survival in the other groups were 14/18 (glucose infused), 20/22 (xylose infused) and 20/20 (hypertonic NaCl). Best survival was noted in the groups with the highest final osmolality, and largest reduction in hematocrits; groups C and D, while significantly more animals given glucose died compared to group D. It is concluded that induction of hyperosmolality during the early phase of hemorrhage is associated with increased survival in hemorrhage, irrespective of hyperosmolar agent infused. The benefits of hyperglycemic hyperosmolality is primarily related to the osmolar properties of this solute, and not the immediate need for glucose as substrate. PMID- 2596254 TI - The perioperative changes in glomerular filtration and renal blood flow in patients with obstructive jaundice. AB - Experimental alterations in renal haemodynamics have been observed in obstructive jaundice and these may be the pathophysiological mechanism of increased renal susceptibility to injury in obstructive jaundice. Dynamic 99mTc-DTPA renal scintigraphy was done before and eight weeks after elective hepatobiliary surgery in six patients with obstructive jaundice (bilirubin greater than 100 mumol/l) and in six non-jaundiced control patients to assess changes in glomerular filtration and renal blood flow. Glomerular filtration was lower preoperatively in the jaundiced patients than in the control patients. Glomerular filtration increased postoperatively in jaundiced patients, but decreased in control patients. Renal blood flow was reduced postoperatively in control patients, but not in jaundiced patients. The changes in renal blood flow were different for each group of patients. These results provide clinical evidence of altered renal haemodynamics and a reversible impairment of glomerular filtration in obstructive jaundice. The changes seen in renal blood flow may be the underlying mechanism of increased renal susceptibility to injury. PMID- 2596255 TI - Gastric emptying in adults treated for infantile hypertrophic pyloric stenosis. AB - The gastric emptying rate was scintigraphically determined in 6 women and 26 men who had undergone medical or surgical treatment for infantile hypertrophic pyloric stenosis a median of 29 years previously. Dyspeptic complaints were reported by four of the seven medically treated and nine of the 25 surgically treated group. No intergroup difference was demonstrated in the gastric emptying rate of liquid or solid food, and neither group differed significantly from the normal values. The gastric emptying rate, measured as in this study, thus was uninfluenced by treatment. PMID- 2596256 TI - Solitary caecal diverticulitis. Recognition and management. AB - Nine cases of solitary caecal diverticulitis treated in Kuwait are presented and the literature is reviewed. The preoperative diagnosis was acute appendicitis in all cases, but diverticulitis was detected during surgical exploration and histologically confirmed. The surgical management in seven cases was simple excision of the diverticulum with closure of resultant defect or invagination of the mucosal bulge with suture of the colonic wall. Right hemicolectomy was performed in two cases because of gangrenous patches in the caecal wall and suspicion of carcinoma. Recognition of solitary caecal diverticulitis requires considerable experience, especially in order to avoid more radical procedures such as right hemicolectomy. Solitary caecal diverticulum does not seem to occur in the indigenous people of Kuwait. All nine patients were of other nationalities, including five from countries of the Far East. PMID- 2596257 TI - 99m-technetium-HmPAO-labelled leucocytes in the diagnosis of acute colonic diverticulitis. AB - Eighteen patients with abdominal symptoms clinically resembling acute colonic diverticulitis were studied with 99mTc-labelled leucocytes on average 5 days after the onset of symptoms. The diagnosis of diverticular disease was confirmed in all cases by means of barium enema or sigmoidoscopy. The leucocyte scan was positive in 13 patients, nonspecific in four and unclear in one patient. The diagnostic possibilities in acute colonic diverticulitis are discussed. PMID- 2596258 TI - Torsion of intra-abdominal testicle. Case report. AB - A 19-year-old youth with known right cryptorchidism had repeated attacks of acute abdominal symptoms, previously transient but now intensifying. Surgical exploration revealed a gangrenous intra-abdominal testis, which was successfully removed. Histologic examination confirmed the diagnosis of torsion. PMID- 2596259 TI - Acute necrotizing pancreatitis complicating surgery for renovascular hypertension. Case report. AB - Acute necrotizing pancreatitis is a rare complication of various types of surgery, with a few cases reported after aortic operations. Following renovascular surgery, severe acute pancreatitis developed in three (0.9%) of 332 patients, and was fatal in one case. Various etiologic possibilities are discussed. PMID- 2596260 TI - Ruptured atherosclerotic aneurysm of the superficial femoral artery. Case report. AB - Aneurysms of the superficial femoral artery are rare. A case of multiple superficial femoral artery aneurysms, of which one ruptured, is described. After surgical treatment the prognosis is favourable, but without therapy the risks of rupture, thrombosis or embolization are great. PMID- 2596261 TI - [Morphological analysis of resumption of meiosis observed in oocytes of mouse vesicular follicles]. AB - Resumption of meiosis observed in vesicular follicles of immature 32-34 day-old mice was classified morphologically, and the morphological mechanism to induce resumption of meiosis was examined. Resumption of meiosis was observed in 22.1% of vesicular follicles, and the dominant stage of the meiotic division was the first or second metaphase. Cumulus-enclosed and cumulus-free oocytes were separated from ovaries by dissection of ovaries. All of the cumulus-enclosed oocytes contained germinal vesicle, however 57.9% of cumulus-free oocytes did not, suggesting that the disappearance of cumulus cells around oocytes precedes the induction of resumption of meiosis. About 80-90% of the oocytes with germinal vesicle formed first polar body after 15 hrs of incubation. After incubation of oocytes showing resumption of meiosis, but without the first polar body, 36% of the oocytes extruded the first polar body indicating that resumption of meiosis is associated with progression to the second metaphase. Morphological characteristics of the surrounding structures of oocytes showing resumption of meiosis was classified into three categories; extensive proliferation of granulosa cells, degeneration of cumulus cells and their disappearance around oocytes, and detachment of cumulus cell-oocyte complexes from granulosa cell layer. It was suggested that cell-to-cell interaction among cumulus cells, oocytes and granulosa cells was impaired at the time of resumption of meiosis. Granulosa cells secrete an inhibitor of the resumption of meiosis. The resumption of meiosis after the surge of luteinizing hormone follows cumulus dispersion which make oocytes independent from the influence of granulosa cells by the disruption of communication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596262 TI - Ferritin immunohistochemistry as a marker for microglia. AB - An immunohistochemical analysis of formalin-fixed, paraffin-embedded brain sections was performed with antisera against holoferritin and the light(L) subunit of ferritin. Sections immunostained using anti-glial fibrillary acidic protein (GFAP), Ricinus communis agglutinin-1 (RCA-1) stain for microglia and iron stain (Berlin blue stain) were compared. The L-subunit of ferritin was purified from normal human spleen according to the modified scrapie-associated fibrils purification, and the anti-serum was raised in a rabbit. Both ferritin antisera positively stained resting and, more markedly, reactive microglia, both of which were also stained with RCA-1 but not with GFAP. Ferritin-positive resting microglia were seen more abundantly in cerebral and cerebellar cortices than in white matter. The advantages of ferritin antisera over RCA-1 are as follows. (1) RCA-1 heavily stains blood vessels, while anti-ferritin does not, hence the microglial cells are more readily visualized with ferritin immunohistochemistry. (2) Reactive microglia and macrophages are more strongly stained with anti-ferritin. (3) The staining intensity of ferritin is independent of the length of tissue fixation in formalin. However, anti-ferritin is inferior to RCA-1 in staining resting microglia with a scanty cytoplasm, especially in the white matter, probably because the former recognizes cytoplasmic components, while the latter recognizes cell membrane. Iron stain only gave a reaction to microglial cells in brains with neurosyphilis and to hemosiderin-laden macrophages. Thus, in addition to RCA-1, ferritin antisera are useful as a microglia marker in formalin-fixed, paraffin-embedded sections. PMID- 2596263 TI - Distribution and immunoreactivity of cerebral micro-hamartomas in bilateral acoustic neurofibromatosis (neurofibromatosis 2). AB - Bilateral acoustic neurofibromatosis (neurofibromatosis 2, NF2) accounts for less than 10% of all cases of neurofibromatosis and manifests itself with bilateral acoustic schwannomas, multiple schwannomas of spinal nerve roots, meningiomas, glial tumors and hamartomatous CNS lesions. We have observed dysplastic foci of immature neuroectodermal cells in the cerebral cortex and basal ganglia of six patients afflicted with neurofibromatosis 2, ranging from occasional clusters of immature, dysplastic cells to numerous, confluent lesions. These cells, although often polymorphic and multinuclear did not show mitotic activity or a tendency for neoplastic transformation. To determine the histogenesis of these foci, extensive immunocytochemical reactions were carried out with antibodies to a variety of glial, neuronal and non-neural cell lineages. With the exception of S 100 protein, no immunoreactivity was detectable. S-100 was consistently expressed in these foci, irrespective of their size, location, and degree of polymorphism. On the basis of cytological appearance, distribution and immunoreactivity we tentatively designate these foci as glial micro-hamartomas. Although we did not systematically analyze the CNS of patients with von Recklinghausen neurofibromatosis (neurofibromatosis 1, NF1), the present study strongly suggests that these micro-hamartomas constitute a morphological hallmark of bilateral acoustic neurofibromatosis (NF2). PMID- 2596264 TI - Distribution of lead in the cerebellum of suckling rats following low and high dose lead exposure. A micro-PIXE analysis. AB - The distribution of lead in the cerebellum of suckling Sprague-Dawley rats was examined using a nuclear microprobe for elemental mapping of tissue sections (particle-induced X-ray emission, 3-microns beam of 2.5 MeV protons; micro-PIXE). The rats were injected intraperitoneally with a lead-containing vehicle or vehicle only from ages 1 to 14 days. The calculated doses were 7.8 (low-dose) and 15.6 (high-dose) micrograms lead/g body weight. The rats were killed at 20 days of age. The vascular system was rinsed quickly with 0.15 M ammonium acetate to obtain determinations of intra-parenchymal lead with minimal influence of lead bound to erythrocytes and plasma proteins. Brains were frozen in propane/propylene in liquid nitrogen. Cryostat sections, 15 microns thick, were air dried on formvar coats that covered a hole, 15 mm in diameter, in a plastic disc, and were used for lead analysis by micro-PIXE. Very low concentrations of lead were found in the brain of controls. Lead levels in homogenates from cerebrum and cerebellum measured by atomic absorption spectrometry (AAS) were: low-dose 1.2-2.2 micrograms/g wet weight and high-dose 1.4-2.4 micrograms/g wet weight. The lead levels measured with the micro-PIXE method were in good agreement with the levels found with AAS. Lead was present in the cerebellar white matter in two to three times higher amounts than in the cortical grey (low dose white matter 11-18 micrograms/g dry weight, grey matter 2.0-5.5 micrograms/g dry weight). This was true for both low and high dose exposed rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596265 TI - Ultrastructural changes in skeletal muscle in ovine muscular dystrophy. AB - The initial ultrastructural changes in skeletal myofibers in ovine muscular dystrophy (MD) consisted of focal degeneration of myofibrils and the formation of Z-disc abnormalities, including nemaline rods, in adjacent sarcomeres. Peripheral and central sarcoplasmic masses, which occurred initially in large diameter fibers, contained a mixture of normal organelles and abnormal tubular and fibrillar formations. Vesiculate sarcolemmal nuclei with prominent nucleoli accumulated in central and subsarcolemmal locations in small clusters and short rows. Deformed individual nuclei were sometimes present within nuclear rows. Loss of the myofibrillar mass, increased density of small spherical nuclei, collections of fibrillar and tubular arrays, excessive folding of the sarcolemma and greatly reduced fiber diameter were seen in the end stage of the dystrophic process. Resting satellite cells were present at all stages of lesion development. The morphological progression of the lesions suggested an inherited inability to effectively replace lost myofibrils with ultimate exhaustion of the capacity for repair followed by pathological fiber atrophy. PMID- 2596266 TI - Lectin histochemistry of human gliomas. AB - Formalin-fixed and paraffin-embedded specimens of 24 human gliomas were examined histochemically with five lectins; concanavalin A (Con A), wheat germ agglutinin (WGA), Ricinus communis agglutinin 1 (RCA-1), peanut agglutinin (PNA), and Ulex europaeus agglutinin 1 (UEA-1). Although the staining intensity with lectins was variable, tumor cells in five astrocytomas, three oligodendrogliomas, six ependymomas, and one gliosarcoma, were generally positive for Con A, WGA, and RCA 1, and negative for PNA and UEA-1, whereas those in nine glioblastomas were usually positive for Con A and WGA and negative for RCA-1 and PNA as well as UEA 1. The malignancy in neoplastic astrocytes was correlated with the decrease in binding with lectins, especially RCA-1. Blood vessels, particularly the endothelial layers, in all gliomas were stained intensely with all lectins used. Macrophages showed two staining features with lectins; stippled and granular. The former macrophages were positive for Con A, WGA, RCA-1, and PNA, and negative for UEA-1, whereas the latter macrophages were positive for all lectins used. Thus, the staining characteristics with lectins of macrophages were different from those of any glioma cells and very useful for identification of macrophages in gliomas. PMID- 2596267 TI - Attenuation of soman-induced lesions of skeletal muscle by acetylcholinesterase reactivating and non-reactivating antidotes. AB - It has been reported recently that some oximes reactivating acetylcholinesterase (AChE) exhibit concomitant ganglion-blocking effects which presumably could contribute independently to their powerful antidotal action in organophosphate inhibitor (OPI) poisoning, thus mimicking some unrelated substances which are effective antidotes without reactivating AChE. This raises the question whether OPI-induced muscle lesions, like some other symptoms could also be attenuated by oximes and other antidotes in the absence of AChE reactivation. To test this possibility, the oxime HI-6 was applied at increasing time intervals after the injection of soman until and beyond the point when soman-AChE complex becomes completely "aged" and not capable of reactivation. As the examples of OPI antidotes which do not reactivate AChE, the muscarinic antagonist atropine and the ganglion-blocking agent hexamethonium were also tested on possible attenuation of muscle lesions. The proportions of fibers with lesions, AChE inhibition and muscle fasciculations in experimental groups relative to the controls treated with soman only were evaluated. The results show that HI-6 can attenuate lesions only if AChE is partially reactivated and muscle fasciculations are permanently eliminated. However, atropine does not affect either AChE inhibition or muscle fasciculations and is also ineffective in counteracting the lesions in spite of its potency as an effective general antidote. Hexamethonium also does not affect AChE inhibition, but abolishes fasciculations and effectively attenuates muscle lesions. The latter findings reveal the existence of lesion-protecting mechanisms unrelated to AChE reactivation, which if further elucidated might become potentially relevant for additional treatment in OPI poisoning. PMID- 2596268 TI - Neuronal counts from four cortical regions of alcoholic brains. AB - Neuronal loss from the frontal superior cortex of the brains of alcoholics has recently been documented. In addition to this, a reduction in the mean neuronal area was also seen in the frontal and motor cortices. This suggested a regional specificity of neuronal damage in the brains of alcoholics. Further quantitation of other cortical regions of the same cases as used in the above study has been performed. The frontal cingulate and temporal cortices were examined and there was found to be no significant alteration in the number of neurons when compared to a control population. There was, however, a significant reduction in the mean size of the neuronal soma in the frontal cingulate cortex (P less than 0.05). These data support the hypothesis of regional variations in the severity of cerebral cortical damage in alcoholism with shrinkage of neurons in most regions examined but neuronal loss only in the superior frontal gyrus. PMID- 2596269 TI - Medulloblastoma. An immunohistological study of 50 cases. AB - Fifty paraffin-embedded medulloblastomas (31 in children and 19 in adults) were reacted with a panel of ten antibodies to glial, neuronal, mesodermal and epithelial antigens. The tumours were divided according to their histological features into three groups: classic, desmoplastic and highly vascular. Reactivity for glial fibrillary acidic protein was observed in 20 cases. Forty tumours reacted with PGP9.5 (neuronal marker) in clusters of poorly differentiated cells, cell cords and some scattered cells. Cells forming rosettes were mostly negative except for slight central reactivity. Eight of the 40 tumours contained neurofilaments. In scattered cells somatic reactivity for vimentin was found in 14 tumours. Ten cases showed positivity for S-100 with a nuclear and perinuclear pattern. No difference in reactivity in relation with age was observed. Desmoplastic medulloblastomas showed less reactivity for glial and neural markers. It was concluded that medulloblastoma shows degrees of differentiation as evidenced by the expression of various proteins. Differentiation occurs along two lines: glial and/or neuronal. Most tumours also contain a component of poorly differentiated cells which may differentiate into one of these two lines or act as primarily stem cells. PMID- 2596272 TI - Selected trace elements and proteins in serum of apparently healthy newborn infants of mothers who smoked during pregnancy. AB - The serum concentrations of selected trace elements and proteins in cord blood from 17 newborn infants whose mothers were habitual smokers were compared with values from 22 infants of non-smoking mothers. All the mothers were healthy with normal pregnancies and deliveries. Cigarette smoke exposure was verified by determinations of nicotine, cotinine and thiocyanate concentrations in cord blood. Infants of smoking mothers had a slightly lower mean birth weight (3490 +/ 430 g) than control infants (3780 +/- 460 g). Infants of smokers had lower serum iron (p = 0.05) and prealbumin (p less than 0.05), but higher serum copper (p less than 0.05) and ceruloplasmin (p less than 0.01) levels than the controls. Infants of smoking mothers tended to have higher levels of the acute-phase reactants alpha-2-macroglobulin and orosomucoid, but lower levels of albumin, transferrin and retinol-binding-protein, although differences were not statistically significant. PMID- 2596270 TI - Immunohistological investigation of mononuclear cell infiltrates in meningiomas. AB - Immunohistochemical analysis of inflammatory cell density and infiltrate subpopulations in 42 meningiomas was performed. Evaluation of infiltrating cell density was carried out by cell counting. Meningothelial and fibroblastic meningiomas contained an average of 3% mononuclear cells; the few lymphocytes were localized in the perivascular spaces. In subtypes with cellular atypies and recurrent tumors, the inflammatory cells increased up to 9%. We found small mononuclear cell clusters in the tumor parenchyma in addition to the perivascular infiltrates. Marked degrees of infiltration were found in anaplastic meningiomas (average 13.5% of total cells). The lymphocytic infiltrates were localized in multilayered perivascular cuffings and intraparenchymal cell clusters. The composition of the infiltrates, i.e., predominantly a mixed staining of cytotoxic/suppressor and helper cell phenotypes, did not vary in the different subtypes. We conclude: (1) that inflammatory infiltration is more frequent and denser in malignant than in benign meningiomas; and (2) that the tumor defense mechanisms in meningiomas are mediated particularly by T cell mediated immunity. PMID- 2596271 TI - Melanotic ganglioglioma of the pineal region. AB - A melanotic ganglioglioma was biopsied in the pineal region of a 12-month-old girl who preoperatively underwent a ventriculo-peritoneal shunt for hydrocephalus and postoperatively received radiotherapy. The tumor was subtotally excised when the girl was 7 years and 4 months of age. Histologically, it demonstrated mature neurons in disorganized clusters and in well-differentiated cerebrum-like tissue, rare binucleated neurons, glia similar to normal gray matter, and bands of fibrous tissue containing heavily pigmented cells. Ultrastructurally, melanosomes of stages I to IV were identified in the pigmented cells. An origin involving retinal differentiation of the primitive pineal gland was not supported; the tumor was negative for both retinal S-antigen (MAbA9-C6) and cellular retinal binding protein (CRALBP). This report demonstrates the ability of a cerebral neoplasm to contain neurons, glia, and melanin-containing cells; all of which are neuroectodermally derived. PMID- 2596273 TI - Metabolic differences between AGA-and SGA-infants of very low birthweight. III. Influence of postnatal age. AB - Seven very low birthweight (VLBW) infants, small for gestational age (SGA), with moderate intrauterine growth retardation and 7 VLBW-infants, appropriate for gestational age (AGA), fed breast milk fortified with 6 g freeze-dried human milk per 100 ml were studied on the 8th, 21st and 42nd days of life. The protein intake on the study days varied between 2.68 and 3.61 g/kg/day in the SGA-and 2.69 and 3.75 g/kg/day in the AGA-infants. Serum concentrations of total bile acids (BA) and the renal excretion of total nitrogen (TN) as well as alpha-amino nitrogen (AAN) were measured in all infants on each study day. On the 8th day of life a mean protein intake of 3.2 g/kg/day resulted in higher serum concentrations of BA as well as in a higher renal excretion of TN and AAN in the SGA-infants when compared to the AGA-infants. On the 21st day of life these differences were smaller and only the serum concentration of BA and the renal excretion of AAN were still significantly higher in the SGA-infants. On the 42nd day of life only serum concentrations of total BA were elevated in the SGA infants when compared to that in the AGA-infants. The observed metabolic differences between moderately SGA-and AGA-infants related to protein and bile acid metabolism diminished during the first weeks of life. The present data suggest that when nutritional management of VLBW-infants is planned, differences in metabolic capacities must be considered and protein intake should be increased with caution and in accordance to the individual metabolic situation of the infants during the first weeks of life. PMID- 2596274 TI - Acute gastroenteritis. Changing pattern of clinical features and management. AB - During seven epidemics of rotavirus from 1978 to 1987, 575 children younger than 3 years were admitted to hospital with acute gastroenteritis. The management before and during hospitalization, the status on admission and the outcome are reviewed. The mean age of the patients rose significantly during the study period, with the proportion younger than 12 months decreasing from 50 to 26%. Mild to moderate iso-osmolal dehydration was found in most cases, both hypernatraemia and hyponatraemia were rare. The home management had usually consisted of fasting except for "clear fluids". Oral rehydration and rapid feeding in hospital according to modern principles accelerated weight gain, shortened the duration of diarrhoea and the hospital stay and reduced the requirement for intravenous fluid therapy. This experience, together with the current rarity of acute gastroenteritis in young infants and of delay in recovery, suggests that oral rehydration and realimentation should be more extensively used in general practice. PMID- 2596275 TI - How do carriers of hemophilia experience prenatal diagnosis (PND)? Carriers' Immediate and later reactions to amniocentesis and fetal blood sampling. AB - A semistructured personal interview was performed with 29 carriers of hemophilia A or B, 1-5 years after a pregnancy in which prenatal diagnosis (PND) was performed by fetal blood sampling. Fetal blood sampling by fetoscopy was significantly more often reported by the women to the more trying than expected than was ultrasound-guided heart puncture. Of 29 women 13 was classified as having experienced the PND process (amniocentesis and fetal blood sampling) as distressing, having had mental or psychosomatic symptoms associated with it. All of the women who had abortion/miscarriage after PND reported a very high frequency of psychological sequelae during the 6 months that followed PND. Of 22 women who continued their pregnancy with a healthy fetus after PND 8 experienced the period until delivery as trying and felt that their emotional and somatic status influenced their daily life activities. This was particularly common among women who after fetoscopy received routine profylactic terbutalin treatment and had continuous sickleave until the 36th gestational week, 17/29 would consider going through PND in the future. Qualified psychological assistance must be offered both before and after PND. PMID- 2596276 TI - Paralytic ileus, a serious complication in acute diarrhoea disease among infants in developing countries. AB - Intestinal hypomotility is a common late complication in infants with acute diarrhoeal disease in pakistan. Among the infants admitted to our gastrointestinal unit with a history of acute diarrhoea, 35% developed abdominal distension and 12% developed the full clinical picture of paralytic ileus. The infants with ileus were treated with decompression and total parenteral nutrition; in this group the mortality rate was 25%. We compared 30 infants who developed ileus (group A) with an age-matched control group of infants (group B) who were admitted because of acute diarrhoea but did not develope ileus. The use of antimotility drugs was significantly more frequent in group A. Serum-K was not different in in group A (3.92 +/- 0.22 mmol/l) and group B (4.32 +/- 0.18 mmol/1). However, there were more patients who had serum-K below 3 mmol/l in group A (8/30) than in group B (5/30). We conclude that the use of antimotility drugs predisposes to the development of ileus in infants with acute diarrhoea. Hypokalemia may contribute to ileus in a few cases but is generally not a prerequisite. PMID- 2596277 TI - Peritoneal dialysis in the treatment of metabolic crises caused by inherited disorders of organic and amino acid metabolism. AB - Four neonates who presented with coma secondary to hyperammonaemia resulting in central respiratory failure were treated with peritoneal dialysis for between 16 and 120 hours. Underlying diseases were maple-syrup-urine disease, propionic acidaemia and citrullinaemia in two patients. Clinical improvement was observed in three patients within 16 to 72 hours after institution of peritoneal dialysis. Biochemical analysis revealed a rapid reduction in plasma concentration of leucine, isoleucine and valine as well as their alpha-keto-analogues in the infant suffering from maple-syrup-urine disease. Correction of ammonia, glycine, alanine and propionic acid concentrations was observed in the infant with propionic acidaemia 24-72 hours after institution of peritoneal dialysis. Severe hyperammonaemia (1,000-2,500mumol/l) in two infants with citrullinaemia before peritoneal dialysis was treated successfully in one infant; whereas the second infant showed no clinical improvement despite amelioration of biochemical parameters. Glucose-absorption from peritoneal dialysis solution was in the range of 216-441 mg/kg/h. PMID- 2596278 TI - Persisting glomerular hyperfiltration in short-term diabetic children without microalbuminuria. AB - The renal function in a group of diabetic children (n=29;age;4-17 yr; IDDM duration: 1,5-13 yr) was studied with a 3 year interval. At the first evaluation glomerular filtration rate (GFR) as assessed by inulin clearance was significantly increased compared to control values (167 +/- 32 vs. 124 +/- 18 ml/min/1.73 m2; pl less than 0.01). Eighteen out of 29 children exhibited a glomerular hyperfiltration (GFR greater than 160). Three years later mean GFR was identical (169 +/- 25 ml/min/1.73 m2) and 16 children were hyperfiltrating. Among them, 11 have had a persisting glomerular hyperfiltration over the 3-year period. Renal plasma flow (RPF) was positively correlated to GFR (r=0.7; p less than 0.01) and remained elevated at both evaluations (794 +/- 163 and 812 +/- 157 ml/min/1.73 m2, p greater than 0.01 vs, control values). When the children were separated into 3 groups according to IDDM duration no significant differences were observed in the results for GFR and RPF, Mean urinary albumin excretion was comparable at the 3-year interval, and not significantly different from the control values (5.2 +/- 3.7 and 8.2 +/- 6.6 respectively vs. 8.65 +/- 4 microgram/min). None of the children demonstrated a persistent microalbuminuria. This study reveals a high proportion of diabetic children with a persisting glomerular hyperfiltration, without any other symptom of incipiens nephropathy, If elevated GFR plays an important role in the development of diabetic nephropathy, this study emphasizes the value of regular evaluation of renal function in diabetic children. PMID- 2596279 TI - Long-term quality of life and psychosocial coping after treatment of solid tumours in childhood. A population-based study of 94 patients 11-28 years after their diagnosis. AB - In order to assess the long-term quality of life after childhood cancer, we examined and interviewed 94 survivors of childhood solid tumours (excluding brain tumors) diagnosed in our hospital between 1960 and 1976. Their follow-up times ranged form 10.7 to 27.7 years, and their ages at the time of this study form 11.3 to 41.5 years. The subjects had a higher educational level than the Finnish general population. Fewer of the females and as many of the males were married as in the general population. Eight healthy men had been rejected for military service because of the history of cancer. An unsatisfied desire to know more about their own medical history was evident. According to our findings, some subjects after childhood solid tumour are at risk of developing emotional and social problems. However, the great majority of the survivors were well balanced psychologically, living a normal social life and showing adequate capacity to cope. PMID- 2596280 TI - Valvuloplasty with large trefoil balloons for the treatment of congenital pulmonary stenosis. AB - Percutaneous balloon valvuloplasty was performed in 16 children, 1 1/2 to 14 years old, with congenital pulmonary stenosis with teh use or trefoil balloons. These balloons, which consist of 3 identical angioplasty balloons, do not interrupt completely the blood flow during inflation. The size of the trefoil balloons used was 30 to 50% larger than the valve anulus. A obtain an effective pulmonary valvuloplasty in two patients with large valve anulus. The mean prevalvuloplasty systolic gradient fo 78.2 +/- 28.9 mmHg (range 40 to 140 mmHg) was reduced to 20.3 +/- 5.7 (range 10 to 30 mmHg) after valvuloplasty. No patient developed significant hypotension or bradycardia or other complications as a result of the procedure. The findings demonstrate that percutaneous balloon valvuloplasty with oversized trefoil balloons effectively treated congenital pulmonary stenosis without complications in the cases studied. The use of large trefoil instead of single balloons of a similar diameter is advantageous since they cause no significant compromise of the cardiac output during valvuloplasty. PMID- 2596281 TI - Trunk asymmetry and scoliosis, Anthropometric measurements in prepuberal school children. AB - A total of 1060 children (515 girls, 545 boys) were examined for screening of trunk asymmetry ans scoliosis at an average age of 10.8 years. The physical examination consisted of height, sitting height, total arm length and leg length inequality determinations and moire topography. Trunk asymmetry was measured by forward bending test and a posteroanterior standing radiograph of the spine was taken of those 188 (17.7%) children who had a trunk hump greater than or equal to 6 mm. Only 20.1% of the children were found to be exactly symmetric in the forward bending test, 47.3% had a right-sided hump and 32.6% had a left-side hump. Humps of 6 mm or more were significantly (p = 0.03) more prevalent among girls (21.7%) than boys (16.3%). More fringe asymmetry was provided to be common: only 9% of the material was totally symmetric, two thirds has asymmetry of less than or equal to 1 fringe, 26.6% has asymmetry greater than 1 and less than or equal or 2 and 5.4% greater than 2. The prevalence of scoliosis (trunk hump greater than or equal to 6 mm and Cobb angle less than or equal to 10 degree) was 4.1%. The majority (72.1%) of the curves were left convex. PMID- 2596284 TI - High breath hydrogen baselines: a new diagnostic parameter? PMID- 2596283 TI - Transient hypogammaglobulinemia of infancy: Five new cases, review of the literature and redefinition. AB - The clinical and immunological data of 5 patients with transient h hypogammaglobulinemia of infancy (THI) are presented and compared to published data. In THI, there is distinction between patients who can mount a specific immune response, by producing specific antibodies to bovine serum albumin, diphtheria toxin, and isohemagglutinins, and patients with more severe forms of immunodeficiency. With only 5 reported cases of THI in 11 years and analysis of more than 8000 sera-, our data support the notion that THI is a relatively rare disorder. THI can only be diagnosed with certainty in retrospect, although the ability to mount an active, specific immune response is a strong indicator for the diagnosis. We propose a more accurate definition of THI to help avoid clinical misjudgement. PMID- 2596282 TI - Bacteraemia as predictor of HIV infection in African children. AB - In Rwanda, both HIV infection and bacteraemia represent major health problems among paediatric populations. We carried out of prospective study of determine if bacteraemia is a marker of HIV infection among ambulatory and hospitalized Rwandese children. All children presenting at the Department of Paediatrics of the Center Hospitalier de Kigali who had their blood cultured during a two-month period were eligible for the study. One hundred and thirty-five children were included in the study. A pathogen was isolated from 36 children (26.7%): S. typhimurium (10 cases), S. enteritidis (6), S. typhi (4), Str. pneumoniae (9). H. influenzae (6) and S. aureus (1). No association was found between bacteraemia and HIV seropositivity when all the children were considered. However, among patients less than 2 years old, bacteraemic subjects were more frequently (p less than 0.05) HIV seropositive (44%) than those with negative blood cultures (19%). Our study shows that in young children in Central Africa, the presence of bacteraemia may be an important marker of HIV seropositivity. PMID- 2596285 TI - 1--(13)C-octanoate oxidation, energy expenditure and vitamin B2 supplement in premature infants. PMID- 2596286 TI - Bile peritonitis in the newborn. PMID- 2596287 TI - Incidence of celiac disease in a cystic fibrosis population. PMID- 2596288 TI - Congenital chylothorax and persistent pulmonary hypertension of the neonate. AB - In case of congenital chylothorax, an associated persistent pulmonary hypertension was a severe complication which has not hitherto been described. Recurrence of the chylothorax with the introduction of regular formula is also reported. PMID- 2596289 TI - Sandifer syndrome reconsidered. AB - Three children with Sandifer syndrome are described. One patient was at first erroneously diagnosed as having neurological disease; the two others had true neurological damage, which led initially to misinterpretation of their bizarre dystonic features. Awareness of this entity will spare such children needless investigations and suffering, while giving them the benefit of proper treatment. PMID- 2596290 TI - Severe acidosis in a neonate with pulmonary valve stenosis: a possible stress inducer of a fatal syndrome of fructose-1, 6-biphosphatase and aldolase deficiency. AB - A neonate is described whose clinical condition rapidly and irreversibly deteriorated on day two. He developed a profound acidosis, hypoglycaemia and a shock-like syndrome. The infant was centrally cyanosed and had a systolic murmur from a moderately severe pulmonary valve stenosis and a small atrial septal defect. The overwhelming acidosis was inconsistent with the severity of the congenital heart defects and as no infection was found a metabolic cause was sought. Liver tissue obtained at autopsy shortly after death on day four, showed deficiencies of fructose-1, 6-biphosphatase and aldolase. PMID- 2596291 TI - Esophageal atresia complicating the Goldenhar anomalad. AB - A 2200 g male infant was found to have esophageal atresia and esophageal fistula in addition to truncus arteriosus and oculo-auriculo-vertebral dysplasia. The presence of facial asymmetry in an infant with esophageal atresia should prompt a search for additional anomalies before surgery is contemplated. PMID- 2596292 TI - Oculocerebral hypopigmentation syndrome (Cross syndrome) in a Gipsy child. AB - A boy aged 2 years, born prematurely to Gipsy parents, presented with hypopigmentation severe encephalopathy with athetoid movements, bilateral ocular anomalies including cloudy corneas, iris atrophy and cataracts, as well as dental defects. Ultrastructural examination of the skin disclosed scare melanosomes. Although the neurologic and ocular anomalies might have been accounted for by his extreme prematurity, their association with hypomelanogenesis and dental defects support, in this patient the diagnosis of the oculocerebral hypopigmentation syndrome (Cross syndrome). PMID- 2596293 TI - Human immunodeficiency virus-associated thrombocytopenia in infants. AB - Severe thrombocytopenia was the initial manifestation of human immunodeficiency virus infections in 5 infants under 15 months of age. In only 2/5 cases maternal seropositivity was previously known while in the other 3 it was discovered after onset of the infants' thrombocytopenia. One infant died, due to intracranial hemorrhage, and the other 4 developed to disease stage IV. Human immunodeficiency virus infection must be considered in the diagnosis of thrombocytopenia. PMID- 2596294 TI - Outcome after cessation of therapy in childhood leukemia. A population-based Nordic study of 986 patients. PMID- 2596295 TI - Effects of synthetic salmon calcitonin on C cells of the thyroid. AB - The effects of long-term administration of synthetic salmon calcitonin (TZ-CT) on thyroid C cells of rats were evaluated immunohistochemically and electron microscopically. Low dose (0.075, 0.75 and 7.5 IU/kg/day) administration caused no significant changes in the C cell population, whereas high doses (30 and 120 IU/kg/day) caused C cell suppression. The area ratio of C cells to total cells in the thyroid was measured on sections immunoperoxidase stained for calcitonin. The average C cell ratio was compared among the experimental groups. This morphometric analysis of the high-dose and control groups confirmed the differences in C cell populations statistically (30 IU/kg vs. control, p less than or equal to 0.05; 120 IU/kg vs. control, p less than or equal to 0.05). The suppressive effect of TZ-CT on C cells was reversible after cessation of administration for one month. Electron microscopic examination on the C cells in the high-dose groups revealed no particular ultrastructural differences. These results may suggest a negative feedback mechanism on C cells by exogenous CT. PMID- 2596296 TI - Morphometric changes in glomerular anionic sites during aminonucleoside nephrosis. AB - Changes in glomerular anionic sites were examined morphometrically in nephrotic rats receiving daily subcutaneous injections of puromycin aminonucleoside (PAN). The high-iron diamine-thiocarbohydrazide-silver proteinate method showed that anionic sites composed of heparan sulfate proteoglycans formed a continuous band within the lamina rara externa of the glomerular basement membrane (GBM) in control rats. Only one day after the first injection of PAN, anionic site loss was already detectable, preceding the morphological changes in the epithelial cells. The number and size of the anionic sites decreased greatly between days 7 and 10, when urinary protein excretion began to appear. The number of anionic sites in the paramesangial regions (epithelial side of the mesangium) was slightly more reduced than that in the capillary walls. These results suggested that PAN directly injured the glomerular anionic sites and increased the permeability of the glomerulus to macromolecules. However, there was no complete correlation between the number of lost anionic sites and the level of urinary protein excretion. Thus protein excretion into the urinary space may be related not only to the loss of subepithelial anionic sites but also to dysfunction of the protein absorption mechanism in epithelial cells due to excessive permeation of macromolecules through the GBM. PMID- 2596297 TI - Gallstones in gallbladder diseases. AB - The correlation between gallbladder stones (gallstones) and various gallbladder diseases was examined. The incidence of gallstones was 47.1% in cases of non neoplastic epithelial polyp, 48.0% in adenoma, and 59.1% in adenocarcinoma. There was no relation between the incidence of gallstones and sex. The incidence of gallstones in cancer cases showed no difference among histological gradings. Non neoplastic epithelial polyps, adenomas and carcinomas were divided into metaplastic type and non-metaplastic type based on the presence or absence of metaplastic changes. Comparison of the incidence of gallstones showed that cases of metaplastic-type polyp and adenoma had a higher incidence of gallstones than non-metaplastic-type polyp and adenoma. In the cases of cancer, no differences were observed in the incidence of gallstones between metaplastic-type and non metaplastic-type carcinomas. However, comparison among early carcinomas showed that metaplastic-type carcinoma had a significantly higher incidence of gallstones than the non-metaplastic-type. These results suggest that gallstones may play an important role in the histogenesis of gallbladder diseases of the metaplastic type. PMID- 2596298 TI - Pathology of the liver in "idiopathic portal hypertension" associated with autoimmune disease. The Ministry of Health and Welfare Disorders of Portal Circulation Research Committee. AB - The histopathology of the liver in idiopathic portal hypertension (IPH) associated with autoimmune disease (15 cases), was examined and compared with that of IPH without autoimmune disease (31 cases). It was found that hepatic histopathology was heterogeneous in the cases with autoimmune disease. That is, the hepatic histopathology in 7 cases was similar to that of classic IPH without autoimmune disease, and the remaining 8 cases disclosed unusual lesions such as focal non-suppurative cholangitis, nodular parenchymal hyperplasia, moderate portal inflammation, and intrahepatic ductopenia. These unusual lesions, which frequently coexisted in the same case, were not typical ones for making other diagnoses such as primary biliary cirrhosis or nodular regenerative hyperplasia of the liver. These findings suggest that unusual histologic lesions in the livers of IPH patients with autoimmune disease may represent an accentuated immunologic reaction inherent in IPH, or that such cases may be an abortive or incomplete form of primary biliary cirrhosis or nodular regenerative hyperplasia of the liver. PMID- 2596299 TI - Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. Report of an autopsy. AB - We present an autopsy report on a 14-year-old girl with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), placing emphasis on the mitochondrial enzymatic histochemistry of the 3 types skeletal muscle and cardiomyocytes. Generalized muscular atrophy, cardiac hypertrophy, cerebral cortical laminar necrosis, basal ganglia calcification and liver steatosis were observed. In the skeletal muscles, modified Gomori's trichrome staining demonstrated scattered ragged red fibers, and histochemical staining for mitochondrial enzymes showed intense positivity in the subsarcolemmal zones of some muscle fibers. Some of the hypertrophic cardiomyocytes also showed a ragged red appearance with the modified Gomori's trichrome stain. Histochemical staining for mitochondrial enzymes showed patchy loss of enzymatic activity in the myocardium. Electron microscopically, extreme accumulation of enlarged mitochondria and severe loss of myofibrils was observed in both skeletal muscle fibers and cardiomyocytes. The arteriolar smooth muscle cells also showed a mild increase in mitochondria. PMID- 2596300 TI - Indirect potentiometric titration of reducing carbohydrates. I. Using alkaline potassium mercuric bromide solution and sulphide selective electrode. AB - Indirect potentiometric titration of reducing carbohydrates was developed, where sugar is heated with excess of alkaline Hg(II)-bromide solution. The end point is detected potentiometrically using sulphide selective electrode. The effect of the alkalinity of the reagent, the heating period in a boiling water bath and the presence of the sucrose were studied. The statistical analysis of the results obtained by this method reveals that it can be used with the same accuracy as the Fehling' method. PMID- 2596301 TI - [Colorimetric determination of isoniazid in aqueous solutions and biological fluids]. AB - Method has been developed for determination of tuberculostatic isoniazid in aqueous solutions and biological fluids. The principle of the method is that hydrazine group of isoniazid reacts with 1-fluoro-2,4-dinitrobenzene forming a red chromophor in alkaline medium. The absorbency maximum of the chromophor is at 530 nm. Biological fluids were deproteinized and diluted with acetonitrile then adjusted to pH = 8.2 with trometamol-hydrochloric acid buffer and reacted with 1 fluoro-2,4-dinitrobenzene dissolved in acetonitrile. The chromphore was measured colorimetricaly against a blank solution which did not contain isoniazid. The method was calibrated in the range of 1-30 mg/l isoniazid and reproducibility was checked with recovery % determinations. PMID- 2596302 TI - [Hydrophobic constant values (delta RM0) of functional groups. I. Comparative study of delta RM0 values determined in open (TLC) and closed (OPTLC) chromatographic systems]. AB - delta RM0 values of functional groups (methyl, ethyl, n-propyl, methylene, phenyl, benzyl, saturation) of nitrogen bridgehead compounds [PP = pyrido(1,2-a) pyrimidine, THPP = tetrahydropyrido(1,2-a)-pyrimidine, CTM-PP = 2,3 cyclotrimethylpyrido(1,2-a)-pyrimidine, CTM-THPP = 2,3 cyclotrimethylenetetrahydropyrido(1,2-a)-pyrimidine, CTRM-PP = 2,3 cyclotetramethylenepyrido(1,2-a)-pyrimidine, CTRM-THPP = 2,3-cyclotetramethylene tetrahydropyrido(1,2-a)-pyrimidine, CTRM-THPP = 2,3-cyclotetramethylene tetrahydropyrido(1,2-a)-pyrimidine, THPQ = tetrahydropyrroloquinazoline-, HHAQ = hexahydroazepinoquinazoline-derivates have been calculated from difference of retention values measured on RP-di-C1 stationary phase using methanol + water mobile phases of 6 (10 respectively) various compositions and of retention values (RM0) extrapolated to 0% organic phase. Retention data have been determined in normal chambers loaded with change of phase rate because of the vapour space of the developing chamber and in so-called pressurized ultramicro chamber which is free of change of phase rate and that of vapour space, respectively. It has been ascertained that delta RM0 values of same functional groups--that had been measured in the two different chamber systems--have not significantly differ from each other. It has also been established that opposite direction distortions of RM0 values--measured in normal chambers with mobile phases nearing or moving off 0% organic phase--have generally similar effects on delta RM0 values which are free of change of phase rate. Significant investigations were carried out by programs written on TEXAS SR-52 computer and work has always been done in 95% confidence interval. PMID- 2596303 TI - [Rheologic investigation of electrode gels. II. Mechanical and thermal stability]. AB - In the publication consisting of 3 parts nine electrode gels have been investigated six of them are used in hospital pharmacies of this country. Character and stability of gel structure have been studied and controlled by rheological methods. Structural forces have been numerically characterized with maximum and equilibrium viscosity, values of "M and B coefficients" and directional tangents of viscosity curves. Mechanical and thermal stability have been determined, changes for six months storing have been studied by means of all rheological parameters, respectively. Besides investigating rheological parameters electric conductivity values--which are important in respect of practical use of electrode gels--have been determined too. On the basis of results Carbopol "G" designated gel has been found to be the best its use has been proposed not only in supersonic tests but also in ECG. PMID- 2596304 TI - Proceedings of the Second International Symposium on Gastrointestinal Cytoprotection. October 15-16, 1987, Pecs, Hungary. PMID- 2596305 TI - Gastric and cardiac organoprotection by lidocaine. AB - The concept of cytoprotection has been applied to many tissues afforded protection by drugs or endogenous chemicals against organelle, cyto- or histopathologic damage. We review here the "organoprotection" by lidocaine in rats and dogs as appraised by in vitro, ex vivo, and in vivo experiments with the stomach and heart, and as revealed at organelle to organ functional levels. Gastric mucosal lesions induced by 80% ethanol with 100 mM HCl on the ex vivo rat stomach were significantly reduced by lidocaine (2.2-4.4 mg/kg bolus followed by 66-132 micrograms/kg/min i. v. infusion). In anesthetized dogs with gastric corporeal lesions induced by increased gastric intraluminal pressure (50 mm Hg, 2.5 hrs), lidocaine (2.2 mg/kg bolus plus 66 micrograms/kg/min infusion) significantly reduced lesion severity. In the isolated rat heart, reperfusion after a 60 min period of ischemia induced localized cardiac mitochondrial swelling and disruption in ventricular apices which was greatly reduced if hearts were pretreated (15 min perfusion with lidocaine). In intact rats subjected to hemorrhagic shock, lidocaine pretreatment also facilitated shock resuscitation and reduced ultrastructural damage. In these diverse experiments, lidocaine organoprotection was likely mediated in part through reduction of ischemia induced organelle membrane damage and through reduction of reperfusion-induced superoxide and other oxygen-derived free radical related damage. PMID- 2596306 TI - The effect of some anti-ulcer agents on the early vascular injury of gastric mucosa induced by ethanol in rats. AB - The effect of some gastroprotective agents cysteamine, sodium salicylate, atropine, cimetidine, and pyrido-pyrimidine derivatives, rimazolium, Ch-127 and a mast cell stabilizer, BMY-26517-31 was studied on the enhanced vascular permeability of gastric mucosa induced by 100% ethanol, on the enhanced vascular permeability of peritoneal blood vessels due to 0.3% acetic acid and on carrageenin edema test. We found that cysteamine, sodium salicylate, rimazolium and BMY-26517-31 inhibited the alcohol-induced enhanced vascular permeability. They also decreased the carrageenin-induced edema and--with the exception of BMY 26517-31--the acetic-acid-induced enhanced vascular permeability of the peritoneal vessels. These results suggest that similar events are present in the early phase of acute inflammation and chemically induced mucosal lesions. Consequently, antiinflammatory activity might play role in the protective mechanism of some anti-ulcer agents. PMID- 2596307 TI - In vitro electrophysiological effects of cimetidine, prostaglandin E2 and acetylcholine on the rabbit gastric mucosa. AB - The electrophysiological effects of cimetidine, cytoprotective dose of prostaglandin E2 (PGE2) and acetylcholine were determined in parallel in Ussing chambered rabbit fundic and antral mucosal preparations. In the fundic mucosal preparations both cimetidine and PGE2 caused an increase in transmucosal potential difference (PD) and in short-circuit current (ISC); the transepithelial resistance (Rt) was essentially unchanged. Addition of acetylcholine to the pretreated fundic preparations produced further gradual increases in PD and ISC; cimetidine pretreatment delayed this effect of acetylcholine. In contrast to fundic mucosa, cimetidine did not cause any electrical change of the antral preparation but decreases in PD, Rt and ISC were detected after the addition of PGE2. Acetylcholine produced a rapid initial PD elevation followed by a PD drop of both antral tissues independent of pretreatment. These findings suggest that both cimetidine and PGE2 generated electrical hyperpolarisation of rabbit fundic mucosa. These changes may be favourable for mucosal protection. No "beneficial" electrical changes were detected on the antral mucosa after administration of cimetidine and PGE2. Acetylcholine increased the effects of other stimuli on the fundic mucosa. In the rabbit antral mucosa acetylcholine generated biphasic changes of electrical properties. PMID- 2596308 TI - An unusual stress-induced gastric lesion. AB - An unusual type of gastric lesions, clearly different from erosions, was produced in rats by prolonged immobilization and application of adrenaline at the first and the third hour of stress. The lesions are large, round, highly hyperaemic elevations of the glandular part of the rat stomach. Necrosis of the superficial 2/3 of the mucosa with haemorrhages and leucocytic infiltration as well as marked oedema, focal haemorrhages, necrotic vasculitis and darkly stained phagocytes in the submucosa are the most prominent histological features of it. Some special conditions seem to be necessary for the development of this "superficial gastric necrosis". PMID- 2596309 TI - Naloxone exerts a dose-dependent gastric cytoprotective effect. AB - Previous work has shown that naloxone inhibits the ulcerogenic effects of indomethacin and stress, although the site, mechanism or dose are unknown. We investigated whether naloxone possessed gastric cytoprotective properties, generating a dose-response curve existed for both intragastric (IG) and intravenous (IV) administration. One hundred and two rats were subjected to a four hour period of restraint, with the last two hours at 4 degrees C. Naloxone was given hourly during restraint at doses of 0 (Control), 1, 5, 10, 20 mg/kg. After sacrifice, the residual gastric volume, and pH were measured and the number of mucosal lesions scored. The cytoprotection offered by naloxone was different from control (p = 0.0001), with the intravenous route having a greater effect (p = 0.038). While this protective effect did not correlate with changes in gastric acidity, it correlated with the dose of naloxone. PMID- 2596310 TI - The effect of norepinephrine on the incidence of stress-induced gastric erosions. AB - The number of gastric erosions induced experimentally by immobilization stress were observed following norepinephrine treatment. We revealed a significant reduction of the number of erosions. This indicates the protective effect of sympathetic nervous system in the pathogenesis of stress-induced erosions. PMID- 2596311 TI - Effect of atropine, PGF2 alpha and cimetidine on the beta-carotene induced cytoprotection in ethanol-treated rats. AB - The aim of the study was to evaluate the influence of atropine, PGF2 alpha and cimetidine on the gastric cytoprotective effect of beta-carotene. Mucosal damage was produced by intragastric (i.g.) addition of 96% ethanol in CFY-strain rats of both sexes weighing 180-220 g. Gastric cytoprotection caused by i. g. pretreatment with 1.0 mg/kg beta-carotene 30 minutes before ethanol administration, was observed after 1 hour. Atropine (0.5 mg/kg), cimetidine (50 mg/kg) and PGF2 alpha (200 micrograms/kg) were given intraperitoneally (i.p.) 30 minutes before ethanol administration with and without beta-carotene and the changes in the number and severity of the gastric ulcers were detected. PGF2 alpha did not influence the gastric cytoprotective effect of beta-carotene meanwhile it was inhibited by atropine and markedly by cimetidine. Deleterious effect of cimetidine on the beta-carotene-induced cytoprotection may be explained perhaps by the adverse effect of the two compounds on ATP-cAMP transformation hereby counteracting one another, but more data are needed to the better understanding of drug interactions relating to mucosal cytoprotection. PMID- 2596312 TI - Effect of cytoprotective and antiulcer drugs on the healing process of subacute gastric ulcer in rat (a new model). AB - It has been developed by us a simple new method for producing subacute gastric ulcer in rats, combined with a novel method for the quantitative evaluation of the healing process. Fasted rats with 120-150 g were used. The animals were anaesthesized by ether and than a polyethylene chateter was orally inserted into the stomach with a fine needle inside. After the cannule reached the gastric wall, the needle was pressed gently so as to punch the gastric wall. Drugs under study were administered orally 30 min and 24 h after the puncture. Food and water were given ad libitum from 2 h after the intervention until the end (96 h) of experiments. In order to follow the healing process of subacute ulcer, the so called tensile strength of the ulcer was determined by inflating and expressed in mmHg. The healing rate was calculated. The antiulcer drugs: Cimetidine, Famotidin, Pirenzepine and sucralfate dose dependently and significantly increased the healing rate of ulcer. Non steroidal antiinflammatory drugs: naproxen, piroxicam, indomethacin and ibuprofen significantly delayed the healing of ulcer. ASA showed tendency to delay the healing. Strong HCl (0.5 molar) significantly delayed the healing of ulcer. N-EM given subcutaneously dose dependently delayed the healing of subacute ulcer. PMID- 2596313 TI - Effects of chronic and subchronic treatment with antiulcer drugs in repairing rat gastric mucosa experimentally and chronically damaged. AB - An experimental model concerning the development of chronic gastric mucosa damage in rat is proposed making it possible to evaluate both the preventive and curative properties of a number of antiulcer drugs. Furthermore, the possible modification of the sensitivity to a stimulus regulating gastric functions after a prolonged administration of antiulcer drugs is assessed. PMID- 2596314 TI - The role of gastric and duodenal pH in the cysteamine-induced duodenal ulcer in the rat. AB - Many secretory studies reported an increase in gastric acid secretion by the duodenal ulcerogen cysteamine. A detailed analysis of these experiments, especially the results from rats with chronic gastric fistula suggest that direct stimulation of gastric acid secretion may not be the primary mechanism of the duodenal ulcerogenic action of cysteamine. We used a different approach and measured the pH at the site of ulceration in the proximal duodenum. A duodenal ulcerogenic dose of cysteamine did not change the pH at the anterior or posterior wall of the duodenum during 4 hr. In the same dose and by the same route of administration, cysteamine nevertheless induced duodenal ulcers in 24 hr. These experiments demonstrate that in addition to the effect on gastric acid secretion, other factors are needed to the effect on gastric acid secretion, other factors are needed to explain the early duodenal ulcerogenic action of cysteamine. PMID- 2596315 TI - Role of passive HCO3(-)-diffusion in duodenal acid-stimulated alkaline secretion. AB - We investigated acid-stimulated alkaline secretion (AS) under different luminal acid concentrations and its relation to mucosal damage on isolated proximal rabbit duodenal mucosa. Luminal HCl caused an increase of AS depending on their concentration, and it was not specific for acid, but occurs also with luminal ethanol. Histology showed [H+]-dependent mucosal damage ranging from villus tip lesions to deep mucosal injury. Ouabain- and/or anoxia-sensitive (active) AS constituted 80% and 100% respectively of basal AS. After exposure to various luminal acid concentrations passive diffusion (sensitive only to removal of nutrient HCO3-) was solely responsible for the rise in AS. We conclude that in the in vitro rabbit duodenum passive diffusion of HCO3- associated with increasing mucosal damage is the major component of the rise in AS. PMID- 2596316 TI - The role of Brunner's glands in the mucosal protection of the proximal part of duodenum. AB - In the course of a prospective study authors examined the role of the hyperplasia of Brunner's glands in the mucosal protection of proximal part of duodenum in patients with peptic ulcer, chronic pancreatitis and chronic renal insufficiency. Their method for this study was the histological examination of the endoscopic biopsy specimens. The hyperplasia of Brunner's glands occurs with significant frequency in all the three examined groups of patients, while we found it less frequently in the controls. Hyperplasia of Brunner's glands is one of the protective mechanisms of the organism, which serves the protection of the duodenal mucosa between the pyloric ring and the papilla of Vater, against the damaging effect of the hydrochloric acid. PMID- 2596317 TI - Prevention of non-steroidal anti-inflammatory agents induced acute gastric mucosal lesions by carbonic anhydrase inhibitors. An endoscopic study. AB - The present paper studies the effect of acetazolamide, an inhibitor of carbonic anhydrase, on acute gastric mucosal damage induced by non-steroidal anti inflammatory drugs. The study was performed on healthy male subjects. The drugs tested were aspirin (1.5 g/day), indomethacin (75 mg/day), phenylbutazone (600 mg/day) and ibuprofen (600 mg/day) given for 7 days in 3 divided doses. Each drug was given to 5 cases in two separate periods, during which they were given acetazolamide 20 mg/kg/day or placebo in random order. Dyspeptic symptoms were evaluated. Endoscopy was performed before, and 3 and 7 days after NOSAC administration. Gastric mucosal lesions were evaluated according to the scale proposed by Lanza (J. Clin. Pharmacol., 24: 1984, 89) and the severity of the lesions was calculated. All drugs tested produced dyspeptic symptoms and acute mucosal damage of the gastric mucosa. Inhibition of gastric mucosa carbonic anhydrase by acetazolamide cessated promptly dyspeptic symptoms and reduced significantly the number and severity of drug-associated mucosal lesions. PMID- 2596318 TI - Liver cell protection in toxic liver lesion. AB - Most of the hepatoprotective drugs belong to the group of free radical scavangers. The mechanism of their action involves membrane stabilisation, neutralisation of free radicals and immunomodulation. The authors demonstrate the effect of different-drugs used in therapy of liver diseases (silymarin, silibinin, Aica-P) in human clinico-pharmacological study and in animal experiments. A wide number of methods was used. Both the silymarin preparates and the Aica-P corrected the altered immunreaction and the decreased superoxid dismutase (SOD) activity of erythrocytes and lymphocytes in patients with alcoholic liver cirrhoses. The scavanger effect of these drugs was demonstrated in the subcellular fractions of liver cells in animal experiments. The data support the therapeutic effect of these drugs in liver diseases. PMID- 2596319 TI - Drug metabolism in drug-induced liver diseases: pathogenetic role of active metabolites. AB - Three cases with drug-induced liver diseases (hepatitis caused by hydralasine, steatosis caused by methimazole, choletasis caused by birth control pill) were investigated with respect to their drug metabolising ability. Clinical diagnoses were based on the exclusion of other pathogenetic factors, on histological findings of liver biopsy specimens and on the clinical chemical tests. Investigation of biotransforming ability was carried out using test materials (menthol loading, antipyrine, sulfadimidine, caffeine, indocyanine green kinetics) and measurement of D-glucaric acid excretion. In all cases the results show a defective capacity in some respect of drug metabolism. Possible pathogenetic role of reactive metabolites is discussed in the pathomechanism of genesis of drug-induced liver diseases. PMID- 2596320 TI - Effect of treatment with submaximal and excessive doses of caerulein on pancreatic growth in newborn rats. AB - Different groups of CFY female newborn rats were treated with saline, or 1 microgram/kg or 100 micrograms/kg doses of caerulein given s. c. 3 x/day. Application of 100 micrograms/kg dose of caerulein for 3 days stimulated pancreatic growth inducing pancreatic hyperplasia; both (1 and 100 micrograms/kg) doses evoked increase in trypsin/DNA ratio inducing pancreatic hypertrophy in 4 days-old rats. Using the indices as before application of 1 microgram/kg caerulein for 10 days stimulated pancreatic growth and both (1 and 100 micrograms/kg) doses elicited glandular hypertrophy in 11-days-old rats. In 24 old-rats the 1 microgram/kg doses of caerulein given for 3 days stimulated pancreatic growth and induced pancreatic hypertrophy, the 100 micrograms/kg doses of the peptide given for 3 days, however, evoked pancreatic aplasia and atrophy. PMID- 2596321 TI - In vitro method for measurement of free radical effects: effect of PMS (phenazine methosulphate) on red blood cell membrane. AB - The aim of this study was to elaborate a simple in vitro model for rapid and quantitative measurement of free radical effects. Free radical generating characteristics of PMS were measured in the case of red blood cell (RBC) membrane. The mechanism of free radical action was investigated in MgCl2, CaCl2, BaCl2 and in Verapamil HCl medium. The most important result of the investigations is as follows: Membrane damage of RBC provoked by the mechanism of free radical generation of PMS is proportional to the intracellular K+-efflux and to the extracellular Na+-influx. The PMS dependent K+-efflux in a NaCl containing medium in the presence of CaCl2 increases significantly, while it remains unchanged in MgCl2 medium. The PMS dependent K+-efflux and Na+-influx were considerably decreased by Verapamil HCl in NaCl containing solution. We have come to the conclusion that new, non-selective pores are formed in the membrane. The measure of the damage increases in the presence of Ca2+ions and decreases in the medium containing Verapamil HCl. PMID- 2596322 TI - The free radical mechanisms in beta-carotene induced gastric cytoprotection in HCl model. AB - The aims of our experiments were to clear up the possible correlations between the free radical mechanisms and the gastric cytoprotection of beta-carotene on HCl-induced gastric mucosal lesions. The beta-carotene was intragastrically given in doses of 1 and 10 mg/kg and 30 min. later 1 ml 0.6 N HCl was given to provoke the mucosal damage. After 1, 5, 15, 30 and 60 min. the animals were sacrificed. The number and severity of gastric mucosal lesions were calculated. The superoxide dismutase (SOD), glutathion peroxidase (GPX), catalase (CAT) activity and the malondialdehyde (MDA) and reduced glutathion (GSH) contents were determined from the gastric mucosa of rats. It was found that 1. beta-carotene was able to reduce the number and severity of ulcers only after 30 min.; 2. the CAT activity was decreased at 60 min. by carotene; 3. the GPX activity became dissimilar in the different groups after 15 min; 4. the changes of GSH were found to be similar ones; 5. the SOD activity was lower during the cyto-protection; 6. the MDA level remained practically unchanged. It has been concluded that 1. the free radicals are the consequences of the development of gastric ulcer and cytoprotection; 2. the scavenger character of beta-carotene is involved in its cytoprotective effect. PMID- 2596323 TI - Role of oxygen-derived free radicals in hemorrhagic shock-induced gastric lesions of rats. AB - This study was designed to determine whether oxygen-derived free radicals play a role in the pathogenesis of gastric lesions produced by hemorrhagic shock in the rat. Allopurinol (Zyloric), an inhibitor of xanthine oxidase (responsible for the formation of superoxide radicals) and MTDQ-DA (Kontrad), a synthetic antioxidant of dihydroquinoline type were used. In the anesthetized rat 0.1 N HCl was instilled into the stomach and the rat was bled to reduce the blood pressure to 30 mmHg for 20 min. The blood shed was retransfused. Twenty min later the stomach was removed. The area of gastric mucosal lesions were measured, the activity of endogenous peroxidase was examined histochemically and a histological grading was made. Both allopurinol and MTDQ-DA significantly protected against hemorrhagic shock-induced gastric lesions and peroxidation. These results suggest that oxygen derived free radicals play an important role in the formation of gastric lesions produced by ischemia plus 0.1 N HCl. PMID- 2596324 TI - Intestinal post-ischemic reperfusion injury: studies with neonatal necrotizing enterocolitis. AB - In the feline intestine studies have implicated superoxide (O.-) and other oxygen derived free radicals as initiators of injury as measured by increased capillary permeability during the reperfusion period. Biochemical mechanisms of this free radical generation include: xanthine oxidase dependent O.- production, hydrogen peroxide (H2O2) formation by superoxide dismutase (SOD), hydroxyl radical (OH-) production via the Haber-Weiss reaction, and lipid radical formation from membrane peroxidation. Pathological consequences of these events include inflammatory neutrophil infiltration, damage to the collagen and mucosal basement membrane, increased capillary permeability, edema, cell degeneration and necrosis. Animal models of neonatal necrotizing enterocolitis (NNEC) indicate that intestinal injury occurs after the etiologic factors (hypothermia, hypoxia) are removed. In order to determine the role of active oxygen species in the pathogenesis of NNEC, weanling hamsters and neonatal piglets were cold stressed and activities of pro/antioxidant enzymes were determined, and histopathologic and ultrastructural studies were performed. Cold stressed weanling hamsters showed a 55.7% (P less than 0.05) decrease in xanthine dehydrogenase/xanthine oxidase activity ratio. Light microscopy revealed scattered colonic mucosal erosions and submucosal edema in 50% of cold stressed animals. Transmission electron microscopy demonstrated degeneration of colonic mucosal epithelial cells, enlarged intracellular spaces, cytoplasmic vacuolization, and nuclear membrane swelling. The colonic serosa was also edematous and infiltrated with bacteria. Large intestinal tissue from cold stressed neonatal piglets showed a significant increase (P less than 0.05) in Mn and Cu, Zn, SOD, CAT, GSH-Red, total GSH, and Glc6-PD at 0 and 12 hrs. post stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596326 TI - Abstracts. IUPS satellite symposium, Sympathetic control of cardiovascular function. Integration of animal and human studies. Goteborg, Sweden, July 7-8, 1989. PMID- 2596325 TI - Expert systems in medicine. AB - The emergence of the artificial intelligence (AI) in computer technology and its application in the medical field enables the researchers to carry out such intelligent activities like image processing, medical reasoning systems, clinical decision supporting and natural language understanding, etc. A gastroenterological expert system application is briefly demonstrated in this paper. Similar expert systems can be seen to be useful in the research of gastrointestinal cytoprotection, including the plan of different compounds with cytoprotective effect, experimental and clinical medical research. PMID- 2596327 TI - The cold pressor test: effects on sympathetic nerve activity in human muscle and skin nerve fascicles. AB - Micro-electrode multi-unit recordings of muscle nerve sympathetic activity (MSA) involved in cardiovascular homeostasis or skin nerve sympathetic activity (SSA) involved in thermoregulation were made in the right peroneal nerve of 48 healthy volunteers during performance of the cold pressor test, i.e. immersion of one hand in ice water (2 +/- 0.5 degrees C) for 1 min. Eleven subjects underwent the same procedure on a second MSA recording occasion. As a rule, immersion evoked an increase in MSA, with a gradual decrease on emersion. The response showed a wide range of variation between and within subjects; the intra-individual difference between first and second immersion on the same recording occasion was up to sevenfold, and from first to second recording up to fivefold. The increase in MSA correlated with the degree of discomfort from the ice water. In nine subjects with a large increase in MSA on ice water immersion, intracutaneous painful electrical stimulation to a level equalling the discomfort from the ice water was added, but it was not accompanied by any change in MSA. The increase in MSA was accompanied by and correlated quite well with an increase in blood pressure. Intra-arterial blood pressure recordings showed that MSA occurred at pressure levels normally associated with total inhibition of MSA, and that an inverse linear relationship between diastolic blood pressure and MSA at rest was abolished during the ice water immersion. SSA showed no consistent change with ice water immersion. It is concluded that the cold pressor test is a powerful activator of MSA, i.e. baroreceptor-governed vasoconstrictor outflow; that MSA contributes to the blood pressure elevation with this manoeuvre; that MSA operates at another blood pressure level during the manoeuvre and that the baroreflex inhibitory level consequently is changed; and that the response is not a reaction to pain only. PMID- 2596329 TI - The metabolic relation between hypoxanthine and uric acid in man following maximal short-distance running. AB - This study was performed to assess the metabolic relation between hypoxanthine and uric acid following short-distance maximal running. Eleven trained males, mean age 22 years (16-31), were instructed to run 800 m in the shortest time possible. Blood samples were collected before warm-up, before the run, immediately after the run and periodically up to 24 h following the run. Blood lactate was determined after warm-up, and at 5, 10, and 30 min following the run. Mean VO2 max for the subjects was 65.8 (4.7) (SD) ml kg-1 min-1 and mean oxygen demand for the running was 118 (8)% of VO2 max. Plasma hypoxanthine levels rose from 3.3 (1.4) to a peak of 48.2 (19.0) mumol l-1 at 20 min following the run and at 180 min had almost returned to pre-run levels. Plasma uric acid levels rose from a pre-run value of 267 (34) to a peak value of 431 (87) mumol l-1 at 45 min following the run. Uric acid concentrations had not returned to normal at 10 h following the run. The blood lactate level peaked at 5 min with 13.7 (2.0) mmol l 1. The results obtained in this study indicate a metabolic relationship between the formation of hypoxanthine and the formation of uric acid. The data also indicate that xanthine oxidase is active following short-distance intensive running. PMID- 2596328 TI - Changes of high-energy phosphorous compounds in skeletal muscle during glucose induced thermogenesis in man. A 31P MR spectroscopy study. AB - By the use of invasive techniques, skeletal muscle has been shown to contribute to thermogenesis induced by glucose in humans. In an attempt to study this phenomenon by a non-invasive method, this study investigated intracellular high energy phosphorous compounds in calf muscle by 31P MR spectroscopy during an oral glucose load in healthy lean subjects. The inorganic phosphate concentration increased gradually (P less than 0.05) after glucose intake. The phosphocreatine/inorganic phosphate rate decreased (P less than 0.05) and the estimated ADP concentration increased. ATP and intracellular pH remained unchanged after the glucose administration. No changes were seen in the control experiments. The processes responsible for the decreased energy state of the skeletal muscle cell may be an obligatory conversion of glucose to glycogen. Also, facultative processes, such as sodium/potassium pumping and substrate cycles stimulated by the sympatho-adrenal system, may be partly responsible. PMID- 2596330 TI - Neural and biomechanical differences between men and young boys during a variety of motor tasks. AB - The adaptation in activation patterns of the ankle extensor muscles to different functional demands was studied in adult men (n = 10) and 9-year-old boys (n = 10). The relative magnitude of the activation of the slow soleus (SOL) and the relatively fast medial gastrocnemius (MG) muscle was measured during various postures and hopping tasks on a force plate. In addition, the myo-electric activity was quantified in three different phases of the stretch-shortening cycles during hopping. Major differences between boys and adults were observed in the postural tasks, where the boys appeared to utilize the MG to a relatively larger extent. During maximal height hopping there was a clearly larger potentiation of the MG activity in the adults, particularly in the eccentric phase. On the other hand, there were striking similarities between boys and adults with respect to the degree of pre-activation of both muscles during the different hopping regimes as well as potentiation of muscle activity during the concentric phase of maximal height hopping. Thus, some aspects of the selective neural control of the ankle extensor muscles appear to be manifested in pre pubertal boys. However, the data also indicate that other factors, such as utilization of stored elastic energy in the muscles and stretch reflex potentiation, will still continue to develop from the age of nine. PMID- 2596331 TI - Hypothalamic inhibition of duodenal alkaline secretion via a sympatho-adrenergic mechanism in the rat. AB - Experiments were performed on rats anaesthetized with chloralose. A duodenal segment was perfused with recirculating isotonic saline, and alkalinization of this perfusate (HCO3- secretion) was measured by continuous pH-stat titration. Stereotaxic electric unipolar stimulations were performed in the perifornical region of the hypothalamus. Stimulation points eliciting an increased arterial pressure were stimulated for a period of 15 min. Duodenal HCO3- secretion decreased in 19 out of 25 experiments and increased in four out of 25 experiments. Inhibitory responses to hypothalamic stimulation were blocked either by thoracic epidural anaesthesia or by the adrenolytic agent guanethidine, suggesting a spinal pathway to the duodenum, presumably in the thoracic splanchnic nerves, and involvement of adrenergic neurons. PMID- 2596332 TI - VIP antisera inhibit the relaxatory motor responses of the feline sphincter of Oddi and gall-bladder induced by VIP or vagal nerve stimulation. AB - Regional administration of VIP elicited a dose-dependent relaxation of the feline sphincter of Oddi and gall-bladder. Relaxatory motor responses of these regions at efferent electrical stimulation of the vagal nerves were unmasked after atropine (resistant to propranolol but sensitive to hexamethonium). These findings in combination with the presence of a rich VIP-ergic innervation, including intrinsic VIP neurons, have made VIP a tentative post-ganglionic non adrenergic, non-cholinergic neurotransmitter to these regions. The relaxatory motor responses elicited by VIP or vagal activation were selectively antagonized using regional administration of specific VIP antisera in support of this hypothesis. PMID- 2596333 TI - Suppression of small intestinal motility and morphine withdrawal diarrhoea by clonidine: peripheral site of action. AB - The effects of systemic administration of morphine (4.0 mg kg-1) and clonidine (2.5-10.0 micrograms kg-1), as well as the peripherally active alpha 2 adrenoceptor agonist oxymetazoline (2.8-11.2 micrograms kg-1), were studied on the migrating myo-electric complexes (MMCs) of the small intestine in conscious, naive rats. Furthermore, the effects of naloxone (1.0 mg kg-1) and the peripherally acting opioid antagonist, methylbromide naloxone (1.0-2.0 mg kg-1) were studied on the MMCs in morphine-dependent animals. Similar doses of clonidine or oxymetazoline inhibited the MMCs of the small intestine, which suggests a peripheral site of action of clonidine. Since naloxone (1.0 mg kg-1) did not antagonize the effect of clonidine, and yohimbine (1.0 mg kg-1) failed to antagonize the effect of morphine on the MMC, the inhibitory effects on intestinal motility of clonidine and morphine are mediated through different receptors. Morphine-dependent rats showed a prolonged interval between activity fronts and decreased propagation velocity of the activity fronts. Both naloxone (1.0 mg kg-1) and methylbromide naloxone (1.0-2.0 mg kg-1) induced intense spiking activity and profuse diarrhoea. Clonidine (5.0-10.0 micrograms kg-1) as well as oxymetazoline (5.6-11.2 micrograms kg-1) given prior to naloxone prevented the intense spiking as well as the concomitant diarrhoea. We conclude that the potent inhibition of small intestinal myoelectric activity by alpha 2 adrenoceptor agonists is mainly executed via peripheral mechanisms. This effect may contribute to their beneficial action in morphine withdrawal diarrhoea, and partly underlie a general antidiarrhoeal action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596334 TI - Potential-dependent potassium currents in the slowly adapting stretch receptor neuron of the crayfish. AB - The outward current in the stretch receptor neuron of the crayfish Pacifastacus leniusculus was analysed using a two-micropipette potential-clamp technique. The outward current was shown to be carried by K+. When the sodium-dependent inward current was blocked by tetrodotoxin a fast-activating potassium current was revealed, resembling the delayed rectifier. The time-course of activation (Tau n) was dependent on potential and had a mean value of I ms at potential steps of to mV. The activation followed a second-order process according to the Hodgkin Huxley model. The potential dependence of activation (n infinity) followed a sigmoid curve, n infinity = I/(I + exp [(E-En)/a]) with half-maximal activation potential En = -31 mV and a = -13 mV. When long pulses were applied, the potassium current showed marked inactivation with a fast time constant of 0.5 s that was potential independent and a slow component that was slightly potential dependent. The minimum value for the slow time constant was 4 s for steps to about 0 mV. The potential dependence of inactivation followed a sigmoid function k infinity = I/(I + exp [(E-Ek)/a]) with Ek = -39 mV and a = II mV. No transient potassium outward current (IA) was found in the crayfish stretch receptor neuron. In experiments on tail currents after depolarizing potential steps of different duration, it was found that the reversal potential changed in the positive direction when the duration of the pre-pulse increased. This could be due to K- accumulation in a space close to the neuronal membrane. The potassium current during depolarizing potential steps in the crayfish stretch receptor is similar to the delayed current found in other cells, for example the frog myelinated nerve, but different from many other invertebrate neurons. PMID- 2596336 TI - Calcium dependency of the post-stimulatory potentiation of the neurogenic response in small mesenteric arteries from the rat. AB - We have previously shown that the contraction of small mesenteric arteries in response to nerve stimulation is enhanced by preceding high-frequency stimulation. We have now investigated the calcium dependency of this post stimulatory potentiation. Small arteries (inner diameter 150-250 microns) from normotensive rats were dissected free from surrounding tissue, and segments were mounted in a myograph where the wall tension was measured at well-defined circumferences. Nerve stimulation was performed by field stimulation. A single stimulation of the nerve caused a contraction of 2.6 +/- 0.25% of maximal adrenergic response. After a high-frequency nerve stimulation with 16 Hz and 480 pulses the response to a single nerve stimulation was enhanced 6.6 +/- 1.3 times. The potentiation decayed with a time constant of 93.7 +/- 20.0 s. The amplitude of the post-stimulatory potentiation was dependent on the extracellular calcium concentration during the conditioning stimulation. In a solution containing 2.5 mM calcium the single twitch was enhanced 6.6 times while after exposure to reduced calcium (0.5 mM) it was only enhanced twice. The contraction caused by a short burst of high-frequency nerve stimulation (20 Hz and 10 pulses) was potentiated four times by a conditioning stimulation (16 Hz and 480 pulses), and this potentiation seemed to be independent of the extracellular calcium concentration during the conditioning stimulation. Thus the magnitude of the post stimulatory potentiation of single nerve stimulations is linearly related to the extracellular calcium concentration during the conditioning nerve stimulation. For the potentiation of the response to burst stimulation no relation was found between the potentiation and extracellular calcium. PMID- 2596335 TI - Characterization of the cardiovascular actions of endothelin in vivo: comparisons with neuropeptide Y and angiotensin II. AB - The cardiovascular actions of the endothelium-derived peptide endothelin were investigated and characterized in vivo. Intravenous bolus administration of endothelin (4-200 pmol kg-1) in the anaesthetized and chlorisondamine-pre-treated pig caused a dose-dependent increase in mean arterial blood pressure (MABP) with a threshold effect at 20 pmol kg-1 without affecting heart rate. Endothelin induced dose-dependent and long-lasting renal vasoconstriction. A slight effect was observed at 4 pmol kg-1 and the maximal response at 200 pmol kg-1 was a 648 +/- 210% increase in renal vascular resistance. The potency of endothelin in increasing MABP and renal vascular resistance was, on a molar basis, similar to that of angiotensin II and six times higher than that of neuropeptide Y. Administration of the calcium antagonist nifedipine (100 micrograms kg-1 i.v.) markedly inhibited the endothelin-induced increases in MABP and renal vascular resistance. The renal vasoconstrictor responses to angiotensin II and neuropeptide Y were similarily reduced by nifedipine (100 micrograms kg-1). A lower dose of nifedipine (10 micrograms kg-1) slightly attenuated the response to angiotensin II but not that to endothelin or neuropeptide Y. It is concluded that i.v. endothelin induces potent increases in systemic blood pressure and renal vasoconstriction in the pig. Nifedipine reduces the vasoconstrictor response to endothelin but not more than the responses to angiotensin II and neuropeptide Y. PMID- 2596337 TI - Perception of early parenting by patients diagnosed avoidant personality disorder: a test of the overprotection hypothesis. AB - The perceptions of their parents by patients diagnosed avoidant personality disorder (DSM-III) and matched normal subjects were compared. The overprotection hypothesis proposed by Parker was not found to predict the perceptions of patients diagnosed avoidant personality disorder. Social introversion in patients was found to be related to perceptions of their parents as shaming, guilt engendering and intolerant. PMID- 2596338 TI - Acute effect of electroconvulsive therapy on brain perfusion assessed by Tc99m hexamethylpropyleneamineoxim and single photon emission computed tomography. AB - Regional cerebral blood flow (rCBF) was measured in relative terms with Tc99m hexamethylpropyleneamineoxim and single photon emission computed tomography in 11 patients undergoing electroconvulsive therapy (ECT). The patients suffered from major depressive disorder (n = 8) or schizoaffective disorders (n = 3). rCBF was measured under general anesthesia 3 days prior to the ECT treatment and coinciding with the ECT stimulation. ECT caused a redistribution of the tracers uptake. The uptake became more pronounced in frontal parts of the brain and in the basal ganglia than in posterior parts of the cortex, and the thalamus. This selective effect of ECT on rCBF may be related to catecholaminergic projections to anterior parts of the brain. PMID- 2596339 TI - Cerebral perfusion inhomogeneities in schizophrenia demonstrated with single photon emission computed tomography and Tc99m-hexamethylpropyleneamineoxim. AB - Cerebral blood flow was measured in relative terms with Tc99m hexamethylpropyleneamineoxim (HMPAO) and single photon emission computed tomography (SPECT) in 28 female schizophrenic patients (20 acute and 8 chronic) classified according to DSM-III. Eleven normals served as controls. The acute patients were classified according to positive and negative symptoms. Patients with predominantly positive symptoms showed by and large normal and homogeneous cerebral isotope uptake. Those with negative symptoms, and the chronic patients, showed inhomogeneous tracer uptake with multiple regions of hypoperfusion in slices 4-6 cm above the orbitomeatal line. The findings support in principle the notion that schizophrenia with negative or chronic symptoms does not affect the whole brain homogeneously. Brain imaging with Tc99m-HMPAO and SPECT might be used to distinguish various types of schizophrenia. PMID- 2596340 TI - Diagnosis change, lithium use and admissions for mania in Edinburgh. AB - Admissions for mania have risen significantly in Edinburgh since 1970. Differencing was used to remove time trends; this showed that the rise was not accounted for by diagnosis change (from schizophrenia or personality disorder) or by lithium prescription. The contribution of non-specific factors such as admission policy and the experience of trainee psychiatrists deserves evaluation. If this rise continues there will be significant resource implications for the future. PMID- 2596341 TI - Patterns of psychiatric care in south Verona and Groningen. A case-register follow-up study. AB - The pattern of utilization of mental health services in south Verona (Italy) and in Groningen (the Netherlands) was studied. The local psychiatric case registers were used to select patients aged 15 years or more who had at least one contact in 1982 and no contacts in the previous 365 days. Each patient was followed for 36 months after the first contact in 1982. The 2 cohorts differed in size (373 in south Verona and 590 in Groningen), age, diagnosis and pattern of care, whereas the sex distribution was similar. The cohort in Groningen was characterized by a higher number of elderly people, suffering from organic psychoses. Drug dependence prevailed in south Verona, while alcohol dependence was predominant in Groningen. The pattern of care was classified according to 2 basic measures, the gross duration of care and the net duration of care. In south Verona single consulters were almost 3 times more common than in Groningen. In general, patients in Groningen tended to depend more on the mental health services. Linear regression analysis was used to determine the extent to which the pattern of care was predicted by the sociodemographical and clinical characteristics of the patients. Only the site where the contacts were made (south Verona or Groningen) and the diagnosis were significantly associated with the pattern of care. PMID- 2596342 TI - Depression among elderly people. A psychosocial study of urban and rural populations. AB - A total of 317 elderly subjects randomly selected among people living in the community in 1 urban and 2 rural areas were studied by means of a semistructured clinical interview, the Social Adjustment Scale, and the Beck Depression Inventory. An emerging trend was demonstrated towards a higher rate of prevalence of depression among females and urban residents. Widowhood, absence of a confidant, poor education and financial difficulties (only among urban elderly people) were significantly correlated with rates of depression. Physical impairments and diseases were also associated with depression, independently of whether subjects lived alone. The findings are discussed using a psychosocial frame of reference. PMID- 2596343 TI - Magnetic resonance imaging in Alzheimer's disease, multi-infarct dementia, alcoholic dementia and Korsakoff's psychosis. AB - Regional spin lattice relaxation times (T1) measured during nuclear magnetic resonance imaging of the brain were compared in patients with Alzheimer's disease, multi-infarct dementia, alcoholic dementia, Korsakoff's psychosis and control subjects. Regional differences were found between all patient groups compared with controls and within patient groups, with the exception of the comparison between Korsakoff's psychosis and alcoholic dementia. Correlations between regional T1 change and cognitive test scores were also found, with particular emphasis between visuospatial deficits and parietal T1. The possible role of T1 measures in the pathophysiology of these disorders is discussed. PMID- 2596344 TI - Mental disability among elderly men in Finland: prevalence, predictors and correlates. AB - Mental disability, variables associated with it and predictors of mental disability in late life were studied in 716 men from eastern and southwestern Finland in connection with the 25-year follow-up of the east-west study, which formed the Finnish part of the seven-countries study. The examinations were carried out in autumn 1984, when the men were 65-84 years of age. According to a 10-item mental status questionnaire, 95% of the men had normal mental capacities. There were no differences between the 2 areas. Old age, low educational level, low functional capacity, low body mass index, low serum cholesterol, low diastolic blood pressure, low alcohol or coffee consumption, low hemoglobin, low serum calcium, low serum triiodothyronine, high scores on the Zung Self-rating Depression Scale, and presence of transient ischemia or stroke were associated with mental disability in 1984. In the prospective analysis, low forced vital capacity, low forced expiratory volume in 0.75 s and high blood pressure in middle age predicted mental disability in old age. PMID- 2596345 TI - Does the act of migration provoke psychiatric breakdown? A study of Greek Cypriot immigrants. AB - This article describes a community psychiatric survey of a random sample (n = 291) of Greek Cypriot immigrants living in London. Over three quarters of the immigrants were first generation. Information from the subject and from hospital case records were used to date previous episodes of psychiatric disorder. Datable episodes had occurred in 52 subjects. There was no evidence that the risk of breakdown was increased in the immediate aftermath of immigration. For 34 subjects who experienced their first illness after migration, the mean interval was 15 years. In only 9% did breakdown occur within 2 years of migration. The age specific incidence of psychiatric disorder was the same as that seen in a native British sample. Although there were differences in the age of onset of first- and second-generation subjects, this was in the opposite direction to that expected if immigration appreciably provoked breakdown. PMID- 2596346 TI - Serum dopamine-beta-hydroxylase activity in clinical subtypes of depression. AB - Serum dopamine-beta-hydroxylase (DBH) activity was determined in male adult psychiatric patients (n = 280) and age-matched male healthy controls (n = 100). Patients included in the study had no history of previous or current exposure to psychoactive drugs and were diagnosed according to Research Diagnostic Criteria. A significant decrease in serum DBH activity was noted in patients with psychotic major depressive disorder (n = 50) as compared with controls. In acute schizophrenics (n = 100), nonpsychotic major depressives (n = 45) and patients with manic disorder (n = 85), mean DBH activity did not differ significantly from the control values. PMID- 2596347 TI - Smooth pursuit eye tracking and neuro-psychological performance in healthy volunteers. Exploring a possible genetic marker for vulnerability to schizophrenia. AB - Eye movement dysfunction (EMD) has been repeatedly found in schizophrenics and their first-degree relatives. In the present study, smooth pursuit eye tracking was measured in healthy subjects and related to performance on computerized neuropsychological tasks assumed to involve frontal or frontoparietal functions: monitoring perspective fluctuations (Necker cube), finger tapping, trail making, reaction time (RT) and a perceptual maze test. Poor trackers performed worse on tasks requiring parallel processing (trail making with letters and digits and RT with random auditory signals for response inhibition) and made more errors and cancellations on the mazes. Results are in line with our earlier EMD results on schizophrenics, showing poor performance on frontal tasks. However, their deficiency was more pervasive, whereas the present healthy EMD subjects only had difficulties with more complex tasks. The results are of interest in view of the recent evidence that EMD may be a genetic marker for vulnerability to schizophrenia. PMID- 2596348 TI - Platelet monoamine oxidase, plasma dopamine beta-hydroxylase activity, dementia and family history of alcoholism in chronic alcoholics. AB - The authors measured platelet monoamine oxidase (MAO) activity and plasma dopamine beta-hydroxylase activity in 36 male chronic alcoholics during a period of non-abstinence, and in 29 normal controls. The influence of family history, dementia, chronicity of drinking and liver injury on the enzyme activities was also examined by multiple regression analysis. Platelet MAO was significantly lower in the alcoholic group. Both enzyme activities were negatively related to the presence of dementia, while low MAO activity was associated with positive family history (parents, sibs) of alcoholism. PMID- 2596349 TI - A factor analytical study of the Comprehensive Psychopathological Rating Scale among patients with anxiety and depressive disorders. AB - A sample of 136 inpatients, meeting the DSM-III-R criteria for anxiety and/or unipolar depressive disorders, were rated on the 37 CPRS items designed for nonpsychotic disorders. By factor analysis we identified 2 indices: a 12-item depression index and a 7-item anxiety index. The indices proved to have good internal consistency and interrater reliability. They differentiated well between patients with anxiety and those with depressive disorders, and among subgroups of anxiety and depression. Our depression index may represent a slight improvement in specificity compared with previously suggested depression indices. Our main finding is the identification of an anxiety index with good psychometric properties. PMID- 2596350 TI - The heterogeneity of 3-methoxy-4-hydroxyphenylglycol levels among depressed patients. AB - A previous report by our group and results published by other research groups have indicated a dichotomy in MHPG levels in depressed patients. This study attempted to characterize phenomena associated with this dichotomy in plasma MHPG levels. First, we have noted, at least in female patients, that homogeneity of MHPG levels, as tested by fitting with a normal curve, can be ruled out. In contrast, in the total population, a dichotomy was less evident in this study; the 2 subgroups, high and low levels of MHPG, partially overlap, and this results in a gaussian distribution. However, based on the hypothesis of a bimodal distribution, as shown by others and not excluded here, it was possible to find some factors associated with heterogeneity. Thus, polarity of depression, sex and age of the patients, age of disease onset and depression score affect MHPG levels. On the other hand, other elements suspected to modify MHPG values, such as the different lengths of the washout period (minimum 10 days), or some medication (chloralhydrate or levomepromazine) required during the washout period, did not show any effect. The aim of this study was to better characterize this peripheral index for its possible use in clinical application. PMID- 2596351 TI - Alcohol withdrawal and mood. AB - The usefulness of a self-report technique for description of mood was tested at various stages of alcohol withdrawal. The Mood Adjective Check List (MACL), consisting of 71 mood-associated adjectives and measuring 6 bipolar aspects of mood, was used. Three groups of alcohol-dependent patients (DSM-III-R) reported on their momentary mood states twice a day, respectively, during early withdrawal (n = 78), during late withdrawal (n = 13), and after full remission (n = 12). Significant improvement was found in all 6 mood dimensions during early withdrawal. Improvement in 3 basic mood dimensions was also found during late withdrawal, thus indicating a prolonged time of recovery. The reports given by patients in full remission showed no changes in mood over time. Relative to norm group values, significant differences were found in 4 of the 6 mood dimensions for patients in very early withdrawal. The present study shows that mood changes attributable to after-effects of alcohol intake can be assessed and described during various stages of withdrawal. PMID- 2596352 TI - [Multivariate statistics in urologic research (III). Survival analysis]. PMID- 2596353 TI - [Antibiotic prophylaxis in endoscopic urologic surgery]. AB - Recent studies have shown the value of antibiotic prophylaxis with short therapy periods in patients submitted to transurethral surgery. We have carried out a prospective study on 46 patients, all with negative urine cultures prior to the intervention, divided into two groups: one control and the other with short cefuroxime prophylaxis. With the latter a reduction in post-operative infectious complications was obtained, and specifically of postoperative bacteriuria, from a 70% in the control group to al 13% in the prophylaxis group. The results are statistically significant. PMID- 2596354 TI - [Renal outcome in myelodysplastic patients with untreated, risky vesico-sphincter dysfunction]. AB - Poor vesical accommodation with competent sphincter system and bladder-sphincter dyssynergy are major risk factors for renal function in patients with myelomeningocele. We present four cases with these urodynamic features and we analyse renal variation with time in relation to these, pointing out the poor evolution. We emphasize the need for urodynamic study with simultaneous radiology and early treatment when these risk factors exist. PMID- 2596356 TI - [Hemospermia: clinical study]. AB - We present a clinical study of 29 patients with macroscopic hemospermia. The associated symptoms prevailed over monosymptomatic presentation. Urethral prostate-vesicular inflammation was the most common etiology (55%). We single out the presence of a seminal vesicle cyst, two malignant urogenital tumours and one patient with presentation of the post-radiotherapy symptom. In 24% of the cases the cause was unknown. Diagnosis was done preferably by means of case clinic and sexual history, physical exploration, prostate/seminal vesicle echography and bacteriological-cytological study of the urine fraction plus semen. We carried out other diagnostic explorations on a selective basis. We consider hemospermia to be a benign symptom, although its presence requires the carrying out of a methodical series of explorations to rule out other pathologies of very diverse condition worthy to being taken into account. PMID- 2596355 TI - [Fistulization in xanthogranulomatous pyelonephritis. Presentation of 6 clinical cases and review of the literature]. AB - Fistulization is an uncommon complication in Xanthogranulomatous Pyelonephritis, but harmful for the adjacent organs. Owing to their rare localization we present 6 cases with scrotal skin, bronchi, colon and spleen fistulization. PMID- 2596357 TI - [Calcification and contamination as complications in the use of double-J catheters: incidence and correlation]. AB - We present a series of cases of complex renal lithiasis, in which we carried out temporary internal urinary bypassing, prior to extracorporeal lithotripsy, by means of the retrograde insertion of a double-J urethral catheter, studying the time of stay, the presence or not of contamination in the catheter and its relationship with the calcifications found in them. We also carried out a metabolic-functional study of each patient, determining the urinary pH and the serum and urinary calcium, phosphorous and uric acid concentrations, and observing their possible influence on the above-mentioned complications. Of the 25 catheters studied, we observed calcification in 11 cases (44%). In these we observed urealytic germs (Proteus and Pseudomonas), without finding modifications of urinary pH. We observed no relationship between the calcium deposits and serum and urinary calcium, phosphorous and uric acid concentration. PMID- 2596359 TI - [Necrotizing perineal phlegmon (Fournier's gangrene)]. AB - The scrotal and perineal necrosis process, known as Fournier's gangrene, constitutes a characteristic clinical pattern of fulminating course and high mortality. In this series, we analyse 22 patients bearers of this condition treated in our service over the last 10 years. Their average age was 60.6. A factor unleashing the infectious process could be shown in 14 patients (63.6%), chiefly urogenital pathology. Six patients were diabetic (27.3%). The treatment favoured by the authors contemplates early surgical intervention with limited debridement, ample drainage, wide spectrum antibiotics and cystostomy in appropriate cases. With this schema the mortality of the series was only 9.1% (2 patients). This entity represents a real urological emergency. Its early identification and prompt appropriate treatment are key elements for bringing down the high mortality. PMID- 2596358 TI - [Urologic pathology in patients positive for anti-HIV antibodies]. AB - Between May 1987 and November 1988 we performed the human immunodeficiency virus (HIV) antibody serological test on 586 patients of the Urology and Nephrology Services, and it was positive in 14 cases. Of these, 6 came on account of urological pathology: bilateral cryptorchidism, giant condylomata acuminata, acute pyelonephritis and three acute orchi-epididymitis. All the patients were intravenous drug addicts. Although it is a case of common urological pathology and not secondary to the acquired immunodeficiency syndrome, it takes on a different significance as regards the risk population in which it occurs. PMID- 2596360 TI - [Acute renal insufficiency secondary to ureteral obstruction]. AB - Acute renal insufficiency due to ureteral obstruction is relatively uncommon and gives rise to difficulties of diagnosis and treatment. The series presented here analyzes these aspects in 24 patients who had 27 episodes of proven anuria due to ureteral obstruction. Their average age was 62. Six patients had only one kidney (25%). The most common etiology was cancer (two thirds of the cases), mainly of genitourinary origin (10/16). Calcium or uric acid urethral lithiasis was the main cause of obstruction in the benign group. Treatment corresponded to a wide range of obstruction removal procedures depending on the etiology, but in the secondary to cancer it was very aggressive and the most used was nephrostomy. The decision to perform any treatment of obstructive anuria in patients with cancer should take into account a variety of important aspects amongst which prevail the prognosis of the basal illness, the handling of cancerous pain, the complications and mortality associated with the procedure and the patient's prospects. PMID- 2596362 TI - [Giant urethral lithiasis]. AB - We present a case of giant urethral lithiasis, housed in the penile urethra. Owing to the scant incidence of this pathology and its rarity, as well as the small number of bibliographic references found, we believe it of interest to offer this fresh case. PMID- 2596361 TI - [Adenomatoid tumor of the albuginea testis]. AB - We present a rare case of adenomatoid tumour situated in the testicular albuginea. We comment on its treatment, which we are of the opinion should be conservative. PMID- 2596363 TI - Children's understanding of mental phenomena. PMID- 2596364 TI - Uterine perforation and use of the Multiload IUD. AB - The English language literature on IUDs was reviewed to evaluate the uterine perforation rate associated with use of the Multiload. No reports of cervical perforation were found, and the uterine perforation rate was 0.12/1000 insertions compared to a rate of 0.68/1000 insertions for other copper-bearing IUDs. This lower rate may reflect an under-reporting of uterine perforations in the medical literature, or may represent a truly lower perforation rate due to factors related to the Multiload design and/or its insertion technique. PMID- 2596365 TI - A study comparing a gestoden triphasic formulation with a fixed combination OC. AB - Metabolic parameters were studied in 30 patients over 12 treatment cycles in a double-blind randomized comparative trial of the new progestogen gestoden in a triphasic formulation against a fixed dose combination pill containing desogrestrel, in Bandung, Indonesia. The results of this laboratory experience affirm findings in similar previous metabolic studies that: (1) the changes induced by modern low-dose pills are clinically and statistically insignificant; (2) throughout the treatment cycles, the values of the various laboratory tests remain well within the normal range; and (3) the favorable balance between coagulation and fibrinolysis is maintained. Results of lipoprotein, coagulation, fibrinolytic and liver function tests in 27 patients are presented. Gestoden's pharmacologic profile and the worldwide clinical experience with the triphasic gestoden formulation in 4285 women are discussed. PMID- 2596366 TI - The forehead lift: techniques to avoid complications and produce optimal results. AB - This discussion of forehead lifting, based on modifications of Vinas, Caviglia, and Cortinas, shares the authors' methods of patient evaluation, diagnostic details, architectural planning, and surgical concepts for forehead rhytidectomy along with correction of malpositioned and ptosis of the eyebrows and also glabellar frown problems. In addition, the nasal deformities associated with the sagging of the skin and subcutaneous tissue onto the upper fourth of the nose may make the nose look too short for a pleasing balance of the face and the upper fourth may appear disagreeably wide. A contribution to this excessive width is made by a sometimes thick and wide procerus muscle along with bilateral thick depressor supercilii muscles. When this nasal deformity is corrected, glabellar frown problems are also corrected. Attention to the details of the above mentioned factors results in very long-lasting, sometimes permanent, and almost complication-free results that please the surgeon and the patient. Complications such as adherence of the dermis to the underlying pericranium, lack of motion in a portion of or the entire forehead, hyperactivity around areas of immobility, muscle irregularities, and also surgically produced depressions which require grafting, skin sloughing, permanent nerve injury, persistent sensory nerve loss, and short-term improvement have been avoided by paying attention to diagnosis, surgical planning, and technique, and postoperative care. Most patients can return to work in four or five days with minimal discoloration and swelling if they have not had aspirin or vitamin E one month before surgery, and there is hemostasis and the use of drains when indicated. Minimizing detection of the surgical incisions is accomplished by detailed preoperative planning of their location, architectural design development and drawing at the time of surgery, special surgical techniques, and excision of the skin or scalp. For patients with male pattern baldness use of specially designed V-Y advancement flaps with the browlift procedure improve the appearance of the hair's thickness and distribution. PMID- 2596367 TI - The rationalization of liposuction: toward a safer and more accurate technique. AB - Liposuction, like all surgical procedures, is subject to complications and unfavorable results. Since it is a closed procedure and departs from the usual concept of surgery, its practice is, to a large extent, based on subjective intraoperative estimation. Therefore, it is liable to errors that might have serious local and systemic consequences. In an attempt to improve the technique, the authors have designed new instruments: the "tunnel tracer" and the "guided cannulae." They provide the basis for systematizing the procedure and applying it in a more rational manner. With these instruments and the methodology described in this article, over the last three years we have obtained very satisfactory results and notable reduced morbidity. The advantages are less trauma, less risk, less hemorrhage, less effort for the surgeon, and greater precision. PMID- 2596368 TI - Lower lid "tarsal fixation" blepharoplasty: a personal technique. AB - The majority of patients seeking lower-lid blepharoplasty find that a muscle roll under their lower-lid ciliary margin is a desired postoperative feature. Very few prefer a flat postoperative lower lid. In addition to the cosmetic advantage obtained by more closely simulating a youthful lower eyelid, preservation of the pretarsal portion of the orbicularis oculi muscle also has a physiologic value in maintaining lower eyelid tone and support. A method to create this fold, which included placement of tarsal fixation sutures, has been previously described. It was accompanied by prolonged postoperative swelling. In hands other than masterful surgeons, it often resulted in irregular shape and asymmetry. Perhaps this is why the technique never became very popular. The technique described here consists of overlapping two layers of orbicularis oculi muscle over the lower lid tarsal plate. The method is simple, quick, requires no additional sutures, and does not complicate or prolong the postoperative course. The result is that of a soft, even, and natural appearing lower eyelid roll and lower eyelid. PMID- 2596369 TI - Cranial nasal bone grafts. AB - Reconstitution of the nasal scaffolding with maintenance of soft tissue proportions either following severe facial trauma or as a sequela to aesthetic rhinoplasty misadventures frequently is best achieved using the stability afforded by bone grafts. Split cranial bone grafts offer many advantages and may be the donor site of choice, and may even allow such surgery to be performed on an outpatient basis in some cases. The use of miniplate or screw osteosynthesis, now commonly accepted as a superior technique in craniomaxillofacial procedures, may simplify fixation of these calvarial nasal bone grafts with an apparent decrease in the risk of resorption. PMID- 2596370 TI - The effect of disodium 4-chloro-2-iminodibenzoate (CCA) on IgE levels and anaphylactic shock. AB - The effect of disodium 4-chloro-2,2-iminodibenzoate (CCA) on IgE antibody response was examined in C3H/A and (BALB/c x C57BL/6J) F1 hybrid mice immunized with low doses of ovalbumin (OA) adsorbed on aluminium hydroxide gel. CCA administered orally at the doses of 5 and 50 mg/kg/day reduced IgE antibody production in these mice as determined by PCA test. High doses of CCA (100 mg/kg/day) given from day 7 before immunization of C57BL mice and during 1 week after immunization of mice with OA and Bordetella Pertussis Vaccine reduced the mortality of these mice subjected to anaphylactic shock on day 7 of immunization. CCA treatment was ineffective in anaphylactic shock of C57BL mice immunized with very high dose of OA, known to elicit little or no IgE antibody production but high IgG antibody response. The treatment of OA-immunized Guinea pigs with one oral dose of CCA (100 mg/kg) did not reduce mortality in protracted anaphylactic shock. Our results demonstrate that CCA inhibits IgE production as well as IgE mediated hypersensitivity reactions in mice. PMID- 2596371 TI - Effect of ketotifen on the distribution and degranulation of uterine eosinophils in estrogen-treated rats. AB - Eosinophil leukocytes migrate from the blood to the uterus under estrogen stimulation, redistribute through uterine extravascular compartment, degranulate in the organ, and release agents that are involved in several parameters of estrogen action. Agents that induce blood eosinopenia, block their migration to the uterus, interfere with their redistribution within the organ or modify their degranulation, selectively interfere with eosinophil-mediated responses to estrogen. The present study investigated whether ketotifen, an antiallergic agent that inhibits allergen-induced eosinophil degranulation, interferes with estrogen induced eosinophil migration to the uterus and their subsequent degranulation. Ketotifen does not interfere with estrogen-induced eosinophil accumulation in the uterus, but decreases the proportion of eosinophils located in endometrium and inhibits their degranulation. These results suggest that neither histamine, calcium or slow reacting substance of anaphilaxis are involved in eosinophil migration to the uterus. The inhibition by ketotifen of eosinophil degranulation may diminish eosinophil migration through extravascular compartment via a decrease in the release from degranulating eosinophils of enzymes required for this migration. It is possible that the inhibition by ketotifen of both, eosinophil degranulation and eosinophil motility through uterine extravascular compartment, interfere with eosinophil-mediated responses to estrogen or with other functions of these cells. PMID- 2596372 TI - The inhibition of 5-lipoxygenase by RG 6866. AB - The generation of leukotrienes C4, D4 and E4 from arachidonic acid is dependent upon the activity of 5-lipoxygenase (5-LOX). The effects of RG 6866 (N-methyl-4 benzyloxyphenylacetohydroxamic acid) on the activity of guinea pig 5-LOX in vitro and in vivo were determined in the present study. The generation of 5-hydroxy 6,8,11,14-eicosatetraenoic acid (5-HETE) from arachidonic acid by isolated guinea pig peritoneal polymorphonuclear (PMN) cells was inhibited by incubation with RG 6866 (IC50 = 0.20 microM). A similar effect (IC50 = 0.23 microM) was observed when 5-HETE production was measured in a supernatant fraction from PMNs. Additionally, the compound did not inhibit 3H-LTD4 binding to guinea pig membranes. In actively sensitized guinea pigs pretreated with indomethacin, propranolol and pyrilamine, RG 6866 inhibited antigen-induced systemic anaphylaxis and LTD4-dependent bronchoconstriction in a dose-dependent manner following oral administration. In the pulmonary anaphylaxis model, significant (p less than 0.05) inhibition of the mortality was observed within 30 min and maintained through four hours after treatment with RG 6866 (50 mg/kg i.g.). Finally, orally administered RG 6866 inhibited the formation of LTC4 in these animals with an ED50 = 24.0 mg/kg. These findings indicate that RG 6866 is an inhibitor of 5-LOX both in vitro and in vivo. PMID- 2596373 TI - Nutrient solution may alter the effect of the H2 blocker famotidine in the guinea pig papillary muscle. AB - The effect of different nutrient fluids (Ringer or Krebs) on the antagonism induced by the new H2 blocker famotidine against histamine was studied in the guinea pig isolated papillary muscle. The response to histamine was the same in Ringer and in Krebs solutions, as for threshold concentration and maximum response, conversely the antagonism induced by famotidine was found to be dependent on the nutrient fluid employed. It was competitive for low concentrations of the drug in both fluids, whereas the unsurmountable antagonism caused by higher concentrations in Ringer was reversed into a classical competitive one in Krebs. The potency of famotidine did not vary (pA2 values = 7.86 and 8.09 in Ringer and Krebs, respectively). The addition of PO4 or Mg++ to Ringer or the pH adjustment, in order to minimize the differences in the ionic content, did not modify the results obtained. The above data suggest that the antagonism by high concentrations of famotidine against histamine may be competitive or unsurmountable according to the nutrient fluid employed and stressed the importance of the ionic environment in the drug-receptor interaction. PMID- 2596374 TI - H1-receptor reserves in guinea-pig left atria, trachea and pig coronary artery as identified by phenoxybenzamine. AB - H1-receptor reserves in guinea-pig left atria, trachea and pig coronary arteries were calculated by the use of phenoxybenzamine (Pba), a beta-haloalkylamine that irreversibly blocks the H1-receptor response to histamine or 2-(2-pyridyl) ethylamine (PEA). Equieffective concentrations of the H1-agonist in the absence (A) and presence (A') of Pba were evaluated from concentration-response curves. By plotting the reciprocal values 1/A versus 1/A' the amount of H1-receptors not occupied by the agonist was calculated. The size of the H1-receptor reserve could be estimated by comparison of the receptor occupation with the corresponding effect. Furthermore, the dissociation constants for histamine, PEA, Pba and the pD'2-values for Pba were determined for the different tissues. 5% and 6% H1 receptor occupation is necessary to achieve a half maximal contraction of the trachea with the agonists histamine and PEA, respectively. Only 0.5% H1-receptor occupation is needed for the half maximal positive inotropic effect of histamine in left atria, while 5.5% of the H1-receptors have to be occupied using PEA as an agonist in this tissue. In the coronary artery of the pig 50% of the maximal contraction can be achieved by stimulation of 15.1% of the H1-receptors with histamine. PMID- 2596376 TI - Leucocyte-endothelial cell interaction. Inaugural meeting of the British Inflammation Research Association (BIRAs) 7th June, 1988. PMID- 2596375 TI - Vidian nerve resection, histamine turnover and mucosal mast cell function in patients with chronic hypertrophic non-allergic rhinitis. AB - Parasympathetic innervation of the respiratory tract of nasal mucosa plays an important role in the pathogenesis of chronic hypertrophic non-allergic rhinitis (C.H.N.A.R.), the vidian nerve providing the main parasympathetic nerve supply to respiratory mucosa. The present study investigates the effect of vidian nerve resection in 22 patient with intractable C.H.N.A.R. on histamine content and formation and on the number of mast cells and their degranulation in the respiratory tract. Samples were taken from respiratory mucosa for histamine and histidine-decarboxylase assay, and for microscopic observations for mast cell density and degranulation index, before and 12-24 months after vidian nerve resection. Neurectomy of the vidian nerve completely cured the clinical symptomatology, evaluated by rhinoreomanometry, and also significantly decreased both the high histamine levels and histidine-decarboxylase activity in patients with C.H.N.A.R. The density and degranulation index of mast cells were also significantly lower after surgery. These data suggest a relationship between cholinergic activity and the secretory response of mast cells and indicates a correlation between the parasympathetic nerve supply and chronic hyperthrophic non-allergic rhinitis. The significant reduction in mast cell density, histamine levels and histidine-decarboxylase activity also lends support to the hypothesis that the parasympathetic nerve supply plays a role in the regulation of mast cell histamine. PMID- 2596377 TI - Cathepsin B and D activity in alveolar macrophages from rats with pulmonary granulomatous inflammation or acute lung injury. AB - Cathepsin B and D activity was determined using specific synthetic substrates in alveolar macrophages (AMs) obtained from Sprague-Dawley rats with experimentally induced pulmonary granulomatous inflammation. Increased cathepsin B activity was found 4 days after intravenous injection of complete Freund's adjuvant (CFA), but not after injection of live bacillus Calmette-Guerin organisms (BCG), indicating that the enzyme response was unrelated to the subsequent development of granulomatous inflammation. Findings of comparable increases in enzyme activity following injection of mineral oil (MO) indicate that the response to CFA was due to the oil component. Significantly, oleic acid (OA), a natural fatty acid, did not stimulate enzyme activity although the agent, like MO, caused acute lung injury as assessed by 125I albumin uptake. At 7 and 28 days following injection of CFA, cathepsin B levels in AMs were the same as those in animals given normal saline (NS), although bronchoalveolar lavage (BAL) samples still contained increased numbers of AMs, and cells obtained at 28 days phagocytosed more polystyrene microspheres. Cathepsin D activity did not increase 4 days after injection of CFA or BCG + CFA; at 28 days following injection of BCG + CFA activity was significantly decreased as compared to animals given NS. The data reveal a differential response of two lysosomal enzymes during the early phases of granulomatous inflammation. PMID- 2596378 TI - Dietary effects of pristane on rat lymphoid tissues. AB - Studies were conducted to assess the normal tissue-associated levels of pristane (2,6,10,14,-tetramethylpentadecane) in Copenhagen rats during ontogeny and adult life and to address whether or not dietary pristane can be adsorbed from the gut and disseminated throughout the body. During the course of this study the possible effects of dietary pristane on chromatin conformation of lymphoid cells were also examined by flow cytometry. The data indicated that 1) pristane crossed the placenta and accumulated in fetal tissues, 2) neonates were exposed to pristane via the colostrum, 3) there were significant increases in the amount of tissue-associated pristane in young adults and subsequent redistribution of the pristane to the muscle and adipose tissues in older rats and 4) after dietary exposure, significantly elevated levels of pristane were associated with the tissues and concomitant changes in chromatin conformation were observed. Collectively, these results suggest that pristane was adsorbed from dietary sources, disseminated to the tissues and exerted a transient, yet marked effect on chromatin of lymphoid cells in rats. PMID- 2596379 TI - Improved method to estimate oxygen consumption, diffusing capacity and blood flow of synovial membrane. AB - The joint cartilage is depending on the oxygen diffusing from the capillaries of the synovial membrane through the synovial tissue and synovial fluid. In the present study we describe a new method to calculate the diffusing capacity (DO2), oxygen consumption (VO2) and blood flow of the synovial membrane. The principle of the method is to perfuse the joint cavity with two saline solutions, one with high and one with low oxygen and nitrogen partial pressures and to measure the oxygen and nitrogen partial pressures in the perfusate flowing out of the joint. Using a model of gas exchange between the joint and the membrane a set of equations was derived expressing the relationship between the blood flow, diffusing capacity and oxygen consumption and the oxygen and nitrogen flowing to and from the joint in the two different perfusion situations. In 12 rabbit knee joints we found a blood flow of 0.388 ml/min (SEM 0.027), VO2 of 0.495 microliters/min (SEM 0.196) and DO2 of 0.024 microliter/min/Torr SEM 0.003 (mean). PMID- 2596380 TI - Oxygen consumption, diffusing capacity and blood flow of the synovial membrane in osteoarthritic rabbit knee joints. AB - In osteoarthritis the changes of the synovial membrane may seriously alter the oxygen transfer characteristics from the capillaries of the membrane to the synovial fluid and hence impede or deprive the joint cartilage of its sole source of oxygen. In the present study we have estimated the blood flow (Q), diffusing capacity (DO2) and oxygen consumption (VO2) of the synovial membrane in the chronic non effusive stage of experimental osteoarthritis. In 14 osteoarthritic knee joints we found a statistically significant increase in oxygen consumption, compared to previously reported results from normal joints, whereas the diffusing capacity and the blood flow were unchanged. The implication of this is that the partial pressure difference required to overcome the increased oxygen consumption was increased with a factor 4.3 and that the oxygenation of the joint cartilage was reduced with approx. 30 Torr. PMID- 2596381 TI - Drug enrichment of commercial poultry feeds and human health in the tropical developing countries. AB - Eighty per cent of Enterobacteriaceae isolates from battery poultry exhibited drug resistance in a survey among university and commercial poultry flocks. These birds, being a source of human food, may serve as an important reservoir for human pathogenic drug-resistant enteric organisms. Feeds used on University and Commercial poultry farms were found to be inhibitory to standard test organisms- Oxford strain of Staphylococcus aureus and Escherichia coli K 12 J5 NA+ Lac-. Feed additives, which purportedly were mineral and vitamin supplements, were found to be highly laden with antibacterials, a quantitative estimation of which revealed that one of them, termed A & D Crumbles contained as much as 3000 (three thousand) micrograms of antibiotic per g, while another feed additive known as ADVIT contained 130 micrograms of antibiotic per g of the feed supplement. These are routinely added to poultry feeds, a practice which may easily lead to development of drug resistance among enteric pathogens that may, in turn, reach humans and complicate therapy of human bacterial infections. This may be of a considerable public health significance. PMID- 2596382 TI - Sex determination of bovine embryos based on embryonic cleavage rates. AB - Bovine embryos (n = 64) collected at day-6 from 10 superovulated and inseminated donors were evaluated upon recovery and again after incubation for approx. 12 hrs. According to cleavage rate they could be divided into a fast, an intermediate and a slow developing group, respectively. This grouping was correlated to embryonic sex determined by karyotyping (n = 29). From the fast developing group we found 7 males and 2 females (male ratios 78%), from the intermediate group 3 males and 8 females (male ratio 27%) and from the slow group 1 male and 8 females (male ratio 11%). From this preliminary study it is concluded that the rate of embryonic development may be used as a sex discriminator. PMID- 2596383 TI - Sex determination of bovine embryos using H-Y antibodies. AB - 6 days old bovine embryos (n = 126) were obtained from 8 superovulated cows or heifers by flushing the uteri and oviducts either non-surgically or after slaughter. Part of the embryos (n = 72) (morula stages) were placed in Ham's F-10 or PBS supplemented with 10% fetal calf serum (FCS) diluted 1:1 with supernatant from the H-Y antibody producing clone and cultured at 38 degrees C, in 5% CO2/95% air and 100% humidity. Control embryos (n = 54) were cultured in H-Y antibody free medium. After culture the embryos could be separated into a blastocyst--and a morula group. A subsequent colchemid and hypotonic treatment and fixation and Giemsa staining allowed a precise karyotyping, and thus sex determination for 36 H-Y antibody treated embryos and 22 control embryos. The limiting factor for proper karyotyping was lack of metaphases, incomplete methaphases or poor preparation. Among the H-Y antibody treated embryos we found 7 males and 15 females in the blastocyst and 14 males and 0 females in the morula group. A statistical analysis of these proportions led to the conclusion that the H-Y antibody had a significant influence on the sex ratio. PMID- 2596384 TI - Studies on microaerophilic cocci (Stuart-Schwan cocci) isolated from summer mastitis and other pyogenic infections of cattle. AB - Forty-nine strains of microaerophilic gram-positive cocci (Stuart-Schwan cocci) isolated from summer mastitis, "pyogenes"-mastitis, other pyogenic conditions of Danish cattle and swine, and from the sheep headfly Hydrotaea irritans were biochemically characterized with the API 50 CH and API ZYM test kit systems, and screened for production of a variety of extracellular enzymes by agar plate methods. For comparison 4 strains isolated from Swedish cases of heifer and dry cow mastitis were included in the study. Similarity calculations indicated a high degree of homogeneity within the strains studied (similarity level 92%; group mean similarity 87%). The strains probably represent one species, although the taxonomic position of the organism remains unclear. The biochemical feature of the strains studied were very similar for strains isolated from cases of summer mastitis and strains from other sources of origin. It is suggested that the Stuart-Schwan coccus occurs as a natural cohabitant to Actinomyces pyogenes, Peptostreptococcus indolicus and the anaerobic organism characteristic of the bacterial complex isolated from summer mastitis and similar pyogenic conditions in ruminants and swine. PMID- 2596385 TI - Thyroxine in blood plasma related to plasma levels of acetoacetate and glucose in ketotic and healthy cows. AB - Plasma samples were taken before morning feeding twice weekly for the first 3 months post partum from 28 individually fed cows, of which 8 developed clinical ketosis. Feed rations consisted of grass silage ad libitum and concentrates. The high incidence of ketosis may be accounted for mainly by substandard amounts of feed energy, and by variations in the quality of the grass silage. The following sources of post-partum thyroxine variation were found to be statistically significant (p less than 0.001): The individual cow, the individual pre-calving thyroxine level, metabolic status estimated by plasma levels of acetoacetate or glucose, and elapsed time from partus. The post-partum decrease in thyroxine was greater in cows which developed ketosis (55%) than at the corresponding stage of lactation in those which remained moderately ketonaemic (33%). Extensive overlapping of ranges nevertheless indicates that the apparent hypothyroidism of ketosis is of limited importance for the etiology of the disease. Susceptibility to ketosis was not related to the thyroxine levels observed before partus or after recovery from the disease, in the third month of lactation. Evidence was obtained of a common glucose threshold of about 3.6 mmol/l, below which decreasing sugar levels were accompanied by progressive increments in acetoacetate and decreases in thyroxine. Above the threshold level, the average level of the hormone increased from the first to the third month of lactation in spite of a poor correlation to glucose. PMID- 2596386 TI - Variations in parameters of liver function and plasma progesterone related to underfeeding and ketosis in a dairy herd. AB - Twenty-eight Norwegian Red Cattle dairy cows were fed silage ad libitum and restricted amounts of concentrates. Blood samples were collected before morning feeding, once or twice weekly, from 2 weeks before to 12 weeks after calving. Parameters of liver function, carbohydrate status and fertility were recorded in order to assess their interrelationships. Eight cows were treated for clinical ketosis. Four of these had to be treated 2 or 3 times. Aspartate aminotransferase and bilirubin showed the highest within-animal coefficients of correlation with acetoacetate. Analysis of variance revealed a significant effect of carbohydrate status (indicated by plasma acetoacetate levels) on the levels of aspartate aminotransferase, glutamate dehydrogenase and sorbitol dehydrogenase, though only a small part of the total variation was explained by this factor. The estimated volume density of liver fat in the 4th week of lactation averaged 6.0 +/- 6.4% (+/- SD) ranging from 0.1-25.1%. Liver fat content at this stage of lactation was not significantly correlated with other indicators of liver function or carbohydrate status. Cows treated for clinical ketosis had significantly lower plasma progesterone values at the time of first ketosis treatment than untreated multiparous cows. The frequency of high progesterone values (greater than 3 ng/ml) being significantly lower in treated than in untreated cows during the period from 3-5 weeks post partum, though not at later stages. In conclusion, the results revealed a significant relationship between carbohydrate status and liver function, and also between clinical ketosis and luteal function. PMID- 2596387 TI - Levels of milk urea, plasma constituents and rumen liquid ammonia in relation to the feeding of dairy cows during early lactation. AB - The study was undertaken to establish the relationships between milk and plasma urea levels and protein supply, using traditional and new measures of feed protein value. Samples of milk and plasma were taken before morning feeding twice weekly for the first 3 months post partum from 21 multiparous cows and 7 heifers. Samples of rumen fluid were collected every second week. The cows were distributed into 4 different feeding groups. Feeding regimens were factorial with respect to protein content of the concentrates (i.e. Low protein (Lp): 12.5% digestible crude protein (DCP) vs. High protein (Hp): 17.5% DCP) and concentrate allowances (i.e. Low energy (Le): substandard vs. High energy (He): standard). Silage was offered ad libitum. The within-animal coefficients of correlation between milk and plasma urea levels, and between milk urea levels and the levels of ammonia in the rumen fluid wer r = 0.88 (p less than 0.001) and r = 0.75 (p less than 0.001), respectively. Analysis of variance showed the following sources of urea variation to be significant: Protein balance in the rumen (PBV), intake of DCP, intake of amino acids absorbed in the intestine (AAT), intake of fattening feed units, and the individual animal factor. A similar tendency was found for the variation of ammonia in rumen fluid. The coefficients of determination (R2 model) were not increased by introducing protein balance (BADCP), the amount of PBV and AAT in the dry matter ingested, or the protein/energy ratio as alternative parameters of protein intake in the models. The levels of protein or energy intake did not significantly influence the levels of plasma albumin. The correlations between urea levels and other plasma indicators of metabolic status and liver function were generally low. PMID- 2596389 TI - Diurnal and individual variations in bile acids in the plasma of normal dairy cows. AB - Blood samples were collected every 2 h during a 24 h period from 6 cows of one herd and 10 cows of another herd. In a third herd 9 cows were sampled every 2 h from 6 a.m. to 8 p.m. Concentrations of total bile acids, acetoacetate, glucose and free fatty acids were determined in blood plasma. A marked difference in individual bile acid concentrations and patterns of diurnal variation was found. For most cows the highest bile acid values were observed between 2 and 6 a.m. (overall mean (+/- SD) at 6 a.m.: 104 +/- 84 mumol/l, range: 20-307 mumol/l). Fourteen cows with a bile acid value greater than 90 mumol/l at 6 a.m. ("high BA") were characterized as a group by showing a pronounced decrease in the mean bile acid concentration after morning feeding. In the group of 11 cows with a 6 a.m. bile acid value less than 90 mumol/l ("low BA") the time of day did not contribute significantly to the bile acid variation. For the "high BA" group a nearly synchronous variation between the mean values of the 3 feeding dependent parameters (acetoacetate, glucose and free fatty acids) and the mean values of bile acids was found. The within animal coefficients of correlation between bile acids and the feeding dependent parameters were significantly higher in the "high BA" group than in the "low BA" group. No direct connection was found between bile acid levels and the quantity of concentrates fed or the individual milk yield. PMID- 2596388 TI - Immune function in dairy cows related to energy balance and metabolic status in early lactation. AB - Two feeding experiments were carried out in 2 successive years with 28 cows of the Norwegian Red Cattle (NRF) in each experiment. The cows were randomly distributed into 4 groups and subjected to different feeding regimens from 1 month prior to calving until 12 weeks after calving. The experimental design was factorial (2 x 2) with respect to protein content of the concentrate (17.5% digestible crude protein (DCP) v.s. 12.5% DCP) and concentrate allowances (standard v.s. substandard allowances after calving). Silage was offered ad libitum. Samples for estimation of serum immunoglobulin-G, white blood cells and lymphocyte responses to the mitogens phytohemagglutinin, concanavalin A and pokeweed mitogen were collected 4 weeks prior to expected calving, and 2, 4 and 8 weeks after calving. The levels of milk immunoglobulin-G were estimated at calving and 2, 4 and 8 weeks after calving. A significant positive relationship was found between the estimated energy balance and the lymphocyte response to mitogens. Little evidence was found for the existence of a significant relationship between the immunologic parameters and plasma indicators of metabolic status. The lymphocyte response to phytohemagglutinin and levels of serum immunoglobulin-G increased, while levels of milk immunoglobulin-G decreased during the period from calving to 8 weeks after calving. Increased milk somatic cell counts were associated with a significant decrease in the lymphocyte responses to mitogens. PMID- 2596390 TI - Radionuclide uptake in experimentally induced meniscal lesions in rabbit knees. PMID- 2596391 TI - Vomitoxin and amino acid supplements in rat feed. PMID- 2596392 TI - In the physician's office: an interview with W. Ray Burns. PMID- 2596393 TI - Pharmacy practice acts: are they stifling professional growth? PMID- 2596395 TI - Redefining the ambulatory prescription business. AB - As outcomes management becomes more sophisticated and more widespread, the practice of managed care will be altered. Similarly, the ambulatory prescription business will be redefined to fit the needs of this environment. Potentially, the new definition could expand the ambulatory prescription business to encompass responsibility for the outcomes of the drug use process: clinical, quality-of life, and cost outcomes. A redefinition of the business requires that issues be addressed with respect to accountability and financing. PMID- 2596394 TI - Successful supervision: using interpersonal skills. PMID- 2596396 TI - Hazardous noise at a child care center. PMID- 2596397 TI - A method for correlating skin exposure to S-mustard vapor with skin damage. AB - An experimental procedure is described as a means for assessing the efficiency of skin-protecting measures against the vapors of hazardous substances. Bis(2 chloroethyl)sulfide (S-mustard) is used as the test substance. A continuous flow of S-mustard vapor is conducted through an exposure cell which is attached to the inner side of a rabbit's ear. From the difference in the concentrations measured before and behind the exposure cell, the absorption and the permeation rate of mustard into the skin is calculated. The skin damage, consisting of a reversible erythema, is quantified by measuring the optical transmittance of the exposed skin area during the following days and correlated with the respective absorption (dose) and exposure parameters (ct-product, with c = 3-50 ng/cm3 and t = 60 and 120 min). Reversible, i.e., completely healing, erythema are evoked by ct products in the range of 250-2000 ng.min/cm3 corresponding to doses from about 0.1 to 1.1 micrograms/cm2. A comparison with older data reveals that human skin, in this respect, is about eight times more sensitive than the inner side of the rabbit's ear. PMID- 2596398 TI - Respiratory health effects from occupational exposure to wood dust in sawmills. AB - Spirometric lung functions were recorded for 109 workers (mean age 26.4 +/- 8.2 yr) occupationally exposed (mean exposure 8.9 +/- 7.7 yr) to soft wood dust in local sawmills along with 88 unexposed controls (mean age 28.7 +/- 9.9 yr) belonging to the same socioeconomic status to assess the prevalence of respiratory impairment in the exposed population. The results of the study showed a significantly higher prevalence of overall respiratory impairment in the exposed group even after standardizing for smoking habits (p less than 0.001). The adjusted rate for respiratory impairment in the exposed group was 29.4% as compared to 2.2% observed in the unexposed controls. The pattern of respiratory abnormality observed in the sawmill workers was predominantly the restrictive type (28.4%), indicating lower levels of forced vital capacity (FVC) in the exposed group; while in the control group, there were none with lung restriction The prevalence of airflow limitation, however, was similar in the exposed workers (1.8%) and controls (2.2%), thereby, indicating that bronchial obstruction was independent of wood dust exposure. It is concluded that the dust exposure in sawmills is associated mainly with restrictive type of pulmonary impairment in the exposed workers. PMID- 2596399 TI - Medical monitoring of dioxin clean-up workers. AB - The effectiveness of the safety measures established to protect clean-up workers from 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure during clean-up operations of the most highly TCDD-contaminated area following the Seveso accident was evaluated. Clean-up workers (N = 36) and referent subjects (N = 36) underwent a 2-yr prospective controlled study aimed at detecting whether specific clinical and biochemical outcomes differed between the two groups. No cases of overt TCDD-related clinical disease occurred (i.e., chloracne, liver disease, peripheral neuropathy, porphyria cutanea tarda), and no clear-cut differences in biochemical outcomes between clean-up and reference workers were detected. The safety measures that were taken together with worker's compliance during clean-up operations were effective in preventing acute health effects. The safety, industrial hygiene, and health monitoring programs which were established following the Seveso accident should be applied as a minimum in similar situations. PMID- 2596401 TI - Proposed criteria for the selection of appropriate medical resources to perform medical surveillance for employees engaged in hazardous waste operations. Joint AIHA and ACGIH Hazardous Waste Committee. PMID- 2596400 TI - Biological monitoring of arsenic exposure of gallium arsenide- and inorganic arsenic-exposed workers by determination of inorganic arsenic and its metabolites in urine and hair. AB - In an attempt to establish a method for biological monitoring of inorganic arsenic exposure, the chemical species of arsenic were measured in the urine and hair of gallium arsenide (GaAs) plant and copper smelter workers. Determination of urinary inorganic arsenic concentration proved sensitive enough to monitor the low-level inorganic arsenic exposure of the GaAs plant workers. The urinary inorganic arsenic concentration in the copper smelter workers was far higher than that of a control group and was associated with high urinary concentrations of the inorganic arsenic metabolites, methylarsonic acid (MAA) and dimethylarsinic acid (DMAA). The results established a method for exposure level-dependent biological monitoring of inorganic arsenic exposure. Low-level exposures could be monitored only by determining urinary inorganic arsenic concentration. High-level exposures clearly produced an increased urinary inorganic arsenic concentration, with an increased sum of urinary concentrations of inorganic arsenic and its metabolites (inorganic arsenic + MAA + DMAA). The determination of urinary arsenobetaine proved to determine specifically the seafood-derived arsenic, allowing this arsenic to be distinguished clearly from the arsenic from occupational exposure. Monitoring arsenic exposure by determining the arsenic in the hair appeared to be of value only when used for environmental monitoring of arsenic contamination rather than for biological monitoring. PMID- 2596403 TI - Noise abatmement techniques in southern pine sawmills and planer mills. PMID- 2596402 TI - Fungi carried from farmers' work into farm homes. AB - Airborne fungal spore concentrations and main fungal genera were compared in rural and urban living environments in Finland during the winter. In addition to conventional viable fungal spore counts (based on the six-stage impactor sampling and cultivation), total spore concentrations were obtained by scanning electron microscope (SEM) investigation of filter samples. The viable spore counts were only 0.2%-25% of the number of total spore aggregates. A high correlation between these two methods was noted, however, at the recommended measuring ranges of the methods. In the farm houses, viable and total spore levels were 10(3) to 10(4) colony forming units/m3 (cfu/m3) and 10(4) to 10(5), spores/m3, respectively. These counts were 10-10(3)-fold higher than the concentrations in an urban apartment. The spore levels of farmers' homes, however, were somewhat lower than those observed in their cow barns. Aspergillus, Cladosporium, and Penicillium spores were present in both urban and rural environments. Actinomycetes and some fungal genera--such as Acremonium, Alternaria, Botrytis, and Chrysosporium--which were detected in cow barns and in farm houses, were not present in urban environment. The results indicated that airborne fungal spores may be carried from cow barns to farmers' homes. PMID- 2596404 TI - Acute and chronic respiratory effects of occupational exposure to ammonia. AB - In a soda ash plant, 58 workers exposed to mean airborne ammonia levels of 9.2 +/ 1.4 ppm were compared with 31 control workers with a mean exposure of 0.3 +/- 0.1 ppm. There were no differences between the groups in the reporting of respiratory or cutaneous symptoms, sense of smell, baseline lung function, or change in lung function over a work shift at the beginning and end of a workweek. No relationships between level or length of ammonia exposure and lung function results were demonstrated. PMID- 2596405 TI - A testing protocol for organic vapor respirator canisters and cartridges. PMID- 2596406 TI - Surface characteristics of asbestos fibers released from asbestos- cement products. PMID- 2596407 TI - A symposium: New trends in the treatment of rhythm disorders. February 6-7, 1989, Acapulco, Mexico. Proceedings. PMID- 2596408 TI - New observations on the mechanisms of antiarrhythmic actions of disopyramide on cardiac membranes. AB - Electrophysiologic effects of disopyramide on cardiac membranes were studied using the microelectrode technique applied to papillary muscles and the suction pipette whole-cell clamp method applied to isolated ventricular myocytes from guinea-pig hearts. In contrast to previous reports, the development and recovery from the Vmax blocks of action potentials by disopyramide and lidocaine were best expressed by 2 exponential functions, not 1, suggesting that there might be 2 different processes for the sodium current block. A near-therapeutic concentration (11 microM) of disopyramide depressed Vmax at frequencies of 0.1 to 2.0 Hz decreased action potential amplitude and shortened plateau phase in ventricular myocytes. Action potential duration was prolonged by the drug in most of the preparations but shortened in some. Disopyramide prolonged the refractory period and increased threshold current for excitation. The drug was also shown to depress both the calcium current and the delayed outward potassium current. These multiple actions of disopyramide may explain its variety of antiarrhythmic properties. PMID- 2596409 TI - An outlook on future trends in the treatment of rhythm disorders. PMID- 2596410 TI - Recent advances in understanding the mechanisms of drug-induced torsades de pointes arrhythmias. AB - QTU prolongation and polymorphic ventricular tachycardia "torsades de pointes" have occurred in association with electrolyte abnormalities and during therapy with class IA and III antiarrhythmic drugs. Several recent studies have suggested that the arrhythmia may be due to bradycardia-dependent early afterdepolarizations and triggered activity. These drugs produce 2 types of triggered activity, each with a different frequency profile. The possible role of each type in arrhythmia generation is discussed. The existing evidence suggest that drug-induced triggered activity may originate in the Purkinje system. Triggered activity can be abolished or prevented by various interventions that are also effective clinically. The results of studies at the cellular level, when compared with recordings of monophasic action potentials in vivo, suggest a role for early afterdepolarizations in torsades de pointes arrhythmias. PMID- 2596411 TI - Hemodynamic effects of antiarrhythmic drugs: negative inotropy versus influence on peripheral circulation. AB - The negative inotropic effect of nearly all antiarrhythmic drugs is one of the major drawbacks in antiarrhythmic therapy. This is particularly important in patients with reduced left ventricular function. In the clinical setting, different compounds have been described to depress cardiac function to a variable extent. The results are not uniform. In an experimental model, the hemodynamic effects of different drugs in the intact circulation as well as under isovolumic conditions in vivo after short cross-clamping of the aorta were tested. The results indicate that all antiarrhythmic compounds with the exception of class III drugs have a similar negative inotropic action on the heart muscle. However, the drugs have different effects on peripheral resistance, thus influencing cardiac afterload. These differences seem to be responsible for the different hemodynamic effects of the drugs observed clinically. PMID- 2596412 TI - Relevance of cellular to clinical electrophysiology in interpreting antiarrhythmic drug action. AB - The usefulness of cellular electrophysiologic techniques in elucidating the fundamental actions of antiarrhythmic drugs is contrasted with their apparent lack of relevance to the selection of drugs for the treatment of particular arrhythmias. Clinical electrophysiologists employ different techniques, but their results may be explained in terms of cellular drug actions. The varying clinical effects of class IA, IB and IC agents are due to differences in the speed of their attachment to, and detachment from, sodium channels. The role of sympathetic activity in arrhythmogenesis is complex, but again readily explicable in terms of the electrophysiologic cellular actions of stimulation of the individual types of adrenoceptors (alpha 1, alpha 2, beta 1 and beta 2) and the distribution of these receptors, and of the longterm effects of sympathetic deprivation, either by antisympathetic drugs (class II) or by sympathetic denervation. Delayed repolarization (e.g., by class III drugs or prolonged beta blockade) is antiarrhythmic because it is homogeneous, despite the incidental prolongation of QT. If, however, QT is prolonged by heterogeneity of conduction or repolarization, or by partial sympathetic denervation (long QT syndrome or post myocardial infarction), this indicates increased risk of arrhythmia. Finally, the efficacy of calcium antagonists (class IV) in supraventricular arrhythmias is attributable to the cellular electrophysiologic characteristics of sinoatrial and atrioventricular nodal and transitional elements. PMID- 2596413 TI - Treatment of ventricular arrhythmias in the coronary patient: what sort of patient? For which rhythm disorder? With which procedure? AB - In the patient with coronary artery disease, complex ventricular arrhythmias and frequent ventricular arrhythmias appear to be independent risk factors for subsequent death, particularly in patients who have had myocardial infarction. In patients with symptomatic arrhythmias, treatment must be instituted and tested during rigorous supervision of the patient. Using both the noninvasive Holter monitoring/exercise test procedure and invasive electrophysiologic testing, a beneficial antiarrhythmic response after institution of antiarrhythmic agents indicates improved prognosis. However, a negative treatment response during programmed stimulation does not necessarily indicate bad prognosis. This is particularly true for testing during amiodarone treatment. For unselected patients, routine antiarrhythmic treatment cannot currently be recommended. Continuing studies will show whether screening for electrical instability of the myocardium, and institution of antiarrhythmic therapy thereafter, will improve overall survival. If patients tolerate beta-blocking treatment, this should probably be instituted because reductions in mortality have been found, particularly in high-risk patients. PMID- 2596414 TI - Role of antitachycardia devices in the treatment of ventricular tachyarrhythmias. AB - Chronic recurrent ventricular tachycardia (VT) can be terminated reproducibly by programmed endocardial right ventricular stimulation. However, antitachycardia pacing is associated with possible acceleration of VT, while frequent occurrence of VT and discomfort of the patient can limit treatment with an automatic implantable cardioverter/defibrillator (AICD; Cardiac Pacemakers Inc.). The combined use of antitachycardia pacing (Tachylog pacemaker; Siemens-Elema) and AICD was therefore evaluated in 6 of 35 patients (aged 50 to 70 years, mean 60.1 +/- 7.7) in whom AICD had been implanted because of VT, which could be terminated by temporary overdrive pacing. With the interactive mode of the Tachylog, termination of VT by the pacemaker as well as by the AICD was assessed after implantation. In the automatic mode, the Tachylog functioned as a bipolar ventricular inhibited (VVI) device with antitachycardia burst stimulation: 2 to 5 stimuli, interval 260 to 300 ms, 1 to 2 interventions. During follow-up of 32 +/- 17 months, the Tachylog terminated VT reliably 50 to 505 times per patient. When burst stimulation accelerated VT, termination was achieved by AICD discharge. Thus, drug-resistant VT can be terminated by antitachycardia pacing avoiding patient discomfort. In case of acceleration, VT can be controlled by the AICD. A universal pacemaker should combine antibradycardia and antitachycardia pacing with backup cardioversion/defibrillation mode. PMID- 2596415 TI - Electrophysiologic basis of catheter ablation in atrial flutter. AB - A reentrant mechanism is believed to be responsible for atrial flutter. The recent development of the entrainment criteria further supports this theory, and there is a general consensus that circus movement is the underlying abnormality that supports this arrhythmia. In most clinical studies, abnormal fragmented (or double spike) electrograms, suggesting the presence of areas of localized slowing of conduction or block, have been reported. They are almost always recorded in the lower and posterior portion of the right interatrial septum, but also frequently in the high lateral portion of the right atrium. The determination of their involvement in the reentry pathway is important for designing curative procedures such as surgery or ablation. The low atrial septal area surrounding the mouth of the coronary sinus was suspected as being the critical area of slow conduction in atrial flutter. Rapid pacing at that site can yield a surface electrocardiographic pattern similar to the clinically occurring arrhythmias. Additionally, the flutter circuit can be accelerated during atrial pacing at fixed and slightly faster rates than the intrinsic tachycardia rate--the so called entrainment phenomenon. When entrainment criteria are fulfilled, tachycardia termination being by definition ruled out, any concomitant recorded local type II block identifies an area that must be outside the circuit. Such local block may be recorded either spontaneously or during entrainment and therefore helps in identifying atrial slow conduction areas that do not belong to the reentrant path. This approach was applied to identify the optimal ablation site in 8 patients with long-standing drug resistant atrial flutter. In 7 of 8 patients, we were able to identify a fragmented potential in the low posteroseptal area during sustained atrial flutter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596416 TI - Treatment of rhythm disorders by endocardial fulguration. AB - The fulguration procedure was originally introduced for the treatment of supraventricular arrhythmias by a pervenous interruption of His bundle conduction. This procedure has been extended to the treatment of almost any cardiac arrhythmia resistant to antiarrhythmic drug therapy. Recent results suggest that ablation could be selectively applied to the site of abnormal conduction. Overall results obtained at the Jean Rostand Hospital are reported for a series of 104 patients ranging in age from 14 to 83 years with atrial, junctional and ventricular tachycardias. The follow-up extends up to 65 months. Clinical efficacy, defined as a control of the arrhythmias by fulguration used alone or in association with drug therapy that was previously ineffective, lead to a success rate ranging from 80 to 85%. Mortality was less than 10% in the worst situation (chronic resistant ventricular tachycardia). Mortality was always related to inappropriate protocols. Therefore, fulguration, which was originally reserved to treat the most difficult cases, is now considered for non-life threatening but incapacitating arrhythmias. Despite these results the technique is not simple. Fulguration should be performed by groups knowledgeable in electrophysiology and with expertise in high voltage electricity and biophysics. PMID- 2596417 TI - Surgical management of tachyarrhythmias. AB - In this study of surgical procedures for various tachyarrhythmias, Wolff Parkinson-White syndrome comprised most of the cases. An endocardial approach was used to ablate accessory pathways. Additional use of cryocoagulation after surgical incision of the atrium, previously routinely performed, is at present only done occasionally for septal accessory pathways. Ventricular tachycardia (VT) was the next most frequent condition. The surgical procedures for ischemic and nonischemic VTs are completely different, although both are based on the principle of complete electrophysiologic mapping. For ischemic VT, surgery consists of resection of the left ventricular aneurysm and excision or cryocoagulation of the endocardium, or both. For nonischemic VT, either excision of the entire thickness of the myocardium (2.0 X 2.5 cm on average) at the earliest excitation site of the right ventricle and cryocoagulation of the area of delayed potential or only incision and cyrocoagulation of the left ventricle were performed to avoid reduction of the left ventricular cavity. Ectopic atrial tachycardia was cured by excision of the earliest excitation site without use of a heart-lung machine, when the focus was located in the atrial free wall. Other successful treatments were of reentrant atrial tachycardia by cryocoagulation, atrial flutter by cryocoagulation of impulse pathways at the coronary sinus and around the atrioventricular node, and a new surgery for atrial fibrillation and flutter, which retained sinus rhythm. Johnson's procedure was used for surgical ablation of atrioventricular nodal reentrant tachycardia. PMID- 2596418 TI - Surgical alternatives for supraventricular tachycardias. AB - Since Sealy's pioneering surgical intervention for Wolff-Parkinson-White syndrome, surgical electrophysiologic interventions have been developed for all supraventricular arrhythmias. The surgical rationales are based on the site of origin of the arrhythmic mechanism and the associated pathology that characterizes the "arrhythmogenic substrate." The Wolff-Parkinson-White syndrome is characterized by an accessory atrioventricular (AV) connection distinct from the AV node-His bundle system. It is associated with AV reentrant tachycardia or atrial fibrillation, or both, with fast ventricular responses through the accessory pathway. The current surgical management involves ablation of the accessory pathway using either an endocardial or an epicardial approach. Surgical ablation is associated with high efficiency and low morbidity. Epicardial dissection of the accessory pathway on the beating heart has helped to localize variant accessory pathways associated with Coumel's tachycardia or the Mahaim fiber. AV nodal reentrant tachycardia can be cured using direct AV nodal dissection (or perinodal cryoablation). Atrial flutter can be interrupted by cryoablation of the arrhythmogenic substrate located in the coronary sinus orifice region. The chronotropic atrial function, abolished by incessant or paroxysmal idiopathic atrial fibrillation, can be restored using the corridor operation (sinus node-AV node insulation). The success of surgical intervention in atrial tachycardias is uncertain, but it may be an option in selected patients with resistant atrial tachycardias. PMID- 2596419 TI - Relation of body size and composition to clinical biochemical and hematologic indices in US men and women. AB - Small but significant variations in clinical biochemical indices may be of great biological significance. Earlier studies conducted on small, chronically ill, hospitalized, anemic, and/or malnourished population samples suggested associations between body size and composition and indices of iron metabolism, serum protein, and plasma cholesterol. We studied a large, nonhospitalized probability sample of women and men in the First US Health and Nutrition Examination Survey (NHANES I) to characterize these associations. Greater weight, stature, body mass index (BMI), skinfold thickness, and lean body mass (LBM) are associated with higher hemoglobin, hematocrit, and total iron-binding capacity. LBM and body fat are weakly related to serum albumin concentrations in men and to serum total protein concentrations in women. Total cholesterol concentrations are directly associated with weight, body fat, and LBM and are more strongly associated with central than peripheral obesity. Constitutional factors may be important for clinical assessment and for interpretation of epidemiologic studies. PMID- 2596420 TI - Chemical determination of human body density in vivo: relevance to hydrodensitometry. AB - A chemical approach to establishing human body density in vivo was developed by combining recently developed noninvasive methods. Four compartments were measured: protein (P; prompt-gamma neutron activation), water (A; 3H2O dilution), mineral (M; dual-photon absorptiometry and delayed-gamma neutron activation), and fat (F; dual-photon absorptiometry). By this model body weight is equal to P + A + M + F. This approach was applied to 13 healthy adults (8 females and 5 males). The four compartments accounted for greater than 97% actual body weight. Calculated density based upon composition agreed within 0.6 +/- 0.4% (mean +/- SD) with density (D) measured by hydrodensitometry [calculated D (g/cc) = 0.86 measured D +0.15; r = 0.94, p less than 0.001]. The average calculated lean (P + A + M) density of 1.096 +/- 0.007 g/cc agreed closely with three classic human cadaver studies (1.100 g/cc). This multicompartment approach provides a new opportunity to estimate human body density in vivo and to refine body composition methods based upon an assumed but inadequately validated constant lean density. PMID- 2596421 TI - Measurement of extracellular water volume by bromide ion chromatography. AB - Extracellular body water can be determined from plasma bromide dilution. Plasma Br is separated from other anions by ion chromatography and is detected at an ultraviolet wavelength of 210 nm. Plasma proteins are removed by ultrafiltration, and interference by plasma chloride is minimized by dilution and the use of 5 mmol NaCl/L as the eluant. Human plasma samples were spiked with known quantities of Br (between 37.54 and 125.14 mumol/L) and were measured by ion chromatography. The results were reproducible to within 0.72 mumol/L (SD) and differed from the gravimetric values by -1.88 +/- 4.27 mumol/L (mean +/- SD). The difference, however, was not significantly different from 0 (p = 0.19). Extracellular water volumes of 10 newborn minipigs measured by Br dilution by using the chromatographic technique (400 +/- 63 mL/kg) were comparable with literature values reported for premature infants. PMID- 2596422 TI - Fatness and obesity of the parents of obese individuals. AB - As shown in 1419 pairings of obese probands with their parents drawn from a larger series of greater than 9000 proband-parent pairings, the fathers and mothers of obese probands are of increased fatness level (+0.27 Z scores) and more often obese than expected (odds ratio 1.50 overall). However, the tendency towards increased fatness and a greater prevalence of obesity among the parents of obese probands bears a curvilinear relationship to the age of the proband, being least when the probands are young, peaking when the sons and daughters are teen-agers, and declining thereafter. Parents of lean probands in turn tend to be lean themselves (averaging -0.25 Z scores) and least often obese when their progeny are teen-aged. As shown in a two-generational context, familial obesity is best demonstrated in adolescents and their parents, either reflecting years spent in common or a specific etiology for adolescent-onset obesity. PMID- 2596423 TI - Adaptation of energy metabolism of overweight women to alternating and continuous low energy intake. AB - To investigate whether a slimming diet based on alternating (low with normal) energy intakes could counteract a decrease in energy requirement, 24-h energy expenditure (24EE), sleeping energy expenditure (sleeping EE), and physical activity were determined in a respiration chamber in 27 overweight women: before weight reduction and after 4 and 8 wk of slimming. Daily alternating and continuous slimming diets were supplied. Average weight losses over 8 wk of slimming were 6.9-9.0 kg. After 8 wk at low energy intake, 24EE had declined by 12-16% (from 2328 +/- 219 to 1987 +/- 204 kcal, mean +/- SD). Sleeping EE had declined by 7-13% (from 64 +/- 6 to 57 +/- 6 kcal/h). Measurements of physical activity indicated a reduction of spontaneous physical activity during slimming. Alternating low energy intake did not prevent 24EE from declining. The reduction in 24EE was determined by a decrease of body weight, dietary induced thermogenesis (in proportion to caloric restriction), and physical activity. There seems little reason to consider other adaptive mechanisms. PMID- 2596424 TI - Effects of cardiac stress during a very-low-calorie diet and exercise program in obese women. AB - To assess the safety of very-low-calorie diets (VLCDs), stress tests known to induce arrhythmias in susceptible patients were performed in 24 obese women on a VLCD (660-720 kcal/d) for 6 wk. Half of the subjects had diet only (DO) and half underwent supervised exercise (DE) four times weekly. Five control subjects ate a balanced, moderately low-calorie diet (approximately 1400 kcal/d). Stress tests included maximal and submaximal (85%) exercise, psychological stress, and isometric handgrip tests, all with constant electrocardiogram (ECG) monitoring. Twenty-four-hour Holter monitors at weeks 0 and 6 and weekly resting ECGs were obtained. DO and DE lost similar amounts of weight. There were no changes in QT intervals or in voltage or width of the QRS complex on resting ECG and no arrhythmias on Holter monitoring. These data support the safety of VLCDs containing greater than or equal to 650 kcal/d and adequate amounts of high quality protein, vitamins, and minerals for use for periods of at least 6 wk in normal, healthy obese women. PMID- 2596425 TI - Metabolic effects of a single administration of growth hormone on lipid and carbohydrate metabolism in normal-weight and obese subjects. AB - The effects on lipid metabolism of a single intramuscular dose of SR 29001 (0.15 U/kg body wt), a biosynthetic human growth hormone (hGH), were explored in a double-blind randomized crossover vs a placebo study of six normal-weight and six obese subjects (Quetelet Index greater than 120%). Circulating hGH concentrations reached means of 35 and 28 ng/mL in the normal-weight and obese subjects, respectively. Free fatty acids increased in both groups (p less than 0.05); increases in beta-hydroxybutyrate and acetoacetate concentrations were more moderate (NS). Plasma glucose increased significantly despite a significant increase in insulin (p less than 0.002). The lipolytic effect persisted after a standardized 950-kcal meal eaten 5 h after hGH administration. A delayed increase in somatomedin-C and decreases in blood urea and total cholesterol were also observed (p less than 0.05). Despite increased insulin secretion, biosynthetic hGH produced a significant increase of lipolysis in both groups, which was only partially suppressed by food. PMID- 2596426 TI - Milk composition and volume during the onset of lactation in a diabetic mother. AB - Milk volume and composition were examined in a diabetic mother on days 3-7 postpartum. By day 5 milk volume produced and concentrations of sodium, potassium, chloride, lactose, protein, calcium, magnesium, and citrate were within limits of a reference population. Fat content of the milk was slightly lower. Free fatty acids were 2% of total lipid on day 3 but increased to 23% on days 4-7, suggesting impaired esterification in the mammary gland. Total milk lipoprotein lipase increased approximately fourfold during days 4-5. Other changes were 1) low cholesterol content, only one-fifth of normal milk; 2) decreased medium-chain fatty acids, suggesting impairment of fatty acid synthesis in the mammary gland; 3) increased oleic acid; and 4) high concentrations of polyunsaturated fatty acids, suggesting increased chain elongation. These results suggest that diabetes produces changes in lipid metabolism in the mammary gland that alter the composition of milk produced by the diabetic mother. PMID- 2596427 TI - Fat emulsion particle size: influence on the clearance rate and the tissue lipolytic activity. AB - In lipid emulsions for parenteral use the mean particle diameter of the droplets in the 20% emulsions is larger than in the 10% emulsions. In long-chain triglyceride emulsions it is greater than in medium-chain triglyceride emulsions. As the particle diameter decreases, the total interfacial area increases, as does the lipoprotein lipase (LPL) and hepatic lipase (HL) activity. For a given quantity of triglycerides and phospholipids the lipolytic activity is proportional to the total interfacial area. A doubling of the phospholipid concentration is accompanied by a small reduction in the activity of both enzymes. In going from long-chain to medium-chain triglycerides, there is an acceleration in the clearance rate of infused lipid. For a similar emulsion, the clearance rate decreases as the particle size decreases. It seems plausible that the larger the mean droplet diameter, the greater the participation of the reticuloendothelial system in the clearance. PMID- 2596428 TI - Comparison of the effect of canola oil and sunflower oil on plasma lipids and lipoproteins and on in vivo thromboxane A2 and prostacyclin production in healthy young men. AB - The effect of dietary fatty acid composition on plasma lipids and eicosanoid production was studied in normolipidemic men. Approximately 75% of the fat in the diet was provided by a mixture of fats (MF) during the 6-d pre and postperiods and either canola oil (CO) or sunflower oil (SO) during the two 18-d experimental periods. Saturated, monounsaturated, and polyunsaturated fatty acids provided 14%, 15%, and 7%; 5%, 20%, and 10%; and 7%, 7%, and 22%, respectively, of total dietary energy in the MF, CO, and SO diets, respectively. The CO and SO diets produced similar decreases in plasma total (20% and 15%, respectively) and low density lipoprotein (25% and 21%, respectively) cholesterol. Plasma high-density lipoprotein cholesterol and triglyceride concentrations were not altered by either fat source. Bleeding time was longer and in vivo 1-keto-PGF1 alpha production was greater (p less than 0.05) when on the CO diet than when on the MF diet. The hypocholesterolemic and antithrombotic effects of the CO diet were equivalent to those of the SO diet. PMID- 2596429 TI - Hypercysteinemia and delayed sulfur excretion in cirrhotics after oral cysteine loads. AB - Biosynthesis of cysteine from methionine via the hepatic transsulfuration pathway is impaired in some cirrhotic patients, who therefore might require cysteine in the diet. However, because further metabolism of cysteine also occurs primarily in the liver, the metabolic clearance of this amino acid could be impaired in cirrhosis. We administered oral loads of L-cysteine to cirrhotic patients and healthy volunteers. Plasma cyst(e)ine (free and protein-bound cysteine, and 1/2 cystine) and urinary sulfur-containing constituents were measured at various times postload. Cirrhotic subjects exhibited a greater maximal plasma cyst(e)ine concentration and plasma elimination half-life (t1/2) and a delayed excretion of metabolic end products after an oral L-cysteine load. The postload increase in total plasma cyst(e)ine was accounted for primarily by an increase in the disulfide form (cystine). These studies show that cirrhotics have an impaired ability to clear cyst(e)ine from the plasma. PMID- 2596430 TI - Exchange of 3-methylhistidine in the splanchnic region in human infection. AB - This investigation was undertaken to determine the splanchnic exchange of 3 methylhistidine (3MH) in infection. Hepatic vein, femoral vein, and radial artery catheterizations were performed in 12 febrile patients with infections of varying severity. Differences in arteriovenous 3MH, analyzed by high-performance liquid chromatography, were multiplied by the plasma flows, determined by a dye dilution technique. The mean splanchnic efflux was 0.062 +/- 0.180 mumol/min (mean +/- SD) with uptake occurring in five patients. The splanchnic uptake was significantly (p less than 0.001) correlated with the urinary 3MH excretion and the peripheral release from the leg. It is concluded that in human infection, splanchnic 3MH release is low and in patients with high rates of myofibrillar catabolism there may even be an uptake. The urinary 3MH excretion is still a marker of myofibrillar protein breakdown because it correlates well with the release from the leg, regardless of whether the patient has a splanchnic uptake or a release. PMID- 2596431 TI - Genetic polymorphism of glutamate-pyruvate transaminase (alanine aminotransaminase): influence on erythrocyte activity as a marker of vitamin B-6 nutritional status. AB - A new, sensitive, two-step method free from interference by hemoglobin that measures erythrocyte glutamate-pyruvate transaminase (E-GPT) activity is described. Several aspects of E-GPT activity as an index of vitamin B-6 nutritional status were investigated with this method. 1) GPT shows a structural genetic polymorphism with two common alleles resulting in three phenotypes. In a population study (n = 92) E-GPT activity differed significantly (p less than 0.001) among the three phenotypic groups. Plasma pyridoxal-5'-phosphate concentrations in the three groups did not differ significantly. Therefore, E-GPT activity can only be used to assess vitamin B-6 nutritional status if GPT phenotype is accounted for. 2) Pyridoxine supplementation (10 mg/d) significantly (p less than 0.0001) increased E-GPT activity and decreased (p less than 0.0001) the percentage stimulation by pyridoxal-5'-phosphate in vitro although the absolute amount of in vitro stimulation by pyridoxal-5'-phosphate changed only marginally. 3) Inorganic phosphate inhibits in vitro activation of E-GPT by pyridoxal-5'-phosphate. PMID- 2596432 TI - Folate absorption in alcoholic pigs: in vivo intestinal perfusion studies. AB - To determine if impaired intestinal absorption contributes to the folate deficiency observed in chronic alcoholics, we assessed in vivo folate absorption in Hanford mini-pigs fed ethanol with an adequate diet. Sixteen minipigs were pair-fed diets supplemented with ethanol or sucrose to 60% of total calories for 11 mo. In the ethanol-fed pigs peak blood alcohol concentrations averaged 28 mmol/L, serum alanine transaminase and aspartate transaminase activities were elevated, and liver histology showed a centrilobular distribution of succinate dehydrogenase. Tissue folate concentrations were comparable in both groups. The jejunal uptake of folic acid, measured by intestinal perfusion, was similar in both groups of animals and was not affected by acute exposure to 445 mmol/L ethanol. The in vivo hydrolysis of polyglutamyl folate was reduced by 35% in one ethanol-fed minipig. Decreased hydrolysis of polyglutamyl folate may represent an early step in the development of folate deficiency in chronic alcoholics. PMID- 2596434 TI - Hemoglobin as a predictor of response to iron therapy and its use in screening and prevalence estimates. AB - The use of hemoglobin as a predictor of response to iron therapy, for screening, and for prevalence estimates was studied. An Fe supplementation trial was performed in Quito, Ecuador, in which 412 pregnant women were randomly assigned to treatment and control groups. Women in the treatment group received 390 mg ferrous sulfate/d for 2 mo. The prevalence of Fe deficiency as defined by response to therapy was found to be 60.8%. Sensitivity and specificity were calculated at various cutoff points of hemoglobin. The estimates of sensitivity and specificity allow for the use of hemoglobin in screening for Fe deficiency anemia and in the estimation of the prevalence in populations with characteristics similar to those found in the sample of pregnant women in Quito. Hemoglobin was shown to be a good predictor of response to Fe treatment and a good estimate of prevalence of Fe deficiency when prevalence is high. PMID- 2596433 TI - Folate absorption in alcoholic pigs: in vitro hydrolysis and transport at the intestinal brush border membrane. AB - We used the miniature pig to evaluate the effect of ethanol ingestion on the hydrolysis of pteroylpolyglutamate and on the uptake of pteroylmonoglutamate (PteGlu) by the intestinal brush border membrane, processes that are required for folate absorption. After feeding ethanol or sucrose at 60% of calories for 11 mo, the uptake of PteGlu by jejunal brush-border-membrane vesicles was similar in both groups of animals. Jejunal brush border pteroylpolyglutamate hydrolase was decreased by one-half in the ethanol-fed group. Jejunal brush-border-membrane fluidity, measured by fluorescence polarization, was similar in both groups. Acute exposure of the jejunal vesicles to ethanol increased membrane fluidity and decreased hydrolase activity but had no effect on PteGlu transport. Inhibition of jejunal folate hydrolase by chronic exposure to ethanol may be an early effect in the pathogenesis of folate malabsorption and deficiency in chronic alcoholism. PMID- 2596435 TI - Dietary calcium, phytate, and zinc intakes and the calcium, phytate, and zinc molar ratios of the diets of a selected group of East African children. AB - Dietary zinc, calcium, and phytate intakes of 66 rural Malawian children aged 4-6 y were determined during three seasons on the basis of weighed food records and analyzed food composition data. Height and weight measurements were also recorded and hair samples were collected for zinc analysis. Seasonal daily zinc, calcium, and phytate intakes of females ranged from 6.2 +/- 1.7 to 6.8 +/- 2.1 mg (mean +/ SD), from 335 +/- 170 to 401 +/- 257 mg, and from 1621 +/- 660 to 1729 +/- 592 mg, respectively and, for males, 7.0 +/- 1.7 to 8.0 +/- 2.3 mg, 342 +/- 164 to 473 +/- 310 mg, and 1857 +/- 530 to 2161 +/- 684 mg, respectively. Cereals provided greater than 42% of dietary zinc. Seasonal mean molar ratios of phytate to Zn and Ca x phytate to Zn [per 1000 kcal (4.2 MJ)] and the median Ca to phytate molar ratio ranged from 24 to 27, 151 to 188 mmol/1000 kcal (4.2 MJ), and 3.1 to 3.4, respectively. Over 78% of the children consumed diets with phytate-to Zn and Ca x phytate.Zn-1 . 1000 kcal-1 molar ratios above values suggested to jeopardize zinc status. Correlations between hair zinc, phytate-to-Zn, and Ca x phytate.Zn-1 . 1000 kcal-1 molar ratios suggest that high phytic acid intakes may compromise zinc status in these children. PMID- 2596436 TI - Determination of zinc and copper absorption at three dietary Zn-Cu ratios by using stable isotope methods in young adult and elderly subjects. AB - Nine young men and six elderly men and women ingested low-zinc, low-copper, and adequate diets for 2-wk periods. The Zn-Cu ratios averaged 2:1, 15:1, and 5:1. On day 8 of each period, subjects ingested doses of 70Zn and 65Cu so that net absorption could be determined. Zn absorption on the adequate diet was 39 +/- 3% (means +/- SEM) in young subjects and 21 +/- 1% (p less than 0.05) in the elderly subjects. During the low-Zn period, Zn absorption was higher as compared with that on the adequate diet in both young (64 +/- 5%, p less than 0.05) and elderly subjects (43 +/- 7%, p less than 0.05). Cu absorption on the adequate diet was 60 +/- 4% and 53 +/- 2% in young and elderly subjects, respectively. During the low Cu period, Cu absorption was higher as compared with that on the adequate diet in the elderly subjects (67 +/- 4%, p less than 0.05). Cu absorption was higher in six of seven young subjects on the restricted Cu diet (p greater than 0.05). The effect upon absorption of the change in the Zn-Cu ratio was less than the effect of dietary restriction. PMID- 2596437 TI - A new approach to characterize whole-gut transit in infants with use of a nonabsorbable intestinal marker. AB - To characterize mouth to anus transit of intestinal contents, polyethylene glycol (PEG) was given as an intestinal marker to 11 healthy infants, and daily fecal collections were analyzed for PEG concentration per unit of dry stool weight for 9-15 d. Fecal PEG excretion followed first-order kinetics. Thus, half-life (t1/2) and volume of distribution (Vd) of PEG in the gut could be computed for each of seven infants who received continuous daily PEG doses and t1/2 only for four infants who received a single PEG dose. t1/2 of PEG in the gut was 0.99 +/- 0.48 d (means +/- SD). Vd for PEG in the gut was 18.74 +/- 15.38 g of fecal dry weight. We propose that whole-gut transit be expressed in terms of t1/2 and Vd of intestinal contents because these may better characterize the changes in intestinal transit that occur with disease or dietary modifications. PMID- 2596439 TI - Glycemic response to food. PMID- 2596438 TI - Digestibility of starch: incomplete gelatinization or retrogradation? PMID- 2596440 TI - Naloxone challenge as a biological predictor of treatment outcome in opiate addicts. AB - Thirty seven consecutive applicants to methadone maintenance were assessed for depression and for level of opiate dependence using a 0.8-mg naloxone challenge. Nineteen of the applicants met DSM-III-R criteria for current major depression. At 3-month follow-up, high naloxone challenge test (NCT) scores at intake (high levels of opiate addiction) were found to predict poor program retention and elevated symptoms of depression at follow-up. Reports of heavy current drug use at intake were also associated with poor program retention and with high frequencies of positive urine screens for illicit substances during treatment. Level of addiction and reported amount of drug use at intake independently predicted program retention with a multiple correlation of 0.46 (P less than .01). Although NCT predicted depression at follow-up, depression at intake did not significantly predict treatment outcome, and NCT score predicted outcome independently of psychopathology. PMID- 2596441 TI - Outpatient treatment of PCP abusers. AB - Despite the persistence of phencyclidine (PCP) abuse as a public health problem in many urban areas of the United States, there are no published data on outpatient treatment outcome. We studied 37 unselected male PCP abusers (mean age 32 years, 73% Black, 19% married, 68% unemployed) who attended at least one outpatient treatment session at the Brentwood Division, West Los Angeles VA Medical Center. Subjects had smoked PCP for an average of 7 years, with 84% using it at least weekly (38% daily) and 76% using other drugs (alcohol, marijuana, or cocaine). All subjects reported psychological dependence on PCP (i.e., liking PCP use and difficulty stopping despite adverse consequences), while none reported a physiological withdrawal syndrome when stopping PCP use. Subjects stayed in treatment an average of 21 weeks (range 1-155 weeks), attending an average of 68% of the group meetings. PCP was detected in weekly urine samples 78% of the time, with verbal self-report of recent PCP use occurring before 29% of the group meetings. Four subjects (11%) achieved at least 1 year of abstinence, 10 (30%) transferred to residential treatment or a community recovery home, 16 (48%) dropped out of treatment, and two (6%) were jailed. Treatment outcome was not significantly associated with subject characteristics. Age was the only subject characteristic that significantly predicted length of stay (r = .40). PMID- 2596442 TI - Cocaine abuse and violent death. AB - One hundred and fourteen Los Angeles County Coroner's cases found to be positive in drug screening for the presence of cocaine were studied to determine the relationship between cocaine abuse and violent death. Of these 114 victims, 70 (61.4%) died a violent death--over 68% of these as shootings and stabbings. Fourteen of the violent death victims (20%) were found to have been behaving in a violent manner just prior to their death. Violence seems to be clearly connected to the use and abuse of cocaine. PMID- 2596443 TI - Correlates of self-reported early childhood aggression in subjects volunteering for drug studies. AB - The construct validity of a retrospective self-report measure of early childhood aggression, the Early Experience Questionnaire (EEQ), was assessed in a sample of substance abusing volunteers for drug studies at a research center in Baltimore. In contrast to the diagnosis of Antisocial Personality Disorder (APD), EEQ scores were not only associated with adult aggression, criminality, and substance abuse, but were also highly correlated with a cluster of measures reflecting emotionally reactive impulsivity. Correlations of the EEQ with the Minnesota Multiphasic Personality Inventory confirmed earlier findings obtained on a sample of alcoholics. Over and above the predictive influence of APD, early childhood aggression had some predictive influence on the incidence and severity of substance abuse but a substantial influence on the prediction of criminality. PMID- 2596444 TI - Alcohol, drug, and mental health problems among Jewish and Christian men at a university. AB - Data from a questionnaire sent to 704 male university students and nonacademic staff were reanalyzed to compare self-reports of drug and alcohol intake patterns and problems as well as family histories of psychiatric disorders for Jewish (N = 110, Group 1) and Christian men (N = 594, Group 2). Although the two groups did not differ significantly on the quantity and frequency of alcohol intake, men in Group 2 were more likely to report at least one episode of heavy drinking and alcohol-related problems, and their responses indicated a higher rate of a family history of alcoholism. There were no differences across the groups on the proportion of lifetime drug use and related difficulties, or on the family histories of other psychiatric disorders. The results are consistent with previous studies demonstrating a lower prevalence of heavy drinking and related problems among Jews. PMID- 2596445 TI - Psychiatric screening of alcohol and drug patients: the validity of the GHQ-60. AB - The 60-item General Health Questionnaire (GHQ) and the National Institute of Mental Health Diagnostic Interview Schedule (DIS) were administered to 501 patients presenting for assessment or treatment of alcohol or drug problems at the Addiction Research Foundation, Toronto, Canada. The GHQ proved to be a useful, if limited, instrument for routine screening for psychiatric disorders other than substance abuse in this population. The sensitivity or "utility" of the test at the optimum threshold score was considerably lower in this sample than in medical or community samples. Receiver Operating Characteristic (ROC) analysis suggests a need for an upward revision of the cut-off score to 23/24 inpatients with alcohol or drug problems. At this threshold, sensitivity was 69%, specificity 75%, positive predictive value 77%, negative predictive value 66%, and overall misclassification rate 29%. A definition of "caseness" was used that included all DIS Axis I disorders with the exception of substance use and "cognitive impairment." Sensitivity of the GHQ was highest for the affective disorders (79%). False negatives accounted for the bulk (61%) of the misclassification rate. At the threshold score of 23/24, positive predictive values were greater for the unemployed and for patients with either no current substance use disorder or with both alcohol and drug disorders. PMID- 2596446 TI - AIDS-related illness and AIDS risk in male homo/bisexual substance abusers: case reports and clinical issues. AB - Little has been written about the treatment of substance use disorders among seropositive HIV patients or high-risk seronegative substance abusers. Demographic and clinical characteristics, along with treatment issues, were examined based on experience with 18 patients in a substance abuse program in a university medical center (3 AID, 3 ARC, 9 seropositive only, and 3 seronegative high risk). Scores on a substance abuse rating scale were extremely high. Most of them abused three or more different substances, had used drugs parenterally, had more than 50 sex partners, and/or had received previous substance abuse treatment. Affective disorder, suicide attempt, and antisocial personality were frequent in this group. About half of the patients complied with treatment and showed improvement in their substance disorder. Several common themes in the management of these patients are described. PMID- 2596447 TI - Controversies, dilemmas, and dialogues. Recommendations for antibiotic prophylaxis before endoscopy. PMID- 2596448 TI - Endocarditis prophylaxis and gastrointestinal procedures. PMID- 2596449 TI - Barrett's esophagus in patients with symptomatic reflux esophagitis. AB - We evaluated the frequency with which Barrett's esophagus (BE) occurs in patients with symptomatic reflux esophagitis, and compared the clinical endoscopic and manometric features of patients with Barrett's esophagus with those of patients who had non-Barrett's esophagitis (NBE). The effect of 6 months' medical treatment on BE patients was reevaluated by repeating manometry, endoscopy, and biopsy. Esophageal manometry was performed by perfusion technique and endoscopic biopsies were obtained. There were 180 patients; 20 (11%) were found to have BE. The vast majority of BE patients were caucasians. BE patients had symptoms of gastroesophageal reflux for a longer time than did NBE patients. Mean lower esophageal sphincter pressure in BE patients was lower than that in NBE patients. On medical treatment, the severity of esophagitis as judged by endoscopic criteria in BE patients was reduced, but there was no increase in lower esophageal sphincter pressure and no regression of the columnar epithelium. PMID- 2596450 TI - Esophageal electromyography in scleroderma patients with functional dysphagia. AB - Simultaneous recordings of myoelectric and manometric activities of the esophagus were made in two groups of patients with scleroderma. Group A consisted of patients who suffered from functional dysphagia that had appeared recently, and who had a normal size esophagus when examined radiographically. Patients in group B had complained of functional dysphagia for several years and showed a dilated hypotonic esophagus on x-ray. A control group of five normal subjects was also examined in the same manner. The study was carried out by means of a peroral probe with two pairs of suction-needle electrodes and two manometric side-hole catheters positioned at the same levels as the electrodes. Standard manometric examination of the esophagus was carried out in all patients. Normal subjects after each deglutition showed a propagated burst of spikes in correspondence with the ascending phase of the peristaltic wave, whereas, in the period between deglutitions, rare spikes and no pressure waves were recorded. Group A patients were characterized by the frequent appearance during the interdeglutitive period of spontaneous rhythmic sequences or bursts of spikes associated with pressure waves. In these patients, repetitive nonpropagated spike bursts with a higher than normal amplitude and duration were observed after deglutitions in association with high-amplitude nonpropagated repetitive pressure waves similar to those observed in diffuse esophageal spasm (DES). Five of the seven group B patients showed spike bursts and pressure waves with both amplitude and duration markedly lower than normal. The remaining two patients from group B presented no spike bursts or pressure waves at all. Standard manometry demonstrated findings equivalent to those obtained via electromyography (EMG) in all patients of group B and in only two patients of group A. In conclusion, the functional dysphagia of patients with scleroderma can be attributed to two different motor disorders. The first one is characterized by disorganized myoelectric hyperactivity and may have a manometric appearance similar to that of diffuse spasm. The second one is characterized by a marked decrease in myoelectric activity and corresponds to the classic manometric finding of scleroderma involvement of the esophagus. Both these myoelectric patterns seem to be related to subsequent stages of esophageal scleroderma involvement. PMID- 2596451 TI - Chronic hoarseness secondary to gastroesophageal reflux disease: documentation with 24-h ambulatory pH monitoring. AB - Gastroesophageal reflux (GER) has been implicated in otolaryngologic problems, particularly chronic hoarseness that cannot be attributed to other causes. To study this relationship, we used 24-h ambulatory intraesophageal or dual pharyngoesophageal pH monitoring in 33 patients with chronic hoarseness and laryngeal lesions suggestive of acid irritation. Twenty-six of the patients (78.8%) had pH evidence of severe GER, being at least three times greater than the upper limit of normal. In contrast to 19 patients with proven esophagitis, this GER was worse in the upright position. Of 15 patients with both pharyngeal and esophageal probes, three had esophagopharyngeal reflux, and two had atypical unexplained pharyngeal decreases in pH to below 4.0. Less than half of the 33 patients had the typical symptoms of GER, and standard esophageal tests usually yielded normal findings. Occult GER, predominantly in the upright position, appears to be common and severe in patients with chronic hoarseness, who have laryngeal lesions suggestive of GER. The causative mechanisms are not clear. The 24-h esophageal pH monitor is useful in screening this potentially treatable problem. PMID- 2596452 TI - Treatment of Campylobacter pylori does not alter gastric acid secretion. AB - The effect of treatment of Campylobacter pylori-associated gastritis on acid secretion was studied to examine further the strong association between C. pylori and peptic diseases. Twelve symptomatic patients with non-ulcer dyspepsia and C. pylori-associated histologic gastritis had basal and pentagastrin-stimulated gastric acid analysis before and after a 14-day course of amoxicillin 250 mg qid and bismuth subsalicylate 524 mg qid. Endoscopy, antral biopsies, and symptom questionnaires were obtained at entry and at the conclusion of the study. C. pylori was identified by Warthin-Starry stain. Biopsy specimens were also graded for the severity of chronic inflammation and the presence of neutrophils in the epithelium. The treatment regimen cleared C. pylori in 10 of 12 patients. Dyspeptic symptoms improved in 10 of 12 patients, two of whom did not clear the organism, and were unchanged in the remaining two patients, both of whom cleared the bacteria. Neutrophil infiltration in the antral biopsies resolved in 10 patients, including nine with C. pylori clearance and one with persistence of the organism. The severity of the underlying chronic inflammation improved in only one of the 10 organism-free patients and one of the two persistently infected individuals. Pretreatment gastric acid analysis demonstrated hypochlorhydria in three of 12 patients, mild hyperchlorhydria in three of 12 patients, mild hyperchlorhydria in two of 12, and normal acid secretion in the remaining seven patients. Posttreatment acid studies revealed that four of 12 patients were hypochlorhydric, one of 12 had hyperchlorhydria, and seven of 12 were normochlorhydric. After treatment, there was no significant change in basal or maximal acid secretion in the 10 patients who cleared the organism. The two patients who failed to clear C. pylori had insignificant increases in acid secretion after treatment. Our data show no consistent pretreatment pattern of acid secretion in patients with C. pylori-associated gastritis. In addition, gastric acid output did not show a consistent change after treatment for C. pylori. This suggests that the association between C. pylori infection and peptic diseases does not occur via altered acid secretion. PMID- 2596453 TI - Atypical mycobacterial infection of the gastrointestinal tract in AIDS patients. AB - This paper will describe a case series of 35 AIDS patients with infection of the gastrointestinal (GI) tract with Mycobacterium avium-intracellulare (MAIC). Thirty-five homosexual men with a mean age of 35 yr and a mean duration of AIDS of 7.7 months prior to the diagnosis of MAIC were investigated to determine the extent of MAIC infection. The investigations included upper endoscopy, sigmoidoscopy, liver biopsy, bone marrow aspiration and biopsy, stool and blood cultures for MAIC, and D-xylose absorption tests. Tissue biopsy material was examined by light microscopy with the Ziehl-Neelsen stain. The duodenum was most commonly involved (30/34 men), with 65% positive on special stains and 76% positive on culture of biopsy tissue. Unusual fine white nodules, believed to be characteristic for duodenal MAIC infection, were observed in 12 men. Esophageal (two men), liver (two men), and rectal involvement (seven men) were found. In nine of 18 men (50%), the D-xylose test was abnormal. In 28 of 33 men (85%), blood cultures grew MAIC. Similarly, in 25 of 28 men (89%), bone marrow biopsies grew MAIC, and in 18 of 21 men (86%) stool samples grew MAIC. We conclude that GI tract infection with MAIC in AIDS patients is frequently associated with systemic infection with the agent. Duodenal involvement is common, and may be accompanied by a characteristic gross lesion, that of fine white nodules on the mucosa. Malabsorption, as determined by the D-xylose test, is not a universal finding, as has been reported previously. PMID- 2596454 TI - Liver biopsies in the acquired immune deficiency syndrome: influence of endemic disease and drug abuse. AB - A retrospective review of 48 liver biopsies in 34 patients with acquired immune deficiency syndrome (AIDS) and 10 patients with AIDS-related complex (ARC) was performed at Harlem Hospital Center to assess the diagnostic yield of liver biopsies in this distinct patient population. Among the patients, 93.2% were black and 32 were males, with a mean age of 36.7 yr. Intravenous drug abuse was a risk factor for AIDS in 81.8% of patients. Liver biopsies were particularly useful in patients with fever of unclear origin, which was positively correlated with the presence of granulomas (p = 0.01). Granulomas due to mycobacteria were present in 16 (33.3%) of the biopsies. Liver biopsy proved to be clinically significant in 14 of 17 patients (82.3%) with mycobacterial disease, or 29.3% of the liver biopsies. Chronic active hepatitis was present in 12 (29.2%) of the biopsies, and in all but one was due to non-A non-B hepatitis viruses. All patients with chronic active hepatitis were intravenous drug abusers or the sexual partners of intravenous drug abusers. Liver biopsy can provide important diagnostic information in AIDS patients. The pathological findings in this series reflect the high risk of exposure to tuberculosis and hepatitis in the intravenous drug abusers in Harlem. PMID- 2596455 TI - T lymphocyte activation in chronic hepatitis B infection: interleukin 2 release and its receptor expression. AB - The present study was undertaken to examine early T lymphocyte activation in chronic hepatitis B virus (HBV) carriers. Nineteen hepatitis B surface antigen positive patients (eight with liver cirrhosis and 11 with chronic hepatitis) and 18 healthy controls were studied in a period free of other infection. Mitogen stimulated cellular interleukin 2 receptor expression, soluble interleukin 2 receptor release, and interleukin 2 production were studied in peripheral blood mononuclear cells cultured for 24 h. No difference was demonstrated between the patients and healthy controls in the cellular interleukin 2 receptor expression, soluble interleukin 2 receptor release, and interleukin 2 production. Pokeweed mitogen-stimulated interleukin 2 production in lymphocytes from cirrhotic patients was significantly lower than that of the noncirrhotic patients. However, the cellular and soluble interleukin 2 receptor levels did not differ between the two groups of chronic HBV carriers. Despite the fact that it has been suggested that autoreactive T cells have a role in mediating the development of chronic liver diseases associated with HBV infection, this study fails to demonstrate a defective T lymphocyte activation in these patients. The observed reduction of interleukin 2 production from activated lymphocytes may be related to the severity of liver impairment, rather than the HBV infection itself. PMID- 2596457 TI - Questionable clinical significance of Blastocystis hominis infection. AB - In the period from January 1986 to July 1988, Blastocystic hominis was found in moderate and numerous quantities in 103 (1.6%) of 6,262 stool specimens examined in our laboratory. There was no significant association of the detection of B. hominis with travel history or symptoms. Indeed, 20 patients (36%) with moderate to heavy infections had no gastrointestinal symptoms, and three symptomatic patients did not show clinical improvement after elimination of the parasite. Reexamination of stool samples revealed that eight untreated patients had spontaneous disappearance of B. hominis. We conclude that B. hominis probably is not responsible for clinical symptoms when detected, and additional investigations should be pursued for other etiologies of the patient's symptoms. PMID- 2596456 TI - Intrahepatic expression of pre-S proteins of hepatitis B virus and its possible relation to liver cell necrosis. AB - To assess the significance of intrahepatic expression of pre-S1 and S2 proteins of hepatitis B virus (HBV) in patients with HBV infection, an indirect immunoperoxidase technique employed monoclonal antibodies to pre-S proteins was used to detect pre-S1 and -S2 proteins in 80 liver specimens. The frequency of pre-S1 and -S2 proteins was 61.3% and 51.3%, respectively, and the co-expression of pre-S and HBsAg occurred in most specimens. The preferential expression of pre S1 and -S2 in HBcAg-positive specimens suggests that pre-S proteins are associated with HBV replication. Membranous expression of both pre-S1 and -S2 is associated with inflammatory activity and liver cell necrosis. Furthermore, our results show that T cells, not NK or B cells, were the predominantly infiltrating cells in necrotic foci with pre-S expression. Almost all of these T cells may express HLA-DR antigen simultaneously; therefore, they are activated. In conjunction with these data, we conclude that, as the essential components of HBV envelope proteins, pre-S proteins may play an important role in resulting in liver cell necrosis. PMID- 2596458 TI - Acute necrotizing gastritis in a patient with peptic ulcer disease. AB - Gangrene of the stomach is a rare, often fatal disease which may be due to vascular, chemical, mechanical, or infectious etiologies. The infectious type, acute necrotizing gastritis, is thought to be a variant of phlegmonous gastritis, which has been associated with recent large intake of alcohol, "gastritis," and upper respiratory tract infections. Our patient, who had a history of peptic ulcer disease and gastric outlet obstruction, presented with abdominal pain, hypotension, and pneumomediastinum. PMID- 2596460 TI - Pancreatic tail carcinoma discovered by routine flexible sigmoidoscopy. PMID- 2596459 TI - Dilated cardiomyopathy associated with chylous ascites. AB - Chylous ascites is a well-documented sequelae of traumatic rupture of the thoracic duct and mechanical obstruction of the lymphatic system due to neoplastic, inflammatory, or congenital anomalies. Less commonly, chylous ascites results from altered hemodynamics and lymphatic flow, as seen in cirrhosis and constrictive pericarditis. Rarely, severe right-sided heart failure from a variety of causes has also resulted in chylous ascites or a protein-losing enteropathy. We report a case of chylous ascites due to dilated cardiomyopathy with autopsy findings. The pathophysiology of chylous ascites formation in right heart failure will be discussed, with a review of the literature. PMID- 2596461 TI - Fulminant liver failure and pancreatitis associated with the use of sulfamethoxazole-trimethoprim. AB - We report the case of a 26-yr-old patient with fulminant liver failure and acute hemorrhagic pancreatitis secondary to the use of trimethoprim-sulfamethoxazole (Bactrim DS). Our patient presented with skin rash and decreased C3 and C4 levels, which we believed was due to a hypersensitivity reaction secondary to the sulfonamide component (sulfamethoxazole). To our knowledge, this is the first case reported in which sulfamethoxazole-trimethoprim has been implicated as a cause of fulminant liver failure and acute hemorrhagic pancreatitis simultaneously, and emphasizes the need of discontinuing this medication as soon as there is evidence of liver and pancreatic dysfunction. PMID- 2596462 TI - Malacoplakia of the colon in association with colonic adenocarcinoma. AB - We present two cases of malacoplakia of the colon in association with adenocarcinoma. The foci of malacoplakia characteristically comprised submucosal proliferations of histiocytes and chronic inflammatory cells with the typical cytoplasmic inclusions known as Michaelis-Gutmann bodies. These foci were found, respectively, adjacent to, and in contiguity with, a well- and moderately differentiated colonic adenocarcinoma. The possible pathogenetic relationship between these two processes is discussed. PMID- 2596463 TI - Nonmalignant loculated ascites. PMID- 2596464 TI - Primary biliary cirrhosis and multiple sclerosis. PMID- 2596465 TI - Hematemesis in gastric ascariasis. PMID- 2596466 TI - Hepatitis B-associated chronic inflammatory polyradiculoneuropathy. PMID- 2596467 TI - Sucralfate enemas in the treatment of chronic postradiation proctitis. PMID- 2596469 TI - Endoscopic stenting for biliary stones after Billroth II gastrectomy. PMID- 2596468 TI - Metoclopramide-associated parkinsonism mimicking functional psychiatric illness. PMID- 2596470 TI - Primary Kaposi's sarcoma simulating hemorrhoids in a patient with acquired immune deficiency syndrome. PMID- 2596471 TI - Reassessment of treatment results in membranoproliferative glomerulonephritis, with emphasis on life-table analysis. AB - Treatment of idiopathic membranoproliferative glomerulonephritis remains an unsettled issue. The results of five randomized clinical trials have not provided convincing evidence for the effectiveness of any treatment. Follow-up periods in these trials were relatively short-term, ranging from 1 to 4 years. In three recently published long-term clinical studies of patients with membranoproliferative glomerulonephritis, 10-year cumulative survival free of renal failure improved by 20% to 35% over that described in studies published 5 to 10 years earlier. In each study, survival was estimated using life-table analysis. The survival curve in the treated group was then compared with that of a historical control group using the date of clinical onset as time zero. The survival curve in the treatment group was spuriously shifted to the right. By definition, those in the treatment groups had to survive from clinical onset to initiation of treatment, but the historical control group did not have such a constraint. The problem in this comparison is that treatments were not started in a large number of patients for years after clinical onset, resulting in a biased comparison in favor of the treatment groups. (Also, the conclusions drawn from the survival data were that the improvement related directly to various treatments that were used.) Survival was similarly improved in patients treated with dipyridamole and aspirin when survival was plotted against time after clinical onset. However, when the data were replotted and the platelet-inhibitor treated group was compared with a contemporary randomized control group, no difference in either patient survival or survival free of renal disease was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596472 TI - Glomerular effects of pregnancy in a model of glomerulonephritis in the rat. AB - These studies were designed to investigate the functional and morphologic glomerular effects of pregnancy in a model of experimentally induced glomerulonephritis (GN) in the Munich-Wistar rat. Virgin and midterm (day 12) pregnant rats were studied during the autologous phase of anti-glomerular basement membrane antibody GN and were compared with normal control virgin and pregnant rats. In this model of moderately intense GN, glomerular filtration rate (GFR) and single-nephron GFR were not different from normal controls; however, glomerular micropuncture revealed that glomerular capillary blood pressure was elevated and the glomerular capillary ultrafiltration coefficient, Kfi, was reduced in rats with GN compared with normal rats. In addition a substantial proteinuria was present, and there was morphologic evidence of a moderate and fairly uniform GN. The superimposition of pregnancy to midterm (11 to 13 days) had no effects on the proteinuria or glomerular morphology in rats with GN. Also, pregnancy did not further alter the increased glomerular blood pressure or reduced Kf that occur in this model of GN. Despite the presence of an underlying glomerular disease, the maternal kidney was able to increase renal plasma flow. When underlying mild GN is present, 11 to 13 days of pregnancy does not appear to worsen the disease in the short term. Other studies are needed to determine the long-term renal effects of repeated pregnancy when underlying GN is present. PMID- 2596473 TI - Variable efficacy of calcium carbonate tablets. AB - Orally administered calcium carbonate tablets are commonly prescribed as a calcium supplement and for their phosphate-binding effects in renal failure patients. Two cases are reported in which a commercially available brand of calcium carbonate tablets appeared to be ineffective. Formal investigation of the bioavailability of this product revealed it to have impaired disintegration and dissolution and a lack of clinical efficacy. Recommendations that will enable physicians to avoid prescribing and pharmacists to avoid dispensing ineffective calcium carbonate tablets are proposed. PMID- 2596474 TI - Adsorption of unactivated complement proteins by hemodialysis membranes. AB - Hemodialysis using polyacrylonitrile (PAN) membranes has been reported to be associated with depletion of complement in the plasma, yet the increase in plasma C3a antigen concentrations and the degree of leukopenia are modest. These observations suggest that PAN membranes may have a large propensity to adsorb native complement proteins; as a consequence, complement depletion can occur without activation. In the present study, we observed that incubation of human serum in the presence of PAN membrane resulted in a 50% loss of serum hemolytic activity of C3. When radiolabeled purified components were offered, PAN membranes were found to adsorb C3 and C5 in a dose-dependent manner. Adsorption of these proteins by PAN was more than 20 times greater than adsorption by cuprophan, cellulose acetate or Hemophan (Akzo, formerly Enka, Wuppertal, FRG) at all concentrations examined. These results suggest that depletion of complement when serum is exposed to hemodialysis membranes may result from adsorption of complement components onto the membrane surfaces and does not necessarily indicate complement activation. PMID- 2596475 TI - Recombinant human erythropoietin treatment may improve quality of life and cognitive function in chronic hemodialysis patients. AB - Medical, psychological, and social adaptation (quality of life) as well as cognitive function were studied in 15 chronic stable hemodialysis patients before the onset of treatment with recombinant human erythropoietin (r-HuEPO), 1 month after stabilization of normal hematocrit levels, and 10 to 15 months after treatment onset. After r-HuEPO treatment, subjects had significantly higher hematocrits, markedly improved energy levels, and marginally improved global health. r-HuEPO treatment was also associated with progressively decreased levels of subject mood disturbance and dialysis-related stresses. Subjects had no increased participation in paid employment and only minimally increased participation in social and leisure activities at posttreatment data points. There was no significant improvement in cognitive function after treatment. r HuEPO treatment appears to be associated with higher energy levels, significant psychological benefits, and minimal improvements in social adaptation. The effects on cognitive function merit further study. PMID- 2596476 TI - The safety and the efficacy of maintenance therapy of recombinant human erythropoietin in patients with renal insufficiency. AB - Ten anemic predialysis renal patients participated in a study to examine the long term effects of recombinant human erythropoietin (r-HuEPO) treatment. The drug was initially given intravenously three times a week for 1 to 5 months, then by subcutaneous injections three times each week for 4 to 8 months, and finally by subcutaneous injection once weekly for 3 to 18 months. The duration of follow-up ranged from 11 to 29 months. Anemia was ameliorated in all participants. Mean hematocrit increased from a basal value of 26.8% to 35.1% during the intravenous phase and to 36.7% and 34.6% during the two subcutaneous periods. Mean weekly doses of erythropoietin (EPO) were 276 units/kg during intravenous therapy and 134 and 108 units/kg in the two subcutaneous periods. The differences in the doses were significant only between the intravenous and the two subcutaneous periods. Mean erythrocyte mass increased from a baseline value of 13.6 mL/kg to 20.4 mL/kg 8 months after initiation of treatment. Mean erythrocyte survival half time was increased from 23 days before to 26 days, 8 months after r-HuEPO treatment, P less than 0.002. Mean blood pressure (mm Hg) was 105 before and 95 after treatment. Mean serum creatinine was 513 mumol/L (5.8 mg/dL) at the beginning of the study. At the time of this writing (11 to 29 months after treatment), seven patients have required dialysis treatment. There were three episodes of transient refractoriness to r-HuEPO documented during periods of infection and surgical procedures. All subjects tolerated the medication well, and no serious side effects attributable to the medication were noted. Furthermore, circulating antibodies against r-HuEPO were consistently negative. PMID- 2596477 TI - Tubulointerstitial nephritis due to vancomycin. AB - Vancomycin was used to treat a patient with Staphylococcus aureus endocarditis. After 3 weeks of therapy, the patient developed a diffuse maculopapular rash, which resolved upon stopping the drug. Rechallenge with vancomycin several days later resulted in reappearance of the rash and rapid onset of acute anuric renal failure. Renal biopsy revealed acute granulomatous interstitial nephritis. This is the first report of biopsy-proven vancomycin-induced acute interstitial nephritis. Renal function should be monitored closely in patients receiving vancomycin therapy. PMID- 2596478 TI - Rebound surges of intracranial pressure as a consequence of forced ultrafiltration used to control intracranial pressure in patients with severe hepatorenal failure. AB - Cerebral edema remains the most common immediate cause of death in patients with fulminant hepatic failure. We have used ultrafiltration as a method of controlling intracranial pressure (ICP) when other measures have failed. Two cases in which an initial decrease in ICP was followed by a marked rebound increase resulting in death are reported. PMID- 2596479 TI - Acute renal failure with glomerular thrombosis in a patient with chronic scleroderma. AB - A 48-year-old woman with a 20-year history of scleroderma presented with malignant hypertension, thrombocytopenia, and acute renal failure. Renal biopsy demonstrated vascular changes consistent with scleroderma and glomerular thrombi. Her clinical course was consistent with hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP)-like syndrome. Plasma exchange therapy was associated with an improvement in renal function and rise in platelet count. This case suggests that acute renal failure in patients with scleroderma can be associated with glomerular thrombi and may improve with plasma exchange therapy. PMID- 2596480 TI - Kidney disease in blacks initiative. PMID- 2596481 TI - Caught in the act! PMID- 2596482 TI - Minimal-change glomerulopathy associated with diclofenac: response to prednisone. PMID- 2596483 TI - Severe flank pain as the predominant symptom of IgA nephropathy. PMID- 2596484 TI - Prevalence of silicosis at death in underground coal miners. AB - This study was initiated by the National Institute for Occupational Safety and Health (NIOSH) and the Bureau of Mines (BOM) to determine the prevalence and pathological features of silicosis in coal miners. The population base was 3,365 autopsied underground miners whose records were submitted to the U.S. National Coal Workers' Autopsy Study between 1971 and 1980. This program is voluntary and covers an estimated 10% of all coal workers who die. The mean age at death of the population was 62 years, of whom 75% were current or ex-smokers at the time of death. The average work tenure was 26 years. Lung sections from all cases were reviewed and the type and severity of pneumoconiosis documented. These findings were correlated with years of mining, job history, and geographic location of mine. Classical silicotic nodules were found in 12.5% of the population. There was a significant relationship between length of underground mining and prevalence and severity of silicosis consistent with a dose-response effect. The study also showed that job category and geographic location of the mine were important determinants of silicosis prevalence and that silicosis was strongly associated with higher categories of coal workers' pneumoconiosis. PMID- 2596485 TI - Assessment of exposure to chemicals in a complex work environment. AB - Exposure information was evaluated for two large chemical manufacturing facilities and a research and development center in support of occupational health studies of employees assigned to these facilities. Methodology and rationale underlying the exposure categorization are provided, and descriptive exposure statistics are presented for a sample of 774 employees. Analysis of work patterns and exposure profiles revealed that 1) employee transfers among various production work areas did not follow a predictable pattern, 2) over 41% of the chemicals identified were present in multiple work areas, and 3) individuals exposed to one chemical of toxicologic interest were also likely to be exposed to other similarly toxic materials. The use of both work area and chemical-specific exposure measures is recommended, as each may be helpful in addressing etiologic questions regarding complex work environments. PMID- 2596486 TI - Follow-up of hearing thresholds among forge hammering workers. AB - Hearing threshold was reexamined in a group of forge hammering workers investigated 8 years ago with consideration of the age effect and of auditory symptoms. Workers were exposed to impact noise that ranged from 112 to 139 dB(A)- at an irregular rate of 20 to 50 drop/minute--and a continuous background noise that ranged from 90 to 94 dB(A). Similar to what was observed 8 years ago, the present permanent threshold shift (PTS) showed a maximum notch at the frequency of 6 kHz and considerable elevations at the frequencies of 0.25-1 kHz. The age corrected PTS and the postexposure hearing threshold were significantly higher than the corresponding previous values at the frequencies 0.25, 0.5, 1, and 8 kHz only. The rise was more evident at the low than at the high frequencies. Temporary threshold shift (TTS) values were significantly less than those 8 years ago. Contrary to the previous TTS, the present TTS were higher at low than at high frequencies. Although progression of PTS at the frequencies 0.25 and 0.5 kHz was continuous throughout the observed durations of exposure, progression at higher frequencies occurred essentially in the first 10 to 15 years of exposure. Thereafter, it followed a much slower rate. Tinnitus was significantly associated with difficulty in hearing the human voice and with elevation of PTS at all the tested frequencies, while acoustic after-image was significantly associated with increment of PTS at the frequencies 0.25-2 kHz. No relation between PTS and smoking was found. PTS at low frequencies may provide an indication of progression of hearing damage when the sensitivity at 6 and 4 kHz diminishes after prolonged years of exposure. Tinnitus and acoustic after-image are related to the auditory effect of forge hammering noise. PMID- 2596487 TI - Occupational risk of decreased plasma cholinesterase among pesticide production workers in Taiwan. AB - To determine the influence of ventilation control and work practices on the health of workers potentially exposed to organophosphate and carbamate compounds, we examined a total of 989 employees from pesticide factories in Taiwan during 1986-1987. Each employee was examined by a physician, and a blood sample was drawn for plasma cholinesterase, complete blood count, and liver and renal function tests. Forty-one employees with medical conditions that might alter the plasma cholinesterase were excluded. Results showed that 43 of 515 production employees had decreased plasma cholinesterase as compared with four of 340 non production employees. Production employees working under adequate ventilation control seemed to have a lower prevalence of decreased plasma cholinesterase than those under inadequate ventilation control, although the difference was not statistically significant (p = 0.242). There was a significant association between the level of housekeeping and work practices and the prevalence of decreased plasma cholinesterase (p = 0.022). We conclude that inadequate ventilation control and poor work practices may create a potential danger of pesticide poisoning among production employees in Taiwan and should be corrected immediately. PMID- 2596488 TI - Neurochemical effect of lead exposure: a study on catecholamine metabolism. AB - In an attempt to examine the neurochemical changes of lead exposure, a study was conducted on 106 lead workers and a control group of 25 nonexposed workers. The urinary excretion of major catecholamine metabolites, homovanillic acid (HVA), and vanillylmandellic acid (VMA) were measured. Workers exposed to lead had a mean blood lead concentration of 43.2 micrograms/100 ml, whereas the concentration for workers not exposed to lead was 12.7 micrograms/100 ml. Urinary HVA was significantly elevated in the exposed group when compared with controls (p less than 0.01). HVA was also found to be associated with an increase of lead in blood. Although not statistically significant, the VMA excretion was also noted to be moderately elevated; however, it is recognized that the present study was unable to establish a highly significant dose-response relationship between lead exposure and HVA excretion, as has been reported earlier in lead-poisoned children. PMID- 2596489 TI - Dose-excretion relationship in tetrachloroethylene-exposed workers and the effect of tetrachloroethylene co-exposure on trichloroethylene metabolism. AB - Personal monitoring of 8-hour time-weighted average intensity of exposure with diffuse samplers and analysis of shift-end urine for total trichloro-compounds (TTC) and other metabolites were conducted in two groups of workers in China, one (121 subjects) exposed to tetrachloroethylene (TETRA) alone, and the other (38 subjects) exposed to a mixture of TETRA and trichloroethylene (TRI). Urinalysis was also performed on samples from 103 non-exposed controls. A linear exposure excretion relationship could be observed in both groups of workers. Comparison of these results with those of Japanese TETRA-workers suggested the presence of ethnic difference in TETRA metabolism. Urinary metabolite levels were markedly lower in the mixed (TETRA + TRI) exposure group as compared to previous findings in a group exposed to TRI alone. The observation indicates that metabolism of TRI is suppressed by the co-exposure to TETRA in humans. PMID- 2596490 TI - Exposure-outcome relationships between organic solvent exposure and neuropsychiatric disorders: results from a Dutch case-control study. AB - In this article the material collected for a case-control study is analyzed in order to evaluate the existence of relationships between organic solvent exposure and the entitlement to disability benefits due to neuropsychiatric disorders. Questionnaires were used to collect information on 252 cases receiving compensation due to neuropsychiatric disorders and 822 controls about their occupational history and work practices related to organic solvent exposure. In order to estimate the exposure to organic solvents, three exposure indices were used: duration of exposure, painters' index, and general exposure index. Analysis showed some tendencies indicating positive exposure-outcome relationships. Furthermore, some work activities and working conditions associated with high exposure to organic solvents (e.g., poor ventilation, using paint removers) resulted in a marked increase of the likelihood for receiving disability benefits due to neuropsychiatric disorders. PMID- 2596491 TI - Occupational exposure standards in Canada: from ACGIH to? AB - The methods to control exposure to hazardous substances in Canadian workplaces have undergone several changes over the past 50 years. At first, government officials simply used good ventilation practices as a guide. Later, when the ACGIH published recommended exposure limits, a closely knit industrial hygiene community readily adopted them. Recently, the pre-eminent position of the ACGIH has come under scrutiny. As a consequence, there is a search for new bipartite or tripartite approaches toward standard setting. PMID- 2596493 TI - Diabetes and hypertension. Proceedings of a symposium. June 2, 1989, Detroit, Michigan. PMID- 2596492 TI - Oculotoxins: effects, implications, and importance in occupational health. AB - A large number of chemicals are being used in industries. The potential of many of these chemicals to cause ocular damage has been well documented. It is therefore important that proper attention be given to the prevention of visual handicap among the population exposed to industrial chemicals. The aim of the present article is to create awareness and provoke discussion among concerned health personnel and administrators. PMID- 2596494 TI - Plasma volume in resistant hypertension: guide to pathophysiology and therapy. AB - It might be expected that the tremendous increase in available antihypertensives would eliminate resistant hypertension by allowing many alternatives to its treatment. In spite of this, resistant hypertension remains a common problem due, the authors feel, to a poor understanding of the pathophysiology of this condition, particularly an understanding of whether plasma volume expansion mediates resistance to antihypertensive therapy. The authors evaluated the status of plasma volume as a major determinant of response to therapy in nine patients with resistant hypertension. Measuring plasma volume using I125 radiolabeled albumin, they found eight patients with elevated plasma volumes and one patient with a contracted plasma volume at the time of presentation with resistant hypertension. In all eight patients with plasma volume expansion, aggressive diuretic therapy allowed goal blood pressure to be achieved. The patient with plasma volume contraction achieved goal blood pressure with vasodilator therapy. Plasma volume expansion is common in resistant hypertension and it mediates resistance to therapy. Measurement of plasma volume gives the clinician important insight into the pathophysiology of resistant hypertension and increases the likelihood of successful management of the resistant hypertensive patient. PMID- 2596495 TI - An analysis of ultrafiltration during acute peritoneal dialysis in rats. AB - Transport into and from the peritoneal cavity is effected through separate membranes. Peritoneal function is the sum of the contributions of these membranes. The peritoneal dialysis membranes are defined as intestinal viscera and mesentery, parietal lining membrane, and liver and diaphragm. The present study was undertaken to determine which of these membranes participate in ultrafiltration during peritoneal dialysis. Studies were performed in rats using a hypertonic (1200 mOsm/L) dialysate solution containing 5.6% glucose, 2.8% amino acid, and electrolytes. Both intact and eviscerated rats were studied. The experiments were repeated in animals whose diaphragms were fibrotic and densely adherent to liver. Preparation of the diaphragm did not impact upon ultrafiltration. Ultrafiltration in controls (54 vs. 56 ml with and without a fibrotic diaphragm respectively) and in eviscerated groups (44 vs. 45 ml with and without a fibrotic diaphragm respectively) were not significantly different. However, controls had significantly more ultrafiltration than did eviscerated animals (p less than 0.01). The parietal viscera accounted for 56-59% of the ultrafiltration. This study demonstrates that both the intestinal viscera and parietal walls participate in ultrafiltration. PMID- 2596496 TI - Unilateral gynecomastia associated with thoracotomy following resection of carcinoma of the lung. AB - A 66-year-old man developed right painful gynecomastia following resection of a well-differentiated squamous cell carcinoma from the right upper lobe. In 1979, he had a well-differentiated squamous cell carcinoma resected from the left lower lobe. Extensive investigation did not reveal any definite indication of metastases or residual carcinoma. There was no evidence for thyroid, liver, or renal disease. His plasma testosterone was 400 ng/dl, estradiol was 43 pg/ml, LH 3.5 ng/ml, FSH 13.1 mIU/ml and HCG less than 5 mIU/ml. Since no other cause of gynecomastia was apparent , it was attributed to the right thoracotomy. PMID- 2596497 TI - A new presentation of disseminated histoplasmosis in a homosexual man with AIDS. AB - The clinical and histopathological features and the therapeutic response of a pustular eruption occurring in a homosexual man with Acquired Immune Deficiency Syndrome (AIDS) is reported. The rare cutaneous presentation consisted of mostly circumscribed, tender, tense pustules, associated with erythema, confined to the face and neck. Biopsy of these lesions revealed intracellular round to oval bodies surrounded by a clear space, consistent with Histoplasma capsulatum. Prompt resolution was observed after initiation of amphotericin B therapy. Clinicians are alerted to the occurrence of exotic presentations of this entity and emphasis is given to the need for skin biopsy and culture to avoid delay in diagnosis and failure to initiate appropriate therapy. PMID- 2596499 TI - Lissencephaly, abnormal lymph nodes, and T-cell deficiency in one patient. AB - We report on a child with lissencephaly type I, abnormal lymph nodes, and immunodeficiency, associated with recurrent infections, autoimmune disease, spastic tetraplegia, and psychomotor retardation. Diagnostic measures included cranial computer tomography (CT) and magnetic resonance imaging (MRI) scanning, several in vivo and in vitro immunological tests, and histology of skin, lymph nodes, and liver including electron microscopy and immunohistology. Despite medical supervision, the child died at age 4 years. A common pathogenetic mechanism of defective migration of neurons and the dysmaturation of lymph nodes is most probable. The T-cell deficiency may represent a common defect of the development of both neuronal and lymphatic tissue, as the six-layered cerebral cortex and the B-cell areas in lymph nodes develop at about the same gestational age. A common defect could also be assumed involving genetically determined cell surface proteins. PMID- 2596498 TI - Toxic delirium in a patient taking amantadine and trimethoprim-sulfamethoxazole. AB - Acute mental confusion occurred in a patient on a stable dose of amantadine after he was started on trimethoprim-sulfamethoxazole. Discontinuation of the drugs led to rapid improvement. Studies in a rat model of organic cation secretion demonstrate that both amantadine and trimethoprim, but not sulfamethoxazole, inhibit the renal secretion of the organic cation procainamide. This case may represent an amantadine-trimethoprim interaction. PMID- 2596500 TI - Congenital shortness of the costocoracoid ligament. AB - We report a large kindred in which individuals presented with fixation of the scapula to the first rib by a congenitally short costocoracoid ligament. Cosmetic deformity with rounding of the shoulder and loss of the anterior clavicular contour was the main concern of the affected individuals. Movements requiring rotation or retraction of the scapula were limited, although this did not interfere with normal activities. Surgical treatment consists of excision of the costocoracoid ligament and resulted in some correction of the cosmetic deformity. The pedigree supports an autosomal dominant mode of inheritance with variable expression. The abnormality results in a pectoral girdle which is reminiscent of that seen in the monotremes. PMID- 2596501 TI - Postaxial acrofacial dysostosis: report of a Brazilian patient. AB - We report on a Brazilian child with postaxial acrofacial dysostosis (AFD)-type Genee-Wiedemann. Clinical and genetic aspects of the postaxial acrofacial dysostoses are discussed. PMID- 2596502 TI - Atypical postaxial acrofacial dysostosis (AFD): diabetic embryopathy or a new AFD syndrome? AB - We report on a Brazilian girl, born to a diabetic mother, and presenting with atypical pre/postaxial acrofacial dysostosis, nosologically related to the Genee Wiedemann syndrome. Clinical and genetic aspects of this acrofacial dysostosis and its relationship to diabetic embryopathy are discussed. PMID- 2596503 TI - A case of de novo i(12p) with 12q whole-arm translocation mosaicism. AB - We report a dup(12p) due to a de novo i(12p) in a girl with mosaicism for 12q whole-arm translocations onto 7p, 7q, and 11q terminal regions. The dup(12p) syndrome was confirmed by clinical, cytogenetic, and LDH-dosage studies. PMID- 2596504 TI - Nocturnal rhythm of growth hormone in Duchenne patients: effect of different doses of mazindol and/or cyproheptadine. AB - Human growth hormone (hGH) inhibition may be beneficial for Duchenne muscular dystrophy (DMD) patients and slow the rate of progression of the disease. The purpose of the present investigation was 1) to assess, before any therapeutic trial, the natural growth hormone (GH) rhythm during physiological sleep in DMD patients and in normal control boys of comparable age; 2) to evaluate the effect of different doses of two potential GH inhibitors on nocturnal GH secretion in DMD patients receiving mazindol (1-4 mg), cyproheptadine (4-8 mg), or both drugs. The results from the present investigation showed 1) wide variability in nocturnal GH secretion before medication; 2) no correlation between nocturnal GH concentration and height, age, bone age, L-dopa provocative test, or Tanner staging; and 3) no consistent effect on GH release after mazindol, cyproheptadine therapy, or combined therapy. PMID- 2596505 TI - Cardio-facio-cutaneous (CFC) syndrome: report of a new patient. AB - We describe a girl with the cardio-facio-cutaneous (CFC) syndrome. She presented most of the characteristics of the new multiple congenital anomalies/mental retardation (MCA/MR) syndrome: unusual facial appearance and ectodermal symptoms, that is, abnormal hair and skin, ventricular septum defect, relative macrocephaly with large ventricles and cortical "atrophy," submucous cleft palate, and umbilical hernia. Her twin brother died shortly after birth and may have had the same malformation syndrome. PMID- 2596506 TI - A case of cardio-facio-cutaneous syndrome. AB - A 6-yr-old girl is described who presented with failure to thrive at age 3 months and was found to have mental retardation, growth retardation, disproportionately large head, distinctive face, abnormal hair, eczema, heart defect, splenomegaly, and multiple hemangiomata. She is thought to have the cardio-facio-cutaneous syndrome and to be the first such case identified in Britain. PMID- 2596507 TI - CFC syndrome: report on three additional cases. AB - We describe three patients, originating from three different Italian localities, affected by the cardio-facio-cutaneous (CFC) syndrome. In addition to a varying degree of mental retardation, these patients present characteristics consisting of a peculiar face with bitemporal frontal constriction and other anomalies involving the eyes, nose, ears, hair, skin, and heart that are consistent with this diagnosis. PMID- 2596508 TI - A new autosomal recessive disorder resembling Weaver syndrome. AB - Most reported cases of Weaver syndrome are sporadic, and the mode of inheritance is still unclear. We describe two (male and female) sibs born to consanguineous Bedouin parents with manifestations resembling Weaver syndrome. Both sibs had accelerated growth of prenatal onset, hypotonia, psychomotor retardation, excess loose skin, peculiar craniofacial and acral anomalies, dental dysplasia and/or serrated gums, joint laxity, and hoarse low-pitched cry. One of them had an accelerated harmonic skeletal maturation. Differentiating features from Weaver syndrome are discussed, and autosomal recessive inheritance is suggested. PMID- 2596509 TI - Dandy-Walker malformation with postaxial polydactyly: a new syndrome? AB - We report on two sibs with Dandy-Walker malformation and tetramelic postaxial polydactyly. We conclude that this is a new autosomal recessive syndrome. PMID- 2596510 TI - Microdeletion in the X-chromosome and prenatal diagnosis in a family with Norrie disease. AB - We have studied a three-generation family in which Norrie disease is segregating and have performed prenatal diagnosis on the fetus of an obligatory carrier. Deletions at loci DXS7 and DXS77 defined by probes L1.28, L1.28-p59, and pX59 were detected in the affected male. DNA studies of chorionic villus biopsy material indicated that the male fetus had inherited the normal allele from the carrier mother. This prediction was confirmed on eye examination at age 5 months. PMID- 2596511 TI - Three additional cases of the congenital hypothalamic "hamartoblastoma" (Pallister-Hall) syndrome. AB - The cause of this syndrome remains unknown. Epidemiologic studies should be done by experts. The first two cases above gave a "muddy" history for possible teratogens--a "recall bias"--one of a vaginal foam spermicide, one of exposure over several days to a heavy residue of aviation diesel fuel exhaust. We do not think these are pertinent but they do point to the problem of getting a meaningful history. In addressing this problem (in a letter of 5/27/82) R.J. Berry, M.D., medical epidemiologist, Centers for Disease Control, Atlanta, Georgia, wrote "... a designed study providing standardized interview forms with controls could be designed if cases continue to appear." Since this seems to be the case, perhaps this approach should be embraced. A teratogen(s) appears to be a good bet since the condition was recognized suddenly with the first Montana case in February, 1978. Even though no record has been found in the files of the Armed Forces Institute of Pathology, Children's Hospital Automated Medical Programs (CHAMP), Montreal or Wisconsin and one or two other places, it might be worthwhile to look back at all cases of imperforate anus which have come to autopsy for possible associated CNS lesions. We may be deluding ourselves in considering the condition as "new." Chromosomes were usually studied in lymphocytes, once on the tumor and once or twice on marrow. It might be well to do more than one tissue in all new cases. Once again there appears to be no "obligatory" finding for any one syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596512 TI - Waardenburg syndrome type I in a child with de novo inversion (2)(q35q37.3). AB - We report on a child with Waardenburg syndrome type I and a paracentric inversion of chromosome 2. This 20 month-old boy has dystopia canthorum, sensorineural deafness, heterochromia iridis, partially albinotic ocular fundi, and partial leukodermia. He does not have mental retardation or any skeletal abnormalities. Family history was unremarkable. Cytogenetic studies demonstrated that the patient has a paracentric inversion (2)(q35q37.3); his parents have normal chromosomes. These findings suggest that the locus of the gene for Waardenburg syndrome type I may be at 2q35 or 2q37.3. PMID- 2596513 TI - Growth and development in thanatophoric dysplasia. AB - Two cases of prolonged survival of thanatophoric dysplasia are presented, in which ventilatory support was initiated in the neonatal period because of respiratory distress. Both patients required a ventriculoperitoneal shunt for hydrocephalus and had decompression of the posterior fossa. The history of each patient has been characterized by profound developmental delay and dramatic growth failure. PMID- 2596514 TI - Longitudinal IQ changes in fragile X males. AB - Previous studies have reported a drop of IQ in males with Martin-Bell or fragile X syndrome during childhood and adolescence. It is uncertain when and why this drop occurs and whether it affects all fragile X males. We have analyzed longitudinal IQ data on all 24 fragile X males who have been followed for at least 2 years through the Child Development Unit in Denver and who have been evaluated with a Stanford-Binet Form L-M assessment. A significant drop in IQ occurred for the group as a whole, but an individual z analysis demonstrated that only 7 of 24 had a significant decline in IQ. Visual inspection demonstrates an initial decline in IQ beginning in middle childhood and continuing through adolescence. We postulate that this drop occurs because of relatively greater weaknesses with abstract reasoning and higher symbolic language skills that are stressed in the cognitive testing of later childhood and adolescence. PMID- 2596515 TI - Autosomal recessive form of whistling face syndrome in sibs. AB - Two sibs with the whistling face syndrome, born to unaffected parents, are presented. They had the full facial and limb manifestations typical of this disorder, for which there is evidence of autosomal dominant inheritance. The existence of an autosomal recessive form of this syndrome has been suspected previously on the basis of a limited number of observations. Our study substantiates genetic heterogeneity of this condition and suggests that the autosomal recessive form could be even less rare than is generally considered. PMID- 2596516 TI - Dominantly inherited syndromic blepharophimosis. PMID- 2596517 TI - Child with deletion of 4q and duplication of 1q. PMID- 2596518 TI - Defective lysosomal release of vitamin B12 (cb1F): a hereditary cobalamin metabolic disorder associated with sudden death. AB - Here we report on a girl who presented with failure to thrive, developmental delay, minor facial anomalies, stomatitis, skin rashes, macrocytosis, mild homocystinemia(uria), and methylmalonic acidemia(uria). Fibroblast studies showed abnormal intracellular cobalamin (vitamin B12) metabolism. Reduced incorporation of 14C from [14C] propionate and [14C] methyltetrahydrofolate into TCA precipitable macromolecules reflected decreased synthesis of adenosylcobalamin and methylcobalamin respectively. The diagnosis of cb1F mutation was established by demonstrating the accumulation of unmetabolized free cyanocobalamin in fibroblasts and by lack of genetic complementation with fibroblasts from the only other known cb1F patient. The defect is in the lysosomal release of endocytosed cobalamin. Administration of hydroxocobalamin resulted in clinical and biochemical improvement but sudden death occurred at age 5 months. The absence of brain pathological changes suggests that early treatment may prevent the neurological complications in cobalamin cofactor deficiency. PMID- 2596519 TI - Ambiguous genitalia associated with skeletal abnormalities, cutis laxa, craniostenosis, psychomotor retardation, and facial abnormalities (SCARF syndrome). AB - We describe 2 male maternal first cousins, 7 years and 7 months old, with a previously unreported pattern of malformations including lax skin, joint hyperextensibility, umbilical and inguinal herniae, craniosynostosis, pectus carinatum, several abnormally shaped vertebrae, enamel hypoplasia and hypocalcification of the teeth, facial abnormalities and wide webbed neck, ambiguous genitalia, multiple nodular liver tumors, and mild psychomotor retardation. The occurrence of 2 male children related through their mothers suggests the possibility of X-linked recessive inheritance. It is proposed to call this disorder the SCARF syndrome (skeletal abnormalities, cutis laxa, craniostenosis, ambiguous genitalia, retardation, facial abnormalities). PMID- 2596520 TI - Multiple malformations and exposure to therapeutic ultrasound during organogenesis. AB - We present a case of sacral agenesis, microcephaly, and developmental delay. The pregnancy with this child was complicated by left psoas bursitis that was treated by 18 applications of ultrasound between days 6 and 29 of gestation. PMID- 2596521 TI - Chromosome abnormalities in selected newborn infants with malformations in Brazil. AB - Between 1982 and 1985, 109 infants were referred for cytogenetic examination out of a population of 73,192 liveborn infants from eight maternity hospitals surveyed by the ECLAMC/MONITOR program. Thirty-one of the children had a chromosome abnormality different from trisomy 21. Considering the total population surveyed, trisomy 18 was detected in 1:6,099; trisomy 13 was seen in 1:24,397 and unbalanced rearrangements were found in 1:7,319 infants. Those rates were not significantly different from the expected ones, as compared to previous cytogenetic surveys of consecutive births. We concluded that most chromosome abnormalities associated with congenital malformations can be detected at low cost, provided there is a high accuracy of clinical examination and referral criteria, as well as close cooperation between pediatricians and geneticists. PMID- 2596522 TI - Infantile hemangioendothelioma of the liver in patient with interstitial deletion of chromosome 6q: report of an autopsy case. AB - Here we report an infantile hemangioendothelioma of the liver that developed in a 6 month-old boy with an interstitial deletion of chromosome 6q. His clinical manifestations included developmental delay, feeding problems, and multiple anomalies including microcephaly, hypertelorism, apparently low set abnormal ears, prominent nasal bridge, cubitus valgus, overwrapping of fingers, cryptorchidism, and micropenis. He died abruptly at age 27 weeks from a perforating duodenal ulcer. Autopsy demonstrated atrial septal defect, microencephaly, and thymic atrophy. A solitary small tumor was found in the liver and diagnosed histologically as the infantile hemangioendothelioma, type 1. This is the first report of a del(6)q with infantile hemangioendothelioma. PMID- 2596523 TI - Trisomy 18 at age 21 years. AB - Here we report on a woman with non-mosaic trisomy 18, who is now 21 years old. She has the characteristic face of older trisomy 18 survivors, marked kyphoscoliosis, spastic quadriplegia with contractures, and profound mental retardation. She has pyorrhea with loss of three canine teeth. At 20.5 years, she had her first menstrual cycle with development of secondary sexual characteristics. PMID- 2596524 TI - Expanded phenotype and ethnicity in Setleis syndrome. AB - Setleis syndrome, an autosomal recessive disorder characterized by "coarse" face, temporal cutis aplasia, double upper eyelashes, absent lower eyelashes, chronic conjunctivitis, and prominent thick lips, was reported previously in 8 Puerto Rican children. We report on 3 unrelated children (one mentally retarded) with Setleis syndrome who are not of Puerto Rican descent. Two of our patients had imperforate anus, which has not previously been reported. The evolution of the phenotype over time is illustrated. PMID- 2596525 TI - Apparent Smith-Lemli-Opitz syndrome and Miller-Dieker syndrome in a family with segregating translocation t(7;17)(q34;p13.1). AB - We describe a family in which one male infant presented with Miller-Dieker syndrome and four male relatives had a phenotype similar to the Smith-Lemli-Opitz (SLO) syndrome. High resolution cytogenetic analysis on the child with Miller Dieker syndrome showed 46,XY,-17,+der17t(7;17)(q34:p13.1). Paternal chromosomes showed a balanced translocation: 46,XY,t(7;17)(q34:p13.1). The paternal grandmother had a history of multiple miscarriages, and a paternal uncle had two sons who died neonatally. Chromosomes on these children and their father had originally been reported as normal. There was also a paternal cousin to the father of the propositus who had had two sons with similar clinical findings. A diagnosis of SLO syndrome was considered. Image enhancement techniques on previous suboptimal preparations on these four children documented the subtle unbalanced translocation 46,XY,-7,+der7t(7;17)(q34:p13.1). Subsequent high resolution analysis on one of these four children who was still living confirmed this chromosome constitution. It is postulated that these apparent SLO cases may represent a contiguous gene syndrome in which SLO or a separate entity closely mimicking the syndrome in included. PMID- 2596526 TI - Esterase D assay in Brazilian retinoblastoma families. AB - The gene related to retinoblastoma (Rb gene) can be considered a model human tumor suppressor gene and was assigned to band 13q14, together with the esterase D (ESD) gene. We studied the ESD activity and phenotype in 40 retinoblastoma patients, 50 unaffected relatives, and 85 nonrelated healthy control individuals. ESD activity from patients is significantly different from that of relatives and control individuals, but there was no significant difference between ESD activity from unaffected relatives and control individuals. Twelve and one-half percent of patients and 4.2% of unaffected relatives with ESD1 phenotype showed a low ESD level. The results showed the importance of ESD studies in all retinoblastoma patients and their relatives. PMID- 2596528 TI - Chondrodysplasia, situs inversus totalis, cleft epiglottis and larynx, hexadactyly of hands and feet, pancreatic cystic dysplasia, renal dysplasia/absence, micropenis and ambiguous genitalia, imperforate anus. PMID- 2596527 TI - Re-evaluation of new X-linked syndrome for evidence of CHARGE syndrome or association. AB - Previously, we reported on a family with a new syndrome of cleft palate, coloboma, hypospadias, deafness, short stature, and radial synostosis. This family has been cited in several reports as an example of familial CHARGE syndrome. We do not think that the patients in this family have the Charge syndrome or association. Therefore, we decided to do a follow-up study on this family to assess the subsequent development of the patients and to determine if they have the CHARGE syndrome. We conclude that our patients do not have familial CHARGE syndrome. PMID- 2596529 TI - Hypothesis: homozygosity in Tourette syndrome. AB - We review evidence suggesting that many individuals with Tourette syndrome (TS) may be homozygous for a "Tourette syndrome" gene. This is based on experience with pedigrees on 1,200 TS families, comparison of the occurrence of tics or associated behaviors such as obsessive-compulsive behavior, panic attacks, attention deficit hyperactivity disorder, and/or severe alcohol or drug abuse, on both the maternal and paternal side in 170 TS families compared to control families, biochemical studies of blood serotonin and tryptophan levels, and other evidence. These observations suggest the inheritance in TS may be best described as semi-dominant, semi-recessive. Some of the implications of this proposal are discussed. PMID- 2596530 TI - Apparent Fryns syndrome in a boy with a tandem duplication of 1q24-31.2. AB - We report on a newborn boy with manifestations of Fryns syndrome who also had a mosaic tandem duplication of chromosome 1q24-31.2. The child had a diaphragmatic hernia, cleft palate, hypoplastic and absent digits, micrognathia, long philtrum, thin upper lip, and anteverted nose. The baby died at age 5 hours. An autopsy demonstrated absent right middle lobe of the lung, bilateral renal cysts, hypoplastic renal arteries, urethral stricture, hydronephrosis, and aortic coarctation. The brain was abnormal with absent olfactory tracts and cerebral and cerebellar heterotopias. This is the first report of a chromosome anomaly in a child with Fryns phenotype. It suggests that the gene for Fryns syndrome may be located in the region 1q24-31.2. PMID- 2596531 TI - Genetic hemochromatosis: distribution analysis of six laboratory measures of iron metabolism. AB - Six laboratory measures of iron metabolism were studied in a control sample, and a family sample was ascertained on the basis of probands with clinically diagnosed genetic hemochromatosis. The respective distribution of each variable evidenced a mixture of components, presumably arising from the segregation of an HLA-linked locus for hemochromatosis. There were significant differences in the distributional characteristics with respect to sex and genotype-specific variances. These aspects of the data have important implications for subsequent segregation and linkage analyses, which traditionally assume homoscedasticity and homogeneity of the genetic effect. PMID- 2596532 TI - X-linked cataract and X-linked microphthalmos: how many deletion families? PMID- 2596533 TI - Acral-genital anomalies combined with ear anomalies. PMID- 2596534 TI - Intellectual competence in a girl with Langer-Giedion syndrome (tricho-rhino phalangeal syndrome type II) PMID- 2596535 TI - Infection of hemodialysis catheters: incidence and mechanisms. AB - Fifty-three consecutive subclavian or jugular hemodialysis catheters inserted into 41 patients were prospectively studied over a period of 8 months in order to determine the incidence of infection and its mechanisms. The intravascular, intradermal and the Y catheter segments as well as both connections were cultured using a quantitative technique for the intraluminal surface. In addition, the intravascular and intradermal portions of the catheter were cultured using a semiquantitative technique for the external surface. Skin smears of the catheter entry site were also cultured, and blood cultures were similarly obtained if fewer developed. Twenty-nine of the 53 catheters (55%) were significantly colonized by one (19 cases) or more (10 cases) microorganisms. The source of the colonizing microorganisms was the skin in 17 cases (58%), intraluminal in 5 (17%), both routes in 5 (17%) and others in 2 (6.8%). Staphylococcus epidermidis (22 cases) and Staphylococcus aureus (4 cases) were the bacteria most frequently isolated. Nine of the 53 catheterizations (17%) were complicated by catheter related septicemia due to S. aureus in 4 cases, S. epidermidis in 3 cases, Streptococcus faecalis in 1 and Proteus vulgaris in 1. Catheter-related bacteremia contributed to a patient's death in 1 case. Suppurative local infections of the catheter entry site developed in 3 cases, 2 of them with septicemia. We conclude that the rate of infection due to subclavian or jugular hemodialysis catheters is very high and that the skin is the most frequent origin of the microorganisms. PMID- 2596536 TI - Comparative acute effects of aspirin, diflunisal, ibuprofen and indomethacin on renal function in healthy man. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, suppress renal prostaglandins and markedly reduce renal perfusion and diuretic response in some renal disorders. Mild renal impairment may occur in healthy subjects. Pharmacodynamic characteristics of certain NSAIDs, such as the nonacetylated salicylates, suggest that they may have less deleterious renal effects. We compared the renal effects of standard therapeutic doses of indomethacin, ibuprofen, aspirin, and the nonacetylated salicylate, diflunisal, in 6 healthy supine volunteers. Only indomethacin significantly reduced creatinine clearance (by 13%) and renal plasma flow (by 23%; p less than 0.05). Indomethacin also tended to reduce furosemide-induced diuresis and natriuresis, and this effect was significantly greater than with diflunisal (p less than 0.05). Serum thromboxane, a reflection of platelet cyclo-oxygenase activity, was reduced by 99% with aspirin, ibuprofen and indomethacin, but by only 78% with diflunisal. Nonacetylated salicylates may be the preferred drugs, at least in short-term usage, when it is necessary to minimize the effects of NSAIDs on platelet or kidney function. PMID- 2596537 TI - Familial distal renal tubular acidosis with neurosensory deafness: early nephrocalcinosis. AB - Nephrocalcinosis was observed in 3 children of one family with distal renal tubular acidosis (dRTA). At presentation, all 3 patients had failure to thrive, rickets, hyperchloremic metabolic acidosis, hypokalemia, hypophosphatemia and hypercalciuria. At a later age, sensorineural hearing impairment was detected. Nephrocalcinosis was diagnosed in the index case at the age of 5 years, when a plain abdominal roentgenogram was first made; in the younger brother and sister, nephrocalcinosis was detected earlier at the age of 4 months and 5 weeks, respectively. All 3 patients required large doses of alkali (7.5-9.5 mEq/kg body weight/day) during infancy and early childhood to correct the acidosis and to prevent progression of the nephrocalcinosis. Contrary to the current notion that in children with dRTA, nephrocalcinosis is observed only after the age of 3 years, it appears that in some instances nephrocalcinosis may develop in early infancy. The occurrence of nephrocalcinosis at a very young age may be a manifestation of a severe genetically transmitted variant of dRTA and emphasizes the need for early diagnosis and optimal treatment of these patients from the first days of life. PMID- 2596538 TI - Quiz of the month. PMID- 2596539 TI - Interleukin-1 production by lipopolysaccharide-stimulated glomeruli from rats with nephrotoxic serum nephritis. AB - The objective of the present work was to characterize some aspects of interleukin 1 (IL-1) production by nephritic glomeruli after stimulation with bacterial lipopolysaccharide (LPS). Freshly isolated glomeruli from rats with an accelerated autologous form of nephrotoxic serum nephritis (NTSN) were incubated for 24 h in the presence of LPS. The modified NTSN was produced by an intravenous injection of nephrotoxic serum (NTS) into the rats which had been previously immunized with rabbit IgG and Freund's complete adjuvant. The glomerular cultures of the NTSN rats were found to release significantly increased amounts of IL-1 after LPS stimulation when compared to the values obtained with normal controls and the other control group, consisting of preimmunized rats (rabbit IgG), then given normal rabbit globulin instead of NTS. To block the effect of prostaglandins on the IL-1 assay, we cultured the glomeruli with the addition of indomethacin and assayed IL-1 activity in the culture supernatants. The use of indomethacin resulted in a further increase in IL-1 production. The administration of a rabbit anti-rat macrophage serum reduced the production of IL 1 activity in the NTSN rats. Our findings support the notion that at least in NTSN rats activated macrophages are present and probably account for their increased IL-1 activity. This description of IL-1 activity produced by LPS stimulated nephritic glomeruli may introduce a new element to the early events leading to glomerular inflammation. PMID- 2596540 TI - A case of acute tubulointerstitial nephritis and uveitis syndrome with a dramatic response to corticosteroid therapy. AB - A 23-year-old female with acute renal failure associated with acute tubulointerstitial nephritis and uveitis is reported. Renal tubular acidosis and inflammatory reactions consisting of markedly increased erythrocyte sedimentation rate and high serum immunoglobulin levels were seen on admission. Light microscopy revealed infiltration of mononuclear cells in the interstitium. Immunofluorescence of renal tissues was negative in staining for immunoglobulins, fibrinogen, and complement components. Bone marrow specimens did not show any granulomatous lesions. The etiology of this tubulointerstitial nephritis and uveitis syndrome was not clear. Immunological evaluation showed a slight decrease of the OKT4/OKT8 ratio in the peripheral blood. OKT8- and OKM1-positive cells had infiltrated diffusely into the renal interstitium. Acute tubulointerstitial nephritis and uveitis responded dramatically to steroid therapy. It was suggested that immunological factors might correlate with the onset and/or development of this syndrome. It is indicated that high-dose steroid therapy might be useful for patients with acute interstitial nephritis and uveitis. PMID- 2596541 TI - Successful treatment of massive hemorrhage after percutaneous renal biopsy with transcatheter arterial embolization. PMID- 2596542 TI - Visual field damage in normal-tension and high-tension glaucoma. AB - We studied the ocular characteristics of 40 pairs of normal-tension and high tension glaucoma patients who matched closely for the extent of field damage, pupil size, and visual acuity. To determine if there were differences in visual field damage between patients with normal-tension and high-tension glaucoma, we studied characteristics of the areas of the patients' visual fields that were undisturbed. We computed the number of normal locations, the number of clustered normal locations, and the size of the largest cluster of normal locations. The results showed that for an equivalent extent of damage, the individuals in the normal-tension group had greater areas with normal sensitivity, hence more localized damage. A comparison of the patient data to control data showed that paired differences were larger when the normal-tension member of a pair had a larger value in any of the parameters. The results support the hypothesis that glaucoma patients with lower intraocular pressures have more localized damage and those with higher intraocular pressures have more diffuse damage. PMID- 2596543 TI - The influence of decreased retinal illumination on automated perimetric threshold measurements. AB - Decreased retinal illumination (such as can be caused by pupillary constriction or light absorption by ocular media opacities) was simulated with a randomly ordered series of neutral density filters in front of the right eyes of five subjects with dilated pupils. Threshold measurements were performed on Humphrey and Octopus perimeters at 0, 5, 10, 15, 20, and 25 degrees nasally along the 180 degree meridian. A 0.6-log unit neutral density filter, which reduces retinal illumination the equivalent of halving the pupillary diameter, decreased the mean Humphrey thresholds by 1.1 +/- 0.8 decibels (dB) (mean +/- standard deviation) and the mean Octopus thresholds by 1.7 +/- 1.4 dB. Statistically significant (P less than or equal to .05, Dunnett's test) threshold depressions were observed at all eccentricities with a 1.5-log unit neutral density filter on the Humphrey perimeter (-4.5 +/- 0.7 dB) and with a 1.0-log unit neutral density filter on the Octopus perimeter (-3.5 +/- 1.0 dB). PMID- 2596544 TI - Ocular Lyme borreliosis. AB - In six patients with ocular Lyme borreliosis, bilateral granulomatous iridocyclitis and vitritis were present in five. One of these five also had bilateral optic neuritis. Another patient developed combined trochlear and facial nerve palsies. A syndrome resembling pars planitis with atypical features such as granulomatous keratic precipitates and posterior synechiae should prompt a search for Lyme borreliosis. Topical corticosteroid therapy is necessary to prevent complications of anterior segment inflammation caused by Lyme uveitis, but the benefit of systemic and periocular corticosteroids is uncertain. Oral antibiotics may be effective in treating early stages of ocular Lyme borreliosis. In later stages, intravenous antibiotic therapy is indicated. PMID- 2596545 TI - Adherence of Acanthamoeba castellanii cysts and trophozoites to unworn soft contact lenses. AB - Contact lens-related Acanthamoeba keratitis has been associated with the use of soft contact lenses and homemade saline solutions. We studied the adherence of Acanthamoeba to unworn extended-wear soft contact lenses on a human corneal isolate of Acanthamoeba castellanii suspended in normal saline (cysts, 6.3 x 10(5)/ml; trophozoites, 3.6 x 10(5)/ml). Unworn hydrogel contact lenses (polymacon, water content 38.6%; 50 lenses, 400 lens segments) were exposed to A. castellanii cysts or trophozoites with or without stirring. After exposure for zero to seven hours, soft contact lenses were or were not washed, and the A. castellanii adherence was determined with a standardized light-microscopy technique (40 fields, ten lens segments for each count) and with scanning electron microscopy. Both cysts and trophozoites adhered to the unworn soft contact lenses. Trophozoites showed acanthopodia, lobopodia, and filopodia. This study indicates that both A. castellanii cysts and trophozoites can firmly adhere to unworn soft contact lens. Such adherence may play a role in the pathogenesis of soft contact lens-related Acanthamoeba keratitis. PMID- 2596546 TI - Massive suprachoroidal hemorrhage in penetrating keratoplasty. AB - We studied the frequency of massive suprachoroidal hemorrhage during and after penetrating keratoplasty. Nine cases of intraoperative or immediately postoperative massive suprachoroidal hemorrhage were identified in 830 consecutive patients (1.08%) undergoing penetrating keratoplasties at the Manhattan Eye, Ear, and Throat Hospital over a 2 1/2-year period. Six of the nine patients had atherosclerotic disease or hypertension, six of nine patients had glaucoma, and eight of nine patients had undergone previous intraocular surgery. Surgery was performed under general anesthesia in 714 patients, and four of these patients (0.56%) suffered hemorrhages. Five of 116 (4.3%) local anesthesia patients experienced expulsive choroidal hemorrhage. The increased resistance to venous outflow associated with retrobulbar anesthetic injection may significantly contribute to the risk of massive suprachoroidal hemorrhage. PMID- 2596547 TI - Refractive complications of cataract surgery after radial keratotomy. AB - Four patients underwent cataract extraction with posterior chamber lens implantation several years after radial keratotomy. All four patients experienced an initial hyperopic shift caused by an early postoperative corneal flattening of greater than or equal to 1 diopter. This flattening partially regressed, leaving the patients with a mean of 0.42 diopter of persistent corneal flattening. We found the Binkhorst and the Holladay intraocular lens calculation formulas to be more accurate than the SRK II for these patients. Corneal curvature measured with the keratometer was less accurate for intraocular lens calculations than was a value derived by subtracting the refractive change induced by the radial keratotomy from the patients' keratometric measurements obtained before radial keratotomy. PMID- 2596548 TI - The risk of fellow eye visual loss with unilateral retinal pigment epithelial tears. AB - To identify the magnitude of risk of fellow-eye visual loss, we reviewed the records of 43 patients with unilateral central visual loss caused by a tear of detached retinal pigment epithelium seen in our institution over a period of one to 13 years. Loss of vision because of complications of age-related macular disease occurred in 16 of 43 patients (37%) in the first year, seven of 23 patients (30%) in the second year, and eight of 16 patients (50%) in the third year. An additional five patients lost visual acuity between the third and eighth years of follow-up. The cumulative risk of loss of visual acuity was 37% in one year, 59% in two years, and 80% in three years. Visual loss occurred in 29 of the 36 eyes as a result of a complication of retinal pigment epithelial detachment. The magnitude of risk to the fellow eye was greater than has been documented in unselected age-related macular degeneration. PMID- 2596549 TI - Peripapillary (pericentral) pigmentary retinal degeneration. AB - Three patients with peripapillary (pericentral) pigmentary retinal degeneration described in 1978 were examined over a follow-up period of nine to 13 years. There was no extension of the geographic pigmentary abnormalities. The affected areas worsened as evidenced by an increase in pigment abnormalities, focal choroidal atrophy as seen on fluorescein angiography, and a diminution of the electroretinographic responses. One patient had increasing disabling symptoms of nyctalopia and poor peripheral and central vision, whereas the other two patients remained asymptomatic with excellent central vision. PMID- 2596550 TI - Ocular abnormalities in patients with beta thalassemia. AB - We examined 29 patients with homozygous beta thalassemia. The mean age of the patients was 15.6 +/- 8.9 years. Twelve patients (mean age, 02.0 +/- 10.4 years) had one or more ocular abnormalities. Five patients had degeneration of the retinal pigment epithelium, one had lens opacities, two had lens opacities and degeneration of the retinal pigment epithelium, one had vascular abnormalities and degeneration of the retinal pigment epithelium, one had angioid streaks, lens opacities, and degeneration of the retinal pigment epithelium, and two had angioid streaks and degeneration of the retinal pigment epithelium. These abnormalities were observed in patients with both forms of beta thalassemia, major and intermedia. The frequency of the ocular abnormalities increased with age. The youngest patient with an ocular abnormality was 6 1/2 years old. There was no correlation between the abnormalities observed and the serum ferritin level, the mean hematocrit value, and the dose of deferoxamine given to the patients. PMID- 2596551 TI - A periosteal-temporalis fascia pedicle flap for repairing impending ocular perforations and extruding keratoprostheses. AB - We repaired four eyes in four patients with impending perforation using a vascular periosteal-temporalis fascia pedicle flap continuous to the periorbita of the orbital wall. Two eyes with extruding keratoprostheses, one eye with severe ocular surface dysfunction and a perforated, infected keratoplasty, and one eye with scleral ectasia were successfully reconstructed. Excellent visual acuity (20/25) was attained in one eye and functional visual acuity (20/100) was maintained in another. Structural integrity was maintained in all eyes. A vascularized flap was an excellent source of tissue for reconstructing eyes with impending perforation and scleral melting. PMID- 2596552 TI - Ocular adverse reactions associated with adriamycin (doxorubicin). AB - To assess the ocular safety of doxorubicin, we reviewed doxorubicin-associated ocular adverse reactions reported to Adria Laboratories or published in the clinical literature. Conjunctivitis was the most frequently reported reaction. Periorbital edema was reported in two patients, and lacrimation was reported in a published study. Blepharospasm, keratitis, and decreased visual acuity were reported once each in patients treated with combination chemotherapeutic regimens containing doxorubicin. These reactions usually resolved rapidly on discontinuation of the drug. Conjunctivitis frequently followed accidental ocular exposure to doxorubicin. All but a few of these reactions cleared within 24 hours of exposure. The infrequent nature and usually rapid resolution of these ocular adverse reactions suggest that when ocular toxicities occur in patients undergoing doxorubicin-containing chemotherapy, the cautious reintroduction of doxorubicin, if further antineoplastic therapy is indicated, should be considered. PMID- 2596553 TI - Analysis of radiation failure after uveal melanoma brachytherapy. AB - We analyzed the number of cycling cells in the DNA synthesis phase and in mitosis in two uveal melanomas unsuccessfully treated with iodine 125 brachytherapy. In one patient, the tumor appeared to have been radioresistant, whereas the other patient had a clinically inapparent area of tumor that was not included in the tumoricidal radiation field. In the first patient, there was uniform tumor cell cycling, whereas the second patient had cycling cells predominantly in the area that did not receive optimal radiation. This gradient of cycling tumor cells in the second patient was observed with both standard histologic examination (mitoses per high-powered field) and bromodeoxyuridine staining (DNA synthesis). The bromodeoxyuridine technique was significantly more sensitive than standard histologic examination in the detection of cycling cells. PMID- 2596555 TI - Glaucoma lexicon. PMID- 2596554 TI - Trigeminal schwannoma as a cause of chronic, isolated sixth nerve palsy. AB - We treated two patients with trigeminal schwannomas, each of whom had an isolated, ipsilateral, abducens nerve palsy. Both patients initially had normal computed tomographic scan results and no neurologic signs of trigeminal nerve dysfunction. Trigeminal dysfunction did not develop until several years after the initial sixth nerve palsy, at which time a repeat examination disclosed the schwannoma. Accurate detection of a trigeminal schwannoma requires a careful clinical examination and appropriate neuroimaging studies. When such studies give normal results, they should be repeated if symptoms worsen or if new symptoms develop. PMID- 2596556 TI - Corneal epithelial defects after smoking crack cocaine. PMID- 2596557 TI - Multifocal choroiditis uveitis occurring after herpes zoster ophthalmicus. PMID- 2596559 TI - Asymmetric pigment dispersion syndrome in a patient with unilateral Horner's syndrome. PMID- 2596560 TI - Acute glaucoma following fluid-gas exchange in a phakic patient. PMID- 2596558 TI - Bilateral acute retinal necrosis syndrome. PMID- 2596561 TI - A modified scleral punch for filtration surgery. PMID- 2596562 TI - A combined iris retractor and irrigation cannula for congenital-cataract surgery. PMID- 2596563 TI - Saline for contact lens ophthalmoscopy and photocoagulation. PMID- 2596564 TI - Relaxed skin tension line incision for dacryocystorhinostomy. PMID- 2596565 TI - Multiple scleral ruptures after blunt ocular trauma. PMID- 2596566 TI - Effect of squinting on the pattern electroretinogram. PMID- 2596567 TI - Corneal topography of early keratoconus. PMID- 2596568 TI - Increase of the short-term fluctuation of the differential light threshold around a physiologic scotoma. PMID- 2596569 TI - Human lipoprotein binding to schistosomula of schistosoma mansoni. Displacement by polyanions, parasite antigen masking, and persistence in young larvae. AB - It was previously shown by the authors that the binding of human low-density lipoprotein (LDL) to the surface of schistosomula inhibits the binding of human anti-schistosomal antibodies and is inhibited by suramin. Here, three questions were considered. 1) Are LDLs bound to schistosomula displaced from the membrane by polyanions? 2) Does bound LDL mask or hide antigens recognized by human anti schistosomal antibodies? 3) Is LDL, binding capability present when the larvae enter the blood stream? The first question was tested by measuring the percentage of the schistosomular surface membrane covered by LDL after exposure to LDL with or without dextran sulfate or suramin. The bound LDL was visualized with polyclonal goat anti-human apolipoprotein B (anti-apo B) antibodies and peroxidase-conjugated secondary antibodies. After overnight culture in 20 micrograms/300 microliters LDL, 84.0% +/- 0.3% of the parasite surface was covered by LDL reaction product. When the polyanions suramin or dextran sulfate were added to the cultures for 30 minutes, only 59.7% +/- 4.9% of the surface was covered by reaction product, demonstrating that the LDL was partially displaced from the membrane by these compounds. The second question was tested by measuring the binding of human and mouse monoclonal anti-schistosomal antibodies before and after exposure to LDL, with or without partial removal of the bound LDL by suramin. LDL partially inhibited antibody binding in a reversible fashion. The LDL clearly masked parasite antigens, most probably by steric hindrance. However, there may be competitive inhibition of antibody binding by the LDL as well, because human anti-schistosomal antibodies inhibited LDL binding to worms and both human anti-schistosomal antibody and LDL binding to schistosomula were inhibited by suramin. Finally, the third question was tested by quantitative immunofluorescence. The LDL binding capability persisted and nearly doubled by 72 hours after transformation from cercariae. These experiments demonstrated that LDL bound to the surface of schistosomula through the time they enter the blood stream. LDL bound to the parasite surface may help the parasite to evade antibody dependent cytotoxic reactions by masking parasite antigens. PMID- 2596570 TI - Transin/stromelysin expression in rheumatoid synovium. A transformation associated metalloproteinase secreted by phenotypically invasive synoviocytes. AB - Transin is a neutral metalloproteinase whose mRNA was first isolated from rat fibroblasts that had undergone malignant transformation. The protein is highly expressed in malignant rather than benign animal tumors. Its human analog is stromelysin, a 51-kd metalloproteinase initially isolated from cultured human synoviocytes. Northern blot analysis demonstrated that rheumatoid arthritis synovial tissue contained significantly higher levels of stromelysin mRNA than did osteoarthritis synovial tissue. Cultured synoviocytes were also shown to express stromelysin mRNA, and an affinity-purified anti-peptide antiserum to stromelysin specifically immunoprecipitated the stromelysin protein from the conditioned medium of cultured explant rheumatoid synoviocytes. Immunohistochemical staining of rheumatoid synovium demonstrated specific cytoplasmic staining of cells of the synovial lining layer, stromal fibroblasts, and endothelial cells. Osteoarthritic synovia showed significantly less stromelysin staining. Similarly, rheumatoid synovia demonstrated marked nuclear staining for the proliferation- and transformation-associated Myc oncoprotein. In contrast, osteoarthritic synovia showed negligible staining. These results support the belief that the proliferative, invasive behavior of rheumatoid synoviocytes reflects the expression of biochemical features generally associated with phenotypically transformed, malignant tumors. Clearly not a malignancy, the rheumatoid synovium appears to be paracrine driven by mediators generated in local inflammatory milieu. PMID- 2596571 TI - Regional heterogeneity of elastin and collagen gene expression in intralobar arteries in response to hypoxic pulmonary hypertension as demonstrated by in situ hybridization. AB - In situ hybridization was used to determine the morphologic distribution of tropoelastin and alpha 1(I) procollagen mRNA expression in elastic intralobar arteries from neonatal calves with hypoxic pulmonary hypertension induced by a 15 day exposure to a simulated altitude of 1500 m. In vessels from normotensive control animals, low levels of hybridizable tropoelastin mRNA were detected in smooth muscle cells (SMC) of the inner media associated with large elastic lamellae. Compared to control arteries, vessels from hypertensive animals demonstrated a markedly different pattern of hybridization. In these arteries, strong hybridization signals for tropoelastin mRNA were seen in SMC lying between the elastic lamellae of the outer media, and the density of labeling associated with these medial cells decreased progressively toward the lumen. Endothelial and adventitial cells in both control and hypertensive arteries were negative for tropoelastin mRNA. Type I procollagen mRNA was dispersed through the media of control arteries, and in hypertensive calves, the hybridization signal was more intense and was unevenly distributed through the media similarly to that for tropoelastin mRNA. Adventitial cells were strongly positive for procollagen mRNA, and the signal was equally intense for both control and hypertensive arteries. Cells that had no detectable tropoelastin mRNA were noted in the outer media of both control and hypertensive vessels. These cells occurred as broad circumferential bands in the normotensive artery and as nodular foci in the hypertensive artery. Immunocytochemical studies with antibodies to smooth muscle specific actin, desmin, and vimentin demonstrated that cells within these foci, as well as tropoelastin mRNA-positive cells, were SMC. These studies demonstrate that expression of tropoelastin and procollagen mRNA was differentially stimulated by pulmonary hypertension within specific regions and SMC populations of the vascular wall. PMID- 2596572 TI - Endothelial-cell injury in cutaneous acute graft-versus-host disease. AB - The presence of an erythematous skin rash and hemorrhagic complications in acute graft-versus-host disease (GVHD) suggest that the vasculature may be involved in the immunopathologic process. We reviewed endothelial and vascular histopathologic changes on light microscopy and on immunoperoxidase stained sections of skin biopsies obtained from 41 HLA-identical allogeneic marrow transplant recipients with at least grade 2 GVHD. Biopsies taken from 14 allogeneic HLA-identical bone marrow transplant recipients who never developed GVHD were used as controls. Sections were evaluated for evidence of immunologic vascular injury using the rank file analysis of histologic features, expression of HLA-DR antigen, and the distribution of fibrin and factor VIII-related antigen (F VIII RAg). Patients with acute GVHD had significantly greater intimal lymphocytic infiltrates, perivascular nuclear dust deposition, perivascular F VIII Rag extravasation and deposition and vascular proliferation than controls. We find significantly greater endothelial injury in GVHD patients, which may represent primary immunologic injury to the vasculature. The clinical findings in acute GVHD probably result from cumulative endothelial as well as epithelial injury. PMID- 2596573 TI - Diethylnitrosamine-induced pulmonary endocrine cell hyperplasia and its association with adenomatosis and adenocarcinoma in rabbits. AB - Pulmonary endocrine cells are suspected of being the precursors for small cell carcinoma of the lung (SCCL). The purpose of this study was to determine whether Diethylnitrosamine (DEN) can induce SCCL in rabbits. New Zealand white rabbits were injected subcutaneously with 20 mg/kg body weight of DEN, twice per week, starting when they were 1 week old. Controls received saline vehicle only. The animals were sacrificed 6 to 8.5 months after the first injection and lung tissues were processed for light microscopy. Using serotonin (5-HT) as a marker for the endocrine cells, tissue sections were stained immunohistochemically by the avidin-biotin complex method. In both control and DEN-treated animals, serotonin-immunoreactive cells organized into neuroepithelial bodies (NEBs). There was an apparent increase in the size, number, and stainability of NEB in DEN-injected animals. A majority of these NEBs were localized in the alveolar duct region. Small foci of adenomatosis and well-differentiated adenocarcinomas, which sometimes coexisted with hyperplastic pulmonary endocrine cells, were also found in the DEN-treated rabbits. PMID- 2596574 TI - Pathologic findings in adenosine deaminase deficient-severe combined immunodeficiency. II. Thymus, spleen, lymph node, and gastrointestinal tract lymphoid tissue alterations. AB - Eight autopsies of patients with adenosine deaminase deficient-severe combined immunodeficiency disease (ADA-SCID) were reviewed with special emphasis on the lymphoid tissues. The thymus histology in five cases was remarkably uniform, whether or not prior ADA enzyme replacement or immunologic reconstitution therapy had been administered. Lymph nodes and spleens in all cases examined showed a residual nonlymphoid architectural framework corresponding to usual T and B cell zones found in normals. The development of an extranodal, monoclonal IgA lambda B cell immunoblastic lymphoma as a terminal event in one patient after several years of successful ADA enzyme replacement therapy through multiple red blood cell transfusions is described. In another patient with long-term ADA enzyme replacement, a terminal autoimmune hemolytic anemia developed. Autopsy revealed severe deposits of iron in the B cell zones of the lymph nodes, which is an unusual location. In addition, iron deposits outlined the splenic trabeculae, as well as the ring fibers and bridging fibers of the splenic sinuses. PMID- 2596575 TI - Increased vesicular transport and decreased mitochondrial content in blood-brain barrier endothelial cells during experimental autoimmune encephalomyelitis. AB - Mechanisms involved in the loss of blood-brain barrier function in Lewis rats with experimental autoimmune encephalomyelitis (EAE) were examined using horseradish peroxidase (HRP) as a tracer. In animals injected with HRP before fixation, tracer was observed in two intracytoplasmic compartments: multivesicular bodies (presumably secondary lysosomes) and transcytotic vesicles. Quantitative morphometry of electron micrographs of capillary endothelial cells demonstrated a 5.2-fold increase in these vesicles. This increase in vesicular transport was associated with a decrease in mitochondrial content from 13.7% of the endothelial cytoplasmic area in the normal rat to 4.2% in EAE rats at the height of clinical disease. These alterations correlated with the clinical course of EAE. In animals infused with tracer after fixation, tracer was restricted to areas of cellular inflammation. Immunogold staining of endogenous albumin demonstrated the presence of albumin in cytoplasmic vesicles and in channel-like tubular structures adjacent to endothelial cell junctions. These results indicate that there is a role for vesicles in transendothelial cell transport and edema formation in animals with EAE. PMID- 2596576 TI - Fodrin as a differentiation marker. Redistributions in colonic neoplasia. AB - Fodrin (nonerythroid spectrin) is a 475,000 molecular weight (MW) (apparent) heterodimeric actin-binding protein usually found in mature cells at the cytoplasmic face of the plasma membrane. While its precise role is uncertain, it may participate in the establishment and/or maintenance of cell polarity, shape, and specialized receptor domains. In polarized epithelial cells, an asymmetric distribution of fodrin appears to signal phenotypic maturity. Using immunohistochemical techniques, the distribution of fodrin in enterocytes during normal crypt-to-villus maturation, and in adenomas, adenocarcinomas, and cultured Madin-Darby Canine Kidney (MDCK) cells has been studied and its abundance quantitated by immunoblotting and digital immunofluorescent confocal microscopy. During normal maturation, fodrin was found to assemble at the apex of the enterocyte, presumably in the terminal web, only in those cells near the villus tip. Villin was found in an apical location in both crypt and surface enterocytes. In adenocarcinomas of the colon (n = 11), there were enhanced levels of fodrin at the apex, and an approximately threefold increase in the total amount of fodrin per cell relative to normal crypt enterocytes. An increased percentage of this protein was also found in the cytoplasm. Adenomas (n = 7), nonconfluent MDCK cells in culture, and two (of two) cases of ductal carcinoma of the breast also demonstrated enhanced cytoplasmic and total fodrin. Supranormal levels of fodrin at the apex of enterocytes were also observed in Crohn's disease samples and in the normal-appearing enterocytes adjacent to a tumor. It is hypothesized that increased apical fodrin may signal a reaction of the microvillar brush border to pathologic stress, while increased cytoplasmic and total pools of fodrin may mark neoplastic activity. These findings may be of diagnostic value, particularly in the evaluation of small biopsies or cytologic material. PMID- 2596577 TI - Animal model of human disease. Citrullinemia (argininosuccinate synthetase deficiency). PMID- 2596578 TI - Atherosclerosis- and age-related multinucleated variant endothelial cells in primary culture from human aorta. AB - Endothelial cells were cultured from human aortas and inferior venae cavae of autopsied subjects ranging in age from infancy to 85 years. Endothelial cells in 32 of more than 100 attempted cultures were pure enough for evaluation. Emerged endothelial cells in primary culture were classified into two types: typical endothelium and variant endothelium. Typical endothelial cells were small, round to polygonal shaped, and were arranged uniformly. Their diameter ranged from 50 to 70 microns. Variant endothelial cells were larger, ranging from 100 to 200 microns in diameter, and giant endothelial cells measuring more than 250 microns in diameter were scattered among them. Variant endothelial cells were usually multinucleated and possessed endothelium-specific markers of vWF and Weibel Palade bodies. No incorporation of [3H]thymidine was found in the nuclei of cultured variant endothelial cells. Although most cultured endothelial cells were of the typical type, variant endothelial cells were interspersed throughout the culture. The ratio of variant endothelial cells to typical cells correlated well with the severity of atherosclerosis, but less so with aging. The number of variant endothelial cells in cultures from inferior venae cavae was slight and constant throughout all age groups. The presence of multinucleated endothelial cells in in vivo aortas was confirmed by both scanning and transmission electron microscopy. They sometimes existed in colonies in the aortas from elderly subjects with intimal-thickened or advanced atherosclerotic lesions. These results indicate that variant endothelial cells were present in vivo and their ratio in primary culture reflected the in vivo population. It is likely that these cells were formed by adhesion of adjacent typical endothelial cells and that this process was affected more by atherosclerosis than by aging. Although it is not clear if the multinucleated variant cells were formed before the formation of atherosclerotic plaque or after the plaque formation, they will contribute to further development of atherosclerotic lesions, which in turn cause malfunction of the cell membrane. We suggest that there is a cyclic effect of these processes for multiplication of the variant endothelial cells and advancement of atherosclerotic lesions. PMID- 2596579 TI - High frequency of spontaneous acute myocardial infarction due to small coronary artery disease in dead (NZWxBXSB)F1 male mice. AB - To determine whether or not male (NZWXBXSB)F1 [WXB)F1) mice exhibiting a lupus like syndrome died of acute myocardial infarction (MI), and whether acute MI is directly related to small coronary artery disease, acute and old MIs were examined histologically in 55 dead (WXB)F1 male mice and 30 age-matched, surviving (WXB)F1 male mice used as a control group. In each heart from the 15 dead mice with MI and the five surviving mice without MI, 300 to 400 5-microns thick serial sections were made; every fourth section was stained. Acute MI was found in 35 (64%) dead mice and in one (3%) survivors, whereas old MI was found in 50 (91%) dead mice and 17 (57%) survivors: a significant difference between the dead and surviving mice. The MIs were numerous, scattered, and small in most mice. Quantitative analysis revealed that the percentage of acute MI and old MI in the left ventricular (LV) wall was 6% +/- 11% and 3% +/- 3% in the dead group, and 0.4% and 2% +/- 3% in the control group. This indicated that recurrent acute MI is a major factor in the death of the mice. Although all the epicardial major coronary arteries of the (WXB)F1 male mice were intact, significant stenoses were noted in the intramyocardial small arteries. The serial sections in the 15 dead mice with MI revealed 1) segmental occlusive thrombi in the infarct-related small coronary artery in 14 of the 20 foci of acute anemic MIs, two of the 18 foci of acute hemorrhagic MIs, and four of the 58 foci of old MIs; and 2) segmental intimal thickenings in the infarct-related small artery in six of the 20 foci of acute anemic MIs, two of the 18 foci of acute hemorrhagic MIs, and 56 of the 58 foci of old MIs. There was no evidence of small coronary artery disease in the surviving mice without MI. The thrombus would result in thickened intima as MI progresses from the acute to the old stage. Because it was established that acute MI of hemorrhagic type follows reperfusion after transient occlusion of the coronary artery, hemorrhagic acute MI with rare incidence of thrombi in this mouse suggests that thrombolysis occurs after occlusion due to thrombus formation. Thus, the pathogenesis of multiple MIs is occlusive thrombi, recanalization in small coronary arteries or both. Some of the mice had dilated cardiomyopathy (DCM)-like features (marked LV dilatation).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2596580 TI - Myosin light chain phosphorylation and tension potentiation in mouse skeletal muscle. AB - In intact mammalian fast-twitch skeletal muscle, a quantitative relationship exists between the phosphate content of myosin P-light chain (PLC) and the extent of isometric twitch tension potentiation. It has been proposed that PLC phosphorylation causes twitch potentiation in intact muscle by rendering the contractile element more sensitive to activation by Ca2+. If this hypothesis is correct, then an obligatory experimental outcome is that the slope of the "PLC phosphate vs. isometric tension potentiation (ITP)" relationship should increase when the amount of Ca2+ available to activate the contractile element is decreased. Intact mouse extensor digitorum longus muscles were studied in the absence and presence of sodium dantrolene, an agent that partially inhibits Ca2+ release from the sarcoplasmic reticulum (SR). Treatment of muscles with dantrolene produced a 73% reduction in isometric twitch tension and an approximately threefold increase in the slope of the PLC phosphate vs. ITP relationship. Under experimental conditions that produced fused, tetanic contractions equal to 0.52, 0.72, 0.94, and 1.0 force production, contraction induced changes in PLC phosphate content were directly proportional to the extent of contractile element activation, whereas the extent of ITP was inversely proportional to the extent of contractile element activation. These data indicate that the slope of the PLC phosphate vs. ITP relationship varies inversely as a function of the amount of Ca2+ that is released from the SR to activate the contractile element during both twitch and fused, submaximal tetanic contractions. Furthermore, these findings support the hypothesis that ITP in intact skeletal muscle is due to a PLC phosphorylation-induced sensitization of the contractile element to activation by Ca2+. PMID- 2596581 TI - Intracellular [Ca2+] and inositol phosphates in avian nasal gland cells. AB - Isolated cells from the nasal salt gland of ducklings (Anas platyrhynchos) were evaluated as a model system for the study of the muscarinic activation of exocrine ion secretion. Cells loaded with the fluorescent probe indo-1 were used to study changes in intracellular Ca2+ concentration [( Ca2+]i) after stimulation. Changes in inositol phosphate generation and oxygen consumption were also determined. Loading with the acetomethoxy ester form of indo-1 (indo-1/AM) was rapid, and intracellular cleavage of the ester was essentially complete. Leakage of the dye was negligible over the time course of measurements (up to 20 min). Resting [Ca2+]i was approximately 100 nM. Stimulation with carbachol resulted in progressive increases in the generation of inositol phosphates and rapid four- to fivefold increases in [Ca2+]i. At normal extracellular Ca2+ concentrations, [Ca2+]i remained elevated (approximately 3 times resting levels) for as long as stimulation continued. Experiments showed that the increases in [Ca2+]i were comprised of a combination of release of Ca2+ from intracellular stores and an enhanced entry of Ca2+ from the extracellular medium. It is specifically this latter process that produces the sustained elevations in [Ca2+]i that are the essential signal for secretory activity. PMID- 2596582 TI - Lowering Po2 induces epithelium-dependent relaxation in isolated canine bronchi. AB - This study was designed to investigate whether the respiratory epithelium can modulate the tone of the underlying smooth muscle in response to decreases in partial pressure of O2 (PO2). Canine bronchial segments with or without epithelium (diameter, 4-6 mm; length, 50-60 mm) were mounted in organ chambers and perfused intraluminally with modified Krebs-Ringer bicarbonate solution [temperature, 37 degrees C; PO2 varying from 600 (control) to 40 mmHg; PCO2, 36 mmHg]. Isometric tension was recorded by means of stirrups passed through the wall of the central part of the bronchial segment. During contractions to carbachol, the tissues with epithelium showed epithelium-dependent relaxations when the PO2 was decreased. The level of relaxation was dependent on the PO2. The epithelium-dependent relaxation could not be blocked by the following agents: indomethacin, methylene blue, propranolol, or tetrodotoxin (antagonists or blockers of cyclooxygenase, guanylate cyclase, beta-adrenoceptors, and sodium channels, respectively). The epithelium-dependent relaxation was not accompanied by the release of an assayable relaxing factor in the bronchial lumen. The experiments suggest that 1) lowering the PO2 induces the epithelium to release a relaxing factor(s), which is neither a product of cyclooxygenase nor endothelium derived relaxing factor; 2) a local reflex mechanism is not involved in the phenomenon; and 3) the relaxing factor(s) either is not released into the bronchial lumen or, if it is, is catalyzed rapidly in the lumen on release. PMID- 2596583 TI - Inhibition of angiotensinogen production by angiotensin II analogues in human hepatoma cell line. AB - The aim of this study was to examine in Hep G2, a human hepatoma-derived cell line, the presence of angiotensin II (ANG II) receptors and the effect of ANG II and its analogues on angiotensinogen production. The presence of ANG II receptors was demonstrated using a long-acting ANG II analogue, 125I-labeled [Sar1]ANG II. A single class of specific binding sites was identified in these cells with a dissociation constant (Kd) of 2 nM. The number and affinity of these binding sites were not changed by [Sar1]ANG II treatment over 24 h. ANG II showed an inhibitory effect on angiotensinogen production. [Sar1]ANG II also exhibited a similar inhibitory effect as that of ANG II but to a greater extent and therefore was used throughout these studies. [Sar1]ANG II inhibited angiotensinogen production in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) of 2 nM. Other ANG II analogues showed similar effects on angiotensinogen production. In order of decreasing ability, they were [Sar1]ANG II greater than [Sar1-Ala8]ANG II greater than [Sar1-Val8]ANG II greater than [Sar1-Val5-(Br5)-Phe8]ANG II greater than [Sar1-Val5-DPhe8]ANG II. Results of these studies show that the Hep G2 cell possesses specific ANG II receptors and that [Sar1]ANG II induces a dose-dependent inhibition of angiotensinogen production in this system. PMID- 2596584 TI - Glucocorticoids inhibit acetylcholine-induced current in chromaffin cells. AB - The effects of dexamethasone, a synthetic glucocorticoid, on membrane excitability and on the acetylcholine (ACh)-induced inward current (IACh) were studied in dispersed guinea pig adrenal medullary cells by using the whole cell version of the patch-clamp technique. Bath application of 10 microM dexamethasone had no effect on the resting membrane conductance or voltage-gated Na+, Ca2+, or K+ channels, whereas it reversibly inhibited the IACh at a holding potential of 70 mV. Intracellular application of dexamethasone through the patch electrode did not modify the IACh. Application of 10 microM dexamethasone neither shifted the dose-response curve of the peak IACh to the right [dissociation constant (Kd) = 50 microM] nor affected its Hill coefficient (1.2) but inhibited the current amplitudes by approximately 41% in the cells sufficiently pretreated with dexamethasone. Furthermore, fractional inhibition of the IACh at the end of approximately 50-s application was the same for any concentration of ACh (3-100 microM). The dose-response curve of the inhibition by dexamethasone showed a good fit to the theoretical line assuming an inhibition constant (Ki) of 10 microM and a Hill coefficient of 1. Hydrocortisone 21-hemisuccinate sodium salt (25 microM) and prednisolone 21-hemisuccinate sodium salt (25 microM) inhibited the IACh to a lesser extent than 25 microM dexamethasone. These results suggest that dexamethasone binds to the specific site on the outer cell membrane, probably on the ACh receptor-coupled channel, and inhibits the IACh in a noncompetitive manner, thus controlling the immediate catecholamine release from the adrenal medulla. PMID- 2596585 TI - Protein metabolism during nutrient deprivation and refeeding of neonatal heart cells. AB - Pathological conditions or nutrient deprivation in the heart cause an imbalance between rates of protein synthesis and degradation, often resulting in a severe depletion of cardiac protein. We used cultured neonatal rat heart cells, a model system exhibiting positive nitrogen balance, to examine the effects of 10 h of starvation on myocardial glucose and protein metabolism. Cellular capacity for glucose utilization was depressed after starvation, as evidenced by lower hexokinase and other glycolytic enzyme activities and a 21% decrease in glucose usage. A 21.0% decrease in protein synthetic rate and an increase in protein degradation rate combined to yield a 29.5% decrease in total cellular protein during starvation. Degradation rates increased 29.0, 46.7, and 59.6% in 2-, 24-, and 96-h prelabeled cells, respectively, indicating that lability increased with half-life of proteins. During refeeding of starved, cultured cells, at least three proteins were synthesized at a lower rate. At the same time, proteins with approximate molecular masses of 45, 84, 92, and 174 kDa exhibited increased synthesis. PMID- 2596586 TI - Effects of cholera toxin on gene expression in brown preadipocytes differentiating in culture. AB - To investigate the cellular control of the recruitment process in brown adipose tissue, the ability of cholera toxin to influence the differentiation of brown preadipocytes developing in culture was investigated. Stromalvascular cells obtained from the brown adipose tissue of 3-wk-old rats were grown in culture for 6-7 days in the presence or absence of cholera toxin. It was found that cholera toxin treatment decreased the expression of the actin gene (indicating an increased degree of differentiation), while at the same time promoting the expression of the genes coding for the mitochondriogenesis marker cytochrome-c oxidase and for the adipocyte conversion marker lipoprotein lipase (all followed at the mRNA level). Chronic cholera toxin treatment also increased the total amount of protein per cell in culture, and a specific cholera toxin-induced 35 kDa protein was identified. It was concluded that (in contrast to the case suggested for white preadipocytes) cholera toxin treatment of brown preadipocytes may not only affect the activity of catabolic enzymes but may also directly promote the differentiation process, indicating that this process is under beta adrenergic control in the adapting animal. PMID- 2596587 TI - Cardiolipin-sensitive phospholipase C in subcellular fractions of rabbit myocardium. AB - Phosphatidylinositol-specific phospholipase C was characterized in the soluble phase and in membrane fractions prepared from rabbit myocardium. Four subforms of soluble phospholipase C were identified and characterized. Activity of one subform was inhibited 80% when cardiolipin was present in substrate vesicles, whereas three subforms were stimulated 2- to 10-fold by cardiolipin. A cationic subform, molecular mass 67 kDa, was stimulated threefold when cardiolipin comprised 2% of the total phospholipid and fivefold when it comprised 12%. The major mechanism for the cardiolipin effect was a decrease in the apparent Michaelis constant (Km) of this subform for substrate. Competition experiments were consistent with binding of this subform to cardiolipin. Phospholipase C activity was present in mitochondrial, microsomal, and sarcolemmal membrane fractions that were essentially free of contamination by cytosol. Detection of membrane-associated phospholipase C was facilitated by cardiolipin. Thus rabbit myocardium contains multiple subforms of soluble phospholipase C that differ substantially in surface charge, molecular mass, and sensitivity to cardiolipin. Anionic phospholipids may be important determinants of intracellular distribution of phospholipase C in myocardial tissue. PMID- 2596588 TI - Modification of leucine transport across bovine pigment epithelium by metabolic stress. AB - The transport of leucine in the apical-to-basal (retina to choroid) direction across the isolated bovine retinal pigment epithelium is mediated predominantly by the L amino transport system at low carrier (10 microns) concentrations. There is no evidence of an active or facilitated transport system operating in the opposite direction. The identification of the L system is based on the lack of sodium dependence, specific inhibition of leucine transport by 2-aminobicyclo (2,2,1)-heptane-2-carboxylic acid (BCH), and the demonstration of trans stimulation. Lysine, glutamate, and 2-methylaminoisobutyric acid (MeAIB) did not provide any competitive inhibition. Ouabain and iodoacetate were also ineffective in modifying leucine transport. The transport mediated by the L system was markedly temperature sensitive, whereas no temperature dependence was apparent in the transport of leucine in the basal-to-apical direction (choroid to retina). When treated with dinitrophenol (DNP), the transport of leucine in the apical-to basal direction was greatly enhanced, but no effect was observed on the leucine movement in the opposite direction. Azide and rotenone had an effect similar to DNP, as did reducing the partial pressure of O2 to less than 40 Torr. The enhancement of transport appeared to be mediated by the activation of an ancillary system, since it was susceptible to different classes of metabolic and competitive inhibitors as well as the observed ionic dependency. After DNP treatment, the transport of leucine was inhibited by lysine and BCH, revealed a sodium dependence, and could be inhibited by iodoacetate. The characteristics of the enhanced transport appear to be similar to those of the recently described G system(s) of amino acid transport. PMID- 2596590 TI - Osmoregulatory fluxes of myo-inositol and betaine in renal cells. AB - Renal medullary cells contain high concentrations of "compatible" organic osmolytes, such as myo-inositol, betaine, sorbitol, and glycero phosphorylcholine. These organic osmolytes accumulate as an osmoregulatory response to the high and variable interstitial NaCl concentration that is part of the urinary concentrating mechanism. Madin-Darby canine kidney (MDCK) cells in culture were previously shown to accumulate myo-inositol and betaine in response to increased NaCl. These organic osmolytes are taken up by sodium-dependent active transport into the cells from the medium. The maximum concentration is not reached until 2-4 days after an increase in medium osmolality. The purpose of this study was to characterize the response to a decrease in medium osmolality of cells that had been grown at a high osmolality. The initial response to decreased osmolality was a rapid, transient efflux of both myo-inositol and betaine from the cells. Efflux was greatest during the first 15 min and resulted in a reduction of cell myo-inositol and betaine by almost 13 and 22%, respectively, after 3 h. Active myo-inositol and betaine influx fell more slowly, reaching a lower limit after approximately 1-2 days. The reduced influx was followed by progressive decrease in cell myo-inositol and betaine to approximately 30% of the initial value after 6 days. Thus, after a decrease in medium osmolality, MDCK cell myo-inositol and betaine fell because of a rapid, transient increase in efflux and a slow, sustained decrease in active influx. PMID- 2596589 TI - Hyperthyroid adult rat cardiomyocytes. II. Single cell electrophysiology and free calcium transients. AB - The effects of hyperthyroidism on electrophysiological properties and intracellular free calcium transients in single adult rat cardiomyocytes were studied using conventional microelectrodes and time-resolved single cell fura-2 fluorescence microscopy. Under control conditions, resting membrane potentials and triggered action potentials were not different in euthyroid and hyperthyroid myocytes. Calcium transients produced by electrical stimulation, however, were markedly abbreviated in hyperthyroid myocytes. During a train of stimuli, the duration of the calcium transients at half peak amplitude (half time) was 124 +/- 14 ms at the fifth beat in hyperthyroid cells vs. 287 +/- 35 ms in euthyroid cells. Isoproterenol (1 microM) prolonged time to 50% repolarization (APD50) of the action potentials and increased the peak calcium transients in both euthyroid and hyperthyroid myocytes. It also shortened the half time of the calcium transients in euthyroid myocytes but had little effect on the half time in hyperthyroid cells. These data are consistent with the electrophysiology and mechanical performance in intact euthyroid and hyperthyroid cardiac tissues, and the intrinsic changes in hyperthyroid tissues can therefore be illustrated in single ventricular myocytes. Furthermore, the results suggest that alterations in intracellular calcium handling by sarcoplasmic reticulum may account for contractile changes of the heart induced by hyperthyroidism. PMID- 2596591 TI - Low-affinity transport of pyroglutamyl-histidine in renal brush-border membrane vesicles. AB - These studies were performed to determine if a low-affinity carrier is present in the luminal membrane of proximal tubular cells for the transport of the dipeptide, pyroglutamyl-histidine (pGlu-His). We have previously described the existence of a specific, high-affinity, low-capacity [transport constant (Kt) = 9.3 X 10(-8) M, Vmax = 6.1 X 10(-12) mol.mg-1.min-1] carrier for pGlu-His in renal brush-border membrane vesicles. In the present study, we sought to demonstrate that multiple carriers exist for the transport of a single dipeptide by determining whether a low-affinity carrier also exists for the uptake of pGlu His. Transport of pGlu-His into brush-border membrane vesicles was saturable over the concentration range of 10(-5)-10(-3) M, yielding a Kt of 6.3 X 10(-5) M and a Vmax of 2.2 X 10(-10) mol.mg-1.min-1. Uptake was inhibited by the dipeptides glycyl-proline, glycyl-sarcosine, and carnosine but not by the tripeptide pyroglutamyl-histidyl-prolinamide. We conclude that 1) pGlu-His is transported across the luminal membrane of the proximal tubule by multiple carriers and 2) the lower affinity carrier, unlike the higher affinity carrier, is nonspecific with respect to other dipeptides. PMID- 2596592 TI - Voltage-activated cation transport in human erythrocytes. AB - We report here the effects of membrane potential on the permeability of the human erythrocyte to Na, K, and Ca. Membrane potential was changed either by varying the K concentration gradient in the presence of valinomycin or by varying the concentration gradient of the permeant anion nitrate in the presence of 4,4' diisothiocyanostilbene-2,2'-disulfonic acid. When the membrane potential was changed from inside negative (-10 mV) to inside positive (greater than 40 mV), influx, efflux, and net flux of Na and K increased. Marked net cation loss and cell shrinkage occurred in the absence of a chemical gradient for Na and K. This voltage-dependent increase in Na and K conductance is partially inhibited by 10 microM ruthenium red and persists when the membrane potential is returned to -10 mV after transient exposure to inside-positive potentials. A similar voltage dependent behavior was found for Ca influx. The voltage-activated Ca influx is almost completely inhibited by 10 microM ruthenium red. PMID- 2596594 TI - Whole body protein synthesis: studies with different amino acids in the rat. AB - These studies were undertaken to determine to what extent constant infusion measurements and plasma sampling could provide sensible answers for rates of whole body protein turnover and also which amino acid would be the most representative probe of whole body protein turnover. Whole body protein synthesis rates were estimated in 70-g rats with L-[U-14C]threonine, L-[U-14C]lysine, L-[U 14C]tyrosine, L-[U-14C]phenylalanine, and L-[1-14C]leucine by either simultaneous tracer infusion of four amino acids or by injections of large quantities of 14C labeled amino acids. In the infusion experiment, indirect estimates of whole body protein turnover based on free amino acid specific radioactivity and stochastic modeling were compared with direct measurement of the incorporation of the tracer into proteins. These two methods of analysis provided similar results for each amino acid, although in each case fractional synthesis rates were lower (by between 26 and 63%) when calculations were based on plasma rather than tissue specific radioactivity. With the flooding-dose method, whole body fractional protein synthesis rates were 41.4, 25.6, 31.1, and 31.4% with threonine, lysine, phenylalanine, and leucine, respectively. These values were similar to those obtained by the continuous infusion method using tissue specific radioactivity for threonine and lysine. For leucine, however, the flooding-dose method provided an intermediate value between the two estimates derived either from the plasma or the tissue specific radioactivity in the infusion method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596593 TI - Oral verapamil and calcium and vitamin D metabolism in rats: effect of dietary calcium. AB - Prior studies showed that chronic oral verapamil administration increased plasma immunoreactive parathyroid hormone (irPTH) but decreased 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels in rats fed a high (1.2%)-Ca diet. These and other findings suggested that verapamil may induce target-organ PTH resistance. This study determined the effects of verapamil (4, 20, or 100 mumol.kg-1.day-1 for 2 wk) in rats fed high (1.2%)-, low-normal (0.47%)-, and low (0.02%)-Ca diets (higher irPTH levels). With 1.2 and 0.47% Ca diets, verapamil administration was associated with increases in irPTH (92 and 44%, respectively) and decreases in 1,25(OH)2D3 levels (22 and 21%, respectively), increases in duodenal Ca transport (13 and 8%, respectively), and increases in tibia mineral content (1.3 and 2.8%, respectively). The decrease in 1,25(OH)2D3 levels was caused by decreased production, not by increased clearance. In contrast, verapamil was without effect in rats fed the 0.02% Ca diet. Thus severe dietary Ca deficiency abolished the stimulatory effects of verapamil on irPTH levels, Ca absorption, and tibia mineral content. Importantly, these results indicate that verapamil, in contrast to nifedipine, appears not to have adverse effects on Ca homeostasis in rats, irrespective of dietary Ca intake. PMID- 2596595 TI - Energy expenditure during normo- and overfeeding in peripubertal children of lean and obese Pima Indians. AB - We investigated the hypothesis that peripubertal children born to obese parents have a lower 24-h energy expenditure during "weight maintenance" and/or in response to overfeeding when compared with children born to normal-weight parents. Sixteen Southwestern American Indians (12.4 +/- 1.4 yr, 55.5 +/- 14.1 kg, 30 +/- 8% body fat), eight offspring from obese parents [body mass index (BMI) = 40 +/- 6 kg/m2], and eight offspring from thin parents (BMI = 24 +/- 3 kg/m2) were admitted for 8 days to our metabolic ward. The 24-h energy expenditure was measured under eucaloric conditions and on the 3rd day of progressive overfeeding of a mixed diet, i.e., 150, 200, and 200% of weight maintenance on day 1, 2, and 3 of overfeeding. At base line, offspring of obese parents were heavier (64 +/- 15 vs. 47 +/- 6 kg, P less than 0.05) and tended to be fatter (34 +/- 8 vs. 26 +/- 9% body fat, P = 0.07), with a higher absolute fat mass (22 +/- 9 vs. 13 +/- 4 kg body fat, P less than 0.05) when compared with offspring of thin parents. During both normo- and over-feeding, the larger part of the variance in 24-h energy expenditure in the conditions of a respiratory chamber was accounted for by differences in fat-free body mass (54 and 68%, respectively), whereas differences in the level of spontaneous physical activity accounted for another 19 and 21%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596596 TI - Muscle sympathetic activity and norepinephrine release during mental challenge in humans. AB - Muscle sympathetic nerve activity (MSA; peroneal nerve) and arterial and femoral venous plasma norepinephrine (NE) were studied in 10 volunteers at rest, during a relaxation procedure (RELAX), and during two mental challenges, a word identification test (WIT) and a color word test (CWT). [3H]NE infusions were used to assess NE spillover to and clearance from plasma. Net NE overflow from the leg was calculated. RELAX reduced MSA and femoral venous NE concentrations. CWT increased blood pressure, cardiac output (thermodilution), and calf flow and reduced systemic vascular resistance. Responses to WIT were less marked. CWT increased MSA by 25%, femoral venous NE concentrations by 25%, and NE overflow from the leg by 26% at 3 min. Fractional epinephrine and [3H]NE extractions were flow related and decreased during CWT. The arterial contribution to femoral venous NE (about half) increased by 10% during CWT. Arterial NE levels and spillover increased, but NE clearance was unchanged. Femoral venous NE concentrations and NE spillover (not based on flow measurements) and regional NE overflow correlated with MSA. Thus NE concentrations in plasma reflect spillover rather than clearance at rest and during mental challenge. Biochemical and neurophysiological indexes of sympathetic activity correlate when assessed in the same region. Mental stress increases sympathetic activity in leg muscle. PMID- 2596597 TI - Regulation of ketone body flux in septic patients. AB - To assess the effect of sepsis on ketone body (KB) kinetics in humans, we measured in normal and septic subjects KB appearance rate (Ra) before (initial state) and during a rise of free fatty acids (FFA) level (intravenous infusion of a triglycerides emulsion). We studied normal subjects in postabsorptive state and septic patients when receiving an hypocaloric intravenous infusion of glucose and amino acids or 12 h after its interruption. When receiving glucose and amino acids infusion, septic patients had higher glucose and insulin levels than normal subjects, and despite lower FFA concentrations (255 +/- 44 vs. 480 +/- 51 mumol/l, P less than 0.05) comparable initial KB Ra (2.50 +/- 0.10 vs. 2.48 +/- 0.30 mumol.kg-1.min-1). Triglyceride infusion increased FFA to comparable values (septic 780 +/- 130, normal 730 +/- 45 mumol/l), but KB Ra rose in septic patients only to 3.7 +/- 1.1 instead of 7.7 +/- 1.1 mumol.kg-1.min-1 as in normal subjects (P less than 0.05). Somatostatin infusion decreased the hyperinsulinemia of septic patients but did not restore a normal ketogenesis. After interruption of nutriment infusion, septic patients had normal FFA levels and only mild hyperglycemia and hyperinsulinemia. Their initial KB Ra was not modified. However, their response of KB Ra (increase to 6.27 +/- 2.0 mumol.kg-1.min-1) to raised FFA levels (842 +/- 170 mumol/l) was comparable to the response of normal subjects. In conclusion, although septic patients receiving an hypocaloric parenteral nutrition had a depressed ketogenesis they were able to restore a normal ketogenic capacity after a short-time caloric deprivation. Glucose and/or insulin appears to have a major role in this modulation of hepatic ketogenesis. PMID- 2596598 TI - The glucose-galactose paradox in neonatal murine hepatic glycogen synthesis. AB - In adults glucose incorporation to glycogen is indirect after recycling from lactate. In neonates galactose entry to glycogen exceeds that for glucose, but the pathway is unknown. The pathway of hexose incorporation to glycogen was studied in 5-7-day-old rats and 6-h-old rats injected intraperitoneally (IP) with either double-labeled [6-3H]glucose (nonrecycling), [U-14C]glucose (recycling), or [6-3H]glucose and [U-14C]galactose in saline. In another group of pups, 1 g/kg of glucose or galactose was administered in addition to tracers to determine glycemia and net glycogen synthesis between 15 and 180 min after injection. Blood glucose increased from 3.4 +/- 0.4 to 8.5 +/- 1.5 mM in 5-7-day-old pups in response to IP glucose; there was no glycemic response to galactose, although galactose levels increased from 0.5 to 6.3 mM at 15 min. Hepatic glycogen increased after IP glucose from 14 +/- 2 at 15 min to 30 +/- 3 at 120 min (P less than 0.01), whereas after IP galactose glycogen was 44 +/- 6 mumol/g at 120 min (P less than 0.05). After IP glucose, 3H and 14C disintegration per minute in glycogen increased slowly with 14C exceeding 3H at 120 and 180 min. In contrast IP [14C]galactose resulted in a much greater peak of 14C incorporation into glycogen. The ratio of 3H to 14C in glycogen relative to the injectate after IP glucose decreased from 0.69 +/- 0.12 to 0.36 +/- 0.03 (P less than 0.01) between 15 to 180 min, whereas the ratio after galactose was 0.20 +/- 0.007 to 0.15 +/- 0.02 at these times. The 6-h-old pups also demonstrated augmented incorporation of [14C]galactose in glycogen relative to [3H-14C]glucose. In contrast to 5-7-day old pups there was no evidence of glucose recycling in 6-h-old pups. In conclusion galactose entry into glycogen exceeds that for glucose and is not dependent on recycling. Direct incorporation of galactose exceeds that for direct incorporation from [3H]glucose, suggesting a preferential utilization of galactose for neonatal glycogen synthesis. PMID- 2596599 TI - Glucocorticosteroids increase leucine oxidation and impair leucine balance in humans. AB - High-dose glucocorticoid treatment results in protein wasting. To determine whether such therapy affects leucine oxidation in the postabsorptive state and the disposal of dietary amino acids, eight normal subjects were studied twice in random order, once after 5 days of prednisone (20 mg three times daily) and on a second occasion without prednisone as a control. In the postabsorptive state prednisone therapy increased (P less than 0.05) plasma concentrations of leucine, alpha-ketoisocaproate, glucose, insulin, and C-peptide, as well as leucine carbon flux and oxidation calculated by means of isotope dilution techniques and [1 13C]leucine. During infusion of a chemically defined meal, total leucine carbon flux and oxidation increased similarly on both study days, but leucine oxidation was greater (P less than 0.01) during prednisone treatment; net leucine balance became positive on the control day but remained negative or zero on the prednisone study day despite higher (P less than 0.05) plasma insulin concentrations. These studies demonstrate that high-dose glucocorticoid treatment impairs the balance of the essential amino acid leucine in both the postabsorptive and absorptive states in humans. PMID- 2596600 TI - Mobilization of glucoregulatory hormones and glucose by hypothalamic locomotor centers. AB - Recent studies suggest that, in addition to classical humoral metabolic feedback mechanisms, the mobilization of glucoregulatory hormones and glucose in exercise may be regulated by motor centers in the brain. We, therefore, studied the effect of electrically stimulating the posterior hypothalamic locomotor region (PHLR) for 10 min in decorticated (n = 6) and alpha-chloralose-anesthetized (n = 8) cats. Blood pressure and heart rate were measured, and blood samples were drawn for analysis of hormones and metabolites before, during, and after 10 min of PHLR stimulation. Feedback from contracting muscles was prevented by neuromuscular blockade in decorticated cats and by the anesthesia in anesthetized cats. In decorticated cats, PHLR stimulation elicited increases (2 P less than 0.05) in glucose production (delta 54 +/- 16 mumol.min-1.kg-1), plasma glucose (delta 2.2 +/- 0.7 mmol/l), epinephrine (delta 4.9 +/- 1.8 pmol/l), norepinephrine (delta 2.2 +/- 0.9 pmol/l), glucagon (delta 16 +/- 5 pmol/l), decreases (2 P less than 0.05) in plasma insulin (delta 27 +/- 7 pmol/l), and increases (2 P less than 0.05) in blood pressure (delta 48 +/- 9 mmHg) and heart rate (delta 26 +/- 7 beats/min). In anesthetized cats, PHLR stimulation elicited increases (2 P less than 0.05) in glucose production (delta 12 +/- 4 mumol.min-1.kg-1), plasma glucose (delta 0.4 +/- 0.1 mmol/l), blood pressure (delta 39 +/- 7 mmHg), and heart rate (delta 28 +/- 7 beats/min), whereas changes in catecholamine and insulin concentrations did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596601 TI - Plasma norepinephrine in humans: limitations in assessment of whole body norepinephrine kinetics and plasma clearance. AB - To investigate catecholamine residence in plasma, constant intravenous infusions of increasing duration (20, 40, and 80 min) of [3H]norepinephrine [( 3H]NE), [3H]isoproterenol [( 3H]IP) IP) and a reference substance: 131I-labeled hippurate were performed in six normal volunteers. In contrast to [3H]IP and 131I hippurate, whole body clearance from plasma of [3H]NE, as obtained from infusion rate divided by plasma concentration of tracer [1.74 +/- 0.64 (SD) 1/min] was significantly higher than the value obtained by total tracer infusion divided by total plasma area of tracer (1.27 +/- 0.51, P less than 0.01). Mean residence time in plasma (theta) after stopping the infusion of [3H]NE increased along an almost straight line with progressive infusion time, theta of 131I-hippurate increased less, and constant values were recorded after 40 min infusion of [3H]IP. Our results suggest the presence of a very large (cellular) pool from which a reversible transport of [3H]NE back into plasma takes place. The plasma clearance of tracer NE, as determined from infusion rate and plasma concentration of tracer, includes transport to and accumulation in this large store. Thus the "final metabolic clearance," reflecting irreversible removal of NE, is smaller than previously estimated due to recycling through the plasma space. Attention has been drawn to limitations of [3H]NE kinetics. PMID- 2596602 TI - Growth hormone directly stimulates gluconeogenesis in canine renal proximal tubule. AB - To characterize the action of growth hormone (GH) on gluconeogenesis in renal proximal tubule, glucose production was measured in suspensions of canine renal proximal tubular segments incubated with 1 mM L-alanine, 10 mM lactate, 1 mM succinate, and various concentrations (10(-11) to 10(-6) M) of recombinant bovine GH (bGH). Production of glucose increased as a function of time for 120 min. Bovine growth hormone (10(-6) M) increased glucose production at 120 min by 55 +/ 16%. Significant enhancement of glucose production occurred in suspensions of segments incubated with as little as 10(-10) M bGH. Half-maximal stimulation occurred at between 10(-9) and 10(-8) M. To ascertain whether these actions of bGH are mediated directly, we determined the effects of insulin-like growth factors (IGFs) I and II on glucose production. Addition of IGF-I to segments enhanced glucose production in a concentration-dependent manner. However, incubation with bGH did not induce measurable IGF-I production in the segments. In contrast to the action of IGF-I, IGF-II did not affect glucose production. We conclude that bGH acts directly on cells within proximal tubular segments to enhance gluconeogenesis. Stimulation of gluconeogenesis in vitro could reflect a counterregulatory action of GH exerted on renal proximal tubule in vivo. PMID- 2596603 TI - Modeling thyroxine transport to liver: rejection of the "enhanced dissociation" hypothesis as applied to thyroxine. AB - Three models for the hepatic uptake of thyoxine (T4) from human plasma were considered: 1) uptake occurs exclusively via the pool of free T4 after spontaneous dissociation of T4-plasma-protein complexes, 2) uptake occurs primarily via the pool of bound T4 by the interaction of one or more binding proteins with the cell-surface membrane, and 3) uptake occurs primarily by "enhanced dissociation" of T4 from one or more of its binding proteins within the sinusoids. Each of these models was examined in relation to well-accepted unidirectional uptake and steady-state kinetics data that indicate that 1) between 4 and 24% of the T4 in normal human serum is taken up unidirectionally by the liver in a single pass, and 2) the in vivo disposal rate of T4 is unaffected by primary changes in the plasma concentration of thyroid hormone-binding globulin. Both analytical and numerical techniques were used. The first two models were found to be compatible with both the steady-state kinetics data and the unidirectional uptake data, given certain assumptions in each of the models. Although theoretically distinguishable on the basis of unidirectional uptake data, uncertainty over the true uptake (influx) rate constant for free T4 prevented resolution between these two models. In contrast, the third model, that of enhanced dissociation [W. M. Pardridge, Am. J. Physiol. 252 (Endocrinol. Metab. 15): E157-E164, 1987], was found, as currently formulated with respect to T4, to be incompatible with both the steady-state kinetics data and the unidirectional uptake data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596604 TI - Leukocyte adherence to venular endothelium during ischemia-reperfusion. AB - Xanthine oxidase-derived oxidants and leukocytes have been implicated in the microvascular injury associated with reperfusion of ischemic intestine. The objective of this study was to determine whether xanthine oxidase-derived oxidants play a role in the leukocyte-microvascular interactions initiated by ischemia-reperfusion. Adherence and extravasation of leukocytes were monitored in cat mesenteric venules subjected to 1 h of ischemia (blood flow reduced to 20% of control) and reperfusion. Leukocyte rolling velocity, vessel diameter, and red cell velocity were also measured in control (untreated) animals and in animals pretreated with either allopurinol or superoxide dismutase. The responses of venular blood flow, wall shear rate, and leukocyte rolling velocity to ischemia and reperfusion did not differ between the three experimental groups. In control animals, 1 h of ischemia was associated with significant adherence and extravasation of leukocytes with reperfusion greatly enhancing these responses. Allopurinol treatment did not alter the responses to ischemia per se, yet it largely prevented the further increment in adherence and extravasation associated with reperfusion. Superoxide dismutase treatment attenuated the leukocyte responses elicited by both ischemia and reperfusion. Our observations that both allopurinol and superoxide dismutase attenuate reperfusion-induced leukocyte adherence and extravasation are consistent with the hypothesis that xanthine oxidase-derived oxidants initiate the leukocyte infiltration induced by reperfusion of ischemic intestine. PMID- 2596605 TI - Origin of regional and species differences in intestinal glucose uptake. AB - Differences in intestinal absorption among physiological states, intestinal regions, and animal species could arise from many anatomical factors (e.g., intestinal length and diameter, or area amplification by villi and microvilli) and biochemical factors (e.g., transporter density and turnover number). In no comparison had all these factors been measured. Hence we made the necessary new measurements to identify the origin of differences in glucose absorption among three species (mouse, desert wood rat, and desert iguana) and among three intestinal regions in two of these species. Turnover numbers range from 6,900 to 32,300 glucose molecules per minute per site. Microvilli amplify intestinal area by a larger factor (36-96 times) than do villi (2-14 times), so that the intestine's actual area is at least 110-1,280 times the nominal area of the equivalent smooth-bore cylinder. Species comparisons among mammals yield the striking result that the area of the whole length of the small intestine at the microvillus level varies nearly linearly as the mammal's metabolic live mass. For the species studied, all the anatomical and biochemical factors studied proved to make significant contributions to species and regional difference in glucose uptake. PMID- 2596606 TI - Gastric response to mucosal IgE-mediated reactions. AB - The effect of immunoglobulin E (IgE)-mediated anaphylaxis has been extensively studied in the small intestine, but little information is available on the response of the stomach to IgE-mediated mucosal reactions to food proteins. The effect of luminal antigenic challenge on gastric acid secretion, gastric emptying, and mucosal mast cell degranulation was examined in rats sensitized to egg albumin or in sham-treated controls. Intraluminal challenge of the stomach with egg albumin in sensitized animals significantly increased gastric acid secretion and delayed gastric emptying. The response was specific for the sensitizing antigen as challenge with bovine serum albumin was without effect. Sham-treated animals showed no response to egg albumin or bovine serum albumin. The increase in gastric acid secretion was reproduced by antigen challenge in naive animals passively transferred with hyperimmune serum. This effect was abolished by prior heat treatment of the serum. In sensitized animals challenged with egg albumin, there was histological evidence of mast cell degranulation in the stomach mucosa, increased intraluminal release of histamine, and increased serum levels of rat mast cell protease II, a marker specific for mucosal mast cell degranulation. The findings indicate that the stomach is a target organ for IgE-mediated reactions to food proteins. Antigen challenge in sensitized animals leads to increased gastric acid secretion and delayed emptying and evidence of mucosal mast cell activation. PMID- 2596607 TI - Deoxycholate-stimulated release of peptide YY from the isolated perfused rabbit left colon. AB - The purpose of this study was 1) to measure the effect of graded concentrations of oleic acid and deoxycholic acid (DCA) on the release of peptide YY (PYY) and enteroglucagon and 2) to test whether DCA-stimulated release of PYY was neurally mediated by blocking neuronal conduction with tetrodotoxin. Studies were performed in isolated left colons from New Zealand White rabbits. Oleic acid in concentrations from 0.22 to 22 mM suspended in 10 mM DCA significantly stimulated release of PYY (P less than 0.01) but resulted in no graded response (Bartlett's test, P = 0.15). Similarly, oleic acid (2.2 mM) suspended with ursodeoxycholic acid (10 mM) produced no increased release of PYY above that achieved by ursodeoxycholic acid alone. In contrast, oleic acid (2.2 and 22 mM suspended with 10 mM DCA) produced a graded release of enteroglucagon during the stimulated period. Deoxycholic acid caused a concentration-dependent release of PYY (1, 3.3, 10, and 25 mM) during the stimulated period. Deoxycholic acid (1 and 10 mM) did not significantly increase enteroglucagon release. Tetrodotoxin blockade had no effect on release of PYY stimulated by 10 mM DCA. Because PYY and enteroglucagon are both found in colonic endocrine cells, these results suggest that the release of PYY and enteroglucagon are mediated by specific secretagogues and not simply caused by noxious effects of the agonists. Also, this study has demonstrated that DCA-stimulated release of PYY is not dependent on neuronally mediated mechanisms. PMID- 2596608 TI - Opening mechanisms of the human upper esophageal sphincter. AB - Our goals in this study were to evaluate the mechanisms operative in swallow associated opening of the upper esophageal sphincter (UES) and to determine the dynamics of fluid flow across the sphincter. For this purpose, we obtained concurrent videofluorographic and manometric studies of 2- to 30-ml barium swallows in 15 normal subjects. We found that the resting UES high-pressure zone corresponded closely with the location of the cricopharyngeus. The findings indicated that manometric UES relaxation and anterior hyoid traction on the larynx invariably preceded UES opening. With graded increases in bolus volume, progressive increases occurred in UES diameter, cross-sectional area, flow duration, and transsphincteric flow rate. Intrabolus pressure upstream to the UES and within the UES at its opening during transsphincteric flow of barium remained within a narrow physiological range of less than 10 mmHg up to a bolus volume of 10 ml. With increases in bolus volume, anterior hyoid movement, UES relaxation, and UES opening occurred sooner in the swallow sequence to accommodate the early entry of large boluses into the pharynx. We conclude that during swallowing 1) normal UES opening involves sphincter relaxation, anterior laryngeal traction, and intrabolus pressure, 2) volume-dependent adaptive changes in UES dimension accommodate large bolus volumes and flow rates with minimal requirement for increases in upstream, or intrasphincteric, intrabolus pressure or UES opening duration, and 3) volume-dependent changes in UES dimensions as well as timing of UES relaxation and opening indicate a sensory feedback mechanism that modulates some components of the swallow response generated by the brain stem swallow centers. PMID- 2596609 TI - Vitamin D3 and glucose-6-phosphate dehydrogenase in rat duodenal epithelial cells. AB - A microdensitometric method was employed to determine enzyme activities in situ in undisrupted tissue rat duodenum. The effect of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] on glucose-6-phosphate dehydrogenase (G6PD) activity and on the two utilization pathways of synthesized NADPH, H1 (mixed function oxidation) and H2 (biosynthesis), was studied. In normal animals, a crypt-to-villus gradient of G6PD activity and of both NADPH utilization pathways was observed. A high level of NADPH utilization occurred predominantly via the H2 pathway. In vitamin D deficient rat animals, G6PD activity in the middle part of the villus was approximately 60% lower than in normal animals [10.05 +/- 0.35 vs. 3.95 +/- 0.26 (means +/- SE) A585.min-1.micron-3 X 10(5), P less than 0.001] with reduced NADPH utilization via the H2 pathway (8.39 +/- 0.49 vs. 2.73 +/- 0.43 A585.min-1.micron 3 X 10(5), P less than 0.001) but not the H1 pathway (1.65 +/- 0.17 vs. 1.22 +/- 0.19 A585.min-1.micron-3 X 10(5), P = NS). Intraperitoneal administration of 1,25(OH)2D3 (500 pmol) to vitamin D-deficient animals resulted in increased G6PD activity within 30 min (4.09 +/- 0.38 vs. 5.51 +/- 0.39 A585.min-1.micron-3 X 10(5), P less than 0.05), attaining normal levels within 2 h. The H2 but not the H1 pathway of NADPH utilization increased significantly in response to 1,25(OH)2D3. This increase is essentially located in the basal and middle parts of the villus. Thus 1,25(OH)2D3 may influence biosynthesis in the duodenum via stimulation of G6PD activity and the H2 pathway of NADPH utilization. PMID- 2596610 TI - Rapid frequency rhythmic postprandial motility in the canine ileum. AB - We report here a novel motor phenomenon that we recorded from the canine terminal ileum in the postprandial period. In chronic models that allowed us to monitor myoelectrical activity and intraluminal pressure from the jejunum and distal ileum, we regularly saw in the ileum, but not in the jejunum, a rhythmic sequence of intraluminal pressure waves at a frequency of 19-24 cycles/min. This unusual motor pattern was rarely seen in the first 2 h after food and was essentially absent during fasting; it appeared reproducibly 1-4 h after food, at the time when chyme reached the ileum. The phenomenon was accompanied by spike bursts that were usually at the same rapid, rhythmic frequency, but the rate of the ileal slow wave persisted at the preprandial level (13-15/min). These findings further exemplify differences in the regulation of the motility between jejunum and ileum; moreover, the phenomenon highlights the capacity of the distal small intestine to response specifically to the nature of its luminal contents. This reaction of the ileum to the arrival of dietary residues is deserving of further study in the evaluation of the small bowel's response to a meal. PMID- 2596611 TI - Protein-lipid interactions in human small intestinal brush-border membranes. AB - Brush-border membranes prepared from proximal and distal human small intestine were characterized with respect to lipid fluidity, lipid composition, and protein lipid interactions. Steady-state fluorescence polarization and differential polarized phase fluorometry revealed that the "static" and "dynamic" rotational components of fluidity (assessed by r infinity values of 1,6-diphenyl-1,3,5 hexatriene and r values of 12-anthroylstearate, respectively) were greater in the distal membranes compared with their proximal counterparts. The lipid fluidity of distal brush-border membranes was also greater as measured by excimer/monomer fluorescence ratio intensities of pyrene decanoate. A lower molar ratio of cholesterol/phospholipid in the distal membranes was responsible for these regional fluidity differences. Lipid thermotropic transitions were detected at 26 28 degrees C using 1,6-diphenyl-1,3,5-hexatriene in proximal and distal membranes. Arrhenius plots of p-nitrophenylphosphatase and gamma-glutamyl transpeptidase activities demonstrated breakpoints in the vicinity of the lipid thermotropic transition temperatures (28-30 degrees C), whereas maltase and sucrase yielded a single activity slope over the range of 10-40 degrees C. Moreover, 50 mM benzyl alcohol fluidized proximal brush-border membranes and increased p-nitrophenylphosphatase activity in this membrane. This agent also shifted the phase transition temperature of the membrane and breakpoint temperature of this enzymatic activity from approximately 28 degrees C to 19 degrees C. These findings demonstrate that differences in human small intestinal brush-border membrane lipid fluidity and lipid composition exist between proximal and distal regions of this organ. Furthermore, alterations in fluidity and/or lipid composition modulate p-nitrophenylphosphatase and gamma-glutamyl transpeptidase but not sucrase or maltase activities in these membranes. PMID- 2596612 TI - Effects of quinacrine on calcium active transport by rat intestinal epithelium. AB - To determine the possible role of acidic lysosomal vesicles in the transcellular transport of Ca, bidirectional Ca fluxes were measured across intestinal segments in vitro in the absence of electrochemical gradients. Mucosal addition of the weak base quinacrine (0.2 mM) caused a 67% decline in the mucosal-to-serosal Ca flux (Jm----s) across duodenum (175 +/- 34 vs. 58 +/- 9 nmol.cm-2.h-1, P less than 0.007) and reduced cecal Ca Jm----s (177 +/- 15 vs. 45 +/- 4, P less than 0.0001). Higher concentrations of up to 2.0 mM caused no further decline in cecal Ca Jm----s. Inhibition of cecal Ca Jm----s by mucosal chloroquine (0.1 mM) or ammonium chloride (10 mM) varied from 37 to 50%. Addition in vitro of quinacrine to enterocyte basolateral membrane vesicles failed to inhibit ATP-dependent Ca uptake. The present studies demonstrate that agents that collapse lysosomal pH gradients inhibit transcellular Ca transport. These observations are consistent with the hypothesis that Ca destined for transcellular transport is functionally associated with acidic lysosomes and that these organelles play an important role in transepithelial Ca translocation. PMID- 2596613 TI - Colonic motor response to a meal in dogs. AB - We investigated the effects of ingestion of a meal on colonic motor activity in six conscious dogs, each instrumented with seven strain-gauge transducers to record circular muscle contractions. A 1,300-kcal meal was given after a 4-h control recording. The post-prandial period of 8 h was subdivided into an early period lasting 2 h and a late period lasting 6 h. The ingestion of the meal did not disrupt the colonic migrating myoelectric complexes (CMMCs) but prolonged their cycle length in the early postprandial period. The cycle length was not different from the control during the late postprandial period. The mean and total duration of contractile activity per hour increased significantly during the early postprandial period in the distal colon but not in the proximal or the middle colon. During the late postprandial period the mean and total duration of contractile activity per hour increased significantly throughout the colon. Giant migrating contractions occurred rarely during the 8-h postprandial period. We conclude that different parts of the colon respond to the ingestion of a meal in different ways. The response also depends on whether the fresh digesta has reached the colon. The late postprandial response is likely to be due to the entry of fresh digesta into the colon. PMID- 2596614 TI - Accumulation of weak base in gastric mucosa provides evidence for an acidic storage compartment. AB - Uptake and release of acridine orange (AO), a fluorescent weak base that accumulates in acidic spaces, were studied in perfused frog gastric mucosa. Tissue was mounted between two flow-through chambers and loaded with AO on the mucosal side. AO washout and acid secretion rate were monitored simultaneously by a flow-through fluorescence detector and a pH-stat, respectively. Data were displayed on a computer screen, stored, and analyzed. AO, in concentrations as high as 0.02 mM, does not affect the acid secretion rate. Nonlinear least-squares analysis of AO washout curves resolved two exponential components: a faster component associated mainly with AO washout from the chamber and a slower component reflecting primarily AO washout from the tissue. The slower exponential declines more slowly at higher concentrations and/or longer duration of AO loading, whereas the faster exponential is unaffected. AO washout is unaffected by the level of the steady-state acid secretion rate. Nitrite inhibits the acid secretion rate but does not affect the AO washout. When nitrite is removed, acid secretion rate and fluorescence (AO concentration in the mucosal medium) increase simultaneously and transiently. The net amount of AO released from the tissue is proportional to the net amount of acid released. Stimulation by secretagogue in basally secreting tissue causes synchronous transient increases in acid secretion rate and fluorescence. We conclude that accumulation of AO provides evidence for the existence of an intracellular storage pool of free protons within the transporting epithelium. PMID- 2596616 TI - Modulation of environmental reinstatement effects through encoding strategies. PMID- 2596615 TI - Recency and suffix effects as a function of auditory confusability and set size. PMID- 2596617 TI - Changes seen in lymph nodes draining the sites of large joint prostheses. AB - We report the histological findings seen in the lymph nodes draining the sites of large joint prostheses. Two patients underwent multiple prosthetic joint replacements. In one patient, the regional lymph nodes were enlarged during the revision of a total hip prosthesis, and a representative lymph node was resected. The other patient had undergone a pelvic lymph node dissection as part of a staging procedure for prostatic carcinoma. By light microscopy, the lymph nodes from both patients showed markedly dilated nodal sinuses filled with macrophages containing abundant eosinophilic, PAS-positive, granular material. Polarization microscopy revealed needle-like particles within the cytoplasm of the macrophages. We believe that the histological appearance of the lymph nodes represents a florid foreign body reaction to fragments of polyester or polyethylene derived from the articulating surfaces of the joint prostheses and transported to the regional lymph nodes via the lymphatic circulation. Sinus histiocytosis seen in the lymph nodes draining the sites of joint prostheses may resemble, and must be distinguished from, other conditions invoking a sinus pattern of lymphadenopathy, as well from benign and malignant diseases that involve the lymph nodes in a pattern mimicking sinus histiocytosis. PMID- 2596618 TI - Aggressive bladder carcinoma in an adolescent. Report of a case with immunohistochemical, cytogenetic, and flow cytometric characterization. AB - Malignant bladder neoplasms of urothelial origin are rare among children; fewer than 125 cases have been reported. Typically, these tumors are single papillary lesions of low grade and stage that have an excellent prognosis following surgical excision. A grade III transitional cell carcinoma of the bladder occurred in a 14-year-old boy who had no urinary tract malformation, carcinogenic exposure, or family history of cancer. Immunohistochemical stains of the tumor were positive for cytokeratin and high-molecular-weight keratin. The tumor tissue failed to stain with an antibody to the patient's blood group [anti-ABO(H)] but was positive for the Thomsen-Frieden-reich antigen. Flow cytometry of the tumor cells demonstrated a diploid or near-diploid DNA content. A karyo-type of the tumor showed a modal chromosome number of 46 with one reciprocal translocation between chromosomes 17 and 22 and a nonreciprocal translocation between chromosomes 18 and 22. The tumor was unique because of its highly aggressive nature and its diploid chromosome number. This case represents the first indepth characterization of a transitional cell carcinoma in a pediatric patient by flow cytometry and cytogenetics, as well as a variety of immunohistochemical studies including ABO(H) blood group and Thomsen-Freidenreich antigens. PMID- 2596620 TI - Invasion in lung cancer. PMID- 2596619 TI - Immunohistochemistry in bone marrow diagnosis. PMID- 2596621 TI - Thyroid cysts. PMID- 2596622 TI - Epithelioid hemangioendothelioma of liver. Clinicopathological correlation of 10 cases treated by orthotopic liver transplantation. AB - We present a review of the clinicopathologic features of a series of 10 patients with hepatic epithelioid hemangioendothelioma treated by orthotopic liver transplantation. This tumor has an unpredictable prognosis. Morphological features predictive of biological behavior were not identified in these patients. It appears that metastatic spread at the time of surgery is not a significant contraindication to surgery and has no correlation with survival. Nine patients are alive (5-134 months), five disease free and four with tumor. The etiology of this tumor is unknown. However, there is an association of oral contraceptive use with this tumor in four (66%) of the six female patients in this series and in 37% of such reported cases. PMID- 2596623 TI - Calcium gradients in inner ear endolymph. AB - Recent studies suggest that endolymphatic hydrops resulting from the ablation of the endolymphatic duct and sac in guinea pigs may be caused by a disturbance of endolymph calcium homeostasis. A similar disturbance of calcium homeostasis could represent the underlying cause of Meniere's disease. In this study, we mapped the calcium concentrations and electrical potentials throughout the endolymphatic system in normal guinea pigs. Large concentration differences exist between different compartments, including a more than twofold increase along the length of the cochlea. The electrochemical potential for calcium (the force driving passive longitudinal calcium movement) was calculated for all the endolymphatic compartments. The results show that endolymph is extremely inhomogenous with respect to calcium potentials. On the basis of these potentials, it appears that calcium is transported into endolymph in the cochlea and out of endolymph in the saccule and utricle. The possibility that endolymphatic hydrops arises from a disturbance in longitudinal flow of calcium, rather than in longitudinal volume flow, is considered. PMID- 2596624 TI - Eighth nerve signs in a case of multiple sclerosis. AB - We evaluated a 25-year-old woman with multiple sclerosis who presented with the acute onset of a profound unilateral high-frequency, sensorineural hearing loss that resolved clinically within 10 days. Click-elicited brain stem-evoked responses were abnormal at the time of presentation and demonstrated only limited recovery over a follow-up period of 11 months. Magnetic resonance imaging disclosed a lesion in the eighth nerve root-entry zone and the cochlear nucleus. Our findings in this case support the hypothesis of eighth nerve root-entry zone involvement in sudden hearing loss in multiple sclerosis and reinforce the notion that click-elicited brain stem-evoked responses are useful primarily to evaluate the high-frequency regions of the auditory system. PMID- 2596625 TI - The preparation of acetic acid for use in otic drops and its effect on endocochlear potential and pH in inner ear fluid. AB - The ototoxicity of an otic drop preparation containing 2% acetic acid and 3% propylene glycol (VoSol, Denver Chemical Co., Humacao, PR) was investigated according to measurements of endocochlear potential (EP) and inner ear fluid pH. The application of this preparation to the round window membrane for 30 minutes caused a depression in EP from 80.5 +/- 2.5 mV (mean +/- SD; n = 6) to 11.7 +/- 7.7 mV, and lowered inner ear fluid pH from 7.55 +/- 0.09 to 5.06 +/- 0.19 (n = 6) in perilymph and from 7.52 +/- 0.07 to 5.88 +/- 0.63 (n = 6) in endolymph. Two percent acetic acid produced similar changes after 30 minutes: EP was reduced from 83.0 +/- 2.2 mV to 34.0 +/- 2.9 mV and endolymphatic pH from 7.49 +/- 0.04 to 6.83 +/- 0.21 (n = 4). However, the application of artificial perilymph of pH 4 titrated with HCl induced no significant changes in either EP or endolymphatic pH. We suggest that the mechanisms of ototoxicity in the otic drop preparation are Na+ and K+-ATPase inhibition, and that such inhibition is due to the intracellular acidification of strial cells resulting from the penetration of acetic acid across the cell membrane, and to the direct and synergistic actions of propylene glycol. PMID- 2596626 TI - Turnover of sulphated macromolecules in the murine endolymphatic sac after long term kanamycin treatment. AB - Radioactively labeled sulphur was injected into 12 mice of the NMRI strain 20 days after pretreatment with kanamycin. The animals were decapitated after intervals ranging from 2 minutes to 24 hours after injection. After a routine autoradiographic procedure, darkly stained silver grains were detected in the endolymphatic sac (ES) and its surroundings. One hour after injection, the grains were found in the surrounding blood vessels. Eleven hours later, maximal uptake was seen in the epithelial cells of the ES in the kanamycin-treated animals. Twenty-four hours after injection, a faint S35 uptake in the ES could still be detected. An increase in the ES activity, indicated by an increased number of free-floating cells and the secretion of a sulphur-containing intraluminal substance, did not occur. The spreading pattern of sulphur, as shown in this investigation, does not support the theory that waste products from the inner ear, transported to the ES by the longitudinal flow, produces an increased activity in the sac after long pretreatment with kanamycin. In 12 control animals, no difference in the distribution of labeling was observed, but there was an additional uptake in the free intraluminal cells which was not seen in the kanamycin group. PMID- 2596628 TI - Clinical radiology quiz. Branchial cleft cyst. PMID- 2596627 TI - Endolymphatic hydrops after fenestration: a temporal bone study with implications on the function of the utriculo-endolymphatic valve. AB - A temporal bone specimen demonstrating endolymphatic hydrops 13 years after fenestration of the lateral semicircular canal is presented. Fibro-osseous tissue extending from the lateral semicircular canal and reaching the vestibule produced fixation of the membranous wall of the utricle to the bony wall. Fixation and retraction of the utricule appears to have resulted in a permanently open utriculo-endolymphatic valve leaflet. Similar findings of fibro-osseous changes arising from the area of the crus commune and an open valve were found in a Meniere's disease specimen. The implications of these findings on the function of the valve are discussed. PMID- 2596629 TI - Temporal bone histopathology: residents' quiz. Tuberculous otitis media. PMID- 2596630 TI - [Tissue pO2 and fetal heart activity during induction of labor with oxytocin]. AB - A total of 65 women in labor complicated with uterine inertia were investigated for tissue pO2 and cardiac performance of fetuses under the effect of oxytocin. The authors stated that the aggravation of fetal status in drug-induced labors resulted from poorer tissue oxygenation caused by the activation of uterine contractility. In this line, hypoxic changes of the fetus were more pronounced in pregnancies complicated by nephropathy or prolonged pregnancy. Accurate monitoring of the fetal status and the character of induced labor course was found to be mandatory. Before oxytocin induction the fetus should be protected with diazepam. PMID- 2596631 TI - [Ultrastructural damage of the fetal kidneys in generalized decompensated maternal thrombogenesis]. AB - In the experiments on 40 pregnant white rats, the authors used electron microscopy for the assessment of structural renal changes in the dams and their fetuses, which had occurred in generalized decompensated thrombogenesis resulted from massive heterohemotransfusion. The common coagulative origin was established for the lesions in dams and fetuses, which appeared as disseminated microthrombosis, degenerated interstitial connective tissue and cell structures. PMID- 2596632 TI - [Placental scintigraphy--a diagnostic method for evaluating indications for hyperbaric oxygenation in pregnant women with high risk of perinatal pathology]. AB - At most, 40 pregnant females at a high risk for fetal perinatal pathology underwent clinical investigation, ultrasonic scanning of the placenta, recording of the fetal electro- and phonocardiography, the evaluation of the placental levels of lactogen and estradiol and thermoresistant alkaline phosphatase changes of the values considered who were then treated with hyperbaric oxygenation (HBO) under the control of dynamic placental scintigraphy. Based on the placentographic findings, the authors distinguished from the whole of the risk-group the patients whose pattern of uteroplacental blood flow response to the treatment was beneficial and therefore the HBO treatment for fetoplacental insufficiency was advisable. PMID- 2596633 TI - [Disputed problems in perinatal medicine]. PMID- 2596634 TI - [Characteristics of placental development in multiple pregnancy]. AB - Based on the morphological and clinical investigations, the authors defined various placental structures of 68 females with multiple pregnancies. The correlation between the structure of the placenta and the type of the prenatal development of the fetuses was established. PMID- 2596636 TI - [Nature and mechanism of hemodynamic changes in fetuses of mothers with various types of diabetes mellitus]. AB - Doppler echocardiography of flow in the fetal aorta and the umbilical artery as well as fetal echocardiography performed in 61 pregnant females with diabetes mellitus revealed central intracardiac hemodynamic alterations as risk factors for the development of "diabetic" heart failure in newborns. Pregnancy- associated diabetes patients and females with diabetes of type I demonstrated a somewhat decrease in the fetal myocardial contractility which was evidently determined by metabolic alterations in the myocardium, macrosomia and disorders in the fetoplacental circulation. PMID- 2596635 TI - [Changes in cardiotocographic indicators in fetal hypotrophy]. AB - The investigation of 220 females with the third trimester of pregnancy revealed that ++cardiotocographic values naturally varied with developing fetal hypotrophy. For instance, hypotrophy, stage I, corresponded, as a rule, to the initial manifestations of fetal chronic disorders whereas hypotrophy, stages II and III, corresponded to the moderate and, occasionally, severe health status. PMID- 2596637 TI - [Homocarnosine of the amniotic fluid as an indicator of fetal cerebral lesions]. AB - The authors stated the correlation between the levels of homocarnosine in the amniotic fluid, fetal encephalopathy and the degree of fetal neurologic symptomatology. PMID- 2596638 TI - [Clinico-morphologic changes in the feto-placental complex in neonatal pathology]. AB - Organs of newborns expired in the early neonatal period were studied as were histological, histochemical and ultrastructural alterations in the placentas of fetuses with a history of chronic intrauterine hypoxia (45 cases). The findings compared with the similar investigations conducted in the females with physiological pregnancy and labor were suggestive of the interrelation of placental alterations and structural lesions in the liver and myocardium of the newborn. PMID- 2596639 TI - [Status of the fetus and placental function in women with viral and Mycoplasma infections]. AB - Females with viral and Mycoplasma infection were studied for the fetal and placental status. There was fetal growth retardation; disorders in fetal cardiac performance; placental dysfunction appeared as decreased levels of placental lactogen, chorionic gonadotropin, appeared signs of placental aging, decreased blood flow. PMID- 2596640 TI - [Value of echoencephalography in the diagnosis of periventricular leukomalacia in children and the prognosis of their development]. AB - The investigation was conducted to reveal reliable echographic features of early (necrotic) stages of periventricular leukomalacia (PVL) on the basis of retrospective analysis of echograms of decreased children (with postmortem diagnosis of PVL) and survived newborns with pronounced cystic changes in the periventricular areas (advanced PVL stage), which were revealed during dynamic echoencephalography. Altogether 268 echograms of 78 children with a birth-weight from 700 to 2400 g were analysed. All children but one were born preterm. Ultrasound device "Aloka-SSD 118" (Japan), with a transducer frequency of 5mHz, was used during frontal fontanel echoencephalography. Three patterns of echographic image of periventricular areas compromised with the aforementioned disease were identified. In the detection of early PVL stages, the specificity of the technique was 94% and sensitivity, 86%. The followup that lasted from 9 months to 2.5 years revealed varying pronounced neurologic disorders in all the survived children with PVL. PMID- 2596641 TI - [The role of prostaglandins in pathogenetic mechanisms of the respiratory distress syndrome in premature newborn infants]. PMID- 2596642 TI - [Lipid composition of placental mitochondria in pregnant women with anemia]. PMID- 2596643 TI - [Treatment of the umbilical cord stump with acetylsalicylic acid as a measure to prevent suppurative septic diseases]. PMID- 2596644 TI - [Use of levamisole in inflammatory diseases of the uterus and adnexa uteri]. PMID- 2596645 TI - [Use of dropper retrograde hydrotubation in the rehabilitation of patients after plastic surgery of the fallopian tubes]. PMID- 2596646 TI - [Results of discussions on the problem of gestoses]. PMID- 2596647 TI - [Substantiation of complex measures in the prevention of bacterial infections in newborn infants]. PMID- 2596648 TI - Renovascular hypertension and demyelimating disease in a young woman. AB - Renal artery stenosis is an uncommon, but curable cause of systemic hypertension. The most common causes of stenosis are atherosclerosis, and fibromuscular dysplasia. Diagnosis may be difficult due to the lack of a suitable screening test, and a high index of suspicion needs to be maintained. Treatment may be with pharmacotherapy, renal angioplasty, or surgery and the choice of therapy needs to be tailored to the individual patient. Once a stenotic lesion is discovered in a hypertensive patient, the functional significance is not always clear cut. Fibromuscular dysplasia may be a systemic disease in some cases, and may affect the central nervous system. PMID- 2596649 TI - Results of an indoor air pollution investigation. AB - After the opening of a new elementary school in fall 1986, several members of the school's staff noticed symptoms they attributed to the workplace. An investigation by the Occupational Safety and Health Branch (OSHA) of the Alaska Department of Labor found no major health problems and concluded that fireproofing at the school may have caused a petroleum-like odor. In fall 1987, parents reported illness in their children that they attributed to school attendance. Subsequent epidemiologic investigation found that student and staff absentee rates were not increased and were similar to other schools in the district. Testing conducted by the National Institute for Occupational Safety and Health (NIOSH) confirmed that the petroleum-like odor was due to the fireproofing. Toxicologic information and the results of air sampling confirmed that no adverse health effects would be expected from the product. By working together with NIOSH, OSHA, the school district, and a consulting mechanical engineer, deficiencies in the school's ventilation system were discovered and immediately corrected with interim engineering changes. Only by bringing multiple agencies together and openly sharing findings with concerned parents and staff were the problems at the school resolved. PMID- 2596650 TI - Humana Hospital Air Ambulance program improves acute care access. PMID- 2596651 TI - Infusions of analgesics, sedatives and muscle relaxants in patients who require intensive care. PMID- 2596652 TI - The detection of intra-operative myocardial ischaemia. Preliminary experience with the right-sided precordial lead. AB - The value of monitoring the right precordial lead, V4R, to detect peri-operative ischaemic events during coronary artery surgery was studied in 60 patients. Thirty-four patients had only left-sided coronary disease (Group 1). The other 26 patients had both left-sided occlusive coronary artery disease and significant right-sided occlusive lesions on coronary angiography (Group 2). Lead sensitivity was estimated, assuming that all ST segment changes were true positive responses. Sensitivity using a single lead was greatest for lead V5 in the two groups (73% for Group 1 and 69% for Group 2). Sensitivity in Group 1 for lead II was intermediate (55%), whereas sensitivity for lead V4R was only 9%. In Group 2, on the other hand, lead V4R was 54% sensitive and lead II only 31%. The combination of leads V4R and V5 increased the sensitivity to 92% in Group 2, whereas lead II or V5 combined with V4R failed to improve sensitivity in Group 1. The monitoring of lead V4R allowed detection of 23% of the ischaemic episodes in Group 2 that would have passed undetected if only lead II and V5 were monitored. These results demonstrate the value of an additional right precordial lead during coronary artery bypass grafting in patients with right-sided occlusive disease. PMID- 2596653 TI - Pupillary signs during cardiac surgery. Their use in the prediction of major cerebral deficit following cardiopulmonary bypass. AB - Pupil sizes and reactions to light were studied in 100 patients who had cardiopulmonary bypass. Behaviour of the pupils was observed at six stages during the operation. Most patients (71) had pupils of equal size and similar reaction to light at all times. Twenty-three patients developed unequal pupils at some stage, while six had equal pupils throughout but exhibited differing reaction to light. Major cerebral deficit was significantly more common after operation in patients who developed inequality in pupil size than those who did not (p less than 0.05). No relationship was seen between dissimilar pupil reaction to light and the development of neurological complications. The clinical estimation of pupil size may help to identify those patients who may exhibit postoperative major neurological dysfunction. PMID- 2596654 TI - Multidimensionality of psychological recovery from anaesthesia. Analysing six recovery tests. AB - Six recovery tests, choice reaction time (CRT), CRT doubletask, finger tapping test (FTT), critical flicker fusion frequency (CFF), Maddox wing, and p-deletion test, which cover basic cognitive, motor and perceptive functions as well as concentration, were analysed and compared with each other. Correlation between these tests after recovery from standardised general anaesthesia was calculated in 22 patients. Moderate to high correlation was found between CRT and CRT doubletask (r = 0.62 to r = 0.73), when parameters of six different tests were compared. Finger tapping correlated moderately with the movement time of both the CRT and the CRT doubletask (r = 0.46 and r = 0.47 respectively). We concluded that the CRT test, which measures initiation and movement time, might replace the CRT doubletask and the FTT. The CFF correlated moderately with the initiation time of the CRT doubletask, but because a slightly different function seems to be involved, further research is needed. Maddox wing and the p-deletion test correlated with no other test. Results indicated that recovery is differentiated in at least four distinct psychomotor functions, which should be tested by CRT (to measure initiation and movement time), Maddox wing and p-deletion. PMID- 2596655 TI - Intravenous regional analgesia with prilocaine for foot surgery. The effect of slow injections and high tourniquet inflation pressures. AB - Intravenous regional analgesia for foot surgery with an ankle tourniquet was used for 48 cases. Prilocaine 0.5% 3 mg/kg body weight was injected either quickly over about 2 minutes or slowly over about 5 minutes. The tourniquet was inflated either to occlusion pressure plus 100 mmHg or to occlusion pressure plus 200 mmHg. Plasma prilocaine levels were measured while the tourniquet remained inflated and after release of the tourniquet. All four techniques resulted in a low incidence and magnitude of prilocaine leak and low prilocaine plasma levels after tourniquet release. The data suggest that slow injection with the high tourniquet inflation pressure is better, although the differences in leakage with an intact tourniquet were not statistically significant. Excellent analgesia was achieved in over 90% of patients and there were no complete failures. No dangerously high prilocaine plasma levels were produced and no serious side effects observed. PMID- 2596657 TI - Chlormethiazole sedation for critically ill patients in renal failure. AB - Chlormethiazole infusions were used successfully to provide night sedation for 10 19 nights in three patients with renal failure managed by continuous veno-venous haemofiltration with dialysis. Fluid overload has accompanied the use of this drug previously because of its low concentration. The ability to remove large amounts of fluid during haemofiltration dialysis proved to be effective in preventing this. All three patients had impaired liver function and showed evidence of chlormethiazole accumulation after 4-6 days. The combination of progressive reduction in dose and daily withdrawal of infusions prevented a major problem. Acceptance of this technique by the patients was high. Chlormethiazole may be a useful addition to the drugs available to provide sedation in well defined clinical circumstances. PMID- 2596656 TI - Cardiovascular effects of fibrescope-guided nasotracheal intubation. AB - The cardiovascular effects of fibrescope-guided nasotracheal intubation were compared to those of a control group of patients who were intubated using the Macintosh laryngoscope. The 60 patients studied received a standard anaesthetic technique which included a muscle relaxant and were allocated randomly to one of two groups immediately before tracheal intubation. Systolic and diastolic arterial pressures in the fibreoptic group were significantly lower than in the control group during the first minute after intubation. The maximum increase in diastolic pressure was significantly lower in the fibreoptic group. The heart rate in the fibreoptic group was significantly higher than in the control group during all five minutes after intubation. The maximum increase in heart rate was significantly higher in the fibreoptic group. The cardiovascular responses to fibreoptic nasotracheal intubation under general anaesthesia should not cause undue concern in fit patients, but appropriate measures should be taken to prevent excessive tachycardia in compromised patients. PMID- 2596658 TI - A plea for noradrenaline. AB - Hypotension induced by nifedipine and chlorpromazine is discussed, together with the role of noradrenaline in the correction of this problem, which was resistant to other forms of therapy. PMID- 2596659 TI - Anaesthesia in an infant with Joubert's syndrome. AB - The presentation and management of a child with Joubert's syndrome is outlined with specific reference to the problems of opioid sensitivity and abnormal control of respiration. PMID- 2596660 TI - A disposable device for patient-controlled analgesia with fentanyl. AB - A disposable nonelectronic patient-controlled analgesia device was used to deliver fentanyl after upper abdominal surgery. Pain relief was satisfactory and plasma fentanyl concentrations were similar to those obtained by other workers who used electronic patient-controlled analgesia devices. PMID- 2596661 TI - An unusual emergence after total intravenous anaesthesia. PMID- 2596662 TI - Thoracic epidurals and general anaesthesia. PMID- 2596663 TI - An alternative to the oesophageal detector device. PMID- 2596664 TI - Comments on the oesophageal detector device. PMID- 2596665 TI - Unusual reaction to diclofenac. PMID- 2596667 TI - Analgesia for manipulation under anaesthesia after total knee replacement. PMID- 2596666 TI - General anaesthesia and the presence of the spouse. PMID- 2596668 TI - Bed rest after lumbar puncture is obsolete. PMID- 2596669 TI - Epidural infusion of bupivacaine-fentanyl during labour. PMID- 2596670 TI - Hypoxia during outpatient dental anaesthesia. PMID- 2596671 TI - Sticky labels to indicate hazard for anaesthesia. PMID- 2596672 TI - Cuff herniation. PMID- 2596673 TI - Is there liquid in the vaporizer? PMID- 2596674 TI - A prospective survey of anaesthetic critical events in a teaching hospital. AB - A survey of anaesthetic critical events based on voluntary anonymous reports was undertaken over a two and a half year period within a teaching hospital Department of Anaesthesia. At the end of the survey 167 reports were analysed. Human error was a contributing factor in 82% of events. Inadequate preoperative patient assessment or preparation, problems in the area of human/equipment interface and various stress factors for the anaesthetist featured significantly in the survey. The method enables the collection of objective data on factors contributing to anaesthetic and surgical risk and the formulation and evaluation of potential corrective strategies. It also facilitates harmonious peer review via individual and group feedback activities. The adoption of such a survey on a wider scale is seen as a valuable part of quality assurance in the continuing attempt to increase patient safety. PMID- 2596675 TI - Perioperative hypoxaemia detected by intermittent pulse oximetry. AB - Perioperative pulse oximetry was performed on one hundred consecutive abdominal surgical patients to audit our management of perioperative oxygenation. Oximetry was performed preoperatively, in the recovery room, and daily in the ward until discharge or the sixth postoperative day, with prescribed oxygen therapy continuing during measurement. Twenty-nine patients had saturations of 90% or less on a total of fifty-one occasions. Twenty-nine patients were prescribed prophylactic oxygen therapy, but seven had oxygen therapy stopped prematurely and were found to have saturations of 90% or less. In this group of patients, clinical assessment of oxygenation and the need for oxygen therapy was inadequate. Intermittent oximetry is rapidly and simply performed, and by detecting patients with arterial haemoglobin desaturation, could improve oxygen prescribing in the perioperative period. PMID- 2596676 TI - A controlled oximetric evaluation of inhalational, opioid and epidural analgesia in labour. AB - The effects on patient oxygenation of nitrous oxide, narcotic and epidural analgesia in labour were evaluated using pulse oximetry. Five groups of ten patients received either no analgesia (Control, Group 1), an epidural block alone (Group 2), nitrous oxide in oxygen alone (Group 3), intramuscular pethidine (Group 4), or nitrous oxide in oxygen combined with intramuscular pethidine (Group 5). Derived parameters included the maximum (MAX), minimum (MIN), average maximum (AV MAX), and average minimum (AV MIN) arterial haemoglobin oxygen saturation (SaO2), and differences between maxima and minima (MAX-MIN). There was a statistically significant difference between Group 1 and Group 5 for MIN, AV MIN and MAX-MIN SaO2 (P less than 0.05). All other groups showed no significant difference in any parameter when compared with the control group. The results are discussed with reference to normal and disordered maternal physiological changes in pregnancy. It is suggested that nitrous oxide should not be used for analgesia in labour where there is concern about maternal, placental or foetal reserve. PMID- 2596677 TI - Failure of intravenous infusions from extravasation and phlebitis. AB - A survey was done to compare the rates at which phlebitis and extravasation cause failure of intravenous infusions lasting more than 24 hours. Slightly more infusions failed due to phlebitis than to extravasation but extravasation did not occur earlier or later than phlebitis or differ significantly from it in frequency when different types of infusions were compared. Univariate life table analysis indicated that the co-infusion of blood, potassium or cephalosporin antibiotics slightly increased and that higher flow rates markedly increased failure, that infusions including continuous heparin and steroids had markedly decreased failure, and that failure was not significantly affected by other antibiotics or by differences in sex, age, location of infusion site or time of year. Multivariate analysis showed that the above differences were statistically significant only for infusion rate, heparin and steroids. PMID- 2596678 TI - Post-cholecystectomy pulmonary function following interpleural bupivacaine and intramuscular pethidine. AB - Twenty-four patients who were to undergo cholecystectomy were randomised into two groups, one to receive postoperative analgesia with interpleural bupivacaine, 20 ml of a 0.5% solution with adrenaline 5 micrograms/ml, and the other to receive intramuscular pethidine, 1 mg/kg. Preoperative and postoperative pulmonary function, postoperative pain scores, and days from operation to hospital discharge were recorded and statistically compared. There was no significant difference in pain scores, nor in days to discharge; however, postoperative pulmonary mechanics were significantly poorer in the interpleural group. A hypothesis to explain the differences is offered. PMID- 2596679 TI - Studies on Australian snake venoms. Part 1: The haemodynamic effects of brown snake (Pseudonaja) species in the dog. AB - The haemodynamic effects of Brown Snake (Pseudonaja) species (textilis, nuchalis, affinis) were investigated in anaesthetised, mechanically ventilated dogs. Blood pressure decreased to minimal levels five minutes after intravenous envenomation. Hypotension was accompanied by significant decrements in cardiac output and stroke volume and a rise in peripheral vascular resistance. Heart rate increased transiently during 0.5-2.0 minutes after envenomation but had declined below resting levels five minutes after envenomation. No statistically significant change was recorded in central venous pressure. Depression of myocardial contractility is postulated as the mechanism of venom induced hypotension. PMID- 2596680 TI - Comparison of the Finapres blood pressure monitor with intra-arterial manometry during induction of anaesthesia. AB - The Finapres (Ohmeda, Madison, U.S.A.) is a non-invasive device which continuously measures the arterial blood pressure in a finger and produces a real time display of the arterial pressure wave. It consists of a finger cuff with an infra-red transmission plethysmograph, a servo control box and a monitor unit. The device was compared with intra-arterial pressure monitoring in twenty patients during induction of anaesthesia for elective neurosurgical procedures. The differences between the two methods were considerable, ranging from -40 mmHg to +26 mmHg for mean pressure. While the Finapres has potential as a non-invasive continuous blood pressure monitor, the current model Finapres, as supplied, displays too great a variability for it to be used as an alternative to intra arterial pressure monitoring. PMID- 2596681 TI - A new comprehensive anaesthetic record. AB - Eternal vigilance and strict attention to detail are the 'sine qua non' of safe anaesthesia with the contemporaneous anaesthetic record being the documentation. As an alternative to the manifold and often inadequate forms currently in use, a new rapidly completed anaesthetic record incorporating a comprehensive checklist is presented. Guidelines of the Faculty of Anaesthetists, Royal Australasian College of Surgeons are met. It is argued that the chart improves safety not only by its direction to attention during the peroperative visit and equipment check, but also by its demand for the ongoing attention of the anaesthetist. Reservations are expressed about 'black box' recording by trend printout and a perspective for computerised and automated anaesthetic records is also discussed. PMID- 2596682 TI - Acid aspiration prophylaxis in Australian obstetric hospitals--a survey. AB - During 1987 a confidential survey of all hospitals in Australia providing obstetric services was undertaken to determine the antacid medications used routinely as prophylaxis against acid aspiration pneumonitis. Of the 567 hospitals surveyed, 379 (67%) responded. Of these, 243 hospitals provide an obstetric service which includes caesarean section, and 67% of these perform less than 500 deliveries per annum. Aspiration prophylaxis during labour was used in 22.4% of responding hospitals. Prior to elective caesarean section, 11.5% used no prophylaxis, and 39.4% used particulate antacids such as magnesium trisilicate mixture (33.3%) or Mylanta (6.1%). Sodium citrate mixture was the most popular therapy (37%). Results were similar in the emergency caesarean section group. The use of cimetidine or ranitidine was uncommon in all groups. Results of this survey suggest marked differences in attitudes towards acid aspiration prophylaxis between Australian and British obstetric anaesthetic practices. PMID- 2596683 TI - A method for implementing programmed infusion of thiopentone and methohexitone with a simple infusion pump. AB - We have tabulated the series of steps in infusion rate required to maintain constant arterial levels of thiopentone and methohexitone. The tables are based on multiexponential equations for infusion rate, derived from plasma drug efflux studies. In each table an initial bolus is followed by nine steps in infusion rate over three hours. The tables provide rates suitable for delivery by a standard syringe pump to achieve and maintain an arterial concentration of 10 mg/l of thiopentone and 5 mg/l of methohexitone. Other desired drug concentrations can be derived from the table by simple multiplication. PMID- 2596684 TI - How much dantrolene? A case of fulminant malignant hyperthermia. PMID- 2596685 TI - Preparation of theatres for malignant hyperpyrexia patients. PMID- 2596686 TI - Subcutaneous morphine. PMID- 2596688 TI - Oxygen supply pressure should be the highest. PMID- 2596687 TI - Complications and inappropriate use of minitracheostomy. PMID- 2596689 TI - A hazardous sigh. PMID- 2596690 TI - Thyroid pressure. PMID- 2596691 TI - Acute tonsillar airway obstruction after adenoidectomy. PMID- 2596692 TI - Anaphylaxis to thiopentone--a reply. PMID- 2596693 TI - Retrievals from Albury/Wodonga. PMID- 2596694 TI - Dangerous ampoule. PMID- 2596695 TI - Ethical guidelines to publication of chemical research. PMID- 2596696 TI - High-sensitivity peptide mapping by capillary zone electrophoresis and microcolumn liquid chromatography, using immobilized trypsin for protein digestion. AB - Procedures for the reduced-scale analysis of proteins by peptide mapping have been developed, allowing peptide maps to be obtained from picomole to femtomole quantities of protein. The use of trypsin immobilized on agarose gel and placed in a small reactor column has made it possible to reproducibility digest as little as 50 ng of protein. This represents a decrease in sample size of approximately 3 orders of magnitude from conventional tryptic digestion schemes. Separations of tryptic digests were accomplished by using either microcolumn high performance liquid chromatography (HPLC) or capillary zone electrophoresis (CZE). Separations of 100 ng (4 pmol) of tryptic digest samples of beta-casein were achieved with microcolumn HPLC, while separations of approximately 2 ng (80 fmol) of beta-casein tryptic digest (from a total sample size of 50 ng) were possible with CZE. Peptide maps from phosphorylated and dephosphorylated forms of beta casein were readily distinguishable using both separation methods, demonstrating an ability to detect a single amino acid modification in a protein. Relative standard deviations of peak retention or migration times were less than 3% for microcolumn HPLC and less than 1% for CZE. PMID- 2596697 TI - Determination of selenium in human blood by high-performance liquid chromatography with fluorescence detection. AB - Selenium was determined in human whole blood or red cells by high-performance liquid chromatography (HPLC) using a new internal standard. The method provides a 0.15-ng detection limit, a between-day standard deviation of 1% at the 20-ng level, and a 3% within-day standard deviation at the 1-ng level. Samples were wet ashed, and a selenium-diaminonaphthalene derivative was formed, followed by addition of tetraphenylnaphthacene internal standard, reverse-phase HPLC separation (10 min/run), and fluorescence detection. The detection limit was reduced by discrimination of fluorescence excitation of the selenium complex from the background using long-wavelength excitation (480 nm), removal of stray light in the excitation beam, and other optimizations described. Representative aliquots of frozen and thawed whole blood samples were obtained by using a nitric acid predigestion at ambient temperature. Procedures to validate the method included standard addition and neutron activation analysis. PMID- 2596698 TI - Laser fluorometric detection of porphyrin methyl esters for high-performance thin layer chromatography. AB - A new detection method is presented for the determination of porphyrins present in biological materials. Separation is accomplished by high-performance thin layer chromatography after esterification of individual carboxylic acid porphyrins. Detection is achieved by utilizing one of the visible lines of an argon-ion laser for fluorometric excitation. Good selectivity and detectability are demonstrated for the determination of porphyrin profiles in human urine. The detection limits for uro-, heptacarboxy-, hexacarboxy-, pentacarboxy-, copro-, and mesoporphyrin methyl esters are in the 18-35 pg range. PMID- 2596699 TI - Room-temperature phosphorescence of polynuclear aromatic hydrocarbons on matrix modified solid substrates. PMID- 2596700 TI - High-performance liquid chromatographic method for the determination of 9-(4 hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL-39123) in human plasma and urine. AB - A rapid, sensitive and reliable reversed-phase high-performance liquid chromatographic (HPLC) method with UV detection has been developed for the assay of a novel anti-herpes agent, 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123), in human plasma and urine. The drug and the internal standard, the structural analogue BRL-42377, were extracted from the biological matrix by adsorption on a cation-exchange column and were subsequently eluted under alkaline conditions prior to HPLC. The method is reproducible, with coefficients of variation of ca. 5%, and linear from 0.1 to at least 30 micrograms ml-1 in plasma and from 50 to at least 2000 micrograms ml-1 in urine. The method has been used extensively to measure BRL-39123 in plasma and urine samples generated during clinical studies and is adequate for defining pharmacokinetics at projected therapeutic doses. PMID- 2596701 TI - Multiple labelling of immunoglobulin G, albumin and testosterone with a fluorescent terbium chelate for fluorescence immunoassays. AB - Human immunoglobulin G, human serum albumin and testosterone were labelled with the 4-aminosalicylic acid derivative of diethylenetriaminepentaacetic acid complexed with terbium ions. An exceptionally large amount of label, of the order of a few hundred moles of complex per mole of analyte, could be conjugated to the compounds tested by the use of poly-L-lysine. Self-quenching appears to be minimal, even with this high local concentration of fluorophores. The tracers were stable at 4 degrees C, and gave competitive calibration graphs at physiological concentrations. PMID- 2596702 TI - Development of smooth muscle: ultrastructural study of the chick embryo gizzard. AB - The growth and differentiation of smooth muscle in the chicken gizzard were studied by electron microscopy from the 10th day in ovo to 6 months after hatching; during this period the organ grows 1000-fold in weight. At the earliest stage studied, smooth muscle cells, interstitial cells, and fibroblasts are immature but can already be clearly distinguished. The structural components of muscle cells develop in a characteristic sequence. Mitochondria are more abundant in immature muscle cells (8% in 14 days embryos and 7% in 19 days embryos) than in the adult (5%). Caveolae are virtually absent in the 11 day embryo; they become more common at the end of embryonic life, but continue to increase in relative frequency after hatching. Gap junctions appear around the 16th day in ovo as minute aggregates of connexons, which then grow in size, probably by addition of new connexons. In the earliest stages studied, myofilaments occupy 25% of the cell profile and are assembled into bundles accompanied by dense bodies and surrounded by loosely arranged intermediate filaments. By contrast, membrane-bound dense bands are scarce until the latter part of embryonic life, an observation suggesting that myofilament formation and alignment is not a process initiated near the cell membrane or directed by the cell membrane, and that only late in development bundles of myofilaments become extensively anchored to dense bands over the entire cell surface: at that time myofilaments occupy more than 75% of the cell volume. The muscle cells increase about four-fold in volume over the period studied; the 1000-fold increase in muscle volume is mainly accounted for by an increase in muscle cell number. Mitoses are found in the gizzard musculature at all embryonic ages with a peak at 17-19 days; they occur in muscle cells with a high degree of differentiation. These cells divide at a stage when they are packed with myofilaments and form junctions with neighbouring cells: the mitotic process affects the middle portion of the cell, which takes up an ovoid shape and eventually divides, whereas the remaining portions of the cell do not differ in appearance from the surrounding muscle cells. At all stages of development the population of muscle cells has a uniform appearance (apart from the cells in mitosis), and the growth and differentiation seem to proceed at the same pace in all the cells. There are no undifferentiated cells left behind in the tissue for later development. PMID- 2596703 TI - Monodelphis domestica (grey short-tailed opossum): an accessible model for studies of early neocortical development. AB - The development of the neocortex of the marsupial Monodelphis domestica has been studied from birth until adulthood. Monodelphis is born after a gestational period of 14 days, a time when the neocortex is still at a two-layered "embryonic" stage of development, that is equivalent to a 13-14 day rat embryo or 6 week human embryo. The cortical plate does not begin to appear until 3 to 5 days postnatal. Thus the whole of neocortical development is a postnatal phenomenon in this species, as has been previously described in other marsupials. The general pattern of development of the characteristic layers of the immature neocortex and the subsequent development of a six-layered adult neocortex is similar to that found in eutherian species. However there are some differences. The depth of the immature cortical plate when compared to the thickness of the neocortical wall is less than in eutherians and the subplate zone is much deeper in Monodelphis; this transient subplate zone consists of widely spaced rows of cells that are aligned parallel to the cortical surface. Unlike eutherians there appears to be no secondary proliferative zone in the subventricular zone of the dorso-lateral neocortical wall. Maturation of the neocortex is apparent by 45 days postnatal and by 60 days (around the time of weaning) the characteristic six layered adult neocortex is clearly present. The neuronal marker PGP 9.5 was used to define neuronal populations in the adult brain. The density of neurons in Monodelphis appears to be considerably less than in eutherians such as the rat. The suitability of postnatal Monodelphis for studies of neocortical development is discussed. PMID- 2596704 TI - Diffusion barrier properties of the perineurium: an in vivo ionic lanthanum tracer study. AB - While the perineurium as a diffusion barrier has been extensively investigated by light and electron microscopy, such studies have been largely restricted to the use of protein tracers. In the present study the permeability of the perineurium to a physiologically more relevant ionic tracer has been assessed. In vivo the rat sural or tibial nerve was either microinjected with lanthanum nitrate solution for endoneurial application or bathed in the lanthanum solution for epineurial application. The findings generally demonstrated an effective barrier to the tracer which failed to penetrate the inner layers of the perineurium. Only at the highest lanthanum concentration and longest time intervals employed did trace quantities occasionally penetrate the barrier and then only in the presence of some cytopathological changes to the outermost perineurial cells. The usefulness of the microinjection method was limited by the slight but unavoidable trauma to the perineurium. The findings are related to those of other studies which have used electron dense tracers, also to studies using physiological including electrophysiological techniques and morphological including freeze fracture methods. PMID- 2596705 TI - Synaptogenesis in the dorsal lateral geniculate nucleus of the rat. AB - Synapse formation and maturation were examined in the rat dorsal lateral geniculate nucleus (dLGN) from birth to adulthood. Examination of animals, whose ages were closely spaced in time, showed that the maturation of the synaptic organization of the nucleus takes place chiefly during the first 3 weeks of postnatal life. This period of maturation may be divided into 3 broad stages. During the first stage, which spans the first 4 days of life, there are only a few immature synapses scattered throughout the nucleus; occasionally aggregates of 3 or 4 synapses are encountered. Dendrodendritic synapses first appear at the end of this stage. The second stage, which lasts from the end of the first stage through day 8, is characterized by intensive synaptogenesis as well as extensive growth and degeneration. For the first time, large boutons resembling retinal terminals form multiple synaptic contacts with dendrites and dendritic protrusions; these synaptic arrangements are partially covered by glial processes. A feature characteristic of the developing dLGN during the first 2 postnatal weeks, and particularly during the second stage, is the presence of membrane specializations that resemble vacant postsynaptic densities. These specializations, which may be unapposed or opposite another neuronal process, decrease in frequency as the number of synapses increases. It is not known whether these densities are converted to synapses or whether they result from loss of presynaptic elements. The third stage in the process of synaptogenesis, which spans a period between days 10 and 20, is characterized by myelination and by the diminution of growth cones, degenerating profiles and vacant postsynaptic densities. There is also a very significant increase in the number and maturation of synapses including synaptic glomeruli. However, it is not until the end of this stage that synapses appear qualitatively indistinguishable from synaptic arrangements identified in adult animals. PMID- 2596706 TI - A study on skeletal myogenic cell movement in the developing avian limb bud. AB - Quail limb mesenchyme containing myogenic cells of somitic origin were transplanted into chick limb buds to determine whether cell movement might play a role in avian limb myogenesis. In general, cell displacement was not detected 1 day after implantation: all quail cells were found at the graft site. Migration was evident 2-days after implantation but not all cell types were capable of movement; myogenic cells were very invasive while chondrocytes were relatively immobile. The spreading of myogenic cells was discernible up to 4-days after implantation and specifically in a proximodistal direction towards the apex of the limb. PMID- 2596707 TI - Mitosis and cell death in the tail of the chick embryo. AB - Although somites develop from the mesoderm in the tail of the chick embryo, they do not form to the tip of the tail. Previous work has shown that this terminal mesoderm possesses many of the characteristics of the segmental plate mesoderm which gives rise to the somites in the trunk. This investigation is aimed therefore at understanding why the terminal mesoderm fails to form somites. Mitotic and pyknotic rates have been obtained for the tail region of chick embryos between stages 13 and 27. Embryos were treated with colchicine, so that the mitoses were blocked in metaphase, and counts were made on serial sections. The overall mitotic rates were highest between stages 15 and 18. Regions of high mitotic rate, which are an indication of cell synchrony, were found in the tail bud mesoderm though not in a consistent location, and only infrequently near the anterior end of the tail segmental plate. In the trunk however (Stern and Bellairs 1984) a single peak of cell synchrony was routinely found near the cranial end of the segmental plate. It is concluded that the cells of the tail mesoderm are less synchronised in preparation for somitogenesis than are the corresponding mesoderm cells in the trunk. A further conclusion is that the tail bud is not per se a region of high proliferation, though there are patches of high mitotic rate. The overall pyknotic rate reached a maximum at stage 25; peaks of pyknosis corresponded initially with the mitotic peaks and were associated with the ventral ectodermal ridge and the tail gut. By stage 25 however, the high levels of cell death were restricted mainly to the tip of the tail.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596708 TI - [Initial experience of work on a program of complete preservation of the patient's blood in heart surgery]. AB - A complex program on complete preservation of a patient's blood was adopted during and after cardiac surgery with extracorporeal circulation. The major principles of such a "hemotransfusionless" surgery are 1) to minimize irrevocable blood loss; 2) to fully return a cardioplegic solution into the blood during extracorporeal circulation; 3) to apply autohemotransfusion controlled by hemodilution and hemoconcentration; and 4) to reinfuse drained blood in the nearest postoperative period. One hundred and twelve patients were treated by the program. The average expenditure of donor blood per patient was 543 +/- 343 ml, donor blood was not transfused to 44 (39%) patients during their entire stay in hospital. PMID- 2596709 TI - [Liver circulation during acute cardiac insufficiency and the use of intra-aortic balloon counterpulsation]. AB - Liver hemodynamics was experimentally studied in a model of acute heart failure caused by successive ligation of coronary artery branches and the following cardiogenic shock and during assisted circulation using intraaortic balloon contrapulsation. It has been established that intraaortic balloon contrapulsation promotes to the elimination of hemodynamic liver disturbances, however no final recovery of the organ hemodynamics was observed after 2 hours of contrapulsation. The method of intraaortic balloon contrapulsation is recommended at early stages of acute heart failure prior to the onset of profound ischemic changes in the liver. PMID- 2596710 TI - [Neuroleptanalgesia, surgical trauma and immunity]. AB - Immune status and hormonal homeostasis have been studied in 26 patients with larynx cancer operated on (laryngectomy, extended laryngectomy) under neuroleptanalgesia. It has been established that 3 and 7 days after the operation there was a decrease in plasma cortisol level and an increase in B- and T lymphocyte count and theophylline-resistant T-lymphocyte count in the peripheral blood. In 4 patients with postoperative complications (pharyngeal fistulas) there was a reverse correlation between cortisol content and B-lymphocyte count and T lymphocyte blast transformation. PMID- 2596712 TI - [The efficacy of combined general anesthesia with electroacupuncture analgesia in abdominal surgery in patients with concurrent massive obesity]. AB - Combined anesthesia and electroacupuncture analgesia (EAA) were performed in 48 obese patients. Control group (50 patients) was subject to surgery under combined anesthesia with drugs for neuroleptanalgesia, calipsol and nitrous oxide. Stability of hemodynamics, glycemia level, esophagus and skin temperature gradient, minute diuresis during EAA, as well as absence of respiratory depression and postoperative adaptation mechanisms inhibition have been observed. EAA made it possible to do without narcotic analgesics and drugs for neuroleptanalgesia during surgery in obese patients and promoted early activation of patients in the postanesthesia period, normalization of lung ventilation and lower incidence of postoperative complications. PMID- 2596711 TI - [The effect of calypsol, thiopental sodium and fentanyl on the functional status of the sinoatrial node and the heart conduction system in patients with paroxysmal arrhythmias]. AB - 64 patients with paroxysmal arrhythmias caused in 44 cases by collateral atrioventricular pathways have been studied. Endocardial programmed electrical cardiostimulation was applied. It has been established that calypsol at a dose of 2 mg/kg significantly improves the functional state of the sinoatrial node, atrioventricular conduction and conduction in collateral atrioventricular pathways functioning both anterogradely and retrogradely. Fentanyl, already at a dose of 2.5 micrograms/kg inhibits considerably the functional state of the sinoatrial node, without affecting conduction in the normal AV system and in collateral atrioventricular pathways. Thiopental sodium at a dose of 7 mg/kg improves slightly the functional state of the sinoatrial node. PMID- 2596713 TI - [Provision of artificial ventilation of the lungs during endolaryngeal surgical interventions using a high-energy laser]. AB - To ensure controlled lung ventilation in endolaryngeal surgical interventions, using a high-energy laser, use was made of normal frequency jet ventilation (NFJV) and high frequency jet ventilation (HFJV) through a non-inflammable fluoroplast catheter supplied at a distal end with a device fixing it in a central position. HFJV seems preferable, as endolaryngeal manipulations become more convenient. The study was performed in 118 patients. Venturi effect was observed only during ventilation through a tracheostomic canule. It has been established that, unlike NFJV, in HFJV gas exchange parameters are much better, though oxygenation in NFJV is satisfactory in all the patients. PMID- 2596714 TI - [Intensive therapy using antioxidants in patients with lung cancer and respiratory insufficiency]. AB - Positive changes of respiratory function parameters and oxidation-reduction processes observed in 55 patients with lung cancer and low functional respiratory reserve indicate the advisability of introducing antioxidants and antiaggregants (cytochrome C, aevitum, Trental, rheopolyglucin) into complex intensive preoperative correcting therapy for the expansion of indications for surgery and attenuation of the operative risk. PMID- 2596715 TI - [Initial clinical experience with the use of an auxiliary liver device]. AB - The authors developed an artificial liver apparatus that comprised 2 running classifiers of blood or one running classifier and mass exchanger. The functionally active link of the apparatus is a suspension of living isolated xenohepatocytes obtained from the liver of pigs weighing 18-20 kg by a combined enzymatic and mechanical procedure. More than 100 in vivo laboratory experiments and 30 operations were performed in 20 patients with acute and chronic hepatic failure. Three patients died, the remaining showed significantly better biochemical parameters of blood and full recovery or stable remission. PMID- 2596716 TI - [The course of the early postoperative period in heart surgery patients in relation to the state of humoral regulatory mechanisms]. AB - It has been shown that the course and outcome of the early postoperative period in cardiosurgical patients are to a great extent related to the functioning of the adaptation systems under study and their interrelations. An essential role of sympathoadrenal system (SAS) in the control over hormonal body status has been established. It ensures, provided its activity is retained, interaction of other hormonal systems as a uniform functional mechanism in postoperative stress. Decreased activity and intrasystemic coordination of SAS combined with low activity of renin-angiotensin-aldosterone system and excessively activated hypophyseal-adrenal system in patients with postoperative complications are indicative of adaptation mechanism damage and are of negative prognostic value. PMID- 2596717 TI - [Echocardiographic evaluation of hemodynamics and myocardial function in children under 1 year of age following surgery under conditions of artificial blood circulation]. AB - Left and right ventricular myocardial contractility was assessed, using two dimensional echocardiography in the earliest postoperative period after cardiopulmonary bypass surgery in 60 children under 1 year of age. It has been shown that a hemodynamically smooth postoperative period is characterized by a 36 to 40% decrease in left ventricular ejection fraction depending on the type of heart valve defect and the variant of its correction. Such a decrease in contractility required a slight inotropic support in the first 24 hours after the operation; in this case cardiac index exceeded 2.5 l.min-1.m-2 already in the first postoperative hours. By day 15 after the operation cardiac index and ventricular contractility are fully normalized, but for cases when correction is of hemodynamic and not of anatomic nature or is accompanied by myocardial injury. PMID- 2596718 TI - [Clinical use of tramal in patients in the early postoperative period]. AB - Tramal was given to 204 patients who were operated on the lung, heart, abdomen. During pain therapy, good and satisfactory results were on average obtained in 75% patients operated on the lung, in 77%, on the heart, in 89%, on the abdomen, in 70%, on the great vessels. The absence of the inhibitory effect of the drug on the respiratory center and its slightly marked sedative effect allow one to recommend the agent for application in the early period following the surgery when narcotic analgesics still retain their effect and a real risk of their overdosage exists. During prolonged artificial pulmonary ventilation in the early postoperative period and in impaired adaptation of the patients to a respirator, tramal aids normalization of lung mechanics and hemodynamic parameters without eliminating and suppressing the patients' consciousness and results in cessation of muscular shivering. Adverse effects of tramal are of no decisive clinical significance and occur mainly when the drug is rapidly injected into the vein. PMID- 2596719 TI - [Biochemical and morphological aspects of the aggregation capability of thrombocytes in peritonitis]. AB - 44 patients with peritonitis of different etiology and two groups of differently aged donors (19 persons) have been examined. Blood plasma levels of malonic dialdehyde and platelet morphological properties have been studied. In patients with peritonitis platelets are deformed and solid platelet aggregates are observed. Platelet activation is accompanied by augmented malonic dialdehyde blood content, its level further increasing with the progress of peritonitis. PMID- 2596721 TI - [Morphological analysis of the rat cerebral cortex and hippocampus in the early postresuscitation period following arrest of the systemic blood circulation]. AB - Light optic and electron microscopic techniques were used to examine the brain of rats with visible neurological status recovered at day 4 following a 10-minute systemic circulatory arrest caused by compression of a vascular fascicle. Compensatory and recovering processes were shown to be the major processes in the brain at this time of a postresuscitative period. The highest magnitude of these processes was observed in the frontal and occipital cortex, the lowest was found in the hippocampal section CA3-5. Slight destructive changes in the cells were identified only at the ultrastructural level. The findings may aid to find measures that stimulate reparative processes in the central nervous system after a history of hypoxia. PMID- 2596720 TI - [The effect of bronchofibroscopy on the mechanics of breathing during disorders of bronchial patency in the postoperative period]. AB - Changes in lung ventilation and pulmonary mechanics have been studied after bronchoscopy (BS) performed in 22 patients with early postoperative bronchial patency disturbances. All in all the results of 27 BS procedures have been assessed. It has been found that according to the nature of respiratory changes the patients could be divided into 2 groups. In one group pulmonary mechanics improved right after the procedure. While in the other group BS was associated with an increase in aerodynamic bronchial resistance to inhalation, respiratory work and energy waste. The parameters returned to normal values within an hour. It was noticed that the second type of the reaction was characteristic of patients over 50 with low respiratory reserve, heart failure and hypoxemia. In such patients BS is recommended together with high frequency jet ventilation through a nasotracheal catheter. PMID- 2596722 TI - [The effect of the functional status of the CNS in the postresuscitation period on restoration of the neurologic status in dogs following systemic circulatory arrest]. AB - The use of caffeine or diazepam in experiments on dogs recovered after a 12-min circulatory arrest has no significant effect on the end points of resuscitation, as compared to the control. Diazepam has a more favourable effect on the recovery of central nervous system functions than caffeine. Combined use of caffeine and diazepam or lidocaine at certain stages of the early postresuscitation period accelerates the recovery of the neurological status and improves the outcome of resuscitation. PMID- 2596723 TI - [Evaluation of the function of the myocardium by carrying out anti- and orthostatic tests in patients in resuscitation units]. AB - Ortho- and antiorthostatic tests (OT, AOT) were performed in critically ill patients to assess cardiovascular system function. Two types of reactions were observed depending on changes in the cardiac index occurring in response to maximum load (transition from the supine -15 degrees into the upright position +15 degrees). In group 1 (58 tests) transition into the upright position caused a decrease in the parameters of the cardiac pump function, while in group 2 (43 (tests) an increase was observed. The results obtained indicate that these tests increase considerably the diagnostic value of central hemodynamic indexes in the assessment of the circulatory function and functional myocardial reserve in critically ill patients. PMID- 2596724 TI - [The effect of concurrent atherosclerosis on the permeability of the dura mater and the efficacy of epidural analgesia with morphine and dicain]. AB - The permeability of spinal dura mater (SDM) was examined for morphine and tetracaine hydrochloride in 7 suddenly died patients with profound morphological manifestations. Atherosclerosis was found to show an average 37% increase in SDM permeability. With this, the efficiency of postoperative epidural analgesia (EA) with morphine was studied in 32 surgical patients with concurrent atherosclerosis. EA was demonstrated to be not only beneficial for this category of patients, unlike control patients, but followed by a significant decrease in respiratory center sensitivity to CO2. It was concluded that the regularities found should be taken into account during EA with narcotic analgesics in patients with concurrent atherosclerosis. PMID- 2596726 TI - [Evaluation of ketamine-sombrevin general anesthesia during bronchoscopy in children]. AB - An analysis was made of 82 ketamine-sombrevin, 146 ketamine and 29 sombrevin general anesthesias performed during bronchoscopy in 257 children aged 3 to 15 years with primary tuberculosis and chronic nonspecific diseases of the lung. A procedure of ketamine-sombrevin anesthesia was described. Its adequacy was evaluated by comparison of cardiac intervalograms taken before and after tracheal intubation. There was an absence of vomiting and hallucinations when the agents were concomitantly used. It was concluded that this method might be used during bronchoscopy in children. PMID- 2596725 TI - [Methodologic aspects of isolated ultrafiltration of the blood in nonspecialized units]. AB - 14 isolated ultrafiltration procedures have been performed in 7 patients, using AT-196 device and renal dialyzer DIP-02-02. Volumetric blood flow was 100-120 ml/min; 1.0-1.2 l of ultrafiltrate were removed during 1 h. The patients' conditions gradually improved in the course of ultrafiltration procedure. A simple method of isolated ultrafiltration that can be used in any medical institution is described. PMID- 2596727 TI - [A case of successful resuscitation of an infant]. PMID- 2596728 TI - [Capillaria (Nematoda, Trichuridae) of wild swine (Sus scrofa) in Austria]. AB - Capillaria (Nematoda, Trichuridae) of wild boar in Austria. In a research on Capillaria species with wild boar in Austria 2 species could be found, C. spec. in the stomach and C. garfiai in the tongue. The morphological characteristics of both species were described and represented C. spec. could only be detected in one of 105 stomachs and intestines. C. garfiai, however, could be proved in 77 (= 69%) of 112 examined tongues. C. garfiai which parasitizes in the tongue epithelium causes pathological changes only to a slight degree, so that it is of almost no pathogenic significance. The frequency of infestation with eggs of Capillaria (with a high probability of C. garfiai) was 14.4% of 319 examined samples of faeces. The validity of C. spec. is discussed. Both species were detected at wild boar in Austria for the first time. PMID- 2596729 TI - Hospital stay and mortality attributed to nosocomial enterococcal bacteremia: a controlled study. AB - A retrospective cohort study of 97 patients identified by prospective hospital wide surveillance was conducted to determine the length of hospital stay and mortality attributed to hospital-acquired enterococcal bacteremia. The mean duration of hospitalization for cases was 83 days compared with 44 days for matched controls (p = 0.0001). The mortality rate during the study period was 43% among cases and 12% in matched controls (p less than 0.001). Thus the mortality rate attributable to enterococcal bacteremia was 31% and the risk ratio was 4.75. Stepwise discriminant function analysis indicated that the use of vascular catheters and renal dialysis and the presence of immune deficiency were predictors of fatal outcome in cases. Enterococcal bacteremia has become a prominent nosocomial pathogen and is associated with mortality rates well above those expected from the underlying disease. PMID- 2596730 TI - Handwashing practices in an intensive care unit: the effects of an educational program and its relationship to infection rates. AB - Handwashing is the single most important procedure in the prevention of nosocomial infections and yet it remains the most violated of all infection control procedures. With a sequential intervention study in an intensive care unit we have demonstrated that poor handwashing practices are associated with a high nosocomial infection rate, whereas good handwashing practices are associated with a low nosocomial infection rate. An educational and enforcement program designed to improve handwashing procedures can significantly reduce endemic nosocomial infection rates. PMID- 2596731 TI - Bacterial carriage by artificial versus natural nails. AB - Although health care workers are following fashion trends when they wear artificial nails, the implications of these nails for infection control is unknown. Cultures were obtained before and after handwashing from the fingertips of 56 nurses with artificial nails and 56 nurses with natural nails. After handwashing there were higher numbers of colony-forming units of gram-negative rods cultured from the fingertips of nurses with artificial nails than from nurses with natural nails. There were no significant differences in carriage of gram-positive cocci or normal flora. Because of the number of nosocomial infections caused by gram-negative rods, health care workers who wear artificial nails should consider the potential risk of increased carriage of gram-negative rods. PMID- 2596732 TI - Q fever in animal laboratory workers: an outbreak and its investigation. PMID- 2596733 TI - Follow-up and education of employees exposed to a patient with HIV antibodies and massive bleeding. PMID- 2596734 TI - The OSHA inspection process: one hospital's experience. PMID- 2596735 TI - Survival in patients with heart failure and normal basal systolic wall motion. AB - To assess the prognostic effect of preserved systolic function in patients with congestive heart failure (CHF), the authors analyzed survival curves in 91 nonselected adult patients with CHF. Patients were assigned to one of two groups on the basis of fractional shortening. The first group consisted of 44 patients with a normal fractional shortening (greater than 0.17), and the second group, of 47 patients with a fractional shortening of 0.17 or less. The two groups were similar in respect to all historical and physical findings. Median survival was eleven months for patients with a decreased fractional shortening and twenty-six months for patients with a normal fractional shortening. Patients with a decreased fractional shortening had a significantly shorter survival (p = 0.01). The authors conclude that congestive heart failure with preserved systolic function is common and is associated with a better prognosis, and the literature suggests it may require nonstandard therapy. Their data also suggest, however, that CHF patients with preserved systolic function cannot be reliably distinguished at the bedside. Rather, echocardiography or other tests of systolic wall motion are needed to make the diagnosis. PMID- 2596736 TI - Increase of walking capacity after acute aminophylline administration in intermittent claudication. AB - In the presence of peripheral atherosclerotic disease, inappropriate adenosine release during exercise might promote excessive arteriolar dilation leading to steal phenomena and ischemia. In order to test this hypothesis, IV aminophylline (6 mg/kg over fifteen minutes), a dosage known to effectively block adenosine receptors, was acutely administered--in a double-blind, placebo-controlled study design--in 13 patients with intermittent claudication and documented atherosclerotic disease. All patients performed two treadmill exercise tests at the same hour on two consecutive days, five minutes after aminophylline or placebo administration randomly allocated. Pain-free time was 109 +/- 133 (mean +/- SD) seconds after placebo and 173 +/- 165 seconds after aminophylline (p less than .01); maximum time to claudication was 273 +/- 191 seconds after placebo and 397 +/- 318 seconds after aminophylline (p less than .05). The authors conclude that intravenous aminophylline markedly increases the walking capacity in patients with intermittent claudication, possibly by preventing flow maldistribution phenomena through adenosine receptors blockade. PMID- 2596737 TI - Precordial ECG mapping in acute myocardial infarction (AMI) after intravenous infusion of streptokinase (s). AB - Repeated precordial ECG mapping (42 leads) and CK-MB serum measurements were done in 40 patients with anterior and/or anterolateral acute myocardial infarction. Twenty patients serving as controls, were treated with routine anticoagulant therapy. In 20 patients (the s group), randomly selected, a short-term IV infusion of 1,500,000 IU streptokinase was administered and followed by the same anticoagulant treatment as in controls. Ten subjects from each group underwent coronary arteriography one month later. From the analysis of ECG mapping the number of leads (N) and the sum of measurements (sigma) for each parameter were calculated. Before treatment there were no significant differences for all measured parameters between the two groups of patients. Seven days later, ST elevations were statistically different for NST and sigma ST with lower values for the s group. Higher values for NR and sigma R were also noted in this group. No statistically significant difference was found for NQ and sigma Q. CK-MB curve showed an earlier peak in the s group than in the control group. Five patients from the s group showed a patency of the infarct-related vessel. In conclusion, the results of this study show that patients receiving s have a significant benefit with ECG improvement. On the other hand, the CK-MB curve indicates an eventual recanalization to a certain degree in the obstructed coronary artery, which is the final goal. PMID- 2596738 TI - Early detection of silent ischemia after bypass grafting. AB - Silent ischemia (SI) is one of the predictable factors for crises after coronary artery bypass grafting. During the last six months 31 consecutive patients (range of age fifty-one to seventy-one years) underwent twenty-four-hour electrocardiographic monitoring (Holter) in the second postoperative week under ambulatory hospital conditions (total time 750 hours). The patients were investigated by two-channel ST segment Holter (CM1CM5). The results of the analysis were controlled by two independent observers. Criteria for SI were horizontal or downslope ST depression greater than or equal to 1 mm greater than or equal to 1 minute. Five patients (16%) underwent two to eight SI crises/twenty four hours (mean 4.3). PMID- 2596739 TI - Doppler assessment of the effects of isometric stress on left ventricular filling in hypertensive young adults. AB - Doppler interrogation at the in-flow of the left ventricle was used to test the effects of isometric stress on ventricular filling in 7 hypertensive subjects with mild to moderate left ventricular hypertrophy, aged forty-two +/- seven years, compared with 9 matched healthy control males. In the hypertensive patients at rest, peak early diastolic (E) velocity was lower, and atrial (A) velocity higher, with lower E/A peak velocity ratios than in normals (p less than 0.05). These differences were more accentuated during isometric stress. Atrial filling fractions were higher in hypertensives (37 +/- 6%) than in normals (24 +/ 7%) at rest, p less than 0.05, and this difference increased during isometric stress (44 +/- 9% versus 30 +/- 11%). Thus, isometric stress accentuated the reliance of left ventricular filling on atrial contribution and may be applied for the detection of early ventricular filling abnormalities in patients with mild hypertension. The systolic blood pressure and the hypertrophic process were both important determinants of left ventricular diastolic filling. PMID- 2596740 TI - Routine 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG) myocardial tomography using a normal large field of view gamma-camera. AB - There is a recent need to study glucose metabolism of the heart in ischemic, as well as in "hibernating or stunned" myocardium, and compare it with that in perfusion studies. In non-positron emission tomography centers, positron imaging is possible with a standard Anger-type camera if proper collimation and adequate shielding of the camera crystal can be achieved. For the study with fast-decaying isotopes, seven-pinhole tomography (7PHT), a limited-angle method designed for transaxial tomography of the left ventricle using a nonrotating camera, is well suited, because projections are acquired simultaneously. Individual adjustment (patient supine) of the camera's view axis (CAx) with the left ventricular axis (LVAx) gives excellent results: sensitivity for CHD 82%, specificity 72% in a prospective 201TI study (48 patients, x-ray coronarography as reference). Good alignment of CAx with LVAx is also achieved with the patient prone in LAO in a hammock above the camera surface. In this setting additional lead shielding of the camera is possible using a table reinforced with 5 cm of lead with a central hole for the 7PH-collimator, which has a special lead inlay. This allows utilization of the 511 KeV emitter 18F-FDG, which with a half-life of 109 minutes, can be transported a reasonable distance from the production site. System sensitivity and resolution for 18F was found comparable to 201Tl, 99mTc, and 123I using a phantom. First clinical examinations after 201Tl stress/redistribution studies showed increased 18F-FDG uptake in ischemic heart segments, as well as in "hibernating" nonperfused or "stunned" myocardium. PMID- 2596741 TI - Myocardial imaging using thallium 201 scintigraphy after dipyridamole infusion: a case history. AB - Coronary artery disease frequently occurs in combination with peripheral vascular disorders and is an important cause of morbidity and mortality during or after peripheral vascular surgery. However, the detection of coronary artery disease in patients with peripheral vascular disease may be complicated, since most of these patients are unable to perform conventional exercise testing. The authors report a sixty-two-year-old man with an infrarenally located aneurysm of the abdominal aorta who underwent thallium 201 scintigraphy combined with dipyridamole infusion as an alternative exercise test. The subsequent thallium 201 images showed perfusion defects indicative of severe coronary artery disease. Coronary angiography showed an occluded right coronary artery and a significant proximal stenosis in the left anterior descending coronary artery. The patient underwent successful aortocoronary bypass surgery, and two months later, the aortic aneurysm was operated on without complications. As a result, dipyridamole thallium 201 scintigraphy should be considered as a valuable diagnostic test to detect coronary artery disease in patients with peripheral vascular disorders. PMID- 2596742 TI - Hypotensive effects of nifedipine in patients with primary hyperparathyroidism: case reports. AB - Nifedipine was administered orally to 2 patients with primary hyperparathyroidism before and after parathyroidectomy. The operation lowered serum calcium concentration and parathyroid hormone but did not alter plasma renin activity, plasma aldosterone concentration, and serum magnesium. The hypotensive effects of nifedipine were markedly enhanced with the decrease in serum calcium concentration following parathyroidectomy. Thus, the level of serum calcium concentration may modulate the hypotensive effect of nifedipine in humans. PMID- 2596743 TI - Diastolic prolapse of a billowing mitral valve. PMID- 2596744 TI - The prevention of left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction. PMID- 2596745 TI - Silent mitral regurgitation in mitral valve prolapse. PMID- 2596746 TI - Treatment for clicking questioned. PMID- 2596747 TI - Maxillonasal dysplasia, mandibular retrognathia and cleft palate. AB - The present paper describes the craniofacial form of subjects with maxillonasal dysplasia and reports its occurrence in two siblings who also have cleft palate and mandibular retrognathia. Maxillonasal dysplasia and a cleft deformity may be illustrative of a field effect of a teratogen on developing midface components or even suggestive of a possible inherited etiology. PMID- 2596748 TI - Skeletal changes associated with extraoral appliance therapy: an evaluation of 200 consecutively treated cases. AB - Questions exist concerning the degree to which orthodontic treatment alters facial form. This study has attempted to discern changes in several measures of vertical facial form which might be influenced by varying vectors and amounts of extraoral force. The data were collected from pre- and posttreatment lateral cephalograms of 200 children treated consecutively with full edgewise orthodontic appliances. The sample was divided into three pretreatment groups based on the type of extraoral force delivered; cervical, "combi," and no-headgear. All groups showed a wide range of variation in treatment response, but did not demonstrate significant differences. While the extraoral forces predictably improved horizontal maxillo-mandibular discrepancies, there was too much variation in response to predict vertical changes. PMID- 2596749 TI - Incidence and etiology of midline diastema in a population in south India (Madras). AB - In a cross-sectional study of midline diastemas in a South Indian (Madras) population, 9,774 patients aged 13-35 years were screened. True midline diastema was defined as one without periodontal/periapical involvement and with the presence of all anterior teeth in the arch. Sample purification resulted in a research sample of 166 patients with true midline diastemas. The incidence of true maxillary midline diastema (160/9774-1.6%) was greater than that of true mandibular midline diastemas (31/9774-0.3%). No direct etiologic factor for the midline diastemas was noted. Spacing in the anterior region was the most significant factor associated with the midline diastema. PMID- 2596750 TI - The stability of anatomical and centroid reference points in cephalometric analysis. AB - Cephalometric records of 60 fetuses were combined on a coordinate reference grid to measure the statistical spread of the outlines. When centroid instead of anatomical points were used for superimposition of records, the spread of the outlines was reduced dramatically, being statistically significant (p less than 0.001). The centroid is a mean point being less variable and preferable to anatomical points commonly used for comparing successive cephalometric records. PMID- 2596751 TI - The effect of mandibular first premolar extraction on third molar space. AB - Change in molar space is compared in 48 mandibular first premolar extraction cases and 46 non-extraction cases over a five year period. Significantly greater increase in molar space is found in extraction cases. It is, to some extent, related to the initial degree of crowding. PMID- 2596752 TI - Case report CB. Surgical vs nonsurgical treatment in the nongrowing patient. AB - With an increase in the number of adults currently seeking orthodontic care, the orthodontist will invariably be faced with the planning and execution of treatment for nongrowing patients with significant skeletal discrepancies. Surgical orthodontic treatment may be the preferred mechanical choice in many of the cases, but may not fit the patient's financial or emotional capabilities. It is often incumbent upon the orthodontist to present alternative treatment options along with the risks and benefits inherent in the dentoalveolar compensation of a malocclusion which is predominantly skeletal. Traditional concerns have been with periodontal and dentoalveolar stability, intermaxillary dental function and soft tissue facial aesthetics with more recent focus on the medical-legal implications of potentially altered temporomandibular joint function. Ultimately the decision to undertake an alternative treatment plan, postpone combination surgical/orthodontic treatment or opt for no treatment must lie with the well informed patient. The following case represents many of the considerations and comprises involved with the treatment of a nongrowing skeletal Class II problem. PMID- 2596754 TI - New video on AIDS released from OSHA. PMID- 2596753 TI - 21st International Conference on Animal Blood Groups and Biochemical Polymorphisms. Turin, Italy, 4-8 July 1988. Abstracts. PMID- 2596755 TI - The diagnostic dilemma of milk allergy. PMID- 2596756 TI - Intermittent breathlessness. PMID- 2596757 TI - Diagnostic value of a lymphocyte stimulation test in cow milk protein intolerance. AB - In order to evaluate the diagnostic value of a lymphocyte stimulation test with casein and beta lactoglobulin in cow milk intolerance (CMI), we studied 26 patients with a diagnosis of CMI and 25 age-matched controls with intestinal diseases other than CMI. Lymphocyte stimulation test to casein (P less than .001) and beta lactoglobulin (P less than .001) was significantly higher among CMI patients. Seventeen patients were RAST positive and nine negative for whole milk proteins. No differences were found in the lymphocyte stimulation test response between RAST-positive and RAST-negative subjects. These results suggest that lymphocyte stimulation test with highly purified antigens in optimal concentrations is specific and could be useful in the diagnosis of CMI. PMID- 2596758 TI - Lack of effect of geographic elevation on mortality from asthma. AB - One might expect prevalence of asthma to affect rates of mortality due to asthma. In France, asthma prevalence at 1350 m is less than at sea level. Calculation of asthma mortality rates for blacks and whites 5 to 34 years of age in 1980 for counties in the USA with populated places at elevations of at least 4000 feet disclosed no significant differences from rates at lower elevations. Nevertheless, asthma mortality rates were significantly higher for blacks than whites at both high and low elevations. The asthma death rates per 100,000 general population for elevations less than 4000 feet were .160 for whites and .896 for blacks. Asthma death rates for elevations of at least 4000 feet were .209 for whites and 1.150 for blacks. PMID- 2596759 TI - Bahia grass pollen, a significant aeroallergen: evidence for the lack of clinical cross-reactivity with timothy grass pollen. AB - Thirty-eight subjects were challenged (25 nasal, 13 bronchial) with Bahia grass, Paspalum notatum, pollen extract. A positive Bahia intradermal skin test predicted a positive challenge to Bahia in all (11/11) of the nasal challenges and 75% (6/8) of the bronchial challenges. All 19 subjects with negative Bahia intradermal skin tests had negative challenges with Bahia. Specific IgE antibodies to Bahia pollen were detected by conventional RAST (greater than or equal to 2+) in 82% (14/17) of subjects with positive challenges and in 5% (1/20) of subjects with negative challenges. Eight subjects had positive intradermal skin tests to either Bahia (three) or timothy, Phleum pratense (five). Seven of the eight subjects reacted exclusively to either Bahia or timothy nasal challenge as predicted by their skin tests. Bahia grass is a significant aeroallergen, which in some subjects can be demonstrated not to cross-react with timothy. PMID- 2596760 TI - Immunopathology of nasal polyps: an immunohistochemical approach. AB - We studied the mast cells and the T-lymphocyte subpopulations of four patients' nasal polyps using immunohistochemical procedures. The data showed that MC displayed IL2-receptor and that they were very often closely related to CD4+ and MHC class II-positive T-lymphocytes. CD8-positive T-cells represented only 10% to 15% of the whole lymphoid population and were not localized near mast cells. These findings suggest a possible role of cell-mediated immune reactions in the pathogenesis of nasal polyps. PMID- 2596761 TI - Maternal immune status against beta-lactoglobulin and cow milk allergy in the infant. AB - Beta-lactoglobulin (BLG) is probably the major cow milk antigen. Serum levels of anti-BLG antibodies were determined prospectively in mothers. The results were analyzed according to the existence of allergic manifestations in infants during the first months of life. Mothers of babies who developed allergy had statistically lower IgG anti-BLG concentrations than mothers of infants who presented no symptoms (P less than .001). Together with IgE umbilical cord blood screening, determine maternal IgG anti-BLG concentrations can more clearly define the allergic risk in the infant. PMID- 2596762 TI - Specific IgE antibodies to 16 widespread mold genera in patients with suspected mold allergy. AB - A panel of 55 sera from patients with suspected mold allergy from two different geographic areas, A and B, was investigated for specific IgE antibodies to 16 individual molds using Phadebas RAST technique. The molds investigated were Alternaria, Cladosporium, Aspergillus, Penicillium, Mucor, and Candida from the former RAST panel and ten additional new mold genera. The RAST screening revealed that 73% of patients had specific IgE antibodies to at least one of the 16 molds. Eighteen percent were negative to the six molds of the previous RAST panel but had specific IgE antibodies to at least one of the ten new molds. The highest frequency of IgE antibodies in the A group could be assigned to Cladosporium, followed by Botrytis and Helminthosporium. In group B, sensitivity to Botrytis and Phoma showed the highest frequencies. This study revealed that the relative importance of mold genera may vary greatly between patient groups from different geographic areas. Some of the species of the expanded RAST panel seem to be at least as important as Alternaria and Cladosporium. Multiple sensitivities seem to be caused by sensitization by many mold species rather than by cross-reactivity. PMID- 2596764 TI - Adverse reactions to foods. PMID- 2596763 TI - Comparison of Alternaria tenuis extracts prepared from different raw materials. AB - Alternaria extracts, prepared from three different sources under the same conditions, were compared by several biochemical/immunochemical methods. Two raw materials (A,G) contained mostly mycelia. The third raw material (C) contained mycelia (35%) and spores (65%). Extracts A and G were different in total allergenic potency, antigen/allergen pattern, and in the Alt 1 content. Extract C was of similar total allergenic potency as extract A but showed a somewhat different antigen/allergen pattern and a different Alt 1 content. Although there were some compositional differences among the extracts, all extracts regardless of source materials (spores and mycelia) demonstrated strong RAST inhibition activity and parallelism of the inhibition curves. PMID- 2596765 TI - The expanding role of lymphoscintigraphy in the management of cutaneous melanoma. First Place Winner: Conrad Jobst award. AB - Accepted therapy for intermediate-thickness melanomas is wide local excision and regional lymphadenectomy for nodes known to be in the lymph drainage basin. Lymphoscintigraphy has been shown to be of great help in predicting the drainage pattern of truncal, shoulder, proximal extremity, and head and neck melanomas. Lymphoscintigraphy using Technetium-99 antimony sulfur colloid was performed on 17 patients with cutaneous melanomas at H. Lee Moffitt Cancer Center at the University of South Florida. Of 13 patients with primary truncal and shoulder lesions, drainage patterns were discordant 54 per cent of the time and resulted in dissection of nodal groups different than would otherwise have been planned. This resulted in several lymph nodes positive for metastatic disease removed from operative sites not expected to show metastatic spread by clinical experience alone. The discordant rate for head and neck drainage was also high with 2 of 3 forehead studies showing drainage to both anterior and posterior cervical chains when only anterior chain drainage was expected, while only one of these drained to the preauricular nodes. Again, this led to elective lymph-node dissections of nodal basins not anticipated on clinical grounds alone. After a mean follow-up of 2 years, in which 60 to 75 per cent of all recurrences from melanoma are expected to occur, there has been no lymph-node metastasis development in basins that were not predicted by the scan. It is clear from our data that well-known historical patterns of lymph drainage in addition to the clinical impression of experienced surgeons cannot reliably predict the lymphatic drainage of many truncal, shoulder, and head and neck melanomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596766 TI - Arterial injury complicating knee disruption. Third place winner: Conrad Jobst award. AB - Because dislocation of the knee (DK) is accompanied by a substantial risk of popliteal artery injury, the importance of arteriography in ruling out occult arterial damage in such patients is well accepted. However, because antecedent DK cannot be ruled out in a trauma victim presenting only with severe knee ligamentous disruption (LD), we have routinely performed arteriography in all patients presenting with grossly unstable knees, whether or not DK is present. To evaluate this policy we reviewed the records of 30 patients with either DK (n = 19) or severe LD (n = 11). There was no significant difference between DK and LD in the frequency of major (22% vs 18%) or minor (38% vs 36%) vascular abnormalities. We also found that Doppler pressure measurements were highly predictive of major arterial trauma in patients in whom it was used. We conclude that arterial injury should be ruled out in all trauma victims with severe knee ligament disruption, whether or not actual joint dislocation is present. PMID- 2596767 TI - Aneurysms of the hepatic arteries. AB - Seven patients with an aneurysm of the hepatic artery were investigated and operated on between 1976 and 1987. Five patients presented at the time of rupture and in three of those the aneurysm communicated with the biliary tree causing hemobilia. The aneurysm was located in the right hepatic artery in four patients; in the common hepatic artery in two patients, and in the left hepatic artery in one patient. Excision of the aneurysm was performed in five cases, but in two cases a liver resection had to be carried out. Five of the seven patients survived, including both patients who had elective surgery. It is concluded that hepatic artery aneurysms have a high tendency to rupture and therefore an elective operation should be performed in all patients with diagnosed aneurysm of the hepatic artery. PMID- 2596768 TI - Endoscopic management of gastric outlet obstruction following surgery for morbid obesity. AB - Surgery of morbid obesity is associated with significant morbidity, which is considerably increased for reoperative surgery. Over the past two and a half years endoscopic balloon dilation was performed in eight patients for stenosis of gastrojejunostomy following gastric bypass. The technique of dilation, indications, and pitfalls are discussed. The procedure was safe and effective. Patients who had dilation performed successfully avoided surgery entirely in seven of eight cases. Therapy was modified in two other patients based on endoscopy findings. Endoscopy was found to be more reliable and superior to upper gastrointestinal (UGI) series for evaluation of symptoms following gastric bypass procedures. Based on our experience and literature review we propose that endoscopy is the preferred alternative to major reoperative surgery and urge its wider use. PMID- 2596769 TI - Procedural skills of the general internist. A survey of 2500 physicians. AB - STUDY OBJECTIVE: To determine which of 40 clinical procedures general internists do in their practice, how often these procedures are done, and what training is needed to develop and maintain competence in each. DESIGN: Mailed survey. PARTICIPANTS: A random sample of 2500 American College of Physicians (ACP) members identified as general internists; 1806 (72%) responded. Of these, we excluded 398 who were board eligible or board certified in a subspecialty and 143 with unknown status. The resulting sample of 1179 was augmented in selected analyses by an additional sample of 199 rural internists. RESULTS: General internists did, on average, 16 of the 40 procedures. Practice characteristics markedly affected the number and variety of procedures done. A larger number of different procedures was independently associated with smaller cities, smaller hospitals, younger age, increased hours in patient care, and certain regions of the country. Practice characteristics varied considerably by practice type and location. Many procedures were done infrequently. There was reasonable agreement on the experience needed to attain and maintain competency in each procedure. The majority of respondents favored hospital credentialing for 22 of the 40 procedures. CONCLUSIONS: General internists do a wide variety of procedures, the number and frequency of which are affected by the characteristics and location of their practice. Despite opinion to the contrary, more recently trained general internists do a wider variety of procedures than older colleagues. These results provide data to help define standards for training and credentialing and suggest that we should reexamine general internists' training in procedural skills. PMID- 2596770 TI - Parental leave for residents. American College of Physicians. PMID- 2596771 TI - Reversible cardiomyopathy associated with cocaine intoxication. PMID- 2596773 TI - Resuscitation orders. PMID- 2596772 TI - Anaphylactoid reactions reported after treatment with ciprofloxacin. PMID- 2596774 TI - Cholesterol guidelines. PMID- 2596776 TI - Ovarian cancer, inflammation, and CA-125. PMID- 2596775 TI - Treatment for stroke. PMID- 2596777 TI - Busulphan and phenytoin. PMID- 2596778 TI - Variability of pulmonary function in alpha-1-antitrypsin deficiency: clinical correlates. AB - STUDY OBJECTIVE: To determine the range of pulmonary function variability in alpha-1-antitrypsin-deficient persons and to identify epidemiologic factors and pulmonary symptoms and conditions associated with this variability. DESIGN: Case series ascertained through investigation of extant obstructive lung disease (index cases, 22 subjects) or by other means (non-index cases, 30 subjects). SETTING: Referral-based pulmonary division at a tertiary care medical center. PARTICIPANTS: Fifty-two alpha-1-antitrypsin-deficient persons of type Pi Z ascertained by: extant chronic obstructive pulmonary disease (22 cases), family studies (20 cases), liver disease (4 cases), population screening (4 cases), and other pulmonary problems (2 cases). MEASUREMENTS AND MAIN RESULTS: Pulmonary function tests and a version of the American Thoracic Society 1978 standard respiratory epidemiology questionnaire were used. Persons of type Pi Z who were not specifically ascertained with chronic obstructive pulmonary disease had values of forced expiratory volume in 1 second over 65% of predicted in 20 out of 30 cases and frequently had normal lung function. Univariate and multivariate analyses of possible causes of lung disease showed that the following factors were significant (P less than 0.05): pulmonary symptoms (effects associated with chronic obstructive pulmonary disease), including dyspnea and chronic cough; age and pack-years of smoking (epidemiologic correlates); and other pulmonary conditions (potential causes or effects) including asthma, pneumonia, and episodes of increased cough and phlegm. Finally, we found a striking excess of questionnaire-reported parental emphysema in families of type Pi Z persons with chronic obstructive pulmonary disease compared with families of type Pi Z persons without disease. CONCLUSIONS: Many persons with alpha-1-antitrypsin deficiency do not have clinically significant lung function impairment: the perceived natural history of antitrypsin deficiency has been distorted by ascertainment bias. In addition to cigarette smoking, it appears that asthma, lower respiratory infections, and possibly some familial factors contribute to a severe clinical course. Follow-up of our cohort with widely varying lung function will provide insights into the natural history of the emphysema associated with alpha-1 antitrypsin deficiency. PMID- 2596779 TI - [Value of radiotherapy in bronchial neoplasms]. PMID- 2596780 TI - [Peroperative radiotherapy]. PMID- 2596781 TI - [Action of liposomal superoxide dismutase on measurable radiation-induced fibrosis]. AB - Radiation-induced fibroses are a classical complication of radiotherapy. We have studied the effect of liposomal superoxide dismutase (Lipsod) on 45 radiation induced fibroses of measurable volume and hardness in 34 patients. Over 3 weeks, 6 injections of Lipsod were given intramuscularly: 5 mg for 28 patients and 2 mg for 6 patients. On the average, the volume decreased by 32%. A marked or moderate softening was observed in 80% of the fibroses; it was accompanied by functional improvement in 75% of the patients (in cases of preexisting difficulties). The effectiveness was independent of the time lag between the Lipsod treatment and irradiation. The decreases noted in the volume and hardness of the fibroses remained stable during a follow-up of 5-24 months. This systematic study shows the interest of Lipsod treatment of quasi-experimental fibroses where no other effective therapy exists. PMID- 2596782 TI - [Diagnosis of bilateral secondary tumors of the kidney. Contribution of cytology. Apropos of 2 cases]. AB - The authors report bilateral secondary tumors of the kidney in two patients: one previously treated for an epidermoid tumor, the other for an anaplastic bronchial tumor. In both patients, clinical and radiological features were those of a malignant process. Scan-guided percutaneous fine needle aspiration provided the material necessary to make a definitive cytological diagnosis; it was thus possible to assess the malignancy and recognize the histological type of lesions. PMID- 2596783 TI - [Anatomo-clinical conference at the Pitie-Salpetriere Hospital. Abdominal pain and inflammatory syndrome]. PMID- 2596784 TI - [AIDS in elderly patients. Apropos of 22 cases observed in the Paris region]. AB - If geriatric AIDS is defined as the occurrence of this disease in individuals over 60 years old, it represents about 5% of the cases reported to the Direction Generale de la Sante by the end of 1988. We retrospectively analyzed 22 clinical cases of geriatric AIDS observed between 1985 and 1987, i.e. 21% of the cases reported at that time. In 55% of them, infection resulted from contaminated blood transfusions. Initially, hospitalization was indicated due to a significant deterioration of the patient's general condition, however, neuropsychiatric disorders and intellectual degeneration were present in 18% of the cases. Biological anomalies at the time of admission were classical with the exception of a high frequency of leukopenia often associated with anemia or thrombopenia. During the evolution of the disease, opportunistic infections were very common (90% of the cases). However, the major characteristic of this clinical form of AIDS is the high percentage (55%) of patients suffering from major neurological and psychiatric disorders, including subacute encephalitis in more than half of these patients. The prognosis is very bad, with an average survival time of 4.3 months from the time of diagnosis (median 2.5 months). The cumulative effect of the delay in diagnosing AIDS during the first hospitalization and the classical seriousness of encephalitis suffice to explain the very poor prognosis in patients whose age can play a role in altering the immune response. PMID- 2596785 TI - [Circulating anticoagulants in immunodeficiency virus infection. Results of a prospective study of 157 seropositive patients]. AB - One hundred and fifty-seven HIV seropositive patients were included in a prospective study of coagulation parameters. Activated partial thromboplastin time, prothrombin time, thrombin time and specific factor assays of the intrinsic pathway were performed using standard techniques. The tissue thromboplastin inhibition test and antiphospholipid antibodies were used to establish the presence of circulating lupus anticoagulant. Among the 46 patients with a prolonged activated partial thromboplastin time, an anti-prothrombinase was present in 33. Of the 111 patients with a normal activated partial thromboplastin time, anti-prothrombinase was present in 51. Circulating lupus anticoagulant seems to be common in HIV seropositive patients, since it was found in 84 patients (53.5%). Our findings confirm that the presence of circulating anticoagulants is not particularly associated with opportunistic infections or the development of the disease. It is possible that these inhibitors could be mediated by anti-phospholipid antibodies. In HIV seropositive patients, defective T cell regulation of B cells leads to polyclonal hypergammaglobulinemia. These antibodies may be directed against endogenous or exogenous phospholipids. PMID- 2596786 TI - [Diabetic papillopathy and bilateral ischemic anterior optic neuropathy]. PMID- 2596787 TI - [Adrenoleukodystrophy. Apropos of a case]. PMID- 2596788 TI - [Renal lithiasis, a logical complication of long-term treatment of glaucoma with a carbonic anhydrase inhibitor]. PMID- 2596789 TI - [Extramedullary pancreatic localization of myeloma]. PMID- 2596790 TI - [Relapsing polychondritis and cancer. 2 cases]. PMID- 2596791 TI - [The association of bronchial carcinoma and rheumatoid purpura]. PMID- 2596792 TI - [Pregnancy in Sheehan's syndrome. 4 pregnancies in 2 Nigerian women]. PMID- 2596793 TI - [Group G streptococcal infections. 3 patients with septicemia]. PMID- 2596794 TI - [Non-Hodgkin's malignant T-cell lymphoma in Gougerot-Sjogren syndrome]. PMID- 2596795 TI - [Procedural directions for a perinatal necropsy protocol usable for data bank purposes]. AB - The authors expose the problems to be solved preliminarily in order to obtain a perfect standardization of autoptic protocols concerning perinatal subjects. Therefore the propose a draft of detailed anamnestic clinical card that follows the woman and the conception product during and after the pregnancy, and suggest the ways for an adequate perinatal diagnostic autoptic protocol. They deem advisable to insert the anamnestic clinical summary, codified with the SNO-MED, in an autoptic data bank, an irreplaceable instrument of interdisciplinary study. PMID- 2596796 TI - [Perineometry and stress incontinence]. AB - The authors have examined 20 patients with genuine stress incontinence and urogenital prolapse and 20 control subjects searching a difference between static and dynamic condition of the pelvic floor. They used a simple device to study the mean position of the perineal plane both at rest and under switch. In incontinent patients the perineal plane is always below the bituberal plane (+1.17 cm at rest and +1.32 cm straining). These values are on a higher plane in the control subject (-0.64 cm at rest and +0.48 cm upon straining). These differences have an highly significant statistical value (P = 0.0002 and P = 0.001). PMID- 2596797 TI - [Comparison among perineometric, radiologic and electromyographic parameters in patients with urinary stress incontinence]. AB - In order to increase our knowledge of the physiopathology of urinary stress incontinence related to pelvic relaxation, the Authors examined 20 women suffering from SUI (Stress Urinary Incontinence) almost always characterized by concomitant slight or moderate urethrocystocele and 20 women without urological problems. They analyzed and compared the measurement of perineal descent with radiological and electromyographic parameters in order to detect if a suffering of some fibers of the pudendal plexus can be related to the pathology of SUI. They pointed out that patients affected by SUI show a perineal position, either at rest and under switch, below the ischial tuberosities plane. Furthermore the anterior angle at rest is always more than 30 degrees and electromyographic records are pathological in 90% of cases. PMID- 2596798 TI - [A further case of generalized muscular nevus with a "Michelin baby" clinical aspect associated with cutaneous mastocytosis]. PMID- 2596799 TI - [Psoriatic acro-osteolysis. Exclusive subungual pustular form associated with distant psoriasis vulgaris]. PMID- 2596800 TI - [Acquired hypertrichosis of the eyelashes in AIDS]. PMID- 2596801 TI - [Phenytoin and hirsutism]. PMID- 2596802 TI - [Halo nevus]. PMID- 2596803 TI - [Coexistence of pemphigus vulgaris, lichen planus of the mouth mucosa and hepatitis B]. PMID- 2596804 TI - [Biological diagnosis of infection caused by human immunodeficiency virus (HIV)]. PMID- 2596805 TI - [An immunohistochemical study on the effects of sulconazole on cellular response to dermatophytic skin infections]. PMID- 2596806 TI - [Epidemiological aspects of superficial mycoses]. PMID- 2596807 TI - [Nomenclature proposed for the species described in the subfamily of Ostertagiinae Lopez-Neyra, 1947]. AB - The species of the subfamily Ostertagiinae are reclassified according to the following characters: bursal ray pattern (2-1-2 or 2-2-1), relative length of ribs, and synlophe. Six genera are recognized: Marshallagia Orloff, 1933, Camelostrongylus Orloff, 1933, Ostertagia Ransom, 1907, Longistrogylus Le Roux, 1931, Spiculopteragia Orloff, 1933, and Teladorsagia Andreeva et Satubaldin, 1954. This paper does not intend to confirm or not the synonymies proposed by the authors. The paper also does not deal with problems of polymorphous species. Homonymies are indicated in chronological order and without creation of new names. PMID- 2596808 TI - [Population dynamics of Rhipicephalus pusillus Gil Collado, 1938 (Acarina, Ixodidae) in 1986-1987 in south-eastern Spain: modelling of the biological cycle]. AB - The evolution of the Rhipicephalus pusillus population, a parasite of the european wild rabbit, Oryctolagus cuniculus, is studied in a locality of the Province of Granada (Spain), in 1986-1987. The moving average technique was applied to the sampling data (358 hosts), for each stage of the postembryonic cycle. This technique permitted us, together with the habitual usage of the statistics, to understand in a more complete manner, the evolution of daily changes which affect the average number of ticks over the population of the host rabbits. Various factors allowed us to envisage a strong dependency of the parasitism of the females and the larvae in relation with the developing environmental conditions, which determine the apparition and concentration of the parasites on the hosts. A very strong correlation between the parasitism by male ticks and that of the female ticks was observed for the two year duration of our investigation. However, the moment at which the distribution of the ectoparasites is contagious, the male abundance is nearly twice that of the females. The larvae respond to a similar pattern of distribution both years, but it is necessary to note a delay, which we can attribute to climatic changes registered from one year to the next. The nymphs, on the other hand, present a different distribution curve for each year. Their presence depends on climatic conditions and especially that of the situation of the ticks and hosts population in the moments proceeding: these conditions determine a deplacement of their apparition in one sense or another. PMID- 2596809 TI - Blastocystosis in Italy. PMID- 2596810 TI - [Iopromide 300 and 370]. PMID- 2596811 TI - [Conventional cerebral arteriography. Study of a new non-ionic contrast medium: iopromide 300]. AB - Twenty-four patients were included in an open study of iopromide 300, a new non ionic contrast medium, to evaluate the feasibility of conventional arteriography of the brain. Iopromide 300 is a good candidate for this examination, on the basis of the safety and efficacy evaluated in this study. PMID- 2596812 TI - [Value of a new non-ionic contrast medium, iopromide 300 in renal arteriography using an arterial route. Comparative study with ioxaglate 320 mgI/ml]. AB - Thirty-nine patients with hypertension were included in a prospective randomized trial comparing two contrast media in intra arterial digital subtraction arteriography of renal arteries. Efficacy and safety were evaluated for a new non ionic contrast medium, iopromide 320 and the ionic low-osmolar medium, ioxaglate 320 mgI/ml. We have been able to show a statistically significant difference between these two products: iopromide 370 is, in this situation, less painful than ioxaglate 320 mgI/ml. PMID- 2596813 TI - [Renal tolerability of iopromide 370 in patients with chronic renal insufficiency]. AB - Intravenous injection of iodinated contrast media usually induces modifications of renal function. Adverse effects of contrast media on renal function may affect diuresis, blood flow or glomerular filtration rate. These modifications are mainly related to osmolality but also chemotoxicity. This open study showed that after i.v. injection of a bolus of iopromide 370, a new nonionic contrast medium, there was no untoward effect on renal function in patients with renal insufficiency. This justifies comparative studies in patients with renal impairment including elderly subjects, to confirm the tolerance of this product in high risk groups. PMID- 2596814 TI - [Laser angioplasty]. AB - Laser energy is capable of breaking up plaques of atheroma to clear obstructed arteries. Laser rays are transmitted by optic fibers, fine and flexible, or bundles of fibers. In order to avoid perforation of the arterial wall, major difficulty and pitfall of this technique, a centering balloon is used or an absorption gradient between plaque and normal tissue, or improved guiding devices such as angioscopy, ultrasounds or detection of the atheroma by spectroscopy. The laser energy may also be transformed into heat, procedure carried out by thermoplasty. In order to avoid the drawbacks of the cutting end of the bare optic fibers, it may be covered with sapphire optics which conducts well laser energy. Arterial and coronary disobstructions were performed by so called continuous lasers, such as Argon, YAG of pulsed laser such as Excimer or color lasers. These are selectively absorbed by the atheroma and operate according to a computerized system after detection of atheromatous plaques by spectroscopy. Excellent results have recently been obtained with such a system on short and long term complete peripheral arterial obstructions. PMID- 2596815 TI - [Application of auto-expansible endoprostheses to arteries of the legs]. AB - An endovascular support inserted percutaneously, may represent an attractive solution to prevent early obstructions and recurrent stenoses after angioplasty (ATP). 23 iliac lesions and 40 femoro-popliteal lesions, symptomatic in 55 patients, were treated with endoprostheses of the Wallstent type. For the iliac implantations, it concerned in one case a recurrence after endarterectomy, 13 cases of recurrent stenoses after ATP and 9 cases of immediate failure of the angioplasty. The mean length of the lesions under treatment was 8 cm (extreme values between 4 and 14 cm). For the femoro-opoliteal arteries, the implants concerned lesions ranging between 3 and 7 cm, in 75 p. cent of the cases, and lesions exceeding 7 cm in 25 p. cent of the cases. Three iliac thromboses and six femoro-popliteal thromboses were reported at the beginning of this study; on the contrary, no thrombosis is present in the last 18 patients treated with oral anticoagulants. The rate of recurrent stenosis is low (none at the iliac level and 10 p. cent at the femoro-popliteal level); in all other cases an excellent clinical result was obtained with a mean follow-up of 18 months. PMID- 2596816 TI - [The necessary advantage of measuring the pulsatile arterial flow of the limbs in patients with arterial disease]. AB - Proper determination of vascular haemodynamics requires measurement of flow and pressure. The objective of this study is to provide methods of measurement of the arterial flow, which may currently be performed via an external approach. The techniques in question include non-invasive electromagnetic flowmetry (NMF) and flowmetry by NMR. NMF uses external magnets, the signal is collected by common cutaneous electrodes; the equipment is simple and may be used in a cardio angeiology office. It main advantage lies in the screening of arterial diseases (very reproductable and sensitive), monitoring of the treatment (unrelated to the operator), study of hardened arteries (diabetes). Flowmetry by NMR requires a more sophisticated and costly equipment; it permits staged measurements, as well as a scan permitting measurements in one single artery; it is mostly used in specialized centres. Arterial lesions may be defined as not yet significant when only the blood pressure is considered, while the pulsatile flow is already altered; transluminal angioplasties performed in these circumstances, permit to restore the clinical picture as well as increasing twofold the initial flow. PMID- 2596817 TI - [Value of measuring transcutaneous oxygen pressure in arterial disease of the legs]. AB - The authors specify the methods used for measuring teh transcutaneous oxygen pressure (TcPO2), then present the four main advantages of the TcPO2. 1. Although the decision to amputate remains controlled by the clinical evaluation, TcPO2 is useful when one has to choose to preserve or not the heel support or the knee joint, when hesitating on the indication of amputation or the nature of the pain of a stump. Two measurements are crucial: a value of TcPO2 in a decubitus position greater than 30 mmHg at the amputation level seems to guarantee a primary healing, while under 10 mmHg, failure is the rule. 2. Correlations between the Fontaine classification and TcPO2 measured on the fore-foot in decubitus position, show that, at stages I and II, the TcPO2 is not significantly decreased in comparison with the control group (54 +/- 12 mmHg at stage I, 49 +/- 11 mmHg at stage II) and that at stages III and IV, TcPO2 is significantly much lower than at stages I and II and the value of 10 mmHg seems a remarkable threshold defining severe ischemias (12 +/- 15 mmHg at stage III, 3 +/- 5 mmHg at stage IV). 3. A prospective study of 66 arterial disease of the lower extremities cases, at stages II and IV, validated by a TcPO2 measured at the fore-foot in decubitus position less than 10 mmHg, and which could all benefit from reconstructive arterial surgery, is presented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596818 TI - [Role of myocardium scintigraphy with thallium dipyridamole in the evaluation of arterial disease of the legs]. AB - Thirty-eight consecutive patients with severe arterial disease of the lower extremities benefited from an exploration of the coronary reserve by myocardial scintigraphy with thallium dipyridamole. With this examination, it has been possible to screen 20 p. cent of asymptomatic patients and at least modify the perioperative treatment or even the very indication for surgery. PMID- 2596819 TI - [Education of patients with arterial disease. A plan for the use of Expert System in angiology via Minitel]. AB - We are presenting a computer program requiring the use of an Expert System accessible by Minitel, intended for patients with arterial disease and their attending physician. The objective is not to make a diagnosis, but to train the patients in applying health measures to the handling and prevention of his/her disease. While remaining anonymous, the patient may consult the program at home, without any time constraint. Only the patient's physician can authorize him/her to have access to the program. The Expert System may adjust the answers to the patients according to the past history and recent data. Contrary to a computer program, new knowledge does not impair the functioning of the system. The physician has access to simplified modules regarding his patient, and specific modules regarding the treatment. Such a system would help general practitioners in following his patient and would facilitate the Doctor-Patient relationship during consultations. PMID- 2596820 TI - [Cardiovascular deconditioning syndrome during space flight]. AB - Weightlessness results, in Man, in a redistribution of organic fluids from the lower half of the body to the thoraco-cephalic areas. This fluid transfer is responsible, in the course of the flight, for a series of subjective and objective disorders which the astronauts will experience. These disorders are related to venous stasis in the thoraco-cephalic area. Moreover, upon return of any space mission, regardless of its length, the astronauts will experience a disadaptation of their cardiovascular system indicated by hypotension with the possible occurrence of a presyncopal state, or even a syncope and a lowered stress capability. The haemodynamic consequences of this fluid transfer, from central and peripheral standpoint, and the mechanisms implicated in the cardiovascular deconditioning syndrome, are presented and discussed. PMID- 2596821 TI - [Vascular arterial effect of labetalol evaluated by measuring arterial distensibility during the exercise test]. PMID- 2596822 TI - [21st French Congress of Endocrinology. Strasbourg, 12-14 October 1989. Abstracts]. PMID- 2596823 TI - Assignment of the coding sequence for carcinoembryonic antigen (CEA) and normal cross-reacting antigen (NCA) to human chromosome 19q13. AB - We have isolated and localized to chromosome 19 a genomic sequence for carcinoembryonic antigen (CEA). A human cosmid bank was screened with two degenerate oligonucleotide sequences corresponding to N-terminal segments of the protein. Sequence analysis of a selected cosmid has confirmed the presence of an exon representing the 107 amino acids of the first protein domain (plus part of a putative leader sequence). In situ hybridization of both the exon DNA sequence and a more extensive genomic fragment to replication banded chromosomes has indicated that CEA and strongly cross-hybridizing members of the CEA family can be assigned to 19q13. This conclusion is supported by studies with a somatic cell hybrid cell-line. PMID- 2596824 TI - Localization of the Surfeit gene cluster containing the ribosomal protein gene L7a to chromosome bands 9q33-34. AB - The Surfeit gene cluster which contains at least four very tightly spaced unrelated genes, one of which encodes the ribosomal protein L7a, has been localized by an analysis of somatic cell hybrids to the long arm of chromosome 9. By the use of in situ hybridization the Surfeit locus has been further mapped to 9q33-34. PMID- 2596825 TI - Sequence of full length cDNA for human S-adenosylhomocysteine hydrolase. AB - Two cDNA clones for human S-adenosylhomocysteine hydrolase isolated from a placental cDNA library were sequenced. Each contained a sequence of 1299 nucleotides encoding a 432 amino-acid protein of MW 47,660. Clone 16-1 contained 47 nucleotides 5' of the coding region, and a 780 nucleotide 3' flanking region terminating in a poly A tail. In addition, a 101 nucleotide unprocessed intron interrupted the coding sequence at nucleotide 854 (second base of codon 285). Clone 20-1 contained 43 nucleotides 5' and 742 nucleotides 3' flanking the uninterrupted coding region. Besides the intron, the clones differed in one position of the coding sequence and at two positions of the 3' non-coding region. The cDNAs for human and rat S-adenosylhomocysteine hydrolase were identical at 91.5% of positions in the coding sequence and showed 70% homology in the 3' non coding regions. Human and rat S-adenosyl-homocysteine hydrolases are identical at 97% of amino-acid residues, and the Dictyostelium and human enzymes at 75%. PMID- 2596827 TI - Regional localization of the sperm-specific lactate dehydrogenase, LDHC, gene on human chromosome 11. AB - A cDNA clone complementary to the mRNA encoding the sperm-specific lactate dehydrogenase, LDHC, has been used to map the LDHC locus to the short arm of human chromosome 11. In situ hybridization data and analysis of mouse/human somatic cell hybrids carrying deletions of human chromosome 11 suggest that the gene is localized at p15.3-p15.5 close to the LDHA gene. PMID- 2596826 TI - Isolation of a cDNA clone and localization of the human glutathione S-transferase 3 genes to chromosome bands 11q13 and 12q13-14. AB - A partial cDNA clone of the glutathione S-transferase 3 gene (GST3) was obtained by screening a lambda gt11 human lung cDNA library with antiserum to human lung GST3. The sequence of this cDNA showed two base differences from the coding sequence of a GST3 cDNA isolated from a human placental cDNA library. Hybridization of the cloned GST3 cDNA to human chromosomes resulted in a primary peak of grains over band 11q13, a localization predicted by prior experiments. An unexpected strong secondary peak of grains was obtained over bands 12q13 and 12q14, indicating that there is a GST3-like gene on the long arm of chromosome 12 in man. PMID- 2596828 TI - Different polymorphic variants of glucose-6-phosphate dehydrogenase (G6PD) in Italy. AB - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in Italy and recent biochemical and kinetic studies have demonstrated the presence of polymorphic variants associated with severe or mild enzyme deficiency. We performed a biochemical characterization of G6PD in a large number of Italian G6PD deficient men in an attempt to identify the most reliable biochemical indices for discriminating polymorphic G6PD variants and to define their distribution throughout the country. Three polymorphic G6PD variants, respectively named Mediterranean, Cagliari and Sassari, were identified. The elution profile on DEAE Sephadex column chromatography, substrate analogue utilization and the Michaelis constant for G6P were the most significant parameters to discriminate polymorphic variants among the variants with activity levels lower than 0.8 IU/g Hb. The distribution of the polymorphic variants, in relation to the origin of the subjects studied, differs throughout the country. PMID- 2596829 TI - How much difference does chromosome banding make? Adjustments in prevalence and mutation rates of human structural cytogenetic abnormalities. AB - A collaborative analysis was undertaken of 226 karyotypes with structural chromosome abnormalities diagnosed primarily with low level banding resolution, about 300 to 400 bands per karyotype. We estimate that in this series, use of low level banding was required to detect about 78% of pericentric inversions, about 51% of reciprocal translocations, about 47% of all balanced translocations, about 35% of unbalanced rearrangements other than rings, Robertsonian translocations and extra structurally abnormal chromosomes, about 11% of all unbalanced rearrangements, and about 35% of all structural abnormalities. Adjustment factors derived from these figures were applied to prevalence and mutation rates of structural mutation rates derived from published large scale studies of livebirths. Had low level banding been used in these earlier studies we estimate that the rate of all structural abnormalities would have been about 60% higher than those reported (3.8 per 1000 vs. 2.3 per 1000 in the original studies). The increase is much higher for balanced abnormalities, 75% (3.4 per 1000 vs. 1.9 per 1000), than for unbalanced abnormalities, 5% (0.42 per 1000 vs. 0.405 per 1000). The increase in mutation rates for de novo cytogenetic abnormalities was similarly, considerably higher after such adjustment: the rates per 100,000 gametes increased from 18.0 to 35.0 for balanced rearrangements, from 8.2 to 10.1 for unbalanced abnormalities and from 26.2 to 45.1 for all abnormalities. These estimates illustrate the difference even low level banding makes to detection of structural cytogenetic abnormalities and why contemporary studies using such methods cannot be compared with earlier large scale population studies or livebirths without some type of adjustment such as those suggested here.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596830 TI - Evidence for a human mitotic mutant with pleiotropic effect. AB - Male and female sibs born to third-cousin parents presented with mental retardation, microcephaly, short stature, juvenile onset limb-girdle muscular dystrophy and multiple chromosome mosaicism in lymphocytes and fibroblasts. Different aneuploidies (mostly trisomies) were found in 15-20% of the cells and trisomies for chromosome 8 and chromosome 7 predominated in lymphocytes and fibroblasts respectively, while monosomies were rare. Increased cellular death due to aneuploidy could explain symptoms such as mental and growth retardation and microcephaly. This could be an instance of an autosomal recessive mitotic mutant, possibly affecting a protein simultaneously involved in spindle apparatus and muscle function. PMID- 2596831 TI - Isonymy and migration distance. AB - The distribution of surnames of the living immigrants in the population of the town of Ferrara was studied by sex of immigrants and by distance of their place of origin from Ferrara. It was found that isonymy decreases with distance from the place of origin and that there is sexual dimorphism in migration distance: females migrate preferentially at short distances and males at long and very long distances. As indicators of the abundance of surnames in a distribution, the common ecological indices derived from entropy were used, and compared between migration ranges. It was found that redundancy, like isonymy, decreases with migration distance, and that it may be useful in detecting very-long-distance migration. PMID- 2596832 TI - MAP, an expert system for multiple pairwise linkage analysis. AB - The logic of a program for multiple pairwise linkage analysis under interference is set forth, including a seriation algorithm to obtain a trial order, a mapping bootstrap to improve the trial order, and three procedures for quality control to detect mistyping. This approach is compared with multipoint analysis under null interference, which substantially overestimates map length and cannot incorporate a variety of data. PMID- 2596833 TI - The locus positioning problem. AB - The likelihood method of optimizing the position of loci within a given order using data from pairs of loci is discussed in relation to Fisher's paper of 1922 and to recent data on chromosome 22 in man. PMID- 2596834 TI - Some simple methods for linkage analysis. AB - A method of analysis of suitable many-locus linkage data used by Fisher in 1922 is re-examined in detail, and it is pointed out that it could be used also in human genetics as a simple method for preliminary examination of data. PMID- 2596835 TI - Cross-infection with Pseudomonas aeruginosa in Danish cystic fibrosis patients. PMID- 2596836 TI - Pseudomonas immune globulin therapy improves survival in experimental Pseudomonas aeruginosa bacteremic pneumonia. PMID- 2596837 TI - Pseudomonas aeruginosa pneumonia. Treatment with nonsteroidal anti-inflammatory agents to prevent lung tissue damage. PMID- 2596838 TI - Beta-lactamase inhibitors. PMID- 2596839 TI - A note on the failure of CGP 19835 A (MTP-PE) to influence the course of influenza A2 infection in human volunteers. AB - A single dose of the immunomodulator CGP A (MTP-PE) given intranasally to human volunteers 24 h prior to challenge with influenza A2 virus failed to protect against infection or ameriolate any subsequent illness. PMID- 2596840 TI - Flatulence and other discomforts associated with consumption of cowpea (Vigna unguiculata). AB - Abdominal discomfort after eating cowpeas is known to be a major constraint on their greater consumption. Problems associated with cowpea consumption were identified by questionnaire in 448 randomly selected families. Some (28%) of the respondents had never experienced flatulence. Those who did said it occurred when cowpeas were eaten at all (16.7%), as dinner (42%) or without other foods (15%). A subsample of 40 people who complained of serious abdominal discomfort were fed cowpeas cooked by eight different methods at three consecutive dinners for each method. The problems reported were indigestion, vomiting, diarrhoea, increased belching, bad breath, offensive stool, flatulence, constipation, mild abdominal discomfort and sleepiness. Many respondents complained of mild abdominal discomfort with undehulled cowpeas (72.5%) and dehulled cowpeas (42.5%) that had been cooked at atmospheric pressure. Only 12.5% of the respondents complained of discomfort with dehulled cowpeas cooked under extra pressure. Thus, dehulling resulted in substantial reduction in the frequency and incidence of reported discomforts but pressure cooking also had beneficial effects, probably because of the higher cooking temperature attained. PMID- 2596841 TI - Gastrointestinal correlates of the development of hunger in man. AB - Experiments were carried out on ten healthy male volunteers to investigate the relationship between the return of hunger after a meal and gastric emptying, blood glucose levels and small intestinal motor patterns. There was a significant correlation between the postprandial increase in hunger ratings and the time for 90% of the meal to empty (r = 0.75, p less than 0.02): hunger ratings started to increase in three subjects when over 40% of the food still remained in the stomach, and they continued to increase in all subjects even when the meal had ceased to empty from the stomach. These results suggest the reduction of gastric distension may have a permissive role in the development of hunger after a meal. The increase in hunger was not related to any consistent change in plasma glucose concentration. Finally, the postprandial onset of a fasting motor pattern (phase III-like activity) always occurred when the stomach had emptied more than 80% of its contents and after hunger had increased. Our data are compatible with the hypothesis that the return of hunger is directly related to a decline in the exposure of the upper small intestine to nutrient stimuli, but could be modulated by gastric distension. PMID- 2596842 TI - Limited compensation by table salt for reduced salt within a meal. AB - Sixteen subjects, all of whom had said in a preliminary questionnaire that they normally added table salt to foods, were fed standard meals in the laboratory over 10 days. The meals were identical, except that on 5 days the meal had no added salt (containing 0.46 g sodium chloride) or had salt added to a level of 5.09 g. They were allowed free access to salt pots with the meals and used an average of 1.40 g table salt with the unsalted meal and 0.36 g with the salted meal, thus compensating for 22% of the difference in salt content of the meal. There was no difference in water consumption between the two types of meal. Nutrient intake from the rest of the diet did not differ between periods with high and low salt meals. The failure to compensate more fully for reduced salt in the foods can be attributed to the greater availability of table salt for perception; less table salt than salt incorporated in the foods is therefore required. Reduction of salt concentrations in purchased foods would be unlikely to be fully replaced by the consumer adding table salt. PMID- 2596843 TI - Feed intakes and meal patterns of sheep during pregnancy and lactation, and after weaning. AB - Four cross-bred ewes were kept in individual pens from the last month of pregnancy until the third week of weaning after a 5-week lactation; lambing occurred in late March. The ewes were offered a complete pelleted feed ad libitum, and every few days the feeding behaviour of each was monitored by continuous recording of the weight of the feed container. The weight and timing of each meal was used to calculate mean meal size and length, intermeal interval, hunger and satiety ratios. The increase in daily intake which occurred after parturition was due to increases in meal size, rate of eating and meal frequency. Intake was lower in the period of the day from 0400 hrs to 0800 hrs than during any of the 4-h periods between 0800 hrs and 2400 hrs, with intermediate values at 2400-0400 hrs. The time of day had no effect on meal size or rate of eating. These results are compared with the predictions of a model designed to predict meal occurrences in sheep and the differences used to suggest improvements to the model. PMID- 2596844 TI - Genuinely olfactory preferences conditioned by protein repletion. AB - Effects of protein on mild food deprivation in the rat conditioned a relative preference for an intense, insoluble and tasteless odorant. This learned preference for the protein-paired odorant over a non-nutritive-paired odorant was temporarily obliterated by insertion of tubes in the nares to bypass the olfactory mucosa. This demonstrates truly olfactory conditioning, contrary to assertions that gustatory conditioning had not been excluded. PMID- 2596845 TI - Preparation and properties of RNase T2 immobilized on concanavalin A-sepharose. AB - Partially purified RNase T2 (EC 2.7.7.17) from Aspergillus oryzae was bound through its carbohydrate moiety to Concanavalin A-Sepharose. The retention of activity was high, ranging from 70% at low enzyme load to approximately 9% at high enzyme load. Though there was no change in the pH and temperature optima, the pH stability and the Km decreased after immobilization. Compared to the soluble enzyme, the immobilized RNase T2 showed enhanced temperature stability and more resistance to metal ions. Both soluble and immobilized enzymes were stable to 8 M urea. On repeated use, the bound enzyme retained more than 60% of its initial activity after six cycles. PMID- 2596846 TI - The specificity of interaction between S-adenosyl-L-methionine and a nucleolar 2' O-methyltransferase. AB - The structural features of S-adenosyl-L-methionine (SAM)3 required for optimal binding to a nucleolar 2'-O-methyltransferase were elucidated using various analogs of SAM with modifications of the amino acid, sugar, sulfonium center, and base portions of the molecule. Equilibrium binding constants for SAM and each analog were determined by a nitrocellulose filter binding assay. To ensure the chiral and chemical purity of the 3H-labeled SAM used in the binding experiments, a cation-exchange HPLC procedure was developed to separate degradation products of SAM such as adenine and 5'-deoxy-5'-methylthioadenosine, as well as to separate the (S,S)-SAM from the biologically inactive (R,S)-SAM stereoisomer. Results from these studies demonstrated that S-adenosyl-L-homocysteine, a product of the methyltransferase reaction, bound equally as well as (S,S)-SAM, indicating that neither the charge nor the methyl group at the sulfonium center of (S,S)-SAM is essential for maximal binding. Other modifications of the sulfonium center demonstrated that a sulfur to carbon atom replacement had little effect on binding affinity, whereas substituting an ethyl group for the methyl group greatly reduced the binding affinity. In addition, the chirality at the sulfonium center was important. The naturally occurring S-chiral form had a 10-fold higher binding affinity than the R-chiral form. No significant stereospecificity was observed relative to the chiral alpha-carbon of the methionine moiety in SAM. The alpha-amino group of methionine and the 6-amino group of adenine were both required for maximal binding, while the loss of the 2'-hydroxyl group on the ribose moiety was not. Taken together, these results defined some of the specific geometric and functional group requirements which affect the specificity of interaction between S-adenosyl-L-methionine and the nucleolar 2'-O methyltransferase. PMID- 2596847 TI - Stimulation of cellular alkaline phosphatase activity and its messenger RNA level in a human osteosarcoma cell line by 1,25-dihydroxyvitamin D3. AB - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) significantly stimulated cellular alkaline phosphatase activity in a human osteoblastic osteosarcoma cell line (TE-85 cells) in serum-free medium with 0.1% bovine serum albumin as the hormone carrier in a dose- and a time-dependent manner. The extent of the maximal stimulation was greater and the minimal dose that was required for stimulation was lower than those previously reported for TE-85 cells in the presence of serum. The magnitude of the stimulation of alkaline phosphatase activity by 1,25(OH)2D3 varied with the cell density. Daily changes of conditioned medium, as compared with no medium changes, significantly reduced the magnitude of the stimulation, suggesting that endogenous factors secreted into culture medium could play an enhancing role. Finally, application of Northern blot analysis using an oligodeoxynucleotide probe corresponding to a unique sequence of the human bone/liver/kidney alkaline phosphatase cDNA coding region revealed that 1,25(OH)2D3 increased the alkaline phosphatase mRNA level, suggesting that the increase in alkaline phosphatase activity was a result of either an increase in the rate of transcription or an increase in message stability. PMID- 2596848 TI - Effect of nicotinic acid on microviscosity in mixed liposomal system of lecithin and sphingomyelin. AB - In rat liver plasma membrane, the molar ratio of sphingomyelin and phospholipid is approximately 1:4, whereas, the molar ratio of phospholipid and cholesterol is 3:1. Considering this ratio to be typical for a real biological membrane, we have studied the effect of anticholesterol and the vasodialatory drug nicotinic acid (NA) on the fluidity profile of a liposomal system of lipids mixed in this ratio using the fluorescence polarization probe 1,6-diphenyl-1-1,3,5-hexatriene. The study reveals that when NA is added to the aqueous dispersion of the mixed lipid system (molar ratio of lipid:NA, 1:1) it creates a more fluid environment for the probe molecule and modifies the fluidity profile of the cholesterol-incorporated liposomal system by eliminating the effect of cholesterol to some extent. The drug also affects the activation energy of diffusion of this system. These results on fluidity have been compared with those in cases of liposomes of individual lipids. The effect of NA on fluidity may be attributed to a mechanical interaction of the drug molecules with the lipid molecules. PMID- 2596849 TI - Secondary structure and membrane topology of cytochrome P450s. AB - The secondary structure prediction of 19 microsomal cytochrome P450s from two different families was made on the basis of their amino acid sequences. It was shown that there is structural similarity between the heme-binding sites in these enzymes and those in the bacterial P450cam. An average predicted secondary structure of cytochrome P450 proteins with 70% accuracy contains about 46% alpha helices, 12% beta-sheets, 9% beta-turns, and 33% random coils. In the region of residues 35-120 in microsomal P450s two adjacent beta alpha beta-units (the Rossmann domain), were recognized and may be available to interact with the NADPH cytochrome P450 reductase. Using the procedure for identification of hydrophobic and membrane-associated alpha-helical segments, only one N-terminal transmembrane anchor was predicted. Also the heme-binding site may include the surface-bound helix. A model for vertebrate microsomal P450s having an amphipathic membrane protein located on the cytoplasmic side of the endoplasmic reticulum membrane, with their active center lying outside or on the bilayer border, is proposed. PMID- 2596850 TI - Force-flow and back-pressure relationships in mitochondrial energy transduction: an examination of extended state 3-state 4 transitions. AB - Liver mitochondria were incubated through extended State 3-State 4 transitions (B. Chance and G. N. Williams (1955) J. Biol. Chem. 217, 409-423) in the presence of high concentrations of adenine nucleotides and in presence and absence of a protonophore. In the terminal phase of these transitions (the region of respiratory control), (a) there was a proportional relationship between the phosphorylation potential and membrane potential (delta psi); and (b) the rate of phosphorylation (Jp) was proportionately and inversely related to the back pressure of delta psi (reflective of proton-motive force (delta p); (c) when phosphorylation was limited by the magnitude of delta psi in the presence of increasing [protonophore], Jp was proportionately and directly related to delta psi. The slopes of these two dependencies (a and c) were approximately equal, but opposite in sign. Protonophore or ADP, added separately, decreased delta psi but the extent of decrease in delta psi by ADP added after increasing amounts of protonophore decreased in a manner proportional to Jp. These data are in all respects consistent with bulk-phase delta p being the central intermediate driving (or suppressing) the phosphorylation reaction. PMID- 2596851 TI - Potato tuber succinate semialdehyde dehydrogenase: purification and characterization. AB - Succinate semialdehyde dehydrogenase (SSADH) has been purified from potato tubers with 39% yield, 832-fold purification, and a specific activity of 6.5 units/mg protein. The final preparation was homogeneous as judged from native and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Gel filtration on Sepharose 6B gave a relative molecular mass (Mr) of 145,000 for the native enzyme. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave a single polypeptide band of Mr 35,000. Thus the enzyme appears to be a tetramer of identical subunits. Chromatofocusing of the enzyme gave a pI of 8.7. The enzyme was maximally active at pH 9.0 in 100 mM sodium pyrophosphate buffer. In 100 mM Tris-HCl buffer, pH 9.0, the enzyme gave only 20% of the activity found in pyrophosphate buffer and had a shorter linear rate. The enzyme was specific for succinate semialdehyde (SSA) as substrate and could not utilize acetaldehyde, glyceraldehyde 3 phosphate, malonaldehyde, lactate, or ethanol as substrates. The enzyme was also specific for NAD+ as cofactor and NADP+ and 3-acetylpyridine adenine dinucleotide could not serve as cofactors. Potato SSADH had a Km of 4.6 microM for SSA when assayed in pyrophosphate buffer and was inhibited by that substrate at concentrations greater than 120 microM. The Km for NAD+ was found to be 31 microM. The enzyme required exogenous addition of a thiol compound for maximal activity and was inhibited by the thiol-directed reagents p hydroxymercuribenzoate, dithionitrobenzoate, and N-ethyl-maleimide, by heavy metal ions Hg2+, Cu2+, Cd2+, and Zn2+, and by arsenite. These results indicate a requirement of a SH group for catalytic activity. PMID- 2596852 TI - Rat peptidylglycine alpha-amidating enzyme: the relation between activities at neutral and alkaline pH Values. AB - A substantially high level of alpha-amidating activity at an alkaline pH (8-9.5), often seen as another pH optimum peak in addition to the neutral one, has been observed in various rat tissues. We have also found that crude enzymes from rat brain, pituitary, and small intestine showed a pH profile with two pH optima at neutral pH (6.5-7) and alkaline pH (8.5-9) when D-Tyr-Val-Gly was used as substrate. With a combination of ion-exchange and gel filtration chromatographies, we obtained two fractions, S-1 and S-2, from rat brain; S-1 contained an alpha-amidating enzyme of an apparent molecular weight of 36,000 (36K enzyme) exhibiting a single pH optimum at 8.5. On the other hand, S-2 apparently showed almost no or only marginal activity at either pH 7 or 8.5, but when S-2 was combined with S-1, a neutral pH optimum at 7 could be elicited. The factor in S-2 that was responsible for this combined action was a protein of an apparent molecular weight of 41,000 (41K protein). Both proteins were found to be colocalized in the same subcellular organelle, probably in the secretory granule. It seems likely, then, that the pH profiles characterized by two optimal peaks seen in crude rat enzymes can be attributed to the presence at an appropriate ratio of the 41K protein and 36K enzyme. PMID- 2596853 TI - Allyl alcohol- and acrolein-induced toxicity in isolated rat hepatocytes. AB - Incubation of isolated hepatocytes with allyl alcohol results in GSH depletion and subsequent cytotoxicity which is prevented by pyrazole, an inhibitor of alcohol dehydrogenase. Both GSH depletion and cytotoxicity were much more rapid when hepatocytes were incubated with acrolein, the reactive metabolite, and were not affected by pyrazole. However, cytotoxicity of both allyl alcohol and acrolein was enhanced by the aldehyde dehydrogenase inhibitors cyanamide and disulfiram. Malondialdehyde, a lipid peroxidation product, was also formed when hepatocytes were incubated with either agent, and treatment of the hepatocytes with a ferric ion chelator, desferrioxamine, or an antioxidant delayed the cytotoxicity without affecting GSH depletion. Although no GSSG was formed and addition of disulfide reductant dithiothreitol did not restore GSH levels, cytotoxicity was prevented if dithiothreitol was added some time after either agent. PMID- 2596855 TI - [Intravesical BCG therapy in patients with recurrent superficial bladder tumors]. AB - Intravesical instillation of BCG has recently become a treatment for superficial bladder tumor, and favorable results are reported. We have also obtained favorable results by performing intravesical BCG therapy to totally 32 cases of superficial recurrent bladder tumor and carcinoma in situ (CIS) one indicated for total cystectomy. The subjects were 29 cases of Ta and T1 and 4 cases of Tis, which are classified into 27 cases for treatment and 5 cases for prevention of recurrence after TUR. As the method for administration, 120 or 80 mg of BCG was dissolved in physiological saline and infused intravesically every week a total of 8 times. As a result of designating the patients who received the treatment more than 4 times as the subject, CR and PR were 19 cases (73%) and 5 cases (19%), or respectively, out of 26 assessable cases, and effective rate including PR was 93%. No recurrence has been observed so far in any of 5 cases treated for prevention of recurrence. Side effects which required treatment were observed in 13 cases (41%), but treatment could be continued by symptomatic therapy in most of the cases. Treatment was discontinued in 4 cases, 3 of which were hepatic disorders. It is considered that intravesical instillation of BCG is a therapeutic procedure which is good for trial in future in the light of the great efficacy obtained in the present study. PMID- 2596854 TI - [Combination therapy with etoposide, adriamycin and cisplatin in advanced primary and recurrent gastric cancer]. AB - Fourteen patients with advanced gastric cancer consisting of seven primary cases and seven recurrent cases were treated with the combination of etoposide, adriamycin and cisplatin (EAP). One of the primary cases (14%) and three of the recurrent cases (43%) responded to the therapy, but a high incidence of toxicities including leukopenia, thrombocytopenia, alopecia, nausea and vomiting was observed. It is concluded that EAP therapy can be useful in the treatment of advanced gastric cancer if countermeasures to the toxicities of these drugs are considered. PMID- 2596856 TI - [Treatment of acute leukemia with "MB-triple V" therapy--a comparative study of "MB-triple V" therapy and B-triple V therapy]. AB - Eleven patients with acute leukemia were treated with MB-triple V therapy consisting of mitoxantrone, behenoyl-arabinoside, etoposide, vincristine and vindesine. In this regimen, the target points were set for WBC count in the peripheral blood (less than 1,500/microliters) and TNC count in the bone marrow (less than 15,000/microliters). In this study, we compared the WBC count in nadir state and the duration until WBC count returned to above 1,000/microliters between 11 patients with MB-triple V therapy and 15 patients with B-triple V therapy in which target points were not set. In particular, the standard distribution of WBC count in nadir state of MB-triple V group was significantly smaller than that of B-triple V group. The number of early deaths in the course of MB-triple V (0/11, 0%) decreased compared with B-triple V group (3/15, 20%). Seven patients of the eleven patients with this regimen achieved CR state (63.6%). Hereafter, further cases are necessary before this combination chemotherapy as a part of the induction therapy is evaluated. PMID- 2596857 TI - [Basic study on hepatic artery chemoembolization and tumor selective drug targeting by temperature-sensitive liposome with local hyperthermia]. AB - Temperature-sensitive liposome entrapping adriamycin (L-ADM) was administered into the hepatic artery of hepatic tumor-bearing rats. The embolization of the hepatic artery with liposome and bio-distribution of ADM were examined. ADM concentration in blood showed a peak at 30 min after local heating on tumor (the heating had been performed for 6 min at 41-42 degrees C 2 hr. after injection). The value at the peak was about 3 times higher than that just before heating. ADM administered in liposomal form showed a high accumulative property to tumor with heating; ADM concentration in tumor 8 hr. after administration of ADM in liposomal form was about 5 times higher than that in liver and about 30 times higher than that in the heart, and about 20 times higher than that in tumor after administration in free form. PMID- 2596858 TI - [Combination effects of etoposide with other antitumor drugs in vitro and in vivo]. AB - Combination effects of etoposide (ET) with each of 10 antitumor drugs were examined with P 388 leukemia cells in vitro and in vivo. Median effect analysis was applied for the evaluation of in vitro effect by the growth inhibition, and the in vivo effect by comparison of the increase of life span (ILS) in a combined group with the sum of ILS's in 2 single agent groups. Among 10 drugs combined with ET, cyclophosphamide (melphalan was used for in vitro study), cisplatin and 6-mercaptopurine exhibited a strong synergism both in vitro and in vivo. The combination of ET with mitomycin C, vincristine, vindesine or cytarabine produced additive or slightly synergistic effect in the both systems. However, methotrexate + ET combination showed an antagonistic effect. Although the combination of ET with doxorubicin or fluorouracil showed a slight synergism in vitro, it was antagonistic in vivo. Thus, the in vitro and in vivo combined effects were consistent in 8 of 10 drugs. The employed methods in the present studies could distinguish high efficacy of ET + cyclophosphamide and ET + cisplatin, which are clinically approved as effective combinations against lung cancer. The methods seem to be useful to assess the drug efficacy in experimental combination. PMID- 2596859 TI - [Plasma kinetic study following oral administration of leucovorin tablets in patients with gastric cancer--influence of subtotal gastrectomy]. AB - Patients with advanced gastric cancer were treated with methotrexate-5 fluorouracil sequential therapy. In order to rescue of methotrexate toxicity on the normal proliferating tissue, leucovorin was administered orally to outpatients. As the comparative study, we examined plasma kinetics following oral administration of leucovorin (15 mg) in 6 patients with gastric cancer (received subtotal gastrectomy) and 5 normal subjects. In the patients, peak plasma concentrations of d-1-formyltetrahydrofolate and its main metabolite 5 methyltetrahydrofolate were found after 2 hrs. (7.35 X 10(-7) M, 3.09 X 10(-7) M), and in normal controls also both after 2 hrs. (1.01 X 10(-6) M, 4.89 X 10(-7) M). The active folate metabolite persisted for more than 6 hrs. at over 1 X 10( 7) M that could rescue normal tissue from methotrexate toxicity after leucovorin oral administration in the patients received subtotal gastrectomy. PMID- 2596860 TI - [In vivo antitumor activity of mitoxantrone and the flow cytometric analysis of its influence on cell cycle transition--comparison with doxorubicin and aclarubicin on ascitic hepatoma AH109A cells]. AB - Mitoxantrone was compared with doxorubicin and aclarubicin of its in vivo antitumor activity and influence on cell cycle transition by use of rat ascitic hepatoma AH109A. Antitumor activity determined by the cell growth curve was similar in mitoxantrone and doxorubicin, but the sensitivity of AH109A to aclarubicin was lower than that to the other two drugs. Doxorubicin and mitoxantrone showed all phase arrests with 1/10 of maximally tolerated dose (MTD), and with lower concentrations a strong arrest at G2 phase was observed, thus, mitoxantrone appeared to have a similar antitumor activity on AH109A to that of doxorubicin. Aclarubicin, with 1/10 MTD, demonstrated only a transient arrest at G2 phase, cells arrested at G2 phase entering into the next phase. With below 1/10 MTD, there was no appearance on histograms, and the influence on AH109A cell cycle transition by aclarubicin was considered to be little in comparison with doxorubicin and mitoxantrone. PMID- 2596861 TI - [Effect of adriamycin on cell cycle by bromodeoxyuridine-labeling method]. AB - We studied the effect of adriamycin on DNA synthesizing cells from the view point of cell cycle. DNA synthesizing cells were marked by bromodeoxyuridine, which is a known marker for such cells, before administration of adriamycin. Then, the level of this marker was sequentially measured by flow cytometry. At the low concentration (0.01 micrograms/ml), adriamycin caused delay of the shifting time to the S phase 16 hours after administration. The marked cells were accumulated at the G2M phase at a moderate concentration (0.1 micrograms/ml), and blocked at the S phase at the higher concentration (1.0 micrograms/ml). PMID- 2596862 TI - [A case of advanced bladder cancer successfully treated with intraarterial chemotherapy]. AB - A 79-year-old Japanese male came to our hospital with complaints of protraction and macroscopic total hematuria. The medical imaging methods revealed a large papillary tumor in the left lateral wall of the bladder with the staging of T3N0M0. The pathological diagnosis was transitional cell carcinoma, G3. He received intraarterial chemotherapy with CDDP, ADM and MTX, which was called IA MAC regimen. After two IA-MAC, no medical imaging method could reveal the tumor. The biopsied specimen, which was taken using the transurethral resection of the bladder mucosa, demonstrated no malignant cells. The new chemotherapeutic regimen "IA-MAC" is useful for the treatment of localized advanced bladder cancer in clinical use and enables one to preserve the organ. PMID- 2596863 TI - [An autopsy case of rectal cancer receiving cisplatin at total dose of 3.250 mg and platinum concentrations in autopsy tissue samples]. AB - An autopsy case of a 57-year-old man who had received cisplatin, total dose of 3,250 mg (1,920 mg/m2) after proctectomy for advanced rectal cancer with hepatic metastasis is reported. Platinum concentrations in autopsy tissue samples are also reported. Cisplatin at a dose of 20-40 mg was administered intravenously once a week for 82 weeks, but renal failure did not occur. The patient died 529 days after his last cisplatin therapy, due to acute suppurative cholangitis. On autopsy, the hepatic hilar metastasis involved the bile duct, but the other metastasis of the liver became regeneration and necrosis, and the kidneys showed few findings but congestion and arteriosclerotic change. The spleen evidenced mild hemosiderosis. Tissue samples obtained at the time of autopsy were assayed for platinum using flameless atomic absorption spectrometry. The spleen had the highest concentration, about 2.7 times as high as that of the liver. The liver, the heart and the kidneys had high platinum concentrations (greater than 3.04 micrograms/g), but those of the jejunum and the ileum were low (less than 0.95 micrograms/g). Although cisplatin, FT 207 and krestin were effective for the rectal cancer, platinum was undetectable (less than 0.13 micrograms/g) in the ascending and the transverse colons. PMID- 2596864 TI - Heterosexual transmission of the human immunodeficiency virus: a seroepidemiological study. AB - The transmission of the human immunodeficiency virus (HIV) was studied in 647 subjects who presented no apparent risk factors for the infection other than having had promiscuous heterosexual relations, heterosexual relations with people with an elevated risk of infection, or heterosexual relations with people infected by human immunodeficiency virus. Thirty subjects were found to be seropositive for anti-human immunodeficiency virus antibodies. The elevated risk factors included being the habitual partner of a person at risk of infection or of a person who was infected by human immunodeficiency virus, or being the partner of a patient with acquired immunodeficiency syndrome. The transmission of the virus was verified in 13 of 284 subjects (4.57%) who had had heterosexual intercourse three or more times with persons at risk and in 16 of 101 subjects (15.84%) who had had heterosexual intercourse three or more times with persons who were seropositive for human immunodeficiency virus antibodies. No significant correlation between human immunodeficiency virus infection and a history of sexually transmitted infections, nor between human immunodeficiency virus infection and female subjects was found. These data suggest that the epidemic of acquired immunodeficiency syndrome can also spread through heterosexual relations, even if the possibility of becoming infected in this way seems at the moment limited to particular risk behaviors. PMID- 2596865 TI - Sweating patterns in atopic dermatitis patients. AB - Postganglionic sweat output in ten patients with atopic dermatitis was determined by a quantitative sudomotor axon reflex test in which the output results from axon reflex stimulation by acetylcholine iontophoresis. All measurements were obtained from normal skin on the volar aspect of the left wrist and dorsal aspect of the left foot of the atopic patients. Latency, sweat volume, and dynamic sweat pattern were variables included in the study. An abnormal value or configuration was found in nine of the ten patients studied. Seven of the ten patients had abnormal sweat output values. Atopic patients have abnormal sweating patterns, which may be inherently responsible for or related to their disorder. PMID- 2596866 TI - Mitogenic activities for skin fibroblasts in the sera from untreated scleroderma patients at the early stage. AB - Mitogenic activities for adult skin fibroblasts in 17 sera from untreated patients with scleroderma at the early stage were studied. Mitogenic activities in 10% test sera were measured by the [3H]-thymidine incorporation assay using confluent fibroblasts; there was no significant difference between scleroderma affected and normal controls. Growth-stimulatory activities for subconfluent fibroblasts in 10% test sera were measured by increased cell numbers; again, there was no significant difference between scleroderma-affected and normal controls. There have been contradictory reports on growth-stimulatory activities in scleroderma sera; our data do not suggest the presence of a specific mitogen in scleroderma sera. PMID- 2596867 TI - Absence of tumor necrosis factor-alpha in suction blister fluids and stratum corneum from patients with psoriasis. AB - Tumor necrosis factor (TNF)-alpha is a cytokine with multiple biological properties, particularly proinflammatory, apart from the induction of tumor necrosis. In order to elucidate the role of TNF-alpha in the pathogenesis of psoriasis, we have carried out bioassay and enzyme-linked immunosorbent assay for TNF-alpha in suction blister fluids and horny tissue extracts from psoriatic skin. Although bioassay showed some activities in the suction blister fluids and horny tissue extracts, there were no significant differences between the levels of activities from normal and psoriatic skin. They were at the background level and pretreatment of the samples with anti-TNF-alpha antiserum failed to abrogate the activities. ELISA confirmed the absence of TNF-alpha. Therefore, the present study could not verify that TNF-alpha plays a major role in the pathogenesis of psoriasis. PMID- 2596869 TI - Cutaneous reactions to kallikrein and histamine in patients with urticaria. PMID- 2596868 TI - Effect of retinoids on wound healing in diabetic rats. AB - In order to clarify the effect of retinoids on wound healing, diabetic rats were treated with oral acitretin or isotretinoin at 1 mg/kg for 5 days prior to the setting of deep punch biopsies, 6 mm in diameter, and for 14 days thereafter. Wound care was done with either a dry or a wet dressing. Wound surface area and transepidermal water loss were measured twice weekly at the time of the change of dressings. Statistically significant increases of both test parameters were noted after 1 week in retinoid-treated animals, but only with dry dressings. No excessive granulation tissue was observed at any time. The data suggest that under certain unfavorable circumstances, problems in wound healing may arise under retinoid treatment. PMID- 2596871 TI - Yet another form of deinstitutionalization. PMID- 2596870 TI - Immunohistochemical localization of heparan sulfate-containing proteoglycan in normal human skin with monoclonal antibodies: comparison with that of fibronectin. PMID- 2596872 TI - Causal explanations and emotional health of women during divorce. AB - This study investigated (a) relationships between women's causal explanations for divorce and their present emotional health, and (b) the clinical usefulness of the Personal Stress Inventory (Ireton, 1980) as a stress assessment tool. The convenience sample consisted of 36 women ending a first marriage. Subjects were interviewed using the Tennessee Self-Concept Scale (Fitts, 1965), the Personal Stress Inventory, and a causal explanations questionnaire. Results indicated that causal explanations did predict self-esteem and emotional distress under conditions suggested by the reformulated learned helplessness model. The Personal Stress Inventory includes an emotional distress subscale that predicted self esteem, self-perceptions of coping ability, and overall concerns about wellness/energy. PMID- 2596873 TI - Longitudinal analysis of hope in community-based older adults. AB - Clinicians usually agree that hope helps older persons to cope with stressful life events and changes in their life, and that hope may even affect their health. However, little research has examined whether hope functions as a psychosocial factor in modifying the relationship between stress and health. Older adults experience many events, which may make them more vulnerable than younger persons to loss of hope. These events may involve changes in their health, roles, self-concept, social support, housing, and income. If we know how these events affect hope, we may be able to detect and avert lapses in hope among our older patients, and even shape interventions that enhance hope. PMID- 2596874 TI - Human immunodeficiency virus and mental health: meeting the needs of health professionals. AB - Psychiatric-mental health nurses are taking a leadership role in the human immunodeficiency virus epidemic. This article details activities, developed through federally-supported acquired immune deficiency syndrome (AIDS) projects, which are designed to meet the mental health needs of health professionals who work intensively with people with AIDS. PMID- 2596875 TI - New conceptions of care, community, and chronic mental illness. AB - This article reports on the author's observations as a member of the National Advisory Committee to the Robert Wood Johnson Program for the Chronically Mentally Ill (CMI). The article highlights the needs of large city mental health systems, which serve the CMI, employing the concepts of centralization and continuity, as well as financing, housing, and support services reform. The implications for psychiatric mental health nursing are discussed. PMID- 2596876 TI - Revision of the phenomena of concern for psychiatric mental health nursing. AB - The purpose of this article is to provide an update on the progress of the American Nurses' Association task force to identify the phenomena of concern for psychiatric mental health (PMH) nursing practice and to propose future directions for the development of PMH nursing specialty diagnoses. This and the two articles that follow were written with the intent of providing information that could be used by PMH nursing clinicians, educators, administrators, and researchers to elaborate, test, revise, and apply work already begun to advance PMH nursing practice. PMID- 2596877 TI - Clinical application of human responses classification system: child example. AB - The "Classification of Human Responses of Concern for Psychiatric-Mental Health Nursing Practice" is a useful instrument for clinical practice. It provides a systematic method of organizing and labeling human responses that are of interest for psychiatric nurses. Furthermore, the human response classification system provides a foundation for planning nursing interventions and a format for communicating identified nursing problems. The purpose of this article is to describe how the human response classification system can be utilized in clinical practice. PMID- 2596878 TI - Field trials of the phenomena of concern for psychiatric/mental health nursing: proposed methodology. AB - An important step in the development of the American Nurses' Association (ANA) Task Force's Classification of Phenomena of Concern for Psychiatric/Mental Health Nursing is a plan for conducting field trials to determine interrater diagnostic reliability using the classification system. The ANA Task Force identified field testing as stage two in a three-stage process for completion of our work. In this article, we identify methodologic directions that will allow us to answer two important questions. First, what is the interrater reliability of the system of psychiatric nursing diagnoses when applied to clients by psychiatric/mental health nurse clinicians in their practice, and second, how do the clinicians who use this system view its usefulness for planning and evaluating nursing care? PMID- 2596880 TI - Reform of the British health services: how will it affect services for people with rheumatic diseases? PMID- 2596879 TI - Schizophrenia in the elderly: what nurses need to know. PMID- 2596881 TI - Osteoarthritis of the knee joint: an eight year prospective study. AB - Thirty one patients (25 women, six men, mean age 71.7 years) with established osteoarthritis (OA) of the knee were examined clinically and radiologically on two occasions, eight years apart. Four patients thought they had got better, two of whom had striking functional improvement. Seven remained the same and 20 patients got worse, two needing knee surgery and many developing severe disabilities. Most of the patients had a history of slow acquisition of OA at new joint sites, hand disease emerging as the commonest other site of involvement. Changes in symptoms, disability, and radiographs did not correlate. Three of the four patients who improved symptomatically lost range of motion at the knee and developed more severe changes on their radiographs. Chondrocalcinosis of the knee was seen in five patients, including two of those who improved. PMID- 2596882 TI - Localisation of lysozyme mRNA in rheumatoid synovial membrane by in situ hybridisation. AB - Type A synovial lining cells have been shown to contain lysozyme in their lysosomes. This might be phagocytosed because synovial fluid contains lysozyme originating from tissue macrophages and articular cartilage but in arthritides, in particular, from neutrophils. In situ hybridisation with 35S labelled cDNA was used to detect mRNA for lysozyme over synovial lining in patients with rheumatoid arthritis. No hybridisation was found with lactoferrin cDNA, which was used as a negative control. Computer search against the EMBL gene bank (release 14) did not show any significant cross hybridisation to a known sequence. In cytological specimens 35S-cDNA:mRNA hybrids were observed in positive but not in negative control cells. The presence of lysozyme and its mRNA suggests that type A synovial lining cells are of mononuclear phagocyte lineage. PMID- 2596883 TI - Ankylosing spondylitis--experience with a self administered questionnaire: an analytical study. AB - A questionnaire drafted by the president of a self help group of patients suffering from ankylosing spondylitis (AS), the Danish Ankylosing Spondylitis Society (DASS), was completed by 179 of 184 (97%) consecutive patients with AS. The following results were found. The diagnosis of AS was delayed an average of 12.6 years for women and 9.5 years for men. No differences were found in age at onset of the disease. A comparison of juvenile and adult onset showed a higher incidence of initial peripheral articular manifestations in patients with juvenile ankylosing spondylitis. Stiffness progressed significantly in both sexes during the illness. Two men still had stiffness localised only to the lumbar spine after more than 20 years of illness. Twenty four of 47 women (51%) and 36/121 (30%) of the men had experienced extra-articular disease. Fifteen of 46 women (33%) and 18/121 (15%) of the men had iritis and conjunctivitis before the diagnosis of AS was established and later, in the course of the illness. The results of this study agreed with those of previous investigations. The advantage of using a questionnaire as a screening test is that many patients may be studied and information brought up to date in a simple and inexpensive way. PMID- 2596884 TI - B cell lymphokines in human systemic lupus erythematosus. AB - B lymphocytes of patients with systemic lupus erythematosus were studied to determine if they were intrinsically hyperresponsive to lymphokine mediators. Peripheral blood B cells from 25 lupus patients and 16 normal individuals matched for age and sex were cultured with recombinant lymphokines. B cells both from patients and normal subjects did not show increased [3H]thymidine uptake when cultured with interleukins 1, 2, and 4. The addition of Staphylococcus aureus Cowan I as costimulant increased [3H]thymidine uptake by B cells of patients and normal subjects. In the absence of T cells these recombinant lymphokines did not increase in vitro IgG or IgM production by lupus or normal B cells. Other recombinant lymphokines, interleukin 3, interferon gamma, lymphotoxin, tumour necrosis factor, and colony stimulating factors for granulocytes and macrophages were tested on lymphocytes from smaller numbers of patients and controls. Most patients in this study had inactive disease and all data suggested that B cells from patients with inactive lupus were not hyperresponsive to the lymphokines tested. In addition, the use of lymphokine gene probes for interleukins 2, 3, and 4 did not show spontaneous expression of these genes in circulating lymphocytes. PMID- 2596886 TI - Disease assessment in rheumatoid arthritis. PMID- 2596885 TI - Liver abnormalities and liver membrane autoantibodies in systemic lupus erythematosus. AB - The hepatic involvement of 57 patients with systemic lupus erythematosus (SLE) was studied with special reference to liver membrane autoantibody (LMA). Liver abnormalities were found predominantly in patients with active SLE (27/48 (56%) in active SLE v 3/20 (15%) in inactive SLE). They were, however, rather mild or moderate and tended to disappear as the disease activity of SLE decreased. In this respect the liver abnormalities observed in this study differed from those in patients with lupoid hepatitis. The incidence of LMA in active SLE (8/11 (73%] was significantly greater than that in inactive SLE (4/12 (33%)). The mean LMA index value in active SLE was 8.3, which was also greater than the 2.9 in inactive SLE. Furthermore, in active SLE the mean LMA titre was significantly higher in patients with liver abnormalities than in those without. These results suggest that LMA may be associated with the activity of SLE and may be one of the factors which cause transient liver abnormalities. PMID- 2596887 TI - Phospholipase A2 and inflammation. PMID- 2596888 TI - Development of morphoea in rheumatoid arthritis treated with penicillamine. PMID- 2596889 TI - Inflammation of the uveal tract as a presenting feature of temporal arteritis. PMID- 2596890 TI - Disease remission in rheumatoid arthritis. PMID- 2596892 TI - [Nerve autografts. Various technical approaches]. PMID- 2596891 TI - [Nerve grafts. Anatomy of the donor sites]. PMID- 2596893 TI - [Vascularized nerve trunk grafts. Technic and results of 27 cases]. PMID- 2596894 TI - [Direct muscle innervation]. PMID- 2596895 TI - [Frozen nerve allografts. An experimental study in the rat]. PMID- 2596896 TI - [Nerve expansion]. PMID- 2596898 TI - [Tunnel syndromes and blood glucose anomalies]. AB - The fasting blood glucose was studied in 406 patients with carpal tunnel syndrome. We found 3.3% patients with diabetes mellitus and 15% with abnormal blood glucose levels. A prospective study was performed in 36 patients (oral glucose tolerance test, and blood lipid parameters). 45% of the patients in this group had an abnormal OGTT and 52% presented with hyperlipoproteinemia. PMID- 2596897 TI - [Blast injuries of the 1st commissure]. AB - Explosions are responsible for severe hand injuries. Due to their extremely important functional role, lesions of the thumb and first commissure must be identified separately during assessment of the lesions. No classification of these injuries has been proposed since the one defined by Mac Gregor and Jackson. Based on their experience of 11 injuries, the authors propose a classification divided into four stages of increasing severity. In the emergency situation, the severe forms with disruption of the blood supply have a very poor prognosis. In the other forms, the degree of opening of the first commissure is of fundamental importance. Secondarily, the functional prognosis of the hand is dominated by retraction of the first commissure, ankylosis of the trapezo-metacarpal joint or its preservation during amputations. PMID- 2596899 TI - [Acute ischemia of the fingers]. AB - Chronic vascular insufficiency of the fingers may turn in acute ischemia with cold. The authors report three cases. The first patient showed on his forefinger a distal thrombosis of the ulnar collateral artery and a very thin radial collateral artery. The second patient has interruption of both indicis collateral arteries. The third patient presented an ischemic fifth finger secondary to a distal ulnar artery stenosis. All of the patients complained of pain, numbness, cyanosis or necrosis of the tip aggravated by cold. Laboratory and vascular investigations included digital Allen Test, plethysmography, Doppler examination, axillary block and angiography. The cause may be local and easily cured by surgery, but sometimes the vasospastic component is predominant. If stopping smoking, vasodilators and calcium-inhibitors are ineffective, Flatt has proposed distal digital artery sympathectomy. PMID- 2596900 TI - [Early passive mobilization in surgery of the hand]. AB - The authors present their experience of early passive mobilisation in hand surgery, by a continuous-cycle motorized device. This method of treatment has been applied to various pathological conditions (post-operative management following such operative procedures as stable osteosynthesis of fractures of the long bones, tenolysis and teno-myolysis, arthrolysis and treatment of complex trauma of the hand), demonstrating very good efficacy. This device allows continuous passive mobilisation of the fingers and represents useful complement in the rehabilitation program of the hand. PMID- 2596901 TI - Hydrazide antidepressants possess novel antileishmanial activity in vitro and in vivo. AB - The hydrazide monoamine oxidase inhibitor antidepressants possess a novel antiparasitic action against visceral and cutaneous strains of Leishmania. In vitro, phenelzine was the most active compound tested, while in vivo, nialamide was more potent, and was also effective when applied topically to cutaneous lesions. Despite the coincidence of tricyclic antidepressants also possessing antileishmanial activity, the evidence suggests that the antiparasitic action of the hydrazides is unrelated to either monoamine oxidase inhibition or CNS effects. PMID- 2596902 TI - The epidemiology of Echinococcus granulosus in Great Britain. V. The status of subspecies of Echinococcus granulosus in Great Britain. AB - Twenty-five years ago Williams and Sweatman suggested that in Great Britain there are two subspecies of Echinococcus granulosus--E. granulosus granulosus and E. granulosus equinus. Echinococcus granulosus granulosus does not mature either in foxes or in horses: E. granulosus equinus will mature in either. The prepatent period of E. granulosus granulosus in the definitive host is about 42 days while that of E. granulosus equinus is about 70 days. Each subspecies has a characteristic morphology. More recently, in the course of seven experiments, dogs, red foxes (Vulpes vulpes crucigera), arctic foxes (Alopex lagopus), badgers (Meles meles), domestic ferrets and domestic cats have been infected with protoscoleces derived from hydatid cysts of human, equine and ovine hosts from different regions of England and Wales. Transmissions to horses and sheep were always succeeded by the development of viable hydatid cysts; transmissions to dogs and foxes, by the development of gravid adults. The prepatent period in both dogs and foxes was invariably about 70 days (or longer) and the morphology of all the adult parasites in these definitive hosts was characteristic of E. granulosus equinus. All the evidence derived from these experiments supports the view that there is, in Great Britain, but one subspecies of E. granulosus. That one subspecies is E. granulosus equinus. It infects dogs, red foxes, arctic foxes (experimentally), cats (experimentally), humans, sheep, goats, horses, donkeys, pigs, cattle, roe deer and reindeer (in Scotland). Attempts to transmit E. granulosus to badgers and domestic ferrets were unsuccessful. Of 123 cats infected with protoscoleces of horse origin, one gravid adult parasite was recovered from one animal. PMID- 2596903 TI - Uptake of bacteria by trophozoites of Giardia duodenalis (Say). AB - Rod-like bacteria were found in the cytoplasm of trophozoites of Giardia duodenalis (Say) in domestic rats (Rattus rattus). These structures were always in phagocytic vacuoles without signs of bacteria digestion or degradation of the trophozoite cytoplasm. The uptake of the bacteria was observed from their attachment to the trophozoite membrane until their total incorporation by phagocytosis. PMID- 2596904 TI - Prevalence and seasonal fluctuations of intestinal parasitic infections in the Nablus area, West Bank of Jordan. AB - A total of 22,970 stool specimens collected from patients attending the Central Medical Laboratory in the city of Nablus in the period of 1981-1986 were examined for intestinal parasites. Of these 7412 (32.3%) were positive. Entamoeba histolytica (22.9%), Giardia lamblia (7.3%), and Ascaris lumbricoides (5.7%) were the most prevalent intestinal parasites found. Other intestinal parasites present included Hymenolepis nana, Trichomonas hominis, Trichuris trichiura, Taenia saginata, Enterobius vermicularis and Strongyloides stercoralis. Seasonal occurrence of intestinal parasites in the West Bank of Jordan was also studied in the period January 1981-August 1987. Lower prevalence rates of intestinal parasites generally occurred during winter and early spring. Peak incidence occurred during summer and early autumn. The reasons for these seasonal variations are discussed. PMID- 2596905 TI - Prevalence of Toxocara ova in some schools and public grounds in northern and central Jordan. AB - Two hundred and twenty-six soil samples were collected from school playgrounds and public places in four cities and 17 villages in northern and central Jordan. Toxacara eggs were found in 35 (15.45%) of the samples. Viable eggs were found in 18 samples, with viability ranging from 20 to 78%, and among these 18 samples the mean number of viable eggs per 5 g soil was 5.5 +/- 4.58 S.D. (range one to 15 eggs). Nine of 94 samples collected from public places and five of 86 samples collected from schools contained Toxocara eggs. Viable eggs were found in higher proportions of soils collected from villages around Jerash (three of 21) and Irbid (five of 44), and from Yarmouk University campus (four of 37), than of soils collected from cities (six of 124), but the differences are not significant (P less than 0.05). Eggs of Taenia spp., Hymenolepis diminuta and Ascaris lumbricoides were also recovered, in 34, 15 and nine samples respectively of the 226 examined. PMID- 2596906 TI - Correlation between the infection rate of the vector tick, Haemaphysalis longicornis and the parasitaemia of cattle infected with Theileria sergenti. AB - The infection rate of Theileria sergenti in salivary glands of nymphal Haemaphysalis longicornis which had dropped from cattle showing different piroplasm parasitaemias was examined by the methyl green-pyronin staining method. The results suggested that there was some correlation between parasitaemia and the subsequent infection rate in salivary glands of ticks. It seemed possible that the parasitaemia in cattle, especially the number of parasitized erythrocytes in blood imbibed by ticks, might be an important influence on the number of infected acini of ticks. PMID- 2596907 TI - Simulium (Edwardsellum) squamosum kitetense ssp. n., a new chromosomal and morphological subspecies within the Simulium damnosum complex from east Zaire. AB - A new subspecies within the Simulium damnosum complex is described from the Lualaba river, East Zaire, on the basis of polytene chromosome analysis and larval morphology, under the name Simulium (Edwardsellum) squamosum kitetense ssp. n. Chromosomally it is most similar to S. squamosum, from which it differs by three new fixed inversions. Morphological differences include a reduced number of rays on the premandibular fans, the particular aspect of the combs on those rays, and the general colour of the body which is a very light yellow. A second population from a nearby river was morphologically and chromosomally quite different, although more samples are needed to clarify its taxonomic position. PMID- 2596908 TI - Early bypass operation after acute myocardial infarction. PMID- 2596909 TI - Cerebral blood flow during cardiopulmonary bypass: some new answers to old questions. PMID- 2596910 TI - It is time for a national cardiothoracic surgical data base. PMID- 2596911 TI - Long-term survival after postinfarction bypass operation: early versus late operation. AB - A study of 832 patients operated on within 30 days of infarction from 1974 to 1987 has resulted in 2,388 patient-years (maximum, 14 years) of prospectively acquired follow-up. This study excludes 74 patients in whom cardiogenic shock was the indication for operation. Five-year survival (+/- standard error) was 84% +/- 2%, 85% +/- 1%, and 90% +/- 1%, and 10-year survival was 71% +/- 4%, 68% +/- 1%, and 78% +/- 1% for patients with acute infarction, remote infarction, and no previous infarction, respectively. Age and left ventricular end-diastolic pressure significantly affected long-term survival for patients with acute infarction by both univariate and multivariate analysis. For patients aged less than 65 years, the 5-year and 10-year actuarial survival rates were 89% +/- 2% and 80% +/- 4%, compared with 75% +/- 3% and 58% +/- 9%, respectively, for patients aged more than 65 years. The survival percentages were 89% +/- 2% and 75% +/- 6% for patients with left ventricular end-diastolic pressure less than 15 mm Hg compared with 77% +/- 5% and 67% +/- 7% for patients with left ventricular end-diastolic pressure greater than 15 mm Hg. Operative mortality was 7.6% for patients operated on within 24 hours, compared with 4.1% for patients operated on between 2 and 30 days after infarction. Ten-year survival was similar (about 70%) for all timing groups. Based on these long-term results, there appears to be little to gain by delaying coronary artery bypass grafting, when indicated, after infarction occurs. PMID- 2596912 TI - Elevated hemidiaphragm after cardiac operations: incidence, prognosis, and relationship to the use of topical ice slush. AB - We have reviewed chest roentgenograms of 745 patients before hospital dismissal after cardiac operations and serially to determine the incidence and prognosis of elevated hemidiaphragm and any relationship to the use of topical ice slush (TIS) in myocardial preservation. All patients had similar myocardial preservation techniques including moderate systemic hypothermia and 4 degrees C saline solution poured over the heart at aortic clamping. During a 12-month period, TIS was added to the saline bath. Two (2.4%) of 84 patients before TIS and 5 (2.5%) of 201 consecutive patients operated on since discontinuing TIS had elevated hemidiaphragm on the predismissal roentgenogram. Of 460 patients in whom TIS was employed, 109 (23.7%) had elevated hemidiaphragm (p less than 0.001). When TIS was employed, elevated hemidiaphragm developed in 72 (26%) of 280 patients without internal mammary artery takedown versus 13 of 33 patients (39.4%) with takedown of the internal mammary artery (p = 0.047). Ninety-nine patients with elevated hemidiaphragm were available for follow-up at 1 month, at which time 79 (79.8%) continued to have elevated diaphragm. At 1 year, 14 (21.9%) of 64 patients had persistent diaphragm elevation. We conclude that TIS predisposes to elevated diaphragm and that the incidence is increased when the internal mammary artery is harvested. PMID- 2596913 TI - Use of azygos vein as interposition graft for surgical unifocalization of pulmonary blood supply. AB - Hemodynamic repair in patients with pulmonary atresia, ventricular septal defect, hypoplastic pulmonary arteries with arborization defects, and major aortopulmonary collaterals necessitates prior unifocalization of pulmonary artery blood supply. When direct anastomosis between these collateral vessels and the central pulmonary arteries is not technically feasible, an interposition graft is required. Dacron, polytetrafluoroethylene, and pericardium have been used for this purpose. We describe our experience with the use of azygos vein as an interposition graft in 3 patients who underwent unifocalization of the pulmonary blood supply to the right lung. Our experience suggests that the azygos vein is a useful graft for use in this specific form of unifocalization procedure. PMID- 2596914 TI - Effect of transannular patching on outcome after repair of tetralogy of Fallot. AB - Among 814 patients undergoing repair of tetralogy of Fallot with pulmonary stenosis between 1967 and May 1986, transannular patching in the current era was a weak risk factor for death early postoperatively (predicted 30-day mortality, 4% with a transannular patch and 1.4% without) and is not a risk factor for instantaneous risk of death late postoperatively (predicted 20-year survival including early death, 94% with a transannular patch and 96.5% without). Ninety six percent of surviving patients were in New York Heart Association functional class I at last follow-up, and the slight decline in this percentage as the interval between operation and last follow-up lengthened could have been due to chance alone (p = 0.24) and was no different in patients with a transannular patch. Transannular patching was a risk factor for reoperation for pulmonary regurgitation late postoperatively, but only a 7% incidence within 20 years is predicted when mild residual stenoses are beyond the patch: the incidence rises to about 20% with important distal stenoses. Inferences from the study are relevant to the indications for transannular patching and insertion of allograft semilunar valves at the time of repair. PMID- 2596915 TI - Coronary arterial and sinusal anatomy in hearts with a common arterial trunk. AB - Eighty-four specimens of common arterial trunk were studied with special reference to the arrangement of the leaflets in relation to the atrioventricular valves, the origin of the coronary arteries in relation to the arterial sinuses, and the epicardial course of the coronary arteries. Fourteen normal hearts were used for comparison. In the hearts with common arterial trunk, the location and level of the coronary artery orifices (as well as the relationship of the truncal root to the area of fibrous continuity with the mitral valve) are different from those in normal hearts. In none of the hearts with common arterial trunk (particularly the 53 hearts with three leaflets in the truncal valve) did the appearance of the truncal valve approximate that of a normal aortic valve. Among the 22 hearts with four leaflets, there was a high incidence of coronary artery orifices in opposite sinuses (17/22 or 77.3%) and a low incidence of coronary artery orifices in adjacent sinuses (2/22 or 9.1%). These results suggest that the formation of the truncal valve is independent of the formation of the coronary orifices. Its leaflets are not predestined to become part of either the aortic valve or the pulmonary valve. PMID- 2596916 TI - Operation for acute postinfarction mitral insufficiency using continuous oxygenated blood cardioplegia. AB - Patients with acute-onset mitral insufficiency and cardiogenic shock after myocardial infarction have a high incidence of operative death and morbidity. Patients with ventricular dysfunction, myocardial ischemia, and limited cardiac reserve undergoing an urgent operation represent a challenge to modern methods of myocardial protection. To improve results of operation a new technique was devised with continuous infusion of cold oxygenated blood cardioplegia during the entire cross-clamp period. Between 1984 and 1988, 19 consecutive patients with severe mitral regurgitation and cardiogenic shock (systolic blood pressure less than 60 mm Hg) after myocardial infarction underwent urgent myocardial revascularization, mitral valve replacement, or both. Left ventricular ejection fraction was less than 40% in 16 of 19 patients. All patients had suffered myocardial infarction within 4 weeks of operation and underwent an urgent operation within 24 hours of the onset of hemodynamic compromise. Severe three vessel coronary artery disease was present in 16 of the 19 patients. A continuous infusion of blood cardioplegia was instituted at aortic cross-clamping and continued throughout the cross-clamp period. Infusion of continuous blood cardioplegia was also instituted through each completed distal vein graft. Myocardial septal and left ventricular apical temperatures were maintained at 10 degrees +/- 2 degrees C throughout the cross-clamp period. There were two in hospital deaths (mortality, 10.5%) and low output syndrome was present in 10 patients (53%). At a mean follow-up of 2.5 years, there was one late death and 14 of the 16 remaining patients were in New York Heart Association functional class I or II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2596917 TI - Thrombectomy of the Bjork-Shiley prosthetic valve revisited: long-term results. AB - Thrombotic obstruction of the Bjork-Shiley prosthetic valve is a catastrophic complication, often leading to a fatal outcome. Worldwide experience with the Bjork-Shiley valve supports the need for long-term anticoagulation to prevent entrapment of the disc. Replacement of the malfunctioning device is associated with a high mortality, and therefore a more expeditious method is desirable. It is our experience that simple thrombectomy may suffice in most occasions, even for the mitral position, and especially when done through a bicameral approach in order to visualize both supravalvular and infravalvular regions. The philosophy and results with thrombectomy and disc rotation in 12 cases of thrombotic occlusion of the Bjork-Shiley valve are described. It is suggested that this method may be preferable to replacement of the thrombosed prosthetic valve in select patients. PMID- 2596918 TI - Effects of atrial cardioplegia on the ischemic right ventricle after acute coronary artery occlusion and reperfusion. AB - Right atrial cardioplegia has been advocated as a simple method of delivering retrograde cardioplegia. Passive distention of the right heart inherent with right atrial cardioplegia has been shown to impair right ventricular function in a canine model of global ischemia. This study was designed to compare right ventricular performance after right atrial cardioplegia administered intermittently (n = 5) and continuously (n = 5) with coronary sinus retrograde cardioplegia (n = 5) and aortic root cardioplegia (n = 8) in a canine model of acute right ventricular ischemia and reperfusion. Right ventricular performance was assessed using the load-independent relationship of end-systolic pressure versus dimension (myocardial fiber length). Right ventricular performance was well preserved after reperfusion in those dogs protected with intermittent right atrial cardioplegia (95% of control). Results with continuous right atrial cardioplegia (66% of control) and coronary sinus retrograde cardioplegia (40% of control) demonstrated diminished postreperfusion right ventricular performance. Right ventricular performance in the group protected with aortic root cardioplegia was significantly impaired after reperfusion when compared with all retrograde groups (34% of control, p less than 0.05). In this model, postreperfusion right ventricular performance was preserved in the right atrial cardioplegia groups despite passive ventricular distention. All methods of retrograde cardioplegia resulted in superior preservation of right ventricular performance when compared with standard aortic root cardioplegia. PMID- 2596919 TI - Simplified method for reoperation on the mitral valve. AB - Reoperation on the mitral valve is becoming more common because of the degeneration of bioprosthetic valves, endocarditis, and malfunction or thrombosis of mechanical valves. We advocate a technique that transforms a technically difficult operation into one that is much less tedious, time-consuming, and dangerous than reopening a sternal-split operative site the second, third, or fourth time. Favorable experience in 11 patients using right anterolateral thoracotomy without aortic or right atrial cannulation and without aortic cross clamping or cardioplegia is presented. PMID- 2596920 TI - Large animal model of left ventricular aneurysm. AB - In 28 Dorsett sheep, ligation of the distal homonymous (equivalent to human left anterior descending) and second diagonal coronary arteries produced a constant transmural infarct of 22.9% +/- 2.5% (mean +/- standard deviation) of the left ventricular mass. Serial left ventriculograms showed that within four hours the infarct segment expands, wall thickness decreases, and aneurysmal dilatation occurs and progresses over the next 60 days in all sheep. Epicardial ventricular point references indicated that adjacent noninfarcted myocardium participates in the formation of the aneurysm. Anatomy of the coronary vasculature was studied in 22 excised sheep hearts. In sheep, coronary arterial anatomy is remarkably constant. The left coronary artery provides all of the blood supply to the left ventricle and septum and only a small rim of both the anterior and posterior right ventricles. Cardiac veins from the left ventricle drain into the coronary sinus, which also receives the left azygos vein. Right ventricular veins drain separately. The essentially separate coronary circulations to the two ventricles, the paucity of coronary collateral circulation, and the consistent evolution of left ventricular infarcts into aneurysms are important advantages of the ovine model for both metabolic and ventricular mechanical studies of acute myocardial infarction and left ventricular aneurysm. PMID- 2596921 TI - Tracheobronchial rupture due to blunt chest trauma: a follow-up study. AB - From 1970 to 1988, 9 patients were treated for tracheobronchial rupture arising from nonpenetrating thoracic trauma. All patients had dyspnea and pneumothorax. Four patients had rupture of the right main bronchus, 3 had rupture of the left main bronchus, 1 had rupture of the right intermediate bronchus, and 1 had rupture of the trachea. Four patients were operated on within 24 hours. Three of them had a massive air leak into the suction drainage and underwent thoracotomy. The fourth patient presented difficulties with endotracheal intubation and required a collar incision. Primary reconstruction was performed in all 4 patients. Five patients had a delay of nine to 89 days before operation. All of them had good primary healing but later developed dyspnea. Bronchoscopy revealed scar obstruction in all 5. The stenosed segment was resected in 4 patients at thoracotomy. The fifth patient, who had an intermediate bronchus rupture, underwent lobectomy. Seven patients were followed from 6 months to 18 years. One of them, who had a nine-day delay in treatment, needed further operation 6 months after the accident because of scar obstruction. The other 6 patients were interviewed, examined, and studied with spirometry, body plethysmography, bronchoscopy, and bronchography. In these 6 patients no stricture was seen, and there was no reduced pulmonary function due to the rupture even when operation was delayed. PMID- 2596922 TI - Percutaneous cricothyroidostomy (minitracheostomy) for bronchial toilet: results of therapeutic and prophylactic use. AB - In the period 1984 to 1988, 2,448 patients underwent major thoracic operations in our unit. Of these patients, 144 (5.9%) underwent percutaneous cricothyroidostomy (minitracheostomy) using a 20F pediatric silver tracheostomy tube. Minitracheostomies were performed for the treatment of sputum retention in 81 patients, prophylactically in 62 patients, and as a route for high-frequency jet ventilation in 1 patient. Minitracheostomy tubes remained in situ a median of four days. Suction function was satisfactory in 99% of patients, with only 2 patients requiring subsequent suction bronchoscopy and no occurrence of tube blockage. Ninety-four percent of minitracheostomies performed were entirely uneventful. Bleeding was the most common complication (3.5%), and no instances of subglottic stenosis have occurred. During the review period, there was a significant increase in the percentage of patients requiring major operations undergoing prophylactic, but not therapeutic, minitracheostomy (p less than 0.001). This was associated with a significant decrease in the percentage of patients requiring suction bronchoscopy (p less than 0.001). We conclude that prophylactic minitracheostomy with the 20F pediatric silver tracheostomy tube is a safe and effective procedure in the prevention of postoperative sputum retention. PMID- 2596923 TI - Ultrasonic debridement of calcified pericardium in constrictive pericarditis. AB - Debridement of heavily calcified and adherent pericardium with an ultrasonic surgical aspiration device is described. The device proved to be a useful adjunct to the complete debridement of densely adherent pericardium. PMID- 2596924 TI - Tricuspid valve Candida endocarditis cured by valve-sparing debridement. AB - This report describes the case of a patient in whom Candida albicans tricuspid valve endocarditis was treated by excision of a large vegetation and partial tricuspid valvectomy without prosthetic valve replacement. In select patients, valve-sparing debridement may allow a long-term cure and may be the procedure of choice in the treatment of Candida tricuspid valve endocarditis. PMID- 2596925 TI - Total lymphoid irradiation in heart transplantation: adjunctive treatment for recurrent rejection. AB - In the face of recurrent heart transplant graft rejection refractory to all conventional immunotherapy, retransplantation is customary treatment. The case of a heart transplant recipient unsuitable for retransplantation whose recurrent rejection was successfully treated with postoperative total lymphoid irradiation is described. PMID- 2596926 TI - Carotid and aortic arch endarterectomy using hypothermic arrest with coronary bypass. AB - A 67-year-old man with symptomatic bilateral carotid artery obstructions and a large, friable atheromatous plaque of the transverse aortic arch required coronary artery bypass grafting for severe triple-vessel disease. An endarterectomy of the transverse arch and a left carotid endarterectomy were performed using deep hypothermic circulatory arrest concomitant with quadruple coronary artery bypass grafting. Recovery was uneventful. Hypothermic circulatory arrest provides adequate protection for this combined procedure and may eliminate cerebral embolization. PMID- 2596927 TI - The serratus sling: a simplified serratus-sparing technique. AB - A partial muscle-sparing technique is presented that combines the advantage of muscle sparing with the wide exposure offered by a posterolateral incision. The technique is simple and quick, does not require elaborate equipment, and facilitates thoracotomy closure. PMID- 2596928 TI - Improved visualization of the internal mammary artery with a new retractor system. AB - A new sternal retractor system was developed to improve exposure of the internal mammary artery and protect the lung. This retractor can be used for either single or bilateral dissection of the internal mammary artery. It has been used in more than 2,000 cases with excellent results. PMID- 2596929 TI - Left thoracotomy approach for coronary artery bypass grafting in patients with pericardial adhesions. AB - The left thoracotomy approach represents a safe alternative to median sternotomy for coronary artery bypass grafting in patients with pericardial adhesions. It provides an excellent exposure to the lateral aspect of the heart, and isolated circumflex coronary revascularization can advantageously be performed via this approach in select cases. PMID- 2596930 TI - Axillary artery insertion of an intraaortic balloon pump. AB - We describe a technique for insertion of an intraaortic balloon pump through the axillary artery. This approach is useful in patients requiring intraaortic balloon pump support before cardiac transplantation in that it dramatically increases patient mobility while awaiting a donor heart. PMID- 2596931 TI - Organ procurement for pulmonary transplantation. AB - Selection of suitable donors is critical to the success of clinical pulmonary transplantation. Requirements for lung donors, management before explantation, and methods of preservation were reviewed for the 70 heart-lung, eight double lung, and two single-lung transplantations performed at the University of Pittsburgh since 1982. Careful observation of trends of hyperoxygenation studies, chest roentgenograms, and Gram stain and culture results of tracheal secretions, as well as findings on bronchoscopy, can help identify which lungs not only have adequate function but are acceptable for transplantation. In spite of the rigid criteria used, 76% of tracheal cultures from donors deemed acceptable grew organisms. The presence of oropharyngeal flora has been shown to correlate with the development of early intrathoracic infections in the recipient. Prophylactic broad-spectrum antibiotic treatment of the donor is desirable to treat microbial contamination that could cause focal injury to the donor lung and predispose to infection in the recipient. Acceptance of less than ideal donors is ill-advised even though rejection of such donors conflicts with the current shortage of organs. PMID- 2596932 TI - Coronary-subclavian steal after coronary artery bypass grafting using the internal mammary artery. PMID- 2596933 TI - Autotransfusion of shed mediastinal blood. PMID- 2596934 TI - Impairment in right ventricular performance after left ventricular aneurysm operation. PMID- 2596935 TI - Retrotracheal mediastinal goiter with contralateral extension. PMID- 2596936 TI - Immediate treatment of severe hypertension. Widening the options. PMID- 2596937 TI - Loss of skepticism in medical education. PMID- 2596938 TI - How bad are diuretic-induced hypokalemia and hypercholesterolemia? PMID- 2596939 TI - Recommendations regarding public screening for measuring blood cholesterol. Summary of a National Heart, Lung, and Blood Institute workshop, October 1988. PMID- 2596941 TI - Recent sexual behaviors among homosexual men seeking primary medical care. AB - We studied the sociodemographic characteristics, knowledge, and beliefs about acquired immunodeficiency syndrome transmission and sexual practices of 823 gay or bisexual men seeking primary care. During the previous 2 months, 64% had engaged in at least one sexual behavior considered unsafe. These patients compared with those having safer sex, were younger, of lower socioeconomic status, and from a racial minority, especially Latino. The unsafe group also had more sexual partners, engaged in sexual acts more often, felt less in control over their sexual behavior, used recreational drugs more frequently, and were less likely to talk about safe sex with partners. The unsafe group had less adequate knowledge about human immunodeficiency virus transmission but felt safer from the risk of acquired immunodeficiency syndrome even when engaging in unsafe sex. Educational programs dealing more directly with belief systems and the potential addiction to recreational drugs and sexual behaviors need to be developed for primary care settings. PMID- 2596940 TI - Potassium restoration in hypertensive patients made hypokalemic by hydrochlorothiazide. AB - Among 447 hypertensive patients, most with a history of diuretic-induced hypokalemia, 252 developed diuretic-induced hypokalemia while receiving hydrochlorothiazide, 50 mg/d. In a randomized study we evaluated the efficacy of three drug regimens in restoring potassium levels while maintaining blood pressure control: hydrochlorothiazide (50 mg/d) plus potassium supplement (20 mmol/d); hydrochlorothiazide (50 mg/d) plus potassium supplement (40 mmol/d); or hydrochlorothiazide (50 mg/d) with triamterene (75 mg/d) in one combination tablet. In all groups, mean serum levels of potassium rose within 1 week and showed no further change thereafter. However, the hydrochlorothiazide/triamterene and hydrochlorothiazide plus 40 mmol of potassium regimens were significantly more effective in restoring serum potassium levels than was the hydrochlorothiazide plus 20 mmol of potassium regimen. A significant increase in magnesium levels was observed only in the group treated with the hydrochlorothiazide/triamterene combination. Each regimen provided continued control of mild to moderate hypertension. PMID- 2596942 TI - Hypokalemia after theophylline intoxication. The effects of acute vs chronic poisoning. AB - To characterize the frequency and pattern of hypokalemia (serum potassium level less than 3.5 mmol/L) after theophylline poisoning, we prospectively evaluated 88 consecutive patients with theophylline intoxication (serum theophylline concentration greater than or equal to 0.165 mmol/L). This mean admission serum theophylline concentration of this cohort was 0.331 mmol/L, with a range of 0.165 to 0.982 mmol/L. The simultaneous mean serum potassium concentration was 3.36 mmol/L (range, 2.20 to 5.80 mmol/L). Fifty-three patients (60%) were hypokalemic on hospital arrival. When, on the basis of recent ingestion, patients were separated into acute, chronic, or acute-on-chronic categories of theophylline intoxication, significant differences in serum potassium were found: Patients with acute theophylline intoxication had a mean serum potassium concentration of 2.94 mmol/L; 85% were hypokalemic. In contrast, patients with chronic theophylline intoxication had a mean serum potassium concentration of 3.83 mmol/L, with a 32% frequently of hypokalemia. These data demonstrate that hypokalemia is common after theophylline intoxication and has a significantly higher incidence after acute overdose. The difference in the frequency of hypokalemia between patients with acute vs chronic intoxication has unclear origins but may be related to the disparities in clinical course (particularly the appearance of seizures and cardiac arrhythmias) that have been observed after acute vs chronic theophylline intoxication. PMID- 2596943 TI - Diet vs exercise in weight maintenance. The effects of minimal intervention strategies on long-term outcomes in men. AB - The effect of a minimal intervention strategy on maintenance of weight lost through either energy restriction alone or exercise alone during the previous year was studied in a sample of middle-aged men. At the end of the initial year of weight loss, dieters (n = 44) and exercisers (n = 46) were randomly assigned to either an intervention condition, comprising monthly mailed informational packets and monthly to quarterly telephone contacts, or an assessment-only condition. The intervention had a significantly greater impact on weight maintenance in exercisers than it did in dieters. In addition, dieters showed a more variable pattern of weight gain and weight loss during the maintenance year than did exercisers. Based on 7-day food records and a 7-day physical activity recall questionnaire, exercisers reported a greater energy intake and a greater amount of time spent in vigorous activity relative to dieters at both the beginning and the end of the maintenance year. We conclude that exercise is easier to maintain in men using minimal contact strategies than dietary approaches to weight control focusing on modification of energy intake, with subsequent benefits in terms of both overall maintenance and stability of weight. PMID- 2596944 TI - Effects of meals and time of day on postural blood pressure responses in young and elderly subjects. AB - Previous data suggest that postural and postprandial hypotension are common in elderly subjects. This study evaluated the effect of age, meals, and time of day on supine and standing blood pressure (BP) and heart rate in healthy young and elderly subjects. A postural BP protocol was performed on 10 young and 16 elderly subjects during an overnight stay. The protocol included first morning and postprandial readings. The systolic and diastolic BP responses to standing were not significantly different between the two groups and were not affected by time of day. Postprandial recumbent BPs declined significantly only in the older subjects. There was no effect of meals on the BP response to standing. We conclude that healthy elderly subjects have a postprandial decline in BP even when supine. However, the BP response to standing is similar in young and elderly subjects and is not impaired by overnight rest or meals. This suggests that the regulation of BP after meals and with standing may be different. PMID- 2596945 TI - Successful treatment of resistant Paget's disease of bone with pamidronate. AB - Several agents are available for treatment of Paget's disease of bone, but their long-term use may be limited by resistance or adverse effects. I have treated two patients with exceptionally severe polyostotic Paget's disease (serum alkaline phosphatase values 25- to 30-fold above normal), in whom salmon calcitonin, sodium etidronate, and plicamycin each had become ineffective or could not be used. Pamidronate (3-amino-1-hydroxypropylidene-1,1-bisphosphonate) decreased serum alkaline phosphatase to normal or near-normal values and almost completely relieved symptoms, without recognizable adverse effects, except for transient mild hypocalcemia. The symptomatic and biochemical responses were maintained through 2 years of treatment and for more than 6 months after the treatment was discontinued. Thus, pamidronate can be very effective in severe, resistant cases of Paget's disease. Further study of this potent agent is needed to define the optimum regimen for maximum effectiveness and minimal long-term toxicity. PMID- 2596946 TI - [Iron status in presumably healthy children 10 months, 2 years and 4 years of age]. AB - Iron status was assessed using a combination of several biochemical indicators (serum ferritin, erythrocyte protoporphyrin, serum iron, MCV, hemoglobin) in 3,676 apparently healthy children. Children who were 10 months, 2 years and 4 years of age were selected from the population undergoing a free medical check up in a Paris Child Health Center. The prevalence of iron deficiency in children of parents from continental France was 29% in the 10 month olds, 13% in the 2 year olds and 7% in those who were 4 years of age. Corresponding figures in children born of immigrant parents were 50%, 44% and 15% respectively. Iron deficiency anemia was found in 8% of 10 month olds from continental France versus 23% in the other group. Children born of parents from the South Sahara were found to be at high risk for iron deficiency. PMID- 2596947 TI - [Iron deficiency and psychomotor development tests. Longitudinal study between 10 months and 4 years of age]. AB - A longitudinal study of iron deficiency and of psychomotor development was carried out in 147 children followed between the ages of 10 months and 4 years in 2 well-baby out-patient clinics in Paris area. The tests used were those of Brunet-Lezine. The frequency of iron deficiency anemia was 22% at age 10 months, 9% at 2 years and 2% at 4 years. Ferritin blood levels were abnormally low in 35% of patients at 10 months of age, in 36% at 2 years and in 40% at 4 years. No significant correlation could be found between the Development Quotient (DQ) and biological data at the ages of 10 months and 4 years. On the other hand, at age 2, the mean DQ values were higher in children without deficiency than in those with deficiency with respect to the following biological parameters: hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin concentration. These differences persisted even after taking into account variables known to influence psychomotor development. PMID- 2596948 TI - [Anderson's disease. Clinical and morphologic study of 7 cases]. AB - Anderson's disease is a rare autosomic recessive condition involving the transport of fat through the intestinal mucosa, which could be due to a defect in the intestinal form (B48) of apolipoprotein B. Isolated cases and one important series only have been reported. We wish here to complete the description of the disease. Seven children (age 6 months to 13 years at time of diagnosis) were followed for one month to 15 years. They presented with a malabsorption syndrome, malnutrition, fatty diarrhea (steatorrhea 4-18 g/24 h), failure to thrive (height -1 to -5.5 SD for age) and sometimes disappearance of deep tendon reflexes. Biologically they had signs of malabsorption, hypocalciuria, osteoporosis, low serum iron, decreased levels of vitamins A and E, and hypo-alpha- (50-127 mg/100 ml) and beta- (73-175 mg/100 ml) lipoproteinemia due to decreased levels of plasma cholesterol (40-70 mg/100 ml), and phospholipids (34-67 mg/100 ml); apolipoproteins A1 (26-69 mg/100 ml and B (21-44 mg/100 ml) were also low. After a fatty meal, triglycerides and apolipoproteins did not increase and chylomicrons did not appear. Jejunal biopsies showed the characteristic aspect of enterocytes loaded with lipid droplets. On electron microscopy, these fat droplets were seen in the cytoplasm but neither in the endoplasmic reticulum and the Golgi complex nor in the intercellular spaces. They did not appear to be enclosed in membranes and differed from chylomicrons by their size and density. The disease could thus be due to an abnormal apolipoprotein B48, which would prevent its binding to triglycerides and thus the formation of chylomicrons. PMID- 2596949 TI - [Infection by the HIV virus and transfusions. Study of 38 pediatric cases]. AB - We report the cases of 38 children with transfusion-associated HIV infection: 18 hemophiliacs and 2 patients with Von Willebrand disease, 6 with hemoglobinopathies, 8 with malignant diseases or aplastic anemia, 2 transfused during neonatal period and 2 during a surgical operation. Two groups with a different prognosis were found: In group A [hemophilia and Von Willebrand disease (n = 20)] 17 patients were asymptomatic or only with lymphadenopathy; 3 reached stage IV and none died. In group B [Others (n = 14)] 2 patients were asymptomatic, 4 reached stage IV and 8 died, 4 of them directly from AIDS. The difference between both groups was statistically significant. Prognosis of HIV infection is particularly severe in patients with leukemia, malignant tumors and aplastic anemia. PMID- 2596950 TI - [Problems stemming from pregnancy in a woman with phenylketonuria]. AB - A normal infant was born to a 25 year-old mother with phenylketonuria who had never been treated. The mother had been fed a phenylalanine restricted diet for 3 months before the beginning of the pregnancy. Dietary control was maintained throughout the whole gestation. The problems of dietary control in a mentally retarded woman are analysed. PMID- 2596951 TI - [Primary severe neonatal hyperparathyroidism. Significance of genetic study and emergency parathyroidectomy]. AB - Primary hyperparathyroidism in the newborn is uncommon. The clinical features as well as histological lesions of the parathyroid glands are quite different from those in the adult. The degree of hypercalcemia and the high frequency of pulmonary complications may threaten the life of the infant. Management is straight forward: early surgical removal and supplementation with calcium and vitamins should be quickly followed by an autograft. In the severe case herein reported, the diagnosis, suggested by family history, was confirmed by a rapid increase in calcemia as well as by very characteristic skeletal lesions. PMID- 2596952 TI - [Protection of children from automatic garage doors]. PMID- 2596953 TI - [Blood concentrations of amoxicillin after 4 orally administered doses of 25 mg/kg/day in newborn infants]. PMID- 2596954 TI - [Microbial mutagenicity testing of N-nitrosoiminostilbene and N nitrosoiminodibenzyl, the nitrosation products of the drugs carbamazepine and trimipramine hydrochloride]. AB - The active agents of the drugs Finlepsin and Herphonal, carbamazepine and trimipramine, were nitrosated under simulated human gastric conditions. For both formed N-nitroso compounds, N-nitroso iminostilbene (N-nitroso-5H dibenz(b,f)azepine) and N-nitroso iminodibenzyl (N-nitroso-10,11-dihydro-5H dibenz(b,f)azepine), tests for mutagenic potency in the Ames-test gave negative results. PMID- 2596955 TI - Non-random karyotypic changes in Djungarian hamster tumors induced by 3 methylcholanthrene. AB - The karyotypes of 30 tumors (sarcomas and adenocarcinomas) induced with methylcholanthrene in Djungarian hamsters (Phodopus sungorus campbelli) have been investigated. In 23 tumors structural changes of the short arm of X-chromosome (Xp+ or Xp = type) were revealed. Non-random rearrangements of 3p, 7q and 8q were also observed. Other structural or numerical changes of the karyotype were accidential. For majority of tumors the presence of chromosome markers with long homogeneously staining regions or double minutes, structures are known as cytological manifestation of gene amplification, was typical. Induced tumors of the Djungarian hamster might serve as an interesting tool for studies of relationship of somatic cell genetic changes to different aspects of chemical carcinogenesis. PMID- 2596956 TI - [Experiments on the modification of the distribution of the activity of various alpha-L-arabinofuranosidases following i.v. application in tumor-bearing mice]. AB - Graffi et al. have proposed the use of exogenous enzymes for selective cleavage of inactive transport forms of cancerostatic substances in tumor tissue. Enzymes appropriate for this purpose should, if possible, show also a certain enrichment in the tumor tissue. In studies on the pH-labile alpha-L-arabinofuranosidase from G. myabena in tumor-bearing mice, under defined conditions in the tumors there could be demonstrated a higher concentration of the active form of the enzyme than in most of the normal tissues. However, the enzyme activity is eliminated from the organism in a relatively short time through excretion and inactivation. The application of glucose led to a strong increase of activity of the enzyme injected, both in the tumors and in the normal tissues. It has been shown in the present investigations that this increase in the enzyme activity can be curtailed more strongly in normal tissue by alkali application than in the tumors. In this way, a distribution of the enzyme activity favorable for therapy experiments is obtained. Only in the kidney and urine has a higher activity of the applied enzyme been measured than in the tumors. In the second part of this work it has been attempted to achieve accumulation of activity of the pH-stable alpha-L arabinofuranosidase from A. niger through application of angiotensin, but no positive results have been reached under the various experimental conditions used. PMID- 2596957 TI - Gas chromatographic-mass spectrometric investigation of four commercial pristane (2.6.10.14-tetramethylpentadecane) preparations used for plasmacytoma induction in BALB/c mice. AB - The most widely studied model of plasmacytomagenesis is the induction of plasmacytomas by intraperitoneal injections of pure alkanes such as pristane (2.6.10.14-tetramethylpentadecane). The presence of small amounts of genotoxic contaminants, that could contribute to the complex oncogenic process, in commercial pristane preparations has not been completely ruled out. Therefore, we conducted a chemical analysis of different pristane preparations applying a combined GC/MS technique, but were not capable of identifying any obvious or putative genotoxic/cancerogenic contaminants. PMID- 2596958 TI - Induction of thyroid neoplasms in the rat. A histochemical, immunohistochemical, autoradiographic and ultrastructural study. AB - Papillary carcinomas of the thyroid gland induced in rats by combined methylthiouracil (MTU)/nitrosomethylurea treatment were studied electron microscopically and histochemically for their acid phosphatase activity, radioactive iodine uptake and for their thyroglobulin synthesis. The papillary carcinomas accumulated radioactive iodine, synthesized thyroglobulin and showed a perinuclear localization of acid phosphatase activity in the cytoplasm. After omitting the reactive thyrotropic effect (cessation of MTU administration) a decrease of both iodine organification and acid phosphatase activity was observed. The synthesis of thyroglobulin was also reduced. The changes in the ultrastructure of tumour cells corresponded to the respective functional activities. The results suggest that the papillary carcinomas may have a functional dependence on thyroid-stimulating hormone. PMID- 2596959 TI - [Results of antineoplastic chemotherapy based on the oncobiogram]. AB - An organ culture assay for in vitro chemosensitivity testing was used to predict clinical responses of various tumors to antineoplastic chemotherapy. 9 patients with advanced mammary carcinomas, 7 patients with metastatic malignant melanomas, 1 patient with advanced ovarian cancer, 1 with bronchogenic carcinoma, 1 with metastatic leiomyosarcoma and 1 patient with a metastatic carcinoma of the sweat gland were included in the study. 20 in vitro-in vivo correlations were evaluable. 5/9 of the mammary carcinomas showed an objective response, 0/7 malignant melanomas were sensitive in vivo. Further investigations have to assess the value of chemosensitivity assays to predict clinical response for patients with solid tumors. PMID- 2596961 TI - Cancer care in Greece. PMID- 2596960 TI - [The importance of prognostic factors in malignant melanoma of the skin]. AB - 122 primary malignant melanomas of the skin were investigated to estimate the histologically and clinical criteria of melanoma for the prognostic evaluation of the disease. As result the tumor thickness (Breslow) in mm is the best prognostic value. The prognostic index allows an assay to determine the risk of metastases. On this basis it is possible to distinguish between melanomas with high and low risk of metastases. This is important as a criteria for the determination for the adjuvant treatment. PMID- 2596962 TI - Head injury outcome up to ten years later. AB - Head injury outcome was studied in 63 severe traumatic brain-injured (TBI) victims up to ten years after injury. Extent of improvement and residual deficits in physical and mental impairment and mood and frustration tolerance changes are reported. The impact of these changes upon ability to work and to establish living situations is presented. It was found that long-term outcome is related significantly both to elapsed time between injury and admission to an intensive rehabilitation hospital program and to level of disability at admission. Major problems and needs at follow-up are reported. Thirteen demographic and clinical profile parameters are suggested to permit meaningful comparisons of long-term outcome among different groups of TBI victims. PMID- 2596963 TI - Vestibular stimulation after head injury: effect on reaction times and motor speech parameters. AB - Earlier studies by other authors indicate that vestibular stimulation may improve attention and dysarthria in head injured patients. In the present study of five severely head injured patients and five controls, the effect of vestibular stimulation on reaction times (reflecting attention) and some motor speech parameters (reflecting dysarthria) was investigated. After eight weeks with regular stimulation, it was concluded that reaction time changes were individual and consistent for a given subject. Only occasionally were they shortened after stimulation. However, reaction time was lengthened in three cases, prohibiting further stimulation in one case. Motion sickness was prohibitive in a second case. However, after-stimulation increase of phonation time and/or vital capacity was found in one patient and four controls. Oral diadochokinetic rates were slowed in several cases. Collectively, when stimulation induced changes of reaction times or motor speech parameters, the changes were more pronounced in patients than in controls. PMID- 2596965 TI - Intertester reliability of the hand-held dynamometer for wrist flexion and extension. AB - This study was conducted to determine the intertester reliability of a hand-held dynamometer for the wrist flexor and extensor muscles. Using the break test on 20 healthy subjects, three testers obtained two measures of strength for each muscle group. The data were analyzed using the Pearson product-moment correlation coefficients, intraclass correlations, and an analysis of variance (ANOVA) for repeated measures. Our Pearson product-moment correlations ranged from 0.89 to 0.95 for the intertester reliability of the wrist extensors and 0.90 to 0.93 for the wrist flexors, whereas the intraclass coefficients were 0.91 and 0.85, respectively. Although these correlations were high, ANOVA tests revealed that significant differences existed between testers for both the wrist flexion and extension data (p less than .05). From these results we concluded that although the correlations between testers were good, ANOVA tests suggested that there was limited reliability between testers. PMID- 2596964 TI - Rehabilitation inpatient screening of early cognitive recovery. AB - A neuropsychologic bedside screening instrument has been developed for use with recovering, cognitively impaired inpatients. Its purpose is to help clarify the nature and extent of cognitive impairments and to quantify change during recovery. The Barry Rehabilitation Inpatient Screening of Cognition (BRISC) represents an extension downward into the broad range of below-normal functioning. Reliability and validity data, based on 20 head-injured inpatients, and normative data, based on 52 nonpatients are presented. These data indicate that the BRISC is an appropriate instrument for use with its target population. PMID- 2596966 TI - Sauna to transiently improve pulmonary function in patients with obstructive lung disease. AB - The influence of sauna on pulmonary functioning in patients with an obstructive pulmonary disease was studied in 12 male patients by measuring forced vital capacity (FVC) and forced expiratory volume in one second on seven measure points the day of the sauna program. Despite the fact that body cooling and changes in osmolality of bronchial liquid can induce bronchoconstriction, we measured a significant improvement of the lung function parameters: FVC values were 3.22 +/- 0.89 and 3.6 +/- 0.99 before and after the sauna program, respectively. It is concluded that patients with an obstructive pulmonary disease can take part in sauna programs without eliciting bronchoconstriction; sauna even causes transient improvement of the lung function. PMID- 2596967 TI - Neurologic sequelae of minor electric burns. AB - Although neurologic pathology is a well-documented sequela of major electric burns, there are few reports of complications arising from less extensive electrically induced trauma. Two cases of patients with significant disease subsequent to minor electric burns are presented. In one patient with a 2% superficial partial-thickness burn of the right forearm, nerve conduction studies, electromyography, and somatosensory evoked potential studies were consistent with right median mononeuropathy at the wrist and a distal slowing of the right ulnar nerve. The second patient presented with persistent numbness, hyperpathia, and burning in his left hand after an electric shock in a telephone booth. He had a creatine phosphokinase of 2000m mu/mL but no surface burn. A left stellate ganglion block provided complete resolution of his symptoms and established a diagnosis of minor reflex sympathetic dystrophy. PMID- 2596968 TI - Double disability of hemiplegia and hip disarticulation: rehabilitation outcome. AB - Double disability of hemiplegia and hip disarticulation is uncommon. To our knowledge, there are no reports of such patients and their rehabilitation outcomes. We report on a patient with hemiplegia and hip disarticulation who became independent in prosthetic ambulation and activities of daily living. Motivation, age, good neuromuscular status, and past successful prosthetic use favored the excellent rehabilitation outcome in this patient. PMID- 2596969 TI - Prosthetic feet. PMID- 2596970 TI - Shoulder abduction relief sign. PMID- 2596971 TI - Electrically-induced exercise. PMID- 2596972 TI - A comparative study of entry modes into C6/36 cells by Semliki Forest and Japanese encephalitis viruses. AB - The entry modes of Semliki Forest virus and Japanese encephalitis virus into C6/36 cells were compared by electron microscopic observation. At physiological pH, the two viruses showed characteristically different entry modes. Following attachment to the plasma membrane, many SF virions appeared within plasma membrane invaginations and cytoplasmic vesicles; on the other hand, JE virions remained to be found exclusively at the cell surface, with no virions appearing within cytoplasmic vesicles. Electron microscopic observation, therefore, indicated that SF virus entered C6/36 cells by receptor-mediated endocytosis, while JE virus penetrated the cells at the surface and disintegrated at or near the adsorption sites. At pH 5.8, SF virus also entered C6/36 cells by direct penetration at the cell surface. On the basis of the present and other findings, the following working hypotheses are presented for future investigations: (a) at physiological pH, the fusion protein of SF virus is in an inactive state and needs to be activated by acidic pH within the endosome in order to act on the host-cell membrane, but that of JE virus is in an active state and is capable of dissolving the host plasma membrane at the cell surface immediately after the attachment; (b) the states of viral fusion proteins (inactive or active) at the time of viral attachment to the cell surface determine which of the two entry modes these viruses follow. PMID- 2596973 TI - Molecular cloning of the Rauscher murine leukemia virus. Disease spectrum and integration pattern. AB - After transfection of NIH 3T3 cells with DNA from molecularly cloned Rauscher MuLV, virus was isolated which showed a disease spectrum comparable to that of R MuLV cloned biologically by endpoint dilution. In both cases sites of proviral integration vary from 2-5 per leukemic tissue and occur apparently at random. PMID- 2596974 TI - Temperature dependent replication of porcine parvovirus isolates. AB - The replication of four porcine parvovirus isolates, NADL-8, NADL-2, KBSH, and Kresse, in swine testes cells were compared at temperatures of 32, 37, and 39 degrees C. Replication of the Kresse isolate was restricted at 32 and 37 degrees C as evidenced by progeny virus, virus polypeptide and viral DNA synthesis, but not at 39 degrees C. In contrast, replication of KBSH was restricted at 39 degrees C, but not at 37 or 32 degrees C. Findings from this study support the contention that replication of KBSH and Kresse isolates are temperature dependent. PMID- 2596975 TI - Feline calicivirus protein synthesis investigated by western blotting. AB - We have used Western blotting to examine the accumulation of feline calicivirus proteins within the infected cell. Experiments using elevated growth temperature to block post-translational cleavage have demonstrated two additional high molecular weight protein bands 125 kd and 123 kd respectively which may be precursor polyproteins. Inhibition of proteolytic processing with p fluorophenylalanine led to the accumulation of several additional protein species which may represent intermediates in the protein processing pathway. None of these proteins were related to the 62 kd major capsid protein (cP62) of the virus as judged by reaction with monoclonal antibodies. The production of a 76 kd capsid precursor protein (cpP 76) was demonstrated for the first time in FCV infected cells. The pathway by which calicivirus polypeptides are made thus appears highly complex and may involve temporal regulation of protein synthesis as well as protein processing. Tentative identification of primary, intermediate and mature forms of virus proteins is discussed. PMID- 2596976 TI - Neutral red-labeled influenza virus loses photosensitivity during absorption to host cells but not to erythrocytes. AB - Neutral red (NR)-labeled influenza virus is extremely photosensitive. Unlike NR labeled picornaviruses which lose their photosensitivity only after penetrating the host cell, NR-labeled influenza virus loses most of its photosensitivity during adsorption at 4 degrees C. We demonstrate that the underlying reaction occurs within seconds of adsorption and that it is irreversible, i.e., NR virus eluted from chick embryo cells after adsorption is hardly photosensitive anymore. In contrast to this, NR virus adsorbed to and eluted from erythrocytes retains its original photosensitivity. We suggest that the loss of photosensitivity during adsorption of NR virus to host cells reflects a conformational change in the virion which is not elicited by adsorption to red blood cells. PMID- 2596977 TI - [A histochemical study of enzyme activity in the myocardium of victims of sudden death with small-focal cardiosclerosis]. AB - On the material of early autopsies of the above patients the activity of the following myocardial enzymes was undergone the quantitative histochemical study: succinate, lactate, (beta-oxybutyrate, d-glycerophosphate, glucose 6-phosphate and alcohol dehydrogenase, NAD-diaphorase, catalase, phosphorylase. The increase of the activity of practically all enzymes studied was observed in the myocardial areas with no circulation disturbances. This increase was due to the moderate myocardial hypertrophy. On the contrary, in the areas with a non-even blood supply (ischemia) the decrease of the activity of all oxidative-reductive enzymes was observed. The presence of such foci in the myocardium which occur in 70% cases studied facilitates the development of the ventricular fibrillation with a fatal outcome. The enzyme depression is particularly pronounced against the background of a high alcoholic content. PMID- 2596979 TI - [Ultrastructure of the peri-infarction zone during treatment of experimental myocardial infarct with cardiolin]. AB - Cardiolin therapy influence on the periinfarction zone cardiomyocyte ultrastructure, sarcolemma permeability for colloidal lantan, myocardium energy level were studied in 25 white noninbred rats with experimental myocardial infarction. 6 hours after coronary occlusion ultrastructural damage in treated rats was less pronounced and mitochondria energy efficiency ratio was higher than those in the control group. 24 hours after the occlusion the tendency to normalization of the cardiomyocyte damage in treated rat myocardium was demonstrated, while in non-treated animals ischemic damage becomes irreversible, this being confirmed by the test with colloidal lantan. Cardiolin therapy prevents the infarction zone expansion by decreasing ischemic damage of periinfarction cardiomyocytes and by stimulating regeneration processes in these cells. PMID- 2596978 TI - [Structural analysis of the interaction of low density lipoproteins with arterial intima cells in atherosclerosis]. AB - Structural characteristics of low density lipoprotein (LDL)-intimal cellular element interaction were studied in atherosclerotic lesions in the aortas obtained from rabbit with experimentally induced hypercholesterolemia and in human coronary arteries. An electron microscopic autoradiographic examination using 125I to study the in vivo interaction between LDL and rabbit aortic intimal cells indicated that the formation of foam cells was associated with activated endocyte activity and uncontrolled capture of atherogenic lipoproteins. The structural analysis of the interaction of native and modified LDL labelled with colloid gold, on the one hand, and human coronary intimal cells, on the other, was made by using ultrathin sections. This enabled the localization of the receptors to lipoproteins to be established. This also demonstrated that transformation of the cells to foam ones was due to the functional insufficiency of lysosomal activity and to the filling of the cytoplasm with membranelles and membrane-surrounded lipid vacuoles. PMID- 2596980 TI - [A quantitative analysis of regional features in the structure of aortal endothelial cells in short-term hypertension]. AB - The results of quantitative analysis of regional differences in the structure of thoracic aorta endotheliocytes in normal and hypertensive rats are presented. Scanning electron microscopy and semiautomatic image analyser were employed in studying the cellular structure in three regions of aorta endothelial layer: dorsal and ventral surfaces and region of the intercostal arterial ostia. The data obtained show that in cases of a short-duration hypertension the most pronounced are the alterations in endotheliocytes of the dorsal surface. Thus, the results confirm the heterogeneity of the aortic endothelium under normal conditions and demonstrate that differences in overlapping of neighbouring endotheliocytes is the cause of the observed alterations in cases of hypertension. PMID- 2596981 TI - [Features of senile cerebral amyloidosis]. AB - It is established, on the basis of the autopsy material of I. M. Sechenov First Moscow Medical Institute for 1983-1987 (517 patients who died at the age of 40-89 years), that senile cerebral amyloidosis (SCA) is a local form of senile amyloidosis which occurs in 4.4% persons over 60 years of age. At the autopsy SCA is revealed in 21.4% cases, but the examination of the brain for amyloid increases the percent up to 78.6. Amyloid deposits are observed as senile plaques in the vessels of pia mater, plexus chorioideus and intracerebral vessels. Genetic factors in the SCA development can not be excluded. PMID- 2596982 TI - [Morphology and pathogenesis of changes in the lungs during drug-induced anaphylactic shock in humans]. AB - The paper presents the results from examinations of morphological changes in the lung of 51 persons who died from drug-induced anaphylactic shock at the age of 6 months to 67 years. The patients died several minutes to 7-10 days following drug administration. The causes of the shock were administrations of antibiotics, novocain (procaine hydrochloride), glucose, radiopaque agents, plasma substituting solutions, protein hydrolysates, and other substances. Forty-nine persons died after parenteral drug administration. The most frequent concurrent conditions were gastrointestinal and respiratory diseases and pregnancy. A clinical and morphological analysis of the material enabled the authors to single out 6 types of drug-induced anaphylactic shock: asphyxial, bronchospasmic, hemodynamic, cerebral, abdominal and a variant with prevalent pulmonary edema. Typical characteristics of pulmonary alterations are described in each type of the shock. PMID- 2596983 TI - [Intralobar sequestration of the lungs]. AB - The paper deals with 6 cases of intralobar pulmonary sequestration that is a rare developmental defect accompanied by other anomalies and tumors. In 4 cases, the diagnosis was made on the basis of X-ray and bronchologic examinations before surgery, in 2 cases, during the surgery. The morphologic features were found to be cystic formations accompanied by chronic inflammation in the lung tissue, cylindrical brochiectasis along with celomic cyst of the pericardium and microcarcinoid in the cyst wall. PMID- 2596984 TI - [Morphology of erythroblastic bone marrow islands in hematologic patients]. AB - Erythroblastic islands (EI) available for light-microscopic study were obtained from 25 patients with a haemopoiesis pathology from the ileum bone using the method suggested by the authors. Erythropoiesis activation in the osteomyelofibrosis in the erythremic stage, erythremia and haemolytic anemia was followed by the appearance in the "crown" of the central macrophage from 34 to 37 nucleated erythroid cells, enhanced phagocytosis of the normoblast nuclei and the presence of 2-4 nucleoli in the macrophage and proerythroblast nuclei. PMID- 2596985 TI - [Myocardial hypoplasia of the right heart ventricle (Uhl's anomaly)]. AB - Uhl's anomaly (right ventricular myocardial hypoplasia), a rarely occurring congenital anomaly of the heart, is described in a newborn who lived 69 hours. In this case, the above anomaly was accompanied by an open oval window and atresia of the pulmonary artery, which led to the baby's short-term lifespan. PMID- 2596986 TI - [A case of lepromatous leprosy]. AB - The paper describes a case of lepromatous lepra diagnosed from the skin biopsy specimen taken in a 23-year-old male patient. It provides histologic signs that are beneficial for correct diagnosis. Emphasis is placed upon the necessity for staining by the Ziehl-Neelsen method to detect microorganisms in infiltrative and granulomatous skin lesions. PMID- 2596987 TI - [Pseudomyxoma of a retrocecally-positioned appendix with growth into the retroperitoneal space and with exterior fistulae]. AB - One observation of the above tumor complicated by the development of the external fistulas is described. PMID- 2596988 TI - [Idiopathic calcification of the cerebral vessels (Fara's syndrome) in conjunction with pregnancy]. AB - Typical Fara's syndrome occurs rarely, particularly in combination with pregnancy. It is characterized by the deposits of calcium, magnesium, zinc and manganese salts in the medium layer of the brain vessels. The salts are arranged in a concentric pattern thus giving the arteries of the middle diameter and arterioles the appearance of a narrow tube. The capillaries are transformed into the salt lumps with the obliterated lumen. Etiology and pathogenesis of the disease remain unclear. PMID- 2596989 TI - [Vascular malformation of the spinal cord]. AB - A case of the arteriovenous aneurysm is described. This congenital anomaly occurs rarely in all parts of the central nervous system including the spinal cord. The aneurysm damages the spinal cord due to haemodynamic and haemorrhagic complications, inflammation and compression resulting in the neuron death and the disturbance of the spinal cord functions. PMID- 2596990 TI - [The Commission against smoking of the Brazilian Medical Association. Presented at the 2d National Symposium on Smoking Control (Sao Paulo--23 November 1987)]. PMID- 2596991 TI - [Impressions of an international congress of cardiology: current trends in research]. PMID- 2596992 TI - [Comparison of histologic changes in Chagas' cardiomyopathy and dilated cardiomyopathy]. AB - In this study the histopathologic features of Chagas' disease and idiopathic dilated cardiomyopathy were compared in 38 patients with congestive heart failure, classes II or III. Biopsy specimens were obtained with the Stanford model needle for right ventricle. Twenty-two patients presented non-chagasic dilated cardiomyopathy, and 16 were carriers of Chagas' disease. Twenty-three were male and 15 were female; their ages varied 18 and 49 years (mean 35.5). Fibrosis was slightly more frequently and intense in Chagas' disease than in dilated cardiomyopathy. Myocarditis aspect also was more frequent in Chagas' disease than in dilated cardiomyopathy (62.4% vs. 50%), with all cases showing a chronic form; acute myocarditis was observed only in dilated myocardiopathy. These differences, however, did not reach statistical significance. In conclusion, the presence of fibrosis, hypertrophy and moderate to severe degrees of chronic inflammatory infiltrate are suggestive of but not pathognomonic of Chagas' disease. On the other hand, dilated myocardiopathies are more frequently associated with less fibrosis or hypertrophy and the presence of mild degree of inflammatory infiltrate. The arrangement of this inflammatory infiltrate tends to be diffuse in dilated cardiomyopathy and in chagasic myocarditis it is multifocal, very similar to the histopathological aspect found in myocardial rejections episodes of transplanted hearts. PMID- 2596993 TI - [Pulmonary hypertension: a serious complication in the postoperative period of tetralogy of Fallot]. AB - Among 1,142 patients who underwent total correction of tetralogy of Fallot from May of 1960 to december of 1986, five (0.43%) presented refractory cardiac failure. Pre and postoperative control was based on symptoms and clinical signals, electrocardiogram, conventional radiographies, cardiac catheterism, cineangiocardiography, and necropsy in one case. The evolution in immediate and late postoperative periods were not good. One patient deceased in the first day after surgery: the others had complications as severe pulmonary insufficiency, diffuse and severe hypocontractibility of the right ventricle, with three late decreases. Only one patient is alive, with congestive cardiac failure hardly controllable. PMID- 2596994 TI - [Intraerythrocytic potassium and diuretic therapy]. AB - Diuretic-induced hypokalemia is one of the most common and important disturbances during antihypertensive therapy. However, it has been suggested that determination of serum potassium levels may not reflect significant changes of its intracellular concentration. This study was performed to evaluate whether there is any change of red cell potassium concentration as compared to serum potassium levels, in ten patients receiving chlorthalidone, 25 mg/day, during 4 weeks. Significant antihypertensive effect was achieved and despite serum potassium levels less than 3.5 mEq/1 occurred in four patients, no significant change in intracellular concentration of potassium was observed in this population with essential hypertension. PMID- 2596995 TI - [Ischemic cardiopathy with normal epicardial coronary arteries. Probable spasm of the coronary arteries. A case report]. AB - The authors discuss the case of a young woman, with chest pain at rest and normal coronary arteries. Sixty-three days after the onset of the symptoms the patient had a myocardial infarction. The coronariogram showed obstruction of the left coronary artery in its full length. The authors consider that a coronary spasm was the cause of the infarction. It is very likely that independent of personal characteristics, coronary spasm may be persistent, involve the whole extent of the vessel and occur even with use of vasodilator drugs. PMID- 2596996 TI - [Mitral valvuloplasty with balloon catheterization in pregnant patients. Report of 3 cases]. AB - The authors report on three pregnant patients with mitral stenosis with heart failure in functional class IV (NYHA) unresponsive to clinical treatment. They were submitted to mitral valvuloplasty, with significant clinical improvement, and were, hence, asymptomatic. Despite the small number of cases, it may be concluded that the procedure is simple and safe, which can be attested by the successful results. PMID- 2596997 TI - [The effects of antihypertensive therapy on the quality of life]. PMID- 2596998 TI - [Apical left ventricular involvement in chronic Chagas' cardiopathy: clinical and ventriculographic aspects]. AB - The present study comprises 62 patients with Chronic Chagas' Heart Disease. In addition to clinical examination, serologic, roentgenologic, hemodynamic, electrocardiographic, left cineventriculographic and cinecoronariographic studies were performed, with subsequent evaluation apical left ventricule. Thirty two patients were women and 30 were men, varying between 21 and 64 years of age, all with positive serological tests, all with cardiovascular symptoms, 26 with myocardial failure (11 with left ventricular failure and 15 with congestive heart failure), heart size was normal on X-ray in 37 patients with cardiomegaly in 25 (slight in 10; moderate in 8 and accentuate in 7). The electrocardiogram revealed in 41 instance of conduction defects. The left ventriculogram showed an apical lesion in 52 patients (83.87%) with: localized hypokicinetic in 4 (6.45%), diffuse hypokicinetic in 6 (9.68%) and, apical lesion in 48 (77.42%). The shaped apical lesion as a nipple in 17 (27.42%), as finger in 17 (27.42%), and half-moon in 14 (22.18%). The apical lesion was observed in 20 of 26 patients with myocardial failure (76.92%). In 9 patients was associated with others aneurysms. In 3 patients apical thrombus was detected. PMID- 2596999 TI - [The importance of mitral calcification in the elderly]. AB - The echocardiographic study of 480 patients over 60 years (medium age: 75.4) revealed 37 (33 women) of them having mitral calcification (MC). The analysis of clinical and metabolic data of these 37 patients plus their electro, phono and echocardiographic assessment revealed: 1) MC was observed in 7.7% of this elderly population and its incidence tended to increase with age; 2) MC was more frequent and more pronounced in women; 3) cardiocirculatory abnormalities responsible for a high systolic pressure in the left ventricle, such as hypertension (64.9%) and aortic stenosis (10.8%) were the most commonly associated cardiac pathologies; 4) no history of illnesses usually aggressive to the mitral valve was detected; 5) plasma lipids and calcium were normal; 6) in 27.0% of patients with MC there was some degree of mitral stenosis and/or insufficiency and surgical correction has been considered in some cases; 7) changes in production and/or conduction properties were frequent, causing bradyarrhythmias, tachyarrhythmias and intraventricular block. Taking these points into consideration, a careful follow up of confirmed cases is suggested, in order to detect and treat any complications without delay. PMID- 2597000 TI - [Heparinization control by activated coagulation time in cardiac surgery with extracorporeal circulation]. AB - The authors studied 20 patients undergoing cardiac surgery with extracorporeal circulation using a protocol proposed by Bull for the control of heparinization using the activated coagulation time of whole blood proposed by Hattersley. The patients, alterations in the coagulation and in red cell values were evaluated comparing the pre-operatory values with the post-operatory ones. The activated coagulation time (ACT) was evaluated as to its variability in different periods (pre, trans, and post-surgery). All the results were compared with world literature. They conclude that it is an excellent method for the control of the monitoring of heparin therapy and neutralization with protamine sulfate, which was used in lower doses than those referred to in literature. No post-operatory complications due to alterations in the coagulation system were observed. The total doses of heparin and protamine per kilogram were, respectively, 5.85 mg and 4.34 mg. There was significant variation between the erythrocytes, the hemoglobin and the platelets (p less than 0.001). As to the prothrombin time, the partial thromboplastin time, the coagulation time and the fibrinogen, none showed significant variation. The ACT did not show significant variation between the values obtained during perfusion, and neither between the basal value and the value post-protamine, the basal and the 30 minutes post-protamine, and the post protamine and 30 minutes post-protamine. PMID- 2597001 TI - [Unstable angina, Prinzmetal's variant and transient Q waves. Report of a case]. AB - A case is reported of the variant form of Prinzmetal angina, occurring two months after effort angina, in which the electrocardiogram revealed a Q wave in V2 in addition to ST segment elevation in precordial leads all of which disappeared in a few minutes. Several hours later, the ECG changes were suggestive of antero septal infarction. However, four days later an R wave was present in lead V2, and 12 days after the acute episode, the tracing became entirely normal. Cinecoronary angiography revealed severe obstruction of the anterior descending artery, and a moderate obstruction of the left circumflex artery. The possibilities of spasm and/or coronary thrombosis, of spontaneous recanalization and of reperfusion due to thrombolysis are discussed, in addition to interpreting the abnormal Q waves as presumably due to severe myocardial ischemia resulting from acute coronary insufficiency. The present case exemplifies the concept that the syndromes of acute coronary heart disease cannot always be precisely differentiated, since they often overlap and are difficult to identify. PMID- 2597002 TI - [Acute pulmonary edema secondary to pheochromocytoma. A case report]. AB - Authors report a case of a patient with abdominal pheochromocytoma who presented recurrent episodes of acute pulmonary edema. No cardiopathy was detected either by clinical examination or by electrocardiogram, echograms or invasive cineventricleangiograma. They concluded that a non cardiogenic etiology is possible for the referred clinical manifestations. PMID- 2597003 TI - [Tetralogy of Fallot associated with total anomalous drainage of the pulmonary veins. Report of 2 cases]. AB - The authors report on two cases of tetralogy of Fallot (TF) associated with total anomalous pulmonary venous return to the coronary sinus. The clinical manifestations in both children were the same as of classical TF and diagnosis was confirmed by cineangiography. The patients underwent total surgical correction and the first one died in the immediate post-operative period. The second patient had an uneventful recovery. The rarity of this association is the main reason of this report where clinical and surgical findings are discussed. PMID- 2597004 TI - [Surgical approach in bacterial endocarditis of the tricuspid valve in children. Report of 2 cases]. AB - The two techniques usually employed for the surgical treatment of tricuspid valve endocarditis are valve replacement or simple valve excision without valve replacement. A third more conservative procedure consists of resection of the vegetation ("vegetectomy") and leaflet repair, if necessary. Valve excision without valve replacement is described in adult patients especially in addicts of intravenous drugs, with normal ventricular function. Two cases of tricuspid valve endocarditis in children with interventricular communication successfully treated by "vegetectomy" and valve excision without valve replacement are reported. In the first case, surgery was performed during acute infection. Contrarily in the other case there was evidence that cure had been obtained, but still the prosthesis was not implanted due to the excellent hemodynamic status at the moment, and to abbreviate bypass time due to the preoperative conditions of the child. The uncommon approach to these two cases of tricuspid valve endocarditis in childhood motivated this presentation. PMID- 2597005 TI - [Use of isosorbide-5-mononitrate in acute myocardial infarction]. AB - Isosorbide mononitrate in a dose of 20 mg t.i.d. was used in 25 patients admitted few hours after acute myocardial infarction. The following parameters were analysed: systolic and diastolic blood pressure, heart rate, clinical features, and laboratory data. Heart rate and diastolic blood pressure remained unchanged, however systolic blood pressure was slightly reduced (p less than 0.01). There was a reduction in the angina episodes post-AMI. None of the patients included in the study had clinical deterioration or showed infarction extension. There were no changes in laboratory data. After the interruption of the drug, one patient died on the 6th day with acute mitral insufficiency. In conclusion, isosorbide mononitrate can be safely used during an uncomplicated acute myocardial infarction, without the risk of haemodynamic deterioration, and helps to prevent post-infarction angina. PMID- 2597006 TI - Tropical spastic paraparesis in Northeastern Brazil. AB - Ten possible cases of tropical spastic paraparesis (TSP) in Northeastern Brazil (Ceara) are presented. They show the typical symptoms and signs of TSP consisting of weakness of the lower limbs, spastic gait, hyperreflexia, bladder dysfunction and variable signs of posterior columns impairment. The laboratory examinations excluded other compressive, infective, degenerative or demyelinating lesions of their spinal cord. Our patients age ranged from 21 to 59 years, all were of black origin and all were of lower social class. There was a slight preponderance of females. An etiological implication of a retrovirus (HTLV-I) has been shown for TSP, but for lack of technical conditions we could not determine it in our patients, and that stands as our subsequent step in those and further cases. PMID- 2597007 TI - [Cranial computed tomography aspects in neurocysticercosis in childhood]. AB - The authors present the analysis of 27 computed tomography scans (CT) of 18 children which were divided in three groups according to clinical and tomographic criteria. Group 1 was characterized mainly by epilepsy and calcifications. Group 2 was characterized by intracranial hypertension and several tomographic aspects: edema, cysts and nodules were seen in three patients; hydrocephaly and calcifications were seen in two patients and CT was normal in one patient. Group 3 had patients with epilepsy or headache and variable tomographic patterns. The results are discussed based on the available literature. PMID- 2597008 TI - [An evaluation model of the cortical functions]. AB - The authors suggest a protocol elaborated to standardize the evaluation of high brain functions that should become an element for localization of cortical pathology. PMID- 2597010 TI - [Fibrous dysplasia of the skull: neurologic manifestations]. AB - The neurological manifestations of eight patients with osseous fibrous dysplasia of skull were retrospectively studied. In this series, the frontal bone was involved in 75% of the patients, the sphenoid or temporal bones in 37.5%, and the parietal in 25%. It was observed that cranial deformities occurred in all but one case, headache was present in 87.5% of the patients, visual disturbances in 50%, proptosis in 25%, and auditive symptoms in 12.5%. Six out of the eight patients were operated on: three of the four who presented progressive visual loss had postoperative improvement. In their follow up, none presented, until now, evidence of recurrence or worsening of symptoms, confirming the benign nature of fibrous dysplasia. PMID- 2597009 TI - [Pharyngeal pain during lateral suboccipital puncture]. AB - Oropharyngeal pain was referred by five fully conscious and collaborative patients during lateral suboccipital puncture (LSP) of the cisterna magna, performed for myelography and/or cerebrospinal fluid collection. The anastomotic connections between the lower cranial nerves, the sympathetic nerves and the upper cervical spinal nerves are reviewed, with emphasis on the relationship between the first cervical nerve (C1), the superior cervical ganglion of the sympathetic trunk, and the spinal accessory nerve (nerve XI), and their central connections. The authors conclude that pharyngeal pain during LSP is provoked by the stimulation of afferent visceral fibers of C1, or of the gray communicating branches of the superior cervical ganglion to C1. PMID- 2597011 TI - Severe optochiasmatic arachnoiditis after rupture of an internal carotid artery aneurysm. AB - The case of a 24-year-old man with progressive visual loss due to optochiasmatic arachnoiditis is presented. The cause of the arachnoiditis was subarachnoidal bleeding due to rupture of an internal carotid artery aneurysm. The aneurysm was clipped 5 years after the first episode of bleeding. The diagnosis of optochiasmatic arachnoiditis was confirmed during the operation. This case is presented in order to discuss the causes, the symptoms and the therapeutical possibilities of this rare condition. PMID- 2597012 TI - [Primary hematoma of the brain stem: considerations apropos of a case]. AB - The case of a 48 year-old woman presenting with a primary pontine hematoma is reported. The clinical evolution simulated a brain stem tumor and the diagnosis of hematoma was not established before the operation. The preoperative neurological deficit improved except for a facial nerve palsy. These hematomas are thought to be due to rupture of "cryptic" arteriovenous malformations and should be differentiated from those secondary to systemic hypertension. The diagnosis of brain stem hematomas should be considered in any case of brain stem lesion, especially in young and normotensive patients. PMID- 2597013 TI - [Epilepsy in ring chromosome 14 syndrome]. AB - A patient with ring 14 chromosome is reported. On the basis of this case and of a review of 28 cases published in the literature, the frequency of clinical signs and symptoms is determined, the constant and early incidence of epileptic seizures is emphasized and their characteristics are described. The associated congenital malformations are listed and their importance for karyotyping and consequent detection of new cases is emphasized. PMID- 2597014 TI - [Medullary paracoccidioidomycosis: report of a case]. AB - Paracoccidioidomycosis of the central nervous system presents either as meningeal or pseudotumoral lesions. Although occurring more frequently in the brain and meninges, they can occasionally involve the spinal cord. A case of paracoccidioidomycosis in the cervical spinal cord is reported in this paper. Difficulties in establishing the etiologic diagnosis, the importance of radiologic examination of the thorax, and the treatment of the patient are commented. In an extensive review of the literature on the subject, only three other cases have been found, which are also discussed. PMID- 2597016 TI - A transmission electron microscope study of fibroblast changes in human deciduous tooth pulp. AB - The coronal pulps of four primary canines, free from radicular resorption, and of three primary teeth, with roots entirely resorbed, were prepared for electron microscopy. Mature fibroblasts, similar to those reported in the pulps of permanent teeth, were present in the pulps of the clinically mature teeth. Regression of fibroblasts, evident in the pulps of deciduous teeth at the root resorption stage, was characterized by cytoplasmic changes, modifications in the cytoskeleton and dissociation of cells and fibrils. Deciduous teeth might provide a model for studying pulp fibroblast ageing. PMID- 2597015 TI - Bonnet syndrome and posterior parasagittal tumor: clues to neural mechanisms. AB - A case of Bonnet syndrome associated with blindness due to bilateral eye disease and a posterior parasagittal meningioma is reported. It is assumed that visual afferent deprivation alone is not enough to produce the syndrome and that, in most instances, a 'cerebral factor' must be operative if hallucinoses are to occur. The distinction between hallucinosis and hallucinations is favored and a common neural circuit for the mediation of hallucinotic imageries in general is suggested. One should not immediately put the blame on obvious eye or visual pathways affections when facing cases of Bonnet syndrome, as they are not likely to explain the complex array of images perceived by any given patient. On the contrary, the possibility of a clinically covert intracranial disease should be always raised and intensively looked for. PMID- 2597017 TI - Physico-chemical characteristics of mucus glycoproteins and lipids of the human oral mucosal mucus coat in relation to caries susceptibility. AB - Mucus coat was isolated from oral epithelial surfaces of caries-resistant and caries-susceptible subjects, analysed for content and composition of lipids and mucus glycoproteins, and evaluated for physico-chemical characteristics. The mucus coat from caries-resistant subjects had a protein content similar to that of the caries-susceptible group but a higher content of carbohydrate and a lower content of lipids and covalently bound fatty acid. The carbohydrate component was mainly mucus glycoprotein, which accounted for 28.4% of the dry weight of caries resistant mucus and 25.3% of caries-susceptible mucus. By chromatographic analysis on Bio-Gel A-50, both types of preparations had high (Mr approximately 2000 kdalton) and low (Mr approximately 300 kdalton) molecular-weight mucus glycoproteins. In the caries-susceptible mucus coat these two glycoproteins were in similar proportions, whereas the low molecular-weight glycoprotein predominated in caries-resistant mucus. In both preparations, the high molecular weight glycoprotein was characterized by a high content of carbohydrates, associated lipids and covalently bound fatty acids, whereas the low molecular weight glycoprotein was richer in protein and contained lesser amounts of associated and covalently bound lipids. Although the low molecular-weight glycoprotein showed only minor compositional differences with caries status, the high molecular-weight glycoprotein of the caries-resistant group had a 2.5 times lower content of covalently bound fatty acid, a 1.3 times lower content of associated lipids and contained 1.2 times more sulphate and sialic acid then that of the caries-susceptible group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2597018 TI - Tongue movement in the cat during the intake of solid food. AB - During feeding, solid food in the mouth progresses towards the pharynx during transport cycles, but it does not do so in chewing cycles. In the cat, the two cycle types differ with respect to jaw and hyoid movement but it is not known if, or how, any differences in tongue movement arise. This study sought to quantify the tongue movements in the different cycle types. Radio-opaque markers were placed in the midline of the cat tongue. While the animals ate solid food, the marker movements (viewed in the sagittal plane) were recorded by cine radiography. The movement of the tongue relative to the palate could be split into three components derived from (a) movement of the mandible, (b) movement of the hyoid, (c) movement produced within the body of the tongue itself. Although the differences in jaw movement between transport cycles and chewing cycles produced some differences in tongue movement relative to the palate, differences in the movements produced within the tongue itself were of greater significance. Transport cycles were characterized by rhythmic extensions of the tongue; the protracted tongue was about 60% longer than the retracted tongue. In chewing cycles, rhythmic length changes (viewed in the sagittal plane) were reduced and could be partly explained by an associated rotation of the tongue. In transport cycles the tongue, with food on it, was elevated to the palatal rugae as it extended, but when it shortened it was out of contact with the palate. It is suggested that these movements form the basis of a transport mechanism. PMID- 2597019 TI - The presence of microcalculi in normal human submandibular and parotid salivary glands. AB - A search for microcalculi in 10 submandibular and 10 parotid glands obtained from autopsies revealed them in 8 submandibular glands in all decades from the third to the seventh, and in one parotid gland in the fourth decade. They were found in serous acinar cells, striated ductal cells, lumina and interstitium. They may form in autophagosomes in parenchymal cells and usually pass into lumina to be expelled in the saliva. PMID- 2597020 TI - Collagenolytic and phosphatase activity in the rat mandible after functional protrusion. AB - The effect of chronic mandibular protrusion on the collagenolytic and phosphatase activity of several mandibular bone sites and the condylar cartilage was evaluated. Ninety-three male Sprague-Dawley rats were equally divided into two experimental and one control group. One experimental group wore a protrusive appliance for 2 weeks, the other for 4 weeks. All animals were killed at 59 days of age. Collagenolytic, alkaline and cid phosphatase activities were determined in the condylar cartilage, the subchondral bone and condylar neck, and in the gonial angle and coronoid process. In the cartilage and subchondral bone, the protrusive appliance caused a reduction in collagenolytic and alkaline phosphatase activity. In the condylar neck, it caused a large increase in collagenolytic activity and a decrease in alkaline phosphatase activity in both experimental groups. In the gonial angle and coronoid process, the appliance increased the collagenolytic activity only in the 2-week group. In the 4-week group, the alkaline phosphatase and collagenolytic activities were not different from the activities in those tissues in the control animals. Thus a protrusive appliance induced quantitative changes in enzyme activities in condylar cartilage and mandibular bone. The increase in collagenolytic activity (representing increased bone resorption) occurred typically in areas of muscle attachment and might have been the result of the neuromuscular changes induced by the protrusive appliance. The recovery to normal values of collagenolytic activity in the coronoid process and gonial angle of the 4-week group suggests that at these sites the muscles (and subperiosteal bone) might have adapted to their new biomechanical environment after the longer period of appliance wear. PMID- 2597021 TI - The effect of vibration on the discharge of periodontal ligament mechanoreceptors to controlled loading of the cat canine tooth. AB - This study observes the maximum 1:1 following frequencies of these mechanoreceptors, as well as their response characteristics before and after vibratory stimuli. Mechanical stimuli were applied to the tip of the crown of the left mandibular canine tooth in cats anaesthetized with alpha-chloralose while recordings were made from functionally single fibres teased from the inferior alveolar nerve. Vibratory stimuli were applied at various frequencies and durations at twice the threshold to that stimulus. Controlled ramp-plateau forces were applied before and after the period of vibration. A temporary rise in the receptor discharge was recorded and the threshold to ramp-plateau stimuli fell to about one-third of its original value. The increased post-vibration response was dependent on the frequency and duration of the stimulus. It is suggested that vibration has some temporary effect on the receptor environment. PMID- 2597022 TI - The effects of benzo(a)pyrene, nicotine, and tobacco-specific N-nitrosamines on the generation of human lymphokine-activated killer cells. AB - The effects of four major components of snuff (fine-cut smokeless tobacco) on the development of lymphokine-activated killer cells (LAK) were measured in vitro. Of the components tested: nicotine, N'-nitrosonornicotine, 4-(methylnitrosamino)-1 (3-pyridyl)-1-butanone and benzo(a)pyrene (BaP), only BaP suppressed LAK cytotoxicity against tumour targets and LAK DNA synthesis during 3- and 7-day incubations. BaP concentrations of 0.1-1.0 micrograms/ml suppressed lymphocyte proliferation only; there was no effect on tumour cell proliferation at these concentrations. BaP had no effect on tumour target killing when incubated during 4 h natural killer (NK) or LAK cytotoxicity assays. There was no effect on LAK binding of tumour targets after 3 days culture with BaP concentration of 0.1-1.0 micrograms/ml. These data confirm that a water-soluble extract of snuff has anti cytolytic and anti-proliferative effects on peripheral blood lymphocytes. As NK and LAK cells are important in preventing tumourigenesis and metastasis, suppression of these cells may favour neoplastic growth associated with snuff dipping. PMID- 2597023 TI - Adenine nucleotide changes in submandibular salivary glands of rats following isoproterenol or incisor tooth amputation. AB - Male rats (180-220 g) were injected daily with isoproterenol (2 mg/kg of body weight) for up to 6 days, or their incisor teeth were amputated on every other day for up to six amputations. The animals were subdivided into groups killed 12 or 24 h after the first or last intervention. In the development of sialadenosis caused by isoproterenol, the levels of ATP were greater (13-30%), while those of AMP were lower (13-19%) in the experimental groups. No variation was noted in ADP content. In tooth-amputated animals, only the five and six amputation subgroups showed higher values for ATP (approx. 17%), and ADP (12 and 15%, respectively). The inorganic phosphate level was lower in both experimental groups (between 11 28% for isoproterenol and 13-22% for amputation). Thus isoproterenol caused different metabolic responses in submandibular salivary glands from those induced by incisor amputation. PMID- 2597024 TI - Immunochemical quantitation of cysteine proteinase inhibitor cystatin C in inflamed human gingiva. AB - The amount of the low molecular-weight inhibitor, cystatin C, was determined by the enzyme-linked immunosorbent assay. Gingival tissue samples were obtained during periodontal surgery from 22 patients with different degrees of inflammatory periodontal disease, as indicated by gingival index and probing depth (PD). The concentration of cystatin C was in the range from 0.21 to 3.82 micrograms/g tissue and was significantly decreased (p less than 0.01) in samples taken from sites with increased PD. PMID- 2597025 TI - A quantitative study of the effects of chronic hypoxia on the histological structure of the rat major salivary glands. AB - Ten young adult female Wistar rats were placed in a decompression chamber at a simulated altitude of 5500 m for 28 days, after which they were killed and their salivary glands and thoracic organs were compared with those of eight matched control rats that had been maintained at sea-level atmospheric pressure. The prolonged hypoxic conditions were severe enough to induce structural changes in the heart and lungs of experimental rats, and their parotid and submandibular, but not sublingual, glands showed severe hyperaemic responses. However, no parenchymal changes occurred in any of the major salivary glands. The mean proportional volume of vascular tissue was increased by 57% in the parotid and 30% in the submandibular glands, and the mean intralobular capillary densities were also increased, by 29 and 18% respectively, in these two glands. The effectiveness of these vascular responses in protecting the salivary parenchymal elements against hypoxic degeneration probably reflects the high reserve potential normally present in salivary blood flow. PMID- 2597026 TI - A topographical study of the circadian rhythm in labelling index of mouse gingival and floor-of-mouth epithelium, including changes in labelling activity with individual cell position on the epithelial ridges. AB - A continuous strip of epithelium from the mandibular teeth to the ventral surface of the tongue of B6D2F-1 mice was examined autoradiographically after tritiated thymidine flash-labelling. Five areas were defined: area 1, the gingival sulcus epithelium adjacent to tooth enamel; area 2, the free gingival margin epithelium; area 3, the attached gingiva; area 4, the floor of mouth with undulating basement membrane; area 5, the floor of mouth with flat basement membrane. Data for the circadian variation in the proportion of DNA synthetic cells were recorded into a microcomputer, which enabled a large number of cells to be scored. The topographical position of each basal cell along the rete ridges and the incidence of labelling were noted. In each of the five areas a statistically significant circadian variation in labelling index (LI) was demonstrated, with a peak at 04.00-06.00 h and a trough at 20.00 h, although area 1 was slightly out of phase with the rest. The 24-h average LI values were almost double those obtained from a single flash-labelling at 10.00 h. The peak to trough ratio in LI was greatest in area 5 and fell towards area 1. Within the attached gingiva, cells deepest in the epithelial ridges had a larger peak to trough ratio than more superficial basal cells. For a group of mice labelled at 10.00 h the mean LI of the basal epithelial cells in areas 1-5 was 7.5 +/- (3.0)% (SD). Various aspects of the distribution of DNA synthesis in relation to topography were examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2597027 TI - Human dental plaque pH, and the organic acid and free amino acid profiles in plaque fluid, after sucrose rinsing. AB - The relationship between these factors was studied in plaque and plaque fluid samples taken at intervals during the Stephan pH curve following a sucrose mouth rinse. Levels of lactate rose after the rinse, then fell during the pH recovery phase. Levels of acetate, propionate and phosphate fell after rinsing, then rose again. Amino acid concentrations also changed, with many showing a fall followed by a rise; others rising then falling; and some showing a more variable or complex pattern. In resting plaque fluid, only alanine, proline, glutamic acid, glycine and ammonia were present at concentrations above 1 mmol/l. Delta aminovaleric acid was detected at levels below those that have been found in monkeys. Hydroxyproline and hydroxylysine were consistently detected, levels of arginine were generally low, and those of cystine consistently very low. The results may provide a basis for understanding the complex metabolic interrelations that occur in the course of the Stephan curve and which may reflect or produce the observed pH changes. They suggest that besides the amount of acid produced, the type of acid, buffering power and base production should be considered as determinants of plaque pH. PMID- 2597028 TI - The influence of saliva on infection of the human mouth by mutans streptococci. AB - The relationship between oral implantation of Streptococcus mutans IB1600 (serotype c) and Streptococcus sobrinus OMZ65 (serotype g), the aggregating activity of saliva, and its influence on the adherence of these bacterial strains in vitro was examined in seven human subjects. All the saliva samples aggregated strain IB1600 but not strain OMZ65 cells. Whole saliva from subjects with low levels of infection by Strep. mutans aggregated strain IB1600 to a greater degree than did whole saliva from those who were readily infected. Whole saliva from subjects most resistant to infection supported the adsorption of the highest number of either strain IB1600 or OMZ65 to hydroxyapatite surfaces. Thus the ability of whole saliva to aggregate Strep. mutans may influence the ability of these microorganisms to infect the mouth. PMID- 2597029 TI - Relationship of human gingival crevicular fluid polyamine concentration to the percentage of spirochaetes in subgingival dental plaque. AB - This relationship was examined at 45 inflamed periodontitis sites in 28 patients. A statistically significant positive correlation between polyamine concentration and spirochaetes was observed overall (r = 0.551, p = 0.0001). Within subgroups of this population (n = 15 each), there was no such relationship among midly inflamed sites with 5-6 mm probing depths (r = 0.0003, p = 0.999), but significant relationships among moderately inflamed sites with 5-6 mm depths (r = 0.567, p = 0.027) and 7-11 mm depths (r = 0.639, p = 0.010). Thus polyamines may be involved in subgingival plaque homeostasis at moderately inflamed periodontal sites. PMID- 2597030 TI - The response of Langerhans cells to palatal cover plates in the rat. AB - It is not known whether the long-term use of prosthetic or orthodontic appliances, which may be associated with fungal infections, affects Langerhans cells (LC) in the underlying mucosa. The number and distribution of LC was studied in rat palatal epithelium over a 7-day period after insertion of cover plates. Smears of cultures taken before and at the end of the experiment were examined for fungi. LC were identified in cryostat sections using an immuno alkaline phosphatase technique to demonstrate cell surface Ia (Class II Major Histocompatibility Complex antigens). Occluding the palate predisposed to food trapping and microbial growth. Fungi were recovered from the plates of two animals but not from control or experimental animals before fitting the plates. No differences in LC numbers were found on days 1 and 3 after insertion of the plates, but a significant increase was observed on day 7. It is not known whether this change represents a true increase in LC number or an increase in Ia expression, but it is likely to be the response to an alteration in the number and/or nature of antigens penetrating the mucosa because of microbial growth and food retention. PMID- 2597031 TI - The intrusive mobility of the incisor tooth of the guinea pig. AB - The pattern of mobility of the mandibular incisor with intrusive loads was consistent with the view that the periodontal tissues are viscoelastic. A significant time-dependency of the response was observed. The pattern of mobility was similar to that reported for axially directed extrusive loads and for horizontal loads. PMID- 2597032 TI - Promotion of osteogenesis by extra-embryonic epithelial in maxillary mesenchyme of the embryonic chick. AB - Maxillary mesenchyme (HH stages 19-21), separated from its epithelium and grown as a graft on the chorioallantoic membranes of host chick embryos, did not form membrane bone. However, when isolated maxillary mesenchyme was recombined directly with chorioallantoic endoderm or chorioallantoic ectoderm and then grafted, it did form membrane bone in 87.5 and 70% of cases, respectively. This novel finding of extra-embryonic epithelia eliciting an osteogenic response from membrane bone-forming mesenchyme indicates that the germ-layer origin of an epithelium does not necessarily restrict its potential to promote membrane bone formation. PMID- 2597033 TI - Effect of experimental stress on masseter and temporalis muscle activity in human subjects with temporomandibular disorders. AB - Temporomandibular (TM) disorders have an uncertain aetiology. The purpose of this study was to replicate and extend the work of Yemm (1969) (Archs oral Biol. 14, 873-878, 1437-1439; Br. dent. J. 127, 508-510), who reported a lack of habituation to experimentally induced stress in subjects with TM disorders. In this study, 20 TM disorder patients and 20 controls, matched for age and sex, performed a timed psychomotor task while bilateral masseter and anterior temporalis electromyographic (EMG) activity, finger temperature and skin admittance were monitored. These data were sampled, stored every 4s and averaged by an Apple II Plus/ISAAC interface. A significant trials effect for finger temperature (F[4/152] = 34.99, p less than 0.001) and skin admittance (F[4/152] = 41.90, p less than 0.001) was found, suggesting that the independent variable (stress) had been successfully manipulated. A significant trials by groups effect was found for right temporalis EMG activity (F[3/144] = 3.94, p less than 0.05); the left temporalis showed a similar, but not significant, trend. The masseter muscles did not show differences or trends between groups. No significant differences were found in resting EMG levels or in the initial magnitude of EMG responses during baseline. These results provide support for the hypothesis that TM disorder and control groups respond differently to stress in terms of habituation to stressful stimuli. PMID- 2597034 TI - Site-specific variations in the biochemical composition of healthy sheep periodontium. AB - A topographical biochemical analysis of the periodontal soft tissues was carried out. The protein distribution in the tooth-supporting structures was determined from site by amino acid analysis and was compared with the collagen distribution in tissue protein, based upon hydroxyproline content. The biochemical composition of the periodontal ligament was heterogeneous but some specific patterns of protein and collagen distribution emerged. Protein concentration was highest at the gingival epithelium and adjacent to the cementum. Collagen concentrations were highest at the alveolar bone and below the junctional epithelium adjacent to the tooth. Such patterns may influence the way in which periodontal disease is propagated through the tissue. PMID- 2597035 TI - Proton microprobe determination of fluorine profiles in the enamel and dentine of erupting incisors from sheep given low and high daily doses of fluoride. AB - Developmental defects in incisors were induced by daily oral ingestion of sodium fluoride solutions. Teeth extracted at eruption from sheep that had been subjected to four different fluoride regimens--0.2 or 0.5 mg F/kg body weight daily for 6 months, 2 or 6 mg F/kg body weight daily for 21 days--were analysed for fluorine by gamma emission using a proton microprobe. Calcium and zinc profiles were also measured using proton-induced X-ray emission. Diffuse opacities, similar in appearance to mild human fluorosis, were produced by the first two regimens, whereas the last two produced hypoplastic lesions. Different distributions of fluoride were found in the unerupted enamel and dentine, and these patterns reflected variations in both the duration and concentration of the fluoride dose used to induce the fluorotic lesions. PMID- 2597036 TI - Spacing in the human deciduous dentition in relation to tooth size and dental arch size. AB - Dental casts of 243 preschool children, 129 males and 114 females, aged 2.5-5.5 years, were analysed for the presence of interdental spaces, mesiodistal crown diameters, intercanine width, intermolar width and arch length (circumference). The prevalence of primate spaces (diastemata mesial to the upper canines and distal to the lowers) varied from 65 to 90% by arch and sex; it was lowest in the lower arch especially in females, and highest in the upper. These prevalences did not increase with age; however, other spaces which usually occur between incisors may develop towards the end of the deciduous dentition, commonly in arches with primate spaces. Generally, spacing of the deciduous anterior teeth was significantly related to mesiodistal crown diameter and intercanine arch width. The crowns were significantly broader and the arches significantly narrower in cases with no spaces than in those where spaces existed. As the genetic programming for tooth size also normally affects arch size, greater discrepancies between mesiodistal crown diameters of the deciduous anterior teeth and their permanent successors are probably associated with more deciduous arch spacing. PMID- 2597037 TI - Reduction in sympathetic neuronotrophic activity in the pulp of the cat canine tooth after denervation. AB - Most of the nerve fibres supplying the mandibular canine on one side were interrupted by sectioning the inferior alveolar nerve (IAN) and, after 1 week, the trophic activity in each mandibular canine pulp was assessed in an in vitro assay using sympathetic neurones from 11-day chick embryos as test cells. In eight of nine animals tested, neuronotrophic activity in the denervated pulp was markedly lower than in the contralateral control pulp. Antiserum to mouse nerve growth factor had no effect on the trophic activity in either control or denervated pulps. Thus, the pulp differs from other peripheral tissues, which undergo increases in neuronotrophic activity after denervation. The basis of this difference may be the high innervation density of the pulp. The IAN distal to the site of nerve transection also had reduced survival-promoting activity. PMID- 2597038 TI - Activation of human natural killer cells by lipopolysaccharide from Actinobacillus actinomycetemcomitans. AB - Lipopolysaccharide (LPS) from the Y4 strain of this bacterium, which is implicated in the pathogenesis of juvenile periodontitis, was incubated with human peripheral blood lymphocytes (PBL) and its action compared to that of LPS from Escherichia coli. Both LPS augmented cytotoxicity measured against natural killer (NK) cell-resistant tumour targets within 24 h of incubation. Cytotoxicity was exclusively found in NK-enriched low-density large granular lymphocyte fractions, as separated by Percoll gradient. LPS activated NK cells without stimulating high levels of proliferation. The minimum concentration of A. actinomycetemcomitans LPS required to activate NK cells was 1 microgram/ml; higher concentrations did not significantly increase this activation. LPS had no synergistic effect on the induction of PBL cytotoxicity by interleukin-2. In contrast, LPS pre-activated monocytes inhibited the induction of lymphocyte cytotoxicity by either interleukin-2 or LPS. PMID- 2597039 TI - Morphogenesis of mineralized tissues induced by neonatal mouse molar pulp isografts in the spleen. AB - Tooth pulps dissociated intact with EDTA were isografted for up to 40 days, and examined by light and electron microscopy for hard tissue morphodifferentiation. Grafts formed tubular dentine and osteodentine. Tubular dentine, penetrated regularly by elongated odontoblast processes, resembled normal dentine and was formed when the original odontoblasts continued normal matrix secretion. Osteodentine was formed by spindle-shaped cells with large round nuclei which presumably were transformed pulp cells, and incorporated the same elements as found in cells of non-tubular dentine. Occasionally, odontoblasts were contiguous with both the regular dentine and the osteodentine. Thus in EDTA-dissociated pulps transplanted to the spleen, the original odontoblasts produce tubular dentine and other pulp cell differentiate to form osteodentine. PMID- 2597040 TI - The polarized light microscopy and ultrastructure of Polynesian pigmented tooth enamel. AB - Transmitted and polarized light microscopy of unerupted and erupted teeth affected by a pigmented anomaly found in two geographically isolated Polynesian populations, the New Zealand Maori and the French Polynesian Marquesas Islander, showed similar histological characteristics. Mounted in water, the pigmented areas were positively birefringent and covered with a thin negatively birefringent surface layer 200-250 microns thick. Cervical areas were negatively birefringent. Transmission electron microscopy of argon-ion-beam thinned specimens of affected enamel revealed large voids, disruption in the packing of crystals and spacing at prism boundaries. In the surface layer of enamel from erupted and unerupted teeth, the intra- and interprismatic spaces were occluded by fine crystals or amorphous material. A well-defined prism structure and close crystal packing were found in cervical enamel. The ultrastructure of these pigmented enamels was similar to and consistent with a hypomaturation type of amelogenesis imperfecta. PMID- 2597041 TI - A histometrical analysis of age changes in the human lingual artery. AB - The lingual arteries from 450 Japanese autopsies, ranging in age from 3 months to 106 years, were carefully selected for examination of the ageing process. Histopathologically, a focal intimal thickening, considered to be an intimal cushion rather than an atheromatous lesion, was observed in cases as young as 6 month-old infants. The most frequent intimal change was diffuse fibrous thickening, present throughout the life span. Luminal obstruction caused by extensive atheromatous plaques was never seen. The internal elastic lamina regressed with increasing age. Histometrically, the radius of the artery increased not only during the developmental period but also after maturation, with a modified exponential curve. The thickness of the media also increased with a modified exponential curve until the third decade, when it became fairly constant. The thickness of the intima increased exponentially throughout the life span. The value of the relative luminal radius, considered to be an index value for arterial senescence, remained constant until the seventh decade and then showed a distinct decrease. This luminal narrowing, resulting primarily from intimal thickening, was compensated for by outward growth of the media and remodelling of the internal elastic lamina with increasing age until the seventh decade. The changes in the dimensions of both media and intima, and the histopathological alterations in the lingual arterial wall with progressing age, suggest that disturbances of homeostasis in the media play an important role in age-related progression of arteriosclerotic change. PMID- 2597042 TI - Effects of a low calcium maternal and weaning diet on the thickness and microhardness of rat incisor enamel and dentine. AB - The deposition and mineralization of incisor hard tissues have been studied in rat pups nursed by mothers on a low calcium diet or weaned with the maternal diet. Animals were killed at 30 days (control and low calcium diets; maternally fed) or 60 days (after 30 days weaning on maternal diet). The degree of mineralization of enamel and dentine was evaluated by a microhardness method on thick transverse sections. The enamel and dentine thickness, and the diameters of the incisor sections and pulp cavity were measured on microradiographs from the sections. Microhardness values of enamel were similar in groups killed after 30 days maternal feeding, but the microhardness of root enamel was 73-74% less in the low calcium-diet weaned group. Peripulpar dentine had mean microhardness values lower than controls in the group fed maternally for 30 days, whereas the whole root dentine appeared significantly less hard in the low calcium-diet weaned group than in the controls. A significant reduction of the incisor bucco lingual diameter was observed only in this last experimental group. Enamel thickness was significantly lower in the roots of both experimental groups and in the necks of the low calcium weaned group. The reduction in dentine thickness was greater (from -30 to -56%); in the root it was more evident on the lingual aspect. Thus calcium deficiency in the mother's diet did not influence either the deposition or the mineralization of the pup's incisor enamel and dentine. However, when the offspring were weaned with the maternal calcium-deficient diet, mineralization of the tooth hard tissue was retarded. PMID- 2597043 TI - Relationships between human parotid saliva lysozyme lactoferrin, salivary peroxidase and secretory immunoglobulin A in a large sample population. AB - Saliva antimicrobial proteins may interact in a common system for host defence. This study applied multivariate analysis as a means of describing inter-person variation in that system. Samples of stimulated parotid saliva were obtained from 198 subjects. Flow rate was determined, and assays run for total protein, lysozyme, lactoferrin, salivary peroxidase and secretory IgA. Correlation and principal components analysis were used to define the relationships between proteins; cluster analysis was used to identify persons with similar protein concentration profiles. All proteins were significantly correlated at p less than 0.002 (r = 0.20-0.52). Principal components analysis identified a major axis of common variation, defined by lysozyme and salivary peroxidase, and a second axis, defined by secretory IgA. Lactoferrin was associated with both axes. Seven major groupings were obtained by cluster analysis; these were significantly different at p less than 0.001. Such groupings may prove useful in comparing the antimicrobial properties of saliva samples. PMID- 2597044 TI - Piezoelectricity in cementum, dentine and bone. AB - Unlike the dental hard tissues, bone remodels when subjected to orthodontic forces. Bone is also piezoelectric (generates a surface electrical charge upon application of force). In dentine and cementum from sperm whale teeth (which gave samples of sufficient size), the existence and magnitude of piezoelectricity were examined and compared with human bone. Both dental tissues were found to be piezoelectric with coefficients of 0.027 and 0.028 pC/N, respectively; the coefficient of human bone was eight times greater (0.22 pC/N). Thus the strength of the piezoelectric effect was correlated with the known capacities of the tissues to undergo adaptive remodelling. This result is consistent with the theory that piezoelectricity mediates orthodontically induced alveolar remodelling. PMID- 2597045 TI - A morphometric and quantitative microradiographic study of dental tissues in the hypopituitary dwarf mouse. AB - In transverse sections the areas of enamel, dentine and pulp were determined using image analysis morphometry, and the mineralization levels of enamel, dentine and alveolar bone using quantitative microradiography and a microphotometric-microdensitometric technique. There were significant differences in the ratios of dentine to pulp area, and in the enamel to total area in the incisors from dwarf and normal animals. The mean dentine to pulp ratio for dwarf incisors was more than six times greater than in normal incisors. There was also a significantly greater variation in the dentine to pulp ratio in dwarfs, which was attributed to their greater variation in pulp size. Values for mineral density of enamel, dentine and bone were similar to those found by other investigators. For example, for normal specimens, the mean mineral density of outer enamel was 2.84 g/cm3 (SD = 0.38), percentage mineralization 92%; outer labial dentine was 1.64 g/cm3 (SD = 0.15), percentage mineralization 52%; and alveolar bone was 1.53 g/cm3 (SD = 0.13), percentage mineralization 49%. The variation in mineralization within each tissue confirmed previous work in rodents. There was a consistent trend for mineralization levels of all hard tissues in the dwarf sample to be less than in the normal sample but the difference was not statistically significant for any one tissue. PMID- 2597046 TI - Cloning of the gene for cell-surface protein antigen A from Streptococcus sobrinus (serotype d). AB - A gene library of Strep. sobrinus B13N (serotype d) chromosomal DNA was constructed in Escherichia coli, with the bacteriophage vector lambda L47.1. A recombinant phage, lambda MDSM49, containing a 15.5 kb DNA insert, directed the expression of a 210 kDa antigenic protein. The recombinant 210 kDa protein was shown by Western blot analysis to be identical with cell-surface protein antigen A (spaA) from a serotype g strain. However, the restriction patterns of a subclone plasmid, pMD51, from lambda MDSM49 differed from those of serotype g strain. The cell-surface protein antigen I/II from serotype c Streptococcus mutans is a potential immunogen for vaccination against dental caries and corresponds to the spaA from serotype d and g strains. A recombinant clone, pDM51, will be a useful tool for serological and molecular biological studies. The recombinant spaA provides useful material for assessment of its diagnostic and immunogenic potential. PMID- 2597047 TI - An adaptation of the Lashley cup for use in rat saliva collection. AB - A miniaturized Lashley cup for collecting rat parotid and submandibular/sublingual saliva is described. The small dimensions of the cup enabled its proper positioning on the orifices of both salivary ducts. The method avoids surgical intervention, causes no tissue damage, allows simultaneous collection of both types of saliva and its appropriate for long-term studies of salivary composition and secretion in the rat. PMID- 2597048 TI - Collagenolytic activity of the extracellular vesicles of Bacteroides gingivalis W50 and an avirulent variant W50/BE1. AB - The activities of the extracellular vesicle fractions of these two organisms were compared. Lytic activity against a native type I placental collagen substrate at 30 degrees C was assessed following sodium dodecyl sulphate-polyacrylamide gel electrophoresis and densitometry. A rapid rate of collagen depolymerization was achieved by the extracellular vesicle fraction of W50, yielding approx. 90% substrate degradation compared to 5% for W50/BE1 extracellular vesicles over 6 h incubation. The polypeptide digestion patterns produced by incubation with extracellular vesicle fractions of both organisms were identical, and similar to those yielded by incubation of substrate with whole W50 cells. PMID- 2597049 TI - A biochemical study of glycosaminoglycans in the palatal rugae of the monkey (Macaca fascicularis). AB - Glycosaminoglycans (GAG) were extracted from the connective tissue of the palatal rugae, separated by electrophoresis and compared with the results obtained for the remaining palatal mucosal and gingival connective tissues. The GAG content of the rugae (3.01 mg/g defatted dry weight) was higher than in the remaining palatal mucosa (2.33 mg/g defatted dry weight) or gingiva (1.68 mg/g defatted dry weight). Dermatan sulphate was the predominant GAG in both the palatal rugae (48% of total GAG) and the remaining palatal mucosa (50%) followed by hyaluronic acid (33 and 31% respectively). The results do not support previous histochemical observations in which the rugae appeared to be rich in hyaluronic acid. PMID- 2597050 TI - Zinc and strontium analyses by energy dispersive X-ray fluorescence in human permanent teeth. AB - The zinc and strontium content of enamel and dentine from humans aged 9-64 yr was analysed, after systematic sampling, by X-ray fluorescence. Relatively high levels of zinc were found in both hard tissues but there was no significant increase with age. Zinc content decreased significantly from outer to inner enamel and increased significantly again from peripheral to pulpal coronal and root dentine. The strontium content was significantly higher in enamel than in dentine; there was a significant increase with age in enamel but not in dentine. However, outer and inner enamel showed no significant difference in strontium content. Almost similar amounts of strontium were found in coronal and root dentine. PMID- 2597051 TI - Localization of two distinct acid phosphatases in secretory ameloblasts of rat molar tooth germs. AB - Acid phosphatases were examined histochemically at the light- and electron microscopic levels using para-nitrophenyl phosphate (pNPP) and beta glycerophosphate (beta-GP) as substrates. By light microscopy, there was intense activity with pNPP in supranuclear and distal regions of the secretory ameloblast, and moderate or slight activity respectively in those regions with beta-GP. These enzyme activities were less at the late secretory stage of amelogenesis and disappeared at the transitional stage. By electron microscopy, acid phosphatase activity was seen in the trans side cisternae of the Golgi apparatus, in lysosome-like granules, and in small vesicles in the Tomes' processes. The activity with pNPP but not beta-GP was also localized at the plasma membrane (proximal, lateral and distal surface). Activity with beta-GP was completely inhibited by 1 mM sodium tartrate and by 1 mM NaF; activity with pNPP was inhibited by 1 mM NaF and 10 mM sodium tartrate, but not by 1 mM sodium tartrate. Thus there are at least two different acid phosphatases, one tartrate sensitive and the other 1 mM tartrate-resistant, in the secretory ameloblast; the tartrate-resistant enzyme is plasma-membrane bound. PMID- 2597052 TI - Antagonism of fluoride toxicity by high levels of calcium but not of inorganic phosphate during secretory amelogenesis in the hamster tooth germ in vitro. AB - Whether the interference by fluoride (F-) with secretory amelogenesis in vitro could be modulated by altering the levels of calcium (Ca) and inorganic phosphate (P) in the medium was investigated. Hamster first upper molar tooth germs in the secretory phase of amelogenesis were exposed to 10 microM-1.31 mM (0.2-25 parts/10(6)) of F- in vitro for 2 days in the presence of either low (1.2 mM), moderate (2.1 mM) or high (4.1 mM) levels of Ca, or moderate (1.6 mM) and high (3.6 mM) levels of P. The biosynthesis and secretion of enamel matrix proteins under each of the experimental conditions were examined by labelling with [3H] proline during the last 24 h of culture, and mineralization by labelling with 45Ca and [32P]-orthophosphate. With moderate levels of Ca and P (control medium), F- increased the uptake of 45Ca and 32P in a dose-dependent manner; F- did not inhibit the synthesis of matrix proteins but to a moderate extent impaired their secretion. In explants grown in the presence of 52 microM of F- the superficial layers of enamel matrix deposited in vitro (fluorotic matrix) failed to mineralize. Increasing P levels in the medium had no clear histological effect, whereas lowering Ca levels sometimes seemed to aggravate the F- effect. Raising Ca levels improved the histological pattern: in spite of the presence of F-, high Ca levels allowed a limited mineralization of the superficial layer of fluorotic matrix along with a strong rise in mineralization of the deeper layers of pre exposure enamel. High Ca levels also considerably reduced the cellular changes in secretory ameloblasts induced by 52 microM of F- and slightly counteracted the inhibition of matrix secretion, as measured biochemically. Some of the effects of F- on secretory amelogenesis in vitro can thus be reversed by raising Ca levels in the medium. Therefore, the effect of F- on secretory amelogenesis in vitro seems to be primarily interference with the enamel mineralization process per se and, secondarily, an impairment of matrix secretion. PMID- 2597053 TI - Toffee clearance and lingual sensory and motor activities in normal children and in children with articulation problems of speech. AB - The rate at which a standardized mouthful of toffee containing technetium (99mTc) tin colloid was cleared from the mouth during and after chewing was measured by counting the residual radioactivity in the mouth at short time intervals by external gamma counting. The clearance curve was resolved into three phases for each subject--chewing time (1), which coincided with the time to reach 10% of the initial counting rate, scavenging time (2), and a final slow diffusion phase (3). Although the mean chewing time was only 1.9 min, the technique allowed the pattern of clearance during this phase to be assessed for each of 10 normal children (mean age 11.1 yr) and 7 children (mean age 11.0 yr) diagnosed as having delayed articulation. Two measurements of sensory and motor functions of the tongue were made on the same subjects. These measurements were of oral stereognosis and tongue-tip manipulation. Within the control group, only the correlation between stereognosis error scores and the duration of phase 1 or phases 1 and 2 combined was statistically significant. The mean stereognosis and tongue manipulation scores were significantly lower in the poor articulation group than in normal children but, with one notable exception, the clearance curves were similar. PMID- 2597054 TI - Comparison of jaw-opening reflex response elicited by anterior and posterior tooth tapping in the cat. AB - The response elicited by various levels of controlled mechanical stimuli to maxillary teeth was studied in 8 adult cats anaesthetized with alpha-chloralose. When an anterior tooth was tapped, short (4-6 ms) and long (16-20 ms) latency responses were recorded from the mylohyoid nerve. On the other hand, when a posterior tooth was tap-stimulated, only the long-latency response was induced. The effects of ether narcosis on the responses were studied. As the short-latency response was induced only by anterior tooth tapping and its amplitude increased according to increases in stimulus intensity, the response may be related to the protection of the mouth from entrance of harmful materials. The long-latency response was induced by light tapping on both anterior and posterior teeth and its amplitude increased according to increases in stimulus intensity to the posterior teeth rather than the anterior teeth. As it was readily inhibited by ether, the long-latency response may have a reflex centre in an area like the brain stem reticular formation which is particularly sensitive to ether and may be related to the regulation of jaw movement in mastication. PMID- 2597056 TI - Haemoglobin concentration and oxygen saturation in dog gingiva with experimentally induced periodontitis. AB - The index of haemoglobin concentration (Hb index) and apparent oxygen saturation (apparent SO2) were determined by a new, non-invasive method, tissue reflectance spectrophotometry. The Hb index was positively correlated with the haemoglobin concentration. The relationship between the apparent SO2 and oxygen partial pressure was a sigmoid curve resembling the haemoglobin oxygen dissociation curve. The Hb index and the apparent SO2 were monitored continuously by tissue reflectance spectrophotometry during the induction of experimental periodontitis with silk ligatures. The Hb index increased rapidly during the first 7 days after ligation and then decreased gradually during the remaining period. The apparent SO2 decreased during the first 7 days but gradually rose during the final 9 weeks. The maximum level of the deoxyhaemoglobin concentration after ligation was elevated about two times over that found before ligation, whereas the increase in oxyhaemoglobin concentration was relatively small. These results suggest that the oxygen supply to inflamed gingiva may increase to some extent, but not sufficiently to compensate for the increased oxygen consumption. PMID- 2597055 TI - Antigens of Actinobacillus actinomycetemcomitans identified by immunoblotting with sera from patients with localized human juvenile periodontitis and generalized severe periodontitis. AB - Sonicated whole cell extracts and outer membrane proteins from this bacterium were analysed using sera from 31 young patients with localized juvenile periodontitis, 55 young adults with generalized severe periodontitis and from 31 healthy control subjects. The sonicate contained 13 major bands (14-78 kDa); a greater proportion of sera from patients with generalized periodontitis reacted with 40 and 70 kDa antigens when compared with sera from localized juvenile periodontitis and controls. In contrast, a lower proportion of sera from localized juvenile periodontitis reacted with the 29 kDa antigen when compared with severe periodontitis and controls. The outer membrane proteins contained four main antigens of 19, 24, 35 and 67 kDa, which reacted with sera from all three groups. Although, so far, the findings do not allow discrimination between the two diseases, antibody responses to the 29, 40 and 70 kDa antigens of A. actinomycetemcomitans may help in the assessment of severity of the disease in patients with periodontitis. PMID- 2597057 TI - Effects of molybdenum on human enamel fluoride uptake and experimental rat dental caries. AB - The addition of high concentrations of molybdenum to a topically applied sodium fluoride solution did not result in a statistically significant increase in fluoride uptake into subsurface lesions in human enamel when compared to that after treatment with fluoride alone in vitro. The addition of 3000 parts/10(6) molybdenum to a 1000 parts/10(6) fluoride topical solution had no impact in vivo on the cariostatic activity of topically applied fluoride in rats. PMID- 2597058 TI - Variation in human salivary pellicle formation on biomaterials during the day. AB - Contact angle measurements were used to study the effects of pellicle formation on polymethyl-methacrylate, dental amalgam and gold. Samples were exposed to saliva in vivo for periods of 5-20 min at three separate occasions during the day. Pellicle drastically increased the wettability of all the materials and effectively sealed off the effect of the original surface activity. Variation in pellicle formation during the day was demonstrated. Pellicles formed at midday showed the least reduction in contact angles compared to those formed during the morning and afternoon. This difference coincided with an increased concentration of inorganic phosphate in saliva at midday. The method enables comparative studies of pellicle formation on hard biosurfaces. The findings indicate differences in the physical behaviour of saliva during the day, and illustrate the importance of making adhesion studies with this variation in mind. PMID- 2597059 TI - In vitro characterization of human salivary lubrication. AB - The friction coefficients for parotid and submandibular-sublingual salivas of 7 subjects were measured. At the load and speeds used, the lubricatory properties of the secretions followed the McKee-Petroff's curve. The friction coefficients for both secretions approximated those reported for boundary and thin film lubrication. PMID- 2597060 TI - Aicardi's syndrome. PMID- 2597061 TI - Denatured alcohol is not toxic for the eye. PMID- 2597062 TI - A mannequin for teaching ocular fundus examination skills. PMID- 2597063 TI - Bull's-eye corneal lesion resulting from war game injury. PMID- 2597064 TI - Crystal deposition following keratoplasty in nephropathic cystinosis. PMID- 2597065 TI - Optic nerve decompression may improve the progressive form of nonarteritic ischemic optic neuropathy. AB - Optic nerve sheath decompression surgery improved visual function for 12 of 14 patients with progressive nonarteritic ischemic optic neuropathy (NAION). Visual recovery was maintained in all patients during a follow-up period of 6 to 18 months (average, 11 months). Seven patients had experienced a previous NAION in the eye that was not operated on that did not improve spontaneously. Surprisingly, 2 of these 7 eyes with long-standing decreased vision demonstrated some visual improvement after surgery on the contralateral, acutely affected eye. Spontaneous visual improvement did not occur in an age- and sex-matched control group of 12 patients with similar entry-level visual acuity and field loss. Only 1 of 3 patients with sudden, nonprogressive visual loss secondary to NAION improved after surgery. In a control group with nonprogressive NAION, 2 of 15 eyes (14 patients) demonstrated spontaneous improvement. Optic nerve sheath decompression improves visual loss due to progressive NAION, a disorder without any previously effective therapy. However, for acute, nonprogressive NAION, surgery for a small number of patients did not improve the natural history of the disease. PMID- 2597066 TI - Should recessions of the medial recti be graded from the limbus or the insertion? AB - In a series of 27 patients who were operated on for esotropia, we compared patient response to surgery and the distance the medial recti were recessed from the insertion and corneoscleral limbus. We found a much more significant correlation between the response and the amount the muscles were recessed from the insertion than from the corneoscleral limbus. Using partial correlation coefficients, we found that when we corrected for the amount of recession from the insertion, there was not a significant correlation between the response to surgery and the amount the muscles were recessed from the corneoscleral limbus. This suggests that the apparent correlation between the response to surgery and the amount of recession from the corneoscleral limbus simply reflects that the greater the recession from the corneoscleral limbus, the farther the muscle is likely to end up posterior to the insertion. PMID- 2597067 TI - Neodymium-YAG laser goniotomy vs surgical goniotomy. A preliminary study in paired eyes. AB - Goniotomy and trabeculotomy are two widely accepted modalities of treatment for primary congenital/infantile glaucoma. Both procedures may be associated with complications. We treated 10 patients with bilateral, symmetrical congenital/infantile glaucoma and clear corneas. One eye of each patient underwent surgical goniotomy under general anesthesia, and the other was treated by neodymium-YAG laser goniotomy under oral chloral hydrate sedation (average energy, 76.6 mJ). Mean pretreatment intraocular pressure in the surgical goniotomy group was 28.4 mm Hg and in the laser goniotomy group it was 29.5 mm Hg, decreasing to 23.6 and 23.1 mm Hg, respectively, following treatment. There was a strong positive correlation (r = .81) between the percent of intraocular pressure change after laser treatment (mean, -14.4%) and that after surgery (mean, -14.3%). Our preliminary results indicate that neodymium-YAG laser goniotomy is an effective, noninvasive alternative to surgical goniotomy. PMID- 2597068 TI - The relationship of retinal microaneurysm counts to the 4-year progression of diabetic retinopathy. AB - The relationship of retinal microaneurysms to the progression of diabetic retinopathy over a 4-year period was examined in a population-based sample of diabetic persons. The number of microaneurysms in color stereoscopic fundus photographs of seven standard fields was counted in the eyes of diabetic persons (n = 236) who had only microaneurysms in photographs at the baseline examination. If only one eye was involved (n = 121), the mean number of microaneurysms was 2.3; with bilateral involvement (n = 115), the mean was 9.3 in the more involved eye. The number of microaneurysms at the baseline examination was positively associated with significant progression of retinopathy. This relationship remained after controlling for the level of glycosylated hemoglobin. These data suggest that the number of microaneurysms at baseline is an important predictor of progression of diabetic retinopathy. Microaneurysm counts may prove to be a useful early end point in clinical trials. PMID- 2597070 TI - Corneal healing following laser refractive keratectomy. AB - A 193-nm excimer laser system was used to ablate 4.5-mm optically contoured zones in the corneal stroma of rabbits to achieve optical flattening of 2, 4, 8, and 16 diopters. We studied the effect of edge profile and wound depth on reepithelialization and stromal remodeling using dichlorotriazinyl aminofluorescein, a vital dye that covalently binds to the stromal bed and delineates the boundaries of new collagen synthesis. All the corneas reepithelialized; no subsequent recurrent erosions occurred. All seven corneas that received an ablation of less than 50 microns were clear centrally at 8 weeks. At an ablation depth of approximately 100 microns, opacification and scarring were observed biomicroscopically and histopathologically in two specimens. No evidence of new collagen formation or epithelial hyperplasia was found in any of the seven corneas that remained clear. Stromal remodeling was observed in the two corneas that exhibited scarring. PMID- 2597069 TI - Variability of depth measurements of the optic nerve head and peripapillary retina with computerized image analysis. AB - Computerized topographic mapping of 10 repeated fundus images of one eye each in 10 healthy subjects and in 10 subjects with elevated intraocular pressures (IOPs) was performed with the Humphrey Retinal Analyzer. The variability of depth measurements at 400 to 650 individual locations in the optic nerve head and peripapillary retina was evaluated. The average size of the 95% confidence intervals for individual depth measurements for healthy subjects and those with elevated IOPs were 166 and 232 microns in the optic nerve head and 205 and 261 microns in the peripapillary retina, respectively. Variability was significantly less for healthy subjects than for those with elevated IOPs. Variability was significantly greater for depth measurements in the peripapillary retina than for measurements in the optic head. Knowledge about variability of individual depth measurements is useful for proper interpretation of computerized topographic mapping to detect retinal nerve fiber damage. PMID- 2597071 TI - Cell division in the healing of the corneal endothelium of cats. AB - The pattern of cell division of the corneal endothelium of cats was studied during the first week following scraping of 35.2% to 38.3% of the endothelial cells. A small number of mitoses were found 2 days after scraping (mean +/- SD, 8.2 +/- 6.1 per cornea); the number peaked during the third and the fourth days (148.5 +/- 74.5 and 206.8 +/- 40.1, respectively), sharply decreased on the fifth day to a level of 17.0 +/- 9.5, and further decreased on the sixth and seventh days to 4.2 +/- 1.8 and 3.3 +/- 1.5 mitoses per cornea, respectively. Due essentially to amitotic cell division, a multinuclear cell population, mainly binuclear, appeared and increased to a number of 3999 +/- 746 and 3,129 +/- 877 on the sixth and seventh days, respectively, after scraping. Thus, mitotic and amitotic cell division is an integral part of the posttraumatic regeneration process of the corneal endothelium of cats. PMID- 2597073 TI - The evolution of salmon-patch hemorrhages in sickle cell retinopathy. PMID- 2597072 TI - Barbiturates protect retinal cells from hypoxia in cell culture. AB - A culture system was used to screen for drugs that can protect mammalian retinal cells from damage induced by hypoxia. Using a special incubator, cultures could be made hypoxic for defined periods. Phase contrast photomicroscopy facilitated comparison of retinal cells before hypoxia and 1 to 2 days after hypoxia. Using 2 to 3-week-old cultures, certain glutamate antagonists, anesthetics, calcium blockers, and thiopental sodium were screened for their effect in protecting cells from hypoxia. The most remarkable effect was noted with thiopental. Quantitative measurements showed a significant increase in the percent of cells surviving after exposure to hypoxia in the presence of 100 mumol/L of thiopental sodium compared with control hypoxic cultures--82% vs 59% at 48 hours. A dose response curve demonstrated maximal effect at 50 mumol/L of thiopental sodium, with toxic effects noted at 200 mumol/L of thiopental sodium. Our results show that thiopental reduces hypoxia-induced damage to retinal cells in culture. PMID- 2597075 TI - A new retractable micromagnet for intraocular foreign body removal. AB - We have developed a new, self-contained, small-gauge, permanent, rare-earth magnet for use in conjunction with pars plana vitrectomy in the treatment of selected magnetic intraocular foreign bodies. This magnet allows controlled grasping and releasing of the foreign body by the surgeon, thus increasing surgical control in magnetic intraocular foreign body removal. PMID- 2597074 TI - Conjunctival flap-cosmetic shell-ptosis procedure. Treatment of blepharoptosis in severe keratopathy. AB - The correction of marked blepharoptosis in patients with severe or potential keratopathy will worsen the keratopathy and possibly lead to the complications of corneal ulceration and endophthalmitis. The conjunctival flap--cosmetic shell- ptosis procedure is well suited to this difficult management problem. Patients are initially treated with a conjunctival flap to protect their cornea. Subsequently they are fit with a cosmetic shell, and finally they undergo surgery to correct their ptosis. This three-stage procedure has produced excellent cosmetic and functional results in two patients, one of whom had ptosis and severe radiation-induced keratopathy following the treatment of a rhabdomyosarcoma; the other patient had severe ptosis associated with lack of corneal sensation and orbicularis function following removal of a cerebral meningioma. PMID- 2597076 TI - Hygiene factors and increased risk of trachoma in central Tanzania. AB - Trachoma remains the major infectious cause of blindness in many developing areas, especially where hygiene is poor. The practices and behaviors associated with an increased risk of trachoma were studied in central Tanzania, where a stratified random cluster sample of 8409 people was examined. Data were collected on family and individual characteristics and behaviors and on trachoma status. Overall, 60% of the children aged 1 to 7 years had active inflammatory trachoma, and 10% of those aged 60 years or older had trichiasis. Regression analysis showed that active inflammatory trachoma in children was associated with the characteristics of the more traditional families and several measures of poor personal hygiene. Two important risk factors for severe inflammatory trachoma were poor facial cleanliness in children (odds ratio of 1.7 [1.17, 2.50]) and household fly density (odds ratio of 1.63 [1.17, 2.29]). Both factors are potentially amenable to intervention. These data suggest that an intervention strategy aimed at these hygiene measures would provide an effective method of controlling trachoma in this region, and a similar approach may be useful in other areas. PMID- 2597077 TI - Neuropeptides in intact and denervated tympanic membranes. An immunohistofluorescence study in the rat. AB - The distribution and origin of peptide-containing and sympathetic nerve fibers were studied in the tympanic membrane of rats with intact innervation, and in rats following sympathectomy, vagotomy, or capsaicin treatment. Nerve fibers showing substance-P-like immunoreactivity (SP-LI), calcitonin gene-related peptide (CGRP)-LI, vasoactive intestinal polypeptide (VIP)-LI, enkephalin-LI, neuropeptide Y (NPY)-LI and tyrosine hydroxylase (TH)-LI were detected along blood vessels in the pars flaccida, the external auditory canal and in the fibrocartilaginous ring of the pars tensa. In the pars flaccida there were numerous fibers demonstrating SP-LI and CGRP-LI, while there were few such fibers in the pars tensa. In both portions of the tympanic membrane these fibers were present within and beneath the keratinized stratified squamous epithelium. In the pars flaccida, nerve fibers showing SP-LI and CGRP-LI were also seen near mast cells. Sympathectomy led to a loss of nerve fibers showing TH-LI and NPY-LI, whereas the other peptide-containing nerve fibers remained unaffected. Vagotomy did not reduce the immunoreactivity for any of the neuropeptides studied. Capsaicin treatment caused a reduction in nerve fibers displaying SP-LI and CGRP LI. The abundance of nerve fibers showing SP-LI and CGRP-LI in the keratinized squamous epithelium indicates that the tympanic membrane is richly supplied with sensory nerves. The localization of nerve fibers exhibiting these latter substances in the vicinity of mast cells in the pars flaccida suggests that this part of the tympanic membrane is a site where neurogenic inflammation occurs. PMID- 2597078 TI - Controlled hypotension during anesthesia for otologic operations. An ultrastructural study of the brain in an experimental animal model. AB - We have studied the fine structure of the cerebral cortex, the cerebellar cortex, the thalamus, the caudate nucleus, the amygdala, the putamen, the vestibular nuclei, the substantia nigra, the hippocampus and the centrum semiovale in a canine model following 20 min controlled hypotension by the administration of sodium nitroprusside. The neurons and the astrocytes of all structures were intact morphologically. The synapses in the cerebral and cerebellar cortex were all unremarkable. Sensitive areas such as the molecular layer of the cerebellum did not demonstrate any ultrastructural alterations. We believe that carefully controlled sodium-nitroprusside-induced hypotension might be applied in middle ear microsurgery in otherwise healthy patients as an effective and innocuous method without causing any anoxic insult to sensitive areas of the central nervous system. PMID- 2597079 TI - The effect of alcohol on the vestibulo-ocular reflex and gaze regulation. AB - To clarify the effect of the temporary decline in cerebellar function on the vestibulo-ocular reflex (VOR) and gaze functions, we examined 12 normal adults under passive rotations before and after they drank alcohol at dosages of 0.43 and 0.65 g/kg. Whereas spatial gaze fixation was maintained accurately with 0.65 g/kg administration (0.06% blood alcohol level), gaze fixation on a head-fixed target and smooth pursuit were impaired by the higher dosage of 0.43 g/kg (0.03% blood alcohol). The magnitude of the alteration in the VOR gain after drinking was correlated significantly with the VOR gain before drinking: while small values were enhanced by drinking, large values were suppressed. The present study indicates that the VOR in the dark is regulated by the balance between the amplifying and suppressing forces controlled by the cerebellum. PMID- 2597080 TI - Measurement of regional cerebral blood flow and accentuation of the primary auditory cortex with single photon emission computed tomography. AB - Conventional brain scanning uses polar tracers which do not penetrate the normal blood-brain barrier. Radiolabeled amines like 123-iodoamphetamine (IMP) cross the barrier to inhibit serotonin and norepinephrine in synaptosomes. Studies of cerebral perfusion and function seem to be successful with such labeling. We advance the hypothesis for an increased IMP uptake in the stimulated primary auditory cortex. The method of single photon emission computed tomography (SPECT) is described. We have also been able to demonstrate marking of the primary auditory cortex by an increased amphetamine input in 6 out of 15 cases during stimulation by white noise. PMID- 2597081 TI - The effects of anesthesia of the tympanic membrane on eustachian tube function. AB - In our previous histological studies of the tympanic membrane, we reported the presence of encapsulated nerve corpuscles that are capable of detecting middle ear pressure. Based on these findings, the relation between sensory receptors in the tympanic membrane and tubal function was examined in a clinical study. Tubal function was tested during Valsalva maneuvers and its active equilibration. Function was recorded as a change of the static compliance of the tympanic membrane on an otoadmittance meter. To paralyze the sensory receptors in the tympanic membrane, iontophoresis was used to induce anesthesia of the drum. Forty ears of 20 subjects were tested. All ears were able to equalize positive middle ear pressure without or with a single swallowing. After anesthesia, 13 ears needed more than two swallows and 4 ears failed to equalize middle ear pressure in spite of repeated swallowings. As eustachian tube function changed following anesthesia of the tympanic membranes, a neural connection between sensory receptors in the tympanic membrane and tubal muscles is suggested. PMID- 2597082 TI - Treatment of hemangiomas of the face with magnesium seeds. AB - Various conservative and surgical procedures are available for the management of aggressive hemangiomas in infancy and childhood. One of them is magnesium seeding, a treatment modality developed more than 90 years ago but neglected for a long time. The technique consists of implanting 0.5- to 1-mm-thick wires of 99.8% pure magnesium into the tumor mass. During repeated courses oxidation of the metal results in fibrosis and cicatricial transformation of the tumor. Indications, technique and results are discussed. PMID- 2597083 TI - Hemophilus influenzae adherence to and absorption from the nasal mucosa of guinea pigs. AB - The adherence to and the absorption from nasal mucosal epithelium of type b and non-typeable strains of Hemophilus influenzae were studied in guinea pigs. H. influenzae bacteria were administered to the nose as 4 x 10(7) organisms in 1.0 ml saline. The outer membrane vesicles (OMV) of H. influenzae were used in the absorption study. Scanning electron microscopic studies showed that H. influenzae cells attached to both ciliated and non-ciliated cells of the nasal mucosa. Histological studies showed that OMV were absorbed through the nasal mucosa, mainly from ciliated cells. Further, penetration of OMV through the nasal mucosa of immunized animals was reduced when compared with that of non-immunized ones. PMID- 2597084 TI - Rhabdomyoma of the larynx recurring after 12 years: immunocytochemistry and differential diagnosis. AB - Rhabdomyoma is a rare tumor of skeletal muscle origin which can occur in different localizations. The head and neck region is a site of predilection for the adult type. Its absolutely benign behavior makes correct diagnosis crucial. In this study, a case of an extracardiac rhabdomyoma of the larynx was found to recur 12 years after initial treatment. Following its surgical removal, histology showed typical patterns of an adult type of rhabdomyoma with focal cross striations. Immunocytochemically, all applied muscular markers were positive. Electron microscopy revealed muscular filaments with cross-striations and glycogen granules. These findings showed that immunocytochemistry plays an important role in differential diagnosis and the need for possible further treatment. PMID- 2597085 TI - Analgesia and anesthesia during labor in Japan and developed countries. AB - Analgesia and anesthesia during labor were surveyed by the use of a questionnaire sent to university hospitals in USA, UK, France, FRG, GDR, Japan, and also other types of institutions in Japan. A rather negative attitude toward analgesia and anesthesia during labor was encountered less often in Japan than in USA, UK, and FRG, but the actual frequency of use was much less in Japan. Narcotics and/or tranquilizers were most frequently used in the first stage of labor. The only exception was France where lumbar epidural anesthesia was actually used as a method of choice at 70% of the institutions. Lumbar epidural anesthesia or some other regional block was the method of choice in the second stage except in UK where inhalation of nitrous oxide was the method of choice at 48% of the institutions. Augmentation of labor was much more frequent and the number of annual deliveries were much less in Japan. Higher C-section rate was seen in USA. PMID- 2597086 TI - Uterine malignancy developing after long term use of IUCD additional report of 2 cases: endometrial stromal sarcoma and leiomyosarcoma. AB - In our 2 previous papers published in this Journal, we had 5 cases of uterine malignancies developing after long term use of IUCD's. In the present paper 2 cases of such association are to be added. One case ATH with right adnexectomy was performed for persisting vaginal bleeding after 22 years of Lippes Loop application and recurrence 8 years after the first operation. Pathological diagnosis is endometrial stromal sarcoma. The other case is a leiomyosarcoma developing after 25 years of Lippes Loop application. Although no cause and effect relationship between IUCD use and uterine malignancy in human beings has been proved, the increase in such cases suggests to us that long term application should be avoided, particularly in view of the positive animal experiments. The successive detection of such cases in a relatively short period of time prompts us to make further studies to gain a deeper insight into such associations. PMID- 2597087 TI - Routine gamete intrafallopian transfer (GIFT): a highly successful option for treatment of non-tubal infertility. AB - Gamete intrafallopian transfer (GIFT) is increasingly accepted as a realistic alternative to in vitro fertilization (IVF), or intrauterine insemination (IUI) for treatment of non-tubal infertility. The lack of information on fertilization capacity of the gametes, the greater cost relative to IUI, and the partly unsubstantiated claims of higher success rates, caused us some concern with the readiness with which GIFT had been accepted as a standard infertility treatment. So we undertook a provisional GIFT programme with these considerations in mind, and we report on the first 91 GIFT cycles performed in our clinic. Sixty of the patients (62 cycles) treated suffered from idiopathic infertility, 12 from minimal endometriosis, 9 from male factor infertility, and 8 from ovulatory dysfunction. An initial clinical pregnancy rate of 41% (38/91) was achieved; pregnancy loss was 23% (9/38), giving a continuing pregnancy rate of 32% (29/91). Given this undeniably encouraging result, and the potential for diagnostic IVF, embryo freezing, and ovum donation with surplus oocytes collected from this GIFT programme, we now have adopted GIFT permanently as a treatment to complement our IVF and IUI programmes. PMID- 2597088 TI - Clinical significance of a solid-phase immunoradiometrical assay for sialyl SSEA 1 antigen in obstetrics and gynecology. AB - The clinical usefulness of sialyl SSEA-1 antigen was evaluated in obstetrics and gynecology. Serum levels of sialyl SSEA-1 were measured in patients with benign or malignant gynecologic diseases, and in normal pregnant women. Moreover, in 10 cases of full term delivery, samples of maternal sera immediately prior to delivery, soon after delivery and 5-day-puerperium, cord sera from the umbilical artery and vein, and amniotic fluid were taken to measure its concentration. During the course of pregnancy, serum SSEA-1 levels were within the normal range (below 38 U/ml), showing no significant correlation with gestational weeks. Of patients with gynecologic diseases, those with malignant ovarian neoplasms, uterine cervical carcinoma and benign ovarian neoplasms exhibited elevated (over 38 U/ml) levels in 26%, 15% and 6% of all cases, respectively. In cases of full term delivery, the concentrations of sialyl SSEA-1 in the maternal and cord sera were within the normal range. Concentrations were extremely high, however, in the amniotic fluid. PMID- 2597089 TI - Merkel cell carcinoma of the vulva: a case report. AB - The clinical and pathologic findings of Merkel cell carcinoma of the vulva were reported. The light microscopic findings of sheets of small, uniform cells were consistent with a diagnosis of neuroendocrine tumor. The electron microscopic characteristics revealed membrane-bound secretory granules, confirmed the diagnosis of Merkel cell carcinoma. Regional lymphnode metastases were present at the time of initial surgery and the adjunctive radiotherapy was also given. This case was unusual because Merkel cell carcinoma was usually found on the face, extremities and buttocks. PMID- 2597090 TI - The attitudes of doctors and students towards a genetic service in an Asian country: Sri Lanka. AB - A study comparing the views on the acceptance of a genetic service of 302 doctors and 143 final year medical students from Colombo, Sri Lanka, showed both groups have strong positive views on the provision and use of genetic counselling, prenatal diagnosis of genetic disorders and therapeutic abortion. The students responded with greater restraint possibly due to being a younger cohort with less clinical experience. Both groups, however, showed little support for the use of prenatal diagnosis purely to determine fetal sex. PMID- 2597091 TI - Tubal cyst following tubal sterilization: a delayed complication. AB - Clinical pictures and histopathological findings in 15 patients of tubal cyst following tubal sterilization were analyzed. The interval between tubal sterilization and occurrence of tubal cyst was 10 years (ranged from 4 to 21 years). Clinically 8 cases (53%) suffered from lower abdominal pain, 5 cases (33%) from hypermenorrhea coexistent with uterine myoma and 2 cases (13%) from irregular menstruation. Five out of 9 patients with ultrasound examination were suspected to have tubal cyst before operation. The size of tubal cyst ranged from 1.5 to 9.0 cm in diameter with mean 3.4 cm. Eleven were unilateral and 4 were bilateral. Histologically they showed flattened mucosal epithelial cells with absence of epithelial plica, compression atrophy of muscular layer, suture stitch or granuloma and intact fimbria with clear serous fluid. Thus, the differential diagnosis of adnexal cyst in patients with a past history of tubal sterilization should include tubal cyst. PMID- 2597092 TI - Hepatocellular lipofuscin in pre-eclampsia. AB - Thirty liver specimens from 30 pre-eclamptic women with and without liver dysfunction were examined for the amount of lipofuscin pigment deposited. The amount of hepatic lipofuscin correlated positively with plasma urate concentrations. This finding may indicate an involvement of oxygen-free radicals and xanthine oxidase in the pathophysiology of pre-eclampsia. PMID- 2597094 TI - A rise in the biologically active LH: immunologically active LH (B/I) ratio during the normal luteal phase. AB - Biologically active (bio) LH concentrations and immunologically active (immuno) LH concentrations were measured in integrated hourly blood samples collected over 24 h study periods (n = 27) and in 5 min blood samples collected over 2 h study periods (n = 21) during different stages of the menstrual cycle in a group of regularly cyclic women. Episodic fluctuations were seen in both the bio LH and immuno LH concentrations in hourly as well as in 5 min data series. However, there was no consistent correlation between episodes of bio LH and immuno LH. Mean B/I ratio over the 24 h study periods as well as over the 2 h study periods were significantly higher during the luteal phase than during either the follicular phase (p less than 0.002) or the mid cycle (p less than 0.02). PMID- 2597093 TI - Metabolism of amniotic fluid dopamine by fetal membranes. AB - The concentrations of L-dopa, three catecholamines and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured both in the amniotic fluid and the fetal urine obtained at term elective cesarean section, using high performance liquid chromatography with electrochemical detection. Dopamine was the major compound in the fetal urine, while DOPAC predominated in the amniotic fluid. Monoamine oxidase (MAO) activity was detected in the fetal membranes by the method of Wurthman and Axelrod. MAO activities in the amnion, chorion and decidua were 0.023 +/- 0.003, 0.180 +/- 0.05 and 2.69 +/- 0.66 nmol/mg protein/min (mean +/- SE), respectively. Incubation experiments, using fetal membranes with human amniotic fluid, demonstrated that dopamine in amniotic fluid was metabolized to DOPAC by fetal membranes. Additional incubation experiments with pargyline, a MAO inhibitor, showed that it strongly inhibited the conversion of dopamine into DOPAC. These results suggest that the dopamine in amniotic fluid was metabolized to DOPAC by MAO in the fetal membranes. This mechanism may regulate the dopamine concentration in amniotic fluid. PMID- 2597095 TI - Influence of stimulus intensity on AEP components in the 80- to 200-millisecond latency range. AB - The influence of the intensity of passively perceived 1-kHz tones on the latencies and amplitudes of AEP components in the 80- to 200-ms latency range recorded from frontal, central and temporal electrode locations was investigated in healthy adult subjects. At stimulus intensities from 30 to 70 dB SL the latencies of the frontally and centrally recorded N100 and P175 waves decreased, their amplitudes increased. At stimulus intensities from 70 to 90 dB the latencies of N100 and P175 increased, N100 amplitude declined and P175 amplitude increased at a slower rate than between 30 and 70 dB. The latency of the N140 wave recorded at temporal electrode locations decreased markedly with increasing stimulus intensity. PMID- 2597096 TI - Cerebral magnetic responses to noise bursts and pauses of different durations. AB - We compared magnetic-evoked responses of human auditory cortex to short (5, 10, 20, 40, 80 and 160 ms) noise bursts and to pauses of identical durations in continuous noise. Onsets of both stimuli evoked responses with the most prominent deflection (N100m) peaking at about 100 ms. Both field maps could be explained by current dipoles, which agree with activity at the supratemporal cortex at slightly different locations. At the shortest 5-ms duration the noise bursts evoked a clear N100m whereas pauses elicited very low-amplitude responses or no response at all. For both stimuli, N100m increased in amplitude when the stimulus duration was increased from 5 up to 20-40 ms. The latencies were 10-20 ms longer for pauses than noise bursts with the longest latencies at the shortest stimulus durations. The differences in amplitudes and latencies as a function of stimulus duration and the slightly different source areas indicate that the generators of the on- and off-responses are not identical. PMID- 2597097 TI - Academic surgery and the Bachelor of Medical Science degree. PMID- 2597098 TI - Education for clinical science: experience in Australia and England. PMID- 2597099 TI - Incidence and significance of pneumoperitoneum after inguinal herniorrhaphy. AB - Previous studies have shown pneumoperitoneum either to be extremely rare or to not occur after inguinal herniorrhaphy, and that its presence signifies a serious intra-abdominal complication. A prospective study has been carried out to consider the incidence and significance of pneumoperitoneum after herniorrhaphy for indirect inguinal hernias. In a 1-year period, 100 patients were studied. Pneumoperitoneum was detected in six patients. In five patients, the amount of free gas was minimal and was reabsorbed after 48 h. The pneumoperitoneum was large and of increasing amount in one patient. Faecal fistula developed 7 days after operation due to an injury from the hernial repair to the sigmoid colon. The result of this study suggested that detectable pneumoperitoneum of small amount may be present after inguinal herniorrhaphy and, if it persists for longer than 48 h, the presence of a perforated viscus should be considered. PMID- 2597100 TI - Cyclical rectal bleeding in colorectal endometriosis. AB - Three case reports of cyclical rectal bleeding in endometriosis affecting rectum and sigmoid colon emphasize the close relationship between such cyclical bleeding and intestinal endometriosis. The cause of bleeding, however, is still unclear. The predilection of endometriotic deposits for the outer layers of the bowel wall suggests that mucosal involvement is not a prerequisite for rectal bleeding. The frequent absence of identifiable intramural haemorrhage casts doubt on the premise that intestinal endometriotic deposits 'menstruate'. The cause may simply be a transient tear in normal mucosa due to swelling of an underlying endometriotic deposit at the time of menstruation. PMID- 2597102 TI - Complications associated with penile implants used to treat impotence. AB - The complications associated with a variety of penile prostheses used in the treatment of 302 men with erectile dysfunction are described. Infection of the prostheses resulted in their removal from 11 patients (3.6%), antibiotic therapy and replacement in five men. Mechanical failures required reoperation in 43 men (14.2%); however, recent advances in prosthesis design have reduced this type of malfunction. Adverse psychological reactions prompted removal of the prostheses from two men. Despite these complications, this surgery is remarkably effective. PMID- 2597101 TI - Aetiology of branchial cysts. AB - The aetiology of branchial cysts is unknown. It is possible that they arise by more than one mechanism. The major theories are that they originate either from the branchial apparatus or from lymphoid tissues. A retrospective review was conducted of 61 cases occurring over a recent 14-year period. Eighty-five percent were diagnosed after the age of 10 years, 80% occurred in the 'classical' position, 80% had a squamous epithelial lining and 87% had lymphoid tissue in the wall. The clinical and histological features strongly support the lymphoid aetiology theory for the majority of branchial cysts. PMID- 2597103 TI - Non-surgical management of phimosis. AB - Management of phimosis without operation is a possible alternative option for balanitis problems in certain circumstances. PMID- 2597104 TI - Spontaneous rupture of hepatic epithelioid haemangio-endothelioma. AB - A 69 year old man presented with haemoperitoneum due to spontaneous rupture of a hepatic epithelioid haemangio-endothelioma. The tumour was found by ultrasound and coeliac angiogram to be locally advanced, involving both lobes of the liver. The bleeding was stopped by transcatheter arterial embolization. The diagnosis was established 4 weeks later by a Trucut biopsy under ultrasound guidance. The patient refused further treatment by radiation and chemotherapy, so he was observed closely. Chest radiography carried out 3 months later revealed multiple pulmonary secondaries. Despite his disseminated disease, he was well and enjoying a normal active life 4 months after embolization. PMID- 2597105 TI - The fuel of the spleen. Studies using a new method for perfusing the rat spleen with whole blood. AB - 1. An improved rat spleen perfusion is described incorporating a method of defibrination which avoids the use of heparin and enables the spleen to be perfused with rat blood for several hours at a haematocrit of 40% and for 12 h or more at a haematocrit of 20%. 2. Glucose oxidation accounted for 11.6% of the total oxygen consumption but this represented only 8% of total glucose uptake, which was largely converted to lactate and released into the perfusate. However, significant amounts of lactate were oxidized. These results can be explained by the presence of at least two cell populations, one emphasizing the anaerobic oxidation of glucose and the other aerobic metabolism, particularly of lactate. 3. Non-esterified fatty acid and 3-hydroxybutyrate, when available at physiological concentrations, were shown to be major oxidative fuels of the spleen. 4. Chylomicron triacylglycerol was hydrolysed readily and taken up, but not oxidized extensively. PMID- 2597106 TI - Effects of hypothyroidism and hyperthyroidism on GDP binding to brown-adipocyte mitochondria from rats. AB - 1. Rats were made hypothyroid by giving them a low-iodine diet with propylthiouracil for 4 weeks, or were made hyperthyroid by injection with tri iodothyronine (T3) over a 3-day period. 2. Brown adipocytes were isolated from the interscapular depots of these animals or from their euthyroid controls, followed by isolation of mitochondria from the cells. 3. Relative to cell DNA content, hypothyroidism decreased the maximum binding (Bmax.) of [3H]GDP to mitochondria by 50%. T3 treatment increased binding by 37%. 4. These findings, which are discussed in relation to previously observed changes in brown adipose tissue after alteration of thyroid status, suggest that mitochondrial uncoupling for thermogenesis is less or more effective in hypothyroidism or hyperthyroidism respectively. PMID- 2597107 TI - Prolonged high intracellular free calcium concentrations induced by ATP are not immediately cytotoxic in isolated rat hepatocytes. Changes in biochemical parameters implicated in cell toxicity. AB - Isolated rat hepatocytes were incubated with ATP to induce high intracellular free Ca2+ concentrations as determined with the Quin-2 method. Immediately after addition of ATP, the intracellular concentration of Ca2+ rose from 200 nM to more than 2.5 microM. It stayed at this value during the first 1/2 h; the rise was absolutely dependent on extracellular Ca2+. After the first 1/2 h the Ca2+ concentration decreased to 1-2 microM (5-10 times the control value). These high intracellular free Ca2+ concentrations did not lead to an immediate loss of cell viability. Only after 2 h of incubation a substantial number of cells lost viability. This was preceded by a decrease in cellular NADH (greater than 40%) and accompanied by a sharp increase in the intracellular Ca2+ concentration. Under these conditions the NADPH concentration was not affected. Cellular GSH was decreased to 30% of the initial value, but no lipid peroxidation or protein-thiol depletion was observed. Intracellular ATP, ADP and AMP were increased in the presence of extracellular ATP. Ca2+-dependent proteases seemed not to be involved in cell death. These observations are consistent with a collapse of mitochondrial functions as a final trigger of cell death. PMID- 2597108 TI - Human serum amyloid A protein. Behaviour in aqueous and urea-containing solutions and antibody production. AB - Human serum amyloid A protein (apo-SAA) can be prepared by gel filtration of delipidated acute-phase high-density lipoprotein in the presence of urea. The resultant apo-SAA is soluble (greater than 90% solubility) in a wide range of buffer solutions, with all of the six major isoforms of apo-SAA being equally soluble. In urea-containing solutions the isoforms behave qualitatively differently in various urea concentrations, probably reflecting subtle primary structure variations. The higher-pI isoforms are only completely unfolded at greater than 7 M-urea. By immunizing with apo-SAA adsorbed to acid-treated bacteria (Salmonella minnesota R595), high-titre antibodies can easily be elicited in rabbits. PMID- 2597109 TI - Extracellular nucleotides stimulate receptor-mediated calcium mobilization and inositol phosphate production in human fibroblasts. AB - In human skin fibroblasts, low concentrations of extracellular ATP stimulated 45Ca2+ efflux from a slow-turnover intracellular pool, accompanied by inositol phosphate generation. These effects of ATP were not due to a generalized increase in plasma-membrane permeability. The EC50 (concn. giving 50% stimulation) for ATP was dependent on Ca2+ and Mg2+ concentrations in a manner which indicates that a form of ATP uncomplexed with bivalent cations is the active species. The rank order of potency of nucleotides was: ATP = UTP greater than adenosine 5'-[gamma thio]triphosphate greater than ITP greater than ADP greater than UDP greater than other nucleoside triphosphates. Adenosine 5'-[alpha beta-methylene]triphosphate, adenosine 5'-[beta gamma-methylene]triphosphate and 2-methylthio-ATP were inactive. Thus the nucleotide specificity of this receptor is different from that of previously characterized P2 purinoceptors. Nucleotide-stimulated 45Ca2+ mobilization and inositol phosphate production were markedly inhibited by phorbol ester, and partially inhibited by pertussis-toxin pretreatment. These findings suggest that the coupling of nucleotide receptor to phospholipase C is mediated both by a pertussis-toxin-sensitive G-protein and by a pertussis-toxin insensitive mechanism. PMID- 2597110 TI - A simplified assay for the enzyme responsible for the attachment of myristic acid to the N-terminal glycine residue of proteins, myristoyl-CoA: glycylpeptide N myristoyltransferase. AB - A greatly simplified assay for myristoyl-CoA:glycylpeptide N-myristoyltransferase (NMT) activity is described. The assay is based on the differential solubility of the acyl-peptides produced as a consequence of the NMT activity and yields results comparable with those obtained with the original assay described by Towler & Glaser [(1986) Proc. Natl. Acad. Sci. U.S.A. 83, 2812-2816], which requires h.p.l.c. to determine the production of the acyl-peptides. The use of the revised assay in the preliminary steps of the purification of rat brain NMT is described, and its use in determining the fatty acid-specificity of the enzyme is illustrated. The results are shown to be comparable with those obtained with the h.p.l.c.-based assay. PMID- 2597111 TI - Differential induction of class alpha glutathione S-transferases in mouse liver by the anticarcinogenic antioxidant butylated hydroxyanisole. Purification and characterization of glutathione S-transferase Ya1Ya1. AB - A novel cytosolic Alpha class glutathione S-transferase (GST) that is not normally expressed in mouse liver was found to be markedly induced (at least 20 fold) by the anti-carcinogenic compound butylated hydroxyanisole. This enzyme (designated GST Ya1 Ya1) did not bind to either the S-hexylglutathione-Sepharose or the glutathione-Sepharose affinity matrices, and purification was achieved by using bromosulphophthalein-glutathione-Sepharose. The purified isoenzyme, which comprises subunits of Mr 25,600, was characterized, and its catalytic, electrophoretic, immunochemical and structural properties are documented. GST Ya1 Ya1 was shown to be distinct from the Alpha class GST that is expressed in normal mouse liver and is composed of 25,800-Mr subunits; the Alpha class isoenzyme that is constitutively expressed in the liver is now designated GST Ya3 Ya3. Hepatic concentrations of GST Ya3 Ya3 were not significantly affected when mice were treated with butylated hydroxyanisole. Both Pi class GST (subunit Mr 24,800) and Mu class GST (subunit Mr 26,400) from female mouse liver were induced by dietary butylated hydroxyanisole. By contrast, hepatic concentrations of microsomal GST (subunit Mr 17,300) were unaffected. PMID- 2597112 TI - Chemical synthesis of all-trans-[11-3H]retinoyl beta-glucuronide and its metabolism in rats in vivo. AB - All-trans-[11-3H]retinoyl beta-glucuronide (RAG) was synthesized in a single step from all-trans-[11-3H]retinoyl fluoride, with a 24% yield. After its intraperitoneal injection into rats, RAG was detected in the blood, liver, intestine and kidney during the following 24 h period. Although the concentration of radiolabelled metabolites decreased with time, RAG predominated at nearly all times in nearly all tissues. Small amounts of retinoic acid (RA) were also universally present, together with unidentified polar metabolites and small amounts of non-polar esters of RA. The major excretion products of RAG in faeces and urine were RA and polar metabolites. Thus RAG, although converted in part to RA in vivo, persists as a major component in blood and tissues for at least 24 h. These observations support the concept that the retinoid beta-glucuronides might serve a physiologically significant role in the function of vitamin A. PMID- 2597113 TI - Inhibition of apolipoprotein B net synthesis and secretion from cultured rat hepatocytes by the calcium-channel blocker diltiazem. AB - 1. The effect of the Ca2+-channel blocker diltiazem on hepatic apolipoprotein B (apo B) synthesis and secretion was studied in 12-18 h cultures of collagenase dispersed rat hepatocytes. 2. The presence of diltiazem in the medium decreased apo B secretion by hepatocytes in a concentration-dependent manner. At 25 microM, diltiazem inhibited apo B secretion by approx. 36%, but there was no evidence of intracellular accumulation of apo B. 3. The inhibition of apo B secretion by hepatocytes was significantly correlated with cell-associated diltiazem (r = 0.72, P less than 0.01). 4. The rate of apo B secretion remained linear over 16 h even in the presence of 50 microM-diltiazem. 5. At diltiazem concentrations in the medium which were inhibitory for apo B secretion, [14C]acetate incorporation into cellular lipids and [35S]methionine incorporation into protein were enhanced. 6. Diltiazem inhibited the secretion of the apo B variants with a preferential inhibition of the higher-molecular-mass form of apo B (apo BH) over the lower-molecular-mass form (apo BL) at diltiazem concentrations in the medium greater than 25 microM. 7. Together, these results suggest that Ca2+ may play an important role in the synthesis and secretion of apo B-containing lipoproteins. PMID- 2597114 TI - Effects of thiolation on the immunoreactivity of the ribosome-inactivating protein gelonin. AB - Gelonin purified from the seeds of Gelonium multiflorum using cation-exchange and gel-filtration chromatography was characterized for its purity, homogeneity and Mr by reverse-phase h.p.l.c. and SDS/polyacrylamide-gel electrophoresis analysis and judged to be 98% pure. As the cross-linking agent N-succinimidyl-3-(2 pyridyldithio)propionate (SPDP) has been used for linking gelonin via its epsilon NH2 group to its carrier antibodies or hormones for immunotoxin or hormonotoxin respectively, an attempt was made to study the effect of this modification of gelonin on its immunoreactivity. A radioimmunoassay was developed for this purpose. By sequential modification, four categories of amino group modifications on immunoreactivity were observed. Even one or two modifications, representing one-twentieth to one-tenth of available epsilon-NH2 groups in the protein caused about 75% loss in immunoreactivity, with additional reactions contributing to further deteriorations. By using a gelonin radioimmunoassay, the immunoreactivity of gelonin in three hormonotoxins was determined with gelonin and modified gelonin as standards. The gelonin equivalent in our hormonotoxins was in agreement with the values determined by spectrophotometric and gel electrophoresis methods. As the immunoreactivity of gelonin-SPDP was not further altered after conjugation to its carrier protein ovine lutropin, a specific radioimmunoassay of gelonin could be used to evaluate the molar ratio of the conjugates prepared by using SPDP as cross-linker and gelonin-SPDP as a standard. PMID- 2597115 TI - Purification and characterization of a digestive cysteine proteinase from the American lobster (Homarus americanus). AB - A new cysteine proteinase was isolated from the digestive juice of the American lobster (Homarus americanus). The enzyme was purified by a combination of affinity and ion-exchange chromatography and gel filtration. The cysteine proteinase accounted for 80% of the proteolytic activity in the lumen of the hepatopancreas. The most potent heavy-metal inhibitors were Hg, Cu, and Ag ions. Inhibition by organic proteinase inhibitors, including E-64 [L-trans epoxysuccinyl-leucylamido-(4-guanidino)butane] and activation of the enzyme by 2 mercaptoethanol and dithiothreitol are characteristic of cysteine proteinases. Several similarities to papain are noted and include the N-terminal sequence, of which 22 of the first 28 amino acids are identical. Some notable differences are the higher Mr of 28,000 compared with 23,350 for papain, and the low isoelectric point (pI 4.5) of the lobster enzyme. The effects of pH and temperature on catalytic activity of the lobster proteinase were studied with benzyloxycarbonylalanine p-nitrophenyl ester as the substrate. The kcat./Km value was effectively temperature-independent between 10 and 60 degrees C. The pH activity profile for the lobster enzyme revealed four apparent protonation states, of which only two are active. PMID- 2597116 TI - Rapid purification of pig heart NAD+-isocitrate dehydrogenase. Studies on the regulation of activity by Ca2+, adenine nucleotides, Mg2+ and other metal ions. AB - 1. A new procedure for purifying pig heart NAD+-isocitrate dehydrogenase from mitochondrial extracts has been developed. This relies on the use of f.p.l.c. techniques and exploits the hydrophobic properties of the gel-filtration medium Superose 6 at high ionic strength. A 300-fold purification to apparent homogeneity is achieved within 5 h and with a yield of greater than 20%. 2. The enzyme had an apparent native molecular mass on gel filtration of 320 kDa. In agreement with previous studies [Ramachandran & Colman (1980) J. Biol. Chem. 255, 8859-8864], three subunits (all close to 38 kDa) were separable by isoelectric focusing 3. This preparation was used to investigate the effects of adenine nucleotides, KCl and the required bivalent metal ions, Mg2+ and Mn2+, on the regulation of the enzyme by Ca2+. 4. In the presence of 1.5 mM-ADP, increasing the concentration of Mg2+ from 20 microM to 6.0 mM raised the concentration of Ca2+ required for half-maximal effect (K0.5 value) from 1.2 microM to 232 microM. Similarly, in the presence of 2.5 microM-Mn2+, a K0.5 value for Ca2+ of 3.3 microM was obtained, and this value was increased to 8.9 microM in the presence of 100 microM-Mn2+. In the presence of 1 mM-Mg2+ and 1.5 mM-ADP, the K0.5 value for Ca2+ was raised from 4.7 microM to 10 microM by 75 mM-KCl. PMID- 2597117 TI - The binding of Ca2+ ions to pig heart NAD+-isocitrate dehydrogenase and the 2 oxoglutarate dehydrogenase complex. AB - 1. The binding of Ca2+ ions to purified pig heart NAD+-isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase, freed of contaminating Ca2+ by parvalbumin/polyacrylamide chromatography, has been studied by flow dialysis and by the use of fura-2. 2. For the 2-oxoglutarate dehydrogenase complex, 3.5 mol of Ca2+-binding sites/mol of complex were apparent, with an apparent dissociation constant (Kd value) for Ca2+ of 2.0 microM. These values were little affected by Mg2+ ions, ADP or 2-oxoglutarate. 3. By contrast, binding of Ca2+ to NAD+ isocitrate dehydrogenase (Kd = 14 microM) required ADP, isocitrate and Mg2+ ions. The number of Ca2+-binding sites associated with NAD+-isocitrate dehydrogenase was then 0.9 mol/mol of tetrameric enzyme. 4. The 2-oxoglutarate dehydrogenase complex bound ADP (as ADP3-) to a group of tight-binding sites (Kd = 3.1 microM) with a stoichiometry, 3.3 mol/mol of complex, similar to that for the binding of Ca2+; a variable number of much weaker sites (Kd = 100 microM) for ADP3- was also apparent. PMID- 2597118 TI - Fish skeletal muscle contains a novel serine proteinase with an unusual subunit composition. AB - Proteinase I, an enzyme previously shown to be able to degrade contractile and cytoskeletal elements of white-croaker (Micropogon opercularis) myofibrils, was purified to apparent homogeneity by chromatography on DEAE-Sephacel, octyl Sepharose CL 4B and arginine-Sepharose 4B. Its Mr was determined to be 269,000 by Sephacryl S-300 gel filtration. Under denaturing conditions, the enzyme dissociated into two subunits with Mr 20,000 and 15,500, in a molar ratio of 1.8:1. Proteinase I showed a pH optimum of 8.5. The enzyme was strongly inhibited by several serine proteinase inhibitors, whereas inhibitors of the other types of proteinases did not affect, or only scarcely affected, its activity. Several N terminal-blocked 4-methyl-7-coumarylamide substrates having either arginine or lysine residues adjacent to the fluorogenic group were efficiently hydrolysed by the enzyme. These results indicate that proteinase I is a trypsin-like serine proteinase. The enzyme appears to be distinct from other proteinases previously described in skeletal muscle, and might be involved in the catabolism of myofibrillar proteins. PMID- 2597119 TI - Isolation, in the intact state, of the pterin molybdenum cofactor from xanthine oxidase. AB - A procedure is described for isolation of the pterin molybdenum cofactor, in the active molybdenum-containing state, starting from purified milk xanthine oxidase. The method depends on the use of anaerobic-glove-cabinet techniques and on working in aqueous solution, in the presence of 1 mM-Na2S2O4. SDS was used to denature the protein, followed by ion-exchange chromatography and gel filtration. The cofactor, obtained at concentrations up to 0.5-1.0 mM, was fully active in the nit-1 assay [Hawkes & Bray (1984) Biochem. J. 214, 481-493], with a specific activity of 22 nmol of NO2-/min per pg-atom of Mo (with 15% molybdate dependence). The Mr, determined by gel filtration, was about 610, consistent with the structure proposed by Kramer, Johnson, Ribeiro, Millington & Rajagopalan [(1987) J. Biol. Chem. 262, 16357-16363]. At pH 5.9, under anaerobic conditions, the cofactor was stable for at least 300 h at 20-25 degrees C. PMID- 2597120 TI - Desialylation of transferrin by liver endothelium is selective for its triantennary chain. AB - Liver endothelium can remove and transport the glycoprotein transferrin (TF). During this process the molecules are desialylated; however, in contrast with other such glycoproteins, for example caeruloplasmin, only half of transported TF is desialylated. To explore which component of TF is desialylated, we double labelled fully sialylated TF with [3H]sialic acid residues and a 125I-protein moiety. This was then 'chased' through purified liver endothelium in pulse-chase experiments. Endothelium-conditioned TF was fractionated on an RCA120 affinity column into sialylated and desialylated components. Each component was then re fractionated on a concanavalin A affinity column, which separates the glycoprotein according to the branching pattern of its glycan chain. The desialylated fraction was eluted only as a triantennary component, whereas the non-desialylated fraction consisted only of bi- and tetra-antennary chains. The significance of this selective desialylation of triantennary chain of TF in the subsequent metabolism of its iron content and its possible role in the pathogenesis of alcohol-induced hepatic siderosis are discussed. PMID- 2597121 TI - Killing of gram-negative bacteria by complement. Fractionation of cell membranes after complement C5b-9 deposition on to the surface of Salmonella minnesota Re595. AB - The effect of C5b-9 deposition on the envelope of target Gram-negative bacteria was studied. In order to understand the changes occurring after complement deposition on the bacterial surface, the preparation of Gram-negative bacterial membranes by different methods involving the osmotic lysis of spheroplasts was investigated. Subsequent fractionation of the outer membrane (OM) and cytoplasmic membrane (CM) by sucrose-density-gradient centrifugation showed differences in the membrane profiles obtained. The results indicate that optimum separation of OM and CM components requires effective digestion of DNA in the total membrane preparation before density-gradient fractionation. Salmonella minnesota Re595 carrying the intermediate complement complex C5b-7 (BC1-7) or C5b-8 (BC1-8) were efficiently killed upon incubation with purified C8 + C9 or C9 respectively. Human-alpha-thrombin-cleaved C9 (C9n), which is unable to form tubular poly(C9), was shown to be more effective at killing than native C9. By using an optimized system for the separation of OM and CM, it was found that, subsequent to lethal complement attack, the CM could not be recovered when C9 was used as the terminal complement component, but was recovered with reduced yield when C9n replaced C9. The results show that inability to recover the CM on sucrose density gradients after complement attack may not be a consequence of an essential membrane damage event required for complement-mediated killing of Gram-negative bacteria. PMID- 2597122 TI - Analysis of the water-soluble products of phosphatidylcholine breakdown by ion exchange chromatography. Bombesin and TPA (12-O-tetradecanoylphorbol 13-acetate) stimulate choline generation in Swiss 3T3 cells by a common mechanism. AB - A method for the rapid and quantitative separation of glycerophosphocholine, choline phosphate and choline upon ion-exchange columns is described. The method has been utilized to examine the stimulation of phosphatidylcholine breakdown in quiescent Swiss 3T3 cells in response to bombesin and 12-O-tetradecanoylphorbol 13-acetate (TPA). The stimulated generation of choline is shown to precede that of choline phosphate, with no effect upon glycerophosphocholine levels; but was attenuated in cells in which protein kinase C activity was down-regulated. The results thus suggest that stimulation of the cells with either bombesin or TPA activates phospholipase D-catalysed phosphatidylcholine breakdown by a common mechanism involving the activation of protein kinase C. PMID- 2597124 TI - Confirmation of D-aspartic acid in the novel dipeptide beta-aspartylglycine isolated from tissue extract of Aplysia kurodai. AB - A novel o-phthalaldehyde-reactive compound was found in the h.p.l.c. chromatogram of Aplysia kurodai extract. This compound was isolated by ion-exchange chromatography and preparative high-voltage paper electrophoresis. It was shown by optical-rotatory-dispersion spectrum and optical-resolution h.p.l.c. analysis that this compound consisted of equimolar amounts of D-aspartic acid and glycine. This compound resisted cleavage in the Edman reaction. This peptide was inferred to be beta-D-aspartylglycine, and this was confirmed by synthesis. beta-D Aspartylglycine was detected in all tissues of Aplysia kurodai, with especially high concentrations in body wall (skin and muscle) and gill. PMID- 2597123 TI - Phosphorylation of the tight-junction protein ZO-1 in two strains of Madin-Darby canine kidney cells which differ in transepithelial resistance. AB - A comparison was made of the phosphate content of the tight-junction-specific protein ZO-1 in two strains of Madin-Darby canine kidney cells which differ in transepithelial resistance, a parameter reflective of tight-junctional permeability. Analysis revealed that the ZO-1 from the low-resistance strain contained approximately twice as much phosphate as that from the high-resistance strain. PMID- 2597125 TI - Kinetic study of the irreversible thermal denaturation of Bacillus licheniformis alpha-amylase. AB - The irreversible thermal inactivation of Bacillus licheniformis alpha-amylase was studied. A two-step behaviour in the irreversible denaturation process was found. Our experimental results are consistent only with the two-step model and rule out the two-isoenzyme one. They suggest that the deactivation mechanism involves the existence of a temperature-dependent intermediate form. Therefore the enzyme could exist in a great number of active conformational states. We have shown that Ca2+ is necessary for the structural integrity of alpha-amylase. Indeed, dialysis against chelating agents leads to a reversible enzyme inactivation, though molecular sieving has no effect. Further, the key role of Ca2+ in the alpha amylase thermostability is reported. The stabilizing effect of Ca2+ is reflected by the decrease of the denaturation constants of both the native and the intermediate forms. Below 75 degrees C, in the presence of 5 mM-CaCl2, alpha amylase is completely thermostable. Neither other metal ions nor substrate have a positive effect on enzyme thermostability. The effect of temperature on the native enzyme and on one intermediate form was studied. Both forms exhibit the same optimum temperature. Identical activation parameters for the hydrolytic reaction catalysed by these two forms were found. PMID- 2597127 TI - Molybdenum nitrogenase of Azotobacter chroococcum. Tight binding of MgADP to the MoFe protein. AB - The dye-oxidized or dithionite-reduced forms of the MoFe protein of molybdenum nitrogenase of Azotobacter chroococcum were shown to bind 2 mol of MgADP/mol of protein, as determined by column equilibrium techniques. The gel-filtration elution profile of unbound Mg[14C]ADP was not symmetrical, consistent with a low rate of dissociation from the protein. Symmetrical elution profiles were observed for the oxidized Fe protein of nitrogenase, which bound 2 mol of MgADP/mol of protein. The low rate of dissociation of MgADP from MoFe protein was shown by non equilibrium column techniques, where 1 mol of MgADP/mol of MoFe protein remained tightly bound during chromatography. Very weak binding of MgATP (less than 0.01 mol of MgATP/mol of MoFe protein) to dye-oxidized but not to dithionite-reduced MoFe protein was observed. These results are discussed in terms of their relevance to the catalytic cycle of nitrogenase catalysis. PMID- 2597126 TI - Effects of inducers of drug metabolism on basic hepatic forms of mouse glutathione transferase. AB - The cytosolic glutathione transferases (GSTs) with basic pI values have been studied in mouse liver after treatment with 2,3-t-butylhydroxyanisole (BHA), cafestol palmitate (CAF), phenobarbital (PB), 3-methylcholanthrene (3-MC) and trans-stilbene oxide (t-SBO). The cytosolic GST activity was induced by all compounds except for 3-MC. Three forms of GST were isolated by means of affinity chromatography and f.p.l.c. The examination of protein profiles and enzymic activities with specific substrates showed that the three GSTs correspond to those found in control animals, i.e. GSTs MI, MII and MIII. The class Mu GST MIII accounted for the major effect of induction, whereas the class Alpha GST MI and the class Pi GST MII were unchanged or somewhat down-regulated. The greatest induction was obtained with BHA, PB and CAF. The activities of other glutathione dependent enzymes were also studied. An increase in glutathione reductase and thioltransferase activities was observed after BHA, PB or CAF treatment; glyoxalase I and Se-dependent glutathione peroxidase were depressed in comparison with the control group in all cases studied. PMID- 2597128 TI - Synthesis of hyaluronate in cultured bovine articular cartilage. AB - The synthesis and distribution of hyaluronate and proteoglycan were studied in bovine articular cartilage in short-term explant culture with [3H]acetate and H2(35)SO4 as precursors. The incorporation of [3H]acetate into hyaluronate and sulphated glycosaminoglycans was linear with time, except that hyaluronate synthesis showed a marked lag at the beginning of the incubation. [3H]Hyaluronate represented 4-7% of the total [3H]glycosaminoglycans synthesized over a 6 h period. However, the distributions of [3H]hyaluronate and 3H-labelled sulphated glycosaminoglycans were different: about 50% of the newly synthesized [3H]hyaluronate appeared in the medium, compared with less than 5% of the 3H labelled sulphated proteoglycans. A pulse-chase experiment revealed that the release of newly synthesized [3H]hyaluronate from cartilage was rapid. No difference was observed in the distribution of [3H]hyaluronate between medium and tissue by cartilage from either the superficial layer or the deep layer of articular cartilage. When articular cartilage was incubated with 0.4 mM cycloheximide, proteoglycan synthesis was markedly inhibited, whereas the synthesis of hyaluronate was only partially inhibited and resulted in more of the newly synthesized hyaluronate being released into the medium. Analysis of the hydrodynamic size of [3H]hyaluronate isolated from cartilage on Sephacryl-1000 revealed one population that was eluted as a broad peak (Kav. less than 0.7), compared with two populations (Kav. greater than 0.5 and less than 0.5) appearing in the medium of cultures. These data suggest that hyaluronate is synthesized in excess of proteoglycan synthesis and that the hyaluronate that is not complexed with proteoglycans is rapidly lost from the tissue. PMID- 2597129 TI - Electroneutral, HCO3(-)-independent, pH gradient-dependent uphill transport of Cl by ileal brush-border membrane vesicles. Possible role in the pathogenesis of chloridorrhea. AB - By applying a rapid filtration technique to isolated brush border membrane vesicles from guinea pig ileum, 36Cl uptake was quantified in the presence and absence of electrical, pH and alkali-metal ion gradients. A mixture of 20 mM Hepes and 40 mM-citric acid, adjusted to the desired pH with Tris base, was found to be the most suitable buffer. Malate and Mes could be used to replace the citrate, but succinate, acetate and maleate proved to be unsuitable. In the absence of a pH gradient (pHout:pHin = 7.5:7.5), Cl- uptake increased slightly when an inside-positive membrane potential was applied, but uphill transport was never observed. A pH gradient (pHout:pHin = 5.0:7.5) induced both a 400% increase in the initial Cl- influx rate and a long-lasting (20 to 300 s) overshoot, indicating that a proton gradient can furnish the driving force for uphill Cl- transport. Under pH gradient conditions, initial Cl- entry rates had the following characteristics. (1) They were unaffected by cis-Na+ and/or -K+, indicating the absence of Cl-/K+, Cl-/Na+ or Cl-/K+/Na+ symport activity. (2) Inhibition by 20-100 mM-trans-Na+ and/or -K+ occurred, independent of the existence of an ion gradient. (3) Cl- entry was practically unaffected by short circuiting the membrane potential with equilibrated potassium and valinomycin. (4) Carbonyl cyanide m-chlorophenylhydrazone was strongly inhibitory and so, to a lesser extent, was 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid [(SITS)], independent of the sign and size of the membrane potential. (5) Cl- entry was negligibly increased (less than 30%) by either trans-Cl- or -HCO3-, indicating the absence of an obligatory Cl-/anion antiport activity. In contrast, the height of the overshoot at 60 s was increased by trans-Cl-, indicating time dependent inhibition of 36Cl efflux. That competitive inhibition of 36Cl fluxes by anions is involved here is supported by initial influx rate experiments demonstrating: (1) the saturability of Cl- influx, which was found to exhibit Michaelis-Menten kinetics; and (2) competitive inhibition of influx by cis-Cl- and -Br-. Quantitatively, the conclusion is warranted that over 85% of the total initial Cl- uptake energized by a pH gradient involves an electroneutral Cl-/H+ symporter or its physicochemical equivalent, a Cl-/OH- antiporter, exhibiting little Cl- uniport and either Cl-/Cl- or Cl-/HCO3- antiport activities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2597130 TI - Conformational differences between two wheat (Triticum aestivum) 'high-molecular weight' glutenin subunits are due to a short region containing six amino acid differences. AB - 'High-molecular-weight' (HMW, high-Mr) glutenin subunits are protein constituents of wheat (Triticum aestivum) seeds and are responsible in part for the viscoelasticity of the dough used to make bread. Two subunits, numbered 10 and 12, are the products of allelic genes. Their amino acid sequences have been derived from the nucleic acid sequences of the respective genes. Subunit 10 has fewer amino acids than subunit 12, but migrates more slowly on SDS/PAGE (polyacrylamide-gel electrophoresis). This anomaly is due to between one and six of the amino acid differences between the subunits, localized towards the C terminal end of the proteins. This has been established by making chimaeric genes between the genes for subunits 10 and 12, transcribing and translating them in vitro and analysing the products by SDS/PAGE. The postulated conformational differences between subunits 10 and 12 are discussed in relation to current hypotheses for the structure of HMW glutenin subunits. PMID- 2597131 TI - Kinetic analysis of protein modification reactions at equilibrium. AB - A kinetic analysis is presented of reactions of protein modification, and/or of modification-induced enzyme inactivation, which can formally be described by a single exponential function, or by a summation of two exponential functions, of reaction time plus a constant term. The reaction schemes compatible with the kinetic formalism of these cases are given, and a simple kinetic criterion is described whereby the identification of one of these cases, strong negative protein modification co-operativity, may be carried out. The treatment outlined in this paper is applied to a case from the literature, the inactivation of glyceraldehyde-3-phosphate dehydrogenase by butane-2,3-dione [Asriyants, Benkevich & Nagradova (1983) Biokhimiya (Engl. Transl.) 48, 164-171]. PMID- 2597132 TI - Pathway of alpha-linolenic acid through the mitochondrial outer membrane in the rat liver and influence on the rate of oxidation. Comparison with linoleic and oleic acids. AB - The movement of alpha-linolenic acid (C18:3, n-3) through the mitochondrial outer membrane to oxidation sites was studied in rat liver and compared with the movement of linoleic acid (C18:2, n-6) and oleic acid (C18:1, n-9). All differ in the degree of unsaturation, but have the same chain length and the same position of the first double bond when counted from the carboxyl end. The following results were obtained. (1) The overall beta-oxidation in total mitochondria was in the order C18:3, n-3 greater than C18:2, n-6 greater than C18:1, n-9, independent of the amount of albumin in the medium. (2) The rate of formation of acylcarnitine from acyl-CoA was higher with oleoyl-CoA than with linoleoyl-CoA, and remained very low with alpha-linolenoyl-CoA for all concentrations studied. (3) When the formation of acylcarnitines originated from fatty acids (as potassium salts) in a medium containing CoA and ATP, the conversion of alpha linolenate was greater than that of linoleate, which in turn was greater than that of oleate. (4) Use of a more purified mitochondrial fraction, practically devoid of peroxisomes, did not modify the results obtained with alpha-linolenate. (5) alpha-Linolenoyl-CoA did not inhibit oxidation of labelled alpha-linolenate, whereas the other acyl-CoAs did. (6) Transfer to carnitine of all three fatty acids (as potassium salts) by carnitine palmitoyltransferase-I (CPT-I) was similarly inhibited by increasing concentrations of malonyl-CoA. (7) On using a fraction containing mitochondrial outer membranes, the formation of acylcarnitines from potassium salts of fatty acids was qualitatively and quantitatively similar to that found with whole mitochondria. (8) Our observations show that alpha-linolenoyl-CoA synthesized other than in the mitochondria cannot be used to any great extent by the mitochondria due to its configuration. However when added as the unactivated form, alpha-linolenate appears to be very quickly oxidized, but should first be activated by acyl-CoA synthetase in the mitochondrion itself. Then it is rapidly channelled to CPT-I. These enzymic sites are probably close together in the mitochondrial outer membrane. The different behaviour of the alpha-linolenic group compared with the other acyl groups in the studied pathway can be explained by a different spatial arrangement due to the number and position of the double bonds. PMID- 2597133 TI - Purification and characterization of benzaldehyde dehydrogenase I from Acinetobacter calcoaceticus. AB - Benzaldehyde dehydrogenase I was purified from Acinetobacter calcoaceticus by DEAE-Sephacel, phenyl-Sepharose and f.p.l.c. gel-filtration chromatography. The enzyme was homogeneous and completely free from the isofunctional enzyme benzaldehyde dehydrogenase II, as judged by denaturing and non-denaturing polyacrylamide-gel electrophoresis. The subunit Mr value was 56,000 (determined by SDS/polyacrylamide-gel electrophoresis). Estimations of the native Mr value by gel-filtration chromatography gave values of 141,000 with a f.p.l.c. Superose 6 column, but 219,000 with Sephacryl S300. Chemical cross-linking of the enzyme subunits indicated that the enzyme is tetrameric. Benzaldehyde dehydrogenase I was activated more than 100-fold by K+, Rb+ and NH4+, and the apparent Km for K+ was 11.2 mM. The pH optimum in the presence of K+ was 9.5 and the pI of the enzyme was 5.55. The apparent Km values for benzaldehyde and NAD+ were 0.69 microM and 96 microM respectively, and the maximum velocity was approx. 110 mumol/min per mg of protein. Various substituted benzaldehydes were oxidized at significant rates, and NADP+ was also used as cofactor, although much less effectively than NAD+. Benzaldehyde dehydrogenase I had an NAD+-activated esterase activity with 4-nitrophenol acetate as substrate, and the dehydrogenase activity was inhibited by a range of thiol-blocking reagents. The absorption spectrum indicated that there was no bound cofactor or prosthetic group. Some of the properties of the enzyme are compared with those of other aldehyde dehydrogenases, specifically the very similar isofunctional enzyme benzaldehyde dehydrogenase II from the same organism. PMID- 2597134 TI - Muscarinic cholinergic receptor of rat cerebral cortex. Location and characterization of ligand binding site-carrying peptides in synaptosomal membranes and isolated neuronal perikarya. AB - A careful examination of the location and biochemical properties of the tryptic peptides identified by site-specific labelling of the muscarinic cholinergic receptor (mAChR) of rat cerebral cortex has been carried out. In brain synaptosomal membranes and isolated neuronal perikarya, mAChR labelled with [3H]propylbenzilylcholine mustard (PrBCM) was tryptically cleaved to peptides of Mr 50,000, 30,000. 18,000 and a limiting fragment of Mr 8000. All of these binding site-carrying fragments, characterized in terms of their content of carbohydrates and thiol groups, were quantitatively recovered as membrane-bound peptides. The delipidated [3H]PrBCM-labelled tryptic limiting fragment was found to be highly hydrophobic and insoluble in aqueous media. Experiments performed with proteinase on the tryptic limiting fragment suggest the existence of an ester linkage between the ligand and the peptide. The results strongly support the hydropathicity profile which predicts the location of the muscarinic receptor protein with respect to the membrane bilayer. PMID- 2597135 TI - The use of benzyloxycarbonyl[125I]iodotyrosylalanyldiazomethane as a probe for active cysteine proteinases in human tissues. AB - The ability of benzyloxycarbonyl-(125I)Tyr-Ala-CHN2 to label cysteine proteinases in a variety of human tissues was investigated. The inhibitor bound only to cathepsin B in tissues homogenized at pH 5.0. When liver was autolysed at pH 4.0 for up to 4 h, the inhibitor also bound to a protein of Mr 25,000. This was identified immunologically and chromatographically as cathepsin L. Both cathepsins B and L were found primarily in kidney, liver and spleen. In spleen, an additional protein of Mr 25,000 was also labelled. This protein could not be precipitated by antibodies to any of cathepsins B, H and L. This protein has tentatively been identified as human cathepsin S by its tissue distribution, chromatographic properties and molecular size. This work clearly shows that peptidyldiazomethanes are specific probes for cysteine proteinases, and that benzyloxycarbonyl-(125I)Tyr-Ala-CHN2 binds to three such enzymes in human tissues. PMID- 2597136 TI - Calcium-binding protein from mouse Ehrlich ascites-tumour cells is homologous to human calcyclin. AB - A Ca2+-binding protein was purified from mouse Ehrlich ascites-tumour cells. The protein forms monomers and disulphide-linked dimers, which can be separated by reverse-phase h.p.l.c. A partial amino acid sequence analysis demonstrated that the protein has an EF-hand structure. A striking homology was found to rat and human calcyclin (a member of the S-100 protein family), which is possibly involved in cell-cycle regulation. PMID- 2597137 TI - Enantiomeric selectivity of adenosine transport systems in mouse erythrocytes and L1210 cells. AB - In mediating the entry of adenosine into mouse erythrocytes and mouse leukaemia L1210 cells, nucleoside transport systems were stereoselective, showing a marked preference for the D-enantiomer of adenosine (D-Ado). Inward zero-trans fluxes of the mirror-image isomer, L-adenosine (L-Ado), in those cells were slow relative to those of D-Ado. Contributing to L-Ado fluxes in both cell types were (i) a transporter-mediated process of high nitrobenzylthioinosine-sensitivity and (ii) simple diffusion. PMID- 2597138 TI - Variations in the rate of secretion of different glycosylated forms of rat alpha 1-acid glycoprotein. AB - Various studies have shown that oligosaccharides play an important role in the intracellular transport and secretion of glycoproteins. We show here a difference in the rate of secretion of two mature glycoforms of a single protein, alpha 1 acid glycoprotein. This indicates the existence of kinetically different pathways for these two forms for transport from the medial Golgi to the extracellular medium. PMID- 2597140 TI - The amino acid sequence of a flavodoxin from the eukaryotic red alga Chondrus crispus. AB - The amino acid sequence of the constitutive flavodoxin from the red alga Chondrus crispus was determined from the analyses of peptide fragments derived by enzymic digestions of the carboxymethylated protein. This is the first sequence reported for a flavodoxin from a eukaryote. The protein is composed of 173 amino acid residues and is a member of the longer-chain group of flavodoxins. The extent of sequence homology to the three other flavodoxins in the group for which sequences are available is in the range 36-39%, with the most strongly conserved regions being those implicated in binding of the FMN, the redox-active prosthetic group. Nevertheless, Chondrus crispus flavodoxin stands apart in a number of respects, in particular the possession of an unusually high content of proline, with these residues distributed more or less regularly along the peptide chain. PMID- 2597141 TI - Two types of rate-determining step in chemical and biochemical processes. AB - Close examination of the concept of the rate-determining step (RDS) shows that there are two types of RDS depending on the definition of 'rate'. One is represented by the highest peak of the free-energy diagram of consecutive reactions and holds true where the rate is defined in terms of the concentration of the first reactant. The other is represented by the peak showing the maximum free-energy difference, where the free-energy difference is the height of a peak measured from the bottom of any preceding troughs, where the definition of the rate is in terms of the total reactant concentration including intermediates. There are no criteria a priori for selecting one of them. PMID- 2597139 TI - Receptor- and phorbol-ester-mediated redistribution of protein kinase C in human platelets. Evidence that aggregation promotes degradation of protein kinase C. AB - Translocation of Ca2+/phospholipid-dependent protein kinase (PKC) activity from cytosolic to membrane fractions was assessed in washed human platelet suspensions. Phorbol myristate acetate (PMA) induced a rapid loss of PKC activity from the cytosolic compartment in stirred platelets, which was not accompanied by measurable increases in membrane-associated activity, but was paralleled by a decrease in total cellular enzyme activity (cytosol plus membrane). When platelet aggregation was prevented by not stirring, (i) cytosolic activity was decreased by PMA, (ii) significant and maintained (1-15 min with PMA) increases in membrane bound PKC were detected, and (iii) the decline in total enzyme activity was markedly slower. In stirred platelets, total and specific inhibition of PMA induced aggregation by a fibrinogen-derived peptide (RGDS, i.e. Arg-Gly-Asp-Ser) promoted maximal increases in membrane-associated PKC in the presence of PMA and completely prevented the loss in cellular activity. Thrombin and collagen both induced a decrease in cytosolic PKC and a loss of total activity, but a significant rise in membrane activity was seen only with collagen; ADP had no detectable effect on enzyme distribution. These results demonstrate an agonist induced redistribution of PKC and indicate that platelet aggregation may play an important role in the proteolysis, and hence persistence, of membrane-associated PKC. This observation has implications for the potency and duration of PKC mediated responses induced by agonists and exogenous PKC activators. PMID- 2597142 TI - Studies on human red-cell membrane glycophorin A and glycophorin B genes in glycophorin-deficient individuals. AB - 1. Genomic DNA derived from individuals who lack glycophorin A (GPA), glycophorin B (GPB) or both of these proteins was subjected to Southern-blot analysis using GPA and GPB cDNA probes. 2. Bands on the Southern blots were assigned to the GPA gene, GPB gene or to a putative pseudogene. 3. Genomic DNA derived from an individual of the Mk phenotype was shown to have deletions in the GPA and GPB genes. The simplest model for the results obtained is that a single deletion spans the GPA and GPB genes in the individual studied. PMID- 2597143 TI - An n.m.r. study of the tricarboxylic acid cycle. PMID- 2597144 TI - The fate of [3-13C]citrate in renal cells monitored by 13C n.m.r. PMID- 2597145 TI - Studies of MR 889, a new synthetic proteinase inhibitor. AB - We investigated the proteinase inhibitory activity of MR 889, a thiolactic acid derivative. It is able to in vitro inhibit at low concentration (10(-5),10(-6)M) the activity of porcine pancreatic elastase, human neutrophil elastase and bovine chymotrypsin. In addition, MR 889 is able to inhibit the residual activity of alpha 2-macroglobulin-trapped human neutrophil elastase, paralleling the efficacy of phenylmethylsufonylfluoride. Finally, MR 889 has been shown to in vitro reduce the burden of elastase- and chymotrypsin-like activity found in sputum sol-phases of patients admitted for chronic bronchitis exacerbation. PMID- 2597146 TI - Superinduction of the human gene encoding low density lipoprotein receptor. AB - Expression of human LDL receptor mRNA and protein is induced in human glioblastoma-astrocytoma cells upon transfer into lipoprotein-deficient medium, a mode of induction likely to be physiological. The presence of cycloheximide (CHX) leads to up to 7.5-fold superinduction of LDL receptor mRNA within 4 hr and, upon removal of this inhibitor, to superinduction of LDL receptor protein as well. The extent of superinduction of LDL receptor mRNA reaches over 40-fold beyond the level expressed in medium containing regular serum. Despite its extensive superinduction, LDL receptor mRNA decays rapidly in the presence of CHX. Stabilization of LDL receptor mRNA is thus unlikely to account for the observed superinduction. These results show that normally the LDL receptor gene is expressed to only a small fraction of its full potential. PMID- 2597147 TI - Messenger RNA for manganese and copper-zinc superoxide dismutases in hepatomas: correlation with degree of differentiation. AB - Total and polyadenylylated RNA have been isolated from two Morris hepatomas with different degree of differentiation and from the normal liver of the corresponding tumor-bearing inbred rats. The analysis of mRNA has been performed by Northern hybridization using 32P-dA-tailed synthetic deoxyoligonucleotide probes, 33-mer for Mn superoxide dismutase (SOD) and 36-mer for CuZnSOD, derived from the nucleotide sequences of the rat enzyme cDNAs. Two distinct mRNA species (about 850 and 1080 nucleotides) have been identified by using the MnSOD probe. CuZnSOD is translated from a single message of about 720 nucleotides. The total MnSOD mRNA concentration is decreased by 43% and 57% in the hepatomas 9618A (highly differentiated) and 3924A (poorly differentiated), respectively. CuZnSOD mRNA is practically unchanged in the hepatoma 9618A whereas it is reduced by 80% in the hepatoma 3924A. Comparison of the enzyme activities and mRNA levels indicates a good correlation only for hepatoma 3924A, suggesting that the changes of both SODs are regulated pretranslationally. From the data obtained it is also inferred that the mRNA levels of MnSOD respond more readily than those of CuZnSOD to changes in differentiation. PMID- 2597148 TI - Purification of bone morphogenetic protein derived from bovine bone matrix. AB - Bone morphogenetic protein (BMP) was extracted from the bovine bone matrix and purified by liquid chromatography. The molecular weight of the BMP was 18 kDa by SDS-PAGE, and its pI value was 4.9. Amino acid analysis suggested that the BMP is a polypeptide containing 163 amino acids. In the present study, telopeptide-free type I collagen was used as a carrier of BMP. PMID- 2597149 TI - Conformational variations in d(TGACGTCA) and its reverse sequence d(ACTGCAGT): a joint circular dichroism and nuclear magnetic resonance study. AB - Circular dichroism (CD) and nuclear magnetic resonance (NMR) techniques have been used to characterize the structural properties of the two self-complementary DNA octamers d(TGACGTCA) (I) and d(ACTGCAGT) (II). These display as distinctive features reverse sequences and central steps CpG and GpC, respectively. CD experiments lead to B-form DNA spectra characterized by larger magnitude signals in the case of octamer (I). NMR COSY spectra indicate that in the two octamers all the residues are predominantly south, S, (2'-endo) sugar conformation. NMR NOESY spectra show most of the glycosidic angles confined in the range predicted for B-form DNA although important heterogeneity is noticed along the chains, more pronounced in the case of octamer (I). Both the increase of north, N, (3'-endo) sugar conformation and P (pseudorotation phase angle) deviation from its standard B-form DNA value (162 degrees) express local sequence dependent structure distortions, remarkably visible in CpG step of octamer (I) and agreeing with NOESY cross-peaks intensities. Results interpreted according to Calladine's rules indicate higher cross-chain strains in octamer (I) than in octamer (II). All together, we find evidence to support for octamer (I) in solution local structures with A-DNA properties likely dictated by the central CpG step. Such structures could be involved in the DNA recognition by proteins and anticancerous drugs. PMID- 2597150 TI - Structural changes in cellobiohydrolase I upon binding of a macromolecular ligand as evident by SAXS investigations. AB - Xylan from Rhodymenia palmata binds to the cellobiohydrolase I from Trichoderma reesei (CBH I) or its core protein, inhibiting their activity. Adsorption onto microcrystalline cellulose (Avicel) is reduced approximately 30% for intact CBH I and nearly 50% for the core, whereas the effects with cellobiose are negligible. Structural changes concomitant with this binding are studied in solution by small angle X-ray scattering. In the "tadpole" structure typical for the CBH I [Abuja et al., 1988] the lengthening of the tail part is the most salient observation when xylan is present which accounts for an increase in Dmax (18.0 to 22.0 nm) and radius of gyration (4.74 to 5.18 nm). When xylan binds to the core the radius of gyration remains nearly unchanged. Here a model can be constructed showing a xylan molecule on the surface of the core protein near the tail part. PMID- 2597152 TI - Human and canine gene homologs of porcine brain natriuretic peptide. AB - A cDNA clone encoding porcine brain natriuretic peptide (BNP) precursor was used to probe a canine genomic DNA library for homologous sequences. A unique clone was obtained (D1) which encoded a peptide homologous to porcine BNP. A 4.0 kB Hind III fragment of D1 containing the entire BNP precursor coding region was hybridized against blots of EcoRI digested human genomic DNA. A 7.0 kB hybridizing band was observed, which was subsequently subcloned and sequenced. This human clone, H1, also contained a sequence homologous to porcine BNP precursor. Transcription of the human BNP gene was confirmed by detection of BNP specific sequences amplified from human atrial RNA by polymerase chain reaction. These results suggest that both BNP and ANP are present and function in a wide variety of mammalian species. PMID- 2597151 TI - Sequence analysis of the 5' region of the human DF3 breast carcinoma-associated antigen gene. AB - DF3 antigen is a high molecular weight glycoprotein detectable in human breast carcinomas. Recent studies have demonstrated that the gene coding for the DF3 core protein consists in part of highly conserved 60 base pair tandem repeats. The present work extends these findings by identifying the region of the DF3 gene 5' to the repeats. The results of primer extension studies demonstrate that the transcription start site of the cDNA is 384 base pairs upstream to the first tandem repeat. Comparison of the cDNA and genomic sequences has demonstrated that the sequences transcribed upstream to the repeats are interrupted by the presence of an intron at 124 bases after the start site. We have also identified the putative promoter region of the DF3 region. This region has several elements, including a TATA sequence and multiple GC boxes, that may be involved in the regulation of DF3 gene transcription. PMID- 2597153 TI - Fast-growing root nodule bacteria produce a novel polyamine, aminobutylhomospermidine. AB - Polyamines in various root nodule bacteria including Bradyrhizobium japonicum, Rhizobium fredii, R. leguminosarum, R. meliloti and R. loti were identified by capillary gas chromatography. Homospermidine was the polyamine present in highest concentration in all the rhizobia tested. In addition to putrescine and homospermidine, fast-growing type of rhizobial cells contained a novel polyamine, aminobutylhomospermidine, NH2(CH2)4NH(CH2)4NH(CH2)4NH2. The unusual tetraamine was not found in the cells of slow-growing type of rhizobia throughout their growth period, indicating a difference in polyamine metabolism between fast growing type and slow-growing type of root nodule bacteria. PMID- 2597154 TI - NADH- and NADPH-linked aquacobalamin reductases occur in both mitochondrial and microsomal membranes of rat liver. AB - To elucidate the mechanism for the synthesis of the coenzyme forms of cobalamin in mammals, rat liver aquacobalamin reductase was partially characterized. Rat liver contained both NADH- and NADPH-linked aquacobalamin reductases. The NADH linked enzyme was distributed in the mitochondria (approx. 40%) and microsomes (60%), identical to the distribution of the NADPH-linked enzyme. The two mitochondrial NADH- and NADPH-linked enzymes were located inside of the outer membrane. PMID- 2597155 TI - Phospholipids differently modulate the activity of cytosolic protein-tyrosine kinase from porcine spleen. AB - Effect of membrane phospholipids on the activity of cytosolic protein-tyrosine kinase from porcine spleen (CPTK-40) has been studied. Using poly(Glu Na, Tyr)4:1 as a substrate, phosphatidylethanolamine, phosphatidylcholine and phosphatidylserine had stimulatory effects on that phosphorylation activity, however phosphatidic acid had inhibitory and phosphatidylinositol had no effects. Similar results were obtained using[Val5]angiotensin II as a substrate. On the other hand using basic protein (H2B histone and myelin basic protein) as substrates, phosphatidic acid stimulated the activity of CPTK-40, while phosphatidylinositol inhibited the activity. Phosphatidylethanolamine, phosphatidylcholine and phosphatidylserine caused different effect on the activity of CPTK-40 depending on the substrate employed. However using acidic protein (tubulin and casein) as substrates, the activity of CPTK-40 was neither stimulated nor inhibited by any phospholipids. These results suggest that phospholipids may modulate the activity of CPTK-40. PMID- 2597156 TI - Taipoxin-binding protein on synaptic membranes: identification by affinity labeling. AB - Affinity labeling techniques were used to identify the neuronal membrane molecules involved in the binding of taipoxin, a neurotoxic protein with phospholipase A2 activity. After [125I]taipoxin had bound to synaptosomes from guinea pig brain, treatment with disuccinimidyl suberate resulted in the formation of a predominant radioactive conjugate of 60,000 Da. Notexin and some other PLA2s are weakly inhibitory to this conjugation, while beta-bungarotoxin and some others are not inhibitory. The 60K conjugate was not detected when plasma membranes from several nonneuronal tissues were used. We concluded that a 45,000 Da protein specifically present in neuronal membranes is (a subunit of) the major molecule responsible for taipoxin binding. PMID- 2597157 TI - Corticotropin-releasing factor-binding protein is a glycoprotein. AB - Human corticotropin-releasing factor-binding protein (hCRF-BP), a 38,000 dalton protein, specifically binds hCRF in plasma. CRF-BP-CRF complex adsorbed to concanavalin-A-Sepharose and its Mr decreased after treatment with endoglycosidase H or glycopeptidase A. The binding of CRF-BP to CRF decreased after treatment with endoglycosidase H. These results indicate that the CRF-BP is a glycoprotein that contains asparagine N-linked-type oligosaccharides, and such oligosaccharide chains are important for CRF-BP binding. PMID- 2597158 TI - Molecular cloning of new human TR2 receptors: a class of steroid receptor with multiple ligand-binding domains. AB - Previously we isolated a new group of cDNA clones from human testis cDNA libraries which might code for new steroid receptors. The cDNA and predicted amino acid sequences of two of these receptors, named TR2-5 and TR2-7 receptors, were determined. We report here the nucleotide and deduced amino acid structures of two other receptors that we named TR2-9 and TR2-11 receptors. The calculated MW of TR2-5 receptor, TR2-7 receptor, TR2-9 receptor and TR2-11 receptor are 52,982, 20,528, 50,849 and 67,223 respectively, which match well with the apparent MW of in vitro translated products. The 26 amino acids involved in the formation of "Zn-fingers" are conserved. The ligand-binding domain of TR2-9 receptor is 16 amino acids shorter and has 3 different amino acids compared with TR2-5 receptor. The TR2-11 receptor has a ligand-binding domain which is longer and quite different compared with the other TR2 receptors. The multiple ligand binding domains of TR2 receptor could be the products of different genes or may be due to RNA splicing errors. So far, we have failed to find binding activity with any known steroid hormone; this promotes the possibility that an unidentified steroid hormone may be involved. PMID- 2597159 TI - Static quenching of tryptophan fluorescence by oxidized dithiothreitol. AB - The quenching of fluorescence of 5-methoxyindole, N-acetyl-L-tryptophanamide and two single tryptophan containing peptides, melittin and mastoparan X, by oxidized dithiothreitol was studied. The slopes of the Stern-Volmer plots for steady-state fluorescence quenching were 133 M-1, 71.2 M-1, 75.5 M-1 and 35.0 M-1 at 21 degrees C and pH 7.0 for 5-methyoxyindole, N-acetyl-L-tryptophanamide, melittin and mastoparan X respectively. Fluorescence lifetimes of indole or tryptophan in these compounds, as determined by multifrequency phase fluorometry, were decreased by 15% or less at concentrations that produced 50% or more quenching of steady-state fluorescence. Thus, quenching of fluorescence by oxidized dithiothreitol for these derivatives of indole appears to be largely static in nature, suggesting a ground-state interaction. PMID- 2597160 TI - Expression of the ED B fibronectin isoform in adult human articular cartilage. AB - The most recently described region of alternate splicing of fibronectin mRNA results in expression of an isoform which includes the type III repeat termed ED B (EIII B). To date this isoform has been detected in transformed cells in culture, in the synovial membrane and ovary but in no other adult tissue, and in embryonic chick cartilage to a much greater extent than in other cells of mesenchymal origin. Monoclonal antibody BC-1, which recognizes an epitope within the ED B segment, was used in two different assays and provided evidence that adult human articular cartilage contains ED B fibronectin. The extent of expression of this isoform, however, was variable and less than that found in fibronectin produced by the transformed fibroblast cell line WI-38VA13. PMID- 2597161 TI - Immunological studies on the participation of 6-pyruvoyl tetrahydropterin (2' oxo) reductase, an aldose reductase, in tetrahydrobiopterin biosynthesis. AB - The NADPH-dependent reduction of the two carbonyl groups in the side chain of the first tetrahydropterin intermediate on the tetrahydrobiopterin biosynthetic pathway, 6-pyruvoyl tetrahydropterin, proceeds in a sequential manner whose order has not yet been resolved. Sepiapterin reductase can catalyze the reduction of both carbonyl groups starting with the 1'-oxo. 6-Pyruvoyl tetrahydropterin (2' oxo) reductase, which has now been shown to be a member of the aldose reductase family, catalyzes the formation of only the 2'-hydroxy-1'-oxo intermediate which still requires sepiapterin reductase for final conversion to tetrahydrobiopterin. Inhibiting antibodies to the 2'-oxo reductase have been prepared and utilized to explore the distribution of this reductase in rat brain. The antiserum also maximally inhibited in vitro tetrahydrobiopterin synthesis in crude rat brain extracts by 60%, indicating that the majority of tetrahydrobiopterin biosynthesis in vivo may proceed via the 2'-hydroxy-1'-oxo intermediate. However, analogous experiments with rat liver extracts demonstrate that inhibition of the 2'-oxo reductase activity does not inhibit the conversion of 6-pyruvoyl tetrahydropterin to tetrahydrobiopterin, suggesting that tetrahydrobiopterin biosynthesis may proceed via different pathways in rat brain and liver. PMID- 2597162 TI - Apolipoprotein E*3-Leiden allele results from a partial gene duplication in exon 4. AB - The apolipoprotein E3-Leiden variant has been shown to be associated with familial dysbetalipoproteinemia (FD) in a dominant manner (Havekes et al., Hum Genet 1986;73:157-163). Applying the polymerase chain reaction technique, we have cloned and sequenced relevant parts of both APOE alleles of the original proband. In exon 4 of the E*3-Leiden allele a partial gene duplication encompassing 21 nucleotides was found, leading to a tandem repeat of the codons 120-126 or 121 127. Using an E3-Leiden mutation specific oligonucleotide probe, the same mutation was found in two additional independently ascertained FD patients with an E3E3 phenotype based on isoelectric focusing. The E*3-Leiden mutation will be useful in the elucidation of the etiology of dominantly inherited forms of FD. PMID- 2597163 TI - The rapidly phosphorylated chromosomal 42-kDa protein is a subunit of larger protein complexes. AB - We have isolated, purified and characterized a 42-kDa phosphoprotein which has been found to be preferentially associated with active gene loci of salivary gland cells of Chironomus tentans. The rapidly phosphorylated form of this protein could be extracted with 0.2 M NaCl. Chromatographic analysis by gel filtration revealed that a significant fraction of labelled 42-kDa polypeptide elutes with an apparent molecular mass of 150 to 200 kDa. The result suggests that a portion of the phosphorylated 42-kDa polypeptide in native state forms a multisubunit protein complex consisting of rapidly phosphorylated 42-kDa polypeptide chains alone. PMID- 2597164 TI - Complementary DNA for the mouse homolog of the small subunit of human cytochrome b558. AB - Cytochrome b558, a heterodimeric protein, is considered to be a component of the microbicidal oxidase in phagocytes. We have isolated a cDNA clone for the mouse homolog of the small subunit of human cytochrome b558. Comparison of the predicted amino acid sequence with that of the human protein reveals a high degree of homology (87%). As expected, the mRNA is expressed abundantly in peritoneal neutrophils and, to a lesser extent, in peritoneal macrophages. The transcript is also abundant in the mouse kidney. Although the spleen and small intestine contain considerable amounts of the mRNA, only trace amounts are detected in the brain, liver, testis and heart. The distribution, especially its high expression in the kidney, may suggest another function of the small subunit. PMID- 2597165 TI - Phospholipase C activity reduces free magnesium concentration. AB - The events leading to decline of intracellular free magnesium concentration following traumatic brain injury are unknown. One possible mechanism that may lead to such declines is an alteration in the number and nature of magnesium binding sites within cell membranes following a traumatic event. Although both alterations in membrane structure and decrease in free magnesium concentration have been independently demonstrated to occur following brain trauma, no correlations between the two events have been shown. In the present study, rat brain phospholipids were extracted and reconstituted in MgATP containing aqueous solutions. Using 31P magnetic resonance spectroscopy to measure free magnesium concentration, enzymatic hydrolysis of the artificial membrane vesicles by phospholipase C was shown to reduce the free magnesium concentration. Since activation of phospholipase C has been demonstrated to occur following traumatic brain injury, we propose that this event may initiate decline in free magnesium levels in vivo. PMID- 2597166 TI - Inhibition by polyamines of methylthiopropylamine-induced ornithine decarboxylase in human lymphoid leukemia Molt 4B cells. AB - Methylthiopropylamine (MTPA), an inhibitor of spermidine synthase, markedly induced ornithine decarboxylase (ODC) activity (about 30-fold of the basal level) in human lymphoid leukemia Molt 4B cells. This induction was blocked by the addition of spermidine, spermine or putrescine simultaneously with MTPA. Inhibition by spermidine or spermine of the MTPA-induced ODC activity was larger than that by putrescine. The increase of ODC activity by MTPA led to the large increase of cellular putrescine content. This increase of putrescine content was abolished drastically by the simultaneous addition of spermidine or spermine. The increase of ODC activity was almost completely blocked by the addition of cycloheximide or actinomycin D. This finding suggested that the increase of ODC activity was not due to activation of ODC preformed in Molt 4B cells. The ODC induction by MTPA was dose-dependently blocked by adding the calcium channel blockers (verapamil and nifedipine) or protein kinase C inhibitors (1-(5 isoquinolinesulfonyl)-2-methylpiperazine and palmitoyl carnithine). These results suggested that calcium and protein kinase C (PKC) were involved in MTPA associated induction of ODC. PMID- 2597167 TI - Transient depletion of nucleus accumbens dopamine content may contribute to initial akinesia induced by MPTP in common marmosets. AB - Acute treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) caused an initial profound akinesia and other motor deficits. However, over the following months akinesia gradually disappeared although the animals remained clumsy and poorly coordinated. At 10 days following MPTP treatment there was a profound decrease in the dopamine, HVA and DOPAC content of the caudate nucleus, putamen and nucleus accumbens. By 3-4 months following MPTP treatment the animals had largely recovered from their akinesia, but the caudate nucleus and putamen dopamine, HVA and DOPAC content remained low. In contrast, the dopamine content of the nucleus accumbens had returned towards normal and the metabolite levels were higher than at 10 days. No overall alterations in 5HT or 5HIAA levels were observed at either time point. The transient and reversible nature of dopamine loss in the nucleus accumbens may contribute to the initial profound akinesia exhibited by common marmosets treated with MPTP. The restoration of dopamine levels in the nucleus accumbens may be partially responsible for the subsequent recovery of motor function that occurs in MPTP-treated marmosets. PMID- 2597168 TI - Aristololactam-beta-D-glucoside. A new DNA binding monofunctional intercalating alkaloid. AB - The binding of aristololactam-beta-D-glucoside to DNA is characterized by hypochromism and bathochromism in the absorption band, quenching of the fluorescence intensity, increase in the positive and negative ellipticity of DNA, enhancement of thermal transition temperature, sign and magnitude of thermodynamic parameters, increase of the contour length of sonicated rod-like DNA and induction of the unwinding-rewinding process of covalently closed superhelical DNA. Binding parameters determined from absorbance and fluorescence titration by Scatchard analysis, according to an excluded-site model, indicate a very high affinity towards DNA. The binding of the alkaloid is an exothermic process with Gibbs free energy of -7.4 kcal/mol, van't Hoff enthalpy of -13.8 kcal/mol and entropy of -21.5 cal/degree/mol at 25 degrees. On the basis of these observations it is concluded that aristololactam-beta-D-glucoside binds to DNA by a mechanism of intercalation. PMID- 2597169 TI - Toxicity of the cysteine-S-conjugates and mercapturic acids of four structurally related difluoroethylenes in isolated proximal tubular cells from rat kidney. Uptake of the conjugates and activation to toxic metabolites. AB - Isolated proximal tubular cells from rat kidney were incubated with the cysteine S-conjugates and corresponding mercapturates of the potent nephrotoxicants tetrafluoroethylene (TFE), chlorotrifluoroethylene (CTFE), 1,1-dichloro-2,2 difluoroethylene (DCDFE) and 1,1-dibromo-2,2-difluoroethylene (DBDFE). Toxicity of these S-conjugates was determined by their ability to inhibit alpha methylglucose uptake by the cells. The cytotoxicity of the cysteine-S-conjugates and mercapturates of TFE and CTFE was similar, but the cysteine-S-conjugates of DCDFE and DBDFE were more toxic than their mercapturates. The cytotoxicity of the conjugates decreased in the following order TFE approximately CTFE greater than DCDFE greater than DBDFE, which is the same as observed in vivo. Inhibition of renal cysteine-S-conjugate beta-lyase by aminooxyacetic acid alleviated the cytotoxicity of both the cysteine-S-conjugates and the mercapturic acids of the four haloethylenes. The cytotoxicity of the mercapturates, but not of the cysteine-S-conjugates, could be reduced by probenecid, suggesting that the cysteine-S-conjugates are transported by a different carrier system than the mercapturates. The deacetylation of the mercapturates of TFE and CTFE in the cells was much higher than that of the mercapturates of DCDFE and DBDFE. The cysteine-S-conjugates of DCDFE and DBDFE were N-acetylated by the cells whereas the other cysteine-S-conjugates were not (TFE) or only marginally (CTFE) N acetylated. The observed differences in cytotoxicity may be explained by differences in (1) the balance between acetylation/deacetylation by the cells, (2) the conversion rate of the S-conjugates to toxic metabolites by renal beta lyase and (3) the transport into the proximal tubular cells. PMID- 2597170 TI - Tianeptine, a new tricyclic antidepressant metabolized by beta-oxidation of its heptanoic side chain, inhibits the mitochondrial oxidation of medium and short chain fatty acids in mice. AB - Tianeptine is a new tricyclic antidepressant which is metabolized mainly by beta oxidation of its heptanoic side chain. We determined the effects of tianeptine on the mitochondrial oxidation of natural fatty acids in mice. In vitro, tianeptine (0.5 mM) inhibited by only 32% the formation of beta-oxidation products from [1 14C]palmitic acid by hepatic mitochondria, but inhibited by 71% that from [1 14C]octanoic acid and by 51% that from [1-14C]butyric acid. The activity of the tricarboxylic acid cycle, assessed as the in vitro formation of [14C]CO2 from [1 14C]acetylcoenzyme A was decreased by 51% in the presence of tianeptine (0.5 mM). The inhibition of both beta-oxidation and the tricarboxylic acid cycle appeared reversible in mitochondria from mice exposed to tianeptine in vivo but incubated in vitro without tianeptine. In vivo, administration of tianeptine (0.0625 mmol/kg i.p.), decreased by 53 and 58%, respectively, the formation of [14C]CO2 from [1-14C]octanoic acid and [1-14C]butyric acid, but did not significantly decrease that from [1-14C]palmitic acid. After administration of high doses of tianeptine, however, formation of [14C]CO2 from [1-14C]palmitic acid became inhibited as well, transiently after 0.25 mmol/kg and durably (greater than 24 hr) after 0.75 mmol/kg i.p. Hepatic triglycerides were increased 24 hr after administration of 0.75 mmol/kg i.p. of tianeptine, but not after 0.25 mmol/kg i.p. Microvesicular steatosis of the liver was observed in some mice after 0.75 mmol/kg i.p., but not after 0.5 mmol/kg i.p. We conclude that tianeptine inhibits the oxidation of medium- and short-chain fatty acids in mice. Microvesicular steatosis, however, requires very large doses in mice (0.75 mmol/kg i.p., i.e. 600-times the oral dose in humans), and is therefore unlikely to occur in humans. PMID- 2597171 TI - Thienamycin nephrotoxicity. Mitochondrial injury and oxidative effects of imipenem in the rabbit kidney. AB - The nephrotoxic cephalosoprins cephaloridine and cephaloglycin both produce mitochondrial respiratory toxicity in renal cortex. Recent work has provided evidence that this respiratory toxicity is caused by acylation and inactivation of mitochondrial anionic substrate transporters. While cephaloridine also causes significant lipid peroxidative injury in cortical mitochondria and microsomes, cephaloglycin causes little or no oxidative damage under identical conditions. The recently released thienamycin antibiotic, imipenem, like the toxic cephalosporins, produces acute proximal tubular necrosis which can be prevented completely by prior administration of probenecid. The ability of imipenem to block mitochondrial substrate uptake and respiration and produce oxidative changes has not been examined. We therefore evaluated the effects of imipenem in rabbit renal cortex on the following: (1) mitochondrial function [respiration with and uptake of succinate, and uptake of ADP]; and (2) evidence of oxidative change [depletion of reduced glutathione (GSH), production of oxidized glutathione (GSSG), and production of lipid peroxidative injury, as reflected in microsomal conjugated dienes (CDs)]. The mitochondrial effects of 300 mg/kg body wt of imipenem, given i.v. 1 and 2 hr before killing the animals, were comparable to those of the nephrotoxic cephalosporins. There was significant reduction of respiration with, and unidirectional uptake of, succinate at both times, while mitochondrial ADP transport was comparatively unaffected. Imipenem also depleted GSH and increased GSSG and CDs at 1 hr. These effects, however, were considerably smaller than those of a comparably nephrotoxic dose of cephaloridine, and this evidence of oxidative stress had resolved by 2 hr. We conclude that imipenem and the nephrotoxic cephalosporins have similar effects on mitochondrial substrate uptake and respiration, but differ significantly in their production of oxidative injury. PMID- 2597172 TI - Inhibition of uridine phosphorylase from Giardia lamblia by pyrimidine analogs. AB - Fifty-six pyrimidine analogs were tested as possible inhibitors of uridine phosphorylase from Giardia lamblia. Values of Ki were determined for eight of these which demonstrated an inhibition greater than 60% under the standard conditions of uridine at 1 mM (approximately 1.5 times the Km) and inhibitor at 1 mM. All were competitive with respect to uridine. The most effective inhibitors were uracil analogs substituted at the C-5 position with electron withdrawing groups (nitro groups or halogens). The inhibitory effect at the 5-position appeared to be further enhanced by substitution at the C-6 position with electron releasing groups. The order of effectiveness as inhibitors was 6-methyl-5 nitrouracil greater than 6-amino-5-nitrouracil greater than 5-benzylacyclouridine greater than 5-nitrouracil greater than 5-fluorouracil greater than 5-bromouracil greater than 6-benzyl-2-thiouracil greater than 1,3-dimethyluracil with Ki values of 10, 12, 44, 56, 119, 230, 190 and greater than 1000 microM, respectively. The compounds were also effective inhibitors of the thymidine phosphorylase activity of the enzyme. The effect of the more potent compounds on G. lamblia in in vitro culture are currently under investigation. PMID- 2597173 TI - Protein thiol depletion and the killing of cultured hepatocytes by hydrogen peroxide. AB - The H2O2 generated by menadione kills cultured hepatocytes by a mechanism that depends in large part on a cellular source of ferric iron. Chelation of this iron by deferoxamine reduced by two-thirds the number of dead cells without any effect on the loss of 30% of total protein thiols, the formation of protein mixed disulfides, or the accumulation of oxidized glutathione (GSSG). The loss of protein thiols was accounted for by the formation of glutathione mixed disulfides from GSSG and the arylation of protein nucleophiles by menadione. Nevertheless, such a loss occurred despite the chelation of cellular iron and a substantial reduction in the extent of cell killing. With the H2O2 generated by glucose oxidase, lipid peroxidation and a loss of 40% of the total protein thiols accompanied the cell killing within 1 hr. Deferoxamine, superoxide dismutase and the antioxidant N,N'-diphenyl phenylenediamine (DPPD) prevented the cell killing and two-thirds of the loss of protein thiols. Peroxidation of liver microsomes in vitro with ADP:Fe3+ similarly depleted protein thiols, an effect that was prevented by DPPD. The supernatant fraction from the peroxidation assay depleted the protein thiols of cultured hepatocytes without an effect on viability. Thus, lipid peroxidation accounted for the major part of the loss of protein thiols with glucose oxidase. The 10-15% decrement in protein thiols after 1 hr that occurred in the absence of cell killing reflected the formation of glutathione mixed disulfides. Finally, in the presence of DPPD, glucose oxidase killed 75% of the cells between 1 and 3 hr without any further change in protein thiols. Thus, under the conditions studied, the depletion of protein thiols by the three mechanisms, namely lipid peroxidation, formation of glutathione mixed disulfides, and arylation, does not necessarily have a causal relationship to the killing of cultured hepatocytes. PMID- 2597174 TI - A selective binding site for 3H-NECA that is not an adenosine A2 receptor. AB - In homogenates of NG108-15 cells, adenosine analogues activate adenylate cyclase with the following order of potency: N-ethylcarboxamidoadenosine (NECA) greater than 2-chloroadenosine greater than N6-(L-phenylisopropyl)-adenosine (PIA) = cyclohexyladenosine = 2-phenylaminoadenosine. Adenosine receptor antagonists inhibit NECA-stimulated adenylate cyclase activity with the order of potency 3 isobutyl-1-methyl-xanthine (IBMX) greater than theophylline greater than caffeine. These data suggest that these ligands act at an adenosine A2 receptor. There is an apparently homogenous population of saturable 3H-NECA binding sites in homogenates of NG108-15 cells. These sites have an affinity for 3H-NECA of approximately 1 microM, and are present at a density of approximately 10 pmol/mg protein. Unlabelled NECA, 2-chloroadenosine, IBMX and theophylline displace 3H NECA binding, with an order of potency that suggests that the 3H-NECA binding site may represent an adenosine A2 receptor. However, PIA, cyclohexyladenosine and 2-phenylaminoadenosine produce no detectable displacement of 3H-NECA binding at concentrations that produce a maximal stimulation of adenylate cyclase activity. Pretreatment of NG108-15 cells with either NECA or PIA produces a homologous desensitization of subsequent responses to all the adenosine analogues, with no effect on subsequent responses to a prostacyclin receptor agonist or NaF. This suggests that all the adenosine analogues examined activate an adenosine A2 receptor. Therefore, the 3H-NECA site at which PIA is inactive cannot represent this receptor. PMID- 2597175 TI - Absence of an isotope effect in induction of cytochrome P-450 and xenobiotic metabolizing enzyme activities by stable isotope-labelled phenobarbital isotopomers. PMID- 2597176 TI - Further characterization of neurotensin binding in the rat brain: levocabastine displaceable neurotensin binding sites are not histamine-H1 receptors. PMID- 2597177 TI - Inhibition of rat liver and duodenum soluble catechol-O-methyltransferase by a tight-binding inhibitor OR-462. AB - The inhibition kinetics of rat liver and duodenum soluble catechol-O methyltransferase (COMT) with a disubstituted catechol OR-462 was studied. After preincubation of the enzyme and inhibitor in the presence of magnesium and S adenyosylmethionine, an inhibition about thirty times greater than that without preincubation was observed. Reversible tight-binding inhibition was demonstrated with Ki values of 0.7 nM and 1.0 nM for liver and duodenum enzyme, respectively. Km values of 53.4 microM and 56.9 microM for substrate 3,4-dihydroxybenzoic acid and 23.0 microM and 17.5 microM for S-adenosylmethionine were calculated for liver and duodenum enzyme, respectively. A catalytic number of 24/min for liver soluble COMT was calculated. PMID- 2597178 TI - Glutathione conjugation of the alpha-bromoisovaleric acid enantiomers in the rat in vivo and its stereoselectivity. Pharmacokinetics of biliary and urinary excretion of the glutathione conjugate and the mercapturate. AB - The glutathione (GSH) conjugation of (R)-and (S)-alpha-bromoisovaleric acid (BI) in the rat in vivo, and its stereoselectivity, have been characterized. After administration of racemic [1-14C]BI two radioactive metabolites were found in bile: only one of the possible diastereomeric BI-GSH conjugates, (R)-I-S-G (35 +/ 2% of the dose), and an unidentified metabolite "X" (6 +/- 1%). In urine, only one of the possible BI-mercapturates, (R)-I-S-MA (14 +/- 1%), minor unidentified polar metabolites (5 +/- 1%) and unchanged BI (13 +/- 2%) were excreted. When (R) or (S)-BI were administered separately, the same metabolites were found. However, a ten-fold difference in excretion half lives of the biliary metabolites was observed following (S)-and (R)-BI administration, (S)-BI being more rapidly excreted. The excretion of the mercapturate in urine shows the same difference in excretion rate: its half life after administration of (R)-BI was more than 10 times longer than after a dose of (S)-BI. More of the dose of (S)-BI was excreted after 5 hr in bile and urine: 58% and 23% respectively for (S)- and (R)-BI. Therefore, a pronounced stereoselectivity in GSH conjugation exists for the (R) and (S) enantiomers of BI in the rat in vivo, which is a major determinant of their pharmacokinetics. The results suggest that (slow) inversion of the chiral centre of BI occurred in the rat in vivo. PMID- 2597179 TI - Metabolism of N-acetyl-L-cysteine. Some structural requirements for the deacetylation and consequences for the oral bioavailability. AB - Rat liver, lung and intestine homogenates deacetylated N-acetyl-L-cysteine. Nearly stoichiometric amounts of L-cysteine were recovered. In rat liver, the enzyme activity was associated with the cytosolic fraction. Liver cytosol was much less active. N-Acetyl-D-cysteine or the disulphide of N-acetyl-L-cysteine were not deacetylated or in other ways consumed in vitro. Isolated, perfused rat liver did not retain or metabolize N-acetyl-L-cysteine to any measurable extent during single-pass experiments. N-Acetyl-L-cysteine or N-acetyl-D-cysteine were injected into a ligated segment of rat intestine in situ. After 1 hr 2% of the L isomer and 35% of the D-isomer remained in the intestinal lumen. Systemic plasma levels were less than 3 microM of the L-form and congruent to 40 microM of the D form. We conclude that deacetylation in the intestinal mucosa and possibly in the intestinal lumen is the major factor determining the low oral bioavailability of N-acetyl-L-cysteine. The deacetylation is discussed on the basis of the subcellular localization and the structural requirement of the reaction. PMID- 2597180 TI - Catalytic effect of serum albumin on the o-rearrangement of N-sulfooxy-2 acetylaminofluorene, a potential hepatocarcinogen in the rat, to nonmutagenic sulfuric acid esters of o-amidofluorenols. AB - Bovine serum albumin (BSA) catalyzes the o-rearrangement of the reactive electrophile, N-sulfooxy-2-acetylaminofluorene (NSF), a potential ultimate hepatocarcinogen in the rat, to the nonmutagenic sulfuric acid esters of 1- and 3 hydroxy-2-acetylaminofluorene. Conversion of NSF was proportional to BSA concentrations ranging from 0.25 to approximately 4 mg BSA/ml incubation mixture. At concentrations greater than or equal to 5 mg BSA/ml, approximately 90% of NSF was converted to the sulfuric acid esters of the o-amidofluorenols. Human serum albumin (HSA) likewise catalyzed the o-rearrangement of NSF. However, the catalytic activity of HSA was only approximately 50% of the activity of BSA. The catalytic effect of BSA was abolished by heat denaturation. However, it was not changed by dialysis or by anion exchange chromatography. These observations indicated that the catalytic effect requires intactness of the tertiary structure of BSA and is not due to a contaminant(s) of low or high molecular weight. There were no differences in the catalytic activity of three separate fractions of chromatographed BSA, suggesting that the catalytic activity is associated with the entire BSA molecule. In contrast to serum albumin, gamma-globulin (bovine or human) did not catalyze the o-rearrangement of NSF. The solvolytic degradation of NSF to 4-hydroxy-2-acetylaminofluorene, a major reaction in the absence of BSA, occurred only to a minor extent in the presence of BSA. These data indicated that the BSA-catalyzed o-rearrangement determines the rates of concurrent reactions involved in the degradation of NSF. BSA and HSA did not catalyze the o rearrangement of N-acetoxy-2-acetylaminofluorene (N-OAC-2-AAF), the acetate ester of N-hydroxy-2-acetylaminofluorene (N-OH-2-AAF), to the acetic acid esters of the o-amidofluorenols. These findings suggest that the albumin-catalyzed o rearrangement occurs preferentially with esters of fluorenylhydroxamic acids that readily ionize in aqueous media. PMID- 2597181 TI - Effect of toluene on rat synaptosomal phospholipid methylation and membrane fluidity. AB - This study investigated the effects of toluene (1 g/kg, 1 hr, i.p.) on rat synaptosomal phospholipid methylation (PLM), phospholipid composition, and membrane fluidity. Toluene significantly decreased basal PLM (35%) in studies using [3H]methionine [( 3H]Met) as the methyl donor; this was reflected by similar decreases in phosphatidylmonomethylethanolamine (PME) (30%). No effects were observed in either PLM reactions that used [3H]adenosylmethionine [( 3H]AdoMet) as methyl donor, or AdoMet synthetase, suggesting that toluene preferentially affects PLM reactions that derive methyl groups from [3H]Met. Also, toluene decreased synaptosomal phosphatidylethanolamine (PE) (24%), the initial substrate for PLM, and the addition of PE back to PE-depleted synaptosomes restored methyltransferase activity. Agonist-stimulated PLM using norepinephrine (NE) demonstrated that agonist-receptor coupling returned PLM to control values in synaptosomes from toluene-treated rats. NE-stimulated PLM was also blocked by propranolol (PRO), suggesting a role for toluene in receptor mediated events. Membrane fluidity studies demonstrated that in vivo administration of toluene increased the outer synaptosomal membrane fluidity, whereas in vitro administration of toluene had no effect. Our observations support a positive relationship between increased PLM activity and increased outer, not core, membrane fluidity. These data demonstrate that specific toluene phospholipid interactions occur in synaptosomes, resulting in altered membrane composition, function and fluidity. PMID- 2597182 TI - A simple method for the correction of biliary excretion curves distorted by the biliary dead space. AB - Biliary solute concentrations measured at the tip of the cannula suffer a delay with respect to bile flow due to the transit time through the biliary tree volume. This study proposes a simple method, which is valid under variable bile flow conditions, to correct the distortion introduced by the biliary tree volume on the kinetic curves of the biliary excretion rate. The biliary transit time (tt) was calculated as the time needed to excrete a bile volume equal to the biliary tree volume by means of the interpolation of biliary cumulative volume versus time curves. Such tt permits one to estimate the canalicular concentration at time t, interpolating the biliary concentration curves at time t-tt. The product between the estimated canalicular concentration and the bile flow allows the calculation of the corrected biliary excretion rate. This method was evaluated by a comparison between biliary excretion rate curves of [14C]taurocholate [( 14C]TC) injected as a bolus under basal and sodium dehydrocholate (DHC)-induced choleresis conditions. Since the canalicular excretion rate of [14C]TC is considered independent of bile flow, the significant differences observed in its excretion kinetics under both conditions were attributed to distortion due to the biliary tree volume. After the correction, both curves showed a significant overlapping. This result indicates that the method improves the time-course representation of canalicular events in biliary excretion kinetic studies. PMID- 2597183 TI - Pregnancy-associated changes in renal metallothionein concentration and plasma distributions of metals. AB - Pregnancy-associated changes in concentrations and distributions of selected essential elements were examined in the blood and tissues of rats. Concentrations of copper (Cu) and zinc (Zn) in the kidneys of dams significantly decreased with gestational age and recovered after delivery. Distribution profiles of multi elements in the supernatant of the kidneys indicated that Cu and Zn bound to metallothionein decreased with gestational age without affecting their distributions to other components. Although concentrations of Cu and Zn in the liver did not show significant changes during gestational period, Zn bound to metallothionein decreased with gestational age. Plasma concentrations of Cu, iron, phosphorus, sulfur, Zn and other elements were altered by the physiological change, some of those chemical forms being assigned. PMID- 2597185 TI - A new proposal for the mechanism of cyclosporine A nephrotoxicity. Inhibition of renal microsomal protein chain elongation following in vivo cyclosporine A. AB - In this paper, we report experiments examining the effect of cyclosporine A on "run-off" translation in microsomes isolated from tissues of Sprague-Dawley rats. In microsomes isolated from rat brain, kidney and thymus, cyclosporine A added in vitro in concentrations of up to 100 micrograms/ml did not reduce [3H]L-leucine incorporation relative to controls. A small dose-dependent reduction in [3H]leucine incorporation was observed in microsomes isolated from rat liver when cyclosporine A was added in high concentrations (5 and 6% at 25 and 100 micrograms/ml). However, when cyclosporine A was injected at 50 mg/kg/day for 10 days, [3H]L-leucine incorporation was inhibited 99.9% in microsomes isolated from kidney. The oral administration of cyclosporine A at 50 mg/kg/day for 6-10 days produced a 75% inhibition of incorporation by isolated renal microsomes. These changes were observed in the absence of measurable reductions in "run-off" transcription measured as [3H]UTP incorporation by renal nuclei exposed to cyclosporine A in concentrations of up to 100 micrograms/ml in vitro or isolated from animals given oral cyclosporine A at 50 mg/kg/day for 6 days. Cross-over experiments were performed using microsomes and microsomal supernatant fractions (cell saps) from tissues of animals treated with cyclosporine A and control vehicle. Renal cell sap from cyclosporine A treated animals inhibited [3H]L leucine incorporation by microsomes isolated from the kidneys or other tissues of animals treated with control vehicle. These experiments demonstrated that a translation inhibitor was present in the cell sap of cyclosporine A treated animals which could directly block translation elongation in microsomes from control animals. When renal cell sap from both control and cyclosporine A treated animals was added to control microsomes, inhibition was still prominent, suggesting the presence of an inhibitor rather than the absence of an elongation factor. Oral administration of cyclosporine A at 50 mg/kg/day for 6 days depressed renal microsomal [3H]L-leucine incorporation equally in male and female rats to 25% of control. The dose-response relationship for microsomal protein synthesis inhibition after 6 days of oral cyclosporine A administration was: 5 mg/kg, 73.7% of control; 10 mg/kg, 64.1% of control; 25 mg/kg, 54.9% of control and 50 mg/kg, 24.1% of control. Renal microsomal protein synthesis following oral cyclosporine A at 50 mg/kg/day was reduced to 54% of control by day 2 and was maximally inhibited at 25-30% of control by day 4.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2597184 TI - Comparative activity of anthracycline 13-dihydrometabolites against rat glioblastoma cells in culture. AB - We have studied the growth inhibition, DNA synthesis inhibition and cell incorporation of five 13-dihydrometabolites of anthracyclines in a model of doxorubicin-sensitive and -resistant rat C6 glioblastoma cells. These compounds were major metabolites for doxorubicin, epirubicin, daunorubicin, idarubicin and the new anthracycline 4'-deoxy-4'-iododoxorubicin and are known to be present in appreciable amounts in the plasma of patients treated with these drugs. We have shown that in vitro growth inhibition in sensitive cells was either much lower than that of the parent drug (doxorubicinol, epirubicinol, daunorubicinol), or similar to it (idarubicinol, 4'-iodoxorubicinol). In resistant cells, growth inhibition was about 100 times lower than in wild cells, and was always lower than that of the parent anthracycline. DNA synthesis inhibition occurred in sensitive cells for doses about 100 times higher than those required for growth inhibition, but in resistant cells, similar doses provided growth inhibition and DNA synthesis inhibition. Metabolite incorporation was always lower than that of the corresponding parent anthracycline; it was greatly reduced in resistant cells as compared to sensitive ones. The calculated intracellular concentrations obtained for the same growth inhibition are higher in resistant cells than in sensitive cells; in contrast, the calculated intracellular concentrations obtained for the same DNA synthesis inhibition are similar in resistant and sensitive cells, and similar for all the metabolites studied. These results suggest that the amount of drug incorporated is primarily responsible for DNA synthesis inhibition, which is directly correlated to growth inhibition in resistant cells, but not in sensitive cells. PMID- 2597186 TI - Dimethyldisulfide formation during trichloromethyl radical attack on methionine. PMID- 2597187 TI - The influence of acute phenytoin administration on biotransformation and lipid peroxidation in the liver of rats of different ages. PMID- 2597188 TI - Quantitative assessment of enzyme induction by peroxisome proliferators and application to determination of effects on triglyceride biosynthesis in primary cultures of rat hepatocytes. AB - Potencies for the induction of peroxisomal fatty acyl-CoA oxidase (FACO) and microsomal laurate hydroxylase (LH) were determined for clofibric acid (CPIB), ciprofibrate (Cipro) and gemfibrozil (Gem) in primary cultures of rat hepatocytes based on complete concentration-response analysis and determination of theoretical maximum inductive responses for Cipro. CPIB and Cipro each induced FACO and LH in a concentration-dependent manner. Scatchard analysis of the data allowed calculation of EC50 values (mM) of 0.82 and 0.028 (for FACO) and 0.22 and 0.0081 (for LH) for CPIB and Cipro respectively. The EC50 ratios (CPIB/Cipro) were identical (29-fold) for induction of FACO and LH, supporting the concept that these enzymes are induced by CPIB and Cipro through a common mechanism. By comparison, Gem was relatively ineffective as an inducer of FACO and LH. Furthermore, Gem did not antagonize Cipro-mediated enzyme inductions, suggesting that Gem is a peroxisome proliferator of low potency rather than a partial agonist. Based on the potency and time-course profiles observed for induction of FACO and LH, the effects of CPIB, Cipro and Gem on triglyceride (TG) biosynthesis were determined in the cultured rat hepatocytes. Conditions of maximal FACO and LH induction by the drugs did not result in inhibition of TG biosynthesis in the cells. These results support the in vivo evidence which indicates that FACO and LH induction are not causally linked to the hypotriglyceridemic actions of peroxisome proliferating drugs. PMID- 2597189 TI - Structural requirement of monophosphates for inhibition of Na+-Pi cotransport in renal brush border membrane. AB - Using the chemical structural analogs of phosphonoacetic acid (PAA) and related phosphonate compounds, we investigated which structural features are required for competitive inhibition of Na+-Pi cotransport in rat renal cortical brush border membrane (BBM) vesicles (BBMV). The effects of compounds on [Nao+ greater than Nai+]-gradient-dependent 32Pi uptake by BBMV were examined using various inhibitor-to-32Pi concentration ratios in the transport assay medium. The replacement of a phosphono-group with an arsono-group in PAA, or the substitution of a carboxylic group in PAA by an amino or hydroxyl group, totally abolished the inhibitory action on Na+-Pi cotransport. Decreased electronegativity of carboxyl in PAA by coupling with hydrazine or hydroxylamine lowered the inhibitory potenty of PAA. Substitution of H at the alpha-carbon of PAA with ethyl or p-Cl-phenyl groups completely abolished the inhibitory activity, whereas alpha-halogenation with Br greatly increased the inhibitory potency of PAA, close to that of phosphonoformic acid (PFA). The inhibition by all the active tested monophosphates was strictly competitive. The tested compounds displaced [14C]PFA pre-bound onto BBMV in the presence of 100 mM NaCl. The ability of monophosphates to inhibit Na+-Pi cotransport across BBM and the binding of [14C]PFA were closely correlated (r = 0.925; P greater than 0.001). These results show that: (a) strong electronegativity at both ends of the PAA molecule is needed for inhibitory action, (b) an alpha-aliphatic or aromatic substituent at the alpha-carbon probably hinders the access of the inhibitor to the Pi-binding site of the Na+-Pi cotransporter in BBM, whereas (c) an alpha-electrophilic substituent--Br- enhances the inhibitory potency of PAA. The tested compounds inhibited Na+-Pi cotransport by binding, in the presence of Na+, on the same site on the luminal surface of BBM as did PFA and, by extension, Pi. PMID- 2597190 TI - A 62 kDa protein is photoaffinity labelled by [3H]felodipine in vascular smooth muscle, but not in cardiac and skeletal muscle. AB - Irradiation of a cytosolic fraction from vascular smooth muscle in the presence of [3H]felodipine resulted in the labelling of a protein with an apparent molecular weight of 62 kDa. The labelling was seen on UV-irradiation at 360 nm, but not at 254, 278 or at wavelengths above 410 nm. The photolabelling was enhanced in the absence of oxygen. In cytosolic fractions prepared from porcine liver, cardiac and skeletal muscle no photoaffinity labelling of proteins between 90 and 45 kDa could be demonstrated. The results suggest that felodipine is a photoaffinity ligand and that felodipine binds to a soluble protein present in vascular smooth muscle but not in the other tissues tested. PMID- 2597191 TI - In vivo oxidative cleavage of a pyridine-carboxylic acid ester metabolite of nifedipine. AB - The pharmacokinetics of the primary pyridine metabolite of nifedipine (2,6 dimethyl-4-(2-nitrophenyl)-3,5-pyridinecarboxylic acid dimethylester) (M-0) and its [2H6]dimethylester analog ([2H6]M-0) were studied in male rats. A large, 5.8 fold deuterium isotope effect for the formation clearance of the monomethylester (M-1) was observed, which is strongly indicative for an oxidative reaction mechanism involving the abstraction of a hydrogen atom, presumably by cytochrome P-450. M-0 exhibited a high systemic blood clearance (104 +/- 27 ml/min/kg) (mean +/- SD) which was not significantly influenced by deuterium substitution (125 +/- 13 ml/min/kg). Its systemic clearance is presumably flow limited, and extrahepatic metabolism can be anticipated. The major metabolic pathway for M-0 in male rats seems to be a direct oxidation at the 2-methyl position and subsequently a rapid conversion of the unstable 2-hydroxymethyl-dimethylester to the lactone of the monomethylester (M-2), as has been shown by others in vitro. Non-oxidative ester cleavage of M-0 in our rats was negligible. Deuterium substitution of M-0 at the ester methyl groups induced "metabolic switching" in favor of the direct oxidation of M-0 to M-2. PMID- 2597192 TI - Organic solvents as modifiers of aldrin epoxidase in reconstituted monooxygenase systems and in microsomes. AB - To examine the response of individual cytochrome P-450 species catalysing the epoxidation of aldrin (Wolff T and Guengerich FP, Biochem Pharmacol 36: 2581 2588, 1987), monooxygenase systems reconstituted from these species were assayed in the presence of 5% (v/v) = 0.87 M ethanol. The activity of cytochromes P-450PB B and P-450PB-D, two enzymes inducible by phenobarbital was increased seven-fold. The activity of two other P-450 enzymes purified from these animals was either inhibited by 50%, as observed for cytochrome P-450PB-C or remained unchanged, as noted with cytochrome P-450PCN-E. Two P-450 enzymes purified from untreated rats, cytochromes P-450UT-F and P-450UT-H, showed an inhibition by 50 and 20%, respectively, while the activity of cytochrome P-450UT-A was slightly increased by 50%. Indirect evidence that solvents enhance aldrin epoxidation by interacting with the hemoprotein was obtained by the finding that ethanol stimulated the activity of cytochrome P-450PB-B already, before addition of the lipid component, L-alpha-1,2-dilauroyl-sn-glycero-3-phosphocholine. The Km of cytochrome P-450PB-B for NADPH cytochrome P-450 reductase was not altered by ethanol indicating that the interaction between the two enzymes was not affected by the solvent. Other results indicate that the stimulatory solvent binds to a site, apart from the type I or type II binding site. The potency of various hydrophylic solvents to modify aldrin epoxidase activity was assayed in microsomes of rats pretreated with phenobarbital and of untreated male rats. Ethanol, n-propranol, n-butanol, acetone and tetrahydrofuran enhanced enzyme activity of phenobarbital pretreated rats to a maximal extent of two-fold and, at similar concentrations, inhibited the enzyme activity of untreated rats by 50%. The potency of these solvents correlated with their lipophilicity. Methanol and dimethylsulfoxide only slightly modified the activity of induced and noninduced animals. In the presence of 0.5 M n-propranol as the modifying agent, microsomal epoxidase activity of rats pretreated with pregnenolone-16 alpha-carbonitrile, dexamethasone, 3 methylcholanthrene and of control rats was inhibited by 60-80%, whereas the activity of animals pretreated with phenobarbital, DDT, or the polychlorinated biphenyl mixture, Clophen A 50, was stimulated between two- and three-fold. The results reveal that organic solvents frequently used to dissolve monooxygenase substrates may considerably modify the activity of cytochrome P-450 dependent reactions, in particular when purified enzymes are assayed. PMID- 2597193 TI - Extracellular calcium alleviates cell toxicity due to hepatotoxins that induce lipid peroxidation, but has no effect on toxins that do not cause lipid peroxidation. A study in isolated rat hepatocytes. AB - The effect of extracellular calcium on cell death, induced by hepatotoxins that induce lipid peroxidation [diethyl maleate (DEM), allyl alcohol (AA) and bromoisovalerylurea (BIU)] and hepatotoxins that do not induce lipid peroxidation [disulfiram (DSF), N-hydroxy-2-acetyl-aminofluorene (N-OH-AAF) and tetrahydroaminoacridine (THA)] was studied in freshly isolated rat hepatocytes. Extracellular calcium strongly delayed the onset of toxicity of DEM, AA and BIU as detected by lipid peroxidation, depletion of free protein thiol groups and cell death. This protective effect of calcium was decreased at higher concentrations of the toxic compounds. In contrast, no effect of calcium was observed on toxicity induced in the absence of lipid peroxidation by DSF, N-OH AAF and THA. Addition of calcium was also without effect on the protein thiol depletion. These results indicate that calcium only alleviates cytotoxicity which is induced by thiol depletion resulting from lipid peroxidation. Cytotoxicity as a result of protein thiol depletion through disulfide formation is not affected by extracellular calcium. PMID- 2597194 TI - Sulfation in male reproductive organs. Bull and boar testis phenol sulfotransferases. AB - Phenol sulfotransferases (PST) from bull and boar testis were partially purified and characterized. A single form of PST adsorbed on DEAE-cellulose was found in the bull testis, whereas from boar testis two different peaks of PST activity were separated. The bull testis PST and both boar testis enzymes were active with p-nitrophenol and adrenalin. They all showed higher affinity to pNP than to adrenalin and were inhibited by these substrates at higher concentrations. Their optimal pH was at 8.5. Bull testis PST and boar PST II which were adsorbed on DEAE-cellulose were thermostable, whereas boar PST I was thermolabile. Those three PST forms differed in sensitivity to 2,6-dichloro-4-nitrophenol (DCNP), N ethyl maleimide (NEM), iodoacetamide (IAA) and phenylglyoxal (PG). Bull and boar PST II were more rapidly inactivated in the presence of DCNP than boar PST I. In the presence of NEM, the--SH groups reagent, the bull phenol sulfotransferase and boar PST I lost their activity, whereas the activity of boar PST increased. Also iodoacetamide, another--SH group modificator, raised boar PST II activity and decreased boar PST I activity. DTT, which protects thiol groups, had an opposite effect on the enzymes studied than NEM. Phenylglyoxal, a reagent specific for arginine residues inhibited bull testis PST and both boar phenol sulfotransferases. Substrate protection experiments were also performed to determine the localization of reactive groups in bull and boar testis phenol sulfotransferases. PMID- 2597195 TI - 5-Hydroxytryptamine2 (5-HT2) structure-function relationships of the nitro and amino phenylpiperazines on intact human platelets. AB - Nitro and amino phenylpiperazines were synthesized to study the agonist and antagonist activities of the phenylpiperazines at the human platelet 5 hydroxytryptamine2 (5-HT2) receptor. Amplification of ADP-induced aggregation and binding competition experiments with [3H]ketanserin were used to evaluate receptor interactions in this system. All the monosubstituted phenylpiperazines were antagonists despite the wide variation in electronic and hydrophobic properties. The parent compound, unsubstituted phenylpiperazine (PP), had the lowest affinity for the [3H]ketanserin binding site. The intensely electron withdrawing NO2 substituent increased binding affinity at all ring positions and this activity correlated with antagonist potency in platelet aggregation studies (rank order: 4-NO2-PP greater than 3-NO2-PP greater than 2-NO2-PP). NH2 substitution decreased binding affinity at the 4- and 2-positions compared with the analogous NO2 substituted compounds; however, evaluation of NH2-PP antagonist potency in aggregation studies was complicated due to slow association with the receptor. To compare the activities of the phenylpiperazines at other 5-HT sites, binding competition experiments were performed using [3H]5-HT in bovine brain membranes. The rank order of the affinities for the NO2 substituted compounds was distinctly different from that determined with platelets, reflecting the heterogeneous composition of 5-HT receptor subtypes in the brain membrane preparations. The platelet aggregation experiments demonstrated that marked alteration of the electronic and hydrophobic properties of phenylpiperazine by ring substitution did not impart 5-HT2 agonist activity. By contrast, 5-HT2 antagonist activity appeared to be enhanced markedly by electron-withdrawing resonance effects which decreased the electron density at the 1'-piperazine nitrogen. This enhancement appeared to be specific for the 5-HT2 receptor subtype. PMID- 2597196 TI - Deuterium isotope effect of phenelzine on the inhibition of rat liver mitochondrial monoamine oxidase activity. AB - Phenelzine is a suicide monoamine oxidase (MAO) inhibitor with antidepressant properties. The present study compares the inhibition of rat liver mitochondrial MAO by phenelzine and 1,1-dideuterated phenelzine and the metabolism of these drugs by that enzyme. Phenylacetaldehyde, which was measured by a high performance liquid chromatographic procedure, was found to be the major metabolite of phenelzine after incubation with MAO. The time-courses of aldehyde formation were non-linear due to the time-dependent inhibition of MAO. The reaction rate was reduced substantially when the hydrogen atom in the 1-carbon position was replaced by deuterium. The VH/VD value was 3.1, indicating a primary isotope effect. Such a substitution of deuterium in the phenelzine molecule did not affect significantly the initial reversible inhibition of MAO, which was determined by comparison of their Ki values. The irreversible inhibition, as estimated from IC50 values, however, was potentiated substantially by deuteration. These results support the notion that the irreversible inhibition of MAO activity by phenelzine proceeds via a phenylethyldiazene intermediate, which reacts with the enzyme to form a covalent adduct. An alternative pathway involving hydrogen abstraction from carbon-1 of phenelzine or via rearrangement of the diazine on the enzyme surface could occur to form a phenylethylidene hydrazine intermediate which would subsequently be hydrolyzed to phenylacetaldehyde. The reduction in the rate of phenylethylidene hydrazine formation due to the isotope effect could lead to the accumulation of phenylethyldiazene intermediate and thus potentiate the inhibition of MAO activity. PMID- 2597197 TI - Interaction of the peroxidase-derived metabolite of mitoxantrone with nucleic acids. Evidence for covalent binding of 14C-labeled drug. AB - The antitumor agent mitoxantrone undergoes horseradish peroxidase-catalyzed oxidation by hydrogen peroxide to an identifiable cyclic metabolite which is a substituted hexahydronaphtho[2,3-f]-quinoxaline-7,12-dione. Binding of mitoxantrone to DNA inhibited enzymatic oxidation of the drug. The metabolite of mitoxantrone, derived from the action of the HRP/H2O2 system on the drug, bound non-covalently to DNA oligomers. Spectrophotometric analyses of such complexes showed formation of a new, blue-shifted, metachromatic absorption band which was observed when the DNA base pair to drug ratio was close to 1. Measurements of DNA unwinding angles suggest that the metabolite, in contrast to mitoxantrone, did not intercalate but rather bound externally to DNA. Experiments with 14C-labeled mitoxantrone confirmed that peroxidase-activated drug binds covalently to DNA. PMID- 2597198 TI - Generation of extracellular ATP in blood and its mediated inhibition of host weight loss in tumor-bearing mice. AB - Intraperitoneal injections of adenosine 5'-monophosphate (AMP) or adenosine 5' triphosphate (ATP), but not of adenosine, inorganic phosphate or pyrophosphate, were shown to inhibit tumor growth and host weight loss in tumor-bearing murine hosts. The inhibition of tumor growth and host weight loss did not exhibit a cause-effect relationship, though both were mediated through expansion of red blood cell (RBC) ATP pools which were promoted by administered adenine nucleotides. We then demonstrated that expansion of RBC ATP pools was preceded by expansion of liver ATP pools and that the adenosine precursor for this type of enhanced RBC ATP synthesis originated in the turnover of expanded liver ATP pools. Although adenosine, which is the primary catabolic product of ATP in the peritoneal cavity or the systemic circulation, was sufficient to yield an expansion of mouse liver ATP pools in vivo, external phosphate was required for the subsequent expansion of RBC ATP pools, which in turn produced elevated extracellular (blood plasma) ATP levels. The anticancer activities which correlate with the elevated blood plasma ATP concentrations are proposed to be the result of direct action of extracellular ATP on the tumor and host tissues. PMID- 2597199 TI - Relevance of the chemical charge of rhodamine dyes to multiple drug resistance. AB - Previously, we have shown that multiple drug resistant (MDR) Friend leukemia cells (FLC) are cross-resistant to the positively-charged dye, Rhodamine 123 (Rho 123), and that this resistance can be reversed by verapamil (VER). In the present study we used two zwitterionic rhodamine analogs, Rhodamine 116 and Rhodamine 110, and another positively-charged analog, Rhodamine 6G, to determine whether drug accumulation, resistance and modulation were affected by changes in the charge of these compounds. While there was no differential sensitivity between sensitive and resistant FLC to zwitterionic rhodamines, there was marked differential toxicity between these cell types for the positively-charged analogs. The IC50 values were 1000- and 100-fold greater in resistant than in sensitive cells for Rho 123 and Rho 6G respectively. Intracellular drug accumulation was significantly higher in sensitive as compared to resistant cells for both Rho 123 and Rho 6G, but little difference in drug uptake between these two cell types was observed for Rho 110 and Rho 116. It was also found that the intracellular to extracellular ratio of the positively-charged compounds was greater than unity in both sensitive and resistant cells whereas for the zwitterionic analogs this ratio was less than 1. Furthermore, this ratio of drug uptake was found to be significantly higher for Rho 6G than for Rho 123, which correlated with the high oil:water partition coefficient of Rho 6G (115.6). In MDR cells, verapamil increased Rho 123 and Rho 6G accumulation by 9.4- and 8.6 fold respectively. In addition, IC50 values in resistant cells were reduced greater than 100-fold for Rho 6G and greater than 1000-fold for Rho 123 in the presence of 10 micrograms/ml of verapamil. In contrast, less than 2-fold reduction of IC50 values for both of the zwitterionic analogs could be obtained under the same conditions. These results indicate that the chemical charge of rhodamines plays an important role in their differential accumulation, cytotoxicity and sensitivity to modulators such as verapamil, in sensitive and multi-drug resistant cells. The data also suggest that increased lipophilicity of the positively-charged rhodamines may increase their ability to accumulate in, and subsequently kill, MDR cells. PMID- 2597200 TI - Persistent intracellular binding of mitoxantrone in a human colon carcinoma cell line. AB - Incubation of human carcinoma cells with mitoxantrone resulted in an intracellular distribution of the drug into cytoplasmic, nuclear and cytoskeletal compartments occurring within 1 min of drug treatment. Incubation of the cells in drug-free medium resulted in an efflux of the drug such that 80% of the intracellular drug was eliminated from the cells by 72 hr. Approximately 20% of the initial intracellular drug concentration remained in the cells after the drug had been removed from the medium. The majority of the persistent intracellular drug was associated with soluble cytoplasmic proteins and fractions enriched in nucleic acid. Approximately 10% of the persistent drug binding was associated with cellular structures that had been depleted of soluble cytoplasmic protein and nucleic acid. During the persistent drug binding, the cells enlarged at least 2-fold as determined by microscopic examination. An increasing percentage of the cells was also observed to contain a DNA content consistent with a G2 cell cycle arrest. Taken together, these data suggest that the persistent intracellular binding of mitoxantrone results in a G2 cell cycle arrest and cellular damage. PMID- 2597201 TI - The metabolism of sulfite in liver. Stimulation of sulfate conjugation and effects on paracetamol and allyl alcohol toxicity. AB - Sulfite is rapidly oxidized to sulfate in the liver. This was shown both in isolated rat hepatocytes and isolated perfused liver. In addition sulfite treatment resulted in release of GSH originating probably from low molecular disulfides such as GSSG and/or mixed disulfides between GSH and protein sulfhydryl groups. Sulfite was demonstrated to be an efficient precursor for sulfate conjugation. This was demonstrated using paracetamol as a substrate. Sulfite was even more efficient in supplying sulfate for sulfate conjugation than inorganic sulfate. Sulfite was furthermore shown to be protective against the toxicity of both N-acetyl-p-benzoquinone imine (NAPQI), the reactive paracetamol metabolite, and acrolein, a reactive aldehyde which is a metabolite of allyl alcohol. This protection is most likely due to direct reaction between sulfite and these reactive metabolites in a manner similar to that occurring with GSH and other thiols. When NAPQI and acrolein were generated intracellularly in isolated hepatocytes from paracetamol and allyl alcohol, respectively, toxicity was also expressed. In this case sulfite only protected against allyl alcohol induced toxicity and not against paracetamol induced toxicity. The reason for this discrepancy is not clear but may depend on factors such as site of generation of the reactive metabolite or the reactivity of the reactive metabolite. PMID- 2597202 TI - Interaction of D, L-erythro- and D,L-threo-gamma-fluoromethotrexate with human leukemia cell dihydrofolate reductase. AB - Gamma-fluoromethotrexate (FMTX) is a poorly glutamylated mimic of the anti-cancer drug methotrexate (MTX) which is useful in studies of the roles of MTX poly-gamma glutamates. A second chiral center occurs at C-4 of the 4-fluoroglutamate used to synthesize FMTX and, as a consequence, FMTX occurs as both D,L-erythro and D,L threo diastereomers. The interaction of both diastereomers with intracellular dihydrofolate reductase has been examined in the human leukemia cell line CCRF CEM, using a centrifugal column technique. Measurements of the rate at which radiolabel was displaced from [3H]MTX-saturated dihydrofolate reductase following suspension of the cells in unlabeled drug indicated that MTX and the erythro isomer of FMTX gave essentially the same rate of displacement; the rate of displacement by the threo isomer of FMTX was slower, but the interpretation of these data was ambiguous since the rate of transport of threo-FMTX may have been limiting. In reciprocal experiments in which dihydrofolate reductase was saturated with [3H]erythro-FMTX, the erythro isomer and MTX again behaved equivalently in terms of displacement. When dihydrofolate reductase was saturated with [3H]threo-FMTX, the radiolabel was clearly displaced at a much faster rate than either other radiolabel regardless of whether the displacing agent was MTX or the isomer. These results indicate a distinct stereospecificity for interaction of inhibitor with dihydrofolate reductase in which the threo isomer has a faster off-rate. Of the two FMTX diastereomers, the erythro isomer thus most closely mimics the properties of MTX. PMID- 2597203 TI - Effects of intermediary metabolites and electron transport inhibitors on action of chloroquine on Brugia pahangi and Onchocerca volvulus. AB - We examined the possibility that chloroquine is interfering with aerobic energy generating processes in the adult filarial parasites, Brugia pahangi and Onchocerca volvulus. Using motility of these parasites as an assay of drug effect, we found that micromolar concentrations of chloroquine caused significant paralysis, but only in alkaline medium (pH 8.4). The addition of 12 mM glutamine or 10 mM albizziin to the medium completely antagonized drug-induced paralysis. In addition, in B. pahangi, all of the tricarboxylic acid cycle intermediates (10 mM) except citrate and pyruvate antagonized the effect of chloroquine on motility; in O. volvulus, oxaloacetate as well as glutamine inhibited the effect of the drug. The effect of chloroquine on both parasites was enhanced when it was used in combination with 10 microM acivicin, a glutamine antimetabolite. Here motility of B. pahangi was reduced significantly within 24-48 hr at acidic (6.8) neutral (7.4) and alkaline (8.4) pH. This effect was partially reversible by glutamine (12 mM). Motility of O. volvulus was reduced to near zero within 4 hr with this drug combination. Antimycin A and rotenone, both electron transport inhibitors, also synergized with chloroquine at any pH to produce paralysis in B. pahangi. The effects of the rotenone and chloroquine combination were reversed in the presence of 10 mM succinate. However, glutamine (12 mM) was unable to antagonize the effects of chloroquine plus antimycin A on the motility of B. pahangi. These findings suggest that chloroquine may be inhibiting aerobic energy metabolism in the filariae, possibly at the level of electron transport. Furthermore, since chloroquine is well-tolerated but only weakly filaricidal in vivo, the data indicate that use of this drug in combination with other inhibitors of aerobic energy metabolism may be a chemotherapeutically useful approach to the treatment of filariases. PMID- 2597204 TI - Lack of effect of chronic aspartame ingestion on aminergic receptors in rat brain. PMID- 2597206 TI - Antiperoxidant effects of dihydropyridine calcium antagonists. PMID- 2597205 TI - Uroporphyria caused by acetone and 5-aminolevulinic acid in iron-loaded mice. PMID- 2597207 TI - Demonstration of a new antinuclear antibody (anti-RA33) that is highly specific for rheumatoid arthritis. AB - Using immunoblot analysis with soluble nuclear extracts from HeLa cells, we identified autoantibodies to an antigen with a molecular weight of approximately 33,000 in 36% of 95 sera from rheumatoid arthritis patients, but in only 1 of 170 controls. The antigen, termed RA33, was resistant to DNase and RNase digestion but sensitive to proteinase K treatment. There was no discernible relation to other autoantibodies. Thus, this newly described autoantibody appears to be highly specific for rheumatoid arthritis. PMID- 2597208 TI - Interleukin-1-inhibitory IgG in sera from some patients with rheumatoid arthritis. AB - Inhibition of interleukin-1 alpha (IL-1 alpha) activity was detected in 7 of 41 serum samples from patients with rheumatoid arthritis (RA). These 7 sera inhibited not only IL-1 alpha-induced endothelial cell adherence to neutrophils, but also IL-1 beta-induced endothelial cell adherence, although to a lesser extent. These sera showed no influence on tumor necrosis factor-induced endothelial cell adherence. No inhibitory activity was found in 40 sera from normal control subjects. Studies to further examine these effects included gel filtration analysis of 2 of the RA sera. The inhibitory activity was eluted near Mr 158 kd and above Mr 250 kd. Analysis by protein A affinity chromatography showed that IL-1-inhibitory activity was present in protein A-binding fractions. Purified IgG (by DE-52 column chromatography) from RA patients was found to be as potent an inhibitor as the protein A-binding fractions, which suggests that the major inhibitory activity in RA sera is attributable to IgG molecules. These purified IgG molecules also inhibited IL-1-induced proliferation of mouse thymocytes but did not influence IL-2-dependent proliferation of the CTLL-2 murine T cell line. The 7 patients whose sera showed IL-1-inhibitory activity had mild RA and low titers of rheumatoid factor. The findings, taken together, suggest a possible regulatory role of IL-1-inhibitory IgG in RA disease activity. PMID- 2597209 TI - Arthritis in nursing home residents. A validation of its prevalence and examination of its impact on institutionalization and functional status. AB - We studied nursing home residents to validate the method used in national surveys for estimating the prevalence of arthritis, and to examine the impact of arthritis on institutionalization and on the physical function of residents. Five homes were studied using a 3-phase approach. Directors of nursing in each home classified residents (n = 629) with respect to the presence of arthritis and senile dementia. The presence of osteoarthritis or rheumatoid arthritis and their impacts on a resident's initial placement were separately assessed by a physician through a chart review of a stratified subsample. The physician also rated a resident's likelihood of returning to community living. Finally, the functional impact of arthritis was assessed by a physical therapist. The nurses' estimate of the prevalence of arthritis in this population was 23.33%, while the physician estimate was 23.03%. These results are consistent with the 24.6% prevalence found in a 1977 national survey. Arthritis itself was a major cause of nursing home placement in 15% of all residents without dementia. Among those without dementia who also had arthritis, arthritis was a major cause of institutionalization in 31%. None of the residents without dementia showed substantial potential for reintegration into the community. Controlling for age, residents with arthritis had more pain, were more likely to require assistance in functional tasks, and were more likely to use a wheelchair daily than were their fellow residents. Nevertheless, our results suggest that arthritis, despite its impact on function, in and of itself is not a major cause of nursing home placement or ongoing institutionalization. PMID- 2597210 TI - Purification and characterization of Ki antigen and detection of anti-Ki antibody by enzyme-linked immunosorbent assay in patients with systemic lupus erythematosus. AB - Ki antigen from rabbit thymus extract was purified by ammonium sulfate precipitation, anti-Ki affinity chromatography, and high pressure liquid chromatography gel filtration. The purified Ki antigen gave a single polypeptide with an MW of 32,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it specifically reacted with anti-Ki antibody by immunoblotting. The isoelectric point of the Ki antigen was found by isoelectric focusing to be 4.3. An enzyme-linked immunosorbent assay using the purified Ki antigen was established, and the clinical significance of the anti-Ki antibody in systemic lupus erythematosus (SLE) was studied. Thirty of 140 patients with SLE (21.4%) had anti-Ki antibody by enzyme-linked immunosorbent assay, whereas 11 (7.9%) were positive by double immunodiffusion. Analysis of clinical and serologic data on patients with SLE suggested a higher prevalence of central nervous system involvement in patients with anti-Ki antibody. PMID- 2597212 TI - Elevated mean corpuscular volume as a predictor of hematologic toxicity due to methotrexate therapy. AB - Retrospective analysis of 23 rheumatoid arthritis patients receiving low-dose methotrexate (MTX) demonstrated an association between the mean corpuscular volume (MCV) and hematologic toxicity. All 6 patients who developed hematologic toxicity were folate deficient, and 4 of 6 had marked macrocytosis. Furthermore, the mean MCV of the patients who developed toxicity was significantly higher than that of the controls without toxicity (P less than 0.02). This difference in MCV was associated with an increased probability of developing toxicity with time (P less than 0.005). These results suggest that sustained elevation in the MCV may be a predictor of impending hematologic toxicity due to folate depletion. PMID- 2597211 TI - Differences in the fine specificity of anti-Ro (SS-A) in relation to the presence of other precipitating autoantibodies. AB - In sera from patients with systemic lupus erythematosus or Sjogren's syndrome, we determined the fraction of antibody that remained reactive with human Ro (SS-A) after absorption with bovine spleen extract, and the reactivity with the 60-kd and 54-kd red blood cell Ro (SS-A) bands by Western blot. Of the 3 groups of sera studied, those containing anti-Ro (SS-A) alone had the highest degree of reactivity with human Ro (SS-A) after absorption with bovine spleen extract, followed, in descending order, by sera containing anti-Ro (SS-A) and anti-La (SS B), and sera containing anti-Ro (SS-A) and anti-nuclear RNP. The groups of sera could be distinguished on this basis. Sera with anti-Ro (SS-A) and anti-nuclear RNP could also be distinguished from the other 2 types of sera by their uniform and preferential reactivity with the 60-kd red blood cell Ro (SS-A), by Western blot analysis. These findings indicate that there are both qualitative and quantitative differences, associated with the presence of other autoantibodies, in the fine specificity of anti-Ro (SS-A) sera. PMID- 2597213 TI - Prevalence of the use of unconventional remedies for arthritis in a metropolitan community. AB - Of 1,811 individuals sampled in a metropolitan community, 382 reported having a musculoskeletal complaint. Eighty-four percent of them had used an unconventional remedy within the previous 6 months. Most individuals used inexpensive, unharmful remedies such as exercise, prayer, and relaxation. This study indicates that people with musculoskeletal disorders often use unconventional remedies, but raises questions regarding the seriousness of this problem. PMID- 2597214 TI - Coccidioidomycosis of bone: a sequela of desert rheumatism. PMID- 2597215 TI - HLA-DR antigens and anticardiolipin antibodies in patients with systemic lupus erythematosus. PMID- 2597216 TI - Infectious complications of cyclophosphamide treatment for vasculitis. PMID- 2597217 TI - Effect of temperature and humidity on daily pain score in a patient with rheumatoid arthritis. PMID- 2597218 TI - Arthropathy of Behcet's disease: a case with "pencil-in-cup" deformities. PMID- 2597219 TI - Comment on the article by Thomson et al. PMID- 2597220 TI - Age-associated ultrastructural changes in the aortic intima of rats with diet induced hypercholesterolemia. AB - The ultrastructure of the aortic intima and serum lipid levels in Fischer 344 rats were examined at the ages of 12, 18 and 24 months after feeding the animals an atherogenic diet (2% cholesterol, 0.25% sodium cholate, 5% beef fat) for 6 months. Structural changes in the intima were noticeable only at the age of 24 months. In control rats, the endothelial cells were irregular in shape and each had a well-developed Golgi complex and a few lipid droplets. Simultaneously, reticular, basal lamina-like material and electron-dense granules of extracellular liposomes accumulated in the subendothelium. In fat-fed rats, these structural changes were more conspicuous in association with hypercholesterolemia, and numerous monocytes with lipid droplets were attached to the endothelium, occasionally invading into the subendothelium. Slight foam cell lesions were evident in the intima. The finding that older rats were more susceptible to the atherogenic diet suggests that atherogenesis in the rat is promoted by intrinsic age-associated changes in the aortic intima. PMID- 2597221 TI - Effects of exercise on hypocholesterolemia of stroke-prone spontaneously hypertensive rats. AB - The effects of exercise on hypocholesterolemia, one of the risk factors of cerebrovascular disorders, were examined. 47-51-day-old stroke-prone spontaneously hypertensive rats (stroke-prone SHRs) were assigned to 2 groups, sedentary or exercise, and raised for 8 weeks. The total serum cholesterol level of the exercised group was 17-18% higher (P less than 0.01) than the control group, and the level of cholesterol synthesis in the liver of the former group significantly higher than in the latter. On the other hand, the level of intestinal cholesterol synthesis in the exercised group was significantly lower. The activity of HMG-CoA reductase in the liver microsomes was significantly increased by exercise, but the activity of this enzyme in the small intestine was not affected. A significant correlation was observed between the rate of cholesterol synthesis in the liver and the amount of radiolabeled cholesterol released into the serum. From these results, we conclude that the enhancement of the synthesis and the release of cholesterol in the liver by exercise is a major cause of the exercise-induced increase in serum cholesterol of stroke-prone SHRs. PMID- 2597222 TI - Binding parameters and concentration modulate formation of complexes between LDL and arterial proteoglycans in serum. AB - The interactions of LDL with extracellular matrix proteoglycans apparently contribute to the accumulation of apo B-lipoproteins in atherogenesis. Serum LDL forms insoluble complexes with human arterial chondroitin sulfate proteoglycans (CSPG). While the amount of insolubilized LDL varies, serum from survivors of myocardial infarcts and ischaemic subjects shows higher values of CSPG insolubilized LDL than serum from controls. In this study, we explored the relationship between the formation of LDL-CSPG complexes in serum and some LDL properties, using binding isotherms and characterization of isolated LDL from 12 healthy controls and 12 young myocardial infarct survivors. The amount of LDL insolubilized in serum from solutions of CSPG was found to be a function of the product Bt (total binding) x the amount of serum LDL-cholesterol. Furthermore, the Bt values for the isolated LDL from controls and patients could be predicted with more than 70% certainty by using a multiple regression model which included the cholesterol/protein ratio, protein/triglyceride ratio, isoelectric point and the affinity coefficient of the lipoprotein for CSPG. The results indicate that LDL-CSPG measurements in serum are dependent upon both LDL concentration and structural properties which are related to its tendency to form complexes with arterial CSPG. PMID- 2597223 TI - Plasma sulfhydryl-containing amino acids in patients with cerebral infarction and in hypertensive subjects. AB - It has been postulated that an accumulation of a sulfhydryl-containing amino acid, homocysteine in plasma may induce arteriosclerosis. In order to explore a possible contribution of homocysteine to the development of cerebral infarction in middle-aged and elderly patients, plasma sulfhydryl-containing amino acid profiles of 45 patients with cerebral infarction (CI) were compared with those of 45 normotensive and 45 hypertensive controls, and 20 patients with cerebral bleeding (CB), of similar ages and sex. The concentrations of both free and total homocysteine in plasma were highest in patients with CI among the 4 groups, while plasma free and total cysteinylglycine levels were similar. Although both free and total cysteine levels were also higher in patients with CI than in normotensive controls, the total homocysteine/total cysteine ratio was highest in patients with CI among the four groups. The hypertensive controls had higher plasma free and total concentrations than normotensive controls, but the levels did not differ between the 21 normotensive and 24 hypertensive CI patients. Our results suggest that high levels of plasma homocysteine in conjunction with hypertension could be one of the risk factors for arteriosclerotic CI. PMID- 2597224 TI - Suppression of atherogenesis in cholesterol-fed rabbits treated with nilvadipine, a new vasoselective calcium entry blocker. AB - We examined the effects of nilvadipine, a new dihydropyridine calcium entry blocker, on atherogenesis in rabbits fed a 1% cholesterol diet. The drug was given subcutaneously to the animals in hypotensive doses of 1.0 or 3.2 mg/kg/day for 10 weeks, and was well tolerated. Plasma total cholesterol increased markedly in all the cholesterol-fed rabbits, and nilvadipine had no effect on this, or on HDL-cholesterol and triglyceride levels. However, the area of Sudan IV positive intimal lesions (one of the parameters of atherosclerosis) in the aorta decreased significantly in the nilvadipine treated animals, and in addition, cholesterol and calcium content in the thoracic aorta were reduced. The reference drugs, nifedipine and nicardipine given subcutaneously in doses of 10.0 mg/kg/day either had no effect or were weaker in antiatherogenic effect than nilvadipine. The findings suggest that nilvadipine has more potent antiatherogenic activity than nicardipine or nifedipine. PMID- 2597225 TI - Effects of dietary supplementation with marine lipid concentrate on the plasma lipoprotein composition of hypercholesterolemic patients. AB - Although the triglyceride-lowering actions of n-3 fatty acids of marine lipids are now well-recognized, their effects on plasma lipoproteins have not been studied systematically in patients with hypercholesterolemia. To address this question, we supplemented the Phase 1 American Heart Association diets of 14 hypercholesterolemic ambulatory outpatients with a commercially available preparation of marine lipid concentrate (SuperEPA) containing 7.5 g n-3 fatty acids per day and studied their plasma lipids and lipoproteins before and after 30 days of treatment. Both plasma triglyceride and cholesterol levels fell uniformly in all patients while the mean VLDL- and LDL-cholesterol decreased by 58% (P less than 0.005) and 13% (P less than 0.025) respectively. The decrease in whole plasma cholesterol was significantly correlated with the fall in LDL cholesterol (r = 0.85, P less than 0.01), and not VLDL-cholesterol (r = 0.39, NS). Among the other potentially beneficial actions observed was an increase in HDL2 in all patients (mean increment 41%, P less than 0.005), and an increase in the HDL2/HDL3 ratio (+46%, P less than 0.001) and decreases in the LDL/HDL ratio (-14%, P less than 0.005) and in the unesterified cholesterol/lecithin ratio ( 17%; P less than 0.001) in plasma. The increase in the unesterified cholesterol/esterified cholesterol ratio in VLDL and HDL3 suggested that marine lipid therapy resulted in a reduction in the size of lipoprotein particles in these fractions. Since these changes may reduce cardiovascular risk, these findings suggest that marine lipids may prove useful in the treatment of certain patients with hypercholesterolemia. PMID- 2597226 TI - Effect of yogurt intake on plasma lipid and lipoprotein levels in normolipidemic males. AB - To determine the effect of yogurt intake on plasma lipid and lipoprotein levels, studies were carried out in 18 normolipidemic males during 3 dietary phases. Phase 1 was a low-fat, low-cholesterol baseline diet consumed for 3 weeks. The baseline diet was supplemented with low-fat yogurt (16 oz/day) for 4 weeks during phase 2, and during phase 3 the supplement consisted of a non-fermented dairy product (16 oz low-fat milk plus 10% milk solids). Average body weights and dietary intakes of fat, cholesterol and polyunsaturate/saturate fat ratios were not significantly different for the 3 dietary phases. Plasma total, LDL- and HDL cholesterol were unaffected by either the yogurt of low-fat milk concentrate. The results indicate that yogurt, as an example of a fermented dairy product, has no effect on plasma cholesterol levels of normolipidemic males. PMID- 2597227 TI - Cytochemical localization of beta-lipoproteins and their components in successive stages of hyperlipidemic atherogenesis of rabbit aorta. AB - We have investigated cytochemically the correlative distribution of lipoprotein (LP) components in successive lesional stages of plaque formation in hyperlipoproteinemic atherogenesis in the rabbit. Apoprotein B (apo B) was detected by an immunoperoxidase procedure, unesterified cholesterol (UC) by filipin and tomatine and phospholipid lamellae of the extracellular liposomes (EL) as they appear in standard EM. The changes were evaluated in relation to the state of endothelial cells and their transport pathways, and the reaction of the cellular and extracellular components of the intima. Each lesional stage has a relatively characteristic pattern distribution of the LP components. In fatty streaks with no endothelial denudation, apo B reaction product occurs mostly in non-particulate form associated with UC-rich EL; this suggests that transcytosed LP upon partial degradation and interaction with the extracellular components, reassemble as polymorphic EL-UC-apo B complexes. Serofibrinous insudates, although commonly devoid of EL and apo B, may contain UC presumably transported by a carrier other than LP. In advanced fibrolipidic lesions with open endothelial junctions and deendothelialized areas, a bulky intramural insudation of plasma results in the presence of large amounts of apparently little modified LP. This may represent what several investigators have isolated as 'aortic LP', which may be insudated rather than transported plasma LP. PMID- 2597228 TI - Dyslipoproteinemia in murine systemic lupus erythematosus. AB - Dyslipoproteinemia, a feature of systemic lupus erythematosus may contribute to premature atherosclerosis. In order to develop an experimental model for this dyslipoproteinemia we measured plasma concentrations of lipoproteins in juvenile NZB/W (lupus) and NZB/B (control) mice. Additionally to evaluate the effects of a diet rich in n - 3 fatty acids we measured lipoprotein concentrations in mice on normal or menhaden oil-enriched diets. The lupus mice had elevated triglycerides compared to the controls, similar to that seen in human SLE patients (161 +/- 31 vs 113 +/- 13 mg/dl, P less than 0.003). In contrast, the menhaden oil diet fed NZB/W mice had triglycerides similar to the NZB/B control fed group. In the NZB/W murine SLE model, dyslipoproteinemia is an early sign of disease as has been shown in man, therefore this model will be useful in elucidating the mechanism of dyslipoproteinemia in SLE. PMID- 2597229 TI - Stimulation of rat peritoneal mast cells enhances uptake of low density lipoproteins by rat peritoneal macrophages in vivo. AB - The effect of mast cell stimulation on the uptake of low density lipoproteins (LDL) by macrophages was tested in vivo in the peritoneal cavity of the rat, a site known to contain both macrophages and mast cells. The concentration of LDL in the peritoneal cavity was raised by injecting [14C]sucrose-labeled LDL ([14C]sucrose-LDL). In the treated rats, in the absence of mast cell stimulation, the uptake of LDL by the peritoneal macrophages was low. But when the peritoneal mast cells were concomitantly stimulated by intraperitoneal administration of compound 48/80, an agent known to induce mast cell degranulation, the rate of uptake of labeled LDL by macrophages rose by 7-24-fold. The reason for this rise was that exocytosed mast cell granules bound LDL and carried it into macrophages when phagocytosed. Thus, cyclohexanedione treatment of LDL, or injection of avidin along with LDL, 2 measures known to inhibit binding of LDL to mast cell granules, totally prevented the mast cell-dependent uptake of LDL. Furthermore transmission electron microscopic studies with gold-labeled LDL disclosed phagocytosis of LDL-bearing granules by the peritoneal macrophages. This is the first demonstration of a natural proteoglycan being able to enhance the rate of LDL uptake by macrophages in vivo. These observations on the relation between stimulation of mast cells and uptake of LDL by macrophages in vivo may have relevance in other sites where mast cells and macrophages coexist, such as the arterial intima. PMID- 2597230 TI - Kinetics of HDL-apo A-I in the WHHL rabbit, an animal model of familial hypercholesterolemia. AB - Plasma high density lipoproteins (HDL) and their major protein, apolipoprotein (apo) A-I, are deficient in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits. As the pathophysiology of subnormal HDL-apo A-I is unclear, we examined kinetic parameters of HDL-apo A-I in WHHL rabbits and normolipidemic Japanese White (control) rabbits. The total plasma mass of HDL-apo A-I was significantly smaller (P less than 0.01) in WHHL rabbits than in controls (less than one third). Mean fractional catabolic rates (FCR) computed from the specific radioactivity decay curves of HDL-apo A-I were significantly greater (P less than 0.01) in WHHL rabbits than in controls (0.874 +/- 0.052 vs. 0.502 +/- 0.060/day, respectively). Mean synthetic rates of HDL-apo A-I were significantly lower (P less than 0.01) in WHHL rabbits than in controls (8.67 +/- 0.59 vs. 18.14 +/- 3.75 mg/kg body weight/day, respectively). We conclude that the deficiency of plasma HDL-apo A-I in the WHHL rabbits resulted from an increase in FCR and a decrease in apo A-I synthesis. PMID- 2597231 TI - Procoagulant activity expression by macrophages from atheromatous vascular plaques. AB - Embolization of thrombi from ulcerated plaques is an important cause of morbidity from atherosclerotic carotid artery disease. Factors controlling thrombus formation on these lesions are not well understood. Macrophages were isolated from atherosclerotic plaques to assess their potential to promote local fibrin deposition. Plaques were collected from 11 patients undergoing carotid endarterectomy and 9 patients undergoing reconstructive procedures for atherosclerotic disease of their distal aorta or femoral arteries. Blood was also collected concurrently to isolate monocytes. Procoagulant activity (PCA) of carotid macrophages (8.6 +/- 4.1 mU/10(6) cells) was significantly higher than that of macrophages from non-carotid lesions (0.35 +/- 0.20 mU/10(6) cells; P less than 0.05) or blood monocytes from either group of patients. The PCA of carotid plaque macrophages from patients with recent emboli was 16.1 +/- 8.4 mU/10(6) cells (n = 5) compared to 2.4 +/- 0.8 mU/10(6) cells (n = 6) for plaque macrophages from assymptomatic carotid endarterectomy patients. Carotid macrophage PCA was factor V and factor VII dependent. Its functional activity was inhibited by an anti-tissue factor antibody, and immunohistochemical studies on tissue sections from carotid plaques showed tissue factor in areas where macrophages were abundant. These studies demonstrate that macrophages within carotid artery plaques have augmented procoagulant activity compared with blood monocytes and macrophages from other atherosclerotic lesions and indicate that carotid plaque macrophages are activated. Augmented macrophage PCA may contribute to thrombus formation on ulcerated plaques. PMID- 2597232 TI - Cigarette smoking renders LDL susceptible to peroxidative modification and enhanced metabolism by macrophages. AB - The effect of cigarette smoking on peroxidation of plasma low density lipoprotein (LDL) was studied in 16 smokers aged 23-56 years; 12 nonsmokers of similar age served as controls. The smokers were asked to refrain from smoking 24-40 h prior to testing. Peroxidation was assessed by determination of thiobarbituric acid reactive substances (TBARS) in fresh plasma and LDL and by an increase in 125I LDL metabolism by peritoneal macrophages. There was no difference in TBARS in freshly prepared plasma or LDL of smokers and nonsmokers. However, LDL of smokers, conditioned by incubation with bovine aortic smooth muscle cells (SMC), had 2-fold or higher TBARS values when compared to SMC conditioned LDL of nonsmokers. 2-4-fold higher TBARS values were seen also in SMC conditioned LDL when the comparison was made between LDL isolated from plasma before smoking of 6 7 cigarettes (time 0), and LDL of the same individual isolated from plasma 90 min thereafter. The metabolism of SMC conditioned 125I-LDL by peritoneal macrophages was examined; LDL isolated from plasma of smokers at time 0 was metabolized twice as avidly as LDL of nonsmokers and a further increase was seen with LDL isolated 90 min after acute smoking. The present results indicate that cigarette smoking renders plasma LDL more susceptible to subsequent peroxidative modification by cellular elements. PMID- 2597233 TI - Inhibition of cholesterol biosynthesis in freshly isolated blood mononuclear cells from normolipidemic subjects and hypercholesterolemic patients treated with bezafibrate. AB - Bezafibrate was given for 15 days at a dose of 200 mg t.i.d. to 4 normolipidemic subjects, to 5 patients with putative heterozygous familial hypercholesterolemia, and to 6 patients with primary hypercholesterolemia of the non-familial type. At the end of the treatment, the rate of incorporation of labelled acetate into non saponifiable lipids in freshly isolated blood mononuclear cells decreased in all subjects. On the average, acetate incorporation decreased by 31% in cells from normolipidemic subjects, 41% in cells from familial, and 45% in cells from non familial hypercholesterolemia patients. Results of the present study suggest that the lowering effect of bezafibrate on serum cholesterol is mainly due to the inhibition of cholesterol synthesis through the suppression of HMG-CoA reductase as was demonstrated in rat hepatocytes and in cultured human blood mononuclear cells. PMID- 2597234 TI - Plasma apolipoproteins in patients with multi-infarct dementia. AB - We examined 27 elderly patients with multi-infarct dementia developed on the basis of cerebral arteriosclerosis. The levels of plasma cholesterol and triglyceride in the patients were 177 +/- 48 and 91 +/- 27 mg/dl (mean +/- SD), respectively. Despite normal plasma lipid levels, the patients had significantly higher plasma apo B (102 +/- 30 vs. 82 +/- 21 mg/dl for controls, P less than 0.01) and lower plasma apo A-I levels (104 +/- 25 vs. 130 +/- 22 mg/dl for controls, P less than 0.01) than the controls. Isoelectric focusing of apo E showed a 2-fold higher relative frequency for the epsilon 4 allele in patients than in Japanese controls (20.8 vs. 8.6-11.7% of total, P less than 0.05). The patients with phenotypes of E4/4 (n = 1) and E4/3 (n = 8) had higher plasma cholesterol levels than those with E3/3 (n = 15) (196 +/- 45 vs. 169 +/- 43 mg/dl). The results indicate that the patients had abnormalities in plasma lipoprotein metabolism and this may contribute to the development of cerebral arteriosclerosis. PMID- 2597235 TI - Modification of low density lipoproteins from hypertriglyceridemic patients by macrophages in vitro and the effect of bezafibrate treatment. AB - After 30 days of bezafibrate administration to 5 patients with hypertriglyceridaemia and hyperapobetalipoproteinaemia a rise was found in the concentrations of cholesterol and vitamin E in the LDL fraction. In consequence the susceptibility of the LDL fraction to oxidation by macrophages was reduced. The uptake of modified LDL by these cells was decreased in relation to the uptake before treatment. PMID- 2597236 TI - Lack of effect of probucol on serum lipoprotein(a) levels. PMID- 2597237 TI - Leads from the MMWR. Leading major congenital malformations among minority groups in the United States, 1981-1986. PMID- 2597238 TI - An analysis of birth weight by gestational age in Canada. AB - Birth-weight-gestational-age standards help to identify infants in need of special care and to determine causes and means for preventing retardation of intrauterine growth. Previously published standards either were based on small samples, data several decades old or characteristics of subpopulations in the United States or they were not specific for type of birth and sex. We compared the data for live births in 1972 with those in 1986 to develop current Canadian standards for type of birth (singleton or twin) and sex. We found that the 10th, 50th and 90th percentile figures for weight were slightly higher in 1986 than in 1972 for term deliveries (at 37 weeks' gestation or later), but the figures were virtually unchanged for preterm deliveries. The availability of reliable population-based standards should enhance the clinician's ability to identify true cases of retardation or acceleration of intrauterine growth. PMID- 2597239 TI - The constitutional right to health care. Denial in the court. PMID- 2597240 TI - Heart rate, activity, duration, and affect in added-purpose versus single-purpose jumping activities. AB - This research replicates and extends an occupational therapy research project reported by Kircher in 1984. Thirty women aged 18 to 31 years jumped with a rope on one day and jumped in place on another day in a counterbalanced design. Each subject stopped jumping when she reached what she perceived as the very hard level on the Borg Scale of Perceived Exertion (Borg, 1970). Differences from Kircher's design included an imposed target zone formula for safe maximum exertion, use of a portable, more easily read heart rate monitor (Exersentry, Model 3), use of the Osgood Semantic Differential to measure affective meanings, and asking the subjects to identify the type of jumping they preferred. Data analysis supported Kircher's finding that at the given rate of perceived exertion, heart rate increase after jumping rope was significantly higher (p = .01) than after jumping without a rope. The difference in duration of jumping approached significance (p = .06), but in the direction opposite to what Kircher found. There were no significant differences in affective meanings or preference. Results are discussed in terms of the need for a growing body of occupational therapy literature in regard to the purposefulness of activities. PMID- 2597241 TI - Blood transfusions and recurrence in head and neck cancer. AB - Recent reports in the general surgery literature have shown decreased survival with blood transfusions in abdominal cancer surgery. We reviewed our experience with 100 consecutive patients, all of whom had 5-year follow-up, to see if this held true for head and neck cancer. The detailed report covers site and stage. In summary, however, the recurrence rate for all cancers of the larynx was 14% for those who did not receive blood and 65% for those who did. For cancer of the oral cavity, pharynx, and nose or sinus, the recurrence rate was 31% without transfusions and 71% with transfusions. It would appear that the use of blood transfusions somehow adversely affects the patient's survival. Further study needs to be done to elucidate the mechanism. PMID- 2597242 TI - Predictive values. PMID- 2597243 TI - Autosomal recessive pericentral pigmentary retinopathy. PMID- 2597244 TI - Problems in the taxonomy of alcoholism. PMID- 2597245 TI - Pharmacy fax. PMID- 2597246 TI - Static and dynamic components of the chiropractic subluxation complex: a literature review. PMID- 2597247 TI - The effects of cigarette smoking on glycosylated hemoglobin in nondiabetic individuals. AB - Cigarette smoking has been causally linked to atherosclerotic heart disease. The mechanism by which cigarette smoking causes heart disease has not, however, been determined. Nicotine has been shown to lead to increases in plasma epinephrine and norepinephrine following smoking. Catecholamines have been shown to lead to increases in blood glucose. This paper demonstrates that cigarette smoking is associated with increases in average blood glucose as measured by glycosylated hemoglobin levels in smokers compared with nonsmokers. Fifteen nondiabetic smokers had an average glycosylated hemoglobin of 6.82% (SD = 1.06%), which is higher than the 5.63% (SD = .49%, t = 3.98, P less than .001) found for 23 nonsmokers. The average glycosylated hemoglobin level of the smokers is in the range found for patients with well-controlled diabetes. These data suggest that elevated blood glucose may contribute to atherogenesis in cigarette smokers. PMID- 2597248 TI - Health-care interpreters and cancer. PMID- 2597249 TI - Adenotonsillectomy: a safe outpatient procedure. PMID- 2597250 TI - Appearance of a second malignant clone associated with extramedullary spread in a case of 'smouldering' multiple myeloma. PMID- 2597251 TI - Does terbutaline cause uterine atony and increase intraoperative blood loss? PMID- 2597252 TI - Treatment of renal failure in neonates. PMID- 2597253 TI - Periodic health examination, 1989 update: 1. Introduction [corrected]. PMID- 2597254 TI - Hepatitis B immunisation of dental students in 14 UK dental schools. PMID- 2597255 TI - Prazosin-induced priapism. PMID- 2597256 TI - A cross Canada survey of neurologists on controversial issues in epilepsy management. PMID- 2597257 TI - Hemoptysis due to LV pseudoaneurysm. PMID- 2597258 TI - Diagnosing thymic neoplasia. PMID- 2597259 TI - Sialic acid: ambiguous marker of pepsin-degraded mucus. PMID- 2597260 TI - Comparison of forceful dilatation and oesophagomyotomy in achalasia. PMID- 2597261 TI - Alcoholic hepatotoxicity. PMID- 2597262 TI - Application of the AgNOR method to cell imprints. PMID- 2597263 TI - Metabolic stroke in methylmalonic acidemia. PMID- 2597264 TI - Raynaud's phenomenon and nifedipine. PMID- 2597265 TI - Arterial response to in vivo excimer laser irradiation. PMID- 2597266 TI - Hypertension, race, and renal insufficiency. PMID- 2597267 TI - Treatment of autoimmune thrombocytopenic purpura. PMID- 2597268 TI - Immunologic effects of vitamin D. PMID- 2597269 TI - Neuromuscular thermography. PMID- 2597270 TI - BCAA-enriched solution and hepatic encephalopathy. PMID- 2597271 TI - Withdraw of product licences. PMID- 2597272 TI - High-tech beds and mattress overlays. A decision guide. PMID- 2597273 TI - Epidural fentanyl and lithotripsy. PMID- 2597274 TI - Ciprofloxacin and warfarin. PMID- 2597275 TI - Face masks as protection from laser plume. PMID- 2597276 TI - Use of fiberoptic vs conventional pulmonary artery catheters. PMID- 2597277 TI - 1,2-Diacylglycerol accumulation in human neutrophils does not correlate with respiratory burst activation. AB - Measurements of the level of 1,2-diacylglycerol (1,2-DG) during activation of the respiratory burst of human neutrophils by formyl-methionyl-leucyl-phenylalanine (fMLP) in the presence of platelet-activating factor (PAF) or by opsonized particles show that a correlation between accumulation of 1,2-DG and O2 consumption does not exist. Inhibition of protein kinase C activity with staurosporine before addition of opsonized particles demonstrates that the first phase of the respiratory burst is not inhibited, whereas the second phase, which is accompanied by a rise in the content of 1,2-DG, is strongly inhibited. This study indicates that accumulation of 1,2-DG cannot be the sole signal for the initiation of the respiratory burst in human neutrophils. PMID- 2597278 TI - Ramoplanin (A-16686), a new glycolipodepsipeptide antibiotic. III. Structure elucidation. AB - By combination of chemical, 1H and 13C NMR, and mass spectrometric studies, the structures of the three components of the antibiotic ramoplanin (A-16686), produced by Actinoplanes sp. ATCC 33076, have been elucidated. All the components have structures formed by a common depsipeptide skeleton carrying a dimannosyl group and are differentiated by the presence of various acylamide moieties, derived from C8, C9 and C10 fatty acids. PMID- 2597279 TI - Pharmacodynamics and causes of dose-dependent pharmacokinetics of flavone-8 acetic acid (LM-975; NSC-347512) in mice. AB - Flavone acetic acid (FAA) is a novel antitumor agent with broad solid-tumor activity. However, this drug has shown a steep dose-response curve in preclinical trials, with a narrow sublethal window of efficacy. To investigate this threshold behavior, we studied various aspects of FAA pharmacology in mice after i.v. administration. Mice bearing advanced-stage s.c. colon 38 adenocarcinoma were treated at four dose levels (39, 65, 108 and 180 mg/kg), and only the highest dose produced significant antitumor activity, showing a steep dose-response curve. Using an HPLC assay, FAA pharmacokinetics in both plasma and tumors were found to be dose-dependent. As the dose increased, there was a decrease in both total body clearance and volume of distribution at steady state. The increase in tumor area under the curve (AUC) was more pronounced than the corresponding increase in plasma AUC, showing a better tumor exposure to FAA at high doses. The distribution of FAA in normal tissues showed a short-term retention in the liver and kidneys; low concentrations were observed in the heart, spleen, and brain, with some retention in the latter. The highest FAA concentrations were found in the gastrointestinal (GI) tract, mainly in the duodenum, suggesting an important biliary excretion of the drug. Various possible causes of FAA nonlinear pharmacokinetics were investigated. Serum protein binding was high (79%) and remained constant up to 100 micrograms/ml, but decreased thereafter at higher FAA concentrations, e.g., 76% at 500 micrograms/ml and 64% at 1,000 micrograms/ml. Urinary and biliary clearances were dose-dependent and decreased 5- and 9-fold, from the 39- to the 180-mg/kg dose levels, respectively. A direct assessment of FAA enterohepatic circulation using intercannulated mice showed that 27% of the plasma AUC was accounted for by enterohepatic circulation. FAA acyl glucuronide was identified as the major metabolite in mice and was found to contribute to the nonlinear pharmacokinetics due to its facile hydrolysis under physiological conditions, regenerating FAA. In conclusion, the steep FAA dose-response curve was found to be caused by dose-dependent pharmacokinetics in mice. The nonlinear pharmacokinetics of this drug was attributed to a dose-dependent decrease in both urinary and biliary clearances, concentration-dependent serum protein binding, enterohepatic circulation, and the instability of FAA acyl glucuronide under physiological conditions forming a futile cycle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2597280 TI - Pyrrolizidine alkaloids from Cynoglossum creticum. Synthesis of the pyrrolizidine alkaloids echinatine, rinderine, and analogues. AB - Reinvestigation of Cynoglossum creticum led to the isolation of the previously reported echinatine [1] and heliosupine [2] as well as rinderine [3], 7 angelylheliotridine [4] and a new alkaloid, cynoglossamine [5]. The structures have been determined by spectral means (ir, ms, 1H-13C HETCOR nmr), comparison with literature data and authentic samples, and/or syntheses. In addition, 1 and all three of its isomers 3, 6, and 7 and other semisynthetic analogues (8-13) were prepared and characterized. PMID- 2597281 TI - Achatin-I, an endogenous neuroexcitatory tetrapeptide from Achatina fulica Ferussac containing a D-amino acid residue. AB - A tetrapeptide named achatin-I was purified from the suboesophageal and cerebral ganglia of the African giant snail Achatina fulica Ferussac, and evoked a potent neuroexcitatory effect. The amino acid sequence of achatin-I is Gly-D-Phe-Ala Asp. Achatin-I induced a voltage-dependent inward current, due to Na+, on the identifiable giant neuron, periodically oscillating neuron (PON), of the same snail. All possible isomers of achatin-I were synthesized using the solid-phase method. The sensitivity of the neuron to achatin-I and its isomers was strictly stereospecific; among the various isomers, only achatin-I showed marked effects (ED50 = 2.29 x 10(-6)M), while Gly-D-Phe-D-Ala-Asp, the synthetic D-Ala-isomer, was less than 10(-3) active. PMID- 2597282 TI - Fluorogenic reagent for thiols: 4-(N,N-dimethylaminosulphonyl)-7-fluoro-2,1,3 benzoxadiazole. AB - 4-(N,N-Dimethylaminosulphonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F) was synthesised for use as a more reactive, thiol-specific fluorogenic reagent than 4 (aminosulphonyl)-7-fluoro-2,1,3-benzoxadiazole (ABD-F). The former had negligible fluorescence whereas its thiol derivatives fluoresced intensely at about 510 nm (excitation occurred at about 380 nm). The DBD-F reacted quantitatively with thiols after 10 min at 50 degrees C and pH 8.0 and the reaction rates were several times higher than those with ABD-F; it is suggested that the electron withdrawing effect of the dimethylsulphonamide group (SO2NMe2) is larger than that of the sulphonamide group (SO2NH2). No reaction occurred with alanine, proline, cystine or cysteic acid under the same conditions. The fluorescence intensities of the derivatives were found to be higher in neutral and acidic media than in alkaline solutions. The thiol derivatives of DBD-F were separated by high-performance liquid chromatography and detected fluorimetrically, the detection limits being 0.92, 0.16, 0.13, 0.16 and 0.32 pmol for cysteine, glutathione, homocysteine, N-acetylcysteine and alpha-mercaptopropionylglycine, respectively. The method was applied to the determination of thiols in rat tissues. PMID- 2597283 TI - Reduction of cytotoxic effector cell activity in colon 38 tumours following treatment with flavone acetic acid. AB - Host cells have been implicated as being involved in the antitumour effects of flavone acetic acid (FAA), an agent with selectivity towards solid tumours which is currently undergoing clinical trial. To determine whether tumour-associated host cells are affected by FAA treatment, tumour-infiltrating leukocytes (TIL) were isolated from subcutaneous Colon 38 tumours, which are known to be sensitive to FAA. 1-2 x 10(5) TIL were isolated per gram of tumour, comprising mainly small lymphocytes and macrophages. Spontaneous activity against YAC-1 and P815 tumour targets was tested in a 4 h 51Cr-release assay for lymphoid cytotoxic effector cells. High levels of activity were exhibited by TIL against both P815, which is resistant to natural killer (NK) cells, and to NK-sensitive YAC-1 cells. In contrast, splenic cell populations contained only NK cell activity. Within 1 h of intraperitoneal administration of FAA (330 mg/kg) the cytotoxic effector cell activity of the TIL population was dramatically depressed, remaining low during the time in which extensive tumour necrosis became evident. In contrast, splenic NK activity was unchanged at 1 h and elevated at 4 h. The decrease in lymphoid killer activity of the TIL population following treatment argues against the primary involvement of these effector cells in mediating the antitumour action of FAA. PMID- 2597285 TI - The occupational health nurse as an employee assistance program provider. AB - EAPs increased from approximately five in 1945 to more than 5,000 in 1980. EAPs derive their mandate to assist employees in avoiding the negative impact of personal problems on job performance. Occupational health nurses must be familiar with the treatment resources in the community and the company's benefit programs. An occupational health nurse with good diagnostic and interviewing skills may find it possible to intervene with troubled employees before their job performance is impaired. PMID- 2597284 TI - Effects of platelet-activating factor on ion transport in isolated rat jejunum. AB - In isolated normal rat jejunum, platelet-activating factor (PAF) induced a dose dependent increase in short-circuit current (Isc) that was reduced in chloride free buffer and inhibited by the Cl- channel blocker, diphenylamine-2 carboxylate. An immediate rise in Isc (early phase) occurred that fell to a new elevated base line by 15 min (late phase). These responses to PAF occurred only when experiments were conducted at or before approximately 9 A.M. Early phase responses were blocked by the specific PAF antagonists, BN52021 and WEB2086, and were inhibited by the neurotoxin, tetrodotoxin. Early and late phases were also reduced by cyclooxygenase inhibitors and by doxantrazole, a mast cell stabilizing drug. However, histamine and serotonin antagonists were ineffective. We conclude that PAF causes changes in ion transport that include Cl- secretion and acts on the epithelium possibly via an intermediate cell and enteric nerves. In addition, known PAF receptors are involved in one component of the response that appears to follow a circadian rhythm. PMID- 2597286 TI - Employee assistance program evaluation. Employee perceptions, awareness, and utilization. AB - Periodic evaluation is necessary to maintain a quality employee assistance program. This survey was undertaken to determine employee awareness of the existing EAP and their satisfaction with the program. Likewise, the survey allowed for employee input on areas of the program they had concerns with that may have caused hesitancy in further use of the program. The survey not only documents to management that the program is of value to employees and identifies areas where changes may be focused in the future to meet employee needs, but actually serves as a communication tool in itself as a reminder of the availability of the Employee Assistance Program. PMID- 2597287 TI - The need for a more holistic health care system. AB - As a result of the evolution of health problems in the United States, the current health care system must change its focus from the traditional biomedical model to a holistic health oriented model. The holistic health oriented system is based on the enhancement and maintenance of health, not on the cure of disease. Given positive research findings concerning the health and cost benefits of worksite health promotion programs, it appears that industry, along with third party payers, nurses, and other health care professionals, could alter the emphasis and direction of health care. The worksite provides an ideal setting for the development of holistic programs. The occupational health nurse, whose role involves health promotion, health protection, environmental screening, and illness intervention, is in the best position to work with management in developing health promotion programs. PMID- 2597288 TI - Enhancing the image of the occupational health nurse. PMID- 2597289 TI - OSHA proposed rule. Occupational exposure to bloodborne pathogens [54 FR 23042, May 30, 1989]. PMID- 2597290 TI - Undergraduate and graduate education in prosthodontics in continental Europe. AB - Many factors, such as reduction in caries and periodontitis prevalence, decrease in the number of edentulous patients, and more frequent demand for implants, will have an important influence on prosthodontic treatment in the future. To provide more data on the reaction of prosthodontic departments to these changes and the implication in the teaching and training of dental students, a survey with 25 questions was sent to 40 universities in five European countries. The questions referred to teaching and training time in the three branches of prosthodontics; integration of periodontics, occlusion, and orthodontics; implant dentistry; and graduate training and postgraduate programs. The survey revealed that teaching and training in prosthodontics is still very conservative, not biologically oriented, and neglecting the future impact of changes in prevalence of caries and periodontal disease. PMID- 2597291 TI - Prosthodontic education in Japan. AB - The need for prosthodontic instruction in Japan is increasing as the mean age of its population rises. The Japanese government formulated a policy in 1967 to ensure a sufficient number of dentists to deal with the challenge; with this new course of action has come an increased standard of dental care. Even though prosthodontic education occupies 20% of the 4-year predoctoral program in Japan, the author feels that predoctoral prosthodontic education must be improved to meet the needs of its people. PMID- 2597292 TI - Functional disturbances in complete denture patients. AB - One hundred complete denture wearers were evaluated for mandibular dysfunction by collating information gathered with a questionnaire and physical examination. The most frequent symptoms centered on poorly fitting and functioning dentures, headaches, and pain in the neck and temporomandibular joints. Ninety-four percent of the patients demonstrated clinical signs of mandibular dysfunction. Two-thirds of the patients had decreased facial height, marked dental attrition, and significant occlusal discrepancies in the dentures. Periodic recall is suggested for the evaluation of mandibular dysfunction in all denture patients. PMID- 2597293 TI - Some effects of varying denture base resin polymer/monomer ratios. AB - Variations in the polymer/monomer mixing ratios from 1.5:1 to 4.5:1 vol/vol have been evaluated to determine the effect on dimensional accuracy and impact resistance of a PMMA homopolymer. Two polymerisation cycles were used. It was shown that a wide variation in mixing ratios (1.5:1 to 4:1) had no effect on dimensional accuracy or impact resistance and that a polymerisation cycle that includes a final boiling period is preferred. It was further found that notched impact resistance was almost an order of magnitude below unnotched impact resistance, emphasising the weakening effect of sharp contours on the impact resistance of denture resins. PMID- 2597294 TI - The application of Moire topography to removable prosthodontics. AB - The study was designed to assess the dental research potential of moire topography--the use of geometrically regular light patterns for measuring three dimensional objects. One hundred thirty-nine maxillary edentulous casts and 20 mounted cast pairs were evaluated. Results demonstrated that the moire topography techniques can be used to quantitatively evaluate edentulous arch forms, compare edentulous ridge forms and surfaces, determine the amount of overlap of mounted maxillary and mandibular casts, and confirm prime areas for positioning posterior teeth. PMID- 2597295 TI - Effect of canine guidance on the working condylar path. AB - The purposes of the study were to compare the relationship of anterior guidance with condylar movement and to analyze the three-dimensional relationship of canine guidance and the working condylar path. The mandibular movements of ten subjects with normal dentitions and no observable temporomandibular joint abnormalities were recorded using an electronic mandibular measuring system capable of measuring six degrees of freedom. Measurements were made employing both canine and clutch guidance. The data were collated and evaluated making use of mathematical modeling techniques. It was shown that the movements of the working condyle were affected by anterior guidance. When canine guidance is not consistent with the working condylar path, there is a sagittal displacement of the working path created to compensate for the lack in harmony. PMID- 2597296 TI - Radiographic stress measurement of two metal ceramic gold alloys. AB - A study was conducted to determine if radiographic stress measurement during the fabrication of a metal ceramic crown on gold alloys was possible. Stress in the longitudinal direction was radiographically calculated in the cast specimens (6 mm X 18 mm) after casting, sandpaper polishing, oxidation, and each firing process. Samples were also examined by x-ray diffraction. The results confirmed that radiographic stress measurement is possible for alloys with 70% to 80% gold content. PMID- 2597297 TI - A pilot study of polymerization inhibition of poly (vinyl siloxane) materials by latex gloves. AB - Intraoral inhibition of two poly (vinyl siloxane) low-viscosity impression materials was experienced when making an impression of prepared anterior teeth. It was hypothesized that the noted inhibition was a result of contamination with latex gloves. A screening test demonstrated inhibition of polymerization of three different materials when placed in contact with a surface that had been touched with one brand of latex gloves. This inhibition also occurred even if the gloves were washed prior to contact or if the surface was washed after contact with the gloves. Further studies are underway to determine which brands of gloves are safe to use. PMID- 2597298 TI - Ceramic shade determination: current technique for a direct approach. AB - A method for selecting the optimal shade of a ceramic restoration is presented. The shade is determined using a direct approach, facilitating communication with the laboratory. The dentist generates a custom shade tab using unfired dental porcelain powder mixed with an organic binder which has a refractive index that is adjusted to the fired material. Hue, chroma, value, and translucency are verified by direct comparison with the tooth to be replicated. Necessary adjustments are ascertained prior to fabricating the restoration, minimizing postfabrication alterations. PMID- 2597299 TI - Occlusal contacts in mandibular retrusion. AB - An investigation into mandibular retrusion and the relationship between the maximum intercuspal position and the most retruded mandibular position was conducted on 15 dental students and nurses who had reasonably intact dentitions and a well-defined intercuspation. A photographic method was used to measure the retrusion that occurred at the occlusal surfaces of the posterior teeth. An average of approximately 0.2 mm retrusion was found, and the explanation of the relatively large "apparent" retrusion led to a discussion of the mandibular axes of opening. PMID- 2597300 TI - Clinical classification of maximal opening and closing movements. AB - Opening and closing mandibular border movements of 250 subjects, 130 with clinical signs of TMJ pathosis and 120 normal subjects, were evaluated by measuring incisal interocclusal distance and recording mandibular movement on a tracking device. Both maximal opening and closing pathways were divided into initial and secondary phases, and were further classified into seven patterns on the basis of anomalous mandibular movements. Subjects with TMJ sounds tended to show mandibular deviations in the second phase, while those with tenderness to muscle palpation tended to show deviations in both phases. Subjects with bruxism demonstrated twice as many deviations in the second phase. PMID- 2597301 TI - Effects of nicotine chewing gum on complete dentures and their soft-tissue bearing areas. AB - One hundred six edentulous subjects were given nicotine-containing chewing gum to evaluate the ability to chew the gum, to observe the adherence of the gum to denture-base materials, and to evaluate the effect of gum chewing on denture bearing tissues. Prior to the 13-week study, the denture-bearing ridges and the tissue and polished surfaces of the denture were evaluated clinically and photographed. Questionnaires were used to elicit personal habits of the subjects. Of the 59 subjects completing the study, most could manipulate and chew the gum effectively, three-fourths reported that gum adherence was not a problem, and no adverse reaction to oral tissues was observed. PMID- 2597302 TI - A comparison of resins for fabricating provisional fixed restorations. AB - Four acrylic resins and two composite resins for fabricating provisional fixed prosthodontic restorations were studied to determine temperature change during polymerization, surface hardness, marginal fit, wear resistance, transverse strength, transverse repair strength, surface roughness and polishability, color stability, and stain resistance. While certain materials exhibited advantageous properties in one or more of the tests, no one material was superior to the others in all tests. PMID- 2597303 TI - Education in prosthodontics: Britain, South Africa, and Australia. AB - The consultant in restorative density, Great Britain's closest equivalent to the prosthodontist in the United States, has a broad base of specialist training that includes periodontology, conservative dentistry, and prosthodontics. The dentist specialising only in prosthodontics is rare. British dental education has developed a curriculum that educates a dental provider to serve the needs of the British Health Service and as such has not emphasized prosthodontics as a separate discipline in either the undergraduate or graduate level. PMID- 2597304 TI - Prosthodontic education in the United States. AB - Prosthodontic education in the United States is well established and closely supervised by the American Dental Association, prosthodontic specialty organizations, and dental educators. Since the social and economic environment is rapidly changing in relation to medical care, it is incumbent that the prosthodontic community be willing to adapt new scientific and technical information to be able to continue to provide high-quality dental care. PMID- 2597305 TI - Besides yourself, what else are you selling? PMID- 2597306 TI - "Breastfeeding in Pakistan: thirty key questions". PMID- 2597307 TI - "Breastfeeding your baby". PMID- 2597308 TI - Linkages between immunization and breastfeeding promotion programs. AB - Breastfeeding promotion and immunization are important interventions of child survival programs, especially in developing countries. Linkages between breastfeeding promotion programs and the Expanded Programme on Immunization (EPI) in developing countries mean that health care workers can make use of every contact with the mother and child to reinforce the educational messages of both programs. Breastfeeding does not interfere with vaccinations administered in accordance with the routine schedule recommended by the EPI Global Advisory Group for use in developing countries. Breastfeeding benefits the EPI and the EPI also benefits breastfeeding. The maximum reduction of morbidity and mortality will be achieved when all child survival interventions are applied in a balanced, complementary manner as envisaged in the concept of primary health care. PMID- 2597309 TI - Recreational drug use by the breastfeeding woman. Part 1: Illicit drugs. PMID- 2597310 TI - MDL 72,974: a potent and selective enzyme-activated irreversible inhibitor of monoamine oxidase type B with potential for use in Parkinson's disease. AB - MDL 72,974, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine, was designed to be a selective inhibitor of monoamine oxidase type B (MAO-B). In vitro, the compound inhibits rat brain mitochondrial MAO in a concentration and time-dependent fashion and shows marked selectivity for the B form (IC50 = 680 and 3.6 nM for MAO-A and MAO-B, respectively). After oral administration to rats, the compound shows preferential inhibition of brain MAO-B with ED50 values of 8 and 0.18 mg/kg p.o. for the A and B forms, respectively. Selectivity is retained on repeat dosing. MDL 72,974 did not significantly potentiate the cardiovascular effects of intraduodenually-administered tyramine in anaesthetized rats and had only minor indirect sympathomimatic effects in the pithed rat. At MAO-B selective doses the neurotoxic effect of MPTP in mice was blocked. PMID- 2597311 TI - Platelet monoamine oxidase-B activity in Parkinson's disease. AB - Platelet MAO-B levels have been investigated in seventeen consecutively diagnosed and previously untreated patients with idiopathic Parkinson's disease using the non-hydroxylated catecholamine, beta-phenylethylamine, as substrate. Patients with Parkinson's disease had MAO-B activity levels that were considerably higher than sex and age matched normal controls or patients with Motor neurone disease or Myasthenia gravis. PMID- 2597312 TI - Endogenous urinary monoamine oxidase inhibitor excretion in Parkinson's disease and other neurological disorders. AB - In this study, urinary output of both neutral (tribulin) and basic monoamine oxidase inhibitory activity was measured in parkinsonian patients, other neurological patients and controls. No significant differences in output were found between these different groups. In general, tribulin output rose with age, in parallel with known changes in monoamine oxidase B activity. PMID- 2597313 TI - Enantiomeric composition of urinary salsolinol in parkinsonian patients after Madopar. AB - Urinary salsolinol output had been shown to be lower in Parkinsonian patients than in controls and to increase largely after L-dopa therapy. It had also been established that the R enantiomer of salsolinol is either the predominant or the sole enantiomer present in the urine of healthy subjects. When Madopar was administered to Parkinsonians, the enantiomeric composition of urinary salsolinol showed an S/R ratio around 1. Considering brain and plasma concentrations in dopamine, acetaldehyde and pyruvate, it is suggested that, under physiological conditions, urinary salsolinol should have a central origin in humans. Conversely, urinary salsolinol in Madopar-treated Parkinsonian patients might be predominantly formed at the periphery. PMID- 2597314 TI - The apparent autoxidation rate of catechols in dopamine-rich regions of human brains increases with the degree of depigmentation of substantia nigra. AB - The concentrations of the 5-S-cysteinyl adducts of dopamine (DA), 3,4 dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylalanine (DOPA) and the levels of noradrenaline (NA), DA, DOPAC and DOPA were determined in the putamen (PUT), caudate nucleus (CN) and substantia nigra (SN) of human post mortem brains with or without depigmentation and degeneration of the SN. The levels of DA, DOPAC and DOPA decreased with the degree of depigmentation and degeneration in the three brain regions while NA levels only decreased in SN and PUT. In general, the concentrations of the 5-S-cysteinyl adducts did not differ, but the ratios of 5-S-cysteinyl-DA/DA, 5-S-cysteinyl-DOPAC/DOPAC and 5-S-cysteinyl-DOPA/DOPA were higher in patients with a more depigmentated and degenerated SN, except for the 5 S-cysteinyl-DA/DA ratio in the PUT. Higher ratios were also found in the cell body areas compared to the neuron terminal areas. Thus depigmentation and degeneration of dopaminergic SN neurons, seem to be correlated to enhanced rates of autoxidation, possibly due to an impaired antioxidant capacity. PMID- 2597315 TI - The coenzyme nicotinamide adenine dinucleotide (NADH) improves the disability of parkinsonian patients. AB - The coenzyme nicotinamide adenine dinucleotide (NADH) has been used in an open label trial as novel medication in 34 patients with Parkinson's disease, using an intravenous administration technique. In all patients a beneficial clinical effect was observed. 21 patients (61.7%) showed a very good (better than 30%) improvement of disability, 13 patients (38.3%) a moderate (up to 30%) improvement. Concomitant with the improvement of the disability the urine level of homovanillic acid (HVA) increased significantly in all patients (in some patients by more than a 100%). The daily "on phases" of the patients could be increased from 2 up to 9 hours in the individual patients by NADH administration. PMID- 2597316 TI - [Herbalogic studies on the Chinese drug fangfeng]. AB - Through a critical study of the descriptions of Fangfeng in the ancient Chinese herbals, it may be concluded that the chief botanical source of this drug was Saposhnikovia divaricata, besides, the roots of Peucedanum ledebourielloides and P. wawrii may also be used. The root of Glehnia littoralis may be used as an substitute and called Shifangfeng. The difference in geographical sources of Fangfeng in ancient and present times is also discussed. PMID- 2597317 TI - [Pharmacognostic studies on the peel of Citrus reticulata Blanco cv. zhangshuensis and Citrus reticulata Blanco Var. kinokuni (Tanaka) H. H. Hu produced in Jiangxi]. AB - Pharmacognostical studies on the peel of Citrus reticulata cv. zhangshuensis and Citrus reticulata var. kinokuni have been carried out in comparison with four crude drugs of Chenpi. Information on the research of resources of these two drugs is provided. PMID- 2597318 TI - [Histology diagrams of crude botanical drugs]. AB - The paper summarizes the methods frequently used for drawing microstructural diagrams of botanical crude drugs with 80 tissue drawings. PMID- 2597319 TI - [Studies on the Oriental carpenten moth (Holococerus vicarious Walker]. AB - This paper deal with the harm done to Honeysuckle by the oriental carpenter moth. Based on a systematic investigation on the life history and habitude of the moth. We have found some effective measures for its prevention and control. PMID- 2597320 TI - [Quality evaluation of Panax quinquefolium L. introduced and cultured in China]. AB - An investigation was made on the shape, properties, tissue features, TLC identification and panaxoside content of the Panax quinquefolium introduced and cultured in China. The results showed that its quality was basically similar to that of the imported Panax quinquefolium. PMID- 2597321 TI - [Elimination of poison from Halitum violaceum by processing]. AB - The contents of polysulphides in different forms of Halitum violaceum (unprocessed, processed with vinegar, calcinated and boiled with water) were determined indirectly by UV spectrophotometry. The results showed that the unprocessed forms are higher in the contents of polysulphides while the processed ones have little or no such contents at all. It is thus believed that the poisons can be eliminated from Halitum violaceum by processing, which helps to decrease or eliminate polysulphides and sulphides. PMID- 2597322 TI - [Comparison of some trace element contents of Eucommia ulmoides Oliv. and its processed products]. AB - A comparison of the contents of 7 trace elements (Zn, Mn, Cu, Fe, Ca, P, Pb) in Eucommia ulmoides and its processed products has been made, and the significance of processing Eucommia ulmoides is discussed in light of the experimental results. PMID- 2597323 TI - [Studies on methods of processing sika deer fetus]. AB - Two methods of processing Sika Deer Fetus were comparatively studied according to the indexes such as rate of powder removal, crude proteins, crude fats, amino acids, trace elements, vitamins and hormones. It was found that the method of oven drying is superior to that of decocting. Thus we suggest that the former method should be used for Chinese patent medicines, such as Deer Fetus capsule etc. PMID- 2597324 TI - [Ultrafiltration properties in preparing injections of Chinese medicinal herbs using a J-48 ultrafilter]. AB - Four injections of single Chinese medicinal herbs and 3 medical solutions of pure substances showing impurities were prepared by J-48 ultrafilter. The retention rate of effective compounds and the clearance rate of impurity of each injection and solution before and after ultrafiltration were examined by a UV 265-FW Ultraviolet-spectrophotometer (Shimadzu, Japan). PMID- 2597325 TI - [Chemical constituents of Cordyceps mililaris (L.) Link]. AB - Six constituents were isolated from the hypha of Jinlin Cordyceps mililaris. The structures were determined to be beta-sitosterol, ergosterol, D-mannitol, daenine adenosine and cordycepin (3'-deopadenosine). Cordycepin, ergosterol, adenine were isolated for the first time from this hypha of Jinlin C. mililaris. PMID- 2597326 TI - [Antiarrhythmic effects of Cordyceps sinensis (Berk.) Sacc]. AB - The administration of 65% alcohol extracts of Cordyceps sinensis can counteract the arrhythmias induced by aconitine or BaCl2 in rats, and increase the tolerant dose of ouabain to produce the arrhythmias in guinea pigs. The drug can reduce the heart rate of anesthetic rats, decreasing the contractility of isolated papillary muscle or atria in guinea pigs, but showing no effect on the automatic rhythmicity and the functional refractory period of the atria. PMID- 2597327 TI - [Pharmacologic study of Curculigo orchioides Gaertn]. AB - The experiments showed that ethanolic extract of Curculigo orchioides had adaptive effects, such as enhancing tolerance towards high temperature and hypoxia. It also had sedative, anticonvulsant and androgen-like effect. Besides, it increased the immunological activity of mice. PMID- 2597328 TI - [Effects of Cymbopogon goeringii (Steud.) A. Camus volatile oil on physiologic properties of the isolated guinea pig myocardium]. AB - In isolated guinea pig papillary muscles and atrium, Cymbopogon goeringii volatile oil (CGCO) markedly inhibited the contraction, prolonged the functional refractory period (FRP) and depressed epinephrine-induced automatically. The results suggested that CGCO may possess antiarrhythmic action. PMID- 2597329 TI - The prevalence and incidence of dental calculus in adults. AB - The occurrence of dental calculus is widespread with various investigators having reported evidence of calculus accumulations in a vast segment of the population. The purpose of this paper is to provide information on both the prevalence and incidence of calculus formation among adults. To determine prevalence, a total of 1,426 adult males and females were graded in Indiana for the presence of calculus using the Volpe-Manhold (VM) Index on the lingual surfaces of the six mandibular teeth. A second panel of 980 subjects was recruited in Texas to determine the incidence of calculus over a six-month period. These latter participants were given a thorough dental prophylaxis, a sufficient supply of a sodium fluoride dentifrice and toothbrushes, and were instructed to use the dentrifrice as they normally do, at least once a day. Six months after the prophylaxis, 804 participants were available and were examined for calculus accumulation using the VM Index. Results from both clinical trials indicate that males have more calculus than females and calculus formation was directly related to age for both sexes. Data are presented regarding the frequency distribution of VM Index scores by sex and age. PMID- 2597330 TI - Reproductive and developmental toxicological evaluation of sanguinaria extract. AB - Reproductive and developmental toxicology studies were conducted with orally administered sanguinaria extract in rats and rabbits. Groups of animals which received no test article served as controls in all studies reported. No adverse effects on estrous cycling, male or female copulatory and fertility indices or gestation/lactation parameters were observed in rats given 10-100 mg/kg/day. Reduced body weights in the offspring during lactation were observed at the 100 mg/kg/day treatment level concomitant with maternal toxicity. No developmental toxicity, including teratogenicity, was observed on the fetuses of rats following maternal administration of 5-60 mg/kg/day. An increase in post-implantation loss was observed at maternally toxic dosage levels of 50 and 75 mg/kg/day in rabbits. Oral administration of sanguinaria extract in a perinatal and postnatal study in rats caused no adverse effects on litter size, parturition, or lactation of female rats nor on survival and growth of their offspring at dosage levels of 5 60 mg/kg/day. Maternal oral toxicity thresholds were 60 mg/kg/day in rats and 25 mg/kg/day in rabbits. It was concluded that the oral intake of sanguinaria extract has no selective effect on fertility, reproduction or fetal and neonatal development in rats or rabbits. PMID- 2597332 TI - Cariostatic effects of monofluorophosphate in solutions and dentifrices in rats. AB - The cariostatic effectiveness of dentifrices and solutions containing sodium monofluorophosphate (MFP) was evaluated in rats. In one study using 36 CARA rats, the caries inhibiting effects of sodium fluoride and MFP solutions, at equivalent soluble fluoride concentrations (750 ppm F), were compared. Both MFP and sodium fluoride significantly (p less than 0.01) reduced smooth surface caries by 78% to 81%, respectively. No significant differences between the two treatment groups were observed. In a second study, 5 dentifrices formulated with dicalcium phosphate dihydrate (DCPD) abrasive and different amounts of MFP (0, 250, 500, 750, and 1000 ppm F) were tested for cariostatic effects in CARA rats. Compared to the control groups, the MFP/DCPD dentifrices significantly (p less than 0.01) reduced smooth surface caries incidence by 66%, 81%, 76% and 85% at the 250, 500, 750, and 1000 ppm F concentrations, respectively. In each of the studies, both enamel fluoride content and molar surface solubility were measured. A third study assessed the compatibility of MFP with different abrasives and the effect of dentifrice composition on the release of MFP from a dentifrice slurry to a saliva phase. No differences in MFP release were observed for two different silica-based formulations which differed with respect to thickener, humectants and other ingredients. PMID- 2597331 TI - Clinical study to evaluate the effects of three marketed sugarless chewing gum products on plaque pH, pCa, and swallowing rates. AB - The purpose of this study was to determine the ability of three commercially available chewing gums (Extra, Trident, and CareFree) to stimulate saliva flow and reverse the plaque acid and ionized calcium levels induced by a glucose challenge. Electrodes to measure pH and pCa were situated in a Hawley appliance. When the Hawley appliance was in place, the electrodes were inserted into three day old plaque at maxillary interproximal sites. A pressure sensor, located in the posterior center of the Hawley appliance, was used to record swallowing rates. After baseline values were determined, the test procedure consisted of first administering a 5% glucose challenge solution followed by a 10 minute challenge effect period, a 5 minute gum chewing or product period, and finally a 10 minute product effect period after the test gum was discarded. An ANOVA was used to compare the ability of each chewing gum to stimulate saliva and cause a return of the plaque acid and/or ionized calcium to baseline levels following product discard. The three chewing gum products varied in both time and level of pH attained while neutralizing plaque acidity (p less than .05) induced by the glucose rinse. No significant differences were found between the chewing gums for the pCa data and swallowing rates. All chewing gum products stimulated swallowing and effectively reversed plaque pH and pCa changes caused by the glucose rinse. PMID- 2597333 TI - Determination by gas-liquid chromatography of trace amounts of soft polyvinyl chloride plastic additives in aqueous solutions. I. Epoxidized vegetable oils. AB - A gas-liquid chromatographic method for the determination of epoxidized vegetable oils (EVO), such as epoxidized soybean oil and epoxidized linseed oil, in aqueous solutions is described. The EVOs are extracted with n-hexane and transesterified to the methyl esters by sodium methoxide in methanol. 3% OV-210 is used as the stationary phase. The weakest standard solution corresponds to 5 micrograms/l (5 ppb) of EVO in an aqueous sample. The reproducibility of a single analysis is 5%. The method is used for the determination of EVO in intravenous fluids stored in flexible polyvinyl chloride bags. PMID- 2597335 TI - Effect of water content and type of emulgator on the release of hydrocortisone from o/w creams. AB - The release of hydrocortisone was determined in vitro from o/w-creams containing an anionic (sodium lauryl sulphate), a cationic (cetrimide) or a nonionic (cetomacrogol 1000) surfactant as emulgator and different amounts of water. The solubility of hydrocortisone in water-emulgator systems and the solubilizing capacity of these emulgators for hydrocortisone were also determined. The release of hydrocortisone from creams containing emulgators increased in the same order as the solubilizing capacity of these emulgators for hydrocortisone, which indicates how important the concentration of dissolved hydrocortisone in the cream is for release. The effect of water content on the release of hydrocortisone was also dependent on the emulgator used. With a nonionic emulgator, release was enhanced slightly as the water content in the cream increased. In the case of ionic emulgators, release of hydrocortisone was retarded as the amounts of water in the cream increased up to 60% water content; above this, the release was enhanced, probably owing to changes in the liquid crystalline microstructure of the cream. PMID- 2597334 TI - Effect of oleic acid on diffusion of drugs through hairless mouse skin. AB - The effect of oleic acid in propylene glycol or 2-ethyl-1,3-hexanediol vehicle systems on the skin permeability of 17 beta-estradiol, triamcinolone acetonide and trifluorothymidine was studied in vitro. The largest enhancement was obtained from a vehicle containing oleic acid in propylene glycol and the enhancement increased with increasing aqueous solubility of the drug. Oleic acid gave far less enhancement when propylene glycol was replaced by 2-ethyl-1,3-hexanediol. PMID- 2597336 TI - Prodrug forms for the sulfonamide group. IV. Kinetics of hydrolysis of N-sulfonyl pseudourea derivatives. AB - Two N-sulfonyl pseudourea derivatives, ethyl N-(p-tolylsulfonyl)-1 pyrrolidinecarboximidate and 3-butyl-2-ethyl-1-p-tolylsulfonylpseudourea, were prepared and evaluated as potential prodrug forms for the primary sulfonamide group in the model p-toluenesulfonamide. The stability characteristics of the compounds were examined in aqueous solution at various pH values as well as in the presence of human plasma and rat liver homogenate. The degradation of the derivatives was specific acid and base catalyzed, the maximal stability occurring at pH around 5. The products arising from the degradation included N ethoxycarbonyl p-toluenesulfonamide, an N-sulfonylurea as well as the parent p toluenesulfonamide. Human plasma did not significantly catalyze the hydrolysis and although some catalysis was observed in the presence of liver homogenate it is concluded that N-sulfonyl pseudoureas are too stable to be considered as a potentially useful prodrug form for the primary sulfonamide group. PMID- 2597337 TI - Inhibitory effect of extract of Ipomoea pes-caprae on guinea-pig ileal smooth muscle. AB - An extract of the plant Ipomoea pes-caprae, used in Thailand as a folk remedy for treating dermatitis caused by jellyfish and Portuguese man-of-war, has been tested for antagonistic activity against histamine, acetylcholine, bradykinin and barium chloride on the isolated guinea-pig ileum. The extract reversibly inhibited the contraction induced by all the spasmogens in a concentration dependent manner and decreased both the slope and the maximal response of the concentration response curves. It is not likely that the extract specifically interferes at the receptor level. It may be due to the direct action of the extract on the ileal smooth muscle. PMID- 2597338 TI - Determination by gas-liquid chromatography of trace amounts of soft polyvinyl chloride plastic additives in aqueous solutions. II. Di(2-ethylhexyl) phthalate, epoxidized vegetable oils and stearates. AB - A method for the determination of di(2-ethylhexyl) phthalate (DEHP), epoxidized vegetable oils (EVO) and stearates in aqueous solutions is described. A stepwise extraction procedure is employed to separate DEHP and EVO from the stearates, using n-hexane as extraction solvent. EVO is transesterified to methyl esters by sodium methoxide in methanol. The stearates are derivatized by methanol containing sulfuric acid. The alkyl esters are analyzed by gas-liquid chromatography, using 3% OV-210 as the stationary phase. The concentrations of the weakest standard solutions correspond to 10, 5 and 8 micrograms/l (ppb) of DEHP, EVO and stearates, respectively, in the aqueous samples. The method is used for the determination of DEHP, EVO and stearates in intravenous solutions stored in flexible polyvinyl chloride bags. PMID- 2597339 TI - Strategy and learning effects on perturbed movements: an electromyographic and kinematic study. AB - The effects of practice and movement strategy were studied in a goal-directed movement with different levels of perturbation applied in four independent groups (0%, 20%, 50% or 100%). The phase-plane trajectory data revealed that for all subjects there was a decrease in the mean trajectory variability with learning and that variability was affected by the level of uncertainty confronting the subjects. Both the average electromyographic (EMG) profiles and the mean subject variability for agonist and antagonist muscles decreased with learning. In each experimental group a specific interaction developed between reflex responses and voluntary activity to create a balanced level of EMG activity to improve the performance with learning. PMID- 2597340 TI - Seemingly paradoxical jumping in cataleptic haloperidol-treated rats is triggered by postural instability. AB - Paradoxically, animals exhibiting haloperidol-induced cataleptic immobility can be induced to leap vigorously, by pushing them forward from behind. It is shown here that such jumping can also be produced by placing them on a board and tilting it tail-end upward until about 50 degrees above horizontal. In both situations, jumps only occurred when the animal's hindlegs began to slip forward, as they lost their postural stability. As alternatives to jumping from the slope, rats turned to face upwards (negative geotaxis), or adopted a spread-eagled posture during head-first downward sliding, with the body and head flattened against the substrate. All 3 responses to the sloping board were present in some undrugged rats. Such rats, and those given low doses of haloperidol (0.5, 1.0 mg/kg), were more likely to turn upwards than to jump or slide. At high doses (7.5, 10.0 mg/kg), they were more likely to slide downward than to turn or jump. Jumping was most likely to occur at an intermediate dose (5 mg/kg), approximately 60 min after injection. We suggest that in the absence of haloperidol, and at low doses, locomotion is dominant over reflexes defending static equilibrium, and hence rats are more likely to turn upwards (which involves stepping). In contrast, at higher doses, locomotion is more fully suppressed, reducing the likelihood of turning. At very high doses of haloperidol and later in the action of the drug, muscle tonus appears to be weakened, reducing the likelihood of jumping. This possibility was supported by the finding that combined injection of the optimal dose of haloperidol and 2 mg/kg diazepam reduced the ability to cling vertically (suggesting weakness of muscle tone). In such rats, jumping from the sloping board was decreased, and active downward sliding was increased. Thus, different factors influence the occurrence of jumping at different doses of haloperidol. However, these are all active defensive responses to postural instability, and hence are similar to the other reflexes used by haloperidol treated rats to defend against displacement from static stable equilibrium, such as standing immobile, bracing, clinging, and righting. Jumping in response to loss of stability on the sloping board also occasionally occurred in undrugged rats. Unlike jumps by haloperidol-treated rats, those by undrugged animals only occurred when they could be directed to a safe landing place. Thus, if the board faced the edge of the table, so that the jump would carry the animal into space over the edge, undrugged rats either did not jump or jumped off the side of the board onto the table.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2597341 TI - Recovery from axial apraxia in the lateral hypothalamic labyrinthectomized rat reveals three elements of contact-righting: cephalocaudal dominance, axial rotation, and distal limb action. AB - In earlier work, we showed that in rats, proprioceptive-tactile information is sufficient for contact-righting on the ground (from lying on one side to prone). Thus, axial rotation, starting with the shoulders and followed by the pelvis, occurs normally in labyrinthectomized animals with eyes occluded. After damage to the lateral hypothalamus, even with labyrinths intact, contact-righting is at first abolished (1-2 days postoperatively), and when it reappears, involves pushing by the hindlegs. Rostrocaudal contact-righting, involving axial rotation, takes 3-4 days to recover. If labyrinthectomy is combined with lateral hypothalamic damage, the deficit is exaggerated and recovery is greatly slowed down, now requiring 2-3 weeks. The present paper shows that during this prolonged period of recovery several transitional forms of righting are present, each produced by a different combination of limb and body axis movements. At first, axial rotation is absent, and righting is achieved only by pushing with the limbs. This is followed by a transitional form in which, even though axial rotation cannot be triggered directly by contact with the ground, it can be triggered indirectly as an allied reflex when the paw places on the ground. Eventually the body axis actively initiates the rotation to proneness (at first, in the pelvis, later in recovery, in the shoulders), with the limbs being carried. Recovery of axial rotation overlaps with the recovery of cephalic dominance, yielding complex intermediate forms of righting. PMID- 2597342 TI - Comparison of retention performance between young rats with fimbria-fornix lesions and aged rats in a 14-unit T-maze. AB - Young (3-months) and aged (24-months) male F-344 rats were pretrained in one-way active avoidance in a straight runway for 3 days. Then two 10-trial daily sessions were given in a 14-unit T-maze in which the response requirement was to negotiate each of 5 maze segments within 10 s to avoid footshock. One day or one week after acquisition, bilateral electrolytic lesions were made in the fimbria fornix of young rats (1-day lesion or 1-week lesion). Corresponding sham operations were made for remaining young rats (1-day sham or 1-week sham). Aged animals did not receive any surgical treatment. One week after surgery, a 10 trial retention test was conducted to assess the lesion effects on retention and to manipulate the interval between acquisition and lesions. Aged animals were tested in the maze 1 week after acquisition. Results revealed that rats with fimbria-fornix lesions exhibited significant impairment compared to sham-operated groups on all retention performance measures including errors, runtime, number of shocks, duration of shock, and alternation errors. The number of errors and alternation errors of lesioned animals were still higher than those of sham operated animals at the second half of the retention test, whereas other non cognitive measures for lesioned animals recovered to control levels. The interval between acquisition training and lesions had no influence on retention performance. Although performance of aged rats during acquisition and retention trials was significantly worse than that of young controls and lesioned animals, a similar recovery pattern during retention testing was found for young rats with fimbria-fornix lesions and aged rats, i.e. both groups showed significant declines in non-cognitive measures with less decline in cognitive measures. These results suggest that the fimbria-fornix is partially involved in retention of 14 unit T-maze performance and that the age-related retention deficit observed in this task may be related to impaired transmission through this pathway. PMID- 2597343 TI - Effect of 5-HTP and ketanserine on the aggressive reaction induced by food competition in dominant and submissive pigeons (Columba livia). AB - There is abundant literature about the effects of manipulation of 5 hydroxytryptamine (5-HT) systems on some killer behaviors as well as on social isolation and shock-induced aggression in rodents. In this work we have analyzed the effect of 5-HT manipulation on the aggressive behavior induced by food competition in undernourished pigeons. Adult males (n = 12) were caged individually and their body weight kept at 80-85% by a restricted diet. These were divided in pairs which were exposed daily to an aggressive interaction test (20 min) in a 1.5 x 1.5 x 2.0 m chamber bearing a central feeding device. Once consolidation of dominance was obtained in each pair, the dominant and the submissive members were injected subcutaneously, on alternating days, with 5 hydroxytryptophan (5-HTP) (7.5, 15 and 30 mg/kg), ketanserine (20 and 30 mg/kg) and a combination of ketanserine (20 mg/kg) and 5-HTP (7.5 mg/kg). Aggression was evaluated by scoring the frequency and time spent biting, wing beating, aggressive following and vocalizations, threatening and pushing the opponent in 20-min tests. The time spent running away was also scored. Intratest feeding was ascertained by weighing the subjects immediately before and after testing. The scores were compared with those obtained after saline injection on the preceding day (C-scores). 5-HTP (7.5 mg/kg) attenuated aggression without affecting feeding in dominant members, and decreased the time spent running away by submissives. Higher doses of 5-HTP decreased feeding but did not potentiate the anti aggressive effects. The 5-HT2 antagonist, ketanserine did not affect aggression but decreased feeding at the dose of 30 mg/kg. Ketanserine injection clearly prevented the anti-aggressive effects of 5-HTP but caused a decrease of feeding. Results show that 5-HT stimulation in pigeons can preferentially block aggression in this particular experimental situation. It is suggested, in addition, that 5 HT2 receptors might be involved in such an effect. PMID- 2597344 TI - Cortical microvascular changes in chronological aging, cortical insults and chronic alcohol intoxication in rats. Effects of antihypoxic drug on these phenomena. AB - Chronic alcohol pulmonary exposure in rats produced a cortical hypervascularization from one to four weeks after the onset of the alcoholization procedure. This alcohol-induced cortical hypervascularization, resembling closely the enhanced cortical vascular network observed in chronologically aged rats as well as around a lesion-induced cavity performed on the cortex, was significantly reduced by a concomitant treatment with Sabeluzole, a chemically benzothiazol derivative with antihypoxic and antiischaemic properties. The blood alcohol level of rats treated with the antihypoxic agent remained stable and constant at a mean level of 1 g/l during a whole 2-week-alcoholization duration in contrast to that of untreated rats which was directly related to the increased alcohol concentration of the atmosphere insufflated in the alcoholization chamber. Finally, a free-choice paradigm achieved after the chronic intoxication also revealed that Sabeluzole-treated rats chose to drink less alcohol as compared to untreated rats suggesting Sabeluzole well modulated the alcohol-induced behavioral preference. PMID- 2597345 TI - Ethanol and inositol 1,4,5-trisphosphate mobilize calcium from rat brain microsomes. AB - The effects of ethanol on ATP-dependent Ca2+ uptake and inositol 1,4,5 trisphosphate (Ins-P3)-induced Ca2+ release were assessed in rat cerebellar and cortical microsomes. Ins-P3, 0.2-10 microM, released 7-14% of ATP loaded microsomal Ca2+ stores after a 15-sec exposure. Ethanol, 250-750 mM, added after ATP-dependent loading, significantly released microsomal Ca2+ stores, and the amount released was additive to that seen with Ins-P3 alone. The presence of ethanol, 250-750 mM, during the ATP-dependent loading period, resulted in decreased Ca2+ uptake that correlated with decreases in Ins-P3-induced Ca2+ release. Chronic ethanol treatment failed to produce any alterations in ethanol's ability to promote Ca2+ release or to inhibit ATP-dependent Ca2+ uptake. Furthermore, Ins.-P3-induced Ca2+ release was not altered by chronic ethanol treatment. These results suggest that Ins-P3 sensitive Ca2+ stores are resistant to pharmacologically relevant concentrations of ethanol, and do not appear to be involved in the chronic cellular effects of ethanol. PMID- 2597346 TI - Time-dependent effect of ethanol upon discrimination behavior. AB - The discriminative stimulus properties produced by ethanol were employed to demonstrate differences in discriminative performance over time in rats trained at different postinjection times. Thus, one group of rats was trained to discriminate between intraperitoneally administered 600 mg/kg ethanol and its distilled water vehicle at 6-min postadministration, whereas a second group of rats was trained to make this discrimination when trained at 30-min postinjection. Subsequent to reaching criterion performance, dose-response relations to doses of ethanol from 150-900 mg/kg were determined to be similar in both groups. This indicated that the discriminative stimulus effects at the two postadministration times were equally effective for training of behavioral responding to ethanol. The rats trained at 30 min postadministration maintained criterion level discrimination performance when tested at 6-, 15- and 60-min postinjection. In contrast, the rats trained at 6-min postadministration discriminated ethanol at a reduced level (40%) when tested at 30-min postinjection. These results suggest that the nature of the discriminable stimuli produced by a low dose of ethanol are different at 6-min and at 30-min postadministration. Evidence is cited to further suggest that the earlier stimuli are excitatory whereas the later stimuli are sedative. PMID- 2597347 TI - Methanol-induced monoamine changes in hypothalamus and striatum of albino rats. AB - This paper suggests that like ethanol, methanol also produces certain changes in the steady state level of monoamines in hypothalamus and striatum of albino rats. Though, the toxic manifestations of methanol are attributed to the metabolic end product of methanol viz. formic acid by several workers, we report here that the methanol-induced brain monoamine changes, at least, could be attributed to the direct action of methanol rather than to its metabolic end products like formaldehyde or formate. Studies in the steady state level of rat brain monoamines have shown that after methanol administration (3 g/kg), there is severe depletion of dopamine level in striatum but a significant increase in the level of dopamine, serotonin and 5-hydroxy indole acetic acid in hypothalamus. At the same time, norepinephrine and epinephrine levels are reduced in hypothalamus as well as in striatum. These effects do not seem to be induced by metabolic acidosis. The changes in monoamine levels are very well correlated with the blood and brain level of methanol as evidenced by maintaining a higher methanol level either by simultaneous administration of ethanol or by blocking methanol metabolism by pretreatment with 4-methyl pyrazole and 3-amino-1,2,4-triazole. It is thus postulated that monoamine changes induced by methanol appear to be the direct effect of methanol per se on the monoaminergic neuronal membranes. PMID- 2597348 TI - Inactivation of aldehyde dehydrogenase in intact rat liver mitochondria by dopamine. AB - Aldehyde dehydrogenase (EC 1.2.1.3) within isolated rat liver mitochondria was inactivated by incubation with dopamine. Concurrent with this inactivation, incorporation of radioactivity from 14C-labelled dopamine into three mitochondrial matrix proteins (subunit mol.wt. = 120,000; 54,000; 20,000 daltons) occurred. The 54,000 mol.wt. protein also interacted with antihuman mitochondrial aldehyde dehydrogenase antibody. Inactivation of aldehyde dehydrogenase by dopamine occurred more readily in females than in males. Use of monoamine oxidase (EC 1.4.3.4) inhibitors (deprenyl and clorgyline) partially protected against inactivation. Monoamine oxidase catalyzed conversion of to 3,4 dihydroxyphenylacetaldehyde only partially accounted for aldehyde dehydrogenase activity loss. PMID- 2597349 TI - Aldehyde dehydrogenase and monoamine oxidase in rat liver mitochondria. AB - Monoamine oxidase (EC 1.4.3.4) and aldehyde dehydrogenase (EC 1.2.1.3) activities were compared in the liver mitochondria of male and female rats. Monoamine oxidase activity using benzylamine as a substrate was significantly higher in males as compared with females: 1.45 versus 0.74 mumols/mg mitochondrial protein/hr, respectively. Monoamine oxidase activity using tyramine as a substrate and aldehyde dehydrogenase activity were the same in males and females. Monoamine oxidase-tyramine and aldehyde dehydrogenase activities did not vary with the different phases of the estrous cycle in the female but the activity of monoamine oxidase-benzylamine did; rats in the proestrous phase had the highest activity and those in the estrous phase had the lowest. PMID- 2597350 TI - Endoscopic findings in alcoholic liver disease: does gender make a difference? AB - Alcohol abuse and alcoholic liver disease are major health problems in many parts of the world. The prevalence of alcoholic liver disease is directly related to both rate and duration of alcohol intake. It is a widely held belief that women are more susceptible to the hepatotoxic effects of ethanol, and develop alcohol related liver disease more readily than do men. A lower volume of distribution for alcohol, greater immune reactivity and higher activity of alcohol metabolizing enzymes in women are considered, at least in part, to be responsible for the greater susceptibility of women to alcoholic liver disease. Little data exist as to the extent of gastrointestinal involvement in advanced alcoholic liver disease, and even less, as to the relationship of these potential gastrointestinal lesions with gender, and whether or not female patients develop gastrointestinal complications at an earlier time in their liver disease natural history and whether when it occurs it is more severe than that seen in males. To answer these questions, 75 subjects (49 men and 26 women) with alcoholic liver disease underwent elective upper and lower gastrointestinal endoscopy while they were clinically stable. The prevalence of the various gastrointestinal lesions did not differ significantly between male and female alcoholics except for gastric ulcer (GU) and nonspecific inflammatory changes of the colon which were more common in females than in males (23.1% vs. 6.1% and 11.1% vs. 0%, respectively; both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2597351 TI - Spontaneous versus elicited seizures following ethanol withdrawal: differential time course. AB - Ethanol withdrawal symptoms in clinical populations are observed to occur in unique clusters which differ in time of onset relative to the time of withdrawal and in their duration. Since periods of mild symptoms are sometimes observed between these clusters of more severe symptoms, the symptom clusters may reflect separate periods of hyperexcitability during which times different neuronal mechanisms are involved. To investigate this possibility in an animal model of ethanol withdrawal, rats were chronically exposed to ethanol in vapor inhalation chambers. Upon withdrawal from this exposure regimen, the time course of spontaneous seizure activity was observed for a period of 84 hr and compared to sensitivity to seizures elicited by audiogenic stimuli or by the convulsant drug picrotoxin. Spontaneous seizure events were observed to occur in clusters, and these clusters were differentially correlated with periods of increased sensitivity to induced seizure activity. These results further support the suggestion that seizure sensitivity during ethanol withdrawal may indicate the involvement of multiple, independent, neuronal mechanisms. PMID- 2597352 TI - Ethanol oral self-administration and rewarding brain stimulation. AB - The effects of orally self-administered ethanol (ETOH) on responding for rewarding brain stimulation were studied. Bipolar electrodes were implanted in either the lateral hypothalamic region of the medial forebrain bundle (MFB-LH) or the ventral tegmental area (VTA) of 6 male F-344 rats. After surgery subjects were trained in a continuous reinforcement procedure (CRF) for constant current rewarding brain stimulation. On alternate days subjects were allowed to drink an ethanol and sucrose solution (12% and 5%, respectively) for 30 min and subsequently tested on the brain stimulation procedure. All subjects showed facilitation of responding (increase in rate) after ingesting low to moderate doses of ETOH (0.4-1.7 g/kg). Depression of responding (decrease in rate) or return to baseline levels (control solution rate) was observed only in those subjects which ingested 2 g/kg or greater during the drinking period. These results indicate that low to moderate doses of self-administered ethanol will increase responding for rewarding brain stimulation. Further, the results suggest that this facilitation of responding is, at least in part, a function of the method of administration and/or the contingent nature of the ethanol delivery (self-administration). PMID- 2597353 TI - Long and short alcohol deprivation: effects on AA and P alcohol-preferring rats. AB - In contrast to all other strains of rats previously tested, the heavy-drinking AA rats were recently found not to increase their daily intake of alcohol after a week without ethanol. This result was now replicated with F52 generation male AAs using Wistars as controls. The same AAs, however, after being switched to a choice between 0.05% saccharin and water, showed a significant increase in saccharin drinking after being deprived of it for a week. Alcohol deprivation for 24 hr or less hardly affected the intake by Wistars during the first hour of renewed intake but sharply increased that by AAs. Still longer deprivation produced progressively smaller first-hour intakes in the AAs. Unlike the AAs, alcohol-preferring P rats showed an increase in alcohol drinking after a week of deprivation similar to that seen with normal rats. However, in common with the AAs, their first hour intake was increased significantly by only a few hours of alcohol deprivation. PMID- 2597354 TI - Early experience and the consumption of alcohol by adult C57BL/6J mice. AB - Two types of early experience were examined for their effect on voluntary alcohol consumption by adult C57BL/6J mice: the experiences associated with belonging to a particular litter, and the experience of early postweaning choice between water and a 10% alcohol solution. Males from identified litters were individually caged from arrival at three weeks of age and given a choice between 10% alcohol and water when eight weeks old. Another group without notation of litter was given alcohol-water choice upon arrival at three weeks of age. Alcohol intake was examined by three measures: daily licks of 10% alcohol, alcohol selection (percent alcohol drinking), and volume of alcohol drunk daily. Belonging to a particular litter did affect body weight and growth, but had no effect on adult consumption of alcohol. Postweaning exposure to alcohol choice, however, produced a small but significant and prolonged increase in alcohol consumption by adults. Furthermore, a developmental trend was found in mice offered alcohol choice at an early age: alcohol preference developed as postweaning growth slowed. PMID- 2597355 TI - Purification of human serum amyloid P component (SAP) by calcium affinity chromatography. AB - Serum amyloid P component (SAP) has been purified from human serum by means of immobilized metal ion affinity chromatography (IMAC). It was selectively concentrated on carboxymethylated aspartic acid agarose (CM-Asp-agarose) loaded with calcium and, employing very mild conditions, purified to electrophoretical and immunological homogeneity in a single step amounting to about 1900-fold purification. As a purification method our procedure thus compares well with bio specific affinity chromatography. PMID- 2597356 TI - Methotrexate loading of red cell carriers by osmotic stress and electric-pulse methods: ultrastructural observations. AB - Transmission and scanning electron microscopy (EM) of osmotically stressed and electrically pulsed human erythrocyte carriers indicated that the mode of uptake of methotrexate (MTX) varied depending on the method of carrier production. The preswell and electroporation loading methods, apparently by facilitating passive diffusion across the cell membrane, promoted incorporation of the MTX directly into the cytoplasm of the carriers, as evidenced by their variable electron densities. The preswell method produced carriers displaying leptocytic characteristics, whereas the electroporation method produced carriers exhibiting sphero- and stomatocytic transformation. Hypotonic dialysis-prepared carriers took up MTX primarily by endocytosis and secondarily by passive diffusion. Endocytotic activity was not induced by the MTX. Scanning EM revealed that most of the dialysis-prepared carriers exhibited prominent invaginations of the cell surface. Transmission EM of serial thin sections through these carriers revealed numerous fully internalized, membrane-bound vesicles. Endocytotic activity caused progressive loss of membrane and resulted in the sphero- and stomatocytic transformation of the carriers. PMID- 2597357 TI - Lactate dehydrogenase of concentric zones of human senile cataracts and calf lenses produced by ultrasound. AB - Cataractous lenses from men and women averaging 77.7 years of age were sonicated for intervals of 10 min with 0.85% saline under cooling in a laboratory sonicator, followed by centrifugation. The respective supernatants were analyzed for LDH and the weights of the zonal portions obtained by difference. The initial fraction averaged 60 and 47% in solids and LDH, respectively, with decreasing contents to the final harder core residue. The procedures were also applied to calf lenses. Much shorter sonication periods and stepwise increases in wattage from one fraction to the next were also investigated. The calf lens displayed higher LDH activity/mg at settings of 6-8 W in contrast to the cataracts, the initial fraction containing 80% of the enzyme activity and the solids; the values were far lower at settings of 1-3 W. As compared to the sonicated outer layer fractions, the calf nuclear portions showed small but significant decrements in the isoenzymes, LDH-1 and LDH-2, and increases in LDH-4 and LDH-5, possibly indicative of heightened anaerobiasis. PMID- 2597358 TI - Regional distribution of muscarinic and nicotinic cholinergic receptor binding activities in the human brain. AB - The distribution of nicotinic and muscarinic receptor subtypes was examined in human brain tissue obtained at autopsy from neurologically normal adult (50-60 years) individuals. Membrane preparations from 15 brain regions were examined for nicotinic (L-[3H]nicotine) binding, both M1 and M2 muscarinic receptor binding (distinguished on the basis of pirenzepine affinity) and high (H) and low (L) affinity muscarinic agonist binding (distinguished on the basis of carbachol displacement). Total muscarinic receptor binding sites were relatively high in striatal and cortical areas, where both M1 subtype and agonist binding type L predominated, compared with thalamic, nigral and cerebellar regions and spinal cord, where the M2 subtype and agonist binding type H predominated. Nicotinic receptor binding sites (predominantly high affinity, measured at low ligand concentrations) did not parallel any of the muscarinic subtypes, being concentrated in thalamic, neocortical and striatal regions. Scatchard analysis indicated the presence of both high and low affinity nicotinic sites, the numbers of the latter generally exceeding the former by over one order of magnitude. Neither muscarinic nor nicotinic receptor binding sites were closely related to the distribution of the cholinergic neuronal marker, choline acetyltransferase, suggesting that individual cholinergic pathways may be distinguished by the relative proportion of the different types of cholinergic receptors present. PMID- 2597360 TI - Immunohistochemical characterization of the sheep suprachiasmatic nucleus. AB - Using 19 antisera raised against neuropeptides, amines or enzymes of amine biosynthesis, an immunohistochemical characterization of the sheep suprachiasmatic nucleus was performed. The most distinguishing characteristic of the sheep suprachiasmatic nucleus was the low density of serotonin- and neuropeptide Y-immunoreactive fibres; their concentration was similar to that in surrounding areas. This is different from observations in rodents but similar to those in primates. Moreover, the sheep suprachiasmatic nucleus is also characterized by a dense plexus of methionine-enkephalin-immunoreactive fibres. This has not been observed in other species. As in other species, such as rodents, the sheep suprachiasmatic nucleus contains numerous neurophysin immunoreactive neurons and a few tyrosine hydroxylase-immunoreactive neurons. After colchicine pretreatment, many intensely stained vasoactive intestinal peptide-, vasopressin- and somatostatin-immunoreactive perikarya appeared, and more neurophysin-immunoreactive cell bodies were observed. Thus, although similarities exist among species, there are distinct differences in the neuro chemical organization of the suprachiasmatic nucleus in the sheep and other species. PMID- 2597359 TI - Distribution of serotonin-immunoreactive neurons in the brain of sockeye salmon fry. AB - The organization of the serotonergic cell groups in the brainstem of fishes and amphibians has received relatively little attention. It has been generally assumed that they are little differentiated and constitute a median cell column throughout the brainstem, and that laterally migrated serotonergic cell groups are largely lacking. In the present study we present evidence to the contrary. By the use of a sensitive immunocytochemical technique for the visualization of serotonin-immunoreactive (5HTir) neurons, we have been able to make a detailed delineation of the putatively serotonergic neuronal groups throughout the brain. In the epithalamus, 5HTir neurons were located in the left habenular nucleus in its dorsal subdivision. 5HTir neural elements, primarily photoreceptor cells, were present throughout the pineal organ and in some cases also in the parapineal organ. In the periventricular zones of the hypothalamus and posterior tuberculum, 5THir cerebrospinal fluid-contacting neurons were located in the paraventricular organ and in the dorsal, ventral and caudal zones of the periventricular hypothalamus. In the dorsal thalamus/synencephalon, 5THir neurons surround the tractus habenulo-interpeduncularis (fasciculus retroflexus). In the brainstem, several groups of 5HTir neurons could be discerned, that for reasons of topological similarity were named according to Lidov and Molliver a raphe pallidus/obscurus-complex (B1 and B2), raphe magnus (part of B3), median raphe (B8) possibly including raphe pontis (B5), raphe dorsalis (B4, B6 and B7), and B9. 5HTir neurons were observed in the central gray of the IVth ventricle, dorsal to the noradrenergic isthmal neurons and lateral to the brachium conjunctivum, in an area topologically equivalent with the dorsal subdivision of the locus coeruleus in mammals. In addition, small numbers of 5HTir neurons were located in the lobi faciales. Thus, the presence of well-differentiated groups of migrated serotonergic neurons is not an advanced trait of amniote brains, but may be a pattern common to all vertebrates. PMID- 2597362 TI - Benign cystic mesothelioma of the peritoneum--a case report. AB - A case of benign cystic mesothelioma in a 53-year-old woman is presented. The patient had abdominal pain and a palpable mass for 4 days. This mass was noticed incidentally by an obstetrician. A computed tomographic scan of the abdomen and pelvic sonography showed a cystic mass, 6 x 4 cm, in the right lower quadrant close to the cecum and suggested cystadenocarcinoma of the ovary. Operation showed that the mass involved peritoneum in region of the appendix. Complete removal of the mass was done. Grossly it consisted of multilocular cyst containing clear, serous, gelatinous fluid. The light microscopic examination revealed that this lesion consisted of cystic spaces of various size and intervening connective tissue stroma. The cells lined the cysts varied from flattened to cuboidal with occasionally a picket-fence or hobnailed appearance in areas. Brush borders were seen on the luminal surface of some cells. Electron microscopic examination confirmed that the cells were mesothelial origin. This lesion mimics cystic lymphangioma of the abdomen grossly and light microscopically, from which differential features are discussed. PMID- 2597361 TI - Acquired immune deficiency syndrome--report of an autopsy case. AB - Authors report the first autopsy case of acquired immune deficiency syndrome in Korea. The patient was a 26 years old Korean male who died of respiratory failure due to mixed pulmonary infections. He had history of homosexual contacts with partners of both domestic and foreign nationalities. Initial presentation was unexplained fever for two months. Serological test and western blot test for anti HIV were positive and T-cell subset analysis revealed T3/T4/T8 to be 73/8/67%. Pulmonary tuberculosis with mediastinal lymphadenopathy and esophagonadal fistula and oral candidiasis were presented. Respiratory infection progressed gradually and he died seven months after the initial symptom. Autopsy findings were generalized severe lymphoid cell depletion, especially of T-cell population and mixed pulmonary infections with Pneumocystis carinii and cytomegalovirus (CMV). The CMV infection involved lungs and adrenals. Oral candidiasis was also demonstrated. PMID- 2597363 TI - Responses of vasopressin release in patients with cardiopulmonary bypass anesthetized with enflurane and morphine. AB - Changes in plasma level of arginine vasopressin (AVP), arterial pressure, and urine flow were studied before, during and after cardiopulmonary bypass (CPB) in 11 patients with congenital heart disease. Anesthesia was induced with thiopental sodium (3-5 mg/kg) and was maintained with enflurane (1.0-1.5%), 50% N2O in O2 and morphine (0.5 mg/kg). Concentration of plasma AVP increased slightly from 3.8 +/- 1.5 pg/ml after induction and increased 3-fold after sternotomy. Plasma AVP level increased to 132 +/- 26 pg/ml and 218 +/- 54 pg/ml after 5 and 60 min on CPB, respectively. When the circulation returned to normal, plasma AVP level decreased gradually but was still significantly higher at 24 hr (13.4 +/- 2.5 pg/ml). Marked osmolar diuresis was induced with mannitol in the priming solution used during the CPB: increases in urine flow, Na excretion and osmolar clearance. Possible mechanisms of marked increase in AVP release and differences of AVP responses during CPB reported by other investigators are discussed. PMID- 2597364 TI - Central nervous system tumors among Koreans--a statistical study on 697 cases. AB - A total of 697 cases of intracranial and intraspinal tumors was obtained from the pathology file of Seoul National University Hospital and Children's Hospital during the period of 8 years from 1980 to 1987. These tumors were classified according to WHO classification. This study was performed to understand the recent trend of the relative frequency of the central nervous system tumors among Koreans and to compare it with the previous studies in Korea and other countries. There were 663 intracranial tumors and 34 intraspinal tumors. More common intracranial tumors were pituitary adenoma, meningioma, astrocytoma and medulloblastoma, each representing 23.4%, 20.8%, 11.8%, and 5.6%, respectively. In juvenile age group (under 15 years of age), medulloblastoma, astrocytoma, ependymoma and craniopharyngioma were more commonly encountered to be 25.6%, 21.6%, 13.6% and 12%, respectively. Both sexes were equally affected among adult group, but male preponderance was observed among juvenile group (1.49:1). Nine cases of primitive neuroectodermal tumor, a unique tumor which is not listed in WHO classification, were observed and all of them occurred before the age of 20. There were 27 metastatic tumors. Our previous study encompassing previous 17 years, 1963 to 1979, showed similar overall results except for intraspinal tumors that were more commonly encountered in previous series. PMID- 2597365 TI - Chronic progressive external ophthalmoplegia (CPEO) with 'ragged red fibers'--a case report. AB - Chronic progressive external ophthalmoplegia (CPEO) is a rare clinical syndrome characterized by slowly progressive paralysis of extraocular muscles. We report a male patient who had a 20 year history of CPEO. Histological examination of left deltoid muscle showed characteristic ragged red fibers. Electron microscopy revealed a number of abnormal mitochondria which contain paracrystalline inclusion bodies. PMID- 2597366 TI - Telangiectatic osteosarcoma--a case report. AB - Telangiectatic osteosarcoma is a rare and special variant of osteogenic sarcoma with distinct radiologic, gross and microscopic features. This tumor is predominantly lytic, destructive tumor without sclerosis on roentgenogram, and is soft and cystic on gross examination. Histologically aneurysmally dilated spaces lined or traversed by stromal cells producing osteoid are noted. This report concerns a case of telangiectatic osteosarcoma occurring in a 7 years old boy. He presented with pathologic fracture of the right distal tibia, followed by a purely lytic lesion on X-ray examination. This lesion recurred five times during a span of one year. Microscopic features of the biopsy specimen was difficult to differentiate from aneurysmal bone cyst because of prominant blood-filled cyst formation. It was finally identified as osteosarcoma from the below-knee amputation specimen through the close examination for anaplastic osteoid producing stromal cells in the septa that separate the blood cysts. PMID- 2597367 TI - Combined use of monochromatic and Laue diffraction techniques for macromolecular structure determination. AB - A novel strategy of macromolecular structure analysis is described which combines the use of monochromatic scanning Laue (SCL) and white-beam Laue (WBL) diffraction techniques. It provides, when applied with an area detector with on line capabilities, a means of interactively determining and optimizing experimental parameters; it further makes rapid data evaluation feasible, also with off-line detector systems. These new procedures have been applied to a protein structure, beta-trypsin, using a FAST area detector (Enraf-Nonius) and image plates (Fuji) on a double-focusing synchrotron beamline at DORIS. Structure factors, which were derived from FAST Laue data, were empirically scaled by comparing equivalent reflections in different wavelength bins. A 2Fo-Fc difference Fourier map, which was calculated at 1.8 A resolution using these structure-factor moduli together with phases from the known structural model, showed well defined electron density distribution (R = 22%). Image-plate exposures showed diffraction to 1.2 A resolution. The effect of crystal mosaicity on the maximum wavelength bandwidth for Laue exposures has been investigated. SCL techniques, which involve rapid scanning (with a crystal or multilayer monochromator or a tunable undulator) through a defined wavelength range, extend the applicability of Laue techniques to crystals with broadened mosaic spread. PMID- 2597368 TI - Application of molecular dynamics in the crystallographic refinement of colicin A. AB - Crystallographic refinement based on molecular dynamics (MD) has been applied to a 2.5 A resolution X-ray structure of the pore-forming fragment of colicin A. The crystallographic R factor was reduced from 48 to 23% with a concomitant improvement in stereochemical parameters. The method considerably speeded up the refinement process but was associated with some pitfalls. In particular, some badly fitted segments of the structure required manual rebuilding, even after MD refinement and some problems with weighting schemes were encountered. Analysis of the effects of the refinement and ideas for improvements are presented. PMID- 2597369 TI - Clinical evaluation of the handling properties of Herculite in posterior primary teeth. AB - This study evaluated the handling properties of Herculite compared to Dispersalloy in primary posterior teeth. The materials were evaluated with regard to differences in packing consistency, adhesion to instruments, ease of insertion, working time and ease of finishing the restoration. A total of 33 restorations (19 composite resin, 12 amalgam) were placed in nine children. The major impression achieved is that both materials have excellent handling properties. However, each material has its own place in the dentist's armamentarium. Posterior composite resins require a highly skilled and demanding clinical technique, which requires an appropriate professional fee and should not be seen as a replacement for the conventional alloy. PMID- 2597370 TI - Glass inserts. A new dimension in restorative dentistry. AB - Pediatric restorative dentistry has traditionally involved the placement of a stainless steel crown following a pulpotomy in primary molars. The increased exposure to systemic and topical fluorides has significantly decreased smooth surface caries, yet occlusal pit and fissure caries remains a problem. Occlusal caries involving the pulp of primary molars, leaving the supporting walls intact, may be restored conservatively with the use of glass inserts. The glass inserts provide the major volume of the restoration, therefore a minimal amount of posterior composite resin is necessary. The glass inserts bond to composite resin, increase restoration strength, and reduce polymerization shrinkage which may cause cuspal deflection or marginal microleakage. A case is presented to describe a new material and the conceptual protocol for clinical use. PMID- 2597371 TI - Non-surgical treatment of pseudo-recession in children and adolescents. AB - A case of a 7 year-old girl with gingival pseudo-recession at a mandibular permanent central incisor was successfully treated with a non-surgical approach. Patient compliance (oral hygiene), the location of the junctional epithelium in relation to the cemento-enamel junction (pseudo or true recession), the width of the buccal alveolar bone of the affected tooth, the potential for an increase in the width of the attached gingiva and tooth alignment should be taken into account when considering the type of treatment (surgical or not) of uneven buccal gingival margins in children and adolescents. PMID- 2597372 TI - Multiple supernumerary teeth. Report of two cases. AB - Multiple supernumerary teeth scattered in both jaws are reported in two patients. In the young patient, all supernumerary premolars were found to be at different stages of crown development and in the adult patient, all supernumerary teeth had fully formed roots. PMID- 2597373 TI - Metallic dental restorations. A performance survey. AB - A radiographic survey was conducted to assess professional performance in restorative dentistry. Analysis of 629 proximal metallic margins of restorations revealed a significant level of imperfection. The discrepancies at the gingival margins were measured on a tracing of the restoration using a grid and a Boley gauge. The results were consistent with other data. Contributing factors which explain this phenomenon are offered as well as considerations for the profession regarding the review of care quality. PMID- 2597374 TI - Clinical evaluation of etched porcelain veneers. AB - This study evaluated 115 etched porcelain laminate veneers placed by a single operator at New York University Dental Center between 1982 and 1985. The restorations were divided into two groups. Group I consisted of 43 restorations placed without any tooth preparation; Group II consisted of 72 restorations placed using a chamfer preparation. The U.S.P.H.S. criteria was used to record cavosurface marginal discoloration, marginal integrity, and presence of caries. A clinical examination also revealed the number of debonds and/or the number of fractures of porcelain. A periodontal evaluation included the use of baseline and recall stone replicas of restored teeth to measure the height of the free gingival margin taken mid-facial to the incisal edge of the restoration. Any changes in gingival contour were also noted. Plaque and gingival indices were also recorded. The low fracture and debond rate found in the study combined with no incidence of caries seem to indicate that these restorations are functioning satisfactorily and with minimal negative periodontal response. PMID- 2597375 TI - The sympathoadrenal system: friend and foe? PMID- 2597376 TI - Hypertension: the noradrenergic factor. Proceedings of a symposium. PMID- 2597377 TI - AIDS tops dentists' concerns. PMID- 2597378 TI - More adults seek ortho care as teeth are kept longer. PMID- 2597379 TI - Implant specialty necessary to meet prostheses demand. PMID- 2597380 TI - Chronic pain seen as vexing to diagnose. PMID- 2597381 TI - Bugs & drugs are out; root canal prep is in. PMID- 2597382 TI - Bioengineering advances early perio detection. PMID- 2597383 TI - Women gain authority as more enter profession. PMID- 2597384 TI - Hygienists: first stop in preventive care. PMID- 2597385 TI - AIDS virus bred in mice. PMID- 2597386 TI - Ascend twelve steps to controlled asepsis. PMID- 2597387 TI - One-appointment endodontics, sonic instruments discussed. Interview by Dr Phillip Bonner. PMID- 2597388 TI - Cleaning essential to post-root canal healing. PMID- 2597389 TI - Guidelines help with deciding on cements. PMID- 2597390 TI - The apicoectomy myth: failures need surgery. PMID- 2597391 TI - Exit, hiring procedure key to retaining staff. PMID- 2597392 TI - When to prep or not to prep: three cosmetic dentists debate. PMID- 2597393 TI - Creating illusions is vital in aesthetic dentistry. PMID- 2597394 TI - Proper antibiotic use basic to good dentistry. Interview by Phillip Bonner. PMID- 2597395 TI - Cement-mixing tips presented. PMID- 2597396 TI - Climb six steps to a top infection control program. PMID- 2597397 TI - The secret to busyness is a boomerang practice. PMID- 2597398 TI - Infection control compliance: albatross is becoming SOP. Interview by Phillip Bonner. PMID- 2597399 TI - Seeing is believing. PMID- 2597400 TI - Dentofacial aesthetics poses puzzles teamwork can solve. Interview by Phillip Bonner. PMID- 2597401 TI - Bone classification, training keys to implant success. PMID- 2597402 TI - Good leadership skills make top less lonely. Interview by Hugh Doherty. PMID- 2597403 TI - Avoid computer liability with ample staff training. PMID- 2597404 TI - Periodontal health is maintained next to non-prepped laminates. PMID- 2597405 TI - Magnification is major aid to dentists ... and now microdentistry's time has come! PMID- 2597406 TI - Marginal adaptation of composite resins and dentinal bonding agents. PMID- 2597407 TI - Etched porcelain restoration uses expanded beyond facial veneers only. PMID- 2597409 TI - Simplified shade selection makes work easier, better. PMID- 2597408 TI - Research proves new light cured ionomer stronger. PMID- 2597410 TI - [Care "objectives"]. PMID- 2597411 TI - [Perspectives in ethics in oncological nursing care]. PMID- 2597412 TI - [A nurse who loves statistics!]. PMID- 2597413 TI - [Developments in health care. Primary Health Care. A decoy--or a reality?]. PMID- 2597414 TI - Cytoplasmic pH is regulated in isolated avian osteoclasts by a Cl-/HCO3- exchanger. AB - Osteoclast resorb bone in an acid compartment formed by the bone-attachment site. The low pH of the resorption compartment provides a lysosome-like milieu suitable for acid proteases to degrade collagen. Solubilization of the hydroxyapatite that makes up bone mineral consumes about 2 moles of protons per moles of calcium dissolved, requiring a massive proton flux to maintain a low pH in the resorption compartment. In order to determine how the osteoclast maintains a physiological cytoplasmic pH while secreting massive amounts of acid, we studied the intracellular pH of osteoclasts using esterified fluorescein derivatives while controlling the electrolyte composition of the medium. The principal finding is that osteoclasts have a high capacity for chloride/bicarbonate exchange which enables them to maintain normal intracellular pH in the face of a large loading of base equivalents. Thus, the overall process of proton secretion during bone resorption is similar to the polarized acid elimination by renal epithelia, involving a proton pump on one surface of the cell, and a Cl-/HCO3- exchange to maintain cytoplasmic pH. PMID- 2597415 TI - Regulation of podosomes by intracellular pH in avian osteoclasts. AB - The effects of changes in intracellular pH (pH1) on the organization of the clear zone of isolated avian osteoclasts in culture were studied. The distribution of podosomes, the close contact areas that mediate the adhesion of osteoclasts to the substrate, was investigated by decoration of microfilaments with fluorescent phalloidin. Intracellular acidification by butyric acid induces significant increase of podosome formation at the level of the clear zone compared to controls. Conversely, alkalinization by HCO3- reduces the percentage of osteoclasts with podosomes. A role of pH1 on the adhesion of the osteoclasts to the substrate is hypothesized. PMID- 2597416 TI - Growth of bone marrow CFU-GM in a case of cyclical neutropenia. Preliminary report. AB - We studied bone marrow CFU-GM growth behaviour of a 9-year-old male child with cyclic neutropenia. The cultures were performed on day 0 and on day 13 of cyclic oscillation, in order to study some correspondences between CFU-GM culture parameters and the phases of a whole cyclic oscillation "in vivo". We explored the CFU-GM growth under three different conditions of GM-CSA production: a) standard source of CSA; b) endogenous GM-CSA assay; c) GM-CSA-gamma-globulin assay. At both observation times the endogenous GM-CSA assay produced more aggregates than the baseline culture. The GM-CSA-gamma-globulin assay partly corrected the growth increase, produced by endogenous assay. At time 0, at the nadir of peripheral blood neutrophils, there was a balance between the number of aggregates, appeared early in culture and early degenerated, and those appeared late. From progenitor cells culture performed on day 13 of cycle, a week before the zenith of neutrophils in vivo, we obtained an increase in aggregates, which appeared late. The values of CFU-GM grown from the culture performed on day 13 reached higher levels than the ones performed on day 0. The CFU-GM growth behaviour shows that in our case with cyclic neutropenia there is no defect in progenitor cells, while on the contrary there is an increase in CSA production. PMID- 2597417 TI - [Further observations and considerations on the biological and reproductive cycle of the roe buck (Capreolus capreolus L.)]. AB - The authors have studied the seasonal microanatomical modifications of the ovary of the roe deer and testis of the roe buck. The ovary during the month of September presents primary, secondary and mature vesicular follicles. During the month of October there is the first presence of a corpus luteum. The corpora lutea during the months of November and December increase in size and blood supply; the cells are filled with acidophil granules. The corpora lutea persist also in January and February when embryos are implanted in the uterus. This result agrees with Short's and -Hay's but differs from that of Stieve. Testes show the first spermatogenic activity during the month of April. The spermatogenesis is completed in June, persists and reaches the top during July and August, when the Leydig cells acquire a strong acidophil cytoplasm. Indeed the spermatogenesis decreases during September and October; then, during winter months the testes are devoid of all signs of spermatogenic activity, the tubules being lined only be Sertoli cells and spermatogonia. PMID- 2597418 TI - [Projections of the Tsai tegmental ventral area to the hippocampus: a study of the rat using the Fink-Heimer technic]. AB - The projection from the ventral tegmental area of Tsai (VTA-A10) to the hippocampal formation was investigated in the rat by means of the Fink-Heimer technique, after VTA destruction by electrolytic lesion or local injection of 6 hydroxydopamine (6-OHDA, 1 micrograms/0.5 microliters). Degenerated fibers are prevalently present in the ventral subiculum and CA1 field. These areas match with the area projecting towards the nucleus accumbens. Thus the dopaminergic meso-cortico-limbic pathway could modulate the HF-striatal projection which represents a link between the limbic and central motor systems. PMID- 2597419 TI - [Organization of the direct projections of the Tsai ventral tegmental area to the hippocampus]. AB - In this report we have examined the distribution in the ventral tegmental area of Tsai (VTA-A10) of the neurons projecting to the hippocampal formation (HF) by injecting, in different combinations, retrograde fluorescent tracers (Fast Blue, 2% and Nuclear Yellow, 1%) in several hippocampal areas. The distribution of the VTA labeled neurons suggest a topographic organization of the VTA efferent pathway towards the HF. These results are in agreement with the concept that precise topography of the projections is a distinctive feature of the dopaminergic systems in general. PMID- 2597420 TI - [The discriminant function of an early prognostic index in the monitoring of cranial trauma]. AB - A method for statistical evaluation of a prognostic index in head injuries (I.P.T.C.) is described. This index, obtained by the sum of results of clinical and cerebral electrophysiologic tests was precociously carried out on 53 head injured subjects. A multiple regression formula, furnished with better discriminant power than experimental I.P.T.C. is suggested. PMID- 2597422 TI - [The color of drugs: a preliminary survey]. AB - An inquiry has been conducted on the colours considered more suitable for four kinds of drugs. In general, while light colours are indicated for antianxiety and sleep-inducing drugs, bright colours are indicated for antidepressant and tonics. PMID- 2597421 TI - DNA damage induced by some bile acids, evaluated with alkaline elution technique. AB - Bile acids are promoting agents in colon carcinogenesis. In this work we have tried to characterize the DNA alteration induced by bile acids in Sprague-Dawley male rats. Confirming previous findings, a clear increase in elution rate was observed at alkaline pH. No effect could be observed when the nuclei were washed before the elution, in condition totally unsuitable for the repair of the type of DNA damage induced by typical genotoxic agents. We advanced the hypothesis that the increased alkaline elution rate observed with bile acids could be independent of DNA fragmentation and related to changes in chromatin structure. PMID- 2597423 TI - The hexose transporter of human erythrocytes in aging and Alzheimer dementia. AB - The hexose transporter protein of human erythrocyte membranes was investigated in aging and in demented patients with Alzheimer disease (AD) and Parkinson disease (PD) by assessing the D-glucose-displaceable binding of the ligand cytochalasin B. We found no alteration in the hexose transporter of erythrocyte membranes in aging or in dementia of AD and PD. These findings indicate that the marked decrease in the density of hexose transporter that we previously reported in the cerebral cortex and brain microvessels in AD do not occur in erythrocyte membranes that have the highest density of the hexose transporter protein. PMID- 2597424 TI - A study of the reliability of the family history method in genetic studies of Alzheimer disease. AB - The reliability between 2 raters conducting independent family history interviews for Alzheimer disease-like and other dementias was investigated. The interviews were conducted at least 1 year apart with the second rater blind to the data collected by the first rater. Raters agreed on the presence and type of dementia in 153 relatives age 45 or older of 30 AD probands, the age at onset in secondary cases, and the age of nonaffected relatives. PMID- 2597425 TI - Diagnostic steps of dementia in the commentary by C.G. Gottfries. PMID- 2597426 TI - A population survey on legislative measures to restrict smoking in Ontario: 3. Variables related to attitudes of smokers and nonsmokers. AB - A telephone survey of 1,383 residents of Ontario was conducted to assess attitudes toward antismoking legislation and knowledge of active and passive smoking health effects. After estimation of population parameters, analyses were carried out separately in smokers and nonsmokers to determine which characteristics, if any, were related to positive and negative attitudes, higher or lower knowledge scores, and predicted compliance or noncompliance with restrictive measures. Both bivariate and multivariate analyses were carried out. This paper reports the results for several measures of attitudes including restrictions on smoking locations and sales, differential insurance rates, control of advertising, and increase in taxes on cigarettes. Identification of smokers who hold negative attitudes is more reliable than identification of nonsmokers who hold positive views. Because different sets of variables were found to be related for the different attitude measures, it may be necessary to design different kinds of programs to prepare individuals for changes in legislation. The companion paper on p. 323 reports on the results for knowledge of active and passive smoking health effects and predicted compliance. PMID- 2597427 TI - A population survey on legislative measures to restrict smoking in Ontario: 4. Variables related to knowledge of active and passive smoking health effects and to predicted behavior of smokers and nonsmokers. AB - Results from the further analysis of a population survey on legislative measures to restrict smoking revealed that identification of subgroups of smokers is more reliable than identification of subgroups of nonsmokers when a variety of attitudes were the measures of interest. A similar pattern emerged when analyses were carried out on knowledge of active and passive smoking health effects and on predicted personal and general compliance. Because distinct sets of variables were found to be related to distinct outcomes, program planning for changes in knowledge and behavior might, of necessity, have to be different. Media messages might be useful for changes in knowledge, while actual experience might be more important for attitude and behavior change. PMID- 2597428 TI - Coronary heart disease risk assessment. AB - A coronary heart disease (CHD) risk assessment was conducted on 883 patients enrolled in two primary-care rural practices in western Maryland to evaluate the relationship among presence of cardiovascular disease, major risk factors, and self-perception for CHD among the clients. Patients with preexisting cardiovascular disease other than peripheral vascular disease were more likely to perceive themselves at increased risk. However, 16% (39/246) regarded themselves to be at below average risk. These patients tended to have lower income, education, and anxiety levels. Nineteen percent of patients without preexisting cardiovascular diseases regarded themselves to be at above average risk. These patients tended to be disabled, unemployed, and have increased anxiety levels. Regardless of the presence or absence of preexisting cardiovascular disease, a patient's self-perceived risk was not altered significantly by the presence of one or more risk factors other than a positive family history of CHD. Based on Framingham risk profiles, 7.3% (29/395) of the white patients 35-74 years of age without preexisting cardiovascular disease had scores of 0.301 and above. Women had 1.4 times lower estimates of risk compared to men. The discrepancy that can occur between perceived and actual risk for CHD among a significant percentage of patients attending a primary-care rural practice underscores the importance of ascertaining both prior to prescribing risk reduction interventions. PMID- 2597429 TI - Addressing unanswered questions about population cholesterol screenings: the Model Systems for Blood Cholesterol Screening Program. AB - Elevated blood cholesterol is one of the three major modifiable risk factors for heart disease. Almost 60% of adults in the United States have an elevated blood cholesterol level, yet most adults are unaware of their level. The National Heart, Lung and Blood Institute (NHLBI) and other organizations have now recommended that all adults be tested to assess their blood cholesterol level. New portable blood cholesterol analyzers have recently been designed and are being promoted widely for cholesterol screening. However, there are many unanswered questions about the reliability of these devices and about the usefulness of mass cholesterol screening programs. The Model Systems for Blood Cholesterol Screening Program, an NHLBI-funded effort consisting of three research projects designed to provide a systematic evaluation of these devices and of mass cholesterol screening, is described. This research will contribute to a data base from which recommendations regarding public cholesterol screening will be made. PMID- 2597430 TI - Outrunning the risks: a behavioral risk profile of runners. AB - There is a need to assess better the relationship between physical activity and other health behaviors through population-based studies. Using the state-based Behavioral Risk Factor Surveillance System, we examined the behavioral risk factors of smoking, alcohol use, hypertension detection, obesity, seat-belt use, and physical activity in 2,412 runners and 26,538 nonrunners. Our analyses demonstrated marked differences in behavioral risk profiles between runners and nonrunners. Runners, regardless of the amount of running, were more likely to be nonsmokers, be of normal weight, be normotensive, and regularly use seat belts than were nonrunners of similar age and sex. Patterns of alcohol use were not different when comparing male runners with male nonrunners. However, female runners were more likely to drink and drive and to use alcohol on a chronic basis compared to their nonrunning counterparts. The "runner's lifestyle" may convey a certain level of protection from chronic disorders that are associated with these risk factors. However, further prospective studies are needed to examine in more detail the relationship of running to the risks and/or benefits for improved health. PMID- 2597432 TI - Evaluation of antileishmanial activity of trans-aconitic acid. AB - TAA, an inhibitor of the enzyme aconitase, inhibits the growth of L. donovani promastigotes. Morphogenic transformation of the amastigote to the promastigote (table; see text) form in vitro was also inhibited by 2 mM TAA. TAA also reduced multiplication of the parasite in macrophage culture. In the hamster model of leishmania, TAA significantly reduced the parasitic burden of liver. In acute toxicity tests with BALB/c mice no deaths were recorded even at a dose level of 2 g/kg body wt/day. PMID- 2597431 TI - Improving preventive care at a medical clinic: how can the patient help? AB - We developed a comprehensive individualized preventive care reminder system and then tested the hypothesis that directly involving patients in the reminder process would lead to greater use of preventive services than involving physicians only. There were three experimental groups of 350 patients each: in group 1 physicians and patients received the reminder; in group 2 physicians only received the reminder; in group 3 neither physicians nor patients received the reminder. Nine preventive care services were studied: blood pressure measurement; dental exam; ocular pressure measurement; stool exam for occult blood; influenza, pneumococcal, and tetanus vaccinations; mammography; and Papanicolaou smears. Need for these services was determined by telephone interview and chart review. To determine whether services were obtained, charts were reviewed after four to eight months of follow-up. For overall compliance with preventive recommendations and for several individual services (stool exam for occult blood, tetanus vaccination, mammography), group 1 patients received significantly more preventive care than group 2. Likewise, group 2 patients received more preventive care than group 3. These data show that involving patients in reminder efforts is an effective means of raising the level of preventive services. PMID- 2597433 TI - Skin wound healing in riboflavin deficiency. AB - Healing of excision and incision wounds was evaluated in riboflavin-deficient rats. The period taken for the epithelialization of excision wounds was 4 to 5 days longer in riboflavin-deficient animals compared to ad libitum-fed or food restricted weight-matched control groups. Riboflavin deficiency as well as food restriction slowed the rate of wound contraction, the effect of riboflavin deficiency being of greater magnitude. The tensile strength of incision wounds in riboflavin deficiency was reduced to 42% of the ad libitum-fed control and 63% of the weight-matched control values. There was a decrease of 25% in total collagen content of incision wounds, in riboflavin deficiency and its maturity was drastically affected as indicated by a twofold increase in salt solubility (1 M NaCl) and a four-fold increase in the alpha/beta subunit ratio of salt-soluble collagen. Food restriction had similar effects but of lower magnitude. The data suggest that alteration in collagen content and maturity may be responsible for the lower tensile strength of incision wounds in riboflavin-deficient rats. This suggestion was supported by the results of a rehabilitation experiment. PMID- 2597434 TI - Total glycosaminoglycans in the plasma of adults: effects of age and gender, and relationship to plasma lipids: a preliminary study. AB - Plasma glycosaminoglycans and lipids have been measured in the plasma of 92 fasted males and females. In the males, glycosaminoglycans correlated significantly with age (r = 0.39), triglycerides (r = 0.44), and cholesterol (r = 0.30). When the effect of age was allowed for, the significance of the correlation between glycosaminoglycans and triglycerides was maintained (r = 0.36). Glycosaminoglycan levels are higher in females than in males. The correlation of glycosaminoglycans with age in women was only marginally significant. In both men and women the effect of age is attributable principally to an increase in glycosaminoglycan concentration in those over 54 years. The only lipid fraction correlating with glycosaminoglycans in females was VLDL cholesterol (r = 0.34) and by stepwise linear regression allowing for the effect of age, this significance was retained (beta = 0.34). PMID- 2597435 TI - Studies on the mechanism of acetaldehyde-mediated inhibition of aspartate aminotransferase (GOT) in human erythrocytes. AB - The mechanism of acetaldehyde-mediated GOT inhibition was studied in human red cells. In the GOT assay mix, acetaldehyde competitively inhibits activation of apoGOT by pyridoxal phosphate and pyridoxamine phosphate. However, Ki values are 100-1000 times greater than Km values for these B6 vitamers. Moreover, incubation of undiluted lysates with acetaldehyde at 37 degrees inhibits GOT activity without increasing apoGOT levels and without altering affinity of apoGOT for either B6 coenzyme. In undiluted lysates, inhibition is not prevented by disulfiram. However, incubation at 4 degrees prevents both acetaldehyde metabolism and GOT inhibition while preincubation with NaF prevents GOT inhibition without affecting acetaldehyde disappearance. The effect of NaF is completely reversed by pyruvate but only partially reversed by NADH. Glyceraldehyde 3-phosphate, the only glycolytic intermediate which directly inhibits GOT, does not reverse the NaF effect. Thus, inhibition of GOT by acetaldehyde (a) requires nonoxidative metabolism of acetaldehyde and (b) is not mediated either by glycolytic substrates or by impaired binding of B6 vitamers to the GOT apoenzyme. Since NaF had no effect on a lysate deficient in glucose 6 phosphate dehydrogenase, the hexose monophosphate shunt may play a role in acetaldehyde-mediated GOT inhibition. PMID- 2597436 TI - Influence of monosaccharides on the fibrillogenesis of type I collagen. AB - The in vitro self-assembly of Type I rat tail tendon collagen in the presence of monosaccharides was studied turbidimetrically. D(+)glucose and D(+)mannose delayed fibril formation significantly while D(-)fructose showed no variation. The effect of glucose was concentration dependent. Binding of glucose during fibrillogenesis was shown by the incorporation of [14C]glucose and also by SDS polyacrylamide slab gel electrophoresis of the product. The results indicate that in vitro nonenzymatic glycosylation can take place in the short duration required for fibril formation. PMID- 2597437 TI - Serotonin- and catecholamine-related substances in the brain of ornithine transcarbamylase-deficient Sparse-fur mice in the hyperammonemic state: comparison of two procedures for obtaining brain extract, decapitation and microwave irradiation. AB - Increased flux through the 5-HT pathway during hyperammonemia was indicated by a significant positive correlation between Gln concentration and the ratio of 5 HIAA to 5-HT in the brain of spf mice taken after microwave irradiation to prevent postmortem changes in metabolites. There were no significant changes in the catecholamine pathway in the brain during hyperammonemia despite the increases in Try and Phe. PMID- 2597438 TI - 1-Methyladenine in urine of an adenosine deaminase-deficient adult without immunodeficiency. AB - Procedures are described for the isolation and identification of 1-methyladenine from the urine of an adult female with adenosine deaminase deficiency but no immunodeficiency. Evidence is provided indicating that much of the usual urinary excretion product, 1-methyladenosine, is converted to 1-methyladenine in this subject prior to excretion. Since the nucleoside phosphorylases present in normal individuals do not act on 1-methyladenosine, this suggests that a phosphorylase with unusual properties is present in this adenosine deaminase-deficient subject. A possible role for this phosphorylase in removal of deoxyadenosine in this subject is discussed. PMID- 2597439 TI - Thirty-five years of progress. ASAIO 1989. PMID- 2597440 TI - An autologous connective tissue tube with high healing ability as a small diameter vascular substitute with temporary antithrombogenicity. AB - Although autologous connective tissue grafts (ACTG) are an ideal vascular substitute, they have not yet been used as small diameter vascular grafts because of thrombogenicity. We reported on ACTGs in which mesh tubes were fabricated from ultra-fine polyester fibers (UFPF) and used as a framework. Antithrombogenicity was established using an original heparinization method, with a 50% patency 1 month postimplantation. Early failure of these grafts was caused mainly by loss of antithrombogenicity before development of endothelialization on the inner surface. In this study, higher concentrations of heparin were used for in situ heparinization of the grafts before implantation in combination with antiplatelet therapy (cilostazol, OPC-13013 for the first month after substitution for canine carotid arteries. As a result, more complete healing of the grafts was attained, with a patency rate of 63% at 1 month, when small doses of antiplatelet agents were used. More intensive antiplatelet therapy resulted in impairment of graft healing, causing hematomas around the grafts. Thus, optimal doses of antiplatelet agents remain uncertain. PMID- 2597441 TI - Concentration profiles of 1 and 2.5 microns beads during blood flow. Hematocrit effects. AB - Freeze-capture techniques were used to obtain concentration profiles of 1.0 and 2.5 microns latex beads in suspension flows with hematocrits from 15 to 60%. Profiles with near-wall concentrations more than twice the central concentration occurred for 2.5 microns beads in this range of hematocrits, but the near-wall excess appeared wider and shorter in 60% suspensions. For suspensions with 1.0 microns beads, the nature of the profile was dependent upon hematocrit. In all cases, at least a small near-wall excess was observed. For hematocrits of 40 and 60%, profiles for 1.0 microns beads were sometimes similar to those for 2.5 microns beads. For the 60% hematocrit and small beads, however, the excess was less than twice the central concentration in two of five trials. These findings are discussed in the context of previous experiments. PMID- 2597442 TI - Imaging analysis of platelet deposition on the extracardiac valved conduit in humans. AB - In 14 patients (aged 2-29 yr) with Hancock (n = 11) or Carpentier-Edwards extracardiac valved conduits (n = 3), platelet deposition (PD) was investigated using indium 111 (111In) platelet imaging. Repeated studies were performed in five patients. By visual analysis, 71% (5/7) of the imagings (7 images/5 patients) showed PD at early study 1-3 months after surgery, 9% (1/11) at intermediate study at 6-46 months (mean 21 mon) (11 images/10 patients) and 0% at late study at 81-132 months (3 images/3 patients). Quantitative analysis was made using relative ratio of radioactivity at the graft area to the area of the brachiocephalic artery (platelet accumulation index or PAI). The PAI was 1.85 +/- 0.47 (mean +/- SD) at early study, 1.51 +/- 0.23 at intermediate, and 1.36 +/- 0.37 at late study (NS). There was no significant difference in the late pressure gradients across the conduit (16-68 mon postoperatively) between the two groups with (n = 3) and without (n = 5) PD at the early stage (1-18 mon postoperatively, n = 8). The result may indicate that PD to the valved conduit in the right ventricular (RV) outflow tract occurs early postoperatively (mostly within 3 mon). The relationship of the PD detected by this method to late obstruction was not clarified in this study. PMID- 2597444 TI - Aortocoronary bypass grafting with hydrophilic small caliber vascular grafts. AB - Previous work showed that the authors' vascular graft had satisfactory antithrombogenicity because of high hydrophilicity. The authors developed a small caliber xenograft using new technology and evaluated the potential application for aortocoronary bypass grafting. Fresh sheep carotid artery with an internal diameter of 3 mm was obtained, and cross-linked with hydrophilic polyepoxy compounds. A 6 cm segment of the graft was then used between the aorta and the left circumflex coronary artery without cardiopulmonary bypass in 17 dogs. Sodium heparin was given during the surgery, but no anticoagulant was used thereafter. After the surgery, the dogs were randomly assigned to two groups according to the observation period. In 11 animals (Group 1), the observation period was up to 24 hr, at which time the grafts were evaluated; the patency rate was 72.7%. The patent grafts were clean and without thrombi. At the distal anastomotic lines of the occluded grafts, a thrombus was observed and a technical error was highly suspected. In six dogs (Group 2), angiography was performed to confirm graft patency between 2 and 3 weeks. The patency rate was 50% during the mean observation period of 17.5 days. One graft was evaluated at postoperative day 23. It was patent and soft, and the inner surface was shiny and smooth. Microscopic observation showed nice healing characteristics. These results indicate that it is possible for this new graft to be used for aortocoronary bypass grafting. PMID- 2597443 TI - Absence of rejection in cryopreserved saphenous vein allografts for hemodialysis. AB - Since November 1987, a total of 16 dialysis patients in the authors' Center, received a cryopreserved saphenous vein allograft (CSVA) as "third choice" vascular access. ABO and HLA-A-B compatibilities were determined but not considered. Saphenous veins were cryopreserved in liquid nitrogen for variable periods (1-6 mo), so that there was the opportunity to choose the most suitable in dimension. In February, 1989, a total of 13 patients retained a well functioning access site, whereas three had died from causes unrelated to CSVA. Because rejection of venous allografts still is debated among angiologists, recipient T lymphocyte subsets (CD3-CD4-CD8 and CD4/8) were examined, as were lymphocytotoxic antibodies, before and on days 15 and 30 after implantation. No evidence of immunologic activation was found. Moreover, in 10 of 16 patients the surgeons subcutaneously implanted a fragment of CSVA, and an immunohistochemical study was carried out using an alkaline phosphatase-antialkaline phosphatase (APAAP) technique and a panel of monoclonal antibodies. Minimal infiltration of the outer layer of adventitia was found, mainly caused by monocyte macrophages (Leu M3+) with few T lymphocytes (CD3+). The authors conclude that rejection is not a major cause of failure in CSVA in dialysis patients. PMID- 2597445 TI - A comparison of the antiplatelet effect of aspirin on human and bovine platelets. AB - The risk of thromboembolism in human patients or animal models with blood contacting prosthetic devices is well documented. Aspirin is used frequently as an antiplatelet agent to minimize this risk. Although the inhibitory effect of aspirin on human platelets has been clearly established, preliminary studies to examine this effect on bovine platelets revealed a minimal inhibition of platelet function in vivo as well as in vitro. Because a considerable amount of implant research is carried out in bovine models, it was considered important to evaluate carefully the antiplatelet effect of aspirin on bovine platelets. To evaluate the effect of aspirin, experiments were conducted on human and bovine blood in vitro as well as after the administration of aspirin up to 4,000 mg/day (p.o.) in calves and 2,500 mg/day in humans. Appropriate amounts of buffered aspirin were added to heparinized or citrated blood incubated for 25 min and centrifuged to obtain platelet rich plasma (PRP). An aliquot of PRP was then challenged by a predetermined concentration of ADP (an aggregating agent) or collagen to evaluate platelet aggregation and release reaction. After aspirin was administered in vivo, blood was drawn from the animal at predetermined intervals to evaluate platelet function. In human blood, the inhibitory effect of aspirin was discernable at 80 mg/L in vitro and 2,500 mg/day when ingested orally. Under identical experimental conditions, no inhibition of bovine platelet aggregation was observed using dosages of aspirin up to 1,000 mg/L in vitro or 4,000 mg/day in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2597446 TI - Laser vascular welding in biologic grafts. AB - This study evaluated the possibility and efficacy of laser welding in biologic vascular grafts. Grafts were anastomosed to 21 canine peripheral (femoral and/or carotid) arteries or coronary arteries with a Nd-YAG laser using the contact method. The laser welds were fashioned using 1-1.5 W power for 1-3 sec. The grafts used were heparinized canine carotid artery cross-linked with polyepoxy compounds. The welding was a success in 92% (22/24) of the peripheral artery and 83% (5/6) of the coronary artery procedures. The early patency rate was 100%. The anastomotic sites were strong enough to withstand high pressure (more than 300 mmHg of arterial pressure). Histologic examination was performed on days 0 and 3, 1 week, 3 weeks, or more than 1 month postoperatively to compare the progression of healing. The laser welded sites had a smooth external surface and minimal damage of the internal layer, with minimal inflammatory response and no pathologic granulation. The welded sites fused strongly after 1 postoperative week. In conclusion, an Nd-YAG laser, using a contact method, could successfully weld peripheral and coronary arteries to biologic vascular grafts. PMID- 2597447 TI - Clinical trial of a self-sealing PTFE-silicone dialysis graft. AB - A double wall PTFE graft with a silicone rubber middle layer (PTFE-sil) shown in a canine model to be self-sealing after needle puncture, was tried in 30 dialysis patients. Thirty-five patients with PTFE grafts were controls. All patients were followed for 1 year. In the PTFE-sil group, mean time to first dialysis was 1.3 days after implantation; during first 10 treatments, 17% of punctures did not bleed, 61% bled minimally, and 4% required 10 or more minutes of compression. No bleeding complications were encountered at any time. Complications of PTFE-sil vs. PTFE were as follows: thrombosis 36.6% vs. 28.5%; infection 13.3% vs. 11.4%; seroma 3% vs. 0%; steal 3% vs. 0%; pseudoaneurysm 0% vs. 17.1%; one year primary patency 63% vs. 66%; secondary patency 75% vs. 67%. In conclusion, the PTFE-sil graft, can be used immediately after implantation, sparing patient additional access procedures for acute dialysis. This results in less morbidity, decrease in bleeding complications, considerable shortening of hospital stay and significant reduction in expenses. PMID- 2597448 TI - Performance of a new vascular xeno prosthesis. AB - To date no prosthetic vascular prosthesis performs as well as the autologous saphenous vein in diameters of 6 mm and less. The purpose of this study was to compare the in vitro and in vivo performance of a new glutaraldehyde stabilized, narrow diameter (4 mm), vascular prosthesis fashioned from bovine ureters (Flonova) with the saphenous vein and polytetrafluoroethylene (PTFE) prostheses. The methods used for the comparative in vitro analysis of the bovine ureter and saphenous vein were modifications of tests recommended by the American National Standards for Vascular Prostheses. Blood compatibility was evaluated by measuring platelet consumption in an artificial circulation, and heparin uptake was quantified using tritiated heparin. The results indicate that the bovine ureter grafts have an adequate degree of mural integrity and hemocompatible properties comparable to saphenous vein. The in vivo patency in a canine bilateral femoral interposition model was 62.5% (10/16) for the bovine ureters and 43.75% (7/16) for PTFE. Bovine ureter grafts appear to have an excellent potential for use in narrow diameter peripheral and coronary arterial bypass procedures and warrant further investigation. PMID- 2597449 TI - Photochromic visualization for investigation of artificial heart valves. AB - This report contains results of investigation into hydrodynamics of artificial heart valves by means of photochromic flow visualization (PFV). The PFV method is based on activation of colored tracers in originally colorless photochromic solutions by pulse laser radiation during 10(-6)-10(-9) sec. PMID- 2597450 TI - Experimental studies on an artificial esophagus for the purpose of neoesophageal epithelization using a collagen-coated silicone tube. AB - An artificial esophagus was fabricated from a collagen-coated silicone tube 5 cm long, with an inner diameter of 2.5 cm and a wall thickness of 1 mm. The outer surface was coated with dry collagen to 5 mm thickness. The bilayered prosthesis was anastomosed to the cervical esophagus of adult mongrel dogs that were fed only by intravenous hyperalimentation (IVH) with 80 cal/kg/day and 60 ml water/kg/day for 3 weeks after the operation. Once the dogs began to consume food orally, the artificial esophagus dropped spontaneously into the stomach and formation of the neoesophagus was complete. Macroscopically, the neoesophagus showed no evidence of leakage or inflammation and had a smooth internal surface, but it developed slight segmental narrowing. Microscopically, layers of stratified squamous epithelium covered the neoesophagus within 3 to 4 weeks. The most characteristic feature of the artificial esophagus was that the replacement prosthesis did not remain in the esophagus after healing. Esophageal epithelization extended into the collagen layer coating the silicone tube and a new esophageal lumen was regenerated, thereby decreasing the chance of infection and leakage. However, neoesophageal stenosis was observed when the silicone tube was removed. PMID- 2597451 TI - The effect of graded exercise on cardiac output of the Jarvik-7-70 total artificial heart in humans. AB - Animal exercise studies have shown a self-regulated change in cardiac output (CO) with the J-7 total artificial heart (TAH). A 49-year-old, 75 kg patient received a J-7-70 TAH as a bridge to transplant. During bicycle exercise, the TAH heart rate, drive pressures, percent systole, and vacuum were unchanged. Cardiac output was measured by analysis of diastolic air exhaust. Mean arterial pressure (MAP) was measured via a radial artery catheter. Daily recordings of hemodynamics were made from TAH day 35 to 56 at rest, cycling with zero resistance, 18 watts resistance, return to zero resistance, and at rest. Values were as follows: baseline MAP, 75.7 +/- 9.7; LCO, 6.4 +/- 0.2; RCO, 6.8 +/- 0.2. For zero watts resistance MAP was 92.2 +/- 7.2*; LCO, 7.1 +/- 0.2*; RCO, 7.8 +/- 0.3*. For eighteen watts resistance MAP was 101.3 +/- 6.2*; LCO, 7.6 +/- 0.3*; RCO, 8.4 +/- 0.4*. For zero watts resistance MAP was 98.5 +/- 4.9*; LCO, 7.2 +/- 0.4*; RCO, 8.0 +/- 0.4*. The postexercise MAP was 86.4 +/- 4.1*; LCO, 6.2 +/- 0.2; RCO, 6.9 +/- 0.2. For all but baseline and postexercise MAPs, the average response was over a 4 minute interval. The starred values were significant compared to baseline p less than 0.05. Exercise resulted in an autoregulated change in TAH CO in man. Increasing the work of exercise produced an increased CO, reflecting changes in venous return. A TAH patient can exercise for more than 30 minutes with an autoregulated CO and no deleterious effects. PMID- 2597452 TI - Characterization of natural and total artificial heart acceleration. AB - The pulsatile nature of an implanted total artificial heart (TAH) may have several deleterious effects. To define the level of TAH impact, acceleration was measured and compared with that of the natural heart in a series of in vivo and in vitro experiments. In TAH implantations in calves, miniature accelerometers were incorporated onto the housing of a Utah-100 left ventricle. Identical accelerometers were glued to felt pledgets to obtain measurement of radial cardiac acceleration when sewn to the epicardial surface of the natural heart. Measurement of natural and artificial heart acceleration was made both intraoperatively and postoperatively in several animals. Many pumping conditions were also investigated with a similarly instrumented UVAD 85 left ventricle during in vitro testing. The peak natural heart acceleration measured was nearly 2 g both intraoperatively and at rest. Treadmill exercise or epinephrine infusion produced twice the resting peak acceleration value of the natural heart. Artificial heart peak acceleration as great as +/- 100 g was found intraoperatively and postoperatively. Peak TAH acceleration could be reduced by allowing the ventricle to fill fully prior to the start of the next systole, by allowing the ventricle to fully eject prior to the next diastole, or by using a ventricular pressurization waveform that has a smooth contour with a sinusoidal like profile. The ability to lower TAH acceleration may lead to a reduction in undesirable consequences of TAH implantation. PMID- 2597453 TI - Hematologic abnormalities and thromboembolic complications in calves implanted with pneumatic artificial hearts. Long-term studies and autopsy findings. AB - The purpose of this study was to assess hematologic abnormalities and thromboembolic complications related to long-term use of the pneumatic artificial heart (PAH). Laboratory data and autopsy findings were analyzed from 24 calves that survived 70-353 (150 +/- 82) days after implantation of a PAH. Compared with baseline levels, the hemoglobin was significantly lower, and the plasma hemoglobin and serum LDH significantly higher, throughout the follow-up period. The platelet count decreased during the first 10-30 weeks, but returned to preoperative levels by week 35. Platelet survival in 4 calves in stable condition was normal, and the leukocyte count and absolute neutrophil count were within normal limits. At autopsy, thrombotic complications and organ infarction were noted in 13 calves, and major septic complications were documented in 10 animals. The authors' observations indicate that thromboembolism and infection are major complications of long-term use of the PAH. PMID- 2597454 TI - Mechanism of dialysis-induced hypotension. AB - Using a hematocrit monitoring system and a Swan-Ganz catheter, the authors investigated the changes in blood volume and hemodynamic parameters before, during, and after dialysis-induced hypotension. When hypotension occurred, the cardiac output dropped sharply, and there were concomitant sudden decreases in the mean pulmonary arterial pressure and the mean right atrial pressure. These are attributed to a decrease in venous return. Since there was no recognizable change in blood volume when the blood pressure fell sharply, decrease in the venous return is considered to be caused by relocation of circulating blood, possibly associated with a sudden decrease in venous tone. PMID- 2597455 TI - Transcellular urea gradients cause minimal depletion of extracellular volume during hemodialysis. AB - Concern exists that increasingly high-efficiency dialysis will result in large urea gradients between intracellular and extracellular compartments (VI, VE) leading to large amounts of extracellular volume depletion (delta VE) and hemodynamic instability induced by rapid water flow from VE to VI. The authors investigated this question with a two-compartment model that provided estimates of VI, VE, and osmotically active intracellular and extracellular urea and nonurea concentrations during hemodialysis. The authors found that the urea gradient-induced transcellular water shift is only a very small fraction of VE, even with high urea clearance and short hemodialysis time. The net water shift was small because the urea and nonurea transcellular osmolar gradients were of similar magnitudes but in offsetting directions. PMID- 2597456 TI - Changes in blood volume during dialysis are dependent upon the rate and amount of ultrafiltrate. AB - Actual circulating blood volume during dialysis therapy can be monitored by continuous hemoglobinometry. Using this method in 15 stable, clinically nonoverhydrated dialysis patients, blood volume was recorded applying different modes of ultrafiltration: constant ultrafiltration (less than 500 ml/hr); high initial (greater than 1,500-2,000 ml/hr), subsequently decreasing ultrafiltration; and intermittently high (greater than 1,500 ml/hr) ultrafiltration. Mean amount of ultrafiltrate in all patients was 3,400 ml. Mean decrease in blood volume by 20% was generally tolerated without a decrease in blood pressure. Irrespective of the different modes of ultrafiltration, a decrease in blood volume was dependent only on the amount of ultrafiltered fluid. A constant, low ultrafiltration rate was not superior to a high ultrafiltration rate. In stable dialysis patients, decrease in blood volume is dependent only on the amount of ultrafiltrate. Up to a 20% decrease in blood volume, fluid can be removed from the patient even at a rate of 2,000 ml/hr. PMID- 2597458 TI - Reasonably short hemodialysis time can be achieved without ultra-high efficiency dialyzers and without ultrafiltration-controlled delivery systems. AB - To evaluate the ability to provide short hemodialysis (less than 9 hr per week) without the requirement for costly ultra-high efficiency dialyzers and ultrafiltration control delivery systems, 69 patients maintained on chronic hemodialysis were studied. Standard dialysis was delivered with bicarbonate dialysate, Baxter CF 1211 dialyzers, QB = 300 ml/min, mean time 215 min. The mean KT/V was 1.16. Hemodialysis prescription was changed to maintain the KT/V unchanged. Time was decreased by increasing urea clearance by increasing the QB (400 ml/min in 65 patients, 350 ml/min in 4 patients) and employing the Baxter CF 2308 dialyzer. This produced an increase in urea clearance from 192 ml/min to 256 ml/min, and a decrease in duration of dialysis to 164 min. The CF 2308 dialyzer has an ultrafiltration coefficient of 4 ml/mmHg/hr, which is easily managed without ultrafiltration control equipment. Patients were in the study group for a mean of 176.5 days. The short period of time caused no significant change in blood urea nitrogen, creatinine, potassium, bicarbonate, calcium, phosphorus, hematocrit, or symptomatic hypotension and vomiting. Patient acceptance of the change in hemodialysis time was excellent. Hemodialysis times similar to those reported by others with large experience in shortening hemodialysis time can be achieved in many instances with standard hemodialysis equipment. PMID- 2597457 TI - Plasma histamine levels and kinetics in chronic hemodialysis patients. AB - Pruritus is frequently observed in hemodialyzed patients; its etiology seems to be multifactorial. Increased plasma histamine levels have been reported in chronic renal failure. As histamine is a potent inducer of pruritus. The authors investigated its concentrations and kinetics in plasma of stable hemodialyzed patients. PMID- 2597459 TI - Fall of cholesterol with time on dialysis: impact on atherogenicity. AB - The majority of patients treated for chronic renal failure die from cardiovascular complications. Lipid abnormalities in this group are thought to contribute to this high mortality. The authors have shown that hemodialysis patients with longer months on dialysis tend to have lower total cholesterol (TC) levels. This study extends data to examine lipid disturbances in 53 continuous ambulatory peritoneal dialysis (CAPD) and 126 hemodialysis patients using multivariate analysis. Longitudinal values after 9-10 months were measured in 16 CAPD patients and 52 hemodialysis patients. Analysis of covariance for all patients demonstrated an inverse correlation of TC (p = 0.003), high-density lipoprotein (HDL) cholesterol (p = 0.01), and apolipoprotein A-I levels (p less than 0.02) with months on dialysis. In addition, the TC level was higher in women (p less than 0.001) and CAPD patients (p less than 0.001), and correlated with age (p = 0.02) and albumin (p less than 0.001). HDL cholesterol was higher in blacks (p less than 0.001) but was not affected by gender, dialysis modality, age, or albumin. Diabetic status, serum parathyroid hormone, and blood pressure were not significant variables for TC or HDL-C. The atherogenic risk indicators, TC/HDL cholesterol (p less than 0.001) and apolipoprotein B (p less than 0.02) were higher in whites than in blacks. Longitudinal study revealed lower TC levels in individual hemodialysis patients (p less than 10(-6) by paired t-test), the fall being greater for patients with fewer total months on dialysis (p less than 0.04, by analysis of covariance). CAPD patients had no change in TC by paired t test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2597460 TI - A simple and compact total artificial heart for temporary use. AB - Thromboembolism and anatomic fit are the major issues to be addressed in the design of a heart replacement device for total circulatory support. In an attempt to overcome these problems, a simple 70 mm3 displacement pusher plate, low pressure, pneumatically driven TAH was developed for temporary use. For optimal anatomic fit, easy implantation, and better flow patterns, the 5.7 X 10.7 cm total artificial heart (1) TAH was made of two essentially flat pumps integrated into a single unit. This single package approach avoids the dead space that occurs between the two pieces of conventional TAH and thus minimizes overall volume. It was designed to be positioned in the pericardial sac in a fashion similar to the natural ventricles and, based upon previous anatomic studies, fit in the average sized adult patient. In contrast to conventional free diaphragm pumps, the diaphragms of this TAH are supported by pusher plates that have a unique guide mechanism at the center to ensure a linear-controlled diaphragm motion and consequent uniform blood flow distribution. The guide of each pusher plate nests into the other, resulting in minimal thickness of the package. By using a simple displacement transducer, reliable output monitoring, with the possibility of selection of various pumping modes and adjustment of stroke volume, is possible. The authors anticipate this efficient and practical TAH to be a suitable temporary heart replacement device. PMID- 2597461 TI - One year's experience using a rotating filter for therapeutic plasma exchange. AB - The authors previously demonstrated the feasibility of using a rotating filter system for therapeutic plasma exchange. They now report on the technical details of a 1 year clinical experience. Seventeen patients underwent 188 treatments. Hemoaccess was provided by antecubital veins (147 Rx), femoral catheters (37 Rx), or an a-v fistula (3 Rx). Blood flows ranged from 75 to 100 ml/min. Net plasma removed per treatment was 3,231 +/- 53 ml (mean +/- SE, n = 188). Mean plasma removal rate per treatment was 40.2 +/- 0.6 ml/min; mean treatment time was 83 +/ 2 min. Platelet counts before and after treatment revealed a 15 +/- 4% decline (n = 46 Rx). Despite filtration fractions up to 86% there was no evidence of significant membrane plugging or hemolysis. For semiselective removal of cholesterol, the rotating filter was used in a cascade system with a secondary filter. Eighty percent of processed plasma was returned to the patient, but the treatment time was prolonged by 37% and the total cholesterol removed was 26% less when compared with the single pass system. The authors conclude that an inexpensive rotating filter can provide a highly efficient plasma exchange. The inherent efficiency of this system must be considered when evaluating its use with secondary filtration techniques. PMID- 2597462 TI - The effect of neutrophil depletion on reperfusion arrhythmias during intracoronary thrombolysis using the leukocyte removal filter. AB - To evaluate the effects of neutrophil depletion on reperfusion arrhythmias using a leukocyte removal filter (LRF), the authors examined several cardiovascular variables in three patients with myocardial infarction who underwent successful thrombolytic therapy with LRF compared with control patients without LRF. Coronary angiography performed within 4 hr of onset revealed total occlusion in the proximal segment of the left anterior descending (LAD) coronary artery, without collaterals, in all patients. Thrombolysis was performed by intracoronary administration of urokinase (10,000 IU/ml, 1,000,000 IU total) mixed with filtered autologous blood. LRF was composed of a nonwoven polyester fabric (1.8 microns, 4.6 g). Removal rates of leukocytes and platelets by LRF were 98-100% and 98%, respectively. Average duration of the ischemic episodes, maximum ST segment elevation, and integral of T segment depression did not differ in the two groups. However, the frequency of ventricular premature beats (VPB) during the first 30 min after reperfusion were significantly lower in the LRF treatment group (3.8%) compared with the control group (10.7%). Segmental shortening, measured by echocardiography one hour after recanalization, exhibited higher values in the LRF treated patients than control patients, without significant difference. Data suggested that LRF is effective in reducing reperfusion arrhythmias during intracoronary thrombolysis and activated neutrophils may play an important role in stunned myocardium. PMID- 2597463 TI - Long-term evaluation of a growable graft. AB - The safety of a vascular graft that can grow with the growth of its recipients was evaluated during long-term implantation in experimental animals. An acellular matrix made of human saphenous vein was cross-linked with a polyepoxy compound to give controlled biodegradability, hydrophilicity, and antithrombogenic properties. Four millimeter internal diameter (ID) grafts, enveloped with a polyester mesh tube of 10 mm ID were implanted in 15 puppies. The diameter of the graft grew to 9.5 mm after 1 year from the original 4 mm, and remained stable for 2 years and 7 months of observation. The newly formed neointima reinforced with polyester mesh was composed of smooth muscle cells covered with endothelial cells. The original vein graft was completely absorbed, and there were no degenerative changes such as calcification or aneurysmal dilatation. The graft maintained the expected size. PMID- 2597464 TI - A simple method for rapid and precise estimation of the protamine dose required for clinical heparin reversal. AB - A simple, colorimetric protamine titration method was developed for rapid and precise estimation of the protamine dose required for clinical heparin reversal. The method employs azure A dye as the titration indicator, and has replaced the time consuming clotting assay in the conventional protamine titration method with a rapid colorimetric assay. It offers the same accuracy in estimating the protamine dose as that of the conventional titration method, but allows the processing time to be shortened to within 5 min. In a similar manner, the colorimetric assay can also be employed with a heparin titration procedure to quickly assess the heparin dose required for protamine reversal. This would allow physicians to exercise a quick and accurate heparin back-titration to patients who are overdosed with protamine. PMID- 2597465 TI - In vivo performance of a transcutaneous energy transmission system with the Penn State motor driven ventricular assist device. AB - A transcutaneous energy transmission system (TETS) has been used to power the Penn State motor driven ventricular assist device in nine calf experiments, for a total of 316 days of cumulative in vivo experience. This is seen as an important step toward a completely implantable ventricular assist system and total artificial heart. The TETS converts an external 12 volt DC source via inductive coupling to a regulated 14 volt output voltage for use by the motor controller. A maximum output power of 70 watts is available. In calf experiments, the TETS output power averaged between 8 and 12 watts. The motor controller was not implanted in these experiments, awaiting further development of the miniaturized electronics. The TETS output was returned percutaneously to the external motor controller, allowing the TETS output to be monitored directly. System efficiency, from DC source to DC output, and including losses in 12 feet of cable, ranged from 55% to 70%, depending upon supply voltage, motor load, and degree of coil coupling. The subcutaneous coil was well tolerated, demonstrating only temporary, mild, superficial induration. PMID- 2597467 TI - The use of image processing in the investigation of artificial heart valve flow. AB - A circulation model enlarged ten times with a likewise enlarged model of the artificial heartvalve leads to a very slow motion of the fluid. Many methods of flow visualization can therefore be applied. The particle method has been chosen as the most appropriate for further processing. The flow is videotaped, two consecutive frames are selected and with the help of image processing the vector field, the streamlines and the velocity profiles are computed and drawn. PMID- 2597466 TI - Shear stress affects expression of major histocompatibility complex antigens on human endothelial cells. AB - Endothelialization of the inner face of a prosthesis appears to improve patency of small caliber arterial substitutes. The importance of understanding the factors that affect human endothelial cell behavior is highlighted by failure of vascular prosthetic grafts to endothelialize when implanted in man. In the present study, endothelial cells isolated from microvasculature are used for their ability to be easily selected from human adult fat, their proliferative capacity, and for their immunologic properties relevant to human pathology: allograft implantation, vessel injury or atherosclerosis. The system described provides a tool for assessing the individual roles of shear stress in modulating endothelial cell morphology and major histocompatibility complex (MHC) antigen expression. Using indirect immunofluorescent staining, initial results showed a homogenous increase of class I and appearance of class II expression after an exposure for 30 hr to physiologic arterial values. Significantly increased staining intensity was observed following exposure to supraphysiologic values. Moreover, precoating of substrate with fibronectin instead of poly-L-Lysine enhanced MHC straining intensity. Scanning electron microscopy (SEM) confirmed the activated morphology of stained cells. This provides a model to study involvement of MHC expression in endothelial cell activation under physical constraints. It may contribute to the development of biomaterial for implantation. PMID- 2597468 TI - In vitro and in vivo evaluation of a jellyfish valve for practical use. AB - A practical model (Model-1) of a jellyfish valve was developed, which was composed of a valve seat and a flexible membrane. The valve seat has 12 spokes to hold the membrane, and is made of solution-cast polyurethane coated with segmented polyurethane or Cardiothane. The flexible membrane is 200 microns thick, and made of segmented polyurethane or Cardiothane by a casting method. The valves were built into a sac type blood pump. In mock circulation tests, this jellyfish valve revealed performance superior to Bjork-Shiley (B-S) valves. No stagnation point was observed in the flow visualization study, and durability testing is ongoing beyond 7.5 months. The valves were used in animal artificial heart experiments for up to 112 days with good performance. No thrombi were formed on the valve membrane or around the spokes. Although a ring thrombus was observed behind the valve, it would be prevented by perfect adhesion of the valve seat to the blood pump. The plasma free hemoglobin level was less than 2 mg/dl during these experiments. These results suggest that a jellyfish valve (Model-1) is useful in ventricular assist devices, and in short-term bridge use of a total artificial heart. PMID- 2597469 TI - New polyurethane valves in new soft artificial hearts. AB - This article describes new bistable valves, and introduces a new soft heart that is easy to implant. Earlier, five polyurethane (PU) valves were implanted in the mitral position in sheep. All five survived for 1 year or more, and the valves, although calcified, were intact. Since the opening resistance was somewhat high, valves that are bistable were developed, which means they may be open or closed. These valves have lower opening resistance, and regurgitation is similar to that of mechanical valves. Eight calves have been implanted with a new, soft total artificial heart (TAH). Seven had bistable leaflet valves; the eighth had mechanical (Bicer) valves in the inflow position. Four of the calves were sacrificed after 22 to 43 days. At autopsy, the number of thromboemboli found, particularly in the kidneys, was low compared with previous experiments. None of these animals received anticoagulants other than the heparin given during heart/lung bypass. PMID- 2597470 TI - The Mitroflow pericardial valve. First five years of follow-up evaluation. AB - The first 5 years durability study on a substantial number of Mitroflow pericardial valves makes the substance of the present report. One hundred eighty eight valves were implanted on 166 patients before December 1985: 149 patients were discharged and are recalled annually. Follow up is 99% complete. In October 1988, mean follow up was 3.5 years (3-5.5). Total patients times years is 582. Sixty-two percent of the patients are asymptomatic, 58% in sinus rhythm. Forty seven percent do not receive any anticoagulant therapy. The linearized rates of thromboembolism (1.2% per patient-year) and endocarditis (0.17 per patient-yr) is minimal. Seven patients only had valve dysfunction requiring explantation (1.2% per patient-yr). At 5 years, freedom of structural deterioration is 95.2% +/- 2.1. Single cusp tear at a stent post is the most frequent lesion (86%) as calcifications are observed in three only (major in two, microscopical in one). Histology does not permit to ascertain whether the tear is due to tissue fatigue or abrasion. Moderate microscopic architectural disruption of the valvular tissue is observed. Composite indices of all valve mortality and morbidity show at 5 years a 89.7% +/- 2.9 freedom of events. These data, associated to the high mechanical and optimal clinical characteristics of the valve, published previously, confirm the satisfactory performances of the valve at 5 years. PMID- 2597471 TI - Inflammation as the possible cause of cystic radiolucencies in carpal bones of patients on hemodialysis. AB - In this investigation of the etiology of amyloid-associated arthropathy in hemodialysis (HD) patients, determination of whether amyloid deposition triggered the formation of the cystic radiolucent bone lesions was attempted. The relationship between these lesions in carpal bones and carpal tunnel syndrome (CTS) was studied by radiography and tomography, and one of the carpal bones, the os capitatum, was examined histologically at autopsy. The mean number of cystic radiolucent lesions in carpal bones of the 21 patients with CTS was significantly greater than that in the 43 patients without CTS. On tomograms, cystic radiolucent lesions of carpal bones had interconnections with joint spaces. Inflammatory fibrous granulation tissue, with or without amyloid deposits, was found in the cystic lesions. It was concluded that cystic radiolucent lesions in carpal bones of patients on HD was related to CTS, and that synovitis and subsequent chronic inflammation were responsible. Thus, amyloid deposits did not trigger the formation of such lesions. PMID- 2597472 TI - Effects of zeta potential on the permeability of dialysis membranes to inorganic phosphate. AB - Some patients on hemodialysis have elevated plasma phosphate values. The chemical and physical properties of dialysis membranes may cause reduced inorganic phosphate clearance, leading to hyperphosphatemia. The zeta potential was determined by a streaming potential method using an electrolytic, aqueous solution to elucidate discrepancies in phosphate ion transport through cellulosic and polymethylmethacrylate membranes. The authors also carried out dialysis experiments at 310K to obtain solute permeability for H32PO4(2-), overall mass transfer coefficient for HPO4(2-), and pure water permeability. This study demonstrates that permeability to inorganic phosphate ion does not vary with zeta potential for cellulosic membranes, but polymethylmethacrylate membranes with highly negative zeta potentials may suppress phosphate removal from patients on hemodialysis. PMID- 2597474 TI - Transcellular disequilibrium and intradialytic catabolism reduce the reliability of urea kinetic formulas. AB - To elucidate the limits of single-pool models as regard aberrations induced by urea transcompartmental disequilibrium during urea kinetics, mass balances and fractional clearances were studied, and original formulas developed to calculate urea clearance and distribution volume. In the early dialytic phases, aberrations were more evident, with low kinetic volume (VK) values and kinetic clearance (KK) values double those obtained by dialysate collection (KDC). Over the whole session, both VDC and VK were underestimated (9.9 and 8.2%), compared with anthropometric data (VA). In 3 patients, the comparison of VA and VDC, and the behavior of effective body water clearance (KE), agreed with the hypothesis of dialysis-induced catabolism. Both disequilibrium and hypercatabolism can affect the reliability of the single-pool urea kinetic model; because of overlap, their effects are difficult to separate, and became particularly important in high efficiency dialysis. A modified model, using V and CtET as input is suggested in order to establish the most appropriate dialysis prescription for uremia therapy. PMID- 2597473 TI - Calcium carbonate powder as a phosphate binder. AB - With increasing recognition of problems regarding the use of aluminum hydroxide as a phosphate binder, calcium carbonate has become the medication of choice. Use of calcium has, however, frequently been associated with development of hypercalcemia. At this institution, calcium carbonate powder as a phosphate binder, examination of its efficacy, and the frequency of hypercalcemia with its use were of great interest. Calcium carbonate powder (CalCarb-HD, 2.4 gms elemental calcium/packet) (CalCarb-HD, Lafayette Pharmacal Inc., Fort Worth, TX) was used in the study. Twenty-one end-stage renal disease (ESRD) patients (17 hemodialysis and 4 chronic ambulatory peritoneal dialysis) were chosen and converted from their previous binder (primarily, calcium carbonate tablets) to calcium powder. The dosage was adjusted to keep phosphorus levels at 3.5 to 5.5 mg/dl and calcium less than 11.5 mg/dl. At 2 months, the average calcium level in the 16 patients remaining in the study was 9.2 mg/dl, and the average phosphorus level was 5.2 mg/dl with an average calcium dose of 1.4 packets/day. By 7 months, the 8 patients remaining in the study had an average calcium level of 9.9 mg/dl with an average phosphorus level of 5.5 mg/dl; average calcium dose was 1.8 packets/day. Total episodes of hypercalcemia (calcium greater than 11.5 mg/dl) were two. Calcium carbonate powder appears to be an effective phosphate binder in the ESRD population. The relatively few episodes of hypercalcemia may be related to possible enhanced bioavailability of the compound secondary to its powdered form. PMID- 2597475 TI - Detection of bacteria in dialysate and its antibody in long-term hemodialysis patients. AB - The relationship between endotoxin, which was detected in the dialysate, and incidence of its antibody formation in long-term hemodialysis patients was studied. Bacteria in the dialysate were first obtained, identified, and cultured, and then endotoxin was obtained from the bacteria by extraction with phenol. Using the endotoxin obtained and Escherichia coli J-5 as the antigen, the endotoxin antibody was measured in the serum of long-term hemodialysis patients by enzyme-linked immunosorbant assay (ELISA). It was found that the percentage of endotoxin antibody-positive patients was significantly higher in hemodialysis patients when compared with healthy controls. It was also significantly higher in hemodialysis patients using synthetic polymer membrane dialyzers compared with those using cuprophan membrane dialyzers. These results suggest that endotoxin antibody detected in hemodialysis patients was derived from the dialysate, and that the dialysate must be kept bacteria free, especially in patients using high flux, highly permeable membrane dialyzers. PMID- 2597476 TI - Efficiency and biocompatibility of a polyethylene glycol grafted cellulosic membrane during hemodialysis. AB - Dialytic efficiency and biocompatibility of a new modified cellulose membrane (NMC) were examined in vitro and clinically. NMC was obtained by grafting polyethylene-glycol (PEG) chains to the membrane surface of ordinary cellulose (OC), and it was expected that the random movement of PEG chains would prevent blood cells and large plasma proteins from coming into contact with the membrane surface, resulting in improving the biocompatibility and thrombogenicity of the membrane. Surface characteristics of NMC were rendered anionic and hydrophilic, however, the activations of complement and platelet systems were clearly suppressed in NMC. Minimum heparin requirement for hemodialysis was significantly lower with NMC than with OC dialyzer. No significant difference in solute and water removal was observed between the two dialyzers. These results indicate that NMC can provide increased biocompatibility and antithrombogenic effect while retaining the essential dialysis efficiency of OC. PMID- 2597477 TI - Bedside formulas for K.t/V. A kinder, gentler approach to urea kinetic modeling. AB - Based on an empiric analysis of urea kinetic modeling equations, three formulas were derived for use at the bedside: (F1) Ob.t = 14.W.(K.t/V); (F2) target R = e K.t/V + 0.03 + UF/W; (F3) K.t/V = -In (R - 0.03 - UF/W); where Qb = blood flow (ml/min); t = session length (h); R = post/pre BUN; UF = ultrafiltrate volume (L/session); and W = postdialysis weight (kg). When a particular K.t/V is desired, F1 is used to estimate Qb for a given W and t. Qb, t, and/or dialyzer type are then adjusted until R = target R calculated by F2 (based on target K.t/V, UF, and W). F3 estimates delivered K.t/V from R, UF, and W. These formulas were validated against 336 conventional 3-point modeling sessions in 256 patients. The multiplier "14" in F1 actually averaged 12.5 +/- 2.8, the large standard deviation suggesting that use of F1 would often result in K.t/V values substantially above or below the target K.t/V. The main causes of error were unusual V/W or K/Qb. On the other hand, F2 and F3 were highly accurate: target R estimated by F2 predicted actual R (at a given K.t/V, UF, and W) very well (% error = 0.65 +/- 2.3); K.t/V estimated by F3 predicted actual K.t/V (% error = 0.74 +/- 2.7). The results suggest that attainment of a target R (F2) will ensure that the target K.t/V is being delivered; F3 is useful to estimate K.t/V.F1 is an initial estimate only of the dialysis Rx; it must be followed by adjustment of t, Qb, or dialyzer until target R (from F2) is attained. PMID- 2597478 TI - The effect of extracorporeal cholesterol removal on the progression of atherosclerosis. AB - High correlation of plasma lipid levels, especially low density lipoprotein (LDL) cholesterol levels, with the risk of coronary heart disease has been clearly indicated by epidemiologic studies. This study was undertaken to use an animal model of nondiet-induced hyperlipidemia in the homozygous Watanabe heritable hyperlipidemic rabbit (WHHL) to evaluate the effect of plasma cholesterol lowering on the progression of atherosclerosis, and to correlate plasma cholesterol levels with the amount of atherosclerotic plaque. Studies were carried out on ten homozygous WHHL rabbits divided into two groups: lipid lowering (treated) and control (nontreated). Lipid lowering was accomplished by thermofiltration (on-line plasma membrane filtration at 39 degrees C for removal of VLDL and LDL). The treated group had a significantly lower mean plasma level of total cholesterol over the course of the study than the nontreated group (293 vs. 655 mg/dl, p = 0.004). The amount of aortic atherosclerotic plaque in the treated group was also significantly lower than that in the control group (16.9 vs. 44.2%, p = 0.003). Microscopically, thickness measurements of the atherosclerotic lesions revealed that the control group had a thicker intima than the treated group. This study convincingly demonstrated the slowing or interdiction of progression of atherosclerotic lesions with lowering of the plasma total cholesterol level by thermofiltration. PMID- 2597479 TI - Improvement of peripheral circulation by low density lipoprotein adsorption. AB - Low density lipoprotein (LDL) was removed by repeated extracorporeal adsorption with a dextran sulphate cellulose column in 5 patients with clinical signs of poor peripheral circulation. The LDL apheresis was continued for 2 to 10 months, and symptoms such as cold or "heavy" legs, or intermittent claudication rapidly improved early in the treatment course in all 5 patients. Clearing of mentation occurred in 3, and recovery of kidney function was seen in 1 patient. These improvements occurred concomitant with a reduction in LDL level. PMID- 2597480 TI - A rabbit model for evaluation of an extracorporeal LDL removal system. AB - Elevated levels of plasma low density lipoprotein cholesterol (LDL) are associated with an increased incidence of atherosclerosis and its sequelae. A decrease in LDL levels correlates with a reduction in atherosclerosis. Drug therapy and diet have been moderately successful in lowering cholesterol levels, but require significant periods of treatment. Furthermore, a patient with genetically high LDL levels, as in familial hypercholesterolemia, may need a more rapid and reliable method of decreasing serum LDL. The present study was designed to test a device which can rapidly remove LDL from the circulation. The device consists of a filter cartridge filled with semipermeable hollow fibers which have a proprietary acidic polymer (pap) immobilized on the blood/plasma contacting surfaces; this polymer has been reported to selectively bind LDL cholesterol. The device was evaluated in a hypercholesterolemic rabbit model. Reductions in LDL serum concentration, ranging from 1.4-25.3%, occurred in 6/6 studies. All animals survived the procedure. Autopsy results at 10 days showed normal histology. Binding of other proteins (HDL, albumin) were minimal and no hemolysis was observed. Results of this preliminary study demonstrate the feasibility of reducing serum LDL levels with a hollow fiber device. PMID- 2597482 TI - Activation of neutrophil oxidative metabolism during cardiopulmonary bypass with membrane oxygenators. AB - Neutrophil oxidative metabolism was prospectively assessed in 9 consecutive patients undergoing cardiopulmonary bypass (CPB) with polypropylene hollow fiber oxygenators for open cardiac operations. Blood samples were collected at 10, 20, and 30 min of CPB. The generation of oxygen-free radicals by neutrophils was measured as luminol-enhanced chemiluminescence after stimulation with opsonized Zymosan and Phorbol Myristate Acetate. A significant increase in light emission was detected by using both the chemiluminescence stimulators. These data suggest that the contact of patient blood with foreign surfaces during cardiopulmonary bypass results in activation of phagocyte cells. PMID- 2597481 TI - Kinetics and quantitation of In-111 labeled platelet deposition on control and heparin-bonded polyurethane angio catheters in a dog model. AB - The dynamics of platelet deposition on control polyurethane catheters (CPC) and heparin-bonded polyurethane catheters (HBPC) were evaluated with In-111 labeled platelets (In-PLT) using a computerized gamma camera (CGC). Ten nonheparinized dogs (18-25 kg) had both femoral arteries catherized with 10 cm of CPC and HBPC (5 Fr.) 24 hr postinjection of 300-420 microcuries of In-PLT, and imaged for 3 hr with a gamma camera. Regional platelet deposition on three segments of catheters and the puncture site was determined. Catheters were harvested and radioactivity on the catheter segments (proximal: PROX, middle: MID, distal: DIST and puncture site: PS) of both was determined. From the platelet count in blood, and radioactivity in blood and segments of catheters, adjacent artery, and area of artery and catheter, the platelet-density [X10(3) (mean +/- S.D.)] on catheter and artery was calculated and tabulated. Proximal values were cath (CPC), 1289 +/ 1125; artery, 1355 +/- 587; cath (HBPC), 125 +/- 113; artery, 1149 +/- 1620. The middle values were cath (CPC), 1102 +/- 1109; artery, 1512 +/- 625; cath (HBPC), 132 +/- 108; artery, 1011 +/- 942. Distal values were cath (CPC), 780 +/- 584; artery, 132 +/- 108; cath (HBPC), 227 +/- 194; artery, 1457 +/- 1309. The puncture site values were cath (CPC), 106 +/- 382; artery, 1011 +/- 942; cath (HBPC), 164 +/- 135; artery, 1498 +/- 1240. The large standard deviation in retained platelets is due to embolization. The platelet-density and regional counts on catheter segments were lower with HBPC than CPC, as was the rate of platelet-deposition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2597483 TI - Characterization of blood microemboli associated with ex vivo left ventricular assist devices in a bovine model. AB - An ex vivo left ventricular assist device (LVAD) model was used in calves to study the production of blood microemboli (BME) and to evaluate possible correlations between constant-pressure filtration (CPF) measurements of flow resistant BME, light-scattering microemboli detection (LSMD), observable thrombus accumulation, and hematologic markers. Aortic LVAD cannulae were implanted through the chest wall in two calves, and each calf received a series of LVADs, each operating 1-4 days. Blood samples from the LVADs underwent CPF through 20 mu pore filters at 20 mm Hg to produce estimates of occlusive BME concentration. Laser (He-Ne) light was directed through the outflow cannula, and the differentially-scattered light was detected for computer estimation of microemboli size, volume, and frequency. Blood chemistry and coagulation parameters were also analyzed. Removed LVADs were examined with polar coordinate mapping of accumulated perivalvular thrombi. One ventricle produced significantly greater CPF results, LSMD results, and Factor XII levels. During the use of that ventricle, the CPF results increased slowly with time after LVAD connection, while the LSMD results and Factor XII levels increased immediately after connection, followed by a later decrease. This contrast is explainable in terms of the dynamic development of BME strength. The calf model appears useful for the study of thrombogenesis, and the CPF and LSMD methods of BME analysis complement each other, and other measurements. PMID- 2597484 TI - Dynamics of platelet adhesion to artificial materials and cultured endothelial cells under shear flow. AB - To evaluate the dynamic features of platelet adhesion to biomedical materials, a new shear flow testing apparatus was constructed. A cone-plate rotational viscometer, equipped with a transparent cone and transparent bottom window, was mounted on the stage of an inverted microscope. Test materials (glass, silicone, polyvinyl chloride, Thermanox, and porcine endothelial cells cultured on glass coverslips) were placed on the bottom window. Real time microscopic images of platelets adherent to the test materials in a shear rate range between 3.6 and 360 1/s were observed and recorded with a videocassette recorder. Time course changes in the number of adherent platelets were analyzed on the basis of a convective diffusion model. With respect to effective diffusivity of platelets (De) and the surface reactivity constant (K), less significant differences were found among artificial materials. In the case of cultured endothelial cells, both De and K, which were evaluated for the first time in the present study, were two to four orders of magnitude lower than those obtained with artificial materials. PMID- 2597485 TI - Immobilized albumin-immunoglobulin G for improved hemocompatibility of biopolymers. AB - Efforts to render blood contacting surfaces less thrombogenic have included chemical modification of the polymer, as well as surface modifications with proteins, anticoagulants, or antiplatelet agents. Studies reported from this laboratory in the past have shown that certain surfaces pretreated with albumin Immunoglobulin G (alb-IgG) become relatively more hemocompatible (reduced platelet adhesion, minimal thrombus). However, absorbed proteins, including alb IgG, desorb rapidly when exposed to circulating blood. Therefore, efforts were made to immobilize alb-IgG on glass or Biomer as follows: a 2 mg/ml solution of IgG was crosslinked with glutaraldehyde on the test surface. Crosslinked IgG was then treated with mercaptoethanol to reduce the disulfide bonds, followed by incubation with albumin previously reduced with mercaptoethanol under conditions that allowed reassociation of disulfide bridges between albumin and crosslinked IgG. Alb-IgG immobilized at the test surface following this method was found to remain at the interface when the surface was exposed to blood in vitro for up to 7 days under static conditions. Glass or Biomer surfaces with crosslinked Alb-IgG showed considerable reduction in the adhesion of 111In-platelets and adsorption of 125I-fibrinogen when test surfaces were analyzed in a flow chamber. Under identical experimental conditions, surfaces with crosslinked albumin alone were not effective in reducing the adhesion of platelets. Crosslinked IgG or immobilization of IgG on crosslinked albumin following the above methods rendered the surfaces more thrombogenic. It was noted, however, that crosslinked proteins on Biomer were dislodged rapidly in areas with turbulent flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2597486 TI - Long-term results of a new antithrombogenic cardiac wall substitute. AB - We evaluated the long-term results of a new antithrombogenic cardiac wall substitute which is composed of collagen-coated ultrafine polyester mesh cross linked by a hydrophilic polyepoxy compound (CUFP), and compared it with glutaraldehyde-treated equine pericardium (GA graft). In an animal study, 20 CUFPs and 18 GA control grafts were implanted as patches in the right ventricular outflow tract in 38 dogs. In the CUFP at 28 days after implantation, a thin neointima, which was almost endothelialized, had been formed. Fibroblasts and vasa vasorum were seen inside both the neointima and the graft wall. At 168 days, transmission electron microscopy revealed smooth muscle-like cells in the neointima, with endothelialization. The CUFP at 486 days had maintained a white, shiny, smooth, thin, and uniform neointima with endothelialization. Neither ulcer nor thrombus formation was seen on the surface, while in the GA graft at 353 days, no endothelialization was noticed in the center and almost no fibroblasts had infiltrated into the graft wall. From these results, the CUFP should be an ideal candidate for cardiac wall substitution. PMID- 2597487 TI - Influences of ventricular assist device pumping on blood coagulation. AB - A left ventricular assist device (VAD) with a smooth surface of segmented polyurethane was implanted in five goats for 10-55 days, and plasma levels of fibrinogen (Fg), prekallikrein (PK), fibrinogen, fibrin degradation products (FDP), antithrombin III (AT III), prothrombin time (PT), partial thromboplastin time (PTT), platelet (Pl) count, and platelet aggregation (PlAg) induced by adenosine diphosphate were measured during the experiment. Heparin was administered during surgery and no systemic antithrombotic therapy was given thereafter. Before the third postoperative day (POD), plasma levels of Fg and PK were at their lowest, and increased afterward. Between the second and fifth POD PT and PTT increased to 130-160%, and returned to normal gradually. Plasma FDP appeared on the second POD and reached peak values of 10-40 micrograms/ml on the sixth POD. Platelet and AT III levels showed no uniform tendency, but the rate of PlAg decreased to levels of 6-77% before the fifth POD and remained low at approximately 80%, influenced by the pumping even after the 25th POD. In summary, VADs themselves activated coagulation and induced consumption coagulopathy to some degree. However, most of the parameters returned to normal within 2 weeks. PMID- 2597488 TI - A biolized implantable ventricular assist device compatible with IABP console. AB - A low pressure pneumatic pusher plate blood pump was developed for temporary right, left, or biventricular assist. Important features of this pump are its 1) driveability by the standard, easily available intraaortic balloon pump (IABP) console; 2) gelatin coated internal surface for blood compatibility; 3) essentially flat disc shape, 3 cm thick and 11 cm in diameter, for optimal anatomic fit; and 4) unique pusher plate guide mechanism to ensure linear motion without deflections of the diaphragm, and consequent uniform flow distribution into the pump. The guide telescopes into itself to avoid a housing protrusion for easy implantability; this controlled movement also provides a number of performance, control, and diagnostic benefits. The pump's 60 ml displacement gives up to 4.7 L/min at 80 bpm and 6.7 L/min at 120 bpm outputs in a mock loop. This VAD has been implanted in two calves for 43 to 84 days, continuously driven by a Datascope IABP console. An average 5 L/min pump output has been observed in both synchronous and fixed rate modes. No anticoagulation was required. We expect extensive clinical use of this VAD, based on its reliability, low cost, and simplicity. PMID- 2597489 TI - Chronic ovine evaluation of a totally implantable electrical left ventricular assist system. AB - The totally implantable Novacor left ventricular assist system (LVAS) comprises a pump/drive unit (VAD), electronic control and power subsystem (ECP), variable volume compensator (VVC), and belt skin transformer (BST). The system is now undergoing chronic in vivo evaluation. Cumulative animal testing of VAD, VVC, and BST subsystems are 12.1, 4.9, and 43 years, respectively. The longest implants were 279 days for the VAD, 767 days for the VVC, and 1,148 days for the BST. A chronic implant of the total system was electively terminated at 260 days. The LVAS was powered via the BST. Continuously monitored hemodynamic and pump parameters have demonstrated normal hemodynamics and LVAS operation. Periodic VVC determinations suggest a 0.8 ml/day diffusive gas loss. Tether-free operation has been demonstrated with an Ag-Zn battery backpack. The animal was healthy and free of infection as indicated by routine hematologic, biochemical and serum enzyme determinations. Hemolysis is minimal (plasma free hemoglobin less than 5 mg%). Pump output ranged from 7 to 8 L/min. Severe valve calcification was the reason for elective termination at 260 days. This preclinical in vivo experience, and in vitro reliability studies, demonstrate efficacy of the total system. PMID- 2597490 TI - A new implantable burst generator for skeletal muscle powered aortic counterpulsation. AB - Skeletal muscle (SM) can be used for long-term circulatory assist. To generate contractions of appropriate duration and strength, SM requires bursts of electrical pulse trains. Presently, the implantable pulse train stimulator for SM assist is unable, at different heart rates, to adjust pulse burst duration or delay time, adversely affecting timing of counterpulsation. A prototype implantable microprocessor based stimulator (Medtronic Prometheus) has been developed to address this issue. The purpose of this study was to test this generator in an acute dog model. A dual chambered counterpulsation device was connected to the aorta in six dogs, using the latissimus dorsi to power the pump. The generator was connected by sensing/stimulating leads to the heart/left thoracodorsal nerve, programmed to give bursts of 2 V, 30 Hz, and pulse widths of 180 microsecs. Burst delay and duration was set as a fixed percent of the R-R interval of the EKG. The baseline aortic pressures ranged from 75/33 to 118/87 mmHg. During counterpulsation, diastolic pressure increased from 17 to 50 mmHg (30-111% increase). With changing heart rates, the pulse generator spontaneously readjusted its burst delay and duration, maintaining optimal diastolic counterpulsation without systolic interference. We conclude that this new pulse generator can stimulate SM for counterpulsation at varying heart rates, and is suitable for implantation in chronic studies. PMID- 2597491 TI - Muscle powered circulatory assist device for diastolic counterpulsator. AB - A diastolic counterpulsator that uses either skeletal muscle or pneumatic actuation was developed. The unit is positioned between the latissimus dorsi and the chest wall, without interference with collateral blood supply, and is connected in series with the descending aorta. The system was able to generate stroke volumes between 52 and 16 ccs against pressures of 60 and 140 mmHg, respectively. Stroke work at 200 msec stimulation averaged 2.8 X 10(6) ergs. Power output at an afterload of 100 mmHg, and at a rate of 60 bpm, was 0.51 W. Back-up pneumatic actuation provided by an intraaortic balloon pump resulted in a 46% increase in the endocardial viability ratio (EVR). PMID- 2597492 TI - Follow-up of reverse dextrose clearances in patients undergoing CAPD. AB - Three hundred eighty-eight sequential reverse dextrose clearances (RDC) have been performed in 61 unselected patients (12 of whom were diabetics), whose mean age was 54 years (30-79). They were treated for a mean time of 23 +/- 12 months (0 60); the total observation time was 1,440 months. One hundred forty-two episodes of peritonitis were registered, producing a peritonitis incidence of 1 episode per 10.2 patient months. The RDC values are significantly inversely related to dwell-time and show a tendency to increase over time; they never, however, reach statistical significance. Age of patients, episodes of peritonitis and primary renal disease (diabetes) had no influence. It is important to underline the significant inverse relationship between ultrafiltration and residual diuresis. Unknown mechanisms regulate this relationship. PMID- 2597493 TI - Intraperitoneal therapy with interferon-alpha in CAPD patients with relapsing bacterial peritonitis. AB - In CAPD patients with relapsing bacterial peritonitis who do not benefit from intraperitoneal therapy with IgG (IgG nonresponders), the authors demonstrated that peritoneal macrophages are deficient in IgG Fc receptors (FcR) and, therefore, unable to kill bacteria, independent of the levels of the opsonic molecule IgG in the peritoneal dialysis effluent (PDE). Because previous studies showed that interferon-alpha (IFN-alpha) is able to increase in vitro the number of PM0 IgG FcR in CAPD patients with relapsing bacterial peritonitis, the authors studied the in vivo effects of IP administration of IFN-alpha (1,000 IU daily in the overnight exchange for 12 months) on: PM0 superoxide generation; PM0 bacterial killing; PM0 IgG FcR; the number of bacteria in the PM0 cytoplasm; and peritonitis relapses in these patients. By the 10th day, IFN-alpha induced a progressive rise in all of the previously depressed PM0 functions tested, the disappearance of bacteria from the PM0 cytoplasm, and no further episodes of bacterial peritonitis were detected during 12 months. These data indicate that IFN-alpha may represent a useful tool for preventing infections in CAPD patients with relapsing bacterial peritonitis. PMID- 2597494 TI - Effect of varying dialysate bicarbonate concentration on serum phosphate. AB - Hyperphosphatemia is practically a universal problem in patients with chronic renal failure. Conventional treatment of hyperphosphatemia in this situation is either only partially effective or may be associated with potentially serious adverse effects. The authors examined the effect of inducing a metabolic alkalosis on serum phosphate in chronic hemodialysis patients by increasing the concentration of bicarbonate in dialysate. Seven patients participated in the study. Each patient was on dialysis for 2 weeks with each of 2 dialysate regimens. Regimen A contained a bicarbonate concentration of 25 mEq/L and Regimen B a bicarbonate concentration of 40 mEq/L. Despite Regimen B resulting in a significant increase in predialysis and postdialysis serum bicarbonate concentration and arterial pH, no significant difference in serum phosphate was demonstrated after 2 weeks of therapy. PMID- 2597495 TI - Significance of various anticoagulation therapies during use of a left ventricular assist device. AB - A multicomparative study to establish adequate anticoagulation therapy for left ventricular assist devices was undertaken by administrating various anticoagulants: heparin, a prostacyclin analogue combined with a protease inhibitor; thromboxane A2 synthetase inhibitor; or a protease inhibitor alone. Our investigation suggested that combined administration of prostacyclin analogue and protease inhibitor (FUT-175) is ideal anticoagulation therapy from the point of blood coagulation and fibrinolysis. Currently, however, sole administration of FUT-175 is adequate anticoagulation therapy during clinical use of left ventricular assist devices. PMID- 2597497 TI - In vitro and in vivo performance evaluation of a totally implantable electrohydraulic left ventricular assist system. AB - The biolized electrohydraulic left ventricle assist devices were tested in 14 calves with an average survival time of 162 days and as long as 250 days without the use of anticoagulants. In vitro, the system pumped 4.1 L/min at a low 4.8 mmHg fill pressure with a mean afterload of 100 mmHg and rate of 46 bpm. A flow rate of 13.5 L/min was observed at 155 bpm and 110 mmHg afterload. Motor frequency and current increased with increasing flow rate (162 Hz, 0.67 amp at 2.5 L/min; 484 Hz, 2.43 amp at 13.5 L/min). Flow rate did not change significantly with afterload pressure. The complete system was implanted in a 100 kg calf. Synchronization of the blood pump with the natural heart was demonstrated at heart rates of 85 to 167 bpm. The synchronized flow rate varied from 6 to 10.5 L/min despite the considerable heart rate changes and stroke variations. The system hemodynamic performances were acceptable and met NIH requirements. PMID- 2597496 TI - Mean flow velocity patterns within a ventricular assist device. AB - A laser Doppler anemometry system was used to measure fluid velocities at 127 locations within a plexiglas model of the 70 cm3 Penn State electric ventricular assist device (VAD) fitted with Bjork-Shiley convexo-concave tilting disk valves. The velocity measurements were made using a seeded blood analog fluid that matched the kinematic viscosity of blood and the refractive index of plexiglas. At each location, 250 instantaneous velocity realizations were collected at eight instances during the pump cycle. The data were filtered and averaged to calculate mean (ensemble averaged) velocities. The results indicate that the largest mean velocities are created during systole in the VADs outlet tract, and during diastole in the major orifice of the mitral valve. A single vortex centered roughly about the axis of the cylindrical portion of the pump is created during early diastole. This vortex, which persists into early systole, provides good washing of the VAD walls. However, it does appear to impede the flow entering the VAD through the minor orifice of the mitral valve. High velocities also occur during diastole along the minor orifice wall of the outlet tract and are directed into the chamber. These retrograde velocities suggest the presence of a regurgitant jet near the wall of the prosthetic valve. PMID- 2597498 TI - Pressure indices of myocardial oxygen consumption during pulsatile ventricular assistance. AB - Left ventricular (LVP) and intramyocardial (IMP) pressure indices were compared with left ventricular myocardial oxygen consumption (MVO2) during pulsatile ventricular assistance to determine if MVO2 can be predicted under conditions of ventricular support. During five acute anesthetized calf experiments, IMP and LVP were recorded for control and six conditions of support. The assisted conditions were asynchronous and synchronous, 1:1 or 1:2; each control mode with atrial uptake only or combined atrial and ventricular uptake. IMP was measured by implantation of a miniature pressure transducer in the midanteriolateral wall of the left ventricle. MVO2 was determined using the radioactive microsphere blood flow technique and blood gas data. Mean values of peak systolic pressure, maximum dP/dt, and integral of Pdt were calculated for IMP and LVP for each condition. Pressure indicators of left ventricular function were found to correlate well with MVO2 during conditions of pulsatile support. PMID- 2597499 TI - Computer model of ventricular interaction during left ventricular circulatory support. AB - The authors used a computer model of the heart and circulation to test the hypothesis that anatomic ventricular interactions are responsible for the observed instances of right ventricular failure during use of a left ventricular assist device. The model predicts that left ventricular pressure-unloading with a LVAD, in the presence of isolated systolic interaction, results in impairment of RV function, whereas with isolated diastolic interaction, RV function is improved. Due to competition between these two interactions, there is a negligible overall effect of ventricular anatomic interactions in determining right ventricular function in the normal heart. PMID- 2597500 TI - An original inflow cannula for paracorporeal assist devices. AB - Cannulae for paracorporeal ventricular assist devices have been clinically shown to be limiting factors in optimal circulatory support. A new inflow cannula has been manufactured according to an original silicone rubber molding process, permitting a hemocompatible inner surface. The cannula is 200 mm in length, with a 10 mm internal diameter. The wall is 3 mm thick and reinforced by a stainless steel spiral spring embedded in the silicone. An external ring permits adequate interface between the cannula and the endocardial surface of the atrium. A compliant external segment on the inflow cannula, free of any spiral spring, allows adjustment of vacuum to optimal values, thus avoiding inflow obstruction. The cannula has been tested during 1 to 5 days of left ventricular bypass in calves (n = 15). A Symbion AVAD, Utah 85 VAD, or Centrimed pumps were used. Adequate heparinization was maintained throughout. Paracorporeal flow was 0.045 L min-1 kg-1. In vivo evaluation was made by hemodynamic studies and the incidence of thromboembolism. The cardiac cavities, cannulae, and peripheral vessels were carefully searched for thrombi and emboli at autopsy. The atrium, the interface between atrium and silicone cannula, and the cannula itself were found free of any deposit. This aspect differed from that observed previously with available PU or PVC cannulae. PMID- 2597501 TI - Regulation of coronary circulation during left ventricular assist. AB - Regulatory mechanisms of coronary circulation during left ventricular assist (LVA) were studied in chronic experiments using adult goats. In normal heart studies (n = 3), circumflex coronary artery flow (CxF) and endocardial blood flow (MBF) decreased in proportion to decrease of tension time index (TTI). Mean CxF/TTI was constant at 0.22, whether the LVA functioned or not. In the left anterior descending branch ligation model (AMI) study (n = 2), CxF decreased according to decrease of TTI throughout the experiment, if the bypass ratio was kept within a normal range of systemic pressure. Mean CxF/TTI was maintained at approximately 0.21 by LVA, fell to 0.16 when LVA was turned off during the early stages. Coronary circulation during LVA was regulated by oxygen demand if systemic circulation was maintained, and LVA improved oxygen demand-supply balance in failing hearts. PMID- 2597502 TI - An electrohydraulic ventricular assist system with a linear actuator. AB - An electrohydraulic ventricular assist system with a linear actuator was developed, and in vitro and in vivo evaluations were performed. During in vitro evaluations this system could yield 5.6 L/min of pump flow against a mean afterload of 100 mmHg. Durability tests were performed for more than 4 months. The system was implanted in three goats and a maximum pump flow of 4.2 L/min was obtained against a mean afterload of 100 mmHg, and 3.2 L/min against 130 mmHg. These evaluations have proven that the system can maintain stable hemodynamics under various conditions. PMID- 2597503 TI - A new method of assessing left ventricular function under assisted circulation using a conductance catheter. AB - A new method of assessing left ventricular (LV) systolic function without terminating assisted circulation (AC) was investigated using a LV volume catheter (conductance catheter) in canine cardiopulmonary bypass (CPB) (Group 1, n = 7) and left heart bypass (LHB) (Group 2, n = 5) models. The hearts were subjected to either 20 min of global ischemia (IS), with a subsequent 80 min of reperfusion under CPB, or regional IS under LHB. Instantaneous LV pressure-volume data acquisitions were repeated during transient (15 sec) acute volume loading without terminating bypass. The relationship between the stroke work (SW), determined as the area of the pressure-volume loop, and the end-diastolic volume (EDV), were highly linear at every study point (mean: r = 0.956-0.986 in Group 1, r = 0.974 0.987 in Group 2). The slopes of SW and EDV (preload recruitable stroke work: PRSW) significantly decreased after IS, in both Group 1 and Group 2. In conclusion, measurement of PRSW without terminating bypass seemed to be useful in evaluating LV systolic function in patients under AC. PMID- 2597504 TI - An ambulatory, intermediate term left ventricular assist device. AB - A portable, percutaneous, battery-operated left ventricular assist device intended for intermediate and long-term use is described. The system performed satisfactorily in vitro for periods of up to 9 months and in vivo for periods in excess of 3 months. Long-standing hypertension was observed in a 98 day implant with accompanying renal and visceral vascular changes. No evidence of peripheral thromboembolism was seen. Examination of the textured blood pump surface revealed an established biologic lining, characteristic of that previously seen in calves with some evidence of peripheral calcification. PMID- 2597505 TI - Sustained heart failure induced by repeated microsphere injections for left ventricular assist device testing. AB - A subacute to chronic heart failure model was established to test left ventricular assist device (LVAD) systems. Five calves were anesthetized and instrumented. Heart failure was induced by daily injection of polystyrene microspheres (37-70 microns) into a left coronary catheter. The last three animals had an atrio-aortic pulsatile LVAD implanted. Cardiac output (CO) decreased from 12 to 5.5 L/min, and SV from 120 to 60 ml, whereas left atrial pressure (LAP) increased from 12 to 25 mmHg within 10 to 20 days in the two animals without LVAD support. Both animals stopped eating and drinking. The LVAD experiments were terminated after 5, 10, and 11 days. Cardiac function was determined during daily pump-off tests. After repeated microsphere injections, LAP increased to 30 and 50 mmHg, and CO decreased to 4 and 6 L/min without pump support. Daily stepwise microsphere injections induce a sclerotic cardiomyopathy in a safe and reliable manner. PMID- 2597506 TI - Study of heat dissipation to the lung from a thermal ventricular assist system. AB - The thermally powered left ventricular assist system (LVAS) requires that heat be dissipated to surrounding lung tissue and blood. This acute study was conducted in three anesthetized calves (weighing 84.3 +/- 14.3 kg) to evaluate the mechanisms involved in the dissipation of heat to the lung tissue. The heaters were placed in contact with the left lung surface and skeletal muscle tissue. Compared to the muscle tissue, heat flux to the lung was approximately three times higher for the same surface temperatures. For a constant heat flux, lung interface temperature tended to vary inversely with the cardiac output and ventilatory flow. This preliminary study demonstrated that the level of heat generated by the thermal LVAS can be effectively dissipated to the lung, with the convection mechanisms of airflow and blood flow playing a major role. PMID- 2597507 TI - Myocardial oxygen consumption. Comparison between left atrial pulsatile synchronous and asynchronous bypass. AB - This controlled study was undertaken to quantitate the effect of R-wave synchronization (counterpulsation) on myocardial oxygen consumption (MVO2) as reflected by the tension time index (TTI) during pulsatile left atrial to aortic bypass. Pulsatile ventricular assist devices were implanted in eight anesthetized, fully hemodynamically instrumented animals. After baseline measurement of TTI, heart rate, cardiac output, mean aortic and left atrial pressures, pulsatile left atrial to aortic bypass was instituted. Measurements were then continuously recorded during both left atrial pulsatile synchronous (LAPS) and asynchronous (LAPAS) bypass periods of pumping. Heart rate and mean aortic pressure were controlled throughout the experiment. TTI = 1819 +/- 95 mmHg sec (control); 987 +/- 127 mmHg-sec (LAPAS); and 763 +/- 89 mmHg-sec (LAPS). The results indicate TTI, and therefore MVO2, is reduced significantly from control levels by either LAPS or LAPAS bypass. However, R-wave synchronization (counterpulsation) offers no further benefit in reducing TTI over the less complex LAPAS or full-to-empty mode pumping. PMID- 2597509 TI - A unique left-right flow imbalance compensation scheme for an implantable total artificial heart. AB - A new method has been developed for accommodating the difference between pulmonary and arterial flows in a totally implantable, hydraulically actuated total artificial heart (TAH). The left and right sides are alternately pumped, with concurrent filling of one pump and ejection from the other. A small hydraulic fluid chamber is used to compensate for the higher left sided flow. This chamber is incorporated into the left inflow of the TAH, with the flexing bladder in contact with atrial blood, and the hydraulic fluid communicates with the right sided hydraulic chamber. The volume of hydraulic fluid that enters and exits the latter chamber constitutes a corresponding reduction in the right sided blood chamber stroke volume. Placement of this compensation chamber in the left side inflow provides a negative feedback of the right sided flow, based on the left atrial pressure (LAP). Higher LAP (indicating too much right sided flow) leads to higher fluid flow to and from the compensation chamber and a lower right sided blood flow and vice versa. The hydraulic flow resistance can be preadjusted to yield a 15% flow difference at an LAP of 15 mmHg. PMID- 2597508 TI - Comparison of direct mechanical ventricular actuation and cardiopulmonary bypass. AB - Direct mechanical ventricular actuation (DMVA) is a non-blood-contacting method for biventricular support. To compare effects of DMVA and cardiopulmonary bypass (CPB), 13 swine were supported by DMVA or CPB during 4 hours of ventricular fibrillation. Hearts were then rapidly excised and sectioned into right ventricular (RV) and left ventricular (LV) free wall slabs and subjected to total normothermic ischemia. Time to peak ischemic contracture (TIC) of LV endocardium (endo), LV epicardium (epi) and RV were determined using Millar needle transducers. Mean TIC was compared between DMVA (n = 6), CPB (n = 7), and control (n = 18). Significant decreases in LV endo TIC were found after DMVA (53.3 +/- 3.3 min) and CPB (56.2 +/- 2.4 min) compared with control (62.5 +/- 1.0), p less than 0.05. Myocardial blood flow was measured using microspheres during normal sinus rhythm and after 2 and 4 hr of circulatory support. Nonsignificant decreases in endo flow occurred during CPB and DMVA compared with control. LV endo adenosine triphosphate (ATP) levels (mumol/g dry weight) were significantly decreased after DMVA (9.0 +/- 2.5) and CPB (4.0 +/- 2.7) compared with control (17.8 +/- 0.6), p less than 0.05. Although CPB maintained mean arterial pressure by increased pump flows (mean, 129 ml/kg/min) and LV intracavitary pressures were kept below 5 mmHg with LV venting, resulting endo flows and ATP levels were decreased. DMVA generated decreased cardiac outputs (mean, 67 ml/kg/min) under these vasodilated states, yet maintained endo flow and ATP levels as well as CPB. These experimental data show that different mechanisms of myocardial perfusion and metabolism result from CPB and DMVA. PMID- 2597511 TI - Experience with an emergency resuscitation system. AB - The need for a portable extracorporeal support system that can be rapidly initiated for various types of cardiopulmonary failure is well known. The authors report on a system consisting of 3/8 inch tubing, a Sci-Med membrane oxygenator, Omnitherm heat exchanger, Biomedicus or Sarns centrifugal pump, portable battery, and oxygen tanks. The system is mounted on a cart for easy mobility and can be primed in 5-10 min. USCI, DLP, or Axiom cannulas can be inserted femorally. Over 30 months, 29 patients, aged 19-78 years, underwent extracorporeal membrane oxygenation (ECMO) support for cardiac arrest during catheterization (10 patients), shock secondary to acute myocardial infarction (MI) (10 patients), elective percutaneous transluminal coronary angioplasty (PTCA) support (four patients), postcardiotomy failure (four patients), and exposure hypothermia (one patient). Adequate support was achieved in all but one patient. Device flows ranged from 0.2 to 6.0 l/min. There were six survivors (elective PTCA support, three patients; cardiac arrest during catheterization, three patients). Complications included bleeding (15 patients), deep venous thrombosis (three patients), and pump failure (one patient). A portable ECMO system has been developed that allows rapid institution of circulatory support. PMID- 2597510 TI - The spindle pump. Development of a nonpulsatile blood pump for assisted circulation. AB - The spindle pump is a combined working nonpulsatile blood pump, i.e., a centrifugally propelling device. This special concept was chosen to tackle the main problems of nonpulsatile pumps, such as thromboembolic complications, sealing difficulties, and traumatic hemolysis. The first two of these problems were relatively simple to solve compared with the third problem--traumatic hemolysis. Various modifications and constructive steps of the spindle pump were necessary to keep stress on blood components within adequate limits. The actual prototype--tested in three acute experiments and eight experiments with a longer pumping duration (the longest lasting 63 hours)--is described in extenso, and its development is discussed. PMID- 2597512 TI - Methods for volume assessment of an air filled compliance chamber. AB - The air-filled (120 ml) compliance chamber employs a Dacron covered Hexsyn-butyl bilaminar diaphragm to minimize gas diffusion. Finite permeability dictates the need for a means to detect the remaining air volume and a refill port for gas addition. X-ray studies were used to detect radiopaque chamber markers in cadavers. Tangential X-ray cinematography enabled detection of chamber volumes less than 100 ml and diaphragm center deflection predicted volume to within +/- 6 ml of the actual volume. An electrically driven left ventricular assist pump (90 cc) was used to evaluate motor current (MC) and intracompliance pressure (IP) as indicators of low compliance volume. Peak MC was a function of both hemodynamic output power and compliance volume. Thus, if the peak current for a given hemodynamic output is known, variances may be indicative of low compliance volumes. The cyclic minimum IP vs. volume was +1, -3, and -13 mmHg for compliance volumes of 120, 90, and 80 cc, respectively. Ejection velocity did not significantly affect IP. In conclusion, X-ray studies and MC are useful as noninvasive means of assessing the need for compliance refill. IP, though measured invasively, is the most sensitive volume-dependent parameter. PMID- 2597513 TI - Fine control of reinnervated muscle. Dynamic rehabilitation of facial paralysis. AB - Satisfactory rehabilitation of the paralyzed face has yet to be achieved. Ideally, both mobility and symmetry should be restored. In five rabbits, motion signals were picked up from the intact side by miniature strain gauges and channeled by means of an electronic circuit to electrodes placed around nerve pedicles previously implanted into the paralyzed side. An analog current produced in response to muscular contraction (afferent limb) resulted in graded and sustained contraction of the reinnervated side (efferent limb). In six animals, the tension of reinnervated strap muscles could be adjusted by varying the pulse width (0.1-10 msec) of a constant (0.5 mA) current applied to the nerve pedicles. Contraction (strain-gauge compression) of the intact face was followed by reciprocal graded relaxation of the reinnervated straps. Conversely, facial relaxation (elongation) induced graded strap contraction. An agonist-antagonist relationship was, thus, created between the two effectors. This approach may allow the paralyzed face to be electrically reanimated from the intact side in a symmetrical fashion closer to the physiologic state. PMID- 2597514 TI - A canine model for global control of the reimplanted larynx. A potential avenue for human laryngeal transplantation. AB - Previous attempts at laryngeal transplantation have failed because the grafted organ could not be dynamically rehabilitated. Nerve-muscle pedicles were used to reinnervate each of the principal intrinsic laryngeal muscles in 20 dogs after autotransplantation with conservation of the essential nutrient vessels. Afferent information obtained by sensors fixed to the chest (a strain gauge and transthoracic impedance electrode) was channeled to an electronic package for coordinated stimulation of pedicles reinnervating the posterior cricoartenoideus (opening), the cricothyroideus (elongation) and the thyroarytenoideus (closure of the vocal cords) by perineural electrodes. Corresponding vocal cord motion was videotaped on the same screen as sensor displacements and stimulating currents (approximately 2 V, 60 Hz, and 4 msec pulse width). Clear responses were recorded in all evaluable animals (n = 8), but contraction was stronger with longer reinnervation time (3-7 weeks). Based on this feasibility study, chronic experiments are planned that will set the ground work for possible future human laryngeal transplantation. PMID- 2597515 TI - Technology and long-term application of an epineural electrode. AB - An epineural electrode (ENE) was developed to achieve a controllable, progressive muscle contraction and reduce muscle fatigue during functional electrostimulation. In vitro studies of annular (torus-shaped) electrodes have been carried out to select adequate electrode materials and electrode diameters. We investigated the long-term stability of ENEs using different intensities of current (range: 0.8-1.2 mA) in sheep and rat experiments. Depending upon size and material, ENE tolerates anodic and cathodic impulses of up to 1 msec and 8 mA (peak current). ENEs were used during clinical application in four paraplegic patients (16 channel implants) for stimulation of lower extremities, and in nine quadruplegic patients (eight channel implants) for diaphragm pacing, for a total observation time of 37 patient years. The low rate of clinical complications, including no corrosion of the electrodes or significant loss of nerve fibers, seems related to the small dimensions of the electrode (less than 1 mm2). PMID- 2597516 TI - Comparative in vitro encrustation studies of biomaterials in human urine. AB - A new dynamic in vitro human urine model was developed to compare biomaterial encrustation. The model incorporates a capacity to study seven biomaterials, a daily urine inflow of 500 ml, a reservoir capacity of 700 ml, and a turnover rate of four days. Encrustation studies performed for 2 weeks in sterile and infected (Proteus Vulgaris) urine on segmented polyether polyurethane, polyester polyurethane, silicone (Mitsui), silicone (Dow Corning), biothane, biolor 1 and biolor 11 demonstrated that biolor 11 (silicone-carbon composite) caused the least encrustation. Encrustation analysis showed brushite in the sterile model and struvite and ammonium acid urate in the infected mode I. Biolor II should have beneficial applications in catheters, stents and prosthetics which come in contact with urine. PMID- 2597517 TI - Modeling urea kinetics with two vs. three BUN measurements. A critical comparison. AB - Hemodialysis urea modeling usually requires three BUN measurements, C1, C2, and C3 (3-BUN), to determine urea generation rate (G) and volume of urea distribution (V) from dVC/dt = f(C, V, G). We eliminated the requirement for C3 by modifying the algorithm to generate a periodic solution to the equations describing C1 and C2 (2-BUN). During 156 consecutive dialyses in 37 patients there were no differences in V or G by the two methods: V = 38.3 +/- 1.3 L, G = 6.35 +/- 0.22 mg/min (2-BUN); V = 37.9 +/- 1.3 L, G = 6.08 +/- 0.23 mg/min (3-BUN). Theoretic analysis showed that transient departure from a constant protein intake produces greater errors in average G determined by the 3-BUN model than by the 2-BUN model. We compared predicted predialysis BUN values to measured predialysis BUN (mg/dl) at two days, one week and two months following the modeled dialysis. The 2-BUN method accurately predicted C3 in 156 studies: r = 0.90, mean error 6.8 +/- 6.0% (SD). Prediction of predialysis BUN at one week was less accurate for both methods: mean error 10.4 +/- 7.1% (2-BUN), 16.0 +/- 10.7% (3-BUN). At 2 months, the correlation between measured and calculated predialysis BUN fell to 0.59 (2 BUN) and 0.65 (3-BUN). Deviations from predicted BUN increased with time regardless of the model; no clear advantage of either method was seen at longer time intervals. Computer CPU time required to calculate V and G remained under 1 sec for the 2-BUN method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2597518 TI - Limitations of short dialysis are the indications for ultrashort daily auto dialysis. AB - Dialysis efficiency can be increased while shortening the duration of the treatment by the use of highly permeable dialysis membranes, larger surfaces, and higher blood and dialysate flows. However, vascular repletion of water and solutes, compared with the amount removed by rapid dialysis, is a limitation of short dialysis. This can be overcome by ultrashort daily dialyses, preferably performed by the patient alone. A safe, efficient, and user-friendly apparatus has been developed to permit Ultrashort Daily Auto Dialysis (UDAD). PMID- 2597519 TI - Effect of erythropoietin administration on blood and plasma viscosity in hemodialysis patients. AB - The effect of recombinant human erythropoietin (EPO) on whole blood and plasma viscosity was studied in six anemic hemodialysis (HD) patients, and five equally anemic placebo treated HD patients. Viscosity was determined pre- and postdialysis using cone-plate viscometry. Predialysis values for hematocrit and whole blood viscosity increased significantly over a 12 week period in the EPO but not the placebo treated group; plasma viscosity did not change in either group. Whole blood viscosity measured before and after a single HD session during week 12 revealed a significant rise. This change, expressed as a percent of the predialysis values, was similar in the two groups. Thus, the rise in whole blood viscosity seen in EPO treated patients is a result of the increase in erythrocyte concentration and not a result of an effect of EPO on plasma. In addition, EPO does not seem to alter the acute effect of HD on blood viscosity. PMID- 2597520 TI - Measurement of hemodialysis access recirculation: a two-needle method at the start of dialysis. AB - Conventional methods of measuring recirculation in hemodialysis access include a three site method performed during dialysis, and a two site technique conducted at the end of a hemodialysis treatment. This study describes a two site procedure performed at the beginning of a hemodialysis session. Blood samples are drawn from the arterial side of the hemodialysis access immediately prior to hemodialysis (AIPD), and from the same arterial line (A+5) and venous line (V+5) when maximal blood flows are reached 5 min after starting hemodialysis. Blood urea nitrogen (BUN) is measured in these samples, and the results entered into the formula AIPD - A+5/AIPD - V+5 X 100% to calculate the percent recirculation. Percent recirculation calculated by this method compared favorably with, and may hold several advantages over conventional techniques. PMID- 2597521 TI - Post to predialysis plasma urea nitrogen ratio, ultrafiltration and weight to estimate K.t/V. Use in auditing the amount of dialysis being administered. AB - The formula -In (R - 0.03 - UF/W), where R is the ratio of the postdialysis to predialysis plasma urea nitrogen level, UF the ultrafiltrate volume per session, and W the postdialysis weight, has been shown by us to estimate K.t/V accurately. We audited the amount of dialysis being administered in a moderate size outpatient unit in which urea kinetic modeling was not being done and in which 4 hr dialysis at a 250 or 300 ml/min blood flow rate was routinely prescribed. R was determined once per month on each of six successive months, and standard three point urea kinetic modeling was done on all patients once. R was quite reproducible in each patient, with a coefficient of variation of 6.6% +/- 3.2 standard deviation (SD). The R:UF:W-derived K.t/V averaged 0.91 +/- 0.19; the R:UF:W-derived K.t/V correlated with the modeled K.t/V (r = 0.98), with a mean percent error of only 0.12% +/- 3.6. A negative correlation (r = -0.56) was present between the R:UF:W-derived K.t/V and postdialysis weight; 9 of 40 patients had K.t/V values below 0.8 and 7 of these 9 weighed more than 85 kg. In 13 other patients, K.t/V was between 0.8 and 0.9. After inclusion of residual renal function (Kru) to calculate KT, KT was still below 0.9 in 19 patients. The main cause of underdialysis was inadequate prescription. The results suggest that monthly monitoring of R, with inclusion of UF and W to estimate K.t/V, is one useful quality assurance tool to assess the amount of dialysis being administered. PMID- 2597522 TI - Ultrafiltration of dialysis fluid for hemodialysis. AB - Since the quality of water in dialysis fluid varies considerably, and, in view of the fact that endotoxin or active derivatives can cause acute side effects in patients, the dialysis fluid must be sterile. The predialyzer fluid in 20 hemodialysis patients was investigated. Bacterial loading was between 5/ml and 5,000/ml, and the endotoxin concentration was high and extremely variable. After ultrafiltration of the dialysis fluid by a polyamide hollow fiber membrane, all samples were free of bacteria, and the concentration of endotoxin was lower than the detectable limit. With this procedure we can obtain sterile dialysis fluid, which is endotoxin free. PMID- 2597523 TI - Dialysate contamination and back filtration may limit the use of high-flux dialysis membranes. AB - Endotoxins, or fragments thereof, can reach the blood stream of dialysis patients, transported by diffusion and connection across the intact high-flux membrane. This transfer depends upon the phenomenon of back filtration. Back filtration generally occurs under conventional high-flux dialysis conditions with membranes having an ultrafiltration coefficient in blood (UF-C) above 20 ml/hr/m2/mmHg. The clinical consequences of back filtration vary from center to center depending primarily on the quality of dialysate. We therefore surveyed the bacterial and endotoxin levels of purified water and effluent dialysate in a cross section of dialysis centers in the central United States. Using a high recovery medium, we found that 53% of the centers had bacterial counts above the Association for the Advancement of Medical Instruments standard in water (20% cfu/ml) and 35% above the standard in dialysate (2,100 cfu/ml). Endotoxin concentrations higher than 5.0 EU/ml in both water and dialysate were found in 4% and 11.8% of the centers, respectively. Since high-flux membranes are believed to be of benefit for long-term dialysis patients, manufacturers will have to offer dialysate preparation systems with additional safety features. The proper membrane design will be a key to the success of such systems. PMID- 2597524 TI - Control of water flux in a bioartificial kidney. AB - UC-PK1 cells were grown to confluence on microporous microcellulose membranes in order to test the feasibility of using transmembrane pressure (TMP) for controlling connective water transport in a bioartificial kidney. TMP was applied on either the apical or basal aspect of the polarized cell layer, while the fluid compartments on both sides of the membrane were perfused with tissue culture medium in a miniature flow chamber. The cell monolayer did not allow filtration in the apical to basal direction when positive TMP up to 30 mmHg was applied on the apical side. Application of positive TMP on the basal side led to measurable ultrafiltration. The hydraulic permeability, L(p), of the cell-seeded membranes was found to be increasing with time, reaching a steady state value after 60 min. There was a strong positive correlation between L(p) and applied TMP. For a constant TMP, L(p) was found to be independent of the shear rate between 2.6 and 10.5 sec-1. When positive pressure was changed abruptly back from the basal to apical site, the ultrafiltration rate decreased to zero within seconds. Morphologic studies suggest that the tight junctions between cells were broken by TMP applied on the basolateral aspect of the cell monolayer. It is concluded that, basolateral TMP may be used to control water flux in a bioartificial kidney. PMID- 2597525 TI - Characteristic profiles of circulating blood volume during dialysis therapy. AB - From continuous measurements of the hemoglobin concentration in the arterial blood line during 50 hemodialysis sessions in 20 stable dialysis patients, the influence of the amount of ultrafiltered fluid, the ultrafiltration rate, and overhydration of the patient upon the circulating blood volume was derived. If ultrafiltration is stopped, blood volume increases until equilibrium is obtained. The amount of refilling is proportional to the ultrafiltration rate [2.5%/(L/hr)]. The decrease of blood volume after re-equilibration depends upon the ultrafiltered amount and the degree of overhydration. The mean decrease of blood volume per liter of ultrafiltrate was found to be 5.5% for an average overhydration of 3 L. PMID- 2597526 TI - Disappearance of oxidative damage to red blood cell membranes in uremic patients following renal transplant. AB - Hemodialysis patients display increased oxidative damage to red blood cell (RBC) membranes, characterized by elevated levels of malonyldialdehyde (MDA), a short chain aldehyde produced by the oxidation of the polyunsaturated fatty acids (PUFA) in the RBC membranes. This is the result of a metabolic blockage of the pentose-phosphate shunt in uremic patients, which causes reduced detoxification of highly oxidative free radicals. The oxidative damage induces increased RBC rigidity and decreased RBC deformability, therefore favoring hemolysis. The aim of this work was to determine if a functioning renal graft would restore normal erythrocyte metabolism, reducing the oxidative damage. To this end, we have determined RBC MDA concentrations in 20 hemodialysis (HD) patients (RBC MDA 18.22 +/- 4.36 micrograms/ml packed RBC), 20 renal transplant (T) patients with well functioning grafts (serum creatinine less than 2 mg%) (RBC MDA 1.2 +/- 0.4 micrograms/ml packed RBC) (T vs. HD P less than 0.005) and 20 healthy controls (HC) (RBC MDA 1.44 +/- 0.6 micrograms/ml packed RBC) (HC vs. HD P less than 0.005; HC vs. T NS). Our findings show that a well-functioning renal graft restores normal RBC metabolism and eliminates the oxidative damage induced by uremia. PMID- 2597527 TI - Mechanical circulatory support for perioperative donor heart failure. AB - Perioperative acute donor heart failure can be caused by various factors, such as recipient pulmonary hypertension, marginal donor heart function, or immunologic mismatch. Of 265 patients who underwent orthotopic transplantation, four received mechanical support for acute perioperative donor heart failure. In two patients with reactive pulmonary hypertension, right heart bypass (RHB) with a centrifugal pump was used for 53 and 36 hr, respectively. One patient who experienced biventricular donor heart failure was supported for three days with an intraarterial, transvalvular, axial-flow left ventricular assist device (LVAD). Circulation was supported effectively with the LVAD, despite an initial absence of right ventricular function. The fourth patient, who had signs of heart failure, received intraaortic balloon pump support for 24 hr after transplantation. All four patients were weaned from circulatory support, and heart function was restored in each; the mean left ventricular ejection fraction was 63% (range from 57 to 71%). One patient died of fungal infection 14 days after being weaned from pump support, another died of lymphoma two months after support was discontinued, and the remaining two patients are well 9 and 18 months after transplantation. In cases of acute donor heart dysfunction, temporary mechanical assistance is a reliable option for supporting the circulation during heart recovery. PMID- 2597528 TI - Multi-institutional studies of the National Cardiovascular Center Ventricular Assist System: use in 92 patients. AB - A ventricular assist system (VAS) developed at the National Cardiovascular Center (NCVC) and produced by Toyobo Company has been clinically evaluated at 32 institutes. The system consists of a pneumatic and diaphragm-type pump, and a control-drive unit with an automatic bypass flow (BF) control system. The VAS was used in 85 adults and 7 children with acute, severe heart failure. Forty-eight patients were weaned from VAS, and 21 were long-term survivors. Heparin was not used when BF was above 2.0 L/min in an adult sized pump, and 0.8 in a pediatric one. Thrombus formation was noticed in the groove around the valve in eight cases, and in the pump in eight. Pump-originated serious complications were not seen. Hematologic and biochemical findings revealed that the VAS did not directly affect the major organs. The control-drive unit, including the automatic BF control system, functioned accurately, with less manpower, securing reliable control over the circulation. Two major causes of death were irreversible heart failure, and multiple organ failure, which resulted from delayed application. In conclusion, the NCVC-type VAS has been found effective and reliable, less thrombogenic, and requiring less manpower for its clinical use. PMID- 2597530 TI - Evaluation of right ventricular function during clinical left ventricular assistance. AB - Hemodynamic and mechanical parameters of right ventricular (RV) performance were measured in eight patients undergoing left ventricular (LV) assistance as a bridge to cardiac transplantation. All patients, even those with impaired RV performance, survived support and transplantation. The reduction of LV afterload produced by the left ventricular assist system (LVAS) results in RV afterload reduction, which permits even the marginal RV to function adequately during LVAS support. PMID- 2597529 TI - Left ventricular function in patients with centrifugal left ventricular assist device. AB - We used blood pool radionuclide angiography to study the left ventricular (LV) ejection fraction (EF) in 17 patients with a centrifugal assist device (AD) placed because of severe postoperative LV dysfunction. During maximal LVAD flow, the 12 patients who could be weaned had a higher LV-EF than the 5 who could not be weaned (18 +/- 12% vs. 9 +/- 2%, p = 0.04). Sequential studies during variable AD flows in 12 patients revealed an increase in LV-EF from 15 +/- 7% at maximal flows to 33 +/- 8% during minimal flows (p less than 0.005) in the 10 patients who could be weaned and no change in LV-EF in 2 patients who could not be weaned. The LV-EF during maximal LVAD flow rates was similar in the 10 patients with long term survival (192 +/- 129 days) and in the 7 patients with only short-term (9 +/ 6 days) survival (LV-EF 17 +/- 12% vs. 12 +/- 6%, p = ns). The long-term survivors, however, had a substantial increase in LV-EF from 20 +/- 13% to 34 +/- 9% (p less than 0.01), as the LVAD flow was decreased from maximal to minimal, whereas the short-term survivors had an insignificant increase in LV-EF from 12 +/- 7% to 21 +/- 12% (p = ns). The long-term survivors increased the LV-EF from maximal to minimal LVAD flows by 182%, in contrast with the short-term survivors, who increased the LV-EF by only 44%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2597532 TI - Development of hybrid compliant graft: rapid preparative method for reconstruction of a vascular wall. AB - This paper presents a rapid preparative method of vascular wall reconstruction using a compliant artificial graft. The architecture of a hierarchically structured vessel wall composed of a "biomimic" intima, a basement membrane, and media was produced using step-by-step reconstruction. Electron microscopic observation of transverse sections of the reconstructed vessel wall showed a four layered structure: monolayered endothelial cells as an intima; an artificial basement membrane composed of a collagen fiber matrix complexed with dermatan sulfate; a medial composed of smooth muscle cells embedded in collagen fiber nets; and an open-cell structured microporous compliant artificial graft as a structural matrix. The tissue-engineered structure, with a complete and morphologically intact lumen covered with endothelial cells, imparts biologic function. Thus, the tissue engineering approach promises to provide rapid construction of a viable bioartificial vessel. PMID- 2597531 TI - Right ventricular failure during clinical use of a left ventricular assist device. AB - The purpose of this study is to describe the authors' clinical experience of RVF during LVAD pumping and to delineate the effect of LVADs on RV function, with special reference to the level of myocardial recovery. Pneumatically driven LVADs were used on a total of 13 postoperative cases for 18 hours to 70 days (mean, 9.9 days). The RVF, which was defined as increased right atrial pressure (RAP greater than or equal to 20 mmHg) during LVAD pumping, were experienced in four cases (two ischemic, two valvular). Duration of the RVF ranged from 3 hours to 8 days (mean, 3.0 days) and the maximum RAP ranged 22-30 mmHg (mean, 27 mmHg). The effects of LVAD pumping on the RV function were delineated during serial pump on pump off studies in two cases with RVF and three cases without RVF, in relation to off/on ratio of the systolic aortic pressure (AOP off/on), which worked as an indicative parameter of myocardial recovery. Each pair of on/off data were assigned to four groups according to AOP off/on and complication with RVF, and mean percentage changes of mRAP and PAP were compared. The RAP of RVF cases were significantly increased by 16% with the LVAD pumping when the AOP off/on was below 0.7, whereas PAP invariably decreased in most cases. The results indicated that the LVAD suppressed the RV function before the myocardial recovery and when the heart was complicated with RVF. PMID- 2597533 TI - Compliance effect on patency of small diameter vascular grafts. AB - The compliance mismatch hypothesis as a cause of failure of small diameter grafts was investigated using 4 mm internal diameter, 5 cm long Biolized polyurethane grafts. The luminal surface of 0.5 mm thick Biomer sponge grafts was covered with 100 microns of crosslinked gelatin. Compliance matched, and noncompliant grafts had in vivo compliance values of 13.5 +/- 2.89 and 1.0 +/- 0.7 X 10(-2%) per mmHg, respectively. In vivo compliance defined as 2 X dD/dP X 1/Do was measured in situ using the ultrasonic Hokanson probe. Compliance values of compliant grafts equaled that of the canine carotid artery at 100 mmHg mean arterial pressure. Grafts were implanted using an end-to-end anastomosis in 14 dogs for 6 wk. Patency rates for compliant vs. noncompliant grafts were 64% (9/14) and 50% (7/14). Compliance values for compliant grafts decreased to a mean of 7.14 X 10( 2%) per mmHg. Anastomotic intimal hyperplasia at the proximal and distal ends of compliant and noncompliant grafts measured 239.9 +/- 128, 197 +/- 129 microns, 338.9 +/- 273.6, and 304.3 +/- 179.3 microns, respectively. There were no significant differences in localized anastomotic intimal hyperplasia at either graft end for either graft type. This study did not show any positive effects of graft compliance. PMID- 2597534 TI - Platelet interactions with heparin binding growth factor and fibronectin. AB - A fibronectin (Fn)/heparin/heparin binding growth factor (HBGF)/heparin (FHHH) complex can be affixed to vascular grafts. This study examines the effect of HBGF, Fn, and FHHH on platelet adhesion and aggregation. Expanded polytetrafluoroethylene (PTFE) grafts (5 cm X 4 mm) were treated with Fn (n = 9), FHHH (n = 9), or neither (n = 10) and interposed into canine aortoiliac systems, using each dog as its own control. Autogenous radiolabeled (111In oxine-650 muCi) platelets were injected IV prior to re-establishment of circulation. Blood flow was determined by electromagnetic flowmetry and perfusion maintained for 30 min. Grafts were removed with native aorta and ipsilateral iliac arteries (IIA). Specimens, excluding anastomoses, were sectioned for gamma counting and computerized planimetry. Results showed that FHHH and Fn treated grafts contained significantly more radioactivity than control segments, when normalized to their IIA. FHHH treated grafts contained 27 +/- 16 times more radioactivity per mm2 than IIA, Fn treated prostheses 12 +/- 8 times more, and untreated PTFE 4 +/- 3 times more. FHHH was significantly more radioactive than Fn alone (p less than or equal to 0.03). Platelet aggregation in response to either Fn or HBGF was studied in vitro. Aggregation was not activated by either Fn (1-100 micrograms/100 microliters) or HBGF (25-2,500 ng/100 microliters). These data suggest that Fn and HBGF promote platelet adhesion but not aggregation. PMID- 2597535 TI - Therapeutic plasmapheresis for liver failure after hepatectomy. AB - Therapeutic plasmapheresis (PP) for liver failure following the resection of primary liver cancer was evaluated retrospectively. PP was repeated two to three times per week using plasma exchange (PE) with fresh frozen plasma as a substitution fluid in all eight cases and direct hemoperfusion (DHP) in two cases. PE effectively decreased serum bilirubin and/or improved hepatic encephalopathy in six of eight patients and prolonged survival time (p less than 0.05, chi-square test). DHP was not effective. Liver failure following the resection of damaged liver differs from acute liver failure in both the condition itself and the reaction to PP. Fractionation of serum bilirubin using high performance liquid chromatography showed differences in the ratio of delta bilirubin in one survivor versus two who died and was effective in selecting a patient who would respond to PE. In conclusion, PE is effective in prolonging survival time after liver failure in hepatectomized patients compared to conventional therapy. PMID- 2597537 TI - Temperature dependent protein removal by large pore membrane filtration. AB - The high cost and clinically associated side-effects of plasma exchange treatment warrant development of on-line plasma fractionation techniques. Cryoglobulin removal from cryoglobulinemic plasma is particularly amenable to membrane filtration in the cold (cryofiltration). Temperature effects on filtration were studied in vitro using a large pore (nominal average size, 3 microns), low surface area (0.14 m2) filter. Plasmas with high concentrations of cryoprecipitable proteins (CPP; greater than 1.1 micrograms/ml) and immune complexes (IC; greater than 400 U/ml) were obtained from consenting cryoglobulinemic patients by plasma exchange. Removals of IC and CPP were highly temperature dependent, and high ratios of IC, CPP, and albumin removal were achieved (e.g., sieving coefficient [SC] = 0.05 and 0.91 for CPP, and SC = 0.94 and 0.95 for albumin at 4 degrees C and 23 degrees C, respectively). Clinically required volumes of plasma (greater than 2L) were processable. Cryofiltration with this new, high performance cryoglobulin filter is selective and may substantially reduce the clinical need for plasma replacement products. PMID- 2597536 TI - Performance of a new hybrid artificial liver support system using hepatocytes entrapped within a hydrogel. AB - To develop a hybrid artificial liver support system (ALSS), the authors constructed a rotating-disk type ALSS using hepatocytes entrapped within a calcium alginate hydrogel. This module was designed in imitation of the gas liquid contactor that uses the same principle. Forty disks with film-shaped hydrogel were mounted to a horizontal rotating axis and were kept in contact with blood. The concentration of hepatocytes in the gel varied from 1.9 X 10(9) to 1.7 X 10(10) cells/L gel. Entrapping hepatocytes within hydrogel kept the hepatocytes viable, and results of in vitro experiments showed ammonium metabolism and urea synthesis. The results of ex vivo perfusion experiments using cats with acute hepatic insufficiency indicated that this module had the ability to replace liver function in vivo. PMID- 2597538 TI - Hemofiltration and plasmapheresis in newborns using a small blood pump system. AB - Extracorporeal detoxification methods in newborns and premature infants are unavailable and contraindicated because of technical problems. The authors' experiences with a blood pump unit that was miniaturized for hemodialysis, hemofiltration, and plasmapheresis in newborns are reported. In 28 newborns and premature infants, 32 hemofiltrations, 3 hemodialyses, and 57 plasmaphereses were carried out for different diseases. Thirteen of 28 patients died despite hemofiltration and/or plasmapheresis as a result of their primary disease and/or immaturity, and 15 patients improved. PMID- 2597539 TI - Long-term clinical experience with HELP-LDL-apheresis in combination with HMG-CoA reductase inhibitors for maximum treatment of coronary heart disease associated with severe hypercholesterolemia. AB - Extracorporeal low density lipoprotein (LDL)-apheresis offers an adjunctive therapy to diet and drug treatment for reducing LDL concentrations in patients with excessively high cholesterol levels and those at high coronary risk. After nearly 4 years experience with the heparin-induced extracorporeal LDL/fibrinogen precipitation (HELP) system, based on heparin induced LDL precipitation at acidic pH, over 7,000 single aphereses have been performed on more than 100 patients in several clinics. Due to the simultaneous removal of LDL and fibrinogen, regular HELP-LDL-apheresis can normalize hemorrheologic parameters, thus explaining the observation of a rapid and lasting clinical improvement in signs and symptoms of coronary heart disease (CHD). The use of Simvastatin in combination with HELP significantly augments the reduction in LDL cholesterol to a level where regression of atherosclerotic lesions might be expected. PMID- 2597540 TI - Splanchnic volume, not flow rate, determines peritoneal permeability. AB - To distinguish the effects of splanchnic blood flow rate from those of splanchnic volume on peritoneal transfer rates, measurements were made in rabbits before and after intraperitoneal exposure to sodium chromate. The sodium chromate induced reversible hepatic sinusoidal block with consequent portal venous congestion and stasis, which was demonstrable on histologic sections. Concurrently the ultrafiltration rate, and ultrafiltration coefficient each doubled after chromium even though the dialysate reabsorptive rate increased and the absorptive diffusion of glucose was at least as high as in control dialyses. Chromium induced significant increases in mass transfer coefficients of urea, potassium and phosphate and in protein clearance. These data suggest that splanchnic volume is an important determinant of peritoneal transfer functions and that the hepatic capillaries may contribute appreciably to transfer ordinarily ascribed to peritoneal capillaries alone. PMID- 2597542 TI - Development and clinical application of a new CAPD connection system--Safedap. AB - To perform continuous ambulatory peritoneal dialysis (CAPD), a safe and easy bag exchange system must be established. The authors developed a new system called "Safedap" and applied it to clinical cases. Safedap consists of a bottom, a sleeve, a shell, and a lock-type connector. The bottom and sleeve are made into one unit with a preembedded sponge saturated with 10% povidone-iodine for disinfection and protection. Safedap was introduced to 23 patients who were observed for a period of 293 patient months. Sixteen patients used a standard spike and functioned as controls. Peritonitis rates were 1/73.3 patient months in Safedap (4 episodes in 3 patients) and 1/30.1 patient months in controls (10 episodes in 7 patients; p less than 0.05). Using life table analysis, the probability of a control being peritonitis free at 12 months was 0.63 versus 0.95 in those using Safedap (p less than 0.05). By allowing completion of bag exchanges safely and rapidly, Safedap is effective in reducing the occurrence rate of peritonitis. PMID- 2597541 TI - Periodic elevation of complement activation products in peritoneal dialysis effluent. AB - Peripheral white blood cells (WBCs) of chronic ambulatory peritoneal dialysis (CAPD) patients show a reduced expression of chemotactic receptors and a desensitization to chemotactic factor induced events. Chronic complement activation has been suggested as a cause of such phenomena, resulting from either uremia, the indwelling peritoneal catheter, and/or dialysis fluid stimulation. The presence of complement activation products in peritoneal dialysis effluent was assessed by longitudinal measurement of C3bi in eight patients over a 6 to 8 month period, while peritoneal polymorphonuclear leukocyte (PMN) and monocyte CR3 and C5a receptor expression was quantitated by flow cytometry. In six of eight patients, C3bi levels were stable over time and usually measured less than 5 micrograms/ml. Two other patients showed periodic elevation of C3bi, which was not associated temporally with peritonitis. Further study is required to identify the origin of such activated complement components within the peritoneal cavity. However, no correlation was found between dialysate C3bi levels and peritoneal PMN or monocyte expression of CR3 or C5a receptors. Furthermore, the incidence of peritonitis for the two individuals with elevated C3bi was discordant (1 episode/8 patient months vs. 0 episodes/32 patient months), suggesting little or no relationship between these parameters. PMID- 2597543 TI - Factors contributing to oxalate deposits in the myocardia of hemodialysis patients. AB - Although the deposition of calcium oxalate crystals in the myocardium can be associated with significant morbidity and mortality in hemodialysis patients, the pathogenesis of this deposition is not known. The present study was undertaken in order to clarify the contributing factors in an experimental setting. A simple increase in plasma oxalate levels did not cause deposits in the heart, nor did elevated values of plasma ionized calcium appear to be important in chronic renal failure. Following heterotopic cardiac transplantation, a much larger deposition of crystals was identified in the heart allograft that was histologically damaged by rejection. These findings suggest that the state of the local tissue is a very important factor in the deposition of oxalate crystals. PMID- 2597544 TI - Heparin-free hemodialysis with a polyacrylonitrile membrane. AB - The low in vitro thrombogenicity of polyacrylonitrile (AN-69) membrane may offer the possibility of performing hemodialysis (HD) with little or no heparin. The authors sought to reduce heparin dosage using AN-69 dialyzers at blood flows of 400 to 600 ml/min. Over a 90 day period, 2228 HDs were performed: 1531 (69%) with AN-69, 528 (24%) with regenerated cellulose (RC), and 169 (8%) with cellulose acetate (CA) dialyzers. Two hundred and eighty-three HDs were performed without systemic heparin; blood compartments were prerinsed with 2,000 U heparin in 1,000 ml of 0.9% saline. Saline flushes were used in cases of rising venous drip chamber pressures or visible clotting. Incidence of clotting overall in AN-69 HDs was 0.52% (8/1531), 2.8% (15/528) with RC, and 11.2% (19/169) with CA. In heparin free HDs, incidence with AN-69 was 1.3% (3/230), 28.6% with RC (4/14), and 25.6% with CA (10/39). AN-69 remained less thrombogenic when HDs were stratified by blood flow rate and vascular access was used. Urea clearance was no different in conventional and heparin-free treatments. Blood flow rates of 400 ml/min or higher had an independent antithrombogenic effect. It was concluded that the combination of high blood flow with AN-69 membrane allows marked reduction of HD heparin dose and safe routine use of heparin-free HD. PMID- 2597545 TI - Clinical experience with the Hemopump. AB - Complications associated with surgical procedures generally required for implantation of left ventricular assist devices (LVADs) may limit them from providing adequate circulatory support for patients suffering from profound left ventricular failure (LVF). Such problems are minimized with the use of the Hemopump, a recently developed intraarterial LVAD. This 7 mm transvalvular axial flow blood pump is percutaneously powered by an external console with a flexible drive cable. Since April 1988, we have used the device effectively in 12 patients. Indications for device application included postcardiotomy shock in eight patients, acute allograft rejection in two, severe allograft failure in one, and acute myocardial infarction in one. The Hemopump was inserted from the femoral approach in eight patients, the ascending aorta in three, and the abdominal aorta in one. During the first 12 hr of support, cardiac index (CI) ranged from 1.14-2.98 L/min/m2, and pump flow was 3.0 to 3.6 L/min. As the patients' hearts recovered, the pump speed was gradually reduced. Circulatory support ranged from 26 to 139 hr; 10 of 12 patients were successfully weaned. The mean CI before device removal was 2.74 +/- 0.4 L/min/m2, and the pump flow was 2.14 +/- 0.69 L/min. No device-related infections or thromboembolic episodes occurred. Plasma-free hemoglobin remained within acceptable levels during pumping. Six patients survived more than 30 days after pump removal. Thus, the Hemopump can provide safe, stable, temporary circulatory support and can be expeditiously applied with minimal complications. PMID- 2597546 TI - Experimental evaluation and clinical application of a pediatric ventricular assist device. AB - A pneumatic pediatric ventricular assist device (VAD) with a stroke volume of 20 ml has been developed to treat post-operative heart failure (HF), and maintain transplant candidates. The polyurethane VAD has two #21 Bjork-Shiley valves and the internal diameter of the cannula is either 6 or 8 mm. Hemodynamic effects of a left ventricular assist device (LVAD) on a HF after Fontan's procedure model, and those of a right ventricular assist device (RVAD) on right HF with pulmonary hypertension model, were investigated in acute experiments with four and five dogs, respectively. In the former, the pressure gradient across the lung and cardiac output (CO) increased with an LVAD; right atrial pressure decreased and CO increased with an RVAD in the latter. The pump was implanted as an LVAD in 8 young goats, 9-22 kg in weight, for 4-10 weeks and favorable in vivo performance was demonstrated. The VAD system was applied as an LVAD to two postcardiotomy patients, a 12 kg boy with a ventricular septal defect, and a 13 kg boy with an endocardial cushion defect. In these cases, CO was well maintained at the level of 2.5-4.1 L/min/m2 for three and seven days, respectively, and the pump was removed. In conclusion, this VAD will become a promising circulatory support system for pediatric uses. PMID- 2597547 TI - Left ventricular assist system with a simplified cannulation technique. AB - A simplified cannulation system was developed without thoracotomy for a ventricular assist system (VAS) that will be applicable even in an emergency. This system consists of an air driven and diaphragm type pump, cannulae, and devices for insertion. The inlet cannula was inserted into the left atrium through the femoral vein using a modified brockenbrough transseptal method. This system was installed without thoracotomy in a chronic experiment in two goats and was removed without any trouble after 14 days of pumping. In a 40 day experiment with this system implanted between the left atrium and the aorta, bypass flow was maintained at 2.7 to 3.3 L/min, and plasma free hemoglobin levels were below 7 mg/dl. When this system was implanted between the left atrium and the aorta, and activated in an induced heart failure goat, output through the pump was 3.0 +/- 0.4 L/min, and mean aortic pressure was increased to 91.7 +/- 15.9 mmHg from 55.8 +/- 15.4 mmHg. This system takes a middle position between an IABP and VAS with thoracotomy in capability of circulatory support and convenience. PMID- 2597548 TI - Characteristics of blood rheology in patients during Novacor left ventricular assist system support. AB - Blood rheologic properties were studied in 11 patients on Novacor LVAS support (1 126 days) as a bridge to transplantation. Overall, these patients showed slight increases in mean blood viscosity and red cell rigidity. Their mean plasma fibrinogen was in the upper normal range. However, the degree of rheologic change observed, and the individual factors affected most, were unique to each patient and hemorheologic results correlated well with the patient's clinical status. PMID- 2597549 TI - Extended clinical support with an implantable left ventricular assist device. AB - Clinical evaluations are under way of an intracorporeal (abdominally positioned) pulsatile left ventricular assist device (LVAD) that is capable of providing support for extended periods (greater than 30 days) in patients awaiting heart transplantation. The LVAD, developed by Thermo Cardiosystems Inc. (Woburn, MA), has uniquely textured blood contacting surfaces and requires only minimal antithrombotic therapy. It has been used at the Texas Heart Institute as a bridge to transplantation in 11 patients, including 2 who are currently receiving support. Four patients required extended LVAD support (35-132 days); of those, three are doing well at 1.5, 8.5, and 13 months, respectively, after transplantation, and one died of liver failure 49 days after transplantation. The LVAD was operated in a fixed-rate mode to maintain pump flows at 4-8 L/min, resulting in stabilization of hemodynamic and secondary organ function in all patients. Blood chemistry and hematologic values returned to normal during LVAD support in three of four patients. Postoperative anticoagulation was gradually reduced over the course of the trials. The two most recent patients (35 and 132 days) received only oral dipyridamole (75 mg X 3/day) and aspirin (80 mg/day) after the early recovery period (four-six days), resulting in normal prothrombin and partial thromboplastin times. Plasma hemoglobin levels remained within acceptable limits, and there was no evidence of thromboembolism. Blood contacting surfaces were coated with a thin, adherent, biologically derived lining. The initial results indicate that the intracorporeal LVAD, with textured blood contacting surfaces, can effectively support the failing heart for extended periods (greater than 30 days) with minimal antithrombotic therapy. PMID- 2597550 TI - Thromboembolic complications with the Pierce-Donachy ventricular assist device. AB - Pierce-Donachy ventricular assist devices (VADs) were used to support 54 patients. None of the 27 patients supported less than 4 days had any visible thrombi in the VAD at explant. Of the 27 patients supported longer than 4 days, nine patients had visible thrombi. In this group of 27 patients, 19 received VAD support pending myocardial recovery, and anticoagulation consisted of dextran (4 15 days) and heparin during the weaning phase (1-2 days). The other eight patients had VADs implanted as bridges to cardiac transplantation. These patients also received dextran postoperatively (1-5 days), but were switched to a regimen of oral warfarin and dipyridamole. Duration of support for the nine patients in whom thrombi were found ranged from 4-27 days (mean, 12 days). The etiology of thrombus was probably related to mechanical problems in four patients, inadequate anticoagulation in two patients, sepsis in two patients, and unknown causes in one patient. Four of these patients suffered cerebral or peripheral injuries, which were probably embolic in two, and possibly embolic in two. One of these four patients survived, and two patients with thrombi but no emboli survived. One patient suffered a stroke, but no evidence of thrombi was found. Our incidence of thrombus with this VAD was 17%. Thrombi were related to inadequate anticoagulation, interrupted flow, or sepsis, but not to duration of support. PMID- 2597552 TI - An analysis of thermal regulation in hemodialysis with one and three compartment models. AB - A one compartment model of heat kinetics in hemodialysis (HD) was formulated, solved for the body surface heat transfer coefficient, and used to analyze reported clinical data. The analysis showed a linear relationship between percent change in body surface (y) and fractional dialyzer (x) heat loss, such that y = 25 - 44X, p less than 0.001. Thus, when X = 0, surface heat loss decreases 25% and core temperature (T) rises, and X must equal 45% of heat production to stabilize core T during HD. A three compartment model predicts that skin clothing insulation will have to increase 2.5 times to avoid thermal discomfort when X = 45% of heat production. A theoretic mechanism for decreased symptomatic hypotension resulting from stabilization of core T is proposed. PMID- 2597551 TI - The wish for renal transplantation. AB - The authors studied the wish for renal transplantation in 268 patients on chronic dialysis. One hundred forty (66%) of 268 patients wished for a transplant, while 71 (34%) did not wish to have one; the wish was not known in 57 (22%) of the patients. Sixty-five percent of the women and 67% of the men wanted to be transplanted. The wish for transplantation was negatively correlated with age. Thus, 78% of the patients below 50 years of age wished for a transplant, versus only 37% of those more than 70. Center patients wished more often for a transplant than patients on self dialysis (68% vs. 59%), but the difference was not significantly different except in patients over the age of 50. The chance of fulfillment (the % transplanted over the % of those who wished to have a transplant) declined with age. While 90% of the patients below age 50 who wished for a transplant could expect to receive one, only 41% of the patients over age 70 who wished for one could expect to receive one. Older patients were also less often asked about their wish. While the wish for a transplant was known in more than 90% of the patients under 50 years of age, it was known in less than one half of those over 70. This investigation shows that the wish for renal transplantation is related to age and mode of dialysis, but not sex. Old patients are often not asked about their preference for mode of treatment. PMID- 2597553 TI - Oxalate crystal deposits in renal tubules and cystic changes in 5/6 nephrectomized and normal rats. AB - Although the mechanism responsible for the genesis of acquired renal cysts in hemodialysis patients has not been clearly defined, the authors suggested that obstruction of the nephron by deposition of oxalate crystals may be an important factor. The present study was undertaken to examine this possibility in an experimental setting. Ten 5/6 nephrectomized rats were given daily subcutaneous injections of 5 mg sodium oxalate and allowed free access to saccharin sweetened water containing 2 mg/ml sodium oxalate. Six other 5/6 nephrectomized rats were controls. In addition, eight healthy rats received 10 mg sodium oxalate for 30 days. The earlier appearance and severe degree of tubular dilatation in oxalate treated 5/6 nephrectomized compared with untreated 5/6 nephrectomized rats and the presence of renal tubular dilatation with oxalate deposits in normal rats treated with oxalate sodium are likely to be due to tubular obstruction or stenosis caused by oxalate deposition. In conclusion, oxalate deposits in the renal tubules seem to be an important factor in the formation of acquired renal cysts in chronic renal failure. PMID- 2597554 TI - Atherosclerosis in uremic mice. AB - To study the possibility that susceptibility to the development of atherosclerosis during chronic renal failure is genetically determined, aortic lesion formation and changes in serum lipid levels in mice of 2 different inbred strains, C57BL/6J and A/J, were examined. Chronic uremia was induced by electrocoagulation of the right renal cortex and left nephrectomy. The mice were then fed either normal rodent chow or a saturated fat and cholesterol-enriched diet for 6 weeks. None of the A/J mice developed atherosclerosis, whereas the aortas of chow-fed uremic C57BL/6J mice were found to contain a number of fatty lesions, the severity of which was increased by a high fat diet. Uremia had different effects on serum cholesterol, triglycerides, and lipoproteins in the two strains. The results suggest that the resistance of A/J mice to uremia induced atherosclerosis may be attributed to their ability to maintain high serum HDL-cholesterol levels and/or low serum triglyceride levels. The results further indicate that the development of atherosclerotic lesions in uremic mice is both genetically determined and affected by diet. PMID- 2597555 TI - A novel approach to anticoagulation control. AB - Heparin used in extracorporeal therapy often leads to bleeding complications. Protamine used for heparin reversal can cause adverse hemodynamic responses. To control both types of complications, a cellulosic hollow-fiber filter device containing immobilized protamine (defined as a protamine filter) was developed. In vivo experiments with dogs showed that the filter not only removed more than 80% of the anticoagulant activity of heparin, but also caused no clinically significant hemodynamic response. In addition, the protamine filter also significantly attenuated both the thrombocytopenic and granulocytopenic responses associated with the use of protamine. Moreover, the use of immobilized protamine considerably reduced activation of the blood complement system by free protamine. PMID- 2597556 TI - Laboratory evaluation of a double lumen catheter for venovenous neonatal ECMO. AB - The authors designed and tested a 14F outside diameter thin-walled double lumen catheter (DLC) for neonatal venovenous (VV) extracorporeal membrane oxygenation (ECMO). In vitro tests with water and dye solution showed capacity of the drainage lumen was 1,096 ml/min at 100 cm siphon, and pressure drop across the perfusion lumen was 300 mmHg at 500 ml/min flow. Recirculation at 500 ml/min flow ranged from 5 to 29%, depending upon simulated cardiac output. The highest serum hemoglobin during 12 hour 400 ml/min flow VV bypass in five dogs was 49 mg/dl. Typical oxygen transport in four dogs was 25 cc/min at 400 ml/min flow. This catheter is well suited for clinical VV ECMO in neonates. PMID- 2597557 TI - Regional blood flow during extracorporeal membrane oxygenation in lambs. AB - To determine changes in blood flow to different organs during extracorporeal membrane oxygenation (ECMO), the authors performed venoarterial ECMO in four young lambs for 71-96 hr (Group 1). Macroaggregated albumin microspheres labeled with technetium 99m were injected through the perfusion cannula before termination of ECMO to determine percent of blood flow by measuring radioactivity from the microspheres lodged in specific organs. The control group (Group 2) consisted of three animals not on bypass; injections were made through a catheter placed in the left ventricle. Relative coronary blood flow from the perfusion cannula was significantly less than relative coronary blood flow in the control group, possibly because of cannula location. Renal flow from the perfusion cannula also was decreased. Contrary to observations in rabbits, cerebral perfusion did not decrease in the bypass group despite ligation of the carotid artery and the external jugular vein. There were no statistically significant differences between the two groups in the relative blood flow to other organs. The authors conclude that ECMO may significantly alter myocardial and renal perfusion, with minimal effects to other organs. PMID- 2597558 TI - Development of an intravascular lung assist device. AB - Intravascular lung assist devices (ILADs) must provide sufficient gas transport without excessive pressure drop. In vitro studies of fiber-bundle devices determined the effect of geometric configuration on gas transfer efficiency, the amount of surface area needed to achieve sufficient gas transport, and the relationship between gas transport and blood-side pressure drop. ILADs with cross flow fibers transfer at least 10 times more O2 than parallel flow ILADs of the same surface area, and six to eight times more CO2. Some tested devices with 0.4 0.6 m2 of surface area can transfer 100 ml/min of both O2 and CO2. Configurations with high gas transport, however, often require moderate pressure drops. PMID- 2597559 TI - Extracorporeal membrane oxygenation for percutaneous coronary angioplasty in high risk patients. AB - Improvements in percutaneous coronary angioplasty (PTCA) have broadened the scope of this therapy to higher risk patients. The authors used an extracorporeal membrane oxygenator (ECMO) system during seven PTCA procedures to provide rapid, safe, cardiopulmonary support for high-risk patients. Six patients underwent femoral cutdown and placement of arteriovenous cannulae before PTCA; one patient was cannulated percutaneously. In two patients, no ECMO support was used, whereas two of the remaining five patients were maintained on low flow (1.5 L/min) during the procedure and three patients were maintained with higher flows (average 3.0 L/min). All patients were removed from cardiopulmonary support with satisfactory hemodynamics and maintained on i.v. heparin for 12-48 hours. In six patients groin hematomas developed, in four deep venous thrombosis developed, and in one patient arterial occlusion after percutaneous cannulation developed. One patient died of retroperitoneal hemorrhage unrelated to the ECMO cannulation site. Six patients survived. This system can be rapidly deployed while providing satisfactory cardiopulmonary support. PMID- 2597560 TI - Quantitation of platelet loss with indium-111 labeled platelets in a hollow-fiber membrane oxygenator and arterial filter during extracorporeal circulation in a pig model. AB - Platelet consumption in a hollow-fiber membrane oxygenator (HFMO) and arterial filter (AF) during cardiopulmonary bypass (CPB) was quantified in five pigs using Indium-111 labeled autologous platelets. Platelet labeling was performed 20-24 hours before CPB. After general endotracheal anesthesia, the pigs were systemically heparinized and were placed on CPB via a median sternotomy. After 3 hours of CPB, radioactivity was quantified with a gamma camera and an ionization chamber. The percent of injected dose (mean +/- SD) was 0.79 +/- 0.45 in the HFMO, 2.52 +/- 0.93 in AF, 4.3 +/- 1.2 in blood loss during CPB. Platelet consumption in HFMO during CPB was lower than in bubble oxygenators (19%) or silicone membrane oxygenators (12%) as observed in previous studies. PMID- 2597561 TI - Aluminum toxicity and albumin. AB - During a study of priming solutions for extracorporeal membrane oxygenation (ECMO) in the intensive care nursery, it was discovered that those solutions using certain brands of 25% albumin contained aluminum levels within the toxic range. When the brand was changed to a brand known to have a lower aluminum (Al) content, a marked drop in priming solution Al levels was measured. The heat exchanger was examined as a possible source of soluble Al. No evidence of elevated Al levels was found in fluids perfusing this heat exchanger when compared with a stainless steel heat exchanger. The Al content of various blood products was evaluated along with various brands of 5% albumin and 25% albumin. PMID- 2597562 TI - Development of a novel artificial matrix with cell adhesion peptides for cell culture and artificial and hybrid organs. AB - The authors present a novel artificial matrix with high cell adhesion and growth rate that was produced by chemical fixation of an RGD-containing peptide (Arg-Gly Asp) on a polyvinyl alcohol (PVA) surface. The logical sequence behind the molecular design of an artificial matrix that mimics natural adhesive proteins, such as fibronectin, is based on the fact that an RGD tripeptidyl amino sequence is the minimal common adhesion site of adhesive proteins. Activation of surface hydroxyl groups by carbonyl diimidazole successfully incorporated GRGDSP (Gly-Arg Gly-Asp-Ser-Pro) onto PVA films. The resultant film surface was found to be bioactive, molecularly recognizing the adhesive receptor of bovine endothelial cells. Thus, the artificial matrix mimics active adhesion sites and serves as a novel artificial matrix that may be useful for cell culture, tissue-compatible implants, and hybrid artificial organs. PMID- 2597563 TI - An in vitro test model to study the performance and thrombogenicity of cardiovascular devices. AB - During the development of cardiovascular devices, it is necessary to evaluate their performance in vitro under experimental conditions that closely resemble their use in vivo. Therefore, an in vitro test model was developed to evaluate the performance of cardiovascular devices with blood. The in vitro test model consists of a pneumatically driven 50 cc polyurethane ventricle with either mechanical or experimental polyurethane tricuspid semilunar valves, connected to a horseshoe-shaped blood reservoir. A sampling port permits frequent removal of blood for hematologic evaluation. All the couplings are of the quick connect type to facilitate assembly and exchange of parts. The total volume of blood in the test model is approximately 1.4 L, and experiments are conducted in the absence of an air-blood interface. Except for mechanical valves and the chosen test interface, the entire blood contacting surface consists of polyurethane. Fresh bovine heparinized blood is used for the experiments. After filling the reservoir and the ventricle with blood, the concentration of heparin is adjusted with protamine to an APTT level of three times normal (80-100 sec). Once this level of anticoagulation is achieved, the blood is circulated for the next 2-3 hr at the desired test parameters (beats/min, cardiac output, etc.). A number of hematologic parameters are monitored during the test, including APTT, PT, plasma free hemoglobin and ADP-induced platelet aggregation. With the help of this model a number of devices, including experimental polyurethane tricuspid semilunar valves, Silastic tube valves, valves with heparin coated leaflets, and small (50 cc) experimental ventricles have been studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2597565 TI - Effect of membrane characteristics on the performance of Couette rotating plasma separation devices. AB - The concept of a cylindrical membrane rotating at high speed inside a concentric cylinder (Couette flow device) has proved to be very efficient for plasma separation from whole blood. The authors show that its high filtration velocity (about 0.5-0.6 cm/min) is due to the presence of Taylor vortices in the blood filled annular gap, which greatly increase the shear rates, but not radial migration of formed elements under centrifugal forces. The variation of filtrate velocity with transmembrane pressure (ptm) markedly depends upon the type of membrane. With a 0.8 micron polycarbonate membrane and bovine blood at 40% hematocrit, the filtration velocity reaches a peak equal to 0.6 cm/min at 3,000 rpm, then decreases to 80 mmHg, reaching a plateau of 0.35 cm/min independent of ptm. With a nylon membrane of 0.5 micron pores under the same conditions, the filtration velocity does not present a peak, but rises continuously to reach a 90 mmHg plateau equal to 0.5 cm/min. Similar behavior, but with lower plateaus, is also obtained with polycarbonate membranes at pore sizes below 0.4 microns. At 3,000 rpm, hemolysis occurs if ptm exceeds 750 mmHg, far above the operating range. PMID- 2597564 TI - Effects of surface integrity on the fatigue life of thin flexing membranes. AB - It has been known for some time that surface integrity has an effect on the fatigue life of metals and "brittle" polymers. In cardiovascular applications of polymeric materials, emphasis is placed on elastomers having extended flexure lifetimes (i.e., fatigue life). The effect of surface integrity on the performance properties of Biomer (Ethicon, Inc, Somerville, NJ) a segmented polyurethane used in many blood contacting devices, is being investigated using uniaxial tensile tests in air at room temperature, and biaxial fatigue tests in deionized water at body temperature. Tensile tests were done using ASTM-D-882: Standard Test Methods for Tensile Properties of Thin Plastic Sheeting. No significant differences were noted in the stress-strain curves for specimens with various surface finishes. Fatigue tests were performed using an apparatus developed to allow for the exposure of thin-sheet polymer specimens to fluid at body temperature, while being biaxially strained. Because no standard test method was available, a test protocol was developed with reference to ASTM-D-671-78: Standard Test Methods for the Flexural Fatigue of Plastics by Constant Amplitude of Force. Stress versus life cycle data for specimens with differing surface finishes are being collected. Results to date suggest fatigue life of thin flexing membranes will decrease with increasing order of surface roughness, and fatigue properties are more sensitive to effects of changes in surface integrity than tensile properties measured by monotonic loading. PMID- 2597566 TI - Effect of storage time on red blood cell membrane permeability to creatinine and uric acid. AB - Although there is considerable evidence that blood storage affects red blood cell viability, deformability, and geometry, available data on the effect of blood storage on solute transport across the red blood cell membrane are highly limited. The authors used a stirred ultrafiltration device, with direct cell-free fluid sampling through a semipermeable ultrafiltration membrane, to obtain accurate data on red blood cell membrane permeability to both creatinine and uric acid. Results for influx and efflux experiments can be adequately explained by a passive transport mechanism. The red blood cell membrane permeability to uric acid increased substantially during storage, whereas trends in creatinine permeability were less clear and suggested possible differences between solute efflux and influx experiments. These results provide important insights into the physical and biochemical changes that occur in the red blood cell membrane during storage and also have important implications for analyses of solute removal in hemodialysis. PMID- 2597567 TI - Mechanical failures of the pneumatic Utah-100 and Jarvik total artificial hearts. A comparative study. AB - Jarvik-5 and Jarvik-7 total artificial hearts (TAHs) and Utah-100 TAHs were fabricated and implanted in calves and sheep. In the Jarvik series, 30.7% had mechanical failures (16.1% catastrophic). In the Utah-100 TAH series, 11.1% had mechanical failures (3.7% catastrophic). Failures were classified as: 1) diaphragm failures; 2) valve-holding ring failures; 3) air-leak failures; and 4) prosthetic valve failures. Marked reduction in mechanical failure for the Utah 100 TAH is attributed to progressive component redesign, material selection, and more stringent quality control criteria. PMID- 2597568 TI - Immune response changes with blood pump use in calves. AB - Device-related bacterial infections are a significant deterrent to the long-term implantation of the total artificial heart (TAH). Device-related infections in the calf are caused by the same spectrum of organisms, over approximately the same time course, as those reported in man. We studied immunologic function in two groups of 3-4 month old, Holstein steer calves; four animals underwent cardiopulmonary bypass (CPB) only and seven calves underwent CPB and TAH implantation. There was a transient rise in total white blood cell counts and a transient fall in the hematocrit following the procedures in each group. Absolute numbers of neutrophils in the TAH group declined to near or below preoperative levels by the end of the 1 month study period. There was a transient increase in chemotactic response of isolated neutrophils to bovine C5a immediately following CPB and increased hydrogen peroxide production on postoperative day 3. Hydrogen peroxide levels were elevated in the TAH animals from postoperative day 14 to the end of the study period. Serum immunoglobulin levels of IgG, IgM, and IgA did not change significantly during the study period in the TAH group. IgG levels were elevated after week 3 in the CPB group. PMID- 2597569 TI - Microbiologic survey of prosthetic blood pumps presterilization and poststerilization and at explant retrieval. AB - Device-associated infection remains a major complication of implanted total artificial hearts (TAH). The possibility of microbes being introduced on the device was investigated by conducting a gross microbial assay, pre- and poststerilization, and following explant retrieval. Culture samples were obtained from the housing, base, and blood-contacting diaphragm of Utah-100 artificial ventricles. Additional samples were obtained from atrial sewing cuffs, outflow grafts, drive lines, and percutaneous leads, along with reference control samples prior to ethylene oxide sterilization (ETO). Culturing was repeated poststerilization and at device explant retrieval. Positive bacterial and fungal cultures were found in 24% of the presterilization samples; in the poststerilization samples, positive cultures were found in 6%. Following device explant retrieval, 84% of the cultures were positive. The reference control samples were positive in a limited number of the poststerilization samples. There was no correspondence of the species of micro-organisms found at the same location for each sampling condition. These data demonstrate that the surfaces of the TAH can become contaminated during fabrication. The presence of microbial activity poststerilization raises the possibility of inadequacy of the ETO protocol used with these devices, or contamination of the surgical field. Hearts at explant retrieval had cultures positive for microbes differing from those identified prior to implantation. This finding suggests that device-associated micro-organism colonization occurs through a source other than manufacturing or surgical contamination. PMID- 2597570 TI - Use of a total right heart bypass model for analyses of abnormal hemodynamics in total artificial heart animals, and the function and regulatory mechanisms of a natural heart. AB - By fixing the function of one ventricle, a total right heart bypass model can clarify the function and regulatory mechanism of the natural heart, and the etiology of abnormal hemodynamics in TAH animals such as increased CVP blood pressure and hepatic congestion. The pulmonary artery of a right heart bypass in a goat was clamped proximally; the pulmonary circulation was thus supplied entirely by the artificial heart and the systemic circulation by the natural heart. This model enabled studies of long-term effects of an artificial right heart on systemic circulation at a right heart output of 80-100 ml/kg/min; the response of the natural left heart to changes in output of the right heart; and the response of the natural left heart and artificial right heart to treadmill exercise. It was found that only slight increase in CVP or no increase in blood pressure was observed during the experiment (112 days); a rapid increase in output of the RAH resulted in an increase in left atrial pressure, stroke volume and output of the left ventricle, and a decrease in its heart rate at rest; and significant increase in both artificial right heart and natural left heart output and heart rates were observed during treadmill exercise, despite the marked decrease in left atrial pressure. The above results suggest that the increase in CVP and blood pressure in total artificial heart animals are not due to factors involving the artificial right heart, and that although left ventricular function acts in accordance with Starling's law at rest, this is no longer true during treadmill exercise. PMID- 2597571 TI - Residence time distributions in artificial ventricles. AB - The time that blood elements remain in an artificial ventricle determines the period during which these blood elements are exposed to damaging factors. We present, for the first time, preliminary studies on the residence time distribution (RTD) of a ventricle as a function of type and orientation of valves (Bjork-Shiley and polyurethane valves). We constructed an open loop mock circulation system which simulates the flow and pressure through the left ventricle, and a drive triggered injection unit which can inject a chemical tracer or radioisotope during one diastolic filling phase. RTD studies were done using a Tc-99m radionuclide tracer and a chemical tracer. A scintillation camera clearly showed the influence of backflow through the artificial heart valves, and the intraventricular washout. Results indicate that 42% of the fluid elements are expelled at the end of the first ventricular beat, i.e., 58% of blood elements stayed behind to experience the second beat; 36% of blood elements expelled in the second beat belonged to those in the first diastole; 17% in the third beat; and 5% in a subsequent number of beats. The RTD was found to vary with the position of the Bjork-Shiley (BS) valves. PMID- 2597572 TI - New crisscross-shaped port design for universal serial pumps. AB - The long range goal is the development of a clinically useful, implantable, skeletal muscle powered cardiac assist device (MCAD). To accomplish this goal, two criteria must be met: good anatomic fit, and antithrombogenicity. Because of the relative locations of the latissimus dorsi (LD) muscle and aorta, there are two possible port arrangements: "crisscrossed" (C design), in which the ports are crossed to anastomotic sites, and "prong" shaped (P design), in which no crossover takes place. The purpose of this paper is to determine which of these designs is best from a fluid dynamic perspective, and hence has the best possibility for low thrombogenicity. Flow visualization (FV) techniques were used during two pumping conditions in a mock loop: worst case (MCAD off) and best case (MCAD driven optimally). Results of the MCAD off tests showed that both designs required immediate actuation (for example, an IABP console). However, FV studies under optimal conditions indicated superiority of the C design, most likely due to kinetic energy-induced rotary motion combined with a minimal interport distance. It is concluded that the C design provides ideal flow dynamics, even in valveless pumps, and also has application to valved devices. PMID- 2597573 TI - Development of a new circulatory assist method with the combined effects of intra aortic balloon pumping and counter pulsation. First report. AB - Current circulatory assist methods, such as intra-aortic balloon pumping (IABP), are not always adequate to save acute circulatory failure patients. Therefore, a stronger, percutaneously accessible method is required. We found that the combination of IABP and CP generated a profound circulatory assist effect, and we have consequently developed a new assist system in this study. A sac type blood pump with a volume of 20 ml and a single port without a valve, was developed for CP. In the mock circulatory test, a 20 ml stroke volume was obtained using a cannula with a 5 mm diameter under the following driving conditions: air pressure = 200/-100 mmHg; S/D = 50%; pulse rate = 100 bpm. In vivo experiments were performed using four mongrel dogs with body weights of 12-20 kg. A cannula for CP was inserted via the brachial artery or subclavian artery into the aortic root. The pump flow (PF), coronary artery flow (CF), renal arterial flow (RF), and aortic pressure (AP) were measured, and the combined effects of IABP and CP were compared with their individual effects. In the most effective case, a marked increase in diastolic AP (60%), cardiac output (40%), and CF (100%) was obtained by the combination of IABP and CP, which produced a remarkable effect compared with the single use of IABP and CP. There was no negative effect on RF by this assist method. As this new circulatory support system has many circulatory assist effects, and is percutaneously accessible, it will be available for clinical use. PMID- 2597574 TI - Transesophageal color Doppler echocardiography during mechanical assist circulation. AB - Information available to determine the optimal timing for separation of patients (pts) from mechanical assist circulation (MAC) is usually limited, due to the difficulty of transfer of patients with heavy MAC systems. To evaluate the clinical efficacy of transesophageal color Doppler echocardiography (TEE) in management of patients during MAC, we examined 37 pts (32, intra-aortic balloon pumping = IABP; 4, left ventricular assist device = LVAD; 1, right VAD = RVAD) by TEE. In the other 3 pts, thoracic aneurysms (AN) (2, dissecting An; 1, true AN) were detected by TEE, which were contraindications to safe introduction of IABPs. In 29 pts on IABPs, 2 pts with LVADs, and in 1 pt with a RVAD, patients were safely weaned from MACs with confirmation of full recovery of cardiac function by TEE. However, repeat introduction of IABP support was needed in 2 pts due to severe residual mitral regurgitation, even after initial success; these became the cause of late multiple organ failure. In one pt with a LVAD, a detrimental right to left shunt through the patent foramen ovale, which resulted in severe desaturation of the arterial blood oxygenation, was detected by TEE. Left main coronary flow was measured by TEE and found to increase by 55% on IABP and by 67% on a LVAD. In conclusion, TEE is the only currently available diagnostic tool for total evaluation of cardiac function in an intensive care unit, which can provide very important information for management of patients on MACs. PMID- 2597575 TI - Percutaneous cardiopulmonary bypass to support angioplasty and valvuloplasty. Technical considerations. AB - To eliminate problems during percutaneous transluminal coronary angioplasties (PTCAs) or valvuloplasties (PV), percutaneous cardiopulmonary bypass (PCPB) was used in 19 high-risk patients (pts) to perform supported PTCA (12 pts, age 40-68) for low EF and/or a large area of risk (L main), and supported PV (7 pts, age 68 92) for "nonoperative" candidates with severe AS. Our experience promoted a review of the technical aspects of PCPB was needed for a successful outcome in these high-risk patients. All patients were treated with IV amnestics while awake in the catheter laboratory. Early in the experience, 20F arterial and venous cannulas were inserted via a 2 cm cutdown in the right groin; now 17F arterial and 20F venous cannulas are placed via a Seldinger technique using fluoroscopy. Traversement of the iliac vein is enhanced by a roll under the buttocks. If the artery is calcified, a cutdown, vessel loops, and direct repair are employed to assure post-PCPB patency. Total flows of 6L/min are easily achieved with nonreservoir centrifugal pump bypass. If flow or pressures fall, 200 cc of blood or crystalloid rapidly improves venous drainage and flows and unlike during reservoir bypass, alpha agonists are only rarely necessary; CaCl often produces nausea in these patients. PCWP's are brought to 0-5 mm Hg. Due to the 1,500 cc priming volume, on-pump transfusion is often required. Two patients were successfully transported to the OR on PCPB for treatment of catheter failures. With attention to technical details, percutaneous bypass supported PTCA or PV is an important new therapy for high risk patients. PMID- 2597576 TI - Anatomic considerations for abdominally placed permanent left ventricular assist devices. AB - To determine anatomic parameters for a permanent, electrically actuated left ventricular assist device (LVAD), the effects of abdominal placement of pneumatic LVADs used as temporary support for patients awaiting heart transplantation was studied. Understanding the anatomic constraints imposed by the abdominal viscera in LVAD placement is crucial, because improper placement can result in compression or obstruction of adjacent structures. Anatomic compatibility was assessed in four men (age 22-48 years) who were supported by the LVAD for over 1 month (range 35-132 days). The pump was intraperitoneally placed in the left upper quadrant. Radiographic techniques were employed, including CT scanning (with patients supine) and contrast imaging (patients in anatomical position), and the pump and conduits appeared to be properly positioned, with minimal compression of the body of the stomach, and no obstruction of adjacent organs. Three patients returned to a solid food diet and exercised daily by stationary cycling and walking. No signs of migration or erosion of the pump were present at the time of LVAD removal and cardiac transplantation. Successful clinical experience with short-term use of the LVAD suggests that the electrically actuated device can be well tolerated in patients requiring permanent left ventricular assistance. PMID- 2597577 TI - The incidence of isolated left ventricular failure in bridge-to-transplant candidates. AB - Twenty-one patients (pts) were supported with mechanical devices as a bridge to cardiac transplantation (Tx). Ventricular function was assessed by a combination of angiography, echocardiography, nuclear scans, hemodynamics, and visual inspection at the time of device insertion. Twelve pts had biventricular failure (BVF) and 11 received biventricular support with extracorporeal membrane oxygenation (two pts), biventricular assist devices (VAD) (eight pts), or an artificial heart (one pt). One BVF pt received a left VAD (LVAD) and drug support for severe right ventricular failure (RVF), which resolved after 48 hr. The remaining nine pts had left ventricular failure (LVF), with only mild to moderate RVF, and received LVADs with minimal drugs. Eleven pts were tx, with nine survivors. A comparison of pts with LVF vs BVF revealed no differences in age, gender, device flows, duration of support, diagnosis, number tx, or number survived. The incidence of LVF was 43% vs 57% BVF in bridge-to-transplant pts. LVAD support alone is often successful in pts with mild or moderate BVF, but is rarely successful in pts with severe BVF. PMID- 2597578 TI - Erythrocyte deformability in patients on left ventricular assist systems. AB - Preliminary hemorheologic studies using clinical filtration techniques on blood cell suspensions have suggested that changes in erythrocyte (RBC) deformability occur during left ventricular assist system (LVAS) support. In the biophysics literature, it is generally accepted that the elastic properties of the RBC membrane complex affect the microcirculatory deformability of the whole cell (cytoplasmic pathologies excepted). This paper compares single cell measurements of the surface shear elastic modulus, mu, of the RBC membrane complex (determined using micropipette aspiration) to available clinical filtration pressure data during Novacor LVAS support, over 33 and 126 days in four patients. PMID- 2597579 TI - A thin-film glucose electrode system with compensation for drift. AB - Thin-film platinum electrodes have been prepared for use in a system for measurement of glucose. Cyclic voltammetry was used to test the electrodes in phosphate and bicarbonate solutions, and in the dialysate of human serum. The peak current output for glucose concentrations between 50-300 mg/dl in a phosphate buffer, and 100-250 mg/dl in the dialysate of human serum, were linear. Two of the three inflection points occurring in the voltammograms are invariant with changes in scan rate, pH, CO2, O2, and glucose. A method for using these points to compensate for voltage drift and current shift is discussed. PMID- 2597580 TI - In vivo determinants of energy consumption in electric motor driven artificial hearts. AB - To identify factors responsible for energy consumption, a retrospective investigation of the in-vivo performance of the 100 ml electric motor-driven left ventricular assist device (ELVAD), and the e-motor 100 ml total artificial heart, was undertaken. Multivariate regression analysis of the device parameters demonstrated that device flow, and estimated outlet pressure, were the most significant independent variables for predicting changes in motor power. Weighted least-square curvefit, using the product of these two variables, showed that changes in energy consumption can be well predicted for the ventricular assist device (r2 = 0.732). However, by applying the same model to the total artificial heart (ETAH), less favorable results were achieved (r2 = 0.422). In this model, device flow seemed to be more important in predicting energy consumption for the ETAH compared to the ELVAD. Therefore, changing the model by using flow to the third order significantly improved the fit (r2 = 0.6706) for the ETAH, and could compensate in part for the greater variability of the values and increased number of outliers in this group. PMID- 2597581 TI - A learning initiative in Scotland. PMID- 2597582 TI - MGDS examination'. PMID- 2597583 TI - 'MDU Report' and 'What is Informed Consent?'. PMID- 2597584 TI - 'Sugar: the autumn issue'. PMID- 2597585 TI - Well hidden sugar'. PMID- 2597587 TI - 'Tooth transplant record?'. PMID- 2597586 TI - 'The capitation study--your questions answered'. PMID- 2597588 TI - Oral surgical instruments. PMID- 2597589 TI - Register of developmental dental anomalies. PMID- 2597590 TI - Health Promotion Authority for Wales. PMID- 2597591 TI - 'Practice visits'. PMID- 2597592 TI - 'The changes in dental caries experience of 12-year-old schoolchildren in two Somerset schools. A review after an interval of 25 years'. PMID- 2597593 TI - Oral medicine in practice: orofacial pain. PMID- 2597594 TI - Resorption of premolar roots by ectopic canines. AB - This case report describes an unusual phenomenon related to bilaterally displaced canines, where both upper lateral incisors were absent, but where the canines produced extensive root resorption of both upper first premolars, necessitating their removal. PMID- 2597595 TI - Nicaragua--dentistry against the odds. AB - In July 1988, Roxana Marisa Orellana, a young dentist, travelled from Nicaragua to study community dental health in the UK. Now, 16 months on, she writes about oral health and the dental service in Nicaragua, outlining some of the problems she and her fellow dentists encountered while at work in the strife-torn Central American country. PMID- 2597596 TI - Implants in dental prosthetics. Part 1. PMID- 2597597 TI - Guard against accidents with syringes and needles. PMID- 2597598 TI - Treatment of hypertension with a fixed ratio combination of long-acting propranolol and bendrofluazide, and influence of age of the subject. AB - The efficacy of sustained-release propranolol 160 mg (Inderal LA), bendrofluazide 5 mg and the combination preparation Inderex (bendrofluazide 5 mg and Inderal LA) in the treatment of hypertension was investigated. Twenty-one patients over a wide age range were studied, as it was of particular interest to find whether differing responses across a range of age groups might exist 24 hours post dosing. Blood pressure control was greater with Inderex than with either Inderal LA or bendrofluazide. No significant difference between different age groups on the three treatments was demonstrated. There was some evidence, not statistically significant, suggesting potassium values to be lower on bendrofluazide and on Inderex. Serum glutamate oxaloacetate transaminase (SGOT) values were raised on bendrofluazide. Inderex is more effective in lowering blood pressure than either bendrofluazide or Inderal LA alone, and as a single capsule given once daily encourages compliance in comparison with combination treatments. PMID- 2597599 TI - Effects of benfluorex in obese patients with metabolic disorders. AB - Fifty obese (BMI = 40.1 +/- 1.5) subjects (21 men and 21 women; average age 38.6 +/- 3.8 years) were prescribed a 600 cal/day diet (carbohydrates 30 g, proteins 60 g, lipids 10 g). Thirty patients were also given benfluorex (three tablets/day) for six months (Group A), whereas the other 20 patients (Group B) were treated with the dietary measures only. Apart from grade II and III obesity, several patients suffered from dyslipidaemia (Group A: n = 10; Group B: n = 7), non-insulin-dependent diabetes mellitus (NIDDM) (Group A: n = 4; Group B: n = 3) or IGT (Group A: n = 8; Group B: n = 6). The usual blood and biochemical tests and clinical examinations were carried out on Days 0, 90 and 180, together with the OGTT and glucagon test to determine blood glucose levels, IRI and CPR. There was no statistical difference between the weight loss of Group A and that of Group B. In Group A there was a statistically significant reduction (p less than 0.001) in total cholesterol, triglycerides, total/HDL-cholesterol and beta/alpha lipoproteins and a significant increase in HDL-cholesterol and alpha-lipoproteins (p less than 0.001), whereas in Group B only a significant reduction in triglycerides (p less than 0.001) was observed. In NIDDM patients treated with benfluorex, normalisation of basal blood glucose levels was accompanied by an improvement in the OGTT blood glucose curve which was statistically significant relative to Group B. Benfluorex was well tolerated by all patients and no adverse event was reported.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2597600 TI - Double-blind clinical trial of nefopam in comparison with pentazocine in surgical patients. AB - A double-blind clinical study comparing a new non-narcotic analgesic, nefopam, with pentazocine was carried out on 50 Indian patients. Forty patients had undergone surgical procedures, and the remaining 10 had musculoskeletal or traumatic disorders. There were 25 patients in each group. It was observed that both drugs were capable of relieving post-surgical pain which was either very severe (score 4) or severe (score 3). Their efficacy was comparable. In patients who had an initial pain score of 4, a significant (p less than 0.05) fall in the sum of pain intensity scores (SPIS) occurred in two days. For an initial pain score of 3, a correspondingly significant fall in SPIS took three days. These results were statistically significant (p less than 0.01). Nefopam had a significantly better side effect profile than pentazocine. In the nefopam group, 4/25 patients had side effects, as opposed to 10/25 in the pentazocine group (p less than 0.05, Fisher's exact probability test). It was also noted that the incidence of side effects was greater in the pentazocine group (61) than the nefopam group (22), the difference being statistically highly significant (p less than 0.001, chi 2-test). A few patients (score 4) in both groups required additional morphine as relief analgesic on the first day of therapy. Thus the non narcotic nefopam is equally effective as the narcotic pentazocine and has less side effects. PMID- 2597601 TI - Comparative study of the efficacy and toxicity of nitrofurantoin and amoxycillin in the treatment of bacteriuria of pregnancy. PMID- 2597603 TI - Thrombophlebitis as the presenting feature of extramedullary spread in multiple myeloma. PMID- 2597602 TI - Neurological complications of heart disease in childhood. AB - A retrospective review was undertaken of 10 years experience in a Regional referral centre for cardiothoracic surgery identified 37 children with cardiovascular disease who developed chronic neurological handicap. In two-thirds of these, neurological lesions occurred in association with cardiovascular surgery, whilst in one-third they were unrelated to surgery. Motor handicap was found in the majority (94 per cent) of cases, with hemiplegia, tetraplegia and paraplegia being the most common patterns. In half the children, motor and intellectual function was severely impaired. Neurological complications of cardiovascular disease account for approximately two per cent of children with cerebral palsy in the area served by our hospital. One per cent of children undergoing cardiopulmonary bypass surgery risk chronic neurological handicap. Potentially avoidable factors could only be identified in a small proportion of cases. PMID- 2597604 TI - Hyperkalaemia exacerbated by amitryptiline following overdose of potassium thiazide combination. PMID- 2597605 TI - Non-tuberculous psoas abscess. PMID- 2597606 TI - An open study to assess the acceptability and effectiveness of miconazole 1,200 mg single ovule in the treatment of acute vaginal candidosis. AB - The efficacy and acceptability of a single dose 'ovule' formulation of miconazole in the treatment of acute vaginal candidosis has been assessed in 42 patients attending a GU clinic. The signs and symptoms of vaginal candidosis were assessed by the investigator at an initial visit, and at seven and 28 days post-treatment. A high vaginal swab was taken at each visit, for routine microbiology. Patients also rated their symptoms daily for seven days post-treatment. The cure rate at Day 7 was approximately 88 per cent, with the recurrence rate at Day 28 estimated as 16 per cent of those cured. All patients found the single dosage formulation easy to use, and the majority thought the ovule effective as a treatment for their vaginal candidosis. PMID- 2597607 TI - Tuberculin testing: comparison of imotest with Heaf and Mantoux. AB - Immunisation against tuberculosis is still recommended for secondary school children in the UK. Only children who do not react to tuberculin tests are offered vaccination. We report the results of two studies, carried out to evaluate a new applicator of the disposable Imotest multiple puncture tuberculin test. The results demonstrate that Imotest is well tolerated and compares favourably with the Heaf and Mantoux tests. Imotest detected significantly more tuberculin responders than Heaf. PMID- 2597608 TI - Pharmacokinetics of mezlocillin in pleural fluid. AB - Mezlocillin concentrations in the pleural fluid and serum of six patients with malignant pleural effusion were determined following administration of 10 g mezlocillin over 30 minutes as a rapid infusion. Thirty minutes and eight hours after the infusion had been completed, concentrations of the active ingredient in the pleural fluid were 36.44 micrograms/ml and 112 micrograms/ml respectively; in the serum the respective values were 777.89 micrograms/ml and 44.22 micrograms/ml. The concentrations of active ingredient in the pleural fluid exceed the MIC for clinically significant pathogenic germs. The elimination half life of mezlocillin in malignant pleural effusion is prolonged. PMID- 2597609 TI - Non-invasive evaluation of the myopathy of coronary artery disease. AB - The application of cross-sectional echocardiography to the evaluation of patients with ischaemic heart diseases has been limited to certain specific situations, such as recognition of generalised ventricular dysfunction and regional wall motion abnormalities. Myocardial perfusion scintigraphy using thallium-201 has been used at rest and after exercise to display perfusion defects. Clinical, echocardiographic data and thallium-201 studies of 36 patients with chronic congestive heart failure and coronary artery disease were analysed to confirm the differential diagnosis of the myopathy of coronary artery disease. Thirty patients (85 per cent) had a history of one or more myocardial infarctions, 22 per cent cardiomegaly, 16 per cent mitral insufficiency and 30 per cent anginal pain. Echocardiographic studies showed global hypokinesia in 40 per cent of patients, aneurysmal dilatation of the left ventricle in 11 per cent, markedly reduced shortening fraction in 40 per cent and increased left ventricular systolic and diastolic dimensions in all the tested cases (100 per cent). All patients displayed perfusion defects, with reverse redistribution defects in 10 cases only (30 per cent) and extensive fixed defects in 26 cases (70 per cent). This study indicates that ischaemic cardiomyopathy is a distinct entity, since it results from multiple infarcts producing multifocal ventricular wall motion abnormalities with reduced left ventricular function. PMID- 2597610 TI - Significance of a high erythrocyte sedimentation rate in general practice. AB - For eight months the erythrocyte sedimentation rate (ESR) was recorded prospectively in patients over 70 years of age to elucidate the prevalence and causes of high ESR in this age group. All patients having an ESR over 40 mm/h were thoroughly investigated. Ninety men and 349 women had their ESR taken. Sixteen men (18 per cent) and 42 women (12 per cent) had an ESR above this level. Eighty-four separate diagnoses were found to contribute to an elevation of the ESR. Twenty-eight patients (40 per cent of those with high ESR) had multiple diagnoses that might have contributed to the high ESR. The most frequent diagnoses were infection, especially chronic bronchitis, rheumatoid arthritis and renal failure. As a result of the study, nine new diagnoses were found and three patients could be offered effective treatment. We conclude that a multifactorial aetiology is common when the ESR is elevated and that a thorough examination is advisable in such cases. However, screening of ESR in elderly patients in general practice has little therapeutic consequence and selective use of the test is preferable. PMID- 2597612 TI - Aminoglutethimide-induced hyperkalaemia. AB - Aminoglutethimide, a drug which inhibits adrenal hormone synthesis, may alleviate pain in metastatic breast carcinoma. A case is reported in which severe hyperkalaemia supervened two years after commencing treatment with aminoglutethimide; a constant dose was used in conjunction with cortisone supplements. This indicates the need for constant biochemical monitoring, or better still, prophylactic administration of fluorohydrocortisone as mineralocortical replacement. This is the first case of aminoglutethimide-induced hyperkalaemia reported, illustrating the rarity of the complication. Adrenal failure due to glucocorticoid deficiency was also present and required an increased dosage of cortisone. Maintenance of glucocorticoid and mineralcorticoid need regular review throughout therapy, to counteract intercurrent stress. PMID- 2597611 TI - Comprehensive care of elderly patients in a surgical/geriatric unit. AB - In Sunderland, acute medical hospital admissions for patients aged 65 and over are cared for primarily by the Consultant Physician in Geriatric Medicine. Many patients have associated surgical problems, and since 1954 these have been investigated and treated in the Surgical/Geriatric wards. This paper examines the type of work encountered and attempts to evaluate the benefits of this combined approach. PMID- 2597613 TI - Post-traumatic parotid sialocoele. AB - A case of post-traumatic parotid sialocoele (subcutaneous collection of parotid secretions) is described. The importance of excluding damage to the parotid gland when facial lacerations are examined is considered. Earlier recognition and awareness of the potential problems associated with parotid injury following facial laceration would reduce the problems associated with late diagnosis. PMID- 2597614 TI - The plasma collection system: a new concept in autotransfusion. AB - We have used the Haemonetics Cell-Saver autotransfusion technique in over 6,500 cases since 1979, salvaging more than 11,000 units of packed red blood cells. Major utilization has been in cardiac, vascular, and orthopedic cases. Coagulopathy associated with hypothermia, shock, multiple transfusions, and the autotransfusion technique, which removes clotting factors and platelets, often necessitated use of fresh-frozen plasma and platelet packs postoperatively to control bleeding and clotting problems. However, this defeats the prevention of disease transmission, transfusion reaction, and autoimmunization. Haemonetics has recently developed a plasma collection system which salvages up to 1,000 cc of platelet-rich plasma. Early experience suggests this technique will not only decrease the incidence of postoperative bleeding but further decrease the use of homologous (bank) blood and components. A step-by-step guide to the plasma collection system is discussed. The plasma collection system augments the present autotransfusion technique that conserves red blood cells, thus making complete autologous blood transfusion a reality. PMID- 2597615 TI - Carotid endarterectomy in community practice: surgeon-specific versus institutional results. AB - The efficacy of carotid endarterectomy in preventing stroke is clearly related to appropriate patient selection and low surgical morbidity and mortality. It has been suggested that since results at some centers are better than nationwide statistics, perhaps the operation should be limited to those institutions. In this paper we present an experience with carotid endarterectomy over the past twelve years. These 566 consecutive cases were performed by two vascular surgeons in a large metropolitan area using thirteen different hospitals ranging from 150 to 500 beds. Our mortality of 0.5% and permanent stroke incidence of 1.6% did not vary significantly from hospital to hospital. Where the results of surgical audits were available from the individual hospitals, the overall complication rates were significantly higher. We conclude that individual surgeons, not institutions, determine the efficacy of carotid endarterectomy in community practice. PMID- 2597616 TI - Carotid artery stump pressure: how reliable is it in predicting the need for a shunt? AB - Carotid artery stump pressure was measured in 84 cases of carotid endarterectomy. The operations were performed in 71 patients over a period of five years. An altered neurological status during temporary occlusion of the carotid artery, assessed with the patient under local anesthesia, was the sole criterion for shunt placement. Stump pressure (SP) was significantly higher in the 69 unshunted cases (mean of 53.3 mmHg) than the 15 shunted cases (mean of 34.2 mmHg). Shunt was required in two of 41 cases (5%) with SP of greater than 50 mmHg, eight of 36 cases (22%) with SP of 25-50 mmHg, five of seven cases (71%) with SP of less than 25 mmHg. The clinical presentation, including history of prior stroke, and the presence of contralateral disease (including complete carotid occlusion), did not influence the need for a shunt. In this series, carotid artery stump pressure has greater predictive value for shunt requirement when it is greater than 50 mmHg or less than 25 mmHg. However, monitoring the neurological status of the patient in the awake state is still the most reliable method of determining shunt requirement. In our experience, this is associated with minimal morbidity and no mortality. PMID- 2597617 TI - Carotid endarterectomy in patients with contralateral carotid occlusion: is the risk increased? AB - Many vascular surgeons believe the risk of carotid endarterectomy is greater if the patient has a contralateral carotid occlusion, and thus believe intraoperative shunting is mandatory. Five hundred and eleven carotid endarterectomies were performed over the last 11 years by two of us (JEM and RAL). Of these, 370 had charts available for detailed analysis. Twenty-seven of these patients had complete occlusion of the contralateral carotid artery. Eight of these 27 patients were asymptomatic and 16 patients had transient ischemic attacks prior to surgery. Two patients had strokes which were stable at the time of surgery. One patient with a previous stroke was operated upon emergently with a new stroke in evolution. All were operated upon under general anesthesia and only three had intraoperative shunting. Occlusion time averaged 17.1 minutes varying from 11 to 34 minutes. There were two deaths, one cardiac and one pulmonary, and no postoperative strokes either temporary or permanent. Of the 343 patients without contralateral occlusion, three patients (.87%) died, and there were 19 (5.5%) neurologic complications of which seven (2%) were present at the time of hospital discharge. It appears that contralateral carotid occlusion does not increase the risk of stroke after carotid endarterectomy even when intraoperative shunting is not used. PMID- 2597618 TI - Perioperative cardiac complications of surgical repair of infrarenal aortic aneurysms. AB - From 1985 to 1987, 261 patients (241 male, 20 female; mean age 66.5 years, range 38-90 years) were hospitalized for elective repair of infrarenal aortic aneurysms. One-hundred forty seven patients (56%) had coronary artery disease, attested to by past history of myocardial infarction or angina pectoris, electrocardiographic signs at rest, or abnormalities of dipyridamole thallium scintigraphy (performed in 72 patients). Ten patients had coronary arteriography and one patient then underwent aortocoronary bypass. Only two patients were not offered operation. All patients operated on had perioperative monitoring using Swan-Ganz catheters. Forty-five patients (17.5%) had a total of 62 postoperative events related to coronary artery disease. These included 40 cases of myocardial ischemia (15%), 16 cases of left heart failure (6%), and six myocardial infarctions (2%). There were nine (3.4%) postoperative deaths, four of which were due to cardiac causes (1.5%). In spite of the frequency of preexisting coronary artery disease and of intra- or postoperative myocardial ischemia, surgical repair of abdominal aortic aneurysm was not responsible for increased perioperative cardiac morbidity or mortality. In this population of aged patients, abdominal aortic aneurysm repair does not necessitate extending the indications for preoperative coronary arteriography or aortocoronary bypass. PMID- 2597620 TI - Blunt arterial injuries associated with multiple trauma. AB - In this retrospective study, we reviewed the records of 62 patients who were treated at a tertiary care community teaching hospital between 1977 and 1987 for major arterial injury caused by blunt trauma. Nearly half (45%, 28/62) of the injuries were to the thoracic aorta, 24% (15/62) were to arteries of the head and neck, 21% (13/62) were to the arteries of the extremities, and 10% (6/62) were to abdominal arteries. Twenty-eight thoracic aortic transections were repaired, 25 with Dacron grafts and three by primary repair. One patient developed an adventitial hematoma in the thoracic aorta, which was evacuated. Two patients required nephrectomies secondary to renal artery injury. Ten patients with internal carotid artery dissection were successfully treated with anticoagulation therapy. Eight (13%) of the 62 patients died: four from exsanguination, one from cardiac tamponade, one from renal failure, one from pulmonary emboli, and one from cerebral infarction secondary to intracerebral edema. Such injuries are amenable to treatment, with patient and end-organ viability, if recognized and treated promptly by the trauma surgeon. PMID- 2597619 TI - Retrograde dissections of the aortic arch after exclusion-bypass of the descending thoracic aorta: a report of three cases. AB - We report three cases of fatal retrograde dissection of the aortic arch after exclusion-bypass with metal clamps according to Carpentier's thromboexclusion method. All three patients were male, aged 59, 66, and 73 years. Initial operative indications were chronic dissections in two cases and atheromatous aneurysm of the descending thoracic aorta in the other. Two of these patients were operated on in an emergency setting for a ruptured aneurysm. In all three cases, an extraanatomic bypass between the ascending aorta and abdominal aorta was performed as the first step: The proximal clamp was then placed distal to the origin of the left subclavian artery. Death occurred two hours, 12 hours, and eight days after operation, respectively. Autopsy revealed retrograde dissection initiating in the aortic arch and reaching the aortic ring as the cause of death. Pathological examination of aortic specimens confirmed that the dissections began just proximal to the site of clamping. To explain this complication, two etiologic factors, occurring either alone or together, have been postulated: postoperative hypertension and trauma to the aortic wall from the clamp. PMID- 2597621 TI - Training of vascular surgeons in France: ten years of the French College of Vascular Surgery. AB - The French College of Vascular Surgeons serves several functions including the organization of vascular surgery training nationwide, overseeing the practical aspects of institutional training, providing motivation for trainees by creating final exams, and bringing surgeons together to update their knowledge. This article details the results of their programs, the demographic changes in vascular surgical practice over the last ten years, and the problems to be solved in the near future. These challenges include: maintenance of autonomy in the surgical world, enlargement of the fields of action, clarification of indications for vascular procedures, demographic control, and recognition of training programs on the wider, European level. PMID- 2597622 TI - Management of suspected mycotic suprarenal aortic aneurysm. AB - Mycotic aortic aneurysm is an uncommonly encountered entity. The diagnosis and management are challenging problems. Involvement of the visceral aorta creates additional problems in management. Experience with a patient having this diagnosis and the dilemma in treatment forms the basis of this report. PMID- 2597623 TI - Intimal fibroplasia: an unusual etiology of stroke. AB - Individuals with arterial intimal fibroplasia represent a rare subset of patients with proliferative disorders of the arterial wall. This case describes the successful antemortem management of intimal fibroplasia of the internal carotid artery which had caused ipsilateral cerebral infarction. The noninvasive and invasive imaging characteristics of the lesion are also described. PMID- 2597624 TI - Congenital arteriovenous malformation of the scalp with high output cardiac failure: a case report. AB - A 19-year-old man was diagnosed with a rapidly enlarging arteriovenous malformation of the scalp and a mild degree of cardiomegaly. Operation to excise the large fistula took place under general anesthesia. Both external carotid arteries and their branches were controlled to prevent intraoperative hemorrhage, and dissection took place down to the periosteum. A split skin graft from the thigh was applied to the scalp defect. The patient recovered well with no further evidence of dyspnea or high output cardiac failure. PMID- 2597625 TI - Primary atherosclerotic aneurysm of the profunda femoris artery associated with distal embolization. AB - A rare case of an isolated atherosclerotic aneurysm of the profunda femoris artery associated with emboli to the distal leg and foot is reported. A mechanism for such distal embolization is proposed and the management of the condition discussed. PMID- 2597626 TI - Semiclosed transfemoral iliac endarterectomy with an oscillating ring stripper. AB - The technique of endarterectomy for the removal of occlusive atherosclerotic lesions of the aorta and iliac arteries has been utilized successfully in the revascularization of ischemic limbs since its introduction in 1951. The oscillating loop endarterectomy device (Amsco-Hall arterial oscillator) has proven to be useful for endarterectomy of segmental occlusive disease as a substitute for bypass with prosthetic graft. For our elderly debilitated patients, we have adopted a new technique of semiclosed transfemoral iliac endarterectomy for management of occlusive external iliac disease with a patent common iliac artery. We report seven patients treated during May 1987 through May 1988 for external iliac artery occlusion by transfemoral oscillating loop endarterectomy. At 12 months for follow-up review, the cumulative limb salvage rate was 80% with no perioperative mortality. One patient required above-knee amputation eight months following endarterectomy to control forefoot sepsis. Two patients required subsequent leg bypass procedures to achieve full healing of foot level amputation. One patient required dilatation of residual stenosis at the iliac bifurcation by percutaneous balloon angioplasty. Semiclosed transfemoral endarterectomy with the Amsco-Hall oscillating loop device remains an attractive option to the vascular surgeon for recanalization of the iliac artery without the need for an extensive retroperitoneal dissection. PMID- 2597627 TI - The predictive relationship between beliefs, attitudes, intentions and secondary school mathematics learning: a theory of reasoned action approach. AB - This study investigated how attitudes and intentions about learning mathematics might be related to subsequent mathematics learning and achievement using the Ajzen and Fishbein theory of reasoned action. The sample consisted of 142 boys and girls between 12 and 14 years old in a large inner city comprehensive school who were assessed in a follow-up design over a nine-month period. Beliefs about the outcomes of learning, attitudes to learning, perceptions of significant others' prescriptions about learning, intentions to engage in learning behaviours, self and teacher reported learning behaviour and mathematics achievement were assessed at both stages. Regression analysis suggested that while the expectancy-value components of attitude did relate to learning behaviour intentions, perceived prescriptions did not relate to intentions. There was a weak relationship between the two measures of learning behaviour, but with neither measure did intention independently predict future behaviour once prior behaviour was taken into account. The best predictor of subsequent mathematics achievement was prior achievement, though teacher-reported learning behaviour did have an independent relationship with subsequent achievement. The findings are discussed in terms of the assessment of learning behaviours, the relevance of the behaviour intention construct for repeated multiple behaviours and future work on how affective variables might be related to cognitive achievements. PMID- 2597628 TI - Pupils' perceptions of school and teachers. I--Identifying the underlying dimensions. AB - Previous comparative studies have shown interesting differences in motivation and approaches to learning between Britain and Hungary, which were considered to reflect different methods of teaching. The present study reports the development of scales designed to measure pupils' perceptions of school and teachers with the intention of relating those perceptions to school motivation and approaches to learning. The scales covered a wide range of aspects relating both to pupils' perceptions of school ethos and aspects of the learning environment. An inventory made up of 18 five-item Likert scales describing perceptions of school and teacher was given to samples of 516 12-15 year-old pupils in five British schools and a comparable sample of 602 pupils in Hungary. The factor structure of the school and teacher perceptions scales was almost identical in the two countries, suggesting that pupils perceive their schools in very similar ways in spite of the contrasting educational and social systems. There were differences between schools which, although small at the scale level, were sometimes large at the level of individual items. It is suggested that a revised set of scales which have been derived from these analyses might be used by schools to judge the way they are perceived by their pupils, and so also by the parents who will be having more influence in future on school policy and management. PMID- 2597629 TI - Pupils' perceptions of school and teachers. II--Relationships with motivation and approaches to learning. AB - The previous article has described the development of scales designed to measure pupils' perceptions of school and teachers. Previous comparative studies have shown interesting differences in motivation and approaches to learning between Britain and Hungary, which were considered to reflect different methods of teaching. This article explores the relationships between a set of inventory scores describing perceptions of school and teachers and another set indicating school motivation and approaches to learning. The complete inventory was given to samples of 516 12-15 year-old pupils in five British schools and a comparable sample of 602 pupils in Hungary. The factor structure of the combined inventory was investigated, together with correlational analyses at scale and item level which suggested that relationships did exist between perceptions of school and teachers, levels of school motivation, and approaches to learning. PMID- 2597630 TI - Cross-validation of short forms of the WISC-R in two British samples. AB - Short forms of the WISC-R were computed by multiple linear regression on two samples of British children aged 6 to 12 years. The predictive validity of each short form was assessed both within the sample on which it was developed and cross-validated on the other sample. The empirically determined loss of power of prediction was found to be less than expected on a priori grounds. Predictions of individual scores at the lower end of the IQ distribution were less acceptable. It is concluded that short forms are robust and of value in research and for screening purposes, but cannot be recommended for clinical purposes. PMID- 2597631 TI - Stratum corneum hydration and amino acid content in xerotic skin. AB - The relationship between clinical severity, the hydration state of the skin surface as assessed by a conductance with a 3.5 MHz high frequency impedance meter, and the amino acid content of the stratum corneum (SC) of six patients with ichthyosis vulgaris and 30 elderly persons with varying degrees of xerosis was investigated. With an increase in the severity of xerosis the SC showed a decrease in hydration and in its extractable amino acid content. There was a significant correlation between the hydration state and amino acid content of the SC. Although there was a significant correlation between the amino acid content of the lower leg SC and that of the forearm SC in the same subject, the former was generally lower, corresponding to the greater incidence of xerosis on the lower leg. These results suggest that a decreased amount of amino acids may be the result of low profilaggrin biosynthesis in the epidermis and that this is involved in the pathogenesis of these xerotic skin conditions. Clinical improvement of the xerosis following treatment with a urea-containing cream was not accompanied by any significant change in the amino acid content of the SC. PMID- 2597632 TI - Large cell anaplastic lymphoma of the skin. AB - Large cell anaplastic lymphoma (LCAL) is a recently described entity recognized by its constant expression of the CD30 antigen and by its morphology. LCAL is classified as high grade malignant lymphoma. We report 10 patients with LCAL of the skin, three with primary LCAL and others in which it developed with cutaneous T-cell lymphoma, mainly mycosis fungoides. The immunophenotype in all but one of these cases, was that of activated T cells. PMID- 2597633 TI - Characterization of skin infiltrating cells in adult T-cell leukaemia/lymphoma (ATLL): clinical, histological and immunohistochemical studies on eight cases. AB - Eight cases of adult T-cell leukaemia/lymphoma (ATLL) with cutaneous involvement were studied. The clinical and histological features of these cases were recorded and immunohistochemistry carried out using a panel of monoclonal antibodies to T cell differentiation antigens. Patients with ATLL showed distinct differences from patients with mycosis fungoides (MF) and Sezary syndrome (SS). Patients tended to have papulonodular and purpuric skin eruptions with pleomorphic lymphoid infiltrates, and often a degree of vasculitis. There was a high level of expression of activated T-cell antigens, CD25, CD30, CD38, T9 and Leu 8. PMID- 2597634 TI - Symptomatic dermographism: wealing, mast cells and histamine are decreased in the skin following long-term application of a potent topical corticosteroid. AB - Clobetasol propionate 0.05% ointment and an otherwise identical steroid-free base were applied topically to a 10 cm2 area on the anterior thighs of six patients with symptomatic dermographism for 6 weeks. Four patients showed a significantly decreased wealing response to stroking of steroid pretreated skin compared to that of control sites. There was a parallel decrease in mast cell numbers and histamine levels in skin biopsies taken from the steroid treated areas. At 6 weeks two patients demonstrated a decrease in flare areas following the intradermal injection of compound 48/80 in steroid pretreated skin compared to base treated sites. Flare areas following intradermal injection of histamine in these two patients were equivalent in base and steroid treated skin. PMID- 2597635 TI - Hydroxyurea in the management of therapy resistant psoriasis. AB - Eighty-five patients with extensive chronic plaque psoriasis, unresponsive to conventional topical therapy, were treated with long-term hydroxyurea in a dose of 0.5-1.5 g daily. Fifty-two (61%) had a satisfactory remission during treatment without significant adverse effects. Treatment was discontinued in 33 patients (39%), due to an inadequate response or significant relapse during treatment and because of adverse reactions (19%). Four (4.7%) patients on hydroxyurea developed actinic psoriasis. Significant haematological abnormalities occurred in 30 patients (35%), but these became normal following a reduction in the dose of hydroxyurea or temporarily stopping the drug. In only six was it considered necessary to discontinue treatment because of bone marrow suppression. Our experience suggests that hydroxyurea is an effective long-term treatment for psoriasis that is refractory to conventional topical therapy and that the incidence of serious adverse effects compares favourably with other cytotoxic drugs. PMID- 2597636 TI - Cutaneous manifestations of cystic fibrosis: possible role of cryoglobulins. AB - A 13-year-old girl with cystic fibrosis (CF), severe lung disease, purpura on the lower extremities and with elevated serum mixed cryoglobulins is described. The possible relationship of the purpura in CF with cryoglobulinaemia is discussed. PMID- 2597637 TI - Isolated lichen planus of the nails associated with primary biliary cirrhosis. AB - Lichen planus is a relatively common inflammatory dermatosis with characteristic lesions affecting the skin, nails and mucous membranes. Nail changes are present in approximately 10% of patients and can occasionally occur in the absence of skin involvement. The association of lichen planus with primary biliary cirrhosis is now well recognized. We report the first case of lichen planus confined to the nails in a patient with primary biliary cirrhosis. PMID- 2597639 TI - Herpetiform and mollusca contagiosa-like cutaneous cryptococcosis in a patient with AIDS. PMID- 2597638 TI - Phospholipid esterified octadeca-9 cis,11 trans-dienoic acid in benign, premalignant and malignant skin lesions. PMID- 2597640 TI - The effect of 'MaxEPA' in the treatment of patients with Behcet's disease. PMID- 2597641 TI - Neutral lipid composition of Fordyce's granules. PMID- 2597642 TI - Caring--is it vital to neuroscience nursing? PMID- 2597643 TI - The reaction of partners and families to significant neurological damage and the need for health team support. AB - The reaction of partners and families to significant neurological damage can be very negative and traumatic. We, as health professionals, need to examine our own attitudes and feelings toward the brain injured and their families and develop a health optimism toward their recovery. We also need to become sensitized to their need for our support, interest and understanding. Certainly, we owe the families our sensitivity, the installation of at least a glimmer of hope, if we expect them to have the courage and motivation to stand by and care for their brain injured loved ones. PMID- 2597644 TI - Mary Glover lecture. Canadian Association of Neuroscience Nurses. June 14, 1989. PMID- 2597645 TI - The construction and assessment of mental maps. AB - In investigations into the manner in which people store spatial information, experimental subjects are often asked to estimate the distances and bearings between various landmarks. Methodology is described for constructing the mental map underlying a subject's matrix of distances, and the mental map underlying a subject's matrix of bearings. Also presented are methods of comparing matrices of distances or bearings, and the mental maps constructed from them, with the geographical map; this enables an assessment of differences between them. Some statistical models of disorientation are considered, and a method of choosing between them is described. PMID- 2597646 TI - Damaged identity and the search for kinship in adult adoptees. AB - A postal questionnaire was sent to 100 members of an organization for helping adopted individuals to trace their origins. Replies were received from 42 women and 34 men, some of whom were interviewed in person or more often by telephone. The voyage of self-discovery was evidently more crucial for women, whose need for a stronger sense of identity had been enhanced by marriage and motherhood. Relatively more men than women had sought help for personal problems in adulthood, although paradoxically more women reported an unhappy experience of adoption and a damaged sense of identity. Predictably, mother-child reunions had often proved disappointing and occasionally distressing for both parties. In contrast, the discovery of lost siblings had usually brought more reward. This aspect of the search for biological relatives deserves more emphasis, in case adoptees (especially when reared as only children and/or when psychologically disturbed) might have more to gain from meeting a sibling than from meeting a parent. PMID- 2597647 TI - Contrasting patterns in the relationship between hypochondriasis and narcissism. AB - This paper investigates the relationship of hypochondriasis to narcissism, starting from the theoretical exposition of hypochondriasis as a disorder, which mainly results from a pervasive sense of 'inner badness' and the associated mistrust in one's own worth, and in bodily worth in particular. Narcissistic personality organization is regarded as one of the modes of adjustment to the primary and 'undifferentiated' hypochondriacal experiences, and aspects of narcissistic development are described along the contrasting patterns that lead to clinical hypochondriasis. The main differences between the patterns can be found in the features and the outcome of the premorbid (pre-hypochondriacal) narcissistic functioning, presence of the accompanying emotional disturbances (anxiety, dysphoria, anger), and the 'purposive background' of hypochondriasis in relation to the narcissistic personality organization. PMID- 2597648 TI - 'Psychosomatic personality'--a personality constellation or an illness-related reaction? AB - Personality-specific features as opposed to illness-related reactions were studied in 101 patients with ulcerative colitis, duodenal ulcers or irritable colon syndrome (experimental group) and 81 patients with gallstone disease, inguinal hernia or varicose veins (control group). The method used was the Lazare Klerman-Armor personality test. Results indicated that features previously suggested to characterize the experimental group, such as egocentricity and dependency, were likely to be illness-related reactions expressed by all patients with an acute disease. The greatest difference between the groups was found on emotionality: the control group found it difficult to control their emotions when they were ill while the experimental group felt emotionally more stable when they were ill. PMID- 2597649 TI - Supernatural impotence: historical review with anthropological and clinical implications. AB - The historical and cultural background of the belief in supernatural impotence is presented, emphasizing its possible implications for clinical practice. A brief historical survey of the concept in Judaism and Christianity is followed by a short anthropological survey of supernatural impotence in different ethnic subcultures in Israel. A case demonstration exemplifies the connection between understanding the patient's cultural background and beliefs and the clinical competence of the therapist. The relationship between the clinical-therapeutic process in psychiatric practice and knowledge of the patient's cultural background and beliefs is stressed. PMID- 2597650 TI - Strategies for coping with infertility. AB - Cognitive models of coping point to the use by individuals of appraisal-focused, problem-focused and emotion-focused coping, as well as the need to consider an individual's coping response in terms of their intrapersonal and interpersonal resources. This cognitive approach was applied to organizing findings from research into the experience of infertility. At least nine coping strategies are identified that can be employed by couples. Discussion also raises several research questions about the personal crisis of infertility that need to be further investigated. PMID- 2597651 TI - Content specific information processing and persecutory delusions: an investigation using the emotional Stroop test. AB - Attentional bias was investigated in patients suffering from persecutory delusions and matched psychiatric and normal controls, using the emotional Stroop task. Subjects were required to colour name words which were either meaningless strings of Os, neutral words, words indicating negative affect, or words judged to be of paranoid content. In comparison with the control subjects the deluded patients demonstrated a selective increase of response time for the paranoid words. A second analysis using indices of interference produced even more marked results. The relevance of these findings for the understanding of delusional thinking is discussed. PMID- 2597652 TI - Gaze and eye-contact with anorexic adolescents. AB - Interviews with seven anorexic female adolescents and 12 control subjects were videotaped for analysis of visual behaviour. Individual looking and mutual gaze of subject and interviewer were coded by two judges and recorded through a two channel push-button system of time recording for 10 min of interview segments. The results indicated that anorexics looked toward the eyes of the interviewer less frequently and more briefly than controls, and that mutual gazing was less common. PMID- 2597653 TI - Repressive coping style and anxiety in stressful dental surgery. AB - Elevated state-anxiety prior to oral surgery is common and is associated with increased post-operative pain. This paper presents a psychological model of predicting elevated anxiety prior to dental surgery. Elevated anxiety and intraoperative stress can be predicted by measuring trait-anxiety. However, prediction may be improved by using a situationally specific measure of trait anxiety, and by taking the patient's coping style into account. Thirty-nine patients undergoing wisdom-tooth extraction took part in the study. The Corah Dental Anxiety Scale was a better predictor of pre-operative anxiety than the STAI trait-anxiety scale. Coping style was measured by means of the Marlowe Crowne Social Desirability Scale in conjunction with scores on trait-anxiety to define three coping style groups: sensitizers (high-anxious), truly low-anxious, and repressors who verbally deny anxiety. Two oral surgeons rated patient intra operative state on 100 mm visual analogue scales. These ratings indicate that 'repressors' exhibit significantly more stress responses than the truly low anxious group, in spite of similar (low) trait-anxiety scores. It is concluded that a situationally specific measure of trait-anxiety is the most appropriate predictor of differential state-anxiety elevations prior to oral surgery. Repressive coping style may be a confounding factor, in terms of predicting elevated anxiety, since some people verbally deny being anxious but express it behaviourally. PMID- 2597654 TI - Covert psychiatric disturbance in patients with globus pharyngis. AB - There is currently little agreement concerning the aetiology of globus pharyngis (nee hystericus), and both physical and psychological factors have been suggested as primary causes of this common disorder. Using validated research questionnaires we tested the hypothesis that there is significant psychiatric morbidity in female globus patients but not in males. One hundred and twenty-one globus patients (90F, 31M) were tested on the Crown-Crisp Experiential Index (CCEI), the General Health Questionnaire (GHQ), the Hysteroid Obsessoid Questionnaire (HOQ) and the Eysenck Personality Questionnaire (EPQ). Female globus patients, but not males, have low extraversion scores and high GHQ scores when compared with age- and sex-matched ENT patient controls, and high mean levels of anxiety, depression and somatic concern on the CCEI. In females the mean total CCEI score was not significantly different from the mean of a psychiatric out-patient group. The males had total CCEI scores similar to a group with no psychiatric symptoms. Globus patients did not have hysteroid traits. We conclude that a substantial minority of globus patients has significant psychiatric morbidity. It is important to exclude mild, reactive-type depression and conversion disorder in these patients, in whom invasive physical investigations are inappropriate. PMID- 2597655 TI - A comparative clinical study of Pierre Robin syndrome and isolated cleft palate. AB - Thirty seven infants with Pierre Robin syndrome were compared with children who had isolated cleft palate. A female preponderance was seen in both groups. Skeletal II jaw relation was observed in 32% of the children with isolated cleft palate. Associated malformations such as hypertelorism and strabismus were more common in infants with Pierre Robin syndrome and also in those with isolated cleft palate combined with a skeletal II jaw relationship when compared with infants who had cleft palate with a skeletal I jaw relationship. The frequency of hypodontia also was greater in the former two groups than in the latter. Furthermore, no difference was found in the frequencies of U- and V-shaped clefts. The frequencies of near relatives with clefts were also not different between groups. Whilst it may be possible to observe from these findings an association between Pierre Robin syndrome and isolated cleft palate, it is difficult to conclude that they support any of the postulates regarding the aetiology of Pierre Robin syndrome. PMID- 2597656 TI - Preserving the great auricular nerve in parotid surgery. AB - This study compares the sensory morbidity associated with preservation of the posterior branch of the great auricular nerve and sacrifice of the nerve during routine parotid surgery. Twelve patients were divided into two groups. Half the patients had the posterior branch of the great auricular nerve preserved and the other half had the nerve sacrificed in the standard manner. Sensory testing was carried out at 3 monthly intervals for 1 year. The results showed significantly less sensory loss to the skin of the ear and the angle of the mandible in those patients where the nerve was preserved. PMID- 2597657 TI - Bone-plates and screws of bioabsorbable poly (L-lactide)--an animal pilot study. AB - Poly (L-lactide), a polymer of lactic acid (PLLA), with an extremely high molecular weight (Mv up to 1 x 10(6] has been synthesised under strictly controlled conditions resulting in a new microporous material with excellent mechanical properties. Bone-plates and screws machined from PLLA were used for fixation of two artificial mandibular fractures in sheep effected by a specially designed bone clamp. Fracture healing was uneventful without visible callus formation. Plates and screws of PLLA gave good stability over a sufficiently long period to enable normal fracture healing. Application in humans seems to be justified. PMID- 2597658 TI - The effect of dexamethasone on neurapraxia following third molar surgery. AB - A double blind, controlled trial was undertaken to assess the effect of intra muscular dexamethasone on neurapraxia following the surgical removal of mandibular third molars. No significant difference was found 24 h post operatively between a control group and a group given dexamethasone. PMID- 2597659 TI - Carotico-cavernous fistula presenting as a late complication of facial trauma. AB - A case of carotico-cavernous fistula following facial trauma is reported. Clinical details of the case are described together with a review of the literature. Aetiology and treatment of the condition are discussed. Carotico cavernous fistula is a rare complication of facial trauma. The case reported is important because the complication presented as a late event some 9 weeks after the initial trauma. PMID- 2597660 TI - Surgical access to bilateral coronoid hyperplasia using the bicoronal flap. AB - The use of the bicoronal flap in the surgical treatment of a case of bilateral coronoid hyperplasia is presented. The surgical approach to large lesions of the coronoid process is discussed. PMID- 2597662 TI - Neurilemmoma of the mandible. Report of a case. AB - A case of neurilemmoma is described recurring 15 years after a previous excision. PMID- 2597661 TI - Neurilemmoma involving the maxillary sinus: a case report. AB - A case is reported of a neurilemmoma arising from the maxillary sinus. Its aetiology, presentation, histology and treatment are discussed. PMID- 2597663 TI - Analgesics and third molar removal. PMID- 2597664 TI - Metabolism of thromboxane B2 in the isolated perfused rat kidney: mass spectrometric identification of urinary products. AB - The metabolism of thromboxane B2 (TXB2), the stable breakdown product of thromboxane A2, has been studied in isolated perfused kidney preparations using a recirculating system. In a first experiment, TXB2 was infused at a rate of 20 micrograms/kg per min. In a second experiment, a 1:1 mixture of TXB2 and octadeuterated TXB2 (0.4 microgram/kg per min each) was infused. Urinary samples collected during the infusion of TXB2 or vehicle were extracted on C18 cartridges and derivatized to methyl or pentafluorobenzyl ester, methyloxime, trimethylsilyl ether. Samples were analyzed by high-resolution gas chromatography-mass spectrometry in the electron impact and negative ion chemical ionization modes. Products of beta-oxidation, reduction of the delta 5,6 double bond and dehydrogenation at C-11 (2,3-dinor-TXB2, 2,3-dinor-TXB1, 2,3,4,5-tetranor-TXB1 and 11-dehydro-TXB2) were identified in addition to unmetabolized TXB2. 2,3,4,5 tetranor-TXB1 and 2,3-dinor-TXB1 were the most abundant metabolites. PMID- 2597665 TI - An appraisal of the role of biliary phospholipases in the pathogenesis of gallstone disease. AB - Human bile contains proteins that influence nucleation of cholesterol. Recently, it has been suggested that activity of phospholipases in bile may play a role in this process. To study the influence of phospholipase on nucleation we have determined the effect of phospholipases A2, C and D on the nucleation time of model bile. Phospholipase C decreased the nucleation time, whereas phospholipase A2 inhibited nucleation. The phospholipases were effective only at relatively high concentrations. Phospholipase D was strongly inhibited in model bile and probably only influenced the nucleation time by an aspecific protein effect. The cleavage products of the different phospholipases were determined in native bile samples of 14 cholesterol gallstone patients, 6 patients without stones and 4 patients with pigment stones. In all samples, choline, phosphorylcholine and free fatty acids (FFA) could be detected. However, there was no significant difference between the three groups of patients. The rate of production of choline, phosphorylcholine and FFA was measured in bile incubated at 37 degrees C. Again, there was no significant difference between the three groups of patients. We conclude that phospholipase activity in bile does not play an important role in the pathogenesis of gallstone disease. PMID- 2597666 TI - Binding of divalent and trivalent cations with crotoxin and with its phospholipase and its non-catalytic subunits: effects on enzymatic activity and on the interaction of phospholipase component with phospholipids. AB - We have studied the interaction of divalent and trivalent with a potent phospholipase A(2) neurotoxin, crotoxin, from Crotalus durissus terrificus venom. The pharmacological action of crotoxin requires dissociation of its catalytic subunit (component B) and of its non-enzymatic chaperone subunit (component A), then the binding of the phospholipase subunit to target sites on cellular membranes and finally phospholipid hydrolysis. In this report, we show that the phospholipase A(2) activity of crotoxin and of component B required Ca2+ and that other divalent cations (Sr2+, Cd2+ and Ba2+) and trivalent lanthanide ions are inhibitors. The lowest phospholipase A(2) activity was observed in the presence of Ba2+, which proved to be a competitive inhibitor of Ca2+. The binding of divalent cations and trivalent lanthanide ions to crotoxin and to its subunits has been examined by equilibrium dialysis and by spectrofluorimetric methods. We found that crotoxin binds two divalent cations per mole with different affinities; the site presenting the highest affinity (K(d) in the mM range) in involved in the activation (or inhibition) of the phospholipase A(2) activity and must therefore be located on component B, the other site (K(d) higher than 10 mM) is probably localized on component A and does not play any role in the catalytic activity of crotoxin. We also observed that crotoxin component B binds to vesicular and micellar phospholipids, even in the absence of divalent cations. The affinity of this interaction either does not change or else increases by an order of magnitude in the presence of divalent cations. PMID- 2597667 TI - Effect of cholesterol on membrane microheterogeneity: a study using 1,6-diphenyl 1,3,5-hexatriene fluorescence lifetime distributions. AB - The effect of cholesterol on microheterogeneity of liposomes obtained from saturated and unsaturated phospholipids was studied by measuring the fluorescence decay of 1,6-diphenyl-1,3,5-hexatriene (DPH). Data obtained by frequency domain fluorometry have been analyzed either by discrete exponential or continuous lifetime distribution approaches. In egg phosphatidylcholine liposomes, the addition of cholesterol increases the lifetime value or the centre of the lifetime distribution. At high cholesterol concentration, good fits are obtained using a monomodal distribution analysis or single exponential component. At low cholesterol concentration an additional short component of low fractional intensity must be included to obtain a good fit. In dipalmitoylphosphatidylcholine, the addition of cholesterol decreases the long lifetime component centre value both in the gel and in the liquid-crystalline state. The DPH lifetime value is sensitive to the dielectric constant of the probe microenvironment, and cholesterol has been shown to modify water penetration in the bilayer. Using this information our data indicate that cholesterol affects the polarity of the microenvironment in liposomes of unsaturated phosphatidylcholine and saturated phosphatidylcholine in different ways. Although the major conclusions of this paper are obtained using changes of the distribution centre upon cholesterol addition, there are also preliminary indications that the lifetime distribution width decreases as cholesterol is added. We have interpreted this observation as being due to the homogenizing effect of cholesterol. PMID- 2597668 TI - Purification of lysophosphatidylcholine transacylase from bovine heart muscle microsomes and regulation of activity by lipids and coenzyme A. AB - Heart muscle microsomes catalyze the transacylation of lysophosphatidylcholine (lyso PC) to produce phosphatidylcholine (PC). The enzyme which catalyzes this reaction, lyso PC:lyso PC transacylase, has been isolated and characterized from bovine heart muscle microsomes. The purification of the enzyme was achieved by a procedure involving extraction with 3-[3-cholamidopropyl)dimethylammonio)-1 propanesulfonate (CHAPS) detergent and chromatography on DEAE-cellulose, Reactive blue agarose, and Matrex gel green A. The purified enzyme was nearly homogeneous and consisted of a single molecular species of 128 kDa as determined by polyacrylamide gel electrophoresis in the presence of dodecyl sulfate. The catalytic activity of the enzyme was dependent on the presence of either CoA or acyl-CoA, both of which maximally stimulated at concentrations of approx. 10 microM. Analysis of the PC produced in the reaction showed that the enzyme catalyzed a transacylation in which both acyl groups arose from lyso PC. Furthermore, the enzyme did not possess acyl-CoA:lyso PC acyltransferase activity, lysophospholipase or acyl-CoA hydrolase activity, nor did it catalyze transacylation from lyso PC to lysophosphatidylethanolamine, lysophosphatidylinositol or lysophosphatidylserine. Although transacylation was highly specific for lyso PC as the substrate, various unsaturated fatty acyl-CoA derivatives served as activators. Palmitoyl-CoA and stearoyl-CoA did not significantly activate, although acetyl-CoA was an effective activator. Further modulation of activity was produced by palmitic acid and PC, both of which further activated the enzyme in the presence of oleoyl-CoA, whereas arachidonic acid, oleic acid, phosphatidylethanolamine and phosphatidylserine had no effect on activity. The high activity of this transacylase and its regulation by lipids suggests an important role for disaturated PC species in membranes and a mechanism for controlling the metabolism of lyso PC. PMID- 2597669 TI - Induction of microsomal 1-acylglycerophosphocholine acyltransferase by peroxisome proliferators in rat kidney; co-induction with peroxisomal beta-oxidation. AB - Induction of microsomal 1-acyl-glycerophosphocholine (GPC) acyltransferase in rat tissues by four peroxisome proliferators, clofibric acid, tiadenol, DEHP and PFOA, was examined. Among the nine tissues examined, kidney, liver and intestinal mucosa responded to the challenges by the peroxisome proliferators to induce the enzyme. The treatment of rats with various dose of clofibric acid, tiadenol, DEHP or PFOA resulted in an induction of kidney microsomal 1-acyl-GPC acyltransferase in a dose-dependent manner. Despite the structural dissimilarity of peroxisome proliferators, the induction of microsomal 1-acyl-GPC acyltransferase was highly correlated with the induction of peroxisomal beta-oxidation. The activity of microsomal 1-acyl-GPC acyltransferase was not affected by changes in hormonal (adrenalectomy, diabetes, hyperthyroidism and hypothyroidism) and nutritional (starvation, starvation-refeeding, fat-free-diet feeding and high-fat-diet feeding) states. The induction of renal microsomal 1-acyl-GPC acyltransferase was seen in mice subsequent to the administration of clofibric acid and tiadenol and in guinea pigs subsequent to the administration of tiadenol. These results may indicate that kidney microsomal 1-acyl-GPC acyltransferase is a highly specific parameter responsive to the challenges by peroxisome proliferators and may suggest that the possibility that the inductions by peroxisome proliferators of microsomal 1-acyl-GPC acyltransferase and peroxisomal beta-oxidation in kidney are co-regulated. PMID- 2597670 TI - Surfactant peptides stimulate uptake of phosphatidylcholine by isolated cells. AB - To determine whether small hydrophobic surfactant peptides (SP-B and SP-C) participate in recycling of pulmonary surfactant phospholipid, we determined the effect of these peptides on transfer of 3H- or 14C-labelled phosphatidylcholine from liposomes to isolated rat alveolar Type II cells and Chinese hamster lung fibroblasts. Both natural and synthetic SP-B and SP-C markedly stimulated phosphatidylcholine transfer to alveolar Type II cells and Chinese hamster lung fibroblasts in a dose- and time-dependent fashion. Effects of the peptides on phospholipid uptake were dose-dependent, but not saturable and occurred at both 4 and 37 degrees C. Uptake of labelled phospholipid into a lamellar body fraction prepared from Type II cells was augmented in the presence of SP-B. Neither SP-B nor SP-C augmented exchange of labelled plasma membrane phosphatidylcholine from isolated Type II cells or enhanced the release of surfactant phospholipid when compared to liposomes without SP-B or SP-C. Addition of native bovine SP-B and SP C to the phospholipid vesicles perturbed the size and structure of the vesicles as determined by electron microscopy. To determine the structural elements responsible for the effect of the peptides on phospholipid uptake, fragments of SP-B were synthesized by solid-phase protein synthesis and their effects on phospholipid uptake assessed in Type II epithelial cells. SP-B (1-60) stimulated phospholipid uptake 7-fold. A smaller fragment of SP-B (15-60) was less active and the SP-B peptide (40-60) failed to augment phospholipid uptake significantly. Like SP-B and SP-C, surfactant-associated protein (SP-A) enhanced phospholipid uptake by Type II cells. However, SP-A failed to significantly stimulate phosphatidylcholine uptake by Chinese hamster lung fibroblasts. These studies demonstrate the independent activity of surfactant proteins SP-B and SP-C on the uptake of phospholipid by Type II epithelial cells and Chinese hamster lung fibroblasts in vitro. PMID- 2597671 TI - O-alkyl-O-methylglycerophosphocholine, an antineoplastic lipid, undergoes spontaneous redistribution between biological membranes prepared from HL-60 cells. AB - Cytotoxic actions of the unnatural phospholipid 1-O-alkyl-2-O-methyl-sn-glycero-3 phosphocholine (alkylmethyl-GPC) appear to be targeted to the plasma membrane of sensitive cells. We analyzed the distribution of [3H]alkylmethoxy-GPC in subcellular membranes isolated from human promyelocytic leukemia (HL-60) cells. [3H]Alkylmethyl-GPC added to intact cells selectively labels plasma membrane enriched fractions of the postnuclear supernatant, but the labeling profile is independent of the temperature and duration of the incubation, and concentration of the molecule. Also, an identical distribution pattern is obtained when [3H]alkylmethyl-GPC is directly added to postnuclear supernatants. Moreover, [3H]alkylmethyl-GPC translocates between subcellular membranes in a manner that does not depend on membrane-adsorbed or cytosolic transfer proteins. These results indicate that the subcellular localization studies reported for alkylmethyl-GPC and structurally-related molecules must be interpreted with caution. PMID- 2597672 TI - Oligomers of prostaglandin B1 inhibit in vitro phospholipase A2 activity. AB - Oligomers of prostaglandin B1 inhibited phospholipase A2 extracted from human neutrophils in a dose-dependent manner (IC50 = 5 microM), while the monomer was not inhibitory at concentrations of 10 microM or less. The inhibitory activity of PGB1 oligomers increased with increasing polymer size; PGB dimer had approximately one-half the maximal inhibitory activity of PGBx, while a trimer was almost as inhibitory as a tetramer and PGBx (n = 6). PGBx as an oil or as a water-soluble sodium-salt-inhibited Ca2(+)-dependent phospholipase A2 from snake venom, bovine pancreas, human neutrophil and platelet, human synovial fluid, and human sperm with IC50 values ranging from 0.5-7.5 microM. Inhibition was independent of added Ca2+ and was independent of substrate phospholipid concentration. Interaction of purified snake venom phospholipase A2 (Naja mocambique) with PGBx resulted in dose-dependent quenching of the enzyme's tryptophan fluorescence; 50% quench was noted with a molar ratio of PGBx/enzyme of 1.5. Inhibition of phospholipase A2 activity by PGBx was relieved in a dose dependent manner by either defatted or untreated bovine serum albumin. PGBx is a potent in vitro inhibitor of a wide spectrum of phospholipases A2, and as illustrated in the accompanying paper, has profound inhibitory effects on arachidonic acid mobilization in human neutrophils and vascular endothelial cells. Modulation of cellular and extracellular phospholipases A2, and the bioactive transmitters generated by this catalytic event, may be a basic mechanism by which oligomers of prostaglandin B1 exert their reported membrane protective effects. PMID- 2597673 TI - Proton nuclear magnetic resonance methyl and methylene linewidths from plasma decrease during postprandial lipemia. AB - Narrow proton nuclear magnetic resonance (1H-NMR) linewidths from plasma have been associated with the presence of malignancy (Fossel et al., New Engl. J. Med. (1986) 315, 1369-1376). In that study, subjects and controls were not fasted. In the present study, 1H-NMR methyl and methylene linewidths were measured in plasma from normolipemic individuals without cancer both during fasting and every 90 min after eating a fat meal. Plasma lipoprotein levels were measured in order to relate results to postprandial lipemia. Methyl, methylene, and average 1H-NMR linewidths were strongly positively correlated with high-density lipoprotein levels and inversely correlated with triacylglycerol-rich lipoprotein levels in both the fasting and postprandial states. Linewidths decreased postprandially, reaching a nadir at the peak of plasma triacylglycerol levels. This study demonstrated that postprandial lipemia can lead to narrowing of plasma methyl and methylene resonances comparable to that reported for subjects with cancer. PMID- 2597674 TI - Discoidal complexes containing apolipoprotein E and their transformation by lecithin-cholesterol acyltransferase. AB - The primary objectives of this study were to determine whether analogs to native discoidal apolipoprotein (apo)E-containing high-density lipoproteins (HDL) could be prepared in vitro, and if so, whether their conversion by lecithin-cholesterol acyltransferase (LCAT; EC 2.3.1.43) produced particles with properties comparable to those of core-containing, spherical, apoE-containing HDL in human plasma. Complexes composed of apoE and POPC, without and with incorporated unesterified cholesterol, were prepared by the cholate-dialysis technique. Gradient gel electrophoresis showed that these preparations contain discrete species both within (14-40 nm) and outside (10.8-14 nm) the size range of discoidal apoE containing HDL reported in LCAT deficiency. The isolated complexes were discoidal particles whose size directly correlated with their POPC:apoE molar ratio: increasing this ratio resulted in an increase in larger complexes and a reduction in smaller ones. At all POPC:apoE molar ratios, size profiles included a major peak corresponding to a discoidal complex 14.4 nm long. Preparations with POPC:apoE molar ratios greater than 150:1 contained two distinct groups of complexes, also in the size range of discoidal apoE-containing HDL from patients with LCAT deficiency. Incorporation of unesterified cholesterol into preparations (molar ratio of 0.5:1, unesterified cholesterol:POPC) resulted in component profiles exhibiting a major peak corresponding to a discoidal complex 10.9 nm long. An increase of unesterified cholesterol and POPC (at the 0.5:1 molar ratio) in the initial mixture, increased the proportion of larger complexes in the profile. Incubation of isolated POPC-apoE discoidal complexes (mean sizes, 14.4 and 23.9 nm) with purified LCAT and a source of unesterified cholesterol converted the complexes to spherical, cholesteryl ester-containing products with mean diameters of 11.1 nm and 14.0 nm, corresponding to apoE-containing HDL found in normal plasma. Conversion of smaller cholesterol-containing discoidal complexes (mean size, 10.9 nm) under identical conditions resulted in spherical products 11.3, 13.3, and 14.7 nm across. The mean sizes of these conversion products compared favorably with those (mean diameter, 12.3 nm) of apoE containing HDL of human plasma. This conversion of cholesterol-containing complexes is accompanied by a shift of some apoE to the LDL particle size interval. Our study indicates that apoE-containing complexes formed by the cholate-dialysis method include species similar to discoidal apoE-containing HDL and that incubation with LCAT converts most of them to spherical core-containing particles in the size range of plasma apoE-containing HDL. Plasma HDL particles containing apoE may arise in part from direct conversion of discoidal apoE containing HDL by LCAT. PMID- 2597676 TI - Isolation and characterisation of a 167 bp core particle isolated from stripped chicken erythrocyte chromatin. AB - We have digested chicken erythrocyte soluble chromatin, both unstripped and stripped of histones H1 and H5 with either 0.6 M NaCl or DNA-cellulose, with micrococcal nuclease (MNase). Digestion of unstripped chromatin to monomeric particles initially paused at 188 bp DNA; continued digestion resulted in another pause at 177 before the 167 bp chromatosome and 146 bp core particle were obtained. Digestion of stripped chromatin to monomeric particles paused transiently at 177 bp; continued digestion resulted in marked pauses at 167 and 156 before the 146 bp core particle was obtained. These results suggested that 167 bp DNA representing two complete turns are bound to the histone octamer. Histone H1/H5 binds an additional two helical turns of DNA, thereby protecting up to 188 bp DNA against nuclease digestion. Monomeric particles containing 167 bp DNA were isolated from stripped chromatin and found by DNase I digestion to be a homogeneous population with a 10 bp DNA extension to either end relative to the 146 bp core particle. Thermal denaturation and circular dichroism spectroscopy showed stronger histone-DNA interactions and increased DNA winding as the length of DNA attached to the core histone octamer was decreased. Thermal denaturation also showed three classes of histone-DNA interaction: the core particle containing 167 bp DNA had tight binding of ten helical turns of DNA, intermediate binding of two helical turns and looser binding of four helical turns. PMID- 2597675 TI - Structure of the low-density lipoprotein receptor-related protein (LRP) promoter. AB - The low-density Lipoprotein receptor-related protein (LRP) is a 4544-amino-acid membrane protein which closely resembles the LDL receptor in its arrangement of cysteine-rich motifs. Binding studies have suggested that one function of the molecule is as a receptor for ligands containing apolipoprotein E. We present here the sequence and structure of the promoter region of the LRP. These data show that the LRP contains no sterol regulatory element, and is not down regulated by sterols like the LDL receptor. This lends further support to the identity of the LRP as a chylomicron remnant receptor. PMID- 2597677 TI - Nucleoids, a subnuclear system capable of chain elongation. AB - Nucleoids, prepared by salt extraction of non-DNase-digested nuclei, have properties similar, but not identical, to those of nuclear matrices which are prepared by salt extraction of DNase-digested nuclei. Nuclear matrices retained less pulse-labelled DNA, slightly less bound DNA polymerase alpha and DNA primase, but had greater in vitro DNA synthesis and in vitro priming. Nucleoids contained larger (110 S) DNA chains than nuclear matrices (30 S). Each type of residual nuclear structure could synthesize 4.5 S Okazaki fragments. When extracted with increasing concentrations of salt, DNase-digested nucleo lost the ability for further elongation of the 4.5 S DNA intermediate after 0.1-0.2 M NaCl, whereas undigested nuclei retained this ability up to 0.9 M NaCl. Chain elongation to 28 S DNA chains could be restored to nucleoids, but not to nuclear matrices, by the addition of nuclear extracts. PMID- 2597679 TI - Nucleotide sequence of the EcoRII restriction endonuclease gene. AB - The nucleotide sequence of a 1394 basepair (bp) DNA fragment containing the EcoRII restriction endonuclease (R.EcoRII) gene was determined. The endonuclease gene is 1206 bp in length (predicted 402 amino acids (aa) and Mr = 45 178) and is separated by 33 bp from the EcoRII modification methylase (M.EcoRII) gene. The EcoRII restriction-modification system has a tail-to-tail organization of the two genes. PMID- 2597678 TI - Nucleotide composition bias and CpG dinucleotide content in the genomes of HIV and HTLV 1/2. AB - Nucleotide compositions of the HIV subfamily and HTLV 1/2 genomes are strongly biased in a remarkably opposite way; HIV is adenine-rich and cytosine-poor while HTLV 1/2 is cytosine-rich and adenine-poor. In addition, the CpG dinucleotides are underrepresented in HIV but abundant in HTLV 1/2. By these two properties the genomes of HIV and HTLV 1/2 mimic an (A + T)-rich and (G + C)-rich segment of the host genome, respectively. These dramatic differences between the two human retroviruses might have evolved to direct integration of the retroviral genomes into specific segments of the human chromosomes. PMID- 2597680 TI - Identification of a human ribosomal protein mRNA with increased expression in colorectal tumours. AB - A human ribosomal protein cDNA was selected from a normal colon cDNA library on the basis of overexpression in familial adenomatous polyposis. Nucleotide sequence analysis was used to identify this cDNA as corresponding to the human equivalent of the rat ribosomal protein L31 (HL31). We have quantified the expression of HL31 mRNA in colorectal tumours and found overexpression in 23 out of 23 cases. Our results indicate that HL31 is associated with a malfunction of normal growth regulatory mechanisms in these tumours, and suggest a role for HL31 in proliferation and neoplasia. PMID- 2597681 TI - Molecular cloning, coding nucleotides and the deduced amino acid sequence of P 450BM-1 from Bacillus megaterium. AB - The gene encoding barbiturate-inducible cytochrome P-450BM-1 from Bacillus megaterium ATCC 14581 has been cloned and sequenced. An open reading frame in the 1.9 kb of cloned DNA correctly predicted the NH2-terminal sequence of P-450BM-1 previously determined by protein sequencing, and, in toto, predicted a polypeptide of 410 amino acid residues with an Mr of 47,439. The sequence is most, but less than 27%, similar to that of P-450CAM from Pseudomonas putida, so that P-450BM-1 clearly belongs to a new P-450-gene family, distinct especially from that of the P-450 domain of P-450BM-3, a barbiturate-inducible single polypeptide cytochrome P-450:NADPH-P-450 reductase from the same strain of B. megaterium (Ruettinger, R.T., Wen, L.-P. and Fulco, A.J. (1989) J. Biol. Chem. 264, 10987-10995). PMID- 2597682 TI - Rotational dynamics of erythrocyte spectrin. AB - The rotational diffusion of erythrocyte spectrin has been measured using time resolved phosphorescence anisotropy. The anisotropy of the spectrin dimer decays to zero with a time constant of 3 microseconds at 21 degrees C. The results are compared with the correlation times predicted for the anisotropy decay of an equivalent sphere and rigid rod. The data indicate that the ribbon-like spectrin molecule possesses considerable torsional and segmental flexibility. These motions are restricted, but not abolished, when spectrin is reconstituted into cross-linked cytoskeletal protein networks, or bound to spectrin-actin depleted erythrocyte membrane vesicles. PMID- 2597683 TI - Solubilization of nuclear steroid 5 alpha-reductase from rat ventral prostate. AB - delta 4-Steroid-5 alpha-reductase (3-oxo-5 alpha-steroid:NADP+ delta 4 oxidoreductase, EC 1.3.1.22), is a membrane-bound enzyme. In the ventral prostate of the rat, its activity is found within the nuclear envelope. Solubilization of this enzyme can only be achieved in the presence of detergents. We studied the inhibitory effect of various detergents on 5 alpha-reductase activity as a function of detergent concentration, of pH, of incubation time, of salt concentration and of additives to the buffer system. Four detergents (Lubrol WX, CHAPS, L-alpha-lysophosphatidylcholine and octyl D-glucopyranoside) were selected for subsequent solubilization studies. The overall recovery of solubilized enzyme activity was about 30% when compared to 100% of 5 alpha-reductase activity found in freshly prepared nuclei. Up to 20-30% of the nuclear proteins were extracted during the solubilization procedure. Among the various treatments tested, a concentration of 3 mg/ml L-alpha-lysophosphatidylcholine per 10 mg/ml of nuclear protein in the presence of 5 mM MgCl2, 0.1 M KCl, 0.1 M sodium citrate and 5 mM NADPH yielded the maximal enzymic activity of 56%, 15% of the nuclear proteins being solubilized in an active and stable form. The activity in these extracts could be kept stable for 2 days at 4 degrees C with a recovery of 75% of enzymic activity. A 3-fold increase of specific 5 alpha-reductase activity was obtained during solubilization under optimal conditions. PMID- 2597684 TI - Glutathione transport across intestinal brush-border membranes: effects of ions, pH, delta psi, and inhibitors. AB - We characterized glutathione transport in brush-border membrane vesicles (BBMV) that were prepared from rabbit small intestine in which gamma-glutamyl transpeptidases (gamma-glutamyltransferases, EC 2.3.2.2) had been inactivated by a specific affinity-labeling reagent (AT125). Intact GSH transport was strongly increased by the presence of Na+, K+, LI+, Ca2+ and Mn2+ and, of all these, the Ca2+ activation effect was prevalent. This cation effect was selective and catalytic but not energetic; Vmax obtained in the presence of both Na+ and Ca2+ was about 6-times higher than it was in their absence, while Km did not change. Moreover, these cations almost completely eliminated GSH binding on the membrane surface. Na+ activation cannot be explained as a stimulation effect on the Na+-H+ antiport system, since a GSH proton-driven transport was excluded. We determined a pH optimum (7.5), while low or high extravesicular pH values diminished the GSH uptake rate. The Ca2+ effect on GSH transport, when an electrical potential difference was imposed across BBMV, was different from that of monovalent cations. Indeed, experiments performed by valinomycin-induced K+ diffusion potential or by anion substitution showed that the GSH transport system was an electroneutral process in the presence of Na+ or K+, but that it was electrogenic in the presence of Ca2+ or in the absence of extravesicular cations. These results suggest that GSH is also cotransported with these cations, without its accumulation inside vesicles. Moreover, since GSH is negatively charged, the effect of pH changes and of cation activation on GSH transport is arguably mediated by changes in the ionization state of certain groups as the carrier site and of GSH itself, indicating the electrostatic nature of GSH binding sites on the transporter. The high Ca2+ activation effect is perhaps also partly due to fluidity changes in the lipoproteic microenvironment of the GSH transporter. Moreover, this transport system has high affinity with GSH, given the low Km value (17 microM) and the fact that it was only inhibited by GSH S-derivatives and by GSH monoethyl ester, which probably share the same transport system. PMID- 2597685 TI - Renal Fanconi syndrome: developmental basis for a new animal model with relevance to human disease. AB - Using succinylacetone (SA), a metabolite of tyrosine excreted in excess by infants and children with hereditary tyrosinemia and the renal Fanconi syndrome (FS), we have investigated developmentally-related membrane transport events leading to emergence of the generalized renal tubular dysfunction seen in human FS. SA was found to impair sugar and amino acid uptake by both newborn renal tubules and 7-day renal brush-border membrane vesicles (BBMV). This impairment by SA was due in part to a slowing of substrate cotransport rate of 22Na+-entry into BBMV. Concentration-dependent uptake studies indicated SA inhibited the newborn high-affinity transport systems for sugars and amino acids. SA also caused an increase in membrane fluidity and a shift in the thermotropic transition temperature. The demonstrated dual nature of SA's effect on membrane fluidity and O2 consumption, together with the relative contribution of each component to SA induced transport impairment helps to provide a basis for an understanding of the age-related increases in glucosuria, aminoaciduria and natriuria seen in infants with FS. PMID- 2597686 TI - Immunoliposomes with different acid sensitivities as probes for the cellular endocytic pathway. AB - By combining dioleoylphosphatidylethanolamine (DOPE) with oleic acid (OA), palmitoylhomocysteine (PHC) or dipalmitoylsuccinylglycerol (DPSG) we have prepared pH-sensitive liposomes with different acid sensitivities. DOPE/OA liposomes are the most acid sensitive, while DOPE/DPSG liposomes are the least acid sensitive. Incubation of DOPE/OA liposomes with mouse L929 cells reduces the pH-sensitivity of these liposomes by altering the lipid composition. Using diphtheria toxin fragment A as a marker for cytoplasmic delivery, we find that the delivery kinetics of pH-sensitive immunoliposomes closely correlates with the modified acid sensitivities of the liposomes. Immunoliposomes encounter pH 6-6.2 with a t1/2 of 5-15 min after internalization. By contrast, acidification of the endosomes to pH 5.0 takes longer (t1/2 approximately 25 min). We also used a whole cell null point technique (Yamishiro and Maxfield (1987) J. Cell Biol. 105, 2713-2721) to directly determine the average pH encountered by the endocytosed immunoliposomes. We find that acidification determined by the null point method proceeds less rapidly than that estimated from DTA delivery data. This is likely due to the fact that the measured DTA delivery is done by those liposomes which first arrive at the endosomes with sufficient acidity. Our data suggests that DOPE/PHC immunoliposomes deliver at the early endosome while DOPE/DPSG immunoliposomes deliver at the late endosomes. The DOPE/OA immunoliposomes, with the altered composition and acid sensitivity, deliver with a kinetics intermediate between the other two immunoliposomes. Thus, pH-sensitive liposomes represent useful probes for studying the kinetics of endosome acidification. PMID- 2597687 TI - Differential affinity of charged local anesthetics to solid-gel and liquid crystalline states of dimyristoylphosphatidic acid vesicle membranes. AB - Cationic local anesthetics decreased the transition temperature of the anionic phospholipid (dimyristoylphosphatidic acid, DMPA) vesicles. The counterion concentration changes the electrical double layer effect, and affects the magnitude of temperature depression caused by anesthetics. From the counterion effect on the transition-temperature depression, the partition coefficients of cationic local anesthetics to liquid-crystalline and solid-gel DMPA membranes were separately estimated. The differences in the partition coefficients between solid-gel and liquid-crystalline membranes correlated to the nerve blocking potencies. There are at least two states in the nerve membranes: resting state at higher temperature and excited state at lower temperature. We speculate that the resting state corresponds to the liquid-crystalline state, and the excited state to the solid-gel state. The difference in the partition coefficients to the resting and excited states is the cause of local anesthesia. PMID- 2597688 TI - Ethanol increases agonist affinity for nicotinic receptors from Torpedo. AB - The presence of ethanol increases the apparent affinity with which acetylcholine and carbamylcholine elicit 86Rb+ flux from Torpedo nicotinic acetylcholine receptor-rich vesicles at 4 degrees C. Affinity increased exponentially with ethanol concentration, reaching nearly 200-fold by 3.0 M ethanol without sign of saturation. At submaximal agonist concentrations 50-100 mM ethanol enhanced flux by 15-35%, but the maximum agonist-induced flux was unaffected in quenched-flow assays. The effect was independent of the agonist and of the time over which flux was measured (5 ms to 10 s), indicating that ethanol acts before agonist-induced desensitization occurs. Ethanol also caused an increase in the apparent affinity with which acetylcholine caused fast desensitization. This affinity increase was equal to that for flux-response curves, but the maximum fast desensitization rate was increased 50% at 0.5 M ethanol. This was the most pronounced of ethanol's actions and has not been reported before. Prolonged preincubation with 1.0 M ethanol alone reduced agonist-induced flux activity by only 25%. The rate of agonist-induced slow desensitization was also increased, but neither of these effects was as marked as those on fast desensitization and cation flux. PMID- 2597689 TI - Psoralens sensitize glutathione photooxidation in vitro. AB - In vitro experiments are reported showing that psoralens and other furocoumarins of current pharmacological interest, e.g., angelicin and 4,6,4' trimethylangelicin, all have, to a variable extent, the ability to sensitize the photooxidation of glutathione in ethanol/phosphate buffer with pyrex-filtered ultraviolet light. Besides substrate concentration and the nature of the furocoumarin used, the rate of the sensitized reaction is markedly dependent on the partial pressure of oxygen and the pH of the medium, being progressively faster on passing from pH 5 to pH 8.5. Scavengers of superoxide ions (superoxide dismutase), hydrogen peroxide (catalase) and singlet oxygen (sodium azide, diazabicyclooctane, sorbic acid) have little or no inhibitory effect on the reaction rate. These and other data suggest that furocoumarins can directly sensitize glutathione photooxidation by forming a charge transfer complex which is driven to the oxidized products in the presence of oxygen. The possible relevance of these results to the mechanisms of skin melanin hyperpigmentation induced by furocoumarins and ultraviolet light is discussed. PMID- 2597690 TI - Fluorescence lifetime distributions of DNA-4',6-diamidino-2-phenylindole complex. AB - Time-resolved fluorescence of 4',6-diamidino-2-phenylindole (DAPI) complexes show that for a homogeneous polymer (polyd(AT) or polyd(A).polyd(T)) at high P/D (phosphate/dye) ratio, a single exponential component adequately describes the fluorescence decay. For the AT polymers at low P/D ratio or for native DNA, the decay cannot be described by a single-exponential term. A continuous distribution of lifetime values of Gaussian shape gives a good fit to the decay data. We propose that the lifetime distribution method for the analysis of the fluorescence decay of DNA-DAPI complexes provides a useful method of characterizing the microheterogeneity of site binding. PMID- 2597691 TI - The development expression of alpha-, mu- and pi-class glutathione S-transferases in human liver. AB - The developmental expression of the alpha, mu and pi class glutathione S transferases has been defined in human liver using radioimmunoassay and immunohistochemistry. Expression of alpha and mu class isoenzymes increased significantly at birth, while that of the pi isoenzyme declined during the first trimester. Mu-class isoenzymes (GST1 1, GST1 2, GST1 2-1) were expressed in hepatocytes but not in other liver cell types. PMID- 2597692 TI - Active transport and metabolic characteristics of polyamines in the rat lens. AB - Putrescine, spermidine and spermine were transported into the rat lens against a concentration gradient. This process appeared to be energy-dependent and involved a carrier system different from those for amino acids. Competition experiments suggested that the three polyamines were transported by the same system or very similar systems. Incorporated spermine was converted to spermidine and putrescine, and spermidine was converted to putrescine. In contrast, the conversion of putrescine to spermidine and spermine, or the conversion of spermidine to spermine was not observed. Furthermore, ornithine was not utilized for the synthesis of putrescine. These metabolic characteristics of the polyamines in the rat lens were correlated with the extremely low activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase. Other enzymes of polyamine metabolisms, however, were relatively active. In conclusion, the lens has a very low ability for the de novo synthesis of polyamines. The polyamines in the lens are considered to be supplied form the surrounding intraocular fluid by an active transport system specific for polyamines. PMID- 2597693 TI - Polyamine levels in red blood cells from patient groups of different sex and age. AB - Interpretation of polyamine levels found in the tissues and red blood cells of tumour patients has been plagued by the wide variations seen in the concentrations when estimated in groups of either tumour or control patients. To ascertain whether the patient's age or sex were contributing factors, red blood cell polyamine concentrations of 117 control patients were examined by high performance liquid chromatography. Concentrations of spermidine were consistently higher than those of spermine. Also, regression analysis showed that spermidine and spermine levels tended to change with age and sex, though these trends were statistically non-significant. PMID- 2597694 TI - Phosphate promotes glycation of antithrombin III which interferes with heparin binding. AB - Nonenzymatic glycation of antithrombin III has been reported to cause the reduction of heparin-catalyzed thrombin-inhibiting activity in diabetes. The effect of in vitro nonenzymatic glycation of pure antithrombin III on heparin binding and heparin-potentiated activity under a variety of buffers and pH values was studied to further clarify the physiological significance of this reaction. The extent of glycation, measured by the fructosamine assay and [14C]glucose binding, was enhanced by the presence of phosphate ion (pH 7.45, 8.5 and 9.5) and increased linearly with increasing phosphate ion concentration from 0.01 to 0.2 M phosphate. Conversely, the heparin-catalyzed antithrombin activity decreased from 93.1% of controls for 0.01 M phosphate to 73.5% for 0.2 M phosphate as the extent of glycation increased. The increase in intrinsic fluorescence induced by binding of heparin to antithrombin III was also moderated by glycation of antithrombin III in a dose-dependent manner with a negative correlation coefficient of -0.94. Direct measurement of the heparin binding by affinity chromatography showed a decrease in the heparin-binding fraction which correlated with the degree of glycation and the decrease in heparin-catalyzed activity. These studies suggest that nonenzymatic glycation may be responsible for the reduction in antithrombin III activity observed in some diabetics. PMID- 2597695 TI - Colchicine binding in the free-living nematode Caenorhabditis elegans. AB - The [3H]colchicine-binding activity of a crude supernatant of the free-living nematode Caenorhabditis elegans was resolved into a non-saturable component and a tubulin-specific component after partial purification of tubulin by polylysine affinity chromatography. The two fractions displayed opposing thermal dependencies of [3H]colchicine binding, with non-saturable binding increasing, and tubulin binding decreasing, at 4 degrees C. Binding of [3H]colchicine to C.elegans tubulin at 37 degrees C is a pseudo-first-order rate process with a long equilibration time. The affinity of C. elegans tubulin for [3H]colchicine is relatively low (Ka = 1.7 x 10(5) M(-1)) and is characteristic of the colchicine binding affinities observed for tubulins derived from parasitic nematodes. [3H]Colchicine binding to C. elegans tubulin was inhibited by unlabelled colchicine, podophyllotoxin and mebendazole, and was enhanced by vinblastine. The inhibition of [3H]colchicine binding by mebendazole was 10-fold greater for C. elegans tubulin than for ovine brain tubulin. The inhibition of [3H]colchicine binding to C. elegans tubulin by mebendazole is consistent with the recognised anthelmintic action of the benzimidazole carbamates. These data indicate that C. elegans is a useful model for examining the interactions between microtubule inhibitors and the colchicine binding site of nematode tubulin. PMID- 2597696 TI - Analysis of dolichyl pyrophosphoryl oligosaccharides in purified storage cytosomes from ovine ceroid-lipofuscinosis. AB - Ovine ceroid-lipofuscinosis is an inherited neurodegenerative disorder characterised by the accumulation of storage cytosomes in brain and visceral organs. Phosphorylated dolichol-containing compounds, largely in the form of dolichyl pyrophosphoryl oligosaccharides, have been shown to constitute 1-2% of the dry weight of storage cytosomes isolated from brain and pancreas, and 0.5 and 0.1% respectively of storage cytosomes isolated from liver and kidney. The carbohydrate portion of these glyconjugates in storage cytosomes isolated from brain, pancreas and liver consisted of a series of oligosaccharides of composition Man2-9GlcNAc2, with Man5-8GlcNAc2 predominating. The concentrations of dolichyl pyrophosphoryl oligosaccharides in storage cytosomes from ovine ceroid-lipofuscinosis are much higher than has been reported for endoplasmic reticulum, their normal functional location. PMID- 2597697 TI - A critical evaluation of urinary immunoreactive thromboxane: feasibility of its determination as a potential vascular risk indicator. AB - Urinary immunoreactive thromboxane (irTXB2) has been found helpful in acute settings with altered renal, but also extrarenal thromboxane formation. As only trace amounts of systemically formed thromboxane are excreted unmetabolized, the nature of urinary irTXB2 was explored. The two most abundant metabolites of systemic thromboxane, 2,3-dinor-TXB2 and 11-dehydro-TXB2, crossreacted about 70% and less than 1%, respectively, with a widely used thromboxane antiserum. After solid-phase extraction of urine samples and separation on reversed-phase HPLC, the bulk of immunoreactivity always eluted as one peak shown to correspond to 2,3 dinor-TXB2. Much less was found in fractions where TXB2 eluted. Therefore, urines were read against calibration curves constructed with 2,3-dinor-TXB2. This direct estimation gave good recoveries for standard 2,3-dinor-TXB2 and correlated well, both in healthy controls and in patients at increased risk or with overt vascular disease, to values obtained after solid phase extraction, purification on reversed-phase HPLC and quantitation by either gas-chromatography mass spectrometry or radioimmunoassay. Patients with multiple cardiovascular risk factors but free from detectable vascular disease excreted significantly more irTXB2 than age-matched controls with non-vascular conditions or normals. Therefore, urinary irTXB2 measured with this antiserum represents 2,3-dinor-TXB2, reflecting the systemic formation of TXB2. This simple approach is feasible for screening thromboxane formation in large series of patients. Its acumen in detecting the early development of vascular disease and its relation to established risk factors deserves large-scale prospective testing. PMID- 2597698 TI - Purification and characterization of two cellobiohydrolases from Chaetomium thermophile var. coprophile. AB - Cellobiohydrolases I and II were purified to homogeneity from culture filtrates of a thermophilic fungus, Chaetomium thermophile var. coprophile, by using a combination of ion-exchange and gel filtration chromatographic procedures. The molecular weights of cellobiohydrolase I and II were estimated to be 60,000 and 40,000 and the enzymes were found to be glycoproteins containing 17 and 22.8% carbohydrate, respectively. The two forms differed in their amino-acid composition mainly with respect to threonine, alanine, methionine and arginine. Antibodies produced against either form of cellobiohydrolases failed to cross react with the other. The tryptic maps of the two enzymes were found to be different. The temperature optima for cellobiohydrolase I and II were 75 and 70 degrees C, and they were optimally active at pH 5.8 and 6.4, respectively. Both enzymes were stable at higher temperatures and were able to degrade crystalline cellulosic materials. PMID- 2597700 TI - Interaction of Campylobacter jejuni with extracellular matrix components. AB - The adhesion of three strains of Campylobacter jejuni to coverslips and microwells coated with isolated extracellular matrix components, fibronectin, laminin and types I, III, IV and V collagens was studied. Fibronectin mediated the adherence of C. jejuni, but there were differences in the binding capacities of the strains. Type I, III and V collagens mediated very strongly the attachment of two strains of C. jejuni. All three strains attached weakly to basement membrane-specific type IV collagen. Laminin was capable of mediating the adhesion only when present at a higher concentration. The observations indicate that extracellular matrix components may serve as anchor molecules for C. jejuni adhesion and that several attachment mechanisms occur simultaneously. PMID- 2597699 TI - Purification and properties of a new ribosome-inactivating protein with RNA N glycosidase activity suitable for immunotoxin preparation from the seeds of Momordica cochinchinensis. AB - A ribosome-inactivating protein similar to those already known (Stirpe and Barbieri (1986) FEBS Lett. 195, 1-8) was purified from the seeds of Momordica cochinchinensis. This protein, for which the name of momorcochin-S is proposed, is a glycoprotein, has an Mr of approx. 30,000, and an alkaline isoelectric point and can be considered as an iso-form of the previously purified momorcochin from the roots of M. cochinchinensis. Momorcochin-S inhibits protein synthesis by a rabbit-reticulocyte lysate and phenylalanine polymerization by isolated ribosomes, and alters rRNA in a similar manner as the A-chain of ricin and related toxins (Endo et al. (1987) J. Biol. Chem. 262, 5908-5912). Momorcochin-S was linked to a monoclonal antibody (8A) against human plasma cells, and the resulting immunotoxin was selectively toxic to target cells. PMID- 2597701 TI - Rat plasma kallikrein: purification, NH2-terminal sequencing and development of a specific radioimmunoassay. AB - Rat plasma kallikrein (rPK) was purified to homogeneity form plasma using affinity and high-performance liquid chromatography techniques, and subjected to NH2-terminal sequencing. The data showed that the sequenced segments of the regulatory (heavy) and catalytic (light) chains of the proteinase, respectively, display 73 and 91% sequence similarity with their counterpart in human plasma kallikrein. This sequence homology in conjunction with the determined molecular structure and inhibitor sensitivity support the identity of the isolated enzyme as plasma kallikrein. A polyclonal antiserum against rPK was obtained after immunization of rabbits with the purified enzyme, and a specific radioimmunoassay was developed. Since Tyr-iodinated rPK was not recognized by the antiserum, two alternative approaches were found to be successful. These included the use of a tracer consisting of rPK modified with either the affinity reagent 125I-labeled DTyr-Glu-Phe-Lys-Arg chloromethyl ketone or with the Bolton Hunter reagent. The usable range of the assay is between 15-150 fmol per tube. The antibody was shown to bind both monomeric and dimeric forms of rPK. Denaturation of the enzyme in sodium dodecyl sulfate does not abolish immune recognition only as long as the regulatory subunit is attached to the catalytic chain. Oxidation or reduction of rPK results in complete loss of immunoreactivity. This observation suggests that perhaps the disulfide linkage of the catalytic and regulatory polypeptides somehow helps to protect the antigenic epitope from denaturation. Alternatively, the epitope(s) recognized by the antibody spans a domain which includes both Tyr and Cys residues necessary for immune recognition. PMID- 2597702 TI - Bile salts-bovine serum albumin binding: spectroscopic and thermodynamic studies. AB - The binding of hydroxyl and keto bile salts to bovine serum albumin was studied by fluorescence and circular dichroism spectroscopies. It was found that the hydroxyl and keto bile salts produced a quenching of the native fluorescence emission of the protein at 350 nm. In the ligand-protein saturation conditions, cholanate-3-one, cholanate-3,6-dione and beta 5-cholanate produced a 100% fluorescence quenching, while hydroxy bile salts produced only a 50% quenching. This demonstrates that the two tryptophan residues of the protein are accessible to the keto bile salts, while only one tryptophan residue is accessible to the hydroxy parent compounds. Keto bile salts produced a change in the circular is related to a microrearrangement of the environment at the albumin-binding sites. All the tested bile salts produced quenching of the fluorescence probe, 1-aniline 8-naphthalene sulfonate, which is not covalently bound to the protein. This effect is due to an energy transfer between the tryptophan residues and the acceptor fluorescence probe. The binding of hydroxyl bile salts was associated with an endothermic process, while keto bile salts-albumin interaction was associated with a negative enthalpic change. PMID- 2597703 TI - Purification and properties of a membrane-bound NADH-cytochrome-b5 reductase from erythrocytes of the sipunculid worm, Phascolopsis gouldii. AB - The purification to homogeneity of the membrane-bound NADH-cytochrome-b5 reductase from erythrocytes of the sipunculid, Phascolopsis gouldii is reported. This highly purified reductase has allowed more detailed characterizations of its molecular and kinetic properties than was possible in a previous study (Utecht, R.E. and Kurtz, D.M., Jr. (1988) Biochim. Biophys. Acta 953, 164-178). The reductase has a molecular weight of 34,000 and contains FAD as the prosthetic group. In aqueous solution containing 0.5 vol% Triton X-100, the reductase forms an aggregate of Mr approximately 220,000. A higher purity preparation of P. gouldii erythrocyte b5 was also obtained. The combination of purified, solubilized reductase and cytochrome b5 was shown to catalyze the quantitative two-electron reduction of [Fe(III),Fe(III)]methemerythrin to [Fe(II),Fe(II)]deoxyhemerythrin by NADH. The P. gouldii NADH-cytochrome b5 reductase is the first from hemerythrin-containing erythrocytes to be purified and characterized. This methemerythrin reduction system appears to be analogous to methemoglobin reductases from vertebrate erythrocytes. PMID- 2597704 TI - Further purification and characterization of the succinyl-CoA:3-hydroxy-3 methylglutarate coenzyme A transferase from rat-liver mitochondria. AB - Succinyl-CoA:3-hydroxy-3-methylglutarate coenzyme A transferase, previously identified in rat-liver mitochondria (Deana et al. (1981), Biochim. Biophys. Acta 662, 119-124), was purified to near homogeneity and further characterized. After the last purification steps consisting of Ultrogel AcA-44 filtration and agarose hexane-coenzyme A chromatography, the enzyme was apparently tetrameric with a mass of 48-52 kDa determined by gel filtration on Sephadex G-75, ultracentrifugation through a sucrose gradient and SDS-gel electrophoresis. By means of a HPLC technique developed for measuring the CoA esters we could determine the enzyme activity in both forward and reverse directions and show that the kinetic constants, i.e., Km of reactants and Vmax, are not too different for the two reactions. Double-reciprocal plots of the enzyme velocities versus the concentration of one substrate at different fixed concentrations of the other substrate gave families of straight lines converging below the substrate-abscissa for both forward and backward reactions, indicating a kinetic mechanism of rapid equilibrium random Bi-Bi type. The competitive inhibition of the product succinate with respect to both reactants, 3-hydroxy-3-methylglutarate and succinyl-CoA, as well as the Haldane relationships are consistent with this conclusion. An inhibitory effect on CoA transferase activity by acetate, acetoacetate, acetyl-CoA, acetoacetyl-CoA, coenzyme A, carnitine, ZnCl2 and high concentrations of the monovalent anions ClO4-, F-, I- and Cl- was also found. PMID- 2597705 TI - Proteins of Newcastle disease virus envelope: interaction between the outer hemagglutinin-neuraminidase glycoprotein and the inner non-glycosylated matrix protein. AB - Using linear sucrose-density ultracentrifugation analysis of Triton-solubilized Newcastle Disease Virus envelopes, we have evidenced, for the first time, the existence of interactions between the outer hemagglutinin-neuraminidase transmembrane glycoprotein and the inner non-glycosylated peripheral matrix protein. Such interactions seem to be electrostatic. These conclusions are based on the behavior of both proteins at different ionic strengths. When in low ionic strength buffer, hemagglutinin-neuraminidase and matrix proteins band together in the sucrose gradient, whereas at high ionic strength both proteins band at different rates in the gradient. The behavior of the inner matrix protein in our conditions was the expected one for a peripheral protein. The results of these 'in vitro' studies are also discussed in terms of the possible 'in vivo' role of such interactions. PMID- 2597706 TI - Purification and partial characterization of platelet-derived adherence inhibiting factor in guinea pig. AB - Purification and partial characterization of adherence-inhibiting factor (AIF) of platelet-granule fraction in guinea pig were studied. When freshly prepared platelet-granule fraction was subjected to a gel filtration, two neutrophil adherence-inhibiting peaks, designated AIF-I (2,800 kDa) and AIF-II (12 kDa), appeared. AIF-I was sensitive to diisopropylfluorophosphate (DFP) and originated from lysosomes, whereas AIF-II was insensitive to DEP and localized in alpha granules. Both AIFs were released from platelets by a thrombin stimulation. As the total activity of AIF-I was about 5-fold higher than that of AIF-II, AIF-I was purified and characterized. When purified AIF-I was analyzed on SDS polyacrylamide gel electrophoresis, the 340 kDa protein band and the other large protein band were observed. Under reducing condition, AIF-I was separated into three components (340, 190 and 165 kDa). AIF-I significantly inhibited neutrophil adherence to artificial substrata and to type IV collagen-coated plastic surface, but not to fibronectin- or plasma-coated plastic surfaces, suggesting that AIF-I inhibits neutrophil adherence not only via nonspecific adsorption sites but also via type IV collagen receptors. PMID- 2597707 TI - Raman spectroscopic study of the changes in secondary structure of chymotrypsin: effect of pH and pressure on the salt bridge. AB - Conformational changes of alpha-chymotrypsin, induced by pH and pressure, have been studied with Raman spectroscopy. The secondary structure of alpha chymotrypsin, chymotrypsinogen and DFP-chymotrypsin has been calculated by a singular value analysis of the Raman amide-I band. The changes in secondary structure, with pH and pressure titration of alpha-chymotrypsin, indicate a conformational transition. The salt bridge between Asp-194 and Ile-16 is disrupted, and the enzyme becomes inactive. No changes are observed for chymotrypsinogen. It is concluded that the proenzyme exhibits the same conformation at different pH values as alpha-chymotrypsin at alkaline pH. The results for DFP-chymotrypsin indicate that the active conformation is stabilized by the presence of the DFP inhibitor in the binding site. PMID- 2597708 TI - Primary structure of ammodytoxin C further reveals the toxic site of ammodytoxin. AB - The sequence of ammodytoxin C, a presynaptically toxic, basic phospholipase A2 of Vipera ammodytes ammodytes venom was determined. The toxin differs only in two amino acid residues from the most toxic isotoxin ammodytoxin A and is 18-times less lethal. Ammodytoxin B which is 30-times less lethal than ammodytoxin A differs from it only in three amino acid residues. From the three-dimensional model of ammodytoxin A, it can be seen that mutated regions of ammodytoxin B and ammodytoxin C are on the surface, and relatively distant from each other. The observed decrease in toxicity of ammodytoxin C could be a consequence of changed charge in position 128 where a Lys is exchanged for Glu. The resulting change in electrostatic properties of the molecule which influences the orientation of the molecule during the approach to the charged nerve-terminal membrane might be responsible for the observed decrease in toxicity. PMID- 2597710 TI - Neither a mentalist nor a reductionist be! AB - There is basis for concern that applied psychophysiology, if not the field of biofeedback, is being coopted by, and merged into, a reborn "inner" model, with the return of "cognition" to preeminence in the "psych" and "neuro" disciplines. Despite currently fashionable views that such mentalistic inventions and neuro/psychological developments somehow illuminate behavior or offer simpler accounts of behavioral facts, there is little or no evidence that any such construction has ever told us anything new about behavior. PMID- 2597709 TI - Tryptophan environments in glutathione transferase of human placenta from temperature-dependent phosphorescence studies. AB - An investigation of the tryptophan emission properties of glutathione transferase from human placenta was conducted in order to characterize the environments of the two aromatic residues. The low-temperature phosphorescence spectra and temperature dependence of the phosphorescence quantum yield of the tryptophan residues revealed a difference in the chemical nature and dynamical structure of the surrounding protein matrix. Thus, one tryptophan residue seems to be deeply embedded within the polypeptide in a rigid weakly polar environment, characteristic of a beta-type secondary structure. The other is located in a more polar site, probably near the surface, in a rather flexible region of the macromolecule. At high temperature, the heterogeneity in the triplet lifetime of the internal residue attests to the presence of multiple conformers which are not in rapid equilibrium in the phosphorescence time scale. The anisotropy of the phosphorescence emission of glutathione transferase indicates that no energy transfer occurs between the two residues, and measurement of the rotational correlation time yields an hydrodynamic volume which is in good agreement with the molecular weight reported in the literature for the dimer. PMID- 2597711 TI - Blood glucose discrimination training in patients with type II diabetes. AB - This study was designed to determine whether patients with Type II diabetes could be taught to discriminate blood glucose after experiencing a variety of blood glucose levels and receiving feedback on the accuracy of their estimates. Thirty six subjects (18 on oral agents and 18 on insulin) were randomly assigned to one of two feedback conditions: (1) current feedback, which received accurate information regarding their blood glucose levels, (2) noncurrent feedback, which received blood glucose levels from the preceding session. Subjects were exposed to a wide range of blood glucose values in six training sessions by ingesting drinks with three different caloric loads. In pre/post comparisons using several indices of accuracy, both groups showed significant improvement in estimating blood glucose levels. However, feedback on current blood glucose levels did not produce greater improvement than noncurrent. Accuracy was unrelated to the degree to which subjects reported associating internal sensations to their estimates. Failure to find differences between the two feedback conditions may have been due to the noncurrent feedback group's receiving fairly accurate information, to the difficulty of the discrimination task, and to the limited number of training trials. PMID- 2597713 TI - The use and utility of EMG biofeedback with chronic schizophrenic patients. AB - This study examined the efficacy of muscle relaxation training via electromyographic (EMG) biofeedback from the frontalis and forearm extensor muscles of schizophrenic inpatients. Thirty chronically hospitalized patients were randomly assigned to one of three conditions: EMG biofeedback from the forearm extensor and frontalis muscles, progressive relaxation, and a control group. Treatment consisted of one session of orientation and baseline, and six sessions of training. The results indicated that the schizophrenic patients receiving EMG training had significantly lower EMG recordings than the progressive relaxation group, which, in turn, was significantly lower than the control group. Analyses of covariance on the Tension-Anxiety scale from the Profile of Mood States revealed no significant effects, while finger-tapping rates were significantly improved only for the arm receiving feedback training in the EMG group. On the Nurses Observation Scale for Inpatient Evaluation the biofeedback group significantly improved on the Social Competence and Social Interest factors. PMID- 2597712 TI - Behavioral treatment of isolated systolic hypertension in the elderly. AB - Fifteen hypertensive patients were recruited from a geriatric medicine clinic for a "research project designed to evaluate a Behavioral Stepped-Care treatment program of high blood pressure (HBP)." All patients met the selection criteria of the Isolated Systolic Hypertension (ISH) in the Elderly (SHEP) clinical trial. During baseline, subjects recorded BP at home 9 times/day (3 times each, shortly after awakening, during the middle of the day, and within an hour of retiring) for 1 month and mailed that data to us daily. In addition, they came to the clinic weekly and had their BP recorded by a nurse. During treatment 1, systolic (SBP) feedback, they were trained to lower SBP at home using their sphygmomanometers. They also continued to monitor BP and to obtain weekly professional BP readings. During treatment 2 (relaxation), they were trained to relax; they followed the self-administration and data-collection protocol as in treatment 1. Each treatment phase lasted 3 months. Average monthly self determined BP fell significantly from 166.4/85.8 (SBP/DBP) mm Hg during baseline to 153.3/81.2 by the end of the relaxation phase; average monthly professionally measured BP fell significantly, from 164.7/87.1 to 156.9/81.5. These findings show that a nurse-supervised, patient-administered behavioral treatment program of ISH can yield sustained, significant falls in BP. PMID- 2597715 TI - The hyperventilation syndrome. PMID- 2597714 TI - Effect of music-assisted imagery on neutrophils and lymphocytes. AB - The purpose of this study was to determine the effects of cell-specific mental imagery on neutrophil and lymphocyte cell counts. Subjects (N = 30) were randomly assigned to one of two experimental groups that underwent a 6-week training program focusing on images of morphology, location, and movement of either neutrophils or lymphocytes. Music was used to enhance the imagery of the subjects. Peripheral white blood cell and differential counts were determined before and after the final 20-minute imagery session. Results indicated that neutrophils decreased significantly (p less than .04) in the neutrophil-change group while lymphocytes did not. The reverse occurred in the lymphocyte-change group, with only the lymphocytes decreasing significantly (p less than .03). The authors concluded that under the conditions of the present study, cell-specific imagery was associated with decreases in peripheral blood cell counts of lymphocytes and neutrophils. PMID- 2597716 TI - Structure-from-motion by tracking occlusion boundaries. AB - Active visual tracking of points on occlusion boundaries can simplify certain computations involved in determining scene structure and dynamics based on visual motion. Tracking is particularly effective at surface boundaries where large, discontinuous changes in depth are occurring. Two such techniques are described here. The first provides a measure of ordinal depth by distinguishing between occluding and occluded surfaces at a surface boundary. The second can be used to determine the direction of observer motion through a scene. PMID- 2597717 TI - Stereo and eye movement. AB - We describe a method to solve stereo correspondence using controlled eye (or camera) movements. Eye movements supply additional image frames and monocular depth estimate, which can be used to constrain stereo matching. Because the eye movements are small, traditional stereo techniques of stereo with multiple frame will not work. We develop an alternative approach using a systematic analysis to define a probability distribution for the errors. Our matching strategy then matches the most probable points first, thereby reducing the ambiguity for the remaining matches. We demonstrate this algorithms with several examples. PMID- 2597718 TI - Analysis of the Lynch-Granger model for olfactory cortex. AB - The behavior of the Lynch-Granger model for layer-II piriform cortex is reviewed, and a simple neural model with similar properties is introduced. This model allows us to understand the observed functionality of the Lynch-Granger model intuitively, and suggests which of the many biological facts introduced into the original model are relevant to this particular behavior. PMID- 2597719 TI - Looking into the water with a facet eye. AB - The apparent velocity and apparent size of objects approaching an animal strongly depend on their size, their position within the visual field and on the path along which they move. It also makes a considerable difference whether both the animal and the objects are in air, or whether the animal looks from one medium into the other, as is the case in animals that live at the water surface. To systematically investigate this situation we calculated apparent velocity and size in the midsagittal plane of approaching objects of flat horizontal, rodlike vertical and spherical shape. We confine our investigation to object movements along straight horizontal and vertical paths and consider the situation for eyes with and without acute zones. The apparent velocity of an approaching object is low in the far field and increases rapidly close to the eye in both air and water. Along horizontal paths and close to the animal it is higher in water than in air. Along vertical paths and close to the animal it is higher in air than in water. Both relationships are exaggerated when there is an acute zone for vertical resolution along the animal's horizon. Boundary curves are calculated along which an approaching object is seen by a linearly increasing number of receptors. The change of apparent size is characterized by the density of these lines. Below the water surface the change of apparent size is similar to that of the apparent velocity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2597720 TI - Saltatory transitions are a naturally occurring property of evolving systems. AB - On the basis of paleological evidence, it has been suggested that biological evolution need not necessarily be characterized by gradual change. Rather, evolutionary history may display saltatory periods of rapid speciation alternating with periods of relative quiescence, the whole dynamic being called punctuated equilibria. The empirical evidence that has been presented in support of this hypothesis has been the object of a vigorous dispute. Mathematical investigations of complex models of biological evolution that contain random elements have demonstrated that these systems can display saltatory behavior. In this paper we address a more abstract question: can saltations occur in the evolution of very simple, deterministic mathematical systems that function in a constant environment? The answer appears to be yes. Saltations appear as a natural dynamical behavior in the evolution of simplistic information processing networks. We stress that these networks do not constitute a model of biological evolution. However, the appearance of saltations in such simple systems suggests that their appearance in a process as complex as biological evolution is not surprising. PMID- 2597721 TI - On the existence of limit cycles in motion field. AB - In this paper we show the existence of limit cycles in the vector field generated by the perspective projection on the image plane of the velocity field of a moving surface. The existence of limit cycles is proved with the Poincare Bendixon theorem, in the case of a rotating smooth non-planar surface and illustrated with computer graphics. The structural stability of the limit cycles is also discussed. PMID- 2597722 TI - Protein complexation with DNA phosphates as a cause for DNA duplex destabilization: a thermodynamic model. AB - Complexation of positively charged sites in a protein with the negative DNA phosphate groups shields the phosphate charges. This diminishes interstrand electrostatic repulsions, which stabilizes the duplex. When phosphate shielding is present in one DNA strand only, the conformation of this strand changes due to a decrease of intrastrand phosphate-phosphate repulsions. This destabilizes the duplex since then the strands differ in conformation. A thermodynamic model is formulated to describe this stabilization/destabilization effect in terms of changed enthalpies and entropies of hybridization. It is found that protein complexation with one DNA strand can indeed lower the TM value of a duplex. The model is applied to the action of helicases (replication), RNA polymerases (transcription), and restriction endonucleases. Mechanisms with unilateral charge shielding are proposed for their duplex-destabilizing properties. PMID- 2597723 TI - Theory of cooperative transitions in protein molecules. I. Why denaturation of globular protein is a first-order phase transition. AB - A theory of equilibrium denaturation of proteins is suggested. According to this theory, a cornerstone of protein denaturation is disruption of tight packing of side chains in protein core. Investigation of this disruption is the object of this paper. It is shown that this disruption is an "all-or-none" transition (independent of how compact is the denatured state of a protein and independent of the protein-solvent interactions) because expansion of a globule must exceed some threshold to release rotational isomerization of side chains. Smaller expansion cannot produce entropy compensation of nonbonded energy loss; this is the origin of a free-energy barrier (transition state) between the native and denatured states. The density of the transition state is so high that the solvent cannot penetrate into protein in this state. The results obtained in this paper make it possible to present in the following paper a general phase diagram of protein molecule in solution. PMID- 2597724 TI - Theory of cooperative transitions in protein molecules. II. Phase diagram for a protein molecule in solution. AB - The thermodynamically stable states of denatured protein in solution are investigated. These states are distinguished from the native state by the absence of tight packing of side chains while the compactness of denatured protein may vary within a wide region. The following regimes are outlined: 1. the "wet" molten globule, i.e., the compact state with pores occupied by solvent; 2. the swollen globule ("wet," of course); and 3. the coil. The "dry" molten globule, when solvent does not penetrate inside the protein, is excluded for all experimental conditions. All the transitions within the denatured globule state are gradual while the denatured globule-coil phase transition is a second order one. The conditions of protein denaturation as well as conditions of transitions and crossovers within the denatured state are outlined. PMID- 2597725 TI - Effects of chloroquine on the torsional dynamics and rigidities of linear and supercoiled DNAs at low ionic strength. AB - The magnitude and uniformity of the torsion elastic constant (alpha) of linear and supercoiled pBR322 DNAs are measured in 3 mM Tris as a function of added chloroquine/basepair ratio (chl/bp) by studying the fluorescence polarization anisotropy of intercalated ethidium dye. The time-resolved FPA is measured using a picosecond dye-laser for excitation and time-correlated single-photon counting detection. For both linear and supercoiled DNAs, alpha remains uniform except at the very highest chl/bp ratio examined. For the linear DNA, alpha decreases from 5.0 x 10(-12) dyne-cm at chl/bp = 0 to about 3.5 x 10(-12) dyne-cm at chl/bp = 0.5, and remains at that value up to chl/bp = 5, whereupon it increases back up to its original value. For the supercoiled DNA, alpha remains constant at about 5.2 x 10(-12) dyne-cm from chl/bp = 0 up to chl/bp = 5, whereupon it increases in parallel with the linear DNA. The effect of chloroquine on the secondary structure, torsion constant, and torsional dynamics evidently differs substantially between linear and supercoiled DNAs, even under conditions where the supercoiled DNA is completely relaxed and both DNAs bind the same amount of dye. This strongly contradicts any notion that the local structures of linear and relaxed supercoiled DNA/dye complexes with the same binding ratio are identical. The increase in apparent alpha at chl/bp = 5 for both DNAs may be due to stacking of the chloroquine in the major groove and consequent stiffening of the filament. PMID- 2597726 TI - Allosteric formulation of thermal transitions in macromolecules, including effects of ligand binding and oligomerization. AB - We examine the effects of concentration (aggregation), buffers, and ligation, under conditions of either constant ligand activity or limited total amount of ligand, upon thermal denaturation of macromolecules as measured by scanning calorimetry. In doing so we utilize and extend an earlier generalized allosteric treatment [S. J. Gill, B. Richey, G. Bishop, and J. Wyman (1985) Biophys. Chem. 21, 1-14], applicable to ligand binding, enthalpy changes, and volume changes in a macromolecular system. The approach is contrasted with formulations based on the idea of structural domains. We show how information from the full scanning calorimetric curves can be utilized in arriving at and testing appropriate models for observed behavior in selected examples. PMID- 2597727 TI - Conformational transitions of leucine-containing isomeric sequential basic polytripeptides. AB - Conformational transitions of basic sequential polytripeptides (Lys-Ala-Leu)n, (Arg-Ala-Ala)n, (Arg-Leu-Ala)n, and (Arg-Ala-Leu)n, induced by elevated salt concentrations and/or temperatures in aqueous solutions, were investigated by CD, sedimentation equilibrium, and viscometry. The behavior of (Lys-Ala-Leu)n was compared with that of the sequential isomer (Lys-Leu-Ala)n, studied previously. It was found that both polypeptides are highly helical with a tendency to aggregate in high salt solutions. Although the hydrophobic interactions between Lys and Leu residues play an important role in both cases, the final effect on helix stabilization and aggregation is different. The Arg-containing polypeptides were found to assume the alpha-helical conformation. Compared to the Lys containing polypeptides (Lys-Ala-Leu)n and (Lys-Leu-Ala)n, a very low tendency to aggregate was observed. PMID- 2597728 TI - Inverted repeat sequences can influence the melting transitions of linear DNAs. AB - The influence of inverted repeat sequences on the melting transitions of linear DNAs has been examined. Derivative melting curves (DMC) of a 514 base pair (bp) DNA, seven subfragments of this DNA, and four other DNAs have been compared to predictions of DNA melting theory. The 514-bp DNA contains three inverted repeat sequences that can form cruciform structures in supercoiled DNA. We refer to these sequences as c-inverted repeats. Previous work showed that the DMC of this DNA, unlike a number of other DNAs, is not accurately predicted by DNA melting theory. Since the theoretical model does not include hairpin-like structures, it was suggested that hairpin or cruciform formation in these inverted repeats may be responsible for this discrepancy. Our results support this hypothesis. Predicted DMCs are in good agreement with DNAs with no inverted repeats, or inverted repeats not evident in supercoiled DNA. Differences between the theoretical and experimental Tm's are less than or equal to 0.3 degrees C. DNA molecules that contain one or more of the three c-inverted repeats are not as accurately predicted. Experimental Tm values are lower than predicted values by 0.7-3.8 degrees C. It is concluded that some inverted repeat sequences can form hairpin-like structures during the melting of linear DNAs. These structures appear to lower overall DNA stability. PMID- 2597729 TI - IR vibrational CD in alanyl tripeptide: indication of a stable solution conformer. AB - Infrared vibrational CD (VCD) of a small peptide, L-alanyl-L-alanyl-L-alanine (Ala3), and a peptide model, N-acetyl-L-alanine-N'-methyl-amide (AAMA), in the 1550-1750-cm-1 region has been observed. The "coupled oscillator" VCD feature observed for Ala3 in the amide I region is interpreted in terms of a solution structure stabilized by the electrostatic interaction of the zwitterionic groups. No such interactions are possible in basic aqueous solution of Ala3 nor in AAMA in neutral solution. Thus, the coupled oscillator features are lost in the latter two cases, indicating the absence of a simple stabilized conformation. PMID- 2597730 TI - Solution conformation of the actinomycin D related pentapeptide lactone using NMR and molecular modeling. AB - A detailed description of the two observed solution conformations of the pentapeptide lactone fragment of actinomycin D is presented using the distance constraints obtained from two-dimensional nuclear Overhauser enhancement spectra in combination with minimum energy calculations. Low energy conformational states that are compatible with the experimental distances are found for each of the two conformers. For one conformer, an all trans peptide bond conformer, is found with no intramolecular hydrogen bonds. For the other conformer, the D-Val-Pro and Pro Sar peptide bonds were cis; this solution conformation is the same as that found in both the crystal structure of the pentapeptide lactone as well as of the native actinomycin D itself. These results are discussed in terms of the combined influence of conformation and the effects of mutual intramolecular association of the pentapeptide lactone moieties in native actinomycin D on its cytotoxic activity. PMID- 2597731 TI - The biased reptation model of DNA gel electrophoresis: mobility vs molecular size and gel concentration. AB - The biased reptation model provides a good framework for interpreting the results of continuous field DNA electrophoresis experiments performed in agarose gels. Here we discuss the main features of the mobility-molecular size and mobility-gel concentration diagrams as obtained from new extensive computer simulations of the model. Our aim is to suggest a global and coherent picture of this widely used yet poorly understood experimental technique, and to point out the areas where a systematic experimental study is still needed. PMID- 2597732 TI - DNA gel electrophoresis: effect of field intensity and agarose concentration on band inversion. AB - We study the effect of electric field intensity and agarose gel concentration on the anomalous electrophoretic mobility recently predicted by the biased reptation model and experimentally observed for linear DNA fragments electrophoresed in continuous electric fields. We show that high fields and low agarose concentrations eliminate the physical mechanism responsible for anomalous DNA mobility and band inversion, in good agreement with theory, thus restoring the monotonic mobility-size relationship necessary for unambiguous interpretation of the results of DNA gel electrophoresis. PMID- 2597733 TI - The influence of the side-chain sequence on the structure-activity correlations of immunomodulatory branched polypeptides. Synthesis and conformational analysis of new model polypeptides. AB - New branched polypeptides were synthesized for a detailed study of the influence of the side-chain structure on the conformation and biological properties. The first subset of polypeptides were prepared by coupling of tetrapeptides to poly[L Lys]. These polymers contain either DL-Ala3-X [poly[Lys-(X-DL-Ala3)n]] or X-DL Ala3 [poly[Lys-(DL-Ala3-X)n] (n less than or equal to 1)] tetrapeptide side chains. Another group of branched polymers comprise a mixture of DL-Alam and of DL-Alam-X oligomeric branches in a random distribution [poly[Lys-(DL-Alam-Xi)] (i less than 1, m approximately 3)]. In each subset the X = Leu or Phe derivatives were prepared. The N-protected tetrapeptides were synthesized by conventional liquid phase methods and were coupled as active esters. The degree of racemization was found relatively high both for active esters and coupled derivatives, when optically active amino acids were in the C-terminal position of the tetrapeptides. In the case of the poly[Lys-(Leu-DL-Ala3)n] derivative, comparative experiments were carried out using various methodical alterations. The highest stereochemical homogeniety could be achieved when the tetrapeptide active ester was synthesized by the "backing off" method. CD spectra of poly[Lys (Xi-DL-Alam)] (i less than 1, m approximately 3) and of poly[Lys-(X-DL-Ala3)n] were analyzed and compared to those of poly[Lys-(DL-Alam-Xi)] and of poly[Lys-(DL Ala3-X)n]. All measurements were performed in water solutions of varying pH values and ionic strengths. The data obtained suggest that branched polypeptides containing a mixture of two different types of oligomeric side chains (DL-Alam and DL-Alam-Xi or Xi-DL-Alam) distributed randomly adopt an almost identical conformation to those that comprise only the respective tetrapeptide (DL-Ala3-X or X-DL-Ala3) branches. The results also indicate that the tendency to form an ordered structure is determined by the identity and the position of the chiral amino acid X (Phe or Leu) in the side chain. PMID- 2597734 TI - DNA backbone flexibility and the Z access for phosphodiester linkage: a quantum molecular approach. PMID- 2597735 TI - Complete 13C resonance assignments of tryptophan in L-lysyl-L-tryptophyl-L-lysine by single-bond and multiple-bond correlated 1H-13C two-dimensional NMR. PMID- 2597736 TI - Vibrational free energy, entropy, and temperature factors of DNA calculated by a helix lattice approach. AB - The vibrational contribution to the free energy, entropy, and the temperature factors of the different atoms in the unit cell are calculated using the method of helix lattice dynamics for the DNA homopolymer poly(dG.poly(dC) in the B conformation. These results are compared to other theoretical calculations and the temperature (B) factors are compared to experiment as well. The problems encountered in using small molecule approximations to describe B factors in DNA like long chain molecules are discussed and a corrected estimate of the temperature factors are presented. Significant differences are found between the different theoretical approaches as reflected in the results of temperature factor calculations. PMID- 2597737 TI - A CD determination of the alpha-helix contents of the coat proteins of four filamentous bacteriophages: fd, IKe, Pf1, and Pf3. AB - The CD spectra of four filamentous bacteriophages--fd, IKe, Pf1, and Pf3--were analyzed to determine the alpha-helix contents of their major coat proteins. Measured spectra included the 192-nm band so that analyses could be carried out over the full wavelength range of the reference spectra for protein secondary structures available (a) from globular proteins [J.T. Yang, C.S.C. Wu, and H.M. Martinez (1986) Methods in Enzymology 130, 208-269] and (b) from poly(L-lysine) [N. Greenfield and G.D. Fasman (1960) Biochemistry 8, 4108-4116]. Extended analyses were also performed with the addition of the spectrum of a model beta turn to the Greenfield and Fasman reference set, with the spectrum of a short alpha-helix in the Yang et al. reference set, and with an estimate of the spectrum of Trp added to both reference sets. The reference set based on the simple poly(L-lysine) polypeptide, plus a spectrum of a model beta-turn or of Trp, gave reasonably good fits to the measured spectra for all four phages and yielded the largest percentages of alpha-helix. The class I phages--fd and IKe- had large percentages of alpha-helix of 98 +/- 2 and 97 +/- 5%, respectively, while the two class II phages--Pf1 and Pf3--had similar but smaller alpha-helix contents of 83 +/- 6 and 84 +/- 2, respectively. While these alpha-helix contents were within the ranges previously reported from CD spectra of these phages in solution, they were more precise, and they indicated that the coat proteins of the intact phages have CD spectra that are probably modeled better by the reference spectra of polypeptides than by those of globular proteins. PMID- 2597738 TI - A Monte Carlo simulation study of the influence of internal motions on the molecular conformation deduced from two-dimensional NMR experiments. AB - Monte Carlo methods have been used to simulate internal motions of aromatic protons of an oligonucleotide at the nanosecond time scale. Each proton is allowed to fluctuate about its equilibrium position. The longitudinal cross relaxation rates of such a system of spins have been determined by computing the appropriate correlation functions. Then the interproton distances have been deduced according to the procedure generally used in two-dimensional nmr techniques (nuclear Overhauser effect spectroscopy--NOESY) and compared to the true values. The influence of the amplitude A and of the internal rotational diffusion constant Dint characterizing the dynamics of the system has been checked for in-phase and for uncorrelated motions. It is shown that for the investigated models the distances deduced from NOESY experiments may be under- or overestimated, depending strongly on the values of A and Dint. Furthermore, the cross-relaxation rate of a couple of protons is very sensitive to the correlation level of the motions of both protons. PMID- 2597739 TI - NMR studies on the induced denaturation of lysozyme by guanidine hydrochloride in the presence of the inhibitor (NAG)3. AB - The stabilization of the folded conformation of lysozyme, arising from the binding of the inhibitor (NAG)3 against induced denaturation, is demonstrated from the 1H-nmr spectra of the enzyme. The nmr spectra reveal that the binding of the denaturant (GuHCl) to the enzyme is associated with changes in the conformation of the enzyme. The binding site of the inhibitor site C also serves as one of the binding sites of GuHCl. The observation that higher denaturant concentrations are required in the unfolding of Lys-(NAG)3 as compared to free Lys can be explained partly in terms of the existence of a competitive binding to the enzyme involving the (NAG)3 and GuHCl molecules. PMID- 2597740 TI - Secondary structure of a core protein from pig skin proteodermatan sulfate: CD and Fourier transform IR spectroscopic studies in solution. AB - The secondary structure of a 38 kDa core protein from pig skin proteodermatan sulfate (PDS), was investigated in solution using CD and Fourier transform (FT) ir spectroscopy. Both techniques generally have provided complementary data on the secondary structures of proteins. CD spectral analysis has shown that the core protein contains 60% beta-turn and alpha-helical structures, the rest being "unordered" structure. FT ir data do not permit calculation of quantitative contributions of substructures, at the present time, to the overall secondary structure of the core protein. CD spectrum of the intact PDS is similar to the core protein CD spectrum. PMID- 2597741 TI - Secondary structure of pig skin proteodermatan sulfate: a perspective from Raman spectroscopic studies in aqueous solution. AB - Raman spectroscopic studies of pig skin proteodermatan sulfate in H2O are indicative of a well defined secondary structure consisting of alpha-helical, beta-turn, and possibly "random" structures. The above conclusion is surprisingly close to the secondary structure of the "core" protein of pig skin proteodermatan sulfate proposed in the previous paper (V. Renugopalakrishnan et al., Biopolymers 28, 1923-1933, 1989) from FT-IR and CD spectroscopic studies in aqueous solution. PMID- 2597743 TI - The effects of pH on hyaluronate as observed by light scattering. AB - Hyaluronate was investigated over a wide pH range, and at near zero and intermediate ionic strength, using dynamic and total intensity light scattering. Commercially obtained rooster comb hyaluronate was purified, and solutions were prepared in pure water by low-power bath ultrasonication and subsequent filtering. These solutions were of low polydispersity and appeared to contain single molecules of hyaluronate. Despite the absence of added electrolyte, these solutions yielded well-behaved Zimm plots. Increasing ionic strength and changing pH decreased radii of gyration and increased diffusion constants. Except for what appeared to be slow hydrolysis at either extreme of pH, molecular weights remained constant under all pH and ionic strength conditions. Under all solvent conditions investigated, diffusion coefficients increased with decreasing hyaluronate concentration. Unsonicated, lightly centrifuged solutions without added electrolyte were polydisperse, and their light scattering intensity was dominated by what appeared to be stable hyaluronate aggregates. The results are interpreted in terms of the polyelectrolyte properties of hyaluronate and its tendency to form stable entanglements, especially at low ionic strength. Previous light scattering studies in the literature on hyaluronate have shown widely varying results. The present article briefly reviews this literature and attempts to explain the variation among the previous results, emphasizing the Kuhn statistical segment length as an indicator of whether results are influenced by polydispersity or contaminants causing hyaluronate aggregation. PMID- 2597742 TI - Probe diffusion in cross-linked actin gels. AB - The diffusion of monodisperse polystyrene latex spheres (PLS) in column-purified 0.65 mg/mL actin solutions, polymerized with 100 mM KCl in the absence and presence of a cross-linker, actin binding protein (ABP), has been studied using dynamic light scattering. Measurements over a wide range of scattering angles from 90 degrees to 8 degrees, corresponding to inverse scattering vector probing distances of about 40-400 nm, respectively, give a measure of both the fraction of PLS mobile over the probing distance (from the normalized time autocorrelation function amplitude) and the average diffusion coefficient of the mobile PLS. Both 100- and 500-nm diameter PLS are fully mobile in polymerized actin solutions over distances of less than 100 nm, as reported previously (Newman, J., Schick, K. S. & Gukelberger, G. Biophys. J. 53, 573a, and Newman, J., Mroczka, N. & Schick, K. L. Biopolymers, 28, 655-666). At increasing probing distances, or when ABP is added at molar ratios of 1:750 or 1:150, greater fractions of the PLS are immobilized, up to almost 99% at the conditions of a 400-nm probing distance with 500-nm probes and at a ratio of 1:150 added ABP to actin. The degree of immobilization correlated well with the amount of added ABP, the size of the PLS, and the probing distance. At increasing probe distances, as the degree of immobilization increases, the remaining mobile fraction of PLS has an increasing average diffusion coefficient. These results suggest a range of pore sizes in the actin gels with a mean size of a few hundred nanometers. PMID- 2597744 TI - Vibrational CD studies of the solution conformation of simple alanyl peptides as a function of pH. AB - The CH-stretching vibrational CD (VCD) spectra of glycyl-L-alanine, L alanylglycine, and L-alanyl-L-alanine have been studied at neutral, high, and low pH in D2O solution. The intense positive VCD band attributed to the C alpha H stretch of the alanyl residue in glycyl-L-alanine at neutral pH is absent in L alanylglycine. In contrast to the VCD spectra of L-alanine, the positive methine stretching VCD band in glycyl-L-alanine and L-alanyl-L-alanine is still present at pH 2. Based on the ring current mechanism, the VCD spectra are consistent with the presence of a five-membered CO...HN intramolecular hydrogen-bonded ring between the C-terminal carboxylate and peptide NH groups at neutral and high pH; and a seven-membered COH...O = C hydrogen-bonded ring between the C-terminal carboxyl OH and peptide C = O groups at low pH. In the N-terminal alanyl residue, the peptide C = O group is hydrogen bonded to the NH trans to the methine bond. The CH-stretching VCD spectra of L-alanyl-L-alanyl-L-alanine at neutral pH are consistent with two intramolecularly hydrogen-bonded conformations for the central alanyl residue. PMID- 2597745 TI - [Control of conduction of afferent impulses across the lateral geniculate body by the side of the superior colliculus in alert rabbits]. AB - On alert rabbits it was shown that the stimulation of the superior colliculus inhibit visual evoked potential both of the ipsi- and contralateral geniculate body. Besides, the suppression of amplitude of the contralateral geniculate body's evoked potential was more significant than amplitude of the ipsilateral geniculate body's evoked potential. On the basis of the obtained results the authors suppose that superior colliculus is involved in organization of the effect of saccadic suppression of lateral geniculate body's visual responses. PMID- 2597746 TI - [Intake of water and sodium chloride solution by the rats after central administration of litorin and immunization with litorin-bovine serum albumin conjugate]. AB - Central injection of litorin suppressed water and sodium chloride solution intake, and also decreased the preference of saline of unrestrained rats during 1 hour test. Active immunization of animals with litorin-bovine serum albumin conjugate led to the augmentation of their daily saline preference. Immunized rats increased also avidity to salt after deprivation, though the consumption volume of liquids decreased. The data, obtained on the immunized animals prove the importance of definite level of endogenous bombesin-like peptide in the salt appetite of rats. The central effect of litorin is discussed in the aspect of changing by it the evaluation of gustatory information. PMID- 2597747 TI - [Microcirculation in the pulmonary vessels during artificial ventilation of different frequencies and volumes]. AB - In acute experiments on cats with closed chest by means of biomicroscopic method it has been shown that artificial ventilation of increased frequency or volume causes the decrease of diameters of arterioles, venules, wide capillaries and also the decrease of the length of functional narrow capillaries. The constriction degree of arterioles and venules depends on their initial diameter. The length of the functional narrow capillaries is being changed to the great extent under frequency increase. Decrease of the volume of the artificial ventilation causes differently directed changes of these parameters in various regions of the lungs. It is supposed that other neuro-humoral factors take part in the realization of the determined changes except alveolar pressure. PMID- 2597748 TI - [Effects of large and small doses of vitamin E on the excitability of frog myocytes]. AB - The effect of the fat-soluble vitamin E on electrophysiological characteristics was investigated on frog cardiomyocytes. Large and small doses of vitamin E produced qualitatively identical effects: shortening of the plateau and decrease of the AP--duration. We assume that large doses of vitamin E can affect the cardiomyocytes membrane transport function, mainly due to the activation of slow membrane channels. PMID- 2597749 TI - [The nature of factors inactivating postural asymmetry factor at the initial stages of compensatory reconstruction in animals with unilateral lesions of the motor neocortex]. AB - The disappearance of posture asymmetry factor activity in the CSF after three weeks of unilateral removals of the neocortex motor region is caused by inactivation factors (IF), which are thermolabile proteins with m.v. about 80 kD and 150 kD. One of IF (150 kD) interacted with protein A which shows its immunoglobulin++ nature. PMID- 2597750 TI - [Changes in evoked cortico-motor responses in the rat during aging and after partial decortication]. AB - Some changes of the organization of cortical motor representations, which were revealed by means of the intracortical microstimulation (ICMS) in aged rats after unilateral partial decortication, were true consequences of the decortication, but had no significant relationship to the aging. Distributions of latent periods of contralateral hind-leg EMG-responses to the ICMS had no significant shifts both during aging and after the surgery. Values of short-latency responses of ipsilateral proximal and axial muscles to the ICMS were in late time periods, from 8 to 16 months after surgery, significantly lower than ones of contralateral homonymous muscles. It is supposed, that ipsi- and bilateral short-latency responses to the ICMS in proximal and axial muscles of operated rats during late time periods are relayed through some pathways from the brain stem to the spinal cord. PMID- 2597751 TI - [Changes in the lungs in the early period of closed trauma of the thorax in rats]. AB - In experiments on rats it has been demonstrated that in the acute period of uninjured parts of the lungs periodic changes of protein, lipid and glucose concentrations developed. In uninjured parts of the lungs one can observe more concentration of lipids and in injured parts-more glucose. The changes of substrates, concentrations in the lungs are due to not only the changes of venous blood excess in the lungs, but are connected with metabolic changes in the cells of the injured and uninjured parts of the lungs. The metabolic changes in the lungs in the acute period of chest trauma influence the creation of such indices of gas exchange as PaCO2 and PACO2. PMID- 2597752 TI - [Antipyrogenic properties of oxytocin]. AB - Effects of oxytocin on pyrogenal or endogenous pyrogen-induced fever were studied. Intramuscular injection of oxytocin (0.2 micrograms/kg every half an hour) did not significantly affect the pattern of pyrogenal-induced fever. Constant intravenous injection of oxytocin (0.4 and 4 micrograms/kg/h) 2-4.5 h after pyrogenal decreased the rectal temperature, on an average, by 24% and 31%, respectively. Endogenous pyrogen fever was not attenuated by intravenous oxytocin (4 micrograms/kg/h). The antipyrogenic effect of oxytocin is related to inhibition of endogenous pyrogen synthesis rather than to blockade of its action, which is indicated by a decreased second peak of the temperature curve, inhibition of endogenous pyrogen synthesis in vitro, and persistence of the hyperthermic effect of endogenous pyrogen. PMID- 2597754 TI - [Cholinergic mechanisms in the development of hydrolysis-transport function of the small intestine during ontogeny of intact and stress-exposed rats]. AB - The blockade of peripheric m-cholinoreceptors by atropine in early periods after rat birth is shown to delay the further development of intestinal transport and also hydrolysis-transport mechanisms for carbohydrates. PMID- 2597755 TI - [Age specificity of lipid fluidity in the sarcoplasmic reticulum of the rat heart]. AB - The lipid fluidity in heart sarcoplasmic reticulum membranes prepared from adult (12 mo.) and old (24 mo.) rats has been measured by the fluorescence probe (DPPH) and spin probe (5NS) methods at 22 and 37 degrees C. The lipid fluidity in the old rat membranes is higher than that in the adult rat ones. It has been suggested that this difference is caused by age lowering in reliability of membrane fluidity stabilization systems. PMID- 2597753 TI - [Effects of several regulatory peptides on the functional activity of the pancreas in acute experimental pancreatitis]. AB - The influence of regulatory peptides (somatostatin, calcitonin, and dalargin) on xanthine oxidase activity and lipid peroxidation level in pancreatic tissues as well as on the release of pancreatic enzymes (alpha-amylase, trypsin, lipase, and transamidinase) into blood was studied in 205 rats with experimental acute pancreatitis. Somatostatin and dalargin were shown to have obvious antioxidant effect seen by reduced xanthine oxidase activity and MDA level. All studied peptides stimulate reduced release of pancreatic enzymes. Particularly, reduction of dalargin and somatostatin is caused by inhibition of their synthesis as well as by pancreas protective effect of the peptides. Release of enzymes reduced by calcitonin is probably associated only with inhibition of secretory activity of the pancreas. PMID- 2597756 TI - [Pathogenesis of porphyrin-sensitized lethal and sub-lethal photo-injury]. AB - By means of morphological methods the mechanisms of thanatogenesis were studied in 57 white mice after the hematoporphyrin derivative administration and xenon lamp radiation imitating the sun spectrum. In dependence of integrative doses of sensitized photoradiation and individual resistance of the organism there was observed immediate (hours), retained (days) and remote (weeks) death of animals. In the first two groups death came as a result of photocoagulation of plasma proteins and toxemic shock with liver, lung and brain injury, and in the third group--as a result of suppurative resorptive intoxication against the background of ulcerous skin necrosis. PMID- 2597757 TI - [New methodical approach to the study of platelet aggregation in vitro]. AB - A new approach to the investigation of the kinetics of platelet aggregation is described. The method is based on the analysis of light transmission fluctuations produced on the changes in the number of platelets in optical channel. The relative dispersion of the fluctuations of transmitted light intensity was used as a parameter to estimate the degree of platelet aggregation. Application of this method for the analysis of platelet aggregation permits to get new information about this process. PMID- 2597758 TI - [Dynamic radiothermography of the human liver]. AB - In the experiments on the volunteers it has been shown that the method of dynamic radiothermography is quite sensitive for measurement of temperature fluctuations in human body. This method makes it possible to register the changes of the temperature in inner organs using the probes placed on body surface. Some volunteers drank hot or cold water, some volunteers drank glucose solution, others got the dose of low laser radiation upon the liver. In the case of cold water liver temperature fell, in all other cases liver temperature rose. The results of the dynamic radiothermography of human liver allow us to suppose that low laser radiation of this organ leads to the stimulation of liver blood flow. PMID- 2597759 TI - [Effects of morphine and naloxone on pain sensitivity after radiation injuries in rats]. AB - Radiation in doses 150 Gy induces different changes in pain sensitivity in rats by thermal (analgesia) and electrical (hyperalgesia) stimuli. Naloxone (0.1 and 1 mg/kg) and morphine (5 mg/kg) show, that analgesia is realized due to opioid mechanisms. PMID- 2597760 TI - [Opioid peptides, regulators of acetylcholinesterase activity]. AB - Studies have been made on the opioid peptides--enkephalins their fragments, and alpha- and gamma-endorphins with concentrations of 10(-8)-10(-4) M, on acetylcholinesterase of human blood erythrocytes. It was found out that these peptides, which were fragments of one propeptide beta-LPH were reversible effectors of acetylcholinesterase. Enkephalins and a number of their fragments were noncompetitive inhibitors. It was shown that natural pentapeptide has the highest inhibitor activity; decreasing of inhibitor activity or the absence of it was a result of pentapeptide molecules degradation. Short endorphins were noncompetitive activators of acetylcholinesterase. PMID- 2597761 TI - [Modification of selective adsorption of muscarinic antagonists in cerebral membranes during chlorophos poisoning]. AB - Using radioligand assay it was demonstrated that chlorophos intoxication produced inhibiting effect on the kinetics of membrane binding of 3H3 quinuclidinylbenzilate and 14C-cyclosil in the brain. Cholinesterase reactivator dipyroxime was shown to induce normalization of the cyclosyl specific binding kinetics. It seems to be justified to propose that cooperative action of cholinolytic agents and cholinesterase reactivator at the level of m cholinoreceptors in the course of intoxication may be one of the mechanisms of the potentiation of therapeutic effects of these drugs. PMID- 2597762 TI - [Anti-necrosogenic action of natural and synthetic antioxidants in coronary occlusive myocardial infarct]. AB - The synthetic liposoluble antioxidant BAT. 120 mg/kg, was found to produce markedly protective effects in a rat model of coronary occlusive myocardial infarction, whereas the water soluble BAT analogue, 4-Oxy-3,5-ditretbutylphenyl phosphonic acid sodiate (SFN-6), 100 mg/kg, displayed no protective effects. The natural antioxidant beta-carotene capable of displaying antioxidative activity at low partial O2 pressures was shown to reduce the size of postinfarct scar by 34% when given in a dose of 20 mg/kg. The synthetic antioxidants, BAT and SFN-6 given in doses of 100 to 120 mg/kg each decreased antioxidant enzyme activities in the intact or infarct-related myocardium. beta-carotene was found to lack inhibitory effects on the myocardial antioxidant enzymes, thus enhancing its cardioprotective properties. PMID- 2597764 TI - [T-lymphocyte induced normalization of transformed malignant fibroblasts: lymphokine with normalization factor activity]. AB - Normalizing influence of different lymphocyte populations and their soluble factors on L-929 transformed malignant fibroblasts (L cells) has been examined. It was demonstrated that splenic T-lymphocytes caused stable (heritable) normalization of receptor apparatus, biophysical and proliferative characteristics of L cells. Lymphokine with the activity of normalization factor (NF) was purified from 24-hour immunocyte conditioned medium. Stability of the normalization phenomenon was caused by NF induced synthesis of functionally analogous factor in L cells. The results obtained indicate the existence of non cytotoxic mechanisms of tumour growth immunological control. The isolated lymphokine possessed also the activity of early embryonal cell differentiation factor. It is suggested that lymphokines with the activity of NF are physiological regulators of nonlymphoid cell differentiation. PMID- 2597763 TI - [Use of synthetic analogs of enkephalins as antiatherogenic means]. AB - The experiments have been performed on 70 male rats weighing 200-250 gr., 53 patients with obliterating atherosclerosis of lower extremities have been examined. Leu-enkephalin analogues (dalargin and DEFN) administration in a dose of 0.1 mg/kg has been determined to decrease cholesterol levels in the blood in acute and chronic experimental hypercholesterolemia. The use of pharmacological preparation -- enkephalin analogue of dalargin in complex treatment of the obliterating atherosclerosis of lower extremities leads to cholesterol concentration decrease, parathormone concentration decrease in the blood of patients and hyperlactatemia decrease in venous blood of the damaged extremity. Leu-enkephalin analogues, action mechanisms and the possibility of their use for atherosclerosis treatment is discussed. PMID- 2597766 TI - [Specificity of the location of human chromosomes in the nucleus of a moving cell]. AB - Data are presented on the distribution of centromeric heterochromatin of the human X-chromosome in the interphase nucleus of a moving cell. The in situ hybridization made it possible to obtain some results leading to the following conclusions: in moving fibroblasts centromeric heterochromatin of the X chromosome is located in end regions of the interphase nucleus; there was no preferential localization noted of the centromeric region of the X-chromosome in the front or back areas of the nucleus as to the direction of the movement. PMID- 2597765 TI - [Evaluation of antileukemic activity of L-lysine-alpha oxidase from Trichoderma sp. in chemotherapeutic experiments]. AB - Evidences on the antileukemic effect of L-lysine alpha-oxidase from Trichoderma sp. are presented. It is inferred that enzyme needs detail studying as a potential chemotherapeutic drug both in experimental and clinical research. PMID- 2597767 TI - [Endogenous colony formation in closed craniocerebral trauma in mice]. AB - The model of closed brain trauma in mice using stem hematopoietic cell cloning methods has shown inhibited endogenous spleen colony formation and reduced number of reticulocytes in blood circulation during early periods subsequent to traumatic procedure. Maximal inhibition of bone marrow function occurs 4 days after trauma and is accompanied by a dramatic reduction of thymus weight and cellularity. The observed changes in bone marrow function can be one of the important factors leading to lower resistance of the organism to infections during early periods after brain trauma. PMID- 2597768 TI - [Changes in amino acid metabolism at the onset of colchicine resistance in Dzungarian hamster fibroblast cell culture]. AB - We have studied amino acid up-take from incubation media by colchicine-resistant and colchicine-sensitive Djungarian hamster fibroblast cells. It has been shown that arginine and asparagine amino acid contents in the medium are different for colchicine-sensitive and colchicine-resistant cells. Amino acids concentration is not reduced in the medium after incubation of resistant cells, while it is decreased after incubation of sensitive cells. We can suggest that penetration of low-weight sources of nitrogen into sensitive cells is hampered. It can also be suggested that protein macromolecules are the main source of nitrogen for these cells. The protein up-take levels from the incubation medium, as assessed by the ammonia and amino acid contents of cell counts don't exceed 5% of their initial concentrations in the medium. PMID- 2597769 TI - [Phospholipase A activity determines the rate of respiration of the mitochondria in hibernating animals]. AB - The mechanisms for regulating the rate of respiration and oxidative phosphorylation in liver mitochondria from hibernating ground squirrels were studied. The microviscosity of the mitochondrial membrane in hibernating squirrels was found to be higher than that in active animals. Probably, a high microviscosity of the membrane causes a decreases in the rate of the transport of oxidation substrates into the mitochondrial matrix, which in turn may be one of the main reasons for the inhibition of mitochondrial respiration in hibernating squirrels. The activation of phospholipase A2 in a hypotonic medium results in the acceleration of the respiration and phosphorylation in the mitochondria from hibernating squirrels and is accompanied by the increase of the transport of substrates across the mitochondrial membrane. The inhibition of phospholipase A2 decreases Ca2+--induced acceleration of the transport of substrates and prevents the activation of the respiration and phosphorylation in a hypotonic medium. PMID- 2597770 TI - [Characteristics of crossed resistance of neoplastic cells with high level of colchicine resistance]. AB - Using a long-term selection the authors obtained the cells of a hamster with a rather high level of stability to colchicine (800-16,600 times). The nature of resistance of these cells to actinomycin differed from those having general origin with the newly obtained but having a lower level of stability to colchicine. This level of stability did not correlate with that to a selective agent. PMID- 2597771 TI - [Apoptosis and regeneration of the gastric mucosa under the action of S-phase specific agent, hydroxyurea]. AB - The treatment of periodic injections of hydroxyurea to mice on the processes of regeneration in gastric mucosa was studied. In all experimental groups of animals dystrophic and atrophic changes of gastric mucosa could be observed. The phenomena of dystrophy were more pronounced. If the time of the experiment was not more than 4 days apoptosis bodies could be found only in the epithelium. The long-term duration of the experiment resulted in increased death of apoptosis bodies inside the glands, and development of atrophy of gastric mucosa. PMID- 2597772 TI - [Changes in the hemostasis and fibrinolysis system in rats with experimental renal hypertension]. AB - The arterial renal hypertension (170-180 mm Hg compared to the norm 100-120 mm Hg) developed in 2 months after one side nephrectomy and partial occlusion of the other renal artery. The level of high molecular weight plasma proteins was raised which led to the increase in the peripheral vessel resistance and hypertension degree. Fibrinolysis was depressed in the blood and in the cortical zone of the kidney. In early stages of hypertension fibrinolysis was sharply elevated, and high molecular weight compounds content was decreased. The antithrombin III and nonenzymatic fibrinolysis level were increased during the whole period (10-150 days). PMID- 2597773 TI - [Characteristics of tubulo-stromal relationships in the kidneys of normal rabbits and humans]. AB - Extraglomerular cortex and medulla structural elements of kidneys, obtained from 10 male normal rabbits and 10 human beings (8 male and 2 female), who died from accidents at the age of 16-40 years, were studied in comparison. Morphometric studies with statistical evaluation are presented in diagrams, showing the percentage correlation of structural elements of rabbit and human kidneys. It is shown that the difference in life conditions of the studied species may result in the difference of these correlations The obtained results must be taken in to account in the comparative study of pathologic processes in the human and rabbit kidneys. PMID- 2597774 TI - Polycythemia vera. A clinical study of 141 patients. AB - The clinical course of 141 unselected patients (64 m, 77 f, median age 59) with polycythemia vera (PV), treated during the period 1967 to 1986 was analyzed to study prognostic factors and the correlation between treatment strategies and complication rates. Therapy was performed according to a prospectively defined treatment protocol. Primary control of the disease was achieved by phlebotomy. Marrow suppression by radioactive phosphorus or low dose busulphan was used only as a second-line therapy or to lower high platelet counts. The clinical course of the patients was characterized by a low rate of acute leukemia (4%) and a high rate of thromboembolic complications (40%). Myelofibrosis developed in 17 patients (12%). Median survival of the patents was 9.4 years. The prognostic influence of several parameters at the time of diagnosis was tested: age, sex, spleen size, percentage of blood blasts + promyelocytes, leucocyte count, platelet count, hemoglobin, hematocrit, reticulocyte count and the values of the lactate-dehydrogenase (LDH) and the alkaline neutrophil phosphatase (ANP) all had no significant influence on the length of survival. The prognosis of PV patients with atypical disease presentation at diagnosis was not different from patients with typical disease. PMID- 2597775 TI - Severe neutropenia associated with large granular lymphocyte lymphocytosis: successful control with cyclosporin A. AB - Lymphocytosis of large granular lymphocytes (LGL) with severe neutropenia was diagnosed in a 42-years old patient. After prednisone yielded only a transitory effect, long lasting improvement was achieved by treatment with cyclosporin A. PMID- 2597777 TI - The molecular biology of coagulation. PMID- 2597776 TI - Chronic myelogenous leukemia following radiation therapy for testicular seminoma. AB - A 43-year-old man was treated with orchiectomy and radiotherapy for testicular seminoma. Four years later, he developed a typical Philadelphia chromosome positive chronic granulocytic leukemia. Since the patient was not eligible for bone marrow transplantation, he was treated with busulfan. Long term follow-up of patients who received radiotherapy for testicular seminoma is warranted in order to detect possible secondary tumors. PMID- 2597778 TI - Perimenstrual symptoms: relationships with chronic stress and selected lifestyle variables. AB - Of primary interest in the present study was the assessment of the association between several contextual factors, including chronic stress, exercise, alcohol, nicotine, and caffeine intake, and the self-report of perimenstrual symptoms. Two hundred and eleven women completed questionnaires designed to assess chronic stress, perimenstrual symptoms, and physical health. The results indicated that stress accounted for a significant amount of the variance in perimenstrual symptoms. Stress, however, accounted for a substantially greater amount of variance in scores on a general health measure than in self-reports of perimenstrual symptoms. Of those lifestyle variables assessed, only duration of current level of strenuous exercise was associated with perimenstrual symptoms to a meaningful extent. PMID- 2597779 TI - Intrafamilial patterns reported by young type A versus type B males and their parents. AB - Retrospective reports regarding parent-child and parent-parent relations during the childrearing years were obtained from adult informants. Male undergraduates typed as As or Bs completed the Clarke Parent/Child Relations Questionnaire augmented with items of likely relevance to A/B. Parallel data were obtained from a subset of subjects' fathers and mothers. Type A and B groups were not different on numerous variables, including parental aggressiveness, vague or escalating standard-setting, or work orientedness. Type A sons were more inclined to view their fathers as attaching great importance to achievement, as setting hard-to meet expectations, as being unimpressed with son's achievements, and as relating in a competitive way. Differences regarding sons' perceptions of mother were less marked. It is not yet clear to what extent these perceptions (particularly the sons' perceptions of their fathers) are accurate and may thus have played a role in the development of A/B differences, or instead represent a son's judgmental biases associated with his A/B status. PMID- 2597780 TI - Glycosylated hemoglobin levels and self-reported stress in adults with diabetes. AB - This study examined the relationship between glycosylated hemoglobin and self reported stress in a sample of adult Type II diabetics. The study sample was drawn from participants in a randomized clinical trial of the comparative effectiveness of two oral antihyperglycemic drugs in the treatment of non-insulin dependent diabetes. The 19 study participants were asked to complete a brief questionnaire on recent stress. Stress scores were then compared with levels of glycosylated hemoglobin. Correlations between glycosylated hemoglobin and stress scores were highly significant, a finding of particular clinical relevance in view of the relatively small number of participants. These findings suggest that sustained stress may contribute to poor glucose control in diabetics. Individuals interested in stress-related research may find glycosylated hemoglobin a useful marker of physiological stress. PMID- 2597781 TI - The relationship between hostility and blood pressure in children. AB - The relationship between two dimensions of hostility and resting blood pressure was examined in 98 children aged 7 to 10 years. The children completed the expressive and experienced hostility subscales of the Buss-Durkee Hostility Inventory and one week later had blood pressure and obesity levels assessed. Multiple regression analyses and analyses of variance showed that expressive hostility was positively associated with blood pressure, although this relationship became marginally significant when the effects of obesity were controlled. A significant inverse relationship was found between experienced hostility and systolic blood pressure. These results are discussed as they relate to findings in adults on hostility and cardiovascular disease and the relationship between hostility, blood pressure, and obesity. PMID- 2597782 TI - Salivary IgA is a weak stress marker. AB - Several studies support the hypothesis that psychological stress may negatively affect immunocompetence. The present study sought to determine whether a relationship can be established between a measure of psychological state of stress and level of immunoglobulin of the A class (IgA) in saliva. To this end, 44 dentistry students were tested on four occasions; two occasions were stress inductive (examination situation), and two occasions were free of any academic stressor. At each session, the participants were asked to fill out the stress rating instrument, and unstimulated whole saliva samples were obtained. Salivary IgA was measured by a microplate Enzyme Linked Immunosorbent Assay (ELISA). A significant difference in the level of salivary IgA was observed only for the most polarized contrast, ie, between final exam and end of summer vacation (p less than .01). A weak negative correlation between the level of salivary IgA and the stress rating was observed (r = -0.25) only at the final exam. Our results suggest that assaying immunoglobulin A in saliva to measure stress may not be as useful in psychophysiological research as expected. PMID- 2597783 TI - Methods for assessing fieldworker hand exposure to pesticides during peach harvesting. PMID- 2597784 TI - Soil adherence to human skin. PMID- 2597785 TI - Organochlorine residues in Baluchistan/Pakistan: blood and fat concentrations in humans. PMID- 2597786 TI - Survey of barium in Italian drinking water supplies. PMID- 2597787 TI - Clam burrowing bioassay for estuarine sediment. PMID- 2597788 TI - Cadmium and lead accumulation by goldfish exposed to aqueous refuse incinerator fly ash leachate. PMID- 2597789 TI - Effects of chromium and cadmium upon respiration and survival of Callinectes similis. PMID- 2597790 TI - Effects of lead on the spawning potential of the fresh water fish, Anabas testudineus. PMID- 2597791 TI - Distribution of polycyclic aromatic hydrocarbons (PAH's) in marsh sediments, Iraq. PMID- 2597792 TI - Toxicological aspects of activated sludge feeding. PMID- 2597793 TI - 3H-PDBu binding after administration of methylmercury to mice. PMID- 2597794 TI - Chronic toxicity of phosalone to rats: effect on erythropoiesis. PMID- 2597795 TI - Fluoride residues in frozen foods fumigated with sulfuryl fluoride. PMID- 2597796 TI - Effects of convection-oven and microwave-oven drying on removal of alachlor residues in a fabric structure. PMID- 2597797 TI - Water hyacinth as indicator of heavy metal pollution in the tropics. PMID- 2597798 TI - Cadmium concentrations in beef consumable tissues in relation to age of animals and area of their breeding. PMID- 2597799 TI - Metabolism of chlorfenvinphos in both soil and plant of cauliflower and brussels sprouts field crops. PMID- 2597800 TI - Fluorescein diacetate hydrolysis for determination of accelerated degradation of thiocarbamate herbicides. PMID- 2597802 TI - There is no convincing evidence for a relationship between cigarette advertising and consumption. AB - A recent New Zealand study can be challenged on the grounds of inadequate theorization, questionable modelling and operationalization, and the ignoring of contradictory data. Therefore, its public-policy implications in terms of curbing or banning tobacco promotion are highly dubious. PMID- 2597801 TI - Dinoseb presence in agricultural subsurface drainage from potato fields in northwestern New Brunswick, Canada. PMID- 2597803 TI - The effects of tobacco advertising on children. AB - The London Based Children's Research Unit (CRU) has investigated juvenile smoking initiation and advertising in 15 countries. Each country investigated differed with respect to tobacco advertising restrictions, ranging from Norway, which has had a long-term ban on all advertising of tobacco products, to Hong Kong and Japan, which had few advertising restrictions at the time of the research. Advertising was not found to significantly influence juvenile smoking initiation and it was also found to be a poor predictor of juvenile smoking prevalence. That is, countries with tobacco advertising did not have a higher level of juvenile smoking prevalence than countries without advertising. PMID- 2597804 TI - The influences of advertising on tobacco consumption: comments on Boddewyn & Chapman. PMID- 2597805 TI - Syringe exchange schemes: a report and some commentaries. PMID- 2597806 TI - The U.S. general population's experiences of responding to alcohol problems. AB - Respondents in a 1984 national adult sample report on the experiences of treatment for alcohol problems, of talking to someone about an alcohol problem of their own, and of others' suggestion that the respondent cut down. Most who have been treated (3.4% on a lifetime basis, 1.3% within the last year) have also encountered informal pressures. A majority of respondents have pressured others to cut down their drinking; such efforts do not appear to be clustered in a few 'control specialists', and heavier drinkers are about as likely as lighter drinkers to pressure others. Within the family, the flow of pressure is from older to younger generations, and from women to men, but a heavy-drinking woman is as likely to be pressured as a heavy-drinking man. Somewhat more men than women report applying pressure on friends. PMID- 2597807 TI - The prevalence in various social groups of eight different drinking patterns, from abstaining to frequent drunkenness: analysis of 10 U.S. surveys combined. AB - Ten surveys of drinking in the U.S.A. were combined, producing a sample size of 12,603 cases. The present study uses only non-Hispanic Black and White races, bringing the total number down to 9891. Eight drinking categories were used, the heaviest being those who drank at least eight drinks at least three times a week. Classification by sex, age, race and socio-economic status produced 72 social subgroups. The distribution of drinking patterns varied a great deal in these subgroups; frequent light drinkers, for example, were 0% in one subgroup and 42% in another; abstainers were 0% in one group and, in another, 76%. The type of classification of 'heavier' drinkers so often used in surveys of small sample size, where the lower limit of amount of drinking is unrealistically low, may give a false impression of the distribution of drinking patterns. We found that the proportions of respondents falling into our categories 1, 2, 3 and 4 (corresponding to many definitions of 'heavier' drinkers) are not good predictors of frequent drunkenness, or of serious problems. PMID- 2597809 TI - Psychological profile of social drinkers. AB - In a cross-sectional study, the psychological profile of light social drinkers was compared with that of heavy social drinkers and alcohol-dependent patients who showed no evidence of clinical depression. The selection of psychological tests was based on the hypothesis that alcohol abuse and depression may sometimes be different expressions of the same disorder, and that the relationship between the two disorders may in part be explicable in terms of shared psychological vulnerability factors. The tests chosen were those thought most likely to predict vulnerability to depression. Dependent patients demonstrated significantly greater distortion of cognitive style than heavy social drinkers, who in turn rated significantly higher than light drinkers. Heavy social drinkers occupied a middle ground with regard to psychological profile between light drinkers and 'alcoholics', sharing some attributes with each. Possible implication for interventions by general practitioners are discussed. PMID- 2597808 TI - A randomized study of secondary prevention of early stage problem drinkers in primary health care. AB - The subjects were recruited from participants in a health examination of random samples of the adult population in Stockholm county. Those aged 18-64 years who admitted a high alcohol consumption (greater than 40 g 100% ethanol/day) among men and greater than 30 g among women) or had an elevated value of serum gammaglutamyltransferase (GGT) (cut-off point 1.0 microkatal/l for men and 0.6 microkatal/l for women) or had certain other indications of a high alcohol consumption were included. More severe cases, and those with an elevated GGT due to reasons other than alcohol, were excluded. The remaining subjects, 70 men and 13 women, were allocated at random to either an intervention or a comparison group. An elevated GGT was the main inclusion criteria. The subjects in the comparison group were advised by the general practitioner to cut their alcohol consumption, while those in the intervention group made further visits to their general practitioner, who gave general support and used an elevated GGT as an indication of the recent level of alcohol consumption at consecutive visits. There were three visits on average, so we are comparing a group receiving advice with a group receiving further minimal intervention. At the one-year follow-up there were greater, however not significant, reduction in GGT-level, in self reported alcohol consumption and in a 'problem index' in the minimal intervention group than in the comparison group. PMID- 2597810 TI - Alcoholism among outpatients of a rural district general hospital in Kenya. AB - This article presents the results of a study of alcoholism among outpatients of a rural district hospital in Kenya. One hundred and twelve outpatients aged 18 years or over attending Kisii District Hospital were interviewed using the alcohol section of the Diagnostic Instrument Schedule (DIS). The participants consisted of 56 males and 56 females. Of these, 54% of the males and 25% of the females met the DIS criteria for alcohol abuse and/or alcoholism. Those classified as alcoholics differed significantly from the non-alcoholics on variables associated with sex, age, past marital state, religion and types of alcoholic drinks consumed. No significant differences were found with respect to present marital state, education, occupation, family size, age of first intoxication or physical illness. PMID- 2597811 TI - Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). AB - A shortened 10-item scale for clinical quantitation of the severity of the alcohol withdrawal syndrome has been developed. This scale offers an increase in efficiency while at the same time retaining clinical usefulness, validity and reliability. It can be incorporated into the usual clinical care of patients undergoing alcohol withdrawal and into clinical drug trials of alcohol withdrawal. PMID- 2597812 TI - The Minnesota Model. PMID- 2597813 TI - Resisting temptation: a psychological analysis. PMID- 2597814 TI - HIV spread among drug addicts in the Federal Republic of Germany. PMID- 2597815 TI - Emergence of buprenorphine dependence. PMID- 2597816 TI - Why don't we take adequate drinking histories from elderly admissions? PMID- 2597817 TI - Drugs, alcohol and crime. Abstracts of the Society for the Study of Addiction to Alcohol and Other Drugs annual symposium. 16th and 17th November 1989, Leicester. PMID- 2597818 TI - Human excimer laser keratectomy. Short-term histopathology. AB - The first human trial utilizing the argon fluoride excimer laser at 193 nm to produce a superficial keratectomy in the initial three of 10 human eyes has been described with the clinical appearance and short-term (less than 14 days) histopathologic evaluation of these three eyes. The process of laser superficial keratectomy has proved one of the promising areas of surgical intervention for reconstructive or refractive keratoplasty in the future. Intensive investigations of corneal wound healing following laser ablation as well as the nature and long term stability of the corneal excisions or induced refractive corrections are needed. It is essential that the optimal laser parameters be established for the various refractive corrections and other corneal surgical techniques and that pathophysiologic and histopathologic changes that have been induced by the excimer laser-corneal tissue interaction in animals and humans be critically and extensively analysed. PMID- 2597820 TI - Physicians for human rights. PMID- 2597819 TI - The corporate medical department and AIDS. AB - HIV infection in the workplace reflects the dimensions and distribution of the problem in the community at large. Despite this, accommodation of ill employees has been the general pattern and disruptions of any kind the exception. Corporate medical departments can be important participants in the clinical and social response to AIDS. Recognition of the illness itself, collaboration in the provision of health services, referral when necessary for treatment and counselling, assistance with medical benefits, and arranging for appropriate workplace modifications are among ways in which medical departments can assist concerned or ill employees. Confidentiality is essential in all of these interactions. Education of the workforce about AIDS is especially important from a public health as well as from an administrative standpoint. Providing input on relevant corporate policies and in determination of corporate philanthropy can be other dimensions of corporate medical departments' response to AIDS. PMID- 2597821 TI - Are we achieving a balance: time to reconsider? PMID- 2597822 TI - Ethics of the use of fetal tissue. PMID- 2597823 TI - Steroids in meningitis. PMID- 2597824 TI - Alcohol misuse and the hospital doctor. AB - Alcohol misuse among patients attending hospital is common but frequently undetected. Hospital doctors need to take a proper alcohol history in every patient and to recognize symptoms that may result from excessive drinking. Appropriate advice about sensible levels of drinking could then have a beneficial impact on the incidence of alcohol problems. PMID- 2597825 TI - Safer contrast agents? AB - Two recently reported large scale clinical surveys support the impression that the new non-ionic low osmolality iodinated radiographic contrast media are indeed significantly safer for intravascular use than conventional agents. These surveys will lend additional weight to the argument for the universal use of non-ionic agents despite their relatively high cost. PMID- 2597826 TI - How to perform a percutaneous liver biopsy. AB - Liver biopsy is a safe and indispensable tool for the diagnosis and management of many forms of liver disease. Percutaneous techniques are easy to learn and relatively little experience is required to obtain an adequate specimen of liver safely. Most doctors training in general medicine and some training in general surgery and radiology should develop experience with this technique. PMID- 2597827 TI - The MRCPsych examination. PMID- 2597828 TI - MRCPsych Part One: multiple-choice questions. PMID- 2597829 TI - Medical associations and the state. PMID- 2597830 TI - Do politicians understand the needs of postgraduate medicine? PMID- 2597831 TI - Community psychiatry: are we coping? PMID- 2597832 TI - How can we get more donors? PMID- 2597833 TI - Tolerability of simvastatin. PMID- 2597834 TI - The involvement of Soviet psychiatry in the persecution of dissenters. PMID- 2597835 TI - Treatment of severe psychiatric illness in a day hospital. AB - Severity of psychiatric illness was assessed using standardised clinical and social measures in 69 in-patients and 41 day patients admitted consecutively from the community. Day and in-patients differed little in terms of psychiatric symptoms and social disability, especially if compulsory admissions were excluded. Protection of self or others was a common reason for in-patient admission given by clinicians, who were otherwise prepared to treat seriously ill patients in the day hospital. Very few of the day patients had to be transferred to the in-patient facility, and at three months and one year the two groups showed similar improvements. It is concluded that day treatment is feasible for some seriously ill psychiatric patients, but a random-allocation study is required to assess more completely the efficacy of day treatment, and define the characteristics of those who require in-patient admission. PMID- 2597836 TI - Lapse, relapse and survival among opiate addicts after treatment. A prospective follow-up study. AB - This paper presents data from the first British prospective study to investigate relapse among opiate addicts after treatment. Eighty subjects were followed up over the six-month period immediately after discharge from treatment and were interviewed on several occasions. Large numbers of subjects used opiates within a very short time after discharge; 71% used them within the first six weeks. However, this first lapse to opiate use did not herald a full-blown relapse to dependent use. There was a gradual increase in the number of abstinent subjects, with 45% abstinent and living in the community at the six-month point. The practical and theoretical implications may be regarded as broadly encouraging. PMID- 2597837 TI - Circumstances surrounding the initial lapse to opiate use following detoxification. AB - Seventy-eight opiate abusers were followed up after successful in-patient detoxification in order to examine renewed opiate use. The greatest number of initial lapses occurred within a week of subjects leaving in-patient treatment. Eleven categories of lapse precipitant were identified: cognitive, mood, external, withdrawal, interpersonal, leaving a protected environment, drug availability, drug-related cues, craving, priming, and social pressure. Cognitions, negative moods and external events emerged as the most commonly mentioned factors; these often occurred together, either in clusters or in a sequence. Implications of these results for models of relapse and for treatment approaches are discussed. PMID- 2597838 TI - Sex differences in the differentiation of psychiatric symptomatology. AB - A study was conducted using data obtained from the first stage of a community survey in Spain, in which the 60-item version of the GHQ was administered to 1224 adults. Three hypotheses concerning respondents aged under 55 years were tested. The first was that in the context of a principal-components analysis, a greater proportion of the explained variance would be accounted for by the first (general) factor in women than in men. This was supported. The second hypothesis was that the intercorrelations between the GHQ-28 subscales would be greater for women than for men. This was refuted. The third hypothesis was that the differentiation between anxiety and depression would be greater in men than in women. This was supported. The differences investigated were found not to apply among respondents aged 55 years and over. PMID- 2597839 TI - Characteristics of psychiatric hospital absconders. AB - Absence of patients without leave is common in psychiatric hospitals, and causes anxiety to staff, relatives, and the lay public. Such incidents are difficult to predict. This study attempted to identify the characteristics of patients absconding from a UK hospital over one year. Numbers were small, as those patients discharged against advice and failing to return from leave were excluded. Absconders were predominantly male, young, compulsorily admitted, and discharged with a diagnosis of schizophrenia. They tended to be single, had many previous admissions, and a longer total length of stay, and the police were more often involved in their admission. Reasons for absconding and the implications for management of newly admitted psychiatric patients are discussed. PMID- 2597840 TI - Dexamethasone suppression test in dementia and depression. Clinical and biological correlates. AB - To determine the usefulness of the DST in differentiating depression from dementia, the test was administered to three diagnostic groups of psychogeriatric patients: depression; dementia; and dementia with depression. Clinical assessments were supplemented by ratings on the HRSD and SCAG, as well as by EEG and CT. All three groups showed a high incidence of abnormal DST results unrelated to presence or severity of affective symptoms, but showing a better association with SCAG and its 'organic' subsets. The mechanism(s) underlying these abnormal results may reflect organic brain disease. The usefulness of the DST in differentiating depression from dementia in the elderly was not confirmed. PMID- 2597841 TI - An uncontrolled study of cognitive therapy for morbid jealousy. AB - Thirteen patients presenting with morbid jealousy were treated using a cognitive approach adapted from Beck's cognitive therapy for depression. Cognitions in morbid jealousy showed the characteristics of automatic thoughts as described by Beck, and were based on faulty assumptions derived from interpretations of past experiences. The cognitive treatment directed mainly at the faulty assumptions resulted in improvements in ten patients and no change in one; two patients dropped out of treatment. The results are considered encouraging. PMID- 2597842 TI - Life events and hostility in self-poisoning. AB - Life events in 82 self-poisoning subjects were studied using the Bedford College LEDS to see whether there was a difference between those who had a clear depressive syndrome (according to the Present State Examination) and the remainder. Equally high levels of severely threatening events were found in the depressed and non-depressed groups, but the former were older, had experienced more chronic difficulties and had been treated more often in the past for depression. Greatest numbers of life events were found in those with high levels of extrapunitiveness (recorded on the HDHQ), whereas those who had not experienced a severe life event showed predominance of intropunitiveness. Suicidal intent was not related to experience of life events, but has previously been shown to be associated with high intropunitiveness. The findings are discussed in the light of current theories linking life events, depression and parasuicide, and emphasise the need for longitudinal studies to examine these factors in relation to repeated parasuicide. PMID- 2597843 TI - Lithium prophylaxis and expressed emotion. AB - Expressed emotion (EE) in key relatives of 21 patients with bipolar affective or schizoaffective psychoses was assessed by the CFI. All patients had been on prophylactic lithium for at least three years and were without psychotic symptoms at interview. The relationship between relatives' EE status and patients' course of illness was studied both retrospectively and prospectively. Two critical remarks designated high EE. The relatives' EE status was not related to number of hospital admissions or to severity and length of recurrences if the entire period of lithium treatment is considered as a whole. However, patients living with high EE relatives showed a significantly poorer response during the three years before interview, and an even poorer response in the nine-month follow-up. PMID- 2597844 TI - Perceptivity and paraceptivity during measurement of gastric emptying in anorexia and bulimia nervosa. AB - Gastric emptying of a mixed meal was measured in 22 patients with anorexia nervosa, ten with bulimia nervosa and ten controls. Ratings on a visual analogue scale (VAS) were made during the test. Patients with anorexia nervosa felt fuller and less hungry than controls, although satiety was not related to gastric emptying rate, controls showed a correlation of about 0.6 between gastric contents and reported hunger and satiety. Patients with anorexia nervosa had significantly lower correlations between gastric contents and hunger, but normal correlations with fullness. Significant correlations were often observed between gastric contents and symptoms of eating disorder in both anorexic and bulimic groups, but not in controls. PMID- 2597845 TI - 'Normal' eccentrics. PMID- 2597846 TI - Elementary, my dear Freud. PMID- 2597847 TI - Capgras' syndrome. PMID- 2597848 TI - Self-rating. PMID- 2597849 TI - Pre-pubertal depressive stupor. PMID- 2597850 TI - Multiple personality disorder. PMID- 2597851 TI - Lofepramine-induced hyponatraemia. PMID- 2597852 TI - Munchausen syndrome masquerading as AIDS-induced depression. PMID- 2597853 TI - The Glasgow rehabilitation survey. AB - To assess the future requirements for long-stay psychiatric beds, every consultant psychiatrist in Glasgow was asked to consider whether long-stay patients in his or her wards would be fit for rehabilitation and return to the community. For the purposes of the survey, long stay was defined as a single admission of at least six months, but patients with an organic diagnosis who were aged over 65 were excluded. It was estimated that, with rehabilitation, almost a third of the patients surveyed could return to the community, and that, with more participation in self-care, over 15% might be able to manage in a ward or hostel within the the hospital. Patients judged fit to return to the community were preponderantly younger patients with a shorter period of in-patient care, and those suffering from a functional psychotic illness. PMID- 2597854 TI - Community management of schizophrenia. A two-year follow-up of a behavioural intervention with families. AB - The relapse and readmission rates of schizophrenic patients who participated in a controlled trial of a nine-month behavioural family intervention trial based on the EE status of their relatives are presented at two years. The patients who received the behavioural family intervention had lower rates of relapse and readmission than patients from high-EE homes who had received a short educational programme or routine treatment. The relapse rate of the behavioural family intervention group (33%) was the same as that of the low-EE group (33%), and significantly lower than that of the non-intervention high-EE group (59%). PMID- 2597856 TI - A study of factors associated with response to electroconvulsive therapy in patients with schizophrenic symptoms. AB - Seventeen patients with schizophrenic symptoms were assessed before and after ECT to elicit possible factors predictive of outcome. The strongest associations with good outcome were shown by short duration of illness and paucity of pre-morbid schizoid personality traits; significant associations were also shown by short duration of current episode, paucity of paranoid pre-morbid personality traits, and the presence of perplexity. The diagnosis of schizoaffective disorder was not related to outcome. Questionnaires completed by 16 patients after ECT showed their attitudes to be generally favourable to the procedure. PMID- 2597855 TI - Family history and cerebral ventricular enlargement in schizophrenia. A case control study. AB - Ventricular size was measured from CT scans in 48 patients meeting RDC for schizophrenia who had a first-degree relative with a history of treatment for major psychiatric disorder, in 48 age- and sex-matched schizophrenic patients with no such history in first- or second-degree relatives, and in 48 matched, healthy controls. There was no difference in ventricular size between those with and without a positive family history, although both groups showed ventricular enlargement with respect to normal controls. Ventricular enlargement was demonstrated in the subgroup of 23 patients with a family history of schizophrenia, but not in the subgroup of 18 patients with a family history of affective disorder. These observations provide further evidence that schizophrenics with a family history of affective disorder may constitute an aetiologically distinct subgroup. PMID- 2597857 TI - A family study of two subgroups of schizoaffective patients. AB - A family study was carried out in two groups of patients fulfilling RDC for schizoaffective disorder: in one, a full affective and a full schizophrenic syndrome were simultaneously present; in the other, affective and schizophrenic features appeared within a polymorphic and rapidly changing clinical picture, with depersonalization/derealization and/or confusion. In the first-degree relatives of patients of the former group, the risk of major psychiatric disorders was not significantly different from that of relatives of schizophrenics, whereas in the first-degree relatives of patients of the latter group a low risk for both schizophrenia and major affective disorders, and a relatively high risk for schizoaffective disorders, were observed. PMID- 2597858 TI - The relationship between depression and hopelessness. Implications for current theories of depression. AB - In both Beck's cognitive theory of depression and Brown & Harris's sociopsychological model, hopelessness is given unwarranted universality and centrality. Empirical evidence contradicting this element of the two theories has been ignored, and two new investigations are presented which suggest the existence of 'non-hopeless' depression. A more complete account of the heterogeneous nature of depression is now required. PMID- 2597859 TI - The hormonal environment of post-natal depression. AB - The incidence of post-natal depression is high, and dramatic changes in steroid hormones and prolactin occur in the post-partum period. In an attempt to correlate these events, 147 mothers, six to eight weeks after delivery of a healthy infant, completed standard psychological tests, including the Edinburgh, Montgomery-Asberg, and Raskin scales. They also provided matched samples of plasma for assay of cortisol, oestradiol, progesterone and prolactin, and saliva for assay of cortisol and progesterone. All steroid concentrations were within the appropriate normal ranges. Of the mothers, 14.9% were depressed on all three scales. Significant correlations were seen between depression ratings and salivary progesterone and prolactin. In bottle-feeders, salivary progesterone was positively associated with depression, whereas in breast-feeders it was negatively associated. Plasma prolactin levels were inappropriately low in depressed breast-feeders. These data indicate that differing therapies may be appropriate for depression in breast- and bottle-feeders. PMID- 2597860 TI - Depression following spinal cord injury. A prospective in-patient study. AB - In a systematic prospective study of 71 patients with acute spinal cord injury carried out in the acute and rehabilitation phases of treatment, 14 patients meeting the DSM-III criteria for major depressive disorder were identified. A further 13 patients had transient periods of depressed mood, while the majority of patients showed no clear evidence of depression. The BDI was found to be valid in this group of patients. PMID- 2597861 TI - Quality of parenting in alcoholics and narcotic addicts. AB - Alcoholics and heroin addicts were compared with a normal control group to determine whether there were differences in quality of parenting during childhood, assessed using the Parental Bonding Instrument. Maternal and paternal overprotection were reported more commonly by narcotic addicts. Maternal overprotection alone was implicated in alcoholics. Narcotic addicts seem to have more disturbed parenting than alcoholics, especially paternal parenting. PMID- 2597862 TI - Anorexia nervosa in Hong Kong. Why not more in Chinese? AB - Anorexia nervosa is a geographically distinct psychiatric disorder; it is rapidly increasing in incidence in Western countries, while being virtually unreported in China, or in the Chinese community of Hong Kong. This is surprising when the Chinese preoccupation with food and their reported readiness to somatise dysphoria are considered. Three Chinese anorectics born and living in Hong Kong and exhibiting mostly typical clinical features are reported. The rarity of the disorder in the East could be related to protective biological and socio-cultural factors specific to the Chinese, and while it may become more common, anorexia nervosa is unlikely to reach Western proportions. PMID- 2597863 TI - 'Asneezia'--some further observations. AB - Absence of sneezing or inability to sneeze was found in 2.6% of psychiatric patients, although only half complained of the symptom spontaneously. This was the most frequent of a triad of features, the others being infrequent attacks, of coryza and light-headedness. Endogenous depression was the commonest psychiatric diagnosis, followed by schizophrenia, but 'asneezics' differed significantly from controls in their diagnostic distribution; they also tended to be older, poorer, and less educated. The course and outcome of the asneezic triad ran almost parallel to those of the primary psychiatric illness. PMID- 2597864 TI - The occurrence of depression following mania. A method of predicting vulnerable cases. AB - In a retrospective analysis of 100 cases of mania (1981-1985), the incidence of subsequent depression was found to be 30%. Its occurrence was significantly associated with three factors: cyclothymic pre-morbid personality, family history of affective disorder, and past history of depression. By discriminant analysis, outcome could be predicted successfully in 81% of cases. PMID- 2597865 TI - Alexithymia, masked depression and loss in a Holocaust survivor. AB - A woman who suffered multiple losses in childhood and adolescence became depressed 40 years later, after a series of new losses. Concomitant alexithymic features caused a masking of her depression by somatic symptoms. The relationships between alexithymia, masked depression and loss are discussed. PMID- 2597866 TI - Cholinergic syndrome following anticholinergic withdrawal in a schizophrenic patient abusing marijuana. AB - A 27-year-old neuroleptic-stabilised schizophrenic patient presented with a three day history of psychomotor retardation, disturbed sleep, and social and emotional withdrawal following reduction of his anticholinergic dosage; his symptoms had intensified after an increase in neuroleptic dosage, based on a diagnosis of psychotic decompensation. Recognition of a cholinergic syndrome and institution of appropriate anticholinergic treatment resulted in rapid improvement. The clinical distinction between a cholinergic overdrive state and schizophrenic exacerbation, while sometimes difficult, can be critical in selecting appropriate management. PMID- 2597867 TI - De Clerambault's syndrome (erotomania) in organic delusional syndrome. AB - A patient with de Clerambault's syndrome (erotomania) following brain damage and epilepsy is described. The delusion appeared after brain surgery for subarachnoid haemorrhage, and remained chronic. Erotomania in this patient may be judged to be aetiologically related to organic brain damage. PMID- 2597868 TI - Repetition of parasuicide. PMID- 2597869 TI - Loss and theft. PMID- 2597870 TI - The use of propofol for anaesthesia during ECT. PMID- 2597871 TI - Sex chromosomes and psychosis. PMID- 2597872 TI - Elderly eccentrics. PMID- 2597873 TI - Is globus hystericus? PMID- 2597874 TI - Hospital suicides. PMID- 2597875 TI - Homo-erotomania. PMID- 2597876 TI - Violence in sleep: a further diagnostic consideration. PMID- 2597877 TI - Chronic patients in acute wards. PMID- 2597878 TI - Nosological problems. PMID- 2597879 TI - Admission trends. PMID- 2597880 TI - The mind-body problem. PMID- 2597881 TI - Psychological-mindedness and the alexithymia construct. PMID- 2597882 TI - Illicit drug use in strength athletes. PMID- 2597883 TI - Counselling the relatives of the long-term adult mentally ill. II. A low-cost supportive model. AB - A psychosocial intervention is described geared to the needs of carers of the long-term mentally ill, which is feasible for a busy clinical team to implement: relatives were not selected for the group by patient diagnosis or motivation and little extra staff input was required. An interactive education session at home was followed by a monthly relatives group which aimed to reduce components of expressed emotion (EE) and to alleviate burden. The group facilitators adopted a directive but non-judgemental style, and constructive coping efforts were encouraged. The intervention was effective at reducing EE and improving family relationships. The study offers a realistic model of how to offer support to people providing long-term care for the severely mentally ill. PMID- 2597884 TI - The natural history of mental disorder in old age. A long-term study. AB - In a prospective study, 153 consecutive new referrals to a psychogeriatrician in Oxfordshire in 1973 were followed up for 15 years. The percentage of the over-65 population at risk was 0.27 and, of those aged over 80, 0.6. Alzheimer's dementia and depressive illness comprised over two-thirds of referrals. A quarter became permanent admissions, half of them with Alzheimer's dementia, 19% of whom were alive five years later. Depressive illness, at ten years, had a mortality 1.2-1.6 times that of the population at risk. The distinction between Alzheimer's dementia and depressive illness, based on their natural history and causes of death, was reinforced. PMID- 2597885 TI - The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. AB - Nicotine in patients with dementia of the Alzheimer type (DAT) produced a significant and marked improvement in discriminative sensitivity and reaction times on a computerised test of attention and information processing. Nicotine also improved the ability of DAT patients to detect a flickering light in a critical flicker fusion test. These results suggest that nicotine may be acting on cortical mechanisms involved in visual perception and attention, and support the hypothesis that acetylcholine transmission modulates vigilance and discrimination. Nicotine may therefore be of some value in treating deficits in attention and information processing in DAT patients. PMID- 2597886 TI - Eating habits in dementia. A descriptive study. AB - The eating habits of 33 patients with dementia were studied. They were assessed by semistructured interview with a relative who was able to act as an informant for the whole period of the dementia. Changes in eating were found to be common and included both increased and decreased food intake, altered food choice, the consumption of inedible substances and disturbances in the process of eating. The clinical significance of these changes and some likely underlying mechanisms are discussed. PMID- 2597887 TI - The validity of the eating disorder examination and its subscales. AB - The EDE is a semistructured interview which has been developed as a measure of the specific psychopathology of anorexia nervosa and bulimia nervosa. To establish its discriminant validity it was administered to 100 patients with anorexia nervosa or bulimia nervosa and to 42 controls. The two groups differed significantly on all items. Five subscales were derived on rational grounds and evaluated on the two populations. The alpha coefficients for each subscale indicated a satisfactory degree of internal consistency. The EDE provides clinicians and research workers with a detailed and comprehensive profile of the psychopathological features of patients with eating disorders. PMID- 2597888 TI - The use of rating scales to identify post-natal depression. AB - One hundred and forty-seven mothers were screened for major depression at six to eight weeks post-partum. Using predetermined cut-off points, the Edinburgh Postnatal Depression Scale and the Beck scale were compared in their abilities to identify the 15% of subjects who had major depression according to DSM-III criteria. The sensitivity of Edinburgh scale was 95% and its specificity 93%. The performance of the Beck scale was markedly inferior, with a sensitivity of 68% and specificity of 88%. PMID- 2597889 TI - Maternal depression and the emotional development of the child. AB - Ninety-two women and their first-born children took part in a longitudinal survey of maternal mental health. When the children were four years old, their mothers were interviewed by means of the Behavioural Screening Questionnaire, and the children's problems were rated by a psychiatrist, who was unaware of the mothers' psychiatric histories or of assessments of their current health. As expected, mothers who were concurrently depressed reported significantly more behavioural difficulties in their children. Marital disharmony during pregnancy and a history of paternal psychiatric problems were also associated with later childhood behavioural difficulties. Children who scored below average on the McCarthy scales of cognitive abilities were also reported by their mothers to have more behavioural problems, but the children's behavioural difficulties at four showed no clear links with post-natal depression. PMID- 2597890 TI - The effects of childhood parental death and divorce on six-month history of anxiety disorders. AB - Duke Epidemiologic Catchment Area (ECA) data were used to examine the relationships between: (a) early childhood maternal death, paternal death, and parental separation/divorce, and (b) six-month DIS/DSM-III diagnoses of agoraphobia with and without panic attacks, simple phobia, social phobia, panic disorder, generalised anxiety disorder, and obsessive-compulsive disorder. Associations were found between: (a) maternal death and agoraphobia with panic attacks, and (b) parental separation/divorce and agoraphobia with panic attacks and panic disorder. The associations could not be explained by the effects of potentially confounding socio-demographic factors. PMID- 2597891 TI - A follow-up of adolescents with obsessive-compulsive disorder. AB - Twenty-six patients seen at a regional adolescent psychiatry unit between 1974 and 1979 with a discharge diagnosis of obsessive-compulsive disorder were followed up after an average of ten years. Of 24 subjects traced, outcome information was obtained from 20. At the point of follow-up, ten patients remained psychiatrically ill, six having persisting obsessive-compulsive symptoms. Poor outcome was associated with a family history of psychiatric illness and lack of response to therapy at initial contact. All patients who were asymptomatic at discharge had remained well. PMID- 2597892 TI - Types of opiate addiction and notification to the home office. AB - Hospitalised drug addicts were categorised according to the time lapse between onset of their opiate abuse and their first notification to the Home Office. Late notification correlated with a lower level of dependence, a more intermittent pattern of misuse, and a greater likelihood of alcohol abuse. It is postulated that there may be two types of addiction which lie along a continuum. PMID- 2597893 TI - Would monitoring by electroencephalogram improve the practice of electroconvulsive therapy? AB - Estimates of seizure length made by the treating psychiatrist were compared with estimates made by six-channel EEG in 100 electroconvulsive treatments in 22 depressed patients. In 70 treatments the doctor observed a fit which was shorter than 25 seconds. No doctor restimulated a patient in such a case and on only three occasions was the electrical stimulus increased at the next treatment. EEG monitoring revealed that only 30 of the treatments resulted in a seizure of less than 25 seconds, and this was detected in almost all cases by the treating doctor. The potential value of EEG monitoring was to identify patients whose visible seizure was short but where cerebral seizure length was satisfactory. Trainee psychiatrists often mismanage patients who have short seizures. PMID- 2597894 TI - Tricyclic wash-out and growth hormone response to clonidine. AB - We have observed a significantly higher growth hormone (GH) response to clonidine administration (150 micrograms i.v.) in 14 patients with a major depressive disorder who had never received antidepressant therapy than in 14 matched depressive patients who had not received tricyclic drugs for at least 15 days. Compared with a control group of eight subjects, untreated depressed patients, as a group, had a normal response, while matched patients had markedly blunted response. Results for the group of untreated depressed patients showed that some patients had a blunted response while others had a response in the normal range. The results suggest that studies on the GH response to clonidine in psychiatric patients need to take into account the confounding and long-lasting effects of tricyclics. PMID- 2597895 TI - Psychiatric justice. PMID- 2597896 TI - Szasz on psychiatric justice. PMID- 2597897 TI - Multiple personality disorder. PMID- 2597898 TI - Which patients will respond to ECT? PMID- 2597900 TI - Depression in attempted suicide. PMID- 2597899 TI - EEG monitoring of ECT. PMID- 2597901 TI - Molecular genetics and ethics. PMID- 2597902 TI - Lipid-lowering drugs and violence. PMID- 2597903 TI - Paradoxical intervention. PMID- 2597904 TI - What's so special about two years anyway? PMID- 2597905 TI - CPK levels and neuroleptic malignant syndrome. PMID- 2597906 TI - Post-traumatic stress. PMID- 2597908 TI - The opiate prescribing debate. PMID- 2597907 TI - Listeria and psychiatric syndromes. PMID- 2597909 TI - Children surviving parental murder. PMID- 2597910 TI - Capgras' syndrome and town duplication. PMID- 2597911 TI - French empirical criteria for the diagnosis of non-affective non-organic psychoses. Comparison between the criteria suggested by Professors Pull and Pichot and those of DSM-III-R. AB - At the end of the 19th century, when the current psychiatric diagnostic concepts used in most countries were being elaborated, in Germany particularly by Kraepelin, French-speaking psychiatrists, who until then had dominated European psychiatry, continued to develop their own system. This difference in classification is most apparent in the non-organic, non-affective psychoses. Although some of the French names used may be unfamiliar to anglophones, when the new 'consensus' criteria developed by Professors Pull and Pichot are compared with the DSM-III-R criteria it becomes apparent that the French and American concepts are converging. PMID- 2597912 TI - Slowly progressive schizophrenia--myth or clinical reality? PMID- 2597913 TI - Chronic psychiatric complaints and the General Health Questionnaire. AB - The sensitivity of the GHQ and a revised scoring procedure (CGHQ) for chronic psychiatric complaints was investigated on 175 out-patients. The mean level of severity of symptoms of the groups with and without chronic complaints was not significantly different. However, patients with chronic complaints showed a significantly lower mean GHQ score than patients without chronic complaints. The mean CGHQ scores of the two groups did not differ, suggesting that the CGHQ is a better indicator of the severity of the chronic psychiatric state than the GHQ. The revised scoring procedure resulted in a decrease in the number of false negatives. The strongest reduction in false negatives, however, was induced by a combination of the original and the revised scoring procedures. This reduction was achieved at the expense of only a small increase in the number of false positives. Altogether, the revised scoring procedure proved to be only marginally better. PMID- 2597914 TI - Differential classification in school refusal. AB - It has been argued that school refusal may not be a unitary syndrome, but a common presenting symptom founded on differing underlying dynamics. The paper explores this hypothesis empirically. The clinical files of 100 refusers were scored for several variables which could potentially differentiate between school refusal subtypes, and for several commonly accepted beliefs about school refusal. The data were subjected to a variety of analyses, culminating in cluster analysis. Cluster (C) 1 consisted of children who feared separation from dependent, overprotective mothers. C2 youngsters were perfectionistic and depressed. They dominated mothers who had been deprived in childhood. C3 consisted of extensively disturbed children from multiproblem families, who had suffered early separation or loss, and who were fearful and depressed. PMID- 2597915 TI - Distorting patient or distorting instrument? Body shape disturbance in patients with anorexia nervosa and bulimia. AB - Three current techniques for estimating body size (Image Marking, Visual Size Estimation, and Distorting Video techniques) were compared. Anorexia nervosa and bulimic patients and normal control subjects were required to make size judgments of the way they 'knew' they looked, the way they 'felt' they looked, and of the width of an inanimate control object. Results from the three techniques were not the same, thus implying that research findings can no longer be cross-compared. Moreover, while all subjects were similar in the accuracy of their estimation of a control object, anorexia nervosa and bulimic patients overestimated their own body size significantly more than normal controls. This difference was even more marked when affective instructions were compared. PMID- 2597916 TI - Wilson's disease: a prospective study of psychopathology in 31 cases. AB - A prospective neuropsychiatric study of 31 consecutive subjects with Wilson's disease is reported. Exploratory factor analysis yielded four factors: neurological, cognitive, hepatic/depressive and psychiatric. Significant associations were found between a 'psychopathic' personality factor and neurological and dysarthria scores. The d' and beta coefficients of a signal detection memory task dissociated: the former correlated only with Mini-Mental State and Benton visuospatial task; and the latter with depressive symptoms. Using discriminant function analysis, there was efficient classification of 'psychopathic' personality by dysarthria, and of individual depressive symptoms by disturbance of gait. Biochemical markers of hepatic dysfunction were significantly associated with certain depressive symptoms. No evidence emerged to support the putative association with schizophrenia-like psychosis. PMID- 2597917 TI - An epidemiological study of dementia in a rural population of elderly women. AB - A study of 365 women aged 70-79 in a rural community was carried out using the Cambridge Examination of Mental Disorders in the Elderly (CAMDEX). Prevalence rates of dementia are reported by severity for the 70-74 and 75-79 age groups. Differential diagnosis was made according to CAMDEX guidelines. Senile dementia of Alzheimer type accounted for half the dementia cases. The prevalence rates overall did not differ from those reported in other recent studies, but the rates for levels greater than mild/moderate were lower, despite the inclusion of subjects in institutions. PMID- 2597919 TI - Schizophrenia and the perception of emotions. How accurately do schizophrenics judge the emotional states of others? AB - Audiovisual tapes of emotional situations were shown to 34 schizophrenics and 15 controls who were asked to rate the emotional content of the scenes using an adjective check-list. The schizophrenic patients failed to detect the dominant character of the scenes, and perceived the opposite emotions to those perceived by the controls. Such deviant responses were not related to paranoid symptoms, flattened affect, formal thought disorder, general level of morbidity, or duration of in-patient stay. PMID- 2597918 TI - Mania in the elderly. AB - A retrospective study of 92 patients admitted with mania, aged over 65 years of age, found that 26% had no prior history of affective illness; 30% had previously only experienced depression, and half of these had at least three episodes of depression before the first manic illness. Patients with a family history of affective disorders had a significantly earlier age of onset of illness. There was evidence of cerebral organic impairment in 24% of the patients, and this group had a significantly later age of onset of illness. Prognosis was good, with only 8% still in hospital at six months. Half of the patients were started on lithium prophylaxis, but this did not significantly alter the number of readmissions. A quarter of those started on lithium developed evidence of lithium toxicity. PMID- 2597920 TI - The contributions of problem drinking to the level of psychiatric morbidity in the general hospital. AB - Of 331 patients admitted to a general hospital to whom the CAGE questionnaire was administered, those who scored 2 or more for alcoholism scored higher on a number of measures of psychiatric morbidity than those with a CAGE score of 0. Those patients who scored 1 showed less psychiatric morbidity than those who scored 0. Among the male patients who scored at least one question positively, those who had abstained from alcohol for at least a year showed higher levels of psychiatric morbidity than those still drinking. PMID- 2597921 TI - Resettlement of old long-stay psychiatric patients: the use of the private sector. AB - A follow-up study of 17 old long-stay psychiatric patients resettled in private facilities for the elderly is reported. Resident satisfaction with the placement and functioning (using the CAPE Behaviour Rating Scale) was assessed, together with the quality of the physical and social environment, and the regime characteristics in the establishments. All residents were satisfied with life and their functioning had improved significantly. The private facilities were more resident-orientated, and had a generally superior social environment to their local authority 'old people's home' counterparts. The physical amenities, safety features, and architectural choice available were of a similar standard to those in local authority old people's homes, but there were fewer prosthetic and orientational aids and on-site recreational amenities. PMID- 2597923 TI - Pimozide in pathological jealousy. AB - A 39-year-old man had his pathological jealousy successfully treated with pimozide. It is suggested that pimozide might be considered the drug of choice in all the monodelusional disorders. PMID- 2597922 TI - Epilepsy and violence. AB - Epileptic automatism and violence are seldom found among temporal lobe epileptics. The case of a 19-year-old girl who killed a 20-month-old child during an epileptic attack is described, and the literature and medico-legal issues are briefly reviewed. PMID- 2597924 TI - A Chinese classic phenylketonuria manifested as autism. AB - A 12-year-old Chinese boy had a diagnosis of infantile autism at infancy that was finally confirmed as classic phenylketonuria at adolescence. This treatable inborn metabolic disease should be investigated in cases of apparent autism, especially where mass neonatal screening of inborn metabolic diseases has not been established. PMID- 2597925 TI - 'Puerperal psychosis' following male-to-female sex reassignment? AB - Psychosis is reported following abrupt withdrawal of oestrogen and surgery for male-to-female sex reassignment. The resemblance of the patient's mental state to puerperal psychosis suggested a hormonal aetiology. PMID- 2597926 TI - Syphilis serology screening in a psychogeriatric population. Is the effort worthwhile? AB - The treponemal serological status of 800 patients above the age of 65 was reviewed. Twenty-one were found to be positive and the venereologists advised against treatment in all referred cases. The question is posed whether syphilis serology screening in the elderly mentally ill should be confined to those patients with obvious clinical manifestation of syphilis or with obscure psychiatric presentations. PMID- 2597927 TI - Use of seclusion in Scotland. PMID- 2597928 TI - Attitudes to seclusion in Virginia. PMID- 2597929 TI - Australian depression. PMID- 2597930 TI - Obstetric liaison. PMID- 2597931 TI - Practical administration of ECT. PMID- 2597932 TI - Risk factors in schizophrenia. PMID- 2597933 TI - Attitudes to anxiety. PMID- 2597934 TI - The epileptic arsonist. PMID- 2597935 TI - Close encounters of the witness kind: children's memory for a simulated health inspection. AB - A total of 128 children from each of two age groups (6-7 years and 10-11 years) took part individually in a simulated health check procedure. This involved direct confrontation between the child and an adult stranger in which the child was touched and an article of clothing (shoes) removed. One week later children took part in a series of tests which examined their testimony of the events in which they participated. Older children were superior to younger on both free and prompted recall of event and appearance information and made fewer errors, both relatively and absolutely, on recall of appearance but not events. The two age groups did not differ in their competence in the construction of Photofit pictures and showed no difference in performance on identification from a photographic array, irrespective of whether the adult was present or absent. The implications of these findings for the current debate over the legal admissibility of children's evidence are discussed. PMID- 2597936 TI - Genetic and environmental mechanisms determining intelligence, neuroticism, extraversion and psychoticism: an analysis of Irish siblings. AB - The theory that shared family environment has an effect on intelligence but no effect on personality was examined by a study of correlations between young adolescent Irish siblings for intelligence, neuroticism, extraversion and psychoticism. The correlations obtained for 386 sibling pairs were 0.48 (intelligence), 0.06 (neuroticism), 0.31 (extraversion) and 0.14 (psychoticism). The correlation for IQ confirms the operation of both genetic and shared family effects on intelligence. The low correlations for neuroticism and psychoticism confirm the thesis that shared family effects have no influence on these traits. They are also inconsistent with an additive genetic model and suggest that non additive genetic mechanisms are present to make siblings so dissimilar. The higher sibling correlation for extraversion suggests that shared family environment does have some effect on this trait among young adolescents and is also consistent with an additive genetic model. PMID- 2597937 TI - Human reactions to reward and punishment: a questionnaire examination of Gray's personality theory. AB - The development of the Gray-Wilson Personality Questionnaire is described; this is an instrument designed to measure human equivalents of six animal behaviour paradigms--Approach, Active Avoidance, Passive Avoidance, Extinction, Fight and Flight. Although these six scales showed satisfactory internal consistency they failed to link up into the three major systems suggested by Gray's personality theory. The strongest associations were between Fight and Approach and between Flight and Passive Avoidance. This raises questions as to how the neurological systems of activation, inhibition and fight/flight are related to human personality structure. PMID- 2597938 TI - Tactile perceptual asymmetry: the influence of motor activity and imagery instructions. AB - The purpose of this study was to examine the degree to which changes in muscular activity modify tactile perceptual asymmetries. In two experiments subjects were presented with a series of pairs of random shapes to the fingers of each hand. Their task was to detect the occurrence of a previously learnt target shape. Pressing on to the shape was the only movement allowed and other types of motor activity, particularly tracing movements, were not permitted. Across experimental conditions subjects were required to change the pressure and hence muscular effort used to press upon the shape. A left-hand advantage was found across all experimental conditions and its size did not change when subjects were required to press either firmly or lightly upon the shapes. This result was also found when subjects were required to apply uneven pressure between the hands. One-half of the subjects also performed the experimental conditions following instructions to use imagery. This produced an enhancement of right-hand performance on the task with a loss of the left-hand advantage. The results suggest that observed tactile perceptual asymmetries, while unaffected by changes in muscular effort, are easily overridden by higher-order cognitive and motor processes. PMID- 2597939 TI - Skin cancer in renal transplant recipients. AB - Skin cancer was found in 31 of 598 patients transplanted in Oxford. No cases occurred during the first 3 years after transplantation but the prevalence rose after 12 years to 18.2 per cent. The main risk factors predisposing to skin cancer were the time after transplantation and male sex. Comparison with data from other centres suggests that exposure to ultraviolet light is a major aetiological factor in the speed of development of skin cancer. As the incidence of new cases rose progressively with time in our patients, it would seem that skin cancer is likely to become a major clinical problem as more patients enjoy prolonged survival after renal transplantation. Preventative and screening measures should be taken by transplant units both in the UK and in other countries with similar temperate climates. PMID- 2597940 TI - Analysis of 828 servicemen killed or injured by explosion in Northern Ireland 1970-84: the Hostile Action Casualty System. AB - Death and injury due to terrorist bombings continue to exercise civilian and military surgeons alike. In this paper 828 servicemen killed and injured by explosions in Northern Ireland have been studied, using data stored in the Hostile Action Casualty System (HACS). Because of the nature of the conflict in Northern Ireland, the magnitude of each explosion and the distance of the victims from it are quite accurately known. The overpressure (blast loading) to which the victim was exposed can be estimated from the information on the HACS forms and standard tables, giving overpressures for a given change at a known distance. Using the HACS data, the numbers of injuries due to overpressure (primary blast injury), missiles energized by the blast (secondary injury), displacement of the victim by the blast wind (tertiary injury) and flash burn can be determined. Of the 828 servicemen involved in explosions, 216 were killed, most of them before any treatment could be instituted. Of the servicemen in the survey, 90 per cent were wearing body armour. Although body armour affords considerable protection from secondary missiles, it is unlikely to reduce the number of deaths due to primary blast injury. PMID- 2597941 TI - Anastomotic aneurysms of the femoral artery: aetiology and treatment. AB - The aetiology and treatment of 35 femoral false anastomotic aneurysms in 29 patients presenting over the 4-year period 1984-88 were reviewed retrospectively. The mean interval between primary anastomosis and false aneurysm repair was 6 years (range from 2 weeks to 16 years). Twenty-two (63 per cent) false aneurysms had occurred after previous aortobifemoral bypass grafting for occlusive aortoiliac disease. Seven (20 per cent) presented as acute surgical emergencies. Review of the records of the initial operations revealed that superficial wound infections with positive bacteriological cultures had been present in eight cases (23 per cent) and a further two (6 per cent) had lymph fistulae. Thirty-two false aneurysms were repaired, by simple reanastomosis in 14 cases, interposition grafting in 17 cases and in one case by complete revision to an aortobifemoral bypass graft. The risk of a further operative repair was less (P less than 0.05) following interposition grafting, than after simple revision. False aneurysm repairs, when compared with primary reconstructions done during the same period, were associated with more superficial wound infections (37 versus 10 per cent) and more explorations for haemorrhage within 30 days (19 versus 7 per cent). PMID- 2597942 TI - Abdominal aortic aneurysm repair in the over eighties. AB - Between January 1980 and September 1988, 34 octogenarians underwent aortic aneurysm repair. There were 26 men and eight women with a median age of 83 years (range 80-88 years). Twenty underwent 'emergency' repair after presenting with pain and/or collapse: 11 with a retroperitoneal rupture, three with an intraperitoneal rupture and six with an expanding aneurysm. The mortality rate for this group was 35 per cent. During the same period 14 patients had an elective repair and there were no deaths within 30 days. The mean hospital stay for the elective group was 14.2 days compared with 17.0 days for survivors in the emergency group. There was no significant difference in terms of risk factors between those who developed postoperative complications and those who did not. These mortality rates compare favourably with our overall mortality results for elective (4.6 per cent) and emergency (31 per cent) surgery. Those patients over 80 years of age with infrarenal abdominal aortic aneurysms should not be refused surgery on the basis of age alone; each patient should be judged individually. PMID- 2597943 TI - Acute lower limb arterial ischaemia: a role for continuous oxygen inhalation. AB - Simultaneous readings of transcutaneous partial pressure of oxygen (Ptc,O2) were obtained from the left anterior chest wall, from 10 cm distal to the medial aspect of the knee joint, and from the first dorsal webspace in 16 patients with acute peripheral arterial ischaemia of the leg. Oxygen was administered at concentrations of 24, 40, 60 and 100 per cent. Mean (s.d.) initial chest Ptc,O2 (53(17)mmHg) was significantly higher than that of the medial lower limb site (37(17)mmHg). After inhalation of 24 per cent oxygen, a statistically significant (P less than 0.025) increase in chest Ptc,O2 was achieved (63(20)mmHg), but the increase in Ptc,O2 (43(19)mmHg) at the medial lower limb site was not statistically significant. Inhalation of 40 per cent oxygen resulted in significant increases at both sites (chest: 83(23)mmHg, P less than 0.01; limb: 53(26)mmHg, P less than 0.05). Ptc,O2 in the limb at this concentration of inhaled oxygen was equal to the initial chest level. Increasing the oxygen concentration to 60 per cent and then to 100 per cent produced further significant (P less than 0.001) increases in Ptc,O2 at both sites. The use of continuous oxygen inhalation during acute ischaemia may improve tissue nutrition before, during and after definitive treatment. PMID- 2597944 TI - Electrocardiographic guided placement of central venous catheters. PMID- 2597945 TI - Complications of parotid surgery: the need for selectivity. AB - The morbidity rate following 112 operations on the parotid gland is reported. Facial nerve palsy (temporary, 38 per cent; permanent, 9 per cent) and Frey's syndrome (11 per cent) were common following superficial parotidectomy. For pleomorphic adenoma and malignant lesions this procedure is justified. Benign conditions, which can be diagnosed preoperatively, should be treated by more limited surgery which has a lower complication rate. PMID- 2597946 TI - Resectability of large focal liver lesions. AB - Despite modern imaging techniques evaluation of the resectability of large focal liver lesions is often difficult or impossible until the time of operation. Based on experience with 54 primary or secondary focal liver tumours, a simple morphological classification has been found to be reasonably predictive of resectability. All tumours were classified before operation using computed tomography, ultrasound and angiography; 38 patients underwent laparotomy. Dependent, 'hanging' tumours (n = 7) were resected in six cases, expansively growing 'pushing' tumours (n = 19) were resected in 18 cases, and infiltrating, 'invasive' tumours (n = 17) were not resected because of involvement with major vascular structures. Eleven small tumours (less than 5 cm) were not classifiable by this system. This simple classification may be a useful clinical concept in preoperative assessment of resectability of focal liver lesions. Hanging tumours should always be resected, and large expansile tumours are generally resectable despite their size. Invasive tumours can only be resected in exceptional cases. PMID- 2597947 TI - Alkaline battery-induced tracheo-oesophageal fistula. PMID- 2597948 TI - Bile leaks after simple cholecystectomy. AB - Drains after cholecystectomy are used commonly to avoid biliary leaks and subsequent peritonitis. Thirty-five patients who had had cholecystectomy without drainage underwent 99mTc-labelled dimethylphenylcarbamoylmethyliminodiacetic acid (HIDA) and ultrasound scans the morning after surgery. Biliary leaks detected by positive HIDA scans occurred in 11 patients. Subhepatic fluid collections were seen on 20 ultrasound scans. There was no relation between biliary leaks and subhepatic collections. Many of the collections were not seen on the HIDA scan, suggesting that they contained blood and not bile. Many of the patients with bile leaks showed no fluid collection. Clinical complications were few and evenly distributed between those with positive and negative scans. We conclude that bile leaks are not an occasional event but occur after 31 per cent of undrained cholecystectomies and that these bile leaks remain clinically unimportant. PMID- 2597949 TI - Critical assessment of the quality of continence after postanal repair for faecal incontinence. AB - One hundred and twenty-four patients had a postanal repair for the treatment of faecal incontinence between January 1976 and July 1987. One hundred and sixteen of these patients have been followed up for more than 1 year with a median follow up of 5 years. Incontinence was improved in 81 per cent of patients. Furthermore, bowel frequency fell: 58 per cent had more than four bowel movements before operation compared with 19 per cent after operation. However, 60 per cent of patients still claimed urgency, 76 per cent still leaked faeces and 52 per cent continued to wear pads after the operation. Maximum resting anal pressure and maximum squeeze pressure did not change significantly after operation either in patients whose bowel control was improved or in those who were not. The results indicate that the quality of continence after postanal repair is poor. PMID- 2597950 TI - Anterior sphincter plication and levatorplasty in the treatment of faecal incontinence. AB - The surgical treatment of faecal incontinence has been traditionally divided into sphincteroplasty for sphincter disruption and postanal repair for idiopathic cases. However, many studies have failed to show a correlation between outcome and change in the anorectal angle. This study was carried out to determine the effectiveness of anterior sphincteroplasty and levatorplasty in the treatment of faecal incontinence, regardless of aetiology. Thirty consecutive patients underwent surgery, 14 with traumatic sphincter injuries and 16 with idiopathic faecal incontinence. A satisfactory clinical result was obtained in ten (71 per cent) patients in the traumatic group and in ten (62 per cent) in the idiopathic group. This was associated with a significant increase in maximum voluntary contraction pressure in the traumatic group and in those patients who had a good result in the idiopathic group (traumatic: preoperative median 80 cmH2O (range 50 115 cmH2O) versus postoperative 115 cmH2O (75-290 cmH2O), P less than 0.005; idiopathic: preoperative 105 cmH2O (45-190 cmH2O) versus postoperative 120 cmH2O (45-230 cmH2O), P less than 0.05; Wilcoxon paired signed ranks test). There was also significant improvement in anal sensation in the upper anal canal in both groups (traumatic: preoperative mean 17 mA versus postoperative 11 mA, P less than 0.05; idiopathic: preoperative 24 mA versus postoperative 9 mA, P less than 0.02). The anorectal angle increased in the idiopathic group at rest (preoperative median 105 degrees (range 86-152 degrees) versus postoperative 118 degrees (95-180 degrees), P less than 0.05). In conclusion, the type of approach (anterior or posterior) and the anorectal angle are irrelevant to the outcome of surgery for idiopathic faecal incontinence. Success appears to be related more to improved sphincter pressure and anal sensation. PMID- 2597951 TI - Declining indications for abdominoperineal resection. AB - In 126 consecutive patients operated on for carcinoma of the lower two-thirds of the rectum, a consistent policy of sphincter preservation resulted in 100 (79 per cent) having anterior resection and 22 (17 per cent) abdominoperineal resection. Perioperative complications in the anterior resection group were: death (two patients), clinical leakage (three patients), pulmonary embolism (five patients), pelvic haematoma (one patient), small bowel obstruction (one patient) and wound sepsis (six patients). Of 55 patients who had a potentially curative anterior resection with follow-up of at least 2 years, one developed local recurrence. Five per cent of patients had significant continence problems. Low anterior resection for carcinoma is associated with low perioperative morbidity, satisfactory functional results and acceptable local recurrence rates. PMID- 2597952 TI - Non-condylomatous, perianal disease in homosexual men. AB - This retrospective study details the findings and outcome in 34 homosexual men, out of a total of 177 patients, who underwent surgery for non-condylomatous perianal disease over a 2-year period. Of 34 homosexuals 20 presented with anorectal sepsis compared with 11 of 79 heterosexual male patients (X2 = 24.07, P less than 0.001). Lesions included chronic intersphincteric abscess (eight patients), anal fistula (seven patients) and chronic intersphincteric abscess and fistula (five patients). Anal fissure occurred in 15 patients, anal ulcer in three, skin tags in six, haemorrhoids in two and Kaposi's sarcoma in one. Eight patients were human immunodeficiency virus (HIV) antibody negative, four were asymptomatic HIV antibody positive, 12 had symptomatic HIV infection using the Centers for Disease Control classification and in ten patients HIV status was unknown. Irrespective of the type of surgery performed, healing occurred within 6 weeks of operation in all HIV antibody negative patients, all asymptomatic HIV antibody positive and in only one of nine patients with symptomatic HIV infection. Eight of nine patients with symptomatic HIV infection failed to heal by this time (X2 = 8.98, P less than 0.05). These findings suggest that the prevalence of anorectal sepsis in homosexual men is high and that symptomatic HIV infection is an important determinant of progress after surgery. PMID- 2597953 TI - Podophyllin versus scissor excision in the treatment of perianal condylomata acuminata: a prospective study. AB - Thirty-seven patients with previously untreated perianal condylomata acuminata were randomly treated by application of 25 per cent podophyllin or scissor excision. The result of treatment was assessed by an independent observer. At 6 weeks, scissor excision completely cleared the warts from 16 of 18 patients (89 per cent) compared with 15 of 19 patients (79 per cent) treated with podophyllin. Following complete clearance by surgery, two patients had recurrent warts at 18 weeks and a further single patient at 42 weeks, giving a cumulative recurrence rate of 19 per cent. In contrast, five of 15 patients whose warts were cleared by podophyllin had recurrent warts at 18 weeks and a further four at 42 weeks representing a cumulative recurrence rate of 60 per cent (X2 = 3.95, d.f. = 1, P = 0.05). At 42 weeks six patients (32 per cent) were free of disease in the podophyllin group compared with 13 (72 per cent) in the scissor excision group (X2 = 4.6, d.f. = 1, P = 0.03). Scissor excision is therefore preferable to podophyllin application in the treatment of perianal condylomata acuminata. PMID- 2597954 TI - New way to take pinch grafts. PMID- 2597955 TI - Abstracts of papers presented at the ninth meeting of the British Association of Endocrine Surgeons. Lille, France, 26 May 1989. PMID- 2597956 TI - Colorectal cancer and cholecystectomy. PMID- 2597957 TI - Partial cholecystectomy. PMID- 2597958 TI - Perforated peptic ulcer. PMID- 2597960 TI - Paralytic ileus: response to naloxone. PMID- 2597959 TI - Changing concepts in renovascular surgery. PMID- 2597961 TI - Pleomorphic adenomas of the parotid salivary gland. PMID- 2597962 TI - Antibiotic prophylaxis and postoperative sepsis after cholecystectomy. PMID- 2597963 TI - Reducing renal injury during transplantation. AB - Damage sustained by an ischaemic kidney is reduced by cooling the organ. For this reason kidneys are rapidly cooled during the retrieval operation and preserved at low temperature before implantation. When the kidney is removed from cold storage for implantation into the recipient it gradually rewarms (second warm ischaemic time) and a prolonged second warm ischaemic time has been shown to be a cause of acute tubular necrosis following transplantation. The temperature rise in a kidney during implantation has been poorly investigated and little work to minimize that rise has been carried out. This study investigates, in an animal model, the changes that occur in the core temperature of kidneys during the second warm ischaemic time. A jacket has been designed which greatly reduces the rate of kidney rewarming during simulated operative conditions. Kidneys unprotected by the test system showed a rapid rise in temperature from a mean of 1 degrees C to a mean of 20 degrees C after 45 min, compared with those kidneys placed in the protective jacket in which the temperature rose to a mean of only 8 degrees C in the same time. The jacket is not bulky and is simple to use. Maintaining a low kidney core temperature during the second warm ischaemic time will reduce injury to the kidney and should be part of routine clinical practice. PMID- 2597964 TI - Abdominal pain: a surgical audit of 1190 emergency admissions. AB - In an audit of 1190 emergency admissions with abdominal pain (1166 patients) in a general surgical unit, the diagnosis was non-specific abdominal pain (NSAP) in 415 (35 per cent), acute appendicitis in 200 (17 per cent) and intestinal obstruction in 176 (15 per cent). The largest number of admissions occurred in the age groups 10-29 years (31 per cent) and 60-79 years (29 per cent). Surgical operations were performed in 551 patients (47 per cent) and there was a 16 per cent incidence of unnecessary appendicectomy (22 per cent in the age group 20-29 years). Fifty-one deaths resulted in a 30-day hospital mortality rate of 4.4 per cent and a perioperative mortality rate of 8 per cent. The mortality rate increased significantly in patients aged greater than or equal to 60 years, and patients aged 80-89 years had a perioperative mortality rate of 20 per cent. The causes of perioperative death included laparotomy for inoperable disease (28 per cent), ruptured abdominal aortic aneurysm (23 per cent), perforated peptic ulcer (16 per cent) and colonic resections (14 per cent). The perioperative mortality rates for ruptured aneurysm and perforated ulcer were 71 and 23 per cent respectively. The duration of inpatient stay increased significantly with the age of the patients, including those with NSAP. The results of the study indicate a need to review the methods of management of ruptured aortic aneurysm and perforated peptic ulcer, the methods of diagnosis of appendicitis, particularly in young females, and the factors that determine the duration of stay of patients suffering from NSAP. PMID- 2597965 TI - Acute pancreatitis and pancreatic fistula formation. AB - The cause, management and outcome of 23 patients with a pancreatic fistula following acute pancreatitis are reviewed. Nineteen patients developed an external fistula following necrosectomy or drainage of a pancreatic abscess or pseudocyst; four of these patients died. In the 15 survivors spontaneous closure occurred in 11 cases with low output fistulae; operative intervention was needed in the four cases with high output fistulae. Four patients with internal fistulae had not undergone previous surgery; two of them had a pancreaticopleural fistula with associated pancreaticogastric fistulae, while two had pancreatic ascites. All four of these patients required surgical intervention and one died. PMID- 2597966 TI - Surgical treatment of chronic pancreatic cholangiopathy. AB - In a consecutive surgical series of 70 patients with chronic calcifying pancreatitis, 18 presented with fixed stenosis of the terminal common bile duct. Nine patients presented with jaundice and two had a palpable gallbladder. The most relevant laboratory datum in the series was a persistently high serum alkaline phosphatase level. Long tapering of the terminal common bile duct was the characteristic radiological sign in 45 of our patients. In five of the 18 cases compression of the terminal bile duct was due to cephalic pseudocysts. Hepaticojejunostomy-en-Y was the type of drainage chosen in 16 cases, and an end to-side technique was used in 15 patients. Side-to-side choledochoduodenostomy was performed in two cases. In 14 patients, biliary drainage was associated with other surgical procedures on the pancreatic parenchyma. No postoperative complications due to the biliary drainage occurred in this series. PMID- 2597967 TI - Acute pancreatitis after renal transplantation. AB - Post-transplantation pancreatitis is an infrequent complication with a high risk of mortality. In a 7-year period, there were five patients who had documented pancreatitis out of a total of 488 renal homograft recipients, an incidence of 1 per cent. Two cases occurred in patients with an orthotopic transplant, one of them as a result of surgical injury of the pancreas and the other as a consequence of cytomegalovirus infection. The third case was an acute pancreatitis of hypercalcaemic origin, the fourth patient developed postoperative pancreatitis and acute acalculous cholecystitis, and the fifth had acute pancreatitis and sepsis associated with cytomegalovirus infection. Three patients died as a direct result of the complication. The mean incidence and mean mortality rate of post-transplantation pancreatitis, as determined from our review of the literature of the last 15 years, are 2.3 and 61.3 per cent, respectively; these are similar to the figures found up to 1970 of 1.7 and 52.2 per cent. A multiplicity of factors present in the uraemic patient may be responsible for the continued frequency of post-transplant pancreatitis despite advances in surgical technique and immunosuppressive therapy. PMID- 2597968 TI - Surgical audit of patients undergoing common bile duct exploration for stone. AB - One hundred and sixty-four patients operated on for calculus disease of the common bile duct during the period 1977-85 were followed in a special clinic; the attendance for follow-up at 1, 3, 5 and 7 years was 90, 74, 60 and 54 per cent respectively. Eleven patients died during the study period (6.7 per cent), none of the deaths being attributable to biliary tract disease. The overall incidence of retained calculus was 2.4 per cent (four patients), but no cases of retained calculi were recorded in the last 4 years of the study; in this period, with the advent of choledochoscopy and fluoroscopic cholangiography, the incidence of the supraduodenal compared with the transduodenal approach to the common bile duct increased significantly (P less than 0.001). Twenty-two of 56 patients (39 per cent) followed up for 5 years remained or became symptomatic after surgery, the majority of whom had underlying conditions unrelated to disease of the biliary or pancreatic tree. This specific follow-up clinic has been of value in the long term audit of patients undergoing bile duct surgery for choledocholithiasis and it has verified that a change of policy from transduodenal to supraduodenal choledochotomy with preservation of the sphincter, and use of the choledochoscope and fluorocholangiography, produce better results. PMID- 2597969 TI - Mirizzi syndrome and cholecystobiliary fistula: a unifying classification. AB - A new classification of patients with Mirizzi syndrome and cholecystobiliary fistula is presented. Type I lesions are those with external compression of the common bile duct. In type II lesions a cholecystobiliary fistula is present with erosion of less than one-third of the circumference of the bile duct. In type III lesions the fistula involves up to two-thirds of the duct circumference and in type IV lesions there is complete destruction of the bile duct. A total of 219 patients were identified with these lesions from 17,395 patients with benign biliary tract diseases undergoing surgery. The incidence of type I lesions was 11 per cent, type II 41 per cent, type III 44 per cent and type IV 4 per cent. The majority had obstructive jaundice. In type I lesions, cholecystectomy plus choledochostomy is effective. In type II lesions, suture of the fistula with absorbable material or choledochoplasty with the remnant of gallbladder can be performed. In type III lesions suture is not indicated and choledochoplasty is recommended. In type IV lesions, bilioenteric anastomosis is preferred. Operative mortality rate increases according to the severity of the lesion, as does postoperative morbidity. During cholecystectomy, partial resection is recommended in order to extract the stones, visualize the common bile duct and define the type and location of the fistula. T tubes should be placed distal to the fistula. PMID- 2597970 TI - Peptic pyloric stenosis treated by endoscopic balloon dilatation. AB - Twenty-five patients with proven gastric outlet obstruction secondary to peptic ulcer disease were treated by endoscopic balloon dilatation using 'through the scope' balloons. The stricture could not be negotiated in one patient. Two patients continued to have gastric outlet obstruction despite the dilatation and required surgery. Two patients have returned up to 11 weeks after treatment with signs of recurrent gastric outlet obstruction. Twenty patients (80 per cent) remained asymptomatic (follow-up: median 9 months, range 2-24 months). PMID- 2597971 TI - Effects of a somatostatin analogue (SMS 201-995) on the growth and development of hepatic tumour derived by intraportal injection of Walker cells in the rat. AB - Administration of a long active analogue of somatostatin, SMS 201-995 (2 micrograms subcutaneously twice a day) for 3 weeks after intraportal administration of Walker cells significantly inhibited their growth and development in the liver. This was not due to a direct cytotoxic effect of the analogue on Walker cells whose growth was stimulated in vitro. Furthermore, SMS 201-995 had no effect on the growth of Walker cells implanted into the thigh of rats suggesting that the inhibitory action of the analogue could be confined to tumour cells growing in the liver. Further studies suggested that the inhibitory effect of SMS 201-995 on the growth of Walker cells in the liver could be related to a marked stimulation of the hepatic reticuloendothelial system, by a reduction in portal venous flow in the early stages of treatment or by a combination of these effects. Further studies are required to delineate more precisely the mechanism whereby SMS 201-995 inhibits the growth of hepatic tumour derived from intraportal administration of Walker cells. PMID- 2597972 TI - Prognostic value of nucleolar organizer regions and ploidy values in advanced colorectal cancer. AB - The prognostic value of nucleolar organizer regions and ploidy status in patients with Dukes' C colorectal cancer was determined. In addition, nucleolar organizer regions and ploidy status were compared with the established prognostic indices age, sex, tumour location and degree of histological differentiation. Fifty-one patients (27 men, 24 women) aged 35-81 years (median 64.8 years) were studied. Five years after presentation, 16 patients were alive and well. Survivors had significantly lower nucleolar organizer region counts (median value and range) in primary tumours 12 (8-15) and lymph node metastases 11 (8-15) than non-survivors 17 (14-25) and 18 (13-25) respectively (P less than 0.05). Fewer survivors had aneuploid tumours than non-survivors: four survivors compared with 17 non survivors. In a regression analysis model, nucleolar organizer regions were the most important individual variable for predicting survival (chi2 = 15, P less than 0.01) while ploidy values (chi2 = 6, P less than 0.2) were equivalent to histological differentiation. PMID- 2597973 TI - Contralateral inguinal lymph node metastasis in patients with melanoma of the lower extremities. AB - A retrospective study was carried out on six patients with contralateral inguinal lymph node metastasis from a melanoma of the lower extremity. All six patients were found to have had a previous homolateral groin dissection and in five patients there was intercurrent disease relapse in the leg before or at the same time as the appearance of contralateral node metastasis. Although the prognosis in these patients is unfavourable, two had a survival period of 24 and 32 months and two were still alive 27 months after contralateral groin dissection. In order to determine possible pathways of dissemination, lymphoscintigraphic studies of the leg were performed in another 16 melanoma patients who in the past had undergone a groin dissection. In 13 of them uptake in the contralateral inguinal lymph nodes was detected, indicating that groin dissection can lead to a different lymphatic flow pattern, which is often directed to the contralateral groin. Contralateral lymph node involvement may be an expression of regional disease. In such patients a contralateral groin dissection is advocated. PMID- 2597974 TI - Long term results of anorectal myectomy for chronic constipation. AB - Early evaluation of anorectal myectomy in this unit suggested that it might provide clinical benefit to patients with outlet obstruction. Long term results of anorectal myectomy are now available in 63 patients operated on between February 1984 and February 1988 with a median follow-up of 30 months. Spontaneous rectal evacuation without the need for laxatives was recorded in only 11 patients (17 per cent), while 44 (70 per cent) achieved no functional improvement. Mild incontinence developed in 6 patients (10 per cent). Results were independent of preoperative colonic transit or histological evidence of aganglionosis. PMID- 2597975 TI - Function after ileal pouch and stapled pouch-anal anastomosis for ulcerative colitis. AB - Fourteen patients with ulcerative colitis underwent formation of an S ileal pouch and construction of a stapled pouch-anal anastomosis by a modified technique, which eliminated the use of purse-string sutures. Eleven have had their covering ileostomies closed. Anal manometry performed before and a median of 9 months after ileostomy closure showed significant impairment of internal anal sphincter function. Night evacuation was significantly reduced in the stapled group compared with a similar group of patients who had undergone S ileal pouch formation, mucosal proctectomy and manual transanal anastomosis, but this was the only parameter of function to show a difference. A stapled pouch-anal anastomosis may be superior to the conventional procedure but it still may lead to internal anal sphincter damage which cannot be due to mucosectomy or prolonged anal retraction. PMID- 2597976 TI - Lateral internal sphincterotomy in the treatment of fourth degree haemorrhoids. AB - Between January 1984 and May 1988, 25 patients with fourth degree haemorrhoids were treated in the acute phase by lateral internal sphincterotomy under narcosis. Pain relief was immediate. The median hospital stay was 3 days. The median follow-up period was 26 months. For 20 patients a single lateral internal sphincterotomy alone was adequate treatment. If further therapy was required, simple band ligation was enough. There was one recurrence, which was treated with a further lateral internal sphincterotomy. In the long term, 18 patients had no complaints and seven had only minor complaints. Twenty-three patients were very satisfied and two were moderately satisfied. Nobody was dissatisfied. Lateral internal sphincterotomy is an attractive alternative in the treatment of fourth degree haemorrhoids, its major benefits being simplicity, efficiency and low morbidity. PMID- 2597977 TI - Prognosis after surgery for colonic Crohn's disease. AB - The long-term prognosis including operation rates, the incidences of recurrent disease, morbidity and mortality and current status has been analysed in a group of 360 patients with Crohn's colitis grouped according to the primary site of macroscopic disease at diagnosis. The group has been followed from diagnosis for a mean period of 14.9 years. The overall operation rate was 76 per cent. Prolonged spontaneous or drug induced remission occurred at all sites: right sided disease (11 per cent), extensive colonic disease (21 per cent) and left sided disease (38 per cent). The cumulative reoperation rates at 5 and 10 years after right hemicolectomy were 26 and 46 per cent, after colectomy and ileorectal anastomosis 46 and 60 per cent, and after panproctocolectomy 10 and 21 per cent, respectively. There was a twofold excess mortality rate from related Crohn's disease deaths during the period of review, but the mortality rate has fallen with time. There have only been 11 related deaths in the last decade, of which eight were probably unavoidable. The current status of most patients is good, although treatment has included a permanent stoma in less than half (41 per cent) the patients still under review. Currently all but 14 patients are well and symptom-free and only 16 are receiving specific medical treatment. Until the aetiology of Crohn's colitis is understood, if medical treatment has failed to resolve symptoms, appropriate surgical treatment in experienced hands is an effective way of restoring patients with chronic persistent symptoms to good health. PMID- 2597978 TI - Construction of a neorectum and neoanal sphincter following previous proctocolectomy. AB - A new operation is described in which a neorectum and neoanal sphincter mechanism have been constructed to restore gastrointestinal continuity and continence in a patient who had previously undergone proctocolectomy and a permanent ileostomy. The neorectum was constructed by forming a triplicated pouch from the distal ileum. The neoanal sphincter was fashioned from a transposed gracilis muscle and was activated electrically by an implanted stimulator. A period of chronic low frequency stimulation altered the muscle characteristics and enabled the neosphincter to contract continually without fatigue. Complete continence was achieved by the neosphincter gripping a Silastic plug inserted within the efferent spout of the pouch. The patient was able to void completely when the stimulator was switched off and the plug removed. PMID- 2597979 TI - Functional closure of the femoral canal revealed by computed tomographic scanning. AB - The lacuna vasorum contains, as well as the external iliac vessels, a space called the femoral canal which allows pulsation and other changes in the diameter of the two vessels. The canal is closed by a connective tissue septum which is too weak to prevent a herniation alongside the vessels. The functional closure of the canal was investigated by artificial augmentation of the intraluminal pressure of the vein in five specimens and by computed tomographic (CT) scanning during a Valsalva manoeuvre in ten normal persons. In the abdomen the intraluminal and extraluminal pressures are raised in parallel, with no consequence for the diameter of the vessels. In the area of the lacuna vasorum the intravenous pressure is conveyed down to the first competent valve which is located 0.5 cm distal to the inguinal ligament, while the extraluminal pressure is reduced to normal. At each rise of the intra-abdominal pressure the vein will therefore bulge and exactly fill the empty space of the femoral canal thus preventing herniations by an on-demand mechanism. By CT scanning it was found that the vein in the femoral canal increased its diameter 2.5-3.0 times during the Valsalva manoeuvre. PMID- 2597980 TI - Limb conservation for soft tissue sarcomas of the shoulder and pelvic girdles. AB - Fifty-five patients with soft tissue sarcomas of the shoulder and pelvic girdles were treated between 1982 and 1987 with a consistent policy of limb conservation, using a wide variety of excisional and reconstructive surgical techniques and radical radiotherapy. Actuarial 5-year overall survival was 75 per cent for patients with low or intermediate grade tumours, and 38 per cent for those with high grade tumours (log rank test, P less than 0.05). Five-year local recurrence rates were 32 per cent for low or intermediate grade tumours, and 48 per cent for high grade tumours (log rank test, not significant). Multivariate analysis of the following risk factors for overall survival was performed: age, sex, tumour site, diameter, grade, inadequate surgical margins and local recurrence. Age over 55 years and high tumour grade emerged as independent prognostic variables for survival. Forequarter or hindquarter amputations were undertaken in seven of the 55 patients for local recurrence following previous limb-conserving surgery and radiotherapy. Local failure was not always salvaged by major amputation; satisfactory proximal tumour clearance was achieved in only two of seven patients undergoing major amputation; four of the seven patients developed stump recurrence, three of whom died with uncontrolled local disease. Meticulous attention to surgical and radiotherapeutic technique is required to minimize the incidence of local recurrence while maintaining satisfactory limb function. PMID- 2597981 TI - Management of hyperparathyroidism in pregnancy. PMID- 2597982 TI - War wound treatments. PMID- 2597984 TI - Prader-Willi syndrome. PMID- 2597983 TI - Abdominal radical total gastrectomy. PMID- 2597986 TI - Molecular genetics of muscle disease--Duchenne and other dystrophies. PMID- 2597985 TI - Growth factors. PMID- 2597987 TI - The DMD gene analysed by field inversion gel electrophoresis. AB - Genomic and cDNA probes were used to construct a physical map of the DMD region including the 2.3 Mb DMD gene. FIGE-analysis allows rapid screening of the complete region using only a few probes, detecting deletions or duplications in over 60% of the patients. The technique is especially powerful in the analysis of carrier females. We have found two mutational hotspots; a minor hotspot located proximally and a major hotspot within a large, centrally located intron. Deletions involving this latter intron were studied using 100 kb of cloned DNA sequences. Although breakpoints are spread over the entire region, 5 are clustered within 3 kb. Analysis of over 250 BMB/DMD families has underscored the importance of germinal mosaicism as a major diagnostic pitfall. At least 14% of new mutation cases involve germinal mosaicism and this still is a lower estimate, due to small family sizes. Hence, relatives of apparent new mutation patients should be considered to have high risk, and require appropriate counselling. PMID- 2597988 TI - Molecular genetics of muscle disease--Duchenne and other dystrophies. Future prospects. AB - In the last few years the biochemical lesion in Duchenne/Becker Muscular Dystrophy has been discovered and the gene for the missing/abnormal protein (dystrophin) has been cloned. The implications of these discoveries on the prospects for diagnosing and eventually eradicating this disease and for the possible treatment of affected boys are discussed. PMID- 2597989 TI - The natural history of multiple sclerosis: a geographically based study. 2. Predictive value of the early clinical course. AB - Controversy exists regarding the predictive value of the early clinical course of multiple sclerosis (MS). Three parameters often considered are the attack rate, the first interattack interval and the rate at which disability develops in the early years of the disease. We have recorded the time to reach successive levels of disability defined by the Kurtzke Disability Status Scale (DSS) in 1,099 MS patients followed at University Hospital, London, Canada between 1972 and 1984. Our population is particularly suitable because of its size, the high degree of ascertainment of cases in the community, and the regular follow-up provided. Life table analysis was used to compare survival in patients stratified according to the above three parameters using DSS 6 as end point. Significant differences were evident in the survival distributions. Despite the extensive interindividual variation in the rate at which disability developed, the early course of MS may be useful in determining the relative risk of rapid progression. PMID- 2597991 TI - Loss of memory for people following temporal lobe damage. AB - A 40-yr-old woman, K.S., is reported, who shows a severe loss of memory for people following a history of epilepsy and right anterior temporal lobectomy. Despite this memory problem, K.S. is not clinically amnesic, has a Memory Quotient of 122 on the Wechsler Memory Scale in line with her IQ of 119, and performs well on conventional tests of recognition and recall. She does not have a generalized semantic memory deficit for living things, but her deficit extends beyond people to include famous animals, buildings and product names. Autobiographical memory is good, except where memory for people is concerned. The nature of the memory store that is impaired in K.S. is discussed, as are the implications of her case for theories of the organization of long-term memory. PMID- 2597990 TI - Multiple sclerosis amongst Chinese in Hong Kong. AB - A territory-wide investigation of southern Chinese patients with multiple sclerosis (MS) was conducted in Hong Kong. There were 47 patients, 35 of whom were clinically definite (CDMS), 6 laboratory-supported definite (LSDMS) and 6 clinically probable (CPMS). The prevalence rate was 0.88 per 10(5) population, which is of the same order as in other Oriental populations but much lower than in Caucasoid populations. Comparisons with major Oriental and Caucasian series showed essentially the same clinical picture with only minor variations. In one autopsy case, the lesions were found mainly in the optic nerves and spinal cord, with marked softening in addition to the classical demyelination features. In contrast to findings in Caucasians, the detection rate of oligoclonal bands in the cerebrospinal fluid was low (33% in CDMS patients) and there was no association with human leucocyte antigens. The possible implications of these findings on the pathogenesis of MS are discussed. PMID- 2597992 TI - Visuospatial processes of line bisection and the mechanisms underlying unilateral spatial neglect. AB - Patients with unilateral spatial neglect fail to report or respond to stimuli contralateral to the lesion which usually involves the right parietal lobe. When asked to mark the centre of a horizontal line, these patients place the mark to the right of the true midpoint. It has been considered that they neglect the left part of the line and bisect the perceived line segment. We investigated the eye fixation patterns of hemianopic patients with or without unilateral spatial neglect during the bisection of lines, using an eye camera. Hemianopic patients without unilateral spatial neglect saw the whole lines, searching to the endpoint on the hemianopic side, and bisected it correctly. In contrast, left hemianopics with unilateral spatial neglect never searched to the left hemianopic side. Once they fixated a certain point on the right part of the line, they persisted with this point and marked the subjective midpoint there. Taking left homonymous hemianopia into account, the subjective midpoint appeared to be marked, not at the centre of the line segment perceived in the seeing right visual field, but at the leftmost point of it. However, they could appreciate the deviation of the subjective midpoint in the right visual field when forced to fixate the left endpoint of the line. These findings suggest that the left hemisphere has the ability to estimate the midpoint of the line through the right visual field and that visuospatial disorder in the line bisection test is attributable to the pathological change in the right hemisphere. The results are interpreted to mean that left hemianopic patients with unilateral spatial neglect see a totalized image of a line extending equally to either side of the point where they are going to mark the subjective midpoint. We considered that the right hemisphere completes the line, using the visual input relating to the right part of the line perceived by the left hemisphere. PMID- 2597993 TI - Nonverbal recognition and recency discrimination deficits in Parkinson's disease and Alzheimer's disease. AB - In a study of verbal temporal ordering, patients with Parkinson's disease (PD) were impaired in making judgements of the relative recency of serially-presented words but were normal in word recognition; by contrast, patients with Alzheimer's disease (AD) were impaired on both verbal tasks (Sagar et al., 1985, 1988b). The present study used a nonverbal analogue of the verbal temporal ordering task to examine whether the deficit in recency discrimination of the PD patients transcended material-specific bounds or was specific to verbal material. The nonverbal task was administered to the patients with PD, patients with AD and normal control subjects studied with the verbal task. The results showed that the retention functions for the recognition of verbal and nonverbal material differed qualitatively from each other and this difference was present in all three subject groups. For verbal and nonverbal recency discrimination and verbal content recognition, performance declined with increasing retention intervals; for nonverbal content recognition, however, performance was essentially unchanging across retention intervals. As on the verbal test, recency discrimination on the nonverbal test was impaired in both patient groups. In contrast to the results with the verbal task, both groups were impaired on content recognition. The patterns of impairment, however, differed between the two patient groups in a parallel way to those of the verbal task: performance of the AD group was impaired at the longest retention intervals but not at the shortest intervals, whereas the performance of the PD group was impaired at the shortest but not at the longest intervals. This deficit in nonverbal short-term recognition memory was present even in PD patients who scored within the normal range on a quantitative test of dementia. These results show that deficits in recency discrimination and short-term memory processing in PD extend to nonverbal as well as verbal material and imply bilateral frontal lobe dysfunction in the genesis of these deficits. PMID- 2597994 TI - Conduction velocities of muscle and cutaneous afferents in the upper and lower limbs of human subjects. AB - In the cat and monkey the fastest axons in the peripheral nerve are group I afferents from muscle, but there are no definitive data on conduction velocity for these afferents in human subjects. Knowledge of the relative conduction velocities of muscle and cutaneous afferents is important for the interpretation of reflex studies, evoked potentials and other aspects of motor control. To rectify this deficiency, the conduction velocities of the fastest muscle and cutaneous afferents were determined for the median, ulnar and tibial nerves of normal subjects. Low-threshold muscle afferents innervating abductor pollicis brevis, abductor digiti minimi and abductor hallucis were stimulated selectively through a microelectrode inserted percutaneously at the motor point. Low threshold cutaneous afferents were stimulated with ring electrodes around the proximal phalanx of digits II or V for the upper limb and digit II for the lower limb. Compound action potentials were recorded with bipolar near-nerve electrodes at two sites in the proximal limb segment and conduction velocities of the fastest afferents in the neural volley calculated. The mean conduction velocities of the muscle and cutaneous afferents were, respectively, 74.7 +/- 6.5 m.s-1 and 80.3 +/- 6.7 m.s-1 for the median nerve, 67.5 +/- 10.2 m.s-1 and 67.5 +/- 10.5 m.s-1 for the ulnar nerve, and 54.7 +/- 3.4 m.s-1 and 52.8 +/- 3.2 m.s-1 for the tibial nerve. For upper and lower limb nerves the conduction velocities of low threshold muscle and cutaneous afferents were not significantly different when measured over the same proximal segment. PMID- 2597995 TI - The role of the subthalamic nucleus in experimental chorea. Evidence from 2 deoxyglucose metabolic mapping and horseradish peroxidase tracing studies. AB - In previous studies we have shown that hemichorea can be induced in the conscious monkey by localized injection of gamma-aminobutyric acid (GABA) antagonists into the contralateral lentiform complex. It has been argued that the primary site of drug action in inducing chorea is the lateral segment of the globus pallidus. In the present study, the neural mechanisms which underlie this experimental dyskinesia were investigated by two separate approaches. First, the efferent projections of the lentiform complex were mapped using neuroanatomical tracing techniques. This involved injecting horseradish peroxide into sites which had previously given chorea when injected with the GABA antagonist bicuculline. Secondly, the 2-deoxyglucose (2-DG) metabolic mapping technique was applied to animals during active dyskinesia. This procedure permitted the autoradiographic measurement of local cerebral glucose uptake which was used as an index of regional synaptic activity. In both instances, the strongest labelling was seen in the dorsolateral region of the subthalamic nucleus. On the basis of this finding it is suggested that the pallidosubthalamic pathway plays a crucial role in the mediation of experimentally-induced chorea. Specifically, the pallidosubthalamic pathway arising from the lateral pallidal segment is abnormally overactive, which causes physiological inhibition of the subthalamic nucleus. The pattern of 2-DG uptake in the medial segment of the globus pallidus and thalamus was similar to that seen in animals with experimentally-induced ballism. This similarity is interpreted as suggesting that a common neural mechanism underlies both experimentally-induced chorea and ballism. PMID- 2597996 TI - Lexical agraphia in the Japanese language. Pure agraphia for Kanji due to left posteroinferior temporal lesions. AB - A new syndrome of 'pure agraphia for Kanji' is described in 3 Japanese subjects with lesions in the left posteroinferior temporal region. Kanji (ideogram or morphogram) can be compared with orthographically irregular or ambiguous words in some European languages, since it is impossible to write Kanji characters unless each one of them is learned and memorized. In contrast, Kana (phonogram or syllabogram) words are comparable with orthographically regular words or nonsense words, because the Kana writing system depends on strict phonological rules (almost one-to-one correspondence between syllable and syllabogram). We conclude that 'lexical agraphia' reported in European languages can also be observed in the Japanese language where it is expressed as 'pure agraphia for Kanji'. 'Lexical agraphia' is a useful concept with general application regardless of language system. PMID- 2597997 TI - Chronic inflammatory demyelinating polyneuropathy. Conduction failure before and during immunoglobulin or plasma therapy. AB - An earlier study has shown that patients with chronic inflammatory demyelinating polyneuropathy may improve after the infusion of fresh frozen plasma or high dose intravenous immunoglobulin. We studied 8 such responding patients with neurophysiological techniques. Before treatment all patients had decreased compound muscle action potentials (CMAP) and slowing of conduction. During several courses of treatment a progressive increase of the CMAPs occurred and in 5 patients a correlation between the CMAPs of the abductor pollicis brevis muscle and grasp force could be demonstrated. In 2 patients, increase in strength was correlated with shortening of the distal motor latency; no significant relationships were found between strength and conduction velocity. Different patterns in the distribution of conduction failure were observed. In 2 patients, lesions were distributed along the length of the motor fibres, whereas the sensory system was spared. In another 2 patients the lesions, most likely demyelinating, were localized distally and included the sensory system. The 4 remaining patients were more difficult to classify, but individually showed greater resemblance to one or other of the two described patterns. Different patterns of conduction failure may reflect different pathogenetic mechanisms. PMID- 2597998 TI - Abnormalities of nonvisually-guided eye movements in Parkinson's disease. AB - Rapid eye movements (saccades) were examined in 7 patients with idiopathic Parkinson's disease (PD) and a matched group of normal control subjects. The effect of instructional and stimulus conditions used to elicit saccades was examined using 3 experimental paradigms. Eye movements directly elicited by a novel peripheral target were unimpaired in patients with PD as compared with control subjects. Saccades to a remembered target location, however, were dysmetric in the PD group and showed a characteristic multistepping pattern. The PD impairment was not caused by a loss of information on target location since their final eye position was close to the target at all eccentricities. Peak velocity, duration, and latency did not distinguish between PD patients and controls. These results support the view that for saccades which are not directly elicited by a visual target there is a neural pathway that can be distinguished from structures involved in the generation of visually elicited (or 'reflexive') saccades. The finding that in PD saccades to a remembered target are selectively impaired suggests that structures in the basal ganglia play a crucial role in this alternative pathway. PMID- 2597999 TI - The origins of utilization behaviour. AB - Utilization behaviour has previously been described clinically by Lhermitte (1983). An experimental investigation is reported of utilization behaviour in a patient with a localized inferior medial bifrontal lesion. The patient picked up and used irrelevant objects not only when place directly in front of him--the procedure developed by Lhermitte--but also when he had been instructed to carry out other tasks and his attention had not been directed to the objects. The behaviour occurred most frequently in the brief intervals between tasks, and more often when auditory-verbal rather than visuomotor tasks were being performed. The results are interpreted within an information-processing model of frontal lobe function. A differentiation is made between two forms of utilization behaviour- an 'incidental' form, as exhibited by the patient, and an 'induced' form where it occurs only when Lhermitte's procedure is adopted. PMID- 2598000 TI - Sensorimotor disturbances in patients with lesions of the parietal cortex. AB - Somatosensory and motor disturbances of hand function were examined in 9 patients with parietal lobe lesions. A quantitative score was used for the elaboration of sensorimotor profiles displaying the relative degree of functional impairment. In patients with anterior parietal lobe lesions somaesthesis was clearly more disturbed than motor function. Simple aspects of somaesthesis (surface sensibility, two-point discrimination, position sense) were disturbed to about the same degree as complex somatosensory (tactile recognition) tasks. On the other hand, patients with lesions of the posterior parietal lobe showed preferential impairment of complex somatosensory and motor functions (exploratory and manipulative finger movements). In 4 patients, analysis of motor behaviour by means of an optoelectronic system showed that reaching, formation of hand aperture and target acquisition were less disturbed than manipulative behaviour. Finger movement trajectories during dynamic digital palpation of objects were grossly deranged in the patients with posterior parietal damage. The temporal characteristics of the finger movements during active touch were completely destroyed. This leads to a breakdown of the finely tuned digital scanning process required for the sequential sampling of mechanoreceptive information. Remarkably, these patients could produce the exploratory finger movements imitatively. The motor disability of the parietal hand does not lie in the loss of the kinetic memory to perform these movements, but in the loss of their evocation by appropriate sensory stimuli. This deficit is not due to a lack of somatosensory information because that may be relatively well preserved. It is concluded that the motor disturbance in posterior parietal lobe disease lies essentially in the conception and execution of the spatiotemporal movement patterns necessary to bring those receptors into action which would normally provide the information about tactile objects. This illustrates the intricate mutual dependence of the spatiotemporal organization of receptor activation by movement and of the formation of movement trajectories on the basis of adequate sensory processing. PMID- 2598001 TI - Influence of response modality on perceptual awareness of contralesional visual stimuli. AB - Visual extinction on double simultaneous stimulation was investigated in left and right brain-damaged patients in two response conditions: verbal and motor. In right brain-damaged patients contralesional detection was significantly worse when monitored by motor rather than by verbal responses in condition of single as well as of double stimulation. Previous research in normal subjects had shown that the left hemisphere is selectively involved in choice reactions such as those occurring in the motor condition of the present experiment in brain-damaged patients. The results of the latter are interpreted using as a basis the findings of that research and Kinsbourne's hemisphere activation hypothesis concerning unilateral neglect of space. PMID- 2598002 TI - Cognitive event-related potentials in multiple sclerosis. AB - Twenty-three patients with multiple sclerosis (MS) and 1 patient with isolated optic neuritis (mean age 37.5 yrs, average duration of disease 10 yrs) were tested with auditory and visual cognitive event-related potentials (ERPs) using an oddball paradigm. The results were compared with data from 19 age-matched healthy controls. All patients had magnetic resonance imaging (MRI) head scans and 19 had comprehensive neuropsychological testing. The stimulus-related components of the ERPs were normal for nearly all patients, but 10 showed abnormalities of the later cognitive-related components and another 3 had waveforms in which the cognitive components could not be identified. These abnormalities were found mainly for the auditory test. Of these 13 patients, 11 had significantly prolonged reaction times (RT) or reduced target recognition performance. Five of 8 MS patients with normal IQ and memory function tests had abnormal ERPs with the reverse being true for 4 of 10 patients. Patients with abnormal ERPs showed a higher MRI cerebral lesion score and had a longer duration of illness and greater physical disability than patients with normal ERPs. It is concluded that the generation of ERPs is in part dependent on the integrity of cerebral white matter and that ERPs may indicate subtle degrees of cognitive dysfunction not always detected by standard tests of intellect. PMID- 2598003 TI - Neurochemical and behavioral correlates of unilateral striatal acetylcholinesterase inhibition by fasciculin in rats. AB - Fasciculin 2 (FAS) an anticholinesterase peptide isolated from the venom of the Green mamba (Dendroaspis angusticeps) was injected into the right striatum of albino rats (1.5 micrograms total amount). The inhibition of acetylcholinesterase (AChE) activity was 86 and 60% 24 h and 7 days after FAS injection, respectively. The treatment with apomorphine (APO) (2 mg/kg s.c.) 24 h after FAS provoked a moderate circling towards the lesioned side that was reverted by atropine (30 mg/kg i.p.). The same dose of APO 7 days after FAS, provoked an inconstant contralateral circling. Neither dopamine nor serotonin nor their metabolites were significantly affected 24 h or 7 days after FAS injection. Radioligand binding assays of dopamine, muscarinic and benzodiazepine receptors only showed a decrease of the density of the muscarinic ones 7 days after FAS. These results are interpreted as showing that the changes provoked by FAS would be compensated but the system would remain in an unsteady state only demonstrable after pharmacological challenge. The chronic down-regulation of muscarinic receptors would compensate the increased cholinergic activity and would therefore block its behavioral expression. PMID- 2598004 TI - Local cerebral glucose utilization following subacute and chronic diazepam pretreatment: differential tolerance. AB - Local cerebral glucose utilization (LCGU) was determined in parallel groups of conscious rats receiving diazepam (0.3 mg/kg i.v.) either acutely or following subacute (5 mg/kg i.p. daily for 3 days) or chronic (5 mg/kg i.p. daily for 28 days) diazepam pretreatment, using 2-deoxyglucose quantitative autoradiography. Acute administration of diazepam reduced LCGU in 44 of the 66 structures examined compared to vehicle-treated controls. These included limbic, cortical and extrapyramidal structures, and areas associated with sensory processing. These data are consistent with many brain regions being functionally involved in the diverse acute pharmacological effects of diazepam and with the widespread distribution of benzodiazepine receptors throughout the neuroaxis. Following subacute treatment, when animals were tolerant to the sedative effects of diazepam, glucose use remained depressed in the majority of areas studied. However, in the locus coeruleus, dorsal tegmental nucleus and most structures associated with auditory processing, tolerance to the depressant effect of diazepam upon glucose use had occurred suggesting the importance of these structures in the sedative effect of diazepam. The most striking feature of the patterns of LCGU after chronic diazepam treatment was that tolerance had occurred in the mammillary body and subiculum. However, glucose use remained depressed in hippocampal layers and in structures that provide input to the hippocampus (e.g. raphe nuclei). These data suggest that the outflow of neuronal activity from the hippocampus to the mammillary body via the subiculum is restored after chronic treatment, and may implicate these pathways in the anxiolytic action of diazepam. Overall, it would appear that different neuroanatomical substrates underlie the various pharmacological effects of diazepam and that there may be regional differences in tolerance mechanisms. PMID- 2598005 TI - Ouabain selectively affects the slow component of sensory adaptation in an insect mechanoreceptor. AB - Sensory activity in the cockroach tactile spine neuron adapts rapidly to a step deflection. This rapid adaptation is caused by a rise in the threshold for action potential production, which has two components with different time constants and drug sensitivities. The basis of the slow component is unknown but it is insensitive to a wide range of ion channel blockers. In the present experiments the slow component was selectively reduced by ouabain, suggesting that it is due to the activation of an electrogenic sodium pump. PMID- 2598006 TI - Effect of a brief hypoxic/hypotensive episode on the in vivo release of cerebral cortical gamma-aminobutyric acid and glycine. AB - gamma-Aminobutyric acid (GABA) and glycine levels in rat cerebral cortical superfusates rose during a 10-min period to reach stable concentrations of approximately 0.55 microM and approximately 12.3 microM, respectively. In cerebrospinal fluid withdrawn from the fourth ventricle, the GABA concentration was 0.1 microM, and that of glycine, 10.55 microM. GABA, and to a lesser extent glycine, concentrations increased in the cortical superfusates during and immediately following exposure of the rats to a 5-min period of 5% oxygen in nitrogen inhalation. PMID- 2598007 TI - Interaction between the serotonin and dopamine systems in humans: preliminary findings. AB - The availability of peripheral tools, such as platelet [3H]-imipramine binding and electroretinogram b-wave amplitude, for investigating serotonin and dopamine systems respectively, prompted us to explore the possible relationships between these two systems in a group of 8 healthy drug-free volunteers. The results showed a significant correlation between the peripheral parameters of serotonin and dopamine systems and underline the importance of studying different neurotransmitters at the same time in humans. PMID- 2598008 TI - Veratridine stimulation of sodium influx in carotid body cells from newborn rabbits in primary culture. AB - It was examined whether or not 22Na+ influx into cultured cells of the carotid body (CB) from newborn rabbits might be stimulated by veratridine (VRT), using superior cervical ganglion (SCG) cells as a standard, showing the VRT-stimulating effects on 22Na+ influx. In a CB glomus cell-rich culture, VRT induced a 22Na+ influx increase, as seen in a SCG neuronal cell-rich culture, which was entirely inhibited by tetrodotoxin (TTX). In contrast, in a CB non-glomus cell culture as well as in a SCG non-neuronal cell culture, the VRT-stimulating effect was not seen. This indicates that the VRT-stimulating effect found in the CB glomus cell rich culture was evoked from only glomus cells. It is concluded that glomus cells have TTX-sensitive voltage-dependent sodium channels, which might be indirectly involved in the chemotransduction mechanism in the CB. PMID- 2598009 TI - Cells of origin of histaminergic afferents to the cat median eminence. AB - The exact origin of histaminergic neuronal perikarya sending axons to the median eminence and posterior pituitary was investigated in the cat by using two colour double-immunostaining methods: unconjugated wheat germ agglutinin or cholera toxin as retrograde tracers combined with histamine (HA) immunohistochemistry. HA immunohistochemistry revealed the presence of HA-immunoreactive terminal-like fibers both in the external layer of the median eminence and neural lobe of the pituitary. The double-labeling studies further demonstrated the histaminergic innervation of the median eminence and neural lobe by a few HA-immunoreactive neuronal perikarya located in the posterior hypothalamus. PMID- 2598011 TI - Glia maturation factor-beta promotes the appearance of large neurofilament-rich neurons in injured rat brains. AB - Adult rat brains were injured by partial decortication. Glia maturation factor beta (GMF-beta) was applied to the wound cavity 3 times over a period of two months. At the end of the experiment, brain sections were prepared and immunostained for neurofilaments. Large, neurofilament-rich neurons were observed in clusters in the brain tissue adjacent to the wound cavity. These neurons displayed prominent apical dendrites, some of which grew out branches toward the direction of the wound. The results suggest that GMF-beta promotes the hypertrophy of selective neurons in the injured cerebral cortex and implies a role for GMF-beta in central nervous system regeneration. PMID- 2598010 TI - Connectivities of the striatal grafts in adult rat brain: a rich afference and scant striatonigral efference. AB - Previous reports from this laboratory have indicated that fetal rat striatal grafts have the major types of neuronal and glial components known to be involved in Huntington's chorea. In this study a number of major afferent and efferent innervations seen in normal striatum were examined in the striatal grafts and were compared with embryonic striatal afferents. First, using immunocytochemistry and histochemistry, the host serotonergic (5-HT), dopaminergic (DA, stained with anti-tyrosine hydroxylase (TH) antiserum), and acetylcholinesterase (AChE) fibers exhibited vigorous growth into the grafts implanted in neostriatum, lateral ventricle, globus pallidus or substantia nigra within a period of 6 and 10 weeks. Individual characteristic terminal patterns formed in striatal grafts: 5-HT fibers were diffused; TH fibers became heavily packed, and AChE fibers were patchy. This peculiar patternization of 5-HT and TH growth into striatal graft appeared to be a recapitulation of the normal 5-HT and TH ingrowth into striatum in the embryonic stage. However, a significantly slow (6 week) onset of adult 5 HT and TH ingrowth into the fetal graft was noted, as compared with that of normal embryonic development (5-6 days from the appearance of 5-HT and TH neurons). With the anterograde-transport marker Phaseolus vulgaris agglutinin leuca method, host cortical neurons also projected to the graft, but in limited numbers. Finally, with the retrograde-transport marker (horseradish peroxidase method, the grafts implanted in neostriatum were found incapable of sending fibers to a major, distal target, substantia nigra. In a current evaluation of striatal transplants, it is shown that major input to the graft can be achieved over time, but output to the distal nigra seems an unrealistic expectation. These data suggest that: (1) the fetal brain tissue was found to be a strong stimulant for sprouting or regeneration of adult nerve fibers; (2) a number of functional recoveries reported on the tested behavior paradigm in this grafting model could be due to the survival of striatal graft and the establishment of input circuitries; further, (3) the data illustrate the necessity of seeking a bridge from the striatal transplant to the host nigra. If a proper functional recovery in Huntington's chorea requires complete striatonigral circuitry, then such a bridge is worthy of a major investigation. PMID- 2598012 TI - Confocal laser microscopy to study microcirculation on the rat brain surface in vivo. AB - We demonstrate the feasibility of using confocal laser microscopy (CLM) to study the microcirculation on the rat brain surface. Using a closed cranial window model in vivo, microvessels in the size range of capillaries (8 microns) and dynamic events were observed through an intact dura. This study is the first step in the development of a system which simultaneously monitors vascular and metabolic processes using CLM. PMID- 2598013 TI - Lack of the suckling-induced prolactin release in homozygous Brattleboro rats: the vasopressin-neurophysin-glycopeptide precursor may play a role in prolactin release. AB - Suckling stimulus did not induce significant release of prolactin (PRL) in lactating homozygous Brattleboro rats, whereas it did it in heterozygous animals. Daily treatment of homozygous rats with vasopressin partly restored the PRL response to suckling. Findings suggest that vasopressin-neurophysin-glycopeptide precursor missing in homozygous Brattleboro rats may play a role in suckling induced PRL release. PMID- 2598015 TI - Localization, origin and fine structure of calcitonin gene-related peptide containing fibers in the vestibular end-organs of the rat. AB - The localization, origin and fine structure of nerve terminals immunoreactive for calcitonin gene-related peptide (CGRP) were examined in the vestibular end-organs of rats using immunocytochemistry. Many CGRP-like immunoreactive (CGRP-IR) fibers were observed in the vestibular sensory epithelial layer. By electronmicroscopy, CGRP-IR terminals were found to make synaptic contacts with the chalyces of the vestibular nerves terminating on type I cells. The origin of these vestibular CGRP-IR fibers was examined by a combination of a retrograde fiber tracing technique (using Fast blue) and immunocytochemistry. Injections of the tracer into the vestibular cistern, resulted in fast blue-labeled neurons bilaterally in the area dorsolateral to the genu of the facial nerve; these labeled neurons also contained CGRP. These findings indicate that CGRP-IR fibers originate bilaterally from the area dorsolateral to the genu of the facial nerve and that CGRP plays a modulatory role in the transmission of vestibular information from type I cells. PMID- 2598014 TI - Cerebrovascular and metabolic perturbations in delayed heavy charged particle radiation injury. AB - Focal heavy charged particle irradiation of the rabbit brain created defined lesions which were observable by nuclear magnetic resonance (NMR) and positron emission tomography (PET) imaging techniques. The lesions appeared approximately 9-11 months after left partial hemibrain irradiation with 30 Gy (230 MeV/u helium ions), and were restricted to the white matter tracts and deep perithalamic and thalamic regions. 82Rubidium PET and Gadolinium DTPA enhanced NMR imaging were used to detect blood-brain barrier perturbations. 18Fluordeoxyglucose PET studies demonstrated widespread decreases in cerebral glucose uptake in the cortex and thalamus of the irradiated hemisphere. NMR and PET imaging results correlated well with histological findings. Rabbits irradiated with 15 Gy did not demonstrate any abnormalities in the brain with sequential NMR scans through 14 months post-irradiation. PMID- 2598016 TI - Localization of a leech inhibitory synapse by photo-ablation of individual dendrites. AB - An inhibitory motor neuron (cell 1) in the leech nervous system has a powerful inhibitory connection onto an excitatory motor neuron (cell 3) that is functionally important in behaviours such as swimming and local bending. The anatomical location of this connection was explored using focal ultraviolet irradiation of cell 3 dendrites filled with Lucifer yellow. Ablation of the main neurite of cell 3 in the middle of the ganglion eliminated 72% of the inhibitory postsynaptic potential (IPSP), showing that most of the synaptic contacts are in the dendritic field contralateral to the cell body. Ablation of a particular dendritic branch (d1), one of several that run anteriorly from the main neurite in the contralateral ganglion, eliminated 70% of the IPSP in some cases but only 4% in others. In these latter cases, subsequent ablation of a more distal dendrite (d2) eliminated from 41% to 83% of the IPSP. These findings suggest that the synapses onto cell 3 from cell 1 are primarily mediated by either one of these dendrites or the other, but not both. This synaptic specificity might be due to a developmental mechanism involving competition between dendrites for occupation of synaptic sites. PMID- 2598017 TI - Catecholamine uptake sites in mouse brain: distribution determined by quantitative [3H]mazindol autoradiography. AB - Because of the importance of the mouse brain catecholamine system in the study of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and because little information is available concerning the chemical neuroanatomy of the mouse, catecholamine uptake sites were mapped in C57 black mouse brain using [3H]mazindol autoradiography. Displacement studies with known dopamine (DA) and noradrenaline (NA) uptake blockers showed that binding in the striatum was entirely to DA uptake sites, while binding in the locus coeruleus was to NA uptake sites only. By using the selective noradrenergic uptake blocker desmethylimipramine (DMI), a complete map of both DA and NA uptake sites was generated. The mesostriatal DA system was the most clearly labelled and uptake sites were seen better in striatal terminals than the substantia nigra. Within the noradrenergic system, highest binding levels were seen over the locus coeruleus, although it was unclear whether these uptake sites were on cell bodies or terminals from the lateral tegmental noradrenergic system. These maps of the catecholamine uptake system in mouse brain provide a baseline for study of newly discovered neurotoxins and ageing processes. PMID- 2598018 TI - Resistance of astrocyte electrical membrane properties to acidosis changes in the presence of lactate. AB - The membrane potential and input resistance of mouse astrocytes in primary cultures were measured with two-channel microelectrodes. It was found that 30 mM sodium lactate (no pHo change) caused a hyperpolarization of 5 mV. A stepwise reduction in pH via HCl addition had no effect at pHo 6.5, at pHo 5.5 there was a 5 mV depolarization and at pHo 4.5 the membrane depolarized by 28 mV and the input resistance increased by 4.9-times. After 20 min this change was still reversible. If the pHo was lowered by the addition of lactic acid, a pHo of 4.5 (30 mM lactic acid) caused a 45 mV depolarization and a 4.3-times increase in input resistance. Exposure to these conditions caused irreversible effects. The exposure time for a 50% recovery of the membrane potential was 15 min. The results show that external acidification (for a period of 20 min) is only irreversible if lactate is present, probably due to excessive H+ shifts into the cells via the H+-lactate carrier. The results are of significance to explain glial damage during incomplete ischemia. PMID- 2598019 TI - Actions of brain-protecting substances against both oxygen and glucose deprivation in the guinea pig hippocampal neurons studied in vitro. AB - A study was made of the protective effects of several drugs (mannitol, phenytoin, vitamin E and dexamethasone) on the electrical activities of guinea pig hippocampal neurons in vitro when they were treated with a bathing medium deprived of both oxygen and glucose. Using guinea pig hippocampal slices, antidromic field potentials in the granular cell layer of the dentate gyrus were recorded stimulating mossy fibers. A model of ischemia in vivo in the slices was achieved by removing both oxygen and glucose from the perfusing medium. In standard medium, after 10 min of both oxygen and glucose deprivation, the field potentials exhibited minimum recovery with an amplitude of 6% of the control after 60 min. The protective effect of the drugs was evaluated by recovery of the field potential amplitude of the 60 min post-deprivation response and histological examination of the brain slice tissue. Drugs were added during 30 min of pre-deprivation and during deprivation. In this experiment we demonstrated that (1) phenytoin and vitamin E clearly showed protective action against neuronal damage caused by both oxygen and glucose deprivation in guinea pig hippocampal slices, (2) combined application of these drugs was more effective, and (3) mannitol showed no protective action in vitro. It was also demonstrated that (4) the dentate antidromic field response can be a useful index of cell death. PMID- 2598020 TI - Neuronal loss and neuronal atrophy. Computer simulation in connection with Alzheimer's disease. AB - A decrease in the number of neuronal profiles in the isocortex of man may be observed on microscopic sections in aging and in degenerative diseases such as Alzheimer's disease. It can be the consequence of a loss of neurons per unit volume or of a reduction of the neuronal volume (i.e. pseudo-loss). This latter possibility has been tested by simulating neuronal atrophy, with sections of various thicknesses. An unfolding algorithm was used for the simulation. The data published in the current literature concerning Alzheimer's disease were treated with the unfolding algorithm. The neocortical pseudo-loss did not exceed a few percentage points, probably much less than the measurement error. New methods of cell counting have been recently proposed to discriminate real from pseudo-loss. They should be used when the risk of dealing with pseudo-loss is high. A chart to assess the percentage of pseudo-loss as a function of perikaryal atrophy is proposed: it relies on the evaluation of the size of the cell relative to the section thickness (relative caliper diameter). This chart may be used to correct cell counts of homogeneous cell populations. PMID- 2598022 TI - A general role for serotonin in the control of behavior: studies with intracerebral 5,7-dihydroxytryptamine. AB - Multiple injections of 5,7-dihydroxytryptamine (5,7-DHT) into the rat brainstem reduced forebrain levels of serotonin and 5-hydroxyindoleacetic acid to 3-10% of the levels observed in control rats that had received intrabrainstem injection of a Locke's solution vehicle. This treatment reduced or abolished atropine resistant cerebral activation (ARCA) in most cases. In rats in which ARCA was impaired or lost, a number of behavioral abnormalities were observed. These included: high levels of locomotion in an open field test; a deficiency in swimming to, and climbing upon, a visible platform in a water-filled tank; deficient social behavior; and impaired performance in a simple test of active avoidance. These deficits were not due to low level motor impairment. The 5,7-DHT treated rats displayed a circadian rhythm of activity in running wheels. It is proposed that ascending serotonergic projections are an important component in the cerebral control of the Type 1 behavior with which the occurrence of ARCA is closely linked. Since Type 1 behavior includes such motor patterns as walking and manipulation of objects with the limbs, which are essential components of a great variety of behavioral performances, it is to be expected that a loss of ascending serotonergic function will result in a generalized deficit in behavior. PMID- 2598021 TI - The role of serotonin in the control of cerebral activity: studies with intracerebral 5,7-dihydroxytryptamine. AB - Intact rats treated with centrally acting antimuscarinic (atropinic) drugs display large amplitude irregular slow waves in both the neocortex and hippocampus during behavioral immobility and some stereotyped automatic behaviors (Type 2 behavior). However, rhythmical slow activity in the hippocampus and low voltage fast activity in the neocortex occur in close correlation with spontaneous changes in posture, head movement, walking, rearing, swimming or struggling when held (Type 1 behavior). It has previously been proposed that these waveforms, jointly referred to as atropine-resistant cerebral activation (ARCA) are dependent on ascending serotonergic projections. As a further test of this hypothesis, we have studied rats in which forebrain levels of serotonin and 5-hydroxyindoleacetic acid were reduced to 3-10% of control levels as a result of multiple intrabrainstem injections of 5,7-dihydroxytryptamine. This treatment strongly reduced or abolished ARCA in most cases but did not reduce atropine sensitive cerebral activation which appears to be dependent on ascending cholinergic projections from the basal forebrain to the cerebral cortex. Therefore, ARCA appears to be dependent on ascending serotonergic inputs to the forebrain. PMID- 2598023 TI - Physiological properties and patterns of projection in the cortico-cortical connections from the second somatosensory cortex to the motor cortex, area 4 gamma, in the cat. AB - The physiological properties of neurons in the second somatosensory cortex (SII), and the pattern of projection of these neurons to area 4 gamma of the motor cortex in cat were studied by using single unit recording and collision techniques. Antidromically activated neurons were recorded along the anterior and posterior regions of the lateral bank of the anterior suprasylvian sulcus (ASSS) and from the middle part of the anterior ectosylvian gyrus (AESG) following weak intracortical microstimulation (ICMS) to area 4 gamma. Stimulation of the region around the activated neurons failed to produce muscle contraction or movement with currents of 30 microA or less. The majority of antidromically identified neurons received somatotopically organized afferent inputs from the skin on the contralateral side of the body. A small number of SII neurons received bilateral input. In 91% of the cases receptive field information was available for both the antidromically activated SII neuron and for neurons around the stimulating electrode in area 4 gamma. In 71% of these cases, both cortical sites were activated by sensory input from the same or adjacent peripheral area of the body. Neurons in the rostrocaudal region of the lateral bank of ASSS and the upper part of AESG (forelimb area) projected to the lateral cruciate gyrus of the motor cortex (forelimb area), while neurons in the ventrocaudal region of the medial part of AESG (hindlimb area) projected to the medial part of the postcruciate subregion of the motor cortex (hindlimb area). Antidromically activated SII neurons were typically found in layer III. These results suggest a topographically organized pattern of projection to the motor cortex from SII. PMID- 2598024 TI - Kinase inhibition lengthens the period of the circadian pacemaker in the eye of Bulla gouldiana. AB - The inhibition of protein kinase activity by the isoquinoline sulfonamide, H-8, lengthens the period of the Bulla ocular circadian rhythm in a dose-dependent manner. In addition, the phosphorylation of 5 proteins is markedly affected by H 8. The observed correlation between H-8's period lengthening effects, and its effects on the phosphorylation of specific proteins, suggests that: (1) these proteins are candidate components regulating the period of the circadian rhythm; and (2) the daily changes in membrane potential underlying the circadian rhythm are mediated by similar mechanisms that serve to change neural function in other systems; modulation of protein kinases. PMID- 2598025 TI - Regional changes in brain dopamine and serotonin metabolism induced by conditioned circling in rats: effects of water deprivation, learning and individual differences in asymmetry. AB - Rats were trained, using water reinforcement, to turn in circles (rotation) during 1 h daily test sessions. After achieving criterion performance (100 full turns per hour) for at least 10 consecutive sessions, rats were sacrificed 20 min after starting a session and levels of dopamine, DOPAC (3,4-dihydroxyphenylacetic acid), serotonin, and 5-HIAA (5-hydroxyindoleacetic acid) were assayed in nigrostriatal (corpus striatum), mesolimbic (nucleus accumbens) and mesocortical (medial prefrontal cortex) brain regions. Other control groups of rats were comparably water deprived or satiated at the time of sacrifice. Although, as previously reported, evidence of 'two populations' of rats was again apparent with respect to the relationship between direction of spontaneous turning and asymmetry in striatal dopamine levels, there were no lateralized effects of operant rotational training on striatal dopamine and DOPAC levels nor on the DOPAC/dopamine ratio. There were, however, bilateral neurochemical effects of both rotational training and water deprivation in striatum: an increase in the 5 HIAA/serotonin ratio in both sexes was attributable to learning whereas an increase in the DOPAC/dopamine ratio in males was attributed to water deprivation. A bilateral decrease in the DOPAC/dopamine ratio in the mesolimbic and mesocortical regions of both sexes was also induced by water deprivation. The only lateralized neurochemical changes associated with learning to rotate in the operant task occurred in the medial prefrontal cortex: in both sexes, dopamine levels were higher in the ipsilateral than in the contralateral cortex and the DOPAC/dopamine ratio was greater in the contralateral than in the ipsilateral cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598026 TI - AF64 depletes hypothalamic high-affinity choline uptake and disrupts the circadian rhythm of locomotor activity without altering the density of nicotinic acetylcholine receptors. AB - Ethylcholine aziridinium ion (AF64) was synthesized from acetylethylcholine mustard hydrochloride and 5 nmol was infused into the third ventricle of rats. Seven days after AF64 treatment, sodium dependent high-affinity choline (HACU) uptake was decreased by 54% in the hypothalamus. The density of hypothalamic (-) [3H]nicotine binding sites and [alpha-125I]bungarotoxin sites in AF64-treated animals did not differ significantly from controls. A second experiment was performed to elucidate the effect of AF64 treatment on HACU and determine the effect of AF64 on entrained circadian rhythms. Animals were infused with artificial CSF or 5 nmol AF64. Locomotor activity and body temperature were recorded for 3 weeks before and 3 weeks after treatment. Ten of 14 AF64-treated animals showed a decrease in the ratio of dark cycle:light cycle locomotor activity. The decrease in dark-cycle activity was correlated with a disruption of a predominant circadian rhythm. The circadian rhythm (CR) of core body temperature was disrupted only transiently, but the CR of locomotor activity remained disrupted for the duration of the experiment in several AF64-treated animals. HACU was decreased by 48% in animals with disrupted rhythms in comparison with controls but was not significantly decreased in AF64-treated animals with normal dark-cycle activity and circadian activity. These data suggest that the AF64-treated animal may be a good model for studying the role of acetylcholine in maintaining the integrity of certain circadian rhythms. PMID- 2598027 TI - Neurotoxic effects of partially oxidized serotonin: tryptamine-4,5-dione. AB - Neurotoxicity of tryptamine-4,5-dione (4,5-DKT), a partially oxidized form of serotonin, was assessed after microinjection into the lateral ventricle, hippocampus, or cingulate cortex of rats followed by Fink-Heimer staining for axon terminal degeneration. Intracerebroventricular injections of 4,5-DKT resulted in terminal degeneration which was most dense in layers I and III of insular cortex, layer I of cingulate cortex, and the molecular layer of the dentate gyrus. Argyrophilic and probably degenerating neurons were most frequently subjacent to the granule cell layer of the dentate gyrus, layers II, III, and IV of entorhinal cortex, and throughout the insula. Injections of 5-20 micrograms of 4,5-DKT directly into the hippocampus indicated that toxicity was dose-dependent. These injections produced axon terminal degeneration and neuronal argyrophilia in sectors CA1 and CA3 and in the dentate gyrus. Argyrophilic neurons were also observed in layers II, III, and IV of ipsi- and contralateral entorhinal cortices. Injections into anterior and posterior cingulate cortices produced degeneration in the caudate and anterior thalamic nuclei, and contralateral cortex. These results indicate that 4,5-DKT is a novel indole neurotoxin which exhibits a striking propensity for medial limbic system structures including some of those affected in dementia of the Alzheimer type. PMID- 2598028 TI - The human torsional vestibulo-ocular reflex during rotation about an earth vertical axis. AB - Using the magnetic search coil technique, we have measured the gain and time constant (Tvor) of the torsional vestibulo-ocular reflex (VOR) in 4 subjects who were rotated about an earth-vertical axis with their necks extended and faces supine. Following a 1-min period of rotation in darkness at 50 degrees/s, the post-rotational response to a velocity off-step had a group mean gain of 0.43 and Tvor of 3.7 s. Following a 1-min period of rotation in the light at 50 degrees/s, the post-rotational response in darkness had a group mean gain of 0.29 and Tvor of 4.1 s. Following rotation in darkness with the neck flexed and head prone, the post-rotational response, measured in two subjects, had a mean gain of 0.39 and Tvor of 5.7 s. Similar results were obtained with 100 degrees/s stimuli. In all subjects, the gain and Tvor of the torsional VOR were smaller than corresponding values for their horizontal VOR; these smaller values can be related to the different visual demands made of the torsional VOR. PMID- 2598029 TI - Hemicholinium-3 prevents the working memory impairments and the cholinergic hypofunction induced by ethylcholine aziridinium ion (AF64A). AB - The present study examined whether intraventricular administration of the potent high affinity choline transport (HAChT) inhibitor hemicholinium-3 (HC-3) would attenuate the memory impairments and the neurochemical deficits induced by i.c.v. ethylcholine aziridinium ion (AF64A). Male Sprague-Dawley rats were trained to perform a delayed-non-match to sample radial arm maze (RAM) task in which a 1-h delay was imposed between the fourth and fifth arm selections. Following 30 acquisition trials, animals were bilaterally injected with AF64A (3 nmol/side) or AF64A preceded by HC-3 (20 micrograms/side) into the lateral ventricles and allowed 7 days to recover before behavioral testing resumed. Control animals received either artificial cerebrospinal fluid or HC-3. AF64A-treated rats were significantly impaired in their performance of the RAM task as evidenced by fewer correct choices following the delay and more total errors to complete the task. This behavioral deficit was associated with a significant (32%) decrease in HAChT in the hippocampus. In contrast, animals pretreated with HC-3 exhibited no significant decreases in HAChT or decrements in RAM performance. These findings indicate that the memory deficits resulting from intraventricular administration of AF64A are a consequence of the compound's cholinotoxic properties and in particular its interaction with the HAChT carrier. Furthermore they demonstrate that a select alteration of septohippocampal cholinergic activity is sufficient to disrupt working memory processes. PMID- 2598030 TI - MPTP is proconvulsant acutely but has no long-term effect in rodent models of seizure and epilepsy. AB - 1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) was used to lesion the substantia nigra of rodents to look for changes in various animal models of epilepsy and seizures. MPTP, acutely administered to C57BL/6J mice, could cause seizures at high doses and enhanced maximal electroshock seizures at lower doses. Older mice were more sensitive to MPTP toxicity. MPTP given over 1 week to produce a 75% drop of striatal dopamine had no effect on seizure thresholds to pentylenetetrazol or picrotoxin and did not change the maximal electroshock seizure. Epileptic gerbils given maximally tolerated doses of MPTP had only a slight striatal dopamine reduction (32%) while seizures remained unaltered. The data are consistent with the hypothesis that chronic dysfunction of dopamine containing substantia nigra neurons have no significant influence on seizures in these animal models. PMID- 2598031 TI - Centrally administered glucagon stimulates sympathetic nerve activity in rat. AB - The effect of pancreatic glucagon given intravenously, intracerebroventricularly and microinjected into the nucleus of the solitary tract on sympathetic activity in the cervical trunk and adrenal nerve was examined in rat. In each case glucagon caused a relatively long-lasting substantial increase in discharge of both nerves. This finding shows that glucagon can act centrally to stimulate sympathetic activity. The most probable site for the sympathoexcitatory effect of glucagon is the nucleus of the solitary tract. PMID- 2598032 TI - CGRP expression in the rat olivocerebellar system during postnatal development. AB - CGRP-like immunoreactivity was studied in the cerebellar cortex and precerebellar nuclei of neonatal rats. From postnatal day (PD) 0 to PD 13-15, CGRP immunoreactivity was transiently found in fiber-like structures around Purkinje cells, defining parasagittal bands. Following the same time course, transient labeling was also found in the inferior olive neurons which, in the adult, distribute their axons to the olivocerebellar compartments corresponding to the immunoreactive bands. It is concluded that CGRP is transiently expressed in specific climbing fiber compartments. PMID- 2598033 TI - After-effects of moving textured background in motion-sensitive neurons of anuran optic tectum. AB - Motion-sensitive neurons in anuran optic tectum were shown to respond to a stationary object centered in the excitatory receptive field, if a textured background moved for a while and then stopped ('motion after-response'). This motion after-response was attributed to a post-inhibitory rebound activation derived from effects of masking the excitatory receptive field center surrounded by an antagonistic inhibitory region. It was suggested that a similar rebound activation mechanism may also be involved in a certain type of perceptual motion after-effects in humans. PMID- 2598034 TI - Prefrontal cortex gating of auditory transmission in humans. AB - Middle-latency auditory evoked potentials (MAEPs) were recorded in controls and patients with focal lesions in dorsolateral prefrontal cortex. Unilateral prefrontal lesions increased the amplitude of the Pa component of the MAEP beginning at 25-35 ms poststimulus. The data suggest that prefrontal cortex exerts early inhibitory modulation of input to primary auditory cortex in humans. PMID- 2598035 TI - Anti-goldfish glial fibrillary acidic protein (GFAP) recognises astrocytes from rat CNS. AB - A polyclonal antibody to goldfish GFAP recognises, immunohistochemically, astrocyte populations in rat brain, spinal cord and optic nerve. The pattern of staining compares favourably with that obtained using a polyclonal anti-human GFAP or a monoclonal anti-porcine GFAP. These results are consistent with the notion that GFAP is well conserved in vertebrate phylogeny. PMID- 2598036 TI - Correlative decrease of large neurons in the neostriatum and basal nucleus of Meynert in Alzheimer's disease. AB - A quantitative investigation was performed on the large neurons in the neostriatum and basal nucleus of Meynert (bnM) in patients with Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). The degree of decrease of the large neurons in the neostriatum was quite similar to that in the bnM; these decreases were significantly correlative in AD, but not in PSP. These findings indicate that the large neurons in the neostriatum and bnM, which are considered to be cholinergic and to exclusively possess nerve growth factor receptors in the cerebrum, degenerate simultaneously in an equal ratio in AD. PMID- 2598037 TI - The activity pattern of phrenic motoneurons during the aspiration reflex: an intracellular study. AB - Membrane potential trajectories and discharge characteristics were measured intracellularly in 29 phrenic motoneurons of anesthesized, paralyzed and artificially ventilated cats during hypercapnic respiration and the aspiration reflex. Fifteen 'active' cells discharged spontaneously during inspiration, and the remaining 14 'quiescent' cells exhibited no discharge in spite of strong central respiratory drive. The mean membrane potential of the quiescent cells during inspiration (-62 +/- 4 mV) was significantly lower than the threshold level determined for the active cells -52 +/- 4 mV). The mean axonal conduction velocity was slower for the active (60.4 +/- 8.7 m/s) than quiescent cells (67.4 +/- 6.9 m/s). All phrenic motoneurons discharged during the aspiration reflex with maximum instantaneous frequencies ranging from 6 to 357 Hz. No differences were found for the maximum discharge frequency during the reflex between the active and quiescent cells. Although there were differences in the slopes of the depolarization during inspiration between the groups of cells, no such difference existed in the slopes during the aspiration reflex. The threshold level for the first spike during the reflex was the same as that during inspiration but the level for successive spikes became progressively less negative while spike amplitude decreased and duration increased. Stimulation of the nasopharynx to elicit the aspiration reflex was found to alter the timing of the subsequent respiratory cycles. PMID- 2598038 TI - Electron-lucent degenerating geniculate terminals in cat striate cortex. AB - Degenerating geniculate axon terminals in cat striate cortex have been previously described as electron-dense. After electrolytic lesion of the lateral geniculate nucleus, we observed degenerating terminals in layer 4 of striate cortex which were electron-lucent. The lucent terminals --which co-exist with the dense terminals--are characterized by a pale matrix, large size, distorted mitochondria, and a paucity of synaptic vesicles. They preferentially (82.5%) contact dendritic spines. Lucent terminals were common in layer 4, rare in layer 6, and absent from layers 1 through 3 and layer 5. This distribution is consistent with the projection of the lateral geniculate nucleus to the striate cortex. Thus, geniculate terminals undergo both the electron-lucent and electron dense degeneration reactions in cat striate cortex, and the lucent terminals make a significant contribution to the amount of degeneration present. The relationship of lucent degeneration to other forms of degeneration is discussed. PMID- 2598039 TI - Carbachol phase shifts the circadian rhythm of locomotor activity in the Djungarian hamster. AB - The effects of light on the circadian system may involve the neurotransmitter acetylcholine (ACh). The purpose of the present study was to determine whether carbachol, a cholinergic agonist, mimics the phase-shifting effects of light on the circadian rhythm of locomotor activity (CRLA) in the Djungarian hamster. Phase response curves (PRCs) were measured for blind animals injected intracerebroventricularly with either vehicle or carbachol at different circadian times. Carbachol produced significant phase delays in the CRLA when administered at circadian time (CT) 12-16 and small, but significant phase advances when given at CT 8. No consistent phase shifts were observed in response to carbachol injections at other circadian times. Phase shifts produced by carbachol injections at CT 8 and 12 were similar for both sighted and blind animals. Light pulses to sighted hamsters produced phase advances at CT 20 and phase delays at CT 12. Both the carbachol PRC and the PRC for light pulses in the Djungarian hamster have phase delay regions in the early subjective night. However, these two PRCs have different phase advance regions. These results indicate that carbachol mimics some of the effects of light on the circadian system in the Djungarian hamster and support the hypothesis that cholinergic mechanisms may play a role in mediating some of the phase-shifting effects of light on the circadian clock of mammals. PMID- 2598040 TI - Decreases in excitatory synaptic transmission and increases in recurrent inhibition in the rat dentate gyrus after transient cerebral ischemia. AB - Excitatory transmission along the perforant path from the entorhinal cortex to the granule cells of the dentate gyrus was evaluated two days after 10 min of transient cerebral ischemia in the rat. The amplitude of the population spike, and the amplitude and the initial slope of the population excitatory postsynaptic potential (EPSP) evoked by the perforant path stimulation were measured across a range of stimulus intensities, and were compared with control values. Inhibitory interactions were evaluated using the paradigm of paired pulse stimulation, comparing the amplitude of the population spike evoked by the second pulse of a pair to the initial spike. The maximal values of the initial slope of the population EPSP and the population spike were reduced in the ischemic group. Also, the extent of paired pulse inhibition was greater in the ischemic group. These results suggest that: (1) excitatory synaptic transmission along the perforant path is impaired in the postischemic period, (2) inhibition of the dentate granule cells is enhanced in this period. These results are not consistent with the hypothesis that there is a hyperactivation of the tri synaptic circuit in the chronic postischemic period that accounts for the excitotoxic death of CA1 neurons. PMID- 2598041 TI - The protease inhibitor leupeptin interferes with the development of LTP in hippocampal slices. AB - The effect of leupeptin, an inhibitor of thiol-proteases, was tested on the induction of long-term potentiation (LTP) in field CA1 of hippocampal slices. Two h of drug application did not produce substantial changes while a greater than 3 h application caused a sizeable reduction in the degree of LTP induced. Leupeptin had no obvious effects on the facilitation of postsynaptic responses occurring within or between the short high frequency bursts used to induce LTP, suggesting that the drug acted on cellular chemistries occurring after the initial physiological events that normally trigger LTP. These results are consistent with the hypothesis that a calcium-activated thiol protease (calpain) is involved in the induction of LTP. PMID- 2598042 TI - Morris water task impairment and hypoactivity following cysteamine-induced reductions of somatostatin-like immunoreactivity. AB - The effects of cysteamine-induced reductions of somatostatin-like immunoreactivity (SLI) on spatial learning, passive avoidance, and locomotor activity were examined in adult Sprague-Dawley rats. Cysteamine hydrochloride (100 mg/kg, s.c.) produced 54% and 50% reductions in SLI in cortex and hippocampus, respectively, and impaired escape latencies and spatial probe behavior in the Morris water task. Although cysteamine-treated rats displayed hypoactivity in the activity boxes, their swim speed in the Morris water task was unaffected. Cysteamine did not impair passive avoidance retention when administered immediately following training or prior to daily retention testing. These results suggest a role for somatostatin in spatially-mediated behaviors in rats. PMID- 2598043 TI - Effects of drinking and central angiotensin II stimulation on organ blood flow in conscious rats. AB - While the hemodynamic response pattern accompanying feeding behavior has been well characterized, there is less information about the hemodynamic changes associated with drinking. In the present study, we have measured organ blood flows in conscious, unrestrained rats during schedule-induced drinking behavior, using the tracer microsphere technique (diameter of spheres 15 +/- 3 microns; labels: 141Ce, 113Sn). In addition, we determined the hemodynamic response pattern following intracerebroventricular (i.c.v.) injection of 100 ng angiotensin II (ANG II) (a dose known to be dipsogenic) in rats that were not allowed to drink during the experiment. The hemodynamic responses during drinking behavior included (a) significant increases in blood flow through the kidney, stomach and small intestine, (b) a decrease in blood flow through skeletal muscle, and (c) no significant changes in the rest of the organs. ANG II i.c.v. elicited (a) significant decreases in blood flow through the kidney, stomach, small intestine and skin, (b) a significant increase in blood flow through the liver (hepatic artery), and (c) no significant changes in blood flow through the brain, heart, lung (bronchial arteries), colon, skeletal muscle (biceps) and testis. We conclude that spontaneous drinking behavior in rats is associated with a characteristic hemodynamic drinking response, which resembles a classical feeding reaction. In non-drinking rats the hemodynamic response pattern following ANG II i.c.v. was different from the drinking response, providing further evidence, that the behavioral and cardiovascular effects of the neuropeptide can be dissociated. PMID- 2598044 TI - Light microscopic and ultrastructural localization of GABA-like immunoreactive input to retrogradely labeled sympathetic preganglionic neurons. AB - The organization of gamma-aminobutyric acid-like immunoreactive (GABA-LIR) processes was studied within the sympathetic preganglionic neuropil of male Sprague-Dawley rats and pigeons (Columba livia). Sympathetic preganglionic neurons were retrogradely labeled following horseradish peroxidase (HRP) injections into either the adrenal medulla or superior cervical ganglion in rats or into the avian homologue of the mammalian stellate ganglion (paravertebral ganglion 14) in pigeons. GABA-LIR staining was visualized using peroxidase antiperoxidase (PAP), avidin-biotin complex (ABC), or post-embedding immunogold methods. The pigeon preganglionic neuropil contained a dense network of GABA-LIR processes with punctate swellings that encircled sympathetic preganglionic perikarya within the principal preganglionic cell column (column of Terni) and the nucleus intercalatus spinalis. GABA-LIR spinal neurons were intermingled among HRP-labeled sympathetic preganglionic neurons within the column of Terni and throughout the zona intermedia. In the rat the density of the GABA-LIR processes within the four thoracic sympathetic preganglionic nuclei was less than that observed in the pigeon. Nevertheless, GABA-LIR profiles distinctively dotted preganglionic perikarya within the nuclei intermediolateralis pars principalis and pars funicularis, nucleus intercalatus spinalis and the central autonomic nucleus. GABA-LIR neurons were rarely observed within the nucleus intermediolateralis pars principalis, but were numerous in the zona intermedia and area X. No GABA-LIR spinal neurons in either vertebrate were retrogradely labeled with HRP. The ultrastructural arrangements of GABA-LIR processes within the sympathetic preganglionic neuropils of pigeons and rats were similar. GABA LIR boutons formed symmetrical synaptic contacts and contained small round electron-lucent vesicles (50 nm) and one to several larger dense-core vesicles (80 nm). GABA-LIR terminals contacted HRP-labeled sympathetic preganglionic perikarya in all spinal nuclear regions in both vertebrates. More frequently, GABA-LIR boutons synapsed on dendrites. Occasionally, axo-axonic configurations were observed; each time only one of the axonal elements was GABA-LIR. Numerous unmyelinated and some thinly myelinated GABA-LIR axons coursed through the sympathetic preganglionic neuropils of both vertebrates. Synapses between GABA LIR processes were present within the sympathetic preganglionic neuropil of both vertebrates. GABA-LIR dendrites were contacted by unlabeled terminals (predominantly small spherical vesicles with asymmetric synaptic specializations) and GABA-LIR terminals on GABA-LIR dendrites were similar in appearance to those synapsing on sympathetic preganglionic cell bodies and dendrites. PMID- 2598046 TI - Role of the cerebellum in the ontogenesis of the equilibrium behavior in the young rat: a behavioral study. AB - Young cerebellectomized and control DA/HAN strained rats, one day to 1 month old, were submitted to an equilibrium test. Cerebellectomized animals, operated when 10-, 20- or 24-day-old, were either trained-operated-trained (trained every day before and after cerebellectomy), naive-operated-trained (cerebellectomized while naive and trained every day after the operation), or naive-operated-naive (tested at one given day after the operation). Control rats were either trained-controls (trained every day) or naive-controls (tested at a given day). Relevant comparisons show that (1) in control rats, the maturation of the equilibrium behavior does not depend on a specific training, at least to a great extent; however, training increases the rate of acquisition of the maximal score. (2) Rats cerebellectomized at day 10 and trained after cerebellectomy only are not able to learn a given motor pattern, while rats cerebellectomized by the 20th or 24th day are; however, their scores are always lower than those of control animals trained from the same age. Cerebellectomy alters the ontogenesis of the equilibrium behavior more especially as the operation is early. (3) Impairments of the equilibrium behavior after cerebellectomy can be explained by both motor disorders and learning processes deficiency. (4) Preoperative training counterbalances the effects of cerebellectomy in improving postoperative scores only when the cerebellum is removed at day 24. From these results it can be concluded that, in the rat, the cerebellum is involved in the learning processes that sustain the ontogenesis of the equilibrium behavior as it is in other motor learning mechanisms. PMID- 2598045 TI - Mechanisms of seizure suppression during rapid-eye-movement (REM) sleep in cats. AB - REM sleep is the most antiepileptic state in the sleep-wake cycle for human generalized epilepsy, yet the neural mechanism is unknown. This study verified the antiepileptic properties of REM sleep in feline generalized epilepsy and also isolated the responsible factors. Conclusions are based on 20 cats evaluated for generalized EEG and motor seizure susceptibility before and after dissociation of specific REM sleep components. Bilateral electrolytic lesions of the medial lateral pontine tegmentum created a syndrome of REM sleep without atonia. Systemic atropine created a syndrome of REM sleep without thalamocortical EEG desynchronization. Identical results were obtained in two seizure models, systemic penicillin epilepsy and electroconvulsive shock. (1) Normal REM sleep retarded the spread of EEG seizure discharges and had even more potent anticonvulsant effects. (2) Selective loss of 'sleep paralysis' (skeletal muscle atonia) during REM abolished REM sleep protection against myoclonus and convulsions without affecting generalized EEG paroxysms. (3) Conversely, selective loss of thalamocortical EEG desychronization abolished REM sleep protection against generalized EEG seizures without affecting clinical motor accompaniment. These results suggest that the descending brainstem pathways which mediate lower motor neuron inhibition also protect against generalized motor seizures during REM sleep. Protection against spread of EEG paroxysms is governed by a separate mechanism, presumably the ascending brainstem pathways mediating intense thalamocortical EEG desynchronization during REM sleep. PMID- 2598047 TI - Dietary cis-fatty acids that increase protein F1 phosphorylation enhance spatial memory. AB - Activation of protein kinase C (PKC) facilitates long-term potentiation (LTP), a model of memory, and increases its substrate protein F1 (aka GAP43) phosphorylation in direct relation to synaptic enhancement. Unsaturated fatty acids (c-FAs) which activate purified PKC, when injected into hippocampus, enhance LTP. To determine if dietary c-FAs could alter memory itself as well as brain PKC substrate (F1) metabolism, rats were maintained for 10 weeks on fatty acid diets enriched in mono-unsaturated oleic acid (OA; 20% olive oil, w/w), or a mono- and di-unsaturated mixture of oleate/linoleate (O/L; 20% corn oil), or a saturated fatty acid diet of laurate/myristate (L/M; 20% hydrogenated coconut oil). The O/L diet group was superior to the OA and L/M groups in spatial memory performance after the first two weeks of acquisition and in later achievement of criterion performance. The O/L diet had a significantly higher hippocampal protein F1 in vitro phosphorylation than in both the OA and L/M in trained and non-trained animals. Significantly, animals that made fewer errors showed higher F1 phosphorylation (r = -0.70). Diet both increases brain PKC substrate phosphorylation and enhances maze learning, confirming the feasibility of enhancing learning and memory by dietary regimens derived from basic neurochemical studies of synaptic plasticity. PMID- 2598048 TI - Autoradiographic distribution of [3H]hemicholinium-3 binding sites in human brain. AB - Since previous radioligand binding studies support the evidence that [3H]hemicholinium-3 ([3H]HC-3) selectively labels the high-affinity choline uptake (HACU) process, we have studied the autoradiographic characteristics and regional distribution of [3H]HC-3 binding to post mortem human brain tissue. [3H]HC-3 specific binding was saturable, of high affinity and exhibited an uneven distribution. High densities were observed in caudate-putamen, nucleus basalis accesorius of the amygdala, hippocampal gyrus dentatus and CA3 field, locus niger, nucleus interpeduncularis and motor trigeminal and facial nuclei. Low densities were found in areas such as neocortex, thalamus, hypothalamus or cerebellum. Our results agree with those obtained in human brain membranes and are comparable to previous autoradiographic data from rat brain. Remarkably, the distribution of [3H]HC-3 binding sites closely corresponds with that of cholinergic enzymatic presynaptic markers and HACU. These findings, together with previous data from membrane studies, allow the use of [3H]HC-3 as a selective anatomical marker of cholinergic presynaptic terminals. PMID- 2598049 TI - High metabolic activity in the dorsal vagal complex of Brattleboro rats. AB - Receptor densities for angiotensin II and atriopeptin are particularly high in the dorsal vagal complex (DVC) of the caudal medulla oblongata. Measurements of glucose metabolism in individual components of the DVC, compared with those in Long-Evans rats, revealed that the area postrema was activated selectively both in water-sated and water-deprived Brattleboro rats, which have high circulating levels of angiotensin II. Other parts of the DVC, including subnuclei of the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve, as well as brainstem structures within efferent trajectories of the DVC, had elevated rates of glucose metabolism in Brattleboro rats deprived of water overnight and in Sprague-Dawley rats dehydrated for 120 h. The findings are consistent with neural activation by angiotensin II, as either a hormone or neurotransmitter, within subregions of the dorsal medulla oblongata having high densities of putative receptors and immunoreactive perikarya and fibers containing both angiotensin II and atriopeptin. PMID- 2598050 TI - Circadian variations in local cerebral glucose utilization in freely moving rats. AB - Sokoloff's [14C]2-deoxyglucose method has been applied to investigate circadian variations in local cerebral glucose utilization (LCGU). Freely moving rats were tested during two phases of the circadian light/dark cycle. In the rats tested during darkness, elevations in LCGU, when compared with animals tested during the light period, were observed in the primary and secondary visual cortex, the primary auditory cortex, the lateral geniculate nucleus, the amygdala, the entorhinal cortex, the hippocampus, the substantia nigra and the cerebellum. A reduction in LCGU was observed in the suprachiasmatic nucleus. PMID- 2598051 TI - Convulsant peptides related to corticotropin-releasing factor (CRF). AB - Corticotropin-releasing factor (CRF) and its related peptides have some conserved primary regions. We have taken an interest in the characteristic conserved sequence, Pro-Pro-Ile-Ser, which is located in the proximal N-terminal region of the CRF family. This sequence is not included in any other biologically active peptide and protein. Biological function of this N-terminal region has not become known yet. We synthesized seventeen peptide fragments of human CRF and sauvagine which involved either this entire N-terminal sequence or part of it and determined their behavioural effect after intracerebroventricular injections to mice. Several peptides which included the Pro-Pro-Ile region as the N-terminal segment and their caused a transient convulsion dose-dependently. H-Pro-Pro-Ile OH (human CRF(4-6)) exhibited the strongest effect among these active peptides. However, these convulsant peptides did not affect the secretion of immunoreactive corticotropin in rats. PMID- 2598052 TI - Effects of intracerebroventricular infusions of naltrexone and phentolamine on central and peripheral oxytocin release and on maternal behaviour induced by vaginocervical stimulation in the ewe. AB - The effects of intracerebroventricular infusions of naltrexone and phentolamine on the ability of vaginocervical stimulation to induce maternal behaviour, and plasma and cerebrospinal fluid (CSF) levels of oxytocin, were measured in oestrogen-primed ewes. Results showed that naltrexone, but not phentolamine, significantly inhibited maternal behaviour following vaginocervical stimulation. Naltrexone also prevented the CSF increase in oxytocin following vaginocervical stimulation but was without effect on plasma levels. Phentolamine did not prevent either CSF or plasma increases in oxytocin, following vaginocervical stimulation, but reduced basal plasma levels. Results are discussed in terms of an opioid influence on maternal behaviour which may be mediated through a modulation of central oxytocin release. PMID- 2598053 TI - Preliminary observations on the physiology and pharmacology of hippocampal theta off cells. AB - The discharge patterns of phasic linear and tonic non-linear hippocampal theta off cells and the simultaneously occurring field activity [theta (theta) and large amplitude irregular activity] were studied in response to sensory input, electrical stimulation of the dorsomedial-posterior hypothalamus and systemic administration of cholinergic agents, in urethane-anesthetized rats. Sensory input, hypothalamic stimulation and the administration of eserine all produced a total reduction of the discharges of phasic linear theta-off cells when the resulting induced theta was of a frequency of 5 Hz and above. The discharges of tonic non-linear theta-off cells were also totally reduced during the same conditions, even at the lowest frequencies of induced theta. Administration of atropine SO4 abolished all theta activity previously elicited by electrical stimulation of the hypothalamus, sensory input and eserine. However, sensory input and hypothalamic stimulation still produced the reduction of discharge rates of both types of theta-off cells in the presence of atropine SO4. The linear relation between the discharge rate of phasic linear theta-off cells and levels of hypothalamic stimulation was also preserved in the presence of atropine. It was suggested that GABA may mediate the discharge properties of hippocampal theta-off cells. PMID- 2598054 TI - Selectivity of the hippocampal projection to the prelimbic area of the prefrontal cortex in the rat. AB - Afferent connections of the medial and lateral prefrontal cortex of the rat arising from the hippocampal formation were investigated using iontophoretic application of the fluorescent tracer, Fluoro-gold. Our results demonstrate that the projection which originates in the temporal part of the CA1 hippocampal field and in the prosubiculum is restricted to the prelimbic area of the prefrontal cortex. PMID- 2598055 TI - Calcium currents in a vertebrate presynaptic nerve terminal: the chick ciliary ganglion calyx. AB - Ca currents (ICa) were recorded from presynaptic nerve terminals in the chick ciliary ganglion. Ciliary neurons are innervated by a single nerve terminal that extends over a wide area of the neuron surface to form a 'calyx'. The neurons were dissociated enzymatically with the calyx intact and the patch clamp technique was used in the whole cell mode to record ion currents. A small inward ICa (peak current 20-80 pA) was recorded that was blocked by external Cd. Only one component of ICa was detected. This was recruited at positive membrane potentials, exhibited no evidence of inactivation during a 25-ms depolarizing pulse, and deactivated rapidly. Thus, the ICa recorded in this vertebrate presynaptic nerve terminal was similar to the high-voltage activated, fast deactivating, current reported in other neurons. PMID- 2598056 TI - Withdrawal-induced activation of locus coeruleus neurons in opiate-dependent rats: attenuation by lesions of the nucleus paragigantocellularis. AB - Single unit activity was recorded in the locus coeruleus (LC) of anesthetized, morphine-dependent rats during naltrexone-precipitated withdrawal. As has been reported previously, LC neurons displayed a strong withdrawal-induced activation of firing rate. Radio-frequency lesions of the nucleus paragigantocellularis (PGi), a major LC afferent, greatly attenuated withdrawal-induced activation of neurons in the LC ipsilateral but not contralateral to the PGi lesion. Lesions of the prepositus hypoglossi, another major LC afferent, did not prevent the withdrawal-induced activation of LC neurons. Kynurenic acid, a non-selective excitatory amino acid antagonist known to block PGi-induced excitations of LC neurons, also blocked the withdrawal-induced activation of LC neurons. These studies indicate that withdrawal-induced activation of the LC in opiate-dependent rats is mediated at least in part by afferents from the PGi which utilize an excitatory amino acid transmitter. PMID- 2598057 TI - D-, L- and DL-fenfluramine cause long-lasting depletions of serotonin in rat brain. AB - D-Fenfluramine (1.6-12.5 mg/kg), L-fenfluramine (1.6-25 mg/kg), and DL fenfluramine (1.6-25 mg/kg) injected s.c. twice daily for 4 consecutive days produced dose-related depletions of serotonin (5-HT) levels in somatosensory cortex, striatum, hypothalamus, and hippocampus of rats (n = 5-8/group) sacrificed two weeks after the last injection. While the results indicate that long-lasting effects of racemic fenfluramine are due to both stereoisomers, the magnitude of depletions caused by the isomers varied with dose, suggesting that they have different neurochemical effects. PMID- 2598058 TI - [Different effects of a weak static and a weak rotating magnetic field on the growth of mycobacteria]. AB - The authors studied the effect of weak static and weak rotating magnetic field of the same intensity on the growth of some slow- and some fast-growing mycobacteria and on the course of the enzymatic reaction of iron reduction by fast-growing mycobacteria. The experiments yielded the following results: 1. Weak rotating magnetic field inhibited totally the growth of all mycobacteria tested. In the weak static magnetic field the mycobacteria exhibited, after the initial phase of growth depression, full growth comparable to that in controls. 2. The enzymatic reaction of iron reduction by mycobacteria was blocked in the weak rotating magnetic field, whereas in the weak static magnetic field the final phase of this process was comparable to the results obtained in controls. PMID- 2598059 TI - [Vacuolated neurons in the superior cervical ganglion in rats after repeated stress]. AB - In the article the authors deal with unsolved problem of the occurrence and character of vacuolated neurons (VN) in autonomic ganglia. They describe their own investigations of vacuolated neurons in the superior cervical ganglion of male rat (Wistar) after repeated stress and fixation of the tissue in glutaraldehyde/OsO4. Vacuolated neurons had a well-preserved structure of ganglion cell in spite of that in cytoplasma they contain vacuoles reaching enormous size. Vacuoles had very characteristic content. They were filled in by content of thin density. Along the membrane of the vacuole were cytoplasmatic extensions, their transverse profiles and isolated invaginations of the membrane of vacuole. From the structure of the vacuole cannot be appreciated the character of the vacuole--whether it is phagosomes or the reservoir of cell metabolite established for its function. Because the vacuolated neurons have the same structure as vacuolated neurons in autonomic pelvic ganglia of the rat, the authors in discussion dealt especially with the results of the investigation of the mentioned ganglia. PMID- 2598060 TI - [A scanning electron microscopy study of the ependyma in the lateral cerebral ventricle in humans]. AB - The apical surface of ependymal cells in the cornu anterius of the lateral ventricle of the brain was studied in man. The surface of ependymal cells displays varied differentiation, the cells have microvilli, spherical processes, and cilia. In the cornu anterius ependymal cells without cilia as well as with one cilium and even several cilia were observed. Different types of cells occur in groups forming so-called ependymal areas, which are constituents of the lining of the ventricular walls. Ependymal areas with a large number of cilia were recorded along with areas without cilia and so-called transitory ependymal areas with a small number of cilia. There are no sharp borderlines between the individual areas. PMID- 2598061 TI - [Morphological correlates and heredity in functional asymmetry of the cerebral hemispheres]. AB - Morphological findings which may be associated with asymmetric functions of the hemispheres have mostly appeared over the last two decades. They concern the leftsided dominance of the temporal plane and of the cytoarchitectonic region TpT, as well as of the regions which have connections with them. The posterior horn of the left lateral ventricule is usually longer and the left occipital lobe larger. The findings are associated with the leftsided location of speech functions rather than with motor dominance. Several hypotheses have been put forward attempting to explain the mode of heredity of handedness: the hypothesis of biological left--right maturation gradient, the polygenic hypothesis, further the hypothesis suggesting that one pair of genes determines the hemisphere dominant for motor and speech functions and another pair determines whether the dominant hand will be controlled by the ipsilateral or contralateral hemisphere. The hypothesis of Annette offers a plausible explanation of the heredity of handedness. It proposes that the development of a right-handed or left-handed individual is accounted for by the presence or absence of the gene which determines the dominance of the left hemisphere for speech and facilitates the development of right-handed motor dominance. PMID- 2598063 TI - [The yield and quality of DNA extracted from blood samples stored under various conditions]. AB - The effect of different conditions of blood sample storage on the yield and quality of the extracted DNA was studied. Samples of whole umbilical blood were divided into eight groups containing 10 samples each and stored as follows: A--no storage, DNA extracted immediately; B--24 hours at 4 degrees C; C--24 hours at room temperature; D--7 days at 4 degrees C; E--3 months at -18 degrees C; F--6 months at -70 degrees C; G--14 days at -70 degrees C, the samples were thawed one time and frozen again; H--14 days at -70 degrees C, the samples were 3 times thawed and frozen. DNA was isolated and yields quantified by spectrophotometry at 260 and 280 nm. The average DNA yield in the individual groups ranged from 574.5 to 1,075 micrograms per 10 ml of whole blood. Although variations in the yield of DNA were observed both within and among groups, there were no significant changes with respect to different storage conditions. However group H yielded significantly more DNA (900 micrograms/10 ml, p less than 0.05) compared to the control group A. After digestion with restriction endonuclease and electrophoresis in agarose gel, all DNA preparations were found to be of high molecular weight and in digestible condition. The results can be used to advantage in storing DNA for purposes of molecular diagnosis of genetic diseases. PMID- 2598062 TI - [Chronic hepatitis in pregnancy]. AB - The paper deals with the course of different forms of chronic hepatitis in pregnancy, as well as with the effect of chronic hepatitis on the course of gestation and on the fetus. Suggestions are put forward as to conditions which still agree and those which disagree with pregnancy when the woman already suffers from chronic hepatitis. The procedure of immunoprophylaxis of newborns from HBsAg-positive mothers is also presented. PMID- 2598064 TI - [High-frequency modulated positive pressure in the treatment of pneumopathies in premature infants]. AB - The application of high frequency modulated continuous positive airway pressure (CPAP) into the airways by using a binasal cannula is described. High frequency oscillation of 15 Hz at amplitude depth of modulation of 15-25% of the overpressure value was modulated on the basic CPAP. The equipment used is described and some results obtained in using this therapy are presented. The frequency of spontaneous ventilation was decreased, PaO2 increased in the first hours of therapy, pH became rapidly normalized and clinical signs of respiratory distress were disappearing. The reported therapeutic method resulted in reduced mortality rate of immature infants. PMID- 2598065 TI - [The present state and role of internal medicine in Slovakia]. AB - Information on the current trends of development of internal medicine is presented. The aims of internal medicine are described in the light of the development of all branches of medicine. PMID- 2598066 TI - [Preparation of medical students and physicians teaching health education]. AB - In the sphere of health protection we witness at present the increasing role of the human factor, of the individual factor, and of its active involvement in health protection of the whole society. These facts call for intensified activities in health education, concerning particularly health workers who have to stimulate and guide the population to better health protection. To achieve this, greater attention has to be focused on methodological questions of health education as well as on intensive undergraduate and postgraduate training of physicians. The present scope, content and orientation of this training at both levels requires innovations reflecting the tasks and goals created by present-day conditions. The authors analyze some topical questions concerning the training of undergraduates and of postgraduates specially involved in health education. (Ref. 3.). PMID- 2598067 TI - [Space diet]. AB - Food prepared for astronauts meets various physical and biological requirements determined by living conditions in a space environment. Onboard systems, work programs, launch costs impose weight and volume limitations. For all investigated food items, the manufacturing technique must take into account all flight specific mechanical parameters. From a nutrition and sanitation standpoint, food packs must be designed to comply with certain specific effects of long term flights ans selected food items must be thoroughly safe, which requires very strict laboratory testing. The diet must also be varied, if possible it should match astronauts' personal preferences. Food preparations must be easy to use. Space food items are original applications of existing technologies: they are of very high quality. PMID- 2598068 TI - [Television, advertising, and nutritional behavior of children]. AB - The more and more prevalent misuse of custom of TV programs is a society's phenomenon, specially in the rich countries. This misuse is particularly dangerous for children, because of the implication of three factors: repercussion on health and familial climate, inauspicious impact of advertisings and nibling's phenomenon. Therefore, the children are manipulated, even if they keep a critical mind; in fact, they are very receptive, and by seduction-persuasion, they undergo an indoctrination according to the felt pleasure. In order to better understand the importance of this phenomenon day be day, an inquiry has been realised in school, near 509 pupils from 6 to 10 years old, in Moselle, and near they relatives, thanks to a questionnaire concerning the interdependance between TV, advertisings and nutritional behavior of children. The results demonstrate that more than 97% of children look at TV almost each day, the weekly average being about 25 hours, that's to say 2 H 40 the days with school and 5 H the free days. 75% of children practice the nibbling during the projection of programs. The power of advertising for foods is very strong: 75% of children eat them regularly. Then there is a defect of normal diet of children, under the pressure of a sure indoctrination induced by the advertisings. This is a social phenomenon capable to lead progressively to pathological consequences: obesity, cardio vascular diseases, degenerative troubles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598069 TI - [Familial testicular regression syndrome]. AB - The rare syndrome of embryonic testicular regression or agonadism with XY karyotype is described in this paper in a sibship of 7 including 3 cases of regression at a earlier time (in three amenorrheic sisters and on case of tardive and incomplete regression in a brother with bilateral testicular hypotrophy. The antigen H-Y is present in the three sisters. The pathogenesis of this syndrome, compared with that of pure gonadal dysgenesis is discussed. PMID- 2598070 TI - [Cochlear and facial nerve function after surgery of acoustic neuroma]. AB - Oto-neuro-surgical teams of Bordeaux University Hospital operated at this day, 700 acoustic neuroma. A retrospective study of the 120 last cases has shown the facial function be abnormal clinically in 16% of cases and in 50% from the electrophysiological point of view. Immediately after surgery: 39% have normal function (grade I), 22% have partial palsy (grades II, III, IV), 39% have total palsy. With 3 months follow up these percentages improve to become respectively 53%, 34% and 13%. For the cochlear function, 28 patients had good hearing before surgery (average pure tone threshold less than or equal to 35 dB and speech discrimination score greater than or equal to 70%). Results depend on the size of the tumour and on the difficulty of dissection during surgery. The hearing could be preserved at a good level in 8 patients (28.5%). PMID- 2598071 TI - [An assay for aldosterone precursors: a tool for clinical diagnosis and adrenal physiopathology]. AB - After their contribution to the study of 18 hydroxycorticosterone as an intermediate in aldosterone biosynthesis the authors present here a new series of assays for the measurement of plasma aldosterone precursors as a pertinent tool in the extensive study and clinical evaluation of the mineralocorticoid function of the adrenal. These radioimmunoassays must be undertaken under strict technical conditions: time of blood withdrawal and also posture. Their use is irrelevant in any other clinical feature but the salt loss syndrome and hyper mineralo corticism together with or without high plasma aldosterone. PMID- 2598072 TI - [Medical and nutritional aspects of vitamins]. PMID- 2598074 TI - [From poliomyelitis to myopathies: management of respiratory insufficiency in neuromuscular disease]. AB - Chronic respiratory insufficiency by neuromuscular disease is a problem with unknown fullness. Thirty eight patients were followed in a specialized center and have been treated by several means: Intermittent positive pressure breathing was employed for 6 patients with a vital capacity which was between 30 and 50% of normal values. It prevents thoracic deformation and aggravation of restrictive syndrome. It was used for preventive effect. Endotracheal ventilation by tracheostomy (13 cases) is an invasive but necessary method which was employed when there were obstructive bronchial secretions and very deep respiratory insufficiency (vital capacity under 30%). Ventilation by extra thoracic prosthesis was used in eighteen patients. Body ventilator, wrap, pneumo-belt were chosen in function of abdominothoracic morphology. "Personalized" nasal mask ventilation is a great interest non invasive method. It was applied in one case (myopathy with sleep apnea syndrome). PMID- 2598073 TI - [Iatrogenic vascular lesions]. AB - We have observed during a period of 24 years, 277 vascular iatrogenic injuries. An analytic study has revealed the prominent following etiologies; Injections, perfusions, catheterisms and arteriographies: 121 cas; Orthopedic surgery: 69 cas; General surgery: 14 cas; Surgery and sclerosis of varicose veins: 71 cas. The author analyse the various aspects of these lesions, most of them are due to imperfect technique or professional error. A special attention is given to the 82 very serious cases, seen in emergency with more of 50% of bad results. Vascular risk is not frequent, but it exist in very numerous medico-surgical procedures. Early recognition and early correction of the vascular lesions reduce the incidence and the gravity of complications. PMID- 2598075 TI - [Cancer of the colon. Survival and prognosis after surgical treatment in a series of 1000 patients]. AB - During the last 20 years, 1,000 patients were operated on for a single cancer of the colon, 497 men and 503 women (mean age: 67 years). Resection was performed in 93% of the patients and resection with curative intent in 80% of the patients. Carcinomas located on the left colon were usually treated by segmental resection. There were 8 postoperative deaths, 4 of them after curative resection. The crude 5-year survival rate established from the 754 patients operated on before 1984, with a follow up for all of them except 5, was 60% after all operations and 76% after curative resection. Prognosis was not influenced by tumor site and time elapsed between first symptom and operation. The 5-year survival rate was higher in female patients and in patients less than 50 years. Tumor staging was the main prognostic factor. Based on Dukes' classification, the 5-year survival rate for A, B, C, D tumors was 90%, 78%, 56% and 5% respectively. PMID- 2598076 TI - [Hospital and university physicians: causes of malaise]. PMID- 2598077 TI - Pitfall-to-avoid pharyngeal opacities caused by bismuth subgallate. AB - Bismuth subgallate is used occasionally as a hemostatic agent for packing the adenoidal and tonsillar beds after an adenotonsillectomy. Containing a heavy metal, it is relatively insoluble and poorly absorbed. It produces faint opacities on plain radiographs and these may mimic a foreign body or pharyngeal calcification. We report a 13-year-old girl with linear radiopacities in the nasopharynx and in the palatine tonsillar bed. Careful and complete clinical information pinpointed the exact (iatrogenic) cause of these radiodensities. PMID- 2598078 TI - Computed tomography in the diagnosis of dysplasia epiphysealis hemimelica. AB - Dysplasia epiphysealis hemimelica (Trevor-Fairbank's disease) is a rare anomaly that must be differentiated from other epiphyseal and periepiphyseal abnormalities. Computed tomography is extremely useful in diagnosing and defining the extent of this dysplasia, as well as in assisting the surgeon in planning definitive treatment. PMID- 2598080 TI - Delayed common femoral artery stenosis due to blunt trauma. AB - Arterial occlusion or stenosis due to blunt trauma is rare. Only isolated examples have been reported. The majority result from sport-related trauma or are iatrogenic in nature. The clinical importance of blunt trauma is that it can create delayed vascular stenosis but few symptoms at the time of the incident. This is even more important in children and adolescents as any delay in diagnosis can lead to severe sequelae such as limb shortening and other growth disturbances. We here report a patient with common femoral artery stenosis after a bicycle injury in whom, apparently uniquely, delayed symptoms developed after eight months. PMID- 2598079 TI - CT appearance of annular pancreas: a case report. AB - We report here the computed tomographic appearance of an annular pancreas complicated by chronic pancreatitis. PMID- 2598081 TI - "Kirlian photography" film artifacts. AB - A film artifact due to static discharges from the fingers is described. These are similar to Kirlian photographs, ostensibly representing the radiant spiritual aura. PMID- 2598082 TI - Effective dose equivalent. PMID- 2598083 TI - Modulation of SCE induction and cell proliferation by 2-mercaptoethanol in phytohemagglutinin-stimulated rat lymphocytes. AB - 2-Mercaptoethanol (2-ME) is used as a medium supplement to enhance the proliferation of lymphocytes cultured in vitro. In this study, we have examined the effects of 2-ME on cell growth and on SCE induction in cultures of unstimulated and phytohemagglutinin (PHA)-stimulated Fischer 344 rat lymphocytes. There were virtually no metaphases detected in cells cultured without PHA. In PHA stimulated cultures, 2-ME decreased SCE frequency but it enhanced SCE frequency in the presence of 5 to 12.5 microM bromodeoxyuridine (BRdU). Both mitotic and replication indices were increased in the PHA/2-ME system. The levels of incorporated exogenous thymidine, in the presence of 2-ME, were relatively low in unstimulated cells, suggesting that 2-ME is not mitogenic for T-cells. However, 2 ME enhanced PHA-induced response of T-cells as evidenced by increased levels of thymidine incorporation into cellular DNA. The growth-promoting effects and the decrease in SCE frequency caused by 2-ME upon PHA stimulation indicate that 2-ME may alter the nature of interaction between PHA and cellular activating properties or the replicative processes. PMID- 2598084 TI - Enhanced cadmium cytotoxicity in A549 cells with reduced glutathione levels is due to neither enhanced cadmium accumulation nor reduced metallothionein synthesis. AB - Glutathione (GSH) depletion sensitizes human lung carcinoma (A549-T27) cells to the cytotoxic effects of Cd++. The effects of GSH depletion on Cd++ accumulation and Cd++-induced metallothionein (MT) content were investigated to determine the possible role of these Cd++ responses in the sensitization process. Cellular GSH was depleted to 20% to 25% of control levels with buthionine sulfoximine (BSO), or diethyl maleate (DEM), respectively. Neither treatment significantly affected Cd++-induced accumulation of exogenous 35s-cysteine into intracellular MT in a dose-dependent fashion. The results indicate that neither enhanced Cd++ accumulation nor reduced MT synthesis plays a primary role in affecting enhanced Cd++ cytotoxicity in A549 cells with reduced GSH levels. Although BSO inhibition of GSH synthesis enhanced MT synthesis, it sensitized the cells to Cd++, which suggests an additive effect of GSH and MT in cadmium cytoprotection. This observation also raises the possibility that intracellular cysteine levels limit Cd++-induced MT accumulation rates. PMID- 2598085 TI - Toxic effects of 7 beta-hydroxycholesterol on rat liver primary cultures, epithelial lines and co-cultures. AB - The toxic effects of 7 beta-hydroxycholesterol (7 beta-OHC) on cultures and co cultures of rat hepatocytes, rat liver epithelial cell lines, and rat liver fibroblast lines were investigated. Hepatocytes in primary culture or co-cultured with proliferative epithelial cells, were not affected by the presence of 7 beta OHC at a concentration of 400 microM over a period of 72 hours. In contrast, proliferative cultures of liver epithelial cell lines and liver fibroblast lines were killed by 50 microM 7 beta-OHC within the first 24 hours. Established liver epithelial cells (hyperploid) were more sensitive to 7 beta-OHC than the same line at early passages (diploid). When hepatocytes and liver epithelial cells were co-cultured and treated with 100 microM 7 beta-OHC, only epithelial cells were lysed. A concentration of 50 microM 7 beta-OHC was toxic to co-cultures of liver epithelial cell and fibroblasts together. In a serum-free medium, the cytotoxic concentration of 7 beta-OHC was lower than that in the serum supplemented medium. Thus, liver epithelial cells cultured alone or co-cultured with hepatocytes were killed at 12.5 microM and 50 microM 7 beta-OHC, respectively. Finally, cholesterol concentrations four-fold that of 7 beta-OHC antagonized the lethal effects of 7 beta-OHC in the serum-free medium. PMID- 2598086 TI - The exposure of the general population to benzene. PMID- 2598089 TI - [Comparison of DNA flow cytometry and microspectrophotometry in gastric carcinoma]. AB - Flow cytometric (FCM) and microspectrophotometric (MSP) measurements of nuclear DNA content were made in 52 fresh gastric carcinoma specimens and in 30 gastric mucosal specimens from patients with chronic gastritis DNA aneuploidy was found in 60% (32/53) cases of gastric carcinoma, and it appeared more frequently in well-or moderately differentiated tubular adenocarcinoma (90%) than in undifferentiated and mucous cell carcinoma (23.6%) (P less than 0.01). No aneuploidy was found in benign gastric mucosal samples, but their proliferative cell fractions were significantly higher than those in normal control gastric mucosal samples (p less than 0.01). The comparison of the results measured with FCM and MSP showed a high correlation rate (r = 0.07, p less than 0.005). The advantages and limitations of both methods are discussed, and the authors think that the two can be regarded complementary to each other and may be used in combination for more precise cytochemical analysis. PMID- 2598088 TI - A report on methods to reduce, refine and replace animal testing in industrial toxicology laboratories. AB - The Committee to Promote Principles of Reduction, Refinement and Replacement of Animal Testing in Industrial Toxicology Laboratories was established in 1987 to work toward industrywide improvements in laboratory animal testing methods. The committee's goals are to gather information about effective nonanimal testing techniques and other methods of conserving and improving the care of laboratory animals, to work toward the systematic validation of nonanimal alternatives, and to disseminate useful information about progressive programs and policies throughout the industrial toxicology community. This is the first in a continuing series of reports the committee plans to produce as part of an ongoing program to promote communication among industrial toxicologists about successful methods of reducing, refining and replacing animal testing. Here are some of the report's major findings: (1) Animal care and use committees charged with the oversight of laboratory animal use are a universal practice at the companies surveyed. (2) Significant reductions in the number of animals used for acute toxicity testing have taken place at all the companies during the last 5- to 10-year period. (3) Structure-activity relationships (predicting a test compound's properties based on the known properties of familiar chemicals with similar structures) are widely used to minimize, but not replace, the use of animals. (4) Tissue and organ culture systems are being used with increasing frequency for screening and mechanistic studies, but are not completely replacing animal evaluations as a final step. (5) There is a pressing need for the systematic and scientifically sound validation of nonanimal alternative techniques to reduce the use of animals in toxicology testing while satisfying requirements for the protection of public safety. PMID- 2598090 TI - [Morphometric analysis and automatic diagnosis of gastric dysplasia and well differentiated adenocarcinoma]. AB - A morphometric analysis system for gastric dysplasia and well differentiated adenocarcinoma was set up by the techniques of digital image processing and the theory of mathematical morphology. For 100 cases, seven parameters were measured. A trainable statistic classifier in multidimensional space is designed on the basis of large number of samples obtained from the analysis system. And then we have set up an objective quantitative automatic diagnostic system for gastric dysplasia and well differentiated adenocarcinoma. PMID- 2598087 TI - Bovine spermatozoa as an in vitro model for studies on the cytotoxicity of chemicals: effects of chlorophenols. AB - The suitability of ejaculated bovine spermatozoa as an in vitro model for the assessment of the cytotoxic potential of chemicals was evaluated using several endpoints: swimming activity, adenine nucleotide content, membrane integrity and oxygen consumption. A series of chlorophenols inhibited sperm motion (motility and velocity) in a concentration-dependent manner. This could be determined quantitatively and reproducibly by means of videomicrography and automatic computer image analysis. The sperm immobilizing potency increased with increasing chlorination and was positively correlated with lipophilicity. Concentrations which reduced the percentage of moving sperm to 50% of controls ranged from 43 microM for pentachlorophenol (PCP) to 1440 microM for 4-monochlorophenol (4-MCP). Determinations of adenine nucleotides and percentages of viable cells revealed qualitative differences between the action of PCP and the lower chlorinated phenols. While the latter decreased the total adenine nucleotide contents and the percentage of unstained cells in parallel to motion inhibition, no such changes occurred after exposure to immobilizing concentrations of PCP. Penta-, tetra- and trichlorinated phenols stimulated cellular respiration, indicating their uncoupling activity, at concentrations lower than those necessary for motion inhibition. The results indicate that bovine spermatozoa may become a useful in vitro model for the toxicological evaluation of chemicals providing quantitative as well as qualitative data. PMID- 2598091 TI - [Magnetic resonance imaging of occult intracranial malformations]. AB - 11 patients with angiographically occult intracranial vascular malformations proved by surgery and pathology were studied by magnetic resonance imaging (MRI). The chief MRI findings were: On T1-weighted imaging, there was a homogeneous or heterogeneous hyperintensity or isointensity signal at the centre of the lesion with a surrounding rim of hypointensity signal; On T2-weighted imaging, there was a hyperintensity signal at the centre and hypointensity signal at the peripheral region. Differential diagnosis between hemorrhagic tumor and occult vascular malformation lies in that the latter has no edema and is often single. comparing with CT, the size of occult vascular malformation on MRI was equal to that on CT. PMID- 2598092 TI - [Experimental study on the antigoiter effect of high casein nutrition]. AB - In this experiment, goiter was successfully induced in rat with MMI, and the antigoiter effect of 25% and 50% casein diet was observed. The results showed that the diet with 50% casein is more effective than that with 25% casein in counteracting MMI and preventing goiter in rat. The antigoiter mechanisms of high protein nutrition might be as follows: Protecting the mechanism of thyroid iodine transportation through the follicular cell, and therefore accelerating thyroid iodine metabolism; Relieving thyroid peroxidase (TPO) from the inhibitive effect of MMI and facilitating thyroid hormone synthesis; Coordinating the function of hypothalamus-pituitary-TSH-thyroid axis and protecting the wholeness of thyroid cell and thus avoiding the occurrence of pathological changes. PMID- 2598093 TI - [Purification and some properties of platelet aggregating protein (PAP) from the plasma of a patient with thrombotic thrombocytopenic purpura]. AB - A new platelet aggregating protein (PAP) was purified from the plasma of a patient with acute thrombotic thrombocytopenic purpura (TTP) using A1 (OH)3 adsorption, PEG fractionation, DEAE cellulose chromatography, lentil lectin Sepharose 4B chromatography and gel filtration HPLC. The M. W. of this PAP was estimated to be 59,000. It induced the aggregation of washed platelets from normal subjects and the same patient after recovery. The antigenic material was present in 2 out of 6 other TTP patients but was absent in 7 normal subjects, two patients with DIC and two patients with ITP. The aggregation of washed platelets by PAP was concentration dependent and required energy metabolism, Ca2+ and fibrinogen. PAP was present in the plasma of a subset of TTP patients and was likely the cause of platelet thrombi in the microvessels in these patients. PMID- 2598094 TI - [A study on cutaneous microcirculation in the human]. AB - From the research on diseased tissues of the skin, we found that there are evidences of microcirculatory damages at the following sites: (1) Arterial limbs; (2) Venule limbs (3) All Loops (4) Top of Loops (5) Skin Papilla. On the other hand. We have observed such atypical loops, under microcirculatory microscope and recording color TV, as: (1) big fishhook-like (2) dumb-bell like (3) glomerular (4) hemorrhagic (5) vascular (6) big tadpole-like (7) net-like (8) papillar edema. For clinical diagnosis and treatment, studies on cutaneous microcirculation may prove to be helpful. PMID- 2598095 TI - [Studies on the persistence of immunity 14-15 years after vaccination with a live measles vaccine]. PMID- 2598096 TI - [Studies on the persistence of immunity 15 years after revaccination with measles vaccine]. PMID- 2598097 TI - [In vitro diagnosis of penicillin allergy by dot immunobinding assay]. PMID- 2598098 TI - [A study on the mechanism of ototoxicity of aspirin]. PMID- 2598099 TI - Allergen injection immunotherapy (hyposensitization) on trial. PMID- 2598100 TI - Comparison of a new type of skin test (Phazet) with existing skin test methods and the radioallergosorbent test (RAST). AB - A new skin test method (Phazet) for diagnosis of immediate-type allergic disease was tested in 232 patients attending the Guy's Hospital Allergy Clinic, and compared with conventional skin test methods, using Bencard and Pharmalgen allergen solutions, and with serum IgE antibody tests (RAST). Six allergens (cat, dust mite, Cladosporium, grass pollen birch pollen and plantain pollen) were used, as well as histamine and a negative control. Phazet proved easy to use and was popular with inexperienced operators (medical and dental students). For the majority of allergens there was reasonably good agreement with the different tests, but overall Phazet and RAST produced fewer positive results than the other skin tests methods. In particular, the frequency of positive histamine tests was lower with Phazet (82%) than with Bencard or Pharmalgen (99%), but this discrepancy was lower in the second part of the study when the minimum time for the insertion of the needle (1 sec) was more scrupulously observed. Phazet offers a convenient and practical alternative to conventional 'wet' skin test methods. PMID- 2598101 TI - Pigeon breeders' disease: quantitative immunoelectrophoretic studies of pigeon bloom antigen. AB - This study employed quantitative immunoelectrophoretic techniques, on sera from confirmed cases of pigeon breeders' disease (PBD), to investigate the antigenicity of a pigeon bloom extract, implicated as a sensitizing agent in this disease. On crossed immunoelectrophoresis the maximum number of antigenic components identified was 29 for the bloom compared to 10 for pigeon serum. A major component was shown to be closely related to pigeon IgA, and demonstrated partial crossreactivity to the pigeon IgG. This component also showed identity with the major component of a pigeon droppings extract, considered to be derived from intestinal IgA. Only trace amounts of serum albumin were detected and most other bloom components were not serum-related. Although greater overall antigenic similarity was found to pigeon droppings extract, at least three of the bloom components appeared to be specific. The bloom extract also contained a low amount of an alpha-techoic acid-like component, causing some non-specific reactivity. Pigeon feather dust or 'bloom', like pigeon droppings, is therefore a potent source of antigens associated with PDB--pigeon IgA being a major component of both antigens. PMID- 2598102 TI - Obstructive airways disease in non-smoking subjects with pigeon fanciers' lung. AB - The aim of the study was to assess the degree of airways involvement in non smoking subjects with extrinsic allergic alveolitis resulting from pigeon-derived antigens. Two hundred and eight pigeon fanciers completed a questionnaire of symptoms, performed spirometry on a Vitalograph Compact spirometer and had IgG antibody to pigeon gamma-globulin measured. Eighty fanciers had the acute form of pigeon fanciers' lung (PFL) and these subjects were less likely to be current smokers (P less than 0.001). Subjects with PFL had a higher prevalence of chronic bronchitis (P less than 0.001), large airways (P = 0.014) and peripheral airways obstruction (P less than 0.001). The prevalence of chronic bronchitis and peripheral airways obstruction increased significantly as the level of antibody to pigeon gamma-globulin rose. Peripheral airways obstruction, as manifest by a reduced FEF25-75%, was the most common abnormality found. Airways disease is an important feature of the acute form of PFL and consists of a hypersecretory disorder in the form of chronic bronchitis and of obstructive airways disease particularly affecting the peripheral airways. PMID- 2598103 TI - The effect of topical steroid application on natural killer cell activity. AB - Peripheral blood natural killer (NK) cell activity of a group of 10 healthy non atopic volunteers was reduced following the topical application of 15 g of 0.1% betamethasone valerate ointment to the skin nightly for 1 week. In contrast, no such effect was observed when the inactive base of the steroid ointment was used. NK cell activity dropped significantly by day 7 (P less than 0.05) and then recovered, although NK cell activity at day 22 was still lower than that observed at the start of the experiment. These findings suggest that topically applied steroid is absorbed in sufficient amounts to cause a systemic effect on NK cell function. This may have implications in a number of dermatological disorders, including atopic dermatitis, where topical steroids form the mainstay of treatment. PMID- 2598104 TI - Birth season variation in asthma and allergic rhinitis. AB - The prevalence of asthma and allergic rhinitis was analysed in relation to birth month in two cohorts of 18-year-old males born in 1953 (n = 55,393) and 1963 (n = 57,150), in schoolchildren (n = 19,814) and in children with defined specific allergies (n = 1080). Among the 18-year-olds, a marked variation with respect to birth season was only found in those born in 1963, with the highest prevalence of asthma in those born August-January and of allergic rhinitis in those born November-May. In the schoolchildren with allergic rhinitis the birth season pattern was found to be similar to that in the conscripts born in 1963. The influence of month of birth on the onset of allergic rhinitis was maximum about 6 years of age and was not seen before 2, and after 10 years of age. Obvious similarities in birth season patterns were found between the unselected populations and the children with defined pollen and animal dander allergies. The differences in birth season pattern between the two cohorts of 18-year-olds were interpreted as an effect of unidentified adjuvant factors that might have developed over a 10-year period. PMID- 2598105 TI - Diagnosis of occupational asthma. AB - Accurate diagnosis of occupational asthma takes time, enthusiasm and a particular knowledge of the work situation, as well as expertise in the use of diagnostic procedures. The prognosis of patients with occupational asthma is probably improved by removing them from the responsible agent as soon as possible after sensitization occurs. However, it is much easier to make the diagnosis while the worker is still exposed to the cause of the problem. Early referral for expert investigation is therefore important. PMID- 2598106 TI - Nursing care of a patient with a subphrenic abscess. AB - A subphrenic abscess is an abscess which forms below the diaphragm and above the transverse colon. Patients in the postoperative period following gastric, esophageal or hepatic surgery are at risk of developing a subphrenic abscess especially if they are older, if they develop a leak at an anastomosis site or if there was a high operative blood loss. Nurses who are aware of high-risk patients should increase their observations of the signs and symptoms of early subphrenic abscess. Subphrenic abscesses are often managed on the general nursing units but signs of impending respiratory failure or circulatory collapse may warrant transfer of the patient to an intensive care unit. Nursing interventions are then focused on maintaining the body systems, evaluating the effects of the medical and nursing interventions and supporting the patient and family who may be very anxious at the severity of the unanticipated complication. PMID- 2598107 TI - Triage and the law. PMID- 2598108 TI - The status of women in health care. "Ceremonial dances and window dressing". PMID- 2598109 TI - The neonatal transport team. PMID- 2598110 TI - Magnetic resonance imaging of arachnoid cysts. AB - A retrospective review of magnetic resonance imaging (MRI)-computed tomography (CT) correlation was performed in 29 patients with arachnoid cysts. Short TR, short TE spin echo (SE) pulse sequences provided the best anatomic definition whereas multiple echo long TR, TE sequences allowed comparison of the signal intensity of the cyst with that of cerebrospinal fluid (CSF). Simple arachnoid cysts were isointense while neoplastic, hemorrhagic or inflammatory cysts were hyperintense relative to CSF. The CT differential diagnosis of an arachnoid cyst (depending upon its location) may include other cystic collections such as craniopharyngioma, epidermoid, astrocytoma, and chronic subdural hematoma. However, on MRI the combination of extra-axial location, morphological features, and signal intensity matching that of CSF allows one to make the diagnosis of an uncomplicated arachnoid cyst with confidence. PMID- 2598111 TI - Histological description of tomographic images of Taenia solium cysticerci in pig brains. AB - In the computed tomography (CT) scans of five pigs with neurocysticercosis (Taenia solium), interesting lesions produced by the larvae were selected. The pigs were euthanized and the corresponding lesions in their brains identified and processed for histopathology. It was found that the hypodense areas in CT scans corresponded to vesicular larvae that are presumably viable. The hyperdense areas were either solid in nature or had formed a rim around a hypodense center and in the brain slice they were either solid granulomas or colloidal cysts with inflammatory reaction in the periphery, perivascular cuffing, and vasculitis. It was not always possible to classify larvae as meningeal or parenchymatous in the CT. PMID- 2598112 TI - Primary mediastinal endodermal sinus tumors: CT evaluation. AB - Five patients with primary mediastinal endodermal sinus tumor have been evaluated by computed tomography (CT). The tumors were all located in the anterior mediastinum. Prechemotherapy CT demonstrated large, irregularly enhancing inhomogeneous masses without fat components. Calcification was visualized in two tumors. Some parts of the pleura-lung interface were irregular in four cases. Obliteration of fat planes to pericardium and chest wall was evident in all cases, and there was infiltration of intercostal muscles in four. Postchemotherapy CT in two patients who responded to chemotherapy showed either newly developed cystic lesions or cystic change of the original mediastinal mass. The cystic masses had more regular borders, a homogeneous hypodense center, and a smooth peripheral rim of contrast-enhancing tissue. PMID- 2598113 TI - MRI of the knee in diffuse pigmented villonodular synovitis. AB - Magnetic resonance imaging (MRI) was performed on 11 patients with surgically proven pigmented villonodular synovitis (PVNS) of the knee. PVNS was diagnosed on the basis of presence of hemosiderin, joint effusion, and hyperplastic synovium without significant joint destruction. MRI provided a detailed map of the distribution of the disease within the joint, emphasizing the common occurrence of the disease behind the cruciate ligaments and in synovial cysts in the popliteal fossa. MRI aided in preoperative planning and postoperative follow-up for residual and recurrent disease. Nine additional cases of joint hemorrhage, hemophilia, desmoplastic tumors, and synovial chondromatosis were included to delineate differential diagnostic criteria. PMID- 2598115 TI - Leiomyosarcoma of the renal vein: radiologic pathologic correlation. AB - Leiomyosarcoma of the renal vein is a rare neoplasm occurring more commonly in women. On sectional imaging it is difficult to differentiate from other primary retroperitoneal tumors. Here is a case report of a right renal vein leiomyosarcoma in a 40-year-old man. The ultrasound findings are described and the magnetic resonance imaging, computed tomography, and angiographic findings are illustrated and correlated with the pathologic findings. PMID- 2598114 TI - Rhinocerebral mucormycosis: a case report with magnetic resonance imaging findings. AB - Mucormycosis is a rare fungal disease most often encountered in patients who are diabetic, immunocompromised, severely burned, or who have a history of intravenous drug abuse. Intracranial presentation includes the isolated cerebral and the more common rhinocerebral forms. The computed tomography picture in mucormycosis is well documented. The magnetic resonance (MR) findings associated with mucormycosis have not been previously described. We report a case of rhinocerebral mucormycosis in a poorly controlled diabetic man where the MR findings of cavernous sinus thrombosis and thrombosis of the cavernous portion of the internal carotid artery demonstrated progression of the patient's disease in spite of his stable clinica course. The results of the MR findings directly altered the patient's therapy, thus leading to a favorable outcome. PMID- 2598116 TI - Radiology pathology conference. PMID- 2598117 TI - Cerebral cysticercosis. PMID- 2598118 TI - Estimates of MR needs. PMID- 2598119 TI - Fish oil prevents effect of high cholesterol diet on active intestinal transport of galactose. AB - We tested the hypothesis that diets containing fish oils prevent the effects of a high cholesterol diet on the morphology and nutrient uptake of the intestine. Isocaloric semisynthetic diets were supplemented with beef tallow or fish oil containing low or high amounts of cholesterol and were fed to growing female Wistar rats for 14 days, after which the in vitro jejunal and ileal uptake of glucose, galactose, long-chain fatty acids, and cholesterol was determined. Feeding cholesterol with beef tallow was associated with a 12% decrease in the jejunal mucosal surface area. Feeding fish oil decreased jejunal mucosal surface area by 24%, as compared with the beef tallow diet, but the reduction was increased to 42% when fish oil and cholesterol were fed together. Ileal surface area was unaffected by varying the major source of dietary lipid, or by adding cholesterol. Despite the effect of fish oil on the mucosal surface area, the jejunal and ileal uptake of saturated as well as unsaturated long-chain fatty acids and cholesterol was similar in the four diet groups. Cholesterol supplementation enhanced the jejunal uptake of high concentrations of galactose only when fed with beef tallow, i.e., feeding fish oil prevented the enhancing effect of cholesterol on galactose uptake observed when beef tallow was fed. Thus, (i) a fish oil diet prevents the enhancing effect of cholesterol on jejunal active transport of galactose, an effect not explained by the reduction in jejunal mucosal surface area observed with the fish oil diet; (ii) these dietary manipulations result in a clear dissociation of the morphological from the transport adaptation of the intestine; and (iii) substitution of fish oil for beef tallow as the major source of lipid in the diet prevents the influence of cholesterol on the active intestinal transport of galactose. PMID- 2598121 TI - Exercise inhibits progressive growth of the Morris hepatoma 7777 in male and female rats. AB - Male and female rats were either trained to swim for a 6-week period or they remained sedentary. Rats were implanted with Morris hepatoma 7777 after 3 weeks of swimming and were sacrificed after a further 3 weeks. Exercised rats of both sexes showed a significant reduction in tumour weight at sacrifice, compared with sedentary controls (p less than 0.01). Similarly, when rats were first implanted with tumours and then placed on an exercise program of 3 weeks duration, tumour growth was also reduced (p less than 0.05). These results suggest that the tumour may be sensitive to exercise at more than one point in its development. Tumour growth was inhibited to a similar extent whether the total swimming time was 10, 20, or 30 h over the 3-week period. Although sedentary, tumour-bearing rats were anorexic; both male and female rats showed significant improvement of appetite during the period of tumour growth, in response to exercise. Tumour implantation was associated with significant losses of whole body and muscle protein. The progression of this wasting was not significantly altered by exercise. PMID- 2598120 TI - Studies of the innervation of rabbit myometrium and cervix. AB - We characterized the innervation of isolated circular and longitudinal-oriented muscle strips from the nulliparous rabbit uterus and cervix by field stimulation (FS). FS with increasing frequency (2.5-50 pps) and voltage (2.5-70 V) caused graded increases in isometric contraction with no relaxation or inhibition of spontaneous activity. Tetrodotoxin (TTX, 3.1 X 10(-6) M) significantly reduced the FS response by 75% in all strips at higher stimulus frequencies. Contractile responses to FS were also significantly inhibited by atropine (3.5 X 10(-6) M) in circular uterus and in longitudinal cervix. Guanethidine (5 X 10(-6) M) reduced the response in all strips, as did phentolamine (3.6 X 10(-6) M) in longitudinal uterus and circular cervix. Propranolol (3.9 X 10(-6) M) did not significantly change the response in longitudinal uterus or circular cervix. In longitudinal uterus, combined guanethidine and atropine produced significant inhibition, but not statistically different from either drug alone. Similar results were seen in circular uterus. Electron microscopy and glyoxylic acid histofluorescence indicate that both blood vessels and smooth muscle in rabbit uterus are supplied with adrenergic nerves. The results suggest the presence of TTX-sensitive adrenergic and cholinergic excitatory innervation of rabbit uterus and cervix. PMID- 2598122 TI - Effects of age on the anisotropy of the descending human thoracic aorta determined by uniaxial tensile testing and digestion by NaOH under load. AB - Strips of human thoracic aortic wall taken at autopsy from 23 individuals aged 15 81 years have been tested in two ways: in uniaxial loading and by digestion in 0.1 M NaOH at 75 degrees C under a load of 50 g. The circumferentially oriented strips were more extensible in loading and took a longer time to fail while being digested under load than the longitudinal strips from the same location. The stress versus strain curve was fitted to an exponential equation of the form, stress = A[exp(B strain)]. For circumferentially oriented strips from 19 subjects, parameter A was independent of age. Parameter B increased by a factor of 2.75 from 19 to 81 years. For longitudinally oriented strips for 14 subjects, A was also independent of age and B increased by 2.4 times from 25 to 81. With digestion under load for 11 matched pairs of strips aged from 32 to 75 the circumferential strips failed in 117 +/- 23 min (standard error), while the longitudinal ones failed in 20.3 +/- 3.2 min (standard error) (p less than 0.003). The results have important implications for vessel attachments to the aorta in heart transplantation and in vascular surgery. PMID- 2598123 TI - Comparison of the effects of botulinum toxin in adult and neonatal rats: neuromuscular blockade and toxicity. AB - A single dose of botulinum toxin (BoTX) was injected subcutaneously to induce neuromuscular blockade in the triceps surae muscles of the hindlimbs of neonatal and adult rats. The efficacy of the toxin in producing complete neuromuscular blockade of the lower limb muscles, assessed by blockade of (a) postural and flexor reflexes and (b) muscle contraction in response to nerve stimulation, was dose dependent at all ages over a BoTX dose range of 10-60 ng/kg. However, BoTX was dramatically more toxic in adult animals resulting in a decline in body weight and lethal consequences in 25% of adult animals 1 week after administration of BoTX doses as low as 40 ng/kg. In contrast, neonatal animals, given the same dosage, continued to grow and no mortalities were observed. The differences in toxicity of BoTX in adult and neonatal rats are readily accounted for by the short duration of effect in the younger animals, which, in turn, is probably the result of more rapid generation of new and functional nerve terminals. PMID- 2598124 TI - Functional and electrophysiological effects of quinacrine on the response of ventricular tissues to hypoxia and reoxygenation. AB - This study examined the effects of quinacrine on the functional and electrophysiological responses of isolated guinea pig hearts and isolated canine papillary muscle and Purkinje fibre preparations. A dose-response relationship for quinacrine (0.01-10.0 micrograms/mL) was studied in isolated guinea pig hearts perfused for 40 min. Quinacrine was found to exert a concentration dependent negative inotropic effect (1.0 and 10 micrograms/mL); in the presence of the 10 micrograms/mL of the drug, hearts developed contracture, atrioventricular conduction block, and ventricular asystole. In hearts exposed to hypoxia, lactate acidosis, and glucose deprivation and then reoxygenated for 30 min, pretreatment with quinacrine (0.1 microgram/mL) for 15 min prior to the initiation of hypoxia resulted in enhanced recovery of contractile function. Administration of the drug at any other time of the hypoxia-reoxygenation protocol was without effect. However, quinacrine reduced both the incidence and duration of reoxygenation arrhythmias. To examine the possible mechanistic basis for this antiarrhythmic action, isolated canine preparations were exposed to the same conditions and then reoxygenated. Quinacrine (1 microgram/mL) significantly reduced the reoxygenation-associated loss in membrane potential and prevented inexcitability and depolarization-induced automaticity in Purkinje fibres. These results suggest that quinacrine exerts an antiarrhythmic action during reoxygenation and may do so by modifying some potential mechanisms of arrhythmia that occur in the specialized conduction system. PMID- 2598125 TI - Acute hypothyroidism slows the rate of left ventricular diastolic relaxation. AB - The effect of acute thyroid hormone deficiency on left ventricular diastolic filling was studied by radionuclide ventriculography with simultaneous right heart catheterization in nine athyreotic patients without cardiovascular disease. The patients were studied when they were hypothyroid and when they were euthyroid on replacement therapy. Peak filling rate and the time to peak filling were used to characterize diastolic function. The time to peak filling was defined as the interval from end-systole on the radionuclide time-volume curve to the time of occurrence of peak filling. The peak filling rate was determined in absolute terms from the normalized radionuclide peak filling rate and from the end diastolic volume, which was derived from the radionuclide ejection fraction and from the thermodilution stroke volume. In all patients, the values for peak filling rate were lower in the hypothyroid than in the euthyroid state (287 +/- 91 mL/s vs. 400 +/- 118 mL/s, delta = 41 +/- 13%, p less than 0.01). Peak filling always occurred during the first half of the diastolic interval. The time to peak filling was not significantly affected by the thyroid state (170 +/- 10 ms vs. 159 +/- 21 ms, delta = 7 +/- 10%). Left ventricular filling pressure as reflected by the pulmonary capillary wedge pressure and end-systolic volume were similar in both thyroid states (6 +/- 2 mmHg vs. 8 +/- 2 mmHg (1 mmHg = 133.32 Pa) and 32 +/ 11 mL vs. 32 +/- 7 mL, respectively). The data suggest that the rate of active diastolic relaxation is decreased in short-duration hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598126 TI - Comparison of the effects of several endotoxin preparations on body temperature and metabolic rate in the rat. AB - The effects of several bacterial endotoxins on body temperature and resting oxygen consumption (VO2) were compared in normal rats. Low doses (0.05 mg/kg, i.m.) of 0127:B8 phenol-extracted endotoxin caused significant increases in both parameters. Maximal febrile responses (+1.6 degrees C) occurred at a dose of 0.05 mg/kg, but higher doses produced smaller effects. The maximal increase in VO2 (17%) occurred at doses of 0.5-1.0 mg/kg. A TCA extract of the same strain of endotoxin elicited a similar pattern of responses but was less potent than the phenol extract, whereas another endotoxin 026:B6 (TCA extract) was much less potent. The data illustrate the importance of constructing dose-response curves when comparing different endotoxins and indicate that in the rat, oxygen consumption provides a useful index of the response to pyrogens. PMID- 2598127 TI - Maintenance of hepatic arterial blood flow during hemorrhage is mediated by adenosine. AB - The effect of hemorrhage (1.91 mL/min, 10 mL/kg) on splanchnic blood flow was determined in cats anesthetized with pentobarbital. The hepatic artery (HA) is relatively protected during hemorrhage and does not constrict, whereas the superior mesenteric artery (SMA) undergoes significant vasoconstriction. Adenosine receptor antagonism with 8-phenyltheophylline blocks the dilator response to infused adenosine selectively (does not block responses to isoproterenol). The dilator response to reduced portal blood flow (the HA buffer response) is also antagonized and adenosine receptor blockade converts the HA response to hemorrhage to one similar to that of the SMA. Thus, the protective dilation of the HA during hemorrhage is mediated by adenosine. In contrast, the vasodilation of the HA seen with reinfusion of the shed blood is not altered by adenosine receptor antagonism. PMID- 2598128 TI - Effects of hyperbaric oxygen in circulatory shock induced by splanchnic artery occlusion and reperfusion in rats. AB - We studied the effects of hyperbaric oxygen in a severe model of circulatory shock induced by occlusion and reperfusion of major splanchnic arteries (splanchnic artery occlusion (SAO) shock). Pentobarbital-anesthetized rats subjected to total occlusion of the superior mesenteric and the celiac arteries for 40 min developed a severe shock state, resulting in a uniformly fatal outcome after release of the occlusion. Exposure to hyperbaric oxygen at 2 ATA (atmosphere absolute) (1 ATA = 0.1 MPa) was initiated immediately after reperfusion. SAO shock rats exposed to hyperbaric oxygen maintained mean arterial blood pressure at significantly higher values throughout the postreperfusion period compared with untreated SAO shock rats (p less than 0.01), with final mean arterial blood pressures of 88 +/- 9 and 51 +/- 4 mmHg, respectively. Treatment with hyperbaric oxygen attenuated the increase in plasma activities of the lysosomal hydrolase cathepsin D (p less than 0.05), and diminished the increase of hematocrit (p less than 0.01 from untreated shock rats). Splanchnic occlusion shock rats treated with hyperbaric oxygen also exhibited a significantly higher survival rate than the untreated shock group (77 vs. 0%, respectively; p less than 0.01). Our results suggest that the beneficial effects of exposure to hyperbaric oxygen immediately after reperfusion of the splanchnic region outweigh its possible deleterious effect. PMID- 2598129 TI - Core threshold temperatures for sweating. AB - To detect shifts in the threshold core temperature (Tc) for sweating caused by particular nonthermal stresses, it is necessary to stabilize or standardize all other environmental and physiological variables which cause such shifts. It is, however, difficult to cause progressive changes in Tc without also causing changes in skin temperature (Tsk). This study compares the technique of body warming by immersion in water at 40 degrees C, and subsequent body cooling in water at 28 degrees C, to determine the core threshold for sweating, with one by which Tc was raised by cycling exercise in air at 20 degrees C, and then lowered by immersion in water at 28 degrees C. The first of these procedures involved considerable shifts in Tsk upon immersion in water at 40 degrees C, and again upon transfer to water at 28 degrees C; the second procedure caused only small changes in Tsk. The onset of sweating at a lower esophageal temperature (Tes) during immersion in water at 40 degrees C (36.9 +/- 0.1 degrees C) than during exercise (37.4 +/- 0.3 degree C) is attributed to the high Tsk since Tes was then unchanged. Likewise, the rapid decline in the sweat rate during immersion at 28 degrees C had the same time course to extinction after the pretreatments. This related more to the Tsk, which was common, than to the levels or rates of change of Tes, which both differed between techniques. Tes fell most rapidly, and thus sweating was extinguished at a lower Tes, following 40 degrees C immersion than following exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598130 TI - The effect of adrenal denervation on the metabolic effects of hyperammonemia in sheep. AB - The metabolic effect of intravenous infusion of ammonium chloride (60 mumol/(kg body weight.min] was compared in five sheep before and after adrenal denervation. Adrenal denervation completely abolished the hyperglycemic effect of ammonium chloride, diminished the rise of pyruvate and lactate concentration, and failed to influence the lipolytic effect of NH4Cl. It is suggested that the metabolic effects of ammonia are in a different degree related to the action of ammonia on the central nervous system and (i) the hyperammonemic effect of ammonia completely depends on the neurogenic increase of adrenal medullary hormones; (ii) the rise of blood lactate and pyruvate level observed during hyperammonemia is only partially mediated by adrenaline; and (iii) the lipolytic effect of ammonia ion does not depend on the nerve-controlled secretion of adrenal medullary hormones. PMID- 2598131 TI - Functional studies of nerve projections in the canine intestine. AB - An in vivo model has been developed to study nerve connections in the canine intestine, using spread of field stimulated contractions recorded proximally and distally with strain gauges and local intra-arterial injections of drugs. Excitation spread orally for several centimetres, more effectively at lower frequencies of field stimulation. This excitation was blocked by local hexamethonium or by a combination of atropine and naloxone (each of which reduced the contractions). Distal excitation occurred after a longer delay than oral excitation; during the delay there was frequently an initial relaxation response. Distal excitation was greater at higher frequencies of field stimulation, but like oral excitation it was blocked by hexamethonium or by a combination of atropine and naloxone. Distal relaxation responses were unaffected by atropine or naloxone, but were abolished by hexamethonium. "Off" contractions, those that followed cessation of field stimulation, occurred at higher frequencies of field stimulation proximally and distally near the site of field stimulation and were blocked by atropine but not by naloxone or hexamethonium. The effects of all agents given locally extended beyond the sites of injection. These results suggest that a chain of cholinergic nerves with nicotinic synapses transmit excitation orally and distally to circular muscle; these effects seem to be facilitated proximally and distally by opioid nerves and to be inhibited initially distally by a noncholinergic mechanism. Explanations of these findings are proposed. PMID- 2598132 TI - Positive hemodynamic interaction between amrinone and diltiazem in anesthetized dogs. AB - The direct negative inotropic actions of calcium channel blockers limit the use of these otherwise effective systemic and coronary vasodilators in patients with heart failure. We studied the effects of amrinone pretreatment on the dose- hemodynamic response curve of diltiazem in order to test the hypothesis that amrinone might potentiate diltiazem's positive effects in anesthetized dogs. The control group (no pretreatment, n = 6) had a typical dose-related response to diltiazem (50, 100, and 150 micrograms/kg): coronary and systemic vasodilation, increased stroke volume, and no change in myocardial work and power. Amrinone pretreatment of the study group (n = 7) altered the hemodynamic response, thus maximal systemic vasodilation and stroke volume increase at a lower diltiazem dose, a 15 to 35% increase in myocardial work and power, and more profound coronary vasodilation. We propose that amrinone, by inhibiting phosphodiesterase, potentiates diltiazem vasodilation and reflexly secreted catecholamines' actions on the heart. This positive interaction may permit effective use of lower doses of diltiazem, thus circumventing its dose-limiting direct negative effects while still profitting from beneficial peripheral, reflex, and coronary actions. PMID- 2598133 TI - Effects of subfornical organ stimulation on respiration in the anesthetized rat. AB - The studies reported here have demonstrated that electrical stimulation in the subfornical organ of the urethane-anesthetized rat elicits augmented breaths in over 90% of animals tested. Similar stimulation in immediately adjacent anatomical regions such as the hippocampal commissure was without effect. Detailed analysis of respiratory timing revealed no other significant respiratory effects of such subfornical stimulation. PMID- 2598134 TI - Frontiers in cocaine research. Symposium of the Canadian Federation of Biological Societies. Quebec, Quebec, Canada, June 15, 1988. Proceedings. PMID- 2598135 TI - The pharmacology of L-670,596, a potent and selective thromboxane/prostaglandin endoperoxide receptor antagonist. AB - L-670,596 ((-)6,8-difluoro-9-rho-methylsulfonyl benzyl-1,2,3,4- tetrahydrocarbazol-1-yl-acetic acid) has been shown to be a potent receptor antagonist as evidenced by the inhibition of the binding of 125I-labeled PTA-OH to human platelets (IC50, 5.5 x 10(-9) M), inhibition of U-44069 induced aggregation of human platelet rich plasma (IC50, 1.1 x 10(-7) M), and competitive inhibition of contractions of the guinea pig tracheal chain induced by U-44069 (pA2,9.0). The compound was also active in vivo as shown by inhibition of arachidonic acid and U-44069 induced bronchoconstriction in the guinea pig (ED50 values, 0.04 and 0.03 mg/kg i.v., respectively), U44069 induced renal vasoconstriction in the pig (ED50, 0.02 mg/kg i.v.), and inhibition of ex vivo aggregation of rhesus monkey platelets to U-44069 (active 1-5 mg/kg p.o.). The selectivity of the compound was indicated by the failure to inhibit, first, ADP induced human or primate platelet aggregation and, second, bronchoconstriction in the guinea pig in vivo and contraction of the guinea pig tracheal chain in vitro to a variety of agonists. It is concluded that L-670,596 is a potent, selective, orally active thromboxane A2/prostaglandin endoperoxide receptor antagonist. PMID- 2598136 TI - Effect of fatty acid composition of dietary fat on energy balance and expenditure in hamsters. AB - The comparative effects of feeding diets containing corn, olive, coconut, or menhaden fish oil on efficiency of energy deposition and on short term energy expenditure were examined in growing hamsters. Diets comprising oils mixed with laboratory diets at 10% oil w/w were fed ad libitum for 3 weeks. Animals fed laboratory diets were used as controls. Body composition was determined before and after the feeding period using 3H2O distribution space. Oxygen consumption was measured in each animal during the final week. Weight gains of groups fed corn and olive oil diets exceeded those of the group fed laboratory diet alone (p less than 0.05), although metabolizable energy intakes were similar across groups. Corn oil fed animals demonstrated higher carcass energy gains as fat compared with laboratory diet fed or menhaden oil fed groups. This was reflected in an increased fractional deposition of metabolizable energy intake in the group fed corn oil diet compared with the latter two groups. Fecal energy losses were lower in the group fed corn oil diet, and higher in the group fed laboratory diet alone, compared with other groups. Oxygen consumption did not differ between groups. These findings indicate that feeding dietary fish oil, compared with corn oil, favours energy substrate oxidation reducing the fraction of metabolizable energy partitioned for storage. PMID- 2598137 TI - Effects of endogenous calcium transport inhibitor from heart muscle on the active calcium uptake and passive calcium release properties of sarcoplasmic reticulum. AB - In the present study, the effects of the cytosolic Ca2+ transport inhibitor on ATP-dependent Ca2+ uptake by, and unidirectional passive Ca2+ release from, sarcoplasmic reticulum enriched membrane vesicles were examined in parallel experiments to determine whether inhibitor-mediated enhancement in Ca2+ efflux contributes to inhibition of net Ca2+ uptake. When assays were performed at pH 6.8 in the presence of oxalate, low concentrations (less than 100 micrograms/mL) of the inhibitor caused substantial inhibition of Ca2+ uptake by SR (28-50%). At this pH, low concentrations of the inhibitor did not cause enhancement of passive Ca2+ release from actively Ca2+-loaded sarcoplasmic reticulum. Under these conditions, high concentrations (greater than 100 micrograms/mL) of the inhibitor caused stimulation of passive Ca2+ release but to a much lesser extent when compared with the extent of inhibition of active Ca2+ uptake (i.e., twofold greater inhibition of Ca2+ uptake than stimulation of Ca2+ release). When Ca2+ uptake and release assays were carried out at pH 7.4, the Ca2+ release promoting action of the inhibitor became more pronounced, such that the magnitude of enhancement in Ca2+ release at varying concentrations of the inhibitor (20-200 micrograms/mL) was not markedly different from the magnitude of inhibition of Ca2+ uptake. In the absence of oxalate in the assay medium, inhibition of Ca2+ uptake was observed at alkaline but not acidic pH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598138 TI - Kidney transplants. PMID- 2598139 TI - Feminism and the future of nursing. PMID- 2598141 TI - Continuous passive motion, an innovative concept enhancing the healing process of bone fractures. PMID- 2598140 TI - Patient positioning ... (a ready-reference guide). PMID- 2598142 TI - Preventing UTI following fractured hip surgery. PMID- 2598143 TI - Arthroscopic surgery of the wrist. PMID- 2598144 TI - Tracking the AIDS virus. PMID- 2598145 TI - Health education for the elderly. PMID- 2598146 TI - Want to fight for a patient's rights? The battle may end up in court. PMID- 2598147 TI - Bone and joint transplantation. PMID- 2598149 TI - Stay sane: don't triangulate. PMID- 2598148 TI - The neuro crisis team. PMID- 2598150 TI - The human face of AIDS. PMID- 2598151 TI - Nursing education in Australia. PMID- 2598152 TI - [Masks of violence]. AB - The issue of violence against the institutionalized elderly is examined. Based on her work experience, the author describes common manifestations of violence, discusses possible causes and suggests interventions. Research into the dynamics between caregiver and resident is one such intervention. But more important, the author calls for an immediate overview of the problem. PMID- 2598153 TI - [Repetitive screams]. AB - Nurses are challenged by the repetitive shouting of the cognitively-impaired elderly. The author reflects on the known causes of this behavior and how it affects staff members. She suggests nursing actions to discourage shouting and encourages nurses to explore new ways to cope. One way is to modify staff behavior by correcting attitudes that stereotype the elderly. PMID- 2598154 TI - Radio-opaque liposomes for the improved visualisation of focal liver disease by computerized tomography. AB - Liposomes laden with radio-opaque agents (ROA) were prepared by the reverse phase evaporation method. The liposome solutions--containing 1.7-2.5 mg iodine per mg lipid--were injected into Wistar rats. 60 min post injection the rats were scanned in a Siemens CT scanner. Following the injection of 260 mg encapsulated iodine per kg bodyweight--less than half the iodine of the normal ROA bolus injection--there was a long lasting arise in liver enhancement of 40 Hounsfield units (HU). In animals with liver tumours induced by nitrosamine lesions of 2-3 mm in diameter could be detected. PMID- 2598155 TI - Gadolinium-enhanced MR imaging in the management of a midline cerebral dysgerminoma. AB - Magnetic Resonance (MR) imaging has proved to be an excellent modality for the evaluation of CNS tumors and detection of metastatic seeding through CNS pathways. We present a case of cerebral dysgerminoma in which the use of gadopentetate dimeglumine (Gd-DTPA) enhancement added important information in lesion detection and delineation for treatment planning. Our results, and a review of recent literature, suggest that Gd-DTPA-enhanced MR imaging may be useful for initial and follow-up evaluation of CNS dysgerminomas. PMID- 2598156 TI - MR compatible winged infusion set. AB - Winged infusion sets are useful for short term venous infusion in a variety of applications and may be used without problem during CT scanning, ultrasound, or most other medical imaging applications. Drawbacks of using these standard winged infusion sets during MR scanning are torque and imaging artifacts. We describe a new MR compatible infusion set that overcomes these problems. PMID- 2598157 TI - Spontaneous free perforation of the ileum in Crohn disease: CT demonstration. AB - A case of spontaneous free perforation of the ileum in Crohn disease is presented. This rare complication was demonstrated by computed tomography (CT) before becoming evident on plain films. PMID- 2598158 TI - Inverted Meckel's diverticulum. AB - Although Meckel's diverticulum is a relatively common anomaly, inverted Meckel's diverticulum has been reported rarely. We describe a 59-year-old woman with inverted Meckel's diverticulum located at the distal ileum simulating a benign tumor. Computed tomography showed a small mass with a central area of low fat density, and appearance not described previously. PMID- 2598159 TI - Parosteal lipoma of the finger: preoperative evaluation with computed tomography. AB - Lipomas are very common benign soft tissue neoplasms arising from fatty tissue and may occur anywhere in the body. They are usually slow growing, painless masses often noted in the extremities of adult women. Occurrence in the hands and feet is unusual and those found in the digits are extremely rare. We describe a case of a lipoma presenting as a soft tissue mass of the index finger and show how computed tomography was extremely helpful in preoperative assessment by accurately defining the size of the lesion, the degree of bone involvement, and even giving indication of its underlying pathology. PMID- 2598160 TI - Primary medullary hemorrhage. AB - Two patients developed primary medullary hemorrhages. Both patients were normotensive. They were both receiving oral anticoagulation but the coagulation studies were not excessively prolonged at the time that the hemorrhage occurred. The diagnosis of primary medullary hemorrhage was established by CT findings. Both patients showed CT resolution of the hemorrhage and this correlated with good clinical outcome. PMID- 2598161 TI - Correlation of computed tomography and postmortem findings of a diffuse astrocytoma: a case report. AB - Diffusely infiltrating astrocytomas often present diagnostic difficulties. We herein correlate the radiologic and postmortem findings of a diffuse astrocytoma and conclude that recognition of abnormal bilateral and fairly symmetric enlargement and increased density of normal structures in CT scans may lead to an antemortem diagnosis of the tumor. PMID- 2598162 TI - Cytogenetic and molecular changes in chronic B-cell leukemia. AB - Cytogenetic studies using B-cell mitogens indicate that approximately 50% of patients with chronic B-cell leukemia (CLL) have chromosome abnormalities. The most common abnormality is an additional chromosome 12, either as the sole abnormality or in conjunction with other abnormalities such as 14q+, 6q-, and 11q . In two instances, the 14q+ is a result of a translocation from either chromosome 11, t(11;14), or chromosome 19, t(14;19). These two translocations led to the identification of the bcl-1 and bcl-3 genes located on chromosomes 11 and 19, respectively. Very few instances of oncogene activation have been described and it does not seem to be an important mechanism in the pathogenesis of CLL. Further cytogenetic and molecular studies may provide clues for the identification of the genes involved in CLL. PMID- 2598163 TI - Abnormalities of chromosome 1 in relation to human malignant diseases. AB - Chromosome 1 is known to often be involved in various malignant diseases. Its numerical and structural aberrations have been observed in chronic and acute leukemias and solid tumors as well. Recently five protooncogenes have been assigned to the long and short arms of chromosome 1. The frequent and nonspecific occurrence of chromosome 1 rearrangements in human tumors suggests that they play an important role in the pathogenesis and progression of these diseases. The frequency, types, and time of the occurrence of chromosome 1 aberrations and their relation to the stage of the disease were studied in 317 patients with various malignant diseases. In ten patients nonrandom aberrations of chromosome 1 were observed. Two patients had CML, two PRV followed by ANLL, and the remaining six patients suffered from ANLL, ALL, Burkitt lymphoma, MF, SMMoL, and IRSA, respectively. In six patients, total or partial trisomy of the long arm or of the whole chromosome 1 was present, and in three cases balanced translocations involving chromosome 1 could be found. In the cells of one patient a duplication of the centromeric heterochromatin was seen. We analyzed the breakpoints involved. Finally, the aberrations of chromosome 1 were almost always be observed at the terminal stage of the diseases. PMID- 2598164 TI - Molecular analysis of Philadelphia-negative myeloproliferative syndromes with i(17q). AB - We report two cases of myeloproliferative syndromes in which the only karyotypic abnormality was an isochromosome of the long arm of chromosome 17. Because i(17q) is a nonrandom structural aberration found in nearly 12% of cases of Philadelphia (Ph)-positive chronic myelogenous leukemia (CML), we carried out a molecular analysis of the breakpoint cluster region (bcr) to verify the presence of genomic rearrangements characteristic of CML. The interest of the study was strengthened by the fact that i(17q) is frequently seen in CML and by recent reports showing that genomic changes of c-abl and bcr genes can be present even in the absence of a Ph chromosome. One of the two patients showed the presence of a rearranged fragment within the bcr, suggesting a Ph-positive CML diagnosis. PMID- 2598165 TI - Four cases of acute leukemia with trisomy 4. AB - We report further on four cases of trisomy 4 in acute leukemia. Two cases were FAB type M4, one was type M1, and one was an undifferentiated leukemia. Two of our patients were children, aged 13 months and 11 years, respectively. In one case there was evidence of trisomy 4 occurring as a secondary change. PMID- 2598166 TI - Ultraviolet-induced chromosomal instability in cultured fibroblasts of heterozygote carriers for xeroderma pigmentosum. AB - Fibroblast cultures of seven patients with xeroderma pigmentosum (XP), 19 healthy sibs or parents of XP patients (XP-heterozygotes), and 24 healthy normal controls were studied for chromosome instability induced by ultraviolet rays (UV). We used a UV source that contained predominantly UV-A and UV-B at an intensity of 500 J/m2 and evaluated the induction of micronuclei (MN) and sister chromatid exchange (SCE). the XP homozygotes had a UV sensitivity that was clearly above that of all heterozygotes and normal controls. Heterozygotes had an increased rate of UV-induced MN (4.76 +/- 1.96 vs. 1.82 +/- 2.05, p less than 0.0001) and increased UV induction of SCE (13.21 +/- 3.49 vs. 9.01 +/- 1.25, p less than 0.001), as compared to normal controls. These data support epidemiologic findings that suggest that XP heterozygotes are particularly cancer prone. In addition, the determination of the UV sensitivity in vitro as described may be used for genetic counseling of asymptomatic relatives of XP patients. PMID- 2598167 TI - Cytogenetic and clinical investigations in 76 cases with therapy-related leukemia and myelodysplastic syndrome. AB - Clinical, cytomorphologic, and cytogenetic investigations were carried out in a series of 76 secondary MDS and ANLL. Chromosome abnormalities were more frequent in patients with a history of multiple myeloma or macroglobulinemia (92%) and myeloproliferative disorders (82%) than in patients with previous breast cancer (40%). The secondary hematologic malignancies were mostly a trilineage bone marrow disorder. The most commonly found cytogenetic anomaly was monosomy 7, followed by total or partial loss of chromosome 5. In addition six other chromosomes, i.e., chromosome 3, 8, 9, 12, 17, and 21 seemed to be consistently involved in the pathogenetic mechanisms of secondary leukemia and MDS. PMID- 2598168 TI - Translocation t(13;17)(q12-14;p12-13) in two patients with lymphocytic lymphoma. AB - Cytogenetic studies were performed at the time of diagnosis on two patients with diffuse small cell lymphocytic lymphoma. Both patients had a similar simple karyotype with a t(13;17)(q12-14;p12-13). These observations confirm the nonrandom involvement of band 13q13 in chronic lymphoproliferative diseases. PMID- 2598169 TI - A clonal t(9;12)(q32;q21) in cultured fibroblasts from a case of Bowen's disease. PMID- 2598170 TI - A new high-yield continuous cell-culture system for lymphokine-activated killer cells. AB - We performed basic studies on a new high-yield culture system (concentrate rotary tissue-culture system) for application to adoptive immunotherapy with lymphokine activated killer (LAK) cells. Using this system, we demonstrated that up to 2 x 10(7) peripheral blood mononuclear cells/ml could be cultured in interleukin-2 with a sufficient recovery rate and cytotoxicity in short-term cultures (6 days). This system can also be used to proliferate LAK cells to four times the initial cell number with sufficient cytotoxicity for 14 days of culture. Thus, this system allows activation of sufficient numbers of cells to conduct clinical trials on humans. PMID- 2598171 TI - Pharmacokinetic studies of radiolabelled rat monoclonal antibodies recognising syngeneic sarcoma antigens. II. Effect of host age and immune status. AB - In the preceding paper it was suggested that the tumour localisation of 125I labelled syngeneic rat monoclonal antibodies (mAbs) may be limited in immunocompetent hosts by the presence of competing endogenous serum antibodies. In syngeneic congenitally athymic (nu/nu) and cyclosporin-A-treated rats (both of which fail to mount immune responses to tumour antigens) increased uptake of mAbs in tumour tissue was obtained compared with that in immunocompetent animals. However, in the case of IgG2b and IgG1 mAbs, this appeared to be due primarily to enhanced "non-specific" localisation mediated by Fc binding, since it was abolished by the use of F(ab')2 fragments with two out of three mAbs tested. Normal tissue distribution was also influenced by host immune status: in nu/nu rats the uptake of IgG2b mAbs in the spleen was up to fivefold higher than that previously found in normal animals and the levels in liver were also increased. This effect was not seen in cyclosporin-A-treated hosts, suggesting that the reticuloendothelial system of congenitally athymic animals contains cells with enhanced IgG2b-FcR activity. This hypothesis was strengthened by the observation that splenic uptake was reduced by either the use of F(ab')2 fragments, or prior "blockade" of Fc receptors by "cold competition" with excess unlabelled IgG2b mAbs. This blockade could not be effected by mAbs of any other isotype or by IgG2b F(ab')2 fragments. The former manoeuvre resulted in higher tumour specificity ratios but usually at the expense of reduced levels of tumour associated radiolabelled mAb. The latter was found to increase "absolute" tumour localisation by up to 35%. In an attempt to characterise further and compare the Fc receptor activity of intratumour and intrasplenic host cells. The distribution of IgG2b mAbs was assayed in 3-week, 8-week and 12-week-old rats. We were able operationally to distinguish the activity of these two categories of cells, suggesting that they represent either different lineages or differentially activated subpopulations: the splenic IgG2b binding was fully expressed in weanling nu/nu rats whereas the FcR activity of cells infiltrating MC24 sarcoma was limited in 3-week-old compared with 8-12-week-old hosts. A further difference was apparent in the subclass "preference" of FcR binding: in immunodeprived rats both IgG1 and IgG2b mAbs were able to bind to tumour-infiltrating host cells, but uptake of IgG1 mAbs in the spleen was always low and not reduced further by the use of F(ab')2 fragments.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2598172 TI - Initial immunochemical characterization of specific macrophage-arming factor. AB - This paper describes the initial immunochemical characterization of specific macrophage-arming factor (SMAF). SMAF is an antigen-specific factor that is released by (sensitized) T lymphocytes after contact with the specific antigen. It renders macrophages specifically cytotoxic. The specificity is dependent on the tumor-mouse combination. In allogeneic systems the specificity is H-2 directed, whereas in the syngeneic systems the specificity is tumor-specific. SMAF has a molecular mass of 65-85 kDa (established by gel filtration). By affinity chromatography SMAF could not be adsorbed with anti-(kappa + lambda light chain) immunoglobulins or anti-IgG from SMAF-containing supernatants. SMAF could be adsorbed with the monoclonal antibody 14-30 (directed against specific T cell factors), and could be eluted from columns containing the latter. Furthermore, SMAF could also be adsorbed with and eluted from affinity chromatography columns to which specific tumor cell membranes or KCl extracts of these tumor cell membranes were coupled. Other tumor cell membranes could not adsorb SMAF. Together these data show that SMAF is not an antibody but a T-cell factor with an antigen-specific recognition site. PMID- 2598173 TI - Production of specific macrophage-arming factor precedes cytotoxic T lymphocyte activity in vivo during tumor rejection. AB - Recently we published a hypothesis on the immunological events occurring during tumor rejection. One of the implications of this hypothesis is that specific macrophage-arming factor (SMAF) is produced early during the initiation of the immune response, whereas the "classical" cell-mediated immune response components, such as cytotoxic T lymphocytes (CTL), are produced later, that is, during the amplifier-effector phase. In this paper we establish the kinetics of the induction of (a) lymphocytes producing SMAF and (b) CTL. Groups of DBA/2 mice were injected i.p. once, twice or three times with irradiated and/or non irradiated syngeneic SL2 tumor cells, the injections being given at intervals of 10 days. After each of these injections the production of SMAF and the expression of CTL activity were established. The results showed that in the peritoneal cavity SMAF-producing lymphocytes appeared earlier than cytotoxic lymphocytes (CTL). In addition, it was shown (a) that SMAF does not interfere with the in vitro cytotoxicity expressed by CTL and (b) that in addition to CTL memory cells, SMAF-producing memory cells were also induced after injection of syngeneic tumor cells. These data support the hypothesis that SMAF is involved in the early phase of the cellular immune response against tumors, whereas CTL are induced later. PMID- 2598174 TI - Biological characterization of a chimeric mouse-human IgM antibody directed against the 17-1A antigen. AB - A chimeric antibody was constructed in which the murine H- and L-chain variable regions of mAb 17-1A, raised against human colorectal cancer cells, were joined with the human constant mu and kappa regions. Transfection of these constructs into the murine myeloma Sp2/0 resulted in the expression and secretion of a pentameric Ig, designated chimeric 17-1A IgM. The chimeric 17-1A IgM was subsequently compared to a previously described chimeric 17-1A IgG1 for biological activities. Both chimeric mAbs were equally effective (weight basis) in competing against the binding of murine 125I-17-1A to cultures of HT-29 colon carcinoma cells. The calculated association constants for the chimeric 17-1A IgM and IgG1 were 1.63 x 10(8) l/mol and 3.41 x 10(7) l/mol, respectively. Unlike chimeric 17-1A IgG1, the chimeric 17-1A IgM was able to render colon carcinoma target cells susceptible to lysis by both xenogeneic (rabbit) and human complement. The extent of complement-mediated lysis dependent upon chimeric 17-1A IgM was correlated to 17-1A antigen expression on target cells. HT-29 colon carcinoma cells treated with chimeric 17-1A IgM did not directly result in antibody-dependent cellular cytotoxicity by human peripheral blood monocytes. However, chimeric 17-1A IgM greatly enhanced the deposition of C3 on complement treated HT-29 cells, and concomitant incubation with monocytes resulted in heightened lysis of the tumor cells. The feasibility of enhancing host defense against gastrointestinal malignancies by the administration of this chimeric 17 1A IgM may have certain clinical advantages. PMID- 2598175 TI - Pharmacokinetic studies of radiolabelled rat monoclonal antibodies recognising syngeneic sarcoma antigens. I. Comparison of IgG subclasses. AB - The object of our current investigations is to explore the potential of antibodies for localisation and treatment of disseminated disease, using as a model rat monoclonal antibodies (mAbs) raised against syngeneic tumour-specific antigens. As part of this study, antibodies of differing isotypes with specificity for either HSN or MC24 sarcoma were labelled with 125iodine and injected intravenously into normal rats or those bearing paired tumours in contralateral flanks. The blood clearance rates of the radiolabelled antibodies were found to be influenced by immunoglobulin subclass (IgG2b greater than IgG2a greater than IgG1) and to be increased non-specifically by the presence of growing tumours. The tumour and normal tissue distributions of the antibodies tested were also found to vary according to their apparent degree of interaction with host Fc-receptor-bearing cells, to the extent that tumour specificity in vitro was not necessarily reflected in selectivity of localisation in vivo. Three IgG2b monoclonal antibodies showed preferential uptake in the spleens of syngeneic rats and non-specific accumulation in tumours. This effect was not observed with antibodies of IgG2a or IgG1 subclass, and was abolished by the use of IgG2b F(ab')2 preparations. In spite of the use of immunoglobulin fragments, varying the assay time and testing tumours of different sizes, specific tumour localisation was low with all seven monoclonal antibodies tested. The maximum uptake achieved was less than 1% of the injected dose of antibody per gram of tumour. Much higher levels of antibody localisation have been reported for human tumour xenografts growing in nude mice, but these are rarely achieved in other systems. We propose that the use of autologous monoclonal antibodies recognising tumour-associated antigens of relatively low epitope density in syngeneic hosts provides a valid alternative model in which to investigate the factors limiting more effective, specific immunolocalisation of malignant disease. PMID- 2598177 TI - Effects of CKS-17, a synthetic retroviral envelope peptide, on cell-mediated immunity in vivo: immunosuppression, immunogenicity, and relation to immunosuppressive tumor products. AB - CKS-17 is a heptadecapeptide corresponding to a region highly conserved in retroviral transmembrane proteins such as p15E. Because a relationship had previously been determined between p15E and immunosuppressive tumor cell products, we examined the effect of CKS-17, control peptides and conjugates thereof on the expression of cell-mediated immunity (delayed-type hypersensitivity, DTH) in mice. Conjugates of CKS-17 inhibited DTH reactions to sheep erythrocytes in the feet of mice. The degree of inhibition was dose dependent. Unconjugated CKS-17 had almost no effect, and control peptide conjugates had no inhibitory effect. Immunization of mice with CKS-17 conjugates, but not with control conjugates, rendered them resistant to the depression of DTH reactions, not only by CKS-17 conjugates, but also by products of cultured tumor cells. CKS-17 conjugates, but not control conjugates, also depressed the cellular inflammatory reactions induced in mouse footpads by concanavalin A (ConA) and immunized mice against the depression of ConA reactions by products of cultured tumor cells. Injections of globulin from sera of mice immunized with CKS-17 conjugates conferred upon normal recipients resistance to the depression of footpad reactions to ConA by products of cultured tumor cells. Globulin from sera of normal mice or control immunized mice did not confer such resistance. Thus conjugates of a synthetic peptide not only mimic the immunosuppressive effects of tumor products in vivo, but can also immunize mice against those effects. PMID- 2598176 TI - Non-cytotoxic asialo-GM1-positive cells exert antimetastatic activity. AB - Metastasis can be inhibited by asialo-GM1-positive spleen cells, and in this paper we show that there are two such spleen cell populations. One population is adherent and non-cytotoxic to YAC cells, whereas the other population is non adherent and cytotoxic to YAC cells. Both cell populations exert an antimetastatic activity in cyclophosphamide-treated mice that are inoculated with LL2 Lewis lung carcinoma cells. We conclude that the antimetastatic activity is not only exerted by cytotoxic asialo-GM1-positive cells (apparently natural killer cells), but also by adherent, non-cytotoxic asialo-GM1+, Thy1.2-, IgG- cells. This means that the latter exert their antimetastatic activity by a non cytotoxic mechanism. PMID- 2598178 TI - THF-gamma 2, a thymic hormone, increases immunocompetence and survival in 5 fluorouracil-treated mice bearing MOPC-315 plasmacytoma. AB - The effect of the thymic hormone, THF-gamma 2, on the immunocompetence of 5 fluorouracil (5-FU)-treated BALB/c mice, bearing MOPC-315 tumor, was examined. Treatment of noninoculated or tumor-bearing mice with THF-gamma 2 after 5-FU injection, resulted in an increase in the antibody response to sheep red blood cells and in the allogeneic response in spleen cell cultures and had no effect on the concanavalin-A-induced interleukin-2 secretion beyond that caused by 5-FU alone. Treatment with either 5-FU alone or 5-FU and THF-gamma 2 resulted in restoration to normal values of Lyt1- and L3T4-positive populations in tumor bearing mice. THF-gamma 2 prolonged the survival time of mice bearing MOPC-315 tumor beyond that observed in mice treated with 5-FU alone. PMID- 2598179 TI - Effect of virus-modified tumor cell extracts, autologous mononuclear cell infusions and interleukin-2 on oncolytic activity of effector cells of patients with advanced ovarian cancer. AB - We studied the biological responses of six ovarian cancer patients after intraperitoneal (i.p.) injections of virus-modified tumor cell extracts (VMTE) and autologous peripheral blood mononuclear cells, collected by leukapheresis after two injections of VMTE. VMTE was prepared from allogeneic ovarian cell lines, OV2774 and CaOV3, modified by influenza virus, A/PR8/34. A dose of 9 mg VMTE was given i.p. in total of 2-4 injections, and (1-9) x 10(8) autologous mononuclear cells were infused i.p., 24 h after the second VMTE injection, and 24 h and 72 h after the third VMTE injection. Both peripheral blood (PB) and peritoneal cavity (PC) effector cell cytotoxicity was significantly enhanced against the K562 cell line in the majority of patients, 24-48 h after the second and third VMTE injections. This was accompanied by a dramatic influx of neutrophils into PC (57-550-fold), increase in absolute numbers of lymphocytes, (including large granular lymphocytes) and monocytes, and resulted also in a significant decrease in the number of ascitic tumor cells (98% reduction). The infusion of autologous mononuclear cells did not appear to influence either cytotoxicity or cell infiltration of the peritoneal cavity. We also investigated the in vitro effect of recombinant interleukin-2 (IL-2) on effector cells from PB and PC from patients before and after VMTE treatment. Cytotoxicity of both of these compartments was significantly potentiated after culture with IL-2. In three out of five VMTE-treated patients, PC cytotoxicity was significantly higher after activation with IL-2 than that of patients before VMTE treatment. These data suggest that VMTE induces regional cellular immunity, which could be further potentiated by culture of PC effector cells with IL-2. Thus, combination of VMTE and IL-2 after regional administration could represent the effective therapy for patients with advanced ovarian cancer. PMID- 2598181 TI - Intravesical treatment of bladder cancer with recombinant human interferon-beta. Intravesical GKT-beta Chemotherapy Research Group. AB - In order to examine its clinical efficacy, recombinant human interferon-beta (rIFN-beta) was instilled intravesically into 51 patients with superficial bladder cancer. Ten patients, who received intermittent intravesical instillation at a dose of (3-36) x 10(6) U rIFN-beta on days 1-3 every week, showed no response. Thirty-two patients received intravesical instillation at a dose of (3 36) x 10(6) U every day for 10-20 days. Eight patients showed partial response, indicating an efficacy rate of 25%. Nine patients received divided doses of 18 x 10(6) U twice a day every day for 10-20 days. Six patients showed partial response, indicating an efficacy rate of 67%. This value was significantly higher than that obtained by administering divided doses. The response to intravesical instillation therapy with rIFN-beta varies with treatment protocol. Frequent and longer exposure to rIFN-beta may induce better regression of superficial bladder cancer. Six incidences of side-effects were found in five cases (9.8%): pollakiuria in one, pain on micturition in two, fever in two, and eruption in one case. All of these side-effects were slight and reversible after drug withdrawal. Laboratory tests showed only a few changes with low severity. Thus, rIFN-beta is potentially a new drug for instillation therapy of superficial bladder cancer, in view of the absence of adverse effects. PMID- 2598180 TI - Therapeutic efficacy of human recombinant interleukin-2 (TGP-3) alone or in combination with cyclophosphamide and immunocompetent cells in allogeneic, semi syngeneic, and syngeneic murine tumors. AB - The potential for a recombinant human interleukin-2 (rIL-2, TGP-3) alone, in combination with cyclophosphamide, and in combination with cyclophosphamide and normal immunocompetent cells to manifest biological activity in vivo was tested using allogeneic, semi-syngeneic, and syngeneic tumor-host systems in mice. The biological activity of rIL-2 was evaluated by the inhibition of the growth of tumors and the inhibition of metastases in short-term assays and, in long-term assays, the prolongation of the survival time of mice bearing subcutaneously (s.c.) or intradermally transplanted tumors. rIL-2 was injected s.c. daily continuously for up to 40 days or intermittently two to four times into mice bearing established tumors. In the short-term assays, the dose and schedule dependence of activity of rIL-2 alone was significantly manifested against sarcoma 180 in ICR mice (allogeneic) by the regression of the tumor, and was confirmed against Meth-A fibrosarcoma in BALB/c mice (syngeneic) by retarding the growth of the tumor. When assessed using these tumor, it was found that the antitumor activity of rIL-2 was schedule-dependent: the growth of tumors was more significantly suppressed when rIL-2 was injected every day for 10 days, starting on the 7th day after tumor transplantation, than when rIL-2 was injected five times every other day or twice every 5th day, even if the total amounts of rIL-2 injected were same. The continuous injection for 10 days was considered to be a standard regimen and the daily effective doses of rIL-2 were 5, 10, and 25 micrograms/mouse. Using the standard regimen and the effective doses, the activity of rIL-2 alone was also observed against two other syngeneic tumors: Colon carcinoma 26 in BALB/c mice, by retarding the growth of the tumor, and Lewis lung carcinoma in C57BL/6 mice by reducing the formation of lung metastases. When assessed using M5076 reticulum cell sarcoma, in a long-term assay, the activity of rIL-2 alone was not manifested in C57BL/6 mice (syngeneic) even when rIL-2 was injected for a long period (20 days) but it was observed in BDF1 (semi-syngeneic) mice. On the other hand, it was found that rIL-2 was effective in combination with cyclophosphamide in prolonging the survival time of C57BL/6 mice bearing the tumor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2598183 TI - Immunomodulatory effects of systemic low-dose recombinant interleukin-2 and lymphokine-activated killer cells in humans. AB - The adoptive immunotherapy of human cancer using lymphokine-activated killer (LAK) cells in combination with high-dose systemic recombinant interleukin-2 (rIL 2) has been associated with global changes in several hematological and immunological parameters while imposing profound toxicity on patients. We have evaluated an alternative LAK cell therapy utilizing low-dose systemic rIL-2 is also characterized by significant changes in immunological and hematological parameters, which are qualitatively similar to those induced by high-dose rIL-2. Low-dose systemic rIL-2, given by i.v. bolus, is cleared to baseline levels within 240 min of administration. The induction of lymphocytosis and eosinophilia, which has characterized other protocols, is also a feature of this protocol. In addition, low-dose systemic rIL-2/LAK cell immunotherapy results in increased peripheral blood mononuclear cell (PBMC) expression of T-cell activation markers such as OKIa, OKT10 and IL-2 receptor. PBMC sampled approximately 100 h after the final infusion of LAK cells demonstrated a statistically significant increase in their ability to kill natural killer (NK) sensitive and NK-resistant cell lines such as K562 and Daudi compared to baseline values (P less than .05). These data suggest that rIL-2-based immunotherapy using low-dose rIL-2 is capable of inducing quantitative hematological and immunological changes while (in combination with LAK cells) retaining the ability to mediate tumor regression in vivo. PMID- 2598182 TI - Studies of the mechanisms of toxicity of the administration of recombinant tumor necrosis factor alpha in normal and tumor-bearing mice. AB - Tumor-bearing mice have a greater sensitivity to the acute lethal effects of the administration of high-dose recombinant human tumor necrosis factor alpha (rhTNF alpha) compared to normal, non-tumor-bearing mice. We studied whether or not the presence of tumor per se was responsible for the enhanced rhTNF-alpha toxicity. Tumor-bearing mice underwent tumor excision or sham operation before the systemic administration of rhTNF alpha at staged times (0.5-24 h) following surgery. There was little survival difference between sham-operated tumor-bearing mice and tumor bearing mice undergoing tumor excision (at 24 h, treatment with 12 micrograms rhTNF-alpha, survival:sham-operated tumor bearers = 0/12, excised tumor-bearers = 0/12; p2 less than 0.01 compared to non-tumor-bearers). Mice without tumors receiving sham operation, had minimal toxicity (10 of 12 mice surviving). The injection of 3 ml Ringer's lactate i.p. before i.v. rhTNF-alpha therapy increased survival in tumor-bearing animals; following pretreatment with Ringer's lactate 30/42 mice survived 12 micrograms rhTNF-alpha compared to 6/42 surviving a similar rhTNF-alpha dose without hydration (P2 less than 0.001). Since the production of oxygen free-radical metabolites has been postulated to play a role in the acute toxicity of rhTNF-alpha, bismuth subnitrate was used to induce the enzyme metallothionein to act as a natural scavenger for these metabolites. Daily oral bismuth subnitrate treatments improved survival of mice with MCA-106 or MCA 102 sarcoma and of mice without tumors, with higher rhTNF-alpha doses (12-20 micrograms), without reducing the therapeutic effect of rhTNF-alpha against the weakly immunogenic MCA-106 sarcoma. These studies suggest methods for reducing the toxicity of rhTNF-alpha administration in clinical trials. PMID- 2598184 TI - Effect of indomethacin on tumor-infiltrating lymphocytes of a spontaneously developed murine mammary adenocarcinoma. AB - The effect of indomethacin on tumor-infiltrating lymphocytes (TIL) was investigated in a spontaneously developed and weakly immunogenic murine mammary adenocarcinoma (designated JC) in syngeneic immunocompetent BALB/c mice, a tumor model mimicking human disease. Unlike other chemically and virally induced tumors, the expansion of TIL was only possible with an enriched population of lymphocytes, isolated on a discontinuous density gradient then cultured in complete medium containing recombinant human interleukin-2 (rIL-2). The freshly isolated TIL exhibited no cytotoxicity against either the natural-killer sensitive YAC-1 or the natural-killer-resistant JC cells lines. After culture in rIL-2, the TIL of the JC tumor lysed both YAC-1 and JC. The cytotoxicity of the TIL reached a maximum between the 2nd and 3rd week of culture and decreased thereafter. Antibody- and complement-depletion tests revealed that the cells bearing asialo-GM1 antigen represented the major precursor cells of the cytotoxic TIL, which may explain its nonspecific cytotoxicity. Indomethacin was shown to accelerate the cell proliferation of the rIL-2-activated TIL, but only in the initial 2 weeks of culture and not in later culture. The addition of indomethacin to the rIL-2-containing medium at the beginning of culture resulted in a fast acting and long-lasting enhancement in cytotoxicity. These results provided a basis for the clinical use of indomethacin, i.e. acceleration in proliferation and augmentation in cytotoxicity. However, the addition of indomethacin at the end of the fourth week after rIL-2 culturing produced neither accelerated proliferation nor augmented cytotoxicity. This study also suggested that a prolonged administration of indomethacin may not be advantageous in clinical trials, since the long-term continuous presence of indomethacin in the culture has resulted in a negative effect on the growth of TIL. PMID- 2598185 TI - Local interleukin-2 therapy in bovine ocular squamous cell carcinoma. A pilot study. AB - Five cows bearing bovine ocular squamous cell carcinoma (BOSCC) were treated with low doses of recombinant human interleukin-2 (rhIL-2). A dose of 2500 U rhIL-2 was injected intralesionally and another 2500 U were injected into the subparotid regional lymph node once a day during a period of 5 consecutive days. This cycle of 5 days was repeated after an interval of 2 days. Total regression of the tumor was observed in three out of five animals. One cow showed tumor regression (greater than 80%) accompanied by metastases to the regional lymph node that were observed from the fifth week after the beginning of the treatment. Growth of the tumor of the fifth animal was retarded after treatment. In vitro proliferation of peripheral blood lymphocytes was investigated in two animals and tumor infiltrating lymphocytes in one animal during incubation in various rhIL-2 concentrations. Cytotoxic activity of both cell populations against P815, Yac-1 and BOSCC-derived cell lines increased during incubation with rhIL-2. Cultured BOSCC-infiltrating lymphocytes showed predominant killing of the BOSCC-derived autologous cell line after 4 weeks of culture. Preliminary phenotype analysis did not give conclusive results with respect to the types of cells responsible for killing. PMID- 2598186 TI - Tumor-induced alteration in macrophage accessory cell activity on autoreactive T cells. AB - Using a tumor-model system, differences in the accessory cell capabilities on autoreactive T cells of splenic macrophages from normal and tumor-bearing hosts (TBH) were assessed in the syngeneic mixed lymphocyte reaction. Tumor development caused a drop in autoreactivity. At 0 and 7 days of tumor growth, no drop in reactivity occurred when TBH macrophages were used as accessory cells and L3T4+ autoreactive T cells from normal mice were used as responder cells. However, by day 14, there was a 32% drop in reactivity, and by day 21 only 22% of the T cell reactivity remained when TBH macrophages were used as accessory cells. Alterations in macrophage Ia antigen during tumor growth were first investigated as the potential cause of reduced autoreactivity. Before tumor growth (day 0) 59% of the splenic macrophages were found to be Ia+. Day-7 TBH macrophages showed no difference in Ia antigen expression when compared to day 0 macrophages. However, by day 14, TBH macrophages showed a 9% decrease, and by day 21 they showed a 36% decrease in the number which were Ia+. Concomitant with the decrease in the number of Ia+ cells was a decrease in the density of Ia antigen expression on day 14 and -21 TBH macrophages. In day-14 and -21 TBH macrophages, two populations were seen that were Ia+. The first had a 10%-20% decrease in Ia antigen expression per cell while the second population had a greater than 50% drop in Ia antigen expression per cell. By titrating and mixing TBH macrophages with normal host macrophages, we assessed whether they could actively mediate suppression of autoreactive T cells. A titratable suppressive phenomenon was demonstrated using day-21 TBH macrophages. In contrast, day-7 and -14 TBH macrophages titrated with normal host macrophages had no effect on the syngeneic mixed lymphocyte reactivity. Lastly, we investigated whether the macrophage-mediated suppression was caused by increased prostaglandin secretion. Addition of indomethacin to cultures increased autoreactive T cell reactivity stimulated by normal or TBH macrophages (59% and 99% increase, respectively). Although indomethacin reduced suppression mediated by TBH macrophages, autoreactivity did not return to levels induced by untreated or indomethacin-treated cells from a normal host. Taken together, the data suggested that tumor growth modulates the function of macrophage accessory cells with autoreactive T cells in at least two ways: by decreasing Ia antigen expression and by increasing suppressor activity. PMID- 2598187 TI - Preparation and analysis of bifunctional immunoconjugates containing monoclonal antibodies OKT3 and BABR1. AB - OKT3 and BABR1 [anti-(breast tumour) antibody] were conjugated using N succinimidyl-3-(2-pyridy]dithio)propionate (SPDP). The procedure employed mild reducing conditions for SPDP-BABR1 and short conjugation incubations at 37 degrees C. The bifunctional immunoconjugates thus produced were isolated by HPLC gel filtration on a preparative TSK 3000 SW column. Both intact IgG and F(ab')2 fragments have been conjugated. The ratio of SPDP to IgG for the optimal yield of dimeric OKT3-BABR1 heteroconjugates was determined to be 2 for OKT3 and 1-2 for BABR1. The OKT3-BABR1 dimers were shown to be bifunctional heteroconjugates by polyacrylamide gel electrophoresis, isoelectric focusing, radial immunodiffusion, and flow cytometry. The binding specificities of the bifunctional heteroconjugates were identical to the specificities of both parent antibodies. PMID- 2598188 TI - HLA-DR antigen expression on melanoma metastases and the course of the disease. AB - Melanoma cells freshly isolated from regional lymph node metastases of 59 stage II malignant melanoma patients were analyzed by indirect immunofluorescence staining with monoclonal antibody TAL 1B5, detecting the HLA-DR alpha chain. The expression of HLA-A,B,C antigens, using antibody W6/32, was also investigated in 45 of these cases. There were no substantial differences in the course of the disease with respect to the percentage of positive cells. In 13 malignant melanoma patients two to four simultaneous and/or successive metastases (both locoregional and distant-subcutaneous) were analysed for HLA-DR. With simultaneous metastases (7 cases) the percentage of HLA-DR-positive cells was mostly very similar, and in no case was there more than 25% variation. As to successive metastases (9 cases) the percentage of HLA-DR-positive cells remained practically unchanged or decreased during the course of the disease. PMID- 2598189 TI - Augmentative effect of Nocardia rubra cell-wall skeleton on the induction of human lymphokine-activated killer (LAK) cells by the production of LAK cell helper factor(s). AB - Nocardia rubra cell wall skeleton (N-CWS) was found to synergistically augment lymphokine-activated killer (LAK) cell generation from human peripheral blood mononuclear cells (PBMC) in the presence of a suboptimal dose of recombinant interleukin-2 (rIL-2). N-CWS increased the number of PBMC expressing IL-2 receptor on their surfaces, and the presence of N-CWS at the early stage of the culture period was essential for the exertion of its augmentative activity on the LAK induction. The predominant phenotype of LAK precursor cells responding to N CWS and rIL-2 was CD3- CD16+. Culture supernatant from N-CWS-stimulated PBMC was found to act as a substitute for N-CWS in the induction of LAK generation in the presence of rIL-2, suggesting that these cells produced a factor capable of augmenting LAK cell induction (LAK helper factor, LHF). LHF was found to have a molecular mass of 29 kDa by gel filtration, and could also function as a killer helper factor to augment allo-antigen-specific cytotoxic T lymphocyte generation from human peripheral blood T cells as well as murine thymocytes. LHF showed no species specificity, indicating that it is different from IL-4. The enhancing activity of LHF was not neutralized with anti-TNF alpha, anti-IL-1 alpha, or anti IL-1 beta antibodies. Furthermore, no tumor necrosis factor-alpha (TNF alpha), TNF beta, IL-1 alpha, beta, IL-2, IL-5, IL-6 or interferon activity was detected in semi-purified LHF during enzyme-linked immunosorbant assay and biological assays. The present findings indicate that LHF produced from N-CWS-stimulated PBMC is a molecule distinct from TNF alpha, TNF beta, interferon, IL-1, -2, -4, 5, and -6, and suggest that LHF might be a novel lymphokine involved in LAK generation. PMID- 2598190 TI - The inhibitory effect of human interferon alpha on the generation of lymphokine activated killer activity. AB - The generation of lymphokine-activated killer (LAK) activity and the proliferative response to human recombinant interleukin-2 (IL-2) were significantly reduced by the presence of human recombinant leukocyte interferon (IFN alpha) in cultures of human peripheral blood mononuclear cells (PBMC). Mature natural killer (NK) cells can be depleted from PBMC with the toxic lysosomotropic agent L-leucine methyl ester. The generation of cytotoxic cells from lymphocytes depleted in leucine methyl ester was also inhibited by indicating that the IFN-alpha effect is not limited to mature cytotoxic NK cells. Depletion of adherent cells from PBMC did not affect the suppression of LAK induction by IFN-alpha. Surface marker analyses of Tac antigen and transferrin receptor (TfR) showed that the presence of IFN alpha throughout the culture period significantly suppressed the typical increase in IL-2-induced Tac- and TfR positive cells. In contrast, IFN alpha treatment before and after IL-2 culture enhanced LAK cytotoxic activity. Therefore, combinations of these biological response modifiers for clinical use should take into account the dual effect of IFN alpha on key features of the IL-2 response. PMID- 2598191 TI - Characterization of variant and parental-cross-protective immunity to immunogenic variants of a murine fibrosarcoma using the local adoptive transfer assay. AB - The purpose of this study was to characterize the lymphocyte populations responsible for rejection of immunogenic (Imm+) tumor variants, and the cross protective immunity engendered by Imm+ variants against the weakly immunogenic parental tumor. Immunogenic clones of the weakly immunogenic methylcholanthrene induced fibrosarcoma MCA-F have been generated using 1-methyl-3-nitro-1 nitrosoguanidine, 5-aza-2'-deoxycytidine, or ultraviolet radiation (UV-B; 280-320 nm). These clones grow progressively in immunosuppressed adult-thymectomized irradiated mice, but are rejected by immunocompetent syngeneic hosts. The parental MCA-F tumor grows progressively in both groups. Mice that have rejected a challenge of 1 x 10(5) Imm+ cells show an anamnestic immune response against both the Imm+ clone and the parental MCA-F tumor. Using the local adoptive transfer assay and depletion of T-cell subsets with antibody plus complement, we show that immunity induced by the Imm+ variants against the parent MCA-F was mediated by the Thy1.2+, L3T4a+ population without an apparent contribution by Lyt2.1+ cells. Although antivariant immunity was also dependent upon Thy1.2+ cells, depletion of either the L3T4a+ or the Lyt2.1+ cells failed to abolish immunity against the variant. A role for Lyt2.1+ T lymphocytes in antivariant immunity, but not antiparent immunity, was supported by the results of cytotoxic T lymphocyte (CTL) assays. Following immunization with high numbers (1 x 10(5) to 5 x 10(5) of viable Imm+ cells, antivariant, but not antiparent CTL activity was detected in mixed lymphocyte tumor cell cultures. Immunization with lower numbers (3 x 10(4] of viable Imm+ or with high numbers of mitomycin-C-treated Imm+ engenders only antivariant immunity without parental cross-protection. Under these conditions lymphocytes mediating immunity against the variant in the local adoptive transfer assay were exclusively of the Thy1.2+, L3T4a+ phenotype, with no contribution from the Lyt2.1+ cells. Identical results were obtained for Imm+ clones of MCA-F induced by methylnitronitrosoguanidine, 5-azadeoxycytidine, and UV-B, suggesting that the nature of the antitumor immunity engendered by Imm+ is not significantly affected by the agent used. Furthermore, these results demonstrate that the cross-reactivity and cellular effectors of antitumor immunity in this system are influenced by the immunizing dose of Imm+ cells: the predominant effectors of both antivariant and parental-cross-reactive immunity were of the CD4+ T cell subclass, with a CD8+ cytotoxic population contributing to antivariant immunity only after high-dose immunization. PMID- 2598194 TI - Heart failure. PMID- 2598193 TI - Human lymphokine-activated killer (LAK) cells. I. Depletion of monocytes from peripheral blood mononuclear cells by L-phenylalanine methyl ester: an optimization of LAK cell generation at high cell density. AB - Pretreatment of peripheral blood mononuclear cells (PBMC) with 5 mM L phenylalanine methyl ester (PheOMe) provides an efficient means to deplete monocytes. PheOMe does not affect the number of large granular lymphocytes after the pretreatment, but does inhibit natural killer cell cytotoxicity temporarily after the pretreatment. However, depletion of monocytes by PheOMe allows lymphokine-activated killer (LAK) cell generation with recombinant interleukin-2 (rIL-2) at high cell density (greater than 5 x 10(6) cells/ml). The time of the PheOMe pretreatment is 40-60 min, though some effect could be observed within 15 min, and the pretreatment could be performed at room temperature. Pretreatment density of PBMC with 5 mM PheOMe could be achieved at cell density up to 3 x 10(7) cells/ml. PheOMe-pretreated cells could be activated by rIL-2 in serumless media at high cell density. Pretreatment of PBMC with 5 mM PheOMe provides an efficient means to deplete monocytes, as compared to plastic and nylon-wool adherence. LAK cell generation is similar in both methods of monocyte depletion; therefore, depletion of monocytes allows, LAK cell generation at high cell density. The PheOMe procedure provides an improved and convenient process for preparing LAK cells for adoptive immunotherapy. PMID- 2598192 TI - Selective killing of carcinoembryonic-antigen (CEA)-producing cells in vitro by the immunoconjugate cytorhodin-S and CEA-reactive cytorhodin-S antibody CA208. AB - Cytorhodin-S, an anthracycline derivative, was covalently coupled to a monoclonal antibody (mAb) CA208, against carcinoembryonic antigen (CEA) in order to achieve selective killing of a CEA-producing colon carcinoma cell line, COLO 205. The conjugate (15 molecules of drugs/antibody) retained substantial antibody activity as well as drug activity as assessed by enzyme-linked immunosorbent assay and 24 h L1210 proliferation assay, respectively. Furthermore, the conjugate inhibited the growth of COLO 205 cells in a short-term cytostatic assay. This cytostatic effect of the immunoconjugate on COLO 205 cells was inhibited in a dose-dependent manner by pretreatment of the cells with unconjugated CA208 mAb. In addition, chloroquine, a lysosomotropic agent, inhibited the cytostatic effect of the immunoconjugate, indicating the involvement of lysosomal enzymes in releasing drugs from the immunoconjugate. The antibody (CA208) was significantly incorporated into the cytoplasm of COLO 205 cells as demonstrated by immuno electron microscopy. These in vitro results indicate that cytorhodin-S may be a good partner in immunoconjugates. However, in vivo animal experiments with the immunoconjugate revealed that the immunoconjugate was not so effective in prolonging survival. Thus, in vivo efficacy of this immunoconjugate remains to be further improved in application to cancer immunotherapy. PMID- 2598195 TI - Coronary angioplasty. PMID- 2598196 TI - The setting of coronary angioplasty in multivessel disease: current status and future directions. AB - In summary, the use of coronary angioplasty in the setting of multivessel coronary disease has become more common in recent years. Reports indicate that, in carefully selected patients, a high initial success rate and low incidence of complications can be achieved. We have presented a schema for the triage of multivessel disease patients. Examples of each subgroup have been presented to illustrate the basis for this categorization. Our experience using this schema at the San Francisco Heart Institute has been valuable in understanding the initial and long-term results of coronary angioplasty in these patients. It is important that this paradigm (or a similar classification schema) be adopted to assist clinicians in making judgments about alternative approaches in patients with multivessel disease and to provide a common organization for the dissemination of research findings and collaboration among members of the medical community. PMID- 2598197 TI - Percutaneous transluminal coronary angioplasty in patients over the age of 70 years. AB - Percutaneous transluminal coronary angioplasty was successfully performed in 207 of 242 patients over the age of 70 years. Multivessel disease was present in 71 per cent of patients; 93.0 per cent of patients had good left ventricular ejection fractions (greater than or equal to 35 per cent). Angioplasty was successful in 348 of 385 lesions dilated (90 per cent), with the desired degree of revascularization achieved in 90 per cent of patients with the dilatation of one or two lesions. The complications encountered included five Q wave infarctions (2.1 per cent), seven angioplasty-related deaths (2.9 per cent), and three emergency bypass surgeries (1.2 per cent). The cumulative probability of survival was 92 +/- 3 per cent at 63 months, and at a mean of 2.9 years 66 per cent of patients were angina-free. These data indicate that selected symptomatic coronary disease patients over the age of 70 years unsatisfactorily managed with medication have been successfully managed with coronary angioplasty. The results of coronary angioplasty compare favorably to those of coronary artery bypass surgery. PMID- 2598198 TI - Percutaneous transluminal coronary angioplasty in patients with severe left ventricular dysfunction. AB - Although bypass surgery can be utilized in the patient with impaired left ventricular function, the acute outcome (regarding morbidity and mortality) and long-term survival have significant associated problems. Percutaneous transluminal coronary angioplasty (PTCA) was implemented effectively as an accessory or alternative to coronary bypass surgery to treat obliterative coronary lesions in patients with severe ventricular dysfunction. The authors present data which indicate that PTCA should be considered in patients with left ventricular dysfunction as a primary therapeutic modality. PMID- 2598199 TI - Percutaneous cardiopulmonary support in high-risk angioplasty. AB - Percutaneous femoro-femoral cardiopulmonary bypass, cardiopulmonary support (CPS), has a role to play in the management of the high-risk coronary angioplasty patient. This article discusses the basic principles of cardiopulmonary bypass, technique, indications, complications, and future directions of this new addition to interventional cardiology. PMID- 2598200 TI - Nursing--a career in caring. PMID- 2598201 TI - Partial anodontia: a case report. AB - This article describes the multidisciplinary rehabilitation of a 20-year-old white man with partial anodontia. The patient presented with only three adult teeth; the remaining dentition was deciduous. The mandibular arch was restored with a tooth-supported overlay denture, while the maxillary arch received a fixed prosthesis. PMID- 2598202 TI - Intentional replantation. AB - When conventional endodontic treatment or retreatment and surgery are not feasible, a clinician may choose to replant the defective tooth. Intentional replantation consists of extracting the tooth, finding and correcting the defect, and replanting the tooth in its socket. This article describes five case reports in which intentional replantation was used as a last resort. Four (80%) of the five patients were successfully treated. PMID- 2598203 TI - Electric burns of the lip. AB - Young children, usually aged between 1 and 3 years, are frequent victims of electric burns of the lip caused by contact with an electric plug or extension cord. In this article, the authors classify the various types of lesions in 19 cases of electric burns of the lip and discuss surgical treatment approaches. PMID- 2598205 TI - The court's treatment of advertising by dentists. PMID- 2598204 TI - "Dry socket": etiology and management. AB - Dry socket is a postoperative complication that most oral surgeons will encounter with some frequency. Its etiology remains obscure, and prevention and management techniques vary considerably. This article will discuss probable etiologies of dry socket and its prevention and successful management. PMID- 2598206 TI - Chronic extraoral fistulae of dental origin. AB - Infections of dental origin may cause serious problems such as osteomyelitis and cutaneous fistulae. This article reviews 59 cases of extraoral fistulae of dental origin on the face and neck. The fistulae resolved after treatment of the intraoral lesion. Possible sources of such fistulae may be an obviously carious tooth, innocent-looking retained roots, or residual chronic dental infection of the maxilla or mandible. PMID- 2598207 TI - The interrelationship between periodontics and endodontics: report of a case. PMID- 2598209 TI - Custom matrix adaptation for concavities along cavosurface margins. PMID- 2598208 TI - Exodontic complications involving the maxillary sinus. PMID- 2598210 TI - Chemomechanical caries removal in endodontic therapy: selected applications. PMID- 2598211 TI - Sodium nuclear magnetic resonance imaging of acute cardiac rejection in heterotopic heart transplantation. AB - Nuclear magnetic resonance (NMR) imaging was used to measure tissue sodium-23 in the myocardium undergoing cardiac rejection. In six dogs, the donor heart was heterotopically transplanted into the recipient's chest cavity. The dogs were then killed and sodium-23 images of the excised hearts were obtained using a high field (1.5 Tesla) NMR imaging system. Proton NMR imaging of each excised heart was also performed and T1, T2 relaxation times were calculated. Subsequently, these data were correlated with pathological findings of mild, moderate and severe rejection. The correlation coefficients between the rejection score and the T1, T2 relaxation times and sodium NMR signal intensity were 0.79, 0.70 and 0.84, respectively. Severely rejected areas of the myocardium were visualised by increased sodium NMR signals. These findings suggest that an increase of sodium NMR intensity is mainly caused by an increase of intracellular sodium content due to irreversible myocardial necrosis. Sodium NMR allows evaluation of the location and extent of rejection of myocardium after heart transplantation. PMID- 2598212 TI - Platelet hyperreactivity and inefficient spontaneous thrombolysis in patients at high risk from an acute coronary event. AB - We conducted a retrospective study to correlate thrombotic variables with the risk from an acute coronary event, using a new in vitro technique, which measures haemostasis, thrombolysis and coagulation from non-anticoagulated blood samples. The analysis was based on data from 63 patients who had undergone exercise radionuclide ventriculography, 50 of whom were considered to be at risk from an acute coronary event because they satisfied at least one of the following three criteria: (1) coronary angiography documented disease, (2) prior myocardial infarction, (3) ventriculography assessed provocable ischaemia. Fifty matched normal subjects were used as controls. Significantly enhanced haemostasis was measured in patients considered at risk from acute coronary event, and haemostatic activity was further increased in patients with provocable ischaemia. Haemostasis in eight patients at risk (provocable ischaemia), who continued with the medication during the test, did not differ significantly from the controls. Greatly reduced spontaneous thrombolytic activity was measured in all patients at risk from acute coronary events. These findings suggest the presence of hyperactive platelets in patients at risk from acute coronary events, with an additional risk of greatly reduced spontaneous thrombolytic activity. PMID- 2598213 TI - Transection of aortic depressor nerve fails to raise blood pressure in spontaneously hypertensive rats. AB - Although central resetting via the aortic depressor nerve (ADN) has been known to occur in spontaneously hypertensive rats, the function of the ADN is not yet clear in these animals. To determine whether a baroreflex via the ADN can act to regulate blood pressure during hypertension, blood pressures were measured following ADN transection in spontaneously hypertensive and normotensive rats, and the reflex changes of heart rate and the sympathetic nerve activity were recorded during the pressor response to phenylephrine infusions. Blood pressures were significantly raised 1 day after ADN transections in normotensive rats and continued so for 7 d. Blood pressures were not changed in sham operated rats. In spontaneously hypertensive rats, ADN transections did not alter blood pressures in comparison with sham operated controls. On the seventh day after transections, all rats were anaesthetised with urethane and pressor responses to phenylephrine were examined. Bradycardic and sympathoinhibitory responses to the elevation of blood pressure caused by phenylephrine infusions were significantly smaller in ADN transectioned normotensive rats than in sham operated controls. In spontaneously hypertensive rats, the bradycardic and sympatho-inhibitory responses were not reduced by ADN transections. These findings suggest that the impaired baroreflex via the ADN can contribute to the development of hypertension in the spontaneously hypertensive rat. PMID- 2598214 TI - Lactate dehydrogenase and its isoenzyme activities in different parts of the normal human heart. AB - Activity and distribution of lactate dehydrogenase (LD) and its isoenzymes (LD1 5) were determined and both the heart (H) and muscle (M) subunit activities were calculated in myocardial samples from six brain dead human organ donors with normal hearts. Ten parts of each heart were analysed. LD1-3 were found to be the main LD isoenzymes. The LD1 activity predominated in all parts analysed. The activities of total LD, H subunit and LD1 increased from atria and auricular appendages via the right ventricle to the left ventricle. The H subunit activity varied more than twofold and the M subunit activity by only 20% between different locations of the heart. The left ventricular papillary muscle was found to have higher activities than other locations of both H and M subunits. It is concluded that the isoenzyme profile could be a metabolic adaptation to divergent work demand on the different heart chambers. PMID- 2598215 TI - Isoprenaline induced changes in ornithine decarboxylase activity and polyamine content in regions of the rat heart. AB - Isoprenaline stimulated increases in ornithine decarboxylase activity and polyamine content in cardiac tissues are implicated in macromolecular synthesis and cellular growth, but little is known about polyamine metabolism in functionally distinct regions of the heart. We therefore determined regional changes in ornithine decarboxylase activity and polyamine content in the right and left ventricles, septum, and the right and left atria of the rat following the administration of isoprenaline. An increase in ornithine decarboxylase specific activity and tissue polyamine content occurred in all cardiac regions, but the highest ornithine decarboxylase activity was found in the septum. Propranolol inhibited the isoprenaline stimulated ornithine decarboxylase activity in all the regions. Putrescine increased and peaked between 6 and 8 h in right and left ventricles and septum and declined to a control level by 12 h. Following a peak increase at 8 h, spermidine and spermine contents of both ventricles were maintained at peak levels, while those in the septum declined to control values by 12 h. There was no detectable putrescine in the right atria from the control experiments and in either atrium at 2 h following isoprenaline administration. Putrescine content peaked at 6 h in the right atrium and at 8 h in the left atrium and then declined. In both atria there was a peak increase in spermidine and spermine contents between 4 and 8 h. These results show that there is a regional variation in the accumulation of polyamines in the rat heart following isoprenaline administration. PMID- 2598216 TI - Effects of milrinone treatment in cardiomyopathic hamsters (CHF 147) with severe congestive heart failure. AB - The effects of oral milrinone treatment in cardiomyopathic hamsters with severe congestive heart failure (CHF) were evaluated. Strict criteria based on increase in body weight were established to define day no 1 of treatment. Survival rate of non-treated hamsters (group 1) ranged between 9 and 16 d, mean 12.9 (SEM 0.8) d, after entering the study. Hamsters treated with milrinone in drinking water (group 2a: 0.3 mg.ml-1, or group 2b: 0.6 mg.ml-1) survived between 6 and 36 d, mean 15.0(2.1) d, NS, for group 2a, and between 6 and 47 d, mean 19.6(4.0) d, NS, for group 2b. There was a significant difference between the number of hamsters that survived longer than 16 d between untreated hamsters (group 1, n = 0/12) and hamsters treated with milrinone (groups 2a, b, n = 7/24). There was no significant correlation between survival duration and milrinone daily dose nor between survival and milrinone plasma concentration at death. Milrinone treatment also significantly decreased pulmonary congestion as measured by the number of pigment containing macrophages per alveolus. No other pathological findings were modified by milrinone. It was concluded that, in addition to exerting a beneficial effect on pulmonary congestion, milrinone improved survival in some CHF hamsters. However, more studies are needed to evaluate the possibility of an arrythmogenic potential that might explain why some treated hamsters died earlier than non-treated hamsters. PMID- 2598217 TI - Effects of fish oil on arteriosclerosis in the Japanese quail. AB - The effects of fish oil on the development of arteriosclerosis were assessed using a special susceptible strain (SEA) of Japanese quail (Coturnix coturnix japonica). Sixty four quail were randomly divided into two groups and placed on isocaloric and approximately isocholesterolic (2% by weight) diets. Group A (control) was supplemented with 10% beef tallow oil, while group B received 10% Menhaden fish oil. The birds were sacrificed at 10 weeks (early) and 15-16 weeks (late). Based on semiquantitative histological grading of the arteriosclerotic lesions in the proximal aorta and brachiocephalic arteries, a score from 1 (no lesion) to 5 (severe, diffuse lesions) was assigned. A total of 57 quail were evaluated (seven died prior to scheduled sacrifice). At the early period, the mean arteriosclerosis scores for group A (n = 8) and group B (n = 8) were 3.3 (SD 1.0) and 1.9(1.0) respectively (p less than 0.017); 63% of the quail in group A and 13% of those in group B had a score greater than or equal to 3 (p less than 0.25, NS). At the late period, the scores for group A (n = 20) and group B (n = 21) were 3.8(0.6) and 2.6(0.9), respectively (p less than 0.001); 95% of the birds in group A and 43% of those in group B had a score greater than or equal to 3 (p less than 0.005). Histopathological examination of the arteriosclerotic lesions revealed disruption of the innermost elastic lamina, increased proteoglycan deposition in the medial interlamellar spaces, and the distinct involvement of macrophage like cells. Compared to human disease, arteriosclerosis in the quail is marked by distinct similarities, as well as differences. The SEA strain of Japanese quail appears to be a practical model for the study of arteriosclerosis; fish oil reduces the severity of disease in these birds when fed a high cholesterol diet. PMID- 2598219 TI - Time course of functional deterioration after coronary artery ligation in rats. AB - The aim of this study was to investigate the time course of deterioration of functional capacity in the rat after ligation of the left coronary artery. Functional capacity was evaluated from the increase in blood lactate concentrations in 109 rats during a standardised treadmill test. Animals with myocardial infarction were compared with sham operated and normal controls. Functional capacity was followed during a 13 week period and estimations of the functional capacity were performed 1, 3, 7, 9 and 13 weeks after infarction. Coronary artery ligation produced a significant reduction in functional capacity, averaging 47% (p less than 0.01) over the first 3 weeks after myocardial infarction, irrespective of infarct size. In rats with large infarcts, functional capacity remained essentially unchanged throughout the observation period, but rats with small infarcts improved gradually until their measured exercise response was completely normal at the end of the 13 week period. PMID- 2598218 TI - A geochemical basis for endomyocardial fibrosis. AB - Analysis of hearts of patients dying from endomyocardial fibrosis showed a significantly greater concentration of cerium, a lanthanide present in leafy vegetables and root tubers, than in control hearts. This may be important in the pathogenesis of the disease and provides a geographical basis for the prevalence of the disease in the tropics. PMID- 2598220 TI - Myocardial stiffness and reparative fibrosis following coronary embolisation in the rat. AB - The structural nature of fibrillar collagen involved in the replacement fibrosis which accompanies discrete areas of cell necrosis remains uncertain, as does its influence on the diastolic and systolic stiffness of the intact myocardium. This study, using 15 micron diameter microsphere embolisation of the rat myocardium, was undertaken to address these issues. Collagen volume fraction (trichrome), fibrillar collagens (picrosirius-polarisation technique), and the stress-strain relations of the intact myocardium (isolated hearts) were determined 30 d after the infusion of microspheres into the left ventricle. Significant differences from controls included: (a) the presence of hypertension secondary to renovascular embolisation; (b) a greater volume fraction of collagen that included not only a meshwork of short, taut appearing, thick and thin collagen fibres, interposed between muscle in areas of cell loss, but also a perivascular fibrosis involving intramyocardial coronary arteries; (c) elevated active stiffness, and (d) a more exponential diastolic stress-strain relation with increased stiffness at strains of 5% or more. These findings suggest that the replacement fibrosis accompanying myocyte necrosis has distinguishing morphological features involving fibrillar collagen and which because of its structure, alignment, and location relative to muscle leads to enhanced myocardial stiffness, including a more exponential rise in the diastolic stress strain relation. The perivascular accumulation of collagen suggests that additional factors other than microsphere induced necrosis were responsible for this reactive fibrosis. PMID- 2598221 TI - Importance of the redox state in vasoconstriction induced by adrenaline and serotonin. AB - The actin myosin system and the redox state have been implicated in a number of cellular functions and in many pathological conditions. To study the predictions of a new redox theory of actin-myosin interaction we examined the relationship between the redox state and vasoconstriction of rat aorta and dog basilar artery by adrenaline and serotonin. The results show that the contraction induced by these physiological agents can be inhibited and reversed by reducing agents. PMID- 2598222 TI - Pulmonary vasoconstrictor overreactivity in borderline systemic hypertension. AB - Raised vascular pressure and resistance and vasoconstrictor overreactivity to adrenergic stimulation are hallmarks of the pulmonary circulation in sustained primary hypertension. The aim of this study was to investigate the reasons for these disorders. In 10 males with borderline systemic hypertension, pulmonary haemodynamic variables were similar to those of an age matched group of eight normotensive subjects. In normotension, arithmetic and cold pressor tests (sympathetic activators) caused slight vasodilatation and vasoconstriction, respectively. In hypertension both tests showed an obvious vasoconstrictor effect. Restriction of blood flow through the lungs by distension of a balloon in the inferior vena cava is known to increase pulmonary vasoconstrictor reactivity in normal man. As a result of this manoeuvre, pulmonary pressure fell in the normotensive controls without variation in pulmonary vascular resistance, whereas in the hypertensive group there was an increase in resistance and the pressure did not change. In normotensive subjects with caval balloon, the sympathetic activating stimuli both became constrictor and caused vascular resistance to rise to the levels attained in the hypertensive patients during adrenergic stimulation in the absence of obstruction to venous return. In the hypertensives, these stimuli were not able to enhance the pulmonary vascular resistance further. This shows that in these patients maximal vasoconstriction was already achieved through the simple restraint of blood flow with vena caval obstruction. We suggest that in the early phases of systemic hypertension lung vessels are hypercontractile so that they overreact to hypoperfusion or to sympathetic stimulation, even before there is a stable rise in pressure and resistance. PMID- 2598223 TI - Model studies of the contribution of ventricular interdependence to the transient changes in ventricular function with respiratory efforts. AB - The effects of variations in intrathoracic pressure on left ventricular function were studied using a mathematical model of the circulation. The variations in intrathoracic pressure directly affect the left ventricular afterload, and indirectly alter left ventricular filling by changing the right ventricular volume. The decrease in intrathoracic pressure with sustained inspiratory efforts increased the left ventricular afterload and thus reduced the left ventricular stroke volume. Secondary to the reduction in stroke volume, the left ventricular end systolic and end diastolic volumes increased. Decreasing intrathoracic pressure also increased the systemic venous return, thereby increasing right ventricular volume. The model predicted that an enlarged right ventricular volume would, through diastolic ventricular interdependence, immediately reduce the left ventricular end diastolic volume (which in turn reduced the left ventricular stroke volume), while through systolic ventricular interdependence it would increase left ventricular stroke volume and reduce left ventricular end systolic volume. An increased right ventricular volume would also increase right ventricular stroke volume and after a delay of a few heart beats raise left ventricular end diastolic and stroke volumes. The net effect of respiratory variations in intrathoracic pressure on left ventricular function would be a combination of these effects. Thus on sustained inspiration the left ventricular stroke volume initially decreased (left ventricular afterload and diastolic interdependence secondary to the increase in right ventricular volume partly counteracted by the effects of systolic interdependence), followed by an increase as the increased venous return reached the left ventricle. The model indicated that the response to a forced expiratory effort was not simply the opposite of the inspiratory response, since the increase in intrathoracic pressure during a forced expiration is accompanied by increases in abdominal pressure. On sustained expiration the left ventricular stroke volume initially increased, with no significant initial change in end diastolic volume. The cardiovascular response to respiration is complex, and model studies can help to isolate and identify the various components involved. PMID- 2598224 TI - Collagen accumulation in heart ventricles as a function of growth and aging. AB - Increase in resting tension of left ventricular papillary muscle with age has been attributed to the amount of collagen present. We therefore studied the total amount and structure of myocardial collagen as a function of age in the hearts of male Fischer 344 rats. Using amino acid analysis and quantification of hydroxyproline, we showed that collagen accumulates in relation to ventricular protein after 3 months of age and continues in that mode with increased age of the animal, levelling off at 22 months. In this strain of rats, collagen increased in the left ventricle from 5.5% of total protein in a 1 month old animal to approximately 12% in 22 and 26 month old animals; in the right ventricle the increase was from 7% in the 1 month old animal to approximately 19.5% in 22-26 month old animals. The larger percentages of collagen in the right ventricle relative to the left agree with findings of others. Collagen accumulates in intrinsic collagenous structures where the pre-existing fibres are thickened and are more extensive. These structures were detected with light microscopy and scanning electron microscopy and include perimysial weaves, coiled perimysial fibres and struts. Regions of fibrosis were also increased in size and volume in older animals. PMID- 2598225 TI - Synthesis of subcellular protein fractions in the rat heart in vivo in response to chronic ethanol feeding. AB - An investigation was made into the chronic effects of ethanol on the subcellular protein fractions in the hearts of young rats (80-100 g body weight). Rats were fed a nutritionally adequate liquid diet containing ethanol as 36% of total energy. Controls were fed the same diet in which ethanol was substituted by iso energetic glucose. At the end of 6 weeks, rats were killed and hearts were fractionated into sarcoplasmic, myofibrillar and stromal protein fractions by differential solubilisation. The total myofibrillar protein content was significantly reduced by chronic ethanol feeding, though the contents of other fractions were relatively unaltered. The fractional and absolute rates of myofibrillar protein synthesis were significantly increased, but the synthesis rates of sarcoplasmic and stromal protein fractions were unaffected by ethanol feeding. This suggests independent regulation of myofibrillar protein content in the ethanol exposed heart. These changes may be responsible for alterations in myocardial function in alcoholic cardiomyopathy. PMID- 2598226 TI - Albumin interaction with caries-like lesions in bovine enamel. AB - The exposure of bovine enamel to an albumin-containing demineralizing solution results in penetration of protein into the porous enamel. Washing of this albumin containing enamel results in a complete (low pretreatment albumin concentrations) or partial removal of the albumin (pretreatment concentrations greater than or equal to 200 micrograms/ml-1). Subsequent exposure to increasing salt concentrations of fluoride, phosphate, calcium or chloride shows a partial removal of albumin at fluoride or phosphate concentrations of 75 mM while complete removal occurred at 150-200 mM fluoride or phosphate. Exposure to either calcium or chloride, even at 3 M concentrations, showed a negligible albumin release. It is proposed that protein removed at high fluoride or phosphate concentrations is bound by a strong interaction between protein-carboxyl groups and calcium on the surface of the enamel mineral. The partial removal of albumin released at low fluoride or phosphate concentrations indicates an enamel-albumin interaction by means of Ca-bridging between protein-carboxyl groups and mineral phosphates. Finally, it is suggested that salt-free washing removes albumin that has lost its native form upon binding to the partially dissolved crystallites of the enamel. It is concluded that enamel is mainly protected from demineralization by the inhibitory effects of protein penetrated into the pores, in addition to possible protection by the pellicle on the surface. PMID- 2598227 TI - Retention of glucose in oral fluid at different sites in the mouth. AB - Using glucose as a marker, a detailed study of retention at 5 different sites in the mouth of 1 subject and a less detailed examination of 4 selected sites in the mouths of 10 other subjects revealed site-specific differential patterns of oral retention (or clearance). These patterns seemed independent of sometimes large, absolute day-to-day variations in oral retention which occur in all subjects but appeared to vary somewhat between subjects, probably reflecting slight differences in the anatomy and physiology of the individual mouth. In general, the patterns resembled those recently derived from studies of other oral phenomena such as rates of diffusion out of plaque, fluoride uptake by mineral and hydrogen ion concentrations in plaque. They will dictate the concentrations and thereby influence the activity of all extraneous substances in different regions of the oral cavity and may relate to the site-specific patterns of oral disease. PMID- 2598228 TI - Kinetics of acquisition and loss of calcium fluoride by enamel in vivo. AB - Two in vivo experiments were performed, concerning (1) the kinetics of the acquisition of calcium fluoride on enamel during daily rinses with a solution of 0.023% F as sodium fluoride, and (2) the loss of calcium fluoride from enamel slabs which had been topically treated with a neutral solution containing 0.9% F as sodium fluoride. Enamel slabs were carried in the mouth by 6 volunteers for 8 days in both experiments. Sound and etched enamel were included. (1) During mouthrinses moderate amounts of fluoride were acquired by sound enamel, and more as calcium fluoride than as fluoridated apatite, whereas on etched enamel, more fluoride was deposited as fluoridated apatite. On etched enamel there was also a tendency that the deposition of calcium fluoride levelled out whereas the incorporation of firmly bound fluoride continued. This may indicate that calcium fluoride was transformed into fluoridated apatite, probably through remineralization during pH cycling in plaque covering the etched enamel. (2) After single topical application, it was found that etched enamel initially took up more calcium fluoride than sound enamel, but also lost more during the 1st day of in vivo exposure. The loss of calcium fluoride was arrested after 1-2 days, on sound enamel at 70% and on etched enamel at 40% of the original level. It is suggested that the increased amounts of firmly incorporated fluoride in enamel originated from calcium fluoride on enamel, and that calcium fluoride is an important and clinically significant source of fluoride ions on enamel. PMID- 2598229 TI - In vivo acid production from medicines in syrup form. AB - Syrup-form medicines have been shown to cause dental caries in chronically sick children. The acid production of 10 syrupy medicines sweetened with sucrose, fructose, sorbitol, xylitol and saccharin or with a combination of these was tested. The subjects consisted of 7 dental students with low buffering capacity and high levels of Streptococcus mutans. The subjects rinsed with sugar-based liquid medicines for 1 min, after which the plaque pH was measured with a Beetrode touch electrode at approximal sites until 40 min after the rinsing. The minimum pH, the delta pH, and the time under pH 5.7 were measured. From the results it can be concluded that xylitol, xylitol-saccharin and xylitol-sorbitol combinations used as sweeteners in syrup medicines are nonacidogenic, sorbitol is hypoacidogenic, and sucrose and fructose are highly acidogenic. PMID- 2598230 TI - Comparison of in vivo human dental plaque pH changes within artificial fissures and at interproximal sites. AB - Ion-sensitive field-effect transistor (ISFET) pH electrodes were used to monitor changes in plaque pH at the base of artificial occlusal surface fissures and at interproximal sites. Bovine enamel was used to construct fissures (1.5 x 0.1 x 1.0 mm) containing a small ISFET electrode. The fissures were fixed to carrier appliances and worn by 4 human volunteers. After plaque accumulation for 4 days changes in pH were monitored by wire telemetry following 1-min rinses with 10% solutions of either sorbitol or sucrose. Results were compared to data obtained from interproximal sites in the same subjects. Responses to sorbitol in the fissure and on the proximal surfaces were minimal and showed no significant difference in minimum pH (5.9 +/- 0.4 and 6.1 +/- 0.3, respectively) and area under pH 7.0. The response to sucrose at the two sites was very different revealing unique pH profiles which were statistically significantly different with regard to minimum pH (5.0 +/- 0.3, fissure and 4.3 +/- 0.2, proximal) and area under pH 5.7. Thus, the acidogenic potential of fermentable carbohydrate at two caries-prone sites in the human dentition is significantly different and conclusions based on interproximal telemetry measurements may not be applicable to occlusal surface fissures. PMID- 2598231 TI - Pattern of caries experience in permanent molars in a 15-year-old African population. AB - Some epidemiologic studies from Africa report higher DMF values in second than in first molars. It is generally accepted that the maturation of dental enamel influences the susceptibility of teeth to caries. The purpose of the present study was to test the hypothesis that DMF values of second molars will be higher than those of first molars if the first molars have reached a high degree of maturation before being exposed to increased cariogenic challenge. The study was carried out in a group of 15-year-old students attending secondary schools in Botswana (n = 287). The results showed that in children who assumingly had had a traditional diet during childhood the DMF values were higher in second molars than in first molars. In children who grew up in a more urbanized setting, the results were opposite. The observed differences were due to differences in caries experience in first molars only. The DMF values of second molars did not vary among the groups. Oral hygiene, sugar consumption and knowledge level at age 15 seemed to have no effect upon the caries pattern studied. It is concluded that the results support the hypothesis tested. PMID- 2598232 TI - Abstracts of papers presented at the 36th ORCA Congress. York, UK, July 12-15, 1989. PMID- 2598233 TI - [Death in old age--at home or in a hospital?]. AB - The author reflects critically on some shortcomings of the contemporary not always indicated increase of institutionalized death in old age. The relief of relatives from the physical and mental strain associated with nursing in the home is in many instances heavily paid for by emotional deprivation and psychological suffering of the dying person away from his home. The attending doctor should therefore consider more carefully all risks of hospitalization in particular the hastened onset of death (the so-called phenomenon of transplantation and translocation shock) against its possible advantages. Under conditions of hospital or institutional treatment it is important to improve systematically the emotional support of patients dying without their family (trained health workers, psychologists and clergymen) or facilitate legislatively and de facto the integration of the closest relatives in the process of dying. PMID- 2598234 TI - [Human interaction at the end of life. How can psychology help?]. AB - The author discusses psychological and ethical aspects of dying under conditions of hospitalization. He submits suggestions for the psychological personality training of a member of the attending staff for the encounter with the dying patient. He emphasizes the psychic adaptation of the attending staff by recognition, acceptation and a favourable influencing in relation to reality, to the subject himself and the dying patient. PMID- 2598235 TI - [Maturation of the patient's personality ante finem]. AB - The group of thanatological problems comprises also the question what happens in the patient's psyche in the last stage of his life. It was found that not only degeneration occurs but also the last stage of maturation of the personality. The author mentions concepts of maturation of the personality and characteristics of people coping well with the stress of death. Hardiness is a decisive characteristic of the personality of people who are a support for the dying. In the conclusion the author draws attention to the need to extend the curricula vitae of physicians by problems of philosophical anthropology. PMID- 2598236 TI - [Psychotherapeutic crisis intervention in ambulatory general practice]. AB - Psychotherapeutic crisis intervention is the term used for intervention implemented by the doctor dealing with a subject experiencing a mental crisis. Every doctor should be able to make this intervention. The authors recommend to apply the procedure they summarize in the following seven paragraphs: 1. The first step assisting a subject in mental crisis is to ensure conditions for an undisturbed talk; the patient should be received as somebody in whom we have personal interest. 2. We try to direct the interview quickly to the situation which has arisen and we concentrate on the patient's experience, we try to understand his problem and its causes. 3. If necessary, we engage the assistance of persons close to the patient, we mediate medical, social or legal assistance. 4. We consider the possibility of suicidal behaviour and select adequate preventive measures. 5. In indicated cases we offer short-term assistance by means of psychopharmaceutical preparations. 6. If the patient is motivated for another interview and the case calls for this cooperation, we offer it. We reach agreement on the time, frequency and approximate number of interviews. In the latter it is useful to proceed according to principles of non-directive psychotherapeutic talks. 7. If stabilization of the mental condition is achieved, we terminate after agreement with the patient the intervention. If the problems are rather "inside" the patient, we refer him for psychotherapeutic treatment. PMID- 2598238 TI - [Removal of a liver tumor using the Nd:YAG laser]. AB - At the Third Surgical Clinic, Charles University Prague a Nd:YAG laser, manufactured locally, MEDICALAS, was used to remove a hepatic tumour with a diameter of 3 cm. The authors used a continuous mode, a wavelength of 1064 nm, a non-contact focusing terminal and output of 100 W. The patient was discharged, healed, on the 11th day after operation. The operation which had no complications was the first of its kind in Czechoslovakia. PMID- 2598237 TI - [Ethical problems in modern genetics. Results of a questionnaire]. AB - New findings on the possible application of DNA diagnosis in the prevention of hereditary diseases are associated also with ethical problems of medical genetics. A questionnaire programme evaluated the views of respondents (743) on four groups of questions: 1. state of information on health status, 2. examination of members of the family, 3. compulsory treatment, 4. preventive measures. The authors sought mutual associations between the replies to individual questions and characteristics of respondents. Development of medicine calls for interdisciplinary health education and the solution of newly arisen ethical and legal problems. PMID- 2598239 TI - [20 years' therapy with high doses of chloramphenicol in bacterial inflammations of the meninges]. AB - The authors present their experience with the treatment of bacterial meningitis with large doses of chloramphenicol (200 mg/kg body weight per day by the i.v. route in three doses) in bacterial meningitis caused by common agents (i.e. Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis). They discuss the toxicity of chloramphenicol, complications, draw attention to contraindication of treatment with large doses. Treatment of bacterial meningitis with large doses of chloramphenicol is safe, if controlled as described. This is confirmed also by authors abroad. Cephalosporins of the third generation are indicated above all in bacterial meningitis caused by Gram-negative microorganisms. PMID- 2598240 TI - [Collagen as a biomaterial]. AB - The authors discuss the characteristics of different types of collagen, their incidence, structure, chemical composition and physical properties with regard to their use as biomaterial. They also mention the antigenicity, effect on platelet aggregation, cytodifferentiation and cellular proliferation. The authors discuss different biomedical applications of collagen and methods of its sterilization. PMID- 2598241 TI - [Experimental gerontology and the reliability theory]. AB - The reliability theory was elaborated for the estimation of the reliable action of technical systems. When it is applied to biological systems, it is important to characterize unequivocally the disorder which will substantially after the reliable activity of the entire organism or of individual systems. The authors investigated in their experiments during the postnatal development of rats changes in the erythrocyte stability. The age-conditioned decline was evaluated as a disorder. The erythrocyte stability was assessed in animals of different age, i. e. in 4-, 6-, 10-, 18- and 24-month-old animals by the method of the haemolytical action of brilliant cresyl blue in isotonic NaCl solution. The results of experiments suggest that when red cells were incubated in isotonic NaCl solution only, there was no difference in the lysis of erythrocytes in different age groups. However, when they were incubated in isotonic NaCl with brilliant cresyl blue, there was a significantly greater haemolysis in red cells of 4-, 18- and 24-month-old rats, as compared with the lysis of red cells from 6- and 10-month-old animals. Red cell lysis conditioned by brilliant cresyl blue in relation to age is discussed from the aspect of the reliability theory. PMID- 2598242 TI - [Results of radionuclide ventriculography in normal children and adolescents]. AB - In order to assess the range of normal values of radionuclide ventriculography the authors selected retrospectively 53 normal children and adolescents. All were examined by radionuclide angiocardiography on account of clinical and echocardiographical suspicion of congenital heart disease with a left-to-right shunt; a significant shunt was, however, excluded. In all patients after equilibration of the radiotracer ventricular function was examined by radionuclide ventriculography. The authors evaluated the usual volume, time and rate characteristics. The normal range was defined as the mean +/- 2 standard deviations which is for the ejection fraction of the left ventricle 47 to 72% and for the ejection fraction of the right ventricle 31 to 56%. The other results are discussed in detail in the text. PMID- 2598243 TI - [Acute states in colorectal surgery]. AB - The authors evaluate their own group of 80 patients treated in the acute stage of colorectal disease during the period between 1980-1987 at the First Surgical Clinic, Faculty Hospital with Policlinic, Olomouc. Fifty-five patients treated by the classical three-stage operation with a lethality of 51%, 25 patients treated by primary resection with a lethality of 31%. The encouraging immediate and long term results of rationally indicated acute resections are not in favour of three stage operations. PMID- 2598244 TI - [Reconditioning of diabetics--a progressive therapeutic method]. AB - The authors discuss an untraditional comprehensive therapeutic method of diabetes where in 30 patients marked improvement of parameters of the carbohydrate and lipid metabolism was achieved. The value of the mean fasting blood sugar level declined from 11.28 mmol/l to 5.28 mmol/l, fructosamine declined from 2.54 mmol/l to 2.01 mmol/l. Total cholesterol declined from 6.93 mmol/l to 6.32 mmol/l and triacylglycerols from 3.69 mmol/l to 2.69 mmol/l. Improvement of the objective and subjective health status of the patients and their better cooperation with health workers suggest ways to be selected in future years for preventive trends of our health services. The interest of patients in the success of the programme signalizes the so much needed active attitude to problems of the subjects' own health. PMID- 2598245 TI - [The effect of erythropoietin on lymphocyte and granulocyte functions in dialyzed patients]. AB - The authors investigated the influence exerted on some lymphocyte and granulocyte functions during treatment with human recombinant erythropoietin in five female patients with renal failure due to chronic interstitial nephritis, who were included in a regular dialyzation programme. The authors revealed a significant increase of the candidacidal capacity of phagocytizing cells of the peripheral blood stream and an increased capacity of blastic transformation of lymphocytes after stimulation with the mitogen phytohaemagglutinin. In these changes the improved oxygen metabolism may participate by a correction of anaemia, when this preparation is administered, but it cannot be ruled out that erythropoietin interferes by some hitherto unknown mechanism with immune processes. PMID- 2598246 TI - [Use of the isoradial chamber in the preparation of thrombocyte concentrates using the Travenol CS-3000 separator]. AB - During intensive treatment of haemoblastoses it is important to administer repeatedly high-quality platelet concentrates. The authors describe the first results obtained with the use of an isoradial chamber of Travenol Co. for separation on a CS-3000 separator. Using the chamber, they achieved in the first 20 patients a reduction of the separation time by 30 mins. (23%) and the thrombocyte yield was not reduced. The resulting product contained, however, more leucocytes. The chamber can be used to reduce the separation period also under Czechoslovak conditions where donors have smaller numbers of thrombocytes than reported by western authors (the microcomputer of the separator is set for a regime suited for larger thrombocyte numbers). PMID- 2598247 TI - [Modern views on nutritional status evaluation]. AB - The author analyzes the four main areas of nutritional status assessment in hospitalized patients: 1. Assessment of bodily reserves of energy and protein, 2. Assessment of the functional capacity where damage caused by malnutrition can be assumed, 3. Estimation of the extent of metabolic stress, 4. An attempt to unify the procedure as regards interpretation and prognosis. Clinical research provides many methods and data which can be used for the evaluation and monitoring of the nutritional status, for giving nutritional support by parenteral nutrition of optimal quantity and quality. It is, however, necessary to elaborate feasible diagnostic methods which can be used in special departments as well as in standard hospital practice. PMID- 2598248 TI - [Incidence and developmental interdependence of peripheral nerve disorders in type 1 diabetics]. AB - In 1987-1988 the authors subjected to comprehensive neurological examination 79 type I diabetics. The group comprised subjects under 60 years and patients with other possible neurotoxic influences were eliminated. After a detailed clinical examination in 75.9% diabetics clinical signs of affection of the peripheral nervous system were revealed, incl. 45.6% clinical diabetic neuropathies were detected. In all instances it was symmetrical distal sensory or sensomotor polyneuropathy and in four instances moreover the carpal tunnel syndrome was detected. The most frequent neurological disorder was panhypaesthesia on the acra of the lower extremities. The most frequent subjective complaint were paraesthesias of the feet and subsequent cramps. The authors investigated moreover parameters of the long-term compensation of diabetes, the duration of diabetes and the biological age of diabetics. They assessed the statistical significance of these parameters for the development of diabetic neuropathy which was proved only for the parameter of the duration of the disease and the biological age of type I diabetics (p less than 0.05). PMID- 2598249 TI - [Incidence and developmental interdependence of peripheral nerve disorders in type 2 diabetics]. AB - In 1987-1988 160 type 2 diabetics, dispensarized in diabetological out-patient departments of the medical clinic of the Institute for Postgraduate training were subjected to neurological examinations. The selection of the group was governed by an effort to reduce to a minimum the association of other neurotoxic influences. The group therefore comprised subjects under 60 years of age; diabetics with other diseases with a possible neurotoxic action, drug abuse, alcohol abuse, etc. were eliminated. After a detailed neurological examination signs of affection of the peripheral nervous system were detected in 87.5%, clinically manifest diabetic neuropathy was found in 78 diabetics (48.75%); 12 had moreover mononeuropathy of the median nerve. The clinical picture was uniform: impaired perception of vibrations on the acra of the lower extremities with ascendent propagation, reduction to disappearance tendinous-muscular reflexes on the lower extremities. Subjectively more frequently cramps of the feet than paraesthesias were reported. The authors revealed that long-term compensation of diabetes, the duration of diabetes and the biological age of the diabetics were statistically significant for the manifestation of diabetic neuropathy. This significance was proved for the factor of biological age (p less than 0.05); there was also a significant correlation between the long-term state of compensation of type 2 diabetes and the manifestation of neuropathy (p = 0.06). PMID- 2598250 TI - [Long-term clinical course in the anomalous origin of coronary arteries]. AB - The authors analyze in a retrospective investigation the clinical picture of 15 adult patients (12 men and 3 women) with an abnormal origin of the coronary arteries, diagnosed from a total of 5500 coronarographic examinations made in the Institute for Clinical and Experimental Medicine. In four patients the anomaly was isolated and in 11 patients it was associated: in six with coronary disease, in three with rheumatic heart disease and in two with an atrial septal detect. The authors evaluate the long-term clinical course by check-up ambulatory examinations after time intervals of 64.6 +/- 45.7 months following the coronarographic examination. The long-term course was favourable in the four patients with the isolated anomalous origin of the coronary arteries. In patients with an associated anomalous origin of the coronary arteries and other heart disease the long-term course was not favourable. Two patients died, two suffered a myocardial infarction, one suffered from angina and one from cardiac dysrhythmia. The authors assume that the complications developed mainly due to the associated heart disease, congenital or acquired. The objective physical finding, ECG and X-ray finding of the heart and lungs did not change significantly in the meantime. It appears thus that an isolated anomalous origin of the coronary arteries may be a relatively benign disease. The prognosis of the patients depends above all on associated heart disease or other diseases. PMID- 2598251 TI - [Possibilities of treatment of erectile disorders by the administration of vasoactive substances into the penis using iontophoresis]. AB - The authors applied to 18 men with erection disorders vasoactive substances by iontophoresis of the penis. In 12 patients partial improvement was achieved, in four marked improvement. Only in two the condition was not influenced. The applied method is non-invasive, practically without negative side-effects. It can extend the range of therapeutic methods in psychogenic and mild organic erection disorders. PMID- 2598252 TI - [Microalbuminuria--a risk indicator for the development of nephropathy in insulin dependent diabetics]. AB - The authors submit preliminary results of a prospective study in 65 insulin dependent diabetics with a varying duration of the disease where they followed up the development of microangiopathic organ changes in relation to the compensation of diabetes and the development of clinically manifest proteinuria or albumin excretion (microalbuminuria). From the results ensues that in recent and postrecent patients the increased albumin excretion is as a rule only a manifestation of metabolically conditioned and treatable changes of renal function and is of minor importance for the prediction of the risk of development of diabetic nephropathy. In patients with prolonged duration of diabetes the position is not unequivocal and if the albumin excretion persists or increases despite intensive insulin treatment it is most probably an indicator of a high risk of development of diabetic nephropathy. PMID- 2598253 TI - [Idiopathic membranous glomerulonephritis. Clinico-morphologic relations and prognosis]. AB - Membranous glomerulonephritis (GN) was diagnosed in 61 of 993 patients with histologically confirmed primary GN. Two-thirds of the patients were men. High hypertension was recorded in 7.5% of the patients. A typical finding was marked proteinuria (6.15 +/- 4.88 g/24 h.) with mild erythrocyturia (median 8 million in Addis sediment). At the time of biopsy 86% of the patients had normal creatininaemia, the level of which was positively correlated with the blood pressure and degree of tubulointerstitial regression. The cumulative duration of renal function in 5, 10 and 20 years was 88, 80 and 57%; during the same time intervals 22, 48 and 52% of the patients were cured. PMID- 2598254 TI - [Results of colonoscopic examination 2 years after polypectomy of an intestinal adenoma]. AB - The authors examined 204 patients after a two-year interval following endoscopic and surgical polypectomy resp. of an adenoma of the large intestine. The group comprised 67 patients (32.8%) with a metachronous adenomatous polyp. In none of these patients carcinoma was diagnosed. In patients where originally a solitary adenoma was diagnosed a metachronous adenoma developed in 14%. In the group with originally synchronous polyps a metachronous polyp developed in 85.2%. The male:female ratio during the original examination and after two years in relation to an adenoma of the large intestine did not change significantly. The test for occult blood in the faeces made by the Haemoccult test gave in 3% falsely positive results and in 27% falsely negative results. According to the results of the examination the two-year interval is sufficient for repeated coloscopy within the framework of dispensarization of patients after polypectomy. In exceptional cases the interval of the check-up must be adjusted to the patient's condition with regard to the follow up by and collaboration with the general practitioner. PMID- 2598255 TI - [5-Fluorocytosine. A neglected systemic antimycotic in Czechoslovakia]. AB - The authors submitted a detailed characteristic of the properties of 5 fluorocytosine and its applicability in the treatment of mycoses. They emphasize the advantages of pharmacokinetic parameters of this systemic antimycotic preparation and the possibility to combine it with amphotericin B. Based on their own results of laboratory tests they give an account of the spectrum of sensitive and resistant mycotic agents. According to the authors 5-fluorocytosine is not sufficiently appreciated in Czechoslovakia and it deserves more attention. PMID- 2598256 TI - [Acute myocardial infarct in a 15-year-old patient]. AB - The authors present the case-history of a 15-year-old sportsman with acute "non Q" myocardial infarction. The disease is associated with excessive physical strain and subsequent protracted paroxysm of supraventricular tachycardia with severe hypotension. The paper is supplemented by ECG tracings and laboratory findings, echocardiographic, scintigraphic, coronarographic and other examinations. Pathological changes of the coronary arteries, or preexisting metabolic disease or myocardial disease, valvular defects or congenital anomalies were not confirmed. The authors draw attention to the possible occurrence of myocardial infarction also in very young subjects as a result of excessive physical strain along with other possible pathogenetic mechanisms. PMID- 2598257 TI - [Health problems in Laos]. PMID- 2598258 TI - Detection of circular forms of eliminated DNA during macronuclear development in E. crassus. AB - Following their sexual cycle, hypotrichous ciliated protozoa transform a copy of a chromosomal micronucleus into a macronucleus containing small, linear DNA molecules. A frequent event during macronuclear development is the removal of short segments of DNA (internal eliminated sequences: IESs) by a process equivalent to DNA breakage and rejoining. In this study we used a polymerase chain reaction procedure to demonstrate that free circular forms of IESs are present in cells undergoing macronuclear development. Sequencing of the junctions of the free circular IESs suggests that they share 12 nucleotides with the macronuclear DNA molecules that are generated following IES removal. The results provide evidence that IESs are removed by an active DNA breakage and rejoining process, which may involve staggered cuts in the substrate DNA. PMID- 2598259 TI - The V(D)J recombination activating gene, RAG-1. AB - The RAG-1 (recombination activating gene-1) genomic locus, which activates V(D)J recombination when introduced into NIH 3T3 fibroblasts, was isolated by serial genomic transfections of oligonucleotide-tagged DNA. A genomic walk spanning 55 kb yielded a RAG-1 genomic probe that detects a single 6.6-7.0 kb mRNA species in transfectants and pre-B and pre-T cells. RAG-1 genomic and cDNA clones were biologically active when introduced into NIH 3T3 cells. Nucleotide sequencing of human and mouse RAG-1 cDNA clones predicts 119 kd proteins of 1043 and 1040 amino acids, respectively, with 90% sequence identity. RAG-1 has been conserved between species that carry out V(D)J recombination, and its pattern of expression correlates exactly with the pattern of expression of V(D)J recombinase activity. RAG-1 may activate V(D)J recombination indirectly, or it may encode the V(D)J recombinase itself. PMID- 2598260 TI - Primary antibody-forming cells and secondary B cells are generated from separate precursor cell subpopulations. AB - Two precursor cell subpopulations have been isolated from the spleen cells of nonimmune mice. The major B cell subpopulation binds high levels of the J11D monoclonal antibody and, upon T cell-dependent antigenic stimulation, gives rise to primary antibody-forming cell clones but not secondary B cells. A minority of the 10%-14% of Ia+ precursors that bind low levels of J11D (J11Dlo) also generate antibody-forming cell clones after primary stimulation. However, over 70% of J11Dlo precursors yield no primary antibody-forming cell clones but instead give rise to secondarily responsive B cells. The existence of a distinct precursor cell subpopulation that is responsible for the generation of B cell memory is further evidenced by the distribution of variable region clonotypes among J11Dlo primary precursors, which resembles the clonotype patterns of secondary B cells, and by the accumulation of somatic mutations in their clonal progeny. PMID- 2598261 TI - Regulation of RNA polymerase III transcription in response to F9 embryonal carcinoma stem cell differentiation. AB - B2 genes are rodent-specific middle repetitive elements transcribed by RNA polymerase III. They are expressed in the ectoderm and mesoderm but not in the embryonic or extraembryonic endoderm of early mouse embryos. This tissue specificity is mimicked in vitro by embryonal carcinoma and embryonic stem cell lines. Nuclear run-on experiments show that the down-regulation of B2 genes during F9 embryonal carcinoma cell differentiation into endoderm occurs at the transcriptional level and that other class III genes, including those encoding tRNA, show a similar response. We have used cell-free extracts to investigate the molecular mechanisms responsible. The specific down-regulation of transcription by RNA polymerase III during F9 cell differentiation is due to a reduction in the activity of the general class III transcription factor TFIIIB. PMID- 2598262 TI - Amplification, expression, and packaging of foreign gene by influenza virus. AB - A system is described that allows use of recombinant DNA technology to modify the genome of influenza virus, a negative-strand RNA virus, and to engineer vectors for the expression of foreign genes. Recombinant RNA is expressed from plasmid DNA in which the coding sequence of the influenza A virus NS gene is replaced with that of the chloramphenicol acetyltransferase gene. When transfected with purified influenza A virus polymerase proteins--in the presence of helper virus- the recombinant RNA is amplified, expressed, and packaged into virus particles, which can be passaged several times. The data indicate that the 22 5' terminal and the 26 3' terminal bases of the influenza A virus RNA are sufficient to provide the signals for RNA transcription, RNA replication, packaging of RNA into influenza virus particles. PMID- 2598263 TI - Posttranscriptional trans-activation in cauliflower mosaic virus. AB - The ability of plant cells to translate dicistronic mRNAs that mimic a segment of the polycistronic 35S RNA from cauliflower mosaic virus has been tested. The chloramphenicol acetyltransferase and beta-glucuronidase open reading frames (ORFs) were fused in-frame to the second viral cistron (ORF I). Efficient reporter expression from the corresponding plasmids in plant protoplasts was observed only upon cotransfection with viral DNA. The trans-activating gene maps at ORF VI, which is expressed from a separate, monocistronic messenger (19S RNA). Deletion analysis shows that trans-activation selectively enhances downstream gene expression; the high expression of the upstream ORF is not further increased. The major reporter transcript remained bicistronic upon trans activation, and its abundance varied only to a limited extent. Results indicate that trans-activation enhances the translation of downstream ORFs on polycistronic mRNAs derived from cauliflower mosaic virus. PMID- 2598264 TI - Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. AB - Transgenic mice that overproduce the hepatitis B virus large envelope polypeptide and accumulate toxic quantities of hepatitis B surface antigen (HBsAg) within the hepatocyte develop severe, prolonged hepatocellular injury that initiates a programmed response within the liver, characterized by inflammation, regenerative hyperplasia, transcriptional deregulation, and aneuploidy. This response inexorably progresses to neoplasia. The incidence of hepatocellular carcinoma in this model corresponds to the frequency, severity, and age of onset of liver cell injury, which itself corresponds to the intrahepatic concentration of HBsAg and is influenced by genetic background and sex. Thus, the inappropriate expression of a single structural viral gene is sufficient to cause malignant transformation in this model. These results suggest that severe, prolonged cellular injury induces a preneoplastic proliferative response that fosters secondary genetic events that program the cell for unrestrained growth. PMID- 2598265 TI - The graded distribution of the dorsal morphogen is initiated by selective nuclear transport in Drosophila. AB - The maternal morphogen dorsal (dl) plays a key role in the establishment of dorsal-ventral polarity in Drosophila. We present evidence that the graded distribution of dl protein is initiated by selective nuclear transport. The dl protein is uniformly distributed throughout the cytoplasm of early embryos, but approximately 90 min after fertilization, dl protein present in ventral but not dorsal regions is selectively transported to the nucleus. Mutations in maternally active genes that regulate dl disrupt this transport process, resulting in an inactive, cytoplasmically localized form of the dl protein. Selective nuclear transport of dl protein was reproduced in tissue culture cells. The wild-type dl protein is largely restricted to the cytoplasm, while truncated proteins are predominantly localized within the nucleus. Transient cotransfection assays suggest that dl activates expression from several promoters in an apparently sequence-independent manner. We discuss the role of nuclear transport as a regulated process in gene expression and development. PMID- 2598266 TI - Relocalization of the dorsal protein from the cytoplasm to the nucleus correlates with its function. AB - dorsal is one of the maternally active dorsal-ventral polarity genes of Drosophila and is homologous to the vertebrate proto-oncogene c-rel. In wild-type embryos, the dorsal protein is found in the cytoplasm during cleavage. After the nuclei migrate to the periphery of the embryo, a ventral-to-dorsal gradient of nuclear dorsal protein is established. The formation of the nuclear gradient is disrupted in mutant embryos from other maternally active dorsal-ventral polarity genes: in dorsalized embryos only cytoplasmic protein is observed, while in ventralized embryos the nuclear gradient is shifted dorsally. My findings suggest that nuclear localization is critical for dorsal to function as a morphogen and that the distribution of the dorsal protein determines cell fate along the dorsal ventral axis. PMID- 2598267 TI - Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells. AB - Cells from the human leukemia cell line HL-60 undergo terminal differentiation when exposed to inducing agents. Differentiation of these cells is always accompanied by withdrawal from the cell cycle. Here we describe the isolation of a cDNA encoding a novel serine protease that is present in HL-60 cells and is down-regulated during induced differentiation of these cells. We have named this protease myeloblastin. Down-regulation of myeloblastin mRNA occurs with both monocytic and granulocytic inducers. Myeloblastin mRNA is undetectable in fully differentiated HL-60 cells as well as in human peripheral blood monocytes. We found that regulation of myeloblastin mRNA in HL-60 cells is serum dependent. Inhibition of myeloblastin expression by an antisense oligodeoxynucleotide inhibits proliferation and induces differentiation of promyelocyte-like leukemia cells. PMID- 2598269 TI - You need not be alone anymore. PMID- 2598268 TI - The use of the Ross implant in an immediate extraction site. PMID- 2598270 TI - Airways and appliances. PMID- 2598271 TI - Rehabilitation. PMID- 2598273 TI - Some of the swi genes of Schizosaccharomyces pombe also have a function in the repair of radiation damage. AB - In Schizosaccharomyces pombe the frequency of mating-type (MT) switching is reduced by mutations in the swi genes. The ten hitherto known swi genes can be subdivided into three classes: Ia, Ib and II. Strains having swi5 (class Ib), swi9 (class II) and swi10 (class II) mutations do not only show reduced MT switching, but also exhibit an increased sensitivity to UV- and gamma-rays. For that reason, 19 previously described rad genes were tested for their effect on MT switching. We found that swi9, "rad10", "rad16" and "rad20" are allelic with each other indicating that the former allocation of these rad mutations to three different genes must have been erroneous. Among the remaining 16 rad genes examined, rad22 seems to be a new class II swi gene. The double mutants swi5 swi9 and swi5 swi10, but not swi9 swi10, are much more sensitive to radiation than the respective single mutants. Thus a cumulative increase in sensitivity occurs only if the mutants belong to different classes; previously the same correlation was found with regard to cumulative effects in MT switching. PMID- 2598272 TI - cDNA of the 24 kDa subunit of the bovine respiratory chain NADH dehydrogenase: high sequence conservation in mammals and tissue-specific and growth-dependent expression. AB - We have isolated and sequenced several overlapping cDNA clones from a bovine lambda gt10 library which encode all but the first five amino acids of the entire mature 24 kDa subunit of NADH:ubiquinone oxidoreductase (EC 1.6.99.3), the first enzyme of the respiratory chain. The derived amino acid sequence agrees with that determined by direct sequencing of the purified protein, filling in a gap in the published sequence. A comparison of the nucleotide and amino acid sequences of the bovine 24 kDa subunit with those recently determined for the rat homologue has shown that this nuclear-encoded subunit of an OX-PHOS complex has diverged in these two species much less than the mitochondrial DNA-encoded subunits of the same enzyme complex, and also less than a set of available non-mitochondrial nuclear DNA-coded proteins. The sequence analysis of the clones has revealed the expression in the brain of two mRNAs differing in the length of the 3' untranslated region. Furthermore, two polyadenylated RNA species, 930 and 1080 nucleotides in length, probably corresponding to the above mRNAs, have been detected in bovine brain and other tissues by RNA gel blot hybridization. The level of expression of the 24kDa subunit gene varies by more than an order of magnitude among different tissues. A cross-hybridizing mRNA species of 930 nucleotides has also been observed in HeLa cells and found to be strongly growth regulated. PMID- 2598274 TI - Characterization of the termini of linear plasmids from Nectria haematococca and their use in construction of an autonomously replicating transformation vector. AB - The mitochondria of isolate FS37 from Nectria haematococca mating population I (Fusarium solani f. sp. cucurbitae) contain two linear plasmids, pFSC1 and pFSC2, of 9.2 and 8.3 kbp, respectively. Evidence for a protein blocking the 5' termini of these plasmids was obtained from exonuclease digestion experiments. A single protein band with an apparent Mr of 80 K was labeled when the DNA-protein complex of either plasmid was reacted with [125I] Bolton-Hunter reagent and then digested with DNase I. DNA sequence analysis of the termini of both plasmids revealed long inverted repeats of 1,211 bp (pFSC1) and 1,027 bp (pFSC2). No sequence similarity was found between the terminal inverted repeats (TIRs) of pFSC1 and pFSC2, nor was any similarity identified between the TIRs of these plasmids and sequences of TIRs from other linear DNAs. A restriction fragment containing the TIR of pFSC1 conferred autonomous replication when incorporated into an integrative transformation vector of Ustilago maydis. PMID- 2598275 TI - Sequence analysis of the tRNA(Tyr) and tRNA(Lys) genes and evidence for the transcription of a chloroplast-like tRNA(Met) in maize mitochondria. AB - The nucleotide sequences of three tRNA genes and their flanking regions from the maize mitochondrial genome is reported. These genes, which are located in the same region of the genome between the 14-kb inverted repeats, are transcribed in the mitochondria and code for tRNA(Lys) (anticodon UUU) tRNA(Met) (CAU) and tRNA(Tyr) (GUA). The very high homology shown by the tRNA(Met) gene with its chloroplast counterpart indicates that it probably originates from a chloroplast DNA insertion. The analysis of the upstream regions of these genes showed that the tRNA(Tyr) and the tRNA(Lys) genes possess the consensus sequence AAGAANRR, which could act as a promoter sequence in higher plant mitochondria. PMID- 2598276 TI - The genes of both subunits of ribulose-1,5-bisphosphate carboxylase constitute an operon on the plastome of a red alga. AB - Plastid (pt) DNA from the red alga Porphyridium aerugineum was purified by CsCl gradient centrifugation. An EcoRI library of the ptDNA was screened with a gene probe specific for the gene encoding the large subunit (LSU) of ribulose-1,5 bisphosphate carboxylase/oxygenase (Rubisco EC 4.1.1.39) from spinach. A 5.8 kb EcoRI clone containing the LSU gene (rbcL) was isolated and the DNA sequence of the Porphyridium rbcL gene and its flanking regions was determined. An open reading frame was found 130 bp downstream from the rbcL gene that shows homology to genes coding for the small subunit of Rubisco (rbcS) from higher plants and cyanobacteria. Both genes (rbcL + rbcS) are cotranscribed. Comparison of rbcL and rbcS sequences from Porphyridium, higher plants and cyanobacteria seems to reveal a remarkable evolutionary distance between the plastids of the red algae (rhodoplasts), chloroplasts and cyanobacteria. PMID- 2598277 TI - Dispersed repetitive sequences in the chloroplast genome of Douglas-fir. AB - Restriction mapping and DNA sequencing were used to characterize dispersed repetitive DNA in the chloroplast genome of Douglas-fir [Pseudotsuga menziesii (Mirb.) Franco]. To map repeat families, chloroplast DNA (cpDNA) clones were hybridized at high stringency to one another and to cpDNA cut with restriction enzymes. Repeats are clustered in four regions of the genome and comprise at least six families. Sequence analysis of one repeat family shared among three XbaI fragments indicated the presence of a 633 bp inverted repeat which contains a complete tRNA-Serine (GCU) gene and a highly conserved open reading frame (ORF 3.6). Both ends of this 633 bp dispersed repeat have a transposon-like combination of short direct and inverted repeats. One copy of the repeat flanks one of the endpoints of a major inversion which differentiates Douglas-fir from tobacco cpDNA. Dispersion of repetitive DNA by transposition, coupled with loss of the large inverted repeat, appears to have predisposed conifer cpDNA to a number of inversions. An 8 bp (CATCTTTT) direct repeat in tobacco is located between two inverted sections in Douglas-fir; it may be a target sequence for homologous recombination. PMID- 2598278 TI - [The tunnel syndrome from the aspect of industrial neurology]. PMID- 2598279 TI - [The reflex response in the abductor pollicis brevis muscle after tapping the distal segments of the fingers, the ulnar olecranon and scapular acromion. Electromyographic study]. AB - The author made an electromyographic investigation of reflex responses in the abductor pollicis brevis muscle abductor pollicis brevis muscle after percussion with a hammer on the dorsal, lateral, palmar, medial and distal surface of the distal digit of the thumb, on the dorsal and palmar area of the distal digits of the other fingers and also on the olecranon ulnae and acromion scapulae. The investigation was made to detect the influence of the site of percussion on the character of the reflex response. The reflex responses were examined during slight isometric contraction of the muscle. After averaging rectification and of the recorded potentials the reflex responses were identified as excitatory and inhibitory modulation of the basal muscular activity depending on the inducing stimulus. Excitatory parts of the reflex response with a short latency were recorded after percussion on the lateral, dorsal and palmar area of the distal digit of the thumb and after percussion of the dorsal area of distal digits of the other fingers and after percussion of the palmar area of the little finger. As to other sites where reflexes were evoked first the inhibitory part of the reflex response was recorded. Excitation parts of reflex responses with a medium latency were obtained from all sites where reflexes were evoked. Late-latency parts of the reflex response had an inconstant occurrence. The results of the investigation provided evidence of a short-latency proprioceptory; influence of the abductor pollicis brevis muscle from synergic muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598280 TI - [Transplantation of embryonic brain tissue into newborn rats after unilateral bulbectomy]. AB - Embryonic tissue (E14-E16) of the olfactory bulb and substantia nigra resp. was transplanted to neonatal rats into cavities formed by partial or total unilateral bulbectomy. After 40 days of survival the animals were perfused with Bouin's fluid and processed for histological examination. Complete series of 10 microns horizontal or sagittal sections were stained with Gill haematoxylin and Bodian's silver method. To demonstrate the olfactory protein immunohistochemical staining with peroxidase-antiperoxidase was used. After bulbectomy degeneration of the axons of the olfactory cells occur, which subsequently regenerate, penetrate into the transplant and form typical glomerular structures in the latter. By immunohistochemical staining in both types of transplants olfactory structures were reliably differentiated from non-olfactory elements. PMID- 2598281 TI - [The effectiveness of antiplatelet therapy in ischemic cerebrovascular attacks in the chronic stage]. AB - Sixty-nine patients, mean age 50.0 years with an ischaemic cerebrovascular attack in the carotid circulation were subjected since 1983 to a complete examination incl. cerebral angiography. Based on the case-history, clinical examination, evaluation of results of cerebral angiography, haematological examination focused on platelet aggregation and statistical evaluation, the author assessed the shortest necessary period of the use of antithrombocytic drugs. One year after the attack a significant effect of the use of these drugs was proved, after two years, however, the H0 hypothesis on the independence of the clinical condition and treatment cannot be refuted. Based on these results the author recommends that to these stabilised patients after two years from the attack drugs should not be administered as a matter of routine; the patients should be subjected to a clinical examination and examination of circulating platelet aggregates with the possibility to discontinue antithrombocytic treatment. The author discusses the method of W. U. Hoak for the evaluation of the effectiveness of antithrombocytic treatment. PMID- 2598282 TI - [Epilepsy and the speed of learning motor skills]. AB - In 64 epileptics (mean age 35.7 years, mean onset of the disease at the age of 12.1 years) the author used a test of learning a series of movements (TOSP B). It involves the performance of a series of three asymmetrical movements maximal speed of learning is evaluated. Patients with epilepsy have a significantly reduced rate of motor learning, as compared with two comparable group of healthy subjects (104 and 67 subjects). Patients with a favourable course of the disease (n = 24) are significantly quicker than patients with an adverse development of the disease (n = 40). The author discusses the revealed significant correlation with the duration of the disease, contact with psychiatry, later onset of the disease, IQ and education, Contrary to expectations, the correlation with age was not significant, the factor of the disease being more important than the factor of ageing. Tests of asymmetrical movements are sensitive for the detection of relatively subclinical symptoms of cerebral affections. They prove useful as a stable part of neuropsychological examinations in epileptic patients. PMID- 2598283 TI - [Personal experience with strain-induced diseases--neurologic aspects]. AB - The author summarizes his experience with diseases of the locomotor system of the extremities caused by long-term, excessive unilateral overload (item 29 of the Czechoslovak "List of occupational diseases") assembled during the period 1976 to 1987. In the department for occupational diseases of the District Institute of National Health Pardubice 349 subjects were examined where the disease was suspected, in 93 workers the occupational affection was notified. From a total of 2,294 notified occupational during the above period disease due to overload accounted for 4.1%. The cause of the affection was most frequently bursitis (32x), epicondylitis (25x) and carpal tunnel syndromes (24x), other affections being less frequent. The author analyzed the results with regard to sex, age, period of exposure, occupation. Special attention was devoted to glass workers who accounted for 51.6% of all affected subjects. The author discusses possible neurological affections, i. e. damage of the peripheral nerves. In the assessment of disease caused by overload the authors emphasized the importance of close cooperation of specialists for occupational diseases, neurologists, orthopaedists, physiologists and specialists in hygiene of work. PMID- 2598284 TI - [Visual and somatosensory evoked potentials in hereditary motor-sensory neuropathies]. AB - Visual (VEP) and somatosensory evoked potential (SEP) were examined in 31 patients with hereditary motor-sensory neuropathy (HMSN); in the great majority HMSN type I was involved. A prolonged latency of P100 was found only in the two oldest patients, the amplitude of this wave was, however, in adult patients, as compared with the control group, significantly reduced. On examination of SEP a typical finding were N9,N13 waves which were difficult to assess and a spinal wave with markedly prolonged latencies of N20 and P40. The amplitude of these cortical components declined with advancing age. Rather surprisingly the most severe affection of the peripheral sensory and motor neuron was found in the youngest generation of children, while in the older generation of parents the central affection was more marked. PMID- 2598285 TI - [Incidence of craniostenosis in data from the pediatric neurologic department with emphasis on children of gypsy origin]. AB - The authors analyzed in material extending over twenty years from the neurological department of the regional paediatric hospital in Kosice the incidence of craniostenosis, focused on gypsy children, as compared with the number of population in the East Slovakian region of the gypsy ethnic group, and the incidence of the disease in non-gypsy children. Analysis revealed a relatively increased incidence of craniostenosis in children of gypsy origin--a total of 0.11% cases, while the incidence in children of non-gypsy parents was 0.01%. In both groups boys predominated over girls. In some non-gypsy children also developmental anomalies were detected which thus could be classified into syndromes. By early screening and early surgical operation it is possible to prevent inferior development of thus affected children as well as serious sequelae with a fatal outcome. PMID- 2598286 TI - [Suggestions for comprehensive rehabilitative care in cerebrovascular disorders within the framework of the cerebrovascular program (discussion)]. PMID- 2598287 TI - A case of anisakiasis--Alberta. PMID- 2598288 TI - Leprosy in Canada to 1988. PMID- 2598289 TI - Lyme disease vector, Ixodes dammini, identified in Quebec. PMID- 2598290 TI - Expanded programme on immunization (EPI) poliomyelitis in 1986, 1987, and 1988. PMID- 2598291 TI - [Related features in the development of social consciousness in the area of health care and the living environment]. AB - The author provides evidence of the mutual association of human health and a healthy living environment. From the nature of processes which influence health and the living environment ensues also the similarity of the reflection of this problem in the social consciousness. The author draws attention in particular to the danger of underrating of those types of health damage and harmful environment which are manifested only perspectively after a long time. To prevent this damage it is useful to influence ecological awareness and health awareness of the population by active social training and active social participation. PMID- 2598292 TI - [The injury rate and tactics for health promotion]. AB - The authors draw attention to possibilities of a marked reduction of the injury rate based on a statistical investigation and analysis of the causes and sources of injuries. The injury rate is the second most important cause of impaired health and is the most important cause of loss of the living and working potential in Czechoslovakia. The main cause of injuries is the human factor; therefore injuries are to a considerable extent avertible and can be influenced to a considerable extent. Areas of frequent injuries which have been for a long time the object of perfect records, analysis and social action such as e.g. the injury rate at work or during transport have an unequivocal declining tendency as far as the number of deaths and severe casualties is concerned. The paper reveals hitherto statistically not recorded areas of injuries and risk groups of the population on which investigations and preventive measures against injuries should be focused. PMID- 2598293 TI - [Aspects of social and health problems in the aged in the Kosice-Nove Mesto District]. AB - The author presents the results of repeated examinations of a group of 725 old people on the records of the geriatric welfare centre of the district Kosice-Nove mesto. Attention is paid to medico-social needs of old people, their demands, to the extent and quality of care and housing conditions. Some suggestions are presented for the health and social services. PMID- 2598294 TI - Glutathione depletion and cytotoxicity by naphthalene 1,2-oxide in isolated hepatocytes. AB - The ability of naphthalene 1,2-oxide to diffuse across intact cellular membranes, the subsequent biotransformation of this epoxide and its potential to produce losses in cellular viability have been examined in incubations of isolated hepatocytes. Addition of 1R,2S- or 1S,2R-naphthalene oxide enantiomers (15, 30 and 60 microM) to isolated hepatocytes resulted in a rapid depletion of intracellular glutathione. Depletion of glutathione was concentration dependent and maximal at 5-15 min. Addition of either of the enantiomeric oxides at 60 microM resulted in the loss of more than 20 nmol glutathione/10(6) cells (1 ml cells); thus more than a third of the added epoxide was available for conjugation with intracellular glutathione. The time course and concentration dependence of glutathione depletion corresponded to the rapid, concentration-dependent formation of naphthalene oxide glutathione conjugates. The levels of glutathione adduct were highest 1 min after addition of naphthalene oxide and declined to 25% of this level after 30 min. Loss of glutathione conjugates from incubations correlated with the formation of N-acetylcysteine adducts. In contrast, the levels of glutathione adducts added exogenously to hepatocytes were relatively stable over a 120-min incubation suggesting that although further metabolism of naphthalene oxide glutathione adducts formed intracellularly is possible, extracellular glutathione adducts cannot penetrate the hepatocellular membrane. Small amounts of radiolabel from [3H]naphthalene 1,2-oxide were bound covalently to macromolecules in hepatocytes; the rate of this binding slowed rapidly after the first minute of incubation. Severe blebbing of the surface of the hepatocytes was noted in cells incubated for 30 min with 480 microM naphthalene oxide. Many of the cells were vacuolated at 60 min and progressed to frank necrosis with pyknotic nuclei and inability to exclude trypan blue. Cells incubated with 1 naphthol responded in a qualitatively similar fashion to those cells incubated with epoxide; however, hepatocytes incubated with 1-naphthol progressed to frank cellular necrosis at a slower rate. In hepatocytes partially depleted of glutathione by pretreatment with buthionine sulfoximine, addition of 1S,2R naphthalene oxide at a rate of 1 nmol/min/10(6) cells resulted in significant losses in cell viability. In contrast, no losses in cell viability were observed with the enantiomer, 1R,2S-naphthalene oxide. Both epoxides produced similar losses in cellular glutathione levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2598295 TI - Time course of selenite metabolism in confluent cultures of mouse mammary epithelial cells. AB - The distribution of 75Se selenite in various macromolecules over time was evaluated in confluent cultures of the LMA mouse mammary epithelial cell line. 75Se label did not distribute equally to all fractions at the same time point. The label initially entered the selenonucleic acid fraction and subsequently increasing quantities were detected in the selenoprotein fraction. The time period of increasing inhibition of DNA synthesis correlated with increasing levels of selenoproteins. The major selenoprotein found in this time frame in confluent phase LMA cells was an acidic, 58K selenoprotein. PMID- 2598297 TI - Effect of thiols on lipid peroxidation in rat liver microsomes. AB - The stimulatory or inhibitory effects of various thiol compounds on in vitro lipid peroxidation by iron-ascorbate in rat liver microsomes were determined. Glutathione had no measurable pro-oxidant capacity, in contrast, it protected against lipid peroxidation. N-Acetyl l-cysteine and S-methyl-glutathione had no effect on in vitro lipid peroxidation. l-Cysteine stimulated lipid peroxidation and also of d-penicillamine and dl-dithiothreitol the pre-oxidant capacity predominated the anti-oxidant capacity. Cysteamine afforded a pronounced protection against in vitro lipid peroxidation. In contrast to the labile character of the glutathione dependent protection, the protection by cysteamine was not affected by heat-pretreatment of the liver microsomes or alkylating protein sulfhydryl groups by N-ethyl maleimide. Again in contrast to glutathione, the protection against in vitro microsomal lipid peroxidation by cysteamine was not reduced after in vivo lipid peroxidation induced by CC14. This suggests that even after the process of lipid peroxidation has been started, administration of cysteamine might still be beneficial. PMID- 2598296 TI - Alteration of precocene II-induced hepatotoxicity by modulation of hepatic glutathione levels. AB - Precocene II (6,7-dimethoxy-2,2-dimethyl-2H-benzo[b]pyran), an insect growth regulator that is structurally related to several naturally occurring carcinogenic and non-carcinogenic alkenylbenzenes, is genotoxic and produces hepatic centrolobular necrosis in rats. This investigation was conducted to evaluate the effects of modulation of hepatic glutathione levels on the toxicity of precocene II. Administration of a toxic dose of precocene II (175 mg/kg) to male Sprague-Dawley rats rapidly depleted hepatic GSH, produced histopathological changes in the liver, and induced increases in serum aminotransferase activity. Concurrent administration of the cysteine pro-drug L-2-oxothiazolidine-4 carboxylic acid (OTC) prevented these toxic effects of precocene II. In contrast, pretreatment of rats with DL-buthionine-SR-sulfoximine (BSO), an inhibitor of glutathione synthesis, potentiated the toxicity of an otherwise non-toxic dose of precocene II (100 mg/kg). These results indicate that glutathione is important for protection from precocene II-induced hepatotoxicity. PMID- 2598298 TI - Reduction of hexavalent chromium in a reconstituted system of cytochrome P-450 and cytochrome b5. AB - The reduction of hexavalent chromium (Cr(VI] by the monooxygenase components was studied. Both a reconstituted system of cytochrome P-450 (P-450) and cytochrome b5 (b5) with NADPH was capable of reducing Na2CrO4 (30 microM) provided anaerobic atmosphere. The rates were 1.29 nmol Cr.min-1 nmol P-450(-1) and 0.73 nmol Cr.min 1 nmol b5(-1). Using NADH instead of NADPH gave very low reducing activities, confirming the enzymic nature of the P-450 dependent Cr(VI) reductase reaction. Oxygen, 22% (air) and 0.1% gave 89% and 69% inhibition of Cr(VI) reducing activity, respectively. Carbon monoxide (100%) caused an inhibition of about 37% and 44% for P-450 and b5, respectively. Externally added flavin mononucleotide (FMN) (3 microM) or Fe-ADP (10 microM) to the complete system stimulated the enzymatic reaction about 2-fold and 3-fold, respectively. PMID- 2598299 TI - Structure-activity relationships of airway irritating aliphatic amines. Receptor activation mechanisms and predicted industrial exposure limits. AB - Sensory irritation due to inhalation of diethyl-, triethyl-, dibutyl-, tributyl- and cyclohexylamine was estimated from the decrease in respiratory rate in normal mice (American Standard Method E981-84). The concentration-effect relations followed Michaelis-Menten equations, except for diethylamine, for which a threshold was found. The concentrations depressing the respiratory rate by 50% (RD50) for diethyl-, triethyl-, dibutyl- and cyclohexylamine were 184, 186, 81 and 27 ppm, respectively. For tributylamine the maximum response was too low to achieve a RD50 value. Pulmonary irritation was estimated from the decrease in respiratory rate in tracheal-cannulated mice. The respective concentrations depressing the respiratory rate by 50% (tRD50) were 549, 691, 101, 96 and 78 ppm for diethyl-, triethyl-, dibutyl-, tributyl- and cyclohexylamine. Only minor or no effects on the tidal volumes were found at the lower exposure concentrations. The trigeminal and pulmonary receptors are believed to be activated directly by the amines, and the receptor environments are believed to be lipophilic. Structure-activity analysis was made by comparing the effects of the amines with the effects of previously investigated primary n-alkylamines. Occupational exposure limits (TLV) were estimated for both effects. Finally, the sensory irritation effect was found to be an important part of the odour sensation, also below the TLVs. PMID- 2598300 TI - The in vitro interaction with DNA of several hypoxic radiosensitizers. AB - The five 5-nitroimidazole derivatives and the four glyoxylic compounds tested in this paper for their interaction with DNA with and without irradiation had previously been reported to act as radiosensitizers at a cellular level. Our aim was to find if the radiosensitizing activity of these products could be due to their interaction with DNA. For this purpose the formation of a complex was tested by comparing the spectrophotometrical absorbances of (DNA-product) solutions with those of DNA and of the products, at the absorption maxima of the products. None of the products formed in vitro a complex with DNA. The irradiation of product solutions with and without DNA induced a molecular degradation of the product which was linearly correlated with the radiation dose. The G values characterizing this radiodegradation showed that the presence of DNA did not modify the radiosensitivity of the products, neither in aerobic nor under hypoxic irradiation conditions. These results proved that the radiosensitizing properties of these compounds cannot be attributed to their chemical interaction with DNA. PMID- 2598301 TI - O6-methylguanine-DNA methyltransferase activity in tissues and cells of the rat respiratory tract. AB - A product of alkylating agents and DNA, O6-methylguanine (O6-MG), can mispair with thymine, resulting in initiation of a carcinogenic tissue response. O6 alkylguanine-DNA alkyltransferase (AGT) is an acceptor protein responsible for repairing O6-MG. The purpose of our experiments was to characterize in vitro AGT activity in tissues and cells in the respiratory tract, a target tissue for inhaled alkylating agents. Anatomically defined regions throughout the respiratory tract of male F344 rats were obtained. These included two regions of the lateral wall of the left and right nasal airway (maxilloturbinates and ethmoturbinates), trachea, extrapulmonary bronchi and peripheral lung. Alveolar type II cells were also used in these studies. Radioactive 3H-methylated DNA was synthesized for use in all experiments. Removal of [3H]methyl from O6-MG was measured by high-pressure liquid chromatography after incubation for up to 30 min of tissue and cell extracts with the [3H]DNA. With the exception of tracheal and bronchial extracts, all tissues and cells analyzed contained AGT activity, which was found to increase proportionally to the amount of protein added to reaction flasks. AGT activity in tracheal and bronchial extracts was only detected at the highest protein concentration used (1.5 mg protein/ml) and ranged from 10-15 fmol/mg protein. AGT activity was highest in the lung (integral of 75 fmol/mg protein) and a region of the nasal tissue, the ethmoturbinates (integral of 45 fmol/mg protein). AGT activity in the maxilloturbinates was about 50% less than the AGT activity measured in the ethmoturbinates. These data suggest that methylated DNA in specific regions of the rat respiratory tract should be readily repaired, albeit to different extents. PMID- 2598302 TI - In vitro and in vivo modulation of the bioactivation of 4-(methylnitrosamino)-1 (3-pyridyl)-1-butanone in hamster lung tissues. AB - The metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by hamster lung explants was studied. The three major metabolic pathways were alpha-C hydroxylation (activation), pyridine N-oxidation (deactivation) and carbonyl reduction. alpha-C-Hydroxylation and pyridine N-oxidation were linear with time (0.5-5 h) and number of explants per dish (3-10). Addition of [2 (diethylamino)ethyl 2,2-diphenylpentenoate] hydrochloride (SKF-525A) to the culture medium reduced alpha-C-hydroxylation and pyridine N-oxidation. alpha-C Hydroxylation was enhanced by treatment of the hamsters with the two cytochrome P 450 inducers, phenobarbital and 3-methylcholanthrene. These results suggest that cytochrome P-450 monooxygenases are involved in the activation of NNK by alpha-C hydroxylation. Three groups of hamsters were fed a control diet or diet supplemented with 2% 2(3)-tert-butyl 4-hydroxyanisole (2(3)-BHA) or given a 0.002% solution of (S)-nicotine to drink for two weeks. Lung explants were then cultured with NNK in vitro. Treatment with 2(3)-BHA and (S)-nicotine induced the alpha-C-hydroxylation pathways. Pyridine N-oxidation was increased by (S) nicotine treatment. These results indicate that dietary factors and tobacco smoke components can modulate the metabolism of NNK. PMID- 2598303 TI - Effects of fluorine substitution on the DNA binding and tumorigenicity of benzo[b]fluoranthene in mouse epidermis. AB - The effects of fluorine substitution on benzo[b]fluoranthene (B[b]F) DNA adduct formation and tumorigenicity in mouse epidermis were investigated. Fluoro derivatives studied included 1-, 6-, 7-, 8-, 9- and 11-fluoroB[b]F as well as 1,9 and 6,9-difluoroB[b]F. Each compound was applied topically to mice and hydrocarbon/DNA adduct formation was assessed using the 32P-post-labelling technique. All of the fluorinated compounds bound to DNA to a lesser extent than B[b]F. Among the fluorinated compounds, the greatest binding was observed for 8 fluoroB[b]F. Lowest levels of hydrocarbon/DNA adduct formation from the fluoro derivatives were observed for 1-, 7-, 11- and 6,9-difluoroB[b]F. The tumor initiating activities on mouse skin of 7-, 9- and 11-fluoroB[b]F were determined. All three compounds were significantly less tumorigenic than B[b]F. The results of this study are discussed with respect to possible mechanisms of metabolic activation of B[b]F. PMID- 2598304 TI - Lipid peroxidation-dependent and -independent protein thiol modifications in isolated rat hepatocytes: differential effects of vitamin E and disulfiram. AB - Exposure of isolated rat hepatocytes to allyl alcohol (AA), diethyl maleate (DEM) and bromoisovalerylurea (BIU) induced lipid peroxidation, depletion of free protein thiols to about 50% of the control value and cell death. Vitamin E completely prevented lipid peroxidation, protein thiol depletion and cell death. A low concentration (0.1 mM) of the lipophylic disulfide, disulfiram (DSF), also prevented the induction of lipid peroxidation by the hepatotoxins; however, in the presence of DSF, protein thiol depletion and cell death occurred more rapidly. Incubation of cells with a high concentration (10 mM) of DSF alone led to 100% depletion of protein thiols and cell death, which could not be prevented by vitamin E. The level of free protein thiols in cells, decreased to 50% by exposure to AA, DEM and BIU, could be reversed to 75% of the initial level by dithiothreitol (DTT) treatment, indicating that the protein thiols were partially modified into disulfides and partially into other, stable thiol adducts. The 100% depletion of protein thiols by DSF was completely reversed by DTT treatment. The involvement of lipid peroxidation in protein thiol depletion was studied by measuring the effect of a lipid peroxidation product, 4-hydroxynonenal (4-HNE), on protein thiols in a cell free liver fraction. 4-HNE did not induce lipid peroxidation in this system, but protein thiols were depleted to 30% of the initial value, irrespective of the presence of vitamin E. DTT treatment could reverse this for only 25%. Similar, DSF-induced protein thiol depletion could be reversed completely by DTT. We conclude that (at least) two types of protein thiol modifications can occur after exposure of hepatocytes to toxic compounds: one due to interaction of endogeneously generated lipid peroxidation products with protein thiols, which is not reversible by the action of DTT, and one due to a disulfide interchange between disulfides like DSF and protein thiols, which can be reversed by the action of DTT. PMID- 2598305 TI - Crystal and molecular structures of carbon-bridged pyrimidine cyclonucleosides. Substrate analogs of ribonuclease A. AB - The crystal and molecular structures of carbon-bridged 6,5'-cyclo-5'-deoxy-4 thiouridine (6,5'-Cs4U), 6,5'-cyclo-5'-deoxy-2',3'-O-isopropylideneuridine (6,5' CiU) and 6,6'-cyclo-5',6'-dideoxy-allofuranosyluracil (6,6'-CU) have been determined by X-ray diffraction. The molecular conformations of 6,5'-Cs4U and 6,5'-CiU are very similar; the conformation about the glycosidic bond is anti (low region), the torsion angle O(4')-C(1')-N(1)-C(2) being -150.0 degrees for 6,5'-Cs4U and -145.5 degrees for 6,5'-CiU, and the sugar puckering being both O(4')-exo. On the other hand, 6,6'-CU takes the glycosidic torsion angle of 116.9(4) degrees (middle anti region) and the sugar conformation of C(4')-endo. The cyclization causes little alteration in the geometry of the base moiety. 6,5' Cs4U and 6,5'-CiU exhibit the similar base-base interactions between adjacent molecules, although their molecular packings are quite different; the 4 thiouracil or uracil moiety interacts with adjacent base moieties through hydrogen bonding and stacking interactions. In 6,6'-CU, cyclonucleosides were connected by hydrogen bondings between the hydroxyl and sugar ring oxygen atoms and between the hydroxyl groups and the base nitrogen and oxygen atoms. As the 2',3'-cyclic phosphates of these carbon-bridged cyclonucleosides are hydrolyzed by ribonuclease A, it is suggested that the conformers found in these cyclonucleosides are recognized by the enzyme. PMID- 2598306 TI - Preparation of chiral, highly functionalized cyclopentanes and its application to the synthesis of prostaglandin E1. AB - This paper describes the preparation of the polyfunctionalized cyclopentane ((+/ )-5) by silica gel-catalyzed air-oxidation, and its kinetic resolution by means of microbial reduction with Rhodotorula rubra to afford optically pure (-)-5 (greater than 99% ee). Starting with (-)-5, a new route to prostaglandin E1 was established. PMID- 2598307 TI - Biosynthesis of chaetochromin A, a bis(naphtho-gamma-pyrone), in Chaetomium spp. AB - The biosynthesis of chaetochromin A, a metabolite of Chaetomium gracile, has been studied using [13CH3]methionine, sodium [1-13C]acetate, sodium [1,2-13C2]acetate, sodium [1-13C,2,2,2-2H3]acetate, and sodium [1-13C,1,1-18O2]acetate as precursors. The folding pattern of the polyketide chain in chaetochromin A, biosynthesized from sodium [1,2-13C2]acetate as the precursor, was determined to be the same as that of rubrofusarin by carbon-13 nuclear magnetic resonance (13C NMR) analysis. By using [13CH3]methionine as a precursor, the source of 2-CH3 was determined. When sodium [1-13C,2,2,2-2H3]acetate was fed, a beta-isotope-shifted peak was observed only for carbon 2. In the 13C-NMR spectra of chaetochromin A and of its hexamethyl ether derived from sodium [1-13C,1,1-18O2]acetate, isotope shifted peaks were observed for carbons 4, 5, 6, 8 and 10a, but not for carbon 2. These results showed that oxygen 1 originated from the same unit of acetate as carbon 10a. PMID- 2598308 TI - Tannins and related compounds. LXXXIV. Isolation and characterization of five new hydrolyzable tannins from the bark of Mallotus japonicus. AB - A chemical examination of the bark of Mallotus japonicus (Thunb.) Mueller-Arg. (Euphorbiaceae) has led to the isolation of five new hydrolyzable tannins (16 20), together with fourteen known tannins (1-14). On the basis of chemical and spectroscopic evidence, the structures of compounds 16 and 17 were established as 1,2-di-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-beta-D-glucose and 1-O-digalloyl 3,6-(R)-hexahydroxydiphenoyl-beta-D-glucose, respectively, while compounds 18 (mallojaponin) and 19 (mallonin) were shown to be 1-O-galloyl-2,4 elaeocarpusinoyl-3,6-(R)-valoneayl-bet a-D-glucose and 1-O-galloyl-2,4 elaeocarpusinoyl-beta-D-glucose. Compound 20 (mallotusinin) was characterized as a novel ellagitannin which possesses a unique 1,1'-(3,3',4,4' tetrahydroxy)dibenzofurandicarboxyl group. On the other hand, examination of the leaves revealed the presence of hydrolyzable tannins (8-10, 12-15) all containing a beta-D-glucopyranose core with 1C4-conformation. Furthermore, the orientation of the valoneayl group in mallotinic acid (13) and mallotusinic acid (14), which had remained unclarified, was determined on the basis of 1H-13C shift correlation spectral analysis and chemical correlations. PMID- 2598309 TI - Condensed thienopyrimidines. I. Synthesis and gastric antisecretory activity of 2,3-dihydro-5H-oxazolothienopyrimidin-5-one derivatives. AB - A practical preparation of various 2,3-dihydro-5H-oxazolo[3,2-a]thieno[3,2-d]-, [3,4-d]-, and [2,3-d]pyrimidin-5-one derivatives was developed starting from the corresponding aminothiopheneesters in two steps, and their chloro-substituted derivatives were prepared. These compounds were evaluated for gastric antisecretory activity in pylorus-ligated rats, compared to the anti-ulcer standard, cimetidine, and their structure-activity relationships are discussed. PMID- 2598310 TI - Studies on antibacterial agents. I. Synthesis of substituted 6,7-dihydro-1-oxo 1H,5H-benzo[i,j]quinolizine-2-carboxylic acids. AB - A series of substituted 6,7-dihydro-1-oxo-1H,5H-benzo[i,j]quinolizine-2 carboxylic acids was synthesized and tested for antibacterial activities. Among them, 9-fluoro-6,7-dihydro-5-methyl-8-(4-methyl-1-piperazinyl)-1-oxo-1H,5H- benzo[i,j]quinolizine-2-carboxylic acid (OPC-7241) exhibited potent antibacterial activity against gram-positive and -negative bacteria, including Staphylococcus aureus and Pseudomonas aeruginosa, and 9-fluoro-6,7-dihydro-8-(4-hydroxy-1 piperidyl)-5-methyl-1-oxo-1H, 5H-benzo[i,j]quinolizine-2-carboxylic acid (OPC 7251) showed potent activity characteristically against Propionibacterium acnes. PMID- 2598311 TI - Synthesis of novel 2-chloro-1,4-dihydropyridines by chlorination of 2-hydroxy-1,4 dihydropyridines with phosphorus oxychloride. AB - Novel 2-chloro-1,4-dihydropyridine derivatives were synthesized by chlorination of 2-hydroxy-1,4-dihydropyridines with POCl3. The dihydropyridines chlorinated at position 2 exhibited more potent vasodilative and hypotensive activities than the dihydropyridines (nicardipine and nitrendipine) with a methyl group at position 2. PMID- 2598312 TI - Condensed thienopyrimidines. II. Synthesis and gastric antisecretory activity of thiazole and polymethylene condensed thienopyrimidine derivatives. AB - Thiazolo[3,2-a]thieno[3,2-d]-, [3,4-d]- and [2,3-d]pyrimidin-5-one derivatives (6, 11 and 16), and polymethylene condensed thieno[3,2-d]-, [3,4-d]- and [2,3 d]pyrimidin-5-one derivatives (19-21), in which the oxygen atom of the oxazolidine moiety in 3 was replaced by a sulfur atom or methylene groups, were synthesized and evaluated for gastric antisecretory activity in pylorus-ligated rats. The structure-activity relationships of these compounds are discussed. PMID- 2598313 TI - Preparation and comparative properties of antisera against glyco-3 beta,12 alpha dihydroxy-5-cholen-24-oic acid linked to bovine serum albumin at the C-3, C-15 alpha, and C-24 positions. AB - Anti glyco-3 beta,12 alpha-dihydroxy-5-cholen-24-oic acid antisera were prepared by immunizing rabbits with hapten-bovine serum albumin (BSA) conjugates coupled at the C-3, C-15 alpha, and C-24 positions on the bile acid molecule, and their properties were investigated by heterologous combination assay using 125I-labeled tracer. The antiserum raised against the C-3 BSA conjugate showed poor titer and specificity, while the antisera from the other two conjugates showed satisfactorily high affinity constants (Ka = 5.0 x 10(8) and 7.0 x 10(8) M-1) and reasonable specificity, exhibiting negligible cross-reactivities with other major human bile acids and cholesterol. Among the unsaturated bile acids tested, high reactivity was observed with tauro-3 beta,12 alpha-dihydroxy-5-cholen-24-oic acid, which suggested that bridge phenomena were significant in this assay system. PMID- 2598314 TI - Plasma-polymerized membrane electrode for the determination of dextromethorphan and dimemorfan. AB - Ion-selective electrodes (ISEs) responsive to the antitussives dextromethorphan and dimemorfan were constructed by the fixation of an ion-exchanger, ammonium tetraphenylborate, on a Millipore membrane by means of a plasma-polymerization technique. The electrodes showed a Nernstian response over the range of 10(-5) 10(-2) M dextromethorphan and dimemorphan, and the working pH range was 5-7. The interference from common cations such as Na+, K+ and Ca2+ was negligible but some organic cations interfered weakly. The electrodes were applied successfully for the determination of the drugs in pharmaceutical preparations. PMID- 2598315 TI - Dependence of the rate of thrombin/antithrombin III reaction upon the turnover rate of a catalytic amount of heparin. AB - Commercially available heparin preparations slightly enhanced the rate of thrombin/antithrombin (AT) III reaction at pH 6.05 in the absence of NaCl. However, this accelerative activity was significantly lower than that induced by heparin with high affinity for AT III (HA-heparin), probably due to the formation of the binary complexes of HA-heparin-AT III as well as that composed of thrombin and heparin with low affinity for AT III (LA-heparin). The HA-heparin-catalyzed thrombin/AT III reaction was faster in the presence of 0.1 M NaCl at pH 6.05 than that in the absence of the salt. LA-heparin and dextran sulfate (DS) were also found to accelerate the thrombin/AT III reaction rate, but neither substance catalyzed the formation of the complex in the presence of 0.1 M NaCl at pH 7.4. LA-heparin was also confirmed to compete with HA-heparin for enhancement of the thrombin/AT III reaction. Thus, it appears that AT III tends to form a ternary complex with the thrombin-DS or thrombin-LA-heparin complex, even in the presence of 0.1 M NaCl, whereas factor Xa reacts with the AT III-DS or AT III-LA-heparin complex. These results indicate that HA-heparin is the only substance having the ability to catalyze the thrombin/AT III reaction, and that its turnover rate is markedly elevated in the presence of strongly electropositive and electronegative ions because of the decreased affinity of the enzyme for heparin under such conditions. PMID- 2598316 TI - Oxidation of methionine residues of recombinant human interleukin 2 in aqueous solutions. AB - When recombinant human interleukin 2 (rIL-2) was stored for a long period in aqueous solutions, its methionine residues were spontaneously oxidized to the corresponding methionine sulfoxides. To clarify the oxidation process, rIL-2 was treated with hydrogen peroxide, and three oxidation products were separated by reversed-phase high-performance liquid chromatography. By means of amino acid analyses after cyanogen bromide cleavage of these products, we found that Met104, Met23, and Met39 were consecutively oxidized in this order; Met46 was not oxidized easily. The substances generated by extended storage of rIL-2 in aqueous solutions were identified by comparison of their peptide maps with those of the chemically oxidized products. The protein-chemical properties of these products, except for the modifications of the methionine residues, were similar to those of intact rIL-2; their biological activities were almost the same. PMID- 2598318 TI - Studies on chemical modification of Tulipa gesneriana lectin. AB - Modification of lysine, tyrosine, histidine, aspartic acid and glutamic acid residues did not affect the agglutinating activity of the Tulipa gesneriana lectin (TGL). Modification of two arginine residues per subunit in the lectin with either 2,3-butanedione or phenylglyoxal led to an almost complete loss of activity. An inactive lectin modified with 2,3-butanedione recovered a full activity on dialysis against Tris-HCl buffer. The presence of 0.1 M (alpha-1--- 6) linked mannotriose, a potent inhibitor of the lectin, protected all the arginine residues from modification and the lectin was fully active. Circular dichroism spectroscopy showed that no significant conformational change of TGL occurred following arginine modification. A treatment of the lectin solution with N-bromosuccinimide or 2-hydroxy-5-nitrobenzyl bromide, chemical reagents for tryptophan modification, caused turbidity of the solution, accompanied with complete loss of activity. The fluorescence emission spectrum of the lectin showed a characteristic tryptophan emission with a maximum centered at 336 nm. Upon addition of manno-oligosaccharides a decrease of the fluorescence intensity was observed, indicating that the environment of tryptophan residues altered. These results suggest that arginine and tryptophan residues are importantly involved in the sugar binding of TGL. PMID- 2598317 TI - Changes in the fluorescence characteristics of N-(1-pyrene) maleimide bound to the intestinal brush-border membranes by neuraminidase treatment. AB - The effects of neuraminidase treatment on the dynamic properties of the porcine intestinal brush-border membranes have been examined by using a fluorogenic thiol reagent, N-(1-pyrene)maleimide (NPM). Desialylation of the membranes by treatment with neuraminidase resulted in changes in the fluorescence parameters of NPM labeled membranes, i.e. a decrease of the fluorescence lifetime and a suppression of the temperature-dependent decrease of the fluorescence intensity. These results suggest that the environmental properties around NPM-labeled SH groups in the membrane proteins were modified by neuraminidase treatment. Perturbation of the microenvironment around NPM-labeled SH groups associated with desialylation by the enzyme treatment was also determined by measuring the increase of fluorescence anisotropy and decrease of quenching efficiency with acrylamide or CH3COOTl of the complex. Based on the results, it is suggested that the dynamic properties of the conformation around NPM-labeled SH groups in the membrane proteins are sensitively influenced by neuraminidase treatment. PMID- 2598319 TI - Separation of the hot water extracts of sclerotia of Sclerotinia sclerotiorum IFO 9395 into mitogenic and antitumor-active subfractions. AB - The hot water extract of sclerotia of Sclerotinia sclerotiorum IFO 9395 (TSHW) was divided into representative fractions by ammonium sulfate and ethanol precipitations, and (1----3)-beta-D-glucanase treatment. The ammonium sulfate and ethanol precipitations gave a (1----3)-beta-D-glucan fraction (TSG) and a mannan fraction (TSM). After the degradation of (1----3)-beta-D-glucan in TSHW by (1--- 3)-beta-D-glucanase treatment, a water-insoluble protein fraction (EDP) and supernatant (EDS) were obtained. Among these fractions, the mitogenic and antitumor activities were mainly observed in EDP and TSG, respectively. On the other hand, the stimulatory effect on the reticuloendothelial system was mainly found in EDP and EDS, and a weak effect was observed in TSG. These findings suggest that the mitogenic and antitumor activities of TSHW were mainly due to the protein and (1----3)-beta-D-glucan, respectively, and that the mitogenic substance (EDP) is tightly bound to (1----3)-beta-D-glucan (TSG) in TSHW, accounting for its solubility in aqueous solution. PMID- 2598320 TI - Purification and characterization of a cytolytic protein from purple fluid of the sea hare, Dolabella auricularia. AB - A novel cytolytic factor, dolabellanin P, was purified to apparent homogeneity from the purple fluid of the sea hare, Dolabella auricularia. Purified dolabellanin P is a single polypeptide of 60 kDa. The amino acid composition and the N-terminus of the factor were also determined. This factor nonspecifically lysed all the cells tested at 50-200 ng protein/ml. Dolabellanin P caused complete cytolysis within 2 h. The factor is distinct from antineoplastic glycoproteins previously isolated from eggs (aplysianin E) or albumen gland (aplysianin A) of Aplysia kurodai in terms of certain cytolytic properties. These results suggest that dolabellanin P, found in the sea hare, a marine invertebrate, is a new cytolytic factor. PMID- 2598321 TI - Pepsinogen secretion from cultured rat gastric mucosal cells. AB - Rat gastric mucosal cells were isolated with the aid of 0.1% collagenase and Dispase. Pepsinogen secretion from these cells was stimulated by carbachol, cholecystokinin octapeptide (CCK(S)-8) and pentagastrin, but not by histamine. Attempts to obtain a sufficient number of cells using a higher concentration of Dispase resulted in disappearance of the responses to secretagogues. However, when gastric mucosal cells thus prepared were cultured for 24 h in a CO2 incubator, they were found to respond not only to carbachol, CCK(S)-8 and pentagastrin, but also to histamine, resulting in an increase in pepsinogen secretion. The secretagogue-induced pepsinogen secretion was inhibited by its antagonist in a dose-dependent manner. These results suggest that the receptor present in chief cells for pepsinogen secretion was destroyed during the isolation procedure and regenerated during culture. PMID- 2598322 TI - Studies on sialic acids. XIII. Isolation of 3-deoxy-D-glycero-D-galacto-2 nonulopyranosonic acid (KDN) from chum salmon, Oncorhynchus keta. AB - A method for analysis of 3-deoxy-D-glycero-D-galacto-2-nonulopyranosonic acid (KDN) by high-performance liquid chromatography (HPLC) with a strongly basic anion-exchange resin was developed. The method was applied to detect free KDN in water used to rinse of fertilized eggs of chum salmon, Oncorhynchus keta. Furthermore, KDN was isolated from the water as a fully protected derivative. PMID- 2598324 TI - Nuclear magnetic resonance studies of cytochalasin E and its decomposition product. AB - The proton and carbon-13 nuclear magnetic resonance signals of cytochalasin E (1) were assigned with the aid of 1H-1H, 1H-13C and 1H-13C long-range chemical shift correlation spectroscopy spectra, and the structure of the decomposition product (2) generated under neutral conditions was determined. PMID- 2598323 TI - Amino acids and peptides. XXV. Application of newly developed beta-1- and beta-2 adamantylaspartates to peptide synthesis by solid phase and conventional solution methods. AB - Newly developed beta-1- and beta-2-adamantylaspartates [H-Asp(O-1-Ada)-OH and H Asp(O-2-Ada)-OH] were applied to the synthesis of a C-terminal octapeptide of the beta-subunit of human chorionic gonadotropin (hCG) by a conventional solution method and a hexacosapeptide of the alpha-subunit of insulin receptor (30-55) by a solid-phase method with the objective of suppressing aspartimide formation during the synthesis of aspartylpeptides. The 1-Ada and 2-Ada groups were confirmed to be useful protecting groups for the beta-carboxyl function of the Asp residue. PMID- 2598325 TI - Synthesis and biological activities of optical isomers of 2-(4-diphenylmethyl-1 piperazinyl)ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5 pyridinedicarboxylate (manidipine) dihydrochloride. AB - Enantiomeric (+)- and (-)-manidipine (1) dihydrochlorides were synthesized by the esterification of the optically active monocarboxylic acids (-)-6 and (+)-6, respectively. The absolute configurations, (S)-(+)-1 and (R)-(-)-1, were unambiguously determined by X-ray crystallographic analysis of (+)-7 derived from (-)-6. The (S)-(+)-1 was about 30 and 80 times as potent as the (R)-(-)-isomer in antihypertensive activity in spontaneously hypertensive rats (SHR), and in the radioligand binding assay using [3H]nitrendipine, respectively. PMID- 2598326 TI - Study on the constituents of Desmodium styracifolium. AB - Two triterpenoid saponins (1 and 2) were isolated from Desmodii Herba [the dried whole plants of Desmodium styracifolium (Osbeck) Merr. (Leguminosae)] and their chemical structures were characterized as soyasaponin I and a new saponin, 3-O [alpha-L-rhamnopyranosyl-(1----2)-beta-D-galactopyranosyl- (1----2)-beta-D glucuronopyranosyl]soyasapogenol E, respectively, by chemical and spectroscopic means. PMID- 2598327 TI - Chemical constituents of pericarps of Rosa davurica Pall., a traditional Chinese medicine. AB - From pericarps of Rosa davurica (Rosaceae), a traditional Chinese medicine, eight known tetracyclic triterpene acids, three known flavonoids, ethyl beta fructopyranoside and methyl 3-O-beta-glucopyranosyl-gallate were isolated. PMID- 2598328 TI - Saponins from leaves of Kalopanax pictum var. maximowiczii, a Korean medicinal plant. AB - From leaves of Kalopanax pictum var. maximowiczii, a Korean medicinal plant, six known saponins of hederagenin were isolated. One of the monodesmosides was identified as sapindoside A, previously isolated from Sapindus spp. Another monodesmoside and four bisdesmosides were proved to be identical with saponins K3, -K10 and -K12 and Kizuta saponins-K8 and -K11, respectively, all of which have been isolated from Hedera rhombea. It was observed that the water solubilities of these monodesmosides were increased in the presence of the co occurring bisdesmosides. The relationship between structure and solubilizing effect is reported. PMID- 2598329 TI - Hematological studies on naturally occurring substances. II. Effects of animal crude drugs on blood coagulation and fibrinolysis systems. AB - The effects of 112 extracts prepared from 37 kinds of animal crude drugs and a dog's filaria were investigated on the blood coagulation and fibrinolysis systems in vitro. The plasma recalcification time method was employed for the assay of blood coagulation and fibrinolytic activity was tested by the fibrin plate method. It was found that the water extracts of Bombyx Batryticatus, Carpio Fel and Holotrichiae Vermiculus showed potent inhibitory effects on blood coagulation. The methanol extracts of Phocae Thstis et Penis, Scorpion and Tabanus were promotive effect, on the other hand. As regards the fibrinolysis system, the water extracts of Agkistrodon, Lumbricus, Hirudo, Scolopendra and Scorpion and the methanol extract of Hirudo showed a remarkable activity. PMID- 2598331 TI - Enhancement of the dissolution rates of poorly water-soluble drugs by water soluble gelatin. AB - The dissolution behavior of several acidic and basic drugs from kneaded mixtures with water-soluble gelatin have been studied in comparison with that of the drug alone. The results revealed a significant increase of dissolution rate of drugs from kneaded mixtures. The water-soluble gelatin showed little interaction with any of the drugs in solution or in the solid state. Interestingly, the contact angle of the kneaded mixture was remarkably decreased compared with that of the drug powder and was found to be almost the same as that of water-soluble gelatin powder. Thus, the enhanced dissolution rate of the drug caused by water-soluble gelatin was explained by the improvement of wettability of the drug by water. PMID- 2598330 TI - Synthesis of macromolecular prodrugs of procaine, histamine and isoniazid. AB - The attachment of various drugs bearing -NH2 groups to poly-alpha,beta-aspartic acid as a biodegradable carrier afforded in good yields macromolecular prodrugs which were characterized with respect to composition and drug load by spectroscopic and analytical methods. N-Ethyl-N'-(3 dimethylaminopropyl)carbodiimide hydrochloride (EDC) in an aqueous medium proved to be useful in the attachment reaction. Isoniazid, procaine and histamine were covalently coupled as pendant groups onto poly-alpha,beta-aspartic acid via an amide bond. In principle, controlled release of the aforementioned drugs can be achieved by biodegradation of the polymer or by cleavage of covalently bound polymer-drug conjugates. PMID- 2598332 TI - Synthesis and antileukemic activity of (+-)-20-deoxyaminocamptothecin analogues. AB - The camptothecin analogues (+-)-7-ethyl-10-methoxy-20-deoxyaminocamptothecin (2) and (+-)-7-ethyl-10-hydroxy-20-deoxyaminocamptothecin.HCl (3) were synthesized from indolizine compound 4 via Friedlander condensation to construct a pentacyclic ring system, and were tested in a P388 mouse antileukemia assay. Compounds 2 and 3 were more active and less toxic than (+)-camptothecin (1), and therefore had higher therapeutic ratios. PMID- 2598333 TI - Syntheses of biologically active sialosylglycerol derivatives. AB - New sialosylglycerol derivatives were synthesized and found to inhibit the phospholipase A2 and C activities. PMID- 2598335 TI - [Nursing care of pulmonary heart disease during a critical attack]. PMID- 2598334 TI - [Nursing care in hepatitis treated with anisodamine (654-2)]. PMID- 2598336 TI - [Bone marrow transplantation treated in total environmental protection]. PMID- 2598337 TI - [A study of postpartum hemorrhage]. PMID- 2598338 TI - [Monitoring of hypothermia during pediatric surgery]. PMID- 2598340 TI - [Scientific management of outpatient departments and emergency clinics]. PMID- 2598339 TI - [Nursing care of the patient with hepatitis B with psychological depression]. PMID- 2598341 TI - [Use of an encouraging method in nursing management]. PMID- 2598343 TI - [Pre- and post operative nursing care in carotid body tumor surgery]. PMID- 2598342 TI - [Monitoring of selective coronary angiography and the nursing care of arrhythmia]. PMID- 2598344 TI - [The role of the nurse in the operating room during carotid body tumor resection]. PMID- 2598345 TI - [Cold dysmenorrhea with blood stagnation treated with zhuyu wengong decoction]. AB - Sixty-six women with stagnant blood and cold dysmenorrhea were treated with Zhuyu Wengong Decoction (ZWD). The results showed that 47 of them were cured, 13 improved, the total effective rate was 90.9%. Before treatment, the value of amplitude and the volume of blood flow in the left pelvic cavity with blood flow graph was very lower in the dysmenorrhea patients than those in the normal women (P less than 0.01), while the number of amplitude difference between the left and the right pelvic cavity being over 30% and of abnormal wave was higher in the patients than that in the normal women (P less than 0.01). After treatment, the value of amplitude and the volume of blood flow in the left pelvic cavity had a marked increase (P less than 0.01). These data suggested that blood circulation in the pelvic cavity took a turn for the better after the treatment. The results in animal experiment also showed that ZWD had strongly suppressive effect on the automatic action of uterine muscle of rats in vitro and of rabbits in vivo. The suppressive rates were 30.75% and 20% respectively, and the contractive range was at a lower level. The decoction also had strong suppressive effect on the contract induced by MPGF2 alpha, suppressive rate decreased to 24.4% and 34.75% respectively in contrast to the group which patients had not taken this decoction. The results in this study also proved that ZWD could improve the reduction of blood flow volume induced by MPGF2 alpha and had analgesic effect on dysmenorrhea model of rats induced by oxytocin. PMID- 2598346 TI - [Clinical effects and experimental study on gossypol in endometriosis]. AB - Effects of the gossypol on endometriosis in 12 cases of control were observed. The results showed that the gossypol administered orally was effective in endometriosis patients. The basal body temperature changed from biophase to monophase. Dysmenorrhea disappeared in 11/12 patients. Amenorrhea occurred in 10/12 patients and the ovarian endometrial cyst was shrinkable. Serum progesterone and estradiol were decreased after gossypol administration, but follicle-stimulating hormone and luteinizing hormone were increased evidently. Histochemical and cytochemical observations revealed that the activity of acid phosphate (ACP), nonspecific esterase (NSE) and alkaline phosphate (AKP) in both aberrant uterine endometrium and uterine endometrium in situ were decreased evidently. The above results suggest that the satisfactory therapeutic effect of gossypol on endometriosis may be due to not only the indirect but also the direct action on uterine endometrium. PMID- 2598347 TI - [Clinical and laboratory studies of the effect of an antilupus pill on systemic lupus erythematosus]. AB - An effort was made to get a clear understanding of antilupus pill (ALP) action on systemic lupus erythematosus (SLE) and to evaluate its therapeutic effect. ALP was originated from a notable efficacious recipe by an expert physician of TCM. It was prepared with the decoction of 17 Chinese medical herbs (such as Flos Lonicerae, Salvia miltiorrhiza etc.) to dispell noxious heat from blood, replenish the vital essence, invigorate blood circulation and resolve the stagnation. The effective rate of 92% for 230 SLE patients treated with ALP and corticosteroids, 85% for 76 patients treated with ALP alone, 79-89% for rash, trichomadesis, oral or nasal pharynx ulcer patients, and arthritis patients without deformation were obtained. The ANA titer was decreased markedly for 75% patients. ALP had no side effect and could take the part place of hormone in dosage and lessen its side effect. Through pharmacological verification it was concluded that ALP could inhibit the inflammatory process from various causes including type I, III and IV hypersensitivity, and show no response on both sensitizing and reactive stages of immunological reaction. PMID- 2598348 TI - [Prevention and treatment of recurrent urinary tract infection with a yishenkang granule]. AB - In this study, 35 female adult patients who were married and suffered from recurrent urinary tract infection in remission stage with the type of the deficiency of Kidney-Qi ( ) were admitted as the objects for this study. Before and after treatment, the T lymphocyte subtype of peripheral blood (OKT3, OKT4, OKT8), serum immunoglobulins (IgG, IgA, IgM, IgD), urinary sIg (sIgA) were performed by the ways of monoclonal antibody technique and radio-immunity analysis. The results proved that disturbances of cell mediated immunity, humoral immunity and local immune function were involved in the pathogenesis of the disease. These changes might be one of the susceptible factors that caused the repeated attacks of the disease, and the internal pathological basis of Kidney-Qi deficiency type. After taking Yishenkang granule according to the principle of benefiting Qi and invigorating the Kidney, the patients had been restored fairly from the disease on the low levels of the immune function, and strengthened on anti-infectious ability. From these, the attacks of the disease had been controlled effectively. The curative rate had reached 68.6%. PMID- 2598349 TI - [Treatment of ulcerative colitis by traditional Chinese medicine and dynamic study of immune functions]. AB - The effect of the traditional Chinese medicinal herbs enema and enteric-coated capsules in the treatment of ulcerative colitis (UC) were compared in 260 cases. The immune complexes and the dynamic change of autoantibodies were monitored in 28 out of the 260 cases before and after treatment. The following results were observed. (1) There was no significant difference in the total effective rate between the enema group and the oral capsule group (93.3% and 87.5% respectively), but the recovery rates of purulent hemafecia, mucusfecia and erosion accompanying colitis, etc. in the former group were higher than those in the latter (P less than 0.01). (2) The circulating immune complexes were found 43 times above the normal range in 17 cases with positive rate 60.7%, and tended to decrease as the condition became better after treatment. Antinuclear antibodies were determined by the indirect fluorescent immune method and the indirect enzyme labelling method and the positive rates were 53.6% and 64.7% respectively, both being much higher than those in the controls (P less than 0.01). PMID- 2598350 TI - [Pregnancy and embryotoxicity of Rhizoma pinelliae in rats]. AB - This experiment was conducted with sexually mature, virgin female rats. The body weight of the female rats was 230-350 g, that of male rats was 300-400 g. The female and male rats were mated overnight (the ratio was 3:1), the pregnant rats were divided into 7 groups. All drugs were given p.o. from the 6th to the 15th days of gestation. Pregnant rats were weighted on the 0th, 6th, 10th, 13th and 16th days of gestation. Vaginal bleeding of pregnant rats was examined on the 8th, 10th, 12th, 14th and 16th days of gestation. The rats were killed on the 20th day of gestation so as to count the number of implantation, dead and living fetuses. The living fetuses of rats were removes, weighted and inspected for gross abnormalities; the internal and skeletal malformations of live fetuses were examined. The following results were obtained: 9 g/kg dose of the crude Rhizoma Pinelliae powder was found to have the action in increasing the number of pregnant individuals with vaginal bleeding and dead embryo significantly. Comparing with the control, 9 g/kg dose of the powder of processed Rhizoma Pinelliae did not show any toxicity. But 30 g/kg dose of the decoction of processed or crude Rhizoma Pinelliae was found to increase the number of pregnant individuals with vaginal bleeding and dead embryo significantly. PMID- 2598351 TI - [Preventive action of shen mai san on heatstroke in aged rats]. AB - 15-18 month-old Wistar rats were selected and placed in 41 degrees C chamber for 12 hours. 10% Shen Mai San granule was poured into the stomachs every 3 hours. The preventive effects of this drug on heatstroke were observed. The result showed that the mortality of animal was decreased, the exhaustions of myocardial creatine phosphate and cAMP contents were significantly mitigated. By the view point of western medicine, the mechanisms recorded in traditional Chinese medicine about the preventive actions of this drug on heatstroke were also discussed in this study. The authors considered that the effects of Shen Mai San on "strengthening pulmonary Qi", "strengthening Heart Qi", might be concerned in its efficiency to stabilize the energy store in myocardium, and it might be beneficial to prevent the elderly from heatstroke. PMID- 2598352 TI - [Regulative effects of qixue injection on rhythmic activities in pacemaker cells of the sinoatrial node]. AB - This study investigated, with microelectrode technic, the effects of electrical activities in pacemaker cells of sinoatrial node by Qixue injection consisting of Ginseng, Astragali and Angelicae sinensis, which may replenish the Qi and invigorate the circulation of blood. Qixue injection produced a negative chronotropic action on beating of sinoatrial node mainly because of lowering the rate of diastolic automatic depolarization and lengthening the duration of diastolic depolarization as well, but this action was caused through neither cholinergic M receptors nor adrenergic beta receptors. With hypoxia at temperature of 41 degrees C or with isoprenaline in existence to cause beating slowness and arrhythmia, Qixue injection turned them into rhythmical beating and quickened automatic beating frequency. It suggested that Qixue injection could antagonize pathologic changes caused by insufficiency of oxygen supply and improve function of sinoatrial node. Also it indicated that Qixue injection had a biphasic function on regulating rhythmical activities of sinoatrial node, which might be one of the mechanisms of the drug used clinically. PMID- 2598353 TI - [Effect of radix Paeoniae rubra 801 on the induction of cardiac and hepatic microsomal carboxylesterases activities in male rats]. AB - Cardiac and hepatic microsomal carboxylesterases (EC. 3.1.1.1, CEase) activities were showed by measuring the released P-nitrophenol resulting from hydrolysis of P-nitrophenylacetate. Induction effects of inducers, such as PB, DEX, CPIB and Radix Paeoniae Rubra 801 (RPR 801), Radix Polygoni Multiflori (RPM), Herba Artemisiae Scopariae (HAS) on cardiac and hepatic CEase activities were observed. In the study, RPR 801 and HAS just like PB, DEX, CPIB had the induction effect on hepatic CEase activity (P less than 0.05); the liver weight could be increased by PB, DEX and CPIB (P less than 0.05) and could not be affected by RPR 801 and HAS, RPR 801 just like DEX, CPIB had the induction effect on cardiac CEase activity (P less than 0.05). The results suggested that RPR 801 and HAS could promote the hydrolysis process in liver and help to excrete of toxic substance. PMID- 2598354 TI - [Experimental study on the anti-hepatitis B virus effect of the ordinary anti hepatitis Chinese medicinal herbs]. PMID- 2598355 TI - [Recent advances in studies on tonics in Chinese herbal medicine in China]. PMID- 2598356 TI - [Therapeutic research on kidney-tonifying herbs on the adrenocortical function in the aged]. AB - The authors have observed the aging change of the adrenocortical function and the effect of the Kidney-tonifying herbs on such a change. The result showed that there was no statistical difference in the plasma cortisol levels between the aged and the young persons, and so was in the plasma corticosterone levels between the aged and the young rats. As the circulating steroids level depends on the balance of the secretion ability of the adrenal cortex and the peripheral degradation rate of the hormone, the authors measured the corticosterone concentration of the culture solution of the adrenocortical cells in vitro of the rats with different age to observe the secretion ability of the adrenocortical cell exclusively. The result showed that the corticosterone concentration was significantly lower in the culture solution of the adrenocortical cell of the aged rats than that of the young rats, which suggests that the secretion ability of the adrenal cortex declines with aging. In addition, the authors determined the reserve power of the adrenal cortex with different age and found that the increased multiple of the salivary cortisol concentration 60 minutes after the stimulation of ACTH analogue was markedly lower in the aged persons than that in the young persons. The response of the cultured adrenocortical cells to secret corticosterone to the stimulation of ACTH analogue was also significantly lower in the aged rats than that in the young rats, which suggests that the reserve power of the adrenal cortex was also decreased with aging.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598357 TI - [Clinical study on hemodynamics, blood gases and hemorheologic monitoring of patients with cor pulmonale]. AB - 14 patients of cor pulmonale in convalescent stage were studied with Swan-ganze catheter technique. The pulmonary arterial pressure, cardiac output, arterial blood gases, transcutaneous gases tension and hemorrheologic measurement were monitored simultaneously at definite intervals within 24 hours. The results showed that the mean value of the pulmonary arterial pressure (MPAP), arterial carbon dioxide tension (PaCO2), transcutaneous carbon dioxide tension (tcPCO2), hematocrit(H), whole blood viscosity (eta b) and plasma viscosity (eta p) were higher at night than those at daytime. While the value of cardiac output (CO), arterial oxygen tension (PaO2) and transcutaneous oxygen tension (tcPO2) showed a converse result, most of them showed more predominant at daytime and tended to be lowered at night. The MPAP in some of convalescent patients might decrease to normal, but in the pulmonary hypertension group [MPAP greater than or equal to 2.66 Kpa (20 mmHg)] the day and night measurements of MPAP, CO, PaO2, PaCO2, tcPO2, tcPCO2 were fluctuate more obviously than in normal group (P less than 0.01). The day and night hemorrheologic measurements such as H, eta b, eta p etc. showed that the blood viscosity increased more significantly at night than at daytime. The cardiac output (CO, CI) seemed to be a little bit lower in some patients especially in those with high pulmonary arterial pressure and at night. These results suggest that the variation of the day and night measurements of hemodynamics, blood gas, hemorrheologic changes have some rule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598358 TI - [Clinical and experimental studies of yiqi huoxue principles in treating ulcerative colitis]. AB - Yiqi Huoxue principle (YH) was applied to treat 30 cases of ulcerative colitis while Yiqi Jianpi ( ) and Qingre Qushi ( ) principle (YJQQ), which had been proved its therapeutic effect, was used as the control therapy. The herbal medicines were taken by oral and enema. The course of treatment was 6 weeks. The length, wet and dry weights of thrombus, the platelet adherence and the r, k, Ma, M values of thrombelastogram were measured before and after medications. Before medication, the value mentioned above were all abnormal in both YH and YJQQ group. After medication, with alleviation of the symptoms and signs of the colitis, all these values trend gradually to normal levels (P less than 0.01). The rat models of ulcerative colitis were made by immunological and local stimulation methods. The models were divided into three groups: YH(I), YJQQ(II) and water group(III). Three weeks after medication, the results showed that the lesion degree of the colon, the length and weight both wet and dry thrombus were remarkably lower in group I than those in group III. It was also showed that there was a positive correlation between the lesion degree of colon and the dry weight of thrombus (r = 0.7941, P less than 0.01). It suggested that the therapeutic effects of YH was similar to those of YJQQ in treating ulcerative colitis. PMID- 2598359 TI - [Clinical and experimental study on the prescription of jianpi yipi]. AB - According to "Spleen-Stomach" theory, the effect of Jianpi Yiqi prescription (JPYQ) was observed clinically and studied experimentally. 168 cases manifested as Spleen-Qi ( ) deficiency including chronic gastritis and peptic ulcer (84 cases), chronic glomerulonephritis (44 cases) and vomitus gravidarum-edema of pregnancy (40 cases) were treated with JPYQ. Estimation were made based on their clinical conditions. Serum gastrin, serum cholyglycine, blood acetylcholine and cholinesterase, blood 5-HT and histamine were measured before and after treatment. The overall effective rate was 92.9% in gastritis and peptic ulcer group, 86.3% in nephritis group and 100% in pregnancy group respectively. A marked increase of serum glycocholic acid level was shown in gastritis and peptic ulcer and vomitus gravidarum groups. That was considered as the result of the secretion of cholic acid by this prescription. Clinical improvement was also obtained in nephritis group accompanying disappearance of albuminuria in 36.4%. Blood level of 5-HT and histamine lowered to some extent and tended to be normal. Besides, this prescription markedly inhibited electric stimulated excitement on isolated longitudinal muscle strip of guinea pig's ileum. The mechanism could be the inhibition of release of acetylcholine from Auerbach's plexus by this prescription. PMID- 2598360 TI - [Antiplatelet aggregation effect of Andregraphis paniculata]. AB - This article deals with the antiplatelet aggregation effect of Andregraphis paniculata (AP), 61 blood samples and 8 volunteers were investigated to observe the effect of AP on platelet function in vitro and in vivo respectively. The results showed that the crude extract of AP could inhibit significantly one-phase and two-phase platelet aggregation induced by ADP (P less than 0.001, 0.01). The potency of AP crude extract seemed to be somewhat stronger than Ligustrazine and Persantin injection in vitro, but the difference was not statistically significant (P greater than 0.05). A dose-effect relationship of AP was demonstrated also (r = 0.93). The rapid effect of this drug on platelet aggregation in vivo suggested that AP could be absorbed quickly, but the effect lasted for only a short time. 12 hours after with-drawing of AP, the 1 minute and 5 minutes aggregation rates increased by 18.67%, 36.63% respectively, as compared with the lowest aggregation rate after administration. The activating effect of AP on fibrinolysis was also detected by shortened euglobulinlysis time (211.50 vs 182.50 min in vitro, 219.38 vs 149.38 min in vivo, P less than 0.001). In addition, the influence of AP upon coagulation and thrombelastogram was determined. This study suggested that AP in a promising antithrombogenic agent. This drug might be beneficial in preventing and treating arterial thrombotic diseases. PMID- 2598362 TI - [Experimental studies on the relation of the kidney and reproduction]. AB - To elucidate the mechanism of TCM in treating polycystic ovary syndrome, the authors tried to produce experimental PCO by sterilizing Kunming mice with 1 mg testosterone in various ages of day (5, 8, 11, 14, 17, 21 days). Every litter consisting of 10 young mice was divided into two groups: testosterone given group (T) and control group (C). At the age of 72-75 day, ovaries and uteri were weighed and all ovaries were investigated histologically. Mating was attempted in the two groups. 19 of the 20 ovaries in T5 group, but none of the other groups showed polycystic features. 4 of the 15 mice in T5 group and all of the other groups resulted in pregnancy (P less than 0.05). It was suggested that polycystic ovary was formed in the Kunming mice at age of less than 5 days administered with testosterone. For observation of tonifying Kidney drugs on the ovaries and uteri of the polycystic ovary model in Kunming mice, testosterone was given to Kunming mice of various age (2, 5, 8, 11, 14 days). The tonifying Kidney drugs for anovulatory menstrual disorder were separated into two parts, water soluble part(MS) and ester soluble part (ML). At the age of 56 days (8 weeks), two parts of the drug were given for 14 days to every group of the mice respectively. One day after the administration, uteri were weighed, ovaries were investigated microscopically, and mating was attempted in both groups. All uteri in mice taken water soluble drugs(MS) increased in weight (P less than 0.05), but not in the ML groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598361 TI - [Effect of buyang huanwu decoction on the antithrombotic functions of the vessel wall]. AB - The effects of Buyang Huanwu Decoction (BYHWD) on the antithrombotic functions of vessel wall were studied with human umbilical vein perfusion. It was observed that the both of Von Willebrand factor release stimulated by thrombin from the vessel walls and conversion of fibrinogen to fibrin catalyzed by thrombin were inhibited by BYHWD. There were no obvious effects of BYHWD on the thrombin adsorption to the vessel walls and the thrombin induced release of PGI2 as well as fibrinolysis inhibiting activity from the vessel walls. PMID- 2598364 TI - [Application of clinical research methods to traditional Chinese medicine]. PMID- 2598363 TI - [Effect of chang chun dan on noradrenaline levels of the brain and plasma in aged rats]. AB - In this paper, the rats were randomly divided into three groups: (1) Young (Y); (2) Aged (A); (3) Aged rats treated with Chang Chun Dan (AT) for 3 months. The level of noradrenaline (NA) in brain and plasma of three group rats had been examined by radioenzymatic assay. The changes of fluorescent intensity of NA in locus coeruleus had been observed by histochemical method. The levels of NA in hypothalamus of three groups were 162 +/- 9.93, 209 +/- 13.2, 167 +/- 11.8 ng/g wet tissues and in plasma were 1.29 +/- 0.16, 0.84 +/- 0.08, 0.96 +/- 0.08 ng/ml respectively. The results showed that the NA level of hypothalamus in AT group was lower than that of A group (P less than 0.05), and the NA level in Y group was raised markedly comparing with A group (P less than 0.01). The plasma NA level in A group was significantly lower than that in Y group (P less than 0.05). The NA level in AT group was raised a little comparing with A group. But the fluorescent intensity of NA in locus coeruleus between AT and A group was no difference. The results suggested that the changes of neurotransmitter induced by Chang Chun Dan may be basis of delaying aging effect and improving symptom of Kidney deficiency induced by aging. PMID- 2598365 TI - [A case of Von Hippel-Lindau disease: an often severe, multiorgan, hereditary phakomatosis]. PMID- 2598366 TI - [Comparative study of the visual evoked potentials and magnetic resonance imaging in multiple sclerosis]. PMID- 2598367 TI - [Orbital thrombophlebitis in rheumatoid polyarthritis]. AB - The description of a case of orbitary thrombosis leads to discuss the origin of orbitary thrombosis, and their links with Tolosa Hunt syndrome. The case which is studied is associated with beginning rheumatoid polyarthritis. PMID- 2598368 TI - [Beta therapy (strontium 90) associated with the removal of pterygium in order to avoid its recurrence]. PMID- 2598369 TI - [Epidemiology of myopia, astigmatism, anisometropia]. AB - Elements of epidemiology concerning myopia, astigmatism and anisometropia are still uncertain. Meanwhile, a certain number of means concerning the evolution presence and the importance of these ametropias can be proposed. PMID- 2598370 TI - [Keratomileusis without freezing--results with a 6-month follow-up]. AB - The authors describe the planar lamellar refractive keratoplasty without freezing and the results for six months. PMID- 2598371 TI - [The tritan plates of the Ergovision apparatus: evaluation]. AB - The two pseudoisochromatic tritan plates of the Ergovision apparatus were evaluated in 215 normal pathological subjects, by comparison with the usual clinical albums H.R.R., S.P.P. 2 and tritan album. A good specificity for tritan axis and a good correlation (according to statistical K of Cohen) with H.R.R. and S.P.P. 2 was evidenced for the plate n.1; this plate was not very influenced by age of the subjects. Conversely, the plate n.2 was in poor correlation with the 3 albums, and multiple false positive responses were evidenced, particularly in hereditary red-green dyschromatopsias and in subjects after 50 years. PMID- 2598372 TI - [Pseudoretinitis pigmentosa caused by congenital rubella (apropos of a case)]. AB - A case report of pseudo-pigmentary retinitis in congenital rubella embryopathy which was discovered in a grown-up patient who had visual field defects and unusual lesion of retinal vessels. The authors describe the principal features of congenital rubella embryopathy's retinal involvement. PMID- 2598374 TI - [Apropos of a new implant for evisceration]. PMID- 2598373 TI - [Retinal folds--diagnostic problems]. PMID- 2598375 TI - [Diffuse retinoblastoma--apropos of a case]. AB - We report a case of diffuse retinoblastoma in a 6 years old boy. The diagnosis should be suspected in front of the very evocative clinical picture itself. The aspect of the tyndall phenomenon, and of the convex pseudo-hypopyon, with iris pearls and nodules, together with a peripheral, imprecisely limited, retinal mass, non calcified on ultrasonographic examination, are typical. Aqueous paracentesis shows increased levels of Lactic Dehydrogenase (LDH), but most of all the cytologic examination confirms the diagnosis. The only treatment is enucleation. The clinical picture which may simulate uveitis, especially as this particular type of retinoblastoma has a late onset. PMID- 2598376 TI - [Aids for low vision--strategic approach]. AB - There are currently methods to rehabilitate the remaining visual function of visually impaired people. Treatment stages and tests are based on classical physiology of vision and still remain strictly experimental. Recent investigations showed that the visual system, as a whole, operates as a space frequency analyzer. There are reception to each spatial frequency. They have to be assessed with accuracy before any rehabilitation attempting to develop channels which are still functional by elective stimulation. This stimulation must have a maximum determined energetic efficiency. The study of the Fourier spectrum on two different images demonstrates this possibility and starts opening the way for specific research. PMID- 2598377 TI - [Association of a lattice dystrophy and keratoconus: anatomo-clinical study apropos of a case]. PMID- 2598378 TI - [Anatomo-clinical study of 2 lenticules in myopic epikeratoplasty]. PMID- 2598379 TI - [Oculomotor equilibrium and accommodation-convergence]. PMID- 2598381 TI - [Transfer under local anesthesia from nasal-bicanalicular intubation to annular bicanalicular intubation--apropos of 7 cases]. PMID- 2598380 TI - [Orbital Kaposi sarcoma in a subject not infected with HIV]. PMID- 2598382 TI - [Practical aspects of the evaluation of preoperative aniseikonia]. AB - Ten years ago, Dr. Simone Delthil, who was one of the first, in France, to make researches into aniseikonia, departed from this life. This anniversary offers the opportunity to the authors to recall that it is most desirable, before operating, that theoretical modifications of the size of retinian pictures should be considered, according to the selected compensatory method, especially in the case of anisometropia or unilateral aphakia. PMID- 2598383 TI - [Morning glory syndrome]. PMID- 2598384 TI - [Demonstration by brain mapping of cortical neutralization in functional amblyopia]. PMID- 2598385 TI - [6 new cases of spasmus nutans]. AB - Six new born presenting an acquired nystagmus, associated with rhythmic head movements, have been explored clinically, electrophysiologically and neuroradiologically. Etiopathogenic hypotheses and experimental models are proposed. A twenty last years literature review is mentioned. It seemed interesting to authors to practice head scanners to find an organic lesion. The ethnic incidence is not negligible. PMID- 2598386 TI - [Calculation of the implant: is it a useless luxury?]. AB - Analysis of the means by which accuracy of intraocular lens power calculation could be improved with theoretical and linear regression formulas. The postoperative refractive errors with the lenses selected by the surgeon were compared with those observed with the emmetropic calculated power lenses and with a standard 20 diopters lens. A consecutive series of 100 eyes with less than 4.50 diopters of pre-operative myopia or hypermyopia, is evaluated. Postoperative refractive errors are out of the range -4; +4 diopters in 6% for standard lens, 4% for actually implanted lens, and 1% for emmetropic power calculated lens. PMID- 2598387 TI - [Calculation of the power of implants. Analysis of 221 records]. PMID- 2598388 TI - [Prolonged mydriasis caused by Lamaline]. AB - Atropine derivatives. The presence of atropine derivatives in numerous combined medicines is often ignored or reflected. A case report of prolonged bilateral non reactive mydriasis with "cycloplegia", linked with the utilisation of a therapeutic dose of Lameline suppositories raises the question of individual susceptibility, with particular ocular sensitivity. This urge one not to ignore the presence of these products and to respect the contraindications, even with minute doses. PMID- 2598389 TI - [Treatment of lacrimal duct obstruction]. PMID- 2598390 TI - [Importance of modulated neuroleptanalgesia in anterior chamber implantation]. AB - About 192 anterior chamber implantations, the authors report the advantage to utilize modulated neuroleptanalgesia. PMID- 2598391 TI - [Diabetes and the insulin pump: functional results after 5 consecutive years of permanent use]. PMID- 2598392 TI - [Intraocular pressure during vitrectomy in diabetic patients]. AB - 23 eyes underwent vitrectomy for diabetic proliferative retinopathy complications: vitreous hemorrhage with or without tractional retinal detachment. After 6 months of follow-up, 64% of eyes had final visual acuities of 1/40 or better. Preoperative iris neovascularization and preoperative detachment of the macula have a worse prognosis. Decrease of peroperative complications is allowed by checking of intraocular pressure during vitrectomy. PMID- 2598393 TI - [Double paralysis of the superior oblique muscles caused by ventricular inundation]. PMID- 2598394 TI - [A case of ocular sarcoidosis]. PMID- 2598395 TI - [Galand disk implant and pupillary block]. AB - We have implanted 530 Galand's disc lens in the last 15 months. Stability and self-centering of implant were good when peroperative vitreous pressure was normal and in any case when wound was closed. Pupillary blocks, specific complications of this lens were rare (less than 1%); they can be prevented occurred by simple and adequate protocols. PMID- 2598396 TI - [Use of Gore-Tex in ptosis surgery for suspension from the frontal muscle]. PMID- 2598397 TI - Nephrotoxicity of 5-(N-phenylcarboxamido)-2-thiobarbituric acid in the Fischer 344 rat. AB - In the present investigation, administration of a single i.p. dose of the anticancer drug merbarone [5-(N-phenylcarboxamido)-2-thiobarbituric acid] produced an acute and reversible decrease in renal function in female but not male Fischer 344 rats. The renal lesion in female rats was biochemically characterized as a decrease in p-aminohippuric acid accumulation by renal slices along with polyuria, glucosuria, proteinuria, and enzymuria. These functional changes were accompanied by histopathologic changes of focal tubular necrosis that was confined to the deep cortex and outer stripe of the outer medulla. The changes in these parameters were dose-dependent and were observed at doses as low as 0.2 x MELD(10) (12 mg/kg). This low merbarone dose increased urinary glucose and protein excretion by 26- and 9-fold, respectively, in the initial 16-h urine collection in female rats. This increase was accompanied by a 2- to 15-fold increase in the excretion of N-acetyl-beta-D-glucosaminidase (NAG), gamma glutamyl transpeptidase (gamma-GTP), and lactate dehydrogenase (LDH) activities. No significant changes in renal function were observed in male rats apart from mild enzymuria after a high dose of merbarone (36 mg/kg). The drug did not increase urea nitrogen levels in male or female rats, reflecting the focal nature of this tubular lesion. Merbarone produced small elevations in serum transaminase activities [i.e., glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)] at doses that produced marked alterations in renal function in female rats, suggesting only mild hepatotoxicity. The present study establishes the kidney as a possible dose-limiting target organ for merbarone toxicity. PMID- 2598398 TI - Morphological change and cellular differentiation induced by cisplatin in human neuroblastoma cell lines. AB - In 1986 we reported on the capacity of cis-diaminedichloroplatinum(II) (cisplatin, CDDP) to induce erythroid cellular differentiation in the K562 cell. To continue our study of the differentiating activity of cisplatin, we treated two human neuroblastoma cell lines with different doses of the drug in vitro. Both cell lines showed changes in morphology; however, only one achieved a fully differentiated neuronal phenotype (cisplatin concentration 1 micrograms/ml). The differentiated neuroblastoma cells exhibited extensive neurite outgrowth that reached maximal elongation after 5 days of culture, forming several interconnections. Cisplatin could induce neuronal differentiation, as did retinoic acid, a neuroblastoma-differentiating agent. The results show that cisplatin should be a candidate for further in vitro and in vivo studies of induced differentiation. PMID- 2598399 TI - Phase II trial of 5-fluorouracil, adriamycin and cisplatin (FAP) followed by radiation and 5-fluorouracil in locally advanced pancreatic cancer. AB - A total of 19 patients (7 men, 12 women) with locally advanced pancreatic adenocarcinoma were treated with six cycles of FAP (5-fluorouracil, 300 mg/m2 i.v. on days 1-5; Adriamycin, 50 mg/m2 i.v. on day 1; cisplatin, 20 mg/m2 i.v. on days 1-5). Each course was repeated every 28 days. After six cycles, the treatment was followed by irradiation amounting to 4,000 cGy (split course) in combination with 5-FU (500 mg/m2) on days 1-3 of the two irradiation periods. The median age of our patients was 55 years (range, 40-64 years). The median WHO performance status was 1, with a range of 0-2. Three (16%) complete (CR) and six (31%) partial responses (PR) were observed, as were six cases of stable disease (SD) and four of progressive disease (PD). The median duration of response was 11 months, with a range of 4-24 months, and the median survival was 14 months (range, 5-27 + months). FAP toxicity was tolerated fairly poorly. The dose limiting toxic effect was myelosuppression, with a mean WBC nadir of WHO grade 1.6 (range, 0-3) and a mean platelet count of WHO grade 1.1 (range, 0-4). Nausea and vomiting were not dose-limiting. Complete alopecia was seen in 14/19 patients. Neuropathy was mild (WHO grade 1) in seven and moderate (grade 2) in four. Irradiation in combination with 5-FU was generally well tolerated. Due to several reasons, only ten patients could be treated with all six cycles of FAP. We conclude that in future combined modality studies, irradiation should be given after three cycles of chemotherapy, and that combined modality treatment for locally advanced pancreatic cancer is feasible and warrants further testing. PMID- 2598400 TI - Salvage chemotherapy of refractory non-Hodgkin's lymphoma with aclacinomycin, behenoyl ara-C, etoposide, and prednisolone. AB - A total of 40 patients with recurrent non-Hodgkin's lymphoma were treated with ABEP combination chemotherapy (aclarubicin, N4-behenoyl-1-beta-D arabinofuranosylcytosine, etoposide, and prednisolone). A complete remission (CR) was achieved in 37.5% of the patients and partial remission, in 15.0%. The ABEP regimen proved to be effective in T-cell as well as B-cell lymphoma. It appears that the ABEP regimen may be partially non-cross-resistant with front-line doxorubicin-containing combinations. Survival for 39 months was achieved in 42.0% of the CR responders compared with 6.7% of partial responders (PRs) and nonresponders (NRs) (P less than 0.01). Disease-free survival for 45 months was seen in 66% of the CR patients. The ABEP regimen was effective in the treatment of patients with recurrent or refractory lymphoma, enabling hope for long-term survival in the majority of CR cases. PMID- 2598401 TI - [131I]-metaiodobenzylguanidine in the treatment of metastatic neuroblastoma. Clinical, pharmacological and dosimetric aspects. AB - Ten children with stage III or IV neuroblastoma that had either relapsed or was refractory were treated with [131I]-metaiodobenzylguanidine (MIBG) from 1984 to 1986. The total dose ranged from 4,365 to 21,900 MBq and was given in one to five courses. Two patients achieved a complete remission (CR), two, a partial remission (PR), and three, an arrest of the disease. Pharmacological studies showed that 93% of detectable radioactivity was attributable to MIBG at the beginning of the infusion. However, by the end of the infusion this had decreased to 88%. The terminal half-life of MIBG was 37.0 h, whereas that of non-MIBG-bound iodine was 71.6 h. Therefore, the radioactivity-time product of non-MIBG-bound 131I was much higher than that of MIBG. Dosimetric studies showed a mean level of absorbed radiation for the total body of 160 microGy/MBq, a liver irradiation of 540 microGy/MBq and a mean tumour radiation of 10,500 microGy/MBq. PMID- 2598402 TI - Relationship between cytotoxicity, drug accumulation, DNA damage and repair of human ovarian cancer cells treated with doxorubicin: modulation by the tiapamil analog RO11-2933. AB - The effect of N-(3,4-dimethoxyphenyl) N-methyl-2-(naphthyl)-m-dithiane-2 propylamine hydrochloride (RO11-2933), an analog of the calcium channel blocker tiapamil, on doxorubicin (DOX)-induced cytotoxicity and DNA damage in human ovarian cancer cells sensitive and resistant to DOX was investigated. A2780-DX2, A2780-DX3, and A2780-DX6 cell sublines were characterized by 7-, 26-, and 48-fold resistance after 2 h DOX exposure and 30-, 50-, and 500-fold resistance after 72 h DOX exposure, respectively. Increased drug efflux resulting in a lower intracellular drug accumulation, decreased DOX-induced DNA single-strand breaks (DNA SSBs), and rapid DNA repair correlated with the degree of resistance. In addition, DNA SSBs were rapidly repaired within 8 h in A2780-DX3 cells, whereas no significant repair of DNA SSBs was observed in sensitive cells. In comparison with verapamil, RO11-2933 was found to reverse DOX resistance at lower and nontoxic concentrations (2 microM as compared with 10 microM verapamil). This reversion was complete in cells with a low degree of resistance (A2780-DX1 and A2780-DX2) but partial in highly resistant cells (A2780-DX3 and A2780-DX6), and continuous exposure to RO11-2933 was essential for optimal reversal of drug resistance. Interestingly, RO11-2933 was found to inhibit the repair of DNA SSBs induced by DOX but not those induced by X-ray. These results suggest that the potentiation of DNA SSBs and the specific inhibition of DNA repair by RO11-2933 in multidrug-resistant cells could be of particular value in overcoming MDR in the clinic. PMID- 2598403 TI - Evaluation of N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea against xenografts of pediatric rhabdomyosarcoma. AB - N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea (LY186641), a novel anticancer compound, was evaluated against six lines of rhabdomyosarcoma xenografts, each of which was established from tissue biopsies from untreated patients, and additional sublines selected as xenografts for primary resistance to vincristine, melphalan, and ifosfamide. LY186641 was given by oral gavage twice daily for 10 consecutive days or as 5-day courses repeated at 7-day intervals. At the optimal schedule, complete regressions of advanced tumors were obtained in each of the six rhabdomyosarcoma lines. There was no apparent cross-resistance in RMS lines selected for vincristine resistance or against multiple-drug-resistance KB cells in vitro. There was slight cross-resistance in xenografts selected for melphalan resistance, but not in an ifosfamide-resistant line. These results indicate that LY186641 may have significant clinical activity in the treatment of childhood rhabdomyosarcoma. PMID- 2598405 TI - Protection against cisplatin nephrotoxicity by prochlorperazine. AB - Prochlorperazine (Compazine; PCPZ) is often used to limit cisplatin (CDDP) induced emesis. However, recent studies in mice have shown that PCPZ protects against renal injury produced by treatment with various nephrotoxicants (e.g., MethylCCNU, mercuric chloride). Because renal toxicity remains a serious limitation to the effective use of CDDP, we conducted the present study to determine whether PCPZ could also protect against CDDP-induced renal injury. PCPZ treatment was shown to ameliorate CDDP-induced renal lesions in both rats and mice at doses and treatment schedules that were comparable with those used for alleviating chemotherapy-induced emesis. A PCPZ dose of 10 mg/kg x 2 offered complete protection against CDDP-induced increases in blood urea nitrogen (BUN) levels in mice, with significant protection occurring at a PCPZ dose as low as 5 mg/kg. Similarly, PCPZ ameliorated CDDP-induced increases in BUN, glucosouria, and enzymuria in F344 rats. PCPZ treatment did not affect the urinary excretion or renal tissue levels of total platinum or the plasma pharmacokinetics of free platinum. However, it did cause a marked reduction in the concentration of total plasma platinum (free platinum + protein-bound platinum). PCPZ was not found to affect the in vivo antitumor activity of CDDP against P388 leukemia. The present study suggests that PCPZ may be of therapeutic benefit when used with CDDP and provides a rational basis for the selection of antiemetic therapy. PMID- 2598404 TI - In vitro evaluation of cisplatin interaction with doxorubicin or 4 hydroperoxycyclophosphamide against human gynecologic cancer cell lines. AB - Doxorubicin, cisplatin, and cyclophosphamide are the three drugs most commonly used in the treatment of ovarian cancer, but no effect greater than additivity was observed for any combination of these drugs in the present study. Only a few studies have been reported concerning the degree of their additivity or their best order of sequencing. In our in vitro studies, cisplatin in combination with doxorubicin or 4-hydroperoxycyclophosphamide (4HC) was tested against seven human gynecologic tumor-cell lines in different sequences, using a double-agar layer tissue-culture system. Drug interactions with respect to inhibition of tumor clonogenicity were evaluated by isobologram and fractional survival methods. Doxorubicin and 4HC were sequenced simultaneously and at 1, 6 and 24 h after cisplatin, and cisplatin was sequenced at 1, 6 and 24 h after 4HC. The isobolograms constructed for doxorubicin or 4HC plus cisplatin revealed strict additivity between these agents against ovarian cancer clonogenicity. Both doxorubicin and 4HC showed the greatest additivity when used simultaneously and at 1 h vs 6 or 24 h after cisplatin. Although the mechanisms by which these sequencing effects occur are unknown, these studies provide new leads for the design of clinical trials with combinations of these three agents. PMID- 2598406 TI - Pharmacologic basis for the use of dipyridamole to increase the selectivity of intraperitoneally delivered methotrexate. AB - Dipyridamole (DP) is an attractive agent with which to increase the selectivity of intraperitoneally delivered methotrexate (MTX). We demonstrated that DP synergistically increased the cytotoxicity of MTX to the human OV 2008 ovarian carcinoma cell line in vitro and that this synergy was highly concentration dependent. DP did not alter MTX binding in plasma, and vice versa. We found that the two drugs were chemically compatible at concentrations of less than 400 microM, which was well above the concentration needed to make continuous i.p. infusion feasible. The ability of OV 2008 cells to accumulate uridine was used as a bioassay for the in vivo activity of DP. When this drug was infused i.p. at 12 mg/m2 per day, the steady-state peritoneal DP concentrations attained in patients were sufficient for maximal inhibition of uridine uptake, indicating concentrations high enough for synergism with MTX. We found no correlation between total peritoneal protein concentration and either free DP concentration or biologic activity. On the basis of these preclinical and pharmacologic measurements, we conclude that it should be possible to produce selective i.p. biochemical modulation of MTX with DP. PMID- 2598407 TI - Synergy between 5,10-dideaza-5,6,7,8-tetrahydrofolic acid and methotrexate in mice bearing L1210 tumors. AB - In vivo studies with 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), an inhibitor of glycinamide ribonucleotide transformylase, indicate that at doses ranging from 2.5 to 10 mg/kg, it prolongs the survival of mice implanted with L1210 tumors. Lower doses of this agent have no effect. Parallel studies with methotrexate indicate that DDATHF is not as potent or as efficacious as methotrexate in this animal model. Low doses of DDATHF combined with low doses of methotrexate can cause a significant increase in the survival of L1210 tumor bearing mice, suggesting synergism between these two antifolates. PMID- 2598408 TI - Comparative uptake and retention of adriamycin and N-benzyladriamycin-14-valerate in human CEM leukemic lymphocyte cell cultures. AB - N-Benzyladriamycin-14-valerate (AD 198) is a new lipophilic adriamycin (ADR) analogue that shows marked therapeutic superiority to ADR in murine tumor model systems yet differs mechanistically from ADR in a number of ways. Among its other properties, AD 198 produces a delayed but profound effect on cell-cycle progression and a pattern of continuing DNA damage in cultured cells briefly exposed to the drug. Using radiolabeled drug forms and radioassays combined with HPLC separation and fluorimetric detection techniques, aspects of drug accumulation, biotransformation, and retention in cultured human CEM leukemic lymphocytes were studied, in part to determine a possible pharmacologic basis for the latent effects seen with this drug. In addition, the cellular pharmacology of AD 198 and ADR were comparatively examined under identical experimental conditions. When CEM cells were incubated with drug at equi-growth inhibitory/minimally cytotoxic concentrations (AD 198, 1.0 microM; ADR, 0.1 microM), a number of differences were apparent. Under conditions of continuous 24 h drug exposure, a slow cellular accumulation and equilibration was observed with ADR (cell: medium equilibrium, 1:11 after 4-6 h), whereas the uptake of AD 198 was rapid and extensive (cell: medium equilibrium, 3:1 within 30 min). In drug retention studies, when cells were pretreated at the same drug concentrations as before (AD 198 for 1 h; ADR for 4 h) and then transferred to drug-free media, both compounds re-equilibrated their intracellular drug content with the fresh media, losing about 50% of their respective anthracycline levels. Liquid chromatographic analysis of ADR-treated cultures under both sets of conditions showed the parent drug to be the only intracellular anthracycline species, whereas analysis of AD 198-treated cultures revealed two fluorescent signals corresponding to the parent drug and its 14-de-esterified biotransformation product, N-benzyladriamycin (AD 288). Levels of AD 288 rose from 2% of the total intracellular anthracycline content immediately on drug admixture to 61% following 24 h continuous drug exposure and to 69% at 24 h in cells exposed to drug for 1 h and then continued in drug-free media for 24 h. At all times, the balance of the intracellular anthracycline fluorescence was attributable to the parent drug; no ADR was detectable in AD 198-treated cells by either fluorescence detection or radioassay.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2598409 TI - Isolation, identification and biological activity of a phyllanthoside metabolite produced in vitro by mouse plasma. AB - The antitumor agent phyllanthoside is rapidly metabolized in vitro by mouse plasma. This metabolite has now been isolated from mouse plasma and its structural properties and cytotoxicity characterized. The isolated metabolite was estimated to be greater than 98% pure by HPLC analysis. Mass spectral analysis (fast atom bombardment and tandem mass spectrometry) indicated that the metabolite was the aglycone of phyllanthoside that resulted from the cleavage of the ester bond linking the aglycone and the disaccharide moieties of phyllanthoside. This identification was based on identical collision-induced dissociation spectra of both phyllanthoside and the metabolite. The aglycone was not formed by mouse plasma that had been boiled, filtered to remove proteins, or treated with 1.0 mM diisopropyl fluorophosphate. These results suggest that aglycone formation occurs as a result of plasma esterase activity. Michaelis Menten constants, Vmax and Km, for conversion of phyllanthoside to the aglycone at 22 degrees C were estimated to be 1.1 mmol/ml plasma/min and 2.0 mM, respectively. Concentrations of phyllanthoside and metabolite required to inhibit cell-colony formation by human A204 rhabdomyosarcoma in vitro were 0.47 nM and 24 microM, respectively. The toxicity of phyllanthoside, and perhaps its efficacy as an antitumor agent in mice, may depend on its rate of conversion to the aglycone. PMID- 2598411 TI - Validated HPLC procedures for the analysis of MBY-28090 in human plasma and urine. AB - The compound BMY-28090 (elsamicin A) is a new fermentation product with antitumor properties, which has the same aglycone as chartreusin but contains two novel sugars. To define the disposition of BMY-28090 during phase I trials, HPLC procedures were developed and validated for the quantitation of the drug in human plasma and urine. To 1.0 ml plasma were added 0.5 ml 0.2 M phosphate buffer (pH 8.0), 125 ng 1-naphthol (internal standard) in 25 microliters MeOH and 5 ml ethyl acetate. After mixing and centrifugation, 4 ml ethyl acetate layer was removed, evaporated to dryness, and the residue was dissolved in 250 microliters mobile phase and injected (200 microliters). To 1.0 ml urine were added 100 microliters MeOH and 1.0 ml 0.5 M succinate buffer (pH 4.0). After mixing (30 s) and sonication (1 min), the solution was filtered in an Amicon Centrifree micropartition unit and injected (30 microliters). An IBM C-8 column 5-microns and fluorescence detection (excitation at 254 mm, 418 nm emission filter) were used for both analyses. The mobile phases for plasma (2 ml/min) and urine (1.3 ml/min) were H2O/CH3CN (7:3 v/v) and H2O/CH3CN/MeOH (6:3:1 (v/v), respectively, with 1.5 ml 85% H3PO4 and 1.5 ml triethylamine/l. BMY-28090 eluted at 8-10 min and 1-naphthol, at 10-11 min. The standard curves were linear from 1 to 50 ng/ml plasma and from 10 to 1000 ng/ml urine. The within- and between-day precision was less than 3% for plasma and less than 5% for urine. Accuracies were within 6% of the nominal value and recoveries were 75% and 90% for plasma and urine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598410 TI - 6-ethylmercaptopurine-mediated growth inhibition of HL-60 cells in vitro irrespective of purine salvage. AB - A variety of purine analogs inhibit the growth and induce the differentiation of human promyelocytic leukemia (HL-60) cells that lack the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Mechanisms by which purine analogs induce differentiation offer unique potential for cancer chemotherapy. The guanine analogs, 6-thioguanine and 8-azaguanine, induce granulocytic differentiation of HGPRT-deficient HL-60 promyelocytes. Although these compounds are useful as model purine analogs that induce differentiation in HGPRT-deficient HL-60 cells, they suffer the disadvantage that they are highly cytotoxic to wild-type cells. We studied the effect of the hypoxanthine analog 6 ethylmercaptopurine on wild-type and HGPRT-deficient HL-60 cells. 6 Ethylmercaptopurine inhibits growth and produces a specific terminal end-cell in both types of HL-60 cells. The mechanism appears to be independent of the normal modes of cytotoxic activation through HGPRT or adenine phosphoribosyltransferase (APRT), since no new peaks were seen in HPLC chromatograms of the nucleotide pools. Furthermore, hypoxanthine and adenine failed to prevent growth inhibition by 6-ethylmercaptopurine, and inhibition of IMP dehydrogenase and the consequential alteration of the guanine nucleotide pools does not appear to be involved. The mechanism differs from that of guanine analog-induced differentiation in HGPRT-deficient HL-60 cells. PMID- 2598412 TI - Characterization of the anti-tumour activity against solid tumours of a new nitrosoureido sugar: Cy 233. AB - The anti-tumour properties of Cy 233, a new nitrosoureido sugar, were investigated in two murine solid tumours: B16 melanoma and subcutaneously implanted colon adenocarcinoma. Injected i.v., Cy 233 exerted a strong anti tumour effect against the established B16 melanoma: long-term survivors were recorded with all schedules of treatment. The drug was even more effective against advanced colon 38 adenocarcinoma: it produced a high percentage of total tumour regression, regardless of the route of administration (i.p., i.v., p.o.). The marked in vivo activity of Cy 233 against advanced colon 38 adenocarcinoma, which is known to be resistant to such major anti-cancer drugs as BCNU and chlorozotocin, its water solubility and its stability in aqueous media are further elements warranting toxicological and clinical studies of this agent. PMID- 2598414 TI - Differential expression of interleukin-1 and tumor necrosis factor in murine septic shock models. AB - Murine shock models have employed bolus endotoxin as well as cecal ligation and puncture (CLP) in an attempt to understand the pathophysiologic changes associated with human septic shock. Injection of endotoxin results in a rapid but transient rise in tumor necrosis factor (TNF), with maximal levels between 1 and 2 hr followed by an increase in serum interleukin-1 (IL-1) by 3 hr which remains elevated at 24 hr. CLP animals in contrast do not demonstrate an elevation in serum TNF, and the increase in IL-1 is less significant relative to the endotoxin model. Whereas both models demonstrate comparable increases in serum amyloid A protein and result in host death between 24 and 48 hr, these models respond differently to therapeutic modalities. Steroids and an anti-TNF monoclonal antibody administered prophylactically are effective at preventing death in the endotoxin model and yet had no beneficial effect in antibiotic-treated CLP animals. Experiments with adrenalectomized mice suggest that the absence of serum TNF in the CLP model is in part due to the modulatory effects of endogenous corticosteroids. PMID- 2598413 TI - Reduction of B16 melanoma metastases by oral administration of egg-white lysozyme. AB - The oral administration of hen egg-white lysozyme to mice bearing B16 melanoma significantly reduces the formation of spontaneous lung metastases and, when combined with surgical removal of the primary tumor, prolongs the survival of the treated hosts. The antimetastatic effect, comparable with that found in the Lewis lung carcinoma and MCa mammary carcinoma systems, is independent of the direct interaction of lysozyme with tumor cells and tends to indicate the suggested intervention of an indirect action mediated by the induction of host responses. PMID- 2598415 TI - Rat liver metabolism in hemorrhagic traumatic shock. AB - Rats were bled to a mean arterial pressure of 40 mm Hg until the onset of decompensatory shock (marked by the need to return some blood in order to maintain the blood pressure) at which time all the shed blood was returned. 31P nuclear magnetic resonance (NMR) spectra of their livers were collected during the shock and a subsequent 60 min recovery period. Adenosine triphosphate (ATP) levels fell linearly with time, in some instances to zero during shock. ATP recovery was very rapid after return of shed blood but did not return to its preshock values. Levels of ATP remained stable during the 60 min of recovery. From the rapid recovery after total depletion of ATP in this study and in other NMR studies on perfused ischemic livers, as well as the discrepancy in residual levels of ATP during shock and ischemia as measured by in vivo NMR or by extraction techniques, we argue in favor of metabolically inaccessible pools of adenine nucleotides during these hepatic stresses. PMID- 2598416 TI - Intramucosal pH measurement with tonometers for detecting gastrointestinal ischemia in porcine hemorrhagic shock. AB - Intraluminal pCO/ was measured in the stomach, small intestine, and sigmoid colon of pigs using balloon catheters (Tonomitor). With the simultaneously determined arterial blood HCO3 concentration, the intramucosal pH (pHi) could be calculated using the Henderson-Hasselbalch equation. Cardiac output and portal venous flow were measured using Swan-Ganz catheters. A series of 35 normotensive pigs were studied to achieve normal values of cardiac output, gastrointestinal pHi, and blood flow in pigs. In another series of pigs (n = 12), hemorrhage was induced in two steps and followed by retransfusion. Five additional animals served as controls. Gastric, small intestinal, and colonic pHi decreased with increasing degree of hemorrhage but remained unchanged in the controls. Following severe hemorrhage, pHi fell below the normal range in all pigs but one. It recovered only partly following retransfusion. Histological examination of specimens obtained following retransfusion revealed normal mucosa in six of eight investigated animals and superficial mucosal injury in the remainder, indicating that abnormal pHi may be found for a period in the microscopically normal gastro intestinal mucosa. Monitoring pHi in the stomach, small intestine, or colon using tonometers could be a useful technique to reveal insufficient mucosal blood flow in the alimentary canal. PMID- 2598417 TI - Aortic stenosis in elderly patients aged 80 or older. Treatment by percutaneous balloon valvuloplasty in a series of 92 cases. AB - Very elderly patients with severe aortic stenosis will probably benefit from percutaneous balloon valvuloplasty. Ninety-two patients, aged 80 or older (mean age, 84 +/- 3.7 years) and all severely incapacitated (18 with an associated pathologic condition or in critical condition with terminal heart failure), underwent a valvuloplasty procedure. Femoral access was used in all cases except seven (8%), in whom the femoral route had to be abandoned and the brachial approach was used due to severe arterial tortuosity. Peak-to-peak ventriculoaortic gradient decreased from 71 +/- 27 to 27 +/- 15 mm Hg, and the aortic valve area increased from 0.48 +/- 0.16 to 0.91 +/- 0.35 cm2 (p less than 0.01). Thirty-two percent had a postprocedure aortic valve area more than or equal to 1 cm2. The final valve area was less than or equal to 0.7 cm2 in 30% of the patients. There were three deaths (ages, 82, 92, and 98 years) in the procedure room. One stroke occurred 1 day after the procedure. Hematoma or thrombosis at the femoral puncture site was observed in 14 cases (15%), requiring surgical repair in only five cases. Three patients died in the hospital; the total in-hospital mortality was 6.5%. Among the 62 patients about whom information could be obtained at a mean follow-up interval of 13 +/- 5 months, there were 18 late deaths (mean age, 85 +/- 11 years). The majority of the surviving 44 patients experienced marked symptomatic improvement. The results indicate that balloon valvuloplasty can be offered to very elderly patients with severe aortic stenosis and can produce improvement in hemodynamic and clinical status. PMID- 2598418 TI - Assessment of left-to-right atrial shunting after percutaneous mitral valvuloplasty by transesophageal color Doppler flow-mapping. AB - To evaluate left-to-right shunts after percutaneous balloon mitral valvuloplasty, we studied 15 consecutive patients by using transesophageal color Doppler flow imaging system. Transesophageal color Doppler examinations were performed five times in each patient (before valvuloplasty and 1 day, 1 week, 1 month, and 6 months after valvuloplasty). No shunt flow was observed before valvuloplasty. On 1 day after mitral valvuloplasty, transesophageal color Doppler echocardiography demonstrated left-to-right shunts in 13 (87%) of 15 patients. However, a significant oxygen step-up was present in the right heart in only one patient. The mean diameter of the interatrial septal defect detected by transesophageal two-dimensional echocardiography was 1.8 +/- 1.0 mm. The mean velocity of left-to right shunting flow measured by high-pulse repetition frequency Doppler technique was 0.83 +/- 0.38 m/sec. One week after the procedure, left-to-right shunt flow was detected in 11 (73%) patients. One month after valvuloplasty, left-to-right shunting flow was detected in seven (47%) of 15 patients. There was a significant decrease in the diameter of an interatrial septal defect between 1 day and 1 week (p less than 0.01), between 1 week and 1 month (p less than 0.01), and between 1 month and 6 months (p less than 0.05). Six months after valvuloplasty, left-to right shunting flow remained in three (20%) patients. By using transthoracic color Doppler echocardiography, we detected left-to-right shunting flow in two patients on 1 day after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598419 TI - Catheter ablation of the atrioventricular junction with radiofrequency energy. AB - Catheter ablation of the atrioventricular junction using direct-current defibrillator discharges requires general anesthesia and may have serious side effects. Sixteen patients with drug-refractory supraventricular tachycardia underwent catheter ablation of the atrioventricular junction using radiofrequency energy. A standard 7F quadripolar electrode catheter was positioned to record the largest unipolar His potential (580 +/- 640 microV) from the distal electrode. An electrocoagulator (Microvasive Bicap 4005) supplied continuous, unmodulated energy at 550 kHz. One to 14 applications of radiofrequency current were delivered between the distal electrode and a large-diameter chest wall electrode. Transient, mild chest discomfort was reported by seven of 16 patients. None had significant arrhythmias or blood pressure changes during radiofrequency ablation. Complete atrioventricular block was produced in nine of 16 patients and high grade second-degree atrioventricular block was produced in one patient with radiofrequency current. Attenuated His bundle electrograms could still be recorded in the remaining six patients, four of whom underwent successful atrioventricular junctional ablation using direct-current shock during the same session. Atrioventricular block persisted in all 10 patients successfully treated with radiofrequency ablation during a mean follow-up of 4.2 months. Compared with a group of historic control subjects treated with direct-current shock ablation, the 10 patients successfully treated with radiofrequency current had significantly less creatine kinase-MB isoenzyme release (5.7 +/- 5.1 vs. 22 +/- 13 IU, p = 0.006). A junctional escape rhythm was present in all patients after radiofrequency-induced atrioventricular block. In contrast, three of 10 control patients had an idioventricular escape after direct current shock ablation, and four patients had no escape rhythm at all.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598420 TI - Electrophysiologic effects of dipyridamole on atrioventricular nodal conduction and supraventricular tachycardia. Role of endogenous adenosine. AB - Exogenous adenosine has been shown to have potent electrophysiologic effects and antiarrhythmic properties within the atrioventricular (AV) node. Endogenous adenosine, a nucleoside with an increased release signaled by ischemia and hypoxia, is not believed to exert significant effects during homeostatic conditions. Recent experimental evidence suggests, however, that under normoxic conditions, the amount of adenosine released may be sufficient to mediate some of its physiologic effects. This study was designed to test the hypothesis that in humans the electrophysiologic effects of endogenously released adenosine on AV nodal conduction can be demonstrated under normoxic conditions by inhibiting uptake and degradation of the nucleoside. In the first protocol, the effects of intravenous dipyridamole (0.56 mg/kg bolus i.v., 5 micrograms/kg/minute infusion), a nucleoside-transport blocker that elevates endogenous plasma levels of adenosine, on AV nodal conduction were evaluated in seven patients. At a constant atrial paced cycle length, dipyridamole increased the AH interval from 110 +/- 19 to 164 +/- 26 msec, p = 0.002 (+/- SEM). Aminophylline (5.6 mg/kg i.v.), a competitive antagonist of adenosine, completely reversed the effects of dipyridamole on AV nodal conduction. Similarly, dipyridamole increased the cycle length at which pacing-induced AV nodal Wenckebach occurred, from 348 +/- 31 (control) to 388 +/- 33 msec (dipyridamole) (p = 0.002). In a second protocol, the effects of intravenous dipyridamole were evaluated in another group of six patients who had supraventricular tachycardia (SVT) in which the AV node was part of the reentrant circuit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598421 TI - Recurrent ischemia more than 1 year after successful percutaneous transluminal coronary angioplasty. An analysis of the extent and anatomic pattern of coronary disease. AB - Of 1,181 consecutive patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) as an initial revascularization procedure and who had at least 1 year of asymptomatic follow-up, 66 (6%) underwent repeat angiography because of recurrent symptoms or evidence of exercise-induced ischemia. Patients who had revascularization procedures within 1 year of PTCA were not included in the analysis. Mean time to recurrent ischemia was 30.8 +/- 17.4 months (range 12 89 months). At follow-up, 47 patients had angina, 13 had atypical chest pain, two had acute myocardial infarction, and four had positive exercise tests without symptoms. No patient showed spontaneous regression in the extent of coronary artery disease (CAD). As compared with the extent of CAD immediately after PTCA, the extent of CAD at follow-up did not change in 26 patients (39%); it increased by one vessel in 30 (45%), by two vessels in seven (11%), and by three vessels in three (5%). The pattern of CAD seen at follow-up compared with that seen after PTCA was as follows: 18 patients (27%), no change; seven (11%), restenosis only; 30 (45%), progression of CAD at other sites only; and 11 (17%), a combination of restenosis and progression of CAD at other sites. The time to recurrence of ischemia was significantly different between those with restenosis only versus those with progression only (20.1 +/- 9.2 vs. 38.3 +/- 18.5 months) (p less than 0.009). Progression of CAD was equally distributed between dilated and nondilated vessels; however, when progression occurred in the PTCA vessel, it was significantly more likely to be distal to the PTCA site (p less than 0.008). PMID- 2598422 TI - Exercise treadmill testing is a poor predictor of anatomic restenosis after angioplasty for acute myocardial infarction. AB - This study evaluated whether an exercise treadmill test could predict restenosis in 289 patients 6 months after a successful emergency angioplasty of the infarct related artery for acute myocardial infarction. After excluding those with interim interventions (64), medical events (36), or medical contraindications to follow-up testing (25), both a treadmill test and a cardiac catheterization were completed in 144 patients, 88% of those eligible for this assessment. Four patients with left bundle branch block or pacemaker rhythm at the time of treadmill testing were also excluded from analysis. Of six follow-up clinical and treadmill variables examined by multivariable logistic regression analysis, only exercise ST deviation was independently correlated with restenosis at follow-up (chi 2 = 5, p = 0.02). The clinical diagnosis of angina at follow-up, although marginally related to restenosis when considered by itself (p = 0.04), did not add significant information once ST deviation was known. The sensitivity of ST deviation of 0.10 mV or greater for detecting restenosis was only 24% (13 of 55 patients), and the specificity was 88% (75 of 85 patients). The sensitivity of exercise-induced ST deviation for detection of restenosis was not affected by extent or severity of wall motion abnormalities at follow-up, by the timing of thrombolytic therapy or of angioplasty, or by the presence of collateral blood flow at the time of acute angiography. A second multivariable analysis evaluating the association of the same variables with number of vessels with significant coronary disease at the 6-month catheterization found an association with both exercise ST deviation (p = 0.003) and exercise duration (p = 0.04). Angina symptoms and exercise treadmill test results in this population had limited value for predicting anatomic restenosis 6 months after emergency angioplasty for acute myocardial infarction. PMID- 2598423 TI - Noninvasive determination of coronary artery bypass graft patency by cine magnetic resonance imaging. AB - Cine magnetic resonance imaging (MRI) is a gradient-recalled, retrospectively gated, fast-scan technique that depicts laminar flowing blood as bright signal and has been proposed as a useful method for determination of coronary artery bypass graft (CABG) patency. Therefore, we performed a blinded prospective study to assess the value of cine MRI determination of CABG patency in 20 patients with 45 CABG proximal anastomoses who were undergoing repeat angiography. Ten normal subjects served as controls to define normal intrathoracic vascular patterns. There were 21 left anterior descending (LAD) grafts, of which four were left internal mammary (LIMA), 12 left circumflex (Cx), and 12 right coronary (RCA) grafts. After localizing spin-echo coronal images were obtained, multiple axial multislice interleaved cine MRI acquisitions, each consisting of two to four 5-10 mm-thick slices at eight to 24 frames per cardiac cycle, were obtained from the superior main pulmonary artery to the inferior left ventricle. Each acquisition took 5-8 minutes with a subsequent 5-10 minutes of computer image reconstruction. Total study time per patient was 50-75 minutes. Known to cine MRI interpreters were the original surgical CABG insertions but not the angiographic findings. A graft was called patent if a bright graft flow signal, not corresponding to a normal vessel, was identified on multiple frames at multiple levels abutting the great vessels or epicardial surface of the heart. Angiographically, there were 33 patent grafts, of which 29 were identified as patent by cine MRI (sensitivity, 88%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598424 TI - Impact of compensatory enlargement of atherosclerotic coronary arteries on angiographic assessment of coronary artery disease. AB - To determine whether compensatory enlargement of atherosclerotic coronary arteries occurs and to what degree it affects the angiographic assessment of coronary artery disease, we performed postmortem coronary angiography of 30 human hearts with suspected coronary artery disease and studied 70 histologic cross sections of the proximal left anterior descending artery and proximal right coronary artery. Angiographic and morphometric analyses of 50 stenoses in proximal and middle sections of the left anterior descending artery, right coronary artery, and left circumflex artery were performed. The control group of 10 human hearts without suspected coronary artery disease was evaluated in the same way. For this purpose, coronary arteries were filled with a methylmethacrylic radiopaque resin at a pressure of 100 mm Hg and closely embedded in a methylmethacrylic resin by use of which shrinkage and mechanical artifacts could be avoided. The area circumscribed by the internal elastic lamina was taken as a measure of the area of the arterial lumen if no plaque had been present. The angiographic and corresponding morphometric degree of stenosis was assessed. A significant correlation (r = 0.85, p less than or equal to 0.0001) was found between the internal elastic lamina area and the area of the plaque (lesion area), suggesting that coronary arteries may enlarge as lesion area increases. With the morphometric degree of stenosis, the expected anatomic diminution of the coronary artery was abolished (r = 0.79, p less than or equal to 0.0001), indicating compensatory enlargement in atherosclerotic segments. Accordingly, the degree of stenosis assessed from in vitro angiograms was underestimated. Compensatory coronary enlargement of the stenotic segment was the main reason for angiographic underestimation. The underestimation factor of up to 3.50 for very mild stenoses decreased to 1.37 at an angiographic degree of 50% area stenosis and 30% diameter stenosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598425 TI - Four-year follow-up study in patients with angina pectoris and normal coronary arteriograms ("syndrome X") AB - In patients with typical stress-induced anginal pain, normal coronary arteries, and unimpaired left ventricular performance at rest ("syndrome X"), a reduced coronary dilatory capacity, abnormal lactate metabolism during stress, and reduction of left ventricular functional reserve have been described. A group of 40 patients with syndrome X was followed for several years to determine their long-term prognosis. In 27 patients pulmonary artery pressure and in 19 patients left ventricular ejection fraction were reassessed during rest and exercise approximately 4 years after the initial examination. In patients with stress induced ST-segment depression, these variables did not change during the observation period. In patients with constant or rate-dependent left bundle branch block, however, there was significant deterioration of left ventricular performance during rest (pulmonary artery mean pressure, 16 +/- 3 vs. 17 +/- 4 mm Hg, p = NS; left ventricular ejection fraction, 62 +/- 5% vs. 55 +/- 5%, p less than 0.05) and exercise (pulmonary artery, 30 +/- 6 vs. 39 +/- 10 mm Hg, p less than 0.005; left ventricular ejection fraction, 59 +/- 6% vs. 49 +/- 5%, p less than 0.01). These findings suggest that in syndrome X two subgroups with distinctly different prognoses may be defined: In patients with stress-induced ST segment depression during exercise, left ventricular performance remains well preserved; however, in patients with either constant or rate-dependent left bundle branch block, there is significant deterioration of left ventricular function within several years. PMID- 2598426 TI - Prognosis in patients with low left ventricular ejection fraction after myocardial infarction. Importance of exercise capacity. AB - The measurement of left ventricular ejection fraction (LVEF) plays a key role in many strategies for managing patients after acute myocardial infarction. We tested the hypothesis that exercise capacity 1 month after myocardial infarction provides additional information in patients with a low LVEF and therefore assists in risk stratification. One hundred fifteen patients, with documented myocardial infarction and LVEF less than 35% by gated radionuclide scan 1 month after acute myocardial infarction, were followed up for 2 months to 7 years. Exercise capacity was estimated from a treadmill test 1 month after infarction. Using the Cox proportional hazards model, exercise capacity was a significant predictor of death or reinfarction. The relative risk of death, based on a comparison between the lowermost quintile (less than 4 METS) and uppermost quintile (greater than 7 METS), was 3.5 (95% confidence interval, 1.1-9.7); the relative risk in the fourth, third, and second quintile was 2.7, 2.1, and 1.6, respectively. In a multivariate analysis, the observed effect of a good exercise capacity was independent of LVEF. These data indicate that in patients with a low LVEF after myocardial infarction, useful prognostic information can be obtained from exercise testing. PMID- 2598427 TI - Selective enhancement of the cardiac sympathetic response to exercise by anginal chest pain in humans. AB - Cardiac and whole body [3H]norepinephrine kinetics were used to evaluate the response of overall and cardiac sympathetic activity to supine bicycle exercise in 31 patients with coronary artery disease (CAD) and in nine normal control subjects (group 1). Of the 31 patients with CAD, 20 developed evidence of myocardial ischemia during exercise (group 2), typical angina occurring in 20 of 20 and ischemic ST segment changes in 13 of 20, whereas 11 patients developed no evidence of ischemia (no chest pain or electrocardiographic changes) (group 3). Exercise resulted in increased total and cardiac NE spillover in all groups of patients. Basal cardiac NE spillover was similar in the three groups (group 1, 5 +/- 1 ng/min; group 2, 8 +/- 1 ng/min; group 3, 7 +/- 2 ng/min; p = NS), but during exercise, cardiac NE spillover was greater in patients who developed angina (group 2, 30 +/- 5 ng/min) than in those who did not (group 1, 17 +/- 2 ng/min; group 3, 17 +/- 2 ng/min; p less than 0.05). The increases in total NE spillover were similar in the three groups. Supine bicycle exercise increases cardiac and overall sympathetic tone in normal control subjects and in patients with CAD. The occurrence of angina selectively enhances the cardiac sympathetic response to exercise. In the absence of angina, patients with CAD and control subjects without CAD have similar sympathetic responses to exercise. PMID- 2598428 TI - Noninvasive determination of age-related changes in the human arterial pulse. AB - Arterial pressure waves were recorded noninvasively from the carotid, radial, femoral, or all three of these arteries of 1,005 normal subjects, aged 2-91 years, using a new transcutaneous tonometer containing a high fidelity Millar micromanometer. Waves were ensemble-averaged into age-decade groups. Characteristic changes were noted with increasing age. In all sites, pulse amplitude increased with advancing age (carotid, 91.3%; radial 67.5%; femoral, 50.1% from first to eighth decade), diastolic decay steepened, and diastolic waves became less prominent. In the carotid pulse, there was, in youth, a second peak on the downstroke of the waves in late systole. After the third decade, this second peak rose with age to merge with and dominate the initial rise. In the radial pulse, a late systolic wave was also apparent, but this occurred later; with age, this second peak rose but not above the initial rise in early systole, even at the eighth decade. In the femoral artery, there was a single systolic wave at all ages. Aging changes in the arterial pulse are explicable on the basis of both an increase in arterial stiffness with increased pulse-wave velocity and progressively earlier wave reflection. These two factors may be separated and effects of the latter measured from pressure wave-contour analysis using an "augmentation index," determined by a computer algorithm developed from invasive pressure and flow data. Changes in peak pressure in the central (carotid) artery show increasing cardiac afterload with increasing age in a normal population; this can account for the cardiac hypertrophy that occurs with advancing age (even as other organs atrophy) and the predisposition to cardiac failure in the elderly. Identification of mechanisms responsible offers a new approach to reduction of left ventricular afterload. PMID- 2598429 TI - Noninvasive detection of skeletal muscle underperfusion with near-infrared spectroscopy in patients with heart failure. AB - The present study was undertaken to determine whether near-infrared spectroscopy can be used to noninvasively assess skeletal muscle oxygenation in patients with heart failure. The difference between light absorption at 760 and 800 nm was used to assess hemoglobin-myoglobin oxygenation. Initial studies conducted in isolated canine gracilis muscle demonstrated that 760-800-nm absorption correlated closely (r = -0.97 +/- 0.01) with venous hemoglobin O2 saturation when the muscle was stimulated to contract at 0.25-5.0 Hz. In normal subjects (n = 6) and patients with heart failure (n = 8), 760-800-nm absorption changes from the vastus lateralis muscle were monitored at rest, during progressive maximal bicycle exercise, and during thigh cuff inflation to suprasystolic pressure, an intervention designed to assess minimal hemoglobin-myoglobin oxygenation. Absorption changes were expressed relative to the full physiologic range noted from rest to thigh cuff inflation. During exercise, normal subjects exhibited an initial increase in hemoglobin-myoglobin oxygenation followed by a progressive decrease in oxygenation to 27 +/- 13% of the physiologic range at the peak exercise workload of 140 +/- 9 W. In contrast, patients exhibited an initial decrease in hemoglobin-myoglobin oxygenation with the first workload, followed by a progressive further decrease to 26 +/- 13% of the physiologic range at a peak exercise workload of 60 +/- 8 W, less than half the peak workload noted in the normal subjects. At all exercise loads, hemoglobin-myoglobin oxygenation was significantly less in the patients than in the normal subjects. These data suggest that near-infrared spectroscopy can detect impaired skeletal muscle O2 delivery in patients with heart failure. This technique could provide a valuable method of assessing muscle O2 delivery in patients, particularly before and after therapeutic interventions. PMID- 2598430 TI - Diverse mechanisms of unexpected cardiac arrest in advanced heart failure. AB - To define the mechanisms of unexpected cardiac arrest in advanced heart failure, we reviewed the causes of cardiac arrest as established from electrocardiographic monitoring and from clinical and autopsy data in patients hospitalized for cardiac transplantation evaluation and management of advanced heart failure (mean left ventricular ejection fraction, 0.18 +/- 0.08) who were stable while on vasodilator and diuretic therapy such that hospital discharge to home was anticipated. Twenty-one cardiac arrests occurred in 20 of 216 (9%) such patients during a 4-year period. Heart failure was due to coronary artery disease with prior myocardial infarction in 13 patients and nonischemic cardiomyopathy in seven patients. The rhythm at the time of arrest was severe bradycardia or electromechanical dissociation (BA/EMD) in 13 (62%) patients. The precipitating cause of the BA/EMD arrest was coronary artery thrombosis or embolism in two patients, pulmonary embolism in one patient, hyperkalemia in two patients, and unexplained hypoglycemia in one patient. In seven of 13 (54%) patients, a precipitating cause of the bradycardia arrest could not be established. Only eight of 21 (38%) arrests were due to ventricular tachycardia or fibrillation (VT/VF), and all occurred in patients with prior myocardial infarction (p = 0.02 vs. BA/EMD arrests). Two VT/VF arrests were due to acute or recent infarction, and one patient had hyperkalemia. The patients who suffered a BA/EMD arrest were similar to those who had a VT/VF arrest in age, ventricular arrhythmia history, ventricular function, and serum potassium levels. Serum sodium levels were lower in patients with BA/EMD arrests (129 +/- 3 vs. 133 +/- 4 meq/l, p = 0.025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598432 TI - Two-dimensional echocardiographic and color flow Doppler evaluation of ductal occlusion with the Rashkind prosthesis. AB - To evaluate the results of ductal occlusion with the Rashkind prosthesis, 78 children (group 1, 19 boys and 59 girls; mean age at occlusion, 4.5 +/- 4.0 years) with isolated patent ductus arteriosus (n = 73) or in association with other lesions (n = 5) were evaluated by pulsed and color flow Doppler 9 +/- 7 months (range, 2-26 months) after occlusion. Thirty children who had undergone patent ductus arteriosus ligation (group 2, 9 boys and 21 girls; mean age at study, 5.7 +/- 4.9 years; mean follow-up after ligation, 44 +/- 58 months) were evaluated in the same way. The prevalence of residual ductal shunting and the main pulmonary arterial flow patterns were recorded. Residual ductal shunting in group 1 was 38% on day 1, decreasing slowly to 31% at 3 months, 27% at 6 months, and 19.7% at 1 year or more due to further spontaneous shunt resolution. The residual shunting rate in group 2 (6%) was significantly lower than that at 1 year or more in group 1 (p less than 0.001). Successful reocclusion in 5 of 6 in a subset of patients in group 1 followed for 1 year or less reduced further the prevalence of residual shunting. Residual shunting after patent ductus arteriosus occlusion is more common than after ligation, but continues to decrease during follow-up. PMID- 2598431 TI - Results of the arterial switch operation for transposition of the great arteries with ventricular septal defect. Surgical considerations and midterm follow-up data. AB - Between January 1983 and December 1987, 62 patients underwent an arterial switch operation for transposition of the great arteries with ventricular septal defect or double outlet right or left ventricle. There were three hospital deaths (4.8%), and no deaths occurred in neonates (less than 1 month of age, n = 18). There were three late deaths, one due to coronary obstruction and two due to pulmonary vascular obstructive disease. One child has been lost to follow-up. We have prospectively evaluated the remaining 55 survivors by clinical evaluation, echocardiography, cardiac catheterization, ambulatory electrocardiographic monitoring, and limited electrophysiologic studies. The mean length of follow-up has been 27 +/- 16 months since surgery. One child has required reoperation for a residual ventricular septal defect; no child has undergone reoperation for supravalvar pulmonary or aortic stenosis. Aortic regurgitation was identified in 12 children (22%), which was mild in 11 and moderate in one. One child has asymptomatic occlusion of the left main coronary artery, one child has a tiny right coronary artery-to-pulmonary artery fistula, and one child has abnormal left ventricular wall motion according to follow-up angiography. No other abnormalities of systemic (left) ventricular function have been identified at late follow-up. In addition to the two late deaths due to pulmonary vascular obstructive disease, three children, all of whom were repaired at more than 6 months of age, have elevated pulmonary vascular resistance. Notable postoperative arrhythmias include complete heart block in four patients and nonsustained supraventricular or ventricular tachycardia early after surgery in eight patients (all resolved without medication at later follow-up). Only two patients have evidence of sinus node dysfunction and have not required treatment. The low hospital mortality and encouraging early follow-up data represent a significant improvement over atrial level repairs, supporting the arterial switch operation as the procedure of choice for children who have transposition of the great arteries with ventricular septal defect or double outlet ventricle. Because of the potential for the development of early pulmonary vascular obstructive disease in these patients, repair is recommended within the first 2 months of life. PMID- 2598434 TI - Morphometric analysis of the composition of atherosclerotic plaques in the four major epicardial coronary arteries in acute myocardial infarction and in sudden coronary death. AB - We studied at necropsy atherosclerotic plaque composition in the four major (right, left main, left anterior descending, and left circumflex) epicardial coronary arteries in 15 patients who died of consequences of an acute myocardial infarction (AMI) and in 12 patients with sudden coronary death (SCD) without AMI. The coronary epicardial arteries were sectioned at 5-mm intervals, and a Movat stained section of each segment of artery was prepared and analyzed using a computerized morphometry system. Within the AMI group and within the SCD group, there were no differences in plaque composition among any of the four major epicardial coronary arteries. Within both groups, plaque morphology varied as a function of cross-sectional-area narrowing of the segments. In both groups, the amount of dense relatively acellular fibrous tissue, calcified tissue, and pultaceous debris (amorphous debris containing cholesterol clefts, presumably rich in extracellular lipid) increased in a linear fashion with increasing degrees of cross-sectional-area narrowing of the segments, and the amount of cellular fibrous tissue decreased linearly. In the AMI group, the percentage of plaque consisting of pultaceous debris and of cellular fibrous tissue separated significantly narrowed (greater than 75% cross-sectional area) segments from less narrowed (less than 75%) segments. A comparison of the AMI group to the SCD group showed significant differences. The percentage of plaque consisting of pultaceous debris (16% in the AMI group and 7% in the SCD group), of cellular fibrous tissue (11% vs. 18%), and of heavily calcified tissue (8% vs. 16%) were significantly different in the severely narrowed segments in the AMI and SCD groups. When all arteries containing thrombi were deleted from the analysis, there were no significant changes in the results. Occlusive coronary thrombi were present in 13 of the 15 AMI patients and in one of the 12 SCD patients. Thus, the frequency of coronary thrombi and plaque composition differ in patients with AMI and in those with SCD without AMI. PMID- 2598433 TI - Fetal cardiac and peripheral arterial flow velocity waveforms in intrauterine growth retardation. AB - Maximum flow velocity waveforms were studied at the cardiac level (ascending aorta, pulmonary artery, and ductus arteriosus) and at the peripheral level (fetal internal carotid artery, descending aorta, umbilical artery, and maternal uteroplacental artery) in 25 patients with intrauterine growth retardation and 25 normal control subjects matched for gestational age and maternal parity. Gestational age ranged from 27 to 35 weeks (median, 30 weeks). All flow velocity waveforms were obtained with a mechanical sector scanner combined with a pulsed and continuous Doppler system with a carrier frequency of 3.5 and 3.0 MHz. Normal pregnancy was characterized by low fetal and placental vascular resistances. The peak systolic velocity in the ascending aorta was significantly higher compared with the pulmonary artery. In patients with intrauterine growth retardation, reduced end-diastolic flow velocities were documented in fetal descending aorta, umbilical artery, and maternal uteroplacental artery, reflecting raised umbilical placental and uteroplacental vascular resistances. Raised end-diastolic flow velocities were observed at the cerebral level, reflecting reduced cerebral vascular resistance ("brain sparing" effect). Reduced peak systolic flow velocities documented at the cardiac level may be secondary to reduced volume flow, increased valve or vessel size, or raised afterload. The noninvasive nature of this study did not allow differentiation between these variables. PMID- 2598435 TI - Is tau a preload-independent measure of isovolumetric relaxation? AB - Several studies have been performed in patients with a variety of myocardial diseases that have identified a prolongation of tau. However, it is not clear whether prolongation of tau represents abnormal myocardial physiology or the effect of excessive load associated with a particular disease process. Accordingly, we evaluate the effect on tau of an isolated decrease in preload induced by inferior vena cava occlusion before the appearance of reflex changes in six patients designated as normal by catheterization criteria. A computer based digitization routine identified cardiac contractions in all patients early after inferior vena cava occlusion where left ventricular end-diastolic pressure decreased (18.3 +/- 6.3 to 9.3 +/- 5.8, p less than 0.05) while left ventricular systolic pressure (113.3 +/- 13.8 to 111.8 +/- 14.0, p = NS) and heart rate (66.0 +/- 10.0 to 65.9 +/- 10.3, p = NS) did not change. After this alteration in preload, no change in tau from baseline, as calculated by the logarithmic (TL), derivative (TD), or method of Mirsky (T1/2), was noted: TL, 47.4 +/- 6.5 to 44.6 +/- 7.6; TD, 39.3 +/- 8.1 to 39.8 +/- 8.4; T1/2, 33.0 +/- 4.0 to 31.8 +/- 4.6; all p = NS. The baseline pressure extrapolated from isovolumetric relaxation did not change in these preload beats compared with baseline (+4.26 +/- 6.20 to -0.80 +/- 4.87, p = NS). Subsequent beats were identified where left ventricular systolic pressure showed a numeric decrease compared with baseline (113.3 +/- 13.8 to 100.8 +/- 14.3, p = NS) despite no change in heart rate (66.0 +/- 10.0 to 66.8 +/- 10.5, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598436 TI - Abolition of in vivo platelet thrombus formation in primates with monoclonal antibodies to the platelet GPIIb/IIIa receptor. Correlation with bleeding time, platelet aggregation, and blockade of GPIIb/IIIa receptors. AB - We studied the dose-response effects of the F(ab')2 fragments of murine monoclonal antibodies to the platelet GPIIb/IIIa receptor (7E3 and 10E5) on in vivo platelet thrombus formation in a well-characterized monkey model in which the carotid artery is stenosed and thrombus formation is provoked and augmented by intimal damage and the infusion of subaggregating doses of epinephrine. Both antibodies abolished thrombus formation with a mean dose of -0.2 mg/kg. Ex vivo platelet aggregation was not always abolished at doses that abolished thrombus formation; similarly, bleeding times were only moderately prolonged (9.1 +/- 1.4 minutes) at these doses. Increasing the dose above that required to abolish thrombus formation consistently produced abolition of ex vivo platelet aggregation, marked prolongation of the bleeding time (14.2 +/- 1.5 minutes), and nearly quantitative blockade of GPIIb/IIIa receptors. We conclude that in a significant percentage of animals, the extent of GPIIb/IIIa blockade required to prevent vasoocclusive thrombus formation in this model is less than that required for abolition of platelet aggregation, and that the preservation of only a minority of functional GPIIb/IIIa receptors might be adequate to maintain a nearly normal bleeding time. PMID- 2598437 TI - Determinants of end-systolic pressure-volume relations during acute regional ischemia in situ. AB - The influence of extent and location of regional ischemia, baseline left ventricular systolic function, and autonomic reflexes on in situ left ventricular end-systolic pressure-volume relations (ESPVRs) during coronary occlusion were studied in 13 open-chest dogs. Circumflex or left anterior descending arteries were randomly occluded (at proximal or distal sites) for 3 minutes in reflex blocked (n = 6, hexamethonium/vagotomy) and unblocked (n = 7) animals. Pressure volume data were obtained by the conductance-catheter technique, with ESPVRs determined by transient inferior vena caval occlusion. Ischemic zone size was estimated for each occlusion by radiolabeled microspheres. The relative influence of each variable on ESPVR change with ischemia was determined by multiple regression analysis. As in previous studies, regional ischemia displaced ESPVRs to the right by an amount that varied directly with ischemic bed size (y = +0.48x, r = 0.76, p less than 0.001). However, in contrast to previous data, coronary occlusion also reduced the ESPVR slope (end-systolic elastance, Ees) in the majority of cases. The extent of slope change was primarily dependent on the baseline elastance (Eesbase), such that the higher the initial elastance, the larger its subsequent reduction for any amount of ischemia (delta Ees = 0.78Eesbase, r = 0.94, p less than 0.001). Active reflexes added an offset constant to this relation (+3.15 mm Hg/ml, p less than 0.001). In addition, Ees fell slightly more with larger ischemic regions. Thus, although previous studies have reported primarily rightward parallel shifts in ESPVR with regional ischemia, the present data also demonstrate that the slope of the relation is often reduced. Greater baseline elastances typical of in situ, as opposed to isolated, ventricles probably explain the differences in apparent responses. PMID- 2598438 TI - Relation between myocardial glutathione content and extent of ischemia reperfusion injury. AB - The relation between the extent of myocardial injury sustained during reperfusion and total glutathione (GSH) content in the ischemic myocardium was examined in anesthetized open-chest pigs subjected to coronary occlusion for 45 minutes and reperfusion for 2 hours. In pigs infused with saline during reperfusion (n = 6) there was a decrease in myocardial GSH content from 380 +/- 48 micrograms/g in normally perfused myocardium to 182 +/- 36 micrograms/g in the ischemic reperfused myocardium (p less than 0.02). Myocardial infarct size (expressed as a percentage of the ischemic area) was 12.5 +/- 0.8%. There was a delay of recovery of contractile function before returning to 60% of preocclusion value. In pigs pretreated with buthionine sulfoximine (BSO) (n = 5), an inhibitor of cellular GSH synthesis, there was reduction in GSH content to 215 +/- 25 micrograms/gm in normally perfused myocardium and to 77 +/- 8 micrograms/gm in the ischemic reperfused myocardium. The extent of injury was greater as evidenced by an increase in infarct size to 30.4 +/- 4.0% (p less than 0.001), severe destructive changes in subepicardial ultrastructure, which were absent in saline-infused pigs, and persistence of dyskinesia throughout reperfusion. In pigs infused with glutathione intravenously (0.8 gm/kg) at a rate of 6.5 mg/kg/min (n = 6), 5 minutes before and continuously during reperfusion, there was an increase in GSH content to 582 +/- 67 micrograms/g in normally perfused myocardium and to 312 +/- 80 micrograms/g in ischemic reperfused myocardium. The increase in myocardial GSH was associated with a reduction in infarct size to 7.5 +/- 1.3% (p less than 0.05, compared with saline-infused pigs) and an early recovery of contractile function of the ischemic myocardium. GSH infusion into pigs pretreated with BSO (n = 4) failed to increase myocardial GSH content and failed to reduce the extent of myocardial injury. Thus, the extent of myocardial injury sustained during reperfusion is very dependent on the effectiveness of its antioxidant defenses. Markedly increased susceptibility to injury occurs when the GSH content in the ischemic myocardium becomes depleted. PMID- 2598439 TI - Effect of a critical coronary stenosis on myocardial neutrophil accumulation during ischemia and early reperfusion in dogs. AB - In many experimental models of ischemia and reperfusion, reperfusion is performed abruptly, allowing full reactive hyperemia to occur. In the clinical setting, however, reperfusion after thrombolysis is often limited by residual stenosis. Some experimental models attempt to mimic this situation with a "critical stenosis" (defined as a coronary constriction sufficient to abolish reactive hyperemia without altering baseline flow). The purpose of this study was to determine whether preventing reactive hyperemia during the initial phase of reperfusion would modify the transmural distribution of myocardial blood flow or the myocardial accumulation of polymorphonuclear leukocytes (PMNs). The left circumflex artery was occluded for 90 minutes and then reperfused for 60 minutes in anesthetized, open-chest dogs. Autologous PMNs were isolated, labeled with 111In, and reinjected 1 hour before coronary occlusion. 125I-labeled albumin was injected simultaneously to correct for 111In associated with plasma proteins and to permit calculation of the number of PMNs in the inner, middle, and outer thirds of nonischemic and ischemic-reperfused tissue. The presence of a critical stenosis abolished reactive hyperemia during the first 5 minutes of reperfusion, but did not substantially affect blood flow measured after 55 minutes of reperfusion. In both groups, there was a significant accumulation of PMNs in all layers of the ischemic-reperfused bed compared with the nonischemic bed, and the magnitude of this PMN accumulation was not altered by the presence of a critical stenosis. Moreover, infarct size, estimated by triphenyl tetrazolium chloride (TTC) loss after 60 minutes of reperfusion, was not affected by the presence of a critical stenosis. Thus, the presence of a critical stenosis abolished the hyperemic blood flow after reperfusion but did not influence the early PMN response to ischemia and reperfusion or the early loss of TTC staining. PMID- 2598440 TI - Neutrophil depletion limited to reperfusion reduces myocardial infarct size after 90 minutes of ischemia. Evidence for neutrophil-mediated reperfusion injury. AB - Reperfusion of ischemic myocardium may accelerate necrosis of injured myocytes. To determine the role of neutrophil leukocytes in this process, we examined whether neutrophil depletion during reperfusion could modify infarct size in anesthetized dogs. The proximal circumflex coronary artery was occluded for 90 minutes and then reperfused for 2 hours via an extracorporeal circuit with either whole blood (n = 11) or with blood depleted of neutrophils by leukocyte filters (n = 11). The leukocyte filters caused near-total neutropenia in blood reperfusing the ischemic myocardium (7 +/- 7 neutrophils/microliters compared with 2,551 +/- 317/microliters in controls, mean +/- SEM; p less than 0.001. Infarct size was measured by planimetry of myocardial slices stained with triphenyltetrazolium chloride (TTC), and the accuracy of TTC for identifying necrotic myocardium was verified by electron microscopy. The size of the ischemic risk region was the same in the control (41.6 +/- 1.0%) and neutropenic (41.8 +/- 2.1%) groups. Collateral blood flow to the risk region was the same in control (0.15 +/- 0.03 ml/min/g) and neutropenic (0.13 +/- 0.03 ml/min/g) groups. Among dogs with collateral flow less than 0.2 ml/min/g, infarct size was reduced in the neutropenic group (27.7 +/- 6.7% of risk region, n = 8), compared with control dogs (52.5 +/- 5.7%; n = 7; p = 0.02). Multiple linear regression described the relation between infarct size, risk region size, and collateral flow in the control group, and the same regression relation was used to predict infarct size for the neutropenic group. Mean predicted infarct size in the neutropenic group (n = 11) was 16.8 +/- 3.4% of left ventricle, whereas mean observed infarct size was 9.6 +/- 3.1% (p less than 0.01). The extent of the no-reflow zone (absence of thioflavin-S-fluorescence) was also less in the neutropenic than the control group (2.2 +/- 0.8% vs. 8.1 +/- 2.7% of the risk region, p less than 0.05). Neutropenia limited to the reperfusion period is associated with significant reductions in the extent of the infarct and no-reflow zones after 90 minutes of ischemia. These findings support the hypothesis that reperfusion necrosis occurs after prolonged myocardial ischemia and indicate that neutrophil leukocytes are important mediators of such reperfusion injury. PMID- 2598441 TI - Alleviation of myocardial stunning by leukocyte and platelet depletion. AB - Neutrophils accumulate in myocardium rendered ischemic and reperfused. Activated neutrophils release mediators such as metabolites of oxygen that can compromise myocellular integrity and provoke cardiac dysfunction. Although it is established that leukopenia reduces infarct size, the role of leukocytes and the source of free radicals in postischemic contractile dysfunction is unresolved. A carotid left anterior descending coronary-artery extracorporeal circuit without (n = 8) or with a Leukopak filter (n = 6) to deplete the leukocytes and platelets from blood entering the left anterior descending artery was established in the anesthetized, open-chest dog 30 minutes before ischemia. Subendocardial segmental function was monitored by sonomicrometry, and ischemia was produced by stopping flow for 15 minutes followed by 3 hours of reperfusion. Depleting leukocytes by 90 +/- 3.2% and platelets by 100% improved segmental function (from 30.5 +/- 7% to 74.1 +/- 12.7% for control versus leukocyte-depleted dogs, respectively) at 15 minutes of reperfusion. In the leukopenic group, however, there was a progressive decline in contractility to 32.5 +/- 13.8% by 3 hours of reperfusion that was associated with a return of leukocytes and, to a lesser extent, a return of platelets in the extracorporeal blood to 70.2 +/- 21.9% and 15.5 +/- 4.3% of systemic values, respectively. Removal of leukocytes and platelets from blood perfusing the coronary vascular bed only at reperfusion improved contractile function to 67.7 +/- 6.9% at 15 minutes and 54.7 +/- 12.1% at 3 hours (n = 6). Scanning electron microscopy revealed adherent leukocytes in the epicardial coronary arteries of control animals after 3 hours of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598442 TI - Progressive impairment of regional myocardial perfusion after initial restoration of postischemic blood flow. AB - The "no-reflow" phenomenon, the occurrence of areas with very low flow in hearts reperfused after ischemia, is thought to be largely established at the time of reperfusion as a result of microvascular damage induced by ischemia. In the present study we sought to determine whether additional impairment of tissue perfusion might also occur during the course of reperfusion. Open-chest dogs were subjected to 90 minutes of left circumflex coronary artery occlusion and reperfused for 2 minutes (n = 7) or 3.5 hours (n = 8). Myocardial perfusion was visualized in left ventricular slices following in vivo injection of the fluorescent dye thioflavin-S just before killing. The area of impaired perfusion (absent thioflavin) averaged 9.5 +/- 3.0% of the risk region in dogs reperfused for 2 minutes, whereas it was nearly three times as large in dogs reperfused for 3.5 hours (25.9 +/- 8.2% of the risk region, p less than 0.05). Serial measurements of flow by microspheres during reperfusion demonstrated zones within the postischemic myocardium that were hyperemic 2 minutes after reperfusion, with adequate flow still present at 30 minutes, but with a subsequent marked fall in perfusion. After 3.5 hours these areas showed negligible flow (0.13 +/- 0.3 ml/min/g) and no thioflavin uptake. Tissue samples showing postischemic impairment in perfusion has received virtually no collateral flow during ischemia (less than 0.01 ml/min/g), whereas collateral flow was significantly higher in adjacent thioflavin-positive zones (0.04 +/- 0.01 ml/min/g in endocardial samples and 0.07 +/- 0.02 ml/min/g in samples from the midmyocardium, p less than 0.001 vs. thioflavin-negative areas). Areas that showed late impairment of flow invariably demonstrated contraction band necrosis, which contrasted with the pattern of coagulation necrosis observed in areas of "true" (i.e., immediate) no reflow. Intracapillary erythrocyte stasis and marked intravascular neutrophil accumulation (to levels greater than 20-fold that found after 2 minutes reperfusion) were typically observed in areas of delayed impairment to flow. Obstruction to flow at the capillary level was confirmed in additional dogs in which the heart was injected postmortem with silicone rubber to delineate the microvascular filling pattern. Areas of absent capillary filling were much more extensive after 3.5 hours than after 2 minutes reperfusion. Thus, this study shows that the occurrence of areas of markedly impaired perfusion in postischemic myocardium is related only in part to an inability to reperfuse certain areas on reflow. A more important factor is represented by a delayed, progressive fall in flow to areas that initially received adequate reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2598443 TI - Metabolic protection by verapamil during graded coronary flow reduction independent of effect on baseline systolic function. Separation of mechanical and ionic markers of ischemia. AB - Pretreatment with the calcium channel-blocking agent verapamil lowers the coronary flow associated with the first rise in myocardial extracellular potassium [( K+]e). The mechanisms underlying this effect are unclear. It is not known whether this effect is a manifestation of verapamil-induced reduction in baseline cardiac work before the reduction in coronary flow, is dependent on a selective depression of contractility within the low-flow region, or is independent of an effect on myocardial work. This study was performed to determine the relations between changes in regional contractility and [K+]e before and after verapamil (0.2 mg/kg followed by 6.5 micrograms/kg/min) when left anterior descending (LAD) coronary flow is progressively reduced and when verapamil-induced alterations in baseline myocardial work are prevented by atrial pacing and by dobutamine (4.3 +/- 2.2 micrograms/kg/min) to maintain systemic arterial blood pressure and contractility. Before verapamil-dobutamine, myocardial [K+]e rose and regional contractility fell when LAD coronary flow was reduced to 87.7 +/- 9.6% and 83.4 +/- 7.4%, respectively, of the unrestricted control value (p = NS). After verapamil-dobutamine, the threshold flow for rise in [K+]e decreased to 56.4 +/- 13.5% of the unrestricted control flow (p = 0.003), but the threshold flow for regional contractility fall was unchanged (84.8 +/- 11.3%). Our results indicate that the protective effect of verapamil on preventing ischemia-induced [K+]e release is not dependent on a reduction in baseline myocardial work. In this setting, calcium channel blockade by verapamil results in a dissociation between the ionic and mechanical events that occur when coronary flow is reduced. PMID- 2598444 TI - Reflex responses to myocardial ischemia and reperfusion. Role of prostaglandins. AB - Powerful vasodepressor and cardioinhibitory reflexes are activated in humans during inferior wall myocardial ischemia or infarction and during restoration of flow to the ischemic region. Experiments in dogs have demonstrated that these responses are due to stimulation of afferent vagal fibers that are located mainly in the inferior wall of the heart. Prostaglandins are released during myocardial ischemia and possibly during reperfusion. Prostaglandins stimulate chemosensitive but not mechanosensitive endings in the ventricles. Our studies determined whether blockade of prostaglandin synthesis with indomethacin or sodium meclofenamate decreased the reflex inhibitory responses to coronary occlusion and reperfusion. Experiments were done in alpha-chloralose-anesthetized dogs after sinoaortic baroreceptor denervation. Occlusion of the circumflex coronary artery for 5 minutes resulted in decreases in arterial pressure and in renal sympathetic nerve activity. During the first 5 minutes after release of the occlusion, renal nerve activity remained inhibited. After treatment with indomethacin (n = 6, 5 mg/kg i.v.) or sodium meclofenamate (n = 3, 4 mg/kg i.v.), coronary occlusion resulted in significantly less inhibition of renal nerve activity. Renal nerve activity returned to control during the first minute of reperfusion. In six additional experiments the responses to coronary occlusion and reperfusion were not altered by treatment with vehicle. Our data suggest that prostaglandins serve as the major stimulus to ventricular sensory endings during myocardial ischemia and reperfusion. Our data further suggest that reflex inhibitory responses during ischemia and reperfusion are due mainly to stimulation of chemosensitive endings. PMID- 2598445 TI - Severe aortic stenosis in the sick octogenarian. A clear indicator for balloon valvuloplasty as the initial procedure. PMID- 2598446 TI - Syndrome X. "What's in a name...?". PMID- 2598447 TI - Arterial switch repair for transplantation with ventricular septal defect [corrected]. PMID- 2598448 TI - Platelet inhibition with an antibody to glycoprotein IIb/IIIa. PMID- 2598449 TI - Receptor-specific antiplatelet therapy. PMID- 2598450 TI - VT and sudden death in HCM patients. PMID- 2598451 TI - Digital nerve blockade in Raynaud's disease. PMID- 2598452 TI - Calcium entry blockers: usefulness in ischemia and hypertensive heart disease. September 23 to 28, 1988, Cannes, France. Proceedings. PMID- 2598453 TI - Pharmacology of TA-3090 (8-chloro diltiazem) related to its cerebrovascular protective properties. AB - TA-3090 (8-chloro diltiazem) has been shown in three experimental circumstances to have cerebrovascular protective properties. In vitro investigation of its pharmacology was undertaken to determine the foundation of this effect. Based on contractile responses of rabbit arteries to high potassium and norepinephrine, TA 3090 has some selectivity for cerebral and renal artery potential-sensitive and cerebral receptor-operated calcium-dependent mechanisms. It has no effect on arterial contraction to sympathetic nerve stimulation. It prevents the increase in uptake of 45Ca2+ in response to K+ (80 mM) in rabbit thoracic aorta and antagonizes the contractile effect of the putative cerebrovascular spasmogen alpha-thrombin on the femoral artery. All these effects take place in concentrations below those that significantly depress the action of the rabbit atrium. TA-3090 has little or no effect on other factors known to regulate cerebral blood flow (e.g., stretch-induced contraction and flow-induced contraction and dilation). This spectrum of pharmacologic activity suggests that TA-3090 would selectively block Ca2+ entry into cerebrovascular smooth muscle through potential-sensitive and receptor-operated Ca2+ channels that would be expected to increase in subarachnoid hemorrhage and cerebral ischemia. The action would occur using doses that have little effect on other factors that contribute to the control of cerebral blood flow. PMID- 2598454 TI - Calcium antagonists. Pharmacologic differences and similarities. AB - The available calcium antagonists fall into these broad classes: the dihydropyridines, the benzothiazepines, and the phenylalkylamines. Although they all inhibit calcium entry into cells, the drugs differ in their pharmacodynamic and pharmacokinetic properties. The pharmacodynamic differences arise from the drugs' differing potencies in different tissues and resultant variability in the reflex effects elicited by the drugs' primary effects. PMID- 2598456 TI - Managing sleep disorders in the elderly patient. PMID- 2598455 TI - Exercise-induced allergic syndromes on the increase. PMID- 2598457 TI - Inherited deficiency of alpha 1-antitrypsin and emphysema. Prospects and promise of research. PMID- 2598458 TI - Hospital readmissions: a re-evaluation of criteria. AB - A prospective study surveyed patients discharged from the Cardiology, Cardiovascular Surgery, and Gastroenterology services of the Cleveland Clinic Hospital during April and September 1987. The total number of hospital discharges during the study period was 5,349; the study population discharged during this period included 1,640 patients (30.7% of all hospital discharges). In the study population, 149 patients were readmitted (9.1%). The percentage of readmissions was similar for both months and similar to that reported in the literature. However, when readmissions were categorized into four subsets, significant differences were found. The four categories were: 1) complication of a previous admission (16.8% of readmissions), 2) recurrence of the disease process (11.4% of readmissions), 3) planned treatment (53% of readmissions), and 4) unrelated new diagnosis (16.1% of readmissions). The authors conclude that reviewing readmission rates without using these subdivisions can be misleading, and the results are inappropriate for evaluating the quality of medical care given in an acute care hospital. They recommend that these four subdivisions be included in future studies of readmission rates in acute care hospitals. PMID- 2598459 TI - Biomedical technology, socioeconomics, and biomedical computing: implications for change. AB - Pathology and laboratory medicine have changed rapidly since 1945. Three forces can be recognized as major vectors for change: rapid application of the biotechnology evolving from research in molecular biology, radically changing medical socioeconomics, and the evolving field of medical information science. While these apparently disparate elements affect all of medicine and health care, at the present time they appear to be changing pathology and laboratory medicine to a far greater extent than many other medical specialties. If pathologists fail to make the necessary changes, obsolescence may well overtake the specialty. Planning for the innovative educational and training programs that will be required to meet the future demands of the specialty is essential, not only for those now in practice but for those who will follow us. PMID- 2598460 TI - Immunoglobulin and T-cell receptor gene rearrangement. Implications for the diagnosis of lymphoproliferative disorders. AB - Recent studies have significantly broadened understanding of immunoglobulin production and T-cell receptor formation at the gene level. A limited number of genes can be rearranged during the course of B-cell or T-cell development to yield unique DNA sequences that will code for specific antibodies and T-cell receptor proteins. Southern blot hybridization analysis allows sensitive examination of lymphocyte DNA for the presence or absence of gene rearrangements. General mechanisms that underlie immunoglobulin and T-cell receptor rearrangement are reviewed, along with the diagnostic applications of detection of gene rearrangement by Southern blot hybridization technique. PMID- 2598461 TI - Intra-aortic balloon-pump rupture and entrapment. AB - The authors report a case of intra-aortic balloon rupture and entrapment in a patient with extensive vascular disease. The balloon was subsequently removed percutaneously. A review of the diagnosis and management of this unusual complication is presented. PMID- 2598462 TI - ACHOO syndrome: laboratory findings. AB - The author provides laboratory documentation of the ACHOO syndrome (photic sneeze reflex) and was able to calculate the latency of the reflex. PMID- 2598463 TI - A high performance liquid chromatography method for the analysis of 35S-cystine: application to the diagnosis of cystinosis. AB - An HPLC method for the measurement of radioactively labelled cystine is described. This method has been applied to studies of the uptake and retention of 35S-cystine by cultured cells. Radioactive cystine was measured, as a proportion of the non-protein labelled products in cultured cells incubated with medium containing 35S-cystine. Cells from healthy individuals contained less than 7% cystine whereas cells from cases of cystinosis contained at least 19% cystine. The method has been applied to the prenatal diagnosis of cystinosis. The use of flow radioactivity detection provides the advantages of rapid diagnosis and quantitation of metabolites. PMID- 2598464 TI - Serum lipolytic activity in Reye's syndrome. AB - High levels of the serum free fatty acids (FFA) are found in Reye's syndrome (RS). While this is attributed to enhanced adipose tissue lipolysis, the possibility that intravascular lipolysis could augment this process was investigated by measuring lipase activity in sera from RS and other subjects. Ordinarily, lipolytic activity is not detectable in serum from unheparinized subjects. Significant lipolytic activities ranging from 1-3 mumol/ml serum per hour were detected in sera from 5 of the 7 RS patients studied. Similar activities were also found in sera from two other subjects one of whom was a long term survivor of RS and the other who had recurrent bouts of biliary obstruction and encephalopathy. Lipase activity was negligible in the serum from 2 other RS patients, 4 other long-term survivors of RS, 2 siblings, one RS parent and in 20 disease controls including patients with influenza, diabetic ketoacidosis and cerebral edema, meningitis and febrile infections with diarrhea and vomiting. None of these individuals had received heparin. An inverse relationship was found between LPL and hepatic lipase (HL) activities. Glucose levels tended to correlate directly with LPL and inversely with HL activity. The basis for the presence of LPL activity in RS sera is not known but the presence of serum lipase activity in unheparinized patients supports the notion that the TG in the circulating lipoprotein particles probably also serve as another source of FFA in the sera of RS patients. PMID- 2598465 TI - Serum deoxyribonuclease I determined by a radioimmunoassay and an enzymatic assay in malignant diseases. PMID- 2598466 TI - Immunoreactive anionic and cationic trypsin in human serum. AB - A simple method for the purification of anionic and cationic trypsinogen and trypsin from human pancreatic juice applying affinity chromatography on aprotinin coupled Sepharose is described together with the N-terminal amino acid sequences for both trypsinogens. In addition, enzyme-linked immunoabsorbent assay (ELISA) methods for the determination of anionic and cationic trypsin-like immunoreactivity (irAT and irCT) are described. Normal serum levels are 21.3 +/- 7.4 micrograms/l and 27.8 +/- 9.0 microgram/l for irAT and irCT respectively and the accuracy of these assays is 6-10%. In our population, the normal ratio between irCT and irAT in serum is 1.36 +/- 0.42. In normal serum trypsin-like immunoreactivity consists solely of trypsinogen. In acute pancreatitis there is an increase over normal of both irAT and irCT with a proportionally greater increase in irAT than irCT. Similar changes are also found in uremic patients. PMID- 2598468 TI - Radioimmunoassay of human platelet-derived growth factor using monoclonal antibody toward a synthetic 73-97 fragment of its B-chain. AB - A mouse monoclonal antibody toward a 73-97 fragment of human platelet-derived growth factor (hPDGF) B-chain was used to develop a radioimmunoassay (RIA) for serum hPDGF. By the single step procedure of the double antibody technique, the measurable range was 10-1,000 micrograms/l. The coefficients of variation within and between series were 10.2% and 12.1% respectively, and satisfactory dilution curves were obtained for sera from healthy subjects. The hPDGF levels in all plasma samples from 15 healthy subjects examined were below the detection limit (10 micrograms/l), whereas the mean hPDGF concentration (+/- SD) in serum samples of 60 healthy subjects was 31.9 +/- 20.4 micrograms/l. This value was significantly (p less than 0.01) higher than the mean for 21 patients with idiopathic thrombocytopenic purpura (12.6 +/- 4.5 micrograms/l). There was a significant positive (r = 0.481, p less than 0.01) but not a strong (r2 = 0.23) correlation between the peripheral blood platelet counts and serum hPDGF levels of all subjects. This RIA system should be useful clinically for measurement of serum hPDGF. PMID- 2598467 TI - Analysis of maple syrup urine disease in cell culture: use of substrates. AB - Branched-chain 2-oxo acid dehydrogenase activity in human skin fibroblasts against L-leucine, L-valine, L-isoleucine and derived 2-oxo acids was compared in incubations with 1 mmol/l of 1-14C-labelled substrate. The results suggested that the amino acids are the more suitable substrates for an estimation of decarboxylation activity in intact cells. In control cell lines (n = 12), 14CO2 release from amino acids was highest for valine and least for leucine. In a representative number of fibroblast strains of patients with different forms of MSUD (n = 11; residual decarboxylation activity 2-60% of the controls), 14CO2 release from the different amino acids was reduced to a similar degree. Additional measurement of 2-oxo[1-14C]acid release suggested that substrate supply to the branched-chain 2-oxo acid dehydrogenase complex was not rate limiting in the cell lines under investigation. PMID- 2598469 TI - 3-Methylisoxazol-5-one, an artefact from acetoacetic acid formed during urinary organic acid analysis. AB - During the analysis of urine for organic acids for suspected metabolic disorders by solvent extraction, derivatisation and capillary gas chromatography, unaccountably large lactic acid peaks were observed in some samples containing large amounts of acetoacetic acid. Electron impact mass spectrometry showed that this was due to two unknown compounds coeluting with lactic acid. These were found to be two trimethylsilyl derivatives of 3-methylisoxazol-5-one, produced from acetoacetic acid during oximation with hydroxylamine hydrochloride, by a cyclisation reaction. Awareness of the formation of this previously unreported artefact is important to laboratories employing a similar profiling procedure. PMID- 2598470 TI - The pharmacokinetics, safety and endocrine effects of authentic biosynthetic human growth hormone in normal subjects. AB - The pharmacokinetics, safety and endocrine effects of an authentic human growth hormone (bio-hGH), produced by the expression of genomic hGH in a mammalian cell line, were studied in six healthy young men who were administered 0.2 U/kg/day subcutaneously for five consecutive days. Changes in sodium balance and in thyroid function were studied during the week of bio-hGH administration and safety parameters were monitored over a 3-week period. Growth hormone levels reached a mean (+/- SD) peak of 106 +/- 10 mIU/l at 3.3 +/- 0.5 h following the first dose and resulted in a significant rise of somatomedin C. free fatty acids, fasting blood glucose and insulin concentrations. Bio-hGH administration resulted in a significant increase in body weight (80.0 +/- 4.5 to 81.1 +/- 4.3 kg; P less than 0.01) which was associated with a marked reduction in urinary sodium excretion (196 +/- 38 to 45 +/- 20 mmol/day; P less than 0.025). Serum T3 increased during bio-hGH administration and was associated with reciprocal changes in free thyroxine and TSH concentrations. Cardiac, hepatic, renal, biochemical, haematological, endocrinological and immunological functions remained normal throughout the study. No antibodies to hGH or to host cell protein developed during the study. The results show that bio-hGH is safe in the short term, well tolerated, possesses pharmacokinetic and biological properties similar to pituitary hGH, and has distinct effects on sodium balance and on thyroid function. This study stresses the need to monitor patients for effects on sodium retention, carbohydrate metabolism and thyroid function when using hGH doses of 1.0 U/kg/week (40 U/m2/week) or more in patients with GH responsive short stature. PMID- 2598471 TI - Insulin-like growth factor 1 and bone turnover in glucocorticoid-treated and control subjects. AB - The role of the growth hormone-somatomedin axis in the genesis of steroid osteoporosis has been studied by measuring circulating insulin-like growth factor 1 (IGF-1) levels in asthmatic subjects either receiving or not receiving therapy with oral glucocorticoids. There was no difference in IGF-1 levels between the two groups (60.6 micrograms/l (95% confidence interval 47.3-77.8) in the control subjects vs 69.1 micrograms/l (49.3-96.9) in the steroid-treated group). IGF-1 declined with age in the control subjects but not in those taking steroids. When IGF-1 levels were correlated with biochemical indices of bone turnover, a significant relationship was found with urine hydroxyproline in the control subjects (r = 0.55, P less than 0.02) but not in those taking steroids. It is concluded that glucocorticoid therapy does not alter mean circulating levels of IGF-1 but that the growth hormone-somatomedin axis may influence bone turnover in normal subjects. Interference by glucocorticoids with the normal regulation of IGF-1 and its influence on bone turnover is suggested. PMID- 2598472 TI - The effect of thyroid disease on proinsulin and C-peptide levels. AB - C-peptide and proinsulin levels were studied in hyper and hypothyroidism both pre and post-treatment and in comparison to matched normals. Fasting C-peptide was reduced in untreated hyperthyroidism (0.4 +/- 0.2 (mean +/- SEM) vs 0.7 +/- 0.2 nmol/l, P less than 0.05) but returned to normal levels following treatment. Fasting proinsulin was elevated in untreated hyperthyroidism (3.6 +/- 0.7 vs 2.4 +/- 0.5 pmol/l, P less than 0.05) also returning to normal after treatment. A similar pattern was seen after oral glucose. The increased proinsulin and reduced C-peptide suggest there may be a defect of proinsulin processing in hyperthyroidism. Fasting C-peptide was reduced in untreated hypothyroidism (0.4 +/- 0.1 vs 0.7 +/- 0.1 nmol/l, P less than 0.05) and also returned to normal after treatment. Fasting proinsulin did not differ significantly from controls. However, proinsulin was reduced after oral glucose (4.7 +/- 0.7 vs. 7.9 +/- 2.0 pmol/l, P less than 0.05) as was C-peptide (0.9 +/- 0.2 vs 2.6 +/- 0.3 nmol/l, P less than 0.05). Both returned to normal after treatment. These findings suggest there are abnormalities of proinsulin and C-peptide levels in both hyper and hypothyroidism. PMID- 2598473 TI - Corticotrophin-releasing factor-like immunoreactivity in human 24 h urine. AB - This report is the first demonstration of the presence of corticotrophin releasing factor-like immunoreactive material (CRF-LI) in human urine. Our studies, using immunoaffinity chromatography for extraction, followed by reverse phase high performance liquid chromatography for further purification, and radioimmunoassay for final peptide measurement, suggest that CRF-LI from human urine is similar, if not identical, to human CRF. Urinary CRF-LI excretion in normal subjects was 1.48 +/- 0.69 ng/24 h (mean +/- SD; n = 20) with no significant differences between the sexes. During pregnancy, urinary CRF-LI excretion increased, and a significant correlation between urinary CRF-LI excretion and the gestational age was seen (r = 0.62; P less than 0.0001). We suggest that urinary 24-h CRF-LI excretion may reflect the secretion of CRF into the circulation. Measurements of CRF-LI in the urine may have several advantages over determinations of hormone levels in plasma. PMID- 2598474 TI - Urinary growth hormone during puberty in normal and diabetic children. AB - The measurement of GH in urine may have many clinical applications, particularly in childhood. We have used a highly sensitive direct immunoradiometric assay to examine urinary GH excretion in children during puberty. Fifty-five healthy schoolchildren collected timed overnight urine samples. A further 36 children (15 normal, six of short stature and 15 diabetic) collected urine samples during a total of 50 overnight plasma GH secretory profiles (15-min sampling). Overnight urinary GH excretion increased during puberty, with a peak at breast stage 2 in girls, and genital stage 4 in boys, before declining at stage 5. There was a positive correlation (r = 0.57, p = 0.003) with height velocity in girls, but not in boys. At each puberty stage except 2, the diabetics excreted more urinary GH than the normal children. There was a highly significant correlation (r = 0.79, p less than 0.001) between mean overnight plasma GH concentrations and urinary GH excretion, suggesting that the latter accurately reflects physiological GH secretion. PMID- 2598475 TI - Effect of morphine on cortisol and prolactin secretion in anorexia nervosa and depression. AB - Endogenous opioid peptides are involved in feeding regulation, and alterations in opioidergic regulation have been implicated in the pathophysiology of eating disorders. To investigate further this hypothesis, we conducted a placebo controlled study of the effect of the opiate alkaloid morphine on cortisol and prolactin secretion in six patients with anorexia nervosa and six age-matched healthy volunteers, and compared the results with those obtained in nine depressed patients. Basal cortisol but not basal prolactin levels were elevated in patients with anorexia nervosa and patients with depression. Following the administration of morphine plasma concentrations of cortisol levels declined progressively and at a similar rate in all three groups. The prolactin response to morphine was attenuated significantly in patients with depression. Neither the cortisol and prolactin response to morphine in the anorectic patients nor the cortisol response in the depressed patients we observed in this study suggests altered opiate receptor sensitivity. However, the decreased prolactin response to morphine in depressed patients remains compatible with this hypothesis. PMID- 2598476 TI - Free radicals and Graves' disease: the effects of therapy. AB - Plasma thiol (PSH), caeruloplasmin (CP), intracellular lysate thiol (LSH) and superoxide dismutase (SOD) activity were measured in 30 patients with newly diagnosed Graves' disease (GD). Compared to control subjects (C) PSH and SOD were significantly reduced (C vs GD, 507 vs 449 mumol/l, P less than 0.01; 2.1 vs 1.6 mumol/l, P less than 0.01 respectively) and LSH was significantly raised (C vs GD 181 vs 298 mumol/l). Treatment with carbimazole produced a significant rise in LSH and SOD. Propylthiouracil (PTU) treatment raised LSH levels but 131I treatment produced no significant change. All four parameters are involved in different ways in oxygen metabolism and together provide an indication of oxidative stress across the red-cell membrane. In addition LSH is a general radical scavenger and SOD a specific O2- scavenger. In Graves' disease the increased oxidative stress and increased general radical scavenging may result from raised free-radical activity. These changes, which have not previously been reported in Graves' patients, were modified by antithyroid drug therapy, but it is not clear whether this is a direct or indirect effect. PMID- 2598477 TI - Short-term fasting inhibits the nocturnal melatonin secretion in healthy man. AB - To investigate whether short-term fasting influences hormone release from human pinealocytes, nocturnal melatonin (MT) secretion was studied before and at the end of a 2-day fast in seven normal subjects (group A). Serum MT was measured every second hour between 1800 and 0800 h, and the nocturnal MT secretion, as reflected by the MT incremental area (MT area appearing above the 1800 h level), was calculated and compared before and during the fast. MT excretion by the urine (between 2200 and 0700 h) was also determined before, during, and after the period of food deprivation. Body weight and blood glucose concentration fell by 2.5 +/- 0.2 kg (mean +/- SEM, P less than 0.001) and 1.7 +/- 0.2 mmol/l (P less than 0.001) respectively during the fast. Nocturnal MT secretion declined by 19 +/- 3% (P less than 0.002), in contrast to urinary MT excretion which remained unaffected. In order to prevent blood glucose from falling significantly during the period of food deprivation, six additional normal subjects (group B) were given eight small oral doses of glucose (each dose 0.5 g/kg) at regular intervals during the 2-day fast. This did not prevent a weight loss (2.1 +/- 0.5 kg, P less than 0.01) of similar magnitude as in group A, but it restored a normal nocturnal MT secretion. The fact that glucose supplementation during fasting returns a decreased MT secretion to normal suggests that human pinealocytes require a certain minimal glucose delivery to function normally. PMID- 2598479 TI - Correction of low circulating levels of 1,25-dihydroxyvitamin D by 25 hydroxyvitamin D during reversal of hypomagnesaemia. AB - The effect of 25-hydroxyvitamin D (25OHD), given orally during the reversal of hypomagnesaemia, was studied in five patients with hypomagnesaemic hypocalcaemia and low serum levels of 25OHD and 1,25-dihydroxyvitamin D (1,25(OH)2D). The results were compared to those obtained in five other patients with similar initial levels of magnesium, calcium, 25OHD and 1,25(OH)2D who did not receive 25OHD. Serum levels of 1,25(OH)2D in the ten hypomagnesaemic patients were lower than in ten control subjects with low serum levels of 25OHD. The reversal of hypomagnesaemia was similar in the two groups of patients and elicited a similar increase of circulating iPTH levels. The expected increase of circulating 25OHD was observed in patients supplemented with 25OHD; their circulating 1,25(OH)2D rose within 48 h to normal levels, contrasting with the delayed and poor increase of 1,25(OH)2D in patients receiving no 25OHD. The evolution of serum calcium was however identical in the two groups. Our results suggest that vitamin D deficiency was a significant factor leading to low circulating levels of 1,25(OH)2D in hypomagnesaemic hypocalcaemic patients. The biological consequences of low serum 1,25(OH)2D in these patients remain unclear, but clearly, normal levels of 1,25(OH)2D are not essential for the correction of hypomagnesaemic hypocalcaemia. PMID- 2598478 TI - Variable effects of RU 486 on endometrial maintenance in the luteal phase extended by exogenous hCG. AB - This study was designed to assess the features and conditions for endometrial bleeding induction with the synthetic antiprogestin and antiglucocorticoid RU 486 during hCG-induced prolongation of the luteal phase. Eighteen healthy, surgically sterilized women and another five women with an intrauterine contraceptive device (IUD) participated. All subjects received hCG which was injected daily in increasing doses (500 to 15,000 IU) from day 9 to day 15 of the luteal phase. Ten subjects received hCG alone, and groups of three to 16 subjects received hCG combined with RU 486 (25, 50, 100, 200 or 400 mg/day). RU 486 administration was commenced on day 12 following the LH surge and given either for 1, 4 or 7 consecutive days. In certain cycles, tamoxifen (20 mg/day) was given for 4 consecutive days with hCG, or with hCG and RU 486. All treatment cycles were separated by one or two resting cycles. Frequent blood samples were taken to monitor the endocrine response. Treatment with hCG alone or with the various combinations of RU 486 produced similar serum levels of oestradiol and progesterone which were equivalent to those observed during early pregnancy. With hCG alone, the onset of bleeding was on day 21-24 after the LH surge, coinciding with the drop in oestradiol and progesterone. With RU 486 doses of 50 mg/day or more, an early bleeding episode almost invariably occurred on day 14-17 after the LH surge in the presence of high circulating steroid levels. In contrast, 25 mg/day RU 486 for 4 days failed to induce this early onset of bleeding in three out of six cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598480 TI - Abnormalities of thyrotrophin (TSH) evening rise and pulsatile release in haemodialysis patients: evidence for hypothalamic-pituitary changes in chronic renal failure. AB - Using a sensitive enzyme amplified immunoassay for TSH, the evening rise and pulsatile release of TSH were studied in 10 men with chronic renal failure treated by haemodialysis. Compared to euthyroid male controls the evening rise of TSH was attenuated (median 0.066 vs 0.195 mU/l/h, P less than 0.01) and the rate of rise correlated with the TSH response to TRH (r = 0.93, P less than 0.001). All subjects showed TSH pulsatility in at least one method of data analysis but the less sensitive incremental method showed no significant difference in pulse frequency and amplitude between the two groups. However, with time series analysis, periodicity was shorter (median 45 vs 95 min, P = 0.013) and pulse amplitude smaller (median 0.06 vs 0.175 mU/l, P = 0.017) in renal patients. Pulse amplitude, but not periodicity, correlated with the TSH response to TRH (r = 0.68, P less than 0.05). In addition, serum total thyroxine, free thyroxine and free triiodothyronine concentrations were reduced, while serum prolactin and 17 beta-oestradiol concentrations were raised. These changes in TSH evening surge and pulsatile release may contribute to the reduction in thyroidal hormone concentrations seen in renal failure and emphasize the value of sensitive methods of hormone and pulse data analysis. PMID- 2598482 TI - Impact of medical genetics on public health. Accomplishments, present state, and practical future possibilities. Proceedings of a symposium. 28-29 October 1988, Copenhagen. PMID- 2598481 TI - Studies of two thyrotrophin-secreting pituitary adenomas: evidence for dopamine receptor deficiency. AB - Of 22 previously reported patients with TSH-secreting pituitary adenomas challenged with dopamine agonists, 18 showed no decrease in serum TSH. There have been few in-vitro studies of these rare tumours so the mechanism of the dopaminergic resistance has remained obscure. We describe two further patients with thyrotrophinomas; the first was thyrotoxic (T3 6.1 nmol/l, TSH 7 mU/l) and the second was diagnosed after radioiodine for presumed Graves' disease. The second patient had an alpha-subunit: TSH molar ratio less than unity (0.27). In vivo TSH responses to TRH, bromocriptine and domperidone were compared with those of the resected tumour cells in vitro, the latter studied using a continuous perifusion system. Dopamine receptors were sought in membranes from each tumour using a radioreceptor assay employing 3H-spiperone. Patient 1 showed significant increases in serum TSH (7 to 13 mU/l) and alpha-subunit (18.7 to 385 ng/ml) after 200 micrograms TRH (i.v.) but patient 2 showed no such increases (TSH: 69 to 72 mU/l, alpha-subunit: 4.9 to 5.2 ng/ml). Neither patient showed a change in serum TSH following bromocriptine 2.5 mg (orally) or domperidone 10 mg (i.v.), though serum PRL responded normally. Serum TSH from patient 1 was of apparently normal molecular size but increased bioactivity (B/I ratio 3.8) and that from patient 2 was of increased molecular size but reduced bioactivity (B/I ratio 0.1). Tumour cells from each patient immunostained for TSH beta and alpha-subunit, and secreted TSH in vitro. The first showed dose-dependent TSH release after TRH (1 100 ng/ml) which could not be inhibited by dopamine (5 mumol/l) but the second was unresponsive to TRH in vitro. Neither tumour showed inhibition of TSH release by dopamine (5 mumol/l) or bromocriptine (0.01-10 nmol/l) and neither contained membrane-bound dopamine receptors. The results suggest that the dopaminergic resistance typical of most TSH-secreting pituitary adenomas may be due to altered or absent membrane-bound dopamine receptors. PMID- 2598483 TI - The prevention of thalassemia in Sardinia. AB - In this paper we review the characteristics and effectiveness of a program aimed at preventing homozygous beta-thalassemia in the Sardinian population. The target population for screening were couples at marriage, conception or early pregnancy. Awareness of the problem and the involvement of the population were achieved via the mass media or by personal approaches through lectures or discussions. Parents' Associations were consulted and have made themselves available to prospective couples in several critical areas. Education on thalassemias was introduced into the school curriculum. Counseling was based on private interviews at which the several options available were discussed with the individual carrier or the couples. Prenatal diagnosis was chosen by the large majority of couples counseled. The introduction of 1st trimester diagnosis resulted in a striking increase of the acceptance rate from 93.2 to 99.1%. Prenatal diagnosis was carried out initially by fetal blood analysis and thereafter by trophoblast or amniocyte DNA analysis. Direct detection of the mutation by oligonucleotide hybridization on agarose gel separated DNA fragments or by dot-blot analysis with allelic specific oligonucleotide probes on enzymatically amplified DNA was used. This program resulted in a decline in thalassemia major births of 90%. The reasons for residual cases were mostly lack of information and, less frequently, misdiagnoses or refusal of fetal diagnosis. PMID- 2598484 TI - Impact of medical genetics concerning phenylketonuria: accomplishments, status and practical future possibilities. AB - Millions of newborn infants are screened for phenylketonuria (PKU) to prevent the inherited metabolic error by dietary treatment. For some PKU patients a relaxed low-phenylalanine diet will be lifelong. PKU-women must return to a strict low phenylalanine diet before conception and during pregnancy to insure the delivery of a normal child. Two mutations that account for 60% of the PKU genes in Denmark are established and oligonucleotide probing enables carrier detection and genetic counselling. Primary hepatocytes can be successfully cultured and transformed with phenylalanine hydroxylase cDNA and somatic gene therapy of PKU may be a future possibility. PMID- 2598485 TI - Preclinical evaluation of terbinafine in vivo. AB - The fungicidal activity of terbinafine which has been demonstrated in vitro for several strains of dermatophyte, filamentous and dimorphic fungi, has been demonstrated in vivo in model systems for dermatophytoses. This activity is accompanied by a fast onset of action which leads to superior antifungal efficacy when compared with fungistatic drugs. PMID- 2598486 TI - Once daily administration of terbinafine to guinea-pigs with experimental dermatophytosis. PMID- 2598487 TI - A flow cytometric study of actinic reticuloid. AB - Potential progression of actinic reticuloid to malignant lymphoma was studied by DNA flow cytometry of affected formalin-fixed skin from six patients with histological and photobiological evidence of actinic reticuloid. DNA aneuploidy was absent in all patients providing no evidence that actinic reticuloid is a premalignant condition. PMID- 2598488 TI - Infundibular keratosis--a prototype of benign infundibular tumours. AB - Three cases of a benign follicular tumour of infundibular origin are reported. The neoplasms were solitary, verrucous, slowly-growing papules or nodules on the face, which were diagnosed clinically as verruca vulgaris or seborrhoeic keratoses. Histologically, several epithelial lobules were seen, mainly above the level of the surface of the surrounding skin, with characteristic funnel-shaped invaginations. The tumours occasionally contained vellus hairs or were connected with sebaceous glands and/or hair follicles at their bases, indicating their follicular origin. The tumour masses consisted of peripherally arranged basaloid and inner squamoid cells. The latter cells contained more glycogen and appeared paler with haematoxylin and eosin (H&E) stains than the normal inter-follicular squamous cells. Neither clear cells nor squamous eddies were observed. Palisading of the basaloid cells was not a prominent feature. The name 'infundibular keratosis' is proposed for such tumours, which probably represent the prototype of infundibular tumours of the hair follicle. PMID- 2598489 TI - Bullous lichen planus and lichen planus pemphigoides--clinico-pathological comparisons. AB - Two patients with lichen planus pemphigoides and two with bullous lichen planus were compared. Lichen planus pemphigoides was clinically distinguished by a more generalized lichen planus, more extensive blistering, the need for systemic corticosteroids and by a longer course. The blister of bullous lichen planus was a subepidermal bulla showing degeneration of the epidermal basal layer and other features of lichen planus, whereas in lichen planus pemphigoides the bulla was similar to that of bullous pemphigoid albeit with rather more neutrophils than are usually seen. Direct immunofluorescence was positive in lichen planus pemphigoides and negative in bullous lichen planus. Lichen planus pemphigoides and bullous lichen planus are separate entities: the former is an auto-immune disease precipitated by lichen planus and not related to bullous pemphigoid, the latter is probably not auto-immune but represents the extreme consequence of the lymphoid infiltrate at the dermo-epidermal junction. PMID- 2598491 TI - Urethral fistula and sinus formation in hidradenitis suppurativa. AB - Two patients with severe hidradenitis suppurativa are reported. In Case 2, with widespread and superficial disease without communication with internal organs, there was a good response to intensive surgical intervention. In the patient with hidradenitis suppurativa and urethral fistula formation adequate surgical treatment was not technically feasible and treatment had to be continued for at least 2 years without permanent cure in sight. A search of the literature confirms that this differentiation is important as the cases with fistulous involvement of internal organs tend to have a bad prognosis. PMID- 2598490 TI - Induction of hair growth in alopecia totalis with diphencyprone sensitization. AB - The therapeutic use of the induction of an allergic contact sensitivity to diphencyprone in alopecia areata has been studied. Fourteen subjects had alopecia totalis and four had extensive and long-standing alopecia areata. Topical diphencyprone was capable of inducing an allergic contact sensitivity in 16 subjects (89%), and 13 of these agreed to proceed to repeated intermittent applications to the left side of the scalp, the right side acting as an untreated control; six subjects achieved cosmetically useful regrowth of normally pigmented terminal hair. No clinical features seemed to distinguish those who showed a favourable response from those who did not. PMID- 2598492 TI - Treatment of peripheral gangrene due to systemic sclerosis with intravenous pentoxifylline. AB - Vascular problems are very common in systemic sclerosis with 95% of patients suffering with Raynaud's phenomenon at some stage in their illness. Acute ischaemic lesions are much less common, but when they occur are a serious complication, and are often difficult to treat. Many drugs have been used in this situation, including both oral and intravenous vaso-dilators and low molecular weight dextran, each with varying degrees of success. The phospho-diesterase inhibitor, pentoxifylline, is reported to be useful in peripheral vascular disease, and in Raynaud's phenomenon, and the intravenous form is indicated for acute peripheral ischaemia, though its use in the context of connective tissue disease has not so far been reported. We now report the use of intravenous pentoxifylline in two patients with acute peripheral gangrene due to systemic sclerosis. PMID- 2598493 TI - Subcorneal pustular dermatosis. AB - Subcorneal pustular dermatosis (SCPD) (Sneddon-Wilkinson disease) is a rare disorder. We present a case with classical clinical manifestations, and discuss the management of this disorder. PMID- 2598494 TI - Erythema ab igne affecting the palms. PMID- 2598495 TI - Transient post-inflammatory digitate keratoses. AB - We report details of two patients who had digitate keratoses as a transient phenomenon following inflammatory skin disorders. In one patient, keratoses arose from the epidermal surface, from invaginated pits in the epidermis, and from follicles. Apart from the short duration of the lesions, the clinical and histological features were similar to previously reported cases of digitate keratoses. PMID- 2598496 TI - Sarcoidosis presenting with multiple delled atrophic facial lesions. AB - We describe a patient who presented with multiple atrophic, delled erythematous facial lesions with surface scaling. Skin biopsy revealed a granulomatous histology, and a Kveim test was positive. Similar cutaneous lesions have not been previously reported in sarcoidosis. PMID- 2598497 TI - Vitiligo and nail dystrophy. PMID- 2598498 TI - First Symposium on Terbinafine (Lamisil). Held during the tenth congress of the International Society of Human and Animal Mycology. Barcelona, 1988. Proceedings. PMID- 2598499 TI - Liver-specific and high-level expression of human serum amyloid P component gene in transgenic mice. AB - To analyze the regulation of human serum amyloid P component (SAP) gene expression, we have produced seven transgenic mice. The 3.3 kb human SAP genes containing about 0.8 kb of 5' and 1.5 kb of 3' flanking region were injected into fertilized eggs of C57BL/6 mice. In five of the seven transgenic mice, human SAP was detected in the sera and serum concentrations were higher than that of human serum in three lines. The human SAP gene was expressed only in the liver. Amounts of human mRNA in the liver and serum concentrations of human SAP were roughly proportional to the copy number of the integrated gene. Human SAP production lowered the serum levels of mouse endogenous SAP. With the intraperitoneal administration of lipopolysaccharide, the mRNA levels in the liver and serum levels of mouse SAP increased several-fold in both the control and transgenic mice. On the other hand, neither the mRNA nor the serum levels of human SAP increased significantly. PMID- 2598500 TI - Tissue- and developmental stage-specific expression of the rat ornithine carbamoyltransferase gene in transgenic mice. AB - Rat ornithine carbamoyltransferase (OCT; EC 2.1.3.3) is encoded by a large gene of 75 kilobases. Expression of this gene is restricted to the liver and small intestine, and there is an increase in expression late in gestation. The recombinant gene carrying 1.3 kilobases of the 5' flanking region of the gene fused to the rat OCT cDNA was microinjected into fertilized eggs, and 17 transgenic mice were produced. Expression in the liver of the transgene was detected in three mice. In these mice, the transgene expression was observed exclusively in the liver and small intestine. Expression of the transgene in the intestine was comparable to that of the endogenous mouse OCT gene, whereas expression in the liver was much lower than that of the endogenous gene. The developmental pattern of expression of the transgene was similar to that of the endogenous gene. Therefore, the 5' flanking sequence of the rat OCT gene seems to be sufficient for the developmental and tissue-specific expression of the gene. An explanation for low expression in the liver remains the subject of ongoing study. PMID- 2598501 TI - [Documentation of hearing and speech function in patients with clefts of the lip, jaw and palate]. AB - Many different methods of documentation made an urgently needed comparison of various therapeutic models impossible. This situation demands a standardization of the documentation of treatment results in cleft palate patients. A basic documentation program for speech- and hearing-evaluations was drawn up. PMID- 2598502 TI - [Minimum documentation of clefts of the lip, jaw and palate. An interdisciplinary commission's proposal]. PMID- 2598503 TI - [Accuracy of apposition achieved by mandibular osteosyntheses. Stereophotogrammetric study]. AB - The accuracy of apposition achieved by wire and plate osteosyntheses is measured with the aid of close range stereophotogrammetry in the mandibles of dead bodies. Both osteosynthesis methods are characterized by an increase in the intercondylar distance which, on the average, is about 3.3 mm greater after plate osteosynthesis and about 1.9 mm after wiring. Moreover, osteosyntheses of the base of the mandible may involve a tendency of the condyle to become caudally dislocated. PMID- 2598504 TI - [Computer documentation of malignomas of the mouth, jaws and face using the BAIK system]. AB - The computer-supported documentation of head and neck tumors by means of the BAIK system is presented. The experience after introducing the project to clinical routine use in patient's treatment is outlined. The subsystems of BAIK are critically reviewed for this purpose. Although we realize some drawbacks of BAIK the system proved to be useful for our application, mainly because of its strong retrieval functions, combining coded and free text data manipulation. PMID- 2598505 TI - [Clinical, histological, and immunohistochemical studies of squamous cell carcinomas of the oral mucosa and the prolabium]. AB - In diagnosing and monitoring squamous cell carcinomas of the oral mucosa and the prolabium the carcinoembryonic antigen (CEA) is a frequently used tumor marker. In a pilot study six of these carcinomas with established pathological serum levels of CEA were clinically analyzed and immunohistochemically examined for the tumor antigens CEA and, in addition, TPA (tissue polypeptide antigen). Only in one case could a positive CEA reaction be found. In the same tumors TPA could not be demonstrated. It is concluded from these results that elevated CEA serum levels are no tumor specific reactions and that the use of this tumor marker is to be considered with criticism. PMID- 2598506 TI - [Oral and maxillofacial tumors and chronic alcoholism. Need for a holistic treatment approach from psychological point of view]. AB - History taking and careful clinical examination reveal alcohol addiction in a great number of the patients with tumors of the lips, oral cavity and oral pharynx. Alcohol, as a cocancerogenic, is not only an important factor in the development of tumors of the upper digestive tube and the respiratory tract, but, as a habit-forming agent, may also present considerable problems for the affected patients. Hence the treatment plan was extended to include additional psychological aspects of the management of the disease and the problems of addiction. The psychological objectives are described and first results of this extended treatment concept are reported. PMID- 2598507 TI - [Maxillary antrum surgery with or without bone lid formation. Retrospective comparative study]. AB - A long-term study was performed after conservative maxillary antrum surgery with (50) and without (106) bone lid formation including a total of 154 patients. While no differences were found regarding the patients' sensitivity to changes in the weather, neurological disorders, or complaints of pressure sensations, considerably better results were obtained with respect of the time until a stable postoperative condition was achieved, the radiographic and the local findings, after surgery with the use of a bone lid. PMID- 2598508 TI - [Thermoprofile analysis of the face for diagnosing trigeminal nerve lesions]. AB - In the framework of differential diagnosis thermography as a non-invasive method has gained in importance. 34 patients suffering from lesions of the trigeminal nerve were examined by our method of thermoprofile analysis of the facial skin. In those lesions where perception disorders were dominant hypothermia occurred, while those lesions where pain was preponderate showed hyperthermic changes. The temperature of the facial skin, however, only shows a small difference compared to the skin of the trunk and the extremities. Therefore, our method of thermoprofile analysis should not be used as a single diagnostic test but as an objective screening procedure for nerve lesions in the facial area. PMID- 2598509 TI - [Introduction of diagnostic statistics in accord with section 16 of the Federal Ordinance for Hospitalization Cost Rates (BPflV). Basic documentation for the clinical branch of oral and maxillofacial surgery]. AB - In 1984 a first diagnosis and treatment code was developed for the computer documentation of patient data at the clinical department for oral and maxillofacial surgery of the Munster University Hospital. After a long time of testing and improving in day-by-day practical use, it today includes a total of 126 diagnoses and 169 forms of treatment. When in 1986 the Federal Ordinance for Hospitalization Cost Rates came into power, this documentation system had to be re-coded to comply with ICD 9 and, at the same time, a documentation sheet had to be developed that would meet both the necessary scientific standards and the given administrative criteria. In this paper a documentation sheet is presented that fulfills both requirements and, by virtue of its simplicity, avoids almost any loss of data. PMID- 2598510 TI - [Comparative studies on stability of titanium and V4A osteosynthesis screws]. AB - Three years of clinical use and testing provided clear support to the advantages of the self-tapping titanium splithole screws. Although having rather flat heads these screws afford a fast grip with the screw driver blade. In addition to this, the pin offers good axial guidance and adhesion of the screw. The cylindrical design of the screw equator improves the fit of the screw in the chuck of the screw driver. The spherical shape of the lower half of the screw head increases the circular contact to the osteosynthesis plate, which is particularly favorable in the case of a minor angular error. PMID- 2598512 TI - [Experience with combined maxillary and mandibular osteotomies]. AB - Possibilities are discussed to achieve useful results for both alveolar ridges by combining standard procedures of orthopedic surgery used for single jaw operations. The 8 patients were not routine cases. The indications were based on several different reasons. 3 patients first got orthodontic treatment followed by surgery. In the other five cases orthodontics had been impossible for various reasons. All cases were treated with single stage procedures and did not relapse. PMID- 2598511 TI - [Partial characterization of the epithelial lectin binding sites of human gingiva and skin]. AB - Frozen sections of human gingiva and skin, fixed in acetone, were subjected to limited enzyme digestion (neuraminidase, proteinase K, trypsin) or, respectively, the application of solvents (chloroform/methanol, triton X-100) to allow a partial characterization of epithelial lectin binding sites. Gingiva differs from normal skin in that more conA-binding glycolipids are present in the lower cell layers. In the upper layers conA-fixing glycoproteins are prevailing. Psoriatic foci regularly exhibit an increased presence of conA-binding glycolipids. Gingiva and normal skin have some common features in the behavior of the lectin binding sites of HPA, WGA and UEA I. Analogies in the binding pattern of conA and UEA I in gingival tissue and in psoriatic foci are thus due to different lectin receptors. PMID- 2598513 TI - [Reasons for the neglect of orofacial and alveolar malignancies]. AB - In 1983 we treated 71 patients with orofacial and alveolar malignancies. In 25 cases the tumor had advanced beyond T2. An evaluation of their inpatient treatment data demonstrated that the lesion had been neglected by patient and physician. Our results clearly stress the need for information of the citizen and specialised postgraduate training of physicians and dentists about the early detection of orofacial malignancies. PMID- 2598514 TI - [Grading and prognostic rating of oral carcinomas based on their cloning potential in vitro. Guidelines for clinical antioncogram interpretation]. AB - Malignancies of the oral cavity are not an entity in terms of their clonal growth potential. The antioncogram which is used within the individual treatment concept against the carcinoma may be employed to determine whether the tumor of this patient has a high or low cloning potential. This parameter of differentiated cloning is an independent tumor characteristic for the purpose of grading and is closely related to clinical course and prognosis of the patient. Patients with highly cloning malignancies have a significantly shorter life expectancy than patients with the same risk factors suffering from carcinomas with a low cloning potential. PMID- 2598515 TI - [Risks of serial intramuscular injections]. AB - A recently reviewed case underlined the danger of serial intramuscular injections. More recent results about muscular response to injection treatment and its morphological, anatomical, and pathophysiological effects on muscular tissue are described. Our studies about the optimum length of the needle for intramuscular injections and the thickness measurements of tissue and fat layers in the area of the most important injection points (upper outer quadrant of Hochstetter point) were supplement by animal experiments to prove that the use of short needles might lead to subcutaneous misinjections causing acute drug-induced dermal embolism. On the other hand these animal experiments demonstrated that even correctly placed serial injections might cause severe necrosis of the deep muscular structures accompanied by a major increase in serum creatinin phosphokinase activity. With intragluteal serial injections one must think of repair-induced muscular fibrosis which led to an intragluteal implantation cyst in the case reviewed by us. PMID- 2598516 TI - [Influence of extensive information on readiness for surgery]. AB - 207 patients who already had had one lower wisdom tooth extracted surgically were interviewed about their readiness for accepting the same kind of surgery again. 9% of this cohort refused the repeated (fictitious) surgery. After extensive information about four serious post-/intraoperative complications 10%--only one percent more--now refused surgery. However, there were shifts within the "yes" and "no" groups. The overall outcome of this study whose figures may only be applied to other types of surgery with great reservations and care, demonstrate the trend that comprehensive and detailed information does not have any great influence on the attitude of the patient towards surgery. PMID- 2598517 TI - [A new concept for the reconstruction of the extremely atrophied mandible]. AB - The introduction of interposition techniques for mandibular ridge augmentation brought about such great improvement in the results that we may speak, with reservations, of having achieved absolute ridge augmentation at least in the anterior mandibular area. The unsatisfactory results in the buccal area induced us to change the treatment concept and study the patients treated according to this new concept in a first post-treatment evaluation. PMID- 2598518 TI - [State of the art of nerve fibrin adhesion]. AB - Although in use for over 15 years, commercially available fibrin adhesives are still regarded with scepticism when they are used for nerve anastomosing. We therefore studied the fibrosing potential of the two presently available fibrin adhesives by determining the amount of connective tissue in the anastomoses using light microscopy. In addition, regeneration was examined by electrophysiology. No significant differences were detected when 1000 KIE aprotinin and 3 IU thrombin were used. The amount of connective tissue was 33%, and regeneration was proven beyond doubt. PMID- 2598519 TI - [Intraoral soft tissue metastases of a renal cell carcinoma]. AB - Face, mouth and jaws represent seldom localisations of metastatic lesions. 5-20% of these lesions are reported with localisation in the maxilla, whereas 90% are found in the mandibula. Metastatic tumours in the oral soft tissue are very rare. The most common primary tumour seems to be the renal cell carcinoma. Only histological examination can give a differentiation against benign tumours. The diagnostic and therapeutic management of a 46 years old woman with a metastatic intraoral lesion of a renal cell carcinoma is presented. PMID- 2598520 TI - [Speech therapy for children with cleft lips and palates. I. Basic linguistic considerations]. AB - According to several basic principals of hermeneutic theory (theory of understanding natural languages) we describe the major fields of language acquisition in which anomalies of CPL children often can be found. Besides phonation and articulation there are morphological, psychomotoric, onomatopoetic, and isotopic disorders. Also a delay of understanding by listening is often observed. Additionally some cofactors in psychodynamics of the family have to be respected. Defense mechanisms, somatization, and social symptomatization are described. Some examples from statistics and experimental psycholinguistics show, that a diagnosis of early language acquisition can't be found by comparing means (naive model of diagnosis). We show how to find out the multiple covariance of early language acquisition tests with the control groups. A final case study shows a typical process of CLP children's language acquisition. PMID- 2598521 TI - [Recording of palatal growth under drinking plates in cases with wide palatal clefts]. AB - In 1987 eight children with complete wide palatal clefts were born in Berlin. The infants primarily received a drinking plate and maxillary impressions were taken routinely at three months intervals. In the casts a spontaneous narrowing of the clefts was observed. PMID- 2598522 TI - [Surgical correction of extreme prognathism]. AB - Extreme anomalies of alveolar bone and occlusion of any degree may be corrected surgically to achieve a satisfactory occlusion and a largely corrected and normalised profile. PMID- 2598524 TI - [Evaluation of the skin sympathetic function by the decrease of skin temperature at the finger tip immersed into cold water]. AB - The change of the skin temperature at the finger tip immersed into cold water was measured in normal volunteers and in patients with disturbances of various portions of sympathetic nervous system with copper-constant thermocouple. The skin temperature of the normal subjects decreased soon after the immersion, partly due to cooling by the cold water, and partly due to the decrease of the skin blood flow. The skin sympathetic activity recorded from three normal subjects using the technique of microneurography presented an increase during the decreasing phase of the skin temperature. The skin temperature of the patients who received stellate ganglion block did not fall and maintained higher level compared to that of normal subjects. These data indicated that the decreasing phase of the skin temperature of the immersed finger is related to the increase of skin sympathetic activity. Cases of vascular neuropathy (lesion in post ganglionic fiber), Shy-Drager syndrome and pure autonomic failure (lesion in pre ganglionic fiber), cervical spondylosis and cervical disc herniation (lesion in descending tract of sympathetic system in spinal cord), and bleeding in pons tegmentum (lesion in descending tract in brain stem) were examined and all of them presented poor decrease of the skin temperature during the immersion. The skin temperature decreased, but incompletely in the patients, who had suffered from thalamic infarct and post-central gyrus infarct, and did not feel any sense on the immersion. These results indicate that the decreasing phase of the skin temperature of the finger immersed into cold water depends more upon the efferent than upon the afferent system, and this test is useful for evaluation of the skin sympathetic function. PMID- 2598523 TI - Value of plasma NH2-terminal fragment of pro-opiomelanocortin in marking human lung cancer in various clinical settings. AB - Plasma concentration of amino-terminal segment of pro-opiomelanocortin (N-POMC) was measured by radioimmunoassay (RIA) in 144 patients with various forms of lung cancer during pneumonectomy, at different times of the day after being newly diagnosed and serially, throughout their treatment (surgery or chemotherapy) in order to assess its value as a biomarker in this disease. Normal volunteers, coal miners smoking but without known lung diseases, and the patients with diverse pulmonary disorders served as comparison groups. A significant transtumoral gradient of N-POMC was found at surgery in 15 of 57 (26%) patients. Subjects without lung afflictions had significantly lower N-POMC levels than patients with pulmonary diseases (benign or malignant) only when the blood was drawn before breakfast. Furthermore, fasting levels in all subgroups of patients were higher at any time of the day than nonfasting ones. Finally, N-POMC levels did not decrease significantly after successful treatment of lung cancer (by surgery or chemotherapy) but were markedly higher after relapse. These results suggest that N-POMC, despite the fact that it cannot be used to discriminate lung cancer patients from controls, is a biomarker which may predict relapse in patients successfully treated by chemotherapy for their pulmonary neoplasm. PMID- 2598525 TI - [Acute disseminated encephalomyelitis affecting medulla and upper cervical cord- comparison of the clinical signs and MRI findings]. AB - Correlation of MRI abnormalities and clinical manifestations was studied in a case of acute disseminated encephalomyelitis. A 54-year-old man developed Brown Sequard syndrome affecting the right upper cervical cord, bilateral bulbar palsy, right Horner syndrome, and rotatory nystagmus. After the admission, right facial numbness and weakness of left upper and lower limbs were added. He was treated with glucocorticosteroid successfully. Painful tonic seizures of left upper and lower limbs were noted in the convalescence. T1-weighted MRI of the brain and spinal cord revealed low signal intensity areas in the medulla oblongata and right upper cervical cord. T2-weighted images showed a high signal intensity in the same areas. The distribution of MRI abnormalities well corresponded to the clinically expected lesions. The MRI abnormalities gradually decreased and disappeared with his recovery. The MRI abnormalities appeared to reflect edema accompanying the acute inflammatory process. MRI seems to be a very useful test for verifying lesions in the brainstem and spinal cord in a case of acute disseminated encephalomyelitis. PMID- 2598526 TI - [Three patients with hypopituitarism accompanied by primary empty sella presenting mental symptoms]. AB - We report here three patients with hypopituitarism accompanied by primary empty sella, whose first manifestations were various mental symptoms. Endocrine studies revealed that two patients showed panhypopituitarism and the other had isolated adrenocorticotropin (ACTH) deficiency. Although several different types of pituitary dysfunctions have been described in a mild form, empty sella is usually asymptomatic. Their first manifestations were mental symptoms; consciousness disturbance, psychomotor agitation, visual hallucination and delusion. Isolated ACTH deficiency is an uncommon disease which etiology is still undetermined. A case with isolated ACTH deficiency associated with an empty sella has been reported before. It is suggested that empty sella might have a role in pathogenesis of isolated ACTH deficiency. The empty sella was confirmed by metrizamide cisternography and magnetic resonance imaging (MRI). These imaging studies are good tools to disclose empty sella. Replacement with cortisone and levothyroxine resulted in an improvement in the mental symptoms in two patients with panhypopituitarism. No alteration was observed following cortisone administration in the patient with isolated ACTH deficiency. Delusion and visual hallucination in this patient poorly responded to treatment with neuroleptics. PMID- 2598527 TI - [A case of multiple sclerosis with polyradiculitis and spinal subarachnoid block]. AB - A case of 53-year-old female with multiple sclerosis was reported. In August 1987, she suffered from weakness in her legs and urinary retention. These signs had progressed with incomplete remissions and exacerbations. In March 1988, she developed sensory loss of all modalities below C2 level, spastic paralysis of upper extremities and flaccid paraplegia of lower extremities. Electromyography showed evidence of denervation in affected muscles of all extremities and paraspinal muscles. On lumber puncture, spinal fluid pressure fell to 0 mmH2O after removal of the spinal fluid of 12 ml, and the CSF protein was 740 mg/dl, indicating subarachnoid space block. The oligoclonal band was positive. MRI showed swelling in the cervical and upper thoracic cord, and multiple lesions in the periventricular white matter in the cerebrum. We diagnosed this case as multiple sclerosis in combination with acute polyradiculitis. The spinal subarachnoid block was considered to be caused by the swelling of the spinal cord. PMID- 2598528 TI - [A case of Wyburn-Mason syndrome]. AB - A extremely rare case of unilateral retinocephalic vascular malformation (Wyburn Mason syndrome) was reported. A 5 year-old girl was seen to a ophthalmologist complaining of exophthalmus of her left eye after trauma on her face for the past 2 months. On ophthalmologic examinations, retinal arteriovenous malformation was recognized in her left eye and she was referred to neurosurgical service for the evaluation on occurrence of traumatic carotid cavernous fistula. Plain CT did not show any abnormality but enhanced CT revealed an abnormally enhanced lesion in the thalamus and basal ganglia and along to the left optic nerve. Left carotid angiography and vertebral angiography revealed a huge arteriovenous malformation in the left thalamus and basal ganglia extending to the left orbita. The arteriovenous malformation was fed from the C3 segment of the carotid artery, anterior, middle and posterior cerebral arteries, and drained to the internal cerebral vein and basal vein. The intraorbital part of the malformation was mainly fed from the external cerebral artery. She was diagnosed as Wyburn-Mason syndrome. We stressed in the paper that enhanced CT was useful for the diagnosis of the Wyburn-Mason syndrome. PMID- 2598529 TI - [CT evidence of high density area in bilateral striatum secondary to anoxia]. AB - We recently observed a patient in whom basal ganglia calcification (BGC) was demonstrated on sequential CT scans only 9 days after the anoxic episode. A 58 year-old woman had a history of diabetes mellitus for 23 years for which she was treated with insulin. She had a operation for retinal detachment under local anesthesia. Two days after the operation, she developed dyspnea, and was referred to our department. She was intubated, and respiratory support was begun. On neurological examination, she was semicomatose, and intermittent spontaneous movements involved in all extremities. The pupils were 3 mm in diameter, equal and responsive. Full doll's eye responses were obtained both horizontally and vertically. Deep tendon reflexes were hyperactive bilaterally without ankle jerks and extensor plantar responses. Arterial blood gas levels revealed a PaO2 of 49 mmHg, PaCO2 38 mmHg: pH 7.16. Serum Ca, P, Mg, Al-p and parathyroid hormone levels were normal. The EEG was isoelectric. Although the initial CT scan was normal, the subsequent CT scan 9 days later showed extensive high density change of the striatum, which was assumed to be BGC due to anoxia was briefly discussed. PMID- 2598530 TI - [Spastic paraplegia in Sjogren's syndrome associated with mixed connective tissue disease (MCTD)--a case report]. AB - A case of spastic paraplegia in Sjogren's syndrome associated with mixed connective tissue disease is reported. In this 49-year-old woman spastic gait and arthralgia developed at the age of 23 years and progressed chronically. On neurologic examination, supranuclear paresis of facial nerve was observed. Deep tendon reflexes were hyperactive in the jaw, upper and lower extremities. Serological tests showed that anti-nuclear, anti-RNP, and anti-SS-A antibodies were positive. Spinal fluid analysis showed that rate of de novo central nervous system (CNS) IgG synthesis was increased, and C3/C4 ratio was elevated. CT scans of the brain showed calcifications at bilateral basal ganglia, dentate nucleus and cerebellar vermis. An electroencephalogram revealed diffuse slowing, and 123I IMP brain scans revealed decreased cerebral blood flow. MRI of brainstem and cervical cord were normal. These findings suggested that corticospinal tracts upper the brainstem were severely affected, and that there were multifocal latent lesions in the CNS. Mechanisms of the CNS involvement were supposed to be both autoimmune abnormality in the CNS, and vascular impairment. PMID- 2598531 TI - [Korsakoff's syndrome as a prominent feature of bilateral paramedian thalamic infarction--a case report]. AB - We reported the first Japanese case of bilateral paramedian thalamic infarction associated with prominent Korsakoff's syndrome. 53-year-old man suffered from semicoma on the morning of September 16th, 1988. After recovery of consciousness disturbance, neurological examination revealed vertical eye gaze palsy, areflexia of lower extremities, apathy with hypersomnia and amnesia. Amnesia was accompanied with prominent confabulation, disorientation and lack of insight into his own disability. While X ray-CT revealed only ambiguous low density area in the bilateral thalamus, MRI of horizontal section by short spin echo revealed symmetrical low signal area restricted in the paramedian area of bilateral thalamus, and that of coronal section revealed characteristic butterfly-shaped lesion. Left BAG revealed that both posterior thalamoperforating arteries showed type 3 variation of Percheron's classification which arisen from artery arcade bridging between both side of interpeduncular segment of posterior cerebral artery. He showed gradual improvement in apathy with hypersomnia and disorientation but not in Korsakoff's syndrome nor ophthalmoplegia. PMID- 2598532 TI - [A comparative study between amyotrophic lateral sclerosis patients with and without mechanical ventilation]. AB - Fifty-three patients with amyotrophic lateral sclerosis (ALS) were examined as to duration of illness, cause of death and need for respirator assistance. In 47 patients with ALS, respiratory failure is the most common cause of death accounting for 62% of all fatalities. Eleven patients with mechanical ventilation died of pneumonia and respiratory failure in four cases, atelectasis, gastrointestinal bleeding and asphyxia in one. Thirteen of 53 patients with ALS required mechanical ventilation. Six cases were put on a volume-limited respiratory or a pressure-limited respirator with O2 blender, and seven cases were put on a pressure-limited respirator only, which was unable to control oxygen concentration. As to the duration of their illness, patients with mechanical ventilation survived significantly longer than those without mechanical ventilation, so patients using a respirator could expect to live significantly longer than those without one. Patients using a volume limited respirator or a pressure-limited respirator with O2 blender had significantly longer duration of mechanical ventilation than those using a pressure-limited respirator only. It is concluded that a volume-limited respirator or a pressure limited respirator with O2 blender is useful, if mechanical ventilation is needed, for ALS patients presenting with respiratory failure. PMID- 2598533 TI - [Chronic recurrent-progressive polyradiculoneuritis--Characteristics of autonomic dysfunction]. AB - We examined autonomic dysfunctions in 12 patients with chronic-recurrent progressive polyradiculoneuritis (C-R-P-PRN), consisting of 6 males and 6 females with the clinical duration of 8 months to 16 years, and with the age ranged 13 and 71 years. Sixteen healthy volunteers, aged 20 to 70 years, were also examined. Thermal sweat rate was recorded on the palm, forearm, upper arm, anterior chest, lateral thigh and lateral aspect of lower leg using a ventilated capsular method in a climatic chamber at 40 degrees C and 40% of relative humidity. After steady state was attained, thermal sweat rate was measured. Local sweating induced by intradermal injection of pilocarpine and nicotine (a concentration of 10(-4), 0.1 ml) was also measured on the forearm and lower lateral leg at 23 degrees C of room temperature and 40% of relative humidity. Other autonomic functions including skin temperature at rest and after cold loading (15 degrees C, 6 minutes), variation in the R-R interval (CV%), pupillary function (response to 1.25% epinephrine, 2(-5) pilocarpine, 5% tyramine), orthostatic hypotension and bladder dysfunction were also monitored. A decrease in sweat rate and recovery rate of skin temperature was seen more frequently in patients with C-R-P-PRN than normal volunteers. Abnormality in the thermal sweat rate and local sweat response against nicotine and pilocarpine was present more frequently in the forearm and distal leg as compared with the chest and thigh.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598534 TI - [Clinical characteristics of painful dystonic foot response in patients with Parkinson's disease]. AB - We analyzed clinical characteristics of painful dystonic foot response (PDFR) which was observed in 7 patients with Parkinson's disease during levodopa therapy. PDFR was divided into 3 types, (1) early morning type (2) end of dose type (3) peak dose type, according to the serum levodopa concentration and clinical picture. Four patients showed different type of PDFR during observation. Provocative factors included stimulations to sole such as sacking or standing, abrupt change of mode of levodopa administration. Clonazepam ameliorated markedly the frequency and severity of PDFR in 3 out of 4 patients. Several trials to reduced fluctuation of the serum levodopa concentration such as fractionation into small doses and frequent administration, and to use of levodopa alone instead of dopa-decarboxylase inhibitor combined tablet, failed to show improvement and gave rather transient aggravation. For the control of PDFR most important thing was the reduction of dosage of levodopa. The efforts to avoid the above provocative factor are also needed. If the patient suffered from the frequent PDFR attack, the PDFR ameliorating drugs such as clonazepam would be useful. PMID- 2598535 TI - [Metastatic brain tumor in the elderly]. AB - Authors have reviewed 322 consecutive patients with malignant tumors confirmed by pathological studies between October 1973 and August 1987 in order to determine the frequency, clinical presentation, and lesion localization of metastatic brain tumor in the elderly. Among 322 patients with malignant tumor, 7 patients with primary brain tumor and 21 patients with metastatic brain tumors were found. The over-all frequency of metastases to the brain was 5.8%. This frequency of brain metastasis in the elderly was lower than those of the previous literature which have varied from 9 to 35%. The patients' ages with metastatic brain tumor ranged from 65 to 88 years with a median age of 77.5 years. The primary tumor sites of metastatic brain tumors were limited to 5 kinds of organs. These metastases were found in 27.3% of 11 patients with breast cancer, 17.5% of 80 patients with lung cancer, 6.7% of 15 patients with bile duct system cancer, 5.0% of 20 patients with pancreatic cancer, and 2.0% of 91 patients with gastric cancer. There was no brain metastasis in the other kinds of carcinoma. Among 21 metastatic brain tumors, there were 14 patients with lung cancer, 3 patients with breast cancer, 2 patients with gastric cancer, 1 patient with cholangiocarcinoma, and 1 patient with pancreatic cancer. In this series, the frequency of single and multiple metastases were 13 and 8 cases, respectively. The multiple brain metastases ranged from 2 to 6 nodules. In 21 metastatic brain tumors, there were 42 metastatic nodules in total.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598536 TI - [A study of mitochondrial electron transfer chain in myotonic dystrophy]. AB - Ragged-red fibers (RRFs) are mainly seen in mitochondrial myopathy and related to biochemical defects in electron transfer chain on some occasions. Recently, some papers reported the occurrence of RRFs in the biopsied muscle of myotonic dystrophy (MyD). To examine whether the mitochondrial function is disturbed in MyD, we have studied the biopsied muscles of 12 cases with MyD (10 males and 2 females averaging 38 years of age) morphologically and mainly biochemically. RRFs, ranging from 2--20% of the muscle fibers, were identified in 5 out of 12 cases. On electron microscopy, these fibers had aggregated abnormally enlarged mitochondria with dene bodies, concentrically whirled membranous cristae and paracrystalline inclusions. Clinically, 4 of 5 cases with RRFs had mild to moderate and only 2 of 7 without RRFs had ophthalmoplegia. Bicycle ergometer exercise test showed abnormal increase of lactate/pyruvate ratio in three cases with RRFs. Histochemically, cytochrome c oxidase (CCO) activity was absent selectively in all of the RRFs. Immunohistochemical staining showed the presence of CCO protein by using monoclonal antibody which was specific to CCO subunit IV. Biochemical study with crude muscle extract of 11 cases of MyD showed decreases in NADH dehydrogenase, NADH CoQ reductase, succinate CoQ reductase (SCR), CCO, carnitine actyl transferase activities in most of cases regardless RRFs. To avoid the influence possibly derived from the various stages of muscle degeneration in the biopsied specimens, we calculated the ratio of the enzyme activities compared with succinate dehydrogenase which was located in the electron transfer chain and did not show any statistical difference regardless of RRFs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598537 TI - [A nosological study of a patient showing ataxia & lower motor neuron involvement]. AB - A sporadic case of spinocerebellar degeneration with prominent involvement of the motor system has recently been encountered. A 54-year-old man without family history noticed speech disturbance at the age of 46 and weakness in his right hand the following year. The muscle weakness and atrophy were slowly progressive and made walk impossible at the age of 50, when his dysphagia increased. At the age of 54, he was admitted to our hospital when neurological findings revealed marked amyotrophy of general skeletal muscle and tongue with fasciculation. Deep tendon reflexes were decreased. Cerebellar ataxia was impossible to evaluate because of profound muscle weakness. And sensory disturbance was suspected in the distal portion of the lower extremities. CT scan revealed progressive atrophy of the brain stem and cerebellum. The patient died at the age of 54 due to CO2 narcosis. The clinical course was 8 years. A summary of the pathological findings was as follows: 1) Marked neuronal loss of the anterior horn of the spinal cord and motor cranial nerve nuclei except for oculomotor nuclei, with mild degeneration of pyramidal tract below lumbosacral level. 2) Degeneration of cerebellipetal system, spinocerebellar tract, Clarke's column and the middle root zone and cerebellifugal system, dentate nucleus, superior cerebellar peduncles, and red nucleus. 3) Mild degeneration of pontine nuclei, inferior olivary nuclei, pontine transverse fibers, the middle and inferior cerebellar peduncles, cerebellar white matter and Purkinje cells as in OPCA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598538 TI - [Correlation of clinical course with MRI findings in olivo-pontocerebellar atrophy and late-cortical cerebellar atrophy]. AB - We quantitatively analyzed 1.5 T MRI in 36 cases of sporadic spinocerebellar degeneration (SCD) and 30 control cases without intracranial lesions, using graphic analyzer. SCD consisted of 21 olivo-ponto-cerebellar atrophy (OPCA) and 15 late cortical cerebellar atrophy (LCCA). There was negative correlation between vermian size and the duration of illness both in OPCA (r = 0.8960, p less than 0.001) and LCCA (r = 0.7756, p less than 0.01), but the progression rate in OPCA was three times greater than that in LCCA. LCCA was suggested the preclinical vermian atrophy by the statistical regression study. In OPCA, the duration of illness also revealed significant correlations with atrophy of ventral pons (r = 0.8308, p less than 0.001) and also cerebellar hemisphere (medial hemisphere; r = 0.7278, p less than 0.001. lateral hemisphere; r = 0.6039, p less than 0.01). OPCA showed diffuse atrophy of cerebellar hemisphere, whereas LCCA showed medial dominant atrophy. OPCA demonstrated significant correlation between the fourth ventricle dilatation and the duration of illness (r = 0.6005, p less than 0.01). A discriminant study significantly separated OPCA, LCCA and control each other by sizes of ventral pons and cerebellar vermis (p less than 0.001). In T2 weighted MRI, 10 cases out of 14 LCCA did not show hypointensity in dentate nucleus in spite of normal appearance in the other portions usually decreased intensity. The dentate nucleus of OPCA showed a significant atrophy. The incidence of putaminal hypointensity in OPCA was significantly greater than that of control group (chi-square = 6.476, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598539 TI - [A case of recurrent multiple cerebral infarctions with protein C abnormality]. AB - A 38-year-old man of recurrent episodes of multiple cerebral infarctions with protein C abnormality was reported. He had six episodes of visual disturbance within a year. The neurological examination revealed bilateral visual loss and impaired visual field except for small central area. However, there were no abnormalities in the deep tendon reflexes and muscle strength of all extremities and cerebellar examinations. CT scan revealed multiple low density areas in the bilateral posterior lobes, and cerebral angiography demonstrated the severe stenosis of the ganglionic portion and the supraclinoid portion of the right internal carotid artery. Plasma levels of antithrombin-III activity, plasminogen activity, protein C activity, protein C antigen and protein S antigen were 105, 106, 28, 166 and 120%, respectively. Because only protein C activity decreased markedly, a diagnosis of protein C abnormality was established. We started warfarin therapy under the administration of concentrates of factor IX complex, since then there has been no cerebral accident. PMID- 2598540 TI - [A case of Becker type congenital myotonia with myalgia]. AB - We reported a case of Becker type congenital myotonia with myalgia. A 28 year-old woman admitted to our hospital because of right anterior chest pain and back pain. She was diagnosed as myotonic dystrophy by other university hospital when she was 16 years old. Physical examination revealed only myotonia and could not find muscle atrophy or cataracta which were usually found in myotonic dystrophy. The quadriceps muscle biopsy revealed complete absence of type IIB muscle fiber. We diagnosed her Becker type congenital myotonia by the clinical course and family history and the histopathological findings of quadriceps muscle. Myalgia which she complained seemed to have some connection with this disease. But we could not prove the pathogenesis of this myalgia. PMID- 2598541 TI - [A case of micrographia with the right hand due to left putaminal infarction]. AB - Micrographia due to focal cerebral disorder is very rare. We described a patient with micrographia due to a left putaminal infarction. Following an infarction involving the left putamen and corona radiata, a 58-year-old right-handed man developed micrographia with the right hand, right facial palsy, right hand clumsiness and slight aphasia. Micrographia finally disappeared by the seventh month. No parkinsonian features were noted. Our case suggests that micrographia is a disorder of the motor control system of handwriting which exists in the contralateral putamen, and has no relation with extrapyramidal signs like rigidity, tremor or akinesia. PMID- 2598542 TI - [Two cases of facial diplegia with elevated serum antibodies to Borrelia burgdorferi]. AB - Lyme disease, a tick-borne infection with spirochete named Borrelia burgdorferi, is a complex multi-organ disorder involving neurological complication. Recently, the existence of Lyme disease was also recognized in middle Japan. We described here two cases of facial diplegia with elevated serum antibodies to B. burgdorferi. Case 1 was a 48 year-old man, who developed facial diplegia on April 29, 1987, and referred to our hospital on May 1. Neurological examination showed facial diplegia in addition to right-sided hemiparesis due to head injury of twenty years ago. The cell count of the cerebrospinal fluid was 17/mm3 and the protein was 139.9 mg/dl. The serological examinations for B. burgdorferi were performed by means of immunoperoxidase test. This patient had no serum IgG antibodies to B. burgdorferi on admission. However, twelve weeks later his serum showed significant elevation of IgG antibodies (titer: X400). Tests for syphilis and leptospira were negative. Based on these observation, we considered that facial diplegia of this patient was associated with the infection of B. burgdorferi. His facial diplegia remained unchanged with oral corticosteroid treatment. Case 2 was a 64 year-old man, who developed facial diplegia on May 31, 1987, and referred to our hospital on June 3. Neurological examinations were entirely negative except for facial diplegia. The findings of the cerebrospinal fluid showed the albumin cytologic dissociation with the cell count 2/mm3 and the protein 85.4 mg/dl. Serum IgG antibodies to B. burgdorferi were present (titer: X200) on admission. However, seven weeks later his serum showed a marked elevation of IgG antibodies (titer: X1600). Tests for syphilis were negative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598543 TI - [A case of ischemic disturbance of inner ear]. AB - We reported a 51-year-old male with ischemic disturbance of right inner ear resembling Meniere's disease. The patient had a sudden-onset episode of vertigo, right severe hearing disturbance, nausea, vomiting and gait disturbance. Two days after, he had hypersomnia, vertical gaze palsy, double vision, left Horner's sign, and sensory disturbance of pain and temperature of right half body involving face. Brain MRI disclosed high intensity area in T2-weighted image and proton density in bilateral paramedian thalamo-mesencephalic region and right cerebellum (area of the anterior inferior cerebellar artery). Cerebral angiography showed 90% or more stenosis of the right vertebral artery, 50% stenosis of the left vertebral artery before the posterior inferior cerebellar artery (PICA), and 60% stenosis of distal portion of the basilar artery. Furthermore, stem portion of the posterior cerebral artery, and the right anterior cerebellar artery and the left vertebral artery after the PICA were absent or occluded. Right deafness was evaluated to be Jerger type II, namely disturbance of inner ear. Caloric tests showed no response, and right auditory brainstem response showed no waves. Main cause of this vertigo and right deafness was considered to be disturbance of inner ear due to ischemia of right labyrinthine artery, though this patient was not a typical case of the anterior cerebellar artery syndrome. Ischemic disturbances of inner ear have been reported only in patients with the anterior cerebellar artery syndrome, therefore this patient who had only acute ischemic disturbance of inner ear and did not have disturbance of caudo-lateral portion of the pons was considered to be very rare. PMID- 2598544 TI - [An autopsy case of senile dementia with numerous neocortical senile plaques and preserved subcortical nuclei]. AB - An 80-year-old retired teacher developed impairment of memory and suffered from delusions of theft. Four years later, she became disoriented as to person, time and situation, restless, began mutter to herself, and displayed night delirium and insomnia. She was subsequently diagnosed as having senile dementia of the Alzheimer type (SDAT). She died of bronchopneumonia and multiple metastases from breast cancer at the age of 85 years. Family history was non-contributory. The brain weighed 1,020 g and showed diffuse atrophy. Histologically, there was moderate loss of neurons in the cerebral cortex, which was accentuated in the frontal and temporal lobes. In addition, numerous senile plaques were observed in the neocortex and hippocampus. Several senile plaques were also found in the amygdala, innominate substance, neostriatum, claustrum, thalamus, hypothalamus and tegmentum of the mesencephalon. Neurofibrillary tangles (NFTs) were mostly restricted to the hippocampus and parahippocampal gyrus, their number being compatible with the patient's age. No obvious neuronal loss was noted in the nucleus basalis of Meynert, neostriatum, substantia nigra or locus ceruleus, which are well known to be involved in Alzheimer's disease and SDAT. Recently, Terry et al proposed a new disease concept, "SDAT without neocortical NFTs". The histopathology of the cerebral cortex in our patient was very similar, if not identical, to those observed in their patients. However, the above authors did not mention any subcortical changes, leaving the detailed neuropathological picture unclear. Tentatively, we classified the present case as senile dementia with numerous neocortical senile plaques and preserved subcortical nuclei.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598545 TI - [A case of rhabdomyolysis following long time immobile posture caused by schizophrenia]. AB - A 39-year-old female with several past psychiatric hospitalization for schizophrenia was admitted to our hospital because of severe pain and swelling of her legs. A few days before onset, she had often sat down upon her heels in water closet, agitated and talking to herself for many hours. Two days before the admission, she had suffered from severe pain and swelling of her bilateral calf muscles, and her urine became brownish. On admission, neurological findings revealed delirious state, moderate rigidity of limbs, hyporeflexia of legs, marked swelling and severe spontaneous pain in bilateral legs. She was afebrile with body temperature of 36.4 degrees C. Laboratory data showed marked increase of levels of serum CK to 163,000 U/1, myoglobin to 9,860 ng/ml and aldolase to 42.8 IU/1, and the diagnosis of rhabdomyolysis was made. Although she fell into acute renal failure, the renal function recovered after repeated hemodialysis. Several days after admission, swelling and pain of calf-muscles began to improve, and serum CK, myoglobin and aldolase decreased rapidly. One month later, she was able to walk on her own legs. In the literature, rhabdomyolysis associated with immobile posture caused by schizophrenia is extremely rare, and this is the first case reported in Japan. The relationship between rhabdomyolysis and schizophrenia was discussed. PMID- 2598546 TI - [A case of amyotrophic lateral sclerosis associated with clinical features of progressive supranuclear palsy]. AB - A 64-year-old male patient of amyotrophic lateral sclerosis (ALS) with frozen gait, axial rigidity and supranuclear upper gaze palsy was reported. We have followed this patient more than four years. He was well until November 1982, when he noticed weakness of left arm. In March 1983, he noticed hypogeusia and in July, he developed dysarthria and frozen gait. On admission, he was alert and oriented. Neurological examination revealed dysarthria, dysphagia and muscular weakness and atrophy in bilateral upper extremities, dominantly in left side. He showed remarkable frozen gait, retropulsion and could not walk. Brain CT showed mild dilatation of the third ventricle. In August 1988, he showed tongue atrophy, and weakness and atrophy of the extremities progressed during these four years. He also showed axial rigidity and frozen gait. Brain CT showed severe third ventricular dilatation and atrophy of tegmentum of the midbrain and cerebellum that were compatible with progressive supranuclear palsy (PSP). Six months later, he developed upper gaze palsy. From these findings, we concluded that this patient had a quite unique clinical features of both ALS and PSP. PMID- 2598547 TI - [Chronic progressive external ophthalmoplegia (CPEO) with deleted mitochondrial DNA]. AB - A 19-year-old man with chronic progressive external ophthalmoplegia with deleted mitochondrial DNA was reported. Neurological examination revealed bilateral external ophthalmoplegia, hearing loss of sensorineural type, short stature, mental retardation, muscle atrophy and weakness in the proximal muscles. Lactate and pyruvate levels were elevated in both serum and cerebrospinal fluid (CSF). Protein concentration was slightly increased in CSF. Electromyogram showed myopathic changes on all the muscles examined. Ragged-red fibers were found in biopsied rectus femoris muscle, stained with modified Gomori trichrome. Scattered cytochrome c oxidase deficient fibers were encountered. The computed tomography of the brain showed mild cerebral and cerebellar atrophy without any abnormal calcification or hypo-lucency. Southern blot analysis of the mitochondrial DNA (mtDNA) extracted from the patient's muscle revealed mixed population of mtDNA, consisting of the normal one and partially deleted one. The size of the deletion was about 4.5-kilobase. The region included the sequences coding for at least four subunits of Complex I, one subunit of Complex IV, two subunits of Complex V and five tRNAs. There may be a "hot area" on the mitochondrial genome that is more prone to be deleted than other regions of mtDNA. Southern blot analysis is usefull for the diagnosis of KSS or CPEO. PMID- 2598550 TI - Liver cysts associated with polycystic kidney disease: role of Tc-99m hepatobiliary imaging. AB - A 42-year-old woman with multiple hepatic cysts associated with autosomal polycystic kidney disease was evaluated for abdominal discomfort and new liver test abnormalities following blind aspirations of her liver cysts. Tc-99m mebrofenin hepatobiliary imaging revealed a markedly enlarged liver with multiple photon deficient areas, focal retention of isotope in the left hepatic ductal system, no accumulation of radionuclide in cysts, and an unusual medial gallbladder position. Endoscopic retrograde cholangiography confirmed all of these findings. Abdominal discomfort and liver biochemical abnormalities were attributed to cyst compression of nearby structures, including bile ducts. Hepatobiliary imaging is useful to exclude communication of bile ducts with hepatic cysts, to detect incidental abnormalities such as partial bile duct obstruction, and to distinguish the gallbladder from nearby hepatic cysts. PMID- 2598548 TI - [Recurrent episodic unilateral mydriasis with pleocytosis in the cerebrospinal fluid--a case report]. AB - A 24-year-old female was admitted to our hospital on Aug. 20 in 1986 because of blurred vision and right pupillary dilatation. She had sometimes noticed headache later than 1976, and blurred vision without headache several times a year later than 1983. She had been told her right pupil dilated when she had complained of blurred vision. Neurological examination revealed abnormal findings as follows; diminished sense of smell in the right side, anisocoria (R 8 mm, L 5 mm), bilateral hippus, hypesthesioalgesia in her right face, left trunk and left arm. The pupils were round and contracted promptly to light. Accommodation reflex and ciliospinal reflexes were normal. Neither blepharoptosis nor external ocular muscle paresis were observed. Deep tendon reflexes were normal. Planter responses were flexor. There was no meningeal irritative sign. No abnormal findings were obtained in blood and urine, chest X-p, brain enhanced CT scan, EEG, and cerebral angiography except for slight degree of anemia. Serum TPHA was negative. However, the cell count of cerebrospinal fluid (CSF) was 18/mm3 (Ly 100%) and decreased to 9/mm3 (Ly 100%) in nine days. Protein content and glucose level of CSF were normal. Pupils were not constricted by 0.125% pilocarpine instillation. Loss of smell and sensory disturbance disappeared within three days and her pupils became isocoric by five days after admission. The patients of episodic unilateral mydriasis without apparent cause had relatively same clinical features as "unilateral springing pupil" proposed by Hallett et al. (1970). Except for mydriasis, they had no abnormal findings of neurological and laboratory examinations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598551 TI - The use of SPECT in the diagnosis of epiphyseal osteoid osteoma. AB - An osteoid osteoma, which rarely occurs in an intraepiphyseal site, was identified by SPECT imaging in the proximal tibial epiphysis of a boy who had lower back pain, which had not been explained prior investigations. PMID- 2598549 TI - [Progressive hemifacial atrophy with sympathetic nerve dysfunction of central origin]. AB - A 37-year-old unmarried man was admitted because of gait disturbance and right hemifacial atrophy. Family history was unremarkable. He had an unconscious attack at age 13 and had writer's cramp since age 15. He was thin and lipodystrophic. In reviewing his portraits, hemifacial atrophy was considered to develop in his early teens and to be progressive since then. Pigmented gum, high arched palate, mild mental retardation, pseudo-Argyll Robertson's pupil, sexual impotence, amyotrophy of the left thigh and the right calf, and a limp due to bony abnormalities was detected. Serological tests for syphilis were negative. Bone X rays disclosed coxa-deformance. Cerebrospinal fluid. EMG, EEG, muscle biopsy and brain CT were normal. Hearing was decreased to 20-35 dB bilaterally. Plasma norepinephrine levels were 450 pg/ml in the supine position and 539 pg/ml in standing. Plasma renin activity was 5.1-5.4 ng/ml/hr. Microneurography revealed highly accentuated muscle and skin sympathetic nerve activities. Hypothermia on the feet, reduced CVR-R and decreased mydriatic response to 5% cocaine instillation were present. Intravenous infusion of norepinephrine and intradermal injection of either acetylcholine or histamine revealed normal results. In the case, sympathicotonia due to dysfunction in the central nervous system is considered to be related to the pathogenesis of hemifacial atrophy. PMID- 2598552 TI - Focal nodular hyperplasia of the liver: correlation of Tc-99m DISIDA "hot spot" appearance with histopathologic findings. AB - The scintigraphic appearance of hepatic focal nodular hyperplasia of "hot spot" seen on hepatobiliary scintigraphy is correlated with the histopathological appearance of bile ductular cell proliferation seen in this lesion. PMID- 2598553 TI - Utility of the SPECT Tc-99m labeled RBC blood pool scan in the detection of hepatic hemangiomas. AB - The sensitivity of SPECT imaging of hepatic blood pool activity using Tc-99m labeled RBCs was contrasted with magnetic resonance and CT imaging in 22 cases. SPECT is a noninvasive technique with a high sensitivity for the diagnosis of hepatic hemangiomas. It is helpful for clarifying equivocal magnetic resonance imaging results. PMID- 2598554 TI - False-negative radionuclide cisternography in massive communicating hydrocephalus: value of the vertex view and CT correlation. AB - Radionuclide cisternography evaluates cerebrospinal fluid dynamics, while CT and magnetic resonance imaging provide better information about central nervous system anatomy. This article describes two cases of patients with hydrocephalus. Their radionuclide cysternography studies were initially felt to be normal. After correlation with CT scans, massively enlarged ventricles were discovered. Tracer activity had refluxed into the ventricles, simulating normal cerebrospinal fluid rise over the convexities. When radionuclide cisternography studies in patients with excessively enlarged ventricles are interpreted, correlation with other anatomic imaging studies, such as CT and magnetic resonance imaging, is essential. A vertex view acquired during cisternography may also be helpful in correlation with transaxial plane images obtained by CT and magnetic resonance imaging. PMID- 2598555 TI - Gallium SPECT detection of neoplastic intravascular obstruction of the superior vena cava. AB - A rare case of an intravascular neoplastic obstruction of the superior vena cava is discussed. The lesion was detected with gallium single photon emission computed tomography (SPECT) despite a normal appearance on a concurrent radiographic CT study. A computer-generated composite SPECT-CT image confirmed the intravascular localization of the radioisotope, and a subsequent CT-guided transthoracic needle biopsy revealed a poorly differentiated adenocarcinoma. PMID- 2598556 TI - Tl-201 myocardial SPECT in patients with Duchenne's muscular dystrophy: a long term follow-up. AB - Tl-201 SPECT was used to evaluate myocardial involvement in 13 patients with Duchenne's muscular dystrophy. Serial studies of 9 patients were done at two-year intervals. The hypoperfused areas of the left ventricle became more prominent with age and severity. PMID- 2598557 TI - Patent ductus arteriosus with Eisenmenger's syndrome detected by first-pass study. AB - The case of a 20-year-old man with patent ductus arteriosus complicated with Eisenmenger's syndrome is described. Radionuclide angiocardiography characterized the abnormal pattern of blood flow through the central circulation to establish a diagnosis of patent ductus arteriosus with a significant right-to-left shunt, which had not been indicated by other clinical findings. PMID- 2598559 TI - Iodoamphetamine-123 brain imaging demonstrating cortical deactivation in a patient with progressive supranuclear palsy. PMID- 2598558 TI - Orbital pseudotumor imaged with Ga-67 citrate. AB - An orbital pseudotumor causing proptosis, diplopia, and gaze palsy was imaged with Ga-67 citrate and showed persistent intense activity for five days. This may be the first case of gallium uptake into an orbital pseudotumor to be reported in the literature. This case report demonstrates the use of Ga-67 citrate imaging in the early diagnostic workup of this disorder. PMID- 2598561 TI - Failure of exogenous TSH to stimulate suppressed tissue in a case of toxic adenoma. PMID- 2598560 TI - Avid accumulation of Ga-67 citrate in adenocarcinoma of pancreas. PMID- 2598562 TI - "Ink blot" bone imaging in metastatic osteogenic sarcoma. PMID- 2598565 TI - Effects of age on the elimination of labetalol. AB - Labetalol is an alpha 1- and beta-adrenergic antagonist currently used in the treatment of hypertension. Studies which have evaluated the effects of age on its pharmacokinetics have yielded conflicting results. The purpose of this study is to comprehensively re-evaluate the effect of age on the elimination of labetalol. Data were obtained from 4 single-dose and 3 multiple-dose studies of the pharmacokinetics of the drug. An analysis of covariance was performed on the single-dose data to determine whether the type of subject evaluated (normotensive vs hypertensive), type of assay methodology used and/or age were significant factors affecting labetalol clearance estimates. A similar covariance procedure was used for the multiple-dose data, to assess whether the type of subject, duration of treatment and/or age were significant variables affecting labetalol elimination. Subsequent to the analysis of covariance, linear regression and correlation analysis was used to evaluate the effects of age on labetalol clearance. A modest though significant relationship was observed between the apparent oral clearance of the drug and age; it appeared slightly stronger when clearance was normalised for bodyweight. No relationship was found following multiple doses of the drug. Hence, age does not appear to be a significant factor affecting the oral clearance of labetalol, particularly in individuals receiving the drug in the long term. PMID- 2598564 TI - Skeletal scintigraphy of multiple bone infarctions. PMID- 2598563 TI - Transient decrease in I-131 and Tc-99m thyroid uptake after neck trauma. PMID- 2598566 TI - Pharmacokinetics and pharmacodynamics of atenolol in children. AB - The pharmacokinetics and pharmacodynamics of intravenous atenolol were studied in 10 children during cardiac electrophysiologic studies. The intravenous pharmacokinetic data were best described by a two-compartment model and revealed the following (mean +/- SD): total body clearance, 0.15 +/- 0.06 L/hr/kg; volume of the central compartment 0.33 +/- 0.06 L/kg; volume of distribution at steady state, 0.83 +/- 0.15 L/kg; distributive elimination half-life, 0.29 +/- 0.08 hour; and terminal elimination half-life, 4.56 +/- 1.05 hours. The data suggest that children have a slightly shorter terminal elimination half-life than that of adults. Pharmacodynamic data showed a significantly (p less than 0.01) increased sinus cycle length and an increase in His to ventricle conduction time (p less than 0.05). Further studies are necessary to determine the optimal oral dose and dosing frequency of atenolol and to access the response of children to long-term treatment. PMID- 2598568 TI - Pharmacokinetics of nicotinic acid-salicylic acid interaction. AB - Both nicotinic acid and salicylic acid undergo glycine conjugation in human beings. Competitive inhibition may therefore be possible when these substances are used concomitantly in patients with hyperlipidemic disorders. The aim of this study was to determine, in six healthy subjects, whether nicotinic acid steady state levels and total clearance are affected by concomitant aspirin administration. Steady-state nicotinic acid concentrations were obtained in all six volunteers by infusion of nicotinic acid solutions at constant rates (0.075 to 0.100 mg/kg/min) for 6 hours; aspirin (1 gm) was administered orally 120 minutes after the beginning of the infusion of nicotinic acid. Plasma samples were analyzed for nicotinic acid, nicotinuric acid, and salicylic acid. After aspirin administration an immediate marked decrease of nicotinuric acid levels could be observed in all six volunteers, whereas nicotinic acid concentrations increased. We hypothesize that salicylic acid causes a concentration-dependent decrease of total nicotinic acid clearance that results in the saturation (and effective elimination) of the nicotinuric acid conjugation pathway. PMID- 2598567 TI - Pharmacokinetics of tacrine hydrochloride in Alzheimer's disease. AB - The clinical pharmacokinetics of tacrine hydrochloride have been characterized in patients who have Alzheimer's disease. Serum concentrations of the drug and of its probable metabolite were monitored in eight patients after a 25 mg oral dose, in six patients after a 50 mg oral dose, in four patients after repeated administration of 50 mg, and in two patients after a small intravenous dose. Urinary excretion of drug and metabolite for 24 hours was measured in one of the patients who received a small intravenous dose. The serum half-life was 1.59 +/- 0.15 hours (mean +/- SEM) after the 25 mg dose, 2.14 +/- 0.24 hours after the 50 mg dose, and 2.91 +/- 0.39 hours after continuous treatment. After intravenous administration, clearance was above 600 ml/min in both patients, and oral bioavailability was calculated at below 5%. Urine recovery was less than 3% of the dose. The low bioavailability of tacrine hydrochloride is partly explained by presystemic metabolism. PMID- 2598569 TI - Pharmacokinetics and pharmacodynamics of dilevalol. AB - The pharmacokinetics and pharmacodynamics of dilevalol, the R,R stereoisomer of labetalol, were evaluated in nine subjects. Dilevalol was given as a single 50 mg intravenous dose and as a 400 mg daily oral dose for 7 days. To study the effects of hepatic enzyme inhibition, each subject received dilevalol in the presence of and absence of cimetidine. Cardiac beta-blockade was assessed by use of standardized treadmill tests for 48 hours after oral dilevalol. The three compartment model analysis showed that systemic clearance (29.8 +/- 5.7 ml/min/kg), volume of distribution (16.6 +/- 4.1 L/kg), and terminal half-life (11.7 +/- 2.7 hours) were not altered by cimetidine. However, there was a 20% increase in the area under the curve (p less than 0.05) and an 11% increase in systemic bioavailability (p less than 0.05) after oral administration. Dilevalol caused significant cardiac beta-blockade for more than 24 hours, but these effects were not altered by cimetidine. The pharmacokinetic changes are consistent with a decrease in first-pass extraction of a high clearance drug. PMID- 2598570 TI - The epidemiology of the acute flank pain syndrome from suprofen. AB - Suprofen, a new nonsteroidal anti-inflammatory drug, was marketed in early 1986 as an analgesic agent. Until physicians began reporting an unusual acute flank pain syndrome to the spontaneous reporting system, 700,000 persons used the drug in the United States. Through August 1986, a total of 163 cases of this syndrome were reported. To elucidate the epidemiology of the syndrome, a case-control study was performed, comparing 62 of the case patients who had been reported to the spontaneous reporting system to 185 suprofen-exposed control subjects who did not have the syndrome. Case patients were more likely to be men (odds ratio, 3.8; 95% confidence interval, 1.2-12.1), suffer from hay fever and asthma (odds ratio, 3.4; 95% confidence interval, 1.0-11.9); to participate in regular exercise (odds ratio, 5.9; 95% confidence interval, 1.1-30.7), especially in the use of Nautilus equipment (p = 0.02); and to use alcohol (odds ratio, 4.4; 95% confidence interval, 1.1-17.5). Possible risk factors included young age, concurrent use of other analgesic agents (especially ibuprofen), preexisting renal disease, a history of kidney stones, a history of gout, a recent increase in activity, a recent increase in sun exposure, and residence in the Sunbelt. These were findings that were suggestive but did not reach conventional statistical significance. These findings are consistent with the postulated mechanism for this unusual syndrome: acute diffuse crystallization of uric acid in renal tubules. PMID- 2598572 TI - The effect of a Microsil-containing dentifrice in the prevention and treatment of gingivitis. AB - The purpose of this study was to determine if a Microsil-containing dentifrice (Minnetonka, Inc., Minnetonka, Minnesota) could enhance the therapeutic effectiveness of toothbrushing relative to plaque control as well as the prevention and treatment of gingivitis. Volunteer 12 through 14 year-old elementary school students were divided into two experimental groups and one control group. Following baseline examination, scorings were made after consecutive forty-five day experimental periods which were separated by an interim prophylaxis. One of the Microsil-containing dentifrices was found to significantly reduce existing plaque and gingivitis levels at specific locations. The same experimental dentifrice was also shown in specific areas to permit better maintenance of the reduced gingivitis levels achieved following prophylaxis. It was concluded that the results obtained with a Microsil containing dentifrice were encouraging in that any additional effect in reducing plaque and controlling gingivitis would be especially beneficial for young individuals in whom gingivitis is such a common finding. PMID- 2598571 TI - Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin. AB - The effect of an antacid (Maalox) and ranitidine administration on the absorption of ciprofloxacin was evaluated in healthy male volunteers who were enrolled in three separate studies. Each study was designed at a three- or four-period crossover and included the administration of 750 mg ciprofloxacin alone as a control treatment. Treatments that were evaluated included the administration of ciprofloxacin 5 to 10 minutes, 2 hours, 4 hours, and 6 hours after a single 30 ml dose of antacid; the administration of antacid 2 hours after ciprofloxacin was given; and the administration of ciprofloxacin 2 hours after a 200 mg ranitidine tablet. Administration of antacid within 4 hours before ciprofloxacin dose resulted in a significant decrease in ciprofloxacin absorption (p less than 0.05). Percentages of relative bioavailability compared with control values were 15.1%, 23.2%, and 70% for the 5 to 10 minute, 2 hour, and 4 hour antacid pretreatments, respectively. Administration of antacid 6 hours before or 2 hours after the ciprofloxacin dose did not affect absorption. Ranitidine did not alter ciprofloxacin absorption. Antacids that contain magnesium and aluminum salts may reduce the absorption of ciprofloxacin. The extent of this interaction appears to increase as the time between administration of the two drugs decreases. Ranitidine is suggested as an alternative to antacids for patients receiving treatment with ciprofloxacin. PMID- 2598573 TI - Radiography for the diagnosis of dental caries in posterior teeth. AB - The role of radiography in the detection and monitoring of dental caries in posterior teeth is reviewed. Variables in radiographic technique, including the use of different image projections and receptors, are considered. The contribution of radiography to the diagnosis of approximal, occlusal, and recurrent caries is reviewed, as is the use of radiography for the monitoring of caries progression. PMID- 2598574 TI - Cervical strain and mandibular whiplash: effects upon the craniomandibular apparatus. AB - One of the most common injuries that can lead to a multitude of problems is cervical strain and mandibular whiplash resulting from a motor vehicle accident. Many individuals do not fully recover from such injuries, develop additional areas of pain and dysfunction weeks or months after the accident, and/or sustain major trauma that may require surgical intervention. Other than fractures or dislocations of cervical vertebrae, which are usually easily discerned from radiological analysis, two prime factors frequently lead to a prolongation of pain, a long rehabilitation course, and the development of problems at adjacent structures such as the craniomandibular region. These two factors are: 1) the lack of early comprehensive evaluation and referral for definitive therapeutic intervention, and 2) a minimal awareness of the relationship of upper quarter structures to one another. The purpose of this paper is to foster within the reader an appreciation of the interrelationship of the cervical and craniomandibular architectures as well as the significance of proper evaluation and treatment of cervical strain and mandibular whiplash injuries. PMID- 2598575 TI - The effect of a high consumption of apples or grapes on dental caries and periodontal disease in humans. AB - The intent of this study was to determine the effect of a high consumption of either apples or grapes on the caries experience (DMFT), and periodontal health. Farm workers employed by apple-producing, grape-producing and grain (control) producing farms in low fluoride areas (F less than 0.10 ppm) were investigated. To avoid contamination, only these farms where either apples, grapes or grain were cultivated solely, were included in the study. The caries incidence was found to be the highest for the apple group (24.2), lower for the grape group (17.4), and the lowest for the control group (9.9). The caries incidence differed statistically significantly (P less than 0.01) among the three groups. A higher caries incidence was found in the group of older subjects (35+ years) than in the 15-34 year old group. In general, for both age groups the control group showed conspicuously the highest number of dentate sextants with advanced periodontitis. Significantly less (P less than 0.01) advanced periodontitis and pocket formation could be seen in the youngest age group (15-34 years) of all three test groups. Thus, to conclude, it was found that the consumption of a high amount of apples and to a lesser degree grapes contributed significantly to dental caries. However, the above fruits had a beneficial effect on the periodontal status. PMID- 2598576 TI - Sterilization of operative dentistry instruments: a United States dental school survey. AB - Questionnaires were mailed to 58 department chairpersons of Operative Dentistry inviting comments about their sterilization and asepsis procedures. Results indicate that dental schools are responding to infection-control procedures in a variety of ways. PMID- 2598577 TI - The effect of hydrogenated starch hydrolysates on plaque pH in vivo. AB - The purpose of this research was to study the effect of five test hydrogenated starch hydrolysates on plaque pH in vivo. The results were compared with those produced by positive and negative controls. The results indicated that three test materials, Lycasin (Roquette Corporation, Gurnee, IL), Crystalline maltitol, and Maltisorb (Roquette Corporation, Gurnee, IL), were statistically equivalent to the negative control, sorbitol, and therefore can be considered noncariogenic. PMID- 2598578 TI - An evaluation of the effectiveness and patient compliance with plaque control methods in the prevention of periodontal disease. AB - The study was designed to evaluate the effectiveness of plaque control recommendations 6 months following active treatment of moderately advanced periodontal disease in 100 patients. The compliance of the patients to the use of different numbers of plaque control aids was also assessed. Our observations suggest that oral hygiene standards deteriorate during periods of unsupervised maintenance, and this is unrelated to either the number of aids recommended or the number of treatment visits. The reasons for patients failing to comply with professional recommendations were determined. PMID- 2598579 TI - Management of the acute TMJ emergency. AB - The urgent or after hours phone call to the dentist's office usually indicates a dental, traumatic, infectious, or pain emergency relating to the teeth or adjacent supporting structures. One subject not discussed at length in the professional literature is the emergency patient with acute pain or dysfunction of the orofacial musculoskeletal system, primarily the muscles of mastication and the temporomandibular joint (TMJ). The practitioner should be able to rapidly and efficiently diagnose and manage these emergency patients, or make adequate referral as necessary. Essential features in the diagnosis involve distinguishing muscle problems from intracapsular disorders. Knowledge of general medical-dental differential diagnosis is essential to rule out those problems masquerading as muscle or TMJ disorders. Proper emergency management is directed at controlling the pain or hypomobility disorder and stabilizing the patient. Contrary to most other aspects of dental practice, rapid and complete elimination of symptomatology may not be possible at this visit. Subsequent management should further define the pathologic process and direct the patient to additional phases of care. This report suggests a series of diagnostic and therapeutic guidelines. PMID- 2598580 TI - A microprocessor temperature-controlled air delivery system for dentinal hypersensitivity testing. AB - A new microprocessor temperature controlled air delivery system for determining cold and warm temperature thresholds of dentinal hypersensitivity has been designed and built. The temperature range of the unit is -5 degrees to + 85 degrees C. Air is delivered from a typical dental unit air syringe nozzle at a relatively gentle flow rate of 0.2 cu ft/min at operator selected temperatures, with an accuracy of +/- 0.2 degrees C. Within seconds, 1 degree to 5 degrees temperature increments or decrements are accomplished. Larger, i.e., 20 degree increments or decrements, require approximately 15 seconds. The unit can operate from standard 110 V/60 Hz or 230 V/50 Hz outlets and requires a source of compressed air at 60 psig, equivalent to that provided by dental operatory-type air compressors. This report provides a description of the unit, its operation, and data from two clinical studies in which it was used successfully to determine temperature thresholds of dentinal hypersensitivity. PMID- 2598582 TI - Fetal echocardiography--four years experience in Bristol. AB - Fetal echocardiography is described as a reliable method for detecting major structural cardiac abnormalities but relatively few hospitals offer the investigation. We report the results of fetal echocardiography in 110 pregnancies referred to our cardiac ultrasound service. Standard imaging techniques were used and scanning was carried out at 18-24 weeks gestation in the majority. Most referrals were made with a history of congenital heart disease in a sibling or close relative, the remainder followed abnormal routine scans or for other reasons. Four structural cardiac abnormalities were diagnosed in the routine scan abnormality group and one in the positive family history group. Referring clinicians reported no subsequent cardiac abnormality following normal scans. We confirm that provided a careful and systematic technique is used fetal echocardiography is reliable in detecting major structural cardiac defects. Particular attention should be paid to the fetal heart in patients with previously abnormal routine scans as this group accounts for the majority of detected congenital cardiac anomalies. PMID- 2598581 TI - The value of computed tomography in the diagnosis of amiodarone-induced pulmonary toxicity. AB - Amiodarone hydrochloride (Cordarone) is an effective antiarrhythmic drug which can cause a potentially fatal pneumonitis. The clinical diagnosis is difficult and investigation non-specific. Narrow section computed tomography (CT) was performed in nine patients who developed new respiratory symptoms during treatment with amiodarone. All had chest radiographs prior to CT, six had respiratory function tests and four had serum amiodarone estimations. High density basal peripheral pleuro-parenchymal lesions were seen in four of the nine patients. These appearances were compatible with those previously detected in other pulmonary interstitial lung diseases. We suggest that CT is a useful investigation in patients with suspected amiodarone pulmonary toxicity. PMID- 2598583 TI - Radiological features of AIDS related cholangitis. AB - Cryptosporidial infection is one of the recognised causes of diarrhoea in AIDS patients. It may also produce biliary tract disease. Fifteen out of 250 (6%) AIDS patients seen at our hospital had Cryptosporidial enteritis and five of the 15 (2% total) had clinical evidence of biliary tract disease. The radiological findings in these five patients are presented. Ultrasound examination of all five patients showed abnormalities in the biliary tree; five had dilatation and irregularity of the intra- and extrahepatic bile ducts with focal strictures, four had gall-bladder wall thickening, two had thickening of the common bile duct wall, two patients showed areas of increased reflectivity in the periductal regions of the liver and two had pancreatic duct dilatation. ERCP in one patient confirmed the ultrasound findings and Cryptosporidium oocytes were isolated from the collected bile. We conclude that Cryptosporidial infection in the biliary tree can produce distinctive appearances on ultrasound which may well obviate the need for more invasive investigations such as ERCP. PMID- 2598584 TI - Non-operative management of gallstones--a preliminary review. AB - We describe our initial experience with extracorporeal shock-wave lithotripsy, direct solvent dissolution with methyl tert-butyl ether and mechanical extraction, in 17 symptomatic patients without significant gall-bladder wall disease using existing criteria for selection. Extracorporeal shock-wave lithotripsy and mechanical extraction are promising techniques. Methyl tert-butyl ether therapy has been fraught with difficulty. PMID- 2598585 TI - A comparative study to evaluate the role of intra-articular adrenaline in double contrast knee arthrography. AB - The addition of adrenaline to meglumine iothalamate (Conray 280) in double contrast knee arthrography significantly improves meniscal coating, in both immediate and delayed films, when compared with iothalamate alone. The quality of coating is comparable to that with sodium meglumine ioxaglate (Hexabrix 320) without adrenaline. The addition of adrenaline to ioxaglate produces no significant improvement in arthrographic quality in either immediate or delayed films. The use of iothalamate with adrenaline is less expensive than ioxaglate alone, but this financial advantage has to be balanced against the significantly greater pain associated with the use of intra-articular adrenaline. PMID- 2598586 TI - Psoas nodes--an overlooked site of metastasis from testicular tumours. AB - This paper describes six patients with testicular tumours in whom computed tomography (CT) scanning at presentation (one case) or relapse (five cases) showed metastases to sites on the psoas muscle at, or below, the level of the aortic bifurcation. Evidence for the existence of retroperitoneal lymph nodes low on the psoas muscles is presented and the importance of recognising this as a possible site of metastasis from testicular tumours is discussed. PMID- 2598588 TI - Reduction of ocular lens dosage in dacrocystography. AB - Irradiation of the lens of the eye in dacrocystography is largely avoidable. We have measured the lens dosage in bilateral dacrocystography in vivo and in a phantom. We describe simple protective measures which can reduce the lens dosage by over 95% to less than one mGy. PMID- 2598587 TI - Localisation of intraocular and intraorbital foreign bodies using computed tomography. AB - Accurate localisation of foreign bodies in the region of the orbit is vital for correct management. Fifteen patients with such foreign bodies are described. Computed tomography (CT) of the orbits proved accurate in differentiating extraocular and intraocular foreign bodies, and in localisation within the globe. If a foreign body is visible on a plain radiograph, axial 6 mm thick CT sections will demonstrate it in all cases. If plain radiographs are negative or equivocal, 3 mm thick CT sections are necessary. Coronal scans are of limited usefulness. PMID- 2598589 TI - The significance of haematomas of the basal ganglia in closed head injury. AB - In a large series of patients with severe closed head injury, 26 (3.2%) had haematomas of the basal ganglia. It is suggested that such haematomas indicate primary brain damage, being part of the spectrum of lesions that may be seen in diffuse axonal injury. Clinical outcome was found to depend on the pattern of brain damage, notably on the additional presence of contusions or of other computed tomographic (CT) evidence of diffuse axonal injury. PMID- 2598590 TI - Central giant cell granuloma of the jaws: a clinico-radiological study. AB - There is disagreement in the literature about the radiological appearance of the central giant cell granuloma (CGCG) of the jaws. A review of 26 cases of CGCG was undertaken with the aim of resolving this. CGCG were found over a wide age range but most occurred in the 2nd and 3rd decades. Females were more frequently affected. Radiologically CGCG were most commonly seen as round or ovoid, unilocular, well defined but non-corticated radiolucencies in the mandible anterior to the first permanent molars. Expansion, either bony or soft tissue alone, was common. Internal calcification was sometimes seen. Teeth in contact with CGCG may lose their lamina dura and become displaced but resorption was rare. PMID- 2598591 TI - Fibrin sealant as a plug for the post liver biopsy needle track. AB - Some patients are at particular risk of haemorrhage after liver biopsy. We describe the use of a two-component fibrin sealant (Tisseel, Immuno) for embolising the track left after biopsy with the 18 gauge 'Biopty' needle. In our series of five cases there have been no bleeding complications. We consider Tisseel much easier to apply than previously described embolisation materials. PMID- 2598592 TI - Serious adverse reaction to patent blue violet at lymphography. AB - Allergic reactions during lymphography are uncommon, usually minor and difficult to attribute to a single agent because of the common practice of mixing patent blue dye and local anaesthetic before injection. A case is presented where injection of patent blue dye alone was followed by generalised urticaria, swelling and constriction in the throat and difficulty breathing. PMID- 2598593 TI - Magnetic resonance imaging of spinal amyloid. AB - This report describes a patient with a history of breast carcinoma who presented with back pain and multiple collapsed vertebrae. Magnetic resonance imaging (MRI) demonstrated a diffuse bone marrow abnormality, more in keeping with an infiltrative process than with metastases. A bone biopsy confirmed the suspected diagnosis of vertebral involvement by amyloid. PMID- 2598594 TI - CT demonstration of pituitary stalk relapse in childhood acute lymphoblastic leukaemia. AB - Central nervous system relapse in childhood acute lymphoblastic leukaemia (ALL) occurs in 8% (all risks). Leptomeningeal infiltration is the usual form of relapse and pituitary stalk involvement is rarely found. We report the CT demonstration of pituitary stalk relapse with endocrine evidence of disruption of the hypothalamo-pituitary axis. PMID- 2598595 TI - Abstracts of paper presented at the Royal College of Radiologists annual scientific meeting. 19-22 September 1989, Liverpool. PMID- 2598598 TI - CT of lumbar lymph trunks. PMID- 2598596 TI - Traumatic bowing of the ulna in an adult. PMID- 2598597 TI - The unshadowing of mammography. PMID- 2598600 TI - Should radiologists perform gastrointestinal endoscopy? PMID- 2598599 TI - Magnetic resonance imaging of intracranial epidermoid tumours. PMID- 2598601 TI - Whats in a name? PMID- 2598602 TI - Solving the ethical dilemma. PMID- 2598603 TI - Should ethics be added to the core curriculum? PMID- 2598604 TI - Rationing would stretch health care for poor. Interview by Kevin Doll. PMID- 2598605 TI - Disposal of infectious waste. PMID- 2598606 TI - Premedication for amphotericin B-induced chills. PMID- 2598607 TI - Possible diclofenac-quinolone interaction. PMID- 2598608 TI - General recommendations on immunization. Immunization Practices Advisory Committee. AB - This revision of the "General Recommendations on Immunization" updates the 1982 statement. Changes or new sections include (1) listing of vaccines available in the United States by type and recommended routes, (2) updated schedules for immunizing infants and children, (3) clarification of the guidelines for spacing administration of immune globulin preparations and different vaccines, (4) an updated table of recommendations for routine immunization of children infected with human immunodeficiency virus, (5) listing of conditions that are often inappropriately considered contraindications to immunization, and (6) addition of information on the National Childhood Vaccine Injury Act of 1986 and the National Vaccine Injury Compensation Program. These recommendations are not comprehensive for each vaccine; Immunization Practices Advisory Committee (ACIP) recommendations on each vaccine should be consulted for more details. PMID- 2598609 TI - Current information on the use of immunobiologics: comments of the ASHP Commission on Therapeutics. PMID- 2598610 TI - Evaluation of a capillary whole-blood prothrombin time measurement system. PMID- 2598611 TI - Arm and ankle blood pressure response to treadmill exercise in normal people. AB - Nineteen healthy volunteers, 10 men and nine women (mean age 38 and 30 years), exercised on a treadmill. The systolic blood pressure (BP) was measured at the ankle and in the arm after submaximal (8 min with a final load of 2 W kg-1 body weight) and maximal exercise. The BP was measured for 10 min after exercise, or until the elimination of a negative pressure difference between ankle and arm. The pre-study resting systolic arm and ankle pressures were 122 +/- 11 and 144 +/ 13 mmHg. One minute after submaximal exercise, arm and ankle BP were 147 +/- 18 and 159 +/- 19 mmHg (ankle-arm pressure difference 12 +/- 13 mmHg); 1 min after maximal exercise the corresponding figures were 182 +/- 26 and 153 +/- 35 mmHg (ankle-arm pressure difference -29 +/- 33 mmHg). We conclude that maximal exercise, but not an appropriately chosen submaximal exercise level, causes a negative BP difference between ankle and arm in normal people. PMID- 2598613 TI - Blood volume after coronary artery bypass grafting. AB - Patients with stable angina pectoris are reported to have a markedly reduced blood volume (BV). In the present study, average BV was still 19% less than that predicted in 77 men examined 5 years after coronary artery bypass grafting. Beneficial effects of the operation such as relieved angina, absence of medication, complete revascularization status at repeat angiography, and restored physical fitness were not found to be associated with a normalization of the BV. No significant correlation was found between BV and body weight, heart volume, exercise capacity, ejection fraction or left ventricular end-diastolic pressure. The reduced BV in patients with angina pectoris after successful revascularization and the absence of correlation with physiological variables indicate a persisting disturbed regulation mechanism. PMID- 2598612 TI - Role of leg vasculature in the cardiovascular response to arm work in wheelchair dependent populations. AB - To assess the effects of leg vasculature on cardiovascular dynamics during submaximal arm work, oxygen uptake (VO2), cardiac output (Q) and heart rate (HR) were measured during arm-crank ergometry (ACE) at 35 W (45% peak ACE VO2) in five able-bodied subjects, five wheelchair-dependent paraplegics, and five wheelchair dependent bilateral amputees who represented the conditions of active, passive, and absence of leg musculature respectively. Arteriovenous oxygen difference (a-v O2) and stroke volume (SV) were calculated from VO2, Q and HR. An index of leg fluid accumulation and leg blood flow was measured in the paraplegics and able bodied subjects during rest and ACE. VO2, Q, and a-v O2 during ACE were not statistically different among the three groups. However, paraplegics exhibited higher HR (P less than 0.05) and lower SV (P less than 0.06) during exercise compared to both amputees and able-bodied subjects. Greater (P less than 0.05) leg fluid accumulation was measured in paraplegics compared to able-bodied subjects, although no statistically significant differences in leg blood flow were observed. Although our results are limited to a small number of subjects, these data suggest that an active muscle pump contributes significantly to elevated venous return and stroke volume during ACE. The legs of the paraplegic appear to act as a reservoir for fluid accumulation which may limit cardiac filling, particularly during moderate arm work to support wheelchair function. PMID- 2598615 TI - Intrathoracic microvascular circulation in haemorrhagically shocked rats. Studies by fluorescence techniques. AB - The microvascular circulation in the heart, lung and thymus was studied by fluorometry in 32 haemorrhagically shocked rats. Exsanguination to a blood pressure of 35 mmHg for 180 min did not result in any reduction of this circulation in the heart or lung, but in the thymus it was reduced by 52%. Retransfusion of shed blood caused no change in cardiac microcirculation, whereas the microcirculation in the thymus was increased by 59%. In the lungs a heterogeneous fluorescence pattern was observed after retransfusion, with large dark areas alternating with normal fluorescent ones and even some small intensively fluorescent areas. After retransfusion, maldistribution of blood flow seems to be a phenomenon of haemorrhagic shock in the lungs. PMID- 2598614 TI - Exercise thallium-201 scintigraphy in the localization of myocardial ischaemia. AB - We performed a retrospective study in order to study the ability of thallium-201 exercise scintigraphy to detect and to localize coronary artery perfusion defects (in comparison with a recent coronary angiogram). We studied 81 patients (67 males); their average age was 52.3 years (men 50.5 and women 54.1 years). They performed a pulse-conducted cycle exercise test, and 2 min before end of exercise 75 MBq of thallium-201 was infused intravenously, and tomographic images were reconstructed by using a Siemens-Rota SPECT gamma camera immediately and 4 h after exercise. The thallium-201 uptake defects were attributed to different coronary arteries, and the results were compared with a coronary angiogram made afterwards in 48 patients. The groups of one-, two- and three-vessel disease were 27, 21, and 21 patients, and only 12 patients did not have significant (over 50%) stenoses. The latter had the highest ejection fraction and working capacity. Sensitivity of thallium-201 exercise scintigraphy was 65%, whereas that of exercise ECG was 41% in patients with a low ejection fraction, while in the whole material the sensitivity of thallium-201 scintigraphy was 91% and that of exercise ECG was 54%. A stenosis in the right coronary artery was best localized by the thallium-201 scintigram (86% correctly); a stenosis in the left anterior descending artery was localized correctly in 75% of the cases, but a stenosis in left circumflex artery was localized correctly only in 44%. We conclude that exercise thallium-201 scintigraphy is a useful method not only in detecting but also in localizing coronary artery disease. PMID- 2598617 TI - Pulmonary manifestations of systemic disease. PMID- 2598616 TI - Measurement of carboxyhaemoglobin by spectrophotometry and gas chromatography. AB - The purpose of this study was to evaluate state-of-the-art spectrophotometry for measurement of carboxyhaemoglobin (COHb). We measured the fractional concentration of COHb in 109 blood samples from patients under investigation of anaemia or with exposure to carbon monoxide (smokers) with the OSM3 Hemoximeter and by gas chromatography. Duplicate measurements were made with both methods in 42 samples. We found only a trivial systematic difference between the two methods. There was, however, a considerable scatter of the measurements, the limits of agreement (95% confidence limits for the difference between the two methods) being -0.98 and 0.86% COHb. The poor agreement between the methods was largely explained by a large random scatter in duplicate spectrophotometric measurements, whereas the method based on gas chromatography was highly reproducible. We conclude that the low accuracy of spectrophotometric measurements of COHb precludes its use for assessment of the endogenous production of CO, but that it may be useful for assessment of exposure to exogenous CO. PMID- 2598618 TI - Cross-cultural patterns in the training of children: an evolutionary perspective. AB - Analyzed cross-cultural child inculcation data from Barry, Josephson, Lauer, & Marshall (1976) by testing a hypothesis derived from natural selection theory: The ways in which boys are trained (vs. those for girls) should correlate with male and female reproductive strategies prevalent in each society. Boys are trained to be more aggressive, show more fortitude, and be more self-reliant than girls; girls are trained to be more industrious, responsible, obedient, and sexually restrained than boys. The more polygynous the society (the higher the potential reproductive rewards for males), the more sons in nonstratified societies were taught to strive. Stratified societies, which restrict men's reproductive striving, showed very different patterns. The more actual control women in any society had over resources, the less daughters were taught to be obedient. PMID- 2598619 TI - Central-place foraging by Rattus norvegicus on a radial maze. AB - We studied central-place foraging in rats (Rattus norvegicus) by placing food items that varied in size and weight at the ends of a 4-arm radial maze. In Experiments 1-3, rats increasingly tended to carry food to the center of the maze as the size of those items increased. Very large food items often were hoarded in the center. Rats consumed food faster on the arms than in the center, and rats traveled faster when carrying food than when not. Blocking arm entrances increased travel time between the center and the arms and decreased food carrying at every item weight except the largest. In Experiments 4-6, important conditions that influence the degree of food-carrying behavior were discovered; these were the intersection of maze arms, the presence of a conspecific, and the use of open vs. closed maze arms. PMID- 2598620 TI - Prior exposure to stress reduces the diversity of exploratory behavior of novel objects in the rat (Rattus norvegicus). AB - Although a large literature has documented the varied effects of stress on an organism, relatively little attention has been devoted to investigating stress effects in ecologically relevant situations. Our experiment was conducted to assess the effects of stress on rats' (Rattus norvegicus) exploration of novel objects in a seminaturalistic and familiar environment that is relatively free of the constraints that have been placed on rats in prior investigations of stress. The results show that prior exposure to stress decreased the rats' diversity of exploration but did not affect general activity in comparison with animals not exposed to stress. We propose that the effect of stress on the qualitative aspects of exploratory behavior may be due to effects on organisms' sensitivity to predation. PMID- 2598621 TI - Sexual-discrimination learning in male Japanese quail (Coturnix coturnix japonica). AB - We investigated how male Japanese quail (Coturnix coturnix japonica) learn through extensive social and sexual experience to discriminate between male and female conspecifics. Opportunity for heterosexual copulation was important for this learning, but even extensive copulatory opportunity was not sufficient to produce a sexual discrimination; subjects also required exposure to other males. Exposure to females after copulatory opportunity did not produce a sexual discrimination but facilitated its acquisition. Time or exposure to only the visual features of male birds (provided by taxidermic models) after copulatory opportunity did not result in differential responding to male and female conspecifics. Finally, presenting stimulus birds one at a time proved to be a more sensitive test of sexual-discrimination learning than presenting two stimulus birds at the same time. The results indicate that sexual-discrimination learning is similar to conventional associative learning. PMID- 2598622 TI - Development of defensive burying in Rattus norvegicus: experience and defensive responses. AB - Rats (Rattus norvegicus) deprived of the opportunity to interact with particulate matter until they were young adults engaged in defensive burying after they were shocked by a wire-wrapped dowel in a test chamber that held bedding material. Interacting with a particulate substrate during development is not necessary for the expression of defensive burying in adulthood. However, interacting with a particulate substrate early in the rats' lives did have a substantial effect on the emergence and maintenance of burying behavior. Defensive burying developed at a later age and declined at an earlier age in rats maintained on wire mesh from birth until testing than it did in rats raised until weaning on bedding and housed on mesh thereafter. Because defensive burying is a complex, flexible, yet reliable response sequence that cannot be performed without the appropriate substrate, it has considerable potential as a model for the study of the development of species-specific defense responses. PMID- 2598623 TI - Timbre control in zebra finch (Taeniopygia guttata) song syllables. AB - Zebra finch (Taeniopygia guttata) song syllables often include harmonically related frequency components. These harmonics may be suppressed, and this differential emphasis varies between the syllables in a song and between individual birds' songs. These patterns of harmonic suppression are timbre. Individual syllables' patterns of harmonic suppression are constant with adult males' songs. Young males that imitate the songs of older males also imitate their patterns of harmonic suppression. Syringeal denervation distorts these patterns, which suggests that they are produced through active control of the vocal organ. The selective suppression and emphasis of some harmonics creates a great number of possible timbre variants for any one syllable. These add signal diversity to the limited array of frequency modulations and range of fundamental frequencies found in zebra finch song. Analyses of bird song that disregard timbre may overlook a feature that is important in vocal communication. PMID- 2598624 TI - Partial mediation of strange-male-induced pregnancy blocks by sexual activity in mice (Mus musculus). AB - Novel male house mice (Mus musculus) can disrupt early pregnancy in females. Previous research focused on pheromonal rather than behavioral mediation of this phenomenon. In Experiment 1, novel males were housed with females shortly after insemination. Litter production was negatively correlated with the males' sexual activity. Experiment 2 replicated this finding with a larger sample. In Experiment 3, females were exposed to castrated males. Testosterone-treated males completely blocked pregnancy, whereas untreated males did not. In Experiment 4, castrated testosterone-treated males were presented at intervals after insemination. Pregnancy was totally blocked at Days 3 and 4 and mostly blocked at Days 1 and 2 but was less affected at Days 5 and 6. In Experiment 5, females were exposed through a wire-mesh grid to castrated males. Pregnancies occurred in all conditions, even with testosterone-treated males. These data suggest a role for sexual activity in male-induced pregnancy blocks. PMID- 2598625 TI - A comparative study of animal erythrocyte agglutinins from marine algae. AB - 1. Fifteen marine algal species were analyzed for agglutinins to rabbit, sheep and human A, B and O blood group erythrocytes. 2. Protein extracts from all marine algae agglutinated rabbit erythrocytes, whereas twelve and five extracts agglutinated sheep and human erythrocytes, respectively. 3. The highest agglutination titers were consistently observed with rabbit erythrocytes. 4. Dictyota dichotoma strongly agglutinated human B blood group erythrocytes relative to A and O group erythrocytes. 5. Agglutination titer of rabbit erythrocytes by six algal extracts was not inhibited by mono- or polysaccharides, yet was reduced by glycoproteins. PMID- 2598626 TI - The thermal properties of intestinal alkaline phosphatase of three kinds of deep water fish. AB - 1. The thermal properties of intestinal alkaline phosphatase were investigated with three species of deep-water fish in the temperature range of 0-70 C. 2. A relationship was found between the thermal stability of the enzyme and the fish origin. 3. Maximum activity of alkaline phosphatase of the fish that originated in tropical water, namely, Aphanopus carbo and Epigonus telescopus was 60 C, whereas the respective maximum enzyme activity of Etmopterus princeps that originated in the burial zone was 30 C. 4. A breakpoint at 10 degrees C in the Arrhenius plot of emzyme activity in the case of A. carbo and a lack of a break point in the case of E. telescopus and E. princeps, are in accordance with the stenothermic nature of the former and the everythermic nature of the two latter fish species. PMID- 2598627 TI - Arctic life adaptation--I. The function of reindeer hemoglobin. AB - 1. The functional properties of hemoglobin from the reindeer (Rangifer tarandus tarandus L.) are characterized as a function of pH, temperature and organic phosphate concentration. 2. Alongside overall similarities shared with most vertebrate hemoglobins, hemoglobin from the reindeer shows significant differences with respect to the effect of both organic phosphates and chloride anions. 3. The limited effect of temperature on oxygen binding (delta H = -4 kcal/mol O2) could be regarded as an interesting case of molecular adaptation to extreme environmental conditions. PMID- 2598628 TI - Lipoprotein lipase in rat heart--I. Characterization of tri-, di- and monoacylglycerol lipase activities in post-heparin effluents. AB - 1. The lipolytic activities that sequentially hydrolyze tri-, di- and monoacylglycerol in rat post-heparin heart effluents were examined. 2. Properties of triacylglycerol lipase (TAGL) activity were typical of lipoprotein lipase. Diacylglycerol lipase (DAGL) behaved similarly to TAGL, suggesting that both activities refer to the same catalytic entity. 3. Differences, particularly in thermal stability, between TAGL and DAGL activities on one hand, and monoacylglycerol lipase (MAGL) activity on the other, may reflect different intrinsic molecular properties. 4. TAGL, DAGL and MAGL activities could not be separated by physical means and appeared to belong to a single unit at the same site on the capillary wall. PMID- 2598629 TI - Arctic life adaptation--II. The function of musk ox (Ovibos muschatos) hemoglobin. AB - 1. The hemoglobin system from musk ox (Ovibos muschatos) has been characterized from the functional point of view with special regard to the effect of organic phosphates and temperature. 2. The results are similar to those previously obtained in the case of reindeer and confirm that hemoglobins from arctic animals may display very low enthalpy change for the reaction with oxygen. 3. This finding is considered an example of molecular adaptation of respiratory pigments to extreme environmental conditions. PMID- 2598630 TI - Arctic life adaptation--III. The function of whale (Balaenoptera acutorostrata) hemoglobin. AB - 1. The oxygen binding properties of the hemoglobin from the Lesser Rorqual, Balaenoptera acutorostrata, has been investigated with respect to the possible effects of organic phosphates on gas transport in arctic environments. 2. The intrinsic oxygen affinity of the hemoglobin is high and strongly modulated by the effects of organic phosphates. 3. In the absence of organic phosphates, the temperature sensitivity of oxygen binding expressed by the heat of oxygenation, delta H, is -16.2 kcal/mol when corrected for the heat of oxygen in solution. 4. In the presence of organic phosphates there is a marked decrease in the temperature sensitivity delta H approximately -5 kcal/mol). 5. This feature is of great importance for oxygen unloading in the flippers and the tail, where the temperature is lower than the trunk of the whale. 6. Furthermore the organic phosphates strongly increase the Bohr coefficient, delta log P50/delta pH, from less than -0.3 in stripped hemoglobin to about -1.5 when the hemoglobin is saturated with P6-inositol. 7. This feature may be of great physiological importance by reducing the CO2 tension and acidosis after a prolonged dive. PMID- 2598631 TI - Na+-independent and nonstereospecific transport of 2-hydroxy 4-methylthiobutanoic acid by brush border membrane vesicles from chick small intestine. AB - 1. The transport of L- and DL-2-hydroxy 4-methylthiobutanoic acid (HMB), the methionine hydroxy analogue, by brush border membrane vesicles (BBMV) from chick small intestine was the sum of a saturable Michaelian component and a diffusive term. 2. Unlike that of L- and DL-MET, uptake was Na+-independent and electroneutral. 3. The inhibition of L-HMB transport by L-lactate, a structural analogue, and D-HMB as well, was of the competitive type. 4. Preloading of BBMV with D-HMB but not with L-lactate or L-MET trans-stimulated the influx of labelled L-HMB. 5. HMB uptake by rat and chick intestinal BBMV exhibited similar characteristics but the chick nonstereospecific transport system appeared to be unable to carry out L-lactate translocation. PMID- 2598632 TI - Primary structures of dog and cat amyloid A proteins: comparison to human AA. AB - 1. The complete amino acid sequences of canine and feline amyloid A (AA) proteins were determined and compared with the sequence of human AA protein. 2. The dog and cat AA proteins were 84% homologous with human AA through residue 69. 3. Between the residues which correspond to 69 and 70 in the human sequence, the dog and cat proteins had an insertion of eight amino acids after which homology with human AA resumed. 4. While human AA commonly ends at position 76, the carboxyl termini of dog and cat AA proteins corresponded to position 86 in the sequence of the precursor protein-serum amyloid A. 5. These results are particularly interesting with respect to evolution of the serum amyloid A gene family. PMID- 2598633 TI - Lipoprotein lipase in rat heart--II. Influence of apolipoproteins and nutritional factors on tri-, di- and monoacylglycerol lipase activities in post-heparin effluents. AB - 1. The in vitro effects of serum and apolipoproteins (apo), and the influence of the nutritional state of the animals were compared on triacylglycerol lipase (TAGL), diacylglycerol lipase (DAGL) and monoacylglycerol lipase (MAGL) activities in post-heparin effluent from rat heart. 2. Serum and apoC-II stimulated DAGL and MAGL 3-fold less than TAGL, the activity that measures lipoprotein lipase (LPL). 3. The preexisting nutritional state of the heart, that strongly modulated LPL, did not influence DAGL and MAGL. 4. ApoA-I, apoC-I, apoC III1 and apoC-III2 did not stimulate LPL and counteracted its stimulation by apoC II; MAGL, and not DAGL, was inhibited by apoA-I and apoC-I, an effect reversed by apoC-II. 5. TAGL, DAGL and MAGL appeared to act as a single physiological unit, although differing in functional details; MAGL displayed the greatest dissimilarity. PMID- 2598635 TI - Development of an avian calcitonin radioimmunoassay using synthetic chicken calcitonin as immunogen. AB - 1. A sequential double antibody radioimmunoassay (RIA) has been developed using synthetic chicken calcitonin (CT) as antigen, tracer and standard. 2. The immunoassay has a minimum detection limit of 0.5 ng and effective dose (ED50) of 7 ng. Serial dilutions of chicken and turkey plasma were parallel to serial dilutions of CT standard. Extracts of chicken and turkey ultimobranchial glands caused parallel displacement of tracer similar to synthetic CT. 3. Primary antisera (anti-chicken CT) was raised in guinea pigs immunized with RIBI: animals treated with Freund's complete adjuvant failed to respond. 4. Chicken CT was determined to have a half-life of 60 sec in the turkey hen. Development of a homologous RIA for avian CT will allow studies to elucidate the role of this hormone in birds. PMID- 2598634 TI - Lipoprotein lipase in rat heart--III. Effects of sex steroid hormones on tri-, di and monoacylglycerol lipase activities in post-heparin effluents. AB - The in vivo administration of ethinylestradiol to female rats causes dose dependent decreases in tri-, di- and monoacylglycerol lipase activities in post heparin heart effluents; monoacylglycerol lipase is less sensitive to estrogen than the other two. PMID- 2598637 TI - Water buffalo (Bubalus bubalis) hemoglobins: an electrophoretic and chromatographic study. AB - 1. Hemoglobins from three phenotypes of Italian water buffalo (Bubalus bubalis), named AA, AB and BB, were selected by starch gel electrophoresis at alkaline pH and analyzed using polyacrylamide gel isoelectric focusing and subsequent analysis of titration curves to reveal differences between two types of hemoglobin identified as Hb fast and Hb slow. 2. Globins from Hb fast and Hb slow were purified by fast protein liquid chromatography (FPLC). Electrophoretic differences were found in the respective alpha-chains using polyacrylamide gel disc-electrophoresis at acid pH, polyacrylamide gel isoelectric focusing and by subsequently analyzing titration curves. 3. The results suggest that the alpha chains of Hb fast and Hb slow, called I alpha and II alpha, respectively, differ in at least two aminoacid residues. Subsequently, these amino acids were identified as lysine and cysteine. PMID- 2598636 TI - Effect of some metal ions on blood and liver delta-aminolevulinate dehydratase of Pimelodus maculatus (Pisces, Pimelodidae). AB - 1. delta-ALA-D from Pimelodus maculatus was inhibited in vitro by Cd2+ greater than Pb2+ greater than Hg2+ greater than Cu2+ greater than Zn2+ in blood and by Pb2+ greater than Cd2+ greater than Hg2+ greater than Cu2+ = Zn2+ in the liver. 2. Kinetic analysis of the inhibition by the metal ions showed that Cd2+ and Hg2+ act as non-competitive inhibitors on both sources. 3. Pb2+ showed a mixed type of inhibition in blood and a non-competitive type in the liver. 4. Zn2+ acted as a competitive or mixed inhibitor, on both sources, depending on concentration. PMID- 2598638 TI - Dissociation of the bovine serum retinol-binding protein-transthyretin complex and purification of the two interacting proteins. AB - 1. Retinol-binding protein is present in bovine serum essentially in the complexed form, bound to transthyretin, as in the case of the other mammalian retinol-binding proteins. 2. Bovine retinol-binding protein-transthyretin complex has the distinctive property of undergoing dissociation in the course of the DEAE Sephadex chromatography of serum proteins. Therefore, the isolation of uncomplexed retinol-binding protein upon chromatography on this resin cannot represent evidence for lack of binding between it and TTR in bovine plasma, in contrast with previously reported conclusions (Heller J. (1975) J. biol. Chem. 250, (6549-6554). 3. Purified bovine retinol-binding protein and transthyretin can reconstitute a tight complex. PMID- 2598640 TI - An expert system for early detection of cancer of the breast. AB - In order to study the relevancy of exploring complex expert systems for use by the lay public, an expert system for the early detection of cancer of the breast has been developed. The system consists of a conversion between a microcomputer and a woman who is anxious about breast cancer. The conversation is divided into two parts: one is listening to the woman's symptoms regarding the breast then giving advice, the other is an explanation of breast cancer and how to detect it in its early stages. After listening to the woman's symptoms, the computer presents its conclusion and suggests courses of action the woman should take. The system is written in Prolog. It was tried by women in a small town at a festival for health, by female patients who visit our hospital, and received a positive reaction. PMID- 2598639 TI - Characterization of cytochrome P-450-dependent activities in hagfish, dogfish, perch and spectacle caiman. AB - 1. Owing to interest in the original function and evolution of cytochrome P-450 this enzyme system was studied in four species each at different levels on the phylogenetic tree, representing Agnatha, Selachi, Teleostei, and Reptilia. 2. All species contained considerable amounts of hepatic microsomal cytochrome P-450. The content in dogfish, perch and spectacle caiman was 0.2-0.3 while in the dogfish it was 0.6 nmol per mg protein. 3. Hepatic microsomal cytochrome P-450 dependent ethylmorphine demethylase, benzo(a)pyrene hydroxylase, 7-ethoxycoumarin O-deethylase and 7-ethoxyresorufin-O-deethylase activities have been measured and the assays were carefully characterized with respect to pH-, protein content-, incubation time- and temperature-activity relationships. 4. The study revealed species-dependent differences in the liver microsomal cytochrome P-450 enzyme system, which could be due to differences in cytochrome P-450 composition or in the microenvironment around the enzyme. PMID- 2598641 TI - Determination of functional aerobic capacity using the microcomputer. AB - The general interest in the application of exercise testing to evaluate the work capacity or change in the functional ability of individuals has resulted in the development of a variety of non-invasive tests and test protocols such as the Bruce Treadmill Protocol. This paper presents a computer program written in BASIC that determines an individuals functional work capacity and functional age from minutes completed during a Bruce Treadmill incremental exercise test. Results are summarized in tabular as well as graphical format. The use of the Bruce Treadmill protocol in conjunction with this computer program provides another means of efficiently determining the exercise capability and functional status of a patient. PMID- 2598642 TI - A SAS program for evaluating person-years of risk in cohort studies. AB - A SAS macro, written to evaluate person-years of exposure in longitudinal studies, is presented in this paper. The program has the advantage of stratification by age groups and chronological subperiods, a feature recommended in long-term studies, involving temporal changes in patterns of outcome. The program creates a data set that can be utilized to calculate age-adjusted incidence rates in categories of risk factors for morbidity and mortality. PMID- 2598643 TI - TRACK: a FORTRAN program for calculating the Foulkes-Davis tracking index. AB - This paper describes a program that calculates the Foulkes-Davis tracking index, the probability that two individuals selected at random will have measurement curves that do not cross. PMID- 2598644 TI - Tissue distribution of radiolabelled human factor D in the male Sprague-Dawley rat. AB - Human factor D was purified, labelled with 125I and injected intracardially or intraperitoneally into male Sprague-Dawley rats. After intracardial administration, 80% of the radioactivity seen initially in the blood was eliminated within 5 min. The highest levels of radioactivity were recovered in the kidney cortex in both cases: maximally 24% of the total dose applied was recovered in this tissue 7 min after intracardial injection and 8-9% of the total dose 80-90 min after intraperitoneal administration. Significant amounts of radioactivity were also observed in the spleen, lungs, liver and heart muscle, but uptake by other tissues was very low. These results indicated that injected human factor D disappeared rapidly from the plasma of rats and uptake by the kidney cortex was one of the main routes of elimination. PMID- 2598646 TI - Reduced immune adherence of antigen/antibody complexes formed in the presence of complement in vivo and in vitro. AB - The adherence of complement-reacted immune complexes (ICs) to cells bearing C3b receptors depends on the characteristics of the IC used. The immune adherence of preformed ICs exposed in vitro or in vivo to complement has been well established, and was confirmed using different types of ICs-antigens used: BSA; BSA dimers and trimers; tetanus toxoid, and hepatitis B surface antigen. In contrast the same ICs did not bind to human red blood cells when formed in the presence of serum in vitro. ICs remained negative for immune adherence as well, when formed directly in vivo by the sequential injection of antibody and antigen in guinea pigs. These results suggest that in many circumstances, the elimination of ICs formed in the circulation does not involve immune adherence reactions, possibly because complement in itself inhibits the formation of the large ICs that would bind to C3b receptor-bearing cells. PMID- 2598645 TI - Alterations in the terminal complement pathway in leukopenic children with malignant diseases during episodes with evidence of infection. AB - A prospective study comprising 23 children under treatment with cytostatic drugs for malignant diseases was undertaken to search for complement abnormalities during episodes with evidence of infection. Eleven patients developed 17 episodes with fever (temperature greater than or equal to 38 degrees C) (n = 13) and/or increased concentration greater than or equal to 10 mg/l) of C-reactive protein (CRP) (n = 16). Complement factor C9 increased significantly (greater than or equal to 150%) in 12/13 of the events with fever, in 16/16 with increased CRP, and in 1 additional event with normal temperature and CRP concentration. The terminal complement complex (TCC) increased excessively (37.2 units/ml) parallel to a fall in C9 and S-protein in a single patient with a lethal septic shock, and was slightly increased (2.9 units/ml) in a 2nd case who was efficiently treated. These were also the only 2 cases with verified bacterial infections. We conclude that C9 is a valuable supplement to CRP for detection of events with probable infection and that TCC is increased only in severe infection and may be of prognostic importance. PMID- 2598647 TI - The murine local lymph node assay for identification of contact allergens: a preliminary evaluation of in situ measurement of lymphocyte proliferation. AB - A murine local lymph node assay for the identification of contact allergens has been developed. Contact sensitizing activity is measured as a function of lymphocyte proliferation in the draining lymph node following repeated application of the test agent to the dorsum of the ear. In original studies, lymphocyte proliferative activity was measured in vitro. In an attempt to remove the requirement for tissue culture, and thereby enhance the utility of the local lymph node assay as a predictive screening method, a new protocol has been evaluated in which proliferation in draining nodes is measured following i.v. injection of 3H-thymidine. PMID- 2598648 TI - Allergic contact dermatitis from croconazole hydrochloride. AB - We report 6 cases of contact sensitivity to croconazole hydrochloride, a new imidazole antimycotic drug introduced to the Japanese market in 1986, and available as 1% gel and cream. 6 sensitized patients reacted on patch testing to croconazole hydrochloride down to 0.5 to 0.1% pet, and 3 appeared to be cross sensitized to sulconazole nitrate. In Japan, allergic contact dermatitis to this drug has now been detected in 12 cases, including our own 6. Prescribers should be aware of contact sensitivity to this drug. PMID- 2598649 TI - Evaluation of a non-invasive human and an in vitro cytotoxicity method as alternatives to the skin irritation test on rabbits. AB - 5 substances were investigated for their primary irritant effect by means of different protocols. The cutaneous blood flow values (CBFV) were measured in humans: in a 1st series of experiments 12 h after application of the pure substances for 48 h and in a 2nd series of experiments 1, 24, 48 and 72 h after application of the 10% diluted substances (subclinical concentration) for 3 h. Rabbit skin erythema scores were obtained 1, 24, 48 and 72 h after application of the undiluted substances for 4 h. The uridine uptake inhibition assay on KB cells was included as a cytotoxicity test. Results obtained for both protocols on humans are compared with each other and with the test data obtained on rabbits, and with the cytotoxicity data. Application of the undiluted substances for 48 h on human skin or for only 3 h at a 10% dilution resulted in the same ranking between the substances. The CBFV in the human correlated very well (r = 0.99) with erythema scores obtained on rabbits. A poor correlation was observed between the in vitro and the in vivo results. From this study, it can be concluded that CBFV measurement is a valid method for the detection of erythema at subclinical concentrations. PMID- 2598650 TI - Nickel dermatitis from cheap earrings. AB - In 1988, 64% of our patients patch test positive to at least 1 allergen of the ICDRG standard series were nickel sensitive. In 70% of 300 patients evaluated, dermatitis started on the earlobes and was related to the regular wearing of cheap earrings. At the same time, 62% of 735 young schoolgirls were found to have dermatitis of their earlobes and all regularly wore cheap earrings. 9 clasps and clips commonly used in earrings released high quantities of nickel ions (between 49 and 103 micrograms/12 h), having been stored in synthetic sweat. A round piece cut from a clasp was taped to the skin of 30 nickel-sensitive patients, previously tested with 20 microliters of NiSO4 5%, 2.5%, 1% aq. solutions, giving a response similar to that caused by the 5% solution. High daily absorption of Ni ions through the skin follows its repetitive exposure to cheap earrings, causing, firstly, a direct inflammatory reaction, then followed, in our opinion, by sensitization. PMID- 2598651 TI - Patch testing in actinic prurigo. AB - 42 out of 93 Saskatchewan Indians (32 female (F) and 10 male (M] with actinic prurigo were patch tested to standard series allergens between 1983 and 1987. Positive reactions were most frequently seen with nickel (3F:2M) and colophony. All 3 positive patch tests to colophony were in males. The same patients were also patch tested to extracts of 21 Saskatchewan plants and 3 Hollister-Stier plant extracts. Only 1 male and 2 females had positive patch tests. None of these 3 had rashes on the eyelids, behind the ears or under the chin. We conclude that plant contact dermatitis is unlikely to be mistaken for actinic prurigo in Saskatchewan. PMID- 2598652 TI - The intra- and inter-individual variability and reliability of transepidermal water loss measurements. AB - An analysis of variance was conducted to estimate the intra- and inter-individual variations in TEWL on the forearms, by sites (8 measurement sites) and by days (10 different days), in 30 non-exposed healthy individuals. The estimated intra- and inter-individual variations, by sites, were 15.5% and 84.5%, respectively, the sum of the 2 components always being 100%. With the exclusion of the 2 most distal sites near the wrist, which had significantly higher baseline TEWL values and fluctuations in TEWL, an improvement in the intra-individual variation was obtained. Thus, of the 6 sites, the estimated intra- and inter-individual variations were 8.4% and 91.6%, respectively. This finding supports the exclusion of these most distal sites for future investigations. The estimated intra- and inter-individual variations, by days, were 20.6% and 79.4%, respectively. The low site-to-site (8.4%) and day-to-day (20.6%) intra-individual variations, as compared to the large inter-individual variations of the same (91.6% and 79.4%), indicate that baseline TEWL is a stable personal characteristic. Thus, individual susceptible to irritant contact dermatitis (ICD), due to occupational exposure, may be reliably characterized by utilizing their baseline TEWL values, for "prediction" of risk in epidemiological field studies. PMID- 2598653 TI - Percutaneous absorption of 3 organic solvents in the guinea pig (IV). Effect of protective gloves. AB - The efficacy of 3 protective glove materials against percutaneous absorption of organic solvents was investigated in the guinea pig. All 3 materials gave a reduction in blood concentration of the solvents, particularly in the early phase of exposure. Of the tested materials, butyl rubber showed the best protective effect, followed by PVC and natural rubber. Gloves of polymeric material can be considered as offering sufficient protection against percutaneous absorption of organic solvents only if their selection is based on results obtained in a controlled and adequately performed test. PMID- 2598654 TI - Allergic contact dermatitis from shoes: "angry back" without "angry thigh". PMID- 2598655 TI - Propolis allergy: synthesis and patch testing of gamma,gamma-dimethylallyl caffeic acid ester and its o-methyl derivatives. PMID- 2598656 TI - Hexamidine isethionate: a sensitizer in topical pharmaceutical products and cosmetics. PMID- 2598657 TI - Histological examination of immediate and delayed contact allergy provoked by mercuric chloride. PMID- 2598658 TI - Allergic granuloma from cosmetic eyebrow tattooing. PMID- 2598659 TI - Effects of skin sensitization test wrapping on guinea pigs. PMID- 2598661 TI - Carbamazepine and patch testing. PMID- 2598660 TI - Pure abietic acid is not allergenic. PMID- 2598662 TI - Major "enamelin" protein in enamel of developing bovine teeth is albumin. AB - The major, non-amelogenin protein component (enamelin) present in EDTA or EDTA-GU HCl extracts of developing bovine enamel has a molecular weight of approximately 67 kD and an amino acid composition rich in asp, glu, ala, leuc and lys. Elution of this component from 1.5 and 3.0 mm thick strips SDS-PAGE gels and subsequent analyses show that the component selectively reacts with polyclonal antibody to bovine serum albumin. Absolute identification of this major enamelin component as serum albumin is established by an amino acid sequence of the first 40 N-Terminal amino acids which was found to be identical to bovine serum albumin. In addition to albumin, alpha-2 HS glycoprotein was also identified in the same extracts by Western blotting against a monospecific polyclonal antibody against human alpha-2 HS glycoprotein. PMID- 2598663 TI - Enamelins and amelogenins share the same amino-terminal sequence. AB - Previous results from our laboratory indicated that rabbit enamel high molecular weight proteins have the same amino-terminal sequence that amelogenins, thus suggesting the possibility that this domain is shared by both, enamelins and amelogenins. To determine if this is true for other species, enamel proteins and mRNA were extracted from rabbit and hamster developing teeth and analyzed using probes targeted towards the N-terminal sequence of the amelogenins. Our results strongly suggest that both, enamelins and amelogenins share the same amino terminal amino acid sequence. PMID- 2598664 TI - Secondary structure and limited three-dimensional structure of bovine amelogenin. AB - Secondary structural features of bovine amelogenin, a hydrophobic protein of developing enamel implicated in ename mineralization, are derived using 2D NMR spectroscopy in solution and molecular mechanics-dynamics studies. A beta-turn: beta-sheet model with some "unordered" segments was previously proposed from circular dichroism, Fourier-transform infrared and Raman spectroscopy augmented by Chou-Fasman predictive algorithm. The proposed structure contains a repetitive beta-turn segment, "beta-spiral" between Gln112 and Leu138 residues containing a (Pro, Leu, Gln) rich segment. The beta-spiral structure offers a probable site for interaction of Ca++ ions. Assignment of proton resonances using 2D COSY spectroscopy is presently in progress. Preliminary 2D NOESY spectra have revealed the presence of Tyr residues (TRAP segment) on the surface of amelogenin molecule and clusters of cross peaks reminiscent of beta-turns and sheets which are consistent with the primary structure and proposed secondary structures of amelogenin. The channel-like beta-spiral structure embedded in amelogenin provides a novel mechanism for trapping of Ca++ ions and their passage for a hydrophobic protein sparse in Ser(P) and charged amino acid residues. PMID- 2598665 TI - Control of crystal growth during enamel maturation. AB - Attempts to promote crystal growth in maturation stage enamel from rat incisors were carried out by incubation in saturated solutions of calcium phosphate. Resulting crystallites were visualised in the TEM and the dimensions of their profiles measured. No crystal growth was observed unless the maturation stage enamel was first pretreated with either 8M urea or sodium hypochlorite to remove residual protein matrix. The results suggest that the protein matrix plays an important role in the control of crystal growth in vivo. PMID- 2598666 TI - Secretory activity as a function of the development and maturation of ameloblasts. AB - The biosynthetic and secretory activity of rat incisor ameloblasts was studied by grain count analysis of radioautographs at various times following a single injection of either 3H-methionine, 3H-leucine, or 3H-glycine. Experiments were also carried out with leupeptin, a thiol and serine proteinase inhibitor which blocks degradation of proteins within lysosomes. The results from this study indicate that the biosynthetic and secretory activities of ameloblasts increase steadily as the cells differentiate (presecretory stage) and start to form the enamel layer (secretory stage). Secretory activity reaches a peak when the ameloblasts form about one-third of the eventual thickness of the enamel, and remains at this high level until shortly before they start to form the outer and final layers of enamel. Secretory activity then drops rapidly as the cells undergo postsecretory transition, and declines slowly thereafter as the shortened ameloblasts modulate continuously along the surface of the maturing enamel. Ameloblasts appear to biosynthesize more proteins than are secreted. The excess proteins are degraded rapidly in lysosomes and the amino acids reutilized for production of new exportable and/or structural proteins. PMID- 2598667 TI - Calbindins D-9kDa and -28kDa and enamel secretion in vitamin D-deficient and control rats. AB - The present study focuses on the ultrastructure of enamel organ cells and the immunolocalization of calbindins D-9kDa and -28kDa during enamel secretion in Vitamin D-deficient rats. Vitamin D-deficiency disturbed the deposition of the layer of inner enamel and depleted the calbindins-content of ameloblasts. These data raise the possibility of a direct action of Vitamin D on the physiology of ameloblasts through ionic calcium homeostasis. PMID- 2598668 TI - Alkaline phosphatase cDNA transfected cells promote calcium and phosphate deposition. AB - The full length cDNA of rat alkaline phosphatase (AP) was placed under the control of the SV40 early promoter. This plasmid was transfected by the calcium phosphate method into AP negative ROS 25/1 cells. Ten clones with AP specific activities ranging between 0.1-2 mumole/min/mg were isolated by cotransfection with the plasmid pSV2Neo, which renders the cells resistant to the antibiotic G418. Two clones with different AP specific activities: C (0.01 mumole/min/mg) and S (2.0 mumole/min/mg) and the osteoblastic ROS 17/2.8 cells (2.0 mumole/min/mg), were examined for their ability to mineralize. In vitro mineralization was tested by culturing cells in alpha-MEM containing 10% fetal bovine serum and 50 micrograms/ml ascorbate in the presence or absence of 10 mM beta-glycerophosphate. Mineralized deposits were observed in all cultures of the S clone and ROS 17/2.8 cells in the presence of beta-glycerophosphate, but not in C clones. Measurement of calcium and phosphorus levels in cells correlated with AP levels of transfected cells. However, extent of mineral accumulation in the transfected ROS 25/1 cells differ from the osteogenic ROS 17/2.8 cells. This finding indicates that high levels of AP may be a necessary constituent for the mineralization process together with other factors yet to be identified. PMID- 2598670 TI - Histochemical properties of the "crystal ghosts" of calcifying epiphyseal cartilage. AB - The crystal ghosts represent a crystal associated organic material which is stained by acidic phosphotungstic acid, periodic acid-silver methenamine and periodic acid-thiosemicarbazide-osmium, and is reactive with cations and with colloidal iron at pH 2.0, and unreactive after methylation and saponification. These results suggest that crystal ghosts are, or derive from, proteoglycans of calcifying matrix. PMID- 2598669 TI - Vesicle- and collagen-mediated calcification in the turkey leg tendon. AB - The distribution, organization, and orientation of apatitic mineral associated with vesicles and collagen in normal calcifying turkey leg tendon have been examined to determine inorganic-organic interactions in this vertebrate tissue. The study utilized selected area electron diffraction and bright or dark field transmission electron microscopy of thin sections (approximately 70 nm) treated by anhydrous means. Bright field microscopy revealed crystals randomly disposed in radial clusters related to vesicles or highly oriented related to collagen. Dark field images of the crystal c-axis were localized within some hole zone regions of collagen but were generally sparse in vesicles. Images of mineral a,b axes were associated with vesicles and also appeared in collagen hole zones complementary to those containing c-axis images. Where mineralization of vesicles occurred adjacent to that of collagen, bright and dark field images provided suggestive evidence that the crystals could be contiguous at some sites, but the bulk of extracellular mineralization was spatially discontinuous. The varying disposition of mineral in vesicles and collagen is likely indicative of distinct mechanisms of nucleation in these components, the complementary orientation of mineral c- and a,b-axes in collagen may provide insight into the structure and organization of the protein, and the distribution of vesicle-mediated mineralization appears to contribute to apatite accumulation between collagen fibrils. PMID- 2598672 TI - Diabetes and the kidney. 24th Workshop for Dialysis Physicians. March 10-12, 1988, Prien, Chiemsee. Proceedings. PMID- 2598671 TI - Characterization of extracellular and nascent dentin phosphoproteins. AB - Experiments were designed to compare extracellular dentin phosphoprotein (DPP) and nascent DPP prior to post-translational modifications from several vertebrate species. Dental matrix proteins were extracted with acetic acid, followed by GuHCl-EDTA, and precipitated with CaCl2. Cross-reactivity of the DPPs with a mouse DPP antibody was determined by a dot-immunobinding assay. To analyze nascent DPP, mRNA was isolated from developing tooth organs and the mRNA-directed translation products were immunoprecipitated with the DPP specific antibody. All DPP components identified in the species which contained a DPP were shown to cross-react with the polyclonal mouse DPP antibody. The extracellular matrix DPPs were found to exhibit as much as a 30 kDa size difference using the same SDS PAGE system. In contrast, nascent DPPs were found to be the same size for all species examined. Our results indicate that differences in the molecular weight size of DPPs between species may be due to the degree of post-translational modifications such as phosphorylation. PMID- 2598673 TI - Autonomic neuropathy in diabetic nephropathy. Effect of regular dialysis treatment and simultaneous transplantation of kidney and pancreas. PMID- 2598674 TI - Long-term outcome in diabetic patients on hemodialysis treatment. PMID- 2598675 TI - Treatment of end-stage renal insufficiency in diabetic nephropathy by hemofiltration. PMID- 2598676 TI - Results of peritoneal dialysis in diabetics. PMID- 2598677 TI - Tolerance of human corneal endothelium to glycerol. AB - As an initial step in the development of a method for corneal cryopreservation by vitrification, we attempted to establish the maximum concentration of glycerol to which human corneal endothelium could be exposed at 4 degrees C for 15 min without damage. Damage was defined as an increase in mean endothelial cell size or the inability to maintain corneal thickness for 1 week after exposure to glycerol. Using a system for long-term corneal perfusion, we perfused 24 paired human corneas with glycerol at 4 degrees C. The concentration of glycerol increased at a rate of 20% (w/v) (2.2 M) per hour until the desired maximum concentration was reached for that cornea, stabilized for 15 min, and then decreased at the same rate. The corneas were then perfused at 37 degrees C with Dulbecco's medium at a rate of 5 microliters/min under 18 mm Hg intracameral pressure for 7 days with daily measurements of corneal thickness. Endothelial morphology was examined by specular microscopy and by scanning electron microscopy. After 7 days of perfusion at 37 degrees C, there was a statistically significant direct relationship between the maximum concentration of glycerol to which the experimental eyes had been exposed and the increase in mean endothelial cell size. The mean endothelial cell size increased in corneas exposed to glycerol concentrations of 40, 50, and 60% (w/v), but did not differ significantly from baseline measurements in the corneas exposed to 30% glycerol or less. Thus, there was no detectable damage to human corneas exposed to 30% (w/v) (3.3 M) glycerol in this system. Tolerance of higher concentrations may be achieved by changes in the rates of addition and removal of glycerol or in the composition of the perfusate. PMID- 2598678 TI - Abstracts of papers presented at the twenty-sixth annual meeting of the Society of Cryobiology. June 11-16, 1989, Charleston, South Carolina. PMID- 2598679 TI - Protecting yourself from AIDS: infection control measures. PMID- 2598680 TI - Gas gangrene: certain diagnosis or certain death. AB - Clostridia are organisms which, in the right environment, can cause a rapidly spreading, fulminant myonecrosis. Early diagnosis and a combined management program are clearly paramount to a successful outcome. Knowledge of this disease and ongoing meticulous assessment are the tools that a nurse must use when dealing with patients who have gas gangrene or are at high risk of developing it. In the face of radical disfigurements that may follow therapeutic measures, the potential transfer to a distant center for treatment, and a deteriorating prognosis, the nurse must remain alert to patient and family psychologic needs. PMID- 2598681 TI - Near drowning: a nursing challenge. AB - The victim of near drowning is one who presents multisystem problems for the critical care nurse. By understanding and recognizing the interrelationships of the problems that these individuals have, the nurse will be better able to meet the challenges presented. PMID- 2598682 TI - Acute brain failure in the critically ill patient. PMID- 2598683 TI - Alternating bundle branch block. PMID- 2598684 TI - Stellate- and foci-formation of mouse fibroblast cells transfected with various cancer cell DNA. AB - Two methods of DNA-mediated gene-transfer, namely, CaPO4 co-precipitation and polybrene/DMSO-induction were used to analyse oncogenes from various cancer cell lines. Third time transfection of mouse fibroblast cells, NIH/3T3 with 10, 100, 1,000 and 3,000 ng of DNA from spontaneous human hepatoma cells produced 41, 4, 45 and 56 foci, respectively. It appears that 100 ng of this hepatoma cell DNA gave the least effective transformation ability. However, with two spontaneous mammary cancer cell lines, 100 ng DNA gave the highest number of foci. In general, during the initial transfection, the cells appeared semi-transformed, showing stellate growth patterns. With repeated transfections they gave way to foci. However, with aflatoxin-induced rat hepatoma cell (JB-1) DNA, only stellate growths persisted to indicate intermediate transformation. Transfection of the epithelial-like normal rat liver cell line, BL8 with JB-1 DNA produced haphazard growth pattern, although a hepatoma-associated enzyme, gamma-glutamyl transferase was introduced into the BL8 cells which previously had no detectable enzyme activity. PMID- 2598685 TI - Morphology of the pig's pineal gland from 8th to 16th week of foetal life. AB - Pineal glands of the pig from the 8th to the 16th week of foetal life were examined by means of both light and electron microscopy, and changes in the pineal structure were observed. The pinealocyte structure manifests the secretory activity of the pineal gland at the time of examination. PMID- 2598686 TI - Lactate dehydrogenase isozymes in xenotropic virus producing mice. AB - Lactate dehydrogenase (LDH; E.C. 1.1.1.27) isozymes were compared in three inbred strains of mice, and two strains of wild mice, as well as the F1 hybrids and other genetic crosses involving two of the inbred strains. The strains examined were NZB/B1NJ, 129/J and C57BL/6J, Mus musculus molossinus and M. musculus castaneus. Genetic crosses were made between the xenotropic virus-producing NZB and the non-virus producing 129/J mice. Tissue specificity of LDH in these strains was studied using homogenates of kidney, liver, spleen and thymus. Polymorphism of the enzyme was studied by agarose gel electrophoresis. Enzyme polymorphism in the tissues of NZB and 129/J has not been previously reported. The liver and spleen tissues of 129/J showed the absence of LDH-1 and LDH-2 isozymes. Thymic homogenates of NZB showed a lack of expression of LDH-1, LDH-2 and LDH-3 isozymes. The F1, F2 and the backcross progeny from genetic crosses involving NZB, and 129/J mice showed an isozyme pattern more similar to the non virus-producing 129/J strain than the virus-producing NZB. Evidence of genetic regulation at the LDH-B subunit appears to be the reason for the differential expression of the isozymes in NZB and 129/J strains. The other inbred strain of mice, C57BL/6J, also showed a greater similarity to the 129/J strain than NZB. The two strains of wild mice were similar in their expression of LDH-isozymes between each other and to the 129/J strain, with respect to the liver and spleen tissues. PMID- 2598687 TI - [The maxillary sinus: anatomy, physiology, relation to implantology]. PMID- 2598689 TI - [The role of nuclear magnetic resonance spectroscopy in implantology]. PMID- 2598688 TI - [Metals and metal alloys used in implantology. Physico-chemical aspects]. PMID- 2598690 TI - [The VB Vital Bleaching method. Effect of chemical treatment on enamel]. PMID- 2598691 TI - [Occlusal preparation in implantology]. PMID- 2598692 TI - [Indications and technic for the ramus frame implant (R.F.I.)]. PMID- 2598693 TI - [Biocompatibility of titanium and its alloys]. PMID- 2598694 TI - [Choice of technic for placement of osseointegrated implants]. PMID- 2598695 TI - [Premedication for dental surgery]. PMID- 2598696 TI - [Implant treatment of the totally edentulous mandible]. PMID- 2598697 TI - [The CO2 laser and gingivoplasty]. AB - The CO2 laser has here been used in comparison with the electric bistoury during a gingivoplasty joined to a subgingival scaling. The healing up and the result - in a short as well as in a long length of time - are the same. This type of laser can then be used in this sort of treatment despite the fact that it does not bring any particular advantages. PMID- 2598698 TI - [The tooth-amalgam joint: the role of the marginal bevel]. AB - Three amalgams, Standalloy, Dispersalloy and Formibel are used to fill class I cavities (bevelled or not) and applied over fresh-removed wisdom teeth. Macroscopic examination with a binocular lamp shows a better marginal adaptation of amalgams when cavity walls and edges have no asperity nor bevel and regardless of the quality of the amalgam. This MEB examination reveals a gap at dentinal level that might result from the vacuum processing of the samples. PMID- 2598699 TI - [What to choose? Clinical options and seal of silver amalgams]. PMID- 2598700 TI - [Choice of functional dental equipment]. PMID- 2598701 TI - [Cariology concepts]. PMID- 2598702 TI - [The clinician and caries. Self-test of his diagnostic method]. PMID- 2598703 TI - [Rampant caries: preventive and restorative therapy]. PMID- 2598704 TI - [Caries in the child and adolescent]. PMID- 2598705 TI - [Periodontal considerations in treatment of caries-susceptible patients]. PMID- 2598706 TI - [Clinical and therapeutic approach to corono-radicular and radicular carious lesions]. PMID- 2598707 TI - Dentists argue over TMJ arsenal. PMID- 2598708 TI - Common errors occur with 'easy' laminates. PMID- 2598709 TI - Operatory clothing fends off bacteria. PMID- 2598710 TI - Case selection illuminates 'mystery' of vital bleaching. PMID- 2598711 TI - Implant overdentures relieve discomfort for the edentulous. PMID- 2598713 TI - The 4 Ws of implants clarify diagnosis. PMID- 2598712 TI - Anterior implants replace incisors. PMID- 2598714 TI - Experts bless heat-cured systems. PMID- 2598716 TI - Seeing the way to better care. PMID- 2598717 TI - Disposal tips help dump waste safely. PMID- 2598715 TI - Esthetic makeovers focus on smile line. PMID- 2598719 TI - Enact asepsis, but keep it easy. PMID- 2598718 TI - Analysis of medical history pinpoints conditions that contraindicate implants. PMID- 2598720 TI - Evidence indicates dentin exposure may not harm pulp. PMID- 2598721 TI - Communication gap imperils implants. PMID- 2598722 TI - Implants face stiffer regulation. PMID- 2598723 TI - Etched porcelain veneers hit the mark for quality. PMID- 2598724 TI - Misconceptions obscure purpose of infection-control procedures. PMID- 2598725 TI - [A comparative study of EEG in patients with neurological and myxedematous cretinism]. AB - A comparative study of EEG between neurological and myxedematous cretins was carried out in a total of 61 cases. The results were as follows: (1) The changes of EEG in myxedematous cretins appeared to be more obvious than those in neurological cretins; (2) The degree of mental retardation in cretins was not parallel to the degree of the abnormality of EEG; (3) with thyroid therapy, EEG in cretins was improved. The improvement rate in myxedematous cretins was higher than that in neurological cretins; (4) Brain CT scan was carried out in 50 cases of those cretins. It was found that the abnormality of certain intracerebral structure in myxedematous cretins appeared to be more obvious than that in neurological cretins. The change of EEG appeared in the same way as well. This is in contradiction to the traditional knowledge that the defect of neurological system in neurological cretinism was more severe than that in myxedematous cretinism. The current classification of cretins into neurological and myxedematous cretins does not reflect the changes of pathophysiology properly. PMID- 2598726 TI - [Damage to the development of the rat brain by severe iodine deficiency and the protective effects of thyroid hormone]. AB - The detrimental effects of iodine deficiency on brain development and the protective effects of thyroid hormone replacement therapy in the critical period were closely examined. Animals in the experiment were divided into four categories: Normal control (NL), Low iodine diet group (LI), Normal iodine diet group (NI) and the thyroid hormone supplement group (LI+T). Results showed that the body weight, motility and the indices of learning ability including total time (TT), the number of conditioned reflex (CL), conditioned and unconditioned reflex latency and the correction rate of conditioned reflex in the LI+T were all improved to such a condition that there was no significant difference between the LI+T and N, NI. (P greater than 0.05), whereas there did have significant difference between LI+T and LI (p less than 0.01). The experiment confirmed the protective effects offered by the thyroid hormone from damaging by severe iodine deficiency. PMID- 2598727 TI - [Diagnosis of pulmonary hypertension by pulsed Doppler echocardiography- comparison with cardiac catheterization]. AB - 31 patients undergoing diagnostic cardiac catheterization for suspected congenital heart disease and 30 normal subjects were examined by pulsed Doppler echocardiography. Spectrum analysis of the shape of flow velocity curve and instantaneous flow velocities of the pulmonary artery during systolic period was made and their ratio calculated. The results showed that there was a remarkable difference between the flow velocity curve of pulmonary hypertension (PH) and that of normal pulmonary pressure. Combining with the characteristics of pulmonary arterial hemodynamics, a preliminary exploration was made on the mechanism of flow velocity curve changes. A ratio of flow velocities--PV% was proposed. The sensitivity and specificity for diagnosing PH with PV% were 94% and 100% respectively. There was a high correlation between PV% and pulmonary artery systolic pressure (r = -0.84) or pulmonary artery mean pressure (r = -0.82). It is concluded that PV% may eliminate many factors that influence the pulmonary artery hemodynamics and is a reliable, practical qualitative and quantitative index for diagnosing PH noninvasively. PMID- 2598728 TI - [Analysis of 128 cases of multiple myeloma and 31 cases of monoclonal gammapathies of undetermined significance]. AB - Monoclonal immunoglobulin from 138 patients with multiple myeloma (MM) showed that 68 patients were of IgG type, 23 of IgA type,33 of BJ type, 6 of IgD type, one of IgM type, 5 of nonsecreting type and the remaining 2 of IgA and IgG double monoclonal type. Urinary Bence Jones protein was tested with concentrated urine specimen with a positive rate of 75%. Classification of light chain revealed the ratio of oK/L being 1.09:1. The difference of distribution of K or L among IgG, IgA BJ types was no significant. 31 cases with monoclonal gammapathies of undetermined significance (MGUS) were also analyzed in this study. There were some difficulties in the differential diagnosis of MGUS and MM,but a significant difference was present in the plasma cell percentage of bone marrow smear of the two groups. Dynamic investigation in this series showed that patients with percentage of plasma cell less than 10% persisting for a long duration are likely to have MGUS only. PMID- 2598729 TI - [Causes of death and prognosis of myocardial infarction in patients with diabetes]. AB - The long-term prognosis and causes of death of myocardial infarction (MI) in 62 patients with diabetes were studied. The mean follow-up time was 6.2 years. 11 cases died in the acute period of MI (8 weeks following onset of AMI), 9 cases of them (81.8%) had anterior infarction and their major causes of death were ventricular fibrillation and cardiogenic shock (72.2%). 19 cases died in the follow-up period, among them 14 cases (73.68%) had inferior and anterior-septal infarction; most of them died of reinfarction and sudden death. The cumulative survival rate 1.2 and 5 years after MI was 80.7%, 71.9% and 57.9%, respectively. The blood glucose level of the fatal group and the level of CPK and GOT of patients who died in the acute period were higher than those in the surviving group. The results suggest that treatment of myocardial infarction in patients with diabetes be more attentive to prevent ventricular fibrillation and cardiogenic shock during the acute period. After the acute period more attention should be paid to prevent reinfarction and and drop the blood glucose level at normal as possible. PMID- 2598730 TI - [Analysis of urinary citrate and oxalate in 42 diabetics]. AB - Among 42 diabetics, there were 32 with the disease remaining uncontrolled after treatment. Their fasting blood glucose was 15.24 +/- 5.37 mmol/L (mean +/- S), urinary glucose 42.6 +/- 47.83 g/24 hr, urinary oxalate 0.43 +/- 0.16 mmol/24 hr and urinary citrate 3.60 +/- 2.28 mmol/24 hr All of these levels were higher than those in a control group (P less than 0.001). Urinary citrate level was significantly positively correlated with fasting blood glucose level (gamma = 0.3954, P less than 0.001). In the remaining 10 diabetics with the disease controlled after treatment the fasting blood glucose was 7.04 +/- 0.92 mmol/L, urinary citrate 1.92 +/- 0.96 mmol/24 hr and urinary oxalate 0.37 +/- 0.11 mmol/24 hr. All of these levels were significantly lower than those before treatment (P less than 0.01) and were not different from those in the control group (P greater than 0.05). This explains that urinary citrate and oxalate increased when diabetes is uncontrolled as a result of accelerated decomposition due to increased metabolism. Urinary oxalate level is correlated positively with that of urinary citrate (gamma = 0.3773, P less than 0.05). Urinary oxalate and citrate are good index reflecting diabetic metabolic changes. Analysis of urinary oxalate with ion-chromatography is accurate and rapid method worthy to be used clinically. PMID- 2598731 TI - [Efficacy of ofloxacin in treating typhoid fever]. AB - We studied 75 patients (36 males and 39 females), suffering from typhoid fever. 64 patients were treated with ofloxacin and 11 with amikacin, dosage regimens of the two drugs were 300 mg and 300-400 mg twice daily. Clinical effective rate was 100% with ofloxacin and 36.4% with amikacin. A total of 72 strains of salmonella typhi was isolated from all the patients of both groups. Bacteriological elimination rate was 100% with ofloxacin after treatment. Sensitive rates for S. Typhi isolated was 100% with ofloxacin, norfloxacin and ceftriaxone, 98.6% with amikacin and 20-21.4% with chloramphenicol, ampicillin and sulfamethoxazole Co. There were fewer adverse reactions and better acceptance, one had skin rash and one had gastrointestinal disturbance. In amikacin group, abnormality of urine routine and serum creatinine was observed. Ofloxacin was well absorbed orally. Its high bioavailability, satisfactory therapeutic efficacy excellent tolerability and convenience for use make it a very useful medication in the therapy of typhoid fever resulted from multiresistant strains. PMID- 2598732 TI - [Changes in peripheral leukocytic glucocorticoid receptor in patients with ischemic and hemorrhagic stroke]. AB - The maximal binding capacity (Ro) and dissociation constant (Kd) of glucocorticoid receptor (GCR) in peripheral leukocytes were estimated by radioligand binding method and the plasma cortisol levels measured in 25 stroke patients (hemorrhagic 15, ischemic 10), compared with 12 healthy controls, the plasma cortisol level in stroke patients were significantly higher. The plasma cortisol level of 15 hemorrhagic and 10 ischemic stroke patients and 12 controls determined by RIA were 1.12 +/- 0.21, 0.90 +/- 0.28 and 0.45 +/- 0.09 nmol/L respectively. Ro of leukocytic GCR in hemorrhagic stroke were significantly lower than that of ischemic stroke and controls. No difference was found between ischemic stroke and controls. No difference was found between ischemic stroke and controls. Ro of GCR in 15 hemorrhagic stroke, 10 ischemic stroke patients and 12 controls were 3496 +/- 424, 5678 +/- 1101 and 5940 +/- 763 sites/cell respectively kd of GCR were 10.47 +/- 4.17, 7.01 +/- 3.24 and 5.81 +/- 1.05 nmol/L respectively. Affinity of GCR in 15 hemorrhagic stroke patients was significantly lower. In conclusion, lower number and affinity of leukocytic GCR and higher plasma cortisol level were demonstrated in hemorrhagic stroke patients, but normal number and affinity of GCR and higher plasma cortisol level in ischemic stroke patients. PMID- 2598733 TI - [Clinical features and long-term outcome of 91 cases of adult onset post streptococcal glomerulonephritis in Hong Kong]. AB - The clinical features and long-term outcome of 91 cases of adult-onset PSGN in Hong Kong were reported. There were 46 male and 45 female with age ranging from 13 to 56 yrs (mean 18.6). The diagnosis was based on clinical manifestations and renal biopsy was performed in 29 cases. The main manifestations were acute nephritic syndrome (72.5%) and acute nephritic-nephrotic syndrome (27.5%). Serum creatinine was increased in 48.4% of the patients at presentation. Four cases presented with acute renal failure. Serial serum C3 levels were determined in 48 patients. It was decreased in all patients at presentation but returned to normal within 15 weeks. The follow-up duration of this series ranged from I to 19 yrs (mean 4.73 yr) 67.03% recovered early (within 3 mts); 14.29% recovered later (from 6 mts to 7 yrs): 16.48% had persistent or intermittent proteinuria and or haematuria. Two cases developed chronic renal insufficiency. Our results suggested that the prognosis of PSGN in adults is relatively good and the indications for renal biopsy in adult-onset PSGN were discussed. PMID- 2598734 TI - [Surgical treatment of acute intestinal obstruction caused by large bowel carcinoma]. AB - In the past 30 years 338 patients with colorectal carcinoma were admitted for acute intestinal obstruction which accounted for 17.17% of 1969 surgically treated colorectal carcinomas. Of these, right colon carcinoma was found in 116 cases, left colon carcinoma in 177, and rectal carcinoma in 45. Sixty nine one stage resections of the tumor out of 148 emergent operations were carried out including all 29 right colon carcinomas, 20 out 34 left colon carcinomas, and 4 out of 6 rectal carcinomas. In patients undergoing one-stage resections, the overall operative mortality was 3.77%, morbidity happened in one case suffering from anastomotic leakage, and the five year survival rate was 43.4% compared with no operative mortality, and five year survival of only 18.75% in delayed resection group. Our data showed that the mortality of one stage resection of left colon carcinomas complicated with acute obstruction was acceptable and the five year survival rate was slightly higher than that in delayed resection. In terms of whole series, the five year survival rate in one stage resection group was significantly higher than that in delayed resection group. The authors, therefore, favour one stage resection of the tumor in cases of acute intestinal obstruction. PMID- 2598735 TI - [Anal sphincter reconstruction by interposition of an ileo-colonic segment and transposition of musculi glutaeus maximus bundles after resection of anorectal carcinoma]. AB - From April 1983 to July 1987, 33 anorectal cancer patients were treated with segmental ileocolonic interposition and transposition of muscular bundles of musculi glutaeus maximus to reconstruct of anal sphincters after abdominoperineal resection of the carcinoma (Miles' operation). All patients were followed up for a half up to 3.5 years. The function of reconstructed anal sphincters was evaluated by fecal evacuating ability, by pressure measurement of the reconstructed internal and external sphincters, and by X-ray observation. The function was rated as good to perfect in all of the patients. PMID- 2598736 TI - [The Nd: YAG laser in the treatment of colonic polyps]. AB - The result of Nd: YAG laser therapy in 31 patients with pathologically verified rectosigmoid polyps was presented. Except one case with large adenomatous polyp recurring two months after the primary treatment, all other patients were cured clinically on their first therapy. There were no severe complications, and the longest follow-up period was 14 months. The authors came to the conclusion that compared with other modalities, Nd: YAG laser therapy is safe, effective, and low recurrence rate. PMID- 2598737 TI - [Diagnosis of smooth muscle tumor of the small bowel]. AB - In this report, the experience in the diagnosis of smooth muscle tumor of the small bowel in 32 cases (14 leiomyomas and 18 leiomyosarcomas) was presented. The authors discussed the clinical features, the pathological classification of the tumor, the diagnosis of intestino-intestinal fistula, and ways to improve its preoperative diagnosis. PMID- 2598738 TI - [Epithelioid leiomyoma of the gastrointestinal tract]. AB - This paper presents an analysis of 35 GI epithelioid leiomyomas (leiomyoblastoma) including the authors' own 6 cases from 1975 to the end of 1987. Tumors were found in the stomach in 21 cases (60%), in the duodenum in 4 (11.2%), in the jejunum in 7 (19.8%), and in the ileum in 3 (8.5%). The male to female ratio was 1:1.2 ranging in ages from 11 to 68 with an average of 42. Of these, 82.8% were benign and 17.2% were malignant. No case was correctly diagnosed before the operation. Tumors were resected in 97.2% of the patients. In the author's opinion there should be two basic types of the tumor: benign and malignant, though the identification is often quite difficult. The mitosis, the size of primary tumor, the metastasis and recurrence of the tumor should all come into the consideration. Surgical resection of the tumor is the only effective treatment and all tumors should be treated as malignant. PMID- 2598739 TI - [Abdominal cocoon]. AB - Two cases of abdominal cocoon are reported. Abdominal cocoon is rare, only 31 cases reported in the literature. The majority of the cases are adolescent girls with symptoms of acute or chronic intestinal obstruction and/or abdominal mass. Ultrasound examination shows the mass is a shadow of intestinal loop aggregation and barium meal reveal the mass to be made of folded intestine. Operative findings showed the bowel is encased in a white, tough and dense membrane that on microscopic examination thickened fibrous tissue are found Partiac. Removal of the membrane, releasing the intestine adhesions and plication of the bowel may be effective. PMID- 2598740 TI - [The determination of Cu and Zn levels in the serum and gastric juice of patients with gastric cancer]. AB - The serum copper and zinc Levels of 35 cases of gastric cancer were measured pre- and postoperatively, and Cu and Zn Levels in their gastric juice were also determined Preoperatively. The results Showed that serum copper Levels (SCL) and Cu/Zn ratios of patients with gastric cancer were significantly higher, while serum zinc levels (SZL) lower than those of the control. In addition, SCL of patients with gastric cancer elevated progressively as the cancer advanced. After resection of the tumor, SCL and Cu/Zn ratio declined and SZL elevated again. The Cu and Zn levels in the gastric juice, of benign gastric lesions showed more marked elevation and gastric cancer patients had higher Zn level than those in the normal controls. PMID- 2598741 TI - [Microvascular changes in the pyloric ring and duodenal invasion in carcinoma of the gastric antrum]. AB - In this study, vascular perfusion of surgically removed specimen was carried out in 45 middle or late staged gastric antrum carcinomas and 5 gastric ulcers to observe the morphology of the microvasculature at the juncture of the stomach and the duodenum. It was found that: 1) The microvasculature on both side of the pylorus and the duodenum communicated through small arteriole and the morphology of the microvasculature varied with tumor-infiltrated depth. 2) The duodenum was found to be invaded by the tumor in only 2 cases in which the tumor was within 1.5 cm from the pyloric ring. 3) The mechanism by which the tumor invaded the duodenum was most likely resulted from direct extension through the interstitium when the microvasculature, the physiological and anatomical intact of the pyloric ring were destroyed by the tumor. 4) Based on the aforementioned observations, the authors propose that in gastric antrum carcinoma, the safe resection length of the duodenum is less than 3 cm when the tumor is 1.5 cm away from the pyloric ring, otherwise, more than 3 cm of the duodenum should be removed. PMID- 2598742 TI - [Measurement of the length of the adult esophagus using a fiberogastroscope: 104 cases]. AB - From May 1979 to July 1985, the length of the esophagus in 104 patients with gastric disease was measured by a WX-C3 type fiberogastroscope. The result of measurement showed that the average length from the upper incisors to the cardia was 44.4 cm, and that from the upper end of the esophagus to the cardia was 28.0 cm. These measurement were respectively 4.4 cm and 3.0 cm longer than the traditional data (P less than 0.01). The difference in the length of the esophagus may be explained on the basis that measurement by rigid esophagoscope is in a straight line, while that by flexible fiberogastroscope is in a curvedline. Positive correlation between the length of the esophagus and the height of body was found in 91.3% of the cases. These data are of importance in the accurate localization of esophageal lesions. PMID- 2598743 TI - [Extracorporeal shock wave lithotripsy in renal calculi causing ureteral obstruction: report of 20 cases]. AB - From Dec. 1985 to July 1988, 2006 patients with renal calculi were treated with Zhongshan Hospital JT-ESWL-I and France EDAP machines. Post-treatment obstruction of ureteral street stones occurred in 20 patients (1% in this series) with large renal calculi: 10 cases occurred in the left ureter, whereas the others in the right. The length of street stones measured 3-22 cm. Among the 20 cases, 14 patients were cured by medicine, repeated ESWL, or/and endoscopical manipulation. Two patients with acute renal failure were completely free of ureteral stones after nephrostomy or placement of a ureteral catheter and irrigation. 2 patients are still under treatment. In addition, some factors of the formation, prevention and treatment of the ureteral street stones are discussed in this paper. PMID- 2598744 TI - [Internal carotid arterial BCNU perfusion in the treatment of cerebral glioma]. AB - From May 1984 to 1987, 19 patients of cerebral glioma were treated by internal carotid intra-arterial BCNU perfusion. Trans-carotid artery or transfemoral catheterization were performed in these patients. The single dosage was 100 mg/m2 and repeated every 4-6 weeks. 12 patients received more than two courses of perfusion and had follow-up study. Previously partial resection of the tumor underwent in 10 cases and also receiving radiation therapy in 6 of them. The remaining 2 patients only biopsy were performed. There was no mortality. But severe complications occurred in two patients, one loss of vision on the injected side and the other contralateral hemiplegia. The result of chemotherapy were defined as "complete response" in two patients, "partial response" in five, "no change" in three and deterioration of disease in two. The authors concluded that internal carotid intra-arterial BCNU chemotherapy is effective, my be used as an adjunctive treatment of cerebral gliomas. PMID- 2598745 TI - [Intracranial arachnoid cyst: report of 23 cases]. AB - Twenty-three cases of intracranial arachnoid cyst are reported. Among them 8 cases developed primarily and 15 secondarily. There are 19 male and 4 female, ages ranged 3 to 40 years. The duration of illness were one month to 32 years. There are 19 cases located supratentoriumly and 4 subtentoriumly. Most of them were situated at Sylvius fissure (13 cases). 22 cases were treated by partial resection of the cyst and different kinds of shunt operations. Short-term follow up study showed that the results were excellent without operative death. The etiology, pathogenesis, diagnosis of this disease and operative indications are discussed. PMID- 2598747 TI - [Treatment of complications of complete dislocation of the knee joint]. AB - 12 cases of complete dislocation of knee joint were reported. Of them, 5 were anterior, 3 posterior, 2 rotational and the remaining 2 were uncertain. Neurovascular complications occurred in 5: 3 with injury of popliteal vessels, 2 with injury of peroneal nerves. The limbs of the cases with vascular injury were all saved after repair of the vessel in 2, and following conservative treatment in 1. Surgical repair of cruciate and collateral ligaments as well as the capsule were properly carried out in 11 cases, in early due time. One of them has also had peripheral tear of meniscus which was repaired incidentally. Follow-up study showed excellent and good result in 9 cases. Points of operative indications were discussed. PMID- 2598746 TI - [Surgical treatment of patient ductus arteriosus associated with pulmonary hypertension under cardiopulmonary bypass]. AB - From July 1985 through December 1987, 30 patients with PDA and pulmonary hypertension were treated surgically under cardiopulmonary bypass. 17 cases underwent closure of PDA through transpulmonary arterial incision and 13 cases by ligation of PDA. The operative mortality was 3.3% and there was no late death. Follow-up study from 6 months to 3 years after operation showed satisfactory results. PMID- 2598748 TI - [Phrenic nerve transfer treating root avulsion of the brachial plexus]. AB - 164 patients with injury of root avulsion of the brachial plexus was treated by way of ipsilateral phrenic nerve transfer through a time period from 1970 to 1987. The among 65 cases that had been followed up for 2-13.5 years on average, 55 cases (84.6%) regained muscular strength of 30 or more. None of the patients had any subjective feeling or objective signs of respiratory disturbance, although post- operative machinery tests and laboratory surveys had detected some impairment of pulmonary function, which gradually improved with lapse of time. In conclusion age of the patients, length of the time delayed for surgery, severity of the nerve injury and the operative choice are the determining factors of the final results. PMID- 2598749 TI - [Meniscus plasty of the discoid cartilage of the knee joint. Report of 32 cases]. AB - During the time period from 1982 to 1987, 32 patients, 17 females and 15 males, aging 14 to 47, had their lateral discoid menisci reshaped operatively into nearly normal configuration. Final results of the treatment were both subjectively and objectively satisfactory confirmed at the time of re examinations, 3 to 48 months (25 pts. had been over one year) after operation. Reshaping the discoid meniscus not only brought about normal pattern of it, got rid of symptoms and signs caused by the discoid meniscus-itself, but also by eliminating the horizontal shearing force produced by non-physiological motion of the discoid meniscus, reasonably prevent, at least delay the development of osteoarthritis of that joint. PMID- 2598750 TI - Cyclosporine and inflammatory bowel disease. PMID- 2598751 TI - Irritable bowel syndrome in the gynecological clinic. Survey of 798 new referrals. AB - A study of the prevalence of symptoms suggestive of irritable bowel syndrome in 798 women referred to a gynecological clinic is reported; 321 women referred to dermatology and ear, nose, and throat clinics served as controls. Data were collected by a mailed symptom questionnaire. The prevalence of irritable bowel syndrome in the gynecological group was 37.3% compared with 27.7% in controls (P = 0.003). Approximately 50% of women referred with abdominal pain, dyspareunia, and dysmenorrhea had symptoms compatible with irritable bowel syndrome (P less than 0.005), whereas the prevalence in those referred for cervical abnormalities, termination/sterilization or perineal problems was similar to that of controls (28%). Patients referred with urinary symptoms, heavy periods, nonmenstrual bleeding, vaginal discharge, and infertility had an intermediate prevalence of irritable bowel syndrome (35-45%). This study suggests that either many women with irritable bowel syndrome are being wrongly referred to gynecologists or raises the possibility that symptoms currently regarded as indicative of irritable bowel syndrome may be associated with certain gynecological disorders. PMID- 2598752 TI - A meta-analysis of the role of smoking in inflammatory bowel disease. AB - A relationship between not smoking and ulcerative colitis has been examined in all English reports. This paper evaluates the ulcerative colitis/nonsmoking and the Crohn's disease/smoking association by meta-analysis and against causality criterion for chronic diseases. A review of the literature, meta-analysis of selected studies, and assessment of causality criterion all suggest that not smoking and ulcerative colitis and smoking and Crohn's disease are consistent with a causal relationship. It is not inconceivable that tobacco may contain some substance beneficial to ulcerative colitis patients. Identification of the specific product in tobacco producing a beneficial effect would be a prudent next step in the study of this association. In spite of the findings of this review and analysis, the author finds no justification for health care providers to change the Surgeon General's recommendations on smoking or tobacco use for ulcerative colitis patients specifically. PMID- 2598753 TI - Effect of antacid treatment on endogenous prostaglandin synthesis in human antral and duodenal mucosa. AB - Using 14C-labeled arachidonic acid as precursor for in vitro prostaglandin synthesis, the effect of an antacid containing Al (OH)3, Mg(OH)2 and CaCO3 on endogenous prostaglandin synthesis was investigated in antral and duodenal mucosa of healthy volunteers. After three weeks of treatment with a high-dose antacid, there was no detectable change in the total capacity of the mucosa for prostaglandin synthesis, but the prostaglandin profile was markedly altered. The relative amounts of PGE2 and PGF2 alpha synthesized by antral and duodenal mucosa increased at the expense of the prostaglandins A2/B2, thromboxane A2, and prostacyclin. In a short-term study, this change was not observed following a single antacid dose within 1 hr after application. It is concluded that long-term antacid treatment may alter the prostaglandin pattern formed by gastroduodenal mucosa and this may be related to its therapeutic effect. PMID- 2598754 TI - Protection of gastric mucosa against hypertonic sodium chloride by 16,16-dimethyl prostaglandin E2 or sodium thiosulfate in the rat: evidence for decreased mucosal penetration of damaging agent. AB - Protection of the gastric mucosa may be the result of either increased cellular resistance to injury (cytoprotection) or, alternatively, decreased exposure of mucosal cells to the damaging agent. To determine whether decreased exposure of mucosal cells to damaging agents plays a role in mucosal protection by 16,16-dm PGE2 or sodium thiosulfate, we estimated the intramucosal concentration of 22NaCl and measured its absorption from the gastric lumen into the systemic circulation 1 and 5 min after intragastric administration of hypertonic (25% w/v) 22NaCl. In an attempt to explain the differences observed, we also measured the net transmucosal water flux in control animals and rats pretreated with the protective agents. Administration of hypertonic NaCl rapidly (within 1 min) induced extensive hemorrhagic mucosal lesions that were significantly reduced by pretreatment with 16,16-dm PGE2 or sodium thiosulfate. Ultra-low temperature autoradiography indicated that luminal hypertonic 22NaCl penetrates the upper layers of the mucosa in relatively high concentrations (12.5% w/v) within 1 min but its concentration decreases rapidly and reached low levels (3.12% w/v) by 5 min. Absorption of NaCl from the gastric lumen into the systemic circulation 1 and 5 min after hypertonic NaCl was lower in both pretreatment groups than in the control. Net gastric transmucosal water flux (from serosa to mucosa) increased (P less than 0.05) from 100 +/- 2 in controls, to 1470 +/- 8 and 715 +/- 9 microliters in rats pretreated with 16,16-dm PGE2 and sodium thiosulfate, respectively. We conclude that 16,16-dm PGE2 and sodium thiosulfate protect the gastric mucosa against hypertonic NaCl, diminish mucosal penetration of NaCl, decrease mucosal absorption of NaCl, and significantly increase serosal to mucosal transmucosal water flux.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598755 TI - Characteristics of postprandial duodenal motor patterns in dogs. AB - In this study special attention was paid to the characteristics of duodenal motility under the influence of various test meals. Closely spaced strain gauge transducers and a computerized method were used to analyze motor patterns of the duodenum and the adjacent jejunum. Compared with an acaloric meal, nutrients shortened the length of contraction spread in the duodenum from 5.2 +/- 1.0 to 3.8 +/- 0.5-2.8 +/- 0.6 cm and in the jejunum from 10.5 +/- 3.0 to 7.4 +/- 1.3 5.2 +/- 0.8 cm. Additionally, contraction frequency was reduced. Basic differences were found between duodenal and jejunal motility. They were most marked in absence of nutrients. The duodenal motor pattern was characterized by a lower contraction frequency (8.0 +/- 2.2 vs 11.1 +/- 1.8/min), a shorter length of contraction spread (5.2 +/- 1.0 vs 10.5 +/- 3.0 cm), and a higher incidence of stationary contractions (50% vs 34%). On the duodenal bulb 72% of contractions represented contraction waves, whereas in the mid-duodenum the predominant feature was stationary contractions (57%) promoting the mixing of chyme with secretions. The characteristic duodenal motor patterns might be related to special functions of the duodenum for transport and digestion. PMID- 2598756 TI - Acid gastroesophageal reflux and symptom occurrence. Analysis of some factors influencing their association. AB - In 17 patients with esophagitis (degree I = erythema, N = 10; degree II = erosions, N = 7) esophageal pH was measured at 5 and 10 cm above the esophagogastric junction to assess whether the extension of acid reflux and the severity of the mucosal lesions could influence the association between reflux and symptoms. A minority of the refluxes were related with symptoms (4.0% and 7.7% in degree I, 14.1% and 12.0% in degree II at 5 and 10 cm respectively), whereas 65.4% and 100% of the symptoms were related with reflux in degrees I and II, respectively, with 76.5% and 35.7% occurring during refluxes reaching the proximal recording site. A relationship of symptoms with reflux is shown, particularly in erosive disease. Some reflux characteristics (extension, duration, acidity) seem to influence symptom occurrence mainly in mild esophagitis; however, more than 85% of the acid reflux episodes are symptom-free, regardless of the severity of the mucosal injury. PMID- 2598757 TI - Evaluation of gastroesophageal reflux as a cause of idiopathic hoarseness. AB - Eleven patients presenting to an ear, nose, and throat specialist were diagnosed as having idiopathic hoarseness and prospectively evaluated for evidence of gastroesophageal reflux (GER) to determine if an association existed. Testing for GER included voice analysis, EGD, esophageal manometry, Bernstein test, and ambulatory 24-hr pH monitoring. Six of the 11 (55%) hoarse patients studied had GER by pH monitoring (mean score 105 +/- 23), and most reflux episodes were supine and prolonged (20.9 +/- 8.2% supine pH less than 4.0, longest 129 min). All patients with abnormal pH monitoring had endoscopic esophagitis (Barrett's esophagus in two, peptic stricture in one, and erosive esophagitis in three), while none of the patients with normal scores had esophagitis. Symptoms of throat pain or nocturnal heartburn were more common in the GER-positive patients (6 of 6 vs 1 of 5), and clinically helpful in discriminating which hoarse patients had pathologic GER. Treatment with ranitidine 150 mg per os twice a day for 12 weeks improved esophagitis in all patients, but the voice improved in only one of the two patients with completely healed esophagitis. This study suggests that (1) GER is frequently seen in patients with idiopathic hoarseness (55%), (2) hoarse patients with throat pain or nocturnal heartburn are likely to have severe esophagitis and should be evaluated by EGD, and (3) additional antireflux and voice therapy may be necessary to heal esophagitis and improve the voice. PMID- 2598759 TI - Zollinger-Ellison syndrome in a patient with normal screening gastrin level. AB - A 59-year-old female presented with multifocal peptic ulcer disease and diarrhea. A fasting serum gastrin level obtained while the patient was receiving no antacid therapy was normal. A secretin stimulation test was positive. A small gastrinoma was found in the anterior duodenal wall at exploratory laparotomy. Normal fasting gastrin levels do occur in patients with overt Zollinger-Ellison syndrome and should not deter further investigation if clinical suspicion of this syndrome is high. PMID- 2598758 TI - Effect of antiandrogen flutamide on measures of hepatic regeneration in rats. AB - Male rat liver undergoes a process of demasculinization during hepatic regeneration following partial hepatectomy. The possibility that antiandrogens might potentiate this demasculinization process and in so doing augment the hepatic regenerative response was investigated. Adult male Wistar rats were treated with the antiandrogen flutamide (2 mg/rat/day or 5 mg/rat/day subcutaneously) or vehicle for three days prior to and daily after a 70% partial hepatectomy. At various times after hepatectomy, the liver remnants were removed and weighed. Rates of DNA and polyamine synthesis were assessed by measuring thymidine kinase and ornithine decarboxylase activities, respectively. Hepatic estrogen receptor status and the activity of alcohol dehydrogenase, an androgen sensitive protein, were measured. Prior to surgery, the administration of 5 mg/day flutamide reduced the hepatic cytosolic androgen receptor activity by 98% and hepatic cytosolic estrogen receptor content by 92% compared to that present in vehicle-treated controls. After hepatectomy, however, all differences in sex hormone receptor activity between the treatment groups were abolished. The rate of liver growth after partial hepatectomy in the three groups was identical. Moreover, hepatectomy-induced increases in ornithine decarboxylase activity and thymidine kinase activity were comparable. These data demonstrate that, although flutamide administration initially alters the sex hormone receptor status of the liver, these affects have no effect on the hepatic regenerative response following a partial hepatectomy. PMID- 2598760 TI - Budd-Chiari syndrome and Crohn's disease. An unreported association. AB - Hepatic vein thrombosis (Budd-Chiari syndrome) is a rare complication of ulcerative colitis and has not previously been reported in association with Crohn's disease. We here report the first known case of Crohn's disease presenting as the Budd-Chiari syndrome. PMID- 2598761 TI - Idiopathic recurrent pancreatitis from bile reflux? PMID- 2598762 TI - Sucrase activity in rat small intestine. PMID- 2598763 TI - Advances in bile acid therapy. Proceedings of the Second International Ursodeoxycholic Acid Symposium. Vail, Colorado, August 26 and 27, 1988. PMID- 2598764 TI - Bile acid-lipoprotein interactions: effects of ursodeoxycholic acid (ursodiol). AB - Several studies in the hamster model were undertaken to investigate known and recently disclosed metabolic interactions between bile acids and lipoproteins, particularly between ursodiol and low-density-lipoprotein (LDL) receptors. Three groups of animals, receiving a control 0.027% cholesterol diet, supplementation with 0.1% ursodiol, or supplementation with 0.1% chenodeoxycholic acid, were treated for four weeks. Both bile acids suppressed bile acid synthesis. Chenodeoxycholic acid significantly increased serum total cholesterol compared to ursodiol, and high-density-lipoprotein (HDL) cholesterol decreased significantly with chenodeoxycholic acid compared to ursodiol and control. Since the rate of bile acid synthesis is known to influence LDL receptor activity, LDL uptake under these conditions of synthesis suppression was measured. The animals received infusions of hamster LDL and methylated human LDL. Uptake of hamster LDL (occurring by both receptor-dependent and receptor-independent mechanisms) was significantly higher in the ursodiol-treated group than in the others. Human LDL uptake (occurring only by receptor-independent mechanisms) was not significantly affected by either treatment. The mechanisms by which ursodiol apparently directly stimulates the LDL receptor remain speculative but may involve alteration of cell membrane fluidity, change in the rate of LDL receptor cycling, and increase in the number of LDL receptors. PMID- 2598765 TI - Structure-activity relationship studies on natural and synthetic bile acid analogs. AB - The objective of our research was to develop ursodiol analogs that are structurally modified to modulate hepatic side-chain amidation and prevent 7 dehydroxylation by intestinal bacteria while at the same time maintaining the critical micellar concentration (CMC) and hydrophilicity of ursodiol. More than 20 naturally occurring bile acids were screened for physicochemical properties. Then, two generations of analogs were studied, and those with physicochemical properties similar to ursodiol's were analyzed for physiologic properties. The first generation of analogs included molecules with steric and/or electronic hindrance on the side chain; the second group consisted of the same molecules conjugated with glycine or taurine and also "pseudoconjugated" analogs (23 hydroxylated, esterified, and amidated with other amino acids). Of the first generation analogs, only cyclopropane D derivative and trans-olefin were useful to our purposes, being conjugated by the liver and almost completely recovered in bile. These two analogs were deconjugated and 7-dehydroxylated but with slower kinetics. The hydrophilicity of the molecules could be augmented by increasing the polarity of the steroid ring. Among the pseudoconjugated analogs, the CMC values were similar to those of the natural analogs, although hydrophobicity differed among the group. The analogs that were not deconjugated were not 7 dehydroxylated either. All of the pseudoconjugated bile acids were efficiently taken up by the liver, and their recovery in bile was similar to that of glycine and taurine ursodiol. From these studies we now know that side chain configuration and conformation are important in the conjugation and deconjugation processes. Mild modification of the side chain can prevent 7-dehydroxylation and thus yield a bile acid more resistant to intestinal bacteria and more bioavailable. Prevention of hepatic conjugation improves biliary secretion and recovery of many analogs. PMID- 2598766 TI - Gallstone dissolution therapy with ursodiol. Patient selection. AB - Ursodeoxycholic acid (ursodiol) has been shown to be an effective oral agent for dissolution of gallstones that also has a favorable safety profile. In the selection of patients as candidates for this treatment, stone characteristics and the functional status of the gallbladder are the two most important criteria. Small, primarily cholesterol stones (radiolucent on plain film) are the most suitable for oral dissolution therapy. In addition, a functioning gallbladder (as evidenced by visualization on oral cholecystogram) is required to concentrate the ursodiol-enriched bile and effect stone dissolution. Ursodiol should not be used during pregnancy, in women likely to become pregnant, or in severe acute or chronic intrahepatic cholestasis. Acute cholestasis and common bile duct obstruction also preclude this treatment. Screening tests include basic laboratory tests of liver function, sonographic evaluation of the gallbladder and biliary tree, plain film of the abdomen, and oral cholecystogram. Since few patients meet all the selection criteria ideally, the decision to undertake treatment with ursodiol must be based on the entire clinical profile and on the patient's willingness to accept the predicted likelihood of success. PMID- 2598767 TI - Postdissolution gallstone recurrence. A clinical perspective. AB - The intuitive assumption that gallstones will rapidly recur in all patients is clearly incorrect. At least 50% of patients do not develop stones within three to five years of complete dissolution, and the risk may decrease after the first two or three years. This is not so surprising when one considers the complexity of the pathogenic process. Bile must be sufficiently supersaturated with cholesterol, an imbalance in nucleating and antinucleating factors must occur, at least transiently, and, for some patients, a defect in gallbladder emptying may be necessary. Occasionally, pathogenic mechanisms that had been present, eg, estrogens, obesity, or medications such as clofibrate, may no longer be active. The best method to reduce the risk of recurrence is to reverse one or more of the essential pathogenic mechanisms. Desaturating bile in cholesterol by oral therapy with a bile acid such as ursodiol should be effective. A search for other safe, effective, and cost-effective approaches persists, eg, for novel bile acids resistant to bacterial degradation and for various dietary regimens. Alteration of cholesterol nucleation with nonsteroidal antiinflammatory agents is also under investigation. In addition, enhancement of gallbladder emptying is an interesting approach that is worth studying. If stones do recur, the course of action is not always clear. Recurrent stones are usually "silent," and we do not usually treat asymptomatic stones. These small cholesterol stones are temptingly easy to dissolve, however. At least in those patients whose level of surgical risk would be high if symptoms developed, prophylactic dissolution therapy may be desirable. PMID- 2598768 TI - Effect of ursodeoxycholic acid administration on biliary lipid secretion in primary biliary cirrhosis. AB - Ursodeoxycholic acid (UDCA) has been reported to improve liver function tests when administered to patients with cholestatic liver diseases, such as primary biliary cirrhosis (PBC). However, its effects on biliary lipid metabolism in patients with PBC are still unknown. In this study we report the effect that UDCA (600 mg/day, for four weeks) had on biliary cholesterol saturation index, biliary bile acid pattern and pool size, and biliary lipid output in seven female patients (ages 34-58 years) with PBC, stages I to III. A significant improvement of liver function tests was observed after four weeks of treatment. Saturation index was significantly decreased from 1.23 +/- 0.1 to 0.7 +/- 0.08 (P less than 0.02); this effect was due to the significant decrease of biliary cholesterol concentration from 6.7 +/- 0.36 to 3.6 +/- 0.37 percent molar (P less than 0.02). A significant decrease of cholesterol output (from 88 +/- 9 to 55 +/- 10 mumol/hr, P less than 0.02) was also observed. The amount of cholic acid, the predominant bile acid in bile, significantly decreased (from 47.3 +/- 3.5 to 35.4 +/- 2.6 percent molar, P less than 0.02), as did amounts of chenodeoxycholic and deoxycholic acids, while the amount of UDCA rose from 1.6 +/- 1.0 to 34.0 +/- 1.3 percent molar (P less than 0.02). Total bile acid pool size was not affected by UDCA, but the evaluation of individual bile acid pool sizes showed an increased proportion of UDCA relative to the endogenous bile acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598769 TI - Effect of different doses of ursodeoxycholic acid in chronic liver disease. AB - Recent clinical studies have indicated that ursodeoxycholic acid (ursodiol), administered at dosages ranging between 10 and 15 mg/kg/day, improves liver function indices in both cholestatic and inflammatory chronic liver diseases. These dosages would be considered high for the use of ursodiol in gallstone dissolution therapy. To investigate the dose-response relationship to ursodiol administration, we planned a few studies in patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and chronic hepatitis (CH). Patients with PBC were subdivided into two groups on the basis of their serum bilirubin values, with 2 mg/dl as the dividing line. Ursodiol was given at dosages of 250, 500, and 750 mg/day for consecutive periods of two months, the order of treatment being randomly assigned to each patient. The enrichment with ursodiol of biliary bile acids was similar in both PBC and CH and, within the PBC group, in both anicteric and icteric patients. Highly significant decreases in serum enzyme levels were observed in all groups with the 250 mg/day dose, corresponding to about 4-5 mg/kg/day. The two higher doses induced further improvements in serum enzyme levels, especially in patients with PBC, but no significant differences were found between the 500 and the 750 mg/day doses. The improvements were roughly proportional to the enrichment of conjugated biliary bile acids with ursodiol. Serum bilirubin levels, an important prognostic factor in PBC, were also significantly reduced by ursodiol administration in patients with initial serum levels higher than 2 mg/dl. The present study indicated that ursodiol is a potentially useful drug for chronic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598770 TI - cDNA sequence, gene organization, and progesterone induction of mRNA for uteroferrin, a porcine uterine iron transport protein. AB - The complete nucleotide sequence of porcine uteroferrin mRNA was determined by analysis of overlapping cDNA and genomic clones. The uteroferrin mRNA is 1,424 nucleotides in length and encodes a precursor protein of 338 amino acids, of which 20 residues subsequently are cleaved to form the mature peptide. The uteroferrin gene spans 3.5 kb and consists of three exons and two introns. The first intron separates the 5' untranslated sequences from the translation initiation codon ATG while the other intron interrupts the coding region of the mature protein. Primer extension analysis localized the presumptive transcription initiation site of the mRNA 94 nucleotides 5' of the ATG. No canonical TATA or CAAT sequences were apparent upstream from the mRNA cap site. However, sequences within the 5'-flanking region of the gene exhibit similarities to defined regulatory sequences for iron- and steroid hormone-responsive genes. The steady state level of uteroferrin mRNA is enhanced by progesterone but not by estrogen alone, although the extent of progesterone induction is lower than at midgestation. The simple organization of the uteroferrin gene, which contrasts with those of the transferrin gene family, and the progesterone induction of uteroferrin mRNA expression suggest that, although this protein may have evolved in a manner distinct from other iron binding proteins, its regulation by steroid hormones may be similar. PMID- 2598771 TI - The cDNA structure of rat plasma kallikrein. AB - From a liver cDNA library we have isolated and characterized the cDNA encoding rat plasma kallikrein. The cDNA structure contains 2,456 nucleotides with a 2,082 nucleotide-long open reading frame. Protein sequence data suggest that the signal peptide is 19 amino acids long. This results in a mature plasma prekallikrein containing 619 amino acids. Determination of tissue distributions using Northern blot analysis (3.0-kb transcript) and the polymerase chain-reaction methodology on RNA preparations demonstrated that in the rat the liver is the main source of this enzyme. Southern blots suggested the presence of a single gene coding for rat plasma kallikrein. Finally, although Southern blots revealed a homologous gene in mouse, the mRNA corresponding to the mouse hepatic proteinase is barely detectable on Northern blots, suggesting inefficient transcription or high turnover of the mRNA in this species. PMID- 2598773 TI - [Specific properties of DNA from fractions of isolated mouse synaptonemal complexes]. PMID- 2598772 TI - [Primary structure of atypical influenza A(H3N2) viruses 1982-1986]. PMID- 2598774 TI - [Dependence of the amplitude of kinesthetic evoked potentials on the rate and acceleration of hand movement in monkeys]. PMID- 2598775 TI - In vivo activity and metabolic fate of 2-(2,3,3-triiodoallyl)tetrazole (ME1401), a novel antifungal agent. AB - 2-(2,3,3-Triiodoallyl)tetrazole (ME1401), a novel antifungal agent, showed therapeutic effectiveness in topical treatment of experimental dermal infections with Trichophyton mentagrophytes and Candida albicans in guinea-pigs. Addition of diethyl sebacate to the ME1401 preparations increased its in vivo antifungal activity and its penetration into the skin. When the estimation of efficacy of treatment with active formulations was made on the basis of skin lesion and the rate of negative skin cultures in comparison with those for infected, untreated or placebo-treated controls, the in vivo activity of 0.5% ethanol tincture or gel of ME1401 was comparable to that of reference antimycotic drugs such as clotrimazole, haloprogin and others. Pharmacokinetic studies in the experimental animals demonstrated that ME1401 was unstable in vivo, being readily converted to an active metabolite 2-(3-iodopropargyl)tetrazole (CN144) first and then to 2 propargyltetrazole (CN151). CN144 showed potent in vitro and in vivo antifungal activities, while the in vitro activity of CN151 was negligible. PMID- 2598776 TI - Antibacterial activity of norfloxacin against 1700 relatively resistant clinical isolates. AB - A total of 1724 clinical isolates from patients with different infections were tested in vitro to determine their susceptibility to norfloxacin. Antibacterial activity of norfloxacin was compared with other drugs that were commonly used in the hospital. Of the 919 strains of Enterobacteriaceae tested, all except four isolates of Enterobacter, two of Serratia and one of Proteus were susceptible to norfloxacin. Ninety-five percent of the 199 strains of Pseudomonas aeruginosa were also inhibited by this quinolone. Brucella melitensis (81 strains) was completely susceptible to norfloxacin. All the 250 isolates of Staphylococcus aureus and coagulase-negative staphylococci were also sensitive to norfloxacin. Pseudomonads other than P.aeruginosa, Acinetobacter/Alcaligenes and group D streptococci were less sensitive to norfloxacin, with 56%, 57% and 20% respectively being inhibited by this antimicrobial agent. PMID- 2598777 TI - Experimental studies on antirheumatic crude drugs used in Saudi traditional medicine. AB - A large number of herbal drugs are used in the traditional medicine of Saudi Arabia for the treatment of rheumatism, arthritis, gout and other forms of inflammation. In the present study seven of these crude drugs, namely Francoeuria crispa, Hammada elegans, Malus pumila, Ruta chalepensis, Smilax sarsaparilla, Achillea fragrantissima and Alpinia officinarum were tested against carrageenan induced acute inflammation in rats. The plant materials were extracted with 96% ethanol. The dried extract was dissolved in water for pharmacological testing. The rats were administered an oral dose of 500 mg/kg body weight of each extract 1 h prior to production of inflammation by carrageenan injection (0.05 ml of 1% carrageenan suspension in the planter aponeurosis of the right hind foot). The paw volume was measured at 0,2,3 and 4 h after the injection. Four of the seven plants, namely Francoeuria crispa (24%), Malus pumila (23%), Ruta chalepensis (30%) and Smilax sarsaparilla (25%), produced significant inhibition of carrageenan-induced inflammation in rats. These plants also inhibited cotton pellet-induced exudation. Further studies are suggested to isolate the active principles and for the determination of the mechanism of action of these drugs. PMID- 2598778 TI - [Dynamic changes of the plasma prekallikrein activity in patients with acute myocardial infarction]. AB - The activity of the plasma prekallikrein was assayed by using dextran sulfate as activator and chromogenic compound substance Na-benzoyl-DL-arginine-4-nitroanilid hydrochloride (BAPNA) as substrate. The dynamic changes of the plasma prekallikrein activity were observed in 22 patients with acute myocardial infarction (AMI) at different period. The correlation between plasma prekallikrein activity and serum CPK activity were analysed in part of the patients. The results indicate that the plasma prekallikrein activity decreased significantly in AMI, especially on the third day after onset. The decrease of plasma prekallikrein and increase of serum CPK were correlated negatively. The results indicate that the chromogenic compound substance BAPNA can be used to determine the activity of plasma prekallikrein. The kinin system was activated by certain factors in AMI, causing the decrease of plasma prekallikrein and increase of bradykinin. PMID- 2598779 TI - [Electrophysiologic effects of intravenous propafenone]. AB - The electrophysiological effects of intravenous propafenone were studied with programmed electrical stimulation in 31 patients. Among them 29 cases with SVT (including WPW syndrome in 11, paroxysmal AF or Af in 3) and the other two cases were studied for other reasons. The results showed that: (1) Propafenone has significant effects on each part of the special conduction tissues of the heart as well as the accessory pathway. (2) It is an effective drug for treating AVNRT and the tachycardias associated with WPW syndrome. (3) There were no effects on sinus node function in all except one patient whose SNRT was prolonged to 2020 ms. (4) Neither blood pressure dropping nor other side effects were found during the studies. PMID- 2598780 TI - [Free calcium in platelets and the serum in essential hypertension]. AB - Intracellular free calcium of platelets was studied in 45 patients with essential hypertension and in 6 patient's normotensive offspring. Intracellular free calcium of platelets in hypertensive patients was significantly higher than those in normotensive subjects (223 +/- 26 vs 170 +/- 28 nmol/lL, P less than 0.001). There was a positive correlation between intracellular free calcium of platelets and blood pressure (r = 0.653 approximately 0.729, P less than 0.001). No increase of intracellular free calcium of platelets was found in patient's normotensive offspring. 33 patients also had serum free calcium measured simultaneously. There was no difference between patients and the normotensive control (1.10 +/- 0.15 vs 1.09 +/- 0.10 mmol/L, P greater than 0.05). However, a positive correlation between serum free calcium and blood pressure (r = 0.363, P less than 0.05) and a weak positive correlation between serum free calcium and intracellular free calcium of platelets (r = 0.337, r 0.05 = 0.344) were found. These results indicated that intracellular free calcium was involved in the regulation of blood pressure, it was postulated that the intracellular free calcium of smooth muscle cell in the peripheral arteriole with resistance might have the similar changes seen in platelets. The changes of intracellular free calcium of platelets might be valuable in the prevention and treatment of hypertension and its vascular complications. PMID- 2598781 TI - [Hemodynamic effects of isoprenaline, dopamine, atrial and ventricular pacing during the early period after correction of tetralogy of Fallot]. AB - The hemodynamic changes in 12 children (mean age 6 years) with Tetralogy of Fallot (TOF) were studied during the first 24 hours after surgical correction. The effects of isoprenaline and dopamine were compared. 7 of them using atrial and ventricular pacing also have their effects compared. The results show that patients with small left ventricles generally suffer low cardiac output or a trend to low cardiac output. The chronotropic drug (isoprenaline) was more effective than inotropic drug (dopamine) in increasing CI due to its ability in increasing HR and decreasing SVR. Atrial pacing was an effective method in increasing CI if the atrioventricular conduction is normal, while ventricular pacing did not increase CI at all. PMID- 2598782 TI - [Localization of the origin of ventricular arrhythmia by means of Frank's vectorcardiogram]. AB - Frank's lead system vectorcardiogram (VCG) was used to record the ventricular arrhythmias (VA) of different areas induced by pacing in 22 canines and by stimulating the epicardium of different areas in 8 patients of mitral stenosis during operation. The results showed that VCG can localize the origin of VA of 13 areas in canines and 9 areas in human. To localize the VA at or near ventricular septum VCG is more accurate than ECG (94% vs 70%). PMID- 2598783 TI - [Electrophysiologic study of ventricular tachycardia and drug tests]. PMID- 2598784 TI - [A study of intracardiac blood flow rate by Doppler echocardiogram in healthy Chinese adults of various ages]. PMID- 2598785 TI - [Relation of ECG and left ventricular parameters in hypertensive patients]. PMID- 2598786 TI - [Risk factors and prognosis of ventricular arrhythmia during heart failure]. PMID- 2598787 TI - [Clinical uses of external noninvasive temporary pacing]. PMID- 2598788 TI - [Calcitonin gene-related peptide in normotensive and spontaneously hypertensive rats]. AB - Using specific radioimmunoassay, radioimmunoreceptor analysis and gel filtration, we found that calcitonin gene-related peptides (CGRP) were distributed in various tissues of normotensive rat (WKY) and spontaneously hypertensive rat (SHR), the highest content was in the lumbar spinal cord (1197 +/- 94.8 pg/mg tissue), the lowest in the auricle (15.0 +/- 2.1 pg/mg tissue). Compared with WKY, the plasma CGRP concentration decreased and the CGRP content in abdominal aorta and hypothalamus increased in SHR. By gel filtration, it showed that only one major molecular form of CGRP was present in the tissues. The CGRP specific binding sites were present both in SHR and WKY hearts, but the number of CGRP binding sites in SHR heart was higher and the binding affinity lower than those in WKY heart. Besides, CGRP can reduce the mean arterial pressure (MAP) in the SHR in a dose-dependent way. The above data indicated that CGRP may play an important role in the pathogenesis of hypertension and exert possibly a therapeutic effect on hypertension. PMID- 2598789 TI - [A deliberation on the anticholesterol effect of oats]. PMID- 2598790 TI - [Clinical and serological characterization of Chlamydia-induced arthritis]. AB - Chlamydia-induced arthritis was diagnosed in 32 patients (18 men and 14 women; mean age 33 [17-54] years). 13 were HLA-B27 positive. In 19 patients the arthritis was largely confined to one joint. Enthesopathies occurred in 14 patients, and in 13 sacroiliitis was diagnosed radiologically. The most frequent extra-articular changes affected the urogenital system (26 cases). The full Reiter syndrome was present in seven patients (four men, three women). All patients had serum antibodies against Chlamydia. In 16 patients Chlamydia was diagnosed as the causative organism by urogenital swab. Chlamydia-induced arthritis differs from other arthritides in the high proportion of HLA-B27 negative patients. PMID- 2598792 TI - [Ischemic reaction in a young woman without coronary sclerosis: Bland-White Garland syndrome]. AB - A 39-year-old woman, with known mild mitral regurgitation, developed progressively more severe symptoms of angina, associated with an ischaemia response in the exercise electrocardiogram. Angiocardiography demonstrated an anomalous origin of the left coronary artery from the pulmonary artery (Bland White-Garland syndrome). At operation an aortocoronary venous bypass graft was constructed; the patient has been without symptoms since and the exercise ECG is normal. As demonstrated by angiography, the previously marked dilatation of the right coronary artery had largely regressed and previously present collaterals to the left coronary artery were no longer visualized three months after operation. The described coronary artery anomaly, although rare, should be considered in a young patient with reproducible coronary artery ischaemia. PMID- 2598791 TI - [3 beta-hydroxysteroid dehydrogenase deficiency and 21-hydroxylase deficiency in hirsutism]. AB - Of 218 women with hirsutism 16 (7%) were found to have partial 21-hydroxylase deficiency, while 38 (17%) had partial 3 beta-hydroxysteroid dehydrogenase deficiency. Six women (3%) had a steroid constellation which resembled that of an augmented adrenarche. In the women with enzyme deficiency over-weight and abnormal menstruations were more frequent (50%) than in those without such deficiency (33%). The degree of hirsutism and age at diagnosis were similar in those with and those without partial enzyme deficiency. Furthermore, the diagnosis of partial enzyme deficiency could only be made with certainty by the ACTH stimulation test, because with sole measurement of basal levels (17 hydroxyprogesterone and 21-desoxycortisol in 21-hydroxylase deficiency, and 17 hydroxypregnenolone and dehydroepiandrosterone in 3 beta-hydroxysteroid dehydrogenase deficiency) the enzyme defects are in most instances not revealed. PMID- 2598794 TI - [Early defibrillation in the emergency doctor rendezvous system]. PMID- 2598793 TI - [Bilateral gallbladder rupture after blunt abdominal trauma]. AB - A 65-year-old man under the influence of alcohol sustained blunt trauma to the abdomen in an accident while riding a motorcycle. An intramural haematoma of the gall-bladder was demonstrated by computed tomography: peritoneal lavage was negative. About five hours later the gall-bladder ruptured, as confirmed at laparotomy. The postoperative course after cholecystectomy was uneventful. PMID- 2598795 TI - [Ectopic tissue as polypoid lesions of the gallbladder]. PMID- 2598796 TI - [Urine glucose testing in children with diabetes mellitus--obsolete as a daily control measure?]. AB - Sixty-four children with type 1 diabetes (33 girls and 31 boys with a mean age of 11 1/4 years) were studied in order to ascertain whether urine sugar measurements performed by the patients or their parents can provide adequate monitoring of treatment. The results of two home-testing methods for urine glucose were compared with subsequent glucose dehydrogenase assays in the laboratory. Over the range from 0 to 5 g/dl the results of home testing disagreed with the laboratory checks by an average of one concentration grade, and displayed wide scatter. Only in the concentration range of 0.5 g/dl were there differences between the nonspecific reduction test (Clinitest) and the specific enzymatic assay. Glucose concentrations in urine specimens passed at 7 am, 12 noon and 6 pm (home testing) were compared with blood glucose concentrations checked at the same times. Correlation was not very close (correlation coefficients between 0.3 and 0.64). Correlation between pooled urine collections and 24 hour blood sugar profiles was equally poor (0.5-0.6). The author concludes that urine sugar testing is unsatisfactory for home monitoring of children with diabetes and the results are inadequate for diagnostic or therapeutic purposes. PMID- 2598797 TI - [Minitracheotomy. A new, simple method of treatment for postoperative sputum retention]. PMID- 2598798 TI - [Causes of and treatment possibilities for generalized lipomatosis]. PMID- 2598800 TI - [Thoracic actinomycosis]. PMID- 2598799 TI - [Fibrin glue]. PMID- 2598801 TI - [Udder health control of dairy cows in the area of Ankara (Turkey)]. AB - The udder health of dairy cows is necessary in order to serve the consumer with milk and milk products of perfect quality and sound hygiene. Also in districts where the dairy industry is less developed a better udder health can be obtained when certain hygiene rules are carried out in connection with simple diagnostic and therapeutic measurements. PMID- 2598802 TI - [The helminth fauna of the gastrointestinal tract of young cattle in northwest Germany]. AB - Ten unmedicated animals of a controlled anthelmintic trial were used to analyse the present gastrointestinal helminth fauna of young cattle from the northwest of Germany. This survey done in August revealed Ostertagia ostertagi to represent the most prevalent and abundant species followed by Cooperia oncophora and Nematodirus helvetianus. O. lyrata, O. leptospicularis, C. zurnabada, C. punctata, Trichostrongylus axei, Haemonchus contortus, Bunostomum phlebotomum, Capillaria bovis and Trichuris discolor were less prevalent and abundant. These findings are closely similar to findings from investigations more than 20 years ago although since that time anthelmintics have been used increasingly. PMID- 2598803 TI - [Safety precautions during semen collections from stallions]. AB - In the Federal Republic of Germany a lethal accident occurred recently during the semen collection from a stallion and it would be advisable to observe the safety rules of which there are three sections: hobbeling and if necessary twitching of the mare, security in the manner in which the stallion is led, precautions to be observed by the operator. PMID- 2598805 TI - Bacterial infertility in camels (Camelus dromedarius): isolation of Campylobacter fetus. AB - This study constitutes the first reported isolation of C. fetus subsp. venerealis from cervical swabs in breeding camels. 9 of 30 camels which were barren for a long period were found to be positive for C. fetus. The methods of isolation are described. Additionally, cervical flora of 30 camels were examined. 9 different bacterial species were isolated of which Staphylococcus aureus was most frequently found. All samples were negative for Trichomonas sp. and Streptococcus zooepidemicus. PMID- 2598804 TI - [Subclinical coccidiosis in broilers and pullets]. AB - In the period from 1985 to 1987, 24 broiler crops (12 houses; one integration and 3 farms) and 9 pullet flocks (9 houses, 4 farms) were examined for parasites. Intestinal lesion scores and the number of parasites in the intestinal lumen (semiquantitative estimation) were recorded, and the Eimeria species determined when possible (broilers crops: 3rd and 5th week, pullet flocks 4th, 8th, 12th and 18th week). Additionally, the quantity of parasites in litter or faecal samples was examined in regular intervals. Clues for economic damage were only found in broiler crops with increased numbers of coccidial oocysts per gram litter in the 5th week of the fattening period. Eimeria tenella and E. acervulina were the dominating species in broiler chickens and also pullets, E. maxima oocysts however were only casual findings. No ectoparasites, helminths or other protozoa than Eimeria were observed. With regard to the intestinal lesions and the quantities of parasites in the intestine no significant differences were seen when comparing selected broiler chicks and birds taken at random. In pullet flocks the examination of random samples was the superior method, because only freshly dead bodies, collected in insufficient numbers, were suitable for diagnostics. In 3 broiler crops and one flock of replacement pullets kept on a wired floor no Eimeria were diagnosed. PMID- 2598806 TI - [Microscopic studies of the skin of the Turkish Angora goat. I. Skin layers]. AB - The study describes basic structural aspects of the integumental layers (epidermis, dermis, hypodermis) of the Turkish Angora goat. The results have been obtained by light- and electronmicroscopical methods. Central topics are measurements of layer thickness as related to annual season and life period, as well as typical criteria of integumental layer construction as connected with the hair cycle. Remarkable is a trimerous organization of the dermis and cyclic changes in the thickness of the stratum adiposum of the hypodermis. The findings are discussed with regard to comparable observations from other domestic mammals. PMID- 2598807 TI - [Experiences with the testing of the microbial count in drinking water from two laying hen battery sheds]. AB - Samples of drinking water were taken from different sites of two laying hen battery cage barns at 10 days during four months. The result of the bacteriological investigation showed large differences. Up to 5000 CFU/ml were found in the water of the pressure supply vessel. Samples taken from the nipple drinkers even showed higher numbers. It seems that the heterogeneous results are not primarily caused by the methods used. It is assumed that there are still unknown factors present in the drinking water supply system of laying hen battery cage barns which influence the germ content in the drinking water. PMID- 2598808 TI - [A plea for comprehensive interpretation in microclimate areas]. AB - Microclimate is an important factor in modern intensive stockbreeding. At any rate, it ought to be judged in the context of other stress factors. Since microclimate is variable in the stable, it ought to be measured with the purpose of possibly effectuating a correction. The microclimate of a stable, which is also dependent on the outer climate situation, cannot always be improved solely by means of ventilation. However, the ventilation system should always be coordinated with the dung removal system of the stable. PMID- 2598809 TI - [Picture report: urethral fistula in a ram]. PMID- 2598810 TI - Region-specific deposition of dermal proteins between dermis and epidermis during induction of chick feather and scale rudiments. AB - To begin to study the role of particular proteins in inductive tissue interactions, we have used density labelling techniques to determine whether any dermal proteins are found between embryonic chick dermis and epidermis at a stage when the dermis plays an important inductive role in epidermal differentiation. Epidermis will form feathers or scales depending on whether it interacts with dorsal or foot dermis, respectively, and the dermis can still influence epidermal differentiation when direct cell contact between the tissues is blocked by a membrane filter during culturing (Peterson & Grainger, 1985). In transfilter experiments, we detect a subset of dermal proteins within the filter between the tissues. Several of these dermal proteins are deposited in a region-specific manner, that is, they are only found associated with filters from either dorsal or foot dermis. We have previously shown that the expression of some of these proteins is specific to particular regions of dermis and is also associated with the inductive potential of the dermis (Peterson & Grainger, 1986). We detect only 17 dermal proteins which are transferred across the filter in these cultures and found in direct association with epidermis; of these 14 are common to both dorsal and foot dermis, and 3 are deposited in a region-specific manner. Our results lead us to hypothesize a significant function for certain dermal proteins in this inductive interaction either as part of the extracellular matrix or in direct association with epidermis. PMID- 2598811 TI - An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo. AB - Embryonic stem cells (ES) cells were injected into host blastocysts either in groups of 10-15 cells or as single cells in order to test their developmental potential in the developing embryo. The analysis of midgestation chimaeras, by electrophoretic separation of glucose phosphate isomerase (GPI) isozymes, showed that ES cells were capable of colonizing trophectoderm and primitive endoderm derivatives at a low frequency, as well as producing a high rate of chimaerism in tissues of the fetus and extraembryonic mesoderm. PMID- 2598812 TI - Pattern formation in the Drosophila embryo: allocation of cells to parasegments by even-skipped and fushi tarazu. AB - The first sign of metamerization in the Drosophila embryo is the striped expression of pair-rule genes such as fushi tarazu (ftz) and even-skipped (eve). Here we describe, at cellular resolution, the development of ftz and eve protein stripes in staged Drosophila embryos. They appear gradually, during the syncytial blastoderm stage and soon become asymmetric, the anterior margins of the stripes being sharply demarcated while the posterior borders are undefined. By the beginning of germ band elongation, the eve and ftz stripes have narrowed and become very intense at their anterior margins. The development of these stripes in hairy-, runt-, eve-, ftz- and engrailed- embryos is illustrated. In eve- embryos, the ftz stripes remain symmetric and lack sharp borders. Our results support the hypothesis (Lawrence et al. Nature 328, 440-442, 1987) that individual cells are allocated to parasegments with respect to the anterior margins of the eve and ftz stripes. PMID- 2598813 TI - Ectodermal inhibition of cartilage differentiation in micromass culture of chick limb bud mesenchyme in relation to gene expression and cell shape. AB - Ectoderm inhibits the formation of cartilage by chick wing bud mesenchyme in micromass culture. This suggests that the pattern of cartilage formation in the limb bud may result from a restriction of cartilage cell differentiation to the limb bud core as cells leave the progress zone. We have used in situ hybridization to investigate whether ectodermal inhibition in micromass culture occurs at the level of gene transcription. We found that ectoderm completely inhibited the accumulation of cartilage-specific type II collagen transcripts in the mesenchyme cells, whilst the level of type I collagen transcripts was unaffected. Morphometric analysis of electron micrographs revealed that inhibition of chondrogenesis in micromass culture was not preceded by cell flattening. In fact, a rounded cell shape was found not to be a prerequisite for cartilage cell differentiation in micromass. PMID- 2598814 TI - Differential gene expression in the anterior neural plate during gastrulation of Xenopus laevis. AB - We have isolated three cDNA clones that are preferentially expressed in the cement gland of early Xenopus laevis embryos. These clones were used to study processes involved in the induction of this secretory organ. Results obtained show that the induction of this gland coincides with the process of neural induction. Genes specific for the cement gland are expressed very early in the anterior neural plate of stage-12 embryos. This suggests that the anteroposterior polarity of the neural plate is already established during gastrulation. At later stages of development, two of the three genes have secondary sites of expression. The expression of these genes can be induced in isolated animal caps by incubation in 10 mM-NH4Cl, a treatment that is known to induce cement glands. PMID- 2598815 TI - Tissue specific O-linked glycosylation of the neural cell adhesion molecule (N CAM). AB - We have shown previously that the predominant N-CAM isoform in skeletal muscle myotubes contains as a result of alternative splicing a novel domain (MSD1) in its extracellular region. Here we show that this region represents a site for O linked carbohydrate attachment. The lipid tailed N-CAM in myotubes was found to bind peanut lectin while the transmembrane isoform from myoblasts lacking MSD1 did not. In addition, N-CAM from a variety of neural sources failed to bind the lectin. Analysis of 3T3 fibroblasts transfected with various N-CAM cDNAs, showed that peanut lectin binding was correlated specifically with the expression of the MSD1 region. The oligosaccharides isolated from a purified preparation of myotube N-CAM were shown to contain an O-linked oligosaccharide whose core structure was a sialylated version of Gal beta 1----3GalNac which is the structure recognized specifically by peanut lectin. These data provide the first evidence for the expression of O-linked carbohydrate on any N-CAM isoform and more specifically target this oligosaccharide to the MSD1 region of myotube N-CAM. PMID- 2598816 TI - The specification of heart mesoderm occurs during gastrulation in Xenopus laevis. AB - The establishment of heart mesoderm during Xenopus development has been examined using an assay for heart differentiation in explants and explant combinations in culture. Previous studies using urodele embryos have shown that the heart mesoderm is induced by the prospective pharyngeal endoderm during neurula and postneurula stages. In this study, we find that the specification of heart mesoderm must begin well before the end of gastrulation in Xenopus embryos. Explants of prospective heart mesoderm isolated from mid- or late neurula stages were capable of heart formation in nearly 100% of cases, indicating that the specification of heart mesoderm is complete by midneurula stages. Moreover, inclusion of pharyngeal endoderm had no statistically significant effect upon either the frequency of heart formation or the timing of the initiation of heartbeat in explants of prospective heart mesoderm isolated after the end of gastrulation. When the superficial pharyngeal endoderm was removed at the beginning of gastrulation, experimental embryos formed hearts, as did explants of prospective heart mesoderm from such embryos. These results indicate that the inductive interactions responsible for the establishment of heart mesoderm occur prior to the end of gastrulation and do not require the participation of the superficial pharyngeal endoderm. PMID- 2598817 TI - Roles of neuroepithelial cell rearrangement and division in shaping of the avian neural plate. AB - Shaping of the neural plate, one of the most striking events of neurulation, involves rapid craniocaudal extension. In this study, we evaluated the roles of two processes in neural plate extension: neuroepithelial cell rearrangement and cell division. Quail epiblast plugs of constant size were grafted either just rostral to Hensen's node or paranodally and the resulting chimeras were examined at selected times postgrafting. By comparing the size of the original plug, the number of cells it contained and the distribution of cells within it to those same features of the grafts in chimeras, we were able to ascertain that, during transformation of the flat neural plate into the closed neural tube (a period requiring 24 h), the graft undergoes a maximum of 3 rounds of craniocaudal extension (each round of craniocaudal extension was defined as a doubling of graft length, so 3 rounds equaled an 8-fold increase in length). Such extension is accompanied by 2 rounds of cell rearrangement and 2-3 rounds of cell division (cell rearrangement occurred mediolaterally, so each round was defined as a halving of the number of cells in the width of the graft and a doubling of the number of cells in its length; each round of cell division was defined as a doubling of graft cell number). Modeling studies demonstrate that these amounts of cell rearrangement and division are sufficient to approximate the shaping of the neural plate that normally ensues during neurulation, provided that some of the cell division occurs within the longitudinal plane of the neural plate and some within its transverse plane: longitudinal cell division results in craniocaudal extension of the neural plate, whereas transverse cell division results in lateral expansion of the neural plate such as that occurring at its cranial end; cell rearrangement results in craniocaudal extension of the neural plate as well as in its narrowing. In conclusion, our results provide evidence that shaping of the neural plate involves mediolateral cell rearrangement and cell division, with the latter occurring within both the longitudinal and transverse planes of the neural plate. PMID- 2598818 TI - Fibronectin gene expression during limb cartilage differentiation. AB - A critical event in limb cartilage differentiation is a transient cellular condensation process in which prechondrogenic mesenchymal cells become closely juxtaposed and interact with one another prior to initiating cartilage matrix deposition. Fibronectin (FN) has been suggested to be involved in regulating the onset of condensation and chondrogenesis by actively promoting prechondrogenic aggregate formation during the process. We have performed a systematic quantitative study of the expression of the FN gene during the progression of chondrogenesis in vitro and in vivo. In high-density micromass cultures of limb mesenchymal cells, FN mRNA levels increase about 5-fold coincident with the crucial condensation process, and remain relatively high during the initial deposition of cartilage matrix by the cells. Thereafter, FN mRNA levels progressively decline to relatively low levels as the cultures form a virtually uniform mass of cartilage. The changes in FN mRNA levels in vitro are paralleled closely by changes in the relative rate of FN synthesis as determined by pulse labeling and immunoprecipitation analysis. The relative rate of FN synthesis increases 4- to 5-fold at condensation and the onset of chondrogenesis, after which it progressively declines to low levels as cartilage matrix accumulates. High levels of FN gene expression also occur at the onset of chondrogenesis in vivo. In the proximal central core regions of the limb bud in which condensation and cartilage matrix deposition are being initiated, FN mRNA levels and the relative rates of FN synthesis become progressively about 4-fold higher than in the distal subridge region, which consists of undifferentiated mesenchymal cells that have not yet initiated condensation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598820 TI - Analysis of specific mRNA destabilization during Dictyostelium development. AB - A number of specific mRNAs are destabilized upon disaggregation of developing Dictyostelium discoideum cells. Analysis of a family of cloned genes indicates that only prespore-enriched mRNAs are affected; constitutive mRNAs that are expressed throughout development and mRNAs that accumulate preferentially in prestalk cells are stable under these conditions. The decay of sensitive prespore mRNAs can be halted by allowing the cells to reaggregate, indicating that destabilization occurs by the progressive selection of individual molecules rather than on all members of an mRNA subpopulation at the time of disaggregation. Individual molecules of the sensitive mRNA species remain engaged in protein synthesis in the disaggregated cells until selected. Destabilization of sensitive mRNAs is induced by cell dissociation even in the presence of concentrations of nogalamycin that inhibit RNA synthesis. The reported prevention of disaggregation-induced mRNA decay by actinomycin D and daunomycin is therefore probably a secondary effect unrelated to the inhibition of transcription. PMID- 2598819 TI - Analysis of lens cell fate and eye morphogenesis in transgenic mice ablated for cells of the lens lineage. AB - Transgenic mice carrying the diphtheria toxin A gene driven by mouse gamma 2 crystallin promoter sequences manifest microphthalmia due to ablation of fiber cells in the ocular lens. Here we map ablation events in the lens by crossing animals hemizygous for the ablation construct with transgenic mice homozygous for the in situ lacZ reporter gene driven by identical gamma 2-crystallin promoter sequences. By comparing the spatial distribution of lacZ-expressing cells and the profile of gamma-crystallin gene expression in the lenses of normal and microphthalmic offspring, the contributions of specific cell types to lens development were examined. The results suggest that phenotypically and developmentally distinct populations of lens fiber cells are able to contribute to the lens nucleus during organogenesis. We also show that dosage of the transgene and its site of integration influence the extent of ablation. In those mice homozygous for the transgene and completely lacking cells of the lens lineage, we show that the sclera, cornea, and ciliary epithelium are reduced in size but, otherwise, reasonably well formed. In contrast, the anterior chamber, iris, and vitreous body are not discernible while the sensory retina is highly convoluted and extensively fills the vitreous chamber. PMID- 2598821 TI - Influence of extracellular matrix proteins on the expression of neuronal polarity. AB - The influence of laminin (LN) and fibronectin (FN) on the differentiation of individual neurones from the embryonic rat central nervous system was studied in vitro. In control cultures or in the presence of soluble FN, most neurones had several dendrite-like and one axon-like processes. On substratum-bound LN, multipolar and unipolar cells were present. Soluble LN and bound FN induced a very simple neuronal morphology, most neurones having only one axon-like neurite as defined by morphological and immunocytochemical characteristics. The significant reduction of neuronal adhesion and spreading in conditions leading to the growth inhibition of dendrite-like processes suggests that, contrary to that of axons, dendrite growth strongly depends on neuronal adhesion. We propose a model in which the different dependency of axonal and dendritic outgrowth towards adhesion and spreading is explained by the respective physical properties of the two types of neurites. PMID- 2598822 TI - Two UV-sensitive targets in dorsoanterior specification of frog embryos. AB - Previous work has shown that ultraviolet (UV) irradiation of fertilized frog eggs yields embryos that lack dorsal and anterior structures. The eggs fail to undergo the cortical/cytoplasmic rotation that specifies dorsoventral polarity, and they lack an array of parallel microtubules associated with the rotation. These eggs can be rescued by tilting with respect to gravity, and normal dorsoanterior development occurs. We find here that UV irradiation of Xenopus prophase I oocytes or Rana metaphase I oocytes also causes the dorsoanterior deficient syndrome, but the UV target is different from that in fertilized eggs. Tilting eggs, irradiated as oocytes, with respect to gravity, does not rescue dorsoanterior development, although lithium treatment does. The UV dose required to produce dorsoanterior deficiency for Rana metaphase I oocytes is much less than that for fertilized eggs, and the oocytes can form the array of parallel microtubules and undergo the cortical/cytoplasmic rotation after fertilization. Despite these features of normal development, no dorsoanterior structures form. While the UV target in fertilized eggs is thought to be the parallel microtubules (Elinson & Rowning, 1988; Devl Biol. 128, 185-197), the UV target in the oocytes may be a dorsal determinant. PMID- 2598823 TI - Xenopus mesoderm induction: evidence for early size control and partial autonomy for pattern development by onset of gastrulation. AB - Experiments are described that examine the state of organisation of the presumptive mesoderm and ectoderm of the Xenopus embryo at stages up to the onset of gastrulation. It is shown that a process during blastula stages, establishing the normal proportions in which this cell population is partitioned to found the two outer 'germ layers', has a positive regulative property. An operation has been performed to excise the yolky endodermal core, at the beginning of gastrulation, leaving only the presumptive territories of mesoderm, neural tissue, epidermis and supra-blastoporal endoderm. This reveals that by this time a stable capacity exists within the induced tissue to express the craniocaudal sequence of the normal pattern, including the proper numbers of somite segments. The mediolateral organisation of such body patterns is however abnormal. The relevance of the observations to understanding mechanisms of axial pattern control is discussed. PMID- 2598824 TI - Temporal changes in the expression of the insulin-like growth factor II gene associated with tissue maturation in the human fetus. AB - The insulin-like growth factors are broadly distributed in the human conceptus and are thought to play a role in the growth and differentiation of tissues during development. Using in situ hybridization we have shown that a wide variety of specific cell types within tissues express the gene for insulin-like growth factor II at times of development from 18 days to 14 weeks of gestation. Examination of blastocysts produced by in vitro fertilization showed no expression, thus bracketing the time of first accumulation of IGF-II mRNA to between 5 and 18 days postfertilization. The pattern of IGF-II expression shows specific age-related differences in different tissues. In the kidney, for example, expression is found in the cells of the metanephric blastema which is dramatically reduced as the blastema differentiates. The reverse is also seen, and we have noted an increase in expression of IGF-II in the cytotrophoblast layer of the placenta with gestational age. The sites of expression do not correlate with areas of either high mitotic activity or specific types of differentiation, but the observed pattern of expression in the kidney, adrenal glands and liver suggests an explanation for the abnormally high IGF-II mRNA expression in developmental tumours such as Wilms' tumour. PMID- 2598825 TI - Blastocyst implantation precedes induction of insulin-like growth factor II gene expression in human trophoblasts. AB - The cytotrophoblast cell population of the human embryonic conceptus proliferates rapidly during the first month following blastocyst implantation. Since the trophectoderm lineage is established in preimplantation morula/blastocysts, the scenario underlying initiation and maintenance of the rapid proliferative phenotype of cytotrophoblasts is a central issue. The insulin-like growth factor II (IGF-II) gene is highly expressed in proliferative cytotrophoblasts of first trimester placenta and performs as a placenta growth factor. To establish a temporal correlation between IGF-II expression and initiation of highly proliferative trophoblasts in human development, we employed in situ hybridization analysis of the expression of the IGF-II and human chorionic gonadotropin beta-subunit (beta-HCG) genes in human pre- and postimplantation development. The data show that the appearance of high steady-state levels of IGF II transcripts in trophoblasts is a postimplantation event, whereas beta-HCG transcripts can already be detected in preimplantation development. This observation makes a role for endogenously produced IGF-II in the normal development of preimplantation embryos unlikely, but suggests that endogenously produced IGF-II participates in the formation and subsequent expansion of the rapid proliferative phenotype of the trophoblastic shell, following implantation. PMID- 2598826 TI - Amounts and modulation of actin mRNAs in mouse oocytes and embryos. AB - In order to measure the content of beta- and gamma-actin mRNA in mouse oocytes and ovulated eggs, Northern and slot blots were hybridized to complementary RNA probes transcribed from mouse isotype-specific cDNA sequences. The blots included samples of isotype-specific sense strand RNA standards prepared from the same cDNA sequences. Total actin mRNA content was estimated to be 40 fg per preovulatory full-grown oocyte or egg, consisting of one-third beta-actin mRNA and two-thirds gamma-actin mRNA. Ninety per cent of the actin mRNA is on polysomes in full-grown oocytes. The per cent of actin mRNA in polysomal mRNA is similar to the per cent of actin in newly synthesized proteins. Measurements on other developmental stages showed that, in mid-growth-phase oocytes, each actin mRNA reaches a level twofold higher than in full-grown oocytes. Thereafter, all modulations of the two isotypic mRNAs occur in parallel; that is, they are maintained at constant levels during the late growth phase (oocytes from females 8-14 days old); gradually degraded in oocytes that have completed their rapid growth phase (oocytes from females 15-18 days old), in maturing oocytes, and in 1 and 2-cell embryos; and deadenylated after about 7 h of progression into meiotic maturation. PMID- 2598827 TI - Exclusionary dendritic interactions in the retina of the goldfish. AB - The retina of the goldfish grows throughout its life, in part, by the addition of new neurons at the margin. New ganglion cells added at the margin tend not to grow their dendritic arbors into the older, central retina. Hitchcock and Easter (J. Neurosci. 6, 1037-1050 (1986)) proposed that the dendrites of the new cells were prevented from extending centrally within the inner plexiform layer by the dendrites of the previous generations of cells. This proposal was tested by first killing existing ganglion cells with a retrogradely transported neurotoxin (propidium iodide; PI), and then observing the orientation and branching pattern of the dendrites of ganglion cells added subsequently at the margin. Dendrites were stained in retinal wholemounts by intracellular injections of Lucifer yellow. The data showed that cells added subsequent to the PI treatment grew their dendritic arbors preferentially toward central retina consistent with the hypothesis. It is concluded that interactions among adjacent ganglion cells regulates dendritic growth. PMID- 2598828 TI - The effects of dietary iron supplementation on the toxicity of piroctone olamine in the growing rat. AB - Weanling Charles River CD rats of both sexes were fed 300 mg/kg/day of Piroctone Olamine, an anti-bacterial agent, and were supplemented with 0, 50, 100 or 200 ppm dietary iron as FeSO4.7H2O for six weeks. However, analytical data indicated that Piroctone was degraded in the diet so that the rats received only 225 mg/kg/day. The rats given Piroctone Olamine without iron gained significantly less body weight and ate significantly less feed than controls, with the effect being more pronounced in the males. They also developed severe microcytic, hypochromic anemia. The rats supplemented with all three levels of dietary iron grew at a rate similar to controls. The rats supplemented with 50 ppm dietary iron had anemia with all of the hematological iron-associated factors being significantly depressed. The 100 ppm supplement restored all hematologic factors to normal in the females, but slight reductions remained in the males. The 200 ppm supplement of iron restored all parameters to values similar to the controls in both sexes. These results suggest that the mechanism of the toxicity of Piroctone Olamine is the prevention of dietary iron absorption by in situ chelation. PMID- 2598829 TI - Evaluation of teratogenic potential of sodium sulfite in rats. AB - The teratogenicity of sodium sulfite was examined in Wistar rats. The pregnant rats were fed diets containing 5, 2.5, 1.25, 0.63 or 0.32% of sodium sulfite heptahydrate(Na2SO3.7H2O) ad libitum from day 8 to 20 of pregnancy. Maternal toxicity, as evidenced by decreased body weight gain and decreased food consumption was observed at the 5% group, but no clinical signs of toxicity were observed. A significant reduction in the fetal body weight of both sexes was observed in all dose groups except 2.5% group. No significant differences in the numbers of live fetuses and intrauterine death (dead fetuses and resorptions) or sex ratios of fetuses were found between the sodium sulfite-treated and control groups. Fetal external, skeletal and internal malformations were not observed at any dose level. However, several types of skeletal and internal variations as well as delayed ossifications were observed in some groups treated with sodium sulfite, but the incidences were not significantly different from controls. Also, some fetuses with dilatation of the renal pelvis and the lateral ventricle were found in all groups except 1.25% group, but there was no dose-response. The live birth index and survival rate of offspring within 4 weeks and their body weight gain at 3 weeks after birth were not affected by sodium sulfite-treatment. In conclusion, sodium sulfite (0, 0.32, 0.63, 1.25, 2.5 or 5.0% as Na2SO3.7H2O) administered in the diet to Wistar rats during days 8-20 of pregnancy produced related signs of fetal toxicity but no evidence of teratogenicity. PMID- 2598830 TI - Penetration studies and residue determinations of 2,4-dichlorophenoxyacetic acid butyl ester in fertile hen eggs and chicks hatched from treated eggs. AB - Fertilized hen eggs were topically applied with 2,4-Dichlorophenoxyacetic acid butyl ester (3.1 mg/egg) before starting incubation. During the incubation time 20% of the compound applied on eggs was lost by volatilization. At different incubation times (0, 1, 5, 10 and 15 days) the wash-off technique was applied to fertile hen eggs and residue analyses of 2,4-D ester were determined and quantified by gas chromatography with an electron capture detector. We found that 2,4-D ester began to be detectable at the embryo from the 5th incubation day and the amount of the compound progressively increased during chick embryonic development. Furthermore chicks hatched from treated eggs showed the presence of the compound in all studied tissues and the highest levels were found in organs such as brain and kidney. PMID- 2598831 TI - Physiological responses in rats fed extracts of endophyte-free and endophyte infected tall fescue seed relative to some known ergot alkaloids. AB - Ethanol and ethanol-water extracts of endophyte-infected tall fescue seed were effective for extracting toxin(s) responsible for feed intake and average daily weight gain (ADG) depression in Sprague Dawley rats. Although the ethanol extract of endophyte-infected seed depressed serum prolactin (Prl) concentrations, the data were less reflective of overall toxicity than feed intake and weight gain. Inclusion of commercially available ergonovine maleate, ergocryptine and ergotamine tartrate had no effect on rat feed intake, ADG or serum Prl at the levels tested. Dietary addition of a recombination of hexane, ethanol and ethanol water extracts caused a toxicity response (depressed feed intake, ADG, and serum Prl) equivalent to that of the whole seed. The toxic factor(s) were extracted primarily in more polar solvents such as ethanol and ethanol-water. Rat assays can be used successfully in lieu of cattle assays as a routine evaluation of toxic components in endophyte-infected tall fescue. However, species differences dictate that eventually all suspected toxins be evaluated in the bovine. PMID- 2598832 TI - Short term toxicity study in rats dosed with isoeugenol benzyl ether. AB - Isoeugenol benzyl ether was given to rats by gavage for 28 days at 0, 60, 120, and 240 mg/kg body weight/day. For both sexes at the highest dose and females at the intermediate dose statistically significantly decreased values were found for body weight, blood glucose (also for males at intermediate dose), blood urea and relative liver weights. No dose-related histopathological changes were seen in any organs. The no effect level was 60 mg/kg body weight/day. PMID- 2598833 TI - Studies of the developmental toxicity of polycarboxylate dispersing agents. AB - Three linear polycarboxylate compounds, two linear polyacrylates (90,000 MW and 4,500 MW) and one linear polyacrylate-maleate copolymer (12,000 MW), were tested for their teratogenic potential in female Sprague Dawley rats. These polymers, which were tested as sodium salts, are used as dispersing agents in detergent formulations at levels of 1-5%. All compounds were administered by gavage during organogenesis (days 6-15 of pregnancy). No adverse effects on development were seen with any of the three compounds at any of the doses tested. The highest dose, and therefore the minimum no-effect dose, for the three linear polymers was 1125 mg/kg/day for the 90,000 MW polyacrylate, 3000 mg/kg/day for the 4,500 MW polyacrylate, and 6670 mg/kg/day for the polyacrylate-maleate copolymer. Based on these data, these compounds are not developmentally toxic, even at very high dose levels. PMID- 2598834 TI - [What is the outcome of popularizing medical science?]. PMID- 2598835 TI - [The danger of medical news in the mass media]. PMID- 2598836 TI - [The health market]. PMID- 2598837 TI - [The physician and the public message]. PMID- 2598838 TI - [Is there a difference between the physician's language and the in- formed patient?]. PMID- 2598839 TI - [Should the patient be addressed by his first name?]. PMID- 2598840 TI - [One patient, many doctors]. PMID- 2598841 TI - [When patients refuse treatment]. PMID- 2598842 TI - [Health promotion or pills?]. PMID- 2598843 TI - [Difficult patients or difficult doctors?]. PMID- 2598844 TI - [Doctors, nurses and patients]. PMID- 2598845 TI - [When a child has a serious illness, who explains and how?]. PMID- 2598846 TI - [What is to be reported to the surgical patient?]. PMID- 2598847 TI - [Approaches to cancer]. PMID- 2598848 TI - [Comparative management in the treatment of pediatric diabetes]. PMID- 2598849 TI - [The patient's psychiatric encounters]. PMID- 2598850 TI - [Knowledge requirements, security and suffering in genetic diseases]. PMID- 2598851 TI - [What medical data should be reported to clinical trial partici- pants?]. PMID- 2598852 TI - [Conservative dentistry in aged patients]. AB - Aging is a physiologic process. There are basically no agedependent limits to conservative dentistry--neither in the treatment of caries nor in the field of endodontics or periodontics. The teeth and their supporting structures undergo changes in the course of a lifetime. This must be taken into consideration when deciding on the method to be applied in the treatment of diseases. PMID- 2598853 TI - [Surgical treatment of the aging patient]. AB - Surgery in the elderly patient calls for a particular approach, since the physical powers of older persons are generally compromised, age-induced pathological organ alterations are frequent and the structures of skin, mucosa and bone have undergone physiological changes. Regarding the use of anesthetics and premedication, impaired hepatic and renal function will often require considering drugs with a prolonged half life and selecting low dosages. Although the surgical procedures required are basically the same as in the younger age groups, these operations are often considerably complicated by sclerosing of the surrounding bone and the associated risk of a jaw fracture. The majority of the elderly patients treated by the oral surgeon present with painful TMJ arthroses or rheumatoid arthritides, fractures of the visceral cranium accompanied by soft tissue injuries, tumors, or conditions requiring preprosthetic surgery. In older persons all these procedures demand specific indications, operative techniques and aftercare. PMID- 2598854 TI - [Masticatory forces and maximum jaw closure forces of complete denture wearers before and after bite opening]. AB - The maximum jaw closure forces and the masticatory forces during the comminution of soft and though food were measured with changing vertical dimensions. The maximum jaw closure force was reduced by a mean 25% in all patients after the vertical dimension had been increased. Significant reductions in the masticatory forces were found only on the working side with the forces decreasing rather during the chewing of soft than tough food. Thus, in chewing sour drops the average masticatory force was 32.9 N as against 46.6 N, whereas in chewing bread it dropped to 21.3 N as against 42.8 N. The study showed that increasing the vertical dimension in endentulous patients up to an interocclusal clearance of 0 mm resulted in a functional impairment of speech and mastication and, above all, in sore spots and inflammations of the mucosa. PMID- 2598855 TI - [Cuspid protection and muscular reaction]. AB - In an epidemiological study we found bilateral cuspid guidance in only 4, and unilateral cuspid guidance in 3 patients out of 247 patients examined. This suggest that cuspid guidance is a rare form of articulation. In the experimental part of this study the electric activity of the masseter and anterior temporal muscles was measured during empty mastication before and after the canines were treated with build-ups in a patient group with muscular and TMJ problems and matched against the results obtained in a control group of 10 healthy probands. Apart from the mean muscle activity also the path of excursion was recorded. Both values were combined in activity/path diagrams providing information on the muscular response to different forms of occlusion. Existing balancing contacts in mediotrusion, for instance, may produce high activities. With cuspid build-ups allowing correct cuspid guidance the patients with muscular and TMJ problems were symptom-free after just three days. After approx. one year the patients and the probands were recalled for a follow-up check. These and other results are discussed. PMID- 2598856 TI - [Quantitative studies on the secretory output of the palatine salivary glands]. AB - A method for the direct measurement of the secretory output of the palatine glands is described and its clinical reliability is verified in a study on 134 persons. The results showed that, if the measuring conditions are fulfilled and the measuring parameters are kept constant, the error remains below 15%. Situative influences, such as the time of the day, the date of the measurement, etc. are just of secondary importance for the measured results. The physiological secretory output of the palatine glands averages 1.36 microliters/mm2 mucosal surface, which is about 30 times as much as the values measured in patients with symptoms of hyposalivation. Personal characteristics of the persons tested such as age, sex, etc. have no major influence on the secretory output. Serial measurements during treatment with ptyalagogues supported the evidence that this measuring method is a valuable instrument in the diagnosis of salivation disorders. PMID- 2598857 TI - [The correlation among pulp chamber, tooth length and tooth width in different age groups]. AB - Computing the quotients of pulp chamber length/tooth length and pulp chamber width/tooth width for canines and lower premolars on orthopantomograms of subjects aged between 19 and 65 years led to the following result: significant reduction in length quotient and highly significant reduction in width quotient with increasing age. The reduction in width was considerably greater than in length. PMID- 2598858 TI - [Determining the threshold level for sensibility responses to galvanic potentials in the oral cavity]. AB - The presence of different alloys in the oral cavity may produce potential differences of up to 900 mV. In the majority of the patients this phenomenon presents no problems. Occasionally, however, disturbing sensations, such as "metallic taste", "twinging or stabbing" and "minute electric shock" are reported. In finding out on the threshold level for discomforting sensations due to galvanic potentials in different probands, a special battery operated device was developed. Using a pair of electrodes connected to metallic restorations in the mouth, this device enabled the application and adjustment of direct current voltage and a superimposed pulse spectrum to evoke sensible reactions. The trials were conducted with 102 probands. The mean value for the threshold of sensation was above 1000 mV. In solitary cases, however, the threshold level was as low as 250 mV. This method may be used as a diagnostic aid to the objective assessment of complaints due to galvanic effects in the oral cavity and for the selection of a suitable metal in sensitive patients. PMID- 2598859 TI - [Quantitative comparison of the secretion of salivary and mucous glands]. AB - The flow rates and the Na+/K+ quotients of the saliva from the parotid and palatine glands were determined by direct comparison in 121 patients. The results showed that the flow rates and the Na+/K+ quotients of the same types of glands were not correlated with each other. Pronounced and specific interrelations as to the amount of secretion were observed only in patients complaining about dry mouth or smarting of the mucosa or patients under chronic treatment with psychoactive drugs where secretory inhibition is a side effect. The evaluation of the Na+/K+ quotients demonstrated that the secretion examined was almost exclusively resting saliva secretion. Based on these observations it is important that our understanding of the control mechanisms governing the activities of the different gland types within the masticatory system be reassessed. PMID- 2598860 TI - [Enamel and dentin under the ultrasonic microscope]. AB - Ultrasonic reflection scanning microscopy is a new method for imaging the known structures of dental hard tissues on the basis of a simple specimen preparation. The specimens are scanned in a physiologic humid environment. Particularly high contrast images are obtained from enamel tufts and lamellae, dentin tubules and interglobular dentin. PMID- 2598861 TI - [Effects of preparation geometry on compressive strength of crown-like glass ceramic test specimens]. PMID- 2598862 TI - [Comparison of two operative techniques for odontogenic maxillary sinusitis]. AB - The bone lid method introduced by Lindorf (1974) was compared with a conservative procedure leaving a small defekt in the malar buttres. The operation is partly done with an endoscope. The results of 60 operated maxillary sinuses show a higher incidence of dysesthesia and postoperative discomfort in the bone lid method. Thus this method should in our opinion be reserved to special indications. PMID- 2598863 TI - [Biological testing and clinical assessment of composite restorations]. AB - The vital-microscopic acute pulp test in rat incisors did not show any toxic effects of the light-curing composite material Lux-a-fill, independent of the remaining dentin thickness. The clinically controlled 2-year study of restorations of cavity class I, III, IV and V have yielded good results in the front teeth region. In addition to the clinical study a micromorphological follow up study of the surface morphology was performed in cavity class I, and small restorations have been found clinically acceptable after 2 years. Despite of the good results further medium term studies are needed for extended restorations in posterior teeth. The combination of biological application tests in an adequate animal experiment and highly standardized clinical studies is a important prerequisite for the introduction of new filling materials. PMID- 2598864 TI - [Radiosterilization of impressions]. AB - Dimensional stability and mechanical properties of addition-silicone impression materials were tested after sterilisation with gamma rays. There were no clinically relevant changes to not sterilized materials. PMID- 2598865 TI - [Fracture resistance of human maxillary molars with MOD amalgam or composite fillings]. AB - The fracture resistance of human maxillary molars was tested following different types of cavity preparation and filling with various materials. The untreated controls and teeth treated with amalgam/Dentin Adhesive showed the highest strength values. A comparable fracture resistance was found in teeth with amalgam or composite fillings and direct composite inlays, these values being significantly lower than in the controls. The lowest strength values measured were those of the unfilled teeth with prepared cavities. PMID- 2598866 TI - [Application of fibrin adhesive systems in the maxillary sinus as an alternative to tamponage]. AB - During the past two years 22 patients with a chronic maxillary sinusitis have been operated in our clinic using a special catheter set for the application of fibrin glue instead of a gauze strip tamponade as a hemostypt. With 20 of these patients the results of this method were evaluated in a clinical investigation. All investigated sinuses were clinically, roentgenologically and sonographically asymptomatic, as were also sinuscopic controls with a part of these patients. PMID- 2598867 TI - [Alterations of teeth and jaws in children with chronic renal failure]. AB - Dental examination of 50 children with chronic renal failure revealed enamel hypoplasia in 26 (52%), retardation of dental age in 18 (36%) and delay of dental eruption in 16 (32%) cases. In comparison to normal children the prevalence of caries was significantly lower. Half of the children showed radiologic changes in the jaw-bones already during preterminal stage of renal insufficiency. The possible role of the dentist concerning early diagnosis of renal failure is discussed. PMID- 2598868 TI - [Can a maxillodental prosthesis with a permanently elastic extension be a function dynamic replacement for a defective velopharyngeal seal?]. PMID- 2598869 TI - [Microbiological in vitro and animal experiments assessing the cariogenic potential of various snacks]. AB - Microbiological in vitro and animal experiments were performed to determine the cariogenic potential of different snacks. The determination of the oral salivary sugar clearance time by the aid of a cariogenic S. mutans strain as standard for the cariogenic potential resulted in a relatively high clearance time when a praline was consumed, according to a high cariogenic potential. When consuming a "safe for teeth"-product no easily fermenting substances in the saliva can be shown, suggesting a lacking cariogenic potential. The cariogenic potential of banana, milk-chocolate, Milchschnitte, Musli-Frucht-Schnitten (cereals and fruits) is between that of the praline and the "safe for teeth"-product. The animal experiments showed in increasing strength of fissure caries after programmed feeding of the following snacks: Basic-diet----milk-chocolate--- positive control-diet/Milchschnitte Musli-Frucht-Schnitten----banana. The highest caries values occurred after having fed banana, the lowest after having fed milk chocolate. Milchschnitte and Musli-Frucht-Schnitten showed similar caries values which were between the values after feeding of milk-chocolate and banana. PMID- 2598870 TI - [Early development of human tooth germs including the surrounding structures]. AB - It could be shown by means of 3-dimensional reconstructions made from serial sections of human embryos, that the dental lamina of the lower jaw as well as that of the upper jaw is spatially impeded at its distal ends by the presence of the mandible and Meckel's cartilage. This spatial impediment of the odontogenetic epithelium can be seen to be of influence during the formation of the tooth buds. PMID- 2598871 TI - [A selective, need-oriented prevention program for primary schoolchildren - results after two years]. AB - 427 first grade pupils from primary schools in Gottingen participated in a selective, need-oriented preventive program. Following a clinical examination and an additional saliva test the children were assigned to three risk groups, according to the severity of the initial findings. Each group received preventive care of varying intensity. Two years later the children of risk group 1 ("minor caries risk") showed a mean 0.5 and those of risk group 2 ("medium caries risk") a mean 1.0 new DF surfaces. In the children of the high caries risk group the average caries increment was 1.8 DF surfaces. The degree of sanation of the deciduous teeth could be improved from 10% to 47% within the two years' test period. The saliva tests revealed that the number of cariogenic organisms was markedly reduced in the course of the preventive program. PMID- 2598873 TI - [Psychic changes in old age: neurobiological, psychopathological and psychosomatic aspects]. PMID- 2598872 TI - [Age-related changes in the remodeling processes in the alveolar bone area]. AB - It was the aim of this study to show the feasibilities of histomorphometric measurements for quantitative analysis of human alveolar bone remodeling. The principles of the method and the prerequisites for the evaluation of histological sections are presented. PMID- 2598874 TI - [Approach to treating elderly patients in the dental office]. PMID- 2598875 TI - [Recording pattern of occlusal indicators. I. Influence of indicator thickness, pressure, and surface morphology]. AB - There are no data in the literature about the recording pattern of occlusal indicators and the relevant methods. We therefore studied the recording patterns of four foils, six paper materials, and four silk qualities at different pressures and surface morphologies. Foils are the thinnest indicator materials and give more accurate readings than paper and silk. However, under smaller loads their marking capacity is worse. This means that higher pressures must be applied for the clinical use of foils. The drawbacks of the more intensively marking papers and silk are their greater thickness and less flexible base material. This leads to a greater number of pseudo contact markings. PMID- 2598876 TI - [Apical root pins of high-karat gold alloys for resected roots]. AB - Following earlier studies on corrosion of silver pins in the root canal experience will be presented with the use of high-karat gold pins for apical closure of root amputations. The commercially available standardized Ackermann silver pins were replaced by high-karat gold pins of similar Vicker hardness and inserted in 218 patients with 264 root amputations since 1986. A clinical and radiological follow-up demonstrated a success rate of over 90%. PMID- 2598878 TI - Bacteroides spp. in dental root canal infections. AB - A summary of a series of bacteriological studies of endodontic infections is presented in this article. The bacteriology of 62 root canal infections was studied with special attention focused on the occurrence, role and taxonomy of Bacteroides spp. All infections except one were mixed infections dominated usually by anaerobic bacteria. Four to 6 different species were present in most canals. Species of the genus Bacteroides were found more frequently than species of any other genus. Seventy-eight Bacteroides strains were isolated from 45 canals. B. buccae, B. intermedius, B. denticola, B. oris, B. oralis, and B. gingivalis were the most common Bacteroides spp. At the beginning of the treatment 35 of 62 teeth caused acute symptoms. The results indicated that symptoms were a result of the synergistic action of the mixed anaerobic flora. The presence of B. gingivalis, B. endodontalis, and B. buccae was more often related to acute cases than other Bacteroides spp. Black-pigmented Bacteroides and a new Bacteroides-like organism, Mitsuokella dentalis, seemed to increase the probability that acute symptoms would persist one week after the beginning of the treatment. However, the treatment result assessed after 4 weeks and after 1 year was not affected by the composition of the mixed anaerobic flora. Calcium hydroxide was the only canal disinfectant used. Its efficacy was proved by a bacteriological sample at the second appointment in 10 cases. All teeth were asymptomatic at the third appointment. The susceptibility of the isolated Bacteroides strains to penicillin G was also studied. Only 2 B. buccae strains and 2 B. denticola strains were resistant at a concentration of 2.4 micrograms/ml. The patients were randomly divided into 3 groups which received 1) no antibiotics, 2) penicillin V (650 mg x 3) for 7 days, or 3) for 12 weeks. There was no difference between the 3 groups in the healing of the periapical lesion after one year. All patients attended the 1-year control. Fifty cases showed complete healing, partial healing was obtained in 11 cases and in 1 case no healing was observed. PMID- 2598877 TI - Electrophysiologic study of anomalous innervation of the intrinsic hand muscles. AB - With electrophysiological methods the possible presence of anomalous innervation and/or of anastomosis between the median and ulnar nerve in the intrinsic hand muscles was studied in 34 limbs. The abductor pollicis brevis was supplied by the ulnar nerve in 12% to 38%, the first dorsal interosseus by the median nerve in 4.2% to 19.6%; the abductor digiti minimi was in no case supplied by the median nerve. PMID- 2598879 TI - Prognosis of root-fractured permanent incisors--prediction of healing modalities. AB - A population of 85 patients, comprising 95 root-fractured permanent incisors followed up to 11 years, was studied prospectively for the type of fracture healing that occurred (i.e. union of the fragments by interposition of hard tissue (HT) or connective tissue (CT), or nonunion characterized by interposition of granulation tissue between the fragments (GT)). Initial treatment was provided according to established treatment guidelines by the attending oral surgeon at the emergency room. Follow-up examination and treatment were provided by 2 of the authors. It appeared that GT could be diagnosed after approximately 3 weeks, while HT or CT could be diagnosed approximately 6 weeks after trauma. Many factors considered one at a time were found to have a significant or nearly significant effect on the type of fracture healing that occurred. However, a multivariate regression analysis revealed that the following factors were significantly related to fracture healing by HT: a large diameter of the apical foramen and severity of luxation of the coronal fragment (concussion/subluxation greater than lateral luxation greater than extrusion); fracture healing by CT: the presence of restorations in the injured teeth at the time of injury and the presence of marginal periodontal disease; and fracture nonhealing by GT: type of fixation (i.e. orthodontic band fixation versus acid etch or no fixation), antibiotic therapy, a constricted apical foramen, increased loosening of the coronal fragment, and stage of root development (GT never occurred in teeth with open apices). It was previously demonstrated following luxation injuries that type of luxation, stage of root development and type of fixation (orthodontic bands versus acid etch or no fixation) determined the prognosis of pulp survival. It therefore appears that the general factors that are able to predict the type of healing seen after root fracture are the same as those after luxation injuries, supporting the hypothesis that root fractures are another form of luxation injury, this time of only the coronal fragment. PMID- 2598880 TI - In vivo sealing ability of calcium hydroxide-containing root canal sealers. AB - It was the purpose of this study to determine the sealing ability of 2 commercially available calcium hydroxide-containing root canal sealers, CRCS and Sealapex. One hundred sixty single-rooted human teeth were used. The clinical crowns were removed and the roots were cleaned mechanically and by immersion for 24 h in 5% sodium hypochlorite. The root canals were then instrumented to size 80 at the apical foramen and the roots were sterilized by gamma-radiation. Under aseptic conditions the root canals were filled with a gutta-percha master cone size 70 and Sealapex (48 roots), CRCS (48 roots), and a zinc oxide-eugenol type sealer, Roth 801 (50 roots). The coronal aspects of the root canals were then sealed with zinc oxide-eugenol cement. In order to bring the roots and root filling materials in contact with tissue and tissue fluids, the roots were implanted subcutaneously in rabbits for 90 days and 1 year. Leakage as demonstrated by penetration of India ink was evaluated using a stereomicroscope. The best results were obtained with CRCS. Significantly less leakage occurred with both calcium hydroxide-containing sealers than with the traditional zinc oxide-eugenol sealer. PMID- 2598881 TI - A longitudinal study of changes in frequency and technical standard of endodontic treatment in a Swedish population. AB - Longitudinal studies of endodontic treatment are rare. The purpose of this investigation was to study changes in frequency, technical standard and treatment need in a Swedish population with an interval of 5-7 years. The number of endodontically treated teeth in the population increased while the number of periradicular radiolucencies was at about the same level at the second examination. The number of radiolucencies found in endodontically treated teeth was reduced while it was increased in untreated teeth. The number of root fillings ending less than or equal to 2 mm from the apex of the tooth as well as fillings with a proper seal had increased at the second examination, but still only 40.2% ended less than or equal to 2 mm from the apex of the tooth and 59.1% of the root fillings were judged to have a proper seal. It was concluded that a great need for endodontic treatment existed in the population examined. A slight improvement in the quality of the treatment was evident at the second examination. However, the technical standard was still poor and obviously affected the outcome of the treatment. It is the opinion of the authors that endodontic treatment methods should be simplified as much as possible in an effort to improve the technical quality of the treatment. The prognosis of endodontic treatment would then improve as well. PMID- 2598882 TI - Periodontal tissue reactions following root canal obturation with an injection thermoplasticized gutta-percha technique. AB - The thermoplasticized gutta-percha obturation technique is a relatively recent development in endodontics. In this study we evaluated the possible effects of heat transmitted to the periodontal tissues when the Obtura root canal filling device was used in dog teeth. Two 8-month-old beagle dogs were used; 56 root canals of 36 teeth (maxillary incisors and first, second and third premolars of both jaws) were divided into two groups. In Group A 26 root canals were obturated with the lateral condensation technique, while in Group B 30 root canals were obturated using the Obtura device, without sealer. Observation periods were 1, 3, 7, 28 and 56 days. After routine laboratory procedures, hematoxylin-eosin stained sections were examined under a light microscope. In this experimental model the thermoplasticized gutta-percha obturation technique caused a periapical inflammatory reaction at all observation periods. Inflammatory reaction and destruction of collagen fibers were localized in the area around the apical delta, while the alveolar founding bone, the roots of the teeth and the periodontal ligament at the side of the root surfaces remained normal. PMID- 2598883 TI - Progression of root resorption following replantation of human teeth after extended extraoral storage. AB - Avulsed human permanent teeth subjected to a minimum of 1 h dry extraoral storage before replantation were followed radiographically for an average of 4.8 years. The depth of root resorption cavities was assessed using a radiographic index, and the rate of root resorption was defined as the index change over time. The frequency of inflammatory and replacement resorption was determined at each observation time. Replacement resorption increased in frequency with time in all patients. In teeth endodontically treated within 3 weeks of replantation, minimal inflammatory resorption was found regardless of the age of the patients. In teeth where endodontic treatment was performed more than 3 weeks after replantation, the frequency of inflammatory resorption was significantly higher in young patients but not in older patients, up to more than 3 years after replantation. The rate of root resorption was found to be related to age. In patients 8-16 years old at the time of avulsion the rate of root resorption was significantly higher compared with patients 17-39 years old. Age had a higher impact on the rate of root resorption compared with the delay in endodontic treatment after replantation. It was concluded that a tooth replanted with a necrotic periodontal membrane will become ankylosed and resorbed within 3-7 years in young patients, whereas a tooth replanted under similar conditions in older patients may remain in function for a considerably longer time. PMID- 2598884 TI - Pulpal pathosis and severe alveolar lesions: a clinical study. AB - Gingivitis is widely believed to be the precursor of crestal alveolar bone destruction (periodontitis) in some individuals. However, there is no correlation between gingivitis and severe localized lesions of alveolar bone. Specific 'periodontopathogens' of the indigenous oral flora are hypothesized to be the cause of localized lesions but the evidence to date is one of association only. Acute and chronic pulpal inflammation are known causes of irritation to the periodontal ligament and alveolar bone; retrograde pockets may subsequently form. Contamination by indigenous organisms best adapted to the special environment of the deep pocket could be expected to follow the establishment of the new conditions. This study was undertaken to examine the clinical and histological status of the pulps of teeth affected by severe localized alveolar lesions. A total of 153 teeth in 90 subjects were studied; full periodontic and endodontic assessments were made. Seventy-seven teeth responded in the normal range to pulp testing, but 52% of these had no recoverable tissue from their root canal systems on endodontic opening. The findings indicated that pulpal pathosis was not clinically detectable in the majority of teeth studied when conventional endodontic diagnostic tests were applied. Rather, the presence of localized severe alveolar defects was a more accurate predictor of pulpal pathosis. PMID- 2598885 TI - Ultrasound in endodontics: a quantitative and histological assessment using human teeth. AB - Hand instrumentation of the root canal was compared with ultrasonic instrumentation in 20 maxillary premolars with 2 root canals. The buccal and lingual canals were alternately instrumented by the 2 techniques until they had reached clinically ideal conditions for filling. After mechanical preparation, an attempt was made to evaluate root shape and the enlarging ability of the 2 techniques. For this purpose, a crosswise cut slice approximately 100 microns thick was cut off at the middle level of the root, which permitted comparative quantification of the instrumented area of the buccal and lingual canals. Crosscut serial sections of the remaining parts of the root were obtained for a systematic study of the entire extension of the root canal. It was concluded that the presence of debris inside the root canal depended more on the anatomical variation of the canal than on the technique used. No statistically significant differences in root canal area were evident at the middle third level of the root. PMID- 2598886 TI - Surgical-restorative treatment of bleaching-related external root resorption. AB - Three teeth in 2 patients were treated after intracoronal bleaching with 30% hydrogen peroxide had resulted in external root resorption. An attempt to treat one tooth by placing an intracoronal dressing with calcium hydroxide had failed. The resorption defects were exposed surgically by reducing and re-contouring the alveolar crest. The restorations were made during the surgical procedure, with a light-cured composite in one case and with amalgam in the other, and were of compromised quality due to the difficulty of control. One year follow-up examinations revealed periodontal complications in both cases, in the form of a further resorption of the alveolar crest and gingival edema. These sequelae suggested that the restoration of bleaching-related resorption defects should have been a secondary stage, after the surgical exposure of the defects had been completed first. For the purpose of exposing the defects, the level of the alveolar crest should be reduced enough to secure a biological width from the restorations. PMID- 2598887 TI - Differentiation of radicular cyst and granulomas using computerized tomography. AB - The purpose of this investigation was to study periapical lesions by means of computerized tomography to ascertain if this noninvasive method could be of value in distinguishing between radicular cysts and granulomas. Periapical radiographs were taken of the teeth of 60 human cadavers. Periapical radiolucencies were seen in conjunction with 33 teeth. Based on the periapical radiographs, an oral radiologist (J.P.) attempted to select 4 granulomas and 4 cysts from the 33 radiolucencies. Computerized tomography was performed on the root tips and the periapical lesions of these 8 teeth. The roots and periapical lesions were then surgically removed and prepared histologically for microscopic examination. In the tomographs, 7 of the periapical lesions had a cloudy appearance with a density similar to each other and to the surrounding soft tissue. In the eighth lesion a homogeneous dark area with a distinctly lower density could be distinguished from surrounding cloudy areas. Histologically, the dark area was shown to be an epithelialized cyst cavity. The other 7 lesions were granulomas. Thus, a cyst could be differentiated from periapical granulomas by computerized tomography because of a marked difference in density between the content of the cyst cavity and granulomatous tissue. PMID- 2598888 TI - Effects of two gutta-percha formulations and one zinc oxide-eugenol and Canada balsam mixture on human blood monocytes and lymphocytes. AB - In this study we performed an in vitro assay of the effects of two gutta-percha formulations and one zinc oxide-eugenol and Canada balsam-based endodontic material on the behavior of a mixed cell population of human monocytes and lymphocytes. Cells were cultured either in direct contact with or near experimental samples of Ultrafil, standard gutta-percha cones or Endoseal and the inhibitory effects of these materials upon cell attachment and spreading on test surfaces were analyzed. Ultrafil and the standard gutta-percha cones showed little or no adverse effects, whereas the inhibitory effects of Endoseal appeared to be severe. There were statistically significant differences between the results obtained from both Ultrafil and gutta-percha cones and those obtained from Endoseal. Differences between all tested materials and their respective controls were also statistically significant. PMID- 2598889 TI - An analysis of breakage of ultrasonic files during root canal instrumentation. AB - The incidence of fracture of Cavi-Endo ultrasonic K-files during ultrasonic root canal preparation was evaluated. In addition, the appearance and the sites of fractures were examined in relation to the nodal points on the file. The displacement amplitudes and the hardness of the files were quantified to determine their relationship to fracture. It was observed that the files exhibited a low incidence of fracture, which was of the brittle type and occurred at the apical ends. The displacement amplitude and the hardness of the files did not appear to influence the incidence of fracture. PMID- 2598890 TI - Effect of ultrasonic instrumentation on Bacteroides intermedius. AB - Two physical mechanisms of ultrasound, cavitation and acoustic streaming, were investigated in an ultrasonic endodontic unit. In addition, the potential of ultrasonic instrumentation for disruption of Bacteroides intermedius was examined at various time intervals. The ultrasonic file could not generate cavitation within the recommended power settings indicated for endodontic purposes. However, there was evidence of acoustic streaming. The latter phenomenon resulted in destruction of 21.6%, 30.4% and 92.9% of test bacteria after 1, 5 and 15 min sonication respectively. It appears that ultrasonic instrumentation of root canals has little bactericidal effect. PMID- 2598891 TI - Sealing ability of thermoplasticized gutta-percha in root canal obturation using a sectional vs. a single-phase technique. AB - Properly prepared straight root canals of freshly extracted maxillary canines and central incisors were used to evaluate the sealing ability of the sectional thermoplasticized gutta-percha obturation technique, with or without sealer and the single-phase thermoplasticized gutta-percha filling technique. The teeth were divided into 3 groups (A, B, C) of 20 teeth and were obturated using the 3 thermoplasticized gutta-percha techniques. Group A: single phase with sealer; group B: sectional technique without sealer; and group C: sectional technique with sealer. The obturated teeth were immersed in India ink for 3 days followed by clearing procedures. The teeth were then examined under a stereo microscope and the linear leakage was recorded. Statistical unpaired Student's t-tests showed significantly less dye penetration in teeth obturated using the sectional technique with sealer (group C) than in teeth obturated with the single-phase technique with sealer (group A) or the sectional technique without sealer (group B). PMID- 2598892 TI - Iron, folic acid and zinc intakes and status of low socio-economic pregnant and lactating Amazonian women. AB - Dietary intakes were obtained by 24-h recall from 25 women in the first and third trimesters of pregnancy and 25 women in the first 3 months of lactation from eight towns in the Amazon valley. No consistent differences were found between the towns, so the results have been analysed together. Intakes of iron, free and total folate and zinc were nearly all very low compared with current recommendations. Despite their low intakes, the majority of the women had acceptable values of haemoglobin, haematocrit and MCHC. Serum folate concentrations were almost all extremely low (less than 2.5 ng/ml). The levels of RBC folate were also low, but in general not as severely so as those for serum folate. Serum zinc concentrations ranged from 0.2 to 0.7 microgram/ml, whereas the lower limit of acceptability has been put by various authors as 0.59-0.69 microgram/ml according to the stage of pregnancy. In breast milk, total folate in the majority of women ranged from 25 to 50 ng/ml, the greater part of it being in the free form. Zinc levels in breast milk were within the range 0-2 microgram/ml. PMID- 2598893 TI - Energy expenditure/basal metabolic rate ratios in normal and marginally undernourished Colombian children 6-16 years of age. AB - Measurements of basal (BMR) and resting (RMR) metabolic rates, maintenance (MEE) and total daily energy expenditures (TDEE) have been made in Colombian children 6 16 years of age classified as nutritionally normal (boys, n = 129; girls, n = 72) and marginally undernourished (boys, n = 171; girls, n = 74). TDEE/BMR ratios were calculated for comparison with those suggested by FAO/WHO/UNU (1985) and to provide data for children less than 10 years of age. TDEE was measured in free living, individually calibrated subjects by the heart-rate method. TDEE/BMR increased significantly with age in boys from 1.60 to 1.84 in control subjects and 1.46 to 1.92 in undernourished boys. There was no significant increase with age in the girls. There were no statistically significant differences between nutritional groups but girls had significantly lower values than boys. There was a greater rate of increase in TDEE than BMR with age and girls spent more time in light activities and less in high level activities than boys. PMID- 2598894 TI - Iron absorption and phenolic compounds: importance of different phenolic structures. AB - The phenolic compounds (phenolic monomers, polyphenols, tannins) are considered to interfere with iron absorption by complex formation with iron in the gastro intestinal lumen, making the iron less available for absorption. Very little is known about the extent to which different types of phenolic compounds of different size and chemical structure inhibit iron absorption. The relationship between iron absorption and the amount and type of phenolic compounds was studied by the extrinsic tag method. The aims of the studies were as follows: (i) To study the effect of small phenolic compounds with different hydroxylation patterns (gallic acid, catechin, chlorogenic acid) on iron absorption, (ii) To study the effect of different amounts of a hydrolysable tannin containing ten gallic acid residues (tannic acid) on iron absorption. (iii) To study the degree of inhibition of iron absorption by some foods and beverages (oregano, spinach, coffee and tea) in relation to their respective content of iron-binding phenolic groups, measured by a newly developed method. The inhibition of iron absorption by tannic acid was strongly dose-related. The smallest amount (5 mg) inhibited absorption by 20 per cent, 25 mg by 67 per cent and 100 mg by 88 per cent. Gallic acid inhibited iron absorption to the same extent as tannic acid, per mol galloyl groups, whereas no inhibition was observed when catechin was added to the test meal. Chlorogenic acid inhibited iron absorption to a lesser extent. Oregano and tea inhibited iron absorption in proportion to their respective content of galloyl groups, whereas the inhibitory effect of spinach was less marked. The inhibiting effect of coffee was explained mainly by its content of galloyl groups, but also by some other factor, probably chlorogenic acid. It is concluded that the content of iron-binding galloyl groups might be a major determinant of the inhibitory effect of phenolic compounds on iron absorption from the diet, whereas the phenolic catechol groups seem to be of minor importance. The results further suggest that the group of condensed tannins do not interfere with iron absorption. PMID- 2598895 TI - Is an adaptation of Siri's formula for the calculation of body fat percentage from body density in the elderly necessary? AB - Using data from the literature on changes in the mineral content, muscle mass and the amount of water in the body during aging, the age-related changes in the chemical composition of the fat-free mass have been calculated. In men the decrease in minerals (bone loss) during aging equals the decrease in protein and water (muscle) in the fat-free mass. As a consequence the chemical composition of the fat-free mass is hardly affected by aging in men. In women, however, the loss of minerals during aging is considerably higher than the decrease in protein and water in the fat-free mass. As a consequence the change in the chemical composition of the fat-free mass in females is remarkable, and therefore in females, the density (kg/l) of the fat-free mass decreases with age. Consequently the body fat percentage calculated from body density with Siri's equation overestimates the real body fat percentage by 2-3 per cent, depending on age. Based on the calculated chemical composition of the fat-free mass at several ages, and its calculated theoretical density, Siri's equation has been adapted. In females but not in men the adapted formulas give a more valid estimate of the body fat percentage calculated from body density compared to Siri's formula. PMID- 2598896 TI - In obese subjects the body fat percentage calculated with Siri's formula is an overestimation. AB - By means of theoretical calculations it is shown that the chemical composition of the fat-free mass is affected by the amount of fat in the body. With increasing fatness the relative amounts of minerals and protein in the fat-free mass will decrease and the relative amount of water will increase. These changes in the chemical composition of the fat-free mass are confirmed by data from the literature. Because minerals and protein are the most dense components in the fat free mass, and water is the less dense component, the density of the fat-free mass will decrease with increasing body fatness. As a consequence, the normally used computation formula for the calculation of the body fat percentage from whole-body density (Siri's equation) will systematically overestimate the real body fat percentage by as much as 2-4 per cent in severely obese subjects. This overestimation is large enough to correct for in studies on energy metabolism and body composition. PMID- 2598897 TI - Nutrition policy in Norway. PMID- 2598898 TI - Nutrition policy development and implementation in Malta. AB - The paper highlights experiences in the development and implementation of the food and nutrition policy in Malta. As one could expect there has been tangible progress in certain areas but less so in others. Some background information on the food and health status of the Maltese population is given first as this was the reason for the establishment of the policy in Malta in the first place. PMID- 2598899 TI - Nutrition policy in Greece. AB - The development of the efforts towards a nutrition policy in Greece during the last decade is described. These efforts are discussed in the context of information about the contemporary dietary patterns of the Greek population, obtained from FAO food balance sheets and the national household budget surveys. PMID- 2598900 TI - The Mediterranean diet in Spain. AB - The purpose of this paper is to assess the food habits of the Spanish population and the composition of the fat consumed. The national food survey data have been used. This survey was carried out during one week in a representative sample of households by means of recorded weighing or the household measures method. The main characteristics of the diet is tha considerable amounts of vegetables (393 g), fruits (283 g), milk and dairy products (383 g) and fish (72 g) are consumed. The total fat intake amounts to 131-g 73 g from vegetable, and 56 g from animal origin, 2 g from fish. The composition of the lipid intake was 36 g of SFA, 61 g of MUFA and 21 g of PUFA with a contribution to energy consumption of 11%, 19% and 7% respectively. The latter is highly influenced by the olive oil consumed in Spain. Although food habits and the quality of the lipids are satisfactory, trends during the last 15 years show an increased consumption of energy from fat (from 30% to 40%). A nutrition policity based on nutrition information to keep traditional Spanish food patterns would be perhaps in the best interests of this country. PMID- 2598901 TI - Elements of nutrition policy in Portugal. AB - A nutrition policy, as defined by WHO (Elizabet Helsing), has not yet been approved by the Portuguese Parliament. Several nutrition programmes have, however, been implemented, the following being the most important; the school milk programme, started in 1973; several programmes on nutrition education for the general public carried out since 1974; the programme for promotion of success in school, started in 1987, covering several areas, including free food supplementation and the WHO CINDI Programme, a community intervention programme aimed at reducing common chronic disease risk factors, started, in Portugal, 1987, in the district of Setubal, a pilot area, with a population of 740,000. PMID- 2598902 TI - Sleep, smoking and performance. PMID- 2598903 TI - The dynamic response of a subject seated on various cushions. AB - An impact pendulum was used to examine the dynamic response of the seated subject. The dynamic response is of interest in establishing the relationship between driving and low-back pain. Accelerometers were placed on the seat and in vivo at the L3 vertebra. The transmissibility and phase angle were obtained in the frequency domain for a variety of cushions. Soft cushions were found to increase the gain at the first natural frequency. PMID- 2598904 TI - Whole-body vibration in underground load-haul-dump vehicles. AB - Whole-body vibrations (WBV) were measured at the seatpan of load-haul-dump (LHD) vehicles of 3.5-, 5-, 6- and 8-yard capacity at two underground mines. Twenty-two sets of measurements were made involving 11 vehicles, 8 operators and 4 work locations. In each set frequency-weighted rms and peak accelerations were measured in the x, y and z directions, as defined by the ISO (1982), during mucking, driving full, dumping and driving empty. Significant differences in rms accelerations were found between vehicle sizes and between operational tasks (less than or equal to 0.05). The smallest (3.5 yd) vehicle produced the greatest accelerations in the x and z directions. Accelerations in the x and z directions were also greater when driving full and empty than when mucking and dumping. The highest frequency-weighted rms accelerations of 2.0 to 2.8 m/s-2 were recorded in the z (longitudinal) direction. Peak accelerations ranged from 1.2 to greater than or equal to 20 m/s2, resulting in crest-factor ratios in excess of six. The exposure periods for each task were used to calculate mean daily acceleration exposures (m/s2). Of the 22 sets of measurements, 20 exceeded the International Standards Organization (ISO) six-hour daily exposure limit in the z direction of acceleration, and 9 exceeded the six-hour daily exposure limits in all three directions. Acceleration exposure ratios calculated using resultant acceleration vectors as described in ISO (1982), were found to exceed the ISO exposure limit for health or safety in all 22 cases. One-third octave band frequency analysis of the weighted signals indicated that the dominant frequencies were usually 1.6 to 3.15 Hz, except when the vehicles were idling and higher frequencies predominated. PMID- 2598905 TI - The influence of a 1 h nap on performance overnight. AB - The effect on performance overnight of a 1 h nap taken at 0200 h was studied in six young female subjects. The subjects completed three schedules, including one with a nap and two without a nap, during which either a placebo or 300 mg caffeine was ingested at 2315 h. Performance was measured from 1700 h in the evening until 1030 h the next morning. Caffeine improved performance overnight on almost all tasks compared with placebo. The nap had some limited beneficial effect compared with placebo, but most tasks remained impaired. PMID- 2598906 TI - The effect of passive smoking on vigilance performance. AB - The present experiment was designed to test for effects of passive smoking on vigilance performance as well as to determine whether smokers and non-smokers are differentially affected by exposure to passive smoking. Four groups of subjects were used--smokers and non-smokers working in either clean or smoky air--and measures of decision time, movement time, correct detections, d' and beta, were obtained together with ratings of mood. The results show that sensitivity and accuracy of both smokers and non-smokers was detrimentally affected by passive smoking, and that the onset of the effect was earlier for the non-smoking subjects than for the smoking subjects. In addition, passive smoking significantly reduced decision time for the non-smoking subjects although movement time and beta were not significantly affected by exposure to the smoky environment. The findings indicate that both smokers and non-smokers may be adversely affected by passive smoking although effects may not appear until some time has elapsed. Data obtained from the mood scale show that feelings of anger and annoyance are increased by exposure to smoke and it is suggested that these feelings may contribute to the observed performance deficits. PMID- 2598907 TI - Nutrient costing. AB - For the purpose of computing changes in food cost over time as well as the planning of proper nutrition education and dietary counselling, the cost of important Ethiopian foods was collected in Addis Ababa markets for three and one half years and computed for the amount of energy and protein yield per unit price. In general, cereals and legumes faired well in their contribution of these nutrients at low cost. Certain foods, such as vetch, sugar and marmalades were also found to contribute a significant amount of nutrients at low cost. Because of the neurotoxic content in vetch and the contribution of a single nutrient as an energy source in the case of the latter two, their utilization during meal planning is subject to careful consideration. Foods of animal origin are second to last in their nutrient contribution per cost although their nutrient density makes them important in consumer demand. Root crops and vegetables that are known for their bulk are at the bottom of the list of good nutrient contributors per cost. PMID- 2598908 TI - Prevalence of body lice in elementary school students in three Ethiopian towns at different altitudes. AB - A survey of body lice in three different altitudinal zones of Ethiopia was conducted. The survey population consisted of primary school children of both sexes ranging in age from 6-25 years. The areas of study were Gambela, Kemise and Debre-Berhan. Only 33.2% of the school children were found to be free from infestation and the rest, 66.8%, harboured body lice ranging in number of 1 to 598. The prevalence in Debre-Berhan (76.2%) was found to be significantly higher (p less than 0.001) than in Gambela (61.4%) and Kemise (62.6%). Similarly the density of lice was higher (P less than 0.001) among Debre-Berhan than among Gambela or Kemise school children. Infestation was commoner among the 11-15 and 16-20 year than the 6-10 and 21-25 year ago groups. There was no difference in the prevalence of lice between the sexes but a higher density was observed among males. The importance of having prior knowledge of the prevalence and abundance of body lice in different areas has been discussed in relation to possible outbreaks of louse-borne diseases. PMID- 2598909 TI - Incidence and some perinatal problems of multiple pregnancies in a central referral hospital, Addis Ababa. AB - This survey covers 41,645 deliveries registered in St. Paul's Hospital, Addis Ababa (one of the 6 central referral hospitals of Ethiopia), from 1971 to 1985, with multiple deliveries comprising 2.5% of all the cases. The results obtained from analysis of these data revealed that twins occurred in the ratio of 1:41 deliveries, and triplets in 1:41(2) deliveries, this is in conformity with Hellin's statement, made in 1895. The occurrence of multiple delivery in multigravidae is shown as 1.62 times greater than that in primigravidae. There was a male predominance (52.1%) among twins. Discordant twins and triplets were observed in 31.5% and 50% respectively. In 55.9% of twin deliveries, both twins had a birthweight of less than 2500g. Head presentation of both twins occurred in 40% of the multiple births. Operative delivery was undertaken in 12.4% of all the cases. PMID- 2598910 TI - Penetrating chest injuries. AB - The purpose of this paper is to review our experience in the management of penetrating chest injuries and their outcome in spite of the shortage of equipment for thoracic surgery at the Gonder Hospital. The study was based on prospective analysis of 32 cases treated at this hospital between February 1987 and February 1988. About 30% of our cases has associated injuries to other organs. Simple pleural space drainage was done in 19 cases. Only 4 of the patients required immediate or delayed thoracotomy while 3 other cases required laparotomy. Complications occurred in 8 patients, of whom 6 died. In 6 cases only conservative treatment was indicated. About 80% of our patients with penetrating chest chest injuries were treated successfully with no, or only minimal, residual defects. Availability of of simple and effective materials in rural hospitals is recommended. PMID- 2598911 TI - Gangrenous sigmoid colon secondary to twisted pedunculated left ovarian tumour. AB - A case of strangulated sigmoid colon secondary to a twisted left ovarian tumour in an 18 year old female is presented. No similar case was identified in the literature. PMID- 2598912 TI - The effect of decreased muscle energy stores on the VO2 kinetics at the onset of exercise. AB - The kinetics of adjustment of oxygen uptake (VO2) at the onset of a square wave of exercise in man has been shown to be variable and related mainly to factors located distal to the capillary. The present study examined the effects of decreasing oxygen and high energy phosphates (approximately P) stores, by blood flow occlusion (BFO) and/or preceding exercise, on the half time of the VO2 on response (t1/2 VO2 on-) during arm exercise. Twelve male subjects performed an arm exercise test at a standard intensity of 75 W (75 WA) following six procedures designed progressively to decrease O2 and/or approximately P stores. Breath-by-breath VO2 and lactic acid accumulation in blood (delta [1ab]) during the VO2 transient were measured. Preceding the 75 WA by 5 min of 125 W leg exercise decreased significantly the t1/2 VO2 on- (63-47 s). Preceding the 75 WA with either arm BFO and isometric exercise (1 min), no-load or 25 W (25WA) arm cranking (5 min) did not significantly affect t1/2 VO2 on- or delta [1ab]. Preceding 75 WA with 5-10 min BFO or BFO plus 25 WA resulted in a significant decrease in t1/2 VO2 on- (20% and 50%, respectively). The delta [1ab] increased linearly with t1/2 VO2 on-responses greater than 24 s. These data suggest that the local depletion of O2 and/or approximately P stores play an important role in determining the kinetics of adjustment of VO2 to exercise. PMID- 2598913 TI - Prediction of the thermoregulatory response for clothed immersion in cold water. AB - A multi-compartmental thermoregulatory model was applied to data of ten resting clothed males immersed for 3 h in water at 10 and 15 degrees C. Clothing consisted of a dry suit and either a light or heavy undergarment, representing a total insulation of 0.15 (0.95) or 0.20 m2 degrees CW-1 (1.28 clo), respectively. Data were grouped according to low (less than 14%) and high (14 to 24%) body fat individuals. Mean decreases in rectal temperature ranged from 0.79 to 1.38 degrees C, mean decreases in the mean weighted skin temperature ranged from 6.3 to 10.2 degrees C, and mean increases in the metabolic rate ranged from 33.9 to 80.8 W. The model consists of eight segments, each representing a specific region of the body. Each segment is comprised of compartments representing the core, muscle, fat, skin, and clothing. Each compartment is assigned thermophysical values of heat conduction and heat capacitance, and with the exception of clothing, physiological values of blood flow and metabolic heat production. During cold exposure, responses are directed towards increased heat production in the form of shivering and heat conservation in the form of vasoconstriction and convective heat exchange at the vascular level. Agreement between the model predictions and the experimental observations was obtained by adjusting the parameters governing these responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598914 TI - Energetics of kayaking. AB - The metabolic cost of paddling at low speeds (v) was measured from oxygen uptake (VO2) and anaerobic glycolysis in an annular pool or calculated from submaximal VO2 measured at higher speeds when the kayaker was assisted in overcoming water resistance. Also calculated were the total drag (D) and the net mechanical efficiency (e). Each of the above variables was determined in male (n = 17) and female (n = 7) kayakers ranging in experience from beginners to elite. The VO2 increased with v to a peak of approximately 3.4 l.min-1 (80%-100% of peak VO2 during running) in men and of approximately 2.8 l.min-1 in women, while at higher speeds the additional energy was accounted for by anaerobic glycolysis. In all subjects the energy cost to paddle a given distance (C) increased according to a power function with increasing v. The C was lower for the elite male paddlers than for the unskilled group, while that for elite women was slightly less than that for the elite men. Also the rates of increase of C appeared to be inversely proportional to the subjects' skill. Total D for elite men increased from approximately 15 to 60 N over a range of speeds from 1 to 2.2 m.s-1 while those of unskilled men and skilled women for the same speed range were 10-20 N greater and slightly less, respectively. The e increased linearly, but at a different rate, with increases in v for the unskilled and the elite kayakers (males and females) being 4.2% and 6%, respectively, at v = 1.2 m.s-1. PMID- 2598915 TI - Strength gains in obese females are unaffected by moderate dietary restriction. AB - This study examined the effects of dietary restriction on strength gains from whole body resistance training. Comparisons were made between diet-restricted (n = 12) and non-diet-restricted (n = 10) obese women (mean +/- SD, 36.7 +/- 7.0% fat) undergoing identical 8-week resistance training regimens. Diet-restricted subjects reduced their dietary intake by 4200 kJ/day and reduced body mass by 3.9 kg over 8 weeks. Ten-repetition maximum masses were compared between the groups on biweekly intervals. Results indicated no differences between the groups with respect to the rate or magnitude of strength gains for any of the eight exercises. Significant pre- to post-test increases in strength (p less than 0.05) were found for all eight exercises. The rate or magnitude of strength gains induced by resistance training does not appear to be affected by moderate dietary restrictions in obese females. PMID- 2598916 TI - The effect of clothing on "diving bradycardia" in man during submersion in cold water. AB - Eighteen healthy male volunteers undertook three seated submersions into stirred water at 5 degrees C. Whilst submerged, the subjects attempted to hold their breath for 20 s. They wore a different clothing assembly for each submersion, viz: a cotton overall assembly, a "wet suit" assembly and a "dry suit" assembly. During the experiments the breath-hold time, heart rate, skin and rectal temperatures of the subjects were recorded. The results showed that significantly (P less than 0.05) more subjects developed a diving bradycardia--defined as five or more consecutive R-R intervals of over 1.2 s--when wearing the dry suit. It is concluded that increasing the cold stress experienced by individuals during cold water submersion decreases the incidence of diving bradycardia but not the magnitude of the bradycardia when it occurs. PMID- 2598917 TI - The effects of specificity of training on rating of perceived exertion at the lactate threshold. AB - To determine the effects of cycle and run training on rating of perceived exertion at the lactate threshold (LT), college men completed a 40-session training program in 10 weeks (n = 6 run training, n = 5 cycle training, n = 5 controls). Pre- and post-training variables were measured during graded exercise tests on both the bicycle ergometer and treadmill. ANOVA on the pre- and post training difference scores resulted in similar improvements in VO2max for both testing protocols, regardless of training mode. The run training group increased VO2 at the LT by 58.5% on the treadmill protocol and by 20.3% on the cycle ergometer. Cycle trainers increased VO2 LT only during cycle ergometry (+38.7%). No changes were observed in the control group. No differences for RPE at the LT were found before or after training, or between testing protocols for any group. Perception of exercise intensity at the LT ranged from "very light" to "light". The relationship between RPE and %VO2max was altered by the specific mode of training, with trained subjects having a lower RPE at a given %VO2max (no change in RPE at max.). It was concluded that RPE at the LT was not affected by training, despite the fact that after training the LT occurs at a higher work rate and was associated with higher absolute and relative metabolic and cardiorespiratory demands. PMID- 2598918 TI - The relationship between muscle kinetic parameters and kinematic variables in a complex movement. AB - Kinematic variables of the vertical jump (jumping height, jump phase durations and joint angles) were measured on 39 male physical education students. In addition, kinetic parameters of the hip and knee extensors, and of the plantar flexors (maxima voluntary force and its rate of development) were recorded on the same subjects, in isometric conditions. The results demonstrated significant positive correlations between kinetic parameters of the active muscle groups and jumping height (r = 0.217-0.464). The dominant effect on these correlations was due to the knee extensors. Correlations between these parameters and the duration of the jump phases were much weaker. Correlation coefficients between kinetic parameters and limb angles in the lowest body position showed that fast force production in one muscle group was related to a significant decrease in the joint angles of distant body segments. Multiple correlation coefficients between leg extensor parameters and kinematic variables (ranging between 0.256 for the duration of the counter-movement phase and 0.616 for jump height) suggested that kinetic parameters could explain more than a quarter of the variability of this complex human movement. Therefore, the conclusion was drawn that an extended set of measurements of the relevant musculo-skeletal system parameters could predict a considerable amount of the variability of human movement. However, high correlation coefficients between the same kinetic parameters of different muscle groups suggest that not all active muscle groups have to be included in the measurements. PMID- 2598919 TI - Dynamics of changes in the cardiovascular response to submaximal exercise during low-intensity endurance training with particular reference to the systolic time intervals. AB - Eighteen male volunteers (aged 20-23 years), not involved in any sporting activities, were submitted to 13 weeks of training consisting of 30 min exercise [at 50%-75% maximal oxygen intake (VO2max)] on a cycle ergometer, performed 3 times a week. Every 4 weeks cardiac function was evaluated by measuring the systolic time intervals at rest and during submaximal cycle exercise. Stroke volume (SV), heart rate (HR) and blood pressure (BP) responses to submaximal exercise, VO2max and anaerobic threshold (AT) were also determined. Significant increases in VO2max, increases in AT and SV at the submaximal exercise intensities, as well as decreases in HR and BP were found after 4 weeks of training. Resting systolic time intervals were not affected by training, but during the submaximal cycle exercise the values of the pre-ejection period (PEP) and isovolumic contraction time (ICT) corresponding to HR of 100 beats.min-1 were significantly lowered after 13 weeks of training, whereas PEP, ICT and total electromechanical systole corresponding to HR of 130 beats.min-1 were significantly shortened by the 4th week. The ratios of PEP:LVET (left ventricular ejection time) and ICT:LVET during submaximal exercise were significantly lowered by training starting from the 8th week. These changes might be interpreted as evidence of the training-induced enhancement of the "contractility reserve", i.e. the ability to increase heart muscle contractility with increasing exercise intensity. PMID- 2598920 TI - Changes in ventilation at the end of heavy exercise of different durations. AB - The purpose of this study was to examine the effects of duration and the concomitant ventilatory drift of heavy exercise on the changes in ventilation following the cessation of exercise. Seven male subjects ran on a motor-driven treadmill at a constant work-rate of 90% of VO2max for either 5 min or 7 min on 60 occasions. The exercise was terminated abruptly by stopping the treadmill with a remote switch while recording inspired minute ventilation (VI) breath by breath. The fast drop in VI at the end of exercise is significantly less than the corresponding increase at the onset of exercise (P less than 0.05) and this difference is greater with longer duration of exercise. The time constants of the slow ventilatory decline are significantly increased following 7 min of exercise (P less than 0.05). They are also positively related to the drift in VI that occurs with the continuation of heavy exercise beyond 3 min. This relationship is however not statistically significant (P greater than 0.05). These results indicate that the rate of ventilatory decline is slower after the end of a longer duration of exercise and this is caused by mechanism/s that also contribute/s to the ventilatory drift of heavy exercise. As, of the many different possibilities, only the respiratory after-discharge (central neural reverberatory) mechanism is likely to be more activated with a longer duration of exercise and on the basis of our previous observations (Jeyaranjan et al. 1988, 1989), the results suggest that the mechanism of after-discharge is an important mediator of ventilatory response during as well as after the cessation of heavy exercise. PMID- 2598922 TI - Nomenclature of initiation, elongation and termination factors for translation in eukaryotes. Recommendations 1988. Nomenclature Committee of the International Union of Biochemistry (NC-IUB). PMID- 2598921 TI - Elasticity changes in the large arteries of human limbs in response to cycle ergometry performed with upper and lower limbs. AB - At rest and after cycle ergometry the elastic properties of the large arteries of limbs of healthy men were examined using an original non-invasive quantitative oscillometric method. It has been shown that in response to muscle work performed with the legs there is a decrease of the effective inner radius, and an increase of the characteristic impedance modulus and bulk modulus and of the elastic resistance of the intact and relaxed wall in the large arteries in the upper limbs. All these changes testify to an increase of vascular tension in the upper limbs. In response to work performed with the hands, there is an increase of the effective inner radius of large arteries of the upper limbs, a large increase of the pulsatile blood volume increment of the intact vessels and a decrease of the characteristic impedance modulus, of the bulk modulus and of the elastic resistance of the intact arterial wall. These changes indicate a decrease of the vascular tension of these arteries. In response to work performed either with the legs or with the hands a decrease of the effective inner radius of large arteries and an increase of the elastic resistance of the relaxed arterial wall were observed in the lower limbs, all these changes indicating relatively small changes in tone of these vessels. It is concluded that the wall tension of large arteries supplying blood to the muscles of non-working limbs is increased. Vascular tension changes in the arteries in working limbs are accounted for by the superimposition of centrally originating vasoconstriction with local vasodilatation, which also affects large arteries. PMID- 2598923 TI - Pike eel (Muraenesox cinereus) gonadotropin. Amino acid sequences of both alpha and beta subunits. AB - The amino acid sequences of pike eel gonadotropin alpha and beta subunits have been determined by standard sequencing analytical methods. The alpha subunit is composed of 93 amino acid residues while the beta subunit comprises 113 amino acid residues. All the invariant half-cystine residues are in the same positions as those found in other gonadotropins. It is noteworthy that the first, putative glycosylation site (Asn56) found in the alpha subunit of other gonadotropins was replaced by Asp56 in the alpha subunit of pike eel gonadotropin. Similarity analyses indicate that both subunits are structurally more similar to other known fish gonadotropin subunits than to those of the mammalian gonadotropins. PMID- 2598924 TI - Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl CoA reductase kinase activities. AB - 1. We have purified the AMP-activated protein kinase 4800-fold from rat liver. The acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA(HMG-CoA) reductase kinase activities copurify through all six purification steps and are inactivated with similar kinetics by treatment with the reactive ATP analogue fluorosulphonylbenzoyladenosine. 2. The final preparation contains several polypeptides detectable by SDS/polyacrylamide gel electrophoresis, but only one of these, with an apparent molecular mass of 63 kDa, is labelled using [14C]fluorosulphonylbenzoyladenosine. This is also the only polypeptide in the preparation that becomes significantly labelled during incubation with [gamma 32P]ATP. This autophosphorylation reaction did not affect the AMP-stimulated kinase activity. 3. In the absence of AMP the purified kinase has apparent Km values for ATP and acetyl-CoA carboxylase of 86 microM and 1.9 microM respectively. AMP increases the Vmax 3-5-fold without a significant change in the Km for either protein or ATP substrates. 4. The response to AMP depends on the ATP concentration in the assay, but at a near-physiological ATP concentration the half-maximal effect of AMP occurs at 14 microM. Studies with a range of nucleoside monophosphates and diphosphates, and AMP analogues showed that the allosteric activation by AMP was very specific. ADP gave a small stimulation at low concentrations but was inhibitory at high concentrations. 5. These results show that the AMP-activated protein kinase is the major HMG-CoA reductase kinase detectable in rat liver under our assay conditions and that it is therefore likely to be identical to previously described HMG-CoA reductase kinase(s) which are activated by adenine nucleotides and phosphorylation. The AMP-binding and catalytic domains of the kinase are located on a 63-kDa polypeptide which is subject to autophosphorylation. PMID- 2598925 TI - A theoretical treatment of damped oscillations in the transient state kinetics of single-enzyme reactions. AB - An extension of the available kinetic theory for reactions in the transient state is presented which establishes that single-enzyme reactions may exhibit damped oscillations under the conditions of standard kinetic experiments performed by stopped-flow techniques. Such oscillations may occur for reasonable magnitudes of rate constants in the enzymic reaction mechanism and at physiological concentrations of enzyme and substrate. In the simplest reaction systems, the oscillations will be strongly damped and lead to progress curves resembling those of a reaction governed by standard exponential transients; statistical regression methods may then have to be applied for their detection and characterization. The observation that single-enzyme reactions may exhibit oscillatory behaviour points to a previously unrecognized possible source of the damped oscillations observed in metabolic systems such as the pathways of glycolysis or photosynthesis. PMID- 2598926 TI - Occurrence of free and esterified lipoxygenase products in leaves of Glechoma hederacea L. and other Labiatae. AB - Leaves of Glechoma hederacea L. and other Labiatae contain (9S,10E,12Z,15Z)-9 hydroxy-10,12,15-octadecatrienoic acid, (10E,12Z,15Z)-9-oxo-10,12,15 octadecatrienoic acid, (9S,10E,12Z)-9-hydroxy-10,12-octadecadienoic acid and (10E,12Z)-9-oxo-10,12-octadecadienoic acid in a ratio of 71/14/12/3 (by mass), predominantly esterified in the membrane ester lipids. The leaves contain the highest level of these products, whereas only small amounts were found in the stalk and the roots. The chemical structures of these compounds were established by ultraviolet and infrared spectroscopy, by co-chromatography with authentic standards on various types of HPLC columns including chiral-phase HPLC and gas chromatography/mass spectrometry. The stereochemical specificity indicates the enzymatic origin of the products, most probably via a lipoxygenase reaction. Freshly harvested specimens of G. hederacea L. contain only small amounts of hydroxy-polyenoic fatty acids. Air-drying causes a strong increase in the content of free and esterified (9S,10E,12Z,15Z)-9-hydroxy-10,12,15-octadecatrienoic acid. Up to 80% of the hydroxy fatty acids of the total lipid extracts were esterified in the cellular lipids. The data presented indicate that lipoxygenase products occur in the cellular ester lipids of G. hederacea L. and other Labiatae. The results are discussed in the light of a possible involvement of the lipoxygenase pathway in the natural senescence of leaves. PMID- 2598928 TI - Gangliosides of sea urchin embryos. Their localization and participation in early development. AB - The influence of antibodies to gangliosides of sea urchin Strongylocentrotus intermedius eggs on early embryos of this species was studied. gamma-Globulins were isolated from rabbit anti-ganglioside serum by micropreparative electrophoresis. These gamma-globulins produced anomalies in the development of embryos permeabilized in Triton X-100. The anomalies were not observed when anti ganglioside gamma-globulins were added to the incubation medium together with gangliosides or when the permeabilized embryos were incubated with gamma globulins of normal rabbit serum. Pretreatment of S. intermedius embryos with serotonin, tryptamine or some other indole derivatives led to the disappearance of ganglioside determinants from the cell surface and sharply increased immunofluorescence within the cell. Such pretreatment of embryos increased the amount of cell-associated gangliosides more than threefold as compared to untreated embryos. Serotonin was shown to bind specifically to sea urchin gangliosides immobilized on octyl-Sepharose. These observations suggest that cell surface gangliosides, after binding drugs, are internalized and that serotonin and its antagonists inhibit the transport of newly synthesized gangliosides to the cell-surface membrane. PMID- 2598929 TI - Secondary structure of 7SK and 7-2 small RNAs. Possible origin of some 7SK pseudogenes from cDNA formed through self-priming by 7SK RNA. AB - Pseudogenes having homology to small RNAs, like 7SL, 7SK, 6S, 4.5S, U1, U2, and U3 RNAs, are abundant and dispersed in the genomes of higher eukaryotes [reviewed in Weiner et al. (1986) Annu. Rev. Biochem. 55, 631-661]. To understand better the possible origin of these pseudogenes, we studied the abilities of cytoplasmic 7SL, 7SK, and nucleolar 7-2 RNAs to self-prime and result in the synthesis of cDNAs. When rat 7SK RNA was used as substrate, a 294-nucleotide-long cDNA was synthesized in vitro by reverse transcriptase, indicating that the 3' end of 7SK RNA can act in a self-priming manner to generate 7SK cDNA. When 7-2 RNA was used as a substrate, a cDNA of approximately 235 nucleotides was observed; 7SL RNA did not act as a self-primer. Earlier studies have shown that DNAs homologous to 7SK RNA are represented by a moderately reiterated family in the mammalian genomes and many of these sequences were found to be truncated 7SK pseudogenes [Murphy et al. (1984) J. Mol. Biol. 177, 575-590]. In this study, one 7SK clone from the rat genome was characterized by sequencing. This clone contained 243 base pairs homologous to the 5' end of 7SK RNA, and was flanked by direct repeats. These data suggest that, as previously proposed for some U3 pseudogenes [Bernstein et al. (1983) Cell 32, 461-472], one mechanism for the generation of truncated 7SK pseudogenes may be the integration of self-primed reverse transcripts of 7SK RNA at random genomic sites. PMID- 2598927 TI - Differential effects of alpha-, beta- and gamma-cyclodextrins on human erythrocytes. AB - Alpha-, beta- and gamma-cyclodextrins are cyclic hexamers, heptamers, and octamers of glucose, respectively, and thus are hydrophilic; nevertheless, they have the ability to solubilize lipids through the formation of molecular inclusion complexes. The volume of lipophilic space involved in the solubilization process increases with the number of glucose units in the cyclodextrin molecule and, consequently, cyclodextrins were found to have different effects on human erythrocytes: (a) in the induction of shape change from discocyte to spherocyte the potency was observed to be alpha greater than gamma, but with beta-cyclodextrin hemolysis occurred before the change was complete; (b) in the increase of fluorescence intensity of 1-anilinonaphthalene-8 sulfonate in cyclodextrin-pretreated membranes, the observed potency was beta much greater than gamma greater than alpha; (c) in the release of potassium and hemoglobin, the potency was beta greater than alpha greater than gamma. The potencies of cyclodextrin for solubilizing various components of erythrocytes were alpha greater than beta much greater than gamma for phospholipids, beta much greater than gamma greater than alpha for cholesterol and beta much greater than gamma greater than alpha for proteins. The solubilization potencies were derived from concentration/final-effect curves. The above processes occurred without entry of solubilizer into the membrane, since (a) beta-[14C]cyclodextrin did not bind to erythrocytes and (b) cyclodextrins did not enter the cholesterol monolayer. A study of the [3H]cholesterol in erythrocytes indicated that beta cyclodextrin extracted this lipid from membrane into a new compartment located in the aqueous phase which could equilibrate rapidly with additional erythrocytes. Therefore, the effects of cyclodextrins differ from those of detergents which first incorporate themselves into membranes then extract membrane components into supramolecular micelles. PMID- 2598930 TI - Pregnenolone synthesis from cholesterol and hydroxycholesterols by mitochondria from ovaries following the stimulation of immature rats with pregnant mare's serum gonadotropin and human choriogonadotropin. AB - The rate of pregnenolone synthesis by cytochrome P-450scc was measured in mitochondria isolated from ovaries of immature rats treated with pregnant mare's serum gonadotropin and human choriogonadotropin. Using cholesterol, 25 hydroxycholesterol, 20 alpha-hydroxycholesterol, (22R)-22-hydroxycholesterol and (22R)-20 alpha,22-dihydroxycholesterol as substrates, we have determined that the first hydroxylation of cholesterol, in the 22R position, is rate limiting in pregnenolone synthesis. It proceeds at only 22% of the rate of either of the subsequent two hydroxylations. 25-Hydroxycholesterol proved to be a suitable substrate for determining the maximum rate of pregnenolone synthesis by cytochrome P-450scc in isolated mitochondria. The maximum rate was 13 mol steroid.min-1.mol cytochrome P-450scc-1 and did not change after the follicles in the immature ovary had been stimulated to mature and luteinize with gonadotropin. Using endogenous cholesterol in isolated mitochondria as substrate, the time course of pregnenolone synthesis was the same during the follicular phase as in the luteal stage of gonadotropin-induced development. We conclude that during the artificial induced development of follicles in the immature ovary, the major cause of the increase in the rate of pregnenolone synthesis is the increase in the cytochrome P-450scc content of the mitochondria, rather than changes in the catalytic activity of cytochrome P-450scc or the cholesterol availability to the cytochrome. PMID- 2598931 TI - Evidence that 1,3-bisphosphoglycerate dissociation from phosphoglycerate kinase is an intrinsically rapid reaction step. AB - The steady-state kinetics of 1,3-bisphosphoglycerate formation through the action of phosphoglycerate kinase on 3-phosphoglycerate and ATP have been examined. The results show that initial velocities determined by the standard method of coupling bisphosphoglycerate production to NADH reduction in the presence of glyceraldehyde-3-phosphate dehydrogenase do not differ significantly from those determined in the absence of the latter enzyme. This observation invalidates the proposal that bisphosphoglycerate dissociation from phosphoglycerate kinase is much too slow to account for the high rates of phosphoglycerate turnover observed in the coupled two-enzyme system. The capacity for rapid bisphosphoglycerate production and release is an intrinsic catalytic property of phosphoglycerate kinase that does not require the presence of other enzymes or the involvement of a mechanism of channelized (non-diffusional) transfer of bisphosphoglycerate from the producing enzyme to the consuming one. PMID- 2598932 TI - Mechanism of 1,3-bisphosphoglycerate transfer from phosphoglycerate kinase to glyceraldehyde-3-phosphate dehydrogenase. AB - 1. The kinetics of 1,3-bisphosphoglycerate binding to glyceraldehyde-3-phosphate dehydrogenase have been examined by stopped-flow techniques in the absence and presence of phosphoglycerate kinase, using enzyme concentrations in the range 0.5 40 microM. Rate and equilibrium constant estimates for the interaction of the ligand with the two enzymes are reported. 2. The kinetics of ligand transfer from the binary complex of bisphosphoglycerate and phosphoglycerate kinase to the binary complex of NAD+ and glyceraldehyde-3-phosphate dehydrogenase conform excellently to the predictions of a standard free-diffusion mechanism and exhibit no detectable contributions from a mechanism of direct (channelized) transfer of bisphosphoglycerate between the two enzymes. 3. Previously reported evidence that the binary complex of bisphosphoglycerate and phosphoglycerate kinase may act (in the presence of NADH) as a substrate for glyceraldehyde-3-phosphate dehydrogenase according to Michaelis-Menten kinetics is based on a misinterpretation of the experimental observations that can be attributed to neglect of the autocatalytic effect of NAD+ produced during the reaction. Experiments performed under conditions where the autocatalytic effect of NAD+ is eliminated provide clear evidence that the kinetics of utilization of the kinase-bisphosphoglycerate complex for enzymic NADH reduction are consistent with prior dissociation of the complex according to a free-diffusion mechanism of metabolite transfer and incompatible with a mechanism of direct metabolite transfer. 4. A kinetic argument is presented which renders implausible the very idea that direct metabolite transfer between 'soluble' consecutive enzymes in metabolic pathways may offer any catalytic advantages in comparison to metabolite transfer by free diffusion. A mechanism of direct metabolite transfer seems intuitively attractive only because one tends to disregard the diffusional processes required to bring the consecutive enzymes together and to separate them when the transfer has been completed. Direct metabolite transfer would be expected to be catalytically advantageous only in tightly bound multienzyme complexes showing no kinetically significant tendency to dissociate. 5. It is concluded that mechanisms of direct metabolite transfer have not been convincingly demonstrated to apply, nor are they likely to apply, between 'soluble' consecutive enzymes in metabolic pathways, at least not in the glycolytic sequence of reactions. PMID- 2598933 TI - Resonance Raman study on the structure of the active sites of microsomal cytochrome P-450 isozymes LM2 and LM4. AB - The isozymes 2 and 4 of rabbit microsomal cytochrome P-450 (LM2, LM4) have been studied by resonance Raman spectroscopy. Based on high quality spectra, a vibrational assignment of the porphyrin modes in the frequency range between 100 1700 cm-1 is presented for different ferric states of cytochrome P-450 LM2 and LM4. The resonance Raman spectra are interpreted in terms of the spin and ligation state of the heme iron and of heme-protein interactions. While in cytochrome P-450 LM2 the six-coordinated low-spin configuration is predominantly occupied, in the isozyme LM4 the five-coordinated high-spin form is the most stable state. The different stability of these two spin configurations in LM2 and LM4 can be attributed to the structures of the active sites. In the low-spin form of the isozymes LM4 the protein matrix forces the heme into a more rigid conformation than in LM2. These steric constraints are removed upon dissociation of the sixth ligand leading to a more flexible structure of the active site in the high-spin form of the isozyme LM4. The vibrational modes of the vinyl groups were found to be characteristic markers for the specific structures of the heme pockets in both isozymes. They also respond sensitively to type-I substrate binding. While in cytochrome P-450 LM4 the occupation of the substrate-binding pocket induces conformational changes of the vinyl groups, as reflected by frequency shifts of the vinyl modes, in the LM2 isozyme the ground-state conformation of these substituents remain unaffected, suggesting that the more flexible heme pocket can accommodate substrates without imposing steric constraints on the porphyrin. The resonance Raman technique makes structural changes visible which are induced by substrate binding in addition and independent of the changes associated with the shift of the spin state equilibrium: the high-spin states in the substrate-bound and substrate-free enzyme are structurally different. The formation of the inactive form, P-420, involves a severe structural rearrangement in the heme binding pocket leading to drastic changes of the vinyl group conformations. The conformational differences of the active sites in cytochromes P-450 LM2 and LM4 observed in this work contribute to the understanding of the structural basis accounting for substrate and product specificity of cytochrome P-450 isozymes. PMID- 2598934 TI - Control-pattern analysis of metabolic pathways. Flux and concentration control in linear pathways. AB - Metabolic control analysis [Kacser and Burns (1973) Symp. Soc. Exp. Biol. 27, 65 104; Heinrich and Rapoport (1974) Eur. J. Biochem. 42, 89-95] leads to a description of the systemic properties of a metabolic system (expressed as control coefficients) in terms of the local kinetic properties of the individual enzyme-catalyzed reactions (expressed as elasticity coefficients). This paper describes a non-algebraic diagrammatic method which generates the mathematical expressions for flux or concentration-control coefficients in terms of elasticity coefficients. According to a set of simple rules, 'flux-control patterns' or 'concentration-control patterns' are drawn on a metabolic diagram. Each control pattern represents a product of elasticity coefficients that occurs as a term in the expression for a control coefficient. The rules also generate the correct sign that precedes each term. The control patterns are then used to build the expressions for control coefficients. The procedure was developed in such a way that each control pattern can be understood in terms of a 'chain of local effects' which shows how a perturbation in the activity of an enzyme is propagated through the metabolic pathway. PMID- 2598935 TI - Protein-protein interactions in microsomal cytochrome P-450 isozyme LM2 and their effect on substrate binding. AB - The effects of protein-protein interactions and substrate binding on the structure of the active site of rabbit liver microsomal cytochrome P-450 LM2 have been analyzed by resonance Raman spectroscopy of the monomeric and oligomeric protein in solution. Also H2O2-dependent catalytic activities of the two states have been compared. The two vinyl substituents of the heme exhibit different orientations, as indicated by the frequencies and intensities of their stretching vibrations. One group lies in the plane of the heme and remains unchanged in the two states of cytochrome P-450 LM2, the other is tilted out of the plane. The tilting angle in oligomers was smaller than in monomers. These vinyl stretching modes together with some porphyrin modes, were found to be sensitive indicators of the quaternary structure and of substrate binding. In both the oligomer and the monomer, substrate binding causes changes of the relative intensities of some porphyrin modes and the vinyl stretching vibrations which may reflect modifications of the electronic transitions due to hydrophobic interactions between the bound substrate and the heme. In contrast to the monomeric cytochrome P-450 LM2, benzphetamine binding to the oligomers of this isozyme additionally produces a shift of the spin-state equilibrium. This indicates that in the oligomer the substrate-binding pocket is converted by protein-protein interaction to a structure that forces substrates to interfere with the sixth ligands, inducing an increase of the five-coordinated high-spin configuration. In the monomer the substrate-binding pocket can accommodate benzphetamine without affecting the spin state. Binding of imidazole to the monomeric and oligomeric cytochrome P-450 LM2 produces essentially the same resonance Raman spectra. Apparently the replacement of the native sixth ligand by imidazole disturbs the structure of the active site in such a way that it becomes insensitive to protein protein interactions. H2O2-dependent N-demethylation of benzphetamine and aniline p-hydroxylation by cytochrome P-450 LM2 did not depend on its state of aggregation. PMID- 2598936 TI - Structure of sea-urchin arylsulfatase gene. AB - The gene encoding arylsulfatase (Ars; EC 3.1.6.1) as well as two Ars pseudogenes were isolated from sea urchin genomic libraries. The Ars gene was 20-kbp long and contained six exons interrupted by five introns. Four polypyrimidine repetitive sequences were dispersed in its upstream-flanking region. Comparison of the amino acid sequence of sea-urchin arylsulfatase with those of human sterol sulfatase, human arylsulfatase A and bacterial arylsulfatase revealed that they have two similar sequences in common. The position of the transcription-start site of the Ars gene was determined to be approximately 40-bp upstream from the 5' end of the protein-coding region, and the nucleotide sequence of the 5'-flanking region was determined up to 3.3 kbp upstream from the transcription start point. Putative TATAA box and CCAAT consensus sequences were located at positions -28 and -82, respectively. A highly conserved hexamer motif, CTCTTT, localized near the transcription-start site of the sea-urchin Ars gene, was also detected in similar regions of other sea urchin genes such as CyIIIa, Spec 1, Spec 2a, Spec 2c, Spec 2d, and SM50, but not in the histone genes. PMID- 2598937 TI - Short-chain basement membrane collagen. Further characterization and its biosynthesis by F-9 embryonal carcinoma cells. AB - The paper describes further characterization of the 55-kDa short-chain collagen from lens capsule. Lens capsules were extracted with 5.5 M guanidine.HCl and the extracted material was fractionated on agarose A-5M followed by high-pressure liquid chromatography (HPLC). By amino acid composition, the major fraction obtained from HPLC was found to be different than type-IV collagen fragments. The 55-kDa short-chain collagen on pepsin digestion produced a 45-kDa pepsin resistant fragment. The undifferentiated embryonal carcinoma (F-9) cells were found to synthesize increased amounts of 55-kDa short-chain collagen. The identity of this biosynthesized molecule with 55-kDa short-chain collagen from lens capsules was established by immunoprecipitation experiments. The results indicated a close similarity or identical nature of the short-chain collagens from these two sources. PMID- 2598938 TI - Developmental expression of Cu,Zn superoxide dismutase in Xenopus. Constant level of the enzyme in oogenesis and embryogenesis. AB - cDNA clones for Xenopus laevis Cu,Zn-superoxide dismutase were isolated, sequenced and used as probes to study the expression of the corresponding gene during oogenesis and embryogenesis; Cu,Zn-superoxide dismutase activity was also monitored throughout development. It has been observed that its mRNA is actively synthesized during early oogenesis, reaching a maximum level at stage II, and is utilized through oogenesis. This results in an accumulation of enzyme activity during oocyte growth, paralleling the accumulation of the several other cellular components which are stored in the oocyte to be utilized later on by the developing embryo. In fact, Cu,Zn-superoxide dismutase activity is present at an approximately constant level until late embryonic development, while its mRNA disappears soon after fertilization to be accumulated again only during the last part of embryogenesis. This developmental expression behaviour can be viewed as typical of an housekeeping function and suggests that Cu,Zn-superoxide dismutase activity is a constant need of the cell rather than being subject to regulation by oxygen metabolism. PMID- 2598939 TI - 19th Sir Hans Krebs lecture. Engineering of protein bound iron-sulfur clusters. A tool for the study of protein and cluster chemistry and mechanism of iron-sulfur enzymes. AB - An increasing number of iron-sulfur (Fe-S) proteins are found in which the Fe-S cluster is not involved in net electron transfer, as it is in the majority of Fe S proteins. Most of the former are (de)hydratases, of which the most extensively studied is aconitase. Approaches are described and discussed by which the Fe-S cluster of this enzyme could be brought into states of different structure, ligation, oxidation and isotope composition. The species, so obtained, provided the basis for spectroscopic and chemical investigations. Results from studies by protein chemistry, EPR, Mossbauer, 1H, 2H and 57Fe electron-nuclear double resonance spectroscopy are described. Conclusions, which bear on the electronic structure of the Fe-S cluster, enzyme-substrate interaction and the enzymatic mechanism, were derived from a synopsis of the recent work described here and of previous contributions from several laboratories. These conclusions are discussed and summarized in a final section. PMID- 2598940 TI - Rapid intramolecular turnover of N-linked glycans in plasma membrane glycoproteins. Extension of intramolecular turnover to the core sugars in plasma membrane glycoproteins of hepatoma. AB - Plasma membrane glycoproteins of rat hepatocytes undergo a rapid terminal deglycosylation in that the terminal sugars of the oligosaccharide side chains are rapidly removed from the otherwise intact glycoproteins [Tauber, R., Park, C.S. & Reutter, W. (1983) Proc. Natl Acad. Sci. USA 80, 4026-4029]. The present paper demonstrates that this rapid intramolecular turnover of plasma membrane glycoproteins is not restricted to peripheral sugars but, in contrast to liver, in hepatoma the core sugars of the oligosaccharide chains are also involved. Intramolecular turnover was measured in Morris hepatoma 7777 in five plasma membrane glycoproteins with Mr of 85,000 (hgp85), 105,000 (hgp105), 115,000 (hgp115), 125,000 (hgp125), 175,000 (hgp175) (hgp = hepatoma glycoprotein) that were isolated and purified to homogeneity by concanavalin-A--Sepharose affinity chromatography and semipreparative SDS gel electrophoresis. Analysis of the carbohydrates of hgp85, hgp105, hgp115 and hgp125 revealed the presence of N linked oligosaccharides containing L-fucose, D-galactose, D-mannose and N-acetyl D-glucosamine, but only of trace amounts of N-acetyl-D-galactosamine; hgp175 additionally contained significant amounts of N-acetyl-D-galactosamine, indicating the presence of both N- and O-linked oligosaccharides. As shown by digestion with endoglucosaminidase H, the N-linked oligosaccharides of hgp105, hgp115, hgp125 and hgp175 were of the complex type, whereas hgp85 also contained oligosaccharides of the high-mannose type. Half-lives of the turnover of the oligosacharide chains and of the protein backbone of the five glycoproteins were measured in the plasma membrane in pulse-chase experiments in vivo, using L [3H]fucose as a marker of terminal sugars, D-[3H]mannose as marker of a core sugar and L-[3H]leucine for labelling the protein backbone. Protein backbones of the five glycoproteins were degraded with individual half-lives ranging over 41 90 h with a mean of 66 h. Compared to the degradation of the polypeptide backbone, both the terminal sugar L-fucose and the core sugar D-mannose turned over with much shorter half-lives averaging about 20 h in the five glycoproteins. The data show that, conversely to liver, within plasma membrane glycoproteins of hepatoma not only peripheral sugars but also core sugars of the oligosaccharides are split off during the life-span of the protein backbone. It may therefore be assumed that this reprocessing of plasma membrane glycoproteins is sensitive to malignant transformation. PMID- 2598941 TI - Ceramic hydroxyapatite high-performance liquid chromatography of complexes membrane protein and sodium dodecylsulfate. AB - Ceramic hydroxyapatite high-performance liquid chromatography was examined as a chromatographic method by which complexes of whole membrane proteins and sodium dodecyl sulfate could be analyzed. The chromatographic conditions were optimized using the erythrocyte membrane as a model. Whole proteins, including membrane proteins larger than 100 kDa, were eluted as sharp peaks from the column and separated well from each other under optimum conditions. This method gave better resolution of protein-SDS complexes than other chromatographic methods reported so far. The sodium dodecyl sulfate complexes of 24 well characterized proteins were analyzed by this method and their retention times were examined. The positive correlation of the retention time with log (molecular mass) and log sigma (hydrophobicity of amino acids) but not with the isoelectric point, was observed. Based on these results, the mechanism underlying the interaction of protein-SDS complexes with ceramic hydroxyapatite was discussed. PMID- 2598942 TI - Conformation of secretin in dimethyl sulfoxide solution. NMR studies and restrained molecular dynamics. AB - The solution conformation of the 27-residue polypeptide hormone secretin in dimethyl sulfoxide has been determined on the basis of 1H-NMR measurements. The experimental data set used in the structure determination consisted of 98 nuclear Overhauser-enhancement-derived interproton and dihedral angle restraints from coupling constants. The NH-NH and H alpha-NH NOEs were determined from build-up rates, while the remaining distances were classified in a qualitative manner. The structure calculations consisted of two phases. First, dynamical simulated annealing calculations were carried out to find conformations of the peptide which satisfy NOE and phi dihedral restraints. The convergence of ten calculated structures was good except for those regions of the molecule where NOE data were not unambiguous. From the calculated set another initial structure was built which was again minimized in several 5-ps calculations now employing the full empirical energy function. The resulting structures of secretin reveal conformationally well-defined regions, but not a single uniform secondary structure. The structure is different from the calculated structure from trifluoroethanol/water measurements. PMID- 2598943 TI - Colour Doppler echocardiographic assessment of regurgitant flow in mitral valve prolapse. AB - Colour flow mapping was used to examine the pattern of regurgitant flow in 46 patients with mitral regurgitation due to mitral valve prolapse. Valve morphology was assessed from the real-time two-dimensional image and the presence of mitral regurgitation was determined from real time Doppler. On morphological criteria 11 (24%) patients had isolated or predominant anterior leaflet prolapse, 22 (48%) patients posterior and 13 (28%) patients bi-leaflet prolapse. A single regurgitant jet was detected in 43 patients (93%) and multiple jets in three (7%). The direction of the regurgitant jet was assessed in multiple views in two orthogonal planes (antero-posterior and medial-lateral) defined in relation to the mitral valve leaflets. The regurgitant jet was eccentric in the antero posterior plane of the mitral leaflets in 40 of 45 (89%) cases and in the medial lateral plane in 36 of 40 (90%) cases. Posterior leaflet prolapse was usually associated with antero-medially directed jets, anterior leaflet prolapse with postero-central or postero-lateral jets and bi-leaflet prolapse with predominantly postero-medial jets. In a subgroup of patients with significant mitral regurgitation and an eccentric regurgitant jet, a 'swirling' effect was produced with late systolic flow in the body of the left atrium toward the mitral valve. Colour flow mapping in patients with mitral regurgitation due to mitral valve prolapse demonstrated eccentric jets in most patients. The direction of regurgitant flow appeared to depend greatly on the dynamic anatomy of the mitral valve leaflets during systole. Although a single jet was detected in most patients, multiple jets did occur in a minority. PMID- 2598944 TI - Inaccuracy of various proposed electrocardiographic criteria in the diagnosis of apical myocardial infarction--a critical review. AB - The diagnostic accuracy of the standard electrocardiogram (ECG) in apical myocardial infarction (MI) was evaluated in 112 consecutive patients with recent MI and wall-motion abnormalities limited to the left ventricular (LV) apex on two dimensional echocardiography, performed at rest 21 to 84 days after MI. The following patterns of abnormal (greater than or equal to 30 ms) Q waves were found: anteroseptal (Q V1-V4) in 44 patients (39.3%), anterolateral (Q V1-V6 and/or I, aVL) in 22 (19.6%), inferior (Q III, aVF or II, III, aVF) in five (4.5%), lateral (Q I, aVL and/or V5-V6) in five (4.5%), anteroinferior in six (5.3%); non-Q MI was present in 30 patients (26.8%). By applying various proposed ECG criteria, the presence of apical MI was correctly identified in very few (24, 21%) patients. LV apex was extensively asynergic in 85 patients (76%) and partially asynergic in 27 (24%). All the patients with Q waves in lateral leads and 47% of the patients with non-Q MI had partially asynergic LV apex, while in the other ECG patterns, extensively asynergic LV apex was predominant. The presence of both greater than or equal to 30 ms Q waves and loss of R in left precordial leads and I strongly suggests extensive apical asynergy; normal QRS in the same leads, however, does not exclude extensive apical involvement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598945 TI - Ventricular fibrillation in coronary angiography: what is the role of contrast medium? AB - A retrospective review of patients with coronary angiography was undertaken to establish the incidence of ventricular fibrillation and other serious arrhythmias and to identify possible causative factors, in particular whether the use of non ionic contrast medium increased the risk of a serious arrhythmia. Out of 3660 patients reviewed there were 10 cases of ventricular fibrillation. In all cases, there were identifiable technical factors thought to have accounted for the arrhythmia. There were no cases of ventricular fibrillation complicating a technically satisfactory injection of ionic or non-ionic contrast medium. There was no significant difference in the incidence of serious arrhythmias between patients given ionic and those given non-ionic contrast medium. PMID- 2598946 TI - Haemodynamic advantage of the Valsalva manoeuvre during heavy resistance training. AB - A nuclear probe was used to assess beat-to-beat changes in relative cardiac output in eight elite athletes during isometric exercise. Three subjects underwent simultaneous intra-arterial blood pressure recording. Stroke volume fell by 68 +/- 4% during Valsalva's manoeuvre alone, but by 42 +/- 9% with simultaneous isometric handgrip. Blood pressure changes during isometric handgrip were significantly modified by simultaneous Valsalva's manoeuvre. In particular no late strain phase fall or post-strain overshoot in blood pressure was seen, hence there was no baroreceptor-mediated fall in heart rate. Maximum Valsalva's manoeuvres in athletes invoked extreme falls in cardiac output and blood pressure which were attenuated by simultaneous isometric handgrip. The mechanism of this may be twofold: increased venous tone maintains stroke volume; and/or increased arteriolar tone maintains blood pressure. PMID- 2598947 TI - Nocturnal angina in patients with fixed coronary stenosis. Increased coronary vasoconstrictive sensitivity with independence of pacing ischaemic threshold. AB - Atrial pacing and ergonovine tests were performed in 18 consecutive patients with unstable angina at rest and significant coronary artery stenosis (greater than or equal to 90% in greater than or equal to one vessel in 16 patients). 13 of them also had exertional angina. 14 patients presented at least one positive response (greater than or equal to 1.0 mm ST-segment shift) to pacing, with a heart rate (144 +/- 11 vs 75 +/- 13 beats min-1, P less than 0.001) and double product (195 +/- 26 vs 108 +/- 32 x 10(-2), P less than 0.001) significantly higher than during angina at rest. In the ten patients who presented nocturnal angina, the incidence of positive response to pacing and the pacing ischaemic threshold, tested on three different days, were similar to those seen in the remaining patients. In contrast, the ergonovine test was positive in all patients with nocturnal angina (100%), who required a low dose (0.28 +/- 0.2 mg), but it was positive in only four (50%) of those without nocturnal angina, who needed a higher dose (0.55 +/- 0.12 mg, P less than 0.005). Therefore, in patients with severe coronary stenosis and exertional angina, spontaneous episodes, including nocturnal angina, are not related to increases in heart rate. The increased coronary vasoconstrictive sensitivity found in these patients, particularly those with nocturnal angina, was not dependent on the status of the coronary reserve, which strongly suggests that changes in coronary tone, focal or diffuse, are involved in the mechanisms of these ischaemic events. PMID- 2598948 TI - Risk factors for acute myocardial infarction in Copenhagen. I: Hereditary, educational and socioeconomic factors. Copenhagen City Heart Study. AB - The Copenhagen City Heart Study was designed to evaluate the incidence of and risk factors for cardiovascular disease. Information about potential risk factors was collected from 14,223 persons during an initial examination (1976-78) (attendance rate 74%). Information about new cases of acute myocardial infarction (AMI) was obtained from a second examination (1981-83), hospital registries and death registries up to December 31st 1983. This article deals with 'basic' risk factors, namely age, sex, some factors presumably of genetic character (family history of AMI, early parental death, height and earlobe crease) and social factors such as length of school education, income and marital status. The Cox regression model was used. As expected, the risk of first AMI increased with age and was highest among males. Earlobe crease and family history of AMI were found to be significant risk factors, the relative risk being 1.4 for both. No effect was found of early parental death and height. Low grade of education was associated with a higher risk, significantly so only in women, the relative risk being 1.7. Low income carried an increased risk, particularly for females. Cohabitation carried a higher risk, most pronounced in the low income group. Approximately half the effect of education was exerted through its influence on income and marital status. PMID- 2598949 TI - Probability of a return to work after either coronary balloon dilatation or coronary bypass surgery. AB - To examine whether coronary angioplasty has a different effect on work resumption than has coronary artery bypass surgery, we studied the work status of patients before and at least 1 year after either intervention. The population consisted of men aged less than 60 years, submitted to these procedures from September 1983 to July 1984. Of the 261 eligible patients, 219 (84%) participated, 94 after an angioplasty and 125 after a bypass procedure. 6 months preceding the intervention, 52% of the men were working. This had decreased to 47% at follow up. Multiple logistic regression analysis showed that failure to resume work was correlated with bypass surgery vs balloon dilatation (rate ratio 1.8; 95% CI, 1.0 3.4), not working beforehand (rate ratio 6.5; 1.2-4.3), age greater than 55 years vs less than or equal to 50 years (rate ratio 2.6; 1.3-5.4) and with angina at follow-up (rate ratio 1.8; 1.0-3.3). Taking these additional risk factors into account permits a prediction of the probability of a return to work. PMID- 2598951 TI - Non Q-wave myocardial infarction following hyperventilation test. AB - We report a case of acute myocardial infarction following a hyperventilation test performed at coronary angiography. The potential pathophysiological mechanisms and clinical implications are discussed. PMID- 2598950 TI - Sustained-release diltiazem versus metoprolol in stable angina pectoris. AB - The efficacy of sustained-release diltiazem (diltiazem-SR) 120 mg b.i.d. was compared with metoprolol 100 mg b.i.d. in 12 patients with stable angina. Following a 1-week placebo period, patients received diltiazem-SR or metoprolol in two 3-week treatment periods, in a randomized double-blind crossover design. Total exercise time was increased more with diltiazem-SR than with metoprolol (1.2 min vs 0.4 min, P = 0.02), although the reduction in frequency of weekly anginal attacks was equal with both drugs (5 +/- 3 with placebo to 1 +/- 1 with both drugs). The difference between diltiazem-SR and metoprolol may, in part, be due to the fact that the tests were performed 12 h after drug administration. The diltiazem plasma levels were in the therapeutic range; metoprolol plasma levels, in contrast, were all below the therapeutic range. In addition, the patients might be tired out earlier during beta-blockade therapy, because a greater increase in exercise time with diltiazem-SR compared with metoprolol was found in those patients in whom the exercise endpoint changed from angina to fatigue. Thus, diltiazem-SR effectively reduces the frequency of anginal attacks when given twice daily, and improves exercise capacity to a greater extent than metoprolol 12 h after last dose. PMID- 2598952 TI - Asymptomatic congenital coronary artery aneurysm in adulthood. AB - Congenital coronary aneurysm is a rare disorder and most of the previously reported cases were necropsy findings, usually in association with other coronary artery abnormalities. Although rupture and thrombosis were the most common causes of death, the management of this condition has not been well defined. A patient with a right coronary artery aneurysm which remained stable over 8 years is described. It is suggested that the disease might be compatible with long-term survival. PMID- 2598953 TI - Per rectal thallium scintigraphy for the assessment of portosystemic shunt: an experimental study in the bile duct ligated rats. AB - Bile duct ligated rats (n = 7) have been investigated for 6 months. Two patterns of evolution have been observed: (i) progressive development of cirrhosis and portosystemic shunt (detected by 201Tl per rectal scintigraphy) in three animals, (ii) repermeabilization of the biliary tract in four animals. Despite the small number of animals investigated, the 201Tl per rectal scintigraphy seems to be a good indicator of portosystemic shunt secondary to biliary cirrhosis. PMID- 2598954 TI - Lung ventilation and perfusion scintigraphy in the follow up of repaired congenital diaphragmatic hernia. AB - To evaluate the effects of congenital diaphragmatic hernia (CDH) and pulmonary hypoplasia on subsequent lung function and development, we performed lung 133Xe ventilation and 99mTc perfusion scintigraphies in a group of infants who had undergone surgical repair of a severe left CDH with respiratory distress within the first 6 h of life. The initial lung scans performed in 15 children, 2-3 months of age, demonstrated a decreased ventilation in 7. In 9 children there was a trapping of 133Xe at the left lung base. Perfusion to the hernia side was reduced in 8 of the children. We re-evaluated 11 of these 15 patients after 1-2 years. The ventilation to the left lung was still decreased in 3, but perfusion remained decreased in 9. After 5 years, ventilation to the hernia side was normal in 4 of the 5 patients studied, whereas pulmonary blood flow was abnormal in 4. These results show a progressive improvement of ventilation with a persisting reduction of perfusion to the lung of the hernia side, suggesting a primary vascular pulmonary hypoplasia in CDH. PMID- 2598955 TI - Biodistribution of Tc-99m methoxy-isobutyl-isonitrile (MIBI) in humans. AB - Hexakis (methoxyisobutilisonitrile) technetium(I), 99mTc-MIBI, has been proposed for myocardial perfusion studies. We have evaluated the biodistribution of this new agent in normal volunteers at rest and after stress. The biodistribution of 99mTc-MIBI is characterized by rapid blood clearance and a consequently early myocardial uptake. The initial intense hepatic activity is cleared into the gallbladder at 1 h after injection, and the best target to non target ratio is observed at 60-90 min after injection. Absorbed radiation dose calculations show that the thyroid is the critical target organ (230 mRad/mCi at rest), presumably because of 99mTc-pertechnetate generated in vivo. Our results indicate that 99mTc MIBI is a promising tracer for myocardial perfusion imaging. PMID- 2598956 TI - Assessment of the binding properties of Granuloszint. AB - 123I-Granuloszint (a murine monoclonal antibody--called AK-47--against NCA-95 glycoprotein of granulocytes) has been proved to be a very convenient and successful radiopharmaceutical for visualizing infectious diseases. For a broad introduction in routine nuclear medicine it was necessary to optimize the labelling method and to determine in vitro exactly those biological and binding parameters which are relevant for an effective application in vivo. Binding to granulocytes has been shown to be specific and saturable (non specific binding about 10%) and is not via the Fc part of the antibody. The investigation of the binding properties of 125I-labelled AK-47 gave the following results: affinity constant 5 x 10(8) M-1, 20,000-200,000 epitopes per granulocyte and an immunoreactivity of more than 90%. Labelling with 123I reduced the immunoreactivity to 40%. The Lindmo method and immunoblotting are used as quality control to check the likely in vivo behaviour of the labelled antibody. There is a good correspondence between the results from the two methods. With our special labelling method and the different in vitro tests we have found a reliable way to control the production and to assure an optimal binding behaviour of 123I Granuloszint. PMID- 2598957 TI - Biodistribution of anionic separated MDP complexes from different MDP preparations. AB - The biodistributions of different Tc-MDP complexes, separated from different MDP preparations by anionic exchange chromatography, were investigated. We included MDP preparations from one producer with both ascorbic and gentisic acid as stabilizing agent and one preparation with ascorbic acid from a second producer. Bone to soft tissue ratios in rats were compared for the different Tc-MDP complexes separated. It seems that the elution profile of the radiochromatogram may indicate the biodistribution of the preparation. Ascorbic acid and gentisic acid caused different elution profiles and the different complexes isolated were demonstrated to have different bone to muscle ratios. PMID- 2598958 TI - Cholesterol enhances the delivery of liposome-encapsulated gallium-67 to tumors. AB - The effect of incorporation of cholesterol (CH) into liposome membranes on the delivery of 67Ga encapsulated in liposomes to tumors was studied. The changes of the blood clearance of liposomes, liposome stability in serum and liposome uptake by the liver and spleen were also examined. Liposomes were prepared from distearoylphosphatidylcholine with various amounts of CH. It became clear that large amounts of CH (above 33 mol%) dramatically enhanced liposomal delivery of 67Ga to sarcoma 180 solid tumor in mice. Large amounts of CH increased the liposome stability in serum and decreased liposome uptake by the liver and spleen after intravenous injection, thus prolonging the blood clearance of liposomes. These observations suggested that the large delivery of 67Ga by CH-rich liposomes resulted from the extended retention and increased amount of liposomes in the circulation, caused by the incorporation of large amounts of CH. Small amounts of CH decreased liposome stability and hastened blood clearance, but had little effect on 67Ga delivery to the tumor. CH-rich liposomes showed high tumor uptake, with high tumor to blood and tumor to tissue ratios of 67Ga. It is anticipated that 67Ga-carrying liposomes will be an excellent tumor imaging agent for clinical use, provided that a correct choice of CH content is made. PMID- 2598959 TI - Glomerular filtration rate and the kinetics of 123I-metaiodobenzylguanidine. AB - We have recently reported evidence that the calcium antagonist nifedipine can improve the tumour retention of 131I-metaidobenzylguanidine (131I-MIBG) in patients with malignant phaeochromocytoma. During studies of the pharmacological modification of tumour MIBG kinetics, it is important to distinguish clearly between a direct effect on MIBG cellular retention by a pharmaceutical, and secondary effects due, for example, to a change in glomerular filtration rate (GFR). In order to provide the fundamental kinetic data required for the numerical modelling of the effect of nifedipine on tumour MIBG kinetics, we have investigated the influence of GFR on MIBG plasma and renal kinetics. The 123I MIBG plasma curve and MIBG renal plasma clearance rate were studied in ten patients, ranging from subjects without biochemical or scintigraphic evidence of phaeochromocytoma to individuals with widely disseminated metastatic disease. GFR was measured using the 99mTc-DTPA plasma clearance method. In four cases, the studies were repeated with the patients taking oral nifedipine. Statistically significant correlations were found between GFR and the MIBG plasma concentration. MIBG renal plasma clearance rate and the early (0 to 5 min) renal excretion of MIBG. The data permit the evaluation of the plasma integral during the first few min following bolus injection, a quantity important in the numerical modelling of tumour kinetics. GFR was found to have a major influence on whole-body MIBG kinetics, but there was also evidence of the effect of the metastatic tumour burden. PMID- 2598960 TI - "Whole brain" politics and brain laterality research. AB - The paper discusses a recent international conference in Munich (FRG) on brain laterality research. An open letter on the goals of the conference is considered. In this letter, the "automatic" moral and intellectual decay of "left brain" modern society was predicted, and a clarion call for the reinsertion of "whole brain" values into our over-mechanized culture was sounded. Discussion of the conference itself focuses on the political and social risks involved in selling irrationalist ideologies - even well-meaning ones - in the name of science. The paper calls for a more responsible attitude among modern brain-laterality researchers who would participate in scientific conferences that blur the distinction between description and social prescription. PMID- 2598961 TI - Unipolar and bipolar schizoaffective disorders: a comparative study. I. Premorbid and sociodemographic features. AB - Seventy-two schizoaffective patients were investigated longitudinally (mean follow-up period 25.6 years). Unipolar (n = 37) and bipolar (n = 35) schizoaffectives were compared. Relevant differences in sociodemographic variables were found between the two groups, especially in: (a) sex distribution (more females among unipolar schizoaffectives), (b) social class, (c) occupational and educational level (higher in bipolars), and (d) premorbid personality (obsessoid and low-self-confidence personality types were more frequent in unipolars). Surprisingly there was no difference in age of onset, but some factors were identified that elevated the age of onset in bipolar and reduced it in unipolar schizoaffectives, which may explain this finding. Among bipolars there were more frequent relapses, but there was more suicidal symptomatology in unipolars. No differences were found with regard to long-term outcome, i.e. disability (Disability Assessment Schedule), level of functioning (Global Assessment Scale) or psychopathology at follow up. PMID- 2598962 TI - Unipolar and bipolar schizoaffective disorders: a comparative study. II. Long term course. AB - Seventy-two schizoaffective patients were investigated longitudinally (mean follow-up period 25.6 years). Of these, 37 were classified as unipolar and 35 as bipolar schizoaffectives. Their long-term courses were compared. Bipolar schizoaffectives were found to have shorter cycles, i.e. more frequent relapses and more episodes. Bipolars displayed much more variation in symptomatology. Unipolar schizo-affectives had longer periods of remission (that is the last relapse-free period if longer than 3 years) and more frequently showed suicidal symptomatology than did bipolar schizoaffectives. Altogether bipolar schizoaffective disorders had a more unfavourable course than unipolar disorders. PMID- 2598963 TI - Unipolar and bipolar schizoaffective disorders: a comparative study. III. Long term outcome. AB - Seventy-two schizoaffective patients were investigated longitudinally (mean follow-up period 25.6 years). Long-term outcome of unipolar (N = 37) and bipolar (N = 35) schizoaffectives was compared. Different aspects of outcome were investigated separately using standardized instruments of evaluation. No differences were found between unipolar and bipolar schizoaffective patients with regard to global functioning (GAS), disability (WHO/DAS) or psychopathological symptomatology at follow-up. There were also no differences in social consequences of the illness, i.e. downward occupational and downward social drift, premature retirement and achievement of the expected social development. PMID- 2598965 TI - Psychomotor disturbances in psychiatric patients as a possible basis for new attempts at differential diagnosis and therapy. IV. Brain dysfunction during motor activation measured by EEG mapping. AB - In parts I-III of this series psychometric evidence was reported of a "psychotic motor syndrome" (PMS) in schizophrenic and endogenous depressed patients, which was not found in non-endogenous depressed or healthy persons. An attempt is reported to establish signs of brain dysfunction in these patient groups during motor activation, using a 16-channel EEG mapping system. "Resting" conditions after a special relaxation procedure were compared with simple and complex motor tasks (and music perception/reproduction; to be reported separately). Two measurements, at least 2 weeks apart, were obtained for each subject, in order to obtain information on the influence of drug treatment and/or psychopathological improvement on brain dysfunction. In all, 23 male and 25 female schizophrenics, 11 male and 18 female non-endogenous depressed patients (not actually mediated, i.e. drug naive or wash-out period of 1 week to 17 years), and 26 male and 37 female endogenous depressed patients (medicated with tri- or tetracyclic antidepressants and/or benzodiazepines; no lithium treatment) were compared with 22 male and 17 female control persons (i.e. total n = 179). Major findings were obtained in the delta and alpha frequency bands yielding signs of "diffuse hyperactivation" in schizophrenic and endogenous depressed patients as compared with the patterns found in healthy persons. However, since in the non-endogenous patients a (less marked) hyperactivation of various EEG parameters was also found, unspecific effects such as anxiety/arousal may have influenced the results in psychotic patients, which was to be explored further. Drug treatment tended to "normalize" the activation pattern both in schizophrenics and endogenous depressed patients. Viewing the findings on schizophrenics using neuroimaging methods [single photon emission computerized tomography-(SPECT), magnetic resonance imaging-(MRI), positron emission tomography-(PET)], these results suggest pathological brain organization connected to an impaired motor performance (evident peripherally as PMS) in schizophrenic and endogenous depressed patients. If it is possible to further "externally validate" (by SPECT/MRI/PET) EEG mapping data this method may exclusively offer the possibility of innocuous long-term follow up of brain dysfunction in psychotic patients ("brain function monitoring"). This could enable the early recognition (and early therapy) of negative symptoms. Finally, the EEG mapping findings provide further neurophysiological basis for the use of motor training programs in the additional therapy of psychiatric patients. PMID- 2598964 TI - Foix-Chavany-Marie-syndrome--neurological, neuropsychological, CT, MRI, and SPECT findings in a case progressive for more than 10 years. AB - In a 66-year-old woman signs and symptoms of bilateral opercular syndrome (Foix Chavany-Marie-syndrome) developed progressively over a period of more than 10 years. Facio-linguo-velopharyngeo-masticatory diplegia with automatic-voluntary dissociation was accompanied by motor aphasia and oral apraxia leading to a state of almost complete anarthria. Although it initially resembled the anterior biopercular syndrome there are also features indicating involvement of the posterior opercula. Although the aetiology remains obscure without pathological data, a bilateral focal brain atrophy is assumed. This is probably the first case documented by MRI and SPECT. PMID- 2598966 TI - Schizophrenia--a disease of young single males? Preliminary results from an investigation on a representative cohort admitted to hospital for the first time. AB - The later age at onset of schizophrenia in females, reported in the literature, led to a study of transnational case register data and of a cohort of all patients admitted to hospital for the first time with a non-affective functional psychosis from a defined catchment area. The preliminary analysis of the first representative sample of 86 patients showed that at the time of first admission with a diagnosis of schizophrenia (according to different diagnostic definitions) as well as at the time of onset of the disease (operationalized on different levels) females were on average 5 years older than males. Singles, and even more so young single males, were clearly overrepresented among those first hospitalized in comparison to the population of the same age. To remain single seems to be in most cases a consequence of the disease or of premorbid characteristics in those predisposed to schizophrenia. PMID- 2598967 TI - Coping with symptoms of relapse in schizophrenia. AB - A pilot study is reported of 30 chronic schizophrenic patients at the psychiatric out-patient facility of Government General Hospital, Madras, India. The objectives of the study were to assess the patients' perception of prodromata of relapse and their coping mechanisms. Patients were questioned on these aspects, using a semi-structured interview guide. The study showed a high degree of perception of prodromal signs amongst the cohort. Only 4 patients were unable to perceive any prodromata of relapse. Most commonly noted prodromal symptoms were disturbed sleep and slowness and underactivity. Patients had also resorted to various coping measures such as internal dialogue and talking to a close relative or friend. The study has clearly proved that Indian schizophrenic patients are perceptive of prodromata of relapse and developed self-help methods. These methods, if properly identified, could be incorporated in psychosocial intervention programmes. PMID- 2598968 TI - Effect of short-term omeprazole administration on serum pepsinogens in relation to fasting serum gastrin and gastric acid secretion. AB - A study has been done in 10 male healthy volunteers of the effect of oral omeprazole 20 mg daily for 3 days on the serum concentrations of Pepsinogens A and C in relation to changes in fasting serum gastrin and basal and pentagastrin stimulated gastric acid output. The concentrations of Pepsinogens A and C showed concomitant and variable but significant increases, and the Pepsinogen A, C ratio did not change during the 3-day course of omeprazole. The increments were also significantly correlated with the increase in fasting serum gastrin and with the reduction in pentagastrin stimulated acid output. The correlations were mainly due to the marked inhibition of gastric acid secretion and the corresponding increases in serum gastrin and Pepsinogens A and C in two subjects, as in the other 8 subjects the changes were only modest. There appears to be a relationship, therefore, between the degree of inhibition of acid by omeprazole and the parallel increases in both serum pepsinogens and fasting gastrin. PMID- 2598969 TI - The effect of ageing on the pharmacokinetics of dihydrocodeine. AB - Although poor renal function reduces clearance of dihydrocodeine in man, and renal impairment occurs with ageing, no significant differences occurred in the handling of single doses of dihydrocodeine between elderly patients and young, normal subjects. After multiple dosing, the maximum concentration was significantly different between the groups, being higher in the elderly. The increase in the area under the curve in the elderly was 25% greater than in the young on chronic therapy. This difference was not statistically significant, but was likely to be of clinical significance. The elderly patients' mean creatinine clearance (61.8 ml per min) was significantly lower than that in the young (137 ml per min), and there was a significant correlation between the half-life at single dosing and the blood urea concentration. Variability in all measurements was marked in both groups, and hence no clear guidelines can be given on therapeutic dosing. The small initial dose with alterations thereafter depending on clinical effect is the best advice. PMID- 2598970 TI - Simultaneous study of the pharmacokinetics of intravenous and oral nicardipine using a stable isotope. AB - The systemic elimination of nicardipine has been studied by an initial oral administration of nicardipine followed 1.25 h later by intravenous injection of the deuterium-labelled molecule (D3 nicardipine). To check that intravenous kinetics was not modified by the oral administration, an i.v. injection of unlabelled nicardipine (D0 nicardipine) was also given. The study was carried out in six healthy male volunteers, aged between 24 and 27 years, according to a Latin square cross-over design. Similar values were found for each kinetic parameter after i.v. administration regardless of whether it was administered alone by that route or with an oral dose. The plasma level-time curves of nicardipine were described by a three open compartment model. The total plasma clearance was about 800 ml/min, the volume of distribution was of the order of 1 l/kg and the half-life of beta-elimination ranged from 4 to 5 h. The elimination rate constant beta was independent of the route of administration. PMID- 2598971 TI - Pharmacokinetics of intravenous salbutamol in renal insufficiency and its biological effects. AB - Salbutamol was administered intravenously to 5 patients with renal function impairment for estimation its pharmacokinetic parameters. The mean terminal half life was 256 min, similar to previously reported values in healthy adults. The mean clearance (167 ml/min) and the mean volume of distribution (551) were decreased. These parameters were not correlated with the creatinine clearance. A slight but significant decrease was observed in the plasma potassium level up to 125 min after the salbutamol infusion. The heart rate was significantly increased, and the increase in 3 patients was correlated with the salbutamol concentration. The biological effects of the drug were less marked than expected. PMID- 2598972 TI - Acetylator polymorphism in Parkinson's disease. AB - Acetylator phenotype has been determined using sulphamethazine in 100 patients with Parkinson's disease and in 93 age-matched normal control subjects. Sixty nine patients and 54 control subjects were classified as slow acetylators (NS). No relation was found among acetylator polymorphism and age at onset or clinical stage of disease. Amongst slow acetylators, the percentage of acetylated sulphamethazine in plasma was significantly lower in patients than in controls. Despite this finding, the results do not support any relationship between acetylator polymorphism and the risk of developing Parkinson's disease. PMID- 2598973 TI - Effect of exercise on met-enkephalin in unfit and superfit individuals. AB - Twenty-four unfit volunteers and twenty-three superfit athletes were subjected to a progressive intensity treadmill exercise to total exhaustion in order to study the plasma met-enkephalin response to exercise. Blood samples were collected before and 5 min post-exercise. The basal met-enkephalin levels were significantly higher in the superfit individuals (180 fmol.ml-1) than in the unfit individuals (126 fmol.ml-1). Post-exercise the increase from basal levels of plasma met-enkephalin was significantly higher in the superfit athletes (180 278 fmol.ml-1) than in the unfit individuals (126-157 fmol.ml-1). The magnitude of the met-enkephalin responses to exercise therefore appears to be dependent on the amount of work performed and the degree of previous physical training. Peripherally circulating opioid peptides may, therefore, possibly play a role in the body's adaptation to exercise training. PMID- 2598974 TI - Serum digoxin and beta-methyldigoxin in elderly patients on hospital admission: correlation with home compliance and clinical variables. AB - Serum digoxin and beta-methyldigoxin (BMD) were measured in 165 elderly patients (age greater than 60 years) admitted to hospital, of whom 109 had been treated at home with digoxin and 56 with BMD. The mean BMD level was significantly lower than that of digoxin (1.1 vs. 1.4 ng/ml). Creatinine clearance and daily dose were the variables most strongly associated with digoxin level, and the prescribed dose and serum albumin were the best predictors of the BMD concentration. Compliance was assessed by a compliance index (CI), namely the ratio of the measured glycoside concentration, corrected for creatinine clearance, over the expected steady-state dose, calculated from a hospitalized reference group. Compliant individuals in both treatment groups, i.e. those with a CI greater than the median value, were characterized by a lower daily dose and dosage frequency. Toxicity, whether clinical or electrocardiographic, was present in 9% of the patients and was associated only with a significantly higher mean serum level of the drug. PMID- 2598975 TI - Effects on cimetidine bioavailability of metoclopramide and antacids given two hours apart. AB - Plasma cimetidine levels were determined in 9 normal subjects after a single oral dose of cimetidine 400 mg under control conditions, 2 h before metoclopramide 20 mg and 2 h after a potent antacid. The bioavailability of cimetidine was not significantly affected by metoclopramide and it was marginally reduced by the antacid. PMID- 2598976 TI - Cisapride and gastric emptying of a solid meal in dyspeptic diabetics without autonomic neuropathy and in healthy volunteers. AB - Gastric emptying was studied in 10 insulin-treated, long-standing, diabetic out patients with upper gastrointestinal, dyspeptic symptoms. Autonomic neuropathy, mucosal lesions and chloropeptic hyposecretion were excluded. Gastric emptying of a labelled solid meal (99mTc-sulphur colloid-infiltrated chicken liver) was clearly delayed by comparison with normal subjects: the mean gastric emptying half-time was almost 5-times longer (245.6 vs 52.5 min), and the gastric emptying rate at 120 min was 75% slower. Cisapride 10 mg i.v. significantly accelerated both parameters, and placebo had no effect upon them. In conclusion, gastroparesis may be present in diabetics without autonomic neuropathy, and cisapride may improve gastric emptying in such patients. PMID- 2598977 TI - Bioavailability of suckable tablets of oral N-acetylcysteine in man. AB - The pharmacokinetics and bioavailability of suckable tablets and granules of N acetylcysteine (NAC) have been compared after oral administration of 400 mg doses to 10 healthy volunteers. The oral bioavailability of the NAC tablets was 103%. In a multiple dosing study of the same tablets in the same subjects, a high maintenance plasma level of NAC was revealed. PMID- 2598978 TI - Effect of food on the absorption and pharmacokinetics of prednisolone from enteric-coated tablets. AB - Prednisolone absorption and bioavailability of 10 mg enteric-coated (EC) and plain (uncoated) tablets were investigated after fasting and heavy meals (EC only) consumed to satiety in normal healthy volunteers. The same volunteers had also received 16 mg of prednisolone intravenously. In fasted subjects, the absolute bioavailability fraction, as normalised for intravenous doses, of prednisolone from plain tablets was 1.055 and from EC tablets was 0.996. The peak concentrations after plain and EC tablets were 309 and 249 ng/ml attained at 0.98 and 5.14 h, respectively. The means plasma elimination half-lives following the plain, EC tablets and intravenous administration in fasting conditions were 3.73, 3.89 and 3.78 h, respectively. Food interfered with both the absorption and the pharmacokinetics of prednisolone after EC tablets resulting in variability in its plasma levels. In some cases absorption of prednisolone was delayed for 12 h and remained at a measurable level for 24 h. In other cases, a normal absorption pattern was observed. This inter- and intrasubject variability of the effect of food appears to be related to its quantity, constituents and also the subjects physiological characteristics. It is concluded that enteric-coated prednisolone tablets should be administered at least 2 h between meals. However, for more predictable corticosteroid absorption (perhaps thus avoiding the therapeutic failure), plain prednisolone tablets are preferable. PMID- 2598979 TI - Nasal administration of glucagon and human calcitonin to healthy subjects: a comparison of powders and spray solutions and of different enhancing agents. AB - The systemic availability of glucagon and human calcitonin given intranasally to healthy volunteers as spray solutions or powders has been examined. Glucagon was absorbed only when surfactants were used, and 9-lauryl ether (as a spray) and sodium glycocholate (as spray or powder) were equally active. Calcitonin was poorly absorbed when given alone but the surfactants dihydrofusinate (as spray or powder) and glycocholate (as a spray) were equally active in promoting absorption. Thus, enhancers are required to obtain significant nasal absorption of glucagon and calcitonin and powders and spray solutions did not differ in terms of systemic availability. PMID- 2598980 TI - Is addition of prazosin beneficial in chronic heart failure refractory to angiotensin converting enzyme inhibition? PMID- 2598981 TI - The regulation of medicines post 1992. AB - The European Community (EC) is scheduled to become a fully integrated market by 1992. Currently the present national variations in pharmaceutical marketing authorization constitutes an unresolved barrier. The need is for agreed and clearly specified requirements to afford EC wide marketing authorization within agreed time frames. Great care will be required to avoid such problems as a European drug-lag and mounting cost, to the detriment of patients, government, and the research-based pharmaceutical industry. PMID- 2598982 TI - Comparison of haemodynamic effects of nifedipine and molsidomine in patients with coronary artery disease. AB - The haemodynamic effects of oral nifedipine 20 mg and molsidomine 4 mg were compared in 24 patients with coronary artery disease. Molsidomine unlike nifedipine caused a significant fall in mean pulmonary artery pressure and left ventricular end-diastolic pressure. Both drugs caused a significant and comparable reduction in systolic and diastolic blood pressure. Although only nifedipine significantly reduced systemic vascular resistance the difference between the drugs was not significant. The heart rate was significantly increased by nifedipine but not by molsidomine. The ejection phase indices were all increased by molsidomine and the increment in the mean normalized systolic ejection rate was significantly greater than that due to nifedipine. The left ventricular end-systolic volume index decreased significantly after molsidomine but not nifedipine. Neither drug significantly affected left ventricular end diastolic volume index, stroke volume index, maximal rate of rise of left ventricular pressure or left ventricular stroke work index. PMID- 2598983 TI - The effects of intravenous and oral nifedipine on ex vivo platelet function. AB - We have studied the possible anti-platelet effects of an intravenous formulation of nifedipine (0.75 mg as a bolus and an infusion of 1.2 mg.h-1 for 2 h), or equivalent volumes of the vehicle alone, or normal saline, in a double-blind crossover fashion in six healthy subjects. The effects of a standard oral formulation (20 mg sustained-release) compared to identical placebo were also studied in twelve other subjects. Platelet function was assessed by the addition of collagen, adenosine diphosphate, or adrenaline to whole blood followed by single platelet counting. Intravenous nifedipine had no effect on aggregation in response to any of the agonists, but oral nifedipine reduced aggregation caused by collagen by approximately 15%, despite similar plasma nifedipine concentrations after both formulations (18.5 ng.ml-1 after intravenous and 21.5 ng.ml-1 after oral administration). The lack of effect of intravenous nifedipine may be due to endothelial irritation caused by the vehicle. Intravenous nifedipine is unlikely to have a useful anti-platelet effect in patients who have acute coronary insufficiency. PMID- 2598984 TI - Haemodynamic effects and pharmacokinetics of felodipine at rest and during exercise in hypertensive patients treated with metoprolol or atenolol. AB - A study has been performed in thirteen patients with essential hypertension, WHO Class I-II, and a diastolic blood pressure greater than or equal to 95 mmHg, on beta-blocker (metoprolol or atenolol) monotherapy, who were also given felodipine 10 mg b.d. for 28 days. The acute and steady state blood pressure response at rest and during exercise, and the pharmacokinetics of felodipine and metoprolol, were examined. Felodipine in combination with the beta-blocker reduced the systolic and diastolic blood pressures acutely and at steady-state. The duration of the effect was longer at steady-state. There was a significant correlation between the plasma concentration of felodipine and the change in blood pressure. The increase in systolic blood pressure during exercise was of the same magnitude before and after felodipine administration. No change in resting supine heart rate was found after the administration of felodipine. There was no significant differences in the pharmacokinetics of felodipine during long-term treatment, except for the trough plasma concentration, which was increased at steady-state, even though cumulation of felodipine and its metabolite did not occur. There was a significant decrease in the maximal plasma concentration and AUC of metoprolol after 28 days of treatment with felodipine, but its elimination half-life was not changed. The adverse reactions reported during this study were those generally seen after dihydropyridines and, except for two patients who were withdrawn after the first study day, the effects were well tolerated. PMID- 2598985 TI - CI-924 effects on plasma lipids in patients with type II and type IV hyperlipoproteinaemia. AB - CI-924 (CI), 5,5'-[[1,1'-biphenyl]-2,5-diylbis(oxy)]bis[2,2- dimethylpentanoic acid] is chemically similar to gemfibrozil. Patients with Type II (n = 13) and Type IV (n = 22) hyperlipoproteinaemia (HLP) were maintained 12 weeks on a baseline diet containing 55% sugar, 15% protein 30% fat and less than 300 mg cholesterol daily to stabilize weight and lipids. They were then entered in a parallel group double-blinded protocol and received 0, 300, 600, or 1200 mg CI p.o. daily for 12 weeks. CI consistently elevated anti-atherogenic HDL and lowered VLDL at 600 mg/day in both Type II and Type IV HPL at 8 weeks. In Type II patients, CI lowered cholesterol, decreased LDL/HDL and increased ApoA-I. In Type IV patients, CI also lowered TC while elevating LDL and ApoA-II. CI had no effect on Apo-B, LDL-ApoB, or Apo-E. PMID- 2598986 TI - Inhibition of caerulein-induced gall bladder emptying by cimetropium bromide in humans. AB - The effect of cimetropium bromide, a new potent antimuscarinic compound, on caerulein-induced gall bladder emptying in 8 male volunteers was studied by real time ultrasonography. During saline infusion, caerulein (10-40 ng.kg-1.h-1) induced dose-dependent emptying of the gall bladder. There was a significant linear correlation between the dose of the peptide and the reduction in gall bladder size. A continuous infusion of cimetropium bromide (5 mg.h-1) significantly inhibited the contracting effect of caerulein on the human gall bladder, by 74% in response to the lowest dose and by 45% and 22%, respectively, to the two higher doses. The data confirm that the contracting effect of CCK-like peptides on the human gall bladder is at least partly cholinergically mediated, and they demonstrate the relaxing activity of cimetropium previously shown in animals. Provided its antispasmodic activity is also evident in disease, cimetropium should be regarded as a potentially useful agent for the treatment of biliary colic and spasm of the biliary tree. PMID- 2598987 TI - Almitrine bismesylate disposition in the human digestive tract. AB - The absorption of almitrine from the upper gastrointestinal tract has been evaluated in 6 healthy volunteers by an intubation technique. Almitrine bismesylate dissolved in malic acid was introduced into the stomach after homogenization with a meal containing the marker 14C-polyethylene glycol (PEG) 4000. Unlabeled PEG 4000 was infused into the second part of duodenum throughout the experiment. Samples of the luminal content were collected every 15 min for four hours from the stomach and at the ligament of Treitz. Blood was also collected. Almitrine was neither absorbed from nor metabolized in the stomach. About 37% of the quantity of drug emptied from the stomach was absorbed from the duodenum. Almitrine was detected in plasma 50 min after ingestion of the meal and its plasma concentration-time profile reflected the cumulative gastric emptying rate. The metabolite tetrahydroxy almitrine was found in intestinal samples as soon as unchanged drug was detected in plasma. The intraluminal rate of formation of the metabolite increased with time. The results suggest hepatic metabolism of almitrine followed by rapid excretion of the metabolite in the bile. PMID- 2598989 TI - The disposition and kinetics of intravenous N-acetylcysteine in patients with paracetamol overdosage. AB - Seventeen patients received standard treatment with intravenous N-acetylcysteine for 18 episodes of severe poisoning with paracetamol (acetaminophen). The dose of N-acetylcysteine was 150 mg/kg given in 15 min followed by 50 mg/kg in 4 h and 100 mg/kg over the next 16 h. Liver damage was absent or mild on 13 occasions (ALT greater than 500 mu/l) and severe on 5 (ALT less than 1000 mu/l). Total plasma N-acetylcysteine was estimated by HPLC. The mean maximum plasma concentration after the initial loading dose was 554 mg/l. Concentrations then fell rapidly and after 12 h a mean steady-state level of about 35 mg/l was maintained. When the infusion was discontinued N-acetylcysteine disappeared with a half-life of 5.7 h. The mean steady-state volume of distribution, AUC, mean residence time and total clearance were 536 ml/kg, 1748 mg.h.l-1, 2.91 h and 3.18 ml.min-1.kg-1. These values are generally consistent with those previously reported with much smaller doses and the disposition of N-acetylcysteine does not appear to be dose-dependent. The elimination of N-acetylcysteine was not impaired in the patients with severe liver damage, and the pharmacokinetic variables and plasma concentrations were similar in patients with and without hepatotoxicity. The dosage schedule for intravenous N-acetylcysteine should probably be modified since adverse reactions invariably occur early when plasma concentrations are at their highest, and liver damage was prevented just as effectively at the lowest as at the highest Cmax. High initial concentrations of N-acetylcysteine can be avoided with simple alternative regimens based on the kinetic data of this study. PMID- 2598988 TI - Haemodynamics as a determinant of the pharmacokinetics of and the plasma catecholamine responses to isoprenaline. AB - The total body clearance and fractional extraction of isoprenaline (ISO) have been determined, and the relation between these parameters and cardiac output established. Whether desipramine, an inhibitor of neuronal uptake, altered the plasma catecholamine response to ISO was also investigated. Seven healthy subjects were given i.v., infusions of ISO in two, consecutive 25-min periods, at constant dose rates of 31-43 and 80-124 pmol.kg-1.min-1, respectively. The total body (ER), pulmonary (ERp) and forearm (ERf) fractional extractions and the total body clearance (CL) of ISO were obtained from measurements of cardiac output and the steady-state ISO concentration in mixed central venous, arterial and forearm venous plasma. ISO-induced increases in cardiac output resulted in increases in CL, decreases in ER and no consistent change in ERf. ERp did not differ from zero. ISO also produced a dose-dependent increase in the mixed venous plasma concentrations of noradrenaline and 3,4-dihydroxyphenylglycol (DOPEG), and a decrease in that of adrenaline. Pretreatment with desipramine did not alter any of the pharmacokinetic parameters of ISO. Desipramine, however, reduced the mixed venous baseline plasma levels of noradrenaline (47%) and DOPEG (40%), and tended to reduce that of adrenaline (34%). It enhanced the plasma noradrenaline response 2.4-fold, abolished the plasma DOPEG response and did not alter the plasma adrenaline response to ISO. Hence, owing to its haemodynamic effects, ISO modifies its own pharmacokinetics which involve non-neuronal removal processes only. The increased DOPEG in plasma resulting from the ISO-induced increase in noradrenaline release was presynaptic in origin. Desipramine appears to reduce sympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2598990 TI - Application of a radioreceptor assay in a pharmacokinetic study of oxitropium bromide in healthy volunteers after single i.v., oral and inhalation doses. AB - Oxitropium bromide (OXBR) is a new anticholinergic drug, which is expected to be useful in the treatment of nocturnal asthma. The only pharmacokinetic data were obtained with the 14C-labelled compound. A sensitive radioreceptor assay for the determination of unlabelled OXBR in plasma was developed, based on competition between OXBR and 3H-N-methylscopolamine for binding to muscarinic receptors. OXBR was isolated from plasma by ion-pair extraction and re-extraction. Active metabolites present in significant amounts might interfere in the assay, but this was not the case for OXBR metabolites. Detection limits were 300 pg.ml-1 and 3 ng.ml-1 for plasma and urine, respectively. For the latter no extraction step was required. The single dose pharmacokinetics of OXBR was studied following inhalation (3 mg), oral (2 mg) and i.v. (1 mg) administration to 12 men, following an open, cross-over design. After i.v. administration the kinetic parameters were: Vc 38.41; t1/2 alpha 5.3 min; t1/2 beta 142 min; AUC 8.9 h.ng.ml 1; renal excretion 50.2%, k10 3.5 l.h-1 and total clearance 1874 ml/min. The apparent bioavailabilities were 0.48% and 12.4% by the oral and inhalation routes, respectively, based on the cumulative renal excretion. There were moderate adverse reactions due to the anticholinergic properties of the drug. PMID- 2598991 TI - Computer analysis of saccadic eye movements: assessment of two different carbamazepine formulations. AB - The central effects of two different formulations of Carbamazepine (CBZ) have been examined by analysis of saccadic eye movements (SEM) in 6 healthy volunteers, who took part in a double-blind, latin-square, placebo controlled study. Both a conventional- and a controlled-release formulation of CBZ produced a significant effect on peak saccadic velocity and saccade accuracy, but only the former affected saccade latency. Computer analysis of SEM confirmed it to be a highly sensitive method for detection of subclinical drug effects on the CNS. PMID- 2598992 TI - Changes in muscle blood flow after smoking a cigarette determined by a new noninvasive method. AB - In 9 healthy subjects the effect of smoking one cigarette (nicotine content 0.9 mg) on blood pressure, heart rate and total and muscle blood flow in the forearm was measured. Blood flow was measured by a new noninvasive plethysmographic method that simultaneously gives quantitative data about total and muscle blood flow. Smoking the cigarette did not significantly affect blood pressure or heart rate. Total blood flow in the forearm did not change but the flow to the muscle was increased and resistance in this vascular bed was decreased. The pattern of haemodynamic changes in the forearm indicates that epinephrine may be the mediator of the circulatory effects of nicotine. PMID- 2598993 TI - Determination of acetylator phenotype in Caucasians with caffeine. AB - Acetylator status in 595 healthy Caucasian volunteers was determined with caffeine. The test group consisted of 372 males and 223 females, 18 to 78 years of age. 312 volunteers were smokers. Caffeine was taken orally as Coffein Comprette (200 mg caffeine x H2O) and urine was collected for 8 h. The metabolic ratio (MR) of 5-acetylamino-6-formylamino-1-methyluracil (AFMU) to 1 methylxanthine (MX) was determined by HPLC. In total 61.7% of the group had a MR less than 0.48 and were classified as slow acetylators. MR varied from 0.01 to 0.47 in the slow acetylators and from 0.48 to 4.7 in the fast acetylator group. Clear dependence of acetylator type upon age, sex or smoking behaviour was not observed. The present study has confirmed the caffeine test as a feasible tool to determine acetylation capacity. PMID- 2598995 TI - Identification by GC/MS of 6-monoacetylmorphine as an indicator of heroin abuse. AB - A capillary gas chromatography mass spectrometry assay has been developed for the determination of 6-monoacetylmorphine in human urine, which is a confirmatory marker of heroin abuse. It was extracted with chloroform-isopropanol-n-heptane (50:17:33, v/v) from alkalinized samples (pH 9.2), using levallorphan as the internal standard. After derivatization with trifluoroacetic anhydride, the drugs were separated on a 25-m capillary column BP 10 and detected by selected ion monitoring. PMID- 2598994 TI - Hypotensive and peripheral vascular effects in healthy volunteers of repeated oral administration of pinacidil. AB - The hypotensive and peripheral vascular effects of two different oral formulations of pinacidil were investigated in twelve healthy male volunteers. Arterial blood pressure, heart rate and calf blood flow were measured on Days 1 and 7. The vasodilator activity of both formulations was confirmed by a significant increase in calf blood flow on both days, which was correlated with a significant decrease in diastolic blood pressure. There was no differences between the tablet and the pellet. PMID- 2598996 TI - Absorption and elimination of bismuth from oral doses of tripotassium dicitrato bismuthate. AB - The pharmacokinetics of bismuth subcitrate were studied in plasma and urine under conditions of single and multiple dosing (28-56 days) using atomic absorption technique. Single dose plasma pharmacokinetics showed peak concentrations of 5.5 57.5 micrograms.l-1 (mean = 24.7 micrograms.l-1), reached between 30 and 60 min post dosing with an apparent biphasic elimination pattern. Multiple dose studies showed a continuing rise in plasma concentration and urine excretion rate reaching apparent steady-state levels over 7-29 days (mean = 18 days). Washout studies in 6 individuals reciprocated accumulation. Maximum equilibrated plasma levels of 7.6-58.3 micrograms.l-1 (mean = 38.3 micrograms.l-1) were well below those associated with encephalopathy. The half-life of bismuth elimination was 20.7 days. Present patterns of intermittent dosing with bismuth are unlikely to be associated with bismuth accumulation despite slow accumulation and elimination. PMID- 2598997 TI - Absence of morphine glucuronidation in the human lung. PMID- 2598998 TI - Epidemiology of antimalarial-induced pruritus in Africans. PMID- 2598999 TI - The role of glycosphingolipids in natural immunity. Gangliosides modulate the cytotoxicity of natural killer cells. AB - Incubation of gangliosides with natural killer (NK) cells from various sources was found to inhibit NK activity in vitro whereas incubation of the same gangliosides with human or mouse lymphoma cells prior to their exposure to NK effectors resulted in a sharp increase in the NK sensitivity of the tumor cells. These effects depended on the oligosaccharide structure of the gangliosides and on the origin of the NK effector cells. The lysis of YAC cells by mouse splenocytes or of MOLT-4 cells by NK cells isolated from the peripheral blood of Syrian hamsters or humans was inhibited most strongly by pre-incubation of the effector cells with gangliosides GM3 and GD3 which are known to be elevated in the serum of tumor-bearing hosts. It is suggested that target cell-associated gangliosides may function as target structures recognized by NK cells while serum gangliosides may contribute to the inhibition of NK cells during tumor development and thus help the tumor to escape NK surveillance. PMID- 2599000 TI - Combinations of interleukins 2, 4 and 5 regulate the secretion of murine immunoglobulin isotypes. AB - Immunoglobulin (Ig) production by lipopolysaccharide (LPS)-stimulated cells in the presence of various combinations of interleukin (IL)2, IL4 and IL5 was examined. IgG1, IgM and IgE secretion was studied using a 3T3-fibroblast filler cell-supported B cell culture system, either at low cell density to support maximal Ig secretion, or at limiting dilution to determine isotype-specific precursor frequencies. In the presence of optimal concentrations of IL5 (2%) and IL2 (3 U/ml), the addition of 1 U/ml of IL4 resulted in the production of 4 ng of IgG1 per input B cell. In contrast, 1000 U/ml of IL4 alone was required to produce equivalent levels of IgG1. IL5 and IL2 increased both the precursor frequency and the amount of IgG1 secreted per clone in the presence of low levels of IL4. On the other hand, IgM secretion was decreased 10-fold by the addition of 10 U/ml IL4 or greater. This was not seen when IL5 was present. The IgM-secreting precursor frequency was unaffected by any of the lymphokines, either singly or in combination. The inhibition of IgM production and subsequent relief of this with IL5 was shown to affect the amount of IgM secreted per clone. IgE secretion was shown to be highly IL4 dependent with only minor reduction in the required concentration following addition of IL5 and IL2. At the clonal level, the majority of IgE-secreting clones (93%) at high IL4 concentrations (200 U/ml) arose from precursors which were able to produce IgM and IgG1. Furthermore, only 3% of the clones secreted IgG1 alone, with a further 3% secreting IgE alone. These results suggest that B cells in vivo are predominantly uncommitted in terms of isotype to be produced, the choice of isotype secreted being dependent on the nature of the stimulus. Overall, this work shows that the isotype secreted by B cells can be regulated using combinations of IL2, IL4 and IL5, and that major effects can be achieved by very small quantities of lymphokines acting in synergy. PMID- 2599001 TI - Syngeneic preference manifested by thymic stroma during development of thymocytes from bone marrow cells. AB - The question whether major histocompatibility complex (MHC) recognition is expressed in interactions between thymocyte progenitors and thymic stroma cells was investigated in an organ culture system, in which inductive interactions between thymic stroma cells and thymocyte progenitors of different MHC haplotypes could be measured. Thymocyte-depleted fetal thymuses were reconstituted with mixtures of syngeneic and allogeneic bone marrow cells, which also differed in their Thy-1 allele. The relative repopulating ability of the cells was estimated by determining the percentage of emerging Thy-1.1+ vs. Thy-1.2+ thymocytes. Similar values of Thy-1+ cells of the bone marrow donor type developed when the thymus were reconstituted by bone marrow from donors which were either syngeneic or allogeneic to the thymic explants. However, when a 1:1 mixture of syngeneic and allogeneic cells was applied to the thymus, a syngeneic preference was manifested in development of Thy-1+ cells. When mixtures of bone marrow cells from C57BL/Ka (Thy-1.1) and B10.A MHC-congenic (Thy-1.2) mice were used, this developmental preference was found to map to the I-E region. Thymocytes derived from bone marrow cells allogeneic to the stroma, seeded on their own, manifested an advantage over allogeneic bone marrow cells from a different MHC haplotype, in a secondary reconstitution. This suggested that allogeneic bone marrow progenitor cells can be "educated" by the host thymic stroma to behave, in the competitive reconstitution, like syngeneic cells. PMID- 2599002 TI - Differential effect of the autoimmune Yaa and lpr genes on the acceleration of lupus-like syndrome in MRL/MpJ mice. AB - The Yaa gene (Y chromosome-linked autoimmune acceleration), linked to the BXSB/MpJ Y chromosome, and the autosomal recessive lpr (lymphoproliferation) gene have been shown to accelerate the progression of the lupus-like autoimmune syndrome in the BXSB and MRL strains, respectively. To compare more directly the role of the Yaa and lpr genes in the development of the autoimmune syndrome, the Y chromosome of BXSB mice was transferred to MRL mice by backcross procedures, and the effect of the Yaa gene on the autoantibody formation and the development of lupus-like nephritis in MRL mice was investigated in comparison with those bearing the lpr mutation. The Yaa gene as well as the lpr gene were able to shorten the life span of MRL mice as a result of the accelerated development of lethal lupus-like nephritis. However, the acceleration promoted by the Yaa gene (50% mortality rate: 12 months) was less severe than that induced by the lpr gene (50% mortality rate: 7 months). This may be related to the finding that the lpr gene enhanced the production of a large spectrum of autoantibodies, including anti-DNA, rheumatoid factors and anti-gp70, and of cryoglobulins, whereas only anti-gp70 production among the autoantibodies studies was markedly enhanced by the Yaa gene. The selective autoimmune accelerating effect of the Yaa gene was similarly observed in (NZW X MRL)F1 hybrid mice. Our results suggest that the Yaa gene, unlike the lpr gene, exhibits selective autoimmune accelerating activity, but as a result of increased formation of certain nephritogenic autoantibodies such as anti-gp70 antibodies, the Yaa gene is able to accelerate the progression of lupus-like nephritis in lupus-prone mice. PMID- 2599004 TI - Different staphylococcal enterotoxins bind preferentially to distinct major histocompatibility complex class II isotypes. AB - The stimulation of T cells by staphylococcal enterotoxins (SE) is strictly dependent on major histocompatibility complex (MHC) class II-bearing cells. The interaction between SE and MHC class II molecules was studied on the human B cell lymphoma Raji and its MHC class II-negative variant RJ 2.2.5. Affinity purification with SEA and SEB matrix allowed the isolation of HLA-DR-like molecules from detergent lysates of 125I surface-labeled Raji cells, but not from RJ 2.2.5 cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis also revealed preferences in the binding of other SE such as SED, SEE and toxic shock syndrome toxin 1 to DR-like molecules, SEC2 to HLA-DQ-like molecules and SEC3 to DR- and DQ-like molecules. Preadsorption of the different MHC class II MHC isotypes confirmed the preferential binding of SEA to DR and of SEC2 to DQ. The implications of these findings for the understanding of SE-induced T cell activation and the potency of SE as a tool in the study of MHC class II antigens are discussed. PMID- 2599003 TI - Dynamics of early B lymphocyte precursor cells in mouse bone marrow: proliferation of cells containing terminal deoxynucleotidyl transferase. AB - Three populations of early B lymphocyte precursor cells lacking mu heavy chains have been defined in mouse bone marrow, based on immunofluorescence labeling for terminal deoxynucleotidyl transferase (TdT) and B220 glycoprotein, as detected by monoclonal antibody 14.8 (TdT+14.8- cells; TdT+14.8+ cells; TdT-14.8+ cells). We have now analyzed the frequency, size distribution, proliferation and production rates of TdT+ cells in mouse bone marrow. These formed well-defined populations of medium-sized cells, the TdT+14.8+ cells tending to be larger than TdT+14.8- cells (modal cell diameters in cytocentrifuge preparations; 10.0 microns and 9.0 microns, respectively). Some TdT+ cells (1%-2%) were normally in metaphase, the TdT being dispersed through the cytoplasm. After inducing mitotic arrest with vincristine, the incidence of TdT+ cells in metaphase increased linearly from 2 to 4 h, indicating a turnover of 5.1%/h for TdT+14.8- cells and 9.0%/h for TdT+14.8+ cells. Subtraction of turnover data for TdT+14.8+ cells from those previously obtained for 14.8+ mu- cells gave values for the population of TdT 14.8+ cells. The calculated daily turnover of cells in the three compartments increased progressively (TdT+14.8-, 2.5 x 10(6) cells; TdT+14.8+, 5.0 x 10(6) cells; TdT-14.8+, 36.0 x 10(6) cells), accompanied by a shortening of the average apparent cell cycle time (TdT+14.8-, 20 h; TdT+14.8+, 11 h; TdT-14.8+, 8 h). The results demonstrate a progressive expansion of cell production at three putatively successive stages of early B lymphocyte development before the expression of mu chains. The findings contribute to a kinetic model of primary B cell genesis in mouse bone marrow. PMID- 2599005 TI - Substitution of asparagine324 with aspartic acid in the Fc portion of mouse antibodies reduces their capacity for C1q binding. AB - The sequence of the heavy chain C region of mouse mutant IgG2a antibodies with reduced capacity for C1q binding but with retained ability for Fc receptor mediated functions was determined by cDNA cloning and by mRNA sequencing. The specific mutation was found to be the substitution of asparagine324 with aspartic acid. Asparagine324 represents a new residue relating to the C1q-binding sites previously described. PMID- 2599006 TI - Characterization, localization and pharmacological profile of a high-affinity [3H]lidocaine binding site. AB - Electrophysiological findings support the existence of voltage-dependent, sodium channel-associated receptors for class I antiarrhythmics. We have tried to identify such receptors with tritiated lidocaine. High-affinity binding sites were discovered in heart and brain membranes, but liver and kidney particulate fractions had the highest density of sites. The dissociation constants were 75 nM in bovine heart and 29 nM in guinea-pig liver membranes. Binding was reversible (t 1/2: 102 s at 2 degrees C), optimal at pH 9-10 and was only partly destroyed by heat treatment. Subcellular fractionation experiments excluded a plasmalemmal association of the lidocaine site in heart. The competition profile of 16 antiarrhythmics indicated chemical comparability of the sites in heart and liver. These data greatly challenge the applicability of labeled lidocaine as sodium channel probe. The pharmacological significance of the site described here remains to be clarified. PMID- 2599007 TI - Adrenergic and neuropeptide Y supersensitivity in denervated nasal mucosa vasculature of the pig. AB - The effects of sympathetic denervation for 2 weeks on vasoconstrictor reactivity to alpha-adrenoceptor agonists, neuropeptide Y (NPY) and alpha,beta-methylene adenosine triphosphate (mATP) were investigated in different vascular compartments of the nasal mucosa of pentobarbital-anesthetized pigs. Supersensitivity to the vasoconstrictor actions of noradrenaline (NA) was observed in the function of both resistance vessels (as revealed by a reduction in arterial blood flow) and capacitance vessels (reflected by a reduction in nasal mucosal volume). The NA supersensitivity was, to a large extent, of prejunctional type since inhibition of neuronal uptake by desipramine also markedly enhanced the NA response. Whereas the reduction in arterial blood flow and in mucosal volume induced by the alpha 1-agonist, phenylephrine, was not changed by denervation, the effects of the alpha 2-agonists UK 14.304 and oxymetazoline were enhanced and/or prolonged. Furthermore, the reduction in blood flow and volume induced by NPY was enhanced in both amplitude and duration. The effects of mATP on the amplitude of the volume response and the duration of the blood flow and volume changes were increased. The maximal reduction in superficial blood flow was larger, as revealed by the laser Doppler flowmetry signal, when NPY or adrenoceptor agonists were given to denervated animals. It is concluded that sympathetic denervation is associated with increased sensitivity and prolonged responses to a variety of vasoconstrictor agents in the pig nasal mucosa in vivo. However, alpha 2-adrenoceptor, NPY and mATP mechanisms seem to be influenced more by denervation than by alpha 1-adrenoceptor sensitivity. PMID- 2599008 TI - Triphasic inotropic response of guinea-pig papillary muscle to murrayaquinone-A isolated from Rutaceae. AB - Murrayaquinone-A, a carbazole alkaloid, was found to produce a triphasic inotropic response (first positive, second negative and third positive phases) of guinea-pig papillary muscle that normally paced at a slow rate of 0.2 Hz in Krebs Henseleit solution at 30 degrees C. Murrayaquinone-A produced a concentration dependent (10(-6) M-10(-4) M) positive inotropic effect (pD2 value 5.27 evaluated at the first phase). The triphasic pattern of inotropism of murrayaquinone-A was unaffected by reserpine, metoprolol or cimetidine treatment. Murrayaquinone-A increased the initial upstroke and the duration of the slow action potential in partially depolarized muscle (external K+ = 30 mEq). Murrayaquinone-A did not cause any positive inotropy under anoxic conditions and in the presence of 2,4 dinitrophenol and dicumarol. These results indicated that the triphasic inotropic effect of murrayaquinone-A is not mediated through a receptor mechanism but through a novel mechanism involving mitochondrial ATP production, thereby increasing the slow inward calcium current across the cardiac cell membrane via cyclic AMP converted from mitochondrial ATP. PMID- 2599009 TI - Opiate dependence alters central reward of nalbuphine or pentazocine plus tripelennamine. AB - The threshold lowering effects of the coadministration of tripelennamine plus nalbuphine or tripelennamine plus pentazocine on the threshold for rewarding electrical intracranial stimulation, a model of drug-induced euphoria, was determined in rats physically dependent to morphine. Although tripelennamine plus nalbuphine had threshold-lowering effects similar to tripelennamine plus pentazocine in non-opiate-dependent subjects, tripelennamine plus nalbuphine failed to lower the threshold for rewarding stimulation in morphine-dependent animals. To the extent that these data may be applied to human addicts, it suggests that opiate-dependent addicts are unlikely to use the combination of tripelennamine plus nalbuphine but are likely to use tripelennamine plus pentazocine. PMID- 2599010 TI - Potentiation of stretch-induced myogenic tone of dog cerebral artery by hemolysate and the inhibitory action of calcium antagonists. AB - Quick stretching of a helical strip of dog basilar artery at a rate of 10 cm/s to 140% of the slack length of the muscle evoked a delayed contraction. A small amount of hemolysate (0.01-0.2 mg/ml as hemoglobin), which increased the basal tone by 10-15% of the maximum contracture produced by 80 mM K+, potentiated the stretch-induced contraction 2- to 3-fold over the control. The enhanced response to stretch was attenuated by removal of the endothelium and was readily suppressed by Ca2+ antagonists such as nisoldipine and other dihydropyridine drugs as well as diltiazem. The hemolysate had no apparent effect on the contraction due to a quick stretch in Ca2+-free medium or on the contractile response of a chemically skinned arterial strip in the relaxing solution. The results suggest that the hemolysate potentiates the contractile response to stretch by promoting the transmembrane supply of Ca2+. The presence of endothelium seems to amplify the vasoconstrictor action of the hemolysate. PMID- 2599011 TI - Diazepam-insensitive [3H]Ro 15-4513 binding in intact cultured cerebellar granule cells. AB - [3H]Ro 15-4513, a partial inverse agonist at the benzodiazepine receptor, binds to two sites in the rat cerebellum, only one of which is sensitive to diazepam. The diazepam-insensitive component, whose identity is unknown, is unique to this brain area. We studied the binding of [3H]Ro 15-4513 in cultured cerebellar granule cells to characterize its binding sites in a specified neuronal cell population and to determine the effects of ethanol on the binding. We also compared the properties of [3H]Ro 15-4513 binding in washed membranes of cultured cells and 14-day-old rat cerebella. [3H]Ro 15-4513 had two binding components in intact granule cells, one sensitive to diazepam, that probably represents binding to the benzodiazepine agonist site, the other sensitive to an antagonist (Ro 15 1788) and two inverse agonists (ethyl-beta-carboline-3-carboxylate, beta CCE and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate, DMCM) of the benzodiazepine receptor (diazepam-insensitive binding). This diazepam-insensitive binding was stimulated by GABA; the maximal increase in binding was about 60% with an EC50 of 0.3 microM. The effect of GABA (10 microM) on the diazepam insensitive binding was unaffected by 100 microM nipecotic acid but was partially inhibited by 100 microM bicuculline. The stimulation by GABA was also seen at 37 degrees C with washed membranes of 14-day-old rat whole cerebella in the presence of micromolar diazepam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2599012 TI - Sexually dimorphic level of CCK-8-like immunoreactive neuronal somata within several basal forebrain nuclei of the rat. AB - Using indirect immunocytochemical technique CCK-8-like immunoreactive somata could be demonstrated in different basal forebrain nuclei of adult rat (olfactory tubercle, nucleus accumbens septi, nucleus tractus diagonalis BROCA, nucleus septi medialis et lateralis, caudate-putamen-complex). The comparison of these findings with those of rapid Golgi technique and AChE histochemistry suggested that all CCK-8 immunostaining nerve cells should be aspiny neurons and, partly at least, a coexistence of CCK-8 and acetylcholine is assumed. In the number of neuronal somata with CCK-8-like immunoreactivity in all nuclei, especially in the caudate-putamen-complex, a distinct difference between male and female rats exist. PMID- 2599013 TI - Activation of the sympathoadrenal system in rats during hypokinesia. AB - The levels of plasma epinephrine (E) and norepinephrine (NE) were examined in rats exposed to hypokinesia in special adjustable cages for 1, 7 and 75 days. One day before the collection of blood an arterial catheter was inserted into the tail artery and blood samples were collected from undisturbed animals on next day at 8 a.m. and after 1, 6, 12 and 24 hours later. The control groups of animals were kept single in standard animals cages. The content of E, NE and corticosterone was determined in plasma. In rats exposed to hypokinesia for the first time a marked increase of plasma E and NE levels were observed at 1 hour in forced restriction and both E and NE remained elevated after 6, 12 and 24 hours of hypokinesia. A permanent increase of NE and E content in plasma was found in rats exposed to hypokinesia for 7 and 75 days. However, the plasma corticosterone levels were increased only during the first day of hypokinesia, at 7 and 75 days no significant changes in plasma corticosterone were noted. These results showed that there is an important increase of plasma catecholamine levels immediately after the beginning of hypokinesia and the activation of sympathoadrenal system is maintained during the whole period of hypokinesia. No significant changes in adrenocortical system activity were noted during the long-term hypokinesia. PMID- 2599014 TI - Autoradiographic demonstration of glucocorticoid receptors in the intermediate lobe of the rat pituitary transplanted to the anterior eye chamber. AB - It is a general belief that the intermediate lobe of the pituitary, in contrast to the anterior pituitary, is devoid of glucocorticoid receptors. However, Antakly et al. (1985) using immunocytochemistry, demonstrated the presence of this receptor in intermediate lobe cells deprived of the hypothalamic innervation. It was the aim of the present study to confirm this finding by auto radiography, i.e., using an independent method. The neurointermediate lobe of adult male Wistar rats was syngeneic transplanted to the anterior eye chamber. The recipient rats were adrenalectomized 19 days after grafting and injected with [3H]corticosterone 5 days later. After a survival time of 60 min, autoradiograms were prepared by thaw-mount technique and quantitatively evaluated by silver grain counting. Beside the classical targets, anterior pituitary and hippocampal stratum pyramidale, the intraocular transplants showed a nuclear accumulation of radioactivity. This was abolished in rats treated for competition with an excess of unlabelled corticosterone prior to tracer application. No such receptor binding was found in the normotopic intermediate lobe and in the diaphragm studied as a non-target reference. Thus, this study confirmed that the glucocorticoid receptor gene is expressed if the tissue is grafted into an ectopic site. PMID- 2599015 TI - Arginine-vasopressin binding to isolated hippocampal microvessels of rats with different endogenous concentrations of the neuropeptide. AB - The binding of [125I]arginine-8-vasopressin (AVP) to hippocampal microvessels isolated from brains of normal Wistar rats, animals after water deprivation and heterozygous as well as homozygous diabetes-insipidus rats (Brattleboro strain) were measured. Data from binding experiments from the microvessels of the different groups of animals in each case revealed a single class of high affinity binding sites. However, the binding parameters between the different groups of rats were different. The affinity constants differs by a factor of 5.1, ranging from KD = 1.18 nmol X L-1 (animals after water deprivation) to KD = 6.05 nmol X L 1 (homozygous Brattleboro rats). The binding capacity, differing by a factor of 3.5, ranged from Bmax = 245 fmol X mg-1 to Bmax = 865 fmol X mg-1. PMID- 2599016 TI - Clinical aspects of surgery in primary hyperparathyroidism. AB - 60 patients suffering from primary hyperparathyroidism were operated during the period from 1980 till september 1988. The operation was successful in 55 cases. Most patients had single adenomas of the parathyroid glands. There was only one case with a four-gland-hyperplasia and one case with a parathyroid carcinoma. Rare observations were: one woman with a truly recurrent primary hyperparathyroidism, two patients with a papillary carcinoma of the thyroid gland in addition to the hyperparathyroidism and one patient with a large cystic parathyroid adenoma. Most of the patients had severe clinical symptoms of the primary hyperparathyroidism, mainly renal stones, in some cases bone changes. Only three patients were asymptomatic. PMID- 2599017 TI - Pathogenetic role of adipose tissue lipase deficit for development of hypertriglyceridaemia. AB - In 87 patients (74 males, 13 females; age 43 +/- 9.2 years) covering a wide range of triglyceride (TG) concentrations (8.8 to 80.7 mmol/l) the turnover of total serum TG has been measured using the technique of labelling endogenously synthesized TG with 3H-glycerol. In parallel, lipoprotein lipase activity in adipose tissue and the adipose-tissue lipase activity in post-heparin plasma have been assessed following an oral 50 g glucose load. Despite the well-recognized function of this enzyme for intravascular lipolysis no direct relationship between lipase activities and fractional catabolic rates (FCR), reflecting TG removal processes, was found. On the other hand, relative enzyme activities (per TG moles) are positively correlated with the FCR. However, a detailed analysis of this relationship revealed that only in HTG patients whose FCR are below 0.210 h 1 a rate-limiting influence of a relative lipase deficit can be shown. In these patients, a statistically significant elevation of concentrations of free fatty acids is supposed to contribute to the impairment of the TG removal. PMID- 2599018 TI - Pharmacokinetics of the progestin dienogest (STS 557) in rabbits. AB - Disposition and excretion of the progestin Dienogest (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9-dien-3-one, STS 557) were investigated in female rabbits. Following single and repeated administration of the tritium-labelled compound the plasma concentration courses of total radioactivity (Dienogest + metabolites) and of the parent drug alone were estimated and also the urinary and fecal excretion of total radioactivity. From these data basic pharmacokinetic parameters were calculated. Additionally, the enterohepatic recirculation of biliary excreted metabolites was studied using bile of donors for oral administration to recipients. Following oral administration the high bioavailability of Dienogest which was already found in other animal species and in man could also be confirmed with rabbits. The parameters of Dienogest disposition do not differ significantly from those of the progestin levonorgestrel. Thus, the different effects of the both progestins in the McPhail-Clauberg assay in the rabbit cannot be attributed to differences in pharmacokinetics. PMID- 2599019 TI - Studies on the biotransformation of the progestagen dienogest in the rabbit. AB - Following administration of 14 alpha, 15 alpha-3H-Dienogest (STS 557, 17 alpha cyanomethyl-17 beta-hydroxy-4, 9-estradien-3-one) to female rabbits, extracts from urine, bile and plasma were separated by means of HPLC. Urinary and biliary metabolites are characterized by patterns of high complexity. From the mass spectra and UV absorption data of the urinary Dienogest metabolites a variety of biotransformation reactions has been derived like: hydroxylation in different positions of the Dienogest molecule, among these the 11-position; reduction of the 3-oxo group to 3-hydroxy; introduction of 2 and 4 hydrogen atoms; aromatization of ring A; transformation of 17 alpha-CH2CN to CH2OH, and formation of compounds with a 5(10), 9(11)-diene structure. Some of these reactions occur simultaneously resulting in a very complicated metabolite spectrum. Possibly the multiple effects of Dienogest established in animals are partially caused by metabolites. PMID- 2599020 TI - Influence of a dopamine agonist (lisuride) on sex-specific behavioural patterns in rats. I. Short term effects. AB - Lisuride induces in juvenile male and especially in female rats a significant increase of the initiating activity in tests on social play-fighting behaviour. In neonatally castrated as well as in prenatally stress exposed males, castrated in adulthood, which exhibit under androgen alone bisexual or even predominantly heterotypical sexual behaviour, additional treatment with lisuride resulted in a temporary normalization of sexual orientation in the homotypical male direction. In castrated androgen treated females, lisuride induces a partial conversion of sexual orientation to heterotypical male direction. PMID- 2599021 TI - Influence of a dopamine agonist (lisuride) on sex-specific behavioural patterns in rats. II. Long-term effects. AB - Intact female and neonatally castrated male rats were treated with the dopamine agonist/serotonin antagonist lisuride during the early postnatal differentiation period of the brain (Day 2-12) or during the peripuberal maturation period (Day 26-40). It was found that early postnatal as well as peripuberal activation of the dopaminergic system in females resulted in masculinized social play-fighting behaviour, and lisuride application as late as peripuberally resulted in permanent masculinization of sexual behaviour. Comparable trends were found after peripuberal androgen administration. On the other hand, the demasculinized social play fighting as well as the sexual behaviour of neonatally castrated males, which is usually bisexual or even predominantly heterotypical, could be normalized--at least in part-by early postnatal or peripuberal lisuride administration. These findings confirm once more our previous reports that neurotransmitters can act directly as organizers of the brain. This holds true not only for the differentiation period but also for the maturation period. PMID- 2599022 TI - Oestrogen priming for the positive oestrogen feedback: site of action. AB - The significance of oestrogen priming for efficacy of the positive, ovulation inducing oestrogen feedback has been known for more than 15 years, but the site and mechanism of oestrogen action in the priming effect have not yet been elucidated. Long-term ovariectomized adult female rats were injected once or twice with 20 micrograms oestradiol benzoate (OB), and the serum LH concentration was estimated. Whereas a single injection of OB induced significant inhibition of LH secretion, high circulating LH levels were recorded in rats injected twice with the hormone at an interval of 48 h. This increase was prevented in ovariectomized females fitted with guide cannulae, if the antioestrogen clomiphene citrate was implanted into the medial preoptic area (MPOA) before the first injection of oestrogen and removed prior to the second. On the other hand, replacement of the first oestrogen administration by the implantation of a very low dose of OB into the MPOA resulted in stimulation of LH secretion. OB implants placed into the hypothalamic ventromedial-arcuate region were ineffective in this regard. Taken together, the findings suggest that the priming effect of oestrogen is mediated in rats, at least in part, by the MPOA. PMID- 2599023 TI - Postnatal treatment of rats with beta-adrenergic agonists or antagonists influences differentiation of sexual brain functions. AB - Sexual differentiation of the brain seems to be influenced by postnatal interaction of gonadal steroids with neurotransmitter systems, in particular the adrenergic system. Stimulation or inhibition of alpha-adrenergic receptors during early postnatal development had previously been shown to influence steroid induced sexual differentiation of brain functions. In the present study newborn male and female rats were treated either with salbutamol, a selective beta 2 adrenergic receptor agonist, isoprenaline, a general beta-adrenergic receptor agonist, or with alprenolol, a general beta-adrenergic receptor antagonist. In adulthood the female animals were ovariectomized and were tested for the capacity to show an LH-surge response and female sexual behaviour after priming with estradiol benzoate (EB) and progesterone (P). Male animals were tested for expression of male sexual behavior and, after gonadectomy and priming with EB + P, for the capacity to show female lordosis behavior. In summary, our results suggest that activation or inhibition of beta-adrenergic receptors during postnatal development permanently impairs the responsiveness of the center for cyclic gonadotropin release to gonadal steroids in female rats and impairs the expression of ejaculatory behavior in male rats. A slight stimulatory effect on the expression of female lordosis behavior was observed in male and female rats after postnatal activation of beta-adrenergic receptors. PMID- 2599024 TI - Thyroid hormone metabolism under extreme body exercises. AB - In two runs over a distance of 75 km and 45 km as well as in a marathon (42.2 km), the thyroid hormones (T4, T3 and TSH in all runs and rT3 in two of them) were determined before and after the runs. The performance of the runners was analyzed, with their age considered in the analysis. We found that the changes of thyroid hormones are characterized by individual differences. Younger runners and those with better performances had significantly higher T4 serum concentrations and unaltered T3 and TSH concentrations, whereas older sportsmen and those with worse performances reacted to the stressful stimulus with a significant decrease of T4, T3 and TSH. This response was interpreted as an exhaustion reaction, i.e. reduced adaptation responses of thyroid hormone metabolism. Therefore, these investigations provide an assessment of the state of fitness, the optimization of training and the avoidance of damage caused by overly stressful physical exercise PMID- 2599025 TI - Effect of endurance exercise on somatomedin-C/insulin-like growth factor I concentration in male and female runners. AB - By means of 3 endurance exercises, the effect of a several-hour intensive somatic stress on the changes of the Sm-C/IGF-I concentration was tested during, immediately after and on the day following the exercise. Exp. 1: Marathon with 17 male sportsmen in 2 groups with different glucose supply. Exp. 2: 45-km crosscountry run with 41 males. Exp. 3: Three 20-km runs with 8 young females at intervals of 3 months. In the marathon, no significant changes of the Sm-C/IGF-I concentration were found between the start, half distance and final values. The exogenous glucose supply (continuous or discontinuous) had also no effect. The tendency of a slight decrease of the Sm-C/IGF-I concentration by 0.14 U/ml (p greater than 0.05) was observed between start and finish in the 45 km crosscountry run lasting one hour longer. In the three 20-km runs, reproducible, slightly increased levels were measured at the end, whereas a decrease to the initial value or even below was detected on the following day (p greater than 0.05). The insignificant alterations of the Sm-C/IGF-I concentration measured in the 3 variants of races show that neither the hormonal changes stimulating the Sm C/IGF-I synthesis (e.g. increase of GH and prolactin) nor inhibiting factors (energy deficiency) clearly dominate during strenuous exercises. The binding of carrier protein prevents great variations of the Sm-C/IGF-I level even under the condition of 3- to 4-hour extreme endurance exercises. PMID- 2599026 TI - A digital image processing system for quantitating dynamic morphology in cultured mammalian cells. AB - An automated, video-driven system has been developed which can quantitate dynamic cell morphology in cultured mammalian cells. This system is based upon the Personal Image Analysis System and is assisted by a video-enhanced contrast microscopy with a computer-aided digital image processing unit and a time-lapse video technique. Various parameters for cell motility including locomotion (vectorial translation) and accompanying shape changes can be simultaneously analyzed. Here, we describe this system and demonstrate its application in Balb/c 3T3 cell culture. This system represents a new tool for exploring subtleties of mammalian cell behavior. PMID- 2599027 TI - Thrombin mitogenic responses and protein phosphorylation are different in cultured human endothelial cells derived from large and microvessels. AB - It is well established that thrombin induces various biological responses in endothelial cells derived from large vessels. However, little is known about the effects of thrombin on the microvasculature. Protein phosphorylation may be one of the mechanisms by which an extracellular stimulus initiates cellular events like proliferation. Therefore, we have compared the effects of either human alpha thrombin or phorbol esters (TPA) on the proliferation or protein phosphorylation in endothelial cells derived from large vessels (umbilical vein, HUVEC) or microvessels (omental tissue, HOMEC). In HOMEC, thrombin did not stimulate cell proliferation and protein phosphorylation while TPA slightly reduced the cell proliferation and induced the phosphorylation of a 27-kDa protein. In contrast, in HUVEC, thrombin or TPA markedly enhanced the cell proliferation and stimulated the phosphorylation of a 59-kDa protein. These data indicate that (i) endothelial cells from large and small vessels respond differently to thrombin and (ii) there is a complex and as yet unclear relationship between the proliferation and the protein phosphorylation induced by thrombin. PMID- 2599028 TI - Interferon beta increases expression of vimentin at the messenger RNA and protein levels in differentiated embryonal carcinoma (PSMB) cells. AB - Murine interferon beta increases expression of the 58-kDa intermediate filament protein vimentin by differentiated PSMB cells. Enhanced amounts of vimentin mRNA and protein have been detected using Northern hybridization and Western blotting techniques. Immunocytochemical analysis demonstrates the increased assembly of the protein into the intermediate filament network and its relocalization around the cell nucleus. Induction follows a defined time course, with peak protein levels 16 h post interferon addition, followed by a gradual decline over the next 36 h. PMID- 2599029 TI - Evidence that plasminogen activator is not involved in basement membrane penetration at avian gastrulation. AB - We have used the method of radial caseinolysis in agarose to assay for the presence of plasminogen activator in the primitive streak cells of the early chick embryo. These cells are undergoing an epithelial-mesenchymal transformation in the process of the differentiation of mesoderm cells from the ectoderm. In the primitive streak, the epithelial cells, after penetrating the basement membrane, ingress and invade the underlying tissue space as fibroblast-like mesenchyme cells. In contrast to some other early embryonic invasionary and migratory events, we find no evidence for the participation of plasminogen activator in this process. PMID- 2599031 TI - Insoluble disulfide cross-linked polypeptides accumulate in the functionally compromised lysosomes of fibroblasts treated with the cysteine protease inhibitor E-64. AB - Mouse fibroblasts (3T3-L1 cells) accumulate pulse-labeled long-lived polypeptides in detergent- and salt-insoluble aggregates when chased in the presence of inhibitors of lysosomal cysteine cathepsins, including E-64. Proteins found in the detergent- and salt-insoluble fraction include polypeptides which are disulfide cross-linked. E-64-induced polypeptide aggregates cofractionate with lysosomal enzyme markers on density gradients and are found in multivesicular dense bodies which by electron microscopy appear to be engaged in microautophagy. The results are discussed in relation to the possible role of polypeptide aggregation in the sequestration or trapping of cytoplasmic proteins by the lysosomal system. PMID- 2599032 TI - Effects of in vivo heat treatment on lampbrush chromosome structure in amphibian oocytes. AB - When Pleurodeles (Amphibian, Urodele) females were subjected to high temperatures (32-35 degrees C) for varying periods of time (45 min to 7 days), lampbrush chromosome structure underwent striking modifications. These changes included a numerical reduction in normal loops and progressive disorganization of RNP matrices of various loops. The degree of such disorganization was a function of the intensity and duration of the stress. These modifications were completely reversible when females or oocytes were returned to a normal breeding temperature (20 degrees C). Results are discussed in comparison with previous studies on morphological changes induced by heat shock in lampbrush chromosomes carried out in vitro. PMID- 2599030 TI - An increase in the intracellular pH of fertilized eggs of Xenopus laevis is associated with inhibition of protein and DNA syntheses and followed by an arrest of embryonic development. AB - In many systems, events participating in cell division are controlled by intracellular pH (pHi). In Xenopus eggs, fertilization is accompanied by an increase in pHi which occurs concomitantly with an increase in protein synthesis and a reinitiation of DNA synthesis, leading the embryo to cell division. In this paper, we have shown that increasing pHi of fertilized eggs from 7.8 to 8.2 by using weak bases produced an arrest in embryonic development. Such a change in pHi was accompanied by a severe inhibition of both protein and DNA syntheses. In order to discriminate between a direct effect of pHi and a pH-independent effect of weak bases on these biosyntheses, the situation was studied in vitro. For this purpose, cytoplasmic extracts were used in which weak base addition did not produce any change in pH. Under these conditions, protein synthesis was not inhibited, suggesting that pH is probably one of the events implicated in the regulation of protein synthesis. On the other hand, DNA synthesis was inhibited by weak bases in vitro, without any change in pH intervening. PMID- 2599033 TI - Whole-cell currents in olfactory receptor cells of Xenopus laevis. AB - Olfactory mucosae of Xenopus laevis were dissociated without enzymatic treatment and the isolated olfactory neurones were studied with the tight-seal whole-cell recording configuration of the patch clamp technique. In the voltage clamp, five current components could be distinguished: a fast, TTX-sensitive Na+-current, a small and slow inward current carried by Ca2+ ions, a Ca2+-dependent K+-current, a K+-current which activates rapidly at voltages more positive than -20 mV and quickly inactivates, and a slowly activating and very slowly inactivating K+ current. Some of the characteristics of the whole-cell currents herein reported contradict previous findings while others verify them, thereby allowing a tentative interpretation of their physiological role in the transduction process. PMID- 2599034 TI - Slow synaptic inhibition in relation to frequency habituation in dentate granule cells of rat hippocampal slices. AB - In paired pulse stimulation experiments the mechanism underlying frequency habituation of postsynaptic potentials in dentate granule cells of rat hippocampal slices was studied by measuring extra- and intracellular potentials as well as changes in extracellular calcium [( ([Ca2+]0) and potassium concentrations ([K+]0). Orthodromic stimulation of the perforant path induced in most granule cells a late, slow hyperpolarization (SH), lasting for up to 1.2 s. During the SH the membrane conductance was increased by up to 40%. The reversal potential of the SH was around -90 mV and varied with the [K+]0. Frequency habituation was seen in all cells with the SH, whereas cells which display frequency potentiation had no SH. Lowering of [Ca2+]0 reversed paired pulse induced frequency habituation into frequency potentiation at [Ca2+]0 levels where the SH disappeared. Phaclofen blocked the SH and reversed frequency habituation into frequency potentiation. Elevating [Mg2+]0 also reversed frequency habituation into frequency potentiation and reduced the SH. We conclude that the SH represents a late, slow IPSP which is responsible for frequency habituation in dentate granule cells. We noted that during repetitive stimulation the SH soon started to fade. This effect can in part be attributed to extracellular K+ accumulation as suggested by the K+-dependence of the slow IPSP and the observations of changes in [K+]0 during repetitive stimulation. This could explain why frequency habituation reverses into frequency potentiation during repetitive stimulation. PMID- 2599035 TI - Differential effects of retinal target displacement, changing size and changing disparity in the control of anterior/posterior and lateral body sway. AB - When visual information is provided in addition to input from other sensory systems, normal body sway can be attenuated by about 50%. The essential visual cue is retinal target displacement, which increases as eye-target distance is reduced. As a result, both lateral and anterior/posterior (A-P) sway decrease as eye/target distance decreases. We have investigated the geometrical basis of lateral and fore-aft sway detection by vision, the latter provided by detection of change in disparity of the visual axis of both eyes and change in target size. Using known movement detection thresholds the largest possible distance for visual stabilization of posture can be calculated to be 34 m for lateral sway, and for fore-aft sway 1.50 m for change in disparity and 3.20 m for change in size. Visual stimuli were designed to selectively stabilize fore-aft sway either by change in size or by change in disparity. The experiments revealed that the theoretical prediction overestimates the efficacy of visual stabilization of lateral sway and underestimates the efficacy of fore-aft sway stabilization. It is proposed that microoscillations of the eye increase the threshold for detection of retinal target displacements, leading to less efficient lateral sway stabilization than expected, and that the threshold for detection of self motion in the A-P direction is lower than the threshold for object motion detection used in the calculations, leading to more efficient stabilization of A-P sway. PMID- 2599036 TI - Saccadic reaction times, eye-arm coordination and spontaneous eye movements in normal and MPTP-treated monkeys. AB - The oculomotor performance of monkeys was investigated before and after destruction of nigrostriatal dopamine neurons by MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine). Stimulus-triggered saccades and their relationships to arm movements were measured in a reaction time task. Spontaneous eye movements were recorded while monkeys sat in a primate chair and looked around the laboratory without performing any task. In the reaction time task, saccades and arm movements were commonly triggered by the rapid, visible and audible opening of a small food-containing box which was located at a constant position in front of the animal at eye level. Median saccadic latencies ranged from 68 to 118 ms in intact animals. Saccades were followed by onset of electromyographic (EMG) activity in the extensor digitorum communis and the biceps brachii, the prime mover muscles for the following arm reaching movement. Latencies of stimulus triggered saccades showed an absence of linear relationship to EMG or arm movement reaction time in intact animals (correlation coefficients of 0.15-0.56). This suggests that eye and arm movements were initiated independently from each other in this experimental situation. Treatment with MPTP resulted in 98-99.5% loss of striatal dopamine in both monkeys. This induced a 29-93% increase in saccadic latency in the reaction time task. The sequential occurrence of saccade, EMG activity and arm movement in each trial was preserved, although intervals between onset of saccades and onsets of EMGs and arm movements were prolonged by 53-173% and 33-679% respectively. Onsets of individual saccades remained uncorrelated with onsets of EMG activity or arm movement. Spontaneous eye movements were strongly reduced in frequency and amplitude after MPTP. Administration of the dopamine precursor L-Dopa increased spontaneous eye movements for less than two hours. The severe deficits in stimulus-triggered and spontaneous saccadic eye movements are oculomotor components of hypokinesia arising after MPTP-induced lesions of the nigrostriatal dopamine system in primates. The data are further evidence for a role of midbrain dopamine neurons in behavioral responsiveness and spontaneous activity. PMID- 2599037 TI - Ischemia-induced changes in the electrical activity of the hippocampus. AB - Consequences of transient (15-20 min) ischemia on the neuronal activity of the dentate gyrus and hippocampal CA 1 region were investigated in chronically implanted Sprague-Dawley rats. Forebrain ischemia was produced by occlusion of the carotids for 15 or 20 min, following cauterization of the vertebral arteries. Following the release of the carotids, both spontaneous and evoked activity showed a steady but partial recovery, reaching a maximum 12 to 24 h after the ischemic insult. From this plateau, both the power of rhythmic slow activity recorded during walking and the power of slow delta activity obtained during alert immobility decreased monotonically, with large changes occurring between postischemic days 2 and 4. The changes in spontaneous activity were accompanied by a decrease and eventual disappearance of the Schaffer collateral evoked responses in CA 1. Perforant path volleys were less efficient in activating the granule cells following ischemia compared to baseline levels. This decreased responsiveness was paralleled by a relative impairment of paired pulse depression. Neurophysiological signs of spontaneous or evoked neuronal hyperexcitability were not observed at any time point during the 8 postischemic days. Neuronal damage in the CA 1 region varied from moderate to complete loss of pyramidal cells. In addition, degenerating neurons were also observed in the hilus of the dentate gyrus. These findings do not support the "overwork" version of the excitoxic hypothesis of delayed neuronal damage and indicate that the cause of ischemic cell death should be sought in factors other than neuronal hyperactivity. PMID- 2599039 TI - Migration of immature neurons along tangentially oriented fibers in the subpial part of the fetal mouse medulla oblongata. AB - Migration of neuronal cells in the subpial part of the medulla oblongata was examined in the fetal mouse by light and electron microscopy. Cells were observed forming a migratory stream in the period between the thirteenth and sixteenth days of gestation, and were associated with tangentially oriented fibers. Many of these tangential fibers were present prior to the onset of the migration, and the fibers were filled with longitudinally arrayed microtubules. The cell-bodies were elongated and arranged along, and often apposed to the fibers. Some relocating neurons extended fibers, i.e. leading processes, in the direction of the migration. Generally, these cells exhibited features of immature neurons; they displayed a high concentration of ribosomal rosettes and contained mitochondria, Golgi apparatus, a few rough endoplasmic reticula, and occasionally, centrioles. Junctional complexes, coated pits and coated vesicles were frequently observed in the region of the migratory stream, and these structures are considered to be related to cell locomotion. The present findings strongly suggest that such tangential fibers, including leading processes of moving neurons, serve as guidance substrates for the relocation of immature neurons in the mouse subpial medullary region. PMID- 2599038 TI - Morphometric analysis of prefrontal cortical development following neonatal lesioning of the dopaminergic mesocortical projection. AB - In this study the possibility that dopamine (DA) plays a trophic role in cortical development was studied by analysing cortical morphology and dendritic arborization of pyramidal cells after neonatal depletion of DA. The prefrontal cortex (PFC) was depleted of a DA innervation from postnatal day 1 onwards by thermal lesions of the DA cell group (A10) in the ventral tegmental area. Measurements of the cortical thickness and volume of the PFC subareas did not reveal any gross alterations. The DA-depleted animals, however, showed a 30% decrease in the total length of the basal dendrites of the pyramidal cells in layer V of the medial PFC. These cells constitute the primary target of the dopaminergic innervation in the prefrontal cortex. The decreased dendritic length was due mainly to a reduced branching frequency of the basal dendrites. The present results of the dendritic measurements support a trophic role for DA in neuronal differentiation. PMID- 2599040 TI - Human optokinetic nystagmus is linked to the stereoscopic system. AB - It was previously proposed that a linkage between the optokinetic system and the stereoscopic system in higher mammals serves to allow these animals to selectively stabilize those parts of the visual scene which lie in the plane of convergence as the animals move forward in a three-dimensional world (Howard and Ohmi, 1984). A new procedure is now described by which OKN gain can be measured as a function of the binocular disparity of the stimulus. With vergence locked on a vertical line, the gain of the slow phase of vertical optokinetic nystagmus (OKN) was recorded in four human subjects as the binocular disparity (stereo depth) of the moving display was changed from -3 degrees to +3 degrees. The gain of OKN was found to be inversely proportional to binocular disparity. Evidence for cells in the visual cortex, MT and MST that are sensitive both to visual motion and binocular disparity is reviewed. It is argued that the activity of cells responsive to direction of motion and zero disparity selectively augments OKN and that this enables humans to stabilize the images of parts of the scene in the plane of regard while ignoring competing motion signals arising from other distances. PMID- 2599041 TI - Identification of vestibular efferent neurons in the gerbil: histochemical and retrograde labelling. AB - The efferent neurons of the gerbil vestibular system were investigated by retrograde tracing techniques and cytochemical staining for acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and a number of peptides. The location, bilateral distribution, cell area and number of neurons in two identified groups of retrogradely labelled cells were described and quantified. The larger of the two groups was located dorsolateral to the facial nerve genu, ventral and medial to the vestibular nuclei. Unilateral tracer injection in the vestibular end organs labelled cells bilaterally in this and the smaller group, which was located immediately ventral to the genu. No cells were found that individually projected bilaterally to both labyrinths. After injections of horseradish peroxidase (HRP) in the utricle or saccule, significantly more cells were located on the contralateral side of the brainstem. The average (+/- SD) cross sectional area of labelled cell bodies associated with the otolith organs was 259.8 (+/- 75.2) microns 2. ChAT immunoreactive and AChE positive cells were found in an area coextensive with the location of the dorsal efferent group. In double labelling studies, cell bodies in the same group that had been retrogradely labelled with a utricular injection of HRP, were immunocytochemically stained for calcitonin gene-related peptide and met-enkephalin. In contrast, the ventral group of efferents did not have cells that were cytochemically stained for either of the acetylcholine-related enzymes or either peptide. The significance of the existence of peptidergic vestibular efferent neurons is discussed. PMID- 2599042 TI - Central distributions of the efferent and afferent components of the pharyngeal branches of the vagus and glossopharyngeal nerves: an HRP study in the cat. AB - The central distributions of efferent and afferent components of the pharyngeal branches of the vagus (PH-X) and glossopharyngeal (PH-IX) nerves in the cat were studied by soaking their central cut ends in a horseradish peroxidase (HRP) solution. HRP-labelled PH-X neurones were distributed ipsilaterally in the rostral part of the nucleus ambiguus (NA) and the retrofacial nucleus (RFN); HRP labelled PH-IX neurones were found in the ipsilateral RFN and the bulbopontine lateral reticular formation (RF). Vagal pharyngeal neurones constituted a large population of brainstem motoneurones. The population of HRP-labelled glossopharyngeal neurones was divided into two components. Indeed, on the basis of their location and somal morphology, the most ventral cells were identified as cranial motoneurones and those scattered in the lateral RF as parasympathetic preganglionic neurones. Application of HRP to the PH-IX nerve resulted also in the labelling of fibres and terminals in the alaminar spinal trigeminal nucleus and the nucleus of the solitary tract (NTS). The afferent fibres entered the lateral medulla with the glossopharyngeal roots, ran dorsomedially, then turned caudally toward the NTS and the caudal part of the alaminar spinal trigeminal motor (V) nucleus. In the NTS, labelled fibres ran mainly along the solitary tract, projecting to terminals in the dorsal and dorsolateral nuclei of the NTS. PMID- 2599043 TI - Pharyngeal motoneurones: respiratory-related activity and responses to laryngeal afferents in the decerebrate cat. AB - In decerebrate, paralyzed and artificially ventilated cats, we recorded the discharge of 64 motor axons supplying the pharyngeal muscles. Filaments containing motor axons, with discharges related to the respiratory cycle (phrenic nerve activity), were teased from the pharyngeal branches of the vagus and glossopharyngeal nerves. Most units (n = 41) fired only during expiration and exhibited a steady, a decreasing or a late augmenting discharge pattern. These units were found only in vagal filaments. Twenty three units discharged during inspiration and exhibited a steady, a late augmenting or a tonic discharge pattern. The inspiratory-related units were present in both the vagus (n = 13) and glossopharyngeal (n = 10) nerves. Nineteen of 20 pharyngeal inspiratory related units tested were activated at short latency (range 3.4 to 8.0 ms) by stimulation of afferents in the superior laryngeal nerve (SLN). In 13 of these, such stimulation also suppressed their spontaneous activity, SLN stimulation elicited in all 17 pharyngeal expiratory-related units tested a short latency (range 0 to 8 ms) reduction of activity, followed in 7 units by an increase in activity. SLN stimulation occasionally evoked single or rhythmic multifibre bursts in the vagal pharyngeal filaments. These bursts, involving expiratory related units, likely correspond to the buccopharyngeal stage of swallowing. PMID- 2599045 TI - Behavioural thermosensitivity after unilateral, partial lesions of the lateral funiculus in the cervical spinal cord of the cat. AB - Adult cats were tested for unilateral, behavioural thermosensitivity, before and after unilateral, surgical lesions involving part of the lateral funiculus of the cervical spinal cord. Contralateral thermosensory deficiencies were found after lesions, which involved the middle parts of the lateral funiculus. No such deficiencies were observed after lesions which were restricted to either the dorsal third, or the ventral half of the lateral funiculus. It was concluded that behaviourally important, thermosensory information is transmitted via an ascending pathway which is located ventrally in the dorsal half of the lateral funiculus. PMID- 2599044 TI - Neurotensin-induced excitation of neurons of the rat's frontal cortex studied intracellularly in vitro. AB - The actions of neurotensin (NT) on frontal pyramidal neurons were studied in vitro in slices of rat cerebral cortex using current clamp and single electrode voltage clamp (SEVC) techniques. Bath application of NT (0.1 microM-10 microM) induced a depolarization (2-13 mV) in 88% of the pyramidal cells, this effect was associated with a decrease in input conductance of 5-35% and its reversal potential was estimated at -88 +/ -9.7 mV. Typically, this depolarizing effect of NT was transient, since no cell responded to a second application of the peptide within 20 min after the first one. NT also induced an increase in the rate of firing of pyramidal cells evoked by direct stimulation, even when an hyperpolarizing current was applied to prevent the depolarization induced by NT. This effect could neither be explained by a decrease of the post-spike after hyperpolarization, nor by an increase of the persistent sodium current which sustains the spiking of pyramidal cells, since the former was not affected consistently by NT and the later was insensitive to the peptide. This excitation of pyramidal neurons by NT persisted after blockade of synaptic transmission. On the other hand, NT also enhanced the synaptic noise recorded in pyramidal cells in standard perfusing medium. Furthermore, dopaminergic antagonists and noradrenergic antagonists failed to block these effects of NT. Finally, the inactive fragment of the peptide, NT(1-8), did not affect membrane properties of pyramidal cells. All together, these results suggest that NT excites frontal cortical neurons through the activation of specific NT receptors. PMID- 2599046 TI - Behavioural thermosensitivity after bilateral lesions of the lateral funiculi in the cervical spinal cord of the cat. AB - The behavioural thermosensitivity of six cats was measured before and after single stage, symmetrical, bilateral, surgical lesions of the cervical spinal cord. The lesions were aimed at an area in the most ventral parts of the dorsal halves of the lateral funiculi. Unilateral lesions of that area have previously been found to cause reproducible, although subtotal, contralateral thermosensory defects, which were attributed to interruption of the thermosensory spinothalamic pathway. The lesions of three of the present cats were found to be incomplete, and those animals showed no postoperative thermosensory deficiency. Two of the cats with complete lesions showed marked post-operative defects, especially immediately after the operations, but the third cat with a complete lesion showed no postoperative thermosensory defect at all. The differences between the last three animals have been compared to the irregularity of previous reports about thermosensitivity after spinal cord lesions in man and animals, and may depend on the testing technique, rather than differences of thermosensitivity per se. PMID- 2599047 TI - Visual response properties of pretectal units in the nucleus of the optic tract of the opossum. AB - Single-units were recorded from the nucleus of the optic tract. Most of the units showed excitation in response to random check patterns presented on a tangent screen to the contralateral eye, moving in a temporal to nasal direction and/or inhibition in the opposite direction. The excitatory response to the temporal to nasal movement, observed in most units, was unchanged throughout the range of speeds tested, except for a decrease at the slowest (0.6 deg/s) and fastest (150 deg/s) speeds. On the other hand, the inhibitory responses evoked by a nasal to temporal movement, had a peak between 3 and 16 deg/s which decreased towards both extremes. An average of 45% of the units were influenced by the stimulation of the ipsilateral eye. In one third of them the response was very weak. In the remainder, the mean frequency of spikes in one direction of the horizontal movement was more than twice that in the opposite stimulus direction. In the great majority of these units, stimulation of each eye yielded the same overall pattern of directionality, that is, movement of the stimulus towards the recording side led to excitation and/or movement in the reverse direction led to inhibition. Inhibition was stronger than excitation in most ipsilaterally responding units. Excitatory responses elicited by the ipsilateral eye were always weaker than those by the contralateral but in a few cases the ipsilateral inhibitory component was more prominent than the contralateral one. PMID- 2599048 TI - Control of feeding movements in the pteropod mollusc, Clione limacina. AB - (1) The buccal apparatus of the pteropod marine mollusc Clione limacina, isolated together with buccal ganglia, could perform rhythmic feeding movements. Movements of the radula and the hooks (which the Clione inserts into the body of its prey) as well as the electroneurogram of the radular nerve were recorded. Usually one could observe rhythmic radula movements alone, while the hooks were motionless. But sometimes the hooks also performed rhythmic movements which were more or less synchronous with those of the radula. The radula movement cycle consisted of the protraction and the retraction phases, which were occasionally followed by a quiescent phase. Corresponding to each radula movement was a burst of activity in the radular nerve, consisting of the protractor and the retractor components. (2) Isolated buccal ganglia were capable of feeding rhythm generation. Most of the buccal neurons exhibited rhythmic activity correlating with the activity in the radular nerve. According to the phase of activity in the feeding cycle, rhythmic neurons were divided into two groups - the protractor and the retractor ones. The neurons within each of the groups were electrically coupled with each other. The protractor and retractor neurons inhibited each other. (3) Protractor and retractor neurons were extracted from buccal ganglia by means of a microelectrode. Many isolated cells generated slow oscillations of membrane potential and bursts of spikes, the pattern of this activity being similar to that before isolation. (4) A model of the feeding rhythm generator is discussed. It consists of two (protractor and retractor) groups of neurons with mutual inhibitory connections, neurons of each group being endogenous bursters. PMID- 2599049 TI - Control of locomotion in marine mollusc Clione limacina. VII Reexamination of type 12 interneurons. AB - In previous work carried out on the isolated pedal ganglia of the pteropod mollusc Clione limacina we described the activity of a neuronal element (type 12 neuron) and looked into its role in the locomotor rhythm generation (Arshavasky et al. 1985d). As we learned subsequently, the activity was recorded from the neuron axon passing in the pedal ganglia, while the neuron soma was located in the pleural ganglia and consequently was cut off in the course of pedal ganglia isolation. It thus became necessary to reinvestigate the properties of this neuron and its role in locomotory rhythm generation by using less reduced preparation of the central nervous system. The following results were obtained. (1) Each pleural ganglion contains only one neuron of this type, this cell is thus to be considered as the identified neuron. The neuron's axon reaches into the pedal ganglion via the pleuro-pedal connective. Then the axon divides into two branches terminating in the lateral regions of both pedal ganglia. The neurons 12 from the left and right pleural ganglia have no direct connections with one another; their synchronous operation in the locomotor cycle is determined by common inputs. (2) The electrical properties of an intact neuron 12 and one without a soma are about the same. In either case the neuron generates "plateau" potentials, i.e., it may persist for a long time in the depolarized state. Plateau potentials can be induced by a depolarizing current pulse or by an EPSP, and terminated by hyperpolarizing current or by an IPSP. The neuron input resistance drops about twofold during generation of the plateau potential.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2599050 TI - Sensory and affective aspects of pain perception: is medial thalamus restricted to emotional issues? AB - Lateral and medial thalamus are traditionally thought to have separate roles in pain processing, with lateral lemniscal regions transmitting discriminative information about location and intensity, while medial nonspecific regions are involved in emotional responses. Contrary to this view, the present study shows that some single neurons in medial thalamus of alert monkey discriminate changes in the intensity of noxious stimuli that are equal to or below the monkey's own discrimination threshold. Since these neurons are also modulated by anesthesia and attentional factors, we suggest that parts of medial thalamus may participate in both discriminative and affective dimensions of pain. PMID- 2599051 TI - Mechanical sensibility of the sole of the foot determined with vibratory stimuli of varying frequency. AB - The mechanoreceptive properties of the sole of the foot were determined by measuring the detection thresholds to vibratory stimuli of 20, 80, and 240 Hz frequency and 300 ms duration. The thresholds were measured at six different sites on the left sole and at toes 1 and 3 with probes of 2 and 8 mm diameter connected to the moving coil of an electromechanical vibrator. The subject sat in an armchair during the experiments, with the left leg supported horizontally by a vacuum cast positioned on a table. Six subjects participated in the experiments. A simple method of limits was used to make the measurements. Lower average thresholds were obtained with higher vibration frequencies, the average thresholds varying between 40-90 microns at 20 Hz and well below 10 microns at 240 Hz. The major decrease in thresholds occurred between 20 and 80 Hz. Interindividual variability in thresholds was large, but the threshold curves obtained from different subjects and from different stimulation points were of the same general shape. The highest thresholds were measured from the toes, but this regional differences in sensibility was obtained only at the higher vibration frequencies. Comparison of the threshold values at the sole with those found with similar stimuli at the thenar eminence and middle fingertip indicates that the mechanoreceptor mechanisms transmitting information about low-frequency vibration in the sole are similar to those in the palmar skin of the hand. PMID- 2599052 TI - A quantitative analysis of the synaptic development of the lobus parolfactorius of the chick (Gallus domesticus). AB - The lobus parolfactorius (LPO) of the chick has been shown to undergo an increase in the mean synaptic numerical density (Nvsyn) in response to one-trial passive avoidance learning (Stewart et al. 1987). The present study was undertaken in order to describe the pattern of normal development of synapses in the LPO, to further investigate the significance of this plastic response. The LPO's from each hemisphere of pre-hatch (16 days), and post-hatch (1 day, 9 day and 22 day old) chicks were processed for electron microscopy. Synapses were classified into asymmetric spine, asymmetric shaft, symmetric spine, and symmetric shaft synapses, on the basis of the density of the post-synaptic thickening and the nature of the post-synaptic target. A 3-dimensional stereological probe was used (the 'disector') to calculate Nvsyn, and mean projected height (Hsyn) of the post synaptic density (PSD). Mean values for each age and hemisphere were compared with a 2-way analysis of variance test using paired samples. A six-fold increase in Nvsyn was seen between 16 days in ovo, and 9 days post-hatch. There was a hemispheric asymmetry at 9 days post-hatch, with the left hemisphere LPO containing 1.6 times as many synapses per micron-3. There was a subsequent period of reduction in synaptic density in the left hemisphere LPO between 9 and 22 days post-hatch. The Nv of all classes of synapse increased with age, but the proportions of the symmetrical synapses with respect to the total number of synapses, decreased with age. This decrease was of a similar magnitude for each hemisphere. A hemispheric difference was seen in post-hatch asymmetric synapses, with a greater proportion of asymmetric spine synapses in the left hemisphere. The magnitude of the hemispheric asymmetry was constant throughout the 3 week period of post-hatch development, but was not present in pre-hatch chicks. The PSD increased in length in each hemisphere by approximately 40% between post hatch day 1 and post-hatch day 9. These data show that the LPO contains a synaptic population which undergoes substantial modification during the first week post-hatch. An asymmetry exists at post-hatch day 9 which is not present at the earlier ages investigated, nor indeed after 22 days post-hatch. This may have significance with regard to studies of passive avoidance learning in the one-day old chick, where an increase in both the size and number of synapses in the LPO has been demonstrated (Stewart et al. 1987).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2599054 TI - Solid state fermentation for cephalosporin production by Streptomyces clavuligerus and Cephalosporium acremonium. AB - Solid state fermentation systems were developed for the production of cephalosporins with Streptomyces clavuligerus and Cephalosporium acremonium. S. clavuligerus NRRL 3585 was grown on moistened barley under optimum solid state fermentation conditions for 7 days; approximately 300 micrograms cephalosporins per g substrate were extracted from the kernels. C. acremonium C-10 produced approximately 950 micrograms cephalosporin C per g substrate after 10 days of solid state fermentation. PMID- 2599053 TI - Relationship of afferent inputs to the lattice of high NADPH-diaphorase activity in the mouse superior colliculus. AB - In the intermediate gray layer of the superior colliculus there is a lattice of high NADPH-diaphorase activity which represents the terminal distribution of a number of extrinsic afferent systems. These include inputs from the dorsal cholinergic column and cells in the precommissural nucleus and dorsolateral wedge of the central gray substance. Other afferents that terminate in the intermediate gray layer, such as the input from the nucleus of the brachium of the inferior colliculus (BIN), are almost completely segregated from the above inputs and show very little overlap with the NADPH-diaphorase lattice. It is suggested that the input from the precommissural nucleus and central gray substance may have a role in nociception while the input from BIN may provide an important source of auditory information. PMID- 2599055 TI - Exogenous melatonin: morphology and kallikrein activity of male Syrian hamster submandibular gland. AB - Seven weeks of daily melatonin administration resulted in substantial reduction of convoluted duct cell granule population and kallikrein activity. Some reduction of intercalated duct cell granules was also observed. Testes weight and size was also dramatically reduced. All these changes were not observed after three weeks of melatonin injection. PMID- 2599056 TI - Determination of cerebrospinal fluid and serum lead levels in patients with amyotrophic lateral sclerosis and other neurological diseases. AB - In a total of 62 samples of cerebrospinal fluid (CSF) and an equal number of serum samples obtained from 16 patients suffering from amyotrophic lateral sclerosis, 22 patients suffering from miscellaneous neurological diseases, and 24 controls, lead was measured by atomic absorption spectrophotometry. No statistical difference in lead concentration was found between the above three groups. PMID- 2599057 TI - Comparative platelet anti-aggregant activity of D-cysteinolic acid analogues. AB - D-Cysteinolic acid (1) analogues with an S-C-C-N skeleton showed increased platelet anti-aggregant activity in the following order: 2-aminoethanesulfonic acids, thiazolidines, 2-aminoethanethiols and 2-aminoethyl disulfides. Methyl substitutions at the 2-position potentiated the activity. Of these analogues, bis [(R)-2-aminopropyl] disulfide was the most potent inhibitor of platelet aggregation, with about 600-fold the activity of (1). PMID- 2599058 TI - Number of glucocorticoid receptors in lymphocytes and their sensitivity to hormone action. AB - The study demonstrated a decreased level of glucocorticoid receptors (GR) in peripheral blood lymphocytes from hypercholesterolemic subjects, and an elevated level in patients with acute myocardial infarction. In the lymphocytes with a high GR number, dexamethasone inhibited [3H]-thymidine and [3H]-acetate incorporation into DNA and cholesterol, respectively, in the same manner as in the control cells. On the other hand, a decreased GR number resulted in a less efficient dexamethasone inhibition of the incorporation of labeled compounds. These data showed that the sensitivity of lymphocytes to glucocorticoids changed only with a decrease of GR level. PMID- 2599059 TI - Effects of estradiol on parathyroid cell activity. AB - Beta-estradiol-3-benzoate provoked an initial centrifugal membrane shift in rat parathyroid cells and, later, enlargement of the compartments concerned with parathyroid hormone secretion, which suggests that estradiol modulates not only transport and release of parathyroid hormone but also the capacity for its synthesis, packaging and storage. PMID- 2599060 TI - Suppression of mitogen- and antigen-induced lymphocyte proliferation by lanthanides. AB - Lanthanide ions (Ln3+) inhibited the proliferative response of human lymphocytes to various polyclonal mitogens and the 'purified protein derivative' (PPD) of the tuberculin antigen. Of the four Ln3+ ions tested lanthanum (La3+) was the strongest inhibitor; erbium (Er3+) and lutetium (Lu3+) were only weakly active, while samarium (Sm3+) had intermediate potency. At a concentration of 1 mM, La3+ almost completely inhibited the uptake of [3H]-thymidine by lymphocytes exposed to mitogenic agents. Trypan blue exclusion tests confirmed that the La3+ ions were not toxic. These findings may bear upon the reported anti-inflammatory properties of the lanthanides. PMID- 2599061 TI - Proliferation of primordial germ cells of frogs stimulated by a fraction of granules derived from Rana nigromaculata embryos at the tail-bud stage. AB - A fraction of heavy granules, obtained from embryos of the frog (Rana nigromaculata) at the tail-bud stage by centrifugation at 1700 x g, were shown to stimulate the formation of proliferation of the primordial germ cells not only of the same species but also of a closely related species. PMID- 2599062 TI - Stimulated intraphagosomal release of eosinophil peroxidase and acid phosphatase in the rats spontaneously infected with Mycoplasma pulmonis: a cytochemical study. AB - In this study we performed a cytochemical comparison of peroxidase and acid phosphatase activities in peritoneal eosinophils from specific pathogen-free (SPF) and Mycoplasma pulmonis-infected rats. When eosinophils ingested polystyrene particles for 120 min, peroxidase- and acid phosphatase-positive specific granules, as well as small granules, fused to phagosomes. Unusual peroxidase activity was detected in some particle-containing phagosomes in 6.8% of eosinophils from control SPF rats and 31% of those from infected rats. Intense acid phosphatase activity was also demonstrated in some phagosomes in 4 and 20% of eosinophils from control and infected rats, respectively. The rate of peroxidase-positive and acid phosphatase-positive phagosomes to all ingested phagosomes was 8.1 and 7.3% in control rats and rose to 41.3 and 31.1% in those infected, respectively. The population of eosinophils (18%) in the control peritoneal cells did not change after infection (16.6%). These results suggest that the intraphagosomal release of lysosomal enzymes was significantly stimulated in peritoneal eosinophils of the rats spontaneously infected with M. pulmonis. PMID- 2599063 TI - Relationship between sarcolemmal damage and appearance of amorphous matrix densities in mitochondria following occlusion of coronary artery in rats. AB - The relationship between the progression of sarcolemmal damage and the appearance of amorphous matrix densities (AMDs) within myocardial mitochondria in the early phase of ischemia was studied in coronary-ligated rats by means of electron microscopy. The animals were divided into six groups according to the duration of ischemia (from 10 to 120 min). The severity of sarcolemmal damage was graded into four classes according to the ultrastructural ischemic changes, as follows: grade 0, normal cells; grade 1, slight ischemic changes in cellular organelles but intact sarcolemma; grade 2, formation of subsarcolemmal blebs, but overall sarcolemmal integrity; and grade 3, sarcolemmal disruption. In the experiment, grade 1 cells decreased and those of grade 3 increased with a longer period of ischemia. The appearance of grade 3 cells was distinct at 30 min of ischemia. This cellular damage proceeded from the subendocardial layer to the subepicardial layer indicating the "wavefront phenomenon." The number of AMDs within the mitochondria increased as the sarcolemmal damage became more severe. It was noteworthy that AMDs could be found in cells with an intact sarcolemma after subjection to 10 min of ischemia. Myoglobin staining of the myocardium obtained after 10 min of ischemia followed by 6 hr of reperfusion revealed no loss of myoglobin, indicating no irreversible cell damage. This finding suggests that the formation of AMDs may occur prior to the disruption of the sarcolemma or irreversible cell damage. PMID- 2599065 TI - Biology of family systems and mood disorders. AB - Ethology offers psychiatry and family therapy an alternative perspective for understanding hierarchical dysfunction and individual psychopathology and the relation between them. Dominance and submission behaviors--descriptions from ethology--represent communicational mechanisms that play pivotal roles in maintaining the stability of the family group. When conflict becomes acute, dominant and submissive states are experienced as euphoria and mild depression respectively. Smooth functioning of these communicational mechanisms at the individual level enhances cohesion at the group level. Feelings of inadequacy and inferiority may be manifestations of submissive patterns and may function to maintain negative or corrective feedback loops, which preserve group stability. However, these communicational mechanisms may exhibit positive feedback runaway effects such that family crises result. These and other clinical implications of the model are explored. PMID- 2599064 TI - Observations about family interaction and the effect of therapy: interviews with families eight years after the onset of schizophrenia. AB - This study focused on the development of and changes in the interaction within a family after the onset of schizophrenia in a family member. Special attention is given to the possible effects of various treatments on the interaction. Our method was a circular interview of all family members in a joint session 8 years after the onset of schizophrenia. We observed that changes in family interaction usually had taken place during the first year of the illness. Thereafter, family conditions and interactions seem to have remained relatively unchanged. On the other hand, in addition to actual family-centered therapy, all other treatment modes--individual therapy, medication, hospitalization--seemed to have acted as systemic interventions on the family level. Our observation that family interactions and models of therapy often had a surprisingly strong resemblance led us to consider the idea of their coevolution over the years and the possible significance of this. This article aims at calling the reader's attention to the manifold influences that the onset of schizophrenia and its various treatments seem to have had on family system. PMID- 2599066 TI - The "psychosomatic family" model: an empirical and theoretical analysis. AB - Evolution of the Family Systems Paradigm has been constrained by the dichotomy between theory building and empirical research. This article integrates these two domains by presenting a theoretical analysis of the "psychosomatic family" model as it informs and is informed by an empirical research project. Forty families of children with Crohn's disease (CD), ulcerative colitis (UC), and functional recurrent abdominal pain syndrome (RAP) were rated during standard, videotaped family interaction tasks, lunch, and interview. Laboratory scores of disease activity were associated with triangulation, marital dysfunction, and total "psychosomatic family" scores. Disease activity was not significantly correlated with enmeshment, overprotection, rigidity, conflict avoidance, or poor conflict resolution. Thus, the marital/triangulation and enmeshment/overprotection/conflict clusters may be subcomplexes of the "psychosomatic family" complex. CD, UC, and RAP groups differed in the relations among particular family patterns and disease activity. A heuristic family-psycho somatic model is presented to facilitate future research. PMID- 2599067 TI - Outcomes of systemic/strategic team consultation: II. Three-year followup and a theory of "emergent design". AB - This is the second in a series of articles on an experimental, small-sample study of systemic/strategic team consultations. It presents the 3-year outcomes of clients whose 1-month progress was described in an earlier report (12). The 8 therapists in the current study originally were asked to select two ongoing cases matched for difficulty (N = 16). While all cases continued their regular therapy sessions, one of each therapist's two cases were selected at random to participate in a "Milan-informed," five-part team consultation. At 3-year followup, clients who participated in team consultations had maintained significantly higher levels of goal attainment than nonteam clients (p less than .05). For interpreting these results, we propose a developmental theory ("emergent design") to explain therapy impasses, team effects, the impact of termination, and long-range outcomes of therapy. PMID- 2599068 TI - A Piagetian view of family therapy: Selvini-Palazzoli and the Invariant Approach. AB - The Invariant Approach of Mara Selvini-Palazzoli is a new development in the Milan approach to family therapy. In order to distinguish and explain it, an overview of the Invariant Approach is given. Jean Piaget's theory of cognitive development is used to provide a framework for explaining how Selvini-Palazzoli's therapy alters the family's epistemology and facilitates change in the "family game." It is suggested that family members in therapy tend to think about their problems in a style that resembles Piaget's preoperational period. The process of therapy can be seen as geared to facilitate a shift from a preoperational to an operational style of cognitive functioning. This shift gives family members access to more adaptive ways of thinking about their problem-solving strategies. PMID- 2599069 TI - A paradigm for construction of family therapy tasks. AB - Typically, family therapy task interventions involve direct assignment of specific behaviors, which may or may not encourage client compliance. To enhance the clinician's probability of bringing about progress in treatment, this article broadens the parameters of task intervention to include (a) Direct versus Indirect, (b) Behavioral versus Nonbehavioral, and (c) Paradoxical versus Nonparadoxical dimension alternatives. The resulting 2 x 2 x 2 model, the Family Therapy Task Construction Paradigm, yields eight possible choices for end-of-the session punctuation. Each option is linked to corresponding treatment contexts and illustrated with examples from productive case vignettes. PMID- 2599070 TI - [The effect of the synthetic antioxidant emoxypine on the tonus of the coronary vessels]. AB - Intracoronary administration of emoxypine caused the dose-dependent increase in the average coronary blood flow without changing the parameters of cardiohemodynamics. Emoxypine failed to change the structure of the phase coronary blood flow. When administered at the concentration of 5.10(-4)M emoxypine increased the volume rate of the perfusate outflow from the rat isolated heart cavities and decreased the value of potassium contracture of isolated segments of the coronary vessels. The data obtained indicate the direct coronarolytic action of emoxypine. PMID- 2599071 TI - [The effect of dopamine on the systemic hemodynamic indices, on the blood supply of an ischemic focus and on the plasma enzyme activity in dogs with acute coronary occlusion]. AB - In acute experiments on anesthetized dogs dopamine (10 micrograms/kg and 10 micrograms/kg/min) was shown to increase significantly the blood supply to ischemic regions and the minute heart volume at the background of insignificant systemic hypotension and tachycardia. When administered in a dose of 10 micrograms/kg/min dopamine increased the magnitude of the ratio of glycogen phosphorylase b activity to total glycogen-phosphorylase activity in the blood plasma. Administration of 20 micrograms/kg of the drug did not produce a significant increase of the blood supply to ischemic regions and the minute heart volume in the presence of the tendency toward systemic hypotension and bradycardia. PMID- 2599073 TI - [The specific binding of dihydroalprenolol and quinuclidinyl benzilate with myocardial lysosomes]. AB - The binding of 3H-dihydroalprenolol and 3H-quinuclidinyl benzylate to lysosomes of the rat ventricular myocardium vas studied. More than one type of specific binding sites of dihydroalprenolol and quinuclidinyl benzylate at the rat myocardium lysosomes were found. The association constants values differ from the known values of the association constants of the same ligands with plasmatic membranes of the mammalian myocardium. PMID- 2599072 TI - [The cardioprotective action of carnitine and its structural analog 3-(2,2,2 trimethylhydrazine)propionate on cardiac energy metabolism in experimental occlusion of the coronary artery in rats]. AB - The effects of carnitine and its structural analogue 3-(2,2,2-trimethylhydrazine) propionate (THP) were studied in rats with experimental myocardial infarction caused by occlusion of the left descending branch of the coronary artery. After one day in the group of untreated animals the relative lethality was 40.3 +/- 10.5%, the size of the infarction zone was 29.8 +/- 2.0%. Carnitine and THP decreased on the average twice the parameters as well as lactate level in the myocardium. THP prevented a reduction of ATP and AMP levels by 35 and 37%, respectively, and a decrease of adenine nucleotide pool by 30%. In this case carnitine was ineffective. It is suggested that inhibition of beta-oxidation of fatty acids by THP is energetically more beneficial for the myocardium during regional ischemia than substitution therapy with carnitine. PMID- 2599074 TI - [The influence of ciprofloxacin and pefloxacin on blood coagulation and the anticoagulant effect of heparin]. AB - At a single intravenous administration to rabbits ciprofloxacin (10 and 20 mg/kg) and pefloxacin (40 mg/kg) increased the blood coagulability. Administered in a dose of 20 mg/kg pefloxacin exerted no effect on the parameter. Ciprofloxacin (20 mg/kg) and pefloxacin (40 mg/kg) decreased the anticoagulant effect of heparin (100 U/kg). PMID- 2599075 TI - [Mechanisms of the antiaggregation activity of 1,4-naphthoquinone derivatives]. AB - The antiaggregation effects of synthetic derivatives of 1,4-naphtoquinone and ionol were studied as compared with the antioxidant properties of the agents. The proportional relationship was shown to exist between the antiaggregation properties of the compounds and their antiradical activity under conditions of the interaction with biosubstrates. The data obtained suggest that the derivatives of 1,4-naphtoquinone with the intramolecular transfer of the charge are promising antiaggregation agents. PMID- 2599077 TI - [Evaluation of the antiatherosclerotic properties of natural compounds of plant origin on cell cultures of the human aortic intima]. AB - Administration of alizole, berberine, pheonol and pheoniphlorine in doses of 30 100 micrograms/ml in the culture of the atherosclerotic human aortic intimal cells decreased the content of intracellular cholesterol by 35-41% and reduced the proliferative activity of the cells. In healthy donors administration of single doses of berberine and pheoniphlorine (0.9 g) increased the antiatherogenic potential of the serum which was estimated on the primary culture of the intimal cells. PMID- 2599078 TI - [The effect of folic acid and methotrexate on the activity of the glucuronyl- and glutathione-conjugating systems of the liver in rats]. AB - Administration to intact male rats of folic acid (25 mg/kg intragastrically for 14 days) was shown to increase and that of methotrexate (0.5 mg/kg subcutaneously) for 14 days) to decrease the activities of the rat liver uridine diphosphate-glucuronosyl- and glutathione-S-transferases. PMID- 2599076 TI - [The antihypoxic activity of endogenous cyclic derivatives of gamma-aminobutyric acid]. AB - Pirrolidone-2, gamma-butyrolacton, succinic anhydride were found to possess pronounced antihypoxic activity that manifested itself in their ability to decrease the level of lactic acid accumulated during hypoxia. Pirrolidone-2 and succinic anhydride increase succinic dehydrogenase activity in vitro. At intraperitoneal administration the above mentioned compounds lead to lactate dehydrogenase activity inhibition under normal conditions while during circulatory hypoxia they stimulate lactate dehydrogenase reaction promoting the maintenance of energy balance of the cerebral tissue at the appropriate level. PMID- 2599079 TI - [Lipid peroxidation in the liver of dogs and guinea pigs receiving chloditan]. AB - The contents and the rates of the formation of lipid peroxides in the liver homogenates were studied. Dogs and guinea pigs were fed with chloditan in doses of 50 and 150 mg/kg body weight, respectively, for 20 days. In the dogs chloditan caused atrophy of the adrenal glands. The drug accumulation in the adrenal glands of the guinea pigs did not produce damage of the glands. The feeding with chloditan failed to change the level of malondialdehyde in the livers of the dogs and decreased it in the livers of the guinea pigs. In vitro spontaneous and NADP N-dependent lipid peroxidation in the liver homogenates of the dogs treated with chloditan was slowed. The decrease of malondialdehyde content in the guinea pig liver and the slowing of lipid peroxidation rate in the dog liver homogenate can be explained by the change in the activity of the enzymes detoxicating xenobiotics and products of lipid peroxidation. PMID- 2599080 TI - [The effect of furanocoumarins on microsomal oxidation in the rat liver]. AB - Puvalen and psoberan are inhibitors of monoxygenase enzyme system activity of the liver. Puvalen exerts the biphase effect on the system, so it may be referred to such classic inhibitors as SKF-525A and pyperonil butoxide. Psoberan does not exert the biphase effect on the monoxygenase system that is apparently connected with its negative action on biomembrane structure of hepatocytes. The results must be taken into consideration when patients are treated with psoralens. PMID- 2599082 TI - [The pharmacokinetics of theopek--a new Soviet prolonged-action drug form of theophylline--in patients with bronchial asthma]. AB - Pharmacokinetics of theopek--a new original slow release formulation of theophylline--as compared with theotard and theodur was studied in patients with bronchial asthma. The pharmacokinetic parameters of this product were shown to be comparable. A significant correlation between blood theophylline concentration and the bronchodilating and diuretic effects in patients with bronchial asthma was revealed. PMID- 2599083 TI - [The pharmacokinetics and the concentration-and-effect relationship of prazosin in patients at the beginning of the subacute period of myocardial infarct complicated by the development of heart failure]. AB - The pharmacokinetics of prazosin was studied in 16 patients in the early subacute period of myocardial infarction complicated with heart failure following a single and 10-day administration. The increase of the half-life of the drug (6.6 +/- 1.6 h) and the elevation of the blood plasma concentration 1-2.5 h after administration (87 +/- 33 ng/ml) were found. After 10-day administration the increase of the apparent total clearance of the drug was established. The blood plasma levels of prazosin significantly correlated with the change of the hemodynamic parameters measured invasively after a single administration of 2-5 mg of the drug. After 10 days of treatment the correlation weakened and the regression line angle reduced that reflected the development of tolerance to the drug. On the basis of the calculated effective concentrations, there were determined the optimal intervals of the drug dosage. PMID- 2599081 TI - [Characteristics of enzyme induction in the liver monooxygenase system of rabbits intravenously administered a fluorocarbon emulsion]. AB - Intravenous injections to rabbits of perfluorocarbon emulsion containing perfluorodecaline (10 ml/kg, equivalent to 1.3 g of perfluorodecaline per 1 kg of body weight) produced a 2-4-fold increase of cytochrome P-450 content in the liver microsomes within 3-4 weeks. Cytochrome P-450 induction was followed by activation of the liver monoxygenase system evaluated by the rate of antipyrine excretion from the blood. On the 1st day after administration perfluorodecaline caused an insignificant (14%) inhibition of the monoxygenase system. PMID- 2599084 TI - [The effect of anaprilin (obzidan) on adrenergic-dependent adaptive reactions of the body under conditions of prolonged stress exposure]. AB - The conditions of some biochemical and functional systems of the rat organisms at daily intramuscular injections of obsidan (0.05 mg/100 g body weight) for one month were studied to evaluate the effect of obsidan on the adrenergic-dependent adaptive reactions. It was shown that the procedure of injections itself (the control group of animals receiving injections of sodium chloride isotonic solution) is stress leading to a decrease of beta-adrenergic-dependent reactions and an increase of alpha-adrenergic-dependent ones. The combination of this stress with the pharmacological effect of obsidan is characterized by a decrease of adrenaline release in blood, a reduction of manifestations of alpha-adrenergic reactions, a decline of lipid energy substrates consumption level. PMID- 2599085 TI - Expression of mRNAs for collagens and other matrix components in dedifferentiating and redifferentiating human chondrocytes in culture. AB - Cell cultures were initiated from epiphyseal cartilages, diaphyseal periosteum, and muscle of 16-week human fetuses. Total RNAs isolated from these cultures were analyzed for the levels of mRNAs for major fibrillar collagens, two proteoglycan core proteins and osteonectin. In standard monolayer cultures the differentiated chondrocyte phenotype was replaced by a dedifferentiated one: the mRNA levels of cartilage-specific type II collagen decreased upon subculturing, while those of types I and III collagen, and the core proteins increased. When the cells were transferred to grow in agarose, redifferentiation (reappearance of type II collagen mRNA) occurred. Fibroblasts grown from periosteum and muscle were found to contain mRNAs for types I and III collagen and proteoglycan cores. When these cells were transferred to agarose they acquired a shape indistinguishable from chondrocytes, but no type II collagen mRNA was observed. PMID- 2599087 TI - A special repressor/activator system controls distribution of mRNA between translationally active and inactive mRNPs in rabbit reticulocytes. AB - Translation of free mRNPs and polyribosomal mRNPs from rabbit reticulocytes was studied in a rabbit reticulocyte and wheat germ cell-free systems. It has been shown that translation efficiency of polyribosomal mRNPs and the mRNA isolated from the particles is nearly the same in both systems. At the same time, mRNP's translatability, which is high in the homologous cell-free system, is very low in the system from wheat germs. Translation efficiency of free mRNPs in the wheat germ system can be restored by addition of 0.5 M K CI-wash of rabbit reticulocyte ribosomes. The results testify to the existence of some special repressor repressor/activator system which controls the distribution of mRNA between free mRNPs and polyribosomes in rabbit reticulocytes. PMID- 2599086 TI - A cysteine proteinase cDNA from Trypanosoma brucei predicts an enzyme with an unusual C-terminal extension. AB - A cDNA for a Trypanosoma brucei cysteine proteinase has been cloned and sequenced. The deduced protein can be divided into four domains, based on homologies with other cysteine proteinases: the pre-, pro- and central regions show considerable homology to the cathepsin L class of mammalian enzymes, whilst the long C-terminal extension distinguishes the trypanosome enzyme from all mammalian cysteine proteinases reported. This 108 amino acid extension, which includes 9 contiguous prolines near the junction with the central domain, appears likely to be processed in part to produce the mature enzyme, and may be involved in targeting the protein within the cell. The trypanosome genome contains more than 20 copies of the cysteine proteinase gene arranged in a long tandem array. PMID- 2599088 TI - Biosynthesis of small proteoglycans by hepatic lipocytes in primary culture. AB - Chondroitin sulfate/dermatan sulfate proteoglycans were obtained from the secretions of cultured rat hepatic lipocytes. The collagen-binding small proteoglycan II represented only a minor species (less than 10%), whereas similar amounts of small proteoglycan I and of a novel collagen-binding proteoglycan with a core protein of 101 kDa were found. These results support the concept of a special role of lipocytes in the pathogenesis of liver fibrosis. PMID- 2599089 TI - Purification to homogeneity and characterization of major fatty acid ethyl ester synthase from human myocardium. AB - Non-oxidative metabolism of ethanol via fatty acid ethyl ester synthase is present in those extrahepatic organs most commonly damaged by alcohol abuse. DEAE cellulose chromatography of human myocardial cytosol at pH 8.0 separated synthase I, minor and major activities, eluting at conductivities of 5, 7 and 11 mS, respectively. The major synthase was purified 8900-fold to homogeneity by sequential gel permeation, hydrophobic interaction, and anti-human albumin affinity-chromatographies with an overall yield of 25%. SDS-PAGE showed a single polypeptide with a molecular mass of 26 kDa and gel permeation chromatography under nondenaturing conditions indicated a molecular mass of 54 kDa for the active enzyme. The purified enzyme catalyzed ethyl ester synthesis at the highest rates with unsaturated octadecanoic fatty acid substrates (Vmax = 100 and 65 nmol/mg/h for oleate and linoleate, respectively). Km values for oleate, linoleate, arachidonate, palmitate and stearate were 0.22 mM, 0.20 mM, 0.13 mM, 0.18 mM and 0.12 mM, respectively. Thus, human heart fatty acid ethyl ester synthase (major form) is a soluble dimeric enzyme comprised or two identical, or nearly identical, subunits (Mr = 26000). PMID- 2599090 TI - Immunological detection of arrestin, a phototransduction regulatory protein, in the cytosol of nucleated erythrocytes. AB - Cytosolic extracts of trout and turkey erythrocytes were tested for their immunoreactivity with polyclonal and monoclonal antibodies to retinal arrestin (S antigen), a cytosolic protein of photoreceptor cells involved in the desensitization of rhodopsin. After adsorption or immunoaffinity chromatography of the extracts, these antibodies specifically recognized a protein having a molecular weight similar to that of retinal arrestin. Because the G-protein mediated transduction systems, such as visual and beta-adrenergic systems, display a high degree of structural and functional homology, the presence of arrestin-like proteins in non-photosensitive cells suggests that these proteins are involved in the transduction of chemical signals, with a possible role in receptor desensitization. PMID- 2599091 TI - New reagent for discrimination of single- and double-stranded regions in DNA. AB - It was found that DNA alkylation at the N-7 guanine with the bulky alkylating reagent, N,N,N'-tri-(beta-chloroethyl)-N'-(p-formylphenyl)propylene diamine-1,3 (TFP) is much diminished when DNA is double-stranded. We report here an application of this reaction for probing the hairpin structure in the palindrome containing single-stranded (ss) DNA fragment of 377 bases prepared from the Eco RI-BaMHI fragment of plasmid pBR322. 5'-Labeled ss fragment was modified with TFP and cleaved by piperidine hydrolysis at the alkylated guanine residues according to the Maxam-Gilbert procedure. Guanines in the hairpin formed by palindrome of 9 bp were protected from TFP action, while dimethyl sulfate modified all guanines. PMID- 2599092 TI - Sheep neuropeptide Y. A third structural type of a highly conserved peptide. AB - Mammalian forms of neuropeptide Y (NPY) for which the amino acid sequences have previously been determined, are the human, pig, ox, rabbit, rat, and guinea-pig polypeptides. The only difference among these forms is at position 17, where pig and ox NPY have Leu and the others Met. We now show that sheep NPY differs from all the earlier characterized mammalian forms of NPY by having Asp instead of Glu at position 10. At position 17 it has Leu as do both pig and ox NPY. Consequently, 3 different structural types of mammalian NPY are now known. PMID- 2599093 TI - Interleukin 1 and tumour necrosis factor increase phosphorylation of the small heat shock protein. Effects in fibroblasts, Hep G2 and U937 cells. AB - Interleukin 1 alpha and tumour necrosis factor-alpha stimulated phosphorylation of three 27 kDa phosphoproteins in MRC-5 fibroblasts which was sustained for up to 2 h after adding the cytokines. All three phosphoproteins were immunoprecipitated by a specific antiserum to the small mammalian heat shock protein, hsp 27. The three phosphoproteins from stimulated or control cells contained phosphoserine but not phosphothreonine or phosphotyrosine. Similar increases in phosphorylation of immunoprecipitable 27 kDa proteins were seen in U937 cells stimulated by TNF alpha and Hep G2 cells stimulated by IL1 alpha. PMID- 2599094 TI - Additive effects of dexamethasone and calcium on the calcitonin mRNA level in adrenalectomized rats. AB - Northern hybridizations were used to evaluate the effects of dexamathasone and calcium on calcitonin mRNA levels in adrenalectomized female rats. Two weeks after adrenalectomy, a 3.6-fold decrease in the calcitonin mRNA level was observed (28% vs 100% in sham-operated controls). After 5 days of dexamethasone treatment (1.5 mg/kg b. wt), a 2.6-fold rise in calcitonin mRNA occurred in adrenalectomized rats (73% vs 28%). This increment was higher when dexamethasone treated animals were injected with calcium (100% vs 73%). The effect of calcium on the calcitonin mRNA level of adrenalectomized rats treated or not with dexamethasone was similar, and additive in the former case. Our data suggest that calcium and dexamethasone elevate calcitonin mRNA by two different mechanisms. PMID- 2599095 TI - An ice nucleation active gene of Erwinia ananas. Sequence similarity to those of Pseudomonas species and regions required for ice nucleation activity. AB - The ice nucleation active gene, inaA, of Erwinia ananas IN-10 has been sequenced. This gene encodes a protein composed of 1322 amino acid residues. The inaA protein contains a 1120-residue segment consisting of 70 repeats of closely related 16 amino acid motifs (R-domain), which is flanked by N- and C-terminal sequences (N- and C-domains, respectively). Its primary structure is similar to, but not identical with, those of Pseudomonas inaW and inaZ gene products. By truncating the inaA gene to various extents, it was found that deletion of the C domain resulted in complete loss of the ice nucleation activity, whereas removal of the N-domain led to a moderate decrease in the activity. Complete loss of the activity was also observed when the N-domain plus a large part of the P-domain were deleted. It is suggested that the C-domain is required for the assembly of inaA protein to form a functional ice nucleus. PMID- 2599096 TI - Constitutive in vitro binding of nuclear proteins to the 5'-flanking region of 6 16, a human gene inducible by alpha, beta-interferons. AB - Proteins in nuclear extracts of HeLa cells that constitutively bound in vitro to three regions upstream of the interferon-inducible gene 6-16 were separated partially by chromatography on DEAE-Sepharose. Region one, a CCAAT box in the non coding strand at position --63 to --67, was protected from DNase digestion by the bound protein(s) and was required for transcription in vitro. Region two, a tandem duplication sequence at position --89 to --168 contains two copies of a sequence essential for strong induction of the 6-16 gene by interferon in vitro. Region three, a palindromic sequence at position --449 to --465, not necessary for induction of 6-16 by interferon, was also protected from DNase digestion by nuclear protein(s). Templates with or without regions of two and three were transcribed equally well in extracts from interferon-treated or untreated cells. PMID- 2599097 TI - The neuroleptic activity of haloperidol increases after its solubilization in surfactant micelles. Micelles as microcontainers for drug targeting. AB - It has been suggested to use surfactant micelles as microcontainers for increasing the efficiency of neuroleptic targeting from blood flow into the brain. The neuroleptic action of haloperidol, intraperitoneally injected into mice in micellar solution of non-ionic block copolymer surfactant (pluronic P-85) in water, increased several-fold if compared with that observed for haloperidol aqueous solution. Incorporation of brain-specific antibodies into haloperidol containing micelles resulted in additional drastic increase (more than by 2 orders of magnitude) in the drug effect. PMID- 2599098 TI - Identification of induced protein kinase activities specific for the ribosomal proteins uniquely phosphorylated during infection of HeLa cells with vaccinia virus. AB - We have examined the ribosomal protein kinase activities in partially purified cytoplasmic extracts from HeLa cells infected with vaccinia virus. We found an activity or activities, absent from mock-infected cells, that was capable of phosphorylating the proteins S2 and S13 in vitro. The ribosomes phosphorylated in vitro exhibited the same multiple phosphorylation of S2 found in vivo, at least 3 phosphoryl residues being seen, and the same mono-phosphorylation of S13. Also as in vivo, ribosomal protein S2 contained phosphothreonine as well as phosphoserine, whereas S13 contained only phosphoserine. This strongly suggests that these new protein kinase activities are responsible for the ribosomal protein phosphorylations that occur during infection with vaccinia virus. PMID- 2599099 TI - Scapharca hemoglobins, type cases of a novel mode of chain assembly and heme-heme communication. Amino acid sequence and subunit interactions of the tetrameric component. AB - The sequences of the A and B chains of the Scapharca inaequivalvis tetrameric hemoglobin (HbII) are reported. They are homologous to the corresponding chains of other Arcid hemoglobins. Moreover, a comparison of the present data with the sequence of the S. inaequivalvis dimeric hemoglobin (HbI), for which high resolution X-ray data are available, allows the identification of the residues that direct the assembly of the two components and of those that may be involved in the interdimeric contacts. PMID- 2599100 TI - Utilization of alanine for glucose formation in isolated rabbit kidney-cortex tubules. AB - In kidney cortex tubules isolated from fed rabbits L-alanine is not utilized as glucose precursor, when added as a sole substrate. However, this amino acid decreases gluconeogenesis from low (up to 1 mM) 2-oxoglutarate concentrations and stimulates this process at higher (2.5-10 mM) ketoacid contents in the suspension medium. Aminooxyacetate, an inhibitor of aminotransferases, abolishes both inhibitory and stimulatory effects of L-alanine on glucose formation. The addition of 2-oxoglutarate increases the incorporation of L-[U-14C]alanine to glucose from 8- to 123-fold, depending upon the ketoacid and alanine concentrations used. In contrast, nonlabelled L-alanine decreases the incorporation of low [U-14C)2-oxoglutarate concentrations into glucose, while it does not affect contribution of 5 mM ketoacid to gluconeogenesis. The data indicate that (i) in the presence of 2-oxoglutarate L-alanine is utilized as glucose precursor in rabbit renal tubules and (ii) this amino acid may decrease the contribution of low extracellular concentrations of the ketoacid to gluconeogenesis. PMID- 2599101 TI - Surfactant enhancement of polyethyleneglycol-induced cell fusion. AB - B16 mouse melanoma cells in monolayers may be satisfactorily fused with 50% PEG 1500. However, pre-treatment with detergents in solution at low concentrations significantly increases PEG fusion, up to 8-fold in some instances, without impairing cell viability. The practical and mechanistical implications of this finding are discussed. PMID- 2599102 TI - Molecular cloning, cDNA structure and predicted amino acid sequence of bovine 3 beta-hydroxy-5-ene steroid dehydrogenase/delta 5-delta 4 isomerase. AB - We have used our recently characterized human 3 beta-hydroxy-5-ene steroid dehydrogenase/delta 5-delta 4-isomerase (3 beta-HSD) cDNA as probe to isolate cDNAs encoding bovine 3 beta-HSD from a bovine ovary lambda gtll cDNA library. Nucleotide sequence analysis of two overlapping cDNA clones of 1362 bp and 1536 bp in length predicts a protein of 372 amino acids with a calculated molecular mass of 42,093 (excluding the first Met). The deduced amino acid sequence of bovine 3 beta-HSD displays 79% homology with human 3 beta-HSD while the nucleotide sequence of the coding region shares 82% interspecies similarity. Hybridization of cloned cDNAs to bovine ovary poly(A)+ RNA shows the presence of an approximately 1.7 kb mRNA species. PMID- 2599103 TI - Limited proteolysis of C1-inhibitor by chymotrypsin-like proteinases. AB - Limited proteolysis of C1-inhibitor was observed with human skin chymase, human cathepsin G, and bovine chymotrypsin. In each case, the inhibitor was degraded to one major product migrating slightly faster than the native inhibitor in an SDS polyacrylamide gel. The inhibitory activity of C1-inhibitor against human plasma kallikrein was not altered by the modification with chymase. Edman degradation of the proteolyzed inhibitor revealed two sequences in a 1:1 ratio: NPNATSSSQ, the N terminus of native C1-inhibitor, and VEPILEVSSL. This second sequence showed that the Phe33-Val34 bond was hydrolyzed. Our results provide another example of the susceptibility of the N-terminal region of C1-inhibitor to proteolytic cleavage. PMID- 2599104 TI - S-phase inhibitors induce vimentin expression in human promonocytic U-937 cells. AB - The administration of hydroxyurea (3 x 10(-4) M) and cytosine arabinoside (10(-7) M) greatly induces the expression of the vimentin gene in human promonocytic leukemia U-937 cells. The induction takes place at both the mRNA and protein levels, as demonstrated by Northern blot, immunoblot and immunofluorescence assays. On the contrary, the drugs inhibit the expression of c-myc and ornithine decarboxylase, and do not modify significantly the expression of beta-actin. Since hydroxyurea and cytosine arabinoside trigger the phenotypic differentiation of U-937 cells, as demonstrated by the induction of the differentiation-specific CD11b and CD11c antigens, it is concluded that vimentin expression might be implicated in the maturation of these cells. PMID- 2599105 TI - Establishment of mouse and rat hepatoma cell clones showing stable expression of rabbit cytochrome P450 IA2. AB - Cytochrome P450 IA2, a liver-specific member of the 3-methylcholanthrene inducible family, is never detected in established cell lines. With the aim of isolating cells stably producing this protein, we have used rat and mouse hepatoma cells as recipients in transfection experiments involving rabbit cytochrome P450 IA2 cDNA. We report here the isolation of five hepatoma cell clones expressing functional P450 IA2. The level of expression is comparable to that found in COS cells transiently transformed by other P450 cDNAs. It ranges between 0.4 and 1.6 pmol P450 IA2/mg total cell protein. PMID- 2599106 TI - A lateral cap model of microtubule dynamic instability. AB - The co-existence and interconversion of growing and shrinking microtubules have been termed 'dynamic instability,' and have been directly observed to occur under a variety of conditions in vitro and in vivo. Previous modeling was based on the concept of an extensive, fluctuating cap of tubulin-GTP to stabilise growing microtubules. A quantitative kinetic model is now presented in which only the terminal layer of the multi-start helical microtubule lattice contains tubulin GTP molecules, comprising a 'Lateral Cap.' In Monte Carlo numerical simulation, this model readily produces the decisive experimental evidence of microtubule dynamics, and predicts a co-operative mechanism for microtubule transitions. The model also suggests how differing kinetic properties at opposite ends are the result of the intrinsic polarity of the microtubule lattice, reflecting the polarity of the tubulin alpha/beta heterodimer. PMID- 2599107 TI - Rapid actions of 1 alpha,25-dihydroxyvitamin D3 on Ca2+ and phospholipids in isolated rat liver nuclei. AB - The effects of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) on Ca2+ levels and phospholipid metabolism were studied in isolated nuclei prepared from rat liver. Nuclear Ca2+ concentration was estimated with the fluorescent indicator Fura 2. In agreement with previous reports, ATP (1 mM) produced a rapid increase in nuclear Ca2+ from 188 +/- 25 to 593 +/- 121 nM. Exposure to 1 alpha,25-(OH)2D3 (20 nM) also produced a rapid increase in nuclear Ca2+ to 402 +/- 71 nM. The 1 beta epimer of 1 alpha,25-(OH)2D3 had no effect. Nuclear phosphatidylinositol was labeled by incubation with [gamma-32P]ATP for 3 h. 1 alpha,25-(OH)2D3 produced a two-fold increase in [32P]lysophosphatidylinositol (LPI) within 5 min from 44 +/- 11 to 87 +/- 19 cpm/2.5 x 10(7) nuclei. 1 beta,25-(OH)2D3 had no effect on [32P]LPI production. Exposure of nuclei to exogenous LPI (15 microM) produced an instantaneous increase in nuclear Ca2+ to 372 +/- 81 nM, comparable to ATP and 1 alpha,25-(OH)2D3. The rapid effects of 1 alpha,25-(OH)2D3 on phospholipid metabolism and Ca2+ in isolated nuclei suggest that the steroid may exert effects distinct from the well-characterized receptor-mediated changes in gene expression. PMID- 2599108 TI - Platelet-activating factor (PAF) acts as an intercellular messenger in the changes of cytosolic free Ca2+ in human neutrophils induced by opsonized particles. AB - Addition of opsonized particles to human neutrophils in suspension leads to a biphasic elevation in the cytosolic free Ca2+ concentration ([Ca2+]i). The rise in [Ca2+]i during the second phase (greater than 3 min) is pronounced (about 400 nM), in contrast to the rise during the first phase, which is relatively small (less than 100 nM). The second and large rise in [Ca2+]i is brought about by messenger(s) released from the cell after addition of opsonized particles. This second rise in [Ca2+]i is not observed in the presence of the platelet-activating factor (PAF) antagonist WEB 2086, indicating that PAF can act as an intercellular messenger affecting Ca2+ homeostasis in human neutrophils. PMID- 2599109 TI - Potassium channels from NG108-15 neuroblastoma-glioma hybrid cells. Primary structure and functional expression from cDNAs. AB - The complete amino acid sequences of two potassium channel proteins from NG108-15 neuroblastoma-glioma hybrid cells have been deduced by cloning and sequencing the cDNAs. One of these proteins (NGK2) is structurally more closely related to the Drosophila Shaw gene product than to the Shaker and Shab gene products, whereas the other (NGK1) is identical with a rat brain potassium channel protein (BK2) which is more closely related to the Drosophila Shaker gene product. mRNAs derived from both the cloned cDNAs, when injected into Xenopus oocytes, direct the formation of functional potassium channels with properties of delayed rectifiers. PMID- 2599110 TI - The hexose carrier from Chlorella. cDNA cloning of a eucaryotic H+-cotransporter. AB - The cDNA coding for the inducible H+/hexose cotransporter of Chlorella kessleri has been cloned and sequenced. It was isolated by differential screening of a cDNA library prepared from glucose-induced cells. The increase in expression of the gene correlates quantitatively with the increase in uptake activity due to induction; it is not expressed in a hexose transport mutant. An open reading frame allows for a membrane protein of 533 amino acids with a relative molecular mass of 57 kDa. This protein is highly homologous to the human and rat glucose transporters catalyzing facilitated diffusion and to the bacterial H+/pentose cotransporters. It is not related to the H+/lactose cotransporter of E. colli and to the mammalian Na+/glucose cotransporter. PMID- 2599111 TI - The in vivo phosphorylation sites of bovine alpha B-crystallin. AB - Phosphate content determinations established that in alpha B-crystallin two phosphate groups can be present in vivo in bovine lenses. Comparison of tryptic digests of phosphorylated and unphosphorylated alpha B chains, revealed the location of the two phosphorylation sites in tryptic peptides T2 and T3. Thermolytic digestion and gas-phase sequencing demonstrated that Ser-19 and Ser 45 are the in vivo phosphorylation sites of bovine alpha B-crystallin. This pattern of phosphorylation differs from the previously reported in vitro obtained results. PMID- 2599112 TI - Phospholipase D activation by the mitogens platelet-derived growth factor and 12 O-tetradecanoylphorbol 13-acetate in NIH-3T3 cells. AB - The effect of mitogens on phospholipase D activity was investigated in NIH-3T3 fibroblasts by measuring the accumulation of phosphatidylpropanol, produced by phospholipase D phosphatidyl transferase activity when 1-propanol acts as the phosphatidyl group acceptor. Platelet-derived growth factor (PDGF) and 12-O tetradecanoylphorbol 13-acetate (TPA) stimulated phosphatidylpropanol production by the cells. The dose-response relationships for activation of phospholipase D and stimulation of thymidine incorporation by PDGF and TPA were comparable. The possibility that activation of phospholipase D is utilized by mitogens as a trans membrane pathway for signalling cell growth is discussed. PMID- 2599113 TI - Gene structure and 5'-upstream sequence of rat cathepsin L. AB - The structure of rat cathepsin L gene has been determined. The gene spans 8.5 kilobase pairs comprising 8 exons, and has an intron located near the active site cysteine residue. The gene structure does not correspond well to the functional units of the proteinase. These characteristics are found to be in common with the cysteine proteinase gene family. In the 5'-upstream region, one CAAT-box and four SP-1 binding sites, together with two AP-2 binding sites and CRE, but no typical TATA-box are found. Further, SP-1 and AP-2 binding sites and an octamer motif are also found in the 1st intron, suggesting a complex regulatory mechanism for the expression of the cathepsin L gene. PMID- 2599114 TI - A synthetic peptide substrate specific for casein kinase I. AB - The synthetic peptide, Asp-Asp-Asp-Glu-Glu-Ser-Ile-Thr-Arg-Arg, derived from the phosphorylation site of casein kinase-1 (CK-1) in beta-casein A(2), is readily phosphorylated by CK-1, but not by casein kinase-2(CK-2), cyclic AMP-dependent protein kinase, protein kinase C, phosphorylase kinase and protein kinase FA. Phosphorylation by CK-1 occurs only at Ser-6, Thr-8 being unaffected. The Km for the peptide is higher (1 mM) than for beta-casein A(2) (40 microM), while the Vmax is quite comparable. This is the first synthetic peptide substrate for CK-1 described so far, and can be used for the rapid and specific estimation of CK-1 activity in crude extracts. PMID- 2599116 TI - Indoor air quality: organic pollutants. Report on a WHO meeting. PMID- 2599115 TI - Evidence for leukotriene C4 transport mediated by an ATP-dependent glutathione S conjugate carrier in rat heart and liver plasma membranes. AB - Using rat heart sarcolemma and liver plasma membrane vesicles, it has been verified that the transport of leukotriene C4 (LTC4) across membranes is an ATP dependent process; the apparent Km for LTC4 was 150 nM (heart sarcolemma) or 250 nM (liver plasma membrane). S-(2,4-dinitrophenyl)-glutathione (DNP-SG) inhibited LTC4 uptake into the vesicles dose-dependently (I50 = 25 microM for both heart sarcolemma and liver plasma membrane vesicles). Mutual inhibition between LTC4 and DNP-SG in uptake into the vesicles demonstrates that transport of LTC4 is mediated by an ATP-dependent glutathione S-conjugate carrier. PMID- 2599117 TI - Specialized medical education in the European Region. EURO Reports and Studies 112. PMID- 2599118 TI - Local postoperative morbidity following pre-operative irradiation in locally advanced breast cancer. AB - The authors have reviewed the medical files of 100 patients with locally advanced breast cancer (Stage III), who were treated in the Department of Surgery at the Institut Jules Bordet between 1974 and 1988. All patients received pre-operative radiotherapy (average total dose 45 Gy), which was associated with chemotherapy in 74% of patients. All patients were subsequently subjected to surgery, using a modified mastectomy in 92% of cases. Our data reveal an incidence of 25% local wound infection, 34% delayed wound healing, 63% seroma formation and 22% lymphoedema of the upper limb. It seems that local postoperative morbidity is increased in patients pre-operatively irradiated. This indicates that pre operative chemotherapy may be preferable in these patients to minimize the local postoperative morbidity and its impact on the quality of life. PMID- 2599120 TI - Upper extremity function after conservative interscapulo-thoracic tumor resection. AB - Six patients who had undergone an en bloc interscapulo-thoracic excision (for primary bone or soft tissue sarcoma in five, and metastatic disease in one) were subject to review, with special emphasis on the functional outcome of the operated arm. Active shoulder motion was poor in all patients, but this did not prevent passive positioning of the hand and elbow. Elbow and particularly hand function was either not, or only slightly, impaired so that two patients regained full use of their upper extremity. Three patients had satisfactory but impaired function and one with metastatic disease of the should had a poor functional outcome. PMID- 2599119 TI - Axillary dissection in breast cancer revisited. AB - The pathological status of the axillary nodes remains the single most determining factor for survival, local recurrence and disease-free interval in operable breast cancer. Radical axillary dissection results in better local control with or without systemic disease in all operable cases. In pathologically negative cases, radical axillary dissection decreases local recurrence rates and perhaps prolongs disease-free survival. In pathologically positive cases, radical axillary dissection improves local control only. Radical axillary dissection avoids axillary irradiation and so decreases the risk and the importance of lymphoedema. Perfect axillary dissection does not show a decisive advantage over less complete axillary dissection when the 'quality' of surgery is measured by lymphoscintigraphy, but it should be kept in mind that only total control of the local situation can ensure a patient free of distal spread at the time of first therapy. PMID- 2599121 TI - Results of 206 isolated limb perfusions for malignant melanoma. AB - Between 1976 and 1988, 182 patients--135 females (74.3%) and 47 males (25.7%)- were submitted to 206 isolation perfusions, using melphalan and mild hyperthermia for 34 upper and 172 lower limbs. Stage I melanoma represented 37.4% including 75.4% greater than 1.5 mm Breslow thickness or with regression, ulceration or incisional biopsy. Stage II melanoma included 62.6% of the cases. Peri-operative mortality occurred in 2/182 patients. Amputation was performed within 1 month for toxic reasons in three patients and delayed in six for progressive disease. Regional toxicity consisted in oedema (76%), pain (61%), nerve palsy (24%), thrombosis (7%), septicemia (3%), thrombocyto-granulopenia (1.5%), minor miscellaneous (52%). Mean peripheral leakage was 1.0, 7.8 and 12.4% at respectively 5, 10 and 60 minutes. Projected 5-year disease-free survival was 79% for Stage I and 27% for Stage II. Survival at 5 years was 92% in Stage I and 53.5% in Stage II. Twenty-five patients were perfused twice for recurrence or incomplete response. Although the median disease-free interval was only about 8 months, the 5-year survival was 67%. This may indicate that isolation perfusion renders melanoma metastases less aggressive despite the fact they may recur at a high rate. PMID- 2599122 TI - Surgical treatment of bone metastases of the peripheral skeleton--a review of 33 cases. AB - Out of a total of 31 patients (26 females and five males) there were 24 complete and nine impending pathological fractures. These, treated from October 1985 to September 1987 at the Bordet Institute, were evaluated. Breast cancer was the most frequent underlying disease (66%) followed by lung cancer (12%). Eighteen lesions were treated by endoprosthetic replacement and 15 by an intramedullary fixation device. Bone cement was added to either of these. Satisfactory pain relief was obtained in 82% of the treated areas and restoration of function in 76%. Complications were rare but included one easily resolved superficial wound infection, four deep venous thromboses, movement limited to 21% (seven joints), and the changing of two fixation or reconstruction devices. Median survival time was 6 months; 35% of the patients were still alive after 12 months and 10% after 24 months. PMID- 2599123 TI - Resection of lung metastases from sarcomas. AB - Between 1977 and 1987, 19 patients were candidates for resection of lung metastases from pretreated extrathoracic primary tumours. Primary tumours comprised 10 osteosarcomas, one Ewing sarcoma and eight soft tissue sarcomas. All 19 patients presented with metachronous metastases. Twenty-eight thoracotomies were performed in these 19 patients. Nine patients underwent multiple surgical explorations. All the metastases were removed by wedge resection. Seven out of 10 patients treated for osteosarcoma received pre- and postoperative chemotherapy, and three out of 10 postoperative chemotherapy only. The projected survival rate at 3 years is 33%. Seven out of 19 patients survived more than 2 years; four of them were free of disease at 33, 54, 56 and 137 months. Good prognosis appears to be long metastases-doubling time, metachronous metastases, small number of lung metastases, pathological evidence of tumour necrosis and/or fibrosis after chemotherapy and, of course, complete control of the primary tumour and no extrathoracic metastases. PMID- 2599124 TI - Local excision as conservative treatment for small rectal cancer. AB - Twenty patients with small rectal cancer, characterized by a well differentiated tumour localized within 10 cm of the anal margin, and by penetration limited to the submucosa or to the muscular layer, were treated by local excision. Four of them, who presented with a deep tumour invasion in the rectal wall, also received adjuvant radiation therapy. Our experience proves the reliability of the selection criteria for patients who may benefit from this procedure. They all stand a fair chance of cure and the quality of their lives will improve because local tumour excision avoids anal sphincter resection. Two patients had local recurrences and had to undergo further curative local excision. The two who died from their tumours and who had distant metastases were unsuitable for both local resection and other therapeutic procedure. Finally, there was no postoperative morbidity. PMID- 2599125 TI - Prolonged venous access in cancer patients. AB - One hundred and forty-eight Hickman-Broviac (HB) catheters and 299 Port-a-Cath R (PAC) were inserted over the past 5 years at the Institut Jules Bordet. The HB catheter was associated with a complication rate of 4.1/1000 days of access, of which infections were the most common, leading to catheter removal in 22% of patients. The average PAC remained in situ for 232.9 (range 1-1298) days; the complication rate was only 0.45/1000 days of access. The Hickman-Broviac catheter and the totally implanted port Port-a-Cath achieve safe and reliable venous access in cancer patients. PMID- 2599126 TI - Vertical hemipharyngolaryngectomy: reconstruction with the radial forearm free flap. AB - A considerable body of literature defines techniques to restore glottic function after partial laryngectomy. The authors of this paper describe a new original technique for glottic and hypopharyngeal reconstruction after vertical hemipharyngolaryngectomy. Using a radial forearm free flap including the tendon of the palmaris longus and a sensitive branch of the radial nerve, they were able to reconstruct the missing vocal cord and a pyriform fossa. This procedure permits an extended resection without the usual phonatory or swallowing inconveniences. There is no contraindication for postoperative radiotherapy. The technique and preliminary functional results are reported. PMID- 2599127 TI - Free and pedicled flaps for head and neck reconstruction in radically irradiated fields: 6 years' experience at the Jules Bordet Institute. AB - From 1982 to 1988, 127 flaps were performed after ablative surgery for head and neck squamous cell carcinoma: 86 pedicled pectoralis major island and 41 free flaps of different types. One hundred and four were evaluable for this retrospective study: 66 after definitive radiotherapy (6000-8000 cGy) and surgery for recurrent or persistent disease and 38 after elective surgery for Stage III and IV tumors without previous irradiation. Wound healing, hospital stay, survival rate and complications are compared between irradiated and nonirradiated areas. The indications, advantages and disadvantages of each type of flap are reviewed according to the main goals of our treatment: i.e. local disease control, restoration of function, cosmetic appearance and short hospital stay. PMID- 2599128 TI - [Histologic study of periapical granulomas]. AB - Sixty-three periapical granulomas were histologically examined. They were divided into four types: exudative, granulomatous, granulofibrous and fibrous types. The most frequent forms were the granulomatous types. The granulomatous type consisted of four zones: necrotic, exudative, granulomatous and fibrous. In the granulomatous zone lymphocytes, plasma cells, macrophages, Russel bodies, foam cells, neutrophil leukocytes were found. Mast cells were found in the fibrous zone among the collagen fibres. PMID- 2599129 TI - [The interaction of transcallosal and ascending excitation flows in the visual cortex of the cat]. AB - The conformity of interhemispheric interaction in visual cortex were studied by means of EPs recordings in 10 immobilized cats under conditions of different time combinations of transcallosal and monocular stimulation of contra- or ipsilateral eyes. Phasic changes of the depression effects under transcallosal conditioning of facilitating effects under conditions of the model interaction similar to natural transcallosal interrelations, occurred in photostimulation of contralateral eye. Whereas the ipsilateral eye stimulation only depressed the time interaction under these conditions. The findings are discussed in terms of morphological, neurophysiological and other research data on transcallosal interhemispheric relations in the cat visual cortex. The 15-25-ms interval between heteromodal stimuli under these research conditions seem to correspond to natural conditions of transcallosal interhemispheric relations which, in binocular vision, are dynamically and topographically organized processes of excitation and inhibition. PMID- 2599130 TI - [The perception of complex signals by cats under free behavioral conditions]. AB - Four adult cats were trained to discriminate between tones of rising and falling frequency or intensity. Food reward was used for conditioning. The difference limits for central frequency of 2.5 kHz were 150 Hz; 1.6 dB for FM and AM modulated signals, respectively. PMID- 2599131 TI - [The effect of stimulation of the hypothalamic "reward areas" on evoked potentials in the parafascicular complex of the thalamus]. PMID- 2599132 TI - [Neurophysiological analysis of the action of piracetam on the hippocampal neurons in rabbits]. AB - The unit activity in the hippocampus formation under the effect of pyracetam was found to depend on the latter dose in rabbits. The ligand-receptor interrelationship with pyracetam seems to exist at the level of the hippocampus formation. PMID- 2599133 TI - [The neuronal reactions of the area of the tractus solitarius nucleus in the cat to electrical stimulation of the gastric branch of the vagus nerve]. AB - Electrical stimulation of the vagus' gastric branch evoked three types of responses in the solitary tract nucleus of anesthetized cats: phasic discharges, tonic excitation and tonic inhibition. The majority of neurons with phasic and tonic inhibitory types of the responses were found in caudal part of the nucleus. The neurons whose spontaneous activity was increased during repetitive stimulation, were located in the rostral part of the nucleus. PMID- 2599134 TI - [The muscular activity of the forelimbs in the guinea pig with cerebellum removed undergoing vestibular stimulation]. AB - The influence of the cerebellum removal on the action of vestibular system on locomotor activity was not sufficient for the initiation of locomotor rhythmic activity and did not change its timing although vestibular effects on locomotor activity were preserved. The dynamics of vestibulo-spinal influences in experimental animals were the same as in animals with intact cerebellum. The intactness of cerebello-vestibular connexions seem not to be necessary for actualization of the vestibular system effects on locomotor activity. PMID- 2599136 TI - [The detoxifying function of the liver following its denervation in rats]. AB - The content of cytochrome P450 and b5 as well as basic microsomal enzymatic activity were studied in the liver of mixed male rats within 7 days of subdiaphragmatic vagotomy and/or large and small sympathetic nerves cutting. A decrease in the content of cytochromes and amidopyrine-N-demethylase, aniline hydroxylase and MADP-H-cytochrome-c-reductase activity was discovered both in the vagotomy and in the sympathectomy. A total denervation of the liver leads to a more significant suppression of enzymatic activity. A revealed acceleration of the blood flow and an insignificant decrease of the oxygen tension in the denervated liver tissue suggest that the above changes were due to switched off regulation of the nervous system rather than to the consequence of hypoxia. PMID- 2599135 TI - [The mechanism of an alteration in the erythrocyte electrophoretic mobility of heat-acclimated animals]. AB - Electrophoretic mobility of the heat-acclimated rat erythrocytes increased during a prolonged heat exposure and depended of plasma factors. PMID- 2599137 TI - [The effects of administering kynurenine into the dorsal hippocampus area in dogs]. PMID- 2599138 TI - [Scanning encephaloscopy]. PMID- 2599139 TI - [A miniature multichannel micromanipulator for the independent shifting of microelectrodes in a bundle]. PMID- 2599140 TI - [A method for studying neuronal thermosensitivity in co-incubated slices of different sections of the brain]. PMID- 2599141 TI - [An analysis of biopotentials in the neuromuscular junction using a computer]. PMID- 2599142 TI - Posterior composites: an update. PMID- 2599144 TI - Growing your numbers by developing people. PMID- 2599143 TI - Localized periodontal defect in a child. PMID- 2599145 TI - Smokeless tobacco use among Florida teenagers: prevalence, attitudes, and oral changes. PMID- 2599147 TI - CIT International Scientific Colloquium. 'Toxicology of pesticides--present and future--national and international views'. 29th November 1988, Paris, France. PMID- 2599146 TI - Halcion: an oral alternative to i.v. sedation. PMID- 2599148 TI - Toxicological and ecotoxicological evaluation of agropharmaceuticals with a view to their validation in France. PMID- 2599149 TI - Comparative study on the national legislations of the European Economic Community countries on phytosanitary substances with the European Council's Directives. PMID- 2599150 TI - Regulation of pesticides in the Federal Republic of Germany. PMID- 2599151 TI - Safe uses of pesticides within the WHO programme. PMID- 2599152 TI - Assessment of hazards to workers applying pesticides. AB - Exposure to pesticides as a result of their use in agriculture will vary according to the type of formulation, the method of application and the protective measures used. Quantitation of external exposure does not on its own predict the amount absorbed nor does it allow the toxic hazard to be assessed; information on skin penetration is also required. With the use of a suitable generic database for exposure, the assessment of many compounds would only require the measurement of skin penetration. With the knowledge of human dermal pharmacokinetics a field study can be performed which measures the absorbed dose directly and avoids the need for exposure measurement. PMID- 2599153 TI - Role of metabolism and pharmacokinetic data in the toxicological evaluation of pesticides. PMID- 2599154 TI - Relevance of kinetic and metabolic data to the interpretation of toxicological findings. AB - Metabolic and kinetic data on pesticides are now becoming an important part of the toxicological dossier required for product registration. In this paper the approach by one agrochemical company to generating such data is discussed. Metabolic data for the acaricide clofentezine are presented to illustrate why such data should be regarded as not only an important registration requirement, but also as integral to understanding the toxicological profile of pesticides. PMID- 2599156 TI - Residues--Good agricultural practice. PMID- 2599155 TI - Difference between species in response to a 3,5-dichloropyridyloxyphenoxy compound: induction of cytochrome P-450 and/or peroxisome proliferation. AB - In toxicological studies, the test compound FOE 3440 A, a [(3,5-dichloro-2 pyridyl)oxy]phenoxypropanoate with herbicidal properties, produced a severe increase in weight and an intensive induction of monoxygenases activity in the mouse, but not in the rat. Comparative subacute studies were performed with oral administration of 0, 5, 20 and, in some instances, 80 mg kg-1 body weight to mice, rats, hamsters, dogs and rhesus monkeys. Liver enzyme activities were measured. The evaluation of the enzyme activity results showed an unusually severe dose-related induction of the monooxygenases [7-ethoxycoumarin-O deethylase (EOD), 7-ethoxyresorufin-O-deethylase (EOR) and aldrin epoxidase (ALD)] in the mouse and a much weaker reaction in the other species tested. This exceptional position of the mouse was also demonstrated in vitro by a cytochrome P-450 interaction (inhibition of ALD). The primary metabolite of FOE 3440 A produced a distinct inhibition of the ALD in mice liver microsomes. There were no interactions for the other species. Tests for this cytochrome P-450 interaction using microsomes from three different human livers gave no indications of an inhibition in any case. The 'phenoxypropanoic acid' moiety of FOE 3440 A is structurally similar to the pharmaceutical clofibrate, a familiar model substance for peroxisome proliferation. In order to answer the question of whether peroxisome proliferation is the second mechanism for affecting liver, the carnitine acetyl transferase activity (CA-T), a marker enzyme for peroxisome proliferation, was determined in all liver samples from the comparative species studies. The most striking result of the measurement of CA-T activity was the very large increase in the male rat in the low dose group of 5 mg kg-1. Lesser increases in the CA-T activity were measured in the female rat, the mouse, and also in the 20 mg kg-1 group of the hamster. By comparison, the changes of the activity in dog and monkey were very small. Comparative studies in mouse and hamster using a model substance described in the literature (1,4-bis[2-(3,5 dichloropyridyloxy]-benzene (TCPOBOP] indicated that the '3,5-dichloropyridyloxy' moiety of FOE 3440 A is responsible for the induction of the monooxygenases in the mouse and the 'phenoxypropanoic acid' moiety for the peroxisome proliferation in rodents. PMID- 2599157 TI - New approaches in the toxicological evaluation of pesticides. PMID- 2599158 TI - WHO drinking water quality guidelines for selected herbicides. AB - Following the successful introduction of its Guidelines for Drinking-Water Quality in 1984, the WHO Regional Office for Europe was approached by the Government of Italy to develop, as a matter of urgency, recommendations for guidelines levels of certain herbicides found in drinking water supplies. Realizing the extent of the problem, the Regional Office for Europe organized two consultations to develop drinking water quality guidelines for the following 11 herbicides most commonly used in Italy: alachlor, metolachlor, pyridate, atrazine, molinate, simazine, bentazon, pendimethalin, trifluralin, MCPA and propanil. The presence of these and other herbicides in ground and surface water has been reported in several countries. Although the main purpose of these guidelines is to provide guidance to the Government of Italy in making risk management decisions, the information given was also intended to assist the other countries of the European Region in setting standards or in developing alternative control procedures where the implementation of standards is not feasible. The purpose of this paper is to review the process of health risk assessment used in the development of the WHO drinking water quality guidelines for selected herbicides. It will also reveal the major dilemmas and concerns expressed by the participating experts during the process of scientific deliberations, in the interests of understanding the complex issues involved in reaching the bare figures of the recommended guidelines. PMID- 2599159 TI - Evaluation and regulation of pesticides in drinking water: A Canadian approach. AB - Pesticides are registered in Canada under the authority of the Pest Control Products Act, administered by the Department of Agriculture. Pre-market registration requirements include submission of extensive toxicology data in order to allow evaluation of potential human hazards which may be associated with exposure to pesticides. Drinking water guidelines in Canada, although under provincial jurisdiction, are generally recommended by the federal government with collaboration of provincial authorities. In 1987, 42 pesticides were selected for development of guidelines for drinking water. When complete, the 42 pesticides will represent approximately 80% of all agricultural pesticides utilized in Canada, based on active ingredient weight sold. As do many other regulatory agencies, the Department of National Health and Welfare uses two different approaches to derive health-based guidelines or maximum acceptable concentrations of pesticides in drinking water. The threshold approach assumes that there is a dose below which no adverse effect will occur. This threshold level is closely related to the experimentally determined no observed adverse effect level and, when divided by an appropriate uncertainty or safety factor, forms the basis for the establishment of the maximum acceptable concentration. The second approach is the non-threshold or risk assessment approach and this assumes that these is some probability of harm at any level of exposure. This latter approach is generally utilized for chemicals believed to be capable of causing cancer and has not been used for any of the existing 29 pesticide drinking water guidelines developed in Canada. PMID- 2599161 TI - Is there a paradental in your future? PMID- 2599160 TI - Trends in dental assistant utilization: a comparative study. Part I. PMID- 2599162 TI - From four-handed dentistry to prophylaxis ... who's going to do the work? PMID- 2599163 TI - The use of gloves in dentistry. PMID- 2599164 TI - AIDS is spreading. PMID- 2599165 TI - Mouth disorders occur in AIDS-infected patients. PMID- 2599166 TI - Helping patients quit smoking: the role of the dental assistant. PMID- 2599167 TI - Trends in dental assistant utilization: a comparative study. Part II. PMID- 2599169 TI - Gum disease affects youth in varying degrees. PMID- 2599168 TI - Following the commandments of sound collections. PMID- 2599170 TI - Basic handwashing: a refresher course. PMID- 2599171 TI - Improving your practice's image. PMID- 2599172 TI - Glove quality is best safeguard against infection. PMID- 2599173 TI - Should selling products be a part of your practice? PMID- 2599174 TI - Video computer imaging enhances esthetic outcomes. PMID- 2599175 TI - Selling a dental practice--what to consider. PMID- 2599176 TI - A crisis in dentistry: practice expectations unmet. PMID- 2599177 TI - Jane-of-all-trades. PMID- 2599178 TI - The tetracyclines. PMID- 2599179 TI - History repeats itself ... again. PMID- 2599180 TI - Dental fees: national and regional survey. PMID- 2599181 TI - How lawyers pick the dentists they'll sue. PMID- 2599182 TI - Presenting excellence: polish your communication skills. An interview with Dr. Gordon Christensen. Interview by Mark Saxen. PMID- 2599183 TI - Good hygienists are hard to find: are they a dying breed? PMID- 2599184 TI - Antifungal agents. PMID- 2599185 TI - Ask and you shall receive. PMID- 2599186 TI - The future of dentistry: a call for leadership. PMID- 2599187 TI - Understanding liability insurance: the "tail" termination. PMID- 2599188 TI - Passing the baton: two generations talk about the profession. Interview by Eric Shroder. PMID- 2599189 TI - Periodontal considerations in cosmetic dentistry. PMID- 2599190 TI - Overusing strengths. PMID- 2599192 TI - US funds for AIDS grow to $1.3 billion. PMID- 2599193 TI - Are you listless? PMID- 2599191 TI - Miscellaneous antibiotics of interest to dentists. PMID- 2599194 TI - What lasers can do for dentistry and you. PMID- 2599195 TI - Keep it simple: practicing with one employee. PMID- 2599196 TI - How to handle your new patients. PMID- 2599197 TI - 18 ways to start out right in private practice. PMID- 2599198 TI - Don't legislate glove use. PMID- 2599199 TI - Effective delegation: make your staff more productive. PMID- 2599200 TI - Space-sharing: the consultant's way or my way? PMID- 2599201 TI - Marketing the excellence-oriented practice--an interview with Stuart L. Isler, DMD. Interview by Mark Saxen. PMID- 2599202 TI - Advanced education for front desk personnel can pay big dividends. PMID- 2599203 TI - Fitting TMJ patients into your practice: is it right for you? PMID- 2599204 TI - AIDS disclosure legislation amended to protect providers. PMID- 2599205 TI - The relationship between periodontal status and reported oral hygiene activity in a population of Asian females. PMID- 2599207 TI - In the face of adversity. PMID- 2599206 TI - The role of the dental hygienist in recognition and management of juvenile periodontitis. PMID- 2599208 TI - A closer look at office costs. PMID- 2599209 TI - Talk to patients about infection control. PMID- 2599210 TI - Selecting your computer system. PMID- 2599211 TI - Male and female dentists talk about stress and coping. PMID- 2599212 TI - Office humor keeps patients coming back. PMID- 2599213 TI - A dentist's guide to life insurance. PMID- 2599214 TI - Marketing your practice with pegging. PMID- 2599215 TI - A primer for newsletter publishing. PMID- 2599216 TI - Let staff know how they're doing. PMID- 2599217 TI - Building relationships. PMID- 2599218 TI - Transmit peak performance. PMID- 2599219 TI - Dentinal hypersensitivity and practice-building. PMID- 2599221 TI - Ease the pain of staff dismissals. PMID- 2599220 TI - Overpowering OSHA. PMID- 2599222 TI - Consider TMJ. PMID- 2599223 TI - Funding for AIDS research, prevention and education. PMID- 2599224 TI - Influencing patients to accept treatment. PMID- 2599225 TI - Collecting overdue accounts by phone. PMID- 2599226 TI - Collector's creed. PMID- 2599227 TI - Who controls your controls? PMID- 2599228 TI - Getting back to basics with computers. PMID- 2599229 TI - Natural-looking dentures. PMID- 2599230 TI - The visual building technique. PMID- 2599231 TI - Image layers in the Zonarc. AB - The Zonarc (Palomex Oy, Helsinki, Finland) uses the principles of rotational panoramic radiography to image various structures of the head and neck. System parameters obtained from the manufacturer have been used to derive data on the imaging characteristics of the Zonarc when using each of the following programmes: MT, DENT, TMJ, EAR, CV and LAT. The beam path along with the shape, position and relative thickness of the layer has been calculated for each programme, together with the resolution and magnification associated with the different layers. PMID- 2599232 TI - Effect of developer temperature changes on the sensitometric properties of direct exposure and screen-film imaging systems. AB - A heat exchanger was developed and incorporated into the recirculation system of a dental processor to maintain strict temperature control. Without the heat exchanger, developer temperature rose steadily over 8 h to a maximum of 35.7 degrees C: with the heat exchanger it was maintained, regardless of ambient conditions, at the desired temperature with virtually no fluctuation. Sensitometric properties of base and fog, speed, and average gradient were measured for D and E speed films and Lanex Regular/T-Mat G and Lanex Fast/T-Mat Hscreen-film systems at developer temperatures of 21.1, 23.8, 26.7, 29.4 and 32.2 degrees C. Small changes in these properties were found for D and E speed films: on the other hand, Lanex Regular/T-Mat G showed a 65% increase in base and fog and Lanex Fast/T-Mat H a 43% increase in average gradient over the temperature range studied. Although these changes may not be clinically significant for intra oral and dental radiography, the variations in image quality may compromise controlled imaging experiments and clinically compromise radiographic quality when using screen-film systems. PMID- 2599233 TI - Information yield: a comparison of Kodak T-Mat G, Ortho L and RP X-Omat films. AB - The information yield from two rare-earth screen-film combinations, Lanex Regular/T-Mat G (TMG) and Lanex regular/Ortho L (OL) has been compared with that from a conventional calcium-tungstate combination, X-Omatic regular/RP X-Omat (XRP), by means of perceptibility curves generated from an aluminum test object. The TMG and OL systems were faster than the XRP and the OL had the widest latitude. The maximum number of details perceived was similar for all three systems. The results support the suggestion that the TMG and OL systems permit more information to be perceived than XRP and that the newer imaging systems do not lose information despite their increased speed. PMID- 2599234 TI - The optimum level of radiopacity in posterior composite resins. AB - Radiopacity is an indispensable property of composite resins for clinical diagnosis. The level of radiopacity that is most compatible with the radiographic diagnosis of recurrent caries was studied in a two-part experiment. In the first part, 16 composities were evaluated and divided into four groups based on their levels of radiopacity compared with an aluminum stepwedge. In the second part, caries was simulated by grooves of increasing depth in aluminum blocks of a thickness equivalent in radiopacity to enamel and the detectability assessed beneath differing thicknesses of three representative composite resins, P-30, Brilliant Lux and Occlusin. The relative radiographic density was measured and P 30 found to have the greater contrast. It is proposed that composite materials with a radiopacity similar to enamel are best for the detection of recurrent caries. PMID- 2599235 TI - An anatomical radiolucency of the cervical spine. AB - A radiolucency in the cervical spine consistently seen on panoramic dental radiographs has been investigated. It was found to arise from the axis and be caused by a combination of its unique morphology and the oblique angle of incidence of the X-ray beam in the first part of its rotation. PMID- 2599236 TI - Radiological studies of experimentally induced sialoadenitis of the mouse parotid gland: quantitative microsialography and histology. AB - Sialoadenitis was induced experimentally in mouse parotid glands and the changes in gland morphology analysed over a period of 60 days by means of quantitative microsialography and histology. The microsialogram was digitized as an intensity histogram and the glands evaluated for seven histomorphometric parameters involving both the acini and duct systems. Differences in the intensity-histogram between experimental and control glands were shown to represent changes in duct architecture in the presence of inflammation, while differences in the relative frequency of pixels between low- and high-intensity areas were found to be due to a decrease in intralobular duct size, and acinar size and number in the former compared with an increase in the major duct components in the latter. PMID- 2599237 TI - Age-dependent decrease in the computed tomographic numbers of parotid and submandibular salivary glands. AB - The computed tomographic (CT) numbers of 182 normal parotid glands were measured in patients ranging in age from 1 to 81 years, and of 172 normal submandibular glands with an age range of 1-85 years. The mean CT number (+/- s.d.) of the parotid and the submandibular glands was -10 +/- 24 Hounsfield units (HU) and 41 +/- is HU respectively. Sex and intra-individual differences in the CT numbers were small, but significant linear decreases were found with age in both glands. The mean annual decrease was 0.5 HU. PMID- 2599238 TI - The importance of radiography in assessing the behaviour of an aggressive giant cell lesion of the jaws. AB - A case of an aggressive giant cell lesion is reported. In view of the problems associated with histopathological diagnosis, long-term clinical and radiographic follow-up of any giant cell lesion is mandatory. PMID- 2599239 TI - Primary intra-osseous carcinoma of the maxilla. AB - An unusual case of maxillary carcinoma, diagnosed as a primary intra-osseous carcinoma, is reported. This was differentiated from primary carcinoma of the maxillary sinus on the basis of the radiographic findings and the patient's dental history. PMID- 2599240 TI - Scanning electron microscopy of submandibular sialoliths: a preliminary report. AB - This report compares the scanning electron microscopic appearances of the structures in two sialoliths, one surgically removed, the other naturally exfoliated. The first exhibited the typical structure of a lamellated outer layer with an amorphous core. The core contained a large number of structures resembling calcified filamentous organisms. The second consisted of a similar outer lamella but the core contained crystal-lined spaces, amorphous matrix and an heterogeneous array of crystal shapes: there were no structures resembling organisms. PMID- 2599241 TI - Periodontal disease and treatment in the elderly: 1. PMID- 2599242 TI - Restoration of the broken down primary molar: 1. Pulpectomy technique. PMID- 2599243 TI - Prevalence and nature of HIV. PMID- 2599244 TI - Pre-prosthetic preparation of the mouth. PMID- 2599245 TI - Fluoridated dentifrices and early enamel lesion remineralization. PMID- 2599246 TI - Periodontal disease and treatment in the elderly: 2. PMID- 2599247 TI - Cross infection control in dentistry: 1. General concepts and surgery attire. PMID- 2599248 TI - Supernumerary teeth. PMID- 2599249 TI - Restoration of the broken down primary molar: 2. Stainless steel crowns. PMID- 2599250 TI - Effect of folate supplement on pregnant women with beta-thalassaemia minor. AB - The effect of folate supplement on the haemoglobin concentration and outcome of pregnancy was studied in a group of Chinese women with uncomplicated beta thalassaemia minor who delivered in our hospital between 1984-1987. The patients who received 5 mg folate daily showed a significant increase in the predelivery haemoglobin concentration, which was significantly higher than that in patients who received 0.25 mg daily. When the effect of parity was analysed we found that: multiparas were significantly older, had lower haemoglobin before delivery, and more of them required transfusion. Folate 5 mg daily significantly increased the predelivery haemoglobin concentration in both nulliparas and multiparas. It is concluded that folate 5 mg daily improves the haemoglobin concentration in pregnant women with beta-thalassaemia minor and that this should be prescribed. PMID- 2599251 TI - Antenatal complications and perinatal outcome in patients with nausea and vomiting-complicated pregnancy. AB - The incidence of nausea and vomiting-complicated pregnancy was determined in a district hospital in Hong Kong. Nausea was present in 11.4% and vomiting in 63.5% of pregnant women. Patients with vomiting complicating early pregnancy have a statistically significant higher incidence of antepartum haemorrhage of indeterminate origin. The incidences of medical diseases complicating pregnancy, other major antenatal complications, and the neonatal outcome were not different between vomiting and non-vomiting patients. PMID- 2599252 TI - The natural course of habitual abortion. AB - In recurrent spontaneous abortion an immunological fetal-maternal imbalance has been postulated and successes of immunotherapy have been described. A prospective study on the reproductive performance of untreated women with three abortions of unknown etiology has not been performed. The benefit of therapy can only be estimated if the natural course of the disease is known. The aim of this study was to investigate prospectively the abortion rate in a well-defined group of women with a history of habitual abortion of unknown etiology and to test the hypothesis that immunologic factors are involved. Fourty-four couples were taken into study. The overall pregnancy rate in the first subsequent pregnancy was 62%. Neither significant increased sharing of Human Leucocyte Antigens (HLA) nor an aberrant mixed lymphocyte reactivity in this group was found when compared to control random matings. The presence or absence of antipaternal antibodies did not correlate with the outcome of the subsequent pregnancy. It is concluded that the prognosis of untreated patients with habitual abortion is favourable and that no aberrant immunologic reactivity could be demonstrated by means of up-to-date diagnostic procedures. PMID- 2599253 TI - Detection of sperm-bound antibodies in the male partners of infertile couples using the immunobead test. AB - The aim of this investigation was to determine the incidence of sperm-bound antibodies in the male partners of an unselected infertile population using an immunologically specific test (IBT). With this method 34 out of 450 infertile men (7.55%) were positive for one or more of the immunoglobulins IgA, IgG and IgM. For IgG and IgA, the majority of antibody binding was located on the entire sperm with a minor amount bound to the head or tail. For the IgM, the majority of the binding was detected to the tail tip, and tail binding was observed only in a minority of cases. PMID- 2599254 TI - Test of immunopotentialization in colposcopy--a clinical evaluation. AB - 52 infertile women (age range 19-35 years) treated by Gynatren immunopotentialization (three vaccinations every second week) were divided into two groups according to appearance of cervical intraepithelial neoplasia (CIN). 30 women had CIN cytologically diagnosed and proved by colposcopy (group II). Colposcopic examinations were performed on the first day of therapy (first vaccination), after two weeks (second vaccination) and after four weeks (the day of the third injection). Four weeks of the therapy resulted in normalization of cervical milieu (e.g., complete regression of infection in 68.2% of I group and 56% of II group) as well as in disappearance of CIN in 66% of cases and in remaining ones there was a 7-times decrease of CIN II. It was colposcopically stated that the process of statistical significant regression of inflammation as well as normalization of cervical pathology is less apparent in women with CIN. These findings confirmed our previous cytological observations. PMID- 2599255 TI - Urethral pressure variations diagnosed by multiple urethral pressure transducers. A common phenomenon in women suffering from urinary incontinence. AB - The prevalence of urethral pressure variations (variation of urethral pressure greater than 15 cm H2O) was investigated, with the use of a data-based multitransducer catheter, in female patients suffering from urinary incontinence. Urethral pressure variations were diagnosed in 45 (63%) of 71 patients. This prevalence was greater than in previous studies, possibly for methodological reasons; the urethral pressure was simultaneously measured by five urethral microtransducers, thereby registering all variations in maximal urethral pressure. The present method also showed that urethral pressure variations were simultaneously present in different urethral sites, but that the amplitude of variation differed between the different points of registration. In most cases, urethral pressure variations were already apparent at the start of urethrocystometry. Voluntary holding, in an effort to inhibit the desire to void, can cause these variations in urethral pressure. Hence urethral pressure variations may be a normal physiological phenomenon. PMID- 2599256 TI - Repeated tubal pregnancies in women with a single tube followed by uncomplicated pregnancies. Two women experiencing seven ectopic gestations. AB - Two patients each having one salpinx removed because of ectopic pregnancy, both had two ectopic pregnancies in the remaining tube. Conservation of the tubes was later followed by normal intra-uterine pregnancies and deliveries. PMID- 2599257 TI - Air embolism following intra-uterine hypertonic saline instillation: treatment in a high-pressure chamber; a case report. AB - Air embolism was encountered in a patient following induced abortion by means of intra-amniotic hypertonic saline instillation. The only symptom present was isolated cortical blindness. The patient was treated in a high-pressure chamber and a nearly complete recovery was achieved. PMID- 2599258 TI - Chronic tuboovarian abscess due to Staphylococcus aureus: a case report and literature review. AB - A 40-year-old woman presented with a right adnexal mass. Laparotomy revealed a large tuboovarian abscess due to Staphylococcus aureus. The only significant past medical history was a Cesarean section and bilateral tubal ligation 10 years prior to admission. The tuboovarian abscess, due to this unusual organism, may have developed insidiously over a 10 year period. The patient recovered completely after excision of the abscess and antibiotic treatment. PMID- 2599259 TI - QRS changes in direct fetal electrocardiogram during uterine overstimulation; report of four cases. AB - Four cases are presented in which increased QRS complex voltages or deviation of the mean electrical axis were observed in the fetus by direct fetal electrocardiogram (ECG) during delivery under anaesthesia. There was transformation of the initial QRS aspect before delivery. These changes were only observed when large doses of oxytocin (20 IU in 500 ml) were used after Pentothal administration in deliveries in which other fetal ECG alterations (bradycardia, ST changes, T inversion) and/or low pH values had been observed. In case 1 there were ST level changes, inversion of the T wave and transformation of the QRS complex from RS to Rs. Case 2 showed a change from RS to QR type complex associated with repolarization defects. In cases 3 and 4, ST level changes, inversion and increased QRS complex voltages were observed. We checked that the modifications observed were not due to changes in position of the fetus during recording. It is thought that the acute redistribution of the fetal blood volume due to oxytocin overstimulation in fetal hearts with hypoxic signs may lead to compensatory mechanisms such as tachycardia, increased contractile activity (higher QRS) and functional predominance of one side of the fetal heart (deviation of the electrical axis) subjected to sudden load. PMID- 2599260 TI - Characterization and differential expression of an endothelial cell-specific surface antigen in continuous and sinusoidal endothelial, in skin vascular lesions and in vitro. AB - Continuous and sinusoidal endothelial cells display marked morphological and functional heterogeneity as to their plasmalemmal vesicle content, to the kind of intercellular junctional complexes, to the existence and kind of fenestrae and gaps, to the existence and character of their basement membrane, to their ability for phagocytosis and to other functional parameters. Monoclonal antibody 1F10, raised against human umbilical vein endothelial cells (HUVE cells), reflects these differences in recognizing--without any nonendothelial side reactions--an endothelial cell surface antigen, abundantly expressed in continuous endothelia, low and inconsistently expressed in liver sinusoidal and dermal lymphatic endothelia and absent from splenic sinusoidal endothelial cells. In differentiated skin vascular tumors, 1F10 antigen is expressed in normal amounts while it is only low and inconsistently expressed in the dedifferentiated endothelial cells of Kaposi's sarcoma and hemangiosarcoma. HUVE cells in culture, in contrast to their in situ ancestors, express variable amounts of 1F10 antigen. When endothelial cell-conditioned medium (ECC medium) is supplied to HUVE cells in culture, no 1F10 antigen is expressed, while supplementation with fresh serum containing medium (FSC medium) or cytokines, such as bFGF, suffices to maintain 1F10 expression in 10-70% of the cells. From this we conclude that developmental regulation, environmental influences and cytokine supply contribute to the differentiation and maintenance of the 1F10+ and 1F10-endothelial cell phenotypes, both in vivo and in vitro. PMID- 2599261 TI - Putative mesothelial cell growth-promoting activity of a cytoplasmic protein expressed by the mesothelial cell. A preliminary report. AB - Mesothelioma cells produce a cytoplasmic protein unique to primary tumours of the mesothelium which induces the in vitro proliferation of human mesothelial cells in a dose-dependent fashion. When a polyclonal antibody to this protein was added to cultures of human mesothelioma cells, inhibition of their growth occurred. These results provide evidence for a growth-factor-like role of this mesothelial protein that may act through an autocrine mechanism. PMID- 2599262 TI - Effects of TGF-beta on retinal pigmented epithelium in vitro. AB - Embryonic chick retinal pigmented epithelium (RPE) has been grown on glass derivatized with covalently bound proteins of basement membrane and treated with transforming growth factor-beta (TGF-beta). In the present paper we show that over the concentration range tested (0.1-10 ng/ml) TGF-beta has no effect on RPE cell proliferation either in the presence or the absence of serum, cell motility and the organization of cytoskeleton-extracellular matrix linkage complexes with respect to their structure and presence of actin, vinculin, talin, integrin and fibronectin. The protein profiles of total cell/ECM extracts of cells grown in the presence or the absence of TGF-beta are similar although some stimulation of protein synthesis and of production of fibronectin-containing extracellular matrix has been detected. PMID- 2599263 TI - In vitro interaction of heterologous platelets with isolated neoplastic cells from a murine mammary gland tumor. AB - The purpose of the present work was to study the in vitro effects of challenging human whole-blood and platelet-rich plasma (PRP) with neoplastic cells (NC) isolated from a murine mammary gland adenocarcinoma. Viable, but not formalinized, isolated tumoral cells induced platelet aggregation in citrated whole blood. NC did not induce aggregation of PRP samples whereas the NC added to PRP induced aggregation in 33% of volunteers if samples were previously stimulated with a subaggregatory strength of collagen. The results suggest a role for other blood cells since the proaggregatory effect was less evident on PRP. Adenocarcinoma M3 seems to be a suitable model to study in vitro platelet-cell tumor interactions. PMID- 2599264 TI - Brain and behaviour. PMID- 2599265 TI - Asperger's syndrome and autism: comparison of early history and outcome. AB - The authors compared children with Asperger syndrome (AS) with high-functioning autistic children and psychiatric outpatient controls on measures of early history and outcome. In terms of their early history, the autistic probands showed more social impairment, a higher frequency of echolalia and pronoun reversal, and a more restricted range of activities than the AS group. Cluster analysis suggested refinements to the diagnostic criteria, which resulted in larger differences between the groups on these early history measures. In terms of their outcome, the autistic probands spent more time in special education classes but developed fewer accessory psychiatric symptoms than the AS children. It was clear, however, that there were no substantive, qualitative differences between the AS and autistic groups, indicating that AS should be considered a mild form of high-functioning autism. The inclusion of AS among the autistic spectrum of disorders has implications both for aetiological studies and for prevalence estimates of the pervasive developmental disorders. PMID- 2599266 TI - Electrophysiological effects of fenfluramine or combined vitamin B6 and magnesium on children with autistic behaviour. AB - The authors compared the effects of fenfluramine or combined vitamin B6 and magnesium treatment on the evoked potential conditioning of 12 children whose autistic behaviour had improved clinically following treatment. The children who were clinically sensitive to combined vitamin B6 and magnesium developed a conditioning phenomenon and the fenfluramine-sensitive children showed an enhancement of the Cz evoked response amplitude. Results are discussed with reference to behaviour modifications observed during treatment. PMID- 2599267 TI - Developmental history and neurological findings in enuretic children. AB - One hundred and fifty-six enuretic and 170 control children were examined to identify neurological abnormalities and group dissimilarities. Developmental and perinatal histories were checked and the Test of Motor Impairment administered. The enuretic group had greater fine and gross motor clumsiness and perceptual dysfunction than the control group. Children who had been small for gestational age, who had suffered asphyxia or shown neurological symptoms during the neonatal period had a higher risk of developing daytime or day- and night-time enuresis at a later stage. With the exception of toxaemia, perinatal risk signs were not seen in the children with night-time enuresis only, but they had the slowest growth rate. It is suggested that there are at least two different groups of enuretic children: those with daytime or day- and night-time enuresis, whose condition is associated with neurological damage; and those with an obvious delay in maturation of central nervous bladder control, who have night-time enuresis only. PMID- 2599268 TI - Chronic physical illness in childhood: psychological and social effects in adolescence and adult life. AB - A national birth cohort followed for 36 years was used to compare the life chances of individuals with chronic physical illness in childhood with those of controls. The majority of those who had been chronically physically ill in childhood were found to differ very little in social and psychological circumstances by 36 years of age, but earlier in adult life there had been signs of difficulties. However, there was a disturbing tendency for those from lower social-group families to be in significantly worse social and psychological circumstances, and by 36 years they showed signs of relatively poor life chances and of basic social support, including the death of both parents. PMID- 2599269 TI - Relationship between neurodevelopmental status of very preterm infants at one and four years. AB - The neurodevelopmental status of 171 very preterm infants was assessed at one and four years of age. At one year 17 had major impairments and 14 had minor ones. At four years the numbers had increased to 25 with major and 25 with minor impairments. Infants with no impairments at one year had a 4 per cent probability of a major impairment at four years, whereas infants with a major impairment had a 94 per cent probability. Infants who later proved to have major neuromotor impairments had been accurately identified at one year, as had infants with sensorineural hearing-loss. Infants with minor impairments of tone and reflexes at one year did not develop cerebral movement disorder, but as a group their scores on tests of cognitive functioning were low. An additional group of infants with cognitive impairments was identified who were unimpaired at one year. The emergence of cognitive deficits largely accounted for the increase in impairments between one and four years. PMID- 2599270 TI - Early prognosis for ambulation of neonatal intensive care survivors with cerebral palsy. AB - The ambulatory status of 74 neonatal intensive care unit survivors with cerebral palsy, excluding those with central nervous system malformations and syndromes, was assessed at eight years of age. Detailed examinations were completed at two and eight years of age; of the 47 who were sitting by two years, 46 became ambulatory, and a total of 47 of the 74 children became ambulatory. The clinical type of cerebral palsy at two years of age related significantly to eight-year ambulation. However, between two and eight years the diagnosis was changed for 18 children. At two years of age the tonic labyrinthine, asymmetrical and symmetrical tonic neck and Moro reflexes related significantly to ambulation; in five of 27 children not walking, these reflexes were absent by two years of age. Foot placement and/or parachute reactions at two years were found in more than one-third of children not walking. Multivariate analysis determined that age at sitting explained 91 per cent of the variance in ambulation. No other variables, combined with sitting, increased this prediction. PMID- 2599271 TI - Visual information processing in infancy. AB - The author examined the construct validity of visual information processing in infancy (preference for novel visual targets) as a predictor of later neurological outcome. 104 infants with definite (N = 25), questionable (N = 27) or no evidence of neurological dysfunction (N = 52) were tested at three to seven months (corrected age). The mean novelty preference scores differed significantly between the three groups. These differences were not related to demographic data and still existed when the data were corrected for preterm birth and birthweight. These results support the hypothesis that visual information processing at three to seven months (corrected age) is a reflection of neurological intactness and may be useful in the clinical assessment of cortical function in infants. PMID- 2599272 TI - Reversible neuromuscular syndrome in malnourished children. AB - Six young children are reported who were malnourished, with hypotonia, weakness and absent stretch reflexes, both proximally and distally, but with normal sensory examinations. Motor and sensory nerve conduction velocities also were normal. Five had mildly abnormal electromyograms, with scattered fibrillations, positive sharp waves and increased insertional activity, both proximally and distally. After adequate nutrition in hospital, all the children's reflexes returned and strength improved. Weight for height was an important indicator: it was decreased when the muscle stretch reflexes were absent and increased when they returned. The neurological and electrodiagnostic findings imply that this is a reversible lower motor-neuron or muscle disorder. PMID- 2599273 TI - Connatal Pelizaeus-Merzbacher disease. AB - Type II connatal Pelizaeus-Merzbacher disease is a degenerative disease of the developing nervous system. Confirmation of diagnosis is only by histopathological examination at present. The authors describe an infant with several clinical features which are apparently unique to this disease. These features may allow a presumptive clinical diagnosis to be made in other cases, thereby allowing valuable genetic counselling to be given before the death of the affected infant enables confirmation by autopsy. PMID- 2599274 TI - Rigid spine syndrome and progressive external ophthalmoplegia in a 15-year-old girl. AB - A 15-year-old girl presented with rigid spine syndrome (RSS) associated with a myopathy of benign course, marked proliferation of perimysial and endomysial connective tissue, severe scoliosis, and progressive paralysis of upward and lateral gaze. This is the first report of RSS and progressive ophthalmoplegia in the same patient. PMID- 2599275 TI - Preterm birth: to correct or not to correct. PMID- 2599276 TI - Relevance of EEG to prognosis in hemimegalencephaly. PMID- 2599277 TI - Is popliteal angle measurement useful in early identification of cerebral palsy. PMID- 2599278 TI - The effect of opiates on the intestinal immune response to cholera toxin in mice. AB - We studied the effect of opiates on the intestinal immunoglobulin A response in mice. C57BL mice were orally immunized by two doses of 10 micrograms of cholera toxin, 2 weeks apart. Experimental groups received subcutaneous injections of morphine, either 10 or 20 mg/kg/day, in two divided doses. Morphine was given for 4 days, starting 1 day prior to each cholera toxin dose. Intestinal secretions were collected by lavage 1 week after the last cholera toxin dose, and assayed for specific anticholera toxin antibody and total immunoglobulin A. Results were expressed as units of anticholera toxin per nanogram immunoglobulin A. It was found that morphine, 20 mg/kg/day, reduced the response from 30.9 +/- 3.11 to 9.78 +2- 1.42 units/ng (M +/- SEM; p less than 0.0001). 10 mg/kg/day of morphine slightly reduced the immune response to 21.38 +/- 3.51 units/ng (M +/- SEM), but failed to achieve statistical significance. Naloxone administration prior to morphine injections abolished the inhibitory effects of morphine. Morphine administration had no effect on the response to a booster dose of cholera toxin 3 months after the initial cholera toxin immunization and morphine administration. It is concluded that morphine has a significant inhibitory effect on the intestinal immune response, but does not effect long-term mucosal immunological memory. The effect is probably mediated by a specific opiate receptor, as it is blocked by naloxone. This effect may have clinical implications. PMID- 2599279 TI - Etiology and incidence of acute pancreatitis: a 20-year study in a single institution. AB - Reports from various countries raise the question of changes in the incidence and etiology of acute pancreatitis. This study covers patients admitted with acute pancreatitis to a single university department of medicine between 1965 and 1970 and between 1980 and 1985. The absolute number of patients admitted with acute pancreatitis doubled, whereas the percentage of pancreatitic patients in the total population of admitted patients decreased by 38%. No firm conclusion can be made about an increasing incidence of acute pancreatitis from 1970 to 1985. However, the dominating etiological factor was no longer biliary tract disease but significantly shifted to alcoholism, whereas changes in the severity of the disease were not significant. There was a downward trend in mortality with mortality rates of 13 and 8.6% for the first and second period, respectively; however, because of the small number of patients this change did not reach the level of significance. PMID- 2599280 TI - Incorporation of N-acetyl-[14C]D-glucosamine and [3H]L-leucine by isolated pig gastric mucosal cells. AB - Glycoprotein and protein production of isolated pig gastric mucosal cells were determined by the incorporation of N-acetyl-[14C]D-glucosamine ([14C]GlcNAc) and [3H]L-leucine ([3H]Leu) into acid-insoluble macromolecules (AIM). In four cell fractions (F1-F4), obtained by counterflow centrifugation, specific [14C]GlcNAc incorporation was greatest in the mucous cell-enriched F2. Tracer incorporation by F2 cells, proceeded linearly up to 20 h, was inhibited by cycloheximide or incubation at 0 degree C, and enhanced by PGE2 1 mumol/l. Gel chromatography of released AIM revealed that PGE2-stimulated [14C]GlcNAc incorporation was predominantly directed into high molecular weight (2 X 10(6) daltons) glycoproteins, whereas [3H]Leu incorporation was mainly related to proteins of albumin-like molecular weight. We conclude that incorporation of [14C]GlcNAc by enriched pig gastric mucous cells (F2), further analyzed by gel chromatography, is a suitable probe to study the production of high molecular weight gastric mucous glycoproteins in vitro. PMID- 2599281 TI - Experimental pancreatic cancer in the Syrian hamster: effect of cholecystectomy. AB - Because cholecystectomy stimulates hypertrophy and hyperplasia in the hamster pancreas, its effect on experimental pancreatic carcinogenesis was studied in this animal model. Forty female Syrian hamsters underwent cholecystectomy, while 40 others underwent sham operations. Two weeks later, 30 hamsters undergoing cholecystectomy and 30 hamsters undergoing sham operations received 4 weekly subcutaneous injections of N-nitroso-bis (2-oxopropyl) amine (BOP) (10 mg/kg). Remaining hamsters (n = 20) received equal volumes of 0.9% saline solution. A further 10 hamsters (controls) underwent no surgery and received no injections. Thirty weeks after the first BOP or saline injection the pancreas of hamsters that had undergone cholecystectomy was only 3% heavier than that of sham-operated animals, and there was no difference in the incidence of pancreatic cancer between BOP-treated hamsters that had undergone cholecystectomy and those that had undergone sham operations. In this study, cholecystectomy had no influence on BOP-induced pancreatic carcinogenesis in the Syrian hamster. PMID- 2599282 TI - Acute hemorrhagic pancreatitis in mice: improved survival after indomethacin administration. AB - This study was designed to test whether indomethacin given in drinking water attenuates the severity of the acute hemorrhagic pancreatitis induced in mice fed a choline-deficient ethionine diet (CDE), and improves their survival. Three doses of indomethacin were tested, 20, 10 and 5 mg of indomethacin/l of drinking water, and their effects on the histopathology of the pancreas and liver, serum amylase activity levels, and mortality were determined. Even though 20 and 10 mg/l suppressed pancreatic injury, and the accompanying shock-like state, the mice died due to indomethacin hepatotoxicity. Hepatotoxicity was minimal at a dose of 5 mg/l, which resulted in preservation of significant amounts of normal pancreatic parenchyma, subsequent regeneration of acinar cells, and an increased survival of the mice. The results suggest that prostaglandins may play an important role in the pathogenesis of acute hemorrhagic pancreatitis, and that indomethacin attenuates the severity of the induced disease. PMID- 2599283 TI - Quantitative estimation of the collagen content in normal and pathologic pancreas tissue. AB - The aims of the study were to measure the collagen content in pancreas using a colorimetric method and to compare the amount of collagen in normal pancreas (11 cases), diffuse fibrosing pancreatitis (17 cases), and chronic calcifying pancreatitis (11 cases). The procedure of fibrosis measurement was based on the selective capacity of two dyes, Sirius red and fast green, to set on collagen and noncollagenous proteins, respectively. After staining of sections, colors were eluted from the sections and the specific absorbance of each eluted dye was read on a spectrophotometer. The collagen content in normal pancreata was 26.5 +/- 7.2 micrograms collagen/mg protein. The amount of collagen increased with the age of patients: the mean value of the patients under the age of 50 was 18.2 +/- 4 micrograms collagen/mg protein whereas the mean value in older patients was 31.9 +/- 8 micrograms collagen/mg protein (p less than 0.01). The value of collagen in pancreas with a diffuse fibrosing pancreatitis was 44.7 +/- 7.5 micrograms collagen/mg protein. This value was significantly different from the collagen content in normal pancreas (p less than 0.001) and in pancreas with a chronic calcifying pancreatitis (77.9 +/- 8 micrograms collagen/mg protein, p less than 0.001). This method permits discrimination between different chronic diseases that can also be differentiated on a histopathologic basis. PMID- 2599284 TI - [Clinical and hemodynamic effects of medium-term ketanserin treatment in 2 compared groups of obese and non-obese hypertensive patients]. AB - We evaluated systemic and central hemodynamics in 10 lean hypertensives and in 10 obese hypertensives (WHO stage I-II) after 8 weeks treatment regimen with a serotoninergic antagonist such as ketanserin. At the beginning and at the end of the study, body weight, BMI, blood pressure and heart rate were measured and a first pass radionuclide angiocardiography was performed to determine cardiac output, cardiac index and ejection fraction of left ventricle. Total peripheral resistances were also calculated. In both hypertensive groups ketanserin significantly reduced diastolic (p less than 0.05) and mean (p less than 0.005) blood pressure. No significant change in systolic blood pressure, cardiac output, cardiac index and ejection fraction of left ventricle has been observed in lean and obese hypertensives. Total peripheral resistance values significantly (p less than 0.05) decreased in lean hypertensives; in obese hypertensives total peripheral resistance moderately reduced. Our results indicated that monotherapy with ketanserin is effective in treating mild to moderate hypertension both in lean and in obese hypertensives and did not interfere with left ventricular performance. At last the effectiveness of ketanserin treatment appears moderately higher in lean than in obese hypertensives. PMID- 2599285 TI - [Metoxibutropate]. PMID- 2599286 TI - [Concerning sexually transmitted diseases: mucocutaneous manifestations of HIV infection]. PMID- 2599287 TI - [Changes in blood Zn, Se, Cd, Pb during therapeutic abstinence from alcohol in 101 cases of alcoholism]. AB - The patients were subdivided into 3 groups, in accordance with clinical, echographic, laboratory and laparoscopy criteria: without liver disease, with liver disease and with alcoholic cirrhosis. In alcoholics with liver disease (with or without cirrhosis), we found a constant significant decrease in lead during abstinence, while in patients with cirrhosis zinc has a significant increase. Always lower to normal the blood selenium. The cadmium in the serum increases also after a month. PMID- 2599288 TI - [Acute rhabdomyolysis, myoglobinuria and renal insufficiency caused by ethanol: review of the literature and description of a clinical case with fatal outcome]. AB - Several studies demonstrated that alcohol can induce both chronic and acute myopathy with myoglobinuria. Acute rhabdomyolysis is commonly followed by a renal failure (R.F.) of variable degree. The Authors report a case of rhabdomyolysis induced acute R.F. in a chronic alcoholic young man. The patient died in irreversible shock. Early diagnosis of the disease seems to be important, because early treatment can prevent acute myoglobinuric R.F. PMID- 2599289 TI - [Recent knowledge on a new "marker" of bone metabolism: osteocalcin]. PMID- 2599290 TI - [Clinical case. Infectious mononucleosis]. PMID- 2599291 TI - Endoscopic treatment of biliary tract fistulas. AB - Endoscopic therapy was attempted in 24 patients with spontaneous or postoperative persistent biliary fistulas. Endoscopic retrograde cholangiography demonstrated the site of the fistula in 22 cases. Sphincterotomy or biliary stent placement resulted in rapid resolution of the fistula in 16 of 24 patients. Failures were attributed to exclusion of the injured intrahepatic bile duct in two cases, insufficient dilation of a bile duct stricture in one, the large size of the bile duct defect in two, and associated lesions in three (cirrhosis, arterial trauma, subhepatic abscess). Endoscopic management of biliary fistulae requires: (1) visualization of the location of the fistula by retrograde cholangiography especially in case of an intrahepatic lesion, (2) prior percutaneous drainage of associated subhepatic or subphrenic abscesses, and (3) appropriate relief of distal biliary obstruction in order to reduce the intraductal biliary pressure. The outcome is uncertain when endoprostheses are used to bridge large bile duct defects. PMID- 2599292 TI - The needle knife: a valuable tool in diagnostic and therapeutic ERCP. AB - Using monopolar electrocautery technique, we have used both an electrified guide wire and a needle-tipped sphincterotome to successfully enter the common bile duct, subsequently image it, and perform therapeutic procedures when by virtue of the patient's anatomy, or because of tumor, this had not been possible using conventional ERCP catheters. In an initial group of 45 patients using the needle tipped sphincterotome, clinically significant complications occurred in 3 patients but were not of a serious nature. The technique was an effective method for achieving both diagnostic ERCP and therapeutic maneuvers in 43 of 45 patients. We stress that this technique should only be attempted by those with long experience in ERCP and related procedures. PMID- 2599293 TI - Congestive gastroenteropathy--an extension of nonvariceal upper gastrointestinal bleeding in portal hypertension. AB - Three cirrhotic patients with acute and chronic gastrointestinal blood loss are described. All had extensive gastric mucosal changes on endoscopy consistent with congestive gastropathy and also had extensive duodenal and jejunal changes consisting of multiple friable punctate areas of erythema. Two patients had esophageal varices from which bleeding could not be documented. The mucosal abnormalities seen in the small intestine of all three patients were similar to those within the stomach and are thought to represent an extension of congestive gastropathy and to be contributing to the blood loss. We propose that the term "congestive gastropathy" be replaced by a more comprehensive term, "congestive gastroenteropathy." The cause of these mucosal abnormalities remains unclear. Attempts at endoscopic therapy of these extensive abnormalities should be avoided until a greater understanding of the underlying pathophysiology is reached. PMID- 2599294 TI - Upper gastrointestinal endoscopy findings in patients with long-standing bulimia nervosa. AB - Bulimia nervosa, an eating disorder now recognized with increasing frequency, is receiving growing attention because of purported complications. Recent claims of a high frequency of erosions, ulceration, and bleeding in the esophagus, ascribed to repeated, self-induced vomiting, prompted us to investigate by endoscopy the upper gastrointestinal mucosa in 37 consecutive patients with long-standing bulimia nervosa. The endoscopic appearance of esophageal and gastric mucosa was normal in 23 patients. Signs of mild esophagitis observed in eight patients were not related to the duration or severity of bulimic behavior or to symptoms of gastroesophageal reflux; two of these eight patients had sliding hiatal hernias. The remaining six patients were found to have superficial mucosal erythema in the stomach or duodenum, but none showed actual erosions, ulcers, or bleeding. Our observations suggest that, in contrast to reports by others, mucosal injury consequent to chronic, self-induced vomiting in patients with bulimia nervosa is relatively infrequent and limited. PMID- 2599295 TI - Hypoxia and tachycardia during endoscopic retrograde cholangiopancreatography: detection by pulse oximetry. AB - Oxygen saturation and pulse rate were recorded using pulse oximetry during 50 consecutive endoscopic retrograde cholangiopancreatography (ERCP) examinations. Oxygen saturation dropped to below 90% in 22 patients at some point during the procedure. Multiple regression analysis revealed that increasing age and weight were the most significant variables in predicting tachycardia or hypoxia. These problems cannot be reliably predicted or detected clinically. The use of a pulse oximeter during ERCP is recommended. PMID- 2599296 TI - Oxygen desaturation and changes in breathing pattern in patients undergoing colonoscopy and gastroscopy. AB - The respiratory effect of diagnostic colonoscopy and upper endoscopy were studied in 32 elderly patients. Twenty-two underwent colonoscopy and 10 upper endoscopy. In the group undergoing upper endoscopy, 4 of 10 patients experienced a decrease in oxygen desaturation greater than or equal to 4% during the medication period; an additional 2 patients desaturated during the procedure. In the group undergoing colonoscopy, 12 of 22 patients experienced oxygen desaturation during the medication period; 3 other patients desaturated during the procedure. Mean SaO2 for each group was lowest (p less than 0.05) during the medication period. Central apneas occurred in 13 of the patients undergoing colonoscopy during the medication period; however, only 8 of these patients with apneas experienced desaturation greater than or equal to 4% and the periods of desaturation did not correlate with the periods of apneas. Oxygen desaturation greater than or equal to 4% occurs frequently during both upper endoscopy and colonoscopy in this elderly population. This is related to the effects of sedation; the procedure itself worsened the desaturation in only 16% of the patients. Furthermore, the desaturation did not correlate with changes in the breathing patterns of the patients. Low-flow oxygen and/or close monitoring of patients during and subsequent to administration of medication is advised. PMID- 2599297 TI - A new light delivery system for the treatment of obstructing gastrointestinal cancers by photodynamic therapy. PMID- 2599298 TI - Dilators for esophageal stricture--a description of a new bougie and a comparison of current instruments. PMID- 2599299 TI - ERCP in a nonhuman primate. PMID- 2599300 TI - Portal venous gas secondary to a penetrating foreign body of the stomach. PMID- 2599301 TI - Intermittent biliary obstruction secondary to a mobile ampullary adenoma. PMID- 2599302 TI - Precut papillotomy--a risky technique for experts only. PMID- 2599303 TI - Upper gastrointestinal endoscopy without prior sedation. PMID- 2599304 TI - Upper gastrointestinal endoscopy without sedation. PMID- 2599305 TI - Percutaneous endoscopic duodenostomy: a misnomer? PMID- 2599306 TI - Take care with the tip of your video duodenoscope. PMID- 2599307 TI - Cytologic study of colonic lavage effluent in colonic adenocarcinoma. PMID- 2599308 TI - Non-instrumental small bowel perforation following upper gastrointestinal endoscopy. PMID- 2599309 TI - Jejunal perforation after esophagogastroscopy. PMID- 2599311 TI - The role of endoscopy in diseases of the biliary tract and pancreas. Guidelines for clinical application. PMID- 2599310 TI - Retroversion examination of the duodenal bulb. PMID- 2599312 TI - The role of endoscopic sclerotherapy in the management of variceal bleeding. Guidelines for clinical application. PMID- 2599313 TI - The efficacy of hypnosis in the treatment of dentin hypersensitivity. PMID- 2599314 TI - Effect of air-powder abrasive on glass ionomer microleakage. PMID- 2599315 TI - Eye protection and ocular complications in the dental office. PMID- 2599316 TI - Infection control in prosthodontics: a choice no longer. PMID- 2599317 TI - Essential criteria for treatment planning overdentures with attachments. PMID- 2599318 TI - Nitrous oxide: an update on problems and recommendations. PMID- 2599319 TI - Dentigerous cyst associated with an impacted mesiodens. PMID- 2599320 TI - Appendicitis induced by an endodontic file. PMID- 2599321 TI - Temporary stabilization of periodontally questionable teeth. PMID- 2599322 TI - Complete dentures with an acquired protrusive occlusion. PMID- 2599323 TI - Three-year results of a behavioral fear control program in a private dental office. PMID- 2599324 TI - Periodontal access techniques for restorative dentistry. PMID- 2599325 TI - The effect of the Caridex system on dentin permeability. PMID- 2599326 TI - Comparison of effects of ultrasonic and sonic instrumentation on amalgam restorations. PMID- 2599327 TI - Inhibition of supragingival calculus deposition by an experimental dentifrice. PMID- 2599328 TI - The incisal edge splint. PMID- 2599329 TI - Bupivacaine and lidocaine compared for postoperative pain control. PMID- 2599330 TI - Intraoral radiography for office-trained dental assistants: a model certification program. PMID- 2599331 TI - Unilateral localized juvenile periodontitis: a 2-year follow-up. PMID- 2599333 TI - Radiographs and the responsible dentist. PMID- 2599332 TI - Mandibular resorption and unilateral neuralgia of the inferior alveolar nerve. PMID- 2599334 TI - Treatment of an unusual instance of fusion with a talon cusp. PMID- 2599335 TI - A technique for providing interim occlusal support during segmental restoration. PMID- 2599337 TI - Dental radiographs and oral cancer. PMID- 2599336 TI - An in vitro investigation comparing the marginal leakage of Cavit, Cavit-G, and T.E.R.M. PMID- 2599339 TI - Burkitt's lymphoma. PMID- 2599338 TI - New challenges for the dental profession to contribute to the quality of life. PMID- 2599340 TI - Clinical experience with Chinese herbs in endodontic therapy. PMID- 2599341 TI - The rubber dam as a surgical drape: protection against AIDS and hepatitis. PMID- 2599342 TI - The effects of vasopressin and related peptides on osmoregulation in Amoeba proteus. AB - We describe the effects of arginine-vasopressin (AVP) and five related peptides on the contractile vacuole, the osmoregulatory organelle of the fresh water Amoeba proteus. Arginine-vasopressin, lysine-vasopressin, and SKF 101926, a synthetic antagonist of vasopressin, cause a significant increase in the rate of output of the contractile vacuole. Deamino-vasopressin (dAVP), oxytocin, and arginine-vasotocin have no such activity, although dAVP interferes with the action of AVP when present in equimolar concentration. Relatively high concentrations are required and the effect of active peptides is readily reversible. When the normal, hypotonic medium (a synthetic pond water) is replaced by isotonic sucrose, the action of AVP on the vacuole is abolished. Thus vasopressin is believed to act by increasing permeability of the Amoeba plasma membrane to water. PMID- 2599343 TI - Effects of castration on pituitary gonadotropic cells of the male three-spined stickleback, Gasterosteus aculeatus L., under long photoperiod in winter: indications for a positive feedback. AB - Male three-spined sticklebacks caught in winter were castrated or sham-operated and subsequently kept under long photoperiod at about 20 degrees for a month. With this treatment the sham-operated fish attained breeding condition. The gonadotropic cells of the sham-operated fish contained significantly more dilated endoplasmic reticulum and fewer granules than those of the castrated fish, indicating a higher secretory activity of the gonadotrops in the sham-operated fish. These findings suggest the existence of a physiological positive feedback within the gonadal-pituitary axis of the male stickleback when stimulated into its breeding condition by long photoperiod. PMID- 2599344 TI - Synthesis of 20 alpha-hydroxylated steroids by ovaries of the dab (Limanda limanda). AB - Dab (Limanda limanda) ovarian fragments were incubated in vitro with either [4,7 3H]pregnenolone or 17 alpha-hydroxy[1,2,6,7-3H]progesterone to investigate the pattern of steroidogenesis. A major enzyme found in the dab ovary was 20 alpha hydroxysteroid dehydrogenase. Among the steroids that were tentatively identified in ovarian incubates were 17 alpha,20 alpha-dihydroxy-4-pregnen-3-one (17,20 alpha-P). 17 alpha,20 alpha-dihydroxy-5 beta-pregnan-3-one, 3 beta, 17 alpha,20 alpha-trihydroxy-5 beta-pregnane (3 beta,17,20 alpha-P-5 beta), and 3 alpha,17 alpha,20 alpha-trihydroxy-5 beta-pregnane. The presence of these steroids in plasma of mature female and male dabs was studied by radioimmunoassay. The antiserum was raised against 17,20 alpha-P. The 17,20 alpha-[3H]P label was produced by incubating place milt with 17 alpha-hydroxy [3H]progesterone. The radioimmunoassay was shown to have a high cross-reaction with the 5 beta-reduced analogues of 17,20 alpha-P and was therefore used, in conjunction with thin-layer chromatography, to measure the steroids. High concentrations of both 17,20 alpha P and 3 beta,17,20 alpha-P-5 beta found in female and male dab plasma. The possible role of these steroids is discussed. PMID- 2599345 TI - Action of sex steroid hormones on temperature-induced sex determination in the snapping turtle (Chelydra serpentina). AB - Administration of exogenous estradiol benzoate (EB) or an estrogen agonist, R2858, into eggs of snapping turtles caused all embryos incubated at male producing temperatures to develop as females, whereas testosterone propionate (TP) caused 42% of the embryos to develop as females. Some of the embryos treated with EB, R2858, or TP also had hypertrophied oviducts. Neither dihydrotestosterone (DHT) nor cholesterol had any apparent effect on the sex determination of embryos incubated at male-producing temperatures. Injections of TP, DHT, the androgen agonist R1881, or cholesterol had no apparent effect on sex determination of embryos incubated at female-producing temperatures. Administration of estradiol antiserum or testosterone antiserum resulted in some individuals having undifferentiated or ambiguous gonads. Although both exogenous estrogens and androgens can induce embryonic gonads to develop as ovaries, the findings of this study indicate that estrogen is the female-inducing hormone and that androgens may feminize gonads via aromatization to estrogen. Furthermore, the results of the antisera injection suggest that endogenous steroid hormones may have a natural role in gonadal differentiation of reptiles with environmental sex determination. PMID- 2599346 TI - Dynamics of background adaptation in Xenopus laevis: role of catecholamines and melanophore-stimulating hormone. AB - The pars intermedia of the pituitary gland in Xenopus laevis secretes alpha melanophore-stimulating hormone (alpha-MSH), which causes dispersion of pigment in dermal melanophores in animals on a black background. In the present study we have determined plasma levels of alpha-MSH in animals undergoing adaptation to white and black backgrounds. Plasma values of black-adapted animals were high and decreased rapidly after transfer to a white background, as did the degree of pigment dispersion in dermal melanophores. Plasma MSH values of white-adapted animals were below the detection limit of our radioimmunoassay. Transfer of white animals to a black background resulted in complete dispersion of melanophore pigment within a few hours, but plasma MSH levels remained low for at least 24 hr. This discrepancy between plasma MSH and degree of pigment dispersion suggested the involvement of an additional factor for stimulating dispersion. Results of in vitro and in vivo experiments with receptor agonists and antagonists indicated that a beta-adrenergic mechanism, functioning at the level of the melanophore, is involved in the stimulation of pigment dispersion during the early stages of background adaptation. PMID- 2599347 TI - Secretory activity and postembryonic development of the tentacle sensory system controlling growth hormone-producing neurons in Lymnaea stagnalis. AB - The cerebral neuroendocrine peptidergic light green cells (LGC) of the freshwater snail Lymnaea stagnalis regulate body growth. The LGC are controlled by a tentacle sensory system that consists of two types (S1 and S2) of primary sensory neuron located at the base of each tentacle. Sensory (S2) axons make synaptic contacts (type A synapse-like structures) with the somata and axons of the LGC, where they release the contents of secretory granules, by exocytosis (demonstrated with the ultrastructural tannic acid-Ringer incubation method). Ultracytochemistry indicates that the granule contents are glycoproteinaceous. Furthermore, the S2 axons release secretory material in a nonsynaptic fashion into the interneuronal space of the central nervous system (CNS), at the level of the neuropiles of the cerebral ganglia and of the cerebral commissure. This release occurs by exocytosis from nonsynaptic release sites. It is proposed that the tentacle sensory system not only (synaptically) controls LGC activity but also influences other, remote neuronal targets in the CNS in a nonsynaptic ("at long distance," "paracrine," "hormone-like") fashion. Already in newly hatched snails (with a shell height of 1 mm) S2 axons show a fair rate of exocytotic activity, in both synaptic and nonsynaptic respects. During postembryonic development the secretory capacity of the S2 sensory neurons increases markedly, by increases in (1) the number of axons, (2) the size of the secretory granules, and (3) exocytosis activity. This increased capacity may meet a growing demand of the developing CNS, including the LGC, for neurochemical input from the tentacle sensory system. PMID- 2599348 TI - Corticosteroid biosynthesis in the interrenal cells of the teleost fish, Oreochromis mossambicus. AB - Applying high-performance liquid chromatography and thin-layer chromatography to separate corticosteroids, we studied the biosynthesis of steroids by the interrenal cells of the head kidneys (the adrenocortical homolog) of Oreochromis mossambicus. Intact head kidneys converted exogenous 17 alpha-hydroxyprogesterone into mainly cortisol, but 11-deoxycortisol, cortisone, and androstenedione were also recovered from the medium. Incubation of intact tissue with pregnenolone in addition resulted in the formation of large amounts of an unidentified product, which was absent in incubations of tissue homogenates with pregnenolone. PMID- 2599349 TI - Pituitary steroids in two teleost species: immunohistological and biochemical studies. AB - Antisera raised against steroid hormones [estradiol-17 beta (E2), testosterone (T), 11 beta-hydroxyandrostenedione (OHA)] were used to localize immunoreactive material in fixed and paraffin-embedded pituitaries of the African catfish and the rainbow trout. Organic extracts of pituitary homogenates were analyzed for steroid hormones by radioimmunoassay and gas chromatography-mass spectrometry (E2 in female catfish only). With the exception of an E2-positive cell type in the catfish neurointermediate lobe, steroid immunoreactivity was found to be restricted to the cytoplasm of adenohypophyseal cells, which were also labeled after incubation with catfish alpha,beta-gonadotropin and salmon gonadotropin antisera, respectively. Steroid levels determined by radioimmunoassay in the catfish ranged between 85 and 628 pg/pituitary, while lower levels (2-8 pg/pituitary) were found in the rainbow trout. E2 was identified by gas chromatography-mass spectrometry at a level of 84 pg/pituitary. The observation that immunolabeling after steroid antiserum incubation is confined mainly to gonadotrops provides morphological evidence for direct steroid effects on this particular cell type. PMID- 2599350 TI - Pregnenolone, testosterone, and estradiol in the migratory locust Locusta migratoria; a gas chromatographical-mass spectrometrical study. AB - Homogenates of ovaria as well as testes from the locust Locusta migratoria were analyzed for the presence of pregnenolone, testosterone, and estradiol by gas chromatography followed by mass spectrometry. Selected ion monitoring analyses revealed that the molecular ion and two characteristic fragment ions of pregnenolone, the molecular ion with its isotopes and two characteristic mass fragments of testosterone, and the molecular ion, its isotopes and four characteristic fragment ions of estradiol, were present at the proper retention times and with the correct abundance ratios. PMID- 2599351 TI - Partial purification of parathyrin from the corpuscles of Stannius (PCS) of the eel (Anguilla anguilla, L.). AB - It has been previously shown that the eel corpuscles of Stannius (CS) synthesize and secrete a substance (PCS) which is functionally and immunologically related to the mammalian parathyrin family. Purification of PCS, including anion-exchange chromatography, ODS C-18 reverse-phase HPLC, and affinity chromatography, showed that a biologically active peak, eluted in 32% acetonitrile, contains a 32- to 34 kDa protein which is 600-fold more potent than the crude extract is a test involving the hypocalcemic response in the CS-deprived eel. Specific immunoprecipitation of protein encoded by mRNA extracted from eel CS indicates that a 45-kDa precursor is involved in PCS synthesis. The hypothetical significance of a "large" parathyrin-like molecule in fish is suggested in relation to what is known about mammalian parathyrin gene expression. PMID- 2599352 TI - Electroporation induced transformation of Bacteroides ruminicola and Bacteroides uniformis by plasmid DNA. AB - Frequencies of greater than 10(5) transformants per microgram DNA were achieved in Bacteroides ruminicola F101 by electroporation of cells under anaerobic conditions, using the 19.5 kbp tetracycline resistance plasmid pRRI4. Similar procedures gave frequences of 10(6) erythromycin resistant transformants per microgram DNA with the shuttle plasmid pDP1 (19 kbp) in Bacteroides uniformis. Transformation of B. uniformis occurred at a far lower frequency (10(3) micrograms) when pDP1 DNA was derived from E. coli rather than B. uniformis. PMID- 2599353 TI - Plasmid-mediated resistance to fosfomycin in Staphylococcus epidermidis. AB - Staphylococcus epidermidis strain BM2641, isolated from a patient, was resistant to penicillin G, methicillin, aminoglycosides, chloramphenicol, macrolide, lincosamide and streptogramin B-type (MLS) antibiotics, and to high levels of fosmycin. Resistance to forsfomycin and/or to MLS was lost at low frequencies either spontaneously or after curing with novobiocin. The plasmid DNA from BM2641 and its cured derivatives was purified, analyzed by agarose gel electrophoresis and transferred to a nitrocellulose sheet. Comparative analysis of the resistance phenotypes with the plasmid content of the strains indicated that fosfomycin and MLS resistance were encoded by plasmids pIP1842 (2.5 kb) and pIP1843 (2.6 kb), respectively. Southern hybridization with a probe specific for gene fosA of Serratia marcescens showed that the fosfomycin resistance determinant in Staphylococcus is not homologous to that of Gram-negative bacteria. PMID- 2599354 TI - Purification and amino acid sequence of two small, acid-soluble proteins from Clostridium bifermentans spores. AB - Clostridium bifermentans spores contain two major small, acid-soluble, proteins (SASP) termed SASP-alpha and beta. The amino acid sequences of SASP-alpha and beta are almost identical, and are very similar to those of alpha/beta-type SASP from spores of C. perfringens and various Bacillus species. However, the C. bifermentans proteins contain an extra five amino acids in the middle of their sequence. Surprisingly, no gamma-type SASP were found in C. bifermentans or C. perfringens spores, although these are the most prominent SASP in spores of Bacillus species. PMID- 2599355 TI - Transformation of Bacillus amyloliquefaciens by electroporation. AB - A method for transformation of whole Bacillus amyloliquefaciens cells by electroporation was developed. The procedure is as efficient as the protoplast transformation method, resulting in up to 10(5) transformants/micrograms plasmid DNA, but requires less effort and time. Cells for electroporation were grown to late exponential phase in a rich medium supplemented with 0.25 M sucrose, washed with and resuspended in 0.25 M sucrose, 1 mM HEPES, 1 mM MgCl2, 10% (v/v) glycerol, pH 7.0, at 3-5 x 10(10) cells/ml for storage at -80 degrees C. The highest transformation frequency was obtained at 7.5 kV/cm with a 25 microF capacitor. The transformation efficiency increased linearly with DNA concentration at least over the range 10 ng-12.5 micrograms/ml. Transformations with ligated DNA and of industrial strains were also successful. In addition, B. subtilis cells treated as above could be transformed by electroporation, resulting in 10(4) transformants/micrograms DNA at 12.5 kV/cm. PMID- 2599356 TI - Lysis of erythrocytes by the secreted cysteine proteinase of Porphyromonas gingivalis W83. AB - The cysteine proteinase produced in the culture supernatant of Porphyromonas gingivalis was extensively purified. Haemagglutination type assays in which the enzyme was titrated against a fixed concentration of erythrocytes, showed that low levels of enzyme directly caused lysis of the red blood cells. However, using the same assay, the presence of stoichiometric amounts of the thiol blocking agent, 2,2'-dipyridyl disulphide (2-PDS) specifically inhibited the action of the enzyme or its haemagglutination with W83 cells or vesicles. In all cases, electron micrographs revealed that in the presence of 2-PDS the erythrocytes remained intact. Thiol activator free enzyme or aerated, inactivated enzyme had no effect on the red blood cells. These results show conclusively that the secreted cysteine proteinase of P. gingivalis causes lysis of erythrocytes and must now be regarded as a potent virulence determinant of P. gingivalis. PMID- 2599357 TI - The tsr gene-coding plasmid pIJ702 prevents thiopeptin from inhibiting ppGpp synthesis in Streptomyces lividans. AB - Streptomyces lividans normally accumulated high levels of ppGpp during nutritional shift-down. Its accumulation was, however, severely inhibited when a small amount of thiopeptin (an analogue of thiostrepton) was included in the transfer medium. In contrast, a S. lividans strain, which harbours the plasmid pIJ702 carrying the tsr gene resist to thiopeptin through methylation of the 23S rRNA, was still capable of accumulating ppGpp in the presence of large amounts of thiopeptin. These results indicate that the rRNA methylation resulting from the action of tsr gene prevents thiopeptin not only from inhibiting cell-growth but also from inhibiting ppGpp synthesis. The results also indicate that the observed accumulation of ppGpp during nutritional shift-down was associated with ribosomal function, as has been shown in E. coli and B. subtilis. PMID- 2599358 TI - Identification of N1-acetylnorspermidine in Vibrio parahaemolyticus and an enzyme activity responsible for its formation. AB - N1-Acetylnorspermidine [CH3CONH(CH2)3 NH(CH2)3NH3] was identified in Vibrio parahaemolyticus, which contains norspermidine as a major polyamine. This is the first example for the natural occurrence of monoacetylated unusual polyamine. The N1-acetylnorspermidine content was the highest 4 h after inoculation. Incubation of norspermidine and acetyl CoA with a cell extract from V. parahaemolyticus produced N1-acetylnorspermidine. A remarkable increase in specific activity of the acetyltransferase was observed at the exponential phase of growth. Spermidine also served as a substrate for the enzyme, with the formation of two isomers of the acetylspermidines (N1-acetylspermidine was predominant), but the reaction rate was less than 50% of that with norspermidine. These results suggest that norspermidine in V. parahaemolyticus may be associated with the cell growth and its role may be controlled through acetylation, as reported for spermidine in Escherichia coli. PMID- 2599359 TI - Relationships among Vibrio costicola strains assessed by DNA-DNA hybridization. AB - Deoxyribonucleic acid (DNA)-DNA hybridization was used to determine the relationships among 14 strains of Vibrio costicola isolated from cured meats or hypersaline waters. Our results indicate that the strains investigated should be considered members of the same genomic species, with homologies of 60% or higher with the V. costicola strains used as reference. Low DNA relatedness was found with other marine vibrios or moderately halophilic bacteria tested. The guanine plus-cytosine base contents of DNAs from the 14 V. costicola strains were 47.6 to 51.1 mol%. PMID- 2599360 TI - Plasmid analysis and antimicrobial susceptibilities of Peptostreptococcus species. AB - There are no published methods on plasmid isolation from Peptostreptococcus spp., therefore two methods of plasmid isolation from this genera were analysed: the boiling and alkaline-SDS methods. Plasmid DNA was not recovered by the boiling method, however, with the alkaline-SDS method, cryptic plasmid DNA was detected in two P. asaccharolyticus and one P. magnus strains. To achieve optimum lysis, Peptostreptococcus cells were treated with lysozyme (2 mg/ml) for 15 min. at 37 degrees C followed by proteinase K (0.2 mg/ml) for 1 h at 37 degrees C. In addition we report, the occurrence of clindamycin or metronidazole-resistant peptostreptococci, but these phenotypes were not correlated with plasmid carriage. PMID- 2599361 TI - Cloning and sequencing of the nifH gene of Desulfovibrio gigas. AB - The Desulfovibrio gigas nifH gene has been cloned and sequenced. It consists of an open-reading frame of 822 base pairs encoding a 274 amino acid polypeptide. A potential ntrA-dependent promotor sequence is present. The gene lacks an upstream activator sequence homologous to those often found in nif genes subject to activation by nifA. PMID- 2599362 TI - The cell envelope of Mycobacterium smegmatis: cytochemistry and architectural implications. AB - In sections stained for localizing both carbohydrates (Thiery's method) and lipids (the O.T.O. method), the cell envelope of Mycobacterium smegmatis appeared to consists of an asymmetric cytoplasmic membrane surrounded by a three-layered cell wall. The outer layer of the cytoplasmic membrane was found to contain more glycoconjugate molecules (probably phosphatidyl inositol mannosides) than the inner one. The cell wall consists of the peptidoglycan (the innermost layer) surrounded by a layer containing both arabinogalactan and mycolates (the electron dense layer), whereas the outermost layer was unstainable. There is clearly a difficulty in reconciling such a cell wall organization with the models so far proposed. PMID- 2599363 TI - A mutant hemolysin with lower biological activity produced by a mutant Vibrio parahaemolyticus. AB - A mutant toxin (m-TDH) of thermostable direct hemolysin (Vp-TDH) of Vibrio parahaemolyticus was isolated from the culture of a strain of this organism mutagenized with N-methyl-N'-nitro-N-nitrosoguanidine. Although the m-TDH had a molecular structure similar to the native Vp-TDH, the m-TDH retained only about 7% residual hemolytic activity of the native toxin. Furthermore, other biological activities of m-TDH, such as lethality in mice and enterotoxicity in rabbit ileal loops, were also weakened. The m-TDH was immunologically indistinguishable from the native Vp-TDH. These results suggest that the m-TDH is only slightly different in structure from the native Vp-TDH. Also, the mutagenized site in m TDH, which is not immunogenic, seems to be involved in expressing not only hemolytic activity but also lethal and enterotoxic activity. PMID- 2599364 TI - Genetic analysis of bacteriophage P22 lysozyme structure. AB - The suppression patterns of 11 phage P22 mutants bearing different amber mutations in the gene encoding lysozyme (19) were determined on six different amber suppressor strains. Of the 60 resulting single amino acid substitutions, 18 resulted in defects in lysozyme activity at 30 degrees; an additional seven were defective at 40 degrees. Revertants were isolated on the "missuppressing" hosts following UV mutagenesis; they were screened to distinguish primary- from second site revertants. It was found that second-site revertants were recovered with greater efficiency if the UV-irradiated phage stocks were passaged through an intermediate host in liquid culture rather than plated directly on the nonpermissive host. Eleven second-site revertants (isolated as suppressors of five deleterious substitutions) were sequenced: four were intragenic, five extragenic; three of the extragenic revertants were found to have alterations near and upstream from gene 19, in gene 13. Lysozyme genes from the intragenic revertant phages were introduced into unmutagenized P22, and found to confer the revertant plating phenotype. PMID- 2599365 TI - Conversion of deletions during recombination in pneumococcal transformation. AB - Genetic analysis of 16 deletions obtained in the amiA locus of pneumococcus is described. When present on donor DNA, all deletions increased drastically the frequency of wild-type recombinants in two-point crosses. This effect was maximal for deletions longer than 200 bases. It was reduced for heterologies shorter than 76 bases and did not exist for very short deletions. In three-point crosses in which the deletion was localized between two point mutations, we demonstrated that this excess of wild-type recombinants was the result of a genetic conversion. This conversion extended over several scores of bases outside the deletion. Conversion takes place during the heteroduplex stage of recombination. Therefore, in pneumococcal transformation, long heterologies participated in this heteroduplex configuration. As this conversion did not require an active DNA polymerase A gene it is proposed that the mechanism of conversion is not a DNA repair synthesis but involves breakage and ligation between DNA molecules. Conversion of deletions did not require the Hex system of correction of mismatched bases. It differs also from localized conversion. It appears that it is a process that evolved to correct errors of replication which lead to long heterologies and which are not eliminated by other systems. PMID- 2599366 TI - Interactions between pesticide genes: model and experiment. AB - In response to years of intense selection pressure by organophosphate insecticides, several different insecticide resistance mechanisms have evolved in natural populations of the mosquito Culex pipiens. We examined interactions between two of the most important mechanisms using a four-compartment model of insecticide pharmacokinetics. The joint effect of different mechanisms of resistance can be expressed in terms of epistasis at the physiological level in this model. The type of epistasis predicted by the model depends on the particular physiological mechanisms of resistance involved. Resistance due to a reduced penetration of the insecticide combines multiplicatively with other resistance factors, but resistance due to detoxicative processes and to insensitivity of the target site combines additively. How the pattern of epistasis at the physiological level is translated into fitness epistasis in natural populations of this mosquito depends on the intensity and pattern of insecticide selection in the field. PMID- 2599367 TI - No linkage between genes controlling female pheromone production and male pheromone response in the European corn borer, Ostrinia nubilalis Hubner (Lepidoptera; Pyralidae). AB - The E and Z pheromonal strains of the European corn borer, Ostrinia nubilalis, are characterized by female production of and male preference for opposite blends of (E)-11-and (Z)-11-tetradecenyl acetate. It is known that the pheromone production is controlled by an autosomal gene and that the males' behavior is determined by a sex-linked gene. A third gene, autosomally inherited, has been shown to determine the organization of the male pheromone receptors. In the present study the linkage relationship between the autosomal genes controlling sex pheromone production and male olfactory sensilla was investigated. A recombination experiment showed unequivocally that the genes determining the variation in pheromone production and male pheromone receptors are not closely linked and are most likely inherited independently. PMID- 2599368 TI - Time for spreading of compensatory mutations under gene duplication. AB - Evolution by compensatory mutations is accelerated by gene duplication because selective constraint is relaxed by gene redundancy. A mutation is called compensatory if it corrects the effect of an earlier deleterious mutation. Without duplication, Kimura has shown that the time for spreading of compensatory mutations is much reduced by tight linkage between the two chromosomal sites of mutations. In this report, the time for spreading with gene duplication was studied by using the diffusion equation method of Kimura, together with computer simulations. It was shown that, when 2Nv- is much less than unity, the time for spreading is greatly shortened by gene duplication as compared with the case of complete linkage between the two sites of mutations, where 2N is the effective population size (haploid) and v- is the rate of compensatory mutations. However, if 2Nv- greater than 1, gene duplication is not effective for accelerating the evolution by such mutations. PMID- 2599369 TI - The effect of change in population size on DNA polymorphism. AB - The expected number of segregating sites and the expectation of the average number of nucleotide differences among DNA sequences randomly sampled from a population, which is not in equilibrium, have been developed. The results obtained indicate that, in the case where the population size has changed drastically, the number of segregating sites is influenced by the size of the current population more strongly than is the average number of nucleotide differences, while the average number of nucleotide differences is affected by the size of the original population more severely than is the number of segregating sites. The results also indicate that the average number of nucleotide differences is affected by a population bottleneck more strongly than is the number of segregating sites. PMID- 2599371 TI - Estimating the variability of substitution rates. AB - Suppose that amino acid or nucleotide data are available for a homologous gene in several species which diverged from a common ancestor at about the same time and that substitution rates between all pairs of species are calculated, correcting as necessary for multiple substitutions and for back and parallel substitutions. The variances and covariances of these corrected substitution rates are evaluated, and are used to construct a new test for uniformity (constancy of the molecular clock) and to find the best estimates of substitution rates in individual lineages with their standard errors. A substantial bias may arise if the effect of correcting the pairwise substitution rates is ignored. PMID- 2599370 TI - A cladistic measure of gene flow inferred from the phylogenies of alleles. AB - A method for estimating the average level of gene flow among populations is introduced. The method provides an estimate of Nm, where N is the size of each local population in an island model and m is the migration rate. This method depends on knowing the phylogeny of the nonrecombining segments of DNA that are sampled. Given the phylogeny, the geographic location from which each sample is drawn is treated as multistate character with one state for each geographic location. A parsimony criterion applied to the evolution of this character on the phylogeny provides the minimum number of migration events consistent with the phylogeny. Extensive simulations show that the distribution of this minimum number is a simple function of Nm. Assuming the phylogeny is accurately estimated, this method provides an estimate of Nm that is as nearly as accurate as estimates obtained using FST and other statistics when Nm is moderate. Two examples of the use of this method with mitochondrial DNA data are presented. PMID- 2599372 TI - [Study of morphology and genome structure of Pseudomonas putida bacteriophages for their classification]. AB - A group of 27 bacteriophages specific for Pseudomonas putida strains PpG1 and PpN has been isolated. The phages were characterized and compared with the previously described virulent (pf 16, af, tf and PMW) and temperate (PP56 and PP71) phages. The new phages belong to B1 and C1 morphotypes, according to Ackerman's classification. Phage DNAs were digested with several endonucleases; the molecular weights and homology of the DNAs were determined. All phages of P. putida isolated up to now were distributed into 10 species (groups), on the basis of particle morphology, genome size and the results of homology studies. Recombination processes are believed to participate in formation of phages belonging to certain species. PMID- 2599373 TI - [Restriction-modification systems of type II in Shigella strains]. AB - Two restriction-modification systems specified by two plasmids are discovered in the clinical species of Shigella. The plasmids are designated pKMR114 and pKMR115. Both are of 60.800 bp and belong to the IncN incompatibility group. The EcoRI, EcoRV, HindIII restriction patterns of both plasmid DNAs are identical. As shown by efficiency of plating of bacteriophage lambda vir on the strains harbouring plasmids encoding EcoRI, EcoRII, EcoRIII, EcoRIV, EcoRV systems and plasmids studied, the discovered plasmids control synthesis of EcoRII specificity enzymes. The main distinctive feature of the pKMR114 is the ability to decrease efficiency of plating of bacteriophage T4 having glycolised DNA. PMID- 2599374 TI - [Genetic analysis of complementation of t-haplotypes in mice]. AB - Complementation for viability of the compounds tx/ty in complete lethal haplotypes t6, t12, tw5, tw12, tw18, tw73, twPa-1 belonging to the seven basic complementation groups was studied. In the overwhelming majority of crosses a lack of tx/ty offspring was revealed but there is also evidence of non-complete complementation of the tx/ty haplotypes, except for T/tw73XT/tw12, T/tw18XT/t12, T/tw73XT/tw18 crosses in which the level of complementation for viability exceeds 100%. The maternal effect for compound variability was significantly revealed in 9 out of the 19 matings. In addition, reciprocal matings of heterozygotes T/txXT/ty were tested for fertility. In two cases, the maternal effect was also revealed for this character. Comparison of data on viability of the compounds and the fertility of the original strains gives grounds to believe that the tx/ty haplotypes are not completely recessive and partially manifest themselves in the heterozygotes, decreasing fertility in a number of matings. In some cases, these t-haplotypes yield an effect, close to negative complementation, which may be associated with the interaction of the proteins of t-haplotypes. PMID- 2599375 TI - [Phenogenetic analysis of various changes in the color of fur in silver foxes originated during domestication]. AB - Quantitative and qualitative analysis of pigmentation in "singne"-type fur color mutation arising in silver foxes during domestication, was made. It was shown that the decrease in quantity of eumelanine in hair and uneven distribution of pigment granules lengthwise the hair were the reason for formation of "singnes". PMID- 2599376 TI - [Mechanisms of reproductive compensation in populations with different types of reproduction]. AB - Reproductive compensation mechanisms have been studied in two populations with different reproductive behaviour. In populations with natural reproductive behaviour mechanism of reproductive compensation was shown to be the shortening of the mean intergenetic interval in the female group having excessive (as compared with the mean population value) failures in their pregnancy outcomes (spontaneous abortions, still-births, prereproductive age deaths of children). In family planning populations, however, reproductive compensation mechanisms are: deliberate shortening of the intergenetic interval after pregnancy failure only and deliberate prolongation of actual reproduction. In family planning populations the proportion of females bearing at over 35 was shown to double, due to reproductive compensation. PMID- 2599377 TI - [Evolution of Alu repeats: dynamics of distribution in genome]. AB - A mathematical model of evolutionary dynamics of Alu repeats' number in the human genome has been worked out. The model permitted us to observe the dynamics of propagation of Alu repeats within the genome and to evaluate such important parameters of the process mentioned as the rates of transposition (insertion of new copies into the genome) and excision of repeats. The peculiarities of the control of Alu repeats' number in the genome have been discussed, based on the data obtained. PMID- 2599378 TI - [Theoretical analysis of mechanisms of spontaneous and induced mutations in DNA based on repeated sequences]. AB - Mechanisms of spontaneous and chemically induced point mutations' emergence in DNA have theoretically been investigated using the statistical weight method. We have analysed 12 nucleotide sequences containing 95 point spontaneous mutations and 3 sequences comprising 30 mutations induced by such mutagens as 4' hydroxymethyl-4,5',8-threemethylpsoralene, natrium bisulfite, hydroxylamine. The possibility of occurrence of point mutations by repair correction of heteroduplexes formed via mispairing of imperfect direct and inverted repeats in DNA has been studied. Statistically reliable connection of position of spontaneous mutations in DNA with repeats has been revealed for a number of nucleotide sequences. Statistically reliable connection of mutations induced by 4'-hydroxymethyl-4,5',8-threemethylpsoralene with imperfect repeats is also shown. PMID- 2599379 TI - New gene arrangements in natural populations of Drosophila subobscura. AB - Four new gene arrangements were detected in natural populations of Drosophila subobscura near Zurich, Switzerland. Three of them are the result of inversions not recorded before, and one is a new combination of known gene arrangements. Another arrangement, I3 + 4, was recorded for the first time in Switzerland. It may have been imported or possibly may have arisen de novo. It is suggested that inversion mutations are not so infrequent as so far supposed, if the presence of mobile elements is taken into account in D. subobscura. PMID- 2599380 TI - Near-normal chiasma formation and maintenance in a short distal translocated segment in maize. AB - Study of successful crossover pairing and chiasma formation is informatively extended to a very short translocated segment. Contrary to previous suggestion it now seems likely that the extreme distal region of the long arm of maize chromosome 1 is not deficient in intrinsic capacity for the initiation of crossover pairing. In addition, chiasmata formed in this short region appear to be efficiently maintained. PMID- 2599381 TI - An extreme allele of hooded spotting in the Norway rat. AB - A new allele (he) of hooded white spotting is described. The typical homozygous phenotype is an almost or completely white rat. The almost white animals have variable coloured spots on the sides of the head, usually around or above the eyes or covering the ears. Superficially, the eyes are dark but careful examination shows that pupil glows a dull red in bright illumination in all or the majority of individuals. PMID- 2599382 TI - Inheritance of coat colour in the Anatolian shepherd dog. AB - The predominant colour of the Anatolian Shepherd dog varies from a dark fawn to light red, with a variable black muzzle and face (mask). Evidence is presented that the colour is due to the dominant yellow allele (Ay) of the agouti locus. Two other frequent colours are white spotting, due to the piebald allele (sp), and the chinchilla allele (ch). Two rarer colours are the agouti wolf-grey wild type (A+) and a light fawn with a blue facial mask, due to the dilution allele (d). PMID- 2599383 TI - Inter- and intra-individual chromosome variability in Thamnomys (Grammomys) gazellae (Rodentia, Muridae) B-chromosomes and structural heteromorphisms. AB - The present paper reports intra- and inter-individual variability related to the occurrence of numerous B-chromosomes in Thamnomys (Grammomys) gazellae, a species of African Climber rat belonging to the 'dolichurus' group. The frequency of B chromosomes in somatic and spermatogonial metaphases is investigated, together with their behaviour during meiosis. Moreover, G-banding makes it possible to identify a structural polymorphism resulting from a pericentric inversion in a large chromosome (no. 6). The distribution of the constitutive heterochromatin has been assessed by C-banding. The nucleolus organizer regions (NOR's) were located by means of silver staining in four chromosomal pairs (nos. 1, 2, 4, and 6). The karyotype of T. (G.) gazellae is compared with that of other taxa of the dolichurus group, particularly the Somaliland population which also exhibits the occurrence of B-chromosomes. The origin and significance of B-chromosomes is discussed. PMID- 2599384 TI - [Homes for the aged and nursing homes in the Steiermark (Austria)]. PMID- 2599385 TI - The germ-spectrum problem and antibiotic-resistance in Bida and Minna hospitals- Nigeria. AB - In the present paper the occurrence of different species of Pseudomonas, of Acinetobacter calcoaceticum var. anitratum and Aeromonas hydrophila in hospitals is described. The possible human pathogenic significance is discussed. PMID- 2599386 TI - A contribution to the situation of antibiotic resistance in Abeokuta (Ogunstate) and Minna (Nigerstate) in Nigeria. AB - After testing various chemotherapeutics the following conclusions could be drawn: Pseudomonas was sensitive only to gentamicin. Gentamicin, aminopenicilline + calvulanacid and cefoxitin were 100% effective against E. coli. Gentamicin also proved effective against Enterobacter (83%). Cefoxitin, aminopenicillin + clavulanacid, gentamicin and trimethoprim + sulfonamide were effective against Klebsiella. Concerning Proteus sp., cefoxitin showed best results (100%). Acinetobacter was 100% inhibited by gentamicin. Gentamicin was most effective (93% sensitivity) against Staph. aureus. Trimethoprim + sulfonamide and erythromycine showed resistance rate of 17%, cefalosporine and isoxazolylpenicilline a rate of 21%. Aminopenicillin and aminopenicilline + calvulanacid were most suitable against Enterococcus (100%). PMID- 2599387 TI - A survey of leptospirological studies carried out on the Cape Verde Islands. AB - The authors subjected 611 human sera, 1295 sera of domestic and 211 sera of wild living animals from two islands of the Cape Verde archipelago to serological tests for leptospirosis. Among the human sera 7.2% reacted positively. Antibodies to L. bratislava of the serogroup Australis were most frequent (59.1% of all positive sera). Antibodies to L. icterohaemorrhagiae were found in 1.3% of the sera tested, to L. sejroe in 1.1%, to L. canicola in 0.7%, to L. pyrogenes in 0.3% and to L. pomona, L. bulgarica and L. grippotyphosa in 0.2% each. The existence of natural foci of leptospiroses could not be proved since tests of 211 wild-living mammals were all negative. The investigation of domestic animal sera showed a positivity of 3.1% with goats being positive most frequently (85% of all positive sera), followed by donkeys with 3.3% and cattle with 2.0%. Sera of dogs, sheep and pigs were all negative. The results indicate that anthropurgic foci exist on the Cape Verde Islands. PMID- 2599388 TI - Leptospirosis in the Melut district--upper Nile province (south Sudan)--an overview. AB - The authors examined 195 domestic animals for leptospirosis serologically in Sudan (170 cattle, 7 sheep and 18 goats) and 771 wild animals (36 species) with 13 serovars from 13 serogroups. 54% of domestic animals namely, 108 cattle and 1 sheep were positive in titer levels of 1:400 and higher. Cattle sera with the serovars of the serogroup Icterohaemorrhagiae were 2.4% positive with Cynopteri 2.4%, Autumnalis 3.5%, Australis 1.2%, Pomona 2.9%, Grippotyphosa 2.9%, Hebdonadis 17.1%, Bataviae 9.4% and Tarassovi 50.6%. Only one Numida meleagris of the 54 wild birds (14 species) was positive in low titer level of 1:100 with L. canicola. Seventy (9.8%) of the 717 wild mammals (22 species) examined were positive namely with the serovars of the serogroups Icterohaemorrhagiae 3.4%, Javanica 3.0%, Pomona 2.0%, Grippotyphosa 0.7%, Hebdomadis 0.4%, Ballum, Australis, Pyrogenes, Bataviae each 0.3% and Cynopteri 0.1%, whereby sera from 7 animals reacted simultaneously with the serovars of two serogroups. With regard to the species, positive reactions were found in Erinaceus albiventris, Eidolon helbum, Cercopithecus aethiops, Genetta spec., Canis adustus et aurus, Felis silvestris, Leptailurus serval, Arvicanthis niloticus, Mastomys spec., Mus spec., Gazella spec., Tragelaphus spec. The positivity in rodents was very low - 1.2%. PMID- 2599389 TI - Serological investigations of children in Iran for Campylobacter, Yersinia and Shigella. AB - Serological investigations for Campylobacter, Yersinia and Shigella in hospitalized children (different hospitals) in Iran revealed a contamination rate of 15% for Campylobacter, up to 19% for Yersinia and between 1 and 12% for the various strains of Shigellae. In diarrhoeal diseases the possibility of an infection with Campylobacter, Yersinia and Shigellae must be considered. PMID- 2599390 TI - The presence of ornithosis antibodies in Teheran's "city"-pigeons. AB - In Teheran, wild town pigeons were investigated for ornithosis showing a contamination rate of 46%. PMID- 2599391 TI - The presence of Q-fever antibodies in Teheran's pigeons (Columba domestica). AB - Teheran's wild city pigeons were tested for Q-fever antibodies. 12 out of 152 sera showed a positive reaction. PMID- 2599392 TI - [North-South--a future, a common task. North-South dialog of the Austrian Rectors' Conference, sphere of action "Science and research", activity field "Human medicine". 1]. PMID- 2599393 TI - [Work results of activity field 2 "Human medicine". Science and education for the development cooperation, 13 and 14 June 1988 in Vienna. 2]. PMID- 2599395 TI - [Study of the effect of noise of varying intensity and duration on human body by using mathematical planning]. AB - Human noise effect of various intensity and duration was studied. Mathematical models of noise effect on some physiological functions were calculated. It was established that specific noise effect on hearing analyzer was governed by its intensity. The character of noise effect on the central nervous system depended on the activation initial level. It was shown that nonspecific noise effect on the cardiovascular system was the function of exposure duration. PMID- 2599394 TI - [Hygienic substantiation of the information and energy models of variable noise]. AB - The results of the technological studies and chamber experiment provided the basis for the conception according to which noise information parameters contributed to its biologic activity identically with energetic characteristics. The calculation results obtained by the regression model showed that noise MAC with account of its information value should be at least 5-10 dBA less than the existing ones. Information parameters should also be regulated. PMID- 2599396 TI - [Effect of small doses of toxic substances and noise on the reproductive function of young animals]. AB - Possible combined effect of toluene and isopropylbenzene in concentrations of 0.5 of MAC was experimentally studied along with their combined effect with noise at the permissible for adolescents level IIC-65 on the reproductive function of white rats. The animals had been exposed to a complex of factors for 120 and 15 days prior to the appearance of pregnancy. The data thus obtained demonstrated the possibility of the appearance of the reproductive function impairments in young female workers after their short-term occupational exposure to the above factors and indicated the necessity of the development of effective preventive measures. PMID- 2599397 TI - [Hygienic standardization of physical factors generated by civil aviation in residential areas]. AB - The study was designed to analyze the hygienic characteristics of civil aircraft institutions (airports, facilities for air traffic safety control, meteorological service) as the main sources of electromagnetic energy and noise at the adjacent residential territory. The problems of hygienic standardization of electromagnetic emission in the radio frequency range of 4-9 produced by various radio engineering airport devices were studied together with other physical environmental factors (noise, temperature). Methodological approaches to the regulation of the above factors on the basis of hygienic standards were proposed. PMID- 2599398 TI - [Hygienic evaluation and the problems of standardization of magnetic fields with the frequency of 50 Hz]. AB - It is established that some kinds of technological equipment are the sources of the magnetic fields with the frequency of 50 Hz, their biologic activity being identified. Hygienic classification and approaches to differentiated standardization of the above factor are suggested with account of time and energetic parameters. PMID- 2599399 TI - [Hygienic evaluation of low-frequency magnetic fields of complex spectral composition]. AB - As illustrated by electrical domestic appliances, it is demonstrated that existing variable magnetic fields of the sources using industrial current can to a great extent be nonmonochromatic and possess rather a complex spectral composition. Under the above conditions the root-mean-square value of the magnetic field intensity used at present for meteorologic certification of the sources is unacceptable for hygienic assessment of the existing external magnetic fields. It is established that the root-mean-square value of the rate of the field induction variations representing the degree of body interaction with the electric field induced by the variable magnetic field is regarded as a more adequate and universal characteristic of low-frequency magnetic fields. PMID- 2599400 TI - [Functional status of the developing body as a criterion of hygienic standardization of electromagnetic fields of 2750 MHz]. AB - Elevated sensitivity of the developing organism of nonmature animals (white rats) to the exposure of the electromagnetic field (EMF) of 2750 mHz was established. Taking that into account, a hygienic standard for EMF of 2750 mHz was set up for the population at the level of 15 mWt/cm2. PMID- 2599401 TI - [Scientific basis of hygienic evaluation and regulation of physical environmental factors]. PMID- 2599402 TI - [Experimental analysis of biological effects of microwaves: their systemic, ultrastructural and neuronal mechanisms]. AB - For 200 hours the cats were exposed to microwaves of 2375 mHz, the energy current density being 500 mWt/cm2. 6 diversions of the electrocorticogram and multi cellular activity were registered by coal electrodes. After the exposure an electro-microscopic study of the lateral hypothalamic brain field was carried out. Under the radiation effect synchronization of slow bioelectric activity over the range of 6-10 to 12-16 took place. The analysis of the conditional probability matrix of series generation of action potential in the studied structures demonstrated their functional separation according to multi-cellular activity parameters in proportion to exposure growth. Damage of axodendritic synapses which provided morphologic links between brain structures was considered its morphologic substrate. PMID- 2599403 TI - [Standardization of environmental electromagnetic fields generated by meteorological radars]. AB - An analysis of some traditional techniques for the determination of the non working level of electromagnetic radiation of meteorological radars is provided. New approaches with higher strictness of definition and formalism are proposed. PMID- 2599404 TI - [Cytogenetic indicators as the criteria of hygienic evaluation of the effect of static electric field and ion currents]. PMID- 2599405 TI - [Study of the dynamics of low levels of air ionization in work places]. PMID- 2599406 TI - [Changes in the intensity of magnetic fields during contact electric welding]. PMID- 2599407 TI - [Calculation of risk probability in hygienic standardization of electromagnetic fields]. PMID- 2599408 TI - [Hygienic evaluation of noise from mine ventilators in residential areas]. PMID- 2599409 TI - [Noise-protective housing construction as a measure of the control of aircraft noise]. PMID- 2599410 TI - [Physiological criteria of evaluation of the functional status of the central nervous system in hygienic standardization of the electric field of industrial frequency]. PMID- 2599411 TI - [The role of multiple physical environmental factors on health of the population]. AB - Physical factors of urban environment (noise, electromagnetic fields) affect the process of the pathology development in children exposed to their effect at all the levels starting from the onset of early deviations in body nonspecific protection indices and up to the formation of chronic pathology. It has been established that all physical environmental factors negatively affect practically all the analyzed health indicators because of their nonspecific influence. At the same time it is demonstrated that the same factors have the most distinct effect on this or that system. Thus it becomes possible to exercise goal-oriented planning of environmental protection measures. PMID- 2599412 TI - [Changes in enzyme activity of the lymphocytes in animals in the evaluation of the adaptive reactions to electromagnetic fields of industrial frequency]. PMID- 2599413 TI - [Functional asymmetry as an indicator of the biological effect of ultrahigh frequency electromagnetic fields]. PMID- 2599414 TI - [Use of the parameters of the locomotor activity of animals in experimental and hygienic studies of microwave radiation]. PMID- 2599415 TI - [Adaptive reactions of the oxygen transport system of the blood after exposure to microwave radiation]. PMID- 2599416 TI - [Informative value of various biochemical indicators in the evaluation of the effects on the body of variable magnetic and electric fields of low and industrial frequencies]. PMID- 2599417 TI - [Analysis of the flow of Soviet publications on the biological effect of electromagnetic fields of radio frequency]. PMID- 2599418 TI - The biomedical blues. PMID- 2599419 TI - Day care programs and research challenges. PMID- 2599420 TI - Liberation: alternative to physical restraints. PMID- 2599421 TI - Treatment choices at the end of life: a comparison of decisions by older patients and their physician-selected proxies. AB - Doctors are increasingly faced with the ethical dilemma of making end-of-life medical care decisions for older patients who are decisionally incapacitated. Most often, they rely on family to assist them in choosing what the patient would have wanted. In this vignette-based study, the ability of proxies to choose as the patients reported they would have chosen is called into question. Implications for the use of advance directives for end-of-life care and avenues for needed research are discussed. PMID- 2599422 TI - Decision-making ability and advance directive preferences in nursing home patients and proxies. AB - We studied 39 nursing home patients and proxies to assess their decision-making capability and preferences regarding advance directives (ADs) or "living wills." Most patients willingly stated preferences; over half opted to forego burdensome measures when death appeared imminent. Patients perceived as decisionally capable were more likely to forego life-sustaining measures than those of questionable capability. The vast majority of proxies disapproved of using life-sustaining measures, even in some cases with limited knowledge of patients' preferences. PMID- 2599423 TI - Models of adult day care: findings from a national survey. AB - We examined a nationally representative sample of 60 adult day care centers to describe the state of this evolving care modality after a decade's growth. Results indicate that day care centers can be categorized into three models of care, each of which serves a distinctive subpopulation. Model appropriateness was tested with analysis of variance of differences in participant characteristics. Services, staffing, costs, and other program features are contrasted among the three models. PMID- 2599424 TI - Social behavior and physical restraints. AB - This paper addresses the question: Are physical restraints related to decreased social behavior among nursing home residents? Data collected from 112 nursing home residents suggest that low social performance puts a resident at risk of being restrained, but more frequently the use of a restraint hampers a resident's performance of social behavior. PMID- 2599425 TI - Failure to thrive: paradigm for the frail elder. AB - A retrospective study of 82 elderly "failure to thrive" (FTT) inpatients suggests that FTT is diagnosed when the elderly patient's functional ability to live with multisystem diseases, cope with the ensuing problems, and manage his/her own care are remarkably diminished and no longer responsive to health care interventions. In an attempt to clarify the clinical picture of FTT, we used standardized questionnaires to abstract data from medical charts. PMID- 2599426 TI - Financial strain and health of unmarried older people. AB - In a study of 1,782 older unmarried persons, we found no evidence that financial strain contributed to poor health. We examined the effect of financial strain on physical health over time and the degree to which vulnerability to financial strain was linked to health. PMID- 2599427 TI - Visual barriers to prevent ambulatory Alzheimer's patients from exiting through an emergency door. AB - Mobility combined with impaired mental functioning presents safety risks for Alzheimer's patients and poses an ethical dilemma for staff. This study, conducted on an Alzheimer's unit, tested seven different visual barrier conditions for reducing patient exists. Findings indicate that exiting was eliminated under two conditions. The results suggest visual agnosia, the inability to interpret what the eye sees, may be utilized as a tool in managing wandering behavior of Alzheimer's patients. PMID- 2599428 TI - The Caregiver Information Project: a mechanism to assist religious leaders to help family caregivers. AB - The Caregiver Information Project trained 200 clergy, lay religious volunteers, and social service providers about caregiving issues and ways to disseminate information to family caregivers. The project succeeded in improving knowledge about aging and caregiver issues, increased perceived competence in working with family caregivers, and stimulated the development of caregiver programs and activities. PMID- 2599429 TI - Economic blinkers in retirement research. PMID- 2599430 TI - Unscientific tendencies in health care research? PMID- 2599432 TI - Trip the light fantastic--a lesson in how to write a clinical tip. PMID- 2599431 TI - Language of aging or ageism? PMID- 2599433 TI - The use of osseous grafts in periodontics: are they safe? Do they work? PMID- 2599434 TI - Dr. Brendan C. Stack: an interview with the 1988 AAFO Man of the Year. Interview by Craig Stoner. PMID- 2599435 TI - The vertical overbite domino rule. PMID- 2599436 TI - Orthodontic diagnosis. Part 1: Skeletal. PMID- 2599437 TI - Heartburn--the acid test. AB - To determine whether symptoms of gastro-oesophageal reflux are related to the degree of oesophageal acid exposure, 190 patients (of 220 referred) with heartburn and acid regurgitation were compared with 50 normal subjects. A definite relationship between frequency of reflux symptoms and degree of oesophageal acid exposure was found both in patients with and without oesophagitis. We conclude that the frequency of gastro-oesophageal reflux symptoms is related to degree of oesophageal acid exposure. PMID- 2599438 TI - Physical characteristics of indigestible solids affect emptying from the fasting human stomach. AB - Gastric emptying of indigestible solids depends on their size. It is not clear whether physical characteristics other than particle size affect emptying of indigestible solids from the fasting human stomach. We studied gastric emptying of three differently shaped particles, (cubes, spheres, rods) of either hard or soft consistency during the fasting state in human volunteers. The shape of indigestible particles did not affect their emptying. The area under the gastric emptying curve (AUC: particles x hour) was for hard cubes 24.7 (2.2), for hard spheres 27.9 (1.6), for hard rods 26.9 (2.7). All soft particles emptied faster than their identically shaped hard counterparts, but there was no difference among the three shapes (AUC for soft cubes: 29.2 (3.0), for soft spheres 32.0 (1.8), for soft rods 34.1 (1.2). If gastric emptying of hard and soft particles was compared independently of their shape, soft particles emptied significantly faster than hard ones: AUC 31.8 (1.2) v 26.5 (1.3) (p less than 0.01). In conclusion, the consistency but not the shape significantly affects gastric emptying. Specific physical characteristics other than size and shape may affect gastric emptying of indigestible particles which may be of importance in the design of drugs. PMID- 2599439 TI - Stress and oesophageal motility in normal subjects and patients with irritable bowel syndrome. AB - Patterns of oesophageal motility were recorded in 17 healthy volunteers and 12 patients with the irritable bowel syndrome. Recordings were taken at rest and under stress by hyperventilation, a dichotic hearing challenge and a cold pressor test. In healthy volunteers the dichotic hearing challenge was associated with a significant increase in the mean amplitude of oesophageal peristalsis from 69.9 mmHg to 82.4 mmHg (p less than 0.01) and in the percentage of simultaneous waves from 9.7% to 24.5% (p less than 0.01). The cold pressor test increased the peristaltic amplitude from 69.9 mmHg to 87.1 mmHg (p less than 0.001) and the percentage of simultaneous waves from 9.7% to 34.4% (p less than 0.01). Both manoeuvres were associated with increases in pulse and blood pressure. In patients with irritable bowel syndrome, the resting mean oesophageal peristaltic amplitude was higher than that seen in normal volunteers (95.9 mmHg v 69.9 mmHg p less than 0.05). Changes in oesophageal motility during stress were similar in these patients to those seen in normal subjects although the changes were not significant. This study refutes the hypothesis that symptoms of irritable bowel syndrome and their association with stress are attributable to increased sensitivity of oesophageal motility to disruption by stressful stimuli. PMID- 2599440 TI - Effect of sucralfate on gastric mucosal blood flow in rats. AB - Sucralfate possesses site protective and cytoprotective actions and heals ulcers effectively, but its effect on gastric mucosal blood flow is unknown. Using an ex vivo gastric chamber preparation, we studied the effect of sucralfate on gastric mucosal blood flow in rats by laser doppler flowmetry. Under both fasting and fed states, measurements of gastric mucosal blood flow and damage were made in rats after topical application of absolute ethanol alone or after pretreatment with sucralfate. Gastric mucosal damage was assessed by measuring the total area of haemorrhagic mucosal lesions. Ethanol induced gastric mucosal lesions were significantly less with sucralfate pretreatment than without (p less than 0.008). Mucosal blood flow significantly fell after ethanol application (p less than 0.001). The fall was significantly less in fed than in fasted rats (p less than 0.05), and after pretreatment with sucralfate 100 mg or 200 mg than without in both fasted (p less than 0.0008 and 0.00001, respectively) and fed (p less than 0.002 and 0.001, respectively) rats. Graded doses of sucralfate (25-400 mg) resulted in an increase in gastric mucosal blood flow in a dose dependent manner (r = 0.731, p less than 0.001). In conclusion that sucralfate increases gastric mucosal blood flow in rats and lessens the fall in blood flow in rats treated with ethanol, and this action may contribute to its protection against the vascular damage of mucosa by ethanol. PMID- 2599441 TI - Prospective comparative study of the influence of postoperative bile reflux on gastric mucosal histology and Campylobacter pylori infection. AB - Biopsies of 17 peptic ulcer patients, randomly treated by partial gastrectomy with either Billroth-II (n = 9) or Roux-en-Y (n = 8) anastomosis were studied before and six months after surgery to determine the role of bile reflux in the early postoperative histological alterations of the gastric mucosa. After BII gastrectomy bile acid reflux (median 16.1 mumol/h) was significantly higher (p less than 0.0001) than after RY-gastrectomy (0.1 mumol/h). Campylobacter pylori was present in the preoperative biopsies of all 17 patients. After RY-gastrectomy biopsies of all eight patients were positive for Campylobacter pylori, but was detected in only five of the nine patients with BII-gastrectomy. Preoperative scores of gastritis grading were similar in both groups and no significant differences were found postoperatively. Gastritis scores of the anastomotic mucosa in patients with BII-gastrectomy were significantly higher (p less than 0.02) than in the RY-gastrectomy group. Moreover, the reflux gastritis score in the four BII-gastrectomy patients cleared from Campylobacter pylori was significantly higher (p less than 0.02) than in the postgastrectomy patients harbouring Campylobacter pylori. The results suggest that reflux gastritis and Campylobacter pylori related gastritis are distinct microscopic entities and that bile reflux may play a role in the eradication of Campylobacter pylori after gastrectomy. PMID- 2599442 TI - Cancer occurrence in a cohort of patients treated with cimetidine. AB - The possible carcinogenic effects of antisecretory agents used in the treatment of gastric and duodenal ulcer were investigated in a population based cohort study of 16,739 patients who were prescribed the H2-antagonist cimetidine between 1977 and 1981. An excess risk for gastric cancer was observed, with a relative risk of about 10 in the first year after beginning use of the drug, which decreased thereafter. A similar pattern was seen for cancers of the colon, pancreas and gall bladder, and for non-Hodgkin's lymphoma. These increased risks probably represent cases in which a malignancy was misdiagnosed as a gastric ulcer. The excess risk for gastric cancer was unaffected by the method of diagnosis, the risk in those who had undergone an endoscopy being similar to those who had been diagnosed by an x-ray examination. A relative risk of 1.5-2.0 was observed for cancer of the respiratory organs, with no effect of latency, indicating that there are common risk factors for peptic ulcer and for lung cancer. Although the observed increases in cancer risk in persons receiving cimetidine is probably caused by factors other than a carcinogenic action of the drug itself, this possibility cannot be ruled out because of the short period of follow up. PMID- 2599443 TI - Complement activation within the coeliac small intestine is localised to Brunner's glands. AB - Complement activation may play an important role in the pathogenesis of coeliac disease. In the present study immunohistochemical localisation of C3 and of a neoantigen exposed only on the terminal C5b-9 complement complex has been performed on small intestinal biopsy sections from newly diagnosed untreated coeliac patients, from coeliac patients on long-term gluten-free diet and from disease controls. Levels of C3 were markedly increased in treated coeliac patients compared with controls. Staining of C3 was concentrated subepithelially and within the centre of the lamina propria. No staining was detected at these sites using antibody to the neoantigen, however, strongly suggesting that the increased levels of C3 seen in the coeliac patients was the result of increased extravasation of serum proteins rather than complement activation. Surprisingly, complement activation was detected within the glands of Brunner. Positive staining using anti-C5b-9 neoantigen was found in all coeliac patients, both treated and untreated. Three of the 13 disease controls also showed reactivity with this antibody. This novel finding suggests that Brunner's glands, hitherto largely neglected structures, may play an important role in the development of coeliac disease. PMID- 2599445 TI - Cancer and the Peutz-Jeghers syndrome. AB - Among 72 patients with the Peutz-Jeghers syndrome malignant tumours have developed in 16 (22%) of whom all but one have died. There were nine gastrointestinal and seven nongastrointestinal tumours. The relative risks of death from gastrointestinal cancer and all cancers were 13 (95% CI 2.7-38.1) and 9 (95% CI 4.2-17.3) respectively. The chance of dying of cancer by the age of 57 was 48%. There is evidence for a hamartoma/carcinoma sequence in the Peutz Jeghers syndrome, suggesting that the gene locus involved is relevant to the development of malignancy in general. PMID- 2599444 TI - Raised number of jejunal IgG2-producing cells in untreated adult coeliac disease compared with food allergy. AB - The subclass distribution of IgG-producing immunocytes was studied by two colour immunohistochemistry with monoclonal antibodies in jejunal biopsy specimens from 10 adults with untreated coeliac disease, 11 coeliac disease patients on a gluten free diet, and seven patients with established food allergy. Paired immunofluorescence staining was performed with subclass specific murine monoclonal antibodies in combination with polyclonal rabbit antibody reagent to total IgG; the proportion of cells belonging to each subclass could thereby be determined. The ratio of IgG2 immunocytes was significantly higher (p less than 0.05) in untreated coeliac disease patients (median, 35.2%; range, 26.7-65.2%) than in those on a gluten free diet (median, 7.3%; range, 0-31.9%) or those having food allergy (median, 12.5%; range, 0-36.5%). The disparity in the local IgG2 response between patients with untreated coeliac disease and those with food allergy might be due to differences in the nature of the antigenic stimuli, dissimilar genetic 'make-up' of the subjects, or both. PMID- 2599447 TI - Dietary treatment of chylous ascites in yellow nail syndrome. AB - Chylous ascites has rarely been reported in yellow nail syndrome. A case of chylous ascites in yellow nail syndrome is described which was treated successfully with dietary restriction of fat and supplements of medium chained triglycerides. PMID- 2599446 TI - Induction of pancreatic tumours by longterm duodenogastric reflux. AB - The incidence of pancreatic cancer is increased in patients who have undergone gastric surgery. An animal model is described in which pancreatic hyperplasia and adenoma formation developed within 56 weeks. The effects of a simple gastrojejunostomy were compared with those after a split gastrojejunostomy, in which the jejunum was transected and the two limbs implanted separately into the greater curvature of the glandular stomach 1 cm apart. After 56 weeks no animals in the simple gastrojejunostomy group had pancreatic hyperplasia whereas all 10 animals in the split gastrojejunostomy group had generalised pancreatic hyperplasia with macroscopic nodules. Microscopy of the nodules showed that in nine animals hyperplastic nodules had developed, and four of these also had adenomatous nodules. The remaining animal had enlarged lymph nodes. Pancreatic hyperplasia was associated with jejunal hyperplasia. Jejunal morphometry showed that the villus height was doubled and the villus height:crypt depth ratio was higher in the split gastrojejunostomy group compared with those animals with a simple gastrojejunostomy. This finding represents a new model for the investigation of pancreatic neoplastic change. PMID- 2599448 TI - Giant fibrovascular polyp of the oesophagus: report of a case and effects on oesophageal function. AB - A 40 year old man with dysphagia and a giant fibrovascular polyp of the oesophagus is reported. The patient was followed for two years before removal of the polyp. During this period the tumour markedly increased in size and the oesophagus reached a maximum diameter of 5.9 cm. In presence of the polyp the body of the oesophagus had no pressure activity after swallows and a 22 hour intraoesophageal pH record showed pH greater than 7 for 31.4% of the time and never pH less than 4. After excision of the tumour the oesophagus regained normal size and peristalsis. Intraoesophageal pH greater than 7 and less than 4 were recorded for 1.6% and 16.1% of the time respectively. Dysmotility was probably a contributing factor to the genesis of dysphagia induced by the giant fibrovascular polyp. Prolonged alkalinisation of intraoesophageal pH conceivably reflected altered oesophageal clearing of alkaline salivary and/or oesophageal secretions. PMID- 2599450 TI - 14C-urea breath test for C pylori. PMID- 2599449 TI - Effect of information leaflets on knowledge in patients with gastrointestinal diseases. AB - Twelve patient information leaflets concerning common gastrointestinal diseases were produced by the British Digestive Foundation and evaluated to determine whether patients knew more about their disease if they received a leaflet. Eleven hundred and fifty patients attending gastroenterology clinics in the United Kingdom were assessed by postal questionnaire of whom half had received a leaflet relevant to their diagnosis six weeks before assessment. Seven hundred and fifty one replied (398 leafleted, 353 non-leafleted). Most patients found the leaflets helpful and easy to understand; few found them worrying. They were regarded as a better source of information than doctors, particularly for information about the characteristics of the illness and side effects of treatment. In all diagnostic groups assessed the patients' knowledge of their disease was significantly greater if they had received a leaflet than if they had not. Individual responses by patients without leaflets showed that fundamental misconceptions persisted about digestive diseases. The British Digestive Foundation leaflets are an effective means of imparting disease related information to patients. PMID- 2599451 TI - The iceberg of ethics. PMID- 2599452 TI - Antacid alert. PMID- 2599453 TI - Home safe home. Practical tips for fall-proofing. PMID- 2599454 TI - Head injury perils. PMID- 2599455 TI - From life care to professional care. PMID- 2599456 TI - A rose is still a rose. PMID- 2599459 TI - Primary squamous carcinoma of the ovary. PMID- 2599457 TI - The right environment for Alzheimer's. PMID- 2599458 TI - AIDS cases rejected by nursing homes. PMID- 2599460 TI - The inherent cellular radiosensitivity of epithelial ovarian carcinoma. AB - Ovarian carcinomas of similar histology have variable responses to radiation therapy. It has been suggested that inherent cellular resistance to radiation may in part underlie radiotherapy failure. To determine in vitro radiobiological parameters of papillary serous adenocarcinoma of the ovary, we investigated the cellular responses of 16 early-passage ovarian carcinoma cell lines to radiation. The radiosensitivity, as measured by D0, ranged from 1.05 to 2.40 Gy (mean 1.70 Gy), and, as measured by D, ranged from 1.65 to 3.54 Gy (mean 2.38 Gy). The extrapolation number -n ranged from 1.1 to 2.0 (mean 1.5). The cells had a 1.3- to 5.4-fold (mean 2.8) ability to recover from potential lethal damage (PLDR) 24 hr after irradiation and subculture from plateau-phase cultures. Their inherent radioresistance may be one factor in the failure of some ovarian cancers to be sterilized by radiation. PMID- 2599461 TI - Predictive value of multiple tumor marker assays in second-look procedures for ovarian cancer. AB - Sera from 51 ovarian cancer patients in clinical remission undergoing a second look operation were studied. CA 125, CA 15-3, and 90K assays were performed in the week preceding surgery. Twenty-seven patients (53%) had no evidence of disease; 3 (6%) and 21 (41%) had microscopic and macroscopic disease. All patients but two with no evidence of disease had normal CA 125 serum levels, as did the three cases with microscopic disease and 6 patients with macroscopically detectable tumor. Of 17 patients with high CA 125 values, 15 (88%) were found to have persistent disease. Hence, the sensitivity and specificity of a CA 125 assay were 62 and 93%, respectively. CA 15-3 levels were low in all patients with no evidence of disease, in 2 cases with microscopic disease, and in 2 cases with residual tumor greater than 1 cm. All patients with high CA 15-3 titers had a positive second-look. The sensitivity and specificity of assay were 69 and 100%, respectively. With the 90K assay, 4 false-positive and 4 false-negative results were found and the sensitivity and specificity were 69 and 67%, respectively. However, 3 of 4 cases with a false-positive 90K assay had recurrence of disease with 7, 9, and 20 months later. Combination of the three markers increased sensitivity to 79%. These data suggest that more effective surveillance of disease status at second-look is obtained by using a combination of tumor marker assays. PMID- 2599462 TI - Comparison of repeat smear, colposcopy, and colposcopically directed biopsy in the evaluation of the mildly abnormal smear. AB - Repeat smear, colposcopy, and colposcopically directed biopsy were performed in 161 patients referred to our department because of a Pap smear showing mild dysplasia (CIN 1). Colposcopically directed biopsies revealed the presence of CIN of different grades in 61 cases (37.5%). In 33 (20.4%) the CIN grade found at biopsy was higher than 1. Repeat smear confirmed the presence of CIN 1 in 67 women (47.2%). In this group of patients colposcopically directed biopsies showed a CIN grade greater than 1 in 12 cases (17.9%). The repeat smear was negative in 59 patients (41.5%). In this group, biopsy showed varying grades of neoplasia in 12 cases. Colposcopic examination indicated no dysplasia but the presence of minor cervical abnormalities in 76 women (47.2%): at biopsy a CIN grade higher than 1 was found in 9 cases (11.5%). These data suggest that the mildly atypical smear identifies a group of patients at increased risk of CIN but gives little or no information on the disease severity. Repeat smear and colposcopic examination alone appear inadequate to demonstrate the severity of the cervical lesion. Due to the high proportion of CIN 2 and 3 in patients with a mildly abnormal smear, the systematic biopsy of any colposcopically abnormal area seems essential to proper management of the patient. PMID- 2599464 TI - Splenectomy during primary maximal cytoreductive surgery for epithelial ovarian cancer. AB - Six patients with epithelial ovarian cancer underwent splenectomy as part of their extensive primary cytoreductive surgical management at the Johannesburg University Hospital. These patients represented 7.6% (6 of 79) of advanced disease patients (stages III and IV) followed during the study period. Five splenectomies were performed because of metastatic disease confirmed on microscopy. One of these showed parenchymal involvement and represented only the third case in the world literature. The remaining patient required splenectomy for capsular avulsion injury and resultant bleeding. Late thrombotic complications occurred in 4 of 6 (67%) patients, resulting in death of one patient from massive pulmonary embolism 20 days after surgery. Three patients (50%) currently have no evidence of disease 14, 25, and 32 months after surgery. The remaining 2 patients died of recurrent disease 19 and 58 months following primary operation. This, the largest reported series in the English literature, indicates that splenectomy, albeit potentially hazardous, is justified when it permits optimal cytoreductive surgery. PMID- 2599463 TI - Comparison of short-lived high-LET alpha-emitting radionuclides lead-212 and bismuth-212 to low-LET X-rays on ovarian carcinoma. AB - We are investigating the potential use of short-lived alpha-emitting radionuclides for the treatment of ovarian carcinoma. These radionuclides transfer dense high ionizing linear energy (high LET) over a short path length without dependence upon cellular oxygen. The alpha-emitting radionuclides chosen were lead-212 and bismuth-212 which are readily available. The radiosensitivities of two ovarian carcinoma cell lines (OVC-1 and OVC-2) was greater with 212Pb and 212Bi than with X-ray therapy. D0, inversely related to the radiosensitivity, was 155 and 240 rads for OVC-1 and OVC-2, respectively. With 212Pb or 212Bi, the slope of the survival curves was steeper. The D0 was 75 and 70 rads after 212Pb and 85 and 95 rads after 212Bi treatment for OVC-1 and OVC-2, respectively. The relative biological effectiveness with alpha irradiation was two to four times greater than with X rays. Unlike low-LET irradiation (i.e., X rays and gamma emitters) the cells had no ability to accumulate or repair sublethal damage. From these experiments it is concluded that a greater therapeutic advantage may be gained with alpha-emitting radionuclides than X rays. Further development of these nuclides may provide for a new form of therapy. PMID- 2599465 TI - Whole-abdomen radiation therapy in ovarian carcinoma: its role as a salvage therapeutic modality. AB - A significant proportion of patients with epithelial ovarian carcinoma eventually fail after initial responses to chemotherapy. Further treatment with chemotherapy consisting of either the same combination or second-line regimens has been ineffective in producing durable responses. Thus, between June 1983 and June 1987, thirty patients with epithelial ovarian carcinoma who failed one or more chemotherapeutic regimens were treated with whole-abdominopelvic-cavity radiation therapy. Prior to the radiation the amount of residual disease after debulking was noted to be microscopic in 16 patients and macroscopic in 14 patients. Radiation was delivered with an open-field technique that extended from the domes of the diaphragm to the obturator foramina. Doses of 2500 cGy were planned to the whole abdomen, with a boost of another 2500 cGy to the pelvic and or paraaortic nodes when indicated. Higher doses were delivered to the areas of gross disease in the pelvis. Only 2 patients were unable to complete the planned therapy. Another 26% of the patients required interruption of the therapy secondary to hematologic toxicity but eventually completed the treatment. With an overall median follow-up of 14 months, 56% of the patients remain alive. Two-year actuarial survival and recurrence-free survival rates are 47 and 32%, respectively. The survival and recurrence-free survival rates for the group with microscopic residual disease--61 and 33%, respectively--are better than those for the patients with macroscopic residual disease--36 and 18%. The abdominopelvic cavity was the first site of failure in all but one of the 17 patients who have failed. In spite of the higher doses, pelvic failure alone or as a component occurred in 54% of the patients. Small bowel obstruction necessitating surgical intervention as a complication of therapy was seen in 13% of the patients. PMID- 2599466 TI - A prospective surgical pathological study of stage I squamous carcinoma of the cervix: a Gynecologic Oncology Group Study. AB - Thirty-three institutions collaborating in the Gynecologic Oncology Group gathered surgical and pathological data on 1125 patients with primary, previously untreated, histologically confirmed stage I cervical carcinoma with more than 3 mm of invasion who were selected to undergo radical hysterectomy and paraaortic and pelvic lymphadenectomy. Of the 940 eligible, evaluable patients, 732 had squamous carcinoma. Of the study group, 87 (12%) did not undergo radical hysterectomy because of gross disease beyond the uterus or microscopic aortic node involvement documented at exploratory laparotomy. Among the 645 patients undergoing pelvic and paraaortic lymphadenectomy and radical hysterectomy, five risk factors were significantly associated with microscopic pelvic lymph node metastasis: depth of invasion (P = 0.0001), parametrial involvement (P = 0.0001), capillary-lymphatic space invasion (P = 0.0001), tumor grade (P = 0.01), and gross versus occult primary tumor (P = 0.009). The factors identified as independent risk factors for pelvic lymph node metastasis by multivariate analysis were capillary-lymphatic space involvement (P less than 0.0001), depth of invasion (P less than 0.0001), parametrial involvement (P = 0.0005), and age (P = 0.02). The model was used to predict the chance of a patient having nodal metastasis for any combination of risk factors. PMID- 2599468 TI - Resection of diaphragmatic peritoneum and muscle: role in cytoreductive surgery for ovarian cancer. AB - Fourteen patients undergoing primary cytoreductive surgery for stage III ovarian malignancies had diaphragmatic peritoneum, muscle, or both resected in an attempt to remove all metastatic disease greater than 0.5 cm in diameter. Resection was completed in 13 of 14 patients (93%), all obtaining optimal cytoreduction. Size of resected specimens varied from 12 x 7 to 17 x 11 cm. The mediastinum was entered in two patients. Four patients had resection of diaphragmatic muscle. All defects were closed primarily and a thoracostomy tube was placed. One patient who did not have muscle resection had a 30% pneumothorax that spontaneously resolved. No subdiaphragmatic hematomas or abscesses occurred. Time (mean 65 min, range 40 150 min) and blood loss (mean 175 ml, range 100-1500 ml) for the surgery depended upon extent of disease. One procedure was terminated due to bleeding from a lacerated liver capsule. We conclude that diaphragmatic peritoneum/muscle resection can be completed successfully with acceptable morbidity. PMID- 2599467 TI - Prognostic value of the rupture of the capsule in stage I epithelial ovarian carcinoma. AB - The prognostic influence of the integrity or the rupture of the capsule was examined in 60 patients with stage I epithelial ovarian carcinoma. After an average follow-up of 75 months (range 30-120 months) the probability of 5-year survival was 76% in both groups. Therefore, we conclude that rupture of the tumor during surgery has no influence on survival rates. Consequently, these patients should not be considered as belonging to the subgroup stage IC ovarian carcinoma, as suggested by the FIGO committee. PMID- 2599469 TI - Postoperative pain management in gynecology oncology patients utilizing epidural opiate analgesia and patient-controlled analgesia. AB - Intraoperative analgesia is the purview of anesthesiologists whereas postoperative pain is traditionally managed by surgeons. This series reports 19 months experience of anesthesiologists using epidural opiate analgesia (EOA) or patient-controlled analgesia (PCA) to treat postoperative pain in 302 patients following surgery for pelvic malignancy. For the 244 (81%) patients who received EOA, a lumbar epidural catheter was placed just prior to surgery, injected with local anesthetic for intraoperative analgesia, and injected with preservative free morphine at appropriate intervals postoperatively to relieve pain. Fifty eight patients (19%) used PCA which consisted of small self-administered boluses of intravenous narcotics. All patients were seen daily to ensure adequate analgesia and to treat side effects. Utilizing a 0-10 verbal rating scale (0 = no pain; 10 = worst pain imaginable), mean pain with EOA was 0.75 at rest and 2.6 with coughing. Mean pain ratings with PCA were 2.8 at rest and 5.0 during coughing. Side effects with EOA included nausea or vomiting (28%) and pruritus (20%). The only side effect of significance with PCA was nausea or vomiting (21%). All patients improved with treatment of side effects. Acceptance of these techniques is indicated by a steady increase in the number of gynecologic oncology surgical patients utilizing these modalities (50% at the outset to 87% currently). PMID- 2599470 TI - Ovarian management at the time of radical hysterectomy for cancer of the cervix. AB - Ovarian management at the time of radical hysterectomy for cervical cancer was reviewed retrospectively over a 7-year period. All patients had early-stage cancer except three who had stage IIB disease. Approximately 80% of patients had squamous cancer and 20% adenocarcinoma or adenosquamous carcinoma. The mean age was 44, and 24% of patients were 35 or younger. Ninety-nine patients had their ovaries removed. None of the ovaries contained metastatic disease including 22 patients with adenocarcinoma or adenosquamous carcinoma. Of the 17 patients with retained ovaries 14 had transposition into the paracolic gutters. Only one of the 14 patients with transposed ovaries developed symptoms of ovarian failure. No patients with retained ovaries developed metastatic disease or required reoperation secondary to new ovarian pathology. It is our opinion that normal ovaries can be preserved in young women at the time of radical hysterectomy for early cervical cancer regardless of histologic type. PMID- 2599471 TI - Conservative surgical management of superficially invasive stage I vulvar carcinoma. AB - Fifty patients with stage I squamous cell carcinoma of the vulva were treated by means of wide local excision and either unilateral or bilateral superficial inguinal lymphadenectomy. Depth of invasion per se was not an exclusionary criterion; however, 36 of 37 patients for whom depth of invasion could be assessed had tumors invasive to a maximum depth of 5 mm. Factors investigated included recurrences and survival in addition to the early and delayed morbidity associated with this operative approach. Recurrent intraepithelial or minimally invasive cancer was documented in six patients, five of whom were treated successfully by a subsequent wide local excision following initial surgery. Only one patient died of recurrent carcinoma 16 months following surgery. The morbidity with this operation was appreciably less than that generally reported with more extensive operations commonly employed in the management of vulvar cancer and is recommended for management of patients with early invasive disease. PMID- 2599472 TI - Significance of positive endocervical curettage in predicting endocervical canal involvement in patients with cervical intraepithelial neoplasia. AB - A total of 108 patients with positive endocervical curettage who underwent cone biopsy were carefully examined to determine the accuracy of endocervical curettage (ECC) in predicting endocervical canal involvement with cervical intraepithelial neoplasia (CIN). The data suggest a 63% correlation between positive ECC and endocervical canal involvement: 72.4% of patients with CIN III on cervical biopsy had endocervical canal involvement compared to 27.3% who had CIN I. Two patients with positive ECC were found to have invasive cancer on cone biopsy. PMID- 2599473 TI - Management of early endometrial carcinoma. AB - Management of early endometrial carcinoma is controversial in regard to timing and indication of adjunctive radiation therapy. Two hundred eighty patients with stage I carcinoma of the endometrium are analyzed: 135 patients were treated with surgery only and 61 patients underwent preoperative and 83 patients postoperative radiation therapy. The overall survival was 94%. Recurrence rates in all three treatment arms were equal. Tumor grade was found to change from the diagnostic D&C specimen to the definite surgical specimen in 31% of all cases and in 50% of all grade 3 lesions. As only 39% of all patients required postoperative radiation therapy with equal survival, a primary surgical approach spares the majority of patient unnecessary treatment and preserves prognostically important histology. PMID- 2599474 TI - Immunohistochemical investigations of steroid receptors in normal and neoplastic squamous epithelium of the uterine cervix. AB - The proliferation of squamous cells of the vagina and cervix uteri is induced by steroid hormones during the menstrual cycle. However, carcinoma of the cervix cannot be influenced by any hormone therapy. Forty-four different cervical specimens (different days in the menstrual cycle of healthy women and those with dysplastic lesions and carcinomas of the cervix) have been tested for estrogen (ER) and progesterone (PR) receptor protein content by means of immunohistochemistry. The ER content of the squamous epithelium depends upon the menstrual cycle: in the early proliferative phase cells of all layers are negative. In the midphase of proliferation the basal and parabasal layers become positive, and in the secretory phase positive cell nuclei can be found up to the superficial layers. A weak reaction to ER staining is found only in mild dysplastic lesions of the uterine cervix; severe dysplastic forms and invasive carcinomas were all negative. No positive PR was found in any squamous cell tissue. Stroma cells of the uterine cervix showed different straining intensity for ER and PR, regardless of the menstrual cycle. The loss of ER in the neoplastic cell could be an explanation for three clinical experiences: premenopausal patients have no tumor progression of the cervix uteri despite normal ovarian function; the duration of survival shows no relation to the receptor status of cervical carcinomas; and antihormonal treatment of cervical carcinomas produces no appreciable therapeutic success. PMID- 2599475 TI - Second-look laparotomy in the patient with minimal residual stage III ovarian cancer (a Gynecologic Oncology Group Study). AB - One hundred eighty-six patients with minimal residual Stage III ovarian cancer (tumor mass less than or equal to 3 cm) were treated in a prospective randomized protocol (melphalan with or without Corynebacterium parvum). As per protocol 84 patients were eligible and underwent a second-look laparotomy with 41 (49%) having negative findings for persistent malignancy. Factors which affected survival after second look were presence or absence of macroscopic disease, age, and grade. Depending upon these prognostic factors, survival at 4 years after second look ranged from 31 to 100%. The role of second-look laparotomy is examined relative to these results. PMID- 2599476 TI - Recurrent vulvar carcinoma in the intervening tissue bridge in early invasive stage I disease treated by radical vulvectomy and bilateral groin dissection through separate incisions. AB - Early invasive stage I squamous cell carcinoma of the vulva treated with radical vulvectomy and bilateral inguinofemoral lymphadenectomy rarely recurs, particularly when the lymph nodes contain no metastatic tumor. Primary radical surgery in this patient utilized separate groin incisions, and recurrent tumor developed in the tissue bridge between the groin scar and the vulva. Reexploration showed numerous inguinofemoral nodes to subseqently contain recurrent carcinoma. Literature regarding early, "microinvasive," squamous cell carcinoma of the vulva is reviewed. PMID- 2599477 TI - Metastatic adenocarcinoma of the cervix presenting as an inflammatory breast lesion. AB - The occurrence of an inflammatory breast lesion and wide-spread venous thrombosis in a woman with metastatic adenocarcinoma of the endocervix is reported. Examination of biopsy specimens showed the inflammatory breast mass to be histologically consistent with metastasis from the endocervix. Recurrent venous thrombosis requiring large doses of heparin for control of the phlebitis was also a feature of this patient's illness. The disease was associated with elevation of serum CA 125 levels that did not parallel the patient's clinical course. PMID- 2599478 TI - [Contraception behavior of abortion patients]. PMID- 2599479 TI - [Endometriosis as the main or concomitant finding in fertility surgery. A retrospective study]. PMID- 2599480 TI - Evaluating programs in health care settings. PMID- 2599481 TI - Group therapy with moderately neurologically damaged patients. AB - The diagnosis and psychosocial treatment of moderately head injured clients requires three elements. First, there should be a stated frame of reference for the understanding of client behavior within the constraints of the injury. Second, and related to the first, there should be at work a practice theory that is consistent with the therapist's view of human behavior. Third, interventions must be consistent with both. In this article, the authors describe and discuss all three needed elements. The membership perspective serves as the practice theory and as the foundation for the operationalization of group therapy with the head injured client. PMID- 2599482 TI - Perspectives on depression among black Americans. AB - Although research shows a prevalence of depression among black as well as white Americans, black Americans do not seek or receive treatment to an equal extent. Social workers should become better educated about depression and develop skills in recognizing this illness. Outreach efforts are needed to increase black Americans' awareness of depression and of the availability of treatment. Through development of ethnically sensitive mental health services and through working relationships with physicians, social workers can contribute to the identification of depressive symptoms, which can help avoid misdiagnosis. PMID- 2599483 TI - Life review as a therapeutic frame in the treatment of young adults with AIDS. AB - In this article, the author describes developmental and clinical issues in the use of life review as a therapeutic frame in psychotherapy of young adults with acquired immune deficiency syndrome. Presentation of clinical data suggests that elaboration of life narratives, by means of reminiscence, may help people to regain a cohesive sense of self, carry out psychological and social tasks, and revise life structures in the context of the illness experience. The author demonstrates how narrative approaches, informed by developmental theory, shift the focus from disability and dysfunction to concern for relative health and personal growth in social intervention with this population. Emergent research issues also are identified. PMID- 2599484 TI - Integrating research with practice: the psychosocial impact of breast cancer. AB - Social workers collecting data in this study of the psychosocial impact of breast cancer not only gained insights into clinical efforts and program planning, but also had opportunities for clinical intervention. Empirical results from the study, as well as practice models implemented based on these results, are presented. This model integrating research with practice holds considerable potential for enhancing social work practice. PMID- 2599485 TI - Monitoring patient outcome following discharge: a computerized geriatric case management system. AB - Many political, economic, and social factors are influencing health care providers to consider case-management programs. The authors describe a computer supported, hospital-based case management program for elderly patients and report on the benefits and drawbacks of the program. Primary benefits include access to better client data, improved discharge planning capabilities, and greater program efficiency. Drawbacks chiefly are related to the difficulties inherent in introducing computerization into a human service setting. Overall, the program is a beneficial addition to patient care efforts and is a valuable tool for tracking high-risk patients in acute-care settings. PMID- 2599486 TI - Social environment and adjustment after laryngectomy. AB - The relationship between social environmental variables and psychological, physical, and speech dysfunction after laryngectomy surgery was examined. The relationships between these categories of dysfunction and the following three social environmental factors were examined: (1) acceptance and emotional support from family and friends; (2) disease-specific support from peers who have had the same surgical intervention and from professionals; and (3) socioeconomic status (SES). Data were collected from 60 total laryngectomy patients an average of 24.3 months after surgery. The type of support provided was different for each source of support, family-friend or peer-professional. Interpersonal support from family and friends was strongly associated with psychosocial and physical dysfunction but had a weaker association with speech adjustment. Diseases-specific support from speech therapists and other laryngectomees was a weaker predictor of dysfunction but a stronger predictor of communication adaptation. SES was not predictive of dysfunction or communication adaptation. Thus different sources of social support can make specific contributions to minimizing physical and psychosocial dysfunction and acquiring skills to overcome the limitations imposed by the surgery. PMID- 2599487 TI - Community housing for chronically mentally ill people. PMID- 2599488 TI - Parkinsonian dysarthria: an aerodynamic and perceptual description of velopharyngeal closure for speech. PMID- 2599489 TI - Clinical application of the high-resolution frequency analyzer. First results. PMID- 2599490 TI - [Audimutitas: An analysis]. AB - There are children who are assumed to have normal hearing and normal intelligence, but who do not speak at all. The phoniatric diagnosis for these children used to be audimutitas. Nowadays these children are not specified any more. They are called language-disturbed and are diagnosed and treated like all other language-disturbed children. An analysis is made of 46 nonspeaking children, aged 1.5-3, who are assumed to understand language in a proper way. The analysis deals with their language (language comprehension, language production and pragmatics) as well as with medical and psychological factors influencing the language disorder. We found no correlations between language comprehension, language production and pragmatics. So, when we know one language aspect, we cannot be sure of the others. We also found various factors contributing to the language problem. PMID- 2599491 TI - [Computed tomography of the larynx in the diagnosis of dysphonia]. AB - By comparing CT scans of the larynx with anatomical sections in the horizontal plane as well as by examining patients, a method of investigation especially aimed at phoniatric questions has been worked out: CT scans are performed every 4 mm parallel to the vocal cord plane using a center of 50 HE and a window of 350 HE. The examination is done during regular respiration and if required can also be performed during phonation when producing the vowel /u/. Using this technique the laryngeal structures of clinical relevance can be demonstrated with the help of at least 10 scans. It requires little time and the radiation exposure for the patient is minimal. The accuracy of CT measurements corresponds excellently to the anatomical features. Allowing an exact evaluation of anomalies of the larynx in shape and position, CT essentially improves phoniatric diagnostics. PMID- 2599493 TI - Airflow, volume, and duration characteristics of sustained vowel productions of normal-speaking children. PMID- 2599492 TI - [Motor speech disorder after removal of a glioblastoma in the left hemisphere: Cortical disorder or apraxia?]. AB - A 38-year-old male patient with a deep central parietal lesion in the left hemisphere reveals a motor speech disorder but no aphasia as evidenced by linguistic testing with the Aachener Aphasietest. Nuclear magnetic resonance tomography of the brain shows no lesion of the brainstem. Whether the speech disorder can be termed cortical dysarthria or apraxia of speech is left open to discussion. PMID- 2599494 TI - [The future of aerosol therapy]. PMID- 2599495 TI - [Arterial hypertension: problems in research and clinical aspects]. PMID- 2599496 TI - [Chronic myeloproliferative diseases. 2: Polycythemia vera rubra]. PMID- 2599497 TI - [Dermatomyositis as a paraneoplastic syndrome. A case report]. AB - A female patient with dermatomyositis with the typical clinical findings of this disease, corresponding histological muscular changes and neurological findings is described. Since in the further course of the disease, recurrent gastric carcinoma was diagnosed, this case again emphasizes the significance of dermatomyositis as a paraneoplastic syndrome, and the need for tumor screening when dermatomyositis is diagnosed in advanced adulthood. PMID- 2599498 TI - [AIDS disease and psychopathology--observations by the psychiatric consultation service of an internal medicine clinic]. AB - The majority of HIV-infected inpatients are treated in departments of internal medicine. For the conditions of the west-german health service it was studied, if and how psychiatric symptoms of HIV-positive inpatients of a University Hospital for internal medicine require a psychiatrist. The evaluation of the suicide risk and psychopharmacological treatment of depressive syndromes were the most frequent reasons to ask for a psychiatrist. It became evident, that by means of a psychiatric consultation service, treatment of psychiatric complications in HIV infection is feasible in a department of internal medicine. PMID- 2599499 TI - [Acute hemorrhage and ischemic necroses in hypophyseal tumors: hypophyseal apoplexy]. AB - Acute enlargement of pituitary adenomas due to haemorrhage or ischaemic necrosis in the tumour was described as "pituitary apoplexy" by Brougham et al. in 1950. Since then, more than 200 cases have been reported, but--especially in the German literature--the syndrome has caught only little attention. Therefore, in a series of 12 own patients, typical findings and clinical characteristics are demonstrated and the literature is discussed. 9 patients had a haemorrhage into the tumour, 3 an acute ischaemic necrosis. The guiding symptom was the acute onset with ophthalmoplegia (11 of 12 patients). Only in one case the adenoma was known before the apoplexy. Other symptoms were headache, blurred vision, drowsiness and, in severe cases, hemiparesis, coma, and hypothalamic disorder. Most important is the acute endocrinological substitution with hydrocortisone; this may be life-saving. Neuroophthalmological recovery depends on early operation: cases of oculomotor palsy require an operation within the first 2 weeks after the acute event. An emergency operation is required only by an acute amaurosis. In general there will be enough time for careful clinical endocrinological and radiological investigations. PMID- 2599500 TI - [Isolated vitamin E deficiency]. AB - Since the detection of vitamin E in 1922, nearly 50 years passed until the recognition that there is a pathogenic vitamin E deficiency in humans. Such a deficiency can be found mostly in a disturbed resorption or transport of the vitamin (mucoviscidosis, chronic cholestasis, abetalipoproteinaemia) and leads typically to a progredient spinocerebellar ataxia in combination with a polyneuropathy. Substitution of the vitamin may hinder a further progression or even lead to an amelioration of the symptoms. Prophylactic treatment in abetalipoproteinaemia prevents the otherwise unavoidable neurological deficits. Isolated vitamin E deficiency is a rare syndrome and the causes are still obscure. We observed a 26 year old male patient with such a isolated vitamin E deficiency who was hitherto thought to suffer from Friedreich's ataxia. The clinical feature showed in addition to the "classical" symptoms of vitamin E deficiency cranial nerve involvement, perioral dystonia and pyramidal signs. Histologically (M. gastrocnemius) we saw the described typical but not specific changes (neurogenic atrophy, phosphatase-positive vacuoles with myelin bodies, cores). An oral vitamin E resorption test yielded a very shortened serum half life. These results support the hypothesis that in the pathophysiology of isolated vitamin E deficiency malelimination plays an important role in addition the known malresorptions models. PMID- 2599501 TI - Take care of ... a charge to the Frontier School of Midwifery and Family Nursing's 99th graduating class. PMID- 2599502 TI - A visit with home health care providers. PMID- 2599503 TI - Complex spermatozoon of the live-bearing half-beak, Hemirhamphodon pogonognathus (Bleeker): ultrastructural description (Euteleostei, Atherinomorpha, Beloniformes). AB - The spermatozoon of Hemirhamphodon pogonognathus shows modifications that are frequent though not obligate in internally fertilizing sperm, notably elongation of the nucleus and extension of the mitochondria of the midpiece as an elongate sheath around the proximal region of the axoneme. These similarities to poecilid and jenynsid sperm are considered homoplasic. As in the mature sperm of all but one investigated teleost, an acrosome is absent. The elongate, blade-shaped, electron-dense nucleus has a mean length of 3.2 microns; its basal implantation fossa, less than one-tenth of the length of the nucleus, houses the anterior half of the distal and only centriole (of triplet construction with satellite rays), a centriolar plug, and a mass connecting the centriole to the wall of the fossa. A unilateral putative centriole adjunct is present. The anterior region of the axoneme is surrounded by a mitochondrial sleeve, and internal to this, separated by a cisterna, by a submitochondrial sleeve. The mitochondrial sleeve unites posteriorly with the submitochondrial sleeve. Between the submitochondrial sleeve and the axoneme is a space, the cytoplasmic canal, that is open to the exterior posteriorly. The discrete, cristate mitochondria, in their sleeve, are unique in investigated atherinomorph sperm in being bilateral, grouped on only two opposing sides of the axoneme, with an arc-shaped "intermitochondrial link" between. The 9 + 2 flagellum is unique for the Animalia in having 23 radial subplasmalemmal rods, repeated longitudinally (periodicity 0.025 microns) in a quasicrystalline array. Internal fertilization is deduced to have arisen in the Exocoetoidei independently of that in the Cyprinidontiformes. PMID- 2599504 TI - Production of bovine tetraploid embryos by electrofusion and their developmental capability in vitro. AB - Optimal conditions of electrofusion for blastomeres of two-cell bovine embryos to produce tetraploid embryos were investigated. The high fusion rate (73-95%), viability, and developmental capacity were obtained under a field strength of 1.0 kV/cm with direct current pulses of 10 or 25 microseconds duration applied twice. Cytological study showed that 78.6% (11/14 embryos) of embryos exposed to electrofusion had tetraploid chromosome sets and the others were diploid or hexaploid. The tetraploid embryos had the capability to develop up to morulae stage in vitro. PMID- 2599505 TI - Parthenogenetic activation of unfertilized mouse oocytes by exposure to 1,2 propanediol is influenced by temperature, oocyte age, and cumulus removal. AB - Cumulus-intact and -denuded unfertilized oocytes from two mouse strains were exposed to 1.5 M ethanol (EtOH) or two cryoprotectant solutions, 1.5 M propanediol (PROH) or 1.5 M dimethylsulfoxide (DMSO), for 4.5 min at 27 degrees C, and the proportion of activating or degenerating oocytes studied. Exposure to DMSO did not significantly increase activation above that of oocytes not exposed to DMSO. Treatment of oocytes in PROH resulted in the activation of up to 87% of viable oocytes. This was significantly higher (P less than .01) than in control oocytes and comparable to the rate of activation after treatment with EtOH (59 96% activation). In solutions at 1 degree C, 47% of control oocytes were activated, which was not significantly different from the rate of activation in EtOH (36%) or PROH (50%) at 1 degree C. Following treatment with PROH, up to 87% of oocytes degenerated within a period of 6 h in vitro. The age of the oocytes (h post hCG) and the time of cumulus removal with the enzyme hyaluronidase, relative to the time of exposure to the chemicals, influenced the level of degeneration in most groups. Significantly fewer oocytes degenerated when cumulus cells were removed before treatment (0-31%) than when the cumulus was left intact throughout the treatment and 6 h culture period (10-87%). Exposure to PROH at 1 degree C reduced oocyte degeneration to 5%. We conclude that PROH causes significantly greater losses of oocytes as a result of parthenogenetic activation and degeneration than of exposure to DMSO. PMID- 2599506 TI - Endpoint of first stage of zona pellucida-induced acrosome reaction in mouse spermatozoa characterized by acrosomal H+ and Ca2+ permeability: population and single cell kinetics. AB - The acrosome reaction induced by the mouse egg's zona pellucida in mouse sperm has been shown to proceed in two stages as characterized empirically by sequential changes in patterns of chlortetracycline fluorescence on the sperm plasma membrane surfaces. The chlortetracycline fluorescence pattern characteristic of fully intact sperm is designated B; in sperm bound to structurally intact zonae that induce the acrosome reaction, the B pattern changes first to an intermediate pattern S and then to a terminal pattern AR characteristic of the completed acrosome reaction. In the same study, it was shown, using a 9-amino acridine fluorescent pH probe, that completion of the first stage was characterized by increase in H+ permeability such that the H+ gradient between sperm head and medium was dissipated. In this study, we show that the fluorescent pH probe 9-N-dodecylamino acridine and the intracellular Ca2+ fluorescent probe fura-2 are both localized to the anterior part of the sperm head encompassing the acrosomal compartment in intact sperm, and the fluorescence associated with each probe is lost as the first stage of the acrosome reaction is completed. Loss of the pH probe fluorescence, pattern N, corresponds to onset of H+ permeability, and loss of fura-2 fluorescence, pattern F, corresponds to onset of Ca2+ permeability. Localization of intracellular fura 2 fluorescence to the acrosomal compartment required extracellular Mn2+ to quench surface-bound fura-2 AM, the tetra-acetoxymethyl ester of fura-2 used to load the cells. Loss of acrosomal fura-2 fluorescence is due to quenching by tracer Mn2+ accompanying Ca2+. Onset of membrane permeability to both H+ and Ca2+, as seen by loss of patterns N and F, occurred in synchrony in populations of sperm bound to isolated, structurally intact zonae, with an overall time course of 210 min postbinding. The loss of pattern N in individual sperm cells bound to zonae was rapid, with a half time of 2.1 min. Concomitant with this rapid loss of pattern N was a shift in the amplitude of flagellar motion from large to small. The lag times to pattern N loss in 50 individual cells ranged from 30 to 140 min. The variable lag times determine the population kinetics; the rate of the endpoint reaction seen in the individual cells is rapid and constant. Dissipation of the H+ gradient with immediate loss of pattern N was readily achieved by addition of nigericin with no change in the time course of the onset of Ca2+ permeability of the membranes enclosing the acrosome.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2599507 TI - Ultrasound-guided transfundal uterine sperm recovery from Macaca fascicularis. AB - Previous studies from this center have indicated that the cynomolgus macaque (Macaca fascicularis) may serve as a model for human sperm interaction with the cervix and uterus. In some macaque species, transcervical aspiration of the uterine contents carries a significant risk of disturbing the cervical milieu due to the serpentine nature of the cervix. The only alternatives have been surgical procedures such as laparotomy or laparoscopy. In this paper, we report our experience with a new technique for ultrasound-guided sampling of spermatozoa in the macaque uterus. Twenty adult female cynomolgus macaques were monitored for menses (first day of menses = day 1), and one mating per cycle was allowed on day 10, 11, or 12. In one group of ten animals, cervical mucus was sampled at 3 or 18 hr postcoitus (pc) and ultrasound-guided uterine aspiration was performed at 24 hours pc. In a second group of ten monkeys, uterine aspiration was at six hr pc and sperm numbers and motility were counted in the uterine fluid. Uterine fluid was obtained from fourteen of twenty monkeys. Pregnancy occurred in ten of the twenty experimental cycles. Ultrasound-guided uterine aspiration appears to be a reliable method for the evaluation of sperm transport in female macaques. The correlations between uterine sperm recovery and cervical mucus sperm populations are discussed. The high conception rate in treatment cycles indicates that this procedure can be performed without apparent risk to pregnancy. PMID- 2599508 TI - Movement of cynomolgus and rhesus monkey spermatozoa collected from the lower female reproductive tract. AB - Postcoital (pc) cervical mucus was collected in 73 menstrual cycles of cynomolgus monkeys and in 43 cycles of rhesus monkeys at 2, 6, 10, 30 hr pc. Videomicrography was used to analyze sperm numbers and movement in the mucus. Both cynomolgus and rhesus monkeys had comparable populations of motile sperm in the mucus at 2 hr pc. However, by 6 hr pc, cervical mucus from cynomolgus monkeys contained twice as many total sperm and motile sperm as mucus from rhesus monkeys (P less than .05). Mean swimming speeds of the free-swimming cervical sperm were similar for the two species at this time. No motile sperm were recovered in mucus from rhesus monkeys at 30 hr pc. In cynomolgus monkeys, however, 14 of the 26 animals examined at 30 hr pc had motile sperm in their mucus. These sperm exhibited lower percent motility, percent free-swimming sperm, and swimming speed than those sperm observed at 6 hr pc. Uterine sperm were collected by transcervical or transuterine aspiration from cynomolgus monkeys. In the transcervical technique, sperm were successfully obtained in four of nine animals examined at 6 hr and in four of five animals at 30 hr pc. The percentage of motile sperm in the uterine fluid was high, 82% +/- 4%, and the swimming speeds (86 +/- 2 microns/sec) were higher than those observed in cervical mucus. Approximately 5-10% of the uterine sperm exhibited swimming motions similar to the hyperactivated motility seen in most mammals. These findings indicate that the sperm cervical mucus interaction in vivo in cynomolgus monkeys has more similarities to the human situation than does the interaction in rhesus monkeys. PMID- 2599509 TI - In vitro maturation and fertilization of domestic cat follicular oocytes. AB - The time course and conditions necessary for oocyte maturation and subsequent fertilization in vitro were studied in the domestic cat. Darkly pigmented oocytes surrounded by cumulus cells and a tight corona radiata were collected from ovaries removed at ovariohysterectomy. After culture in Eagle's minimum essential medium, oocytes were evaluated for nuclear maturation by analyzing chromosomal spreads. Oocytes achieved metaphase II after intervals of 40-48 hr of in vitro incubation. The incidence of maturation was enhanced (P less than 0.05) when oocytes were recovered from inactive (54%) or follicular (56%) stage donors compared to those recovered from luteal phase (29%) or pregnant (35%) cats. The proportion of oocytes successfully maturing in vitro in medium containing no hormone supplementation (37%) was less (P less than 0.01) than counterparts cultured in follicle-stimulating hormone (FSH) only (48%) or FSH and luteinizing hormone (LH) (54%). The efficiency of maturation was not influenced (P greater than 0.05) by either maintenance/transport temperature (4 degrees C vs. 22 degrees C) or delaying recovery of oocytes from antral follicles (2-8 hr vs. 24 32 hr). Approximately 36% of the in vitro matured oocytes cocultured with spermatozoa demonstrated evidence of fertilization; however, there appeared to be a critical development period for maximizing the incidence of fertilization. These results demonstrate that domestic cat antral oocytes are capable of maturing in vitro, and maturation is influenced by the reproductive status of the donor and the presence of gonadotropins in the culture medium. These oocytes are capable of forming embryos and developing to at least the 16-cell stage in vitro. PMID- 2599510 TI - Immunohistochemical demonstration of leucocyte differentiation antigens on paraffin sections using a modified AMeX (ModAMeX) method. AB - The AMeX method (cold Acetone fixation with subsequent Methyl benzoate and Xylene treatment and routine paraffin embedding) has been recently revived for simultaneous preservation of morphology of cells and their antigens. We propose a modification of this method (ModAMeX), with the use of proteolytic enzyme inhibitors and low temperature paraffin wax embedding, which results in better preservation of a large number of leucocyte differentiation antigens and diagnostic morphologic detail. T-cell antigens (CD1, CD2, CD3, CD7 & CD8), B-cell antigens (CD22), macrophage associated antigens (CD11c, CD14 and others), activation antigens (CD25 and others), as well as some other antigens of diagnostic interest (CD10) were found to be preserved with a staining intensity equal to that of sections of fresh frozen tissue. Although the staining intensity of other T-cell antigens (CD4 & CD5), B-cell antigens (CD19, CD21 & CD37), activation antigens (Ki-1) and nuclear proliferation antigen (Ki-67) was slightly weaker as compared with frozen sections, this could be corrected by increasing the monoclonal antibody concentration. Staining for heavy and light chains of immunoglobulins was minor, sometimes compromised due to persistence of background staining as a result of extracellular immunoglobulins. The ModAMeX method has the advantages of simplicity, low cost and the possibility of exchange of tissue material between laboratories. PMID- 2599511 TI - Immunological marker patterns in granulomatous lymph node lesions. AB - The distribution of various types of lymphocytes and macrophages was studied in 19 cases with granulomatous lymph node lesions using 14 monoclonal antibodies. Cases of sarcoidosis, tuberculosis and atypical mycobacteriosis all showed well demarcated granulomas devoid of B-lymphocytes and natural killer cells. In these cases, T-helper: T-suppressor cell ratios were greater than 2 and poor preservation of the normal lymphoid tissue outside the granulomas was seen. In contrast, cases of non-specific lymphadenitis showed less well-demarcated granulomas always containing B-lymphocytes and natural killer cells, with a T helper:T-suppressor cell ratio less than 1 and good preservation of the normal lymphoid tissue outside the granulomas. Immunological marker studies may be helpful in the differential diagnosis of granulomatous lymph node lesions, as well as in the study of the pathogenesis of such lesions. PMID- 2599512 TI - The pathology of cholesterol embolism arising as a complication of intra-aortic catheterization. AB - Cholesterol embolism is an unusual but serious complication of intra-arterial procedures such as arteriography and angioplasty. The pathological findings in four cases confirm that this syndrome is due to disseminated micro-emboli composed mainly of cholesterol crystals and that these originate from atheromatous plaques in the aorta which may be traumatized by the catheter used in the intra-arterial procedure. However, angiography is not the sole precipitating cause of this syndrome but is an exacerbating event in a pre existing process. PMID- 2599513 TI - Mucosal mast cells in reflux gastritis and chronic (type B) gastritis. AB - The histological features that characterize alkaline reflux gastritis are typical of the histamine-mediated response to tissue injury. We have investigated this in nine patients with symptomatic reflux gastritis following partial gastrectomy for duodenal ulcer by determining the gastric mucosal mast cell count before and after Roux-en-Y biliary diversion. Following diversion, the histological picture changed from that of reflux gastritis to type B chronic gastritis in all cases. The mean mucosal mast cell count in all patients was 47.57/mm2 before diversion and 123.33/mm2 after diversion (P less than 0.05). Analysis of the paired data, in which eight out of nine patients showed a rise in mucosal mast cell numbers following bile diversion, also showed a significant difference before and after surgery (P less than 0.01). The gastric mucosal mast cell count is significantly less in reflux gastritis than in type B chronic gastritis. This is most likely to be due to increased degranulation, which would explain why striking vascular changes occur in the absence of inflammatory cell infiltration in reflux gastritis. PMID- 2599514 TI - Coronary artery aneurysm due to primary cardiac lymphoma. PMID- 2599515 TI - Giant hepatic angiomyolipoma. PMID- 2599516 TI - Spindle cell haemangioendothelioma in association with epithelioid haemangioendothelioma. PMID- 2599517 TI - Blood-borne metastases from an immature teratoma of the ovary in a 36-year-old woman. PMID- 2599518 TI - A grand alliance takes shape behind 'Facts for Life'. AB - Convinced that if parents could be reached with today's health knowledge and supported in putting it into use, child survival and development would experience a great forward surge, WHO, Unicef and Unesco have compiled a ten chapter summary of the essential information parents need. This booklet is Facts for Life, but more than a publication, it is a movement and the handbook of a grand alliance of communicators. PMID- 2599519 TI - The facts on the Facts for Life in Turkey. PMID- 2599520 TI - Sri Lanka's religious leaders back Facts for Life. PMID- 2599521 TI - Facts for Life in the Philippines. PMID- 2599522 TI - Behavioural change strategies to enhance child survival. AB - The evolution of different approaches to health education and additions from educational psychology have brought some guidelines for influencing new health behaviours. The purpose of this article is to take stock of some of the achievements, strengths and limitations within the field of communication and education and to delineate some behavioural science principles and theoretical models that could guide the health educators in child survival efforts. PMID- 2599523 TI - Rapid assessment procedures are changing the way UNICEF evaluates its projects. AB - The Rapid Assessment Procedure establishes a link between information and decision-making by focusing on why and how problems occur. PMID- 2599524 TI - In rural Indonesia social marketing of oral rehydration salts the mothers' perspective. AB - The Indonesia Health Department has been intensifying efforts to increase mothers' access to and use of oral rehydration salts (ORS) for the last several years. The approach utilizes a social marketing perspective to persuade the parents. This report describes the results of two consecutive field interventions using this approach. The first utilized a combination of public sector and commercial sector resources. The second used the public sector alone. PMID- 2599525 TI - Passage to child survival. PMID- 2599526 TI - Mobilizing youth to implement health policy case study: Colombia. AB - Colombia, South America's fourth largest country in area and third in population has been embarked since the late 1970s on a national programme reflecting the promotion of a highly positive health policy, an integral part of the national commitment to "change with equity". A key element of the policy's development, promotion and implementation has been the mobilization of youth, and through them their parents, as active educators and promoters of better health. The central thrust has been the empowerment of families to provide self-care and make more efficient use of the health services available to them. PMID- 2599527 TI - In Tanzania: The Iringa Nutrition Programme. AB - Recognition that malnutrition can be rooted in the social system was a key to success for the Iringa's Nutrition Programme (INP) assisted by Unicef and WHO. And this perception was in turn made possible by the development of a conceptual framework and problem-solving methodologies that promise to be valuable in other countries. PMID- 2599528 TI - The dentist's responsibility in identifying and reporting child abuse. PMID- 2599529 TI - Politics of AIDS. PMID- 2599530 TI - Tooth apex welding using the CO2 laser. PMID- 2599531 TI - The team approach to treating cleft lip/palate and other craniofacial anomalies in Illinois. PMID- 2599532 TI - The dentist's role in identifying and reporting child abuse. Part II. PMID- 2599533 TI - Mitral valve prolapse syndrome. PMID- 2599534 TI - Coronary arteriographic findings soon after non Q wave myocardial infarction. AB - We performed early coronary arteriography in 27 patients (23 males, 4 females) having non Q wave MI. Infarct related vessel (IRV) was totally blocked in 25.9%, whereas 66.7% had severe residual stenosis (greater than or equal to 70%). Left main was involved in 7.5%, and at least 2 major coronary arteries were involved in 51.8%. Visible collaterals were seen in 11%. We feel, as compared to transmural MI, where total occlusion of IRV is common, the higher incidence of subtotal occlusion of IRV with severe residual stenosis, poor collaterals and significant involvement of at least one other major coronary artery may be responsible for observation of early recurrent ischemic episodes in non Q wave MI. PMID- 2599535 TI - Prevalence and clinical significance of coronary artery ectasia (an angiographic study). AB - Coronary cine-angiograms of 1,042 patients were reviewed for the presence of ectasia of major coronary arteries. Ectasia or irregular dilatation of the coronary artery was defined as 1.5 times diffuse or segmental dilatation as compared to segment of normal caliber coronary artery. Forty-one (3.9%) patients were found to have diffuse or localised coronary artery dilatations with segments of normal caliber throughout the length of major vessels. Mean age of the patients was 52 years, and majority were males (39, 95%). Right coronary artery (RCA) and left circumflex (Cx) were involved in 23 (56%) each, left anterior descending (LAD) in 15 (37%), obtuse marginal in 4 (10%) and left main in 2 (5%). Multiple vessel involvement was present in 21 (51%). Evidence of myocardial infarction was present in 21 (51%). Major risk factors were not different from the patients with coronary artery disease without ectasia. PMID- 2599536 TI - Prognostic significance of risk factors in acute myocardial infarction in young. AB - The study included 45 consecutive patients in the age group of 27 to 39 years presenting with AMI diagnosed by typical history, ECG changes and enzyme response. Prognostic significance of various risk factors in AMI in young was evaluated. There were 41 M (91.1%) and 4 F (8.9%) with mean age of 34.6 years. ECG showed anterior myocardial infarction (MI) in 18 (40%), inferior MI in 15(33.3%), Subendocardial inf in 10(22.5%) and combined anterior and inferior MI in 2 (4.5%) cases. Various risk factors were: Smoking (60%), hyperlipidemia (44.4%), stress (40%), hypertension (28.9%), family history (28.9%), diabetes mellitus (15.7%) and obesity (8.8%). Attention was given on atherogenic index (AI) (22.2%). Coronary angiogram was done in 20, which revealed significant coronary arterial obstruction in 15 cases; 3-vessel disease (n = 7), 2 vessel disease (n = 4) and single vessel disease (n = 4). Both 3 VD and 2 VD were associated with high AI. Risk factors (RF) were grouped as RFGI when combination of 3 or more RF were present, and RFG II when 2 or less RF were present. RFGI and RFGII were present in 40% and 60% cases respectively. Prognostically, patients were divided in two groups of MI-fatal (6) and nonfatal (39), the latter were subdivided into complicated (14) and uncomplicated (25). It was observed that more fatal cases were found in RFGI, whereas nonfatal uncomplicated MI was more in RFG II (P less than .001). PMID- 2599537 TI - A cross-over trial comparing the effects of acebutolol and propranolol on the serum lipids and hypertension. AB - A two-way cross-over trial comparing the effects of acebutolol and propranolol on the lipid profile was conducted. 50 patients were evaluated. The primary objective was to determine whether treatment by certain classes of beta-blockers induced deleterious effects on the serum lipids which could partially or wholly negate the beneficial effect of controlling hypertension. Each patient served as his/her own control, and received 6 weeks of therapy with acebutolol and 6 weeks of therapy with propranolol. The analysis of the results revealed that acebutolol did not have any adverse effect on the lipid profile in contrast to reports which implicate other beta-blockers in inducing pro-atherogenic changes in the serum lipid profile; but acebutolol and propranolol were equi-effective in controlling hypertension. PMID- 2599538 TI - Myocardial bridge (MB): an angiographic curiosity? AB - The coronary angiograms of 1,500 cases performed between 1981 and 1989 were analysed to find out the incidence of Myocardial Bridge (MB) and its significance as regards myocardial ischemia. Sixteen of these (1.06%) were found to have MB. Their ages ranged from 27-70 years (m = 49.2) and male:female ratio was 13:3. Out of 16 patients, 7 (group A) had associated coronary artery disease (CAD) (7 of 1421; 0.49%) and remaining 9 (group B) had no associated CAD (9 of 79; 11.39%). All the MB were found on left anterior descending artery (LAD) (3 on proximal LAD and 13 on mid LAD). No MB was found on right coronary artery (RCA) or circumflex arteries. The location of the MB did not affect the pattern of CAD. Chronic stable angina was the commonest presenting symptom in group A patients (5 out of 7) and atypical angina in group B patients (5 out of 9). Majority of group B patients had either normal or nonspecific ST-T changes in ECG (7 out of 9). However, the presence of previous myocardial infarction or ECG evidence of 'Q' wave infarction (2 out of 2) was always associated with significant CAD. Similarly, regional wall motion abnormalities on echocardiogram were always found in patients with significant CAD and old myocardial infarction. All 9 patients with MB and normal coronary arteries were managed conservatively with good relief of symptoms, whereas other seven patients were managed on the merits of the underlying CAD. In conclusion, the MB is a normal variant found incidentally on coronary angiography, and does not have any definite clinical correlations or pathological significance. PMID- 2599539 TI - Single ventricle (morphologic study of 21 cases). AB - The morphological characters of 21 cases of single ventricle which constituted 1.63% of cases of congenital heart disease were studied. The single ventricular chamber with left ventricular characters was seen in 11 cases. In 8 of these, the great vessels were transposed with aorta arising from outlet chamber (SLL-7:SDD 1). Except in one case where there was common A-V valve, two A-V valve, two A-V valves entered the main chamber with some abnormality of A-V valves in all the cases. Bulbo-ventricular foramen was obstructive in 6 cases with resultant hypoplasia of aorta. Aortic arch anomalies were present in 5 of these. Valvular pulmonary stenosis was present in two. In 3 cases with normally related great vessels (SDS), bulbo-ventricular foramen was obstructive in two with hypoplastic pulmonary artery. Abnormalities of A-V valves were similar to the previous group. The incidence of single right ventricle was high in this series (47%). In half the cases, there was associated asplenia syndrome. This group in general showed common atrium with exception of one case, common A-V canal, both great vessels arising from same outflow with atrophic conal septum. Anomalies of pulmonary veins were common. The subsets observed were ADD-3, ADL-1, AL single trunk-1. In the remaining cases without asplenia, both A-V valves were present though some abnormalities were present in all. Systemic and pulmonary venous anomalies were rare. The subsets observed were SLL-3, SDL-1, SDD-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2599540 TI - Catecholamine-induced experimental cardiomyopathy--a histopathological, histochemical and ultrastructural study. AB - An experimental model of myocardiopathy was induced in rhesus monkeys following noradrenaline (NA) infusion (20 ug/kg body wt/minute), for a period of 2 hours daily for three consecutive days. The animals were sacrificed after two hours (acute phase), forty-eight hours (sub-acute phase) and twenty-one days (chronic phase). Focal depletion of succinic dehydrogenase, increase in adenosine triphosphatase, acid phosphatase and appearance of large fat droplets in myocardial muscle was noted in the acute phase. Histopathological examination revealed focal edema, opacity and fuchsinorrhagia of the muscle fibres distributed in both the ventricles. Myofibrillar degeneration, myocytolysis and vacuolization with aggregation of lymphomononuclear cells were the significant features in the acute phase. During sub-acute and chronic phases, these features became less prominent and reparative changes with proliferation of fibroblasts became more marked. By the twenty-first day, irregular, focal scars replaced the necrosed myocardium. Ultrastructurally, heart muscle showed myofibrillar disorganisation, distortion of Z and A bands, dilatation of sarcoplasmic reticulum and swelling and rupture of mitochondria. Altered membrane permeability was evidenced by the presence of reaction products of horseradish peroxidase within the cardiac cells. In the reparative phase, however, myocytolytic changes regressed and collagen deposition was the prominent feature. This experimental study has several histological features simulating human cases of myocardial infarction without coronary occlusion. PMID- 2599541 TI - Follow-up of balloon aortic valvuloplasty in young adults--a combined hemodynamic and Doppler echocardiographic study. AB - Percutaneous Balloon Valvuloplasty was performed in 25 patients with severe aortic stenosis (Aortic valve area index: 0.23 to 0.70, mean 0.36 +/- 0.11 cm2/m2). The mean age was 23 +/- 15 (range 6-66) years, and majority (n = 18) had noncalcific valves. Valve morphology was bicuspid in 14, tricuspid in 6 and indeterminate in 5. Valvuloplasty resulted in a fall of peak systolic gradient (PSG) from 112 +/- 35 to 34 +/- 16 mmHg (p less than 0.001), and an increase in aortic valve area (index) (AVAI) from 0.36 +/- 0.11 to 0.82 +/- 0.43 cm2/m2 (p less than 0.001). Follow-up data at 16 +/- 6 months were available for 18 patients, 80 per cent of whom registered symptomatic improvement. Repeat catheterization, performed in 12 cases, showed increase of PSG to 53 +/- 22 mmHg and a fall in AVA (1) to 0.62 +/- 0.24 cm2/m2, as compared to the results immediately following the procedure. In addition, 3 patients had their valve areas estimated by doppler echocardiography. Forty-six per cent of these 15 patients (n = 7) showed evidence of restenosis. Four out of these 7 cases had calcific valves, whereas none of the patients who had sustained improvement had calcification. Tricuspid morphology was present in 50 per cent of the group with sustained improvement, as compared to 20 per cent of the group that restenosed. Our preliminary data shows sustained hemodynamic improvement after balloon dilatation in young patients with severe aortic stenosis with noncalcific and tricuspid aortic valve. PMID- 2599542 TI - A study of lung function and oxygen uptake during exercises in cases undergoing mitral valve surgery. AB - In 1986-7, 80 cases with isolated mitral valve disease undergoing open heart surgery were studied, for spirometry, resting and exercise, oxygen uptake (VO2) preoperatively and 3 months postoperatively. Pulmonary artery pressures (PAP) were recorded prior to surgical correction and soon afterward. Pulmonary hypertension was mild (I) in 56.2%, moderate (II) in 25% and severe (III) in 18.8% cases. Though spirometric functions were lower with severe PH, these did not improve significantly 3 months later. But direct MBC improved significantly in grs. I and II, along with exercise VO2 and mean PAP. (DMBC:75.7 lit. to 91.8 lit: P less than 0.001; Exercise VO2 798 ml to 983 ml: P less than 0.001). Mean PAP 56.8 to 39.5 mm: P less than 0.001). Thus these functions may be used to objectively evaluate physiologic changes in cardiac surgical cases. PMID- 2599543 TI - Efficacy of pre-operative levo-phase pulmonary angiograms in detecting left atrial thrombi. AB - We have studied the efficacy of levo-phase pulmonary angiograms in detecting thrombosis of the left atrium or its appendage in 33 patients with rheumatic mitral stenosis who subsequently underwent open-heart surgery. Left atrial thrombi had been suspected in all these patients due to the presence of atrial fibrillation and/or history of systemic embolization. The angiographic criteria for the presence of thrombus included mobile or persistent fixed filling defects of constant size in the contrast shadow of the left atrium or its appendage, partial or complete non-visualization of the left atrial appendage, irregular outline of the left atrium or its appendage and an atrial chamber which appeared smaller than the atrial shadow. 19 patients showed one or more angiographic features of thrombosis. All the patients subsequently underwent open-heart surgery for mitral valve disease, and thrombi were found in 17 patients. The angiogram was false positive in three patients, and false negative in one patient. The angiographic diagnosis of left atrial thrombosis by levo-phase pulmonary angiography has a sensitivity of 94%, specificity of 81.3%, and predictive value of 84.2%. Non-visualization of left atrial appendage as the only feature of thrombus formation was seen in five patients, and thrombi were subsequently formed at surgery in four patients (80%). Levo-phase pulmonary angiograms are safe and reasonably accurate for preoperatively detection of left atrial thrombi, and should be performed in all the patients of mitral stenosis if left atrial thrombi are clinically suspected. PMID- 2599544 TI - Prostaglandin E1 (PGE1): effect on the human fibrinolytic system. AB - The in vitro effect of prostaglandin E1 on the fibrinolytic process was assessed in 30 patients with acute myocardial infarction (MI) using Thrombin Time (TT) and Euglobulin Clot Lysis time (ECLT) as parameters. Thrombin time was shortened and ECLT was prolonged (p less than 0.001) in acute MI as compared to thirty age and sex matched controls. In both groups, preincubation of sera with PGE1 (3.3 micrograms/ml) produced prolongation of TT and shortening of ECLT (p less than 0.001). Thus PGE1, which is a naturally occurring vasodilator and antiplatelet agent, also appears to have fibrinolytic activity. PMID- 2599545 TI - Congenital aneurysms of the sinus of Valsalva with dissection into the interventricular septum. AB - Four cases of congenital aneurysm of sinus of Valsalva (CASV) with rupture and dissection into the intraventricular septum are described. Their incidence (26.6%) in 15 consecutive cases of CASV is unusually high. Only one of these showed secondary rupture into the left ventricle. If these aneurysms remain unruptured, their diagnosis during life is difficult as in the case of other unruptured aneurysms of CASV. The occurrence of conduction abnormalities in young patients should be one of the indications, and 2-D echocardiography would help to arrive at a definite diagnosis and aid in the institution of appropriate surgical treatment. PMID- 2599546 TI - Complete A-V block and phrenic paralysis complicating surgical closure of ventricular septal defect--a case report. AB - The incidence of post-surgical complete A-V block has come down from 16% in the 50's to less than 1% with improvement in technique. Of these, 14% are transient and attributable to post-operative oedema and haemorrhage at the site of block. Permanent damage manifests early, or as late as 15 years, and in these, the risk of sudden death is a reality. Phrenic paralysis has been attributed to inadvertent pinching, cutting, traction on the phrenic nerve, and has been noticed after pericardiectomy, Blalock-Hanlon operation, Mustard repair, performance of a Blalock-Taussig shunt or closure of ASD. It has also been noted to result from hypothermic injury following iced saline slush application for topical hypothermia the so called "Frost Bitten Phrenics". The entity is commoner than appreciated, although its actual incidence has not been properly worked out. It can be unilateral or bilateral. Patients are mostly asymptomatic, the post operative X-Ray chest revealing the defect. Uninhibited movement of the costal margin away from the midline on the side of paralysis gives clinical clue (Hoover's Sign), and is confirmed by fluoroscopy which shows paradoxic diaphragmatic movement on sudden sniffing (Keinbock's Phenomenon). PMID- 2599547 TI - Massive congenital submitral aneurysm of the left ventricle: a case report. AB - Subannular left ventricular aneurysm adjacent to the mitral valve is a rare entity predominantly seen in the young blacks. A young Indian patient with massive submitral left ventricular aneurysm (10.6 cm x 7.5 cm) presenting with congestive heart failure is reported with 2D-echocardiographic, haemodynamic and cineangiographic and pathologic data. PMID- 2599549 TI - Tricuspid valve replacement for gross tricuspid insufficiency due to dysplastic valve--a case report. AB - A case report is presented of a child in whom there was gross tricuspid insufficiency due to marked dysplasia of the tricuspid valve. This patient received prosthetic valve replacement in tricuspid position with excellent post operative improvement. To the best of our knowledge, this is the first case report of a tricuspid valve replacement for a severely dysplastic tricuspid valve. PMID- 2599548 TI - Cardiac amyloidosis--a case report. AB - A 75-year-old male patient presented with resistant congestive cardiac failure. Echocardiographic examination revealed normal left ventricular size with symmetrical hypertrophy and generalised hypokinesia. In addition, there was a characteristic granular sparkling appearance of the myocardium. Cardiac catheterization showed biventricular diastolic restriction with normal coronary arteries. Possibility of cardiac amyloid was considered, and the diagnosis was confirmed on rectal biopsy. PMID- 2599550 TI - Effect of thyroid hormones on delayed type hypersensitivity reaction. AB - The effect of long term administration of thyroid hormones and its deprivation on delayed type hypersensitivity (DTH) reaction to 2-4 dinitrochlorobenzene (DNCB) was studied. Animals were either pre-treated with thyroid hormones (T3 or T4) for 15 days and then subjected to DNCB skin test or the animals received thyroid hormones and simultaneously subjected to DNCB skin test. In both the cases DTH reaction was found to be increased significantly. When DNCB skin test was performed in the thyroidectomized animals, DNCB skin reaction was significantly decreased and the reaction was restored to normal following supplementation of thyroid hormones to the thyroidectomized animals. TLC and ALC were increased significantly following hormone treatment and thyroidectomized animals. TLC hand, induced significant depression in the count which was restored by hormone administration to the thyroidectomized animals. PMID- 2599551 TI - Is there any delta 5-3 beta hydroxysteroid dehydrogenase activity in preimplantation embryo of rhesus monkey? AB - This is the first report on the histochemical assessment of delta 5-3 beta hydroxysteroid dehydrogenase activity in all the preimplantation embryonic stages in the rhesus monkey (Macaca mulatta). An apparent stage dependent increase in enzyme activity was obtained, however, distinctively a high degree of non specificity in enzyme reaction was noted primarily in morulae and blastocysts. Such marked non-specificity in the histochemical enzyme reaction for delta 5-3 beta hydroxysteroid dehydrogenase activity was not found in mouse blastocysts. High amounts of endogenous steroids present within rhesus embryos, or the participation of non-specific dehydrogenases could account for the observed non specificity. Furthermore, the present report documents the pattern and degree of association (r = 0.9; P less than 0.01) between developmental stage and gestational age of preimplantation rhesus embryos, and thus provides a normal in situ cell cleavage rate of preimplantation embryo in the rhesus monkey. PMID- 2599552 TI - Antigonadotropic activity of pineal gland of the Indian palm squirrel Funambulus pennanti. AB - Bioassay of the pineal extract of F. pennanti was performed in immature female mice which was previously sensitized with human chorionic gonadotrophin. Reduction of ovarian and uterine weights indicated an antigonadotropic nature of the pineal gland of this animal. PMID- 2599553 TI - Influence of exogenous thymidine on killing and mutation of Chinese hamster V-79 cells by X-rays, ultraviolet light and N-methyl-N'-nitro-N-nitrosoguanidine. AB - V-79 cells when exposed to thymidine (5 micrograms/ml) in growth medium after treatment with X-rays, UV light and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), responded differently depending upon the agent. For treatment with X-rays and UV light, only induction of mutation was potentiated, but for MNNG treatment, both killing and mutation induction were potentiated. The increase in killing of MNNG exposed cells could be reversed by simultaneous addition of deoxycytidine with thymidine, but, for all the three mutagenic treatments, enhancement in mutation induction could not be suppressed by deoxycytidine. PMID- 2599554 TI - Induction of lipid peroxidation in calcium oxalate stone formation. AB - The function of lipid peroxidation and the anti-peroxidative enzymes of rat liver and kidney were investigated under hyperoxaluric and stone forming conditions. The experimental animals showed higher malondialdehyde content in liver and kidney than that of control. A significant increase in malondialdehyde release was observed in the experimental liver or kidney when incubated with either ferrous sulphate or hydrogen peroxide compared to that of control liver or kidney. Superoxide dismutase activity was not affected in the hyperoxaluric rats while there was a moderate increase in the stone forming rats when compared to control. Highly significant decrease in catalase activity was observed in both conditions in liver and kidney compared to control. PMID- 2599555 TI - Methyl 5(6)-(alpha-hydroxyphenyl methyl) benzimidazole-2-carbamate and cysticercosis: chemotherapeutic and electron microscopic studies. AB - Methyl 5(6)-(alpha-hydroxyphenyl methyl) benzimidazole-2-carbamate, a major metabolite of mebendazole was evaluated against Cysticercus fasciolaria (larval form of Taenia taeniaeformis) in rats. The metabolite was assessed in various doses. A regimen of 50 mg/kg x 10 (ip), given one day apart, was found to be most effective and killed all the mature cysticerci. On developing cysts, the treatment was initiated in two schedules; 5 days prior to (d-5 to d-1) and 5 days after (d + 6 to d + 10) administration of T. taeniaeformis eggs to rats. The later protocol with 100 mg/kg x 5 dose (ip) resulted in 95% inhibition in the establishment of cysticerci. Activity of mebendazole against mature cysts was parallel to metabolite whereas against developing cysts, it was inferior. The time related topographical changes that occurred in mature C. fasciolaris after treatment with metabolite (50 mg/kg x 10, ip, one day apart) were observed by scanning electron microscopy. There was loss of contractivity, gradual disappearance of microtriches and progressive degeneration of tegument. Similar changes were noticed with mebendazole. The possession of better efficacy and higher safety range [Indian J Exp. Biol, 25 (1987) 871], suggests that the metabolite can be a potential anthelmintic for man and animals. PMID- 2599556 TI - Studies on in vitro synthesis of serum lipoproteins in rats maintained on normal and atherogenic diets: effects of cobalt and manganese supplements at deficient and abundant doses. AB - The effects of Co(II) and Mn (II) supplements at abundant as well as, deficient doses on in vitro synthesis of serum lipoproteins in rats maintained on normal and atherogenic diets were studied. While an adequate oral supplement of Co(II) or iv administration of Mn (II) at very low doses to the experimental rats fed on salt-free stock ration diet produces hyperlipidemic changes in increasing C/P ratio in serum and also the serum LP content. On the other hand, the animals on atherogenic diet supplemented with deficient Co(II) or excess Mn(II) results in a lowering of hyperlipidemia and hyperlipoproteinemia, with concomitant decrease in C/P ratio. Dietary lipids (eg. cholesterol, butter-fat etc.) vis-a-vis Mn (II) deficiency or Co(II) in excess reflect a homeostatic control mechanism for keeping the excess lipid in a state of solution as lipoprotein complexes. Deficient Co(II) or excess Mn (II) in turn, results in a decrease in protein synthesis and a relatively impaired rate of secretion of protein from liver to serum. Moreover, Mn (II) deficiency increases, while its abundance, significantly restricts 14C- labelled amino acid incorporation into alpha 2-lipoprotein molecules. Neither cobalt depletion, nor its adequate oral substitution help improvise the hepatic synthesis of alpha 2-apolipoproteins in experimental animals. This situation remains unaltered even by overloading the diets with saturated fats or by other atherogenic agents, instead of vegetable oils preferably rich in mono or dienoic fatty acids. PMID- 2599557 TI - Effect of dietary zinc and copper on peripheral blood plasma cholesterol, testosterone and histomorphology of testes in rats. AB - Total plasma cholesterol (mg/dl) significantly (P less than 0.01) decreased from 70.8 to 54.01 as the dietary Cu levels increased from 2.5 to 5 ppm at 12 pm Zn concentrations in male weanling rats. A similar trend was observed in the blood peripheral testosterone concentration at 12 ppm Zn and 2.5 ppm Cu. Histological examination of testes revealed smaller seminiferous tubules with atrophy of germinal epithelium. Also a marked loss of spermatogenic cells was observed in Zn and Cu deficient rats. PMID- 2599558 TI - Glutathione as an inhibitor of trypsin induced proteolysis. AB - Glutathione has been shown to inhibit trypsin induced proteolytic activity. A concentration of 6 mM of glutathione was found to completely inhibit proteolysis of 3H-proline labelled underhydroxylated procollagen as a substrate, whereas a concentration of 2.1 mM of glutathione caused 50% inhibition of proteolysis. When azocoll was used as a substrate for trypsin 50% inhibition of proteolysis was achieved with 1.4 mM of glutathione, though a complete proteolytic inhibition was attained at 4 mM glutathione. The results suggest that glutathione may be playing an important role in protein metabolism in a variety of disease and stress states. PMID- 2599559 TI - Survival of mouse embryos after being frozen in glycerol-sucrose mixture. AB - Random bred female albino mice (6-8 weeks old) were used as a source of embryos. 8- to 16 cell embryos were dehydrated in glycerol-sucrose mixture in 0.25 ml straws at room temperature. Straws were cooled at the rate of 5 degrees C/min to 7 degrees C. Seeding was induced by touching the out side of the straw at -7 degrees C. Straws were further cooled at 0.5 degree C/min down to -35 degrees C and then plunged into liquid N2. Thawing of straws was done by direct transfer into water at 35 degrees C. Frozen-thawed embryos were cultured in a CO2 incubator maintained at 39 degrees C. Out 190 embryos (8-16 cell) initially frozen, 169 (88.94%) were recovered on thawing. 158 (93.5%) out of 169 were apparently normal and used for culture. 75 (47.46%) developed to morulae/early blastocysts and 72 (45.56%) to expanded blastocysts on 24 and 48 hr culture respectively. In conclusion, the incorporation of sucrose in the freezing medium at a concentration of 0.25 M has led us to propose a freezing, thawing and transfer method without dilution of glycerol. The technique being quite simple is worth trying in farm animals where importance of this technique in non-surgical transfer of frozen-thawed embryos will be a boon. PMID- 2599560 TI - Hematological effects of textile mill effluent on freshwater fish Oreochromis mossambicus (Trewaves). AB - O. mossambicus was exposed to sublethal concentrations of a textile mill effluent to study the hematological changes as a function of feeding/starvation, aeration/non-aeration and concentration. Increase in concentration produced a dose dependent increase in RBCs (0.87 x 10(6) to 1.63 x 10(6)/mm3), WBCs (0.070 x 10(6) to 0.520 x 10(6)/mm3), hemoglobin (3.7 to 5.6%) and hematocrit (9.0 to 12.3%) and a decrease in MCV (111.8 to 88.2 microns 3), MCHC (41.05 to 31.35%) and MCH (44.2 to 33.9 pg). PMID- 2599561 TI - Improvement of long term survival in portal hypertension: a dream yet to come true. PMID- 2599562 TI - Prognostic markers in upper gastrointestinal hemorrhage. AB - This study was undertaken to ascertain whether clinical and endoscopic factors can predict the outcome in patients with acute upper gastrointestinal hemorrhage. A total of 185 patients admitted with hematemesis over a 4-year period were studied. Clinical evidence of shock and hepatocellular dysfunction and hemoglobin level were noted on admission. Endoscopy was performed within 48 hours of admission to look for the site and number of lesions, and stigmata of hemorrhage. On analysis, age, clinical evidence of shock, hepatic dysfunction and hemoglobin less than 8.0 g/dl (80 g/L) were found to be significant in prediction of risk of further hemorrhage. Similarly age, past history of jaundice, previous bleeding episodes and clinical evidence of hepatic dysfunction were statistically significant predictors of mortality. Bleeding from varices and peptic ulcer was associated with a worse prognosis than acute mucosal lesions. It is concluded that clinical and endoscopic factors can be used to identify a group of patients at high risk of further hemorrhage and mortality. PMID- 2599563 TI - Prognostic value of rectal biopsies in idiopathic ulcerative colitis. AB - Eighty seven biopsies and five total colectomy specimens following surgery were studied in 40 cases with idiopathic ulcerative colitis. They were categorised as acute ulcerative colitis with evidence of chronic activity in the first or subsequent biopsies (10 cases), chronic active ulcerative colitis (25 cases), and chronic quiescent ulcerative colitis (5 cases). The histological criteria were predefined with special reference to chronic crypt changes. Repeat biopsies were available in 28 cases and were found to be valuable in diagnosis and follow up of the disease. PMID- 2599564 TI - Endoscopic sphincterotomy--experience with 110 patients. AB - During the last two years, 116 endoscopic sphincterotomies (ES) were attempted in 110 patients. The indication for ES was choledocholithiasis in 102 (93%) patients, including 37 (36.2%) with gallbladder in situ and 65 (64%) post cholecystectomy patients; the other 8 (7%) were performed for stricture of the lower end of the common bile duct (CBD) with cholangitis (2), insertion of nasobiliary drain (2), restenosis after previous sphincterotomy (1), stone in the cystic duct stump causing cholangitis (1), papillary stenosis (1) and post cholecystectomy cholangitis with no obvious cause (1). ES was achieved in 113 (97.4%) attempts in 107 (97%) patients and was overall successful in 81% of patients. Of the 95 patients with choledocholithiasis in whom ES could be performed and a follow-up was available, 79 (83%) cleared their CBD. Of 98 patients with choledocholithiasis, 79 (80.6%) finally cleared their CBD of stones. Three patients developed complications, one needing emergency operation. There were no deaths. ES was found to be effective in patients with retained stones and also in patients with choledocholithiasis with gallbladder in situ, especially those who were poor surgical risk. PMID- 2599566 TI - Gallbladder preservation in stone disease. PMID- 2599565 TI - Evaluation of endoscopic variceal sclerotherapy in various grades of liver disease. AB - Forty four patients with portal hypertension of varying etiology, including 25 patients with an acute episode of variceal bleeding and 19 with past history of hematemesis, were followed up for eighteen months following endoscopic variceal sclerotherapy (EVS). Of 11 patients in Child's A group, two died of acute bleed, three were subjected to shunt surgery and the remaining six survived the follow up period. Ten of 11 cases in Child's C did not survive more than six months in spite of sclerotherapy. We conclude that rebleed and death due to rebleed following EVS occur more commonly in patients with poor hepatic reserve (Child's C) as compared to patients in Child's A and B. PMID- 2599567 TI - Choledocho-duodenal fistula due to tuberculosis. AB - An unusual case of caseating nodal tuberculosis causing a choledocho-duodenal fistula is reported. Anti-tubercular treatment led to closure of the fistula. PMID- 2599568 TI - Collision tumour of stomach. AB - Collision tumour of the stomach is exceedingly rare, with only four previous reported instances in which adenocarcinoma of the stomach was found in association with a single carcinoid tumour. Our case with adenocarcinoma had multiple carcinoid tumours in the stomach. PMID- 2599569 TI - Primary adenocarcinoma of duodenum. PMID- 2599570 TI - Ileocecocolic intussusception produced by lymphoblastic lymphoma of ileum. PMID- 2599571 TI - Trichobezoar: a rare cause of gastric perforation. PMID- 2599572 TI - Villous adenoma of duodenum. PMID- 2599573 TI - Malacoplakia of the appendix. PMID- 2599574 TI - Ascarial abscess of omentum. PMID- 2599575 TI - Diarrhea in medullary carcinoma of thyroid. PMID- 2599576 TI - Association of Candida with carcinoma of esophagus. PMID- 2599577 TI - Effects of pretreatment sterilization and cleaning methods on materials properties and osseoinductivity of a threaded implant. AB - A new endosseous titanium implant has been designed to replace skin adhesives as a method of retention of maxillofacial prostheses. The effects of various methods of preimplantation preparation on surface characteristics of the implant were analyzed with electron spectroscopy for chemical analysis. Having undergone one of several pretreatment protocols, fixtures were implanted in the crania of Yucatan miniature hairless swine. Both argon radiofrequency glow discharge and ultraviolet chamber treated implants were associated with the rapid ingrowth and maturation of new bone around the fixture. Conventional steam sterilization was associated with a paucity of neo-osteogenesis accompanied by the production of thick collagen slings at the interface. Apparently, the bulk material, fixture design, and method of surface preparation all contribute to the ultimate clinical fate of an implant. PMID- 2599578 TI - Generation of new bone around titanium implants using a membrane technique: an experimental study in rabbits. AB - Insufficient bone volume may be a significant problem in connection with dental implants. In this study, a technique based on the principle of guided tissue regeneration was tested for its ability to generate bone tissue around titanium implants. Implants were inserted in tibiae of rabbits. To create a secluded space for osteogenesis and to prevent soft-tissue ingrowth, a porous Teflon membrane was placed around exposed parts of the implant. Where a membrane had been used, the threads of the implant were completely covered with significant amounts of new bone. This study indicates that the membrane technique is a reconstructive surgical method that may be applicable to create new bone around exposed parts of titanium implants in a clinical setting. PMID- 2599579 TI - A study of in vitro attachment of Streptococcus sanguis and Actinomyces viscosus to saliva-treated titanium. AB - This study examined the initial attachment of Streptococcus sanguis G9-B and Actinomyces viscosus T14V to saliva-treated powdered enamel and titanium surfaces. Using an in vitro adherence model, significantly lower numbers of Actinomyces viscosus T14V bound to the saliva-treated titanium surface when compared to that of the similarly treated enamel. The binding of Streptococcus sanguis G9-B to titanium or enamel did not vary significantly. A comparison of the percentage of cells bound to the titanium surface revealed that S sanguis cells attached in significantly higher numbers when compared to the A viscosus cells. PMID- 2599580 TI - Ridge mapping for determination of alveolar ridge width. AB - Ridge mapping is a measurement procedure to ensure that the diameter of an endosseous screw implant does not exceed the dimensions of available bone. The long-term success of implants is a prime aim. To achieve this, it is essential for the initial evaluation of the dimensions of the resorbing alveolar process to be absolutely accurate. Ideally, an implant should be covered by at least 1 mm of bone on all sides. The major problem is estimating the thickness of bone, since the mucosal contour can mask the actual dimension of the alveolar ridge. Use of ridge mapping with the Wilson Bone Caliper makes possible a reliable evaluation procedure at the initial stage of treatment planning. PMID- 2599581 TI - Complete dentures fixed on dental implants: chewing patterns and implant stress. AB - Electrognathographic measurements on 18 patients with implant-attached mandibular complete dentures showed larger and more stable chewing patterns compared to their former dentures without implants. Strain gauge measurements revealed mechanical stress acting on the implants even during the fixation of the bar. In addition to simulating the periodontal ligament, the intramobile element (IME) of the IMZ system compensated minor, clinically undetectable mismatches inherent with technical procedures (casting, soldering). Although the implants are loaded with tensile and compressive stress, tensile stress dominated during the chewing process. The implants were also loaded during swallowing. This load reached half of the value of the chewing loads. PMID- 2599582 TI - Comparison of titanium-tantalum and titanium-niobium alloys for application as dental implants. AB - For the diffusion bonding of Ti alloys to alumina, materials with a similar thermal expansion coefficient to alumina are required. Such materials were developed by alloying the biocompatible elements Ta and Nb to titanium (Ti-Ta30 and Ti-Ta40, Ti-Nb40 and Ti-Nb50). While measuring the corrosion behavior of these alloys in 0.9% saline solution, no difference could be observed. The Ti-Ta alloys are superior in their mechanical properties to Ti-Nb alloys. PMID- 2599583 TI - In vitro substance loss due to galvanic corrosion in Ti implant/Ni-Cr supraconstruction systems. AB - To characterize the galvanic corrosion of supraconstructions consisting of Ni-Cr alloys that come in contact with titanium implants, the resultant substance loss was determined. The measurement of the released substance masses was conducted by analysis of the electrolyte solutions with the aid of atomic absorption spectrometry and by approximate calculation using current density time curves, according to Faraday's law. The results of this study show that both methods allow a clear differentiation of the corrosion behavior of various Ni-Cr alloys that come in contact with titanium. PMID- 2599584 TI - Mechanoperception of natural teeth versus endosseous implants revealed by magnitude estimation. AB - The psychophysical method of magnitude estimation was used to assess the sensitivity to applied force of natural teeth and Tubingen ceramic implants. It was shown that the power law holds for teeth and implants and that the averaged power functions were almost identical. PMID- 2599585 TI - Dynamic sterilization of titanium implants with ultraviolet light. AB - All implantable devices must be sterile. However, autoclaves produce poor surface properties that jeopardize the integration process. The application of a modified ultraviolet light source has proven to enhance bioreactivity by controlling surface properties, but it lacks validation of its sterilization capabilities. Forty-eight titanium implants were contaminated with spores of the biological indicator Bacillus stearothermophilus and subjected to "dynamic sterilization" by ultraviolet light. Forty-seven of the implants were successfully sterilized, as indicated by not producing turbidity in a suitable growth medium. This sterilization technique only requires a 20-second exposure to achieve sterility. PMID- 2599587 TI - A comparative study of results with various endosseous implant systems. AB - The results of regular follow-up of various endosseous titanium implant systems are presented together with an overview of the results with Tubingen Frialit aluminum oxide ceramic implants. Using ITI implants, pathological findings for sulcus depth and peri-implant bone degradation were found significantly more frequently than with the other titanium implants. Clinical mobility was present significantly more frequently with TPS implants than with the IMZ system, whereas an increase in the depth of the peri-implant sulcus alone occurred significantly more frequently with the IMZ and ITI than with the TPS implant system. The observation period for Branemark implants is too short to permit final evaluation. However, pathological findings have not occurred to date. PMID- 2599586 TI - The restoration of improperly inclined osseointegrated implants. AB - Improper implant angulation is one of the most difficult problems to overcome in the fabrication of implant-supported and implant-retained restorations. Several techniques using the "UCLA" abutment have been developed to solve these problems. The creation of large screw-access holes for moderate angulation and the fabrication of telescopic copings and overlay castings for severe angulation problems are discussed. PMID- 2599588 TI - Considerations for fluoride prescription supplementation within Orange County. PMID- 2599589 TI - Nutrition in preschool children: strengthen approach to promotion. PMID- 2599590 TI - Basic principles for control of acute respiratory infections in children in developing countries WHO/UNICEF. PMID- 2599592 TI - Evaluation of nutritional and immunization services in a tribal ICDS block of Rajasthan. AB - The evaluation of nutritional and immunization services was undertaken in the tribal ICDS block Kherwara (Rajasthan) by comparing the results of door to door surveys conducted on pretested schedules in six randomly selected Anganwadi Villages at the start (1983) and after completion of 4 years of the project (1987). A significant improvement (p less than 0.001) was found in nutritional status of children below 6 years of age. Except for BCG, the study revealed improved vaccination coverage. However, the achievements were far less than the targets laid under the National Health Policy. Concerted efforts are required to improve the services further for achieving the desired goals. PMID- 2599593 TI - Nutritional profile of preschool children of armed forces families around Hyderabad. AB - Three hundred and fifty three preschool children (1 to 5 years) belonging to armed forces families of non-officers (who often come from rural background) stationed at Military Station, Golconda, Hyderabad were studied for their clinical examination and anthropometric status. Diet survey by oral questionnaire was also carried out on a sub-sample of 48 children. The heights and weights of children from families of armed forces were far superior to those of rural Indian preschool children, but they were marginally shorter and lighter than those of well-to-do Hyderabad children. About 92% of the children had weights above 80% of Harvard median. The practical implication of these findings is that the children of rural families, with the usual socioeconomic constraints, when provided with steady income and comprehensive health care can be expected to achieve a growth status which is almost comparable to that of well-to-do children. PMID- 2599591 TI - A comparative study of different methods of training of rural subjects for reconstitution of oral rehydration solutions. AB - The efficacy of three methods of training rural women in reconstituting ORS was studied by analysing the sodium, potassium, and glucose contents of the ORS reconstituted by the three groups of rural women. The women in Group I were verbally instructed in the regional language regarding how to reconstitute the entire contents of a sachet containing oral rehydration salts in half a litre of water. Women from Group II, were given the same verbal instructions and in addition, were demonstrated the correct method of doing the same. Subjects from Group III were provided with plastic bags containing oral rehydration salts, which when filled with water upto the printed line, was expected to accommodate half a litre of water, when the bag was hung from a hook or held by another person from its upper ends. The contents of ORS reconstituted by Group II, who were demonstrated the actual procedure following verbal instructions, were near ideal followed by the ORS reconstituted by Group III and by Group I. PMID- 2599594 TI - Nutritional status of pre-school children of urban slum communities in Delhi. AB - Nutritional status of 486 preschool children residing in urban slums was assessed by making domiciliary visits. The overall prevalence of protein energy malnutrition (PEM) was found to be 81.8%, while 31.8, 44.1, 5.7 and 0.2% of children had Grades I, II, III and IV PEM, respectively. Age, sex and education had a significant association with PEM. PMID- 2599595 TI - Intra-uterine growth curves for midarm and thigh circumferences. AB - Use of birth weight as a measure of intrauterine growth is hampered by several logistic problems. Both mid-arm (MAC) and thigh circumferences (TC) have been proved to be efficient alternative measurements. In this study MAC and TC were recorded on 2925 consecutive live births to derive intrauterine growth curves and provide normative data for an indigenous population. PMID- 2599596 TI - Ratio of mid arm circumference to head circumference as a predictor of small for gestational age babies. AB - Birth weight (BW), mid-arm circumference (MAC), head circumference (HC) and MAC/HC ratio were evaluated in 845 term babies within 48 h of birth. MAC/HC ratio of less than 0.28 had a statistically significant sensitivity, specificity and predictive value (p less than 0.001) for identifying term small for gestational age babies. This ratio provides a simple, accurate and cheap way of screening SGA babies. This method may be employed for identification of SGA babies even by paramedical workers at community level. As with any other field index appropriate supervision and standardisation are essential for its usefulness. PMID- 2599597 TI - Comparative evaluation of two maternal weight-height indices during pregnancy. AB - Three hundred forty one primiparous women and their offsprings were the subjects of the study. Mothers were subjected to weight and height measurement as well as hemoglobin estimation. The weight for height ratio index (WHRI) and weight-height product index (WHPI) were calculated. Both WHRI and WHPI were studied in relation to birth weight (BW). WHPI was found to be superior over WHRI as it explained greater per cent variation in birth weight. The means for BW increased and incidence of low birth weight babies decreased significantly with increase of WHPI in each WHRI group. PMID- 2599598 TI - Blood pressure studies in Jaipur children. AB - A total of 1500 apparently healthy children between 1-12 years of age were examined. Blood pressure (BP) readings were taken and standard deviation and percentiles worked out for different sexes and age groups. Prevalence of hypertension was found to be 2.86% in males and 2.97% in females in 5-12 years of age group. Obesity was prevalent in 24% of the hypertensive cases. A higher value of serum cholesterol as compared to controls was also seen in the hypertensive group. PMID- 2599599 TI - Infants of diabetic mothers--an analysis of 50 cases. AB - In a prospective study of 50 infants of diabetic mothers, 40% were large, 44% appropriate and 16% small for gestational age, 36% were preterm, 24% of the mothers were managed by dietary modification, 62% received insulin, 10% were treated with oral hypoglycemic agents while 4% did not receive any treatment as they were diagnosed postpartum, 58% mothers, underwent cesarean section (38% elective and 20% emergency procedures), 34% had normal vaginal deliveries, 6% were delivered by forceps and 2% by vacuum. Sixty-four per cent were infants of gestational diabetic (IGDM) and 36% of preconceptional diabetic mothers (IPDM). The morbidity and mortality was lesser in IGDM compared to IPDM. Hypoglycemia was documented in 50%, polycythemia in 20%, birth asphyxia in 18%, respiratory distress syndrome and hypocalcemia in 14% each, transient tachypnea of the newborn in 12%, hyperbilirubinemia in 8%, congenital anomalies in 4% and cardiomyopathy, birth trauma and meconium aspiration in 2% each. Pretherapy serum insulin levels were estimated in 10 babies, and 6 babies were subjected to 2D echocardiography. The overall mortality was 20%. Infants born to mothers on oral hypoglycemic agents had a poor outcome. PMID- 2599600 TI - Serum copper in ICC and other hepatic disorders. PMID- 2599601 TI - T-lymphocytes in children with tuberculosis. PMID- 2599603 TI - Neonatal stridor--an unusual presentation of pulmonary air leak. PMID- 2599602 TI - Alcaptonuria with cleft lip. PMID- 2599605 TI - Renovascular hypertension in an infant. PMID- 2599604 TI - Those so-called still births. PMID- 2599606 TI - Pectus excavatum. PMID- 2599607 TI - Pulmonary aspiration of milk feed in a normal infant. PMID- 2599608 TI - Polio vaccination in developing countries. PMID- 2599609 TI - Poliomyelitis in vaccinated children. AB - Fifty-two children who had received at least 3 properly spaced doses of oral polio-vaccine and had developed acute poliomyelitis inspite of vaccination were studied clinically and serologically. This group (A) was compared with 28 children with poliomyelitis who had not received any vaccination (Group B). A much higher incidence of provocative injection and a better muscle power on presentation was seen in Group A as compared to Group B. Polio-virus type 2 was the commonest etiological agent in Group A (42.3%) whereas type I virus was most commonly seen in Group B (78.6%). A total 53.8% of cases of Group A had protective antibody titres to at least one poliovirus type in the acute phase sera, compared to only 4% from Group B. Six per cent from Group A had protective antibodies to all three virus types, disease in these cases was caused by non polio agents. Two cases in Group A were possibly vaccine induced paralysis. Recovery, after 60 days, was much better in Group A as compared to Group B. Mortality in the two groups was comparable. PMID- 2599610 TI - Immunization status in paralytic poliomyelitis--a hospital based study. AB - Six hundred and forty six cases in the age group 8-14 years suffering from paralytic poliomyelitis were analysed to find out the immunization status and its correlation with the incidence of poliomyelitis. In 382 cases where the immunization status was known, it was found that 325 (85.02%) cases were not immunized, 23 (6.02%) cases were partially immunized, while only 34 (8.9%) cases were fully immunized. The difference in the incidence of poliomyelitis between the vaccinated and non-vaccinated categories was found to be significant (p less than 0.001). PMID- 2599612 TI - Tuberculin sensitivity study in rural children around Davangere city. AB - Estimation of tuberculin sensitivity by Mantoux test was done in 3,000 children between 1-14 years from 4 villages adopted for Rural Orientation of Medical Education Programme by JJM Medical College, Davangere. 0.1 mt. of PPD RT 23 with Tween 80 equivalent to 1 TU was given intradermally over the left forearm and the results were read after 72 hours in all the 3,000 children given PPD. 97.4% of total children were BCG vaccinated. 15.4% of BCG vaccinated and 8% of non-BCG vaccinated showed positive tuberculin reaction with an overall positivity of 11.5%. Thus the prevalence rate of tuberculin infection in these rural children was very low. PMID- 2599611 TI - Study of diphtheria carriers in Miraj. AB - Following a case of diphtheria, 131 contacts were studied for throat and nose carriage. The carriage of C. diphtheriae was found to be 19.8%, 65.3% of them were toxin producing by counter-immunoelectrophoresis (CIEP). The carriers were treated with erythromycin for 7 days. Repeat swabs found them to be negative for C. diphtheriae except in four who had erythromycin resistant and penicillin sensitive strains. Penicillin treatment eliminated the organisms. PMID- 2599613 TI - Bacterial flora in mothers and babies with reference to causative agent in neonatal septicemia. AB - One hundred newborns and their mothers were subjected to aerobic bacterial cultures and sensitivity study from different sites. Out of 36 clinically suspected neonatal septicemia cases, the blood culture was positive for bacterial growth in 24 neonates. The incidence of septicemia in PT-AGA, FT-AGA, FT-SFD and postterm-AGA babies was found to be 50.0, 13.5, 28.1 and 50.0%, respectively. The incidence of septicemia in LBW and FT-AGA babies was found to be 45.3 and 13.5%, respectively. The single major isolate in the positive blood culture was Staphylococcus aureus. In Gram positive septicemia the commonest site for colonization of the same organism in newborn was found to be umbilicus followed by nose, throat and external auditory canal, while in Gram negative septicemia rectum and umbilicus were the commonest sites. PMID- 2599614 TI - Analysis of blood-culture isolates from neonates of a rural hospital. AB - All blood culture reports obtained from newborns admitted in a neonatal care unit during 1983-87 were reviewed to determine the current bacteriological profile of neonatal septicemia. A total of 1160 neonates of high risk category or having clinical features suggestive of septicemia were subjected to blood culture study during this period. The culture positivity rate was 73%. Of these, 24.9% cultures were polymicrobial. Among the 1059, growths obtained, 60.1% were Gram negative, with Klebsiella, E. coli and Pseudomonas as the commonest pathogens. In Gram positive group, coagulase negative Staphylococci were most frequent, constituting 24% of the total isolates. An increasing incidence of coagulase positive Staphylococci and Pseudomonas infections was observed in recent years. Another significant finding was a comparatively high prevalence of Group D beta hemolytic isolates among streptococcal growths, with S. fecalis as the single commonest streptococci isolate. PMID- 2599616 TI - Simplified home methods for the development of hand function in a cerebral palsied infant. PMID- 2599615 TI - Susceptibility of clinical isolates to cephalexin, cefazolin and cefotaxime. AB - Three hundred and seventeen recent clinical isolates were tested for in vitro susceptibility to the three cephalosporins available in India--cephalexin, cefazolin and cefotaxime by the Kirby--Bauer disc diffusion method. Cefazolin was the most effective cephalosporin against Gram positive cocci (71.8% sensitive) followed by cefotaxime (62.7%) and cephalexin (52.7%). Cefotaxime was very effective against commonly isolated Gram negative bacilli with only 10 (8.8%) isolates being resistant to it while 44 (39%) and 65 (57.5%) were resistant to cefazolin and cephalexin, respectively. All isolates of Pseudomonas aeruginosa were resistant to cephalexin and cefazolin and only 29 (32.6%) were sensitive to cefotaxime. PMID- 2599617 TI - Paralytic poliomyelitis in rural Kashmir. PMID- 2599618 TI - Magnitude of poliomyelitis in a rural area of Bangalore. PMID- 2599619 TI - Hepatic involvement in childhood tuberculosis. PMID- 2599620 TI - Porencephaly--a potentially avoidable complication of neonatal meningitis. PMID- 2599621 TI - Advantages of breast feeding--knowledge among paramedical health personnel and mothers. PMID- 2599622 TI - Antenatal diagnosis of asphyxiating thoracic dysplasia. PMID- 2599623 TI - Esophageal atresia with double tracheoesophageal fistula. PMID- 2599624 TI - Exchange transfusion with G-6-PD deficient donor blood causes exaggeration of neonatal hyperbilirubinemia. PMID- 2599625 TI - Oro-dental anomalies in Apert's syndrome. PMID- 2599626 TI - Sleep apnea in infancy. PMID- 2599627 TI - Effect of incentive scheme on immunization. PMID- 2599628 TI - Measles vaccine--controversy regarding the number of doses and storage conditions. PMID- 2599629 TI - Polio vaccination. PMID- 2599630 TI - National policy on immunizations. PMID- 2599631 TI - Enteric hepatitis. PMID- 2599632 TI - Tuberculosis and acquired immunodeficiency syndrome. PMID- 2599633 TI - Massive amoebic liver abscess. PMID- 2599634 TI - Breast milk secretion. PMID- 2599635 TI - Locking nailing: an aid to distal targetting. PMID- 2599636 TI - Mortality from interpersonal violence in Great Britain. AB - Data accessed from both death certificates and police reports show that mortality from interpersonal violence is extremely uncommon in Great Britain, particularly in comparison with other countries; in 1985, it accounted for only 0.1 per cent of all deaths and 0.4 per cent of deaths among individuals under 65 years of age. Despite a steady increase in the rate of homicide over the past 20 years, homicide can only be considered to be a minor public health issue in Great Britain. In contrast, data accessed from the British Crime Surveys and from studies conducted both in accident and emergency departments and among individuals hospitalized with head injuries, show that morbidity associated with interpersonal violence may be relatively common in Great Britain. However, until more valid estimates of morbidity can be made, the overall importance of interpersonal violence as a public health issue in Great Britain cannot be assessed with accuracy. PMID- 2599637 TI - Internal fixation of unstable spinal fractures: the Hartshill system. AB - The first 69 cases with a minimum of 1 year follow-up using the Hartshill system for the internal fixation of unstable spinal fractures (cervical 11, thoracic 8, thoracolumbar 42 and lumbar 8 are reported. The instrumentation is uncomplicated but attention to detail in technique is important. The system allows secure stabilization of the spine and early mobilization, irrespective of any neurological damage incurred in the primary injury. PMID- 2599638 TI - Eye injuries in coal mining. AB - The incidence of eye injuries in the coal mining industry in one British Coal Area in 1 year is presented and discussed. The discussion reviews the literature on eye injuries generally. The problems of ensuring adequate eye protection in mining operations are described: plans for a future survey to pinpoint critical areas are outlined. PMID- 2599639 TI - Spinal cord injury associated with blunt traumatic rupture of the diaphragm. AB - The incidence of spinal cord injury associated with blunt traumatic rupture of the diaphragm is extremely low and rarely mentioned in the numerous reports about rupture of the diaphragm. It is thought that more such cases can be found among the fatalities of aircraft accidents and presumably among the fatalities of road traffic accidents as the forces causing such injuries make it unlikely for the casualty to survive. The authors present six cases encountered at Stoke Mandeville Hospital, England, and at Sheba Medical Centre, Israel. Although the mortality of such cases, if the patient survives the original impact, is usually due to associated injuries, early diagnosis is essential as late complications increase the incidence of delayed mortality. PMID- 2599640 TI - Rapid technique for splenectomy. AB - The spleen is the most commonly injured organ in blunt trauma of the abdomen. In the haemodynamically unstable patient bleeding from a splenic injury, rapid control of the splenic hilum can be a technically demanding operation. We describe a technique which allows for rapid control of the splenic hilum and unhurried ligation of splenic vessels. This technique has been used on 30 patients without any complications related to splenectomy. It is most helpful when one is working with an inexperienced assistant. PMID- 2599641 TI - Sidewind reinforcement for above-elbow plaster slabs. AB - A method of reinforcing an above-elbow plaster slab is described. The technique prevents the splint becoming tight at the elbow and gives it considerable strength. PMID- 2599642 TI - Treatment of finger-tip injuries with silver sulphadiazine occlusion dressing. AB - From 1982, patients with finger-tip injuries were treated with sulphadiazine occlusion dressings. The average time taken for the wound to heal, incidence of infection and absence from work were studied. The results of this method gave consistently good results when compared with other techniques which are summarized. PMID- 2599643 TI - Symptomatic non-union of the carpal scaphoid: Matti-Russe bone grafting versus Herbert screw fixation. AB - We have reviewed 19 patients who have had Matti-Russe bone grafting and 16 patients who have had Herbert screw fixation for symptomatic non-union of the carpal scaphoid. The success rate in both groups was similar, 74 per cent in the Matti-Russe group and 71 per cent in the Herbert screw group. Only five patients in the Herbert screw group had bone grafts. The advantages and disadvantages of both methods of treatment are discussed. PMID- 2599644 TI - Hemiarthroplasty of the hip and dislocation. AB - A retrospective study was undertaken on 171 patients who had suffered a subcapital fracture of the neck of the femur between 1982 and 1986. The aim was to compare the dislocation rates in bipolar and monopolar endoprostheses. The basic surgical approaches were utilized: the posterior and direct lateral. Four endoprostheses were employed: Thompson's Moore's (monopolar), Monk's 'hard top', and Charnley-Hastings' (bipolar). There was no significant difference in the dislocation rates between monopolar and bipolar devices. It is concluded that the bipolar devices do not offer any additional protection against dislocation when compared with the traditional monopolar devices. PMID- 2599645 TI - Femoral shaft fractures in children: a prospective study of the overgrowth phenomenon. AB - All children with fracture of the femoral shaft treated from August 1978 to December 1983 inclusive, comprised the study series. The object of the investigation was to determine whether a relationship could be demonstrated between shortening at the time of healing and the magnitude of overgrowth during the following 2 years. Radiographic measurements of both lower limbs were carried out at 6 weeks and 6, 12 and 24 months after the accident. During the period of the investigation 109 children suffered femoral fractures. Of these, 67 (61 per cent) met the criteria for inclusion in the study. The investigation could not demonstrate any relationship between shortening at the time of healing and the magnitude of overgrowth 2 years later. Neither was it possible to demonstrate any relationship between sex, age, type of fracture, level of fracture, and the magnitude of the overgrowth. The mean overgrowth was 10.8 mm and the largest 26 mm. Almost all children who healed with little shortening showed no angulation, and their average age was considerably below that of the series as a whole, while almost all femoral shaft fractures which healed with considerable shortening had some angulation and the average age of these children was much higher than that of the whole series. The importance of angulation in respect of shortening after femoral shaft fracture in children has not previously been reported. PMID- 2599646 TI - Common carotid artery injury from an airgun pellet. PMID- 2599647 TI - Fatality from blind intubation of suspected tension pneumothorax. PMID- 2599648 TI - Delayed diagnosis of traumatic rupture of the spleen--a warning of the use of thoracic epidural analgesia in chest trauma. AB - Epidural analgesia is useful in controlling the pain from chest injuries. However, a case is presented where analgesia delayed the diagnosis of a splenic haematoma. Diagnosis was complicated by an initial negative peritoneal lavage. PMID- 2599649 TI - Traumatic indirect inguinal hernia: a seat belt injury. PMID- 2599650 TI - Mother to child transmission of hepatitis B virus in the Philippines. AB - A follow-up study of mother to infant transmission of hepatitis B virus was conducted in the Philippines between 1981 and 1983. The prevalence of HBsAg among 527 mothers was 8.5%. Overall, seven out of 17 (41.2%) infants born to HBsAg carrier mothers became HBsAg positive within the first 12 months of life. The risk of becoming HBsAg positive was about 20 times higher for infants born to HBsAg positive mothers than for infants born to HBsAg negative mothers (OR = 18.9, 95% Ci = 2.0-86.6). The risk was even higher if the mother was a carrier of both HBsAg und HBeAg (OR = 91.0, 95% Ci = 49.2-164.8). However, the risk of transmission was very low if the mother was an HBsAg carrier and anti-HBe positive. It was estimated that mother to infant transmission accounts for about one third of HBsAg positivity at one year of age. The implications of these findings in the planning of vaccination campaigns to prevent HBV infections are discussed. PMID- 2599651 TI - Septic osteomyelitis and polyarthritis with ureaplasma in hypogammaglobulinemia. AB - We describe a hypogammaglobulinemic woman with a one-year history of destructive septic osteomyelitis and polyarthritis with positive cultures for Ureaplasma urealyticum from joint exudate and blood. The clinical course was complicated by subcutaneous abscesses from which both U. urealyticum and Mycoplasma hominis were grown. Multiple routine cultures had been negative, except for sporadic findings of Staphylococcus epidermidis before specific cultures for mycoplasmas were performed. Therapy with beta-lactam antibiotics, clindamycin, rifampicin, fusidic acid and aminoglycosides had been given without obvious clinical effect. Intravenous doxycycline treatment instituted after microbiological diagnosis had a dramatic effect on the clinical course. The clinical suspicion of mycoplasma and ureaplasma as etiologic agents of orthopaedic infections in hypogammaglobulinemic patients is mandatory in order to perform appropriate cultures. PMID- 2599652 TI - Spinal cord compression due to Brucella granuloma. AB - Central Nervous System (CNS) involvement during the course of Brucella infection is a rare clinical condition. In this article, a patient with a progressive paraparesis syndrome with spasticity, who was treated by medical methods and surgical intervention is analysed. This patient suffered from spinal cord compression in the thoracal region caused by a Brucella granuloma. The patient had no evidence of systemic Brucella infection. PMID- 2599654 TI - Different serological HIV-2 results in three HIV-1-infected men from The Gambia. PMID- 2599655 TI - Comment on Prevalence of Hepatitis B Virus Markers among Polish Urban Alcoholics (Infection 16 [1988] 354-357) PMID- 2599653 TI - Comparative efficacy of ciprofloxacin, azlocillin, imipenem/cilastatin and tobramycin in a model of experimental septicemia due to Pseudomonas aeruginosa in neutropenic mice. AB - The in vivo activity of ciprofloxacin against Pseudomonas aeruginosa was studied in a septicemia model in neutropenic mice and compared to that of other antibiotics with established activity against P. aeruginosa. When given as a single agent, ciprofloxacin proved to be as effective as imipenem/cilastatin, whereas azlocillin and tobramycin were rather ineffective. After infection with higher challenge inocula, combinations of two (synergistic) antibiotics were more effective than single agent therapy in most instances. The combination of ciprofloxacin with azlocillin was at least as effective as that of imipenem/cilastatin with tobramycin. Selection of mutants with decreased sensitivity to ciprofloxacin occurred during therapy, however, post-therapy MICs of ciprofloxacin did not exceed a level of 1 mg/l and rises of MICs did not detrimentally influence treatment outcome. Taken together with the results of earlier studies, our data encourage the use of ciprofloxacin in gram-negative septicemia in neutropenic patients. PMID- 2599656 TI - Pulp response to, and cariogenicity of, a strain of Streptococcus mutans. AB - Gnotobiotic rats mono-infected with Streptococcus mutans (NCTC 10919) were maintained on a high sucrose diet in an isolator. When they were 8 weeks old the pulps of their maxillary first and second molars were mechanically exposed and left open to the oral environment. The rats were sacrificed in groups after 7 and 28 days. Thirty-seven teeth were available for study in the 7-day group, and 30 teeth in the 28-day group. The test S. mutans was non-cariogenic. After 7 days, necrosis of the superficial layers of the pulp was noted; however, after 28 days pulpal necrosis was much more extensive and calcific repair was observed in only one-third of the teeth examined. The microorganism did not provoke inflammation in the pulp or periapical tissues. This is the second strain of S. mutans tested in this manner. These results are very similar to those reported previously for S. mutans (NCTC 10449) and strengthens the view that organisms of the S. mutans group have a low pathogenicity for the pulp. PMID- 2599657 TI - The sealing ability of injection-moulded thermoplasticized gutta-percha. AB - The root canals of 120 single rooted teeth were prepared with files and then divided randomly into twelve subgroups. Four operators each filled three of these subgroups, one group with laterally condensed gutta-percha, one group with thermoplasticized gutta-percha with sealer and one group with thermoplasticized gutta-percha without sealer. The fillings were assessed radiographically and a dye penetration test was used to investigate the leakage. The lowest leakage values were found in those canals filled with laterally condensed gutta-percha. The sealing ability of thermoplasticized gutta-percha was enhanced by the use of a sealer. There was greater variation between operators in those groups where thermoplasticized gutta-percha was used. PMID- 2599658 TI - Root resorption in autotransplanted maxillary canine teeth. AB - The results of the endodontic management of root resorption in 77 transplanted teeth are described. Apical bony radiolucency healed in 75 per cent of cases but the prognosis for root resorption was poorer; in only 34 per cent of cases was the resorption arrested. Various factors which might have influenced the outcome of treatment are discussed. PMID- 2599659 TI - Three canals in the mesial root of mandibular first permanent molars: a clinical study. AB - Traditional teaching of the anatomy of root canals in different teeth can lead clinicians into the misguided belief that a predetermined number of root canals is always present in any given tooth. A new understanding of the root canal system has enabled the location of additional canals. Results of the clinical study of 760 first mandibular molars, showed that 20 (2.6 per cent) had three canals in the mesial root. Of these 20 teeth, 13 (65 per cent) had an intermediate canal which joined the mesiobuccal canal in the apical third. In six cases (30 per cent) it joined the mesiolingual canal in the same area. In only one case did the intermediate or third canal retain its individual nature and end in an independent foramen. PMID- 2599660 TI - The antibacterial properties of four elements released from dental restorative materials. AB - The antibacterial activity of four elements (zinc, copper, fluoride and mercury), previously reported to be released from dental restorative materials, was investigated. This was carried out using two aerobic micro-organisms isolated from dentine beneath cavities in the ferret. These were grown in the presence of the test elements over a concentration range of 10-100 micrograms/ml for 72 hours. Concentration and exposure time were found to have a highly significant effect on the growth and viability of both micro-organism. Zinc, mercury and copper exerted the greatest effect, fluoride the least. PMID- 2599661 TI - An in vitro method for comparing the effects of different root canal preparation techniques on the shape of curved root canals. AB - This study introduced an in vitro model which was designed to observe the effects of instrumentation on the shape of curved root canals. The model may be accurately rotated through 90 degrees allowing reproducible radiographs to be taken from two different angles. The root canals were filled with a radiopaque contrast medium before radiographs were taken. Two-dimensional evaluation of the shape of the root canals, before and after preparation was made on enlarged photographic prints obtained from the radiographs. A custom-made grid was used as a guide for measurement and accurate transfer from the pre- to postpreparation prints. Reproducibility of measurement was within 4 per cent. This method is feasible for quantitative comparison of the effect of instrumentation on the shape of root canals. PMID- 2599662 TI - The effect of hand, sonic and ultrasonic instrumentation on the shape of curved root canals. AB - This study compared the effects of hand, sonic and ultrasonic instrumentation on the shape of curved root canals in 60 extracted human lateral incisors and premolars. Each root of moderate or severe canal curvature was mounted onto a simulated crown and filled with a radiocontrast medium. Enlarged photographic prints obtained from radiographs taken before and after root canal preparation were measured. The results indicated a lower incidence of apical zip and elbow formation in the ultrasonic preparations when compared with those prepared by hand and sonic, irrespective of the canal curvature. A more prominent hour-glass shape was prepared by hand and sonic instruments particularly in severely curved root canals. A distinctive taper was produced by each method of preparation. All three instrumentation techniques showed preferential dentine removal from the convex aspect of the canal in the apical portion and the concave aspect in the middle portion of the root canal. PMID- 2599663 TI - A clinical and roentgenological study of 55 cases of root perforation. AB - The treatment outcome of 55 root perforations in man were related to pretreatment conditions and various treatment procedures used, with a mean recall period of 3 years 5 months. In this study maxillary teeth were perforated three times more often (74.5 per cent) than mandibular teeth (25.5 per cent); 47 per cent of the perforations were due to endodontic and 53 per cent due to prosthodontic treatment. The buccal and mesial root surfaces as well as the midroot areas were most often perforated. In 25 per cent, radiographic changes were directly related to the perforated areas. Twenty-eight perforations were repaired by orthograde fillings with gutta-percha and Kloro-percha N-phi; eight received a combined orthograde and surgical repair, and in only three cases a surgical approach was used. Four cases received no treatment but were recalled, and twelve perforations showed a size and location hopeless for repair; the teeth were therefore extracted. Five failures of the primary orthograde treatment group later underwent surgical treatment and were followed up for 3 years 3 months. The overall success rate in the primary treatment group of teeth was 56 per cent while 36 per cent became failures. Five failures were retreated, and four of these became successful. A combined orthograde and surgical repair of the perforations provided the most favourable outcome with 92 per cent successful. The study stresses the importance of preventing this type of treatment complication. PMID- 2599664 TI - Accelerated and malignant hypertension: experience from a large American inner city hospital. PMID- 2599666 TI - Aluminium kinetics during haemodialysis with the Redy 2000 Sorbsystem. AB - Aluminium kinetics of the Redy 2000 Sorbsystem using D3260 cartridges and the latest pre-treatment protocol have been studied in vitro and in vivo. In 7 patients, aluminium kinetics were studied during haemodialysis using the Redy 2000 Sorbysystem, D3260 cartridges. S557 acetate concentrate and Gambro hollow fibre dialyser (cuprophane 120M). The same patients were also studied during conventional haemodialysis using the Gambro AK10 proportionating system with acetate dialysate and Gambro hollow fibre dialyser (cuprophane 120M). There was no significant rise in plasma aluminium concentration during dialysis on the Redy 2000 Sorbsystem. The post-dialysis plasma aluminium concentrations were significantly higher after conventional haemodialysis, however, and the explanation for this is not clear but is not accounted for by differences in the degree of ultrafiltration during the studies. A significant rise in dialysate aluminium concentration was observed after 4 hours of dialysis on the Redy 2000 Sorbsystem. The manufacturer's ammonia test papers appear to be too insensitive as indicators of cartridge exhaustion and dialysate pH may be better. The D3260 cartridges should be used for a maximum of 4 hours only. Further long-term studies of aluminium kinetics using this system are justified. PMID- 2599665 TI - Are lipid abnormalities reliable cardiovascular risk factors in dialysis patients? AB - Patients on chronic hemodialysis often present both hyperlipidemia and a high incidence of cardiovascular disease (CVD). Uremic hyperlipidemia has usually been regarded as one of the most important cardiovascular risk factors (CVRF) in these patients. In order to study whether the "uremia-induced" lipid abnormalities are actually associated with evidence of uremic CVD, and consequently may be considered reliable CVRF, 123 patients on chronic dialysis were reviewed for the presence of CVD and, at the same time, examined for their lipoprotein pattern and other clinical and biochemical variables. Lipids and lipoproteins did not prove helpful in our study in identifying patients with CVD. Despite the fact that they had been on dialysis for a shorter time, CVD patients were significantly older and had higher blood pressure than patients without CVD. Our data suggest that the uremia-induced lipid abnormalities are not reliable markers of CVD in dialysis patients, and support the hypothesis that dialysis per se does not accelerate the atherosclerotic process in uremic patients. PMID- 2599667 TI - First-use reactions: a potential hazard for referral centers. AB - First-use reactions comprise a spectrum of adverse clinical signs and symptoms occurring in end-stage renal failure patients during hemodialysis treatments. This report describes four patients experiencing first-use reactions in the context of being referred to or from a tertiary care inpatient dialysis facility. Theories on the pathogenesis of first-use reactions are reviewed and recommendations for identifying patients at increased risk for this problem are proposed. PMID- 2599668 TI - Effects of keto-analogues on phosphocalcic and aminoacid metabolism in dialysed patients: a crossover study. AB - It has been suggested that calcium salts of keto-analogues (KA) have beneficial effects on phosphocalcic and aminoacid (AA) metabolism. To confirm this, their short-term effects were evaluated on chronic dialyzed patients. In a prospective, randomised, crossover study, eight and seven patients were put on KA (200 mg/kg/d) and assigned either a low-protein diet (LP:0.4 g/kg/d) or a normal one (NP: 1 g/kg/d) for 15 days. The two treatments were interchanged after 15 days of washout. KA.LP was accompanied by: a) decreases in calorie intake (12%; p = 0.001) and in blood concentrations of albumin (5%, p = 0.004), urea (32%, p = 0.001), phosphate (29%, p = 0.001), parathormone (27%, p = 0.008), isoleucine (24%, p = 0.04), 1 and 3 methyl-histidine (71%, p = 0.03; 24%, p = 0.005), valine (19%, p = 0.004) and hydroxyproline (85%, p = 0.009); b) increases in calcemia (9%, p = 0.002), cystathionine (991%, p = 0.0001) and threonine (22%, p = 0.04). KA.NP was accompanied by: a) decreases in phosphatemia (15%, p = 0.03) and parathormone (18%, p = 0.06); b) increases in calcemia (9%, p = 0.002), cystathionine (427%, p = 0.0001), and phenylalanine (28%, p = 0.013). Calcium salts of keto-analogues together with a low or normal protein diet thus seem to reduce blood concentrations of phosphates and parathormone, and raise calcium; however their action on aminoacids needs further investigation. PMID- 2599669 TI - Are changes in intracranial pressure during intermittent machine haemofiltration dependent upon membrane biocompatibility? AB - We measured the intracranial pressure, using a subdural catheter in three patients admitted with grade 4 hepatic encephalopathy following paracetamol (aminocetaphen) self poisoning. Acute oliguric renal failure was present in all cases and was treated with daily intermittent machine haemofiltration. Hypovolaemia prior to treatment was corrected and a total of 14 isovolaemic 17 litre exchanges carried out using either a Gambro FH77 (8) or Hospal 3600 (6) haemofilter. Intracranial pressure (ICP) increased during treatment with both types of filter, but the increase was greater in the Gambro FH77 treated group, mean ICP increased from 7.6 +/- 2 mmHg to 12 +/- 3 mmHg at 3 hours (p less than 0.05), this was associated with a greater fall in the percentage change from the pretreatment value of both arterial oxygen tension and total peripheral white blood cell count during the first hour of treatment compared to the Hospal 3600 treated group, 8 +/- 2% vs 1 +/- 2% (p less than 0.05) and 5 +/- 2% vs 3 +/- 2% (p less than 0.05). This suggests that membrane biocompatibility may also play a role in the development of increased intracranial pressure during intermittent machine haemofiltration. PMID- 2599670 TI - Mediastinal haematoma caused by subclavian catheterisation for haemodialysis. AB - A 59 year old woman developed a mediastinal haematoma after placement of a subclavian haemodialysis catheter. Vascular perforation by the guide wire used during catheterisation was the probable cause. The use of guide wires with a flexible J-shaped terminal portion is recommended to minimise this risk. PMID- 2599671 TI - Long-term increase in peritoneal membrane transport rates following incidental intraperitoneal sodium hypochlorite infusion. AB - A patient on continuous ambulatory peritoneal dialysis using an "O" set connection system with sodium hypochlorite as a disinfectant incidentally infused the disinfectant intraperitoneally on two occasions. The product of peritoneal membrane permeability and peritoneal membrane surface area increased after both infusions as judged by peritoneal equilibration test results and/or serum chemistries. Elevated peritoneal solute transport rates and reduced ultrafiltration gradually subsided but did not return to preinfusion values. This observation suggests that intraperitoneal sodium hypochlorite infusion may cause significant long-term alteration in peritoneal membrane transport characteristics. PMID- 2599673 TI - Late results of aortic valve replacement with Bjork Shiley prostheses: a comparison of standard aortic valve prosthesis with reversed mitral valve prosthesis implanted in aortic position. AB - Between 1976 and 1983, 435 patients underwent aortic valve replacement (AVR) with Bjork Shiley prostheses. Standard aortic Bjork Shiley prostheses (ABP) were used in 150 patients (Group I) and a reversed mitral Bjork Shiley prostheses in 285 (MBP in 250 and MBC in 35) patients (Group II). There was no significant difference in the number of the patients with valve calcification or the size of aortic root in the 2 groups. There was no significant difference in the early mortality in these two groups. The total follow up period in Group I was 912 years and 2130 years in Group II. The incidence of major aseptic prosthetic dehiscence and valve occlusion with tissue ingrowth were higher in Group I than in Group II. Reversed Bjork Shiley mitral valve prosthesis was successfully used in aortic position with reduced incidence of valve related complications. PMID- 2599672 TI - Oxalate bone disease--an emerging form of renal osteodystrophy. AB - Rosette-like arrays of highly birefringent calcium oxalate crystals are commonly seen in the marrow space of bone biopsy specimens taken from patients with primary hyperoxaluria, particularly if complicated by renal failure. Similar deposits have been described in chronic hemodialysis patients with secondary forms of oxalosis. Large multinucleated histiocytes may be seen surrounding these crystal deposits. Many of these cells are histologically indistinguishable from osteoclasts. We present a patient in whom this histiocytic reaction appeared to be of sufficient magnitude to stimulate bone resorption and to cause severe osteodystrophy. This observation, and those of other investigators reviewed in the discussion, suggest that oxalate deposition within bone may contribute to the pathogenesis of uremic osteodystrophy in chronic renal failure patients with primary or secondary types of oxalosis. PMID- 2599674 TI - Does cadmium contribute to the development of renal parenchymal hypertension? AB - In our study we investigated 36 out-patients with renal disease, 22 of whom were hypertensive. In all patients proteinuria was present (4.30 +/- 5.05 g protein/day) and kidney diseases were verified by renal biopsy. Blood cadmium in non-smokers was significantly (p less than 0.05) lower than in smokers. We found a positive correlation between cadmium-concentration of blood and urine (p less than 0.01, R = 0.44) and between cadmium-concentration of blood and blood uric acid (p less than 0.01, R = 0.44). Proteinuria was weakly correlated with cadmium concentration of urine (p less than 0.05, R = 0.35). Patients with renal hypertension showed a significantly higher (p less than 0.05) urine cadmium excretion per day (1.60 +/- 1.12 micrograms/day) compared to normotensives with a disease of the kidney (1.14 +/- 1.47 micrograms/day). Our results indicate that cadmium may be involved in the development of hypertension in patients with renal disease. PMID- 2599675 TI - Temperature and cardiovascular deaths in Montreal. AB - The incidence of mortality from myocardial infarction over a 2-year period in Montreal is examined in relation to temperatures and snowfall. Mortality is seen to increase with deviations from seasonally determined thermally neutral conditions, although compared to observations of a parallel study in subtropical Brisbane, death rates are lower with similar falls in temperature. In Montreal, mortality is also seen to increase with snow during the previous day. During anomalous cold spells death frequencies decrease, a phenomenon interpreted as the behavioural thermoregulatory process of cold avoidance. PMID- 2599676 TI - Climate and physiological heat strain during exercise. AB - A body-atmosphere energy exchange model (BIODEX) using heat transfer theory and empirical relationships is described which predicts the change in body core temperature during exercise as an index of thermal strain. Index values may be interpreted as the length of the period of activity before the heat load on the body causes internal body temperature to rise to critical levels. The performance of the model tested under controlled laboratory conditions using human subjects was found to be reliable. BIODEX is used to show the thermal significance of midsummer climatic conditions in New Zealand for those jogging outdoors. PMID- 2599677 TI - Effects of ascorbic acid supplementation on male reproductive system during exposure to hypoxia. AB - Two groups of male rats were exposed to simulated altitudes of 6060 m and 7576 m for 6 h/day for 7 days (intermittent exposure). In two additional groups of animals exposed to the same altitude, 100 mg of ascorbic acid (AA) was fed daily for 5 days prior to the exposure period and also during the exposure period. Rats that did not receive AA showed loss of body weight and weight of reproductive organs after exposure. Sex organs showed atrophy on histological examination and there was a deterioration in spermatozoal quality. There was an increase in alkaline and acid phosphatase, and decrease in protein, sialic acid and glyceryl phosphorylcholine content in various reproductive tissues after exposure. All the above changes in histology and biochemical composition could be partially prevented by AA supplementation. AA supplementation can therefore protect the male reproductive system from deleterious effects of hypoxia. The probable mechanism of action of AA is discussed. PMID- 2599678 TI - Abstracts of the twenty-seventh meeting of the Japanese Society of Biometeorology. Asahikawa, 31 October-1 November 1988. PMID- 2599679 TI - Differential drug use patterns among sexually abused adolescent girls in treatment for chemical dependency. AB - A sample of 444 girls admitted to adolescent chemical dependency treatment was divided into four groups based on sexual abuse experiences. Girls who reported intrafamilial abuse, extrafamilial abuse, or both, were compared with nonvictims in terms of alcohol and drug use histories. Prevalence and frequency of alcohol, marijuana, and cocaine did not differ significantly among the groups. However, all sexual abuse victims were significantly more likely to regularly use stimulants, sedatives, tranquilizers, and hallucinogens. Sexual abuse victims also reported earlier onset of alcohol and drug use, more self-medication, and more use to escape family problems. PMID- 2599680 TI - Reliability and construct validity of the needle sharing inventory. AB - The Needle Sharing Inventory (NSI) is a 59-item test developed to specify and assess behavior patterns associated with drug use and needle sharing. In order to determine its reliability and construct validity, the NSI was administered to 80 intravenous drug users (IVDUs) recruited from a methadone maintenance program in New York City. Patients were included in the study if they reported using intravenous drugs during the previous month. Factor analysis was performed indicating that 31 of the items loaded onto 6 factors similar to those hypothesized: four dealing with the social context of needle sharing - indiscriminate sharing, social sharing, intimate sharing, and use of shooting galleries; and two dealing with the emotional context of intravenous drug use negative affect states and positive affect states. These variables accounted for 71% of the total variance, suggesting internal consistency of these items. Factor scores significantly correlated to subjects' self-reported estimates of time using nonsterile needles and sharing needles. These data suggest that the NSI is both a reliable and a valid measure which may be used in future studies of intravenous drug use and needle sharing behavior patterns. The NSI may prove useful for the purpose of developing and evaluating interventions aimed at preventing or reducing the spread of HIV through needle sharing. PMID- 2599681 TI - From theory to practice: the planned treatment of drug users. Interview by Stanley Einstein. PMID- 2599682 TI - The Lexington addicts, 1971-1972: demographic characteristics, drug use patterns, and selected infectious disease experience. AB - The demographics, drug habits, and medical complications of a cohort of 1,129 addicts treated at Lexington in the period 1971-1972 were studied. These patients, admitted from 41 different states, had a mean period of addiction of 5.4 years. Over one-third of the sample had engaged in pimping or prostitution, and there were no differences by gender in terms of involvement. Eight-eight percent had shared injection equipment, and surprisingly, 78% admitted to some effort at sterilizing their "works." Hepatitis was the most common associated medical condition: 87% had serologic markers of hepatitis B virus (HBV) infection, 60% had evidence of hepatitis A virus (HAV) exposure, and 47% had abnormal liver function parameters. Gynecomastia was evident in 2% of male subjects. Thirteen percent of the sample had a reactive VDRL assay, but 64% of these were biologically false positive. Subtle abnormalities of immune function were also observed; 18% of the patients had recent unexplained weight loss, 6% had lymphadenopathy, 8% had leukopenia, and 2% had lymphocytopenia. We conclude that both HBV and HAV were important infectious disease risks in these addicts, and that many evidenced deficiencies in immune function well before AIDS became a major public health concern. PMID- 2599683 TI - Withdrawal sequelae to cannabis use. AB - A specific withdrawal syndrome resulting from the prolonged use of cannabis is presented. It is believed to be an underreported set of symptoms that are now emerging in the United States as a result of the increasing potency of the drug and greater numbers of long-term users. Two case studies are presented which illustrate the cannabis withdrawal syndrome in an otherwise healthy 25-year-old male and an exacerbation of a preexisting affective disorder in a 38-year-old male who prior to his resumption of cannabis use was asymptomatic for 3 years with antidepressant medications. The cannabis withdrawal sequela is presented with a discussion of differential diagnosis and implications for treatment and future research. PMID- 2599684 TI - Breath holding and success in stopping smoking: what does breath holding measure? AB - Breath-holding endurance has recently been shown to predict the outcome of an attempt at stopping smoking. This could reflect a relationship between breath holding endurance and the endurance of discomfort associated with cigarette withdrawal. However, it is not clear whether breath holding measures any such general trait. To see if it is related to another test of endurance, its correlation with maintained grip was examined. The two variables were closely related and remained so after differences in strength were partialled out. Breath holding appears to be a valid measure of endurance of physical discomfort. PMID- 2599685 TI - Women in treatment: changing over time. AB - The early 1970s marked the transition of experimentation with illicit drugs from a deviant behavior to a normative behavior among adolescents in the United States as well as the resurgence of the feminist movement in this country. A sample of 572 women from 21 treatment centers in 11 states was divided into two groups--age 35 and over, and under 35--to roughly correspond to whether they had reached adulthood before or after these cultural shifts. Younger and older women exhibit significant differences with respect to substance use patterns and prevalence of eating disorders, childhood antisocial behaviors, suicide attempts, and abuse by boyfriends and spouses. PMID- 2599686 TI - The effect of pre-bed care on alcoholic patients' behavior during inpatient treatment. AB - Sixty-five alcoholic patients admitted to an inpatient rehabilitation unit were studied regarding the effect of an outpatient pre-bed care participation program on subsequent behavior. There were no differences in on-ward behavior between the pre-bed care and direct admission patients. However, the pre-bed care patients were less likely to leave the inpatient unit AMA and more likely to still be active in aftercare treatment 6 months after discharge. PMID- 2599687 TI - Patterns of alcohol abuse among black and white alcoholics. AB - The drinking practices of a matched sample of 78 Black and 78 White, male, hospitalized alcoholics were compared. The groups were matched on age and educational level; and they were equivalent in terms of marital and employment status, number of times hospitalized for treatment of alcoholism and other neuropsychiatric disorders, and number of arrests. The Alcohol Use Inventory was used to assess drinking practices. Significant multivariate and univariate analysis of variance indicated that (a) Whites reported greater daily consumption of alcohol, a tendency to perceive alcohol as a means of relieving psychological distress, and a greater level of psychological distress as a consequence of alcohol abuse than Blacks; and (b) Blacks reported a tendency to perceive alcohol as a means to improve mental functioning and to experience more serious psychoperceptual withdrawal symptoms than Whites. PMID- 2599688 TI - [Effects of Chiari osteotomy on acetabular development in the growing subject. Experimental study in puppies]. AB - A Chiari osteotomy was performed on 10 dogs aged 2 months in order to assess the risks of mechanical or ischaemic loss of growth potential in the peri-acetabular cartilage. The development of the acetabular roof was studied by radiographs, microradiographs and histological assessment between 2 and 12 months. Apart from a few mechanical complications, the principal findings were the absence of any signs of necrosis, persistence of a strongly osteoblastic roof and readaptation of the trabecular pattern with articular remodelling, provided the mechanical conditions were satisfactory. The osteotomy must be sufficiently low, while remaining extra-articular, and adequate medial shift must be obtained. The interposed capsular tissue can then become dense and fibrous, providing a sliding surface. PMID- 2599689 TI - Biomechanics of the SB Charite lumbar intervertebral disc endoprosthesis. AB - The SB Charite intervertebral disc prostheses consist of two metal end-plates and an interposed polyethylene slide core. These were subjected to static and dynamic testing in a servohydraulic test rig. When embedded in polypropylene, the prostheses were found to function adequately under a high static load, and under a lighter dynamic load for a long time. When tested in a cadaveric vertebral segment, a large end-plate surface area proved to be of critical importance in preventing collapse of the prosthesis into the vertebral body. PMID- 2599690 TI - The anatomical pattern of gonarthrosis in Saudi Arabia. AB - Fifty patients in Saudi Arabia with primary gonarthrosis were randomly selected in order to study the anatomical pattern of the disease. Anteroposterior and lateral radiographs were taken with the patients nonweight-bearing and weight bearing; axial projections of the patello-femoral joint were also taken. Involvement of more than one compartment was significantly more common than it was in a Swedish series. The patello-femoral joint was affected in 80% compared with 48% of the Swedish knees. Different living habits are suggested as a contributory cause for the different patterns of gonarthrosis in the two countries. PMID- 2599691 TI - Comparison of isotonic saline, distilled water and boiled water in irrigation of open fractures. AB - A prospective randomised study was carried out on 86 patients with first, second and third degree open fractures in order to compare the effect of isotonic saline, distilled water and boiled water as irrigating fluids. The standard management consisted of emergency surgical toilet, use of broad spectrum antibiotics and fracture immobilization. The results show that the outcome was not affected by the type of irrigating fluid used. PMID- 2599692 TI - [Results of the surgical treatment of chronic hematogenous osteomyelitis of the humerus. A series of 46 cases]. AB - Forty-six patients with chronic haematogenous osteomyelitis of the humerus were treated surgically between 1968 and 1987. Operation involved decompression, sequestrectomy and saucerisation, and was always covered by between 10 and 60 days of antibiotic treatment. Forty-three patients were followed up for between 3 months and 20 years, 36 for more than 1 year. Thirty-nine patients achieved healing after one operation and 7 relapsed, of whom 6 healed after a second procedure. PMID- 2599693 TI - The bonding of glass ceramics to bone. AB - In this study the bonding behaviour of glass ceramics, containing apatite and wollastonite, to bone tissue is shown to vary depending on the amount of alumina they contain. We have experimented with three types of material: A.W-GC, AW-6 and AW-AL. Rectangular plates were implanted into the tibiae of rabbits. Ten weeks later a segment of bone around the plate was removed for examination, and the load of breaking by traction (failure load) was measured by an autograph. This was lowest for AW-AL and highest for A.W-GC (with AW-6 in between), and the figures differed significantly from each other (P less than 0.01). The interface was examined by a scanning electron micro-analyser and an energy dispersive X-ray micro-analyser (SEM-EPMA) and the reactive zone, the calcium-phosphorus rich layer, was assessed. Silicon and magnesium decreased, the calcium did not change, and the phosphorus increased. The reactive zone of A.W-GC was wider than that of AW-6. A Ca-P rich layer was not present between AW-AL and the bone. It is suggested that the strong bonding between glass-ceramics and bone was made through the formation of the Ca-P rich layer. PMID- 2599695 TI - Function after total hip replacement for primary osteoarthritis. AB - We have reviewed 505 cases of surviving total hip replacement for primary osteoarthritis and studied the functional result and pain relief obtained between four and fourteen years after implantation. The risk factors were stratified and evaluated by multivariate statistical analysis. The patients were satisfied with the result of arthroplasty, and long-term function was improved in 95% of cases. The risk of postoperative hip pain was increased by knee pain, a snap-fit prosthesis with a 35 mm head, and a short wedge-shaped femoral stem, and by replacement at an early age. Function was impaired postoperatively by hip pain, bilateral hip disorders, intercurrent disease affecting locomotion and by old age at the time of surgery. The functional result was not related to the time from operation. The functional result after hip arthroplasty can be evaluated in a logical, unbiased and thorough way using multivariate statistical analysis. PMID- 2599694 TI - [Study of the microscopic structure of the posterior ligaments of the lumbar spine]. AB - Biopsies of supraspinous ligaments (SSL), interspinous ligaments (ISL) and ligamenta flava (LF), removed at operation from 12 patients aged from 17 to 77 years, were examined by light microscopy, scanning electron microscopy and transmission electron microscopy. The structure of normal ligaments was first established, and then a comparison between normal and pathological ligaments was made. It was found that the SSL and ISL were composed of collagen, while the LF contained predominantly elastic fibres. In normal ligaments, a helical arrangement of the collagen fibrils was found. The fascicles were characterized by a regular waviness. Proteoglycan filaments were demonstrated in the three types of ligaments, forming a regular interfibrillar linking between adjacent collagen fibrils. Degenerative changes were found in most of the ligaments obtained from patients with disc herniation. On light microscopy, metaplasia into fibrocartilage and calcification was commonly seen. Ultrastructurally, the flattened fibroblasts were replaced by chondrocytic cells, and an accumulation of proteoglycans with a random arrangement and a cellular necrosis was encountered. The relevance of these degenerative changes to the mechanical properties and to low back pain is discussed. PMID- 2599696 TI - Long-term results after Colonna's operation. AB - A long-term review of 82 patients (117 hips) who had Colonna's operation for congenital dislocation of the hip has been carried out. Although early assessments had shown a high proportion of good results these deteriorated with time. At our latest review of 61 hips, with an average follow-up of 30 years, 34% had moderate, and 66% severe, osteoarthrosis; many of these patients now need a total hip replacement. We conclude that Colonna's operation is only indicated in a small number of cases. It should never be carried out over the age of 6 years, and only in younger children when there is severe underdevelopment of the acetabulum or where procedures which preserve the articular cartilage are unlikely to be successful. PMID- 2599697 TI - Structural changes in the socket of a Charnley low friction arthroplasty associated with recurrent subluxation. AB - Damage to the rim of the aperture of the socket in a Charnley low friction arthroplasty may be associated with recurrent subluxation or persistent dislocation of the femoral component. Impingement of the neck of the prosthesis against the socket or cement is the cause of this complication. The damage to the socket may require a full revision operation. PMID- 2599698 TI - Postural stability after total hip replacement. AB - Changes in postural stability were recorded before and after total hip replacement using a specially designed computer-assisted forceplate system. Twenty-one patients with unilateral osteoarthritis of the hip were randomised into two groups after operation with either a cemented Charnley or a non-cemented HP-Garches prosthesis. Postural stability was improved in both groups one year after operation and the sway pattern became normal. PMID- 2599699 TI - Single stage reconstruction of a large tibial defect using a free vascularised osteomyocutaneous ulnar transfer. AB - We present the case of a young man with 13 cm of bone and soft-tissue loss in the tibia and a severe traction injury of the brachial plexus. A free vascularised composite transfer of the bone and soft tissues of the ulnar side of the forearm was undertaken to reconstruct the defect. Bony union was achieved after a year and was followed by complete functional recovery of the lower limb. PMID- 2599700 TI - Patellar tendon bearing plaster casts in fractures of the tibia. AB - One hundred fractures of the tibial shaft were treated by early weight-bearing in a below knee patellar tendon bearing plaster cast. The rate of union, and the range of knee and ankle motion were assessed. Ninety-five per cent had good or excellent results. This method of treatment is particularly valuable in the third world because it avoids the complications of operation and also of traditional conservative methods. PMID- 2599701 TI - Temporary resection-arthrodesis of the knee using an intramedullary rod and bone cement. AB - A temporary arthrodesis of the knee, using an intramedullary Kuntscher rod and bone cement, was carried out in 76 patients after resection of tumours of the distal femur or proximal tibia. In contrast to primary arthrodesis with bone grafting, this procedure allows the patient to bear weight on a stable limb a few days after operation, reduces the risk of infection and avoids the negative effect of chemotherapy on graft incorporation. In 12 cases (16%) the implant failed mechanically by fracture, or by bending or migration of the rod, at from 13 to 54 months after operation. Deep infection occurred in 11 patients (14%). A second reconstruction was carried out in 14 patients, 10 using Kotz prostheses and 4 arthrodeses with bone grafting. The operation we describe has advantages for patients with high grade tumours which require chemotherapy and resection arthrodesis of the knee joint. PMID- 2599702 TI - Reduction of acute anterior dislocations of the shoulder without anaesthesia in the position of maximum muscular relaxation. AB - This paper describes the results obtained in treating 128 acute anterior dislocations of the shoulder by a method of reduction which obtains the maximum degree of muscular relaxation without general anaesthesia. Excellent results were obtained. Subcoracoid dislocations were more difficult to reduce than subglenoid. PMID- 2599703 TI - Operation for the stiff elbow. AB - Forty two cases of stiff elbow were treated by operation. Thirty three were subsequent to trauma, seven were due to ectopic ossification after quadriplegia, and two were associated with massive ectopic ossification after long term coma following head injury. Two separate skin incisions, postero-medial or medial and anterior, were used in most cases. In the post-traumatic cases, scarred, thickened posterior oblique fibres of the medial collateral ligament were usually found. Ectopic ossification was frequently situated on the postero-medial aspect of the stiff elbows. Resection of the thickened fibres or the ectopic ossification was the most effective procedure to improve elbow flexion. The average improvement in range of motion was 59 degrees in post-traumatic cases, 72 degrees in ectopic ossification after quadriplegia and 127 degrees in ectopic ossification following coma. PMID- 2599704 TI - Unicameral bone cysts. Natural history and the risk of fracture. AB - Unicameral bone cysts in 57 patients, seen at the Alfred I. duPont Institute between 1949 and 1982, were studied retrospectively. We present the natural history in several patients and report a "cyst index" which allows the progress of the cyst to be followed and makes it possible to determine whether there is a significant risk of fracture which would warrant treatment. We have found that measuring the cyst index in patients treated by injections of methylprednisolone acetate helps to assess the response to treatment. PMID- 2599706 TI - Group psychotherapy and pharmacotherapy: psychodynamic considerations. AB - Perspectives on the psychology of pharmacotherapy are much broader in therapy groups than in the dyadic relationship of individual psychotherapy. The author draws on several sources to develop descriptions of the possible psychodynamic effects of pharmacotherapy on group members for whom medication is prescribed, those for whom it is not prescribed, the group as a whole, and group leaders. In the context of dependency and other conflict sources, anxiety and attendant control issues generated by the collective meanings of medication can result in significant group denial and/or regression. This article underscores the importance of group leader awareness of the potential impact of pharmacotherapy on group dynamics and endorses ongoing therapeutic attention to these often subtle influences. The author suggests further study of the meanings of medication, their influences on individual and group dynamics, and the interventions considered most therapeutic. PMID- 2599705 TI - Spring alloplasty in the treatment of fractures of the thoracic and lumbar spines. PMID- 2599707 TI - The group as an object in the cultural field. AB - This paper illuminates the interplay between group and individual processes by exploring members' notions of the group itself. What members hold in common about the "group" is understood as an object in the cultural field, which is a particular kind of transitional phenomenon (Winnicott). The paper connects this notion to Bion's concept of "basic assumptions," and describes members' motivations for creating the "group" as well as its role in the psychotherapy group. The object in the cultural field is then further elaborated in its more general role in the relation between the individual and the group, which leads to a consideration of psychotherapy groups in terms of their value in facilitating living in the social world. PMID- 2599708 TI - Hostility in group psychotherapy. AB - To run a psychodynamic group therapeutically, the leader must understand the meanings and functions of hostility. Fundamental to this task is the leader's awareness of his or her bias toward hostility as a constructive or destructive feeling and willingness to serve as a lightening rod for it. This paper discusses the sources of hostility during different stages of group development. The therapeutic handling of hostility is discussed under the following topics: theoretical considerations, defensive functions, and communicative functions. Case examples illustrate the proper handling of contractual violations, scapegoating, and narcissistic injury. Countertransference reactions to anger and rage in the group are discussed. PMID- 2599709 TI - Short-term outpatient therapy groups for schizophrenics. PMID- 2599710 TI - Guidelines to minimize premature terminations. PMID- 2599711 TI - An introduction to the work of Didier Anzieu. PMID- 2599712 TI - Critique of A. Alonso and J. S. Rutan "The Experience of Shame and the Restoration of Self-Respect in Group Psychotherapy" (January, 1988), and their rejoinder (July, 1988). PMID- 2599713 TI - The effect of 3,6-bis(2-piperidinoethoxy) acridine trihydrochloride (CL 246, 738) on acute graft vs host reactions in mice. AB - 3,6-Bis (piperidinoethoxy) acridine trihydrochloride (CL 246, 738) prevented the development of graft vs host (GVH) disease in normal BDF1 mice injected with C57BL/6 parental spleen cells. A single oral dose (50 mg/kg) given on day 0 or day -1 of GVH induction prevented the day 10 GVH-associated suppression of mitogen responsiveness and IL-2 production. The drug was ineffective if given later (days 3-7) in the reaction. The protective effect of CL 246,738 was neutralized by injecting drug-treated GVH mice with antibody to asialo GM-1 (ASGM 1). This suggested that the protective mechanism was not due to a direct effect of the drug on donor cells but rather was achieved indirectly through the activation of host ASGM-1+ cells which then rejected donor lymphocytes. This hypothesis was supported by immunofluorescence which showed that the donor-host chimerism seen in control GVH mice was not found in drug-treated GVH mice. Direct verification of this hypothesis was provided by data which showed that the transfer of CL 246, 738-activated large granular lymphocytes from normal F1 mice can prevent donor-induced immunosuppression in GVH mice. The results suggest that CL 246,738 is a potent immunostimulant which can boost natural resistance of normal unirradiated mice. PMID- 2599714 TI - Immunomodulation by orally administered beta-glucan in mice. AB - Orally administered SSG, a beta-1,3-glucan obtained from the culture filtrate of the fungus Sclerotinia sclerotiorum IFO 9395, was examined for effects on immune responses in mice. The proliferative responses of spleen cells from SSG administered mice (40 or 80 mg/kg, daily for 5 or 10 consecutive days) to a T cell mitogen, concanavalin A (Con A), or a B-cell mitogen, lipopolysaccharide (LPS), were higher than those from normal mice. Oral administration of SSG (80 mg/kg) to mice also enhanced the activities of both natural killer (NK) cells in spleen and the lysosomal enzyme of peritoneal macrophages. Furthermore, significant inhibition of tumor growth was observed in syngeneic tumor systems when SSG was administered directly after tumor implantation. The inhibiting effect required high doses of SSG (over 80 mg/kg). These results demonstrate that SSG can potentiate the immune response of mice following oral administration. PMID- 2599715 TI - Effect of a traditional Chinese herbal medicine ren-shen-yang-rong-tang (Japanese name: ninjin-youei-to) on hematopoietic stem cells in mice. AB - Cell dynamics after intraperitoneal (i.p.) and oral administration of a traditional herbal medicine, ren-shen-yang-rong-tang (Japanese name: ninjin-youei to, NYT), were investigated. When NYT was injected i.p. into C3H/He mice, numbers of spleen and peritoneal cells significantly increased in a dose-dependent manner and showed high levels from 4 to 21 days. Two peaks in the total cell number were observed on days 7 and 14 in the peritoneal cavities and spleen of C3H/He mice administered NYT. A marked accumulation of PMN cells in the peritoneal cavity and spleen was detected at 7 days after injection. The numbers of macrophages and lymphocytes also increased by i.p. administration of NYT. The thymus cell number decreased transiently between 4 and 7 days and thereafter returned to the control level. No significant change in the cell number of lymph nodes was observed. Such cellular accumulation was also detected in C3H/HeJ mice, a nonresponder strain to bacterial endotoxin, and athymic nude mice. The activity of colony-forming units in the spleen (CFU-S) of C3H/He as well as C3H/HeJ mice was markedly augmented by i.p. administration of NYT. NYT induced significant CSF production as detectable by its activity in the sera. In addition, oral administration of NYT for 10 days induced a significant increment of peripheral leukocytes and spleen cells and enhanced CFU-S activity of bone marrow cells as induced by i.p. administration, indicating that NYT acts on hematopoietic stem cells capable of differentiating to lymphocytes, macrophages and PMN cells into the periphery. PMID- 2599716 TI - Characterization of the immunoregulatory properties of thymosin alpha 1 on interleukin-2 production and interleukin-2 receptor expression in normal human lymphocytes. AB - Thymosin alpha 1 (T alpha 1) and thymosin fraction 5 (TF5) have been shown to induce lymphocyte maturation and differentiation as well as to modulate mature immune responses to antigens and mitogens. The present study focused on the characterization of the mechanisms involved in T alpha 1 and TF5 enhancement of phytohemagglutinin (PHA)-induced interleukin-2 (IL-2) secretion and interleukin-2 receptor (IL-2R) expression in human mononuclear cells. We provide evidence that TF5 and T alpha 1 modulate an early event(s) during lymphocyte activation by mitogens. A short preincubation period (30 min) of non-adherent cells with thymosins, followed by extensive washing and subsequent exposure to PHA, was sufficient to enhance the production of IL-2 and the expression of IL-2R induced by the mitogen. Furthermore, the concomitant addition of PHA and thymosin during the preincubation period is not necessary for the enhancing effects to occur. We have also studied the role of macrophages on thymosin modulation of these responses. Results presented here indicate that macrophages are not essential for the interaction of thymosins with T-cells. However, macrophages are an absolute requirement during the exposure to the mitogen after preincubation with thymosins for the manifestation of TF5- and T alpha 1-mediated enhancing effects on IL-2 production and IL-2R expression. Human recombinant interleukin-1 beta (rIL-1 beta) was able to replace this macrophage requirement, indicating that production of IL-1 by these cells is a critical event in thymosin modulation of the IL-2 system. Two-color flow cytometric analysis and experiments involving the use of highly purified helper/inducer (Th, CD4+) and cytotoxic/suppressor (Tc, CD8+) T cell populations indicated that both, Th and Tc cell populations are targets of thymosin activity. These studies provide additional evidence that thymosins play an important role in the modulation of the normal immune response and begin to define the mechanisms underlying T alpha 1 immunoregulatory properties. PMID- 2599717 TI - Effects of the newer antifungal agents (bifonazole, ICI 195, 739 and amorolfin) on in vitro phagocytic, lymphocytic and natural-killer cell responses. AB - Amphotericin B and some of the imidazole drugs have been shown to suppress certain neutrophil and lymphocyte functions both in vitro and in vivo. We present here the in vitro effects of: amorolfin, a morpholine derivative; the imidazoles clotrimazole and ketoconazole; the N-substituted imidazole bifonazole and a triazole (ICE 195, 739), on neutrophil and lymphocyte function. All of these drugs inhibited neutrophil random migration, chemotaxis and hexose monophosphate shunt activity. The effects of the drugs on neutrophil adherence, deoxyglucose transport and beta-glucuronidase release were variable while lysozyme release was unaffected. Natural Killer cell cytoxicity was depressed by all drugs tested except for amorolfin. Mitogen-induced lymphocyte blastogenesis was suppressed by all the antifungal drugs tested. Similar results were obtained using the mitogens phytohaemagglutinin, concanavalin A and pokeweed mitogen. The mechanism of action of these drugs on these cell functions remains unknown, there may be a correlation between their effects on fungi and their effects on leukocytes. Clearance of systemic fungal infection is heavily dependent on integrity of the cellular immune system and it is clearly undesirable that antifungal drugs have immunosuppressive properties. Further studies are required to determine the in vivo and clinical relevance of our observations. PMID- 2599718 TI - Effects of the immunomodulator PSK on growth of human prostate adenocarcinoma in immunodeficient mice. AB - Tumor growth alterations were studied using an immunomodulator, PSK. Four human prostate tumor lines were grown in two types of immunodeficient mice. Two of the lines were selected because they are able to metastasize to lungs in host animals. Outbred NIH Swiss athymic mice having normal natural killer cells and athymic Beige mice deficient in natural killer cells were used as animal hosts. PSK treatment was given to tumor-bearing hosts to some animals soon after solid tumors were injected and to others after solid tumors were well-established. Low dose cyclophosphamide was given to some animals to decrease host natural killer cells and polyinosinic-polycytidylic acid (poly I:C) was given to other animals to increase natural killer cell activity. Measurement of tumor doubling times, host survival and metastatic capabilities showed that either poly I:C or PSK treatment in NIH Swiss animals soon after tumor cells were injected significantly increased tumor doubling times and host survival and decreased the incidence and number of metastatic lung lesions. Two of the tumor lines incapable of metastasizing in NIH Swiss mice were metastatic in the Beige athymic, natural killer-cell-deficient animals. PMID- 2599719 TI - Effects of long-endurance running on immune system parameters and lymphocyte function in experienced marathoners. AB - The extent and duration of changes in leukocyte subsets, lymphocyte subpopulations, spontaneous blastogenesis, cortisol, and catecholamines were measured in ten experienced marathoners, who ran 3 h to exhaustion in a laboratory setting. Blood samples were taken at baseline, 1 h of exercise, and 5 min, 1.5 h, 6 h, and 21 h of recovery. The 3-h endurance run was associated with significant leukocytosis, granulocytosis, neutrophilia, monocytosis, and eosinopenia during recovery. All of these parameters except for eosinophils returned to normal by 21 h of recovery. Total lymphocyte count increased 31% at 1 h of exercise, then decreased 19% at 1.5 h of recovery when compared with baseline values. T cell count showed no significant changes, but B cell lymphocytosis was measured at 5 min and 6 h of recovery. T helper/T suppressor ratio (H/S) was significantly elevated 39% at both 1.5 h and 21 h of recovery due to the decrease in number of T suppressor cells. Spontaneous blastogenesis was significantly increased 52% by 1 h of exercise and remained elevated throughout recovery. The increase in cortisol from baseline to 1.5 h of recovery correlated positively with the increase in both total leukocyte count (r = 0.78, P = 0.008) and granulocyte count (r = 0.81, P = 0.005). Our results suggest that exhaustive endurance exercise in marathon runners is associated with many significant perturbations in immune system parameters, most of which return to normal levels at 21 h of recovery. PMID- 2599720 TI - Adaptation of the "Conconi test" to children and adolescents. AB - A field test for the determination of anaerobic threshold (AT) based on the relationship between work intensity and heart rate was previously developed in adult runners (4) and then applied in various sports activities (3, 5, 9). In the current study the same relationship between running speed (S) and heart rate (HR) was determined in 274 healthy children and adolescents (169 males and 105 females). All tests were performed either outdoors on a 400-m track (n = 159, 110 males and 49 females) or indoors in a gymnasium (n = 115, 59 males and 56 females). The subjects increased their work intensity progressively from low to submaximal speeds. HR was determined by a heart rate monitor (Sport Tester TM PE 3000, Polar Electro, Kempele, Finland). In every subject examined, the linearity of the S-HR relationship was lost at a speed, called deflection speed (Sd), above which the increase in S exceeded the increase in HR. HR at Sd was defined as HRd. The respective test-retest correlation coefficients for Sd, HRd, and slope of the linear part of the graph were 0.990, 0.824, and 0.953 when determined outdoors and 0.996, 0.840, and 0.932 when determined indoors. The outdoor-indoor correlation coefficients were 0.934, 0.855, and 0.282, respectively, for Sd, HRd, and slope. The results suggest that application of this test to children and adolescents in running may prove useful in cross-sectional and longitudinal studies of the development of aerobic power during growth. PMID- 2599721 TI - A field test for determining the speed obtained through anaerobic glycolysis in runners. AB - A field test for the evaluation of the speed generated by the anaerobic lactacid mechanism has been developed in runners. The test consists of 1200 m of continuous running: in the first 1000 m the speed corresponding to the anaerobic threshold is progressively reached; in the last 200 m an all-out sprint is performed. The speed at the anaerobic threshold is subtracted from the speed reached in the final 200-m all-out sprint. In 39 runners examined (marathon runners, n = 13; 5000-10000-m runners, n = 10; 400-800-m runners, n = 7; sprinters, n = 9), the additional speed generated above the anaerobic threshold was correlated with the venous blood lactate concentration reached 5 min after the all-out effort (r = 0.93). The anaerobic speeds measured by the test were in keeping with the characteristics of the runners under study, i.e., anaerobic speeds were highest for the sprinters, intermediate for the middle-distance runners, and lowest for the marathon runners. Since the speed generated above the anaerobic threshold by the aerobic fuel breakdown can be subtracted, the contribution of creatine phosphate is minimal, and the speed exceeding the anaerobic threshold is highly correlated with lactate accumulation, the present test should measure the speed generated by anaerobic glycolysis. PMID- 2599722 TI - Effect of training load on OBLA determination. AB - Fifteen male long-distance runners, 35.9 +/- 8.2 years of age, participated in the study. They had 5.7 +/- 2.3 years of running experience, marathon best time of 2,58:51 +/- 0,14:45 h, 10-km personal record of 37:18 +/- 2:50 min, and maximal aerobic power of 64.6 +/- 5.8 ml.kg-1.min-1. Their 4 mM.l-1 lactate threshold (OBLA) was tested twice in a randomized order: once following a week of light, pre-race-like training, and once after a week of heavy training load. The parameters measured during the OBLA tests were: rating of perceived exertion (RPE), running economy (E), heart rate (HR), respiratory exchange ratio (R), and running velocity at OBLA. Compared with the light load treatment, RPE following the heavy training week rose by 0.8 units, HR and E remained unchanged, and R decreased slightly (0.012). Running velocity at OBLA was raised 0.42 km.h-1 by the heavy training, but a negative correlation was found between this change and the baseline (light load) OBLA velocity (r = -0.57). It is suggested that in athletes the usefulness of OBLA testing, aimed at assessing current performance capacity, could be compromised by lack of control over the immediately preceding training schedules. However, it appears that the susceptibility to the lack of such standardization may be reduced or absent in higher level runners. PMID- 2599723 TI - Reduction of Hb levels during the racing season in nonsideropenic professional cyclists. AB - Hematological variables of 40 professional cyclists, all receiving intravenous iron supplementation, were followed during a 15-month period. Mean values for red blood cells (RBC), hemoglobin (Hb), and hematocrit (Ht) were significantly lower during the racing season (RS) than during the nonracing periods (NRP) (RBC: RS = 4.53 +/- 0.34 millions/mm3, NRP = 5.09 +/- 0.36 millions/mm3; line 7 of abstract: Hb: RS = 14.2 +/- 0.9 g/dl, MRS = 15.2 +/- 0.9 g/dl; Ht: RS = 40.7 +/- 2.7% NRP = 44.4 +/- 2.9%; P less than 0.001 for all). However, mean values for ferritin and mean corpuscular hemoglobin (MCH) were significantly higher during the racing season (ferritin: RS = 422 +/- 398 ng/ml, NRP = 311 +/- 321 ng/ml, P less than 0.05; MCH: RS = 31.5 +/- 1.3 pg, NRP = 30.0 +/- 1.4 pg; P less than 0.001). These results suggest that the reductions in RBC, Hb, and Ht found in professional cyclists during the racing season are not the consequence of a diminution of iron stores but rather of reduced erythropoiesis and increased RBC destruction. PMID- 2599724 TI - Effects of long-distance running on iron metabolism and hematological parameters. AB - In 110 well-trained participants of a 1000-km running competition lasting for 20 days hematological parameters, iron metabolism, and their respective changes during the race were investigated. Thirty-nine men and 11 women were accustomed to wholesome vegetarian food (lacto-ovovegetarian), 52 men and 8 women consumed a conventional western diet. In each group 50% of the runners finished the race. Before the competition started red blood cell count, hematocrit, and hemoglobin were on average below the values observed in the normal population in all groups. Both male and female runners consuming the wholesome diet showed significantly lower ferritin values than those on a western diet. During the first days of the competition hemolysis occurred leading to increased serum concentrations of bilirubin and iron and decreased haptoglobin levels. Hb concentrations showed a constant decrease during the race. Serum ferritin concentration rose about twofold within the first days and then decreased again without reaching pre-race levels. Serum iron concentrations showed a significant decrease between days 3 and 6. Iron loss was caused by hematuria (25% of all urines tested), gastrointestinal blood loss (10% of all stool specimens tested), and by sweating (4.5 micrograms iron/dl sweat). Our results suggest that especially in female long-distance runners it may be difficult to supply sufficient quantities of iron with the diet. PMID- 2599725 TI - Effect of endurance training on cardiovascular response to static exercise performed with untrained muscles. AB - Eighteen male volunteers (20-23 years) were submitted to 13 weeks of training consisting of 30 min of exercise (at 50%-75% VO2max) on a bicycle ergometer, performed three times a week. Every 4 weeks the heart rate (HR), blood pressure (BP), and systolic time interval (STI) responses to the static handgrip (at 30% MVC) were examined. Before and after 13 weeks of training echocardiograms were recorded in seven subjects at rest and during the handgrip. Significant decreases in HR and BP responses to static exercise were found already after 4 weeks of training. Resting STI and left ventricular dimensions were not affected by training, but during the static exercise the pre-ejection period (PEP) and isovolumic contraction time interval (ICT) at the corresponding HR were significantly shortened after 8 weeks of training. The values of echocardiographic indices of left ventricular function obtained during exercise after training did not differ significantly from those found before training. It is concluded that endurance training of moderate intensity improves cardiac function during static exercise performed with untrained muscles. PMID- 2599726 TI - Epidemiology of injuries in Danish championship tennis. AB - During the outdoor tennis season of 1984 a prospective injury registration was done in 104 randomly chosen elite tennis players, of whom 86% could be followed. We found 46 injuries: an incidence of 2.3 injuries/player/1000 tennis hours. Men were more frequently injured than women. The prevalence was 0.3 injury/player. Upper extremity injuries were most frequent - 45.7% (21/46). Shoulder injuries were the single most frequent injury - 17% (8/46). The pathophysiology was overuse in 67% (28/42), strains in 14% (6/42), sprains in 17% (7/42), fractures in 2% (1/42), and blisters in 5% (2/42). Players using conventional rackets had more injuries to the upper extremity compared with players using mid/oversized rackets, though the difference was nonsignificant. The importance of impact forces from the tennis stroke in the mechanism of upper extremity injuries is discussed. PMID- 2599727 TI - Marathon running: functional changes in male and female subjects during training and contests. PMID- 2599728 TI - Marathon running: functional changes in male and female subjects during training and contests. Introduction. PMID- 2599729 TI - Statistical methods used in the marathon study. AB - In this note an outline is given of the statistical methods which were used in the marathon study. The techniques are: box-and-whisker plots, several nonparametric tests, and methods for assessing the intraindividual variations and critical differences. PMID- 2599730 TI - Effects of endurance training and competition on exercise tests in relatively untrained people. AB - One hundred fourteen subjects (34 +/- 8 years) without any competition background took part in an endurance training study to be completed after 1.5 years with running a marathon. Ultimately, 60 males and 18 females achieved that goal. The training program, carefully supervised, was divided into three phases with a maximum of 45, 70, and 110 km/week training volume and concluded with a performance race of 15, 25, and 42.195 km, respectively. Three days before and 3 and 5 days after each race, 35 subjects were selected to perform a progressive treadmill test and the remaining subjects participated in performing field tests of running 400 and 1000 m. The maximal velocity achieved in the treadmill test was 4.75 +/- 0.36 m.s-1 for males and 4.18 +/- 0.28 m.s-1 for females; it remained constant throughout the study. However, the running velocity at 4 mmol.1(-1) plasma lactate concentration increased about 10% from phase 1 to 3. In the females this rise already appeared to be completed in phase 2. Heart rate showed a tendency to increase at both submaximal and maximal exercise from training phase 1 to 2 and 3, whereas plasma lactate concentration showed a decreasing tendency. Three days after the 25 km and the marathon race the maximal running velocity in the exercise test was 2%-4% lower compared with the pre-race test (P less than 0.05). Five days after the race this difference again faded away. This small decline in running performance was not reflected in changes of physiologic responses such as heart rate or plasma lactate concentration. PMID- 2599731 TI - Plasma urea, creatinine, uric acid, albumin, and total protein concentrations before and after 15-, 25-, and 42-km contests. AB - One hundred fourteen volunteers (34 +/- 8 years) took part in an endurance training study to be completed after 18-20 months with a marathon. Ultimately, 60 males and 18 females achieved that goal. The training program, carefully supervised, was divided into three periods with a maximum of 45, 70, and 110 km/week training volume and concluded with contests of 15, 25, and 42.2 km, respectively. The competitive distance always exceeded the maximal distance covered in any previous training session. Three days before and 3 and 5 days after each race 35 subjects were selected to perform a progressive treadmill test and the remaining subjects participated in field tests of 400 and 1000 m. Before and after three contests of 15, 25, and 42.195 km the plasma concentration of urea, creatinine, uric acid, albumin, and total protein were determined. Both sexes demonstrated an increase of the plasma concentrations of urea, creatinine, and uric acid after the contests. Plasma albumin concentration decreased 2 days after the contests and total protein did not change. In females the decrease of the elevated plasma urea concentration after the marathon from the 1st day to the 3rd day post-exercise was faster than in males. The increase of plasma creatinine and uric acid concentrations were hardly dependent on the contest's distance. PMID- 2599732 TI - Effect of training and 15-, 25-, and 42-km contests on the skeletal muscle content of adenine and guanine nucleotides, creatine phosphate, and glycogen. AB - Thirty-four nonathletic volunteers (23 males and 11 females) were subjected to a training program aimed at completing a marathon run within 18-20 months after the onset of training. During the course of the training the content of ATP, creatine phosphate, GTP, GDP, NAD+, purine bases, and glycogen in biopsyspecimens of m. vastus lateralis increased. No major gender differences were observed. The tissue content of adenine and guanine nucleotides such as ATP, ADP, AMP, GTP, and GDP did not change when measured within 6 h after a 15-, 25-, or 42-km contest. During 9 days after the 42-km contest the muscle content of the adenine nucleotides showed a slight, but significant decrease. Glycogen levels were found to be decreased to 90%, 60%, and 62% of their pre-contest values after the 15-, 25-, and 42-km contests, respectively. Nine days after the expenditures supranormal levels were only measured following the 15-km contest. The tissue content of glycogen returned to pre-contest levels after the 25- and 42-km races. The present findings indicate that, from a biochemical point of view, expenditures such as 15-, 25-, and 42-km contests are very well tolerated by the m. vastus lateralis in recreative runners subjected to a training with a maximal duration of 18-20 months. PMID- 2599733 TI - Muscle carnitine level in endurance training and running a marathon. AB - Twenty sedentary volunteers (13 men and 7 women) who were subjected to an 18- to 20-month training program aimed at completing a marathon after the onset of training participated in this study. In the course of the training and after running a marathon, the content of total carnitine in the m. vastus lateralis did not change. The content of muscle total carnitine was not sex related. However, significant correlations were demonstrated between muscle total carnitine content and plasma urea and creatinine concentrations. Also a negative significant correlation was found between the content of muscle total carnitine and the plasma activity of CK before running a marathon. PMID- 2599734 TI - Structural and ultrastructural changes in skeletal muscle associated with long distance training and running. AB - The histological and ultrastructural features of 21 males and 8 females were monitored during an 18- to 20-month training period, during which the training distance was gradually increased. The training period was divided into three periods of 6, 5, and 7 months, respectively. The first, second, and third periods were concluded with a 15-, 25-, 42-km road race, respectively. The competitive distance always exceeded the maximal distance covered in any previous training session. Percutaneous biopsies were taken from the vastus lateralis muscle 5 days before each contest as well as 0.5-6 h post-contest and 8-9 days post-contest. No shift in fiber type was observed during the training period from the 15-km contest until the 42-km contest nor were any changes in fiber diameter observed. Histological examination demonstrated a gradual increase in degenerative changes during the training period, which occurred in type I as well as in type II fibers. Ultrastructural examination revealed irregular Z-lines and hypercontraction immediately after exercise. No damage to the sarcolemma was detected. The number of degenerative changes after each contest was not higher than before each race. It is concluded that long-distance running is associated with transient minor pathological changes in skeletal muscle, which are related to the total distance covered per week rather than the intensity of the exercise. PMID- 2599735 TI - Plasma activity of muscle enzymes: quantification of skeletal muscle damage and relationship with metabolic variables. AB - One hundred fourteen sedentary volunteers (34 +/- 8 years) took part in an endurance training study to be completed after 18-20 months with a marathon. Ultimately, 60 males and 18 females achieved that goal. The training program, carefully supervised, was divided into three periods with a maximum of 45-, 70-, and 110-km week training volume and concluded with a performance race of 15, 25, and 42.2 km, respectively. Three days before and 3 and 5 days after each race, 35 subjects were selected to perform a progressive treadmill test and the remaining subjects participated in field tests of 400 and 1000 m. A significant decrease in half-life time of CK enzyme plasma activity after running long distances in the course of the study from 20 h to 13 h was observed. Based on plasma enzyme activity and supposing that the total enzyme content left the muscle fiber, the estimated amount of muscle damage was found to be small. A gender difference in plasma enzyme activity increase (females demonstrated a lower increase) occurred only after the marathon. PMID- 2599736 TI - Effect of training on red blood cell parameters and plasma ferritin: a transverse and a longitudinal approach. AB - In the present study 60 males and 18 females were monitored during an 18- to 20 month training period, during which the training distance was gradually increased. The training period was divided into three periods of 6, 5, and 7 months, respectively. The first, second, and third periods were concluded with a 15-, 25-, and 42-km road race, respectively. The competitive distance always exceeded the maximal distance covered in any previous training session. The effect of training was investigated for erythrocyte count, hematocrit (Ht), hemoglobin (Hb), mean cell volume (MCV), mean cell hemoglobin (MCH), mean cellular hemoglobin content (MCHC), the red cell distribution width (RDW), and ferritin content. The measuring points were the start of the study (used as a reference value) and 1 week before and 1 week after the three contests (15, 25, and 42 km). The results of all measuring points were compared transversely and longitudinally. We found a significant decrease of plasma ferritin content in the first period of the study which further remained constant. Also, other red cell parameters were decreased but remained within the normal range. During the whole training period larger intraindividual variations for most of the red cell parameters were observed compared with non-endurance-trained people. PMID- 2599738 TI - Platelet system changes associated with a training period of 18-20 months: a transverse and a longitudinal approach. AB - The effect of training for a 42-km run was investigated for the platelet count, the platelet distribution width (PDW), the mean platelet volume (MPV), and the plateletcrit (PCT). The measuring points were the start and 1 week before and 1 week after each contest (15, 25, and 42 km). For the starting position we reassessed the reference value for each platelet parameter. The results of all measuring points were compared transversely and longitudinally. As a result of the transverse approach, we found a significant decrease of the platelet count and of the MPV, which means a decrease of total thrombocytic clotting capacity with increasing training intensity. The longitudinal approach showed large intraindividual variations for all platelet parameters during the course of the study, expressed as high values for Nvar and CVp90. PMID- 2599737 TI - White cell system changes associated with a training period of 18-20 months: a transverse and a longitudinal approach. AB - In the present study 60 males and 18 females were monitored during an 18- to 20 month training period, during which the training distance was gradually increased. The training period was divided into three periods of 6, 5, and 7 months, respectively. The first, second, and third periods were concluded with a 15-, 25-, and 42-km road race, respectively. The competitive distance always exceeded the maximal distance covered in any previous training session. The effect of training was investigated for the number of leukocytes, number of the subpopulations, and the percentage of white cells with a higher peroxidase activity (HPX cells). The measuring points were the start of the study (used as a reference value) and 1 week before and 1 week after three contests (15, 25, and 42 km). The results of all measuring points were compared transversely and longitudinally. Transversely the leukocytes hardly changed in the course of the study both in males and females, except a decrease of HPX cells. Longitudinally it appeared that Nvar and CVp90 of the numbers of leukocytes could not be calculated in males or in females. These findings suggest that a homogeneous population of leukocytes developed with respect to number and age. PMID- 2599739 TI - Occurrence of running injuries in adults following a supervised training program. AB - To study the occurrence of running-related injuries, a group of 115 volunteers were supervised in a training program. These subjects who had limited or no running experience were asked to keep a diary in which they registered information on the training program and injuries. Ultimately, 63% of the diaries fulfilled the criteria for inclusion into longitudinal analysis. The training program (18-20 months) consisted of three phases, each phase finished with a contest (15 km, 25 km, and a marathon, respectively). The participants were individually supervised by an experienced coach with special attention to physiologic training and injury-preventive aspects. Eighty-five percent (n = 62) of the research population sustained at least one injury during the experiment. They reported in total 174 injuries. The number of injury cases per week increased gradually over the experimental period; however, when expressed per unit of exposure time (i.e., 1000 training hours), it showed a decline. There was a significant correlation between the number of injured volunteers and the distance covered during the training at the start of the training program. The anatomic distribution of the injuries is in agreement with findings in the literature. There was also a possible preference for the localization of injuries to the lower leg and Achilles tendon on the left side of the body. PMID- 2599740 TI - The role of time and size in ontogenetic allometry: II. An empirical study of human growth. AB - The changes in shape that occur as a consequence of size changes during the third trimester (22 to 36 weeks post conception) of human growth are examined for muscular, tendinous and skeletal measurements of the lower limb. Gestational age and weight were highly correlated, but not linear. Several models appear to have equivalent fits to these data. The skeletal measurements were linear with body weight, but did not follow the predictions of any biomechanical model. Femur length grows more quickly than body weight, as does femur diameter. The ratio of length to diameter is nearly one, suggesting that the relative shape of the femur does not change with weight. The weights of the two muscles examined were nonlinear as functions of age or weight; Gompertz models with different coefficients fits these data best. The lengths of the two tendons were linear with age, but tendon weights were best described by nonlinear Gompertz models. One difficulty of the Gompertz models stems from the lack of an upper asymptote in these data. The data fit the lower half of the curve, however the model predicts an asymptote beyond the range of data available. The relative patterns of growth, i.e. muscles growing faster than tendons, suggest hypotheses that need to be tested with a larger data set. These include growth of muscles relative to bones or tendons in other regions, e.g., the upper limb or the cranium, and an extension of the data in time. PMID- 2599741 TI - Age-related changes in lipid peroxidation and protective enzymes in the central nervous system. AB - Brain homogenates were used to measure in vitro formation of thiobarbituric acid reactive substances (TBARS) in 5 CNS regions of 3, 12 and 22 month old male Fischer 344 rats. Glutathione peroxidase, catalase and superoxide dismutase activity in 105,000 x g supernatants of these homogenates was also measured. Results indicated that in vitro TBARS formation declined with age in all 5 areas studied. Glutathione peroxidase, catalase and superoxide dismutase activity did not change with age. Regional differences in the activity of glutathione peroxidase and catalase were noted. PMID- 2599742 TI - Heme overload inhibits the growth of normal rats. AB - We have developed a model with which to evaluate the direct metabolic effect of circulating heme in chronic hemolytic diseases. Normal rats were injected with heme intraperitoneally (IP) using different treatment schedules and then killed so their growth parameters could be measured; heme injections were well tolerated, but final body weight was decreased in the heme treated groups. In one experiment, we used heme 40 mg/kg IP 2x/d for 8 d and found that overall growth was significantly inhibited (weight increment in the heme-treated group +45 +/- 3g vs +65 +/- 3g in the controls, P less than .05); although serum somatomedin activity was significantly diminished, the liver extract somatomedin activity was not decreased. In another experiment, we compared the effect of heme 40 mg/kg versus heme 80 mg/kg IP 2x/d for 5 d: growth inhibition was dose-dependent (weight change +31 +/- 2g for vehicle-treated group versus +12 +/- 3 grams for heme 40 mg/kg group versus -6 +/- 5 grams for heme 80 mg/kg group) and related to serum heme levels (3.53 +/- 0.47 mcM for vehicle group versus 5.42 +/- 0.71 mcM for heme 40 mg/kg versus 10.91 +/- 0.84 mcM for heme 80 mg/kg group). Our data demonstrate that IP heme administration is feasible and provides a valid approach with which to identify the potential direct metabolic consequences of abnormally circulating heme and its contribution to the growth retardation associated with chronic hemolytic diseases. PMID- 2599743 TI - Growth of fetuses of rats exposed to ethanol and cigarette smoke during gestation. AB - Pregnant rats were exposed to cigarette smoke and ethanol separately and in combination in order to determine the interactive effects of these two drugs on outcome of pregnancy. The animals were exposed to cigarette smoke daily for a 2 hour period from day 1 to 20 of pregnancy. The ethanol was given in the drinking water in progressively higher concentrations. It was 10% for the first week and 20% during the next three weeks before mating, and 30% from day 1 to 20 of pregnancy. Exposure to cigarette smoke alone significantly reduced fetal weight when compared to pair-fed and ad libitum controls. The combination of ethanol plus smoke caused a significantly greater reduction in fetal weight than did ethanol alone. These findings indicate that prenatal exposure to the combination of alcohol and cigarette smoke exerts a synergistic rather than an additive effect on fetal growth. PMID- 2599744 TI - Thyroid hormones and growth patterns of embryonic and posthatch chickens from lines selected for high and low juvenile body weight. AB - Lines of chickens divergently selected for high (HW) or low (LW) 56-day posthatch body weight were evaluated for growth, development of small intestine, liver and pectoral muscle, and plasma T3 and T4 concentrations. Measurements were taken at 11,17, and 20 days of incubation and 5, 12, 20, 31, and 61 days posthatch. HW chicks and their organs were consistently larger than LW chicks and their organs from day 17 of incubation onward, and followed growth patterns characteristic of these lines. Significant line by age interactions indicated that chickens divergently selected for juvenile body weight had different temporal patterns for plasma T3 and for T4 from 11 days of incubation to 61 days posthatch. There were no differences between males and females within each line for either T3 or T4. There were no simple relationships between the patterns of plasma concentrations of either T3 or T4 and the pattern of growth of the body or the organs studied. PMID- 2599745 TI - In ovo growth hormone alters growth and adipose tissue development of chickens. AB - The effect of in ovo administration of ovine growth hormone (oGH) on growth and adipose tissue development of chickens was investigated. Unlike mammalian species, exogenous growth hormone has not been previously shown to increase growth of aves. In trial 1, fertilized eggs were injected with vehicle (.03 M NaHCO3 in .15 M NaCl, pH 8.3), 0.25, 2.5, 25 or 250 micrograms oGH on day 11 of embryogenesis. In trial 2, fertile eggs were injected with vehicle or 250 micrograms oGH. In contrast to previous studies in which GH was administered to growing birds, oGH injected in ovo in the present study increased body weights, skeletal growth and feed efficiencies of male broilers. Growth rate was not altered in females. Adipose cellularity data from both trials indicated that in ovo oGH also altered adipose tissue development of broilers. Seven-week-old male and female broilers treated with oGH during embryogenesis exhibited larger adipocytes with correspondingly less cell per gram of tissue. Additionally, adipocytes from oGH-treated broilers exhibited decreased sensitivity to glucagon, cholera toxin or theophylline-induced lipolysis responsiveness to dcAMP in ovo. Cholera toxin plus theophylline improved the lipolytic response of oGH-treated birds; thus, in broilers injected with oGH cAMP-mediated lipase activation may be reduced by a mechanism of increased phosphodiesterase activity. The results of this study indicate that growth and tissue development of chickens have been altered by mammalian GH in ovo. PMID- 2599746 TI - The impact of deinstitutionalization on the current treatment of the mentally ill. PMID- 2599747 TI - The effect of co-occurring disorders on criminal careers: interaction of antisocial personality, alcoholism, and drug disorders. PMID- 2599748 TI - The assessment, treatment and community outcome of insanity acquittees: forensic history and response to treatment. PMID- 2599750 TI - The post-assessment careers of mentally disordered offenders. PMID- 2599749 TI - The perceptions of correctional officers toward mentally disordered offenders. PMID- 2599751 TI - Chronically mentally ill inmates: the wrong concept for the right services. PMID- 2599752 TI - A demonstration program for chronic recidivists of criminal justice, health, and social service agencies. PMID- 2599754 TI - Mental disorder and the criminal justice system. PMID- 2599753 TI - Mental disorder and the criminal justice system: some overarching issues. PMID- 2599755 TI - Solubility of peptides in trichloroacetic acid (TCA) solutions. Hypothesis on the precipitation mechanism. AB - The assessment of proteolysis levels is often achieved by global quantification of the peptides soluble at different TCA concentrations, but little information is available on the features of this precipitation mechanism. Peptic, tryptic and chymotryptic digests of alpha s1, beta, and kappa caseins have been prepared and fractionated by RP-HPLC and each isolated peptide was identified. Each digest was precipitated by adding TCA to different final concentrations (2, 4, 8, and 12%). The soluble fraction was analysed by RP-HPLC. Relationships have been searched between the properties of 75 peptides obtained in this way, and their solubilities in TCA. The best correlation was found with the peptide retention time in RP-HPLC, which can be regarded as the experimental measure of peptide hydrophobicity. We concluded that TCA, by interacting with peptides, induces an increase of the hydrophobicity of peptides which can lead to aggregation through hydrophobic interactions. PMID- 2599756 TI - Regularities in the primary structure of proteins. AB - In this paper the latest protein database consisting of more than a million amino acids is analyzed to characterize the short range regularities in the primary structure. The amino acid distributions along the polypeptide chain and among the proteins have been studied first. Their influence on the amino acid pair statistics was taken into account. We are primarily interested in the distances of the covalent structure, where the amino acid pair frequencies show non-random characters. The amino acid pairs separated by at least 20 residues in the covalent structure exhibit an exact Gaussian distribution. We found that there is a range of non-random pairing in the covalent structure. We conclude that the pair preference characters are different for each of the 20 x 20 amino acid pairs. The range of the non-random pairing varies from pair to pair, and in most cases it does not extend beyond the 9th neighbour. The preferences of a certain pair in a certain position can not be derived from the character of that pair in another position. The preference values of 400 amino acid pairs are listed for up to the pairs in 9th neighbour position. Some fields of potential application of these data have also been discussed. PMID- 2599757 TI - Isolation, sequence, and conformation of seven trichorzianines B from Trichoderma harzianum. AB - From the antagonistic fungus Trichoderma harzianum, a group of acidic new peptides, trichorzianines B (TB), was isolated in addition to neutral trichorzianines A (TA) previously studied. TA and TB exhibit various biological activities related to their membrane properties and a different behaviour of the two groups was noticed. As observed for other peptaibols, TB consist in a microheterogeneous mixture which was resolved into pure peptides by reversed phase C18 HPLC. The sequence of the seven main isolated TB, namely TB IIa, TB IIIc, TB IVb, TB Vb, TB VIa, TB VIb, TB VII, was determined by the combined use of positive ion FAB mass spectrometry and 2D 1H n.m.r. spectroscopy, including COSY and NOESY experiments. TB differ from the corresponding TA only by the replacement of Gln 18 in the TA sequence by a glutamic acid. The 1H n.m.r. data suggested that the TB are mainly organized in an alpha helix. PMID- 2599758 TI - Structure and conformation of linear peptides. XIII. Structure of L-phenylalanyl glycyl-glycine. AB - The crystal structure of a tripeptide, L-phenylalanyl-glycyl-glycine (C13H17N3O4), molecular weight = 279.3, has been determined. The crystals are orthorhombic, space group P2(1)2(1)2(1), with a = 5.462(1) A, b = 15.285(5), c = 16.056(4), Z = 4, and P (calc) = 1.384 g.cm-3. The final R-index is 0.052 for 866 reflections with sin theta/lambda less than or equal to 0.55 A-1 and I greater than 1 sigma. The molecule exists as a zwitterion, with the N-terminus protonated and the C-terminus in an ionized form. Both the peptide units are in the trans configuration and planar, though one of them shows significant deviations from planarity ([delta w[ = 5.1 degrees). The peptide backbone is folded, with the torsion angles of: psi 1 = 116.2(5) degrees, omega 1 = 178.8(4), phi 2 = 89.7(5). psi 2 = -28.9(6), omega 2 = -174.9(4), phi 3 = 134.9(5), psi 31 = 7.8(6), psi 32 = -172.6(4). The terminal glycine adopts a "D-residue" conformation. For the sidechain of phenylalanine, chi 1 = 175.5(4), chi 2 = 127.0(6). PMID- 2599759 TI - Synthesis of peptide amides by Fmoc-solid-phase peptide synthesis and acid labile anchor groups. AB - The preparation and use of new anchor groups for the synthesis of peptide amides by solid-phase peptide synthesis employing the Fmoc-method is described. Based on the structure of the 4,4'-dimethoxybenzhydryl group (Mbh) handles were developed, which could be cleaved by mild acid treatment to give carboxamides. The syntheses and application of Fmoc-amino-acid-(4-carboxylatomethyloxyphenyl-4' methoxyphenyl) methyl amide and Fmoc-(4-carboxylatopropyloxyphenyl-4' methoxyphenyl) methyl amide are described in detail. These handles were coupled to resins and a stepwise elongation of peptide chains proceeded smoothly with N alpha-9-fluorenylmethoxycarbonyl (Fmoc) amino acid derivatives using a carbodiimide/HOBt mediated reaction. The final cleavage of side-chain protecting groups and the release of the C-terminal amide moiety was achieved by the treatment with trifluoroacetic acid, dichloromethane in the presence of scavengers. Various peptides, such as the Leu-enkephalin amide and Leu-Gly-Gly Gly-Gln-Gly-Lys-Val-Leu-Gly-NH2, which is a good substrate for F XIII, were prepared in high yields and purities. PMID- 2599760 TI - Structure-toxicity relationships in the amatoxin series. Synthesis of S deoxy[gamma(R)-hydroxy-Ile3]-amaninamide, its crystal and molecular structure and inhibitory efficiency. AB - The amatoxins, highly toxic components of Amanita mushrooms, strongly inhibit the DNA-dependent RNA polymerase II (or B) in eukaryotic cell nuclei. For optimal binding to the enzyme a gamma-hydroxyisoleucine side chain in the 3-position is important as in gamma-amanitin (compound 1), where the OH-group is bound in the [S]-configuration. Amanullin, a non-toxic component, having an oxygen-free isoleucine side chain no. 3, exhibits an inhibitory effect on RNA polymerase II about two orders of magnitude smaller than that of gamma-amanitin. An equal, relatively weak, inhibitory effect has previously been found with the synthetically obtained Ile3-analog 7. In the present paper the synthesis of an analog (2) bearing a gamma-hydroxyl group in the isoleucine side chain is described. The compound was found to have about the same inhibitory effect on RNA polymerase II from Drosophila embryos as amanullin and the Ile3-analog 7. Structure analysis by X-ray diffraction revealed that the hydroxyl group at the carbon atom of side chain-3 has the [R]-configuration, the new analog thus being deoxo[( )-hydroxy-[Ile3]-amaninamide. It follows that the [S]-configuration of this chiral center is a prerequisite to maximal toxicity. Crystallographic data demonstrating great similarity between the peptide backbones of the new analog and those of natural amatoxins are given. PMID- 2599761 TI - Conformational energy analysis of the chemotactic tripeptide formyl-Met-Leu-Phe and three analogs. AB - Conformational energy analyses were carried out on the chemotactic tripeptide fMLF (CHO-Met-Leu-Phe) and three analogs fALF (CHO-Ala-Leu-Phe). fMF (CHO-Met Phe), and MLF (H-Met-Leu-Phe). A near-folded or puckered conformation predominates in all four peptides. The calculated average end-to-end distance R of each of the peptides is 7.4 A, 7.6 A, 7.0 A, and 7.3 A, respectively (where bends have R less than or equal to 7 A and extended structures have R approximately 10.5 A). The puckered conformation calculated for fMLF is similar to that determined experimentally for fMLF in nonpolar solvents and in the protein receptor. The results suggest that maximum chemotactic activity of the peptides depends on a combination of the chemical structure (the presence of N formyl-methionine) and backbone conformation (C7conformation of the first amino acid residue). PMID- 2599762 TI - Synthesis of a biotinylated, iodinatable, and photoactivatable probe for angiotensin receptors. AB - We propose here a biotinyl-aminohexanoyl-[Ala1, Phe(4N3)8]angiotensin II analog as a radioiodinatable and photoactivatable probe for covalent labeling, detection and isolation of angiotensin receptors. A combination of solid phase and minimum protection segment-coupling strategy using hexafluorophosphate of (benzotriazol-1 yloxy)tris(dimethylamino)phosphonium (BOP) as a coupling reagent is proposed for the synthesis of this probe. Optimized yields were obtained by HPLC monitoring of all reactions. A complete n.m.r. study suggests an extended conformation of this molecule, allowing a simultaneous recognition of receptor and avidin. The probe binds with high affinity (Kd = 2 nM) to angiotensin II receptors from rat liver membranes. PMID- 2599763 TI - Amino acid sequence of a neutral phospholipase A2 (III) in the venom of Bungarus fasciatus. AB - Two phospholipases were found in the venom of Bungarus fasciatus, one in fraction III, the other in fraction X of the chromatographic separation. A neutral PLA2(III) purified from fraction III was subjected to amino acid sequencing by means of an automated sequenator applied to the intact RCM-PLA2 (III) and the individual peptides obtained from HPLC separation of the three types of enzymatic peptides. PLA(III) was shown to consist of 118 amino acid residues with 14 half cystines. It is 65% homologous to the basic PLA2 obtained from fraction X. PMID- 2599764 TI - Synthesis and application of acid labile anchor groups for the synthesis of peptide amides by Fmoc-solid-phase peptide synthesis. AB - The preparation and application of a new linker for the synthesis of peptide amides using a modified Fmoc-method is described. The new anchor group was developed based on our experience with 4,4'-dimethoxybenzhydryl (Mbh)-protecting group for amides. Lability towards acid treatment was increased dramatically and results in an easy cleavage procedure for the preparation of peptide amides. The synthesis of N-9-fluorenylmethoxycarbonyl- ([5-carboxylatoethyl-2.4 dimethoxyphenyl)- 4'-methoxyphenyl]-methylamin is reported in detail. This linker was coupled to a commercially available aminomethyl polystyrene resin. Peptide synthesis proceeded smoothly using HOOBt esters of Fmoc-amino acids. Release of the peptide amide and final cleavage of the side chain protecting groups was accomplished by treatment with trifluoroacetic acid-dichloromethane mixtures in the presence of scavengers. The synthesis of peptide amides such as LHRH and C terminal hexapeptide of secretin are given as examples. PMID- 2599765 TI - 1H n.m.r. conformational studies on the C-terminal octapeptide of oxyntomodulin, a beta-turn locked by a salt bridge. AB - The octapeptide Lys-Arg-Asn-Lys-Asn-Asn-Ile-Ala (Arg4 in the human sequence) is the C-terminal part of porcine oxyntomodulin, an endogeneous peptide which is a potent inhibitor of stimulated acid secretion. This octapeptide exhibits the whole range of biological activities of the parent hormone. In the present work we report an 1H n.m.r. investigation of the conformational properties of the octapeptides of pig and human sequences in dimethylsulfoxide-d6 (DMSO) solution. The various resonances were assigned on the basis of two-dimensional COSY and NOESY experiments. Other experiments such as (i) temperature and concentration dependence of the amide proton chemical shifts, (ii) effects of ionic strength, (iii) comparison of the spectra with different analogues, were performed. We showed that in DMSO, the conformation of the octapeptide is directly related to the ionisation state of the C-terminus carboxyl group of alanine. In carboxylic state, the peptide adopts an extended conformation, while in the carboxylate state the four last residues (Asn-Asn-Ile-Ala) are involved in a type II beta turn structure probably locked by a salt bridge between the carboxyl group of Ala8 and the epsilon ammonium group of Lys4 (or the guanidinium group of Arg4). These observations provide an insight into the possible conformational tendencies of this peptide in biological media. PMID- 2599766 TI - A common cytolytic region in myotoxins, hemolysins, cardiotoxins and antibacterial peptides. AB - Several proteins and polypeptides of reptilian, amphibian, insect, and microbial origin share a common cytolytic property. However, these cytolysins fulfill different objectives. They provide offensive armament in the case of toxins, but defensive systems in the case of antibacterial peptides. The sequences of several nonenzymatic cytolysins and their analogues were compared to identify the structural requirements for cytolytic activity. These cytolysins, although isolated from phylogenetically unrelated organisms, possess the common sequence features of a cationic site flanked by a hydrophobic surface. The presence of such a region apparently confers the cytolytic activity of various cytolysins. The concept of a cytolytic region is strongly supported by the existence of several natural and synthetic analogues of cytolysins and by chemical modification studies of these cytolysins. This prediction provides a new focus for cytolysin research. The understanding of this structure-function relationship should facilitate the design, synthesis, and development of better antibacterial and anticancer peptides. PMID- 2599767 TI - Asparagine coupling in Fmoc solid phase peptide synthesis. AB - To investigate side reactions during the activation of side chain unprotected asparagine in Fmoc-solid phase peptide synthesis the peptide Met-Lys-Asn-Val-Pro Glu-Pro-Ser was synthesized using different coupling conditions for introduction of the asparagine residue. Asparagine was activated by DCC/HOBt, BOP (Castro's reagent) or introduced as the pentafluorophenyl ester. The resulting peptide products were analyzed by HPLC, mass spectrometry and Edman degradation. In the crude products varying amounts of beta-cyano alanine were found, which had been formed by dehydration of the side chain amide during carboxyl activation of Fmoc asparagine. A homogeneous peptide was obtained by using either side chain protected asparagine derivatives with BOP mediated activation or by coupling of Fmoc-Asn-OPfp. Fmoc-Asn(Mbh)-OH and Fmoc-Asn(Tmob)-OH were coupled rapidly and without side reactions with BOP. For the side chain protected derivatives the coupling was as fast as that of other Fmoc-amino acid derivatives, whereas couplings of Fmoc-Asn-OH proceed more slowly. However, during acidolytic cleavage both protection groups, Mbh and Tmob, generate carbonium ions which readily alkylate tryptophan residues in a peptide. Tryptophan modification was examined using the model peptide Asn-Trp-Asn-Val-Pro-Glu-Pro-Ser. Alkylation could be reduced by addition of scavengers to the TFA during cleavage and side chain deprotection. A homogeneous peptide containing both, asparagine and tryptophan, was obtained only by coupling of Fmoc-Asn-OPfp. PMID- 2599768 TI - Studies on racemization associated with the use of benzotriazol-1-yl-tris (dimethylamino)phosphonium hexafluorophosphate (BOP). AB - The influence of the amount and nature of the necessary tertiary amine on racemization attending the BOP-mediated coupling of N-benzyloxycarbonylglycyl dipeptides has been examined by determining the epimeric products by high performance liquid chromatography. Racemization was encountered in all cases examined that included dichloromethane as solvent. The least racemization occurred when the base was diisopropylethylamine, the most when the base was N methylmorpholine. Excess base promoted racemization. Racemization was significantly diminished but not eliminated when 1-hydroxybenzotriazole was added to the reaction mixtures. The above results pertain to the coupling of peptide segments; they do not pertain to the coupling of N-alkoxycarbonylamino acids. PMID- 2599769 TI - 17O, 14N and 15N n.m.r. studies of the Co2+ complexes of cyclo(Pro17O-Gly15N) and cyclo(Gly17O-Pro) in aqueous solution. AB - The complexation of cyclo(Pro17O-Gly15N) and cyclo(Gly17O-Pro) with Co2+ ions has been studied by 17O, 14N and 15N n.m.r. spectroscopy in aqueous solution. 17O, 14N and 15N transverse relaxation times and chemical shifts were measured as a function of temperature. The 17O n.m.r. studies unequivocally demonstrate that the cobaltous ion binds to the peptide oxygen of both compounds. The hyperfine coupling constant and the peptide residence times were found to be A = -0.165 MHz and -0.145 MHz, tau m = 16, and 92 microseconds for cyclo(Pro17O-Gly15N) and cyclo(Gly17O-Pro), respectively. The 14N and 15N studies of labeled cyclo(Pro17O Gly15N) do not indicate binding at either the Gly15N or the Pro14N site. PMID- 2599771 TI - 3-Amino-2-piperidinone-6-carboxylic acid. Molecular structures of cis and trans benzoyl derivatives. AB - The cis (2a) and trans (2b) isomers of methyl 3-benzamido-2-piperidinone-6 carboxylate (Apca) were prepared and separated by fractional recrystallizations. Proton n.m.r. studies in dimethylsulfoxide solution indicate that the six membered lactam ring adopts a distorted chair conformation with an equatorially oriented benzamido substituent in both 2a and 2b. The carboxyl function also is equatorially oriented in the trans isomer 2b, but is disposed axially in the cis isomer 2a. In the crystal structure, the six-membered lactam ring of 2a is clearly in a boat conformation with the benzamido and carboxyl functions attached to the two apex carbon atoms equatorially. The trans isomer, 2b, exists as two crystallographically independent, conformationally distinct molecules in one unit cell. The lactam ring in both molecules adopts a distorted chair conformation, as is the case in solution, with both the benazamido and carboxyl functions attached equatorially. The rotameric orientation for the endocyclic lactam differs between the two molecules. Both structures show evidence of C-H...O hydrogen bond formation intermolecularly in the solid state. This ability, along with the distinctive conformational features of Apca, may be exploitable in the design of unique features of polypeptides. PMID- 2599770 TI - Interaction of gossypol with amino acids and peptides as a model of enzyme inhibition. AB - In order to clarify the interaction of gossypol with proteins, the pure diastereoisomeric Schiff bases from L-tryptophan methyl ester and both gossypol enantiomers were prepared. Their c.d. and n.m.r. spectra demonstrate that the interaction between gossypol and tryptophan, previously reported to involve a weakly associated complex, consists in Schiff base formation. Recent studies on enzyme inhibition by gossypol are discussed; it is suggested that nonspecific covalent binding of gossypol to proteins may be responsible for a significant proportion of the in vitro effects of gossypol. PMID- 2599772 TI - Structure and conformation of peptides containing the sulphonamide junction. I. N acetyl-tauryl-L-phenylalanine methyl ester. AB - N-acetyl-tauryl-L-phenylalanine methyl ester 1 has been synthesized. The crystal structure and molecular conformation of 1 have been determined. Crystals are monoclinic, space group P2(1) with a = 5.088(2), b = 17.112(17), c = 9.581(6) A, beta = 92.34(4) degrees, Z = 2. The structure has been solved by direct methods and refined to R = 0.043 for 2279 reflections with I greater than 1.5 sigma(I). The sulphonamide junction maintains the peptide backbone folded with Tau and Phe C alpha atoms in a cisoidal arrangement, the torsion angle around the S-N bond being 65.4 degrees. In this conformation the p-orbital of the sulphonamide nitrogen lies in the region of the plane bisecting the O-S-O angle, thus favouring d pi-p pi interactions between nitrogen and sulphur atoms. The S-N bond with a length of 1.618 A has significant pi-bond character. The CO-NH is planar and adopts trans conformation. The Tau residue is extended with the Tau-C1 alpha Ca beta bond anti-periplanar to the S-N bond. The Phe side chain conformation corresponds to the statistically most favoured g- rotamer and exhibits a chi 1 torsion angle of -67.5 degrees. The packing is characterized by intermolecular H bonds which the Tau and Phe NH groups form with the acetyl carbonyl and one of the two sulphonamide oxygens, respectively. PMID- 2599773 TI - Correlation of beta-bend conformations of tetrapeptides with their activities in CD4-receptor binding assays. AB - Conformational analysis, based on ECEPP (Empirical Conformational Energy Program for Peptides) using the chain build-up procedure, was applied to determine the low-energy conformations for a series of tetrapeptides. The tetrapeptides are components of larger peptides which have been found to bind to the CD4 receptor of monocytes. Several previous studies have implicated the tetrapeptide units investigated here as being critical to the biological activities of the full peptides. Five such tetrapeptides were studied: Ser-Ser-Asn-Tyr (from ribonuclease A), Thr-Thr-Asn-Tyr (from peptide T, known to block human immunodeficiency virus from attaching to CD4+ T cells), Thr-Ile-Asn-Tyr (from polio virus coat protein, which is less active than the other peptides in binding to CD4 receptors), Ser-Ser-Ala-Tyr (from the gp 120 coat protein of human immunodeficiency virus, a variant of the peptide T sequence, active in blocking viral attachment to CD4+ cells), and the tetrapeptide from an active synthetic pentapeptide, Asn-Thr-Lys-Tyr (from Asn-Thr-Lys-Tyr-Thr). Using a 7 kcal/mol cutoff, the low-energy conformations for each peptide were computed. Approximately 20,000 conformations were computed for each tetrapeptide. Residue probability profiles were determined for each tetrapeptide. All tetrapeptides except for the polio sequence showed flexibility in the sense that many low energy conformations were possible. In previous studies, it was postulated that the critical tetrapeptide units would adopt conformations similar to the one observed in a segment of ribonuclease A, residues 22-25, a beta-bend, which is part of an octapeptide segment (residues 19-26) that is homologous to the sequence of peptide T.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2599774 TI - Stoichiometry of slow binding of palmitoyl-CoA to liver glucokinase. AB - The interaction of palmitoyl-CoA with porcine glucokinase was studied by the gel permeation technique. The finding that glucokinase "bound" up to 60 molecules was unexpected from the specific inhibition of rat glucokinase by long chain acyl-CoA (Tippett & Neet, J. Biol. Chem. (1982) 287, 12839-12845). Sephacryl S-200 gel filtration in the presence of palmitoyl-CoA demonstrated a protein peak without enzyme activity that was eluted earlier than the active enzyme peak, indicating a large molecular weight shift for the inactivated enzyme form and confirming a large number (greater than or equal to 30) of associated palmitoyl-CoA molecules. The binding was also verified by analyzing the absorption characteristics of the inactivated enzyme peak. In the presence of glycerol, the size of the inactivated peak greatly decreased, but the separation between the two peaks remained unchanged. Therefore, the amphiphile bound predominantly to the inactive enzyme and not to the active form, suggesting that the rapid inhibitory interactions between palmitoyl-CoA and glucokinase previously observed are specific. Parallel enzyme activity studies showed that in the time range of the column experiments (4-20 h), both the rat and pig enzyme were greatly inactivated (greater than 90%) in the presence of palmitoyl-CoA (15 microM) in the absence of glycerol. This slow inactivation is different from the immediate specific inhibition previously reported and depends on both enzyme and palmitoyl-CoA concentrations. The presence of up to 20% glycerol slowed this inactivation process. These results demonstrated that even below the critical micelle concentration, partial inactivation of glucokinase occurs in the presence of palmitoyl-CoA over a long period of time. PMID- 2599777 TI - Orofacial myofunctional therapy for adult patients. PMID- 2599776 TI - Posterior rhinomanometric evaluation of surgical treatment for nasal airway interference. PMID- 2599775 TI - Synthesis and acid ionization constants of cyclic cystine peptides H-Cys-(Gly)n Cys-OH (n = 0-4). AB - Cyclic peptide disulfides of the general formula H-Cys-(Gly)n-Cys-OH (n = 0-4) were synthesized from the corresponding peptide derivatives [Boc-Cys(Trt)(Gly)-n Cys(Trt)-OBut] by oxidation with iodine in methanol and by subsequent removal of the terminal groups with trifluoroacetic acid. Acid ionization constants of the obtained peptides were determined by potentiometric titration in aqueous KCl (0.1 mol/L) medium. All compounds have two dissociable hydrogens, corresponding to carboxyl (pK1 = 2.35-2.84) and to terminal amino group (pK2 = 5.61-6.93); pK1 values show first an upward and then a downward trend with the increase in ring size; the opposite is true for pK2 values. These trends could be tentatively attributed to the intramolecular salt bridge (-COO- ----NH+3-) formation. PMID- 2599778 TI - Evaluation of palatal depth and width in mouth breathers with primary dentition. PMID- 2599779 TI - Orofacial myofunctional therapy for bilateral tongue posture and tongue thrust associated with open bite: a case report. PMID- 2599780 TI - The immediate placement of an endosseous implant into an extraction wound: a clinical case report using the RosTR System. PMID- 2599781 TI - Restoration of endodontically treated teeth with interradicular lesions before root removal and/or root separation. PMID- 2599782 TI - New attachment following the use of a resorbable membrane in the treatment of periodontitis in dogs. PMID- 2599783 TI - The effects of electrode placement upon EEG biofeedback training: the monopolar bipolar controversy. AB - Roles of tradition, convenience, and noise or artifact rejection are discussed with regard to the monopolar versus bipolar electrode placement controversy in electroencephalography (EEG). Particular emphasis is placed on the relevance to biofeedback. The crucial interactions between the differential amplifier, brain waves, and monopolar/bipolar placements are discussed. Through logical analysis and empirical observation, it is demonstrated how the very nature of the EEG's differential amplifiers must destroy those elements of brain activity which are common to the recording electrodes. Controlled experiments further illustrate the critical importance of electrode placements. Various methods, including preferred electrode placements, are presented to help resolve recording problems that frequently arise. It is concluded that there are serious implications for researchers, EEG clinicians, biofeedback providers, and their clients in preferring one type of electrode placement technique over the other. EEG recording accuracy is affected by this choice. PMID- 2599784 TI - Sensibility threshold, mental health, and endocrine markers in patients with chronic orofacial pain. AB - Sensibility threshold, mental health, and plasma beta-endorphin, cortisol, and prolactin levels were studied in 15 patients suffering from chronic orofacial pain or discomfort, six of them with oral lichen planus and nine with atypical facial pain. Five patients were used as controls. The results showed a difference in mental health and sensibility threshold; the mentally more disturbed had a lower sensibility threshold. The patients suffering from chronic pain were more frequently mentally disturbed than the patients in the control group and also had a lower sensibility threshold than the controls. Neither severity of pain nor mental disturbance correlated with the endocrine markers. PMID- 2599785 TI - Stress-related problems of dentists. AB - The dental profession is somewhat unique in that it has higher stress levels and more stress-related problems than most vocations. This has been discussed in detail, and some common sense, frank, and ethical recommendations, which have been clinically and personally shown to be effective, are presented to help reduce these problems. PMID- 2599786 TI - Treatment of bulimia with hypnosis involving awareness and control in clients with high dissociative capacity. AB - The details of an easily replicable intervention using hypnosis in the treatment of bulimia are presented. Follow-up data at one month, three months, six months, and one year indicated that the intervention appeared to be effective in two out of the three cases presented. Factors affecting treatment outcomes are discussed. PMID- 2599787 TI - Psychological modulation of auditory responses. AB - In a study of the cyberphysiology (self-regulation) of auditory response, the effects of imagery and suggestion on auditory thresholds were examined in naive subjects (Ss). After a hypnosis-like induction, the Ss, who were not aware of the purpose of the study, were asked to generate and maintain a specific set of images before, during, and after which their auditory thresholds were tested. The Ss were not informed of the purpose of the imagery or audiograms. Following the imagery, which represented cooling and vasoconstriction in the cochlea, audiograms revealed a temporary auditory threshold shift (TTS) in the experimental group only. This TTS response pattern was similar to that produced by exposure to loud noise. Information carried in the image is suggested as the basis for the observed auditory changes. Although a hypnosis-like induction was employed, the Ss' level of hypnotizability did not appear to be related to the findings. PMID- 2599788 TI - Stress among Israeli dental students: a two-year longitudinal study. AB - Forty Hebrew University-Hadassah dental students, graduates of one class, were followed-up over two years of study, during their fourth and fifth years of studies. Students ranked a list of potential stress sources in the dental school environment. Increases in reported stress sources were detected longitudinally for: (1) the requirement system; (2) inconsistent feedback; (3) lack of free time; and (4) treating children. Decreases in reported stressors were found for: (1) manual dexterity; (2) covering the study material; and (3) understanding material. Students reported an increase in stress regarding treating adults from the fourth to the fifth year but then a decrease in stress during the fifth year. Studies have demonstrated dentists as a social group to be especially prone to the effects of stress. This pattern might be initiated in dental school. PMID- 2599789 TI - A pilot study of a modified Balint group using cognitive approaches to physician attitudes about somatoform disorder patients. AB - This is a pilot study of the use of cognitive therapy theories and techniques in a time-limited Balint group of family physicians with a focus on the care of the somatoform disorders. Family physicians often find these patients difficult and unpleasant to treat. Physicians in the group were compared with other family physicians in a pre and post test of attitudes towards patients with somatoform disorders. In addition, the beliefs of the physicians were elicited. After the 13 session Balint group was completed, attitudes of the family physicians in the group improved so that they were less likely to feel that somatizing patients take up too much of their time (p less than 0.05). Underlying beliefs about somatoform disorder patients were identified in the group and subsequently modified. This study suggests that a time-limited cognitive therapy Balint group, focusing on somatoform disorder patients, results in improved attitudes toward the care of these patients. PMID- 2599790 TI - Hypnosis techniques. AB - These are simple techniques used to: (1) guide a patient into a trance; (2) teach auto-hypnosis; and (3) utilize the techniques of Elizabeth Kubler-Ross and Carl Simonton. PMID- 2599791 TI - Plasma vitamin A composition and retinol-binding protein concentration during egg formation in laying hens. AB - Blood plasma vitamin A composition (retinol, retinyl ester) and retinol-binding protein (RBP) were determined in three phases (empty; soft- and hard egg) of the egg formation period in laying hens. The retinyl ester level remained in the range of 6 to 11% of the total plasma vitamin A concentration during egg formation. The retinol and RBP increased significantly during the time of soft period. The molar ratio between retinol and RBP ranged between 0.72-0.77. The increase of retinol and RBP may be caused by the sexual steroid effect for satisfying the retinoid needs of the ovarium and shell gland (avian uterus). PMID- 2599792 TI - Plasma tocopherol and tocopherol to lipid ratios in a normal population of infants and children. AB - The plasma tocopherol concentrations were measured by HPLC in 73 apparently healthy West German children aged from 1 to 14 years and in 7 cord blood samples and 5 infants below 1 year of age. Total tocopherols ranged from 584 to 2024 micrograms/dl in the children above 1 year of age (mean 1046 +/- 283 micrograms/dl) and from 511 to 1155 micrograms/dl in the infants below 1 year of age (mean 879 +/- 270 micrograms/dl). The total tocopherol/total lipid ratio representing the reliable index for vitamin E status-was far above 0.6 mg/g lipid, a level which is regarded as the lower limit of normal (range 1.23 to 4.09 mg/g total lipid in the older children and 1.52 to 2.05 in the infants below 1 year). A positive correlation was found between plasma lipids and total tocopherol (r = 0.71). Our investigation demonstrated an excellent vitamin E status in the children investigated which is considered to reflect the high supply of West German food with PUFA and vitamin E. PMID- 2599793 TI - Protective effects of vitamin E in age-related endothelial cell injury. AB - Age is strongly correlated to the onset of atherosclerotic lesion formation in humans. This may be associated with an age-related increase in the susceptibility of the vascular endothelium to oxidative injury. Such injury may result in altered endothelial function as a barrier to plasma components, such as cholesterol-rich lipoprotein remnants. To investigate this hypothesis, the relationship between endothelial cell culture age, susceptibility to oxidative injury and protection against this injury by the nutrient/antioxidant vitamin E on endothelial barrier function (transfer of albumin across endothelial monolayers) was examined. An acute 24 h exposure to 30 microM linoleic acid hydroperoxide resulted in increased albumin transfer at all cell passages tested (up to passage 50). Pre-enrichment of cells with 25 microM vitamin E always protected endothelial cells against oxidized fatty acid-induced cell injury, independent of cell age. In comparison, patterns of total cell protein and DNA were not markedly influenced by experimental treatments, although age-related declines in total DNA were noted. These data suggest that the possible correlation between age and the onset of atherosclerosis may be in part related to a decrease in endothelial barrier function due to oxidative stress, permitting more blood components to enter the arterial wall. Furthermore, vitamin E may protect endothelial cells against oxidant-mediated vascular injury. PMID- 2599794 TI - Effect of intraperitoneally injected tocopherol on vitamin E status of dairy cow. AB - The effect of intraperitoneal (IP) administration of vitamin E on the concentration of tocopherol in the blood and milk of cows was studied. Two trials were carried out using a total of twenty-four Holstein cows. In the first trial, two doses of dl-alpha-tocopherol (1 g and 5 g) were given to six cows in each treatment. Administration of 1 g caused a small increase in blood and milk concentrations; dosing with 5 g IP caused appreciable increases in both plasma and milk concentrations. Plasma and milk concentrations peaked 1 d after dosing with a maximum value of 10.7 micrograms/ml plasma and 1.39 micrograms/ml milk. Then there was a continuous decline during the 14 d experimental period. In the 2nd trial, twelve cows were dosed IP with the acetate form of vitamin E. Six cows were given 5 g and six others 10 g of dl-alpha-tocopherol acetate. Maximum plasma vitamin E concentrations occurred at d 2 (7.4 micrograms/ml) and d 1 (10.9 micrograms/ml) for the cows dosed with 5 and 10 g of the ester form, respectively. Milk vitamin E concentrations were significantly higher (P less than .05) during the first 4 d for cows dosed with 10 compared to those given 5 g. During the 14 d experimental period, maximum milk vitamin E concentration for the 10 g group was 141 micrograms vitamin E/g fat 2 d after dosing and for the 5 g group 62 micrograms vitamin E/mg fat also at 2 d after dosing. The technique of dosing cows with vitamin E by IP proved to be an effective way for increasing vitamin E status. These treatments had no effect on cholesterol content of milk fat. However, it was noted that cholesterol level was lower in PM milking as compared to AM milking. PMID- 2599795 TI - Human serum ubiquinol-10 levels and relationship to serum lipids. AB - Serum and urinary levels of ubiquinol-10 (UQH2-10) as well as total ubiquinone-10 (total UQ-10, sum of UQH2-10 and oxidized UQ-10) were determined in healthy Japanese subjects using high performance liquid chromatography with an electrochemical detector. The mean serum and urinary levels of UQH2-10 were 0.75 +/- 0.21 microgram/ml (86% of total UQ-10, n = 77) and 0.045 +/- 0.016 microgram/mg creatinine (59% of total UQ-10, n = 30), respectively. After daily oral administration of 60 mg of UQ-10 for 7 days, the human serum level of UQH2 10 increased twice as compared to that before the treatment. However, the ratio of the UQH2-10 to the total UQ-10 remained unchanged during such administration. The serum level of UQH2-10 correlated significantly with those of vitamin E (p less than 0.001), phospholipids (p less than 0.01), total cholesterol (p less than 0.05), and total lipids (p less than 0.05). There was no correlationship between the serum levels of UQH2-10 and of triglycerides and lipid peroxides. PMID- 2599796 TI - Alteration of tissue magnesium levels in rats by dietary vitamin B6 supplementation. AB - Tissues from female Fisher rats fed varying levels of magnesium (100 ppm or 700 ppm) and pyridoxine hydrochloride (PN.HCl) (7, 35, or 1500 mg/kg diet for six weeks) were dry ashed and analyzed for magnesium using atomic absorption spectroscopy. In tissues from rats consuming magnesium diets, tissue magnesium levels increased as levels of dietary PN.HCl increased. Increases in plasma, liver, kidney, and brain magnesium levels were statistically significant (p less than 0.05). With the exception of liver, no statistically significant changes in tissue magnesium levels occurred with PN.HCl supplementation in rats fed diets with adequate magnesium. Dietary supplementation with PN.HCl produces alterations in tissue magnesium levels in the rat and these alterations are modulated by dietary magnesium and PN.HCl supplementation. PMID- 2599797 TI - Thiamin, riboflavin and pyridoxine status in chronic renal insufficiency. AB - The restricted diets of patients with chronic renal insufficiency (CRI) can lead to inadequate intake of some vitamins. We studied thiamin, riboflavin and pyridoxine nutritional status of CRI subjects on unrestricted or low-protein diet. Results show that riboflavin status is inadequate even before the beginning of the follow up and worsens with time for both groups, while thiamin and pyridoxine status becomes inadequate in some patients after a long period on the low-protein diet. Water-soluble vitamin supplements could improve the nutritional status of CRI patients on protein-restricted diet. PMID- 2599798 TI - CNR firms up nursing's stand on critical issues. AB - For the ICN, the decisions made by its governing body, the Council of National Representatives (CNR), give focus to its work programme and set policy. At the its pre-Congress meetings in Seoul at end-May, the CNR set the pace for nursing's direction by taking a stand on a variety of important issues. The subjects tackled were of significance both internationally and for ICN. The CNR passed some potentially contentious and decisive resolutions. Reasoned debate on these resolutions was followed by some tough decisions-decisions taken with confidence and the knowledge that they involved work for ICN but also for national nurses' associations. PMID- 2599799 TI - Nursing--a new tomorrow. AB - This year's recipient of the prestigious Christiane Reimann Award, the "Nobel Prize of Nursing", was Dame Nita Barrow, Ambassador to the UN from Barbados, who was recognized for her distinguished accomplishments in nursing and health care over decades and continents. She was also the keynote speaker at ICN's 19th Quadrennial Congress in Seoul, Korea, 28 May-2 June 1989, described by Korean Prime Minister Kang Young Hoon in his address at the opening ceremonies as the "festival of peace and friendship for nurses the world over". Below, her keynote address. PMID- 2599800 TI - Nursing code of ethics: an international comparison. AB - In her worldwide search for a code of ethics to provide guidelines for professional practice, Linda Sawyer found that the codes of health care professionals were disappointing, mainly because they did not provide thoughtful and provocative discussion of the bioethical issues faced by the practitioner. Many organizations deal with controversial issues through the informal mechanism of policy statements, rather than through the more formal, rigid, public and political process needed to amend a code of ethics. While other professional organizations focus on commercial aspects of practice or are silent on ethical issues. Below, an analysis of the codes of selected national nurses' associations. PMID- 2599801 TI - Genes involved in the metastatic process. PMID- 2599802 TI - Assessment of N-methylformamide (NMF) administered orally on a three times weekly schedule: a phase I study. AB - This phase I study was conducted to reevaluate the dose-limiting toxicities, maximum tolerated (MTD) and recommended phase II doses of oral NMF administered on a three times weekly schedule for 4 out of every 6 weeks. This schedule was based on the observation that prolonged administration of NMF was associated with the most efficacious antitumor activity in preclinical studies. Phase II trials that employed a starting dose of 800 mg/m2, determined in a previous phase I trial, were suspended because of frequent and severe toxicities. In the current study, a symptom complex characterized by nausea, vomiting, and malaise was the dose-limiting toxicity of oral NMF administered on this schedule. Other toxicities included hepatic enzyme elevations, mild myelosuppression, and worsening of preexistent toxic peripheral neuropathies. Of interest, three patients who were asymptomatic prior to treatment, rapidly developed symptoms of increased intracranial pressure after starting NMF; and, computerized tomographic brain scans revealed metastatic tumors with significant peritumoral edema. NMF was well tolerated at 600 mg/m2, however, an abrupt increase in toxicity resulted when the dose was increased to 700 mg/m2. Although NMF peak plasma concentrations (Cmax) and areas under the plasma disappearance curves (AUC) differed between the 600 and 700 mg/m2 dose levels, these differences were not striking, and similar NMF plasma concentrations and exposures were well tolerated during intravenous trials. Based on this study, the recommended phase II dose for oral NMF administered three times weekly for 4 of 6 weeks was 600 mg/m2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2599805 TI - Improving oral health in the elderly. PMID- 2599803 TI - A phase II clinical trial of diaziquone (AZQ) in the treatment of patients with recurrent adenocarcinoma and adenosquamous carcinoma of the cervix. A Gynecologic Oncology Group study. AB - Twenty-six patients with recurrent adenocarcinoma and adenosquamous carcinoma of the uterine cervix were treated with diaziquone (AZQ) 22.5 mg/m2 diluted in 150 ml normal saline every three weeks. In the absence of adverse effects the second dose and all subsequent doses were escalated to 30 mg/m2. All patients had measurable disease and only 11 had received prior chemotherapy. Two partial responses were noted among 15 patients with no prior chemotherapy, while no responses were observed among 11 previously treated patients. The major toxicity was leukopenia and thrombocytopenia. Median progression-free interval was 1.5 months and median survival was 4 months. AZQ displays minimal activity against recurrent nonsquamous carcinoma of the cervix at the dose and schedule used. PMID- 2599804 TI - Sixth NCI-EORTC symposium on new drugs in cancer therapy. Amsterdam, March 7-10 1989. Abstracts. PMID- 2599806 TI - Use of composite resins in posterior teeth by Iowa dentists. PMID- 2599807 TI - Prevent dental treatment from precipitating peptic ulcer disease. Part 1. PMID- 2599808 TI - What's new in otolaryngology? AB - The author discusses advances in the practice of otolaryngology, focusing on diagnosis and surgical techniques. New requirements for physicians are also discussed. PMID- 2599809 TI - Otolaryngologists stress education. AB - The author, an otolaryngologist in Ottumwa and president of the Iowa Academy of Otolaryngology, discusses that organization's goals and the current practice environment for otolaryngologists. PMID- 2599810 TI - Nasal obstruction portending nasal cavity cancer. AB - This report demonstrates why all patients presenting with persistent nasal obstruction should be completely evaluated because of the difficulty in diagnosing nasal chamber tumors. PMID- 2599812 TI - Urolithiasis: extracorporeal shock wave lithotripsy and endourologic techniques. AB - The author discusses effective treatment of stubborn kidney stones, utilizing extracorporeal shock wave lithotripsy augmented with traditional endourologic techniques. PMID- 2599811 TI - New laryngeal surgery may improve voice. AB - Laryngeal framework surgery has increased the options the otolaryngologists have available to treat voice disorders ranging from unilateral vocal cord paralysis to pitch disorders. PMID- 2599814 TI - Touching. PMID- 2599813 TI - Leadership. PMID- 2599815 TI - Record retention. PMID- 2599817 TI - Working for safer roads. PMID- 2599816 TI - Collecting vital statistics. PMID- 2599818 TI - Public health leads IMS legislative agenda. AB - Transportation safety, tobacco restriction and other vital issues such as mandatory Medicare assignment are IMS priorities for the upcoming session of the Iowa Legislature. The author, chairman of the IMS Committee on Legislation, discusses the 1990 IMS legislative agenda. PMID- 2599819 TI - Our campaign finance system: a status report. AB - For this month's special legislative issue, IOWA MEDICINE asked Elizabeth Buck, executive director of the Iowa Democratic Party, and Randy Enwright, executive director of the Republican State Central Committee, to comment on political campaign financing. Political Action Committee (PAC) contributions and their impact on candidates are discussed. PMID- 2599820 TI - Necrotizing fasciitis. AB - Early recognition of necrotizing fasciitis is the key to successful treatment. However, initial presentation of this disease is variable. In this case report, the first clinical evidence was a gram stain of the deep surface of the superficial fascia. PMID- 2599821 TI - Responding to adolescent health needs. PMID- 2599822 TI - Immunotherapy for cancer--back to the future. PMID- 2599823 TI - Farmers lung: a three year survey and comparison of ELISA and CIEP techniques in antibody detection. AB - The incidence of detection of antibodies against antigens derived from two thermophilic actinomycetes in patients clinically suspected of having Farmer's Lung was assessed. Approximately 25% of samples submitted over a three year period were found to be positive in either the ELISA test or the CIEP test for antigens derived from M. faeni and T. vulgaris. The ELISA test proved to be more sensitive than the CIEP test in the detection of antibodies directed against both organisms. PMID- 2599824 TI - The Swenson operation in the treatment of Hirschsprung's disease. AB - A review of the clinical features, postoperative course and long-term follow up of a series of 40 patients having a Swenson pull-through procedure for Hirschsprung's disease is presented. The immediate postoperative recovery and long term bowel function was generally satisfactory and compared well with other operations used in this condition. Most of the residual problems with regard to functional outcome were in the younger age group who would be expected to gain more control with time. The provision of a covering colostomy in the post operative period, improvements in chemotherapeutics and in the intensive care management of these patients in recent years are discussed with regard to the avoidance of septic complications and mortality related to the operation. PMID- 2599825 TI - An evaluation of cranial CT scanning in clinical psychiatry. AB - From 6,300 psychiatric admissions over a 37 month period, all 54 patient referrals for CT were identified and their charts reviewed. CT influenced diagnosis, management or prognosis in 11.7 percent of patients scanned. There was poor correlation between organicity on CT scan and findings on physical examination, laboratory testing, EEG and psychological testing. The mental state examination was the single significant correlate of CT abnormality. We suggest that the use of a formalised mental state examination such as the Mini Mental State, in addition to the usual clinical assessment of mental state, may improve the accuracy of prediction of abnormality on CT scan. The introduction of X-ray computed tomography (CT) is recognised to be one of the most important innovations in the recent history of clinical medicine. In neurology the value of a non-invasive technique for examining the intracranial contents was quickly realised in the areas of diagnosis, particularly in the detection of vascular accidents and tumours. CT has also attained a significant place in psychiatry. In research studies, it has provided important information on schizophrenia, alcoholism and chronic organic reactions. The place of CT in clinical psychiatry is less clear. As its availability has increased, such scans are being requested with increasing frequency in psychiatric patients. Cranial CT is a highly sensitive diagnostic procedure which, when used unselectively, may result in the discovery of incidental findings. Until recently, a function of the psychiatrist in relation to diagnosis was to first seek to distinguish symptoms produced by organic pathology from those produced by functional illness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2599827 TI - Clinical trials act and medical research. PMID- 2599826 TI - Current status of myelography in the evaluation of the thoracic spinal cord. AB - The myelographic features in 35 patients with clinical thoracic spinal cord disease and normal plain radiographs were reviewed to re-evaluate the role of pre operative myelography since the advent of computed tomography and magnetic resonance. The most frequent lesions were meningioma (9 cases), prolapsed intervertebral disc (9 cases), and metastases (8 cases). The extent and anatomical location of the lesion was demonstrated in all 19 patients without myelographic block. In 16 cases with complete block, the anatomical location was demonstrated in 14, and the extent of the lesion in four, using cervical puncture in two and CT myelography in one. Myelography remains a valuable method of assessment of the thoracic spinal cord and canal and is sufficient to allow the preoperative planning of surgical management in the absence of complete block. Additional investigation by computed tomography or magnetic resonance imaging is advised in the presence of complete block or an intramedullary lesion. PMID- 2599829 TI - Familial cancers. PMID- 2599828 TI - Childhood asthma--the Paris accord. PMID- 2599830 TI - Supervision of the fetus during labour. PMID- 2599831 TI - Small area mortality patterns. AB - Little information on the health of populations living in small geographic areas of Ireland is available and it is therefore difficult to clearly identify small communities whose health is significantly below average. The aim of this study was to identify areas within Dublin having above average death rates by application of the technique of small area analysis. By using mortality and census data and by calculating standardised mortality ratios, a number of electoral wards/district electoral divisions in Dublin with significantly elevated mortality rates from all causes and from specific disease groups were identified. In general these were in inner city areas and new suburbs to the north and west of the city. A considerable proportion of the excess mortality can be attributed to conditions amenable to preventive measures. Before specific intervention is attempted, local investigation by Directors of Community Care/Medical Officers of Health will be necessary in order to confirm the findings and to identify factors which may be amenable to prevention. If intervention is attempted it should be carefully planned and should be implemented on a pilot basis initially. PMID- 2599832 TI - Malignant melanoma lately diagnosed. AB - To assess the clinical impression that patients in Dublin were presenting with late, deep, poor prognosis lesions, a 10 year retrospective review of patients with malignant melanoma was performed. The pathological data on 186 patients was examined and clinical follow-up obtained on 151 of these (80%). The mean period of follow-up was 35 months. Females predominated in a ratio of 3:1. Incidence figures for the two five year periods (1976-80) and (1981-85) indicated a rise in the latter period of over 100%. There was a marked delay in presentation after the onset of symptoms i.e. new pigmented lesions or changes in pre-existing lesions (mean = 21 months). Only 45% of lesions were less than 1.5mm in depth. Females presented with a higher percentage of good prognosis lesions reflected in a superior five year survival figure of 70% compared with 43% for males. The results of this study suggest an increase in incidence and mortality from malignant melanoma in this country. Patients appear to be unaware of the significance of pigmented lesions, presenting late with deep poor prognosis tumours. PMID- 2599833 TI - Community notification of child sexual abuse. AB - There has been a heightened awareness of sexual abuse of children in Ireland in the past four years. One-hundred and forty seven cases of alleged sexual abuse notified to the Director of Community Care in 1986-1987 were reviewed retrospectively from the medical and social work notes. In 81 (55%) cases, sexual abuse was either confirmed or strongly suspected and these were analysed further. Victims were twice as likely to come from an urban as from a rural background. Girls were more likely to be abused at all ages, and this was particularly marked in the teenage years. Abusers were either intra-familial or known to the family in most cases. A surprising number were under 16 years of age. The study highlights the time commitment needed to manage this problem in the community and the need to develop services directed towards the young perpetrator. It also raises concern at the sizable percentage of children who, following investigation, are found not to have been abused. PMID- 2599834 TI - Serum hypomagnesaemia in an elderly day-hospital population. AB - Serum magnesium concentration was measured in 223 elderly patients attending a day-hospital. Patients with medical conditions or receiving medication (other than digoxin/diuretics) which could affect magnesium levels were strictly excluded from the study. All patients were living in the community and were medically stable. Ninety-five patients were on no therapy whilst 107 were on diuretic therapy. In spite of strict exclusion criteria, 10.3% of patients on no therapy had serum magnesium levels below normal. There were 61 patients receiving a combination of frusemide and amiloride and 11.9% of these patients had below normal levels of serum magnesium. We conclude that there is a significant prevalence of unexpected hypomagnesaemia among Dublin inner city day hospital elderly patients. Significant serum hypomagnesaemia may still occur in patients on potassium/magnesium sparing diuretics. PMID- 2599835 TI - Acute effects of the Chernobyl nuclear accident on Irish mortality? AB - This report examines the claim that Irish mortality in the second quarter (April June) of 1986 increased due to the cloud of radioactive material released by the damaged reactor in Chernobyl. Over the period 1971-1987, based on date of registration, the death rates in the second quarter showed marked year to year variation often exceeding that expected on the basis of chance alone. In 1986 the percentage of annual deaths occurring between April and June, and the death rate itself, were both significantly higher than in most other years between 1981 and 1987. The 1986 figures were not however, significantly higher than those observed in years prior to 1981. Since the distribution of mortality by cause was not consistent with the hypothesis relating low level radiation to immediate mortality, and since causality cannot be inferred from a temporal association per se, the Chernobyl accident cannot be implicated in the excess mortality observed in the second quarter of 1986. PMID- 2599836 TI - Warts in general practice. AB - Eight hundred and ninety seven patients referred by their general practitioner to Health Centre Wart Clinics were interviewed. Seventy one patients (7.9%) were found to have lesions other than cutaneous warts. Females were significantly more likely to have plantar warts on their toes (p less than 0.002) and non-plantar warts on their fingers (p less than 0.03) and less likely to have non-plantar warts on the palms of their hands (p less than 0.03) than males. Patients living in large households (5+ persons) were more likely than patients living in smaller households (2-4 persons) to report an infected co-habitant (p less than 0.001). Patients with periungual warts were significantly more likely to be nailbiters. (p less than 0.001). Patients presenting with warts greater than two years in duration were more likely to have multiple warts than those with warts less than one month in duration (p less than 0.001). Patients who frequently immersed their hands in water were more likely to present with multiple warts on the hands (p less than 0.001). Multiple plantar warts were associated with moist or macerated feet (p less than 0.001). The role of the family doctor in diagnosing and preventing the spread of this infection is discussed. PMID- 2599837 TI - Does smog increase the general practitioner's workload? AB - Dublin city experienced a week-long episode of intense smog in November 1988. A retrospective analysis was carried out in ten general practices of the numbers of patients seen during November. Each practice was situated in an area affected by high smog levels. The numbers of patients seen in surgery and on house-calls showed no differences during the weeks preceding the smog outbreak, during the period of high smog levels or during the week after this period. No qualitative data on the reasons for patients' visits were collected and no comments can be made on the nature of patients' illnesses during this period. There was no evidence for an increased workload in general practice caused by this episode of intense smog but a prospective study is necessary to confirm this finding and to examine the nature of patients' problems during such an episode. PMID- 2599838 TI - Cystic leiomyoma of the stomach. AB - Leiomyomas of the stomach are uncommon and a minority of them are malignant. The diagnosis of a pedunculated, extragastric and benign leiomyoma presenting as a cystic mass in the left upper quadrant proved difficult. The investigation and management of this condition are discussed. PMID- 2599839 TI - Retrograde ejaculation--pregnancy following artificial insemination. AB - A case of retrograde ejaculation is described where pregnancy was achieved by artificial insemination using sperm recovered from the urinary bladder. The importance of the accurate diagnosis of retrograde ejaculation and its management is discussed. PMID- 2599840 TI - Measles giant cell pneumonia in children with malignant disease: a plea for immunisation. AB - During the measles epidemic of 1982-3, three children who were treated for malignant disease developed measles giant cell pneumonia. All three patients died despite intensive therapy. As there is no effective treatment for giant cell pneumonia, measles must be eliminated by widespread immunisation. PMID- 2599841 TI - French angles: a simple aid to neurodevelopmental examination. AB - "French angles" are the amplitude of passive movement at a single joint, which can be easily measured using a goniometer, and reflect the lengthening capacity of muscles--a component of passive tone. Fifty infants aged 1-52 weeks had their "French angles" measured by non-expert examiners using a plastic goniometer. All the angles measured, except ankle dorsiflexion, increased in a predictable, linear fashion from birth to one year of age. Thus in normal term infants passive tone gradually relaxes from birth to the age of one year. Three additional infants with known neuromuscular disorders were found to have angles outside the obtained normal range. The babies with cerebral palsy had reduced adductor angles reflecting adductor spasm, and the baby with Werdnig Hoffman syndrome had an increased adductor angle reflecting increased adductor extensibility. The results provide a quantitative measurement of neurological maturation during infancy, and should complement the routine neurodevelopmental assessment. The method proved quick, simple and reliable, and may become useful as a screening test for neuromuscular disorders. PMID- 2599842 TI - Transient diabetes insipidus following listeria meningitis. AB - Disorders of ADH secretion associated with meningitis are usually consistent with the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH). This reports an unusual case of central diabetes insipidus following SIADH secondary to listeria monocytogenes meningitis in a neonate. PMID- 2599843 TI - Acquired immunodeficiency syndrome. AB - A report entitled "Kaposi's Sarcoma and Pneumocytosis Carinii Pneumonia among homosexual men in New York City and California" in the MMWR in July 1981 alerted the world to the appearance of a completely new disease. The opportunistic infections and cancers occurring in these patients had previously only been seen in patients who were immunosuppressed. Homosexual men were the first as a major risk group to be identified. Others quickly followed. The pattern of occurrence clearly indicated an infectious agent as the likely cause, and within two years the virus had been identified in Europe and the USA. In Europe it was named Lymphadenopathy Associated Virus (LAV) by Montagnier its discover, and in the USA, Human T cell Lymphotrophic Virus III (HTLV III). It is now known as Human Immunodeficiency Virus (HIV). PMID- 2599844 TI - Cerebral palsy in multiple births. PMID- 2599845 TI - Diabetic neuropathy: assessment and treatment. PMID- 2599846 TI - Post-injective quadriceps contracture. AB - After reviewing the literature, the authors report 19 patients affected with post injective contracture of the quadriceps muscle observed by them between 1971 and 1983. Clinical evaluation, indications for surgery and the results of surgery are discussed. PMID- 2599847 TI - Problems related to blocked nailing in fractures of the proximal femur. AB - The modern treatment of fractures of the proximal femur in the adult usually involves surgery. Open plating has proved to be reliable, but often involves a high percentage of complications: axial deformity, delayed union, breakage of the plate and/or screws (the risk of which increases in relation to the degree of comminution). At this site, in fact, the plate is submitted to strong flexion stress. It therefore becomes essential to associate cancellous grafts (as proposed by the AO School) (Muller et al., 1981) or a homoplastic cortical craft (as in our experience) (Zinghi and Masetti, 1982). Furthermore, open osteosynthesis is time consuming and this means considerable blood loss and a risk of infection. There are thus many reasons for preferring closed surgery, but effective stabilisation can only be obtained with blocked nailing; in fact, only metadiaphyseal screwing is capable of neutralising the rotation or axial stresses which cause deviation, instability or telescoping of the fracture (Kempf et al., 1978; Tigani et al., 1986; Zinghi et al., 1984). Osteosynthesis with Grosse-Kempf nailing is thus an effective alternative to open nailing, particularly in those fractures which would require additional bone grafting with this method. The purpose of our study was to verify the effectiveness of intramedullary osteosynthesis with Grosse-Kempf blocked nailing, in particular analysing the problems encountered in the use of this method. PMID- 2599848 TI - Osteosynthesis of the cervical spine with an anterior plate. AB - Osteosynthesis of the cervical spine with an anterior plate is indicated for reconstruction by a bone graft after somatectomy and in anterior fusion for unstable lesions such as fracture dislocations and fractures with severe deformity. In these situations traditional surgery with intersomatic wedged bone grafts may be insufficient and posterior surgery inadequate or risky. The authors report 11 cases of anterior osteosynthesis with a Louis plate, all of which were sufficiently stable to allow early mobilisation and minimal external orthosis. Fusion of the grafts occurred in all cases at long-term follow-up. The method involves a potential risk to the esophagus, which is in close contact with the plate. It must therefore be limited to cases in which the advantages outweigh the risks. The indications, technique, complications and results are discussed. PMID- 2599849 TI - Resection of the radial capitellum. Long-term results. AB - The results of 39 resections of the radial capitellum reviewed after an average of 12 years were excellent or good in 59% of the cases and fair or poor in 41%. The results were better in isolated fractures of the capitellum (excellent or good, 71%) compared with those with associated lesions in the same limb (excellent or good, 44%). A reduction of movement was frequently observed, particularly in pronation and supination, which was limited in 28% of the cases and abolished in 15%. In 4 patients there was a significant increase in cubitus valgus. Arthrosis was present in 45% and periarticular calcification in 74% of the cases. There were 5 cases of radioulnar synostosis and 4 cases of myositis ossificans. Subluxation of the distal radioulnar joint was observed in 26 wrists, 4 of which were painful. The results of resection of isolated fractures may be considered acceptable, while the prognosis of fractures with associated lesions is more unfavourable. PMID- 2599850 TI - The ilizarov apparatus in the treatment of thalamic fractures of the calcaneus. AB - The authors present a new method for the treatment of severe thalamic fractures of the calcaneus by the Ilizarov apparatus. The versatility of this apparatus makes it possible to restore the anatomy of the area, in particular, the total height of the talo-calcaneal complex and correction of varus or valgus deviation while leaving the ankle joint free. This method was used to treat 10 cases of severe thalamic fracture. If the apparatus is maintained for at least 3 months there is no subsequent loss of correction and the results are very good. PMID- 2599851 TI - External fixation of fractures and fracture dislocations of the pelvis. AB - External fixation of pelvic fracture dislocations is appropriate when reduction must be accomplished by noninvasive methods which are nonetheless capable of precise regulation. The corrective frames described can be applied with minimal trauma and are capable of orientating the necessary corrective forces in the required directions to reduce the wide variety of bony displacements and dislocations encountered in these injuries. The apparatus is flexible and the choice of particular technique and assemblies is determined by evaluating the biomechanics of the mechanism of injury and applying the appropriate antagonist forces. These forces operate in three fundamental planes: anteroposterior, lateral and vertical. The author describes and illustrates how the assembly may be used to operate in these planes and reduce and stabilise a variety of displacements encountered in fractures and fracture dislocations of the pelvis. PMID- 2599852 TI - Osteosynthesis of fractures of the femoral neck by nail-plate, screws and valgus osteotomy. AB - The authors describe the method used for the treatment of subcapital fractures of the femoral neck in younger subjects. This method associates intertrochanteric osteotomy with osteosynthesis using one or two spongy bone screws and a nail plate. The series includes 26 patients followed up both clinically and radiographically. The results were very good, with 100% union and only 4 cases of ischaemic necrosis (15%). PMID- 2599853 TI - The treatment of congenital clinodactyly of the hand. AB - Based on a review of 49 cases (involving 92 digits) of clinodactyly of the hand the authors analyse the cause, associated deformities and amount of time and procedures required for treatment. What emerges in particular is the importance of the age at which corrective surgery is performed. PMID- 2599854 TI - Freeze-dried bank bone. AB - The authors present their experience with freeze-dried bone of human origin. Since 1983, 500 preserved allografts have been implanted in 228 patients. The implants were monitored radiographically and, based on perfect fusion with the recipient bone, the results were as follows: excellent: 78%; good: 8.6%; failure: 12.4%. In nearly all the cases of failure this was attributed to an erronous implant method or an improper use of the graft. Bank bone is only osteoconductive: thus, in the absence of osteogenetic properties, a perfect method of implant and its correct use are essential. PMID- 2599855 TI - The treatment of fractures of the surgical neck of the humerus by osteosynthesis with Kirschner wires. AB - Seventy-one patients treated for fracture of the surgical neck of the humerus by osteosynthesis with Kirschner wires inserted percutaneously were followed up. The method is described in detail, and its indications and limitations are discussed. The clinical and radiographic results were extremely positive, with minimal complications and a much reduced work load on the part of the surgical team. PMID- 2599856 TI - A rare case of intraspinal ganglionic cyst. AB - The authors describe a case of intraspinal extradural ganglionic cyst. This is a rare condition which has not previously been reported in the literature. The differential diagnosis is discussed. PMID- 2599857 TI - An unusual finding in nerve root compression at L5 caused by herniated disc. AB - The authors describe the severe changes observed in the L5 nerve root in a patient aged 46 years with lumbar disc herniation at L4-L5. The lesions observed in the nerve root made it unrecognisable, thus we could not be certain that we were actually dealing with a nerve root until it was confirmed by histological examination. The severe macroscopic and microscopic changes observed had resulted in complete loss of function in the nerve root, so its removal did not cause any changes in the neurological, clinical or electromyographic pictures. PMID- 2599858 TI - Intervertebral disc herniation at D3-4 Case report. AB - The authors report a case of intervertebral disc herniation at D3.4 which they removed surgically from a posterior approach. They emphasize the extreme rarity of this localisation. The hernia was calcified, extruded and displaced posterolaterally and medially, causing pressure on the anterior aspect of the spinal cord with neurological signs of the pareto-spastic type. The operation was successful, with relief of pain and regression of the neurological symptoms. PMID- 2599860 TI - Congenital dislocation of the hip. A protocol for early diagnosis. AB - On March 13, 1987 the Academy of Sciences and the Medico-Surgical Association of Ferrara organised a Meeting in Ferrara to commemorate Professor Marino Ortolani on the occasion of the 50th anniversary of his publication of the click sign which he proposed as an early means of diagnosis in congenital dislocation of the hip. It was thought that the 50th anniversary of the description of this sign would be a fitting occasion on which to compile a joint orthopaedic, radiological and paediatric document in which current views on the early diagnosis of congenital dislocation of the hip could be reported. The proposal was taken up and sponsored by the following Italian Associations: Orthopaedic Surgery, Paediatric Orthopaedics, Radiology and Nuclear Medicine, Paediatrics, Preventive and Social Paediatrics. A committee was formed representing the various Associations, to which was entrusted the task of compiling the proposed document. PMID- 2599859 TI - A case of anterior interosseous nerve syndrome. AB - Anterior interosseous nerve syndrome is a rare anomaly. The author describes a case which is of particular interest because of its iatrogenic pathogenesis and the clinical picture of isolated defect of flexor pollicis longus. The importance of electromyography is emphasized. Recovery occurred approximately 5 months after the onset of the neuropathy as a result of conservative treatment and without recourse to surgery. PMID- 2599861 TI - Centralized diagnosis and therapy of tumors of the bone and soft tissues. PMID- 2599862 TI - Strategic planning for nursing homes: a market opportunity analysis perspective. AB - Market opportunity analysis is a framework for systematic strategic planning involving the analysis of demand, market segments, competition, industry, and channels of referrals. This approach enables nursing homes to select target markets and to design marketing programs to attract those target markets. PMID- 2599863 TI - Union election activity in the hospital industry. AB - In the past five years, there has been a dramatic decrease in the number of representation elections in the hospital industry. Once a union is in place, however, decertification is less likely to occur than in other industries. PMID- 2599864 TI - The influence of entrepreneurs in medical rehabilitation. AB - Entrepreneurial influence in medical rehabilitation has been significant. However, the current relationship between acute care and medical rehabilitation is growing tenuous. PMID- 2599866 TI - Use marketing to reduce malpractice costs in health care. AB - Marketing may have contributed to malpractice litigation by elevating public expectations. If all of the four basic functions of marketing--intelligence, strategy, operations, and communications--are applied well, then marketing may have a significant impact on malpractice risks and costs. PMID- 2599865 TI - Health care. PMID- 2599867 TI - Decreasing medical malpractice: toward an organizational systems approach. AB - Using a systems model, the authors offer malpractice reduction strategies and actions in five subsystems of the organization: technical, structural, psychosocial, managerial, and cultural (goals and values). PMID- 2599868 TI - Reorganization/diversification: six years later. AB - Hospital efforts in diversification strategies have met with mixed reviews. After a slow beginning and some difficult learning experiences, this hospital organization found a successful approach. PMID- 2599869 TI - Hospital-church relationships. PMID- 2599870 TI - HCMR interview: what's ahead for rural health care. Interview by Barbara P. McCool. PMID- 2599871 TI - An application of the pure-play technique. PMID- 2599872 TI - HVA wins fair grades for sickle cell specialists. Health Visitors' Association. PMID- 2599873 TI - Keeping babies warm: have we got it right? AB - Concern has recently centred on the risks of babies overheating in their cots at night. We review the conditions under which babies sleep at home, and their effects on body temperature. Parents do not choose room heating, clothing and wrapping at random, but according to a 'formula' based on perceived risk to the infant of cooling. This formula allows 95 per cent of 3-4 month babies to produce controlled fall in body temperature at night, but most have to cooly by active thermoregulation, which relies heavily on the head as a route of heat loss. We conclude with some general recommendations about room heating and wrapping of babies which may reduce the risk of thermal stress during sleep. PMID- 2599874 TI - Having a baby on a neonatal unit: what do parents feel? How can health visitors help? AB - Having a baby on a neo-natal unit can be traumatic for the parents. This article looks at the role of health visitors in providing care to such families. PMID- 2599875 TI - Prescriptions for health visiting. AB - Building on studies of the experience of health visiting, this article makes recommendations about staffing levels, clerical assistance, role definition, counselling, supervision groups, home/work management, job appraisal, career development, training, quality circles, liaison, communication, senior nurse roles and organizational structure and ethos. It calls for more participative management styles and greater involvement of health visitors in human resource management and administrative decision-making. Previous research on the health visitor's role 1, 2, 3, 4, 5, 6 have provided insights into the experience of health visiting. Drawing on these insights and the theory and practice of occupational psychology, a number of recommendations are offered for improving well-being and effectiveness among health visitors. These recommendations are aimed at promoting discussion of issues which emerged as contentious in the research. They are based on studies conducted in three separate and distinct areas of the country which may not be entirely representative. Furthermore, the suggested practices may already be implemented in other areas. PMID- 2599876 TI - Paediatric surveillance--a calendar for change. AB - A course was held for health visitors to evaluate their present practice in paediatric surveillance. Problem areas were highlighted and a set of recommendations produced which sought to improve practice and bring about a calendar for change. PMID- 2599877 TI - China's one child policy . . . some considerations. AB - Between 1949-1968 China--which has more than one-fifth of the world's people- experienced an upward trend in population growth rate. China's one-child family policy was introduced in the late 1970s. It aims to limit population to around 1200 million by the year 2000. In order to achieve this goal, birth rates will need to decrease dramatically. PMID- 2599878 TI - Hb Fontainebleau [alpha 21(B2)Ala----pro], a new silent mutant hemoglobin. AB - Hb Fontainebleau [alpha 21(B2)Ala----Pro] was found in a family of Italian origin. This new variant has electrophoretic properties identical to those of Hb A with the exception of isoelectrofocusing in which it migrates like Hb A1c. The introduction of a prolyl residue at the beginning of the B helix in the alpha chain does not lead to a change in the stability or oxygen binding properties of the hemoglobin molecule. PMID- 2599879 TI - Hb Luxembourg [alpha 24(B5) Tyr----His]: a new unstable variant. AB - Hb Luxembourg [alpha 24(B5)Tyr----His] was found in association with mild hemolytic anemia and increased indirect bilirubinemia in a family originating from the Netherlands. The slight instability of this variant may be the consequence of an indirect effect of the substitution on the alpha 1 beta 1 contact since position alpha 24 (B5) is internal and in contact with several residues involved in this interface. PMID- 2599880 TI - Hemoglobin Windsor or beta 11 (A8)Val----Asp: a new unstable beta-chain hemoglobin variant producing a hemolytic anemia. AB - A new beta-chain variant, Hemoglobin Windsor [beta 11 (A8)Val----Asp] was discovered in a 9-month-old child who presented with a hemolytic anemia of 59 g/l with an intercurrent viral infection. Her blood film demonstrated fragmented cells, target cells, stipple cells, nucleated red cells, polychromasia and some spherocytes, indicative of acute hemolysis. Hemoglobin electrophoretic studies were requested and a beta-chain variant, constituting 27% of the total hemoglobin, separated towards the anode under alkaline conditions. The variant was unstable, producing numerous "Hb H"-like inclusions and a positive isopropanol stability test. The variant hemoglobin was purified by precipitation. The variant beta-chain was purified by column chromatography and its tryptic peptides fractionated by high performance liquid chromatography. Amino acid analysis and sequence data indicated that the valine at position 11(A8) had been substituted by an aspartic acid residue. This substitution, in the bottom of the heme pocket, has resulted in instability of the hemoglobin molecule and an increase in oxygen affinity. The variant appears to have resulted from a spontaneous mutation as both parents are hematologically normal. A younger sibling is also hematologically normal. PMID- 2599881 TI - Hb Bruxelles: alpha 2A beta (2)41 or 42(C7 or CD1)Phe deleted. AB - Hb Bruxelles is a new beta-globin variant producing severe congenital Heinz body anemia. It results from the deletion of one of the two adjacent phenylalanines, beta 41 or beta 42, presumably by frameshift mutagenesis. Its whole blood oxygen affinity is significantly lowered. PMID- 2599882 TI - Rapid HPLC techniques for globin chain synthesis studies. AB - Globin chain synthesis and alpha/beta ratios were determined in a number of normal subjects, alpha-thalassemia-2 homozygotes, and beta-thalassemia trait using three different techniques. Cation exchange high performance liquid chromatography on a Pharmacia Mono-S, HR 5/5 and reversed phase high performance liquid chromatography on a semi-preparative Vydac C4 column were compared with the traditional carboxymethylcellulose chromatography. Both high performance liquid chromatography columns give excellent results when 2 mg of hemoglobin was chromatographed in each analysis. By modifying the protocols for column equilibration and gradient shape for preparative Vydac C4 columns, conditions were found yielding excellent resolutions of the labeled globin chains in less than an hour without the need for substantial increase of the flowrate. This method was found to be superior to other methods and may be a suitable alternative for the classical carboxymethylcellulose chromatography. Up to five specimens could easily be analyzed in a single day with this system. PMID- 2599883 TI - Hb Volga [B27 (B9) AlA----AsP], a possible de novo mutation in a Danish person. PMID- 2599884 TI - Hb Olympia [beta 20 (B2) Val----MeT] in a Swedish family. PMID- 2599885 TI - Hb G-San Jose homozygosis in a Calabrian family. PMID- 2599886 TI - Hb Extremadura or alpha 2 beta 2133 (H11)Val----Leu, a new mildly unstable hemoglobin in a Spanish female. PMID- 2599888 TI - First report of HB Long Island-Marseille in Australia--a chance discovery. PMID- 2599889 TI - The death of a child: Part III. PMID- 2599887 TI - Hb Brockton [alpha 2 beta 2138(H16)Ala----Pro] observed in a Turkish girl. PMID- 2599890 TI - The child and family facing death. AB - When children are diagnosed with life threatening illnesses such as cancer, their lives and their families' lives are changed forever. The nurse has valuable roles as advocate, facilitator, teacher, and support throughout the child's illness and death. The purpose of this article is to provide practical and applicable information to nurses regarding their clinical practice with children and families facing death. PMID- 2599891 TI - The use of art therapy and group process with grieving children. PMID- 2599892 TI - Disappointment and its application to the grief process for parents whose child has a severe anomaly or dies. PMID- 2599893 TI - After a child dies: a funeral director's perspective. AB - This article will describe the grieving process and look at the role of the funeral director. It explains what the family should expect during the funeral experience, outlining options available to the family concerning services, disposition of the remains, and legal requirements. It also examines the embalming and restoration of remains. Finally, the stress of the funeral process on the funeral director will be discussed. PMID- 2599894 TI - Grieving alone: a single mother's loss. PMID- 2599895 TI - Shattered dreams. PMID- 2599896 TI - The Tiger in my life. PMID- 2599897 TI - When a family loses a child. PMID- 2599898 TI - A reporter experiences death. PMID- 2599899 TI - The unforgettable Len Dawson. PMID- 2599900 TI - Sudden death and the police officer. PMID- 2599901 TI - Dealing with pediatric death and dying: a prehospital caregiver's perspective. PMID- 2599902 TI - Epidermoid carcinoma of the anal canal treatment results and prognostic variables in a series of 242 cases. AB - From 1972 to 1985, 260 cases of anal canal epidermoid carcinoma were irradiated. Eighteen cases treated for palliation were excluded from the study; 242 (93%) were treated with curative intent. The sex ratio was 1/5.5; mean age was 66 years. HISTOLOGY: 60.3% were well differentiated epidermoid carcinoma; 31.0% moderately differentiated and 8.7%, cloacogenic cases. Staging: T1: 11.5%; T2: 16.1%; T3a: 17%; T3b: 33.5%; and T4: 21.9%. Abnormal inguinal nodes were present in 15.3% of cases. Crude overall survival (Kaplan-Meier) for the 242 cases is 86.4% at 1 year, 63.9% at 3 years, 51.2% at 5 years, and 30.8% at 10 years. Radiation therapy was the sole treatment for 193 cases. No chemotherapy was given. Patients were irradiated by external beam. They received a first course of X rays (mostly 18 MV, some 6 MV) 40 to 45 Gy (box technique) over 4 to 5 weeks in the pelvis. Age and size of tumor were considered when deciding on the target volume. After a rest period of 4 to 6 weeks, a second course of 15 to 20 Gy in 2 weeks was given through a perineal field by electron-beam of suitable energy. The mean total dose was 60.56 Gy and median was 62.5 Gy; the mean overall treatment duration was 85.3 days (median 82 days) and the mean Time Dose Factor including decay factor was 98.96. In this group, 5-year determinate survival was: T1-T2, 84.5%; T3a, 74.8%; T3b, 64.9%; T4, 58.9%. In 147/193 patients (76.2%) local control was achieved. The overall anal conservation rate was 62.6%. In 106 cases (55%), the anus had maintained normal function. The 5-year survival rate by N was 73.3% in the absence of inguinal nodes (169 cases) and 36.1% if such nodes were present. There was no significant difference in survival rate according to histological type. In the second group, receiving radiation therapy plus surgery, 33/49 cases (T3b-T4) were irradiated before surgery (median dose 40.5 Gy). Post operative radiation therapy was administered in 16 cases (T3b-T4) (median dose 49.6 Gy). The 5-year determinate survival is 53.2% for T3b and 79% for T4. According to the log-rank test, there was no significant difference between survival with radiation therapy alone and radiation therapy plus surgery. Multivariate analysis of the whole group indicated that T stage is the only predictive variable.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2599903 TI - Radiotherapy for anal cancer: experience from 1979-1987. AB - Seventy patients with squamous cell carcinoma or cloacogenic carcinoma of the anus treated from 1979-1987 were reviewed. Five groups were analyzed: (a) local excision (LE) with postoperative radiotherapy (n = 9); (b) abdominoperineal resection (APR) with either pre- or postoperative radiotherapy (n = 22); (c) definitive radiotherapy alone (n = 8); (d) radiotherapy with continuous 5 Fluorouracil (5-FU) infusion (chemoradiation) (n = 25); and (e) patients treated for recurrent disease (n = 6). Abdomino-perineal resection and radiotherapy resulted in an actuarial local control (LC) rate of 90% and an overall 5-year survival rate of 77% (median follow-up, 48 months). All patients in Group 1 and 5/8 patients in Group 3 had locally controlled disease and were disease-free. The chemoradiation protocol resulted in a complete clinical response rate of 75% (18/24, one patient died during treatment) assessed 4-6 weeks after treatment. The colostomy-free local control rate with chemoradiation is 67% (16/24). Local control was 50% for all stages receiving 45-49 Gy and 90% for those patients receiving greater than or equal to 55 Gy but was not correlated with total 5-FU dose. Abdomino-perineal resection was performed to salvage six patients with persistent disease and two with recurrent disease, resulting in an overall local control rate of 92% (22/24). The actuarial survival was 96% (median follow-up, 14 months; range, 1-30). The acute complications of radiotherapy included diarrhea and perineal skin reactions that were increased by 5-FU infusion. However, diarrhea can be ameliorated by a modified treatment technique that reduces irradiation to the small intestine. For the entire patient group, minor late complications occurred in 23%, and major complications occurred in 9%. PMID- 2599904 TI - Interstitial curietherapy in the conservative treatment of anal and rectal cancers. AB - Conservative treatment has become a valid alternative to radical surgery in most cases of cancer of the anal canal and in selected cases of cancer of the low rectum. In this strategy interstitial curietherapy has an appreciable role to play. The results of a series of 369 patients followed more than 3 years indicate that implantation of Iridium-192 is effective not as sole treatment but as a booster dose 2 months after a course of external beam or intracavitary irradiation. The dose delivered did not exceed 20 to 30 Gy and the implantations were always performed in one plane using either a plastic template or a steel fork. Three groups of cases must be considered: (a) among 221 patients with epidermoid carcinoma of the anal canal, the rate of death related to treatment failures was 20% and among the patients cured more than 90% retained normal sphincter function. (b) In 90 patients with T1-T2 invasive adenocarcinoma of the rectum, Iridium-192 was carried out after four applications of contact X ray therapy. The rate of control was 84%. (c) In 62 elderly, poor risk patients with T2-T3 tumor of the low rectum initially suitable for an abdomino-perineal resection, a tentative extension of the field of conservation was made using a split-course protocol combining a short course of external beam irradiation at a dose of 30-35 Gy in 10 fractions over 12 days and an Iridium-192 implant. The rate of death due to treatment failures was 14.5% and among the patients controlled 97% had a normal anal function. These results show that implantations of Iridium-192 may contribute to the control of anal and rectal cancers and may spare many patients a permanent colostomy, but the treatment requires great care in patient selection, treatment protocol, technical details, and follow-up. This treatment policy must be conceived as a team work of radiation oncologists and surgeons. PMID- 2599905 TI - Postoperative radiation therapy for incompletely resected colorectal carcinoma. AB - The efficacy of high-dose post-operative radiation therapy was evaluated in 56 patients with pathologically proven or suspected residual disease after surgical resection of colon or rectal carcinoma. Patients had either microscopic or gross residual. They were treated with pelvic or abdominal irradiation to a dose of 4500 cGy followed by boost therapy to as much as 6000 to 7000 cGy if small bowel could be moved from the radiation field. Patients with microscopic residual had a local failure rate of 30% compared to 57% in those with gross residual disease. Five-year disease-free survival was 45% in patients with microscopic versus 10.6% for those with gross residual tumor. There was a trend toward a dose response curve for those with microscopic disease, but none was noted with gross residual. In view of the limited results obtained with current external beam techniques, it is recommended that newer avenues, such as high-dose preoperative therapy combined with intraoperative radiation, be investigated in this poor prognosis group. PMID- 2599907 TI - Carcinoma of the uterine cervix stage IB and early stage II. Prognostic value of the histological tumor regression after initial brachytherapy. AB - In our center limited centro pelvic invasive carcinomas of the uterine cervix (less than 4 cm) are treated with brachytherapy and surgery. With these therapeutic modalities no residual carcinoma was observed for 80% of the patients. The purpose of this study was to evaluate our results with this treatment, and to evaluate the prognostic value of the pathological status of the cervix. From 1976 to 1987 we have treated 115 patients with these modalities. Staging system used was the FIGO classification modified for Stage II (divided in early Stage II and late Stage II). Patients were Stage IB (70 cases) and early Stage II (45 cases); 60 Gy were delivered with utero vaginal brachytherapy before any treatment. Six weeks later a radical hysterectomy with pelvic lymphadenectomy was performed. Twenty-one patients with positive nodes received a pelvic radiotherapy (45 to 55 Gy). Local control rate was 97% (100% for Stage IB and 93% for early Stage II). Uncorrected 10-year actuarial survival rate was 96% for Stage IB and 80% for early Stage II patients. No treatment failure was observed for Stage IB patients. Ninety-two patients (80%) had no residual carcinoma in the cervix (group 1) and 23 patients (20%) had a residual tumor (group 2). The sterilization rate of the cervix was 87% for Stage IB tumors versus 69% for early Stage II, and was 82% for N- patients versus 68% for N+ patients. Ten year actuarial survival rate was 92% for group 1 and 78% for group 2 (p = 0, 1). Grade 3 complications rate was 6%. We conclude that brachytherapy + surgery is a safe treatment for limited centro pelvic carcinomas of the uterine cervix (especially Stage IB) and that pathological status of the cervix after brachytherapy is not a prognostic factor. PMID- 2599906 TI - External irradiation plus curietherapy boost in 108 base of tongue carcinomas. AB - From 1960 to 1983, 108 patients underwent an association cobaltherapy plus curietherapy boost for a base of tongue carcinoma. This group included 18 T1 tumors, 39 T2, and 51 T3. Cobaltherapy was delivered to a dose of 45 Gy/4.5 weeks to the primary site and the neck. It was completed by an electron boost or a nodal surgery in case of initial nodal disease. Two techniques of Curietherapy were used: plastic tubes and guide-gutters. As most of these implants have been done before 1975, all the doses have been recalculated on the 85% isodose according to the Paris system. They varied from 22 to 88 Gy. The tolerance of the implantation was excellent. Five-year survival of the whole group is 26%. The local control rate is 85% for T1 tumors, 50% for T2, and 69% for T3. Despite the importance of cumulated doses, a few necrosis were observed. Considering the poor outlook of this cancer, its treatment by exclusive radiotherapy requires very high doses which can only be delivered without major sequellae or complication by a combination of cobaltherapy and curietherapy boost. PMID- 2599908 TI - Response of aorta and branch arteries to experimental intraoperative irradiation. AB - Injury to the aorta was evaluated in dogs 2 and 5 years after fractionated irradiation (EBRT), intraoperative irradiation (IORT) or a combination. Doses greater than 20 Gy IORT combined with 50 Gy EBRT given in 2 Gy fractions or 30 Gy IORT alone were accompanied by a significant risk of aneurysms or large thrombi as determined at necropsy 4 to 5 years following irradiation. Narrowing of the aorta as detected by aortography occurred at 5 years but was not detected earlier. The ED50 for aortic narrowing was 38.8 Gy IORT and 31 Gy IORT plus 50 Gy EBRT. The ED50 for branch artery injury was 24.8 Gy IORT alone and 19.4 Gy IORT plus 50 Gy EBRT. The difference in ED50s for IORT alone and IORT plus EBRT indicates that the contribution of the EBRT dose in terms of an IORT dose for aortic narrowing was 7.8 Gy and for branch artery injury was 5.4 Gy. The ED50 for incidence of small thrombi in the aorta was about 29 Gy for IORT alone and 23.5 Gy for IORT combined with EBRT. Fibrous thickening of the adventitia was measured and the effect of the 50 Gy EBRT component of a combination of EBRT and IORT was determined to be equivalent to 10 to 12 Gy IORT. Based on the various estimates, IORT doses of 10-15 Gy have an effect of 5 times or greater the amount given in 2 Gy fractions. At all EBRT doses and at lower IORT doses the intima was greatly thickened. At IORT doses of 20 Gy or above there was a dose related decrease in intimal thickness to near normal values. This was probably due to cell killing or inhibition of intimal proliferation that predominated at higher doses. Although the risk of serious vascular complications appears low following IORT of humans, this may be due to short observation times and the fact that IORT doses currently used are usually 20 Gy or less; this may be near the tolerance for late response of larger arteries. Only one dog in this study had complete rupture of the aorta causing death. Five other dogs at high IORT doses had near ruptures of the aorta but were clinically normal. PMID- 2599909 TI - Radiobiological comparison of external beam irradiation and radioimmunotherapy in renal cell carcinoma xenografts. AB - Growth delay was measured in TK-82 renal cell carcinoma (RCC) xenografts implanted in nude mice receiving single fraction external beam irradiation (SF XRT), multifraction external beam irradiation (MF-XRT), or radioimmunotherapy (RIT). Thermoluminescent dosimeter(s) (TLD) and autoradiography were used to ascertain the average absorbed dose delivered and the degree of heterogeneous uptake of radiolabeled antibody for the RIT irradiations. For intravenous administered activities of 100, 200, 400, and 600 microCi of I-131 labeled A6H antibody, volume doubling times (VDT) and TLD absorbed dose measurements for each administered activity were 7 days (341 cGy), 38 days (383 cGy), 85 days (886 cGy) and no regrowth (1034 cGy), respectively. For SF-XRT irradiations of 500, 1000, and 1500 cGy, VDT times were 11, 62, and 103 days, respectively. MF-XRT of 4 X 250 cGy over a 2-week period yielded a VDT of 25 days. Marked peripheral activity deposition was noted on most autoradiographs from multiple tumor samples. These data suggest that an equivalent to superior tumor growth delay is obtained for absorbed doses delivered by exponentially decaying low dose rate radioimmunotherapy RIT compared to similar doses of acute dose rate XRT as quantitated by the TLD method. PMID- 2599911 TI - The patients perception of her breast following radiation and limited surgery. AB - Seventy-four patients followed from 1 to 8 years post completion of breast conserving surgery and radiation for early-stage breast cancer were asked to answer a questionnaire exploring their perception and awareness of the treated breast. The questionnaire was divided into several sections, including "Daily Activities", Pre-menstrual Changes", "Sexual Activities", and a summary "Satisfaction Index" section; when appropriate, comparisons were sought between the treated and untreated breasts. Preliminary results from this study indicate that 70% of all patients are aware of their treated breast in some way during everyday activities. The "Satisfaction Index" of this patient group is very high, with 75% rating their cosmetic result, and 81% their functional result "8" or higher on a scale of "0" to "10","10" indicating "best" or "normal". PMID- 2599910 TI - Histopathological changes of human tumors following thermoradiotherapy. AB - Twenty human malignant tumors treated with thermoradiotherapy were examined histopathologically. Hyperthermia was administered regionally with a 13.56-MHz or 8-MHz RF heating device, once or twice a week after irradiation, 2 to 12 sessions in total. Fifteen tumors received a total radiation dose of 26 to 70 Gy in fractions of 1.8 Gy to 2.0 Gy a day, 5 days a week, whereas five tumors received a total dose of 20 to 60 Gy in fractions of 4 Gy each, twice a week. Microscopic examination of 4 of the 20 tumors revealed complete necrosis throughout the cross section of the entire tumor. All the four tumors had received a total dose of over 60 Gy and a tumor center temperature of over 42 degrees C. In 10 tumors, more than 50% but less than 99% of the cross-section of the entire tumor had massive coagulation necrosis. The remaining six tumors showed relatively little change; the area of intratumor necrosis was less than 50%. The grade of tumor necrosis was dependent on both the temperatures of tumor center and periphery, and a total radiation dose. The small blood vessels and capillaries in the tumor parenchyma were markedly damaged in 16 of the 20 tumors, while the blood vessels in the tumor stroma were damaged in only 2 tumors. Condensation of the destroyed nucleus observed in 15 tumors was considered to be a typical change induced by thermoradiotherapy. Viable tumor cells remained in the tumor central area in only four tumors and around the blood vessels in only three tumors. However, in the tumor peripheral area, viable tumor cells were observed in 16 out of the 20 tumors. These results indicate that histopathological changes induced by thermoradiotherapy are greater in the tumor central area than in the tumor peripheral area, and provide strong rationale for utilizing full dose radiation therapy in combination with hyperthermia as opposed to lower doses for cancer therapy. PMID- 2599912 TI - Brachytherapy as part of the definitive management of squamous cancer of the base of tongue. AB - Between 1981 and 1986, 17 patients were treated at the Department of Radiation Oncology at the Memorial Sloan-Kettering Cancer Center with squamous cancer of the base of the tongue whose definitive treatment included brachytherapy. The patient sample consisted of 14 men and 3 women with age range of 35 to 71 years (median = 58). There were four patients with T1 lesions, six with T2, six with T3, and one with T4. In general, treatment consisted of 5000-5400 cGy with external beam radiation and 2000-3000 cGy boost to the base of tongue via an Ir 192 implant using afterloading catheters. Necks were managed with elective radiation alone in the N0 group (n = 5) or with radiation plus neck dissection in the N+ group (n = 12). Five patients who would have required laryngectomy had they undergone primary surgery received neoadjuvant chemotherapy followed by external beam and implant as part of a larynx preservation study that was being done at our institution (4-T3, 1-T2). The range of follow-up is 8 to 59 months, with median follow-up of 24 months. No patients have been lost to follow-up. Crude local control by T-Stage are as follows: T1-4/4, T2-5/6, T3-5/6, T4-1/1. Actuarial local control at 24 months is 87%. There have been no neck failures. There have been five patients who had soft tissue ulceration (STU) and one patient who had osteoradionecrosis (ORN). All soft tissue ulceration patients have been successfully managed conservatively. The patient with osteoradionecrosis is currently being managed. In 4 of these 6 cases, the implant was the initial therapeutic intervention and the entire tumor bed was implanted. On the other hand, when external beam was the initial treatment, the boost was administered to the smaller volume of residual disease. Overall, 4 of 7 patients who had implant first developed either soft tissue ulceration or osteoradionecrosis, as opposed to 2 of 10 patients who had implant after external beam and/or chemotherapy. The numbers are too small to be statistically significant, but our current policy is to perform brachytherapy after the external beam. In addition, all those with either soft tissue ulceration or osteoradionecrosis were implanted with a non-looping technique. Overall, 6 of 12 patients treated with a non-looping technique developed an injury, whereas none of the five treated with a looping technique has developed one.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2599913 TI - Considerations on recombination losses in ionization chambers using pulsed electron beams with beam scanning. AB - Based on Boag's theory, referring to saturation effects in ionization chambers with pulsed electron beams, we developed a simple method of determining recombination losses. The correction factors for chamber readings result from slope and intercept of a regression line M1/3 = f(M/V) obtained with at least two different chamber voltages, V, and chamber readings, M. The deviation of these correction factors, compared with those of Boag's precise theory, does not exceed +/- 0.5%. PMID- 2599914 TI - Ferromagnetic thermoseeds: suitable for an afterloading interstitial implant. AB - Previous studies have shown implantable ferromagnetic thermoseeds to be a promising hyperthermia method. However, migration from the implant site and chemical toxicity caused by corrosion of the thermoseed alloy have proven to be potential hazards. These problems could be overcome by placing the thermoseeds into removable catheters similar to those used for afterloading interstitial brachytherapy. As an additional merit, the method would allow convenient combination of heat and radiation therapy. To test the clinical performance of this method, we compared temperature distributions and biologic effects in canine muscle and transmissible venereal tumors for bare thermoseeds and thermoseeds contained within catheters. We found no significant difference in the heating patterns and similar tissue changes when all implants were removed immediately after heating. More severe tissue changes were present around bare thermoseeds that were retained. This suggests that catheters provide a safe and reliable method for thermoseed hyperthermia which would allow convenient combination with interstitial radiation. PMID- 2599916 TI - [ABC units (alternative birth care) in Sodersjukhuset]. PMID- 2599915 TI - Chemoradiation in brain tumors: assets vs. adverse effects. PMID- 2599917 TI - [Irregular working hours, exposure to laughing gas and pregnancy complications among midwives]. PMID- 2599918 TI - [The National Social Welfare Board's general advice about testing of newborn infants for certain metabolic disorders, etc]. PMID- 2599919 TI - Case report. Angle class II malocclusion. PMID- 2599920 TI - Design of bionators and bio-finishers using cephalometric analysis and bio finishers. Part 1. PMID- 2599922 TI - Testicular feminization in a cat. PMID- 2599921 TI - "Speciesism is the natural order". PMID- 2599923 TI - Radiographic bone surveys. PMID- 2599924 TI - Cautions against substitution of production medicine for "sick cow treatment". PMID- 2599925 TI - Investigating cross-reactions between Leptospira and Borrelia. PMID- 2599926 TI - Can veterinarians afford higher salaries for veterinary technicians? PMID- 2599928 TI - Veterinarians aid in Alaskan tragedy--offer advice for future mishaps. PMID- 2599927 TI - Taurine and arterial thromboembolism. PMID- 2599929 TI - AVMA Trust insureds determine future professional liability premiums. PMID- 2599930 TI - Veterinarians receive fines in chloramphenicol case, but maintain they did not illegally use chloramphenicol. PMID- 2599931 TI - Adverse drug reaction reports benefit veterinary medicine. PMID- 2599932 TI - Veterinary technicians: an endangered species? PMID- 2599934 TI - Reports from the Symposium on Avian Chlamydiosis. 125th annual AVMA meeting. Portland, Oregon, 1988. PMID- 2599933 TI - Some pointers on fee collection. PMID- 2599935 TI - Avian companions and the human-animal bond. PMID- 2599936 TI - A practitioner's view of the problem of avian chlamydiosis. PMID- 2599937 TI - Chlamydia spp infection in turkey flocks in Minnesota. PMID- 2599938 TI - Potential of a voluntary caged pet bird improvement program. PMID- 2599939 TI - The USDA requirements for control of chlamydiosis in imported birds. PMID- 2599940 TI - Current situation and alternatives for diagnosis and control of chlamydiosis in the Federal Republic of Germany. PMID- 2599941 TI - Phase II evaluation of doxorubicin for treatment of various canine neoplasms. AB - One hundred eighty-five dogs with histologically confirmed, measurable malignant tumors were used in a prospective study to determine the response to 2 doses of the anthracycline antitumor antibiotic, doxorubicin. Eighty-three dogs had been refractory to one or more previous treatment modalities (surgery, n = 54; chemotherapy, n = 22; radiation, n = 10; hyperthermia, n = 1; biological response modifier, n = 1). The extent of neoplastic disease was determined immediately prior to and 3 weeks after 2 doses of doxorubicin were administered (30 mg/m2 of body surface area, iv) 21 days apart. Eighty-four percent (n = 157) of the dogs received 2 doses of doxorubicin and were evaluated. Of the 28 dogs ruled ineligible, 4 had serious side effects to the first dose of doxorubicin, and 24 others acquired complications resulting from their malignant tumors. A partial or complete remission was obtained in 41% (64/157) of all evaluable dogs: 26% (11/43) of the dogs with carcinoma, 67% (42/63) of the dogs with lymphoma, and 22% (11/51) of the dogs with sarcoma. Tumors in which there was at least a 50% volume reduction (partial or complete remission) included malignant lymphoma (42/63), fibrosarcoma (1/14), solid follicular thyroid carcinoma (3/13), mammary adenocarcinoma (2/8), hemangiosarcoma (2/8), osteosarcoma (1/6), circumanal carcinoma (3/5), synovial cell sarcoma (2/3), undifferentiated sarcoma (2/3), nasal adenocarcinoma (1/2), liposarcoma (1/2), infiltrating lipoma (1/1), malignant melanoma (1/1), sclerosing mesothelioma (1/1), and neurofibrosarcoma (1/2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2599942 TI - Acute and short-term toxicoses associated with the administration of doxorubicin to dogs with malignant tumors. AB - One hundred eighty-five dogs with histologically confirmed, measurable malignant tumors were used in a study to determine the toxicity of the anthracycline antitumor antibiotic, doxorubicin, which was administered once or twice (at a 21 day interval) at the rate of 30 mg/m2 of body surface area, iv. During this study, 7 dogs died as a direct result of doxorubicin-induced toxicosis and 16 died as a direct result of the malignant neoplastic disease. Each dog was evaluated for signs of toxicosis for 3 weeks after the last dose was administered (15 dogs received 1 dose, 170 dogs received 2 doses) or until the dog died, whichever came first. The most common signs of toxicosis were vomiting, diarrhea, colitis, anorexia, and pruritus. The probability of doxorubicin-induced toxicosis decreased significantly (P less than 0.0001) in inverse relationship to body weight. Dogs with signs of toxicosis during the 21-day interval from administration of the first dose of doxorubicin were 17.2 times (P less than 0.01; 95% confidence interval; 5.5, 54.2) more likely to develop signs of toxicosis during the 21-day interval from the second dose of doxorubicin. The performance status of each dog was evaluated using a modified Karnofsky performance scheme; the only time the performance status was adversely affected to a significant extent by doxorubicin-induced toxicosis was during the 21-day period, starting with the second dose (P less than 0.0001). PMID- 2599943 TI - Allergic inhalant dermatitis attributable to marijuana exposure in a dog. AB - Exposure to marijuana was believed to be responsible for clinical signs consistent with allergic inhalant dermatitis in a dog. The dog had facial and pedal pruritus associated with bilateral ocular discharge. Clinical signs resolved when the dog was kenneled, but returned when the dog was returned to its home. The results of intradermal skin testing, using a standard tray of 51 inhalant extracts, did not adequately account for the dog's clinical signs. Later, the owners indicated that previous residents of the owners' home had cultivated marijuana intensively inside and outside of the home. Intradermal skin testing with a source of marijuana pollen extract was performed, yielding a positive reaction in the dog and a negative reaction in another dog without clinical or historical evidence of allergic inhalant dermatitis. The affected dog was treated successfully and exclusively by hyposensitization with marijuana pollen extract. PMID- 2599944 TI - Unusual anatomic variation of bilateral ectopic ureters in a dog. AB - An unusual anatomic variation of bilateral ectopic ureters was diagnosed in a 6 week-old female Siberian Husky with urinary incontinence. Assessment during surgery revealed bilateral ectopic ureters with a common opening in the proximal portion of the urethra. Ureteroneocystostomy was performed bilaterally. After surgery, intermittent urinary incontinence continued, but was less severe. After resection of a persistent hymen in the 6-month-old dog, incontinence appeared to resolve, but then recurred, and has been controlled by phenylpropanolamine administration. PMID- 2599945 TI - Extramedullary plasmacytoma and immunoglobulin-associated amyloidosis in a cat. AB - Extramedullary plasmacytoma with immunoglobulin-associated amyloidosis was diagnosed in a 10-year-old cat. The primary tumor was a large, circumferential mass of the right tarsal region. Metastasis developed in the regional lymph nodes, spleen, and liver. Permanganate-resistant amyloid deposits were associated with plasma cells in the primary and metastatic tumors. Treatment with prednisone and melphalan had little effect on the progression of the disease, and the cat died four weeks later. PMID- 2599946 TI - Esophageal obstruction as a sequela to ruptured esophagus in a goat. AB - Granulation tissue as a sequela to ruptured esophagus was diagnosed as the cause of esophageal obstruction and regurgitation in a 3.5-year-old Toggenburg buck. Thoracic radiography was useful in localization of the problem. The condition was successfully treated by removal of the granulation tissue through left-sided thoracotomy. PMID- 2599947 TI - Urethral obstruction in a male llama. AB - An 8-year-old sexually intact male llama was euthanatized because of obstruction of the penile portion of the urethra and rupture of the urinary bladder. Clinical signs of obstruction included anorexia, lethargy, teeth grinding, straining to defecate, inability to urinate, and tense abdomen. Laboratory findings included anemia, leukocytosis with left shift, high serum urea nitrogen, creatinine, and phosphorus concentrations, and low serum chloride concentration. Necropsy revealed ruptured urinary bladder and acute fibrinous peritonitis. A firm, gray, nonmineralized urethral plug occluded the penile portion of the urethra for a distance of 14 cm in the midpenile region, distal to the sigmoid flexure of the penis. The urinary bladder mucosa and the urethra had microscopic evidence of chronic inflammation. Escherichia coli, Klebsiella sp, and alpha-streptococci were isolated from the urethral plug. PMID- 2599948 TI - Surgical excision of ectopic thyroid carcinoma involving the base of the tongue in dogs: three cases (1980-1987). AB - Localized thyroid carcinoma involving the base of the tongue was diagnosed in 3 dogs examined because of a midline cervical mass rostroventral to the larynx. These masses had been present for 4 to 12 months and were firm, nonsensitive, and fixed in position. One dog had progressive dysphagia and dyspnea. Masses were surgically excised together with the base of the tongue and portions of the hyoid apparatus. Severe dyspnea that developed immediately after surgery in 1 dog was managed by tracheostomy intubation for 4 days. Transient dysphagia developed in all dogs. Hydration was maintained by IV fluid administration until water and food of gruel consistency could be swallowed 1 to 6 days after surgery. Consistency of food was gradually thickened to normal, as swallowing improved 6 days to 2 months after surgery. One dog developed aspiration pneumonia that resolved after antimicrobial administration and improved swallowing that prevented further aspiration. After 9 months, 3 years, and 6 years, the dogs were clinically normal. PMID- 2599949 TI - Juvenile cellulitis in dogs: 15 cases (1979-1988). AB - The records of 15 dogs diagnosed as having juvenile cellulitis (juvenile pyoderma, puppy strangles) were evaluated for clinical, laboratory, and therapeutic results. Mandibular lymphadenopathy was observed in 14 dogs, and was not associated with skin lesions in 5 dogs. Edema, pustules, papules, or crusts were noticed periorally, periocularly, on the chin or muzzle, or in the ears of those dogs with skin lesions. Eight dogs were lethargic; fever and anorexia were inconsistent findings. Four dogs had signs of pain on manipulation of their joints. Complete blood counts revealed leukocytosis with neutrophilia in 4 dogs, and normocytic, normochromic anemia in 6 dogs. Three dogs had suppurative lymphadenitis with many neutrophils. Cytology of the aspirate of pustules or abscesses in 6 dogs revealed many neutrophils without bacteria. Coagulase positive Staphylococcus spp were isolated from draining lesions in 2 dogs. Intact abscesses and lymph nodes were negative for bacterial growth in 4 dogs. Three of these dogs were being administered antibiotics at the time of bacterial culturing. Cytology of the aspirates of joints in 3 of the 4 dogs with joint pain revealed suppurative arthritis with no bacteria, and the aspirates were negative for bacterial growth on culturing, although all 3 dogs were being administered antibiotics at the time of culturing. Of 12 dogs initially treated with antibiotics, only 4 (33%) responded favorably; the other 8 dogs were then given antibiotics and corticosteroids. Three dogs were initially given antibiotics and corticosteroids. All dogs treated concurrently with antibiotics and corticosteroids responded favorably. One of these dogs had a relapse after treatment was discontinued. The concurrent arthritis in 4 of the dogs resolved with treatment of the juvenile cellulitis and did not redevelop once the medication was discontinued. Concurrent treatment with antibiotics (cephalosporins) and prednisone (2.2 mg/kg of body weight/day) was the most consistently effective treatment in the dogs in this study. PMID- 2599950 TI - What is your diagnosis? Neoplasia of the right radius, probably osteosarcoma. PMID- 2599952 TI - Veterinarians train for Peace Corps assignments in Morocco. PMID- 2599951 TI - More on veterinary drug distribution channels. PMID- 2599953 TI - Residue screening tests: a solution in search of a need? PMID- 2599954 TI - The compulsive veterinarian--dedicated or obsessed? PMID- 2599955 TI - Let's proclaim a national animal week! PMID- 2599956 TI - Efficacy of ivermectin in the treatment of induced Parascaris equorum infection in pony foals. AB - Eighteen pony foals inoculated with 1,500 +/- 109 infective Parascaris equorum eggs were given 0.02 ml of ivermectin vehicle (liquid)/kg of body weight, PO, (control); 0.2 mg of ivermectin paste/kg, PO; or 0.2 mg ivermectin liquid/kg, PO, on postinoculation day (PID) 28. Foals were euthanatized on PID 42, and the small intestinal contents were examined for P equorum larvae. The mean number of fourth stage P equorum larvae in foals treated with ivermectin paste and liquid were 3.5 and 6, respectively. Significantly (P less than 0.01) higher mean numbers of larvae (1,250) were detected in foals treated with ivermectin vehicle. Larvae recovered from foals treated with ivermectin vehicle were of significantly (P less than 0.002) longer mean length than those from foals treated with ivermectin paste or liquid. Gross examination of lungs and liver revealed similar pathologic changes from the migration of P equorum in all foals. Adverse reaction to treatment was not observed. PMID- 2599957 TI - Economic and public health considerations of congenital toxoplasmosis in lambs. AB - Congenital toxoplasmosis was diagnosed in a flock of Hampshire sheep in South Dakota. The 80 ewes produced 144 lambs, 30 of which were born dead; toxoplasmosis was diagnosed in 11 of the dead lambs. The remaining 114 lambs grew normally, but 68 (40.3%) had agglutinating Toxoplasma gondii antibodies. Modified agglutination test T gondii antibody titers for 114 lambs were: less than 100 (n = 46), 64 (n = 2), 256 (n = 1), 1,024 (n = 12), and greater than or equal to 4,096 (n = 53). Tissues of 8 seropositive lambs were bioassayed for T gondii tissue cysts. Toxoplasma gondii was isolated from the tongue and lamb chops of 7, heart of 3, and legs of lamb of all 8 lambs. PMID- 2599958 TI - Evaluation of a colonic lavage solution to prepare the colon of the dog for colonoscopy. AB - Ten dogs were given 3 different doses (60, 80, and 100 ml/kg of body weight) of a commercial colonic lavage solution in 2 equally divided doses, 2 to 4 hours apart. The degree of colonic cleanliness was evaluated subjectively, using a numbered scoring system (1 = clean to 4 = excessive fecal material). Systemic and metabolic effects were assessed by comparing body weight, PCV, total protein concentration, serum osmolality, and urine specific gravity before and 24 hours after administration of the high-dose solution. The lowest mean cleanliness score (1.6) was obtained with the 80 ml/kg dose (P less than 0.001). The solution had no effect on any measurement except urine specific gravity (P = 0.036). Oral administration of a colonic lavage solution in a divided total dose of 80 ml/kg is a safe and effective method of large-intestine preparation in the dog. PMID- 2599959 TI - Comparison of an orally administered gastrointestinal lavage solution with traditional enema administration as preparation for colonoscopy in dogs. AB - Forty dogs were randomly assigned to be given either multiple enemas (group A) or orally administered lavage solution (group B) before colonoscopy. Dogs of group A (n = 20) were given 3 large-volume warm-water enemas 6 hours apart, with the last enema given 9 to 15 hours before colonoscopy. Dogs of group B (n = 20) were given a total dose of 50 ml of the lavage solution/kg of body weight through an orogastric tube. The lavage solution was administered in 2 doses of 25 ml/kg given 1 hour apart, 12 to 18 hours before colonoscopy. Dogs were monitored for changes in body weight and in serum sodium, potassium, chloride, calcium, phosphate, urea nitrogen, creatinine, and total CO2 concentrations. Colonoscopy was performed on dogs under general anesthesia by an investigator blinded as to the method of preparation, and the quality of preparation was subjectively evaluated. The quality of colon preparation was significantly (P less than 0.005) better after administration of oral lavage solution, compared with that after multiple enemas. There were minimal changes in laboratory values, side-effects were minimal, and biopsy specimen artifacts were not seen. Because proper patient preparation is necessary for complete colonoscopic examination, results suggested that an orally administered polyethylene glycol-containing electrolyte solution is preferable to administration of multiple enemas in preparing dogs for colonoscopy. PMID- 2599960 TI - Limb-sparing treatment for osteosarcoma in dogs. AB - Twenty dogs with spontaneously developing osteosarcoma of the extremities were treated with 1 of 3 multimodality limb-sparing procedures. Excision of the tumor was preceded by intra-arterial (IA) administration of cisplatin (cis diamminedichloroplatinum) alone directed to the affected extremity, irradiation plus IA administration of cisplatin, or irradiation plus IV administration of cisplatin. All dogs were free of apparent metastatic disease at the time of initial treatment. After diagnosis, dogs administered cisplatin IA had selective angiography performed on arteries supplying the tumor, and 70 mg of cisplatin/m2 of body surface was administered over 2 hours. This protocol was repeated 3 weeks later. Dogs that were irradiated received 25 or 40 Gy in 10 fractions over a 22 day period. The first and last radiation doses were immediately preceded by IA administration of cisplatin. Dogs given IV treatment received 10 mg of cisplatin/m2 2 hours before each radiation fraction was administered. Three weeks after the last treatment, tumors were excised and the limb underwent orthopedic reconstruction, generally using cortical allografting and bone plating. Limb function, allograft healing, local tumor control, and metastatic dissemination were monitored. Limb function was good to excellent in 69% (11/16) of dogs evaluated. Forelimb-sparing procedures were generally associated with better function than were limb-sparing procedures performed on hind limbs. Local tumor control was obtained in 79% (11/14) of dogs thoroughly evaluated, with local recurrences in 3 dogs at 3, 4, and 7 months after treatment. Fifteen dogs developed metastatic disease at a median time of 8 months from the time of diagnosis. Mean and median survival times for all dogs, regardless of cause of death, were 11.7 and 8 months, respectively. Tumor necrosis greater than 80% was statistically associated with lack of recurrence. Of 16 dogs, 5 (31%) developed infections at the surgical site. Multimodality limb-sparing treatment is believed to be a viable alternative for appropriately selected dogs with osteosarcoma. The optimal method of treatment prior to or after tumor excision has not yet been established. PMID- 2599961 TI - Bovine spongiform encephalopathy in a cow in the United Kingdom. AB - Bovine spongiform encephalopathy (BSE) was diagnosed in a cow with a history of behavioral change, apprehension, hyperesthesia to auditory and tactile stimuli, wide-based stance, and marked hind limb hypermetria. Myoclonus involving individual muscles was observed in the shoulder region, ventral cervical region, and upper portion of the hind limb. Clonus was observed in the forelimbs. Clinicopathologic findings were normal, except for high serum globulin concentration, which was attributable mainly to an increase in the gamma-globulin fraction. Results of electroencephalography revealed almost continuous high amplitude complexes in the occipital leads, interspersed with short runs of normal activity. There were generalized discharges, but these were not periodic. Current theory implicates the scrapie agent (prion) as the causal agent for BSE. The presence of scrapie in, and the possible entry of prion into bovine feedstuffs could result in the emergence of BSE in the United States. PMID- 2599962 TI - Idiopathic pleural effusion and pulmonary thromboembolism in a dog with autoimmune hemolytic anemia. AB - Pleural effusion and pulmonary thromboembolism were diagnosed in a dog with autoimmune hemolytic anemia. Clinical signs of tachypnea, then dyspnea in association with pleural effusion, developed after 10 days of immunosuppressive corticosteroid therapy (greater than 2 mg/kg of body weight/d, PO). The diagnosis of pulmonary thromboembolism was made tentatively on the basis of results of a radionuclide lung perfusion scan and was confirmed by exploratory thoracotomy and lung biopsy. Tachypnea and pleural effusion gradually resolved without specific treatment, and additional episodes of anemia or dyspnea have not been observed. The pathogenesis of these findings was suspected to be related to corticosteroid induced thrombotic tendencies, persistent thrombocytosis (greater than 800,000 cells/microliters), and vascular injury caused by repeated jugular venous catheterization. Pulmonary thromboembolism should be considered in dogs that develop clinical signs of tachypnea and/or pleural effusion during administration of immunosuppressive dosages of corticosteroids. PMID- 2599963 TI - Ehrlichiosis in a dog with seizures and nonregenerative anemia. AB - Ehrlichia canis infection was diagnosed in a dog with a history of seizures and nonregenerative anemia. Serologic titer to E canis was greater than 1:100. Evaluation of CSF revealed a high cell count, high protein concentration, and a positive Pandy test result. Several mononuclear leukocytes in the CSF contained E canis morulae. Central nervous system lesions are commonly found on postmortem examination of animals with ehrlichiosis, although clinical reports of neurologic signs attributable to this disease are less common. Ehrlichiosis should be included in the differential diagnosis of CNS disease in dogs from enzootic areas. PMID- 2599964 TI - Dermal necrosis associated with Rocky Mountain spotted fever in four dogs. AB - Four dogs with Rocky Mountain spotted fever developed extensive dermal necrosis. Factors contributing to this complication included delay in initiation of appropriate therapy. PMID- 2599965 TI - Multilobular osteochondrosarcoma of the canine skull: 16 cases (1978-1988). AB - The medical records of 12 dogs with multilobular osteochondrosarcoma (MLO) and examined at the Veterinary Teaching Hospital, Colorado State University from August 1979 to January 1987 were reviewed. Medical records of 1 dog with MLO and 3 dogs with MLO examined at the Ontario Veterinary College, University of Guelph and the Veterinary Medical Teaching Hospital, University of California, Davis, respectively, were also reviewed and included in the study. The mean age of affected dogs was 7.5 years, a single breed did not appear to be overrepresented, and males were affected as frequently as were females. All of the primary lesions affected either the mandible, maxilla, or cranium. Excision was the only treatment in 11 dogs, 2 dogs had radiotherapy in addition to excision, and 1 dog had radiotherapy and chemotherapy after excision. Twelve treated dogs had follow up information available. Of the 12 treated dogs, 7 (58%) had local recurrence, with median time to recurrence of 14 months. Seven dogs (58%) developed metastatic disease after treatment, with median time to metastasis of 14 months. The median disease-free interval was 12 months, and the median survival time was 21 months. Excision with histologically complete surgical margins appeared to offer good opportunity for long-term tumor control. The role of adjuvant chemotherapy and radiotherapy in the management of MLO remains unclear. PMID- 2599966 TI - Employment of 1989 male and female graduates of US veterinary medical colleges. PMID- 2599967 TI - What is your diagnosis? Probable neoplasm of the rostral portion of the mandible. PMID- 2599968 TI - What is your diagnosis? Scapulohumeral luxation. PMID- 2599969 TI - Size and management effects on reproduction in first-, second- and third-parity beef cows. AB - The effects of size, management and size x management interactions on reproduction in beef cattle were determined by using 3,126 breeding and calving records from 1980 to 1985. Cows were from three synthetic lines that differed in mature size (small, medium and large). The lines differed also in the percentages of Jersey, Angus and Simmental. Each line was replicated in two herds. One herd (Rhodes) followed a spring calving schedule and weaned calves at about 180 d of age. The other herd (McNay) calved cows in the fall and weaned calves early at about 45 d of age. Cycling rate, conception rate, abortion rate and calving rate were each evaluated for first-, second- and third-parity dams. An important interaction (P less than .05) was found between lines and management in heifers. Cycling rate and calving percentage were almost identical for all three lines in the Rhodes herd, but small heifers in the McNay herd had about 20% higher cycling (83.8 vs 63.1%) and calving rates (73.8 vs 53.0%) than large heifers. Line x management interactions were not significant in second- and third-parity dams, but line did remain a significant source of variation in calving rate. Calving rates in second-parity dams were 85.0, 78.1 and 70.7% for small, medium and large cows, respectively. In third-parity dams, small cows had a higher calving rate (P less than .05) than either medium or large cows (80.9 vs 66.1 or 68.7%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2599970 TI - Computer modeling of sheep reproduction: I. An algorithm for quantifying anestrous cycles in ewes. AB - An algorithm that mathematically describes annual estrous activity in ewes is given. The function fitted as the ordinate is similar to a normal distribution function related to date as the abscissa. The data used were collected from literature on different breeds and from different locations of the world; all studies had been specifically conducted to study estrous activity in ewes in these locations. Parameters estimated in an iterative procedure from the algorithm were length of time during which estrous cycles occurred (SA), a measure of asymmetry (SD), day of mid-estrous (DE), highest incidence of estrus (MX) and lowest incidence of estrus (MN), day of lowest incidence of estrus (DN) and day of mid-anestrous season (DA). Incidence of estrus is defined as the proportion of ewes exhibiting an active estrus. These parameters were estimated for several breeds and locations. The data, as collected, were inadequately cross classified to allow for unconfounded estimation. However, analyses of fitted parameters that describe the curves gave quantitative results about the influences of breed of sheep, location, latitude and altitude and indicated which parameters were associated with these factors. Breeds differed significantly for SA, DE, MX and DA. Locations differed for DE, MX and DA. Latitude was associated with differences in DE, DN and DA with altitude also associated with differences in DE and DA. There were no significant effects on SD even though breeds differed sizably in SD. PMID- 2599971 TI - Computer modeling of sheep reproduction: II. Accelerated reproduction in sheep. AB - A computer simulation program was written in SLAM (Simulation Language for Alternative Modeling) to simulate certain biological aspects involved in alternative systems of reproduction in sheep. Four fundamental lambing schemes, once a year, three times in 2 yr, twice a year and continuous schemes, along with modifications of these schemes, are simulated. Parameters of greatest effect in this simulation were the average spread of the estrous season (SA), the measure of asymmetry (SD) and the maximum proportion of ewes exhibiting estrus (MX). It was demonstrated that the greater the SA values (longer estrous seasons and shorter anestrous seasons), the more advantageous it was to breed frequently. The SD and MX parameters influenced to a lesser degree the lambing results obtained from these simulations. The relative merits of certain breeds and locations for out-of-season breeding were studied and evaluated for annual and seasonal fertility. PMID- 2599972 TI - Glucocorticoids and the differentiation of porcine preadipocytes. AB - The function of glucocorticoids in the differentiation of porcine preadipocytes was examined. Stromal-vascular cell cultures (containing preadipocytes) derived from adipose tissue of the perirenal, ham and shoulder regions of neonatal pigs were incubated in the presence of hydrocortisone at 0 to 100 ng/ml medium. Perirenal cells did not respond to hydrocortisone with an increase in enzyme expression, nor did they demonstrate growth characteristics similar to those of cultures derived from the ham or shoulder. Cultures from the shoulder and ham regions demonstrated dose-responsive increases in enzymatic expression to hydrocortisone. Enzymatic responses by cultures derived from the ham region were lower than responses by cultures from the shoulder region as measured by changes in the activities of sn-glycerol-3-phosphate dehydrogenase and lipoprotein lipase. Addition of insulin to the medium did not produce a synergistic effect with glucocorticoid on differentiation as determined by these enzymatic parameters. However, [14C]glucose metabolism by the cells in culture was synergistically increased by insulin and glucocorticoid supplementation of the medium. The ability of hydrocortisone to induce differentiation of porcine preadipocytes in vitro suggests that the changes that occur in plasma glucocorticoid concentrations during late gestation may play an important role in the rapid development of s.c. adipose tissue in the fetal pig. Secondly, the differences in culture characteristics and hormone responses of cells derived from different locations of adipose tissue formation indicate that differences may exist in the regulation of the growth and development of preadipocytes from different anatomical locations. PMID- 2599973 TI - Effects of recombinant DNA-derived somatotropin and dietary energy intake on development of beef heifers: I. Growth and puberty. AB - The effects of dietary energy intake and somatotropin (STH) on growth and puberty were studied in 40 Angus heifers. At an average age of 7 mo (208 +/- 8 d), heifers were assigned to four treatment groups: 1) vehicle (V) + high energy (HE; 2.68 Mcal ME/kg DM), 2) recombinant DNA-derived STH (20.6 mg/d; s.c.) + HE, 3) V + low energy (LE; 2.22 Mcal ME/kg DM) or 4) STH + LE. Animals remained on treatments until 15.5 mo of age. Body weights (BW), hip heights (HH) and areas of pelvic openings (PA) were measured every 28 d and backfat thicknesses (BF) were measured every 56 d. Plasma progesterone was measured in blood samples taken three times per week beginning at 9 mo of age to determine age at first ovulation. Heifers fed HE were heavier (P less than .01), gained faster (P less than .01) and had greater BF (P less than .01) than those fed LE. Animals treated with STH gained faster (P less than .01) and were heavier (P less than .05) between 12 and 15 mo of age than V-treated heifers. Heifers treated with STH also had less BF (P less than .05) and a tendency for a greater (P = .08) increase in HH than in V-treated heifers. Somatotropin interacted with energy (P less than .05) and age (P less than .01) to influence PA. Somatotropin increased (P less than .01) PA in heifers fed the HE diet but not in those fed the LE diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2599974 TI - Skeletal muscle protein synthesis and growth hormone secretion in young lambs treated with clenbuterol. AB - To determine effects of clenbuterol (CB) on muscle protein turnover and growth hormone (GH) secretion, 16 crossbred wether lambs (14.4 kg) were randomized into two groups designated to receive daily oral boluses of gelatin capsules containing corn starch with either 0 (control, CTL) or 1.87 mg/kg body weight CB for either 14 (n = 8) or 28 d (n = 8). This calculates to be approximately 40 mg CB/kg diet. Lambs had ad libitum access to a 16% crude protein corn-soy diet and feed consumption (FC) was measured. After 14 and 28 d, lambs were slaughtered and semitendinosus (ST), longissimus (LD) and brachialis (BR) muscles were exercised, weighed and analyzed for protein (TP) content. For 6 h prior to slaughter of 28-d lambs, 2.5 microCi L-[U-14C]tyrosine/kg was infused intravenously, blood was sampled and plasma was analyzed for specific radioactivity of tyrosine. Plasma GH concentrations were assessed by radioimmunoassay. No differences due to treatment were found in FC, rate of gain or GH concentrations. Semitendinosus and BR weights of control lambs at 14 d did not differ between treatments. At 28 d, ST and BR weights of control lambs (58.8 and 18.5 g, respectively) were less (P less than .10) than those of lambs treated with CB (74.3 and 23.1 g, respectively). The TP per ST and BR at 28 d for control lambs was 71.5 and 85.1% (P less than .10) that of muscles of lambs treated with CB. Fractional protein synthesis rates (FSR) of the BR (9.4 vs 6.1%/d) and total protein synthesized in ST muscle per day (1.4 vs .8 g) were elevated (P less than .10) in lambs treated with CB compared to controls. These data suggest that the increased fractional accretion rate observed in lambs treated with CB for 28 d was caused by increased FSR. PMID- 2599975 TI - Voluntary consumption and digestion of diets high in endophyte-infected fescue by growing Holstein steers. AB - Holstein steers (112 to 258 kg BW) were fed diets high in endophyte-infected fescue (80 to 100%) in 15 latin square experiments to determine the relationships among BW, forage composition, voluntary consumption and digestion. Fescue DM intake (kg/d) increased linearly (P less than .05) with increasing BW (-.513 + .0275 BW; R2 = .69). Regressing log fescue intake (DM) on log BW resulted in a BW exponent of 1.1034 (R2 = .66) but did not account for any more variation in intake than the simple regression did. The percentage NDF in fescue was not related (P greater than .10) to fescue intake (kg/d) and was correlated only slightly with fescue intake as a percentage of BW (r = -.13; P less than .10). Adding the percentage of fescue in the diet or NDF in the fescue to the regression of DM intake on BW did not increase explained variation. Organic matter intake (kg) and digestibility (%) were not related (P greater than .10). Based on standardized partial regression coefficients, differences in voluntary intake accounted for 60% of the variation in the total quantity of OM digested, whereas differences in digestibility accounted for 40%. In conclusion, ingestibility of endophyte-infected fescue hay in relation to changing BW did not vary greatly. Concentrations of chemical constituents such as NDF and ADL in fescue were poorly correlated with feed consumption and digestibility. PMID- 2599976 TI - Effects of protein and carbohydrate sources on digestibility and digesta flow rate in weaned pigs fed a high-fat, dry diet. AB - Two trials were conducted to evaluate the effects of protein source (48% CP soybean meal or casein) and carbohydrate source (25% dextrose or 25% lactose) on digestibility and digesta flow rate in early-weaned pigs. Diets contained 10% crude soybean oil and were formulated to contain 3.5 g lysine, 2.3 g Ca and 2.0 g P per 1,000 kcal DE of diet. In Trial 1, nutrient digestibility was greater for older than for younger pigs. Apparent digestibilities for energy, DM, CP and fat were lower (P less than .08) for younger and older pigs fed soybean meal rather than casein. Digestibility of soluble carbohydrates was less (P less than .02) for younger pigs fed soybean meal rather than casein as a protein source. Fat digestibility was lower (P less than .05) in younger pigs fed dextrose than in pigs fed lactose. A protein X carbohydrate source interaction (P less than .01) existed for fat digestibility by older pigs. In Trial 2, pigs were euthanatized, and digestibilities anterior to the ileum and the colon (pre-ileal and pre-cecal) were determined. At the ileum, fat digestibility was lower (P less than .05) for pigs fed soybean meal, whereas CP digestibility was lower (P less than .05) for pigs fed either soybean meal or dextrose. A protein X carbohydrate interaction was observed for ileal digestibilities of DM (P less than .06) and total carbohydrates (P less than .03) with lowest values obtained for the soybean meal plus dextrose diet. For casein diets, digestibility values were similar between the two carbohydrate sources.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2599977 TI - Evaluation of a biological response modifier: effects on starter pig performance. AB - The influence of a biological response modifier (FK-565) on weanling pig performance was evaluated. One hundred twenty-five weanling pigs (weaned at 21 +/ 3 d) averaging 6.3 kg were utilized in a 35-d growth trial. Dietary treatments included a basal diet (1.25% lysine, corn-soybean meal-dried whey), the basal plus .1, 1 or 10 ppm FK-565 and the control plus an antibacterial combination containing chlortetracycline, sulfamethazine and penicillin. Performance was recorded weekly, and on d 35 all pigs were bled for whole blood and serum chemistry profiles and then were euthanatized. Heart, liver, kidneys and spleen weights were recorded. Also, gross and histological examinations were made of these organs, as well as sections of lung, ileum, bone marrow, thymus and mesenteric lymph node. By d 14, pigs fed the antibacterial diet gained faster (P less than .06) than pigs fed the control and FK-565 diets. However, no differences (P less than .10) in feed intake at d 14 or efficiency of feed utilization at either d 14 or 35 were observed. For the overall 35-d trial, ADG was greater (P less than .01) for pigs consuming the antibacterial diet than for pigs consuming control and the FK-565 diets. Pigs consumed more of the antibacterial diet than of the other diets (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2599978 TI - Relationship between uterine secretion of prostaglandin F2 alpha induced by oxytocin and endogenous concentrations of estradiol and progesterone at three stages of the bovine estrous cycle. AB - The purpose of this experiment was to determine whether differences among cows in the ability of oxytocin to stimulate uterine secretion of prostaglandin F2 alpha (PGF2 alpha) were related to the endogenous ovarian steroid environment. Sexually mature heifers were treated with oxytocin (.33 IU/kg BW) at three stages of the estrous cycle: early (d 3 to 5; n = 5), middle (d 10 to 11; n = 5) or late (d 16 to 17; n = 5). To assess uterine responsiveness to oxytocin, concentrations of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were quantified in jugular venous plasma samples collected at 1/2-h intervals for 8 h postinjection. The ovarian steroid environment at the time of injection was estimated by measuring the concentrations of progesterone and estradiol in jugular venous plasma samples collected at 4-h intervals for 12 h immediately prior to injection. Concentrations of PGFM increased immediately following injection of oxytocin either early or late in the estrous cycle. The response was much less during the middle of the estrous cycle. The magnitudes of response, early and late in the estrous cycle, were similar and greater than that observed during the middle of the estrous cycle (P less than .05). There was a positive relationship (R2 greater than .8; P less than .05) between magnitude of the response to oxytocin and ratio of estradiol to progesterone both early and late in the estrous cycle. Thus, individual differences in uterine secretion of PGF2 alpha in response to oxytocin were related to stage of the cycle and to differences in the endogenous ovarian steroid environment within each stage of the estrous cycle. PMID- 2599979 TI - Effects of monensin and pH on the production and utilization of pyro-glutamate, a novel product of ruminal glutamine deamination. AB - Pure cultures of monensin-sensitive ruminal bacteria were involved in both the production and utilization of pyro-glutamate (pyrrolidone carboxylic acid), a novel product of glutamine fermentation, but the effect of monensin on pyro glutamate accumulation in mixed cultures had not been assessed. Mixed ruminal bacteria (n = 3) fermented glutamine (40 mM) at a rapid rate (63 nmol/[mg protein min]) and there was a transient increase in pyro-glutamate (3 mM). Monensin (5 ppm) decreased the rate of glutamine fermentation 70% and greatly enhanced the conversion of glutamine to pyro-glutamate (50 vs 7%). Glutamate was fermented at nearly the same rate as glutamine, and monensin eliminated glutamate fermentation. Glutamate was never converted to pyro-glutamate. Trypticase, a pancreatic digest of casein, contained pyro-glutamate, and a significant fraction (30%) of its N was never converted to ammonia. Pyro-glutamate utilization was reduced by monensin and low pH (less than 6.0). Based on these in vitro observations, pyro-glutamate could be a significant end-product of glutamine degradation when animals are fed monensin. PMID- 2599980 TI - Physiological responses of cattle consuming tall fescue to environmental temperature and supplemental phenothiazine. AB - The influence of supplemental phenothiazine (P) on growth and physiological criteria was studied in parasite-controlled calves consuming endophyte (Acremonium coenophialum)-infected tall fescue (TF). In Exp. 1, nine Angus heifer calves (312 kg) were supplemented with 227 g corn-mineral (CM) mix twice daily and allowed ad libitum access to either high-endophyte (HE) G1-307 (greater than 90% infected) or low-endophyte (LE) Kenhy (less than 1% infected) tall fescue hay, or HE G1-307 plus 2 g/d P in the daily supplement. Calves were kept in temperature-controlled rooms for 12 d at 21 degrees C followed by 7 d at 34 degrees C. In Exp. 2, 48 Angus steer calves (312 kg) were assigned to treatment groups consisting of calves grazing HE Kentucky-31 (57% infected) or LE Johnstone (less than 1% infected) TF, and supplemented daily with either .91 kg of a control CM mix or .91 kg of the CM mix containing 2 g P. The 112-d experiment was initiated on May 4 with BW and rectal temperature (RT) measurements and blood collected at 28-d intervals. In both experiments, calves receiving HE TF had lower (P less than .01) serum prolactin concentrations (PRL) at elevated ambient temperature and lower (P less than .01) serum alkaline phosphatase activities (AP) but higher (P less than .01) RT than calves consuming LE TF regardless of ambient temperature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2599981 TI - Alteration of nitrogen metabolism by alpha-ketoglutarate administration in growing lambs fed high nonprotein nitrogen-containing diets. AB - Two completely randomized design experiments were conducted, using either 10, 38 kg (Exp. 1) or 10, 26-kg (Exp. 2) Hampshire x Western wether lambs, to study the effects of alpha-ketoglutarate (AKG) administration on N metabolism. Lambs were fed 890 and 885 g DM/d in Exp. 1 and 2, respectively, of corn-cottonseed hull basal diets with urea added to attain CP levels of 10.6 and 10.5% in Exp. 1 and 2, respectively. Experiments consisted of 10 d of adaptation followed by 7 d of infusion and excreta collection. Lambs were infused continuously either i.v. (Exp. 1) or abomasally (Exp. 2) with control solutions (CON) or solutions containing 41.3 g AKG/d (AKG). In Exp. 1, fecal and urinary N excretion and N retention were not affected (P greater than .10) by treatment. Compared to CON in Exp. 2, AKG infusion increased (P less than .10) fecal N output (6.6 vs 5.9 g N/d) but did not affect (P greater than .10) the amount of N retained (4.4 vs 3.5 g N/d). Compared to CON, AKG increased (P less than .10) urinary NH3 N excretion in Exp. 1. Serum urea N was lower (P greater than .10) for AKG than for CON in Exp. 1 but was not affected (P greater than .10) by treatment in Exp. 2. In Exp. 1, AKG appeared to reduce activities of several serum enzymes that function in amino N metabolism. In Exp. 1, compared to CON, AKG decreased (P less than .10) aspartate but increased (P less than .10) asparagine in serum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2599982 TI - Ionophores alter hepatic concentrations of intermediary carbohydrate metabolites in steers. AB - The effects of ionophores on liver weight and function were determined in finishing steers (n = 24; avg weight 440 kg). Steers were group-fed one of three treatments (control, lasalocid or monensin at 33 mg/kg feed) for 46 d prior to slaughter. Three days prior to slaughter, blood was collected for the determination of serum Ca and Mg. At slaughter, the liver was removed, weighed, sampled, frozen in liquid nitrogen and subsequently analyzed for concentrations of carbohydrate metabolites and minerals. Liver weight (5.9 kg) was unaffected by treatment. Serum and hepatic Ca and Mg were not affected by ionophore treatment. Hepatic glycogen levels in steers fed ionophores were unaffected by treatment. Fructose 1,6-bisphosphate was 21% lower (P less than .10) in hepatic tissue of steers fed ionophores, whereas dihydroxyacetone phosphate was 15 to 37% greater in hepatic tissue of steers fed monensin (P less than .20) or lasalocid (P less than .10). Glyceraldehyde 3-phosphate was elevated more extensively by lasalocid than by monensin with increases of 72 (P less than .05) and 132% (P less than .001), respectively, over controls. Glycerol 3-phosphate levels were 37% (P less than .05) and 12% (NS) greater with these ionophores. Hepatic levels of pyruvate were elevated 12 (NS) to 36% (P less than .17) for monensin and lasalocid. Fructose 2,6-bisphosphate levels were 25% lower (P less than .25) in hepatic tissue of steers fed ionophores than in hepatic tissue from control steers. Other metabolites of carbohydrate metabolism in hepatic tissue were not altered appreciably. Changes in levels of intermediary metabolites of carbohydrate metabolism suggest alterations in hepatic carbohydrate metabolism favoring gluconeogenesis in steers fed ionophores. PMID- 2599983 TI - The metabolism of 75Se-selenomethionine in sheep given supplementary copper and molybdenum. AB - Four groups of three ram lambs were fed, in group pens, the following diets from 4 to 19 wk of age: 1) control (6 mg Cu/kg and 1 mg Mo/kg); 2) control plus 10 mg Cu/kg; 3) control plus 10 mg Mo/kg and 4) control plus 10 mg/kg of both Cu and Mo. Copper and Mo were added to the diet as copper sulfate and sodium molybdate. The main ingredients of the diets were alfalfa hay (20%), oats (20%) and corn (59%). At 19 wk, the animals were allocated randomly to individual metabolism cages and received a single oral dose of 75Se-selenomethionine. Liver Cu concentrations at slaughter (22 wk) were 77, 259, 68 and 316 mg/kg fresh weight for treatments 1 through 4. There was clinical evidence of Cu poisoning in lambs on treatment 2. Sheep given Cu supplements without additional Mo had reduced (P less than .05) levels of 75Se activity in muscle compared with control animals. This decrease in muscle 75Se in Cu-supplemented lambs was associated with a nonsignificant increase in 75Se content of other tissues and a nonsignificant increase in fecal excretion of 75Se. Apparent absorption and net retention of 75Se was 80% and 74%, respectively. Long-term ingestion of moderate levels of Cu influenced the metabolism of Se fed as selenomethionine, possibly through effects of chronic Cu toxicity on liver function. PMID- 2599984 TI - Estimation of the relative bioavailability of manganese sources for sheep. AB - The relative biological availability of Mn in reagent-grade (RG) Mn sources was tested using 41 Rambouillet crossbred wether lambs in a completely randomized design. Lambs were fed a basal corn-soybean meal-cottonseed hull diet (37.6 ppm Mn, DM basis) or this basal diet supplemented with 0, 1,500, 3,000 or 4,500 ppm Mn from RG MnSO4.H20 or 3,000 ppm Mn from RG MnO, MnO2 and MnCO3. Feed intake was restricted to 1,000 g/hd daily during the 21-d experimental period. There was a decrease (P less than .01) in daily feed intake by sheep fed 4,500 ppm Mn from MnSO4. Liver, kidney and bone Mn concentrations increased (P less than .05) with MnSO4 supplementation. Liver was most responsive to dietary Mn, followed by kidney and bone. Based on multiple linear regression slopes for liver, kidney and bone Mn concentrations, relative bioavailability of Mn from MnO, MnO2 and MnCO3 averaged 57.7, 32.9 and 27.8%, compared with 100% for MnSO4. PMID- 2599985 TI - Insulin-like growth factor 1 induction of differentiation of porcine preadipocytes. AB - The role of insulin-like growth factor I (IGF-1) in the development of the porcine preadipocyte was studied. Primary cultures of stromal-vascular cells (containing preadipocytes) were derived from s.c. adipose tissue of pigs at 1 d of age by enzyme digestion and centrifugation. Cells were cultured for a total of 15 d. Cells were exposed to IGF-1 at concentrations of 0, 5, 25 or 50 ng/ml medium during one of four time periods: d 1-15, d 1-5, d 13-15, or 4 h on d 15 of culture. IGF-1 had a mitogenic effect on cells during the first three time periods as determined by coulter counting. IGF-1 induced the enzymatic differentiation of porcine preadipocytes following exposure for either the entire 15 d of culture or for only 48 h (d 13-15) after confluency had been attained (d 5). Histochemically, lipid accumulation over time paralleled changes in enzyme activity. Incubation of IGF-1 with the cell cultures during the logarithmic phase of growth (d 1-5) or for 4 h on d 15 did not affect enzyme activity. These data indicate that IGF-1 can induce the differentiation of porcine preadipocytes after the cells leave the logarithmic phase of growth through action on post-confluent events. PMID- 2599986 TI - Influence of gender, breed and age on maturity characteristics of sheep. AB - Fifty-one ewes, 50 wethers and 51 rams of Finn x whiteface or Suffolk x whiteface breeding were slaughtered at an average age of 271, 361, 459, 557 or 652 d to study changes in maturity characteristics with changes in age. When metacarpal epiphyseal cartilage (growth plates) ossifies with age, break joints on the distal end of the metacarpals fuse and the end of the bone then appears as a spool joint rather than as a break joint. This fusion occurs earlier chronologically in ewes than in rams or wethers. Most Finn x whiteface-cross ewes, which normally reach reproductive maturity earlier than Suffolk x whiteface cross ewes, exhibited ossified metacarpal growth plates by 459 d of age; break joints of Suffolk x whiteface crosses were not fused until 557 d of age. Both breed groups of rams exhibited fused joints by 557 d of age, but only 3 of 10 wethers exhibited spool joints at 652 d of age. Microscopic examination showed that even in these three wethers the epiphyseal growth plate could still be detected. Yearling 2-yr-old classifications of sheep from teeth were not gender dependent within the discrete age classes of this study. About half the sheep in each gender group were classified as yearlings at 459 d of age and about half in each group were classified as 2-yr-olds by 652 d of age. Stepwise multiple regression equations to estimate age of sheep in days were developed. Overall maturity, lean color and texture and rib bone maturity were the best carcass measures of maturity. Maturity scores for characteristics of the break joint did not enter any of the equations studied. When eye lens weight was included in equations with the best measures of carcass maturity, accuracy of estimates for age of sheep was improved. PMID- 2599987 TI - Perspectives on dental health, Part V: 1988 Hawaii State Department of Health's Dental Practice Survey. PMID- 2599988 TI - Dietary fluoride supplements for Hawaii's children--the role of the dentist. PMID- 2599990 TI - An increase in the antimicrobial activity in vitro of fosfomycin under anaerobic conditions. AB - Fosfomycin showed lower MIC values under anaerobic culture conditions than those under aerobic conditions for four Gram-positive and 18 Gram-negative bacterial isolates. The degree of change in MICs was dependent on the culture media and strains tested. The growth-inhibitory diameter in the paper disc assay increased in parallel with the decrease in the redox potential of the agar medium. Bacteriolytic activity was also potentiated in anaerobiosis. The increase of the bio-activity of fosfomycin in anaerobic culture was neither due to the change of medium pH nor to the change of mobility of drug in agar. However it is possible that the uptake of fosfomycin through the cell membrane increased in anaerobiosis. The anaerobic MICs of fosfomycin were better correlated than the aerobic MICs with the ED50 values in a mouse systemic infection model. PMID- 2599989 TI - Emergence of methicillin-resistant clones from cephamycin-resistant Staphylococcus aureus. AB - Staphylococcus aureus strains specifically resistant to cephamycin antibiotics have been found among recent clinical isolates. These strains formed penicillin binding protein (PBP) 2' and became phenotypically resistant to methicillin after induction with cefoxitin. Other cephamycin-type antibiotics also induced methicillin-resistance, whereas non-cephamycin-type cephalosporins such as cefmenoxime and ceftizoxime did not do so. The clones that constitutively synthesized PBP 2' arose from the cephamycin-resistant strains at a frequency of 10(-5). They were indistinguishable from clinically isolated methicillin resistant S. aureus (MRSA). Cephamycin-resistant S. aureus may be a source for emerging MRSA. PMID- 2599991 TI - Comparative in-vitro activity of twenty antimicrobial agents against clinical isolates of Mycobacterium avium complex. AB - The in-vitro susceptibility of Mycobacterium avium complex isolates, obtained from immunosuppressed patients with and without the Acquired Immunodeficiency Syndrome (AIDS), to various antimicrobial agents was determined. Amikacin, the 4 quinolone compounds--ciprofloxacin, temafloxacin and PD 117558--and the penem SCH 34343 were active against most of the isolates. In-vitro synergism using selected antimicrobial combinations could not be demonstrated. No differences in the susceptibility, depending upon the source of the isolates (AIDS or non-AIDS), were noted. PMID- 2599992 TI - In-vitro susceptibility of the Bacteroides fragilis group and the inoculum effect of newer beta-lactam antibiotics on this group of organisms. AB - The susceptibility and inoculum effect of 190 selected Bacteroides fragilis group isolates were determined with six beta-lactam antibiotics by two different methods: agar dilution and broth microdilution. The results were analysed by species within this group of pathogens. The evaluation showed that imipenem had superior activity and was very stable to increased inoculum concentration. Cefoxitin and piperacillin exhibited very good activity and very small inoculum effect; latamoxef showed stability to changes in the inoculum concentration but only intermediate activity; while ceftizoxime and cefoperazone exhibited a marked inoculum effect and relatively poor activity. Resistance among the species was as follows: B. distasonis greater than B. thetaiotaomicron greater than B. ovatus greater than B. fragilis. The inoculum effect was higher when tests were performed in broth rather than in agar. In general, the effect was more pronounced among B. ovatus and less among B. distasonis isolates. PMID- 2599993 TI - Mechanisms of gentamicin resistance in gram-negative bacilli in Riyadh, Kingdom of Saudi Arabia. AB - A survey was undertaken of the prevalence and mechanisms of gentamicin resistance in Gram-negative bacilli in Riyadh. Gentamicin resistance, as assessed by the Stokes method, occurred in less than 2% of isolates of Escherichia coli, about 10 25% of most other enterobacteria, about 40% of Acinetobacter spp. and about 25% of Pseudomonas aeruginosa. This finding of relatively low rates of gentamicin in Enterobacteriaceae was surprising in view of the unregulated use of antibiotics until recent years. AAD(2'') was by far the most commonly detected aminoglycoside modifying enzyme in the enterobacteria. However Providencia spp. always produced AAC(2') and there was an association between Serratia spp and AAC(6'). Enzymes were less frequently detected in Acinetobacter spp. and Pseudomonas spp. AAD(2'') was also the most common enzyme in Pseudomonas spp. but was never found in Acinetobacter spp. Non-enzymatic resistance played an insignificant role in the resistance of Enterobacteriaceae in Riyadh, but may be more important in Pseudomonas spp. PMID- 2599994 TI - The changing pattern of antibiotic susceptibilities of Bacteroides fragilis in Kuwait. AB - The susceptibility of 340 distinct strains of Bacteroides fragilis isolated during 1981 to 1988, to eight antimicrobial agents was determined. These included isolates from infected hospitalized patients (127), infected out-patients (89), faecal isolates from uninfected patients hospitalized for greater than 10 days (48) and from normal subjects in the community (76). All strains were susceptible to metronidazole with a MIC of 1 mg/l. The least effective antibiotics were ampicillin, fusidic acid, erythromycin and tetracycline. There was no significant difference in antibiotic sensitivities between strains causing community-acquired and those causing hospital-acquired infections. However faecal isolates from hospitalized patients were significantly more resistant to ampicillin (P less than 0.05), cefoxitin (P less than 0.005) and clindamycin (P = 0.001) than community faecal isolates. During the study period there was a rise in resistance to clindamycin (P less than 0.005), cefoxitin, erythromycin and fusidic acid (P less than 0.001) and tetracycline (P less than 0.05). Antimicrobial resistance of B. fragilis is rising and long periods of hospitalization seem to play an important role in its development. PMID- 2599995 TI - Penetration of antibiotics into bovine neutrophils and their activity against intracellular Staphylococcus aureus. AB - The penetration of three antibiotics, penicillin, chloramphenicol and erythromycin into bovine neutrophils, either alone or containing previously ingested Staphylococcus aureus, was determined, and their intracellular activity against these bacteria was measured. Uptake of radiolabelled antibiotics was assessed by rapidly separating neutrophils from extracellular antibiotic by centrifugation through silicone oil. Intracellular activity was estimated by comparing the numbers of bacteria surviving intracellularly in neutrophils exposed to antibiotic for 3 h at ten times the MBC, with those surviving intracellularly in untreated neutrophils. Penicillin was slightly concentrated within the neutrophils, reaching a maximum intracellular concentration 1.75 times that of the extracellular concentration; this is the C/E ratio. Chloramphenicol entered to a greater extent with a maximum C/E ratio of 7.08. Erythromycin became highly concentrated within the neutrophils with a C/E ratio of 11.46 after 90 min incubation. The presence of ingested staphylococci significantly reduced the uptake of chloramphenicol, but had no significant effect on the penetration of the other antibiotics. Intracellular activity studies indicated that, at ten times MBC, only penicillin had any significant activity against intracellular staphylococci, reducing survival by 28%. This work demonstrates that penetration of certain antibiotics can be altered by the presence of ingested staphylococci and that high intracellular levels of antibiotics do not necessarily ensure good intracellular activity against pathogenic micro-organisms. PMID- 2599997 TI - Elimination of cefuroxime and gentamicin during and after open heart surgery. AB - In eight consecutive adult heart surgery patients, serum concentrations of cefuroxime and gentamicin were studied during and after operation. Repeated doses of cefuroxime 1.5 g and gentamicin 80 mg were given. Intra-operative concentrations were deemed adequate (cefuroxime Cmin: 16-45 mg/l, gentamicin Cmin: 1.6-2.8 mg/l), and no differences (P = 0.05) could be demonstrated between elimination rates during and after open heart operation (cefuroxime T1/2 101 vs 111 min, gentamicin T1/2 191 vs 193 min). PMID- 2599996 TI - Penetration of macrolides into human polymorphonuclear leucocytes. AB - Five 14C-labelled macrolide antibiotics (erythromycin, josamycin, clarithromycin (TE-031), rokitamycin and roxithromycin) were studied for their transport into human polymorphonuclear leucocytes. Intracellular/extracellular concentration ratios (transport ratios) of these macrolides were quite high: erythromycin, 6.6; josamycin, 15.5; clarithromycin, 16.4; rokitamycin, 30.5; and roxithromycin, 21.9. When polymorphonuclear leucocytes were pre-treated with formaldehyde or incubated at 4 degrees C, or at low pH, transport ratios were reduced. When extracellular macrolide was removed, intracellular macrolide concentrations became as low as 30% of the pre-wash concentrations in 5 min. KF lowered the transport ratios of josamycin and rokitamycin in particular and NaCN reduced the transport ratios of erythromycin and josamycin strikingly. Ouabain slightly lowered transport ratios of all the antibiotics tested except roxithromycin, and 2, 4-dinitrophenol decreased the transport ratio of clarithromycin markedly. The addition of various amino acids or hexose did not inhibit the transfer. Adenosine, however, inhibited the transfer of these antibiotics except erythromycin and lowered transport ratios by 83 to 92%. Puromycin reduced transport ratios of the same antibiotics by 59 to 95%. With polymorphonuclear leucocytes that had phagocytosed Legionella pneumophila serogroup 1, transport ratios of all five drugs tended to decrease. However, when Staphylococcus aureus ATCC 25923 or opsonized zymosan was phagocytosed, transport ratios for macrolides, except for roxithromycin, increased. PMID- 2599998 TI - Clinical and pharmacokinetic aspects of ciprofloxacin in the treatment of acute exacerbations of pseudomonas infection in cystic fibrosis patients. AB - Twelve cystic fibrosis patients, aged over 18, who had developed an acute respiratory exacerbation and who had Pseudomonas species isolated from their sputum, were entered into a clinical trial involving ciprofloxacin. The dosage regimen was 100 mg iv followed by 500 mg twice daily orally if less than 40 kg in weight and 200 mg iv followed by 750 mg twice daily orally if greater than 40 kg. Ciprofloxacin was well tolerated with no major side effects, except in one patient who withdrew after onset of headaches and generalized aches and pains. Eleven of the 12 patients showed clinical improvement at the end of the treatment period as determined by weight gain, Shwachman Score, Chrispin Norman Score and pulmonary function tests. MICs of Pseudomonas species isolated from the sputum at the start of the trial were in the range 0.25-4 mg/l. During therapy, sensitivity of isolates decreased and did not return to starting levels at the end of a four week follow-up period. Pharmacokinetic parameters were similar to those reported for fasting healthy volunteers by other workers except for bioavailability which was reduced in the non-fasting patients. PMID- 2599999 TI - Long-term accuracy of fluorescence polarization immunoassays for gentamicin, tobramycin, netilmicin and vancomycin. AB - External quality control was performed during six years to determine the accuracy over time of the Abbott TDx fluorescence polarization system for assaying antibiotics. Unknown spiked serum samples of gentamicin, tobramycin, netilmicin and vancomycin were provided monthly by the British national external quality assessment scheme. Comparison of the 209 assay results with the target concentrations showed good correlations in all four assays. No significant deviations from linearity, from slope 1.0, and from intercept 0.0 were detected by regression analysis. Relative deviations were less than 10% and less than 15% for 78% and 90% of all specimens, respectively. On an average the same calibration curves could be used over a period of 19 weeks. Fluorescence polarization immunoassays provided rapid and reliable results over the entire study period. PMID- 2600000 TI - Inactivation of aztreonam by faecal supernatants of healthy volunteers as determined by HPLC. AB - The enzymatic inactivation of aztreonam to its biologically inactive open ring form, by faecal enzyme preparations from 12 volunteers, was investigated. The percentage inactivation was determined by a high-performance liquid chromatography assay at months 0, 6 and 24. Faecal enzyme preparations from five volunteers could inactivate aztreonam by more than 50% within 20 h at one or more of these sampling times. Monitoring of aztreonam inactivation over a shorter period of time (14 days) in three of the volunteers showed that aztreonam inactivation cannot be predicted. PMID- 2600001 TI - Antibiotic exposure delays intestinal colonization by Clostridium difficile in the newborn. AB - Two antibiotic regimens commonly used in neonatal intensive care were compared for the rate at which Clostridium difficile appeared in the faeces. Over a nine month period neonates with suspected sepsis admitted to a Special Care Baby Unit (SCBU) were randomly allocated to receive either cefotaxime or penicillin and netilmicin. A contemporaneous group also admitted to SCBU but without sepsis served as non-treated controls. Four hundred and sixteen stool specimens from 158 neonates without diarrhoea were analysed every five to seven days until discharge. The results showed that these antibiotics did not encourage gut colonization by C. difficile, that they might even be protective in this respect and that monotherapy with cefotaxime was no more likely to generate C. difficile overgrowth than the penicillin-aminoglycoside regimen. PMID- 2600002 TI - Prevention of infection after vascular reconstruction. PMID- 2600003 TI - Susceptibility of staphylococci to paldimycin, and emergence of resistance, in vitro. PMID- 2600004 TI - Attitudes to use of rifampicin in non-tuberculous infections. PMID- 2600005 TI - Inhibition of endotoxin reactivity by aminoglycosides. PMID- 2600006 TI - Regional and temporal variation in canine peripheral lung responses to dry air. AB - Variation in dry airflow-induced broncho-constriction (AIB) in the canine lung periphery was examined using a wedged bronchoscope technique. Collateral system resistance (Rcs) was measured before and after dry-air challenge. Base-line Rcs was similar throughout the lung periphery, between dogs, and over time. Increasing base-line Rcs was correlated with increasing maximum Rcs 5 min postchallenge (Rcs5), increasing change in Rcs (dRcs5), and decreasing percent change in Rcs above base line (%Rcs5). In contrast to repeated challenge in which base-line Rcs was similar, the magnitude of AIB associated with consecutive challenges with unequal base lines depended on the parameter used to evaluate the response (i.e., Rcs5, dRcs5, or %Rcs5). Peripheral lung resistance then increased to a stimulus specific maximum regardless of base-line Rcs, although data expressed as %Rcs5 or dRcs5 may obscure this observation. Although a change in peripheral lung resistance does not necessarily imply airway narrowing, it is consistent with the idea that changes in Rcs are independent of the collateral system's resting tone. PMID- 2600007 TI - Immunoadjuvants enhance the febrile responses of rats to endogenous pyrogen. AB - The febrile responses of male Sprague-Dawley rats to a semipurified endogenous pyrogen produced from human monocytes were characterized by establishing fever dose-response curves. The animals were then injected intravenously with a number of substances that possessed the common properties of stimulating the phagocytic activity of the cells of the reticuloendothelial system and of acting as immunoadjuvants. The substances used were zymosan, lipopolysaccharide endotoxin, and muramyl dipeptide. Three days after any of these immunoadjuvants were injected, the fever sensitivity of the rats was remeasured. In each case, the slope of the fever dose-response curve tripled, and in some instances the response threshold for fever response was reduced by factors of three to eight. Furthermore, the maximum increase in body temperature produced by the endogenous pyrogen was more than doubled after immunoadjuvant treatment. By contrast latex beads, which are also phagocytized by the cells of the reticuloendothelial system but do not subsequently increase their phagocytic index nor do they enhance immune responses, had no effect on the fever sensitivity of rats in response to endogenous pyrogen. In the light of these findings, it is suggested that the febrile responses of rats to endogenous pyrogen are mediated in some manner by cells that possess some of the properties of reticuloendothelial cells. The location of these putative cells must be close to the circulation, because the immunoadjuvants used in this study were, for the most part, large molecular weight molecules that could not cross the blood-brain barrier easily. PMID- 2600008 TI - Enhancement of the febrile responses of rats to endogenous pyrogen occurs within the OVLT region. AB - The febrile responses of male Sprague-Dawley rats to a semi-purified endogenous pyrogen (EP) derived from human monocytes are markedly enhanced 3 days after the animals are intravenously injected with a variety of immunoadjuvants. The present study was designed to investigate the site within the body at which these substances act to produce this febrile-enhancing phenomenon. Stainless steel microinjection cannula guide tubes were implanted within the region of the organum vasculosum lamina terminalis (OVLT) of the rats and control febrile dose response curves to EP were established. Minute quantities of the immunoadjuvants zymosan, lipopolysaccharide endotoxin, and the synthetic adjuvant peptide, muramyl dipeptide, were microinjected into the OVLT region and 3 days later, the febrile responses of the animals were retested. In each case the febrile response elicited by a standard dose of EP was more than doubled, the slope of the fever dose-response curve was tripled, and the dose threshold was lowered by a factor of four to five. These responses are identical with those produced when much larger amounts of these immunoadjuvants are injected intravenously, and, thus, we conclude that the site of action of these substances in enhancing fever in response to EP resides in or near the OVLT region. It is proposed that EP stimulates a type of reticuloendothelial cell residing within the OVLT to release prostaglandin E, which in turn crosses the blood-brain barrier to effect the changes in the thermoregulatory neurons of the preoptic anterior hypothalamic area that result in fever. PMID- 2600009 TI - Sustained maximal ventilation after endurance exercise in athletes. AB - Although impaired respiratory muscle performance that persists up to 5 min after exercise is stopped has been demonstrated during exhaustive exercise in normal young men, it is not known whether impaired respiratory muscle function follows endurance exercise to exhaustion in highly trained athletes. To study the effects of exercise on sustained maximal voluntary ventilation immediately after exercise, eight elite cross-country skiers performed a 4-min maximal sustained ventilation (MSV) test before and immediately after exhaustive exercise. Subjects were encouraged to maintain maximal ventilation (VE) throughout the MSV test. To encourage greater effort, rapid visual feedback of VE was provided on a computer terminal along with a target VE based on their 12-s maximum voluntary ventilation (MVV). The subjects (7 males, 1 female) were 18.5 +/- 0.9 yr old (mean +/- SD) and exercised for 62.5 +/- 16.7 min at 77 +/- 5% of their maximum oxygen consumption during which average VE was 106.7 +/- 24.2 l/min BTPS. The mean MVV was 196.0 +/- 29.9 l/min or 107% of their age- and height-predicted MVV. Before exercise the MSV was 86% of the MVV or 176.7 +/- 30.5 l/min, whereas after exercise the MSV was 90% of the MVV or 180.3 +/- 28.9 l/min (P = NS). The total volume of gas expired during the 4-min MSV was 706.7 +/- 121.9 liters before and 721.2 +/- 115.5 liters after exercise (P = NS). In this group of athletes, exhaustive exercise produced no deleterious effects on the ability to perform a 4 min MSV test immediately after exercise. PMID- 2600010 TI - Nonadrenergic bronchodilation in adult and young guinea pigs. AB - The contribution of the nonadrenergic inhibitory system to airway responses to infusion of 5-hydroxytryptamine (5-HT) was evaluated in anesthetized, tracheotomized, and paralyzed young (13 days) and adult (82 days) guinea pigs. Animals were mechanically ventilated by a constant flow ventilator. Compliance (C) and conductance (G) of the respiratory system were continuously monitored. Three series of experiments were performed involving intravenous pretreatment with 1) atropine (3 mg/kg) and propranolol (1 mg/kg); 2) atropine (3 mg/kg), propranolol (1 mg/kg), and phentolamine (2 mg/kg); and 3) atropine (3 mg/kg) and hexamethonium (2 mg/kg). 5-HT was then intravenously infused for 5 min at a rate of 40 ng.kg-1.s-1 in adults and 60 ng.kg-1.s-1 in young guinea pigs to obtain the same degree of bronchoconstriction in both groups. At the 3rd min of the infusion, bilateral cervical vagotomy was performed and C and G were measured at the maximal response, 1-2 min thereafter. Vagotomy increased bronchoconstriction (P less than 0.01) in both young animals and adults. Phentolamine did not modify this increase, but hexamethonium completely inhibited it. These results indicate that, in adult and young guinea pigs, 5-HT infusion induces reflex activation of the nonadrenergic inhibitory system, which in turn modulates the bronchoconstrictor responses to 5-HT. This neural modulation is not mediated by an alpha-adrenergic pathway. PMID- 2600011 TI - Tissue glucose utilization during epinephrine-induced hyperglycemia. AB - The aim of this study was to investigate glucose utilization by individual tissues during epinephrine infusion. First, the applicability of the 2 deoxyglucose (2-DG) tracer technique during in vivo hyperglycemia was investigated in model systems in vitro. Epitrochlearis muscle and spleen cells were incubated with 1.25-20 mM glucose. The discrimination against 2-[14C]DG in glucose metabolic pathways, expressed by the lumped constant, remained unchanged over this wide range of glucose concentrations. It was concluded that in vivo hyperglycemia does not preclude the application of the 2-DG method. In a series of in vivo experiments, chronically catheterized conscious rats fasted for 24 h and were infused with epinephrine (0.2 microgram.kg-1.min-1), which produced a two-fold increase in plasma glucose concentration. 2-[14C]DG was injected 30 min after starting the epinephrine infusion and glucose utilization rates of individual tissues were calculated based on the concentration of phosphorylated 2 DG in samples excised at 70 min. The epinephrine infusion increased glucose utilization rates by 40-160% in hindlimb muscles, skin, ileum, liver, spleen, lung, epididymal fat, and kidney, although no change was found in the brain. Mass action of the increased plasma glucose is likely to play an important role in the enhanced rate of glucose utilization. PMID- 2600012 TI - Mechanical analysis of extrapulmonary volume displacements in the thorax and abdomen. AB - Currently, the effect of intrathoracoabdominal, extrapulmonary volume displacements (Vep) are not well understood. Various clinical conditions can lead to volume displacements caused by gas or liquid accumulations. To analyze the pressure and volume changes that occur by Vep, we used a mathematical model of chest wall and lung mechanics that accounts for static changes associated with rib cage, diaphragm, abdomen, and lungs. By solving the model equations, we obtained simulations of the pleural and abdominal displacements that clearly differentiate the mechanisms involved. When abdominal displacement occurs, the reduction in lung volume is less than that caused by an equal displacement in pleural space. Abdominal displacement produces an increased pressure that expands the rib cage significantly, whereas pleural displacement does not produce a comparable action. Furthermore, our model predicts the conditions under which the work of inspiration is expected to increase as a consequence of these displacements. Finally, an important distinction is predicted between abdominal displacements caused by gas or liquid accumulation. Although an abdominal gas displacement tends to decrease the resting lung volume, the weight effect of a liquid displacement tends to increase the resting lung volume by pulling down the diaphragm. PMID- 2600013 TI - Differential control of forearm and calf vascular resistance during one-leg exercise. AB - The purpose of this study was to determine whether blood flow (BF) and vascular resistance (VR) are controlled differently in the nonactive arm and leg during submaximal rhythmic exercise. In eight healthy men we simultaneously measured BF to the forearm and calf (venous occlusion plethysmography) and arterial blood pressure (sphygmomanometry) and calculated whole limb VR before (control) and during 3 min of cycling with the contralateral leg at 38, 56, and 75% of peak one leg O2 uptake (VO2). During the initial phase of exercise (0-1.5 min) at all work loads, BF increased and VR decreased in the forearm (P less than 0.05), whereas calf BF and VR remained at control levels. Thereafter, BF decreased and VR increased in parallel and progressive fashion in both limbs. At end exercise, forearm BF and VR were not different from control values (P greater than 0.05); however, in the calf, BF tended to be lower (P less than 0.05 at 75% peak VO2 only) and VR was higher (23 +/- 9, 44 +/- 14, and 88 +/- 23% above control at 38, 56, and 75% of peak VO2, respectively, all P less than 0.05). In a second series of studies, forearm and calf skin blood flow (laser-Doppler velocimetry) and arterial pressure were measured during the same levels of exercise in six of the subjects. Compared with control, skin BF was unchanged and VR was increased (P less than 0.05) in the forearm by end exercise at all work loads, whereas calf skin BF increased (P less than 0.05) and VR decreased (P less than 0.05). The present findings indicate that skeletal muscle and skin VR are controlled differently in the nonactive forearm and calf during the initial phase of rhythmic exercise with the contralateral leg. Skeletal muscle vasodilation occurs in the forearm but not in the calf; forearm skin vasoconstricts, whereas calf skin vasodilates. Finally, during exercise a time-dependent vasoconstriction occurs in the skeletal muscle of both limbs. PMID- 2600014 TI - Influence of muscle mass on sympathetic neural activation during isometric exercise. AB - The primary purpose of this study was to determine whether the sympathetic neural activation induced by isometric exercise is influenced by the size of the contracting muscle mass. To address this, in nine healthy subjects (aged 19-27 yr) we measured heart rate, systolic arterial blood pressure, and muscle sympathetic nerve activity in the leg (MSNA; peroneal nerve) before (control) and during 2.5 min of isometric handgrip exercise (30% of maximal voluntary force). Exercise was performed with the right and left arms separately and with both arms simultaneously (random order). During exercise, heart rate, systolic pressure, and MSNA increased above control under all conditions (P less than 0.05). For each variable, the magnitudes of the increases from control to the end of exercise were significantly greater when exercise was performed with two arms compared with either arm alone (P less than 0.05). In general, the increases in heart rate, systolic pressure, and MSNA elicited during two-arm exercise were significantly less than the simple sums of the responses evoked during exercise of each arm separately. These findings indicate that the magnitude of the sympathetic neural activation evoked during isometric exercise in humans is determined in part by the size of the active muscle mass. In addition, our results suggest that the sympathetic cardiovascular adjustments elicited during exercise of separate limbs are not simply additive but instead exhibit an inhibitory interaction (i.e., neural occlusion). PMID- 2600015 TI - Work capacity during 30 days of bed rest with isotonic and isokinetic exercise training. AB - The purpose was to test the hypothesis that twice daily, short-term, variable intensity isotonic and intermittent high-intensity isokinetic leg exercise would maintain peak O2 uptake (VO2) and muscular strength and endurance, respectively, at or near ambulatory control levels during 30 days of -6 degrees head-down bed rest (BR) deconditioning. Nineteen men (aged 32-42 yr) were divided into no exercise control (peak VO2 once/wk, n = 5), isokinetic (Lido ergometer, n = 7), and isotonic (Quinton ergometer, n = 7) groups. Exercise training was conducted in the supine position for two 30-min periods/day for 5 days/wk. Isotonic training was at 60-90% of peak VO2, and isokinetic training (knee flexion extension) was at 100 degrees/s. Mean (+/- SE) changes (P less than 0.05) in peak VO2 (ml.m-1.kg-1) from ambulatory control to BR day 28 were 44 +/- 4 to 36 +/- 3, -18.2% (3.27-2.60 l/m) for no exercise, 39 +/- 4 to 40 +/- 3, +2.6% (3.13-3.14 l/min) for isotonic, and 44 +/- 3 to 40 +/- 2, -9.1% (3.24-2.90 l/min) for isokinetic. There were no significant changes in any groups in leg peak torque (right knee flexion or extension), leg mean total work, arm total peak torque, or arm mean total work. Mean energy costs for the isotonic and isokinetic exercise training were 446 kcal/h (18.8 +/- 1.6 ml.min-1.kg-1) and 214 kcal/h (8.9 +/- 0.5 ml.m-1.kg-1), respectively. Thus near-peak, variable intensity, isotonic leg exercise maintains peak VO2 during 30 days of BR, while this peak, intermittent, isokinetic leg exercise protocol does not. PMID- 2600016 TI - Hindlimb suspension suppresses muscle growth and satellite cell proliferation. AB - The effects of long-term hindlimb unweighting by tail suspension on postnatal growth of 20-day rat extensor digitorum longus (EDL) and soleus muscles were studied. Morphological assay indicated that radial growth of soleus myofibers was completely inhibited between 3 and 10 days of suspension and reduced thereafter, leading to a severe attenuation (-76% from control) over the total experimental period. Longitudinal growth rate, however, was accelerated 40% over weight bearing controls. In addition, myofibers were arranged parallel to the long axis of the muscle, an orientation associated with chronologically younger muscles, suggesting morphological maturation of the soleus muscle had been delayed by suspension. In contrast, radial and longitudinal growth of EDL myofibers were minimally affected under similar conditions and remained within approximately 5% of control at all times. Suspension also influenced the normal changes that occur in satellite cell and myonuclear populations during postnatal growth. Both the number and proliferative activity of satellite cells were severely reduced in individual myofibers after only 3 days in both soleus and EDL muscles. The reduced number of satellite cells within 3 days of initiating hindlimb suspension appeared to be the result of their incorporation into myofibers while the long lasting reduction appeared to be the added effects of decreased proliferative activity. In the soleus, this reduction in number and proliferation of satellite cells persisted throughout the experimental period and resulted in an overall 43% fewer myonuclei and 45% fewer satellite cells than control at 50 days of age. In contrast, both the total number and mitotic activity of satellite cells in the EDL rapidly returned to weight-bearing control levels by day 10 of suspension, resulting in no overall reduction in myonuclear accretion. PMID- 2600017 TI - Influence of carbohydrate dosage on exercise performance and glycogen metabolism. AB - This study was undertaken to examine the effects of ingestion of carbohydrate (CHO) solutions of 0 (WP), 6 (CHO-6), 12 (CHO-12), and 18 g CHO/100 ml (CHO-18) on performance and muscle glycogen use. Ten trained cyclists performed five 120 min cycling trials. The first 105 min of each trial was at 70% of maximal O2 consumption (VO2max), and the final 15 min was an all-out performance ride on an isokinetic cycle ergometer equipped to measure total work output. In one of the trials (CHO-12I) the submaximal portion of the ride consisted of seven 15-min rides at 70% of VO2max with a 3-min rest between each ride. Every 15 min the men consumed 8.5 ml.kg-1.h-1 (approximately 150 ml) of one of the four test solutions. Venous blood samples were obtained every 15 min for glucose and insulin. Muscle biopsies were obtained from the vastus lateralis at 0 and 105 min in the WP and the CHO-12 continuous and intermittent trials. Biopsy samples were assayed for glycogen and sectioned and stained for myosin adenosinetriphosphatase and glycogen for single fiber depletion measurements. There were no differences in glycogen use (86.7 +/- 6.0, 75.5 +/- 7.9, and 83.5 +/- 5.5 mmol/kg for the WP, CHO-12C, and CHO-12I, respectively) or depletion patterns between the WP and the two CHO-12 trials. Blood glucose was significantly elevated in both the CHO-12 trials and in the CHO-18 trial compared with the WP trial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600018 TI - Pulmonary transvascular flux of transferrin. AB - We compared the pulmonary transvascular fluxes of transferrin and albumin in the intact sheep lung. Anesthetized sheep were prepared with lung lymph fistulas. The vascular blood pool was marked with 99mTc-erythrocytes, autologous transferrin was labeled with 113mIn, and albumin was labeled with 125I. Samples of blood, plasma, lymph, and lung were obtained up to 180 min after tracer infusion. Lymph tissue radioactivities were corrected for the intravascular component and expressed as extravascular-to-plasma concentration ratios. Clearance of transferrin and albumin from the plasma space followed a two-compartment model. The clearance rate constant was 2.1 +/- 0.1 x 10(-3) min for albumin and 2.4 +/- 0.1 x 10(-3) min for transferrin (P less than 0.05). Lymph-to-plasma ratios for albumin and transferrin were not different. However, the extravascular-to-plasma ratio for albumin was greater than transferrin (P less than 0.05). The lymph and lung data were deconvoluted for the plasma input function and fit to a two compartment model. The results indicate that albumin and transferrin have similar permeabilities across the vascular barrier but have different pulmonary circulation to lymph kinetics because the extravascular volume of distribution of albumin is greater than transferrin. PMID- 2600019 TI - Blood flow distribution in rat muscles during preexercise anticipatory response. AB - Previous work has suggested that preexercise "anticipatory" blood flow distribution in the muscles of rats is influenced by the intensity of the preceding conditioning or training program. The purpose of this study was to carefully control the conditioning programs for control, low-speed conditioned, and high-speed conditioned rats to determine the respective effects on preexercise mean arterial pressure (Pa), heart rate (HR), and blood flow distribution in muscles and other organs. Control (daily placement on treadmill, no exercise), low-speed conditioned (daily treadmill walking up a 12 degree incline at 15 m/min), and high-speed conditioned (daily treadmill galloping up a 12 degree incline at 50 m/min) rats were conditioned for 2-4 wk in their respective programs. On the experimental day, the circulatory variables were measured immediately before exercise by using the same preexercise regimen as during the conditioning sessions. Pa, HR, and blood flow distribution were the same in control and low-speed conditioned rats (P greater than 0.05). However, in high-speed conditioned rats, HR (+9%), Pa (+7%), and white gastrocnemius muscle (+46%) blood flow were higher than in controls (P less than 0.05). The higher white muscle flow was the result of the higher Pa and lower resistance to flow. These data demonstrate that specific changes in preexercise anticipatory blood flow distribution among muscles occur during exercise conditioning programs and that the changes are dependent on the intensity of the conditioning regimen. The mechanisms responsible for the adaptations are not known. PMID- 2600020 TI - Iron deficiency decreases gluconeogenesis in isolated rat hepatocytes. AB - Dietary iron deficiency in rats results in increased blood glucose turnover and recycling. We measured the rates of glucose production in isolated hepatocytes from iron-sufficient (Fe+) and iron-deficient (Fe-) rats to assess the intrinsic capacity of the Fe- liver to carry out gluconeogenesis. Low-iron and control diets were given to 21-day-old female rats. After 4-5 wk, hemoglobin concentrations averaged 4.1 g/dl in the Fe- and 14.3 g/dl in the Fe+ animals. In the hepatocytes from Fe- rats, there was a 35% decrease in the rate of glucose production from 1 mM pyruvate + 10 mM lactate, a 48% decrease from 0.1 mM pyruvate + 1 mM lactate, a 39% decrease from 1 mM alanine, and a 48% decrease from 1 mM glycerol. The addition of 5 microM norepinephrine or 0.5 microM glucagon to the incubation media produced stimulatory effects on hepatocytes from both Fe- and Fe+ rats, resulting in the maintenance of an average difference of 38% in the rates of gluconeogenesis between the two groups. Studies on isolated liver mitochondria and cytosol revealed alpha-glycerophosphate-cytochrome c reductase and phospho(enol)pyruvate carboxykinase activities to be decreased by 27% in Fe- rats. We conclude that because severe dietary iron deficiency decreases gluconeogenesis in isolated rat hepatocytes, the increased gluconeogenesis demonstrated by Fe- rats in vivo is attributable to increased availability of gluconeogenic substrates and upregulation of the pathway. PMID- 2600021 TI - Step response of lung surface-to-volume ratio by light-scattering stereology. AB - By means of backscattered light from a pointlike source on the pleural surface, we investigated the dynamic behavior of the surface-to-volume ratio (S/V) in excised dog lobes subjected to small volume steps both in and out on both the inflation and deflation limb of standard pressure-volume maneuvers. The technique utilizes the established correlation of the pattern of backscattered light with morphometric mean linear intercept and is suitable for dynamic studies. We hypothesized that 1) there would be a difference in the timing of stress relaxation or recovery between alveolar septa and the fibromuscular tissue in the alveolar duct that would reveal itself as a temporally changing S/V after a step volume change and 2) that geometric hysteresis (looping of S/V with volume), as seen with large volume excursion histories, would be similarly present in small tidal volume loops. Our experimental results contradicted both hypotheses. In particular, we found virtually no change in S/V after a step-volume change, even in the presence of substantial stress adaptation. In addition, when geometric hysteresis of small loops was present, it was always in the sense opposite to the geometric hysteresis of large loops. We conclude that 1) there is a functional "matching" of the stress-adaptive timing between alveolar septa and ductal mouths and 2) during small volume looping, the stress hysteresis (looping of stress with volume) in the ductal tissue may be larger than that of the septa, including surface tension. PMID- 2600022 TI - Relative importance of aerobic and anaerobic energy release during short-lasting exhausting bicycle exercise. AB - Anaerobic energy release is of great importance for shortlasting exercise but has been difficult to quantify. In order to determine the amount of anaerobic energy release during shortlasting exercise we let 17 healthy young males exercise on the ergometer bike to exhaustion. The power during exercise was kept constant and selected to cause exhaustion in approximately 30 s, 1 min, or 2-3 min. The O2 uptake was measured continuously during the exercise, and the anaerobic energy release was quantified by the accumulated O2 deficit. The work done as well as the total energy release rose linearly with the exercise duration and was therefore a sum of a component proportional to time plus a constant addition. The accumulated O2 deficit increased from 1.86 +/- 0.07 (SE) mmol/kg for 30 s exercise to 2.25 +/- 0.06 mmol/kg for 1 min exercise and further to 2.42 +/- 0.08 mmol/kg for exercise lasting 2 min or more (P less than 0.01). The accumulated O2 uptake increased linearly with the duration, and as a consequence of this the relative importance of aerobic processes increased from 40% at 30 s duration to 50% at 1 min duration and further to 65% for exercise lasting 2 min. These results show that both aerobic and anaerobic processes contribute significantly during intense exercise lasting from 30 s to 3 min. PMID- 2600023 TI - Protein clearance from the air spaces and lungs of unanesthetized sheep over 144 h. AB - We studied the rate, the routes, and the mechanisms for protein clearance from the air spaces and lungs of 20 unanesthetized sheep over 144 h. We instilled 100 ml of autologous serum labeled with 125I-albumin into one lung. At the end of 24, 48, 96, or 144 h, the lungs were removed and the residual native protein and 125I albumin in the air spaces were determined by bronchoalveolar lavage. Also the fraction of the instilled 125I-albumin remaining in the rest of the lung was measured in the lung homogenate. Clearance of the 125I-albumin from the lung into the plasma, lymph, thyroid, urine, and feces was also determined. The removal of both the 125I-albumin and the native protein from the air spaces was slow, following a monoexponential decline. The removal rate of the 125I-albumin from the air spaces was slightly but significantly faster (1.6%/h) than the clearance rate of the native protein (0.9%/h). Clearance of the 125I-albumin from the lung also followed a slow monoexponential decline at a rate of 1.4%/h. At all time periods, 75% of the 125I-albumin remaining in the lung was located in the air spaces, thus indicating that the pulmonary epithelium is the principal barrier to protein clearance from the normal lung. Macrophages appeared to play a minor role in alveolar protein clearance because the quantity of 125I-albumin present in the phagocytic cells in the air spaces was less than 1% of the instilled 125I-albumin at all time periods. However, macrophages may play some role in protein clearance after 48 h because we visualized phagolysosomes in macrophages, and there was an increase in free iodine in lung lavage, urine, thyroid, and feces after 48 h. However, gel electrophoretic studies showed that most of the 125I-albumin was cleared from the lung as an intact molecule, although only 24.7 +/- 4.7% of the 125I-albumin was cleared by the lymphatics. PMID- 2600024 TI - Fate of air emboli in the pulmonary circulation. AB - The lung serves an important nonrespiratory function by trapping and excreting venous air emboli. The site of trapping and the mechanism of excretion, however, are uncertain. To observe the behavior of bubbles in the pulmonary circulation, we injected venous air emboli into anesthetized dogs and videotaped their elimination from the pulmonary microcirculation by using in vivo microscopy. Small intravenous bubbles lodged exclusively in pulmonary arterioles and were eliminated from that site. To determine whether the gas was dissolving into nearby blood and then was carried to the capillaries for excretion, the rate of bubble radius change was measured during nonperfused conditions produced by balloon occlusion of lobar blood flow and compared with perfused conditions. Bubble volume decreased at the same rate during perfused and nonperfused conditions and thus was independent of regional blood flow. Molecular diffusion of gas directly across the arteriolar wall into alveolar spaces was the most likely mechanism of elimination because calculations based on the Fick equation for molecular diffusion predict an elimination rate nearly identical with those observed experimentally. PMID- 2600025 TI - Field use of D2 18O to measure energy expenditure of soldiers at different energy intakes. AB - To test the application of doubly labeled water under adverse field conditions, energy expenditures of 16 special operations soldiers were measured during a 28 day field training exercise. Subjects were matched by fat-free mass and divided equally between an ad libitum ready-to-eat meal diet and a 2,000 kcal/day lightweight ration. Subjects recorded intakes daily, and body composition was measured before and after the exercise. At the beginning of the study, subjects moved to a new northerly location and, therefore, a new water supply. To compensate for this, a group of soldiers who did not receive heavy water was followed to measure isotopic base-line changes. Energy expenditure by doubly labeled water was in agreement with intake/balance (3,400 +/- 260 vs. 3,230 +/- 520 kcal/day). The overall coefficient of variation of energy expenditure by doubly labeled water was half that of intake/balance (7.6 vs. 16.1%). The coefficient of variation of repeat measures with doubly labeled water was 7.3%. Energy expenditure of the ready-to-eat meal group, 3,540 +/- 180 kcal/day, was not significantly different from the lightweight ration group, 3,330 +/- 301 kcal/day. Doubly labeled water was valid under field conditions. PMID- 2600026 TI - Lengths and topology of alveolar septal borders. AB - To clarify the mechanics of alveolar parenchyma, we undertook a stereological and topological study in perfusion-fixed canine lungs of the borders of alveolar septa. We defined the principal borders as those along which one septum 1) joins two others (J), 2) joins one other at a distinct angle (B), or 3) joins no other structure (E). E and B borders are invariably reinforced with heavy connective tissue cables; J borders are not. Relative net lengths, determined from the number of traces per section area, were J, 45%; E, 19%; and B, 25%. These were remarkably constant over 10 canine lobes (5 animals, 4 volumes). Parenchyma, then, departs from the simple models that comprise only Js and Es. Bs are important; their net length exceeds that of Es. With lobe deflation, E shortened somewhat more than required to maintain geometric similarity, suggesting that the alveolar duct contracted disproportionately. A three-dimensional reconstruction was made from serial sections, and individual border segments were followed through the reconstruction. Typical lengths of individual J, B, and E borders were nearly equal. To characterize how the network of borders were interconnected, we counted the nodes at which they meet by class, e.g., EBE for the meeting of one B, two Es. The most common are JJJJ, 26%; EEEJ, 10%; EBJ, 24%; EBE, 8%; BBJJ, 12%. If parenchyma were constructed only from free-standing entrance rings and septal junctions, only JJJJ and EEEJ would be anticipated. The presence of EBJ, EBE, and BBJJ underscores parenchymal complexity. Only 7% of septa examined were bordered entirely by Js. Connective tissue cables were not confined to the alveolar duct's lumen but often extended to the primary septa at the periphery of the ductal unit. They rarely linked adjacent alveolar ducts; only 1 in 200 cable segments crossed from one duct to another. These observations support the concept that the parenchyma is an elastic network, characterized in part by a serial mechanical linkage from connective tissue cable to septal membrane to cable again. PMID- 2600027 TI - Distribution of elastin and collagen in canine lung alveolar parenchyma. AB - We have quantified the fibrous collagen (predominantly type I) and elastin in four locations of perceived mechanical importance: one quasi-planar feature, the alveolar septum or wall (W), and three linear features, the junction (J) of three septa, the free edges (E) of septa, and the line along which two septa join at a distinct angle or bend (B). The frequencies of these four features on light micrographs and the areas of transections through collagen and elastin seen on electron micrographs were combined to give the volumes of collagen and elastin within each feature. We find that E and B have similar compositions and contain most (4/5) of the parenchymal elastin in their relatively heavy cables. The E and B are interconnected and similar in location and composition, and they may constitute a functional entity in which elastin provides tension over a range of lung volumes, opposing septal tensions. In J and W, elastin is typically sparse and fine. Calculations, however, suggest it contributes the dominant portion of septal tension at lower lung volumes. Elastin may be essential to stabilizing septal configuration. Collagen, on the other hand, is distributed relatively evenly throughout E, B, J, and W, consistent with the role of protecting all components against rupture. PMID- 2600028 TI - Size-related differences in parietal extrapleural and pleural liquid pressure distribution. AB - The hydraulic pressure in the extrapleural parietal interstitium (Pepl) and in the pleural space over the costal side (Pliq) was measured in anesthetized spontaneously breathing supine adult mammals of increasing size (rats, dogs, and sheep) using saline-filled catheters and cannulas, respectively. From the Pliq and Pepl vs. lung height regressions it appears that in all species Pliq was significantly more subatmospheric than Pepl simultaneously measured at the same lung height. The vertical pleural liquid pressure gradient increased with size, amounting to -1, -0.69, and -0.44 cmH2O/cm in rats, dogs, and sheep, respectively. The vertical extrapleural liquid pressure gradient also increased with size, being -0.6, -0.52, and -0.33 cmH2O/cm in rats, dogs, and sheep, respectively. With increasing body size, the transpleural hydraulic pressure gradient (Ptp = Pepl - Pliq) at the level of the right atrium increased from 1.45 to 5.6 cmH2O going from rats to sheep. In all species Ptp increased, with lung height being greatest in the less dependent part of the pleural space. PMID- 2600029 TI - Human respiratory impedance from 8 to 256 Hz corrected for upper airway shunt. AB - Respiratory input impedance (Zrs) was measured from 8 to 256 Hz in 10 healthy subjects by a method that eliminated the shunt impedance of extrathoracic airway walls. It consisted of combining the data obtained with a pressure input at the mouth (standard method, Zst) and with a pressure input around the head (Zhg) Zrs = Zst.(Zp + Zhg)/(Zp + Zst) where Zp is the impedance of the mouthpiece and pneumotachograph. Large quantitative differences were observed between Zrs and Zst, demonstrating that the standard method is unreliable at such frequencies. The real part of Zrs increased from 2.6 +/- 0.8 cmH2O.l-1.s at 8 Hz to a maximum of 38 +/- 19 cmH2O.l-1.s at 158 +/- 49 Hz. The imaginary part exhibited a maximum of 19 +/- 8 cmH2O.l-1.s at 126 +/- 38 Hz, a resonance at 157 +/- 43 Hz, and a minimum of lambda 19 +/- 16 cmH2O.l-1.s at 185 +/- 45 Hz. The data were analyzed with five models featuring alveolar gas compressibility; tissue resistance, inertance, and compliance; and different representations of the airways with lumped and distributed parameters. All except the simplest (lumped frequency dependent resistance) fitted the data equally well, but none provided reliable estimates of gas compliance. Three models gave a consistent description of the airway in terms of equivalent rigid tubes (cross-sectional area 3.5-3.7 cm2, length 47-51 cm). We conclude that high-frequency input impedance could prove useful in exploring the airways but not the peripheral lung. PMID- 2600030 TI - Furosemide reduces lung fluid filtration in lambs with lung microvascular injury from air emboli. AB - To study the effects of furosemide on the neonatal pulmonary circulation in the presence of lung injury, we measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, and concentrations of protein in lymph and plasma of nine lambs that received furosemide, 2 mg/kg iv, during a continuous 8-h intravenous infusion of air. Air embolism increased pulmonary vascular resistance by 71% and nearly tripled steady-state lung lymph flow, with no change in lymph-to-plasma protein ratio. These findings reflect an increase in lung vascular protein permeability. During sustained lung endothelial injury, diuresis from furosemide led to a rapid reduction in cardiac output (average 29%) and a 2-Torr decrease in left atrial pressure. Diuresis also led to hemoconcentration, with a 15% increase in both plasma and lymph protein concentrations. These changes were associated with a 27% reduction in lung lymph flow. In a second set of studies, we prevented the reduction in left atrial pressure after furosemide by inflating a balloon catheter in the left atrium. Nevertheless, lymph flow decreased by 25%, commensurate with the reduction in cardiac output that occurred after furosemide. In a third series of experiments, we minimized the furosemide-related decrease in cardiac output by opening an external fistula between the carotid artery and jugular vein immediately after injection of furosemide. In these studies, the reduction in lung lymph flow (average 17%) paralleled the smaller (17%) decrease in cardiac output. These results suggest that changes in lung vascular filtration pressure probably do not account for the reduction in lung lymph flow after furosemide in the presence of lung vascular injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600031 TI - Afferent and cardiodynamic drives in the early phase of exercise hyperpnea in humans. AB - The ventilatory and cardiac responses to voluntary and passive exercise were studied in 20 healthy subjects. These responses to passive leg exercise were also studied in 23 patients with spinal cord transection at the level of T5-T12. In the normal subjects, minute ventilation (VE) increased abruptly from the first breath after the onset of the two types of exercise. In contrast, cardiac output (Q) increased gradually in voluntary exercise, exhibiting significant augmentation from the fifth breath. Q changed insignificantly in passive exercise. In the patients with spinal cord transection, neither VE nor Q changed with passive exercise. These results suggest that ventilatory responses at the onset of mild exercise are related to drives from the moving limbs. We could not detect any evidence to support cardiodynamic hyperpnea at the onset of exercise. PMID- 2600032 TI - Lung structure parameters estimated from modeling aerosol deposition in isolated dog lungs. AB - A three-compartment model predicting the recovery of aerosol boli (i.e., the ratio of the number of particles expired to the number inspired) as a function of breath-holding time and bolus penetration was fitted to experimental data measured in nine isolated dog lungs. For each lung, the diameters of alveoli and alveolar ducts, as well as the volume fractions of alveoli, alveolar ducts, and airways, were determined as parameters providing the best fit. Parameter values were alveolar diameter = 0.116 +/- 0.007 (SE) mm, alveolar duct diameter = 0.284 +/- 0.015 mm, total alveolar volume/total lung capacity (TLC) = 0.68 +/- 0.02, total alveolar duct volume/TLC = 0.24 +/- 0.02, and total airway volume/TLC = 0.09 +/- 0.01. These values agreed with published values for linear dimensions and volumetric fractions in the canine lung. The mean alveolar diameter determined by the model in the nine lungs agreed closely with a mean value of 0.115 +/- 0.002 mm determined by morphometric analysis of photographs of the subpleural alveoli in the same lungs. The procedure of fitting the model to experimental data appears to have promise as a noninvasive probe of the lung periphery. However, aerosol-derived dimensions were more variable than morphometric ones, possibly because of interlung differences in aerosol distribution not accounted for in the model. PMID- 2600033 TI - Appearance of "transitional" motor units in overloaded rat skeletal muscle. AB - The contractile characteristics of single motor units, isolated from rat plantaris muscles subjected to short-term (30 days) compensatory overload, were assessed to determine whether motor units in transition could be detected. In the control plantaris 88% of the motor units were classified as fast. After overload, a large decline (26.5%) in the proportion of typical fast motor units was noted. The estimated contribution of fast fatigable units to whole muscle tetanic tension (Po 200) also declined (from 55 to 25%), whereas that of fast intermediate motor units increased (from 33 to 55%). In the overloaded plantaris, motor units that exhibited unusual "sag" and contraction time characteristics were detected. These motor units, which could be further subdivided into two distinct types by a variety of indexes, exhibited characteristics intermediate to fast and slow units and therefore were termed "transitional." Transitional units accounted for 12% of the estimated whole muscle Po200 after overload. These experiments characterize novel classifications of motor units undergoing transformation and further detail the motor unit shift that accompanies compensatory overload. PMID- 2600034 TI - Effects of sustained exercise on pulmonary clearance of aerosolized 99mTc-DTPA. AB - The effects of intensive prolonged exercise on the pulmonary clearance rate of aerosolized 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA) and pulmonary mechanics were studied in seven healthy nonsmoking volunteers. 99mTc DTPA clearance and pulmonary mechanics (lung volumes and compliance) were assessed before and after 75 min of constant-load exercise performed on a treadmill, corresponding to 75% of maximal O2 uptake. Because both clearance measurements were made in similar conditions of pulmonary blood flow, respiratory rate, and tidal volume, changes in clearance rate can be assumed to represent changes of alveolar epithelial permeability. After exercise, total, apical, and basal clearance were significantly increased (P less than 0.01, 0.05, and 0.05, respectively) and the increases in total clearance and tidal volume observed during exercise were significantly correlated (P less than 0.05). In contrast, no significant change was found in pulmonary mechanics. These results show that prolonged intensive exercise induces an increase in epithelial permeability, which appears to be related to the mechanical effects of sustained increased ventilation. Because no change was evidenced in pulmonary volumes or in lung elasticity, our results suggest that this increase may result from alteration of the intercellular tight junctions rather than from a surfactant deficiency. PMID- 2600035 TI - Contracture and change in membrane potential produced by sodium removal in the dog trachea and bronchiole. AB - Mechanical responses and changes in membrane potential induced by Na removal were investigated in dog tracheal and bronchiolar smooth muscles. In both muscles, reduction of the external Na concentration ([Na]o) to less than 70 mM produced a sustained contracture, dose dependently. The relative amplitude of the Na-free contracture was greater than that induced by excess [K]o in the trachealis. Readmission of 1-10 mM Na, after exposure to Na-free solution, relaxed the contracture evoked by Na removal, and the degree of relaxation was dependent on [Na] readmitted. In the absence of both Na and Ca, some tension remained, and readmission of Ca increased the muscle tone. Even after pretreatment with Ca-free ethylene glycol-bis (beta-aminoethylether)-N,N,N,N'-tetraacetic acid- (0.2 mM) containing solution for 30 min, removal of Na caused some mechanical response in both muscles. D 600 (10(-7) to 10(-4) M), a blocker of voltage-dependent Ca2+ influx, suppressed the response to Na removal, but 10(-4) M D 600 did not completely block the contracture. Na removal depolarized the smooth muscle membrane to a greater extent in the bronchiole than in the trachealis. It was concluded that an increase in Ca permeability across the membrane and inhibition of the Na-Ca exchange mechanism in the absence of Na are responsible for the generation of Na-free contracture in both muscles. PMID- 2600037 TI - Changes of time constants during infancy and early childhood. AB - We used respiratory inductance plethysmography to record tidal respiration in 27 healthy unsedated infants and children 1 mo to 8 yr of age during sleep. Rib cage and abdominal outputs were present at approximately equal gains and summed to obtain an estimate of volume. Flow-volume curves were generated from the uncalibrated volume signal and its flow derivative. Expiratory time constants (tau) were obtained by visually drawing a line through the linear portion of the expiratory flow-volume relationship. tau increased significantly during the first 10 mo of life. After 10 mo, the estimated rate of increase of tau for older children was less than 5% of the estimated initial rate and not significantly different from zero. Prolongation of tau was paralleled by an increase in expiratory time (Te), and no changes in Te/tau were observed in the first 2 yr of life. These changes in tau likely reflect the increase in lung compliance induced by rapid alveolar growth during infancy. After the first year, expiratory time constants appear to remain relatively constant and may be consistent with balanced changes in compliance and resistance beyond infancy. PMID- 2600036 TI - Transition from dynamically maintained to relaxed end-expiratory volume in human infants. AB - Newborn infants, in contrast to adults, dynamically maintain end-expiratory lung volume (EEV) above relaxation volume. The purpose of this study was to determine at what age children develop a breathing strategy that is relaxed, i.e., determined by the mechanical characteristics of the lung and chest wall. Forty studies were performed in 27 healthy infants and children aged 1 mo to 8 yr during natural sleep. Volume changes were recorded with the use of respiratory inductance plethysmography (RIP). The volume signal was differentiated to yield flow. Flow-volume representations were generated for a random sample of the recorded breaths to determine the predominant breathing strategy utilized, i.e., relaxed, interrupted, or indeterminate. The respiratory pattern was predominantly interrupted below 6 mo of age and predominantly relaxed over 1 yr of age. Mixed patterns were observed in children 6-12 mo of age. The number of breaths that could not be classified (indeterminate) decreased with age. Respiratory frequency measured from the sample of breaths decreased with age and was accompanied by an increase in expiratory time. We conclude that a relaxed EEV develops at the end of the first year of life and may be related to changes in the mechanical properties of the chest wall associated with growth as well as changes in respiratory timing. PMID- 2600038 TI - Species dependence of baroreceptor effects on ventilation in the cat and the dog. AB - Reflex respiratory responses to brief carotid baroreceptor stimuli in vagotomized pentobarbital-anesthetized cats were characterized and compared with those reported previously for chloralose-anesthetized dogs. To eliminate effects due to the anesthetic choice, dogs were reexamined under pentobarbital. Stimuli were applied to the isolated carotid sinus (CS) of both animals within a single respiratory phase. The stimuli were either steps triggered after one of four delays (5, 25, 50, and 75% of the control phase duration) and terminated at the end of the phase or pulses lasting 300-500 ms. In cats, 80-mmHg steps during inspiration shortened inspiratory duration by 23.2*, 25.0*, 20.4*, and 4.1% (*P less than 0.01) at the above four delays, respectively; inspired volume decreased by 21.4*, 18.0*, 8.0*, and 2.2%. Steps during expiration lengthened expiration by 38.4*, 37.1*, 21.9*, and 3.4%; expired volume changed less than 4%. Qualitatively, similar responses were obtained with steps 40 mmHg in amplitude. In dogs, 40-mmHg stimuli lengthened both inspiration (by 12.8*, 8.9*, -1.2, and 2.5%) and expiration (by 75.2*, 57.9*, 54.0*, and 61.4*%) but tidal volume did not change. Similar differences were observed when pulses were used. Selective baroreceptor denervation in the cat and occipital arterial occlusion in the dog confirmed that the responses were not chemoreceptor mediated. We conclude that although CS baroreceptor activity inhibits ventilation in both cats and dogs, the pattern of the responses is strongly species dependent. PMID- 2600039 TI - Electrode for selective recording of electromyograms from intercostal muscles. AB - An electromyogram-recording electrode is described that makes it possible to record separately the electrical signals generated within two closely approximated muscle layers. The device consists of two bipolar wire hook electrodes embedded in opposite faces of a thin laminated plastic wafer. The middle lamina of the wafer is a sheet of metal foil that shields the electrical field on one side of the wafer from the bipolar electrode on the other side. The device was tested by inserting it from the inside of the chest wall between the internal and external intercostal muscle layers. Signals from the two muscle layers were clearly separated. Single motor unit spikes were attenuated by factors ranging from 41 to 2.4. The device can be implanted with minimal trauma to surrounding muscles and is suitable for chronic animal experiments. PMID- 2600040 TI - Validation of oxygen consumption measurements during artificial ventilation. AB - We describe a system for the absolute calibration of indirect calorimeters, under the conditions of artificial ventilation and increased inspired O2 concentration, in which butane, at a measured flow rate, is burned downstream of an artificial lung. One milliliter of butane requires 6.4 ml O2 for its combustion, and the respiratory quotient is 0.615. With the closed-circuit O2-replenishment method there was no significant systematic error in the measurement of either O2 consumption or CO2 output and a random error with a SD of 8.3 ml/min for O2 consumption and 6.3 ml/min for CO2 output. There were no significant differences in the errors with inspired O2 concentrations between 23.8 and 59.5% and O2 consumptions between 89 and 366 ml/min. PMID- 2600042 TI - In situ isolated perfused and innervated left hemidiaphragm preparation. AB - We developed a vascularly isolated in situ preparation of the left hemidiaphragm in which arterial blood was only provided through the left phrenic artery and the venous blood only drained through the phrenic vein. The costal margins were secured and connected to three force transducers. Muscle shortening was measured by sonomicrometry. The presence of arterial collaterals between the left hemidiaphragm and the systemic circulation was excluded by the systemic injection of a vital dye (Lissamine Green), a neuromuscular blocking agent (succinylcholine), and by the injection of epinephrine. Left phrenic nerve stimulation produced homogeneous shortening and tension. The degree of shortening in the isolated and intact left diaphragm at the same resting length was similar. The preparation was stable for 2 h with less than 10% decline in maximum tension. Two advantages of this preparation are particularly important. 1) Diaphragmatic energetics can be studied independently of systemic factors, and 2) the role of phrenic nerve afferents in the control of breathing and systemic circulation can easily be assessed without activating nonphrenic nerve afferents. PMID- 2600043 TI - Responses of isolated guinea pig pulmonary venules to hypoxia and anoxia. AB - Because small pulmonary arteries are believed to be the major site of hypoxic pulmonary vasoconstriction (HPV), pulmonary venular responses to hypoxia have received little attention. Therefore the responses of isolated guinea pig pulmonary venules to hypoxia (bath PO2, 25 Torr) and anoxia (bath PO2, 0 Torr) were characterized. Pulmonary venules [effective lumen radius (ELR), 116 +/- 2 microns] with an adherent layer of parenchyma responded to hypoxia and anoxia with a graded sustained contraction (hypoxia, 0.03 +/- 0.01; anoxia, 0.26 +/- 0.03 mN/mm), whereas paired femoral venules (ELR, 184 +/- 7 microns) contracted to anoxia only (0.05 +/- 0.02 mN/mm). Repeated challenges with hypoxia and anoxia continued to elicit sustained pulmonary venular contractions; femoral venule contractions to anoxia were not repeatable. Hypoxia- and anoxia-induced pulmonary venular contractions were calcium and pH dependent. Dissection of the parenchyma from pulmonary venules did not alter contractions to decreased PO2. Anoxic contractions of pulmonary venules were variably reduced by replacement of the bath fluid; however, the release of a contractile mediator(s) from pulmonary venules during hypoxia or anoxia was not demonstrated. Pulmonary venular responses to hypoxia and anoxia are similar to those induced by hypoxia in vivo, and results obtained from this model may be useful in predicting mechanisms of HPV. PMID- 2600041 TI - Operation Everest II: comparison of four instruments for measuring blood O2 saturation. AB - The bias and precision of four different methods for determining O2 saturation (SO2) were evaluated during a study of hypobaric hypoxia conducted with seven male subjects exposed progressively over a 40-day period to simulated altitudes from sea level (760 Torr) to 8,840 m (240 Torr). SO2 of arterial and mixed venous blood samples were measured with the Instrumentation Laboratory 282 CO-oximeter (CO-OX), the Radiometer ABL-300 (ABL), and the Lex-O2-Con-K (LEX). Noninvasive measurements of arterial SO2 were made with a Hewlett-Packard 47201A ear oximeter (EAR-OX). The CO-OX method was used as a secondary standard for comparison with the other methods because it has been validated against the classical Van Slyke method over a wide physiological range (Maas et al., Clin. Chim. Acta 29: 303 309, 1970). The LEX results most closely approximated but consistently underestimated those of the CO-OX: LEX = 0.93 CO-OX -0.86, standard error of the estimate (SEE) = 5.17, r = 0.98, n = 670. The ABL method appeared to combine two linear trends: for SO2 greater than 75%, ABL = 0.84 CO-OX +14.4, SEE = 1.77, r = 0.97, n = 369; less than 75%, ABL = 0.98 CO-OX +5.9, SEE = 4.44, r = 0.97, n = 486. The EAR-OX results were found to approximate those of the CO-OX at SO2 values only greater than 65%: EAR-OX = 1.07 CO-OX -6.12, SEE = 7.71, r = 0.98, n = 326.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600044 TI - Changes in body temperature of rats acclimated to heat with different acclimation schedules. AB - Male Wistar rats, initially maintained at an ambient temperature (Ta) of 23.8 degrees C, were subjected to one of seven different heat acclimation schedules under a 12:12-h light-dark cycle (lights on at 0600 h). Two groups of rats were exposed to Ta of 32.4 degrees C all day for 5 (HC5) or 10 (HC10) days. The other four groups were exposed to Ta of 32.8 degrees C for 5 h/day during the last half of the dark phase for 5 (NI5) or 10 (NI10) consecutive days or during the last half of the light phase for 5 (DI5) or 10 (DI10) consecutive days. Control rats (C) were kept at 23.8 degrees C throughout the experiment. Hypothalamic temperature (Thy) was measured every 5 min with a chronically implanted thermocouple from 1 day before the beginning to 2 days after the end of the heat acclimation periods. During the heat acclimation periods, daily mean Thy rose significantly in HC5 and HC10 rats but decreased significantly in NI5 and NI10 rats. Daily mean Thy did not change in C, DI5, and DI10 rats. Thy in HC10 rats sharply decreased at the end of the heat acclimation periods and remained at low levels for approximately 3 h. On the 2nd postacclimation day, however, mean Thy returned and remained at a significantly higher level. In NI10 rats, the mean Thy in the postacclimation period was significantly lower than the preacclimation values. No such changes in mean Thy were observed in DI10 rats. Five-days of heat exposure had little effect on the postacclimation Thy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600045 TI - Hemoglobin O2 affinity and tissue hypoxia. PMID- 2600046 TI - Chronic occupational stressors, self-focused attention, and well-being: testing a cybernetic model of stress. AB - By using a cybernetic approach to occupational stress, it was hypothesized that the relationship between chronic work stressors and strain would be stronger among individuals high in private self-consciousness than among individuals low in private self-consciousness. Moderated regression analyses, using a sample of 135 blue-collar workers, revealed strong support for this hypothesis. This finding is antithetical to prior research showing that self-focused attention may buffer the effect of acute life events (Mullen & Suls, 1982; Suls & Fletcher, 1985). The results of the present study in conjunction with prior research suggest that the type of stressor (acute vs. chronic) examined may be a boundary condition influencing the direction of Stressor X Self-Focused Attention interactions. Implications for future research and stress management are discussed. PMID- 2600047 TI - Kirlian Photography--A Tool in the Diagnosing of Psychopathology. PMID- 2600048 TI - Axial lighting for in situ photography of heart valves. PMID- 2600050 TI - An interview with Warren Sturgis. Interview by C. Allen Shaffer. PMID- 2600049 TI - A portable fluorescent lighting system for location photography. PMID- 2600051 TI - [Doppler echography: what can one expect from radiology? Report from the symposium of the ultrasonics section of the SRBR-KBVR (Royal Belgian Radiology Society)]. PMID- 2600052 TI - Synovial cyst of the lumbar spine. A case report. AB - Intraspinal ganglions or synovial cysts most frequently involve the L4-L5 level and the adjacent facet joint reveals characteristic alterations of osteo arthritis. These cysts usually present with pain, but without additional sensory or motor findings. They cannot be diagnosed on the basis of conventional radiology; myelography shows a filling defect adjacent to the affected facet joint, and the differential diagnosis includes several common and uncommon entities. The CT appearance is however strongly characteristic, showing a cystic structure with occasionally a calcification within its wall. There often is compression of the adjacent dural sac or nerve roots. PMID- 2600054 TI - Some points of interest in the management of rectal cancer. AB - The author presents the surgeon's viewpoint in the management of rectal cancer outlining the possible contribution of early detection, precise pre-operative evaluation of the tumour extension and the necessity to provide a form of curative and radical treatment while given the best possible quality of life. PMID- 2600053 TI - Cortical hyperostosis: a complication of prostaglandin E1 treatment in congenital heart disease. AB - Prostaglandin E1 (PGE1) is an essential drug for infants with ductal-dependent congenital heart disease. Cortical hyperostosis of the long bones is one of the complications during and after PGE1 therapy and should be considered in the differential diagnosis of periostitis in the infant. PMID- 2600055 TI - Adjuvant radiotherapy to surgery for rectal cancers. AB - A plea is made in favor of adjuvant treatment in rectal cancer by discussing the possible benefit of pre- and post-operative radiotherapy. Intra-operative radiotherapy is described as well as the possible benefit of this new form of treatment. PMID- 2600056 TI - Adjuvant chemotherapy of rectal cancer. AB - The basic principles as well as the possible indications for adjuvant chemotherapy are discussed. An overview of the studies testing chemotherapy alone or combined with radiation or immunotherapy is presented. PMID- 2600057 TI - Tumor markers in colorectal cancer. AB - The value of several tumor markers (CEA, CA 19.9, TPA...) in the diagnosis, prognosis and treatment monitoring of rectal cancer is discussed outlining that CEA remains the best isolated marker. PMID- 2600058 TI - The laser and the lower gastrointestinal tract. AB - The authors review and describe the technique of laser in the management of lower gastrointestinal tract tumors. PMID- 2600059 TI - Rectal cancer: a summary. AB - The authors summarize the most important conclusions of a multicentric multidisciplinary review on rectal cancer in Belgium. PMID- 2600060 TI - Kodak working to advance. PMID- 2600061 TI - Fluoxetine added to non-MAOI antidepressants converts nonresponders to responders: a preliminary report. AB - Thirty depressed outpatients poorly responsive to various non-MAOI antidepressants had fluoxetine added to their regimens. Retrospective analysis revealed that 26 (86.7%) of the patients improved. Non-MAOI antidepressant treatment was withdrawn for 12 of the 26 responders; of these, 8 relapsed on fluoxetine treatment alone but recovered when treatment with the discontinued non MAOI agent was restarted. PMID- 2600062 TI - Normal and disordered compulsivity: evidence against a continuum. AB - Sixteen patients with obsessive compulsive disorder and 16 mentally healthy control subjects of comparable gender, age, and educational level underwent psychometric testing with the Obsessive-Compulsive subscale of the Comprehensive Psychiatric Rating Scale, the Maudsley Obsessive-Compulsive Inventory, and the Obsessive subscale of the Lazare-Klerman-Armor (LKA) Personality Inventory. An interviewer also rated each subject as positive or negative for each of the five DSM-III elements of compulsive personality disorder. Patients scored significantly higher than controls on all measures except the Obsessive subscale of the LKA Personality Inventory, on which the controls actually scored slightly higher. The authors suggest that the failure of this last instrument to differentiate the subject groups can be interpreted as evidence against a continuum between a certain type of supposed normal personality pattern (obsessive or compulsive) and a corresponding psychopathologic state (obsessive compulsive disorder). PMID- 2600063 TI - Zinc deficiency and eating disorders. AB - Decreased food intake, a cyclic pattern of eating, and weight loss are major manifestations of zinc deficiency. In this study, zinc status was evaluated in 62 patients with bulimia and 24 patients with anorexia nervosa. Forty percent of patients with bulimia and 54% of those with anorexia nervosa had biochemical evidence of zinc deficiency. The authors suggest that for a variety of reasons, such as lower dietary intake of zinc, impaired zinc absorption, vomiting, diarrhea, and binging on low-zinc foods, patients with eating disorders may develop zinc deficiency. This acquired zinc deficiency could then add to the chronicity of altered eating behavior in those patients. PMID- 2600064 TI - Childhood sexual abuse in women with bulimia. AB - In a study of the family environments and psychiatric histories of 35 bulimic women, the authors found that 12 (34.3%) of the 35 women had been sexually abused or had a sister who had been sexually abused. That rate is comparable to estimates from other studies of women with eating disorders and of female psychiatric patients, but is apparently higher than the rate found in the general population. Bulimic women from families in which sexual abuse occurred were more likely than bulimic women with no personal or family history of sexual abuse to have a personal history of major depression, relatives who abused drugs, and a disturbed family environment. The presence of bulimia should alert clinicians to screen for concomitant depression, suicidality, and substance abuse as well as the possibility of severe, if hidden, familial pathology and environmental disruption including sexual abuse, parental psychopathology, and character deficits. PMID- 2600065 TI - Non-erotic self-choking in five psychiatric inpatients. AB - Recurrent self-choking without suicidal intent has received limited attention in the literature; most reports have focused on the sexual nature of the behavior. The authors describe five psychiatric inpatients who engaged in repeated non erotic self-choking. Similarities in clinical features of the cases include a history of substance abuse (including abuse of volatile substances), aggressive behaviors, a chronic history of psychotic symptoms leading to repeated long-term hospitalizations, and a sense of relief or pleasure, but no overt sexual stimulation, caused by self-choking. The possible role of limbic system dysfunction in this behavior is considered. PMID- 2600066 TI - Seasonal affective disorder and visual impairment: two case studies. AB - Winter depressive episodes in patients with seasonal affective disorder are induced by light deficiency and are successfully treated by enhancing environmental light. The authors investigated the role of abnormal visual information processing in the genesis of seasonal affective disorder symptoms by examining two patients with impaired vision and recurrent winter depressions. The first patient developed winter depressions after developing a traumatic cataract in one eye, and was helped by light therapy. The second patient, fully blind since she was 1 year old, nonetheless suffered as an adult from winter depressions, which responded to bright--but not to dim--light treatment. The authors discuss the implications of these findings. PMID- 2600067 TI - Delusions in Marfan syndrome. PMID- 2600069 TI - Separation anxiety and fear or avoidance of flying. PMID- 2600068 TI - Lithium and propranolol: possible synergism? PMID- 2600070 TI - Capgras syndrome and minor head trauma. PMID- 2600071 TI - SPECT scan reveals abnormality in somatization disorder patient. PMID- 2600072 TI - Dimenhydrinate addiction in a schizophrenic woman. PMID- 2600073 TI - Mania: important new findings. Proceedings of an educational symposium. May 7, 1989, San Francisco. PMID- 2600074 TI - Cartoons vs. realistic illustration: picture preferences of adolescent patients. AB - Illustrations are an important element in patient education materials because they engage the interest of the audience. However, little research has been conducted to determine the style of illustration that most effectively engages a patient population. This study tested the picture preferences of 39 adolescents with phenylketonuria (PKU). A survey instrument asked them to choose between cartoons and realistic illustrations. A significant number preferred realistic illustrations to cartoons. PMID- 2600075 TI - Caricature: some considerations. AB - Familiarity with caricature illustration will help the medical illustrator look forward to these occasional projects. Tips and the author's experiences are related to help the first-time caricaturist. PMID- 2600076 TI - Vaccinia virus encodes an essential gene with strong homology to protein kinases. AB - The B1 gene of vaccinia virus encodes a 34-kDa protein which is essential for viral replication. Temperature-sensitive mutants bearing lesions in this gene arrest at the stage of DNA replication during nonpermissive infections. In this report, the sequence of the 34-kDa open reading frame is presented, and the mutations in two ts alleles are identified. Analysis of the deduced protein sequence reveals strong homology with catalytic domains of numerous protein kinases. The lesion in one of the mutants alters an invariant glycine residue within one such domain. PMID- 2600077 TI - DNA polymerase gamma from Xenopus laevis. I. The identification of a high molecular weight catalytic subunit by a novel DNA polymerase photolabeling procedure. AB - DNA polymerase gamma has been purified over 10,000-fold from mitochondria of Xenopus laevis ovaries. We have developed a novel technique which specifically photolabels DNA polymerases. This procedure, the DNA polymerase trap, was used to identify a catalytic subunit of 140,000 Da from X. laevis DNA polymerase gamma. Additional catalytically active polypeptides of 100,000 and 55,000 Da were identified in the highly purified enzyme. These appear to be products of degradation of the 140,000-Da subunit. The DNA polymerase trap, which does not require large amounts of enzyme or renaturation from sodium dodecyl sulfate, is an alternative to the classic "activity gel." PMID- 2600078 TI - DNA polymerase gamma from Xenopus laevis. II. A 3'----5' exonuclease is tightly associated with the DNA polymerase activity. AB - Xenopus laevis DNA polymerase gamma co-purifies with a tightly associated 3'--- 5' exonuclease. The purified enzyme lacks 5'----3' exonuclease and endonuclease activity. The ratio of the 3'----5' exonuclease activity to DNA polymerase gamma activity remains constant over the final three chromatographic procedures. In addition, these activities co-sediment under partially denaturing conditions in the presence of ethylene glycol. The associated 3'----5' exonuclease activity removes a terminally mismatched nucleotide more rapidly than a correctly base paired 3'-terminal residue, as expected if this exonuclease has a proofreading function. The 3'----5' exonuclease has the ability to release a terminal phosphorothioated nucleotide, a property shared with T4 DNA polymerase, but not with Escherichia coli DNA polymerase I. PMID- 2600079 TI - Inactivation of monoamine oxidase by 3,3-dimethyl analogues of 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine and 1-methyl-4-phenyl-2,3-dihydropyridinium ion. Dramatic effect of beta-mercaptoethanol on substrate turnover and enzyme inactivation. AB - It was previously shown (Sayre, L. M., Arora, P. K., Feke, S. C., and Urbach, F. L. (1986) J. Am. Chem. Soc. 108, 2464-2466) that 1,3,3-trimethyl-4-phenyl-2,3 dihydropyridinium salt (the 3,3-dimethyl analogue of 1-methyl-4-phenyl-2,3 dihydropyridinium ion or MPDP+) is a good model for MPDP+ on the basis of its redox potential and was used to show that MPDP+ is unlikely to possess reactivity characteristics which could contribute to the neurotoxicity observed with 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 3,3-Dimethyl-MPTP and 3,3 dimethyl-MPDP+ are now shown to interact with monoamine oxidase similar to MPTP and MPDP+, but only in the presence of beta-mercaptoethanol (beta-ME). In the absence of beta-ME, mixed competitive-noncompetitive inhibition kinetics are observed for 3,3-dimethyl-MPTP and 3,3-dimethyl-MPDP+, whereas competitive inhibition kinetics are exhibited by MPTP. In the presence of beta-ME, however, 3,3-dimethyl-MPTP also is a competitive inhibitor. 3,3-Dimethyl-MPTP and 3,3 dimethyl-MPDP+ also are time-dependent inactivators of monoamine oxidase, having identical kinetic constants, as is the case with MPTP and MPDP+. In the presence of beta-ME, but not glutathione, the rate of inactivation increases dramatically. When [beta-ME] and [3,3-dimethyl-MPTP] or [3,3-dimethyl-MPDP+] are varied, there is an optimal concentration of 1.0 mM for all three at which maximal inactivation rates are obtained. Another dramatic effect of the beta-ME is to lower the partition ratio for inactivation from greater than 50 to about one. This suggests that the effect of the beta-ME toward inactivation may be to induce a conformational change in the enzyme, which reorients an active site nucleophile for attack on the activated species. Support for involvement of an active site nucleophile is the finding that inactivation does not lead to a flavin adduct. Three possible mechanisms for inactivation of monoamine oxidase by MPTP and MPDP+ are suggested. PMID- 2600080 TI - Molecular cloning of the high affinity calcium-binding protein (calreticulin) of skeletal muscle sarcoplasmic reticulum. AB - A cDNA clone encoding the high affinity Ca2+-binding protein (HACBP) of rabbit skeletal muscle sarcoplasmic reticulum was isolated and sequenced. The cDNA encoded a protein of 418 amino acids, but a comparison of the deduced amino acid sequence with the NH2-terminal amino acid sequence of the purified protein indicates that a 17-residue NH2-terminal signal sequence was removed during synthesis. This was confirmed by studies of in vitro translation of mRNA encoding the protein. Structural predictions did not reveal any potential transmembrane segments in the protein. The COOH-terminal sequence of the high affinity Ca2+ binding protein, Lys-Asp-Glu-Leu, is the same as that proposed to be an endoplasmic reticulum retention signal (Munro, S., and Pelham, H. R. B. (1987) Cell 48, 899-907). All of these characteristics suggest that the protein is localized in the lumen of the sarcoplasmic reticulum. The mature protein of Mr 46,567 contains 109 acidic and 52 basic amino acids. Structural predictions suggest that the first half of the molecule forms a globular domain of 8 anti parallel beta-strands with a helix-turn-helix motif at the extreme NH2 terminus. The next one-third of the sequence is proline-rich. This segment can be subdivided into a charged region which contains a 17-amino acid repeat, followed by a proline, serine, and threonine-rich segment extending from Pro-246 to Thr 316. Thirty-seven acidic residues are clustered within 56 amino acids at the COOH terminus of the protein. Although the protein binds 1 mol of Ca2+/mol with high affinity, no "EF-hand" consensus sequence was observed in the protein. The acidic COOH terminus, however, could account for the low affinity, high capacity Ca2+ binding observed in the protein. In agreement with other involved laboratories, we have chosen the name calreticulin for the protein. PMID- 2600081 TI - Activation of glucose transport in skeletal muscle by phospholipase C and phorbol ester. Evaluation of the regulatory roles of protein kinase C and calcium. AB - It has been hypothesized on the basis of studies on BC3H-1 myocytes that diacylglycerol generation with activation of protein kinase C (PKC) is involved in the stimulation of glucose transport in muscle by insulin (Standaert, M. L., Farese, R. V., Cooper, R. D., and Pollet, R. J. (1988) J. Biol. Chem. 263, 8696 8705). In the present study, we used the rat epitrochlearis muscle to evaluate the possibility that PKC activity mediates the stimulation of glucose transport by insulin in mammalian skeletal muscle. Phospholipase C from Clostridium perfringens (PLC-Cp), which generates diacylglycerol from membrane phospholipids, and 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) induced increases in glucose transport activity (assessed using 3-O-methylglucose transport) that were approximately 80 and approximately 20% as great, respectively, as that induced by a maximal insulin stimulus. PLC-Cp and PMA both caused a approximately 2-fold increase in membrane-associated PKC activity. In contrast, insulin did not affect PKC activity. These findings argue against a role of diacylglycerol-mediated PKC activation in the stimulation of skeletal muscle glucose transport by insulin. They also show that the BC3H-1 myocyte is not a good model for studying regulation of glucose transport in skeletal muscle. Neither the submaximal nor maximal effects of PLC-Cp and insulin on glucose transport were additive, suggesting that PLC-Cp interferes with insulin action. The maximal effects of PLC Cp and hypoxia or muscle contractions were also not additive. However, the submaximal effects of hypoxia and PLC-Cp were completely additive. These findings raise the possibility that PLC-Cp stimulates glucose transport by the exercise/hypoxia-activated, not the insulin-activated, pathway in skeletal muscle. Exposure to PLC-Cp activated glycogen phosphorylase and potentiated twitch tension in response to electrical stimulation, providing evidence that PLC Cp increases cytoplasmic Ca2+ concentration. Dantrolene, an inhibitor of Ca2+ release from the sarcoplasmic reticulum, completely blocked both the activation of phosphorylase and the stimulation of glucose transport by PLC-Cp. These findings provide evidence that an increase in cytoplasmic Ca2+ concentration is involved in the activation of glucose transport in skeletal muscle by PLC-Cp. PMID- 2600082 TI - Characterization and platelet inhibitory activity of bitistatin, a potent arginine-glycine-aspartic acid-containing peptide from the venom of the viper Bitis arietans. AB - A platelet aggregation inhibitory protein, bitistatin, was isolated from the venom of the puff adder Bitis arietans. This protein is a single-chain peptide containing 83 amino acids and 7 disulfide bonds. Bitistatin contains the sequence arginine-glycine-aspartic acid and shows considerable homology to two previously described snake venom platelet aggregation inhibitors, trigramin and echistatin. Bitistatin inhibited human and canine platelet aggregation initiated by 10 microM ADP in vitro with IC50 values of 237 +/- 13 and 28 +/- 3 nM, respectively. In order to assess the antithrombotic potential of bitistatin, a canine model of platelet-dependent coronary thrombus formation was utilized. Injection of bitistatin at 10-100 micrograms/kg (0.7-7 nmol/kg, intravenously (i.v.] resulted in dose-dependent inhibition of both platelet aggregation ex vivo and platelet dependent cyclical flow reductions. The effective dose to inhibit cyclical flow reductions was 30 micrograms/kg, i.v. A higher dose of bitistatin (100 micrograms/kg, i.v.) inhibited cyclical flow reductions for 160 +/- 29 min as well as attenuated ex vivo platelet aggregation. Bitistatin at 100 micrograms/kg, i.v. prolonged the bleeding time 4 x normal at 15 min post-administration but returned to normal at 3 h. Thus, in a canine model of in vivo platelet aggregation, bitistatin is an effective antiplatelet agent to inhibit periodic cyclical flow reductions. Bitistatin also exhibits reversible effects of ex vivo platelet aggregation as well as on bleeding time. PMID- 2600083 TI - Tissue-specific expression, developmental regulation, and chromosomal mapping of the lecithin: cholesterol acyltransferase gene. Evidence for expression in brain and testes as well as liver. AB - Lecithin:cholesterol acyltransferase (LCAT) catalyzes the esterification of cholesterol in high density lipoproteins, thereby facilitating transport of excess cholesterol from peripheral tissues to liver. We report here studies of the developmental, dietary, and genetic control of LCAT gene expression. In adult male Sprague-Dawley rats fed a standard chow diet LCAT mRNA was most abundant in liver, a major source of the plasma enzyme, but appreciable levels were also present in brain and testes. Since both brain and testes are isolated from blood by tight cellular barriers, undoubtedly greatly reducing the level of plasma derived LCAT in cerebrospinal fluid and testes, the production of LCAT in these tissues may be important for removal of excess cholesterol. Noteworthy changes in the expression of LCAT mRNA were observed during development of both rodents and humans. On the other hand, LCAT mRNA levels were relatively resistant to dietary challenge or to drugs affecting cholesterol metabolism. Since human epidemiological studies have suggested an association between LCAT levels and variations of high density lipoprotein cholesterol, we examined LCAT gene polymorphisms in a mouse animal model. Mapping of the LCAT gene (Lcat) to mouse Chromosome 8 within 2 centimorgans of the Es-2 locus indicates that it does not correspond to any previously mapped loci affecting high density lipoprotein phenotypes in the mouse. PMID- 2600084 TI - A novel metalloproteinase associated with brain myelin membranes. Isolation and characterization. AB - Brain myelin membrane preparations contain a metalloproteinase activity which degrades myelin basic protein (MBP). The activity was associated with lentil lectin-binding glycoproteins solubilized from myelin and could be detected in the presence of the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS). The metalloproteinase represented about 5% of this glycoprotein fraction and was isolated from it by chromatography on DEAE Sephacel, CM-Sepharose, and Superose 6. The proteinase had an apparent relative molecular weight (Mr) of approximately 58,000 both by gel filtration and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The Mr value was unaffected by the presence of reducing agents but was diminished to about 52,000 by treating the proteinase with endoglycosidase F. The purified proteinase cleaved many bonds in MBP but did not generate trichloroacetic acid-soluble products. Two major polypeptides, putatively MBP1-73 and MBP74-170, were prominent in digests of MBP by either the purified enzyme or myelin membranes. The proteinase was active between pH 7 and 9 and was inhibited by phenanthroline and dithiothreitol but not phosphoramidon or inhibitors of serine or cysteine proteinases. Histones, but not azocasein, also served as substrates for the proteinase. From its enzymic and molecular characteristics the myelin-derived metalloproteinase appears distinct from previously described enzymes. PMID- 2600085 TI - Two forms of omega-hydroxylase toward prostaglandin A and laurate. cDNA cloning and their expression. AB - We have isolated cDNA clones for two forms of P-450s, P-450ka-1 and P-450ka-2, from a rabbit kidney cDNA library, using the cDNA for rabbit pulmonary cytochrome P-450p-2, a prostaglandin omega-hydroxylase (Matsubara, S., Yamamoto, S., Sogawa, K., Yokotani, N., Fujii-Kuriyama, Y., Haniu, M., Shively, J.E., Gotoh, O., Kusunose, E., and Kusunose, M. (1987) J. Biol. Chem. 262, 13366-13371), as a hybridization probe. The cDNAs for P-450ka-1 and P-450ka-2 encode polypeptides of 510 and 511 amino acids, respectively, with sequence similarity of 85% and 87% to P-450p-2. The two deduced primary structures have 87% identity. RNA blot analysis demonstrated that the mRNAs for P-450ka-1 and P-450ka-2 formed single bands at approximately 3.0- and 2.6-kilobase positions, respectively. The mRNA for P-450ka 1 was expressed only in the liver and kidney and was increased remarkably in these tissues by the administration of clofibrate. In contrast, the mRNA for P 450ka-2 was expressed constitutively in the liver, kidney, and small intestine, but its transcription was enhanced only in the liver by clofibrate treatment. Thus, in spite of their high sequence similarity, these P-450 species have different modes of regulatory expression. Comparison of the nucleotide sequences among P-450ka-1, P-450ka-2, and P-450p-2 shows about 90% overall sequence similarity in any pair of the three sequences. Nucleotide replacements are not evenly distributed, but are rather biased. There is a region of approximately 500 base pairs of exceptionally high homology among the three sequences. These results indicate that the gene conversion event occurred during the evolutionary process of these genes. PMID- 2600086 TI - Purification and structural identification of an autoinducer for the luminescence system of Vibrio harveyi. AB - An autoinducer required for the growth-dependent development of luminescence in Vibrio harveyi has been purified, structurally identified, and chemically synthesized. The autoinducer, which is excreted by the cells, was extracted with chloroform from conditioned media in which V. harveyi cells had been grown. The concentrated extract was separated on a silica gel column and the autoinducer activity further purified by thin layer, paper, and high performance liquid chromatography. The structure of the partially purified autoinducer was identified by 1H NMR and mass spectrometry as N-(beta-hydroxybutyryl)homoserine lactone. This compound was chemically synthesized by condensation of beta hydroxybutyrate with alpha-amino-gamma-butyrolactone hydrobromide using 1-ethyl-3 (3-dimethylaminopropyl)carbodiimide as a carboxyl group activator. The pure synthetic autoinducer gave the characteristic NMR and mass spectra, co-migrated with the natural autoinducer on thin layer plates, and specifically stimulated induction of luminescence of V. harveyi. Light emission of a regulatory dark mutant of V. harveyi could be stimulated over 1000-fold by the addition of N (beta-hydroxybutyryl)homoserine lactone, reaching intensities comparable to that of the native strain. The similarity in structure of the autoinducer of V. harveyi to that of Vibrio fischeri suggests that the regulation of luminescence induction in these bacteria may be related in spite of their differences in lux gene organization. PMID- 2600087 TI - Different combinations of cysteine-rich repeats mediate binding of low density lipoprotein receptor to two different proteins. AB - Seven imperfect repeats of a 40-amino acid cysteine-rich sequence constitute the ligand binding domain of the low density lipoprotein (LDL) receptor. To assess the contribution of each repeat, three site-directed mutations were made individually in each repeat: 1) deletion of the repeat, 2) substitution of a conserved isoleucine with aspartic acid, and 3) substitution of a conserved aspartic acid with tyrosine. cDNAs containing these mutations were transfected into simian COS cells and assayed for their ability to bind LDL, which contains a 500-kDa protein ligand (apoB-100), and beta-migrating very low density lipoprotein (beta-VLDL), which contains multiple copies of a 33-kDa ligand (apoE). The results showed that binding of the two ligands required different combinations of repeats. LDL binding required repeats 3-7; deletion of any one of these repeats markedly reduced LDL binding. In contrast, beta-migrating very low density lipoprotein binding was insensitive to the loss of any single repeat with the important exception of repeat 5, whose loss reduced binding by 60%. The same effects were obtained when each of the repeats was altered by either of the two substitution mutations. The current findings suggest that a multiplicity of cysteine-rich repeats may allow a single protein to bind several different protein ligands by employing different combinations of repeats. PMID- 2600088 TI - Platelet-activating factor enhances complement-dependent phagocytosis of diamide treated erythrocytes by human monocytes through activation of protein kinase C and phosphorylation of complement receptor type one (CR1). AB - Oligomerization of band 3 protein has been recently indicated as an early event in senescent or damaged red cell membrane followed by specific deposition of anti band 3 antibodies and binding of complement C3 fragments. The band 3-anti-band 3 C3b complex is recognized by homologous monocytes, and phagocytosis ensues. This study shows that recognition of the anti-band 3-C3b complex by the monocyte C3b receptor type one (CR1) plays a crucial role in the process of removal of damaged red cells. Indeed, blocking of monocyte CR1 with an anti-CR1 monoclonal antibody abrogated phagocytosis of diamide-treated red cells. Platelet-activating factor (PAF) is a phospholipid mediator involved in inflammatory processes. Nanomolar (R)-PAF enhanced the CR1-dependent phagocytosis of diamide-treated human red cell and of sheep red cells coated with C3b, induced the fast translocation of protein kinase C to monocyte membrane compartment, and stimulated the phosphorylation of monocyte CR1. The biologically inert lyso-PAF and the enantiomer (S)-PAF were inactive. PAF receptor antagonists and inhibitors of protein kinase C blocked the enhancement of phagocytosis induced by PAF. Protein kinase C translocation, phosphorylation of CR1, and stimulation of this receptor to an active state capable of mediating phagocytosis represent a novel pathway by which PAF interferes with red cell homeostasis and possibly modulates inflammatory reactions and host mechanisms against infections. PMID- 2600089 TI - Transforming growth factor-beta switches the pattern of integrins expressed in MG 63 human osteosarcoma cells and causes a selective loss of cell adhesion to laminin. AB - Transforming growth factor-beta (TGF-beta) induces a marked decrease in adhesion of MG-63 human osteosarcoma cells to laminin-coated surfaces, but does not significantly alter adhesion to fibronectin- or collagen-coated surfaces. We provide evidence that this effect is due to a switch in the repertoire of cell adhesion receptors in response to TGF-beta. MG-63 cells express high levels of alpha 3 beta 1-integrin, which is a polyspecific laminin/collagen/fibronectin receptor, and low levels of alpha 2 beta 1- and alpha 5 beta 1-integrins, which are collagen and fibronectin receptors, respectively. No other integrins of the beta 1-class could be detected in MG-63 cells. Treatment with TGF-beta 1 induces a marked (approximately 60%) decrease in the level of expression of alpha 3 integrin subunit mRNA and protein and a concomitant 8-fold increase in alpha 2 subunit expression. These responses become maximal 7-12 h after addition of TGF beta 1 to the cells. Expression of alpha 5- and beta 1-integrin subunits also increases in response to TGF-beta 1, but to a lesser extent than alpha 2-subunit expression. Thus, as a result of TGF-beta action, the alpha 2 beta 1-collagen and alpha 5 beta 1-fibronectin receptors replace the alpha 3 beta 1 laminin/collagen/fibronectin receptor as the predominant integrins of the beta 1 class in MG-63 cells. These results suggest that one of the effects of TGF-beta is to modify the adhesive behavior of certain tumor cells by changing the binding specificity of the complement of integrins that they express. PMID- 2600090 TI - Regulation of expression of the CD11b and CD18 subunits of the neutrophil adherence receptor during human myeloid differentiation. AB - The receptor on human myeloid cells that mediates cellular adherence consists of a heterodimer complex (designated CD11b/CD18). This receptor complex plays a critical role in leukocyte chemotaxis, adherence to vascular endothelium, and phagocytosis. We investigated expression of the CD11b subunit of this adherence receptor complex in various leukocyte populations. As previously described for the CD18 subunit, enhanced CD11b surface antigen and mRNA expression are present in peripheral blood granulocytes, as well as in chemically induced, differentiating HL-60 cells. However, in contrast to CD18 mRNA expression, which is transcriptionally regulated in differentiating HL-60 cells, the steady state levels of CD11b mRNA appear to be post-transcriptionally regulated in these cells. Thus, although the steady state levels of mRNA for the individual subunits of the CD11b/CD18 adherence receptor complex generally parallel each other during human myeloid differentiation, the mechanisms responsible for regulating these levels are distinctly different. PMID- 2600091 TI - Purification and molecular characterization of FAP, a feto-acinar protein associated with the differentiation of human pancreas. AB - This work describes the purification of FAP, a feto-acinar pancreatic protein associated with the ontogenesis, differentiation, and transformation of the human exocrine pancreas. The protein was purified to homogeneity from pancreatic juices of patients with pancreatic pathology by a two-step chromatographic procedure which consisted of size exclusion on Sephacryl S-200 and affinity on heparin Sepharose. The final preparation gave a single band at Mr 110,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after Coomassie stain or autoradiography of the 125I-labeled protein. Immunodetection with the murine monoclonal antibody mAb J28 in nitrocellulose replicas demonstrated a main Mr 110,000 component and trace components in the Mr 100,000-80,000 range. The immunopattern was identical to that in the original crude pancreatic secretion, therefore showing that the molecular characteristics of the protein, i.e. molecular mass, microheterogeneity, and immunoreactivity, were not altered along the purification procedure. FAP was identified as an acidic protein (isoelectric point 4.2-4.8) consisting of a single polypeptide chain having no free SH residues. Analysis of the amino acid composition showed a high proline content. Twenty-two residues of the N-terminal sequence were determined. No significant homology between this peptide and other proteins was found following a search of the NBRF-18 data bank. Sugar analysis showed the presence of mannose which is consistent with N-linked carbohydrate chains and an unusual high ratio in N acetylgalactosamine residues suggesting the presence of many O-linked carbohydrate chains. Sequential deglycosylation with neuraminidase, hexosaminidase, and O-glycanase yield a single Mr 58,000 peptide showing that, relative to a molecular mass of 110,000, the carbohydrate moiety of FAP accounts for at least 47% of its apparent Mr by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. PMID- 2600092 TI - Regulation of eukaryotic initiation factor-2B activity by polyamines and amino acid starvation in rabbit reticulocyte lysate. AB - We recently reported that the translational control of protein synthesis by glucose 6-phosphate in gel-filtered, rabbit reticulocyte lysate is exerted on the activity of eukaryotic initiation factor (eIF)-2B, the factor that catalyzes the exchange of GTP for GDP bound to eIF-2, by a mechanism that is independent of the phosphorylation of eIF-2 (alpha subunit). We now demonstrate that two other conditions regulate the activity of eIF-2B in rabbit reticulocyte lysate: polyamines (spermidine and spermine) and amino acid deficiency. In the absence of added polyamines, protein synthesis in gel-filtered lysate is reduced to about 70% and eIF-2B activity to about 35% of optimal. The former is likely a result of the latter, since we find that reticulocyte lysate has about twice the eIF-2B necessary to recycle the eIF-2.GDP generated under conditions of optimal protein synthesis. In contrast, the reduction in eIF-2B activity (to about 50% of optimal) occurring in the absence of added amino acids in unfractionated or gel filtered lysate is insufficient, by itself, to slow the rate of protein synthesis, and the inhibition of protein synthesis that does occur with amino acid deficiency is exerted on polypeptide chain elongation, not initiation. The reduction in eIF-2B activity occurring with amino acid deficiency cannot be reversed by adding more glucose 6-phosphate or polyamines nor can the reduced eIF 2B activity seen with polyamine deficiency be overcome by increasing the glucose 6-phosphate, suggesting that these three components regulate eIF-2B activity by different mechanisms. PMID- 2600093 TI - Interleukin-3 and bryostatin 1 mediate rapid nuclear envelope protein phosphorylation in growth factor-dependent FDC-P1 hematopoietic cells. A possible role for nuclear protein kinase C. AB - Interleukin-3 (IL-3) is a lymphokine which stimulates the proliferation of normal and transformed multilineage hematopoietic cells. Recently we reported that bryostatin 1, a macrocyclic lactone and potent activator of protein kinase C, could stimulate normal multipotential hematopoietic progenitor cells in vitro in the absence of added polypeptide growth factors. We have now used the murine IL-3 dependent cell line FDC-P1, derived from normal murine marrow cells, to examine the early biochemical events associated with stimulation of hematopoietic cells. We find that both IL-3 and bryostatin 1 are mitogenic and stimulate the growth of FDC-P1 cells. Cells grown for extended periods in the presence of bryostatin 1 (1 nM) alone retain IL-3 responsiveness, indicating that bryostatin 1 does not induce an IL-3-independent state. Protein phosphorylation studies in cells treated with either IL-3 or bryostatin 1 indicate that both stimulators can mediate the rapid (within 5 min) serine-specific phosphorylation of several nuclear envelope polypeptides, including lamin B. Both IL-3- and bryostatin 1 mediated nuclear envelope phosphorylation is dose-dependent, occurring at concentrations which are mitogenic to FDC-P1 cells. The extent of nuclear envelope phosphorylation mediated by IL-3 and bryostatin 1 correlates with the mitogenic response. Furthermore, both mitogens mediate the rapid immunologic translocation of protein kinase C to the nuclear envelope where phosphorylation occurs. These data indicate that the early mitogenic signal(s) generated by IL-3 and bryostatin 1 may converge at the level of the nuclear envelope, perhaps through a protein kinase C-like activity which mediates phosphorylation of specific nuclear envelope polypeptides such as lamin B. PMID- 2600094 TI - Techniques to accelerate the availability of human keratinocyte grafts. AB - Human keratinocytes grown in cultures have been used successfully in the coverage of large burns. The time required to grow sufficient human keratinocytes for grafting is a major limitation of this technique. Three variables--plating density, length of time to confluence in secondary culture, and media supplementation--were studied to find conditions that increase the rate of keratinocyte growth. Normal human keratinocytes were used for all studies. Plating densities varied between 2.5 x 10(3) and 3.7 x 10(4) cells per square centimeter. Time in secondary culture was studied daily from day 2 to day 17. Media supplements included fetal bovine serum, human serum, and three commercially available serum supplements. These studies indicate that human keratinocytes, grown for wound grafting, can grow more rapidly to a higher cell number if they are plated at a density of 2 x 10(4) cells per square centimeter, passaged by 8 to 10 days or before confluence slows cell growth, and grown in 5% fetal bovine serum, 1.25% fetal bovine serum, or 5% human serum. Use of these techniques may decrease the time necessary for wound coverage with human keratinocytes. PMID- 2600095 TI - Healing characteristics of expanded autografts on wounds covered with homograft and Biobrane temporary wound dressing. AB - This study compared the healing characteristics of expanded autografts on wounds with interstices that were closed with cryopreserved cadaver homograft split thickness skin and wounds with interstices that were closed with the synthetic skin substitute, Biobrane temporary wound dressing. Nine paired wounds in four patients with large burns were used in this study. When Biobrane temporary wound dressing adhered to a wound, epithelial migration did not proceed until it was removed. Although wounds covered with homograft immediately had the appearance of healed wounds, biopsy specimens showed evidence of a delay in epithelial migration. Although these results indicate impaired epithelial migration with the use of both materials, we concluded that homograft offered an advantage because the wounds that were covered with it remained closed during the entire reepithelialization process. PMID- 2600096 TI - Alteration in temperature regulation induced by burn injury in the rat. AB - The preoptic anterior hypothalamus (POAH) of rats housed at three ambient temperatures was implanted with perfusion apparatuses. Response of heat production to displacement of POAH temperature was determined for control animals and animals with burns (31% +/- 3% total body surface area). At an ambient temperature of 22 degrees C there was a significant increase in thermosensitivity of the POAH for both control rats and rats with burns compared with thermosensitivity at 32 degrees C. Within ambient temperatures there was no effect on thermosensitivity detected for rats with burns compared with control rats. The threshold temperature for heat production was shifted significantly upward (p less than 0.05) both by a lower ambient temperature and by burn injury. The reference temperature for heat production was also shifted to the right by burn injury (p less than 0.05). The significant shifts to the right for threshold temperature and reference temperature for heat production enhance the organisms's ability to meet the stress of the hypermetabolic response. At a warm ambient temperature (32 degrees C) there are no significant differences in thermoregulation detected in animals with burns or control animals. PMID- 2600097 TI - Application of autologous fibrin glue in burn wounds. AB - Biological adhesive fixation of skin grafts has been performed successfully on patients with facial burns and burns at difficult sites by using autologous human fibrin adhesive, which eliminates the danger of multidonor pool preparations. There are several distinct advantages to the use of fibrin glue: There is no danger of multidonor pool preparations. Wounds do not require any sutures or pressure dressings in the immediate postoperative period. Grafts demonstrate excellent take with minimal postoperative care. The patients can maintain normal ambulation. Fibrin glue seems to be an important factor in the application of skin grafts to burned areas in these two groups of patients. PMID- 2600098 TI - The efficacy of nystatin combined with topical microbial agents in the treatment of burn wound sepsis. AB - Pilot in vitro studies demonstrated that nystatin combined with Silvadene (silver sulfadiazine 1% [Marion Laboratories, Inc., Kansas City Mo.]) or Furacin in a 1:1 ratio was equally effective against Candida albicans and ATCC strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, but Sulfamylon (Winthrop Pharmaceuticals, Winthrop, N.Y.) combined with nystatin demonstrated an antagonistic response. Therefore we examined the susceptibility to nystatin of 165 clinical isolates, both gram-positive and gram-negative, to nystatin combined with Silvadene or Sulfamylon and 144 isolates to nystatin and Furacin. Both Silvadene and Furacin combined with nystatin were equally effective against the microorganisms as were the individual drugs. Conversely, Sulfamylon combined with nystatin lost its antimicrobial capability (93.3% resistance, p less than 0.001). On the basis of the in vitro results, 93 patients with acute burns were treated with the appropriate topical antimicrobials from April 1988 to September 1988. Of the 93 patients treated, 90 had neither a major systemic bacterial nor a Candida sepsis, and none of these patients had associated localized burn wound sepsis during their hospital stays. These 90 patients were discharged without any documented signs of infection. The average burnsize was greater than or equal to 29.44% total body surface area. These data suggest that the antimicrobial properties of nystatin, when combined with Silvadene and Furacin, remain effective. Consequently, such combinations have been effective in controlling both local and systemic Candida and bacterial burn wound sepsis. PMID- 2600099 TI - Burns and associated nonthermal trauma: an analysis of management, outcome, and relation to the Injury Severity Score. AB - Nonthermal trauma in patients with burns necessitates additional considerations in management. The charts of all patients with nonthermal trauma admitted to a regional burn center from 1977 to 1987 were reviewed. The causative events and types of injury were determined. The most common injuries were fractures caused by jumping from burning buildings. Fracture management varied, and the only complications that occurred among the 15 of 61 patients with fractures were associated with overlying burns. The mortality rate was 20%, which is comparable to that predicted from the patients' ages and the percent of total body surface area burned. The mortality rate predicted from the Injury Severity Score is much lower, which brings into question its use for analysis of this patient population. PMID- 2600100 TI - Caloric needs of adolescent patients with burns. AB - Formulas for estimating the caloric requirements of pediatric and adult patients with burns have been suggested. However, the needs of adolescent patients with burns have not been specifically addressed. This study was undertaken to determine the calorie intake required to maintain weight of adolescent patients with burns over more than 35% of the total body surface area. The 29 patients studied were divided into two groups according to sex. Caloric requirements were determined with the use of the Galveston surface area formula and the Curreri formula. The comparison of these estimations with the actual intake required to maintain weight indicated that there is a significant difference between the calories indicated by the formulas and the actual intake. A surface area formula that also correlates with the results of indirect-calorimetry studies is suggested for this adolescent population with burns. PMID- 2600101 TI - Effect of aggressive surgical treatment in older patients with burns. AB - A group of 103 patients with burns, 65 years old and older, was compared with a similar group treated a decade ago. The survival rate of the early group was 37%, and the survival rate of the currently treated group is 52%. The length of stay in the hospital of surviving patients dropped from 42 to 22 days. Ten years ago 62% of surviving patients with burns in our series were operated on. In the more recently treated group with improved survival and decreased lengths of stay, 90% of the patients had one or more operations. We believe that early excision of eschar and early wound closure are associated with increased survival and decreased length of stay for older patients with burns. PMID- 2600102 TI - Determinants of donor site infections in small burn grafts. AB - Studies indicate no advantage to the early use of systemic antibiotics in patients with burns, but the use of prophylactic antibiotics during excision is still being questioned. The records of 213 patients who required excision and who had less than 20% total body surface area burned were reviewed. We investigated risk factors associated with donor- and graft-site infections and whether or not perioperative antibiotics influenced the incidence of infections. Statistically significant increases in donor-site infections occurred when patients did not receive perioperative antibiotics, when the excision was large, and when the time between injury and excision was prolonged. Age, burn size, or type of dressing did not influence the development of infections. A risk of graft infections in those patients who were not receiving perioperative antibiotics existed, but it was not significant. The time between injury and excision and the actual size of the excision influence the development of donor-site infections. However, perioperative antibiotics seem to decrease the risk of these infections. PMID- 2600103 TI - Sensory loss over grafted areas in patients with burns. AB - We studied loss of cutaneous sensibility after grafting in 60 patients with burns who had applied for impairment assessment. Fifty-eight patients (97%) demonstrated markedly diminished or absent responses to sharp/dull, hot/cold, and light touch stimuli over grafted areas. However, all but one patient had intact perception over donor areas and over areas of healed (ungrafted) partial thickness burns. Deep touch sensation was intact over both grafted and ungrafted areas in all patients. Loss of sensation was not related to patient age, burn size, or type of burn; nor did sensory loss correlate with the impairment rating received. Depth of burn injury appears to be the best predictor of altered sensation, and some abnormalities in patients appear inevitable after skin grafting. Patients should be counseled about possible outcomes. However, the decrease in sensation that was observed rarely contributed significantly to the long-term impairment rating of these burn victims. PMID- 2600104 TI - Range of motion of the shoulder performed while patient is anesthetized. AB - Significant loss of shoulder range of motion (ROM) in the early stages of burn recovery is a common and frustrating complication of burn injury. Pain is a primary reason for decreased motion: it prevents the patient from cooperating in an aggressive therapy program that could minimize contracture formation. To combat loss of movement without inflicting severe pain, the performance of ROM exercises and gentle passive stretching while patients were anesthetized was used as a treatment. A total of 59 treatments were performed on 14 patients who had limited unilateral or bilateral shoulder motion. A significant gain in shoulder ROM was attained when this treatment was performed and resulted in an increase in shoulder ROM when the patient was alert after anesthesia compared with preanesthesia measurements. PMID- 2600105 TI - Serial casting: a method for treating burn contractures. AB - The purpose of this study was to assess the effectiveness of serial casting of burn contractures that were resistant to traditional methods of treatment such as paraffin therapy, massage, exercise, and splinting. Serial casting was used to increase the range of motion in 35 joints in 15 patients with burns. A mean increase of 54% was achieved. Casting provided immediate results with minimal complications and was accepted well by patients. Casts were easy to apply and effective even with noncompliant patients. They also delayed or eliminated the need for surgical correction. PMID- 2600106 TI - Microcomputer image processing for burn patients. AB - A computer-based system was developed to handle information and images in a clinical setting. The system is based on an 80286 AT computer, the topology of which includes a 16-bit color image capture/display graphics adapter and a 256 gray scale 8-bit digital image analysis processor. Using its color capabilities, we have created a picture database of patients' injuries, radiographs, and other relevant clinical data. The computer-based imaging system allows instant access to this information and minimizes subjective evaluation, making comparison of and follow-up of treatments more objective. The image analysis components permit digital characterization of the burn wound, enhancing our ability to quantitatively evaluate wound size, contracture, graft take, and re epithelialization. This is a cost-effective method of handling information and images in the clinical setting as well as an effective research and teaching tool that facilitates management and follow-up care of the patient with burns. PMID- 2600107 TI - Adaptation of self-image in burn-disfigured children. AB - Massive burn injury alters both the physical appearance and the functional ability of the child. The changed body necessitates concomitant alteration of the internal self-image, including feelings about the internal self or self-esteem. Six children of primary school age are being followed up in a prospective, longitudinal study to track their adaptation to burn disfigurement. Results of the first 5 1/2 years reveal that, initially, all children displayed pervasive developmental regression, accompanied by phobias, nightmares, and various other symptoms. Two years later, one half of the children had returned to the average range of development attainment. By the fifth year, five of the six children had returned to an average level of progressive personality development. The sixth child was progressing well considering cognitive and emotional deficits before the burn injury. A primary factor influencing adaptation appeared to be the role of the parent or parents in facilitating the acquisition of a positive self-image and in launching and maintaining active mastery in their children. PMID- 2600108 TI - Inventory of potential reconstructive needs in the patient with burns. AB - The rehabilitation and reconstruction of patients who survive large burns is an arduous task. To facilitate it we have devised an inventory form to accurately record the somatic abnormalities caused by burns and also the severity and location of burns. This form was used in the assessment of 25 pediatric patients with massive burns. It was found to be a very useful tool that allowed the identification of more specific functional and esthetic deformities than is possible with currently available forms. It also served as a template for the systematic planning of reconstructive procedures. PMID- 2600109 TI - Developing a regional and national burn disaster response. AB - The supplement on burns by the National Disaster Medical System (NDMS) requires an evaluation of burn centers' and burn hospitals' capabilities for treating seriously burned victims. The American Burn Association (ABA) and its members, as experts in burn care, should take the lead in working with local, state, and federal disaster planners. Proposals based on standards adopted by the ABA support classification of facilities (levels I, II, III), identify minimum and maximum bed availability, require minimum training for personnel (e.g., ABLS), and encourage enrollment of all burn centers and burn hospitals as contract hospitals in the National Disaster Medical System. Periodically, the ABA should verify that the burn care facilities identified in the disaster plan meet its standards. Once the burn disaster system is developed, drills should be held locally on a regular basis and nationally on an annual basis. PMID- 2600110 TI - Infection control in the burn unit. PMID- 2600111 TI - The entrapped retrosternal drainage catheter. Nonoperative removal. AB - Although rare in occurrence, entrapment of mediastinal drainage catheter by sternal wires following median sternotomy can be frustrating. Described is a simple nonoperative technique for removal. PMID- 2600112 TI - Nonocclusive intestinal ischemia and necrosis after correction of interatrial communication with cardiopulmonary bypass. A rare and catastrophic complication. AB - The authors present a case of massive, nonocclusive intestinal ischemia and necrosis after surgery for correction of interatrial communication with cardiopulmonary bypass in a 22-year-old woman. This is an extremely serious complication that generally occurs in older patients. The literature mentions its occurrence in patients subjected to aortic valve replacement who have low cardiac output and in patients undergoing myocardial revascularization. Its occurrence in a young person with simple congenital cardiopathy is rare. PMID- 2600113 TI - Surgical treatment for myocardial bridge using intraoperative echocardiography. A report of two cases. AB - Two cases of symptomatic myocardial bridging of the left anterior descending coronary artery (LAD) requiring surgery for relief of exertional angina are reported. High-frequency intraoperative echocardiography was used for imaging of the intramyocardial coronary artery lesions before and after supraarterial myotomy performed under cardiopulmonary bypass. The constricting band of the myocardial bridge could be clearly demonstrated. Supraarterial myotomy was successfully carried out in each patient. We conclude that intraoperative echocardiography for detecting myocardial bridge is a useful tool for supraarterial myotomy. PMID- 2600114 TI - Transient radial nerve injury related to the use of a self retaining retractor for internal mammary artery dissection. AB - Peripheral nerve injuries and brachial plexopathies are frequent complications for coronary artery surgery, and are related to median sternotomy. Radial nerve injury has been uncommon hitherto. We report the case of a patient who sustained a radial nerve palsy associated with the use of a Pittman retractor, but who achieved rapid and complete recovery. PMID- 2600115 TI - Airway compromise after carotid surgery in patients with cervical irradiation. AB - Symptomatic carotid atherosclerotic disease occurring as a result of cervical irradiation often requires surgical intervention. Airway obstruction is an uncommon problem after most carotid surgery and has not been described for patients with cervical irradiation. Airway obstruction developed after two of five carotid endarterectomy procedures in previously irradiated necks requiring emergency tracheostomy or reintubation. Mechanisms of obstruction included endotracheal tube trauma to the fixed irradiated vocal cords and laryngeal edema caused by surgical dissection in an irradiated field. In addition, one patient in our series demonstrated hypercarbia as a result of bilateral carotid body ablation, a process known to impair the ventilatory response to hypoxia. An increased risk of airway obstruction after carotid surgery exists in patients with prior cervical irradiation. Preventive methods include the use of perioperative steroids and either carotid surgery with local anesthesia or bronchoscopic vocal cord visualization and intubation. PMID- 2600116 TI - Too few, too late. Temporal artery biopsy in cranial arteritis. AB - A retrospective study of 66 patients with cranial arteritis diagnosed clinically was undertaken, investigating the incidence, timing and adequacy of temporal artery biopsy. Only 36 patients underwent biopsy, of which 24 were positive, 8 negative and 4 surgically inadequate. Only 13 of 24 biopsy positive patients had clinical arterial abnormalities; 5 of 8 biopsy negative patients had clinical abnormalities. Three biopsy positive patients had an ESR of less than 40 mm/hr. The average delay from onset of symptoms to biopsy was 128 days; excluding 3 patients with a delay greater than 6 months, the average delay was 52 days. The average time to diagnosis in the "no biopsy" group from the onset of symptoms was 60 days (excluding 1 patient with a delay greater than 6 months). Serious complications occurred in 15 patients. Of 36 patients undergoing biopsy, 4 had complications (prior to biopsy), whilst of the 30 "no biopsy" patients 11 suffered a serious complication (significant chi 2 = 4,716 with Yates correction, p less than 0.05). The study suggests that diagnosis is delayed in all groups. Earlier biopsies in more patients with meticulous technique would probably speed the diagnosis of cranial arteritis and reduce the incidence of preventable complications. PMID- 2600117 TI - Coarctation of the aorta, early and late results of various surgical techniques. AB - In the 10-year period 1973-1983, 158 patients aged one day to 16.4 years were operated upon for coarctation of the aorta; 25% of them were less than one month of age. The main surgical procedure was aortoplasty with a prosthetic patch (114 patients), and resection and end-to-end anastomosis (36 patients). Associated cardiovascular anomalies were found in 42%. There were 11 early and 6 late deaths and the majority of these were due to severe coexistent cardiac lesions. The frequency of moderate and severe recoarctation was much higher in patients operated on with resection and end-to-end anastomosis than in those with aortoplasty and prosthetic patch, 25% and 6.7%, respectively. In 18 patients, surgery for recoarctation was necessary using aortoplasty and a prosthetic patch technique. There were no postoperative complications or deaths in these patients. So far, in 2 cases with a prosthetic patch, aneurysmal dilatation of the aorta adjacent to the patch has developed. PMID- 2600119 TI - Predicting postoperative arterial pressure in renovascular hypertensive patients. AB - The authors have developed a method for forecasting the degree of the hypotensive effect of surgery for renovascular hypertension. Fifteen digital parameters were determined in 36 patients with unilateral lesions of the renal arteries by the following methods of preoperative examination: the establishment of the duration of hypertension, radio-isotope renography, determination of renin activity in the peripheral and renovascular (venous) blood, rheonephrography. The obtained set of characteristics was used for the prediction of postoperative arterial pressure values by means of one of the methods of mathematical statistics, the regression analysis in an "SM-4" electronic computer according to a specially created multivariate regression program in the "Fortran-4" language. The high accuracy of predicting the arterial pressure by this method was confirmed by clinical trials. Forecasting postoperative arterial pressure by this method allows us to substantiate with a high degree of fidelity the advisability of reconstructive surgery and opens up realistic prospects for improving its results. PMID- 2600118 TI - Results of 132 PTFE (Gore-Tex) bifurcated graft implantations. AB - One hundred and thirty-two PTFE bifurcated prosthetic grafts were implanted during the course of a bicentre study conducted at the abovenamed institutions from 1982 to 1986. The study included 118 males and 14 females with an average age of 62 years. One hundred and eighteen patients suffered from aorto-iliac occlusive disease and 14 from abdominal aortic aneurysms (AAA). Five patients had already undergone previous surgery (redo operations), with extirpation of thrombosed Dacron prostheses. Proximal end to end anastomoses were fashioned in 94 cases (71.2%), while end to side anastomoses were performed in 38 cases (28.8%). The distal anastomoses were to the iliac arteries in 11 cases, the common femoral artery in 89 cases and the deep femoral artery in 32 cases. PMID- 2600120 TI - Implantation technique and complications of totally implanted arterial access systems for long-term therapy in patients with occlusive vascular disease. AB - Twenty-six totally implantable catheter systems for intra-arterial infusions were used in patients with peripheral arterial occlusive disease. A total of 606 short term infusions were administered via the system. The patients were observed up to 22 months. There was an over-all rate of complications in 15.3%. The complications described were: one catheter occlusion, one dislocation, one case of local infection and one case of arterial thrombosis. The latter was successfully treated with local lysis therapy. The system is distinguished from conventional methods of arterial access by its long-term use and the low incidence of complications. The system was extremely well accepted by the patients. PMID- 2600121 TI - Acute ischemia-reperfusion injury in the canine hindlimb. AB - A canine arterial ligation preparation was used to produce whole limb ischemia reperfusion injury. Alterations in the distribution of arterial blood flow as well as the morphology of skeletal muscle ischemia-reperfusion have not been investigated completely in this setting. Five anesthetized adult mongrel dogs underwent multiple infrarenal aortic branch ligations; one randomly selected hindlimb was subjected to six hours of ischemia and two hours of reperfusion, while the opposite limb served as control. Distribution of arterial blood flow was analyzed by injection of radiolabeled microspheres. Electromagnetically measured femoral arterial blood flow was 92 +/- 10 ml/min during control, and increased significantly (p less than 0.05) to 254 +/- 94 ml/min during reperfusion. Flow distribution to skin, muscle, and bone was 9 +/- 2%, 68 +/- 7%, and 8 +/- 1% during control, and 7 +/- 3%, 65 +/- 8%, and 9 +/- 4% after reperfusion, which did not represent significant changes. Arteriovenous shunting was 11 +/- 4% during control, and was 13 +/- 5% during reperfusion, which was not significantly different. Subcellular injury in the ischemic and reperfused hindlimb was demonstrated by light and electron microscopy. These findings further characterize whole limb ischemia-reperfusion injury in the canine hindlimb. PMID- 2600122 TI - Correlation of long-term results of femoropopliteal autogenous vein grafts with shear stress variation. In situ or reversed graft? AB - To investigate the correlation between blood flow rate and shear stress variation (tau-variation), the integral of time differential of wall shear stress in one cardiac cycle and the outcome of the vein graft, 42 consecutive patients with femoropopliteal autovein grafts (24 in situ and 18 reversed grafts) were followed for 3 months to 5 years after surgical repair. No correlation was noted between the intraoperative blood flow rate and the outcome of the vein grafts with either procedure. In contrast, the tau-variation value of the vein grafts was closely related to their outcome with both procedures. The higher the tau-variation, the better the long-term results. Vein grafts with a tau-variation of over 60 dyn/cm2 showed good long-term results. The in situ grafts tended to have a higher tau variation than the reversed grafts (67% in the in situ grafts vs 39% in the reversed grafts). Late failures were noted in vein grafts with low tau-variation value within 3 years after surgery. We recommend the in situ graft technique for patients undergoing femoropopliteal reconstruction, with careful follow-up in cases of vein grafts with a low tau-variation value. PMID- 2600123 TI - Aspirin improves the patency rate of seeded vena cava grafts. AB - The purpose of this study was to evaluate the effectiveness of aspirin (ASA) and porcine endothelial cell seeding in improving the patency rate of vena cava grafts. Thirty-nine dogs underwent infrarenal vena cava replacement by 10 cm lengths of 8 mm I.D. ringed polytetrafluoroethylene grafts. Thirty-one grafts were seeded with 1-1.5 x 10(6) porcine aortic endothelial cells while eight were not (GIII). Of the seeded group, 16 animals received no ASA (GI), while 15 others (GII) were given ASA (325 mg) daily starting two days preoperatively and continuing until sacrifice. Venograms were performed on the fourth postoperative day. Grafts were harvested 32 days after insertion and evaluated for patency rate and endothelialized surfaces. The 32-day patency rate was significantly higher for GII than for GI and III animals (67% vs. 13 and 25% respectively). Endothelialized surface was higher in GII than Gi and III (67% vs. 16% and 18% respectively). We conclude that endothelial cell seeding alone does not prevent graft closure and that a combination of ASA and cell seeding significantly increases the patency rate of vena cava grafts. PMID- 2600124 TI - Extracranial carotid artery aneurysms. Report of two cases. AB - Two cases of extracranial carotid artery aneurysm are reported. Treatment of this uncommon but interesting vascular disorder is still under discussion even if the present tendency is to treat them actively, by reconstructive techniques. We present our surgical experience and discuss the diagnostic problems and management. PMID- 2600125 TI - Remote arterial injury. Another cause of spurious arterial spasm. AB - The need for urgent diagnosis and treatment of arterial injury is fully accepted but surgical exposure of the injured vessel is often preferred to pre-operative diagnosis by arteriography. Exposure of the artery at the site of limb injury may reveal spasm or thrombosis without evidence of direct trauma to the vessel. In that case, traction injury of the artery remote from the surgical field is likely. Commonly this affects a proximal segment of the artery but it can occur at a distal fixed point also. Attempts at thrombectomy risk further disruption of the vessel and diagnostic arteriography is required for satisfactory management. An illustrative case is presented. PMID- 2600126 TI - Vascular complications after total knee replacement. AB - Arterial complications after total knee replacement are rare. We report 2 patients who presented with ischaemia of the lower limb after ipsilateral total knee replacement. The mechanism of injury and clinical implications are discussed. PMID- 2600128 TI - Internal iliac artery graft in the management of ruptured mycotic aneurysm of the femoral artery. AB - The use of an autologous ipsilateral internal iliac artery to restore circulation after excision of a ruptured femoral aneurysm in a patient addicted to drugs is described. Autogenous vein graft was not available. The advantages of using the internal iliac artery in this situation are discussed. The use of internal iliac artery graft in this situation has not been previously described in the literature. PMID- 2600127 TI - Retrograde iliac artery dissection in Marfan's syndrome. A case report. AB - Aortic dissection is a common complication of Marfan's syndrome. We report such a patient who survived two separate dissections which both occurred shortly after uneventful pregnancies. The first dissection was a self-limiting DeBakey type III but the second commenced in the left common iliac artery and extended retrogradely into the lower abdominal aorta. This latter type of dissection does not appear to have been previously reported. PMID- 2600129 TI - Thirteen years evaluation of the Bjork-Shiley isolated mitral valve prosthesis. The Wessex experience. AB - Between 1973 and 1985, 349 patients had isolated mitral valve replacement by a Bjork-Shiley prosthesis with an overall early (30 day) mortality of 5.1%. Of the 331 survivors, 294 patients have been traced and their clinical outcome was followed for up to 13 years in order to define the long term performance of the mitral Bjork-Shiley models MBRP-standard, MBRC-convexo concave and MMSM monostrut. Cumulative follow-up extends to 6620 patient years (mean 5.75 years). The MBRP valve was implanted in 236 patients, the MBRC valve used in 44 patients and the MMSM valve inserted in 14 patients. The late mortality and morbidity was 0.8% and 0.6% per patient year at 13 years respectively. Actuarial survival rate for the whole group excluding operative deaths was 85% at 5 years, 66% at 10 years and 58.5% at 13 years. The freedom from all valve related complications at 13 years was 70.75%. Bjork-Shiley models MBRP, MBRC and MMSM mitral valve prosthesis show excellent durability with only one case of mechanical failure over a 13 year period. PMID- 2600130 TI - Prospective randomized study of St Jude Medical versus Bjork-Shiley or Starr Edwards 6120 valve prostheses in the mitral position. Three hundred and fifty seven patients operated on from 1979 to December 1983. AB - During a 5 year period (January 1979-December 1983) 357 patients were submitted to mitral valve replacement. These were performed by the same surgeon and were randomized in 2 groups: Group A consisted of 179 patients who received a St Jude Medical (SJM) prosthesis in the mitral position. Group B comprised 178 patients with a Bjork-Shiley valve (BSM) initially (113 patients from 1979 to December 1981 matched with 111 SJM) and later a Starr-Edwards 6120 valve prosthesis (65 patients matched with 63 SJM). Analysis of 21 preoperative clinical, hemodynamic data and operative variables showed the groups to be well randomized. All patients were anticoagulated postoperatively. A follow-up study was performed each year postop: at the end of 1986 there was a 35 to 95 months follow-up with a mean of 64.7 months (1596 patient years follow-up). Fifteen patients were lost to follow-up. There were 8.4% deaths related to the prosthesis in group A and 20.2% in group B (p less than 0.001). The difference was due mainly to deaths from thromboembolic complications and sudden deaths. The rate of peripheral arterial embolic complications was 2.3% in group A and 4.3% in group B per patient year (NS). The difference between the 2 groups is significant for all thromboembolic events including sudden deaths: 3.1% in group A and 7.9% per patient year in group B (p less than 0.001). There were no statistical differences in the rates of endocarditis per patient year (0.3% in group A, 0.9% in group B), reoperation (0.75% in group A, 0.89% in group B), or anticoagulant related hemorrhage (1.6% in group A, 2.4% in group B). Actuarial survival rate, including all postoperative deaths, is significantly different (p less than 0.05) at 5 years, 87.6% +/- 4.5 (group A) versus 77.4% +/- 6 (group B) and at 7 years follow-up, 83.4% +/- 6.5 (group A) versus 73.2% +/- 7.2 (group B). The probability of freedom from death and complications related to the prosthesis is significantly different (p less than 0.001) at 5 years postoperatively: 79% +/- 6.5 for group A versus 54% +/- 7.5 for group B and at 7 years: 72% +/- 7.5 (group A) versus 46% +/- 8.5 (group B). Comparison of subgroups, 113 BSM versus 111 SJM (1979-81) and 65 SE 6120 versus 63 SJM (1982-83) showed similar significant differences in the results: however there were more early deaths, valve thrombosis, valve dysfunctions and sudden late deaths in the BSM group and more peripheral arterial emboli in the SE 6120 group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600131 TI - Thrombosed Bjork-Shiley standard disc mitral valve prosthesis. AB - Between April 1980 and June 1986, 274 patients underwent mitral valve replacement (MVR) with the Bjork-Shiley (BS) standard disc mitral valve prosthesis at the American University of Beirut Medical Center (AUBMC). Eleven patients (3.9%) presented 6-41 months after surgery with prosthetic valve dysfunction due to thrombosis. Inadequate control of anticoagulation was the major factor predisposing to thrombosis in all except one. All patients had documented rheumatic valvular disease. Nine patients were operated on an emergency basis and two died before any surgical intervention was possible. Thrombectomy was performed on six patients with four survivors and MVR in three with two survivors. Two patients died intraoperatively (22%). Three pregnant patients underwent mechanical declotting; pregnancy was terminated by abortion in 2 and by caesarean section and live birth in one. We conclude that implantation of the BS mitral valve prosthesis mandates emphasis on anticoagulation and the difficulty encountered with continuous anticoagulant therapy in pregnancy. PMID- 2600132 TI - Perioperative morbidity and mortality of coronary artery surgery after the age of 70 years. AB - The aim of this study was to compare the actual perioperative (operative and hospital) morbidity and mortality of coronary bypass surgery in patients aged 70 years or older and patients aged 69 years of younger. From January 1987 to September 1988, 102 patients aged 70 years or older underwent isolated aortocoronary bypass surgery. They were compared with the younger patients operated in the same period. Preoperative, operative and postoperative data were analyzed. There was no significant difference between the mortality and morbidity of the two groups. Morbidity was evaluated according to several parameters, low cardiac output, prolonged ventilation, cerebrovascular accident, transient ischemic attacks, pulmonary problems, psychosis, renal failure, wound problems and reoperations. Because this is a limited experience it may be premature to conclude than older patients can be operated on as safely as their young counterparts, but this study shows that age is not in itself a risk factor. PMID- 2600133 TI - Effect of peroperative hypertension on 125I-albumin uptake by vein graft media. AB - Aortocoronary bypass, in use for over 20 years, is followed by lesions in 80% of vein grafts after 10 years. In 8 patients (mean age 60, SD = 7.8) before cardiopulmonary bypass, segments of saphenous vein were harvested, and following hydraulic distension (760 mmHg x 10 min), stripped of adventitia, de endothelialized, cannulated, immersed in oxygenated Krebs solution pH 7.4 37 deg C, and pressurized (100 mmHg) with 4% 125I-albumin-Evans blue for two hours. The samples were then frozen, and serially sectioned in the plane of the lumenal surface. The radioactivity of the 20 microns-thick sections was then determined, and expressed as a tissue: labelled solution concentration ratio (cpm unit volume wet tissue/cpm unit volume labelled solution). Distended portions had a higher mean transmural concentration ratio, as compared with the undistended portion; the ratio distended/undistended was 1.23, SD = 0.17, n = 8, p less than 0.01 (paired t test). This suggests alteration in the transport properties of vein interstitium by hypertension. Random histologic examination of native veins revealed no structural damage apart from age-related dystrophy of elastic fibres and intimal and medial fibrosis in grossly normal veins. These results suggest that the quality of the vein used, combined with hypertension during its preparation, may be factors in the genesis of postoperative graft failure. PMID- 2600134 TI - Complications of saphenous vein harvesting following coronary artery bypass surgery. AB - Saphenous vein harvesting, though a relatively minor part of the coronary artery bypass operation, can cause complications that may dominate the early and late postoperative course. We describe three groups of complications that are usually given little attention in the literature: complication of vein harvesting in ischemic legs, recurrent cellulitis in vein donor legs, and saphenous neuropathy. PMID- 2600135 TI - Changes in vein interstitium following distension for aortocoronary bypass. AB - Some patients who undergo aortocoronary bypass develop lesions in the graft and recurrence of symptoms. Hydraulic distension is used for preparation of veins. We have studied properties of vein interstitium, before and after peroperative distension, in 30 consecutive unselected patients. Segments of vein were studied for water content, swelling behaviour, tracer distribution, and uronic acid content. Initial water content was the same in distended and undistended vein; initial uronic acid content was slightly lower in distended veins, 8.7 (SD = 2.3) micrograms/m, n = 4 vs 10.5 (SD = 5.1) micrograms/mg dry weight, n = 6, not significant. The initial ratio, uronate/hydroxyproline was less in distended veins, 0.14 (SD = 0.05) n = 4 vs 0.19 (SD = 0.07), n = 6 in controls, not significant. Distended veins swelled less during incubation in saline. Average weight gain/initial weight was 0.65 (SD = 0.45), n = 27, and 1.1 (SD = 0.66), n = 25 in controls (p less than 0.01); change in water content/dry weight was 1.2 (SD = 1.1), n = 22, and 1.7 (SD = 1), n = 23 (p less than 0.02), in controls. Distended veins desorbed less uronic acid into the bath; 0.40 (SD = 0.2) microgram/mg wet tissue, n = 26 and 0.59 (SD = 0.3), n = 25 in controls (p less than 0.01). The pattern of uptake of two tracers 125I Serum albumin and 51Cr EDTA, was similar in both groups. These findings suggest alteration of the interstitial matrix of veins during distension. Histologic examination of glutaraldehyde-fixed tissue by light and electron microscopy revealed mural thinning and endothelial cell damage in distended veins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600136 TI - Internal mammary artery dissection: a three dimensional sternal retractor. PMID- 2600137 TI - Iterative fractionation of recycling receptors from lysosomally destined ligands in an early sorting endosome. AB - To study the fusion and separation of endocytic compartments, we have used digital image analysis to quantify the accumulation of fluorescent ligands in endosomes during continuous endocytosis for periods of 1-20 min. Fluorescently labeled transferrin (Tf) and low density lipoproteins (LDL) were used as markers of recycling receptors and lysosomally directed ligands respectively. By measuring the intensity of individual endosomes, we found that the amount of LDL per endosome increases 30-40-fold between 1 and 10 min and then plateaus. In contrast, the amount of Tf per endosome reaches a steady state within 2 min at a level that is only three to four times that at 1 min. We used pulse-chase double label methods to demonstrate that Tf cycles through the compartment in which the LDL accumulates. When both Tf and LDL are added to cells simultaneously for 2 min, nearly all endosomes contain both labels. With 2-4 min further incubation in the absence of external ligands, LDL-containing compartments become depleted of Tf as Tf is directed to para-Golgi recycling endosomes. However, if Tf is added to the medium 2-4 min after a pulse with LDL, most of the LDL-containing endosomes become labeled with Tf. The data indicate that at least 30-40 endocytic vesicles containing both Tf and LDL fuse with an endosomal compartment over a period of 5-10 min. LDL accumulates within this compartment and Tf is simultaneously removed. Simple mathematical models suggest that this type of iterative fractionation can lead to very high efficiency sorting. PMID- 2600139 TI - Transferrin receptors on the surfaces of retinal pigment epithelial cells are associated with the cytoskeleton. AB - Retinal pigment epithelial cells, derived from human donor eyes, have been grown in culture as monolayers on membrane filters or plastic surfaces and shown to possess transferrin receptors with a monomeric molecular mass of 93,000. These receptors internalize 125I-labelled transferrin and recycle it to the surrounding medium in a similar manner to other cell types. Scatchard analyses show that there are about 100,000 high-affinity receptors on the surface of each cell and most of these receptors are associated with the cytoskeleton. In total cell extracts, there are additional low-affinity binding sites that do not appear to be strongly associated with the cytoskeleton. The apparent interaction of transferrin receptors with the cytoskeleton was confirmed in two ways: first, using 200 kV electron microscopy for stereo analyses, skeleton-associated transferrin receptors were detected by a monoclonal anti-receptor antibody and a colloidal gold-conjugated second antibody after Triton X-100 extraction of pigment epithelial cells grown directly on laminin-coated gold grids; and, second, when cell surface receptors were labelled with radioiodinated transferrin and then incubated for various periods of time, the labelled transferrin was observed to move from a Triton X-100-insoluble fraction (a putative cytoskeletal compartment) to a Triton-soluble compartment that was not associated with the cytoskeleton. Using either horseradish peroxidase or colloidal gold-labelled transferrin, it has been shown that basolateral and apical surface-located receptors participate in receptor-mediated endocytosis via clathrin-coated pits, endosomes and tubular structures. Initially, transferrin internalized from the apical surface is observed in small endosomes that often appear to be embedded in an apical layer of microfilaments. From these peripheral regions of the cells, the labelled receptors move to larger endosomes and multivesicular bodies deeper in the cytoplasm. These structures have no apparent association with cytoskeletal elements. PMID- 2600138 TI - Selective secretion of alternatively spliced fibronectin variants. AB - We demonstrate that the alternatively spliced variable (V) region of fibronectin (FN) is required for secretion of FN dimers during biosynthesis. Alternative splicing of the V segment of the rat FN transcript generates three subunit variants (V120, V95, V0) that differ by the inclusion or omission of an additional 120 or 95 amino acids. We are exploring the functions of this segment by expressing variant cDNAs in normal and transformed fibroblasts. Like FN itself, the cDNA-encoded polypeptides (deminectins [DNs]) containing the V120 or V95 segment are efficiently secreted as disulfide-bonded homodimers. However, few homodimers of DNs lacking this region, V0 DNs, are secreted. V0 homodimers do form inside the cell, as demonstrated by biosynthetic analyses of dimer formation and secretion using pulse-chase and time course experiments, but these dimers seldom reach the cell surface and are probably degraded intracellularly. Coexpression of V0 and V120 subunits results in intracellular formation of three types of dimers, V0-V0, V0-V120, and V120-V120, but only the V120-containing dimers are secreted. This selective retention of V0 homodimers indicates that the V region is required for formation and secretion of native FN dimers. In an analogous in vivo situation, we show that plasma FN also lacks V0-V0 dimers and consists of V0-V+ and V+-V+ combinations. Dissection of V region sequences by deletion mapping localizes the major site involved in DN dimer secretion to an 18 amino acid segment within V95. In addition, high levels of dimer secretion can be restored by insertion of V into a heterologous site 10 kD COOH terminal to its normal location. We discuss the potential role of intracellular protein-protein interactions in FN dimer formation. PMID- 2600140 TI - Ductal epithelial cells cultured from human foetal epididymis and vas deferens: relevance to sterility in cystic fibrosis. AB - A tissue culture system for epithelial cells derived from male human foetal genital ducts has been established. The cells show morphological and biochemical characteristics of ductal epithelial cells, and can be passaged and maintained in culture for considerable periods of time. These cells will provide a suitable system for investigating, by electrophysiological, biochemical and molecular biological methods, the cause of sterility in cystic fibrosis. PMID- 2600141 TI - Preparation of adsorbents for affinity chromatography using TSKgel Tresyl Toyopearl 650M. AB - The optimum conditions for the coupling of proteins were investigated using TSKgel Tresyl-Toyopearl 650M. They were dependent on the proteins coupled. For example, when soybean trypsin inhibitor was coupled at pH 8 the coupling was completed within 1 h and the subsequent adsorption capacity for trypsin was maximal. Longer coupling times decreased the adsorption capacity due to multi point attachment. The adsorbents obtained were successfully used for affinity chromatography in a short time. PMID- 2600142 TI - Monoclonal antibody-mediated clean-up procedure for the high-performance liquid chromatographic analysis of chloramphenicol in milk and eggs. AB - A simple, rapid and specific sample preparation method based on antibody-mediated clean-up for the determination of chloramphenicol (CAP) in milk and eggs was developed. Skimmed milk and centrifuged egg homogenates were filtered and directly applied to immunoaffinity columns which were prepared by coupling monoclonal antibodies against CAP to a carbonyldiimidazole-activated support. Using a 0.2 M glycine, 0.5 M NaCl (pH 2.8) solution as an eluent, the immunoaffinity columns can be used more than 30 times without a decrease in column capacity. In subsequent high-performance liquid chromatographic analysis, no matrix interferences were observed. Good recoveries were obtained at spiking levels of 1-100 micrograms kg-1. Due to the high specificity of the clean-up procedure, the limit of detection can be lowered by increasing the test portion. Concerning milk, the limit of detection was successfully lowered to 20 ng kg-1 by increasing the test portion to 11 (recovery 99%). The method was applied to eggs produced by hens treated with CAP. The results are compared with those obtained by solid-phase extraction using silica gel. PMID- 2600143 TI - Chromatographic behaviour and determination of orellanine, a toxin from the mushroom Cortinarius orellanus. PMID- 2600144 TI - Indirect determination of O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate in air at low concentrations. AB - This paper describes an indirect method for the quantification of the toxic military agent O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) in the vapor state in air or other similar gases at ng/m3 levels. The method begins with the passage of a gaseous sample through a filter impregnated with silver fluoride to convert the VX vapor to ethyl methylphosphonofluoridate. The latter compound is then trapped on a bed of Chromosorb 106, transferred to a smaller bed of the same sorbent, and desorbed thermally into a gas chromatograph equipped with a flame-photometric detector. The method is comparable in sensitivity to the principal alternative method, which is based on cholinesterase inhibition, and it is less subject to interference from common organic solvents and other cholinesterase inhibitors. The detection limit was found to be limited by, and therefore dependent on, the nature and extent of any background substances that produced a significant chromatographic signal or response at the retention time of the analyte. In the absence of such substances, the instrument provided a response to 0.19 ng of VX that was thirty times larger than the peak-to-peak noise amplitude on the chromatographic base line. Moreover, the method bias (i.e., 100% minus the percent VX recovery) was found to depend on VX concentration, with estimates of agent recovery ranging from 83% at a VX concentration of 0.67 ng/m3 to 104% at a concentration of 0.084 ng/m3. The relative standard deviation varied with VX concentration and with the nature of the test that was performed to estimate it. It ranged from 2.1% in one VX vapor challenge test to 17% in an experiment involving spiked sampling tubes, and it was generally lower at the higher VX test concentrations. PMID- 2600145 TI - Retention behavior of cardiac steroids using cyclodextrin in the mobile phase in high-performance liquid chromatography. AB - The retention behaviour of twenty cardiac steroids and four fluorescent derivatives was examined by the addition of cyclodextrin to the mobile phase in reversed-phase high-performance liquid chromatography. The addition of a suitable cyclodextrin improved the separation of isomeric cardiac steroids. The steroid A/B ring junction is the most important factor in the choice of the optimum cyclodextrin to be added; the C/D ring junction is less important. The hydroxyl group at the 3- or 12-position of the steroid enhanced the changes in retention times of these compounds. The effect of an unsaturated lactone ring at the 17 beta-position on the retention in the presence of cyclodextrin was also determined with cardenolide (five-membered ring) and bufadienolide (six-membered ring) but little difference was observed. Isomeric cardiac steroids, whose separation has not been done by the conventional method, were clearly separated by this method. The fluorescence intensity of 3-(1-anthroyl)-cardiac steroid was enhanced by the addition of cyclodextrin to the mobile phase. PMID- 2600146 TI - Multiresidue procedures for the determination of chlorinated dibenzodioxins and dibenzofurans in a variety of foods using capillary gas chromatography-electron capture detection. AB - Multiresidue digestion-extraction procedures for the determination of chlorinated dioxins and furans in a wide variety of products are presented. Procedure selection is dependent upon the residue(s) of interest, and on the fat content of the product. Additional cleanup is accomplished using column chromatography and a Florisil trap. The separation of residues is achieved by fraction collection off of two high-performance liquid chromatographic systems. Capillary gas chromatography employing electron-capture detection is used for quantitation. The extracts are suitable for gas chromatography mass spectrometry or gas chromatography with Hall electrolytic conductivity detection. Results of analysis, recovery data, and interlaboratory comparisons are presented. Spike recoveries will typically average 90% +/- 10%. PMID- 2600147 TI - Isolation of turbot (Scophthalmus maximus) vitellogenin by high-performance anion exchange chromatography. AB - The use of high-performance anion-exchange chromatography on a Mono Q column for isolation of a glycolipophosphoprotein, vitellogenin, from turbot plasma has been evaluated. The method is an effective, rapid one-step procedure, which gives a pure preparation of vitellogenin as assessed by electrophoresis, [32P]orthophosphate incorporation and amino acid composition. PMID- 2600148 TI - Preparative high-performance liquid chromatography using detection by thermospray mass spectrometry. PMID- 2600149 TI - Quantitative determination of sulfanilamide in sodium sulfacetamide raw material and ophthalmic solutions by high-performance liquid chromatography. PMID- 2600150 TI - Lanthanide luminescence quenching as a detection method in ion chromatography. Chromate in surface and drinking water. AB - Dynamic quenching of Eu(III) and Tb(III) luminescence by inorganic anions as a detection method in ion chromatography was investigated. To obtain a high luminescence intensity, lanthanide(III) complexes are formed with ligands which make indirect excitation of the ions possible. Only a few anions (e.g., nitrite, chromate) induce efficient dynamic luminescence quenching. Chromate is an efficient quencher of Tb-acac luminescence. Samples of tap water and surface water, spiked with chromate, were injected into a high-performance liquid chromatographic system with post-column addition of the luminescent complex. In this way, a detection limit of 1.1 . 10(-7) M (13 ppb) of chromate could be obtained. PMID- 2600151 TI - Alumina as stationary phase for ion chromatography and column-coupling techniques. AB - Columns packed with alumina were combined with common anion-exchange columns and applied to the ion chromatographic determination of sulphate in brines and biological fluids and for the trace determination of iodide in mineral waters and fruit juice samples. Alumina was found to be a highly selective stationary phase for the preconcentration of sulphate from complex matrices. Further, owing to its selectivity, which is different from that of R4N+-type anion-exchange materials, it is well suited for on-line column-coupling techniques. In this way sample clean-up can be minimized, and the sensitivity of the chromatographic system allows determinations of iodide down to the low ppb range. PMID- 2600152 TI - Determination of cations in tear fluid samples by non-suppressed ion chromatography with indirect UV detection. PMID- 2600153 TI - Modification of a Dionex System 12 ion chromatograph for sequential determination of the main components in atmospheric precipitation. AB - A modification of a Dionex System 12 ion chromatograph is described which enables organic anions (acetate and formate), inorganic cations (ammonium, sodium and potassium) and inorganic anions (chloride, nitrate and sulphate) to be determined sequentially in one measuring procedure. The modified instrument consists of a programmable controller unit, a conductimetric meter, two conductimetric detectors of the Dionex System 12 ion chromatograph, the HPIC-AS4A and HPIC-CS3 modern separation units, AMMS-1 and CMMS-1 micro-membrane suppressor columns, a unique system of valves from Dionex and two dual pumps from Biotronik. The limits of detection are between about 1 and 3 micrograms/l for chloride, nitrate and sulphate and between about 2 and 10 micrograms/l for acetate, formate, ammonium, sodium and potassium. The reliability of the method was demonstrated by analysing two NBS simulated rain water Standard Reference Materials. Some examples are given of the application of the method to the sequential determination of the main precipitation components in typical samples from urban and rural regions of the F.R.G. The ion concentrations varied between about 0.02 and 300 mg/l. PMID- 2600154 TI - Focus on outcomes. PMID- 2600155 TI - Unit-based outcomes developed through nursing diagnoses. PMID- 2600156 TI - From process to outcome in infection control. PMID- 2600157 TI - Measuring the impact of nursing interventions on patient outcomes--the challenge of the 1990s. PMID- 2600159 TI - Evaluating structure, process, and outcome indicators in ambulatory care: the AMBUQUAL approach. PMID- 2600158 TI - Monitoring patient outcomes in an oncology unit. PMID- 2600160 TI - Developing standards and criteria: family health nurse specialists in a nursing center. PMID- 2600161 TI - Orthodontic office design. Hallways. PMID- 2600162 TI - Correction of tongue-thrust swallowing habits. PMID- 2600163 TI - Evaluation of gloves for orthodontic use. PMID- 2600164 TI - The modular palatal disjunctor appliance. PMID- 2600165 TI - Clinical and instrumental functional analysis for diagnosis and treatment planning. Part 8: Case studies in CADIAX. PMID- 2600166 TI - Precision lingual arches. Active applications. PMID- 2600167 TI - Practice planning: a team effort. PMID- 2600168 TI - Clinical and instrumental functional analysis for diagnosis and treatment planning. Part 9. Removable splint therapy. PMID- 2600169 TI - Treatment of failed open reduction for congenital dislocation of the hip. AB - Twenty-three patients with 25 involved hips underwent repeat open reduction after previous unsuccessful attempts at open reduction for congenital dislocation of the hip (CDH). All hips ultimately were reduced at a mean age of 2 years 10 months (range 10 months to 7 years 3 months). On review, we noted that 15 of the hips were never concentrically reduced at the first procedure, and seven of these hips had undergone simultaneous Salter osteotomy. The most common cause of failure was improper exposure and release of the tight inferior capsule and transverse acetabular ligament, which blocked complete reduction. A vascular necrosis was documented in 44% of the hips, with a lateral physeal growth disturbance in four hips, a central physeal growth arrest in four hips, and complete femoral head necrosis in three hips. PMID- 2600170 TI - Congenital dislocation of the hip: acetabular deficiency in adolescence (absence of the lateral acetabular epiphysis) after limbectomy in infancy. AB - Acetabular development in adolescence was assessed in 61 patients with congenital dislocation of the hip (CDH). Limbectomy was performed in 31; in these, the lateral acetabular (iliac) epiphysis failed to appear by age 13 years. This failure was associated with loss of cover of the femoral head in patients followed up until the third decade. The lateral acetabular epiphysis appeared in all remaining patients in whom reduction was achieved without limbectomy. Acetabular development in adolescence is affected adversely by limbectomy; this is due at least in part to absence of the lateral acetabular epiphysis. PMID- 2600171 TI - Parental noncompliance with Pavlik harness treatment of infantile hip problems. AB - This study reviews use of the Pavlik harness from the parents' perspective. Questionnaires were answered by the parents of 32 children who had been treated with a Pavlik harness for congenital hip problems. Of 27 patients who were initially treated by the authors, only the parents of two children claimed that they followed the physicians's orders exactly. However, only one of the four treatment failures could be directly attributed to parental noncompliance. Specific problems with the harness such as bathing, inability to fit into car seats, and clothing led to the noncompliance in many cases. There was no relationship between the parents' age, financial background, or education and their compliance. PMID- 2600172 TI - Follow-up study of slipped capital femoral epiphysis. AB - We studied 50 hips in 46 patients with slipped capital femoral epiphysis (SCFE). Seven patients with acute cases were treated by closed reduction with excellent results and without any known complication. The cases in the remaining 39 patients were of the chronic type. The method of treatment was determined according to the posterior tilting angle: in situ pinning for angles less than 30 degrees, intertrochanteric osteotomy for angles between 30 and 60 degrees, and subcapital wedge osteotomy for angles greater than 60 degrees. Chondrolysis was observed in one case treated with intertrochanteric osteotomy, and chondrolysis and avascular necrosis occurred in one case of subcapital wedge osteotomy. PMID- 2600173 TI - Avascular necrosis of the hip in multiple epiphyseal dysplasia. AB - We observed radiographic changes of avascular necrosis (AVN) of the capital femoral epiphysis in 9 hips of 11 patients with multiple epiphyseal dysplasia (MED). Plain roentgenography, bone scintigraphy, and magnetic resonance imaging (MRI) studies all revealed characteristic asymmetric changes in the presence of AVN superimposed on dysplastic femoral heads. PMID- 2600174 TI - Effect of posterior spinal fusion on spinal balance in idiopathic scoliosis. AB - We analyzed the influence of posterior spinal fusion with Harrington rod instrumentation on spinal balance in 85 patients with primary thoracic curve patterns. Utilizing roentgenographic techniques of measurement, spinal decompensation was improved measurably in 64% of the patients, and lateral trunk shift improved in 82% of the patients with preoperative alterations of spinal balance. PMID- 2600175 TI - Threaded K-wire spinous process fixation of the axis for modified Gallie fusion in children and adolescents. AB - A retrospective analysis of a technique for achieving atlantoaxial arthrodesis was performed. Fourteen patients underwent a modified Gallie technique, and all patients achieved successful arthrodesis with minimal restriction in rotation of the neck postoperatively. No patients showed neurologic deterioration. Fixation of a threaded K-wire to the spinous process of the axis improved the stability of the wiring technique, and we have been very successful in achieving atlantoaxial arthrodesis in the pediatric population. PMID- 2600176 TI - Biological factors and predictability of bracing in adolescent idiopathic scoliosis. AB - Biological factors that could have a predictive value in treating idiopathic scoliosis by brace were studied in 107 patients (102 girls and 5 boys). The mean age of the patients was 14 years 6 months, and the mean Cobb angle of the curves was 36 degrees at start of treatment. The Boston brace was used for an average of 1 year 6 months, and mean follow-up time after weaning was 3 years. Scoliosis with an apex of Th 10-12 proved to be the most favorable for the final result, with a mean correction of 2 degrees. All other curves remained unchanged. Patients who had a period of rapid growth just before or during treatment had a better final result than the others. The final result was also better when treatment was started before menarche. PMID- 2600177 TI - Arthrodesis of the paralytic shoulder. AB - Five children, aged 7-15 years, with brachial palsies and flail shoulders, had fusions performed. Four of the five had improved function; however, there was progressive loss of fused abduction position over time. PMID- 2600178 TI - Nonunion of slightly displaced fractures of the lateral humeral condyle in children: an update. AB - Inadequate treatment continues to be the leading cause of nonunion of slightly displaced fractures of pediatric lateral humeral condyles, despite references to prevention in the orthopaedic literature. In most cases, the elbow was established nonunion can be salvaged by early stabilization and bone grafting, provided that the fragment is in acceptable position and the growth plate of the condylar fragment is open. Procrastination may allow the physis of the condylar fragment to close prematurely, preemptying the golden opportunity to salvage the child's elbow. The author has collected 23 similar cases from correspondence with 17 orthopaedic surgeons. PMID- 2600179 TI - Calcaneal gait in spastic diplegia after heel cord lengthening: a study with gait analysis. AB - Calcaneal gait or deformity can be a significant complication after heel cord lengthening. After heel cord lengthening, 20 children with spastic diplegia were evaluated by gait analysis to define calcaneal gait objectively and describe associated morbidity. Mean age was 5 years 2 months (range 2 years 7 months to 8 years 2 months), and mean length of follow-up was 5 years 8 months (range 1 years 1 month 11 year 3 months). Calcaneal gait was defined as dorsiflexion 1 SD beyond the mean in the sagittal plane for all phases of stance. Increased ankle dorsiflexion during mid-stance most accurately predicts calcaneal gait. Through gait analysis, a 30% (6 of 20) prevalence of calcaneal gait suggests that an increased incidence of calcaneal gait may be present after heel cord lengthening. PMID- 2600180 TI - Effects of ankle-foot orthoses on the gait of children. AB - Gait analysis was performed on five normal children walking barefoot with bilateral double-upright ankle-foot orthoses (AFOs) and with plastic AFOs. When orthoses were worn, walking speed and cadence were reduced and quadriceps EMG timing was prolonged. Changes in lower extremity motions and torques were observed. The metal-and-leather AFOs impaired normal walking, more than the plastic orthoses. This study provides baseline information for evaluation of new orthotic designs and materials for children. In clinical practice, this information may be useful in selection of orthotic materials for some patients. PMID- 2600181 TI - Chronic idiopathic hyperphosphatasia and fibrous dysplasia in the same child. AB - A generalized skeletal dysplasia with features of chronic idiopathic hyperphosphatasia and fibrous dysplasia of the mandible were observed in a 6-year old child. The abnormal development of the bones resulted from enhanced remodeling and the failure of mature bone to form. The occurrence of the two lesions in the same child and a review of the literature support the hypothesis that pathogenesis of fibrous dysplasia and idiopathic hyperphosphatasia reflect an underlying common defect in the control of bone cell activity. PMID- 2600182 TI - Percutaneous quadriceps recession: a technique for management of congenital hyperextension deformities of the knee in the neonate. AB - Percutaneous quadriceps recession was compared with open quadricepsplasty in the Finder's type 5 category of congenital hyperextension deformities. Six open quadricepsplasties and six percutaneous recessions were performed between the ages of 5 and 58 days. Follow-up averaged 2 years 3 months. All knees remained reduced and maintained an improved range of motion (ROM). Percutaneous recession avoids a long incision, requires less dissection and surgical time, and has a shorter healing time. When performed in the neonate, percutaneous recession eases management of the child and treatment of coexistent deformities. PMID- 2600183 TI - Elevated growth velocity in children with Perthes' disease. PMID- 2600184 TI - A Social Environment Inventory for the pediatric office. AB - Exposure to psychosocial stressors is associated with deleterious physical and mental health outcomes among children and adults, as well as with school-related and behavioral problems among children. However, research and intervention in this area have been hampered by the lack of a valid measurement tool to assess exposure to stressors among mothers. This paper reports on the development and testing of a self-administered questionnaire for use in the pediatric setting to assess maternal exposure to stressors. The questionnaire was developed to facilitate the early identification of mothers exposed to high levels of stressors, since exposure to stressors often precedes the onset of problems. Early identification of mothers and children, in the pediatric office, could facilitate the prevention of various behavioral, school, and other problems among children. PMID- 2600185 TI - A five-year follow-up of preschool children diagnosed as having an atypical pervasive developmental disorder. AB - Twelve of eighteen preschool children, previously diagnosed as having an atypical pervasive developmental disorder (APDD), using the third edition of the Diagnostic and Statistical Manual (DSM-III) of the American Psychiatric Association, were followed up 5 years later. The follow-up consisted of a pediatric neurodevelopmental evaluation and the administration of the Personality Inventory for Children (PIC), and a scale derived from the criteria for an autistic disorder (AD) in the revised third edition of the Diagnostic and Statistical Manual (DSM-III-R). The children continued to have significant emotional, social, and cognitive problems at follow-up. Almost all required some form of therapeutic intervention, and many received multiple interventions. A broader range of symptoms (including positive symptoms of schizophrenia and signs of affective and anxiety disorders) were noted. A comparison of DSM-III and DSM III-R criteria for autism with this population revealed a lack of reliability in diagnoses between systems, both with respect to the more specific diagnosis ("autism") and the less specific atypical diagnoses. The authors discuss the implications of these findings with respect to the interpretation of future follow-up studies of autistic and atypical children. PMID- 2600186 TI - The effects of intraventricular hemorrhage on functional communication skills in preterm toddlers. AB - A group of 24-month-old preterm toddlers (n = 27) were subdivided into three groups according to their early specific medical complications [i.e., respiratory distress syndrome (RDS), without intraventricular hemorrhage (IVH), IVH (Grades I and II), and IVH (Grades III and IV]) and were matched to a group of full-term toddlers (n = 10) on socioeconomic status and mental and receptive language age. We evaluated (1) the effects of IVH on functional use of language (e.g., speech acts), and (2) the relationship of mothers' verbal attempts to stimulate children's interest in topics and toys with the communication behaviors used by the children. The preterm groups used verbalizations and gestures less frequently to express a range of functions, but were comparable to the full-term children in their use of communicative acts that served to continue interactions. Although child behaviors did not differ in relation to specific medical complications, these differences were apparent in the mothers' behavior patterns and in the relationships between mother and child behavior. Mothers' verbal maintaining behavior was strongly associated with children's use of language for the full term and two lower risk preterm groups, but not the higher risk IVH (Grades III and IV) group. The mothers of the IVH (Grades III and IV) group showed high responsiveness to lower level child behaviors, a pattern that was not apparent in the other preterm groups for lower risk children who showed comparable delays in their functional communication development. PMID- 2600187 TI - The use of stimulant medication with children. PMID- 2600188 TI - Youth and America's future: the forgotten half. AB - The William T. Grant Foundation's Commission on Youth and America's Future was created to review existing research on problems facing young people in America today, and to make policy recommendations based upon the results of that research. The Commission found that fewer economic opportunities are available today, especially to non-college-bound young people, than was the case even a decade ago. This situation has had an adverse effect on the youths themselves, their families, and ultimately, on American society as a whole. Many problem behaviors have their origin in the reduced opportunities which young people face today. The Commission cites a number of programs that show promise to ameliorate behavioral and economic problems of youth, and urges government, business, and other private agencies to join together in implementing and expanding existing programs (such as the Job Training Partnership Program) and in creating new ones (such as the Youth Opportunities Demonstration Act). Society needs to recognize the important role which youth can play as good citizens by providing opportunities for them to give needed services to the community. PMID- 2600189 TI - Psychosocial screening in pediatric practice: identifying high-risk children. PMID- 2600190 TI - Sulindac kinetics and effects on renal function and prostaglandin excretion in renal insufficiency. AB - The purpose of this study was to evaluate the pharmacokinetics of sulindac, a purported "renal sparing" nonsteroidal anti-inflammatory drug, and its effects on renal function and prostaglandin excretion in patients with reduced glomerular filtration rate. Twelve female patients (glomerular filtration rate 37 +/- 4 mL/min) were treated with sulindac 200 mg bid for 11 days. Urinary PGE2, 6-keto PGF1 alpha and serum thromboxane (TxB2) generation were measured by radioimmunoassay (RIA) following extraction on C-18 columns. Glomerular filtration rate and effective renal plasma flow were measured by 99TC-DPTA and 131I-para-aminohippuric acid clearance. In six patients serum and urine levels of sulindac and its metabolites were measured by high-pressure liquid chromatography (HPLC). Sulindac was rapidly absorbed and converted to sulindac sulfide with peak levels 2 hours after a single dose, but steady state levels were not reached prior to drug discontinuation. Sulindac sulfide AUC (0-5 hours micrograms min/mL) progressively increased from 382 to 3,030 on day 11. It did not appear in the urine. Baseline urinary PGE2 and 6-keto-PGF1 alpha excretion were 23.8 +/- 5.6 and 18.9 +/- 2.7 ng/hr respectively and were reduced by 68% and 47% by day 4 of therapy. TxB2 generation fell by 34% after one dose and by 67% by day 11. There was a significant increase in serum creatinine from 1.88 +/- 0.13 mg/dl before treatment to 2.16 +/- 0.15 mg/dL (P less than .05) after eleven days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600191 TI - Bayesian forecasting of APTT response to continuously infused heparin with and without warfarin administration. PMID- 2600192 TI - New drugs: first time in man. PMID- 2600193 TI - Availability and timing of new drugs in Israel: analysis and international comparison. AB - Whereas the latest data suggest that the number of new chemical entities (NCE) launches worldwide may be on the increase, both recent and longer term data show a decline in the rate of NCE introductions into Israel. In terms of percentage availability, only 30% of NCEs available worldwide during 1978-1987 were introduced in Israel during the same period, compared with 42% for the U.S.A. In both countries there has been a decreasing percentage availability since 1983/84. The percentage availability of commercially significant NCEs was greater (47%) compared to all NCEs introduced in Israel. Whereas in the U.S.A. the lower the therapeutic rating the higher the proportion of NCEs, in Israel the B- and C rated drugs were equally represented. NCEs with an A-rating had a similar share of all NCEs (ca 15%) in both countries. The average time lag for NCEs launched worldwide to reach Israel during 1978-1987 was 4 to 5 years, but in recent years there has been a considerable decline. Commercially significant NCEs introduced in Israel had on average a shorter time lag of 0.5 years than the average for all NCEs introduced. In spite of a preponderance of NCEs first launched in the U.S.A. there was on average a slight relative lag into the U.S.A. compared to Israel. This was probably due to there being a number of NCEs first introduced in Israel with a long delay before they were subsequently approved in the U.S.A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600194 TI - Differences in oral verapamil absorption as a function of time of day. AB - As part of a multiple dose bioavailability study, 80-mg verapamil hydrochloride tablets were administered to healthy subjects every 8 hours for 15 doses. Statistically significant successive decreases in verapamil maximum plasma concentrations (Cmax) and area under the concentration-time curve (AUC) values were observed corresponding to dosing at 8 AM, 4 PM, and 12 AM. Mean Cmax and AUC values from the 12 AM dose were decreased 36% and 30%, respectively, relative to those from the 8 AM dose. Similar effects on norverapamil pharmacokinetics were observed. Decreased Cmax and AUC values show that verapamil absorption is influenced by the time of day when doses are administered. Pharmacokinetic simulation results suggest that the rate of absorption is reduced approximately by one half and two thirds during the 4 PM and 12 AM dosing intervals, respectively, relative to the 8 AM dosing interval. The reductions in verapamil absorption as a function of time of administration observed in this study may in part explain previous reports of reduced antihypertensive effect during evening and night hours as compared to daytime hours. PMID- 2600195 TI - Dose dependent effect of diltiazem on the pharmacokinetics of nifedipine. AB - The effect of diltiazem pretreatment on the pharmacokinetics of nifedipine were determined in six healthy male volunteers. Placebo or diltiazem (30 mg and 90 mg) was given orally three times daily for 3 days in a double-blind, Latin square method. On the fourth day, a 20-mg nifedipine was given orally 1 hour after the last dose of placebo or diltiazem. The mean elimination half-life of nifedipine prolonged significantly following diltiazem (2.54 hours on placebo vs 3.40 hours on 30 mg diltiazem and 3.47 on 90 mg diltiazem, both P less than .01). The mean AUC of nifedipine increased during diltiazem (1726.6 nmol X hr/ml on placebo vs 3838.0 on 30 mg diltiazem, and 5370.0 on 90 mg diltiazem, both P less than .05, 30 mg vs 90 mg, 0.1 less than P less than .05). The ratio of the AUC of primary metabolite (nitropyridine form) to the AUC of nifedipine was reduced by diltiazem pretreatment in a dose-dependent manner. ICG clearance was not influenced following diltiazem. These results indicate that diltiazem dose-dependently alters the pharmacokinetic profiles of nifedipine. The ICG clearance test showed that the liver blood flow did not decrease during diltiazem therapy, therefore, the reduction in the metabolic clearance of nifedipine might be caused by inhibiting effect of diltiazem on the activity of drug oxidizing enzymes. PMID- 2600196 TI - Phonological space in the speech of the hearing impaired. AB - The vowels /a/, /i/, and /u/ form the extreme points of vowel triangle in Kannada language. First and second formant frequencies of these vowels were measured to determine the phonological space in the speech of the 30 deaf subjects and 30 normally hearing subjects. The phonological space was found to be reduced in the speech of the hearing-impaired subjects, and the reduction was primarily due to the lowering of the second formant of the vowel /i/. Therapeutic implications have been drawn. PMID- 2600197 TI - Performance of university students on the Fullerton subtest of idioms. AB - The study examined the performance of 71 university students on the Fullerton Language Test for Adolescents subtest on Idioms. The subjects were assigned to one of three age categories, and the performances of the groups were compared. The results demonstrated that 51% of the 18-21-year-old group fell within the "Competence Range" for this subtest, while 84% of the 22-29-year-old group and 91% of the 30+ year-old group fell within this range. As chronological age increased, performance improved. PMID- 2600198 TI - The use of stress by language-impaired children. AB - This investigation was conducted to identify the stressing patterns of language impaired children in the early stages of language acquisition. Based on Wieman's (1976) work with children who were acquiring language normally, it had been expected that the subjects of this study would tend to stress the new information in two-word utterances. Only one of the five preschool language-impaired children used such a pattern. Three subjects tended to stress words in the final position and one of the subjects' preference was unclear. The results, although preliminary, provide support for the contention that language-impaired children may differ from normal children in their use of stress. PMID- 2600199 TI - A longitudinal study of the prevalence of voice disorders in children from a rural school division. AB - In a mass screening of children ages 6-10 in a rural school division, 203 children were identified as showing a voice deviation. One year later a retesting of 178 of these children showed that 39.9% still showed a voice disorder. Four years later 50 of these children were still available in the same school system; 38% of them still showed a voice disorder. Virtually none of these children were referred to the otolaryngologist for an ENT evaluation or to the speech-language pathologist for voice rehabilitation. Results indicate that, for many of these children, the voice disorders do not "clear up" through maturation alone. PMID- 2600200 TI - Clinical validation of a nutritional risk index. AB - This research assessed the clinical validity of a nutritional risk index (NRI). Subjects were 377 male veterans, aged 55+, attending general medicine and geriatric outpatient clinics. Data were collected by personal interviews, anthropometric measurements, laboratory assay of nutritional parameters, three day food records, and medical record reviews. Although the results showed that the NRI correlated significantly with only two nutritional measures (body mass index, total energy intake), critical values or threshold levels of NRI were identified that significantly discriminated low risk from high risk patients on four nutritional parameters (body mass index, total energy intake, laboratory risk, and medications risk). It was concluded that the NRI is a valid measure of health status and contains a nutritional dimension. PMID- 2600201 TI - Risk factor knowledge, status, and change in a community screening project. AB - This report describes a community-based cardiovascular risk-reduction program which targeted high-risk individuals. A total of 1,471 individuals participated and were screened for blood pressure, fasting serum cholesterol, blood glucose level, and appearance of the serum. These individuals also completed a questionnaire regarding their knowledge of heart disease. Overall, 522 (35.5%) individuals had a cholesterol level of 240+ mg/dl; 261 (17.7%) had hypertension; 118 (8%) had a glucose level of 120+ mg/100 ml blood; 266 (18.1%) smoked; and the serum was evaluated as "turbid" or "lipemic" in 105 (7.1%). Therefore, of the 1,471 individuals examined, 733 (49.8%) could be considered "at risk" due to the presence of one or more risk factors. Interestingly, 73% of respondents knew their blood pressure, whereas only 15% and 12%, respectively, knew their cholesterol and glucose levels. Eighty percent of the sample knew that smoking, hypertension, and cholesterol were risk factors, but only 50% of the sample identified diabetes as an independent risk factor. Contrary to expectation, knowledge of heart disease and diabetes was not related to either initial level or change in cholesterol at 18-month retest. Overall, these results indicate that a community screening program can identify high risk individuals at a relatively low cost, and that knowledge of risk factors and disease is not related to initial risk status or self-initiated change in risk status. PMID- 2600202 TI - Review of a health fair screening program in Mid-Michigan. AB - Using sociodemographic data and findings from an evaluation survey, a Mid Michigan health fair screening program is reviewed over a seven year period (1981 1987). Most participants were older adults, and nearly two-thirds were women. Very few participants named the media as a reason for attending the health fairs at which the screenings were given. Many had seen a physician within the past two years, yet very few reported that they had had a complete check-up. The implications of these findings and a rationale for health fairs as a mechanism for screening are discussed. PMID- 2600203 TI - Community-based health promotion: a survey of churches, labor unions, supermarkets, and restaurants. AB - A telephone survey of randomly-sampled churches, labor unions, supermarkets and restaurants was conducted in San Diego, California to determine the level of health promotion activities offered for members and customers. Nearly two-thirds of the churches offered health promotion programs, the bulk of which were single educational sessions. A similar proportion of labor unions reported programs, and most of them consisted of the distribution of materials and single-session group meetings. About one-third of the supermarkets reported activities, with most of these being the distribution of brochures. Similarly, about one-third of restaurants reported programs, which primarily consisted of the enforcement of no smoking regulations. Very few organizations evaluated programs or desired assistance from health professionals. It was concluded that while secular health promotion programs are common and are available to many people, their quality and effectiveness are unknown. These findings present a challenge for public health professionals and agencies. PMID- 2600204 TI - Assessing risks and preventing disease from environmental chemicals. AB - In the last 25 years there has been considerable concern expressed about the extent to which chemical agents in the ambient and work environments are contributing to the causation of disease. This concern is a logical extension of our increased knowledge of the real and potential effects of environmental chemicals and the methodological difficulties in applying new knowledge that could help prevent environmentally induced disease. Chemical risk assessment offers an approach to estimating risks and involves consideration of relevant information including identification of chemical hazards, evaluation of the dose response relationship, estimation of exposure and finally, risk characterization. Particularly significant uncertainties which are inherent in use of this and other risk models include animal-human and low dose-high dose extrapolation and estimation of exposure. Community public health risks from exposure to environmental chemicals appear to be small relative to other public health risks based on information related to cancer trends, dietary intake of synthetic chemicals, assessment data on substances such as DDT and "dioxin," public health effects of hazardous waste sites and contextual considerations. Because of inherent uncertainty in the chemical risk assessment process, however, we need to apply what methods are available in our efforts to prevent disease induced by environmental chemicals. There are a number of societal strategies which can contribute to overall reduction of risk from environmental chemicals. These include acquisition of information on environmental risk including toxicity, intensity and extensity of exposure, biological monitoring, disease surveillance, improvement in epidemiological methods, control of environmental chemical exposures, and dissemination of hazardous chemical information. Responsible environmental risk communication and information transfer appear to be among the most important of the available strategies for preventing disease induced by chemicals in the environment. PMID- 2600205 TI - In vitro determination of IgE antibodies in the diagnosis of atopic allergy. AB - The reaction of IgE antibodies is important in asthma and hay fever. Their role in skin diseases is more obscure and needs to be studied further. IgE antibodies play a role in contact urticaria and a more doubtful role in the triggering of atopic dermatitis. A well-standardized radioallergosorbent test is a valuable tool in the diagnosis of these diseases. A new test for the detection of atopy is discussed. PMID- 2600206 TI - Current concepts in clinical dermatologic allergy testing. Proceedings of a symposium. Uppsala, Sweden, August 18-20, 1988. PMID- 2600207 TI - Patch testing technique. AB - The patch test is a necessary tool to evaluate contact dermatitis and other pruritic dermatoses. To obtain accurate test results, however, high-quality test material must be used, the application technique must be correct, and the results must be evaluated with skill and criticism. The relevance of the test should be related to the patient's history: both positive and negative test results are of importance. PMID- 2600208 TI - Aspects of pharmaceutical and chemical standardization of patch test materials. AB - The choice of vehicle for patch test materials is important for the bioavailability and stability of the allergens. Examples are given from the standardization of the TRUE Test and include caine mix, Kathon CG, and fragrance mix. PMID- 2600209 TI - Proallergens of formaldehyde applied in patch testing of formaldehyde contact allergy. AB - The ability of the nonliquid, nonvolatile proallergen of formaldehyde, N hydroxymethylsuccinimide, to test for contact allergy to formaldehyde has been investigated by in vitro penetration studies in human epidermis. Compared with the standard test, 1% formaldehyde in water, N-hydroxymethylsuccinimide equal to 0.8 mg formaldehyde gave a similar penetration profile. This is explained by cleavage of N-hydroxymethylsuccinimide into formaldehyde and carrier (succinimide) by transepidermal water on the surface of the skin. Results were confirmed by a guinea pig maximazation test on animals sensitized to formaldehyde and in a preliminary clinical study on nine patients with known allergy to formaldehyde. PMID- 2600210 TI - Preliminary studies of the TRUE test patch test system in the United States. TRUE Test Study Group. AB - Comparison of the TRUE Test patch test system with the chamber system recommended by the North American Contact Dermatitis Group showed concordance of results in 98% of tests with nickel, epoxy resin, and ethylenediamine dihydrochloride. Also, a panel of 12 TRUE Test screening allergens tested on 128 patients showed no irritant reactions but did show 46 positive responses of varying intensity. The TRUE Test is a promising alternative to current methods and offers the advantages of easy application and factory quality control. PMID- 2600211 TI - Reproducibility of patch test results: comparison of TRUE Test and Finn Chamber test results. AB - To evaluate the reproducibility of patch test results, duplicate patch test series comprising 12 allergens were simultaneously applied to either side of the back in 63 patients by the use of a newly developed patch test system, TRUE Test. When a positive test result occurred on only one side of the back, it was regarded as nonreproducible. For evaluation of the concordance of test reactions between the TRUE Test and the Finn Chamber test, the same 12 allergens mixed in petrolatum were also applied to the upper back according to the Finn Chamber technique. The reproducibility of TRUE Test results was compared with the reproducibility of the Finn Chamber test in 76 other patients. The concordance of positive reactions between the two tests was 57%, somewhat lower than in recently published studies. The percentage of nonreproducible positive results was more than twice as high with Finn Chambers, (22 of 58 positive reactions, or 37.9%) as with the TRUE Test (5 of 28 reactions, or 17.9%). However, this difference in reproducibility in the two test systems was not significant as determined by the chi 2 test (p less than 0.05). PMID- 2600212 TI - Patch testing in atopic dermatitis. AB - Because patients with atopic dermatitis are less prone to type IV allergies, there has been controversy regarding the role of patch testing in these patients. However, recent observations indicate that patch testing with standard allergens often adds valuable information about contact sensitivity in these patients. PMID- 2600213 TI - Aeroallergen contact can exacerbate atopic dermatitis: patch tests as a diagnostic tool. AB - Previous studies have documented that atopic dermatitis can worsen when patients ingest specific foods to which they are sensitive. In this article we demonstrate that patient contact with specific aeroallergens can cause flares of atopic dermatitis. Marked improvement in skin symptoms was noted when 12 patients (eight males and four females; ages, 1 to 54 years) were removed from their unusual environment. In response to prick tests, these patient had markedly positive, immediate wheel-and-flare reactions to a variety of aeroallergen extracts (tree, grass, and weed pollen; house dust mite; animal protein; and mold spores). The same patients were subsequently patch tested on uninvolved, nonabraded skin with the allergen extracts that had yielded positive prick tests. Patch tests were applied for 48 hours, removed, and interpreted 24 hours later. The patients reacted to specific aeroallergens with an eczematous eruption at 48 and 72 hours. Positive delayed cutaneous reactions correlated strongly with aeroallergens identified in the patient's environment or suspected by the patients as provocateurs of their atopic dermatitis. Delayed cutaneous reactions were negative to allergens not historically relevant. Continued avoidance of aeroallergens that elicited an eczematous reaction at patch test sites resulted in marked improvement or resolution of dermatitis in all patients. We conclude that aeroallergen contact plays an important role in select patients with atopic dermatitis. PMID- 2600214 TI - Contact urticaria and anaphylaxis to latex. AB - Contact urticaria and anaphylaxis to latex is reported in two patients. One case was associated with oral and vaginal exposure to a condom and the other with rectal exposure to a latex glove. Both patients had positive reactions to scratch or prick tests to pieces of latex, as well as latex radioallergosorbent test (RAST). The diagnosis of contact urticaria to latex is difficult to make on the basis of history alone. PMID- 2600215 TI - The compilation of patch test information by the use of computerized data bases. AB - The use of computer technology to store, retrieve, and analyze patient data is not new. This article reviews the use of computerized data bases in patch test result record keeping. Efforts of the North American Contact Dermatitis Group serve as an example of how to create, manage, and apply these data. PMID- 2600216 TI - Challenges for the future of patch testing. PMID- 2600217 TI - Growth kinetics of Streptococcus thermophilus at subbacteriostatic penicillin G concentrations. AB - Streptococcus thermophilus may be subjected to the effects of penicillin G in contaminated milk used for yogurt production. Sensitivity of this microorganism to penicillin G has been conventionally determined by the help of penicillin G impregnated disks placed on solid media. It was observed that the bacteriostatic penicillin G concentration was much greater in liquid media than in solid media. The conventional disk method may not be appropriate for antibiotic sensitivity determinations if the microorganisms will be used in liquid culture. A simple mathematical model simulated the growth of S. thermophilus in liquid culture. Numerical values of this model's parameters were regarded as the measure of the antibiotic effect on the culture. In penicillin G containing fresh medium, small concentrations of antibiotic decreased the specific growth rate considerably. Increasing the antibiotic concentration caused only slight additional decline. Antibiotic shock, i.e., rapidly introducing penicillin G into an actively growing antibiotic-free culture, stopped growth of the penicillin G-resistant microorganisms, and no death was observed, but a fraction of the microorganisms were killed in the wild culture. Both the wild and the resistant cultures recovered from the shock in a few hours. Addition of penicillin G-resistant microorganisms together with the antibiotic dosage into the wild culture prevented death. PMID- 2600218 TI - Subcellular and ultrastructural localization of alkaline phosphatase in lactating rat mammary glands. AB - The subcellular fractions of lactating rat mammary glands were isolated by differential centrifugation. The mean specific activity of alkaline phosphatase in various fractions was in order greatest to least: microsomes, Golgi, mitochondria, nuclei, and cytosol. Alkaline phosphatase was examined cytochemically by transmission electron microscopy. Alkaline phosphatase activity was localized on myoepithelial membranes, basal and possibly lateral membranes of secretory epithelial cells, and endothelial cells. This finding agreed with biochemical data associating this enzyme activity with microsomes. However, intracellular activities could not be detected on Golgi, secretory vesicles, or apical plasma membranes. Saponin uncovered the activity in that portion of the endoplasmic reticulum of secretory cells adjacent to myoepithelial cells. The identify of this enzyme was further confirmed by selective inhibition studies using dithiothreitol and levamisole. Alkaline phosphatase activities were detected biochemically in lipid droplet "membranes" of secretory epithelium and fat globule membranes. Activity decreased with increasing globule size, indicating that milk alkaline phosphatase originates from lipid droplets of secretory epithelium. The predominance of alkaline phosphatase activity in myoepithelial cell plasma membranes suggests that this enzyme could be involved in cell surface reactions related to oxytocin-mediated milk ejection. In secretory epithelium, it was associated with basal and possibly lateral membranes and lipid droplets that lead to the secretion of milk fat. PMID- 2600219 TI - Nutritional implications of somatotropin for lactating cows. AB - Milk yield, feed intake, physiology, health, and reproduction of cows supplemented with somatotropin are like those of genetically superior cows. Lactation curves are shifted upward and are more persistent. Holsteins, Jerseys, Brown Swiss, and Ayrshires respond. In most cases, responses in primiparous and multiparous animals are similar. Milk composition, ration digestibility, maintenance requirements, and the partial efficiency of lactation are not affected by somatotropin. More nutrients are directed to milk synthesis. Initially, body stores of fat, protein, and glycogen provide these nutrients, but after a few weeks, feed intake increases. Cows supplemented with somatotropin should be fed like high producing cows. When ration energy density is increased by feeding grain, buffers such as sodium bicarbonate should be included to prevent alterations of hydrogen balance in the rumen and tissues. Ration energy density can also be increased with ruminally inert fat like calcium salts of fatty acids. Rations should be balanced for rumen degradable and undegradable protein. Rations for high milk yields are expensive, but income over feed costs are greater. Cows should be moved to rations with lower nutrient densities on the basis of body condition and milk yield. Current feeding recommendations can be used for cows supplemented with somatotropin. PMID- 2600220 TI - Parturient hypocalcemia in jersey cows fed alfalfa haylage-based diets with different cation to anion ratios. AB - Jersey cows were fed three alfalfa haylage-based diets with different cation anion balances beginning 6 wk preceding third or later calving and ending 24 to 36 h postpartum. Sodium and Cl as percentages of dietary DM were .08 and 1.66 in diet 1 (anionic, 5 cows), .44 and .91 in diet 2 (intermediate, 6 cows), and 1.60 and .34 in diet 3 (cationic, 6 cows). Cation-anion balances were 22, 60, and 126 meq/100 g DM; Ca:P ratios averaged 4:1. Cows fed diet 1 in comparison with cows fed diets 2 or 3 over 6 wk had similar concentrations of Ca, P, and Na but higher concentrations of Mg and K in plasma and higher urinary excretions of Ca and Mg. Concentrations of 1,25-dihydroxyvitamin D 3 d before parturition were higher in cows fed diet 1 than in cows fed diets 2 or 3. Within 36 h after calving, mean concentrations of Ca in plasma (mg/dl, range) of cows fed diets 1 to 3, respectively, were 7 (8.7 to 6.2), 6.5 (7.8 to 3.9), and 6.3 (7.8 to 3.8). Number of cases of clinical milk fever by diet were 0 of 5, 2 of 6, and 1 of 6 cows. Alteration of dietary cation-anion balance by addition of Cl may effectively reduce incidence and severity of parturient hypocalcemia. PMID- 2600221 TI - Prediction of duodenal nitrogen supply from degradation or organic and nitrogenous matter in situ. AB - The contribution of different feedstuffs to nitrogen reaching the duodenum was evaluated in situ. Dacron bags containing barley grain, corn grain, wheat silage, corn silage, alfalfa hay, rye grass, whole cottonseeds, or soybean meal were suspended in the rumens of three dairy cows fed roughage and concentrate diets. The effective degradability of the nitrogenous and organic matter of feedstuffs was calculated from their residues after incubation in the rumen for 3, 6, 9, 12, 24, 36, or 48 h. The duodenal nitrogen content at ruminal outflows of 2, 5, or 8%/h was calculated as the sum of undegradable dietary nitrogen and potential microbial nitrogen (assuming 32 g N/kg ruminally degradable organic matter). Comparison of the in situ estimates with previously reported in vivo measurements of duodenal nitrogen in cattle fed diets with similar ingredients to the tested feedstuffs yielded a linear relationship (r2 = .887). The dacron bag technique appears to hold promise for the prediction of nitrogen flow to the duodenum. PMID- 2600222 TI - Metabolism of peptides and amino acids during in vitro protein degradation by mixed rumen organisms. AB - In vitro inoculum enriched with particle-associated organisms was prepared using rumen contents from a cow fed a 60% forage, 40% concentrate diet. Treatment of in vitro inoculum with cetyltrimethylammonium bromide was used to release intracellular free amino acids from mixed rumen organisms. Addition of 10 mM tosylarginine methyl ester, a competitive inhibitor of trypsin, decreased degradation rate and intracellular free amino acids in incubations containing either casein or serum albumin. Extracellular peptides increased rapidly to a maximum at 60 min in casein incubations but were not different from zero in albumin incubations. Accumulation of intracellular free amino acids was maximal at 60 min in casein and albumin incubations; the concentration observed with albumin was about one-fourth that with casein. Ammonia production from intact casein was slightly greater than that from acid and enzymatically hydrolyzed casein and about 80% greater than that from albumin. Ammonia production and appearance of extracellular free amino acids lagged behind accumulation of intracellular free amino acids. Results suggest that formation and metabolism of extracellular peptides are important in controlling the rate of protein degradation by mixed rumen organisms. PMID- 2600223 TI - Recovery of fecal chromium used as a digestibility marker in cattle. AB - Chromium content of fecal samples that were mixed with Cr-mordanted rumen contents at 5 or 10 g/200 g feces in Experiment 1 and at 5 or 10 g/300 and 200 g feces in Experiment 2 was determined by atomic absorption spectroscopy. Recovery of Cr was estimated after digesting fecal samples, which were frozen fresh and later thawed or dried in either a forced draft oven at 60 degrees C or in a microwave oven in Experiment 1. Experiment 2 evaluated the efficacy of each of three methods of digestion in recovery of Cr from fecal samples. Recoveries of Cr from feces were calculated relative to the Cr content of the Cr-mordanted rumen contents, which were determined by atomic absorption spectroscopy of samples digested with concentrated nitric acid in the presence or absence of the wetting agent Tween 80. Recovery of Cr from fecal samples frozen fresh and later thawed was greater than that from either forced draft oven or from microwave oven-dried samples, especially when the concentrated nitric acid digestion was used. Neither the double ashing procedure nor the digestion with the weaker nitric acid did not improve Cr recoveries from the samples. PMID- 2600224 TI - Influence of dietary protein concentration and degradability on performance of lactating cows during hot environmental temperatures. AB - To test effects of protein concentrations and degradability, 60 lactating Holstein cows in midlactation were offered the following diets during three trials between May and October in Tucson, AZ: high protein (18.4%), high degradability; high protein (18.5%), medium degradability; medium protein (16.1%), high degradability; and medium protein (16.1%), medium degradability. Diets comprised 39% alfalfa hay, 12% cottonseed hulls, 10% whole cottonseed, and 39% concentrate (DM) and concentrates contained 60, 40, 57, and 40% degradability, respectively, as determined by ficin assay. Rectal and ambient temperatures suggested that cows were under moderate to intense heat stress, as did group water intakes, which were increased about 15% by high degradability. Milk yields (3.5% FCM) and persistencies were lower for the high protein, high degradability diet than for all others. Mean DM intakes across treatments were quite high but were lower on high than medium protein; whereas ruminal ammonia and blood serum urea were higher on high protein. Milk composition, ruminal VFA, serum glucose, thyroxine, triiodothyronine, and cortisol were not affected by treatment. PMID- 2600225 TI - Influence of excess dietary copper on lipid composition of calf tissues. AB - Lipid composition of calf liver, heart, and skeletal muscle was measured, as affected by control Cu (10 ppm in DM), high Cu (1000 ppm), or high Cu plus high Zn (1000 ppm) in milk replacer. High dietary Cu increased all lipid classes in liver, some in the heart, and decreased all lipid classes except cholesterol in muscle. Zinc inhibited many of the changes in tissue lipid classes by excess copper. High Cu intake increased fatty acid unsaturation (palmitoleic, oleic, linoleic acids) and decreased stearic acid in phosphatidylcholine and phosphatidylethanolamine of liver and heart. Excess Cu tended to have an opposite effect in changing fatty acid concentrations in liver and muscle. Activities of various desaturases and elongases were estimated in liver, heart, and muscle using ratios of fatty acid precursors to products in combined phosphatidylcholine and phosphatidylethanolamine. High Cu intake frequently altered activities of these enzymes in all three tissues with additional high Zn usually coregulating activity in the direction opposite to Cu. PMID- 2600226 TI - Models for genetic analysis of dystocia and calf mortality. AB - Calvings of 106,750 Israeli Holstein heifers were analyzed for dystocia and calf mortality, which were scored dichotomously. Models fitted included herd-year season, sex of calf, calving age, calving month, sire of cow, sire of calf, and groups of sire of cow and calf. Herd-year-season, sire of cow and of calf, and residuals were random with diagonal variance-covariance matrices. Traits were analyzed with and without a herd-year-season effect, and dystocia was analyzed separately for male and female calvings and with both sexes combined. Variance components were estimated by REML for linear models and by the counterpart of REML for threshold models. Heritability estimates were two to four times larger in threshold than in linear models, but correlations between corresponding sire evaluations were all greater than .9. Correlations between evaluations computed with and without herd-year-season effects were .9 for sire of calf evaluations for dystocia and greater than .97 for all other evaluations. Correlations between sire evaluations computed separately for male and female calvings were between .3 and .7. Thus, calving difficulty is expressed differently in male and female calvings. Genetic trends were unfavorable for dystocia but favorable for calf mortality. Phenotypic trends were curvilinear with maxima in 1982 and 1983 for calf mortality and dystocia. PMID- 2600227 TI - Genetic analysis of fertility traits in Israeli dairy cattle. AB - First through third parity lactation records of 91,770 Israeli Holsteins inseminated between 1980 and 1986 were evaluated by univariate mixed model methodology for fertility and production traits. The analytical model included the effects of herd-year-season, group of sires, sire, cow, and residual. Sire, cow, and residual were random: all other effects were fixed. Sires were assumed to be unrelated. Variance components were computed separately for first and second parity by Henderson's method 3. First parity heritabilities were .035 for conception status [1/number of inseminations to conception], .048 for days from calving to first breeding, and .135 for milk production. Corresponding second parity heritabilities were .022, .031, and .125. First parity genetic correlations were -.02 between conception status and milk, .27 between days to first breeding and milk, and -.03 between the two fertility traits. All environmental correlations, and all second parity genetic correlations among these traits, were between -.2 and .2. Genetic trends, estimated as twice the regression of the evaluation of the cow's sire on calving date, were 1% for conception status, .1 for days to first breeding, and 154 kg milk/yr. Thus, there was no indication of an adverse genetic relationship between fertility and milk production in this population. PMID- 2600228 TI - Heifer fertility and its relationship with cow fertility and production traits in Holstein dairy cattle. AB - Breeding receipts from three AI units were merged with Ontario Dairy Herd Improvement Corporation and Record of Performance production records. Data comprised 53,705 heifer, 41,253 lactation 1, 14,688 lactation 2, and 3054 lactation 3 records by daughters of 2150 sires represented in 15,877 herd-year seasons of birth. Three measures of heifer fertility, three measures of cow fertility, and three measures of production were investigated. Measures of heifer fertility were ages at first and last breeding and number of inseminations per conception. Cow fertility traits were days from calving to first breeding, days open, and number of inseminations per conception. Production traits were breed class average milk, breed class average fat, and fat percentage. Relationships among these nine traits for the first three lactations were estimated using a maximum likelihood multiple-trait procedure. The linear mixed model for each trait included fixed effects of herd-year-season of birth and genetic groups of sire and the random effect of sire. Transformations of the data for nonnormality had no influence on the estimates of genetic and phenotypic parameters. The heritability of .12 for age at first insemination, which was higher than other heifer fertility traits, indicated that selection would result in genetic response. Genetic and phenotypic correlations between heifer fertility and cow fertility and production traits in all three lactations were not different from zero. There was no genetic antagonism between fertility and subsequent production traits. PMID- 2600229 TI - Relationships between fertility and production in Holstein dairy cattle in different lactations. AB - Record of Performance and Dairy Herd Improvement Corporation production records of Ontario Holstein cows were merged with breeding receipts of three Ontario AI units from September 1981 through December 1985. Relationships between fertility and production in the first three lactations were investigated for 97,368 daughters of 3806 sires in 22,768 herd-hear-seasons of calving. Fertility traits were days from calving to first insemination, number of inseminations per conception, and days open. Production traits were age and month of calving adjusted 305-d milk and fat yields and fat percentage. Multiple-trait maximum likelihood was used to estimate variances and covariances. Heritabilities for the first three lactations were .18, .18, and .19 for milk yield; .20, .19, and .19 for fat yield; and .58, .52, and .48 for fat percentage. Heritabilities of fertility traits ranged from .03 to .06. Genetic and phenotypic correlations between fertility and production traits in all three lactations were essentially 0. Genetic correlations between different lactation production traits ranged from .2 to .65. Repeatabilities of fertility traits ranged from .05 to .16 in different lactations. Repeatabilities for production traits in different lactations ranged from .51 to .77. Genetic and phenotypic correlations between fertility and production in the subsequent lactation and between production and subsequent lactation fertility were also very low or zero. PMID- 2600230 TI - Relationship of bull fertility with daughter fertility and production traits in Holstein dairy cattle. AB - The phenotypic and genetic correlations between fertility ratings of AI bulls for conception rate and their estimated breeding values for daughters' fertility and production traits were calculated. Genetic correlations between fertility ratings of bulls for conception and heifer fertility traits (age at first breeding, age at last breeding, and number of insemination per conception) were negative and ranged from -.04 to -.23, indicating daughters of bulls with high fertility ratings were younger at first breeding and required fewer services to conceive. In general, genetic correlations between fertility ratings of bulls for conception rate and cow fertility traits (days from calving to first breeding, days open, and number of inseminations per conception) and production traits (breed class average milk and fat and fat percentage) in the first two lactations were also moderate to high and in the favorable direction. Although heritability of both male and female fertility is low, these data indicate that heavy use of sires with high fertility ratings could have a mild positive effect on both male and female fertility. Evidence is also found to indicate that in this breed, selection for increased milk yield should not impair genetic ability of cows to reproduce. PMID- 2600231 TI - Induction of bovine sperm capacitation by TEST-yolk semen extender. AB - Ejaculated bull semen was diluted 1:10 in the TEST-yolk buffer, cooled slowly to 4 degrees C, and stored for up to 48 h. Aliquots were taken at 0, 4, 8, 16, 24, and 48 h and washed once or three times in bovine serum albumin-saline and the sperm pellets resuspended in this saline. Fertilization of zona-free hamster oocytes was used to assess sperm capacitation. Motility differed between samples washed once or three times (53.7 vs. 21.7%). Motility was highest at 4 h storage but did not differ between 16, 24, or 48 h of storage. More sperm without intact acrosomes were found at 4 h than at 0 h, but the percentage did not change further until after 24 h. Penetration of oocytes was not different between sperm washed once or three times (28.5 vs. 26.9%). No penetration occurred at 0 h, and highest penetration rates occurred at 4 and 8 h of storage (32.1 and 33.4%). Penetration rates at 16, 24, and 48 h were not different (25.3, 25.2, 22.5%). In conclusion, storage of bull sperm in TEST-yolk buffer for 4 to 48 h resulted in capacitation. Even though capacitation was induced by 4 h, at least 71% of the sperm population had not undergone an acrosome reaction by 48 h of storage. This may explain why penetrability was maintained over this period. PMID- 2600232 TI - Effect of washing and capacitating media pH on bull sperm motility, acrosome integrity, and ability to penetrate zona-free hamster oocytes. AB - Bovine-ejaculated sperm were washed thrice in bovine serum albumin-saline media, pH 7.2 to 8.4, and incubated at 37 degrees C in Ca++-free Tyrode's media. pH 7.2 to 8.4, for 0, 2, 4, 6, and 8 h. Motility was highest when sperm were washed in pH 7.2 medium and incubated in pH 8.0 or 8.4 media. Motility remained above 50% until 8 h. Washing in pH 7.6, 8.0, or 8.4 media induced more acrosome reactions after incubation than washing at pH 7.2. Percentage of acrosome-reacted sperm increased at each successive time period. Sperm penetrated more oocytes at 4, 6, and 8 h when wash medium pH was fixed at 7.2 and capacitating media pH was raised at .4 unit increments from 7.2 to 8.4. When sperm were washed in pH 7.2 medium, the postincubation penetration rates peaked at 8 h. With wash media of pH 7.6, 8.0, or 8.4, the postincubation penetration rates peaked at 4 h and then gradually declined. In conclusion, the most effective system for capacitating bull sperm was a pH 7.6 wash followed by capacitation in pH 7.6 medium for 4 to 8 h and this system resulted in the highest penetration rates. Wash media pH hastened capacitation but was not a capacitating agent. PMID- 2600233 TI - Identification of the capacitating agent for bovine sperm in egg yolk-TEST semen extender. AB - Bovine sperm can be capacitated in egg yolk-TEST buffer. To determine what constituent of the buffer was responsible, ejaculated semen was diluted 1:10 at 37 degrees C with the following 20% egg yolk (vol/vol)-containing buffers: TES Tris, TES-tetramethylammonium hydroxide, taurine-Tris, citric acid-Tris, citrate, egg yolk salts, egg yolk proteins Tris, and citrate-taurine. Buffers were pH 7.6 and 321 to 325 mOsmol/kg. Extended semen was cooled slowly to 4 degrees C and stored 8 h. Sperm taken at 0 and 8 h were washed in pH 7.6 bovine serum albumin saline and assessed for motility and capacitation using zona-free hamster eggs. Sperm motilities at 0 and 8 h were similar (60 to 73%) in all extenders except citric acid-Tris (54%) and egg yolk proteins Tris (15%). Bull sperm, stored 8 h in egg yolk-TEST, became capacitated. Because sperm storage in egg yolk-citrate did not result in penetration, both egg yolk and citrate were ruled out as capacitating agents. Capacitating activity resided in the TES and Tris molecules. The TES molecule contains a Tris component and this capacitated bull sperm. The TES molecule also contains a taurine component. However, taurine was not a capacitating agent for bull sperm. In conclusion, both TES- and Tris-containing buffers, alone or together (TEST), were equally effective in capacitating bull sperm. PMID- 2600234 TI - Relationship among climatological variables and hourly distribution of calvings in Holsteins fed during the late afternoon. AB - A survey of 924 calvings of Holstein cows and heifers in one large commercial herd during the fall of 1985 revealed a nonuniform pattern of calving over a 24-h period. Pregnant females were attended 24 h/d and fed daily a complete diet between 1500 and 1600 h during the dry period or the last 30 to 60 d of gestation. More calvings occurred from 0601 to 1800 h than from 1801 to 0600 h (56 versus 44%). Cows calving during the last 12 h of the day (1201 to 2400 h) had gestation periods that averaged 1.3 d longer than cows calving during the first 6 h of the day. Length of gestation was increased 1.3 d for every hour decrease in daylength from September to December but was unaffected by any other climatological measure (barometric pressure, precipitation, wind velocity, temperature, percentage sunshine, or relative humidity). The hour of calving was unrelated to any of the climatological measures during the week preceding parturition. However, partial regressions of climatological variables on days to calving revealed significant regressions for barometric pressure [quadratic; beta = (60.1 +/- 2.6) x 10(-13) mm2 Hg/d], precipitation [beta = (2.02 +/- .8) x 10( 1) mm/d], humidity [beta = (1.2 +/- .2) x 10(-2)%/d]. and daylength [beta = (-3.5 +/- .5) x 10(-1) h/d]. It was concluded that pregnant cows and heifers fed during the late afternoon calved in a nonrandom pattern during the 24-h day; more calvings occurred during daylight hours. Changes in various environmental measures may serve as biological cues to initiate parturition in the bovine. PMID- 2600235 TI - Effect of the combination of monensin and isoacids on rumen fermentation in vitro. AB - Effects of isoacids, monensin, or a combination of them on fermentation by mixed rumen bacteria were investigated using a continuous culture technique. The culture was allowed to stabilize for 4 d before treatments were imposed. Comparisons between treatments were made on d 11 and 12 of the culture. Isoacids (equal proportions of isobutyric, 2-M-butyric, isovaleric, and valeric acids) at 15 mg/dl of culture media increased acetate (6.17 vs. 5.48 meq/dl) and total VFA production (8.93 vs. 7.87 meq/dl) compared with that of controls. Monensin at 150 micrograms/dl reduced acetate (3.74 vs. 6.02 meq/dl) and VFA (6.84 vs. 8.54 meq/dl) but increased propionate (2.28 vs. 1.74 meq/dl) relative to control. The combination of isoacids and monensin increased acetate relative to monensin alone (5.24 vs. 3.74 meq/dl) but did not alter the effect of monensin on propionate concentration (2.32 vs. 2.28 meq/dl). It is concluded that monensin decreases acetate production by 35% and when isoacids are added to the cultures containing monensin, acetate production is restored. PMID- 2600236 TI - In vitro degradation of choline from selected feedstuffs and choline supplements. AB - The objective of this experiment was to determine the extent of in vitro degradation of choline from barley, corn, corn gluten meal, cottonseed meal, fish meal, soybean meal, alfalfa hay, timothy hay, choline chloride, and choline stearate. During four individual fermentation runs, samples were incubated in vitro for .25, 1, 3, 6, 12, 18, 24, 36, and 48 h with an inoculum mixture containing rumen fluid obtained from a rumen-fistulated dairy cow fed 17.5% corn silage and 28.7% grass silage and 53.8% concentrate diet. Because of their low choline content (less than .68 mg/g) corn, corn gluten meal, alfalfa hay, and timothy hay gave erratic values for choline disappearance for different fermentation runs and times of incubation although disappearance tended to increase with time. Data for the rest of the feeds and choline supplements were analyzed using nonlinear regression procedure to obtain estimates of potentially degradable choline, rapidly degradable choline, and the rate of choline degradation in vitro. The mean estimates of rumen degradable choline (%) were 79.4, 84.7, 82.9, 83.8, 98.0, and 98.6 for barley, cottonseed meal, fish meal, soybean meal, choline stearate, and choline chloride, respectively. The results suggest that incorporating choline-rich feedstuffs in diets can only marginally increase the postruminal flow of choline in dairy cows. PMID- 2600237 TI - Altering milk composition through genetic selection. AB - The genetic relationships among carrier, fat, protein, and lactose will allow genetic alteration in any direction desired, although some changes would be much easier than others. Genetic parameters may vary somewhat between different populations, thus affecting the rates of different directions of change. In general, however, selection for an alteration in the fat:protein ratio would proceed rapidly, principally through alteration of fat concentration. Genetic alteration of composition is likely only if economic incentives for such change exist. Economic values, and therefore selection pressure, should be applied to amounts of components rather than concentrations. Recent developments in the theory of deriving economic weights for animal breeding indicate that selection indexes need to be reassessed. Although optimum breeding goals will vary somewhat, in most circumstances fat and protein yields and concentrations and the fat:protein ratio are likely to increase due to genetic selection. Only in the unlikely situation that fat has a very small or negative economic weight are other changes indicated. Lactose concentrations are unlikely to change much in any situation. Genetic variation in the composition of fat and protein, while of biological interest, is unlikely to be of more than minor importance in genetic improvement. PMID- 2600238 TI - Controlled prospective longitudinal study of women with cancer: I. Sexual functioning outcomes. AB - The incidence and etiology of sexual difficulties for women with survivable cancer were studied. Women with early stage gynecologic cancer (n = 47) were assessed after their diagnosis but prior to treatment and then reassessed at 4, 8, and 12 months posttreatment. Sexual and medical outcomes were compared with data from members of two matched comparison groups who were also assessed longitudinally: women diagnosed and treated for benign gynecologic disease (n = 18) and gynecologically healthy women (n = 57). Global sexual behavior disruption did not occur, but the frequency of intercourse declined for women treated for disease, whether malignant or benign. In relation to the sexual response cycle, diminution of sexual excitement is pronounced for women with disease; however, this difficulty is more severe and distressing for women with cancer, possibly due to significant coital and postcoital pain, premature menopause, treatment side effects, or a combination. Changes in desire, orgasm, and resolution phases of the sexual response cycle may also occur, but they are of lesser magnitude or duration or both. Approximately 30% of the women treated for cancer were diagnosed with a sexual dysfunction. The nature, early timing, and maintenance of sexual functioning morbidity suggest the instrumental role that cancer and cancer treatments play in these deficits (particularly arousal problems) and suggest that preventive therapies are necessary. PMID- 2600239 TI - Controlled prospective longitudinal study of women with cancer: II. Psychological outcomes. AB - The incidence and etiology of major life difficulties for women with survivable cancer were studied. Women with early stage cancer (n = 65) were assessed after their diagnosis but prior to treatment and then reassessed at 4, 8, and 12 months posttreatment. Two matched comparison groups, women diagnosed and treated for benign disease (n = 22) and healthy women (n = 60), were also assessed longitudinally. Results for four life areas are reported: (a) The emotional response to the life-threatening diagnosis and anticipation of treatment was characterized by depressed, anxious, and confused moods, whereas the response for women with benign disease was anxious only. In both cases, these responses were transitory and resolved posttreatment. (b) There was no evidence for a higher incidence of relationship dissolution of poorer marital adjustment; however, 30% of the women treated for disease reported that their sexual partners may have had some difficulty in reaching orgasm (i.e., delayed ejaculation) after the subjects' treatment. (c) There was no evidence for impaired social adjustment. (d) Women treated for cancer retained their employment and their occupations; however, their involvement (e.g., hours worked per week) was significantly reduced during recovery. These data and those in a companion report (Andersen, Anderson, & deProsse, 1989) suggest "islands" of significant life disruption following cancer; however, these difficulties do not appear to portend global adjustment vulnerability. PMID- 2600240 TI - Pretest expectancies and cognitive impairment in alcoholics. AB - Alcoholics' neurological deficits have been attributed to cognitive impairment associated with brain dysfunction. Because alcoholics perceive themselves as impaired in higher cognitive functions, we investigated the alternative hypothesis that their deficits are predicted by lowered expectancies for successful performance. Ss were 48 male, middle-aged Veterans Administration inpatient alcoholics and 36 community controls. Subjects completed a standard series of neuropsychological tests. Before taking each test, Ss were asked how well they expected to do on that test in relation to members of their community. As predicted, means for the overall measures of expectancies and performance were significantly lower for alcoholics than for control Ss. Although expectancies were significantly correlated with performance, regression analyses indicated they could not account for the obtained performance differences. PMID- 2600241 TI - The role of early aggressive behavior in the frequency, seriousness, and types of later crime. AB - This study reports on the relation between aggressive behavior at early school age and later delinquent activities of 1,027 subjects (517 boys and 510 girls) prospectively followed from late childhood to adulthood. The research group was a fairly unbiased age sample of children, covering most of the range of social and psychological upbringing conditions for 10-year-old children in a Swedish community. Aggressiveness was measured by teacher ratings at ages 10 and 13 years. Delinquency, defined as registered lawbreaking, was covered through age 26. There was a strong connection between both the aggressiveness ratings at ages 10 and 13 and adult delinquency for boys, with the majority of delinquents and recidivists being recruited from the early-aggressive boys. High ratings of aggressiveness were characteristic of boys who later committed violent crimes and damage to public property and generally of subjects with a diversified offense pattern. Aggressiveness was not predictive of later crime for girls until they reached the age of 13. For both sexes the relation between aggressiveness and crime was to a large extent independent of intelligence and family education. The possibility of making individual prognoses and the role of aggressiveness for the sexes are discussed. PMID- 2600242 TI - A prospective replication of the protective effects of IQ in subjects at high risk for juvenile delinquency. AB - The purpose of the study was to test the replicability of a protective effect of high IQ against criminality. Support has been found in prior studies for the hypotheses that Ss at high risk would have an elevated risk of serious criminal involvement, that seriously criminal Ss would have a lower mean IQ score than noncriminal Ss, and that Ss at high risk who had not become involved in serious criminal behavior would have the highest IQs. This report tests these hypotheses in a prospective design. Subjects were 1,037 members of a longitudinal investigation of a New Zealand birth cohort. IQs were examined for male and female Ss who were divided into 4 groups formed on the basis of risk status at age 5 years and delinquency outcome at ages 13 and 15. Analyses were conducted with and without mild delinquents excluded from the nondelinquent groups. We found that male and female delinquents showed significantly lower IQ scores than nondelinquents. By varying S selection procedures, we also found that a very high IQ may help boys, even those at risk, to stay free of delinquency altogether. PMID- 2600243 TI - Sickle cell disease pain: relation of coping strategies to adjustment. AB - This study examines pain coping strategies in a relatively neglected pain population, sickle cell disease (SCD) patients. Seventy-nine patients diagnosed with SCD were given a structured interview to assess pain, activity level, and health care use during painful episodes. Patients also completed the SCL-90-R as an index of psychological distress and the Coping Strategies Questionnaire. Regression analyses controlled for age, sex, and disease severity measures. Results indicated that the coping strategies factors were important predictors of pain and adjustment. Individuals high on Negative Thinking and Passive Adherence had more severe pain, were less active and more distressed, and used more health care services. Individuals high on Coping Attempts were more active during painful episodes. PMID- 2600244 TI - Risk factors for emotional/behavioral problems in young adolescents: a prospective analysis of adolescent and parental stress and symptoms. AB - Stressful events in the lives of 309 10- to 15-year-olds and stressful events and psychological symptoms reported by their parents were examined in a 9-month study. Ss' self-reported emotional/behavioral problems were predicted by their reports of stressful events and their fathers' reports of psychological symptoms in cross-sectional analyses. Analyses at follow-up after controlling for initial reports of emotional/behavioral problems and prospective analyses predicting from first assessment to follow-up yielded significant effects for Ss' self-reported stressful events. Mothers' reports of children's problems were predicted by mothers' psychological symptoms in cross-sectional analyses and at follow-up after controlling for initial emotional/behavioral problems. Only prior levels of maternal reports of emotional/behavioral problems predicted mothers' reports of their children's problems 9 months later. PMID- 2600245 TI - Assessing the effects of clinic-based psychotherapy with children and adolescents. AB - Recent meta-analyses suggest that psychotherapy is quite effective with children and adolescents. However, most research in those analyses involved controlled laboratory interventions that may not represent typical therapy in clinics. We studied more representative treatment as it routinely occurs, in 9 clinics. We compared 93 youngsters who completed a course of therapy with 60 who dropped out after intake. At intake, the groups did not differ on demographic, family, or clinical measures, including Child Behavior Checklist (CBCL) scores. Six months later (when therapy had ended for 98% of the treated children) and again 1 year later, the 2 groups were compared on CBCL scores, parent ratings of each child's major referral problem, and (for a subsample) teacher reports. No comparison showed significant main effects of therapy. The findings (a) raise questions about the generalizability of findings from research-oriented therapy and (b) suggest that the control and precision of research therapy may be needed in clinical practice. PMID- 2600246 TI - Short-term structured treatment for avoidant personality disorder. AB - Forty-two men and 34 women (mean age 27.5 years) who met DSM-III criteria for avoidant personality disorder were randomly assigned to 1 of 3 treatment conditions or to a waiting-list control group. Treatment Ss who participated in a 10-week group treatment program displayed significantly greater improvement on a variety of self-report and behavioral measures than did untreated control subjects. The inclusion of skills-training procedures did not contribute to the effects of graduated exposure procedures alone. The gains made during treatment were maintained over the follow-up period, but few further improvements were made. Clinical significance was evaluated by both the subjective evaluation method and the social comparison method. These procedures indicated that although significant improvements had been made, these avoidant Ss were not functioning at the level of normative comparison samples at treatment termination. PMID- 2600247 TI - Personality disorders classification and symptoms in cocaine and opioid addicts. AB - The extent to which personality disorders (PDs) and associated symptom criteria were found among 117 cocaine- and opioid-dependent men selected from 350 consecutive inpatient admissions to a Veterans Administration Drug Dependence Treatment Unit over a 30-month period was examined using structured interview methodology. Drug groups were distinguished by higher rates of antisocial and borderline symptomatology rather than by features associated with other PDs. Cocaine users showed lower rates of borderline and adult antisocial features and reported less subjective distress than opioid addicts, and different constellations of target problem features emerged for the two groups. PMID- 2600248 TI - Marital distress, depression, and attributions: is the marital distress attribution association an artifact of depression? AB - We examined whether the association between marital distress and attributions is an artifact of depression. Study 1 showed that the attributions of 40 wives recruited from the community accounted for variance in their marital satisfaction after the effects of depression had been taken into account. Study 2 compared the attributions of 20 clinically depressed and maritally distressed wives (respondents to an advertisement offering therapy for depression and marital problems), 20 nondepressed but distressed wives (clients seeking marital therapy at a clinic), and a control group of 20 nondepressed and nondistressed wives (respondents to an advertisement for participants in a research project). The first two groups did not differ in attributions, but the attributions of both groups differed from those of the control group. Both studies therefore suggest that the association between attributions and marital satisfaction is not due to depression. PMID- 2600249 TI - The specific psychopathology of bulimia nervosa: a comparison with restrained and unrestrained (normal) eaters. AB - The hypothesis that patients with bulimia nervosa and restrained eaters exist on a simple continuum of psychopathology was tested in 60 Ss (20 bulimics, 20 restrained eaters, 20 unrestrained eaters). Regarding measures related to dieting behavior and physical appearance, the restrained eaters differed significantly from unrestrained eaters and were similar to bulimic patients except for level of psychopathology. The restrained eaters could not be distinguished from the unrestrained eaters with regard to measures representing interoceptive perception, depression, self-esteem, and fears about interpersonal relationships. On these traits, bulimic patients could be clearly distinguished from the normal Ss. The results support a 2-component model of the psychopathology of bulimia nervosa. PMID- 2600250 TI - Cognitive-behavioral therapy with and without exposure plus response prevention in treatment of bulimia nervosa: comment on Agras, Schneider, Arnow, Raeburn, and Telch. PMID- 2600251 TI - Cognitive-behavioral treatment with and without exposure plus response prevention in the treatment of bulimia nervosa: a reply to Leitenberg and Rosen. AB - In this reply to Leitenberg and Rosen (1989), we conclude that the evidence that response prevention of vomiting adds significantly to the efficacy of cognitive behavioral treatment of bulimia nervosa is not strong. In this context and given the finding in our previous study (Agras, Schneider, Arnow, Raeburn, & Telch, 1989) that the addition of response prevention did not increase the efficacy of cognitive-behavioral treatment and may have reduced it, we believe that our cautionary note concerning the addition of response prevention to cognitive behavioral treatment should stand. PMID- 2600252 TI - The microflora associated with the development of initial enamel decalcification below orthodontic bands in vivo in children living in a fluoridated-water area. AB - Thirty-four caries-free teeth destined for orthodontic extraction were banded to provide a protected area for the accumulation of plaque. The teeth were extracted at one, two, four, eight, and 14 days after being banded, and samples of the flora below the band were analyzed for the presence of Streptococcus sanguis, Streptococcus 'mitior', 'mutans streptococci', Actinomyces viscosus, Actinomyces naeslundii, Actinomyces odontolyticus, Lactobacillus species, and Veillonella. After plaque sampling, the teeth were sent to the Royal Dental College (Copenhagen) for histological analysis. The results showed that S. mutans could colonize the area below the band after one day, but that colonization was only 100% at 14 days. Lactobacillus was only isolated from 2/8 samples at four days and from 4/8 samples at 14 days. S. sanguis and 'S. mitior' were regularly isolated at all banding times, and Veillonella was isolated from all samples. A. viscosus was the most commonly isolated Actinomyces. The numbers of Streptococcus and Veillonella were significantly higher at day 1 than at day 14 (p less than 0.05). S. mutans and A. viscosus were isolated more frequently at day 14 than at day 1 (p less than 0.01). Histological examination revealed that dissolution of the enamel below a band could occur after two days, but that even after 14 days dissolution could be questionable. Dissolution was detected in areas where S. mutans was not isolated (8/34), but S. mutans was also present in samples showing dissolution (12/34). There was no relationship between dissolution and the numbers of S. mutans; however, the isolation frequency of S. mutans was associated with dissolution (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600253 TI - The effect of chronic atropine treatment on salivary composition and caries in rats. AB - Many instances of salivary dysfunction in humans can be traced to the use of medications that have hyposalivary side-effects. In this study, atropine, a cholinergic antagonist, was administered chronically to rats by use of osmotic mini-pumps. Steady-state blood levels, similar to levels obtained in human multiple oral dosing, were thus maintained. Atropine delivered in this manner for 24 days was found to decrease protein concentration of parotid saliva (p less than 0.05) elicited by pilocarpine, and to increase smooth-surface caries scores (p less than 0.05) in rats fed a cariogenic diet. Parotid saliva collected via ductal cannulation from rats subjected to chronic atropine administration (and stimulated to secrete by pilocarpine) exhibited increased levels of two basic proline-rich proteins (Peak A and SP-3), as evaluated by SDS-PAGE, compared with those observed in saliva from controls. Cannulation of sublingual glands in animals receiving high doses of atropine produced no measurable secretion upon pilocarpine stimulation. Carbachol stimulation of dispersed cell aggregates of sublingual glands from sham-operated and high-dose atropine groups indicated that the glands responded similarly once the antagonist was washed from the system, implying that the lack of secretion in vivo was caused by antagonism of the cholinergic receptor by atropine. Our observations suggest that this model system can be exploited for determination of the effects of chronic administration of hyposalivary drugs on salivary composition and caries rates. PMID- 2600254 TI - Effect of force level on synthesis of type III and type I collagen in mouse interparietal suture. AB - Nine-week-old Swiss male white mice were divided into groups killed after time intervals of force application of six h, and one, three, five, seven, ten, 14, 21, and 28 days. Each group had 45 animals: three control, three sham-operated, and three experimental animals for each of the five force levels: 50 g, 35 g, 25 g, 15 g, and 5 g. The experimental animals had helical springs placed surgically in their calvaria for expansion of the interparietal suture. The sham-operated animals received inactive springs. Control animals were at the same age as the experimental and sham-operated animals. After death, the amount of sutural expansion was measured, and the calvaria with the implanted springs were explanted into Trowell-type organ culture dishes. [14C]-glycine was added for two h after 60 min of culture for all explants. The rate of suture expansion was directly proportional to the force value of the tensile stress, and a maximum 2.0 mm expansion was achieved for all force levels by the 28th day. Sutural collagen was solubilized by limited pepsin digestion, and radiolabeled types I and III alpha-chains were separated by SDS-PAGE, visualized fluorographically, and measured densitometrically. All the experimental and sham-operated animals responded with a rapid rise followed by an almost equally rapid fall in the proportion of newly-synthesized type III collagen before becoming stabilized for the rest of the experimental period at a level that was significantly higher than that of the control and sham-treated animals of the same age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600255 TI - Quantitative in vivo wear of human enamel. AB - In this study, the attrition wear, also called occlusal-contact-area wear, of human enamel was measured quantitatively with a computerized three-dimensional measuring technique over a period of four years. Tooth replicas from a clinical trial were used. A running-in wear period after restorative treatment, followed by steady-state wear, was suggested. The average steady-wear rate on occlusal contact areas was about 29 microns per year for molars and about 15 microns per year for premolars. PMID- 2600256 TI - Performance assessment of colorimetric devices on dental porcelains. AB - The selection of an appropriate material that duplicates the appearance of natural tooth structure is very important in restorative dentistry. Photometric and colorimetric analysis techniques offer great potential as a tool for aiding in the duplication process. The degree to which these techniques will be useful depends on the accuracy and precision with which they can be applied to translucent as well as opaque surfaces. The purpose of this investigation was to evaluate the performance of three currently-available photometric devices. The performance capabilities of the instruments were tested on various shades of opaque and translucent dental porcelain surfaces. The performance tests were designed for evaluation of the accuracy and precision of the instrument relative to a well-studied reference instrument. CIELAB color difference metrics were used for the performance analysis. The results revealed that each of the photometric instruments evaluated was capable of producing color measurements with precision. However, the degree of accuracy with which the color measurements were made varied depending on the instrument used and the type of material surface being measured. A photo-electric tristimulus colorimeter showed the best overall performance on the porcelain surfaces, supporting its use as a valuable tool for evaluating color in dentistry. PMID- 2600257 TI - Visual and instrumental colorimetric assessments of small color differences on translucent dental porcelain. AB - The CIELAB colorimetric system was used for the study of the relationship between measured color difference values and human observer responses. This study verified that a specific, visually meaningful and precise relationship exists between the magnitude and direction of the measurements and the average dental observer responses. The results support the use of this system in dentistry as a means of evaluating color by differences. The further development of such systems for clinical use would be warranted and could serve as a valuable tool for material selection and restoration design, particularly in the area of aesthetic restorative dentistry. PMID- 2600258 TI - Comparison of jaw-muscle bite-force cross-sections obtained by means of magnetic resonance imaging and high-resolution CT scanning. AB - Cross-sectional areas of the jaw muscles were determined by means of magnetic resonance imaging (MRI) in 12 healthy adult male subjects. These findings were compared with the cross-sectional areas of the jaw muscles of the same subjects, obtained by means of computer tomography (CT) in a previous study (Weijs and Hillen, 1985). Significant correlations (r greater than 0.7) were found between the CT and MRI cross-sections of the masseter, medial pterygoid, and temporalis muscles. The low correlation between the CT and MRI cross-sections of the lateral pterygoid muscle could be explained by the different imaging techniques (slice thickness) of MRI and CT scanning. CT and MRI cross-sectional areas of the masseter and medial pterygoid muscle (but not the temporalis muscle) showed highly positive and significant correlations with the maximal voluntary bite force. In living subjects, the cross-sections of the masseter and medial pterygoid muscles can be visualized with CT and MRI. Compared with CT, MRI has some advantages, such as the absence of adverse effects (no radiation) and the excellent soft-tissue imaging. Furthermore, a series of frontal, horizontal, sagittal, and angulated MRI scans can be made without modification of the patient's position, facilitating reconstruction of the jaw muscles. PMID- 2600259 TI - Dental caries in adult and elderly Chinese. AB - This paper reports on a study of dental caries conducted among 1744 urban and rural Chinese (from 20 to 80 years old), who were selected by means of a systematic stratified sampling procedure. The prevalence of one or more decayed or filled teeth ranged from 48 to 90% in urban residents, and from 51 to 97% in rural residents, depending on age. The mean number of decayed or filled teeth ranged from 1.2 (+/- 1.9) among 20-29-year-olds, to 6.2 (+/- 5.5) among 70+-year olds, and was highest among rural residents. Among 20-29-year-olds, the main components of the DFT were enamel lesions and fillings. Among 30-49-year-olds, the DFT consisted mainly of enamel lesions and filled teeth, as well as teeth with lesions involving the pulpal tissues. In subjects over the age of 50 years, lesions involving pulpal tissues were the predominant type, followed by root surface lesions. In subjects below the age of 50 years, most of the caries experience derived from coronal surfaces, particularly occlusal surfaces. Root surface caries was predominantly a feature of persons aged 50 years and above. Despite a large number of surfaces being at risk of root-surface caries, less than 10% of the surfaces were so affected. Although cross-sectional in nature, these data indicate that when the oral hygiene standards are poor, caries lesions continue to develop and progress throughout life. With age, dental caries becomes a substantial oral health problem in this population of adult and elderly Chinese, despite the availability of some dental services. PMID- 2600260 TI - Cohort effects in the prevalence of caries in child populations in Tanzania. AB - In 1984, a four-year mixed-longitudinal study of oral health was begun in Morogoro Town and Morogoro District, Tanzania. Its main goal was to detect a possible upward trend in prevalence of caries in child cohorts in this developing country. The sample consisted of 722 seven- to nine-year-olds in 1984, 833 seven- to 11-year-olds in 1986, and 989 seven- to 13-year-olds in 1988. Mixed longitudinal studies provide the opportunity for application of the Age-Period Cohort analysis. On the basis of external information, either age and/or cohort and/or period effects can thus be isolated. Apart from significant age and period effects, a cohort effect was found, indicating that the prevalence of caries has decreased in these child populations between 1984 and 1988. PMID- 2600261 TI - The measurement of toothbrush wear. AB - Toothbrushes wear out and progressively lose their ability to clean as the bristles abrade and become curled and matted. To study the factors that influence this process, we developed a quantitative measure of bristle splaying (wear index) and a method for judging and ranking the overall state of brush deterioration (wear rating) and used these to determine the effects of the individual user, brush design, time in use, and bristle material. Wear index is the average increase in brush-head dimensions normalized for maximum bristle length, and is dimensionless. Wear rating is a subjective means of classifying the increasing severity of deterioration on a scale of 0 to 3. The wear characteristics of a variety of commercial and experimental brushes with different design features were determined. Test variables were time in use, brush design (e.g., geometry and size of the brush head), and bristle composition. Time of use, the individual user, and bristle composition were found to have the strongest influences on splaying, and brush design was found to have the least influence. The wear index offers a quantitative means of comparing brushes of different dimensions at various stages of splaying. The wear rating, although qualitative, is a quick means of ranking brushes in various stages of deterioration. The two methods correlate (R2 = 0.87), and both are sensitive to several factors that affect brush durability. Therefore, these methods appear to be suitable not only for research, but also for quality control, the setting of standards, and for substantiation of advertising claims. PMID- 2600262 TI - Effects of varnishes containing chlorhexidine on the human dental plaque flora. AB - This study describes the effects of varnishes containing 0%, 10%, 20%, or 40% chlorhexidine diacetate on the microflora of human fissure dental plaque. Sandarac, a natural resin, was used as the varnish base. Ten subjects, each with at least four sound fissures harboring high levels of Streptococcus mutans, participated in the study. The fissures in each of the individuals were randomly assigned to four experimental groups, in each of which one of the varnishes was tested. The varnish treatment consisted of a single application of a small amount of varnish onto the fissures. Apart from the selected fissures, the rest of the dentition was left untreated. All chlorhexidine-containing varnishes selectively suppressed S. mutans in fissure plaque, and had no effect on total viable counts or on the numbers of Actinomyces viscosus/naeslundii and Streptococcus sanguis beyond one week. The extent of the suppression depended upon the concentration of chlorhexidine in the varnish, 40% chlorhexidine varnish giving the greatest suppression of S. mutans. At 22 weeks, after a single treatment with varnish containing 40% chlorhexidine, mean S. mutans counts were more than ten times lower than in the control or 10%-chlorhexidine varnish group. At that time, S. mutans was still undetectable in five out of ten experimental fissures in this group. The results suggested that sandarac varnishes containing high concentrations of chlorhexidine can be used successfully for long-term suppression of S. mutans in dental fissures. PMID- 2600263 TI - Developmental biology and pathobiology: fusion through molecular biology. PMID- 2600264 TI - Azadirachtin as a larvicide against the horn fly, stable fly, and house fly (Diptera: Muscidae). AB - Effects of azadirachtin, a triterpenoid extracted from neem seed, Azadirachta indica A. Juss., were similar to those of insect growth regulators against the immature stages of the born fly, Haematobia irritans (L.), the stable fly, Stomoxys calcitrans (L.), and the house fly, Musca domestica L. When an ethanolic extract of ground seed was blended into cow manure, LC50 and LC90's for larval horn flies were 0.096 and 0.133 ppm azadirachtin, respectively. An emulsifiable concentrate (EC) had an LC50 for larval horn flies of 0.151 ppm and an LC90 of 0.268 ppm. For larval stable flies, the EC formulation had an LC50 of 7.7 ppm and an LC90 of 18.7 ppm azadirachtin in manure. Against larval house flies, the LC50 and LC90 were 10.5 and 20.2 ppm, respectively. When the EC formulation was administered orally to cattle at a rate of greater than or equal to 0.03 mg azadirachtin per kg of body weight per day or when ground neem seed was given as a daily supplement of greater than or equal to 10 mg seed per kg body weight, horn fly development in the manure was almost completely inhibited. In contrast, ground seed mixed in cattle feed at the rate of 100-400 mg seed per kg of body weight per day caused less than 50% inhibition of stable flies in the manure. PMID- 2600265 TI - Abnormal division and gene expression in cultured cells from a patient with tuberous sclerosis. AB - Tuberous sclerosis is a dominant hereditary disease characterized by the appearance of angiofibromas on the face, epileptic attacks, and mental retardation. Attention has been paid to the atypical cells observed histologically in the stroma of the angiofibroma as they may play an important role in forming lesions. We have established a cell line from an angiofibroma to clarify the nature of these cells at the cellular and biochemical levels. The cultured cells have been stably maintained for four years and show an abnormal morphology resembling that of neuronal cells. In culture, these cells divide into daughter cells, which consist of both normal cells and abnormal ones whose nuclei disintegrate and cannot divide further. The cells resemble normal fibroblasts in their pattern of staining with antibodies against tubulin, actin, vimentin, and fibronectin. However, they also stain with an antibody against the glia-specific acidic protein, which is thought to be a specific marker protein for glial cells. The gel profile of cyclic-AMP binding proteins was not fibroblastic, but rather of the neuron cell type. These results indicate the gene expression of these cells is also abnormal. They are a useful tool for understanding this specific genetic disease. PMID- 2600266 TI - Comparison of human hair and nail low-sulfur protein compositions on two dimensional electrophoresis. AB - Compositions of human normal hair and nail low-sulfur proteins were compared using two-dimensional electrophoresis of their S-carboxymethylated (SCM) derivatives. Six SCM low-sulfur protein components with molecular weights (MWs) of 76,000, 73,000, 72,000, 64,000, 61,000 and 55,000 were common to the hair and nail. One component with a MW of 61,000 was specific to hair, and two components, both with a MW of 50,000, were specific to nail. PMID- 2600267 TI - Light microscopic and transmission electron microscopic investigations of the stratum corneum of xerosis vulgaris of the leg. AB - Histopathological findings from eight cases of xerosis vulgaris of the leg (XVL) were compared to those from nine normal controls using light microscopy and one micron epoxy resin-embedded sections stained with toluidine blue and basic fuchsin (T-F) and electron microscopy with ultra-thin sections. Three sub-layers were identified in the stratum corneum of all cases of XVL and normal controls by differences in color in T-F stained specimens and by differences in density in electron microscopic findings. Electron microscopically, the intermediate sub layer within the three-layered structure showed an uneven density with many empty spaces in both normal controls and cases of XVL. Statistically, only the intermediate sub-layers of XVL increased significantly in number (p less than 0.05) as well as in thickness (p less than 0.001), compared to normal controls. These findings suggest that the intermediate sub-layers play an important role in holding water in the skin. PMID- 2600268 TI - Flow cytometric analysis of murine splenic cells after DNFB painting on Langerhans cell deficient skin. AB - One week after a single painting of 50 microliters of 0.5% DNFB in acetone-olive oil on the tail skin of C3H mice, the spleens were removed from the animals. A single cell suspension was prepared from the spleens, and flow cytometric analysis was performed for L3T4 and Lyt2 positive cells, as well as for the IJk expression of the Lyt2+ cells. Results showed that the percentages and absolute numbers of Lyt2+ L3T4- cells, Lyt2- L3T4+ cells, Lyt2+ IJk+ cells, and Lyt2+ IJk- cells in the spleens of the DNFB-treated mice were not significantly different from those in the non-treated mice. However, in the treated mice, the IJk expression of Lyt2+ cells intensified. These results indicate that, following a single painting of DNFB onto Langerhans cell-deficient skin, the numbers of Lyt2+ cells do not change significantly, but do change functionally. PMID- 2600269 TI - Cutaneous sarcoidosis showing multiple papular eruptions with keratotic plugs. AB - A 26-year-old woman developed 249 discrete papules on her lower extremities. Twenty-three of them had keratotic plugs. Histologic examination demonstrated granulomatous foci consisting of epithelioid cells and a epidermal invagination which was disrupted at the base and lateral sites. This invagination was considered to represent transepithelial elimination. PMID- 2600270 TI - Pigmented basal cell carcinoma developing on the lower extremities--three cases masquerading as malignant melanoma. AB - Three cases of pigmented basal cell carcinoma were reported which needed to be differentiated from malignant melanoma based on their location and clinical features. Clinicopathologically, they were characterized by a large number of melanophages in the stroma, blockade melanocytes in the parenchyma, and phagocytosis of melanosomes in tumor cells as well as a large number of intraparenchymal melanophages. Two cases were characterized by the aggregation of melanophages in cystic spaces caused by stellate atrophy. PMID- 2600271 TI - Correlation of Aedes albopictus bite reaction with IgE antibody assay and lymphocyte transformation test to mosquito salivary antigens. AB - To investigate the mechanisms responsible for mosquito bite reaction, 120 subjects were experimentally exposed to Aedes albopictus bite and two types of immunological tests were performed. Specific IgE antibodies to salivary gland extract (SGE) antigens of female Aedes albopictus were measured by enzyme-linked immunosorbent assay (ELISA) in all subjects. Lymphocyte transformation tests (LTTs) to the same antigens were measured in 51 of the 120 subjects. The relationships between the results of ELISA and LTTs with bite reactions were statistically analysed. The amount of specific IgE antibodies correlated well with immediate bite reactions (r = 0.55) (p less than 0.01). Stimulation indices (SIs) to SGE antigens correlated with delayed bite reactions (r = 0.54) (p less than 0.01). The results suggest that type I hypersensitivity plays a role in the immediate reaction to mosquito bites and a cellular immune mechanism is responsible for the pathogenesis of delayed bite reactions. PMID- 2600272 TI - Flow cytometric analysis of protein kinase C in lymph node cells during the induction phase of contact hypersensitivity reaction. AB - On the fourth day after a single painting of 2,4,6-trinitro-chlorobenzene on the abdominal skin, inguinal lymph nodes were removed, and a single-cell suspension was prepared. The cells were analyzed flow cytometrically, using monoclonal anti protein kinase C antibody. It was found that the number of lymph node cells in which protein kinase C was detected on the cell surface was significantly increased over that in non-treated mice (p less than 0.01). On the basis of our results and discussions in the literature, it is thought that protein kinase C is related to the initiation of the contact hypersensitivity reaction. PMID- 2600273 TI - Establishment of a human dermatofibrosarcoma protuberans cell line: cytological characteristics. AB - We established a dermatofibrosarcoma protuberans (DFSP) cell line derived from a DFSP tumor from a 69-year-old female. The population doubling time of the cells was about 45 hours. The cells were mostly round, although a few triangular or spindle-shaped cells were also found. They could not be transplanted into nude mice. These cells had some histiocyte characteristics which are not observed in fibroblasts: 1) Electron microscopically, there were more lysosomes and phagolysosomes than in fibroblasts. Dense bodies and myelin figures derived from lysosomes were also observed. 2) Staining with acid phosphatase (ACPase), esterase, and alpha-1-antitrypsin was positive. 3) The cells had C3 receptors but no Fc receptors. However, there were two differences between DFSP cells in the established line and those in the early stages: in the former, the capacity for immunophagocytosis (Fc receptors and phagocytosis of Candida albicans) and collagen synthesis were almost entirely absent. PMID- 2600274 TI - Erythema multiforme in children: unusual clinical features with seasonal occurrence. AB - Eighty-six cases of erythema multiforme (EM) were studied based on the distribution of skin lesions. Twenty-nine patients had distinct facial skin lesions as well as lesions on the extremities (Group A) and 57 patients had skin lesions only on the extremities (Group B). Patients in Group A were younger than those in Group B; the average ages being 7.5 and 25.2 years, respectively. In Group A, the disease occurred mainly in winter, while, in Group B, it began most frequently in summer. Preceding ulcerated pernio was seen in 11 patients of Group A, but only one of Group B. Histopathologically, both groups are compatible with a diagnosis of EM, although the seasonal occurrence of facial involvement in Group A may suggest a specific etiological relationship to cold. PMID- 2600275 TI - Cutaneous mucinosis associated with SLE--a case provoked by PUVA. AB - A patient with SLE which was complicated by a characteristic cutaneous mucinosis is reported. The skin lesions were composed of intradermal soft nodules, purple red plaques, and alopecia of the scalp. Acid mucopolysaccharides accumulated in each lesion. PUVA provoked an infiltrated skin lesion in which acid mucopolysaccharides were deposited in the dermis. Deposition of immunoglobulins and complements were also observed at the dermo-epidermal junction and on the vascular walls. Some immunological processes which may stimulate the synthesis of acid mucopolysaccharides in the dermis were suggested. PMID- 2600277 TI - Eosinophil-infiltrating folliculitis in childhood--report of a case. AB - A 5-year-old Japanese girl developed follicular pustules with erythematous plaques on the lower extremities. The histopathology was compatible with eosinophilic pustular folliculitis (EPF). However, the clinical findings were not typical of EPF; the pustules did not appear in crops, the pustules became ulcers, and the skin lesions appeared exclusively on non-seborrheic areas. PMID- 2600276 TI - Lupus erythematosus profundus--report of a case treated with dapsone. AB - A male adult patient with discoid lupus erythematosus (DLE) developed lupus erythematosus profundus. We decided to treat him with oral administration of dapsone, which proved to be very effective. PMID- 2600278 TI - Verruciform xanthoma on the scrotum. AB - A case of 80-year-old man with a verruciform xanthoma on the right side of the scrotum was reported. The tumor was examined histologically by light and electron microscope. We surveyed the literature and found 25 Japanese cases and 11 foreign cases in the skin. We also reviewed the pathogenesis and the location of this disease. PMID- 2600279 TI - A case of solitary mastocytoma suggesting a divided form of mast cell nevus. AB - The case of a 10-week-old boy with a solitary mastocytoma is reported. The lesion, noticed at birth, was located in an area extending from the dorsum of the left hand to the proximal phalanx of the ring and little fingers. It appeared as a coin-sized, flattened dome-shaped, round tumor with occasional blistering. The web between the two fingers was free of cutaneous changes. The diagnosis was confirmed by the histological characteristics: a densely mastocytic infiltration into the dermis. The present case of solitary mastocytoma, referred to as "mast cell nevus", is unique because of its previously undescribed divided form. PMID- 2600280 TI - Malignant hidroacanthoma simplex. AB - A case of malignant hidroacanthoma simplex is described. Histological examination revealed that the malignant cells had arisen from a tumor cell nest of benign hidroacanthoma simplex and invaded the dermis. Two years and 7 months after the excision of the original thigh lesion, a groin lymph node metastasis was discovered. The metastatic tumor cells in the lymph node were histologically similar to the carcinoma cells in the original thigh lesion and had enzymatic and ultrastructural features resembling eccrine sweat duct. PMID- 2600281 TI - Congenital alveolar rhabdomyosarcoma presenting as a blueberry muffin baby. AB - Congenital alveolar rhabdomyosarcoma in a newborn was reported. She had multiple subcutaneous tumors and looked like a blueberry muffin baby. From the clinical signs and the histological pictures, a diagnosis of neuroblastoma was considered. Laboratory data showed no abnormalities. Electron microscopic examination revealed myofilament and incipient stria formation. On the basis of these data, a final diagnosis of congenital alveolar rhabdomyosarcoma associated with multiple skin metastases was made. PMID- 2600282 TI - The changing challenges of critical care. PMID- 2600283 TI - Infection prevention by selective decontamination in intensive care. PMID- 2600284 TI - Use of catecholamines in CPR. PMID- 2600285 TI - Leukotrienes and ARDS. PMID- 2600286 TI - Comparison of epinephrine and dopamine during cardiopulmonary resuscitation. AB - The effectiveness of epinephrine and dopamine for restoring spontaneous circulation after asphyxial or fibrillatory cardiac arrest was compared using a porcine model. Asphyxial arrest: 7 animals received 45 micrograms/kg epinephrine, 7 animals 2.5 mg/kg dopamine, the remaining 7 animals received no drug treatment. All 7 animals given epinephrine could be resuscitated after 174 +/- 53 s, spontaneous circulation could be restored in only 3 of 7 animals given dopamine after 487 +/- 63 s and in none of the control animals could spontaneous circulation be established. Ventricular fibrillation: 7 animals were defibrillated without either mechanical measures or drug therapy. The following doses were given before defibrillation and after starting mechanical measures to separate groups of 7 animals each: 45 micrograms/kg epinephrine, 2.5 mg/kg dopamine, or no drug therapy. In the absence of either drug or mechanical measures and with mechanical measures only, spontaneous circulation could not be established in any of the cases. After administration of epinephrine, defibrillation and restoration of spontaneous circulation was achieved in 6 of 7 animals in 667 +/- 216 s, with dopamine, all the animals could be successfully resuscitated in the shorter time of 174 +/- 85 s. Epinephrine was found to be superior to dopamine in the treatment of asphyxial arrest whereas dopamine was found to be better in the management of ventricular fibrillation, probably by improving the balance between myocardial oxygen supply and demand. PMID- 2600287 TI - Differential evaluation of bronchoalveolar lavage cells and leukotrienes in unilateral acute lung injury and ARDS patients. AB - Patients with unilateral acute lung injury (UALI; n = 6) and ARDS (n = 4) were evaluated by bronchoalveolar lavage, as controls we used 5 patients suffering from cerebral hemorrhage and without pulmonary, cardiac or infectious disease who were mechanically ventilated. For each group of patients two independent bronchoalveolar lavages (BAL) were performed. The BAL fluid recovered from the two lungs was immediately analyzed for leukotrienes (LTS) by means of RP-HPLC and stained for cell counts. The BAL from the control group did not show any LTS and the percentage of neutrophils was within the normal range: 1 +/- 0.2% right lung and 1.2 +/- 0.4% left lung. The BAL fluid from UALI patients showed two different patterns, the injured lung showed high levels of LTS (39.1 +/- 8 ng ml-1 LTB4; 25 +/- 6 ng ml-1 LTD4 and 27.8 +/- 8.2 ng ml-1 11-trans LTC4) and an increased percentage of neutrophils (74.2 +/- 7%) compared to controls. Only 2 out of the 6 patients from the UALI group showed small amounts of LTB4 (4 ng ml-1) and LTD4 (3.2 ng ml-1). The BAL obtained from the "healthy lung" in both cases showed values of LTS almost eight fold lower than those present in the injured lung. The percentage of neutrophils from the unaffected lungs (4.3 +/- 7%) was not significantly different from controls. Lavage fluid from ARDS patients showed a similar picture to that of the affected lung from UALI patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600288 TI - Continuous multi-channel intravascular monitoring of the effects of dopamine and dobutamine on plasma potassium in dogs. AB - The effects of dopamine and dobutamine on plasma potassium were investigated in dogs using continuous, multi-channel, intravascular ion-selective potassium electrodes situated in the aorta and abdominal and thoracic inferior vena cavae. Doses of 10 and 30 micrograms kg-1 min-1 of each drug were used, and the effects on potassium compared with isoprenaline 0.07 and 0.2 microgram kg-1 min-1. Both the drugs caused a biphasic pattern of potassium change consisting of an initial small rise in the potassium level, followed by a sustained period of hypokalaemia. The changes were greater with the higher dose of each drug compared with the lower dose, but there were no significant differences between the drugs. Comparison of the potassium changes between the three vascular sites studied suggested that the rise in potassium may be a result of release of the ion from the liver, and that the liver may also be the principle site of potassium uptake during the hypokalaemic phase. PMID- 2600289 TI - The effects of beta blockade on dopamine and dobutamine induced hypokalaemia in dogs. AB - The effect of beta 1 and beta 2 blockade on dopamine and dobutamine induced hypokalaemia was investigated in dogs. Arterial plasma potassium was continuously monitored using a potassium-sensitive electrode sited in the abdominal aorta. Dopamine and dobutamine were infused at 15 micrograms kg-1 min-1 into animals pre treated with atenolol (0.5 mg kg-1) or ICI 118551 (0.5 mg kg-1) and the potassium changes compared to those seen in control animals. The inotrope infusions caused a small and transient rise in plasma potassium (p less than 0.05) followed by a more profound hypokalaemia (p less than 0.05) sustained for the duration of the infusion. The potassium falls in the control animals were similar to those in the beta 1 and beta 2 blockade groups. The results suggest that beta 2 receptor stimulation cannot alone be responsible for dopamine and dobutamine induced hypokalaemia and a multiple receptor activation is postulated. PMID- 2600290 TI - Monitoring lung mechanics and airway pressures during differential lung ventilation (DLV) with emphasis on weaning from DLV. AB - Fifteen polytrauma patients with asymmetric pulmonary contusion were treated with differential lung ventilation (DLV) for a mean of 106 hours (range 24-298, median 83). The differential time constant (Tc), compliance (Ct), inspiratory and expiratory airway resistance (Rawinsp, Rawexp) and peak-airway pressure (Pawpeak) were monitored to evaluate the function of each lung. Values measured after starting DLV were compared to those obtained prior to stopping DLV in order to analyse whether these parameters had returned to symmetrical values when recommencement of conventional mechanical ventilation was considered on clinical parameters and also whether these could be useful criteria for weaning from DLV. The significant difference in Tc of the contused lung compared to the contralateral lung after starting DLV is mainly determined by altered Ct resulting from contusion. During DLV improvement of Ct resulted in identical Tc of both lungs prior to stopping DLV. Changes in the Rawinsp contributed little to changes in Tc. Identical Tc prior to stopping DLV coincided with identical Pawpeak on symmetrical ventilator settings. These data suggest that when less advanced monitoring equipment is available, the differential Pawpeak might be used as a measure of differential lung mechanics in asymmetrical pulmonary contusion. PMID- 2600291 TI - Fluid requirements of patients with burns and inhalation injuries in an intensive care unit. AB - We have studied 9 patients with burns (20%-75%) who had inhalation injuries and compared their actual fluid requirements with their requirements calculated from the Muir and Barclay formula. All patients were resuscitated with plasma protein fraction at a rate sufficient to keep their physiological variables within the following range: heart rate less than 120/min, central venous pressure 8-12 cm H2O, urine output greater than 30-50 ml/h, systolic blood pressure greater than 90 mm Hg and diastolic blood pressure greater than 60 mm Hg. The amount of plasma protein fraction needed was 4.38 +/- 1.26 ml/kg/% burn in the first 24 h and 2.15 +/- 0.97 ml/kg/% burn in the second 24 h. This is an increase of 75% and 110% respectively above values predicted from the formula. We suggest that the observed difference is due to a combination of the presence of an inhalation injury which increases fluid requirements by approximately 30% in the first 24 h and the use of plasma protein fraction rather than the dried plasma used in the original Muir and Barclay formula. PMID- 2600292 TI - A clinical sickness score for the critically ill in Central Africa. AB - Scoring systems provide a means for comparing results, ensuring consistent standards and evaluating changes in therapy. The APACHE II system depends partly on the results of laboratory tests which are not normally available in Central Africa. The aim of this study was to develop a scoring system based only on clinical observations. Six hundred and twenty-four consecutive admissions to the intensive care unit (ICU) were allocated a clinical sickness score (CSS) according to pulse rate, blood pressure, respiration rate, urine output, Glasgow Coma Scale, temperature and age. CSS was significantly associated with outcome, there being no significant difference between actual and predicted outcomes calculated by logistic regression analysis. There was a significant difference between mean scores for survivors and non-survivors in all diagnostic groups except diabetes. The proportional change in score from admission was also significantly associated with outcome on each subsequent day in ICU. The CSS provides an objective measure of illness severity for critically ill patients in Africa. PMID- 2600294 TI - Assessment of adequate tissue oxygenation in shock and critical illness: oxygen transport in sepsis, Bermuda, April 1 + 2, 1989. PMID- 2600293 TI - Calcium free hemodialysis: an effective therapy in hypercalcemic crisis--report of 4 cases. AB - Hypercalcemic crisis represents a medical emergency. If conservative treatment is ineffective, low calcium bath or zero calcium bath hemodialysis are good alternatives. We report 4 patients treated with calcium free acetate hemodialysis because of hypercalcemic crisis due to breast cancer, hepatocellular carcinoma, cirrhosis of the liver and immobilisation with hydrochlorothiazids' medication. Following 3 h of hemodialysis, serum calcium concentrations fell from a mean value of 3.96 (range 3.53-4.46) mmol/l to 2.71 (2.28-3.12) mmol/l. In 2 patients rapid clinical improvement was achieved and in one oliguric patient diuresis started spontaneously during hemodialysis. One patient died from gram-negative sepsis. In 3 cases the subsequent conservative treatment was sufficient to maintain serum calcium levels within the normal range. Together with the previously reported cases (5 patients treated by hemodialysis with low dialysate calcium and 3 patients by hemodialysis with calcium free dialysate) our experience indicates that hemodialysis is an effective and safe therapy for hypercalcemic crisis. PMID- 2600295 TI - More on acute renal failure in the intensive care unit. PMID- 2600296 TI - Transesophageal echocardiography. PMID- 2600297 TI - Gastric pH and colonisation in sucralfate treated patients. PMID- 2600298 TI - The effect of H2 receptor antagonists on intragastric pH in critically ill patients. PMID- 2600300 TI - Apparent auditory deprivation effects of late onset: the role of presentation level. AB - Silman and colleagues [J. Acoust. Soc. Am. 76, 1347-1362 (1984)] have reported an apparent effect of late auditory deprivation; this presents as loss of discrimination over time in the unaided ear of individuals using a single hearing aid fitted in middle age. In a replication of the basic effect, the influence of presentation level was examined in 24 monaurally aided subjects. The effect was reversed at presentation levels below about 75 dB SPL. The ear that is normally aided performs better at high presentation levels, while, at lower presentation levels, the converse is true. Thus it appears that a form of selective adjustment takes place in a particular part of the dynamic range, at least in ears with a dynamic range limited by a sensory hearing loss. If this interpretation is correct, there are important implications for research on perceptual learning and for the time course of evaluation in hearing aid provision. PMID- 2600299 TI - Results for two children using a multiple-electrode intracochlear implant. AB - Assessments in speech perception, speech production, and language skills were conducted on two children, 5 and 10 years old at the time of surgery, using the Nucleus multiple-electrode cochlear implant. Data were collected pre- and post operatively to measure changes in performance over time. For closed-set speech perception tests in the audition alone condition, post-operative performance was generally better than pre-operative performance and performance improved post operatively for both patients. In closed-set vowel and consonant identification and open-set sentence perception for the older patient, post-operative improvements from the vision alone to the auditory-visual condition were recorded and performance improved post-operatively in both conditions. In all measures of speech production for both patients, post-operative scores were higher than pre operative scores and performance improved post-operatively. In language skills, post-operative scores were higher than pre-operative scores and scores improved post-operatively in all measures for both patients. PMID- 2600301 TI - The speech of a postlingually deafened teenager during the first year of use of a multichannel cochlear implant. AB - The speech of a profoundly postlingually deafened teenager was recorded before, immediately after, 3 months after, and 1 year after electrical stimulation with a Nucleus multichannel cochlear implant. Listener tests of target words revealed significant improvement in overall quality over the year. Spectrograms showed less aspiration and better definition of the lower formants. Acoustic measurements indicated immediate change in F0 and gradual changes in syllable duration and some aspects of voicing and manner of articulation. Vowel space shrank steadily over the year, with both first- and second-formant frequencies dropping. Prestimulation results are discussed relative to the literature on the speech of the congenitally hearing impaired. Effects of multichannel electrical stimulation on speech are compared with studies of single-electrode stimulation. PMID- 2600302 TI - Binaural processing of noisy stimuli: internal/external noise ratios for diotic and dichotic stimuli. AB - A set of ten digitized statistically similar Gaussian maskers was used in one internal tone-in-noise detection experiments under diotic (NoSo) and dichotic (NoS pi) interaural conditions. Stimulus/response matrices were generated for each masker in the presence or absence of a target 500-Hz tone. For both NoSo and NoS pi, nonparametric analyses show that response probabilities and sensitivities vary significantly across noise waveforms, indicating a considerable external noise component in subject response variability. A parametric model is developed that maps individual stimulus waveforms onto a decision axis, facilitating evaluation of internal/external noise variance ratios. For both NoSo and NoS pi, internal and external noise variance are of similar magnitude. PMID- 2600303 TI - Noise and vibration interactions: effects on hearing. AB - There is the suggestion in the literature that vibration may potentiate the effects of noise and may thus increase the risk of hearing loss in a variety of exposure situations. However, in human experimental studies, which, by necessity, are limited to low levels of exposure, the effects measured are relatively small. A very limited number of animal studies have also shown an enhanced noise-induced hearing loss in the presence of vibration, but the scope of these studies is limited. The animal studies (chinchilla) that form the basis of this report were performed using a 30-Hz, 3g rms and a 20-Hz, 1.3g rms cage vibration separately and in combination with continuous noise (95-dB, 0.5-kHz octave band) and impact noise (113, 119, or 125 dB peak SPL) exposure paradigms. All exposures lasted for 5 days. The impact noise exposures were designed to have approximately equal total energy. Temporary and permanent threshold shifts were measured using evoked potentials, and sensory cell loss was measured using surface preparation histology. The results obtained from some of the noise/vibration paradigms showed that such exposures can alter some of the dependent measures of hearing. This effect was statistically significant only for the stronger vibration exposure conditions and was evident primarily in the extent of the outer hair cell losses and in the shape of the PTS audiogram. PMID- 2600304 TI - Modulation interference in detection and discrimination of amplitude modulation. AB - Two experiments were conducted to assess the effect of the rate of sinusoidal amplitude modulation (SAM) of a masker tone on detection of SAM of a probe tone (experiment 1) or on SAM-rate discrimination for the probe tone (experiment 2). When modulated at the same rate as the probe, the masker interfered with both the detection of probe modulation and the discrimination of the rate of probe modulation. The interference was obtained when the masker was either higher or lower in frequency than the probe (the probe and masker were separated by 2 oct). The amount of interference in detecting probe modulation (experiment 1) decreased as the common base rate of modulation was increased from 5 to 200 Hz. For rate discrimination (experiment 2), the amount of interference remained approximately the same for base rates of 2-40 Hz, the range over which rate discrimination was measured. In both experiments, the amount of interference was reduced when the masker was modulated at a different rate than the probe. PMID- 2600305 TI - Segregation of concurrent sounds. I: Effects of frequency modulation coherence. AB - Frequency modulation coherence was investigated as a possible cue for the perceptual segregation of concurrent sound sources. Synthesized chords of 2-s duration and comprising six permutations of three sung vowels (/a/, /i/, /o/) at three fundamental frequencies (130.8, 174.6, and 233.1 Hz) were constructed. In one condition, no vowels were modulated, and, in a second, all three were modulated coherently such that the ratio relations among all frequency components were maintained. In a third group of conditions, one vowel was modulated, while the other two remained steady. In a fourth group, one vowel was modulated independently of the two other vowels, which were modulated coherently with one another. Subjects were asked to judge the perceived prominence of each of the three vowels in each chord. Judged prominence increased significantly when the target vowel was modulated compared to when it was not, with the greatest increase being found for higher fundamental frequencies. The increase in prominence with modulation was unaffected by whether the target was modulated coherently or not with nontarget vowels. The modulation and pitch position of nontarget vowels had no effect on target vowel prominence. These results are discussed in terms of possible concurrent auditory grouping principles. PMID- 2600306 TI - Within- versus cross-channel mechanisms in detection of envelope phase disparity. AB - These experiments were designed to examine the mechanism of detection of phase disparity in the envelopes of two sinusoidally amplitude-modulated (AM) sinusoids. Specifically, they were performed to determine whether detection of envelope phase disparity was consistent with processing within a single channel in which the AM tones were simply added. In the first condition, with an 8-Hz modulation frequency, phase-disparity thresholds increased sharply with an initial increase in separation of the carrier frequencies. They then remained approximately constant when the separation was an octave or above. In the second condition, with carrier pairs of 1 and 2 kHz or 1 and 3.2 kHz and a modulation frequency of 8 Hz, thresholds were little affected as the level of one carrier was decreased relative to the other. With a modulation frequency of 128 Hz, for most subjects there was more of an effect of level disparity on thresholds. In the third condition, when the modulation frequency was 8 Hz, subjects showed relatively constant thresholds whether the signals were presented monotically, dichotically, or dichotically with low- and high-pass noise. Dichotic thresholds were typically higher than monotic when the modulation frequency was 128 Hz. These results suggest that it is not necessary to have information available within a single additive channel to detect envelope phase disparity. In certain circumstances, a comparison across channels may be used to detect such disparities. PMID- 2600307 TI - Characterization of an EPSP-like potential recorded remotely from the round window. AB - The whole-nerve cochlear action potential (CAP), to tone burst stimulation, was recorded before and after application of tetrodotoxin (TTX) to the intact round window (RW) membrane. TTX abolished the CAP leaving a residual negative potential without altering the summating potential (SP) or the cochlear microphonic (CM). The residual potential retained its polarity when recorded from scala vestibuli. The peak latency, amplitude, and tuning properties of the residual potential showed features similar to the CAP. Application of kainic acid to the RW membrane eliminated the residual potential, leaving the SP and CM unaltered. It is hypothesized that the sources of the residual potential are the excitatory post synaptic potentials from the peripheral processes of afferent dendrites under the inner hair cells. PMID- 2600308 TI - Statistical and receiver operating characteristic analysis of empirical spike count distributions: quantifying the ability of cochlear nucleus units to signal intensity changes. AB - Analytical methods from signal detection theory were applied in an effort to quantify the ability of cochlear nucleus (CN) units to signal changes in intensity. Of particular interest was the relation between this ability and the different patterns of discharge that characterize auditory neurons. Single-unit responses to best-frequency (BF) tone bursts were recorded from neurons in the gerbil cochlear nucleus, and empirical spike-count distributions were generated. The mean-to-variance ratios for regular units were generally larger than those of irregular units. Receiver operating characteristic (ROC) curves were generated from empirical spike-count distributions. The area under the ROC curve [P(A)] was computed and used to define the performance of an observer detecting whether or not a change in firing rate has occurred, thus signaling a change in intensity. For a given change in mean spike count, units characterized by regular interspike interval (ISI) histograms typically gave larger P(A) values than did units characterized by irregular ISI histograms. In addition, onset units gave larger values of P(A) than did irregular units for a given change in mean spike count. These results suggest that regular and onset units are better able to signal intensity changes than are irregular units. PMID- 2600309 TI - Hazard from an intense midrange impulse. AB - It has been hypothesized that the ear would become increasingly susceptible to impulses (gunfire) as the spectral peak of the impulse approached the frequency region where the ear was tuned best (about 4 kHz for the cat ear) [G. R. Price, J. Acoust. Soc. Am. Suppl. 1 62, S95 (1977)]. This prediction was counter to the predictions of the world's damage-risk criteria for impulse noise. It has been supported by experiments using exposures to 100-Hz and 800- to 1000-Hz impulses; but no test had been run at the point of predicted maximum susceptibility. In the present experiment, three groups of cats were exposed to 50 impulses produced by a primer explosion (spectral peak at 4 kHz) at peak levels of 135, 140, or 145 dB. Auditory thresholds were electrophysiologically measured from the vertex to 2 , 4-, 8-, and 16-kHz tone pips and losses were determined 30 min after exposure and more than 2 months post-exposure. Losses were greatest at 4 kHz, began to develop at 134-dB peak pressure, and the immediate losses grew at a rate of about 7 dB for every dB increase in peak pressure. About half of the loss measured immediately became permanent. The energy required to begin producing a permanent threshold shift was only about 0.07 J/m2, far lower than that required with continuous noises at lower sound pressures. The data were interpreted as supporting the original hypothesis of greater susceptibility in the midrange. PMID- 2600310 TI - The responses of models of "high-spontaneous" auditory-nerve fibers in a damaged cochlea to speech syllables in noise. AB - The responses of four high-spontaneous fibers from a damaged cat cochlea responding to naturally uttered consonant-vowel (CV) syllables [m], [p], and [t], each with [a], [i], and [u] in four different levels of noise were simulated using a two-stage computer model. At the lowest noise level [+30 dB signal-to noise (S/N) ratio], the responses of the models of the three fibers from a heavily damaged portion of the cochlea [characteristic frequencies (CFs) from 1.6 to 2.14 kHz] showed quite different response patterns from those of fibers in normal cochleas: There was little response to the noise alone, the consonant portions of the syllables evoked small-amplitude wide-bandwidth complexes, and the vowel-segment response synchrony was often masked by low-frequency components, especially the first formant. At the next level of noise (S/N = 20 dB), spectral information regarding the murmur segments of the [m] syllables was essentially lost. At the highest noise levels used (S/N = +10 and 0 dB), the noise was almost totally disruptive of coding of the spectral peaks of the consonant portions of the stop CVs. Possible implications of the results with regard to the understanding of speech by hearing-impaired listeners are discussed. PMID- 2600311 TI - AP threshold elevation in the guinea pig following exposure to a broadband noise. AB - Sixty guinea pigs were exposed to a steady-state broadband noise with a falling frequency spectrum. The sound-pressure level was varied between 96 and 117 dB SPL, and the duration of the exposure was varied from 3 to 12 h. After 4-5 weeks, the auditory thresholds were determined by electrocochleography at 14 frequencies, and the results were compared with a control group. With increasing sound-pressure level, the thresholds became elevated at all frequencies. The maximum threshold elevation also exhibited a slight shift toward higher frequencies. With increasing exposure time, the threshold elevations increased and shifted into the high-frequency region, whereas the low-frequency region was less affected. Linear regression analysis showed that the average threshold elevation between 1 and 20 kHz did not deviate from that predicted by the equal energy hypothesis. However, the high-frequency loss at 5-20 kHz was very dependent on the exposure time, whereas the 1- to 4-kHz loss was not. There was no sign of any critical intensity with sudden increments in threshold elevation. PMID- 2600312 TI - Experimental frequency spectra of ultrasound transmission through two-dimensional ensembles of trapped microbubbles. AB - The frequency spectra of transmission coefficients for ultrasound passing through a sheet of gas-filled micropores have been measured using incident waves with amplitudes up to 2.4 x 10(4) Pa. It is found that as the amplitude of the incident wave is increased, the peak frequency of transmission loss through the two-dimensional trapped-bubble ensemble shifts to lower values by as much as 47%. The experiments indicate that the shifting is caused by the net displacements of air-water-membrane triple-phase lines and the air loss of the trapped bubble, which are due to the radiation force and microbubble production produced by the incident wave. Results of the experiments and possible theoretical explanations are discussed. PMID- 2600313 TI - Finite-amplitude effects on ultrasound beam patterns in attenuating media. AB - Some problems relevant to medical ultrasonics are addressed through experimental measurements of focused, pure-tone beam patterns under quasilinear conditions where significant nonlinearities are manifested. First, measurements in water provide a comparison of the beam patterns of the fundamental and nonlinearly generated harmonics against recent theoretical predictions of others. The radial beamwidths, presence and spacing of sidelobes, axial distances to peak pressures, focal shock parameter, time-domain waveform asymmetry, and post-focal falloff of the fundamental through fifth harmonics are discussed relative to various models under preshock conditions (sigma less than 1). Second, the focused sources are placed in a more attenuating fluid to mimic the behavior of these fields in tissue. The changes in beam characteristics are examined relative to measurements at the same intensities in water, and relative to theoretical predictions. The results suggest that, given a known linear (low-intensity) focused beam pattern in water, guidelines can be followed to predict the beam pattern of the fundamental and higher harmonics at higher intensities in water, and then in attenuating media such as tissue. PMID- 2600314 TI - Determining the extent of coarticulation: effects of experimental design. AB - The purpose of this letter is to explore some reasons for what appear to be conflicting reports regarding the nature and extent of anticipatory coarticulation, in general, and anticipatory lip rounding, in particular. Analyses of labial electromyographic and kinematic data using a minimal-pair paradigm allowed for the differentiation of consonantal and vocalic effects, supporting a frame versus a feature-spreading model of coarticulation. It is believed that the apparent conflicts of previous studies of anticipatory coarticulation might be resolved if experimental design made more use of contrastive minimal pairs and relied less on assumptions about feature specifications of phones. PMID- 2600315 TI - Comments on "Acoustic Transfer Characteristics in Human Middle Ears Studied by a SQUID Magnetometer Method" [J. Acoust. Soc. Am. 82, 1646-1654 (1987)]. AB - The study by Brenkman et al. [J. Acoust. Soc. Am. 82, 1646-1654 (1987)] of malleus umbo and anterior crus of stapes displacement in 14 human temporal bones shows a mean -7.3-dB/oct slope above 1.0 kHz for stapes displacement in response to a 80-dB SPL input at the eardrum. The slope they obtained for midfrequency (1.0-4.0 kHz) stapes displacement is significantly flatter than what was found previously [Gyo et al., Acta Otolaryngol. 103, 87-95 (1987); Gundersen, Prostheses in the Ossicular Chain (University Park, Baltimore, MD, 1971); Kringlebotn and Gundersen, J. Acoust. Soc. Am. 77, 159-164 (1985); Vlaming and Feenstra, Clin. Otolaryngol. 11, 353-363 (1986a)]; in these studies, stapes displacement rolled off at -12.0 to -14.9 dB/oct above 1.0 kHz. It appears that their mean midfrequency stapes displacement slope has been flattened by some unusual results in a small number of ears. Possible reasons for these results are discussed. PMID- 2600316 TI - Dental health and use of dental services by the elderly in Mobile County, Alabama. PMID- 2600317 TI - Dentistry: an art, a science, or a profession? PMID- 2600319 TI - The Dentists Insurance Company: the first ten years. PMID- 2600318 TI - Evaluating dental faculty performance. Perceptions of United States and Canadian dental school faculty. AB - In this study, 342 full-time dental faculty in 67 United States and Canadian Dental Schools ranked, in decreasing order of importance, 12 performance criteria and then ranked the same 12 criteria as they perceived those who evaluate faculty (chairpersons/administration) would rank them. Agreement between faculty's global ranking gave a positive rho of .74. Ranking agreement in 9 of 11 clinical departments were significant and ranged from .58 to .86. Although the global ranking was significant, an important discrepancy in rank-order was noted. Faculty perceived that those who evaluate performance would rank the number of publications number one while faculty ranked classroom, clinical and laboratory teaching number one and the number of publications number six. Implications of the discrepancy between the perceived importance of research productivity and teaching in faculty evaluation were discussed with respect to the increasing emphasis placed on research for dental faculty within the university. PMID- 2600320 TI - Dental students' class attitudes: a four year study. AB - Students in a professional school develop class attitudes that may differ from their individual attitudes and from the educational ideals of faculty. They may be affected positively through the cooperation engendered by the shared attitudes. However, the shared attitudes may be detrimental to student learning. Peer pressure may encourage average performance and unacceptable methods of acquiring information. A survey of class attitudes was designed and administered to the Class of 1988 at Louisiana State University School of Dentistry during each of their four years of training. Percentages of agreement were calculated for each item and chi square analysis was used to compare differences over the four years. Fifty-six students completed the initial administration and 30 of the 50 seniors completed the last administration. The results suggest that although many class attitudes remained stable over the four years, there were some significant changes. The students indicated that as a class they became more likely to take short cuts, to cheat on exams, and to get by with as little effort as possible. As seniors the students showed more positive class attitudes than they had as juniors, but there was a steady deterioration of class attitudes toward the school and faculty over the four years. PMID- 2600321 TI - Penetration of corticosteroids into the lung: evidence for a difference between methylprednisolone and prednisolone. AB - Little is known about the penetration of corticosteroids, such as methylprednisolone and prednisolone, into the lung, despite their common use in the treatment of inflammatory lung diseases. To compare methylprednisolone and prednisolone concentrations in the bronchoalveolar space, we administered these two corticosteroids in a randomized, crossover fashion to 17 adult rabbits. A loading dose was administered and was followed by a continuous infusion for 180 minutes to achieve steady-state plasma concentrations between 200 to 2000 ng/ml. Serial plasma samples were obtained during the infusions. Bronchoalveolar lavages (BAL) were performed at 180 minutes with sterile saline. Plasma and BAL fluid (BALF) were assayed for methylprednisolone and prednisolone concentration by high performance liquid chromatography. Corticosteroid concentrations were normalized to urea concentrations in plasma and BALF. Generally, BALF corticosteroid concentration increased as plasma concentration increased. At plasma concentrations greater than 800 ng/ml, BALF methylprednisolone concentrations increased exponentially, whereas the increase for prednisolone remained linear. BALF methylprednisolone was five times as high as that of prednisolone when plasma corticosteroid concentration was in the 2000 ng/ml range. With this continuous infusion technique, methylprednisolone has a higher degree of bronchoalveolar penetration than prednisolone, and these differences are greater at higher plasma concentrations. PMID- 2600322 TI - The risk of adverse reactions from percutaneous prick-puncture allergen skin testing, venipuncture, and body measurements: data from the second National Health and Nutrition Examination Survey 1976-80 (NHANES II). AB - A sample (N = 16,204) of the U.S. population, 6 to 74 years of age, was examined in NHANES II with a variety of routine medical procedures, including prick puncture allergen skin testing (AST), venipuncture, and body measurements. Eight unstandardized extracts licensed by the Food and Drug Administration, a positive and negative control, were used. AST was performed to screen the population for immediate hypersensitivity responses to common aeroallergens. No anaphylactic reactions after AST were observed. One asthmatic reaction occurred during venipuncture. Other adverse reactions (ARs) were limited to syncope, near syncope, and malaise. The rates for any AR were venipuncture, 0.49% (95% confidence interval [CI], 0.38% to 0.60%); AST, 0.04% (95% CI, 0.01%-0.08%); body measures, 0.006% (95% CI, 0 to 0.018%). Sex or fasting status had little effect on the occurrence of AR. The age group 20 to 49 years had the highest occurrence of any AR to venipuncture (0.87%; 95% CI, 0.633% to 1.107%). The risk of prick puncture AST with eight extracts licensed by the Food and Drug Administration is low and similar to other routine medical procedures. PMID- 2600323 TI - Suppression of immediate skin tests by ranitidine. AB - The suppression of immediate skin reactions to histamine and compound 48/80 by ranitidine, 150 mg every 12 hours for seven doses, was determined in a double blind study in 23 subjects. Ranitidine compared to placebo produced a 22% suppression of the wheal-and-flare response to histamine (p less than 0.05) but only a 4% suppression of the wheal and flare with compound 48/80 (not significant). Although the suppression of the histamine skin test was statistically significant, this degree of suppression may be of limited clinical significance in allergy diagnostic testing. PMID- 2600324 TI - Clinical and immunologic features and subsequent course of patients with severe insect-sting anaphylaxis. AB - One hundred fifty-eight patients were evaluated because of symptoms of potentially fatal venom anaphylaxis, as defined by hypotension, including loss of consciousness (LOC), throat/laryngeal edema, or marked respiratory distress. The demographic characteristics were 118 male and 40 female patients; age range, 3 to 80 years; mean, 29.7 years; 33 patients less than 10 years; and incidence of atopy, 20%. One hundred twenty-seven patients had had prior stings; 27 had prior systemic reactions (SR), including one with LOC. Almost all patients had venom specific IgE; RAST titers covered a wide range. As compared to the total group, the subset of 45 patients with LOC were older, had an increased incidence of cardiac disease and beta-blocker use, stings in the head area, and re-sting reactions in patients who did not receive venom immunotherapy (VIT). One hundred six re-stings occurred in 37 patients receiving VIT with no SR. There were 38 re stings in 18 patients who refused VIT, with 14 SRs in 11 patients. These studies suggest no distinguishing characteristics, including age, that would identify patients susceptible to severe venom anaphylaxis and confirm the prophylactic effectiveness of VIT. PMID- 2600325 TI - Glandular secretion of lactoferrin in a patient with neutrophil lactoferrin deficiency. AB - Patients with specific granule deficiency (SGD) develop recurrent severe bacterial skin infections. Neutrophils from patients with SGD are deficient in lactoferrin (Lf), an antimicrobial protein commonly found in many mucosal secretions. Unstimulated and stimulated nasal secretions, saliva, and tears were collected from a patient with SGD and from normal control subjects and were analyzed for Lf. The secretions from the patient contained normal values of Lf, suggesting that the glands secrete Lf from a source other than neutrophils. Immunohistochemical staining of normal nasal mucosa demonstrated that Lf is localized within serous submucosal gland cells and that neutrophils are not normally observed in the nasal mucosa. These findings suggest that glandular tissues produce and locally secrete Lf by processes that are independent of neutrophil degranulation. PMID- 2600326 TI - Evolution of sensitivity to Hymenoptera venom in 200 allergic patients followed for up to 3 years. AB - Duration of venom immunotherapy still remains questionnable, since some patients outgrow their sensitivity. Two hundred venom-allergic patients (4 to 82 years; mean +/- SD, 37.3 +/- 14.2 years) who were first observed with systemic reactions (SRs) were investigated yearly for up to 3 years. Among these patients, 72 were allergic to honeybee venom, 83 to yellow jacket venom, and 45 to both yellow jacket and Polistes venom. At each visit patients had skin tests and RAST to venom. All patients had the same semirush protocol and a monthly maintenance dose of 200 micrograms. After 1 year of treatment, 19% of bee venom-allergic subjects and 35% of vespid venom-allergic individuals had a negative skin test and RAST to the corresponding venom. The percentage of negativation of tests increased after 3 years to 30.5% in bee venom-allergic patients and to 54% in vespid venom allergic individuals. This rapid and relatively important negativation of skin tests and RAST may be due to a monthly maintenance dose of 200 micrograms; 76 patients experienced a field sting without any SR, two patients had a severe SR, and three patients had a mild SR. Although we tried to define parameters that might predict the abolition of venom sensitivity before starting immunotherapy, we could not find any parameter except venom species. Children and adults behave similarly in terms of evolution of venom sensitization. Mean serum venom-specific IgG levels were significantly lower in patients who had lost their sensitivity. PMID- 2600327 TI - Modification of allergen-induced airway obstruction and airway hyperresponsiveness in an allergic rabbit model by the selective platelet activating factor antagonist, BN 52021. AB - Allergen challenge of eight ragweed-immunized rabbits elicited a prolonged airway obstruction that was evident during the 6-hour study period. Airway responsiveness to histamine was enhanced 24 hours after allergen exposure (geometric mean of the 50% reduction in effective dose [ED50] of dynamic compliance [Cdyn] before challenge, 3.46 mg/ml, decreased to 0.52 mg/ml after challenge, p less than 0.01; pulmonary resistance ED50 geometric mean before challenge, 3.50 mg/ml, decreased to 0.65 mg/ml after challenge, p less than 0.05). In a random crossover study, the selective platelet-activating factor antagonist, BN 52021 (60 mg/kg, orally, 1 hour before allergen challenge), significantly reduced the allergen-induced airway obstruction (p less than 0.005). In addition, pretreatment with BN 52021 reduced the associated increased airway responsiveness induced by allergen exposure (prechallenge Cdyn ED50, 1.93; after challenge, 2.13 mg/ml; pulmonary resistance ED50, 1.91 mg/ml before challenge and 1.69 mg/ml after challenge). These present observations suggest a role for platelet-activating factor in the pathogenesis of allergen-induced airway obstruction and in the development of airway hyperresponsiveness in an allergic rabbit model. PMID- 2600329 TI - Allergy injections administered in physician's office. PMID- 2600330 TI - Postgraduate review course in allergy/immunology. Schaumberg, Illinois, May 4-7, 1989. PMID- 2600328 TI - The Hymenoptera venom study. II: Skin test results and safety of venom skin testing. AB - Data are summarized in this Hymenoptera venom study (HVS) article on the safety of skin testing with venom extracts. Of the 3236 subjects studied, 89% had experienced an historical sting systemic reaction (SSR). Seventy-four percent of all subjects and 76% of subjects who had experienced an historical SSR had a positive skin test to at least one venom. More subjects tested positive to yellow jacket venom (51.8%) than to any other venom. There were no significant differences of the wheal and erythema sizes associated with different venoms or different historical sting reactions. Forty-five percent of subjects with positive venom skin tests (VST) were positive to wasp, and 89% of these subjects were also positive to at least one of the following venoms: yellow jacket, yellow hornet, or white-faced hornet. Sixty-four of the 3236 subjects studied (2%) had a systemic reaction (SR) during VST; 13 of the SRs (0.4%) were severe. Thirteen of 64 adverse reactions (20%) were possibly vasovagal, and six other subjects (9%) demonstrated no symptoms of immediate-type hypersensitivity. Thus, 45 (1.4%) of the 3236 subjects tested had an SR that was considered to be a reaction of hypersensitivity, of which eight reactions (0.25%) were severe. Allergic SRs are associated with VST but are unusual and are rarely severe. PMID- 2600331 TI - Immune mechanisms: T cells and B cells. PMID- 2600332 TI - Immune mechanisms: IgE, complement, and mucosal immunity. PMID- 2600333 TI - Lymphocytes, monocytes, macrophages, and neutrophils. PMID- 2600334 TI - Eosinophils, basophils, and mast cells. PMID- 2600335 TI - Cell-mediated immunity. PMID- 2600336 TI - Laboratory tests. PMID- 2600338 TI - Otitis media, ocular allergy, and sinusitis. PMID- 2600337 TI - Anatomy and physiology of the lower and upper airway. PMID- 2600339 TI - Atopic dermatitis, contact hypersensitivity, and urticaria. PMID- 2600340 TI - Asthma and bronchitis. PMID- 2600341 TI - Allergic and immunologic disorders. PMID- 2600342 TI - Food allergy. PMID- 2600343 TI - Drug allergy and Hymenoptera sensitivity. PMID- 2600344 TI - Immunologic skin diseases. PMID- 2600345 TI - Immunologic disorders. PMID- 2600346 TI - Immunologic disorders of the endocrine system. PMID- 2600347 TI - Allergen immunotherapy and standardization and stability of allergen extracts. PMID- 2600348 TI - Tumor and transplantation immunology. PMID- 2600349 TI - Specific diagnostic modalities: IgE, skin tests, and RAST. PMID- 2600350 TI - Nasal provocation and pulmonary function tests. PMID- 2600351 TI - Aerobiology of pollen and fungal allergens. PMID- 2600352 TI - House dust, animal proteins, pollutants, and environmental controls. PMID- 2600353 TI - 'Could Olympus affect your life?'. AB - In 1989 the European Space Agency will launch the Olympus Communications Satellite, paid for by seven European nations and intended for experiment and demonstration. A number of the facilities will be offered free for a period of up to 5 years in order to stimulate new uses and services. Many of these will be highly technical, but there are several groups who have accepted the challenge with regard to the educational field and are now in the process of hammering out ground rules and creating experimental video material. The ability to interact with material has already changed the approach to devising teaching packages. What does satellite now offer, or not offer, and how might it affect the field of medical education? This paper does not seek to advise, it merely tries to present some 'food for thought'. PMID- 2600354 TI - Training for medical and biological illustration. AB - This paper will discuss the results of a study undertaken in 1986/7 into the education and training of medical artists and designers. It will attempt to identify the skills, knowledge and attitudes which are necessary and desirable for professional practice in the area. PMID- 2600355 TI - Principles of unit charging. AB - Unfortunately, training medical photographers and artists does not include finance management, but in the 'cost effective' atmosphere of both NHS and universities today we must learn to approach the subject in a manner likely to satisfy our financial masters. The experience gained in introducing a unit cost system and using it for 17 years will be reviewed but more importantly, as the system has been adopted and adapted by so many, the benefits of using such a system and changing to concur with current financial thinking will also be discussed. Are we in such a Korner as we might think? PMID- 2600356 TI - St Bartholomew's resources allocation scheme. AB - This scheme has three main features: it relates the output of work and materials from the department to the funding input (resource allocation), it enables the funding bodies to determine the level of output they are willing to support and it creates spare capacity to permit income generation either through charging for work done in excess of allocations made under the scheme or by attracting outside business. The system devolves upon the work unit as a measure of resource and this is made up of a combination of materials and time depending on the product. Derivation of work unit cost is given as a function of all reckonable operating costs of the department. Different profit margins may be applied according to category of request. Income is returnable to the funding bodies in the same ratio as their original provision to the service (for the current year of operation) after a deduction for reinvestment. The scheme allows for central funding to be progressively reduced to zero. PMID- 2600357 TI - Profit making in medical illustration. AB - 'Cost recovery' is the name of the game these days. However, cost recovery is not the only way to improve funding. The aim of this paper is to show how a free service can still be maintained by better utilization of the professional skills available in medical illustration departments. All medical departments should have skills which are unique to medical illustration. These are skills which are marketable but which, in many cases, are being grossly undersold. If their full potential is realized many more departments would find themselves in a far healthier state than they are at present. PMID- 2600358 TI - Cost recovery and its effects on the profession. AB - More departments are having to implement a cost recovery service and also market their skills in the commercial sector. Less time is becoming available to devote to professional matters. What will be the long-term effects on the professional progress of medical illustration if this is allowed to continue? PMID- 2600359 TI - Financing medical illustration in the academic environment. AB - Government policy is now exposing hospitals and universities to so-called free market forces, where success or failure will hold the key to their future. If medical illustration departments are to continue to provide a viable service under the proposed plans then a radical restructuring of their position within each organization will have to be considered. The answer could lie in going beyond the existing cost recovery methods and opting out completely from the clutches of government funding, i.e. setting up departments as private companies. PMID- 2600360 TI - Fundamentals of video production and script writing. AB - Designing and producing videos for medical teaching has nothing in common with television production for broadcasting. The educational video producer has a well defined audience of known intellectual level, the audience is small and the justifiable budget commensurate. The producer must capitalize on the presentational characteristics of the television medium and ensure that the video fits the learning context. The production process is explained with the different roles and responsibilities emphasized. PMID- 2600361 TI - The living anatomy of the knee. AB - A brief account is given of the subject chosen by a candidate for the IMBI Higher Examination. His major project was to produce a video programme about the knee. With limited technical equipment at his disposal, but with plenty of visual imagination and technical ingenuity, a programme was produced that not only gave him a distinction award in his examination, but also received wide acclaim and won him several awards. PMID- 2600362 TI - Toxicological assessment of chlorinated diphenyl ethers in the rat. AB - Chlorinated diphenyl ethers are environmental contaminants that have been found in Great Lakes fish and birds. Because of their presence in the food chain, and potential for human exposure, the present short-term study was conducted to assess their toxicity. Groups of 10 male and 10 female rats were each given by gavage 2,2',4,4'6-pentachlorodiphenyl ether (CDE1), 2,2',4,4',5,6 hexachlorodiphenyl ether (CDE2) or 2,2',3,3',4,6'-hexachlorodiphenyl ether (CDE3) at dose levels of 0.04, 0.4, 4.0 or 40 mg/kg b.w./day for a period of 28 days. The control group received an equivalent volume of corn oil only (0.5 ml/100 g b.w.). Treatment with the three CDE congeners did not result in suppression of growth rate or food consumption. Increased liver weights were seen in the animals of both sexes fed 40 mg/kg CDE2, in males treated with 40 mg/kg CDE1, and in females with 40 mg/kg CDE3. Hepatic microsomal aminopyrine demethylase activity was significantly higher in the male rats administered 40 mg/kg CDE2, and aniline hydroxylase activity was elevated in the females following the same treatment. Serum glucose, calcium, protein and urea nitrogen of CDE1-treated males were higher than the control. Levels of uric acid, potassium and LDH of CDE3-treated females were also elevated. No hematological changes were observed. Histological examination revealed that the liver and thyroid were the target organs affected by CDE treatment but the morphological changes were mild even at the highest dose level. Changes in the liver consisted of nuclear vesiculation and increased cytoplasmic volume. Alterations in the thyroid were characterized by increased epithelial height and follicular collapse. Based on the data presented above, the 3 CDE congeners can only be considered moderately toxic in the rat. PMID- 2600363 TI - Inhibitory pattern of tissue esterases in rats fed dietary pirimiphos-methyl. AB - Activities of Acetylcholinesterase (AChE) in brain and erythrocytes, pseudocholinesterase (PChE) in plasma and non-specific carboxylesterase (NSE) in brain, liver, plasma and kidney were assayed at weekly intervals in growing male rats fed dietary pirimiphos-methyl at dosages of 1000, and 1500 ppm for a period of 28 days. Significant inhibition of tissue esterases were observed at the end of 7 days at both the dosages and the enzyme activities remained markedly inhibited at subsequent intervals. Activities of all enzymes (excepting Brain AChE) returned to normal levels following a 7-day maintenance on the insecticide free diet implicating that pirimiphos-methyl induced little or no permanent tissue damage. The results suggest that plasma NSE level may also serve as a sensitive indicator in monitoring OPI exposure. PMID- 2600364 TI - Heavy metal tolerance of rice plants (Oryza sativa L.) to some metal oxides at the critical levels. AB - The toxicity of metal oxides (CdO, ZnO, PbO) were compared with each other and the critical levels of metal uptake by rice plants were determined. The order of metal toxicity to rice plants is CdO greater than ZnO greater than PbO. The highest concentration obtained for unpolished rice was 4.97 micrograms/g at the Cd 10,000 ppm in soil. This values is higher than every other we have seen in the reports for treatment with CdO. We are able to find out that the concentration of 10,000 ppm Cd in the form of CdO in the critical one towards rice plant. By contrast, such damage was not observed at even higher levels of ZnO and PbO were considered to have low toxicity toward rice plant. Also, a negative correlation between Zn or Cu accumulation in rice plants and Cd concentration in soil was found. PMID- 2600365 TI - Do nurses consistently document incontinence? AB - 1. Urinary incontinence is inconsistently documented on medical records of nursing home residents. 2. Documentation of urinary incontinence by professional nurses may be improved by changes in organizational factors such as staffing, policy implementation, and staff education. 3. Forms that employ cue words for eliminative status show more documentation of continence status than forms that have an open format. 4. Evaluation of changes in nursing practice in the nursing home setting can benefit from nursing studies that employ an organizational perspective. PMID- 2600366 TI - Nutritional assessment of the elderly. AB - 1. The elderly often have a declining ability to absorb and utilize nutrients, and they frequently take medications that interfere with the body's use of nutrients. 2. Nutritional assessment involves history taking (medical, social, and psychological) and physical examination with physical measurements and analysis of laboratory data. 3. The most frequently used indicators of nutritional risk or depletion are those obtained by nurses in direct contact with patients. 4. Nurses tended to rely more on intuitive data than on laboratory values, upper arm circumference, or skinfold thickness. PMID- 2600367 TI - How to diagnose and treat chemical dependency in the elderly. AB - 1. It is difficult to assess what percentage of the older population is chemically dependent; available literature cites between 2% and 70% of adults over age 60 have illnesses or other serious consequences as a result of alcohol abuse. 2. It is often difficult to differentiate between the signs and symptoms of chemical dependency and other physical, emotional, and social changes that occur with aging. 3. Chemical dependency often goes unrecognized in the older adult because of poor assessment skills and tools available to health-care professionals. 4. Once identified and treated, the recovery rate of the older adult alcoholic is equal to that of the younger alcoholic; however, there are specific treatment needs unique to the older adult that must be recognized and addressed in rehabilitation programs. PMID- 2600368 TI - When deaf people become elderly--counteracting a lifetime of difficulties. AB - 1. Deaf people may feel like foreigners, alone and unable to relate with those in their environment. This is due to the lack of integration with and different enculturation than hearing persons. 2. Deaf individuals raised by hearing parents who cannot communicate with them may develop feelings of powerlessness and frustration. These feelings develop into doubt and distrust of all hearing people. 3. Deaf people feel more handicapped by hearing people's negative attitudes than by hearing loss itself. The elderly deaf people who perceive negative and discriminatory attitudes from hearing caregivers might be uncooperative or resentful. 4. The handicap of being deaf has a disabling effect beyond the hearing impairment and compound the effects of aging. PMID- 2600369 TI - Older women: a challenge to gerontological nursing. PMID- 2600370 TI - The root of it all--genograms as a nursing assessment tool. AB - 1. The genogram is a tool that can be used by nurses to provide a comprehensive, holistic picture of the elderly client and his environment. A genogram can serve both as an assessment tool and as an intervention strategy. 2. Information gathered through a genogram can be classified as demographic, functional status/resources, and critical events/dynamic changes. 3. The ability of the elderly client to actively participate in the genogram process gives assessment data about the client's functioning in sensoriperception, memory, functional communication, fine motor skills, and behavioral domains. 4. The genogram provides a highly organized and easily visualized method of gathering, displaying, and communicating information to the elderly client and to other health-care professionals. PMID- 2600371 TI - As young as you feel: age identification among the elderly. AB - 1. Understanding and integrating an individual's perceptions about age and health status is fundamental to making accurate assessments and implementing interventions that are personally acceptable and clinically appropriate. 2. The concept of chronological age has limited validity for the explanation of behavior because it wrongly assumes homogeneity in individual lifestyles among age cohorts. 3. Older adults tend to perceive themselves as mentally and physically younger than their chronological age. 4. Nurses who interact with individuals in a manner based solely on their chronological age may exhibit disrespect and underestimate the potential for the client's involvement in self-care activities. PMID- 2600372 TI - [Risk factors for condylomata. A case control study]. AB - The present study involves 214 patients whose cervical smear showed signs of human papilloma virus infection (HPV), matched with 1042 controls. We demonstrate increasing odds ratio with the total number of sexual partners since first sexual intercourse (p less than 0.0001). Moreover the cases have more often changed partners in the year preceding the diagnosis (odds ratio 2.6 p less than 0.0001). Their male partners more often have occupations that expose them to "extra conjugal adventures" (p = 0.0005). Using a logistic regression analysis we demonstrate the independence of the masculine and feminine risk factors. After adjustment for age, reason for consulting and marital status the following factors are related to HPV infection: new partner, total number of sexual partners since first sexual intercourse and partner's occupation. PMID- 2600373 TI - [Epidemiology of gyneco-obstetric emergencies (within the framework of emergency medical care)]. AB - The authors studied over a period of four years emergencies in pregnancy. These were seen in patients who were brought in from an outside hospital to a perinatal centre or when transferred from hospitals to a general maternity unit or to a high risk unit for neonatal and maternity care. 382 pregnant women needed to be looked after (293 from outside hospital and 89 transferred from another hospital). Treatment was given especially in the 3rd trimester of the pregnancy to three groups: before labour (60 cases); during labour (211 cases) and; after delivery (30 cases). There were in the same categories 37 cases before labour, 9 cases during labour and 30 cases after labour transferred from one hospital to another. The diagnosis were, in particular, 47 cases with a high risk of premature labour, 5 cases with haemorrhage and placenta praevia, 27 cases of pre eclampsia, 211 cases in labour of which 120 were outside hospital. There were 14 cases of maternal illness, 3 cases of trauma and 4 cases of cardiac arrest. There was a high risk of prematurity in 33 cases of labour outside a maternity hospital. The neonatal mortality rate for the first six days after delivery was ten times higher than that for all neonates born in the same county in the same period of time as this series took. But the authors noted that pre-eclampsia cases received care at high risk units but premature cases did not necessarily. PMID- 2600374 TI - [Extra-uterine pregnancy. Study of 509 cases surgically treated at the University Hospital Center of Libreville]. AB - Extra-uterine pregnancy is the principal emergency procedure undertaken in the University Department of Libreville. We study 509 cases treated surgically between 1984 and 1987, which is a level of 16/1,000 deliveries. The incidence of rupture of the tube has driven us to search for the best possible means to diagnose the condition earlier. Ultrasound gives the best results, dropping the level of ruptured tubes from 83% in 1984 to 50% in 1987. Extra-uterine pregnancy in nulliparous patients (25% of the group) presented a third of recurrent ectopics. The anatomopathological examination of the tissues emphasizes how common acute or chronic infections of the tubes are (25%) and salpingitis isthmica nodosa (31% of cases). If sexually transmitted diseases can be prevented the incidence of ectopic pregnancies will drop. We have tried since 1986 to be conservative in our surgery hoping that a secondary plastic operation will improve the fertility of these young patients. Mortality was high (13.75/1,000 ectopics). The principal factor responsible for this high figure is the absence of blood transfusion banks which delayed resuscitation and exposed the patients to the risk of coagulation defects when surgery is practised on these patients who are still shocked. PMID- 2600375 TI - [Role of karyotype in studying male infertility]. AB - The karyotype of 443 infertile males has been studied (infertility of unknown etiology). The sample has been divided in 3 groups according to the data of their spermogram: Gr 1--101 males with a normal spermogramm (selected through the sterility of their couple). Gr 2--185 infertile males with oligospermy (less than 20 millions spermatozoal/ml). Gr 3--157 infertile males with azoospermia. This study shows: --No significant difference in chromosomal aberration rate between group 1 and general male population. --A rate of 5% chromosomal aberration in group 2 (versus 0.7% in normal male population p less than or equal to 10(-8], nearly exclusively balanced translocations. --A rate of 21% chromosomal aberration in group 3, nearly exclusively 47, XXY or 46, XX (p less than or equal to -9). The karyotype is unlikely to bring any information in infertile males with normal spermogram; on the contrary it is of valuable interest in infertile males with abnormal sperm. PMID- 2600376 TI - [Correlation of the penetration test of zona-free hamster ovocytes and other sperm parameters. Value of this test in evaluating male infertility]. AB - On investigating infertility in 162 couples the zona-free hamster egg penetration test was carried out. As a control we tested the ejaculates of 34 fertile men. There is a significant correlation between the percentage of oocytes that were penetrated and the count (p less than 0.001) in motility after one hour (p less than 0.001) and the count after migration (p less than 0.001). The outcome in 129 infertile couples made it possible for us to confirm that the percentage of oocytes penetrated, the initial motility and the number of motile sperms after migration are the best parameters for assessing sperm function that are known (p much less than 0.001) for investigating male fertility. Finally a study of the test in fertile sperm donors made it possible for us to raise statistically significantly the numbers of pregnancies per artificial insemination cycle when the percentage of oocytes penetrated is higher than 50% (p much less than 0.001). Although the egg penetration test did not prove male sterility it can be considered an extra test to be carried out over and above the sperm count and post-coital test in evaluating the fertilisation capacity of sperm. PMID- 2600377 TI - [Accessory spleen on the left ovary. Discussion on its pathogenesis]. AB - The authors report a case of an accessory spleen attached to the left ovary, discovered in a hysterectomy and bilateral adnexectomy specimen obtained for leiomyoma. This is an exceptional congenital anomaly as only seven cases have been reported in the medical literature. It may be classified as a type of spleno gonadal fusion. It is always localized to the left side. This anomaly may be manifest as an inguinal tumefaction or by an intestinal occlusion requiring exploratory laparotomy. It is caused by fusion of the spleen to the left urogenital bud during the 5th to 8th weeks of fetal development. PMID- 2600378 TI - [Analysis of 42 membrane ruptures during the second pregnancy trimester]. AB - 65 cases of premature rupture of the membranes before the 28th week of amenorrhoea occurred during the 5 years between 1983 and 1987 in two maternity units in Paris. A retrospective study was carried out on 42 of these cases where conservative measures had been decided on. In two-thirds of the cases, of which 42% had had bleeding and 40% vaginal infection, the pregnancy had appeared to be progressing normally before the rupture of the membranes. 14% had had cerclage and 12% had had selective intrauterine fetal reduction or biopsy of the trophoblast or removal of an intrauterine device. Rupture of the membranes rarely happens in isolation because it is usually accompanied by uterine contraction or bleeding, which may occur separately or associated with one another in half the cases. In 21% of cases bacteriological examination was positive after the rupture. All patients were treated conservatively in this study. Antibiotics were prescribed in 35 cases and tocolysis in 13 cases. The membranes were ruptured on an average for 7 days. It was almost impossible to avoid infection except in two patients who delivered rapidly. The pregnancies resulted in 8 intrauterine deaths, 15 deliveries of babies that were not viable, 19 deliveries of live babies of which 7 were by caesarean section. 15 babies survived the neonatal period. This work makes it possible to judge whether it is really hazardous to try to be conservative before the 24th week of amenorrhea. Even if neonatal mortality is being lowered at term, overall in our series it was 25%. Finally, it does not seen that tocolytics or antibiotics help to lower this mortality significantly. PMID- 2600379 TI - [Forceps at a university hospital. Critical study of the evolution of the procedure]. AB - A retrospective study was carried out using the obstetric summaries in a computer between the years 1981 and 1986. The percentage of instrumental deliveries using forceps or spatula was significantly reduced whereas the caesarean section rate stayed the same: the majority of forceps deliveries during the year 1986 (14.5% of all deliveries) were carried out under epidural analgesia (70% of the deliveries) and the mean of these (75%) were carried out for delay. This is a definite change as compared with 1981 and it appears to be linked mainly to an increase in the number of epidural analgesics (70% for forceps deliveries in 1986) and a new appreciation of fetal distress. The maternal results were better because most episiotomies were lateral (60% of cases) which meant that only 1.5% of cases affected the sphincters. The immediate neonatal results were good, but do not seem to have been improved by the changes that have been observed, although the methodology for assessing the state of the neonate has improved. PMID- 2600380 TI - [Treatment of urinary infections in pregnant women]. PMID- 2600381 TI - [Apropos of a simple technic of colposuspension]. PMID- 2600382 TI - Socioeconomic, medical care, and public health contexts affecting infant mortality: a study of community-level differentials in Peru. AB - Socioeconomic, medical care, and public health contexts are examined in Peruvian communities for their relationship to infant mortality. A deviant case analysis is used to uncover characteristics important in the social structure of Peruvian communities. Results from fieldwork in two "deviant" communities suggest that economic diversity, income disparity, social class fluidity, and women's autonomy, along with refined measures of medical care and public health resources, are important in understanding differentials in mortality. Attention is drawn to the community context and to the interplay of socioeconomic determinants affecting infant mortality. PMID- 2600383 TI - Access to health care in urban areas of developing societies. AB - Emphasis on rural health problems has led to a relative neglect of urban health issues in developing societies. Yet the fact that a large proportion of the limited financial and human resources is allocated to urban health care makes it imperative for researchers and health planners to evaluate the effectiveness of the urban health care system. This paper examines data on health care utilization from a sample survey of 1500 households conducted in three areas of Accra, Ghana in 1982. The factors that influence the use of three types of health care services (clinics, drug vendors, and traditional healers) are examined. Suggestions are made for increasing the effectiveness of the health care system in Accra, with the aim of making medical care more accessible to all families. PMID- 2600384 TI - Modern health services and health care behavior: a survey in Kathmandu, Nepal. AB - The most important problem regarding health service utilization in Third World countries is that established indigenous forms of health care are readily available and compete with modern health care. Thus, in addition to understanding the components of the decision to seek medical help, we must understand the conditions that affect the choice of a specific health care system. This study examines the impact of medical pluralism on the use of modern forms of health care in Nepal. The findings show that the presence of medical pluralism is a significant factor which delays use of modern health services. Policy implications are discussed, and the need for more research in this area is stressed. PMID- 2600385 TI - Malaria treatment practices among mothers in Guinea. AB - A survey of mothers of young children in Guinea, West Africa (June-July 1988) suggests that individual, sociocultural, and structural factors influence the use of antimalarials for episodes of fever presumed to be malaria. A survey of 243 mothers was carried out in eight different sites (four urban and four rural) in two regions of the country. Among mothers interviewed, use of Western antimalarials for infants and children with fever was acceptable, but access to treatment was problematic. Mothers interviewed were less likely to use antimalarials during pregnancy, partly because of certain misconceptions about their effects and lack of access to the medication. Despite programmatic efforts to promote practices of presumptive treatment of fever among young children and chemoprophylaxis during pregnancy among mothers in towns and villages surveyed, variables associated with low use of antimalarials by mothers and their young children reflect important barriers to the implementation of child survival initiatives. PMID- 2600386 TI - Changing the structure of medical discourse: implications of cross-national comparisons. AB - In the discourse of medical encounters, social problems arise frequently. Such problems typically derive from work and economic insecurity, family life and gender roles, aging, and conditions that foster substance use or other self destructive behavior. The structure of medical discourse tends to marginalize the social issues that generate personal troubles in everyday life. Long-range strategies to alter medical discourse aim toward basic modifications of power and finance in the larger society of which medicine is a part; such strategies seek to change the contextual issues that create personal troubles on the individual level. As shown by the examples of the Soviet Union, eastern Europe, and China, social revolution does not necessarily resolve the micro-level contradictions of the doctor-patient relationship. In contrast, the Cuban revolution apparently has succeeded in transforming both the context and the structure of medical encounters. Short-range strategies in countries such as the United States involve more direct ways in which patients and doctors can alter their communication. These alterations involve reducing devices of language that maintain professional dominance, avoiding the medicalization of nonmedical problems, attempting not to marginalize contextual issues, and encouraging active attempts to change social conditions that generate personal troubles. PMID- 2600387 TI - The emergence of a health insurance system in a developing country: the case of South Korea. AB - In an attempt to understand the social forces and the economic and political conditions under which new social policies emerge in developing countries, this study outlines factors affecting the introduction of the health insurance system in South Korea. The emergence of the South Korean health insurance system was influenced by changing labor needs of the industrial sector, increasing social expectations, external and international pressures, increasing medical costs, and class conflict. These pressures compelled the South Korean government to respond to demands for the introduction of new social welfare policies in the 1970s. In the case of South Korea, the new health insurance system resulted from the government's attempts to cope with political, economic, and social pressures rather than from an ideological commitment to the well-being of the population. The resulting insurance system was a way to maintain the social order and legitimacy of the regime, and a means to promote the health of groups important to defense or production. PMID- 2600388 TI - Emergency medicine magnifying loupes. AB - A magnifying loupe system has been evaluated for use in emergency medicine. Physicians uniformly preferred a Keplerian lens system over that of the Galilean lens system. The advantages of the Keplerian lens were its increased field of view and its brighter and clearer peripheral image. The Keplerian loupes allowed the physician to visualize the exquisite details of wound configuration and to perform wound closure using microsurgical techniques. PMID- 2600389 TI - A clinical evaluation of the QBCII centrifugal hematology analyzer in the emergency department. AB - As part of an effort to reduce patient waiting time for laboratory results, the QBCII desktop CBC analyzer was evaluated in an emergency department. CBCs were performed by the emergency department staff (multiple observers) on 498 patients and by a single observer on 250 patients. Time required by the emergency department staff to obtain a CBC was 10.1 minutes compared with 47.8 minutes for the hospital laboratory. Correlation coefficients between hospital laboratory and QBCII were WBC 0.94, hematocrit 0.92, platelets 0.88, lymphocytes/monocytes 0.92, and granulocytes 0.90. PMID- 2600390 TI - Lack of tachycardic response to hypotension in penetrating abdominal injuries. AB - Vital signs upon arrival to the emergency department were studied retrospectively in 59 consecutive patients with isolated penetrating abdominal injuries to determine their chronotropic response to hypotension. Forty-three patients with documented intraperitoneal injury were included in the study and separated into hypotensive and normotensive groups using a systolic blood pressure of 90 or 100 mm Hg. The difference in mean pulse rates between normotensive and hypotensive groups was not statistically significant (P greater than 0.05) although a wide range of pulse rates was noted in both groups. Nearly half of all hypotensive patients were not tachycardic, defined as a pulse rate less than 100. Similar findings were observed when the 117 sets of vital signs recorded both in the field and in the emergency department were analyzed as independent pieces of data. Several mechanisms are proposed for the lack of tachycardia in the presence of hypotension. This data suggest that tachycardia may not be a reliable sign of hypovolemic shock when defined by blood pressure criteria in these patients. PMID- 2600391 TI - Aortoenteric fistula without aortic dilatation: case report. PMID- 2600392 TI - Acute compartment syndrome following a minor athletic injury. AB - An athletic young male presented with right calf pain following a twisting injury during a soccer game. Other than apparently severe calf pain, no symptoms or signs of compartment syndrome were noted. The patient later returned with lateral and anterior compartment syndrome, and suffered partial loss of peroneal nerve and muscle function despite fasciotomy. Although rare, acute compartment syndrome resulting from seemingly minor injury or exertion has been reported. Pain out of proportion to the apparent injury and a history of chronic leg pain with exertion may be helpful in identifying these patients prior to development of more obvious signs and symptoms. The diagnosis of acute compartment syndrome may be confirmed by compartmental pressure measurement. Prompt intervention is indicated once the diagnosis is established. PMID- 2600393 TI - Movement disorders as a manifestation of nonketotic hyperglycemia. AB - Movement disorders are well-known presenting signs of metabolic disorders. Focal motor abnormalities may be the chief initial presentation of diabetes mellitus in the nonketotic hyperglycemic state in 6% of patients. Nonketotic hyperglycemia (NKH), in particular, may manifest any of a wide variety of movement disorders. These have been described as focal seizures, epilepsia partialis continua, myoclonus, and opsoclonia. There are descriptions of movement disorders in hyperglycemia that are similar to the coarse flapping tremor of asterixis, the posturing of paroxysmal kinetogenic choreoathetosis, and of "fencing (stance) seizures." Disorders of facial motor function including aphasia, facial muscle twitching and jerking, and disorders of muscular tone have been described. These may include hemiparesis and hemiplegias as well as increased tone, in some cases mimicking the nuchal rigidity of meningitis. The movement disorders in NKH may mimic cerebral vascular accidents, meningitis, or psychiatric disorders, as well as various types of seizures. Clinicians may be able to avoid expensive and time consuming diagnostic evaluations to rule out NKH in patients with movement disorders. We present two patients with focal motor abnormalities associated with nonketonic hyperglycemia and review the pertinent literature. PMID- 2600394 TI - CT evolution of an acute venous epidural hematoma. AB - Acute traumatic epidural hematoma may develop secondary to an arterial or venous bleed. The computed tomography (CT scan) appearance of the hematoma depends on the source and severity of bleeding, the interval between injury and CT scan, and the degree of clot organization or breakdown. We report the emergency evaluation, CT scan evolution, and clinical management of one such acute venous epidural hematoma. PMID- 2600395 TI - Recovery of cyclic antidepressants with gastric lavage. AB - The role of lavage fluid volume in recovery of cyclic antidepressant with gastric lavage was determined in 13 patients treated for moderate to severe cyclic antidepressant intoxication. An orogastric tube was placed, gastric contents aspirated, and gastric lavage performed with 60 to 180 mL aliquots of tap water or 0.9% NaCl for irrigation. A volume of 12.8 +/- 4.4 liters of lavage fluid was instilled, and 97.6 +/- 6.9% of this volume was recovered. The recovered aspirate and lavage fluid were inspected for the presence of particulate matter and saved in 4 to 5 liter collections. Determination of cyclic antidepressant and metabolite concentrations was performed using gas chromatography-mass spectrometry, and the amount of cyclic antidepressant recovered was calculated. The mean total amount recovered was 110 mg and ranged from 2.4 mg to 342 mg. Of the total amount recovered, 88% +/- 13% was recovered in the first 4 to 5 liters of lavage fluid. An estimate of the dose ingested was available in 7 patients, with 8.7% (0.4% to 21.7%) of the estimated dose recovered by lavage. There were no cases of significant drug recovery in clear lavage fluid. We conclude that if gastric lavage is undertaken in cyclic antidepressant intoxications, it should utilize 5 liters initially and then continue only if particulate matter is seen. PMID- 2600396 TI - Effect of crowd size on patient volume at a large, multipurpose, indoor stadium. AB - A prediction of patient volume expected at "mass gatherings" is desirable in order to provide optimal on-site emergency medical care. While several methods of predicting patient loads have been suggested, a reliable technique has not been established. This study examines the frequency of medical emergencies at the Syracuse University Carrier Dome, a 50,500-seat indoor stadium. Patient volume and level of care at collegiate basketball and football games as well as rock concerts, over a 7-year period were examined and tabulated. This information was analyzed using simple regression and nonparametric statistical methods to determine level of correlation between crowd size and patient volume. These analyses demonstrated no statistically significant increase in patient volume for increasing crowd size for basketball and football events. There was a small but statistically significant increase in patient volume for increasing crowd size for concerts. A comparison of similar crowd size for each of the three events showed that patient frequency is greatest for concerts and smallest for basketball. The study suggests that crowd size alone has only a minor influence on patient volume at any given event. Structuring medical services based solely on expected crowd size and not considering other influences such as event type and duration may give poor results. PMID- 2600397 TI - Cervical spine immobilization with axial traction: a practice to be discouraged. PMID- 2600398 TI - Therapeutic legends of emergency medicine. PMID- 2600399 TI - Forearm and wrist radiology--Part I. AB - The emergency physician must be well versed in diagnosing forearm and wrist injuries. Although many of these injuries are readily apparent, others require more sophistication to appreciate. Careful attention to radiographic findings given the assistance of a well-directed history and physical examination is imperative. Both the more common and the more subtle injuries are discussed. PMID- 2600400 TI - Emergency department stat laboratory: a solution or a problem. PMID- 2600401 TI - Gastric lavage and acute poisoning. PMID- 2600402 TI - Emergency physicians and special events. PMID- 2600403 TI - Treatment of accidental epinephrine injection in a finger. PMID- 2600404 TI - In response to Dr. Ratzan. PMID- 2600405 TI - Observations on hemotympanum. PMID- 2600406 TI - Questions on diazepam-induced dystonia. PMID- 2600409 TI - Carbon monoxide poisoning during the summer in an air-conditioned vehicle: a case report. PMID- 2600408 TI - A new course for emergency physicians. PMID- 2600407 TI - Further query on dystonia. PMID- 2600410 TI - Differentiation between Trichinella spiralis and T. pseudospiralis infective larvae by a monoclonal antibody. AB - Crude saline extracts of Trichinella spiralis and T. pseudospiralis infective larvae were studied by Western blot analysis using a monoclonal antibody, named ES/TA2 and produced against T. spiralis larvae. This monoclonal antibody recognized seven major antigenic components in T. spiralis larvae with apparent Mr: 45, 48, 50, 68, 70, 92 and 105 kDa and five in T. pseudospiralis larvae: 38, 50, 70, 72 and 92 kDa. SDS-PAGE of both extracts did not reveal appreciable differences in the range of molecular weights recognized by ES/TA2. These facts show the existence of immunological differences among proteins with apparently identical molecular weights. PMID- 2600411 TI - Lipid metabolism in Trichuris globulosa (Nematoda). AB - Adult males and females of Trichuris globulosa, an intestinal nematode parasite of goats, were studied for their lipid composition, capability of incorporation of (Na)-1-14C-acetate into different lipid classes and the activity of certain key enzymes of lipid metabolism. The parasite possesses a large variety of lipids including certain complex lipids. These are phosphatidylcholine (PC), diphosphatidylglycerol (cardiolipin), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), phosphatidylserine (PS), phosphatidylinositol (PI), plasmalogens (choline + ethanolamine), mono-, di- and triacylglycerols, free and esterified cholesterol, non-esterified fatty acids (NEFA), gangliosides, cerebrosides (glycosyl ceramide) and sulphuric acid esters of cerebrosides (sulphatides). The females contain more lipids than males, particularly the acylglycerols and phospholipids, possibly to meet the energy requirement and structural entities for the daily production of large numbers of eggs. Incorporation studies of labelled substrate, sodium-1-14C acetate demonstrate that the adult female has extremely active mechanisms for biosynthesizing these lipids. Most of the labels are found in PC, PE, SM, acylglycerols, NEFA, gangliosides, cerebrosides and sulphatides. Cholesterol, although a minor component of the parasitic lipids, incorporates large amount of label and also undergoes fast turnover. Kinetic analysis of the incorporation by measuring the rate constant (k) and half life (t1/2) reveals that gangliosides are the fastest biosynthesizing and turning over lipids, although they constitute only 0.1% of the total lipids. The presence of important enzymes of lipid biosynthesis, glucose-6-phosphate dehydrogenase, malate dehydrogenase and hydroxymethyl glutaryl-CoA reductase and an enzyme of lipid ester hydrolysis, triacylglycerol lipase, is also established in T. globulosa. Michaelis-Menten kinetic characteristics of the parasitic enzymes (Km, Vmax, v and the first order rate constant, k) are comparable with those of rat liver homogenates. PMID- 2600412 TI - Muellerius capillaris in north-east Zaire: prevalence in sheep and goats and determination of intermediate hosts. AB - Muellerius capillaris was the only species of nematode recovered from the lungs of young and adult sheep and goats of north-east Zaire. The prevalences were of 19% (sheep) and 32% (goats). The slug Atoxon pallens contained larvae in natural conditions and represents a potential intermediate host. The land snails Achatinidae (Achatina stuhlmanni and Limicolaria spp.) could not be experimentally infected with M. capillaris larvae. PMID- 2600413 TI - Dissociation of the protective immune response in the mouse to Strongyloides ratti. AB - The generation of protective immunity by various stages in the life-cycle of Strongyloides ratti and the phases against which resistance is directed has been examined in murine strongyloidiasis. Mice were exposed to natural, complete infections, were treated with thiabendazole (which largely resembles the natural infection), were treated with cambendazole (which restricts infection to the larval stage), or infected directly by oral transfer of adult worms. Mice that were infected with infective larvae alone did not become resistant to infective larvae or the complete infection but were resistant to adult worms implanted directly into the gut. Mice exposed to adult worms alone were resistant to natural infections and adults worms implanted directly but were not resistant to infective larvae. On the other hand, mice that had received prior natural infections showed evidence of resistance to infective larvae, adult worms, and natural, complete infections. It is concluded that there is immunological cross reactivity between infective larvae and adult worms but that under certain circumstances the infective larvae are able to evade the host's protective immune response. PMID- 2600414 TI - Further studies on the effect of cyclosporin A on the course of Paragonimus infection in rats. AB - Paragonimus ohirai-infected rats were treated with cyclosporin A (CyA) at different times during the course of infection. CyA (5 x 80 mg/kg) affected the worm recovery, growth and maturation rates of P. ohirai with respect to control values. This tendency was most remarkable in animals treated 15 days and more after infection with CyA (groups B, +15 to +19 days; C, +25 to +29; D, +35 to +39 and E, +45 to +49). In group A (0 to +4), however, the drug did not affect markedly the growth and maturation of worms, although it significantly lowered worm recovery rates. CyA administration also affected normal migration of P. ohirai in the highly susceptible host (rat), when the drug was administered during the peritoneal and/or liver phase of infection. Thus, in this P. ohirai/rat model, CyA significantly reduced worm recovery rates, and affected the growth, maturation and migration of the worms depending on the time of administration. PMID- 2600415 TI - Rapid recovery of Echinococcus granulosus following 'successful' albendazole therapy in a gerbil model. AB - Peritoneal Echinococcus granulosus in gerbils was treated with albendazole. Both early and late infections were studied; response to albendazole therapy and the ability of the parasite to recover after treatment was found to depend on dose and length of therapy. Even after treatment at 50 mg/kg for 2 months late infections retained the ability to recover over 3 months. PMID- 2600416 TI - Chest mass in an 11-year-old. PMID- 2600417 TI - Fresh frozen plasma: past, present and future. AB - Fresh frozen plasma has been transfused for decades. However, the dramatic increase in its use has caused concern that much of it is transfused without the proper indications. Because of this, the National Institutes of Health held a Consensus Conference to clarify its genuine indications and contraindications. PMID- 2600418 TI - Letter serves as inspiration to physicians. PMID- 2600419 TI - Capitation complications--contracts--coercion. PMID- 2600420 TI - Fluoride in our drinking water--analysis and supplementation. PMID- 2600421 TI - Child abuse and neglect: know the law. PMID- 2600422 TI - A simplified test for interdental gingival inflammation. PMID- 2600423 TI - AIDS education and training centers for Texas and Oklahoma. PMID- 2600424 TI - Preparation of diazotized polystyrene latex and its use in agglutination assays. AB - The preparation of this immunological latex consisted of the following steps: the synthesis of polystyrene, polynitrostyrene, polyaminostyrene and polystyrene diazonium salt latex. The quantities of emulsifier and initiator used in the synthesis of the polystyrene latex were much larger than those used in the conventional method. Reduction of the polynitrostyrene latex involved adding latex dropwise to a large excess of 6% sodium hydrosulphite-2 N potassium hydroxide solution with sodium lauryl benzene sulphonate as an emulsifier. When the mixture was heated at 70 degrees C for 4 h, the emulsion of polyaminostyrene was diazotized. The polystyrene diazonium salt latex obtained was capable of combining with 20-40% by weight of antibody protein. The immunopolystyrene diazonium latex reagents showed a positive agglutination reaction of 78-91% when mixed with serum from patients with leptospirosis and two other infectious diseases. The test, which can be completed within 3 min has been used to assay over 1200 patient samples. PMID- 2600425 TI - Comparison of immunoglobulin binding capacities and ligand leakage using eight different protein A affinity chromatography matrices. AB - The capacities of eight protein A affinity chromatography matrices were determined in a column using a purified monoclonal mouse IgG3 antibody. The capacities ranged from 0.5 to 20 mg IgG3/ml gel. Protein A-Sepharose Fast Flow exhibited the highest capacity. Each column was tested for leakage of protein A in the presence or absence of IgG3 at pH 8.9, 4.0 and 3.0. In the absence of immunoglobulins significant leakage could only be detected at pH 8.9. In the presence of immunoglobulins, considerable leakage was also found at pH 4.0, the point at which the immunoglobulins eluted. Depending on the matrix used, the IgG3 eluted from the protein A columns exhibited a contamination of 1.8-88 ppm (weight/weight) protein A. Amongst the gels with IgG3 capacities greater than 10 mg/ml, the least contamination with protein A was observed in the IgG3 fractions from immobilized rProtein A and Protein A-Sepharose CL-4B (Fermentech). PMID- 2600426 TI - An ELISA method for the quantification of anti-streptolysin-O antibodies. AB - This paper describes a new assay, based on the ELISA technique, for the quantification of antibodies to streptolysin-O (ASLO). We have compared its performances with that of a standard method (inhibition of hemolysis). Using a panel of 137 sera covering the whole range of ASLO titers, the results showed a good correlation between both methods but the ELISA method was more reproducible than the standard technique, thus represents a convenient alternative for the quantification of ASLO. PMID- 2600427 TI - Heat inactivation of serum potentiates anti-cardiolipin antibody binding in ELISA. AB - Heat treatment of sera at 56 degrees C for 30 min results in positive ELISA reactions for anti-cardiolipin antibody (aCL) in sera that had undetectable or low levels of aCL before heat inactivation. The positive, potentiated reactivity of the heated sera in the aCL ELISA could be inhibited with the cardiolipin antigen and was abolished by prior IgG depletion using staphylococcal protein A. The heat-potentiating effect of aCL binding in ELISA was evident in both normal human sera and clinical sera including sera from patients with systemic lupus erythematosus and syphilis. PMID- 2600428 TI - Enhancement of the antigen-binding capacity of incomplete IgG antibodies to Brucella melitensis through Fc region interactions with staphylococcal protein A. AB - Incomplete IgG anti-Brucella antibodies in human sera were detected using both a conventional ELISA and a modified method. In the ELISA procedure serum IgG was allowed to bind solid-phase B. melitensis antigen and, after washing, biotinylated staphylococcal protein A (BioSPA) was used as an Fc-specific tracer followed by streptavidin-HRP conjugate. In the modified method, serum IgG was co incubated with a defined quantity of BioSPA in the presence of solid-phase antigen. BioSPA bound Fc regions of serum IgG irrespective of antigen specificity whilst antibodies which were specific for Brucella bound the solid-phase antigen through their Fab regions and were detected subsequently by streptavidin-HRP. IgG anti-Brucella antibodies were detectable with a 5-25-fold increase in sensitivity when they were thus 'activated' in situ with BioSPA. In contrast with the IgG antibodies of untreated human sera, BioSPA-activated IgG showed strong antigen binding capacity and resisted the dissociation effect of the chaotropic agent, guanidine hydrochloride. In similar experiments, BioSPA did not enhance the affinity of IgG anti-Salmonella antibodies of human sera towards S. typhi antigen. The activating effect of BioSPA on the incomplete IgG anti-Brucella antibodies from patients with brucellosis possibly involves a re-orientation of Fab sites. PMID- 2600429 TI - Development and characterization of monoclonal antibodies with specificity for metallic radioisotope chelators linked to antibodies and other proteins. AB - Monoclonal antibodies with specificity for the diethylenetriaminepentaacetic acid (DTPA) portion of the GYK-DTPA (glycyl-tyrosyl-lysine-DTPA) linker structure used to chelate metals to immunoglobulins have been prepared. A significant proportion of these antibodies were lambda light chain isotype. Competition assays demonstrated that DTPA, rather than GYK, was the binding site of the antibodies tested. These monoclonal antibodies should be useful reagents for use in assays specific for the presence of the common linker structure used to chelate metallic radioisotopes to monoclonal antibodies. The antibodies tested did not discriminate between chelated and unchelated DTPA. PMID- 2600430 TI - The present status of cholera vaccine. PMID- 2600431 TI - Study of foetomaternal haemorrhage in relation to mode of delivery. AB - A study on 100 pregnant women regarding foetomaternal haemorrhage (FMH) in relation to mode of delivery with Kleihauer acid-elution technique revealed that FMH was affected by mode of delivery. Incidence of FMH was nil in normal spontaneous delivery without syntocinon drip but the incidence of FMH in normal delivery preceded by syntocinon drip was 19.05%, in forceps delivery 40%, in lower uterine caesarean section 50% and in normal delivery followed by manual removal of placenta 100%. The incidence of FMH was more in postpartum period (16%) than that in antenatal period (8%). PMID- 2600432 TI - Mortality patterns in low birth weight babies in ICDS urban slum area. AB - There were 920 live-births over the period of one year in urban slums (covering 40 anganwadi centres) of Gorakhpur city. Incidence of low birth weight (LBW) babies weighing 2.5 kg or less and those weighing 2 kg or less were 40.7% (19.8% preterm LBW and 80.2% term LBW) and 24% (25.3% preterm LBW and 74.7% term LBW) respectively. Incidence of preterm babies was 8.5%. Infections and respiratory distress were found to be the major killers of LBW babies. The neonatal mortality rate was observed to be significantly high in LBW and preterm babies. Again, babies weighing 2 kg or less and preterm were at greater risk and should be referred to specialised neonatal centres while those weighing 2.001-2.5 kg could be looked after at home by trained personnel in domiciliary newborn care. PMID- 2600433 TI - Safety of copper T as contraceptive after caesarean section. AB - Copper T was inserted in 45 cases following caesarean section. Motivation was easier, acceptance was higher and follow-up was good in this group of patients. With proper selection and careful follow-up complications could be reduced to the minimum. PMID- 2600434 TI - Role of lithium carbonate in pancytopenia following cytotoxic therapy. AB - Twenty-four patients presenting with pancytopenia following cytotoxic therapy were studied. Seventeen of them were given 900 mg/day of lithium carbonate apart from other supportive measures. Seven patients were used as controls and were not given any lithium. After 2 weeks, granulocyte count was significantly higher (p less than .05) in lithium-treated group. Platelet count was also higher though not statistically significant. PMID- 2600435 TI - Meckel's diverticulum in adults. AB - This is a study of Meckel's diverticulum in adults who had undergone surgery in the hospital. The complications of Meckel's diverticulum are compared with that of the ones mentioned in the literature. A comparative study of the clinical features and the operative findings in case of Meckel's diverticulum with ectopic tissue is also discussed. The controversy of Meckel's diverticulectomy has also been dealt with at large. PMID- 2600436 TI - Dapsone induced psychosis. PMID- 2600437 TI - Unilateral recurrent pneumothorax complicating rheumatoid lung. PMID- 2600438 TI - Priorities in primary health care in children in the seventh Five-year Plan. PMID- 2600439 TI - Income-tax tips for doctors (new starters and old ones). PMID- 2600440 TI - Drugs and diarrhoea. PMID- 2600441 TI - Fatal echovirus 7 infection during an outbreak in a special care baby unit. AB - A case of fatal echovirus 7 infection in a neonate which was probably acquired from the symptomatic mother and an outbreak of infection in a neonatal unit are described. The baby who died had extensive haemorrhagic necrosis of the brain, liver, adrenal glands and kidneys as well as disseminated intravascular coagulation. Three other babies and one member of staff were found to be infected. No other babies died. Human normal immunoglobulin was administered to all babies on the unit. PMID- 2600442 TI - Recurrent Listeria monocytogenes meningitis in a heart transplant recipient. AB - A case of recurrent Listeria monocytogenes meningitis is reported, the two episodes arising 4 months and 8 months after the patient had received a heart transplant. Both episodes immediately followed increased doses of corticosteroids for allograft rejection. The source of infection was not identified. Previous reports and possible explanations of recurrent L. monocytogenes infection are reviewed. PMID- 2600443 TI - Osseous sporotrichosis. AB - We report on four patients with osteomyelitis due to Sporothrix schenckii who were successfully treated with potassium iodide. PMID- 2600444 TI - Pleuropulmonary infection due to Clostridium subterminale. AB - Clostridial pleuropulmonary infection in a patient with suspected pulmonary embolism is described. Clostridium subterminale was recovered as the sole pathogen on several occasions despite antibiotic therapy. The patient died of cardiac failure after a complicated course in hospital. Clostridium subterminale is a rare pathogen and has not so far been reported as the sole cause of pleuropulmonary infection. PMID- 2600445 TI - Cryptosporidiosis in white patients in South Africa. AB - From January to December 1987, faecal specimens received from 3186 white children and adults with diarrhoea were examined for the presence of cryptosporidial oocysts. They were found in 129 patients, an incidence of 4.1%. Most of the infections were in children less than 5 years of age, giving an incidence of 6.2% in this age group. Cryptosporidium was usually the only pathogen detected, additional pathogens being identified in only 19 cases. A marked seasonal increase in incidence was seen in 107 cases (82.9%) between January and May, that is in late summer and early autumn in South Africa. PMID- 2600446 TI - Brucella thyroiditis. PMID- 2600447 TI - HIV-related thrombocytopenia: is zidovudine a therapeutic option? PMID- 2600448 TI - Topical zoonosis. PMID- 2600449 TI - Cryptosporidiosis as a cause of chronic diarrhoea in a patient with insulin dependent diabetes mellitus. PMID- 2600450 TI - Which atypical pneumonia? PMID- 2600451 TI - Splenic vein thrombosis in patients with acute pancreatitis. AB - We performed a retrospective autopsy case-control study to identify clinical characteristics of acute pancreatitis associated with splenic vein thrombosis. Age, sex, spleen weight, presence or absence of gastrointestinal hemorrhage, and pancreatic pseudocyst were not associated with splenic vein thrombosis. Patients with peak serum amylase over 10,000 U/L were at high risk for splenic vein thrombosis. We conclude that, of the factors examined, only the peak serum amylase may be of value in diagnosing splenic vein thrombosis in patients with acute pancreatitis. PMID- 2600452 TI - Dose-dependent inhibition by cyclosporine A of the induction of pancreatic ornithine decarboxylase (ODC) in rats. AB - The effect of cyclosporine A (CsA) and alpha-difluoromethylornithine (DFMO) on the camostate-induced increase in pancreatic ornithine decarboxylase (ODC) activity and polyamine biosynthesis has been studied in vivo. Six hours after application of the synthetic trypsin inhibitor camostate (200 mg/kg b wt orally) pancreatic ODC activity increased about 140-fold and putrescine concentration about ninefold. CsA inhibited the elevation of both parameters in a dose dependent manner. CsA pretreatment for 3 d with doses of 7.5, 10.0, and 12.5 mg/kg b wt orally once a day and consecutive CsA blood levels 24 h after the last CsA application of 751 +/- 62, 968 +/- 70, and 1,395 +/- 79 ng/mL, respectively, resulted in a complete inhibition of the camostate-stimulated increase in pancreatic ODC activity and putrescine concentration in vivo. DFMO (2% in drinking water and additionally 300 mg/kg b wt intraperitoneally at 8 AM, 12 noon, and 4 PM) inhibited the increase in both, ODC activity, and putrescine, significantly in an equipotent degree as 2.5 mg CsA/kg b wt, whereas higher doses of CsA proved to be more effective than DFMO in the chosen subtoxic dose. In all cases, no significant changes in pancreatic spermidine and spermine concentration, DNA and protein content, or pancreatic and body weight were observed. It is concluded that CsA in doses used for immunosuppression in clinical practice is a very potent and more effective inhibitor of ODC activity and polyamine synthesis in vivo than DFMO. This ODC inhibitory effect of CsA is a further detail to elucidate the up to now incompletely understood mechanisms of action of this immunosuppressive agent. PMID- 2600453 TI - The effect of gastrointestinal hormones on the incorporation of tritiated thymidine in the pancreatic adenocarcinoma cell line (WD PaCa). AB - In view of the trophic action of gastrointestinal hormones on the exocrine pancreas, the effects of secretin, octapeptide of cholecystokinin (CCK-8), and desglugastrin on the growth of hamster pancreatic well differentiated adenocarcinoma were investigated in vitro. Desglugastrin exhibited the greatest effect on thymidine incorporation into these cells after a lag period of 96 h. Doses of desglugastrin in the range from 30 to 270 ng/mL caused a significant and dose-dependent increase in thymidine incorporation. Higher doses of this peptide led to a decreased response. Secretin also increased thymidine incorporation, but the response was less than that induced by gastrin. Prolonged incubation with secretin for 96 h increased tritiated thymidine incorporation in a log-dose fashion in the range of 30 to 270 ng/mL. Doses of CCK-8 in the range of 90 to 810 ng/mL significantly increased thymidine incorporation after 48 h of incubation. Following 72 h of incubation, only the dose of 270 ng/mL continued to exhibit a significant stimulation. Our study suggests that the gastrointestinal hormones could directly increase the growth of pancreatic carcinoma cells, act synergistically with endogenous growth factors, or stimulate the local production of these factors. In any event, our results that gastrin, secretin, and CCK can stimulate the growth of pancreatic ductal tumor cells in tissue cultures, support earlier findings on normal and malignant pancreatic parenchyma. PMID- 2600454 TI - Mesenteric venous infarction in acute pancreatitis. AB - Segmental intestinal necrosis is a rare complication of acute pancreatitis. The pathogenesis of intestinal necrosis in acute pancreatitis has previously been attributed to arterial thrombosis, but we have observed an unusual case of segmental small intestinal infarction associated with pancreatitis that could not be explained by this mechanism. In our patient, the clinical, gross, and microscopic features were compatible with mesenteric venous infarction. A search of the literature revealed three previous cases of small intestinal infarction in patients with acute pancreatitis with similar clinical and histologic findings. Mesenteric venous infarction of the colon has also been described in association with acute pancreatitis. It seems clear that mesenteric venous infarction represents an additional cause of intestinal necrosis in patients with acute pancreatitis, and may result from changes in clotting mechanisms known to be induced by acute pancreatitis. PMID- 2600455 TI - [A study on the examination of the incidences of streptococcal infectious diseases in the nationwide and the regional surveillance information of infectious diseases in Japan (1st report)]. AB - As the first step to examine the incidences of streptococcal infectious diseases for the nationwide and the regional surveillance information of infectious diseases in Japan, the number of patients with streptococcal infectious diseases per year or week and the hospitals in the surveillance systems in 47 prefectures from 1982 to 1987 were compared. It was found to have the tendency that the numbers of the patients were comparatively more in Hokkaido, Tohoku, partial areas of Kyushu and Shikoku than in other regions, and more in rural areas than in urban areas. Because of the deviation from the tendency, however, it was also suggested that the information of the disease in some prefectures might be poor. Although ratios of no. of the patients against no. of patients with exanthema subitum in 16 prefectures, respectively, were calculated and compared, it was be not enough to analyze the difference among the incidences of streptococcal infectious diseases in these prefectures. PMID- 2600456 TI - [Relationship of serum streptococcal antibodies to carrier state of beta hemolytic streptococcus in throats of healthy schoolchildren]. AB - The relationship of ASO, ASK and ASP to carrier state of beta-hemolytic streptococcus in throats of healthy schoolchildren was examined from September, 1980 to May, 1987. The responses to ASO significantly increased in children who detected group A, C and G streptococcus, and ASK in group A and G, and ASP in group A. The responses were especially high in children who detected group A, C and G streptococcus one after the other through the term of research, and in children detected another T type of streptococcus one after the other. Relatively high titers of ASO and ASK were obtained in sera of children from whom some groups or T types of streptococci were isolated several detection times. ASP titers were not concerned with these times. The elevation of antibodies in paired samples were found as follows; 7 cases in ASO, ASK and ASP together, 42 cases in ASO and ASK together, 3 cases in ASK and ASP together, 2 cases in ASO and ASP together, 41 cases ASO only, 38 cases in ASK only, 7 cases in ASP only. Among these cases with elevation of antibodies titers, several kinds of the change of streptococcal carrier state were observed between obtaining serum of twice. Especially 15 cases with change of carrier state from group A to group A were noticed. Among these 15 cases, 11 cases isolated another T type strain through the term of research, or found to contain the research-time when no streptococcal strain was detected. Both long term carrier state of the same group or the same type of streptococcal strain and change of carrier state of streptococcal group or T type lead the elevation of ASO and ASK titers. PMID- 2600457 TI - [Ecological studies on hemolytic streptococci in aged population]. AB - The pattern of group distribution of hemolytic streptococci and the source of specimen, when these organisms were isolated from the clinical specimen of the aged, were quite different from that of streptococcosis among children. The isolation frequency from the upper respiratory tract was rather low in comparison to the other specimen, such as sputum, exudate and urine. Both groups B and G were predominant among isolates from sputum, B more prevailing than G from exudate, and the isolates from the urinary tract were consisted almost solely of group B. These trends have been unchanged in the past 3 years. Normal pharyngeal streptococcus flora among the aged also differ from that of healthy children, the carrier rate being rather low, and groups B and G, instead of A in the case of children, being predominant. This pattern of group distribution, among the isolates of normal pharyngeal streptococci of the aged, seemed to be reflected on that of isolates from clinical specimen, especially those from the sputum. The type distribution of group B isolates from normal throat swabs of the aged resemble that of clinical isolates from the same generation, types Ia and III dominating in both cases. PMID- 2600458 TI - [The trends of hemolytic streptococci isolated from clinical specimens in hospitals in Saitama during the period of 1979-1987]. AB - In order to analyze the trends of hemolytic streptococcal infections, we have investigated the source of clinical specimens, monthly isolation rates, and the isolation rates by sex and age o patients of 6,440 hemolytic streptococci (group A, B, C and G) isolated from clinical specimens in hospitals in Saitama during the period of 1979-1987. 1) Serological group of 6,440 hemolytic streptococci isolated from clinical specimens were 4,691 (72.9%) isolates of group A, 1,535 (23.8%) isolates of group B, 47 (0.7%) isolates of group C, and 169 (2.6%) isolates of group G. 2) The main clinical sources of hemolytic streptococci, group A streptococci were 4,243 (90.7%) isolates from throat swabs, 117 (2.5%) isolates from ear secretions, 87 (1.9%) isolates from nose secretions, and 58 (1.2%) isolates etc., group B streptococci were 647 (42.2%) isolates from urines, 446 (29.1%) isolates from vaginal swabs, 127 (8.3%) isolates from throat swabs, 118 (7.7%) isolates from semen, 55 (3.6%) isolates from urethral secretions, 13 (0.8%) isolates from blood, and 9 (0.6%) isolates from cerebrospinal fluid etc.. 3) The monthly isolation rates of hemolytic streptococci, showed that group A streptococci had a general trend by the season, that is, the highest ratio in winter and the lowest ratio in summer, group B streptococci was not influenced by the season. 4) The isolation rates by sex of patients showed that group A streptococci had no difference between male and female, however, group B streptococci showed that the isolation rate of female was higher than that of male with the ratio of 7 to 3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600459 TI - Cardiac transplantation and mechanical circulatory assistance: the Texas Heart Institute experience. AB - From January 1984 to September 1988, 245 heart transplants were performed at our institution. During this period, 53 staged cardiac transplant procedures were performed using an intraaortic balloon pump (IABP), an extracorporeal centrifugal blood pump (ECBP), an intracorporal left ventricular assist device, and a total artificial heart. Thirty-four (64%) patients underwent subsequent cardiac transplantation and 28 (53%) were discharged. Our data indicate that patients who suffer rapid onset of heart failure and undergo early circulatory support are suitable candidates for successful staged cardiac transplantation. We have also used mechanical support to treat severe heart failure after transplantation, using IABP and ECBP support, as well as an intraarterial axial flow pump. In immunosuppressed patients, infection is the critical issue affecting outcome. There is a need for development of smaller, simpler, less invasive devices with the capacity to provide both systemic and pulmonary circulatory support. PMID- 2600460 TI - [Experimental study on myocardial preservation with perfluorochemical]. AB - The effect of perfluorochemical as cardioplegic solution was studied with isolated canine hearts. They were divided into two groups as follows each consisting of ten, and cardioplegia was made every 30 minutes during 3 hours of ischemia. Group I: The solution was oxygenated to PaO2 of 542 +/- 67 mmHg (mean +/- SD). Group II: The solution was deoxygenated to PaO2 of 55 +/- 12 mmHg. Both temperature were 20 degrees C. After 3 hours cardiac arrest, the hearts were fixed to the perfusion unit filled up with the diluted blood. Then hemodynamic and biochemical variables were measured every 30 minutes. There were some significant differences between the groups. Hemodynamic indices especially negative LV max dp/dt were recovered excellently in Group I but not so much in Group II. Negative LV max dp/dt, which was the distinction of the diastole, showed significant difference more than positive LV max dp/dt, which was the distinction of the systole. It was considered that under the same condition, negative LV max dp/dt reflected not only compliance but also preparatory ability of the left ventricle, and it could be one of the important indices evaluating cardiac function. As regarding metabolism, delivery of oxygen with cardioplegic solution was good for the aerobic metabolism also after reperfusion, and in these circumstances, catecholamine was available effectively to the hearts. The conclusion is as follows. It is important for myocardial preservation to suppress the anaerobic metabolism and to keep the circumstances in which catecholamine was available effectively. And oxygenated PFC is good to preserve myocardium and useful as cardioplegic solution. PMID- 2600461 TI - [Pulmonary complication after resection of lung cancer--difficulty in expectoration and cough dynamics]. AB - From January 1975 to December 1986, 415 patients were operated for primary lung cancer. Postoperative pulmonary complications were observed in 83 patients and among them 48 patients (57.8%) suffered from difficulty in expectoration. Postoperative expectoration mostly depends on the ability of coughing. To evaluate cough dynamics, expiratory flow-rate and volume at voluntary maximal cough were measured. The more expiratory flow rate and volume a cough has, the more effective it is for expectoration. In those patients with decreased FEV1.0, or respiratory muscle weakness because of emaciation and aging, or severe pain in the wound, the cough dynamics was decreased. By cleaning retained secretions in the respiratory tract, postoperative pulmonary complications would be prevented. However in cases where the decrease in postoperative cough dynamics is predictable, application of limited resection should be considered as well. PMID- 2600462 TI - [A study on clinical findings and surgical treatment of pulmonary mycosis]. AB - Between 1974 and 1987, 14 patients (10 male and 4 female) underwent thoracotomy for treatment of pulmonary mycosis. They were studied on their clinical findings and surgical treatment. The median age was 48 years (range 19 to 71 years). Fourteen cases consisted of 9 aspergillosis and 5 cryptococcosis. None of them was either debilitated or immunosuppressed before falling ill. Five of the 14 patients had other pulmonary disease and 11 had symptoms; i.e. hemoptysis or bloody sputum in 4 cases, chest pain in 3, fever in 3, cough and sputum in 2. Nine aspergillosis consisted of 4 aspergilloma, 3 aspergillus pneumonia and 2 aspergillus empyema. Three cases of aspergillosis occurred in preexisting cavity. Five cryptococcosis consisted of 3 pseudotumorous, 1 disseminated small nodular, and 1 infiltrative types. Preoperative diagnosis was as follows; pulmonary mycosis 5, pulmonary tuberculosis 4, lung cancer 3, empyema 1 and hydropneumothorax 1. Four patients underwent partial resection, 8 lobectomy, 1 pneumonectomy, 1 muscle prombage and thoracoplasty. The prognosis is satisfactory. All patients are alive and has no recurrence. On histopathological examination, in aspergilloma cases, invasion of aspergillus to surrounding lung tissue was not seen. In addition to well-known fact that blood-borne dissemination hardly occurred in aspergilloma in contrast to cryptococcosis. These findings suggest that aspergilloma and solitary lesion of cryptococcosis should be resected, and adjuvant chemotherapy should be accompanied for cryptococcosis. PMID- 2600463 TI - [Experimental study of coronary reactive hyperemia--effects of hypothermia and potassium cardioplegia]. AB - A hyperemic response on dog hearts following myocardial ischemia for 10 minutes has been studied in reference to myocardial protection with cardioplegia and hypothermia. Experimental animals were divided into four groups according to the difference in temperature and with or without cardioplegia during ischemia of the hearts. Group I (n = 7) succumbed to a normothermic ischemia. Group II (n = 6) had normothermic ischemia following infusion of 8 ml/kg of a normothermic cardioplegic solution. Group III (n = 7) had ischemia under moderate hypothermia (28 degrees C). Group IV [n = 7) had hypothermic ischemia following infusion of 8 ml/kg of hypothermic cardioplegic solution. A percent repayment of the flow debts in groups I, II, III, and IV were 234.6 +/- 38.3%, 101.5 +/- 40.8%, 134.5 +/- 50.0% and 112.8 +/- 36.5%, respectively. There was significant difference between group I and group II and IV (p less than 0.001) and group III (p less than 0.02). Peak flow in reactive hyperemia compared with control flow were 605.4 +/- 131.1%, 328.3 +/- 60.2%, 288.8 +/- 79.7% and 282.2 +/- 65.4% in each group I, II, III, and IV, respectively. The value in group I was significantly high in comparison with others (p less than 0.005). Depression of oxygen consumption was observed in groups with hypothermia as well as with cardioplegia. A hyperemic response was low in cardioplegia and/or hypothermia group. These data are suggestive of a beneficial use of cardioplegia and hypothermia on cardiac surgery through the observation of coronary reactive hyperemia after myocardial ischemia. PMID- 2600464 TI - [Effect of the intra-aortic balloon pumping on renal function]. AB - The effect of IABP on renal function were studied in 41 patients who underwent cardiac operation. Eight of the 41 patients were acute myocardial infarction (AMI), 4 were unstable angina, and 29 were postoperative low cardiac output syndrome (LOS). In 12 patients with AMI and unstable angina, an IABP was inserted preoperatively. Urinary N-acetyl-beta-D-glucosaminidase (U-NAG) and fractional excretion of beta 2-microglobulin (FE beta 2M) in addition to conventional renal parameters such as creatinine clearance (Ccr) and free water clearance (CH2O) were measured before and during IABP. Patients were divided into three groups according to its responses within 6 to 12 hours of IABP. In Group I (25 cases) which showed the significant improvement of renal and cardiac function, the values of Ccr, CH2O improved to normal range within 6 hours after initiation of IABP. In Group II (4 cases) which showed improved renal functions in spite of insufficient improvement of cardiac functions, renal functions improved 12 hours late, showing 6 hours delay from Group I. In Group III (8 cases) both the renal functions as well as cardiac functions did show no improvement. Retrospective study demonstrated that the patients whose Ccr improved above 50 ml/min/1.48 m2 and CH2O reduced below -0.55 ml/min/1.48 m2 and within 12 hours after initiation of IABP were able to wean from IABP. However, the patients whose Ccr reduced less than 50 ml/min/1.48 m2 and CH2O grown worse above -0.55 ml/min/1.48 m2 for longer than 12 hours could not wean from IABP. And the patients whose U-NAG and FE beta 2M reduced less than 20 U/l and 3.0% during IABP support were able to wean from IABP. In conclusion, IABP was effective therapy for the patients with cardiogenic shock, LOS, and renal dysfunction. PMID- 2600465 TI - [Extended aortic arch anastomosis for aortic coarctation in neonate and early infancy--experience in 5 patients]. AB - The aortic coarctation (CoA) was repaired with extended aortic arch (AA) anastomosis in 5 consecutive patients, 2 in neonate and 3 in infancy, ranging in age from 3 to 106 days. The associated lesions were ventricular septal defect in 2, atrial septal defect in 2 and complete atrioventricular canal in 1. Patent ductus was found in 4 and prostaglandin E1 was required in 2 with response in 1 patient. The AA was hypoplastic in 2 patients with arch to descending aorta diameter ratio below 0.5. The CoA repair was performed as the first procedure in all. The primary anastomosis was possible in all between AA and the descending aorta without undue tension after removal of the all ductus tissue and extensive mobilization of the aorta. Aortic clamp time was 28 minutes in average. The intraoperative pressure gradient after repair across AA was 0 to 10 mmHg (average 4.6 mmHg). All except 1 with preceding hepatic dysfunction tolerated the procedure without complication or operative death. Postoperative evaluation at 1 to 11 months showed no significant pressure gradient between upper and lower extremities. This method appears to be useful for CoA in early infancy particularly when AA is hypoplastic. PMID- 2600466 TI - [Prevention of spinal cord ischemia after cross-clamping of the thoracic aorta- monitoring of spinal cord perfusion pressure and somatosensory evoked potentials]. AB - The pressure difference between the mean distal aortic pressure (MDAP) and the cerebrospinal fluid pressure (CSFP), defined as the spinal cord perfusion pressure (SCPP), as well as somatosensory evoked potentials (SEP) were monitored intraoperatively to detect and prevent intraoperative spinal cord ischemia in 24 patients who required cross-clamping of the descending thoracic aorta. A temporary axillo-femoral shunt, utilizing a 10 mm woven Dacron tube graft, was employed in 10 patients and partial cardiopulmonary bypass was employed in fourteen. Ischemic SEP changes were seen in six patients. Two patients, whose SCPPs were 32 and 35 mmHg, showed a complete loss of SEP and subsequently developed paraplegia. In the other four cases, increase of the MDAP and/or withdrawal of cerebrospinal fluid were performed to increase the SCPP to more than 60 mmHg when ischemic SEP changes occurred. The SEP gradually recovered in two of these cases. The ischemic SEP changes seen in one patient, who had the longest aortic cross-clamping time, (175 minutes) returned to normal immediately after unclamping. In another case, who had a thoracoabdominal aortic aneurysm, the intercostal arteries were reimplanted since the ischemic SEP changes did not revert. These four patients recovered without any neurological deficit. In the other 18 cases without ischemic SEP change, SCPP was kept at more than 40 mmHg during aortic cross-clamping. We conclude that the SCPP should be maintained at more than 40 mmHg during aortic occlusion, and increased to more than 60 mmHg when ischemic SEP changes occur, by increasing MDAP and/or withdrawing cerebrospinal fluid in order to prevent postoperative paraplegia. PMID- 2600467 TI - [Operative indication for aortic valvuloplasty by rasping procedure from the point of histopathologic evaluation]. AB - Rasping procedure is proposed by the author as one of the methods of aortic valvuloplasty and defined as shaving the surface of rheumato-degenerative aortic valve by using the electric rasp. Materials were the removed rheumato degenerative aortic valves as specimen, and classified into 3 groups. The first group (type I) was valve lesion limited to valve free edge, second (type II) was mild thickening entirely, third (type III) was severe thickening with calcified degeneration. Rasping procedure was performed for the thickened portion of the valve specimen by the electric rasp. Morphologic examinations after rasping procedure were evaluated by histopathologic study. Histopathologically, there was hyaline degenerative connective tissue in superficial layer above the collagen fiber's layer in rheumato-degenerative thickened valve in type I. This hyaline degenerative connective tissue was considered to be fragile and pathologic in the tissue structure. Rasping procedure could remove this connective tissue layer. Type II, there was the similar finding to the type I from the free edge to the mid portion of the cusp. So, Rasping procedure was effective for type I and type II valve degeneration. On the contrary, the calcified lesion (type III), rasping procedure was not effective in valve coaptation and the pathological findings showed the fragmentation in the calcified layer. In the pathological comparison with the slicing procedure for type II by the surgical knife, there was a crack and cleft in the collagen fiber's layer in the case of slicing procedure. It can be concluded the results of histopathological study of the rasping procedure proved to be superior to the conventional aortic valvuloplasty (slicing method). PMID- 2600468 TI - [Experimental study of materials used for intra-atrial baffle for the Mustard operation]. AB - An experimental model was developed to study the fate of prosthetic materials used for the construction of an intra-atrial baffle for the Mustard operation. Total atrial septa were replaced in sixteen puppies with autologous pericardium (n = 3), glutaraldehyde-preserved canine pericardium (n = 4), glutaraldehyde preserved porcine pericardium (n = 3), EPTFE reinforced sheet (Gore-Tex sheet, n = 3) and EPTFE reinforced cardiovascular patch (Gore-Tex patch, n = 3). Septal replacement was performed under total circulatory arrest and surface induced deep hypothermia. All animals were sacrificed six months after the septal replacement. Pathological examination revealed that all septal grafts were well healed, completely covered by neoendothelium and had contracted to approximately 60% of their original size. There were no significant difference between groups. Histologic examination showed the good tissue adaptation of autologous pericardium and Gore-Tex patch materials. The thinnest layers of neoendothelium covered autologous pericardial baffle. Glutaraldehyde-preserved pericardium and Gore-Tex sheet did not adapt well to host atrial tissue. These materials were easily detached from their neoendothelial substrates. It was concluded that the autologous pericardium as well as a Gore-Tex patch may be superior to other prosthetic materials used for the construction of an intra-atrial baffle for the correction of transposition of the great arteries. PMID- 2600469 TI - [Myocardial protection of temperature]. AB - The effects of myocardial temperature on 120-minute preserved hearts were studied on heterotopically transplanted hearts of rats of isogeneic strain. Rats were divided in the following groups; the control group, the 0 degree C preservation group, the 5 degrees C group, the 10 degrees C group, the 15 degrees C group and the 20 degrees C group. Experiments were divided into the acute stage experiments and chronic stage experiments. The former included electron microscopic studies of the myocardium of heart transplants and serum enzymes of recipients. In the chronic stage experiments, the percentage of fibrosis was compared as an index of success. No hearts of the 20 degrees C group resuscitated, and by the indices of acute stage experiments, the 10 degrees C group and the 15 degrees C group showed considerable impairment; other groups showed less damage of the same degree. The chronic stage experiments indicated that the 0 degree C group was best, followed by the 5 degrees C group in the increasing order of temperature, evaluated by the rate of fibrosis. It may be concluded that hypothermia close to the freezing point has the best protective effects on the myocardium. Cold injury, even if present, may be transient and not harmful when ischemia is about 120 minutes. Comprehensive evaluation of various factors contributing isograft survival should include not only various methods examined in the acute stage but also an over-all evaluation of fibrosis in the chronic stage, since the myocardium of the graft shows a variability of findings in the acute stage. PMID- 2600470 TI - [The effects of transfusion of irradiated blood upon cellular immune response in patients underwent open heart surgery]. AB - The purpose of this paper is to demonstrate the effect of the transfusion of blood received 1500 rad exposure upon the immune response in 14 patients underwent various type of cardiac surgery. 13 patients received known amounts banked blood and irradiated fresh blood, while one patient received a lot of amounts of banked and irradiated and non-irradiated fresh blood. The authors studied the numbers of lymphocytes as well as lymphocyte subsets such as pan-T cells, B cells, helper/inducer T cells (TH/I), cytotoxic/suppressor T cells (Tc/s), active T cells, natural killer (NK) cells and NK cell activity during two weeks after surgeries. In all 14 patients, pan-T lymphocytes decreased markedly in a few days after surgeries, but increased to higher levels on the eight postoperative day than the levels preoperatively. TH/I and TC/S lymphocytes changed on the similar pattern as pan-T lymphocytes. Active T and B cells did not change significantly in two weeks. The number and activity of NK cells gave the lowest levels on the second postoperative day and did not recover to the preoperative levels in two weeks. One patient received non-irradiated fresh blood showed the similar immune response as other 13 patients, while he gave the lower levels than others did. This patient died of graft-versus-host disease (GVHD) like syndrome on the 36th postoperative day. It may be thought that the transfusion of irradiated blood would prevent the host from GVHD and gave the better effects on the immune response than that of non-irradiated blood following open-heart surgeries. PMID- 2600471 TI - [Clinical experience of bovine internal mammary artery graft (BIOFLOW) for coronary artery bypass surgery]. AB - Bovine internal mammary artery graft (BIOFLOW: BIOVASCULAR INC. Netherlands) has been used for coronary artery bypass grafting (CABG) in 8 patients since May 1988 at Osaka Medical College Hospital. There were 4 males and 4 females. Mean age was 66.9 year-old ranged from 62 to 72. Two were emergency CABG and other six had inadequate saphenous veins. The internal mammary artery and/or the saphenous vein were concomitantly used in all patients. Number of grafts was 2 to 6 with the mean of 2.9 and BIOFLOW (phi 3 mm) was anastomosed to 2 left anterior descending arteries and 6 right coronary arteries, the mean graft flow of BIOFLOW was 72.5 ml/min ranged from 52 to 120 ml/min. One patient died of ventricular arrhythmia on 5 postoperative day. There was no new Q wave infarction. Postoperative angiogram within 2 months showed 4 of 5 BIOFLOW grafts were patent, and no stenosis was found in those patent grafts. All survivors returned to home with a freedom from angina. From our experience, although the number was small and the follow-up period was short, BIOFLOW can be expected as an conduit of choice for CABG when the saphenous vein was not available and the internal mammary artery and the gastroepiploic artery were not enough to accomplish the complete revascularization. PMID- 2600472 TI - [Surgical treatment of right subclavian aneurysm--a case report]. AB - A case of arteriosclerotic aneurysm of right subclavian artery is reported. The patient was 74 years old male. A huge arteriosclerotic aneurysm was found at the origin of right subclavian artery. Calcification of thoracic aorta and arch vessels was prominent. Under the temporary bypass between brachiocephalic artery and right common carotid artery, replacement of the aneurysm with 8 mm Dacron graft was successfully performed. To avoid the systemic embolism, partial clamp was applied to intact arteries. As the perfusion of the brain was maintained through the temporary bypass during the reconstruction of right common carotid and subclavian arteries, intracranial complication was prevented. PMID- 2600473 TI - [Three cases of successful early operations of post-infarction ventricular septal perforation]. AB - We reviewed three cases who underwent early operations for post-infarction ventricular septal perforation. Three patients were 56-year-old male, 66-year-old female, and 62-year-old female. These three cases had sustained antero-septal infarction with perforation. The periods to operations were 11 days, 86 hours, and 76 hours from the onsets of myocardial infarction. And 70 hours, 51 hours, and 42 hours from the onset of postinfarction ventricular septal perforation. Operations were performed after cardiac standstill using cold potassium cardioplegia and topical cooling. At first ventricular infarctectomy was performed and a large Teflon patch was used to create the septum after resection of the necrotic septum, and then resulting defect in the right and left ventricles was closed with Teflon strips and interrupted mattress sutures, incorporating the patch in the repair. Postoperative clinical courses were not smooth, but all the cases were going well. So we believed to get good results for early operations of post-infarction ventricular septal perforation, unless operative chances were lost. PMID- 2600474 TI - [A simultaneous operation of A-C bypass and replacement of abdominal aortic aneurysm--a successful case]. AB - A 70-year-old man was successfully operated on A-C bypass for coronary triple vessel disease and replacement of abdominal aortic aneurysm. The two different procedures were performed simultaneously under cardio-pulmonary bypass. This simultaneous operation can provide benefits of shortening operating time and of clamping easily the abdominal aorta. PMID- 2600475 TI - [Surgical treatment of a case of arrhythmogenic right ventricular dysplasia with local myocardial resections]. AB - A 39-year-old man who was diagnosed as ARVD (arrhythmogenic right ventricular dysplasia) with nonischemic sustained ventricular tachycardia (VT) was successfully treated by surgical resection of two parts of the right ventricular free wall, one was the site of earliest excitation during induced VT and the other was an area where delayed potentials were detected during sinus rhythm. A surface mapping was made by means of a computer guided system. A preoperative study of endocardial mapping and a programmed electrical stimulation test were an useful adjunct for surgical management of ARVD. After surgery VT could not be induced by triple extrastimuli and up to now there has been no recurrence of VT more than 2 years after surgery without medication. PMID- 2600476 TI - [A case report of Bentall procedure for annulo-aortic ectasia associated with right coronary artery dissection]. AB - A 30-year-old man who had annuloaortic ectasia associated with aortic insufficiency owing to marked annular dilatation was treated by replacement of the ascending aorta and aortic valve with a composite graft. It was necessary to transpose the origin of the coronary artery because of the development of dissection to right coronary ostia. We have applied the Bentall procedure with aorta coronary bypass between the right coronary artery and the aortic prosthesis with the use of saphenous vein graft. His post operative course is uneventful and engaging full work 18 month after operation. This technique is useful for the case of annuloaortic ectasia associated with difficulty coronary anastomosis such as coronary artery dissection, obstruction or dislocation. PMID- 2600477 TI - [Two cases reports of neurologic complications after aortic aneurysm operation]. AB - Two cases with dissecting aortic aneurysm of DeBakey type IIIb were treated by graft replacement of the descending thoracic aorta under temporary bypass (Heparinized Hydrophilic Polymer shunt tube) with concurrent somatosensory evoked potential (SEP) monitoring. The SEP was unchanged during operation in both cases, and three sets of intercostal or lumbar arteries were reattached in case 2. In case 1 anterior spinal artery syndrome occurred below the fourth thoracic level (T-4) and right side hemiplegia immediately after the operation. Case 2 had normal neurological function initially after recovering from anesthesia but showed Brown-Sequard syndrome below the first lumbar level (L-1) two days later. In both cases, neurologic disturbance gradually recovered, 19 months postoperatively, case 1 can walk with assistance, and case 2 is able to resume his former activity. The probability of the prevention of neurologic deficits is discussed. PMID- 2600478 TI - [A case of dumb-bell-like neurilemmoma of the posterior mediastinum]. AB - A 56 year-old female was pointed out an abnormal shadow on chest X-ray film for the lung cancer screening study. Chest X-ray film showed a round mass shadow at the right superior mediastinum. Chest CT scan revealed the mass was in the paravertebral area abutting on the 2nd thoracic vertebral body and had extended into the intervertebral foramen. Preoperative diagnosis was a dumb-bell-like neurogenic tumor. Operation was carried out by posterior approach in the prone position. At first thoracotomy was done by removing the paravertebral portion of the 2nd and 3rd ribs, and then hemilaminectomy was added. Both the intrathoracic and intraforminal portions of the tumor were completely exposed, and excised. Pathological examination demonstrated the tumor was a typical neurilemmoma originating from the 2nd intercostal nerve. When a neurogenic tumor of the posterior mediastinum has an intraspinal extension, a posterior approach by a simultaneous thoracotomy and laminectomy will be useful to remove the tumor at one sitting. PMID- 2600479 TI - [A case of localized pleural mesothelioma]. AB - A 68-year-old male with localized pleural mesothelioma was described. The tumor was removed surgically in association with left upper pulmonary lobe and regional lymph nodes, since low grade malignancy had been suggested by preoperative needle biopsy. The operative and macroscopic findings revealed that the tumor was well encapsulated and arise from visceral pleura of S3 segment of left upper lobe, projecting into pleural cavity as a pedunculated mass. The tumor measured 9 X 6 X 4 cm in diameter. Based on electron microscopic and immunohistochemical findings of the tumor, the origin of tumor cells was discussed. PMID- 2600480 TI - [Simplified operative technique for thoracoabdominal dissecting aneurysm]. AB - A graft with branches is used to reconstruct the extensively dissected thoracoabdominal aorta. Anastomoses of the proximal end of the main graft distal to the left subclavian artery and the side branch to the distal aneurysmal descending thoracic aorta were first undertaken after the preparation of both ends under the iliac vein-artery partial bypass. A main graft with a Y graft extension was anastomosed distally to iliac arteries. This permits the blood flow within the aneurysm and the main graft to the extremities until splanchnic and spinal cord arteries have individually been transferred to the main graft. Ischemic time of the splanchnic and spinal cord arteries, using this technique, can be minimized within 10 minutes to each in the total replacement of descending thoracic and abdominal aorta. PMID- 2600481 TI - [Aortic disruption after operation for pectus excavatum in a infant with Marfanoid hypermobility syndrome]. AB - An elective correction of pectus excavatum was carried out in a 5-year-old boy who subsequently died on the sixth postoperative day from rupture of descending aorta. The rupture which was longitudinal disruption 5 cm in length occurred 3.2 cm distal to the orifice of the left subclavian artery. Histological examination revealed that cystic medial necrosis was present in the thoracic and abdominal aorta. This boy had a slightly tall frame, arachnodactylia, hyperextensibility of the joint, but no ocular symptoms. His skin was excessively elastic and friable. Although he had been identified with characteristics to neither Marfan syndrome nor Ehlers-Danlos syndrome, he was thought to be with Marfanoid hypermobility syndrome. Since aortic dilatation was 4.6 cm in diameter and no valvular involvement was detected preoperatively, only the cosmetic surgery for the pectus excavatum was made. The correction of pectus excavatum might be a trigger of aortic disruption. We must mention that aortic disruption may be occur besides the dilated portion in case of connective tissue disease. PMID- 2600482 TI - [Pathological findings of the aortic wall at the site of ligation against the rigid rings of an intraluminal graft for acute DeBakey type I aortic dissection]. AB - A ringed intraluminal graft has been utilized in the surgical treatment for dissecting aneurysm since 1978. Histological findings of the aortic wall long after surgery, however, have not been described in detail, and concern remains about possible pressure necrosis at the point of encirclement. The following report is for a case of acute type I aortic dissection which required the use of an intraluminal surgical graft in a patient who died eight months postoperatively of a disease unrelated to previous surgical management. The pathological findings at autopsy were as follows. At the site of circumferential ligations around the aorta, 1) discontinuity of the elastic fibers in the media was found only at the outer surface, 2) there was no compression necrosis in the outer half of the media, although a dark shade of elastic fibers was recognized, 3) there were no pathological changes in the inner half of the media. In addition, complete repair of the intimal tear as well as closure of the false lumen replaced by collagen fibers was confirmed histologically in the whole length of aorta where the intraluminal graft had been placed. We conclude that concerns about the fragility of the aortic wall at the site of circumferential ligation, the migration of prosthesis, and the formation of thrombi is alleviated by these pathological observation. PMID- 2600484 TI - [A case of successful surgical treatment of straddling tricuspid valve associated with dextrocardia and VSD]. AB - A case of straddling tricuspid valve associated with dextrocardia and VSD was presented. Closure of ventricular septal defect and tricuspid valve replacement were performed on this patient. Since the straddling septal leaflet of the tricuspid valve shared a posterior papillary muscle in the left ventricle with the posterior mitral leaflet, division of this papillary muscle was thought to induce papillary muscle dysfunction of both leaflet. Hence, the chordae of straddling tricuspid leaflet was detached from the shared papillary muscle and the ventricular septal defect was closed by a large pericardial patch. Because of peculiar anatomy of the conduction system in this situation, the junctional area of the inlet septum and tricuspid annulus was avoided from stitching in VSD closure. Suture through the tricuspid septal leaflet and pericardial patch for VSD were used for tricuspid valve replacement as well. The patient showed uneventful postoperative course without any conduction disturbance including the right bundle branch block. PMID- 2600483 TI - [A case report of early valve replacement surgery in infective endocarditis with mycotic cerebral aneurysm]. AB - Mycotic cerebral aneurysm is a relatively infrequent complication of infective endocarditis. However, rupture and intra-cranial hemorrhage involves so high a mortality that few patients can be saved from this condition. We reported a 22 year-old woman with mitral regurgitation and ruptured mycotic cerebral aneurysm caused by infective endocarditis. Vegetation floating between the left atrium and the ventricle was observed by UCG. It was difficult to decide which operation should be done first, valve replacement or excision of cerebral aneurysm. To avoid further intracerebral bleeding caused by anticoagulant therapy connected with cardiotomy, the cerebral aneurysm was excised prior to the valve replacement. Mitral valve was replaced with a Bjork-Shiley prosthetic valve 48 hours after the craniotomy. The postoperative course was uneventful and no neurological deficit was found. This report indicates that valve replacement surgery can be successfully performed only 48 hours after craniotomy without any bleeding complications. PMID- 2600485 TI - [Mitral regurgitation due to anomalous attachment of chordae tendineae to the left atrial wall]. AB - A 47-year-old female admitted to our hospital with exertional dyspnea and cerebral thromboembolism. There was no history of rheumatic fever. The chest roentgenogram showed marked cardiomegaly with pulmonary congestion. Ultrasound cardiogram showed mitral valve incompetence and abnormal echo shadow in the left atrium. Left ventriculogram revealed grade 3 mitral regurgitation. At operation, a 5-cm anomalous chordae tendineae was attached to the left atrial wall through the mitral orifice. The mitral valve showed thickening of the leaflets and fusion of the posterior commissure. The mitral valve was replaced with a mechanical prosthesis. The patient has been doing well after her surgery. PMID- 2600486 TI - [Three-dimensional structure and function of epidermal growth factor]. PMID- 2600487 TI - [Structure and function of perforin]. PMID- 2600488 TI - [Improved detection of macromolecular proteins with sodium dodecyl sulfate polyacrylamide slab gel electrophoresis]. PMID- 2600489 TI - Maxillomandibular relationships in patients with dentofacial deformities: diagnostic criteria utilizing three cephalometric analyses. AB - This paper evaluates the quantitative and qualitative diagnostic criteria utilizing three cephalometric assessments of the maxillomandibular relationship. Evaluation was applied to pretreatment and posttreatment cephalometric radiographs of 13 patients with dentofacial deformities that were corrected by combined orthodontic-surgical treatment with good esthetic and functional results. These evaluations were analyzed individually and compared to one another and with the type of surgery performed. Results indicate that (1) dentoskeletal discrepancy cases need evaluations in addition to conventional celphalometric analysis; (2) the evaluation based on SNA, SNB, and ANB angles is not reliable when there is an alteration in the lower one-third facial height; (3) the Wits appraisal shows good reading capacity but must be supplemented by additional analyses, because it does not differentiate the precise location origin of the deformities; (4) the McNamara analysis shows higher correlation between the actual surgical corrections performed, when the nasolabial angle is considered a primary guide to evaluate the position of the maxilla; and (5) notwithstanding the diagnostic capacity of the McNamara analysis, it has a definite tendency to present discrepancy values larger than would be inferred from the correction adopted by the surgeon, with the exception of mandibular advancement in cases of Class II with mandibular retrusion. PMID- 2600490 TI - Titanium mesh rigid internal fixation of the modified LeFort III osteotomy. AB - Surgical techniques for correcting midfacial deformities have used bone grafting with direct wire fixation, occlusal overcorrection, and maxillomandibular fixation for 6 to 8 weeks. With the advent of rigid internal fixation, the need for occlusal overcorrection and maxillomandibular fixation has been reduced or eliminated. A technique of rigid internal fixation using titanium mesh is presented. Two representative cases and their 18-month followups are described. PMID- 2600491 TI - Concerns, motivation, and experience of orthognathic surgery patients: a retrospective study of 152 patients. AB - Patient perceptions and motivations for undergoing orthognathic surgery were evaluated retrospectively by a 15-item self-administered questionnaire. Surgical risk was the major reservation concerning having an operation, and change in appearance and cost of treatment were of next greatest concern. Of the 152 patients, 78.3% would elect to have surgery again. Female patients desired improvement in appearance more than male patients. PMID- 2600492 TI - Temporomandibular joint fibrous ankylosis following orthognathic surgery: report of eight cases. AB - Undue pressure on the temporomandibular joint consequent to orthognathic surgery may result in fibrous ankylosis in the joint. Occurrence of this disorder may increase with the use of rigid internal fixation combined with 6 to 8 weeks of maxillomandibular fixation. Proper intraoperative placement of the proximal mandibular segment is the key to prevention of this complication, especially in high-risk joints. PMID- 2600494 TI - [Recent trend in the research of hyperlipidemia in Japan. Secondary hyperlipoproteinemia]. PMID- 2600493 TI - [Recent trend in the research of hyperlipidemia in Japan (1). Profiles of primary hyperlipidemia]. PMID- 2600495 TI - [Recent trend in the research of hyperlipidemia in Japan (2). Molecular genetics and clinical features of familial hypercholesterolemia]. PMID- 2600496 TI - [Recent trend in the research of hyperlipidemia in Japan. Three mutations including two deletions of the low density lipoprotein receptor gene in Japanese patients with homozygous familial hypercholesterolemia]. PMID- 2600497 TI - [Recent trend in the research of hyperlipidemia in Japan. Influence of defective metabolism of low-density lipoprotein on atherosclerosis]. PMID- 2600498 TI - [Recent trend in the research of hyperlipidemia in Japan (3). Apolipoprotein E polymorphism and hyperlipoproteinemia]. PMID- 2600499 TI - [Recent trend in the research of hyperlipidemia in Japan. Significant role of apo E in lipoprotein metabolism in rabbits]. PMID- 2600500 TI - [Recent trend in the research of hyperlipidemia in Japan. Physical exercise in the treatment of hyperlipidemia]. PMID- 2600501 TI - [Recent trend in the research of hyperlipidemia in Japan. Problems in dietary treatment of hyperlipoproteinemia]. PMID- 2600502 TI - [Primary biliary cirrhosis]. PMID- 2600503 TI - [Current status and problems in digitalis therapy]. PMID- 2600504 TI - [Changes in serum CK and GOT concentration as a noninvasive marker of restoration of infarct-related coronary artery]. PMID- 2600505 TI - [Comparison of auscultation, M-mode echocardiography and color Doppler for detecting aortic regurgitation in patients without mitral stenosis]. PMID- 2600506 TI - [Restless leg syndrome associated with syphilitic meningitis: a case report]. PMID- 2600507 TI - [Preoperative diagnosis of a case of biliobiliary fistula]. PMID- 2600508 TI - [A case of anomalous origin of the right coronary artery from the left coronary sinus of Valsalva]. PMID- 2600509 TI - [A case of central sleep apnea syndromes and tachypnea at awake time due to arteriosclerotic changes in right vertebral artery]. PMID- 2600510 TI - [A case of pernicious anemia associated with early gastric cancer (Type IIa + IIc) and squamous cell carcinoma of the oral mucosa]. PMID- 2600511 TI - [A case of Turner's syndrome with ulcerative colitis]. PMID- 2600512 TI - [A case of the right atrium-originating hemangiosarcoma manifested by cardiac tamponade]. PMID- 2600513 TI - [An investigation on the oral surgery patients and their treatments]. AB - The author has studied on the various diseases occurring in the oral and maxillofacial region for the year of 1987 at the Department of Oral & Maxillofacial Surgery, Seoul National University Hospital. The diseases diagnosed and treated have been analyzed according to each disease such as inflammatory, traumatic, cyst, tumor, neoplastic, deformities and so on, in order to get accurate information on the diseases of the oral & maxillofacial region and the information might be helpful to plan the education programmes for students, and interns and residents. The results obtained are as follows; 1. The sex distinction and the percentage of occurrence rate as follow Male 2090 (49.6%) Female 2127 (50.4%) 2. To study compare with the age, both male and female patients showed the highest ratio at the 20-29 age group, and the percentage of the 20-49 age group is 64.1% and the percentage of geriatric patients over 60 years old is 10.2%. 3. To study compare with the month (the patient came first time), August was most abundant in a year. 4. To study compare with the disease, dental-periodontal disease, impacted tooth and eruption abnormality are the most prevalent (51.2%), and next is odontogenic infection (22.4%), cyst & tumor (7.6%), traumatic injury (7.5%), and anomaly or deformity (3.8%). The number of medically compromised patients with oral surgery problems is 183 (4.3%). 5. Classifying the treatments according to the operator group, 1) For students(senior class), simple extraction showed the highest ratio, next is surgical extraction. 2) For interns, simple extraction showed the highest ratio, next is surgical extraction, pre-prosthetic surgery (alveoloplasty and vestibuloplasty).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600514 TI - [A study on the reliability of EMG examination using EM2]. AB - This study was performed to investigate the reliability of EM2 (Myotronics research Inc.). Two dentists as examiners took part in the study and examined 21 dental students, Seoul National University, respectively and repeatedly. Strong correlations could be found between the results of examinations. Conclusively, it is believed that the use of EM2 could be an electrodiagnostic modality for diagnosis and evaluation for the activity of masticatory muscles. PMID- 2600515 TI - [Tricalcium phosphate implant in periodontal defects--initial 3 months]. AB - The present study was performed to evaluate the effect of tricalcium phosphate implant in human osseous defects. 4 intraosseous defects in 2 patients were treated with mucoperiosteal flap and tricalcium phosphate (TCP) implant and another 5 defects in the same patients were debrided only via mucoperiosteal flap. The healing response was evaluated clinically 10-12 weeks after treatment. More reduction in probing depth and more gains in probing attachment levels were observed in implanted sites than in control sites. PMID- 2600516 TI - An experimental study of the effects of light exposure time on the depth of curing of composite resin. PMID- 2600517 TI - [The effect of composition on the mechanical properties of composite resin]. AB - The objective of this investigation was to determine whether the composition of composite resin affects the amount of residual monomers and the strength of resin. Six types of resin composition were designed and 30 composite resin specimens were made in glass mold of 6mm diameter and 3mm height. The residual monomer of each specimen was extracted by 10cc ethanol solution for 1, 2, and 3 days of experiment. UV/Vis spectrophotometer was used to estimate the amount of residual monomer of the specimen, and universal testing machine was used to test the diametral tensile strength of the composite resin. The results were as follow; 1. Composite resins of 1% benzoyl peroxide concentration released the higher level of residual monomers than the resin of 0.8% benzoyl peroxide concentration. 2. t-Butylaminoethylmethacrylate.HF of 17% concentration exhibited the greater level of residual monomer than the other resin monomers. 3. As the concentration of the trimethylolpropane trimethacrylate increased, the amount of Bis-GMA residual monomer increased. 4. Composite resin of 1% benzoyl peroxide concentration showed higher tensile strength than the resin of 0.8% benzoyl peroxide concentration. 5. As the concentration of trimethylolpropane trimethacrylate increased above 50%, the strength of the composite resin decreased. PMID- 2600518 TI - [The relation of pericoronitis to the position of the mandibular third molar]. AB - Pericoronitis is the most commonly encountered pathologic condition involving the mandibular third molar. Because of the dangers associated with mandibular third molar pericoronitis, prophylactic extraction of third molar at high risk has been recommended. We studied 411 patients with mandibular third molar pericoronitis by clinical symptoms and radiographic measurement of mandibular third molar height, wideth and angulation. The results were as follows: 1. Mandibular third molar pericoronitis is frequently seen in third decade and there are no sexual difference significantely. 2. In inflammatory type of mandibular third molar pericoronitis, chronic pericoronitis occured more frequently than acute type. 3. In relation to angulation and height, mandibular third molar most likely to be afflicted with pericoronitis is vertical eruption at occlusal plane of the second molar. 4. In relation to angulation and width, it appears that the position of the mandibular third molar most likely to be afflicted with pericoronitis is in a vertically erupted tooth of which the space between the ramus and the distal side of the second molar is less than the mesiodistal diameter of crown. (Class II). 5. In relation to height and width, it appears that the position of the mandibular third molar most likely to be afflicted with pericoronitis is class II width (described above)at occlusal plane of the second molar. PMID- 2600519 TI - [The changes of the orofacial muscle activity induced by the lip forces in subjects with normal occlusion]. AB - This study was intended to investigate whether lip exercise affect the activities of the lips, tongue, digastric and masseter muscles and to understand the functional interrelationship between them. As the forces of maximum lip grimace was reduced to slight lip seal gradually, the electromyograph was taken from 9 conscious human adults with normal occlusion in the upper and lower lips, tongue, digastric and masseter muscle using surface electrodes, especially, newly designed subminiature surface electrodes which was attached directly to the tongue. The results were as follows. 1. During induced maximum lip grimace in the mandibular rest position, there're prominent increase of EMG activity in the upper and lower lips, tongue and digastric muscle 1714 mu v, 2787 mu v, 2142 mu v and 623 mu v, respectively, but there was little activity in the masseter muscle, 129 mu v. The force level induced by maximum grimace of the lips was about 110g when the force transducer was positioned between upper and lower lips in the incisor area. 2. As the lip forces were reduced gradually, EMG activities of the lips, tongue and digastric muscles were decreased definitely with certain tendency, but there was no change in the masseteric EMG activity. Above mentioned results suggest that (1) lip exercise can promote the activities of the lips, tongue and digastric muscles but cannot change the activity of the masseter muscle and (2) masseteric muscle activity seems to be independent of the lips and the tongue but digastric muscle activity is related more closely to them through lip exercise in the subjects with normal occlusion. PMID- 2600520 TI - [A case report of odontogenic infection leading to fatal mediastinitis]. AB - Mediastinitis can be life-threatening complication of oral and maxillofacial surgery. Mediastinitis from odontogenic deep cervical infection is extremely rare in the era of antibiotic drugs. Such complication is subjected to the ravages of a gas-forming anaerobic infection. We have encountered such a case, with a rapid spread of the inflammatory process into the mediastinum resulting in a number of local and systemic complications. The submandibular fascial spaces served as a pathway for the propagation of an overwhelming infection along cervical planes in a posterior direction to the lateral pharyngeal spaces and then to the retropharyngeal spaces, the mediastinum. Despite massive antibiotic therapy, general supportive care and surgical drainage, the patient died. PMID- 2600521 TI - [A pathological consideration of ankyloglossia and lingual myoplasty]. AB - Despite the curious role of tongue in the development of oro-facial structures the tongue remains as rather quiescent organ without bony skeleton. But it is said that neuro-muscular complex of tongue is important in the developmental and functional process. Ankyloglossia and macroglossia are occasionally implicated in the oral diseases. Many authors supposed that the ankyloglossia and macroglossia might produce various abnormal oro-facial growth, such as bimaxillary or mandibular protrusion and anterior open bite, etc. We have designed the classification of ankyloglossia by measuring the median lingual frenum length with lingual frenum ruler. It is well known that every people has a lingual frenum to some degree. So we analyse that the group showing less than 10mm of median frenum length is belong to mild ankyloglossia, the group showing from 10mm to 15mm of median frenum length is belong to moderate ankyloglossia, the group showing more than 15mm of median frenum length is belong to type 1 severe ankyloglossia, and the group showing clinically severe ankyloglossia but having less than 15mm of median frenum length is belong to type 2 severe ankyloglossia. We have experienced that the mild ankyloglossia usually causes no clinical complication to receive dental treatments. In the present study we investigated different clinical complications under this classification. We also recognized that the most retracted tongue position is a comparable criterion of tongue movement. The severer ankyloglossia showing thick lingual frenum is the more frequently associated with macroglossia and occlusal disharmony, and its most retracted tongue position is prone to locate high-anterior direction. Among 130 cases receiving lingual myoplasty 106 cases (81.5%) showed various malocclusions, 37 cases (28.5%) showed conspicuous speech problem, and 14 cases (19.8%) showed severe oro-facial deformity. The lingual myoplasty consists of two steps, the first is the same with frenectomy, and the second is the procedure of re equilibrium of extrinsic tongue muscles mainly between genioglossus muscle and hyoglossus muscle. 130 cases which were belong to the group of moderate and severe ankyloglossia were selected for the lingual myoplasty, and the patients were ordered to keep on self training by the method of Dr. Lim's tongue movement. In three months after lingual myoplasty there was no relapse of ankyloglossia and the most retracted tongue position changed to inferior and posterior direction effectively (Tab. 6, 7, 8), and on gross finding the size of tongue seems to be decreased.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600522 TI - [Clinical studies on oral infections in the oral cavity and maxillofacial regions]. AB - The author has undertaken clinical studies on oral infections in the oral cavity and maxillofacial regions by analyzing 987 patients with infections among 3,921 in-patients hospitalized in the Department of Oral and Maxillofacial Surgery, Seoul National University Hospital past 7 years from 1980 to 1987. The results obtained were as follows: 1. Oral infection as inflammatory disease in dentistry is still very important disease occupying 25.4% of diseases in oral and maxillofacial regions. 2. The high 3 top inflammatory diseases in the department of oral and maxillofacial surgery admitted were odontogenic maxillary sinusitis (37.6%), osteomyelitis (29.1%), and abscess (22.2%) among 14 kinds of oral infections. 3. Anaerobic bacterial infections tend to be increasing since new developed bacterial culture chamber has been used. PMID- 2600523 TI - Temporal bone fractures. AB - Temporal bone fractures represent a frequent source of morbidity and are often associated with fatal injuries in the head trauma patient. The initial care of these patients may be the responsibility of the emergency room physician or the neurosurgeon. The treatment of temporal bone fractures is often postponed because more pressing injuries may exist. However, it should be stressed that an otolaryngologist be consulted as soon as feasible because future rehabilitation is dependent on the initial examination. PMID- 2600524 TI - A case of Strongyloides stercoralis in central Louisiana. AB - A typical case of Strongyloides stercoralis in a nonimmunocompromised host is described in which the diagnosis was made only by examination of purged stools. Strongyloides stercoralis probably occurs in 3% to 5% of patients in the rural south. It also occurs in selected populations of southeast Asian immigrants and American veterans of war in the Far East. Because of its capacity for reinfection, unusually long infestations can occur. Hyperinfections, with 50% mortality, may occur in iatrogenically or naturally immunocompromised patients. Consequently, a high index of suspicion, coupled with aggressive persistence in obtaining stool samples, is necessary for timely recognition and treatment of this potentially fatal disorder. PMID- 2600525 TI - Update on the management of glaucoma. AB - Most cases of chronic open-angle glaucoma can be treated medically. When medical management is ineffective, laser trabeculoplasty is usually performed. If medical management and laser treatment fail, surgery is the next step. Recently, ultrasound has been employed successfully for control of glaucoma when medical, laser, and surgical treatments were not successful. Acute angle-closure glaucoma is an ophthalmic emergency. This condition can be treated at an early stage by relieving the pupillary block with peripheral iridectomy by laser or surgery. Four major classes of drugs are currently used to treat glaucoma: carbonic anhydrase inhibitors, beta adrenergic blockers, parasympathomimetics, and sympathomimetics. Both local and systemic side effects may occur secondary to glaucoma medications and some of these may be severe or even fatal. These adverse reactions are discussed. PMID- 2600526 TI - ECG of the month. On the right track. Complete left bundle branch block. PMID- 2600527 TI - "Changing times"--a professional woman's viewpoint. PMID- 2600528 TI - Implantology--how to maintain our success. PMID- 2600529 TI - Considerations in management of odontogenic infections. PMID- 2600530 TI - The benefit of radiographs in endodontics. PMID- 2600531 TI - Regeneration of lost periodontal tissues using citric acid and fibronectin. PMID- 2600532 TI - Effectiveness of mouthrinses. PMID- 2600534 TI - Current concepts of occlusion. PMID- 2600533 TI - Infection control: how far have we come ... how much farther do we have to go?. Interview by Annette Skowronski. PMID- 2600535 TI - Trauma from occlusion and periodontal disease. PMID- 2600536 TI - Temporomandibular joint diagnosis. PMID- 2600537 TI - TM therapy: avoiding legal pitfalls. PMID- 2600538 TI - Relationships between LDL density and kinetic heterogeneity in subjects with normolipidemia and familial combined hyperlipidemia using density gradient ultracentrifugation. AB - The metabolism of heterogeneous subpopulations of low density lipoprotein (LDL) apoB100 was examined in three normolipidemic and two familial combined hyperlipidemic subjects. Autologous radioiodinated plasma LDL (1.019 less than d less than 1.063 g/ml) were injected into each subject and the disappearance and appearance of radiolabeled lipoproteins into various LDL subpopulations were examined using density gradient ultracentrifugation. Eleven to 13 fractions (-320 microliter each) were collected within LDL defined uniquely in each subject. In all subjects, the disappearance of radiolabeled LDL from plasma was biexponential. However, changes with time in the distribution of radiolabeled LDL among the various LDL density subpopulations revealed complex metabolic behavior that differed among the subjects. When the relationships between density and kinetic characteristics were examined in more detail by following the disappearance of individual fractions defining LDL in each subject, the data suggested that: 1) the kinetic behavior of the LDL fractions was more complex than suggested by the disappearance of radiolabeled LDL from plasma: 2) certain fractions within specific density ranges were kinetically similar; 3) distinct differences in the disappearance curves among the fractions occurred within narrow density ranges; and 4) precursor-product relationships were seen among specific LDL density fractions and varied from subject to subject. These studies underscore the complexities of plasma LDL apoB-100 metabolism. More detailed characterizations of the kinetic behavior of various LDL subpopulations should help in our understanding of the origin(s) and potential physiological consequences of different LDL subpopulations. PMID- 2600539 TI - Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis. AB - We measured the turnover and absorption of sitosterol and cholesterol, along with plasma sterol and lipoprotein concentrations, in one control and two subjects with sitosterolemia with xanthomatosis. All individuals consumed the same diet which contained approximately 500 mg/day of cholesterol and 250 mg/day of sitosterol. Sterol absorption was measured by the plasma dual-isotope ratio method and turnover by plasma isotope-kinetic analysis. In two sitosterolemic subjects, 28% and 63% of the sitosterol and 69% and 49% of the cholesterol were absorbed, respectively, compared to 4% of the sitosterol and 44% of the cholesterol in the control. As expected, plasma sitosterol specific activities decayed much more rapidly than cholesterol in the control subject. In contrast, plasma sitosterol and cholesterol specific activity-time curves were similar and decayed more slowly in the sitosterolemic subjects. In the control subject, the total sitotterol pool was 290 mg and was linearly related to low absorption (18 mg/day); whereas the total sitosterol pool was 17 times (4800 mg) and 13 times (3500 mg) larger, respectively, in the sitosterolemic subjects and was expanded out of proportion to increased absorption because of decreased removal. Daily cholesterol turnover and synthesis were markedly reduced in the sitosterolemic subjects. In four sitosterolemic subjects, plasma concentrations of total sterols, low density lipoproteins, and apolipoprotein B were increased, while those of high density lipoproteins and apolipoprotein A-I were low to normal. The low density lipoproteins were very similar to those of normal control subjects in density distribution, peak flotation rate, sterol-to-protein (apolipoprotein B) ratio, particle size, and morphology. These results demonstrate in patients with sitosterolemia with xanthomatosis that: 1) the absorption of sitosterol and cholesterol is enhanced; 2) tissue recognition between cholesterol and sitosterol is lost; 3) total exchangeable sitosterol pools are expanded out of proportion to absorption because of decreased excretion; 4) plasma sterol and lipoprotein concentrations favor tissue deposition; and 5) cholesterol synthesis is diminished. We postulate that the changes in sitosterol metabolism (increased absorption, loss of tissue sterol structural recognition, expanded pools, and hepatic retention) are a response to reduced cholesterol synthesis in these subject. PMID- 2600540 TI - Genetic studies of human apolipoproteins. XI. The effect of the apolipoprotein C II polymorphism on lipoprotein levels in Nigerian blacks. AB - The human apolipoprotein C-II locus exhibits genetically determined structural polymorphism in United States and African blacks. In the present study, we have investigated the effect of the apoC-II polymorphism on quantitative serum levels of total cholesterol, total high density lipoprotein (HDL) cholesterol, cholesterol in high density lipoprotein subfractions, low density lipoprotein (LDL) cholesterol, and triglycerides (TG) in a sample of 368 unrelated Nigerian blacks. The frequencies of the APOC-II*1 and APOC-II*2 alleles in the samples were 0.947 and 0.053, respectively. In males, the effect of the APOC-II*2 allele was to lower the total serum cholesterol and LDL-cholesterol levels by 13.28 mg/dl and 10.55 mg/dl, respectively, relative to the common allele, APOC-II*1. In females, the effect was to lower total plasma cholesterol by 4.49 mg/dl and LDL cholesterol by 3.21 mg/dl. The effect of apoC-II on quantitative lipoprotein levels is shown to be independent of variation at the linked apoE locus, but the products of the two loci interact in determining overall quantitative phenotypes. PMID- 2600541 TI - Cholesterol transfer from mitochondrial membranes and cells to human and rat serum lipoprotein fractions. AB - We have investigated the transfer of [14C]cholesterol from labeled bovine heart mitochondria and Friend erythroleukemic cells to high density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) fractions from human and rat plasma. The lipoprotein fractions were obtained by molecular sieve chromatography of plasma on agarose A-5m columns. For either membrane system, the highest rate of [14C]cholesterol transfer was observed with the human and the rat HDL fraction. Since the mitochondria lack the receptors for HDL, one may conclude that the observed preferential transfer is not governed by a receptor-controlled interaction of HDL with the membrane. Under conditions where the pool of free cholesterol in the lipoprotein fractions was the same, HDL was a much more efficient acceptor of [14C]cholesterol from mitochondria than LDL or VLDL. Similarly, transfer of [14C]cholesterol proceeded at a higher rate to HDL than to sonicated egg phosphatidylcholine (PC) vesicles, even under conditions where there was a tenfold excess of the vesicle-PC pool over the HDL phospholipid pool. This preferred transfer of [14C]cholesterol to HDL cannot be explained by a random diffusion of monomer cholesterol molecules. Rather, it shows that HDL has a specific effect on this process in the sense that it most likely enhances the efflux of cholesterol from the membrane. Treatment of HDL with trypsin reduced the rate of [14C]cholesterol transfer by 40-50%, indicating that protein component(s) are involved. One of these components appears to be apoA-I, as this protein was shown to enhance the transfer of [14C]cholesterol from mitochondria to lipid vesicles. PMID- 2600542 TI - Formation of crystalline tripalmitin-rich spicules in isolated hepatocytes. AB - Conditions were developed for rapid deposition of triglyceride in isolated rat hepatocytes. Liver cells from fasted rats were incubated for 90 min at 37 degrees C with 3.0 mM palmitic or oleic acid, 4% bovine serum albumin, 20 mM glucose, 10 mM lactate, and 1 mM pyruvate. When oleic acid was used, numerous cytoplasmic lipid droplets were produced. When hepatocytes were incubated with palmitic acid, similar amounts of triglyceride were synthesized but instead of lipid droplets, a vast accumulation of peculiar spicules permeated the cytoplasm. These inclusions appeared in myriads of swirled threads, thick elongated angular plates, and needles, some of which exhibited longitudinal osmiophilic bands of 250 A thickness. These structures were associated with smooth endoplasmic reticulum. The cells appeared otherwise normal. Polarized light microscopy at 37 degrees C revealed a multiplicity of brilliant white inclusions between crossed polars in cells incubated with palmitic acid. These birefringent structures exhibited 90 degrees periodicity between both maximum brilliance and extinction, indicative of anisotropic crystalline deposits. Molecular species analysis of triglycerides in cells incubated with palmitic acid, together with data on [1-14C]palmitic acid incorporation, demonstrated an almost exclusive synthesis of tripalmitin. Spicules isolated from homogenized hepatocytes displayed needles containing longitudinal single and double osmiophilic bands of 110 A and 260 A thickness, respectively, and lipid spicular aggregates. The isolated spicules were almost pure tripalmitin by analysis. These observations document the formation and development of crystalline triglyceride in living cells and may provide a unique system for the study of cellular lipid synthesis, transport and deposition. PMID- 2600543 TI - Cholesteryl oleyl and linoleyl ethers do not trace their ester counterparts in animals with plasma cholesteryl ester transfer activity. AB - Cholesteryl ethers are nonhydrolyzable tracers of cholesteryl esters. We report here that the ethers are not legitimate tracers of esters in systems involving plasma cholesteryl ester transfer activity. On intravenous injection of doubly labeled high density lipoproteins into rabbits, cholesteryl ester tracer was more rapidly transferred to other lipoprotein fractions than was cholesteryl ether tracer. In direct assays in vitro, the rate of transfer of esters was about two times that of the ether. This difference was not due to tracer impurity or lability of 3H, did not depend on the nature of the donor or acceptor lipoprotein, and was similar for cholesteryl ester transfer activities of both human and rabbit origin. PMID- 2600544 TI - A novel sterol-regulated surface protein on chicken fibroblasts. AB - In the laying hen, two different receptors for apolipoprotein B (apoB)-containing lipoproteins are expressed on somatic cells and oocytes, respectively. The somatic protein has an apparent Mr of 130,000, while the oocyte receptor is a 95 kDa protein (1989. K. Hayashi, J. Nimpf, and W. J. Schneider, J. Biol. Chem. 264:3131-3139). In order to investigate the yet unresolved relationship between these two proteins, we applied immunoblotting with anti-receptor antibodies to extracts of oocytes and chicken embryo fibroblasts. IgG fractions that recognize the 95-kDa oocyte receptor did not cross-react with the somatic receptor; however, chicken fibroblasts as well as ovarian granulosa cells that had been exposed to sterols (cholesterol and 25-OH-cholesterol) or low density lipoprotein (LDL) were shown to express a novel immunoreactive protein with an apparent Mr of 110,000. This protein is localized on the cell surface, and is unable to bind apoB-containing lipoproteins. The formation of the 110-kDa protein in fibroblasts is induced in time- and concentration-dependent fashion by sterols, concomitant with a progressive decrease in the amount of functional 130-kDa receptor protein. Following its induction, exposure of cells to LDL, but not to high density lipoprotein, caused the disappearance of the immunoreactive protein. Furthermore, the production of the 110-kDa protein did not require protein synthesis. These data are compatible with the notion that this novel receptor-related, nonfunctional protein is a truncated intermediate in the degradation pathway for the 130-kDa apoB receptor, and that the truncation generates antigenic epitope(s) shared by the 95-kDa oocyte receptor and the 110-kDa protein, but not expressed on the somatic receptor. PMID- 2600545 TI - Evaluation of a monoclonal antibody-based enzyme-linked immunosorbent assay as a candidate reference method for the measurement of apolipoprotein B-100. AB - A monoclonal antibody-based direct binding enzyme-linked immunosorbent assay (ELISA) for apoprotein (apo) B-100 has been developed for use as a reference method. The assay uses the two well-characterized monoclonal antibodies, MB24 and MB47. MB47, which recognizes an epitope at the low density lipoprotein (LDL) receptor-binding domain of apoB and is specific for apoB-100, is bound to the microtiter plate as the capture antibody. MB24, which binds an epitope in the amino terminal half of the apoB-100 and identifies both apoB-100 and apoB-48, is conjugated to horseradish peroxidase and is utilized as the indicating antibody. The assay was calibrated with LDL (d 1.030-1.050 g/ml) and the LDL protein was determined by a sodium dodecyl sulfate (SDS) Lowry procedure. The working range of the assay is 0.25-1.25 micrograms/ml. Optimal dilution of whole plasma was found to be 1:2000. In the assay, MB47 bound approximately 97% of the apoB in all low density lipoprotein, and greater than 90% of the apoB in the majority of very low density lipoprotein preparations. Small dense LDL from subjects with familial combined hyperlipidemia (FCHL) and large bouyant LDL from subjects with familial hypercholesterolemia (FH) exhibited binding properties similar to LDL from healthy normolipidemic subjects when tested in the reference ELISA. The intra- and interassay coefficients of variation averaged 2.5% and 6.0%, respectively. Plasma B-100 levels were not influenced by freezing and thawing or storage at 4 degrees C for up to 3 weeks or storage at -70 degrees C for up to 11 months. Excellent agreement was obtained between the reference ELISA and a polyclonal RIA which measures total apoB (r = 0.93, n = 105, mean ELISA B-100 value = 100 mg/dl, mean RIA value = 101 mg/dl, Sy = 9.6). Reference ELISA B-100 values of samples pretreated with bacterial lipase were not significantly increased in most samples with plasma triglyceride levels below 600 mg/dl. To help reduce the large among laboratories variability of apoB measurements, we recommend that this candidate reference direct binding ELISA be used to assign apoB target values to apoB reference pools. PMID- 2600546 TI - Thermospray ionization liquid chromatography-mass spectrometry: a new and highly specific technique for the analysis of bile acids. AB - A rapid, highly specific and sensitive combined high performance liquid chromatography-mass spectrometric (LC-MS) method is described for the analysis of bile acids in biological fluids. Ionization of polar bile acid conjugates is achieved in the thermospray interface that is used to directly couple the LC column to the mass spectrometer, thereby allowing continuous monitoring of the LC effluent. Maximum sensitivity (4-10 pmol) is achieved by recording the negative ions generated in the ionization process and mass spectra obtained for the principal bile acid conjugates are characterized by intense [M-H]-pseudo molecular ions and fragment ions due to consecutive losses of water corresponding to a number of hydroxyl groups in the molecule. The mass spectrometer thus provides molecular weight and useful structural information for each compound separated by HPLC. Applications of the LC-MS technique to the analysis of bile acids in bile and serum samples after an initial solid-phase extraction step highlight the potential of the thermospray interface for enhancing the specificity and sensitivity of the HPLC technique for bile acid analysis. PMID- 2600547 TI - Silver ion chromatography using solid-phase extraction columns packed with a bonded-sulfonic acid phase. AB - Commercial solid-phase extraction columns packed with a stationary phase with bonded benzenesulfonic acid groups are readily converted to the silver ion form and can then be used for silver ion chromatography of lipids. To illustrate the utility of such procedures, methyl ester derivatives of fatty acids with zero to six double bonds were separated from each other by a simple stepwise elution scheme. -Christie, W. W. Silver ion chromatography using solid-phase extraction columns packed with a bonded-sulfonic acid phase. PMID- 2600548 TI - Bilateral mandibular dental anomaly. PMID- 2600549 TI - A clinico-pathologic presentation. PMID- 2600550 TI - Biochemical diagnosis of an hereditary aminolaevulinate dehydratase deficiency in a 63-year-old man. AB - Porphyrin metabolism was investigated in a 63-year-old male patient who developed a subacute onset polyneuropathy with predominance of motor signs in the upper limb. The screening for lead, cadmium, mercury, aluminum and thallium was negative. The study of porphyrin metabolism showed remarkable abnormalities, particularly a very high level of plasmatic 5-aminolaevulinic acid contrasting with a normal level of porphobilinogen and a nearly complete loss of activity of aminolaevulinic acid dehydratase with no regenerative response to dithiothreitol or zinc ions. The other causes of aminolaevulinic acid dehydratase deficiency (tyrosinaemia, alcoholism, smoking, cirrhosis, renal insufficiency, diabetes mellitus) were ruled out. The diagnosis of primary aminolaevulinic acid dehydratase deficiency was proposed and confirmed by the familial study, which revealed the existence of several heterozygous members in this family. PMID- 2600551 TI - Serum isoenzyme pattern of creatine kinase and lactate dehydrogenase in various animal species. AB - The creatine kinase and lactate dehydrogenase isoenzyme pattern were determined in the serum of normal and untreated rats, rabbits, dogs, monkeys and pigs. The relative distribution of all isoenzymes in the serum and an electrophoretic pattern for each animal species are presented. The isoenzyme serum pattern showed a great variation between the species. The diagnostic value of serum creatine kinase isoenzyme MB and lactate dehydrogenase isoenzymes 1 and 2 in predicting cardiac lesions in different animal species is briefly discussed. PMID- 2600552 TI - Development and validation of a radioimmunoassay for serum melatonin. AB - A radioimmunoassay using N-[3-(4-hydroxy-3-[4-hydroxy-3- [125I]iodophenylpropionyl)]-5-methoxytryptamine as tracer for determination of melatonin in the serum of different species is described. Melatonin antisera were raised in rabbits by immunization with a bovine serum albumin conjugate of N-[3 (2-aminoethyl)-5-methoxy indole] hemisuccinamide. A single high affinity, specific antiserum was obtained. In contrast to previous studies, the tracer was synthesised in one step in the absence of water, giving an excellent yield of highly pure product. No chromatographic purification step was needed. Polyethylene glycol in combination with goat antirabbit immunoglobulins was used to separate bound and unbound tracer. Sera were delipidized with Lipoclean prior the extraction of melatonin with diethyl ether. This sample preparation allows the determination of melatonin in the presence of widely varying amounts of lipids in human, rat and hamster serum. Using this extraction procedure, the sensitivity of the radioimmunoassay was approximately 1 ng/l of serum. Dilutions of sera and of synthetic melatonin gave the same parallel response in the radioimmunoassay. High performance liquid chromatography analysis of a serum extract showed only one immunoreactive peak co-eluting with synthetic melatonin. Characteristic diurnal rhythms of melatonin were observed in all species. All assay components including standards and serum controls are stable for at least 1 year at 4 degrees C, thus facilitating the determination of melatonin in a routine laboratory. PMID- 2600553 TI - Sound speed, density and total protein concentration of blood. AB - The sound speed and the density of a series of blood samples was measured in a temperature range from 20 degrees C to 40 degrees C. An expression was derived from a least square fit which related the sound speed in human blood in this temperature range to the blood density and to the total protein concentration, respectively. The data were obtained from the measurement of sound speed and density by means of a newly developed Density and Sound Analyzer (DSA-48, A. Paar K.G., 8054 Graz, Austria). The relationship of sound speed, density and temperature permits the calculation of the total protein concentration with an accuracy of 1 g/kg. The resolution of the measurement is in the order of 0.1 g/kg. PMID- 2600554 TI - Improved method for enzymic determination of cholesterol in lipoproteins separated by electrophoresis on thin layer agarose gels. AB - The cholesterol of lipoproteins, separated electrophoretically on thin layer agarose films, is visualised and quantitated by incubating the gels in an enzymic reagent containing cholesterol esterase and cholesterol dehydrogenase. The individual fractions are quantitated by scanning densitometry. No sample pretreatment is necessary. All major fractions are detected readily. The accuracy of the determination is similar to that of ultracentrifugation. On average, imprecision is 3.1% for beta-, 7.0% for pre beta-, and 4.8% for alpha-lipoprotein cholesterol. Concentration and colour development are linear up to 8 mmol/l cholesterol in a given lipoprotein fraction. The results from the direct enzymic procedure for beta-, pre beta- and alpha-lipoprotein cholesterol are compared with those from quantitative lipoprotein electrophoresis after precipitation with phosphotungstic acid and bivalent cations and with those from different precipitation methods using dextran sulphate and polyethylene glycol. The new method has several advantages: high specificity; lack of dependence on the actual composition of the lipoproteins; lack of interference from coprecipitated proteins in the gel, e.g. fibrinogen or paraproteins; and insensitivity to lipolysis and high free fatty acid concentrations caused by heparin application or ageing of the specimen (at least for alpha-lipoprotein cholesterol quantitation). In its convenience and simplicity of operation, and the simple calculation of results, the method is similar to standard protein electrophoresis. The proposed method is therefore suggested as a standard method for elucidating lipoprotein disorders. PMID- 2600555 TI - Influence of protein on the determination of sodium, potassium and chloride in serum by Ektachem DT 60 with the DTE module; evaluation with special attention to a possible protein error by flame atomic emission spectrometry and ion-selective electrodes; proposals to their calibration. AB - The reliability of the Ektachem DT 60 with the DTE module was evaluated. The precision of the determination of sodium, potassium and chloride in serum was adequate. The relative standard deviation for precision between days was Na+ 0.7%, K+ 1.5% and Cl- 1.0%. The means of the Ektachem results for 7 control sera differed from those of the reference method values by 0.9% (Na+), -0.9% (K+) and +4.4% (Cl-). Similar results were obtained for the analysis of patient sera. The influence of protein was investigated, using sera of increasing protein concentration prepared by ultracentrifugation. The results from the Ektachem corresponded to the values obtained by flame atomic emission spectrometry, even at high protein concentrations, although Ektachem measurements are performed by ion-selective electrodes without predilution. In paraproteinaemia, the Ektachem and flame atomic emission spectrometry results disagreed. Chloride determinations by Ektachem distinctly differed from measurements of the chloride concentration in total serum. It is proposed that ion-selective electrodes should be calibrated and linearized with respect to sodium chloride, in order to obtain an accurate value for the concentration of electrolyte in serum water. Concentrations are easier to interpret than "activities" for therapeutical purposes, and they can be used to define protein- and lipid-independent reference intervals for these electrolytes. With this calibration procedure, the results from ion-selective electrodes are never lower than values obtained by flame atomic emission spectrometry. The accuracy of ion-selective electrode measurements should be evaluated by applying reference methods for sodium, potassium and chloride to the ultracentrifugation supernatant of the corresponding serum. This approach can help to settle the dispute concerning the influence of protein on the residual liquid junction potential. PMID- 2600556 TI - Ektachem and unconjugated bilirubin measurements. PMID- 2600557 TI - Relationships between spleen and respiration in the newt. AB - Specimens of newt, Triturus cristatus carnifex (Laurenti), anesthetized by submersion in 0.2% chlorbutol in tap water for 15 min, and then placed out of water in a damp terrarium, show hypertrophy of the spleen that in 2 hr gradually increases from 0.31 +/- 0.12%with respect to body weight to 1.56 +/- 0.26% (means and standard deviation calculated for groups of six animals). Other anesthetics either do not produce hypnosis (Veronal), do not have a prolonged enough effect (ethyl ether, chloroform), or induce vasodilatation, which prevents hypertrophy (MS-222, urethane). The spleen hypertrophy, seen histologically to be due exclusively to blood congestion, is not caused by either a pharmacological effect of the chlorbutol or by the hypnotic state, as it does not appear in submerged anesthetized animals, unless the water is constantly stirred by a magnetic agitator, and can be reversed depending on the ventilation of the animal's skin. The spleen hoards blood when oxygenation is good (in air or stirred water) and releases this supply in the bloodstream when oxygenation is insufficient (in still water). The hypoxic "diffusion boundary layer," which, in still water, forms around the immobile newts, hampers respiratory exchange and stimulates the spleen contraction. This mechanism and its relationship to oxygenation has been demonstrated statistically in unanesthetized newts as well, in both air and water, despite the interference of two contrasting factors--lung respiration and spontaneous motor activity--absent in anesthesized animals. Congestion and decongestion of the spleen are the physiological mechanisms compensating for variations in the level of oxygenation, an alternative to the "capillary recruitment" described by Poczopko and Burggren and Moalli in may amphibians that appears to be absent in newts. The newt spleen, known to play a lesser role in erythropoiesis and destruction of aged erythrocytes than that traditionally assigned to it is thus of primary importance in respiration. PMID- 2600559 TI - Cellular contribution to symmetrical forelimbs from triploid-marked "polarizing region" in the embryo of axolotl, Ambystoma mexicanum. AB - Grafts of posterior tissue placed anterior to the limb bud in the salamander embryo exert a polarizing influence. To explain this result, the idea that the anteroposterior axis of the developing forelimb is polarized by a diffusible morphogen has been proposed. An alternative hypothesis, and the working hypothesis of the present study, is that the polarization of the developing salamander forelimb is accomplished by short-range cellular interactions resulting in intercalation rather than by the more global influence of a diffusible morphogen. One prediction of this intercalation hypothesis is that cells will be contributed to the limb from the "polarizing tissue." To test this idea, grafts of triploid marked polarizing tissue were implanted anterior to the limb bud in 82 diploid axolotl embryos at stages 32-34 of development. A total of 27 (33%) of the limbs that resulted were symmetrical and ranged in complexity from one to seven digits. Histological analysis of a subgroup of the original symmetrical limbs revealed that mesodermally derived tissues in the anterior side of these limbs (the side which formed as a duplication in response to the influence of the graft) contained high percentages of trinucleolate cells (muscle, 12.1%; connective tissue tissue, 12.5%; and cartilage, 13.4%) when compared to similar tissues in the posterior side of the same symmetrical limbs (muscle, 1.8%; connective tissue , 0.7%; and cartilage, 0.6%). When symmetrical limbs were amputated, 73% regenerated symmetrical limbs. When these regenerated limbs were again amputated, 63% formed symmetrical secondary regenerates. Histological analysis of the first generation of regenerated limbs revealed that the pattern of distribution of trinucleolate cells in each regenerate was similar to the pattern seen in the original symmetrical limb. These results indicate that there is considerable cellular contribution to the anterior side of the symmetrical forelimb from the mesoderm of grafted "polarizing tissue." This result supports the idea that short-range cellular interaction are sufficient for formation of symmetrical forelimbs in salamander embryos. PMID- 2600558 TI - Analysis of proteins secreted by mouse embryos developing in vivo and in vitro. AB - Proteins secreted by mouse blastocysts developing in vitro were compared to these from blastocysts developing in utero to determine if a simple medium supporting blastocyst development also supports secreted protein expression. In-vivo embryos were collected on days 3, 4, or 5 of pregnancy and incubated in 35S-methionine to produce conditioned medium containing released, labeled proteins. Embryos for culture were collected on day 3 and after 48 or 72 h labeled conditioned medium was produced. Labeled proteins were separated by two-dimensional electrophoresis and compared using a digital image analysis system. Day 3 embryos did not release proteins in detectable amounts, although synthesis of intracellular proteins was substantial. Day-4 and -5 blastocysts released proteins in increasing amount and complexity, consistent with previous results. When day-3 embryos were cultured in medium containing 4 mg/ml BSA for 48 h, secreted protein patterns were similar but not identical to those of day-5 uterine blastocysts. Although most of the proteins produced by uterine blastocysts were secreted by cultured embryos, differences were found in the relative quantities of certain proteins. Neither crystallized BSA nor polyvinyl alcohol at 4 mg/ml supported development of protein secretion as well as the crude fraction-V BSA. Blastocysts restricted to the oviduct also exhibited quantitative differences in protein secretion patterns compared to uterine blastocysts. Thus, although blastocyst development and the expression of many secreted proteins are supported outside the uterus, the full pattern of secretion characteristic of the peri-implantation embryo may be dependent on specific uterine influences. PMID- 2600561 TI - Cold shock induces actin reorganization and polyspermy in sea urchin eggs. AB - The effect of low temperature on the cortical actin system and polyspermy in sea urchin eggs was studied. Eggs cold-shocked at 3 degrees C for 1 hour formed a cortical system of polymerized actin and were polyspermic when fertilized. These effects were completely reversible following a 7-20 minute recovery period at room temperature. The present data raises the possibility that actin, or components of the egg cytoskeleton, regulate sperm entry in sea urchin eggs. PMID- 2600560 TI - Calcium requirement and increased association with bovine sperm during capacitation by heparin. AB - The requirement for external Ca+2 during capacitation of ejaculated bovine sperm with heparin and changes in sperm-associated 45Ca+2 during capacitation were investigated in vitro. Sperm capacitation was evaluated by ability to undergo an acrosome reaction (AR) upon exposure to lysophosphatidylcholine. The percentage of sperm which were capacitated during a 4 h incubation with heparin increased exponentially with increased exposure time to 2 mM Ca+2. When sperm were incubated with or without heparin in the presence of 45CaCl2, there was no difference in the amount of 45Ca+2 associated with sperm initially or at 1 h of incubation. Incubation with heparin resulted in a greater amount of sperm associated 45Ca+2 at 2, 3, and 4 h as compared to sperm incubated without heparin. The amount of 45Ca+2 associated with sperm during capacitation was unaffected by washing with 2 mM EGTA-5 mM LaCl3. Glucose (5 mM) inhibited the effects of heparin on sperm-associated 45Ca+2 and on capacitation. The inhibitory effects of glucose could be overridden by 8-bromo-cAMP. The results suggest that the requirement for external Ca+2 during capacitation with heparin may be related to an increased association of external Ca+2 with sperm. PMID- 2600562 TI - The role of refractorinesss to long daylength in the annual reproductive cycle of the female Bennett's Wallaby (Macropus rufogriseus rufogriseus). AB - The beginning of the breeding season of the female Bennett's wallaby occurs when seasonal quiescence terminates 1-2 months after the summer solstice. In this study, the role of photoperiod in terminating seasonal quiescence was examined. One week before the summer solstice, five non-lactating wallabies were transferred from natural to artificial summer solstice daylength for 5 months. The beginning of the breeding season in these animals as indicated by births, matings, and peripheral progesterone profiles was not different from that of five control animals maintained on natural photoperiod. The following year, three animals were transferred from natural to summer solstice daylength on February 25 and were held on the artificial photoperiod until September 30. Changes in plasma progesterone concentrations indicative of the beginning of the breeding season occurred on June 12-30 (range), which was significantly (P less than 0.01) advanced by 29 days when compared with six control animals. These results indicate that the decrease in daylength that occurs after the summer solstice is not required to induce the termination of seasonal quiescence at the beginning of the breeding season. Further, the beginning of the breeding season can be advanced by transferring animals to long daylength early in seasonal quiescence. Photorefractoriness to long daylengths may therefore be important in the initiation of the breeding season in this species. In further experiments, groups of six animals were transferred from natural to artificial summer solstice daylength on September 26 and December 9 and pouch young were removed 7 days after the transfer. In September, reactivation of the quiescent corpus luteum followed soon after removal of pouch young (RPY) indicating that exposure to long daylength had not induced a transition into seasonal quiescence. In December, RPY was not followed by reactivation of the quiescent corpus luteum indicating that animals were in seasonal quiescence. These results suggest that the female Bennett's wallaby may need to experience a period of shortening days after the summer solstice before exposure to long days can again initiate seasonal quiescence. PMID- 2600564 TI - The press does not like us. PMID- 2600563 TI - Delayed carpal ossification in Notophthalmus viridescens Efts: Relation to the progress of mesopodial completion in newt forelimb regenerates. AB - The persistence of cartilage in the adult newt (Notophthalmus viridescens) forelimb skeletal regenerate has recently been reported by Libbon et al. It is particularly evident in the carpal group, which remains cartilaginous for at least 9 months while all other regrown skeletal parts are either ossified or ossifying. The present investigation was undertaken to determine whether delayed ossification in the adult regenerate recapitulates a pattern evident during the development of the forelimb of the red eft (N. viridenscens' immature terrestrial phase). Right upper limbs of 20 efts were examined at low magnification to establish carpal composition and organization. Among five efts of the smallest size (26.54 plus or minus 2.20 mm snout-to-vent length), and displaying bright orange dorsal skin coloration, all carpal rudiments were cartilaginous. Eleven efts, intermediate in length (33.88 plus or minus 0.81 mm), displaying orange green coloration, all carpals had ossified. These observations demonstrate that during adult newt forelimb regeneration, the failure of the carpal elements to begin ossification in synchrony with other regrown skeletal parts duplicates a similar schedule of delayed mesopodial ossification which is evident during the development of the red eft's forelimb. PMID- 2600565 TI - Our government and its appetite for special favors. PMID- 2600566 TI - Write, write, write! PMID- 2600567 TI - Abortion and the Hippocratic Oath. PMID- 2600568 TI - One good lesson. PMID- 2600569 TI - Vitamin D deficiency in Florida, the Sunshine State. AB - Several years may be required for development of clinically evident osteomalacia in previously healthy subjects deprived of exposure to sunlight or enriched dietary sources of vitamin D. In a survey of residents of a 120 bed VA nursing home who had been patients there for two to six years, 17 were found to have x ray or laboratory findings suggestive of the presence of vitamin D deficiency. Bone biopsy in eight of these 17 patients revealed definite osteomalacia in three patients. Thus, vitamin D deficiency may develop in confined, nonvitamin D fortified patients in Florida just as in more northern climes. Daily exposure for 30 minutes to sunshine or oral administration of 2.5 mg of vitamin D2 or D3 twice yearly has been recommended to prevent deficiency of this vitamin. PMID- 2600570 TI - A protocol for outpatient management of asymptomatic human immunodeficiency infection. AB - The epidemic of HIV infection and its consequences are being increasingly encountered by primary care community physicians. The management of these patients is especially challenging. Presented here is a protocol that utilizes a flow chart for laboratory and treatment decisions and a checklist highlighting signs and symptoms to look for in regular office visits of HIV patients. Matters of legality, physicians' responsibility, insurance, lifestyle management, and prevention of opportunistic infections are discussed. The use of zidovudine (AZT) and alternative drugs is reviewed. More understanding of the special needs of HIV patients will enable the primary care physician to better serve the future needs of his community. PMID- 2600571 TI - Demythologizing the American health care process. PMID- 2600572 TI - Where the heart is. PMID- 2600573 TI - Publish or perish. PMID- 2600575 TI - Practice of plastic and reconstructive surgery in Florida. PMID- 2600574 TI - Can physicians learn anything from Frank Lorenzo? PMID- 2600576 TI - Facial skin flaps and skin grafts for skin cancers. AB - The commonly used skin flaps and skin grafts for plastic surgical reconstruction of facial wounds created by skin cancer extirpation are reviewed. PMID- 2600577 TI - New horizons in surgical rejuvenation of the aging face. AB - The development of aesthetic surgery as a major segment of plastic and reconstructive surgery is accepted among physicians. From a procedure at one time limited to the few, aesthetic surgery of the aging face has become commonplace. The patient seeking aesthetic surgery is attempting to improve self-image. The three major factors necessary for successful results are proper patient selection, a careful preoperative psychological evaluation, and expertise in carrying out the surgical procedure including management of complications. A total preoperative evaluation is essential to individualize the appropriate procedure which is correct for the particular patient. PMID- 2600578 TI - Ethical issues in professional advertising. AB - Physician advertising has received considerable attention since the courts decided in favor of the Federal Trade Commission (FTC) in its initial complaint against the American Medical Association in the 1970s. Continued investigations by the FTC into AMA opinions on advertising and publicity have promulgated a new freedom in advertising by physicians. False and deceptive advertising though is the grounds for court action as well as license revocation. This is an attempt to analyze where physician advertising is most prevalent, which physicians are doing it and why. PMID- 2600579 TI - Plastic surgery of cutaneous head and neck tumors. A different view. AB - Plastic surgery is really a multispecialty specialty. It encompasses cosmetic surgery, trauma, congenital anomalies, hand surgery, treatment of burns, genital urinary reconstruction, as well as cancer ablation and reconstruction. This paper reviews three cases of skin cancer (basal cell carcinoma, squamous cell carcinoma, and melanoma) that had a varied presentation and clinical course. PMID- 2600580 TI - New tactics in bone grafting. AB - The reconstruction of mandibular defects pose problems because of the nature of the facial skeleton. The mandibular moves continuously. In contrast, nasal and orbital bone grafts have to be immobilized. PMID- 2600581 TI - Of cabbages and kings. AB - The experience in Florida with Amendment 10 highlighted the malpractice situation for the public, physicians, and the entire United States. It was hoped that a heightened awareness might help alleviate the situation. PMID- 2600582 TI - Should we market medical practice? PMID- 2600583 TI - Medical advertising revisited. PMID- 2600584 TI - Malpractice insurance carriers in Florida 1970-1990. PMID- 2600585 TI - Chemical and biological properties of lipopolysaccharide, lipid A and degraded polysaccharide from Wolinella recta ATCC 33238. AB - Lipopolysaccharide (LPS) was isolated and purified from Wolinella recta ATCC 33238 by the phenol-water procedure and RNAase treatment. The sugar components of the LPS were rhamnose, mannose, glucose, heptose, 2-keto-3-deoxyoctonate (KDO) (3 deoxy-D-manno-octulosonate) and glucosamine. The degraded polysaccharide prepared from LPS by mild acid hydrolysis was fractionated by Sephadex G-50 gel chromatography into three fractions: (1) a high-molecular-mass fraction, eluting just behind the void volume, consisting of a long chain of rhamnose (22 mols per 3 mols of heptose residue) with attached core oligosaccharide; (2) a core oligosaccharide containing heptose, glucose and KDO, substituted with a short side chain of rhamnose; (3) a low-molecular-mass fraction containing KDO and phosphate. The main fatty acids of the lipid A were C12:0, C14:0, 3-OH-C14:0 and 3-OH-C16:0. The biological activities of the LPS were similar to those of Salmonella typhimurium LPS in activation of the clotting enzyme of Limulus amoebocytes, the Schwartzman reaction and mitogenicity for murine lymphocytes, although all the biological activities of lipid A were lower than those of intact LPS. PMID- 2600586 TI - Mechanism of staphylococcal resistance to non-oxidative antimicrobial action of neutrophils: importance of pH and ionic strength in determining the bactericidal action of cathepsin G. AB - The staphylococcalcidal action of highly purified, enzymically inactive human lysosomal cathepsin G was studied. The bactericidal action of cathepsin G was optimal at pH 7.5 and was inhibited by NaCl; concentrations greater than 0.15 M NaCl completely inhibited killing of Staphylococcus aureus. Under optimal conditions (pH, temperature and NaCl concentration) the ED50 (effective dose) of cathepsin G against S. aureus strain 8325-4 was about 3.1 micrograms ml-1. Polymeric teichoic acid may serve as a binding site for cathepsin G by promoting electrostatic interactions since a mutant lacking this surface component exhibited enhanced resistance to the lethal action of cathepsin G, compared to the teichoic-acid-positive parental strain. These results suggest that (i) the ability of cathepsin G to kill intraphagosomal staphylococci may be regulated in part by the ionic strength of the environment and the pH of the maturing phagolysosome, and (ii) that strategies which retard acidification of the developing phagolysosome would promote the staphylococcalcidal action of cathepsin G. PMID- 2600587 TI - A qualitative and quantitative study of the cellular fatty acids of 'Streptococcus milleri' with capillary gas chromatography. AB - Fatty acid analysis was done with GC and GC-MS on 21 strains of 'Streptococcus milleri', representative of the various proposed species. Although no qualitative differences were found in the fatty acid profiles, discriminant analysis of the quantitative data revealed three groups. Streptococcus anginosus and Streptococcus constellatus were indistinguishable but separated from the other two groups which comprised Streptococcus intermedius, with a wide fermentation pattern and Streptococcus intermedius with a narrow fermentation pattern. Three of the strains could be distinguished from the others by a 'fingerprint' of a particularly prominent fatty acid peak. The results support the suggestion that there is more than one species in this group of organisms and that the technique might be of value in epidemiological investigations of 'S. milleri'. PMID- 2600588 TI - The isolation and comparison of cellulase genes from two strains of Ruminococcus albus. AB - Endo-1,4-beta-glucanase genes have been cloned from two strains of Ruminococcus albus recently isolated in this laboratory. Although the strains were phenotypically similar, cross-hybridization studies between them showed significant genetic differences, with only 20% of the genome forming DNA heteroduplexes. Heteroduplexes displayed an average dissociation temperature 9 degrees C lower than that of the homoduplex. Consistent with this, restriction maps of the two endoglucanase genes showed no similarity, and hybridization work using the endoglucanase genes as probes revealed that neither gene was present in the genome of the other isolate of R. albus. Comparative enzyme characterization showed differences between the enzymes in their response to temperature, pH and substrate preference. PMID- 2600589 TI - Characterization of a cell-surface protein antigen of hydrophilic Streptococcus mutans strain GS-5. AB - Fourteen strains of Streptococcus mutans serotype c were examined for their cell surface protein antigens in terms of hydrophobicity, Mr and immunochemical specificities. Thirteen strains were hydrophobic, while strain GS-5 was markedly hydrophilic as compared to the other strains tested. Cell-surface protein antigens were then analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western immunoblotting. A protein antigen of Mr 190,000 (PAc) was found in cell extracts and culture supernatants of all the hydrophobic strains. Neither culture supernatant nor cell extract of strain GS-5 contained PAc. Strain GS-5, however, produced extracellularly a large amount of a protein of Mr 155,000 (PAGS-5) which reacted with rabbit anti-PAc serum. Immunodiffusion analysis showed that PAGS-5 lacked a part of the antigenic moieties in the PAc molecule. SDS-PAGE and radioimmunoassay showed a small amount of PAGS-5 on the cell surface of strain GS-5. These findings suggest that PAGS-5 may correspond to PAc which lacks a region participating in binding of PAc to the streptococcal cell. PMID- 2600590 TI - Delta hepatitis in Kiribati: a pacific focus. AB - From the Pacific Republic of Kiribati, 90/130 (69%) of hepatitis B-infected individuals carry antibodies to hepatitis delta virus. The prevalence of delta infection varied between geographically isolated subgroups in the population and delta antibodies were found more frequently in subjects over the age of 10. It is unlikely that delta superinfection in this population is associated with an acute hepatic illness. The prevalence of delta infection is the highest recorded from the Pacific region and thus migrants from Kiribati may have provided the source of infection in other population in this region. PMID- 2600592 TI - Increased density of HLA-DR antigen on monocytes of patients infected with the human immunodeficiency virus. AB - Monocytes and macrophages play an important role in the pathogenesis of the acquired immunodeficiency syndrome (AIDS). Dysfunction of these cells contributes to the immunocompromised state that characterizes AIDS, and they probably serve as a reservoir for the human immunodeficiency virus (HIV). HIV-infected macrophages may also be responsible for the infection of many CD4-positive lymphocytes by means of cell to cell contact during the initiation of immunological responses. The efficiency of this process would be enhanced by activation of the macrophages, since that is accompanied by increased expression of class II major histocompatibility (HLA-DR) antigen. Using a direct blood antibody marking procedure in conjunction with flow cytometry, we have analyzed the expression of HLA-DR antigen on the surfaces of monocytes present in the peripheral blood of HIV-infected patients. In contrast to the results reported by other investigators who purified the monocytes using Ficoll-Hypaque centrifugation prior to antibody marking, we found that the percentage of monocytes expressing HLA-DR antigen was identical in the patients and normal controls. However, a subpopulation of monocytes was detected in the blood of the majority of the patients that was expressing increased levels of HLA-DR antigen. It was also found that the proportion of monocytes with a high density of HLA-DR antigen on their surfaces negatively correlated with the absolute numbers of CD4 positive lymphocytes present in the peripheral blood of the patient. These findings support the postulated role of monocytes and macrophages in the HIV infection and ultimate destruction of CD4-positive lymphocytes. PMID- 2600591 TI - Serological evidence of dengue fever among refugees, Hargeysa, Somalia. AB - Epidemics of a malaria-like illness affected several thousand residents of the Dam Camp, a refugee camp near Hargeysa in Somalia, during 1985, 1986, and 1987. The disease was characterized by fever, chills, sweats, headache, back and joint pains for as long as 10 days in some patients. Blood smears from acutely ill patients were negative for malaria. Of 28 acute and 10 convalescent sera tested by the indirect fluorescent antibody (IFA) and by the hemagglutination inhibition (HI) tests, all were negative for antibody to Rift Valley fever, Crimean-Congo hemorrhagic fever, Sindbis, Chikungunya, yellow fever, and Zika viruses. However, antibody reactive to dengue 2 virus was detected by the IFA test in 39% (15/38), and 11 of 29 (38%) of the same sera were antibody positive by the HI test. Also, IgG antibody reactive to dengue 2 was demonstrated in 60% (17/28) of the same sera by the enzyme immunoassay (EIA), and 14% (4/28) were positive for IgM antibody. Of ten patients for which acute and convalescent sera were available, two developed four fold or greater rises in antibody titer evidencing infection. These data suggested that dengue virus may have been the cause of the epidemic among the Dam Camp refugees. PMID- 2600593 TI - Liver enzyme abnormalities in spinal cord injury. AB - A retrospective study of serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxalacetic transaminase (SGOT) was performed on eighteen previously healthy patients with acute spinal cord lesions C1 to L1 and no abdominal trauma. The SGPT rose in 13 of the 17 (76%). The SGOT rose in 8 of the 17 (47%). The SGPT and SGOT values for the entire group were significantly elevated over the upper limits of normal (p less than 0.01). The mean and median days of onset of elevated SGPT after trauma were 22 and 18, respectively. The mean and median days to normalization after trauma were 67 and 64. The mean and median days of onset of elevated SGOT were 26 and 19 respectively. The mean and median days to normalization were 42 and 43. The alkaline phosphatase were elevated in all but eight patients. The bilirubin was elevated in only three patients. Seventy-six percent of the quadriplegics and 60% of the paraplegics had elevated transaminases. The elevations are probably related to liver injury but the mechanism is unclear. PMID- 2600594 TI - Flexed neck posture due to cervical posttraumatic syringomyelia. AB - A flexed neck posture, especially with prolonged sitting, developed in three quadriplegic patients as a manifestation of posttraumatic syringomyelia (PTS). This posture developed at 1, 6, and 20 years after spinal cord injury. All patients complained of increasing weakness of the neck with several hours of sitting, and all required analgesics for aching neck pain. Neck weakness preceded an ascent of the level of sensory or motor deficit in two patients, and followed it in one. Current muscle testing failed to demonstrate weakness of neck extension in any patients, but electromography revealed chronic denervation and reinervation of cervical paraspinal muscles in each patient. Magnetic resonance imaging revealed a syrinx extending from the site of injury to the medulla oblongata in each case. We conclude that a flexed neck posture can represent: (1) a loss of stamina in denervated head support musculature, (2) either a precursor or successor to the conventional signs of PTS, and (3) high cervical syringomyelia. PMID- 2600595 TI - Demethylation of tertiary amines by a reconstituted cytochrome P-450 enzyme system: kinetics of oxygen consumption and hydrogen peroxide formation. AB - Initial reaction rates of oxygen consumption and hydrogen peroxide formation in a cytochrome P-450 catalyzed reaction are practically independent of the nature of tertiary amines that were used as substrates. From the kinetic studies and the substrate conversion results that the amount of water formed in a side reaction is determined by the substrate specificity. Both hydrogen peroxide and water formation lower the efficiency of the monooxygenatic activity of cytochrome P 450. PMID- 2600596 TI - UV spectroscopic studies of human erythrocyte superoxide dismutase. AB - Using UV absorption spectroscopy, first derivative spectroscopy, and UV difference spectroscopy, the active site of human superoxide dismutase is probed. First derivative spectra (dA/d lambda versus lambda) show the HESOD spectrum to be a composite of Phe and Trp absorbance. The 278 and 288 nm Trp absorbance peaks are sensitive to solvent polarity. A 5-10% decrease in these peaks accompanies copper removal from the active site indicating greater solvent access to Trp in the apoenzyme than the holoenzyme. A Trp UV difference peak at 305-310 nm documents the presence or absence of copper at the active site, and documents also the movement of a nonbridging copper-binding His (His 46 or 120) when HESOD is inhibited by azide or when the copper moiety is reduced. Trp absorbances indicate that neither cyanide nor KCl inhibition affects the Cu(II)-His bonds. Phe UV absorbance is increased by the presence of copper at the active site and increased further by the addition of cyanide or azide. Neither Trp nor Phe responds to the presence of zinc in the active site. A molecular graphics program, FRODO, shows Trp and the four Phe residues lying in an approximate ring around the active site of HESOD and thus excellently placed to report on active site perturbations. PMID- 2600597 TI - Complexes of zinc, copper, and nickel with the nonprotein amino acid L-alpha amino-beta-methylaminopropionic acid: a naturally occurring neurotoxin. AB - The non-protein amino acid L-alpha-amino-beta-methylaminopropionic acid (L-MeDAP) causes motor neuron dysfunction in macaques. The amino acid is a potent chelator of divalent metal ions such as copper and zinc. Binding constants nickel(II) for copper(II) and zinc(II) with L-MeDAP have been measured. Some copper(II) complexes of L-MeDAP have been synthesized and characterized by their electronic, infrared, and epr spectra. These results are used to comment on the possibility that metal ion complexation in the central nervous system is involved in the expression of the meurotoxicity of L-MeDAP. PMID- 2600599 TI - Noncovalent interactions in ternary complexes of spermine and copper(II) with adenosine 5'-triphosphate and tripolyphosphate. AB - Thermodynamic characteristics pertinent to the formation equilibria of two ternary systems: 1) Copper(II), 4,9-diazadodecane-1,12-diamine (spermine, Spe), and adenosine 5'-triphosphate (ATP) and 2) Copper(II), Spe, and tripolyphosphate (TPP) have been determined by means of potentiometric and calorimetric techniques, together with the parent binary complex characteristics. Ternary complexes involving ATP can give information useful in the interpretation of bioenergetic reactions and of biological interactions between nucleic acids and polyamines. As a model system, the TPP-containing ternary complexes have been studied, together with the parent binary complexes. The thermodynamic study of these systems is very important because it can give information about the structural environment of the complexes; moreover, it can help in outlining different noncovalent interactions such as coulombic forces and hydrogen bonds. PMID- 2600598 TI - Comparison of the binding of Ca2+ and Mn2+ to bovine alpha-lactalbumin and equine lysozyme. AB - The enthalpy change of the binding of Ca2+ and Mn2+ to equine lysozyme was measured at 25 degrees C and pH 7.5 by batch microcalorimetry: delta H degrees Ca2+ = -76 +/- 5 kJ mol-1, delta H degrees Mn2+ = -21 +/- 10 kJ mol-1. Binding constants, log KCa2+ = 6.5 +/- 0.2 and log KMn2+ = 4.1 +/- 0.5, were calculated from the calorimetric data. Therefore, delta S degrees Ca2+ = -131 +/- 20 JK-1 mol-1 and delta S degrees Mn2+ = 8 +/- 44 JK-1 mol-1. Removal of Ca2+ induces small but significant changes in the circular dichroism spectrum, indicating the existence of a partially unfolded apo-conformation, comparable with, but different from, the apo-conformation of bovine alpha-lactalbumin. PMID- 2600600 TI - Multinuclear NMR study of the interaction of vanadate with mononucleotides, ADP, and ATP. AB - The interaction of vanadate with 5'-mononucleotides, ADP, ATP, and various molecules containing some of their chemical moieties was studied in aqueous solution in the pH region of 5-9 using proton, 13C, 31P, and 51V nuclear magnetic resonance (NMR) spectroscopy. All the compounds studied formed noncyclic vanadate esters through interaction of monovanadate or divanadate with the hydroxyl groups of the ribose ring. Noncyclic anhydrides were also formed with the phosphate groups of ribose 5-phosphate, the mononucleotides, ADP, ATP, phosphate, pyrophosphate, and tripolyphosphate. In particular, ADP and ATP analogs resulted from AMP (AMPV and AMPV2) and from ADP (ADPV). Cyclic esters of trigonal bipyramidal geometry resulted from the interaction of vanadate with two ribose ring cis hydroxyl groups. AMP, CMP, and UMP formed two such complexes of 1:1 and 1:2 stoichiometries, similar to what has been observed for uridine and other nucleosides. However, 2'-deoxy-AMP does not yield this type of complexes. ADP and ATP also form similar cyclic ester complexes with vanadate, which does not chelate their pyrophosphate and tripolyphosphate moieties. Nevertheless, the separate pyrophosphate (PP) and tripolyphosphate (PPP) ligands form cyclic anhydrides of octahedral geometry with vanadate. However, their binding to vanadate is weaker than that of the ribose ring of nucleotides. Competition experiments between ethylene glycol and phosphate (P), pyrophosphate (PP), or tripolyphosphate (PPP) show that the relative strength of the interaction of these ligands with vanadate is PP greater than ethylene glycol greater than PPP greater than P. PMID- 2600601 TI - Effect of low doses of interleukin-2 injected perilymphatically and peritumorally in patients with advanced primary head and neck squamous cell carcinoma. AB - For 10 days, four patients with advanced squamous cell carcinoma of the head and neck received two daily injections of 100 units of natural IL-2, one around the tumor, the second near the tumor-draining lymph nodes. No side effects were observed. Histologic and ultrastructural examination of tumor and lymph nodes recovered at surgery showed that in many instances neoplastic cells were intermingled with numerous lymphocytes and eosinophils. Lymph nodes displayed hyperplasia of both cortical and paracortical areas and epithelioid venules infiltrated by lymphocytes and granulocytes. In a few cases, a decrease or disappearance of neoplastic lesions was also documented both clinically and histologically. PMID- 2600602 TI - Immunogenicity of a soluble partially purified oncofetal antigen from murine fibrosarcoma in syngeneic mice. AB - A tumor/fetal associated antigen, termed oncofetal antigen (OFA), conserved in the tumor and fetal tissue of rodents and humans, was extracted from murine fibrosarcoma cells and tumors and was fractionated on an Ultrogel AcA34 gel filtration column. A monoclonal antibody 115 specific for the OFA identified three peaks of antigenic activity in the eluted fractions, designated fractions (Fr.) I, II, and III, in the molecular weight range of greater than 160, 90, and 44 kDa, respectively. Most of the activity resided in the high molecular weight fraction, Fr. I. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and gel scanning of Fr. I showed multiple bands, one of which, constituting about 5.6% of the total protein bands in Fr. I, was the 44 kDa oncofetal antigen, apparently present in this fraction in a soluble complex form. Lectin binding studies and isoelectric focusing showed that the 44 kDa OFA is a glycoprotein, whose pI is 6.8. Spleen and peritoneal exudate cells of BALB/c mice immunized with Fr. I protected naive syngeneic mice, in adoptive transfer experiments, from developing tumors when challenged with syngeneic fibrosarcoma tumor cells, MCA-1315. Also, immune spleen cells were cytotoxic to the tumor target cells, MCA-1315, in a 51Cr release assay at several different effector to target cell ratios. This is the first description of a conserved, true, oncofetal antigen capable of inducing tumor transplantation resistance in syngeneic rodents in a semipurified form. PMID- 2600603 TI - Effects of anti-C5a antibodies on human polymorphonuclear leukocyte function: chemotaxis, chemiluminescence, and lysosomal enzyme release. AB - Previous investigation has demonstrated that in vivo complement activation can produce acute lung injury. Complement component C5a has been implicated as a key factor in this damage. In addition, C5a is thought to play a central role in mediating polymorphonuclear leukocyte (PMN) function. Studies suggest that administering antibodies to C5a might play a role in attenuating lung injury in animal models of sepsis. To evaluate further the effects of anti-C5a antibodies, we compared the effects of anti-human C5a des-Arg monoclonal (MAb) and polyclonal (PAb) antibodies on PMN functions including chemotaxis, chemiluminescence, and lysosomal release. PMN chemotaxis was assayed in Boyden chambers using 0.5% zymosan-activated serum (ZAS) as a source of C5a and 0.5% normal human serum (NHS) as a control. PMN chemiluminescence was measured by scintillation counting using ZAS as a stimulant and NHS as control. In addition, the lysosomal marker enzyme beta-D-glucuronidase was spectrophotometrically determined to assess lysosomal release. The PMN chemotactic response to ZAS was completely abolished with MAb and PAb anti-C5a antibodies (p less than 0.01). Control antibodies had no effect on ZAS-stimulated chemotaxis. The anti-C5a MAb markedly inhibited PMN chemotaxis at concentrations ranging from 20 to 0.2 microgram/ml, and was approximately 30 times more potent than the PAb. ZAS-stimulated PMN chemiluminescence was markedly decreased in response to monoclonal antibodies to C5a. In contrast, the control antibody did not inhibit ZAS-stimulated PMN chemiluminescence. Anti-C5a antibodies also significantly attenuated the release of the lysosomal enzyme beta-D-glucuronidase from ZAS-stimulated PMN. Anti-C5a antibody treatment did not cause a significant lytic effect when incubated with PMN, as demonstrated by the absence of the cytoplasmic marker lactate dehydrogenase in the supernatant. These studies suggest that in states of complement activation, MAbs and PAbs may decrease PMN functions including chemotaxis, chemiluminescence, and lysosomal enzyme release. PMID- 2600604 TI - Secretion of tumor necrosis factor during fetal and neonatal development of the mouse: ontogenic inflammation. AB - Inflammation plays an important role in homeostasis of the body. We therefore can assume that an inflammatory state occurs during ontogenesis of animals. To address this problem, we examined the ability of tumor necrosis factor (TNF), one of the inflammatory mediators, to be secreted by mouse cells during development. We cultured cells prepared from various parts of fetuses (10-19 days of gestation) and postnatal brains by collagenase digestion and assayed the secreted TNF activity by the L-929 cytotoxicity test. We found TNF activity by fetal cells without any stimulation. The spontaneous secretion of TNF was relatively high at around 13-15 days of gestation. The secretion was enhanced by lipopolysaccharide (LPS), showing that fetal cells are in an activated state for TNF secretion. These TNF activities were neutralized completely by rabbit anti-murine TNF antibody. Spontaneous and LPS-enhanced secretion by postnatal brain cells reached a peak around 7 days after birth, and thereafter declined rapidly. This time course was well correlated to the increase in the weight of brain. The producing cells were negative in macrophage marker surface antigen, and heterogeneous in relation to adherence and phagocytic activity, showing that TNF is secreted by various types of cells in the fetal body. These results suggest the presence of an inflammation-like state during ontogenesis. We consider that this "ontogenic inflammation" may be the prototype of inflammation, which can regulate homeostasis of the adult body. PMID- 2600606 TI - Advocacy for elderly autonomy: a challenge for community health nurses. AB - Community health nursing practice has always been directed by a genuine concern for other persons. Flaherty (1980) wrote that the profession now, perhaps more than ever before, requires that nurses go beyond direct care and be involved with the nature and shape of the health-care system, the practice of all team members, and "the changing roles of consumers in the maintenance of their own health" (p.8). The ethics of care in a society that no longer values old age is a challenge that must be met head on by CHNs. PMID- 2600605 TI - Distinct antitumor mechanisms of recombinant interleukin-2 on recombinant interleukin-2-activated killer-sensitive and -resistant murine tumors. AB - The antitumor mechanism of recombinant human interleukin-2 (rIL-2) was studied using two murine tumor systems. Meth 8 tumor cells were easily lysed in vitro by rIL-2-activated killer (AK) cells, which mainly consisted of Thy1.2+, Lyt2.2+, L3T4- T cells, and asialo GM1+ natural killer (NK) cells; on the other hand, X5563 tumor cells were only slightly lysed in vitro by AK cells under the same conditions. One of these two tumors was inoculated i.d. into C3H/HeN mice and then rIL-2 (5 X 10(4) J.U./mouse/day) was repeatedly injected s.c. For AK sensitive Meth 8-bearing mice, rIL-2 therapy starting 1 day after tumor inoculation was more effective for the growth than the therapy starting 7 days later and the therapeutic effect was abrogated by in vivo treatment with anti asialo-GM1 serum. In contrast, for mice bearing AK-resistant X5563 tumor cells, delayed administration starting on day 7 or later was more beneficial than earlier administration on day 1 or 4. This treatment schedule resulted in complete tumor regression in a dose-dependent manner including significant inhibition of metastases in the spleen and/or lymph nodes. These therapeutic effects of rIL-2 on X5563 were not seen in T-depleted mice with anti-mouse thymocyte serum but were found in NK-depleted mice upon treatment with anti asialo-GM1 serum. The results of these studies showed that the growth of AK sensitive Meth 8 tumor was inhibited by AK cells, while the growth and metastases of AK-resistant X5563 tumor was inhibited by tumor-specific T cells, which were generated after tumor development and activated by rIL-2 therapy, rather than AK cells. PMID- 2600607 TI - Functionally impaired elderly: their need for home nursing care. AB - An understanding of care requirements of functionally impaired elderly living in the community is especially important to community health nurses (CHNs), if they are to maximize services to elderly care recipients and their lay caregivers. This study is a report of the functional status of 53 elderly care recipients who were receiving care by informal and formal caregivers. Findings on the functional abilities of elderly in this study are compared with findings from studies of nursing home and community residing elderly. Implications for nursing practice relative to assessments and interventions for functionally impaired elderly are given. Results of the research point to the need for additional investigations to determine home-care needs of growing numbers of of frail elderly. PMID- 2600608 TI - The prevention and management of genital herpes: a community health approach. AB - The incidence of genital herpes, a sexually transmitted disease (STD) of epidemic proportions in the community, is increasing. Meeting the health needs of clients and the public concerning genital herpes is a challenge to community health nurses (CHNs). Little information is available concerning both the physical and psychosocial responses of young adults to genital herpes. This article reviews the changing epidemiology of genital herpes and the psychosocial consequences experienced by those living with the disease--emotional distress, stress associated with recurrences, sexual responses, alterations in interpersonal relationships, and coping and adaptation. The Permission-Limited Information Specific Suggestion-Intensive Therapy (P-LI-SS-IT) model, a model for intervention and referral, can be used with clients who have the disease to prevent the disabling consequences of the disease. Educating the public is necessary to prevent transmission of this silent epidemic among the population. PMID- 2600609 TI - Expanding services: the role of the community health nurse and the advanced nurse practitioner. AB - The provision of public health care is no longer within the control of the traditional public health care providers...the resources to provide public health care will not again in the forseeable future be under our control. The future of public health rests in our ability to collaborate, coordinate, and form coalitions within the communities we live and work. We must change from organizing our resources by program. In the future we will be called to organize to achieve outcomes. PMID- 2600610 TI - Mandatory testing for the AIDS antibody. AB - The appearance of Acquired Immune Deficiency Syndrome (AIDS) has brought suffering and death to those who are afflicted. At the same time, this disease has posed enormous challenges to those who care for the sufferers, to biomedical scientists, and to those responsible for public health and social policy. The issue addressed in this article is whether the implementation of mandatory testing for the AIDS antibody is an appropriate and effective strategy to use in coping with the AIDS epidemic. The goal of an AIDS prevention program is to prevent transmission of Human Immunodeficiency Virus (HIV) infections. The pro and con aspects of using mandatory AIDS antibody testing to achieve this goal are given in issue statements. The opinions of leading authorities are presented, followed by a general review of the literature. The literature is then reviewed concerning the issue as it effects the nurse as an individual, the nursing profession, and the health-care delivery system. A position is taken and specific recommendations are proposed for the profession in the areas of practice, legislation, and research. PMID- 2600611 TI - Teen sexuality in a rural community. AB - A survey of adolescents and adults was conducted to assess the causes of the teen pregnancy problem in one rural community. Thirty teens and 34 adults were interviewed and asked to respond to questions related to teen sexuality/pregnancy. The goal of the analysis was to determine differences between and similarities among adults' and teens' perceptions of teen sexuality. Results showed few significant differences between the two groups. Nonsignificance, therefore, was significant. PMID- 2600612 TI - Update: thrombolysis. PMID- 2600613 TI - Implementing a flow sheet for thrombolytic therapy. AB - Complete and accurate documentation is necessary for optimal nursing care of patients receiving thrombolytic therapy for acute myocardial infarction. A tool is necessary to facilitate smooth transition and consistent patient care in communication between the emergency department and coronary care unit. The authors have developed a simple flow sheet to be used at the bedside for a clinical research protocol involving thrombolytic therapy. PMID- 2600614 TI - The bifocal clinical nursing model: description and application to the patient receiving thrombolytic or anticoagulant therapy. AB - Carpenito's bifocal clinical nursing model enables the clinician to address the spectrum of clinical possibilities and problems associated with patients receiving thrombolytic and anticoagulant agents. Through correct application of nursing diagnoses, collaborative problems, and referrals, a global and multidisciplinary approach to patient care is achieved. PMID- 2600615 TI - Streptokinase use in children undergoing cardiac catheterization. AB - The development of cardiac catheterization procedures in the pediatric population has evolved from diagnostic in nature to present day advanced technology and interventions. A complication of vessel occlusion secondary to large catheters, length of procedures, and patient size requires immediate intervention. The advent of thrombolytic agents has provided a highly effective mode of treatment in restoring circulation. The use of streptokinase, its efficacy, side effects, and nursing management are discussed. PMID- 2600616 TI - Competency-based education in thrombolytic therapy: a modular approach. AB - Continuing education of nurses in therapeutic advancements poses a challenge to nurse educators and managers. The competency-based educational method is a way to prepare nurses and subsequently evaluate performance based on derived standards. In this article a competency-based education approach to the use of thrombolytic therapy in acute myocardial infarction is examined. PMID- 2600617 TI - Computerizing the intensive care unit: current status and future directions. AB - Computers are serving intensive care patients by simplifying and improving the accuracy of data acquisition, facilitating communications, storing and organizing patient records, and providing expert suggestions. The future will bring many changes in the way nurses practice in intensive care. The computer should be considered an evolutionary tool to help effect these changes. PMID- 2600618 TI - Current management concepts for the patient with lymphedema. AB - The patient who is hospitalized for medical management of lymphedema presents complex issues for the nurse. Developing a care plan that will direct nursing interventions during the acute phase demands an understanding of the chronicity of the problem. The patient will require considerable teaching and support before discharge. This article provides the reader with concepts applicable to this debilitating condition. PMID- 2600619 TI - Strategies for muscle activation during isometric torque generation at the human elbow. AB - 1. We studied the patterns of electromyographic (EMG) activity in elbow muscles of 14 normal human subjects. The activity of five muscles that act in flexion extension and forearm supination-pronation was simultaneously recorded during isometric voluntary torque generation, in which torques generated in a plane orthogonal to the long axis of the forearm were voluntarily coupled with torques generated about the long axis of the forearm (i.e., supination-pronation). 2. When forearm supination torques were superimposed on a background of elbow flexion torque, biceps brachii activity increased substantially, as expected; however, brachioradialis and brachialis EMG levels decreased modestly, a less predictable outcome. The pronator teres was also active during pure flexion and flexion coupled with mild supination (even though no pronation torque was required). This was presumably to offset inappropriate torque contributions of other muscles, such as the biceps brachii. 3. When forearm supination torque was superimposed on elbow extension torque, again the biceps brachii was strongly active. The pronator teres also became mildly active during extension with added pronation torque. These changes occurred despite the fact that both the pronator and biceps muscles induce elbow flexion. 4. In these same elbow extension tasks, triceps brachii activity was also modulated with both pronation or supination loads. It was most active during either supination or pronation loads, again despite the fact that it has no mechanical role in producing forearm supination pronation torque. 5. Recordings of EMG activity during changes in forearm supination-pronation angle demonstrated that activation of the biceps brachii followed classic length-tension predictions, in that less EMG activity was required to achieve a given supination torque when the forearm was pronated (where biceps brachii is relatively longer). On the other hand, EMG activity of the pronator teres did not decrease when the pronator was lengthened. Triceps EMG was also more active when the forearm was supinated, despite its having no direct functional role in this movement. 6. Plots relating EMG activity in biceps brachii, brachialis, and brachioradialis at three different forearm positions revealed that there was a consistent positive near-linear relationship between brachialis and brachioradialis and that biceps brachii is often most active when brachioradialis and brachialis are least active. 7. We argue that, for the human elbow joint at least, fixed muscle synergies are rather uncommon and that relationships between muscle activities are situation dependent.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600621 TI - Intracellular analysis of trigeminal motoneuron rhythmical activity during stimulation of pontomedullary reticular formation in anesthetized guinea pig. AB - 1. The effects of repetitive stimulation of the nucleus pontis caudalis and nucleus gigantocellularis (PnC-Gi) of the reticular formation on jaw opener and closer motoneurons were examined. The PnC-Gi was stimulated at 75 Hz at current intensities less than 90 microA. 2. Rhythmically occurring, long-duration, depolarizing membrane potentials in jaw opener motoneurons [excitatory masticatory drive potential (E-MDP)] and long-duration hyperpolarizing membrane potentials [inhibitory masticatory drive potentials (I-MDP)] in jaw closer motoneurons were evoked by 40-Hz repetitive masticatory cortex stimulation. These potentials were completely suppressed by PnC-Gi stimulation. PnC-Gi stimulation also suppressed the short-duration, stimulus-locked depolarizations [excitatory postsynaptic potentials (EPSPs)] in jaw opener motoneurons and short-duration, stimulus-locked hyperpolarizations [inhibitory postsynaptic potentials (IPSPs)] in jaw closer motoneurons, evoked by the same repetitive cortical stimulation. 3. Short pulse train (3 pulses; 500 Hz) stimulation of the masticatory area of the cortex in the absence of rhythmical jaw movements activated the short-latency paucisynaptic corticotrigeminal pathways and evoked short-duration EPSPs and IPSPs in jaw opener and closer motoneurons, respectively. The same PnC-Gi stimulation that completely suppressed rhythmical MDPs, and stimulus-locked PSPs evoked by repetitive stimulation to the masticatory area of the cortex, produced an average reduction in PSP amplitude of 22 and 17% in jaw closer and opener motoneurons, respectively. 4. PnC-Gi stimulation produced minimal effects on the amplitude of the antidromic digastric field potential or on the intracellularly recorded antidromic digastric action potential. Moreover, PnC-Gi stimulation had little effect on jaw opener or jaw closer motoneuron membrane resting potentials in the absence of rhythmical jaw movements (RJMs). PnC-Gi stimulation produced variable effects on conductance pulses elicited in jaw opener and closer motoneurons in the absence of RJMs. 5. These results indicate that the powerful suppression of cortically evoked MDPs in opener and closer motoneurons during PnC Gi stimulation is most likely not a result of postsynaptic inhibition of trigeminal motoneurons. It is proposed that this suppression is a result of suppression of activity in neurons responsible for masticatory rhythm generation. PMID- 2600620 TI - Repetitive firing properties of neurons in the ventral region of nucleus tractus solitarius. In vitro studies in adult and neonatal rat. AB - 1. A brain stem slice preparation and intracellular techniques were used to examine the cellular properties of neurons within the ventral and ventrolateral region of the nucleus tractus solitarius (v-NTS) in adult and neonatal (3-12 days old) rats. These neurons are believed to be involved in the control of respiratory function. 2. On the basis of their active and passive electrophysiologic properties, cells in the v-NTS of adult rats were categorized into type A and type B neurons. Type A neurons fired spontaneously with rates ranging from 0.5 to 5 spikes/s at resting potential (-59.0 +/- 6 mV, mean +/- SD). When depolarized, type A cells responded with an initial high rate of firing, which rapidly declined to a steady state level. Spike-frequency adaptation (SFA) index (defined as steady state firing divided by peak activity x 100) was 40%, with a time constant for adaptation of 100-280 ms. When depolarized from membrane potentials more negative than resting, these neurons exhibited a silent period (up to 900 ms) before any spiking was observed (delayed excitation). The delay depended on the duration and magnitude of the hyperpolarizing prepulse that preceded depolarization. The action potentials of type A cells had a shoulder on the repolarization phase, measured 2-3 ms at one half height, and increased in duration during repetitive firing. 3. At resting potential, type B neurons fired three to five times faster than type A. Although both type A and type B neurons showed spike-frequency adaptation, type B neurons adapted at a much faster rate than type A. The time constant for adaptation was 2 14 ms in type B cells. These cells displayed no delayed excitation on depolarization from membrane potentials more negative than rest. Some type B cells exhibited postinhibitory rebound (PIR) and depolarizing afterpotentials (DAPs). Both types A and B v-NTS neurons had comparable input resistance and showed inward rectification. 4. Neonatal v-NTS cells, in contrast to adult cells, belonged to a single population of neurons. Their resting membrane potential was 58 +/- 6.3 mV (mean +/- SD). The majority of these cells (30/34) were active (5 10 spikes/s) at rest. When depolarized, they showed an immediate increase in firing rate, which gradually slowed down to reach a steady state. Spike-frequency adaptation index was 59%, with a time constant for adaptation of 300-750 ms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600622 TI - Synaptic connections between motor neurons and interneurons in the fourth thoracic ganglion of the crayfish, Procambarus clarkii. AB - 1. A new preparation of the thoracic nervous system of the crayfish, Procambarus clarkii, has been developed, in which it is possible to work with identified members of motor neuronal pools. 2. In such a preparation, it is possible to dissect all specific proximal motor nerves (protractor, retractor, anterior elevator, posterior elevator, and depressor). Motor neurons innervating the four proximal muscles of the fourth walking leg have been identified both physiologically and anatomically by staining the recorded motor neuron with Lucifer yellow through the microelectrode. 3. By the use of cobalt chloride, we have mapped the distribution of somata of all motor neurons within the fourth thoracic ganglion that innervate the different groups of muscles controlling the movement of the fourth walking leg. 4. Most motor neurons innervating the same muscle seem to be electrically coupled, except some depressor motor neurons. 5. Motor neurons innervating antagonist muscles are linked by inhibitory connections. These connections are reciprocal for protractor and retractor motor neurons but usually not reciprocal between elevator and depressor motor neurons. 6. Walking interneurons were identified as neurons without axons in any motor nerve, which modified the motor neuronal activity. Some of them have been injected with Lucifer yellow. 7. Some interneurons make synaptic connections only with antagonist motor neurons that control the movement of one joint. Probably their functional role is to reinforce or to limit the antagonism between each pair of antagonist motor neurons. 8. Other interneurons make synaptic connections with motor neurons innervating muscles controlling different leg joints. These interneurons may play a role in generating the motor patterns that underlie forward and backward walking. PMID- 2600623 TI - Descending pathways to the cutaneous trunci muscle motoneuronal cell group in the cat. AB - 1. The cutaneus trunci muscle (CTM) is a thin broad sheet of skeletal muscle just beneath the skin. It does not contain muscle spindles and receives its afferents from the overlying skin. Contraction of the muscle can easily be triggered by pinching the skin or, in the cat, by gentle displacement of the fur (CTM reflex). The afferent information of this reflex is conveyed via the cutaneous nerves, which are segmentally organized. In the cat, the CTM motoneurons are located in a circumscribed cell group in the ventrolateral part of the ventral horn of the C8 and T1 spinal segments. The CTM motor nucleus corresponds with "nucleus X" of Giovanelli Barilari and Kuypers and with "ventral motor nucleus" of Matsushita and Ueyama. 2. Relatively long ascending propriospinal pathways, originating in the thoracolumbar cord, exist between the cutaneous afferents and the CTM motor nucleus. Such pathways have been described physiologically, as well as anatomically. Our results, based on anterograde autoradiographic experiments with [3H]leucine injections in the C1, C2, C6, and C8 segments, suggest that propriospinal pathways to the CTM motor nucleus originating in the cervical cord do not exist, although these propriospinal projections are very strong to all other motoneuronal cell groups surrounding the CTM motor nucleus. 3. The present results also demonstrate specific supraspinal projections to the CTM motor nucleus originating in 1) the contralateral nucleus retroambiguous (NRA) and 2) the ipsilateral dorsolateral pontine tegmentum. These projections suggest that the CTM motor nucleus is not only involved in spinal reflexes, but also in other functions such as abdominal straining.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600624 TI - Spatial summation of heat-induced pain: influence of stimulus area and spatial separation of stimuli on perceived pain sensation intensity and unpleasantness. AB - 1. Psychophysical experiments were initiated to determine the possible influence of increasing stimulus size on perceived pain intensity. Six trained human subjects (5 male, 1 female) made visual analogue scale (VAS) ratings for pain sensation intensity and unpleasantness in response to nociceptive thermal stimuli. Test stimuli consisted of 5-s duration heat pulses (45-50 degrees C in 1 degrees increments) delivered by one, two, or three contact thermal probes (1 cm2 each) applied to the medial aspect of the anterior forearm. 2. The area of skin receiving noxious thermal stimuli was changed by randomly varying the number of thermodes activated. The effects of varying the distance between the thermal probes also were evaluated. In the first series of experiments, thermal-probe separation was kept close to 0; in subsequent experimental series, the thermodes were separated by either 5 or 10 cm. 3. In each experimental series, considerable spatial summation occurred in both pain-sensation intensity and unpleasantness dimensions of pain. This summation occurred throughout the nociceptive thermal range of 45-50 degrees C and was larger at suprathreshold temperatures (greater than or equal to 47 degrees C) than those near threshold (less than or equal to 46 degrees C). Unlike spatial summation of perceived warmth, that of pain was not characterized by systematic changes in power-function exponents but as approximately upward parallel displacements in double-logarithmic coordinates. 4. Thermal-probe separation over a range of 0-10 cm had no effects on spatial summation of pain-sensation intensity or pain unpleasantness. In contrast, increasing thermal-probe separation increased the subjects' ability to discriminate differences in stimulus size and their ability to detect correctly the number of thermal probes activated. 5. Because affective VAS ratings of unpleasantness were linearly related to, but distinctly and systematically less than, VAS ratings of pain-sensation intensity, it was clear that subjects responded quite differently to these two pain dimensions. Affective judgements were not additionally influenced by thermal probe separation and hence by the ability to perceive stimulus size or number of thermal probes activated. 6. The results indicate that powerful spatial-summation mechanisms exist for heat induced pain. Spatial summation of pain is likely to be subserved both by local integration mechanisms at the level of single spinothalamic-tract neurons and by recruitment of central nociceptive neurons, because spatial summation of pain occurred to approximately equal extents under conditions of thermode separations over a distance of at least 20 cm. PMID- 2600625 TI - Inward rectification in rat nucleus accumbens neurons. AB - 1. Intracellular recordings were made from neurons in slices cut from the rat nucleus accumbens septi. Membrane currents were measured with a single-electrode voltage-clamp amplifier in the potential range -50 to -140 mV. 2. In control conditions (2.5 mM potassium), the resting membrane potential of the neurons was 83.4 +/- 1.1 (SE) mV (n = 157). Steady state membrane conductance was voltage dependent, being 34.8 +/- 1.7 nS (n = 25) at -100 mV and 8.0 +/- 0.7 nS (n = 25) at -60 mV. 3. Barium (1 microM) markedly reduced the inward rectification and caused a small inward current (40.6 +/- 8.7 pA, n = 8) at the resting potential. These effects became larger with higher barium concentrations, and, in 100 microM barium, the current-voltage relation was straight. 4. The block of the inward current by barium (at -130 mV) occurred with an exponential time course; the time constant was approximately 1 s at 1 microM barium and less than 90 ms with 100 microM. Strontium had effects similar to those of barium, but 1000-fold higher concentrations were required. Cesium chloride (2 mM) and rubidium chloride (2 mM) also blocked the inward rectification; their action reached steady state within 50 ms. 5. It is concluded that the nucleus accumbens neurons have a potassium conductance with many features of a typical inward rectifier and that this contributes to the potassium conductance at the resting potential. PMID- 2600626 TI - Visual activity in area V2 during reversible inactivation of area 17 in the macaque monkey. AB - 1. The presence of a direct lateral geniculate nucleus (LGN) input to area V2 raises the possibility that some neurons in this area remain active when area 17 is inactivated. It is also known that many neurons in area MT are visually responsive in the absence of input from area 17. Because MT sends a strong projection to V2, it appears likely that visual activity could be transferred to V2 through this feedback connection when the V1 afferents are disabled. For these reasons, we decided to reexamine the residual visual activity of neurons in V2 during inactivation of area 17. A circular region 16 mm in diameter on the opercular part of area 17 was cooled by a thermoelectric Peltier device, and single- and multiunit activity was recorded in the retinotopically corresponding region of area V2. 2. Because of the proximity of areas V1 and V2, it was necessary to make sure that neurons in V2 could not be directly blocked by cooling applied to V1. Temperature gradients within cortex were measured with a specially designed thermocouple at different heat flows imposed by the Peltier device. Gradients ranged between 2.3 and 5.5 degrees C/mm. Knowing the temperature gradients and the temperature of the cooling plate, it was possible to deduce the temperature at a given depth within cortex. With this method we measured the blocking temperatures of neurons in area 17, i.e., the temperature at which neurons completely ceased to respond to optimal visual stimulation. Blocking temperatures ranged between 4 and 18 degrees C, values that are substantially lower than those reported in previous papers. Knowing the blocking temperatures, it was possible to determine the cooling-plate temperature necessary to entirely block the region of V1 under the cooling plate. Using the temperature gradients, we then calculated the depth of recording for which V2 neurons could not be directly blocked by the cold. For this reason, all our recordings were made in or near the fundus of the lunate sulcus. 3. During cryoblocking of V1, we recorded 154 sites in penetrations normal to area V2. All these sites had receptive fields included within the visual-field region coded in the cooled zone. In addition, we recorded 55 sites in tangential penetrations aimed at traveling in V2 for long distances. Among these 209 sites, only 3 could be considered as unambiguously active when V1 was blocked. Two of these sites were located at or close to the V2-V3 border.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600627 TI - Classification of unit types in the anteroventral cochlear nucleus: PST histograms and regularity analysis. AB - 1. The responses of neurons in the anteroventral cochlear nucleus (AVCN) of barbiturate-anesthetized cats are characterized with regard to features of their responses to short tone bursts (STBs; 25 ms). A "decision tree" is presented to partition AVCN units on the basis of post-stimulus time histogram (PSTH) shape, first spike latency, and discharge rate and regularity calculated as functions of time during responses to STBs. The major classes of AVCN units (primary-like, primary-like-with-notch, chopper, and onset) have been described previously; in this paper, special attention is given to clarifying and systematizing boundaries between classes. Certain types of "unusual" units that may be confused with units in one of the major classes are also examined. 2. When STBs are presented synchronously (constant phase at onset), PSTHs of responses to very-low-frequency (less than 1.0 kHz) tones are difficult if not impossible to resolve into the classes listed above because all unit types phase-lock to low-frequency tones. However, when STBs are presented asynchronously, the responses of units with low best frequencies can be categorized on the basis of PSTH shape and first spike latency. 3. Primary-like, primary-like-with-notch, and onset units are distinguished primarily on the basis of PSTH shape. These three unit types have comparable minimum first spke latencies and synchronization to tones. One type of "unusual" response poses a particular hazard with respect to the generation of uncontaminated primary-like populations. Such "unusual" units have PSTHs that appear primary-like; these units are, however, distinguished by their unusually long first spike latencies. Unlike primary-like units, these "unusual" units show extremely poor synchronization to tones. 4. Chopper units are defined as having an initial response that is highly regular, resulting in the characteristic multimodal PSTH. "Unusual" units with multimodal PSTHs but whose initial responses are not highly regular (measured by the reproducibility of the initial firing pattern in response to multiple repetitions of a STB) are eliminated from the chopper populations. 5. In barbiturate-anesthetized cats, at least three patterns of chopper response can be distinguished on the basis of temporal patterns of rate and regularity adaptation. "Sustained" choppers show no adaptation of instantaneous rate (measured by the inverse of the mean interspike interval), and their discharge remains highly regular throughout the response. "Transiently adapting" choppers undergo a very rapid (less than 10 ms) decrease in instantaneous rate accompanied by a sharp increase in discharge irregularity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600628 TI - Morphological and functional aspects of two different types of hair cells in the goldfish sacculus. AB - 1. With the use of whole-cell mode of the patch-clamp method, we examined the electrical responses of hair cells enzymatically isolated from the goldfish sacculus. 2. Hair cells from the rostral saccule had a short cell body and were ovoidal or eggplantlike in shape, whereas hair cells from the caudal saccule had a variable shape. Many had a longer cell body and were cylindrical or gourd-like in shape, but some short hair cells were also present in the caudal saccule. 3. The short hair cells had a resting potential of about -75 mV. In current-clamp experiments, these hair cells elicited damped oscillatory-potential changes of a relatively small amplitude in response to a depolarizing current. A current in the opposite direction produced a slow hyperpolarization, much larger in amplitude. 4. Resonant frequency of the short, or the oscillatory, type of hair cells ranged from 40 to 200 Hz or higher. However, resonance was generally of a poor quality as compared with that noted for hair cells in the turtle cochlea or frog sacculus. 5. The long hair cells had a resting potential of -90 to -100 mV. In current-clamp experiments, these hair cells elicited an all-or-none spike approximately 50 mV in amplitude in response to a depolarizing current. The spike was usually followed by a plateau, which was maintained for the duration of the depolarizing pulse. In some hair cells, damped slow oscillatory waves were evoked at a rate of 5-15 Hz. On the other hand, a hyperpolarizing current produced potential changes much smaller in amplitude. 6. Voltage-clamp experiments showed that Ca2+-activated K+ channel and A-current, especially its high-threshold subclass, were involved in the generation of outward rectification in the oscillatory-type hair cells. On the other hand, Na+, in addition to Ca2+, was involved in the generation of spike in the spike-type hair cells. Spike potentials were elicited even in the presence of tetrodotoxin (TTX), but the rate of rise was slower as compared with the intact spikes. 7. The spike-type hair cells had an inwardly rectifying K+ channel similar to that noted in the tunicate egg and chick vestibular hair cell. However, the oscillatory-type hair cells had an inwardly rectifying channel similar to the hyperpolarization-activated current, Ih, of the rod inner segment, or sinoatrial nodal cell, or lacked the inwardly rectifying channel. Differences in the resting membrane potential between the oscillatory- and spike-type hair cells are probably related to differences in the inwardly rectifying channels. 8. Effects of sound stimulation were simulated by injecting a half-wave rectified sinusoidal current of various frequencies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600629 TI - Task and fatigue effects on low-threshold motor units in human hand muscle. AB - 1. The activity of single motor units was recorded in the first dorsal interosseus muscle of human subjects while they performed an isometric ramp-and hold maneuver. Motor-unit activity was characterized before and after fatigue by the use of a branched bipolar electrode that was positioned subcutaneously over the test muscle. Activity was characterized in terms of the forces of recruitment and derecruitment and the discharge pattern. The purpose was to determine, before and after fatigue, whether motor-unit activity was affected by the direction in which the force was exerted. 2. Regardless of the task during prefatigue trials, interimpulse intervals were 1) more variable during increases or decreases in force than when force was held constant at the target value (4-6% above the recruitment force), and 2) more clustered around an arbitrary central value than would be expected with a normal (Gaussian) distribution. Both effects were seen during the flexion and abduction tasks. The behavior of low-threshold motor units in first dorsal interosseus is thus largely unaffected by the direction of the force exerted by the index finger. The absence of a task (i.e., a direction of force) effect suggests that the resultant force vector about the metacarpophalangeal joint of the index finger is not coded in terms of discrete populations of motor units, but, rather, it is based on the net muscle activity about the joint. 3. Motor-unit behavior during and after fatigue showed that the relatively homogeneous behavior seen before fatigue could be severely disrupted. The fatiguing protocol involved the continuous repetition, to the endurance limit, of a 15-s ramp-and-hold maneuver in which the abduction target force was 50% of maximum and was held for 10-s epochs (ramps up and down were approximately 2 s each). Motor-unit threshold was assessed by the forces of recruitment and derecruitment associated with each cycle of the fatigue test. Changes in recruitment force during the protocol were either minimal or, when present, not systematic. In contrast, the derecruitment force of all units exhibited a marked and progressive increase over the course of the test. 4. After the fatigue test, when the initial threshold tasks were repeated, the behavior of most motor units changed. These changes included the derecruitment of previously active motor units, the recruitment of additional motor units, and an increased discharge variability of units that remained recruited. The variation in recruitment order seemed to be much greater than that reported previously for nonfatiguing conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600630 TI - Does an extraocular proprioceptive signal reach the superior colliculus? AB - 1. The primary functions of the superior colliculus (SC) are thought to include both the spatial localization of sensory stimuli and the initiation of an orienting response. It has been hypothesized that, in cat, both of these SC functions may be influenced by feedback from the extraocular muscles. The present investigation was initiated to determine which SC cells receive this extraocular muscle feedback and how this feedback influences the discharge properties of SC cells and their ability to integrate input from other sensory modalities. These questions were addressed in cats prepared with various anesthetic agents. 2. During the course of these experiments it became apparent that responses of SC cells to extraocular muscle stimulation could be elicited only under very specific conditions, and these observations questioned the existence of functional extraocular inputs to SC cells. 3. Rotating the eye or stretching the extraocular muscles was never found to be effective in activating SC cells unless the drug chloralose was used in the experimental preparation. In these chloralose anesthetized animals, responses to eye rotation or muscle stretch were long and variable in latency, the discharge did not reflect the metrics of the stimulus, and the velocity and amplitude thresholds of these cells usually exceeded the cat's oculomotor range. Responses usually consisted of one to three impulses and, in appropriate conditions, could be inhibited by responses to visual or auditory stimuli. 4. The origin of this SC response to eye rotation/extraocular-muscle stretch could not be localized to the extraocular muscles. Responses to passive stretch of extraocular muscles were not eliminated by anesthetizing the muscles with injections of lidocaine. Active contraction of the extraocular muscles induced by electrical stimulation of the oculomotor nerve was never observed to evoke SC responses. Furthermore, transection of the muscle nerves, which isolated the extraocular-muscle receptors from the CNS, did not affect the response initiated by stretching the extraocular muscles. However, in the absence of intact muscle nerves, pulling the periorbital tissue elicited responses very much like those produced by stretching the muscles in the intact preparation, suggesting the periorbita as the source of responses in intact preparations as well. 5. These data are not consistent with the hypothesis that feedback from extraocular-muscle receptors influences the activity of SC cells. PMID- 2600631 TI - Glycine-gated chloride current in acutely isolated rat hypothalamic neurons. AB - 1. Electrical and pharmacologic properties of glycine-induced currents were investigated in single hypothalamic neurons acutely isolated from young and adult rats by the use of a "concentration-clamp" technique, which allows both internal perfusion and rapid application of an external solution under single-electrode voltage-clamp. 2. The glycine-induced current reversed at the Cl- equilibrium potential (ECl), and a 10-fold decrease of extracellular Cl- with a large impermeable anion resulted in a 53 mV shift of the glycine reversal potential (EGly). 3. Glycine-induced Cl- currents (ICl) increased sigmoidally in a concentration-dependent manner with a Kd of 9 X 10(-5) M at a Hill coefficient of 1.8. Current inactivation occurred completely at all concentrations within 10 s. EGly remained unchanged during continuous application of glycine, suggesting that the inactivation process is because of desensitization. 4. The glycine-induced conductance exhibited a striking voltage dependency at membrane potentials more negative than -50 mV and reached a steady state value when hyperpolarized beyond 110 mV. 5. Both the activation and inactivation phases of glycine-induced ICl are described by double exponential (fast and slow components) functions with the concentrations used. All four time constants decreased with increasing glycine concentration. 6. The slow time constant of the current decay induced by glycine increased with depolarization and decreased with hyperpolarization, indicating that the rate of desensitization is considerably voltage dependent. The fast decay showed little voltage dependency. 7. Recovery of the glycine response after complete desensitization consisted of two components. 8. The blockade of the glycine response by strychnine and picrotoxin was noncompetitive. PMID- 2600632 TI - Simulation of motion on the skin. I. Receptive fields and temporal frequency coding by cutaneous mechanoreceptors of OPTACON pulses delivered to the hand. AB - 1. Tactile discrimination of form requires motion of the hand across the object scanned. To dissociate lateral distortion of the skin from neuronal processing mechanisms involving multiple receptor classes and parallel central networks, we have simulated motion of bar patterns across the fingers and palm by the use of a computer-controlled grid of sequentially activated probes (OPTACON stimulator). Horizontal bar patterns have been swept across the hand at speeds of 30-120 mm/s to quantitatively characterize responses of cutaneous mechanoreceptive afferents recorded in the median and ulnar nerves. 2. Mechanoreceptors with phasic responses to pressure are activated by spatial patterns on the OPTACON, whereas those with tonic pressure responses are not; moving-bar patterns strongly excite both Meissner's afferents [rapidly adapting (RA) mechanoreceptors] and Pacinian corpuscles (PCs) but fail to excite slowly adapting (SA) afferents. OPTACON-type stimulators thus allow selective activation of phasic mechanoreceptor channels with spatially complex stimuli. 3. RA afferents respond in an all-or-none fashion to activation of two to five adjacent rows spanning 1-5 mm on the finger, with nearly identical latencies on all trials; response profiles are remarkable for their regularity and reproducibility. PCs have larger fields (4-13 rows) and stronger but more irregular responses than RAs. 4. Uniform sensitivity throughout the receptive field is a consistent feature of RA responses. Individual mechanoreceptor terminals appear to have equal access to the spike initiation zone and provide the same amplitude input as the fiber discharges 1 spike/pulse at each field location in 75% of the RAs tested. Uniform sensitivity allows each afferent to transmit a repetitive signal of the parameter of interest such as object speed, contour, or texture. 5. One-quarter of RAs fire two spikes to probe indentation and retraction at the field center. Such graded responses are usually observed in only one direction of motion, reflecting a preferred sequence of receptor activation rather than a specific location on the skin. PCs fire bursts of two to four spikes throughout most of their receptive fields; sensitivity is broadly distributed rather than peaked. Thus phasic mechanoreceptors fail to provide a precise signal of stimulus location; localization at the level of individual papillary ridges appears to be signaled by a population mechanism involving unique combinations of RA, SA, and PC afferents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600633 TI - Simulation of motion on the skin. II. Cutaneous mechanoreceptor coding of the width and texture of bar patterns displaced across the OPTACON. AB - 1. These experiments assay the functional significance of receptive-field architecture for information processing. Rapidly adapting (RA) afferents have been previously shown to converge information from clusters of 14-25 Meissner's corpuscles, whereas afferents innervating Pacinian corpuscles (PCs) have only a single, large receptor terminal. We tested two opposing hypotheses of functional architecture: 1) summation models, in which an afferent integrates signals from all of its terminals, showing monotonic increases in activity as a function of contact area, and 2) winner-take-all models, in which the most strongly activated receptor in the cluster dominates axonal output by cancellation of signals from other branches. 2. Bar and stripe patterns have been swept across the finger or palm of the monkey's hand at speeds of 30-120 mm/s with the use of a computer controlled grid of sequentially activated miniature probes (OPTACON stimulator). The dense packing of OPTACON probes permits placement of up to five groups of stimulators within an individual receptive field, allowing us to activate one or more clusters of Meissner's corpuscles simultaneously and to stimulate the bulbar corpuscle of PC afferents at different orientations through the skin. Integration of information from moving bar patterns has been tested with two protocols. In the variable width protocol, the total number of activated rows in the pattern is varied from one to five, with a constant spacing of 1.2 mm between pulsed rows. In the variable density protocol, the length of skin stimulated is held constant at 5 mm and the spacing of stimuli varied. 3. RA afferents show no evidence of summation of inputs within their receptive fields. Motion of wide bars across the field increases the duration of firing but not the total spikes evoked by each pulse. Responses to the leading edge of wide bars were found to be identical to those evoked by a single-row bar. Simultaneous activation of two to five rows evokes the same or fewer spikes per pulse than the most effective individual row tested alone. When broad-bar patterns are centered over the field, contacting the maximum number of receptors, RAs follow activity in the dominant branch or terminus, suppressing additional inputs. Lack of summation is observed at all pulse frequencies tested (25-100 Hz). 4. Moving bar patterns evoke responses as long as at least one row stimulates the receptive field; broader patterns evoke longer spike trains whose total number of impulses is proportional to bar width.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600635 TI - Nature and scope of changes in dental hygiene education standards. PMID- 2600634 TI - Ammonium decreases excitatory synaptic transmission in cat spinal cord in vivo. AB - 1. Glutamine is thought to be a precursor of the pool of glutamate that is used as synaptic transmitter. NH4+ inhibits glutaminase, the enzyme presumed to cleave glutamine into glutamate in synaptic terminals. Therefore a decrease by NH4+ of excitatory synaptic transmission in hippocampus was suggested to be due to the inability to utilize glutamine as a precursor for glutamate and subsequent transmitter depletion. This study reexamines the effects of NH4+ on excitatory synaptic transmission. 2. The effects of NH4+ on excitatory synaptic transmission from low-threshold afferent fibers, presumably Ia-afferent fibers, to motoneurons was investigated in the spinal cord of anesthetized cats in vivo. 3. Action potentials of low-threshold afferent fibers were recorded at the entry of the dorsal roots into the spinal cord. An extracellular electrode within a motoneuron nucleus recorded the action potential of low-threshold afferent fibers and the extracellular monosynaptic excitatory postsynaptic potential, i.e., the focal synaptic potential (FSP). This extracellular electrode also recorded the antidromic field potential (AFP) in response to ventral root stimulation. Electrodes on the ventral roots recorded the monosynaptic reflex (MSR) and the monosynaptic excitatory postsynaptic potential in motoneurons electrotonically conducted into the ventral roots (VR-EPSP). 4. Intravenous infusion of ammonium acetate (AA) reversibly decreased MSR, VR-EPSP, and FSP, i.e., decreased excitatory synaptic transmission. 5. The decrease of VR-EPSP and FSP was accompanied initially by a decrease of conduction and, eventually, a conduction block in presynaptic terminals of low-threshold afferent fibers. 6. The decreases of VR-EPSP and FSP were also accompanied by the transient appearance of a reflex discharge, triggered by VR-EPSPs of decreased amplitude, and changes of the AFP indicating increased invasion of motoneuron somata by antidromic action potentials. 7. It is suggested that NH4+ depolarizes intraspinal Ia-afferent fibers and motoneurons. This depolarization initially decreases and then blocks conduction of action potentials into the presynaptic terminals of Ia-afferent fibers. The conduction block prevents the release of excitatory transmitter and decreases excitatory synaptic transmission. 8. The suggested depolarizing action of NH4+ may be due to K+-like ionic properties of NH4+ and/or an inhibition of K+ uptake into astrocytes. 9. The conduction block in presynaptic terminals of low threshold afferent fibers can fully explain the decrease of excitatory synaptic transmission by NH4+. Because of the conduction block in presynaptic terminals, this study does not permit a conclusion as to an inhibition by NH4+ fo the utilization of glutamine as a precursor for glutamate used as synaptic transmitter. PMID- 2600637 TI - When patients refuse treatment. PMID- 2600636 TI - Articulation in dental hygiene education from the student's perspective. AB - Articulation deals with the transfer of associate degree and certificate dental hygiene students to four-year colleges or universities to complete baccalaureate degrees in the most efficient manner possible. Since a buyer's market exists in higher education at the present time, informed student consumers can select degree completion programs that will best meet their specific long-term career goals. The advantages of securing the bachelor's degree, the degree completion options available, and the factors that affect the articulation process are discussed. Recommendations are offered on how to acquire information about degree completion programs. Questions that students should ask before making a final choice of a four-year institution are also presented. Advance planning by students is a key to future mobility and career adaptability in dental hygiene. To this end, high school and college counselors and faculty members in all dental hygiene programs are instrumental in the articulation process. PMID- 2600638 TI - Renal failure. Complications and oral findings. AB - Due to the increase in the number of patients with renal disease and renal transplants each year, the dental hygienist needs to understand the disease and the related problems that can be encountered in providing dental care. The types of kidney diseases as well as the types of dialysis are reviewed. Dialysis can cause dental complications which include prolonged bleeding, candidial infections, and xerostomia as well as others. It is important that the hygienist know what problems can arise and the solutions for them. PMID- 2600639 TI - Sexual discrimination in academia. Implications for dental hygiene faculty. AB - Despite anti-discriminatory legislation, academic women in the 1980s have not achieved equality, and continue to face diverse problems advancing in an academic system based on a patriarchal paradigm. The purpose of this paper is to provide dental hygiene faculty with insight, awareness, and understanding into four major problem areas that influence women's academic success: values and attitudes learned through socialization; blocks to administrative positions; the male locus of decision making; and double standards of performance evaluation. Additionally, examples of solutions to these problems are discussed in three categories: individual, internal to the university, and external to the university; in an effort to better prepare women in dental hygiene education to succeed in academia despite discriminatory practices. PMID- 2600640 TI - Variables that predict success on the National Board Dental Hygiene Examination. AB - The purpose of this research was to determine which, if any, of students' academic variables (high school grade point average [GPA], ACT scores, grades in college biological, physical, and behavioral sciences, dental hygiene GPA and college cumulative GPA as well as demographic variables [age and marital status]) were useful in predicting a passing score on the National Board Dental Hygiene Examination (NBDHE). The entire population of 1983-86 graduates from three associate degree granting dental hygiene programs (N = 219) served as subjects. Information was obtained from the students' records retained at the schools. The research showed that grades in college anatomy, nutrition, sociology, chemistry, and physiology are the best predictors of the dental hygiene GPA. The best predictors of pass/fail status on the NBDHE are dental hygiene GPA, ACT social studies, sociology, general psychology, and anatomy. PMID- 2600641 TI - Survey of recall systems in dental hygiene programs. AB - A nationwide survey of the United States' 198 dental hygiene educational programs was conducted to determine the existence and type of clinical recall systems in the educational setting. Several factors contributing to recall systems were examined including program demographics, type and administration of the recall system, and patient acquisition and distribution. Responses were received from 177 educational programs, yielding a response rate of 89.4%. Approximately 85% of the programs responding utilize a recall system. Results indicate that the majority of programs do not employ a specific type of recall format. Preferred combinations of key individuals responsible for the administrative duties associated with the recall system include the clinic supervisor, students, and/or program secretary. Distribution of recall patients to students as needed, with variable intervals for recall, is promoted by the majority of respondents. PMID- 2600642 TI - Nature and scope of changes in predoctoral dental education standards. PMID- 2600643 TI - Effects of specific criteria and calibration on examiner reliability. AB - The purpose of this pilot study was to investigate the use of specific criteria and examiner calibration on the reliability of inexperienced examiners on dental sealant evaluations. Dental (N = 8) and dental hygiene (N = 8) students participated as examiners. The study objectives were to identify differences in calibrated and non-calibrated examiners, examiners calibrated by an expert or non expert, and reliability between dental and dental hygiene student examiners. A criterion-referenced evaluation form was used to evaluate dental sealant end product on 20 teeth, twice by each examiner. Eight of 16 examiners participated in a one-hour calibration session between evaluations. The session consisted of a discussion of operational definitions, the evaluation procedure for dental sealants, and use of the criterion-referenced form. Intra- and interexaminer reliabilities were measured. There were no statistically significant differences (p less than .05) in intraexaminer reliability. Although calibration produced no significant increase in interexaminer reliability, the post-training reliability scores for the group calibrated by an expert decreased, and scores for the group calibrated by a non-expert increased. No significant difference was found in reliability between dental and dental hygiene student examiners. PMID- 2600644 TI - Cognitive-behavioral psychology and oral hygiene. A new perspective on an old problem. AB - This article describes the application of learning principles derived from behavioral and cognitive psychology to oral hygiene. It reviews the theoretical basis of a plaque prevention approach based on psychological models of self control behavior. This approach was derived from research on learning environments, interviewing, behavior modification, and cognitive psychology. PMID- 2600645 TI - Dental hygienists' performance of procedures emphasized in school. Frequency and barriers. AB - In the educational setting, dental hygiene students learn to perform a variety of clinical procedures. Some procedures regularly performed in the school clinical setting may not be practiced regularly in the employment setting. If students learn to value the necessity of performing these procedures, why does this disparity between school and practice exist? This study examined how frequently dental hygienists who have graduated from a baccalaureate program perform certain dental-related preventive/diagnostic procedures in practice that are regularly required with school clinical patients. Barriers to performing the procedures are identified, as well as the hygienists' feelings about not performing the procedures. PMID- 2600646 TI - Supervision and practice of dental hygienists: report of ADHA survey. AB - In 1986, the American Dental Hygienists' Association (ADHA) funded a study to examine demographic and practice data concerning the dental hygiene profession. The purpose of this survey was to establish a data base for the current practice of licensed dental hygienists in the United States. Information was collected on the type of supervision under which hygienists worked and the type of supervision they would prefer. Using a stratified random sampling technique, questionnaires were sent to licensed member and nonmember dental hygienists residing in the United States. A total of 9,110 hygienists received surveys and after a second mailing to nonrespondents, a total of 4,522 completed surveys were received, for a response rate of 49.6%. This survey indicates that hygienists' attitudes toward supervision are changing. Although the majority of hygienists still work in a private practice where a dentist is present and usually examines the patient, over half of the respondents prefer that the dentist's presence in the facility not be required. In examining practice behaviors, a collaborative relationship appears to exist between the hygienist and dentist when treating both new and recall patients. The collaborative relationship decreases with the dental hygienist demonstrating an increase in responsibility and independent decision making for recall patients. Traditional practice behaviors are also changing to include more comprehensive dental hygiene services, particularly by baccalaureate degree hygienists. PMID- 2600648 TI - Evaluation of canal finder system for root canal instrumentation. PMID- 2600647 TI - Office profile. AB - A national study was conducted by the American Dental Hygienists' Association (ADHA) in 1986, to examine several variables related to dental hygiene practice. Questionnaires were sent to both ADHA members and nonmembers with a response rate of 49.6%. The 4,013 hygienists who responded to this survey answered 80 questions, six of which related to office profile and are reported in this paper. The responses concerning state of practice, community size, practice setting, number of office personnel, number of hours worked, and age characteristics of patients are included. Results indicate that most hygienists work primarily in traditional dental practices, live in metropolitan areas, and are most likely to treat a majority of patients between the ages of 19 and 44. Seventy-one percent of the hygienists work 20 hours or more per week and the mean number of hours worked per week is 32. This indicates that most dental hygiene practitioners work full-time. PMID- 2600649 TI - An epidemiologic study of the oral health status of high school students in New Jersey. AB - This study was performed in order to record the prevalence of tooth decay in high school students in New Jersey. During the Spring of 1986, 3,556 students, aged 13 to 18 years, in 8 public high schools in 7 communities, participated in the study. The subjects were examined by 3 trained examiners with mirror, explorer, air syringe and overhead auxiliary light. A lesion was recorded as dental caries if there was a perceptible break in the enamel surface. Questionable incipient areas were not recorded as carious lesions. Mean DMFT was found to be 4.17 +/- 3.7 and mean DMFS was 7.02 +/- 7.4. Hispanic subjects had more decay (DMFT 4.98, DMFS 9.03) than black subjects (DMFT 4.13, DMFS 6.94) and white subjects (DMFT 3.53, DMFS 5.43). Females had more decay (DMFT 4.51, DMFS 7.67) than males (DMFT 3.79, DMFS 6.33). Hispanic and black subjects also had more untreated decay (24 and 22 percent decayed of the DMFT) compared with only 11% untreated decay in white subjects. Socioeconomic level was inversely related to caries activity; however, geographic location of the school within the state (north versus south) was not a factor. PMID- 2600650 TI - The geriatric patient: evaluation, treatment planning, affordable concepts. AB - The predicted growth of the geriatric population mandates the health professional to turn their attention to treatment modalities which are indicated for this particular cohort. The dentist must examine, evaluate and treatment plan these patients with a systematic approach. Guidelines are offered to expedite the care of the elderly both efficiently and cost effectively. PMID- 2600651 TI - Solving problems: down the yellow brick road. PMID- 2600652 TI - A comprehensive system to enhance the staff role in patient education. AB - This article describes the development and implementation of a comprehensive system to support the staff nurse's role in patient education. An overview of the content and process of a two-part workshop is presented. The system used for documenting, disseminating, filing, and revising patient education programs is discussed. The ways this system have enhanced patient education and staff satisfaction are described. This system can be used to enhance the efficiency and effectiveness of patient education in any health-care setting. PMID- 2600654 TI - An innovative approach to orientation: faculty preceptors. AB - The Faculty Summer Preceptor Program was instituted in the summer of 1987 to assist with the orientation of more than 200 newly employed graduate nurses at Thomas Jefferson University Hospital in Philadelphia. Plans had to be made to assist the staff in assimilating this large number of orientees without disrupting patient care delivery. Preceptorships were used extensively in nursing services during the past 10 years. A major advantage of using faculty is that they are very familiar with new graduates' skills, anxieties, and needs, and the faculty role closely corresponds with the role of the preceptor. The faculty is a "ready made" resource for nursing staff orientation. PMID- 2600653 TI - The LPN-ADN articulation project. AB - Faced with a staffing situation where RN positions were needed but there were more LPN positions than were needed. Tucson Medical Center began an LPN-ADN articulation project to rectify the situation without resorting to layoffs. With the cooperation of a local junior college, LPNs are enrolled in ADN programs that provide a more flexible work/study situation. This article describes the program and the results thus far. PMID- 2600655 TI - Budgeting from bedside to boardroom. A staff development course. AB - This article describes a course designed for use by staff development departments that incorporates the information and skills needed for staff nurses and nurse managers to become contributing partners in the financial planning management of their units, their division, and their organization. The delicate balance between the delivery of quality care and corporate economic stability can best be fostered by knowledgeable practitioners and administrators who share a common philosophy of care giving and fiscal accountability. PMID- 2600656 TI - Creative methods of meeting JCAHO inservice requirements for hospital staff. PMID- 2600657 TI - Competency-based orientation. PMID- 2600658 TI - Evaluation and/or research? PMID- 2600659 TI - Intestinal absorption of stearic acid after consumption of high fat meals in humans. AB - The intestinal absorption of stearic acid (18:0), relative to other fatty acids, was evaluated in a group of 10 normal volunteers. Subjects were fed two types of high fat meals; one contained a relatively high content of stearic acid and the other a relatively low content. Plasma chylomicrons were isolated at 2, 4, 6 and 8 h after ingestion of the meals. Fatty acid patterns of chylomicron lipids were determined, and relative intestinal absorption rates of each fatty acid were estimated by comparing the fatty acid composition of chylomicron lipids with that of the fat in the meals. Overall, for both meals the fatty acid pattern of chylomicron lipids was very similar to that of ingested fat. Percentages of palmitic acid (16:0) and stearic acid, relative to other fatty acids, were only slightly lower in chylomicron lipids than in the meal fat. These data suggest that intestinal absorbability of stearic acid is similar to that of palmitic acid, and both saturated fatty acids appear to be absorbed almost as well as oleic acid (16:1). PMID- 2600660 TI - Effects of dietary fatty acid composition on macronutrient selection and synaptosomal fatty acid composition in rats. AB - Our previous work showed that rats consuming 20% (wt/wt) lard diets selected more protein and less carbohydrate than did rats fed 20% (wt/wt) soybean oil diets. To determine if this effect is specific to saturated fat source and to measure changes in fatty acid composition of synaptosomal phospholipids, male Wistar rats were fed a 20% (wt/wt) soybean oil or tallow diet with 24% protein and 48% carbohydrate for 2 wk. Rats then self-selected from two diets with the same fat previously fed but different protein and carbohydrate composition (5% protein, 67% carbohydrate and 55% protein, 17% carbohydrate). Tallow-fed rats selected more protein and less carbohydrate than did soybean oil-fed rats. Dietary fat also affected fatty acid composition of synaptosomal phospholipids, phosphatidylcholine being most affected and phosphatidylinositol most resistant. Later studies determined if selection differences were due to taste. When rats self-selected without prior exposure to diets, tallow-fed rats selected more protein and less carbohydrate than did soybean oil-fed rats during the last 2 wk but not the first 2 wk. When rats selected from diets with identical protein and carbohydrate composition but different dietary fat, rats consumed slightly greater amounts of the tallow diet at each protein level. The relative intake of tallow and soybean oil diets, however, did not vary significantly with dietary protein treatment. These results confirm that rats fed saturated fat diets select more protein and less carbohydrate than do rats fed polyunsaturated fat diets and suggest this difference is not due to taste factors. PMID- 2600661 TI - A comparison of the digestion and absorption of cocoa butter and palm kernel oil and their effects on cholesterol absorption in rats. AB - Digestion and absorption of cocoa butter and palm kernel oil and their effect on cholesterol absorption were studied in adult male rats. Duodenal and thoracic duct catheters were inserted surgically into the anesthetized rats. After an overnight fast, animals were given a single duodenal dose of an aqueous emulsion containing [1,2-3H]cholesterol and one of the following: corn oil, cocoa butter or palm kernel oil. Digestion and absorption were estimated by recovering the total fatty acids in the thoracic duct lymph over a 24-h collection period (after subtraction of the baseline "endogenous fatty acids" in the lymph). Intestinal absorption of cholesterol into the thoracic duct lymph was reduced significantly (P less than 0.05) in the presence of cocoa butter, compared to absorption when palm kernel oil or corn oil was administered. Compared to the absorption of corn oil (arbitrarily defined as 100%), the absorption of palm kernel oil and cocoa butter was 82 and 63%, respectively. The present study suggests that palm kernel oil absorption was not significantly different from that of corn oil. The lower absorbability of cocoa butter and its inhibitory effect on cholesterol absorption may explain in part why cocoa butter is less hypercholesterolemic and atherogenic than other equally saturated fats. PMID- 2600662 TI - Effect of dietary lipids and vitamin E on in vitro lipid peroxidation in rat liver and kidney homogenates. AB - Rats were fed for 5 wk 10% (wt/wt) menhaden oil (MO) or a 10% corn oil-lard (COL) mixture (1:1) in diets with a low vitamin E content (less than or equal to 5 mg/kg) or supplemented with d-alpha-tocopheryl succinate to a total of 30 or 150 mg per kg. Thiobarbituric acid-reactive substances (TBARS), conjugated dienes (CD), hexanal and total volatiles (TOV) were measured in tissue homogenates incubated at 37 degrees C for 1 h in the absence (uninduced) and presence of 15 microM ferrous sulfate (induced). The fatty acid composition of liver and kidney reflected that of dietary lipids. For uninduced peroxidation, there was in general a significant inverse correlation of TBARS, CD and TOV with the log of dietary vitamin E content for liver and kidney from rats fed either lipid. For induced peroxidation, the inverse correlation was significant for liver, but not for kidney, from rats fed either lipid. The correlation was generally higher for liver and kidney from rats fed COL than for tissues from rats fed MO. Vitamin E was thus a more effective antioxidant for liver than for kidney regardless of the dietary lipid, and for liver and kidney from rats fed COL than from rats fed MO. Dietary MO enhanced tissue susceptibility to both peroxidation systems. A simulation model developed to mimic the experiments showed good correlations between experimental data and simulated values. PMID- 2600663 TI - Plasma and brain ammonia and amino acids in rats measured after feeding 75% casein or 28% egg white. AB - Male rats were trained to consume their daily food intake in 3 h. When rats were fed 6% casein for 14 d and were then fed either the 6 or 75% casein diet for 1 d, the plasma and brain ammonia concentrations of rats fed 75% casein were higher (P less than 0.05) at 23 h after test meal initiation compared to those of rats fed 6% casein. When rats were fed 6% casein for 13 d and then fed the same 6% casein diet with or without an additional 15% ammonium acetate for an additional 7 d before feeding 75% casein for 1 d, the plasma ammonia concentration of each group was not different, but plasma and brain amino acid concentrations were lower in rats prefed 15% ammonium acetate before the 75% casein diet. When rats were fed 6.8% egg white for 9 d and then fed 27.9% egg white for an additional 7 d, food intake of rats fed the 27.9% egg white diet was lower (P less than 0.05, paired t test) for 4 d compared with that during the 3-d pretest period. When rats were meal-fed the 6.8% egg white diet for 13 d and then fed either the same 6.8% egg white diet or the 27.9% egg white diet for 1 d, plasma ammonia and plasma and brain amino acid concentrations were higher at 5 h after test meal initiation (P less than 0.05) in rats fed 27.9% egg white compared to those of rats fed 6.8% egg white. At 23 h after test meal initiation, plasma ammonia, plasma amino acid and most brain amino acid concentrations were lower than they were at 5 h after test meal initiation in rats fed 27.9% egg white. PMID- 2600664 TI - Hepatic cysteine sulfinic acid decarboxylase activity in rats fed various levels of dietary casein. AB - A series of experiments was conducted to examine the effects of dietary protein intake on hepatic cysteine sulfinic acid decarboxylase (EC 4.1.1.29) activity and urinary taurine excretion. When rats were fed diets containing 18, 30, 45 or 60% casein for 1 wk, hepatic cysteine sulfinic acid decarboxylase activity (CSAD) decreased in a progressive and significant manner. Enzyme activity in rats fed a 60% casein diet was 25% of the activity measured in rats fed 18% casein. The time course of the change in CSAD activity was examined in rats fed a 60% casein diet. Within 24 h of switching rats from a moderate (18% casein) to high (60% casein) protein diet, enzyme activity decreased by 50% and continued to decline in rats fed the high protein diet for 7 d. The observed decrease in enzyme activity was reversed when rats were refed the 18% casein diet. The half-life of CSAD was calculated to be 2 and 7 d during the diet switch from 18 to 60% casein and from 60 to 18% casein, respectively. The change in enzyme activity was evident after a single high protein meal. In contrast to CSAD activity, urinary taurine excretion increased 140-fold within 2 d of switching rats from an 18 to 60% casein diet. Upon refeeding of the 18% casein diet taurine excretion rapidly decreased. These findings indicate that CSAD responds in a rapid and reversible manner to dietary protein. PMID- 2600665 TI - Pancreatic response in rats and mice to trypsin inhibitors from soy and potato after short- and long-term dietary exposure. AB - The effects on the pancreas of chronic (95 wk) dietary exposure to protease inhibitors from soy and potato were compared in rats and mice. Soy and potato trypsin inhibitor (TI) concentrates were prepared from defatted raw soy flour and potato juice, respectively, by selective precipitation and ultrafiltration. Animals were fed a diet in which casein supplied approximately 20% protein. Each concentrate (less than 1% of the diet) was added to provide 100 and 200 mg of trypsin inhibitor activity per 100 g of diet. In short-term (28 d) experiments in rats, both sources of TI decreased the apparent nutritional quality of casein and produced pancreatic hypertrophy consistent with a hormonally mediated feedback mechanism for pancreatic adaptation to diet that is interactive with the nutritional status of the animal. After long-term feeding (95 wk), soy and potato TI produced dose-related pancreatic pathology in rats consisting of nodular hyperplasia and acinar adenoma, which was typical of that associated with raw soy flour. Although mice responded similarly to rats to soy TI in short-term (28-d) feeding experiments, they were resistant to the formation of these lesions following long-term feeding. This considerable species variation in propensity to develop preneoplastic and neoplastic lesions of the pancreas is not predicted by the short-term hypertrophic and hyperplastic response of the pancreas to TI. PMID- 2600666 TI - Consumption of raw potato starch alters intestinal function and colonic cell proliferation in the rat. AB - Raw potato starch (RPS) may escape complete digestion to enter the colon and produce alterations in colonic function, while cooked potato starch (CPS) is nearly completely digested in the rat small intestine. Effects of RPS and CPS on colonic function [fecal weight, transmit time and thymidine kinase (TK) activity (a marker for cell proliferation)] were contrasted in a 6-wk feeding study. Male F344 rats consumed either dextrose/sucrose (DS; control), 30% CPS or 30% RPS diet. RPS feeding resulted in a 3-fold increase in fecal weight and a 30% prolongation in transit time, as well as elevated levels of colonic mucosal total protein (50%) and TK activity (4- to 7-fold) compared to DS-fed rats. A second study revealed normal large intestinal histology in rats fed CPS or RPS, with elongated colonic crypts (33% increased over CPS) in group RPS. Large intestinal contents were heavier in group RPS than in group CPS. These studies demonstrate that RPS feeding significantly enhances fecal weight yet prolongs total gastrointestinal transit time. Enhanced colonic TK and elongated colonic crypts suggest that RPS stimulates colonic mucosal growth. PMID- 2600667 TI - Effect of dietary fat, starch and cellulose on fecal bile acids in mice. AB - The effect of dietary fat, starch and cellulose on individual and total fecal bile acids was studied in mice after 4 wk of feeding diets containing different levels of fat (5 and 29%), starch (3, 36 and 57-65%) and cellulose (2 and 10%). Diet affected the fecal concentration of deoxycholic acid, beta-muricholic acid and total bile acids. Increasing dietary fat from 5 to 29% significantly increased the level of deoxycholic acid and total bile acids. An increase in dietary cellulose from 2 to 10% significantly decreased the level of deoxycholic acid, beta-muricholic acid and total bile acids. High levels of dietary starch (36 and 57-65%) did not significantly affect the excretion of deoxycholic, beta muricholic and total fecal bile acids. Starch was able to bind bile acids in vitro and to affect the level of fecal free bile acids. In high fat diets, the level of free bile acids was lower in the feces of animals fed 36% starch diets than in those fed 3% starch diets. This reduction of free bile acids was accompanied by a reduction in colon proliferative activity. We suggest that free, rather than total, bile acids are the effective damaging agents for colon mucosa, and may represent a risk factor in the development of cancer. PMID- 2600668 TI - Effects of ergocalciferol supplementation on the concentration of vitamin D and its metabolites in human milk. AB - The effect of maternal ergocalciferol (vitamin D2) supplementation on the concentrations of vitamin D, 25-hydroxyvitamin D (25-OH-D), 24R,25 dihydroxyvitamin D [24,25-(OH)2D], and 1 alpha,25-dihydroxyvitamin D [1,25 (OH)2D] in their milk was studied. Vitamin D2, D3, 25-OH-D2 and 25-OH-D3 were simultaneously determined by high performance liquid chromatography, and the determination of 24,25-(OH)2D and 1,25-(OH)2D was performed by competitive protein binding assay and radioreceptor assay, respectively, after separation of the D2 and D3 compounds. After healthy lactating mothers had received a daily oral dose of vitamin D2 (1,200 IU/d) for 4 wk, the concentrations of vitamin D2, D3 and the metabolites were determined in their plasma and milk. Although the plasma levels of 25-OH-D2 were significantly increased, the increase in milk was relatively small. On the other hand, the increase of vitamin D2 levels in milk was greater than that of 25-OH-D2 in milk after supplementation. The levels of 1,25-(OH)2D in milk was lower after 5 wk of lactation than after 1 wk of lactation, regardless of maternal vitamin D2 supplementation. When total antirachitic activities in milk were calculated, only a very slight increase was observed as a result of supplementation. PMID- 2600669 TI - Effect of low zinc intake on absorption and excretion of zinc by infants studied with 70Zn as extrinsic tag. AB - The effect of low dietary intake of zinc was studied in six normal infants with the use of 70Zn as an extrinsic tag. Of the two study formulas, one provided a zinc intake similar to that of customary infant formulas ("high" intake), whereas the other provided a "low" zinc intake. Two zinc absorption studies were performed with each formula (sequence: high-low-low-high). Extrinsically labeled formula was fed for 24 h and excreta were collected for 72 h. Zinc isotope ratios were determined by inductively coupled plasma mass spectrometry (ICP/MS). When zinc intake was high, net zinc absorption was 9.1 +/- 8.7% (mean +/- SD) of intake and net zinc retention was 74 +/- 91 micrograms/(kg.d). True zinc (70Zn) absorption was 16.8 +/- 5.8% of intake and fecal excretion of endogenous zinc was 78 +/- 56 micrograms/(kg.d). When zinc intake was low, net absorption of zinc increased significantly (P less than 0.001) to 26.0 +/- 13.0% of intake, but net retention was not significantly different at 42 +/- 33 micrograms/(kg.d). True absorption of zinc also increased significantly (P less than 0.001) to 41.1 +/- 7.8% of intake, whereas fecal endogenous zinc decreased (P less than 0.05) to 34 +/- 16 micrograms/(kg.d) during low zinc intake. Thus, infants maintain zinc balance in the face of low zinc intake through increased efficiency of absorption and decreased excretion of endogenous zinc. PMID- 2600670 TI - Effect of zinc deficiency and food restriction in rats on erythrocyte membrane zinc, phospholipid and protein content. AB - Zinc deficiency in rats increases the osmotic fragility of erythrocytes, suggesting a structural defect in the plasma membrane. The purpose of this study was to determine the effect of zinc deficiency on membrane components that might be responsible for the increased fragility. Immature male rats were fed for 3 wk a zinc-deficient (0.5 mg Zn/kg) or a control (100 mg Zn/kg) diet either ad libitum or pair-fed. Red blood cell membranes were analyzed for zinc after wet ashing in nitric-perchloric acid. The fatty acid composition of membrane phosphatidylcholine and phosphatidylethanolamine was determined by gas-liquid chromatography, and the protein composition was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The membrane zinc concentration was decreased by zinc deficiency, but returned to control levels upon repletion with a zinc-adequate diet for 3 d. The increased osmotic fragility was also restored to the control level during the same repletion period, suggesting that zinc is an important determinant of membrane stability. The phospholipid fatty acid composition was altered by zinc deficiency, but these changes were not rapidly reversed by repletion. The membrane cholesterol:phospholipid ratio was also increased by zinc deficiency. Zinc status had no influence on the membrane protein profiles of the components visualized by staining. Only the concentration of membrane zinc correlated with osmotic fragility during zinc depletion and repletion. PMID- 2600671 TI - Intrinsic and extrinsic stable isotopic zinc absorption by infants from formulas. AB - The kinetics of fecal elimination and the extent of fractional absorption of intrinsic and extrinsic zinc from infant formula were studied in 11 human infants by using a direct, simultaneous dual-label method based on fecal monitoring of unabsorbed stable isotope labels. The relative positions of the two stable isotopic tags (67Zn, 70Zn) as extrinsic and intrinsic labels were reversed in two separate determinations of fractional absorption. Administration of doubly labeled formula for 24 h or less permitted elimination of unabsorbed labels before the end of a 72-h metabolic interval. The extent of enrichment and the kinetics of fecal elimination of unabsorbed extrinsic stable isotopic zinc tag were observed to agree closely with the corresponding values for the intrinsic tag. Fractional absorption of intrinsic and extrinsic tags was highly correlated and did not differ significantly. The ratio of fractional absorption of extrinsic tag to that of intrinsic tag was 1.05 +/- 0.19 (mean +/- SD). The results constitute strong support for validation of the use of enriched stable isotopes at low levels (less than or equal to 10%) of extrinsic addition to milk-based diets for studies of zinc absorption by humans. PMID- 2600672 TI - Aqueous ethanol extraction of dietary soy protein isolate improves 59Fe absorption by the rat from a casein-based test meal. AB - A commercial soy protein isolate (SPI) was further processed in an attempt to understand how a diet based on SPI can cause decreased iron retention by the rat from a separately administered casein-based test meal. Groups of eight rats were fed either a casein-based diet or a diet based on SPI. The acid-precipitated SPI was incorporated into diets as such, after neutralization, after 60% (v/v) ethanol extraction and neutralization, or after 60% ethanol exposure and neutralization. All dietary SPI was heat-treated by exposure to steam at 108 degrees C for 30 min. Rats were fed their respective diets, each containing 25 mg Fe/kg, for 13 d, and then all rats were fed a 59Fe-radiolabeled 2.5-g casein test meal containing 64 micrograms of iron. Ingested radioactivity was determined following the meal, and retained radioactivity over the subsequent 10-d period. Absorption was not distinguishable for groups fed the casein-based (78.3 +/- 3.6%) and the ethanol-extracted, SPI-based diet (80.2 +/- 5.4%). Absorption was lower (P less than 0.01) for groups fed each of the other SPI-based diets: SPI as such (68.3 +/- 8.9%), neutralized SPI (69.8 +/- 5.0%) and ethanol-exposed SPI (67.6 +/- 4.8%). An ethanol-extractable component of SPI may be responsible for decreased iron absorption by animals fed SPI prior to a radiolabeled test meal. PMID- 2600673 TI - Calculations of the distribution of zinc in a computer model of human serum. AB - During the last decade, investigators employing a wide variety of separation techniques have reported that serum albumin, rather than serum transferrin, is the major carrier protein for labile zinc. However, in contrast to these studies, a simple comparison of the zinc binding constants for albumin and transferrin suggests a significant role for transferrin with regard to serum zinc transport. In the present study multicomponent equilibrium calculations that incorporate recently determined binding constants for zinc-transferrin as well as equilibrium constants for the binding of bicarbonate, sulfate and phosphate to apotransferrin have been used to model the distribution of labile zinc in normal human serum. Anion binding has a major impact on the predicted zinc distribution, lowering the percentage of zinc bound to transferrin from 56% to 11%. The model gives approximately 1% zinc as low-molecular-weight complexes. The improved model results are in good agreement with biological studies on the distribution of zinc among serum proteins. PMID- 2600674 TI - Interactions of lactose with calcium, magnesium and zinc in rats. AB - The effects of lactose on utilization of calcium, magnesium and zinc were examined in two studies. In study 1, weanling male rats were fed either nonfat dry milk or CaHPO4, dolomite or a calcium chelate with supplemental lactose or sucrose for 27 d. In study 2, weanling male rats were fed diets based on milk or lactose-hydrolyzed milk for 28 d or in one meal labeled with 45Ca. Rats fed the lactose-hydrolyzed milk rather than the untreated milk digested their diet more completely, apparently absorbed total calcium and 45Ca less efficiently, and lost more calcium in urine but retained similar amounts of total calcium and 45Ca in bone. The effect of lactose hydrolysis on the absorption of 45Ca was similar whether rats were fed only one meal of the milk-based diets or were fed the diets chronically. The rats fed supplemental lactose (study 1) or unhydrolyzed milk (study 2) retained more magnesium and zinc in bone. PMID- 2600675 TI - Dietary phenolic compounds: inhibition of Na+-dependent D-glucose uptake in rat intestinal brush border membrane vesicles. AB - The effects of phenolic compounds on Na+-dependent D-glucose transport were investigated in brush border membrane vesicles isolated from rat small intestine. Screening experiments were conducted with different classes of phenolic compounds in both their native and oxidized forms. Pretreatment of vesicles with tannic acid (1 mg/ml) completely abolished the characteristic overshoot of active glucose accumulation. With chlorogenic acid (1mM), 80% of the glucose transport capacity was lost. Reductions of 30-40% were observed in vesicles treated with catechin, ferulic or caffeic acids. Treatment with gallic acid (1 mM) had little effect. Phenolic oxidation state did not exacerbate the degree of glucose transport inhibition, with the exception of catechol (1 mM), which gave maximal inhibition (86%) in its oxidized form. Gradient-independent glucose uptake was not altered, nor did phenolic treatment increase nonspecific binding of glucose to the membrane vesicles. Possible mechanisms of D-glucose transport inhibition were examined in chlorogenic acid-and tannic acid-treated vesicles. Factors such as alterations in vesicle permeability, size and leakage of transported glucose out of the vesicles were ruled out. Measurements of D-glucose uptake under conditions of Na+ equilibrium suggest that tannic and chlorogenic acids reduce glucose uptake by favoring the dissipation of the Na+ electrochemical gradient, which provides the driving force for active glucose accumulation. PMID- 2600676 TI - Effect of L-carnitine on glycogen synthesis and ATP production in cultured hepatocytes of the newborn rat. AB - Changes in intracellular carnitine, ATP and glycogen concentration were studied when hepatocytes of newborn or adult rats were incubated with oleate, lactate and/or carnitine. Hepatocytes of adult rats appeared to be able to maintain cellular carnitine concentration without exogenous carnitine supplementation. Hepatocytes of newborn rats appeared to be unable to maintain cellular carnitine concentration without carnitine supplementation. Moreover, ATP concentration and glycogen concentration were significantly increased by the carnitine supplement with oleate and/or lactate compared to the unsupplemented group. Increases in both intracellular ATP and carnitine concentration depended on the concentration of carnitine added to the medium. These results suggest that carnitine may be an important factor in glycogen synthesis and ATP production of newborn infants. PMID- 2600677 TI - Effects of litter size and diet composition on the development of some lipogenic enzymes in the liver and brown adipose tissue of the rat. AB - Male Sprague-Dawley rats were reared in litters of nine (normal litters) or 18 pups, and the dams were fed either a low fat (control) or a high fat diet. Offspring from each litter size and diet group were separated from the mothers on postnatal d 30, subdivided into two groups each, and fed either the control or the high fat diet until postnatal d 77. Hepatic glucose-6-phosphate dehydrogenase, malic enzyme and ATP-citrate lyase activities in the offspring from large litters were elevated during the early stages of weaning but later lagged behind enzyme activity of the normal litters. Brown adipose tissue enzymes also surged earlier in rats from large litters but did not fall below the values attained by the normal litters until postnatal d 32. Enzyme activities on postnatal d 77 revealed that large litter size and high fat feeding during or after weaning were associated with diminished hepatic enzyme activities. Hepatic glucose-6-phosphate dehydrogenase and ATP-citrate lyase activities also showed significant positive interaction between litter size and diet composition after weaning. Large litter size was also associated with diminished brown adipose tissue enzymes in the mature rats, but the composition of the weaning diet did not independently exert long-lasting changes in this tissue. Nevertheless, there was a positive interaction between litter size and diet composition during and after weaning. The data suggest that neonatal undernourishment can exert a long term influence on the metabolic profiles of the animal, and that diet plays a role in modulating this influence. PMID- 2600678 TI - Whole rat embryos require methionine for neural tube closure when cultured on cow serum. AB - Headfold-stage rat embryos, when cultured on cow serum without supplemental methionine, failed to close their neural tubes, lacked eyes and branchial arches, were abnormally shaped and were reduced in protein content compared to methionine supplemented embryos. Methionine was essential during the first 18 h of culture, a period in which neural tube closure was initiated in supplemented cultures. All cow serum samples tested were found to require methionine addition, and the methionine was not replaced by other amino acids or vitamins, including folate. Methionine was not toxic to cultured rat embryos at concentrations up to at least 500 micrograms/ml. Analyses of serum free amino acids revealed lower levels of free methionine in cow serum compared to rat serum, and cow serum proteins contained less methionine relative to other amino acids than did rat serum proteins. Dialysis of cow serum reduced but did not eliminate the requirement for methionine. This suggested either that the free amino acids of cow serum were imbalanced or that a dialyzable component in serum interfered with the availability/utilization of methionine. Dietary supplementation of cows with rumen-protected DL-methionine increased the serum methionine level, and serum drawn from supplemented cows supported normal rat embryo development without additional methionine. PMID- 2600679 TI - Effects of native and oxidized phenolic compounds on sucrase activity in rat brush border membrane vesicles. AB - The effects of dietary phenolic compounds on intestinal sucrase were investigated in brush border membrane vesicles purified from rat small intestine. Screening experiments were conducted with different classes of phenolic compounds in both oxidized and native forms. The most potent inhibitor was native tannic acid at 0.1 mg/ml, resulting in an 80% loss of activity. Oxidized tannic acid had no effect. Significant decreases were also observed in vesicles treated with 0.1 mg/ml of catechol or epicatechin, yielding activity losses of 30-50%, regardless of oxidation state. With gallic acid, maximal (40%) inhibition occurred only in the oxidized form. Other phenolic compounds, such as ferulic, p-coumaric and caffeic acids, tended to be slightly inhibitory, while no inhibition was observed with vanillin or chlorogenic acid at the concentrations tested. These results confirm the enzyme inhibitory action of tannic acid, a polyphenolic compound, and also demonstrate that some individual dietary phenolic monomers have the potential to modulate enzyme activity in a brush border membrane vesicle model system. PMID- 2600680 TI - Digestion and absorption of fish oil by neonatal piglets. AB - In order to establish the digestibility and absorption of fish oil, 18 unsuckled, newborn piglets were tube-fed an amount of fish oil calculated to provide the piglets' maintenance energy needs for 12 h. After fat administration the piglets were either intubated with 25 ml of fat-free milk replacer per h, or fasted. The digesta of the stomach, small intestine, and large intestine (digesta plus feces) were collected 12 h after fish oil intubation. Disappearance of total extractable fat was 95 +/- 1 and 94 +/- 1% for fed and fasted piglets, respectively. True absorption of the lipid was calculated from the disappearance of eicosapentaenoic acid and was 99% for both fed and fasted piglets. Nearly 50% of the stomach lipid was as diglycerides and free fatty acids, suggesting that hydrolysis of the fish oil was initiated in the stomach. Small intestinal lipid was 63-65% free fatty acids, indicating that the piglet pancreatic lipase was of sufficient activity to hydrolyze fish oil triglyceride. Neonatal piglets appeared to have ample capacity to digest and absorb fish oil, which supports the concept that lipid supplementation could improve the energy status of the newborn piglet. PMID- 2600682 TI - Legal issues of ethical decision making. PMID- 2600683 TI - The ethics survey: an important step in promoting nursing ethics. AB - A needs analysis survey tool was developed to determine the nature and type of ethics-related activities needed by nurses in a large urban medical center. The survey revealed that nurses' self-assessed need was, first, for staff development and, second, for an ethics consultation service. PMID- 2600681 TI - Ethics committees in health care institutions in the New York City metropolitan region: a report of two nursing surveys. AB - Two surveys were conducted independently to ascertain whether health care institutions in the New York City metropolitan region currently have ethics committees and to gather information related to their functioning and use by nurses. Comparable findings in the overlapping samples suggest that approximately one-third of surveyed institutions do not have interdisciplinary ethics committees. Where the committees do exist, they may not be adequate to address nurses' ethical concerns. PMID- 2600684 TI - Critical care nurses' participation in ethical decision making. AB - Critical care staff nurses' participation in ethical decision making was studied in relation to the perceptions of environmental social support of 45 female staff nurses. Data obtained measured perceived environmental social support from six organizational subgroups and individual participation in ethical decision making. Validity and reliability testing was done on the instrument. When involved in an ethical situation, critical care nurses perceived low levels of environmental social support from hospital administrators, nursing administrators, and physicians. Co-workers were consistently perceived as most supportive across all aspects of social support. The majority of the nurses surveyed (74%) reported that ethical decisions were made by physicians or with reference to hospital policy, and that there were limited roles for individual, family, or nurse participation in such decision making. It was concluded that critical care nurses perceive a lack of free agency necessary to engage in ethical decision making in hospital environments or to act in an advocacy role in such situations. PMID- 2600686 TI - Relation of somatic symptoms to degree of paternal-role preparation of first-time expectant fathers. AB - This study was conducted to determine the association between the presence of somatic symptoms (couvade syndrome) and the amount of paternal-role preparation attained by 64 expectant fathers. Thirty-five men in the sample identified more than two symptoms; most frequently, restlessness, increased appetite, and difficulty sleeping. Men experiencing symptoms scored higher on scales measuring paternal-role preparation than men not experiencing symptoms. PMID- 2600685 TI - Self-confidence as a critical factor in breast self-examination. AB - This study was conducted to determine predictors of breast self-examination (BSE) frequency. One hundred ninety-one women completed questionnaires about their personal experiences with BSE, their risk factors, and their perceived risks of breast cancer. Satisfaction with BSE ability and explanation of BSE technique significantly predicted frequency of BSE. Perceived risk, history of breast cancer, BSE demonstration, and a BSE handout did not affect BSE frequency. Of the five BSE teaching variables, only explanation of technique significantly predicted BSE satisfaction. Clinicians can promote BSE frequency by helping women feel confident about their abilities to perform BSE. PMID- 2600687 TI - Intending to breastfeed and work. AB - Many women who return to the work force during the first year following the births of their infants plan to combine breastfeeding and work; yet little is known about the process of preparing for the transition from breastfeeding in the home to continuing to breastfeed while employed. A study was conducted to explore mothers' decision-making processes during this transition. Interviews were conducted with 61 urban Canadian mothers who intended to continue breastfeeding after returning to work. Participants revealed that, although they intended to continue breastfeeding, whether or not they actually did depended on many factors that were beyond their control. These mothers had to play it by ear. They made elaborate plans, as well as back-up plans, allowing for all possible eventualities. PMID- 2600688 TI - Women's expectations of the labor and delivery nurse. AB - Sixty-one, Lamaze-prepared, married multigravidae identified their expectations of the labor and delivery nurse in semistructured interviews conducted at 36 to 38 weeks' gestation. Findings indicate variations in the amount of involvement women expected from the nurses during labor and delivery: limited (n = 17), moderate (n = 22), or extensive (n = 22). Women varied in the amount of time they wanted nurses present, who they expected to make caregiving decisions, and whether or not they wanted nurses to assist them in managing labor and delivery. PMID- 2600689 TI - Moral distress: a labor and delivery nurse's experience. AB - Moral distress occurs when nurses make moral decisions they cannot implement. This article contains a true account of such a case. A nurse was present at the delivery of a premature infant who was allowed to expire without intervention. A moral distress equation is used as a framework for describing the nurse's experience and its effects on her and her patient care. PMID- 2600690 TI - Individualized prenatal nursing care of pregnant adolescents makes a difference. PMID- 2600691 TI - Mathematically directed single-cut osteotomy for correction of tibial malunion. AB - In 1986 and 1987, four patients with tibial malunion involving both angular and torsional misalignment underwent surgical correction by a single-cut technique based on a mathematical model of long bone deformity. The technique involved a single surgical cut, followed by rotation of the two fragments along the osteotomy plane. The orientation of the osteotomy is based on a computer-assisted design. The deformity is measured on radiographs, computed tomography, and clinical exam and is then plotted on graphs to find the osteotomy orientation. The deformity involved varus and extension in four cases, internal rotation in 2, and external rotation in two. The deformities ranged from 9 to 26 degrees. The cutting angle of the osteotomy ranged from 50 to 66 degrees as measured from the transverse plane. Actual lengthening of 1 cm and functional lengthening over 1.5 cm was obtained without the use of bone graft. As no wedge of bone was removed, all corrected bones were easily suited to rigid internal fixation across the cut surface. In all cases, the desired correction was obtained within measurable error, and union was obtained with minimal immobilization. There were no soft tissue or joint contractures, and no neurovascular complications. In one patient, who had had four prior surgical procedures on the involved limb, an infection developed 6 weeks postoperatively that required debridement and delayed primary closure. As the technique involves only one cut, no wedge of bone is removed, no shortening occurs, and the osteotomy is highly suitable for rigid internal fixation. The described technique is the first to integrate in a precise way the correction of torsion with the correction of angular deformity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600692 TI - Autologous marrow injection for delayed unions of the tibia: a preliminary report. AB - Over a 3-year period, we have treated 10 delayed unions of the tibia by using percutaneous marrow injection rather than standard operative bone grafting. Nine of the 10 fractures responded by forming callus in the area where the marrow was injected. This relatively simple technique avoided potential problems associated with operative grafting methods that have been standard for at least 50 years. Most importantly, it encourages early treatment of fractures when healing problems are anticipated or are becoming evident. PMID- 2600693 TI - Microbiologic flora contaminating open fractures: its significance in the choice of primary antibiotic agents and the likelihood of deep wound infection. AB - A clear understanding of the significance of wound contamination as well as knowledge of the microbial flora that could be expected are needed in order to administer a rational and effective antibiotic treatment for open fractures. We have conducted a prospective study of the contaminating microbial flora in 89 open fractures. In addition, two more cultures were taken of all wounds not primarily closed. Wound and fracture healing were followed in all patients. Most fractures were Gustilo grade II (58.4%) caused by work-related accidents. Wound cultures were positive in 83% of all fractures, and a total of 84 strains of bacteria were isolated. In 39.3% of cultures, various species of aerobic Gram negative rods (most commonly Pseudomaonas aeruginosa) were retrieved, followed by Staphylococcus epidermidis (34.5%) and Staphylococcus aureus (26.1%). Repeat cultures were mostly either negative (59.5%) or grew saprophytic organisms that were usually nonpathogenic (such as various species of saprophytic Bacillus bacteria). The only cases that developed deep wound infection were those where a repeat culture 1 day after debridement grew the same organisms as the initial organisms. We conclude that (a) most open fractures are already contaminated upon the patient's arrival at the emergency department, in many cases by potentially pathogenic staphylococci and Gram-negative organisms; (b) contaminating organisms are community acquired and, as such, are sensitive to most routine antibiotics; and (c) persistence of the same organisms in a repeat culture taken 1 day after debridement signifies technical failure of debridement and a subsequent very high risk of infection. Therefore, achieving adequate wound asepsis immediately following debridement is of the utmost importance. PMID- 2600694 TI - A technique for obtaining bone graft. AB - A technique is described for obtaining large amounts of morselized cancellous graft to fill significant bony defects. This method uses an acetabular reamer placed against the outer wall of the posterior pelvis. Advantages of this technique include the procurement of copious amounts of homogeneous cancellous bone graft, ease of performance, little postoperative pain, and minimal bleeding. This technique should not be performed in elderly or osteopenic patients. PMID- 2600696 TI - Anterior and posterior cervical spine fixation using titanium implants to facilitate magnetic resonance imaging evaluation. AB - Magnetic resonance (MR) imaging of the cervical spine is useful in the evaluation of both acute and chronic injuries to the spinal cord and meninges as well as in demonstration of mechanical impingement on the spinal canal and nerve roots. Anterior or posterior plate fixation of unstable cervical spine injuries has limited the postoperative use of MR imaging due to the extensive magnetic field distortion produced by the stainless steel implants commonly used in these procedures. We have compared titanium implants in a cadaver against stainless steel implants in two patients and show no significant MR artifacts produced in the spinal canal by titanium plates as opposed to extensive image distortion and obliteration by the steel plates. We recommend consideration of titanium (Ti6A14V) as a substitute for stainless steel in cervical spine fixation to preserve the option of subsequent examination by MR scanning. PMID- 2600695 TI - Cancellous bone donor site regeneration. AB - Patients requiring cancellous bone grafting of an extensive deficit or multiple grafting procedures often lack a sufficient quantity of autogenous cancellous donor bone. This study was designed to determine the potential for reharvesting autogenous cancellous bone donor sites in a canine model. Fixed-sized cancellous bone grafts were harvested from the ilium of 12 mature, conditioned dogs. Ilia containing the donor sites were removed from groups of 3 dogs at intervals of 6 weeks, 3 months, 6 months, and 1 year. The donor sites were evaluated by roentgenograms, histology, and histomorphometric analysis and were compared to the opposite, nonoperated ilia, which served as controls. The analysis revealed a gradual replacement of the surgical defect with new cancellous bone by 1 year. Donor site reharvesting is a potential alternative to multiple site grafting or the use of allograft material. PMID- 2600697 TI - A modified pins-and-plaster technique incorporating early motion for fractures of the distal radius. AB - A modified pins and plaster technique allowing early wrist motion for comminuted intraarticular fractures of the distal radius was used in 14 patients. At an average of 12 days after injury, hinges were applied and the cast sectioned at the wrist. Wrist motion, controlled by the amount and site of cast removal, was allowed thereafter. This relatively simple method appeared to maintain a satisfactory fracture reduction and be advantageous in avoiding wrist stiffness. Careful attention to detail regarding pin placement is recommended. PMID- 2600698 TI - Occult scaphoid fracture: a diagnostic enigma. AB - In a prospective study, 38 patients with so-called "wrist sprains" and a clinical nonradiological diagnosis of scaphoid fracture were immobilized in a plaster cast for 2 weeks. At 2 weeks, six patients were found to have a complete fracture of the scaphoid through the waist. In view of this high incidence (15.8%) of occult scaphoid fracture, it is once again suggested that all cases of wrist sprains where scaphoid fracture is suspected be immobilized for a 2-week period. PMID- 2600699 TI - Component motion in bipolar cemented hemiarthroplasty. AB - A total of 17 patients with a cemented bipolar Hastings hemiarthroplasty were examined clinically and radiologically between 1 and 3 years after being treated for a displaced femoral neck fracture. Only a minor part of the motion in the Hastings prostheses took place between the metal femoral head and the polyethylene liner (intraprosthetic). In seven cases, no "true" intraprosthetic motion weightbearing was observed (including five cases with intraprosthetic motion caused by impingement). The relative amount of intraprosthetic motion did not decrease with weightbearing. The functional result was not correlated to the relative amount of intraprosthetic motion with weightbearing. In conclusion, the short-term success of the bipolar prostheses is probably not accomplished by a reduction in extraprosthetic motion caused by the biarticular design but by other factors, including the optimal indications for hemiarthroplasty (high age, low activity level), the consistent use of acrylic bone cement, and the shock absorbing effect of the polyethylene liner. PMID- 2600700 TI - Femoral fractures in Paget's disease. AB - Since the original description of osteitis deformans, the treatment of femoral fractures occurring in this disease process has been difficult. A retrospective study of 35 fractures treated over an 8-year period was undertaken to identify the factors that influenced the results. The fractures were classified according to four fracture patterns: subcapital, intertrochanteric, subtrochanteric, and shaft. Chart and radiographic analyses were then performed. The results identified subtrochanteric fractures, occurring in a somewhat younger population, to be the problem fracture. The other three fracture groups did well with standard methods of treatment. Uncemented arthroplasties were not successful; this correlates with the known bone physiology of this age group and this disease process. Blood loss was not statistically significant in any group, although it was greater in the subtrochanteric population. Preoperative assessment by bone scanning and preoperative medical treatment is recommended in the subtrochanteric fracture group. PMID- 2600701 TI - The effect of radial preload on the implant-bone interface: a cadaveric study. AB - The most common complication of external fixation is pin loosening. Preloading the implant-bone interface is believed to retard this process. Radial preload, in particular, may be useful, as it allows loading in more than one direction. To investigate the effect of varying degrees of radial preload on the pin-bone interface, 30 freshly thawed human cadaveric tibiae were sectioned into 4-cm segments. Uniform drill holes were produced in the anterior tibial ridge of all segments and custom experimental bolts, oversized in diameter by as much as 1 mm, were pressed into each specimen. Macroscopic surface fractures were noted at the time of bolt insertion for misfits greater than 0.2 mm. Following histologic preparation, the implant-bone interface was evaluated microscopically based on the appearance of osteonal compression, lamellar distortion, and microfractures. Insertion of external fixator pins with misfits of greater than 0.4 mm resulted in significant microscopic structural damage to the bone surrounding the pin. High degrees of radial preload, exceeding the elastic limit of cortical bone, may be produced around pin holes by a small misfit. The use of oversized pins or screws must therefore be questioned. PMID- 2600702 TI - A custom-made prosthesis for the treatment of supracondylar femoral fractures after total knee arthroplasty: report of four cases. AB - Four supracondylar femoral fractures following total knee arthroplasty, two because of intraoperative notching of the anterior femoral cortex and two because of osteoporosis, were revised using a custom-made prosthesis with femoral condyle section. At 1-6 year follow-up (median 3 years) after the revision, all patients had an excellent clinical result, although 2 had a prolonged rehabilitation period because of severe osteoporosis. At roentgenographic examination, no signs of loosening of the prostheses at the cement-bone interface were present. PMID- 2600703 TI - The stiffness of cylindrical casts enforced with splint laminations: biomechanical considerations. AB - Splint lamination is often used to strengthen a plaster cast while minimizing its thickness and weight. We evaluated the following lamination configurations to determine the effectiveness of each relative to a 3-mm-thick short leg cast: anterior-posterior splints, medial-lateral splints, and an anteriorly placed fin. Theoretical stiffness was calculated as a function of the area moment of inertia, and then the actual casts were tested in three-point bending on a servohydraulic apparatus. The experimental results were correlated with the calculated data, and finite element studies were performed to correlate the experimental results with the geometries of the casts. The theoretical and experimental data indicate that anterior-posterior splint lamination reinforcement stiffens a cylindrical cast to flexion-extension bending moments more effectively than does medial-lateral splint placement. An anterior fin can stiffen the cast as effectively as a splint can. However, the fin must be relatively large, which may cause it to accentuate problems with clothing and be difficult to apply. PMID- 2600704 TI - Prognostic indicators in tibial shaft fractures: serum creatinine kinase activity. AB - Serum creatinine phosphokinase (CPK) levels were measured serially in 50 adults with closed tibial shaft fractures. CPK activity increased significantly after fracture (p less than 0.001). High energy and slowly healing fractures had significantly higher levels than low energy and normally healing fractures, respectively. Thus, CPK determinations could be used to assess the severity of trauma and possibly prognosis in tibial shaft fractures. PMID- 2600705 TI - False-positive diagnosis of an odontoid fracture by CT scan. AB - Although computed tomography (CT) is a valuable tool for evaluating spine trauma, it's usefulness is limited. Horizontally oriented fractures of the cervical spine, particularly type 2 fractures at the base of the odontoid process, may be difficult to detect with CT. Our case report illustrates a false-positive diagnosis of this fracture and suggests that conventional polytomography is superior to CT for demonstrating this particular lesion when minimal displacement is present. PMID- 2600706 TI - Concomitant medial condyle fracture of the humerus in a childhood posterolateral dislocation of the elbow. AB - Fracture of the medial condyle of the humerus concomitant with a dislocation of the elbow is an extremely rare event in children. In this case of a 10-year-old boy, the fracture of the medial condyle was not diagnosed initially, which resulted in subsequent restriction of elbow range of motion. In such a case, it is suggested that one look for other injuries associated with elbow dislocations in children and undertake appropriate radiographic studies. PMID- 2600707 TI - Ipsilateral sternoclavicular dislocation and clavicle fracture. AB - A case of ipsilateral distal clavicle fracture and sternoclavicular joint dislocation is reported. This combination of injuries results from two separate forces in sequence. Closed reduction of the dislocation was possible only after open reduction and internal fixation of the clavicle fracture was performed, because of the inability to manipulate the free-floating segment. Patients should be carefully examined for associated brachial plexus injuries. PMID- 2600708 TI - Bilateral posterior hip dislocations with femoral head fractures. AB - An unusual case of bilateral posterior fracture-dislocation of the hip (Pipkin Type IV) occurred in a 63-year-old man with Paget's disease of the pelvis. Other injuries included a displaced humeral shaft fracture and patellar ligament disruption. Bilateral cemented total hip arthroplasty was performed to avoid the need for prolonged immobilization. Postoperative low-dose irradiation was used because of the risk of heterotopic ossification. PMID- 2600709 TI - Mechanical comparison of anterior spinal instrumentation in a burst fracture model. PMID- 2600711 TI - A mechanistic study of the electrochemical corrosion of the gamma 2 phase in dental amalgams. I. Evaluation of the measurements. AB - Conventional dental amalgams are prone to corrosion of the gamma 2 phase. In an anodic polarization experiment the presence of gamma 2 causes a current peak in the proximity of -250mV vs. SCE. Electrochemical impedance measurements carried out at this potential indicate the occurrence of an impedance curve in two parts. The high frequency part is a semi-circle with its centre below the real axis. Apart from the faradaic impedance and the double layer capacitance, the high frequency part is dominated by the behaviour of the corrosion products layer on the amalgam surface. The low frequency part has the form of a diffusion-like curve. However, since the phase angle is smaller for the above-mentioned case than for a free diffusion, this phenomenon is ascribed to diffusion in a porous layer at the interface between amalgam solution. PMID- 2600710 TI - Human bite force discrimination using specific maxillary and mandibular teeth. AB - The purpose of this study was to determine whether performance differences existed in subjects' self-generated bite force discrimination ability using maxillary and mandibular central incisors, canines, premolars and first molars. Two separate studies were conducted: (i) to assess whether performance differences existed in subjects' bite force discrimination ability using central incisors and premolars; (ii) to compare subjects' performance on bite force discrimination using central incisors, canines and first molars. Assessment of bite force was measured using a specially designed strain gauge scale allowing subjects to visually monitor when their biting force equalled a preset resistance. Resistance forces of 500, 1000 and 3000 g were selected as standards. Subjects were presented with a series of paired resistance settings, one at a time, the first of each pair being the standard and the second being the comparator setting of a predetermined amount. This paired-comparisons procedure was continued until the subjects' difference limen (DL) value (the threshold of discrimination between two forces) could be established. The first study revealed no significant (P greater than 0.05) overall difference in subjects' bite force discrimination ability relative to specific teeth. In contrast, in the second study a significant difference (P less than 0.05) was identified in subjects' performance relative to specific teeth; subjects' performed better using central incisors compared to first molars. In both studies, subjects' performance was significantly better (P less than 0.05) using the 500 g standard compared to the 3000 g standard in the first study, and compared to the 1000 g standard in the second study. No significant differences (P greater than 0.05) were observed between the performance of males and females in either study. PMID- 2600712 TI - A mechanistic study of the electrochemical corrosion of the gamma 2 phase in dental amalgams. II. Introduction of a model. AB - Electrochemical impedance measurements on conventional dental amalgams at an anodic polarization potential of -250 mV vs. SCE were performed. An initial evaluation was given in part I of this study; in the second part the results are interpreted in terms of a model. The latter, characterized by an equivalent circuit, is a parallel combination of a flat surface and a pore. The selection of appropriate values for the elements of the equivalent circuit leads to a better insight into the corrosion process. Although no simple relationship exists between the circuit elements and the impedance curves, an explanation was found for some typical features of these curves. As an application, the influence of the anodic polarization potential on the impedance curves was studied. Evaluation by means of the model demonstrated the importance of the characteristics of the corrosion products. PMID- 2600713 TI - Comments on standardization of reflex measurements in human masseter muscle, including silent periods. AB - The following comments are given on the guidelines suggested by Turker (1988) for studies on oral reflexes using the surface EMG of the masseter muscles in man, including the silent period. (i) Attention should not be confined to electrical stimulation since mechanoreceptors in the periodontium, especially in the periodontal ligament, can only be activated by mechanical stimulation of a tooth. Furthermore, different modes of stimulation and stimulation sites do not yield equivalent reflex complexes. Weak and transient mechanical stimulation of a tooth while clenching at a low level of 5 or 10% MVC is a selective model (89%) to study the influence of periodontal receptors. (ii) Statistical criteria should be applied on rectified and averaged EMG records to prevent any subjective bias in the measurements of reflex variables. Whether a period of increased EMG activity is due to clustering of action potentials of motor units firing of which was delayed by a preceding inhibition, or to a real excitatory influence, can be assessed by applying statistical criteria on averaged and subsequently rectified records. (iii) The clenching level should be less than 25% of MVC to avoid muscle fatigue, and to elicit pronounced reflexes with a weak and therefore more selective stimulus. (iv) The stimulus intensity should be much less than six times the threshold if selectivity for mechanoreceptors is desired. Furthermore, periods of increased activity in surface EMG resulting from a weak stimulus are probably due to real excitatory influences and not to clustering of motor unit action potentials after an inhibition. (v) Jaw separation and the use of a force transducer are not always advantageous. If mechanical stimulation is applied to a tooth, clenching in full habitual occlusion causes a complete suppression of the influence of muscle spindles. A shift in activity between the various elevator muscles, and hence a change in activity of the muscle studied, may occur during an experimental session if biting force is used as a feedback. Such a shift is not relevant if feedback is carried out on rectified and low-pass filtered (1.6 Hz) EMG of the muscle studied. PMID- 2600714 TI - Effect of mucin on the corrosion behaviour of dental casting alloys. AB - The influence of mucin on the corrosion behaviour of seven typical dental casting alloys was investigated. A commercial saliva substitute (Saliva Orthana) containing mucin, and a control from which the mucin had been removed, were used. The electrochemical behaviour of the test alloys was evaluated around the open circuit potential (OCP) utilizing standard potentiodynamic techniques, as a function of oxygen concentrations and pH. The results of the corrosion measurements were analysed by a four-way ANOVA to detect the influence of alloy, environment and possible interactions. Mucin seems to act as a cathodic inhibitor at pH 6.7 but not at pH 4.6. An unidentified component (e.g. benzoate) of the saliva substitute probably acts as an adsorption inhibitor. Anodic passivation is also correlated with the artificial saliva composition. PMID- 2600715 TI - In vitro acid decalcification of human surface enamel pretreated with toothpaste slurries. AB - An in vitro caries-like challenge of human tooth enamel treated with inorganic fluoride (NaF) and organic fluoride (aliphatic and aromatic amine fluorides) toothpaste slurries has been investigated. The results revealed that the organic fluoride-containing toothpastes affected positively the resistance of tooth enamel to demineralization. PMID- 2600717 TI - Supplemental anesthetic techniques. PMID- 2600716 TI - Understanding profit. PMID- 2600718 TI - A position paper: human immunodeficiency virus and hepatitis B virus. PMID- 2600719 TI - ASHP clarification. PMID- 2600720 TI - Reader researching state laws on P.I.C.C.'s. PMID- 2600721 TI - Management of malpositioned central venous catheters. AB - Through research and clinical trials at The University of Texas M. D. Anderson Cancer Center, central venous catheters have gained wide acceptance and are being used for an increasing number of applications. More than 30,000 patients have had a CVC placed since the inception of the M. D. Anderson program in 1976. The soft and less thrombogenic silicone elastomer catheter is the most commonly used catheter in the institution. This study found that most commonly observed malpositions are related to the puncture site and technique, venous anatomy, and catheter characteristics. The study also indicated that the majority of malpositioned central venous catheters need not be removed but can be safely repositioned using rapid flushing, patient positioning, partial withdrawal, or simple or deflective guidewire techniques. Early recognition and management of malpositioned central venous catheters not only guard against serious complications but also allow proper catheter function and prevent delay of intravenous therapy. PMID- 2600722 TI - Intraosseous infusion: a lifesaving technique that should be used more widely. PMID- 2600723 TI - Continuous ambulatory gamma globulin infusion in the home setting: a treatment proposal for a high-risk patient. AB - As infusion therapies increasingly move from the hospital to the home setting, home I.V. therapy nurses must frequently decide which therapies are appropriate for home delivery. These practitioners must find innovative, cost-effective, and, most important, safe methods of providing new I.V. therapies in the home. A medically complex patient with a strong desire to maintain the most normal lifestyle possible was introduced to our infusion team. We accomplished our goal- to institute and maintain home therapy on this patient--by designing a treatment proposal that outlined specific guidelines, criteria, and recommendations for all aspects of the infusion care. This proposal can serve as a model for any experimental or unusual treatment being considered for home therapy. PMID- 2600724 TI - Protecting the intravenous nurse from blood-borne pathogens. AB - Intravenous nurses are at risk for infection with blood-borne pathogens to the extent that they are directly exposed to blood. By classifying work-related tasks according to potential for exposure and by implementing appropriate precautions for each task, the I.V. nurse's risk of infection can be minimized. PMID- 2600725 TI - The i.v. nurse and the i.v. drug abuser: medical and psychosocial implications. AB - When I.V. nurses treat I.V. drug abusers, they must be aware of the medical and psychosocial issues relevant to this group. Medical issues include the I.V. drug abuser's depleted venous access and this group's high rate of infection with HIV and other blood pathogens. Psychosocial issues relate to the various social and psychological problems associated with drug abuse. Further, when caring for these patients who are at high risk for HIV and other serious blood infections, the I.V. nurse may experience a conflict between her desire to care for the patient and her fear of contracting HIV or another infection through patient contact. Education is recommended so that I.V. nurses can reduce their risk of infection with blood-borne diseases and can better understand these patients. Also suggested are a multidisciplinary approach to treatment and referral to drug rehabilitation programs. PMID- 2600726 TI - Justice Department investigation of price-fixing. PMID- 2600727 TI - Peer review. PMID- 2600728 TI - Parenterals and pharmacy education. PMID- 2600729 TI - Review of biosafety guidelines. Biosafety Task Force, Parenteral Drug Association. AB - The increased use of recombinant DNA technology, human cell lines, and other human-source materials in the production of pharmaceutical products, has brought to the fore concern for the protection of our employees. A number of guidelines are available that cover "biosafety" issues and are reviewed in this article. PMID- 2600730 TI - Photostabilization of doxorubicin hydrochloride with radioprotective and photoprotective agents: potential mechanism for enhancing chemotherapy during radiotherapy. AB - p-Aminobenzoic acid (PABA), urocanic acid, and sodium urate were found to significantly enhance the photostability of doxorubicin hydrochloride [adriamycin, (ADR)]. d1-Methionine, thiourea, and glycine also increased the photostability of this drug, but to a lesser degree. Sodium thiosulfate on the other hand, was found to be detrimental to the photostability of ADR. The photostabilizing effect of PABA was found to increase with increase of its concentration and was influenced by the pH and the buffer species of the vehicle. The findings would have an impact on the enhancement of therapeutic efficacy of adriamycin when administered during radiation therapy. PMID- 2600731 TI - Development of a non-surfactant formulation for alfaxalone through the use of chemically-modified cyclodextrins. AB - The poor water solubility of alfaxalone (less than 5 micrograms/mL), a useful steroid anesthetic agent, was dramatically increased via complexation with a series of four cyclodextrins. The most effective agent was 2-hydroxypropyl-beta cyclodextrin (2HPCD) which solubilized alfaxalone in a linear manner as a function of concentration. At a 2HPCD concentration of 50% w/v, approximately 80 mg/mL of alfaxalone was dissolved indicating an increase in aqueous solubility of over four orders of magnitude. The cyclodextrin solution was stable to autoclaving and could be conveniently lyophilized to yield a solid product. PMID- 2600732 TI - Preclinical development and characterization of an intravenous dosage form for the ACE inhibitor RS-10029. AB - Preclinical development of an intravenous dosage form for the ACE inhibitor RS 10029 involved the formulation and characterization of the drug's chemical/physical stability in two prototype formulations (injectable solution and lyophilized powder). Included in these studies were quantitative evaluations of various processing and administration parameters (membrane qualification, terminal sterilization, compatibility/delivery of the drug with typical infusion fluids and administration sets) on finished product integrity and quality. Analytical methodology used in these studies consisted primarily of a stability specific HPLC assay and a light obscuration based sensor (HIAC) for particulate matter analysis. Results of these studies indicate that the drug is relatively stable at ambient temperature and under accelerated storage conditions (predicted T90 at 25 degrees C greater than 2 yr, and T90 at 50 degrees C greater than 2 mo). However, the ability of the product to withstand a full terminal sterilization cycle is limited, and therefore other approaches toward sterile processing were examined. With regard to the stability and compatibility of the drug in a variety of fluids and devices there appears to be no overt limitations in its use for either bolus or infusion delivery. PMID- 2600733 TI - Recovery of endotoxin preparations from the surface of glass capillary tubes. AB - The gel-clot method of the Limulus Amebocyte Lysate (LAL) test was used to determine the recovery efficiency of four different endotoxin preparations from Type I glass capillary tubes. Each capillary tube was charged with 10,000 endotoxin units (EU) and vacuum-dried at 50 degrees C. Average recovery for the Whittaker M.A. Bioproducts Control Standard Endotoxin (CSE), which contained fillers, was 90% (80-100%), for the Difco Laboratories and Associates of Cape Cod endotoxins 47% (40-80% and 20-100%, respectively), and for the rough lipopolysaccharide 70% (40-100%). The presence of fillers appears to increase the percentage of endotoxin recovered and decrease the inconsistency in recovery results. The overall recovery rates for the pure endotoxin formulations were higher and slightly more consistent than those reported in previous studies. PMID- 2600734 TI - Inulin disposition following intramuscular administration of an inulin/poloxamer gel matrix. AB - The disposition of inulin in rats was characterized following the administration of an i.v. solution, an i.m. solution, and an i.m. injectable gel (25% w/w poloxamer 407). Blood activity levels of tritiated inulin were followed over a 6 hour time period for all intravenous (i.v.) and intramuscular (i.m.) formulations. Following i.v. solution administration, a biexponential equation was required to characterize the disposition of inulin from the blood. The total blood clearance was approximately 1.5 mL/min/100 gm body weight. This value, when converted to plasma clearance, Clp/F, (0.807 +/- 0.100 mL/min/100 gm, n = 13), was within the range of values reported for the glomerular filtration rate (GFR) in rats (range 0.55 to 1.2 mL/min/100 gm body weight). The plasma clearance of inulin following administration of an i.m. solution (0.928 +/- 0.173 mL/min/100 gm, n = 9) was in close agreement to the value observed following administration of an i.v. solution. The plasma clearance of inulin following i.m. administration of the inulin/poloxamer gel formulation containing 25% w/w poloxamer 407, however, was markedly reduced (0.316 +/- 0.222 mL/min/100 gm, n = 8). A similar reduction in the value of the plasma clearance (0.309 +/- 0.017 mL/min/100 gm, n = 5) was observed following administration of an inulin solution to rats which had previously (1 hour) been injected i.m. with poloxamer 407 vehicle only (25% w/w). Thus, based on this preliminary study, it appears that simultaneous administration of inulin with poloxamer 407 as a gel formulation results in an alteration of the rat kidney to efficiently clear inulin by means of glomerular filtration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600736 TI - Tinea capitis caused by Microsporum praecox in a patient with sickle cell anaemia. AB - Microsporum praecox Rivalier ex Padhye, Ajello et McGinnis is the validated name for the taxon originally published as Sabouraudites praecox Rivalier. We describe here the first case of small-conidial, ectothrix type hair invasion caused by M. praecox in an adult woman from Oklahoma, U.S.A., suffering from sickle cell anaemia. This fungus is now being encountered with greater frequency as an etiologic agent of ringworm infection. PMID- 2600735 TI - Aztreonam for injection (lyophilized): development of an automated solution batching process utilizing volumetric powder feeders. AB - As part of a commitment to fully automate the manufacture of a lyophilized dosage form of Azactam (Aztreonam for Injection), an automated solution batching procedure was developed. The lyophilization process requires solution batching of Aztreonam and L-arginine, the two constituents of the product. To avoid preblending of aztreonam and L-arginine prior to dissolution, a batching process was developed which makes use of two separate volumetric powder feeders. In conjunction with a feedback pH control system, these powder feeders provided for (a) a faster batching process, (b) a tight control of solution pH during batching, (c) a failsafe system to prevent operator error and equipment malfunction. Data are presented correlating bulk densities of various powders with feeder output along with solution pH profiles determined using the manual mode and the automated feedback pH control system. PMID- 2600737 TI - Mel- mutants of Wangiella dermatitidis in mice: evaluation of multiple mouse and fungal strains. AB - Melanin-deficient mutants of Wangiella dermatitidis were studied by comparing a spontaneous mutant (Mel 3) with the parental wild type (wt) in four strains of mice and by comparing various UV-induced mutants in a single strain of mouse. Mice were inoculated intravenously with 3 x 10(6), 1 x 10(7), 3 x 10(7) or 1 x 10(8) yeast-like cells and mortality assessed at the end of 20 days. Neuropathology was evaluated in methenamine-silver stained brain sections of the different strains of mice injected with either wt or Mel 3 (1 x 10(7) cells per mouse). In general, both fungus strain related and mouse strain related differences in mortality were observed. The DBA/2J mouse was the most susceptible to fatal infection with all fungus strains. In the other strains of mice, however, the melanin deficient mutants were significantly less virulent than the wt at a concentration of less than or equal to 3 x 10(7) cells per mouse. No obvious trend was seen in the numbers of brain lesions in different strains of mice with respect to wt vs. Mel 3. However, invasive hyphal forms did seem to be associated with virulence. PMID- 2600738 TI - Freeze-dried bone in pulpotomy procedures in monkey. AB - The purpose of this study was to evaluate the effect of freeze-dried bone on amputated pulps. Fifteen primary and one permanent monkey teeth were treated with freeze-dried bone. As the control group, another fifteen primary teeth were treated with calcium hydroxide and fifteen primary and one permanent teeth with formocresol. Four other primary teeth pulps were amputated and sealed with tin foil and IRM as controls. Twelve mandibular incisors were left intact. Histologically all but three teeth treated with human freeze-dried bone after three months showed a complete or partial calcific barrier directly below the amputation site. Normal appearing odontoblastic cells were noted below the calcific barrier. The apical third was vital with an occasional chronic inflammatory cell visible. The histological findings of teeth treated with calcium-hydroxide were very similar to freeze-dried bone. All but four teeth showed a complete calcific barrier at the amputation site. The odontoblastic cells were normal in appearance and the inflammatory cell reactions decreased from the middle portion toward the apical region. The histological evaluation of the formocresol-treated teeth was comparable with previously published studies. PMID- 2600739 TI - Airway obstruction, palatal vault formation and malocclusion: a cross-sectional study. AB - A cross-sectional study of one thousand and sixty-five children (508 boys and 557 girls) from the Watertown School System was done in order to determine whether there is a relationship between airway obstruction, palatal vault formation and malocclusion. The age range was 5 to 12 years old with a mean age of 8.5 years. Breathing pattern was based on the lip competency (seal) of each individual. The height of the palatal vault, the Angle's molar classification, cuspid relationship, the anterior and posterior cross-bites, the deep-bites or open bites were also recorded. Enlarged tonsils were observed and the presence of allergies was noted. High palatal vaults were observed in children with lip incompetency (85.8%), and in children with Class II (73.6%) and Class III (65.3%). Anterior and/or posterior cross-bites accompanied high palatal vaults. From the examined children in this study, 20% presented known allergies. Eighty (80%) percent of the allergic children had high palatal vaults. Enlarged tonsils were also found in children with high palatal vaults. PMID- 2600740 TI - Fluoride levels in mother's milk. AB - The level of fluoride in milk samples of a group of Malaysian mothers residing in a fluoridated area (0.7 ppm) was analyzed using a fluoride electrode. All the mothers were residents in the locality for at least a year and they were screened for drugs and fluoride supplements. The concentration of fluoride in the milk samples ranged from 0.024-0.172 ppm. The mean value was 0.077 ppm. There were some variations in the fluoride levels of milk samples collected on two separate occasions from the same mother. The implications of these findings on fully breast-fed infants were discussed. PMID- 2600741 TI - Size and development of the dentition in endocrine deficiency. AB - Two case reports are presented of boys, who were found to have pituitary and thyroid dysfunction respectively. This was treated in childhood with replacement therapy. These deficiences are known to affect normal skeletal and dental development, but the cases described also showed marked effects on the dental tissues themselves with severe microdontia and abnormalities of crown and root form. PMID- 2600742 TI - Oral and dental anomalies in Goltz syndrome. PMID- 2600743 TI - The pedodontist's tool box: Part 2 anchors for success. PMID- 2600744 TI - Pulp: Part 1. Nerves and nerve endings. PMID- 2600745 TI - Pulp: Part 2. Blood vessels and lymphatics. PMID- 2600746 TI - Occurrence of gingival recession in adults. AB - The occurrence of gingival recession was investigated in adults by age and gender and in relation to their dental status and frequency of toothbrushing. A total of 258 dentate subjects were clinically examined. Their mean age was 46 years and they had an average of 19.4 natural teeth. Gingival recession was recorded as present if any root surface was clearly visible without retraction of the gingival tissue. Recession was found on at least one tooth surface in 68% of subjects. Mean number of surfaces with recession was 7.2 for women and 10.4 for men. Subjects with gingival recession had fewer natural teeth than did those without recession. The two groups did not differ from each other in the number of filled teeth and decayed teeth. Mandibular teeth had more surfaces with recession than did maxillary ones. Sites of recession occurred quite symmetrically. Frequent toothbrushers had, both in the maxilla and mandible, more surfaces with recession than had those brushing their teeth infrequently. Frequent toothbrushing had a greater association with recession among women and in the youngest age group. PMID- 2600747 TI - Prevalence of periodontal breakdown in adolescents and presence of Actinobacillus actinomycetemcomitans in subjects with attachment loss. AB - The present investigation was carried out to study the prevalence and clinical appearance of destructive periodontal disease in a school population of 15- to 16 year old adolescents in Amsterdam. In addition the prevalence of Actinobacillus actinomycetemcomitans was studied in those subjects showing attachment loss. Attachment loss was diagnosed in 230 of the 4565 subjects participating which is about 5% of the population studied. Within this population males were more frequently affected than females (P = 0.008). Extensive periodontal destruction was found in 16 subjects (0.3%). In this group a female/male ratio was found of 1.3:1. As a result of the epidemiological survey, 105 subjects with attachment loss volunteered for further investigation. The results showed that presence of plaque, redness and swelling of the gingiva, and bleeding on probing were general phenomena. In addition, the bleeding/plaque ratio, as determined for each subject at sites without attachment loss, increased with the severity of periodontal disease as expressed by the number of sites with attachment loss (P = 0.0038) as well as by the amount of destruction at these sites (P = 0.002). A. actinomycetemcomitans could be identified in 18 of the 105 subjects with attachment loss. Analysis showed that A. actinomycetemcomitans was more frequently isolated in subjects with moderate to severe periodontal breakdown than in subjects with mild breakdown (P less than 0.02). When estimating the percentage of juvenile periodontitis patients on the basis of the classically accepted criteria, it seems likely that between 0.1% to 0.2% of the population in Amsterdam is suffering from this disease entity. PMID- 2600748 TI - Human freeze-dried dura mater allografts as a periodontal biological bandage. AB - Freeze-dried dura mater allografts (FDDMA) were used as a biologic bandage covering periodontal osseous defects which were grafted with autogenous bone particles. Seven consenting adult patients having multiple one-, two-, and wide three-wall periodontal osseous defects participated in the study. Four to 6 weeks following initial preparation, all defects were treated by full thickness flap surgery, debridement of defects, root planing, intramarrow penetration as needed, and autogenous bone grafts that filled the defects. Randomly selected grafted defects in each patient were then covered with FDDMA (experimental) or by the host flap (RF) (control). Periodontal dressing and systemic tetracycline (250 mg q.i.d.) were used for 7 days. Frequent maintenance was performed until reevaluation at 6 months postsurgically. Soft tissue results showed no significant differences in initial probing pocket depths, recession, or gain of probing attachment. There was a significantly greater amount of probing pocket depth reduction and significantly shallower residual pockets when FDDMA was used. Hard tissue findings indicated that there were no significant differences in initial defect depth, amount of crestal resorption, or amount or percent of defect fill with either treatment. There were significant differences in the percent of defect resolution and the depth of the residual defect in favor of the FDDMA treatment. None of the FDDMA sites were felt to need a secondary surgery to correct residual defects or residual pockets. This study suggests that FDDMA may be beneficial as a "biologic bandage" to cover periodontal osseous defects that were filled with autogenous bone grafts. The trends in this study suggest that FDDMA may be very useful in periodontal regeneration procedures. PMID- 2600749 TI - Caries on root surfaces exposed following gingivectomy in conventional rats infected with Streptococcus sobrinus and Actinomyces viscosus. AB - To study the ability of bacteria associated with coronal caries to initiate root surface caries, a rat model was used. Root surfaces were exposed by gingivectomy in rats fed a caries-promoting diet and orally inoculated with either Actinomyces viscosus M-100, Streptococcus sobrinus (mutans) 6715, or both. A fourth group received a diet containing antibiotics. The animals were sacrificed 64 days following the gingivectomy performed on the right molar quadrants. Gingivectomy significantly increased exposed lingual root length and root caries incidence. There were no caries on non-gingivectomy root surfaces. Root surface caries incidence in the groups inoculated with A. viscosus and A. viscosus plus S. sobrinus did not differ. For both these groups, root caries incidence was significantly greater than that for the group inoculated with S. sobrinus alone. Root caries incidence in this latter group did not differ from that in the control group. PMID- 2600750 TI - Computer-based thermal imaging of human gingiva: preliminary investigation. AB - Computer-based thermal imaging techniques were used to compare the rewarming rates of normal and inflamed human gingiva following cooling. A Modified Gingival Index (MGI) score, gingival crevicular fluid (GCF) measurement, and clinical photograph were obtained from a maxillary or mandibular anterior facial region in 20 subjects, aged 25 to 44. Baseline thermograms of the marginal/papillary (M/P) and adjacent attached gingiva (AG) were recorded following an acclimatization period with the patient seated and chin resting on a positioning apparatus. The tissue was then cooled with a gentle stream of air and thermograms were recorded at 10 second intervals for 3 minutes as the tissue rewarmed. Rewarming slopes were calculated based on these thermograms. Correlation coefficients were calculated for MGI with GCF, as well as for both MGI and GCF with AG and M/P rewarming slopes. Mean baseline (SE) temperatures (degrees F) for AG were 75.9 (0.9), 78.0 (0.6), and 80.3 (1.3) for normal, mildly inflamed, and moderately severely inflamed gingivae, respectively; corresponding mean (SE) temperature differences (degrees F) between AG and M/P were 0.5 (0.2), 0.9 (0.2), and 1.4 (0.3). Intragroup mean M/P temperatures were less than mean AG temperatures, with the mean regional differences increasing with greater severity of inflammation. Rewarming rates also increased as inflammation became more severe, with the rewarming slopes of both the AG and M/P having statistically significant correlations with the MGI and the GCF. The correlation between MGI and GCF was also statistically significant. This study suggests that computer-based thermal imaging techniques can detect both static and dynamic temperature differences between normal gingiva and gingivae with increasing severities of inflammation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600751 TI - The glycosylated hemoglobin assay for diabetes: its value to the periodontist. Two case reports. AB - The glycosylated hemoglobin assay is a relatively new test used in the diagnosis and monitoring of the diabetic patient. This assay should be of interest to the periodontist as it offers important advantages over traditional blood glucose testing methods. Most importantly, it gives an indication of the blood glucose level over an extended period of time (30 to 90 days), whereas traditional assays only indicate the glucose level at one point in time. Additionally, there is no requirement for fasting prior to testing. Two case reports are presented to illustrate how the glycosylated hemoglobin assay can be utilized by the periodontist. PMID- 2600752 TI - Effect of periodontal dressings on human gingiva fibroblasts in vitro. AB - In vitro cytotoxicity studies of periodontal dressings have not generally produced a result consistent with in vivo observations. These prior in vitro studies have not used human intraoral cell lines. We tested the effects of two eugenol containing and two non-eugenol periodontal dressings on cultured human gingival fibroblasts (HGF) (ATCC #1292). Replicate HGF cultures grown in microtiter plates were exposed to stock, 1:4 and 1:16 dilutions of extracts made from each of the four periodontal dressings. The HGF cultures were pulse labelled with tritiated thymidine (3HTdR) after 24, 48, and 72 hours. Incorporations of the labelled thymidine were measured using liquid scintillation counting and expressed as counts per minute. The results showed that undiluted extracts from all four periodontal dressings totally inhibited 3HTdR uptake (P less than 0.05). The 1:4 dilution of eugenol dressings inhibited 3HTdR uptake significantly more than non-eugenol dressings (P less than 0.05). Interestingly, at 72 hours the 1:16 dilution of the non-eugenol dressings caused significantly increased 3HTdR uptake which was not observed with the eugenol dressings. The present results suggest that the use of a human fibroblastic cell line for testing the effects of periodontal dressings may provide information about the relative biological effects of these dressings. Using this cell line, we have found that eugenol dressings inhibit fibroblast proliferation to a greater extent than non-eugenol dressings. PMID- 2600753 TI - Clinical and microbiological characteristics of treated periodontitis patients on maintenance care. AB - A population of 98 adults previously treated for moderate to advanced adult periodontitis and currently maintained in a recall program for at least one year were recruited for this study. The ultimate purpose of the study is to determine whether the presence of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis, and Bacteroides intermedius in selected periodontal sites can predict the future clinical course of these patients, particularly with respect to disease recurrence. This report presents the clinical design of the study which allows comparisons between sites positive and negative for these species in infected patients, and between sites in infected patients and comparable sites in non-infected patients. In addition, some base line clinical and microbiological data for these patients are presented. The distribution of PII and GI scores tended to be highest for molars, with the remaining teeth having similar scores. Probing depth measurements were greater for mesio-distal than oro-vestibular recordings. A bilaterally symmetrical pattern of increasing probing depth was noted from the midline distally on mesio-distal as well as oro-vestibular surfaces. Sites positive for the target organisms listed above tended to have greater probing depths (mean: 4.14 +/- 0.1 mm) than non-infected sites in the same patients (mean: 3.76 +/- 0.1 mm) or comparable sites in non-infected patients (mean: 3.54 +/- 0.1 mm). PMID- 2600754 TI - Effects of penicillin and erythromycin on the clinical parameters of the periodontium. AB - The clinical effects of systemic penicillin and erythromycin on the periodontium were investigated. There are only a few studies of the effects of these antibiotics on clinical periodontal parameters. Of the 72 subjects in the study, 24 belonged to the penicillin group, 21 to the erythromycin group and 27 to the control group. Plaque and gingival indices, tooth mobility, and probing depths of gingival pockets were recorded before the drug treatment. Radiographs were taken. Both antibiotics decreased plaque, and erythromycin also decreased gingivitis. In the penicillin group 10 of the 24 patients developed abscesses during the study, and the studied clinical parameters worsened. These patients had more severe periodontitis initially than the persons with no acute reaction. The clinical changes had returned to the baseline level by 12 weeks after the antibiotic treatments. There were no significant or lasting effects of antibiotic treatment alone in patients with overt periodontitis. PMID- 2600755 TI - The effectiveness of a counter-rotary action powered toothbrush and conventional toothbrush on plaque removal and gingival bleeding. A short term study. AB - Initial investigations have demonstrated the effectiveness of a new contra-rotary powered electric toothbrush in removing plaque supragingivally, subgingivally, and interproximally following a single use. The purpose of this study was to evaluate the effectiveness of a counter-rotary toothbrush following 1) one time instruction, 2) reinstruction and 1 week practice; and 3) a third instruction and 3 weeks of practice and home use. Twenty-four patients were studied; 12 using the counter-rotary toothbrush and 12 using a conventional toothbrush. Using O'Leary and Turesky plaque indices, both brushes significantly reduced supragingival plaque from baseline at all intervals. The counter-rotary brush, however, was more efficient than the conventional brush at all intervals (P less than 0.01). Using a Surface Area Plaque Index, both brushes significantly reduced supragingival plaque from baseline at all intervals but there were no significant differences between brushes. A timed bleeding index showed significant reduction in gingival bleeding following 28 days of brushing with both brushes. Again, the counter-rotary toothbrush was superior to the conventional toothbrush (P less than 0.01). PMID- 2600756 TI - The mouthrinse wars. PMID- 2600757 TI - Painting group portraits: studying life outcomes for aggressive and withdrawn children. AB - Aggression and social withdrawal have long been of interest to personality psychologists. The present article presents a longitudinal study of the development of children selected from a community sample who were high on aggression and withdrawal. The selection of outcome variables is discussed, and outcomes during adolescence are described. For both males and females, high aggressiveness was predictive of low intelligence, poor school achievement, and psychiatric problems. For females, high aggressiveness was also predictive of general health problems. High social withdrawal was predictive of poor school achievement. Females who were high on withdrawal also had an elevated rate of abortions. Individuals who were high on both aggression and withdrawal had relatively poor social competence, had general problems with behavior, had low intelligence, and were performing poorly in school. PMID- 2600758 TI - Membrane formations in the pineal cells of the teleost Gambusia affinis. AB - Highly organized membrane formations in the cytoplasm of photoreceptor and supporting cells of the pineal organ of Gambusia affinis are described. These membranous structures show different characteristics depending on the cell type where they are located. Some of the morphological characteristics of these membranous formations are similar to those of myeloid bodies, but their presence in the photoreceptor cells raises some doubt about their being myeloid bodies. The three-dimensional interpretation of these structures is discussed. PMID- 2600759 TI - Influence of serotonin and melatonin on some parameters of gastrointestinal activity. AB - In vitro melatonin (M) reduced the tone of gut muscles and counteracted the tonic effect of serotonin (5-HT). In vivo 0.1 to 4 mg of 5-HT (contained in beeswax implants) decreased the food transit time (FTT) in a dose-dependent manner, but higher doses (5 and 6 mg) increased the FTT. Melatonin injected intraperitoneally into mice bearing 5-HT implants (2 mg per animal) blocked partly the serotonin effect and increased FTT by 50%; however, no dose-dependent effect was observed when doses between 0.01 and 1 mg were used. Surprisingly, M injected into intact mice decreased FTT to levels comparable to those observed in 5-HT implanted, M treated mice. Again, this significant decrease was not dose-dependent between 0.02 and 1 mg. Although in vitro the maximal inhibition of serotonin-induced spasm was achieved when the M:5-HT ratio was 50-100:1, in vivo the effective ratio was about 1:1. This may indicate that part of M action on the gut movement is mediated by extraintestinal mechanisms. A hypothetical, counterbalancing system of M and 5-HT regulation of gut activity (similar to adrenaline acetylcholine system) is proposed. PMID- 2600760 TI - Effect of different nocturnal illuminances on melatonin, prolactin, and gonadotropins in male rats. AB - We studied the role of nocturnal illuminance as a possible regulatory factor in the production and secretion of reproductive hormones. Adult male rats were kept under artificial lighting conditions (LD 12/12 hours) where the daily illuminance was 520-550 lx and the nocturnal illuminance 0, less than 0.1, or 1-1.5 lx. After a 7 day adaptation period, the pineal contents of melatonin, the serum levels of LH, FSH, and prolactin, and the pituitary contents of these hormones were measured by radioimmunoassay in samples taken 4 and 7 hours after the onset of light and onset of darkness. When the rats were kept in full darkness or under the minimal nocturnal iluminance (less than 0.1 lx), the patterns of pineal melatonin were equal. When nocturnal illuminance was 1-1.5 lx, the pineal melatonin contents at night were lower than in complete darkness. However, this illuminance level did not totally abolish the nocturnal increase of melatonin synthesis. The serum levels of LH, FSH, and prolactin were all affected by the increase of nocturnal illuminance so that the difference between the daytime and nighttime levels increased (higher values during the night). The variation of nocturnal illuminance did not change the pituitary contents of gonadotropins. The effects on pituitary prolactin were negligible as well. The results are interpreted to support the concept that nocturnal illuminance levels may regulate the secretion of the studied hormones in male rats. PMID- 2600761 TI - Cerebrospinal fluid-contacting area of the deep pineal: effects of photoperiod. AB - The surface of the pineal recess of the Syrian hamster demonstrates three morphologically distinct zones that are classified as the peripheral, transitional, and central zones. The central zone is the most remarkable because of the number of distinguishable morphological specializations in this region that appear to indicate interaction between the cerebrospinal fluid (CSF) and associated ventricular structures and the deep pineal gland. CSF-contacting pinealocytes are present in the central zone and have a relatively indistinct ventricular surface except for the presence of surface blebs and pinealocyte processes that course on the surface of the deep pineal. Supraependymal neurons and neuronal processes appear to converge on the central zone, occasionally having presumptive terminals that are associated with the cells of the central zone. When the hamsters were maintained in a short photoperiod (LD 8:16), the CSF contacting area of the pineal recess was significantly larger in those hamsters killed 2 hours before lights off compared to those killed 2 hours before lights on (P less than 0.01). There were no significant differences in the CSF contacting area when comparing two groups of hamsters maintained in a long photoperiod (LD 14:10, killed 2 hours before lights on and lights off, respectively). There was statistically significant interaction (P less than 0.05) between the lighting cycle and the time of day of death on the appearance of CSF contacting pinealocytes. The hamsters maintained in LD 8:16 had significantly reduced testicular weights when compared to those maintained in LD 14:10. The plasticity of the central zone and the associated CSF-contacting pinealocytes of the pineal recess of the hamster are evidence that this region demonstrates morphological changes that are dependent upon the physiological state of the animal. PMID- 2600762 TI - Effects of melatonin on the growth of MtT/F4 anterior pituitary tumor: evidence for inhibition of tumor growth dependent upon the time of administration. AB - In the present report, we have examined the anti-tumor potential of melatonin by utilizing the MtT/F4 anterior pituitary transplantable tumor. The tumor was obtained (Bogden Labs.) in cryopreserved condition and transplanted (in the left rear thigh), and allowed to grow for 8 weeks in adult Fischer 344 rats, maintained under uniform laboratory conditions of light (LD 14:10; lights on at 06:00 h), and temperature (21-23 degrees C). Subsequently, the tumor was dissected out, minced, and washed in Medium 199, and similarly transplanted into groups of adult Fischer 344 rats representing the final tumor recipient groups utilized for the evaluation of melatonin's anti-tumor effects. Melatonin (50 micrograms/0.1 ml/animal) was administered subcutaneously either early in the morning (at 08:00 h), or late in the afternoon (at 18:00 h), for 6 weeks, beginning the day after tumor transplantation. The matched controls were given equal volumes of physiological saline. A careful record of the appearance and growth of the tumor was maintained by examining the animals every morning. At the termination of the experimental schedule, the tumor masses were carefully dissected out, rinsed with normal saline, dried, and weighted on a sensitive Mettler balance. Our results showed that melatonin significantly increased the latency period of the tumor, irrespective of the time of drug administration. Analysis of the final tumor weights showed that afternoon, but not morning, injections of melatonin significantly reduced both the absolute (P less than 0.025) and relative (P less than 0.05) tumor weights in comparison to the saline injected matched control. These results suggest that a) melatonin exhibits its anti-tumor efficacy on MtT/F4 tumor, by delaying the appearance of the tumor, and b) the anti-tumor potential of melatonin is greatly dependent on the time of administration of the drug within the daily light-dark cycle. PMID- 2600763 TI - Stimulation of serotonin-N-acetyltransferase activity in the pineal gland of the mongolian gerbil (Meriones unguiculatus) by intracerebroventricular injection of vasoactive intestinal polypeptide. AB - There is ever-increasing evidence that intrapineal peptides have an important role in the modulation of pineal melatonin synthesis. In the pineal gland of the Mongolian gerbil (Meriones unguiculatus), we have previously shown the presence of VIP-immunoreactive nerve fibers as well as pinealocytic VIP receptors. To assess the functional significance of these findings, 10 microliters of a 1 microM or 1 nM solution of VIP were injected into the lateral ventricle of gerbils over a period of 10 min. Animals were killed 1.5 hr after injection, and the superficial pineal glands were excised and assayed for N-acetyltransferase (NAT) activity. Injection of the 1 microM VIP solution stimulated the NAT activity to values four times the control values. The results are compatible with an in vivo influence on the pineal gland indole metabolism of the nonsympathetic VIP-containing nerve fibers via VIP-receptors present in the gland. PMID- 2600764 TI - Comparisons of sizes of pinealocyte nuclei and pinealocytes in young and adult Chinese hamsters (Cricetulus griseus) under different photoperiod conditions. AB - Semiquantitative electron microscopic observations on pinealocytes of the Chinese hamster (Cricetulus griseus) were made to compare the sizes of pinealocyte nuclei and pinealocytes as a whole, their nuclei and cytoplasm together, over a 24-hr period, between young animals (60-70 days old) and adult animals (120-130 days old) under LD 12:12 and between adults under LD 12:12 and LD 14:10. Under LD 12:12, similar 24-hr rhythms exist in the nuclear area and the area of pinealocytes of young animals, whereas in adults these values exhibit no significant 24-hr rhythm. In adults under LD 14:10, there is no significant 24-hr rhythm in the nuclear area, but the area of pinealocytes shows a statistically significant 24-hr rhythm. Thus, in the Chinese hamster, the relationships between nuclear area and area of pinealocytes with time of day vary, depending on the age of animals as well as different photoperiodic conditions, although they differ only slightly. PMID- 2600765 TI - Foodservice trends in the elderly nutrition program. AB - The foodservice delivery aspects of the federally-funded Elderly Nutrition Program (ENP) were examined via an original survey instrument sent to a random sample of nutrition projects nationally. In comparison to a similar survey conducted a decade ago, projects were more apt to rely on a combination of foodservice mechanisms including caterer contracts, on-site preparation, and use of central kitchens. PMID- 2600766 TI - Nutrition program for the elderly: participants' perception of food quality by type of food service system. AB - A survey of 1028 clients who participated in 21 nutrition sites for the elderly funded by the Suburban Cook County Area Agency on Aging in Chicago, Illinois revealed that participants who received meals prepared on-site were more satisfied with the quality of the meals than participants who received meals that were satellited as hot bulk food or as preplated cook/freeze meals. Participants who judged the meals as fair or poor were more likely than those who rated the food as excellent or good to respond that they would increase their donation if the food were improved. Data from a national survey used as a standard for judging participant satisfaction of food service are presented in this article. PMID- 2600767 TI - The use of texture modified diets among the institutionalized elderly. AB - Directors of nursing in long term health care institutions were surveyed to investigate the use of texture modified diets and feeding practices among the institutionalized elderly. The role of the nursing staff in deciding and recommending the use of texture modified diets in the responding facilities is revealed. Respondents selected reasons for using either texture modified or pureed diets from a list of descriptions of physiological need, behavioral feeding problems and feeding convenience. Correlations between the use of texture modification of diet and feeding dependence are made. A comparison of the extent of use of pureed diets and the reasons for use were reexamined after responding institutions were grouped according to various demographic features and certain feeding practices. PMID- 2600768 TI - The determinants of food choices of the elderly. AB - The increase in individuals over 60 years of age in America must cause professionals from the fields of nutrition, food science, food systems management and the food industry to consider the determinants of food choices and the effects on the overall health and well-being of elderly citizens and those soon to be in their mature years. Income, household composition, food preferences, time, technology, education, good health, attitudes, physiological changes in vision, hearing, taste and smell, psychological and sociological factors all affect the food choices of the elderly. PMID- 2600769 TI - Malnutrition in the nursing home: is it inevitable? PMID- 2600770 TI - Mothers' perceptions of coping behaviors in hospitalized preschool children. AB - This study determined mothers' perceptions of coping in their hospitalized preschool children. Thirty-two mothers were interviewed using open-ended questions to determine their views of coping, what behaviors they described their children using in difficult situations, and what they did to help their children cope. They indicated which of the 40 items on the Children's Coping Strategies Checklist (CCSC) they considered to be coping behaviors. The answers to the open ended questions were content analyzed. Twenty-two mothers described coping as an outcome--that is, as the degree of adaptational success. Seventy-five percent or more of the mothers identified 22 of the CCSC behaviors as coping; 15 of these behaviors were from the subscales of Information Seeking, Seeking Comfort/Help, and Growth/Independence. Eight items were viewed by fewer than half of the mothers as coping, and included regression, denial, withdrawal, and control by preventing events. The mothers described the strategies they used to help their children manage difficult situations; the predominant strategies were providing information and comfort. The implications of the findings are discussed. PMID- 2600771 TI - Oxygenation during chest physiotherapy of very-low-birth-weight infants: relations among fraction of inspired oxygen levels, number of hand ventilations, and transcutaneous oxygen pressure. AB - Chest physiotherapy (CPT) to clear the airway of infants requiring assisted ventilation is a routine procedure in neonatal intensive care units. This study was done to describe the relationships between fraction of inspired oxygen (FiO2) levels and the number of hand ventilations (independent variables) and variations of transcutaneous oxygen pressure (TcPO2) from baseline among intubated very-low birth-weight (VLBW) infants receiving CPT. The study consisted of 30 observations of 13 intubated VLBW infants receiving CPT. Data were obtained by observations during routine CPT procedures performed by the nurses in charge of the infants. Stepwise multiple regression showed that hand ventilations and FiO2 levels significantly accounted for the variability in TcPO2 levels during CPT. Pearson correlation analysis showed that there was a negative correlation between FiO2 and TcPO2 and between the number of hand ventilations and TcPO2. PMID- 2600772 TI - Decision-making of pediatric nurses in nonemergency patient care situations. AB - This study explored the extent to which pediatric nurses value patient education. Ninety-two registered nurses completed and returned the Pediatric Nursing Intervention Priorities Survey (PNIPS). The PNIPS, a tool developed by the investigators, was intended to differentiate four major nursing functions: patient teaching, liaison activity, physical care, and supportive-emotional care. As a result of the study, no significant difference was found between the value nurses placed on patient teaching in relation to the other activities. A significant difference was found, however, between supportive-emotional care and the other options. The influence of a variety of demographic valuables on decision-making was also explored. Implications are drawn for nursing education and nursing practice. PMID- 2600774 TI - AIDS, children, and our fear of death. PMID- 2600773 TI - Using children's diaries as a research instrument. PMID- 2600775 TI - School placement and the oxygen-dependent child. PMID- 2600776 TI - Production of extracellular trypsin and chymotrypsin inhibitors by a Streptomyces Sp. AB - The production of extracellular inhibitors by Streptomyces sp. 1-72, specific either to trypsin (TI-1), or to chymotrypsin (CI-1), was investigated in relation to the cell growth and composition of the cultivation media. The biosynthesis of the inhibitors was found to be of a growth-associated type which reached a maximum level at late exponential phase. All of the investigated carbon sources, including starch, disaccharides and monosaccharides, equally supported the production of both inhibitors, while the effect of the different nitrogen sources considerably varied, some of them being totally ineffective. The sources which mostly supported the biosynthesis of the inhibitors were tryptone (3%) for TI-1, and peptone (3%) for CI-1 respectively. PMID- 2600777 TI - Mycoflora of anise and fennel seeds in Egypt. AB - Using four medium types (glucose-, cellulose-, 50% sucrose- and 10% NaCl-Czapek's agar), it was possible to isolate 15 fungal genera, 78 species and 6 varieties. The collective fungal spectrum varied from one medium to another where the highest number of species (57 species/1000 seeds) was obtained on glucose- and the lowest (31 species/1000 seeds) on 10% NaCl-Czapek's agar. Aspergillus, Penicillium, and sometimes Rhizopus and Chaetomium were the most common genera on the different medium types. The most common fungal species especially on glucose- and cellulose-Czapek's agar were, Aspergillus niger, A. flavus, A. ochraceus, A. fumigatus, A. flavus var. columnaris, Penicillium chrysogenum, Rhizopus stolonifer and Chaetomium globosum. Members of A. glaucus group were more frequently recovered on 10% NaCl- and 50% sucrose-Czapek's agar. PMID- 2600778 TI - Keratinophilic fungi associated with rabbit claws in Egypt. AB - Using the soil plate technique, thirty one species appertaining to twenty three genera were recovered from 160 samples of rabbit claws which were collected from a rabbit farm at Assiut. Of the true keratinophilic fungi Chrysosporium tropicum was the most prevalent where it colonized 56.25% of the samples. Microsporum gypseum was rarely isolated in this study. Among the non-keratinophilic fungi Penicillium funiculosum. P. jenseni and Paccilomyces lilacinus were of low incidence (20%, 19.37% and 14.37% of the samples, respectively). PMID- 2600779 TI - Phaseolotoxin production by Pseudomonas syringae pv. phaseolicola: the influence of temperature. AB - Phaseolotoxin (N-sulphodiaminophosphinyl-ornithyl-alanyl-homoarginine) is a phytotoxic secondary metabolite produced by Pseudomonas syringae pv. phaseolicola. The production of the phytotoxin is strongly regulated by temperature. The optimal temperature for phaseolotoxin production is 18 degrees C. Temperatures in the range between 18 degrees C and 30 degrees C inhibit the production of phaseolotoxin in an increasing manner. By temperature shift experiments and the inhibition of protein synthesis by chloramphenicol it was demonstrated, that the synthesis of enzymes related to toxin synthesis and not the regulation of the activity of the responsible enzyme system is affected by higher temperatures. PMID- 2600780 TI - Screening of microorganisms for enzyme-inhibiting activities. AB - In the course of a screening for extracellular inhibitors of 8 different proteinases 140 actinomycete and 150 mould strains were examined. 130 fungal and 50 actinomycete strains were similarly tested for the production of extracellular inhibitors of dihydrofolate reductase (DHFR) and alkaline phosphatase (APh). Most of the inhibitors found in the culture media of the actinomycete and mould strains were specific against serine proteinases. Inhibitors of DHFR were discovered in the culture media of different actinomycetes and moulds. Inhibiting activities towards APh were found mainly in the fermentation filtrates of the mould strains. The approximate molecular sizes of the active substances were determined by using membrane filtration. PMID- 2600781 TI - Racemization kinetics of enantiomeric oxazepams and stereoselective hydrolysis of enantiomeric oxazepam 3-acetates in rat liver microsomes and brain homogenate. AB - Enantiomers of oxazepam and of 3-O-acyl, 1-N-acyl-3-O-acyl, and 3-O-methyl ether derivatives of oxazepam were resolved on HPLC columns packed with Pirkle's chiral stationary phases [CSP; (R)-N-(3,5-dinitrobenzoyl)phenylglycine or (S)-N-(3,5 dinitrobenzoyl)leucine] bonded either ionically or covalently to spherical particles of gamma-aminopropylsilanized silica, and on a column packed with poly N-acryloyl-(S)-phenylalanine ethyl ester bonded covalently to silica gel (Chiraspher). Resolution was achieved, with several mobile phases of different solvent compositions and with varying chromatographic resolutions, on all of the chiral stationary phases tested. Resolved enantiomers of oxazepam undergo racemization, whereas enantiomers of 3-O-acyl and 3-O-methyl derivatives are stable. Racemization half-lives of oxazepam enantiomers were determined by monitoring changes in ellipticity as a function of time on a spectropolarimeter immediately (within 30 s) following resolution of enantiomers and were found to substantially vary, depending on the solvents used. Rates of hydrolysis of racemic and enantiomeric 3-O-acyl-oxazepams by esterases in liver microsomes and brain homogenate of rats were determined by a simple and sensitive CSP-HPLC method. The relative rate of hydrolysis was 3R greater than racemate much greater than 3S by rat liver microsomes and 3S greater than racemate much greater than 3R by rat brain homogenate. PMID- 2600782 TI - Single dose kinetics of thioridazine and its two psychoactive metabolites in healthy humans: a dose proportionality study. AB - Dose proportionality in some pharmacokinetic parameters for thioridazine and its two active metabolites (mesoridazine and sulforidazine) was investigated in 11 healthy human subjects following oral administration of three single doses (25, 50, and 100 mg) of thioridazine hydrochloride separated in each case by an interval of two weeks. Also, after a further two weeks, another 100-mg dose of thioridazine (divided as 5 mg every 0.5 h) was administered to all the volunteers to investigate the effect of a slow rate of dosage input on the pharmacokinetic parameters of this drug. An HPLC method was used to measure concentrations of thioridazine, mesoridazine, and sulforidazine in plasma samples collected up to 72 h following each dose. Dose proportionality for the three single doses of thioridazine was observed for all three analytes in the area under the plasma concentration versus time curves (AUC infinity 0 or AUCt0) and the maximum plasma concentration (Cmax) in that the relationships between the dose and these parameters were each describable by an equation for a straight line (r2 greater than or equal to 0.8). However, the mean apparent distribution and elimination rate constants for thioridazine and mesoridazine and the mean apparent oral clearance for thioridazine decreased significantly with increasing dose. This suggests nonlinear trends in the elimination kinetics at high doses of thioridazine. When a 100-mg divided oral dose of thioridazine was administered, no statistically significant differences between single and divided doses were observed in the mean AUC infinity 0 or AUCt0 for thioridazine or sulforidazine. A significant decrease in the mean AUC infinity 0 or AUCt0 was observed for mesoridazine after the administration of the divided dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600783 TI - Substituent effects on degradation rates and pathways of cytosine nucleosides. AB - A previous report on the influence of a 6-methyl substituent on cytosine nucleoside degradation proposed that N-glycosyl hydrolysis predominated over the deamination pathway which was characteristic of the unsubstituted parent compounds. The UV absorption data which led to this hypothesis were not conclusive. Evidence for N-glycosyl hydrolysis was indirect and the product concentration was not quantitated. In the present study, specific HPLC methods were employed to assay four cytosine nucleosides and their corresponding bases, thus allowing comparison of the N-glycosyl hydrolysis rate to the overall rate of loss for each nucleoside. These data indicated that the 6-methyl nucleosides underwent partial or complete hydrolysis to yield their corresponding sugars and 6-methylcytosine, which then deaminated to 6-methyluracil. An increase in the reactivity and a change in the reaction products of the 6-methyl nucleosides were attributed to an alteration in conformation. In addition, the 6-methyl arabinosyl nucleoside reacted much faster than the 6-methyl ribosyl nucleoside, presumably due to 2'-OH participation. Degradation of 5-methyl deoxycytidine was also re examined since its degradation was previously attributed solely to N-glycosyl hydrolysis. In the present study, simultaneous deamination and hydrolysis were measured, although N-glycosyl hydrolysis was found to predominate. PMID- 2600784 TI - Factors affecting ceftriaxone plasma protein binding during open heart surgery. AB - Factors most likely contributing to reduced ceftriaxone plasma protein binding in patients undergoing open heart surgery (OHS) were examined. Binding was determined by equilibrium dialysis. It was found that ceftriaxone does not bind significantly to red blood cells, alpha 1-acid glycoprotein, or to protamine, and that the pH of serum did not significantly affect binding. Albumin is the major protein to bind ceftriaxone, and binding decreases with lower albumin concentrations due to fewer binding sites. The binding of ceftriaxone was not affected by the in vitro addition of heparin or methylprednisolone, but high concentrations of methylprednisolone hemisuccinate increased the free fraction of ceftriaxone. Increased concentrations of free fatty acids (FFA) were demonstrated in several patients undergoing OHS. The in vitro addition of palmitic, stearic, linoleic, and oleic acids in high concentrations decreased the binding of ceftriaxone. Ceftriaxone binding in patient samples correlated with the molar ratio of FFA to albumin, but not to either individually. The dual effect of increased FFA and decreased albumin concentrations in OHS patients appears responsible for most of the observed binding alterations. PMID- 2600785 TI - Bioavailability and pharmacokinetics of an oral dopamine prodrug in dogs. AB - The bioavailability and pharmacokinetics of an oral dopamine prodrug, N-(N-acetyl L-methionyl)O,O-bis(ethoxycarbonyl)dopamine (1), were examined in dogs, and the mechanism of its absorption and bioactivation was discussed. Compound 1 showed a plasma dopamine concentration that was several times higher than that of dopamine (DA) following oral administration to dogs, while the plasma concentrations of dopamine-30-sulfate (DA-SO4) and 3,4-dihydroxyphenylacetic acid (DOPAC) are lower in comparison with that of DA. The conversion of 1 to DA occurred in proportion to the dose administered. Compound 1 also showed a plasma DA concentration that was several times higher than that of other DA prodrugs reported hitherto. In dog plasma, in vitro, 1 was converted to its deethoxycarbonylated form, N-(N-acetyl-L methionyl)dopamine (2), while other related compounds, N-(L-methionyl)dopamine (3), N-(L-methionyl)O,O-bis(ethoxycarbonyl)-dopamine (4), and O,O bis(ethoxycarbonyl)dopamine (5), were rapidly converted to DA (however, 2 was stable in plasma). Bioavailability, based on the AUC of DA, 1, 2, and 5 following oral administration to dogs, increased in the following order: 1, 2, 5, and DA. Thus, it was shown that the two protective groups introduced in 1 served to reduce the first-pass metabolism of the DA moiety in the absorption process. It was also confirmed that 1 is converted to 2 or DA in blood, liver, and intestine. PMID- 2600786 TI - Evaluation of biodegradable poly(lactide) pellets prepared by direct compression. AB - Biodegradable pellets intended for either parenteral or oral use were successfully prepared from low molecular weight poly(DL-lactide) (low MW PLA, MW' = 2000) or a relatively high molecular weight poly(L-lactide) (L-PLA, MW = 215,000) sample by a simple direct compression technique without the use of heat or organic solvents. The energy imparted during the compression step caused fusion of the low MW PLA particles. Pellets prepared from low MW PLA swelled considerably before eroding in pH 7.4 buffer, but acted as an enteric matrix in 0.1 M HCl. This was attributed to the high carboxyl endgroup:polymer chain ratio which increased with a decrease in molecular weight. Interactions between salts of basic drugs (quinidine sulfate or propranolol hydrochloride) and the polymeric carboxyl endgroups caused retardation in the drug release from low MW PLA pellets. The drug release from L-PLA pellets was independent of the pH of the dissolution media and drug-polymer interactions were absent. The drug release could be increased by admixing sodium chloride prior to compression, or reduced by dipping the pellets into methylene chloride for a short period of time. PMID- 2600787 TI - A pharmacokinetic model in the rat and rabbit of the direct measurement of mature bone resorption in vivo with [3H]tetracycline. AB - This report presents a pharmacokinetic model in the rat and rabbit of the direct quantification of mature bone resorption in vivo. This is based on a first-order reaction rate describing the release of [3H]tetracycline from bone. Compared with the previous method, the model has two new means of expressing bone resorption. First, resorption rate of bone is precisely represented by explicit parameters derived from the model. Second, resorption rate of the whole skeletal system is measured and demonstrated by means of plasma, renal, and bone kinetics of elimination of the isotope. These are represented by the model parameters, the elimination constant, and the half-life of [3H]tetracycline for plasma, urine, and bone. Four ages of normal Sprague Dawley rats and one age of New Zealand white rabbits of both sexes were prelabeled extensively with [3H]tetracycline in utero or during 10 to 84 d of age. Following 1-21 d after the end of prelabeling, the loss of the isotope from femur into plasma and urine was measured at weekly intervals to determine bone resorption of mineral in vivo. The elimination constants of the isotope per day in plasma were -0.148 in weaning rats (4-7 weeks), -0.071 in adolescent rats (10-14 weeks), and -0.025 in mature rats (15-23 weeks). The urinary elimination constants of the isotope per day were 74, 76, and 76% of those in plasma in weaning, adolescent, and mature rats, respectively. The half-lives of the isotope in the femur were 10 d in neonatal rats (0-2 weeks), 32 d in weaning rats, 63 d in adolescent rats, and 198 d in mature rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600788 TI - Technetium-99m labeled p-aminohippuric acid analogues: renal function agents. AB - A number of p-aminohippuric acid analogues were synthesized in order to develop clinically useful 99mTc-labeled radiopharmaceuticals for evaluation of renal function measurements. Stable 99mTc-labeled complexes were formed at pH 5.7 using a Sn(II) reduction method with all derivatives. The newly synthesized complexes were screened utilizing biodistribution studies in small animals. All complexes were excreted via the GU tract within 60 min post iv administration, with no significant activity in GI tract and liver. The [99mTc]methyl-PAHIDA complex showed optimal biodistribution among these analogues. Further investigation is needed to determine if these derivatives may be used to replace [131I]o iodohippuric acid for the evaluation of renal function. PMID- 2600789 TI - Preparation and properties of (R)-(-)-1-azabicyclo[2.2.2]oct-3-yl- (R)-(+)-alpha hydroxy-alpha-(4-[125I]iodophenyl)-alpha-phenyl acetate and (R)-(-)-1 azabicyclo[2.2.2]oct-3-yl-(S)-(-)-alpha-hydroxy-alpha- (4-[125I]iodophenyl)-alpha phenyl acetate as potential radiopharmaceuticals. AB - rac-4-Nitrobenzilic acid was synthesized and resolved with quinidine and quinine to give the corresponding (R)- and (S)-salts. The resolved diastereomeric salts were converted to (R)- and (S)-4-nitrobenzilic acids and subsequent esterification gave their corresponding ethyl esters. Transesterification with (R)-(-)-3-quinuclidinol afforded (R)-(-)-1-azabicyclo[2.2.2]oct-3-yl-(R)-(+) alpha-hydroxy-alpha- (4-nitrophenyl)-alpha-phenyl acetate and (R)-(-)-1 azabicyclo[2.2.2]oct-3-yl-(S)-(-)-alpha-hydroxy- alpha-(4-nitrophenyl)-alpha phenyl acetate. After hydrogenation, the (R,R)- and (R,S)-amines were converted to the respective triazene derivatives. The triazene derivatives reacted with sodium [125I]iodide to give (R)-(-)-1-azabicyclo[2.2.2]oct-3-yl-(R)-(+)- alpha hydroxy-alpha-(4-[125I]iodophenyl)-alpha-phenyl acetate and (R)-(-)-1 azabicyclo[2.2.2]oct-3-yl-(S)-(-)-alpha-hydroxy- alpha-(4-[125I]iodophenyl)-alpha phenyl acetate. The evaluation of their affinities to muscarinic acetylcholine receptors (MAcChR) shows that (R)-(-)-1-azabicyclo[2.2.2]oct-3-yl-(S)-(-)-alpha hydroxy-alpha-(4- [125I]iodophenyl)-alpha-phenyl acetate exhibits an affinity for the MAcChR from corpus striatum that is approximately threefold lower than that of (R)-(-)-1-azabicyclo[2.2.2]oct-3-yl-(R)-(+)-alpha-hydroxy-alpha-(4- [125I]iodophenyl)-alpha-phenyl acetate. PMID- 2600790 TI - Improved anticonvulsant activity of phenytoin by a redox brain delivery system. III: Brain uptake and pharmacological effects. AB - Phenytoin (DPH) was delivered to the brain by a dihydropyridine in equilibrium pyridinium salt redox system, which was evaluated for anticonvulsant activity. Following iv injection of the lipophilic delivery system of DPH (2) to rats, concentrations of DPH were lower but sustained and, after 30 min, essentially the same as the levels after equimolar administration of DPH. While 2 delivered the same levels of DPH to the brain as DPH did, it was twice as potent as DPH in rats (ED50 was 7.5 mumol/kg for 2 and 14.2 mumol/kg for DPH) and mice (2: 10.5; DPH: 23.9) against maximal electroshock seizures (MES), and seven times more potent in mice (2: 10.0, DPH: 70.6) against maximal pentylenetetrazole seizures (MPS). Moreover, 2 was active against pentylenetetrazole threshold seizures (PTS) in mice and rats (ED50 = 44.1 and 40.5 mumol/kg, respectively), while DPH was ineffective (up to a dose of 79.2 mumol/kg). After evaluation of acute neurological toxicity in rats, 2 was found to possess 1.5 times higher a protective index (for MES) than DPH. It appeared also that while DPH was 2.9 times less sensitive to MPS than to MES, 2 was equally potent to both types of convulsions. Thus, the data indicate that 2 delivered DPH more efficiently to the brain. The better anticonvulsant activity (quantitatively as well as qualitatively) of 2 can be explained on the basis of an improved distribution in the brain due to its higher lipophilicity, and by favorable regional differences in the rates of conversion of 2 to DPH at the convulsing foci. PMID- 2600791 TI - Chlorpheniramine dissolution and relative urinary excretion from commercial products. AB - Dissolution profiles were determined for seven commercially available nonprescription solid dosage forms containing chlorpheniramine (four sustained release and three immediate release). An in vitro pH change method used to simulate GI transit produced dissolution profiles for some similarly labeled products which were significantly nonequivalent. One product failed to release its chlorpheniramine even when ground in a mortar and pestle in HCl solution, but did release drug in H3PO4 solution. A small (four subjects) relative bioavailability study based on average cumulative excretion of intact drug in urine gave results in parallel with substantially nonequivalent dissolution data for three products. PMID- 2600792 TI - Center of gravity of drug level curves: a model-independent parameter useful in bioavailability studies. AB - The center of gravity (CG) of a drug level curve [c(t)] has the time coordinate AUMC/AUC and the concentration coordinate AUCC/2AUC, where AUC, AUMC, and AUCC are the integrals from time t = zero to t = infinity of c(t), tc(t), and c(t).c(t), respectively. An algorithm and computer program for determining CG when c(t) is given by a sum of exponentials is presented and its use is demonstrated with oral cimetidine data. Simulations indicate that the CG appears more suitable for comparison of absorption rates than mean absorption time (MAT) parameters. The limitation of the MAT parameter is due to the fact that this parameter is scale independent in that it only considers the shape and not the magnitude of the drug level or absorption rate curve. The MAT is therefore independent of the extent (F) of absorption. This limitation is not shared by the CG. When dealing with first-order absorption, the absorption rate of drug from product A will consistently (all t greater than 0) be larger than the absorption rate from product B (tested in the same subject) if MATA greater than MATB and AUCA/AUCB greater than MATA/MATB (assuming a time-invariant linear disposition). The above inequality relationships strongly contrast the common thinking about the "nonproblematic" use of MAT in absorption rate comparisons. Since both CG and MAT suffer some fundamental limitations, it is recommended that whenever problems arise, one should compare absorption rates by nonparametric system analysis methods (e.g., deconvolution) if possible. PMID- 2600793 TI - Preformulation studies of acetazolamide: effect of pH, two buffer species, ionic strength, and temperature on its stability. AB - Using an HPLC method, the effect of pH, two buffer species (phosphate and citrate), ionic strength, and temperature on the stability of acetozolamide has been studied. The optimum pH of stability appears to be 4. The buffers and ionic strength did not affect the decomposition constant. There was a direct relationship between the activation energies and pH values, with an energy of activation (Ea) value of 16.61 kcal/mol at pH 4. The un-ionized acetazolamide is subject to specific acid-base catalysis. The KH and KOH values have been estimated to be 0.23 and 1.56 d-1, respectively. These preformulation studies can be used to develop a stable oral liquid dosage form of acetazolamide. PMID- 2600794 TI - Use of liquid chromatography and mass spectroscopy to select an oligomer representative of polyester hydrolysis pathways. AB - An analytical method has been developed for the simultaneous determination of a series of low molecular weight biodegradable polyesters and its degradation products. The separation is accomplished using a strong anion exchange HPLC column. The polyester and its degradation products are identified by fast atom bombardment mass spectrometry. This technique will enable one to establish the polyester hydrolysis pathways and determine accurate kinetic parameters. PMID- 2600795 TI - Simultaneous determinations of tolbutamide and its hydroxy and carboxy metabolites in serum and urine: application to pharmacokinetic studies of tolbutamide in the rat. AB - Methods of analysis of tolbutamide (1) and its hydroxylated (2) and carboxylated (3) metabolites in serum and urine based on high-performance liquid chromatography were developed. The separation was performed on a Apex ODS column in the isocratic mode using a mobile phase composed of 22.5% acetonitrile, 77.5% Sorensen phosphate buffer (pH 7.0), and 0.30 mL of tetrabutylammonium phosphate reagent (Pic A). The compounds were detected at 254 mm. The retention times of 3, 2, 1, and the internal standard chlorpropamide were 3.1, 4.1, 14.8, and 10.0 min, respectively. These conditions were suitable for the simultaneous quantitation of 1, 2, and 3 in serum or plasma samples, but not for the determination of metabolites 2 and 3 in urine. For the analysis of 2 and 3 in urine, the mobile phase was modified to 18% acetonitrile, 82% Sorensen phosphate buffer (pH 7.0), and 0.35 mL of Pic A. Under these conditions, the retention times of the carboxy and hydroxylated metabolites and the internal standard salicylic acid were 4.6, 6.7, and 8.1 min, respectively. These methods were applied to study the pharmacokinetics of 1 administered intravenously and intraperitoneally to the rat. Tolbutamide was almost completely recovered as metabolites 2 and 3 in the urine within 24 h. PMID- 2600796 TI - Pharmacokinetics and biotransformation of hydralazine acetone hydrazone, a metabolite of hydralazine, in the rat. AB - The pharmacokinetics of hydralazine acetone hydrazone (HAH), which is a metabolite of hydralazine (HP), was investigated after iv administration to rats. Plasma concentrations of HAH, HP, and hydralazine pyruvic acid hydrazone (HPH) were simultaneously determined by a specific HPLC method. A five-compartment pharmacokinetic model was presented to elucidate the disposition of HAH and two products, HP and HPH. The parameters used in the model were obtained by administering each of the three compounds (10 mg/kg) separately. The proposed model described the experimental data well and the model parameters were close to the model-independent values. After HP administration, HPH appeared rapidly in plasma, but the HPH availability from HP amounted to only 17.8 +/- 3.7%, based on the comparison between the area under the plasma concentration curves of formed and iv HPH. The formation of HP from HAH in the systemic circulation was demonstrated, but formed HP disappeared rapidly. The fraction of HAH available to the systemic circulation as HPH was extremely low (7.8 +/- 2.2%), indicating that the conversion of HAH to HP was not so extensive. The present results support the hypotheses that HPH is formed via the direct reaction of HAH with pyruvic acid and that the secondary formation is mediated by conversion to HP. PMID- 2600797 TI - Analysis of 2-cyano-1-methyl-3-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3 yl phenyl]guanidine in dog plasma by liquid-solid extraction and reversed-phase high-performance liquid chromatography. AB - A method for the determination of 2-cyano-1-methyl-3-[4-(4-methyl-6-oxo-1,4,5,6 tetrahydropyridazin- 3- yl)phenyl]guanidine (SK&F94836, 1) in plasma is presented. The method involves liquid-solid extraction of the drug by C18 cassettes, with subsequent elution by an AASP LC module for determination by HPLC with UV detection. The assay is rapid, precise, accurate, and specific. The between-day CV values over the concentration range 50-500 ng/mL are 4% or less; this rises to 8% at 25 ng/mL. The corresponding between-day bias is less than 1% over the same range of concentrations. The limit of quantification is 25 ng/mL and the assay can be used for measuring 1 in samples from preclinical studies following either oral or intravenous administration of the compound. PMID- 2600798 TI - Population pharmacokinetics of mitoxantrone performed by a NONMEM method. AB - To date, the pharmacokinetics of mitoxantrone (1,4-dihydroxy-5,8-bis[[2-[(2- hydroxyethyl)amino]ethyl]amino]anthraquinone) has been described either by an open two- or three-compartment model, showing high interindividual variability. In order to evaluate this variability, residual intraindividual variability, and measurement error, we carried out a population study. A sensitive HPLC method allowed analysis of blood samples drawn from 21 patients with breast cancer or acute nonlymphocytic leukemia. Individual data treatment (22 kinetics) using weighted nonlinear least squares regression confirmed the huge interindividual variability whatever the administration protocol of mitoxantrone: bi- or tri exponential models fitted the data. The NONMEM population method used herein describes all concentration-time curves by a single three-compartment model, considering biphasic kinetics as fragmentary data. Residual intraindividual variability was 21.4%. Population mean values (+/- interindividual SD) of clearance, terminal half-life, and total volume of distribution were, respectively, 23.40 (+/- 10.76) L/h, 46.87 (+/- 12.18) h, and 385.49 (+/- 196.60) L. These results are of particular interest in clinical routines to calculate dosage regimens by Bayesian estimation methods. PMID- 2600799 TI - Ketoprofen enantiomers in synovial fluid. PMID- 2600800 TI - 5-Hydroxytryptamine2 receptor antagonist activity of the acid metabolite (1 isopropyl dihydrolysergic acid) of the ergoline ester, sergolexole (LY281067). AB - The ergoline esters, LY53857 [6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid 2-hydroxy-1-methylpropylester (Z)-2-butenedioate] and sergolexole (LY281067) ([trans-(8 beta)]6-methyl-1-[1-methylethyl]ergoline-8-carboxylic acid, 4 methoxycyclohexyl ester (maleate salt] are potent 5-hydroxytryptamine2 (5-HT2) receptor antagonists in vivo and in vitro. Ester hydrolysis of either compound results in the formation of 1-isopropyl dihydrolysergic acid which in rats is a major metabolite of these ergoline esters. The present study details the pharmacological activity of 1-isopropyl dihydrolysergic acid and examines its relative contribution to the 5-HT2 receptor antagonism seen after sergolexole in rats. In vitro, 1-isopropyl dihydrolysergic acid was a competitive antagonist of 5-HT2 receptors in the rat jugular vein, with a dissociation constant approximating 10(-7) M. After i.v. administration to pithed rats, 1-isopropyl dihydrolysergic acid also antagonized the pressor response produced by serotonin, an in vivo estimate of vascular 5-HT2 receptor blockade. In fact, after i.v. administration, 1-isopropyl dihydrolysergic acid was nearly one-third as potent as sergolexole. After i.p. administration, 1-isopropyl dihydrolysergic acid was approximately one-tenth to one-thirtieth as potent as sergolexole. Likewise, 1 isopropyl dihydrolysergic acid antagonized central 5-HT receptors as measured by blockade of quipazine-induced increases in serum corticosterone concentration in rats and was approximately one-twentieth as potent as sergolexole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600801 TI - Splanchnic tissues are a major part of the rapid distribution spaces of inulin, urea and theophylline. AB - Distribution of kinetics of inulin, [14C]urea and theophylline were studied in five anesthetized dogs after splenectomy and gastrointestinal resection. Distribution was modeled with three-compartment mammillary systems in which the central compartment corresponds to intravascular space and the two peripheral compartments have different rates of transcapillary exchange. Compared with results in intact dogs, the surgical procedure removed between 41 and 55% of the rapidly equilibrating tissues and reduced the permeability coefficient-surface area products for the rapidly equilibrating inulin and urea compartments proportionately. This is consistent with the concept that splanchnic organs equilibrate rapidly with inulin and urea because they are supplied by fenestrated and discontinuous capillaries that are prominent in the splanchnic vascular bed. However, splanchnic organs probably do not contain all rapidly equilibrating tissues, and somatic tissues may contribute as much as 36 and 22%, respectively, of the rapidly equilibrating inulin and urea compartments. Cardiac output averaged 2.87 +/- 0.86 liters/min and was similar to the sum of compartmental blood flows estimated from the intercompartmental clearances of urea and inulin (2.74 +/- 0.96 liters/min) and to the sum of theophylline intercompartmental clearances (2.62 +/- 0.74 liters/min). Theophylline intercompartmental clearance to each peripheral compartment was similar to estimated compartmental blood flow. PMID- 2600802 TI - Pharmacodynamic modeling of verapamil effects under steady-state and nonsteady state conditions. AB - Pharmacodynamic models relating the plasma concentration (Cp) of verapamil to the drug's effect (E) on the P-R interval were investigated after single dose infusions of (0.15-0.22 mg/kg) verapamil in 22 normal subjects. Model predictions of the steady-state Cp-E relationship were then compared to results from actual steady-state drug infusions in the same subjects. Two methods of estimating the steady-state concentration response relationship from the single dose data were examined: 1) the relationship of descending limb Cp vs. E and 2) the relationship of estimated effect site concentrations (Ce) vs. E. When compared to experimental steady-state measurements, the absolute errors of predictions from the Ce vs. E method were less than those from the Cp vs. E predictions (6.8 +/- 4.4 vs. 9.6 +/ 6.6, mean +/- S.D.). Similarly, the slope of the linear regression of E on Cp differed more from the observed steady-state slope than the slope of E on Ce. Sigmoid Emax models fit to Cp vs. E. data gave false Emax values even when data immediately following drug infusion were disregarded whereas Ce vs. E plots demonstrated that Emax was not reached (and Ce much less than Cp). Neither the postinfusion (descending limb) Cp vs. E nor Ce vs. E plots allowed analysis of higher concentration vs. effect relationships after usual (0.15-0.22 mg/kg) doses of verapamil. In summary, we have demonstrated that nonsteady-state postdrug infusion effect vs. plasma concentration data for verapamil does not reflect the true steady-state relationship and that use of a model to estimate effect site concentration provides a closer estimate of the true steady-state relationship. PMID- 2600803 TI - Altered hepatic junctional permeability, bile acid excretion and glutathione efflux during oxidant challenge. AB - Hepatobiliary functions during administration of the thiol-oxidizing agents t butyl hydroperoxide, hydrogen peroxide, diamide and menadione were monitored in the isolated rat liver perfused with a recirculating fluorocarbon emulsion. Because these agents are detoxified largely by glutathione-dependent mechanisms, efflux of reduced glutathione and glutathione disulfide into bile and perfusate was measured, along with bile flow, excretion of endogenous bile acids, lactate dehydrogenase release and the bile/perfusate ratios of [14C]sucrose (a marker of junctional permeability) and [3H]polyethylene glycol-900 (a substance concentrated in bile, presumably by a vesicular transport pathway). All agents enhanced the rate of glutathione efflux from the liver, reflecting increased formation of glutathione disulfide. At low doses of the thiol-oxidants, most of the additional glutathione released by the liver appeared in bile, whereas at higher doses the fraction appearing in the sinusoidal circulation increased. This enhanced glutathione disulfide release was associated with a decrease in endogenous bile acid excretion and in the bile/perfusate ratio of [3H]polyethylene glycol, and an increase in the bile/perfusate ratio of [14C]sucrose. These deleterious changes were reversible, and were noted at doses that had no effect on lactate dehydrogenase release, and only small effects on perfusion pressure. Bile flow was decreased by t-butyl hydroperoxide and H2O2, and increased by diamide (100 mumol) and menadione (20 mumol). These results indicate that alterations in hepatic thiol-redox status lead to an impairment of bile acid excretion, junctional integrity and bile formation. These functional parameters appear sensitive to the effects of oxidizing agents, and probably contribute to the pathogenesis of hepatobiliary dysfunction during the metabolism of certain drugs and xenobiotics. PMID- 2600804 TI - Angiotensin II vascular receptors in fowl aorta: binding specificity and modulation by divalent cations and guanine nucleotides. AB - In the domestic fowl, angiotensin (ANG) II causes a unique vasodepressor response in vivo and vascular relaxation of aortic rings in vitro that appear to be mediated by ANG II receptors. In initial studies using radioligand binding techniques, we identified specific vascular ANG II receptors in the fowl aorta. In the present study, we have characterized fowl vascular ANG II receptors in terms of binding specificity and their modulation by divalent cations and guanine nucleotide, to understand how the fowl receptor might differ from mammalian vascular ANG II receptors that mediate vasoconstriction. Competitive displacement of [125I] ANG II binding by ANG agonist and antagonist analogs revealed a unique pattern of receptor specificity, with the potency rank order: [Asn1, Val5]ANG II greater than [Asp1, Ile5]ANG II greater than [Asp1, Val5, Ser9] ANG I = [Asp1, Val5]ANG II much greater than [Val5]ANG III greater than [sarcosine(Sar)1, Ile5]ANG II greater than [Sar1, Ile8]ANG II much greater than [Sar1, Thr8]ANG II. Divalent cations (Ca++, Mg++ and Mn++) inhibited equilibrium radioligand binding by as much as 50% at 100 mM, with the potency order: Ca++ greater than Mn++ greater than Mg++. Mg++ and Mn++ stimulated binding very slightly (110%) at low doses (1-10 mM). The stable guanine nucleotide analog 5'-guanylyl imidodiphosphate inhibited equilibrium radioligand binding moderately (15% at 100 microM) in the presence of 10 mM MgCl2, but failed to alter the dissociation rate of receptor-bound ligand (half-time = 10.92 min). These results suggest that fowl vascular ANG II receptors exhibit specificity and regulatory properties fundamentally different from those of mammalian vascular ANG II receptors. PMID- 2600805 TI - Interactions of noncompetitive inhibitors with nicotinic receptors in the rat brain. AB - This study was performed to determine how drugs that inhibit the function of peripheral nicotinic receptors (noncompetitive inhibitors), interact with nicotinic receptors in the brain. By using [3H]MCC (methylcarbamylcholine ) as a ligand for nicotinic receptors, competition studies at a fixed concentration of radioligand and saturation studies were performed with various noncompetitive inhibitors. [3H]MCC labeled high affinity nicotinic receptor sites in the rat brain at equilibrium. The sites appeared to represent desensitized nicotinic receptors, comprising a fraction of the total pool of these receptors. At micromolar concentrations, noncompetitive inhibitors interacted distinctively with [3H]MCC binding sites. Mecamylamine behaved as an allosteric inhibitor, as it decreased the apparent density of [3H]MCC binding sites. Tetracaine had mixed allosteric/competitive properties, reducing both the density and the affinity of binding. Chlorpromazine manifested a biphasic effect, increasing receptor density at concentrations of approximately 50 to 500 microM and reducing the affinity at higher concentrations. The results suggest that noncompetitive inhibitors bind to different, but interacting sites associated with desensitized nicotinic receptors in the brain, as well as to recognition sites for acetylcholine. PMID- 2600806 TI - AY-31,906, a novel high ceiling diuretic: characterization of its relative potassium-sparing actions in rats and dogs. AB - AY-31,906, exo-2-amino-4-[(bicyclo[2.2.1]hept-2-yl)amino-N-[[1- methylethyl)amino]carbonyl]-5-pyrimidinesulfonamide, exhibited potent diuretic and natriuretic activity in rats and dogs. After p.o. administration, AY-31,906 was 1.5- and 12.3-times more potent as a natriuretic than furosemide in rats and dogs, respectively, whereas it was 0.5- and 6.1-times as potent after i.v. administration. The maximum natriuretic effect of AY-31,906 in both species was similar to that observed with furosemide. At equiactive natriuretic p.o. doses in both species, AY-31,906 produced a greater increase in the urinary ratio of Na/K than furosemide, indicating a relative potassium-sparing effect. AY-31,906 produced significant increases in the fractional excretion of sodium and chloride in dogs at a dose that produced no statistically significant changes in the fractional excretion of potassium, glomerular filtration rate or renal plasma flow. After p.o. administration, the onset of activity of AY-31,906 occurred within the 1st hr in both rats and dogs and preliminary data demonstrated that the activity lasted for approximately 2 hr in rats and 4 hr in dogs. Clearance studies in conscious dogs suggest that AY-31,906 inhibited electrolyte reabsorption in the ascending limb of the loop of Henle and, unlike furosemide, AY-31,906 had no activity at the proximal tubule. These results indicate that AY 31,906 is a potent, high ceiling diuretic with relative potassium-sparing properties. The compound is well absorbed after p.o. administration with diuretic activity occurring in the 1st hr. PMID- 2600807 TI - Noncyclic vasopressin analogs are effective diuretics in conscious rats. AB - Linear vasopressin analogs lacking a cyclic hexapeptide ring have recently been reported to possess vasopressin antagonist activity. In conscious, chronically catheterized, euhydrated Sprague-Dawley rats, we have compared the effects of two noncyclic vasopressin analogs, peptide 1 ([1-admantaneacetic acid,2-(O-ethyl)-D tyr,4-val,6-(2-aminobutyric acid),9-arg]arginine vasopressin) and peptide 2 ([1 propionic acid, 2-(O-ethyl)-D-tyr,4-val,6-(2-aminobutyric acid),9- arg]arginine vasopressin), with a cyclic arginine vasopressin antagonist (SK&F 105494; [1-des cysteine, cyclo(2-O-ethyl-D-tyrosine,6-L-(2-amino-6,6-cyclopentamethylene suberic acid], 4-valine,7-arginine,8-D-arginine, 9-des glycine]-vasopressin). All three analogs caused a dose-dependent increase in urine flow by increasing free-water clearance without significantly changing osmotic clearance or sodium excretion, indicating true functional vasopressin antagonism. Peptides 1 and 2 were as efficacious in inducing a diuresis as SK&F 105494. The order of diuretic potency among the three analogs in vivo was the same as the order of potency determined by in vitro binding to rat renal membrane homogenates, suggesting that the analogs exerted their diuretic effect by acting at renal vasopressin receptors. Thus, noncyclic vasopressin analogs, which are easier to synthesize then cyclic structures, could provide new strategies in the design of drugs for the treatment of water balance disorders. PMID- 2600808 TI - Effect of the novel cholecystokinin receptor antagonist CR-1392 on cholecystokinin-induced antroduodenal and pyloric motor activity in vivo. AB - The effects of i.a. injected cholecystokinin (CCK)-octapeptide on pyloric and antroduodenal motility, measured with strain gauges and combined side hole-sleeve manometry, were investigated in 16 dogs in vivo. CCK-octapeptide (OP) induced strong pyloric contractions when injected into the pylorus (threshold of 2 x 10( 13) mol; ED50, 8 x 10(-13) mol). Similar responses were obtained in the distal antrum (threshold, 6 x 10(-13) mol; ED50, 3 x 10(-12) mol) and the proximal duodenum (threshold, 5 x 10(-13) mol; ED50, 3 x 10(-12) mol). The nonsulfated form of CCK-OP was about 2 to 3 log units less potent in eliciting these excitatory responses in the pylorus (threshold, 9 x 10(-10) mol). Atropine shifted the dose-response curve of CCK-OP in pylorus, duodenum and antrum to the right suggesting a neural action of CCK-OP. However, an excitatory effect of CCK OP was still present after neural blockade with tetrodotoxin i.a. Therefore, there was probably a muscular as well as a neural site of action of CCK-OP in these tissues. Systemic application of the novel CCK-antagonist CR-1392 in a dose of 1.2 mg/kg i.v. plus 100 micrograms i.a. shifted the dose-response curve of CCK OP 1 log unit to the right without affecting the dose-response curve to acetylcholine. This dose of CR-1392 did not interfere with the pyloric motor responses to duodenal field stimulation or to intraduodenal acid infusion. These results demonstrate the dual peripheral action on nerve and muscle of CCK-OP in the pylorus in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600809 TI - Furosemide directly stimulates prostaglandin E2 production in the thick ascending limb of Henle's loop. AB - Studies were conducted to investigate direct effects of loop diuretics on prostaglandin E2 (PGE2) production using microdissected nephron segments. At first, the effect of indomethacin on the diuretic response to furosemide was re evaluated in anesthetized rats. Indomethacin significantly attenuated the diuretic, natriuretic and chloruretic effects of furosemide without significantly affecting inulin and p-aminohippurate clearance or filtration fraction. But, in nondiuretic states, indomethacin had no significant effects on these parameters. Furosemide, ethacrynic acid and bumetanide significantly increased PGE2 production in cortical and medullary thick ascending limbs of Henle's loop (P less than .001), but not PGE2 production in the cortical and outer medullary collecting tubules. The effect of furosemide on PGE2 production in CTAL was dose dependent, and higher concentrations of of furosemide than 10(-6) M significantly increased PGE2 production. On the other hand, chlorothiazide showed no PGE2 productive stimulation in these four nephron segments. This study demonstrates that the enhanced PGE2 production in the thick ascending limb of Henle's loop by furosemide and other loop diuretics is one possible mechanism of these drugs. PMID- 2600810 TI - Acetylcholinesterase reactivators antagonize epileptiform bursting induced by paraoxon in guinea pig hippocampal slices. AB - The electrophysiological actions of paraoxon, an irreversible blocker of acetylcholinesterase, and their antagonism by a series of organophosphate cholinesterase reactivators, were studied in area CA1 of the guinea pig hippocampus in vitro. To avoid indirect effects elicited by excitation of CA3 neurons, the CA2/3 regions were removed routinely before the recording of extracellular field potentials in CA1. Under these conditions, paraoxon (1 microM) induced regular burst activity (rate, 2-10/min; amplitude, 0.2-1 mV; duration, 100-500 msec). The antagonism of this burst activity by atropine (0.3 1.0 microM) and pirenzepine (1.0 microM) suggested the involvement of muscarinic cholinoceptors in the mediation of this response. The reduction in frequency of paraoxon-induced bursting by the cholinesterase reactivators was taken as an index of their efficacies. The four oxime compounds tested were all active in the low micromolar range (rank order of potencies: obidoxime greater than HGG 12 = HLo 7 greater than Hl 6). In experiments without paraoxon, these oximes did not depress either evoked population spikes in normal artificial cerebrospinal fluid or bursts induced by superfusion with Mg++-free artificial cerebrospinal fluid. Thus, an unspecific inhibitory effect of oximes can be excluded. It is concluded that the in vitro hippocampus provides a suitable system for the quantitative electrophysiological evaluation of cholinesterase reactivators in the central nervous system. PMID- 2600811 TI - Characterization and distribution of P2-purinoceptor subtypes in rat pulmonary vessels. AB - To characterize P2-purinoceptors in pulmonary vessels we have examined the effects of ATP analogs on rat isolated pulmonary artery and vein in vitro. The rank order of potency for causing vasoconstriction was: alpha,beta-methylene-ATP (alpha,beta-meATP) greater than beta,gamma-methylene-ATP (beta,gamma-meATP) greater than 2-methylthio-ATP (2m.S.ATP) greater than ATP for arteries; and alpha,beta-meATP much greater than beta,gamma-meATP = 2m.S.ATP greater than ATP for veins, indicating that a P2x receptor was involved. The contractile response to these analogs was virtually abolished after desensitization of P2x-receptors by alpha,beta-meATP. Removal of the endothelial cells enhanced the contractile responses to all of the ATP analogs in both arteries and veins. The rank order of potency for vasodilatation was 2m.S.ATP much greater than ATP = beta,gamma-meATP much greater than alpha,beta-meATP for arteries and 2m.S.ATP much greater than ATP = beta-gamma-meATP, with alpha,beta-meATP being no effect for veins, indicating a P2y receptor. Pretreatment of the pulmonary arteries with the P2y antagonist reactive blue 2 caused a rightward shift of the dose-response curves to 2m.S.ATP, ATP and beta,gamma-meATP. Reactive blue 2 was only used with the pulmonary arteries. Removal of the endothelium converted the relaxant responses to all the ATP analogs (except to ATP in pulmonary artery) to further contraction. In the pulmonary artery, the small endothelium-independent relaxation induced by ATP was abolished completely by pretreating the vessels with 100 microM theophylline (a P1-purinoceptor antagonist), suggesting that it was due to conversion of ATP to adenosine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600812 TI - The binary toxin produced by Clostridium botulinum enters cells by receptor mediated endocytosis to exert its pharmacologic effects. AB - The binary toxin produced by Clostridium botulinum produced dose-dependent changes in cell morphology, characterized by loss of extensions and rounding. The effects were obtained when both polypeptide chains of the toxin were added to cells at 37 degrees C; the effects were inhibited by low temperature (4 degrees C) and by sodium azide (15 mM). Attachment of the heavy polypeptide chain to cells before the light polypeptide chain was necessary to produce cell poisoning. When cells were maintained at 4 degrees C, the receptor-bound heavy chain remained at the cell surface and accessible to the light chain. When cells were maintained at 37 degrees C, the receptor-bound heavy chain was internalized and no longer accessible to light chain. Drugs that antagonize receptor-mediated endocytosis, such as ammonium chloride and methylamine hydrochloride, inhibited internalization of the heavy chain-light chain complex. These drugs did not antagonize receptor binding by the heavy chain or did they inhibit mono(ADP ribosyl)ation in broken cells by the light chain. However, they did diminish the amount of mono(ADP-ribosyl)ation produced by holotoxin in intact cells. The data indicate that receptor-mediated endocytosis is an essential step in the ability of the toxin to poison cells. PMID- 2600813 TI - Adenosine A1 receptor activation mediates suppression of (-) bicuculline methiodide-induced seizures in rat prepiriform cortex. AB - The protective effects of a series of stable adenosine analogs against generalized seizures initiated by focal injection of bicuculline methiodide into the rat prepiriform cortex (PPC) were studied by microinjection of these compounds into this brain area. The adenosine agonists, 5'-N-(ethyl)carboxamido adenosine (NECA), cyclohexyladenosine, cyclopentyadenosine, 2-chloroadenosine and R- and S-phenylisopropyladenosine (R- and S-PIA), protected animals against seizures in a dose-dependent, and extremely potent manner. NECA, the most potent compound evaluated, completely prevented seizures at doses greater than or equal to 6.8 pmol. In contrast, heroic doses of the A2 selective ligand, 2 phenylaminoadenosine, afforded no protection against seizures. The rank order of potency of these compounds in suppressing seizures is as follows: NECA greater than cyclohexyladenosine greater than cyclopentyladenosine greater than or equal to R-PIA greater than 2-chloroadenosine greater than S-PIA much greater than 2 phenylaminoadenosine. These data suggest that the antiseizure activity of these compounds in the PPC results from activation of A1 adenosine receptors. Quantitative autoradiographic analysis of the distribution of tritiated adenosine agonists 30 min after microinjection in the PPC reveals that [3H]NECA diffuses to a significantly greater extent than R-[3H]PIA, which may contribute to the relatively greater potency of the former compound in suppressing bicuculline methiodide-induced seizures. These results suggest that adenosine A1 receptors may participate in the normal inhibitory regulation of the PPC, a forebrain area which may play a significant role in the pathobiology of epilepsy. PMID- 2600814 TI - Differential blocking effects of atropine and gallamine on negative chronotropic and dromotropic responses to vagus stimulation in anesthetized dogs. AB - The negative dromotropic response to cervical vagus stimulation was inhibited less than the negative chronotropic response to cervical vagus stimulation by the same dose of atropine in neurally decentralized, anesthetized dogs. Atropine and gallamine bind different muscarinic binding sites. We thus investigated the blocking effects of atropine and gallamine on the negative chronotropic and dromotropic responses to stimulation of the vagus nerves. We stimulated the intracardiac vagus nerves to the SA nodal area (sinoatrial fat pad stimulation) or to the atrioventricular nodal area (atrioventricular fat pad stimulation). Sinoatrial fat pad stimulation increased the sinus cycle length. Atrioventricular fat pad stimulation increased atrioventricular conduction time without affecting the cycle length. Atropine inhibited the chronotropic response to sinoatrial fat pad stimulation and the dromotropic response to atrioventricular fat pad stimulation in a dose-dependent manner. The ID50 for the chronotropic responses was less than that for the dromotropic responses. In contrast, gallamine inhibited the chronotropic and dromotropic responses in a similar dose-dependent manner. Physostigmine potentiated the chronotropic and dromotropic responses similarly but it did not change the blocking effects of atropine on the cardiac responses. These results suggest that the binding properties of the muscarinic receptors to the antagonists on the sinoatrial node are different from those on the atrioventricular node in the heart. PMID- 2600815 TI - Release of endogenous dopamine by stimulation of 5-hydroxytryptamine3 receptors in rat striatum. AB - 5-Hydroxytryptamine (5-HT) caused a persistent, concentration-dependent increase of spontaneous release of endogenous dopamine (DA) from superfused rat striatal slices. 2-Methyl-5-HT, a selective 5-HT3 agonist, mimicked the 5-HT response with a potency only slightly less than that of 5-HT. A highly selective 5-HT3 antagonist, ICS 205-930 [(3-alpha-tropanyl)1H-indole-3-carboxylic acid ester], inhibited the effect of both agonists with a pKB value characteristic of 5-HT3 receptors. 5-HT-evoked DA release was resistant to antagonism by methiothepin and methysergide, antagonists at 5-HT 1-like and 5-HT2 receptors. Neither (2,5 dimethoxy-4-iodophenyl)-2-aminopropane, the selective 5-HT2 receptor agonist, nor 5-carboxamidotryptamine, the selective 5-HT 1-like receptor agonist, altered DA release. The release of DA by 5-HT3 stimulation was Ca++-dependent and partially sensitive to tetrodotoxin. 5-HT and 2-methyl-5-HT also increased K+-evoked DA release. These observations constitute direct, unambiguous evidence that in rat striatum 5-HT3 receptors modulate release of DA. PMID- 2600816 TI - Transport of histone through the blood-brain barrier. AB - The present studies were designed to determine if the endogenous cationic protein, e.g., histone, is capable of penetrating the blood-brain barrier (BBB) in vivo. Calf thymus histone was iodinated with [125I]iodine and was found to be taken up rapidly by isolated bovine brain capillaries used as an in vitro model system of the BBB via a time- and temperature-dependent mechanism. The binding was saturable and a Scatchard plot of the binding data was linear, yielding a KD = 15.2 +/- 2.8 microM and a maximal binding = 7.7 +/- 1.0 nmol/mg of protein. Other polycations such as protamine or polylysine markedly inhibited uptake of [125I] histone, but cationized albumin demonstrated minimal inhibition and cationized immunoglobulin caused no inhibition of bovine brain capillary uptake of [125I]histone. The in vivo brain VD of [125I] histone reached 159 +/- 70 microliters/g by 10 min of carotid arterial perfusion as compared to the 10-min VD for [3H]albumin, 17 +/- 7 microliter/g. Most of this uptake represented sequestration by the vasculature, but approximately 8% of the total histone taken up by brain was found to be transported unmetabolized (based on trichloroacetic acid precipitability of brain supernatant [( 125I]) into brain interstitium. These studies demonstrate that histone is transported through the BBB in vivo via absorptive-mediated transport. Thus, histone is an endogenous protein that is capable of transport through the BBB and may be a potential vector for pharmaceutical delivery through the BBB. PMID- 2600817 TI - Kinetics of drug action in disease states. XXXVII. Effects of acute fluid overload and water deprivation on the hypnotic activity of phenobarbital and the neurotoxicity of theophylline in rats. AB - Fluid overload and dehydration are potentially serious physiologic perturbations. Their effects on the pharmacodynamics of drugs are essentially unknown. This investigation was designed to determine the effects of acute fluid overload or water deprivation on the hypnotic activity of phenobarbital and on the neurotoxicity of theophylline in male Lewis rats. In the first experiment, 5% dextrose in water (D5W) was infused i.v. in an amount equal to 5 or 10% of body weight and phenobarbital was infused immediately thereafter until the onset of loss of righting reflex (LRR). The total infused dose and the serum and cerebrospinal fluid (CSF) concentrations of phenobarbital at that time were significantly lower than in control animals. When phenobarbital was infused about 2.5 hr after D5W, the infused dose and the serum and CSF concentrations of phenobarbital at LRR were normal. When the rats received D5W and an injection of vasopressin, 25 I.U./kg, or vasopressin only, the infused dose and the serum and CSF concentrations of phenobarbital at LRR were significantly lower than in controls despite the 2.5-hr interval between the respective pretreatments and the phenobarbital infusion. Water deprivation for 24 or 48 hr had no significant effect on phenobarbital dose and concentrations at LRR. Intravenous infusion of D5W to 10% of body weight immediately or 2.5 hr before theophylline infusion had no significant effect on the total infused dose and the serum and CSF concentrations of theophylline at onset of maximal seizures. This lack of effect occurred despite appreciable hyponatremia and hypomagnesemia immediately after D5W infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600818 TI - Neuropeptide Y preferentially potentiates responses to adrenergic nerve stimulation by increasing rate of contraction. AB - Neuropeptide Y (NPY) is colocalized with norepinephrine and coreleased from adrenergic nerves. NPY reportedly can influence vascular neuroeffector transmission in both negative and positive directions. Mechanisms by which NPY effects are exerted and their relative contribution may vary between different blood vessels. Therefore, we investigated effects of NPY on adrenergic neurotransmission in ring segments of the rat tail artery by measuring isometric force development and [3H]norepinephrine release. NPY (1-100 nM) potentiated responses to transmural nerve stimulation (3 Hz, six pulses) by more than 300% but produced no direct contractile effects. NPY potentiated responses to longer transmural nerve stimulation trains (30-100 pulses) or to exogenous norepinephrine by only 30%. NPY had no effect on [3H]norepinephrine overflow with either short (six pulses) or long (30 pulses) stimulation trains. Contractile responses to transmural nerve stimulation were completely blocked by prazosin (10(-7) M) both in the absence and presence of NPY. Since the impact of an increased rate of contraction on the contractile response achieved would be greater with short stimulation trains, the effect of NPY on contraction rate was analyzed. NPY increased the rate of contraction to both norepinephrine and transmural nerve stimulation. It is hypothesized that NPY increases the early (phasic) component of the contractile response by preferentially influencing release of intracellular calcium stores. These findings suggest that the effects of NPY will be more profound on phasic rather than sustained patterns of nerve traffic. PMID- 2600819 TI - [3H]CGS 21680, a selective A2 adenosine receptor agonist directly labels A2 receptors in rat brain. AB - Characterization of the adenosine A2 receptor has been limited due to the lack of available ligands which have high affinity and selectivity for this adenosine receptor subtype. In the present study, the binding of a highly A2-selective agonist radioligand, [3H]CGS 21680 (2-[p-(2-carboxyethyl)-phenethylamino]-5'-N ethylcarboxamido adenosine) is described. [3H]CGS 21680 specific binding to rat striatal membranes was saturable, reversible and dependent upon protein concentration. Saturation studies revealed that [3H]CGS 21680 bound with high affinity (Kd = 15.5 nM) and limited capacity (apparent Bmax = 375 fmol/mg of protein) to a single class of recognition sites. Estimates of ligand affinity (16 nM) determined from association and dissociation kinetic experiments were in close agreement with the results from the saturation studies. [3H]CGS 21680 binding was greatest in striatal membranes with negligible specific binding obtained in rat cortical membranes. Adenosine agonists ligands competed for the binding of 5 nM [3H]CGS 21680 to striatal membranes with the following order of activity; CGS 21680 = 5'-N-ethylcarboxamidoadenosine greater than 2 phenylaminoadenosine (CV-1808) = 5'-N-methylcarboxamidoadenosine = 2 chloroadenosine greater than R-phenylisopropyladenosine greater than N6 cyclohexyladenosine greater than N6cyclopentyltheophylline greater than S phenylisopropyladenosine. The nonxanthine adenosine antagonist, CGS 15943A, was the most active compound in inhibiting the binding of [3H]CGS 21680. Other adenosine antagonists inhibited binding in the following order; xanthine amine congener = (1,3-dipropyl-8-(2-amino-4-chloro)phenylxanthine greater than 1,3 dipropyl-8-cyclopentylxanthine greater than 1,3-diethyl-8-phenylxanthine greater than 8-phenyltheophylline greater than 8-cyclopentyltheophylline = xanthine carboxylic acid congener greater than 8-parasulfophenyltheophylline greater than theophylline greater than caffeine. The pharmacological profile of both adenosine agonist and antagonist compounds to compete for the binding of [3H]CGS 21680 was consistent with a selective interaction at the high affinity adenosine A2 receptor. A high positive correlation (r = 0.98, P less than .01) was observed between the pharmacological profile of adenosine ligands to inhibit the binding of [3H]CGS 21680 and the selective binding of [3H]NECA (+50 nM CPA) to high affinity A2 receptors. However, some differences between these assays were found for compounds which have moderate affinity and nonselective actions at both the A1 and A2 adenosine receptor subtypes. Unlike data obtained with nonselective adenosine ligands, the present results indicate that [3H]CGS 21680 directly labels the high affinity A2 receptor in rat brain without the need to block binding activity at the A1 receptor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600820 TI - Effects of prenatal nicotine exposure on development of central and peripheral cholinergic neurotransmitter systems. Evidence for cholinergic trophic influences in developing brain. AB - The development of cholinergic systems in brain regions was evaluated biochemically in developing control rats and rats whose mothers received nicotine via continuous minipump infusion during gestational days 4 to 20. The cerebral cortex displayed a unique maturational pattern of choline acetyltransferase (ChAT) activity and high-affinity synaptosomal [3H]choline uptake capabilities, characterized by increases in the concentration of these components and a postnatal spike of neuronal activity as assessed with the uptake/ChAT ratio; the peak of activity coincided with the time at which neurogenesis declines and synaptogenesis rises. Evaluation of the same markers in midbrain + brainstem indicated rises in uptake which were relatively unselective, primarily reflecting tissue growth and no postnatal peak of uptake/ChAT; cerebellum likewise showed primarily tissue growth-related changes in ChAT rather than increases in its specific concentration. Prenatal exposure to nicotine had a marked adverse effect on developmental patterns of ChAT, uptake and uptake/ChAT only in cerebral cortex, the region previously shown to exhibit major abnormalities caused by this drug and other treatments with cholinomimetic effects. ChAT was unaffected in peripheral projections to the adrenal. Nicotine may thus selectively disrupt central nervous system development by stimulating nicotinic receptors which are present in fetal brain, prematurely eliciting the events ordinarily triggered postnatally by cholinergic projections. PMID- 2600821 TI - Neurochemical effects of amphetamine metabolites on central dopaminergic and serotonergic systems. AB - Intrastriatal administration of the hydroxylated metabolites of amphetamine, p hydroxyamphetamine (p-OHA) or p-hydroxy-norephedrine (p-OHNor), decreased local concentrations of dopamine and serotonin in a dose-dependent manner. Although both compounds reduced concentrations of the metabolites of dopamine, 5 hydroxyindoleacetic acid concentrations were elevated. After systemic treatment with p-OHA, striatal dopamine was also reduced. In contrast, only hypothalamic and hippocampal serotonin stores were altered significantly in rats treated with p-OHA systemically. Neither compound decreased the activities of tryptophan hydroxylase or tyrosine hydroxylase. Because p-OHA is metabolized to p-OHNor via dopamine beta-hydroxylase present in noradrenergic neurons, the direct effects of these compounds on dopaminergic and serotonergic variables can be observed in rats which receive intrastriatal drug treatment. p-OHA and p-OHNor were equally potent in decreasing dopamine concentrations. However, p-OHNor was more potent than p-OHA in decreasing serotonin concentrations. Both compounds more readily depleted dopamine compared to serotonin stores. Complete recovery of p-OHA induced decreases in striatal dopamine occurred within 48 hr of intrastriatal administration and concurrent treatment with the dopamine uptake blocker, amfonelic acid, significantly attenuated the p-OHA-induced effects on dopamine. PMID- 2600822 TI - Antagonism by tricyclic antidepressants of the muscarinic receptors located on the adrenergic nerve endings in rabbit heart atrium. AB - Strips of right atrial tissue obtained from male New Zealand rabbits were incubated in Krebs' buffer containing 10 mu Ci/ml of [3H]norepinephrine at 37 degrees C. After washing for 90 min with Krebs' solution containing 10 microM cocaine and 1 microM yohimbine, 2-min effluents were collected for 96 min. The preparations were stimulated 4 times for 3 min, S1, S2, S3 and S4 (field stimulation: 2 Hz, 1 msec, 60 V), and the tritium content of the samples was measured by scintillation spectrometry. S1 served as a control and at S2-4 oxotremorine dose-response curves were taken expressing the dose-related inhibition of the evoked release of [3H]norepinephrine as percentage of the control. Atropine shifted the dose-response curve to the right in a parallel fashion but the antagonism was noncompetitive in as much as the equilibrium constant was smaller at lower concentrations than at higher one (2.3 and 5.8 nM, respectively). The tricyclic antidepressants also displaced the dose-response curve to the right in a parallel fashion but their inhibitory effects were two orders of magnitude lower and the maximal inhibitory effect was reached at around 5 microM also proving the noncompetitive nature of the antagonism. These results are in good correlation with isolated muscarinic receptor binding studies as well as with the cardiac side-effects of tricyclic antidepressants experienced in the course of clinical administration. PMID- 2600823 TI - Stereoselective sulfation of R,S-4'-hydroxypropranolol by canine hepatic cytosol and partially purified phenolsulfotransferases. AB - The stereoselective formation of 4'-hydroxypropranolol sulfate (HOPS) from racemic 4'-hydroxypropranolol (HOP) has been investigated using canine hepatic cytosol and partially purified phenolsulfotransferases (PSTs). Pseudo first order rate constants, Vmax/Kmapp, were significantly greater (P less than .05) for the formation of R-HOPS by canine hepatic cytosol, S/R-HOPS = 0.72. Moreover, double reciprocal replots for the sulfation of both HOP enantiomers were biphasic, suggesting the presence of multiple PST enzymes. Pentachlorophenol (PCP) inhibited the sulfation of both HOP enantiomers with an IC50 of 244 nM, suggesting that phenol (P) forms of the PST enzymes may be primarily responsible for the cytosolic sulfation. Three distinct PST fractions were partially purified from the cytosol and were found to possess unique stereoselectivities toward HOP. Fraction 1 was most stereoselective, S/R-HOPS = 0.51, but was not inhibited by PCP, suggesting that it is a monoamine (M) form PST. Fraction 3 was the most active fraction and mimicked the cytosol in both stereoselectivity, S/R-HOPS = 0.73 vs. 0.72, and susceptibility to PCP inhibition, IC50 = 93 nM. The S/R-HOPS ratio produced by fraction 2 was 0.63. These data demonstrate the presence of multiple PST enzymes with differing stereoselectivities for the enantiomers of HOP in canine hepatic cytosol. Further studies with homogeneous PST isozymes, ideally from human tissue, and other chiral drugs are needed to define the enzymatic mechanism of this reaction and its role in chiral drug metabolism. PMID- 2600824 TI - [3H]zacopride binding to 5-hydroxytryptamine3 sites on partially purified rabbit enteric neuronal membranes. AB - 5-Hydroxytryptamine3 (5-HT3) receptors are present in both central and peripheral neuronal tissues but radioligand binding studies have thus far been limited to crude membranes from brain and vagus nerve. The present studies describe the isolation and characterization from the rabbit small bowel of neuronal membranes enriched in binding sites for the potent 5-HT3 ligand, [3H]zacopride. The number of specific [3H]zacopride binding sites per milligram of protein was increased 6 fold in a 10,000 to 100,000 x g membrane fraction as compared to the homogenate. [3H]Zacopride bound to these membranes with high specificity (greater than 90%), exhibited high affinity for a homogeneous population of binding sites (Kd = 0.3 nM) and its binding was inhibited competitively by other 5-HT3 compounds with the following rank order of potency: ICS 205-930 greater than GR 38032F greater than or equal to quipazine greater than BRL 24924 approximately MDL 72222 much greater than metoclopramide greater than 2-CH3-5-HT3. On a discontinuous sucrose gradient, specific [3H]zacopride binding was increased an additional 3.5-fold and copurified with three plasma membrane markers. Fractionation on a continuous sucrose gradient demonstrated that specific [3H]zacopride binding was associated with the enteric neuronal plasma membranes. Comparative studies in rabbit vagus nerve also demonstrated a large number (maximum binding = 148 fmol/mg of protein) of high affinity [3H]zacopride binding sites (Kd = 0.4 nM), in membranes that exhibited a density and binding characteristics similar to those from enteric neurons. Thus, membranes enriched in 5-HT3 binding sites can be isolated from both enteric and vagus neurons and [3H]zacopride is a potent ligand useful for characterization of these sites. PMID- 2600825 TI - Effects of paraventricular hypothalamic microinfusions of kainic acid on cardiovascular and renal excretory function in conscious rats. AB - The effects of infusions of kainic acid (KA) into the paraventricular nucleus of the hypothalamus (PVH) on blood pressure (BP), heart rate (HR), baroreflex sensitivity, renal hemodynamics and urinary electrolyte (Na+, K+) excretion were examined in conscious rats. Provocative doses of KA (0.3, 1 and 3 ng/microliters.hr) were infused into the PVH to selectively stimulate neuronal cell bodies, but not fibers of passage. Unilateral PVH infusions of KA (1 ng/microliter.hr) produced excitatory behavior primarily consisting of occasional grooming and increased locomotor activity, and periodic increases in BP and HR. The mean slope of the baroreflex response (delta heart period/delta mean BP; phenylephrine infusion method) curves was decreased by 24% (P less than .01 vs. control) when measured 1 to 1.5 hr after initiation of PVH infusion. The extent of diffusion of [3H]KA (1 ng/microliter.hr) was examined 1 hr after PVH infusion. Radioactivity was detectable at levels above 3 x background 1.6, 2.0 and 3.5 mm, respectively, from the injection site in sagittal, coronal and horizontal planes, indicating fairly extensive distribution patterns. Paraventricular hypothalamic infusions of KA (3 ng/microliters.hr) produced more intense behavioral excitation with slightly greater increases in BP and HR as compared with 1 ng/microliter.hr infusions. Paraventricular hypothalamic infusions of KA (1 and 3 ng/microliters.hr) increased urine flow and urinary Na+ and K+ excretion without affecting urine osmolality, whereas infusions of KA (0.3 ng/microliters.hr) produced no alterations in behavior, BP, HR, renal hemodynamics or renal excretory function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600826 TI - Spontaneous EEG changes during tobacco abstinence and nicotine substitution in human volunteers. AB - Electroencephalographic correlates of tobacco abstinence and nicotine substitution were measured in adult male cigarette smokers in residence on a research ward in two experiments. After ad libitum smoking, seven subjects were deprived of nicotine for 10 days and then resumed smoking. During tobacco abstinence, there were significant decreases in alpha frequency and beta frequency and increases in theta power. These effects were observed as early as 29 hr and in some instances persisted for 7 days. In the second experiment, a group of eight heavy smokers chewed 12 pieces of either placebo or nicotine containing polacrilex gum (2 or 4 mg) per day while deprived of cigarettes. In the placebo condition, electroencephalographic signs were similar to those accompanying tobacco deprivation in the first experiment. Administration of nicotine polacrilex prevented the appearance of these tobacco withdrawal signs. This study provides new information on the time course of certain electrophysiologic components of the tobacco withdrawal syndrome and confirms that the effects are specific to the deprivation of nicotine. The data also suggest that the 4-mg polacrilex was more effective than the 2-mg dose when the results across all measures were considered. PMID- 2600827 TI - Contractile characteristics and innervation ratio of rat soleus motor units. AB - 1. Physiological properties of motor units in the soleus muscle were studied in anaesthetized rats using ventral root splitting to isolate single units. 2. Motor unit types were classified by the same criteria used to classify cat hindlimb motor units into types FR (fast-twitch, fatigue-resistant) and type S (slow twitch, fatigue-resistant). Type FR units were estimated to generate 10% of whole muscle tension and type S 90%. All FR units showed sag in the unfused tetanus at frequencies with interpulse intervals greater than 175% of twitch time to peak, but not at 125% (Burke, Levine, Tsairis & Zajac, 1973). 3. The muscle fibres belonging to twelve single motor units were depleted of glycogen by prolonged stimulation, permitting analysis of their histochemical profiles. Type FR units were found to consist of type IIA muscle fibres and type S units of type I muscle fibres. 4. Direct determinations were made of fibre area, innervation ratio (number of muscle fibres supplied by one motoneurone) and hence specific tension (tetanic tension generated per unit cross-sectional area) of individually identified motor units. Motoneurons were found to innervate between 84 and 178 muscle fibres (mean 110) in type S units and between 126 and 161 fibres in type FR units (mean 142). Fibre areas were larger for type FR units and there was a significant difference in specific tension of the two unit types (type S lower). 5. Indirect estimates of innervation ratio and specific tension were obtained from counts of muscle fibre types, and relative frequencies of motor unit types in the soleus unit pool. Observations agreed well with results of direct measurements. 6. The evidence provided suggests that differences in tension generated by type FR and S units in rat soleus muscle are primarily due to differences in innervation ratio and fibre area, with a small contribution from differences in specific tension. PMID- 2600828 TI - Development of desensitization during repetitive end-plate activity and single end-plate currents in frog muscle. AB - 1. The amplitudes of end-plate currents (EPCs) in short trains of fifteen to seventeen EPCs at 10 Hz were depressed in the presence of 10 microM-proadifen when acetylcholinesterase (AChE) was inhibited. 2. The proadifen-induced EPC depression was voltage-dependent and the effect was more pronounced at negative membrane potentials. 3. In the presence of proadifen, the mean amplitude of miniature end-plate currents (MEPCs) was reduced by 36% 5 s after the EPC train as compared with MEPCs before the train. 4. Without proadifen, but with inhibited AChE, an increase of temperature from 20 to 26 degrees C and elevation of external Ca2+ from 1.8 to 2.5 mM led to EPC amplitude depression in the train, which was also potential-dependent. 5. After AChE inhibition, proadifen (10 microM) progressively shortened MEPC decay without significant reduction of amplitude up to 40 min of exposition. MEPCs were not affected by proadifen when AChE was active. 6. It is concluded that these postsynaptic effects of proadifen can be explained neither by its action on the resting acetylcholine receptors (AChR) nor on open ion channels but are due to its desensitization-promoting action. PMID- 2600829 TI - Calcium-force coupling mechanisms during vasodilator-induced relaxation of ferret aorta. AB - 1. The effects of three vasodilators, nifedipine, hydralazine and forskolin, were determined on isometric force and intracellular ionized calcium concentration ([Ca2+]i) as indicated by aequorin in ferret aorta. Three types of contraction were studied: the intrinsic tone induced by warming from 22 to 37 degrees C; the contraction to the phorbol ester 12-deoxyphorbol-13-isobutyrate-20-acetate (DPBA); and the contraction to potassium depolarization. 2. On warming there was no significant steady-state change in [Ca2+], even though 5.7 +/- 0.7 mN of tone developed. During potassium depolarization, [Ca2+]i rose to a sustained plateau while DPBA caused no significant rise in [Ca2+]i. 3. Nifedipine and hydralazine inhibited intrinsic tone while causing an associated decrease in [Ca2+]i; but in the presence of forskolin, a similar inhibition of tone was accompanied by no significant decrease in [Ca2+]i. 4. Nifedipine and hydralazine prolonged the characteristic lag phase before force development in response to DPBA but did not cause a significant change in contraction amplitude. In contrast, forskolin caused an essentially total inhibition of the contraction. 5. During potassium depolarization, all three vasodilators caused significant decreases in [Ca2+]i coincident with decreases in steady-state force. Calcium-force curves were constructed by plotting the calibrated aequorin light signal against the resulting force. The control calcium-force curve was not shifted by nifedipine or hydralazine but was significantly shifted to the right by forskolin. PMID- 2600830 TI - Changes of intracellular milieu with fatigue or hypoxia depress contraction of skinned rabbit skeletal and cardiac muscle. AB - 1. Maximal calcium-activated force (Fmax) and calcium sensitivity were markedly decreased in detergent-skinned fibres from skeletal and cardiac muscle by solutions that mimicked the total milieu changes associated with fatigue and hypoxia. Further experiments determined the relative contribution of each of the individual changes in milieu. 2. Both Ca2+ sensitivity and Fmax of skeletal and cardiac fibres were decreased with increased [H+] or inorganic phosphate (Pi). These effects were greater in cardiac muscle. 3. Decreasing MgATP over the range observed with fatigue and hypoxia (6.8-4.7 mM) had no effect on Fmax or Ca2+ sensitivity of either muscle type. 4. Decreasing phosphocreatine (PCr: 15-1 mM) increased Fmax but had little effect on Ca2+ sensitivity in both muscle types. In cardiac fibres, the effect on Fmax could be mimicked by inhibition of endogenous creatine kinase. 5. ADP (0.7 mM) increased Fmax and Ca2+ sensitivity, while AMP (0.06 mM) slightly increased Fmax but had no effect on Ca2+ sensitivity of either skeletal or cardiac fibres. 6. Creatine (25 mM) had no significant effect on either Ca2+ sensitivity or Fmax of skeletal and cardiac muscle fibres. At higher levels (50 mM), however, creatine depressed Fmax and slightly altered Ca2+ sensitivity. 7. Thiophosphorylation of myosin P light chains (phosphorylatable light chains of myosin) in rabbit psoas fibres had no effect on Ca2+ sensitivity, yet slightly but significantly increased Fmax under fatigue conditions. 8. Reducing the affinity for ATP hydrolysis (by adding ADP, AMP and creatine) over the range calculated for fatigue/hypoxia (60-45 kJ/mol) produced the enhancement in Fmax expected from added ADP and AMP in cardiac but not skeletal muscle, indicating that changes in affinity influence Fmax of skeletal muscle. Reducing affinity produced little change in Ca2+ sensitivity of skeletal muscle. In contrast, the change produced in cardiac muscle was greater than that expected from addition of ADP and AMP; i.e. decreasing affinity increases calcium sensitivity of the heart. 9. Simple summation of all significant changes expected from each constituent altered by fatigue/hypoxia adequately predicted the observed changes in Fmax and Ca2+ sensitivity in both cardiac and skeletal muscle fibres with but one exception (the change in Ca2+ sensitivity of skeletal muscle at pH 7 was slightly overestimated). PMID- 2600831 TI - Phorbol ester effects on coupling mechanisms during cholinergic contraction of swine tracheal smooth muscle. AB - 1. We studied effects of the phorbol ester, phorbol 12,13-dibutyrate (PDB), on carbachol-induced contractions of swine trachealis muscle. PDB (1-10 microM) markedly inhibited 5.5 microM-carbachol-induced inositol phosphate synthesis allowing us to study (a) whether the membrane potential-independent component of force (pharmacomechanical coupling component) developed in carbachol-stimulated trachealis muscle is dependent on activation of inositol phospholipid metabolism, and (b) whether carbachol-induced membrane depolarization and contraction are altered in muscle where second messenger signals generated by inositol phospholipid metabolism are inhibited and activation of protein kinase C (PKC) is already maximal. 2. Application of PDB (10 microM) to unstimulated trachealis muscle resulted in a small slowly developing contraction associated with a 10 m V membrane depolarization. PDB-evoked contractions were not influenced by Na+ or Cl ion substitutions, or administration of amiloride, all of which inhibited PDB evoked membrane depolarization. 3. Pre-treatment with PDB had no effect on [K+] force, or [K+]-membrane potential relationships, over a range of extracellular [K+] from 40 to 70 mM. Pretreatment with PDB had no effect on extracellular [Ca2+]-force relationships during 40 mM-K+. 4. Carbachol-evoked contractions of muscle treated with PDB became similar to K+ contractions in regard to effects of organic Ca2+ antagonist drugs or decrease in bathing solution [Ca2+]. At low carbachol concentrations, verapamil plus PDB completely inhibited force development. With 5.5 microM-carbachol, over 90% of total carbachol-induced force was inhibited by verapamil, or nifedipine, plus PDB. 5. Control carbachol-evoked contractions were associated with 20-25 mV membrane depolarizations. In PDB treated muscle, carbachol-evoked contraction occurred with a blunted depolarization, i.e. about 5 mV. 6. Force controlled by pharmacomechanical coupling mechanisms operating during maintained carbachol-evoked contractions was inhibited by treatment with PDB. Carbachol-induced force dependent on pharmacomechanical coupling mechanisms could be explained by signals generated via inositol phospholipid metabolism. 7. Electromechanical coupling mechanisms were augmented during carbachol in PDB-treated muscle. This appears to be due primarily to changes in the properties or number of surface membrane voltage gated Ca2+ channels. 8. Data suggest an important role of PKC-mediated phosphorylations for control of both pharmacomechanical coupling mechanisms mediated by activation of inositol phospholipid metabolism and electromechanical coupling mechanisms mediated by effects on operation of surface membrane ion channels. PMID- 2600832 TI - Mechanically evoked responses of afferent fibres innervating the guinea-pig's ureter: an in vitro study. AB - 1. Electrophysiological recordings from ureteric mechanosensitive afferent fibres were performed using an in vitro preparation of the guinea-pig ureter and associated nerves. Single-unit recordings were obtained from small ureteric nerves arising from the inferior mesenteric ganglion, the hypogastric nerve or the pelvic plexus. The fibre composition of these ureteric nerves was also examined by electron microscopy. 2. In two ureteric nerve bundles, which were taken as representative of the maximal and minimal size of nerves used in the electrophysiological recordings, the number of nerve fibres was found to be 417 and 48, respectively. In the bigger nerve 12% of the fibres were small myelinated and the rest unmyelinated. The smaller nerve consisted of unmyelinated fibres only. 3. Electrophysiological recordings were made from sixty-seven mechanosensitive afferent fibres. The conduction velocities (CV) of forty-two of them were determined and all were found to be in the C fibre range (mean CV, 0.4 m/s). Of 119 additional fibres which were not further characterized 112 were C fibres (mean CV, 0.51 m/s) and seven were A delta fibres (mean CV, 3.78 m/s). 4. Mechanosensitive units were classified into two groups according to their ability to respond to contractions of the ureter: (i) U-1 units (9% of all mechanosensitive units) responded to contractions of the ureter and did not show on-going activity or after-discharges to mechanical stimulation. They had low thresholds to intraluminal distension (mean, 8 mmHg) and responded with a short latency to pressure stimuli. (ii) U-2 units (91% of all mechanosensitive units) did not respond to contractions of the ureter, had spontaneous activity between 0 and 2.4 Hz and exhibited after-discharges to mechanical stimuli lasting up to several minutes. They responded after a long latency (greater than 3 s) to distensions in the range of 5-30 mmHg. 5. The level of spontaneous activity and the pressure thresholds of the U-2 units were found to be different depending on whether or not the ureter was perfused intraluminally. Thus U-2 units recorded with intraluminal perfusion had a lower rate of on-going activity and higher threshold to intraluminal distension than U-2 units recorded without intraluminal perfusion. 6. Movement of an intraluminal glass bead under the receptive field of the units evoked strong responses in nine of eleven U-2 units tested as soon as their receptive fields were reached. 7. Our results demonstrate the existence of two classes of mechanosensitive afferent fibres in the guinea-pig ureter.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600833 TI - A novel type of delayed tension reduction observed in rat motor units after intense activity. AB - 1. A delayed reduction of tetanic tension during recovery from fatigue, produced by repeated tetanic contractions, has been found in isolated amphibian muscle fibres (Westerblad & Lannergren, 1986). We have now followed the recovery in a mammalian muscle preparation to see if a similar phenomenon may appear also in mammalian muscles. 2. Single motor units of the rat tibialis anterior muscle were fatigued by 200 ms-80 Hz stimulation trains, initially delivered every 4 s and then at decreasing intervals until tension was depressed to about 30% of the original. 3. After about 10 min of recovery tetanic tension was almost normalized. Tension then decreased in most units to a minimum, which occurred after 30-100 min of recovery. At this stage tension outputs ranged from 6 to 95% of controls. 4. The EMG amplitude was also followed and like tension it was first almost normalized and then depressed. Generally the EMG depression was bigger than the tension loss; the EMG amplitudes were also somewhat reduced in the units not displaying any clear force reduction. 5. Both tetanic tension and EMG amplitude recovered gradually from the depressed state and values similar to controls were eventually reached. 6. In conclusion, we have found a novel type of delayed tension reduction in mammalian muscle during recovery after fatiguing contractions. The exact cause of this reduction is presently unclear, but an important contribution from impaired excitation-contraction coupling is highly plausible. PMID- 2600834 TI - Further evidence for the origin of circulating calcitonin gene-related peptide in the rat. AB - 1. We have attempted to determine the origin of a potent circulating vasodilator, calcitonin gene-related peptide (CGRP), by assessing the effects of administration of capsaicin and colchicine, and of thyroidectomy on plasma levels. Plasma CGRP, neurokinin A and calcitonin levels were measured using highly sensitive and specific radioimmunoassays, and the circulating forms of CGRP characterized by size-exclusion gel and high-performance liquid chromatography. 2. Seven minutes following the intraperitoneal injection of capsaicin (10 mg/kg body weight) plasma CGRP and neurokinin A levels were found to rise by 15- and 4-fold respectively, while there was no change in circulating calcitonin levels. Chromatography revealed that the immunochemical forms of CGRP released into the circulation by capsaicin were similar to those found in normal plasma, which included a peak co-eluting with the intact CGRP molecule. 3. Six hours after the intraperitoneal administration of colchicine (10 mg/kg body weight), CGRP was not detectable in the circulation of 40-day-old rats and plasma levels were significantly lowered in the group of greater than or equal to 200 day-old rats. Chromatography revealed that peaks of circulating immunoreactivity corresponding to monomeric CGRP and its fragments were substantially reduced following colchicine treatment. 4. The magnitude of capsaicin-evoked elevation of plasma CGRP was only marginally (significant at 0.1 greater than P greater than 0.05) reduced by pre-treatment with colchicine. 5. Thyroidectomy alone caused a significant reduction of plasma CGRP levels in greater than or equal to 200-day old rats; a greater reduction was observed when thyroidectomy was combined with colchicine administration. However, when 40-day-old rats were thyroidectomized, there was an unexplained elevation of plasma CGRP levels. 6. The results suggest that while CGRP is normally released into the circulation from nerve terminals, both in young adult (40-day-old) and old (greater than or equal to 200-day-old) animals, a thyroidal origin is obvious only in old rats. PMID- 2600835 TI - Cardio-respiratory responses to cool ambient temperature differ with sleep state in neonatal lambs. AB - 1. Responses to cool ambient temperature were tested with reference to the sleep wakefulness cycle in six chronically instrumented newborn lambs which were exposed to warm (20-25 degrees C) and cool (10-15 degrees C) ambient temperatures (Ta) in fifteen studies. 2. We measured cardio-respiratory variables (cardiac output, heart rate, stroke volume, arteriovenous O2 difference and O2 consumption) together with body temperature (Tb) during behavioural states of quiet wakefulness (QW), quiet sleep (QS) and rapid-eye-movement sleep (REM). 3. In cool Ta, significant increases (P less than 0.05) occurred in cardiac output, O2 uptake and O2 consumption in QW (10 +/- 3%, 23 +/- 4% and 35 +/- 6%, respectively, mean +/- S.E.M.) and QS (12 +/- 3%, 21 +/- 7% and 35 +/- 8%, respectively), but these responses were absent in REM. Increases in heart rate (6 +/- 2%) and stroke volume (6 +/- 3%) were present during QS, but not during REM. 4. In REM, Tb was dependent upon the prevailing Ta, increasing in the warm Ta and tending to decrease in the cool Ta. 5. In cool Ta, REM sleep epochs were shorter and more frequent with no changes in total REM time. These changes were not seen in QS. 6. Thus, the behavioural state determines both the thermogenic and the associated cardio-respiratory responses to cool stress in lambs. The consequences of disrupted thermogenesis during REM sleep include dependence of Tb upon the prevailing ambient temperature, and abbreviation of the REM epoch by arousal, possibly as a defence against falls in Tb in cool Ta. PMID- 2600836 TI - A near-zero membrane potential in transporting corneal endothelial cells of rabbit. AB - 1. When rabbit corneal endothelial cells are impaled with 3 M-KCl-filled microelectrodes (Rt = 20-70 M omega) a stable membrane potential of -28.7 +/- 4.8 mV (mean +/- S.D., n = 400) is measured. 2. Varying the [KCl] of the filling solution causes a change in measured membrane potential; 154 mM gives typically 2 mV, 10 mM typically +37 mV. 3. Variation in membrane potential with different [KCl] cannot be ascribed to tip potential. Double-barrelled microelectrodes containing a different [KCl] in each barrel both give the same membrane potential when inserted into a cell. 4. Microelectrodes filled with a reference liquid ion exchanger (RLIE) give a membrane potential of +2 mV. 5. Impaling a cell with a double-barrelled microelectrode, one barrel containing KCl and the other RLIE, showed that the ion exchanger is not having a toxic effect on the cell and does not affect membrane potential measured by the KCl-filled barrel. 6. We suggest that microelectrodes containing non-isotonic concentrations of KCl generate a significant and artifactual change in membrane potential of corneal endothelial cells caused by the movement of excess KCl (originating from the microelectrode tip) across the plasma membrane where a liquid-junction potential is generated. 7. We further suggest that the physiological membrane potential of corneal endothelial cells is around zero. This could result from a solution of the constant field equation where: 0.9 PNa congruent to PK congruent to 3.2 PCl. PMID- 2600837 TI - Identification of the major membrane currents in freshly dispersed single smooth muscle cells of guinea-pig ureter. AB - 1. The passive and active electrical properties of freshly dispersed single cells of the guinea-pig ureter were investigated using standard patch-clamp techniques. 2. Action potentials, having a rapid rising phase and a prolonged plateau, were recorded on passing depolarizing currents through the patch pipette when 'near normal' physiological gradients were established across the cell membrane (5.9 mM K+, 1.5 mM-Ca2+ in the bath; 126 mM-K+ in the pipette). 3. Under voltage clamp, depolarization to potentials positive of -50 mV (from a holding potential of -70 or -80 mV) triggered a net inward current which reached a peak in 5-10 ms and then slowly inactivated. 4. The averaged membrane current to depolarization to potentials between -30 and 0 mV showed two distinct patterns after the peak of the inward current; the membrane current either moved slowly outward over 400 ms or there was one or more transient outward currents superimposed on the slowly decreasing inward current. Both outward currents were blocked when 5 mM tetraethylammonium (TEA) was added to the bathing solution, resulting in an increased inward current at all potentials. 5. Replacing the extracellular Ca2+ with Co2+ (1.5-5 mM) blocked the inward current and the outward currents to reveal another transient outward current (voltage activated) which activated rapidly to reach a peak within 5 ms and which inactivated exponentially with a time constant of 10 ms. This voltage-activated outward current was inactivated if the membrane was held at -50 mV, but could be reactivated by short hyperpolarizing pre-pulses. The amplitude of this transient current in response to a fixed depolarization (to 0 mV) was half-maximum when the hyperpolarizing pre pulse was to -66 mV. The voltage-activated outward current was reduced in amplitude when the extracellular potassium was raised to 46 mM or upon exposure to 1 mM-4-aminopyridine (4-AP), but was not affected by 5 mM-TEA. 6. Replacing K+ in the pipette and bathing solution with caesium (Cs) blocked all outward currents, revealing the time course and voltage dependence of the inward current, which could be carried by Ca2+ or Ba2+ with little effect on its rate of inactivation. 7. It was concluded that the inward current recorded in single ureter cells was due to the flow of current through voltage-activated Ca2+ channels. The TEA-sensitive outward currents, whether transient or slowly activating, are presumably K+ channels activated by Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600839 TI - Mechanical influences on long-lasting human muscle fatigue and delayed-onset pain. AB - 1. The influence of three mechanical factors, force, muscle length and passive lengthening, on long-lasting changes in voluntary force generation, the force:frequency relationship and the development of tenderness has been studied in healthy human skeletal muscle. The elbow flexors were used in all studies. The effect of muscle length was also investigated in the quadriceps and adductor pollicis muscles. Eighty maximal voluntary contractions (MVCs) were performed: one contraction, lasting approximately 2 s, every 15 s. The MVC and force:frequency relationships were measured before and immediately after the exercise and, together with an assessment of tenderness, at 24 h intervals thereafter. 2. In a series of experiments designed to investigate the effects of force, eccentric (lengthening) contractions were found to cause greater fatique and delayed-onset muscle pain than either isometric or concentric (shortening) contractions. There were, however, no substantial differences between the effects of isometric and concentric contractions. Changes in MVC took 24-48 h to return to normal while the low-frequency fatigue required 3-4 days to recover. 3. Passive lengthening with a comparable number of movements over the full range had no effect on the force generation of the muscle, nor did it cause any muscle pain. 4. In the series of experiments designed to investigate the effects of length, isometric MVCs were performed at either short or long length and the muscles subsequently tested at an intermediate length. The contractions at long length resulted in greater low-frequency fatigue and pain, despite the fact that they generated less force than those at the short length. 5. The results demonstrate that there is no simple relationship between the force generated during exercise and the development of long-lasting muscle fatigue and pain. Furthermore, there is a length-dependent component in the generation of low frequency fatigue and muscle pain. PMID- 2600838 TI - A voltage-dependent outward current with fast kinetics in single smooth muscle cells isolated from rabbit portal vein. AB - 1. Single smooth muscle cells were isolated enzymatically from the rabbit portal vein. They were voltage-clamped at room temperature using the whole-cell configuration of the patch-clamp technique. 2. When cells were bathed in physiological salt solution, depolarization from a holding potential of -70 mV elicited a time-dependent outward current which reached a maximum within 0.2-0.5 s, but when a more negative holding potential was used, an additional outward current could be activated. The current (Ifo) developed rapidly, was transient and seemed to be carried by potassium ions (K+). 3. The steady-state inactivation plot for Ifo was steeply voltage-dependent between -90 and -60 mV, current being 50% inactivated at -78 mV. The activation threshold was around -65 mV. The activation and inactivation kinetics were fast and voltage-dependent. When the test potential was -35 mV, peak current occurred after about 15 ms and the decay was complete within 250 ms. Recovery from inactivation was maximal after 1 s at 100 mV but was about five times slower at -70 mV. 4. The outward current Ifo was blocked completely by 4-aminopyridine (5 mM) or phencyclidine (0.1 mM), but was insensitive to tetraethylammonium ions (32 mM), apamin (0.1 microM), charybdotoxin from the venom of Leiurus quinquestriatus (0.1 microM), toxin-I from the venom of Dendroaspis polylepis (1 microM) or the putative K+ channel opener, cromakalim (10 microM). 5. The steady-state inactivation range and activation threshold, kinetics of activation and inactivation all showed a marked dependence on the concentration of divalent cations in the bathing solution. This effect was consistent with the hypothesis that Ifo was affected by membrane surface potential. The current did not seem to be Ca2+-activated. 6. Ifo closely resembled the A-current which has been described previously in neurones but not in smooth muscle. PMID- 2600840 TI - Analysis of factors that contribute to cardiovascular changes induced in the cat by graded levels of systemic hypoxia. AB - 1. In cats anaesthetized with Saffan, which does not block afferent activation of the brain stem defence areas, we have analysed the cardiovascular changes induced by 3 min periods of graded systemic hypoxia (fraction of O2 in inspirate, Fi,O2, 0.15, 0.12, 0.08, 0.06). 2. At light levels of Saffan anaesthesia, hypoxia (particularly Fi, O2 0.08 and 0.06) or selective stimulation of carotid chemoreceptors evoked the pattern of tachycardia, decrease in renal and mesenteric vascular conductance (RVC, MVC), but increase in femoral vascular conductance (FVC) which is characteristic of the alerting-defence response. This supports our view that activation of the defence areas is an integral part of the response to systemic hypoxia. 3. Hypoxia also induced an increase in frequency of augmented breaths which was graded with the level of hypoxia: 0.6 min-1 at Fi, O2 0.21 to 1.1 min-1 at Fi, O2 0.06; in some cats each of these was accompanied by a transient fall in arterial pressure (ABP) and increase in FVC. It is proposed that these responses were all part of a reflex elicited by lung irritant receptors and facilitated by peripheral chemoreceptors. However, their low rate of occurrence and the liability of the vasodilatation suggests they do not make major contributions to the overall response. 4. The above short-lasting responses were superimposed upon gradual changes whose magnitudes were graded with the level of hypoxia: hyperventilation, slight tachycardia, but bradycardia at Fi, O2 0.6, small increases in ABP, FVC and MVC allowing femoral and mesenteric blood flow to increase, but decreases in RVC which maintained renal blood flow constant. 5. Vagotomy had no significant effect on these changes. Further, hyperinflation of the lungs with pressures of 10 mmHg evoked the Breuer-Hering reflex but had no noticeable cardiovascular effect. It is proposed that, in the cat, reflex tachycardia and vasodilatation elicited by lung stretch receptors play no significant part in the response to hypoxia. 6. By contrast, after pneumothorax, with ventilation and thereby arterial PCO2 (Pa, CO2) maintained constant, graded hypoxia produced graded bradycardia, decrease in MVC and RVC and no change in FVC. Taken together, these results suggest that in the spontaneously breathing cat, the response to hypoxia is dominated by the effects of hypocapnia secondary to hyperventilation, which by inhibiting peripheral and central chemoreceptor activity effectively counteracts the primary bradycardia and peripheral vasoconstriction elicited by hypoxic stimulation of peripheral chemoreceptors. 7. These proposals are compared with those drawn for other species. PMID- 2600841 TI - Monosynaptic EPSPs in cat lumbosacral motoneurones from group Ia afferents and fibres descending in the spinal cord. AB - 1. Excitatory postsynaptic potentials (EPSPs) were elicited in lumbosacral motoneurones of pentobarbitone-anaesthetized cats by stimulating the ventral quadrants (VQ) of the thoracic spinal cord. These EPSPs were compared with monosynaptic EPSPs from small numbers of group Ia afferents, obtained by stimulating hindlimb muscle nerves with most of the dorsal roots severed. 2. EPSPs with average peak amplitude less than 1 mV were selected for fluctuation analysis. Three out of fourteen (21%) VQ EPSPs with peak voltage less than 150 mu V fluctuated in amplitude from trial to trial no more than could be accounted for by the background intracellular noise. Similarly, nine out of thirty-nine (23%) Ia EPSPs smaller than 150 mu V fluctuated to a comparable extent as the noise. These results are consistent with the view that there is little variation in the postsynaptic signal produced by an individual transmitter release event. 3. Of the EPSPs which did fluctuate more than the background noise, maximum likelihood estimates were obtained for the fluctuation patterns of ten VQ and fourteen Ia EPSPs. This was achieved by assuming that synaptic signals sum linearly with noise, but without constraining the results to conform to a statistical description of transmitter release. The fluctuation of both VQ and Ia EPSPs was made up of discrete amplitudes separated by roughly equal increments, in accordance with the quantal hypothesis of synaptic transmission. 4. Fluctuation patterns were obtained simultaneously for VQ and Ia EPSPs in seven motoneurones. The amplitudes of the quanta, defined as the mean increments between discrete amplitudes, were correlated (r = 0.90), suggesting common postsynaptic mechanisms. 5. For most EPSPs the time course of the voltage transient could be used to estimate the electrical distance from the soma at which the synaptic current was injected. There was a comparable distribution for VQ and Ia EPSPs. For those in which a quantal analysis was performed (nine VQ and eleven Ia), quantal size measured at the soma appeared to be independent of the deduced site of origin. 6. The results indicate no qualitative or quantitative differences in the behaviour of VQ and Ia EPSPs. PMID- 2600842 TI - Giant miniature end-plate potentials at the untreated and emetine-treated frog neuromuscular junction. AB - 1. Intracellular recordings from the cutaneous pectoris muscle fibres of the frog showed that giant miniature end-plate potentials (gMEPPs) occurred in untreated preparations. Emetine (10 microM), after a 15-20 min delay, increased the frequency of gMEPPs. In both cases gMEPPs disappeared in the presence of (+) tubocurarine. 2. There was no correlation between the frequency of gMEPPs and the frequency of normal MEPPs (nMEPPs) in untreated or emetine-treated fibres. 3. Tetraphenylborate (TPB, 50 microM) applied to muscles pre-treated with emetine caused the frequency and amplitude of both nMEPPs and gMEPPs to decrease gradually. All MEPPs disappeared in about 10 min. 4. Chloride permeability was modified by changing the pH of the Ringer solution. Changing the pH from 7.2 to 8.2 or 6.2, which in both cases caused marked increases in nMEPP frequency, had no significant effect on gMEPP frequency in untreated muscles. 5. Decreasing the pH from 7.2 to 6.2 blocked the ability of emetine to increase gMEPP frequency. Increasing the pH from 7.2 to 8.2 had no significant effect on emetine ability to increase gMEPP frequency. 6. Treatment with the Cl- channel blocker SITS (0.5 mM) had no effect on gMEPPs in untreated muscle or on the ability of emetine to increase the frequency of these potentials. 7. The Ca2+ sensitivity of gMEPPs in untreated or emetine-treated muscles was tested by treatments which are known to alter intracellular Ca2+. Raising extracellular Ca2+ (10 mM), treatment with Mn2+ (10 mM), Mg2+ (10 mM), K+ (7.5 mM), hypotonic solution, ouabain (0.2 mM) or ethanol (0.5 M), although causing profound changes in nMEPP frequency had no significant effect on gMEPP frequency in untreated fibres or on the ability of emetine to increase gMEPP frequency. 8. It is concluded that at the frog neuromuscular junction generation of the normally occurring or emetine-induced gMEPPs is independent of Ca2+ and does not seem to be influenced by changing membrane C1- permeability. PMID- 2600843 TI - Receptive fields and in-field afferent inhibition of neurones in the cat's lateral cervical nucleus. AB - 1. Extracellular microelectrode recordings were made from projection neurones of the lateral cervical nucleus (LCN) in cats anaesthetized with chloralose and paralysed with gallamine triethiodide. 2. The receptive fields of eight-five units were analysed. Most units had excitatory receptive fields similar in size and shape to those of spinocervical tract (SCT) cells. A few (14%) had either very large fields or 'stocking-like' fields. The majority of the LCN neurones (fifty-five, 65%) were excited by hair movement and, in addition, by noxious mechanical stimulation within the skin area responding to hair movement. Twenty five units (29%) were excited by hair movement alone. For seven of these twenty five neurones, noxious mechanical stimulation within the excitatory receptive field produced inhibition of the background discharge. One unit was excited by noxious mechanical stimulation and for the remaining four units no receptive field could be found. In six units inhibitory receptive fields outside the excitatory field were found. 3. Air-jet stimuli were used to define the excitatory profiles of the units' receptive fields to hair movement. In general, receptive fields had single regions of greatest sensitivity usually at or near the centre of the field, where that was oval in shape, with the sensitivity declining towards the field's circumference. In some units with very large fields that included parts of one or two limbs and the trunk there could be more than one highly sensitive region. 4. Pairs of air-jet stimuli were used to investigate in-field afferent inhibition in LCN cells. One jet was used to condition the responses to another jet located at a different position within the excitatory receptive field and occurring 200 ms later. Sixteen units were tested and significant in-field inhibition was observed in all sixteen. 5. The in-field afferent inhibition was organized spatially in the sense that inhibition was generally strongest when the conditioning and testing stimuli were close together and became weaker as they were moved apart. The afferent inhibition was not simply a function of the response produced by the conditioning stimulus. Furthermore, increasing the strength of the stimuli did not in general lead to larger areas from which the inhibition could be produced. The inhibitory areas defined in these experiments were generally less than 120 mm in length in units with receptive fields much longer than 100 mm.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600844 TI - Enkephalinergic inhibition in parasympathetic ganglia of the urinary bladder of the cat. AB - 1. Repetitive stimulation (10-20 Hz, 0.5-5 s duration) of the preganglionic nerves to ganglia on the surface of the urinary bladder of the cat produced a prolonged inhibition (duration, 30-65 s) of the postganglionic action potentials, elicited by low-frequency stimulation (0.25-1 Hz) of another preganglionic nerve to the same ganglion. 2. Intra-arterial administration of naloxone, an opiate antagonist (20-50 micrograms/kg), reduced the magnitude and duration of this heterosynaptic inhibition and also blocked the depression of ganglionic transmission elicited by the intra-arterial administration of leucine-enkephalin (0.1-10 micrograms/kg). 3. Naloxone did not alter adrenergic inhibition elicited by repetitive stimulation of the hypogastric nerve or exogenous noradrenaline. Naloxone did not alter the postganglionic firing elicited by single stimuli or trains of low-frequency (1-3 Hz) stimuli to the preganglionic nerves. 4. Heterosynaptic inhibition was not altered by the administration of antagonists for alpha-adrenergic (dihydroergotamine, prazosin, yohimbine), muscarinic (atropine), purinergic (theophylline) or GABAergic (picrotoxin) receptors. 5. A delta-selective opiate receptor agonist, DSLET (D-Ser2-leucine-enkephalin-Thr), inhibited parasympathetic ganglionic transmission in low doses (mean threshold dose, 0.02 microgram/kg, I.A.), whereas a mu-opiate receptor agonist, morphine sulphate, produced only a small depression in larger doses (mean threshold dose, 100 micrograms/kg, I.A.). Ethylketocyclazocine, which has an affinity for kappa receptors did not alter transmission in relatively large doses (1 mg/kg, I.A.). 6. These findings coupled with previous immunocytochemical demonstrations of leucine-enkephalin-like immunoreactivity in preganglionic nerve terminals in bladder ganglia suggest that opioid peptides released endogenously from preganglionic nerves are involved in delta-receptor-mediated inhibitory mechanisms at cholinergic synapses in bladder ganglia. PMID- 2600845 TI - Triple-barrel structure of inwardly rectifying K+ channels revealed by Cs+ and Rb+ block in guinea-pig heart cells. AB - 1. The hypothesis that the inwardly rectifying K+ channel consists of a triple barrel structure was investigated. Inward currents were recorded under the blocking effects of external Cs+ or Rb+ in the cell-attached configuration of the patch-clamp technique using single ventricular cells enzymatically isolated from guinea-pig hearts. 2. Cs+ (10-100 microM) or Rb+ (20-100 microM) added to the 150 mM-K+ pipette solution induced rapid open-blocked transitions in the inward open channel currents. In about 20% of experiments the inward current showed two intermediate current levels equally spaced between the unit amplitude and the zero-conductance level. The current fluctuated between these four levels. In the remaining experiments no obvious sublevels were observed except spontaneous ones, whose amplitudes were not always equal to one-third or two-thirds of the unit amplitude. 3. In experiments showing sublevels, the probability that the open channel current stayed at each level was measured at various concentrations of blockers and membrane potentials. In both Cs+ and Rb+ block, the distribution of the current levels showed reasonable agreement with the binomial theorem. This finding suggests that the inwardly rectifying K+ channel is composed of three equally conductive subunits and each subunit is independently blocked by Cs+ or Rb+. 4. The dwell-time histogram in each substate was well fitted with a single exponential function. On the assumption of the binomial model, the blocking (mu) and unblocking (lambda) rate for Cs+ and Rb+ were calculated. The value of mu was linearly proportional to the concentration of the blocking ion at a given membrane potential and increased with hyperpolarization (e-fold increase with a change of -43.5 mV in the Cs+ block). lambda was almost independent of the concentration of the blocking ion and less dependent on the membrane potential than mu. 5. The open and blocked times were calculated in experiments showing no clear sublevels. The mean open time was almost equal to the mean dwell time at the full open level in experiments showing sublevels under the same conditions. On the other hand, the mean blocked time was about two or three times longer than the mean dwell time at the zero-conductance level measured in experiments with sublevels. These results may suggest that the instant one of the three subunits is plugged by blocking ions, the remaining two subunits are closed by unknown mechanisms. 6. Our results support the hypothesis that the cardiac inwardly rectifying K+ channel is composed of three equally conductive subunits. PMID- 2600846 TI - Effects of fatigue and reduced intracellular pH on segment dynamics in 'isometric' relaxation of frog muscle fibres. AB - 1. Longitudinal movements of marked segments of single fibres from the anterior tibialis muscle were recorded during tetanus and relaxation under isometric (fixed-end) conditions. 2. During relaxation, shortening and lengthening of different segments occurred simultaneously, starting at about the same time as the end of the linear fall of force (shoulder on the force record). 3. Variations in intracellular pH, measured with pH-sensitive microelectrodes, along the length of fibres were not statistically significant, and are unlikely to be responsible for the non-uniform behaviour of different segments. 4. As expected from earlier studies, both fatigue (produced by increasing tetanus duration or decreasing the time between tetani) and intracellular acidification (produced by raised extracellular CO2), reduced the tetanus force and prolonged the linear phase of force decline in relaxation. Each treatment delayed the start and markedly reduced the amount of segment movement in relaxation. 5. Fatigue and intracellular acidification have a smaller effect on force during stretching than on force produced under isometric conditions. This may contribute to making the segments behave in a more uniform way during relaxation under these conditions. 6. Changes in the Ca2+ uptake mechanisms are also discussed as possible causes for the changes in segment behaviour in relaxation. PMID- 2600847 TI - Determination of ionic permeability coefficients of the plasma membrane of Xenopus laevis oocytes under voltage clamp. AB - 1. A method of estimating absolute ionic permeability coefficients which does not depend on the use of impermeant substitutes is reported. 2. The method is based on a pump leak model of the Xenopus laevis oocyte membrane. The procedure consists of measuring, in the same experiment, the pump current and the currents generated under voltage clamp by the partial substitution of one or two ions at a time. For each experimental condition, the measured currents are substituted in a Goldman-Hodgkin-Katz type equation with two unknowns (the permeability coefficients). The set of equations thus generated enables the computation of all the ionic permeability coefficients. 3. The Xenopus oocyte membrane (stages IV and V, Dumont, 1972) has been found to be permeable to conventional ion substitutes such as N-methyl-D-glucamine (NMG), sulphate, isethionate and gluconate. 4. The values for sodium, potassium and chloride permeability coefficients obtained from sixty-eight pooled experiments were, respectively, 5.44, 17.41 and 1.49 x 10(-8) cm s-1. 5. The diffusional currents for sodium, potassium and chloride computed from the experiments referred to above were, respectively, -1.16, 0.69 and -0.038 microA cm-2. 6. A stoichiometry of the Na+ K+ pump exchange of 3/1.8 was computed. 7. The intracellular concentrations of sodium, potassium and chloride ions, as determined by ion-selective microelectrodes, were, respectively, 10.1 +/- 0.66 mM (n = 12), 109.5 +/- 3.3 mM (n = 13) and 37.7 +/- 1.18 mM (n = 19), corresponding to equilibrium potentials of 61, -95 and -28 mV. 8. Since chloride is not at equilibrium across the membrane, we propose that there is an inward uphill Cl- transport. PMID- 2600848 TI - Synchronization of motor unit firing during different respiratory and postural tasks in human sternocleidomastoid muscle. AB - 1. Motor unit firing has been studied in human sternocleidomastoid muscle. 2. Two needle electrodes were inserted into the muscle and the activity of pairs of motor units recorded during (a) reflex hypercapnic obstructed breathing, (b) eucapnic voluntary copying of (a) against the same inspiratory resistance and (c) voluntary copying of (a) without any resistance, accompanied by isometric neck rotation. 3. Cross-correlation histograms of the firing of unit pairs showed a clear central peak, indicative of synchronization. The mean duration of the peak during voluntary breathing was 25 ms (range 9-40 ms). There was no difference in duration of synchronization during the different tasks. 4. For the duration of the synchronization peak, the mean strength of synchronization expressed as the number of concomitant discharges of the two units as a proportion of the total number of discharges was 0.026 (range 0.011-0.058) for reflex hypercapnic obstructed breathing. For the same unit pairs the strength of synchronization for isometric neck rotation was the same as that during reflex hypercapnic breathing but for voluntary obstructed breathing it was, on average, threefold greater. 5. In three out of twenty-two motor units studied, 'discharge' occurred with an interval of less than 10 ms ('doublet' firing) at the onset of each inspiration during both types of obstructed breathing; this was rarely observed during neck rotation. 6. The results are interpreted in terms of different synaptic drives to the motor units during the three different tasks. PMID- 2600849 TI - Size and remoteness: two relatively independent parameters of dendrites, as studied for spinal motoneurones of the cat. AB - 1. The spatial extent of motoneuronal dendrites was analysed using data from the fifty-two dendritic trees of four completely reconstructed cat motoneurones that had been labelled with intracellularly injected horseradish peroxidase. The cells belonged to m. triceps surae, and their physiological properties covered much of the known range for this muscle. 2. The percentage of total dendritic area extending beyond a radial somatofugal distance of 750 microns (PA750) was selected as an index of 'dendritic remoteness'. 3. The value of our standard remoteness index PA750 was well correlated with a number of other possible remoteness measures, such as the percentage of total dendritic area beyond 500 or 1000 microns or the percentage of cumulative dendritic length beyond 750 or 1000 microns. 4. Most of the dendritic parameters could be classified as belonging either to a cluster of remoteness-related properties or to a cluster of size related properties. Remoteness-related properties were significantly correlated with PA750 but not with stem diameter. Size-related properties were significantly correlated with stem diameter but not with the remoteness index PA750. The remoteness-related properties included the mean somatofugal distance to branch points, the mean and maximum distance to terminal ending and, somewhat less distinctly, the mean length of terminal branches. The size-related properties included the total dendritic area, the cumulative dendritic length, and the total number of branch points and terminal endings. 5. The extent of area expansion at branch points and the overall extent of tapering were not systematically related to differences in remoteness. 6. The relative degree of remoteness was greater for medial than for lateral dendrites. 7. Even in the present limited sample of cells, there were marked and systematic differences between different neurones with respect to the relative remoteness of their dendrites. The slowest and most high-resistance motoneurone was the one with the most remote dendrites. On the whole there was, however, a considerable degree of independence between the variation in dendritic remoteness and the variation in physiologically determined properties (axonal conduction velocity, input resistance, after hyperpolarization). 8. In the discussion it is suggested that differences in dendritic remoteness might lead to a selectivity between the various members of a given motoneurone pool with respect to their reception of topographically distributed systems of synapses. It is proposed that such differences might be of interest in relation to, for instance, the organization of innervation to motoneurones belonging to different task groups within the same muscle. PMID- 2600850 TI - Dendrites of cat's spinal motoneurones: relationship between stem diameter and predicted input conductance. AB - 1. The electroanatomy of motoneuronal dendrites was analysed using data from fifty-two dendritic trees of four completely reconstructed cat spinal motoneurones that had been labelled with intracellularly injected horseradish peroxidase. The cells belonged to m. triceps surae, and their physiological properties covered much of the known range for this muscle. 2. For each dendritic tree, the input conductance, as seen from the soma, was calculated by the method of Rall (1959), using anatomical measurements of the length and diameter of all branches and different assumed values for dendritic membrane resistivity. 3. There was a strong positive correlation between dendritic stem diameter and the calculated dendritic input conductance. Dendritic input conductance was approximately equal to a constant x (stem diameter)3/2 x (dendritic membrane resistivity)-0.76. 4. The relationship between dendritic stem diameter and computed input conductance was equal to that of Rall's equivalent-cylinder model of a dendritic tree. However, from a number of other points of view, the properties of the reconstructed dendrites differed from those of the model: (a) at branch points, the sum sigma(daughter diameters 3/2) was, on average, 19% greater than the 3/2 power of the parent diameter; (b) dendritic branches often showed a significant amount of tapering, and the mean overall degree of diameter decrease per branch was about 12%; (c) the termination of dendritic branches occurred at widely different distances from the soma within single dendritic trees (true for anatomical as well as for computed electrotonic distances). 5. When used in conjunction with previously published measurements of motoneuronal input resistance and proximal anatomy (Kernell & Zwaagstra, 1981), the present results gave further support to the conclusion that differences in membrane resistivity are of great importance for differences in motoneuronal input resistance. Furthermore, this conclusion was also confirmed by direct observation of the properties of the present four motoneurones: irrespective of the assumed ratio between somatic and dendritic membrane resistivity, there was a statistically significant positive correlation between the measured neuronal input resistance and the required membrane resistivity of soma and dendrites. PMID- 2600851 TI - Systemic and forearm vascular resistance changes after upright bicycle exercise in man. AB - 1. Blood pressure, cardiac function and forearm blood flow following voluntary maximal upright bicycle exercise were studied in thirteen normal volunteers in a cross-over design against a control day. 2. After exercise there was a short lived (5-10 min) increase in systolic blood pressure, peak aortic blood velocity and aortic acceleration suggesting a persistence of the positive inotropic influence of exercise. 3. Systemic vasodilation, which was seen immediately exercise stopped, lasted at least 60 min. This was associated with a reduction in diastolic blood pressure for the whole hour. After 30 min systolic blood pressure was also reduced. Heart rate and cardiac output were still significantly elevated and systemic vascular resistance still reduced at 60 min post-exercise. 4. A non exercising limb vascular bed (forearm) showed a marked vasodilation for 1 h after predominately leg exercise indicating the presence of a vasodilatory influence affecting vascular beds other than the exercising muscle groups. PMID- 2600852 TI - The effect of stimulation of the atrial receptors on plasma cortisol level in the dog. AB - 1. Experiments were performed in dogs anaesthetized with alpha-chloralose to determine whether stimulation of atrial receptors reflexly results in a consistent change in plasma cortisol levels. Either a large balloon in the lumen of the left atrium or small balloons positioned at the upper and middle pulmonary vein-atrial junctions and atrial appendage were distended. Plasma samples obtained from these dogs during control periods and during periods of stimulation were assayed for plasma cortisol level. 2. Initially, stimulation of left atrial receptors by either large or small balloon distension was shown consistently to cause the responses of an increase in urine flow and a decrease in plasma cortisol level. The responses were greater during stimulation using the large balloon than the small balloons. 3. The afferent limb of the responses was shown to involve the vagal nerves. Cooling of the cervical vagosympathetic nerve trunks to 9 degrees C abolished the responses to balloon distension of an increase in urine flow and decrease in the level of plasma cortisol. 4. The efferent limb of the cortisol response was shown to require the pituitary gland. Hypophysectomy abolished the response of a decrease in plasma cortisol level, but not the diuretic response. 5. It was shown that stimulation of left atrial receptors causes a reflex decrease in plasma cortisol level, the afferent limb of which involved vagal nerves and the efferent limb of which depended on the pituitary gland. PMID- 2600853 TI - Multiple blocking mechanisms of ATP-sensitive potassium channels of frog skeletal muscle by tetraethylammonium ions. AB - 1. Patch-clamp methods were used to study the action of tetraethylammonium ions (TEA+) and other quaternary ammonium ions on adenosine-5'-triphosphate (ATP) sensitive K+ channels in sarcolemmal vesicles from frog skeletal muscle. The blocking ions were applied either to the external or the internal surface of the membrane patch. 2. External TEA+ caused a very fast block, so that the amplitude of single-channel currents was reduced. Open-channel variance was decreased. The block was 1:1, with a dissociation constant (Kd) of 6-7 mM. We could detect no voltage dependence of Kd. 3. External TEA+ prolonged open times in a manner consistent with the channel being unable to close when blocked by TEA+. 4. TEA+ also blocked when applied to the internal side of the membrane. This block showed two components with different kinetics and different affinities. The slow block chopped up openings into much briefer events and had a Kd of about 1.4 mM at -3 mV. The fast block reduced the amplitude of unitary currents and was of lower affinity, with Kd around 26 mM. 5. The slow block by internal TEA+ was markedly voltage dependent, the Kd decreasing e-fold for a 37 mV depolarization. Both the association and dissociation rates were dependent on voltage. In contrast, the fast block by internal TEA+ appeared virtually independent of voltage. 6. The effects of internally applied tetramethylammonium (TMA+) and tetrapentylammonium (TPA+) ions were also investigated. Internal TMA+ produced a flickery block while the block by internal TPA+ was similar to that caused by TEA+, although TPA+ was about 10 times more effective. 7. Our results suggest that the channel has three binding sites for TEA+, one of which is accessible from the outside of the membrane. Only one of the internal sites is located so as to experience a substantial fraction of the membrane voltage field. PMID- 2600854 TI - The mechanism of early contractile failure of isolated rat ventricular myocytes subjected to complete metabolic inhibition. AB - 1. Twitch shortening of isolated rat ventricular myocytes was measured on exposure to complete metabolic blockade (2 mM-cyanide in the presence of 10 mM-2 deoxyglucose). Under these conditions twitch shortening declines to undetectable levels over 1-15 min. This 'early' contractile failure is followed by the development of a maintained contracture. 2. Contractures induced by caffeine (20 mM) were similar in amplitude before and after 'early' contractile failure. This result suggests that 'early' contractile failure is not due to depletion of Ca2+ from the sarcoplasmic reticulum. 3. The action potential shortened as the twitch magnitude declined during 'early' contractile failure, raising the possibility of a causal link. Voltage-clamp experiments show that an enormous increase in K+ conductance (greater than 20-fold) occurs during the period of 'early' contractile failure, and presumably underlies the action potential shortening. 4. If the K+ conductance changes are inhibited by replacement of intracellular K+ with N-methyl glucosamine and inclusion of 2 mM-tolbutamide in intra- and extracellular solutions, good voltage control can be achieved. Under these conditions, 'early' contractile failure did not occur on exposure to complete metabolic blockade and neither Ca2+ current nor the twitch were completely abolished until a maintained contracture had begun to occur. 5. Injection of ATP following 'early' contractile failure could partially restore the twitch and prolong the foreshortened action potential. 6. These results are consistent with the hypothesis that 'early' contractile failure occurring under non-voltage clamped conditions is due principally to failure of activation of the Ca2+ current because of the shortening of the action potential. Although a decline in the availability of Ca2+ current also occurs, action potential shortening results mainly from increased conductance through ATP-sensitive K+ channels which are activated by a fall of intracellular [ATP]. Contractile failure arises not because of a primary alteration, or defect, in the coupling of excitation to contraction, but because the cell membrane is effectively clamped at a potential close to the K+ equilibrium potential. PMID- 2600855 TI - The influence of changes in discharge frequency of corticospinal neurones on hand muscles in the monkey. AB - 1. The possibility that the discharge pattern of monkey corticomotoneuronal cells influences the degree to which they facilitate their target hand muscles was tested by compiling spike-triggered averages of EMG recorded from these muscles. 2. Records were made from area 4 corticomotoneuronal cells in three conscious macaque monkeys while they performed a precision grip between index finger and thumb. Simultaneous EMG recordings were made from up to six different intrinsic hand muscles. Twenty cells which produced clear post-spike facilitation of one or more muscles were selected for further analysis. 3. Spikes recorded from these cells were grouped according to the occurrence of a previous spike in the periods 0-10 ms, 10-20 ms, and so on up to 60-70 ms before the trigger spike. The post spike period in which no additional spikes were allowed to fall was kept at either 12.5 or 25 ms. 4. Spikes selected in this way produced a transient facilitation of their target muscle EMG activity. The peak amplitude of this facilitation was normalized as a percentage of modulation of the background EMG level. The background level was determined from a period in the average to which the cell could not have contributed, because of the post-trigger spike interval. We verified that the percentage of modulation was not influenced by the overall level of EMG activity, since, for a given interval, the modulation was the same whether the relevant spikes were selected during periods of high- or low-level EMG activity. 5. The relative amplitude of the post-spike facilitation (i.e. the percentage of modulation) showed marked variation with interspike interval. A full analysis was completed for seventeen neurones. Spikes with the shortest intervals (less than 10 ms) usually produced the strongest effects, and evidence is presented that this was due to temporal summation and facilitation at the corticomotoneuronal synapse. Mid-range intervals (10-40 ms) were generally far less effective, although they constituted the highest proportion of cell activity. 6. A striking finding was the strong facilitation generated by the longer interspike intervals (40-70 ms). Although the absolute size of this post spike effect was much smaller than that of the shortest intervals, its percentage of modulation was similar. It is suggested that this enhanced facilitation results from a combination of lower frequency discharge among the active motoneurones, and increased synchrony in the corticomotoneuronal input to them. 7. All of the above results were confirmed by examining cross-correlations between single corticomotoneuronal cells and single motor units in their target muscle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600856 TI - Substrate dependence of energy metabolism in isolated guinea-pig cardiac muscle: a microcalorimetric study. AB - 1. The effects of glucose, pyruvate and lactate on basal metabolism and on contraction-related energy expenditure of thin trabeculae isolated from guinea pig heart were studied using a microcalorimetric technique. 2. Resting heat rates of cardiac ventricular muscle measured in the presence of substrate-free solution (56 +/- 20 mW (g dry weight)-1), 10 mM-lactate (54 +/- 12 mW (g dry weight)-1) and 10 mM-glucose (63 +/- 24 mW (g dry weight)-1) did not differ significantly. Increasing the external glucose concentration (up to 100 mM) and/or adding insulin (up to 80 units l-1) had virtually no effect on the measured resting heat rate. 3. With 10 mM-pyruvate as substrate resting heat rate was substantially larger (106 +/- 40 mW (g dry weight)-1) than with glucose, lactate or substrate free solution. The concentrations of pyruvate producing a half-maximal increase in resting heat rate as compared to substrate-free solution ranged between 0.4 and 1.2 mM. 4. In order to test whether the development of an anoxic core contributed to the substrate dependence of resting heat production the critical PO2 (i.e. the PO2 that produced a just-noticeable decrease in heat rate) was determined in cylindrical preparations of various diameters. It was found that none of the preparations had an anoxic core at rest in a solution equilibrated with 100% oxygen. 5. From the dependence of the critical PO2 on the diameter of the preparation the diffusion coefficient of oxygen through cardiac muscle was calculated using a modification of Hill's equation (Hill, 1928). The O2 diffusion coefficient was found to be 1.09 X 10(-5) cm2 s-1. 6. Contraction-related heat production was also found to be dependent on the substrate used. In the presence of 10 mM-pyruvate it was about 60% larger than in the presence of 10 mM-glucose, 10 mM-lactate or with substrate-free solution. 7. Isometric force of contraction showed the same substrate dependence as contraction-related heat production and increased with a similar time course during repetitive stimulation. 8. The possible mechanisms underlying the substrate dependence of myocardial energy metabolism are discussed. It is suggested that the increased energy expenditure observed in the presence of pyruvate may be related to a decrease in intracellular phosphate and/or to an increase in intracellular pH. PMID- 2600857 TI - Modulation of K+ currents in human lymphocytes by pH. AB - 1. Using whole-cell patch-clamp techniques, we found that the voltage-dependent K+ conductance in human peripheral blood T lymphocytes is enhanced threefold at alkaline intracellular pH (pHi) compared to acid pHi. This pH dependence can be described by a model having two strongly co-operative proton binding sites with pka 7.15. A similar pHi sensitivity exists for K+ conductance in mitogen activated cells. 2. The reversal potential, threshold voltage for activation of the K+ conductance, and voltage dependence of steady-state inactivation are not affected by pHi. Activation and inactivation kinetics are also unchanged. 3. Single-channel measurements made in whole-cell patch-clamp mode indicate that the effect of intracellular pH on the amplitudes of single-channel events parallels, but does not wholly account for, the effect of pHi on the macroscopic currents. 4. Lowering extracellular pH (pHo) shifts the threshold for activation of the K+ current to a more depolarized voltage, consistent with a surface charge screening effect. Apparent changes in peak current and activation kinetics at acid pHo can be accounted for by this voltage shift. An additional slowing of inactivation kinetics at low pHo does occur. 5. The relevance of the pH sensitivity of the voltage-gated K+ conductance to lymphocyte mitogenesis and volume regulation is discussed. PMID- 2600858 TI - Influence of duodenal digesta composition on abomasal outflow, motility and small intestinal transit time in sheep. AB - 1. A study was made of the influence of duodenal infusion of some of the components of the digesta on gastrointestinal motility, abomasal outflow and small intestinal transit time in seven sheep fed 1500 g grass pellets/day. Gastrointestinal motility was recorded by electromyography. Abomasal outflow was estimated according to the rate of dilution of CrEDTA injected and sampled via an abomasal catheter. Small intestinal transit time was measured by the passage of Phenol Red from the duodenum to the terminal ileum. 2. Abomasal outflow was inhibited during 3 h infusions (5 ml/min) of 100 mM-acetic, propionic, butyric and lactic acids, of 50 mM-HCl, of 0.56 M-glucose, and of 2 and 4% protein hydrolysate. Abomasal motility was inhibited by these infusions and by infusion of 234 mM-oleic acid (0.75 ml/min), of a fat emulsion (Intralipid 20% 0.3 ml/min) and of 50 mM-L-tryptophan (7.5 ml/min). 3. Abomasal motility and, where tested, abomasal outflow, were not affected by duodenal infusion of 150 mM-NaHCO3 (5-10 ml/min), 0.28 M-NaC1 (5-7.5 ml/min), distilled water (5-7.5 ml/min), 25 mM-L tyrosine (5 ml/min), and of 50 mM-acetic, propionic, butyric and lactic acids (5 ml/min). 4. At concentrations or rates of infusion above the threshold dose needed to inhibit abomasal motility, small intestinal motility was altered and the frequency and amplitude of the reticulo-ruminal contractions were inhibited. 5. The transit time through the small intestine was increased during infusion of 100 mM-acetic, propionic, butyric and lactic acids and decreased during infusion of 0.56 M-glucose and Intralipid. 6. Inhibition of abomasal motility and outflow in sheep receiving 1500 g/day grass pellets was calculated to require increases in the duodenal concentration of volatile fatty acids of about 150% and K+ of about 38%, and to require an increase in the rate of delivery to the duodenum of H+ of about 90%, nitrogen of about 22% glucose of about 2000% and fat of about 84%. 7. These findings are discussed in relation to the composition of abomasal and duodenal digesta in sheep fed different diets. 8. It seems likely that components of duodenal chyme, such as H+, volatile fatty acids, glucose and fat only affect abomasal outflow in sheep fed high-grain diets (glucose, volatile fatty acids), or diets highly supplemented with fat (fat), for short periods after meal feeding (volatile fatty acids) or under abnormal conditions (H+).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600859 TI - Autonomic blockade and cardiovascular responses to static exercise in partially curarized man. AB - 1. The cardiovascular responses, heart rate and mean arterial pressure, were followed in seventeen human subjects who performed static handgrip contractions for 2 min at the same absolute force (15% of the initial maximal voluntary contraction strength) before and during partial curarization. In control contractions the rate of perceived exertion was 10 exertion units, 16 units in contractions with tubocurarine which could be maintained and 20 units in contractions that could not be maintained. Control contractions increased mean arterial pressure by 6 mmHg from 89 mmHg while heart rate was unchanged from the resting value of 68 beats min-1. With tubocurarine, larger increases in mean arterial pressure of 11 mmHg and for heart rate of 8 beats min-1 were obtained during maintained contractions, and 15 mmHg and 16 beats min-1, respectively, during non-maintained contractions. 2. Atropine increased resting heart rate and blood pressure with tubocurarine to 107 beats min-1 and 98 mmHg, respectively, in seven subjects. The blood pressure response to exercise with tubocurarine was unaffected by atropine, but the heart rate increase was reduced from 15 to 4 beats min-1. 3. Propranolol reduced resting heart rate with tubocurarine to 56 beats min-1 with no effect on blood pressure in seven subjects. The cardiovascular responses to exercise with tubocurarine were unaffected by propranolol. In contrast, phentolamine reduced resting blood pressure with tubocurarine to 80 mmHg without affecting heart rate in seven subjects. Exercise responses with tubocurarine were unaffected by phentolamine. Combinations of atropine and propranolol in fourteen subjects or atropine and phentolamine in five subjects showed similar results during exercise with tubocurarine as with the sole use of the agents used to block autonomic receptors. 4. The results suggest that when partial curarization induces a disproportion between the signal from central command and that from exercising muscles, the larger signal arising from central command determines the magnitude of the cardiovascular responses. The centrally generated heart rate response is in part caused by vagal withdrawal. However, the blood pressure response cannot be attenuated by the sole use of alpha- or beta-receptor adrenergic blockade or combinations of these with atropine. This suggests that there may be greater redundancy in the autonomic control of blood pressure than in the vagal control of heart rate associated with central command during static exercise in man. PMID- 2600860 TI - Desensitization to cytoplasmic Ca2+ and Ca2+ sensitivities of guinea-pig ileum and rabbit pulmonary artery smooth muscle. AB - 1. The free cytoplasmic Ca2+ concentration [( Ca2+]i) was measured in the tonic rabbit pulmonary artery and the phasic ileum smooth muscle. 2. Force development and [Ca2+]i were determined during either cumulative or non-cumulative additions of [Ca2+]o to smooth muscles depolarized with 140 mM-K+ solutions. 3. The level to which [Ca2+]i declined in Ca2+-free, 140 mM-K+ solutions was significantly lower in the ileum (40 +/- 4 nM) than in pulmonary artery (77 +/- 5 nM) smooth muscle. 4. The level of [Ca2+]i reached during non-cumulative superfusion with 10 microM and 1 mM [Ca2+]o was higher in the pulmonary artery than in the ileum. 5. The force level reached for a given [Ca2+]i was also higher in the pulmonary artery than in the ileum. 6. During maintained depolarization there was a marked decrease in the sensitivity of ileum smooth muscle tension to [Ca2+]i. 7. We conclude that significant differences exist in the Ca2+ sensitivity of the regulatory/contractile apparatus among different smooth muscles; the lower sensitivity of depolarized ileum than pulmonary artery to [Ca2+]o is due to both differences in Ca2+ metabolism and in the Ca2+ sensitivity of the regulatory contractile system. We suggest that these two mechanisms also contribute to the decline in force during a phasic K+ contracture, and that desensitization to [Ca2+]i contributes to the decline of the K+ contracture in the ileum. PMID- 2600861 TI - Macroscopic K+ currents in single smooth muscle cells of the rabbit portal vein. AB - 1. Single smooth muscle cells isolated from rabbit portal vein were voltage clamped at room temperature using the whole-cell configuration of the patch-clamp technique. These cells exhibited a mean resting potential of -47.9 mV and a mean input resistance of 376 M omega. 2. Using small tip diameter micropipettes (to avoid dialysis of the cells), depolarizing voltage-clamp pulses from a holding potential of -50 mV elicited two distinct outward currents: a quasi-instantaneous background current and a time-dependent current that did not appear to inactivate (delayed rectifier). Upon return to the holding potential, an outward tail current decaying back to the holding current was observed. 3. The time course of development of the tail current as estimated from envelopes of tail current protocols followed the kinetics of activation of the delayed rectifier elicited during the preceding test pulse. The tail current reversed close to the equilibrium potential for K+ ions indicating that it is mainly carried by potassium ions. 4. Using large tip diameter micropipettes to internally dialyse the cells (EGTA = 0.1 mM; ATP = 5 mM), two additional outward currents having transient kinetics were revealed: a smooth transient outward current (Ito) and spontaneous transient outward currents (STOCs). Ito was found to be mainly selective for K+ ions and exhibited voltage-dependent inactivation with half maximal availability near -40 mV. 5. Removal of calcium from the bathing solution significantly reduced the background current and abolished both Ito and STOCs. The delayed rectifier current appeared to be insensitive to this procedure. The two types of transient outward currents were never recorded when EGTA was elevated to 5 mM inside the micropipette whereas the background and delayed rectifier currents were not affected. These results suggested that Ito and the spontaneous transient outward currents are activated by internal calcium. 6. External application of TEA (0.5-20 mM) blocked all four outward currents. Calcium replacement by barium significantly reduced the background current and Ito, and had small effects on the delayed rectifier current. When potassium was replaced with caesium (130 mM) and TEA (20 mM) inside the pipette, none of the outward currents described was ever observed. In about 60% of the cells dialysed with this solution a small inward Ca2+ current was revealed. 7. External application of caffeine (5 mM) abolished STOCs in cells in which this activity was present under control conditions. In cells lacking this type of activity under control conditions caffeine induced and later abolished this type of current.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600862 TI - Neurogenic slow depolarizations and rapid oscillations in the membrane potential of circular muscle of mouse colon. AB - 1. Intracellular microelectrodes have been used to record the electrical activity of smooth muscle cells of the circular layer from full length strips of mouse colon in vitro. The membrane potential was unstable and showed slow depolarizations (mean amplitude, 10.9 mV; mean frequency, 0.008 Hz; mean duration, 56.4 s). 2. A variable number (mean fifty-six) of rapid oscillations in membrane potential (mean amplitude, 10.2 mV) with a frequency of approximately 2 Hz and a duration of approximately 400 ms were superimposed on each slow depolarization. Occasionally, action potentials arose from the rapid oscillations. The action potentials, but neither the slow depolarizations nor the rapid oscillations, were abolished by 1.0 microM-nifedipine. 3. The majority of the slow depolarizations and the associated rapid oscillations migrated aborally along the colon at a velocity of between 0.5 and 1.5 mm s-1; in the distal colon the slow depolarization was often preceded by a small hyperpolarization. 4. During the rising and plateau phase of the slow depolarization the amplitude of electronic potentials was decreased. Hyperpolarization induced by passing current during the slow depolarization increased the amplitude of the rapid oscillations. 5. Transmural electrical stimulation (single pulses) in the presence of nifedipine evoked (1 mm anal to the stimulating electrodes) an inhibitory junction potential which was sometimes preceded by an excitatory junction potential. The amplitude, of the evoked inhibitory junction potential was decreased during the rising and plateau phase of the slow depolarization. 6. The slow depolarization and the rapid oscillations were abolished by hexamethonium (500 microM), morphine (1-10 microM) and tetrodotoxin (3.1 microM). Atropine (3.5 microM) abolished the rapid oscillations and reduced the amplitude of the slow depolarization. 7. Atropine (3.5 microM) and morphine (10 microM) abolished the evoked excitatory junction potential whilst tetrodotoxin (3.1 microM) abolished both the excitatory and the inhibitory junction potential. 8. It is suggested that the migrating depolarization and accompanying oscillations, which are neurogenic in origin, represent the electrical correlate in the circular muscle layer of the migrating colonic motor complex which has been associated with the propulsion of faecal pellets along the colon. PMID- 2600863 TI - Contribution of human short-wave cones to luminance and motion detection. AB - 1. Human short-wave S cone signals are important for colour vision and here we examine whether the S cone signals also contribute to motion and luminance. 2. Detection was measured with moving patterns that selectively stimulated S cones violet sine-wave gratings of 1 cycle deg-1 on an intense yellowish field. For rates up to 12 Hz, detection was governed by non-directional mechanisms, possibly of a chromatic nature, as shown by three findings: moving gratings had to be suprathreshold for their direction to be identified; the threshold ratio of counterphase flickering versus moving gratings was low; and direction-selective adaptation was essentially absent. 3. Evidence for less sensitive, directional mechanisms includes the following: at high velocity, the direction of movement of the violet gratings can be identified just slightly above the detection threshold; directional adaptation was strong with a suprathreshold test pattern; velocity was seen veridically for clearly suprathreshold patterns; and a counterphase flickering test, added in spatial-temporal quadrature phase to a similar suprathreshold mask, had identical detection and direction-identification thresholds. 4. Interactions of long-wave L cone and S cone signals in direction selective mechanisms were measured with an orange counterphase grating and a violet counterphase test, both flickering at the same rate and presented in spatial quadrature phase on the yellowish adapting field. Direction identification thresholds, measured as a function of the temporal phase of two gratings, demonstrated both that the S cone signal lags considerably behind the L cone signal (an effect that strongly varies with S cone light adaptation), and more strikingly, the S cone signal summates with a negative sign and thus is effectively inverted in direction-selective mechanisms. 5. Quantitatively similar temporal phase functions were obtained with uniform violet and orange flicker when a luminance discrimination criterion was used: thus the S cone signal summates negatively with the L cone signal for both discrimination of luminance flicker and the direction of motion. 6. The temporal phase functions accurately predicted threshold summation for identifying the direction of motion of a pair of violet and orange gratings moving with the same velocity but with different spatial phase offsets. Once the relative temporal phase lag of the S cones was compensated for, there was linear threshold summation for the violet and orange patterns when presented in effective (physiological) spatial antiphase, and clear cancellation when presented in phase. This and related experiments show a linear summation of S, M and L cone signals for direction detection, with the S cones having a negative sign.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600865 TI - Development of a custom-fit mouthstick appliance. AB - Quadriplegics rely on mouth-controlled devices to perform a variety of tasks and to establish some degree of self-sufficiency. The most functional mouthstick appliances have custom-fitted mouthpieces which are fabricated by dental professionals, and in some cases are cost-prohibitive. An inexpensive lightweight mouthstick which incorporates a new thermoplastic mouthpiece and can be custom fitted by the user is described. PMID- 2600864 TI - Electrical muscle stimulation for pressure variation at the seating interface. AB - A new method is proposed for pressure sore prevention using electrical muscle stimulation (EMS). Potential mechanisms through which EMS may act for this purpose are discussed, including both short-term/dynamic and chronic effects. Measurements of maximum pressure variation in three able-bodied subjects using low levels of stimulation were performed. Pressure distribution changes were also measured. Fatigue effects on pressure redistribution were studied for four able bodied subjects as well as for one C4, complete spinal cord injured individual. The results indicate that EMS produces sizeable pressure reduction under the ischial tuberosity, with redistribution occurring over other parts of the seating surface in able-bodied subjects. Fatigue effects were not observed in the four able-bodied subjects even after prolonged stimulation. Fatigue was observed with the spinal cord injured subject, but only after extensive stimulation. These studies demonstrate the feasibility of using EMS at relatively low intensity to vary seating interface pressure. The results warrant continued investigation of EMS to assist in pressure sore prevention. PMID- 2600866 TI - Computer-aided design in wheelchair seating. AB - This paper describes the integration of computer-aided design (CAD) with the design and fabrication of wheelchair seats. The use of CAD during the design phase permits personal seating for adult and pediatric clientele through a series of standard manufactured seating components. The advent of CAD has permitted the creation of databases of detailed 3-D wheelchair structures that are commercially available, in addition to most standard modular seating components. Direct on screen manipulation of these components on any selected wheelchair structure is through user-friendly software. When using CAD, structural and physical limitations can be foreseen and taken into consideration during the routine initial fitting on an adjustable simulation fitting chair. The end product is a dimensioned drawing of the seating arrangement as it is positioned in the wheelchair structure. The seating components are manufactured from this drawing. The CAD system permits seating specialists to simulate a client's seating arrangement on the wheelchair in order to determine a functional position before the fabrication phase. Essentially, the CAD software is used as a simulation tool for creating functional seating units. It is also a design tool that allows access through a database to dimensional information about commercial seating products and seating products developed through the use of the CAD system. PMID- 2600867 TI - Seat height in handrim wheelchair propulsion. AB - To study the effect of seat height on the cardiorespiratory system and kinematics in handrim wheelchair ambulation, nine non-wheelchair users participated in a wheelchair exercise experiment on a motor-driven treadmill. The subjects conducted five progressive exercise tests. After an initial try-out test, four tests were performed at different standardized seat heights of 100, 120, 140, and 160 degrees elbow extension (subject sitting erect, hands on the rim in top-dead center = 12.00 hrs; full extension = 180 degrees). Each test consisted of four 3 minute exercise blocks at speeds of respectively 0.55, 0.83, 1.11, and 1.39 m.s-1 (2-5 km.hr-1). Analysis of variance revealed significant effects of seat height (P less than 0.05) on gross mechanical efficiency (ME), oxygen cost, push range, and push duration, and on the ranges of motion in the different arm segments and trunk. Mean ME appeared higher at the lower seat heights of 100 and 120 degrees elbow extension. This is reflected in an enhanced oxygen consumption at seat heights of 140 and 160 degrees elbow extension. Simultaneously, the push range showed a 15 to 20 degree decrease with increasing seat height, which is reflected in a decreased push duration. In the push phase, decreases in retroflexion and abduction/adduction of the upper arm were seen. The trunk shifted further forward, and the motion range in the elbow joint shifted to extension with increasing seat height. No shifts in minimum and maximum angular velocities were seen with increasing seat height. The results showed an interrelationship between wheelchair seat height and both cardiorespiratory and kinematic parameters. With respect to the cardiorespiratory system, the optimization of the wheelchair geometry, based on functional characteristics of the user, appears beneficial. PMID- 2600868 TI - The effects of vocoder filter configuration on tactual perception of speech. AB - Perception of synthetic speech continua through the sense of touch and audition was compared utilizing a 32-channel spectrally-oriented electrocutaneous vocoder display and standard auditory psychophysical procedures. Perception of a consonantal and a vocalic continuum was evaluated utilizing three vocoder filter configurations: logarithmic, linear, and average (geometric mean of logarithmic and linear). Results indicated a close correspondence between tactual and auditory discrimination and identification for the vowel (/a/-/e/) and the consonant (/sta/-/sa/) continuum regardless of the filter characteristics. PMID- 2600869 TI - Pharmacodynamics and pharmacokinetics of the oral antispastic agent tizanidine in patients with spinal cord injury. AB - The efficiency and duration of action of a single oral dose (8 mg) of tizanidine in patients with spinal cord injuries were determined by studying its antispastic, cardiovascular and sedative effects along with its pharmacokinetic profile in five tetraplegic and five paraplegic patients. After the administration of tizanidine, there was a reduction in spasticity in both groups within half an hour, with the effects lasting for 3 to 4 hours. There was no rebound increase in blood pressure. There was a greater increase in sedation in the tetraplegics than in the paraplegics. Plasma tizanidine levels rose within half an hour after dosing and peaked at one hour. The levels had fallen to 15 percent by 6 hours. The plasma half-life was 2.7 +/- 0.06 hours. We conclude that oral tizanidine has antispastic effects in patients with spinal cord injuries without affecting the power of non-involved muscle groups. It has minimal effects on blood pressure and it lowers heart rate. Side effects include sedation and dryness of mouth. PMID- 2600870 TI - [Inhibitory mechanism of acupuncture and moxibustion stimulation on the exteroceptive vibration-induced finger flexion reflex in man]. AB - This study indicates that acupuncture and moxibustion stimulation on one side can inhibit Exteroceptive vibration-induced finger flexion reflex (VFR) produced by vibration on the surface of the skin of fingers of both hands. This was thought to be due to that transmission of impulses in the spinal cord producing VFR was inhibited bilaterally, when unilateral acupuncture or moxibustion stimulus was applied. The degree of inhibition with acupuncture and moxibustion stimulation was, in decreasing order, electroacupuncture (insulated needle), electroacupuncture (stainless needle), leaving needle, indirect moxibustion and cold moxibustion in the ipsilateral side, and the order of the leaving needle and the indirect moxibustion was reversed in the contralateral side. By investigating the effects of stimulation of meridian points and their neighboring places, the location of stimulation where VFR was effectively inhibited was found. Furthermore, the role played by the organization metamerism was demonstrated. Also prostaglandin was considered to mediate the effects of acupuncture stimulation on VFR. Concurrent stimulation of the Hegu (LI4) and Baihui (GV 20) did not inhibit VFR. In many of the subjects with no manifestation of VFR, VFR occurred when acupuncture stimulus was applied to the Baihui. PMID- 2600871 TI - Organ donations--facts and fallacies. PMID- 2600872 TI - Preventing falls. PMID- 2600873 TI - Re-examining our responsibilities to older clients. PMID- 2600874 TI - Your CE topic this month (No. 104). Antidepressant drug therapy for geriatric patients. PMID- 2600875 TI - The disruptive visitor: when nursing intervention includes a request to leave the premises. PMID- 2600876 TI - HHS establishes community AIDS treatment research programs. PMID- 2600877 TI - FDA approves the distribution of AZT for children. PMID- 2600878 TI - Redescription of flagellar arrangement in the duck intestinal flagellate, Cochlosoma anatis and description of a new species, Cochlosoma soricis n. sp. from shrews. AB - Cochlosoma anatis Kotlan (Zoomastigophorea, Retortamonadida, Cochlosomidae), isolated from the large intestines of domestic Rouen ducks, and Cochlosoma soricis n. sp., isolated from the small intestines of shrews, were observed by light and scanning electron microscopy. In both organisms, a single flagellum inserted on the dorsal surface at the same level as the insertion of 4 other flagella on the ventral surface. The 4 ventro-lateral flagella emerged from the left side of the anterior attachment disk below the margin and just above the lateral groove which extended the length of the organism. A 6th flagellum emerged from the margin of the attachment disk. The proximal ends of the flagella formed a bundle with the distal ends becoming unraveled like a rope. During motility, the bundle portion extended straight out from the cell and the free ends of the flagella produced a whipping motion. In C. anatis, the dorsal surface was covered with knob-like lumps and small pits and the cells had an axostyle that emerged slightly to the right of the midline in the posterior 1/3 of the body. The axostylar tip was shorter and thicker than the flagella and in most cells it also had an irregular, knobby appearance. The irregular cell surface and axostyle were absent from C. soricis. The margin of the attachment disk curved toward the center and terminated in C. anatis as a straight edge while in C. soricis it continued as a spiral. Indentations in the mucosal brush border similar to those produced by Giardia, but distinctly belonging to Cochlosoma, were interpreted as points of attachment to the host. PMID- 2600879 TI - Antigenic reactivity of a monoclonal antibody against Amoeba proteus actin. AB - The reactivity of a monoclonal antibody against actin of Amoeba proteus with actins from other sources was examined. The monoclonal antibody cross-reacted with actins from vertebrate muscles, human erythrocytes, and Acanthamoeba castellanii, but it did not react with Naegleria gruberi actin. The amoeba actin was resolved into 3 bands with isoelectric points of 5.96, 6.03 and 6.10 in electrofocusing gels and they corresponded to 3 peptide spots reacting with the antibody on 2-dimensional immunoblots. PMID- 2600880 TI - Mechanism of long slender (LS) to short stumpy (SS) transformation in the African trypanosomes. AB - The transformation of the long slender to the short stumpy stages of the African trypanosomes is an essential part of the trypanosome life cycle. Four possible mechanisms which could control this event have been investigated. It has been shown that (a) the dividing long slender to non-dividing short stumpy transition is not a programmed event in the trypanosome life cycle; nor (b) would it appear to be initiated by some form of cell to cell contact inhibition of growth. In addition, evidence is presented which would suggest that (c) the transition is not started by the depletion of a critical growth nutrient from the environment during the growth of the trypanosomes. The last possibility (d) considered is that during trypanosome growth, a growth inhibitor-short stumpy inducer accumulates in the trypanosomes' environment. Evidence is presented which shows that plasma from infected animals can inhibit the incorporation of thymidine by the trypanosomes. These data are consistent with the suggestion of an exogenous growth inhibitor accumulating during the infection. PMID- 2600881 TI - Properties of purified L-ornithine decarboxylase (EC 4.1.1.17) from Tetrahymena thermophila. AB - Ornithine decarboxylase (ornithine carboxy lyase; EC 4.1.1.17) (ODC) from Tetrahymena thermophila was purified 6,300 fold employing fractionated ammonium sulfate precipitation, gel permeation chromatography on Sephadex G-150, ion exchange chromatography on DEAE-Sepharose CL-6B, and preparative isoelectric focussing. The product obtained in 24% yield was a preparation of the specific activity of 10,200 nmol CO2.h-1.mg-1. The purified enzyme was rather stable at 37 degrees C (14% loss of activity within 1 h). The molecular and catalytic properties of this enzyme were investigated. The isoelectric point was 5.7 and the molecular weight (MW) was estimated to be 68,000 under nondenaturing conditions. The pH optimum was between 6.0 and 7.0, the Km for the substrate L ornithine was 0.11 mM, and the Km for the cofactor pyridoxal 5-phosphate was 0.12 microM; the product of ODC catalysis, putrescine, was a poor inhibitor with an estimated Ki of about 10 mM. The enzyme was inhibited competitively by D ornithine with a Ki of 1.6 mM and by alpha-difluoromethylornithine with a Ki of 0.15 mM. The latter one, an enzyme activated irreversible inhibitor of mammalian ODC, inactivated the enzyme from T. thermophila at high concentrations with a half life time of 14 min. Other basic amino acids, e.g. L-lysine, L-arginine, and L-histidine, were neither substrates nor inhibitors of the enzyme, as were the diamines 1,3-diaminopropanol and cadaverine, the polyamines spermidine and spermine and the cosubstrate analogues pyridoxal and pyridoxamine-5 phosphate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600882 TI - Oral assembly in left-handed Tetrahymena thermophila. AB - We have investigated oral development in a non-genetically derived left-handed (LH) form of Tetrahymena thermophila, in which the large-scale asymmetry of arrangement of cortical structures is reversed whereas the local asymmetry of ciliary architecture remains normal. Approximately 1/2 of the oral apparatuses (OAs) of LH cells develop in the form of superficial mirror-images of OAs of RH cells. In most of these OAs, membranelles are assembled from the cells' anterior to posterior. Nonetheless, the posterior ends of these membranelles undergo the basal body displacements that lead to a "sculptured" appearance, so that the membranelles of LH OAs become organized as rotational permutations of membranelles of normal RH OAs. Many of these membranelles re-orient to a normal orientation near the end of oral development. Membranelles and undulating membranes (UMs) may develop independently of each other, and formation of postciliary microtubules of UMs is separate from that of ribbed wall microtubules. In some cases, the entire OA develops and remains as a 180 degrees rotational permutation of the normal, resembling the inverted OAs of mirror-image doublets and LH cells of Glaucoma scintillans described by Suhama. We present a model for these complex developmental outcomes. These developmental patterns resemble those described previously and less completely for "secondary" OAs of cells with mirror-image global patterns, including janus cells. The present study demonstrates that such alterations in oral development are not a direct outcome of genotypic changes. PMID- 2600883 TI - Strain differences in amiloride inhibition of NaCl responses in mice, Mus musculus. AB - The effects of lingual treatment with amiloride, an inhibitor of salt taste responses in several mammalian species, on NaCl responses of the chorda tympani nerve were compared between four inbred strains of mouse (BALB/cCrSlc, DBA/2CrSlc, C57BL/6CrSlc and C3H/HeSlc). In C57BL and C3H mice amiloride significantly suppressed responses of the chorda tympani nerve to NaCl at a concentration 0.1 M or more whereas in BALB and DBA mice the drug did not significantly affect the responses to NaCl at any concentration, suggesting a lack of the amiloride-sensitive receptor component for NaCl in the latter two strains. A two-bottle preference test demonstrated that all strains of mouse usually showed no preference for NaCl at any concentration and avoided NaCl at 0.3 M or more, although some differences were observed in that C57BL and C3H mice showed aversive responses to 0.1 and 0.15 M NaCl, whereas BALB and DBA mice were indifferent to these solutions. The results suggest that there exist prominent differences between mouse strains in the amiloride-sensitive component of their salt receptor systems. However, in mice the taste information derived from the amiloride-sensitive receptor component probably has no remarkable effect on behavioral responses to NaCl except for a possible contribution to decreasing aversion thresholds for NaCl by increasing overall taste information about NaCl. PMID- 2600884 TI - Synaptic specificity in the first instar cockroach: patterns of monosynaptic input from filiform hair afferents to giant interneurons. AB - Direct evidence for monosynaptic connections between filiform hair sensory axons and giant interneurons (GIs) in the first instar cockroach, Periplaneta americana, was obtained using intracellular recording and HRP injection followed by electron microscopy. GIs 1-6 all receive monosynaptic input from at least one filiform afferent axon. GI1, GI2 and GI5 receive input only from the medial (M) axon, while GI3, GI4 and GI6 receive input from both M and lateral (L) axons. The dendrites of GI3 and GI6 which are contralateral to the cell bodies receive input from both axons whereas the smaller ipsilateral dendritic fields have synapses only from the L axon. GI5 has M axon input only onto its contralateral dendrites. In 50% of preparations GI7 receives weak input from the ipsilateral L axon. There is no obvious relationship between the morphology of the giant interneurons and the pattern of input they receive from the filiform afferents. PMID- 2600885 TI - Learning and discrimination of coloured papers in the walking blowfly, Lucilia cuprina. AB - A new training and testing paradigm for walking sheep blowflies, Lucilia cuprina, is described. A fly is trained by presenting it with a droplet of sugar solution on a patch of coloured paper. After having consumed the sugar droplet, the fly starts a systematic search. While searching, it is confronted with an array of colour marks consisting of four colours displayed on the test cardboard (Fig. 1). Colours used for training and test include blue, green, yellow, orange, red, white and black. Before training, naive flies are tested for their spontaneous colour preferences on the test array. Yellow is visited most frequently, green least frequently (Table 2). Spontaneous colour preferences do not simply depend on subjective brightness (Table 1). The flies trained to one of the colours prefer this colour significantly (Figs. 5 and 9-11). This behaviour reflects true learning rather than sensitisation (Figs. 6-7). The blue and yellow marks are learned easily and discriminated well (Figs. 5, 9, 11). White is also discriminated well, although the response frequencies are lower than to blue and yellow (Fig. 11). Green is discriminated from blue but weakly from yellow and orange (Figs. 5, 9, 10). Red is a stimulus as weak as black (Figs. 8, 9). These features of colour discrimination reflect the spectral loci of colours in the colour triangle (Fig. 14). The coloured papers seem to be discriminated mainly by the hue of colours, but brightness may also be used to discriminate colour stimuli (Fig.13). PMID- 2600886 TI - Medullary reticular neurons in the Japanese toad: morphologies and excitatory inputs from the optic tectum. AB - 1. To elucidate the neural mechanisms that mediate visual responses of optic tectum (OT) to medullary and spinal motor systems, we analyzed medullary reticular neurons in paralyzed Japanese toads (Bufo japonicus). We examined their responses to electrical stimulation of OT, and stained some neurons intracellularly. Responses to stimulation of the glossopharyngeal nerve (IX) were also analyzed. 2. Extracellular single unit recording revealed excitatory responses of medullary neurons to OT and IX stimulation. Among 92 units encountered, 79 responded to OT stimuli, 10 to IX stimuli, and 3 to both. Some units responded to successive stimuli of short intervals with relatively stable lags. 3. Intracellular recording and staining experiments revealed morphologies of reticular neurons that received excitatory inputs from OT. Thirteen units were identified after complete reconstruction of somata and dendrites. Neurons in the nucleus reticularis medius received excitatory inputs from bilateral OT. They had wide dendrites in ventral, ventrolateral and lateral funiculi, and single axons descending in the ipsilateral ventral funiculus as far caudally as the cervical spinal cord. Some collaterals of these axons projected directly to the hypoglossal and spinal motor nuclei. Some neurons in other medullary nuclei (nuc. reticularis superior, pretrigeminal nucleus, nuc. reticularis inferior, and nuc. tractus spinalis nervi trigemini) also responded to the OT stimulation. 4. Activities in bilateral OT converge onto medullary reticular neurons, which may directly control medullary and spinal motor systems. PMID- 2600887 TI - Neural response to very low-frequency sound in the avian cochlear nucleus. AB - Recordings were made in the chick cochlear nucleus from neurons that are sensitive to very low frequency sound. The tuning, discharge rate response and phase-locking properties of these units are described in detail. The principal conclusions are: 1. Low frequency (LF) units respond to sound frequencies between 10-800 Hz. Best thresholds average 60 dB SPL, and are occasionally as low as 40 dB SPL. While behavioral thresholds in this frequency range are not available for the domestic chick, these values are in good agreement with the pigeon behavioral audiogram (Kreithen and Quine 1979). 2. About 60% of the unit population displays tuning curves resembling low-pass filter functions with corner frequencies between 50-250 Hz. The remaining units have broad band-pass tuning curves. Best frequencies range from 50-300 Hz. 3. Spontaneous discharge rate was analyzed quantitatively for LF units recorded from nucleus angularis. The distribution of spontaneous rates for LF units is similar to that seen from higher CF units (300 5000 Hz) found in the same nucleus. However, the spontaneous firing of LF units is considerably more regular than that of their higher CF counterparts. 4. Low frequency units with low spontaneous rates (SR's less than 40 spikes/s) show large driven rate increases and usually saturate by discharging once or twice per stimulus cycle. Higher SR units often show no driven rate increases. 5. All LF units show strong phase-locking at all excitatory stimulus frequencies. Vector strengths as high as 0.98 have been observed at moderate sound levels. 6. The preferred phase of discharge (relative to the sound stimulus) increases with stimulus frequency in a nearly linear manner. This is consistent with the LF units being stimulated by a traveling wave. The slope of these phase-frequency relationships provides an estimate of traveling wave delay. These delays average 7.2 ms, longer than those seen for higher CF auditory brainstem units. These observations suggest that the peripheral site of low frequency sensitivity is the very distal region of the basilar papilla, an area whose morphology differs significantly from the rest of the chick basilar papilla. 7. LF units are described whose response to sound is inhibitory at frequencies above 50 Hz. PMID- 2600888 TI - Melatonin accelerates reentrainment of the circadian rhythm of its own production after an 8-h advance of the light-dark cycle. AB - The rhythm in melatonin production in the rat is driven by a circadian rhythm in the pineal N-acetyltransferase (NAT) activity. Rats adapted to an artificial lighting regime of 12 h of light and 12 h of darkness per day were exposed to an 8-h advance of the light-dark regime accomplished by the shortening of one dark period; the effect of melatonin, triazolam and fluoxetine, together with 5 hydroxytryptophan, on the reentrainment of the NAT rhythm was studied. In control rats, the NAT rhythm was abolished during the first 3 cycles following the advance shift. It reappeared during the 4th cycle; however, the phase relationship between the evening rise in activity and the morning decline was still compressed. Melatonin accelerated the NAT rhythm reentrainment. In rats treated chronically with melatonin at the new dark onset, the rhythm had already reappeared during the 3rd cycle, in the middle of the advanced night, and during the 4th cycle, the phase relationship between the evening onset and the morning decline of the NAT activity was the same as before the advance shift. In rats treated chronically with melatonin at the old dark onset or in those treated with melatonin 8 h, 5 h and 2 h after the new dark onset during the 1st, 2nd and 3rd cycle, respectively, following the advance shift, the NAT rhythm reappeared during the 3rd cycle as well but in the last third of the advanced night only. Neither triazolam nor fluoxetine together with 5-hydroxytryptophan administered around the new dark onset facilitated NAT rhythm reentrainment after the 8-h advance of the light-dark cycle. PMID- 2600889 TI - The introduction of a locally-produced drugs formulary in a Royal Naval shore base. PMID- 2600890 TI - Influenza B, Q fever, and the consequences of febrile illness occurring during jungle warfare training: a clinical and serological study. AB - Seventy-one Royal Marines undergoing jungle warfare training were studied clinically and serologically to determine the incidence and consequences of febrile illness. During acclimatization and the early part of the deployment the incidence of illness having an impact on training was low; during the latter part an outbreak of influenza B occurred, with 25 cases diagnosed clinically. Only 12 of these were confirmed serologically, probably because the outbreak was still in progress when the second samples were taken. A further four subclinical cases were uncovered by the serological study. Five cases of heat exhaustion occurred, one Marine suffering two episodes. Four patients required case-vac from the jungle. Three Marines were found to have serological evidence of previous acute Q fever, including the patient who had two episodes of heat exhaustion. This incidence is higher than expected, and warrants further investigation. PMID- 2600891 TI - Ars longa, vita brevis. PMID- 2600892 TI - A day in the life... PMID- 2600893 TI - Royal Naval Medical Staff School--an update. AB - Four significant changes in the training of RN Medical and Nursing personnel have taken place over the past four years, since training was last outlined in the article commemorating the Branch Centenary namely, the resurrection of MA training with a significantly increased throughput than previously; a relocation from Dophin II to purpose-built accommodation in the grounds of Haslar Hospital; the introduction of the QARNNS Medical Assistant, and also that of the Direct Entry QARNNS Registered General Nurse within the Rating Structure. Current training regimes and constraints are highlighted at all levels to familiarize and update the Branch with the changes and to promote a better understanding of the abilities and capabilities of the Royal Naval Medical and Nursing Services. PMID- 2600894 TI - Medico-legal aspects of accidental and non-accidental hanging. PMID- 2600895 TI - The Global Maritime Distress and Safety System. AB - The evolution of modern communications, in particular by satellite, has enabled the development of a Global system for the alerting and coordination of search and rescue organisations in the event of maritime disaster. A brief overview of the components of the system is given after a review of the various official bodies involved in its inception. PMID- 2600896 TI - Fine needle aspiration cytology as part of a three stage diagnostic approach to breast lumps in a District general hospital. AB - Recent studies from specialist breast centres have suggested that fine needle aspiration cytology in conjunction with mammography and clinical examination can provide a prompt and accurate diagnosis of breast lumps. These three methods of diagnosis have been assessed in the context of a district general hospital by analysing 104 consecutive breast lesions with known histology, of which 75 were benign and 29 malignant. The results are presented in terms of the sensitivity and specificity for each method. Fine needle aspiration cytology had a sensitivity for malignancy of 88% (n = 26) and a specificity of 97% (n = 58). Similarly, sensitivity for mammography was 95% (n = 20) and clinical examination 90% (n = 29). Respective specificities were 96% (n = 45) and 83% (n = 75). In none of the 29 patients with breast cancer were all three modalities negative. It is concluded that without specialist breast clinicians and cytologists, a combination of fine needle aspiration cytology, clinical examination and mammography can still provide a degree of preoperative diagnostic accuracy comparable with specialist centres, allowing prompt counselling with all the subsequent benefits. PMID- 2600897 TI - Management of heat stroke. PMID- 2600898 TI - Modulation of intrafollicular oestradiol in explanted hamster follicles does not affect oocyte meiotic status. AB - Mature antral follicles were collected from PMSG-primed hamsters before the LH surge on Day 4 of the oestrous cycle and were incubated individually for 6 or 10 h under 95% O2 and 5% CO2. The relationship between follicle size and follicular fluid volume was established, and both the oestradiol output during incubation and the LH sensitivity of the follicle with respect to induction of meiotic resumption were determined. The data obtained from these initial studies were then applied to experiments in which the oestrogenic status of follicles was altered by pressure injection of solutions into the antral cavity to result in known concentrations in follicular fluid of oestradiol (0-500 microM), the anti oestrogens, tamoxifen (0-200 microM) or enclomiphene citrate (0-500 microM), or an oestradiol-specific antiserum (1:200 dilution of serum). The proportion of immature oocytes (% GV) was determined cytogenetically after follicular incubation. Significant correlations were established between follicle size and both follicular fluid volume (r = 0.90) and follicular oestradiol accumulation (r = 0.96). The minimum concentration of LH tested which induced maximal meiotic resumption (0% GV) was 0.5 microgram/ml. The % GV was not significantly reduced by intrafollicular injection of either of the anti-oestrogens over the concentration ranges tested, or of the oestradiol-specific antiserum, which was injected in an amount adequate to bind all oestradiol accumulated during the incubation. Intrafollicular injection of oestradiol failed to increase the % GV after follicular incubation in the presence of 0.5 microgram LH/ml. From these results we conclude that it is unlikely that oestradiol plays a primary role in the maintenance of meiotic arrest in follicle-enclosed hamster oocytes in vitro. PMID- 2600899 TI - Bovine trophoblast protein-1 complex alters endometrial protein and prostaglandin secretion and induces an intracellular inhibitor of prostaglandin synthesis in vitro. AB - Evidence exists that conceptuses alter endometrial protein secretion and modulate prostaglandin (PG) synthesis and secretion in cattle. The present study was designed to test the effect of bovine conceptus secretory proteins (bCSP) in general and the bovine trophoblast protein-1 complex (bTP-1) in particular on endometrial function. Endometrial explants from cyclic cows (N = 4) at Day 17 after oestrus were incubated for 24h with 0, 4.8, 24 or 120 micrograms BSA/ml, 1 microgram bTP-1/ml or 12.7 micrograms bCSP/ml. Both bCSP and bTP-1 decreased (P less than 0.005) release of radiolabelled macromolecules into medium and incorporation of radio-labelled precursors into tissue compared to BSA-treated tissues but not tissues treated with medium alone. Secretion of a protein of Mr = 14,900 was enhanced by bCSP treatment as compared to treatment with bTP-1 (P less than 0.025). Both bCSP and bTP-1 decreased PGF secretion of explants (P less than 0.01) compared to BSA. Overall, PGE-2 secretion by bCSP- and bTP-1-treated tissues did not differ from that of BSA cultures, but PGE-2 secretion was greater (P less than 0.025) for bTP-1 than bCSP-treated endometrium. Cotyledonary microsomes from parturient cattle were utilized as a PG-generating system for the detection of inhibitors of PG synthesis. PGF synthesis by the generating system was decreased (P less than 0.05) by 9% by cytosol from BSA-treated explants, whereas cytosol from bCSP- and bTP-1-treated explants decreased (P less than 0.01) PGF synthesis by 42% and 35%, respectively. In summary, both bCSP and bTP-1 inhibit PGF secretion, induce synthesis of an intracellular inhibitor of PGF synthesis, and decrease protein synthesis and secretion. The bTP-1 complex therefore alters PG dynamics by explants in a manner that would function to prevent luteolysis and support the establishment of pregnancy. PMID- 2600900 TI - Spermatogenesis in heterozygotes for Robertsonian chromosomal rearrangements from natural populations of the common shrew, Sorex araneus. AB - Twenty-two adult male common shrews were collected from 5 sites in the vicinity of Oxford (UK) close to the zone of hybridization between two karyotypic races. The shrews were subdivided into 3 karyotypic categories: homozygotes, simple Robertsonian heterozygotes (which form one or more trivalents at prophase I of meiosis) and complex Robertsonian heterozygotes (which form a quadrivalent). The ratio of primary spermatocytes to round spermatids was determined from transverse sections of seminiferous tubules, to provide an indication of germ cell death. In no individual was there severe germ cells loss. Homozygotes had the highest mean spermatocyte: spermatid ratio and complex heterozygotes the lowest, but there was substantial individual variation and the differences were not significant. Complex heterozygotes also had a higher proportion of defective seminiferous tubules and lower testis weights than did other categories and it is reasonable to propose that, as a population, complex heterozygotes had reduced fitness relative to other categories on the basis of spermatogenic performance. However, there is no evidence from studies of spermatogenesis that simple Robertsonian heterozygotes are less fit than homozygotes. PMID- 2600901 TI - Regulation of steroidogenesis and cholesterol synthesis by prostaglandin F-2 alpha and lipoproteins in bovine luteal cells. AB - Bovine luteal cells can utilize low density lipoprotein (LDL) or high density lipoprotein (HDL) as a source of cholesterol for steroidogenesis, and administration of PGF-2 alpha in vitro suppresses lipoprotein utilization. The objective of this study was to examine the mechanism by which PGF-2 alpha exerts this effect. Cultured bovine luteal cells received 0.25 microCi[14C]acetate/ml, to assess rates of de-novo sterol and steroid synthesis, with or without lipoproteins. Both LDL and HDL enhanced progesterone production (P less than 0.01), but caused a significant reduction in the amount of radioactivity in the cholesterol fraction. PGF-2 alpha treatment inhibited the increase in lipoprotein induced progesterone synthesis (P less than 0.01), but did not prevent the reduction in de-novo cholesterol synthesis brought about by LDL or HDL. PGF-2 alpha alone reduced cholesterol synthesis (P less than 0.01), but it was not as effective as either LDL or HDL. Both lipoproteins and PGF-2 alpha also decreased the amount of radioactivity in the progesterone fraction (P less than 0.01), and the effect of PGF-2 alpha was similar to that of the lipoproteins. It is concluded that lipoproteins can enhance progesterone production and also suppress de-novo cholesterol synthesis in bovine luteal cells, but only the former effect of lipoproteins is inhibited by PGF-2 alpha. Therefore, it is suggested that PGF 2 alpha allows entry of lipoprotein cholesterol into the cell, but prevents utilization for steroidogenesis. In addition, PGF-2 alpha alone can suppress cholesterol synthesis, as well as decrease conversion of cholesterol to progesterone. PMID- 2600902 TI - Luteinizing hormone response to an oestradiol challenge in 5 intersex pigs possessing ovotestes. AB - After challenge with oestradiol benzoate, the mean maximum LH concentration in 5 XX intersex pigs possessing ovarian and testicular tissue, or only testicular tissue, was 2.10 (+/- 0.41) ng/ml compared with 8.9 ng/ml in mature domestic gilts. These results indicate that exposure of the pig brain to testosterone before Day 30 of gestation is important, or that early testicular secretions other than testosterone are involved in the determination of brain gender. The observation that some intersex pigs show normal oestrous cycles implies that the response to these prenatal factors is primarily quantitative rather than qualitative. PMID- 2600903 TI - Divalent cations, capacitation and the acrosome reaction in human spermatozoa. AB - The extracellular Ca2+ requirements for support of capacitation and the spontaneous acrosome reaction (AR) in human spermatozoa have been evaluated. Motile suspensions were prepared using a swim-up method, incubated for up to 24 h in media of various Ca2+ concentrations, fixed and assessed for occurrence of the AR using transmission electron microscopy. Results indicated that the AR response was significantly lower after incubation in Ca2+-deficient medium (generally less than 10% reacting cells) than in 1.80 mm-Ca2+-containing medium (approximately 15%). In the latter the majority of cells were fully reacted, while in Ca2+ deficient conditions the majority were at intermediate stages of the AR. Subsequent experiments indicated that a maximum AR response required the continuous presence of millimolar Ca2+; preincubation in the presence of micromolar Ca2+ did not prepare the spermatozoa to undergo rapid AR upon increase of Ca2+ to millimolar concentrations, suggesting that capacitation requires relatively high concentrations of extracellular Ca2+. Incubation in elevated Ca2+ (3.60 mM) promoted an even greater response (mean of 24-35% reacting cells compared with 12% for 1.80 mM-Ca2+). The ability of the divalent cations Ba2+, Mg2+ and Sr2+ (each at 1.80 mM) to substitute for 1.80 mM-Ca2+ in promoting the AR was also assessed. Of these, only Sr2+ provided a response greater than that observed in unsupplemented Ca2+-deficient medium. In Sr2+ the proportion of responding cells after 24 h (approximately 13%) was similar to that obtained in Ca2+ (approximately 15%), although a majority of those in Sr2+ were at intermediate stages. In 3.60 mM-Sr2+ the response was significantly higher than that observed in both 1.80 mM-Ca2+ and 1.80 mM-Sr2+, but significantly lower than that in 3.60mM-Ca2+. Under all conditions motility was maintained at greater than 90% for 24 h. The introduction of the Ca2+ ionophore ionomycin, in the presence of 1.80 mM-Ca2+, induced the AR in a concentration-dependent but preincubation time-independent manner, with the maximum response of approximately 60% being obtained with 30 microM-ionomycin. Finally, incubation in the presence of 1.80 mM Ca2+ and verapamil, generally considered to be a calcium channel antagonist, resulted in a concentration- and incubation time-dependent increase in the AR, the maximum response in all groups being observed only after 24 h incubation. Recent evidence from other species suggests that this may represent an agonistic interaction with calcium channels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2600904 TI - High survival rate of unfertilized mouse oocytes after vitrification. AB - Unfertilized mouse oocytes were cooled rapidly by directly plunging them into liquid nitrogen, immediately after exposure to a highly concentrated solution (modified VS1: 2.53 M-dimethyl sulphoxide, 2.36 M-acetamide, 1.19 M-propylene glycol, 5.4% (w/v) polyethylene glycol (Mr 8000) in PB1), and later warmed in a 37 degree C waterbath. After warming, 305 out of 348 oocytes (87.6%) were morphologically normal. After fertilization in vitro of cryopreserved oocytes, the proportions of pronuclear oocytes and 2-cell embryos 5 and 24 h after insemination were 81.6% (124/152) and 78.4% (120/153), respectively. All 2-cell embryos obtained from cryopreserved oocytes were transferred to the oviducts of pseudopregnant recipients and 45.8% (55/120) developed to normal young. PMID- 2600905 TI - Passive immunization of pregnant mice against early pregnancy factor causes loss of embryonic viability. AB - Early pregnancy factor (EPF) is a monitor of the incidence of fertilization and the progress of the early embryo. To determine whether, as well as being a marker of embryonic viability, EPF is also necessary for embryonic survival, passive immunization studies with monoclonal and polyclonal antibodies to EPF were carried out on pregnant mice. In the preparation of monoclonal antibodies, it was noted that most anti-EPF producing hybridomas failed to grow in vitro, while those that did grow produced only low yields of specific IgM antibodies. Two stable hybridoma cell lines were established both producing low affinity anti-EPF IgM; polyclonal anti-EPF IgG was prepared in rabbits. Mice were passively immunized with 500 micrograms monoclonal anti-EPF IgM at 32 and 56 h post coitum (total dose 1 mg) or with 500 micrograms polyclonal anti-EPF IgG at 8, 16, 32 and 40 h post coitum (total dose 2 mg). At 10 days, only 6/18 and 3/6 mice receiving monoclonal antibodies and 2/7 and 1/6 mice receiving polyclonal antibodies had maintained their pregnancies. In contrast, all mice receiving control IgM (N = 14) or control IgG (N = 4) and 22/23 receiving saline were still pregnant at Day 10. PMID- 2600906 TI - Increase in ovarian kallikrein activity during ovulation in the gonadotrophin primed immature rat. AB - The ovulatory process was initiated in 25-day-old rats by injecting them with hCG (10 i.u., s.c.) 2 days after the animals had been primed with PMSG (10 i.u., s.c.). At 2-h intervals after hCG, the ovaries were extracted and assayed for glandular kallikrein activity by using a chromogenic substrate (H-D-Val-Leu-Arg-p nitroanilide) which exhibits optical density (at 405 nm) upon hydrolysis. In 0-h control ovaries the activity was 12.5 x 10(-3) kallikrein units (KU)/mg protein and it increased to a peak of 56.6 x 10(-3) KU/mg at 12 h after hCG, when the follicles first began to rupture. The kallikrein activity was distinguishable from ovarian plasminogen activator activity on the basis of pH optima and response to trypsin inhibitor (SBTI). The activity was inhibited by a s.c. dose of indomethacin of 0.3 mg/rat, or higher, and this dosage inhibited ovulation. The results suggest that kallikrein activity contributes to the degradation of Graafian follicles during ovulation in mammals. PMID- 2600907 TI - Characterization of glycoconjugates in the bovine endometrium and chorion by lectin histochemistry. AB - Lectin binding patterns were examined on normal bovine endometrium and bovine placentomes during four stages of pregnancy using 13 biotinylated lectins. Lectin binding intensity increased in early pregnancy for many lectins, whereas binding to fucosyl residues decreased. Persistence of strong lectin binding later in pregnancy usually was limited to the arcade and intercotyledonary trophoblastic cells. Binding of some lectins to cell surfaces was prominent, particularly in early pregnancy. A few lectins were excellent markers for binucleate trophoblastic cells. These distinctive surface and binucleate cell binding patterns on placentomes and endometrial epithelium are useful markers of trophoblastic cell-endometrial epithelial cell surface interactions and of binucleate cell differentiation. PMID- 2600908 TI - Differences in fertility and suckling patterns between primiparous and multiparous rhesus mothers (Macaca mulatta). AB - Primiparous females gave birth around the same time as multiparous nonlactating females, and earlier than did multiparous lactating females. No differences in birth sex ratio were found between primiparous and multiparous females. During the breeding season following birth, primiparous mothers returned to oestrus later than did multiparous mothers, and while few primiparous mothers conceived successfully during that season, most multiparous mothers did. Primiparous females suckled their infants more frequently than did multiparous females at all ages; infants of primiparous females also made more nipple contacts per bout, and had shorter sucking bouts. When mothers came into oestrus, suckling frequency drastically increased for primiparous females, but not for multiparous females, magnifying the differences between the two groups. After the first oestrus, suckling frequency declined for all mothers, but multiparous mothers had consistently lower suckling frequencies than did primiparous mothers. The high suckling frequency, and numerous nipple contacts per bout, found among primiparous mothers are likely to be related to the low reproductive chances that these females faced during the breeding season. Multiparous mothers seemed to compensate for their low suckling frequency by lengthening the suckling bouts, and this suckling pattern did not hinder their reproduction. It is argued that primiparous mothers might have to suckle their infants more frequently because they can only produce milk at slow rates, being in this way forced into a reproductively inhibiting suckling pattern. However, the delay in subsequent reproduction could be ultimately advantageous for primiparous mothers if it enhanced infant survival, and allowed the mothers to regain physical condition before reproducing again. PMID- 2600909 TI - Spontaneous electromyographic activity throughout the cycle in the sow and its change by intrauterine oestrogen infusion during oestrus. AB - Two experiments were carried out to monitor influences on the uterine electromyographic activity (EMG) in cyclic gilts with chronic uterine EMG electrodes. In Exp. 1 the EMG was recorded continuously from Day -1 for 24 days and was evaluated for frequency, duration and amplitude. Progesterone and oestradiol in peripheral plasma were measured daily. As high amounts of oestrogens are characteristic for boar semen, in Exp. 2 the influence of seminal oestrogens on uterine contractions at Day 0 (first day of standing reflex) was investigated in gilts with chronic intrauterine catheters. They were infused with 10 ml saline (N = 4) or saline with physiological amounts of oestrogens (5 micrograms oestradiol + 2 micrograms oestrone + 4.5 micrograms oestrone sulphate; N = 4). Sham-treated gilts (infusion catheters, no infusion; N = 5) served as controls. The EMG was recorded for 2 h before and 9 h after infusion. In Exp. 1 the maximal amplitude (2040 +/- 98 microV) and duration (32 +/- 1.7 sec) but the lowest frequency (15.8 +/- 2.1 contractions/h) were found on Day 0. With decreasing oestrogen and increasing progesterone concentrations the frequency increased continuously until Day 5 (63.5 +/- 1.0 contractions/h) while the amplitude (183 +/- 13 microV) and duration (3.3 +/- 0.7 sec) decreased. During Days 6-13 the EMG activity was not detectable. The reverse pattern was found from the onset of luteolysis until the following Day 0. On Day 0 a significant correlation between oestradiol and the duration (r = 0.81; P less than 0.01; n = 10) but not the frequency was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2600910 TI - Genetic variation in testicular development in mice of the C57BL/10ScSn, C57BL/6By and BALB/cBy strains and the CXB recombinant-inbred lines. AB - When compared with C57BL/6By mice, BALB/cBy mice had testes that were 41% heavier at 60 days of age and seminiferous tubules that were 41% greater in cross sectional area at 120 days. Absolute testicular weight did not increase between 60 and 120 days of age in either C57BL/6By or C57BL/10ScSn mice but did in BALB mice, paralleling changes in the size of the seminiferous tubules. Significant testicular growth took place over this age period in mice of all seven of the CXB recombinant-inbred (RI) strains of mice derived from a cross of the BALB/cBy and C57BL/6By strains. The wide range of phenotypes shown by adult recombinant mice, which ranged from those with significantly heavier testes than BALB to those with testes the same size (at 60 days) as those of C57BL/10ScSn mice, implied the existence of several separable factors affecting testicular size in adults. At 30 days of age the RI lines fell into two groups; one with small testes like C57BL/6By and the other with larger testes like BALB/cBy mice. The segregation pattern for prepubertal testicular weight was identical to that for the H-2 histocompatibility locus. PMID- 2600911 TI - Relative roles of oestradiol and of the uterus in the maintenance of the corpus luteum in the pseudopregnant brown hare (Lepus europaeus). AB - Brown hares were made pseudopregnant by sterile matings or PMSG-hCG treatment (day of mating or hCG injection = Day 0 of pseudopregnancy). Progesterone secretion by the CL began 3-4 days after the ovulatory stimuli, reached maximum on Days 8 to 11 and decreased thereafter to reach low levels from Day 9 to 18, depending on the female. Cauterization of all large ovarian follicles on Day 7 resulted in an immediate luteolysis in young females, but had no effect in older ones. Oestradiol capsules implanted from Day 7 to Day 46 were able to maintain progesterone secretion until at least Day 30, in intact females as well as in females with all large follicles cauterized. Hysterectomy on Day 7 or 8 was followed by an immediate drop in progesterone concentrations; oestradiol capsules implanted at the time of hysterectomy prevented the drop in progesterone values, which remained elevated until Day 38. The induction of ovulation in females hysterectomized 2 months before resulted in CL of slightly shortened life-span. The injection of PGF-2 alpha on Day 7 of pseudopregnancy was followed by an immediate luteolysis. These results suggest that oestradiol secreted by the large ovarian follicles is the main luteotrophic factor in the brown hare. In old hares, the large amount of interstitial tissue could secrete oestrogens, and thus maintain pseudopregnancy. On Day 7 of pseudopregnancy, the uterus secretes a luteotrophic substance acting either directly on the ovary, or via the pituitary, to maintain oestradiol secretion by the follicles. In long-term hysterectomized females, the CL would be able to develop independently of any trophic substance, but for a reduced duration. PMID- 2600912 TI - Preliminary study of water and some element contents in boar spermatozoa, before, during and after freezing. AB - Boar semen was analysed by electron microscopy coupled to image analysis and X ray energy dispersive spectroscopy, during the usual process for freezing and thawing in field conditions. Freeze-substitution and freeze-quenching permitted recording of real or potential intracellular ice before, during, and after freezing. Heads and flagella displayed two different osmotic properties before freezing. Heads were dehydrated progressively before and during freezing, while flagella were hydrated before freezing and were only dehydrated during freezing. All parts of the thawed cells were rehydrated. Ice crystal damage was mostly present in frozen mitochondria and axonemes and the acrosomes were strongly affected by thawing. The total amounts of Na, Cl, Ca, K, Mg, and Zn per cell were only elevated in frozen and thawed midpieces while the heads were permeable both to water and elements at that time. PMID- 2600913 TI - Impact of asynchronous ovulations on the expression of sex-dependent growth rate in bovine preimplantation embryos. AB - In cattle, male embryos have a faster growth rate than female embryos, and this results in alteration of the normal 1:1 sex ratio in embryos divided into three developmental groups. The fastest developed one-third are predominantly males, the slowest one-third predominantly females, and in the intermediate one-third no alteration of the sex ratio is seen, However, the deviations of the sex ratios are only 15-20% from random. These findings are compatible with the assumption that, in superovulated cows, ovulations follow a normal distribution and that, at the time of sampling at Day 7, male and female embryos differ with regard to development by 1 or 2 h. Because of this it is unlikely that larger changes in the sex ratios can be expected. PMID- 2600914 TI - Evidence that the seasonally breeding Bennett's wallaby (Macropus rufogriseus rufogriseus) does not exhibit short-day photorefractoriness. AB - Adult female Bennett's wallabies (N = 6) were maintained in artificial winter solstitial daylengths commencing 3 weeks before the winter solstice for 16 or 42 weeks. Such treatment effectively prevented the normal establishment of seasonal reproductive quiescence with animals continuing to exhibit reproductive cycles beyond the time of the normal termination of the breeding season. Animals maintained in natural photoperiods or simulated natural changes in daylength after the winter solstice all entered reproductive quiescence by early February. In the Bennett's wallaby, therefore, the breeding season does not terminate as a result of refractoriness to short daylengths. Our results indicate that the relatively small increases in photoperiod shortly after the winter solstice provide the environmental signal responsible for initiating the onset of seasonal reproductive quiescence which normally occurs 5-8 weeks after the solstice. These results contrast with the effect of fixed artificial summer solstitial daylengths on the onset of the breeding season in which breeding begins spontaneously at the normal time of year as a result of long-day photorefractoriness. PMID- 2600915 TI - Effect of a unilateral or bilateral twin embryo distribution on twinning and embryo survival rate in the cow. AB - Uni- and bilateral twin embryo distributions were effected by the transfer of one embryo on Day 7 to the ipsi- or contralateral uterine horn of previously inseminated heifers (123, Exp. 1) or cows (95, Exp. 2). The embryo transfers were surgical in Exp. 1 and non-surgical in Exp. 2. Transferred and native embryos were distinguished by breed. Embryo survival rate was measured in a proportion (N = 40) of the heifers at Day 53 of gestation and in the remainder of the heifers and all of the cows at term. In the heifers (Exp. 1) overall pregnancy rates of 76% and 75% were recorded after uni- and bilateral twin embryo distributions respectively. Twinning rates of 55% and 60% at Day 53 of gestation and 60% and 60% at term were recorded for uni- and bilateral distributions respectively. In the cows (Exp. 2) calving rates of 61% and 63% and twinning rates of 33% and 38% were recorded following uni- and bilateral twin embryo distributions respectively. When the data from both experiments were combined, overall embryo survival rates were similar for both twin embryo distributions although the ipsilateral transfer of an embryo reduced the survival rate of the native embryo. It is concluded that the confinement of two embryos in one uterine horn on or after Day 7 does not depress pregnancy, twinning or overall survival rate to term. PMID- 2600916 TI - Plasma progesterone concentrations in the female Natal clinging bat (Miniopterus schreibersii natalensis). AB - Plasma progesterone concentrations measured by radioimmunoassay in the Natal clinging bat remained below 2.01 ng/ml during lactational anoestrus but increased significantly during the period of delayed implantation. Values peaked at implantation but were followed by a significant decrease thereafter. Concentrations remained low (less than 6.0 ng/ml) during the initial period of fetal development (153-180 days post coitum) and attained peak values (85.6-181.3 ng/ml) 216-222 days after fertilization. The marked post-implantation increase in progesterone concentrations coincided with a significant increase in placental weight. PMID- 2600917 TI - Effects of oestrone sulphate, oestradiol and progesterone on protein sulphation in the guinea-pig uterus. AB - Ovariectomized guinea-pigs were treated with oestradiol-17 beta (ES), oestrone sulphate (E1S) and progesterone (P) and the in-vitro incorporation of 35SO4 was studied in uterine fragments. The net uptake of 35O4 into tissue was only increased by oestradiol-17 beta plus progesterone. The incorporation of 35SO4 in the tissue-associated proteins was increased after treatment with E2 and E1S compared with untreated controls (3.1- and 2.5-fold, respectively). For secreted proteins, all hormone treatments induced an increase in protein sulphation, the highest increase occurring when progesterone was administered after oestrogens. Tyrosine 35SO4 was identified in protein extracts from tissues and media and values were greater after hormone treatments. The biggest increase in tyrosine 35SO4 was observed in secreted proteins in the E1S + P treatment group. The patterns of 35S-sulphate-labelled proteins were examined by SDS-polyacrylamide gel electrophoresis. In tissue extracts, the most striking differences related to the hormone treatments were observed in the Mr 94,000-190,000 region. A sulphated protein band of Mr 102,000 was specifically found in the E2 + P group and a band of Mr 125,000 only in the E1S + P group. The Mr 125,000 band was also found in tissue proteins from the E1S + P-treated animals after the incorporation of 35SO4 in vivo. This protein band may be a marker of the action of oestrone sulphate plus progesterone. For secreted proteins, those with a molecular weight greater than 100,000 were more abundant in the oestrogen plus progesterone-treated groups than in the oestrogen-treated groups. The content of tyrosine sulphate in each protein band ranged from 8 to 25% of the total radioactivity. No protein sulphated exclusively on the tyrosine residues was found. These studies provide the first description of the effects of steroid hormones on sulphated proteins in the guinea-pig uterus and suggest that oestrone sulphate is a potent biologically active hormone in the uterus. PMID- 2600918 TI - Social cues can play a role in timing onset of the breeding season of the ewe. AB - Female Suffolk sheep were pinealectomized around the vernal equinox to eliminate the major environmental input to the reproductive system (photoperiod) and then either isolated from, or maintained with, pineal-intact gonad-intact sheep. The ewes were ovariectomized and treated with constant-release oestradiol implants and reproductive state was monitored by measuring serum LH concentrations. Pinealectomized ewes that were isolated from the normal flock showed a 2 1/2 month delay in onset of the seasonal rise in LH values compared with that of pineal-intact controls (18 November vs 5 September). On the other hand, pinealectomized ewes that were maintained with the flock showed an onset of the seasonal rise in LH that was not delayed. These results suggest a timekeeping role for social cues for timing onset of the breeding season in an animal that normally relies on photoperiodic signals for temporal regulation of the seasonal reproductive cycle. PMID- 2600919 TI - Integrity of the preimplantation pig blastocyst during expansion and loss of polar trophectoderm (Rauber cells) and the morphology of the embryoblast as an indicator for developmental stage. AB - The embryonic ectoderm of the pig differentiated and became part of the outer barrier of the blastocyst (earlier formed by the trophectoderm alone) before shedding of the overlying polar trophectoderm around Day 10, thus securing the integrity of the rapidly expanding blastocyst. Ferritin, added to the medium of the blastocyst, was taken up rapidly by trophectoderm cells, but did not reach the blastocoele, and consequently no tracer was found within hypoblast cells. Embryonic ectoderm cells did not absorb the macromolecule, before or after loss of the polar trophectoderm. When ferritin was injected into the blastocoele, trophectoderm, hypoblast and embryoblast cells all absorbed the tracer. At Day 11, blastocyst diameter and embryoblast cell number varied widely and were hardly correlated. We suggest that embryoblast development may be a more reliable indicator for the developmental stage of a blastocyst than its diameter, which may merely be an indication of the viability of the trophoblast. PMID- 2600920 TI - Fertilizing ability of spermatozoa from aged C57BL/6NNia mice. AB - Spermatozoa from C57BL/6NNia mice (7- and 25-month-old males that produced offspring and 25-month-old males incapable of producing offspring which either mated or did not mate after being paired for 1 month with proven-fertile females) were tested in in-vitro fertilization studies. The 7-month-old males fertilized the largest number of oocytes (80-86%) in vitro and 79% of them subsequently developed into blastocysts in culture. Aged males which failed to mate fertilized the lowest number of oocytes (11-19%) with 48% developing to blastocysts. This group of mice had the lowest number of spermatozoa in the cauda epididymidis (3.2 +/- 0.4 x 10(5)/mg tissue) with fewer motile spermatozoa (22.3 +/- 5.1%) than younger males. The percentage of spermatozoa retaining their acrosome after 3 h in culture was higher in aged males which had not mated when compared to younger males that had mated. After 4 h in culture, however, the number of spermatozoa that had lost their acrosome was almost identical in the two groups. Superovulated mice which were artificially inseminated with spermatozoa from 25 month-old mice that had not mated did not become pregnant. Testosterone concentrations were lowest in aged mice not mating. These concentrations may explain the poor behavioural response of these males, but whether they account for the inability of spermatozoa to fertilize ova in vitro or in vivo after artificial insemination is not known. PMID- 2600921 TI - Morning pulse of prolactin maintains seasonal quiescence in the tammar, Macropus eugenii. AB - The pulse of prolactin, present in female tammars kept in an inhibitory photoperiod and absent 5 days after a change to a stimulatory photoperiod, was artificially maintained during stimulatory photoperiods (Exps 1A and 1B) or abolished during an inhibitory photoperiod (Exp. 2). In Exp. 1A, thyrotrophin releasing hormone (TRH) was injected i.v. for 8 consecutive mornings and in Exp. 1B ovine prolactin was injected i.v. for 10 consecutive mornings beginning on the day the photoperiod was changed from 15L:9D to 12L:12D. In Exp. 1A, in 5 of 6 control females the prolactin pulse was present until the 3rd morning after the lighting was changed, and absent thereafter. In both experiments the early progesterone peak and the interval to birth in the treated females was significantly delayed compared to the control females; reactivation of the CL did not occur until treatment ceased. In Exp. 2, for 5 consecutive mornings, before the prolactin pulse was expected to occur, bromocriptine was injected i.m. In 2/4 treated animals the prolactin pulse was abolished and these animals showed an early progesterone peak and gave birth 28 and 29 days after treatment began. The remaining 2 animals and the controls (N = 4) did not show reactivation until after they experienced a stimulatory photoperiod. The results indicate that the prolactin pulse is the critical factor in the maintenance of the inhibition of the CL of the tammar during seasonal quiescence. PMID- 2600922 TI - Effect of ovine trophoblast protein-1, oestrogen and progesterone on oxytocin induced phosphatidylinositol turnover in endometrium of sheep. AB - In Exp. 1, endometrium was collected from Day-15 cyclic ewes and effects of oTP 1, oxytocin and oTP-1 + oxytocin, in various temporal relationships, on phosphatidylinositol (PI) turnover were determined. Co-treatment of endometrium with oTP-1 and oxytocin inhibited stimulatory effects of oxytocin, while treatment with oTP-1 before and during oxytocin administration had no effect. Turnover of PI was unaffected by oTP-1 alone. In Exp. 2, ovariectomized ewes were treated with progesterone (50 mg/day) for 10 days and then oestrogen (100 micrograms/day) for 2 days and endometrium was collected. Oxytocin stimulated PI turnover in endometrium, but oTP-1 had no effect alone or in combination with oxytocin. In Exp. 3, ovariectomized ewes were treated with corn oil (1 ml/day), oestrogen (50 micrograms/day), progesterone (50 mg/day) or progesterone + oestrogen for 10 days and endometrium was collected. Oxytocin stimulated PI turnover only in ewes that received progesterone. oTP-1 alone had no effect on PI turnover, while co-treatment of endometrium with oxytocin and oTP-1 stimulated PI turnover in ewes treated with progesterone, but not progesterone and oestrogen. Pretreatment of endometrium with oTP-1 stimulated PI turnover when ewes were treated with progesterone or progesterone + oestrogen. Pretreatment of endometrium with oxytocin and then treatment with oTP-1 inhibited PI turnover compared to treatment with oxytocin alone. In Exp. 4, ovariectomized ewes were treated as in Exp. 2. Catheters were placed into the uterine horns and ewes received oTP-1 into one horn and serum into the other twice daily on Days 10-12 of steroid treatment. Endometrium collected on Day 13 was used to measure PI turnover and received either no treatment or oxytocin. Oxytocin stimulated PI turnover in endometrium of these ewes and in-vivo treatment of the ewes with oTP 1 had no effect on PI turnover. These results indicate that antiluteolytic effects of oTP-1 are not mediated by inhibiting effects of oxytocin on phosphatidylinositol turnover if oxytocin receptors are present and that uterine responsiveness to oxytocin is progesterone dependent. PMID- 2600923 TI - Effects of social stress during early pregnancy on litter size and sex ratio in the golden hamster (Mesocricetus auratus). AB - Primiparous female hamsters were mated to proven breeders and stressed during early pregnancy. Females were housed singly throughout gestation except for Days 4, 5 and 6 when they were paired for 10-min intervals 3 times each day with another female matched for age, weight and day of pregnancy. Within each of the pairs, one female was consistently dominant to the other. Controls were exposed to a novel area instead of a conspecific. At parturition, all pups were counted, sexed and weighed. There were no significant differences between litter sizes or sex ratios (defined as % male) of control and dominant females. Litter sizes produced by control or dominant dams were significantly larger than those of subordinate dams, and litter sex ratios of dominants were significantly higher than those of subordinates. Subordinate dams produced fewer males than did dominant dams, but there was no difference in the number of females produced. Also, subordinate dams produced smaller pups than control dams. Examination of uterine implantation sites and fetal resorptions indicated that fetal loss occurred between Days 5 and 10 of pregnancy. These results suggest that subordinate dams produce smaller litters via selective resorption or spontaneous abortion of males in utero and that those males they do produce are smaller than those produced by dominant or control dams. We suggest that males are more susceptible in utero to effects of maternal stress in this species, and may require more maternal investment to survive to term. PMID- 2600924 TI - Aromatase activity in individual day-11 pig blastocysts. AB - Blastocysts were flushed from both uterine horns of 10 gilts on Day 11 of pregnancy. In these gilts 15.1 +/- 2.3 (mean +/- s.d.) corpora lutea were present and 12.7 +/- 3.1 spherical blastocysts were recovered. In all the gilts variation in blastocyst diameter was observed. Aromatase activity was measurable in 118 of 121 examined blastocysts and varied from 0.005 to 19.330 pmol [1 beta 3H]androstenedione converted into 3H2O in 20 min (mean 1.31). This variation in aromatase activity reflected a difference between and within gilts. Of the total variation between all blastocysts, 67% was due to differences between gilts. A positive exponential relationship existed between blastocyst diameter and aromatase activity, but this relationship was different between gilts (P less than 0.0001). The observed variation in aromatase activity may be caused by differences in germ layer differentiation of the blastocysts. PMID- 2600925 TI - Resumption of oestrous behaviour and cyclic ovarian activity in suckling and non suckling ewes. AB - In Prealpes de Sud ewes after an autumn lambing, the mean post-partum interval to first LH surge was 10 +/- 1 days and 17 +/- 1 days for non-suckling and suckling ewes, respectively. Post-partum interval to first luteal phase, estimated from plasma progesterone concentrations, was similar in non-suckling and suckling ewes (27 +/- 1 days and 28 +/- 5 days, respectively). Interval to first oestrus was shorter in non-suckling (22 +/- 2 days) than in suckling ewes (35 +/- 2 days) but these first oestrous periods were followed by short luteal phases in 60% (12/20) of non-suckling ewes and in only 7% (2/29) of suckling ewes. Finally, suckling slightly postponed the resumption of the first oestrus followed by a normal oestrous cycle (37 +/- 1 days versus 31 +/- 2 days) because progesterone, essential for oestrus expression, was secreted mainly during normal luteal phases in 70% (21/30) of suckling ewes and during short cycles in 95% (21/22) of non suckling ewes. Therefore, the primary consequence of suckling is to regulate the conditions of resumption of cyclic ovarian activity after parturition. PMID- 2600926 TI - Effects of naloxone on the oestradiol-induced LH surge and cortisol release in transported cows. AB - Four control cows released a normal LH surge in response to 1 mg oestradiol benzoate i.m. Compared to controls, 30 min transport of 5 cows 16-18 h after oestradiol significantly delayed the onset (P less than 0.05), suppressed the amplitude (P less than 0.01) and reduced the total LH release (P less than 0.001) in 4 cows and totally blocked the surge in the 5th cow. Just before the onset of transport, 5 cows were given 250 mg naloxone i.v. In 3 cows, the LH surge was delayed and reduced in amplitude and duration and was totally blocked in the other two, i.e. naloxone did not avert the detrimental effects of transport. Transport stimulated cortisol release in cows. Cows given naloxone + transport released significantly more (P less than 0.001) cortisol than did those subjected to transport alone. In conclusion, naloxone appeared to have further stimulated the hypothalamopituitary-adrenal axis of cows under stress. PMID- 2600927 TI - Solvent effects on cytoskeletal organization and in-vivo survival after freezing of rabbit oocytes. AB - NBD-phallacidin revealed a polymerized actin distribution in the cortical region of the rabbit egg and along junctional feet. Staining with anti-alpha-tubulin antibody showed that the microtubule distribution was restricted to the barrel shaped spindle. After cryoprotective treatment in the presence of propanediol, cortical polymerized actin was no longer visible within the egg and along junctional feet but filamentous actin was still present after treatment with dimethylsulphoxide. However, exposure to dimethylsulphoxide or propanediol led to the appearance of microtubules in the cytoplasm and to a disassembly of the spindle often associated with anomalies in chromosome position. Cytoplasmic microtubules formed by the action of propanediol were still present after freezing, thawing, and removal of the cryoprotectant, but after recovery of eggs in culture, they disappeared and barrel-shaped spindles were able to reform. When the effect of propanediol addition on in-vivo fertilization and development of frozen oocytes was examined, 39% (79/200) of frozen oocytes were fertilized and 9% (9/105) developed to normal fetuses, compared to 81% (38/47) and 32% (12/38) respectively for unfrozen control oocytes. PMID- 2600929 TI - Society for the Study of Fertility. Winter meeting, 1989. Warwick, 18th-20th December. Abstracts of papers. PMID- 2600928 TI - Pattern of ovarian steroid secretion during ovulation of in vitro perfused rat ovaries varies with method of sampling. AB - Wistar rats were primed at 25 days of age with 20 i.u. PMSG s.c., followed 48 h later with 100 ng LH/ml to induce the ovulatory process in vitro. Assays for progesterone, oestradiol, and testosterone were performed on samples taken at fixed intervals of 0, 1, 2, 4, 8 and 12 h after LH administration. The results show that, while there was some degree of correlation in the concentrations of progesterone between the ovarian extract and perfusate, there were very large differences in the measurable amounts of testosterone and oestrogen in the fluid samples and ovarian homogenates. Therefore, taking samples from the perfusate may not provide a good assessment of the steroidogenic activity in the ovary. PMID- 2600931 TI - Specific neonatally-induced tolerance to rat male accessory glands antigens. Transference of specific suppression by spleen mononuclear cells. AB - The immune response of infant rats was studied following (1) immunization of their mothers with modified rat male accessory glands (MRAG) emulsified in complete Freund's adjuvant (CFA), (5 mg/ml or 25 mg/ml) or with human serum albumin (HSA), (5 mg/ml or 25 mg/ml) and (2) intradermal immunization of the offspring at 21 days of age with 5 mg of MRAG-CFA and 5 mg of HSA-CFA. Antibodies to MRAG or to HSA were observed in the sera obtained 20 days after the birth of the offspring. Delayed hypersensitivity (DTH) against MRAG studied 13 days after immunization was significantly reduced in the male offspring born to mothers immunized with 5 mg of MRAG-CFA compared with that of males born to mothers immunized with the same dose of HSA-CFA (P less than 0.0005). In contrast, when 25 mg of MRAG-CFA were used to immunize the mothers, the lack of DTH response to MRAG was observed in male and female offspring (P less than 0.0005 for both groups). In all cases, the DTH response to HSA was positive. The spleen mononuclear (SpM) cells transferred from rats unresponsive to MRAG to normal rats 24 h before the immunization with MRAG-CFA and HSA-CFA did not suppress the immune response whereas transference of SpM cells from suppressed animals to animals previously immunized depressed the DTH response to MRAG (suppression of the expression). The response to HSA was not affected. We can conclude that the suppression is antigen specific. PMID- 2600930 TI - ELISA test for the detection of an immunological blocking factor in human pregnancy serum. AB - We have previously shown that progesterone-treated lymphocytes of healthy pregnant women can produce a 34 kDa protein, progesterone-induced blocking factor (PIBF) capable of blocking lymphocyte function in vitro. Lymphocytes of women with idiopathic threatened pre-term delivery failed to produce this factor. On the assumption that the PIBF appears in the serum of healthy pregnant women but not in that of women at risk for immunologically based abortion of pre-term delivery, an ELISA has been designed for detecting the blocking factor in serum samples. Sera obtained at the time of delivery, as well as those from women with pre-term deliveries or miscarriages, contained significantly less PIBF than sera of 209 healthy pregnant women. Data obtained by testing sera of women at 16 weeks gestation whose pregnancies ended in spontaneous abortion showed that the predictive value of the test depended on the time interval between blood sampling and the onset of abortion. In 11 of 13 women with uterine contractions the outcome of pregnancy was predictable by normal or lower than normal levels of PIBF in the sera taken at the time the symptoms were presented. The data suggest that determination of PIBF in pregnancy serum might contribute to the diagnosis of immunologically bases pre-term disruption of pregnancy. PMID- 2600932 TI - Aromatase activity in cultured ovaries from neonatally thymectomized mice with ovarian dysgenesis. AB - The autoimmune oophoritis resulting from thymectomy at 3 days of age (Tx-3) in B6A female mice is characterized by dysgenic ovaries and circulating auto antibodies against the oocyte (AOA). Dysgenesis of the ovaries starts around 24 days of age with a decline in numbers of the oocytes and follicles and is accompanied by lymphocytic infiltration. By 60 days of age the ovarian dysgenesis (OD) is complete with a preponderance of interstitial cells associated with elevated levels of testosterone (T). From 60-120 days of age the ovaries become progressively smaller in size and T levels rise. Since ovarian interstitial cells can produce T, assessment of aromatase activity was determined using cultured ovaries from 20-, 30-, 60-, 90- and 120-day-old mice. Similar or enhanced ability in aromatizing T to estradiol-17 beta (E2) was demonstrated by the ovaries from all Tx-3 mice compared with those from intact mice. At 30 and 60 days of age Tx-3 mice had increased circulating levels of E2 then the levels of E2 returned to those of intact mice at 90 and 120 days of age. The results indicate that the ovaries in Tx-3 mice may have an ability to aromatize T to E2 in culture, but apparently are not doing so at 90 and 120 days of age in situ. Further, ovaries of Tx-3 animals are able to aromatize T to E2 in the absence of organized follicular cells. These abnormal responses of ovarian hormones clearly demonstrate that the presence of AOA have a damaging effect on the endocrine activity as well as the morphology of the ovary. PMID- 2600933 TI - Villitis in normal term human placentae: frequency of the lesion determined by monoclonal antibody to HLA-DR antigen. AB - Chronic villitis is a placental lesion of unestablished etiology. It is characterized by destruction of chorionic villi with a mononuclear infiltrate and focal areas of fibrinoid necrosis. The lesion frequently is seen in normal placentae, yet more lesions have been reported in placentae from abnormal pregnancies. We measured the extent of villitis in 25 normal term placentae by using both light microscopy and immunocytology for class II (HLA-DR) antigens of the major histocompatibility complex. HLA-DR antigens were found to be characteristic of villitis areas. Normal placentae showed striking variations in the incidence of villitis, but these variations did not correlate with clinical outcome. PMID- 2600934 TI - Peripheral large granular lymphocytes in normal pregnant and postpartum women: decrease in late pregnancy and dynamic change in the puerperium. AB - Large granular lymphocytes (LGLs) have a variety of cytotoxic activities of NK, K and cytotoxic T lymphocytes, suggesting that their morphology is indicative of lytic function. In non-pregnant normal control women (n = 48), the number of LGLs was 0.30 +/- 0.14 x 10(9)/l and the proportion of LGLs in their peripheral lymphocyte fraction was 14.0 +/- 5.4%. The number and proportion of LGLs were significantly decreased in the third trimester of pregnancy (n = 32; 0.19 +/- 0.08 x 10(9)/l, P less than 0.01, and 11.7 +/- 3.8%, P less than 0.05), although an unexpected increase in the proportion of LGLs was observed in the first trimester of pregnancy (n = 24; 17.5 +/- 6.5%, P less than 0.05). After delivery, the number and proportion of LGLs increased rapidly to restore the non-pregnant levels and showed a marked increase in LGL count 4 months postpartum. These data suggest that lymphocyte-mediated cytotoxicity decreases in late pregnancy and increase dynamically after delivery to restore the non-pregnant state. PMID- 2600935 TI - Expression of a cell surface antigen with potential Ca2+-sensor/receptor function in rat placenta and uterus. AB - The reactivities of monoclonal anti-parathyroid antibodies identifying a cell surface 'calcium sensing' mechanism were investigated in the placenta and uterus of the pregnant rat. The rat placenta showed positively stained cells at the end of pregnancy. Staining was confined exclusively to the columnar epithelial cells lining the sinuses of Duval. In the uterus, positive staining of the epithelium lining the uterine lumen was obtained exclusively prior to and during implantation. PMID- 2600937 TI - Rethinking rheumatic disease therapy. PMID- 2600936 TI - Purification of low molecular weight forms of seminal vesicle specific antigen by immunoaffinity chromatography on bound monoclonal antibody MHS-5. AB - A method has been developed for purification of the low molecular weight forms of seminal vesicle specific antigen (SVSA). Pooled, liquified seminal fluid was fractionated by CM cellulose chromatography followed by two cycles of monoclonal antibody affinity chromatography. Analysis of the final product shows microheterogeneity of the purified immunoreactive peptides in the range of 9-12 kDa. In one run, from 1138 mg starting material, 2.78 mg of SVSA protein was obtained, a recovery of 0.24% of the total protein in the starting material. The purified material as assessed by scanning densitometry of Coomassie stained gels is 99% pure. These findings indicate that the three-step chromatographic method is useful for purifying the low molecular weight forms of SVSA. PMID- 2600938 TI - Elevation of a tumor associated antigen CA 19-9 levels in patients with rheumatic diseases. AB - We investigated the incidence and characteristics of an elevated tumor associated antigen CA 19-9 in patients with rheumatic diseases. Serum concentration of CA 19 9 was increased in 13 of 39 patients (33.3%) with definite or classical rheumatoid arthritis (RA), in 6 of 19 patients (31.6%) with systemic lupus erythematosus (SLE), in 3 of 9 patients (33.3%) with progressive systemic sclerosis (PSS) and in 9 of the other 35 patients (25.7%). Malignant neoplasm was not detected in any of the patients with rheumatic diseases. Pretreatment of mouse serum with patients' sera did not reduce the measured CA 19-9 values obtained by the conventional assay. The CA 19-9 antigen found in sera from patients with RA was present in a non-IgG fraction, and had the same molecular weight as that in one patient with pancreatic cancer, as determined by gel filtration. These results demonstrated that serum CA 19-9 levels were increased in some patients with rheumatic diseases. PMID- 2600939 TI - A longitudinal study of the leukocyte protein L1 as an indicator of disease activity in patients with rheumatoid arthritis. AB - L1 is a major granulocyte and monocyte protein. It is released during leukocyte activation, and the plasma level is thought to reflect the inflammatory activity. Fifteen patients with classical or definite rheumatoid arthritis were examined monthly during one year. The laboratory tests included L1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), orosomucoid, haptoglobin, ceruloplasmin, alpha 1-antitrypsin, immunoglobulins and blood cell counts. The clinical tests included articular index, grip strength, morning stiffness and pain. The L1 protein was found to have highly significant correlations (p less than 0.0001) with orosomucoid (r = 0.86), CRP (r = 0.79), ESR (r = 0.78), haptoglobin (r = 0.75), alpha 1-antitrypsin (r = 0.63) and ceruloplasmin (r = 0.44). Significant correlation was also found between L1 and IgA. None of the laboratory variables showed significant correlation with pain, but when they were correlated with articular index, grip strength and morning stiffness, L1 was found to have the highest average correlation coefficient (p less than 0.0001). PMID- 2600940 TI - Bone remodeling and osteophyte formation after remission of rheumatoid arthritis. AB - Bone remodeling and osteophyte formation rarely take place in active rheumatoid arthritis (RA). To determine if disease inactivation leads to their occurrence, we studied 38 patients with RA whose disease had gone into drug induced remission. We looked for osteophytes at the metacarpophalangeal (MCP) joints in roentgenograms taken before and after remission, and correlated their presence to that of osteoarthritis of the distal interphalangeal (DIP) joints. There were 21 patients with RA who had a median of 3 (range 1-8) osteophytes in their "remission" films which were rarely present in their "activity" films (p less than 0.0001). The osteophytes were frequently symmetrical and most often located (41%) at the third MCP joint. In addition, we observed a peculiar remodeling of the styloid process in 13 patients, 9 of whom had developed MCP joint osteophytes. There were no other detectable differences between patients who had MCP joint osteophytes and those who did not. Presence of osteoarthritis at the DIP joints did not correlate with development of osteophytes. We were able to classify the MCP osteophytes into 3 types on the basis of their shape: hook-like that were most frequently bilateral and situated on the radial aspect of the metacarpal side of the joint, beak-like that were most often found at the ulnar aspect of the phalangeal side, and nipple-like which occurred equally on either sites. These differences in distribution indicate that they are not stages of the same process. Our findings indicate that paraarticular bone remodeling occurs upon remission of RA, even in joints where osteoarthritis is unusual. Its shape and location may depend on both their site and the mechanism of joint damage. PMID- 2600941 TI - Discriminant and convergent validity of self-report measures of affective distress in patients with rheumatoid arthritis. AB - The discriminant and convergent validity of several self-report measures of affective distress commonly administered to patients with rheumatoid arthritis (RA) were examined. Fifty-two patients with RA completed the Arthritis Helplessness Index, the Beck Depression Inventory, Spielberger's State Anxiety and Trait Anxiety Inventories, and the Arthritis Impact Measurement Depression and Anxiety Scales. Correlational and factor analyses revealed that the measures of anxiety and depression demonstrated adequate convergent validity but poor discriminant validity. Our results suggest that these measures index a general feeling of distress rather than discrete affective difficulties. The ability of these measures to assess separate problems of anxiety and depression among RA patients is questioned. PMID- 2600942 TI - Treatment of refractory ischemic skin ulcers in patients with Raynaud's phenomenon with PGE1 infusions. AB - Prostaglandin E1 (PGE1) is a potent vasodilator and inhibitor of platelet aggregation. We administered 20 PGE1 infusions to 12 patients with severe Raynaud's phenomenon, associated with refractory ischemic skin ulcers. There was symptomatic improvement following 17 of the 20 infusions, while 35 of the 65 ischemic ulcers healed between 2-6 weeks following treatment. The beneficial effects persisted for between 1-18 months. While the treatment was well-tolerated in most patients, the procedure is not without risks. On the basis of this retrospective study, a trial of PGE1 infusion is recommended in the treatment of patients with ischemic skin ulcers, which have been refractory to other treatment modalities. PMID- 2600944 TI - Retrospective analysis of 376 irradiated patients with ankylosing spondylitis and nonirradiated controls. AB - Controlled, prospective studies of deep X-ray therapy (DXT) in ankylosing spondylitis (AS) are lacking. We studied a self-help group of 1702 consecutive individuals with AS. Of these, most of whom were men, 376 (22%) had undergone DXT. An attempt was made to select a control for each. Because of the difference in ages at onset, 100 treatment recipients were matched with 100 controls (mean ages 44.5 years and 44.7 years, respectively). The mean Ankylosing Spondylitis Assessment Questionnaire disability score (range 0-8) was worse for the DXT group (5.5 vs 4.8 for controls: p less than 0.0001) and most components of the Arthritis Impact Measurement Scales showed a poorer outcome for those irradiated. Thus, 22% of nationwide AS sufferers had irradiation. This group could also have had more severe disease at the outset. At review, somewhat fewer of the irradiated group were taking NSAID. Although irradiation may have favorably affected the course of these patients our data do not support the use of irradiation except in exceptional cases. PMID- 2600943 TI - Cytokines and immunoglobulin in rheumatic heart disease: production by blood and tonsillar mononuclear cells. AB - Rheumatic fever and rheumatic heart disease are considered to result from abnormal immune responses after Group A streptococcal pharyngitis. Production of interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF), interleukin 2 (IL-2) and immunoglobulin (Ig) by blood and tonsillar mononuclear cells from rheumatic or healthy children was measured after stimulation in vitro by pokeweed mitogen (PWM) or the streptococcal extracellular product, blastogen A (BLA). Tonsillar cells from patients with rheumatic heart disease produced significantly less IL 1, TNF, IL-2, and Ig than control tonsillar cells. In contrast, blood mononuclear cell cultures from rheumatic children produced more TNF and IL-2 than controls. Our findings suggest that abnormal regulation of cytokine and Ig production may contribute to the pathogenesis of acute rheumatic fever and rheumatic heart disease. PMID- 2600945 TI - Juvenile rheumatoid arthritis inflammatory eye disease. Parasitization of ocular leukocytes by mollicute-like organisms. AB - Patients with juvenile rheumatoid arthritis (JRA) commonly develop serious eye disease, particularly chronic uveitis. Most chronic uveitis is idiopathic. Mollicute-like organisms (MLO) were recently reported to be a common cause of chronic uveitis. MLO are pathogenic intracellular cell wall deficient bacteria. No culture system exists for MLO. Disease diagnosis is based on detection using a transmission electron microscope. Uveitis producing MLO are detectable within parasitized intraocular leukocytes. They appear as intracytoskeletal 0.005-0.01 micron diameter filaments and undulating pleomorphic 0.01-1.0 micron tubulospherical bodies. This report describes MLO parasitized lesional leukocytes in the inflammatory eye disease of 5 patients with JRA. Our results indicate that MLO caused the uveitis of these patients. The significance of these findings and rifampin treatment of MLO disease are discussed. PMID- 2600946 TI - Users of a public arthritis information service and their needs. AB - Brief interviews were conducted with 1670 users of the Arthritis Information Service of Alabama, a statewide toll-free telephone information service. The results showed the service users were significantly (p less than 0.01) different from both the adult population and from the estimated symptomatic population of the service area. Users tended to be female, symptomatic, white, older, and better educated than the adult population. The most frequent category of need was emotional support, followed by referral, symptom/test explanation, treatment explanation, self-help method, medication, and physician-patient communication. Informational needs were significantly related to the gender, age, and the reported diagnoses of the user. Our results suggested that telephone services for health promotion may need to make special efforts to reach nonwhite and less educated persons and to provide emotional support. PMID- 2600947 TI - Agranulocytosis and liver damage associated with pyrazinobutazone with evidence for an immunological mechanism. AB - Agranulocytosis and liver injury is described in a patient with Reiter's syndrome of 3 years duration who received pyrazinobutazone for 6 weeks before the development of the clinical picture reported. Other causes of agranulocytosis and hepatic damage were excluded and a lymphocyte transformation test to the drug revealed significant lymphocyte proliferation in response to the drug. This suggests a hypersensitivity reaction as the mechanism for this previously unrecognized association of adverse effects to pyrazinobutazone. PMID- 2600948 TI - Systemic lupus erythematosus and tetrasomy-X. AB - An 18-year-old woman with tetrasomy-X (48,XXXX karyotype) who developed systemic lupus erythematosus is described. This is, to our knowledge, the first recorded case of this association. The occurrence of autoimmune disorders in patients with chromosomal aberrations is discussed. PMID- 2600950 TI - Severe immune thrombocytopenia and the development of skin infarctions in a patient with an overlap syndrome. AB - A 49-year-old woman with clinical features of systemic lupus erythematosus, systemic sclerosis, Sjogren's and the antiphospholipid syndromes developed severe immune thrombocytopenia and skin infarctions. Both complications responded to immunosuppressive agents. PMID- 2600949 TI - Immunological abnormalities in autoimmune chronic active hepatitis. AB - Autoimmune chronic active hepatitis is often associated with clinical and laboratory features that resemble those observed in systemic lupus erythematosus (SLE). We describe a 24-year-old woman with autoimmune chronic active hepatitis who was studied for serologic markers of autoimmunity and for immune clearance in terms of in vivo Fc receptor function. A markedly depressed immune clearance and splenic uptake of radiolabelled and IgG coated autologous erythrocytes was observed. The magnitude of this defect equaled or exceeded the most severe defects seen in a group of patients with SLE. This phenomenon was associated with markedly depressed serum C4 levels, a variably positive Sm antibody, and normal circulating immune complex concentrations. In addition, many clinical extrahepatic manifestations meeting criteria for classifying SLE were present. These findings further support the concept of autoimmune chronic active hepatitis and SLE being part of spectrum of overlapping autoimmune diseases. PMID- 2600951 TI - An unusual presentation of Lyme arthritis. AB - A patient eventually found to have Lyme arthritis presented with a symmetrical polyarthritis clinically resembling both rheumatoid arthritis and an enthesopathy but with a negative RA latex test. A history of tick bite was obtained only on followup questioning. Her Lyme serology was positive and her response to antibiotic treatment was complete. PMID- 2600952 TI - Detection of Borrelia in the synovial tissue from a patient with Lyme borreliosis by electron microscopy. AB - We describe a woman who suffered for several years from joint pain with subsequent development of arthritis of her left knee. Because of these symptoms she was subjected to repeated studies including arthroscopy and menisectomy. IgG antibodies to Borrelia determined by ELISA were reported to be present and showed an increase of IgG titer to 1:1024. Histology from the last synovial biopsy disclosed only evidence of a nonspecific synovitis and marked inflammatory infiltration with lymphocytes and plasma cells. Borrelia-like structures were detected electron microscopically on semithin Epon sections from the lumen of the strongly infiltrated blood capillary. In our case the detection of Borrelia indicated the basis for increase of antibodies against Borreliae. It established the correct diagnosis and led to specific therapy of the disease after several years of unsuccessful attempts to control it. PMID- 2600953 TI - Elevated urinary ferritin in lupus nephritis. PMID- 2600955 TI - Hepatic arteritis in Behcet's disease. PMID- 2600954 TI - Pulse methylprednisolone therapy reduces monocyte IL-1 production ex vivo. PMID- 2600956 TI - Chronic inflammatory polyneuropathy complicating SLE: successful treatment with monthly oral pulse cyclophosphamide. PMID- 2600957 TI - Polymyositis and non-Hodgkin's lymphoma. PMID- 2600958 TI - Production of "virulence factors" by "epidemic" methicillin-resistant Staphylococcus aureus in vitro. AB - The production of virulence factors was determined quantitatively for clinical isolates of methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) strains of Staphylococcus aureus from The London Hospital. The examined factors were: production of enterotoxins A, B, C and D, determined by ELISA; quantitation and differentiation of the membrane-damaging alpha, beta, gamma and delta haemolysins; and coagulase production determined by a chromogenic assay. Enterotoxin A was produced by MRSA but not by MSSA. All the strains produced haemolysins alpha, gamma and delta at similar levels, but MRSA produced significantly more coagulase than MSSA. MRSA and MSSA were compared in a phagocytosis assay but there was no difference between the phagocytosis of MRSA and MSSA by human polymorphonuclear leucocytes. These findings indicate that MRSA from The London Hospital is at least as well equipped to cause disease as other isolates of S. aureus, and probably better equipped than most hospital isolates of MSSA. PMID- 2600959 TI - Cultural and electronmicroscopic studies of the effect of penicillin on tolerant oral streptococci. AB - Penicillin-tolerant and -sensitive strains of oral streptococci were treated with penicillin to determine the production of a post-antibiotic effect (PAE). No PAE was seen with any of the S. sanguis strains tested but most strains of the other oral streptococcal species produced a PAE. Cultures on nitrocellulose filters treated with penicillin were examined by scanning electronmicroscopy and showed that tolerant and sensitive strains lost the ability to adhere to the filter after application of antibiotic. When the filters were treated with beta lactamase, before processing for microscopy, the tolerant strains but not the sensitive ones recovered and grew in a confluent lawn similar to the control cultures that had not received antibiotic. Transmission electronmicroscopic examination of similarly treated cultures produced comparable results. Bizarre morphological changes were a feature of the tolerant strains of S. sanguis. PMID- 2600960 TI - Membrane and junctional properties of dissociated frog lens epithelial cells. AB - Individual cells and cell pairs were isolated from frog lens epithelium. Individual cells were whole cell voltage clamped and the current-voltage relationship was determined. The cells had a mean resting voltage of -54.3 mV and a mean input resistance of 1.4 G omega. The current-voltage relationship was linear near the cell resting voltage, but showed decreased resistance with large depolarization or hyperpolarization. Junctional currents between pairs of cells were recorded using the dual whole cell voltage-clamp technique. The corrected junctional resistance was 15.5 M omega (64.5 nS). The junctional current-voltage relationship was linear. A combination of ATP and cAMP, in the electrodes, stabilized junctional resistance. Currents recorded when uncoupling was nearly complete, showed evidence of single connexion gating events. A single-channel conductance of about 100 pS was prominent. Dye spread between isolated cell pairs was demonstrated using Lucifer Yellow CH in a whole cell configuration. Photodamage to the cells due to the dye was apparent. Dye loaded cells, in the presence of exciting light, showed decreased resting voltages, decreased input resistances and morphological changes. Glutathione (20 mM) delayed this damage. PMID- 2600961 TI - Electrophysiological investigation of the amino acid carrier selectivity in epithelial cells from Xenopus embryo. AB - The electrical responses induced by external applications of neutral amino acids were used to determine whether different carriers are expressed in the membrane of embryonic epithelial cells of Xenopus laevis. Competition experiments were performed under voltage-clamp conditions at constant membrane potential. Gly, L Ala, L-Pro, L-Ser, L-Asn and L-Gln generate electrical responses with similar apparent kinetic constants and compete for the same carrier.They are [Na]o and voltage-dependent, insensitive to variations in [Cl]o and [HCO3]o, inhibited by pHo changes, by amiloride and, for a large fraction of the current, by MeAIB. The increase in [K]o at constant and negative membrane potential reduces the response, whereas lowering [K]o augments it. L-Leu, L-Phe and L-Pro appear to compete for another carrier. They generate electrogenic responses insensitive to amiloride and MeAIB, as well as to alterations of membrane potential, [Na]o and [K]o. Lowering [Cl]o decreases their size, whereas increasing [HCO3]o at neutral pHo increases it. It is concluded that at least two and possibly three transport systems (A, ASC and L) are expressed in the membrane of the embryonic cells studied. An unexpected electrogenic character of the L system is revealed by the present study and seems to be indirectly linked to the transport function. L-Pro seems to be transported by system A or ASC in the presence of Na and by system L in the absence of Na. MeAIB induces an inward current. PMID- 2600962 TI - Social support and substance use in early adolescence. AB - In data from two cohorts of urban adolescents, measures of coping through support seeking from peers and adults were related to indices of cigarette smoking and alcohol use. Peer support was positively related to substance use, whereas parental and other adult support were inversely related to substance use. Peer support had interactive relationships (positively weighted) with peer smoking and alcohol use: support had no effect when there were no friends who smoked/drank but had an increasingly greater effect for higher levels of peer smoking/drinking. Adult support had a similar (negatively weighted) interactive effect in relation to peer smoking and alcohol use. Peer and adult support interacted, with an increasingly greater effect of peer support on substance use for subjects with lower levels of adult support. Interactions with gender indicated peer support more strongly related to substance use for females than males. Implications for the theory of social networks and the prevention of substance use are discussed. PMID- 2600963 TI - Attitudes of cancer: psychometric properties of fighting spirit and denial. AB - Higher rates of recurrence-free survival at 5- and 10-year follow-up have been reported for breast cancer patients who initially responded to cancer with attitudes of "fighting spirit" or denial. We report here a factor analytic attempt, utilizing questionnaire data, to objectify these attitudes. A reliable factor structure replicated in breast and mixed cancer samples, yielding three factors: (1) Fighting Spirit or belief in the ability to fight back, conquer, and recover from cancer; (2) Information-Seeking behavior; and (3) Denial. Adequate 1 month test-retest correlations were obtained for Fighting Spirit and Information Seeking factor scores. A pattern of differential correlations with other measures (affect, coping, and optimism) distinguished Fighting Spirit and Information Seeking. The Denial factor appeared to be less stable and did not correlate significantly with other measures. PMID- 2600964 TI - The importance of chronicity and controllability of stress in the context of stress-illness relationships. AB - The primary purpose of the present study was to increase our understanding of the roles of chronicity and controllability in the measurement of stress within the context of stress-illness relationships. Controllability and chronicity were assessed directly using a modified version of the Everyday Problems Scale. In addition to this scale, measures of depression, psychosomatic symptoms, and social support were administered to 128 women and 100 men. The results indicated that, for both men and women, the number of stressors was the best single predictor of symptoms. However, for women, chronicity and controllability of the stressors accounted for a significant amount of the variance in health outcomes over and above that accounted for by the number of stressors endorsed; for men, the addition of neither chronicity nor controllability consistently increased the strength of the association. While available social support was not found to influence the stress-illness relationships, greater willingness to utilize social support was associated with lower levels of depression. PMID- 2600965 TI - Reactions of dysmenorrheic and nondysmenorrheic women to experimentally induced pain throughout the menstrual cycle. AB - It has been proposed that dysmenorrheic women have a heightened pain sensitivity compared to nondysmenorrheic women, although previous studies investigating this hypothesis have yielded conflicting results. This study investigated the pain sensitivity of nondysmenorrheic women and of women suffering from spasmodic, congestive, and combined dysmenorrhea, across three phases of the menstrual cycle: premenstrual, menstrual, and intermenstrual. No interaction between type of dysmenorrhea and menstrual phase was found for either pain threshold or pain tolerance, using three procedures of experimentally induced pain. On a self report measure of pain, however, the congestive and combined dysmenorrheics reported the highest degree of pain and distress, especially during the premenstrual and menstrual phases; nonsufferers reported the lowest degree and were stable across phases. PMID- 2600966 TI - Psychophysiological responses to stress in patients with myofascial pain dysfunction syndrome. AB - The hypothesis was tested that patients diagnosed with myofascial pain dysfunction (MPD) syndrome display a stereotypic response to stress via increased activity in the facial muscles. Twenty MPD patients and 20 matched control subjects were seated and exposed to affectively neutral, then stressful, then affectively neutral film clips. During film viewing, heart rates and skin conductance levels were recorded along with bilateral EMG activity from the frontalis, temporalis, and masseter muscles and unilateral EMG activity from the forearm extensor. While both groups showed facial EMG responses to the stressor, MPD patients showed lower heart-rate and skin-conductance responses to experimental stress than did normals and a differentially higher frontalis EMG response. MPD patients also showed higher resting EMG levels than did normals at four of six facial muscle sites. PMID- 2600967 TI - Conserved sequence elements upstream and downstream from the transcription initiation site of the Caulobacter crescentus rrnA gene cluster. AB - The nucleotide sequence and in vivo transcription start sites for rrnA, one of the two rRNA gene clusters of the eubacterium Caulobacter crescentus, have been determined. Two transcription start sites, a major and minor, for the rRNA gene cluster are located more than 700 nucleotides upstream from the 16 S rRNA gene. Transcription was detected from only the major start site in swarmer cells. But after the swarmer-to-stalked cell transition, transcription was detected from both rRNA start sites and continued throughout the developmental cell cycle when cells were grown in minimal medium. On the other hand, transcription from only the major start site was detected in cells growing in a complex medium. A small open reading frame was found upstream from the rRNA gene transcription start sites and was followed by an inverted repeat sequence. No sequence homology was found between the major rRNA gene transcription start site and the Escherichia coli sigma 70 promoters or the consensus sequence elements reported for C. crescentus fla promoters. However, there were two areas of homology when the major rRNA gene promoter was compared to the nucleotide sequence of the C. crescentus trpFBA promoter. There was a 12 nucleotide sequence centered around the -10 region of both promoters that was closely homologous. In addition, immediately downstream from the transcription start there was a sequence element that was identical in both promoters. These nucleotide sequence elements were not in the temporally expressed fla promoters of C. crescentus. PMID- 2600968 TI - Chromosomal recombination and breakage associated with instability in mouse centrometric satellite DNA. AB - A mouse L cell line containing the centromeric insertion of herpes thymidine kinase genes (tk) was previously shown to undergo a high frequency of DNA rearrangement at the site of tk insertion. Analysis of TK- revertants had demonstrated that DNA rearrangements were usually associated with DNA deletion and were always mediated by intrachromosomal recombinations. In this study, we further analyzed several TK+ subclones to examine the mode of DNA rearrangements in the absence of negative selection pressure. In two clones, LC2-3F and LC2 3E17, rearrangements were accompanied by DNA amplification and were mediated by intrachromosomal recombination. In subclone LC2-3E17-19, we further detected perturbations in the pattern of centromeric heterochromatization. This was associated with chromosome instability, as evidenced by chromosome breakage at the centromere. The analysis of three other sibling clones, LC2-3, LC2-6 and LC2 15, further suggests that reciprocal recombination events may play a role in such centromeric rearrangements. These results suggest that DNA rearrangements in the centromere may be mediated by a number of different mechanisms, and generally do not affect chromosome stability except when accompanied by changes in the pattern of heterochromatization. PMID- 2600969 TI - Pleomorphism in type I collagen fibrils produced by persistence of the procollagen N-propeptide. AB - The assembly of type I collagen and type I pN-collagen was studied in vitro using a system for generating these molecules enzymatically from their immediate biosynthetic precursors. Collagen generated by C-proteinase digestion of pC collagen formed D-periodically banded fibrils that were essentially cylindrical (i.e. circular in cross-section). In contrast, pN-collagen generated by C proteinase digestion of procollagen formed thin, sheet-like structures that were axially D-periodic in longitudinal section, of varying lateral widths (up to several microns) and uniform in thickness (approximately 8 nm). Mixtures of collagen and pN-collagen assembled to form a variety of pleomorphic fibrils. With increasing pN-collagen content, fibril cross-sections were progressively distorted from circular to lobulated to thin and branched structures. Some of these structures were similar to fibrils observed in certain heritable disorders of connective tissue where N-terminal procollagen processing is defective. The observations are considered in terms of the hypothesis that the N-propeptides are preferentially located on the surface of a growing assembly. The implications for normal diameter control of collagen fibrils in vivo are discussed. PMID- 2600970 TI - Crystallographic study of one turn of G/C-rich B-DNA. AB - The DNA decamer d(CCAGGCCTGG) has been studied by X-ray crystallography. At a nominal resolution of 1.6 A, the structure was refined to R = 16.9% using stereochemical restraints. The oligodeoxyribonucleotide forms a straight B-DNA double helix with crystallographic dyad symmetry and ten base-pairs per turn. In the crystal lattice, DNA fragments stack end-to-end along the c-axis to form continuous double helices. The overall helical structure and, notably, the groove dimensions of the decamer are more similar to standard, fiber diffraction determined B-DNA than A-tract DNA. A unique stacking geometry is observed at the CA/TG base-pair step, where an increased rotation about the helix axis and a sliding motion of the base-pairs along their long axes leads to a superposition of the base rings with neighboring carbonyl and amino functions. Three-center (bifurcated) hydrogen bonds are possible at the CC/GG base-pair steps of the decamer. In their common sequence elements, d(CCAGGCCTGG) and the related G.A mismatch decamer d(CCAAGATTGG) show very similar three-dimensional structures, except that d(CCAGGCCTGG) appears to have a less regularly hydrated minor groove. The paucity of minor groove hydration in the center of the decamer may be a general feature of G/C-rich DNA and explain its relative instability in the B form of DNA. PMID- 2600971 TI - Structure of [4Fe-4S] ferredoxin from Bacillus thermoproteolyticus refined at 2.3 A resolution. Structural comparisons of bacterial ferredoxins. AB - The structure of a low-potential ferredoxin isolated from Bacillus thermoproteolyticus has been refined by a restrained least-squares method. The final crystallographic R factor is 0.204 for 2906 reflections with F greater than 3 sigma F in the 6.0 to 2.3 A resolution range. The model contains 81 amino acid residues, one [4Fe-4S] cluster, and 59 water molecules. The root-mean-square deviation from ideal values for bond lengths is 0.018 A, and the mean coordinate error is estimated to be 0.25 A. The present ferredoxin is similar in the topology of the polypeptide backbone to the dicluster-type ferredoxins from Peptococcus aerogenes and Azotobacter vinelandii, but has considerable insertions and deletions of the peptide segments as well as different secondary structures. Although all but the C-terminal C zeta atoms of P. aerogenes ferredoxin superpose on the C alpha atoms of A. vinelandii ferredoxin, only 60% superpose on the C alpha atoms of B. thermoproteolyticus ferredoxin, with a root-mean-square distance of 0.82 A for each pair. The conformations of the peptide segments surrounding the [4Fe-4S] clusters in these three ferredoxins are all conserved. Moreover, the schemes for the NH...S hydrogen bonds in these ferredoxins are nearly identical. The site of the aromatic ring of Tyr27 in B. thermoproteolyticus ferredoxin is close spatially to that of Tyr28 in P. aerogenes ferredoxin with reference to the cluster, but these residues do not correspond in the spatial alignment of their polypeptide backbones. We infer that in monocluster-type ferredoxins, the side-chain at the 27th residue has a crucial effect on the stability of the cluster. Of the four cysteine residues that bind to the second Fe-S cluster in the dicluster-type ferredoxins, two are conserved in the monocluster-type ferredoxins from Desulfovibrio gigas. D. desulfuricans Norway, and Clostridium thermoaceticum. The tertiary structure of B. thermoproteolyticus ferredoxin suggests that in such monocluster-type ferredoxins these two cysteine residues, which in it correspond to Ala21 and Asp53, form a disulfide bridge. PMID- 2600972 TI - DNA B to D transition can be explained in terms of hydration economy of the minor groove atoms. AB - Adjacent phosphate oxygen atoms in A and Z-DNA are located much closer together than in the B form and can be hydrated more economically due to the formation of water bridges between them, whereas in the B form phosphates are hydrated individually. This principle of hydration economy of phosphate groups discovered by Saenger and colleagues could not be applied to the B-D transition, which, like the B-A and B-Z transitions, occurs in a situation of water deficiency, because the distances between adjacent phosphates of individual polynucleotide chains in the D form are not much different from B-DNA. It follows from our calculations of B and D-DNA accessibility to solvent performed by the method of Lee & Richards, and from a simulation of solvent structure near DNA, that there is an economy of hydration only for the minor groove atoms. This feature and some experimental data can explain why only a limited range of sequences consisting of A.T or I.C pairs undergo the transition to the D form. The conformational transition in DNAs with such sequences to a poly[d(A]).poly[d(T])-like conformation (Bh-DNA), which is accompanied by a narrowing of the minor groove, can be explained in the same way. Calculations suggest that in the D-form minor groove of different A-T or I-C DNAs there is a double-layer hydration spine similar to that observed by Drew & Dickerson in the A-T tract of the d(C-G-C-G-A-A-T-T-C-G-C-G) dodecamer. The B-D and B-Bh transitions in A + T-rich DNAs can have biological implications, e.g. they can facilitate DNA bending upon the interaction with proteins. PMID- 2600973 TI - Developmental morphology of the solum nasi in the mouse lemur (Microcebus murinus). AB - The solum nasi of Microcebus murinus is characterized by the presence of a zona annularis, continuity between the anterior transverse lamina and the paraseptal cartilage, a continuous paraseptal cartilage, a palatine cartilage and a posterior transverse lamina. It lacks a fibula reuniens and possibly a cartilage of the nasopalatine duct as well as a palatine papillary cartilage. The morphology in M. murinus closely resembles that seen in Tupaia and Galago. This affinity results from the retention of primitive traits. However, Galago is reported to lack a zona annularis, thus displaying a specialization not shared with M. murinus. Therefore, the zona annularis provides a useful trait for distinguishing between the ontogenies of M. murinus and Galago. PMID- 2600974 TI - Ultrastructural features of the developing eosinophils in bone marrow and spleen of the musk shrew, Suncus murinus. AB - Eosinophilopoiesis in the musk shrew, Suncus murinus, a representative of the order Insectivora, was studied by light and electron microscopy. To examine biochemical features of cytoplasmic granules, extraction with proteolytic enzymes was carried out on ultrathin sections of bone marrow. In this species, eosinophils are produced in the same manner in both spleen and bone marrow. Developing eosinophils were distinguished as belonging to four stages, recognized by ultrastructural changes in cytoplasmic organelles as well as the eosinophilic granules during maturation. Granulogenesis began by budding of vacuoles containing flocculent material from the concave face of the Golgi apparatus, in the promyelocyte to myelocyte stage. The matrix of developing granules transformed into a finely granular structure, and the large spherical granules of mature eosinophils were homogeneous without crystalline cores. It was shown by proteolytic enzyme extraction that the proteinaceous cores of mature granules were uniformly removed; there was no evidence that they contained crystalloid inclusions. These results indicate that shrew eosinophils can be regarded as cells that retain a prototype of eosinophil granules, probably like those of ancestral mammals rather than those of higher living Mammalia. PMID- 2600975 TI - Phylogenetic diversity of cellular organization in the cardia of muscoid flies (Diptera: Schizophora). AB - In each of 30 dipteran species, representing 13 acalyptrate and 7 calyptrate families, the cardia is formed from specialized cells at the junction between foregut and midgut. Foregut epithelium forms the stomodeal valve; midgut epithelium envelops the valve to form the cardia's outer wall. Cytological characteristics within these epithelia differ from region to region and from species to species. Since the cardia secretes the peritrophic membrane, cardias with diverse patterns of cellular differentiation may be expected to produce peritrophic membranes with similarly diverse properties. Close relatives often share more details of cardia structure than do distantly related taxa. Within the monophyletic Calyptratae, a common pattern of cellular differentiation includes three distinct zones of columnar midgut cells enclosing a flanged stomodeal valve. Among species in the paraphyletic Acalyptratae, midgut typically includes a single zone of tall columnar cells, while the valve may be spheroidal, cylindrical, conical, or flanged. The correlation of phylogenetic distance with divergence in cardia organization implies a strong influence of ancestry upon current structure, regardless of current diet. However, at least some of the observed diversity in cardia structure is associated with dietary divergence. Calyptrate flies with derived blood-feeding behavior display cellular differentiation that is simplified from that seen in calyptrate relatives with less specialized feeding habits. This evolutionary modification suggests that cardia organization and hence peritrophic membrane structure can adapt to dietary changes, with possible significance for the spatial organization of digestive processes and interactions with ingested microorganisms. PMID- 2600976 TI - EGF-induced neuritogenesis and correlated synthesis of plasma membrane gangliosides in cultured embryonic chick CNS neurons. AB - Epidermal growth factor (EGF), over a low range of concentrations (165-825 pM), induced neuritogenesis in post-mitotic chick CNS precursor neurons cultured in a serum-free medium, without the addition of other growth factors. Antibody to EGF blocks the neurite-promoting activity of EGF. Similarly, neuritogenesis of cultured chick CNS neurons in medium supplemented with 20% fetal bovine serum is blocked by antibody to EGF, even though serum may contain other neuronotrophic bioactive proteins and steroids. Quantitatively, the only major gangliosides of the undifferentiated post-mitotic neurons are GD3 and GD2. GD3 as well as its biosynthetic precursor, GM3, undergo active biosynthesis in serum-free medium as evidenced by their vigorous labeling by radioactive galactose supplied in the culture medium. When the undifferentiated neurons in serum-free medium are exposed to EGF, the ensuing generation of neurite plasma membrane coincides with initiation of biosynthesis of the sialosyl gangliotetraosyl ceramide species of gangliosides (GD1A, GD1B, GT1B, GQ1B). Antibody to EGF simultaneously inhibits biosynthesis of these gangliosides as well as inhibition of neuritogenesis. These findings indicate that EGF may be a primary neurite-inducing growth factor for post-mitotic embryonic CNS neurons and that gangliosides, particularly those of the sialosyl gangliotetraosyl ceramide species, characterize the plasma membrane of CNS neurons during neuritogenesis. PMID- 2600977 TI - Differential control of tryptophan hydroxylase expression in raphe and in pineal gland: evidence for a role of translation efficiency. AB - In a previous study, we characterized two tryptophan hydroxylase mRNAs (TPH mRNAs) in the pineal gland. However, we failed to detect these species in the raphe by Northern blot experiments. Here, we report by S1 nuclease analysis and in situ hybridization that these two TPH mRNAs, as well as a third species, are expressed both in pineal gland and in raphe. In both tissues, the three mRNAs are transcribed predominantly from the same promoter. Strikingly, from the results of S1 maping analysis, it was observed that the total level of TPH mRNA per tissue is at least 150 times lower in the raphe than in the pineal gland. In contrast, TPH antigen as quantified by immunoblot experiments is about threefold more abundant per raphe than per pineal gland. TPH mRNA from one raphe and one pineal gland yield in vitro about the same amount of TPH antigen, suggesting that the discrepancy in the ratios of TPH mRNA and TPH antigen between the raphe and the pineal gland results, at least in part, from a difference in the translation efficiency of TPH mRNAs in the two structures. PMID- 2600978 TI - Multiple and novel specificities of monoclonal antibodies O1, O4, and R-mAb used in the analysis of oligodendrocyte development. AB - Three monoclonal antibodies that react with antigens on the surface of developing oligodendrocytes in a stage-specific manner, O1, O4 (Sommer and Schachner, 1981), and R-mAb (Ranscht et al., 1982), have been studied with respect to their specificities for a number of purified lipids. The observed specificities were consistent regardless of how the antigens were presented to the antibodies. O1 reacted with galactocerebroside, monogalactosyl-diglyceride, and psychosine and, in addition, labeled an unidentified species in rat brain extracts. R-mAb reacted with galactocerebroside, monogalactosyl-diglyceride, sulfatide, seminolipid, and psychosine; the reaction of R-mAb with sulfatide was nearly equal to that with galactocerebroside. O4 reacted with sulfatide, seminolipid, and to some extent with cholesterol. However, oligodendrocyte progenitor cells labeling with O4 that had not yet begun to express the O1 antigen failed to incorporate 35SO4 or [3H]galactose into sulfatide or seminolipid, the syntheses of which first appear in O1-positive cells. Therefore, O4 stains, in addition to sulfatide and seminolipid, and unidentified antigen that appears on the surface of oligodendrocyte progenitors prior to the expression of sulfatide and galactocerebroside. In primary cultures of rat brain, developing O4+ oligodendrocyte progenitors stained slightly earlier with R-mAb than with O1, and thus R-mAb transiently stained a larger population of oligodendrocytes than did O1. None of the three antibodies produced a detectable reaction on Western immunoblot after separation of brain proteins on reducing gels. In conclusion, the results show that O4, R-mAb, and O1 have multiple overlapping specificities, including previously unrecognized cross-reactions. PMID- 2600979 TI - Biologic characteristics of an immunosuppressive factor derived from a human lung cancer cell line. AB - A 549, a human lung cancer cell line, spontaneously produces a tumor-derived immunosuppressive factor (TDSF) which inhibited PHA-stimulated T lymphocyte proliferation via a noncytotoxic mechanism. The inhibition increased in a dose dependent pattern. The factor also markedly suppressed production of interleukin (IL-2) by PHA-stimulated lymphocytes and IL 2-dependent proliferation of activated lymphocytes. The fact that TDSF possessed very potent inhibitive action on IL-2 is especially noteworthy if we consider the use of IL-2 as immunotherapeutic agent. The synthesis of the factor was inhibited by mitomycin C, actinomycin D and cycloheximide, indicating that the factor is a genic product of A 549 cells. The factor is chemically a protein with a molecular weight greater than 150 KD and sensitive to extremes of pH, heating to 60 degrees C and trypsin treatment. PMID- 2600980 TI - Studies on biological characteristics and modulating factors of long-term cultured bone marrow cells of a myeloma patient in vitro. AB - In the present study we cultured in vitro bone marrow cells from a patient with multiple myeloma (IgD) and researched into the modulation of supernatant media of various leukemic lines on the growth of culture cells. Cells in the cultures were studied for their morphological, biochemical, immunological and ultrastructural features. Drug sensitivity assay was also performed. The results showed that supernatant media of 6 cell lines promoted cell growth, but most remarkable stimulating activity was displayed by supernatant media from U937 and CEM. Cell cloning effect attained to more than 90%. Cultured cells possessing biological characteristics of malignant cells were probably malignant cells from B cell lineage. This study indicated that long-term cultures of marrow cells might provide a tool useful for clinical and laboratory purpose and a method for studies on pathogenesis, regulation of hematopoiesis, cell differentiation and guide-way drugs. PMID- 2600981 TI - Investigation on the inhibitory effect of tumor-derived immunosuppressive factor(s) on T lymphocyte proliferation. AB - Using five tumor cell lines, the effect of tumor-derived immunosuppressive factor(s) (TDSF) on T lymphocyte proliferation and its mechanism have been investigated. It was found that TDSF markedly inhibited PHA-stimulated T lymphocyte proliferation via a noncytotoxic mechanism. The inhibition increased in dose-dependent manner and the maximum inhibition was achieved when the factor was added at the initiation of the culture. When PBMC were preincubated with supernatants of tumor cells for 24 h, washed extensively and then cocultured with freshly prepared PBMC, similar suppressive effects were observed. The above results indicated that the activation of any suppressor cell subgroup may be one of the mechanisms of immunosuppressive action of TDSF. PMID- 2600982 TI - Normal and leukemic lymphocyte membrane fluidity and response to stimulation with ConA and PHA. AB - In our experiment, lymphocyte membrane was labeled by DPH fluorescence probe. The rate of rotation of the probe can be measured from the value of fluorescence polarization (PDPH). With this method useful information could be provided about membrane fluidity of lymphocytes. It was found that the F value (unit of lipid fluidity of membrane) of leukemic lymphocytes was obviously higher than that of normal ones. Furthermore, the F value of cultured leukemic Ts lymphocytes was the highest. In contrast with normal spleen T-lymphocytes or mixed lymphocytes, the response of malignant lymphocytes to the stimulation with ConA or PHA was reflected in the decrease of PDPH value or the increase of F value. Unexpectedly, the F value of T-lymphocytes from "615" mouse not injected with tumour cells was also higher than that of the mixed. The possibility of using the membrane fluidity as a diagnostic criterion was also discussed. PMID- 2600983 TI - Sympathetic innervation of pulmonary circulation and its role in hypoxic pulmonary vasoconstriction. AB - The purposes of this study were to localize the position of spinal center of sympathetic nerve which controls the pulmonary circulation, and to evaluate the role of pulmonary sympathetic nerve in hypoxic pulmonary vasoconstriction (HPV) in pithed rat model. The sympathetic preganglionic fibers arising from C7-T10 segments were stimulated electrically in succession. During stimulation the pulmonary vascular resistance (PVR) was increased in all segments tested, most significantly in C7-T4 (about 28% above control value), obviously higher than that in T5-T10. The higher the stimulated spinal segments, the larger the ratio of delta PVR/ delta SVR. Alveolar hypoxia (12% O2-88% N2) could induce HPV in pithed rat. In the presence of hypoxia, stimulation of T1-T3 segments caused a double increment in PVR and Ppa as compared with those during normoxia (P less than 0.05). The data show that 1) the spinal center of sympathetic nerve regulating the vasomotion of pulmonary circulation is located in the C7-T4 segments; 2) the excitation of sympathetic nervous system during hypoxia could enhance HPV. PMID- 2600984 TI - Experimental and clinical study of catecholamine-induced hypokalemia in acute myocardial infarction. AB - Adrenaline infusion to 8 rabbits led to remarkable dose-dependent hypokalemia; 2 of them died of ventricular arrhythmia (VA) with severe hypokalemia. In 6 rabbits with i.v. propranolol beforehand, no hypokalemia occurred after adrenaline infusion. Plasma catecholamines (CA) in 26 patients with AMI were greatly elevated at admission, 73% of relative hypokalemia (plasma potassium decreased to greater than or equal to 0.3 mmol/L) and a significant lowering of intraerythrocytic rate of Na/K were noted. These findings were inversely correlated with adrenaline. According to the multivariate analysis, both high level of plasma adrenaline and hypokalemia were responsible for VA in early AMI. The mechanism of CA-induced hypokalemia and its implications in AMI were discussed in detail. PMID- 2600985 TI - Hepatocyte necrosis associated with HBV marker expression and T cytotoxic cells in situ in chronic hepatitis B. AB - To explore the role of HBV antigen expression and monocyte infiltrate in situ in chronic hepatitis, HBV markers and compositions and number of monocytes in the liver of chronic hepatitis B were immunohistochemically located and identified, and correlated with hepatocyte necrosis. It was found that hepatic necrosis frequently took place in the centre or boundary of membranous HBsAg and/or HBcAg expression and the majority of monocytes accumulated in the necrotic areas showed CD8+ cell token in HBeAg-positive stage of chronic active hepatitis. On the other hand, with HBeAg positivity converted into HBeAg-negativity or anti-HBe positivity, HBV antigen expression significantly declined, CD4+ cells remarkably increased as compared to HBeAg-positive status. These findings suggest that there may be distinct pathogenesis of hepatic necrosis in different stages of chronic HBV infection. PMID- 2600986 TI - Color Doppler echocardiography, two-dimensional echocardiography and signs in diagnosis of aortic regurgitation. AB - To assess the diagnostic significance of color Doppler and two-dimensional echocardiography and signs in aortic regurgitation (AR), we studied 48 patients with AR confirmed by color Doppler. On color Doppler, an abnormal diastolic flow originating from the aortic valve was visualized in the left ventricular outflow tract in the 48 cases. The maximal regurgitant jet area was 0.8-23.3 cm2. On two dimensional echocardiography, the appearance of cardiac chamber and valves did not offer a clue to the existence of AR in 12 patients (25%). On physical examination, diastolic murmur was inaudible in 18 of 45 patients. Peripheral signs of AR were not found in 20 of 45 patients. In slight AR, signs were usually not detected. From the above we are led to conclude that of the patients with AR confirmed by color Doppler echocardiography, only 75% could be detected by two dimensional echocardiography and about 55% diagnosed by physical examination. PMID- 2600987 TI - [The supinator syndrome--an anatomical and clinical study]. AB - The interosseus posterior syndrome appears in two forms: a) the paralytical interosseus posterior syndrome, b) the painful (afferent) interosseus posterior syndrome. We report in this investigation about 12 operated patients with painful interosseus posterior syndrome. The intraoperative findings in the arcade of Frohse are compared with the findings we made at the preparation of 10 recently deceased. It was especially significant, that we found in 10 of our 12 cases intraoperatively a tendinous type of arcade. In our directioned cases we encountered this type of tendinous arcade in only 2 of 10 cases. Based on these findings we are of the opinion that the tendinous arcade of Frohse is an important factor in the development of the interosseus posterior syndrome. PMID- 2600989 TI - Opiate detoxification under general anesthesia by large doses of naloxone. AB - For opiate detoxification 6 volunteer opiate addicts were intravenously administered 10 mg naloxone within one hour while under barbiturate anesthesia. During administration of naloxone none of the patients demonstrated significant changes in the hemodynamic parameters of heart rate, mean arterial pressure, cardiac index, peripheral resistance or in the oxygen saturation. After patients awoke from anesthesia, they experienced no or only minimal withdrawal symptoms. Possible explanations for the suppression of withdrawal symptoms are discussed. PMID- 2600988 TI - Comparison of titratable acid/alkaline reserve and pH in potentially caustic household products. AB - Exposure to caustic agents is a common problem, affecting thousands of individuals annually. Despite this incidence, the factors responsible for the production of injury remain poorly defined. Although extremes of pH seem to correlate well with the production of esophageal lesions, pH alone fails to explain the damage resulting from exposure to agents with near neutral pH, such as soldering flux containing zinc chloride. We determined titratable acid/alkaline reserve (TAR) in 38 potentially caustic household agents. A subset of these products was evaluated in an in-vitro canine esophageal model to determine whether TAR correlated with esophageal injury. The results indicate that for the products evaluated TAR correlated better than pH with the production of caustic esophageal injury. PMID- 2600990 TI - Drug induced esophageal injury. AB - A 3-year-old child weighing 16 kg was given 1/2 of a Centrum Multivitamin tablet. He began choking and gagging and was taken to an emergency department. He was alert and speaking without difficulty but was drooling, gagging, coughing, and unable to swallow. He was transferred to a children's hospital where he continued to drool but had bilaterally clear and equal breath sounds and no stridor, cough, or wheeze. A lateral neck x-ray was negative. The following morning, esophagoscopy revealed tablet material identified as a granular paste at the level of the cricopharyngeus. A large amount of the paste was encountered at the crossing of the aorta where the mucosa was extremely erythematous and edematous. Smaller amounts of the paste were observed until a larger amount was found at the lower esophageal junction. The material was removed with NSS irrigation, suction, and optical peanut forceps. A significant circumferential burn was present. Repeat esophagoscopy 7 days postingestion showed mucosal edema and some scarring. Nine (9) days postingestion the child's diet was normal and he was discharged. PMID- 2600991 TI - Hyponatremia in a neonate of a cocaine abusing mother. AB - Neonatal hyponatremia can be caused by increased sodium losses, inadequate sodium intake, increased maternal or neonatal water load or by water retention secondary to excess of ADH release. Cocaine use by pregnant women has not as yet been reported to correlate with hyponatremia in the newborn infant. We present a case of an infant whose mother used cocaine regularly during the last stages of pregnancy and who developed hyponatremia in the first week of life. A mechanism is proposed and discussed. PMID- 2600992 TI - Ifosfamide encephalopathy. AB - We describe a case of reversible encephalopathy caused by the recently released anticancer drug Ifosfamide. The clinical course, role of EEG in monitoring and predicting encephalopathy, and putative mechanism of neurotoxicity is discussed. Short infusion times and/or prior CNS disease may increase the risk of encephalopathy. PMID- 2600993 TI - The effect of controls on sedatives and hypnotics on their use for suicide. AB - The requirement of prescriptions for sedatives and hypnotics in Japan led to a decrease in their use for suicide but did not lead to an increase in the use of other methods for suicide, suggesting that people did not switch methods for suicide as one method became less available. PMID- 2600994 TI - The role of Poison Control Centers in radiation accidents. AB - In the days after the nuclear reactor accident at Chernobyl (USSR) in April 1986, the Dutch Poison Control Center had to answer questions concerning possible health effects caused by (over)exposure to ionizing radiation. These questions were similar to questions asked regarding exposure to toxic agents after chemical accidents. It is obvious that the experience and practical approach of a Poison Control Center in handling toxicological problems can be used in problems concerning ionizing radiation. PMID- 2600995 TI - Intra-atrial conduction delay and fragmented atrial activity in patients with paroxysmal atrial fibrillation. AB - To examine the electrophysiologic characteristics of paroxysmal atrial fibrillation (PAF), we studied intra-atrial conduction delay and fragmented atrial activity during premature stimulation of high right atrium in the following four groups: Group I (n = 25), patients without PAF and without sick sinus syndrome (SSS); Group II (n = 22), patients with PAF but without SSS; Group III (n = 10), patients without PAF and with SSS; Group IV (n = 6), patients with PAF and SSS. Intra-atrial conduction delay was the increase in the interval (from the stimuli to the coronary sinus electrogram) observed with early premature beats greater than or equal to 20 ms compared with that of basic rhythm. Fragmented atrial activity was defined as disorganized atrial activity greater than or equal to 150% of the duration of high atrial activity of basic beats recorded. The conduction delay zone (CDZ) and fragmented atrial activity zone (FAZ) were significantly wider in Groups II, III and IV than in Group I. There were no significant differences in either CDZs or FAZs among Groups II, III and IV. Thus, the widening of CDZs and/or FAZs are characteristic of PAF and SSS. CDZ and FAZ may be good indices of development of PAF in patients without SSS. PMID- 2600996 TI - Prognosis in hypertrophic cardiomyopathy--echocardiographic follow-up and histopathological study. AB - In 30 consecutive hypertrophic cardiomyopathy (HCM) patients who eventually died and 50 who survived, morphologic and functional changes in the heart during a follow-up period of an average of 3.9 years were echocardiographically evaluated. Echocardiographic indices were compared among 5 groups of patients with HCM, consisting of 4 groups of patients who eventually died (SD: 17 patients who suffered sudden death, ED: 4 who died of embolism, HF: 4 who died of congestive heart failure, NC: 5 who died of a noncardiac event) and 1 group of patients who survived with nondilated left ventricle (S: 50 patients). These indices at the last evaluation before death were compared with histopathological findings of left ventricles in 12 autopsied patients. At the initial evaluation ED and HF patients had a larger left ventricular end-diastolic dimension (LVDd), and HF patients had a smaller percent fractional shortening (%FS) and a slower normalized rapid filling rate (nRFR: mean rapid filling rate/LVEDV) than S patients, but these indices showed no differences between SD and S patients. During follow-up, no echocardiographic indices changed in S patients, but LVDd was increased and %FS and nRFR were decreased in SD and HF patients. Mean myocyte diameter and % area of disarray showed no differences among the 4 death groups. However, compared with NC, the other 3 groups, especially HF, had larger % area of massive fibrosis. The % area of massive fibrosis was correlated with LVDd (r = 0.80, p less than 0.005), %FS (r = -0.64, p less than 0.05), and nRFR (r = -0.95, p less than 0.001) at the last evaluation. These results suggested that echocardiographic follow-up was useful in predicting the progression of the myocardial lesion and the prognosis of HCM. PMID- 2600997 TI - Prognostic significance of conduction disturbance and reduction of left precordial voltage of electrocardiogram in hypertrophic cardiomyopathy. AB - To clarify the prognostic significance of electrocardiographic changes in hypertrophic cardiomyopathy, we retrospectively evaluated serial electrocardiograms in 77 patients with hypertrophic cardiomyopathy who were followed for more than 1 year. The electrocardiographic features analyzed were conduction disturbance and left precordial QRS voltage. There were 4 sudden deaths. Various conduction disturbances appeared in 32 (44%) of the remaining 73 patients. Intraventricular conduction delay was the most common (47%). The left precordial voltage decreased in 19 (26%), increased in 3, and did not change in 51. The left ventricular end-diastolic pressure at the initial investigation was significantly higher and clinical deterioration was more frequently seen in patients with a conduction disturbance or reduction of QRS voltage than in those without these electrocardiographic changes. Also, echocardiographic analysis showed that left ventricular dimensions increased significantly (from 4.4 +/- 0.6 to 4.8 +/- 0.7 cm in end-diastole and from 2.6 +/- 0.6 to 3.1 +/- 0.8 cm in end systole; p less than 0.01, respectively) and left ventricular fractional shortening was reduced (from 41 +/- 8 to 36 +/- 11%; p less than 0.01) in the 32 patients with conduction disturbance during the follow-up period although absolute cavity size remained normal in 26 of these patients. These parameters did not change in those without conduction disturbance. Histopathological analysis of endomyocardial biopsies showed that myocardial fibrosis in the left ventricle was frequently associated with these electrocardiographic changes. However, such changes were not present in the sudden death patients. It is concluded that conduction disturbance and the reduction of QRS voltage are significant parameters which suggest a poor prognosis in patients with hypertrophic cardiomyopathy, but are not predictors of sudden death. PMID- 2600998 TI - Triphasic time dependence of prognostic markers in patients with sustained ventricular tachyarrhythmias and coronary artery disease. AB - To characterize the time dependence of prognostic markers for arrhythmia recurrence and arrhythmic death, 81 consecutive patients with documented sustained ventricular tachycardia (VT) or fibrillation (VF) and coronary artery disease (CAD) were analyzed. During follow-up, 28 patients had arrhythmia recurrence and 15 patients had sudden or arrhythmic death. Three different hazard phases were identified by fitting piece-wise exponential function curves to the distribution of both arrhythmia recurrence and sudden/arrhythmic death. An initial phase (0 to 6 months) had an arrhythmia recurrence rate of 2.1% per month; a second low-risk phase (6 to 38 months) had a rate of 0.88%; and a late high-risk phase (greater than 38 months) had a rate of 2.2%. Sudden/arrhythmic death rates in each phase were 1.1%, 0.41%, and 1.7% per month, respectively. Separate Cox regression analyses within each phase identified the following independent predictors of arrhythmia recurrence: in the early phase, ejection fraction (EF) (p = 0.033) and VT inducibility rank (p = 0.048); and in the late phase, VT inducibility rank only (p = 0.003). Likewise, independent predictors of sudden/arrhythmic death were: in the early phase, EF (p = 0.049); and in the late phase, VT inducibility rank (p = 0.008) and previous history of congestive heart failure (p = 0.032). In CAD patients with documented sustained VT/VF, the probabilities of arrhythmia recurrence and sudden/arrhythmic death each followed a similar triphasic hazard function. Highest risk occurred in the late phase and the VT inducibility rank was predictive of late phase events, while EF was a predictor of early phase events. PMID- 2600999 TI - Vectorcardiographic criteria for diagnosis of high lateral infarction--supplement for Chou's criteria. AB - The concept of high lateral myocardial infarction (HLMI) has not been clearly defined, so criteria for its vectorcardiographic (VCG) diagnosis have had no firm basis. However, we have reported that HLMI, expressed as abnormal Q waves in lead aVL on the electrocardiogram, corresponds to necrosis of the area usually supplied by the diagonal branches of the left anterior descending coronary artery. Here, we evaluated conventional VCG criteria for the diagnosis of HLMI on the basis of angiographic findings, and selected the criteria of Chou as typical. The frontal plane VCG was analyzed in 46 patients with HLMI on angiograms; other subjects were 233 healthy controls and 194 patients with left ventricular hypertrophy. Chou's criteria had good specificity, but sensitivity was unsatisfactory (32/46, or 70%). Accordingly, we examined various parameters of the QRS and T loops and found that the addition of four new criteria to Chou's improved sensitivity (46/46, or 100%) without impairment of specificity. The additional criteria are; 1) initial counterclockwise rotation of the QRS loop, 2) the ratio of the maximal QRS magnitude to the maximal T magnitude less than 4.5, 3) direction of the maximal T between +60 degrees and +180 degrees, 4) the QRS-T angle between 40 degrees and 135 degrees, all in the frontal plane. PMID- 2601001 TI - Symposium on Protection of Ischemic Myocardium--Basic and Clinical Research. Proceedings of the 52d annual scientific session of the Japanese Circulation Society. May 13, 1988, Akita. PMID- 2601000 TI - A digoxin-like immunoreactive substance and atrioventricular block induced by a Chinese medicine "kyushin". AB - The attempted suicide by 2 women with a kyushin overdose is reported. Kyushin caused them to produce a significant elevation of a serum digoxin-like immunoreactive substance (2.35 and 1.84 ng/ml) and symptoms of nausea, vomiting and general malaise. Their blood biochemistry and electrolytes were normal. In one patient, an electrocardiogram revealed a second degree Wenckebach atrioventricular block and T-wave change. Toad venom, a kyushin ingredient, is possibly responsible for the development of these clinical features and electrocardiographic changes. PMID- 2601002 TI - Infarct size and the protection of ischemic myocardium in pig, dog and human. AB - To define whether recanalization after occlusion can reduce the myocardial infarct size, we compared the infarct size in 25 pig hearts without collateral circulation, 35 dog hearts with collateral circulation and 11 human autopsied hearts with coronary thrombolysis at 2 to 6 hours after the onset of acute myocardial infarction. The data showed that % infarct size in the risk area increased according to the duration of occlusion. In the pig, % infarct size was 80 +/- 9% in the recanalization after 1 hour occlusion and 96 +/- 2% in the recanalization after 2 hour occlusion. There was no significant difference between these and the permanent occlusion group (95 +/- 3%). In the dog, % infarct size was 35 +/- 31% in the recanalization after 4 hour occlusion and 59 +/- 27% in the permanent occlusion group. In human autopsied hearts, the infarct size was the same between the recanalization group (82 +/- 6%) and the permanent occlusion group (80 +/- 11%). The % infarct size in the recanalization groups was less than or the same as that in the hearts with permanent occlusion in dog, pig and human. Thus, it is concluded that, to reduce conclusively the infarct size, recanalization should be done within 1 hour after the occlusion in the hearts without collateral circulation and within 4 hours in the hearts with collateral circulation. So called reperfusion injury which means the greater expansion of the % infarct size than that in the permanent occlusion is not present. PMID- 2601003 TI - In vivo 31P-NMR spectroscopy at epicardium under hypoxia. PMID- 2601004 TI - Infarct sizing after reperfusion by two-dimensional echocardiography and serum cardiac myosin light chain II in conscious dogs: dissociation between early left ventricular wall motion and ultimate infarct size. AB - The time course of recovery of left ventricular wall motion after coronary reperfusion and how that relates to anatomical infarct size, wall motion abnormality, and the amount of cardiac myosin light chain II release were evaluated in conscious dogs. One week after the implantation of hydraulic occluders on the left circumflex arteries, myocardial infarction was induced. Coronary reperfusion was performed 3 h after the occlusion in 9 dogs (R) and occlusion was sustained in 9 dogs (C). All dogs underwent serial 2-dimensional echocardiograms and determination of serum cardiac myosin light chain II. The infarct size was identified at 14 days. Systolic wall thickening at the center of the ischemic area (SWT) at 3 h was -7.7 +/- 2.8% (C), -9.9 +/- 3.0% (R). Systolic thinning was observed even at 14 days in C. Significant recovery of contraction was observed in R, but the improvement continued for as long as 2 days. SWT at 14 days was -1.5 +/- 2.8% (C) and 7.0 +/- 4.6% (R) (p less than 0.05). All of SWT or the extent of systolic thinning (EST) 3-hour and 14-day were correlated well with infarct size in C. In group R, 14-day SWT and 14-day EST correlated with infarct size but 3-hour SWT and 3-hour EST did not. Total release of serum cardiac myosin light chain II levels correlated well with infarct size (r = 0.88), 14-day SWT (r = -0.90) and 14-day EST (r = 0.89) in all dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601005 TI - Effects of calcium antagonists and free radical scavengers on myocardial ischemia and reperfusion injury: evaluation by 31P-NMR spectroscopy. AB - The Langendorff perfused rat heart was used to investigate whether myocardial damage during ischemia and reperfusion could be protected by free radical scavengers, calcium antagonist and adenosine. Myocardial high energy phosphates were measured by phosphorus-31 NMR spectroscopy during normal perfusion, 20 min of ischemia and 20 min of reperfusion. In hearts, which were treated both with free radical scavengers (FRS) (Superoxide dismutase): 24 IU/ml and catalase 22 IU/ml) and verapamil (10(-7) M), beta-ATP was significantly higher than that of FRS at the end of ischemia. However, beta-ATP recovered only to 83% of baseline value at the end of reperfusion. In view of myocardial metabolism, verapamil treated hearts were good for recovery of creatine phosphate (PCr) but not ATP at the end of reperfusion. Hearts which were treated with only adenosine did not differ from control hearts. However, when hearts were treated with both verapamil and adenosine (10(-4) M), recovery of both ATP and PCr content was significantly greater than that of control hearts. These results suggested that pretreatment with both verapamil and adenosine before and after global ischemia could protect ischemic myocardium, but, further studies are necessary to clarify the precise mechanism of protection. PMID- 2601006 TI - Role of PMN elastase on ischemic myocardial injury in evolving myocardial infarction: correlation with clinical parameters and intervention by protease inhibitor ulinastatin. AB - The purposes of this study were to investigate the sequential changes of PMN elastase during evolving myocardial infarction, and also to ascertain whether or not ulinastatin (UL), a clinically useful protease inhibitor, would affect the extent of ischemic myocardial injury. The levels of plasma PMN elastase (as alpha 1-proteinase inhibitor-elastase complex) were measured once in 13 normal controls, and at intervals in 30 acute myocardial infarction (AMI) patients given UL and 30 AMI controls on conventional therapy, and compared between the groups. The levels in control group on conventional therapy were significantly higher from 6 to 72 hours after the onset than those in normal controls. Maximum PMN elastase levels in non-survivors (n = 7) were significantly higher than in survivors (n = 23) at the 6-month follow-up (288.7 +/- 75.8 vs. 188.1 +/- 56.9 micrograms/l, p less than 0.01). The maximum level of PMN elastase in patients given UL was significantly lower than that in the control group (162.2 +/- 96.2 vs 207.3 +/- 70.1 micrograms/l, p less than 0.05), and the peak CK-MB in patients given UL was significantly lower than that in controls (252.3 +/- 150.9 vs 360.1 +/- 239.6 IU/l, p less than 0.05). Early mortality (seen at 6-month follow-up) in patients administered UL was significantly lower than that of the treated controls (3.3% vs 23.3%, p less than 0.05). Analysis of changes in PMN elastase levels suggested that UL would be clinically beneficial for reduction of ischemic myocardial injury. PMID- 2601007 TI - Preliminary clinical experience with intermittent coronary sinus occlusion in combination with thrombolytic therapy in acute myocardial infarction. AB - Previous experimental studies have clarified the effectiveness of intermittent coronary sinus occlusion or ICSO. We evaluated the clinical feasibility, safety and effectiveness of ICSO in the patients with acute myocardial infarction (AMI) who were treated with concomitant thrombolytic therapy. Implementation of ICSO was obtained in 76% of the eligible patients. Twelve patients with evolving anteroseptal infarction treated with ICSO + thrombolysis were compared with 12 patients with anterior AMI treated with thrombolysis alone. Baseline characteristics were comparable between the two groups. Adverse effects of ICSO on hemodynamics, hematologic parameters and ventricular arrhythmias were not detected. Enzymatic infarct size, myocardial lactate metabolism in the acute phase, and left ventricular wall motion and Tl-201 perfusion defect at follow-up in ICSO group were slightly improved compared with controls. PMID- 2601008 TI - [The characteristics of stomach cancer diagnosed in mass screening]. PMID- 2601009 TI - [Changes in the index of atypia in large intestinal adenoma and cancer --an objective pathological diagnosis]. PMID- 2601010 TI - [Lung cancer in women--a comparison between Hong Kong and Japan]. PMID- 2601011 TI - [The degree of malignancy in lung adenocarcinoma and related factors-- nuclear DNA content and bromodeoxyuridine labeling index]. PMID- 2601012 TI - [High risk groups of breast cancer]. PMID- 2601013 TI - [Modified radical mastectomy in breast cancer]. PMID- 2601014 TI - [International comparison of prostatic cancer]. PMID- 2601015 TI - [The use of electroscope in the diagnosis of stomach cancer and the analysis of its images]. PMID- 2601016 TI - [Monoclonal antibody and purging]. PMID- 2601017 TI - [The trends in stomach cancers in Japanese]. PMID- 2601018 TI - [Autologous bone marrow transplantation--its role in the chemotherapy of solid tumor]. PMID- 2601019 TI - [The modified and radical surgery in stomach cancer]. PMID- 2601020 TI - [The epidemiology of alcoholism and liver cancer]. PMID- 2601021 TI - [Hepatitis B virus and hepatocarcinogenesis]. PMID- 2601022 TI - [Polypectomy in early large intestinal cancer and local recurrence]. PMID- 2601023 TI - [Hemoglobinopathies in Japan]. AB - One hundred and thirty one different hemoglobin (Hb) variants and 134 families with thalassemia syndrome were reported during 30 years search for hemoglobinopathy in Japan. Studies on their molecular pathology and gene abnormalities have elucidated the effects of base substitution in the genomic DNA. The expression of the abnormal gene products decreases in a graded manner as follows: hemoglobinopathies due to stable Hb variants----unstable Hb disorder--- hyperunstable Hb disorder----thalassemic expression of Hb variants----thalassemia syndrome without abnormal gene product. PMID- 2601024 TI - [Chemotherapy of adult ANLL]. AB - One hundred ninety six previously untreated patients of adult acute nonlymphocytic leukemia (ANLL) were treated with B-DOMP therapy. 102 patients were treated in the conventional rooms and 94 patients were in the laminar airflow rooms. The complete remission (CR) rates were 78.4%, and 84.0% respectively. The CR rate of the groups whose age was 60 years or older was higher for the patients treated in the laminar airflow room than those is conventional rooms (75.8% versus 60.0%), and the fatality from fungal infection was substantially lower for the laminar air-flow room patients. Non cross resistant chemotherapy based on alternate administration of Daunorubicin (DNR) and Aclarubicin (ACR) was given to 54 patients with ANLL in remission. The median duration of remission was 48.0 months, with 38.4%, patients in remission at 8 years. A plateau phase indicating freedom from the risk of leukemic recurrence is not clearly apparent yet. The most serious toxicity was drug induced cardiotoxicity from increased total dose by long term maintenance therapy. Newly planned post remission chemotherapy that incorporated Etoposide and Mitoxantrone with ACR and DNR was given to 35 patients with ANLL in remission. Seventy nine percent (79%) of patients were remaining in remission at 2 years. Because many patients experienced significant side effects after each course of therapy, intensive post remission chemotherapy should be used in a setting where the physician is always attending and ready to serve the patients. PMID- 2601025 TI - [The curative treatment of adult acute nonlymphocytic leukemia]. AB - Based on bone marrow findings and bone marrow stem cell kinetics and response to treatment, we have developed individualization of intensive induction and postremission chemotherapy for adult acute nonlymphocytic leukemia (ANLL). Thirty four consecutive adults with ANLL were treated with an intensified induction regimen and a high dose sequential postremission therapy consisting of daunomycin, Ara-C, 6-MP and prednisolone (DCMP). The first course of remission induction was continued till achievement of a complete marrow aplasia which resulted in a decrease of leukocyte count less than 0.6-0.8 X 10(9)/L, a decrease of marrow nucleated cell count to less than 8 X 10(9)/L, and a decrease of marrow leukemic cell to less than 5%. Postremission therapy consisted of 4 courses of DCMP and a course of high-dose Ara-C. The first postremission course was initiated within 2-3 weeks subsequent to the last induction course. Twenty-eight of 34 patients (82.4%) achieved complete remission. The 4 year disease free survival rate was 64.4 +/- 14.0%. The results convinced us that individualized intensive induction and postremission therapy of adult ANLL given at the time of minimal residual leukemic disease in early remission might be sufficiently effective to produce long-term DFS to be considered potential cured. PMID- 2601027 TI - [Acute childhood leukemia]. AB - The overall event-free survival of childhood acute leukemia has increased to 60 65% in ALL and to 40-60% in ANLL. This progress has resulted from a closely integrated scientific effort, including drug development, pharmacology, preclinical modeling, experimental design with respect to clinical trials, quantitative criteria for response, and a series of clinical trials in which the importance of complete remission, of dose and schedule, of sequencing chemotherapeutic agents, of pharmacological sanctuaries, and particularly of combination chemotherapy was studied. In this paper, recent treatment results of acute childhood leukemia made by the Children's Cancer and Leukemia Study Group of Japan were reviewed, and current challenges and future perspectives are discussed. PMID- 2601026 TI - [Treatment of acute lymphocytic leukemia in adult]. AB - Since April, 1978 to October, 1988, 66 acute lymphocytic leukemia (ALL) patients aged 15 to 79 (21 L1, 43 L2, 2 L3/6 Ph1+) were treated with 3 different therapeutic protocols. The drugs used for induction were VCR (VDS) + Pred, followed by DNR + VCR (VDS) + 6MP + Pred and VCR (VDS) + L-asp + Pred in protocol I, Ad + VCR + Pred in protocol II and DNR + VCR + Pred in protocol III. Complete remission (CR) was attained in 72.7% of 66 patients. The CR rate of each group as followings; 71.4% in protocol I and 75.0% in protocol II and III, respectively. The median duration of remission was 10.2 months + and the probability of being in continuous CR at 3 years was 21.9%. For the 48 patients in remission the median survival was 17.8 months and the probability of being alive at 3 years was 24.3%. The intensified induction and consolidation therapy is expected in the cure oriented treatment of adult ALL. PMID- 2601028 TI - [Comparison of conventional chemotherapy and short-term intensive chemotherapy in adult acute myeloid leukemia]. AB - We designed a short term intensive chemotherapy (DCMP-85 regimen) that completed 4 courses of postremission therapy without maintenance therapy in an effort to improve remission durations for adult patients with AML. Twenty six patients aged 14-65 yr were entered into this study. The rate of complete remission is 76.9%. A Kaplan-Meier analysis of patients entering remission predicts that 56% of patients will remain in remission at 3 years (median follow-up is 12 mo). Comparison three different conventional chemotherapies (DC(M)P, DCMP Two Step and BH-AC DMP), DCMP-85 has achieved higher CR rate and 3-year leukemia-free survival rate, so far. Therefore, we conclude short term intensive chemotherapy is getting better results. PMID- 2601029 TI - [Long-term survivors of acute leukemia in Japan]. AB - Our analysis of the 9th investigation for long-term survivors of acute leukemia (1988) is based on the answers to the questionnaire sent to about 1400 hospitals all over the country. This result makes it clear that there exist 2202 long-term survivors in Japan, now, with a recent increasing tendency; that is, 1607 children and 595 adults, and it documents also that the long-term survivors without relapse have extremely better prognosis than the relapsed long-term survivors. PMID- 2601030 TI - [Multivariate analysis of prognostic factors influencing survival in chronic myelogenous leukemia]. AB - Prognostic significance of disease features obtained at the time of initial diagnosis was analyzed in 90 patients with chronic myelogenous leukemia (CML) in chronic phase. Median survival of this population was 45.9 months. Univariate analysis revealed that splenomegaly, bone marrow basophils, bone marrow blasts, peripheral blood blasts, and bone marrow eosinophils were significant prognostic factors for survival, and that peripheral blood leukocytes counts, hemoglobin concentration, performance status, age and lymphadenopathy were factors with border line significance. There were multiple interrelationship among these disease features. Multivariate regression analysis identified that age, hemoglobin concentration, and bone marrow blasts were independent primarily significant prognostic factors for survival. The Cox model generated with three variables of age, hemoglobin concentration, and percent blasts in bone marrow provided a useful representation of risk status in the population. A hazard function derived from the patients population segregated patients into three groups with significantly different survival patterns: A lower risk group, an intermediate group and a high risk group of patients with median survival of 57.8, 49.8 and 38.4 months respectively. Survival after CML blast crisis was short and overall median survival of 54 patients with CML blast crisis was 6.4 months. A sole prognostic factor for survival in blast crisis identified by multivariate analysis was blast cell type at CML blast crisis and patients with lymphoid phenotype had a good prognosis with median survival of 9.8 months. Median survival of myeloid crisis was 4.2 months. No other disease features were identified as significant prognostic factors in the present patient population. PMID- 2601031 TI - [Hodgkin's disease]. AB - At Kanazawa University 28 patients with Hodgkin's disease were treated between 1975 and 1988. Ten patients underwent staging laparotomy by which we had to change the pathological stage in 3 patients because occult splenic lesions were detected histologically. Patients with early disease were treated mainly with radiotherapy (RT) and those with advanced disease received modified MOPP chemotherapy with or without RT. Twenty-six patients entered complete remission, and relapse occurred in 7 including 5 patients with stage III disease. Four patients died of the disease and 4 of other causes. The actuarial survival at 5 and 10 years were 80.1% and 47.1% respectively. The actuarial relapse free rate at 10 years was 65.8%. Fourteen patients are in good health after completion of treatment, and 9 healthy babies were born to 5 patients including 3 female patients. The goal of therapy in Hodgkin's disease is cure. Treatment strategy must be based on proper staging and consideration of iatrogenic morbidity such as sterility and second malignancy. PMID- 2601032 TI - [Malignant lymphoma NHL]. AB - The long-term survivors of malignant lymphoma who had been treated in Saitama Cancer Center since September 1976 were evaluated. The primary treatment was scheduled as follows; radiotherapy alone was to be delivered to the involved field only in stage I lymphoma with less than 5 cm in diameter, the remaining lymphoma was mainly treated with anthracycline-based combination chemotherapy. 25 patients were treated with primary radiotherapy, and the actuarial 5-yr relapse free survival rate was 83%. Primary adriamycin-based chemotherapy was given to 20 patients with nodal localized lymphoma. 10 patients died with this treatment and actuarial survival rate at 5 years was 41%. 36 patients with stage II lymphoma involving Waldeyer's ring were treated with primary chemotherapy. Complete response was obtained in 92% with 83% of 5-yr actuarial survival rate. 5-yr actuarial survival rate of 50 patients with advanced stage of lymphoma was 36%, but 69% of responders who obtained complete response had long-term survive. 20 patients aged 70 or older had a 31% actuarial 5-yr survival rate, however, the older patients with localized lymphoma who received primary chemotherapy had a 77% actuarial 5-yr survival rate. 10 older patients of the localized lymphoma arising from Waldeyer's ring are all surviving. PMID- 2601033 TI - [Chemotherapy of aggressive non-Hodgkin's lymphomas: a retrospective analysis of a single institution]. AB - In order to assess the curability of diffuse non-Hodgkin's lymphoma, a total of 93 patients who had entered into protocol studies in our institution was analysed retrospectively. Between 1977 and 1988, 53 large cell lymphoma (DL), 16 mixed cell lymphoma (DMx), and 24 medium-sized cell lymphoma (DM) patients with advanced disease were treated with CHOP, CHOP-Bleo, or CHOP-Bleo alternating with POEM-Bleo (5-drug combination of mitoxantrone, etoposide, vincristine, bleomycin, and prednisolone). The complete response rate was 70% for DL, 69% for DMx, and 54% for DM. The response was most durable in DL, compared with DMx and DM: the relapse-free survival rate at 5-year was 71% for DL, both 38% for DMx and DM. Almost all the relapses had occurred within 2 years in DL, DMx and DM, as well, thus responding patients over 2 years after cessation of chemotherapy appeared to have been cured. Relapse-free survival rate was almost the same for T- and B lymphoma, however, the 5-year survival rate of T-lymphoma was lower than that of B-lymphoma, reflecting the poor complete response rate of the former. Finally, the disease-free survival rate at 5-year was 39% for all the 93 patients, with a trend favoring for DL histology with a rate of 51%. The alternating CHOP Bleo/POEM-Bleo regimen appears beneficial compared with conventional regimens such as CHOP and CHOP-Bleo on the basis of response rate and response durability, and these results warrant further clinical trials. PMID- 2601034 TI - [Major prognostic factors in patients with T- and B-cell lymphomas]. AB - Major prognostic factors were analyzed by Cox proportional hazard model in 311 patients with B-lymphoma and 141 with T-lymphoma, who were treated with combination chemotherapy as the initial therapy during 1975 to 1987. Poor prognosis was associated with high grade pathology, increasing number of extranodal lesions, advanced stage, initial combination chemotherapy without doxorubicin, low total protein and intestinal lesion in B-lymphoma, but with increasing number of involved lesions, high LDH, low total protein, anemia, skin lesion and patients treated before 1982 in T-lymphoma. First three factors of each disease were the most important with risk ratio more than 2.5. New risk group was made from combination of the factors, which was ordered from low to high hazard rate. The new risk groups for T- and B-lymphoma are usefull for estimation of prognosis and determination of adequate chemotherapy of the patients. The prognostic factors of T-lymphoma were completely different from those of B-lymphoma, suggesting that T- and B-lymphoma are different disease and should be analyzed separately. PMID- 2601035 TI - [ATL (adult T-cell leukemia/lymphoma)]. AB - 128 cases of ATL (adult T-cell leukemia/lymphoma) were divided into 3 subgroups, 70 cases of acute type, 19 cases of chronic type and 39 cases of lymphoma type, and their prognosis were evaluated. Median survival time from the onset of acute type using Kaplan-Meier method was 8 months, that of lymphoma type was 14 months and that of chronic type was 50 months. Median survival time from the start of treatment of acute type was 5 months, that of lymphoma type was 11 months and that of chronic type was 22 months. Relatively short median survival time of chronic type may be due to they had some duration with observation only at first. No significant elongation of survival time could be obtained when acute type was divided into 2 stages, before and after 1982. Twelve patients with non-Hodgkins' lymphoma unresponsive to the first line combination chemotherapy were treated with combination therapy with cis-dichlorodiammineplatinum (CDDP). Ten patients were evaluable for response (4 cases of CR, 6 cases of PR). To stop the HTLV-1 carrier mothers milk for giving their children seems to be effective method to decrease the occurrence of ATL in future. PMID- 2601036 TI - [Multiple myeloma]. AB - Progress in the treatment of multiple myeloma can be considered from several points of view: (1) advent of new therapeutic agents and regimens; (2) the differentiation from variant forms; and (3) the prevention or early treatment of myeloma-associated complications. The author have discussed the following problems connected with the treatment of myeloma patients st 4 to 1988, including (1) ten-year survival in multiple myeloma; (2) complete remission in multiple myeloma; (3) complete remission in primary plasma cell leukemia; (4) systemic amyloidosis in multiple myeloma as the presenting symptom; (5) treatments for patients resistant to standard therapies; (6) treatments and courses of patients with IgD myeloma; (7) multiple myeloma in the aged; (8) treatments for patients with primary extramedullary plasmacytoma; (9) long-term observation of a patient with smoldering multiple myeloma; (10) the outcome of idiopathic Bence Jones proteinuria and (11) supportive therapies for multiple myeloma. Since the introduction of melphalan and cyclophosphamide more than two decades ago, progress in the treatment of multiple myeloma has been slow. To overstep the limits in the current chemotherapy, therapeutic strategies for individual cases should be exploited by understanding their biological properties. PMID- 2601037 TI - [Clinical response to the treatment of multiple myeloma]. AB - Between 1971 and 1985, 133 patients were diagnosed as symptomatic multiple myeloma. Recently the number and percentage of patients, who were older (70 years old) and type of diffuse proliferation, were remarkably increased. In 132 previously untreated patients who received chemotherapy, the 50% Survival time was 32 months; thirty-nine (29%) survived more than five years after treatment and 4 of them (3%) survived more than ten years. Among the prognostic factors related to survival time, serum albumin level, M-protein type, bone marrow plasma cell (%), clinical stage and classification according to tumor distribution were considered to be significantly important. Clinical responses were evaluated in 120 patients who received combination chemotherapy for at least 3 months. A 50% or more reduction of M-protein was obtained in 58% and a marked improvement in bone pain or motor-disturbance was found in 54%. Overall response rate evaluated by the effects of both objective and subjective symptoms was 43%. New criteria for response defined by the level of serum albumin and M-protein after treatment were proposed. PMID- 2601038 TI - [Duration of survival in multiple myeloma]. PMID- 2601039 TI - [Allogeneic bone marrow transplantation]. AB - The probability of long term survival for allogeneic graft patients was 63% for ALL, 64% for ANL and 40% for CML in the 1st remission or 1st chronic phase of each leukemia. The major causes of death were interstitial pneumonia, relapse of leukemia and infections. On relationship of GVHD and the long term survival, the probability of 5 years survival was 38%, 47% and 25% in grade O, I and II-IV of acute GVHD respectively. And the relationship between the relapse rate and GVHD, the patients with both of acute and chronic GVHD showed the lowest relapse rate 15.9%, the patients without GVHD showed the highest relapse rate 37.8% and the patients with either of GVHD showed the rate of between those of two groups. This may suggest that GVHD both acute and chronic might have an ability that can suppress the relapse of leukemia, i.e. GVL reaction. Interstitial pneumonia occurred in 32% of allograft patients and was often lethal complication (53%). Among many of prophylaxis tested, the followings were effective, a lower dose rate of total body irradiation, the selection of CMV-seronegative platelets donor, and the prophylactic administration of anti-CMV high titer globulin. Colony stimulating factor of human urine was also effective for shortening the granulopenic period after transplantation to prevent severe infections. PMID- 2601040 TI - [Spleen and hematopoiesis]. AB - In order to investigate the role of the human spleen on hematopoiesis, hematopoietic stem cells and stimulates were evaluated in fetal and adult spleens. BFU-E and CFU-C were existed in 20 weeks and 23 weeks fetal spleens (BFU E 145 +/- 45/10(5) mononuclear cells, CFU-C 55 +/- 6/10(5) mononuclear cells). In adult spleen, a few stem cells were recognized, which may be contaminated from peripheral blood in sinus of the spleen. We tested conditioned media from adult spleen cells for the stimulative activity on the in vitro growth of BFU-E and CFU C from bone marrow mononuclear cells. Spleen conditioned medium stimulated proliferation of these precursor cells. It seemed that PHA-stimulated spleen conditioned medium augmented BFU-E, whereas CFU-C growth was suppressed. Adult and fetal spleens were studied immunohistochemically using anti-G-CSF, GM- CSF and erythropoietin antibodies. The cells with G-CSF and GM-CSF were shown in fetal spleens. In adult spleens, however, only GM-CSF was detected. PMID- 2601041 TI - [Macrophages and erythrocytes]. AB - The mechanism by which senescent red blood cells (SRBCs) are eliminated from circulation by the reticuloendothelial system was investigated using the newly developed phagocytosis assay. Phagocytosis of SRBCs and Vibrio cholera neuraminidase (VCN) treated RBCs by autologous macrophages were significantly higher than that of unfractionated RBCs. The phagocytosis of VCN-treated RBCs was enhanced by pre-treatment of RBCs with freshly prepared autologous serum, but not with heat inactivated serum. These results suggest that the erythrophagocytosis is mediated by lectin-like receptors and complement receptors which are present on the surface of macrophages. We also studied the erythrophagocytic capacity of macrophages in the presence of tumor necrosis factor (TNF) as a model of the anemia due to acute inflammation. The phagocytosis of VCN-treated RBCs was enhanced with the addition of a small amount of TNF (1 U/ml). This result suggests that TNF enhances the destruction of damaged RBCs by activating the reticuloendothelial system. PMID- 2601042 TI - [Contribution of the spleen to the lipid metabolism in plasma and red cells. On hereditary spherocytosis and hereditary high red cell membrane phosphatidylcholine hemolytic anemia]. AB - Clinical and experimental studies on hereditary spherocytosis (HS) and high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA) were performed in relation to lipid metabolism in plasma and in red cells of these patients. In HS, red cell (RBC) membrane lipids (free cholesterol (FC) and phospholipids (PL) such as phosphatidylethanolamine, phosphatidylcholine (PC), sphingomyelin (SM) and lysophosphatidylcholine (LPC] were markedly decreased in unsplenectomized HS. Plasma lipids (total cholesterol, FC, HDL-cholesterol, PL) were also decreased in these patients. After splenectomy, substantial normalization of plasma and RBC lipids were observed. Concerning lipid kinetics, the extents of 14C-PC synthesis in RBC from 14C-LPC in medium and of 14C-PC exchange between RBC and the medium were almost identical to those in normal control in the in vitro incubation conditions. These observations indicate that the decreased RBC lipids may be induced by the shortage of lipid materials in plasma in the presence of the spleen. In unsplenectomized HPCHA, plasma lipids were also decreased same as in HS. In contrast, membrane lipids (FC and PC) were markedly increased. Even after splenectomy, increased PC contents were rather enhanced in their membranes concomitant to developing of hemolytic anemia, although plasma lipids were almost normalized. Thus RBC membrane lipids in HPCHA appeared not to be affected by plasma lipids. In experimental studies on HPCHA, 14C-PC synthesis from 14C-LPC and 14C-PC uptake in these RBC were increased, in spite that large amounts of PC were already accumulated in these RBC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601043 TI - [The aging and destruction of erythrocytes and rheology]. PMID- 2601044 TI - [Blood cell kinetics in the spleen]. AB - The mean intrasplenic blood cell transit time (STT), splenic blood cell volume (SV) and the slow mixing splenic blood cell volume (SSV) have been measured in normal subjects and patients with congestive and infiltrative splenomegaly. The normal red cell SV was 0.47 +/- 0.14 (mean +/- SD) % of the circulating red cell volume (RCV). In patients with congestive and infiltrative splenomegaly, SV was 9.82 +/- 3.55% and 0.96 +/- 0.71% of RCV, respectively. The SSV was 69.1 +/- 8.4% of the SV in normal subjects, but in patients with splenomegaly, its value was lower than that of normal SSV. The STT was 0.43 +/- 0.11 min. in normal subjects. In the patients with splenomegaly, it prolonged. But, the STT/SV and STT/SSV were rapid in patients with congestive splenomegaly and low in infiltrative splenomegaly. It seemed that SST/SV and STT/SSV were useful to distinguish between congestive and infiltrative splenomegaly. In the intrasplenic granulocyte kinetics, SV was similar to that of red cell. The STT was longer than that of red cell, in normal subjects and patients with splenomegaly. In the intrasplenic platelet kinetics, the ratio of cellular splenic volume to general circulation was the largest in platelets. The STT of platelet was the slowest in blood cells. PMID- 2601045 TI - [Polycythemia vera with an inhibitor against factor XII]. AB - A case of polycythemia vera with an inhibitor against factor XII was reported. A 60-year-old female was admitted to Hokkaido University School Hospital because of erythrocytosis and hepatosplenomegaly. The hemoglobin was 22.5 g/dl and white cell count was 9,500/microliters without immature cells. The platelet count was 484,000/microliters. Bone marrow specimens showed marked hypercellularity. Philadelphia chromosome was not found on chromosome analysis. She was diagnosed as polycythemia vera according to the criteria of polycythemia Vera Study Group. Activity of factor XII was found to be decreased on the initial examination, but she had no personal and familial history of bleeding. In order to clarify the cause of decreased activity of factor XII, her plasma was mixed with normal plasma, and then examined PTT using factor XII deficient plasma. Her plasma mixed with equivalent normal plasma did not show the correction of prolonged PTT. It was suggested that an inhibitor of her plasma was included in the IgG fraction using gel chromatography. The patient was treated with phlebotomy and administration of N4-palmitoyl (1- -D-arabinofurasyl) cytosine (derivative of cytosine arabinoside; PLAC) 200 mg/day and Busulfan (1 mg/day). Factor XII was not corrected by phlebotomy, but corrected gradually by administration of PLAC and Busulfan. PMID- 2601046 TI - [Neoplastic angioendotheliosis of B-lymphocyte origin: an autopsy report]. AB - A 56-year-old male presented with fever of unknown origin and subacute dementia which progressed to death with seizure, coma and acute deterioration of general conditions. He had splenomegaly but not skin eruption or lymph node swelling. Autopsy findings showed that mononuclear tumor cells were widespread within the lumens of small blood vessels, indicating the features of neoplastic angioendotheliosis. The involved organs were shown to be brain, lung, adrenal grand, testis, bone marrow, heart and thyroid gland. To determine the origin of tumor cells, an immunohistochemical study was carried out using a panel of monoclonal antibodies. The results indicated that the tumor cells were of B lymphocyte origin. These findings support the possibility that neoplastic angioendotheliosis is a lymphoma with proliferation in small blood vessels throughout the body. PMID- 2601047 TI - [Cerebral thrombosis in a child with acute lymphocytic leukemia during L asparaginase therapy]. AB - A 13-year-old girl with preB-ALL was admitted because of headache during maintenance therapy including L-asparaginase. Magnetic resonance imaging revealed cerebral thrombosis. Coagulation studies showed decreased levels of fibrinogen, antithrombin-III and plasminogen. The patient was treated with antithrombin-III concentrates and fresh frozen plasma and recovered quickly. These findings suggest that coagulopathy induced by L-asparaginase is associated with the pathogenesis of cerebral thrombosis. PMID- 2601048 TI - [Rapid bone marrow dissemination of gastrointestinal lymphomas after surgical resection]. AB - We describe two cases of gastrointestinal lymphoma associated with rapid bone marrow dissemination after surgical resection. Case 1: A 73-year-old male was diagnosed as having malignant lymphoma originating from ileocaecal region (diffuse medium-sized, B cell type). Tumor (8 x 8 cm) was resected but infiltrated to the peritoneum and curative operation could not be done. Two weeks after operation, elevation of LDH, pancytopenia and bone marrow infiltration of lymphoma cells developed and he died of respiratory failure. Case 2: A 69-year old female was diagnosed as having remnant gastric lymphoma (diffuse large, B cell type). Tumor size was 5 x 4 cm and swelling of the third lymph nodes was found, so curative operation could not be done. Two months after operation bone marrow infiltration of lymphoma cells was observed and she is now undergoing chemotherapy. Surgical resection is performed in the majority of patients with localized gastrointestinal lymphoma. But the operation of the advanced case must be carefully done, because the operative procedure may sometimes facilitate growth and metastasis of tumor. PMID- 2601049 TI - [Lymphoblastic lymphoma associated with subcutaneous nodules, intramuscular mass, pericardial effusion and peripheral lymphadenopathy]. AB - A 14-year-old boy was admitted to Department of Pediatrics at Mie University Hospital with a 12-day history of facial cervical edema associated with venous dilatation on the upper chest wall. On admission anterior mediastinal mass was found on chest X-ray film and computed tomography. A needle biopsy revealed non Hodgkin's lymphoma, diffuse lymphoblastic type and he was staged as III. He was treated with High-risk lymphoma protocol and achieved complete remission. At relapse he developed various manifestations unusual for lymphoblastic lymphoma including peripheral lymphadenopathy, an intramuscular mass of the lt-lower leg, multiple subcutaneous nodules at anterior chest wall and upper abdomen, and pericardial effusion. No lymphomatous infiltration into bone marrow or central nervous system was observed throughout his clinical course. Immunological phenotype of lymphoma cells from pericardial effusion was quite compatible with that of common thymocytes. However cytogenetic analysis showed unique translocation: (2; 5) (q 33; q 35). Translocations with a break at 5 q 35 have been reported in peripheral T-cell lymphoma and malignant histiocytosis. PMID- 2601050 TI - [Kaposi's sarcoma developing during corticosteroid therapy in idiopathic thrombocytopenic purpura]. AB - A case of Kaposi's sarcoma developing during corticosteroid therapy for idiopathic thrombocytopenic purpura is reported. The patient is a 58-year-old female who was admitted to Sapporo City General Hospital for bleeding tendency in March 1987. She had been treated before admission with prednisolone (over 40 mg/day) for idiopathic thrombocytopenic purpura since October 1986, but her platelet count was below 40,000/microliters. In April 1987, several dark red or blue nodules appeared on the tip of her nose, left forearm, right shoulder, trunk and tongue. These nodules rapidly grew. Biopsy specimens from the nodule of the left forearm showed the histologic changes of Kaposi's sarcoma. She was treated with irradiation. Splenectomy was done in May 1987 and prednisolone was decreased to 5 mg/day. Her platelet count was continually kept 50,000/microliters or more. Her Kaposi's sarcoma completely regressed in January 1988. The relationship of immunosuppressive therapy to Kaposi's sarcoma is discussed. PMID- 2601051 TI - [Severe aplastic anemia accompanied with abnormality of T cell subset and appearance of anti-BI antibody]. AB - A 66-year-old female was diagnosed to have severe aplastic anemia. Remission was not achieved by the ALG-oxymethorone therapy, and she was in need of RBC multitransfusion. After receiving a total of 42 units (16,800 ml) of red blood cells, it was found that her serum agglutinated strongly her own group BI cells at 4 degrees C. This agglutination disappeared in DTT solution. An eluate from her red cells also agglutinated BI panel cells, whereas Bi, O I, O i cells failed to react. It was apparent that the cold agglutinin in her serum had special affinity for I cells, which also contain B. Analysis of lymphocyte subset in peripheral blood showed T 3 (CD 3) 70.18%, T 4 (CD 4) 70.92%, T 8 (CD 8) 7.08%, T 4/T 8 = 10.1, T4 (+)2H4(+)/T4(+)2H4(-) = 1.05. Although relationship between appearance of anti-BI antibody and relative increment of CD 4 positive cells was not clear, we considered that these findings were caused by an abnormal autoimmune reaction in the patient with aplastic anemia. PMID- 2601052 TI - [Methicillin-resistant staphylococcal enterocolitis developed after induction chemotherapy in a case of acute promyelocytic leukemia]. AB - A case of methicillin-resistant staphylococcal (MRSA) enterocolitis following combination chemotherapy for acute promyelocytic leukemia is presented. MRSA enterocolitis has characteristic clinical features of high fever, frequent vomiting and watery diarrhea, and its mortality rate is very high without a proper antibiotic therapy. When the patient with hematological malignancy has the above-mentioned clinical manifestations during antineoplastic chemotherapy, appropriate antibiotics for MRSA should be promptly begun before a bacteriological diagnosis. PMID- 2601053 TI - [Various factors related to carbohydrate metabolism. Thyroid hormone]. PMID- 2601054 TI - [Various factors related to carbohydrate metabolism. Growth hormone]. PMID- 2601055 TI - [Diagnostic criteria and classification of diabetes mellitus]. PMID- 2601056 TI - [Etiology of IDDM]. PMID- 2601057 TI - [Possible pathogenesis of non-insulin dependent diabetes mellitus]. PMID- 2601058 TI - [New diagnostic tests for diabetes mellitus. Hemoglobin A1 (A1c) and fructosamine]. PMID- 2601059 TI - [New diagnostic tests for diabetes mellitus. 1,5-anhydroglucitol]. PMID- 2601061 TI - [New diagnostic tests for diabetes mellitus. N-acetyl-beta-glucosaminidase]. PMID- 2601060 TI - [New diagnostic tests for diabetes mellitus. Sorbitol]. PMID- 2601062 TI - [New diagnostic tests for diabetes mellitus. C-peptide and proinsulin]. PMID- 2601063 TI - [New diagnostic tests for diabetes mellitus. Superoxide dismutase]. PMID- 2601064 TI - [New diagnostic tests for diabetes mellitus. Transferrin in urine]. PMID- 2601065 TI - [Recent advances in the pathogenesis of diabetic neuropathy]. PMID- 2601066 TI - [Pathologic, epidemiologic and clinical studies of diabetes mellitus and arteriosclerosis]. PMID- 2601067 TI - [Non-insulin-dependent diabetes in childhood]. PMID- 2601068 TI - [Secondary diabetes]. PMID- 2601069 TI - [Continuous subcutaneous insulin infusion]. PMID- 2601070 TI - [Laboratory tests for cellular immunology: flow cytometric analysis of lymphocyte subsets]. AB - Flow cytometric analysis for lymphocyte subsets provides two kinds of data: proportion of fluorescence-positive cells (lymphocyte subsets) and the fluorescence intensity. For proportional analysis of lymphocyte subsets, lymphocytes are fractionated with a conventional gate window in scatter analysis, but if activated or enlarged lymphocytes are examined, lymphocytes should be fractionated with an extended gate window. On the other hand, fluorescence intensity of a lymphocyte subset, which represents density of cell surface antigen detected by fluorescence-conjugated specific antibody, is not measured in routine tests yet. However, data on fluorescence intensity are often more valuable than the proportions of lymphocyte subsets: e.g., decrease in fluorescence intensity, but not in proportion, of CD8+ cells in active Graves' disease, and marked decrease in fluorescence intensity of OKT4+ cells in a carrier of familial OKT 4 epitope deficiency. Furthermore, two-color flow cytometry has enabled to measure more valuable, classified subsets of lymphocytes than single color flow cytometry. For example, measurement of peripheral CD5 (Leu 1)+ B cells is very useful for diagnosis of Graves' disease and its differentiation from destruction-induced thyrotoxicosis. In conclusion, we showed that measurement of fluorescence intensity of lymphocyte subsets and two-color flow cytometry are useful for laboratory tests of lymphocyte subsets. PMID- 2601071 TI - [Clinical examination of serum bile acids for the diagnosis of hepatobiliary diseases]. AB - There are four major clinical methods for determination of serum total bile acids (TBA) levels. The first is fasting TBA (FTBA), which increases specifically in liver disorders. It increased more sensitively and normalized faster than transaminases in acute hepatic injury. Secondly, the bile acid loading test is useful to examine the degree of liver cell damage. This test improved the detection rate of FTBA for the liver dysfunction and reflects the severity of the diseases. The third is the profiles and dynamic changes of individual bile acids (IBA). In liver cirrhosis synthesis of cholic acid (CA) was lowered and the ratio of CA + deoxycholic acid (DCA)/chenodeoxycholic acid (CDCA) + lithocholic acid (LCA) was less than 1. On the other hand in cholestasis, secondary bile acids were reduced and CA increased markedly due to the regulation of bile acid metabolism, so that the ratio of CA + DCA/CDCA + LCA was more than 1. This phenomenon can be used for the differential diagnosis of liver cell damage and cholestasis. The last is the detection of unusual bile acids, such as 3 beta hydroxy-5-cholenoic acid is useful for the marker of hepatic cell carcinoma and the screening of congenital biliary atresia. PMID- 2601072 TI - [Studies on method for electrophoresis of creatine kinase (CK) MB sub-bands and its clinical application]. AB - We studied a electrophoretic method for creatine kinase (CK, EC 2.7.3.2) MB sub bands using a discontinuous buffer system on cellulose acetate membrane. The sub bands (CK-MB1 and MB2) were clearly separated using a discontinuous buffer consisting of 0.22 mol/1 tris aminomethane-glycine buffer on the anode side and 0.033 mol/l sodium barbital-boric acid buffer on the cathode side at 250 V for 30 minutes. We also examined CK-MB sub-bands in myocardial extracts that showed only a broad MB2. When the extract was incubated with normal serum havings low CK activity at 37 degrees C at MB 1 sub-band appeared within a few hours. We examined the serial changes in these sub-bands in the serum of eight patients with acute myocardial infarction (AMI). The MB2 reached a peak 7-25 hours after onset of chest pain, and MB 1 reached a peak 0-12 hours later. The ratio of MB 2 to MB 1 was high at early phase of AMI. (about 7 hours after onset of chest pain, mean 1.7 S.D. 0.78) These results indicate that a high MB 2/MB 1 ratio is a more sensitive indicator of enzyme release from necrotic myocardium, and is useful for early diagnosis of AMI. PMID- 2601073 TI - [Assay of erythropoietin in plasma by enzyme-linked immunosorbent assay]. AB - Using an enzyme linked immunosolvent assay kit supplied by Toyobo Co., erythropoietin (EPO) concentration in plasma was measured. Normal 100 samples showed a logarithmic distribution in EPO concentrations and normal range was between 5.4-32.5 mU/ml (mean +/- 2 SD). Coefficient variations (C.V.) of 3 samples continuously assayed were 3.8%, 6.5%, and 9.1% and C.V. of 3 samples assayed day by day were 3.6%, 7.2%, and 11.5%. Dilution test revealed that 3 samples diluted to 75%, 50%, and 25% were on each line which go through zero point. After the addition of 5.0, 15.0, and 35.0 mU/ml of EPO to the 3 samples, assay of EPO revealed 95.5 +/- 6.3% (mean +/- SD) of recovery. Assay of EPO in plasma from 19 patients with aplastic anemia revealed that all samples were higher than normal range and that 4 samples from the patients with severe aplastic anemia (less than 8.0 g/dl of hemoglobin) showed higher than 3,000 mU/ml. Furthermore, 67% (14/21) of samples from patients with leukemia showed higher than normal range in EPO concentration. EPO concentration in plasma from 17 patients with chronic renal failure were within normal range although the patients showed anemia. PMID- 2601075 TI - [Clinicopathological study on microscopic urinalysis as screening for malignant cells]. AB - Study on detection of malignant cells in urinary sediments using supravital staining was described. We examined 96,554 specimens of urinary sediments for 2 years from January 1985 to December 1986. The results of microscopic urinalysis were compared with the cytological and histological diagnoses. Atypical cells were found in 138 patients, and 47 (34.1%) cancers were diagnosed histologically among them. These included 33 bladder cancer, 1 ureter cancer, 1 renal pelvic cancer, 2 prostate cancers, 1 rectal cancer, and 9 uterine cancers. Seven patients of them had not been under suspicion of malignancy yet before atypical cells were detected. Therefore microscopic urinalysis caused the triggers of cancer diagnoses. For bladder cancers, the positive rates in microscopic urinalysis were 43.4%, and those in urinary cytology were 52.4%. The positivity revealed higher in high-grade cancers than in low-grade. As compared with the results between microscopic urinalysis and urinary cytology in identical patients, the rate of correspondence between them was 89.5%. In 61.2% of positive and suspicious urinary cytology, atypical cells were not found. Atypical cells were seen in negative urinary cytology of 26 cases, and 5 cases of cancers were diagnosed histologically. These suggested that microscopic urinalysis as a screening for malignant cells was useful to detect urinary tract malignancy combining with urinary cytology. PMID- 2601074 TI - [Evaluation of a modified latex agglutination inhibitory reaction method for the quantitation of urinary estriol in pregnant women]. AB - This study evaluated a modified latex agglutination inhibitory reaction method for the quantitation of urinary estriol in women during normal and abnormal pregnancy. The urinary levels of estriol in pregnant women measured by this method correlated with urinary and serum levels measured by radioimmunoassay. The urinary level of estriol rose during pregnancy and reached a peak at the time of delivery, after which it returned to the control level in a few days. In contrast, the urinary level of estriol in women with abnormal pregnancy did not rise during pregnancy. This method is useful to detect impaired function of the placenta in pregnant women. PMID- 2601076 TI - [A family of pseudocholinesterase deficiency (silent type II)]. AB - We report here a case of pseudocholinesterase (E.C. 3.1.1.8) deficiency, silent type II. The proband was a 29-year-old healthy man. His parents were cousins. A family study revealed that 9 out of 17 members of family investigated (paternal side 6, maternal side 3) concentrations. Serum cholinesterase activity were correlated well with serum albumin concentrations in both healthy people and patients with chronic liver diseases. The ratio of cholinesterase activity to albumin concentrations in serum was found more useful to detect heterozygous pseudocholinesterase deficiency than the serum cholinesterase activity alone. Both the dibucaine number and the fluoride number were within normal range in all family who showed low cholinesterase activity in serum. The amount of immunoreactive substance in serum against anticholinesterase antibody was normal in the proband as well as his family, while it was about twice of the value expected from their activity in those who had low ratio of serum cholinesterase activity to albumin concentrations. These results altogether suggested that the proband was a case of homozygous pseudocholinesterase deficiency, silent type II. PMID- 2601077 TI - [Fundamental examination and the reference values of anticardiolipin antibodies]. AB - We studied sera from 146 healthy individuals in a fundamental examination to obtain reference values for anticardiolipin antibodies by the enzyme-linked immunosorbent assay (ELISA). The good results were obtained in the evaluation of concentrations of pretreatment substances, cardiolipin antigen and serum samples, as well as in reproducibility and stability on the storage of the samples. However, there was interference by triglycerides, hemoglobin and birilubin. The O.D. values and positive values of IgG, IgA and IgM in healthy individuals were 0.105, 0.111, 0.173 and 4.1%, 2.7%, 2.7% respectively. Furthermore, the incidences of anticardiolipin antibodies in systemic lupus erythematosus, mixed connective tissue disease, progressive systemic sclerosis, Sjogren's syndrome, polymyositis/dermatomyositis, rheumatoid arthritis, unclassified connective tissue disease, polyartertis nodosa and idiopathic thrombocytopenic purpura were 48.0%, 40.0%, 50.0%, 21.4%, 26.3%, 29.4%, 40.0% and 25.0% respectively. Especially, the incidence of IgG antibody against cardiolipin was high. Detection of phospholipid cardiolipin antibodies using ELISA was considered to be a useful for clinical diagnosis and monitoring of patients with systemic lupus erythematosus and associated autoimmune disorders. PMID- 2601078 TI - [Prevention of hepatitis B--HLA DR/DQ in HBs Ag nonresponder]. AB - To evaluate the immunological background in HBs Ag nonresponders against hepatitis B vaccine, the lymphocyte surface marker and HLA-DR/DQ antigen were determined on hospital personnel, 70 males and 256 females, injected hepatitis B vaccine for three times. The vaccine made from the plasma of HBs Ag carriers was injected at the first and second vaccination and recombinant hepatitis B vaccine was injected at the third vaccination. A month after the third vaccination, blood was withdrawn for HBs antigen test by RIA. Border line cases (cut off index 1.0 1.9) are included in nonresponder (cut off index less than 0.9). Both nonresponders and low responders (cut off index 2-49) are more often seen in males than females and high responder (cut off index 50 or more) are seen more often in young females than males. Lymphocyte surface markers were studied by flow cytometry using the following monoclonal antibodies; OKT 3, 4, 8, DR, NK, Ia 1 and B7. No differences between lymphocyte surface markers of nonresponders and responders were noted. HLA-DR/DQ antigens were studied by the cytotoxicity test using Locus DR/DQ, Terasaki Second DR W-60 Tray and using following antibodies; DR 1, DR 2, DRW 15, DR 4, DR 5, DR 7, DR 9, DRW 10, DRW 8, DRW 12, DRW 13, DRW 6, DRW 52, DRW 53, DQW 1, DQW 6, DQW 2, DQW 3, DQW 7 and DQW 4. No significant differences between HLA-DR/DQ of nonresponders and responders were noted. PMID- 2601079 TI - [Preventive medicine of adult T-cell leukaemia]. AB - Preventive medicine of adult T cell leukemia (ATL) was discussed from four points of view, namely (1) seroepidemiology, (2) clinical laboratory findings of HTLV-I seropositive and seronegative groups in comparison with those of ATL patients, (3) relationship between genetic polymorphisms of 4 serum proteins and HTLV-I infection/development of ATL and (4) detection of antibodies to HTLV-I in pregnant women and prevention of its mother to child transmission. PMID- 2601080 TI - [Nosocomial infections and clinical microbiology]. AB - Hospital-acquired infection with strains of methicillin-resistant Staphylococcus aureus (MRSA) have considerably increased in recent years. In addition to being resistant to methicillin, these strains are resistant to practically all forms beta-lactams, aminoglycosides and many other antibiotics. There appears no cost effective control and preventive measures for this common but also potentially life-threatening disease. Although not clearly presented, the overall cost for the treatment of patients infected with MRSA should be enormous. Can laboratory medicine (or clinical microbiology) contribute to this global medical problem? Multiple strains of MRSA circulate within a hospital and some strains are even localized within specific wards. These facts suggest yet undisclosed routes of transmission and/or foci of infection. Triumph over these versatile organisms may have to await the development of new antibiotics effective for MRSA. PMID- 2601081 TI - [Campylobacter pylori and diseases of the stomach]. AB - In spite of extensive clinical studies the pathogenicity of Campylobacter pylori in various diseases of the stomach is still not fully elucidated. In peptic ulcer Campylobacter pylori has not provided a reasonable explanation for the localized and solitary development of ulcer lesion which is one of characteristic features of this clinical entity. Our previous clinical study revealed that relapse occurs mostly at or near the scar of the preceding ulcer lesion and occurs more often in red scar than in white scar in peptic ulcer. Therefore, the scar was chosen to investigate whether there is a correlation between Campylobacter pylori and relapse. Twenty patients with healed gastric ulcer were biopsied in duplicate at 4 different sites, namely at the center of and near the scar of the preceding ulcer lesion, in the body and pyloric antrum. One of the duplicate specimen was stained, and the other cultured. Number of the colony observed on the plate was highest at the scar center followed by near the scar or in the body, and the pyloric antrum showed the lowest. Campylobacter pylori was detected in 46.7% of red scar, and 20% of white scar. Campylobacter pylori may play a pathogenic role in some patients of peptic ulcer, but not in all. Namely Campylobacter pylori is one of factors which may cause in imbalance between offensive and defensive powers at gastric mucosa and may lead to development of ulcer lesion. In case of positive bacteriological test, therefore, as to presence of Campylobacter pylori, the preventive measure for relapse such as bismuth preparation may be considered. PMID- 2601082 TI - [Morphological studies on eosinophils in leukemia]. AB - We investigated morphological changes on eosinophils in two cases each of M2, M4, MDS, and two other cases which showed eosinophilia of more than 5% in bone marrow. Several abnormalities were observed in eosinophils in cases of leukemia. The findings under light microscope frequently revealed granular abnormalities in acute leukemia and nuclear abnormalities in MDS. In acute leukemia, eosinophils were barely detectable in the peripheral blood cells and immature eosinophils increased in the bone marrow. Some cases of acute leukemia showed crystalloid abnormalities in morphology and an increase of eosinophils lacking crystalloid. There was a tendency toward larger-sized granules in cases of M2 and smaller sized granules in cases of M4. We think that these eosinophils tumorous. It is necessary to accumulate date on more cases, but it seems that, to some extent, there are uniform abnormalities associated with each of the different forms of leukemia. PMID- 2601083 TI - [Clinical evaluation of serum TAC-41 in various digestive cancers]. AB - Tumor associated carbohydrate antigen TAC-41 identified by the monoclonal antibody against a gastric adenocarcinoma cell line. We evaluated the serum levels of TAC-41 in 55 patients with various malignancies and 44 patients with benign diseases, and compared them with the serum levels of other tumor markers including CA 19-9 and CA-50. When the normal range of serum TAC-41 level was less than 40 dilution titer, the positive rate for malignancies of TAC-41 was 100% in pancreas cancer, 80% in biliary tract cancer and 87% in hepatocellular carcinoma. On the other hand, specificity (64%) of TAC-41 in all patients was less than that of other tumor markers. However, efficiency (68%) of TAC-41 was no less than those of other tumor markers. Comparison of the serum levels of TAC-41 with CA 19 9 or CA-50 in the same samples revealed a highly positive correlation (r = 0.891) in patients with various cancers. These results indicate that TAC-41 is clinically no less useful than CA 19-9 or CA-50 as a tumor marker. The usefulness of this method is characterized by its short turnaround time and lower cost than other tumor markers. Eventually, TAC-41 is one of the most useful tumor marker in mass screening for digestive malignant diseases. PMID- 2601084 TI - [Analysis of the result of thyroid microsomal particle agglutination test by ELISA]. AB - No accurate method to detect thyroid microsomal (MC) antibody (Ab) in serum has been generalized. In this study, the titer of MC Ab obtained by the method of MC autoantibody particle agglutination (MCPA) was analyzed by enzyme linked immunosorbent assay (ELISA). MC and thyroglobulin (Tg) were prepared from Graves' thyroid. ELISA was done by coating the plate with MC, adding Tg to buffer and using peroxidase-conjugated anti-h IgG. 1) The titer of MCPA correlated with the MC Ab ELISA index in serum without Tg Ab, but it did not in serum with Tg Ab. MC Ab was negative by ELISA while it was positive by MCPA in some of the sera with Tg Ab. 2) When ELISA was done using buffer without Tg, the amount of IgG bound to MC was greater in serum with TGPA: + and MCPA: - than in serum with MCPA: + and TGPA: -. 3) The zone phenomenon observed in MCPA did not always indicate an excess of MC Ab. 4) MC Ab was positive by ELISA in some of the negative MCPA sera obtained from patients with Hashimoto's disease in which diagnosis was confirmed by biopsy. In conclusion, the result obtained in MCPA now in use is strongly influenced by Tg Ab. Furthermore, since binding of Ab to MC is judged by agglutination of particles in MCPA, ELISA is superior in sensitivity and accuracy in detecting MC Ab. PMID- 2601085 TI - [Changes in serum parathyroid hormone levels during pregnancy]. AB - As pregnancy poses a significant challenge to maternal calcium homeostasis, it is interesting to investigate a change in serum parathyroid hormone (PTH) level throughout pregnancy. PTH metabolism in pregnancy has not been clearly defined. We have made an attempt to evaluate changes in serum intact PTH level during pregnancy. Compared with nonpregnant women, serum intact PTH concentrations were decreased significantly in pregnant women during the first and the second trimester, but not during the third trimester. Nephrogenous cyclic AMP excretion, index of parathyroid function has been reported to be decreased in pregnant women during the first and second trimester, but to be in normal range in pregnant women during third trimester. Our finding consisted with these facts. PMID- 2601086 TI - [Rapid diagnosis of gram-negative bacteriuria with endotoxin-specific chromogenic test]. AB - Limulus amebocyte lysate test is a simple, yet sensitive laboratory method for detecting endotoxin. Although the specificity of the test was questioned, we recently solved this problem by removing a (1----3)-beta-D-glucan-sensitive factor G from the lysate (Endospecy, Seikagaku Kogyo Co., Ltd, Tokyo). In this study, we have established a method for the determination of endotoxin urine in using Endospecy. An aliquot of 0.2 ml of Endospecy dissolved in 4.4 ml of 0.1 mol/l Tris-HCl buffer (pH 8.0) was added to 5 microliter of urine sample. The mixture was incubated at 37 degrees C for 30 min. After diazo-coupling, absorbance was measured at 545 nm. The standard curve using Escherichia coli 0111: B4 endotoxin showed a good linearity. The addition-recovery test of various endotoxins showed nearly 100% recovery. Normal urine contained less than 60 pg/ml of endotoxin. Urine from patients with Gram-negative bacteriuria showed definitely high values, whereas urines infected either with Gram-positive bacteria or with fungi all showed nearly normal values. This method will be useful as a rapid and reliable test for the diagnosis of urinary tract infection with Gram-negative bacteria. PMID- 2601087 TI - [Clinical evaluation of surveillance culture in cancer patients]. AB - To clarify usefulness of surveillance culture (SC) as a predictor of infection, we retrospectively studied 70 episodes of bacteremia in 271 cancer patients between April, 1984 and April, 1988. SC was obtained from the throat swabs, stool and urine on admission and then once weekly during hospitalization. Of 76 aerobic strains from blood, 18 (24%) were isolated from SC prior to bacteremia. Seven strains were first identified from SC within 4 days before bacteremia occurred. Of 63 cases of bacteremia, excluding polymicrobial bacteremia, 14 (22%) were initially detected by SC. An antibiotic therapy was altered within 5 days after bacteremia in 19 bacteremic patients with negative SC and 5 with positive SC. Six bacteremic patients with negative SC and 3 with positive SC died within 5 days after the onset of bacteremia. No significant differences were observed in antibiotic therapy (chi 2 test, p less than 0.05) or mortality (p greater than 0.05) between patients who had positive and negative SC. Routine SC is unlikely to influence an initial diagnosis or antimicrobial management for cancer patients with fever. PMID- 2601088 TI - [X-ray computed tomography of the pancreas]. PMID- 2601089 TI - [Magnetic resonance imaging of the pancreas]. PMID- 2601090 TI - [X-ray computed tomography and magnetic resonance imaging of the urinary bladder]. PMID- 2601091 TI - [X-ray computed tomography and magnetic resonance imaging of the ovary and the peritoneal cavity]. PMID- 2601092 TI - [Recent progress of neuro-imaging for the diagnosis of dementia]. PMID- 2601093 TI - [Cerebrovascular dementia; correlation of computed and histopathologic findings]. AB - Computed tomography is often insensitive to such lesions as atrophic demyelination, enlarged perivascular spaces and infarction in the periventricular white matter. In attempt to better understand the discrepancy between the pathologic and X-CT findings, the author correlated areas that had focal, patchy on X-CT and brains with gross and microscopic findings. Patients with cerebral strokes had larger volume infarcts characterized centrally by necrosis, axonal loss, and demyelination. The progressive subcortical vascular encephalopathy (Binswanger's disease) is characterized by ischemic demyelinization of white matter provoked by hypertensive vascular changes in small vessels and is usually accompanied by multiple lacunar infarcts in a periventricular area and the basal ganglia. Small, deep hemispheric infarcts may be of no clinical significance unless a sufficient aggregate of these occurs. It should be pointed out that many small infarcts are clinically silent, and chronic multifocal ischemia may be responsible for observed senescent changes in cerebral tissue. The extension of the infarcted area might be most important in the development of cerebrovascular dementia. Mixed forms of degenerative dementia and any type of cerebral vascular disease are common and account for 10-20% of all dementias. PMID- 2601094 TI - [Clinical application of brain perfusion SPECT imaging to dementia]. AB - Brain perfusion SPECT imaging has been applied to patients with dementia using 123I-IMP and 99mTc-HM-PAO. Brain blood flow closely parallels regional brain metabolism or brain function with normal cerebrovascular function. Therefore neuronal activity can be indirectly evaluated by in vivo brain perfusion imaging in dementia. This nuclear medicine technique is quite useful for the differential diagnosis, assessment of the degree and localization of the affected area, disease course, and therapeutic effect. IMP seems to be superior to HM-PAO in detecting focal decreased perfusion and quantitative analysis. Hereafter the brain perfusion SPECT study will be more widespread. Neuroreceptor imaging is highly expected as the next step of a brain SPECT study. PMID- 2601095 TI - [F-18 FDG PET in dementia]. AB - Glucose metabolism was measured by F-18 FDG PET in 33 patients with dementia. In patients with DAT, rCMRgl showed marked decrease in the associated areas in the temporo-parietal lobes, and it was relatively preserved in the primary cortices such as sensory, motor and visual areas. Frontal lobes were also involved in patients with advanced disease. In Pick disease, the frontal lobes were severely impaired. Multi-infarct dementia, Parkinson dementia and supranuclear palsy showed diffuse or multiple involvement throughout the entire brain. Correlation with rCMRgl and clinical severity was found in DAT patients. In conclusion, F-18 FDG PET is clinically useful in the differential diagnosis and grading of dementias. PMID- 2601096 TI - [Cerebral glucose metabolism in dementia (PET-FDG study)]. AB - Positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) was employed to assess regional cerebral glucose metabolism which is tightly coupled to neuronal activity in the brain. In Alzheimer's and multi-infarct dementia, hypometabolism of glucose was found in frontal, temporal, and parietal association cortices. Focal hypometabolism in association cortices was observed in depression, epilepsy, ALS and other neurological diseases without any symptoms of mental deterioration. These results might indicate that not focal but global decrease of neuronal activity in the association cortex induces demented state. PMID- 2601097 TI - [Pathophysiology of dementia and medical imaging]. AB - Dementia is not a particular disease but a clinical syndrome based on the subjective and objective symptoms. Morphological imaging modalities such as X-ray computed tomography (CT) and magnetic resonance imaging (MRI) can accurately identify those which can be treated. Functional imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can visualize the regional decrease of neuronal function as mapping of cerebral blood flow and metabolism. Although they are useful for differential diagnosis and assessment of neuronal activity in patients with dementia, they cannot provide an information about the dementia itself. Recent rapid developments in molecular biology have started to clarify the underlying pathophysiology of various neurological diseases. A combination of these knowledge and the new imaging technique may bring an exciting new field in understanding the cause and the treatment of dementia. PMID- 2601098 TI - [Recent progress of neuro-imaging for the diagnosis of cerebrovascular disease and dementia]. PMID- 2601099 TI - [The current treatment of maxillary carcinoma]. AB - Several characteristics of maxillary sinus and oral maxillary squamous cell carcinoma have been discussed, After trimodal combination therapy have been introduced to both cancers, improved local control have been obtained. In addition to elevation of survival rate, neck metastases and double cancers have become the problems to be solved. PMID- 2601100 TI - [MR imaging of the inner ear; findings of Meniere's syndrome]. AB - Symptoms in Meniere's disease are explained by hydrops of endolymphatic system with recurrent ruptures of the membranous labyrinth. The primary cause of the increased endolymphatic volume appears to be an imbalance between secretion and resorption of endolymph which may be due to an obstruction of the endolymphatic duct and sac, located in the vestibular aqueduct. Non-visualization or narrowing of the vestibular aqueduct of the paper have been demonstrated by conventional tomography and high resolution computed tomography (HR-CT). But the endolymphatic duct and sac can not be obtained by HR-CT and conventional tomography. Whereas, on MRI, these are identified. By MRI, we prospectively tried to demonstrate morphological alterations in 10 patients with Meniere's disease and in 4 patients with vestibular neuronitis. These were compared with a group of 20 normal men. Visualization of the endolymphatic duct and sac (vestibular aqueduct) on MRI was assessed. There was a distinctly decreased visualization of the vestibular aqueduct in the Meniere group and vestibular neuronitis group. We were able to confirm a statistically proven usefulness of the MRI technique in identifying an anatomical abnormality which is directly in correlation with the side of the lesion in cases of unilateral Meniere's disease. PMID- 2601101 TI - [MR findings of metastatic brain tumors]. AB - Fifteen cases with metastatic brain tumor(s) were examined on a 1.5T MR system and the results were evaluated along with images of contrast-enhanced CT. Gd-DTPA enhanced T1-weighted imaging (T1WI) showed the best detectability of lesions and was followed by contrast-enhanced CT, T2WI, and non-enhanced T1WI in that order. No correlation was found between the MR signal intensity and the histological classification of the tumors. In differential diagnosis with glioblastoma, several signal characteristics were encountered. Low or isointensity as well as the discrimination of tumor from edema on T2WI was considered to suggest the diagnosis of metastatic tumor. PMID- 2601102 TI - [Subdural hematoma from ruptured arteriovenous malformation; demonstration by MR imaging]. AB - We studied MRI of 15 cases of arteriovenous malformation (AVM) with special reference on the coexistence of the subdural hematoma. All ruptured cases (6 cases) were associated with intracerebral hematoma, and half (3 cases) of them were coexisted with subdural hematoma. In one of them, the presence of the subdural hematoma promoted us to perform angiography which revealed the AVM. PMID- 2601103 TI - [MR measurement of normal brainstem cerebellum and corpus callosum on midsagittal section]. AB - The dimensions of the brainstem, cerebellum and corpus callosum were measured on magnetic resonance (MR) images with sagittal spin-echo sequence. Eighty-two normal adults (average 49.6 years old) were measured. The mesencephalic, pontine or cerebellar diameters and lengths could be measured more accurately and reproducibly than medullary diameter and length. The anterio-posterior diameter of the pons and the cerebellum was 23.2 +/- 1.4 mm and 26.4 +/- 2.5 mm respectively. The length of the pons and the cerebellum was 27.8 +/- 2 mm and 45.8 +/- 3.5 mm respectively. We have observed focal thinning at the body of corpus callosum in 73%. This narrowing is almost unquestionably a normal variant. PMID- 2601104 TI - [MRI of the paranasal sinus mucopyocele]. AB - Seven cases of the paranasal sinus mucopyocele were examined by MRI. All of the mucopyocele in our series were clearly demonstrated on MRI using long SE pulse sequence as high signal intensity. However, the degree of signal intensity was varied based on the contents of the mucopyocele. We can detect the mucopyocele as a three dimensional image by MRI, however, CT was necessary for evaluating the bone destruction caused by mucopyocele. PMID- 2601105 TI - [Evaluation of CT myelography and conventional myelography for avulsion injury of nerve root--18 cases of birth palsy]. AB - CT myelography (CTM) and conventional myelography were reviewed in 18 cases of birth palsy with clinically suspected avulsion injury. A traumatic meningocele was detected in 45 roots by CTM, and in 35 roots by myelography. CTM misinterpreted only one root with a very small meningocele. CTM was superior to myelography in delineating a traumatic meningocele, because CTM is sensitive to a poorly enhanced meningocele. On the other hand, CTM missed 9 avulsed roots without a meningocele. By myelography, these 9 roots were diagnosed as 6 roots of complete avulsion injury and 3 roots of incomplete avulsion. Myelography is indispensable in evaluating nerve root avulsion. PMID- 2601106 TI - [Bone scintigraphy of the McCune-Albright syndrome]. PMID- 2601107 TI - [Treatment of rectal neoplasms]. PMID- 2601108 TI - [MR imaging of the brain in Wilson's disease]. AB - Two cases of Wilson's disease, who had been treated for eight years, were examined by MRI at 1.5 tesla. MRI of both cases demonstrated lesions with prolonged T1, prolonged T2 and partially shortened T2 in bilateral lentiform nuclei. Lesions with prolonged T1 & T2 may reflect small cavitary lesions. On the other hand, shortened T2 area may be caused by copper deposits. PMID- 2601109 TI - [A study on the estimation of prevalence of epidermolysis bullosa in Japan]. AB - An estimation of the prevalence of epidermolysis bullosa was carried out in Japan. A questionnaire was sent by mail to the departments of dermatology and pediatrics in 644 main hospitals throughout Japan requesting confirmation of the number of epidermolysis bullosa cases experienced. The response rate was 63.0% or 406 hospitals. Based on the secondary questionnaire survey, we confirmed 393 cases of epidermolysis bullosa, and then divided them into the five following groups: "simplex" type 182 (48.2%), "junctional" type 23 (6.0%), "dominant dystrophic" type 72 (18.7%), "recessive dystrophic" type 109 (28.2%), unclassified 7 (1.8%). Using the respondent rate by geographic region and clinical department, the estimated prevalence of each type of epidermolysis bullosa was calculated as follows: "simplex" type 340-470 (0.29-0.40 per 100,000 population), "junctional" type 18-24 (0.015-0.020), "dominant dystrophic" type 130-180 (0.11-0.15) and "recessive dystrophic" type 180-250 (0.15-0.21). The total number of epidermolysis bullosa patients in Japan was estimated as being more than 670 in 1983. PMID- 2601110 TI - [Microcystic adnexal carcinoma--a light and electron microscopic studies]. AB - Microcystic adnexal carcinoma (MAC) in a 48-year-old Japanese male was studied. A firm nodule had appeared on the right side of his upper lip at the age of 38 years and then had gradually enlarged. Light microscopic examinations revealed numerous strands and islands of basaloid cells and keratinous cysts with desmoplastic stroma in the dermis and subcutaneous tissue. Some keratinous cysts showed early calcification and some contained pilar structures. Clear cells resembling sebaceous gland cells were observed in the strands of tumor cells connecting the keratinous cysts. In the middle dermis, there were small ductal structures containing amorphous eosinophilic material. Immunoperoxidase staining for carcinoembryonic antigen was focally positive in the lumina of small ducts, on the ductal lining surface of tumor cells, and in the contents of keratinous cysts. Electron microscopic examinations revealed tumor cells resembling non keratotic keratinocytes, and containing tonofilaments, mitochondria, and vacuoles. In some parts, tumors were differentiated to various types of sebaceous gland, sweat duct, or sweat secretary segments. Sebaceous gland cells contained lipid droplets and glycogen. Tumors differentiated to sweat duct had a marked similarity to embryo eccrine duct in the lower epidermis because of the presence of multivesicular dense bodies and periluminal filamentous zones and the absence of myoepithelial cells. Tumors differentiated to sweat secretary segments had a similarity to embryo eccrine secretary segments because of the absence of multivesicular dense bodies, periluminal filamentous zones and myoepithelial cells. PMID- 2601111 TI - [Three cases of dry cleaning dermatitis]. AB - Acute irritant dermatitis caused by contact with dry cleaned clothes (slacks, jacket, and skirt) was observed in three young females. Irritant sensations were noticed within an hour after wearing the clothes in all cases, but two patients thought that stocking were the cause. All patients continued wearing the clothes for various reasons. When they took off the clothes 3 to 9 hours later, erythema, edema, and bullae were noted on the posterior aspect of the thighs, the inner side of the right upper arm or the belt portion of the waist. Dry cleaning solvents used were not perchloroethylene, but were so-called new petrolatum solvents in all three cases. They were composed of paraffins in one case and paraffins plus naphtens in the other two cases. All solvents contained practically no aromatic substances. No spontaneous flare up was noted in any case. Therefore, dry cleaning solvents remaining in the clothes were thought to be the causative agent of this acute irritant contact dermatitis. This seems to be the first published report of dry cleaning dermatitis in Japan. PMID- 2601112 TI - [Physiological analysis of the facial skin by corneocyte morphology and stratum corneum turnover]. AB - In order to clarify the properties of facial skin, we measured corneocyte size and stratum corneum turnover rate on the face of healthy female volunteers in relation to age and compared the data with those from the flexor surface of the forearm. The corneocyte size on the face was found to be significantly smaller and the percentage of nucleated corneocytes was distinctly higher than those on the forearm. Stratum corneum turnover rate on the face was also approximately two times faster than on the forearm. The corneocyte size increased with aging on the forearm, but not on the face. Additionally, turnover rate decreased with aging on the forearm, but not on the face. These findings suggest that the facial skin is apparently influenced by some exogenous or endogenous factors which seem to overcome the influence of intrinsic aging effects. PMID- 2601113 TI - Antitumor activity of an extract of Cordyceps sinensis (Berk.) Sacc. against murine tumor cell lines. AB - A warm water-extract (ECS) prepared from dried Cordyceps sinensis (Berk.) Sacc., a Chinese traditional medicine, was tested for antitumor activity in vivo and in vitro. Ehrlich ascites carcinoma cells (EAC), allogeneic to ICR mice and Meth A fibrosarcoma (Meth A), syngeneic to BALB/c mice were used as the target tumor cell lines. Mice were inoculated i.p. with 1 x 10(6) EAC or 1 x 10(5) Meth A on Day 0, and ECS or saline (control) was injected i.p. to the mice from Day 1 to Day 4. ECS-treatment increased the median survival time of the allogeneic mice inoculated with EAC to 316% of the control. Eight of the 10 ECS-treated mice survived on the 60th day (Day 60) after EAC implantation. ECS-treatment also increased the median survival time of the syngeneic mice inoculated with Meth A to 312% of the control. Half of the ECS-treated mice survived on Day 60. On the other hand, no cytotoxic effect of ECS was found on either EAC or Meth A in vitro. The antitumor effect of ECS seen in the allogeneic mice was significantly reduced when the mice received whole body X-irradiation (5 Gy) before EAC implantation. These results suggest that the antitumor effect of ECS may be mediated through its immunomodulating action. PMID- 2601114 TI - The effects of ciclosporin on the renal histopathological aspects in (NZB x NZW)F1 mice. AB - Ciclosporin A (CYA) is a newly developed immunosuppressant and has a sparing effect on suppressor cell regulatory mechanism. However, accumulation of experimental animal studies has not been enough for the administration of CYA to human autoimmune diseases such as lupus nephritis. In this study, the histopathological aspects of the kidney in (NZB x NZW)F1 mice after administration of CYA were analysed. A dose of 25 mg/kg/day of CYA was injected intraperitoneally so that serum level of CYA was controlled from 250 to 300 ng/ml with this dosage. Typical histopathological changes of lupus nephritis including wire-loop lesions were observed in the kidney of the non-treated control group. In contrast, only few lesions were demonstrated in the CYA-treated group. These results suggest that CYA prevented the renal deterioration in lupus mice. PMID- 2601115 TI - [Effect of palmitate and phorbol ester on synthesis of phosphatidylcholine in isolated guinea pig gastric glands]. AB - To better understand the mechanism of phosphatidylcholine synthesis in the stomach, [3H] choline incorporation into phosphatidylcholine in response to agents which have been shown to induce phosphatidylcholine biosynthesis in other tissues was examined using isolated guinea pig gastric glands. Palmitate and 12-O tetradecanoyl phorbol 13-acetate (TPA) which has been shown to activate protein kinase C directly, stimulated [3H] choline incorporation into phosphatidylcholine in gastric glands, by 189 +/- 12.9%, and 129 +/- 10.4% of control, respectively (n = 4, p less than 0.01, p less than 0.05). On the other hand, dibutyryl cyclic AMP had no effect on the incorporation. When the glands were pulsed with [3H] choline followed by incubation in the presence of palmitate and TPA for 180 min to see the effects of the agents on the limiting step of the phosphatidylcholine synthesis, phosphatidyl-[3H] choline was increased to 167 +/- 7.5% and 142 +/- 7.5% of control respectively (n = 4, p less than 0.01, p less than 0.05). In parallel to the increase in phosphatidylcholine synthesis, phosphoryl-[3H] choline in the glands incubated with palmitate and TPA was decreased as compared with control. These results suggest that palmitate or TPA may stimulate phosphatidylcholine biosynthesis through the activation of cytidylyltransferase in the stomach. PMID- 2601116 TI - [Development and clinical application of ICG clearance meter]. AB - We have developed a finger-piece method that can indicates an accurate concentration of ICG based on the two wavelength spectrophotometry. Seventy-eight subjects were evaluated by this new method. The ICG clearance curve obtained from ICG clearance meter showed a rapid increase 20 or 40 seconds after the bolus injection. The curve decreased gradually, and increased again at 60 or 70 seconds. Plasma disappearance rate (PDR) by this method (XK ICG) was calculated by the at least square method from 600 data obtained from 5 to 15 minutes after the injection. There was a significant correlation between conventional PDR (KICG) and new method (XK ICG) also. We assume that this method have a possibility to discover new aspect of pharmacokinetics of ICG. PMID- 2601117 TI - [Morphological changes of the hamster gallbladder in the contracted and distended states]. AB - The hamster gallbladders were investigated to clarify the morphological changes in the contracted and distended states. 1) The mucosal surface showed the highly convoluted folds in the contracted state, and the flat structure in distended state. 2) The height and width of mucosal epithelial cells were changed in correspondence with the contracted and distended state of the gallbladder. 3) A subepithelial blood capillary formed a well developed network, and possessed many pores opening mainly toward the mucosal epithelial cell. Three-dimensional structure of blood capillary was closely related to the morphological changes of the mucosal fold. 4) A contraction of distention of muscle layer of the gallbladder produced concomitant widening or narrowing of the lymphatic vessel lumen. It is suggested that muscular contraction worked as a "pump" for the lymphatic flow. 5) Smooth muscle cells in the muscle layer had many cell-to-cell junctions, but few neuromuscular junctions. It seems that there is a complicated interaction between nervous and humoral control mechanisms. PMID- 2601118 TI - [Purification of human pancreatic kallikrein and organ-specificities of human glandular kallikreins]. AB - Human pancreatic kallikrein (H. Panc. K.) was purified from human pancreas by serial liquid chromatographies. The final preparation had a specific activity of 9.2 AU/A280 (AU: amidase unit for H-Pro-Phe-Arg-MCA) and its N-terminal sequence coincided with the reported sequence determined from cloned cDNA analysis. In HPLC (gel filtration), one symmetrical peak corresponding to a molecular weight of 48,000 was obtained. In SDS-PAGE without 2-mercaptoethanol, one band corresponding to a molecular weight of 52,000 was obtained. Protease inhibitor specificities of H. Panc. K. were the same as those of human urinary kallikrein (HUK) and hog pancreatic kallikrein (hog Panc. K.), while anti-HUK rabbit antibody inhibited the activities of H. Panc. K. and HUK, but not that of hog Panc. K. From the analysis of affinity for concanavalin A and erythroagglutinating phytohemagglutinin, the carbohydrate parts of H. Panc. K. are relatively rich in bi-(or multi-) antennary complex type sugar chains with bisecting GlcNAc compared with those of human salivary kallikrein and HUK. These findings will be a help to clarify the physiological and pathophysiological roles of H. Panc. K. in the pancreas and pancreatic diseases, especially in acute pancreatitis. PMID- 2601119 TI - [Basal plasma cholecystokinin levels in digestive diseases--comparison between CCK-8 like bioactivity by bioassay and CCK immunoreactivity by radioimmunoassay]. AB - Basal plasma cholecystokinin levels were measured by a bioassay using dispersed rat pancreatic acini in various digestive diseases and compared with corresponding values by CCK-8 specific radioimmunoassay. The mean basal level in healthy volunteers was 0.40 +/- 0.06 pM. The basal level in liver cirrhosis was significantly elevated to 0.92 +/- 0.14 pM. The patients with cholestasis, that is, primary biliary cirrhosis and obstructive jaundice due to choledocholithiasis, bile duct cancer or lymph node metastasis , had markedly increased basal plasma CCK-8 like bioactivities from 1.88 pM to more than 25 pM. These CCK bioactivities were not correlative with CCK immunoreactivities. It was concluded not only that basal plasma CCK in patients with bile flow disturbance were truly increased, but also that interfering substances of the bioassay might appear in the plasma of these patients. PMID- 2601120 TI - [A case report of Crohn's disease complicated with renal amyloidosis]. PMID- 2601121 TI - [A case of viral hepatitis type A associated with aseptic meningitis]. PMID- 2601122 TI - [Pharmacokinetics of thyroid hormones in a patient with hyperthyroidism associated with subacute hepatitis]. PMID- 2601123 TI - [A non-parasitic huge hepatic cyst with obstructive jaundice treated with absolute ethanol]. PMID- 2601124 TI - [Efficacy of antithrombin-III in a case of portal thrombus]. PMID- 2601125 TI - [On attachment]. PMID- 2601127 TI - [Father-child attachment]. PMID- 2601126 TI - [Mother-child relationship in clinical psychology]. PMID- 2601128 TI - [Assistance in attachment formation: a case study]. PMID- 2601129 TI - [Care desired during formation of mother-child attachment]. PMID- 2601130 TI - [Attachment formation: nurturing the maternal attitude]. PMID- 2601131 TI - [Midwives in the United States]. PMID- 2601133 TI - [A visit to the Royal Women's Hospital (Australia)]. PMID- 2601132 TI - [Study on the attitude of nursing students to sex and maternity]. PMID- 2601134 TI - [Diagnosis of newborn infants. 2. Normal and abnormal findings observed frequently in newborn infants]. PMID- 2601135 TI - [Psychology of "Kiko", an ancient exercise method. 2]. PMID- 2601136 TI - [Lutein cyst]. PMID- 2601138 TI - [Problems in nursing management at facilities specializing in obstetrics]. PMID- 2601137 TI - [Management of obstetrical care in a general hospital. View of a nursing director]. PMID- 2601139 TI - [Management of obstetrical nursing at a combined ward for obstetrics and gynecology]. PMID- 2601140 TI - [Experience in management of a newly established mixed ward of pediatrics and gyneco-obstetrics]. PMID- 2601141 TI - [Cooperation between obstetrics and pediatrics: for better nursing for the patient]. PMID- 2601142 TI - [Nursing management of an ambulatory clinic for gyneco-obstetrics: for improved cooperation with other departments]. PMID- 2601144 TI - [Interview with Dr. Itsuro Yamanaka, Director, Okayama National Hospital, who has dedicated his life to the care of newborn infants]. PMID- 2601143 TI - [Care of a patient with premature rupture of fetal membrane using Promfense (a silicon balloon which is transcervically inserted to protect the fetus)]. PMID- 2601145 TI - [Results of the effort to encourage breast feeding by adapting the SMC breast care method]. PMID- 2601146 TI - [Introduction of a revised nursing curriculum]. PMID- 2601147 TI - [Opening a "Teens' library" for providing sex related information and counseling of teenagers]. PMID- 2601148 TI - [Diagnosis in newborn infants. 3. Major abnormalities and diagnostic approaches]. PMID- 2601150 TI - [Working as a member of the medical service in a developing country]. PMID- 2601149 TI - [IUGR and the placenta]. PMID- 2601151 TI - [Psychology of "Kiko", an ancient exercise method. 3. Animal power]. PMID- 2601152 TI - [Cutting edge of cancer research and treatment]. PMID- 2601153 TI - [Basis of treatment and care of cancer patients]. PMID- 2601154 TI - [Current trends in screening of uterine cancer]. PMID- 2601155 TI - [Nursing of an expectant patient suffering from cervical cancer: on life and death from the midwifery viewpoint]. PMID- 2601156 TI - [Response to apprehension of an expectant patient suffering from a malignant disease: re-evaluation of nursing by reviewing the process record]. PMID- 2601157 TI - [Responses to the apprehension of an expectant patient suffering from malignant disease: with special reference to the basis of cancer nursing and preparation of a process record]. PMID- 2601158 TI - [Development of cancer in women: in relation to their life cycle]. PMID- 2601159 TI - [Midwifery education in France]. PMID- 2601160 TI - [Diagnosis of newborn infants. 4. Diagnostic methods and interpretation of the results]. PMID- 2601161 TI - [Interview with Ms. Ruth Rubic, President, Maternity Center Association, on the developing birth center activities based on family-centered care]. PMID- 2601162 TI - [Psychology of "Kiko", an ancient exercise method. 3. Listening to the wind]. PMID- 2601163 TI - [IUGR and current methods for the examination of blood flow]. PMID- 2601164 TI - [Current status and problems of obstetrical care]. PMID- 2601165 TI - [Medical care to meet the needs of expectant patients]. PMID- 2601166 TI - [New trends in childbirth and midwives. The goal of a midwives' study group organized for the study of childbirth]. PMID- 2601167 TI - [Childbirth without violence: for the welfare of infants. Practice of "super natural childbirth"]. PMID- 2601168 TI - [Current trends in childbirth and midwives. In place of home childbirth]. PMID- 2601169 TI - [Discussion on "sensitive midwifery": understanding of self and enhancement of sensitivity]. PMID- 2601170 TI - [Childbirth in the United States and recent developments in Japan]. PMID- 2601171 TI - [Diagnosis of newborn infants. 5. Interpretation of data on mothers and fetus]. PMID- 2601172 TI - [Midwives' suggestions for training of new graduates: based on the learning capacities and role learning of midwives]. PMID- 2601173 TI - [Survey on the attitude toward the presence of husbands at birth]. PMID- 2601174 TI - [Prognosis of IUGR]. PMID- 2601175 TI - [Psychology of "Kiko", an ancient exercise method. 3. Psychophysiological origin of illness]. PMID- 2601176 TI - [Research on the family in nursing. Factors of family which influence the anxiety of discharged patients]. PMID- 2601177 TI - [Research on the family in nursing. Social support related to recovery from grief caused by bereavement of spouse]. PMID- 2601178 TI - [Research on the family in nursing. Care of the family of the dying patient]. PMID- 2601179 TI - [Research on the family in nursing. Home care of old patients with sequelae of cerebral apoplexy]. PMID- 2601180 TI - [Family systems: values and value conflicts. New applications of the theory to clinical practice and in nursing education]. PMID- 2601181 TI - [The approach to the English monograph: to challenge your translation, to discover your mistakes (3)]. PMID- 2601182 TI - [Methods in classroom clinical training in pediatric nursing]. PMID- 2601183 TI - [Theories in classroom clinical training in pediatric nursing]. PMID- 2601184 TI - [Classroom clinical training in pediatric nursing at the Kanagawa Prefectural College of Hygiene]. PMID- 2601185 TI - [Ideal format for classroom clinical training in pediatric nursing: extraction of the subject and organization of specifics]. PMID- 2601186 TI - [Keypoints in clinical training using nursing processes]. PMID- 2601187 TI - [JNE news: revision of the curriculum for nursing education--reduction of the total hours to 3,000 hours (a 3-year course)]. PMID- 2601188 TI - [Exchanges between American nursing universities and the Kitasato University- toward establishment of a postgraduate nursing course in Japan (1). Visits to 4 nursing universities in the United States, the first visit to the U.S. as a preliminary study]. PMID- 2601189 TI - Cardiopulmonary fitness in a sample of Malaysian population. AB - Lung capacity and maximum oxygen uptake (VO2max) were measured directly in 167 healthy males, from all the main races in Malaysia. Their ages ranged from 13 to 59 years. They were divided into five age groups (A to E), ranging from the second to the sixth decade. Lung capacities were determined using a dry spirometer and VO2max was taken as the maximum rate of oxygen consumption during exhaustive exercise on a cycle ergometer. Mean forced vital capacity (FVC) was 3.3 +/- 0.5 l and it correlated negatively with age. Mean VO2max was 3.2 +/- 0.2 l.min-1 (56.8 +/- 3.5 ml.kg-1.min-1) in Group A (13-19 years) compared to 1.7 +/- 0.2 l.min-1 (28.9 +/- 2.9 ml.kg-1.min-1) in Group E (50-59 years). Regression analysis revealed an age-related decline in VO2max of 0.77 ml.kg-1.min-1.year-1. Multiple regression of the data gave the following equations for the prediction of an individual's VO2max: VO2max (l.min-1) = 1.99 + 0.035 (weight)-0.04 (age), VO2max (ml.kg-1.min-1) = 67.7-0.77 (age), where age is in years, weight in kg. In terms of VO2max as an index of cardiopulmonary performance. Malaysians have a relatively lower capacity when related to the Swedish norms or even to those of some Chilean workers. Malaysians were, however, within the average norms of the American Heart Association's recommendations. Age-related decline in VO2max was also somewhat higher in the Malaysians. PMID- 2601190 TI - Time-dependent effects of intrahypothalamic injection of vasoactive intestinal peptide on spontaneous motor activity in rats. AB - In male Wistar rats, microinjection cannulae were stereotaxically implanted in the ventromedial and paraventricular hypothalamic nuclei. After control recordings of spontaneous motor activity for 4-6 days, vasoactive intestinal peptide (VIP) was injected in a dose of 1.0 microgram and a volume of 2.0 microliters into these nuclei at 1100 or 1900 h, and the activity during the 3-h period following was compared with that on the control days in individual animals. VIP injection produced an increase when injected at 1100 h, and a decrease when injected at 1900 h. Thus, a time-dependent fluctuation in the VIP effect on the hypothalamic neuronal activity was suggested. PMID- 2601192 TI - Metabolic and blood pressure response to feeding activity is enhanced in freely moving spontaneously hypertensive rats. AB - Atrial temperature (Tat), heat production (M), mean arterial blood pressure (BP), and feeding (FA) and locomotor (LA) activities were measured over a 24-h period in spontaneously hypertensive rats (SHR) and their normotensive controls (Wistar Kyoto rats; WKY) at an ambient temperature of 24 degrees C. Clear day-night changes in all variables were observed in both groups except for BP and LA in SHR. During the day (0600-1800 h), SHR moved more frequently and seemed to eat more food than WKY. However, the total amount of food consumed for the 2 consecutive days was the same in both SHR and WKY. Compared with WKY, average M and BP during the day and at night and FA and LA during the day were significantly higher in SHR. The responses of Tat for a 24-h period, M during the day and for a 24-h period, and BP during the day to FA were significantly enhanced in SHR. There were no such significant differences of responses in Tat, M, and BP to LA between SHR and WKY. The results suggest that SHR is hyper responsive in metabolism and blood pressure to feeding activity, particularly in the daytime, but not to locomotion. PMID- 2601191 TI - Specific mitochondrial responses to running training are induced in each type of rat single muscle fibers. AB - The effects of training by running (sprint or endurance) on the mitochondrial volume, number, and succinate dehydrogenase (SDH) activity of different types of single muscle fibers, and on the elemental composition of soleus and extensor digitorum longus muscles were studied employing histochemical, electron microscopic, and electron probe-micro analysis (EPMA). Newly weaned male Wistar rats were trained on a motor-driven treadmill endurance exercise for 14 weeks. The relative mitochondrial volume per single muscle fiber of slow-twitch oxidative (SO) fiber was significantly increased following endurance training (p less than 0.01). There was no significant correlation between mitochondrial volume and number of SO fibers following endurance exercise training. Following sprint training, both mitochondrial volume and number of fast-twitch oxidative glycolytic (FOG) fibers increased significantly (p less than 0.01), with significant correlation (r = 0.69) between these parameters. SDH activity was higher in the order of SO, FOG, and fast-twitch glycolytic (FG) fibers following endurance training; however, the activity was higher in the order FOG, SO, and FG fibers following sprint training. The potassium concentration in cytoplasm of the soleus muscle showed a tendency to decrease following both types of training. These results suggest that the oxidative capacity of each type of muscle fiber does not always increase equally following training. Changes in mitochondrial number and volume in response to the two different types of training differed according to the type of fiber. PMID- 2601193 TI - Superior mesenteric sympathetic tone in conscious renovascular hypertensive rats. AB - Blood flow in the superior mesenteric artery was observed with a chronically implanted electromagnetic flow probe in two-kidney, one-clip renovascular hypertensive rats (2K1C), one-kidney, one-clip renovascular hypertensive rats (1K1C), and normotensive control rats (NCR) in the conscious state. Arterial pressure was recorded with an indwelling catheter. Superior mesenteric resistance was calculated as arterial pressure divided by superior mesenteric flow. In all three groups of rats, superior mesenteric resistance remained almost unchanged when arterial pressure decreased markedly on ganglionic blockade with hexamethonium bromide. However, subsequent injection of a vasopressin antagonist (Manning compound) decreased superior mesenteric resistance significantly in 2K1C but not in 1K1C and NCR. Injection of vasopressin antagonist alone was without effect on arterial pressure and superior mesenteric flow in the three rat groups. Only 2K1C were judged to have appreciable sympathetic tone in resistance vessels of the superior mesenteric area, which was blocked by hexamethonium but compensated for by secondarily secreted vasopressin. PMID- 2601194 TI - Potassium channel blockers inhibit anion secretion in cultured rat epididymal epithelium. AB - The effect of putative K channel blockers on anion secretion has been studied in primary monolayer cultures of rat epididymal cells using the short circuit current technique. Under basal conditions, monolayers had a transepithelial potential difference of about 2-3 mV, apical side negative and a short circuit current (SCC) of about 2 microA.cm-2. The transepithelial resistance was about 500 omega.cm2. Addition of adrenaline (0.23 microM, basolaterally) caused the SCC to rise to a peak value of about 10.5 microA.cm-2 and then stabilized at about 4 microA.cm-2 after 15 min. This rise in the short circuit current has previously been shown to be due to an increase in net anion secretion from the basolateral to the apical medium. In tissues stimulated with adrenaline, addition of barium (Ba) to the apical side did not affect the adrenaline-induced SCC, but addition to the basolateral side caused a dose-dependent inhibition of the current with an IC50 value (concentration required to inhibit 50% of the current) of 0.92 mM. At Ba concentration of 5 mM, the adrenaline-induced SCC was completely abolished. There was no effect on transepithelial resistance. Addition of tetraethylamonium (TEA) (16 mM) to the apical or basolateral side had no significant effect on the adrenaline-stimulated SCC. Lidocaine and quinidine inhibited the adrenaline stimulated SCC when added either to the apical or basolateral bathing solution. The IC50 values for lidocaine were 0.42 mM and 0.35 mM for basolateral and apical application, respectively. The IC50 values for quinidine were 0.062 mM and 0.050 mM for basolateral and apical application, respectively. In all cases there was no change in tissue resistance. It is proposed that in the basolateral membrane of the epididymal cells, there is a component which is sensitive to putative K channel blockers. It is likely that it is a K channel. As in other secretory cells, this channel plays an important role in secretion. PMID- 2601195 TI - Shrinkage of rat mandibular acinar cell with acetylcholine detected by video enhanced contrast microscopy. AB - Changes in acinar cell volume during secretion were observed in the perfused rat mandibular gland by the video-enhanced contrast (VEC) microscopy. The acinar cell shrank (81.3 +/- 4.9% (mean +/- S.D., n = 5] during acetylcholine stimulation and swelled (107.4 +/- 2.3% (n = 5] after cessation of the stimulation. These evidences suggested that a large amount of fluid is transported via transcellular route in the salivary gland. PMID- 2601196 TI - Change in surface charge of sarcoplasmic reticulum membrane may elicit conformational change in sulfhydryl groups of membrane proteins to release calcium. AB - A lipophilic anion, tetraphenylboron (TPB-)-induced Ca2+ release from fragmented sarcoplasmic reticulum (SR) of frog skeletal muscle was monitored by chlortetracycline fluorescence. TPB- caused change in surface charge of the membrane and in the protein conformation with a time course similar to that of the Ca2+ release. Tetraphenylarsonium (TPA+) inhibited these effects of TPB-. Change in surface charge of SR is suggested to cause conformational change in SR membrane proteins, and then result in Ca2+ release from the SR. PMID- 2601197 TI - [An examination of the emotional meanings through hand movements]. AB - In this study, emotional meanings associated with hand movements were investigated. All hand movements were performed by a female subject who was asked to use her right hand in such a way as to exclude cues from other forms of bodily communication such as those arising from facial expressions, gestures and various body postures. Seven kinetic variables relevant to hand movements were identified and 708 stimulus pictures were developed and presented to 115 male and 105 female subjects for evaluation using a 28 affect adjective check list. A varimax rotated factor analysis applied to the data yielded three factors for each sex as follows: (1) positive affect, (2) negative affect and (3) arousal. For female subjects, a fourth factor--"surprise"--was also identified. Examination of factor scores suggested that positive affect was related to an outside location of the arm, or upper spatial orientation, and to extension of the fingers. In contrast, negative affect was associated with an inside location of the arm and a clenched fist. Arousal was found to be related to palmar flexion and a clenched fist directed to the outside. Finger abduction and the elbow bent toward the outside were associated with the factor of "surprise" in females. PMID- 2601198 TI - [The influence of musical experiences on discrimination of two-pure-tone simultaneous intervals]. AB - The purpose of this study was to examine whether experiences of musical instruments influence on discrimination of two-pure-tone simultaneous intervals. Fifteen experienced and 14 inexperienced subjects were asked to compare a standard stimulus with a comparison stimulus whose lower tone was varied from -4 Hz to +4 Hz, and to judge whether they were same or different. One single tone and four two-pure-tone simultaneous intervals, major second, major third, perfect fifth, and major seventh were used as stimuli. The results showed that the experienced subjects were generally more accurate and quicker in the task than the inexperienced subjects. It was suggested that a schema for discrimination of two-pure-tone simultaneous intervals was formed by exercises on musical instruments, and that the inexperienced subjects also had the schema to some extent. PMID- 2601199 TI - [Sequential fluctuation of conformity and fixation of escape behavior in an emergency, with a mathematical model]. AB - First, all subjects were shown the process of escape behavior of other four subjects (comrades) concentrating to one of five routes, then they were told that they should decide whether to change escape route or persist to that route. During observation of comrades' behavior, the subjects were free to decide whether to change the route or not. The results indicated that conformity levels fluctuated according to the feedback from the others' behavior. This fluctuation was explained using a Markov model. According to this model, the transitional probability, which consists of that factors of conformity, fixation and preference, depend on information concerning others' behavior were made available. PMID- 2601200 TI - [A examination of conversation process in social context]. AB - The purpose was to reveal a set of conversation rule and to examine the effect of social context on the importance of the rule. We collected 51 items concerning conversation rule from 29 male and female undergraduates. Another 128 male and female undergraduates were asked to rate the importance of each item in given social contexts. We manipulated three factors of (a) goal orientation in conversation, (b) intimacy of a dyadic relationship, and (c) combination of sex, in the descriptions of the social contexts. Factor analysis of the rating scores led to identification of six factors of conversation rule: 1) acceptance rule, 2) rule for partner, 3) rule for accomplishment of speech, 4) rule for intention of speech, 5) emotion-directed expression rule, 6) comprehension-directed expression rule. The results of ANOVA indicated that the importance of each factor varies with social context. PMID- 2601201 TI - [Effects of choosing a task on interpersonal feeling and appreciation]. AB - From the viewpoints of relative deprivation and social comparison jealousy, this article reports on a study that investigated the effects of choice on subsequent appropriate feeling and appreciation for another person who is superior to subjects in the same or different field. A 2 x 2 between-groups design was used to determine the effects of choice (present or absent) and field (same or different). Individual differences were assessed by using three scales: Self Esteem, Self-Monitoring, and Social Desirability. Forty-one male subjects participated in a task and received negative feedback, and then evaluated a superior on both pencil and paper and bogus-pipeline (BPL) measures. Most importantly a significant Choice x SE interaction was obtained on BPL: It means that through experiencing choice the high Self-Esteem subjects can maintain appropriate feeling and appreciation even on BPL although some self-presentation is inevitable. PMID- 2601202 TI - [An attempt to construct the Sensation Seeking Scale-Abstract Expression]. AB - The purpose of this study is to construct Sensation Seeking Scale-Abstract Expression (SSS-AE), consisting of 15 items. All items were described in relatively abstract terms. Data were collected from Japanese college students (246 males and 121 females). The total SSS-AE scores had positive correlation with the general factor of sensation seeking. This confirms the validity of the SSS-AE proposed in this study. From the factor analysis of the items, three factors were extracted: Thrill and Adventure Seeking (TAS), Disinhibition (Dis), and Experience Seeking (ES). But Boredom Susceptibility (BS) was not confirmed. These results were discussed in comparison with the factors reported by Zuckerman. Males showed higher ES scores than females, but females showed higher Dis scores than males. PMID- 2601203 TI - [A longitudinal study of university students' identity dimension development]. AB - One hundred and twenty-five freshmen in an education/psychology department t. (56 males and 69 females) and 63 psychology major juniors of the same department. (27 males and 36 females) were administered an identity dimension (ID) scale and a questionnaire on crises and commitments in 11 areas during June 1984. Surveys were repeated with these subjects on February and June '85, and February '86. The principal results were as follows: (a) the number of high ID score students increased in junior and senior years; (b) ID scores were distributed in a two peaked form at graduation; (c) female subjects' levels of crises with 'same-sex friends', 'opposite-sex friends', and on 'study' decreased corresponding with the increase of ID scores; male subjects' levels of crises with 'opposite-sex friends' and on 'desirable life styles and values' increased corresponding with the decrease of ID scores. PMID- 2601204 TI - [Effects of the intensity of unstable status structures on the powerholders' power maintaining tendency]. AB - The purpose of the present study was to investigate effects of the intensity of unstable status structures on the powerholders' power maintaining tendency. In advance aptitude test was administered to the subjects (24 male undergraduates). Each subjects was led to believe that he was screened and supervised four performing groups as a powerholder (Top-leader). Each subjects was also assigned to either the status change condition (12 males) or the non status change condition (12 males). The following results were obtained. Compared to the powerholders under the non status change condition, the powerholders under the status change condition (1) evaluated less subleaders' contributions to the high performance group, (2) gave more difficult tasks to the high performance group. These results were compared with the study by this author (1987) and discussed in terms of the relation between the power maintaining tendency and intensity of unstable status structures. PMID- 2601205 TI - [Deficits in radial-arm maze learning in aged rats]. AB - The present study was designed to investigate the possible deficits in the place learning on the 8-arm radial maze in aged rats. In this task, reward was given in the 4 predetermined arms. Aged rats (27 months old, N = 7) acquired this task more slowly than young rats (12 months old, N = 11), and didn't reach to the performance level of the young rats within 80 training trials. Analysis of error choices revealed that the aged animals first entered in the unbaited arms more often than the young rats, whereas there was no difference in the number of re entered choices to the baited and unbaited arms between the aged and young animals. Therefore, it was concluded that learning deficits in aged rats were attributed to deficits in the reference memory but not in the working memory. PMID- 2601206 TI - [Focal points and methods in the evaluation of home care activities]. PMID- 2601207 TI - [Evaluation of home care of the aged]. PMID- 2601208 TI - [Evaluation of home care of people who are highly dependent on medical care: with special reference to public health nursing activities]. PMID- 2601209 TI - [Evaluation of home care systems by regional comparison]. PMID- 2601210 TI - [Nursing in daily activities. 27. Communication (1)]. PMID- 2601211 TI - [Medical checkup of the aged. 16. Ophthalmology (1). Aging of the eye]. PMID- 2601212 TI - [Evaluation of nursing assistance of the aged being cared for at home and their families]. PMID- 2601213 TI - [Evaluation of the functions of the home care system based on case studies]. PMID- 2601214 TI - [The role of public health nurses in the home care support system: at a model facility in Nagoya City]. PMID- 2601215 TI - [Reduction of urinary oxalate excretion by administration of calcium and citrate]. AB - Oxalic acid seems to be more important for the formation of calcium oxalate stone than calcium. Three grams of calcium lactate and 3 g of uraly U were administered to 35 urolithiasis patients, whose stones were mainly composed of calcium oxalate. Urinary oxalate level was reduced significantly without raising urinary calcium level by the administration of the two drugs for two weeks. The reduction of oxalic acid was particularly remarkable in patients without hypercalciuria. The mechanism of action of these drugs and the relation to dietary management were discussed. PMID- 2601216 TI - [Immunohistochemical study of tissue polypeptide antigen (TPA) in human urinary bladder tumors]. AB - The immunohistochemical study of tissue polypeptide antigen (TPA) was performed by Avidin-Biotin-Peroxidase complex method (ABC method) in the human bladder tumors. Thirteen bladder tumors (4 cases with transitional cell carcinoma grade 1, 6 cases with grade 2 and 3 cases with grade 3; 7 cases with pTa, 3 cases with pT1 and 3 cases with pT3) were subjected to this study. Prior to the experiment, it was confirmed that the TPA reactivity was not diminished by the tissue fixation with buffered formalin within 72 hours. Bladder tumors of grade 1 and 2 were strongly stained for TPA, whereas bladder tumors of grade 3 appeared to be stained weakly. There were no relationships between TPA stainings and the tumor staging, and between the TPA stainings and the prognosis of the patients. We have concluded that the TPA staining might be a useful method for determination of the bladder tumor grading. PMID- 2601217 TI - [An electromyographic study of detrusor sphincter dyssynergia in the neurogenic vesical dysfunction. Part 1. Its type and further sub-typing based on the analysis of motor units]. AB - Simultaneous recordings of electromyography of the external urethral sphincter (EUS) and bladder pressure were performed in 73 patients. The majority (69 cases) were afflicted with neurogenic vesical dysfunction, while four with benign prostatic hypertrophy (BPH) were also examined as control. Detrusor sphincter dyssynergia (DSD), whereby EUS failed to relax on voiding attempt, was noted in 64 patients. By examining the patterns of DSD throughout the voiding, it was possible to classify them into three distinct types as done by Blaivas. Type 1 was found in 7 patients, Type 2 in 10 patients, and Type 3 in 47 patients. Synergic urethral sphincter activity (Type 0) was found in other 9 patients including all four with BPH. Voiding dysfunction as evaluable by residual urine rate tended to increase as the type deteriorated from 1 to 3. Analysis of motor units revealed that the units noted during continent phase of the bladder disappeared (A0), decreased (A1), and retained or rather increased their activity (A2) during voiding attempt with (B1) or without (B0) recruitment of new units. A0B1 was found in 3 patients, A1B1 in 7, A2B1 in 32, A2B0 in 4, and A1B0 in 2. Again there was a tendency for voiding function to deteriorate as motor units sub type changed from A0 to A1 and A2. The analysis of these motor units activities suggested that abnormal continence reflex (i.e. failure of vesicourethral and urethrourethral relaxation reflex and exaggeration of urethrourethral contraction reflex) might be contributing to the genesis of DSD. PMID- 2601218 TI - [Comparative study on prophylactic intravesical instillation of bacillus Calmette Guerin (BCG) and adriamycin for superficial bladder cancers]. AB - In this study we evaluated 77 patients with superficial bladder cancer who were treated with either intravesical bacillus Calmette-Guerin (BCG) (44 patients) or doxorubicin hydrochloride (Adriamycin, ADR) (33 patients) for prophylaxis of tumor recurrence after transurethral resection. The estimated actuarial probability of non-recurrence rate at three years for the BCG group was 73.0%, and the actuarial non-recurrence rate for the ADR group was 27.3%; a statistically significant difference (p = 0.0013). A comparison between the two groups was also made according to the patient's background, including whether the tumor was initial or recurrent, solitary or multiple, and the tumor grade. In all areas of the study, except for grade-1 tumors, the BCG group was significantly superior to the ADR group. The efficacy of BCG therapy as a result of different BCG treatment protocol was evaluated for six weekly instillations 1) without further maintenance instillation, 2) followed by 12 months of maintenance, and 3) followed by more than 18 months of maintenance. Long-term maintenance BCG instillation group (more than 18 months) showed the most favorable results, however, the differences were not statistically significant. These results indicate that intravesical BCG instillation was significantly superior to ADR in the prevention of bladder cancer recurrence and that six weekly intravesical BCG instillations may provide adequate prophylactic effects against recurrence of superficial bladder cancers. PMID- 2601219 TI - [A study of urinary incontinence after prostatectomy]. AB - With respect to prostatectomies carried out in clinic since the opening of the Kinki University Hospital in 1975, incontinence after prostatectomy was investigated with 470 patients as subjects for whom a follow-up study after the operation was possible. Also, the usefulness of the urodynamic tests for diagnosing underlying diseases was investigated. 1) Overall incidence of incontinence after transurethral resection of the prostate (TUR-P), retropubic prostatectomy (RPP) and cryoprostatectomy was 5.7 percent. 2) The incidence of incontinence was 7.1 percent of the patients with TUR-P and 3.5 percent of patients with RPP. The incidence of incontinence after cryoprostatectomy was none. 3) There was no clear differences among the incidence of incontinence after prostatectomy and the weight of resected tissues. 4) There was no clear differences among various types of incontinence after each procedures of prostatectomies. 5) The incontinence was satisfactorily treated and disappeared in 18 patients within one year after the operation. In patients who failed to get continence within a year, the incontinence was likely to persist furthermore. 6) The cure rate was low in patients with abnormal findings in a cystometrogram performed prior to the operation. Associated diseases which could cause disorders in nervous system were frequently encountered in such patients. 7) Drugs and functional electrical stimulation (FES) were introduced for the treatment of incontinence after prostatectomy. FES was effective in 36.4 percent in which drug therapy was not effective. Since multiple drug regimen was administered in most of the patients, it was difficult to make a precise evaluation of judgement for effect of each of drugs. PMID- 2601220 TI - [Mechanical property of the human ureter]. AB - This paper is the 10th report in a series of studies on the application of microexplosion to medicine and biology. In the application of microexplosion for destruction of ureteral calculi, the mechanical property of the ureter is an important factor for the prevention of complication. To clarify the factor in humans, tensile and expansive tests were performed on the middle portion of the normal ureter taken from fresh cadavers. Tensile test: Tensile test was performed using 11 ureters in the longitudinal direction and 7 in the transverse direction. 1) In the both directions a 3-phase curve was obtained between the elongation of the specimen and the load, turning at the two yield points. It was presumed that a small part of the mural element of the ureter was first torn at the first yield point, then all the element followed at the second point. 2) At the each yield point the tensile strength and maximum tensile stress of the transverse direction of the ureter were weaker than those of the longitudinal direction, although the elongation ratio at the two yield points was similar in the both directions. It was presumed, accordingly, that ureteral injury first occurred in the transverse direction. 3) The maximum tensile stress of the ureter was higher than that of the bladder. Expansive test: Expansive test was performed using 10 ureters. 1) At a leakage point, the internal pressure of the ureter was 1.9 kgf/cm2 and the internal diameter was 6.4 mm on average. 2) At the leakage point, the tensile strength and elongation ratio of the external diameter were 0.71 kgf/cm and 0.80 on average, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601221 TI - [Investigation of factors affecting the progression of polycystic kidney disease and effects of percutaneous reduction of cystic size]. AB - Factors affecting the progression of autosomal dominant adult type polycystic kidney disease were analysed in 27 cases. The patients ages ranged from 10 to 74 (mean 44) years old and the serum creatinine values were within the normal limits except two cases, in which the values were 2.4 mg/dl and 2.1. They were followed for from 2 years to 12 years (mean 5.6 years). During the followup period, 6 cases showed elevation of the serum creatinine values and hemodialysis was necessary in 4 cases. There was a tendency of higher morbidity rate of hypertension, proteinuria, hematuria and pyuria in the cases with decreased renal function. These factors may have participated in the progression of polycystic kidney disease. Cystic fluid analysis was performed by percutaneous puncture of more than hundred cysts in 27 cases. The results showed that the cystic fluid components of most cysts of the well functioning kidneys were similar to those of serum values: so-called proximal cysts. On the other hand, in the cases with decreased renal function, there were many cysts with lower sodium concentration and higher creatinine values: so-called distal cysts. The results suggest that the existence of so-called distal cysts may indicate poorer prognosis. DMSA renoscintigraphy was useful for followup polycystic kidney patients because of the uptake of the radionuclide was decreased before rising the serum creatinine value. In 6 cases, the cysts were instilled with 95% ethanol. Followup ultrasonography and DMSA renoscintigraphy revealed a marked reduction of the cystic size and an improvement of DMSA uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601222 TI - [Pathomorphological study of local extension and progression of prostate cancer]. AB - The interrelationship among localization of tumor, local extension, lymph node metastasis and various histological grades was investigated in 31 consecutive series of prostate cancer treated by radical prostatectomy. Surgical specimens were examined by step sections cut perpendicular to the urethra. Each tumor was graded histologically in accordance with WHO-Mostofi grading (evaluated by nuclear anaplasia and structural differentiation), Gleason's and M.D. Anderson's grading systems. The areas of the prostate was divided into 4 quadrants delimited vertically along the urethral axis and transversely at the level of utricle, i.e. anterior/superior, anterior/inferior, posterior/superior and posterior/inferior quadrants. Topographical localization and extension of each tumor was examined in accordance with the above area subdivision. Every tumor was growing at least in the posterior/inferior area. All cases with tumor progression to the anterior/superior area also revealed extensive tumor growth in the other two or three quadrants. Therefore, prostate cancer appears to be originated from the posterior/inferior area of the prostate and terminated in the anterior/superior area as local extension. In 31 cases examined, capsular invasion was noted in 22, seminal vesicle invasion in 16, and lymph node metastasis in 12 cases. All cases with seminal vesicle invasion also showed capsular invasion. None of the cases without capsular and/or seminal vesicle invasion had lymph node metastasis. Thus, it is inferred that prostate cancer is initially growing locally, extending to the capsule and seminal vesicle and then metastasizes to the pelvic lymph nodes. As for the histological grading, higher grade tumors tended to show higher incidence of capsular and seminal vesicle invasion and lymph node metastasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601223 TI - [Expression of myc family oncogenes in primary human testicular cancer]. AB - In order to understand the role of myc family genes (c-myc, N-myc and L-myc) in the development and progression of human testicular cancer, we have analyzed the expression of myc family genes in three different types of primary human testicular cancer (seminoma, embryonal carcinoma and teratocarcinoma) and normal testis using Northern blot analysis. Expression of N-myc gene, which is usually limited in the neoplasms derived from neuroectoderm, was detected in seven out of ten cases of seminomas and two out of two cases of embryonal carcinomas. Gene amplification was not observed in these cases. Expression of N-myc gene was not detected in teratocarcinomas and normal testes. Expression of c-myc gene was observed in seminomas, embryonal carcinomas, teratocarcinomas and normal testes, but specific expression of c-myc gene was not seen in these cancers and normal testes. Expression of L-myc gene was not detected in all cases examined in our studies. Since N-myc gene expression was observed only in undifferentiated testicular neoplasm, such as seminoma and embryonal carcinoma, its expression may be positively related to the development and progression of special types of human testicular cancer. PMID- 2601224 TI - [Partial remission of pulmonary metastasis of malignant gonadal stromal tumor by salvage chemotherapy]. AB - Fourteen malignant cases of gonadal stromal tumor were found among the cases reported in literature, but the roles of chemotherapy and radiotherapy have not been defined. We treated a malignant case and achieved 98.9 per-cent remission of lung metastases by salvage chemotherapy (cis-platinum + VP-16). A 34 year-old desk-worker, underwent left orchiectomy for testicular tumor on March 20, 1984. Histologic examination showed a malignant gonadal stromal tumor invading into the epididymis. Three course of adjuvant chemotherapy with cis-platinum, vinblastine, and peplomycin (PVP) were performed. However, chest X-ray films 13 months later revealed multiple lung metastases. Although 3 courses of combination chemotherapy with cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) were given, no remission was obtained. However following 4 courses of combination chemotherapy with cis-platinum and VP-16, 98.9 per-cent remission of lung metastases was achieved. Subsequent bilateral residual lung tumors were resected. However, lung metastases recurred 3 months later, and the patient died on February 29, 1988. The autopsy revealed extensive lung, liver and pancreas metastases, but no lymph node metastases. PMID- 2601225 TI - Induction of lipid peroxidation in mice by hexavalent chromium and its relation to the toxicity. AB - Comparative effects of hexavalent (K2Cr2O7:Cr(VI)) and trivalent chromium (Cr(NO3)3:Cr(III)) on the development of lipid peroxidation, and the relationship between the lipid peroxidation and damage to tissues were studied using male ddY strain mice. The animals were administered with either of two chemicals at a dose of 20 mg Cr/kg by a single intraperitoneal injection. The results obtained were as follows: (1) Lipid peroxidation in the liver, as measured by the synthesis of thiobarbituric acid reactive substances (TBARS), showed a significant increase at 24 and 48 hr after Cr(VI) injection, while in the kidney it was observed only at 48 hr. In the mice administered with Cr(III), TBARS formation in the liver went down below the control levels, while no change was observed in the kidney. (2) Chromium contents in the liver and kidney showed a maximum level at 6 hr after injection of Cr(VI) and then those declined to the half of the maximum level at 48 hr, respectively. Chromium contents in the liver and kidney of the mice injected with Cr(III) were lower than those injected with Cr(VI) during the experimental period. (3) Increases of TBARS formation in the liver, chromium content in the liver and kidney, and ornithine carbamyl transferase (OCT) activity indicative of the liver cell damage, and urea nitrogen content in the serum, indicative of the kidney damage, observed at 24 hr after injection of Cr(VI) were inhibited by simultaneous injection of 100 mg/kg of L-ascorbic acid, as antichrome agent, respectively. These observations might suggest a possible causative role of lipid peroxidation in Cr(VI) toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601226 TI - Development of Babesia ovata in the midgut of the tick, Haemaphysalis longicornis. AB - Studies were made on the development of Babesia ovata in the midgut of the nymphal tick vector, Haemaphysalis longicornis. In 12 hr post-repletion, merozoites were observed outside of erythrocytes infected with B. ovata in the contents of the midgut of the tick. After that, these merozoites were transformed into ring-forms which were comparatively large ring 2-3 microns in diameter. Within 48-72 hr post-repletion, ring-form protozoa developed into spherical form 4-5 microns in diameter. Within 3-4 days post-repletion, fission-forms were transformed into fission-bodies 2-3 microns in diameter. Within 4-6 days post repletion, fission-bodies developed into bizarre-forms 6-7 microns in diameter. At this time, elongated form protozoa which were considered as microgametes, 6-8 microns in length, are also seen. Within 6-8 days post-repletion, round-formed protozoa which were considered as zygotes in 9-10 microns in diameter were observed in the gut. About 10 days after repletion, those round-formed protozoa were transformed into vermicule-formed and round-formed protozoa, 13-15 microns in length, appeared again in the gut epithelial cells. PMID- 2601227 TI - Epidemiological study on periodontal diseases and some other dental disorders in dogs. AB - The prevalence of dental disorders in dogs was studied by applying index systems for human with some modifications. A total of 251 mongrel dogs including 143 stray dogs kept in the Animal Protection Offices in Tokyo and Hokkaido and 108 pet dogs visiting veterinary clinicians in Chiba Prefecture and Hokkaido were used. Periodontitis was prevalent among these dogs regardless of their sources and its incidence was increased with age. The lesion was more severe and more frequent in the premolar and molar regions than in the maxillary and mandibular incisor regions. Missing of teeth was observed at a high and increasing incidence with age. The tooth most commonly lost was the first premolar, followed by the other premolars and molars, where severe periodontitis was frequently found. Calculus was seen on many teeth, and aging agravated its prevalence and severity. Dental caries was observed in stray dogs, but neither to a serious degree nor at a significant level. These findings emphasize the necessity of dental hygiene, proper dental care and continuous periodical survey for dogs. PMID- 2601228 TI - Morphology of blood cells in carp (Cyprinus carpio L.). AB - The morphology of blood cells in the carp was investigated by light and electron microscopy. Erythrocytes, thrombocytes, lymphocytes, granulocytes and monocytes were identified as the peripheral blood cells. Thrombocytes were round to long oval, each containing vesicular and microtubular structures and an oval nucleus with abundant heterochromatins. Lymphocytes were divided into three types in size, small, medium and large. Some of the small and medium lymphocytes were alpha-naphthyl-acetate esterase (ANAE) positive, while large lymphocytes were pyroninophilic. Granulocytes were distinguished into three types (type I, type II and type III) according to the morphology of the nucleus and granules. Type I granulocytes possessed lobulated nuclei and a large number of cytoplasmic granules, each of which was oval and contained electron-dense materials and a crystalloid. Type II granulocytes had small eccentric nuclei and were subdivided into IIa and IIb granulocytes by electron microscopic analysis. Granules of type IIa granulocytes were furnished with an electron-dense rim. Granules of type IIb granulocytes were larger than those of type IIa, containing randomly distributed electron-dense and electron-lucent materials. Type III granulocytes possessed round nuclei and a few large granules. The granules were filled with regularly arranged fibriform materials and some needle-like structures. Monocytes were morphologically similar to those of mammals. PMID- 2601229 TI - Studies on route of immunization with a mixture of killed parasites and adjuvants against Babesia rodhaini infection in mice. AB - A series of experiments were undertaken to determine the most effective route of immunization with a mixture of killed Babesia rodhaini antigen (S antigen) and formalin-fixed Corynebacterium parvum (Propionibacterium acnes) bacterin (CPB) against challenge infection with B. rodhaini 3 weeks later. The mice pretreated with S antigen and CPB mixture intraperitoneally, but not intramuscularly, were significantly resistant to intraperitoneal (IP) or intravenous (IV) challenge with 10(6) organisms. The survival rates were 70.0 (IP challenge) and 60.0% (IV challenge) respectively. Fairly protective activities were equally produced in mice intravenously pretreated with S antigen and CPB with survival rates of 60.0% against IV challenge, but 30% against IP. These results indicated that the IP injection of S antigen and CPB mixture is desirable route for immunization against subsequent IP or IV challenge with B. rodhaini. On the other hand, lower protective effect was reconfirmed in the mice treated with S antigen and Freund's Complete adjuvant, regardless of immunization routes in the additional experiment. The survival rates were 33.3, 14.3 and 11.8% in the intraperitoneally, intramuscularly and subcutaneously-treated mice respectively against IP challenge with 10(6) organisms. PMID- 2601230 TI - Effect of pregnancy on gravid sclerosis of bovine uterine arteries. AB - Gravid sclerosis of the uterine artery was histologically examined in multiparous cows. This sclerosis was characterized by a thickening of the intima and a lamination of the internal elastic lamina. It was clearly observed at non pregnant and early-pregnant stages and in the late postpartum period, but it could not be detected at term-pregnant stages and in the early postpartum period. These results suggest that the gravid sclerosis disappears during pregnancy and re-establishes after parturition. The importance of local factors, e.g. hemodynamics, in the cyclic appearance of gravid sclerosis is discussed. PMID- 2601231 TI - Isolation and monolayer culture of bovine oviduct epithelial cells. AB - Oviduct epithelia obtained from 32 cows were cultured. The oviducts were classified into follicular and luteal phases and divided into ampulla and isthmus regions. The epithelial cells were dissociated by enzyme digestion and cultured in plastic dishes with Dulbecco's modified Eagle's medium/Ham's F12 (1:1) containing 10% calf serum. After enzyme treatment, the epithelial suspension showed free ciliated and non-ciliated cells, and cell mass. The non-ciliated cells contained secretory granules in the cytoplasm. The cell mass was composed of ciliated and secretory cells. The cell mass adhered to the dish within 12-24 hr, while the free ciliated cells attached on Day 2 of the culture. The cells grew into confluent monolayers on Day 4. The cell monolayers contained ciliated and non-ciliated cells. The monolayered non-ciliated cells showed a few secretory granules. When the cells were further cultured without subculturing, ciliary activity diminished on Day 5 and was rarely detected on Day 9. When the cells were subcultured on Day 3, ciliary movement was detected on the monolayers for only 2 days. Cell mass that did not adhere to the dish and remained floating in the medium formed ball-like structures on Day 2. Active ciliary beating was observed on the cells that were cultured in the medium supplemented with 10(-5) and 10(-9) M estradiol-17 beta, however, the ciliary activity diminished on Day 5. No difference in the cell growth was observed between the follicular and luteal phases or between the ampulla and isthmus regions. PMID- 2601232 TI - Surgical treatment of priapism observed in a dog and a cat. PMID- 2601233 TI - Ultrastructure of spontaneous degenerative lesions in the tongue of DBA mice. PMID- 2601234 TI - Yolk sac carcinoma in a B6C3F1 mouse. PMID- 2601235 TI - Detection of serum antibodies of oral Porphyromonas (Bacteroides) asaccharolyticus in dogs: relationship to periodontal disease. PMID- 2601236 TI - Seasonal changes in the phospholipids and fatty acid composition of the bovine erythrocyte membrane. PMID- 2601237 TI - Effect of Corynebacterium parvum bacterin on artificial immunity against Babesia rodhaini infection in mice. PMID- 2601238 TI - Canine distemper virus infection in lesser pandas (Ailurus fulgens). PMID- 2601240 TI - Isolation of Actinobacillus (Haemophilus) pleuropneumoniae from pneumonic lungs of slaughtered pigs. PMID- 2601239 TI - Different protein patterns in normal and mastitic milks as revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. PMID- 2601241 TI - Enhancement of neutrophil function by dihydroheptaprenol in adult cows. PMID- 2601242 TI - Don't parameter me in. PMID- 2601243 TI - Overseas elective in Rwanda. AB - The experience at Kibogora was professionally and personally rewarding. I obtained hands-on training in a variety of procedural skills and exposure to tropical medicine and treatment of infectious diseases. I developed a respect and affection for the Rwandan people and for the missionaries and their families. The experience solidified my desire to make medical missions a part of my life. PMID- 2601244 TI - Antipurkinje cell antibodies in cerebellar degeneration. PMID- 2601245 TI - Emergency use of intraosseous infusions. PMID- 2601246 TI - [HIV/AIDS today]. PMID- 2601247 TI - [Personality limitations and possibilities in midwifery]. PMID- 2601248 TI - Nursing is at war! PMID- 2601249 TI - The anatomy of creativity. PMID- 2601250 TI - Nursing creativity through art. PMID- 2601251 TI - Renal kallikrein responses to dietary protein: a possible mediator of hyperfiltration. AB - We studied GFR, RPF and renal kallikrein in rats fed 9%, 25%, or 50% protein (casein) diets for 8 to 13 days. CFR and RPF increased progressively with increasing dietary protein. Renal excretion of active kallikrein (microgram/day) was 128 +/- 9, 174 +/- 11 and 228 +/- 14 in 9%, 25%, and 50% protein-fed rats, respectively (P less than 0.02 or less between groups). Prokallikrein excretion in these groups was 23 +/- 7, 77 +/- 11 and 118 +/- 15 micrograms/day, respectively (P less than 0.005 or less between groups). The in vivo renal kallikrein synthesis rate, relative to total protein synthesis, was reduced in 9% protein-fed rats (2.74 +/- 0.24) compared to rats fed 25% (3.93 +/- 0.34, P less than 0.02) or 50% protein (4.41 +/- 0.30, P less than 0.001). These changes in synthesis and excretion rates were not accompanied by changes in renal tissue levels of active or prokallikrein. In all groups, GFR and RPF correlated directly with the renal excretion of active kallikrein, prokallikrein or total kallikrein (r = 0.41 to 0.66, P less than 0.01). Treatment of 50% protein-fed rats with aprotinin, a kallikrein inhibitor, markedly lowered renal and urinary kallikrein like esterase activity. Left kidney GFR and RPF were significantly reduced in aprotinin-treated rats compared to vehicle-treated rats (1.54 +/- 0.15 and 4.86 +/- 0.38 ml/min vs. 1.89 +/- 0.10 and 5.93 +/- 0.22 ml/min, GFR and RPF, respectively, P less than 0.05 or less).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601252 TI - Urinary excretion of glycosaminoglycans in normal and stone forming subjects. AB - There is evidence suggesting that glycosaminoglycans (GAG) are potent inhibitors of growth and aggregation of calcium oxalate crystals in vitro. This finding raises the possibility that the urinary GAG could play an inhibitory role in the urolithiasis. To investigate this hypothesis, a study on the urinary excretion of GAG in normal and stone forming adults and children was undertaken. Different methods were compared, and the best results were obtained when the GAG were measured by densitometry after agarose gel electrophoresis. Although the GAG concentration was increased in the morning urine compared to the 24-hour urine samples, and in males compared to females, the GAG/creatinine ratio was independent of period of urine collection and of sex. So, it was advantageous to express the amounts of urinary GAG as mg/g of creatinine. Children excreted more GAG than adults, with a higher proportion of chondroitin sulfate. We have shown that the stone forming subjects, both adults and children, excreted lower levels of urinary GAG as compared to normal subjects, independently of the metabolic disorder. The proportions between chondroitin sulfate and heparan sulfate and the structures of these GAG were unaltered in the stone formers. These results indicate that there is a definite difference in terms of levels of GAG between normal and stone forming urines, and suggest a correlation between the urinary GAG concentration and urolithiasis. PMID- 2601253 TI - Platelet activating factor is produced during infectious peritonitis in CAPD patients. AB - Peritonitis, a frequent complication of continuous ambulatory peritoneal dialysis (CAPD), is a model of inflammation which provides the opportunity to recover the exudate fluid. To date, various endogenous mediators (histamine, bradykinin, activated complement factors, prostanoids) have been implicated in the mediation of peritoneal inflammation and increased peritoneal permeability. In the present study, a lipid compound with physicochemical and biological characteristics similar to platelet activating factor (PAF) (1-0-alkyl-2-acetyl-sn-glyceryl-3 phosphorylcholine) was extracted in significant amounts from the dialysate of eight out of nine peritonitis episodes in seven CAPD patients (Group A; 6771.4 +/ 3025.9 pM, mean +/- SEM at the first exchange during peritonitis). The amounts of PAF recovered in the first exchange dialysate from patients of Group A were linearly correlated with the loss of albumin (y = -3157.64 + 91.4x; r = 0.7394; N = 9; P less than 0.03) and number of leukocytes (y = 902.45 + 1.52x; r = 0.7576 N = 9; P less than 0.02). PAF was not detectable in the dialysate fluid from patients of Group A after recovery. Twelve patients on CAPD who had no past or present history of peritonitis (Group B) were used as controls; no PAF (9 patients) or only minimal amounts (3 patients: 7.0 pM; 23.0 pM; 70.0 pM) of this mediator were detected. This is the first direct demonstration of the local generation of PAF in a septic inflammatory reaction involving the peritoneal serosa in man. PAF produced by various cell types (neutrophils, peritoneal macrophages, endothelial cells) during peritoneal inflammation may contribute to the increased permeability of the peritoneal vascular bed. PMID- 2601254 TI - A single nephron model of acute tubular injury: role of tubuloglomerular feedback. AB - A single nephron model of nephrotoxic tubular injury was established to examine the mechanism whereby acute tubular damage contributes to reductions in nephron filtration rate (SNGFR). Acute microperfusion of 0.5 ng of uranyl nitrate (UN) into the early proximal tubule produced a significant reduction (16 to 30%) in SNGFR measured in both distal and proximal tubules of the same nephron and a decrease in absolute proximal reabsorption. Microperfused inulin was retained in the tubule suggesting this finding reflected a true reduction in SNGFR. Concurrent infusion of high dose furosemide (2 x 10(-4)M) and bumetanide (2 x 10( 5) M), but not low dose furosemide (2 x 10(-5) M), prevented the UN induced reduction in SNGFR. High dose furosemide begun after UN perfusion also prevented reduction in SNGFR. Continuous direct measurement of glomerular capillary hydrostatic pressure revealed no change. Distal intratubular Na+ and Cl- concentration increased significantly after UN perfusion. Activation of tubuloglomerular feedback mechanisms best explains the reduction in glomerular ultrafiltration that is characteristic of nephrotoxic forms of tubular injury. PMID- 2601255 TI - Glomerular and proximal tubular morphology after single nephron obstruction. AB - This study examined the effect of blocking proximal tubule lumens on glomerular and early proximal tubular morphology. Single nephrons in the rat kidney were blocked with wax by micropuncture. After one day, one week, or one month of obstruction, the kidneys were fixed with glutaraldehyde by intravascular perfusion, and nephron structure was examined by light and electron microscopy. Following obstruction, glomerular changes developed more slowly than tubular changes. After one day, the only change noted in some glomeruli was the presence of inflammatory cells. The only tubule change upstream to the block was a focal loss of apical microvilli. This is in contrast to the severe damage previously reported (Evan, Tanner: Kidney Int 30: 818-827, 1986) in downstream proximal tubule segments at this time. After one month of obstruction, glomerular size was decreased and the glomerular filtration membrane was abnormal. Tubular cell size was decreased, apical microvilli were lost, basolateral interdigitations were reduced, and mitochondria were fewer and abnormally oriented. Interstitial fibrosis was present. Changes in nephron structure develop slowly after obstruction, perhaps because continued filtration and reabsorption maintain nephron integrity. Eventually, blocked nephrons atrophy, probably because of reduced blood flow, disuse, and inflammatory responses. PMID- 2601256 TI - Effects of deferoxamine, feroxamine and iron on experimental mucormycosis (zygomycosis). AB - Mucormycosis was induced in healthy guinea pigs by the i.v. injection of spores from Rhizopus microsporus var. rhizopodiformis or from Rhizopus oryzae, leading to a reproducible mortality. Pretreatment with one dose of 50 mg of deferoxamine (DFO) shortened animal survival from 4.2 +/- 0.4 to 3.3 +/- 0.5 days for Rh. rhizopodiformis and from 8.8 +/- 0.4 to 7.3 +/- 1.9 days for Rh. oryzae (P less than 0.05). Survival was shortened even more after 4 doses of DFO (P = 0.0013 for Rh. rhizopodiformis and P = 0.002 for Rh. oryzae). After Rh. oryzae infection, animal survival decreased similarly after DFO, feroxamine or DFO combined with Fe3+ citrate (P less than 0.001). Fe3+ citrate also decreased survival (P = 0.0011), although significantly less than DFO either alone or combined with Fe3+. In vitro growth of both fungal strains was enhanced by addition of either DFO or Fe3+ at 0.001 to 1 mmol in the medium. DFO abolished the prolonged survival induced by amphotericin B in vivo and in vitro. Indeed, four doses of DFO abolished the improved survival due to amphotericin B (P = 0.0019 for Rh. rhizopodiformis and P = 0.002 for Rh. oryzae); DFO combined with Fe3+ at greater than or equal to 0.1 mmol decreased the antifungal activity of amphotericin B in vitro. These results point to a major role of DFO in the pathogenesis of mucormycosis in dialysis patients and suggest that DFO behaves as a siderophore for Rhizopus strains, stimulating their growth. PMID- 2601257 TI - Acute cyclosporine renal dysfunction reversed by dopamine infusion in healthy subjects. AB - Up to now, no studies have been performed in normal humans to investigate the role of renal hemodynamic abnormalities in relation to acute-cyclosporin A (CsA) renal dysfunction and to verify whether the specific renal vasodilator, dopamine, can counteract these abnormalities. Eight normal subjects were examined both (A) after oral CsA (12 mg/kg body wt) and (B) after oral CsA + dopamine infusion (2 mg/kg body wt/min), under water diuresis. Both in protocols A and in B, four basal renal clearances were performed before CsA and every twenty minutes for four hours after CsA administration. In protocol A, after CsA, inulin (GFR) and PAH clearance (RPF) fell by up to 27% and to 41%, respectively, so that filtration fraction (FF) increased (P less than 0.01). A slight (not significant) hypertension occurred while renal resistances were markedly raised (P less than 0.001). Fractional urine and Na+ excretion as well as CH2O decreased, while UOsm increased (P less than 0.01). In protocol B, dopamine was infused from 120 to 180 minutes after CsA (that is, when the maximal adverse effects of CsA on renal hemodynamics had been observed in A). Dopamine infusion could reverse completely the effects of CsA on RPF, GFR, fractional urine output and CH2O; only UOsm remained higher than normal in conclusion with an increased fractional excretion of sodium (P less than 0.01). No changes were observed in plasma renin activity, aldosterone and in urinary epinephrine and norepinephrine excretion both in protocols.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601258 TI - Direct inhibitory effect of calcitriol on parathyroid function (sigmoidal curve) in dialysis. AB - The effect of intravenous calcitriol on parathyroid function was evaluated in nine chronic hemodialysis patients with secondary hyperparathyroidism. Two micrograms of calcitriol were administered intravenously after dialysis thrice weekly for ten weeks. Parathyroid function was assessed by inducing hypo- and hypercalcemia with low calcium (1.0 mEq/liter) and high calcium (4.0 mEq/liter) dialyses before and after ten weeks of intravenous calcitriol therapy. To avoid hypercalcemia during calcitriol administration, the dialysate calcium was reduced to 2.5 mEq/liter. Parathyroid hormone (PTH) values (pg/ml) from dialysis-induced hypo- and hypercalcemia were plotted against serum ionized calcium, and the sigmoidal relationship between PTH and calcium was evaluated. Basal PTH levels fell from 902 +/- 126 pg/ml to 466 +/- 152 pg/ml (P less than 0.01) after therapy without a significant change in the serum total calcium concentration. The ionized calcium-PTH sigmoidal curve shifted to the left and downward after calcitriol therapy. The maximal PTH response during hypocalcemia decreased after calcitriol from 1661 +/- 485 pg/ml before calcitriol to 1031 +/- 280 pg/ml afterward (P less than 0.05). The PTH level at maximal inhibition due to hypercalcemia decreased from 281 +/- 76 pg/ml before calcitriol to 192 +/- 48 pg/ml afterward (P less than 0.05). The slope of the sigmoidal curve changed from -2125 +/- 487 to -1563 +/- 385 (P less than 0.05). The set point of ionized calcium (4.60 +/- .11 mg/dl before vs. 4.44 +/- .07 mg/dl after) did not change significantly with calcitriol therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601259 TI - Kinetics and efficacy of deferoxamine in iron-overloaded hemodialysis patients. AB - We evaluated the kinetics and efficacy of deferoxamine (DFO) therapy in iron overloaded hemodialysis patients. Concentrations of DFO and its chelated product, feroxamine (Fx), were assessed following single-dose DFO administration in twelve patients, and during chronic therapy over one year's time in eight, similarly iron-overloaded dialysis patients. A functional assay which relies on measurements of iron and iron binding capacity for the determination of Fx and DFO, respectively, was corroborated with liquid chromatographic techniques. Half life measurements were also corroborated with tracer doses of 14C-DFO and 59Fe feroxamine. Intradialytic DFO half-life (2.3 +/- 1.1 h) was considerably less than interdialytic half-life (26 +/- 1 hr). Unbound DFO was found to persist throughout the interdialytic period. Calculation of the percent saturation of the DFO dose indicated that only 30% of a given dose is chelated. The amount of iron removed dialytically was approximately 13.1 +/- 2.7 mg per dialysis session. Chronic DFO administration was also shown to enhance gastrointestinal iron excretion threefold. However, ferritin levels decreased by only 25% after one year of thrice-weekly DFO therapy. We conclude that DFO therapy for iron overloaded hemodialysis patients is optimized by its administration interdialytically, and results in slow removal of iron, via both dialytic and gastrointestinal routes. PMID- 2601261 TI - Abstracts. Australasian Society of Nephrology, twenty-fifth annual scientific meeting. February 26-March 1, 1989, Newcastle, New South Wales, Australia. PMID- 2601262 TI - Abstracts. Korean Society of Nephrology, 8th annual scientific meeting. June 10 11, 1988, Seoul, Korea. PMID- 2601260 TI - Risk factors in idiopathic renal vasculitis and glomerulonephritis. AB - In this retrospective study, we analyzed clinical laboratory, and pathologic variables to determine their value in predicting survival and survival free of renal failure for 170 consecutive patients with idiopathic renal vasculitis and glomerulonephritis evaluated during a 15 year period. Of the 170 patients, 108 had focal segmental necrotizing glomerulonephritis alone (FSNGN), 33 had FSNGN and small-artery vasculitis, and 29 had FSNGN and medium-sized artery vasculitis. Considerable overlap of clinical, laboratory, and pathologic findings existed among the three groups. Overall patient survival was 81% at one year, 61% at five years, and 44% at ten years, significantly less than expected survival. Overall survival free of renal failure, by definition, was lower than patient survival. There were no differences among these three groups in patient survival or survival free of renal failure. Multivariate analysis identified leukocytosis and serum creatinine level as independent predictors of patient survival and survival free of renal failure. In addition, univariate analysis identified age and hypertension as significant risk factors but did not add independent predictive value for these two end points. In patients with serum creatinine levels less than 4 mg/dl, the effect of increasing levels of leukocyte count was significantly associated with poorer outcomes for both patient survival (P = 0.006) and survival free of renal failure (P = 0.024). Outcomes for these two end points were worse for patients with lower serum creatinine levels (less than 4.0 mg/dl) and high leukocyte counts (greater than 16,000/mm3) than for those with serum creatinine levels greater than or equal to 4.0 mg/dl. PMID- 2601263 TI - Symposium on signal transduction. PMID- 2601264 TI - Retinoic acid affects the cell cycle and increases total protein content in epithelial cells. AB - Retinoids and particularly retinoic acid (RA) have been incriminated in the adaptation to uninephrectomy and compensatory kidney growth in humans. However, there is no data assessing the effects of RA on renal cells. Since the bulk of the compensatory kidney growth is due to tubular cells, we studied the effects of RA, retinol and epidermal growth factor (EGF) on a rabbit kidney epithelial cell line RK13 in culture. RA significantly increased thymidine incorporation by 42 +/ 8% (P less than 0.01). This increase appeared as soon as three hours after adding RA and could still be observed after five days. Total protein content was also increased by RA by 37 +/- 4% (P less than 0.01). Flow cytometer analysis showed a significant decrease in the percentage of resting cells (G0-G1 phases) induced by RA (-9.4 +/- 2%; P less than 0.01). We observed similar results in growth factor free medium, and the RA induced changes were the same in confluent and non-confluent cells. Retinol did not modify thymidine incorporation or total protein content. EGF increased by 75% thymidine incorporation (P less than 0.01). In serum free conditions RA failed to have a synergistic effect with EGF. These data show that RA is able to induce modifications in kidney epithelial cells compatible with those observed in hypertrophy while retinol is not. These modifications are not due to other growth factor potentiation but to RA itself, and are independent of the contact-inhibition phenomenon. PMID- 2601265 TI - Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate. AB - Clinical and experimental studies have shown that citrate markedly enhances the intestinal absorption of aluminum (Al), but the site and mechanism of enhanced absorption are unknown. To determine where in the gastrointestinal tract aluminum citrate (Alcitr) was absorbed. Alcitr was gavaged with D-[1-3H] glucose in male Sprague-Dawley rats. Plasma Al levels increased rapidly and simultaneously peaked with D-[1-3G] glucose, suggesting early proximal bowel absorption. In in vitro duodenal and jejunal everted gut preparations, Alcitr incubation resulted in increased tissue Al levels and markedly enhanced transmural transport of Al and citr. Unlike citr, the transmural movement of Al was independent of temperature (37 degrees C vs. 4 degrees C). On the other hand, Al lactate (al Lac) increased tissue associated Al levels but had no effect on transmural Al movement. To determine if this large flux of Al following Alcitr administration was due to paracellular movement, ruthenium red and Ussing chamber studies were used to evaluate the morphologic and functional integrity of cellular tight junctions. Alcitr, as opposed to AlCl3, markedly increased ruthenium red deposits in intercellular spaces, especially around goblet cells, and induced a prolonged significant reduction in transmural resistance. Alcitr also resulted in rapid and nearly complete (99.7%) chelation of free calcium, an event known to disrupt cellular tight junction integrity. Taken together, these data suggest that enhanced Al absorption following administration of Alcitr occurs in the proximal bowel via the paracellular pathway due to the opening of cellular tight junctions. PMID- 2601266 TI - Mechanism of action of angiotensin II on isolated rat glomeruli. AB - Angiotensin II (Ang II) regulates glomerular filtration rate by contracting mesangial cells and thereby decreasing glomerular filtration surface area. To elucidate the cellular mechanism of this action, we investigated the roles of Ca and protein kinase C (PKC) activation in Ang II-induced glomerular capillary vasoconstriction using 3H-inulin to measure the extracellular (largely intracapillary) volume of isolated decapsulated rat glomeruli. Ang II (1 microM) rapidly decreased the glomerular inulin space (GIS), bringing about a maximal decrease at five minutes, which lasted up to 30 minutes. When incubated in 0.5 mM EGTA-containing Ca-free medium or in the presence of 1 microM diltiazem or verapamil, the sustained phase (after 7 min) was completely inhibited. The initial effect (at 3 and 5 min) was only partially inhibited by these maneuvers but was completely inhibited by trifluoperazine or W-7, which indicated that it was dependent on calmodulin and, accordingly, on Ca probably released from the intracellular store. The sustained effect was mimicked by 12-0 tetradecanoylphorbol-13-acetate (TPA) in the presence of extracellular Ca, but was not in its absence. The sustained effect was also inhibited by H-7, an inhibitor of PKC, and by W-7, which indicated that PKC activation and influx of extracellular Ca are both important. Combined treatment with A23187 and TPA could mimic both the initial and sustained effect of Ang II in the presence of extracellular Ca, though either one of them failed to do so when used alone. These results suggest that the initial effect of Ang II on GIS is mediated by Ca released from the intracellular store, on the one hand, and the sustained effect by extracellular Ca influx and PKC activation, on the other. PMID- 2601267 TI - [40 years of East Germany--reflections on pediatric and adolescent medicine with respect to the future]. PMID- 2601268 TI - [Diagnosis of mucoviscidosis by examination of sweat: value of conductometry]. AB - Two methods for the determination of sodium in the sweat after stimulation by pilocarpine-iontophoresis were compared in 227 patients, among them 27 with a known cystic fibrosis. These two methods were 1. the standardized method by flame fotometry (State Pharmacopoeia of the German Democratic Republic) and 2. the determination of the sweat conductance by the new apparatus "CF-Conductognost". Both methods showed a good correlation. We recommend the conductometry for the decentralized screening because it saves time and gives results immediately. But in all patients with a questionable or pathologic value of conductance the sweat test should be repeated with the standardized method. This concerns only about 10 per cent of all patients. PMID- 2601269 TI - [Quantitative-morphometric characterization of the lung structure in congenital heart defects exemplified by Fallot disease and isolated ventricular septal defect]. AB - The aim of this study was to investigate the possibility of determination of lung changes in congenital deformity of heart and vessels by the method of Weibel and Elias (1967) for count of points in the lung (volume of alveoli and interstitium). The results show that this method is suitable for the estimation of quantitative changes in Morbus Fallot. In order to decide the degree of arteriosclerosis an additional measurement of the wall thickness of lung vessels is necessary in cases of ventricular septal defect. The arteriosclerosis is an important factor for the secondary variations, especially of the right heart. A field of application of this method could be the praeoperative lung biopsy for the clarification of the question of operability. PMID- 2601270 TI - [Rubella virus infection as a cause of nephrosis in infancy]. AB - There is obtained the rare disease of the nephrotic syndrome in an infant during the first year of life. The diagnosis of symptomatic nephrosis in the course of an infection with Rubellavirus was postulated on the basis of clinical and serological results. The heterogenous signs of the nephrosis in the first year of life, the possible causes, the treatment and the prognosis are discussed. PMID- 2601271 TI - [Mucoviscidosis and marathon running. Evaluation of physical endurance in patients with cystic fibrosis]. AB - The authors give a survey on the problems of sport activities in CF patients, which is based on own experience and the data of the literature. All these patients should take part in endurance sport. The regular training program should be carefully planned according to the state of each single patient. Regular medical supervision of it is necessary. Only in selected cases CF patients, too, can take part in marathon races. PMID- 2601272 TI - [Risk factors in the susceptibility for infection in young children]. AB - The frequency and the duration of acute respiratory disease (ARD) have been registered in 245 children aged from 6 to 36 months staying in 8 creches of a large town during a period of one year. The exterior conditions of life were comprehended. From this material 10 risk factors were determined. By elaborating a score for prognosis it was possible to discriminate 2 groups of children. One part was susceptible, the other resistant to infections. This publication should be a contribution for answering the question for creche fitness after getting over an ARD. PMID- 2601273 TI - [Aqueous humor outflow pathways following trabeculectomy in patients with glaucoma]. AB - The distribution pattern of fluorescein sodium after trabeculectomy was studied in 43 patients. There was good correlation between the formation of a visible filtering bleb and fluorescein accumulation at the trabeculectomy site. The mechanism of action of trabeculectomy is discussed with regard to alternative outflow pathways. PMID- 2601274 TI - [Oculo-oscillodynamography findings in glaucoma without hypertension]. AB - Oculo-oscillodynamography after Ulrich was performed in 27 patients suffering from glaucoma without hypertension (so-called low-tension glaucoma). Patients who had severe systemic disease or were receiving systemic medication which might influence IOP, and patients with narrow angle and an IOP higher than 22 mm Hg were excluded. In 85% of the patients a severe decrease in systolic ciliary perfusion pressure was found, whereas the systolic retinal and diastolic ocular perfusion pressures were significantly lower in almost 30% of the cases. Glaucoma without hypertension appears to be caused by the vascular change at the disk. PMID- 2601275 TI - [Measuring the optic papilla with planimetry and the optic nerve head analyzer in glaucoma and suspected glaucoma. I. Comparison of the 2 measuring methods]. AB - Two-dimensional planimetric measurement of the neuroretinal rim using the method described by Betz has proved to be one of the most objective parameters in evaluating the optic nerve head. Using a three-dimensional stereoscopic measuring procedure (ONHA) described by Cornsweet, the volume of the papillary excavation can be quantified. The two methods were compared in a study involving 67 eyes with confirmed and suspected glaucoma. In agreement with published data, the correlation between the two measuring procedures was good as regards the disk surface (r2 = 0.73), the surface of the excavation (r2 = 0.90), and the cup/disk ratio (r2 = 0.63), although the last-mentioned parameter is calculated differently. While the disk surface as measured by planimetry was significantly greater than with ONHA, the cup surface measurements were almost exactly the same. In contrast to the results of other authors, the measurements of the neuroretinal rim surface correlated poorly (r2 = 0.09). The difference between the two methods in measuring the rim surfaces depends to a great extent on their absolute size and on the cup surface. The different procedures for defining the boundary of the excavation (in planimetry horizontal boundary definition, with the ONHA 150 micrometers below the retinal surface) are considered responsible for this. Advantages and drawbacks of these two clinical measuring methods are discussed. Once the currently excessive variability in the measurements has been reduced, measurement of the excavation volume could prove to be an important parameter for assessing the development of the optic nerve head in confirmed or suspected glaucoma cases. PMID- 2601277 TI - [Graphic analysis of topographic trends in perimetry follow-up of glaucoma]. AB - GATT is a new, graphic method of showing the development of visual fields in glaucoma and other diseases. The grayscale maps of a series of two or four fields are superimposed with a simple logic, producing the following pattern: all stable areas are displayed in the usual way, thus giving defects a typical appearance. Changed areas appear as stripes, alternately showing the grayscale of the two fields. The orientation of the stripes is vertical in zones of improvement and horizontal in areas of deterioration. The level of contrast indicates the amount of change. The authors examined the development of the visual fields in 30 glaucomatous eyes. With the help of GATT it was established that areas of change were close to existing defects. Second, most of the changes were at the periphery. GATT is not only proving to be a method for perimetric follow-up in glaucoma cases that furnishes much useful information, but is also raising hopes of new findings concerning the course of glaucoma. PMID- 2601276 TI - [The retinal nerve fiber layer in normal and glaucomatous eyes. II. Correlations]. AB - The retinal nerve fiber layer is different in normal and glaucomatous eyes. We correlated semi-quantitative data of the retinal nerve fiber layer of 398 eyes with chronic primary open-angle glaucoma and of 234 normal eyes with the intra- and parapapillary morphometric signs and with the perimetric indices. The three parameters "sequence of the fundus sectors concerning the best visibility of the retinal nerve fiber bundles", "visibility of the nerve fiber bundles", and "localized defects" were significantly (p less than 0.001) correlated to 1) area of the neuroretinal rim as a whole and in four different optic disc sectors, 2) neuroretinal rim width determined every 30 degrees, 3) optic cup area, diameters and form, 4) horizontal and vertical cup/disc ratios and the quotient of the horizontal to vertical cup/disc ratio, 5) area and width of zone "Alpha", zone "Beta", and the total parapapillary chorio-retinal atrophy, 6) diameter of the retinal vessels, 7) grade of a "tesselated fundus", and 8) the visual field loss. If only the inferior temporal and the superior temporal sectors were considered, the retinal nerve fiber bundles were less visible in that sector with the largest notch in the neuroretinal rim, the smaller neuroretinal rim area and width, the thinner retinal vessels, and the larger zone "Alpha", zone "Beta", and total parapapillary chorio-retinal atrophy. The glaucomatous changes in the retinal nerve fiber layer are correlated in time and location with the intra- and parapapillary and the perimetric alterations. Evaluation of the retinal nerve fiber layer is a useful method to detect a glaucomatous optic nerve damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601278 TI - [Gonioscopy of the shallow anterior chamber]. AB - During gonioscopy the aqueous humor can be shifted by appropriate indentation with the goniolens (Forbes test). The iris root is affected in a variety of ways: it may sink in, troughlike, or be deformed to an S-shape, or remain unchanged. The different findings depend on the configuration of the ciliary processes and the position of the lens equator; they enable conclusions to be drawn concerning the risks of inverse reaction to miotics or of ciliary lens block (malignant) glaucoma. PMID- 2601279 TI - [Progress in early detection and follow up of glaucoma]. AB - The importance of Hans Goldmann's contributions to clinical tonometry is discussed in detail. One example is the principle of an applanation diameter of 3.06 mm, which was established by him and is still the basis for the various methods of clinical tonometry today. Therefore, further advances in this field can only be concerned with facilitating the application of this principle. An instrument which can be used by both physician and patient is described. By facilitating more frequent tonometric examinations it would ensure much better glaucoma control than is at present possible. A further application of a self test tonometer of this kind, which is not affected by gravity, is space medicine. It is planned to use the instrument in the German Spacelab D2 mission in 1991. PMID- 2601280 TI - [Long-term course of 6 boys with congenital nephrogenic diabetes insipidus]. AB - From 1975-1986 6 boys with congenital nephrogenic diabetes insipidus were diagnosed at the age of 3 months to 10 years. Symptoms appeared within the first few weeks of life. The diagnosis was confirmed by polyuria, low urinary osmolality (97-225 mosm/kg H20), hypernatraemia (max. 171 mmol/l) and the missing response to vasopressin. The treatment was variable; 4 boys received only hydrochlorothiazide (2-2.5 mg/kg/d) which lead to a reduction of the daily urinary volume of 26-44%. Hyperelectrolytaemia disappeared and a normal thriving could be achieved. Later an additional treatment with indomethacin (2 mg/kg/d) was necessary in 3 boys because of an increase of polyuria; there was a further reduction of the daily urinary volume of 50-60%. The combination of hydrochlorothiazide and indomethacin in the treatment of the congenital nephrogenic diabetes insipidus was well tolerated and seems to be--especially during the first few years of life--a necessary and effective treatment which allows a normal thriving and psychointellectual development. PMID- 2601281 TI - [Juvenile form of tyrosinemia type I]. AB - A 1-3/12-year-old Turkish boy born of consanguineous parents was hospitalized in poor general condition with disorientation, hepatosplenomegaly, and rickets. Laboratory tests showed pronounced symptoms of hepatic dysfunction, rickets, and Fanconi's syndrome with acidosis. The diagnosis juvenile type I tyrosinemia was based on the anamnesis, hepatorenal symptoms, and elevated tyrosine and methionine blood levels as well as the pathognomic findings of heavy succinylacetonuria and absent fumarylacetoacetase activity in the fibroblasts. Etiology, pathobiochemistry, clinical symptoms, differential diagnosis, and therapy of this rare autosomal-recessive inherited metabolic disease were discussed. PMID- 2601282 TI - [Pulmonary sequestration in infants: diagnosis and therapy exemplified by a newborn infant]. AB - Infants with intra- or extralobular lung-sequestrations normally suffer from chronic infections. In our case an infant is described who had a triangular area in chest X-rays behind the heart. Lung scintigraphy and computer-tomography could not commit the diagnosis. Only invasive angiography showed the sequestration. Although without symptoms the baby was operated preventively. Postoperative course was without complications. PMID- 2601283 TI - [Nursing care of aged (IV). Disturbances of ego integrity in elderly people, strategy and nurse's role]. PMID- 2601284 TI - [Nursing research trends on powerlessness]. PMID- 2601285 TI - [Powerlessness: assessment and nursing diagnosis]. PMID- 2601287 TI - [Report after visiting institutions of home health care in the U.S.A]. PMID- 2601286 TI - [Powerlessness in acute and chronically ill patients: nursing strategies]. PMID- 2601288 TI - [Managing nutritional problems in advanced cancer]. PMID- 2601289 TI - [An analysis of factors of quality nursing care]. PMID- 2601290 TI - [Nursing care of aged (IV). Psychological processes of aging]. PMID- 2601292 TI - [Prevention of decubitus ulcers and their treatment]. PMID- 2601291 TI - [Evaluation study on the nursing student's clinical experience in care of the patient during hospitalization and after discharge]. PMID- 2601293 TI - [Problem decubitus ulcer. The solution is an ideally humid environment]. PMID- 2601294 TI - [Nursing in the neurologic area]. PMID- 2601295 TI - [Nosocomial pneumonias and prevention of pneumonia]. PMID- 2601297 TI - [Probable situation of nursing in the 90s. The need for nursing personnel]. PMID- 2601296 TI - [Current therapeutic aspects in arterial and venous vascular occlusion]. PMID- 2601298 TI - [Pathophysiology of decubitus ulcers and their prevention]. PMID- 2601299 TI - Glomerular epithelial detachment, not reduced charge density, correlates with proteinuria in adriamycin and puromycin nephrosis. AB - To identify the structural change coincident with increased glomerular permeability in both adriamycin (ADR) and puromycin-aminonucleoside (PAN) nephrosis, we explored the temporal correlation between developing proteinuria, the reduction in glomerular polyanions, and the detachment of epithelium from glomerular basement membrane (GBM). Sprague-Dawley rats received a single tail vein injection of PAN (150 mg/kg), ADR (7.5 mg/kg) or saline. Nephrotic-range proteinuria appeared between days 2 to 5 in the PAN-treated and days 5 to 10 in the ADR-treated rats. The GBM heparan sulfate charge density and epithelial membrane sialic acid (SA) content were determined before, during and after the rise in proteinuria. Polyethyleneimine was used to detect heparan sulfate and the number staining of renal cortical slices was used to detect heparin sulfate and the number of sites/microns GBM in the lamina rara externa were counted on electron micrographs (magnification x60,000). Controls had a regular distribution of polyethyleneimine 20.19 +/- 1.72 sites/microns (X + SD). In ADR rats, the polyethyleneimine density decreased by day 5, 18.61 +/- 1.79 sites/microns (p less than 0.05) which persisted to day 15, 17.38 +/- 1.27 sites/microns (p less than 0.02). PAN rats, by day 1, had significant reduction, 14.94 +/- 1.47 sites/microns (p less than 0.05), which persisted to day 20. The total membrane bound SA content of isolated glomeruli was analyzed with a modified Warren's method. The SA content in control glomeruli was 46.8 +/- 8.0 nmol/mg glomerular protein (X +/- SD). In ADR rats, there was significant decrease in SA content to 84 +/- 3% of control (p less than 0.01) at day 15. In PAN rats, by day 2, the SA content was decreased to 73 +/- 18% of control (p less than 0.05). In both models, scanning and transmission electron microscopy revealed epithelial foot process fusion, loss of slit diaphragms, and vacuolization before increased proteinuria. Epithelial detachment from the GBM and rupture of vacuoles occurred coincidently with rapid development of nephrotic proteinuria in both models. In summary, reduced GBM heparan sulfate and epithelial SA content do not correlate with the onset of altered glomerular permeability, whereas epithelial detachment is coincident with the development of massive proteinuria in both ADR and PAN nephrosis. PMID- 2601300 TI - Ultrastructure of monkey peripheral blood basophils stimulated to develop in vivo by recombinant human interleukin 3. AB - Ultrastructural and cytochemical studies of peripheral blood samples from a monkey continuously infused with recombinant human interleukin 3 were performed. Recombinant human interleukin 3 stimulated a delayed granulocytosis primarily characterized by numerous mature basophils and fewer eosinophils and neutrophils. Basophilic leukocytes were identified by ultrastructural analysis. They were found to be typical granulocytes with polylobed nuclei containing condensed chromatin and numerous cytoplasmic granules. Basophil secretory granules were filled with homogeneous dense contents and were larger than eosinophil and neutrophil secretory granules. Evidence of increased basophil production was accompanied by interleukin 3-associated activation morphologies. These included increased numbers of cytoplasmic and granule-associated vesicles, as are routinely present in a non-IgE-mediated basophil release reaction, termed piecemeal degranulation, and focal perigranular matrix swelling and granule membrane fusion which accompanies anaphylactic degranulation of basophils in other species. Monkey basophils were shown to have a different ultrastructural morphology than that published for monkey mast cells, but exhibited general morphologic criteria for the identification of circulating mature basophils in a number of species. Like human and guinea pig basophils, monkey basophils did not display endogenous peroxidase or peroxidatic activity in a cytochemical assay which simultaneously identified peroxidase-positive granules in neutrophils and eosinophils as well as in synthetic structures in eosinophils. In summary, these studies have identified monkey basophils in an in vivo recombinant human interleukin 3-stimulated model. Interleukin-3 induction of basophilia clearly allowed differentiation of activated mature basophils from eosinophils and neutrophils and mast cells in this species using ultrastructural morphologic criteria. PMID- 2601301 TI - Immunoelectron microscopic identification of human AA-type amyloid: exploration of various monoclonal AA-antibodies, methods of fixation, embedding and of other parameters for the protein-A gold method. AB - Using the postembedding protein-A gold technique ten monoclonal antibodies directed against amyloid-A protein (AA) were examined by immunoelectron microscopy to identify amyloid-A (AA) amyloid fibrils in plastic-embedded renal tissue of five patients and two controls. Two monoclonal antibodies (mc1, mc20) specifically labeled these amyloid deposits; two additional ones (mc4, mc13) bound with an intermediate rabbit anti-mouse IgG antiserum. These monoclonal anti AA antibodies clearly separate amyloid fibrils from morphologically similar fibrils in the vicinity. Employing varying embedding media, fixation techniques, as well as etching and staining protocols, we adapted this method for the immunoelectron microscopic identification of AA-type amyloid fibrils and for the antigenic diagnosis of AA-type amyloid on routinely processed ultrathin sections. PMID- 2601302 TI - The effects of emphasis on passage comprehension. AB - It may be inferred from reaction time studies that the location of emphasis on nouns and noun phrases facilitates their comprehension (understanding and memory). However, we know of no previous demonstration of improved passage comprehension in normal listeners associated with emphasis placement. The present experiment examined effects of emphasis on comprehension of 12 passages that were read aloud and tape recorded. Emphasis placement was varied by splicing sentences containing emphasized or nonemphasized noun phrases into passages without altering the wording of the passages. These passages, contrasting in emphasis, were presented to 60 listeners. Comprehension was measured with multiple-choice, recognition questions that required subjects to link ideas across sentences. Comprehension was accurate significantly more often when correct response alternatives had been emphasized (71%), than when incorrect alternatives had been emphasized (56%), or no emphasis occurred in passages (57%). Findings reflect enhanced comprehension of emphasized items in terms of their meaning links to other concepts presented in passages. Results support the pragmatic assumption that the role of emphasis is to delineate constituents important in discourse meaning. PMID- 2601303 TI - A familial study of severe phonological disorders. AB - The present study examined the familial basis for severe phonological disorders. Twenty children with severe phonological disorders and their siblings were compared to 20 normally developing children and their siblings on measures of phonology, language, reading, and motor ability. Results revealed that the siblings of the disordered children performed more poorly than control siblings on phonology and reading measures. Disordered subjects' phonological skills correlated significantly and positively with their siblings', whereas controls' scores did not. Families of disordered children reported significantly more members with speech and language disorders and dyslexia than did families of controls. Sex differences were reflected in the incidence but not the severity or type of disorder present. These findings suggest a familial basis for at least some forms of severe phonological disorders. PMID- 2601304 TI - Visual evoked potentials: relation to adult speechreading and cognitive function. AB - This study investigated the putative relationship between visual evoked potentials (VEPs) and specific aspects of speechreading. The nature and constraints of the relationship between VEPs and cognitive functioning was also examined. The original finding of Shepherd, DeLavergne, Frueh, and Clobridge (1977) that visual-neural speed (VN 130) predicts speechreading skill was not replicated. However, the picture is rather complex in that we find significant correlations for some context-free word discrimination and sign-alphabet testing conditions. These correlations occur only for the VN 130/P 200 peak-to-peak amplitude measure, not for neural speed. Nevertheless, visual-neural speed (VN 130 and P 200) was relevant to certain aspects of long-term memory access (i.e., letter matching, Posner & Mitchell, 1967) and to complex short-term memory function (i.e., reading span, Baddeley, Logie, Nimmo-Smith, & Brereton, 1985). PMID- 2601305 TI - Palatometric specification of stop, affricate, and sibilant sounds. AB - This investigation used palatometry to study stops, sibilants, and affricates in CV syllables (C = t,d,k,g,tf,d3; V = i,a) spoken by nine normal 6- to 14-year-old children. The measures focused on place, manner, timing, and area of linguapalatal contact. Similarities and differences between the sound classes, actions across segments of the articulatory gestures, and age effects were identified and described. The affricates were observed to have stop and sibilant portions demarcated by a partial plateau in the linguapalatal contact releasing gesture. The sibilant portion was formed in the same place and with the same groove dimensions as /f,3/. The older subjects reached initial articulatory positions faster, produced the consonant sounds more quickly, generated vowels with shorter durations, and articulated more posteriorly than did younger ones. PMID- 2601306 TI - Electrical activity from the superior pharyngeal constrictor during reflexive and nonreflexive tasks. AB - The purpose of this investigation was to determine, in a quantitative manner, which, if any, nonswallowing tasks produce significant levels of activation in the superior pharyngeal constrictor muscle of normal human subjects. Bipolar hooked wire electrodes were inserted in the superior pharyngeal constrictor muscle of 15 healthy subjects. Electrode placement was controlled. Each subject performed two reflexive tasks, six voluntary tasks requiring phonation, and four nonspeech voluntary tasks. The electromyogram (EMG) was rectified and integrated. The resulting number was then transformed by taking its natural logarithm. An ANOVA was performed and a linear model was estimated. The magnitude of the EMG activity was related to the location of the electrodes. The largest values were recorded in the lateral-superior placement, followed by the lateral-inferior, medial-inferior and medial-superior. The superior pharyngeal contrictor was found to be a muscle activated primarily during reflexive activity. There was a general trend in the amplitude of EMG activity in relationship to task. Swallowing produced the greatest amount of activity and a gag produced about 60% of the activity produced by the swallow. Two tasks, production of the work /hok/ in which the phoneme /k/ was stressed, and a "modified Valsalva," which was actually a hard /k/ held for several seconds, produced the next greatest level of EMG. PMID- 2601307 TI - Analysis of language-speech samples with salt and pepper. AB - Microcomputer-aided analysis of spontaneous language-speech samples offers researchers an efficient means of analyzing large amounts of data. It may be necessary, however, to format samples for more than one software program in order to obtain comprehensive morpho-syntactic and phonetic/phonologic analyses. This paper suggests a procedure for the combined use of SALT (Systematic Analysis of Language Transcripts, Miller & Chapman, 1985) and PEPPER (Programs to Examine Phonetic and Phonologic Evaluation Records, Shriberg, 1986) that is designed to minimize the duplication of effort involved in following two different formatting procedures. Results of a study undertaken to explore methodological issues in the combined use of SALT and PEPPER generally support the validity, reliability, and efficiency of the procedure. Results also raise some issues concerning the use of narrow phonetic transcription as opposed to standard orthographic transcription of continuous language-speech samples. PMID- 2601308 TI - The bifrequency binaural interaction component of the auditory brainstem response. AB - The binaural interaction component of the auditory brainstem response was investigated in three stimulus conditions, 1000-Hz tone pips to both ears, 3000 Hz tone pips to both ears, and 1000-Hz tone pips to the left ear and 3000-Hz tone pips to the right ear. A binaural interaction component was produced in all conditions in which the stimuli were presented in quiet and in broadband noise, suggesting that a frequency separation of 2000 Hz between ears can produce a fused image. Responses to the bifrequency stimuli in noise indicated the peak A of the binaural interaction component is not dependent solely on the slope of wave V because when the noise caused a dissociated binaural wave V, peak A was associated only with the trailing wave V. PMID- 2601310 TI - On the nature of phonological development: evidence from normal children's spelling errors. AB - Spelling errors of 45 elementary school children were analyzed for phonological process patterns. A considerable proportion of errors involved both syllabic reduction and feature changes similar to those seen in normal speech development. Results are discussed with respect to application of phonological constructs to the study of development of speech production. An alternative psychological model of development is proposed in outline. PMID- 2601309 TI - Language skills of children with different preschool experiences. AB - This study examined the language at age 5 of socioeconomically disadvantaged children who had been randomly assigned at birth to a language-enriched day care program with a parent education component, a parent education program without a language-enriched day care, or no treatment. The interventions were administered between the ages of 3 months to 5 years. Language measures, reflecting children's ability to manipulate topics, as well as their structural complexity, semantic diversity, and general talkativeness were examined. The results showed that the disadvantaged children who attended the language-enriched day care program with the parent education component used a significantly greater proportion of high quality topic manipulation skills and less low quality topic manipulation skills during conversation than did children in the other two groups. The day care effect on high quality topic manipulation was present even after adjusting for children's intelligence and for the amount of community day care experience of the children in the parent education alone and control groups. No significant treatment differences were found for structural, semantic, and talkativeness measures. Implications of the result for early language intervention are discussed. PMID- 2601311 TI - Perception/production relationships in the development of the vowel duration cue to final consonant voicing. AB - The purposes of this study were to assess: (a) the development of identification in children for the vowel duration cue to final consonant voicing and (b) the perception/production relationships in children for the vowel duration cue to final consonant voicing. Subjects were 30 children divided equally into three age groups, and 10 adults. Productions consisted of 15 repetitions of two target syllables (beet, bead) analyzed acoustically for vowel duration. From these were calculated category boundary, category separation, and variability in production for each subject. Perceptual data were collected using a synthesized speech continuum that varied vowel duration. Identification responses were used to calculate category boundary, category separation (slope/boundary width) and variability (response consistency) for each subject. Mean percentage correct discrimination was derived by using two-step and three-step two-pair same different paradigms. The results were as follows: (a) category boundary and category separation in production were adult-like by 8 years of age, (b) variability in production was not adult-like by 10 years of age, (c) perception categorization (category boundary and category separation) was adult-like at 5 years of age, (d) perceptual consistency was not adult-like until 10 years of age, (e) percentage correct discrimination was not adult-like by 10 years of age, (f) correlations between comparable perception and production measures were nonsignificant, and (g) a pairwise comparisons analysis indicated that perception was consistently more advanced than production. PMID- 2601312 TI - Comfortable loudness level: stimulus effects, long-term reliability, and predictability. AB - This paper reports the results of a series of investigations of comfortable loudness levels with particular reference to their application to hearing aid gain prescriptions. Experiment 1 studied the effects of several stimulus waveforms, bandwidths, and durations on comfortable loudness levels for normal and hearing impaired listeners. Speech band comfort levels were found to be significantly higher than equal-duration noise band or warble tone comfort levels. Comfortable loudness levels were found to be independent of warble tone modulation parameters and of stimulus bandwidth (stimuli did not exceed critical bandwidths). In Experiment 2, reliability of comfortable loudness levels was evaluated in hearing-impaired subjects over two consecutive 1-year periods. Results indicated that comfortable loudness levels were slightly less reliable than thresholds. In addition, the results were consistent with a hypothesis that exposure to amplified sound produces a small increase in comfortable loudness levels. In Experiment 3, data from 67 hearing-impaired subjects were used to develop regression equations for prediction of comfortable loudness levels. Thresholds at the test frequencies were combined with comfortable loudness data at 500 Hz and 4,000 Hz. The prediction method was then evaluated using a new group of 25 subjects. Accuracy of predictions of comfort levels was substantially better with the new method than with an older method that relied exclusively on threshold data. Relevance of the outcomes to hearing aid fitting procedures is discussed. PMID- 2601313 TI - Frequency modulation characteristics of sustained /a/ sung in vocal vibrato. AB - Frequency modulation characteristics of sustained vowel phonations in vocal vibrato were investigated. Eight male singers produced sustained /a/ in vibrato at low-, middle-, and high-pitch levels with comfortable loudness. The recorded voice samples were digitized and analyzed by a program yielding a plot of fundamental frequencies (Fo) of individual fundamental cycles. Modulation frequency, extent, rates of Fo increase and decrease, and modulation jitter and modulation shimmer were measured for individual modulation cycles. Central tendency and variability of these measures, intercorrelations among these measures, and temporal patterns of frequency modulations were investigated. Results indicated (1) significant effects of pitch levels on modulation frequency, (2) more regularity in modulation frequency than extent, (3) predominantly linear temporal patterns of frequency modulation, and (4) faster Fo increase than decrease. Implications of these findings for the nature of underlying mechanisms of frequency control in vocal vibrato are discussed. PMID- 2601314 TI - Speech rate reduction and "nasality" in normal speakers. AB - This study explored the effects of reduced speech rate on nasal/voice accelerometric measures and nasality ratings. Nasal/voice accelerometric measures were obtained from normal adults for various speech stimuli and speaking rates. Stimuli included three sentences (one obstruent-loaded, one semivowel-loaded, and one containing a single nasal), and /pv/ syllable trains.. Speakers read the stimuli at their normal rate, half their normal rate, and as slowly as possible. In addition, a computer program paced each speaker at rates of 1, 2, and 3 syllables per second. The nasal/voice accelerometric values revealed significant stimulus effects but no rate effects. The nasality ratings of experienced listeners, evaluated as a function of stimulus and speaking rate, were compared to the accelerometric measures. The nasality scale values demonstrated small, but statistically significant, stimulus and rate effects. However, the nasality percepts were poorly correlated with the nasal/voice accelerometric measures. PMID- 2601315 TI - Temporal-gap detection by cochlear prosthesis users. AB - Minimum-detectable gaps for sinusoidal stimuli were measured for three users of a multi electrode cochlear prosthesis as functions of stimulus level, frequency, and electrode place within the cochlea. Stimulus level was scaled by sensation level and by growth-of-loudness functions generated for each condition by direct magnitude estimation. Minimum-detectable gaps decreased with increase in either sensation level or loudness, up to a plateau. When compared at equal sensation levels, the minimum-detectable gaps decreased with frequency increases. The frequency effect on minimum-detectable gaps is reduced if the data are considered at equal loudness. Comparison across place of stimulation within the cochlea showed minimum-detectable gaps to be shorter for more basal electrode placement at low stimulus levels. No differences in minimum-detectable gap as a function of place were found at higher stimulus levels. PMID- 2601316 TI - Conversational topics of 4-year-olds. AB - Young children's ability to participate in conversation has been of particular interest in the study of pragmatic aspects of language. In this study, topics of conversation were investigated by videotaping 10 dyads of 4-year-old children during play. Ten-minute samples were analyzed according to a number of topic dependent measures. Results revealed that all dyads evidenced some lengthy topics (13-91 utterances). Longer topics were characterized by three text-level functions. Enacting Scenarios, Describing, and Problem Solving. Nevertheless, three fourths of all dialogues were considered relatively short. Generally, partners contributed equally to dialogue, but in some dyads, 1 child dominated initiation. Findings of the study suggest that 4-year-olds are capable of extended participation in dialogue, at least part of the time. Naturalistic play settings may elicit samples of conversation that are representative of preschoolers' ability. PMID- 2601317 TI - Verbal fluency characteristics of normal and aphasic speakers. AB - Fourteen mildly aphasic and 14 normal speakers responded to an oral verbal fluency task for five different semantic categories. Retrieved words were scored within each 15-s time interval of a 60-s task as highly representative (i.e., having a high frequency of occurrence in a previous normative study), moderately representative (i.e., having a moderate frequency of occurrence), or highly unrepresentative (i.e., having a low frequency of occurrence). Both speaker groups were affected similarly by category type, and both retrieved words according to prior data-based notions of semantic categorical organization. The two groups differed with respect to the interaction between time intervals and representativeness levels. The different verbal fluency performance of the aphasic subjects was related to both the temporal occurrence of a word within a 60-s response interval and to its representativeness level (prototypicality) within a particular semantic category. PMID- 2601318 TI - Effects of click rate and electrode orientation on threshold of the auditory brainstem response. AB - This study evaluated the effects of stimulus presentation rate and electrode orientation on ABR threshold. Six normal-hearing adults served as subjects. ABRs were recorded from three orthogonal electrode pairs in response to click stimuli at rates of 48 and 21/s. Psychophysical thresholds were determined for each of these stimuli, and ABRs were recorded with stimuli between 0 and 10 dB SL in 2-dB steps. A ratio of ABR signal strength to noise variance (Fsp) was the criterion used to define threshold. Specifically, an Fsp value of 2.25, equivalent to a 95% response confidence using 5 and 250 degrees of freedom, was the criterion used to determine response presence within a maximum of 10,000 sweeps per average. Results revealed that, for normal-hearing adult subjects, click rate up to 48/s does not influence the sensation level at which a detectable response can be found, and a nearly vertical electrode orientation is optimal for recording the response at low levels. The predicted difference between psychophysical and ABR thresholds with a vertical electrode orientation, using 10,000 sweeps per average, up to 48 clicks per second, and an Fsp criterion of 2.25 is 4.4 dB. PMID- 2601319 TI - Performance of some of the better cochlear-implant patients. AB - The main purpose of this study was to provide an independent corroboration of open-set word recognition in some of the better cochlear-implant patients. These included the Chorimac, Nucleus (one group from the U.S.A. and one group from Hannover, Germany), Symbion, Duren/Cologne and 3M/Vienna implants. Three experiments are reported: (1) word recognition in word lists and in sentences; (2) environmental sound perception, and (3) gap detection. On word recognition, the scores of 6 Chorimac patients averaged 2.5% words and 0.7% words in sentences correct in the French tests. In the German tests, the scores averaged 17% words and 10% words in sentences for 10 Duren/Cologne patients, 15% words and 16% words in sentences for 9 3M/Vienna patients, and 10% words and 16% words in sentences (3% to 26%) for 10 Nucleus/Hannover patients. In the English tests, the scores averaged 11% words and 29.6% words in sentences for 10 Nucleus-U.S.A. patients, and 13.7% words and 35.7% words in sentences for the 9 Symbion patients. The ability to recognize recorded environmental sounds was measured with a closed set of 18 sounds. Performance averaged 23% correct for Chorimac patients, 41% correct for 3M/Vienna patients, 44% correct for Nucleus/Hannover patients, 21% correct for Duren/Cologne patients, 58% correct for Nucleus/U.S.A. patients, and 83% correct for Symbion patients. A multidimensional scaling analysis suggested that patients were, in part, utilizing information about the envelope and about the periodic/aperiodic nature of some of the sounds. Gap detection thresholds with a one-octave wide noise centered at 500 Hz varied widely among patients. Typically, patients with gap thresholds less than 40 ms showed a wide range of performance on speech perception tasks, whereas patients with gap-detection thresholds greater than 40 ms showed poor word recognition skills. PMID- 2601320 TI - The perception of rhythm and word boundaries in noise-masked speech. AB - The present experiment tested the suggestion that human listeners may exploit durational information in speech to parse continuous utterances into words. Listeners were presented with six-syllable unpredictable utterances under noise masking, and were required to judge between alternative word strings as to which best matched the rhythm of the masked utterances. For each utterance there were four alternative strings: (a) an exact rhythmic and word boundary match, (b) a rhythmic mismatch, and (c) two utterances with the same rhythm as the masked utterance, but different word boundary locations. Listeners were clearly able to perceive the rhythm of the masked utterances: The rhythmic mismatch was chosen significantly less often than any other alternative. Within the three rhythmically matched alternatives, the exact match was chosen significantly more often than either word boundary mismatch. Thus, listeners both perceived speech rhythm and used durational cues effectively to locate the position of word boundaries. PMID- 2601322 TI - Peer-related communicative competence of preschool children: developmental and adaptive characteristics. AB - The peer-related communicative interactions of nonhandicapped 3- and 4-year-old children as well as a group of 4-year-old mildly developmentally delayed children were investigated in a cross-sectional descriptive study. Adjustments of speakers to companions varying in terms of chronological age and developmental status were of interest, as were comparisons among the three groups. All three groups made adjustments in communicative functions (directives and information statements), interactive style (strong and joint directives), and communications involving affect (disagreements), but only to mildly delayed children. Adjustments to mildly delayed children were more closely related to interpersonal and social status factors than to children's developmental levels. The communicative interactions of mildly delayed children were highly similar to the developmentally matched nonhandicapped group on all measures except for a lower level of speech complexity. Significant differences between 3- and 4-year-old nonhandicapped children were obtained only for measures of speech complexity. PMID- 2601321 TI - Analytic study of the Tadoma method: effects of hand position on segmental speech perception. AB - In the Tadoma method of communication, deaf-blind individuals receive speech by placing a hand on the face and neck of the talker and monitoring actions associated with speech production. Previous research has documented the speech perception, speech production, and linguistic abilities of highly experienced users of the Tadoma method. The current study was performed to gain further insight into the cues involved in the perception of speech segments through Tadoma. Small-set segmental identification experiments were conducted in which the subjects' access to various types of articulatory information was systematically varied by imposing limitations on the contact of the hand with the face. Results obtained on 3 deaf-blind, highly experienced users of Tadoma were examined in terms of percent-correct scores, information transfer, and reception of speech features for each of sixteen experimental conditions. The results were generally consistent with expectations based on the speech cues assumed to be available in the various hand positions. PMID- 2601323 TI - Closed-set effects in consonant confusion patterns. AB - Invariance of error patterns in confusion matrices of varying dimensions were examined. Normal-hearing young adults were presented closed-set arrangements of digitized syllable tokens, spoken by 1 male and 1 female talker, and selected from a set of 14 consonants (stops and fricatives). Each consonant was paired with the vowel/a/ in a vowel-consonant format and presented at three intensity levels. Patterns of errors among voiceless stops and among voiced fricatives were dependent on the set of alternatives. Voiceless fricatives and voiced stops were not significantly affected by the number of response alternatives. Speaker differences, individual differences among listeners, and implications relating to the generalization of confusion data collected in small closed-set arrangements are discussed. PMID- 2601324 TI - Recent advances in gonadotropins. (Structure, biogenesis, regulation, mechanism of action, clinical and therapeutic applications). Proceedings of the international symposium of La Fondation de Recherche en Hormonologie. Paris, France, 20-22 April 1988. PMID- 2601325 TI - Characterization and structure of ovarian and testicular LH/hCG receptors. AB - Ovarian and Leydig cell LH/hCG receptors purified to homogeneity were identified as a single protein of Mr 80,000 and 90,000 respectively. The homogeneity of this protein was confirmed by microsequencing of the first 18 amino acids of the ovarian receptor. The unblocked N-terminal peptide consisted of NH2-R-E-L-S-G-S-R X-P-E-P-X-D-X-A-P-D-G. These receptors are N-linked sialoglycoproteins which accounts for the size difference between testicular and ovarian receptors and may participate in the interaction with gonadotropin. Crosslinking of pure receptor with hCG with 125I label in either subunit indicated significant interaction of alpha-hCG with the receptor, while beta-hCG seems involved mostly through association and conformational influence on the alpha-subunit. Comparison of Mr derived from SDS with those from FPLC suggested that the native LH receptor are dimers of identical subunits. Autoradiographs of blotted receptors demonstrated that both monomeric and dimeric forms can bind hCG. Receptors from both tissues can be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase and phosphopeptide maps were identical. Receptor occupancy by agonist leads to a conformational change which facilitates its phosphorylation during initial binding and reduces the rate of phosphorylation after more prolonged exposure to gonadotropin. Aggregation or dimerization of the hCG/LH receptors could promote clustering and or crosslinking of receptors in the membrane favouring the initial transduction steps in the action of these hormones. PMID- 2601326 TI - [Quantitation of hCG. Decision boundary and clinical decision threshold]. AB - The clinical decision threshold is defined by the level required to establish the presence of hCG and to measure the quantity. It is different from detection limit because it does not result from a calculation with an error risk but it is experimentally determined. PMID- 2601327 TI - [Methods of quantitating gonadotropins and ovarian steroids]. AB - The immunochemical methods take a preponderant place in the measurement of gonadotropins and ovarian steroids. If the sandwich methods for the ELISA type are almost exclusively used for peptide hormones, the measurement of steroid hormones are necessarily performed by a competition technique. The relatively easy preparation of polyclonal and monoclonal anti-gonadotropin antibodies leads to antibodies with a good specificity for these hormones whereas the anti steroid, specially monoclonal antibodies, are much more difficult to obtain. The different labeling possibilities used in the detection of the antigen-antibody complex, the quality of existing standards and the immunoassay's reliability are successfully discussed. PMID- 2601328 TI - Estrone sulfatase activity in rat brain and pituitary: effects of gonadectomy and the estrous cycle. AB - Estrone sulfatase activity was characterized in microsomal preparations from rat brain and anterior pituitary. No differences in apparent Km were found in hypothalamic-preoptic area between male (7.5 microM) and female (7.4 microM) rats. Apparent Km's of anterior pituitaries from males (14.5 microM) and females (22.5 microM) were higher than those found in brain. Estrone sulfatase activity was equally inhibited by estradiol-17 beta-3-sulfate, dehydroepiandrosterone-3 sulfate and estrone-3-sulfate indicating a broad range of substrate specificity for this enzyme. Sulfatase activity in female anterior pituitary was found to be twice that of male. Sulfatase activity was distributed similarly in brain tissues between sexes with cerebellum greater than or equal to medial basal hypothalamus greater than preoptic area = cortex. Following gonadectomy, sulfatase activity in anterior pituitary of males was significantly greater than activity found in intact animals (P less than 0.05). This increase in activity, however, was unaffected by treatment with testosterone, dihydrotestosterone or estradiol-17 beta. Gonadectomy did not change sulfatase activity in brains of males or females or in pituitaries of females. However, sulfatase activity in pituitary glands of females changed significantly (P less than 0.05) with stages of the estrous cycle (metestrus less than diestrus less than proestrus less than estrus). These data indicate sulfatase activity in rat anterior pituitary gland may be controlled by gonadal factors while sulfatase activity in brain is regulated differently. PMID- 2601329 TI - The histochemistry of oestradiol-17 beta and isocitric dehydrogenases in endometrial carcinoma. AB - Specimens of endometrial carcinoma were obtained from 8 women, four of whom had previously been treated with oral medroxyprogesterone acetate 200 mg daily for 7 days. The activities of oestradiol-17 beta and isocitric dehydrogenases and nuclear oestradiol receptor concentrations were measured in the homogenised tissue and both enzymes were located histochemically. Histochemical evidence of oestradiol dehydrogenase activity was found in all but one of the specimens with biochemical activity. This anomalous specimen was obtained from a woman who had not been treated with MPA and whose endometrium exhibited only low levels of enzyme activity. The histochemical staining caused by isocitric dehydrogenase was intense but bore no relation to the biochemical measurement of enzyme activity in the homogenate. The modified technique for the histochemical demonstration of oestradiol dehydrogenase activity although not quantitative gave results similar to the biochemical methodology. It may therefore be useful as a simple test of the prediction of the sensitivity of endometrial carcinoma to progestogens. PMID- 2601330 TI - Reversible, positive cooperative interaction of 11 beta-chloromethyl [3H]estradiol-17 beta with the calf uterine estrogen receptor. AB - The binding of 11 beta-chloromethyl-[3H]estradiol-17 beta [3H]CME2) with the calf uterine estrogen receptor was investigated. The equilibrium binding analysis indicated a positive cooperative interaction yielding curvilinear Scatchard plots and Hill coefficients of 1.4-1.5. This positive cooperative interaction of [3H]CME2 was indistinguishable from the typical cooperative interaction of [3H]estradiol with the receptor. The apparent relative association constant and the relative binding affinity of CME2 for the estrogen receptor measured by competitive binding assay were 146 and 184%, respectively. The dissociation kinetics of [3H]CME2 from the receptor was biphasic, composed of a fast dissociating component (15%, t1/2 = 4 min at 0 degrees C; 9%, t1/2 = 4 min at 28 degrees C) and a slow dissociating component (85%, t1/2 greater than 50 h at 0 degrees C; 91%, t1/2 greater than 50 h at 28 degrees C). The dissociation kinetics of [3H]estradiol was also biphasic: the t1/2 of the fast dissociating component was 4 min at 0 and 28 degrees C and approximately 200 min for the slow dissociating component at both temperatures. The fraction of the slow [3H]estradiol dissociating component increased from 56 to 92% upon warming. Ethanol extraction and trichloroacetic acid treatment proved that the binding of [3H]CME2 is fully reversible. The unusual dissociation kinetics and the binding mechanism of CME2 are discussed. PMID- 2601331 TI - Estrogen regulation of methyl p-hydroxyphenyllactate hydrolysis: correlation with estrogen stimulation of rat uterine growth. AB - We have recently demonstrated that methyl p-hydroxyphenyllactate (MeHPLA) is the endogenous ligand for nuclear type II binding sites in the rat uterus and other estrogen target and non-target tissues. MeHPLA binds to nuclear type II binding sites with a very high binding affinity (Kd approximately 4-5 nM), blocks uterine growth in vivo, and inhibits MCF-7 human breast cancer cell growth in vitro. Conversely, the free acid (p-hydroxyphenyllactic acid, HPLA) interacts with type II binding sites with a much lower affinity (Kd approximately 200 nM) and does not inhibit estrogen-induced uterine growth in vivo or MCF-7 cell growth in vitro. On the basis of these observations, we suggested that one way that estrogen may override MeHPLA inhibition of rat uterine growth may be to stimulate esterase hydrolysis of MeHPLA to HPLA. The present studies demonstrate that the rat uterus does contain an esterase (mol. wt approximately 50,000) which cleaves MeHPLA to HPLA, and that this enzyme is under estrogen regulation. This conclusion is supported by the observations that MeHPLA esterase activity is increased 2-3-fold above controls within 2-4 h following a single injection of estradiol, and is maintained at high levels for 16-24 h following hormone administration. This sustained elevation of MeHPLA esterase activity correlates with estradiol stimulation of true uterine growth and DNA synthesis. PMID- 2601332 TI - Hydroxylated 2,3-diarylindenes: synthesis, estrogen receptor binding affinity, and binding orientation considerations. AB - In order to develop high affinity, fluorescent ligands for the estrogen receptor based on 2-arylindenes, it is important to understand how this non-steroidal estrogen is oriented within the binding site and to know how hydroxyl substituents affect binding. To investigate these issues a series of dihydroxyl substituted 2,3-diphenylindenes were prepared by the cyclization of appropriately substituted alpha-benzyldesoxybenzoins, and their binding affinities for the estrogen receptor measured by a competitive radiometric binding assay. Introduction of a p-hydroxyl group in the 2-phenyl ring of two 2,3-diphenyl-6 hydroxyindene systems causes a 3-fold increase in binding affinity, whereas, p hydroxylation in the 3-phenyl ring of these systems causes a 2-fold reduction in binding affinity. The parallel change in binding affinity in these two systems suggests a consistent binding orientation of the 2,3-diarylindene systems, which, on the basis of earlier studies, has the indene system corresponding to the A/B ring system of estradiol. This orientation model and the enhanced affinity of the p-hydroxy 2-ring derivatives are suggestive of a new hydrogen bonding site below the D-ring binding site. Changes in receptor binding affinity upon hydroxylation in triphenylacrylonitrile ligands for the estrogen receptor, reported by others, do not show such parallelism, suggesting that different derivatives may not be bound in congruent orientations. A m-hydroxyl substituent in ring-3 of the 2,3 diarylindene has very little effect on receptor binding. In designing fluorescent 2,3-diarylindene ligands for the estrogen receptor, 3-ring hydroxylation may be useful in reducing non-specific binding and in modifying electron donation to the fluorophore with only modest or no reduction in binding affinity. p-Hydroxylation of the 2-ring, although increasing receptor binding, is not consistent with the electron accepting nature required of this ring. PMID- 2601333 TI - An enzyme-linked immunosorbent assay (ELISA) for human corticosteroid-binding globulin. AB - A specific and sensitive enzyme-linked immunosorbent assay (ELISA) of the "sandwich-type" for human corticosteroid-binding globulin was developed. A polyclonal rabbit anti-CBG antibody is immobilised to a microtitre plate. Following incubation of standards and samples a second monospecific rabbit anti CBG antibody, labelled with alkaline phosphatase, is added. After colour development the microtitre plate is read at 405 nm wavelength. The assay shows good agreement to CBG binding capacity assay and commercially available RIA. PMID- 2601334 TI - Renal 21-hydroxylation of 19-hydroxy-progesterone to 19-hydroxy deoxycorticosterone. AB - 19-Nor-deoxycorticosterone (19-nor-DOC) is a mineralocorticoid present in both rat and human urine, and it is elevated in some forms of experimental and human hypertension. Although the exact steps in the biosynthesis of 19-nor-DOC are uncertain, it is probably produced from a 19-oxygenated derivative of DOC, which undergoes 19-desmolation in the kidney. Since DOC biosynthesis is partly due to renal 21-hydroxylation of progesterone (Prog), we sought to determine whether a parallel pathway could exist for the biosynthesis of 19-hydroxy-DOC, a precursor to 19-nor-DOC. In order to test this hypothesis, authentic 19-hydroxy progesterone was incubated with homogenized renal tissues from either rat or human sources. Formation of 19-hydroxy-DOC was found to be the major metabolite in both rat and human incubations, as demonstrated by an HPLC retention time identical to authentic 19-hydroxy-DOC. 19-Hydroxy-DOC formation was further verified by GC/MS analysis with highly sensitive selected ion recording. Since it has been demonstrated that the placenta can convert progesterone to 19-hydroxy progesterone, the renal 21-hydroxylation of 19-hydroxy-progesterone to 19-hydroxy DOC could be an alternate pathway of 19-nor-DOC production especially during pregnancy. PMID- 2601335 TI - Phenol red mimics biological actions of estradiol: enhancement of osteoblast proliferation in vitro and of type I collagen gene expression in bone and uterus of rats in vivo. AB - Since osteoblasts are direct targets for estradiol in vitro, and Phenol Red has been reported to bear estrogen-like bioactivity, we investigated whether the pH indicator also mimicked the biological effects of estradiol on bone cells in vitro. We then asked whether estrogenic effects of Phenol Red could be observed in vivo, firstly on the uterus, and if so, whether Phenol Red could also effect bone in vivo. The proliferation of calvarial osteoblasts was stimulated by commercially available preparations of Phenol Red in a dose-dependent manner at 1.5-50 microM. This effect was not abolished in the presence of an antibody against insulin-like growth factor I. In addition, Phenol Red increased alpha 1 (I) collagen mRNA levels of osteoblasts in vitro. 17 beta-estradiol (1.5 micrograms) or Phenol Red (10 mg) administration to immature female rats (45-50 g) resulted in a weight gain of the uterus, and alpha 1(I) procollagen transcripts were more abundant in RNA prepared from uterus of drug-treated rats than observed in the control rats. Similarly, higher procollagen mRNA steady state levels were observed in RNA prepared from parietal bones of Phenol Red or estradiol-treated rats compared to RNA from control rats. The data extend previous findings in vitro by demonstrating that Phenol Red also exerts estrogen like effects in vivo. Moreover, we show that Phenol Red stimulates bone cells and, therefore, is likely to interfere at least in experiments designed to investigate estrogen effects on osteoblasts. PMID- 2601336 TI - Progestins and androgens stimulate lipid accumulation in T47D breast cancer cells via their own receptors. AB - Using electron microscopy, in the human breast cancer cell line T47D, the synthetic progestin R5020, and 5 alpha-dihydrotestosterone were shown to increase significantly the number of lipid droplets per cell section compared to control cells or estradiol- and dexamethasone-treated cells. Lipid accumulation, as measured by Oil Red O dying and by [2-14C]acetate incorporation, was observed at concentrations as low as 10 pM R5020 and 1 nM 5 alpha-dihydrotestosterone, and was always more abundant after progestin treatment. The progestin antagonist RU486 inhibited, in a dose-dependent manner, lipid accumulation initiated by the two hormones, whereas the androgen antagonist flutamide inhibited only the effect initiated by 5 alpha-dihydrotestosterone. Cytoplasmic lipid droplets accumulation was not observed in the BT20 breast cancer cell line, which contains neither progesterone nor androgen receptors. These results indicate that progestins and androgens increase lipid accumulation by interacting with their own receptor. Chromatographic analysis of [2-14C]acetate labeled lipids showed that R5020 and 5 alpha-dihydrotestosterone enhanced the accumulation of cellular triglycerides at least in part by increasing their synthesis and decreased the quantity of lipids released into the medium. To conclude, we have shown that progestins and androgens, via their own receptor, can induce the same triglyceride accumulation in T47D cells. This effect follows fatty acid synthetase induction and precedes cell growth inhibition, two responses also triggered by progestin and androgen in these cells. PMID- 2601337 TI - The influence of various steroids on the binding of methyltrienolone (R1881) to human placenta: evidence for a second steroid-binding site which stabilizes the R1881 binding site. AB - Specificity studies of the binding of R1881 to crude placental homogenate gave surprising results in that certain steroids increased the binding of [3H]R1881 rather than displacing it. While data for 'competing', i.e. displacing, steroids were similar to those reported by other authors, there have been no previous reports of increased binding due to added steroids. This increased binding was due mainly to an increase in capacity (about 10-fold). These data suggest that the placental steroid-binding protein is unusual in that there is a second steroid-binding site whose occupancy increases the stability of the protein, thereby increasing its capacity to bind R1881. PMID- 2601338 TI - Microbial transformations of steroids--V. Transformation of progesterone by whole cells and extracts of Botryosphaerica obtusa. AB - Members of the genus Botryosphaerica are reported 7 alpha steroid hydroxylators [1]. We found that the species B. obtusa efficiently hydroxylated progesterone in a 1-day transformation but it gave 7 beta-hydroxyprogesterone as the main product rather than the expected 7 alpha-hydroxy isomer, which was produced in only trace amounts. Also formed in minor amounts were 6 beta-, possibly 9 alpha- (see main text), 14 alpha- and 15 beta-monohydroxyprogesterones. The transformation mixtures included appreciable amounts of dihydroxylated progesterones which were mainly based on 7 beta-hydroxyprogesterone. The second hydroxyl group was at one of the minor monohydroxylation sites. The relative concentrations of the progesterone diols increased and those of the mono-alcohols concomitantly decreased when transformation was extended beyond 1 day. Monohydroxylated 6 dehydroprogesterones began to accumulate after about 3 days and these compounds seemed to have been formed by 6,7-dehydration of the dihydroxyprogesterones. We prepared mycelial cell-free extracts which were capable of transforming progesterone and retained the site-specificity of whole cells. These extracts converted 7 beta-hydroxyprogesterone to its 6-dehydro derivative, confirming that ring B desaturation occurs in this organism by dehydration. The dehydratase activity necessary for the conversion was separable from the hydroxylase activity by ultra-centrifugation. All hydroxylase activity co-sedimented with the membrane fraction, implying that steroid hydroxylation is effected by a membrane-bound enzyme(s). Dehydratase activity was present in both the pellet and the supernatant fractions, which suggests that it may involve a loosely bound, and easily removed, membrane-associated enzyme. PMID- 2601339 TI - Effect of human chorionic gonadotropin and prostaglandin F2a on progesterone production by human luteal cells. AB - To determine and compare the direct effects of prostaglandin F2a (PGF2a) and human chorionic gonadotropin (hCG) on luteal cell progesterone production in vitro, 9 human corpora lutea obtained at tubal ligation were minced and treated with collagenase to disaggregate luteal cells. Dispersed luteal cells (80% viable) were incubated in air at 37 degrees C in a shaking water bath for 3 h and total progesterone in the media and cells was determined by radioimmunoassay. Optimum progesterone production was obtained using 25,000 or more cells per incubate and an incubation time of 2-4 h. hCG-stimulated progesterone production increased significantly with 0.01 IU to as high as 100 IU. In the early luteal phase (days 1-5 post ovulation or days 15-20 of the luteal phase), PGF2a (10-1000 ng) significantly inhibited progesterone production but significantly stimulated progesterone production in the mid-luteal phase (days 21-25). PGF2a had no effect on luteal cell progesterone production in the late luteal phase (days 26-30). This age-dependent direct effect of PGF2a on human luteal cell progesterone production in vitro indicates a role for PGF2a in the total intragonadal regulation of progesterone output, possibly through a paracrine or autocrine manner directed towards synchronizing luteal progesterone secretion and endometrial preparation for nidation. PMID- 2601340 TI - Androgen and 19-norandrogen aromatization by equine and human placental microsomes. AB - The ability of equine and human placental microsomes to aromatize testosterone and 19-nortestosterone was studied. When 3 microM [1 beta,2 beta-3H]testosterone was used as substrate, the specific activity of equine placental microsomal aromatase was 2.5 times higher than that of the human microsomal enzyme. Although 19-nortestosterone was aromatized 67 times more rapidly by equine than by human aromatase, we found that equine aromatase exhibited a markedly weaker affinity for this substrate than did the human enzyme. Competitive inhibition of testosterone aromatization by 19-nortestosterone occurred with both equine and human aromatases. While having no effect on mare placental microsomes, Na+ and K+ (500 mM) stimulated testosterone aromatization by human placental microsomes by 73 and 52% respectively. If indeed a single enzyme is responsible for the aromatization of testosterone and 19-nortestosterone, which seems to be the case in both equine and human placental aromatase, our results show that differences in the structure of the active sites exist between equine and human aromatases. PMID- 2601341 TI - Changes in nuclear protein pattern by glucocorticoid treatment of lymphoid cells. AB - Glucocorticoids initiate a cytolytic process in lymphoid cells. The ultimate response is preceded by several phenomena. It is generally accepted that these are mediated through messenger proteins. The induction of these proteins is considered the primary effect of glucocorticoids. However, as yet specific gene products have not been identified. In electrophoretic assays, we observed an increased concentration of 6 nuclear proteins within a few hours of exposure of lymphoid cells to glucocorticoids. These proteins displayed prominent DNase activity. However, further studies showed: (1) that the proteins concerned are histones, (2) that histones are more easily extracted after glucocorticoid induced alterations of lymphoid cells, and (3) that basic proteins in general express nuclease activity under certain experimental conditions. This nuclease activity is, however, artifactual. Therefore, though the changes observed are certainly related to glucocorticoid-induced effects, these do not reflect the induction of specific proteins. The results of the study indicate that glucocorticoid-induced changes in the concentration of cellular proteins should be interpreted with caution. PMID- 2601342 TI - Detection of two high molecular weight hydrophobic forms of the human estrogen receptor. AB - The human estrogen receptor gene encodes a single protein of molecular weight 65,000 daltons. However, using a sensitive and rapid technique of high performance hydrophobic interaction chromatography we have detected two distinct estrogen receptor species both of which are high molecular weight proteins (ca. 60A) as determined by high-performance size-exclusion chromatography. These are detected either in the presence or absence of sodium molybdate; rechromatography of individual isoform indicates that the two protein complexes have independent hydrophobic contact points. Consistent elution patterns of the two receptor species indicates they are formed selectively. We conclude that different post translational modifications of the estrogen receptor protein could allow their specific interaction with non-receptor components resulting in the formation of two distinct high molecular weight complexes which would be rapidly resolved by high-performance hydrophobic interaction chromatography. PMID- 2601343 TI - Evidence of formation of isomeric methoximes from 20-oxosteroids. AB - The formation and gas chromatographic behavior of syn- and anti-isomers in position 20 of the methoxime-trimethylsilyl (MO-TMS) derivatives of many 20-oxo and 3,20-dioxo-21-hydroxysteroids is reported. The existence of such isomers was established from the gas chromatographic (GC) and mass spectrometric analysis of the MO-TMS derivatives of 3 alpha,21-dihydroxy-5 beta-pregnan-20-one and its 17 alpha-epimer. The degree of separation during GC analysis of the syn- and anti isomers in position 20, as well as those in position 3, is associated to the position of additional hydroxyl groups on the steroid ring. These data are very important for the location of oxygenated substituents such as 2 alpha/2 beta, 6 alpha/6 beta, 11 beta, 16 alpha, 17 alpha, 18, 19 or 21-hydroxyl groups during structural studies of 20-oxo and 3,20-dioxosteroids. PMID- 2601344 TI - Characteristics of the rat prostate androgen receptors analyzed by sucrose density gradient and high-performance liquid chromatofocusing. AB - Rat prostate cytosolic androgen-receptor complexes were analyzed by sucrose density gradient (SDG) centrifugation and by high-performance liquid chromatofocusing (HPCF). Without protecting agents, these complexes were resolved by HPCF at basic (8.25-7.1), intermediary (7.0-5.0) and acidic (4.6-4.2) pH. Sodium molybdate stabilized labeled complexes which migrated in the 8-9S and 3.5 6S areas on SDG. These were further stabilized by the presence of sodium molybdate and four protease inhibitors: complexes then sedimented mainly in the 8 9S area with a shoulder at 6-7S. Forms eluting at acidic pH on HPCF were favored by the presence of sodium molybdate and further enhanced by the addition of inhibitors, to the detriment of basic ones. Furthermore, when chromatographed on phosphocellulose (P-c), unretained complexes sedimented as a symmetrical peak on SDG centrifugation in the 8-9S area, but were eluted from HPCF columns as two entities at pH 4.1 and 4.6. The P-c retained complexes subsequently detached by 0.6 M KCl, were resolved into three entities by HPCF with a major component at pH 8.2, which sedimented in the 4S areas. These results demonstrate that the gradual decrease in the negative net charge of androgen receptor correlates with the gradual reduction in mass of the androgen-receptor complex. Moreover, this can be interpreted as further evidence for a heterogeneity of androgen receptor population in rat prostate, suggesting the involvement of a multistep mechanism preceding the induction of specific gene transcription by the hormone. PMID- 2601345 TI - A mathematical model of the exercise functional state of the oxygen transport system. AB - Based on the principle of minimum power, a mathematical model of the exercise functional state of the oxygen transport system is presented. Aerobic and anaerobic muscular efficiencies are considered. The energetically optimal arteriovenous oxygen content difference, cardiac output and ventilation during exercise in man are determined depending on mechanical power. Theoretical results are compared with experimental data. PMID- 2601346 TI - A statistical mechanical model of the pre- and subtransitions of lecithin membranes. AB - A statistical mechanical model with experimentally proved facts as starting points is presented. This model explains on molecular level, the pre- and subtransitions appearing in lipid membranes. The model describes the main features of the transitions, the hysteresis of the subtransition and the mobility changes of the heads and chains at these transitions. The model was expanded for phosphatidylcholine homologues with arbitrary chain lengths, and a qualitative agreement in the case of pretransition as far as a quantitative one for the subtransition were found. PMID- 2601347 TI - On surface geometry coupled to morphogen. AB - An expression is derived for both the Gauss and the Mean curvature of a surface, in terms of three simple cell parameters. The surface is thought of as composed of a single-cell thick sheet of cells joined laterally. The three cellular parameters involved are the ratios of (linear) basal to apical dimension in two orthogonal directions, S1 and S2, and the cell thickness "h". These three parameters may be envisioned as functions of a morphogen or morphogens which vary from point to point over the (middle) surface. As an example, the "reaction diffusion" equations which are often used to describe pattern-formation in early development can be seen as possible candidates for these morphogens, when the resultant surface deformations are given when the dependence of the three cellular parameters are specified as a function of morphogen concentration. The coupling back of the surface deformations to the set of reaction-diffusion equations is simply given, and is through the dependence on geometry of the Laplacian operator which enters these equations. PMID- 2601348 TI - The domain model for eukaryotic DNA organization. 2: A molecular basis for constraints on development and evolution. AB - A model for eukaryotic DNA organization has been proposed in which DNA regulatory processes depend on multiple site-specific DNA-nuclear matrix interactions throughout a DNA domain. In this model gene regulation depends on combinations of a few control factors in a cell to activate cell type-specific genes. This model suggests simple molecular mechanisms for organismal development which can account for sequential activation of appropriate groups of genes throughout development and for specific constraints on developmental pathways. Additionally, these suggested developmental pathways are consistent with mechanisms of evolution in which gradualism and punctuated equilibrium are not exclusive of one another and are interrelated mechanisms of evolution that are both induced by specific chromosomal mutations. PMID- 2601349 TI - Bioelectrorheological model of the cell. 1. Analysis of stresses and deformations. AB - An electrorheological model of a cell in alternating electric field is proposed. The model relates changes in the spherical cell's shape to the field conditions, electric parameters of cytoplasm, cell membrane and external medium, and to the rheological parameters of the membrane. Stresses were determined using Maxwell's stress tensor for isotropic media. Shear stresses in the cell membrane were analyzed. Predictions of the model for variations of shear stress in cellular membranes subjected to an external periodic electric field are presented and related to the conditions prevailing in electrobiological research. PMID- 2601350 TI - Theoretical response of a bifurcating axon with a locally altered axial resistivity. AB - A short region of high axial resistivity at one daughter branch of an axonal bifurcation can produce frequency dependent differential conduction of action potentials. The increase in resistivity need be only a few times that in the rest of the axon and length of the affected region need be only a fraction of a resting length constant (based on the local value of axial resistivity). The typical pattern observed will be that the unaffected daughter branch will conduct action potentials from the parent axon normally at all frequencies of stimulation, but the branch with the high resistance region will only follow action potentials within a restricted frequency range. In that band-pass region, the branch may conduct nearly all or only a small percentage of the action potentials from the parent axon. PMID- 2601351 TI - Study of Rwandese medicinal plants used in the treatment of diarrhoea I. AB - A series of 20 medicinal plants used in the Rwandese traditional medicine to treat diarrhoeal diseases has been screened for antibacterial activity against several Salmonella and Shigella and for antidiarrhoeal activity on mice. Fifty percent of the plants tested showed antibacterial activity against one or more microorganisms and 65% showed antidiarrhoeal activity. PMID- 2601352 TI - Effects of the gut-stimulating principle in Croton penduliflorus seed oil on the central nervous system. AB - The gut-stimulating principle in Croton penduliflorus seed oil isolated as white crystals (CP crystals) significantly reduced pentobarbitone-induced sleeping time in mice at doses of 3 and 6 mg/kg intraperitoneally. Indomethacin (4 mg/kg) and atropine (0.044 mg/kg) significantly reversed the action of CP crystals on pentobarbitone sleeping time with indomethacin having a profound reversal effect. CP crystals significantly reduced the mean onset of convulsions and the mean death time in mice treated with a surely convulsive dose of strychnine. CP crystals significantly reduced the intensity of morphine and pethidine analgesia and prolonged the duration of pethidine analgesia. Most actions of CP crystals suggest that it stimulates the CNS and reduces the intensity of opioids (except codeine) while prolonging their duration of analgesic action. PMID- 2601353 TI - The hepatoprotective principle of Hypoestes triflora leaves. AB - Hypoestes triflora is frequently used in Rwandese native medicine to treat hepatic diseases. Premedication with a water extract of the leaves prevented the prolongation of the barbiturate sleeping time associated with carbon tetrachloride-induced liver damage in mice. The compound responsible for this protective activity was benzoic acid. Mice previously treated with benzoic acid also showed a significant diminution of the increased GOT and GPT levels seen after carbon tetrachloride administration. PMID- 2601355 TI - Medicinal system of Ladakh, India. AB - The paper presents a detailed study of an ancient medical system of the Old World. The system, popularly known as the "Amchi System", has a large following in Ladakh or Little Tibet (India) and has been practised for centuries. The system resembles, in some broad aspects, the Ayurvedic system but has its own characteristics. It makes use of minerals, hot water springs, puncturing of veins, branding, and herbs. Some of the herbs used by local medical practitioners, popularly known as "Amchis" are also described. Uses of most of the herbs are reported here for the first time. PMID- 2601354 TI - Vascular dilatory action of Artemisia capillaris bud extracts and their active constituent. AB - In perfusion experiments, the acetone extract of Artemisia capillaris buds significantly inhibited the response to norepinephrine of helical strips of rabbit thoracic aorta. The acetone extract was fractionated by column chromatography to identify the active constituent. Kinetic experiments using rabbit thoracic aorta showed that 6,7-dimethoxycoumarin (scoparone) has a marked inhibitory effect on the contractions induced by norepinephrine, 5 hydroxytryptamine, histamine and angiotensin II. Like nitroglycerin, scoparone appeared to be a competitive antagonist of norepinephrine. PMID- 2601356 TI - Anti-inflammatory activity of some Iraqi plants using intact rats. AB - Five plants (Myrtus communis, Apium graveolens, Matricaria chamomilla, Withania somnifera and Achillea santolina) grown in Iraq were assessed for their anti inflammatory activity on intact rats by measuring the suppression of carrageenan induced paw edema produced by 1/10 of the intraperitoneal LD50 doses for the respective 80% ethanol extracts. Acetylsalicylic acid was used as the standard drug. Results showed that the plants possessed varying degrees of anti inflammatory activity and were classified in the following descending order of activity: W. somnifera greater than A. graveolens greater than A. santolina greater than M. chamomilla greater than M. communis. PMID- 2601357 TI - Immunodulatory compounds from Picrorhiza kurroa: isolation and characterization of two anti-complementary polymeric fractions from an aqueous root extract. AB - Two aqueous root extracts of Picrorhiza kurroa, one prepared by extraction at 4 degrees C and the other by refluxing, were purified using the guidance of modulation of classical (CP) and alternative (AP) pathway complement activity. By means of methanol extraction and gel filtration chromatography, two polymeric fractions were isolated from the cold water extract. A methanol-soluble polymeric fraction (CS1) was highly active in inhibiting CP complement activity exclusively, whereas a methanol-insoluble polymeric fraction (CI1) exhibited an inhibitory effect on both CP and AP complement activity. Preliminary chemical analysis of the anti-complementary fractions revealed the presence of structures of carbohydrate and of peptide nature in CS1 and CI1. The modulation of CP complement activity by CS1 was studied in more detail. Its inhibitory effect was proven to be based on complement consumption rather than on chelation of Ca2+ and/or Mg2+ or on stabilization of the target cells in the complement-assay. The purification of the aqueous extract prepared by refluxing, resulted in the isolation of a polymeric fraction with the same qualities as CS1. However, a fraction with properties similar to CI1 could not be isolated from this extract. PMID- 2601358 TI - In vitro and in vivo bronchorelaxant effect in guinea pigs of "joshina"--a herbal polypharmaceutical. PMID- 2601359 TI - Preliminary study of an extract from Diodia scandens on some toxic effects of Echis carinatus venom. PMID- 2601360 TI - Pharmacological screening and antimicrobial activity of the essential oil of Artemisia caerulescens subsp. gallica. PMID- 2601362 TI - Physicochemical and pharmacological properties of spray-dried powders from Fraxinus excelsior leaf extracts. PMID- 2601361 TI - Studies on some medicinal plants of Senegal: effects on isolated guinea pig ileum. PMID- 2601363 TI - [The breech partogram]. AB - A partogram was made after analysis 383 spontaneous breech deliveries of primiparas and 343 of multiparas. The height of parturients was 160 cm or more, gestational age between 37 and 42 weeks and the newborn birthweight between 2500 and 3900 g. The newborns did not show any signs of fetal damage from the period of pregnancy or delivery. The duration of delivery was counted from the time of the cervical dilatation of 2 cm or more. A partogram was made after the statistical analysis of particular cervical dilatation phases; the duration of delivery in primiparas was up to 13 hours and 15 minutes and in multiparas up to 10 hours and 40 minutes. The second stage of delivery in primiparas was 1 hour and 20 minutes and in multiparas 40 minutes. The distribution of data concerning the duration of delivery demonstrated by the mean value and SD was symmetrical; the mean value of the duration of delivery with 99% of reliability was from 9 hours up to 10 hours and 54 minutes for primiparas and from 8 hours and 19 minutes up to 9 hours, and 18 minutes for multiparas. Breech delivery was accelerated in the earlier dilatation phase if compared to the later phase which was significantly slowed down. PMID- 2601364 TI - [Cervicography--a useful method for the early detection of changes in the uterine cervix]. AB - Cervicographic findings were analysed in 156 patients of whom 71 had previously been found to have cervical changes (group I) and 85 were regularly examined within the periodic systematic examination programme (group II). In group I there were 15.5% negative cervicographic findings, 80.3% suspect, and 4.2% technically inadequate. Out of suspect findings, carcinoma in situ or invasive carcinoma were detected in 54.4%, of which 9.7% were cytologically false negative. In group II, in 69.4% of cases, some colposcopic changes (non-malignant) were observed, while in 3 out of 26 colposcopically normal findings, there were some changes in the cervicogram. PMID- 2601365 TI - [Genetic counseling--a qualitative element in family planning]. AB - The number of known hereditary diseases is constantly on the increase. In Yugoslavia, about 1800 children a year are estimated to be born with severe chromosomal anomalies (about 0.5% of all newborns). Nowadays, potential parents are given much chance of controlling the biological quality of their offspring by means of genetic counselling. The authors have systematized indications for genetic counselling according to data on the pregnant woman and her sexual partner, their family history and ancestors. Also the frequency of indications for genetic counselling is assessed, ranging from about 1% of the total population of pregnant women in view of the risk of chromosomopathies to 10-15% in view of habitual abortions in the anamnesis. PMID- 2601366 TI - [Extraperitoneal transabdominal vacuum drainage of the parametrial cavity and suprapubic drainage of the urinary bladder after radical hysterectomy]. AB - Parametral cavity drainage was performed by the Penrose method after Wertheim's operation. In 14.4% of the patients inflammations were observed. After the introduction of extraperitoneal transabdominal vacuum drainage, the percentage of such complications decreased to 5%. In the previously performed transurethral urinary bladder drainage, the authors found uroinfections in 42.6% of the operated patients, whereas following the suprapubic drainage, urine samples remained bacteriologically clear, with less than 100,000 germs per 1 ml. In only one patient with suprapubic drainage, salt accumulated on the catheter, requiring removal by means of surgery cystoscope. PMID- 2601367 TI - [The importance of directed cytological examinations in the diagnosis of ovarian tumors]. AB - A total of 263 cytologically examined patients with clinically suspected ovarian tumours are presented. In 164 cases (58 malignant and 106 benign tumours), the cytological finding and the definite pathohistological diagnosis were comparable, by which it has been found that the sensitivity of the method was 79.3%, its specificity 96.2%, and its predictive value 92.0%. Possible causes of false negative and false positive findings are analysed. PMID- 2601368 TI - [Histologic type and tumor maturity as prognostic factors in malignant epithelial tumors of the ovary]. AB - A retrospective pathological analysis of 664 patients with malignant ovarian epithelial tumors of coelom epithelium origin was performed. In 93 cases (14%) proliferative tumors were found. Out of the remaining 571 cases a group of 311 cases with the five-year survival in the period 1965-1980 was singled out (39.9% invasive and 98% proliferative tumors). The clinical staging of the illness is the most important prognostic factor. In the clinical stage I the five-years survival was 78.8%, the difference being statistically not significant in relation to the histological maturity of the tumors. For any further clinical stage the five-year rate of survival decreased by about 30%. In the clinical stages II, III and IV survival statistically significantly differed (p less than 0.01) with regard to the histological grade of maturity I, whereas the survival was almost the same in cases with moderately or poorly differentiated tumors. Regardless of the clinical stage of the illness, the five-year survival rate for histological grade I was 71.8%, for grade II 24.5% and for grade III 20.4%. According to the histological type of the tumors, the best prognosis is for mucinous cancers, where the five-year rate of survival was 51.4%, and the worst for undifferentiated (13.3%) and clear-cell cancers (16.7%). PMID- 2601369 TI - [School absenteeism in adolescent girls due to gynecologic diseases and conditions]. AB - A distribution is made of excuse for the non-attendance at school of adolescent girls, by which two groups of health disorders could be distinguished, one group including excuses for the non-attendance of up to one day for painful syndromes, contraception, menstrual trouble, examinations for suspected pregnancy, vaginal candidiasis, condyloma, pediculosis, and the inflammation of the urinary bladder, and the other group including excuses for the non-attendance of 2-5 days for non specific inflammations of the vagina, vulva and cervix, abortion, pelvic inflammatory disorders, vaginal trichomoniasis, and injuries. Rarely encountered disorders were dealt with from case to case. The highest average number of excuse days (4.8) related to abortion. The excuse made most frequently (220) were those relating to painful syndromes, 48.1% of the total number of the excuse, averaging 1.2 days per excuse. The total average per excuse was 1.6 days. PMID- 2601370 TI - [Extirpation, Douglas space]. PMID- 2601371 TI - [Results of CA-125 tumor marker determination in patients with ovarian carcinoma]. AB - The serum level of tumor marker CA-125 was determined by a specific immunoradiometric assay in 45 healthy persons (control group), in patients with benign ovarian tumors (13), patients with ovarian carcinoma in remission (15) and progression (28), patients with non-ovarian carcinoma (39), patients with benign peritoneal processes (6), and patients with malignant (3) or inflammatory (10) hepatic diseases. A follow-up study was carried out for a few months (4-11) in some patients after the primary therapy for ovarian cancer. The serum levels of CA-125 were always below the border value (30 U/ml) in healthy persons, in patients with benign ovarian tumors (without peritoneal affection), in patients with ovarian cancer in remission, patients with extraovarian cancers without metastases or with extraperitoneal metastases, and in patients with acute viral hepatitis. Patients with the progression of ovarian carcinoma and patients with peritoneal affection (malignant or benign) had elevated CA-125 values. The findings were in a good correlation with the clinical course in the follow-up study. PMID- 2601372 TI - [Potassium diffusion potentials in fetal erythrocytes and leukocytes in umbilical cord blood]. AB - The potential of the membrane erythrocytes and leucocytes from the fetal umbilical cord blood was studied in order to determine the vitality of cells. The membrane erythrocytes potential was analysed in 11 blood samples of normal deliveries and 3 blood samples of deliveries with the meconium amniotic fluid; the membrane leucocyte potential was examined in 16 blood samples of normal deliveries and 5 blood samples of deliveries with the meconium amniotic fluid. The method used was the indirect fluorescence spectroscopy and the cyanin dye DIO C5-(3) as the extrinsic fluorescent probe. In deliveries with the meconium amniotic fluid, leucocyte and erythrocyte membranes continue maintaining the potassium potential. The reactions of erythrocytes and leucocytes to the addition of valinomycin are entirely different: in the leucocytes of fetuses with the meconium amniotic fluid the membrane is more polarized than in fetuses from normal deliveries, whereas in the erythrocytes of fetuses with the meconium amniotic fluid the membrane polarization is less pronounced. PMID- 2601374 TI - [Modern medical care and hospitals]. PMID- 2601373 TI - [Prolactin in the serum of mothers and neonates and in the amniotic fluid of pregnant women with hypertensive disease]. AB - In 106 pregnant women (32-41 gestation weeks) prolactin values were determined in the sera of mothers and fetuses and in the amniotic fluid by the radioimmunological method in m IU L. Four group of parturients and their newborns were examined: Group I (n = 18) contained parturients with hypertensive disease and pre-term delivery, group II (n = 27) parturients with pre-term delivery, group III (n = 25) parturients with hypertensive disease and at-term delivery, and group IV (n = 36) normal parturients with at-term delivery. Prolactin values (mean +/- SD) in the serum of parturients with pre-term delivery (group I 8,311 +/- 2,654 and group II 8,203 +/- 2,647) and in those with at-term delivery (group III 9,656 +/- 3,145 and group IV 9,873 +/- 3,062) showed no significant differences (p greater than 0.05). Prolactin values in the serum of the umbilical cord artery proved significantly higher (p less than 0.05) in parturients with pre-term delivery (group I 11,598 +/- 2,923, group II 9,632 +/- 3,009) and at term delivery (group III 13,266 +/- 3,015, group IV 11,243 +/- 3,123) in hypertension-affected women. A significantly higher (p less than 0.01) prolactin value was recorded in the amniotic fluid of parturients with pre-term delivery (group I 23,367 +/- 3,896, group II 19,715 +/- 4,128) and at-term delivery (group III 22,755 +/- 4,938, group IV 18,638 +/- 4,724) affected by hypertensive disease. The difference between the prolactin level in parturients with the meconium and clear amniotic fluid (22,059 +/- 5,465 and 19,263 +/- 5,673) was not significant (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601376 TI - [Preparation of medical records in clinical training]. PMID- 2601375 TI - [Difference between clinical training and classroom lessons]. PMID- 2601378 TI - [Interactions with aged patients in clinical training]. PMID- 2601377 TI - [Interactions with terminal patients in clinical training]. PMID- 2601380 TI - [Dealing with pediatric patients in clinical training]. PMID- 2601379 TI - [Interactions with young adult patients in clinical training]. PMID- 2601381 TI - [Dealing with patients' families in clinical training]. PMID- 2601382 TI - [Relationship with clinical instructors in clinical training]. PMID- 2601383 TI - [Relationship with staff nurses in clinical training]. PMID- 2601384 TI - [Relationship with other health professionals in clinical training]. PMID- 2601386 TI - [Organization of conferences in clinical training]. PMID- 2601385 TI - [Encounter in clinical training--encounter within a group as an encounter of self]. PMID- 2601387 TI - [Preparation of a report in clinical training]. PMID- 2601388 TI - [Key points in clinical training]. PMID- 2601389 TI - [Key points in clinical training: psychiatry]. PMID- 2601391 TI - [Key points in clinical training: dermatology]. PMID- 2601390 TI - [Key points in clinical training: orthopedic surgery]. PMID- 2601392 TI - [Key points in clinical training: urology]. PMID- 2601393 TI - [Key points in clinical training: ophthalmology]. PMID- 2601394 TI - [Key points in clinical training: otorhinolaryngology]. PMID- 2601395 TI - [Key points in clinical training: pediatrics]. PMID- 2601396 TI - [Key points in clinical training: Gyneco-obstetrics]. PMID- 2601397 TI - [Key points in clinical training: at the operating room]. PMID- 2601398 TI - [Key points in clinical training: at the ICU and CCU]. PMID- 2601399 TI - [Key points in clinical training: the emergency department]. PMID- 2601401 TI - [Key points in clinical training: in home nursing]. PMID- 2601400 TI - [Key points in clinical training: at the public health clinic]. PMID- 2601402 TI - [Key points in clinical training: at the home for the aged]. PMID- 2601403 TI - [Key points in clinical training: comprehensive nursing training]. PMID- 2601404 TI - Lymphatics of the cardiac chordae tendineae with particular consideration of their origin. AB - We traced the origin of lymphatic capillaries of the chordae tendineae by serial ultrathin sections and electron microscopy of lymphatics identified first by light microscopy at the base of the chordae tendineae. Most of the lymphatics appear flattened in cross section, approximately 15 to 20 microns and 3 to 5 microns in greater and lesser diameters, respectively. Spiny (thorn-like) branchlets (about 10 microns in length) randomly projected from the sides of straight lymphatic capillaries and each was composed of a single endothelial cell with marginal zones in apposition to one another. The extreme end of a straight lymphatic capillary terminated blindly and consisted of a single endothelial cell with an ultrastructural appearance that resembled that of the spiny branchlets. PMID- 2601405 TI - Primary chylocolporrhea successfully managed by division and ligation of retroperitoneal lymphatics. AB - Chylocolporrhea or chylous vaginal discharge is a rare manifestation of the primary chylous reflux syndrome. We describe its occurrence in a young child successfully treated by ligation of retroperitoneal, groin, and vaginal megalymphatics. PMID- 2601406 TI - Macrophages and carcinoma cells migrate at the same pace to the lymph nodes. PMID- 2601407 TI - Alternative pathways for drainage of cerebrospinal fluid in the canine brain. AB - Although the brain has no formal lymphatic system, a substantial quantity of cerebrospinal fluid (CSF) has nonetheless been shown to drain via cervical lymphatics. To pursue further the issue of alternative drainage pathways for CSF, we infused a solution of Ringer's lactate (RL) into the cisterna magna of the dog brain and monitored both the flow and concentration of total protein of cervical lymph. This maneuver promoted a nearly three-fold rise in intracranial pressure and was accompanied by a rise in cervical lymph flow and fall in its protein content. In addition, a profuse nasal discharge (11.4 ml/hr) developed with a moderately high protein content of the rhinorrhea fluid (1.8 g/dl), along with similar appearance times of Evans blue dye (instilled in the cisterna magna) in both cervical lymph and the rhinorrhea fluid (48-70 minutes after infusion). These findings suggest alternative drainage pathways for CSF besides the arachnoid villi (Pacchionian bodies) including connections with lymphatics in the neck and along the olfactory nerve, and around the cribiform plate to the nasal submucosa, and with proptosis, perhaps also through the aqueous humor-canal of Schlemm and nasolacrimal duct. PMID- 2601408 TI - Retroperitoneal lymph nodal visualization using 30% Guajazulen blue (chromolymphography). AB - Guajazulen, a dark blue lipid-soluble dye was used to stain retroperitoneal lymph nodes before lymphadenectomy. Initially, a 30% solution of Guajazulen (Merck, Darmstadt, FRG) in iodinated oil (Lipiodol, Byk-Gulden, Konstant, FRG) was injected endolymphatically in the hindlimbs of pigs (n = 10) and dogs (n = 8) to better visualize retroperitoneal lymph nodes. Because of encouraging results, 11 patients with testicular cancer undergoing staging or therapeutic laparotomy underwent endolymphatic injection of this dye solution preoperatively. The excellent staining of retroperitoneal lymph nodes facilitated nodal selectivity during lymphadenectomy. PMID- 2601409 TI - Lipoperoxide in dog thoracic duct lymph. AB - Lipoperoxide levels were examined in thoracic duct lymph (TDL) of 11 dogs. In four dogs with sodium citrate added in vitro to prevent coagulation, TDL had notably higher levels than in serum. After centrifugation, however, lymph supernatant levels of lipoperoxide closely approximated that in serum suggesting that the bulk of lipoperoxide remained in the sediment and derived from circulating cells. Interstitial accumulation of lipoperoxide, a breakdown product of cell membranes, may be a potent "toxic factor" responsible for trophic changes associated with chronic lymph-edema. PMID- 2601410 TI - Late effects of polio of concern to Maine people. PMID- 2601412 TI - Hurricane Hugo--one nurse's perspective. PMID- 2601411 TI - Who cares? PMID- 2601413 TI - Management of mild hypertension. AB - The benefits of blood pressure reduction have been clearly established for diastolic pressures of more than 100 mm Hg. For patients with a diastolic pressure between 90 and 99 mm Hg on repeated measurements, treatment should be initiated if other risk factors are present--for example, a family history of coronary risk, increased cholesterol level, male sex, smoking, or diabetes mellitus. When the pressure seems to be labile or exaggerated in the office, home or ambulatory readings may provide confirmatory information. For persons with diastolic pressures in the range of 90 to 94 mm Hg, it may be suitable to initiate therapy with nonpharmacologic maneuvers such as sodium restriction, weight reduction, and physical conditioning. In such cases, careful follow-up of blood pressure is particularly important because it may increase later. The initial therapy for mild hypertension should be selected to minimize adverse effects and should be tailored to the individual patient. Management of all levels of hypertension must be considered in light of the associated risk factors and a concomitant effort to minimize cardiovascular risk. PMID- 2601414 TI - Aging increases adenosine and inosine release by human fibroblast cultures. AB - The effect of in vitro age and donor age on net release of adenosine and inosine was studied in cultures of normal human fibroblasts. Confluent cultures of low (population doubling level [PDL] 23-25) and high- (PDL 43-45) passage human lung fibroblasts derived from a 16-week-old fetal donor (IMR-90) were incubated for 30 min in physiological saline and the release of adenosine and inosine into the saline was determined by HPLC. Release of adenosine and inosine into the saline bathing low-passage human skin fibroblasts derived from a 16-week-old fetal donor (GM6111) was also determined and compared with two strains of low-passage skin fibroblasts from aged (66-67 years) donors (GM3529 and GM3524). The release of adenosine and inosine by low-passage cultures of fetal lung fibroblasts was 911 and 225 pmol/30 min per mg protein, respectively. In high-passage cultures of lung fibroblasts, release of adenosine and inosine was significantly greater at 1403 and 351 pmol/30 min per mg protein, respectively. The release of adenosine and inosine by low-passage cultures of fetal skin fibroblasts was 250 and 179 pmol/30 min per mg protein, respectively. In low-passage skin fibroblasts from aged donors, release of adenosine and inosine was significantly greater at 583 and 652 pmol/30 min per mg protein, respectively. These results indicate that the net release of adenosine and inosine by cultured human fibroblasts into their extracellular environment is enhanced by in vitro aging of lung fibroblasts and is greater in skin fibroblast from aged donors. PMID- 2601415 TI - Changes of mouse brain gangliosides during aging from young adult until senescence. AB - The brain gangliosides from young adult to senescent mice (BDF1 and C57BL/6) were studied. The total ganglioside concentrations of the whole brains were almost constant from young adulthood until the beginning of senescence, but decreased constant from young adulthood until the beginning of senescence, but decreased during senescence to about 80% of the constant level observed at the period before the beginning of senescence. In spite of the constancy of the ganglioside concentrations at the period before the beginning of senescence, the composition gradually changed, with an increase of GM1 and decreases of GD1b, GT1b and GQ1b. During the senescence, all of the gangliosides decreased in their concentrations, but GD1a, GT1b and GQ1b decreased to a markedly greater extent (GT1b greater than GD1a greater than GQ1b). The regional gangliosides in olfactory bulb, cerebrum cortex, cerebrum white matter, hippocampus, hypothalamus, cerebellum and medulla oblongata were compared between 3- and 30-month-old mice of both strains. Significant changes in ganglioside concentrations were observed in both strains in the cerebrum and the hippocampus. In the cerebrum white matter, cerebellum and medulla oblongata, GM1 and GM4 contents significantly increased in the senescent mice. PMID- 2601416 TI - Studies on age-related functional changes in regulatory T cells and B cells involved in the autoantibody production of MRL/MpJ- +/+ mice. AB - Age-related changes in anti-DNA autoantibody production of MRL/MpJ- +/+ mice were investigated. In lipopolysaccharide (LPS)-stimulated cultures, spleen cells of the mice showed an age-related, marked increase in the ability to produce IgG class of the autoantibody after the age of 12 months, while they showed a tendency to decrease with age in the production of IgM class of the autoantibody. Serum levels of anti-DNA autoantibodies rose markedly in the IgG autoantibody but not in the IgM autoantibody after 12 months of age, which is well consistent with the observation in the LPS-stimulated cultures. T cell-depleted spleen cells, however, showed only a small increase with age in the IgG autoantibody productive ability. These results suggest that the age-associated increase in the IgG autoantibody production in the mice is under T-cell control. Age-associated changes in suppressor capacity in spleen cells of the mice were also investigated. Suppressive activity of the cells stimulated by 2-day incubation with concanavalin A (Con A) showed a clear increase as the donor age advanced, when assayed on the LPS-stimulated anti-DNA autoantibody production in vitro. The results indicate that, in MRL/MpJ-+/+ mice, suppressor capacity does not decline with age and is not related as a cause to the autoantibody production. PMID- 2601418 TI - 15 esthetic solutions to dental problems. PMID- 2601417 TI - A mathematical model of physiological processes and its application to the study of aging. AB - The behavior of a physiological system which, after displacement, returns by homeostatic mechanisms to its original condition can be described by a simple differential equation in which the "recovery time" is a parameter. Two such systems, which influence one another, can be linked mathematically by the use of "coupling" or "feedback" coefficients. These concepts are the basis for many mathematical models of physiological behavior, and we describe the general nature of such models. Next, we introduce the concept of a "fatal limit" for the displacement of a physiological system, and show how measures of such limits can be included in mathematical models. We show how the numerical values of such limits depend on the values of other system parameters, i.e., recovery times and coupling coefficients, and suggest ways of measuring all these parameters experimentally, for example by monitoring changes induced by X-irradiation. Next, we discuss age-related changes in these parameters, and show how the parameters of mortality statistics, such as the famous Gompertz parameters, can be derived from experimentally measurable changes. Concepts of onset-of-aging, critical or fatal limits, equilibrium value (homeostasis), recovery times and coupling constants are involved. Illustrations are given using published data from mouse and rat populations. We believe that this method of deriving survival patterns from model that is experimentally testable is unique. PMID- 2601419 TI - Disability insurance: planning for the unexpected. PMID- 2601420 TI - Work and play: a motivating mix. PMID- 2601421 TI - Small labs: making the most of limited space. PMID- 2601422 TI - Cost-efficient design boasts pre-fabricated flame retardant walls. PMID- 2601424 TI - When small is beautiful. PMID- 2601423 TI - Organized orientation for new employees. PMID- 2601425 TI - Visual stimuli. PMID- 2601427 TI - Lab on wheels. PMID- 2601426 TI - Resolving interpersonal conflicts. PMID- 2601428 TI - Measurement of perception threshold to an electric stimulus using a phase sensitive technique in normal and diabetic subjects. AB - To evaluate the functional state of peripheral sensitivity we measured the perception threshold to an electrical stimulus applied deeply at the level of the lower limbs in both diabetic and nondiabetic patients. The data were obtained using a phase-sensitive technique with a sinusoidal applied voltage at 1592 Hz. The test signal applied through needle electrodes was monitored using a current to-voltage convertor, the current being considered to have two components, one resistive (IR) in phase with the voltage V across the electrodes, and the other capacitive (IC) 90 degrees out of phase. A significantly (p less than 0.001) higher perception threshold was found in diabetic patients than in nondiabetic subjects with all three electrical variables measured: IR, IC and V. PMID- 2601429 TI - Signal preprocessing system for the small intestinal electromyogram. AB - The intestinal EMG obtained from chronically implanted electrodes in canine preparations provides for the evaluation of intestinal motor activity and its control. The basic electrical rhythm (BER) and spike components on the EMG signal provide evidence of control activity and a measure of contraction intensity, respectively. A hardware system is presented in which these two components are separated by filters and the contraction spikes counted in fixed epochs to yield a contraction spike per unit time record against time. The signal is also available in parallel binary form at the end of each epoch, together with a data ready signal for direct acquisition by computer. Tests of system performance and operating protocols are given. The preprocessor is used as a fast front end to a digital signal processing system specifically built for intestinal EMG analyses. PMID- 2601430 TI - Method for EMG conduction velocity estimation which accounts for input and output noise. AB - A new technique is derived for estimating the conduction velocity of muscle fibre action potentials from surface EMG recordings in humans. The method is based on system identification and extends previous such methods by explicitly accounting for additive noise at the output as well as at the input. Experimental and simulation results demonstrate that at moderate noise levels the new method yields estimates comparable to those obtained with previous methods. However, simulation studies show that the new method should be particularly valuable at high noise levels, where it should provide much better estimates than previous techniques provided that an adequate representation of the noise is available. PMID- 2601431 TI - Vibration technique for indirect measurement of diastolic arterial pressure in human fingers. AB - Diastolic pressure Pd was indirectly measured by vibrating a finger artery with a 10 Hz sinusoidal pressure variation during a gradual increase (or decrease) in occlusive cuff pressure Pc. Pulsatile arterial volume changes on which sinusoidal variations are superimposed were detected by a transmitted infra-red photoelectric plethysmograph (TIPP). It is known that volume change in an artery shows a maximum amplitude at the transmural pressure Pt level equal to 0 mm Hg due to the nonlinear viscoelastic properties of the arterial wall. For the same reason, the amplitude of the sinusoidal volume variation reached its maximum at the end-diastolic phase, when Pc was controlled to be exactly equal to Pd. The indirect Pd values determined from Pc were compared with those simultaneously measured by a direct method in rabbit forelegs and by the volume-compensation method in human fingers. Using the principle of the volume oscillometric method systolic and mean pressures were also determined by this system. PMID- 2601432 TI - Automatisation of the single-breath nitrogen washout test. AB - The paper presents a computer-based system for performance and analysis of the single-breath nitrogen washout test (Sb-N2 test). A pneumotachometer and a rapid gas analyser are used for volume flow rate and nitrogen fraction measurements. The data are acquired and analysed by a PDP-11/34 computer. Several sources of measurement errors are considered. An algorithm is proposed to reduce errors in flow measurements due to viscosity variation in respired air. The algorithm for closing volume (CV) detection and calculation of other Sb-N2 parameters is developed from 50 tracings of 18 subjects. The CV is obtained by an iterative linear fitting of the later half of the Sb-N2 curve. Comparisons between computer and hand measurements of three trained readers show good correlations (r = 0.87, 0.93, 0.91). The variability of computer CV measurements was comparable with that of the hand reader with the lowest variance. The coefficient of variation of residual volume and slope of alveolar plateau measurements are apparently reduced. The results demonstrate the adequacy and convenience of using the computer to analyse the Sb-N2 test and indicate that the automation allows for reduction of experimental errors and of test parameter variabilities. PMID- 2601433 TI - Measurement of transcellular fluid shift during haemodialysis. Part 1. Method. AB - A method is presented to measure transcellular fluid shifts during haemodialysis based on a simplified model of the electrical admittance of biological tissues. It allows for the measurement of intracellular and extracellular conductivities and their ratios. The method is noninvasive, clean and harmless, and can be easily computerised in order to be performed continuously. A typical example is given of a recording during haemodialysis. PMID- 2601434 TI - Measurement of transcellular fluid shift during haemodialysis. Part 2. In vitro and clinical evaluation. AB - A method to measure intra- and extracellular conductivity is evaluated. In vitro experiments show that these two variables can be measured separately. The conductivity appears to depend on the concentration and fluid volume of the compartment concerned. In vitro variation of the intracellular volume of blood by dilution and by shrinking and swelling of blood cells is detectable by this method. In vivo too the method seems to detect intra- and extracellular fluid volumes separately. The course of these two variables during different strategies of haemodialysis is determined. PMID- 2601435 TI - Adaptive numerical smoothing: an efficient method of conditioning physiological signals. AB - The main aim of the paper is to present a method of reducing the number of necessary operations in the process of numerically smoothing digitised signals, together with increasing the quality of smoothing, using suggestions which are new in the technique of numerical smoothing. The first suggestion consists of an analytical description of the smoothing process and the representation of the input mixture and undergoing smoothing signals by a series of sinc functions. The second proposal consists of using adaptive smoothing, i.e. smoothing with varying step and with some special means for increasing the quality of smoothing. These procedures must be calculated together with the processing and this procedure causes a small delay in the output signal. The approach presented is a deterministic one, i.e. the information about all instantaneous values of the input mixture is used instead of an a priori average information about disturbances. Attention is directed towards disturbances which are associated with physiological signals such as pressure, flow and electrocardiogram waveforms. The paper contains the basic theory and some experimental results which demonstrate the potential of adaptive smoothing. PMID- 2601437 TI - Effect of metal-framed spectacles on microwave radiation hazards to the eye of humans. AB - A novel measurement technique using a monopole antenna probe has been applied to a full-size, image-plane type model of a human to determine the microwave fields near the eyes and to evaluate the effect of scattering structures, such as metal framed spectacles, on those fields. The measurement technique relies on a 'subtraction' technique to determine the changes in fields when a scattering structure is introduced, and allows a large number of measurements to be performed in a relatively short space of time and with a high degree of accuracy. Investigations conducted in an anechoic chamber yield angles of incidence, test frequencies and wave polarisation values that give details of shielding, enhancement and depolarisation effects due to this particular scattering structure that appeared not to have been previously studied. It has been found that the introduction of a pair of metal-framed spectacles can, in certain cases, cause an increase in field levels by up to approximately 20 dB, a significant perturbation of the incident microwave field which should be accounted for in the setting of safety standards relating to acceptable levels of incident power. PMID- 2601436 TI - Postural stability in stroke patients: vectorial expression of asymmetry, sway activity and relative sequence of reactive forces. AB - Bilateral force measurements on the supporting limbs in postural sway while standing still were made to evaluate post-cerebral-vascular accident (CVA) patients during rehabilitation. Normal subjects of the same age group were tested as controls. From the force tracings obtained, three oscillation frequencies were identified, with orders of magnitudes of 7, 1 and 0.1 Hz, respectively, of which the middle frequency, i.e. that corresponding to 1 Hz, was selected for subsequent processing and analysis. These included the determination of relative sequence of the force vectors on both feet and evaluation of timings and amplitudes of the waveforms. Weight-bearing imbalance was defined in the vertical direction to express the difference between the average forces supported by each of the legs. In the horizontal plane, two parameters were defined: sway total activity (SA), to represent the vector summation of the absolute values of the horizontal force components acting on both legs; and asymmetry (ASYM) to express the difference in activities between the two legs. The results presented disclose the reactive force patterns acting on each of the legs of post-CVA hemiplegic individuals, in comparison with normal individuals. Although these forces were shown to act synchronously on both legs, they appeared to be asymmetrical in nature, with a typical vectorial pattern for every individual, which generally differed from that of normal subjects. Sway activity was found to be significantly higher in hemiplegics compared with the normal controls. PMID- 2601438 TI - Weak reflection of ultrasound by elements arranged in the steps of a one dimensional random walk, with reference to backscatter by blood. AB - Blood backscatters ultrasound primarily because the erythrocytes (red blood corpuscles) have a specific acoustic impedance slightly different from that of the surrounding plasma. In an attempt to explain some of the main results concerning such scatter, a one-dimensional model is set up and analysed. The results computed from it are in qualitative agreement with, and contribute a partial explanation of, the variation of reflection coefficient with erythrocyte concentration and the noise in the backscattered signal. PMID- 2601439 TI - New prosthesis with low airflow resistance for voice restoration following total laryngectomy. PMID- 2601440 TI - Sampling technique for an ultrasound Doppler system. PMID- 2601441 TI - Safe device for delivery of aversive stimuli in behaviour therapy. PMID- 2601442 TI - Baseband transmit and receive processors for two-channel PWM telemetry. PMID- 2601443 TI - Bottom-up approach to the ECG pattern-recognition problem. AB - A bottom-up approach to the recognition problem in ECG waveforms is presented in the paper. This approach is based on the assumption that ECG waveforms are composite entities that can be decomposed into other simpler entities, these into other simpler ones etc., until peak patterns and segment patterns are obtained. The peak patterns and the segment patterns are considered primitive (nondecomposable) patterns. The recognition is achieved by first recognising the primitive patterns and then recognising the (higher) ECG patterns using a bottom up procedure. PMID- 2601444 TI - Dual-pathway model of the human vestibulo-ocular reflex. AB - The purpose of the study was to investigate, evaluate and refine an existing dual pathway VOR model by comparing the model responses with the responses of human subjects. Based on data of subjects' VOR responses, the physiological parameters and some gain constants in a dual-pathway model were adjusted to suit the human VOR data. As a result, the improved model can produce and exhibit the fundamental nystagmus patterns of human VOR responses to the head motions around a vertical axis for a wide range of frequencies and magnitudes. It was found that there is good agreement on quantitative analysis between the outcome of human VOR responses and the model output. Also, it was found that the quantitative analysis of slow-phase eye-movement data confirmed the previously published results. PMID- 2601445 TI - Microprocessor-controlled vector scan display system for generation of real-time visual stimuli. AB - The paper describes a low-cost, versatile, widely applicable digital display system in which a high-resolution, high-intensity display unit is driven by a real-time vector scan controller. The actual online display control of this device is preceded by an offline software stimulus-frame editor, designed to create and support a library of stimulus patterns (standard frames without any timing information and without any referencing to a special display co-ordinate system). The display times can be set individually for each single frame (containing at maximum 1023 pixels) with relative ease. Display frequency is set to 1 kHz. Writing time per pixel is less than 1 microsecond. A graphic display system like the one presented in this paper can be applied to generate a variety of real-time optical stimuli, such as intensity modulation of single spots or distinct display areas, abrupt displacements of a certain pattern, continuous movement or onset and offset of steady motion of a pattern. PMID- 2601446 TI - Quantitative analysis of the insulating effect of silicone oil on the electroretinogram. AB - A model of the ERG focusing on the insulation effect of silicone oil replacing the vitreous was used to quantify the ERG. The electrical properties of the structures of the eye, the frequency content of the ERG and the percentage of the silicone oil along with the remaining vitreous were incorporated in the model. The result was that it was not until at least 50 per cent of the vitreous was replaced with silicone oil that there was a small reduction in the ERG. As more silicone oil was put into the vitreous cavity the ERG became smaller. If the replacement were large leaving a layer of vitreous 0.24 mm thick, little ERG would be measured even if the retina were functional. PMID- 2601447 TI - Model of respiratory sinus arrhythmia in man. AB - The first section of the model delineates the parasympathetic signal as a function of the interaction between the respiratory and the vagal neurones of the common brainstem network. The second section is a version of Chess and Calaresu's description of the vagus/heart period system in the sympathetically blocked cat. The sympathetic influence is introduced in the third section, taking into account the autonomic effects on the transmembrane potential of the sinoatrial pacemaker as found in the rabbit. The model was implemented on a dedicated analogue computer with an accuracy of 1 per cent. The concordance between the analogue and the breathing/respiratory sinus arrhythmia (RSA) system in humans was studied using simulated respiratory signals. The results confirm the central origin of the RSA as a meaningful modelling premise and indicate the dependence of the RSA amplitude on the operating point of the vagus. PMID- 2601448 TI - Mathematical model for interpretation of Doppler velocity waveform indices. AB - Various empirical indices such as the pulsatility index (PI) are widely used for quantitative analysis of Doppler ultrasound velocity waveforms. The physical interpretation of these indices was studied using a mathematical model. Although the method has more general applicability, this particular study was concerned with the umbilical-placental circulation. A lumped element electrical circuit equivalent was used, with each arterial branch represented by a resistor and a capacitor. The placental villous bed was modelled by a two-step parallel branching structure. Placental vascular disease was modelled either as obliteration of a fraction of the terminal branches, or as a fractional decrease in the radius of the vessels. The main features of both normal and abnormal umbilical artery waveforms can be reproduced by this simple model. Theoretical relationships between the velocity waveform indices and the lumped resistances and capacitance of the system were obtained for different input pressure functions. Over a wide range of physically reasonable conditions, the umbilical artery PI is approximately proportional to the ratio of the placental resistance to the umbilical artery resistance. The PI also depends on the pulsatility of the input pressure waveform. The Fourier pulsatility index was evaluated for an arbitrary pressure function, and shown to behave like (PI)2 for the umbilical artery waveform. PMID- 2601449 TI - Principles and appraisal of combined images in NMR. AB - The interpretation of NMR images at Aberdeen is most often performed by the individual study of the proton density, difference, inversion recovery and T1 image. This report investigates the usefulness of presenting the information from a pair of images, in this instance the T1 and proton density images, in a single composite image. Information from the two images is combined such that the values from one image are represented by a change in hue (colour), and the values from the other by a change in luminance (intensity). To test the advantages of such combined images, a trial was run using a selection of prediagnosed abnormal brain scans. The information perceived as hue and luminance in the combined images was compared with that from separate conventional monochrome proton density and T1 images. Medical and nonmedical users were told the final diagnosis and were asked whether it was possible to see more, less, or the same information with regard to clinically relevant details in the structure of the abnormality and the image as whole. The results have revealed that for the majority of cases the combined image format can effectively represent the information normally contained in both the monochrome proton density and T1 images--thus speeding up the image viewing process. PMID- 2601450 TI - Improved photomultiplier tube for positron emission tomography. AB - The paper describes an investigation in which it is shown that small positive voltage pulses applied to an external conductor placed against the photocathode of a photomultiplier tube can be used to switch the photocathode completely off for the duration of the pulses. This suggests that a photomultiplier tube with a multisegment photocathode can be constructed, the individual cathode segments of which can be switched off independently by means of such pulses. A theoretical explanation for the effect is provided with the aid of a simple circuit model for the photocathode. Analysis of the model also shows that it is possible to identify the particular cathode segment in which a photon is detected when a pulse is recorded at the phototube's anode. A phototube with these characteristics can have important implications for positron emission tomography, as it can provide improved spatial resolution, simultaneous multislice capability and the ability to eliminate distortion due to dead-time effects at high count rates. PMID- 2601451 TI - Simultaneous measurement of surface EMG and movements for clinical use. AB - A system for simultaneous measurement of surface EMG, joint movement and temporal parameters of gait has been developed for clinical use. Some design constraints, imposed by the clinical situation, are indicated. Multiple cycles of movement are recorded and averaged patterns of muscle activation and joint movements are determined. Data processing runs concurrently with data acquisition, so that the results are available for clinical interpretation immediately after the measurement. Instrumentation, signal processing and software are described and some examples of application of the system for evaluation of therapies and functional aids are presented. It is proposed that clinically relevant quantitative information can be obtained by comparison of different recordings of the individual patient rather than comparison with patterns found with normal subjects. PMID- 2601452 TI - Better quantification of neonatal respiratory sinus arrhythmia--progress by modelling and model-related physiological examinations. AB - A large interindividual variability of parameters quantifying respiratory sinus arrhythmia were found in a well defined group of healthy neonates during constant conditions of examination. Reasons for this can be found by means of a mathematical model which is based on physiological data. The results indicate sharp inconsistencies in the transfer function between respiratory movements and resulting respiratory sinus arrhythmia and are dependent on a relative frequency unit fN (ratio of mean respiration rate to mean heart rate). The values of the coherence (as a function of this relative frequency unit) between respiratory movements and heart rate are also distinguished by a systematic decrease from lower to higher fN values (fN = 0.1-0.5) and inconsistencies in modelling as well as in physiological examinations. The reasons for both effects can be demonstrated. The study is the basis of a new qualitative step of quantification of respiratory sinus arrhythmia in neonates by power spectral and coherence analyses. PMID- 2601453 TI - Method to localise myocardial infarction using magnetocardiography: simulation studies. AB - The work presents a method for localising regions of myocardial infarction (MI) using magnetocardiography, which is validated by simulation techniques. We have verified that the first two principal components of magnetocardiographic signals obtained from torso mapping within a normal group are very similar even in experimental measurements. So, if we have the temporal eigenvectors of a normal group, these can be used as an orthonormal basis for estimating the signals of a patient being tested. Analysis of the residual signals using singular value decomposition (SVD) allows the localisation of regions of MI. Comparisons are made with a similar method which uses spatial eigenvectors as its basis. It is shown that our approach is able to localise the equivalent current dipoles which generate MI even when they are not orthogonal to the spatial eigenvectors. PMID- 2601454 TI - Estimation of elastic properties in the urethral flow controlling zone by signal analysis of urodynamic pressure/flow data. AB - When urethral flow is treated as a lossless flow through an elastic tube, the relationship between the detrusor pressure and the urinary flow can be related to the elasticity of the flow-controlling zone of the urethra. A recent analytical method of describing urethral elasticity is implemented on a computer. The function p(Q) = pmo + LmQm is fitted to the recorded pressure/flow data. p(Q) is the detrusor pressure, Q the flow and pmo, m and Lm parameters. The elastic properties are then obtained as p(A) = pmo + KnAn, where p(A) is the static pressure, A the cross-sectional area of the flow-controlling zone and n and Kn calculated parameters. The urodynamic methods used and the computer implementation of the analytical method are described. In obstructed and unobstructed men without neurological symptoms, the elastic properties could be estimated in 94 per cent of the micturitions. The method makes it possible to describe urethral flow properties with Griffiths' model in a standardised way and compare results obtained by different investigators. It is recommended for quantification of urethral obstruction in research and for assessment of borderline cases of obstruction in clinical practice. PMID- 2601455 TI - Electrical properties of tissues involved in the conduction of foetal ECG. PMID- 2601457 TI - Alphanumerical display module for blind people. PMID- 2601456 TI - Integration of CT images into radiotherapy treatment planning using a Commodore Amiga personal computer. PMID- 2601458 TI - Fast integer coefficient FIR filters to remove the AC interference and the high frequency noise components in biological signals. PMID- 2601459 TI - Visual stimulator using laser beam for eye-movement studies. PMID- 2601460 TI - Extended voltage clamp. PMID- 2601463 TI - Cross-sectional area measurement in collapsed tubes using the transformer principle. AB - To avoid the necessity for intraluminal catheters as used with the axial impedance method of measuring the cross-sectional area of flexible tubes independently of their shape, while retaining the advantage of an immediate electrical output, an electromagnetic method was tested. The method uses a single turn sensing coil attached to or embedded in the tube wall at the site of interest as the secondary winding of a transformer. One or more primary coils coaxial with the tube provide an alternating magnetic field parallel to the tube axis, and the resulting secondary voltage, after amplification and demodulation, is directly proportional to tube cross-sectional area. Tube pressure/area relationships measured thus were compared with those measured using both an ultrasonic imaging technique and liquid volume displacement. The method was shown to provide an accurate and relatively simple alternative to the impedance method. Various ways to fabricate tubes with or otherwise introduce the necessary sensing coil are discussed. PMID- 2601461 TI - Frequency response model of skeletal muscle: effect of perturbation level, and control strategy. AB - The frequency response model of the soleus muscle of the cat was determined as a function of various firing rate and recruitment control strategies and at various force oscillation levels. We found that the basic frequency response models of the muscle during individual force oscillations at various control strategies in which the motor unit population of the muscle was fully recruited to obtain 50 per cent and up to 100 per cent of the maximum force, either concurrently with firing rate increase or at constant firing rate, were nearly identical. The model consisted of a second-order, linear low-pass filter with double poles at 1.85 Hz and a pure time delay of 16 ms. The model resulting from only firing rate increase from the frequency of fusion of the smallest motor unit to the maximum tetanic rate of the muscle while all the motor units were continuously active was nonlinear, and depended on the force's oscillation level. This nonlinear response of the rate coding process is also identified as the source of the increased harmonic distortion in the model where the initial 50 per cent of the force was generated by fully recruiting all the motor units, and the final 50 per cent of the force was generated by firing rate increase. We concluded that the basic frequency response model of a muscle under conditions similar to voluntary contraction consists of a linear, second-order system which is robust and independent of control strategy and force perturbation level. PMID- 2601462 TI - Ag/AgCl electrode assembly for thin smooth muscle electromyography. AB - An electrode assembly for in vivo recording of the electrical activities of thin muscular layers is described. It comprises an active electrode surrounded by a ring, which avoids the recording of interfering signals. An improved technique for chlorinating the silver electrodes is presented: a partial electrolytic removal of an initial thick deposit is performed. This decreases the impedance, and lowers the ageing degradation of the electrodes in vivo. Recordings of extremely low frequency signals are allowed, whereas standard Ag/AgCl electrodes are inefficient when recording signals in the frequency domain under 0.1 Hz. The technical features which are described can be adapted to any Ag/AgCl electrode developed for in vivo measurements. PMID- 2601464 TI - Distributed computer system for capture, analysis and display of biological data. AB - A distributed real-time computer system has been developed to automate the collection, analysis and display of biological (pharmacological) data. It comprises a series of laboratory interface devices (CED 1401/1609) connected to a micro-VAX II via multiple IEEE-488 buses. The micro-VAX II is integrated to the main site computers using Ethernet running DECnet. The micro-VAX II system supports a multi-user, multipreparation and multitasking environment and it provides rapid transfer, storage, analysis and display of data. The system saves the pharmacologists from the manual analysis of their data, typically saving them four days of analysis per experiment and has improved both the quality of data detected and their subsequent analysis. Also, the development of a standard data capture procedure on common hardware along with the modular design of application software has almost quartered project development times. PMID- 2601465 TI - Quick method of measuring the furrows distribution on skin surface replicas. AB - A fast method of measuring the distribution of furrows can be obtained via the analysis of TV camera images of skin replicas. These replicas are either negative (or direct) or positive. Reflected or transmitted light is used, depending on the type of replica. Each point of the matrix (256 x 256 pixels) is digitised over 6 bits (64 levels) and treated by a personal computer (IBM AT or PC). With such an image, it is not possible to obtain significant results without eliminating noise and enhancing the furrows. Specific software is written in processor language 8086 to obtain a real time system. The distribution of skin furrows is quantified for several interesting cases such as the ageing of the skin or the effect of stress. PMID- 2601466 TI - Changes in skin potentials induced by skin compression. AB - Changes in skin potentials are known to occur upon stretching and compressing the skin. In this work the relationship between compressional force and changes was studied for forces up to 13.7 N. For a given force, a flatter compressing surface gave lower potential changes than a more curved surface. When temperature increased both changes in potential and current decreased. PMID- 2601467 TI - Noninvasive heart rate monitoring system for avian embryos based on the ballistocardiogram. AB - A noninvasive heart rate (HR) monitoring system for avian embryos has been developed based on the ballistocardiogram (BCG). The BCG was detected using a phonograph cartridge as a record of the velocity of the minute ballistic movements of the eggshell, which are generated by recoil and impact of heart contraction and blood ejection. The autocorrelation coefficients (ACCs) of the detected signal were computed to confirm whether the detected signal contained ballistic movement. An envelope of ACC was calculated by the monitoring system to measure the intervals between peaks and/or highly correlated parts in the ACC, and then the system obtained HR by measuring these intervals. To demonstrate the valid range of the detecting method, the BCGs of chickens and Japanese quail embryos of different ages were measured. The result of the experiment shows that the BCGs of chickens and quail embryos are detected fully after about two-thirds of the incubation period has passed. The monitoring system will enable us to perform long-term HR measurement for developing avian embryos up to hatching. PMID- 2601468 TI - Model study of the spread of electrotonic potential in cardiac tissue. AB - This model study describes the electrotonic response of a cable model of cardiac tissue stimulated at one point. The stimulus is applied intracellularly in the form of a 2 ms pulse of current of near threshold amplitude. The attenuation of the electrotonic potential with distance and its mode of propagation along the cable are compared for equivalent passive, continuous and discontinuous cables. The three structures have the same basic physical and electrical characteristic and they differ either with respect to being active or passive or to the presence or absence of intercellular gap junctions. In the continuous cable a just subthreshold stimulus produces a local active response which propagates more slowly and is attenuated less rapidly with distance than in a passive cable. The spatial decrement of the local response in a discontinuous cable is faster than in a continuous cable of equal average resistivity. It is suggested that the larger time constant of the foot of the action potential observed in the longitudinal direction in cardiac muscle could be due in part to the electrotonic spread of the local response from the site of stimulation. PMID- 2601469 TI - Incremental network analogue model of the coronary artery. AB - From Newton's equation and the continuity equation, an equivalent analogue circuit model can be derived for each small segment of the coronary arteries. Sapoznikov divided the coronary artery tree into 116 segments. By replacing each segment with its analogue circuit model, a final incremental network model was derived. The model was tested using typical physical parameters under normal conditions, as well as in the presence of coronary artery stenosis. In the case of stenosis, the arteriolar flow with and without autoregulation were compared. The model shows good agreement with the reported effects of stenoses and heart rate on coronary blood flow. PMID- 2601470 TI - New noninvasive piezoelectric transducer for recording of respiration, heart rate and body movements. PMID- 2601471 TI - Transthoracic resistance changes during cardiac defibrillation. PMID- 2601472 TI - Testing of heat exchanging capacity and effect of the subject's position on thermal entrainment in a water bath stimulator. PMID- 2601473 TI - Combined water bath and rocking tilt table stimulator to test autonomic function by a thermal and postural entrainment method. PMID- 2601474 TI - Novel FIFO computer interface for gamma cameras. PMID- 2601475 TI - Experimental determination of the frequency response characteristics of physiological pressure measurement systems. PMID- 2601476 TI - Tests on a shocking device--the stun gun. PMID- 2601477 TI - [Systemic vasculitis as a cause of fever of unknown origin]. AB - A prospective clinical study (1974-1988) was carried out in 33 patients with several types of systemic vasculitis (SV) presenting as fever of unknown origin (FUO) according to the 1961 Petersdorf and Beeson's criteria. Histological confirmation, either from biopsy or necropsy, was available in all cases. The types of SV with FUO were: panarteritis nodosa (PAN) (14 cases), giant cell arteritis (GCA) (13 cases), and overlapping polyangiitic syndrome (OPS) (6 cases). In PAN, the clinical features associated with fever at the onset of the disease were remarkably nonspecific: constitutional symptoms (85%), arthromyalgia (50%), nonspecific abdominal pain (28%), and irritative cough (28%). In the whole course of the cases of GCA a significantly smaller frequency of presentation of local arterial symptoms and polymyalgia rheumatica (p less than 0.01) was found in the subgroup of patients with FUO than in those without it. As regard laboratory data, a higher increase of serum alkaline phosphatase (p less than 0.05) was found in the cases of PAN and OPS with FUO. Striated muscle biopsy and arteriography were the most useful investigations in the diagnosis of PAN. The study that gave the diagnosis in the cases of GCA was temporal artery biopsy. PMID- 2601478 TI - [Evidence of infection by type 2 (HIV 2) human immunodeficiency virus in heroin addicts in Barcelona]. AB - The presence of antibodies against human immunodeficiency virus type 2 (HIV-2) was retrospectively investigated in serum samples from 433 parenteral drug abusers from Barcelona. A third generation ELISA was used for the initial screening of sera, and a specific western blot technique for the definitive confirmation of the results. The presence of anti-HIV-2 was demonstrated in 9 samples (prevalence 2.1%). All of them belonged to patients also infected with HIV-1. The 9 cases reported here are the first seropositive patients for HIV-2 described in native individuals from this country. PMID- 2601479 TI - [Quality of life after liver transplant]. AB - Hepatic transplant has recently undergone ostensible changes in post operative mortality. The present study investigates whether this improvement in survival is associated with a subjective and objective improvement in quality of life. Nineteen patients were evaluated preoperatively and/or postoperatively with a questionnaire (Nottingham Health Profile). The results showed a remarkable improvement in the quality of life of these patients, which became more marked after three months. The readaptation to work was good, considering the current state of our society. The mean yearly hospital stay was 12 days, distributed in three admissions mainly to perform hepatic biopsy. PMID- 2601480 TI - [Meningoencephalomyelitis caused by Borrelia burgdorferi: a case without epidemiologic history or chronic migratory erythema]. AB - A patient is reported with meningoencephalomyelitis with polyradiculitis caused by Borrelia burgdorferi infection. Neurological features developed without previously known tick bite nor the characteristic skin lesion, chronic migratory erythema (CME). The vector of the disease (the tick Ixodes ricinus) exists in Spain, but only one case of meningopolyradiculitis with CME has been reported in Asturias. Our case stresses that B. burgdorferi infection should be suspected in cases of meningoencephalomyelitis or meningopolyradiculitis even without previous skin or joint lesion. PMID- 2601482 TI - [Tuberculous cerebral abscess and acquired immunodeficiency syndrome]. PMID- 2601481 TI - [A 68-year-old male with fever, pulmonary interstitial pattern and hepatic dysfunction]. PMID- 2601483 TI - [Hyperlipidemia and ischemic ictus. The need for population studies]. PMID- 2601484 TI - [Are biochemical parameters useful as activity indicators in inflammatory intestinal disease?]. PMID- 2601485 TI - [The Kasabach-Merrit syndrome treated with aminocaproic acid]. PMID- 2601486 TI - [Acute recurrent pancreatitis caused by estrogens]. PMID- 2601487 TI - [Carcinoma of unknown origin]. PMID- 2601488 TI - [Future emergency departments: the city emergency center or a qualified unit for the severely ill and injured]. PMID- 2601489 TI - [Minimal surgery in Crohn disease]. PMID- 2601490 TI - [Where are the suitable sites for intramuscular injections?]. PMID- 2601491 TI - [AD drops caused adverse effects in 6 cases]. PMID- 2601492 TI - [Amalgam disease and dental personnel]. PMID- 2601493 TI - [Lead in bones--a new dosimetric measurement in environmental medicine]. PMID- 2601494 TI - [Healthy persons are classified as hypertensive due to faulty equipment for blood pressure determination]. PMID- 2601495 TI - [General views on children with MBD]. PMID- 2601496 TI - [Early retirement can be often predicted--a prospective study]. PMID- 2601497 TI - [Musculoskeletal anaerobic infections]. PMID- 2601498 TI - [How important are psychosocial factors in musculoskeletal disorders?]. PMID- 2601499 TI - [Medical ethics in the everyday practice of the pediatrician--is the patient's rights compromised without good reason?]. PMID- 2601500 TI - [Private practice in psychiatry: which abusers can be treated in private ambulatory care?]. PMID- 2601501 TI - [Female physicians feel inferior to their male colleagues]. PMID- 2601502 TI - [An alarming increase in the prescription of antibiotics]. PMID- 2601503 TI - [All adopted children should be HIV tested]. PMID- 2601504 TI - [Does the high selenium intake of the population of Lappland mean a lower risk of cancer?]. PMID- 2601505 TI - [The automatic implantable defibrillator is an established preventive method against sudden cardiac death]. PMID- 2601506 TI - [The scoliometer is an effective diagnostic aid]. PMID- 2601507 TI - [Subcutaneous implantable injection sites for a better quality of life of children with cancer]. PMID- 2601508 TI - [Eradicate endemic gonorrhea in Stockholm--an annual report]. PMID- 2601509 TI - [Alveolitis occurs even during childhood, and the causes can be found in the home environment]. PMID- 2601511 TI - [What is most important in risk evaluation: probability or consistency?]. PMID- 2601510 TI - [Persistent trophoblastic tissue following surgery of a tubal pregnancy]. PMID- 2601512 TI - [Food and health]. PMID- 2601513 TI - [Cessation of smoking during pregnancy can cause heavy weight gain]. PMID- 2601515 TI - [Clinical methods of general medicine]. PMID- 2601516 TI - [When can treatment be withdrawn or interrupted? Ethical problems are increasingly burning questions]. PMID- 2601514 TI - [Recommendations from a group of experts: drug therapy of the climacteric syndrome]. PMID- 2601517 TI - [New rules for clinical trials in the USA will introduce new drugs on the market earlier]. PMID- 2601518 TI - [Schizophrenia and a new view on handicaps--make municipalities assume their responsibility]. PMID- 2601519 TI - [Everyday health care in Leningrad. Old methods and a shortage of money]. PMID- 2601520 TI - [Active care of uremia]. PMID- 2601521 TI - [Prolonged or early use of oral contraceptives--which one is the greatest risk for the development of breast cancer?]. PMID- 2601522 TI - [Do patients with uremia receive sufficient health care? Varying estimations of the need for dialysis]. PMID- 2601523 TI - [Food and health. Can fasting with water or glucose influence the biological clock?]. PMID- 2601524 TI - [An overview of risk comparisons]. PMID- 2601525 TI - [A foreign body in the respiratory tract--a diagnostic problem at Christmas time]. PMID- 2601526 TI - [Manual and stapler bronchial anastomosis]. PMID- 2601527 TI - [Stapler and manual bronchial anastomosis--results of a consecutive trial series]. AB - After lobectomy and pneumonectomy in experimental evaluations stapled bronchial closures showed the lowest incidence of inflammatory reaction and the highest strength determined by leakage pressure compared with other suture material. A total of 233 lung resections-performed at Surgical University Clinic Koln Lindenthal and the Clinic for General and Abdominal Surgery of the Johannes Gutenberg-Universitat Mainz--were reviewed. Mechanical stapling reduced the rate of bronchopleural fistulas to 2.0% compared with 7.1% after manual suturing. In parallel, mortality related to bronchial stump leakage decreased to 0.7%. Main advantages of bronchial closure with staplers are the simplicity of their use, the speed and the uniformity of the closure. Thereby stapling devices are valuable completions in pulmonary surgery. PMID- 2601528 TI - [Erectile dysfunction following pelvic fracture and pelvic trauma]. AB - In the course of this research a questionnaire was submitted to 209 male patients who had been treated in the surgical university clinic of Erlangen between 1976 and 1985, in order to get knowledge about possible complications in the form of erectile non-functioning. 29 of these patients had died in the meanwhile, 32 had moved to an unknown address. Among the other 148, 86 were willing to give some information. 44% of these people turned out to be suffering from an impotentia coeundi. Furthermore, we were able to prove that 40% of those patients for whom a large haematoma of the pelvis had been diagnosed were impotent. Finally, 73% of the patients who had additionally suffered an injury of the urogenital canal turned out to be impotent. On closer examination of the urogenital side-effect case of rupture of the bladder and as much as 87.5% in the case of lesions of the urethra. In connection with the urethra lesions reference is made to the controversial discussion about their therapy, with dichronous recanalling clearly being given preference as it involves considerably fewer complications compared to primary recanalling. PMID- 2601529 TI - [Primary non-Hodgkin's lymphoma of the stomach]. AB - Between 1980 and 1987 a total of 17 patients were operated upon in curative intention of the Non-Hodgkin-Lymphoma of the stomach at our surgical department. Ten of these patients were within Ann-Arbor-Stage I, four within stage II/1 and the other three within stage II/2. In six cases we found low-malignant and in the other 11 cases high-malignant tumors. One patient died postoperatively after a myocardial infarction, one female died four months postoperatively in spite of chemotherapy of the disease. 15 patients (94%) are still alive today without any new symptoms of the disease, within a median average observation time of 40.6 months. PMID- 2601530 TI - [Effect of surgical timing and circulatory stability of various femoral shaft sections on fracture healing]. AB - Between 1976 and 1986 in our clinic 273 patients aged 3 to 93 years underwent operation of the femur shaft because of fracture. 79% had multiple injuries. 254 with 269 fractures survived. 52 out of them had open fractures. All operated fractures were analysed concerning fracture type, fracture localization and timing of operation. We saw 36 complications (13.4%), 13 bone infections (4.8) and 23 non-unions (8.6%). 40% of the patients were operated immediately, 23.4% within the first week. Early operation of closed fracture showed 11.5% complications, operation within the first week showed 14% complications, and delayed operation only 5.7% complications. We saw 7 infections (3.5%) and 20 non unions (9.9%) after 202 fixations with AO-plates, and 2 infections (4.3%) and one non-union (2.2%) after 46 Kuntscher-nailings. Multi-fragment fractures showed considerably more complications (15%) than other types. 23 fractures in the transition from the middle to the distal third had the highest complication rate (13% infections and 21% non-unions) followed by 115 fractures in middle part with 4.3% infections and 9.6% non-unions. Fixation of multiple-fragment fractures in the transition from the middle to the distal third with AO-plates had the worst rate of non-unions of all (4 out of 16). The reasons for the different complication rates are discussed. The striking increase of complications from proximal to distal shaft regions is explained by different blood flow alterations in femur diaphysis found in former experiments. PMID- 2601531 TI - [Postoperative results and follow-up of thoracic aortic diseases using magnetic resonance tomography]. AB - Operations of the thoracic aorta for aneurysms, dissections, or congenital malformations may lead to early or late complications. Therefore, postoperative control for documentation of the surgical results, for exclusion of early changes and for comparison with later controls is mandatory. To demonstrate that magnetic resonance imaging (MRI), which we already had used with good results for preoperative studies is also able to detect postoperative abnormalities, we examined 30 patients with thoracic aortic disease (20 male, 10 female, mean age 53 +/- 13.7 years) with this diagnostic tool. There were 19 arteriosclerotic aneurysms, 10 dissections, and one aortic tumor. With MRI it was possible in all patients to visualize the results of the surgical treatment postoperatively. Early postoperative complications could be excluded, or demonstrated in one case of a retrograde aortic dissection or a hematopericardium. These pathological findings could also be shown by arterial digital subtraction angiography or echocardiography. Using MRI for follow-up of aortic dissections, the development of an aneurysm of the aortic root in a Marfan-patient could be detected. In all these patients, it was possible to differentiate true and false lumen and to detect the origin of major side branches. The diagnostic advantages of MRI, which we compared with other imaging methods, as echocardiography, computed tomography or angiography are that postoperative complications of thoracic aortic aneurysm surgery can be reliably detected and visualized in 3 different planes. Non invasiveness, the omission of ionizing radiation and no risk of contrast media application underline that magnetical resonance imaging is an ideal method for follow-up after operation of the thoracic aorta. PMID- 2601532 TI - Surgical technique in prolapse of the rectum. PMID- 2601533 TI - Acoustic characteristics of speech following uvulopalatopharyngoplasty. AB - Selective uvulopalatopharyngoplasty has resulted in the improved management of sleep apnea; however, the effect of the surgery on speech has not been systematically evaluated. In this study, the speaking fundamental frequency, reading rate, and first and second formants of the vowels of four patients were measured acoustically presurgically and postsurgically. The results indicate that the length of time needed to read a passage was reduced in all four patients 2 weeks following surgery compared to the presurgical duration. In addition, the second formant of nine vowels studied was lower postsurgically. No changes in speaking fundamental frequency were found in three of the four patients; in the fourth, the speaking fundamental frequency was lower by approximately one semitone. Based on the reduced reading rates from the presurgical to the postsurgical conditions, changes in respiratory parameters in addition to vocal tract parameters warrant assessment when evaluating the speech of individuals prior to and following uvulopalatopharyngoplasty. PMID- 2601534 TI - Management of osteomyelitis of the skull base. AB - Osteomyelitis of the skull base is the most severe form of malignant otitis externa. As a result of having treated 13 patients with skull base osteomyelitis over a 4-year period, we have developed a method of staging and monitoring this malady using gallium and technetium scanning techniques. Stage I is localized to soft tissues, stage II is limited osteomyelitis, and stage III represents extensive skull base osteomyelitis. All stages are treated with appropriate antipseudomonal antibiotics. The duration of therapy depends upon the clearing of inflammation as shown on the gallium scan. Each case must be looked at independently and not subjected to an arbitrary treatment protocol. PMID- 2601535 TI - Simultaneous auditory stimuli shorten saccade latencies. AB - Eye movement responses induced by vestibular, smooth pursuit, and optokinetic stimulation are largely dependent on the velocity of the stimulus. Saccade latencies, on the other hand, are a function of the anatomic and physiologic components of the reflex. By producing an audible click simultaneously with the movement of a visual target used to stimulate a saccadic eye movement, the saccade latency is significantly shortened. This does not appear to be due to alerting. It is probably due to an auditory input to the superior colliculus which decreased threshold for initiating a saccadic eye movement. Twenty normal participants were tested with or without the click stimulus. Latencies were significantly shorter when the click stimulus was presented simultaneously with the eye movement. The anatomic pathways in this reflex are reviewed in the presentation. This study provides further information on sensory interaction in saccade reflexes and emphasizes the need to control stimulus conditions during saccade testing. PMID- 2601536 TI - Safety of total thyroidectomy: review of 100 consecutive cases. AB - During a 6-year period (June 1982 to June 1988), 100 consecutive total thyroidectomies were performed at Mount Sinai Hospital, University of Toronto, for benign and malignant disease. There were five permanent complications: one deliberate sacrifice of the recurrent laryngeal nerve and four cases of persistent hypoparathyroidism. Four of these five complications occurred in extracapsular carcinoma and resulted from oncologic wide-field resection and/or deliberate sacrifice. One patient with benign disease suffered initially transient hypoparathyroidism which has now become permanent. Interestingly, two patients actually underwent deliberate sacrifice of a recurrent laryngeal nerve; one patient has made a surprising recovery at 16 months postoperative and now has full vocal cord mobility. Our experience suggests that the morbidity of total thyroidectomy relates primarily to the stage of malignancy and extracapsular extension, necessitating en bloc excision accompanied by additional lymph node dissection. The low incidence of permanent complications in benign thyroid disease suggests the feasibility of total thyroidectomy as the operation of choice when surgeons are familiar with the technique and indications. PMID- 2601537 TI - The large vestibular aqueduct syndrome. AB - It has long been known that abnormally large vestibular aqueducts may accompany congenital malformations of the cochlea and semicircular canals. Recently, enlargement of the vestibular aqueducts as the sole radiographically detectable inner ear anomaly has been recognized as a distinct pattern of congenital inner ear malformation. Pathogenesis of the large vestibular aqueduct syndrome probably stems from an early derangement in the embryogenesis of the endolymphatic duct. This anomaly appears to be relatively common in children with sensorineural hearing loss and is probably significantly underdiagnosed. Hearing loss is typically bilateral and progressive, with stepwise rather than fluctuant hearing decrements often triggered by relatively minor head trauma. A review of 17 patients (33 ears) revealed an average hearing level at presentation of 57 dB with a speech discrimination score of 66%. Considerable variability exists in hearing level among affected ears, ranging from normal hearing (4%) to profound deafness (39%). In 12 patients (23 ears) with an average long-term follow-up of 7.3 years, the hearing loss progressed by an average of 25 dB, with a drop of 29% in speech discrimination over the period of observation. An endolymphatic to subarachnoid shunt was performed on seven ears in an effort to stabilize hearing. Four of these ears had a substantial immediate postoperative drop in hearing. For this reason, endolymphatic sac surgery is not recommended for patients with this deformity. PMID- 2601538 TI - Melanomas of the mucous membrane of the head and neck. AB - This is a report comprised of 78 cases of melanoma of the mucous membrane of the head and neck and is part of a larger study of 995 cases of head and neck melanoma. These cases represent a review of patients over a 55-year period from the Pack Medical Foundation. Melanoma of the mucous membrane is a rare condition and the most serious of all head and neck melanomas. Its highest incidence is in the oral cavity, followed by the nasal and pharyngeal cavities. It usually occurs during the fifth decade of life. In its early stages it is asymptomatic and often located in areas difficult to see upon visual examination and technically inaccessible. These facts lead to a delay in diagnosis, which reduces curability to 8%. In spite of these negative factors, there has been a significant improvement in the extension and quality of life for patients with melanoma of the mucous membrane. The biological characteristics of this disease are analyzed and a philosophy of management is offered. PMID- 2601539 TI - Lymphokine-activated killing of autologous and allogeneic short-term cultured head and neck squamous carcinomas. AB - Interleukin-2-(IL-2)-activated lymphocytes have been shown to kill a variety of continuously cultured allogeneic (nonself), natural killer cell-sensitive and resistant cell lines, and some autologous (self) tumor cells. Lymphokine activated killer (LAK) cytotoxicity of autologous head and neck squamous cell carcinoma (HNSCC) cells has not been previously demonstrated, and efforts to demonstrate this have been hampered by the lack of a reliable and reproducible method of obtaining satisfactory tumor targets. In this study, fresh tumor cells were enzymatically dissociated, enriched by adherence to plastic, and used in a 3 hour chromium-51 cytotoxicity assay. Peripheral blood lymphocytes (PBLs) were incubated for 3 days with or without added IL-2. IL-2-activated PBLs showed significant cytotoxicity against autologous and allogeneic targets, while only low levels of tumor lysis occurred with unstimulated PBLs. These findings suggest the possible use of IL-2-activated lymphocytes in the adoptive immunotherapy of HNSCC patients. PMID- 2601540 TI - 1989 Ogura memorial lecture: mediastinal dissection. AB - The mediastinal dissection was introduced in 1962 to manage an otherwise uniformly fatal problem in head and neck oncology: stomal recurrence of laryngeal, squamous cell cancer. The morbidity and mortality rates continued to be high and the survival rates low, but they were an improvement over those of other treatment plans. Since then, refinements of the ablative techniques and major advances in the reconstructive techniques have significantly decreased morbidity and mortality rates. The most recent data indicate a 45% survival rate at 42 months. It is evident that early diagnosis and staging of stomal recurrences will yield successful results. Because the mediastinal dissection operation is now safe, it should be applied more liberally in head and neck oncology situations such as subglottic extension of laryngeal cancer, advanced thyroid cancers, cervical esophageal and tracheal cancers, and all head and neck tumors with low-nodal disease. PMID- 2601541 TI - Multiple synchronous and metachronous cancers of the upper aerodigestive tract: a nine-year study. AB - This retrospective study was based on 9,089 patients and includes 855 cases (9.4%) of multiple primary cancers treated between 1975 and 1983. Three hundred fifty (42.1%) of these multiple cancers were considered synchronous, while 480 (57.9%) were classified as metachronous. Fifty percent of the metachronous cancers occurred within 31 months after the first primary; the mean time between the first primary and the second primary was 45 months. Approximately 22% of second primaries were found more than 5 years after the initial tumor. Five-year survival rates were higher in metachronous cancers (55%) than in synchronous cancers (18%). Survival rates varied according to the treatment. In 49.4% of synchronous tumors the treatment had to be modified because of the presence of two cancers. In these patients, 5-year survival rates were as low as 8%. In synchronous cancers that required no modification of the treatment, the prognosis was better and the survival rate was 28%. The preferential anatomical location of the second synchronous and metachronous cancers is discussed for first primaries situated in the oral cavity (103 cases), the oropharynx (120 cases), the hypopharynx (92 cases), and the larynx (87 cases). Second primaries in the esophagus were mostly synchronous cancers while, in the lung, second cancers were more frequently metachronous tumors. PMID- 2601542 TI - Nasal polyps: epithelium and goblet cell density. AB - The density of goblet cells was determined in 14 anterior and 15 posterior nasal polyps using the whole-mount method. The specimens were then serial cut and the type of epithelium was determined in nine localities in each polyp. The goblet cell density was correlated to the epithelial type. Pseudostratified, cylindrical epithelium was the prevailing type, occurring in 62% of anterior localities and 78% of posterior localities. Transitional types of epithelium were found in 33% of the anterior and 19% of the posterior localities. Stratified squamous epithelium occurred in 5% and 3%, respectively. The goblet cell density was highest in hyperplastic pseudostratified epithelium, whereas it was four times lower in transitional epithelium and even lower in squamous epithelium. Marked differences in the distribution of epithelium and goblet cell density were found between anterior and posterior polyps, illustrating that the epithelium constantly changes under the influence of air current, contact with other polyps, infection, growth, and age of the polyp as well as other unknown factors. PMID- 2601543 TI - Effect of ultrasonic nebulization of Miraclid on the proteolytic activity in tracheobronchial secretions of rats. AB - Experimental studies of acute inflammation of the tracheobronchial lumen of rats suggest that protease inhibitor increases in tracheobronchial secretions in order to control inflammation. Recent studies have shown that the polyvalent protease inhibitor, Miraclid, derived from human urine, is useful for treating DIC and acute pancreatitis. In view of this information, local administration of Miraclid was expected to diminish acute inflammation of the respiratory tract by creating a favorable balance in the protease-antiprotease system. Before the chemotherapeutic use of locally administered Miraclid, the inhibitory activity of Miraclid on various proteases was first estimated in vitro. Administration of Miraclid by means of ultrasonic nebulization was then investigated in rats. The results can be summarized as follows. 1. During ultrasonic nebulization, the inhibitory activity of Miraclid on protease was decreased by means of mechanical stimulation in comparison to the activity before nebulization. 2. Compared to administration of physiological saline into the tracheobronchial lumen, administration of Miraclid by means of ultrasonic nebulization decreased the fibrinolytic activity in tracheobronchial secretions. PMID- 2601544 TI - Recovery of inspiratory abduction of the paralyzed vocal cords after bilateral reinnervation of the cricoarytenoid muscles by one single branch of the phrenic nerve. AB - The aim of this study was to provide the bilateral reinnervation of the posterior cricoarytenoid (PCA) muscles by the superior root of the right phrenic nerve. In six adult cats, the right phrenic root was anastomosed to the distal stump of the transected recurrent laryngeal nerve (RLN) on the same side. The RLN adductor branch was then cut and anastomosed to a nerve graft whose end was carried contralaterally and sutured to the left RLN or to the left PCA muscle. The phrenic fibers regrowing along the RLN abductor branch reinnervated the right PCA muscle and restored the inspiratory abduction of the right vocal cord in all the animals. In five of the six cats, the fibers regenerated through the RLN adductor branch and the graft reached the left PCA muscle and also restored the inspiratory opening of the larynx on the left side. Histological nerve examination revealed a fairly symmetrical distribution of the regenerated phrenic axons to the right and left PCA muscles. PMID- 2601546 TI - An alternative approach for frontal sinus exposure. PMID- 2601545 TI - Modulation of middle ear immune response by gut immunization. AB - Swallowing of upper respiratory pathogens which may at another time be involved in otitis media with effusion (OME) undoubtedly occurs in many patients. In order to explore the possible immunologic consequences to the middle ear (ME) of such gut exposure, guinea pigs were fed antigen either before or after systemic sensitization. A ME immune response was then elicited by ME antigenic challenge. Feeding before systemic sensitization induced systemic tolerance and blunted both the ME immune response and immune-mediated OME. Feeding after systemic sensitization amplified ME immunity and increased immune-mediated OME. Gut immunization, therefore, provides a potent modulation of ME immune response. Depending upon its timing, pathogen swallowing could produce immune hyporesponsiveness, with lowered resistance to infection but reduced immune mediated inflammation. Alternatively, swallowing could result in immune hyperresponsiveness, with increased resistance but also increased inflammation. PMID- 2601547 TI - Effect of excimer laser radiant exposure on uniformity of ablated corneal surface. AB - The argon fluoride (193 nm) excimer laser is being used to change the anterior corneal curvature for correction of refractive errors. Uniformity of the surface following laser ablation may play an important role in the rate of epithelial healing and amount and type of stromal scarring. To test the effect of radiant exposure (fluence) on surface smoothness, we ablated rabbit corneas with the 193 nm argon fluoride excimer laser at nine radiant exposures from 50 to 850 mJ/cm2. A total energy of 100 J/cm2 was used for each ablation at a frequency of 1 Hz. Scanning electron microscopy demonstrated progressive improvement of surface smoothness with increasing radiant exposures. Transmission electron microscopy demonstrated no consistent increase in thickness to the surface condensate (pseudomembrane) with increasing radiant exposure. Improvement in surface quality associated with increasing radiant exposures may result from a more uniform depth of ablation per pulse in the corneal lamellae that absorb laser wavelengths differently. Radiant exposures at levels where the depth of ablation is the same regardless of increasing energy densities achieve a more uniform surface because inhomogeneities in the beam and variation in energy from pulse to pulse do not affect the ablation rate. PMID- 2601548 TI - Possibility of choriocapillary occlusion under experimental subretinal hemorrhage by photocoagulation with lasers of different wavelengths. AB - To clarify the possibility of occluding choroidal neovascularization in subretinal hemorrhage with various laser wavelengths, lesions of experimental subretinal hemorrhage were photocoagulated with argon, dye, and krypton lasers and were examined by light and electron microscopy. Our experimental results revealed that laser photocoagulation with wavelengths longer than 590 nm was effective in occluding the choriocapillaries under a thin subretinal hemorrhage. Complete occlusion of choriocapillaries was accomplished by red dye laser (630 nm) or krypton red laser. The choroidal lesion coagulated by 590 nm dye laser showed more extensive reaction than the other lesions at a posttreatment interval of 7 days. The red dye laser (630 nm) or krypton red laser is recommended for the treatment of neovascular maculopathy under thin subretinal hemorrhage because of less reaction and complete occlusion of the choroidal neovascularization. PMID- 2601549 TI - Characteristics of 308 nm excimer laser activated arterial tissue photoemission under ablative and non-ablative conditions. AB - The present study was designed to assess the characteristics of tissue photoemission obtained from normal and atherosclerotic segments of human postmortem femoral arteries by 308 nm excimer laser irradiation of 60 ns pulsewidth. Three ablative (20, 30, and 40 mJ/pulse) and three non-ablative (2.5, 5, and 10 mJ/pulse) energy fluences were employed. Both the activating laser pulses and the induced photoemission were guided simultaneously over one and the same 1,000 micron core optical fiber that was positioned in direct tissue contact perpendicular to the vascular surface. The spectral lineshape of normal arterial and noncalcified atherosclerotic structures was characterized by a broad continuum, double-peak emission of relevant intensity between wavelengths of 360 and 500 nm, with the most prominent emission in the range of 400-415 (407 nm peak) and 430-445 nm (437 nm peak). Fibrous and lipid atherosclerotic lesions, however, exhibited a significantly reduced intensity at 437 nm compared to normal artery layers (P less than 0.001), expressed as a 407/437 nm ratio of 1.321 +/- 0.075 for fibrous and 1.392 +/- 0.104 for lipid lesions. Normal artery components presented with approximately equal intensity at both emission peaks (407/437 nm ratio: intima, 1.054 +/- 0.033; media, 1.024 +/- 0.019; adventitia, 0.976 +/- 0.021). Comparison of spectral lineshape obtained under various energy fluences within a group of noncalcified tissues disclosed no substantial difference using the 407/437 nm ratio (P greater than 0.05). In contrast, calcified lesions revealed high-intensity multiple-line (397, 442, 461, and 528 nm) emission spectra under ablative energy fluences, whereas a low-intensity broad-continuum, single-peak spectrum resulted from irradiation beyond the ablation threshold. Thus, these findings suggest fluorescence phenomena for broad-continuum spectra, and plasma emission for multiple-line spectra as an underlying photodynamic process. Regardless of the activating energy fluence, spectral analysis of 308 nm activated photoemission provides accurate information about the laser target under standardized in vitro conditions. It is demonstrated that direct contact ablation and simultaneous spectral imaging of the target tissue via the same optical fiber is feasible.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2601550 TI - Alteration of spectral characteristics of human artery wall caused by 476-nm laser irradiation. AB - Fluorescence spectroscopy is a promising new technique for discrimination of normal and atherosclerotic arterial tissues. It has been suggested that this technique be used as a guidance system for laser angiosurgery catheters; however, irradiation by 476-nm light can change the spectroscopic properties of arterial tissue. We present studies that establish intensity levels and exposure times at which alterations in tissue spectral properties are minimal. We also investigate the nature of spectral alterations following exposure of normal human aorta to high intensities of 476-nm laser light. Changes in laser-induced fluorescence (LIF) are characterized by two prominent features: the peak fluorescence intensity decreases permanently, and the fluorescence lineshape changes in a largely reversible way. We relate these changes to alterations in individual tissue chromophores: permanent changes in absolute fluorescence intensity are due to irreversible changes in tissue fluorophores, reversible changes in fluorescence lineshape are due alterations in tissue absorbers. A simple kinetic model is used to describe the decrease in absolute fluorescence intensity. PMID- 2601551 TI - Catastrophic injury secondary to the use of coaxial gas-cooled fibers and artificial sapphire tips for intrauterine surgery: a report of five cases. AB - Five women undergoing endometrial ablation with the Nd-YAG laser developed sudden gas embolism. In each case laser intrauterine contact surgery was carried out utilizing coaxial fibers with (three cases) and without (two cases) artificial sapphire tips but commonly cooled by air or nitrogen. Four of the five women died in a sequence of sudden cardiovascular collapse followed by irreversible cardiac arrest. One woman was critically ill and following prolonged hospitalization survived with neurological deficits. PMID- 2601552 TI - Helium-neon laser-induced respiratory burst of phagocytic cells. AB - The effect of He-Ne laser radiation (lambda = 632.8 nm, I = 6.8 W/m2, irradiation time from 5 to 50 sec) on kinetics of spontaneous and Candida ablicans-stimulated chemiluminescence of mouse spleen cells was studied. It was found that laser radiation caused significant enhancement (180-250%) both of spontaneous chemiluminescence and Candida-induced chemiluminescence. The effective dose interval ranges from 100 to 300 J/m2, with a maximum at 200 J/m2. This finding shows that He-Ne laser irradiation can induce the respiratory burst (generation of reactive oxygen species having bactericidal activity) of phagocytic cells. PMID- 2601553 TI - Lactate dehydrogenase in laser incisions: a comparative analysis of skin wounds made with steel scalpel, electrocautery, superpulse--continuous wave mode carbon dioxide lasers, and contact Nd:YAG laser. AB - A histochemical method for demonstrating lactate dehydrogenase activity was used in addition to standard Van Gieson stain to study early alterations near wounds made in pig skin by steel scalpel, electrocautery, two modes of CO2 laser (the rapid super-pulse mode and the continuous wave mode), and contact Nd:YAG laser. The enzyme-free zone near the wounds made using the thermal knives appeared to be twice as wide as the necrotic zone observed with Van Gieson stain. In polarized light, the enzyme-free area showed two zones of equal width with respect to birefringence of collagen fibers. The zone lacking birefringence correlated well with that observed with Van Gieson stain. The birefringent zone represented functionally damaged tissue with more or less normal structures by light microscopy. The damage to adjacent tissue caused with the thermal knives seems to be considerably larger than has usually been reported. PMID- 2601554 TI - Effect of Nd:YAG laser energy on articular cartilage healing in the dog. AB - The effect of low dose neodymium:yttrium aluminum garnet (Nd:YAG) laser therapy on cartilage healing was studied. Partial- and full-thickness cartilage defects were surgically created in the femoral condyles of 20 adult dogs. The cartilage defects in one limb of each dog were exposed to 30 J of Nd:YAG laser energy. The dogs were euthanatized 1 week (n = 6), 1 month (n = 7), and 6 months (n = 7) after surgery. Plastic-embedded, undecalcified histologic sections of each cartilage defect were examined for evidence of cartilage healing. Special stains were used to determine the type of repair tissue present, and morphometric measurements of repair tissue were made. No effect of Nd:YAG laser therapy on cartilage healing was noted. PMID- 2601555 TI - Abstracts of the American Society for Laser Medicine and Surgery, ninth annual meeting. Arlington, Virginia, April 15-17, 1989. PMID- 2601556 TI - Altered ornithine metabolism in tumor-bearing mice. AB - A flux of ornithine from the host tissues to the tumor was deduced from the concentrations of ornithine in plasma, ascitic liquid, liver and tumor cells during tumor growth. The activities of arginase and ornithine decarboxylase in both liver and tumor cells confirmed this proposed ornithine supply. Moreover, "in vitro" incubations of tumor cells showed that glutamine could be an additional source of ornithine for tumors. Finally, shortly before death, when tumor cell proliferation had ceased, altered hepatic ornithine metabolism was also detected. PMID- 2601557 TI - Platelet serotonin levels and gonadal hormones in rats. AB - The role of gonadal hormones in the control of platelet serotonin levels was studied by evaluating the effect of sexual maturation in rats of both sexes and the time-course of changes following gonadectomy performed either prepubertally or on sexually mature animals. In males, platelet serotonin levels remained fairly stable during sexual maturation as well as during the whole postgonadectomy period monitored (four months). In females, somewhat higher values of platelet serotonin levels in adult than in sexually immature animals were found (9%, p less than 0.001, N = 34). A slight decrease of platelet serotonin (10-18%, p less than 0.05) was observed following ovariectomy of sexually mature females, but it was of transient nature. When females were ovariectomized prepubertally a tendency towards permanently lower platelet serotonin levels was noticed. These results suggest that gonadal hormones have no major role in the control of platelet serotonin levels in rats, although a subtle hormonal modulation of this platelet variable in females may exist. PMID- 2601558 TI - Acid-base, plasma lactate and glucose changes in the rabbit following administration of Gaboon viper (Bitis gabonica) venom. AB - The acid-base and metabolic effects of Bitis gabonica venom administered intravenously to the anaesthetised rabbit were studied. Doubling doses of venom from 0.125 mg/kg to 1.0 mg/kg were used. Venom caused progressive and significant increases in plasma glucose and plasma lactate levels although oxygen consumption only became significantly lower after the fourth dose. Standard base excess (SBE) became significantly more negative after the third dose of venom and the fall in pH became significant at the same point. The results indicate that venom induces a metabolic acidosis in the rabbit and because the acidosis occurs in the absence of any fall in arterial PO2, it cannot be considered a consequence of impaired pulmonary ventilation. The reduction in oxygen uptake is likely to occur at a cellular level with a shift from aerobic to anaerobic metabolism hence the increase in plasma lactate levels. However, the magnitude of the acidosis is unlikely to be the principal cause of death under experimental conditions. PMID- 2601559 TI - Prevention of nonspecific lysis in liposomal and erythrocyte immunoassay systems by small lipid vesicles and erythrocyte ghosts. AB - Large unilamellar liposomes prepared by the reverse-phase evaporation method (REVs) were made immunoreactive by incorporating dinitrophenylaminocaproyl phosphatidylethanolamine (DNP-Cap-PE) or 8-(3-carboxypropyl)-theophylline dipalmitoylphosphatidylethanolamine (Th-DPPE) into the phospholipid bilayer. Specific lysis in the presence of anti-DNP-BSA and goat anti-theophylline serum respectively, was induced by adding guinea pig serum as source for complement to these liposomes. However, specific lysis was found to be compromised by high levels of nonspecific lysis as monitored by the release of the fluorescent aqueous-space marker 6-carboxyfluorescein. Nonspecific lysis could be prevented without affecting specific lysis by pretreatment of complement or incubation of the reaction mixture with small unilamellar liposomes (SUVs). SUVs of various lipid compositions produced the desired effect; however, when the fraction of negative charge in the SUVs was increased to 30 mol%, specific lysis was inhibited as well. In a similar assay system consisting of hemolysin-sensitized sheep red blood cells it was also found that nonspecific lysis could be inhibited by addition of erythrocyte ghosts to the incubation medium, although specific lysis was somewhat depressed. However, SUVs or REVs of a composition similar to sheep erythrocytes were ineffective indicating a more selective nature of complement-mediated immunoreaction with erythrocyte membranes than with synthetic bilayer membranes. PMID- 2601560 TI - Self-administration of morphine contingent on heart rate in the rat. AB - The tendency to associate a given response-reinforcement combination reflects the adaptive significance of the association. Biologically relevant reinforcement can be much more effective in modifying certain responses. For example, treatments that result in various types of illness readily condition aversions to novel flavors, but electric shock is relatively ineffective. While opioid self administration contingent on lever pressing has been extensively studied, the potential for opioids to reinforce visceral responses remains to be determined. An approach to reinforcing changes in heart rate with drug infusions is described. Methods to control for unconditioned drug effects include reversing the direction of change in heart rate required for infusions and addition of a yoked control subject. In several instances, rats exposed to .1 mg/kg infusions of morphine sulfate contingent on tachycardia showed trends for elevated heart rate, with increased locomotor and grooming activity preceding infusions. Increases in heart rate were most pronounced during daytime, normally inactive periods. PMID- 2601561 TI - Comparison of the effects of central and peripheral aluminum administration on regional 2-deoxy-D-glucose incorporation in the rat brain. AB - Intracerebroventricular (ICV) Injection of aluminum tartrate (ALT 205.7 mcg) in the rat induces a progressive encephalopathy characterized by neurobehavioral derangements, by the slowing of the background rhythm of the quantitative electroencephalogram and by learning and memory deficits. The condition, lethal within about 35 days, is associated with a reduced ability of cerebral synaptosomes to incorporate radiolabeled 2-Deoxy-D-glucose (2DG) in vitro. The present study surveyed and compared the in vivo regional cerebral glucose uptake (rCGlu) capacity of rats injected with ALT 7 or 14 days previously either by the ICV or intraperitoneal (120 mg/Kg) routes. ICV injection produces transient rCGlu depression in caudate-putamen, geniculate bodies and periaquaeductal gray, resolving by day 14. Thalamic nuclei exhibit depressed rCGlu by the 7th day undergoing further depression by day 14. The rCGlu of occipitoparietal cortices, normal at day 7, was increased by day 14. In contrast, peripheral aluminum administration produced transient rCGlu depression in olfactory bulbs, frontal and occipitoparietal cortices, nucleus accumbens and cerebellum, and transiently increased rCGlu in the geniculate nuclei. These effects, present by day 7, had resolved by day 14 when rCGlu had increased in the previously normal pontine nuclei and decreased in the previously normal hippocampus. Neither treatment changed rCGlu in the septal nuclei, globus pallidus, amygdala, olfactory cortex, substantia nigra, superior or inferior colliculi or the medullary nuclei. The pattern of anomalies in cerebral 2DG incorporation most probably indexes the deranged glucoregulatory and metabolic demands of these brain areas in the aluminum intoxicated state. PMID- 2601562 TI - The effects of prenatal tertiary butanol administration in CBA/J and C57BL/6J mice. AB - Pregnant mice of the CBA/J and C57BL/6J strains were given either tertiary butanol (10.5 mmoles/kg, p.o.) or an equivalent volume of tap water twice daily from day 6 through day 18 of gestation. Examination on day 18 revealed significantly more resorptions per litter in the t-butanol-treated animals but no interstrain difference. Tertiary butanol did not significantly affect the body weight of the survivors nor produce significant abnormalities in either strain. Subsequent blood concentration profiles in female C57BL/6J mice indicated that the treatment regimen produced blood levels equivalent to teratogenic ethanol treatment. Mice receiving 3 days of t-butanol treatment did not eliminate the drug more rapidly than control animals, indicating that tolerance was not a factor in the treatment regimen. Since t-butanol shares membrane disordering effects with ethanol but is not metabolized by the same pathway, a role for acetaldehyde or the process of ethanol metabolism is suggested in ethanol teratogenicity. PMID- 2601563 TI - Methylxanthine effects on caudate dopamine release as measured by in vivo electrochemistry. AB - The effects of caffeine (1,3,7-trimethylxanthine) and theophylline (1,3 dimethylxanthine) on caudate dopamine release were examined in urethane anesthetized and freely moving rats using in vivo electrochemistry. In anesthetized animals, all doses (150, 250, and 500 mumole/kg, i.p.) produced significant decreases in caudate dopamine (DA) release, which were 14%, 30% and 58%, respectively, at 30 min. The decrease in caudate DA release appeared to be a selective effect with respect to drug and brain region. D-amphetamine (37 mumole/kg, i.p.) increased the caudate signal over a 150 min period. Caffeine, 250 mumole/kg, increased norepinephrine (NE) release in hippocampus by 37% at 30 min and 58% at 150 min. Motor cortical NE release was increased by 8% at 30 min and 44% at 150 min. In freely moving rats, caffeine and theophylline, 75 mumole/kg, increased caudate DA release by 39% and 66%, respectively, at 60 min. Caffeine, 250 and 500 mumole/kg, decreased caudate DA release by 31% and 52%, respectively, at 30 min. Theophylline, 250 mumole/kg, increased release by 25% at 75 min. A 500 mumole/kg dose of theophylline decreased caudate DA release by 44% at 30 min. Measurement of caudate methylxanthine concentrations showed that caudate caffeine levels were significantly higher than those of theophylline. These data are the first to show in an intact animal that methylxanthines affect the regional release of catecholamines (CA) in the central nervous system. This effect is dose dependent. PMID- 2601564 TI - Tissue concentrations of MPTP and MPP+ in relation to catecholamine depletion after the oral or subcutaneous administration of MPTP to mice. AB - One hour after MPTP was given to mice at a dose of 30 mg/kg s.c., its concentration in tissues varied in the order kidney greater than liver greater than lung greater than brain greater than heart. When the same dose of MPTP was given orally, concentrations in most tissues were much lower at 1 hr than after s.c. administration, although the MPTP concentration in liver was only slightly lower. The concentrations of MPP+ (a metabolite of MPTP) at 1 hr were as high or higher than those of MPTP in all tissues except kidney, and MPP+ disappeared from the various tissues with half-lives from 3-20 hrs. The highest concentrations of MPP+, both absolute and relative to MPTP, were in heart. After oral administration of MPTP, no MPP+ was found in brain, and MPP+ concentrations in other tissues were lower than those after s.c. dosing. The depletion of heart norepinephrine was similar after MPTP administration by either route of administration even though MPTP and MPP+ concentrations in heart were lower after oral administration, suggesting that other metabolites of MPTP might also contribute to heart norepinephrine depletion. PMID- 2601565 TI - Sterile sorting of Leu-11a-positive cells (NK cells) using flow cytometry and the antineoplastic effects on brain tumors. AB - Though we recently found some reports on sterile sorting of natural killer cells (NK cells) by flow cytometer (FCM), which manifested cytotoxicity, no reports have concerned antineoplasticity of sterile NK cells on glioma cell lines and cultured surgical materials of brain tumor so far as we know. Monocytes were sampled from the peripheral blood of healthy adults, stained with fluorescein isothiocyanate (FITC)-labeled antihuman monoclonal antibodies, and sorted by an FCM, which had been sterilized with 0.5% Hibitane alcohol solution. Over 95% of the cells obtained were NK cells, and their viability was disclosed to be 97% by the FDA staining. Using thus obtained NK cells, the antineoplastic effects were evaluated in 3 kinds of glioma cell lines and 5 surgical specimens by the microcytotoxicity test. The effects varied widely from 9 to 74% (E/T ratio 40) for glioma cell lines, and from 1 to 66% (E/T ratio 10-40) for surgical specimens. It is expected in the future to apply NK cells clinically using this sterile sorting technique. PMID- 2601566 TI - pH- and time-dependent inhibition of rat kidney neutral endoprotease 24.11 by thiorphan and phosphoramidon. AB - The potencies of thiorphan and phosphoramidon as inhibitors of neutral endopeptidase 24.11 (NEP) are significantly affected by pH. Thiorphan and phosphoramidon are 10- and 150-fold more potent, respectively, when measured at pH 6.5 than at pH 8.5. The kinetic characteristics of these two inhibitors are different. NEP activity is readily inhibited by phosphoramidon upon mixing, while thiorphan becomes a more potent inhibitor only after preincubation with the enzyme. PMID- 2601567 TI - Hyponatremia-induced brain edema in guinea pigs is reduced by treatment with the novel anion transport inhibitor L-644,711. AB - Cerebral edema in various disease states may result from astroglial swelling due to increased NaCl uptake mediated by enhanced Cl-HC03 exchange. We evaluated this mechanism in the pathogenesis of cerebral edema in acute hyponatremia by administering L-644,711, a fluorenyloxyacetate derivative that functions as an anion exchange inhibitor, to guinea pigs with severe reductions in serum Na+ concentration. Acute hyponatremia was induced for 54 hr by daily injections of arginine vasopressin (10 U/day) and 5% dextrose in water (7.5% body wt/day). Experimental animals received L-644,711, 20 mg/kg/day, while controls were given an equal volume of the diluent. This regimen lowered the serum Na from normal levels to 108 +/- 3 and 109 +/- 4 mM in experimental and control animals, respectively. Drug treatment resulted in less cerebral edema characterized by a reduction in brain total tissue water 432 +/- 4 vs 466 +/- 8 ml/100 g dry wt experimental vs control, P less than 0.005. This difference was composed mainly of less expansion of the intracellular water space, 287 +/- 11 vs 323 +/- 9 ml/100 g dry wt experimental vs control, p less than 0.005. The cerebral cortical Na+ +Cl content was reduced from 55.5 +/- 1.3 (control) to 39.5 +/- 1.1 mEq/100 g dry wt (experimental), p less than 0.01. These results indicate that treatment of guinea pigs with L-644,711 decreases brain NaCl content and attenuates cerebral edema during severe acute hyponatremia without normalizing the serum Na+ concentration. PMID- 2601569 TI - The effects of minoxidil on the development of the chick embryo. AB - The effects of minoxidil were studied on chick embryos of 24 and 48 hours of incubation. Minoxidil (3%) was injected into the air sacs of the eggs at doses of 20, 30, 40, and 50 microliters per egg. The controls received 100 microliters of physiological saline. All the embryos, including controls, were examined at day 13. The total number of eggs used in this study was 300. At 24 hours incubation, the percentage of survival ranged from 87 to 21 as the dosages of minoxidil were increased from 20 microliters to 50 microliters per egg (controls = 87%). The survival of the embryos ranged from 79% to 9% after the 48-hour treatment with the similar dosages of minoxidil utilized for the 24-hour group (controls = 83%). A low incidence of gross malformations such as twisted limbs, abnormal beak, short neck and everted viscera were observed; however, the increased incidence was not statistically significant when compared to controls. Body hemorrhage and edema were of high occurrence among the treated embryos. These effects are probably secondary to the known pharmacological effects of minoxidil. The frequency and types of gross malformations did not vary much in the 24 or 48-hour treated groups. PMID- 2601568 TI - Osteotoxicity after chronic dietary administration of 13-cis-retinoic acid, retinyl palmitate or selenium in mice exposed to tumor initiation and promotion. AB - In view of the clinical trials of retinoids as therapeutic agents for premalignant skin lesions, a radiographic study was undertaken to measure skeletal toxicities after chronic dietary administration of retinoids in mice exposed to tumor initiation and promotion. CD-1 mice were initiated with 0.15 moles of 7,12-dimethylbenz[a]anthracene and promoted twice daily with 8 nmoles of 12-0-tetradecanoylphorbol-13-acetate for 23 weeks. Diets were supplemented with 60 IU, 200 IU, or 700 IU of retinyl palmitate (RP) per g diet. After 5 weeks, the 700 IU of RP /g diet was lowered to 350 IU/g diet. Administration of these diets to mice during the 23 weeks of tumor promotion resulted in a 0-fold, 2-fold, or 10-fold increase in bone fractures, respectively. Osteoporotic bone lesions identified on radiographs rose 0-fold, 0-fold, and 10-fold at the respective doses, whereas metaphyseal flares increased 0-fold, 1.4-fold, and 3.6-fold. Bone deformities were augmented 0-fold, 1.8-fold and 2.9-fold at the respective doses. Addition of selenium (2 ppm in the drinking water) did not alter the bone toxicity of RP. 13-cis-retinoic acid (CRA) was less toxic at 700 IU/g diet than was RP at that dose, as evidenced by the death of 12 of 70 mice by the 6th week of dietary RP and no deaths in the 35 mice fed 700 IU CRA/g diet for 23 weeks. CRA at 700 IU/g diet resulted in 3/4 as many osteoporotic bones, 1/3 as many bone fractures, 4/5 as many metaphyseal flares, and a similar number of bone deformities as mice fed 700/350 IU/g diet. At the dose of 200 IU/g food, osteotoxicities were similar in the mice fed diets supplemented with RP and CRA. Thus, the light dose of CRA (700 IU/g diet) was less toxic than the high dose of, RP but at a lower dose (200 IU/g), CRA was as osteotoxic as was RP. Bone fractures in mice exposed to prolonged dietary administration of retinoids was a more sensitive index of retinoid toxicity than was body weight. We have detected osteotoxicity in mice at a total dose of CRA which was about twice the total dose used clinically. PMID- 2601570 TI - Evidence for the autocrine inhibition of glycolysis in human fibroblasts. AB - We investigated the mechanism by which glucose refeeding can reverse the enhancement of glycolysis caused by glucose starvation. Human fibroblasts were deprived of glucose for 18 hr and then refed for 1 hr with either (a) medium from sister glucose-starved cultures (controls), (b) fresh, glucose-containing medium (fresh medium), or (c) medium conditioned for 18 hr by glucose-fed cells (conditioned medium). Despite a lower glucose content, conditioned medium was significantly more effective at inhibiting the accumulation of radio-labeled glucose than fresh medium (74 vs. 49% inhibition). The uptake of 2-deoxyglucose was not affected by either medium, indicating that the site of control of glycolysis was distal to glucose transport and phosphorylation. The active principle was heat labile, dialyzable (Mr less than 12,000) and unrelated to the lactate content of conditioned medium. Medium conditioned by cells exposed to 3-O methylglucose did not inhibit glycolysis in glucose-starved cells even though long-term exposure to this hexose, like glucose, results in the repression of transport. PMID- 2601571 TI - Effects of calcitonin gene-related peptide on the adenylate cyclase system in cultured rat skeletal muscle cells. AB - Adenylate cyclase (AC) activity in skeletal muscle cells isolated from new born rats was increased with time in culture, indicating the presence of heterologous supersensitivity as in the case of denervation in vivo. The effect of addition of calcitonin gene-related peptide (CGRP) to the cultures of skeletal muscle cells on increase in the AC activity was studied. The increases in AC activity stimulated by CGRP, isoproterenol, NaF and forskolin were depressed by exposure to CGRP (1 microM) for 24 hours, depression of CGRP-stimulated AC activity being the greatest. The extent of reduction in increase in AC activity depended on the concentration of CGRP and duration of exposure. The AC activity stimulated by CGRP was also decreased by exposure to dbc-AMP for 24 hours. When muscle cells were exposed to CGRP for 3 days, no significant difference among the AC activity stimulated by NaF, forskolin and CGRP was seen. These results suggest that exposure to CGRP for one day caused mainly homologous desensitization of the CGRP receptor, whereas exposure for 3-4 days caused heterologous desensitization of the AC catalytic unit, perhaps by elevating the c-AMP level in the cells. These results imply that CGRP, which is located in the motor nerve terminal, may play a role as a physiological trophic factor on skeletal muscle. PMID- 2601572 TI - Heterogeneity of chicken growth hormone (cGH). Identification of lipolytic and non-lipolytic variants. AB - The identification and biological activity of chicken growth hormone (cGH) charge variants is described. On the basis of electrophoresis and immunoreactivity chicken pituitary glands contain at least two "charge" variants (Rf = 0.22 and 0.3) which have different net charge but similar molecular weight (26,300 d). Both are immunoreactive but show different bioactivity with adipose explants, band 0.22 being lipolytic whereas band 0.3 appears to be inactive. The abundance of these cGH bands vary with age, both being higher in young birds and lower in adults. These results suggest that cGH variants may have different biological actions. PMID- 2601573 TI - Changes in the synthesis of histone H1(0) and H1 in rat FRTL-5 thyroid cells exposed to thyrotropin. AB - In absence of thyrotropin (TSH), FRTL-5 rat thyroid cells stop proliferating and lose the functional characteristics of thyroid tissue. FRTL-5 cells regain their differentiated state and their proliferation activity upon addition of TSH. In this study we investigated the synthesis of histone H1 variants and H19(0) in FRTL-5 cells exposed to 10(-8) M TSH, two days after TSH withdrawal. TSH induced the synthesis of some H1 variants and H1. This effect was already evident six hours after TSH addition, thus well before proliferation, DNA or thyroglobulin synthesis was induced. These data indicate that the induction of H1(0) and some H1 variants is an early event after TSH stimulation and may thus be related to the functional differentiation of FRTL-5 cells. PMID- 2601574 TI - Morphine self-administration in the rat during adjuvant-induced arthritis. AB - Rats injected with Freund's adjuvant develop a syndrome resembling human rheumatoid arthritis complete with paw swelling, edema and persistent pain. At the onset of pain, arthritic rats and their pain-free littermate controls (vehicle injection) were allowed to self-administer intravenous morphine (5.0 mg/kg/injection) in a 24 hr/day schedule. Self-injected morphine appeared to provide analgesia in arthritic rats as demonstrated by a decreased sensitivity to applied tail pressure. Arthritic rats self-inject significantly less morphine than pain-free animals. Injection of indomethacin, which alleviates the pain and inflammation of the adjuvant-induced disease, reduces, at least initially, morphine self-injection in the arthritic but not pain-free animals. As the adjuvant-induced inflammation and pain dissipated, arthritic rats rapidly began to increase opioid intake. The presence of persistent pain apparently reduces the addictive properties of morphine. PMID- 2601575 TI - Urethane as an inhibitor of the firefly light reaction. AB - A study has been made to test the hypothesis that general anesthetics such as urethane are able to inhibit light from a firefly reaction mixture. Urethane was found to reduce light emission in a dose-dependent manner, the minimal effective concentration being about 20 mM. Dixon plots gave a Ki value in the range of 175 to 215 mM. Lineweaver-Burk plots showed that urethane increases the apparent Km for ATP and reduces Vmax for the reaction. This is taken to mean that urethane acts as both a competitive and non-competitive inhibitor of the firefly light reaction (mixed-type inhibition). PMID- 2601576 TI - Adrenalectomy increases beta-lipotropin secretion over beta-endorphin secretion from anterior pituitary corticotrophs. AB - Previous studies have indicated that acute stress in vivo or ovine corticotropin releasing hormone (oCRH) in vitro, releases both beta-lipotropin (beta-LPH) and beta-endorphin (beta-END) from the anterior lobe, with beta-END predominating over beta-LPH by 2:1. However, repeated stress shifts this ratio to proportionately more beta-LPH released with re-stress or oCRH in vitro. Alternative hypotheses were that the glucocorticoids released during stress altered the processing of proopiomelanocortin (POMC) or that the increased biosynthetic drive resulted in an inability of the processing enzymes to keep pace with biosynthesis. To distinguish between these alternatives, adrenalectomy studies were performed. Following removal of glucocorticoid negative feedback there is greatly increased secretion of beta-END-IR from anterior lobe corticotrophs with a subsequent increase in biosynthetic drive. Under these conditions of increased biosynthetic drive in the absence of steroids, the corticotroph secretes primarily beta-LPH, suggesting that increased biosynthetic drive alters the posttranslational processing rate of POMC. PMID- 2601577 TI - Blood leukocyte and spleen lymphocyte immune responses in chronically physically active and sedentary hamsters. AB - This study was designed to evaluate the effects of chronic physical activity on the immune response of spleen lymphocytes and whole blood leukocytes of hamsters. Animals were kept sedentary or allowed to exercise spontaneously on running wheels for eight weeks. Physically active animals averaged 12 kilometers per day. The immune response of spleen lymphocytes and whole blood leukocytes was evaluated by 3H-thymidine incorporation in response to Concanavalin A or lipopolysaccharide. There was no treatment effect between physically active and sedentary hamsters in the response of spleen lymphocytes. The immune response of whole blood leukocytes to these mitogens was significantly greater (p less than 0.05) in physically active vs. sedentary hamsters. These results demonstrate that chronic physical activity has the capacity to modulate immunoresponses. PMID- 2601578 TI - Reductions of body fat stores and total plasma cholesterol and triglyceride concentrations in several species by bromocriptine treatment. AB - Administrations (injections and in feed) of bromocriptine, a dopamine agonist that inhibits prolactin secretion, reduced body fat stores and plasma total cholesterol and triglyceride concentrations in several rodent species (Syrian hamsters, Djungarian hamsters, Swiss Webster mice and obese Zucker rats). Body fat indices were reduced by at least 50% in the hamsters and mice within 10-15 days of treatment and by 29% in 8 weeks in the rats. Bromocriptine reduced total plasma cholesterol concentration by 17% in Syrian hamsters, 41% in mice and 30% in rats fasted before blood sampling. In nonfasted obese rats, bromocriptine dramatically reduced both cholesterol (from 440 to 130 mg/dl) and triglyceride (from 1570 to 540 mg/dl) levels compared with controls. These findings offer further evidence for a primary role of prolactin in lipid metabolism and indicate that bromocriptine may be useful for treating obesity and lipid-based cardiovascular disorders. PMID- 2601579 TI - "Hormone-like" effect of adenosine and inosine on gluconeogenesis from lactate in isolated hepatocytes. AB - In isolated rat hepatocytes adenosine and inosine showed a dose-dependent increase in the rate of glucose synthesis from lactate with a Ka of 7.5 x 10(-8) and 9 x 10(-8) M, respectively. Absence of this action was recorded with: IMP, xanthosine, adenine, hypoxanthine, and uric acid. A reciprocal inhibition of individual gluconeogenic stimulation was found in cells incubated with glucagon or epinephrine and adenosine, but not with inosine. 5'-(N-ethyl) carboxamido adenosine was more potent than adenosine, whereas N6-(L-2-phenylisopropyl) adenosine antagonized the stimulation of gluconeogenesis by adenosine. Neither of the analogs used modified the stimulatory role of inosine on the studied pathway. Adenosine and inosine may be involved in the short term regulation of gluconeogenesis. PMID- 2601580 TI - Modulation of the lethal effects of cocaine by cholinomimetics. AB - In view of the toxicity of cocaine and recent reports on the antimuscarinic properties of cocaine, the present study evaluated the effects of manipulations in cholinergic neurotransmission on the lethal effects of cocaine. Physostigmine pretreatment significantly altered the lethality of cocaine, increasing the LD 50 from 82.5 mg/kg to 96.9 mg/kg in male F344 rats. Atropine alone did not alter the lethal effects of cocaine at doses that are effective in preventing parasympathetic effects and lethality of oxotremorine. The prophylactic effect of physostigmine was not prevented by atropine. Neostigmine did not significantly affect the cocaine lethality dose-effect function. Both oxotremorine and (-) nicotine were also devoid of protective actions. At higher doses, all of the cholinomimetics potentiated the lethal effects of cocaine. These results suggest that whereas cocaine lethality may be enhanced by stimulation of muscarinic receptors, low doses of physostigmine protect against lethality through actions at noncholinergic sites. PMID- 2601581 TI - Neuroendocrine and behavioral effects of dietary tryptophan restriction in healthy subjects. AB - The neuroendocrine and behavioral effects of gradual dietary tryptophan (TRP) depletion, utilizing two magnitudes of a 10-day TRP-restriction diet (700 mg/day and 200 mg/day), were studied in 22 healthy subjects. The prolactin response to a 7 gm L-TRP infusion was measured prior to and on day 10 of the diet. Both diets significantly reduced fasting total plasma TRP by 15 to 20%, but only the 200 mg/day TRP diet led to an enhancement of the prolactin response to intravenous L TRP. Female subjects demonstrated a more robust increase in plasma prolactin following L-TRP infusion pre-diet and exhibited a larger decrease in plasma TRP following dietary TRP restriction compared to males. There were no significant behavioral effects of either diet. Gradual dietary TRP depletion leads to an enhancement of the prolactin response to L-TRP infusion, suggestive of postsynaptic serotonin receptor supersensitivity. PMID- 2601582 TI - Possible dopaminergic system involvement in LH and PRL responses to naltrexone treatment. AB - Naltrexone (Nalt) causes a rapid increase in luteinizing hormone (LH) level. This short term increase of LH concentration declines to baseline levels in less than 1 hour. Addition of pimozide (0.1 mg) caused a blunted response to Nalt challenge, with significantly reduced LH peak values compared with Nalt treatment alone. Pimozide alone caused a delayed decrease compared with baseline LH values. By following plasma prolactin (PRL) levels it was shown that pimozide administration increased PRL levels rapidly for more than 2 hours. Addition of Nalt to pimozide-treated rats significantly decreased plasma PRL values compared with pimozide alone. Nalt injected by itself attenuated PRL baseline levels. Thus, the mechanism by which pimozide caused PRL elevated level is via the dopaminergic as well as the opioid system. It is suggested that the opioid system controls plasma PRL and LH levels through other hypothalamic neurotransmitters in addition to dopamine. PMID- 2601583 TI - Testicular proteins, nucleic acids and their synthesis following gamma irradiation. AB - The effects of two doses (250 and 1000 rads) of local gamma irradiation on testes of adult rats are reported after 1, 2, 4 and 16 weeks. There was a significant increase in DNA content per gm testes at 1 week; a gradual decrease at 2 and 4 week intervals was followed by a trend towards recovery at 16 weeks post irradiation. The rate of synthesis of both DNA and RNA as studied by the incorporation of (3H)-thymidine and (3H)-uridine, showed similar results. Total protein content per gm testis declined with both doses and at all post irradiation intervals. Histological observation showed loss of spermatogenic cells suggestive of DNA loss. PMID- 2601584 TI - The effect of debrisoquin on MAO A and MAO B activities. AB - To examine the mode of action of debrisoquin (DEB), we studied the effect of this drug in vitro on MAO A and MAO B enzyme activities. DEB was shown to be a competitive inhibitor of highly purified human MAO A and MAO B enzyme activities. DEB inhibited placental MAO A with a Ki value of 0.5 microM and liver MAO B with a Ki value of 8.8 microM, 18-fold greater effect on the A form. Kynuramine was used as substrate for both enzymes. Additional studies using a dilution technique showed that DEB was a reversible inhibitor of both forms of the enzyme. The results of this study show that DEB is a potent competitive and reversible inhibitor of both MAO A and MAO B enzymes. PMID- 2601585 TI - Superoxide dismutase and alpha-tocopherol suppress the paraquat-induced elevation of N1-acetylspermidine and putrescine in primary culture of adult rat hepatocytes. AB - A transient increase in N1-acetylpolyamines and putrescine (PUT) was observed in hepatocytes at the early stage of primary culture of rat hepatocytes. After pre culture for 36 hr when the polyamine content returned to constant levels, we tested the effects of superoxide dismutase (SOD) and alpha-tocopherol on the paraquat-induced increase in N1-acetylspermidine (N1-acetyl-SPD) and PUT in the culture. Paraquat increased (N1-acetyl-SPD in a dose-dependent manner. It also increased PUT at doses between 0.1 and 1.3 mM. Both SOD and alpha-tocopherol suppressed the increase in N1-acetyl-SPD and PUT induced by paraquat. These results suggested that superoxide anion is one of the factors which increase N1 acetyl-SPD and PUT in hepatocytes. Lipopolysaccharide (LPS) little affected the polyamine concentration in the cultured hepatocytes, though it increases polyamine in mouse liver when given in vivo. These findings suggested that the formation of superoxide anion after administration of LPS in vivo is mediated by Kupffer cells. PMID- 2601586 TI - Lactobionic acid as an iron chelator: a rationale for its effectiveness as an organ preservant. AB - Lactobionic acid, a major constituent of a solution used to preserve organs prior to transplantation, can chelate ferric iron. This is evident by its ability to solubilize iron as well as changes that occur in the UV-VIS spectra of iron in its presence. Relative to iron (III) chelated to EDTA, the lactobionic acid-iron (III) complex is less able to participate in the Fenton reaction as measured by formaldehyde generation from DMSO and bleaching of p-N,N-dimethylnitrosoaniline. Similar effects are seen with citrate and ATP, two substances which also appear to be able to ameliorate ischemia/reperfusion injury. These findings present a rationale for the effectiveness of lactobionic acid as an organ preservant. PMID- 2601587 TI - [Hepatic scintigraphy using 123I-rose bengal]. AB - The paper is devoted to the experience in diagnostic investigations using rose bengal, labeled with half-life 123I (123I-RB). The drug was synthesized in the B. P. Konstantinov Leningrad Institute of Nuclear Physics, USSR Academy of Sciences. Analysis of the results of investigations of 201 patients with diseases of the liver and biliary tracts revealed the advantages of 123I-RB over standard RPs of similar diagnostic purpose. Owing to low radiation exposure one could use higher activity (up to 120 MBq and more) of the drug. It made it possible to combine a study of the functional parameters of the hepatobiliary system and obtaining scintigraphic data on the structure of the liver and biliary tracts. 123I-RB is the best radiodiagnostic agent for a study of function and topography of the liver in patients with an increased blood level of bilirubin. PMID- 2601588 TI - [The effect of the measurement matrix on the quality of statical scintigraphic research]. PMID- 2601589 TI - [Radioanatomy of cerebral perfusion in single-photon emission-computed tomography using 99mTc-labelled amines]. AB - A study was made of the cerebral hemodynamics by assessing the distribution in single-photon emission computerized tomography with 99mTc-hexamethyl propyleneminoxyne in health using a Testascan in 9 standard slices. The whole set of tomographic slices was conventionally divided into 3 levels. For better orientation in gamma-tomographic images, pictures were presented where in addition to scintigrams a morphological scheme of the cerebral parts with the marked parts perfused by cerebral arteries, was given. PMID- 2601590 TI - [Radiation and combined treatment of anaplastic neuroepithelial neoplasms]. AB - The data on 645 patients with anaplastic neuroepithelial tumors subjected to radiotherapy, irradiation with radiosensitizers (metronidazole) and chemoradiotherapy are presented. Total-differential brain irradiation was applied: 10-40 Gy on the whole brain and 10-20 Gy on the tumor bed. Fractionation depended on tumor radiosensitivity. The median survival time for anaplastic astrocytoma was 50 +/- 5.6 mos., oligodendroglioblastoma - 42 +/- 7.4 mos., ependymoblastoma - 61 +/- 8.2 mos. and glioblastoma - 22 +/- 1.5 mos. High-dose dynamic fractionation proved to be most effective in cases of glioblastoma. The outcome of glioblastoma was modified neither by radiosensitizers nor by cytotoxic agents. PMID- 2601591 TI - [Radiation therapy of stage III laryngeal cancer]. AB - As a result of a marked effect of the 1st stage of radiation therapy of 44 patients with stage III (T3N0M0) laryngeal cancer it was followed by therapy after a radical program up to a summary focal dose of 65-70 Gy. Continued tumor growth and recurrences were diagnosed in 19 patients, of them radical operation was performed on 12, 25 patients (57%) have been followed-up for 3 years, without signs of either recurrence or metastases with the preserved larynx. The above results suggest the effectiveness of radiation therapy in locally advanced laryngeal cancer. PMID- 2601592 TI - [The immunomodulating action of combined therapy together with local UHF hyperthermia in osteogenic sarcoma in children]. AB - The paper is concerned with immunological evaluation of different stages of combined therapy with local UHF hyperthermia in children with osteogenic sarcoma. Combined therapy (polychemo- and radiotherapy) was shown to cause a decrease in the number of immunocompetent cells, to enhance imbalance of immunoregulatory T lymphocytes, to weaken T-lymphocyte function on PHA; immunosuppressive action of combined therapy did not depend on a tumor site. The incorporation of UHF hyperthermia in the therapeutic scheme weakened the manifestations of secondary immunodeficiency, got back to normal the structure of T-lymphocyte population. A favorable immunomodulating effect of hyperthermia was more frequently observed in patients with crural bone tumors. The effect of hyperthermia was revealed after direct influence of thermotherapy but it was absent in continuation of combined treatment. PMID- 2601593 TI - [Dynamic fractionation of the radiation dosage combined with the local use of metronidazole in bladder cancer]. AB - The paper is devoted to the description of the combined methods of radiotherapy of urinary bladder cancer and the local use of metronidazole. At the 1st stage of therapy a dose of 140 cGy twice a day with 5-6 h interruption was delivered up to a summary dose of 43 Gy on conversion to small fractionation by the TDF factor. Then two fractions at a single dose of 6 Gy once a week were given. Altogether 36 patients were treated by this method. The control group of patients was given radiation therapy in a split course in the regimen of routine fractionation. Short-term therapeutic results were analyzed for both groups. The total positive effect was higher in the study group (81.25% versus 66.7%). A conclusion is that this method holds promise. PMID- 2601594 TI - [The lactate dehydrogenase isoenzyme spectrum and total activity as a prognostic sign in the radiation treatment of esophageal cancer]. PMID- 2601596 TI - [Inducing effect of periodontopathic bacteria on activation of macrophage functions and production of interleukin-1 by mouse peritoneal macrophages]. AB - Periodontal disease is thought to be initiated by a bacterial infection and subsequently developed by immunopathological mechanisms thorough host-parasite interactions. The macrophage and lymphocyte are the major functional cell types in the lesion of the disease and participate in tissue destruction and alteration of the periodontal connective tissue as well as in host defense mechanisms. However, the detailed implications of macrophages in development of the disease is still unclear. The aim of this study was to gain more understanding of the functional role of macrophages in periodontal disease. In this study, we examined the inducing effects of sonicated extracts from some gram-negative and gram positive bacteria associated with the pathogenesis of periodontal disease, including Bacteroides gingivalis, Fusobacterium nucleatum, Haemophilus actinomycetemcomitans, and Actinomyces viscosus, on activation of macrophage functions and IL-1 production by the macrophages from the mouse peritoneum. At a dose as low as 1 microgram/ml (dry weight) sonicated extracts from B. gingivalis induced an increase in acid phosphatase activity and in glucose consumption of mouse peritoneal macrophages in vitro. A significant increase in the acid phosphatase and in glucose consumption was observed in the cultures at 24 h and 48 h, respectively, after the addition of the sonicate. Sonicated extracts from A. viscosus, a gram-positive bacterium, as well as B. gingivalis, F. nucleatum, and H. actinomycetemcomitans, gram-negative ones, were able to induce the increase in acid phosphatase activity and in glucose consumption of the macrophages. These periodontopathic bacteria were found to strongly induce IL-1 production by the macrophages as early as 24 h after addition of the sonicates. A significant increase in the IL-1 production was observed at a dose of 1 microgram/ml of the sonicates. The inducing ability was equivalent to 1 microgram/ml Escherichia coli lipopolysaccharide. The highest production of IL-1 was observed in the macrophages treated with H. actinomycetemcomitans among these sonicates. Sonicated extracts from both gram-negative and gram-positive bacteria were able to induce the IL-1 production by macrophages from C3H/HeJ mice, which are LPS low-responders. These results suggest that periodontopathic bacteria have potent ability to induce macrophage activation and IL-1 production and that the activated macrophages may play an important role in development of periodontal disease.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2601595 TI - [Late radiation injuries of the urinary tract]. AB - A total of 400 patients with radiation injuries of the organs of the small pelvis were examined. Urinary dysfunction was found in 115 of them. Radionuclide renography with 131I-hippurane, excretory urography and ultrasound scanning were employed for their investigation. The principal cause of urinary dysfunction was the development of intrapelvic radiation fibrosis with ureteral compression and direct radiation injury of the ureter. PMID- 2601597 TI - [Genetic study of ovary development in Drosophila lutescens]. AB - Experiments were carried out in order to clarify the genetic mechanism governing the development of ovaries of Drosophila lutescens female flies. Female flies of two strains obtained from northern (Niigata) and southern (Tokunoshima) parts of Japan, F1, F2, and backcrossed hybrids were examined. Female flies, one week after emergence at 14 degrees C, during which time they were kept under a 10 h 30 min light/13 h 30 min dark regimen, were dissected, and they were divided into three classes: those with mature, retarded, and undeveloped ovaries. The ratio of undeveloped ovary in the northern strain was much higher than that of the southern. From the results of all dissections, it is assumed that genes on chromosomes of the northern strain operate to stop ovarian development and that cytoplasmic factors of the southern strain act to suppress those genes. It may be, therefore, suggested that the development of the ovary of this species before hibernation is controlled genetically. PMID- 2601598 TI - [A case of bilateral impaction of the lower second molars]. AB - A case of bilateral impaction of the lower second molars is presented. A 15-year old boy with an ill feeling at the right lower first molar was referred to us. X ray examination revealed bilateral impaction of the lower second molars and the presence of bilateral teeth that seemed to be the unerupted third molars distal to the impacted second molars. Furthermore, a radiolucency approximately 3 X 3 mm in size was detected in the mesioapical region of the right lower first molar. These impactions were managed under local anesthesia by extraction of the right lower first molar and fenestration of the right lower second molar. After approximately 4.5 months, the right lower third molar was extracted. It was further followed approximately 1 month later by extraction of the left lower third molar and ipsilateral fenestration of the lower second molar. As a result, the right lower second molar erupted but it was considerably inclined in a mesial direction. The left lower second molar erupted normally almost up to the occlusal plane. In the absence of systemic abnormality, facial trauma, and maldevelopment of the jaw, impaction seemed to have been closely associated with some unknown local factor. PMID- 2601600 TI - [Clinical prospective study of surgical treatment of pterygium]. AB - Pterygium is a kind of degenerative lesion of the ocular conjunctiva and is thought to be hyperaemia of fibrovascular tissue onto the cornea caused by various factors. The most frequently used treatment for pterygium at present is surgery. Various surgical procedures and postoperative treatments for pterygium have been reported, however, the postoperative recurrence rates are somewhat high. Therefore, until now we have had no satisfactory clinical management of pterygium. The results of our method for surgical treatment of pterygium are given and compared with those described in many other reports. From this comparison, our clinical surgical treatment of pterygium, which is the so-called "bare sclera" technique, is evaluated to give the best management without serious complications and recurrences. PMID- 2601599 TI - [The effect of fluoride-containing tooth paste on dental plaque and on fluoride level in the mouth]. AB - Various kinds of fluoride have been used for a long time and there are many reports concerning fluorides and their effects. Recently, the caries-inhibiting action of fluoride-containing tooth paste has been given much attention. In this study, I tried to clarify the residual time and amount of fluoride derived from the fluoride-containing tooth paste in the mouth, as well as to assess possible variation in bacterial composition in the dental plaque bacteriologically and biochemically. In the study on the fluoride clearance from the mouth, both 1.0 g and 0.5 g of paste showed the same reduction rates; and about an 80% reduction was recognized between the value at 3 minutes and that at 30 minutes, and about a 40% reduction from the 30-minute to the 60-minute interval. Next, a study on the variation in plaque bacteria was carried out. The total number of the CFU on each plate was not different between samples obtained before and after the use of the tooth paste; moreover, no difference was noted between aerobic and anaerobic culture. However, when plaque before and after brushing with fluoride-containing tooth paste were cultured in 10% sucrose solution, the differences of acid production such as lactic acid, acetic acid, and formic acid were demonstrated. Namely, these acid productions were inhibited after the use of fluoride, especially lactic acid was strongly inhibited. On the other hand, when Str. mutans from the plaque obtained after the use of fluoride-containing tooth paste was cultured in fluoride-free BHI broth, the inhibition of acid from carbohydrates was not shown clearly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601601 TI - [Electron microscopic observation of the soft tissue in the gubernacular canal. 3. Changes in the components with aging]. AB - In the present study, we observed the epithelial remnants in the gubernacular canal of a 3-month-old crab-eating monkey by transmission electron microscopy, and compared our findings with those in a 1-year-old one. The following results were obtained: 1. The basal lamina of the epithelial remnants of the 3-month-old monkey was more clearly seen than that of the older animal, and it had a brush like appearance probably due to relatively high forming activity. 2. No marked difference was observed among the cellular components between the two ages. The tonofilaments which were fibrous in ordinary epithelial cells already showed some aggregation and granular appearance in the 3-month material. 3. In most parts of the 3-month-old material, only a small number of atrophied cells were observed; however in the epithelial remnants located near the gingival epithelium, we observed cells containing swollen mitochondria which probably occurred due to the degeneration of the cells. 4. The density of collagen fibers around the dental germ was relatively low, whereas in the area close to the gingiva, the density of fibers was very high. 5. In the present study, no components exactly derived from the remnants of epithelial cells were observed within the extracellular spaces of the connective tissue. PMID- 2601602 TI - [Effect of inorganic anions on the activity of dental pulp lactate dehydrogenase]. AB - Pig dental pulp lactate dehydrogenase (EC. 1.1.1.27; LDH) isozymes were separated by DEAE Sephadex A-50 column chromatography, and LDH-1 isozyme was purified by blue dextran affinity chromatography. The specific activity of pig dental pulp LDH-1 was 193.2 units/mg protein, and the purified enzyme showed a single protein band on disk electrophoresis. In this paper, we studied the effect of inorganic ions on the activity of pig dental pulp LDH-1 isozyme, and compared it with that of affected by anions. Dental pulp and heart muscle LDH-1 isozymes were inhibited at a low pyruvate concentration; otherwise, at a high pyruvate concentration, each enzyme activity was enhanced by the anions. But the effect of SO2(2-) was different from that of the other anions: SO2(2-) did not activate the enzyme at a high pyruvate concentration. In the dental pulp, the Km values for pyruvate were 1 order of magnitude smaller by SO2(2-), and 1 order higher by other anions than the control value. In the heart muscle, the Km values were not changed by anions, except by SO2(2-). PMID- 2601603 TI - Study on vibrations of the mandible. AB - In order to elucidate the phenomenon of vibrations of the mandible, a simplified plaster model was prepared and the fundamental vibrations were investigated. Studies using either dried human skulls or in situ mandible yielded similar results. The results obtained were as follows: 1. The vibrations generated by tapping a simplified mandible model were similar to those of the transverse type of a bar and tuning fork. 2. Both vibration models belonged to the transverse type bar vibrations. 3. Similar results were obtained by tapping the teeth of the mandible in situ. 4. The presence of fractures and cysts in the mandible might induce changes in vibrations. PMID- 2601604 TI - [Effects of various factors involved in bone metabolism on 45Ca2+ incorporation and alkaline phosphatase activity of ROS 17/2.8 cells]. AB - The effects of interleukin 1, transforming growth factor-beta (coupling factors), prostaglandin E1, and prostaglandin E2 on incorporation of 45Ca2+ and on alkaline phosphatase activity were studied using cultured ROS 17/2.8 cells, one of cell lines derived from rat osteosarcoma. We found that all these factors stimulate both the incorporation of 45Ca2+ and alkaline phosphatase activity of these cells. On the other hand, one of the bone resorption hormones, parathyroid hormone (PTH), suppressed the proliferation of cells and decreased the alkaline phosphatase activity at considerably low concentrations (1 X 10(-12)-1 X 10(-11) M). However, the hormone stimulated the incorporation of 45Ca2+ by these cells in a dose-dependent manner; the maximum stimulation on day 3 was observed at 1 X 10( 7) M and it was approximately 3 times the control value. The data suggest therefore, that the osteoblasts incorporated calcium ions and transported them while bone resorption was occurring. Thus the ROS 17/2.8 cell line appears to be an advantageous experimental system for the study of calcium metabolism of osteoblasts in vitro. PMID- 2601605 TI - [Mechanical study on the stability of multiform mini-plates. I. Double-T-type plate (90, regular, 6-holes) in mandibular body fracture]. AB - In this present paper, we reported the stability of osteosynthesis using a special type of mini-plate for mandibular fractures as evaluated from a mechanical study with static loading. The materials used in this study were fifteen bars made of acrylic resin, each divided at the center of its length into two parts to simulate a condition of mandibular body fracture. Following the fixation of these materials with mini-plates firmly attached between their cut ends, the bars were secured in a vice at one end and a static load was applied from the vertical direction at the other end. The amount of displacement of the loaded end was investigated with a displacement-measuring device, and the strains on mini-plates and test bars were measured with strain gauges. A comparative study was conducted on three kinds of mini-plates: 1) Group S, fixed with one Champy mini-plate, 2) Group W, fixed with two Champy mini plates, 3) Group T, fixed with one double-T-type mini-plate. The following results were obtained: 1) The amount of displacement was largest in the vertical direction and smallest in the horizontal direction in the three groups. Especially in group T, it was smaller the longitudinal and horizontal axes than in the other two groups. 2) Longitudinal strain of the plate was smallest in group W. However, the strain on the test bar was smallest group S. Especially , in group T, the largest compressive strain was observed at the lower portion of the synthesized ends.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601606 TI - [A complex resuscitation unit for newborn infants]. PMID- 2601607 TI - [Optimal system of operating the MPU-D-02 machine for washing and disinfection of nursing care equipment]. AB - The authors review different designs of the nozzles for washing assemblies and the possibilities of their use in a washing machine during the washing of bedpans, child pots and urinals. Define optimal variants of the nozzles and their distribution relative to a bedpan and a urinal. Delineate the effect of tap water pressure and temperature on the quality of contamination wash-out from medical appliances as well as tap water consumption required for different designs of the nozzles at varying water pressures and temperatures. Provide the technical characteristics and describe the mode of operation of the machine for washing and disinfection of nursing appliances. PMID- 2601608 TI - [Preparation of water at kidney centers using separating counterosmosis equipment]. AB - A water treatment AKBA-I unit intended for the renal centers was tried. The unit includes a clarifier, an adsorber, a softener, a reflux osmotic separator and electronic systems for the control of hydrodynamic processes. The trials demonstrated the unit to be highly effective as regards the removal from water of salts of hardness, of iron, potassium, oxidizable substances and active chlorine. The pH value of the filtrate (7.1-7.4) appeared to meet the requirements made during the preparation of a dialyzing solution. The concentration of sodium ions in the filtrate was 0.75 mg.eq/l, which did not influence the concentration of sodium ions in the dailyzing solution during its preparation from dry concentrate. During operation of the unit, the selectivity of the APO membrane in the operating mode was defined. It amounted to 85%. PMID- 2601609 TI - [Study of the mode of operation of the equipment for membrane extraction of substances from the blood in emulsions]. AB - The authors suggest an apparatus make-up for cholesterol extraction in multiple emulsion from blood. It is intended for homeostasis correction according to the hemoperfusion scheme with the use of this apparatus instead of the hemoperfusion one. The influence of the velocity of the blood flow, the rate of stirring and emulsion volume on the modes of operation of the apparatus was investigated. The most efficient mode of operation was chosen, according to which the entry of the extracting agent into the body was completely excluded whereas emulsion saturation with cholesterol was reached after 1.5 h. A series of animal experiments were carried out using the same apparatus but 10 times smaller, with the emulsion containing ethanol and diethyl ether in the internal phase. The mean degree of cholesterol extraction amounted to 22.4%, while the main biochemical components of blood remained unchanged. PMID- 2601610 TI - [Prospects of the development and production of medical equipment]. PMID- 2601611 TI - [Prospects of the use of new technology for producing precision instruments from glass]. AB - The purpose of the work is the development and introduction into industry of the technology and equipment for manufacturing precision tubes from glass and other elements for medical instrumentation and equipment. The results of theoretical and experimental works are provided. Possible areas of the use of the technology and equipment are considered. PMID- 2601613 TI - [Problems of rational evaluation of work places based on their accreditation by the "Medical Technology" association]. PMID- 2601612 TI - [New methodologic approaches to solving the problem of determining the requirements for medical technology]. AB - The authors analyze the main causes of the low standards of technical equipment of health institutions; substantiate the necessity of developing progressive standards of fitting out the treatment and prophylactic institutions with medical instrumentation and equipment; elucidate the principles of methodological approaches to the solution of the given problem; disclose the term "functional module" as the totality of the equipment with medical instrumentation of ward departments (reception rooms) of different profiles and subdivisions of the treatment and diagnostic services maintaining their work; describe the main stages of the designing of progressive equipment standards. PMID- 2601614 TI - [The disinfection apparatus DA-4]. AB - The disinfectant units dA-2 and dA-3 manufactured today on an industrial scale are not enough because of ultimate load of the chassis of the motor car. A new one-compartmental movable disinfectant dA-4 unit mounted on the chassis of the motor car gA3-53-12 with high technical performance is characterized by the improved layout of the equipment and can be run in the foci of infection at any time of the year. The dA-4 unit has been approved for manufacture in series. PMID- 2601615 TI - [The orthopedic table OrM-2]. PMID- 2601617 TI - [Equipment for handling ophthalmologic instruments]. PMID- 2601616 TI - [The obstetrical bed KA-2]. AB - An obstetric bed is intended for disposition of parturients during labor as well as for performing obstetric non-cavitary operations and manipulations. The new bed is equipped with a small table for a hand to do intravenous injections. It is also fitted out with a detachable pan representing a vessel stamped of stainless steel, designated for liquid collection and with a detachable step for the sake of convenience of parturients' disposition on the bed, which makes it possible to tilt the bed into Trendelenburg's position. The bed is convenient in handling, modern in appearance, enabling one to carry out wet sanitary treatment. PMID- 2601618 TI - [Possibilities of sterilization of medical equipment using ultrasonics combined with disinfectants and sterilizing agents]. AB - An ultrasound Y3Y-0.25-0 unit was used to reach the sterilizing effect during the treatment of metal surgical appliances packed in a row by means of ultrasound combined with 6% hydrogen peroxide (40 degrees C) for 60 minutes and with 1% (according to peracetic acid) desoxone-1 (18 degrees C) for 45 minutes. This made it possible to attain a 3-fold reduction of the time required for sterilization during treatment of the appliances by combination of ultrasound and 6% hydrogen peroxide as compared to sterilization with the aid of the solution alone under the same conditions. PMID- 2601619 TI - Fulminant hyperkalaemia and multiple complications following ibuprofen overdose. AB - A previously healthy 17-year-old man was admitted in coma following major overdosage with ibuprofen and minor overdosage of doxepin (plasma concentrations 809 and 0.49 mg/L, respectively). Initially, potassium chloride (20 mmol 3 hourly) was infused because of mild hypokalaemia (K+ 2.8 mmol/L). 14 hours after admission the patient developed a hypermetabolic state with pyrexia, metabolic acidosis and progressive respiratory failure despite ventilation at 16 L/min, and a malignant broad complex tachycardia was associated with acute hyperkalaemia (K+ 8.3 mmol/L). The arrhythmia resolved with correction of the hyperkalaemia. Chest x-rays showed diffuse opacification throughout both lung fields and subsequently there was transient impairment of renal function, with evidence of mild rhabdomyolysis. Ventilatory support was required for 60 hours and a chest x-ray at 6 days showed extensive bilateral nodular shadowing, which was still present at follow-up 4 weeks later. PMID- 2601620 TI - Antibodies, antigens and molecular mimicry. PMID- 2601621 TI - Immunoelectron microscopy of idiotype-anti-idiotype complexes. PMID- 2601622 TI - Idiotopes carried by antiallergen antibodies. PMID- 2601623 TI - Structure-function analysis of protein active sites with anti-idiotypic antibody. AB - Antigen and internal image-bearing anti-idiotypic antibody, owing to potential differences in size and chemical nature, need not necessarily demonstrate identical binding specificities. Such differences, termed "dissociability," may be exploited in structure-function analysis of receptor-ligand interaction to identify functionally important amino acid residues, define receptor class, or distinguish receptor conformation. In this sense, ligand and the anti-idiotypes they elicit constitute alternative and complementary probes of protein active sites. PMID- 2601624 TI - Anti-idiotypic antibodies as probes of prolactin receptor. PMID- 2601625 TI - Preparation and use of anti-idiotypic antibodies armed with holotoxins or hemitoxins in treatment of B-cell neoplasms. PMID- 2601626 TI - Use of anti-idiotypic antibody-drug conjugates to treat experimental murine B cell tumors. PMID- 2601627 TI - Anti-idiotypic antibodies in the study and treatment of experimental autoimmune myasthenia gravis. PMID- 2601628 TI - Inhibition of autoimmune reactivity against acetylcholine receptor with idiotype specific immunotoxins. PMID- 2601629 TI - Production of antibodies that mimic enzyme catalytic activity. PMID- 2601630 TI - Design of catalytic antibodies. PMID- 2601631 TI - Computer prediction of B-cell determinants from protein amino acid sequences based on incidence of beta turns. PMID- 2601632 TI - Stress related to neonatal intensive care nursing. PMID- 2601633 TI - HIV blood testing. PMID- 2601634 TI - Midwifery in Canada: Ontario's "alegal" midwives. PMID- 2601635 TI - Quebec--where midwifery is illegal. PMID- 2601636 TI - Deafness in babies. PMID- 2601637 TI - A question of communication. PMID- 2601638 TI - Personal experiences--or ego trips? PMID- 2601639 TI - "allowed to do the work I trained for". PMID- 2601640 TI - Careers convention. PMID- 2601641 TI - Stimulus-activated changes in brain tissue temperature in the anesthetized rat. AB - A new thin-film, multisensor probe was used to determine tissue oxygen tension, tissue temperature, and electrical activity at two depths below the brain surface in chloral hydrate- or nitrous oxide/halothane-anesthetized rats. Brain tissue temperature at both depths was found to be lower than core temperature by 1-2 degrees C. Electrical activation, spreading depression, and pentylenetetrazol seizures all resulted in transient increases of brain tissue temperature of a few tenths degree centigrade. Vasodilation, induced by hypercapnia or hypoxia, caused a warming of brain tissue. Near-maximum oxygen metabolism, reached upon reoxygenation after severe hypoxia, was accompanied by tissue temperature rises of greater than 1 degree C. It was concluded that brain tissue temperature in the anesthetized rat is lower than core temperature due to extensive radiative and conductive heat loss to the environment through the head. Transient increases in tissue temperature during activation are caused by vasodilation and increased metabolism. PMID- 2601643 TI - Induction of heat shock protein 70 mRNA in adult hamster facial nuclear groups following axotomy of the facial nerve. AB - In this study, the effects of axotomy on heat shock protein 70 (hsp70) mRNA levels were analyzed by northern blot hybridization with a mouse-inducible hsp70 cDNA probe. The right facial nerve of adult golden hamsters was axotomized external to the skull, with the left nerve serving as sham-operated and internal control. Postoperative survival times were 0.5, 2, 6, 12, and 24 hr, with three to six animals per time point. Total RNA in the axotomized and control facial nuclear groups, dissected from the brain stem, was isolated by guanidinium thiocyanate extraction and analyzed by northern hybridization and scanning densitometry. For normalization, the blots were rehybridized with a genomic cDNA probe complementary to the 28 S rRNA. At 0.5 hr postoperative, there was a 68% induction of hsp70 mRNA levels as compared to control. This increase peaked at 2 hr postoperative with a 280% induction and declined subsequently to 160% at 6 hr, 33% at 12 hr, and -56% at 24 hr, relative to control levels. As a positive control, hyperthermia-induced hsp70 expression was established in hamster whole brain using northern blot hybridization and the mouse-inducible hsp70 cDNA probe. There was a 126% increase in hsp70 mRNA levels relative to control at 1.5 hr following hyperthermia. By 6.5 hr after the 1.5-hr hyperthermic period, there was a 40% decrease in hsp70 mRNA levels below control. The results provide the first evidence that peripheral axotomy acts as a cell stressor to induce the expression of hsp70 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601644 TI - [Evaluation of arterial pressure in the first 3 days of life in a group of healthy newborn infants weighing between 2000 and 4600 g at birth]. AB - Systolic, mean and diastolic arterial pressure (AP) was measured on the first and third days of life in a group of 270 infants born in our Hospital. The aim of this work is to see if there are modifications of AP in the first 3 days of life, and correlations between AP and weight at birth, gestational age, and different methods of delivery. Gestational age was between 34 and 42 weeks and birth weight between 2000 and 4600 grams. We excluded infants who developed any illness, those with a low Apgar score, and those whose mothers were given antihypertensive drugs. None of the examined infants received transfusion or drug which could affect the AP. Blood pressure was measured using the automatic oscillometric method. The infant's group was divided into 6 subgroups according to weight (table 1). For statistical analysis we used linear regressions and Student's "t" test. According to our data no correlation was found between birth weight and AP, nor between AP and gestational age; results obtained from other studies concerning this subject didn't agree. On the other and, we found an increase of values of AP in the third day; this agrees with the results of other Authors and is considered a consequence of the rise in peripheral vascular resistance in the postanal period. No difference was observed between the AP values of infants born by normal delivery and cesarean section. PMID- 2601642 TI - Glucose metabolism and acidosis in the metabolic penumbra of rat brain. AB - The characterization of tissue acid-base status related to the penumbral zone of increased glucose consumption surrounding a focal cerebral ischemic lesion may suggest therapeutic techniques to maximize tissue survivability from stoke. We measured local cerebral metabolic rate for glucose (1 CMRglc) and an index of brain tissue pH (pHt) concurrently and characterized their interaction in a model of focal cerebral ischemia in rats in a double-label autoradiographic study, using [14C]2-deoxyglucose and [14C]dimethyloxazolidinedione. Computer-assisted digitization and analysis permitted the simultaneous quantification of the two variables on a pixel-by-pixel basis in the same brain slices. Hemispheres ipsilateral to intravascular tamponade-induced middle cerebral artery occlusion showed areas of normal, depressed, and elevated glucose metabolic rate (as defined by an interhemispheric asymmetry index) after 2 hr of ischemia. Regions of increased 1 CMRglc showed moderate acidosis (6.87 +/- 0.05), while regions of normal glucose metabolic rate showed normal pHt (pH +/- SD = 6.98 +/- 0.05) and regions of decreased 1 CMRglc showed severe acidosis (6.69 +/- 0.11). A repeated measures analysis of variance found these values to differ from each other at the P less than 0.0005 significance level. The finding of moderate acidosis coupled with increased 1 CRMglc in the metabolic penumbra suggests that the excess protons may result from the anaerobic dissociation of ATP synthesis and hydrolysis. PMID- 2601645 TI - [Diagnostic and prognostic value of blood prealbumin in the course of neonatal infectious diseases of bacterial origin]. AB - Serum prealbumin levels were determined in a sample of newborns suffering from infectious diseases of bacterial origin. The diagnostic and prognostic significance was assessed. PMID- 2601646 TI - [Usefulness of protein C in the early diagnosis of acute infection in newborn infants at risk]. AB - The serum concentration of protein C reactive (PCR) in preterm and term children was assessed on the first, fifth, eighth and fifteenth day of life. The data obtained show that in all cases characterised by PCR values higher than 10 mg/l on the first day of life a serious infectious pathology was present which required antibiotic treatment, monitored by subsequent PCR samplings. In all cases in which PCR was negative on the first day of life and in later samples, none had presented infectious pathologies. Analysis of the results showed that so called borderline values (greater than 2 mg/l less than 10 mg/l) were present in some newborns at risk for the development of infectious pathologies. These children were subjected to antibiotic therapy as prophylaxis and in subsequent samples PCR became totally negative. PMID- 2601647 TI - [Mothers and infants as initiators of interaction in several mother/child pairs (2-4 months]. AB - The aim of this research is to show the main social patterns in five mother infant dyads (3 males and 2 females), observed in their families (48 sessions 8/16 weeks). The maternal patterns Speaking to, Smiling at, Touching directed to infants present significant correlations in our Ss (rs Spearman less than 0.01 p less than 0.001). Infants are active initiators in Looking at/ Smiling by mother, Vocalizing/ Smiling by mother. Moreover maternal initiatives differ significantly in Smiling at/ Looking at by infant, Smiling at/ Vocalizing by infant (t Student less than 0.01 p less than 0.001). PMID- 2601648 TI - [Surveillance of congenital malformations. Experiences in 1986-1987]. AB - Epidemiological data on the congenital malformations detected in 8,723 newborns over a two year period are presented. PMID- 2601649 TI - [Peroxidation of erythrocyte lipids and levels of vitamin E in red blood cells in children with chronic renal insufficiency]. AB - The tocopherol and malonyldialdeyde levels in the erythrocytes of 15 children affected by chronic renal failure, free of therapy, have been studied. Decreased levels of the former and increased of the latter were found. These data indicate red blood cell lipids peroxidation, responsible, at least in part, of the reduced red blood cell survival and of chronic anemia. PMID- 2601650 TI - [Macrolide-theophylline interaction. Experiences in pediatrics]. AB - Subjects suffering from bronchial asthma being treated with theophylline often have to be treated with an antibiotic during acute stages. The purpose of the present study is to assess to clearance variation in theophylline when a macrolide antibiotic is associated after theophyllinemia steady-state has been attained. It has been seen that macrolides interfere differently on the blood levels of theophylline. Whereas erythromycin and josamycin determine a significant reduction in theophylline clearance, Miocamycin seems not to modify this parameter significantly. PMID- 2601651 TI - [Evaluation of the usefulness of the motorcycle helmet in adolescents in Trieste]. AB - The effectiveness of the motorcycle helmet was assessed in 359 accidents involving adolescents under 16 in the Trieste area in 1985-88. Comparison of the 18 months preceding and following the introduction of the law revealed that helmet use significantly reduced the number and gravity (as objectively assessed using the Abbreviated Injury Scale) of cranial and facial injuries but made no significant difference to other areas. The 70-80% reduction in head injuries also significantly reduced the incidence of multiple injuries and hospital admissions. The effectiveness of the helmet demonstrated in this study primarily concerned with motorcycle accidents in urban areas suggests that it should now also be made obligatory for those currently exempt. PMID- 2601652 TI - [Frontal electromyography-biofeedback therapy in spasmodic torticollis in children]. AB - A case of spasmodic torticollis in childhood, treated with EMG-BFB frontalis, is reported. Our results demonstrate a rapid improvement up to remission of the disorder. Finally, the possibility of a generalization of frontal EMG-BFB to other muscles is discussed. PMID- 2601653 TI - [Gastro-esophageal reflux and asthma. Clinical experience]. AB - Gastroesophageal reflux (GER) may contribute to the persistence of asthma and may be triggered and/or exacerbated by treatment with bronchodilatory and cortisone drugs. For this reason, GER should be suspected in patients with asthma non responsive to treatment. In fact in this series 24 hour pH monitoring revealed GER in 7 out of 9 (77%) patients with persistent asthma. The use of a personally developed diagnostic protocol permitted the identification of various situations in 4 patients who completed the study: one coincidental association, one GER caused by theophylline and constituting the main cause of the bronchial obstruction. PMID- 2601654 TI - [10 families with benign familial hematuria. Considerations on prevalence, genetics and clinical and urine characteristics]. AB - We studied 10 families in which 115 members showed isolated microscopic hematuria without nephritis and impairment of renal function. All the affected members were completely asymptomatic and normal on physical and laboratory examination and therefore diagnosis of benign familial hematuria (BFH) was made. In these families BFH was inherited as an autosomal dominant trait with incomplete penetrance and variable expressivity. A linkage between BFH and ABO and Rh genes was excluded. PMID- 2601655 TI - [Enuresis in children. Diagnostic assessment and treatment]. AB - Many theories on the etiology of enuresis have been suggested, including psychogenic, structural abnormalities, dysfunctional aspects. The study consisted of 95 children with primary enuresis (35 girls, 60 boys). 58% of patients presented with enuresis plus evidence of voiding dysfunction. Patients with pure nocturnal enuresis were 17%. 42% of children have normal bladder on urodynamic testing. Anticholinergic medication was effective in children with voiding dysfunction. The base line treatment program, in children with normal urodynamic studies, included psychotherapy, medications, bladder training. Authors present their experience and results of treatment. The usefulness of urodynamic assessment in children with only nocturnal enuresis is discussed. PMID- 2601656 TI - [Monosomy 5 (-5), deletion of the long arm of chromosome 6 (6q) and acquisition of a chromosome 21 (+21) in a boy with acute leukemia at high-risk]. AB - The chromosomal abnormality 6q-, associated with acute lymphatic leukemia, is often found both in T cell form and in non T non B cell forms. The absence of chromosome -5, frequently associated with acute non-lymphatic leukemia of the adult, has been rarely found in the acute non-lymphatic leukemia of the child. Trisomy of chromosome 21 is the most associated with acute non-lymphatic leukemia of the adult, has been rarely found in the acute non-lymphatic leukemia of the child. Trisomy of chromosome 21 is the most frequent alteration found in children and adult with acute lymphatic leukemia. In a child (aged 7) affected by acute lymphatic leukemia the karyotype analysis showed simultaneously the presence of the 3 above mentioned abnormalities. It will be important to evaluate later on how the association of monosomy 5 with the deletion of chromosome's 6 long arm and with an acquired chromosome 21, the last two being indexes of a favourable prognosis, can influence the clinical course of the disease. PMID- 2601657 TI - [Apple-peel syndrome. A clinical case report and therapeutic considerations]. AB - A recently observed case of proximal jejunal atresia with apple-peel syndrome and associated multiple ileal atresia is reported. Some clinical and anatomopathological features are pointed out. Surgical techniques and medical care are analysed. PMID- 2601658 TI - [Craniostenosis. Analysis of 161 cases surgically treated during the first year of life]. AB - One hundred-sixty-one cases of children operated on for craniostenosis in the first year of life at the Neurosurgical Department of the Catholic University of Rome in the period 1982-1986 are presented. The average age at diagnosis was 6 months and at operation 7.4 months. The patients considered in the present study were subdivided into two groups according to the prevalent involvement of sagittal suture or of the anterior sutural group (coronal metopic, spheno-frontal and spheno-palatine sutures). In fact, these two groups differ considerably not only in the characteristics of the pathological process of early fusion of the cranial sutures, but also in the technique required for surgical correction. Four children with premature fusion of all cranial sutures are considered separately. Congenital malformations of the bone structures or changes in ocular motility were presented in 7.9% of 63 patients with sagittal craniostenosis and in 14.7% of the group with premature fusion of the anterior cranial sutures. Surgical correction (linear craniectomies extended to the cranial base for the group with sagittal craniostenosis, craniectomies with advancement of the supraorbital margin and rotation of the bone operculum for the group with anterior craniostenosis) proved satisfactory in the great majority of cases. Postoperative morbidity was particularly low. Apart from postsurgical anaemia which required blood transfusion on the third day in 15.5% of operated patients, the only complications were transitory hyperpyretic states observed in 6.2% of cases. Only one child died for reasons related to the surgical procedure. The low postoperative mortality (0.6% of cases) and the low percentage of bone pathology recurrence (7.4%) compared with the results of other series involving older children, seem to indicate that the early surgical correction of bone malformations does not bear additional risk for the patient, permitting at the same time normal functional development of the brain and a more gradual morphological remodelling of the skull. PMID- 2601659 TI - [Bronchography in children. Methodologic, statistical and functional findings]. AB - The value of bronchography in the various respiratory diseases of childhood is examined. After a brief critical review of the historical development of bronchography, 10 cases encountered in the Pneumology Unit of Regina Margherita Children's Hospital, Turin are examined in order to compare the indications to and results of bronchography. In the light of the results obtained guidelines for the selection of bronchography as a diagnostic procedure are presented, specifying the situations in which stratigraphy, CAT scans or NMR are not adequate substitutes and suggesting what should be the current role of bronchography in paediatrics. PMID- 2601660 TI - [Mineral bone content in full-term infants. Effect of anthropometric characteristics]. AB - The clinical importance of the measurement of bone mineral content (BMC) in fullterm infants by photon absorptiometry relies on a comparatively narrow normative range that is necessary requisite to interpret the data from a single child. In the attempt to reduce the artifactual scattering of data, it was undertaken a normative study to control all variables that might affect BMC at birth. Thus, growth parameters and birth season (as an index of maternal vit. D status) were related to BMC, Bone Width (BW) and the considered growth parameters did not show any significant difference related to sex and birth season. Thus, all data were analyzed together. It appears that BMC at birth in fullterm infants averaged 92.2 +/- 14.6 mg/cm. BMC did not correlate with skeletal length, crown length and gestational age in the considered range. Conversely, significant correlation were found between BMC and BW and between BMC and body weight. We conclude that: a) birth season and sex do not affect bone mineralization in fullterm infants, b) any comparison among BMC should be established within populations homogeneous for weight and BW. PMID- 2601661 TI - [Allergy to Hymenoptera venom in children. Diagnosis and therapy]. AB - We studied 52 children, 3 to 15 years of age, suffering from allergic reactions following Hymenoptera stings. The diagnosis of allergy was based on history, results of skin tests and RAST performed by purified venoms of Apis mellifera, Vespula species and Polistes species. The history of children with multiple stings of the same insect showed an essential favourable prognosis, thus suggesting to submit to specific immunotherapy only children with severe reactions. For these patients it is necessary to perform therapy only in specialized Centres, because of the high frequency of adverse reactions which we observed in 33% of our treated patients. PMID- 2601662 TI - [Importance of a particular formula of soybean milk without S2 globulin, in the treatment of allergy to cow's milk proteins]. AB - Replacing cow's milk with a soybean milk is one of the first measures which are commonly taken with babies suffering from cow's milk protein allergy. Unfortunately soybean can induce sensitization, too, with a variable percentage (ranging from 12 to 80%) according to the different Authors, due to the presence of allergenic proteins, among which the most important one seems to be S2 globulin. An excellent tolerability has been reported in a study carried out with 20 babies suffering from cow's milk protein allergy besides a good palatability of the product with a solution of symptoms in 87.3% of the cases. Only in 16.7% of the treated babies intolerance has been reported and therefore we can conclude that soybean milk has proved to be an excellent substitute of cow's milk in babies suffering from cow's milk protein allergy. PMID- 2601663 TI - [Description of a case of Meckel's diverticulum and chronic anemia in a 4-year old boy]. AB - The case of a boy of 4 years 6 months suffering from Meckel's diverticulum (M.D.) and chronic anaemia is reported. The patient presented no evident sign of bleeding of the mucosa or of other sites. Admitted to the Paediatric Clinic for severe anaemia, he underwent numerous clinical and laboratory investigations that revealed the presence of a bleeding M.D. This was removed surgically and in a comparatively short time (about 3 months), the haematic picture normalized, with manifest benefit to the child. PMID- 2601665 TI - On changing the mass consciousness. Interview by Richard L. Reece. PMID- 2601664 TI - Leading the charge to healthy habits. PMID- 2601666 TI - On not blowing smoke. Interview by Richard L. Reece. PMID- 2601667 TI - The community as the patient. PMID- 2601668 TI - Promoting health in the heartland. PMID- 2601669 TI - A controlled trial to implement smoke-free hospitals. AB - Hospitals would logically become leaders if the nation is to accept former Surgeon General C. Everett Koop's challenge to make its public institutions smoke free by the year 2000. We tested whether printed materials, workshops, newsletters, and consultations could increase both the number of smoke-free hospitals in a state and the rate at which they became smoke-free. All acute-care hospitals in Minnesota (n = 166) were compared to a sample of 51 acute-care hospitals in a reference area, western Wisconsin, before and after a one-year campaign. While 2.4% of the hospitals in Minnesota were smoke-free before the campaign, none of the hospitals in the reference area sample was smoke-free at this time. Both areas experienced a significant increase in the proportion of hospitals that became smoke-free during the year--30.7% of the Minnesota hospitals and 15.7% of the hospitals in the reference area sample (p less than .01) were smoke-free after the one-year campaign--and the campaign did appear to marginally increase the rate of adoption in Minnesota over that of the reference area (p = .08). The results of this study indicate that smoke-free hospitals are feasible and that a statewide initiative can facilitate the hospitals' decision to become smoke-free. PMID- 2601670 TI - Minnesota enacts a brain death law. PMID- 2601671 TI - Anti-pneumonia AIDS drug. PMID- 2601672 TI - Medical care in a changing health care environment. PMID- 2601673 TI - Topical zinc and delayed hypersensitivity responsiveness. AB - The ability of topical zinc to enhance the DHR to skin test antigens may be a simple method of evaluating functional zinc status. Additional testing is required to determine the sensitivity and specificity of this technique. In addition to zinc, other nutrient deficiencies such as protein deficiency may suppress DHR. Because of this and because of the variability among individuals in degree of reactiveness, each patient should serve as his/her own control, with zinc-treated and nontreated skin test sites being evaluated simultaneously. PMID- 2601674 TI - Accounting for training. PMID- 2601675 TI - Strangers among strangers: clients and health practitioners in health care settings. AB - This paper describes a course assignment designed to sensitise nursing students to the meaning of the experience of being a stranger in a cultural setting where the norms and rules for behaviour are unclear or essentially unknown. This experience alerts the student to be aware of the possibility that people's usual responses to strangers in unfamiliar settings, may be an inhibitory factor in the development of a therapeutic relationship between the nurse, and other health practitioners, and their clients. Discussion is centred on the student learning which occurs, both personally and professionally, in the conduct of this assignment. PMID- 2601676 TI - Collaboration projects between nursing education and nursing service: a case study. AB - Collaboration refers to a variety of efforts to blend nursing education and nursing service. A regional planning agency in Southwestern Pennsylvania assumed a strategic role in developing a collaboration action plan which was expressed in three pilot demonstration projects involving an associate degree, a baccalaureate, and a diploma program with their respective service partners. The purpose of this 2 year evaluation case study was to assess the extent to which the three demonstration projects met their stated goals and objectives. The sample was self selected from the pool of nursing education programs and hospitals in the ten county Southwestern Pennsylvania planning region based on willingness to participate and compliance with project criteria. Suchman's model was used as the framework from which to evaluate the projects. Program participants indicated that the project resulted in enhancement of the school agency relationship, more confident, competent students, and increased enthusiasm among staff who perceived they had a stake in the educational process. This study has implications for nursing practice, education and research. The implementation of well-planned collaboration projects yield many benefits, chief of which is enhanced co-operation between nursing service and nursing education. The benefits are valuable for international colleagues who may be testing out similar approaches in their respective countries. PMID- 2601677 TI - Population-focused practice: introduction to baccalaureate-level nursing students. AB - This article describes a clinical nursing experience which introduces baccalaureate students to population-focused practice in the community. The importance of such practice in community health nursing is discussed as is the rationale for including it at the undergraduate level. An overview of how the experience fits within the baccalaureate nursing curriculum is presented. Individual and group student responsibilities are outlined, explaining the structure of this nursing experience. Student projects with two groups--the well elderly and the school-aged are described to illustrate the clinical experience. Finally, an evaluation of the experience is presented which indicates that it has benefits for clients, community health nurses, students and faculty. PMID- 2601678 TI - What is an interpersonally skilled person?: a repertory grid account of professional nurse's views. AB - This study sought to identify how a group of professional nurses viewed the notion of an 'interpersonally skilled person'. Using a modified repertory grid approach, we asked 21 professional nurses to elicit eight bi-polar constructs relating to an 'interpersonally skilled person'. A total of 168 constructs was produced and these were analysed into different content areas. In addition, respondents were asked to rate themselves against the set of constructs that they, themselves, had elicited. Three levels of findings are offered in this study: 1) the content of the constructs that were elicited 2) the distribution of the constructs within these content areas 3) the discrepancies that were found between self and ideal self elements The findings indicated that the nurses in this study tended to view the interpersonally skilled person more in terms of personal qualities than in terms of identifiable skills. They also tended to identify themselves as deficient in many of the qualities that they elicited. The study has implications for teaching interpersonal skills and these are discussed in this report. PMID- 2601679 TI - Changes in nurse education and the facilitation of nursing research: an exploratory study. AB - This study is concerned with exploring nurses' attitudes and knowledge of nursing research, together with their perception of research priorities. A sample was drawn from five nursing groups, these being Assistant Directors of Nursing Services (ADNS), Ward Sisters, Student Nurses undertaking a conventional educational programme, students undertaking the Diploma in Professional Studies in Nursing Course (DPSN) and student nurses undertaking an ENB pilot scheme in general nursing. Whilst the results suggest that all groups held favourable attitudes towards nursing research, significant differences emerged with respect to knowledge of such research and perception of research priorities. Of particular interest are the differences observed in comparing the nursing groups who have had experience of higher education with those who have not. The former generally had more positive attitudes, a better knowledge base and clearer priorities for nursing research. Given that many countries now provide nurse education in such centres and that nurse education in the United Kingdom is steadily moving in this direction, the results are important in suggesting some of the benefits which can accrue from collaboration between schools of nursing and centres of higher education. PMID- 2601680 TI - The community hospital--an underused resource for learner education. AB - Only a small number of learners in this country spend any of their training period working with patients in Community Hospital despite their importance as an element of local Primary Care. This article describes how one School of Nursing and the associated Community Hospitals, situated in a predominantly rural area, were involved in the preparation for learner placements for Parts 1 and 5 of the Professional Register. It then continues with the aims of the placements and some of the evaluations by the trained staff, and the learners involved. Finally, the author discusses the programme and suggests that with some modifications the Community Hospital scheme has a unique contribution to offer learners as a resource in Nurse Education both now and in the implementation of Project 2000. PMID- 2601681 TI - Curriculum evaluation. AB - Curriculum evaluation is an essential phase of curriculum development. Through evaluation a faculty discovers whether a curriculum is fulfilling its purpose and whether students are actually learning. The purpose of this manuscript is to describe the implementation of a formative evaluation used by faculty members of a baccalaureate nursing program. PAIREDAR, a three phase generic model, was utilised to conduct this formative evaluation. The definition and description of this model are included. The process used by the evaluation team within the framework of the model is described in a step by step fashion. Faculty and student interview question sets and a sample course evaluation worksheet are presented. PMID- 2601682 TI - Professional judgement and nurse education. AB - This paper discusses some issues related to the difficulties faced by the professionals who are required to assess a student nurse's competence to practice. PMID- 2601683 TI - An experience of transition from a medical model to a nursing model in nurse education. AB - The major focus of the paper will be on the change from a curriculum content which was primarily medically dominated to one in which a nursing model is clearly identified. The implications of such changes for nurse teachers, clinical staff and student nurses are discussed. PMID- 2601684 TI - Human liver thermostable phenol sulfotransferase: photoaffinity labeling with 2 iodo-4-azidophenol. AB - Phenol sulfotransferase (PST) catalyzes the sulfate conjugation of phenolic drugs, neurotransmitters, and xenobiotic compounds. Human tissues contain at least two forms of PST, which differ in their substrate specificities, inhibitor sensitivities, physical properties, and regulation. One form of the enzyme is thermostable (TS) and catalyzes the sulfate conjugation of micromolar concentrations of "simple" phenols. The other form of PST is thermolabile and catalyzes the sulfate conjugation of micromolar concentrations of dopamine and other phenolic monoamines. Quantitative structure-activity relationship (QSAR) analyses of substrate kinetic data obtained with purified human liver TS PST made it possible to design a photoreactive substrate for this form of the enzyme. Because of the very high affinity of TS PST for 2-halogenated phenols, 2-iodo-4 azidophenol (IAP) was synthesized and tested for this purpose. The Km predicted for IAP on the basis of QSAR analysis was 95 nM. The apparent Km determined experimentally was 52 nM. UV irradiation of partially purified human liver TS PST in the presence of [125 I]IAP and 3'-phosphoadenosine-5'-phosphosulfate, the sulfate donor for the reaction, resulted in the radioactive labeling of two proteins, with molecular weights of 32,000 and 34,000, by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Inhibitors of the reaction catalyzed by TS PST, including 2,6-dichloro-4-nitrophenol-3'-phosphoadenosine- 5'-phosphate and NaCl, as well as 2-iodophenol, a competing substrate, inhibited the photolabeling of both of these proteins by [125I]IAP in a concentration-dependent fashion. Partially purified TS PST was then radioactively labeled with [125]IAP and was subjected to gel filtration high performance liquid chromatography to verify that the photo-affinity-labeled proteins detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis coeluted with TS PST enzyme activity. Photoaffinity labeling of TS PST will be useful in studies of the molecular characteristics of the protein and its active site, as well as in the purification of this important drug-metabolizing enzyme. PMID- 2601686 TI - Apparent competition between ATP and the potassium channel opener RP 49356 on ATP sensitive K+ channels of cardiac myocytes. AB - The mechanism whereby RP 49356, a novel potassium channel opener, activates ATP sensitive K+ channels (K+-ATP channels) in isolated cardiac cells was investigated with the patch-clamp technique. When directly applied onto the inner face of an inside-out membrane patch, RP 49356 (300 microM) had no effect on K+ channels opened in an ATP-free solution. In contrast, the same concentration of the drug reactivated K+-ATP channels that had experienced spontaneous "run-down" of their activity following long recording periods. In cell-attached experiments, externally applied RP 49356 (300 microM) opened K+-ATP channels at 35 degrees in spite of the high intracellular ATP concentration, which was sufficient to prevent channel openings in the absence of the drug. In control conditions, the dose-response relation for ATP closing the channels had a Hill coefficient of 2.37 and a half-inhibition concentration of 56 microM. With 30 microM RP 49356 present in the intracellular medium, the slope factor of this relation was unchanged but the curve was shifted to the right, with a half-inhibition concentration of 515 microM. Conversely, the dose-response relation of RP 49356 activating K+-ATP channels was shifted to the right in a parallel manner under the influence of increasing concentrations of ATP. It is concluded that RP 49356 acts on cardiac K+-ATP channels by decreasing their sensitivity to ATP. Our results are consistent with an apparent competition between ATP and RP 49356. PMID- 2601685 TI - Distinct requirements for activation at CCK-A and CCK-B/gastrin receptors: studies with a C-terminal hydrazide analogue of cholecystokinin tetrapeptide (30 33). AB - We describe here the properties of tert-butyloxycarbonyl-Trp-Leu-Asp-Phe-NHNH2 (A 57696), a C-terminal hydrazide analogue of tert-butyloxycarbonyl-CCK4 (Boc-Trp Met-Asp-Phe-NH2), at four cholecystokinin (CCK) receptor-bearing tissues, the guinea pig pancreas and gall bladder (Type A), guinea pig cortex (Type B), and NCI-H345 cells, a human small cell lung cancer cell line that expresses CCK B/gastrin receptors. Using 125I-Bolton-Hunter-cholecystokinin octapeptide (26-33) (125I-Bolton-Hunter-CCK8) as the radioligand, A-57696 was found to be selective for cortical CCK-B receptors (IC50 = 25 nM), compared with pancreatic CCK-A receptors (IC50 = 15 microM). A-57696 behaved as a competitive antagonist in reversing CCK8-stimulated pancreatic amylase secretion and phosphoinositide breakdown. By Schild analysis, its Kd was determined to be 4.7 and 6.8 microM in amylase and phosphoinositide assays, respectively. A-57696 (100 microM) did not elicit gall bladder contraction, and it inhibited contractions induced by CCK8. The Kd of A-57696 at gall bladder CCK-A receptors was 19 microM. In contrast, A 57696 behaved as a partial agonist (80% of maximal CCK8 response) in stimulating calcium mobilization at CCK-B/gastrin receptors on NCI-H345 cells. A-57696 and CCK8 inhibited each other in calcium mobilization experiments utilizing the fluorescent dye Indo-1. Stimulatory actions of CCK8 and A-57696 were reversed by the CCK-B-selective (R)-L-365,260 (100 nM), whereas at the same concentration, the CCK-A-selective (S)-L-365,260 was ineffective. Binding studies using 125I Bolton-Hunter-CCK8 and 125I-gastrin indicated that binding sites labeled by these two ligands displayed similar affinities for CCK8, desulfated CCK8, gastrin, A 57696, and both enantiomers of L-365,260. A-57696 represents a new class of CCK-A peptide antagonist at guinea pig pancreas a new class of CCK-A peptide antagonist at guinea pig pancreas and gall bladder. Its contrasting functional activities at guinea pig CCK-A and CCK-B/gastrin receptors in a human tumor cell demonstrate that, in addition to the previously described differences in binding specificity for selective agonists and antagonists, CCK-A receptors and CCK-B/gastrin receptors have different requirements for activation. PMID- 2601687 TI - H-7, a protein kinase C inhibitor, inhibits phorbol ester-caused ornithine decarboxylase induction but fails to inhibit phorbol ester-caused suppression of epidermal growth factor binding in primary cultured mouse epidermal cells. AB - 12-O-tetradecanoylphorbol-13-acetate (TPA) induced ornithine decarboxylase (ODC) and suppressed 125I-epidermal growth factor (EGF) binding in primary cultured mouse epidermal cells. TPA (30 nM)-caused ODC induction was almost completely blocked by 30 microM H-7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine], a well known protein kinase C inhibitor, but the same concentration of H-7 failed to restore the 125I-EGF binding suppressed by TPA (10 nM). On the other hand, sphingosine, another protein kinase C inhibitor, blocked not only TPA-caused ODC induction but also TPA-caused suppression of 125I-EGF binding. Concentration response curves of sphingosine for these two TPA-caused cellular responses were almost identical. 1,2-Diacylglycerols such as 1,2-dioctanoylglycerol (30-300 microM) and 1-oleoyl-2-acetylglycerol (OAG) (30-300 microM) mimicked TPA actions. Similar to the case of TPA, suppression of 125I-EGF binding by OAG was barely inhibited by H-7, whereas sphingosine was more effective in inhibiting the OAG caused suppression of 125I-EGF binding than was H-7. In TPA (50 nM)-pretreated epidermal cells, TPA (10 nM) failed to suppress 125I-EGF binding. H-7 (30 microM) did not affect TPA (30 nM)-caused translocation of protein kinase C. These results clearly demonstrate the differential inhibition by H-7 of the TPA-caused cellular responses and indicate that TPA-caused suppression of 125I-EGF binding to epidermal cells is mediated through protein kinase C function, which is barely inhibited by H-7. PMID- 2601688 TI - Metabolism of prazepam by rat liver microsomes: stereoselective formation and N dealkylation of 3-hydroxyprazepam. AB - The metabolism of prazepam (7-chloro-1-(cyclopropylmethyl)-1,3-dihydro-2H-1, 4 benzodiazepin-2-one) (PZ) was studied using liver microsomes prepared from untreated, phenobarbital (PB)-treated, and 3-methylcholanthrene (3MC)-treated male Sprague-Dawley rats. Relative rates of PZ metabolism by liver microsomes prepared from rats were PB-treated greater than untreated greater than 3MC treated. Metabolites of PZ were separated by normal phase high performance liquid chromatography and the relative amounts of major metabolites were found to be N desalkylprazepam (also known as N-desmethyldiazepam and nordiazepam) greater than 3-hydroxy-PZ (3-OH-PZ) greater than oxazepam. Enantiomers of 3-OH-PZ were resolved by high performance liquid chromatography on an analytical column packed with Pirkle's chiral stationary phase, (R)-N-(3,5-dinitrobenzoyl)phenylglycine covalently bonded to spherical particles of gamma-aminopropylsilanized silica. 3 OH-PZ formed in the metabolism of PZ by liver microsomes prepared from rats was found to have 3R/3S enantiomer ratios of 84:16 (untreated), 85:15 (PB-treated), and 84:16 (3MC-treated), respectively. Relative rates of N-dealkylation of PZ by three rat liver microsomal preparations were PB-treated greater than untreated greater than 3MC-treated. N-Dealkylation of 3-OH-PZ by rat liver microsomes was substrate enantioselective; the 3S-enantiomer was N-dealkylated faster than the 3R-enantiomer. The results indicated that both C3-hydroxylation of PZ and N dealkylation of 3-OH-PZ catalyzed by rat liver microsomes were stereoselective, resulting in the formation of a 3-OH-PZ highly enriched in the 3R-enantiomer. PMID- 2601689 TI - Mutagenicity of dimethyl heteroaromatic triazenes in the Ames test: the role of hydrophobicity and electronic effects. AB - The mutagenicities of five heterocyclic 3,3-dimethyltriazenes have been evaluated in the Ames test. The octanol-water partition coefficients (P) for these triazenes have been measured, and their electron distributions and molecular orbital energies were calculated using the MNDO semiempirical molecular orbital method. Molecular structures of three triazenes have been determined using X-ray crystallography. The mutagenicities of these five triazenes, which range from nearly inactive to very highly mutagenic, are well predicted by quantitative structure-activity relationships that had been derived previously for the mutagenicity of aryltriazenes. The form of these equations indicates that more hydrophobic and more electron-rich triazenes are more active in the Ames test. This supports the hypothesis that the ease of initial triazene activation by cytochrome P-450 governs the mutagenicity of these compounds. PMID- 2601690 TI - Response of bone marrow stromal cells to adipogenic antagonists. AB - Adipocytes constitute a major part of the bone marrow stroma in vivo and may play an active role in lymphohematopoiesis. Earlier studies had shown that the bone marrow stromal cell clone BMS2 was capable of adipocyte differentiation in vitro, in addition to its well-defined ability to support B lymphopoiesis. We now demonstrate that the process of adipogenesis in this functional bone marrow stromal cell clone can be inhibited by the cytokines interleukin-1 alpha, tumor necrosis factor, and transforming growth factor beta. Exposure of preadipocyte BMS2 cells to these agents blocked the induction of adipocyte differentiation as assessed by morphologic criteria and analysis of the neutral lipid content. Both interleukin-1 alpha and tumor necrosis factor elicited a rapid transient elevation in the steady-state mRNA levels of c-fos, c-jun, and JE. When added to differentiated adipocytes, the three cytokines continued to act as adipogenic antagonists. This was indicated by concentration- and time-dependent decreases in the activity of an adipocyte-specific enzyme, lipoprotein lipase. These changes in enzyme activity correlated directly with a decrease in steady-state levels of lipoprotein lipase mRNA. Another RNA marker of adipocyte differentiation (adipsin) was less influenced by the adipogenic antagonists. This may reflect the longer half-life of this mRNA transcript compared with those of lipoprotein lipase. Our results dramatically demonstrate that the differentiation state of bone marrow stromal cells can be modulated by exogenous factors in vitro. It is also the first report that transformation growth factor beta regulates the activity of lipoprotein lipase. These data suggest potential physiologic actions for these cytokines in vivo within the overall context of lymphohematopoiesis. PMID- 2601691 TI - Mutations in the RB1 gene and their effects on transcription. AB - Inactivation of both alleles of the RB1 gene during normal retinal development initiates the formation of a retinoblastoma (RB) tumor. To identify the mutations which inactivate RB1, 21 RB tumors isolated from 19 patients were analyzed with the polymerase chain reaction or an RNase protection assay or both. Mutations were identified in 13 of 21 RB tumors; in 8 tumors, the precise errors in nucleotide sequence were characterized. Each of four germ line mutations involved a small deletion or duplication, while three somatic mutations were point mutations leading to splice alterations and loss of an exon from the mature RB1 mRNA. We were unable to detect expression of the mutant allele in lymphoblasts of three bilaterally affected patients, although the mutation was present in the genomic DNA and transcripts containing the mutations were obvious in the RB tumors in the absence of a normal RB1 allele. The variations in the level of expression of mutant transcripts suggest deregulation of RB1 transcription in the absence of a functional RB1 gene product. PMID- 2601692 TI - Identification of a cis-acting element controlling induction of early gene expression in Dictyostelium discoideum. AB - Using a new promoter analysis transformation vector for Dictyostelium discoideum (PAV-CAT), we have defined cis-acting elements in the promoter of the cyclic AMP induced early-expressed gene A11H2, which encodes an alpha-fucosidase-related protein (A. Muller-Taubenberger, M. Westphal, A. Noegel, and G. Gerisch, FEBS Lett. 246:185-192, 1989). Sequences responsible for developmentally regulated gene induction could be separated from the basal promoter that conferred low levels of transcriptional activity. By gel shift experiments, we present evidence that the cis-acting element is the target of a trans-acting factor that by itself is subject to developmental regulation. PMID- 2601693 TI - Mechanism of suppression of the long terminal repeat of Moloney leukemia virus in mouse embryonal carcinoma cells. AB - Sequence-specific DNA-binding proteins that bind to the long terminal repeat (LTR) of Moloney leukemia virus in undifferentiated and differentiated mouse embryonal carcinoma (EC) cells were identified by gel retardation assay. The proteins that bind to the CCAAT box were present in both undifferentiated and differentiated EC cells. The amounts and the number of species of the proteins that bind to the enhancer and the GC-rich region were far lower in undifferentiated EC cells than in the differentiated counterparts. These proteins were supposed to be transcriptional activators. Proteins that bind upstream of the enhancer, namely, the -352 to -346 region and the -407 to -404 region, were identified. These proteins were designated the embryonic LTR-binding protein (ELP) and the LTR-binding protein, respectively. The ELP was present only in undifferentiated EC cell lines. The LTR-binding protein was detected in all cell lines tested. The mechanism of suppression of the LTR was investigated by the chloramphenicol acetyltransferase assay. The enhancer and the GC-rich region of the LTR functioned poorly in undifferentiated cells. When eight copies of ELP binding sequences were inserted upstream of the enhancer region, expression of the chloramphenicol acetyltransferase gene was reduced about threefold in ECA2 cells. From these data, we concluded that two mechanisms, the shortage of activator proteins and the presence of a negative regulatory protein (ELP), are involved in the suppression of the LTR in undifferentiated EC cells. PMID- 2601694 TI - Multiple components are required for sequence recognition of the AP1 site in the gibbon ape leukemia virus enhancer. AB - At least two subunits contributed to the formation in vitro of a specific complex binding to the AP1 consensus sequence (TGAGTCA) in the gibbon ape leukemia virus (GALV) enhancer in MLA144 cells. This complex can be dissociated on a monomeric GALV oligonucleotide affinity column. One protein, termed the core protein, was retained on the oligonucleotide affinity column. The second protein flowed through the oligonucleotide affinity column and, when alone, did not bind to DNA; however, when present with the core protein, it bound strongly and very specifically to the GALV sequence. MLA144 cells contained only trace amounts of c fos and c-jun by immunoblot analysis, suggesting that the proteins specifically binding to the GALV AP1 site were distinct from c-fos and c-jun. In addition to the major complex that recognized the GALV element, MLA144 cells contained a minor complex that is chromatographically different from and antigenically related to c-fos. The factor in the flowthrough complemented a human T-cell nuclear extract (Jurkat cell line), which, when alone, had no assayable complex that specifically bound to the GALV enhancer; this complementation gave rise to a specific complex similar to that seen in MLA144 cells. Together, these results suggest that the GALV enhancer can interact with multicomponent protein complexes in a cell-line-specific manner. PMID- 2601695 TI - Expression of the MyoD1 muscle determination gene defines differentiation capability but not tumorigenicity of human rhabdomyosarcomas. AB - Several human rhabdomyosarcoma cell lines, cultured primary tumor explants, and biopsies of tumor and normal skeletal muscle tissue expressed a 2.0-kilobase transcript that hybridized to the mouse muscle determination gene MyoD1. This transcript was found in tumor cell lines and primary explants that developed multinucleated myotubes but was absent in Wilms' tumors or cell lines and primary explants that developed multinucleated myotubes but was absent in Wilms' tumors or cell lines derived from other mesenchymal tumor cell types. Expression of the human homolog of MyoD1 therefore can define a tumor as a rhabdomyosarcoma. Transfection of the mouse MyoD1 gene into the human rhabdomyosarcoma cell line RD increased the ability of the tumor cells to differentiate into multinucleated myotubes and enhanced myosin heavy-chain gene expression but did not decrease tumorigenicity in nude mice. PMID- 2601696 TI - The rat albumin promoter is composed of six distinct positive elements within 130 nucleotides. AB - No fewer than six different positive regulatory elements concentrated within 130 base pairs constitute the rat albumin promoter, which drives highly tissue specific transcription in rat hepatoma cells in culture. Inactivation of each element led to a decrease in transcriptional efficiency: from upstream to downstream, 3- to 4-fold for distal elements III and II, 15-fold for distal element I, and 50-fold for the CCAAT box and the proximal element (PE). Three of these elements, distal elements III and II and, more crucially, the PE, were found to be involved in the tissue-specific character of transcription, with an additional negative regulation possibly superimposed at the level of the PE. Finally, our mapping of these regulatory elements in vivo entirely coincided with footprint data obtained in vitro, thereby allowing the tentative assignment of specific factors to the effects observed in vivo. PMID- 2601697 TI - Isolation and characterization of an extragenic suppressor of the low-density lipoprotein receptor-deficient phenotype of a Chinese hamster ovary cell mutant. AB - ldlC cells are low-density lipoprotein (LDL) receptor-deficient Chinese hamster ovary cell mutants which express pleiotropic defects in Golgi-associated glycosylation reactions. The dramatically reduced stability of the abnormally glycosylated LDL receptors in ldlC cells was shown to be due, in part, to rapid proteolysis and release of a large extracellular fragment of the receptor into the medium. A set of spontaneously arising LDL receptor-positive revertants of ldlC cells has been isolated. One of these, RevC-13, exhibits the glycosylation defects characteristic of the original ldlC mutant, suggesting that restoration of receptor activity was due to extragenic suppression. This suppression was due to a dramatic increase in the rate of LDL receptor synthesis rather than to an increase in the stability of the abnormally glycosylated receptors. Increased receptor synthesis was not due to receptor gene amplification. The increased LDL receptor activity was subject to normal sterol regulation. Analysis of the RevC 13 extragenic suppressor activity in a series of hybrid cells showed that RevC-13 suppression was a codominant trait that acted in cis to the LDL receptor structural gene (ldlA). Thus, the extragenic suppression in RevC-13 cells has defined a genetic element which is either part of or linked to the LDL receptor structural gene and which can control LDL receptor expression. PMID- 2601698 TI - The 216-nucleotide intron of the E1A pre-mRNA contains a hairpin structure that permits utilization of unusually distant branch acceptors. AB - A recently characterized 216-nucleotide intron-splicing reaction occurs within the adenovirus E1A pre-mRNA through the use of three branch acceptor sites, located at 59, 55, and 51 nucleotides from the 3' splice site. To investigate the role of the cis-acting sequence elements in the selection of such unusually distant branch sites, transcripts differing in sequence downstream of the branch sites were analyzed for in vitro splicing. Initial results suggested that secondary structure could be involved in the use of distant branch sites. The involvement of a hairpin structure, including a nine-G C-base-pair stem, was supported by the results of site-directed mutagenesis analyses. Mutations that destroyed or weakened this hairpin resulted in an inefficient splicing reaction. In contrast, complementary mutation or deletion of two bulges, which involved a restoration or reinforcement of the hairpin, resulted in a reactivation or improvement of the splicing efficiency, respectively. Therefore, we conclude that the hairpin structure shortens the operational distance between the 3' splice site and the branch acceptors and brings the branch sites into the branch permissive window, 18 to 40 nucleotides upstream of the 3' splice site. Our results confirm the importance of the constraint of distance for the splicing reaction and show that this constraint may be overcome by means of a stable hairpin formation. PMID- 2601699 TI - Degradation of linear DNA by a strand-specific exonuclease activity in Xenopus laevis oocytes. AB - Linear DNA injected into Xenopus laevis oocyte nuclei recombines with high efficiency if homologous sequences are present at overlapping molecular ends. We found that injected linear DNA was degraded by a 5'----3' strand-specific exonuclease activity during incubation in the oocyte nucleus to leave a heterogeneous population of 3'-tailed molecules. Decreasing the concentration of DNA injected increased the heterogeneity and the average rate of degradation. The 3' tails created were relatively stable; among molecules persisting after overnight incubation, many had 3' tails intact to within 10 bases of the original ends. DNA molecules that were efficient substrates for homologous recombination in oocytes were also partially degraded, leaving 3' tails. We found no evidence for other potent nuclease activities. If molecules with recessed 3'-OH ends were injected, endogenous polymerase efficiently resynthesized complementary strands before degradation of the 5' tails occurred. 3'-tailed molecules are plausible intermediates in the initiation of homologous recombination events in Xenopus oocyte nuclei. PMID- 2601700 TI - Amplified N-myc in human neuroblastoma cells is often arranged as clustered tandem repeats of differently recombined DNA. AB - Human neuroblastoma cells often carry amplified DNA encompassing the gene N-myc. Amplified N-myc has been found localized in "double minutes" in direct tumor cell preparations. In contrast, later passages carried amplified N-myc almost exclusively within a single homogeneously staining chromosomal region located at a chromosomal site different from the normal location of N-myc. We used pulsed field gel electrophoresis to define the structural arrangement of the amplified DNA. Long-range mapping was facilitated by the presence of several sites for rare cutting restriction endonucleases in the 5' region of N-myc. Amplified DNAs of different neuroblastoma cell lines were heterogeneous in size and had undergone recombination at various distances from N-myc. N-myc occupied a central position within the amplified DNA, and in no case was the coding region affected by recombination. Among neuroblastoma cells, varying proportions of amplified DNA (in some instances close to 100%) consisted of multiple tandem arrays of DNA segments ranging in size from 100 to 700 kilobase pairs. Tumor cells with low degrees of amplification revealed regions of amplified DNA in excess of 1,500 kilobase pairs without apparent rearrangement. Our observations, in concert with the cytogenetic findings, suggest a model of gene amplification which involves unscheduled DNA replication, recombination, and formation of extrachromosomal DNA followed by integration into a chromosome and subsequent in situ multiplication. The central position which N-myc occupies within the amplified sequences and the lack of recombination within the coding region of N-mc indicate that N-myc rather than other genetic information provides the selective advantage for retention of the amplified DNA. PMID- 2601701 TI - Developmental appearance of transcription factors that regulate liver-specific expression of the aldolase B gene. AB - The region from -202 to -1 of the rat aldolase B (AldB) promoter directs tissue specific transcription in vitro. Deletion of the half of this promoter distal to its origin reduced its ability for tissue-specific expression. Two protein binding sites in this distal element have been identified and characterized. One bound a factor named AIF-A, which is probably identical to previously characterized liver-specific factors HNF-1 and APF. The other, containing a CCAAT motif, bound a factor named AIF-B. These two factors were considerably enriched in liver cells compared with other cells not expressing AldB. In the liver, these two factors increased prior to the activation of the AldB gene during development. Liver-specific in vitro transcription assays indicated that the binding of both factors to their target sequences was required for AldB transcription. These results suggest that AIF-A and AIF-B are positively acting transcription factors that regulate tissue-specific and development stage specific activation of the AldB gene. PMID- 2601702 TI - Human transcription factor TFIIIC2 specifically interacts with a unique sequence in the Xenopus laevis 5S rRNA gene. AB - Transcription factor TFIIIC2 derived from human cells is required for tRNA-type gene transcription and binds with high affinity to the essential B-box promoter element of tRNA-type genes. Although 5S rRNA genes contain no homology with the tRNA-type gene B box, we show that TFIIIC2 is also required for Xenopus laevis 5S rRNA gene transcription. TFIIIC2 protected an approximately 30-base-pair (-10 to +18) region of a Xenopus 5S rRNA gene from DNase I digestion. This region, which spanned the transcription start site, included sequences that are highly conserved among eucaryotic 5S rRNA genes and have no homology with the B-box sequence of tRNA genes. Mutation of the TFIIIC2-binding site reduced transcription of the 5S rRNA gene by a factor of 10 in HeLa cell extracts. Methylation of C residues within the TFIIIC2-binding site interfered with binding of TFIIIC2. These results suggest a role of the TFIIIC2-binding sequence in 5S rRNA gene transcription. In addition, the 5S rRNA gene binding site and the tRNA type gene B-box sequence did not compete with each other for binding to TFIIIC2 any better than did an unrelated DNA sequence, indicating that TFIIIC2 interacts with 5S rRNA genes and tRNA-type genes through separate DNA-binding domains or polypeptides. PMID- 2601703 TI - Sequences upstream of AAUAAA influence poly(A) site selection in a complex transcription unit. AB - The adenovirus major late transcription unit (MLTU) encodes five colinear mRNA families, L1 through L5, each distinguished by a unique poly(A) site. Site selection is regulated during the course of infection, predominating early at the L1 site and late at the L2 through L5 sites. Two general mechanisms can be invoked to explain predominant usage of the L1 site early in infection. MLTU site selection may proceed in a first-come, first-serve manner whereby the L1 site is used most frequently because it is closest to the promoter. Alternatively, specific sequences flanking the L1 site may control predominant L1 site usage in a position-independent manner. To distinguish between these mechanisms, we constructed deletions in the L1 flanking sequences and inserted the mutated sites into either simple transcription units or mini-MLTUs encoding two poly(A) sites. The pattern of site selection for each construct was then quantitated by S1 nuclease analysis after transfection into 293 cells. The results indicated that L1 sequences upstream of AAUAAA define a novel selector element that can cause predominant L1 site usage at either position of a tandem transcription unit. The element did not significantly affect the stability or nucleocytoplasmic transport of L1 transcripts and was not required for efficient 3'-end processing in simple transcription units. Predominant L1 site usage required physical linkage of the processing signals and was independent of the major late promoter. PMID- 2601704 TI - Serum-inducible expression of transfected human c-myc genes. AB - Activation of the c-myc proto-oncogene is implicated in the initiation or progression of many vertebrate cancers. In nontransformed cells, the expression of c-myc is induced by growth factors. Studies have indicated that such induction is effected by multiple mechanisms. To study regulation of c-myc expression, a transfection system has been developed in which introduced c-myc genes exhibit serum-responsive activity. The responsiveness assayed is not mediated by increased transcription initiation. Rather, it is effected at a point(s) between transcription and stabilization of the RNA. PMID- 2601705 TI - Transcription factor E2F is required for efficient expression of the hamster dihydrofolate reductase gene in vitro and in vivo. AB - The dihydrofolate reductase (DHFR) gene encodes an enzyme important for metabolism and cell growth. We have found multiple DNA-protein interactions within the hamster DHFR gene promoter in vitro. These interactions occur over the consensus binding sites for two eucaryotic transcription factors. Sp1 and E2F. The DHFR E2F consensus site possesses a dyad symmetry and is unique in its location immediately 3' to the major transcription start site. The interaction of E2F with the DHFR promoter has been detected in HeLa nuclear extracts, confirmed by using partially purified E2F, and characterized by both enzymatic and chemical assays of the DNA-protein interaction. A mutation of the E2F recognition sequence which abolishes E2F binding to the DHFR promoter results in a two- to fivefold decrease of in vitro transcriptional activity and a fivefold reduction of DHFR promoter activity in transient-expression assays. Thus, the interaction of E2F with the DHFR promoter is required for efficient expression of the DHFR gene. PMID- 2601706 TI - Transcription factor IIIA gene expression in Xenopus oocytes utilizes a transcription factor similar to the major late transcription factor. AB - Xenopus transcription factor IIIA (TFIIIA) gene expression is stringently regulated during development. The steady-state level of TFIIIA mRNA in a somatic cell is approximately 10(6) times less than in an immature oocyte. We have undertaken studies designed to identify differences in how the TFIIIA gene is transcribed in oocytes and somatic cells. In this regard, we have localized an upstream transcriptional control element in the TFIIIA promoter that stimulates transcription from the TFIIIA promoter approximately threefold in microinjected oocytes. The upstream element, in cis. does not stimulate transcription from the TFIIIA promoter in somatic cells. Thus, the element appears to be oocyte specific in the context of the TFIIIA promoter. However, both oocytes and somatic cells contain a protein (or a related protein) that binds the upstream element. We have termed this protein from oocytes the TFIIIA distal element factor. The sequence of the upstream element is similar to the sequence of the upstream element found in the adenovirus major late promoter that is a binding site for the major late transcription factor. By gel shift analysis, chemical footprinting, methylation intereference, and point mutation analysis, we demonstrate that the TFIIIA distal element factor and major late transcription factor have similar DNA-binding properties. PMID- 2601707 TI - A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes. AB - Exposure of skeletal myoblasts to growth factor-deficient medium results in transcriptional activation of muscle-specific genes, including the muscle creatine kinase gene (mck). Tissue specificity, developmental regulation, and high-level expression of mck are conferred primarily by a muscle-specific enhancer located between base pairs (bp) -1350 and -1048 relative to the transcription initiation site (E. A. Sternberg, G. Spizz, W. M. Perry, D. Vizard, T. Weil, and E. N. Olson, Mol. Cell. Biol. 8:2896-2909, 1988). To begin to define the regulatory mechanisms that mediate the selective activation of the mck enhancer in differentiating muscle cells, we have further delimited the boundaries of this enhancer and analyzed its interactions with nuclear factors from a variety of myogenic and nonmyogenic cell types. Deletion mutagenesis showed that the region between 1,204 and 1,095 bp upstream of mck functions as a weak muscle-specific enhancer that is dependent on an adjacent enhancer element for strong activity. This adjacent activating element does not exhibit enhancer activity in single copy but acts as a strong enhancer when multimerized. Gel retardation assays combined with DNase I footprinting and diethyl pyrocarbonate interference showed that a nuclear factor from differentiated C2 myotubes and BC3H1 myocytes recognized a conserved A + T-rich sequence within the peripheral activating region. This myocyte-specific enhancer-binding factor, designated MEF 2, was undetectable in nuclear extracts from C2 or BC3H1 myoblasts or several nonmyogenic cell lines. MEF-2 was first detectable within 2 h after exposure of myoblasts to mitogen-deficient medium and increased in abundance for 24 to 48 h thereafter. The appearance of MEF-2 required ongoing protein synthesis and was prevented by fibroblast growth factor and type beta transforming growth factor, which block the induction of muscle-specific genes. A myoblast-specific factor that is down regulated within 4 h after removal of growth factors was also found to bind to the MEF-2 recognition site. A 10-bp sequence, which was shown by DNase I footprinting and diethyl pyrocarbonate interference to interact directly with MEF-2, was identified within the rat and human mck enhancers, the rat myosin light-chain (mlc)-1/3 enhancer, and the chicken cardiac mlc-2A promoter. Oligomers corresponding to the region of the mlc-1/3 enhancer, which encompasses this conserved sequence, bound MEF-2 and competed for its binding to the mck enhancer. These results thus provide evidence for a novel myocyte-specific enhancer-binding factor, MEF-2, that is expressed early in the differentiation program and is suppressed by specific polypeptide growth factors. The ability of MEF-2 to recognize conserved activating elements associated with multiple specific genes suggests that this factor may participate in the coordinate regulation of genes during myogenesis. PMID- 2601708 TI - Regulation of interaction of the iron-responsive element binding protein with iron-responsive RNA elements. AB - The 5' untranslated region of the ferritin heavy-chain mRNA contains a stem-loop structure called an iron-responsive element (IRE), that is solely responsible for the iron-mediated control of ferritin translation. A 90-kilodalton protein, called the IRE binding protein (IRE-BP), binds to the IRE and acts as a translational repressor. IREs also explain the iron-dependent control of the degradation of the mRNA encoding the transferrin receptor. Scatchard analysis reveals that the IRE-BP exists in two states, each of which is able to specifically interact with the IRE. The higher-affinity state has a Kd of 10 to 30 pM, and the lower affinity state has a Kd of 2 to 5 nM. The reversible oxidation or reduction of a sulfhydryl is critical to this switching, and the reduced form is of the higher affinity while the oxidized form is of lower affinity. The in vivo rate of ferritin synthesis is correlated with the abundance of the high-affinity form of the IRE-BP. In lysates of cells treated with iron chelators, which decrease ferritin biosynthesis, a four- to fivefold increase in the binding activity is seen and this increase is entirely caused by an increase in high-affinity binding sites. In desferrioxamine-treated cells, the high affinity form makes up about 50% of the total IRE-BP, whereas in hemin-treated cells, the high-affinity form makes up less than 1%. The total amount of IRE-BP in the cytosol of cells is the same regardless of the prior iron treatment of the cell. Furthermore, a mutated IRE is not able to interact with the IRE-BP in a high-affinity form but only at a single lower affinity Kd of 0.7 nM. Its interaction with the IRE-BP is insensitive to the sulfhydryl status of the protein. PMID- 2601709 TI - Context effects and inefficient initiation at non-AUG codons in eucaryotic cell free translation systems. AB - The context requirements for recognition of an initiator codon were evaluated in vitro by monitoring the relative use of two AUG codons that were strategically positioned to produce long (pre-chloramphenicol acetyl transferase [CAT]) and short versions of CAT protein. The yield of pre-CAT initiated from the 5' proximal AUG codon increased, and synthesis of CAT from the second AUG codon decreased, as sequences flanking the first AUG codon increasingly resembled the eucaryotic consensus sequence. Thus, under prescribed conditions, the fidelity of initiation in extracts from animal as well as plant cells closely mimics what has been observed in vivo. Unexpectedly, recognition of an AUG codon in a suboptimal context was higher when the adjacent downstream sequence was capable of assuming a hairpin structure than when the downstream region was unstructured. This finding adds a new, positive dimension to regulation by mRNA secondary structure, which has been recognized previously as a negative regulator of initiation. Translation of pre-CAT from an AUG codon in a weak context was not preferentially inhibited under conditions of mRNA competition. That result is consistent with the scanning model, which predicts that recognition of the AUG codon is a late event that occurs after the competition-sensitive binding of a 40S ribosome factor complex to the 5' end of mRNA. Initiation at non-AUG codons was evaluated in vitro and in vivo by introducing appropriate mutations in the CAT and preproinsulin genes. GUG was the most efficient of the six alternative initiator codons tested, but GUG in the optimal context for initiation functioned only 3 to 5% as efficiently as AUG. Initiation at non-AUG codons was artifactually enhanced in vitro at supraoptimal concentrations of magnesium. PMID- 2601710 TI - The Xenopus ribosomal DNA 60- and 81-base-pair repeats are position-dependent enhancers that function at the establishment of the preinitiation complex: analysis in vivo and in an enhancer-responsive in vitro system. AB - Although it is generally believed that the 60- and 81-base-pair (60/81-bp) repeats of the Xenopus laevis ribosomal DNA (rDNA) spacer are position independent transcriptional enhancers, this has not been shown directly. We have now developed a critical assay which proves that the 60/81-bp repeats do, in fact, stimulate transcription from promoters in cis and that they function in both orientations and when up to 1 kilobase pair from the initiation site. However, contrary to the widely accepted view, these elements are found to be highly position dependent, for they have no net effect when downstream of the initiation site within the transcribed region and they behave as transcriptional silencers of promoters in cis when moved greater than 2 kilobase pairs upstream of the initiation site. The 60/81-bp elements therefore are position-dependent 5' enhancers. We also found that this rDNA enhancer was polymerase I specific and that it was composed of duplicated, individually functional elements. Finally, we report an in vitro system that reproduces both cis enhancement and trans competition by the 60/81-bp repeats. Sequential-addition studies in this system demonstrated that the rDNA enhancer functions in trans at or before establishment of the stable transcription complex, not subsequently at each round of transcription. PMID- 2601712 TI - Circumstances and mechanisms of inhibition of translation by secondary structure in eucaryotic mRNAs. AB - This paper describes in vitro experiments with two types of intramolecular duplex structures that inhibit translation in cis by preventing the formation of an initiation complex or by causing the complex to be abortive. One stem-loop structure (delta G = -30 kcal/mol) prevented mRNA from engaging 40S subunits when the hairpin occurred 12 nucleotides (nt) from the cap but had no deleterious effect when it was repositioned 52 nt from the cap. This result confirms prior in vivo evidence that the 40S subunit-factor complex, once bound to mRNA, has considerable ability to penetrate secondary structure. Consequently, translation is most sensitive to secondary structure at the entry site for ribosomes, i.e., the 5' end of the mRNA. The second stem-loop structure (hp7; delta G = -61 kcal/mol, located 72 nt from the cap) was too stable to be unwound by 40S ribosomes, hp7 did not prevent a 40S ribosomal subunit from binding but caused the 40S subunit to stall on the 5' side of the hairpin, exactly as the scanning model predicts. Control experiments revealed that 80S elongating ribosomes could disrupt duplex structures, such as hp7, that were too stable to be penetrated by the scanning 40S ribosome-factor complex. A third type of base-paired structure shown to inhibit translation in vivo involves a long-range interaction between the 5' and 3' noncoding sequences. PMID- 2601711 TI - A nuclease-hypersensitive element of the human c-myc promoter interacts with a transcription initiation factor. AB - Transcription of the human c-myc oncogene is elaborately regulated, but the relevant molecular mechanisms are not yet understood. To begin to define elements and enzyme systems responsible for c-myc transcription in vitro, we partially purified a transcription factor essential for efficient and accurate in vitro initiation from the principal myc promoter, P2. DNA mobility shift assays located the factor binding domain at -142 to -115 with respect to the P1 promoter. This region contains pur/pyr sequences (predominantly purines in one strand), nuclease hypersensitive sites (U. Siebenlist, L. Henninghausen, J. Battey, and P. Leder, Cell 37:381-391, 1984; C. Boles and M. Hogan, Biochemistry 26:367-376, 1987), and a triple-helix-forming element (M. Cooney, G. Czernuszewicz, E. Postel, S. Flint, and M. Hogan, Science 241:456-459, 1988). Methylation interference mapping established that the factor, termed PuF, directly contacts the repeated palindromic sequence GGGTGGG of the -142/-115 element. The interaction of PuF with this cis-acting element is necessary for P2 transcription in vitro, for (i) deletion of this 5' region from the myc promoter greatly reduced transcription efficiency and (ii) a synthetic duplex oligonucleotide corresponding to the -142/ 115 sequence completely repressed c-myc transcription in the presence of the partially purified factor. These observations lend support to the hypothesis that pur/pyr sequences perform important biological roles in the regulation of c-myc gene expression, most likely by serving as transcription factor binding sites. PMID- 2601713 TI - Nuclear factor EF-1A binds to the adenovirus E1A core enhancer element and to other transcriptional control regions. AB - We have identified a cellular enhancer-binding protein, present in nuclear extracts prepared from human and rodent cells, that binds to the adenovirus E1A enhancer element I sequence. The factor has been termed EF-1A, for enhancer binding factor to the E1A core motif. EF-1A was found to bind to two adjacent, related sequence motifs in the E1A enhancer region (termed sites A and B). The binding of EF-1A to these adjacent sites, or to synthetic dimerized sites of either motif, was cooperative. The cooperative binding of EF-1A to these sites was not subject to strict spacing constraints. EF-1A also bound to related sequences upstream of the E1A enhancer region and in the polyomavirus and adenovirus E4 enhancer regions. The EF-1A-binding region in the E1A enhancer stimulated expression of a linked gene in human 293 cells when multimerized. Based on the contact sites for EF-1A binding determined by chemical interference assays, this protein appears to be distinct from any previously characterized nuclear binding protein. PMID- 2601715 TI - Antifolate drug selection results in duplication and rearrangement of chromosome 7 in Plasmodium chabaudi. AB - We selected lines of Plasmodium chabaudi that are resistant to high levels of the antifolate drug pyrimethamine and have shown that rearrangement and duplication of a portion of chromosome 7 has occurred in the resistant lines. This chromosomal duplication results in an increase in the chromosome number from 14 to 15: two derived chromosomes (450 kilobases and 1.1 megabases) were smaller than the original chromosome 7 (1.3 megabases), so that essentially only a 200 kilobase region was duplicated. This region contained the DHFR-TS gene and the closely linked Hsp70 gene. We have macrorestriction mapped chromosome 7 from the pyrimethamine-susceptible line (DS) and also the duplicated chromosome 7s in the resistant line. From these maps, we have proposed a process for the karyotype changes. Sequencing of the DHFR gene from the parent and derived chromosomes showed that there were no mutations in the coding sequence. As a result of the duplication of the DHFR-TS gene, there is at least a twofold increase in expression of the DHFR-TS gene, and this may explain the ability of the pyrimethamine-resistant lines to grow in increased amounts of the drug. PMID- 2601714 TI - Expression from the transferrin gene promoter in transgenic mice. AB - Transferrin is an iron-binding protein that is expressed as a major product in liver and secreted into the plasma. To study the tissue-specific regulatory regions of this gene, the genomic mouse transferrin (mTf) gene was cloned and characterized by partial sequence analysis and S1 nuclease mapping of the transcriptional start site. Fusion genes containing the transferrin gene promoter and 5'-flanking sequences were ligated to the human growth hormone (hGH) gene and used to produce transgenic mice. A deletion construct containing the -581 to +50 region of the transferrin gene was sufficient to direct a high level of liver specific expression resembling endogenous transferrin gene expression. Deletion to -139 base pairs of 5'-flanking sequence gave a construct which retained liver specificity, but the magnitude of expression decreased severalfold. These results demonstrate the presence of a liver-specific transcriptional element between -139 and +50 and suggest the presence of a distal element between -581 and -139 that can further increase expression. Surprisingly, fusion constructs containing -3 kilobase pairs (kb) of 5'-flanking sequence gave higher levels of mRNA in nonhepatic tissues than did either the -581 or -139 construct. Further studies indicated that the high levels of circulating hGH in these transgenic mice specifically induced the endogenous transferrin and albumin genes in liver and also stimulated the normally low levels of expression of the endogenous transferrin gene in brain, heart, kidney, and muscle. A mutated hGH gene that does not produce active growth hormone was fused to the -3- to +50-kb transferrin sequences to produce the -3-kb mTf-hGX construct. A liver-specific pattern of expression was observed in transgenic mice harboring the -3-kb mTf-hGX construct, and this mutated transgene was shown to be induced four- to sevenfold by either bovine or human growth hormone. These results demonstrate the presence of a growth hormone-responsive element between -3 and +50 kb in the 5'-flanking region of the mTf gene promoter. PMID- 2601716 TI - A liver-specific nuclear factor interacts with the promoter region of the large surface protein gene of human hepatitis B virus. AB - The outer envelope of the 42-nm virion of the human hepatitis B virus (HBV) is composed of the large, the middle, and the major surface proteins. Whereas the middle and the major surface proteins are transcribed from the SPII promoter of the pre-S/S gene, the large surface protein is transcribed from the SPI promoter located upstream of SPII. We have previously shown that transcription of SPI (comprising nucleotides [nt] -380 to +17) occurs preferentially in differentiated hepatoma cell lines (H.K. Chang and L.P. Ting, Virology 170:176-183, 1989). In this report, we further demonstrated that a sequence of 95 base pairs in the upstream region of SPI (nt -95 to +17) was necessary and sufficient for such preferential expression in differentiated hepatoma cells. By analysis of the expression of the chloramphenicol acetyltransferase gene in a series of mutants with deletions at the 5' end of SPI, we identified a positive transcriptional cis acting element mapping at nt -95 to -72 which appears to play a key role in the regulation of the expression of the large surface protein. This region shared a high degree of sequence homology with regulatory sequences of several liver specific genes from human, mouse, and rat, with a consensus sequence (G/A)GTTA(A/C)TNNT(C/T)NNC(A/C). We further identified a nuclear factor present in the nuclear extracts of differentiated human hepatoma cell lines which interacted specifically with this element of the SPI promoter. This nuclear factor was similar to the rat liver-specific factor HNF-1, since an oligonucleotide containing the recognition sequence of HNF-1 could efficiently compete for the human factor in a footprinting assay. The sequence at nt -93 to 68 which was bound by this factor in SPI was termed the HNF-1-binding element. Activation of the SPI promoter by human differentiated hepatocyte nuclear factor 1, described in this report, probably explains, first, the formation of the 42-nm virion specifically in liver but not in several other tissues despite the synthesis of the middle and the major surface proteins in those tissues, and second, why only differentiated hepatoma cell lines are able to produce 42-nm like virion particles on transfection by HBV DNA. PMID- 2601717 TI - Two chicken erythrocyte band 3 mRNAs are generated by alternative transcriptional initiation and differential RNA splicing. AB - The erythrocyte anion transport protein (band 3) mediates two distinct cellular functions: it provides plasma membrane attachment sites for the erythroid cytoskeletal network, and it also functions as the anion transporter between the erythrocyte cytoplasm and extracellular milieu. We previously showed that two chicken band 3 polypeptides are encoded by two different mRNAs with different translation initiation sites. Here we show that these two band 3 mRNAs are transcribed from two separate promoters within a single gene. In addition, the two pre-mRNAs are differentially spliced, leading to fusion with coding exons used in common in the two mRNAs. The chicken erythrocyte band 3 gene is therefore the first example of a gene that has two promoters within a single locus which function equally efficiently in one cell type at the same developmental stage. PMID- 2601718 TI - Spore coat genes SP60 and SP70 of Dictyostelium discoideum. AB - We cloned and sequenced the genes for two of the major proteins found in spore coats of Dictyostelium discoideum. The predicted translation product of each of these genes starts with a hydrophobic signal sequence that is subsequently cleaved. Expression of these spore coat genes is coordinate in prespore cells. PMID- 2601719 TI - The 5' noncoding region of the human leukemia-associated oncogene BCR/ABL is a potent inhibitor of in vitro translation. AB - The mRNA encoding the chimeric BCR/ABL oncogene, which is transcribed from the Philadelphia chromosome in human chronic myelogenous leukemia, has a 5' noncoding sequence greater than 500 bases in length which is highly GC rich and contains a short open reading frame. This untranslated sequence has a dramatic inhibitory effect upon translational efficiency in vitro. However, when BCR/ABL message is expressed in certain cell types such as the NIH 3T3 cell line, the 5' noncoding region has little inhibitory effect on translational efficiency. PMID- 2601720 TI - Transcriptional induction of the murine c-rel gene with serum and phorbol-12 myristate-13-acetate in fibroblasts. AB - Transcription of the c-rel proto-oncogene was induced transiently when resting mouse NIH 3T3 fibroblasts were stimulated with serum or phorbol-12-myristate-13 acetate. Addition of cycloheximide increased the steady-state levels of c-rel mRNA. These results indicate that c-rel is another member of the early-response gene family. PMID- 2601721 TI - trans activation of rat phosphoenolpyruvate carboxykinase (GTP) gene expression by micro-coinjection of rat liver mRNA in Xenopus laevis oocytes. AB - To study the liver-specific trans activation of the rat phosphoenolpyruvate carboxykinase (PEPCK) gene, the PEPCK promoter was linked to a reporter gene and was microinjected into Xenopus laevis oocytes alone or in conjunction with rat liver poly(A)+ RNA. The rat liver mRNA markedly enhanced the expression of the PEPCK-chimeric construct. This effect appeared to be sequence specific, as it was dependent on the presence of the intact promoter. Moreover, the RNA effect was limited to mRNA preparations from PEPCK-expressing tissues only. Finally, microinjection of size-fractionated liver mRNA revealed that the trans-acting factor(s) is encoded by RNA of 1,600 to 2,000 nucleotides, providing a direct bioassay for the gene(s) involved in this tissue-specific trans-activation process. PMID- 2601722 TI - RNA polymerase II transcription termination is mediated specifically by protein binding to a CCAAT box sequence. AB - A region in the adenovirus major late promoter (MLP) containing a CCAAT consensus sequence can direct transcription termination of RNA polymerase II, a mechanism that possibly prevents transcriptional interference from upstream genes. Using a chimeric plasmid template that contains the MLP directing expression of the simian virus 40 early region, we showed that an inserted oligonucleotide containing only 13 base pairs of MLP sequences, including the CCAAT box, is capable of inducing transcription termination in an orientation-dependent, position-independent manner. Point mutations within the CCAAT-specific protein binding site abolished this effect, while a base substitution outside of this region did not affect termination. These data suggest that termination is mediated by a CCAAT box-binding protein. Several other transcription factor binding sites do not, however, cause termination, suggesting that this may be a relatively specific property of a CCAAT-binding protein. PMID- 2601724 TI - Idiotypic cross-reactivity of anti-GAT and anti-alprenolol antibodies: an approach to the structural correlates of the pGAT idiotypic specificity. AB - Most anti-GAT antibodies in the BALB/c strain express a public idiotypic specificity (pGAT), which is encoded by specific germline genes (VH10, VK5.1 and VK1A5). One or both of these germline genes, referred to as "GAT-specific genes", are also used by four anti-alprenolol antibodies. Anti-Alp and anti-GAT antibodies show no cross-reactivity for the antigens. The light chain of one anti Alp antibody, 22C4, is encoded as the anti-GAT antibodies by a VK5.1-J2 combination and expresses part of the pGAT idiotopes, whereas the heavy chain is not "GAT"-related. Two anti-Alp using the VH10-VK5.1-J1 association do not express any of the pGAT idiotopes. Sequence comparison of the various CDR sequences points to the predominant role of the VH-CDR2 and VL-CDR3 for the constitution of the pGAT specificity. Regarding VL-CDR3, a drastic change in idiotypic determinants appears to be linked to V-J junctional diversity. PMID- 2601723 TI - Production and characterization of monoclonal antibodies specific for types 6 and 19 pneumococcal capsular polysaccharides. AB - The primary IgM and the secondary IgG antibody responses to pneumococcal capsular polysaccharides type 19 (S19) and type 6 (S6) coupled to sheep erythrocytes (S19 SRBC or S6-SRBC) differ in specificity. Although the primary IgM response appears to be totally specific for the pneumococcal cell wall carbohydrate (PnC) which is present in these polysaccharide preparations, the secondary IgG response appears to be completely specific for the immunizing capsular polysaccharide. A library of B cell hybridomas from fusions of splenocytes undergoing a primary response to an S19 preparation consisted entirely of PnC-specific hybrids. Thus, no evidence was obtained for the presence of capsular polysaccharide-specific IgM secreting B cells. IgM and IgG antibody secreting hybridomas were obtained, from fusions of splenocytes undergoing secondary S6- or S19-SRBC responses, to examine the antigen specificity of secondary antibody response of B cells at the clonal level. Many of the secondary IgM hybridomas secreted PnC-specific antibody; however, several S6-specific IgM secreting hybrids were also obtained, demonstrating a previously undetected population of B cells. All IgG secreting hybridomas obtained from S19- or S6-SRBC secondary response fusions secreted capsular polysaccharide-specific antibody, thus confirming the apparent absence of PnC-specific IgG secreting B cells in these responses. This method of immunization and challenge of mice with capsular polysaccharide coupled to erythrocytes, which results in the production of capsular polysaccharide-specific IgG responses, offers a relatively straightforward means to generate monoclonal antibodies specific for pneumococcal capsular polysaccharides. PMID- 2601725 TI - A serum protein SP40,40 modulates the formation of membrane attack complex of complement on erythrocytes. AB - SP40,40 was isolated from the soluble membrane attack complex (SC5b-9) by HPLC using a reverse-phase column. Amino acid compositions of its alpha- and beta subunits were similar to each other with the exception of glycine content. Amino terminal sequences of its alpha- and beta-subunits were identical to those of the subunits prepared from human serum, respectively, indicating that there was no degradation of SP40,40 during incorporation into SC5b-9. When guinea pig erythrocytes were incubated with C56f, C7, C8 and C9 in the presence of SP40,40, SP40,40 enhanced the hemolysis. The protein, however, inhibited the hemolysis when erythrocytes were pre-incubated with C56f and SP40,40 prior to the addition of C7, C8 and C9. These findings indicate that SP40,40 modulates the formation of membrane attack complex by interacting with C56f at the first step, and that the co-existence of other factors, besides C56f, is required for the enhancing activity of SP40,40. PMID- 2601726 TI - In vivo induction of A/J anti-ARS responses with different ranges of affinities: correlation between affinity and CRIA idiotype dominance. AB - The anti-ARS immune response of A/J mice is characterized by the reproducible and dominant selection of CRIA bearing antibodies. In this report, we have investigated the role of affinity for the antigen in the selection of antibody repertoire during an immune response. A/J anti-ARS responses with different ranges of affinities for arsonate were elicited by the injection of differently arsanylated carrier proteins. The selection of higher affinity A/J anti-ARS responses was shown to be associated with the induction of higher levels of CRIA bearing anti-ARS antibodies. A detailed idiotopic analysis also showed a more precocious selection of the CRIA "canonical combination" in the higher affinity anti-ARS responses. These results strongly suggest an important role for affinity and clonal selection in the dominant expression of the CRIA idiotype in the A/J anti-ARS response. PMID- 2601728 TI - Investigation of the relationships between plasma levels of ascorbate, vitamin E and beta-carotene and the frequency of sister-chromatid exchanges and release of reactive oxidants by blood leucocytes from cigarette smokers. AB - In this study the frequencies of sister-chromatid exchanges (SCEs) were correlated with measurements of the release of reactive oxidants by phagocytes, as determined by luminol-enhanced chemiluminescence (LECL), and levels of the anti-oxidants ascorbate, beta-carotene and vitamin E in blood specimens taken from 65 young asymptomatic cigarette smokers. Increased SCE frequencies correlated with LECL responses (p less than 0.0075) of activated blood phagocytes. Anti-oxidant levels did not correlate with either LECL or SCEs. These findings indicate that increased generation of reactive oxidants by circulating phagocytes from cigarette smokers are associated with cytogenetic changes. PMID- 2601727 TI - B cell activation by synthetic lipopeptide analogues of bacterial lipoprotein bypassing phosphatidylinositol metabolism and proteinkinase C translocation. AB - Synthetic analogues of bacterial lipoprotein induce proliferation of murine small resting B lymphocytes. We investigated the role of proteinkinase C (PKC) activation in lipopeptide-induced B cell stimulation. Using a standardized extraction procedure, there was no change in membrane bound and soluble PKC activity upon stimulation with lipopeptide. However, omitting Ca2+ chelators from the standard extraction medium resulted in a decrease of membrane bound PKC activity after stimulation. Lipopeptide failed to induce phosphoinositide degradation and the generation of the two second messengers cAMP and cGMP. To test whether guanosinetriphosphate-binding proteins are involved in lipopeptide induced signal transfer we investigated the effect of LiCl, choleratoxin and pertussistoxin on B lymphocyte proliferation. LiCl and pertussistoxin did not inhibit cell activation, whereas choleratoxin reduced the proliferation rate at concentrations higher than 0.5 micrograms/ml. Similar results were observed when LPS was used as mitogen, whereas the anti-immunoglobulin-induced B cell activation was inhibited by all three compounds. Our results show, that B cell activation by bacterial lipopeptides bypasses phosphatidylinositol metabolism and PKC translocation. PMID- 2601729 TI - Mutagenicity of ptaquiloside, the carcinogen in bracken, and its related illudane type sesquiterpenes. II. Chromosomal aberration tests with cultured mammalian cells. AB - The chromosomal aberration test using a Chinese hamster lung cell line (CHL) was carried out on ptaquiloside and its related compounds, hypoloside B, hypoloside C, illudin M and illudin S. Ptaquiloside induced chromosomal aberrations at doses as low as 4.5 micrograms/ml (0.0113 mM). The clastogenic effect was pH-dependent. The same activity was observed at a 90-fold higher dose at pH 5.3 in the culture medium compared with the activity at pH 7.4 or pH 8.0. Both hypoloside B and hypoloside C were also clastogenic at almost the same dose level as that of ptaquiloside. Illudin M and illudin S were also potent clastogens and induced aberrations at much lower doses than ptaquiloside. These results suggest that the clastogenic effect is involved in the mechanism of carcinogenic potency of ptaquiloside in animals. PMID- 2601730 TI - DNA-DNA dot hybridization technique used as DNA determination method in the alkaline elution analysis of DNA damage. AB - A DNA-DNA ('Southern') dot hybridization technique was adapted for use as a quantitative DNA detection method during alkaline elution analysis of irradiated rat cell material. In comparison to standard microfluorometric methods, similar gamma-ray dose-response relationships were obtained with less than 1% of the cell material when the dot hybridization assay was used. When a highly repetitive, long interspersed DNA element of the rat genome is used as a hybridization probe, as few as 10(4) cells of rat tissue or rat cell culture cells per sample with approx. 50 ng of DNA were sufficient to detect single-strand breaks and protein cross-links in the DNA of rat hepatocytes and cells of the nasal epithelium after in vitro gamma-irradiation. Since highly repetitive DNA elements are available from nearly all higher eukaryotes, this alternative approach of detecting DNA in alkaline elution analysis is generally proposed for tissues which yield only low amounts of cell material and/or which are difficult to label by radioactive DNA precursors. PMID- 2601731 TI - 'Petite' mutagenesis and mitotic crossing-over in yeast by DNA-targeted alkylating agents. AB - Although the biological properties (cytotoxicity, mutagenicity and carcinogenicity) of alkylating agents result from their bonding interactions with DNA, such compounds generally do not show any special binding affinity for DNA. A series of acridine-linked aniline mustards of widely-varying alkylator reactivity have been designed as DNA-directed alkylating agents. We have considered whether such DNA targeting has an effect on mutagenic properties by evaluating this series of drugs in comparison with their untargeted counterparts for toxic, recombinogenic and mutagenic properties in Saccharomyces cerevisiae strain D5. The simple untargeted aniline mustards are effective inducers of mitotic crossing over in this strain, but resemble other reported alkylators in being rather inefficient inducers of the "petite" or mitochondrial mutation in yeast. However, the majority of the DNA-targeted mustards were very efficient petite mutagens, while showing little evidence of mitotic crossing-over or other nuclear events. The 100% conversion of cells into petites and the lack of a differential between growing and non-growing cells are similar to the effects of the well characterised mitochondrial mutagen ethidium bromide. These data suggest very different modes of action between the DNA-targeted alkylators and their non targeted counterparts. PMID- 2601732 TI - In vivo micronucleus test using mouse hepatocytes. AB - The bone-marrow micronucleus (BMM) test is highly specific for clastogenic effects but its sensitivity is determined to a great extent by the substances tested, particularly by their metabolism. Some compounds, such as unstable mutagens or those which generate short-lived metabolites, are not detected in this test because the metabolites produced in the liver do not reach the bone marrow. In an attempt to provide qualitative and quantitative assessments of chromosomal mutations produced in vivo by genotoxic agents not detected in the mouse BMM test, a mouse-liver micronucleus test, adapted from Tates model, was developed. The animals were treated twice, with an interval of 24 h between treatments, and then subjected to partial hepatectomy (PH) 24 h after the second treatment in order to induce mitotic stimulation. The incidence of micronucleated hepatocytes was determined 96 h after PH. The test was evaluated with 5 procarcinogens, each with a complex metabolic pattern: dimethylnitrosamine (DMN), diethylnitrosamine (DEN), 1,1-dimethylhydrazine (1,1-DMH), 4-aminophenol (4 APOL), 4-aminobiphenyl (4-ABPYL) and one direct unstable mutagen, beta propiolactone (BPL). All these compounds are negative in the mouse BMM test but caused a major increase in the incidence of micronuclei in mouse hepatocytes. This test is simple and can be readily compared with the BMM test. Furthermore, it offers a better assessment of the impact of a compound at the chromosomal level in a metabolically competent cell and can therefore be used for the evaluation of the genotoxic activity of compounds with complex metabolic pathways. PMID- 2601733 TI - Japan still seeking a role. PMID- 2601734 TI - Fossils. Oldest reptile to leave UK? PMID- 2601736 TI - Medical Research Council. Increase softens blows. PMID- 2601735 TI - AIDS. Crisis ... what crisis? PMID- 2601737 TI - DNA structure. The turn of the quadruplex? PMID- 2601738 TI - Cleaning up after Chernobyl. PMID- 2601739 TI - A mutant protein kinase C that can transform fibroblasts. AB - Expression of normal protein kinase C (PKC) isoenzymes in fibroblasts has been shown to alter growth regulation but has failed to induce complete transformation of the recipient cells. Here we report on a murine ultraviolet-induced fibrosarcoma cell line which has an unusual PKC subcellular distribution with 87% of the PKC activity associated with the membrane. We have cloned and sequenced the alpha-PKC complementary DNA from ultraviolet-induced-fibrosarcoma cells and from mouse Balb/c brain and found four point mutations in the fibrosarcoma PKC, of which three are in the highly conserved regulatory domain and one is in the conserved region of the catalytic domain. Expression of this mutant alpha-PKC gene in normal Balb/c 3T3 fibroblasts results in a fibrosarcoma-like PKC membrane localization and in cell transformation, as judged by their formation of dense foci, anchorage-independent growth and ability to induce solid tumours when inoculated into nude mice. By contast, transfectants expressing the normal alpha PKC cDNA do not display a morphology typical of malignant transformed cells and fail to induce tumours in vivo. These findings demonstrate that point mutations in the primary structure of PKC modulate enzyme function and are responsible for inducing oncogenicity. PMID- 2601740 TI - Sound-induced motility of isolated cochlear outer hair cells is frequency specific. AB - The inner ear is capable of highly selective frequency discrimination. This is achieved not only by the travelling wave of the basilar membrane in the cochlear partition, but also by the active participation of nonlinear and vulnerable elements that enhance frequency selectivity. It has been shown that isolated mammalian outer hair cells respond with a change in length when subjected to sound stimulation at a fixed frequency. Here we investigate the motile behaviour of isolated cells when the stimulus frequency is varied between 200 and 10,000 Hz. By varying the frequency and the intensity of the tone, it is possible to obtain 'tuning curves' for the motile response. We demonstrate that the cell body of solitary hair cells, free from contact with the basilar membrane, shows a sharply tuned motile behaviour. We suggest that frequency selectivity in the organ of Corti is amplified by the tuned motility of the cell body of outer hair cells. PMID- 2601741 TI - Telomeric DNA dimerizes by formation of guanine tetrads between hairpin loops. AB - The telomeric ends of eukaryotic chromosomes are composed of simple repeating sequences in which one DNA strand contains short tracts of guanine residues alternating with short tracts of A/T-rich sequences. The guanine-rich strand is always oriented in a 5'-3' direction towards the end of the chromosome and is extended to produce a 3' overhang of about two repeating units in species where the telomeric terminus is known. This overhang has been implicated in the formation of several unusual intra-and intermolecular DNA structures, although none of these structures has been characterized fully. We now report that oligonucleotides encoding Tetrahymena telomeres dimerize to form stable complexes in solution. This salt-dependent dimerization is mediated entirely by the 3' terminal telomeric overhang (TT-GGGGTTGGGG) and produces complexes in which the N7 position of every guanine in the overhangs is chemically inaccessible. We therefore propose that telomeric DNA dimerizes by hydrogen bonding between two intramolecular hairpin loops, to form antiparallel quadruplexes containing cyclic guanine base tetrads. These novel hairpin dimers may be important in telomere association and recombination and could also provide a general mechanism for pairing two double helices in other recombinational processes. PMID- 2601742 TI - Sport psychology at the XXIVth Olympiad: prologue to the future? PMID- 2601743 TI - The practice of sport psychology. The physician as an informed resource. PMID- 2601744 TI - Malignant hyperthermia following isoflurane anesthesia in an American Lumbee Indian. PMID- 2601745 TI - Bulk laxative causing esophageal obstruction. PMID- 2601746 TI - A lifetime of sun. PMID- 2601748 TI - The value of health maintenance examinations in women. PMID- 2601747 TI - Tips for sun protection. PMID- 2601749 TI - Kinder, gentler "corrective action". Easing physician fears while simultaneously improving effectiveness of "peer review". PMID- 2601750 TI - He came, he Shaw, he conquered--pyrethrin insecticide exposure. PMID- 2601751 TI - Comments on ethical guidelines editorial. PMID- 2601752 TI - On a medical student's essay. PMID- 2601753 TI - [Limits to medical ability]. PMID- 2601754 TI - [The obstinacy of a profession]. PMID- 2601755 TI - [A family study of the initial Dutch patients with porphyria]. AB - The families of three porphyric patients originally described by Prof. Dr. A.A. Hijmans van den Bergh in the 1920s and of one porphyric patient described by Prof. Dr. I. Snapper in 1920 were traced and investigated to determine the type of the hereditary porphyria in each family. It was possible to confirm that Hijmans van den Bergh and coworkers had described hereditary coproporphyria and variegate porphyria. These were the first descriptions of these types of porphyria. The patient described by Snapper had acute intermittent porphyria. PMID- 2601757 TI - [The neglected blood pressure determination in pregnancy]. PMID- 2601756 TI - [Circumcision in women and infibulation]. AB - We saw three women born in the Horn of Africa in whom the residual state of infibulation could be observed. Female circumcision is applied to millions of women, particularly in Africa. The social significance, the origins and the medical and psychosexual implications are discussed. In order to improve women's health and status, the international health organisations can use their influence to replace mutilating excision and infibulation by a minor ritual incision. PMID- 2601758 TI - [ Lyme borreliosis, the 'Hocus Pas' among infectious diseases]. PMID- 2601759 TI - [Pain in the arm with tingling index and middle fingers, or the too-little-known prolapsed disk in the neck]. PMID- 2601760 TI - [Dynamic properties of the reflex to muscle stretching]. AB - The stretch and unloading reflexes were studied on extensor muscles of the hindlimb of decerebrated cats. It had been shown that nonlinear properties of the muscle dynamics were transformed under the reflex control and hysteresis inherent in the muscle itself was not removed by the stretch reflex. Hysteresis of the stretch reflex led to uncertainty of the equilibrium value of the muscle length and the equilibrium length depended on the movement prehistory. Stiffness of the muscle lengthening was shown to depend on the point of change in the movement direction. The observed nonlinearity of the stretch reflex was discussed from the functional point of view. PMID- 2601761 TI - [Participation of the calcium-binding membrane components in the neurophysiologic mechanisms of habituation in the edible snail]. AB - The native dynamics of Ca2+ binding with the membrane components in functionally different neurons of Helix pomatia when producing habituation to tactile stimuli are studied by fluorescent chlortetracyclin method. In the command neurons of the defensive behavior the weakening of the electrophysiological response characteristic for habituation and a decrease in the Ca2+ content were found. An increase in the Ca2+ content was found in supposed sensory neuron and in motoneurons in case of tactile stimulation, but according to electrophysiological criteria the habituation development in these cells was impeded. It is supposed that production of habituation is followed by hydrophobic-hydrophilic translocations of Ca2+-binding molecules in nerve cells. PMID- 2601762 TI - [The interaction of neurons characterized by a tonic reaction to sound with other neurons in the cat auditory cortex]. AB - Interaction of neurons with tonic response to sound with adjacent or distant (approximately 400-500 micrograms) cortex neurons was studied in acute experiments on 15 immobilized cats using a method of the cross-correlation analysis. A presence of synchronizing excitatory input common for the cells has been revealed in 26 pairs (72%) on the cross-correlograms. The results of the cross-correlation analysis in five pairs of neurons show mono- or polysynaptic excitatory effect of a tonic neuron to impulse activity of another neuron. Negative correlation indicative of the inhibitory influence of tonic neurons on impulse responses of other neurons of the same or adjacent auditory cortex column is revealed in five pairs of neurons, but the inhibitory influences may be considered as monosynaptic ones only in 3 pairs of these neurons (latency of interaction 1.0-1.5 ms). The data obtained permit concluding that the group of neurons characterized by tonic response to sound is a heterogeneous one in the functional respect. An assumption that some neurons of the tonic type are inhibitory interneurons of the auditory cortex, other excitatory ones is under discussion. PMID- 2601763 TI - [The action of dopamine and serotonin on the cells of an isolated spinal cord ganglion of the rat]. AB - The effect of bath application of dopamine (DA) and serotonin (HT) was studied in the isolated perfused dorsal root ganglia (DRG) of 30-36 days old rats by means of intracellular technique. 92% of investigated cells responded to the application of DA and 87%--to HT. DA and HT evoked depolarization in most of cells (64.6 and 73.7% of cells, respectively). Responses were dose-dependent and reversible. Depolarization caused by the DA and HT application was accompanied by a decrease in the input resistance (Rm) and alteration of the action potential shape. Hyperpolarization was followed by an increase of Rm. It was demonstrated that both DA and HT influenced predominantly DRG neurons with membrane biophysical characteristics inherent in small cells. Possibility of modulation of the afferent impulsation on the level of the primary sensory neurons is supposed. PMID- 2601764 TI - [The distribution of orientation-selective neurons in the thalamic nuclei and striopallidal complex of the human brain]. AB - The impulse activity of 177 neuronal populations analyzed in different nuclei of the thalamus and striopallidal complex during visual testing for orientation sensitivity in 9 parkinsonian patients, diagnosed and treated with the long-term intracerebral electrodes. Orientation-selective neurons related to visual perception constancy were revealed in centrum medianum, zona incerta and nucleus reticularis of the thalamus, nucleus caudatus, globus pallidus medialis. The comparative percentage and distribution of neurons with different properties in the thalamus and striopallidal nuclei were studied. PMID- 2601765 TI - [Changes in the synaptic apparatus of the associative area (field 5b) of the cat cerebral cortex following destruction of the lateral posterior thalamic nucleus]. AB - Quantity of normal and degenerating axonal terminals (AT) in area 5b of the associative cortex of cat was studied 2, 4 and 30 days after the electrolytic lesion of the thalamic nucleus lateralis posterior (LP). It was established that the quantity of degenerating AT in area 5b two and four days after the LP lesion was 7.4 and 7.2%, respectively. Four days after LP lesions the quantity of normal AT diminished by 16.4%, which was a direct result of excitatory AT degeneration. 40% of vanished AT formed synapses on dendrites and 60%--on spines. The quantity of axosomatic synapses in area 5b did not change after the LP lesion. Consequently, neurons in area 5b receive direct excitatory, predominantly axospinal input from LP. 30 days after LP lesions the total number of AT in area 5b was lower by 100% as compared with the control. Results and peculiarities of reinnervation in area 5b after degeneration of thalamocortical synapses are discussed. PMID- 2601766 TI - [The metabolic pathways of concanavalin A action on the chemosensitivity of the neuronal membrane]. AB - It has been shown that concanavaline A (Co A) inhibited those acetylcholine (ACh) and gamma-aminobutyric acid (GABA) responses of the membrane of dialyzed snail neurons which were blocked by ouabain. The inhibitory effect of Co A on these responses was removed at 5 degrees C. Co A had no significant influence on ACh responses which were insensitive to ouabain. Co A inhibited ACh-induced 86Rb+ ions efflux from the neurons preliminarily enriched by these ions. Co A has exerted a stimulating effect on the phosphorylation of neuronal membrane fractions. In this case Co A decreased the intracellular cyclic adenozine monophosphate (cAMP) content and increased the intracellular content of cyclic guanozine monophosphate. It is supposed that cAMP-independent membrane phosphorylation underlies the Co A inhibiting effect on the neuronal membrane sensitivity to ACh and GABA. PMID- 2601767 TI - [The neurons that determine the passive defense reaction in the pteropod mollusk Clione limacina]. AB - Pd13 neurons have been identified in pedal ganglia. They are always excited with a short latency following tactile stimulation of the head. Then the passive defensive reaction is arisen. Activation of neuron Pd13 induces inhibition of the whole locomotor generator. A number of neurons (P1 2, 3, 4 and 5) excited only after strong tactile stimulation have been identified in pleural ganglia. Activation of a certain pleural neuron induces inhibition of the whole locomotor generator. Inhibitory pleural neurons have synaptic contact with Pd13 neurons. Each spike in the pleural neuron is followed by one EPSP in Pd13 neuron. These relations are able to potentiation, soon changed by habituation. So, after strong tactile stimulation of the head, excitation of pleural neurons increases the activity of Pd13 neuron. Cerucal and ergotamine block the inhibition effect from Pd13 and pleural neurons on motoneurons, which testifies to the dopaminergic nature. PMID- 2601768 TI - [Serotonin modulation of the muscarinic cholinoreceptor status of the neurons in the mollusk Planorbarius corneus]. AB - It was found that serotonin relaxed desensitization and decreased acetylcholine induced potassium current. Effects of serotonin were connected with serotonin activated adenylate cyclase, adenosine 3':5'-cyclic monophosphate (cAMP) and phosphorylation of muscarinic receptor proteins by cAMP-dependent protein kinase. PMID- 2601769 TI - [The mechanism of action of pachycarpine on the nicotinic cholinoreceptors of sympathetic ganglion neurons in the rat]. AB - The mechanism of the pachycarpine action was studied in isolated superior cervical ganglion of rat using the patch-clamp method in the whole-cell recording mode. Action of the pachycarpine is not potential-dependent in the membrane potential range from +30 to -50 mV, the blockade increases during hyperpolarization of the membrane (-50-90 mV). Changes in the "dose-effect" dependence show that the blocking of nicotinic acetylcholine receptors is competitive both within the potential-dependent interval and within the potential independent one. PMID- 2601770 TI - [The effect of stimulation of the substantia nigra on low- and high-threshold startle reflexes in the cat]. AB - Effects of the substantia nigra (pars compacta) stimulation on two functional types of startle reflexes were studied in chloralose-anesthetized cats. The reflexes were the low-threshold ones evoked by tactile stimuli (T-reflex) and high-threshold ones evoked by intense peripheral nerve stimulation (spino-bulbo spinal, SBS reflex). It was found that substantia nigra stimulation exerted mainly inhibitory influences on both types of reflexes. However the depression of the SBS-reflex was always more profound and long lasting (up to 8 min) than that of T-reflex. The latter reflex was sometimes facilitated. PMID- 2601771 TI - [Calcium release from the intracellular stores of the soma of the mollusk neuron under the action of inositol triphosphate and its nonhydrolyzable analog GTP]. AB - The effects of intracellularly injected inositol trisphosphate (IP3) and nonhydrolyzed GTP analogue (Gpp[NH]p) on intracellular concentration of calcium ions [Ca2+]in was determined by fluorescence signals obtained from Helix pomatia neurons. At the same time these neurons were studied under the current clamp conditions. The IP3 and Gpp[NH]p injection caused a long-lasting [Ca2+]in increase in all neurons. Removal of the Ca2+ ions from external solution did not change the [Ca2+]in values. It is suggested that there is IP3- and GTP-dependent release of Ca2+ from intraneuronal stores in the Helix pomatia neurons. PMID- 2601772 TI - [A commentary on the article by V. P. Nikitin and M. O. Samoilov. The participation of the calcium-binding membrane components in the neurophysiologic mechanisms of habituation in the edible snail]. PMID- 2601773 TI - [Hearing adaptation in response to sonic and ultrasonic stimulation]. PMID- 2601774 TI - [Methodologic aspects of representing the functional reserves in the body adaptation of the athlete]. PMID- 2601776 TI - [The cytoarchitectonic characteristics of the cochlear complex in pinnipeds]. PMID- 2601775 TI - [The importance of peroxidation processes in aquatic and semiaquatic animals]. PMID- 2601777 TI - [Heterochronic maturation of the central and peripheral sections of the auditory system in cetaceans]. PMID- 2601778 TI - [Organizational characteristics of the superior olive complex and the lateral lemniscus in toothed whales]. PMID- 2601779 TI - [Characteristics of the motor activity of the contractile elements of the excretory apparatus of the mammary gland]. PMID- 2601781 TI - [The functional adaptation of the mammalian auditory system]. PMID- 2601780 TI - [The adaptive significance of peroxidation processes in mammary gland tissue]. PMID- 2601782 TI - [The regulatory role of factors in the reticuloendothelial system]. PMID- 2601783 TI - [Acoustic signaling in the common long-eared bat Plecotus auritus]. PMID- 2601784 TI - [Functional characteristics of hearing and the acoustic signaling system in hedgehogs of the fam. Erinaceus]. PMID- 2601785 TI - [Electrographic displays in analyzing sound signals of the frog against a background of the adapting action of noises]. PMID- 2601786 TI - [Neuronal reactions of the amygdaloid complex in bats to acoustic stimuli]. PMID- 2601787 TI - [The effect of the intensity of sound stimuli on the frequency and spatial characteristics of hearing in the porpoise]. PMID- 2601788 TI - [Neurophysiologic mechanisms of binaural hearing in the porpoise]. PMID- 2601789 TI - Thromboembolic complications in an asplenic HbE-beta-thalassaemia patient. AB - A patient, double heterozygous for HbE-beta-thalassaemia, had recurrent thromboembolic complications following splenectomy. In addition to marginally decreased protein C and S plasma levels, laboratory studies revealed a persistent thrombocytosis and markedly elevated plasma concentrations of platelet factor 4 (PF4). PF4 neutralizes the heparin anticoagulant activity. The increased PF4 levels explained the initial heparin resistance observed during anticoagulant treatment in this patient. Subsequent heparin loading tests revealed an abnormal reaction of the PF4 plasma levels, i.e. no increase of PF4. However, upon repeated heparin injections this PF4 response normalized, which may be due to depletion of the endothelial cell associated heparin mobilizable PF4 pool. These observations may be of relevance for the treatment of similar patients. PMID- 2601790 TI - Standard induction and low dose ara-C treatment in patients over 60 with AML or MDS. AB - In this retrospective study, 61 induction treatment periods in 57 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) were evaluated. According to the WHO performance status, 6 patients received no chemotherapy, 20 had low dose cytosine arabinoside (LD ara-C) induction courses, and 35 received standard induction consisting of daunorubicin and cytosine arabinoside. Untreated patients had a poor survival. Of the 20 patients with LD ara-C induction courses, 4 (20%) achieved complete remission (CR). Three patients (15%) died during induction. Of 35 patients with standard induction, 21 patients (60%) achieved CR. Toxicity was considerable - 11 patients (31%) dying during treatment. We conclude that patients over 60 yr of age with RAEB, RAEB-t or AML had a CR rate and survival comparable to those of younger patients if treated with standard induction chemotherapy at the cost of serious therapy-related complications. In patients who were judged not to be able to tolerate standard induction and who were subsequently treated with LD ara-C, complications occurred less frequently, but the CR rate was low and survival short. PMID- 2601791 TI - Renal handling of indomethacin: isolated membrane vesicles of proximal tubular cells as an in vitro model system for transport. AB - The indomethacin-transport properties of luminal and contraluminal membrane vesicles derived from dog renal proximal tubular cells were studied. In both membranes saturable sodium gradient-dependent transport of indomethacin, sensitive to probenecid, was observed. In luminal membrane vesicles uptake occurred predominantly by passive facilitated diffusion, whereas in contraluminal membrane vesicles, uptake was based upon both passive simple diffusion and active concentrative transport. As a result, indomethacin may accumulate in vivo in the tubular cells thereby exerting a direct nephrotoxic effect. PMID- 2601792 TI - Bacteraemia caused by Stomatococcus mucilaginosus in a granulocytopenic patient with acute lymphocytic leukaemia. AB - A patient undergoing chemotherapy for acute lymphoblastic leukaemia developed bacteraemia caused by Stomatococcus mucilaginosus while he was granulocytopenic. The organism may have been selected from the upper respiratory tract flora during prophylaxis with oral ciprofloxacin and then translocated to the blood stream via the mucosa. The strain produced an API-Staph profile indistinguishable from that of Micrococcus kristinae. Since a catalase-negative reaction is highly suggestive of S. mucilaginosus, the test should be performed routinely if this organism is not to be overlooked. PMID- 2601793 TI - Anaphylaxis as a rare complication of a barium enema examination. AB - A patient is described who developed anaphylaxis with respiratory and circulatory arrest after a single contrast barium enema examination. Since barium sulphate is an inert substance, the reaction must have been caused by additives present in the barium suspension. PMID- 2601794 TI - Can atherosclerotic complications be prevented? PMID- 2601795 TI - Fat patterning during weight reduction: a multimode investigation. AB - Changes in body composition during weight reduction of 20 obese women were quantified by anthropometry (weight, waist and hip circumferences, skinfold thicknesses determined with a skinfold caliper and ultrasonically), densitometry (hydrostatic weighing), tetrapolar bioelectrical impedance (TBI) and computed tomography (CT scan of abdomen and thorax). The average reduction in mean weight (92.7 kg), induced by an energy restricted diet over a period of 12 wk was 5.6 kg (5.8%). Fat areas were calculated from the CT scans of the thorax; intra abdominal fat and subcutaneous fat were separately calculated from the abdominal CT scans. Anthropometric and CT fat values were found to decrease significantly during weight reduction, whereas the percentages of body fat as determined by densitometry and TBI did not. The relative deposition of intra-abdominal and subcutaneous fat of 19 women did not essentially change after weight reduction. One woman, who had a relatively large intra-abdominal fat accumulation, lost more subcutaneous fat than intra-abdominal fat. It is concluded that in general fat patterning does not change during weight reduction. PMID- 2601796 TI - Pseudohallucinations in diabetic eye disease: a natural Rorschach test? AB - In diabetic eye disease, worsening vision may lead to the phenomenon of pseudohallucinations. Illustrated by a case history, a hypothesis is proposed which views this phenomenon as a kind of deprivation. This deprivation has implications for treatment, since reassurance and explanation seem more appropriate than pharmacological action. Other forms of sensory deprivation may occur in which one might expect the same situation, for example in polyneuropathy or impending deafness. PMID- 2601797 TI - Use of Permcath (Quinton) catheter in uraemic patients in whom the creation of conventional vascular access for haemodialysis is difficult. AB - During the last 4 years, the Permcath Quinton double-lumen silicone catheter was inserted into the internal jugular vein of 57 uraemic patients with difficulty for creating conventional vascular access for haemodialysis. In 4 patients, with definitive contraindication of conventional vascular access, this catheter still permits haemodialysis after a duration of 8-25 months. In 25 further patients with terminal uraemia, but poor vein system, it allowed the maturation of an arteriovenous fistula after 2-14 months of use. In 17 patients already on chronic haemodialysis, but who lost abruptly their vascular access (15 grafts and 2 arteriovenous fistulae), it allowed a new arteriovenous fistula to mature in 16 cases after a mean duration of 7.3 +/- months. In 5 patients with short life expectancy because of neoplasia, it allowed to dialyse them until their death which occurred after 6.5 +/- 2.2 months. In 6 patients with acute renal failure and haemostasis problems, it allowed to perform not only dialysis, but also plasmapheresis in 3 and parenteral nutrition in 3 other cases. The complications were the following: sepsis (n = 3); episodes of hypocoagulability due to inadvertent injection of heparin stored in the lumen (n = 2), thrombosis of the lumen (n = 3), and insufficient flow (n = 6). In no case these complications prevented continuation of haemodialysis. The catheter had to be removed in 2 cases because of septis and in 1 case because of insufficient flow. In 3 cases the catheter had to be replaced because of thrombosis and in 1 case because of laceration. These complication rates are, however, fewer than those reported in the literature for arteriovenous shunts or rigid subclavian and femoral catheters. The Permcath catheter seems, therefore to be the method of choice for immediated vascular access in patients in whom the creation of conventional vascular access is difficult. PMID- 2601798 TI - Hyponatremia in patients with the acquired immunodeficiency syndrome. AB - Of 103 patients with the acquired immunodeficiency syndrome (AIDS) admitted for acute opportunistic infections, 36 had serum sodium less than or equal to 130 mEq/l (130 mmol/l). In 12 the hyponatremia was associated with volume depletion and corrected with saline replacement therapy. In 23 it was associated with the syndrome of inappropriate antidiuretic hormones secretion (SIADH). One patient had adrenal insufficiency and the serum sodium corrected after steroid replacement. We conclude that hyponatremia is a common electrolyte abnormality in AIDS patients suffering acutely from opportunistic infections and that SIADH and volume depletion are important contributing factors. PMID- 2601799 TI - Lipid abnormalities and peroxidation of erythrocytes in nephrotic syndrome. AB - Serum lipid abnormalities are a common feature of the nephrotic syndrome. It is suggested that this may influence the membrane lipid composition of red cells, which on the other hand may result in an abnormal sensitivity of red cells to lipid peroxidation. Therefore, lipids of plasma and red cell membranes from 7 patients with nephrotic syndrome and from 31 healthy control subjects were examined. In addition, the consequences for the hydrogen-peroxide-induced lipid peroxidation of red cells as an index for their capacity to compensate for oxidant stress was measured. All patients were anemic. Their red cells exhibited a significantly increased susceptibility to lipid peroxidation. Fatty acid analysis revealed a decreased proportion of linoleic acid in plasma and red cell membrane. The content of cholesterol in patients' red cell membranes was clearly diminished. It is shown that this abnormality was related to the enhanced sensitivity of their red cells for peroxidative stress. The present study shows that in addition to an impairment of red cells' antioxidant enzymes, abnormalities of the membrane lipid composition should be considered investigating the cause for an increased susceptibility to lipid peroxidation. PMID- 2601800 TI - Sequence of glomerular changes in experimental endotoxemia: a possible model of hemolytic uremic syndrome. AB - Glomerular morphological changes produced by 5-hour intravenous infusion of endotoxin (40 micrograms/kg/h) were studied in 57 rabbits. During endotoxin infusion all animals developed signs of endotoxemia, anemia, and transient leukopenia and thrombocytopenia. Acute renal failure also developed in all animals. By light microscopy a marked polymorphonuclear cell infiltration was the prominent finding within 1 h from the beginning of the infusion. At hour 5 fibrin deposits and thrombi were detected in most animals. The abnormalities were reversible. By electron microscopy endothelial damage was detected few minutes after the beginning of endotoxin infusion followed by leukocyte and platelet infiltration in glomerular capillaries. Fibrin appeared at hour 5 as free strands into the lumens or in large clumps along the luminal surface of endothelial layer. Occasionally, occlusive fibrin thrombi were seen. At hour 48 only mild endothelial damage was seen, associated with few polymorphonuclear cells in the glomerular capillary lumens. These results document the sequence of renal changes in the best available animal model of hemolytic uremic syndrome. Beside endothelial damage, leukocyte infiltration in glomerular capillaries is a prominent finding suggesting a role of inflammatory cells in the development of microvascular thrombosis. PMID- 2601801 TI - Biosynthesis of complement C4 messenger RNA in normal human kidney. AB - Complementary DNA (cDNA) probes were used to investigate the extrahepatic production of the major histocompatibility complex (MHC)-linked complement components C4, factor B and C2 in various normal human tissues. The presence of the corresponding messenger RNA (mRNA) was tested by Northern blot analysis. Complement C4 mRNA was found in liver, and with high intensity also in normal kidneys. In contrast, no C2 mRNA and only very low amounts of factor B mRNA could be detected in the kidney. Slot blot hybridization was performed to quantitate the amount of C4 mRNA, and the intensity of C4 mRNA hybridization in the kidney samples was about 25% compared with liver RNA. C4-specific transcripts were not present in isolated glomeruli but in the renal interstitium. Other human tissues, such as tonsil, spleen, thymus, brain, lung and peripheral mononuclear cells, contained no C4 mRNA. Low amounts of C4 mRNA were found in colon, thyroid gland, lymph node and breast carcinoma. The results obtained with lung, where C2 mRNA was found but no C4 mRNA, further indicate an independent, tissue-specific regulation of the class III gene expression. The results, showing that the complement C4 genes are transcribed very efficiently in normal human kidney, suggest a direct role of complement C4 in renal pathogenesis. PMID- 2601802 TI - Hyperuricemia and renal handling of urate in primary hyperparathyroidism. AB - Serum urate and the renal handling of urate were measured in 37 patients with primary hyperparathyroidism and in normal sex- and age-matched subjects. Serum urate was increased in the hyperparathyroid group compared to the control group (6.23 +/- 1.46 versus 4.64 +/- 1.24 mg/100 ml; p less than 0.005), whereas the fractional excretion of urate was decreased in hyperparathyroid patients compared to the controls (6.80 +/- 2.69 versus 8.73 +/- 3.47%; p less than 0.005). Twenty four of these hyperparathyroid patients were studied 6 months after surgical correction of their disease. Serum urate decreased after surgery (5.14 +/- 1.65 mg/100 ml) compared to the preoperative state (5.92 +/- 1.46 mg/100 ml) and was no longer different from the normal values. The possible mechanisms of hyperuricemia associated with the hyperparathyroid state are discussed. PMID- 2601803 TI - Cardiac output, renal blood flow and hepatic blood flow in rats with glycerol induced acute renal failure. AB - Cardiac output (CO), renal blood flow (RBF) and hepatic blood flow (HBF) were measured by the microsphere method before (control) and at 4 and 10 h after the induction of acute renal failure by intramuscular injection of glycerol in water drinking, long-term saline-drinking and long-term captopril (converting enzyme inhibitor)-drinking rats. At 4 h after glycerol injection, CO, RBF and HBF significantly decreased in all three groups. At 10 h after glycerol injection, CO, RBF and HBF recovered to 88% of the respective control levels in only the saline-drinking rats, whereas CO, RBF and HBF further decreased to 53, 38 and 58% of the control levels, respectively in the captopril-drinking rats. At this time, not only acute renal failure but also hepatic disorder developed in the water drinking and captopril-drinking rats as indicated by elevations of serum creatinine, urea nitrogen, alanine aminotransferase and other blood chemistry levels. The development of acute renal failure was not suppressed by captopril, but by long-term saline load. Thus, we conclude that the decrease in CO is an important variable of the early decrease in renal and hepatic perfusion in glycerol-induced acute renal failure, and that the early recovery of HBF as well as RBF may play an important role in preventing the development of acute renal failure. PMID- 2601804 TI - Characteristics of rat kidney dopamine receptors and the effects of renal denervation and dopamine infusion on these receptors. AB - The characteristics of dopamine receptors, as well as the effects of denervation and dopamine infusion on dopamine receptors were studied using the radiolabeled receptor assay of [3H]-spiperone on rat kidney membrane preparations. The rat renal cortex was found to have a single class of [3H]-spiperone binding sites with a dissociation constant (Kd) of 13.5 +/- 2.2 nM. However, neither sulpiride nor serotonin strongly interacted with [3H]-spiperone binding, suggesting that DA1 receptors were predominant in the rat renal cortex. Denervation was performed by surgically stripping the nerves from the renal artery and coating them with 10% phenol. Chronic denervation had no significant effect on the affinity or maximum binding capacity of the renal dopamine receptors, although diuresis and the disappearance of catecholamine fluorophores in the denervated rats were observed. Chronic infusion of dopamine was performed using an osmotic minipump, resulting in a decrease in the number of rat kidney dopamine receptors. These results suggest that the dopamine receptor subtype in the renal cortex was mainly DA1, and that the major source of dopamine which affected the dopamine receptors in the rat kidney was not the nerve ending, but rather the circulation. PMID- 2601806 TI - Urinary elastase: the contribution of the lower urinary tract. PMID- 2601805 TI - Multiple myeloma and AL amyloidosis in a renal transplant recipient. AB - Seven years after a cadaver kidney transplantation a 33-year-old man presented with a monoclonal gammopathy secondarily complicated by AL amyloidosis mainly expressed as a sicca syndrome, gammopathy that ultimately developed into multiple myeloma. The mechanisms responsible for the occurrence of monoclonal gammopathy in renal transplant recipients are discussed. PMID- 2601807 TI - Plasma zinc decreases in hemodialysis patients treated with calcium carbonate as the phosphate binder. PMID- 2601808 TI - Acute effect of dipyridamole on urinary prostaglandin excretion. PMID- 2601809 TI - Vitamin E in plasma of patients with chronic renal insufficiency. PMID- 2601810 TI - Continuous ambulatory peritoneal dialysis does not prevent the development of dialysis-associated amyloidosis. PMID- 2601811 TI - Evidence of some nonglomerular bleeding in IgA nephropathy. PMID- 2601812 TI - International neurosurgery: neurosurgical training and practice in India, Korea, Japan, and Australasia. AB - During the 1985 annual meeting of the Congress of Neurological Surgeons in Honolulu, neurosurgical training and practice in India, Korea, Japan, and Australasia were discussed at the International Committee symposium. This article summarizes the information presented. India has about 300 neurosurgeons for a population of 650 million, while Japan has about 4,000 neurosurgeons and trainees for a population of 120 million. Korea has 424 neurosurgeons for a population of 41.5 million, and Australasia has 92 neurosurgeons and 19 trainees for 17.5 million people. Various other demographic, institutional, organizational, and economic aspects of neurological health care and delivery, education, and quality control are described. While financing and availability of adequate neurosurgical care remains a major problem in India, it appears that reducing the number of neurosurgical trainees remains, as it is in North America, a major issue in Japan and, to a lesser extent, in Korea. This problem, as well as certification of the quality of training, is being managed effectively in Australasia. PMID- 2601813 TI - Lipomeningioma. PMID- 2601814 TI - Outcome after operative treatment of intramedullary spinal cord tumors in adults: intermediate and long-term results in 51 patients. AB - The reported results of treatment of intramedullary spinal cord tumors (IMSCT) are difficult to interpret because of heterogeneous management strategies, small numbers of patients, and short periods of follow-up. In 1985 we published the early results of operative treatment of 29 patients with IMSCT and were cautiously optimistic that aggressive operative management would have a salutary effect on long-term outcome. In this report, the most recent clinical status of these 29 original patients is reviewed along with that of 22 additional ones, to assess the intermediate and long-term results of treatment of IMSCT in 51 patients who underwent microsurgical resection between 1981 and 1987. Of these 51 patients, 24 had ependymomas, 18 had astrocytomas, and the remainder had a variety of less common lesions. Thirty-seven patients survive and have been followed for periods up to 72 months (mean 38 months). The neurological conditions of 21 patients are improved or have stabilized following operation. The conditions of 16 patients are worse postoperatively: 11 from operation and 5 from progression of disease. Eight patients are neurologically intact, 7 walk independently but abnormally, 9 ambulate with the aid of a cane or walker, and the remaining 13 are not ambulatory. Twelve of 18 patients with astrocytomas and 2 of 24 patients with ependymomas have died after a mean survival of 10 months from operation. Patients with ependymomas who had gross total resection have fared the best, with no deaths or recurrences, but no relationship could be discerned between the extent of resection and outcome in patients with astrocytomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601815 TI - Long-term results of the surgical treatment of spinal dermoid and epidermoid tumors. AB - The clinical findings and the results of surgical treatment in 16 patients with spinal dermoid or epidermoid tumors are reported. In 9 patients the tumor capsule adhered so tightly to the nervous tissue that part of it was left in situ. In a follow-up study ranging from 5 to 30 years with a mean of 14.2 years only 1 patient had a recurrence of the tumor and 10 patients resumed a normal working life. PMID- 2601816 TI - Anterior cervical fusion and osteosynthetic stabilization according to Caspar: a prospective study of 41 patients with fractures and/or dislocations of the cervical spine. AB - Between June 1984 and April 1988, 41 patients with severe posttraumatic lesions of the cervical spine between the C2-C3 and the C7-T1 level seen consecutively were treated by an anterior cervical fusion and osteosynthetic stabilization according to Caspar. These patients were prospectively studied. Seven patients had a bilateral facet dislocation, 5 a unilateral facet dislocation, 9 an anterior subluxation, 9 an anterior compression fracture, 5 a hangman's fracture, and 6 a hyperextension injury at a lower cervical level. From a neurological point of view, there were 12 patients with an initial complete transverse lesion and 14 with an incomplete transverse lesion, and the remaining 15 patients did not have any deficit initially. Four patients died during the first 3 months after the operation. In 38 patients good anatomical position was obtained, generally by the intraoperative use of the vertebral distractor of Caspar. In all patients excellent immediate postoperative stability of the spine was obtained, although in 2 patients a second operation was necessary a few days after the first one. Postoperatively all patients were "immobilized" by a soft collar for 3 months. Four patients with an initial complete transverse lesion showed some neurological recovery in the postoperative period, and all patients with an incomplete transverse lesion improved. There were no postoperative neurological disturbances in the group of patients who were neurologically normal from the beginning. The mean postoperative hospitalization time was 13.6 days. These results were compared to the results from the literature, concerning other conservative and operative treatments for posttraumatic lesions of the cervical spine. PMID- 2601817 TI - Synchronous vertebral decompression and posterior stabilization in the treatment of spinal malignancy. AB - Thirty-four patients with metastatic tumors of the spinal column exhibiting vertebral collapse and posterior element disease were treated by a single-stage operation combining decompression of the vertebral body with posterior spinal instrumentation. Attention is drawn to the use of computed tomographic scanning in planning the operative approach. The indications for surgery were neurological deficit in 32 patients and pain in 2; 14 patients received preoperative radiotherapy. Of the 21 patients who were nonambulant preoperatively, 67% walked again, 21% regained sphincter control, and 68% had less pain. The surgical mortality was 12%; wound infection and dehiscence occurred in 15%. These results indicate that a single-stage decompression and posterior stabilization may improve neurological function dramatically in patients with malignant cord compression. The operative morbidity and mortality is comparable to that of laminectomy. PMID- 2601818 TI - Sacral and presacral tumors: problems in diagnosis and management. AB - We reviewed 9 cases of sacral tumors with presacral extension. These included 2 chordomas, 1 metastatic renal cell carcinoma, 2 schwannomas (1 malignant, 1 benign), 1 neurofibroma, 1 neurofibrosarcoma, 1 aneurysmal bone cyst, and an exceedingly rare meningioma. The sex of the patients was not significant. The age of the patients at diagnosis ranged from 13 to 68 years (mean, 47 years). Initial symptoms of low back and radiating leg pain were present in all but 1 patient. The duration of symptoms prior to diagnosis ranged from 1 month to 9 years (mean, 2.6 years). A delay in diagnosis of 2 years or more occurred in 6 of the 9 patients. Progressive perineal numbness and/or sphincter dysfunction were seen in 6 patients, and a palpable rectal mass was noted in 6 of 9 patients. The efficacy of various diagnostic tests is presented, as are the surgical options--needle biopsy and anterior and posterior approaches. Despite improved radiographic imaging techniques, these unusual tumors are often diagnosed at an advanced stage, and may masquerade as discogenic radiculopathy. Late diagnosis contributes to the difficulty of surgical extirpation. Anterior and posterior surgical approaches involving general, orthopedic, and urological surgeons may be required. PMID- 2601819 TI - Localized release of perivascular heparin inhibits intimal proliferation after endothelial injury without systemic anticoagulation. AB - Segmental endothelial desquamation of the common carotid artery was produced in 30 rats using a balloon catheter technique which produces consistent proliferation of intimal smooth muscle cells from 5 to 20 days after injury. Immediately after endothelial injury, 15 animals were treated with periadventitial application of heparin contained in a continuous-release drug delivery system using the polymer polyvinyl alcohol (PVA) and PVA alone applied in a similar fashion to 15 control rats. Animals were killed at 5, 10 and 20 days, respectively, after surgery by intracardiac perfusion-fixation, and vessels were prepared for light microscopy, scanning electron microscopy, and immunohistochemistry with antibodies directed against actin. At all time periods, there was a significant reduction in intimal cross-sectional area in heparin/PVA treated vessels compared to control vessels. Scanning electron microscopy showed complete absence of endothelial cells from the luminal surface in both control and treated arteries at all time periods without evidence of significant platelet aggregation. Immunohistochemistry demonstrated the presence of immunoreactive actin in the proliferating myointimal cells. Femoral venous prothrombin time and partial thromboplastin time were unchanged in heparin/PVA-treated animals compared to controls at 1, 5, and 10 days. Continuous-release polymer drug delivery can be used to apply heparin selectively to the adventitial surface of vessels and effect changes in the vessel wall over periods of up to 3 weeks. By this means, smooth muscle proliferation and subsequent vessel narrowing after endothelial injury were inhibited without systemic anticoagulation. This technique may be applicable to both clinical and research applications related to the pathophysiology of arterial injury. PMID- 2601820 TI - The use of electroencephalography and brain protection during operation for basilar aneurysms. AB - Intraoperative monitoring with electroencephalography and the use of brain protection with steroids, phenytoin, mannitol, and pentobarbital or etomidate were evaluated in 15 patients undergoing operation for an aneurysm of the upper basilar artery. One patient harbored a basilar trunk aneurysm, 1 an aneurysm of the proximal posterior cerebral artery, 3 an aneurysm of the superior cerebellar artery, and 10 an aneurysm at the basilar tip. The size of the aneurysms varied between 5 and 30 mm. Subarachnoid hemorrhage was the symptom exhibited in 12, mass effect the symptom in 2, and 1 patient was asymptomatic but had an angiogram because of amaurosis. There were 9 patients with multiple aneurysms, 5 of whom had aneurysms of the bilateral anterior circulation. Four patients underwent operation early. In 2 patients, the basilar artery was the sole or main blood supply of the whole brain. All patients except the one with the basilar trunk aneurysm were operated on via a transsylvian approach. All patients received 500 to 800 mg of phenytoin and 10 to 20 mg of dexamethasone shortly before and during surgery, and mannitol (0.8 g/kg) 15 minutes before the induction of hypotension or temporary clipping. Three patients showed slowing of electrical activity over the right hemisphere as a result of retraction of the internal carotid artery; with repositioning of the retractor, this disappeared within 10 minutes. Electrocortical silence was induced in 8 patients; this was in anticipation of prolonged moderate hypotension in 2, short deep hypotension in 2, temporary clipping of major vessels--including the basilar artery--in 2, and a combination of deep hypotension combined with temporary clipping in 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601821 TI - Causes of morbidity and mortality from surgery of aneurysms of the distal basilar artery. AB - Despite modern neurosurgical technology and neuroanesthetic care, treatment of aneurysms of the distal basilar artery remains fraught with complications. Between 1982 and 1988, 126 patients with aneurysms of the distal basilar artery who had been treated by 2 surgeons were retrospectively analyzed to determine the causes of morbidity and mortality from this disease and its treatment. Ten patients (8%) died, and 14 patients (11%) suffered permanent neurological disability after treatment. The causes of failed management could be grouped into the following categories: 1) direct effects of hemorrhage; 2) errors in surgical timing; 3) conceptual errors; 4) technical errors; 5) morbidity from delayed cerebral ischemia; and 6) complications of hypertensive/hypervolemic therapy for symptomatic vasospasm; a small group of patients who died despite having received what we consider excellent management were grouped under a seventh category, "bad luck." Frequently, patients who did poorly suffered from multiple complications, each of which contributed to their overall morbidity. It is our hope that increased awareness of these potential pitfalls and the further evolution of intravascular technique in selected cases will, in time, improve the outlook for patients suffering from these dangerous lesions. PMID- 2601822 TI - The calmodulin antagonist trifluoperazine provides mild prophylactic protection against cerebral vasospasm after subarachnoid hemorrhage, but no therapeutic value. AB - In vitro studies of the canine basilar artery have demonstrated that calmodulin antagonism can effectively inhibit cerebral arterial smooth muscle contractility. The prophylactic and therapeutic effectiveness of a potent calmodulin antagonist, the phenothiazine compound trifluoperazine (TFP), was investigated in vivo over a wide range of doses in the well-documented "double-subarachnoid hemorrhage" canine model of cerebral vasospasm. The compound is perhaps more well-known under its trade name, Stelazine, as a classic antipsychotic drug. The drug demonstrated no therapeutic relief of preexisting chronic cerebral vasospasm at any time during 2 days of systemic administration at any practical dose. At doses far in excess of the normally accepted therapeutic range in humans, a prophylactic regimen reduced the severity of chronic cerebral vasospasm after subarachnoid hemorrhage by approximately 35% compared to untreated dogs. PMID- 2601823 TI - Causes of infections in penetrating head wounds in the Iran-Iraq War. AB - Factors seemingly influential in postoperative central nervous system infections were evaluated in 379 patients who sustained missile wounds to the head during the Iran-Iraq War. The mean wound age was 49 hours. The site of injury and presence of retained bone and/or shell fragments did not have a significant effect on infection rate. Thirty-three of 379 patients developed cerebrospinal fluid (CSF) fistulas of which 12 (36%) were associated with infection. The infection rate was 6 of 346 (1.7%) in the absence of CSF leaks. There was a statistically significant association between CSF fistula and infection. All 6 positive cultures in patients with CSF fistulas were gram-negative. Thirty-two patients died during the study, a mortality rate of 8.4%. The mortality rate from infection was 1.8%. Two hundred seventy-seven of 347 patients were followed for a mean of 22 +/- 17 months during which time 2 patients were readmitted with central nervous system infections, both due to CSF leakage. CSF fistulas were the main predisposing factor in postdebridement central nervous system infections in this study. PMID- 2601824 TI - Proliferation activity in pituitary adenomas: measurement by monoclonal antibody Ki-67. AB - The monoclonal antibody (MAb) Ki-67 detects a nuclear antigen expressed by proliferating cells during the entire cell cycle. In contrast to conventional histological techniques, the use of MAb Ki-67 on frozen sections or cytological smear preparations allows direct determination of the growth rate of tumors routinely. Sixty-two pituitary adenomas were investigated by use of the MAb Ki-67 in a two-step avidin-biotin-peroxidase complex technique. The proliferation activity ranged from 0.1 to 2.8%. There was no significant difference between the proliferation and hormonal state of the adenomas. Adenomas for which there was histological evidence of dural infiltration, however, showed a statistically significant higher proliferation activity (P less than 0.05) compared to noninvasive adenomas. PMID- 2601825 TI - Chordoma and chondrosarcoma of the cranial base: an 8-year experience. AB - Between 1980 and 1988, 8 patients with chordomas and 9 with low-grade chondrosarcomas involving the cranial base were treated. All the patients were investigated preoperatively and postoperatively with computed tomographic or magnetic resonance imaging scans, according to a standard protocol. The tumors and the involved bony structures were surgically removed in one or more operations using different operative approaches. Ten patients underwent postoperative radiation therapy, either at our institution or prior to their referral to us. Total removal was defined as the absence of identifiable tumor on magnetic resonance imaging or computed tomographic obtained 3 months postoperatively, and was accomplished in 9 patients. The ability to achieve total removal was greatly increased in patients with tumors that had not previously been operated on. We believe that these tumors must be treated by aggressive surgical resection when initially diagnosed, and this can be accomplished with low morbidity. The follow-up period in our patients was too short to allow us to determine whether such total removals can result in a cure or in long-term control of these formidable tumors. PMID- 2601826 TI - Pterional approach for surgical treatment of olfactory groove meningiomas. AB - We present our experience with the surgical treatment of olfactory groove meningiomas using a pterional approach. This approach provides the advantages of previous techniques, such as preserving the frontal brain and superior sagittal sinus, early devascularization of the tumor, and late dissection of tumor borders. Moreover, it also compensates for the shortcomings of other techniques, e.g., compression of frontal bridging veins, late dissection of dorsal tumor aspects involving vessels and optic nerves as well as facultative infection and cerebrospinal fluid fistula-related complications caused by opening of frontal sinuses. To date, 11 patients were treated in this way. As we encountered no surgical complications in our series we are encouraged to present our procedure. PMID- 2601827 TI - Schwannoma associated with anomalous division of the median nerve: case report. AB - The authors present a case of a schwannoma associated with high division of the median nerve in a patient who had previously had a diagnosis of a ganglion. The case is presented and the literature concerning these 2 conditions is reviewed. PMID- 2601828 TI - Mobile schwannoma of the cauda equina diagnosed by magnetic resonance imaging. AB - Three cases of a mobile cauda equina schwannoma, preoperatively diagnosed by magnetic resonance imaging, are described. When dealing with tumors of the cauda equina, it is important to carry out a second magnetic resonance imaging scan after changes in posture, bearing in mind the possibility of mobility of the tumor. PMID- 2601829 TI - Arterio-inferior sagittal sinus fistulae: case report. AB - The management of the case of a 9-year-old boy with progressive cognitive impairment due to arteriovenous fistulae at the apex of the inferior sagittal sinus is reported. This represents a unique location for an extraparenchymal deep central arteriovenous malformation. The patient underwent staged ablation of the lesion by surgery. The postoperative course was complicated by expansion of an aneurysmal vein of Galen undergoing thrombosis and hyperperfusion syndrome, but the patient ultimately made a satisfactory recovery. PMID- 2601830 TI - Fatal phenytoin-related toxic epidermal necrolysis: case report. AB - Toxic epidermal necrolysis is a rare but often fatal hypersensitivity reaction to numerous agents, including most anticonvulsants. The authors present a case of fatal phenytoin-related toxic epidermal necrolysis in a patient who was given prophylactic anticonvulsant therapy after he sustained a moderately severe closed head injury. The typical course and current management of toxic epidermal necrolysis are reviewed, as are the indications for the prophylaxis of posttraumatic epilepsy. PMID- 2601831 TI - Traumatic trochlear nerve palsy diagnosed by magnetic resonance imaging: case report and review of the literature. AB - Although head trauma is the leading cause of acquired trochlear nerve dysfunction, it receives little attention in the neurosurgical literature. A case is reported of closed head injury that resulted in a right superior oblique palsy in association with incoordination on the left side. Diagnostic imaging revealed a normal cranial computed tomographic scan and a left dorsal midbrain lesion on magnetic resonance imaging scan. The relevant anatomy is reviewed, as well as the action of the superior oblique muscle, its agonists and antagonists, and the clinical manifestations of superior oblique dysfunction. This case is one of the few we are aware of in which a relatively isolated trochlear nerve palsy is the result of a lesion that can be documented by diagnostic imaging, and the first in which the imaging modality is magnetic resonance imaging scan. PMID- 2601832 TI - Balo's concentric sclerosis: a variant of multiple sclerosis associated with oligodendroglioma. AB - We report a case of Balo's concentric sclerosis, a rare and acute variant of multiple sclerosis, which coexisted with an oligodendroglioma. The demyelinating lesion was clinically silent and was detected at necropsy. The pathogenesis of concentric sclerosis and the relationship of the demyelinating lesion to the evolution of the glial neoplasm is briefly discussed. PMID- 2601833 TI - Laser-assisted microsurgical extirpation of a brain stem cavernoma: case report. AB - A 43-year-old woman presented with progressing signs of a space-occupying brain stem lesion. A computed tomographic scan revealed a hyperdense process located in the pons. Magnetic resonance imaging confirmed the lesion, which had a reticulated core of increased and decreased signal intensity. Vertebral angiography did not show any vascular supply of the process. The patient was operated upon in the lateral park bench position. The lesion, being located close to the exit zone of the trigeminal nerve, could be removed totally with incision of the brain stem and atraumatic vaporization of the tumor tissue with the CO2 laser. Despite the fact that the histopathological examination revealed a cavernous angioma the application of laser energy was judged to be extremely valuable for the surgical procedure. It was concluded that with proper selection of application mode and wattage the CO2 laser may be used for extirpation of vascularized lesions also especially when situated in or close to deep lying vital structures of the brain. PMID- 2601834 TI - Implantation of a reservoir for recurrent subdural hematoma drainage. AB - In a prospective study 144 adult patients with chronic subdural hematomas were randomly divided into three treatment groups after burr-hole evacuation. The two commonly used procedures (external closed system drainage and aspiration and irrigation without any drainage) were compared to a modified technique: permanent subdural drain with subcutaneous reservoir. After the hematoma was washed out with saline solution, a silicon catheter with multiple perforations was introduced into the subdural cavity and connected to a Rickham reservoir, fixed in the frontoparietal burr hole. In patients who showed secondary deterioration or enlargement of the residual hematoma as proven by computed tomographic scan, the reservoir was punctured and the subdural fluid aspirated. The great advantage of this method is that it is practicable at the bedside as well as in the outpatient department, thus making it possible to reduce the number of additional operations. The incidence of symptomatic residual or recurrent hematoma was similar in all three groups. The reoperation rate was 4-fold greater in the groups treated with conventional therapy, when compared to the group with the implanted system. At the same time there was no indication that the implantation of the drain was less safe, as judged by the incidence of seizures and infections. PMID- 2601835 TI - Percutaneous transfacial needle biopsy of a middle cranial fossa mass: case report and technical note. AB - A case of a patient with a middle fossa mass that was considered to be either a metastatic lesion or a benign intracranial neoplasm is presented. The definitive management of the patient depended on a tissue diagnosis. A biopsy was obtained using a transfacial needle aspiration technique through the foramen ovale. The details of this procedure are described. PMID- 2601836 TI - Cholinergic and noradrenergic denervations decrease labelled purine release from electrically stimulated rat cortical slices. AB - The origin of cortical purine release was investigated by measuring [3H]purine release from electrically stimulated cortical slices of rats after neurotoxic lesions of cholinergic, noradrenergic and serotoninergic pathways innervating the cortex. Purines were labelled by incubating the cortical slices with [3H]adenine. The 3H efflux at rest and during stimulation, analysed by high performance liquid chromatography, consisted of adenosine, inosine, hypoxanthine and a small amount of nucleotides. Twenty days after unilateral or bilateral lesion of the nucleus basalis a marked decrease in choline acetyltransferase activity was associated with a decrease in [3H]purine release. A linear relationship was found between the decrease in choline acetyltransferase activity and [3H]purine release. A partial recovery in both choline acetyltransferase activity and [3H]purine release was observed eight months after the lesion. Twenty days after intra cerebroventricular injection of 6-hydroxydopamine a 59% decrease in cortical noradrenaline content was associated with a 44% decrease in [3H]purine release. Conversely, no change in [3H]purine release was found in rats in which a 89% decrease in cortical serotonin content was induced by intra-cerebroventricular injection of 5,7-dihydroxytryptamine. The decrease in [3H]purine release after the lesion of the cholinergic and noradrenergic pathways may depend on metabolic changes, a loss of a stimulating influence of acetylcholine and noradrenaline or may indicate a release of [3H]purine from cholinergic and noradrenergic fibres. PMID- 2601837 TI - Neural basis of olfactory memory in the context of pregnancy block. AB - In mice, only strange male pheromones block pregnancy; pheromones of the familiar male with which the female has mated have the capacity to block pregnancy but are ineffective with the consort female. Hence, some form of recognition/memory to the stud male is formed at mating. By infusing lignocaine locally into the accessory olfactory bulb and second order olfactory synapses in the medial nucleus of the amygdala, this study localizes changes that occur in the accessory olfactory bulb at mating to be subsequently important in preventing the stud male's pheromones from blocking pregnancy. Further attention is focused on the dendrodendritic synapses between mitral and granule cells in the accessory olfactory bulb. Blockade of the GABA receptors (granule to mitral cell synapse) in the accessory bulb without mating, but in the presence of male pheromones, prevents any male from blocking pregnancy. Conversely inhibition of protein kinase C, a second messenger system activated by excitatory amino acids (mitral to granule cell synapse), in the accessory bulb during a 4-h period after mating permits all male pheromones including the stud's to activate pregnancy block. While blockade of protein kinase C activity during the critical exposure time for memory formation prevents memory formation, infusions of a protein synthesis inhibitor (anisomycin) are without effect. However, protein synthesis inhibition in the accessory olfactory bulb in the late phase of the critical exposure time (3-6 h after mating) does prevent memory formation. These studies show that changes in synaptic plasticity in the accessory olfactory bulb following mating are critical to recognition of the stud male's pheromones, hence preventing these from subsequently blocking pregnancy. PMID- 2601838 TI - Synaptic remodeling in the rat arcuate nucleus during the estrous cycle. AB - Adult female rats showing regular vaginal cycles were studied in order to determine the number of axosomatic synapses in thin sections of the arcuate nucleus. The number of synapses per length of perikaryal membrane was significantly decreased in estrus, compared to other days of the estrous cycle (P less than 0.05). The reduction in the number of synapses in estrus was accompanied by a decrease in the percentage of the average length of perikaryal membrane covered by presynaptic terminals and by an increase in the percentage of membrane in close apposition of glial processes. Since the average perikaryal perimeter was not significantly changed during the estrous cycle, these results indicate a net decrease in the number of arcuate nucleus axosomatic synapses between proestrus and estrus, with a reinnervation of arcuate neurons between estrus and metestrus. These results suggest that there is a physiological synaptic turnover in the arcuate nucleus of the rat during the estrous cycle. PMID- 2601839 TI - Long-lasting insomnia induced by preoptic neuron lesions and its transient reversal by muscimol injection into the posterior hypothalamus in the cat. AB - In order to analyse the role of the anterior hypothalamus in the regulation of the sleep-waking cycle we made bilateral neuronal lesions at different levels of the anterior hypothalamus in cats, by means of microinjections of a cell-specific neurotoxin:ibotenic acid. These lesions resulted in severe insomnia in eight cats. This insomnia was characterized by a large decrease or even disappearance of paradoxical sleep and deep slow wave sleep and, to a lesser extent, by a decrease of light slow wave sleep, for 2-3 weeks. In the other five animals, we observed a large reduction of deep slow wave sleep (0-40% of control level), but a less intensive decrease of time spent in paradoxical sleep (50-75% of control level) and no marked effect on light slow wave sleep. During the first 3-6 postoperative days we also noticed hyperthermia in all cats; thereafter, the animals presented only a slight increase in brain temperature which did not appear to trigger the sleep impairment. Histological analysis of the different lesions revealed that the insomnia could be attributed to neuronal cell body destruction in the mediobasal part of the anterior hypothalamus covering; the medial preoptic area and a narrow portion of the lateral preoptic area as well as a restricted part of the anterior hypothalamic nucleus. In order to investigate the putative role of the posterior hypothalamic structures in the mechanism of insomnia after lesion of the mediobasal preoptic area neurons we injected an agonist of GABA into the ventrolateral part of the posterior hypothalamus to locally depress the neuronal activity. The bilateral intracerebral microinjection of muscimol (0.5-5 micrograms) induced a transient intensive hypersomnia (slow wave sleep and paradoxical sleep). These findings indicate that neuronal cell loss in the mediobasal preoptic area induced a long lasting insomnia. Thus, it may be hypothesized that the integrity of this structure is necessary for sleep appearance. Finally, our data are in keeping with an intrahypothalamic regulation of the sleep-waking cycle. PMID- 2601840 TI - Choline acetyltransferase-like immunoreactivity in the hippocampal formation of control subjects and patients with Alzheimer's disease. AB - A qualitative and quantitative immunohistochemical study of cholinergic systems in the human hippocampal formation was performed with an antibody against choline acetyltransferase. Four control subjects and six patients with Alzheimer's disease, matched for age and post-mortem delay, were examined. Immunoreactive nerve fibres and terminals were visualized, but no cholinergic cell bodies were seen. The distribution of the fibres and terminals suggests that a major afferent cholinergic pathway enters the hippocampus dorsally via the fimbria-fornix, a minor input entering from the temporal lobe along the alvear path. The cholinergic innervation suffers some degenerative change in normal aged subjects, but decreases considerably in density in patients with Alzheimer's disease. The extent of the decrease differs somewhat among the subregions of the hippocampus, but is homogeneously distributed within each subregion, and throughout the rostrocaudal extent of the structure. Compensatory sprouting in reaction to denervation was not detected. PMID- 2601841 TI - Modular organization of ON and OFF responses in the cat lateral geniculate nucleus. AB - Multiunit mapping techniques were used to investigate whether or not units with ON- and OFF-center receptive fields occur in an orderly arrangement in the cat lateral geniculate nucleus. In the A layers, ON- and OFF-center sites were partially segregated in the dimension parallel to the laminae, with ON-center sites predominant at the dorsal surface of each layer and OFF-center sites relatively more numerous at the ventral surface of the layer. Microelectrode tracks were placed to traverse the visual field map in the nucleus parallel to projection lines, parallel to isoelevation lines and parallel to isoazimuth lines. The tracks placed parallel to projection lines contained long sequences of units of the same center sign, providing evidence that ON and OFF zones are organized in vertical modules which span much or all of the thickness of a layer. The tracks placed parallel to isoelevation and isoazimuth lines contained alternating clusters of ON- and OFF-center sites. These clusters were larger in the dimension representing isoelevation than in the dimension representing isoazimuth. Taken together, these results indicate that the cat lateral geniculate nucleus contains ON and OFF modules oriented perpendicular to the layers. PMID- 2601842 TI - Quantitative electrophysiological studies of regenerating visuotopic maps in goldfish--I. Early recovery of dimming sensitivity in tectum and torus longitudinalis. AB - Refinement and connectivity in the regenerating retinotectal system of goldfish were studied quantitatively by electrophysiological methods. One optic nerve was crushed intraorbitally in fish kept at 25 degrees C. At different postcrush times, visually-evoked multiunit activity was recorded from the superficial layers of tectum, and from the torus longitudinalis. Responses in torus longitudinalis were used as a test of retinotectal connectivity because torus longitudinalis derives a visuotopic map from a tectal projection. The stimulus, effective for both the early retinotectal projection and torus longitudinalis, was a 10 degrees wide vertical black stripe rotated horizontally at 25 degrees/s through both visual fields. Activity from repeated sweeps was averaged to yield receptive field profiles in the horizontal dimension. Normally, profiles from tectum were dual-peaked and 20 degrees wide at half maximum amplitude; torus longitudinalis profiles were bell-shaped and 41 degrees wide. Between 20 and 40 days postcrush, tectum gave broad low-amplitude (25% normal) profiles that were roughly visuotopic. Over the same period, torus longitudinalis gave profiles of relatively high amplitude (69% of normal) that were also broadened but normally visuotopic. The widths of both tectal and torus longitudinalis profiles declined with the same exponential timecourse, reaching normal values by 80-100 days. Torus longitudinalis profiles were on average 21.6 degrees wider than tectal profiles at all stages of regeneration. The results agree with previous anatomical observations showing that optic fibers initially form much enlarged arbors that shrink over time, and suggest that arbors engage in widespread synaptic connections, at least with tecto-torus longitudinalis cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601843 TI - Quantitative electrophysiological studies of regenerating visuotopic maps in goldfish--II. Delayed recovery of sensitivity to small light flashes. AB - The regenerating retinotectal projection of goldfish was mapped with punctate flashes of light produced by red light-emitting diodes. The characteristics of multiunit receptive fields were studied in fish kept at 25 degrees C at different times after unilateral optic nerve crush. From about 20 days, when the first visually-evoked responses to black-on-white stimuli appeared, until about 40 days, no consistent responses to light-emitting diodes could be obtained, although high-contrast, long-duration light-emitting diode stimuli elicited weak off-responding. At around 40 days, responses to light-emitting diodes reappeared as the amplitude of evoked multiunit activity increased sharply. At their emergence, light-emitting diode-sensitive multiunit receptive fields were irregular and only slightly enlarged, but quickly regained normal shape and size. Conformity to a linear and uniform visuotopography recovered more slowly and, in some individuals, incompletely. The results suggest that "on" and "off" optic fiber systems, probably with small terminal arbors, are functionally expressed at a later time in regeneration than the predominantly "off" system manifested earlier. The different time courses of recovery in these systems explain several aspects of the recovery of visual behavior during optic nerve regeneration. PMID- 2601844 TI - The alpha-bungarotoxin receptor purified from a human neuroblastoma cell line: biochemical and immunological characterization. AB - The pharmacological and electrophysiological characteristics of the alpha bungarotoxin receptor present on the human neuroblastoma cell line IMR-32 indicate that this receptor is not associated with an acetylcholine-operated ionic channel. In this paper we report its biochemical purification and immunological characterization. This molecule has a standard sedimentation coefficient of 10S and sodium dodecyl-sulphate gel electrophoresis shows that it is made up of three polypeptide chains of molecular weights of 67,000, 60,000 and 52,000. Ligand binding to blots of purified receptor revealed that only the polypeptide of molecular weight 52,000 is bound by [125I]alpha-bungarotoxin. The purified alpha-bungarotoxin receptor was bound by polyclonal antibodies raised against purified fetal calf, Torpedo and chick optic lobe nicotinic receptors and by the sera of myasthenic patients. Furthermore, despite the fact that a number of different immunological techniques were used, it was impossible to label this alpha-bungarotoxin receptor with mAb 35, a monoclonal antibody which binds some neuronal nicotinic receptors. Rabbit antisera against the purified alpha bungarotoxin receptor were used to compare this protein with other known nicotinic receptors and, once again, it was demonstrated that there is some immunological cross-reactivity between the alpha-bungarotoxin receptor present on neuroblastoma cells and Torpedo, fetal calf and chick optic lobe nicotinic receptors. All these immunological data, together with previously published pharmacological and molecular biology data, demonstrate that the alpha bungarotoxin receptor present in nerve cells is neither a muscular nor a neuronal nicotinic receptor, although it has similarities with both. PMID- 2601845 TI - Localization of striatal dopamine receptor function by central injection of an irreversible receptor antagonist. AB - The stereotypic head-down sniffing response to systemically administered apomorphine (0.65 mumol/kg) was assessed in rats 48 h after the bilateral injection of 0.2-0.5 microliters of the irreversible receptor antagonist N ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (60 micrograms/microliters) into the caudate-putamen and nucleus accumbens. This response was significantly attenuated in animals that had received injections of N-ethoxycarbonyl-2-ethoxy-1,2 dihydroquinoline into the anterior/ventral part of the caudate-putamen but not in those that received injections into regions more dorsal/posterior. Animals were killed after apomorphine challenge and the region of dopamine D1 or D2 receptor reduction due to N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline mapped and quantified. This analysis revealed that the dopamine receptors involved in the apomorphine-induced stereotyped head-down sniffing response were located in a discrete region of the ventrolateral caudate-putamen and the dorsolateral nucleus accumbens. Animals that were pretreated with the selective dopamine D2 receptor antagonist raclopride (0 20 mumol/kg, i.p.) 20 min prior to central injection of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline into this area showed a dose dependent protection of the stereotyped sniffing response to systemic apomorphine 48 h later. This combination of techniques constitutes a novel way to investigate striatal function and the results obtained support the concept of a functional subdivision of both the caudate-putamen and the nucleus accumbens. PMID- 2601846 TI - Magnetic mu rhythm in man. AB - We report detection of magnetic mu rhythm in four subjects using a large-area seven-channel first-order superconducting quantum interference device gradiometer. The polarity of this activity was opposite at the upper and lower ends of the rolandic fissure, and during the sharp transients the field patterns could be satisfactorily explained by a current dipole model. The equivalent dipoles were located close to the sources of the early somatosensory evoked field component N20m, which suggests that the mu rhythm is generated mainly at the primary somatosensory hand projection area. The frequency spectrum of the mu had major peaks around 10 and 21 Hz in all subjects. The high-frequency activity was blocked by clenching of the fist, but not by opening of the eyes, in agreement with characteristics of the electric mu rhythm. PMID- 2601847 TI - An autoradiographic analysis of neurogenesis in the chick retina in vitro and in vivo. AB - Patterns of [3H]thymidine incorporation during neurogenesis of the embryonic chick retina have been compared in vitro and in ovo. Pieces of posterior, undifferentiated retinas were dissected from embryos on day 6 of incubation (E6) and cultured in the presence of [3H]thymidine. Label was added to the medium for 3 h on day 1, 2, 3 or 4 in culture. The retinas were fixed on the fifth day, embedded in epon, sectioned and processed for autoradiography. In parallel experiments, in ovo injections were made on embryonic day 6, 7, 8 or 9 (E6-E9). On E12 the embryos were fixed and a piece of the posterior retina from each eye was dissected and processed for autoradiography as above. Results show that the retinal explants develop well in culture and all of the layers of the neural retina differentiate. However, the cultured retinas are thinner than those grown in ovo. [3H]Thymidine labeling indicates that nearly all retinal neurons undergo their final mitotic divisions between E6 and E9. In addition the patterns of labeling in culture are similar to those in ovo. Most neurons, including the majority of cells in the ganglion cell layer and outer nuclear layer, are labeled on the first three days in culture and in E6-E7 embryos, while labeled cells are restricted to the inner nuclear layer in older specimens. Counts of labeled and unlabeled neurons in the ganglion cell layer suggest that the temporal pattern of neurogenesis in culture lags behind that in the embryo by about one day but that the spatial patterns of cell migration are the same. PMID- 2601848 TI - Topographical assessment of accumulated radioactivity from [14C]2-deoxyglucose and [6(-14C)]glucose in rat forebrain at different survival periods. AB - The uptake and retention of radioactivity was measured in discrete areas of rat brain at different times after i.v. injection of [14C]2-deoxyglucose or [6( 14)C]glucose, in unrestrained rats. In most brain regions, the accumulation of radioactivity from the two compounds was similar when a 30-min survival period for [6(-14)C]glucose was compared to a 45-min survival period for [14C]2 deoxyglucose. However, at those times, autoradiographic images of the hippocampus and piriform cortex appeared distinctly different for [14C]2-deoxyglucose and [6( 14)C]glucose. Relatively more radioactivity accumulated from [14C]2-deoxyglucose, compared to [14C]glucose, in the stratum lacunosum-moleculare of the hippocampus and in layer 4 of the isocortex. In contrast, relatively more radioactivity accumulated from [6(-14)C]glucose, compared to [14C]2-deoxyglucose, in the molecular and granule cell layers of the dentate gyrus, the CA1 pyramidal cell layer of the hippocampus, and in layer 2 of the piriform cortex. When rats were killed 5 min after injection of [6(-14)C]glucose, the relative neuroanatomical distribution of radioactivity was similar to the 30-min survival period, except in layer 4 of the isocortex, where relatively more radioactivity was present at the early time. When rats were killed 5 min after injection of [14C]2 deoxyglucose, in 20 of 24 brain regions examined, the absolute and relative amounts of accumulated radioactivity were similar when compared to that of the 45 min survival period. In contrast, the absolute and relative amounts of radioactivity were significantly greater for the 5-min compared to the 45-min survival period, in the CA1 pyramidal cell field, dentate gyrus, and layer 2 of the piriform cortex. For those regions, the appearance of autoradiograms prepared from rats killed 5 min after administration of [14C]2-deoxyglucose is remarkably similar to the appearance of autoradiograms prepared from rats killed 5 or 30 min after injection of [6(-14)C]glucose. Possible mechanisms are discussed to explain the observed differences in the accumulation of radioactivity in discrete brain regions after injection of [6(-14)C]glucose and [14C]2-deoxyglucose at the different survival times examined. PMID- 2601849 TI - 'Clock' and 'motor' components in absolute coordination of rhythmic movements. AB - Human subjects swung, through motions at the two wrists, hand-held pendulums of variable mass and length. Within a pair, the two pendulums could be of the same or different magnitude. The subjects were required to produce a coordinated state in which the two rhythmic units oscillated at a single common period. Fifty-four conditions of absolute coordination, that is, 54 different pairs of wrist pendulum systems, were investigated for each of three subjects in the course of six sessions. Each condition of absolute coordination was conducted in the out of phase mode and at the single most comfortable period. The period variances of the right and left systems in the 162 instances of absolute coordination were analysed according to a method that assumes that a timekeeper function and a motor implementation function contribute independently to the variance in the periodic timing of a rhythmic movement. The major findings were that in absolute coordination: (a) a system's 'motor' variance, but not its 'clock' variance, depended on the deviation of the period of absolute coordination tau from the system's characteristic period; (b) right and left 'clock' variances were related and (c) neither the 'motor' variances nor the 'clock' variances were affected by deviations in the mean phase relation from 180 degrees. The results were discussed in terms of their implications for interpreting von Holst's notions of maintenance tendency and magnetic effect and, more generally, the neural and dynamical basis of absolute coordination. PMID- 2601850 TI - A theoretical analysis of extracellular punctate stimulation around dendrites. AB - The polarization of neuronal trees by external point stimulation is modelled. In one form of model, an almost spheroidal field encloses the dendritic tree. Radially projecting, electrically linear dendrites, along with extracellular medium, are considered to occupy the entire field. The spheroid is modified by a penetrating cone that can surround the stimulating microelectrode; here, and in the rest of the infinite volume outside the field, there is only extracellular medium. A second form of linear electrical model, representing sections of membrane and cytoplasm by means of lumped electrical components commonly known as compartments, is used to validate the field construct. A similar spatial distribution of induced steady-state membrane potential emerges from the two forms of model, for a given morphology and electrophysiology. Compartmental models are also used to demonstrate time-courses of membrane charging. At the soma, if the point source is nearby, charging proves to be essentially complete in less than one time-constant. The soma thresholds under steady-state polarization from different electrode distances are plotted for field models of various electrical space-constant, size and shape of spheroid, and eccentricity of the soma. Characteristic cathodal or anodal thresholds, depending on the particular cell parameters, are revealed for specific electrode trajectories. The range of threshold-distance relations obtained in previously published experiments match those given by the models, when the time-course of charging is taken into account. PMID- 2601851 TI - Location of a transiently expressed glycoprotein in developing cerebellum delineating its possible ontogenetic roles. AB - The development pattern of a 31,000 mol. wt phosphatidyl inositol-anchored membrane glycoprotein was followed during development in mouse and rat cerebellum using monoclonal antibody 194-653. The epitope was developmentally regulated and particularly abundant in post mitotic precursors of granule cells, newly formed parallel fibres and unmyelinated axons of the white matter between the 5th and the 15th postnatal days. It decreased considerably thereafter. In the adult, a significant although relatively low staining was observed only in white matter. Observation at the ultrastructural level showed that most of the 31,000 mol. wt glycoprotein was very concentrated on neuronal plasma membranes. A little immunoreactivity was also found intracellularly at the perinuclear membrane of neuroblasts of the external germinal layer. The antigen was present in the coated pits and intracellularly in coated vesicles. Immunochemical studies indicated that 31,000 mol. wt antigen was very likely to be a previously identified transient concanavalin A-binding glycoprotein insoluble in neutral detergents (Reeber et al., 1981; Brain Res. 229, 53-65). It appeared to be one of the glycoprotein ligands for two endogenous mannosyl-lectins isolated from rat cerebellum (Zanetta et al., 1985, Devl. Brain Res. 17, 233-243, Zanetta et al., 1987, J. Neurochem. 49, 1250-1257). The affinity of the 31,000 mol. wt glycoprotein for the two endogenous lectins, together with its developmental pattern and localization indicate that it could be an important molecule for contact guidance during migration of neurons and for myelination and could take part in other ontogenetic steps. PMID- 2601852 TI - Ontogeny of M1 and M2 muscarinic binding sites in the striatum of the cat: relationships to one another and to striatal compartmentalization. AB - The ontogeny of striatal M1 and M2 muscarinic cholinergic binding sites was studied autoradiographically in cats ranging in age from embryonic day 40 to postnatal day six. Direct labeling with [3H]pirenzepine revealed M1 sites, and M2 sites were labeled with [3H]N-methylscopolamine in the presence of pirenzepine. In serial tissue sections, distributions of striatal M1 and M2 sites were compared to one another and to patterns of acetylcholinesterase staining and tyrosine hydroxylase-like immunoreactivity. The younger fetal material demonstrated heterogeneous distributions for both subtypes of muscarinic binding sites, with patches of dense binding corresponding to islands of dopaminergic nigrostriatal innervation. For both M1 and M2 binding, lateral to medial and caudal to rostral density gradients were present in the patches and in the surrounding matrix. During fetal development and into the perinatal period, overall muscarinic binding increased, but more so in the matrix than in the patches. By postnatal day six striatal M2 binding appeared nearly homogeneous. M1 binding, however, was slightly more concentrated in patches than in matrix. The patches of elevated M1 binding were still present at maturity, and corresponded to striosomes. These findings suggest that the ontogenetic regulation of muscarinic binding sites is influenced by location relative to striatal compartments, and that expression of M1 and M2 binding site subtypes is differentially regulated. PMID- 2601853 TI - A direct catecholaminergic projection from the brainstem to the neurohypophysis of the rat. AB - The presence of the catecholamines dopamine and noradrenaline in the posterior pituitary is well documented. Dopaminergic terminals are thought to derive from cells in the periventricular hypothalamus including the rostral arcuate nucleus, but the origin of the noradrenergic terminals is uncertain. The majority of central noradrenaline-containing neurons are in the brainstem and lesions of the ventral noradrenergic tract significantly reduce the noradrenaline content of the neural lobe. We have explored the possibility of a direct noradrenergic projection from the brainstem to the neural lobe using as a retrograde tract tracer horseradish peroxidase alone or in combination with immunohistochemical detection of tyrosine hydroxylase. Horseradish peroxidase was injected into the neural lobes of 20 rats using a ventral approach, and the animals were perfusion fixed 12 h later. In all 20 cases, cells retrogradely labelled with horseradish peroxidase were found not only in the periventricular zone and magnocellular nuclei of the hypothalamus but also in the A2 region of the brainstem. In all six cases simultaneously processed for horseradish peroxidase and tyrosine hydroxylase immunohistochemistry, retrogradely labelled cells in both the arcuate nucleus and A2 region were found to be tyrosine hydroxylase-positive. These findings demonstrate the presence of a direct projection from catecholaminergic neurons in the A2 region of the brainstem to the neurohypophysis. Since catecholaminergic neurons in this region are known to be noradrenergic and lesions of the ventral noradrenergic tract deplete the neurohypophysis of noradrenaline, these neurons may represent an important source of noradrenaline in the neurohypophysis. PMID- 2601854 TI - Synaptic connections of GABA-containing boutons in the lateral cervical nucleus of the cat: an ultrastructural study employing pre- and post-embedding immunocytochemical methods. AB - The lateral cervical nucleus receives input from the spinocervical tract and projects to the thalamus and mesencephalon. The organization of this nucleus was examined using two immunocytochemical methods. Pre-embedding immunolabelling was performed using an antibody against glutamate decarboxylase, and post-embedding immunogold-reaction was performed with an antibody to glutaraldehyde-fixed GABA. Light microscopic analysis of material reacted for glutamate decarboxylase revealed that punctate structures were present throughout the nucleus and were associated with large cells in the dorsolateral region of the nucleus. Electron microscopy demonstrated that the punctate structures were synaptic boutons which formed symmetrical synaptic junctions with dendrites and somata of cells in the nucleus. The ultrastructural preservation of material prepared for the post embedding immunogold technique was superior to that prepared for pre-embedding immunostaining. Positively labelled synaptic boutons exhibited high colloidal gold density and, like those prepared for the pre-embedding method, formed symmetrical synaptic junctions with dendrites and somata of neurons. Labelled boutons were densely packed with irregularly-shaped synaptic vesicles. They displayed characteristics which were distinct from those unlabelled boutons. Boutons, revealed by both immunolabelling methods, were not observed to form synaptic associations with other axon terminals and were presynaptic to dendrites and somata only. Therefore, it is probable that such boutons are responsible for postsynaptic inhibition of cells in the nucleus. In view of this evidence, it is concluded that the lateral cervical nucleus is not simply a relay but is actively involved in processing sensory information. PMID- 2601855 TI - The effect of temperature on electrical interactions between antidromically stimulated frog motoneurons and dorsal root afferent axons. AB - The effect of temperature on electrical interactions between antidromically stimulated motoneurons and dorsal root afferents was studied in the isolated and hemisected spinal cord of the frog, superfused with Ringer in which Ca2+ was equimolarly replaced by Co2+ or Mn2+ to suppress chemical synaptic transmission. Suction electrodes were used for stimulating and/or recording from dorsal and ventral roots from segments IX or X. Intrafibre recordings from sensory fibres were made at their point of entry into the spinal cord. Supramaximal ventral root stimuli elicited two distinct responses in the segmental dorsal root. First a brief short-latency depolarizing potential. Second, at temperatures below 11 degrees C, a second depolarizing root potential appeared following the short latency depolarizing potential-I. Amplitude and duration of short-latency depolarizing potential-II reversibly increased as the bath temperature was decreased, reaching a maximum at 3 degrees C. Between 8 and 3 degrees C, short latency depolarizing potential-II increased in amplitude by 20%/degrees C. In contrast short-latency depolarizing potential-I did not show substantial changes with temperature. The short-latency depolarizing potential-II, unlike short latency depolarizing potential-I showed stepped fluctuations in amplitude, and appeared to be composed of unitary events. Intrafibre records revealed that the unitary events corresponded to action potentials on individual dorsal root fibres. Double shocks applied to the ventral root, at constant bath temperatures (below 11 degrees C), revealed facilitation of the short-latency depolarizing potential-II, which was maximal between 50 and 80 ms and lasted about 200 ms. Neither the antidromic motoneurone field potential nor the short-latency depolarizing potential-I were facilitated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2601856 TI - Acetylcholinesterase stain intensity variation in the rat dentate gyrus: a quantitative description based on digital image analysis. AB - Three-dimensional patterns of variation in the intensity of acetylcholinesterase histochemical staining and the width of stain-defined subregions were quantified for the dentate gyrus of the adult male Long-Evans rat. Matched tissue sections sampled through the central hippocampal formation of five rats were measured with a digital image analysis computer system. The width and stain intensity were determined for defined portions of the dentate gyrus related to gross acetylcholinesterase staining patterns and the known distribution of dentate afferents. Normalized values reflecting stain intensity at defined positions within this standardized sampling array were examined to investigate regional differences in acetylcholinesterase distribution along the primary dendritic axis of dentate granule neurons. The data illustrate quantitative differences in the partitioning of acetylcholinesterase as a function of intrahippocampal position. The variation is more pronounced in the septal-temporal axis than the granule cell layer crest-tip axis. Furthermore, the septal-temporal variations in acetylcholinesterase intensity demonstrate some independence according to proximal-distal location within the molecular layer. The results suggest that acetylcholinesterase distribution within the dentate gyrus may reflect local physiological characteristics of those afferent systems related to this enzyme, including but not necessarily limited to those that are specifically cholinergic. PMID- 2601858 TI - A system of corticotropin releasing factor-containing amacrine cells in the rat retina. AB - Immunohistochemical processing of Long-Evans retina wholemounts using an antiserum directed against rat, human corticotropin releasing factor revealed a group of immunoreactive amacrine cells. Two subpopulations could be distinguished based primarily on the location of their cell bodies. One subpopulation had cell bodies situated along the junction of the inner nuclear layer and the inner plexiform layer. The other subpopulation had cell bodies in the ganglion cell layer. The latter was judged to be displaced amacrine cells since double-label experiments indicated that the pattern of corticotropin releasing factor-like immunoreactive staining in the ganglion cell layer did not coincide with that of ganglion cells labeled retrogradely with fluorogold. Corticotropin releasing factor-like immunoreactive amacrine cells on either side of the inner plexiform layer emitted processes which ramified extensively in sublamina 5 and, to a lesser degree, in sublamina 4. A minority of these cells also sent a single process to ramify in sublamina 1. Throughout the retina, corticotropin releasing factor-like immunoreactive cells were distributed relatively evenly, with a tendency to peak in the superior temporal region. Despite the anatomical classification into two subpopulations, it is proposed that the corticotropin releasing factor-like immunoreactive cells are functionally one system, influencing preferentially synaptic interactions associated with the inner half of the inner plexiform layer. The results of this study provide anatomical basis for further investigations of corticotropin releasing factor as a putative peptidergic neurotransmitter in the retina. PMID- 2601857 TI - Effect of kainate-induced seizures on tissue trace element concentrations in the rat. AB - It has been shown that epileptics have lower mean blood concentration of manganese than do controls but the cause of this abnormality has not been determined. In order to investigate the effects of seizures on manganese distribution in the body, rats were treated with kainic acid to produce spontaneous seizures which were quantitated for number and severity. Manganese, zinc, copper and iron concentrations were determined in blood, brain, liver, heart and kidney. Kainate-treated animals ate more food but gained less weight than controls. Liver and kidney manganese concentrations were significantly higher in kainate-treated animals than in controls. Blood manganese concentration showed a significant negative correlation with seizure index while heart manganese concentration showed a significant positive correlation with seizure index. None of the other trace elements showed a significant correlation between trace element concentration and seizure index in any of the tissues, although iron concentration was lower in brain and copper concentration was lower in kidney of kainate-treated animals than in their appropriate controls. These data show that manganese concentrations are generally elevated in tissues of kainate treated animals. This increased manganese concentration may be related to the increased energy demand of these animals. PMID- 2601859 TI - Expression of the egg-laying hormone genes in peripheral neurons and exocrine cells in the reproductive tract of the mollusc Lymnaea stagnalis. AB - The neuroendocrine caudodorsal cells play an important role in the control of reproduction in Lymnaea stagnalis. These neurons produce at least nine neuropeptides which are encoded by caudodorsal cell hormone-I and -II genes. The role of some of these peptides in the control of reproduction has been established. The present study demonstrates that the transcription and translation of the caudodorsal cell hormone genes also proceeds abundantly in the reproductive tract of this hermaphroditic animal. In the female part of the reproductive tract neurons were found to express gene I. These neurons are most likely involved in the control of transport of the eggs and egg-masses and in the regulation of secretory activity from the female accessory sex glands. In the male part of the reproductive tract exocrine secretory cells express gene I or gene II. The gene products are secreted into the male duct and transferred to the female copulant during copulation. Furthermore, putative sensory neurons in the skin were found to express gene I. The results indicate that in L. stagnalis the complex process of reproduction is regulated--at least in part--by a set of neuropeptides which are encoded by a small multigene family, viz. the caudodorsal cell gene family. PMID- 2601860 TI - Nerve growth factor affects uninjured, adult rat septohippocampal cholinergic neurons. AB - The effect of nerve growth factor on the intact versus injured septohippocampal cholinergic system of adult rats was studied. Nerve growth factor was continuously infused into the lateral ventricle of adult uninjured rats or rats that had received unilateral partial transection of the fimbria. Controls (operated and unoperated) received intraventricular infusion of cytochrome c. After 2 weeks of nerve growth factor or cytochrome c treatments, choline acetyltransferase and acetylcholinesterase activities were measured in the septal area and in the hippocampus (divided into dorsal, medial and ventral parts). The continuous infusion of nerve growth factor resulted in a marked dose-dependent increase of choline acetyltransferase activity in both septum and hippocampus of adult unlesioned rats. In lesioned rats the nerve growth factor treatment was capable of inducing choline acetyltransferase activity in the hippocampus of not only the lesioned but also the unlesioned side, as well as in the septal area. In addition, nerve growth factor affected choline acetyltransferase activity differently in the hippocampus of the operated side with respect to the contralateral side or in unoperated animals. The chronic infusion of nerve growth factor did not affect acetylcholinesterase activity in the septum or in the hippocampus of either lesioned or unlesioned rats. The present findings indicate that nerve growth factor is capable of modulating the function of not only damaged but also normal adult forebrain cholinergic neurons. This suggests that nerve growth factor may modulate the function of these neurons in adulthood. PMID- 2601861 TI - Physical activity, smoking, alcohol consumption, body mass index, and plasma lipid profiles of military reserve officers. AB - We assessed the physical activity level, smoking habits, alcohol consumption, ponderosity, and plasma lipid profiles of 688 middle-aged male reserve officers. When adjusting for Body Mass Index (BMI), individuals who reported physical activity of three or more times per week had significantly higher levels of high density lipoprotein cholesterol (HDL-C), lower total cholesterol (TC) to HDL-C, and low density lipoprotein cholesterol (LDL-C) to HDL-C ratios than inactive individuals of similar age and body weight. Triglyceride, TC, and LDL-C concentrations were similar in both active and inactive subjects. PMID- 2601862 TI - [Autotransfusion protocol for patients undergoing elective orthopedic surgery]. AB - After reviewing the advantages of self-transfusional techniques, experience with 136 patients undergoing elective surgery is reported. In all cases treated, transfusional support was completely autologous, with a readily understandable saving in bank blood. Cases examined also show that sel-transfusional techniques represent an effective precautionary measure against thromboembolic complications and blood-related pathologies. PMID- 2601863 TI - [Antiemetic effect of the levo isomer of sulpiride (L-sulpiride) in humans]. AB - Vomiting represents one of the most dangerous complications of general anesthesia. L-sulpiride has been able to control this complication very effectively. We studied the effect on vomiting of two doses of L-sulpiride (50/100 mg). Both these doses have been effective in reducing the episodes of vomiting other than in preventing nausea and retching if considered versus controls and also versus droperidol at the doses of 5 mg (50 mg L-sul = 12%, 100 mg = 4%, droperidol = 20%, controls = 28%). L-sulpiride is an antagonist of dopamine on D2 receptors therefore inhibits the action of dopamine increasing the secretion of prolactin. During the surgical distress per se prolactin levels are increased. Together with the increment of catecholamines, high concentration of prolactin can evoke arrhythmias. In view of this possibility we studied the time course of the administration of the two doses of L-sulpiride and of droperidol on prolactin secretion. Both of the drugs increased the plasma levels of prolactin. Droperidol-induced increase in prolactin secretion was significant already at ten minutes after the administration reaching the peak after 20 minutes. L-sulpiride increased prolactin secretion reaching the maximum increase 20 minutes after the administration of 50 mg of the drug, and 30 minutes after the administration of 100 mg doses. The hyperprolactinemizing action of droperidol lasts for at least 8 hours, whereas L-sulpiride action lasts 4 hours. PMID- 2601864 TI - [Accidental catheterization of the subdural space. Description of 2 cases]. AB - Two cases of accidental subdural catheterisation, occurred in cancer patients during pain treatment, are presented and radiographically confirmed. The possible mechanisms that can cause such malposition, the X-ray picture and the effect of subdurally injected morphine are discussed. PMID- 2601865 TI - [Erosive-hemorrhagic duodenitis: natural history and management]. AB - A group of 32 patients with erosive-haemorrhagic duodenitis or EHD (group 5) was followed up for 36 months in order to monitor the natural history of EHD and any connections with peptic ulcers. The control group (group C) was formed of patients with similar clinical symptoms but an endoscopic picture of either a healthy duodenum or only superficial mucosal damage (non-erosive-haemorrhagic duodenitis or NEHD). The follow-up clinical, secretory and endoscopic examinations annually or whenever there were new acute attacks revealed a far higher incidence of peptic ulcer in group S than group C or in the population as a whole. The study also revealed that there is not always a link between the clinical symptoms and the severity of the endoscopic picture. It is therefore concluded that EHD patients constitute a subclass that should be kept under surveillance and given the same management as duodenal ulcer patients. PMID- 2601866 TI - [Evaluation of a colorimetric enzymatic procedure for determining the total bile acids in the blood]. AB - A simple enzymatic colorimetric procedure for the total serum bile acids determination was evaluated. In 518 normal patients values of statistical analysis ranged from 0.60 to 7.75 mumol/l (mean = 3.38 and S.D. = 2.00). PMID- 2601867 TI - [Endoscopic sphincterotomy in acute biliary pancreatitis]. AB - Six patients, 4 females and 2 males, mean age 58 (range 30-75) underwent an early endoscopic sphincterotomy because of acute pancreatitis. Serum amylases were 8N in 4 patients and greater than 20N in 2 cases. Ranson's criteria average was 2.2 for each patient. Ultrasonography showed gallbladder stones in 4 patients (2 patients underwent previously a cholecystectomy), choledochal stones in 1 patient, dilatation of main bile duct in 2 patients. Meteorism hid bile duct in 3 cases and pancreas in 5 cases. Duodenoscopy showed: papilla obstructed by gallstones in 2 patients, bulging intramural common bile duct in 2 patients; outlet of microstones and pus from papilla in 1 patient and in 1 case outlet of pus from papilla. Papillary obstruction was due to impacted stones in 4 patients, microstones in 1 patient and benign papillary stenosis in 1 patient. We performed standard sphincterotomy 3 times and in 3 patients we had to perform infundibolotomy. After endoscopic sphincterotomy and stones extraction, all the patients improved quickly and biochemical signs become normal in few days. We must not report any complication. PMID- 2601868 TI - [Cytoprotective effect of rosaprostol during treatment with non-steroidal anti inflammatory agents in arthrorheumatic pathologies]. AB - A clinico-endoscopic study has been carried out in a group of 22 patients treated with 1 g of naproxene + 2 g of rosaprostol compared in a blind situation with another group of 19 patients treated with a similar dose of naproxene + placebo in order to evaluate the cytoprotective action of rosaprostol. Analysis of the results showed a high correlation between intake of rosaprostol and low onset of algico-dyspeptic disturbances and mucosal lesions of some gravity, although the problem of the monitoring of patients undergoing long-term treatment with NSAID remains unsolved. PMID- 2601869 TI - [Radiologic aspects of metastasis to the colon. Description of 4 cases]. AB - The paper describes four cases of metastatic colon emphasizing its radiological aspect, represented by irregular and eccentric stenoses with stiffness and angling of the colon segments involved. In three cases, peritoneal carcinomatosis was also present and its radiological aspects (ascites, mesentery and omentum thickening, small intestine infiltration) were investigated by CT. PMID- 2601870 TI - [CT in the follow-up of rectal neoplasms]. AB - CT-scans were performed in the follow-up of 124 patients surgically treated for rectal carcinoma. CT allowed direct visualization of possible local recurrences and infiltration of neighbouring structures chiefly muscles and bones; it can also prove post surgical abscesses, metastatic spreads to lymph nodes and other structures such as liver, lung and bones; many of these lesions cannot so quickly and safely be demonstrated by other investigations. CT is also very helpful in radiation therapy planning. A CT guided percutaneous fine-needle aspiration biopsy can discriminate post surgical fibrosis from initial recurrences. PMID- 2601871 TI - [Linear bone densitometry by monochromatic photon absorptiometry. A study of a normal population in Apulia]. AB - An epidemiological survey was conducted on a group of Apulian residents in order to compare the densitometric data obtained with those produced by other European and North American authors. The results confirm the need for personal data on our own population given the often significant differences in order to avoid errors in monitoring patients who may require even long-term treatment. PMID- 2601872 TI - [Uric acid analysis in thalassemia trait carriers]. AB - The results of a uric acid analysis on Beta Thalassaemia Heterozygotes compared with healthy or microcytic non Beta Thalassaemia Heterozygotes are reported. Identical uric acid levels, higher than in the control group, were found in Beta Thalassaemia Heterozygotes: therefore the difference does not appear to be specific for thalassaemic carriers but consequent to increased erythrocytic catabolism in microcytic anemias. PMID- 2601873 TI - [Digestive endoscopy in the diagnosis of upper gastrointestinal hemorrhage. A retrospective study of 340 cases]. AB - After a short examination of data in the literature, the paper presents a retrospective analysis of 340 patients who underwent endoscopic examination for upper gastrointestinal haemorrhage. Among them, 123 underwent emergency and 112 elective endoscopy. A source of active or recent bleeding was identified in 87.5% of the cases. Emergency endoscopy showed a clearcut diagnostic superiority over elective endoscopy, and endoscopy as a whole was more efficient than conventional radiology. The most commonly observed bleeding lesions were found in the duodenum and stomach followed by oesophageal varices. The value of an early endoscopic approach to the diagnosis and treatment of upper gastrointestinal haemorrhage is confirmed. PMID- 2601874 TI - [Spontaneous pneumothorax in patients with osteosarcoma treated by combined chemotherapy]. AB - A report is presented on 5 cases of pneumothorax which occurred during chemotherapy in patients suffering from osteogenic sarcoma of the extremities. None of them presented radiographically detectable substitutive pulmonary lesions. It was hypothesised that the origin of pneumothorax was the necrosis produced by agents of a pulmonary micrometastasis. PMID- 2601875 TI - [Physician-patient relations in rheumatology]. AB - In a further attempt to tackle the question of the doctor-patient relationship in rheumatology, this time more comprehensively and from a different angle, the mistakes a doctor may make in daily practice are indicated. In effect, since the doctor's himself a kind of "drug", only his "correct administration" will effectively solve certain of the patient's psychological problems. PMID- 2601876 TI - [Primary myxedema in an adult. Notes on a case]. AB - In the case of adult primary myxedema reported the diagnostic suspicion aroused by objective examination was confirmed by assaying the hypophysial-thyroid hormones (blood T4 and T3 below normal levels) and by the behaviour of certain muscle enzymes (CPK, LDH, GOT) that bore witness to diffuse muscle and bone damage (hypothyroid "myopathy"). The presence of antithyroid antibodies, though in small amounts suggested earlier and unnoticed thyroiditis as a possible aetiopathogenic explanation. The clinical and metabolic picture undoubtedly benefited from treatment with L-Thyroxine. PMID- 2601877 TI - [A case of pericarditis in acute brucellosis]. AB - A case of brucellosis pericarditis in a patient affected with acute brucellosis hospitalized in the Infectious Disease Department of Asti Hospital is described. During the hospitalization, the patient revealed (in addition to the classical symptoms and signs), a modest shooting pain in the chest and typical electrocardiographic alterations confirmed by an echocardiography that revealed slight pericardial effusion at both front and rear, subsequently and by steroid and specific antibiotic therapies. The real possibility of finding this complication, considered so rare in the literature, in cardiovascular brucellosis is pointed out as is the capacity of modern echocardiographic research to confirm and reinforce diagnosis and consequently also the description of modest pericardial effusions with unclear symptoms and electrocardiographic signs that were once practically ignored when the pericardial involvement often escaped a clinical identification, being concealed by the most important signs of the primary infection. PMID- 2601878 TI - [A case of Ramsay Hunt syndrome]. AB - We describe a clinical case of RH syndrome (Auricular Herpes zoster, facial paralysis, hearing loss). PMID- 2601879 TI - Stimulus access to olfactory and vomeronasal receptors in utero. AB - Chemosensory systems in the mammalian nasal cavity are said to be functional before birth. Fluorescent beads (1 micron, diameter), injected into the amniotic fluid surrounding E18 mouse fetuses, were sought in serial frozen sections of E19 animals. Beads were found in all regions of the nasal cavity except for the lumen of the vomeronasal organ (VNO) where the receptor neurons of the accessory olfactory system (AOS) are located. Thin plastic sections through the rostral aspect of the E19 nasal cavity revealed that the VNO canals, which provide stimulus access to the AOS, are not patent. Thus, this chemosensory system can be excluded as a potential channel of chemosensory information for the mouse fetus. PMID- 2601880 TI - Do the ependymal cells contain vasoactive intestinal polypeptide? AB - Immunoreaction for vasoactive intestinal polypeptide (VIP) in the ependymal cells was investigated using two different commercially available polyclonal antisera for VIP. Immunostaining with an anti-VIP serum showed strong reaction products in the ependymal cells of the central canal and the third ventricle, in addition to immunoreactive neuronal elements in the spinal cord and in the suprachiasmatic nucleus. Staining of the ependymal cells was not reduced by preabsorption of the antiserum with synthetic VIP, while the immunoreactive neuronal elements disappeared. Such staining of the ependymal cells was not found using other antiserum. PMID- 2601881 TI - Evidence for three morphological classes of astrocyte in the adult rabbit retina: functional and developmental implications. AB - Commercially available antibodies to glial fibrillary acidic protein (GFAP) and vimentin were used in conjunction with our own antibodies (3F11, MA1 and 4D6) to label astrocytes in the adult albino rabbit retina. Anti-GFAP labels the entire astrocyte population and shows them to be morphologically diverse. By contrast, the remaining four antibodies label different subpopulations of astrocytes. Comparisons of the shapes and distributions of cells composing these subpopulations led us to distinguish three morphological classes: Class A are predominantly perivascular astrocytes, Class B are territorial and rarely contact vessels or axons, Class C (which seems to contain four subclasses) are astrocytes that are predominantly associated with axons. PMID- 2601882 TI - Comparison of the effects of intracerebrally administered MPP+ (1-methyl-4 phenylpyridinium) in three species: microdialysis of dopamine and metabolites in mouse, rat and monkey striatum. AB - Intracerebral microdialysis in 3 awake species allowed the measurement of the basal output of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) from rat and mouse striatum and monkey caudate in vivo. The DOPAC/HVA ratios in dialysates from mouse and rat striatum were about 1 and 2 respectively, but only 0.09 in monkey caudate dialysates. The extracellular levels of the metabolites correlated well with reported tissue levels, while extracellular DA levels were 3 orders of magnitude lower than tissue concentrations. The effects of the intracerebrally administered dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+) were essentially similar in the 3 species. In all cases an immediate, massive release of DA was accompanied by a pronounced decrease in the output of the metabolites. Basal DA release was no longer detectable 5-12 h after MPP+ administration and a second MPP+ perfusion failed to increase the release of DA. PMID- 2601883 TI - Exogenous GM1 gangliosides induce partial recovery of the nigrostriatal dopaminergic system in MPTP-treated young mice but not in aging mice. AB - The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to young (2-3 months) and aging (12 months) C57BL/6 mice (4 x 20 mg/kg, i.p., given 12 h apart) reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum, and reduced dopamine (DA) concentration to 28% of controls in young, and 16% of controls in aging mouse brain five weeks after administration. Although GM1 ganglioside treatment (30 mg/kg, i.p., daily for 5 weeks) restored striatal dopamine concentration to 74% of the control concentration in young mice, such an apparent recovery was not seen in aging brain. Immunocytochemical analysis also showed marked recovery of TH-IR fibers in the striatum of MPTP depleted young mice treated with GM1 ganglioside while TH-IR fibers in the striatum of MPTP-depleted aging mice showed no recovery with such treatment. We conclude that treatment of MPTP-depleted young mice with GM1 ganglioside results in partial recovery in the striatal DA system, but such benefits do not extend to aging mice. PMID- 2601884 TI - Millimolar concentrations of free magnesium enhance exocytosis from permeabilized rat pheochromocytoma (PC 12) cells. AB - The role of Mg2+ during the final steps of exocytosis was investigated using rat pheochromocytoma cells (PC12) permeabilized with bacterial pore forming toxins. Concentrations of free Mg2+ between 0.2 and 2 mM slightly lowered the basal but greatly enhanced the [3H]dopamine release elicited by 8 microM free Ca2+. Maximal effects were obtained at approximately 1 mM free Mg2+. At higher concentrations Mg2+ was less potent. Similar effects of Mg2+ were obtained in cells permeabilized either for small molecules (by alpha-toxin) or for large ones (by streptolysin O). It is concluded that millimolar concentrations of cytoplasmic Mg2+ play an important role in Ca2+ triggered exocytosis. PMID- 2601885 TI - Chloride and magnesium dependence of vasopressin release from rat permeabilized neurohypophysial nerve endings. AB - The role of Cl- and Mg+ ions has been studied on the secretory mechanism leading to the release of vasopressin from digitonin permeabilized nerve endings isolated from the rat neurohypophysis. Secretion was triggered by challenging the permeabilized nerve endings with 1.1 microM free Ca2+. Magnesium enhances secretion and its maximal effect occurred at a concentration of about 2 mM. Further increase of this divalent cation concentration however led to an inhibition of secretion. Chloride ions are necessary for the final steps in exocytosis and this effect of Cl- was inhibited by the chloride channel antagonist N144. It is concluded that in neurosecretory nerve endings magnesium and chloride ions are crucial components for exocytosis to occur. PMID- 2601886 TI - Intracellularly injected inositol hexakisphosphate induces a biphasic current in identified neurons of Aplysia. AB - Inositol hexakisphosphate (IP6) was pressure-injected into the somata of the identified neurons (R9-R12) in the abdominal ganglion of Aplysia. Intracellular injection of IP6 into a neuron voltage-clamped at -45 mV reproducibly induced a biphasic membrane current consisting of an inward current (Ii(IP6)) followed by a slow outward current (Io(IP6)). Conductance is increased at the peaks of these currents. The extrapolated reversal potential of Ii(IP6) was -34 mV, whereas Io(IP6) was increased by depolarization and decreased by hyperpolarization up to 75 mV, where it disappeared. Ion substitution and pharmacological experiments suggest that microinjection of IP6 into the Aplysia neurons activates two or more separate types of ion channels. PMID- 2601888 TI - Adenosine analogs elevate N-acetylserotonin and melatonin in rat pineal gland. AB - Adenosine, S-adenosyl-L-homocysteine, adenosine analogs such as 5'-N ethylcarboxamidoadenosine and mioflazine, a nucleoside transport inhibitor, injected intraperitoneally at 09.00 h during the light period increased melatonin levels in the pineal gland of the rat. The largest increase occurred with 1 mg/kg 5'-N-ethylcarboxamidoadenosine. A representative time-response curve with 5'-N ethylcarboxamidoadenosine (1 mg/kg) showed a maximal peak of N-acetylserotonin and melatonin 2 and 4 h after injection, respectively. These results are discussed in relation with the possible modulation through A2 receptors of melatonin synthesis in the pineal gland. PMID- 2601887 TI - Effect of cold stress on cholinergic receptors in the rat adrenal gland. AB - The effects of cold exposure on cholinergic binding sites in the rat adrenal gland were assessed by examining the binding of [125I]alpha-bungarotoxin (BTX), a nicotonic receptor antagonist and [3H]quinuclidinyl benzilate (QNB), a muscarinic receptor antagonist, to adrenal tissue homogenates. Cold exposure resulted in significant alterations in both nicotinic and muscarinic binding. Exposure to cold for 4 and 7 days resulted in a significant decrease in QNB binding. Scatchard analysis indicates that this alteration is due to a decrease in binding sites (Bmax) rather than a change in ligand affinity (Kd). In contrast, chronic cold exposure produced a significant increase in BTX binding sites. These results indicate that adrenal cholinergic receptors are altered in reciprocal fashion by chronic cold exposure, and that this change may represent a key event in the sympathoadrenal system's adaptive response to chronic cold stress. PMID- 2601889 TI - Human postural reflexes and gravity--an under water simulation. AB - This study represents the first attempt to investigate the influence of gravity on postural adjustments. Subjects were displaced while standing under water on a movable platform, while the buoyancy of the body was adjusted by using a variety of lead vests. Under water, an approximately linear relationship was found between body weight and impulse directed electromyographic response amplitudes in the leg and thigh muscles. Loading of the subjects out of water resulted in a saturation of the response amplitude. The biomechanical signals recorded during the displacements indicated that neither vestibulospinal nor muscle proprioceptive reflex mechanisms can account for the effect observed under water. It is suggested that the EMG responses are mediated by reflexes which are activated by pressure receptors within the body in order to hold the centre of gravity over the feet. PMID- 2601890 TI - And then my friend died. PMID- 2601891 TI - Cooperative care. PMID- 2601892 TI - Critical care nursing in baccalaureate programs. AB - There is a need to resolve several issues related to inclusion of CCN in the baccalaureate curriculum. These include: (1) the nature of specialist versus generalist preparation; (2) the goals for inclusion of CCN, (as well as content related to any other area of practice which may be considered specialized); (3) the relationship between education and practice, and the responsibilities of each in educating competent practitioners to provide safe care to critically ill patients. PMID- 2601893 TI - On the fast track. AB - Future nursing programs will be flexible, meeting the learning needs of diverse student populations. Feldman and Jordet describe an accelerated BSN track for nonnurse college graduates that meets that objective. In 3 years of experience with the program, the authors found these adult learners to form cohesive student cohorts and to produce strong graduates. In spite of the highly compressed 1-year program of studies, the project is deemed a success; a high dropout rate is more than compensated for by the high grade point average and the 100/N-CLEX examination pass by graduates. An extraordinary number of graduates intend to pursue graduate study. PMID- 2601894 TI - Nonnurse college graduates in a specialty master's program: a success story. AB - Flexibility and diversity will characterize nursing education in the future. Smith presents one option whereby nonnurse baccalaureate graduates get their first nursing degree at the master's level. In this 3-year program, the first year focuses on junior level courses, the second year gives accelerated senior and graduate level content, and the third year provides the master's level clinical specialty. The success of the program validates the curriculum model and the rich capacity of students to learn effectively in programs of all sorts. PMID- 2601896 TI - Physical fitness and basal metabolic rate. PMID- 2601895 TI - A comparative study between interactive television and traditional lecture course offerings for nursing students. AB - Nursing education of the future will be characterized by diverse teaching methods. New modalities will be tested and used to meet constraints on both teachers and students. Parkinson and Parkinson report on the use of interactive television as a medium of education for nursing students studying pathophysiology. They compare this method to the more traditional teacher lecture method with interesting results. While students may prefer the human interaction, the learning results may be equivalent when the alternative medium is used. PMID- 2601897 TI - Senile cataract and vitamin nutrition. PMID- 2601898 TI - Failure to maintain weight loss: permissive role of lipoprotein lipase. PMID- 2601899 TI - Does tissue glutathione level indicate organ senescence? PMID- 2601900 TI - Retinoic acid and thyroid hormone regulate gene expression through a common gene element. PMID- 2601901 TI - Aging and dietary fat and cholesterol transport. PMID- 2601902 TI - Primary care diagnosis and management of Bell's palsy. AB - Bell's palsy, an idiopathic facial paralysis of the seventh cranial nerve, is an important entity for clinicians to identify early because prognosis is more favorable with early intervention. Although the etiology is unknown, recent studies have indicated a familial tendency and increased incidence in patients with a history of diabetes, arterial hypertension and serum lipid disturbances. The specificity and severity of signs and symptoms are determined by the facial nerve fibers affected. Various diagnostic tests become an important factor in determining not only the differential diagnoses but also the severity of the occurrence and the prognosis for recovery. PMID- 2601903 TI - Erectile dysfunctions: assessment and care. AB - Erectile dysfunction is a common sexual problem for males in the United States. Health care practitioners need to consider sexual concerns as part of their holistic approach to clients who have sexual problems. This article examines the etiology, assessment and treatment of erectile dysfunctions in the heterosexual male. Physical and psychological influences on erectile dysfunctions are discussed. History-taking, including sexual history, physical assessment and common diagnostic tests, are described for the practitioner who is caring for the sexually dysfunctional client. General treatment modalities and referral needs are discussed. PMID- 2601904 TI - Sexual assessment and the aging female. AB - Due to an increasing population of elders, more women are in need of geriatric gynecologic care. Many of these women are capable of being active sexual partners throughout their lifetimes. However, there are a number of factors that can influence sexual relationships, including personal and societal values, the normal physiologic changes associated with aging and the availability of a sexual partner. Obtaining accurate histories and appropriate physical data regarding sexual functioning are important. Measures that will aid the collection of a complete database, along with pertinent physical assessment, are discussed. Options for treatment and education of the elderly woman in the area of sexual needs are presented to assist health care providers in their role as sex educators and counselors for older women. PMID- 2601905 TI - Nurse practitioners: factors affecting role performance. AB - This descriptive, correlational investigation was designed to examine the attitudes/values held by nurse practitioners concerning their roles, self assessment of their skills/knowledge, and orientation toward a nursing or medical model to guide practice. The results indicate that the nurse practitioners in this sample have a high degree of confidence in their skills and knowledge and have a fairly strong nursing orientation in their practice. The great deal of variability in responses to items concerned with audit, quality assurance and financial aspects of the role have important implications for nurse practitioner education and practice. PMID- 2601906 TI - 'Caveman diet' and Candida worthy of attention. PMID- 2601907 TI - CCNP shares NP salary survey results. PMID- 2601908 TI - Recognising CNS infections. PMID- 2601909 TI - Psychological care before brain surgery. PMID- 2601910 TI - One nurse's view of ambulancemen. PMID- 2601911 TI - Come back nurse--please! PMID- 2601912 TI - The need to talk. PMID- 2601913 TI - HIV and encephalopathy. PMID- 2601914 TI - Meningitis and the child. PMID- 2601915 TI - Association & Union: 1 big happy family? PMID- 2601916 TI - Association & Union: 1 big happy family? Nurses' views. PMID- 2601918 TI - National action campaign to save our public health service: Action! PMID- 2601917 TI - Of waste & waiting lists. Interview by Lyndon Keene. PMID- 2601919 TI - A question of quality. PMID- 2601920 TI - The Nurses' Act--what's in it for you? PMID- 2601921 TI - New ways with old style. PMID- 2601922 TI - So you want to nurse abroad? PMID- 2601923 TI - Busy in the beehive. PMID- 2601924 TI - Breast milk--still more data required. PMID- 2601925 TI - Radionuclide methodology for the assessment of the microcirculation in island pedicle flaps in a sheep model. AB - Island pedicle flaps with a proximal well-perfused part and a distal poorly perfused part were raised in eight anaesthetized sheep. Autologous red blood cells were labelled in vitro with 99TcmO4 and plasma with 111In chloride. The labelled cells and plasma were injected intraarterially and both dynamic and static images of the time-course of radioactivity were obtained with a gamma camera. Time activity curves were generated for selected regions of interest of the flap. For both plasma and red cells there was a substantial decline in the amount of tracer reaching the distal part of the flap; the time to maximum counts increased and the time activity curves indicated a minor uptake and almost no clearance pattern. In general there were marked local differences in the flow of plasma and red cells. The flow of plasma was more rapid than that of the red cells in five of the eight sheep. The model provides a standardized pedicle flap having a proximal part with adequate circulation and a distal part with inadequate circulation. It is concluded that this sheep model is suitable for radionuclide studies examining those factors that influence the distribution of blood flow within this tissue. PMID- 2601926 TI - Nurse stuck with HIV-infected needle. PMID- 2601927 TI - Study indicates smoking cessation improves workplace absenteeism rate. PMID- 2601928 TI - Peer assistance program in Ohio--happy 10th birthday to special volunteers. PMID- 2601930 TI - Balancing the evaluation. PMID- 2601929 TI - "Genericgate". PMID- 2601931 TI - On cholesterol testing of children... PMID- 2601932 TI - Guidelines for physicians of athletic teams. PMID- 2601933 TI - AMA forms department for foreign medical graduates. PMID- 2601934 TI - Alzheimer's disease: are we making any progress? PMID- 2601935 TI - Malpractice: is physician support failing? PMID- 2601936 TI - The durable power of attorney for health care. PMID- 2601937 TI - Cinderella dermatosis. PMID- 2601939 TI - Steps toward more defensible medical records. PMID- 2601938 TI - Organized medicine and its value to medical students. PMID- 2601940 TI - Asymptomatic Chlamydia infection in pregnant women. AB - Chlamydia trachomatis infection is currently among the most prevalent sexually transmitted diseases in the United States. A review of three textbooks of obstetrics reveals that none of them recommend routine chlamydia screening in prenatal patients, although two recommend routine screening for gonorrhea. A study was done at the Barberton Citizens Hospital Family Practice Residency Program to determine the incidence of asymptomatic chlamydia infection in pregnant women and to compare this to the incidence of asymptomatic Neisseria gonorrhoeae infection in the same population. A total of 69 patients were screened for Neisseria gonorrhoeae and Chlamydia trachomatis as part of their routine prenatal evaluations at the first prenatal visit and the visit of 36 weeks gestation. Neisseria gonorrhoeae was detected by growth on standard Martin Lewis culture plates. Chlamydia trachomatis was detected by positive immunofluorescence using a standardized specimen kit (Syva Company, Palo Alto, California). The data were collected over a 12-month period from July of 1987 through July of 1988. There were no positive cultures for Neisseria gonorrhoeae (0%) in this group of patients. On the other hand, five patients tested positive for Chlamydia trachomatis (7.2%). The results of this study indicate that routine screening for Chlamydia trachomatis should be considered as part of the routine prenatal care. A larger, multi-centered study could be done in the future to confirm these results, as well as to determine if any regional differences exist. PMID- 2601941 TI - On the variations of the time constant of the slow-phase eye movements produced by surgical therapy of congenital nystagmus: a preliminary report. AB - Quantitative analyses of the effect of nystagmus surgery have been based previously on the pre- and postoperative comparison of the nystagmus intensity at various gaze angles. On the other hand, a recent hypothetical model of the defective oculomotor system producing congenital nystagmus emphasizes that the time constant of the (increasing velocity) slow-phase eye movements should represent a useful parameter in the quantification of the surgical effects, since it is related to the potential good visual acuity of the patients in the presence of nystagmic cycles with extended foveation. By computer analysis of the pre- and postoperative electro-oculographic recordings from 5 patients with congenital nystagmus we show experimentally that the above theoretical indication is a valid tool in the assessment of the effects of classic nystagmus surgery. PMID- 2601942 TI - Bound water content of bovine lens capsules. AB - The anterior parts of bovine lens capsules have been incubated in media with different glucose contents. The freezable water content of the lens capsule was obtained by differential scanning calorimetry and the total water content by thermogravimetric analysis. The bound (nonfreezable) water content was calculated as the difference between total and freezable water. The bound water as percent of the total water increases with the degree of glycosylation of the bovine lens capsules. PMID- 2601943 TI - Regional water content of clear and cataractous human lenses. AB - The present study evaluates the regional water content of clear and cataractous human lenses. In order to determine the lens water, a freeze-drying technique was used which leaves behind only a very small amount of residual humidity. The effectiveness of freeze-drying was demonstrated in experiments with animal eye lenses (rat, pig, bovine). The results obtained revealed that, like in other mammalian lenses, the human lens cortex exhibits a significantly higher overall water content than the nucleus. This pattern was found in clear lenses as well as in lenses with early 'senile' cataracts. Subcapsulary cataracts present a unique feature as in these lenses the cortical water content is enhanced while the fresh lens weight is significantly reduced. Observations of postmortem human eye lenses indicate that regional differences in water content are greatly abolished 24-48 h after death. PMID- 2601944 TI - Growth of an ocular strain of Chlamydia trachomatis on Chang conjunctival cells. AB - The most widely used cell lines for in vitro studies of Chlamydia trachomatis infections are McCoy and HeLa cells. Our understanding of the intracellular events that occur during ocular C. trachomatis infections may well be improved if such infections could be studied in a host cell that more closely approximates the natural host conjunctival cell. We report here that Chang conjunctival cells, which have been derived from human conjunctival cells, can be infected with C. trachomatis, serovar B. The optimal times for exposure of the host cells to infectious material and to cycloheximide are about 24 and 48 h, respectively. Under these conditions, the maximum number of inclusions is observed at 72 h after centrifugation. PMID- 2601945 TI - [Radical transurethral resection of bladder tumors]. AB - During the last ten years the authors treated 462 bladder tumors of 319 patients in the expectation of radicality. On the basis of histopathological examination following TURs with differenciating technique the tumor-removing proved true in the cases of 360 tumors (78%). The first TUR was radical only in 65% of the tumors, in 10% the second, in 2% the third and in 1% the fourth intervention resulted full radicality. The authors analyse the number of TUR's needed to complete removing of tumors in connection with the depth of infiltration and the configuration of tumors. The exploration of the causes of failure makes possible the improvement of the results. PMID- 2601946 TI - [Routine roentgen examination of the skull in head injuries]. AB - Authors in their present report are studying the routine skull X-ray examination of head injured patients. They discuss the disadvantages of the routine up to the present. They introduce the classifications found in the literature. With the help of these classifications the injured who do not need skull X-ray examination can be separated. In case of hospitalisation they consider the anamnesis and clinical examination to be primary in contradiction to the X-ray result. They introduce the retrospective results their head injured patients treated between 1977-1986 in their department. PMID- 2601947 TI - [Routine two-dimensional roentgen studies in head injuries]. PMID- 2601948 TI - [Thoughts on changes in the health care system of Hungary]. PMID- 2601949 TI - [Sex determination of the embryo by DNA studies of chorionic villi samples]. AB - The first step in the prenatal diagnosis of X-linked genetic disorders is the determination of the sex of the fetus. A new method for this purpose is based on recombinant DNA technology. The authors give a short account on their experiences with a Y specific DNA probe. Fetal DNA was prepared from chorionic villi taken at the 8th-12th weeks of gestation. The DNA was hybridised with the Y specific probe. This probe was isolated from the 3,4 kilobase human repeat sequence derived from heterochromatin of the Y chromosome and had 1000 times more affinity for male DNA than for female DNA. The method based on hybridisation with the Y specific probe should facilitate first-trimester prenatal sex determination of X linked genetic disorders. PMID- 2601950 TI - [Antithrombotic therapy in ischemic heart disease]. PMID- 2601951 TI - [Guidelines to the current drug therapy of hypertension. (Amendment to the 1988 decision of the Committee on Hypertension of the National Health Council)]. PMID- 2601952 TI - [Where should children with purulent meningitis be treated?]. PMID- 2601953 TI - [Prenatal lead blood levels in a city heavily exposed to lead]. AB - The blood lead concentrations were measured in 38 pregnant women and their newborn babies in a high exposure area. The lead content of human milk was also determined on the 5th day after delivery. The blood lead concentrations were higher than 12 micrograms/100 ml in more than 80 per cent of the samples. The lead content of breast milk was also greater than those of published recently. We found a strong correlation between the blood lead levels of the mothers and the newborns. There was a moderate correlation between the lead concentrations in the blood and the breast milk. PMID- 2601954 TI - [Founding of the Hungarian Chamber of Physicians]. PMID- 2601955 TI - [The ownership of radiographs and radiologic records]. PMID- 2601956 TI - [Bone scintigraphy in uremic osteodystrophy]. AB - 99mTc-HEDP bone scan was carried out on 12 long-time haemodialysed patients, suffering from bone pains. X-ray examinations of the bone and laboratory tests (serum calcium, -phosphor, -alkaline phosphatase, -parathormone, -aluminium, ferritin) were also performed. The scintigrams were evaluated by two semiquantitative scores. Based on diffuse, increased radiopharmacon uptake of the bones and more than five points in the Fogelman score 5 patients most likely had serious and 3 had moderate hyperparathyroidism. In two patients osteomalacy was presumed based on decreased radiopharmacon uptake of the bones, increased uptake of the soft tissues and zero Fogelman score. Mixed or other bone disease was suggested in two other patients. Good correlation was found between the results of bone scans, the parathormone values and the results of histology obtained after parathyreoidectomy of 4 patients and autopsy of two others. This non invasive examination (ie. bone scan) is helpful in differential diagnosis of uraemic osteodystrophy and its wide use is proposed in domestic nephrological practice. PMID- 2601957 TI - [Adult prognosis of infantile obstructive bronchitis]. AB - The authors made a followup study of 0-36 months old patients admitted with the diagnosis of obstructive bronchitis to the Komarom City Hospital's Pediatric Department. Eighty eight patients were explored at the age of 23-26 years with the use of questionnaires. Four of these (4,54%) are still under active treatment because of bronchial asthma. This--taking into consideration the prevalence of adult asthma--shows the connection of these disease entities. PMID- 2601958 TI - [Severe tracheal compression caused by achalasia]. AB - A very rare complication of achalasia (cardiospasm) is presented. In the authors' case the esophagus of a 15-year old girl was dilated to a great extent and caused through the compression of the trachea upper respiratory obstruction. Following the surgical solution of the achalasia the respiratory complications ceased too. Attention is drawn to the possibility that esophagus diseases may play a significant role in the etiology of different pulmonary diseases. PMID- 2601959 TI - [The question of teaching Latin at medical schools]. PMID- 2601960 TI - [Special training at the university--an utopia?]. PMID- 2601961 TI - [The science of nursing: a university education in Austria. Preliminary considerations and current situation]. PMID- 2601963 TI - [Correct communication with blind patients]. PMID- 2601962 TI - [Skin tolerance of alcoholic disinfectants for sanitary hand disinfection]. PMID- 2601964 TI - [Problems of nurses in the surgical service]. PMID- 2601965 TI - Headache and facial pain. PMID- 2601966 TI - Keeping up with sexually transmitted diseases. PMS Commission on Public Health and Toxic Substances. PMID- 2601967 TI - Cervical cancer study using the Cancer Registry. PMID- 2601968 TI - HIV transmission among heterosexuals. PMID- 2601969 TI - PNA urges House Committee's support of AIDS legislation. PMID- 2601970 TI - Someone they love is dying. PMID- 2601971 TI - Notes from the International Research Congress in Taipei. PMID- 2601972 TI - ANA opposes RCT training program planned for Louisville. PMID- 2601973 TI - House Bill 121--Auto Insurance Reform Bill. Who does it help? Who does it hurt? PMID- 2601974 TI - Interpretation of HCFA rule leaves New Mexico elderly and poor without care: passage of Rural Nursing Incentive Act (S.1384) would remedy situation. PMID- 2601975 TI - Serum lipoperoxide levels in pregnancy induced hypertension. AB - With present day awareness of role and toxicity of lipid peroxides, serum levels of lipoperoxides have been investigated in forty pregnancy induced hypertension (PIH) subjects, before and after antihypertensive drug therapy, using full term normotensive patients as control. PIH subjects demonstrated highly significant elevated serum levels of lipoperoxides (mean 3.60 nmol/ml) in comparison (mean 2.15 nmol/ml) with full term normotensive subjects. At post-partum PIH subjects following antihypertensive drug therapy and becoming normotensive showed highly significant fall in serum lipoperoxide (mean level 2.27 nmol/ml). Full term normotensive subjects at post-partum also demonstrated the same pattern. However, observed levels of serum lipoperoxide in PIH subjects at post-partum even after becoming normotensive following treatment were found to be significantly elevated when compared with those of full term normotensives at post-partum (mean level 1.94 nmol/ml). It is felt that monitoring of serum lipoperoxide level can serve as one of the useful parameters in PIH subjects. PMID- 2601976 TI - Day-time changes for pituitary-thyroid hormones denote a rhythmic structure not detectable in elderly subjects. AB - The day-time concentrations of TSH, T3, T4, FT3 and FT4 were investigated in clinically healthy volunteers, 20 young individuals, aged from 20 to 27 years, and 12 elderly subjects, aged from 70 to 81 years. Nocturnal sampling was purposely avoided in order to eliminate the interindividual differences in sleep patterns. The day-time series were analysed by means of cosinor analysis to interpolate the best-fitting sinusoidal wave that covers the day-night period. The reconstruction of the circadian sinusoidal wave was validated for TSH, T3, T4, FT3 and FT4 in young subjects, and, with limitation, for T4 in elderly individuals. The findings suggest that the day time patterns of TSH, T3, FT4 and FT3 in elderly subjects are characterized by a dyschronism that is not detectable in young subjects. The investigation of the day-time concentrations is suggested as a cost-effective tool for exploring the circadian cycle of the pituitary thyroid hormones in aged people. PMID- 2601977 TI - Tuberculosis of the larynx. Today. AB - Forty-one cases of laryngeal tuberculosis accounting for 0.79% of the TB cases observed in 1975-85 are examined. The M/F ratio was 9.2:1; the mean age 52 years 9 months. In all cases current or earlier tubercular lesions on the pulmonary parenchyma were also noted. The laryngeal sites affected were as follows, in order of frequency: true vocal cords, epiglottis, false cords and laryngeal ventricles, arytenoid and interarytenoid area, subglottic area. The patients were treated with R/AMP, INH, EMB or SM, EMB with satisfactory results. Two cases required exeresis of laryngeal lesions and 3 tracheotomy. PMID- 2601978 TI - Anti-HIV and anti-HBc antibodies and HBsAg in postmortem blood of drug addicts: the picture for 1988. AB - Serological markers of HIV and HBV infections were studied in 90 drug addicts who died in 1988 and were medicolegally autopsied at the Institute of Forensic Sciences, University of Turin. Nineteen (21.1%) displayed evidence of HIV infection, demonstrated by the presence of anti-HIV antibodies; fifty-nine (65.5%) HBV infection, demonstrated by the presence of anti-HBc antibodies and/or HBsAg; nine (10%) had HBsAg, indicating potential infectiousness for HBV infection. PMID- 2601979 TI - Neoplastic thrombosis of the inferior vena cava and right atrium due to kidney cancer. Three surgically treated cases. AB - Extension into vena cava and right atrium of tumor thrombus from a renal cell carcinoma presents a surgical challenge. The use of cardiopulmonary by-pass, hypothermia and cardiac arrest with temporary exsanguination has allowed the successful surgical excision of this tumor. During 1986 and 1987 3 patients with cancer of kidney invading the vena cava were operated on with this surgical technique. No deaths occurred. The possibility of curing this type of cancer with minimal operative risk and good results is discussed. PMID- 2601980 TI - Bone marrow involvement in Kaposi's disease. Report of a case. AB - A 71-year-old woman with Kaposi's sarcoma was admitted to the hospital because of severe pancytopenia with negative sternal aspirate. The bone marrow trephine biopsy demonstrated an extensive replacement of the hematopoietic tissue by Kaposi's sarcoma. Skin, soft palate mucosa, spleen, retroperitoneal and axillary lymph nodes were also found to be involved at the post-mortem examination. Therefore the bone marrow biopsy can be used in the staging of Kaposi's sarcoma in presence of pancytopenia and might be able to detect a primary visceral involvement in patients without cutaneous lesions. PMID- 2601981 TI - Hemangioma of the small bowel. Case report. AB - Cavernous hemangioma is a very rare disease if located in the ileum, but not an uncommon lesion if it occurs in the large bowel. The Authors report a case of small bowel cavernous hemangioma, and consider clinical, diagnostic and therapeutic aspects for an exact evaluation of the lesion. PMID- 2601982 TI - Thoughts about spinal actions and cerebral reflections in movement. AB - Some thoughts about the co-ordination in movement are given and how our communication organ may be able to adapt to the disaster of an interruption in the information chain. PMID- 2601983 TI - Traumatic spinal cord injuries in Greenland 1965-1986. AB - During the period 1 January 1965 to 31 December 1986, 27 patients were admitted to the Rehabilitation Hospital in Hornbaek after traumatic spinal cord injury (SCI) sustained in Greenland. The commonest cause of injury was attempted suicide (7 patients), of which 6 were jumps from buildings. Six resulted from accidental falls to a level below and even 2 out of the 3 cases of SCI following violence were due to falls. There was only one traffic injury, a motor cycle accident. Fourteen patients were under the influence of alcohol at time of injury. Nine were tetraplegic (3 complete, 6 incomplete), and 18 paraplegic (10 complete, 8 incomplete). Ten regained useful neurological remission. Of the 23 native Greenlanders only 4 paraplegics and 1 tetraplegic remained in their previous residences, 5 resettled in Denmark. At the time of follow-up 17 patients were living alone and only 7 were in work. PMID- 2601984 TI - Clinical, urodynamic and neurophysiological findings in patients with neuropathic bladder due to a lumbar intervertebral disc protrusion. AB - Sacral nerve roots are affected in 1 to 15% of reported cases of lumbar disc protrusions (mainly posterior) (Scott, 1965). Urinary retention is the commonest symptom. In the last 6 years, we have observed 22 patients (18 males and 4 females) with a neuropathic bladder due to this condition in the acute phase. They underwent intermittent catheterisation (IC), and manoeuvres such as Crede and Valsalva's at fixed times. Almost all obtained a balanced bladder. ( FOLLOW UP: 24 months.) The most common urodynamic finding at the onset was bladder areflexia with severe denervation of the perineal floor. At follow-up, 65% still had bladder areflexia and 29% normoreflexia, all with normal compliance. Perineal floor innervation showed a fair recovery, mainly in the efferent part. An hypothesis is presented to explain why this kind of neuropathic bladder has a normal compliance. PMID- 2601985 TI - Metastatic spinal cord tumours. AB - In this report 84 patients who had surgical intervention for metastatic spinal cord tumours are presented. The primary tumours were mainly from lungs, breast or of haematological origin, and were commonest in the thoracic region. In all but 2 patients laminectomy was performed. Surgical decompression permitted diagnosis, and there was neurological improvement in nearly half of the patients. PMID- 2601986 TI - The effect of verapamil on the treatment of detrusor hyperreflexia in the spinal cord injured population. AB - Verapamil, a calcium channel blocker, was tested alone and in combination with oxybutynin chloride for its clinical effectiveness in the treatment of detrusor hyperreflexia in a spinal cord injured population. Fourteen patients with detrusor hyperreflexia were included. All patients were treated with oxybutynin chloride alone and with the combination of oxybutynin chloride and verapamil. Six of the patients were also studied on no medication and verapamil alone. Cystometric and clinical comparisons were made with each change in drug dosage. Verapamil 240SL, when used alone, produced a delay in the first detrusor contraction as compared to no medication in 5 of the 6 patients but clinical improvement was insignificant. Clinical improvement with tolerable side effects was noted in 13 of the 14 patients treated with the combination of oxybutynin chloride and verapamil over oxybutynin alone. Our early experience with verapamil suggests that it may be a valuable adjunct in the treatment of detrusor hyperreflexia. PMID- 2601987 TI - Experimental studies on permeability of tracers into the spinal cord. AB - For investigation of the intramedullary penetration of metrizamide, the intramedullary movements of fluorescein, Evans Blue, Horseradish peroxidase (HRP) and ionic lanthanum in the normal cord and experimental syringomyelia of rats were studied. Syringomyelia was induced by injection of kaolin suspension into the cisterna magna. Subsequently HRP or ionic lanthanum was perfused into the subarachnoid space and its distribution was examined by electron microscopy. In normal rats, HRP mainly became localised in the basement membrane between the pia mater and glial cells and only a few vesicles migrated into the extracellular spaces (ECS) between glial cells. Ionic lanthanum, however, migrated deep into the ECS. In rats with experimental syringomyelia many vesicles of HRP migrated deep into the ECS of glial cells and the white matter. These findings indicated that the ECS of the marginal glia and the neuropil constitute part of a pathway through which metrizamide migrates into the intramedullary cavity. PMID- 2601988 TI - Motor recovery in the absence of segmental afferents: a case study of incomplete spinal cord injury. AB - A 41-year-old male with a prior left L-5/S-1 radiculopathy developed complete quadriplegia following a gunshot wound to the left anterior neck. He subsequently recovered pinprick sensation over the left side of the trunk and lower extremity; and a right peroneal SEP, suggested sparing of long tracts on the right side. Voluntary motor strength gradually recovered more on the left than right for the L-5/S-1 segments, where tendon reflexes were absent. This unique case is discussed with respect to the effect of absent segmental afferents on suprasegmental recovery. PMID- 2601989 TI - Actinomycosis as a cause of spinal cord compression: a case report and review. AB - A case is presented of a 40-year-old man with rapidly progressing symptoms of thoracic medullary compression, initially thought to be caused by metastatic pulmonary malignancy. Further investigations, however, revealed thoracic actinomycosis spreading to the vertebral column and an actinomycotic epidural granuloma was causing medullary compression. After decompression by laminectomy and antibiotic treatment with penicillin there was some neurological improvement. The condition is rare, and some of the diagnostic difficulties are discussed. PMID- 2601990 TI - Neuroblastoma in an adult causing spinal cord compression: report of a case and review of the literature. AB - Adult neuroblastoma (ANB) is an uncommon malignancy, there being only 42 reported cases in the world literature. The purpose of this report is to present a case of ANB with spinal cord compression by an intraspinal component, and review methods of diagnosis and treatment. NB is one of the most frequent childhood malignancies (90% of the patients are less than 10 years old) and both pathologists and clinicians tend to exclude it from differential diagnosis when the patient is an adult. When the tumour is located in the paraspinal region, local extension through the intervertebral foramen into the spinal canal can occur in a dumbbell fashion, a pattern of growth first described by Weber in 1856. PMID- 2601991 TI - Acute spinal cord compression in hereditary multiple exostoses: case report. AB - A case of hereditary multiple exostoses with spinal cord compression by a costal exostosis is reported in a 12-year-old boy. Paraplegia is an unusual complication of hereditary multiple exostoses. In the patient with spinal cord signs, the offending exostoses should be defined with appropriate roentgenograms and myelographic and CT scanning investigations. PMID- 2601992 TI - Mycotic thoracic aortic aneurysm producing vertebral body destruction and paraplegia: case report. AB - In the surgical treatment of an aortic aneurysm, disruption of the blood supply to the spinal cord, resulting in paraplegia and anaesthesia below the level of involvement, is a dreaded complication. Occasionally, when an aortic aneurysm compresses a major vessel that supplies the anterior spinal artery, spinal cord ischaemia and paraplegia can occur before surgery. In the case presented here, however, preoperative paraplegia appears to have resulted from direct spinal destruction by an infected aortic aneurysm that was originally diagnosed as a spinal abscess. The patient underwent operative repair, but her aorta was so friable that the sutures would not hold. Despite repeat surgery, her condition rapidly proved fatal. This case shows that, in patients with a suspected spinal abscess, computer tomographic scanning and angiography should be performed to confirm the diagnosis and to rule out other pathological conditions. An accurate pre-operative diagnosis will permit adequate operative planning and prevent catastrophic results. PMID- 2601993 TI - Water sports injuries. AB - Water sports can be a great source of fun and fitness but can also be a source of injury. Overuse injuries are common in both the recreational and competitive athlete and in the young and old alike. Proper attention to preseason conditioning, adequate warmup, early recognition and treatment of injuries, and a common sense approach to the athletic environment should minimize time off from sports and result in maximum enjoyment and performance. PMID- 2601994 TI - Discharge planning and home health care: what every staff nurse should know. AB - Recent changes in government regulations and hospital reimbursement practices have increased the importance of early, effective discharge planning. This article summarizes the goals of discharge planning, identifies the members of the interdisciplinary team and their roles in the process, and describes the staff nurse's role. PMID- 2601995 TI - Emergency nursing management of the multiple trauma patient. AB - This case study reinforces key principles in caring for multiply injured trauma victims. The Primary Survey is a tool developed to allow those caring for trauma patients to prioritize injuries. Those injuries identified in the Primary Survey will be the most life threatening. PMID- 2601996 TI - Fluid resuscitation in the adult trauma patient. AB - Successful fluid resuscitation of the trauma patient requires prompt assessment and initiation of fluid therapy. This article discusses the fluids and blood components that may be used in the resuscitation period for the adult trauma patient, as well as potential complications of fluid resuscitation therapy and nursing interventions. PMID- 2601997 TI - Neurologic assessment of the multiple trauma patient. AB - Assessment and documentation of neurologic deficits are critical for prompt intervention to correct or prevent the deficit. The ability to identify signs and symptoms of neurologic deficit which may be life threatening or permanently disabling is an important component of nursing assessment for multiple trauma patients. PMID- 2601998 TI - Interpreting your patient's oxygenation status. AB - Interpretation and comparison of arterial blood gases and oximetry readings provide data quickly about a patient's oxygenation status. Factors that alter normal values or interfere with accuracy of readings must be considered. The nurse can use this information to assess the patient's respiratory needs and make appropriate changes in the plan of care. PMID- 2601999 TI - Disseminated intravascular coagulation: a nursing challenge. AB - Altered clotting encompasses a wide spectrum of clinical conditions ranging from bleeding disorders to abnormal clot formation. DIC is an abnormal overstimulation of the normal coagulation process resulting from several clinical conditions that illustrate these extremes. In orthopaedic patients, DIC can develop following trauma (crush injuries), tissue necrosis, fat embolism, gram-negative or gram positive sepsis, and venous stasis (bedrest). Because of its occurrence as a secondary process and its subtle development, DIC can elude early recognition, diagnosis, and treatment. PMID- 2602000 TI - Blood samples for alcohol and drug screens. PMID- 2602001 TI - Calcified cerebral sinus thrombosis in infancy--CT appearances with pathological correlation. AB - A case of calcified cerebral venous sinus thrombosis in an infant is described, with autopsy correlation. Calcification of sinus thrombosis is rare. A triangular calcific density was demonstrated in the superior sagittal sinus, with extension of linear calcification laterally into the transverse sinuses. Following intravenous contrast administration there was intense enhancement of the superior sagittal and transverse sinuses around the calcified thrombus. The cerebral hemispheres showed generalised atrophy. Autopsy confirmed a calcified venous sinus thrombus. Triangular calcium density within the sagittal sinus or linear calcification within the transverse sinuses would appear to be characteristic of calcified cerebral sinus thrombus. PMID- 2602002 TI - Unusual brain MRI findings in a patient with hypomelanosis of Ito. AB - We present a patient of Hypomelanosis of Ito who had an extensive and unusual lesion in centrum semiovale of the left cerebral hemisphere shown by MRI of the brain with only minimal abnormality of the CT of the brain. PMID- 2602003 TI - Posterior mediastinal cystic teratoma surrounded by fat in a 13 month old boy. Value of magnetic resonance imaging. AB - A 13 month old boy had a large left sided posterior cystic mass initially thought to be in lung. MRI showed the cystic mass to be surrounded by fat. A benign mediastinal teratoma was removed. PMID- 2602004 TI - 4-S neuroblastoma on high field MR. AB - The appearance of 4-S neuroblastoma imaged with high field strength MR are reported. The correlative pathological findings are described. PMID- 2602005 TI - The sternoclavicular joint in trauma: retrosternal dislocation versus epiphyseal fracture. PMID- 2602006 TI - Hypertrophic osteoarthropathy caused by lung metastasis of an osteosarcoma. AB - A case of hypertrophic osteoarthropathy (HOA) caused by lung metastasis of an osteosarcoma in a 14-year-old boy and the remission of the HOA after intra arterial chemotherapy is presented. The clinical, radiological and scintigraphic findings are discussed. PMID- 2602007 TI - Chondrodysplasia, type Schmid. PMID- 2602008 TI - Hirschsprungs disease, Ondine's curse, and neuroblastoma--manifestations of neurocristopathy. PMID- 2602009 TI - Schizencephaly and septo-optic dysplasia: separate entities. PMID- 2602010 TI - Computed tomographic (CT) scans in cerebral palsy (CP). AB - The CT findings in 120 cerebral palsied children are analysed. The 72.5% positive findings are correlated with the clinical types, as well as the aetiological basis for the cerebral palsy. The spastic type, 83.3% of the total number of children, had the highest positive findings. The yield was increased in children with seizures (91.3%) and those in the postnatal group (90%), as well as those with birth trauma and neonatal asphyxia (94%). The findings were those of atrophy in 30.8%, hydrocephalus, in 10%, infarct in 11.6%, porencephaly in 8.3% and others. The atropic changes and their patterns are explained. Treatable lesions, such as tumour, hydrocephalus, subdural haematoma, porencephaly and hygroma were identified in 22.5% of cases. It is concluded that CT scan is definitely efficacious in the management of cerebral palsied children. PMID- 2602011 TI - Lung disease in the very immature neonate: radiographic and microscopic correlation. AB - Radiographic-pathologic correlation of pulmonary patterns has not been performed in very small preterm infants below 28 weeks of gestation. The radiologic findings of linear interstitial densities or generalized airspace opacity coincided with histologic changes of edema and hemorrhage and indicate that this is the most frequent abnormality producing radiographic pulmonary opacification in infants of 23-27 weeks gestation. On occasion, parenchymal immaturity alone results in lung opacification, reflecting the established interpretation of diffuse atelecatasis as the histologic-radiographic finding in respiratory distress syndrome. PMID- 2602012 TI - Pulmonary sequestration and related congenital disorders. A clinico-radiological review of 41 cases. AB - Forty-one children with pulmonary sequestration complex were reviewed. This disease is a spectrum of disorders involving the bronchopulmonary airway, the arterial supply to the lungs, the lung parenchyma and its venous drainage. The review showed pulmonary sequestration to be ubiquitous in its presentation: "classical" features of sequestration occurred in 20 (49%) children studied. The early diagnosis of children with sequestration outside infancy demands a high index of suspicion by the radiologist. The role of angiography in demonstrating an anomalous systemic arterial supply to the lung in suspected bronchial and pulmonary arterial sequestration is described in relation to alternative imaging techniques available. PMID- 2602013 TI - Potential of early chest roentgen examination in ventilator treated newborn infants to predict future lung function and disease. AB - The potentially of early chest X-ray to predict the risk of lung function abnormalities was studied prospectively in 40 preterm ventilator treated infants in a 8-10-year follow-up investigation. According to the findings at chest X-ray 3 to 10 days after completed ventilator treatment the infants were divided into 3 groups considered to represent increasing risk and severity of lung damage: 1) normal findings, 2) interstitial parenchymal abnormalities exclusively or 3) in combination with local or general hyperinflation. Lung function tests and chest x ray were performed at the age of 8 to 10 years. A correlation was found between the findings at the early chest roentgen examination and the risk of abnormal lung function at the follow-up. Occurrence of focal or general hyperinflation or both were associated with a greater risk of airway obstruction. Infants with only interstitial abnormalities were, however, at a higher risk than those with normal chest examination to develop general hyperinflation and increased air way obstruction. PMID- 2602014 TI - Pneumomediastinum caused by foreign body aspiration in children. AB - In a retrospective review of 155 children with tracheobronchial foreign body aspiration (FBA), there were ten patients who had pneumomediastinum (PM) on an initial chest radiograph. Nine of ten presented with PM and one patient had PM noted after bronchoscopy. In a child less than two years of age with no history of trauma, the radiographic finding of PM should prompt further investigation for FBA. PMID- 2602015 TI - Chest x-ray findings in the acute phase of Kawasaki disease. AB - We reviewed the chest x-ray (CXR) findings and clinical courses of 129 patients with Kawasaki disease and found abnormal CXR findings in 14.7% of the patients. Reticulogranular pattern was the most frequent abnormality (89.5%), while peribronchial cuffing (21.1%), pleural effusion (15.8%), atelectasis (10.5%) and air trapping (5.3%) were also seen. In each of these patients, CXR abnormalities appeared within 10 days after the onset of illness. In the group with abnormal CXR findings, a statistically significant increase was noted in duration of fever, incidence of adventitious sounds, serum CRP levels and incidence of coronary arterial lesions and pericardial effusion, as compared with the group having normal CXR findings. The pathological basis of these CXR changes is not clear, since no biopsy or autopsy specimen was obtained from these patients, none of these patients showed definite heart failure, it is difficult to consider that abnormal CXR findings were due to heart failure. On the other hand, physical signs and previous pathological reports suggested that the causes of abnormal CXR findings were lower respiratory tract inflammation and/or pulmonary arteritis. PMID- 2602016 TI - MRI of surgically created pulmonary artery narrowing in the dog. AB - Narrowing of the pulmonary arteries was created surgically in twelve dogs. In six of the dogs the narrowing was central (main pulmonary artery), and in the remaining six the narrowing was located peripherally at the hilar level of the right pulmonary artery beyond the pericardial reflection. MRI and angiography were performed in all dogs. MRI clearly delineated the site of the pulmonary band and the caliber of the pulmonary artery at the site of the band in all dogs (N = 6). MRI was not able to visualize any of the stenosis of the right pulmonary arteries at the hila, beyond the pericardial reflection. In addition, optimal imaging planes to depict each segment of the central pulmonary arteries were determined. The capability to image in oblique planes is essential in evaluating the morphology of the central pulmonary arteries. PMID- 2602017 TI - Intussusception: clinical and radiographic factors influencing reducibility. AB - Hydrostatic reduction of intussusception by barium or air enema has been widely accepted. The five-year experience with this procedure at two children's hospitals is reviewed and the results compared to previous studies. Various clinical and radiographic factors are evaluated in relation to the reduction rate. The findings show that the more distal the intussusception is encountered, the lower the rate of reduction. However, 25% are reduced within the rectum with no evidence of increased complications. Small bowel obstruction and prolonged duration of signs and symptoms decreased the rate of reduction statistically but there is no significant increase in complication rate in those attempted, contrary to a previous report. The cresent sign (dissection sign) and age of the patient are not significant factors in reduction as reported by other studies. PMID- 2602018 TI - Evaluation of potential practical oral contrast agents for pediatric magnetic resonance imaging. Preliminary observations. AB - Development of a practical oral contrast agent for magnetic resonance imaging is necessary to improve differentiation of bowel from adjacent structures. In order to find a readily available, inexpensive, non-toxic, palatable solution for use in the pediatric population, several formulas, milk products and a common oral sedative were evaluated in vitro. T1, T2 and signal intensity measurements were performed on a 1.5 T system. Similac with standard iron proved to be a useful high signal intensity agent on multiple pulse sequences. Early in vivo experience in four normal volunteers indicates that this agent provides excellent delineation of the stomach and duodenum from contiguous viscera. Distal small bowel visualization is less predictable. Further clinical trials should confirm the utility of this solution, which contains a combination of iron salts and paramagnetic metallic ions. PMID- 2602019 TI - Magnetic resonance imaging in children with acute hip pain. AB - 45 children presenting with acute hip pain were prospectively evaluated with conventional radiography, radioisotope bone scan, and magnetic resonance imaging (MRI). The final diagnoses were transient synovitis (n = 17), septic arthritis (n = 2), Legg-Calve-Perthes disease (LCPD, n = 13), epiphyseal dysplasia (n = 2), other conditions (n = 4), and normal findings (n = 7). In the work-up MRI provided more morphologic information than other techniques and enlarged the diagnostic possibilities. It was the only imaging technique able to give an early indication of bone marrow involvement in systemic diseases. For the early diagnosis of LCPD, MRI was as sensitive as isotope bone scan and more precise than conventional radiography. In the follow-up of LCPD patients MRI was not able to indicate the start of revascularisation of the necrotic area, which bone scans showed reliably in six patients: but MRI provided excellent evaluation of the position, form and size of the femoral head and the surrounding soft tissues. PMID- 2602020 TI - Comparison of radiolabeled monoclonal antibody and magnetic resonance imaging in the detection of metastatic neuroblastoma in bone marrow: preliminary results. AB - Magnetic resonance imaging (MRI) was compared with iodine-131-labeled monoclonal antibody scanning for ability to detect bone marrow metastases in the spine, pelvis, and femurs of children with disseminated neuroblastoma. The five patients in this study had received high-dose chemotherapy and radiation, either with (N = 2) or without (N = 3) bone marrow transplants. MRI disclosed marrow abnormalities at all sites detected with the radiolabeled antibody, which is highly specific for neuroblastoma. However, several diffuse and multifocal marrow changes apparent on MR scans were not present on scintigrams, indicating that MRI is probably less specific than monoclonal antibody imaging. Both methods were more useful than conventional radiography, computed tomography, and 99mTc-MDP bone scans for identifying sites of marrow involvement by neuroblastoma. PMID- 2602021 TI - Physeal involvement in chronic recurrent multifocal osteomyelitis. AB - Chronic recurrent multifocal osteomyelitis is a recently recognized disease characterized by remissions and exacerbations of multiple bone lesions which radiographically and pathologically have the appearance of hematogenous osteomyelitis. No consistent etiology can be identified, and antimicrobial agents seem to have no beneficial effect. A review of the appearances on imaging modalities and the clinical and pathologic manifestations is undertaken in seven cases of CRMO. No therapeutic regimen resulted in consistent clinical or radiographic improvement. We suggest the sequelae of this process are not as benign as previously reported. PMID- 2602022 TI - Neonatal mucolipidosis 2. The spontaneous evolution of early bone lesions and the effect of vitamin D treatment. Report of two cases. AB - Evolution of the early bone lesions in two children with mucolipidosis 2 was followed from birth. The progression of the bone changes did not differ from healing of rickets. Low levels of 1,25-(OH)2-D3 were found in one child and he was treated with vitamin D; resolution of the rachitic changes was more rapid than in the untreated child. It is suggested that in mucolipidosis 2 bone reacts to two independent factors, one controlling calcium metabolism, the other depending on the primary lysosomal enzyme defect. Since ricket-like features are not present in the other mucolipidoses or mucopolysaccharidoses, the defect of calcium metabolism seems to be related to the specific enzyme defect of mucolipidosis 2. PMID- 2602023 TI - Low dose imaging of scoliosis: use of a computed radiographic imaging system. AB - A digital radiographic system using the technology of laser stimulated luminescence has been utilized for the evaluation of scoliosis at reduced exposure levels. A total of 412 examinations have been performed on children with scoliosis. Diagnostic images were produced at significantly reduced radiation exposures when compared to standard radiographic techniques. Exposure reductions of 92% to 95% were consistently achieved. Since the potential for multiple examinations and considerable radiation exposure in this patient population is high, this is a significant application in the developing technology of digital radiography. PMID- 2602024 TI - Tillaux fractures of the tibia (in adolescents). AB - The juvenile "Tillaux" fracture occurs in a specific age group and may be misinterpreted as a simple sprain if proper examination is not performed. Anatomic reduction is necessary to prevent long term damage to the ankle joint. Computed tomography is of help in the evaluation of adequacy of reduction. PMID- 2602025 TI - Acampomelic campomelic dysplasia. AB - Two newborn infants with respiratory distress showed all the clinical and radiologic stigmata of the campomelic dysplasia except campomelia itself. PMID- 2602026 TI - Axillary artery aneurysm in a patient with tuberous sclerosis. PMID- 2602027 TI - Spontaneous liver adenoma in a child. PMID- 2602028 TI - An unusual anterior chest wall tumor due to actinomycosis in a child. PMID- 2602029 TI - Ossifying metastasis in lymph nodes and other bones in osteosarcoma. PMID- 2602030 TI - Cardiac function, substrate utilization, and myocardial energy metabolism studied with 31-P NMR spectroscopy during acute hypoglycemia and hyperketonemia. AB - Whether severe hypoglycemia alone or in combination with hyperketonemia might cause deterioration of cardiac function has been controversial. Therefore, the influence of acute hypoglycemia (mean 33 mg/dL) with and without hyperketonemia (mean 1.3 and 3.3 mM) on cardiac function, substrate utilization, and myocardial high energy phosphate levels was studied in 10 mongrel dogs. After 45 min of hypoglycemia, mean aortic pressure, total peripheral resistance, and myocardial oxygen consumption had increased significantly, but other hemodynamic parameters and regional myocardial function had not changed. Additional infusion of 3 hydroxybutyrate did not affect hemodynamic variables significantly. During both metabolic interventions in vivo phosphorus-31 nuclear magnetic resonance spectroscopy showed stable levels of myocardial phosphocreatinine, ATP, as well as the phosphocreatinine/ATP (3.0-3.2) ratio. Biochemical measurements revealed that hyperketonemia led to significant alterations in arterial concentrations and arteriocoronary venous differences of selected citric acid cycle intermediates, thus confirming previous reports which suggested a blockade of the 2-oxoglutarate dehydrogenase reaction induced by ketone body oxidation. However, despite this blockade, the energy supply to the heart was not impaired as shown by normal nuclear magnetic resonance spectroscopy and cardiac performance. It is speculated, that the blockade might be due to an enhanced NADH/NAD ratio. PMID- 2602031 TI - Developmental changes in the electrophysiologic properties of rabbit papillary muscles. AB - We studied the electrophysiological properties of adult (AD) and newborn (NB) rabbit papillary muscles in vitro with superfusion of normal Tyrode's solution, solutions with elevated [K+]o, and in solutions with various concentrations of tetrodotoxin. In control solutions, the NB papillary muscles had a more negative resting membrane potential (-83.6 +/- 1.2 versus -80.0 +/- 1.5 mV), a higher rate of rise of phase 0 (134 +/- 5 versus 120 +/- 5 V/S) and a higher, longer-lasting action potential plateau than the AD papillary muscles. Exposure to elevated [K+]o led to a significant post-repolarization refractoriness in AD papillary muscles that was more than that for NB papillary muscles even when NB papillary muscles were depolarized to the same resting membrane potential as the AD papillary muscles. The NB papillary muscles were comparatively resistant to tetrodotoxin in terms of percent reduction of conduction velocity and percent rise in the current threshold for excitation. The conduction velocity for AD papillary muscles in control solution (66 +/- 6 cm/s) was more than for NB papillary muscles (44 +/- 4 cm/s), which would not be expected from the data on the rate of rise of the action potential, suggesting that the cable properties of NB papillary muscles (specifically a greater surface to volume ratio of the ventricular cells) are also significantly different from the AD papillary muscles. PMID- 2602032 TI - Central hemodynamic and regional blood flow changes in the newborn with right ventricular hypertension. AB - To evaluate the central hemodynamic and regional blood flow changes associated with right ventricular hypertension in the newborn, 13 anesthetized, mechanically ventilated piglets less than 3 d old were acutely instrumented to permit measurements of central vascular pressures, cardiac output, and regional blood flow (radio-labeled microsphere technique). After initial measurements, right ventricular afterload was progressively increased by means of a pulmonary arterial mechanical occluder until right-to-left foramen ovale shunt was observed. An increase in pulmonary arterial pressure from 32 +/- 2 to 55 +/- 3 mm Hg was associated with a decrease in PaO2 from 364 +/- 16 to 88 +/- 9 mm Hg and an increase in the shunt fraction from 13 +/- 1 to 28 +/- 1% (p less than 0.01) during ventilation with oxygen. Right ventricular hypertension induced a significant decrease in systemic arterial pressure from 79 +/- 3 to 63 +/- 4 mm Hg, and left ventricular cardiac output from 156 +/- 10 to 112 +/- 11 mL.min-1.kg 1 (p less than 0.01), likely secondary to a reduction in left ventricular compliance. Oxygen delivery to the brain and heart were unaffected, due to a substantial increase in regional blood flow, but a significant reduction in delivery to the bowel and kidneys were observed. Contrary to what has been reported in the adult, myocardial blood flow to the right ventricle increased during hypertension. Metabolic acidosis was seen in all animals and the changes in serum bicarbonate and whole body oxygen consumption were directly related to the magnitude of decline in systemic O2 delivery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602034 TI - Blood flow during cardiopulmonary resuscitation with simultaneous compression and ventilation in infant pigs. AB - We determined whether the simultaneous chest compression and ventilation (SCV) technique of cardiopulmonary resuscitation (CPR) enhances cerebral (CBF) and myocardial (MBF) blood flows and cerebral O2 uptake in an infant swine model of CPR as it does in most adult animal CPR models. We also tested whether SCV-CPR sustains CBF and MBF for prolonged periods of CPR when these flows ordinarily deteriorate. CPR was performed in two groups (n = 8) of pentobarbital anesthetized piglets (3.5-5.5 kg) with continuous epinephrine infusion (10 micrograms/kg/min). Conventional CPR was performed at 100 compressions/min, 60% duty cycle, 1:5 breath to compression ratio and 25-30 mm Hg peak airway pressure. SCV-CPR was performed at 60 compressions/min, 60% duty cycle and 60 mm Hg peak airway pressure applied during each chest compression. Peak right atrial and aortic pressures in excess of 80 mm Hg were generated during CPR in both groups. At 5 min of conventional and SCV-CPR, MBF was 38 +/- 7 and 46 +/- 7 mL.min-1.100 g-1 (+/- SE), respectively, and CBF was 15 +/- 3 and 13 +/- 2 mL.min1. 100 g-1, respectively. However, as CPR was prolonged to 50 min, the sternum progressively lost its recoil and the chest became more deformed. Lung inflation at high airway pressure with SCV-CPR did not prevent this chest deformation. Aortic pressure gradually declined, whereas right atrial and intracranial pressure remained constant in both groups. Consequently, MBF and CBF fell less than 10 mL.min-1.100 g-1 and cerebral O2 uptake was markedly impaired during prolonged conventional and SCV-CPR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602033 TI - Effects of prenatal dexamethasone or terbutaline exposure on development of neural and intrinsic control of heart rate. AB - This study compares the effects of prenatal exposure to terbutaline (a beta adrenergic agonist) and dexamethasone (a glucocorticoid) on the development of heart rate control mechanisms in the rat. Both drugs produced a persistent reduction in resting heart rate appearing during the 2nd postnatal wk, but by different mechanisms. Terbutaline affected the development of autonomic input from the CNS, characterized by a premature shift from sympathetic to parasympathetic dominance; thus, heart rate differences between terbutaline exposed animals and controls resolved with acute treatment with a ganglionic blocking agent (chlorisondamine). Dexamethasone did not alter neural input to the myocardium (its actions were not reversed by ganglionic blockade), but instead reduced the intrinsic heart rate; the prenatal glucocorticoid treatment also reduced the sensitivity of the myocardium to beta-adrenergic stimulation, a factor that could contribute to the alterations in intrinsic rate. These results suggest the potential need for studies of the functional cardiovascular consequences of fetal or neonatal therapeutic interventions with glucocorticoids or adrenergic agents. PMID- 2602035 TI - Treatment of patent ductus arteriosus after exogenous surfactant in baboons with hyaline membrane disease. AB - The effect of early treatment of patent ductus arteriosus (PDA) on the acute course of hyaline membrane disease was tested in a primate model, after intratracheal administration of 100 mg/kg exogenous bovine surfactant phospholipids at mean ages between 2.3-2.4 h. Twenty-two premature baboons were divided into four groups: seven animals were controls (group A); five were treated with surfactant but PDA was not intervened (group B); in five surfactant treatment was followed by three doses of 0.2 mg/kg intravenous indomethacin beginning at a mean age of 5.5 h (group C); and in five surfactant treatment was followed by a surgical ligation of PDA between 5-5.5 h of age. After surfactant instillation in groups B, C, and D, a prompt and sustained improvement was noted in a/APO2, mean airway pressure, ventilator efficiency index and pulmonary compliance. However, no consistent differences were found in the respiratory variables within the surfactant treated groups during the 72-h experiment: the respiratory course in the animals treated for PDA (groups C and D) was generally similar to the animals in which PDA was not treated (group B). In animals treated with surfactant and indomethacin (group C) the mean aortic blood pressure was maintained more optimally as compared to the other three groups. These findings suggest that although a significant early ductal shunting does occur after exogenous surfactant therapy in this animal model, the expected pulmonary deterioration does not occur, and an early abrupt interruption of PDA does not seem to provide additional advantage to the immediate course of hyaline membrane disease. PMID- 2602036 TI - Effect of patent ductus arteriosus on water accumulation and protein permeability in the lungs of mechanically ventilated premature lambs. AB - To examine the effect of a patent ductus arteriosus on water accumulation and protein permeability in the premature, ventilated lung, we studied 16 lambs at 121-127 d gestation (term = 145 d). Water accumulation was assessed by the wet:dry wt ratio of the blood-free left lung. Protein permeability was assessed by the albumin content and by the recovery of 125I-albumin in the right lung lavage fluid 1 h after intravenous injection. Using a model that allows mechanical control of ductus patency, we compared nine lambs with patent ductus (left-to-right shunts 42 +/- 18% to left ventricular output) with seven lambs with closed ductus. The animals were studied over 3 h. In the open ductus lambs, 0.85 +/- 0.36 and 1.76 +/- 1.87%/h of the injected 125I-albumin was recovered in the lavage fluid and lung tissue, respectively. In the closed ductus lambs, the corresponding amounts were 0.71 +/- 0.21 and 0.71 +/- 0.22%/h; these differences were not statistically significant. Similarly, blood-free wet:dry ratios did not differ significantly between the two groups (7.01 +/- 1.28 open ductus versus 6.55 +/- 0.82 closed ductus). We concluded that patency of the ductus arteriosus does not significantly affect water accumulation and net protein transudation into the airways of preterm lambs in the first hours of life. Therefore, some other feature of immaturity must be responsible for the large protein leaks previously observed by others. PMID- 2602037 TI - Altered brainstem sensory processing as assessed by reflex modification procedures in infants at risk for apnea. AB - Reflex modification procedures were used to test sensory processing in premature infants to examine the relationship between respiratory abnormalities and brainstem neuronal function. A total of 73 premature infants at risk for apnea and/or infants receiving methylxanthine therapy was given a 12-h pneumocardiogram and reflex modification test at a comparable postconceptional age, before discharge. Reflex modification was tested using a controlled eyeblink-eliciting tap to the glabella presented either alone or with a 1 kHz 90-dB SPL tone. The amplitude of the glabellar tap eyeblink and acoustically modified blink were lower in infants discharged on cardiac/apnea monitors (n = 36) than in the unmonitored group (1.44 and 1.59 volts versus 2.15 and 2.39 V, p less than 0.005, respectively). At follow-up, 12 monitored infants had clinically significant apnea after discharge. The records of this subgroup of infants revealed a significantly lower augmentation of the glabellar eyeblink response when compared to all infants screened for respiratory abnormalities and to the other monitored babies (p less than 0.01). The data suggest that abnormalities of the ventilatory pattern and occurrence of clinical apnea in preterm infants may in some measure be related to acoustic sensory processing, implying an alteration of brainstem neuronal function and organization. PMID- 2602038 TI - Genioglossus and diaphragm activity during obstructive apnea and airway occlusion in infants. AB - To document mechanisms contributing to upper airway collapse, we compared the electromyographic activity of the genioglossus (GG) and diaphragm (DIA) during spontaneous mixed and obstructive apnea and during induced end-expiratory airway occlusion in 11 premature infants. In addition to ventilation and esophageal pressure measurements, we obtained DIA and GG electromyograms (EMG) from subcostal and sublingual surface electrodes, respectively. Amplitude of the DIA EMG and the frequency of occurrence of the GG EMG were determined for: 1) the breath preceding apnea or occlusion, 2) the initial and last obstructed inspiratory efforts, and 3) the first breath at resolution of both apnea and occlusion. During spontaneous apnea with airway obstruction amplitude of the DIA, EMG decreased on the initial obstructed inspiratory effort and did not exceed that of the breath preceding apnea until reestablishment of flow. In contrast, during end-expiratory airway occlusion, the amplitude of the DIA EMG increased both during and at release of occlusion. In 18 +/- 6% of the spontaneous apneic episodes, GG EMG was present with the breath preceding apnea and this frequency did not increase significantly until resolution of the apnea. During induced airway occlusion, GG EMG was not present with the breath preceding occlusion but its frequency did increase to 58 +/- 8 and 42 +/- 8% with the last occluded inspiratory effort and the first breath after release of occlusion, respectively. The decreased presence of the GG EMG from the last occluded effort to the breath at release of occlusion (58 +/- 8 versus 42 +/- 8%, p less than 0.05) was probably due to the greater mechanoreceptor-mediated inhibition associated with reestablishment of flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602039 TI - Cerebral artery flow velocity acceleration and deceleration characteristics in newborn infants. AB - To evaluate maturational differences in the cerebral artery blood flow velocity characteristics, we measured the middle cerebral (MCA) and basilar artery blood flow velocity and time intervals using a real-time imaging pulsed Doppler system in 39 preterm and 25 term infants. Preterm MCA and basilar artery mean Doppler spectral area under the curve were approximately 22 and 25% lower than the corresponding term values, with a significant increase during gestation as revealed by regression models. Paradoxically, the mean MCA systolic acceleration and deceleration slopes were approximately 28 and 18% higher in preterm than in term infants: acceleration 701.2 +/- 160 cm/s2 versus 546.4 +/- 156.5/s2 (p less than 0.005), and deceleration 222.2 +/- 71.6 cm/s2 versus 188.2 +/- 52.2 cm/s2 (p less than 0.05), respectively. Similarly, acceleration and deceleration pressure half times for MCA were about 15 and 18% shorter in the preterm (p less than 0.01 and less than 0.005). Multiple regression models controlling for velocity and frequency terms revealed an inverse relationship between gestational age and MCA acceleration (p less than 0.005), and a positive relationship between gestational age and MCA acceleration pressure half times (p less than 0.02). In preterm infants the MCA specific index of pulsatility was about 32% higher (p less than 0.05) than in the term, which was also inversely related to gestational age in a regression model controlling for velocity terms (p less than 0.02). However, the basilar artery acceleration and deceleration slopes were not significantly different between term and preterm groups, nor showed a significant gestational age effect in the multiple regression models.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602040 TI - Cases of neuroblastoma missed by the mass screening programs. AB - Twenty-two reported cases of neuroblastoma missed by the mass screening programs were reviewed (six cases in Sapporo City where a quantitative measurement for both vanillylmandelic acid (VMA) and homovanillic acid (HVA) is used and 16 cases in the districts of qualitative judgment only for VMA), and some potential factors for missing a patient were discussed. Most of the 22 patients were diagnosed over 12 mo and had advanced clinical stages at diagnosis (III or IV). Of the 17 cases whose outcome in prognosis was available, nine cases were dead and only three cases were alive without any trace of tumor. Fluctuation in the amounts of urinary VMA and HVA seemed to be one of the causes for missing a patient, especially with a small tumor. The comparison about tumor wt, VMA and HVA amounts, and clinical stage between the 22 true positive cases in Sapporo City and 46 ones in the districts of qualitative methods, and the difference in detection rate between the two groups suggested that the qualitative methods missed more patients with a small tumor. The patients who had abnormally high amounts of HVA with low amounts of VMA accounted for a fairly large part of the missed cases in Sapporo City as well as in the districts of qualitative methods. To the contrary, no patient of this type was found even among the 22 true positive cases in Sapporo City. PMID- 2602041 TI - Altered growth and protein turnover in rats fed sodium-deficient diets. AB - The effects of feeding a sodium-deficient (NaD) diet were examined in young, growing rats. All animals were fed the same diet and drank distilled water. In the control group the water contained 37 mM sodium chloride. After 2-3 wk body composition measurements were performed and epitrochlearis muscle protein synthesis and degradation rates determined. The experimental group gained only 45% of the wt and 70% of the length seen in the control group. The difference in wt gain could not be accounted for by differences in extracellular volume which averaged only 4% of body wt. Although total food intake was equivalent in both groups, urinary ammonia plus urea nitrogen excretion was higher in the experimental animals. Protein synthesis, measured as the incorporation of 14C phenylalanine into muscle protein was significantly lower in NaD rats (56.58 versus 68.79) and (65.26 versus 83.88 nmol phenylalanine/h/g wet wt (both p less than 0.01) when incubated with or without the addition of insulin (1 mU/mL). Net protein degradation rates were unchanged. Gastrocnemius muscle RNA concentrations were also lower in NaD rats (1.09 versus 1.52 mg/g wet wt, p less than 0.001). There were no changes noted in the concentration of protein within either gastrocnemius or epitrochlearis muscles. These results suggest that in rats, the growth failure seen in sodium deficiency: 1) affects both length and wt gain; 2) is not associated with decreased nutrient intake; 3) is due to decreased rates of muscle protein synthesis without affecting net protein degradation rates; and 4) is associated with diminished muscle tissue RNA concentrations. PMID- 2602042 TI - Interaction of human lactoferrin with DNA: one-step purification by affinity chromatography on single-stranded DNA-agarose. AB - Human lactoferrin has been purified to apparent homogeneity with high recovery (greater than 95%) in one chromatographic step using immobilized single-stranded DNA-agarose. Human colostral whey, at neutral pH, was loaded onto columns of DNA agarose; a single purified protein, lactoferrin, was eluted using elevated ionic strength buffers. The lactoferrin purified in this manner was shown to be homogeneous by high-performance ion-exchange chromatography (Mono-S), immobilized metal ion (Cu2+) affinity chromatography, and reverse-phase (C18) chromatography. Electrophoresis on SDS-polyacrylamide gradient (10-20%) gels and silver staining showed the purified lactoferrin preparation to contain a single protein of 78 kD with intact immunologic determinants. Similar results were obtained before and after iron saturation of the colostral whey proteins. Apolactoferrin purified in this manner was shown to bind iron with high affinity. These results demonstrate the effectiveness of immobilized DNA as one of the most rapid and complete lactoferrin purification procedures described thus far. PMID- 2602043 TI - Determination of the production and metabolic clearance rates of 1,25 dihydroxyvitamin D3 in the pregnant sheep and its chronically catheterized fetus by primed infusion technique. AB - Because little is known regarding the determinants of plasma 1,25 dihydroxyvitamin D3(1,25(OH)2D3), or its fate in the fetus, we used a primed infusion technique, using physiologic amounts of high specific activity 3H 1,25(OH)2D3 to study the in vivo production rate (PR) and metabolic clearance rate (MCR) of 1,25(OH)2D3 in chronically catheterized maternal and fetal sheep during the last month of gestation (term = 145 d). The fetal MCR of 1,25(OH)2D3 was calculated at steady state, achieved within 2 h, and was found to be 2.53 +/- 0.19 mL/min (mean +/- SEM) compared to the maternal value of 15.9 +/- 0.94 mL/min. When expressed on a body wt basis, the fetal MCR of 1.22 +/- 0.09 mL/min/kg was more than 4-fold higher than the corresponding maternal value of 0.27 +/- 0.02 mL/min/kg. Measurement of endogenous plasma 1,25(OH)2D3 by RIA revealed mean fetal values of 89 +/- 10 pg/mL compared to the maternal value of 65 +/- 9 pg/mL. Fetal daily PR of 0.33 +/- 0.024 micrograms/d was 22% of the maternal PR of 1.49 +/- 0.11 micrograms/d. However, calculation of PR on a body wt basis revealed a fetal value of 0.159 +/- 0.012 micrograms/d/kg that was more than 6-fold higher than the maternal value of 0.025 +/- 0.002 micrograms/d/kg. Thus, fetal plasma concentrations of 1,25(OH)2D3 are sustained in the face of a high clearance rate of the hormone. The high MCR may be related to the high in vivo circulating concentrations of 1,25(OH)2D3, fetal to maternal placental transfer or target tissue uptake. In view of the high turnover of 1,25(OH)2D3, we suggest that this hormone has a biologic importance that warrants further investigation. PMID- 2602044 TI - Postmortem time and storage temperature affect the concentrations of hypoxanthine, other purines, pyrimidines, and nucleosides in avian and porcine vitreous humor. AB - An HPLC method was used to determine whether postmortem time and storage temperature affect the concentrations of purines, pyrimidines, and nucleosides in avian and porcine vitreous humor. Inosine, hypoxanthine, xanthine, uric acid, uracil, uridine, and thymine were identified in the vitreous humor of chickens (Gallus domesticus). Time from death to sample collection (0-192 h) influenced the concentrations of all seven compounds (p less than 0.01 to less than 0.0001). The storage temperature of chicken carcasses before sampling (6 or 20 degrees C) had a significant influence on the concentrations of inosine, hypoxanthine, xanthine, uric acid, uracil, and thymine (p less than 0.05 to less than 0.0001). The interaction of postmortem time with temperature was significant for all seven compounds (p less than 0.01), with the rate of increase in concentration over time being higher at 20 than 6 degrees C. At 0 h postmortem, the vitreous humor of pigs (Sus scrofa) contained detectable levels of hypoxanthine, uracil, and uridine. Inosine, hypoxanthine, xanthine, guanosine, guanine, uracil, and uridine were detected after storage of pig eyes for 24 h at 20 degrees C. Between 0 and 24 h postmortem, there was a 22-fold increase in hypoxanthine concentration and a 13-fold increase in uracil concentration (p less than 0.0001). It was concluded that postmortem time and temperature are factors that must be taken into consideration when making comparisons of purines, pyrimidines, and nucleosides between groups and in relating postmortem vitreous humor hypoxanthine concentrations to antemortem hypoxia. PMID- 2602045 TI - [The effect of 6-month provocation with gluten on the height and weight of children with celiac disease]. AB - Gluten challenge was performed in 22 coeliac children in the period of histological remission. Gluten in dose 0.5 g/kg was administered for 6 months. Before the Provocation Test over 60% of children have had body weight over 50 c for normal children in Warsaw. Standardized mean body weight (+ 0.13 +/- 1.1) and height (+ 0.04 +/- 1.05) of the investigated coeliac children did not differ significantly from the values of normal Warsaw population (p greater than 0.005). A 6 month provocation with gluten leading to the histological relapse did not affect body weight and height of tested children; over 50% have had body weight and height over 50 c. Mean standardized body weight (- 0.002 +/- 1.0) and height height (-0.07 +/- 0.91) did not differ significantly from the normal values (p greater than 0.05) and corresponding values before the provocation (p greater than 0.05). It seems that Provocation Test with gluten carried out in the above way does not inhibit physical development of children with coeliac disease. PMID- 2602046 TI - [Evaluation of the effect of gluten-free diet on nutritional status of children with florid celiac disease]. AB - A dynamics of Nutritional Status of 55 children with recently diagnosed coeliac disease was assessed during the treatment with gluten free diet. No deterioration of the nutritional status was seen in 34.1% of the investigated children (time 0) whereas different degree of nutritional deficiency was noted in the remaining 75.9% of children including 10% of children with severe deficiency. After a 2 year therapy with gluten-free diet a deteriorated nutritional status was only found in 8.6% of children. In 27 children with gluten free diet for nearly 3 years, with maintenance of histological remission, the percentage of children with nutritional deficiency was 7.2%. The fact of normal Nutritional Status in more than 30% of the investigated coeliac children at the time of the initial diagnosis seems to be an effect of early and proper initial diagnosis. PMID- 2602047 TI - [Acute renal failure in neonates and infants]. AB - Causes, course and prognosis in 90 cases of the acute renal failure in neonates and infants have been discussed. All cases were treated between 1971 and 1985. Recently, an increase in the incidence of the acute renal failure is being noted. The acute diarrhoea and hemolytico-uremic syndromes are the most frequent cause of the acute renal failure. Consequences of the acute renal failure and its complications require further nephrological care. PMID- 2602048 TI - [Results of immunotherapy with HDM (Bencard) in children with bronchial asthma]. AB - Desensitization with HDM manufactured by Bencard was carried out in a group of 20 children with bronchial asthma showing hypersensitivity to Dermatophagoides pteronyssimus allergen in prick skin tests. Ten randomly selected children treated symptomatically and with climate served as a control group. Children were examined clinically before and after desensitization. Clinical improvement was observed 15 months after desensitization together with weakened delayed bronchial response to allergen inhalation. No significant difference in patency of airway was seen in both groups. Differences in serum IgE and IgG levels and mean eosinophilia in the peripheral blood were statistically insignificant. PMID- 2602049 TI - [Long term results of surgical treatment of biliary atresia]. PMID- 2602050 TI - [Wiskott-Aldrich syndrome in an infant with a family history of ulcerative colitis]. PMID- 2602051 TI - [A case of Coffin's and Lowry's syndrome]. PMID- 2602052 TI - [Etiology of the Hallerman-Streif syndrome]. PMID- 2602053 TI - [Heterotopy of colonic mucous membrane in the navel skin of a 1.5 year old child]. PMID- 2602054 TI - [Infantile hemangioendothelioma in a 10-week old girl]. PMID- 2602055 TI - [Free amino acids in umbilical cord blood in chronic intrauterine fetal hypoxia]. PMID- 2602056 TI - [Long term results of the development of children delivered by cesarean section]. PMID- 2602057 TI - [Therapeutic and immunomodulating effects of T-activin in frequently ailing children with acute pneumonia]. PMID- 2602058 TI - [Several social and genetic risk factors in the development of bronchial asthma and asthmatic bronchitis in children]. PMID- 2602059 TI - [Clinical and epidemiological characteristics of primary pyelonephritis in children and adolescents]. PMID- 2602060 TI - [Parameters of cellular adaptation in newborn infants in health and in perinatal injuries of the CNS]. AB - A study was made of the level of compensatory and adaptive reactions in red blood cells (intensity of membranous metabolism, lipid peroxidation, malonic dialdehyde (MDA) metabolism, changes in the correlation of lipid fractions) in the newborn in health and in perinatal CNS injuries within the first days of life. Changes in the indicated parameters were examined after preincubation of red blood cells under physiologic conditions and by means of MDA addition to the incubation medium. It is concluded that the newborn with perinatal CNS injuries are marked by metabolic inertness and reduced cellular adaptation in red blood cells preincubated under physiologic conditions as well as by pronounced disadaptation under the conditions of excess MDA. PMID- 2602061 TI - [Contents of bioelements in blood of newborn infants with a history of chronic intrauterine hypoxia]. AB - Emission analysis with the use of induced plasma was employed to measure the content of 9 bioelements (potassium, sodium, calcium, magnesium, phosphorus, iron, copper, zinc and selenium) in the blood serum of 82 neonates with a history of chronic intrauterine hypoxia and in 19 normal children at birth and in the course of early adaptation. It has been shown that the content of bioelements in the blood of normal neonates was marked by a number of characteristic features reflecting to a considerable degree the processes of metabolic adaptation of the children to the intrauterine life. The neonates with a history of hypoxia demonstrated the unbalance of bioelements most pronounced by day 3 of life. The treatment instituted did not make the content of bioelements in the neonates' blood return to normal. PMID- 2602062 TI - [Functional mechanisms of the adaptation of the cardiovascular system in premature children]. AB - Uni-dimensional echocardiography was used to determine cardiac output in 84 conventionally normal premature infants aged 7-30 days. The children aged 7-15 days demonstrated a direct relationship between the stroke and minute volumes of the heart and body weight. However, such a relationship was not discovered in infants aged 16-30 days. It has been established that with age there was an increase both in the absolute and relative magnitudes of the stroke and minute volumes of the heart (calculated per unit of the weight and surface of the body). The time-course of changes in the cardiac output in premature infants during the first month of life is one of the mechanisms of cardiovascular system adaptation, aimed at the creation of more favourable conditions for body supply with oxygen. PMID- 2602063 TI - [Adaptation of the cardiac activity in healthy newborn infants during the first 5 days after birth according to the hours of life]. AB - It has been revealed for the first time that adaptation of cardiac activity in normal neonates of the first five days of life is wavy in nature. At the same time the load of the right heart reduced during the first 12 hours and from 42 to 60 hours and increased from 15 to 39 hours and from 63 to 72 hours of the children's life. As a result of the establishment of the pulmonary circulation, the load of the right heart appreciably declined on day five after birth as compared with the first hour of the neonates' life. PMID- 2602064 TI - [Clinical-instrumental diagnosis of myocardial diseases in the newborn infants and their treatment]. AB - The authors provide the results of clinico-instrumental examinations of 120 neonates with myocardial pathology. Depending on the data obtained the clinical injuries to the myocardium were distributed into congenital myocarditis, hypertrophic cardiomyopathies and posthypoxic cardiopathies. Criteria for their diagnosis and treatment are described. The results of the follow-up studies of these children aged 6 months and 1 year are provided. PMID- 2602065 TI - [Circulating immune complexes and neutrophil function in low-birth-weight newborn infants in the early neonatal period]. AB - Peripheral blood neutrophil function and the content of circulating immune complexes in funic blood were examined in 35 premature neonates with low body weight, 27 neonates with grade I prematurity and in 24 normal full-term neonates (a control group) by days 1-2 and days 7-8 of life. The positive time-course of changes in the neutrophil capacity for completed phagocytosis and in the content of circulating immune complexes was disclosed in full-term neonates with low body weight at birth. The same parameters showed a negative time-course of changes in premature neonates. PMID- 2602066 TI - [Blood anticoagulation system and urine fibrinolysis in newborn infants with suppurative-inflammatory diseases]. AB - The anticoagulative blood system, blood and urine fibrinolysis were studied in 95 children with pyo-inflammatory diseases (PID) and in 56 normal neonates aged 2 to 28 days. The patients afflicted with PID were distributed into 3 groups; group I included patients with uneventful localized PID, group II consisted of patients with grave PID, and group III of patients with sepsis. Hemostasis and urine fibrinolysis were compared according to 20 indicators. The intensity and involvement of certain components of the fibrinolytic and anticoagulative blood systems in PID turned out different and were dependent on the disease gravity. PMID- 2602067 TI - [Current problems of the activities of ambulatory-polyclinical establishments in child health care]. PMID- 2602068 TI - [Intradermal hormonal test in girls with disorders of sex development]. PMID- 2602069 TI - [Kinetics of gentamycin in the treatment of newborn infants with infectious inflammatory diseases]. PMID- 2602070 TI - [Renal response to lasix infusion therapy in newborn infants]. PMID- 2602071 TI - [Chlamydia pneumonia and bronchitis in children]. PMID- 2602072 TI - [Determination of left and right handedness of children during the 1st year of life]. PMID- 2602073 TI - [Characteristics of nutrition of pregnant and breast-feeding women]. PMID- 2602074 TI - [Phytotherapy in pediatrics]. PMID- 2602075 TI - [Concerning the article of S. S. Zhamerichev, "Disputable questions about epidemic parotitis" (Pediatriia, 1988, No. 12, p. 71-74)]. PMID- 2602076 TI - [Congenital amegakaryocytic thrombocytopenia associated with cellular immunodeficiency state]. PMID- 2602077 TI - [Apert's syndrome (acrocephalosyndactylia) in a 6-month-old child]. PMID- 2602078 TI - [A case of bilinear hybrid leukemia]. PMID- 2602079 TI - [Paragonimiasis in children]. PMID- 2602080 TI - [Hemosorption in the treatment of acute belloid poisoning in children]. PMID- 2602081 TI - [Experience with intracutaneous administration of BCG vaccine to children using a needleless injector BI-IM]. PMID- 2602082 TI - [State of the antioxidant system in premature newborn infants during early postnatal period]. AB - The main parameters of the antioxidant system--AOS (glutathione peroxidase, glutathione reductase, superoxide dismutase, ceruloplasmin, estriol, estradiol) were studied in 58 normal full-term infants and in 178 premature infants in the course of the early neonatal period. In the control group, the functioning of the AOS appeared more perfect and was characterized by phasic changes in the course of the first week of life. The premature infants demonstrated functional disorganization of both enzymatic (glutathione in particular) and hormonal components of the system of antiperoxide defence. This circumstance played a substantial part in the development of polysaturated fatty acids deficiency, which determined in turn the modification of the membrane lipid content and selective loss of cell sensitivity to neuro-humoral actions and unbalance in the system of cyclic nucleotides. PMID- 2602084 TI - Stereoscopic illusion based on the proximity principle. AB - A class of ambiguous random-dot stereograms were created that share the following interesting property: Although the binocular disparity forms a periodic 'sawtooth' waveform as a function of row number (the disparity is constant for a given row), these stimuli yield a monotonically increasing depth percept along the rows. The random-dot pattern of each row is periodic along the horizontal direction for the purpose of producing an ambiguous depth percept. It is this ambiguity that makes it possible for the periodic stimulus to give rise to a monotonic percept. This monotonic percept is substantially enhanced when the rows are shown in temporal sequence instead of all being displayed together. Experiments are reported which indicate that this illusion is due to the proximity, or pulling, effect in stereopsis. PMID- 2602083 TI - Integration of stereo and texture cues in the formation of discontinuities during three-dimensional surface interpolation. AB - A series of stereograms are presented which demonstrate that texture boundaries can strongly influence the perception of discontinuities between neighbouring three-dimensional (3-D) surfaces portrayed by means of stereo cues. In these demonstration figures, no stereo information is available in the immediate vicinity of the boundary between the two 3-D stereo surfaces because all texture in that region is removed in one eye's view. On the other hand, various forms of texture boundary information are provided in the resulting monocular region. This stimulus paradigm is used to explore the question: what influence does texture boundary information have on the nature of the perceived 3-D surface that is interpolated between two stimulus regions which carry stereo cues? It is shown that if a clear-cut texture boundary is present in the monocular region then this is used by the human visual system to fix the perceived location of 3-D crease and step surface discontinuities between the stereo regions. Collett (1985) explored this issue with a similar methodology and reported weak and unreliable assistance from monocular texture boundaries in helping shape 3-D stereo surface discontinuities. The strong and robust phenomena demonstrated here seem to rely on two main differences between the present stimuli and those of Collett. In the present stimuli, figurally continuous textures containing strong texture boundaries are used, together with a technique for minimising the complications, including binocular rivalry, that arise from the borders of the stimulus regions present in only one half of each stereogram. PMID- 2602085 TI - Geometric restitution of perspective: Bartel's method. AB - Bartel's geometric restitution of perspective is explained and illustrated by application to two well-known works of art. Applications of the methods of Bartel and others are briefly discussed. PMID- 2602086 TI - The analogy between stereo depth and brightness. AB - Apparent depth in stereograms exhibits various simultaneous-contrast and induction effects analogous to those reported in the luminance domain. This behavior suggests that stereo depth, like brightness, is reconstructed, ie recovered from higher-order spatial derivatives or differences of the original signal. The extent to which depth is analogous to brightness is examined. There are similarities in terms of contrast effects but dissimilarities in terms of the lateral inhibition effects traditionally attributed to underlying spatial differentiation operators. PMID- 2602087 TI - Adaptation of suprathreshold contrast and luminance stimuli. AB - The temporal and spatial properties of the difference in perceived contrast and brightness of two suprathreshold stimuli presented successively in different retinal locations were determined. Stimulus onset asynchrony (SOA) was varied and the perceived contrast or brightness of the first stimulus (S1) was measured as a function of SOA by matching the contrast or luminance of the second stimulus (S2) to that of S1. The two stimuli overlapped in time for 200 ms to allow the comparison to be made. The adjusted values for S2 could well be fitted with an exponential decay function of SOA. For luminance increments and decrements the time constant for this function was 253 ms; for checkerboards with checks of size 16 min square the time constant was 164 ms. The difference in perceived contrast was dependent on initial contrast in a nonlinear fashion. It increased with increasing check size and was independent of the mean luminance and spatial proximity of the two stimuli. The phenomenon was observed with different pattern types and with dichoptic presentation, but could only be seen when direct comparison of the two stimuli was possible. PMID- 2602088 TI - Figure and ground in space and time: 1. Temporal response surfaces of perceptual organization. AB - The figure-ground organization of an ambiguous bipartite pattern can be manipulated by altering the temporal-frequency content of the two regions of the pattern. Ambiguous patterns in which the two regions of each pattern contained sine-wave gratings of either 8, 4, 1, or 0.5 cycles deg-1 undergoing contrast reversal at rates of 0, 3.75, 7.5, or 15 Hz were tested for figure-ground organization under conditions of equated space-averaged and time-averaged luminance and perceived contrast. All combinations of temporal-frequency differences between the two regions were tested at each spatial frequency. The data are reported for two levels of temporal resolution (15 and 30 s). The pattern region with the relatively higher temporal frequency tended to be seen as the background a higher percentage of the viewing time. There were significant linear trends for the appearance as background of the region of higher temporal frequency with respect to the magnitude of the temporal-frequency difference between the two regions of each pattern for all spatial frequencies and data intervals except the final 15 s interval of the lowest (0.5 cycle deg-1) spatial frequency condition. PMID- 2602089 TI - Figure and ground in space and time: 2. Frequency, velocity, and perceptual organization. AB - The figure-ground organization of an ambiguous bipartite pattern in which the two regions of the pattern contained sine-wave gratings which differed in spatial frequency was examined for two pairs of spatial frequencies: 1 and 4 cycles deg 1, and 1 and 8 cycles deg-1. The region of higher spatial frequency underwent contrast reversal at one of four rates: 0, 3.75, 7.5, or 15 Hz. The region of lower spatial frequency was equated with either the temporal frequency or the velocity of the grating of higher spatial frequency in three sets of conditions: one stationary condition, three in which temporal frequency was equated, and three in which velocity was equated. For the 1 and 4 cycles deg-1 pair, the region of lower spatial frequency tended to be seen as the background a higher percentage of the time. There were significant linear trends for the appearance as background of the region of lower spatial frequency with respect to the magnitude of the velocity difference between the two regions of the pattern. The faster the 1 cycle deg-1 grating moved with respect to the 4 cycles deg-1 grating, the higher the percentage of the time it was seen as the ground. The results for the 1 and 8 cycles deg-1 pair were in some cases unexpected in that the 8 cycles deg-1 grating was seen as the ground behind the 1 cycle deg-1 grating even though it was of a higher spatial frequency and moved at a slower velocity. The spatiotemporal tuning of the visual system is discussed. PMID- 2602090 TI - Motion aftereffects and retinal motion. AB - Two experiments are described in which it was investigated whether the adaptation on which motion aftereffects (MAEs) are based is a response to retinal image motion alone or to the motion signal derived from the process which combines the image motion signal with information about eye movement (corollary discharge). In both experiments observers either fixated a stationary point or tracked a vertically moving point while a pattern (in experiment 1, a grating; in experiment 2, a random-dot pattern) drifted horizontally across the field. In the tracking condition the adapting retinal motion was oblique. In the fixation condition it was horizontal. In every case in both conditions the MAE was horizontal, in the direction opposite to that of pattern motion. These results are consistent with the hypothesis that the adaptation is a response to the motion signal derived from the comparison of eye and image motion rather than to retinal motion per se. An alternative explanation is discussed. PMID- 2602091 TI - Circular vection as a function of the relative sizes, distances, and positions of two competing visual displays. AB - In studies where it is reported that illusory self-rotation (circular vection) is induced more by peripheral displays than by central displays, eccentricity may have been confounded with perceived relative distance and area. Experiments are reported in which the direction and magnitude of vection induced by a central display in the presence of a surround display were measured. The displays varied in relative distance and area and were presented in isolation, with one moving and one stationary display, or with both moving in opposite directions. A more distant display had more influence over vection than a near display. A central display induced vection if seen in isolation or through a 'window' in a stationary surrounding display. Motion of a more distant central display weakened vection induced by a nearer surrounding display moving the other way. When the two displays had the same area their effects almost cancelled. A moving central display nearer than a textured stationary surround produced vection in the same direction as the moving stimulus. This phenomenon is termed 'contrast-motion vecton' because it is probably due to illusory motion of the surround induced by motion of the centre. Unequivocal statements about the dominance of an eccentric display over a central display cannot be made without considering the relative distances and sizes of the displays and the motion contrast between them. PMID- 2602092 TI - Infants' reactions to visual movement of the environment. AB - It has been demonstrated many times that the posture of infants is affected by movement of the visual environment. However, in previous studies, measurements taken with infants less than 10 to 12 months of age have always been recorded with the infants in a sitting position. An experiment is reported in which the postural reactions to a sinusoidal movement of the visual environment were recorded in infants 7 months of age and older standing with support. Fifty subjects divided into five groups (mean age 7.15 to 48.6 months) participated in the experiment. The groups differed in age and motor ability. Movement of the visual environment was achieved by means of a floorless room that could be moved sinusoidally in the anteroposterior axis. The subjects had to stand holding a horizontal bar fixed to a force-measurement platform. For each subject, measurements were made during four 60 s intervals: two with movement of the room and two with the room stationary. For all groups, reactions in the anteroposterior axis were stronger than in the lateral axis and this was true for both stimulus conditions. Comparison of the differences between the movement and stationary conditions in the anteroposterior axis, as a function of age, shows that the youngest infants seemed paradoxically to give stronger reactions when the room was stationary than when it was moving; the inverse was true for older infants and this difference increased with age. An analysis of the data with fast Fourier transforms reveals that the majority of subjects showed a pattern of postural reactions where the dominant (peak) frequency was identical to the peak frequency of room movement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602093 TI - Verbal transformations in the aged. AB - The susceptibility of aged persons to verbal transformations was studied in an experiment with ambiguous verbal stimuli ('reversible words'). Twenty-five subjects, aged 64 to 86 years, participated in the experiment. The results indicate that the aged are somewhat less susceptible to verbal reversals than are young adults, but there seem to be no age differences in the type of illusory forms heard. These results differ from those of experiments with nonreversible words, which show a very low rate of transformation and a total absence of transformations into meaningless forms in the aged. It is hypothesized that the reversibility of repeated ambiguous patterns is a general phenomenon arising from satiation, whereas transformations of repeated unambiguous verbal stimuli, involving phonetic distortions, are based on specific speech-perception mechanisms that are absent in the aged. PMID- 2602094 TI - Matching forces: constant errors and differential thresholds. AB - A contralateral limb-matching procedure was used to study the perception of forces generated by the elbow flexor muscles. Subjects were required to generate forces ranging from 15 to 85% of their maximum voluntary contraction (MVC range: 169-482 N), and after achieving the target force to produce a force of the same perceived intensity with their contralateral arm. Under these conditions, subjects consistently overestimated the amplitude of the two lowest forces, and the most accurate matching of forces occurred in the middle of the response range (around 50% MVC). This pattern of constant errors could be explained in terms of an artifact of the starting position, which has been shown to influence the accuracy of judgements of stimulus magnitude. The Weber fraction for force calculated from the matching data was 0.07, which is within the range reported previously for weight. These thresholds are, however, considerably lower than those described for friction and the moment of inertia, the perception of which also involves the proprioceptive system. PMID- 2602095 TI - Arrows-anchors: figure-ground reversals. PMID- 2602096 TI - [MR imaging of acute hemorrhagic brain infarction]. AB - Six patients with acute hemorrhagic brain infarct were imaged using spin-echo (SE) pulse sequences on a 1.5 Tesla MR scanner. Including two patients with repeated MR imaging, a total of eight examinations, all performed within 15 days after stroke, were analyzed retrospectively. Four patients revealed massive hemorrhages in the basal ganglia or cerebellum and three cases demonstrated multiple linear hemorrhages in the cerebral cortex. On T1-weighted images, hemorrhages were either mildly or definitely hyperintense relative to gray matter, while varied from mildly hypointense to hyperintense on T2-weighted images. T1-weighted images were superior to T2-weighted images in detection of hemorrhage. CT failed to detect hemorrhages in two of five cases: indicative of MR superiority to CT in the diagnosis of acute hemorrhagic infarcts. PMID- 2602097 TI - [MRI of middle cerebral artery occlusion]. AB - Magnetic resonance imagings (MRIs) of ten patients with angiographically proved middle cerebral artery (MCA) occlusion were retrospectively reviewed. Eight of the ten patients had cerebral infarcts, one had an intraventricular hemorrhage, and the remaining one had no significant abnormalities. All patients were examined by the 1.5 Tesla SIGNA (GE), using spin-echo pulse sequences. In all patients, occluded MCA could be detected by MRI. All occluded arteries showed absence of flow void and were demonstrated as iso- or hyperintense structures relative to gray matter on T1-weighted images, iso- or hypointense on T2-weighted images. In eight of the ten patients, absence of flow void in the sylvian fissure was observed on T2-weighted images. Thus, MRI was proved to be a pertinent diagnostic modality for evaluating MCA occlusions. PMID- 2602099 TI - [MRI of internal carotid occlusion and high-grade carotid stenosis]. AB - Magnetic resonance imaging (MRI) of twelve patients with angiographically proved internal carotid artery (ICA) occlusions and a patient with high-grade ICA stenosis was retrospectively reviewed. In one of the occluded ICA cases, the bilateral ICAs were involved. All patients were examined by a 1.5 Tesla system, using spin-echo pulse sequences. Both absence of normal flow void and decreased caliber of the cavernous portion of the ICA were detected in all patients. In ten of the thirteen occluded ICAs, flow void was completely absent. Most of the occluded arteries were isointense relative to gray matter on T1-weighted images, and were mildly hypointense on T2-weighted images. "Partial flow void" was observed in four cases, including the high-grade stenosis patient. So-called "border zone infarcts" were detected in seven patients (eight hemispheres). In three of the thirteen cases, however, cerebral infarcts relating to the ICA occlusions or high-grade stenosis were not observed. Since detection of abnormal ICA before cerebral infarct has occurred is extremely significant, we want to stress that abnormal ICA must be routinely searched for in the routine review of MRI of the head. PMID- 2602098 TI - Radiographic findings and hypotensive reactions in excretory urography. AB - The radiographic findings and the hypotension patterns were reviewed in 19 patients having hypotensive reactions in routine excretory urography using ionic contrast medium. The lowest systolic blood pressure was above 80 mmHg in 10 patients while below 80 mmHg in remaining 9 patients. The urogram was unremarkable as long as the systolic blood pressure was preserved above 80 mmHg. In 2 patients, whose systolic blood pressure decreased quickly beyond 80 mmHg immediately after injection of contrast medium, the pyelogram was faint or non visualized. On the other hand, in 4 patients, whose systolic blood pressure decreased beyond 80 mmHg in several minutes after injection of contrast medium and remained under 80 mmHg for more than 20 minutes, the nephrogram was dense and the pyelogram was faint or non-visualized. Although systolic blood pressure decreased beyond 80 mmHg, the urogram was unremarkable in 3 patients. This was due to the delayed hypotension or the short duration of hypotension. PMID- 2602100 TI - [The effects of contrast media on the cardiac conducting system in coronary angiography]. AB - Comparative study of ionic and nonionic contrast media was carried out to investigate the effects on the cardiac conducting system caused by sodium ion and osmolality in coronary angiography. We evaluated the effects on the cardiac conducting system by 5% Glucose (5% GL), 20% glucose (20% GL), saline (SL), Ioxaglate 320 (IOX, ionic low-osmolar contrast medium, ionic LOCM), Iopamidol 370 (IOP 370, non ionic low-osmolar contrast medium, nonionic LOM) and 60% Diatrizoate (DTA, high-osmolar contrast medium, HOCM). In 18 patients who underwent coronary angiography, the effects on the cardiac conducting system were investigated using P-P time, A-H time, H-V time, QTc, T-wave height from His bundle electrogram and surface electrocardiogram. Prolongations of P-P time, A-H time and QTc with 20% GL, DTA were significantly longer than with IOX, IOP 370, 5% GL, and SL (p less than 0.01). There was almost no difference among 5% GL, SL, IOX, and IOP 370 in both P-P and A-H times. Also, prolongations of QTc with IOX, IOP 370 were longer than with 5% GL and SL (p less than 0.01). H-V time was not significantly prolonged with all solutions. The change of T-wave height with IOX was significantly greater than with IOP 370 (p less than 0.01). The change of T wave height with SL was significantly greater than with 5% GL and that of T-wave height with 60% DTA was significantly greater than with 20% GL (p less than 0.01). Prolongations of P-P time, A-H time, QTc and changes of T-wave height were correlated with osmolality (p less than 0.01). These observations suggested that main factor of the disturbances of the cardiac conducting system excluding change of T-wave height was high osmolality of solution. Sodium ion took little part in the disturbances, and the factor of T-wave height change was not only due to the osmolality but also due to the concentration of sodium ion. LOCM caused much less significant disturbances of the cardiac conducting system than HOCM. There was almost no difference between non-ionic LOCM and ionic LOCM excluding the change of T-wave height. PMID- 2602101 TI - [CT evaluation of trabecular and cortical bone mineral density of the lumbar spine in patients on hemodialysis]. AB - It is difficult to evaluate the severity of bone involvement in patients on maintenance hemodialysis (HD) by the measurement of vertebral bone mineral density (BMD), since many endocrine factors influence bone metabolism, making the value of BMD variable from high to low. It is also difficult to interpret the BMD measured in one ROI (region of interest) since bone density distribution is sometimes very heterogenous. On the other hand QCT method is useful to evaluate the value of trabecular and cortical bone mineral density separately. Vertebral BMD was measured in 138 patients on maintenance HD, by using DEQCT (dual energy QCT). 161 patients without bone metabolic disorders were studied for control group. In patients on HD, various BMD values ranging from high to low were observed, and there was no correlation between BMD value and duration of HD. The number of patients with low mineral content was greater than that with high mineral content in both cortical and trabecular bone. The trabecular BMD decreased with age, and the speed of BMD decline was the same in both sexes. The rapid decrease of trabecular BMD after menopause seen in control female group was not observed in female patients on hemodialysis. The deviation of BMD from the age-matched average BMD value was smaller in older male patients than that in young male and female patients. In order to evaluate the difference of change between the trabecular and cortical bone at the same vertebra, cases in which discrepancy of Z-score was more than 0.2 were divided into three groups; group A: increased trabecular BMD (Z-score greater than 1), group B: decreased trabecular BMD (-1 greater than Z-score), group C: normal trabecular BMD (-1 less than Z score less than 1), and in each group T/C ratio (Z-score of trabecular BMD/Z score of cortical BMD ratio) was evaluated. In group A, almost all cases showed trabecular BMD to be higher than cortical, and in group B, 60% cases showed trabecular BMD to be lower than cortical, suggesting that the change of BMD in trabecular bone is greater than that in cortical bone. PMID- 2602102 TI - [Experimental study of transvascular direct current treatment for intraabdominal malignant tumors]. AB - Direct current treatment (DCT) is a treatment for malignant tumors suggested by Nordenstrom in 1978. In DCT, two platinum electrodes, an anode and a cathode, are introduced percutaneously. Usually the anode is inserted into the tumor, and the cathode is inserted into healthy tissue near the tumor. Passage of a direct current acidifies the surroundings of the anode and causes necrosis of this part of the tumor. DCT has been used to treat lung cancer and superficial tumors clinically, but it has not yet been used for intra-abdominal tumors. Here, basic and experimental studies were made of the possibility of DCT of intra-abdominal tumors. A modification, called transvascular DCT, was done with the anode inserted into the liver of rabbits and the cathode placed within a blood vessel by vascular catheterization. First, tests were done to identify a suitable material for the cathode, from the standpoint of safety. DCT is usually done with platinum electrodes. However, in transvascular DCT, platinum could not be used for the cathode because with its use, hydrogen gas was produced in the vessel, causing embolisms. So, a cathode made of AgCl and coated with Ag was developed to prevent embolism. With this cathode, gas was not generated. Next, pathological changes in the walls of the vessel that contained the cathode were observed after DCT. The cathode was put into a tube placed in the inferior vena cava (IVC) or the aorta. a. IVC: A histological study done immediately after DCT showed an area of necrosis in the wall of the IVC in all 19 rabbits. A study done 7 days after DCT showed damage in the IVC wall of all five animals examined. b. Aorta: A histological study done immediately after DCT showed a small edematous area in the wall of the aorta in seven of the 22 animals, and no evidence of any damage in the other 15. A study done 7 days after DCT showed no damage in any of the 16 animals. The aorta was more suitable for use as the vessel to contain the cathode than the IVC, because injury of its wall was minor and reversible. Thus, transvascular DCT could be done safely by use of an Ag-coated cathode made of AgCl and placed in the aorta. PMID- 2602103 TI - [Partial volume effect in MRI--a phantom study]. AB - According to the direction and the thickness of the imaging slice in tomography, the border between the tissues becomes unclear (partial volume effect). In the present MRI experiment, we examined border area between fat and water components using phantom in order to investigate the partial volume effect in MRI. In spin echo sequences, the intensity of the border area showed a linear relationship with composition of fat and water. Whereas, in inversion recovery and field echo sequences, we found the parameters to produce an extremely low intensity area at the border region between fat and water. This low intensity area was explained by cancellation of NMR signals from fat and water due to the difference in the direction of magnetic vectors. Clinically, partial volume effect can cause of mis evaluation of walls, small nodules, tumor capsules and the tumor invasion in the use of inversion recovery and field echo sequences. PMID- 2602104 TI - [Investigation of low-contrast signal detection in computed radiography (CR)]. AB - Threshold contrasts of low-contrast objects were compared between screen-film and computed radiography (CR) systems. Effects of incident exposure to the imaging plate (IP) and contrast enhancement on the detectability of low-contrast objects were also studied. We employed 18-alternative forced-choice (18AFC) experiments to study the dependence of the threshold contrasts of the test objects on the incident exposure, object size, and contrast enhancement. The results indicated that the threshold contrasts of CR system were comparable to that of the medium speed screen-film system and increased by decreasing x-ray exposures. Although threshold contrasts decreased by contrast enhancement, the magnitude of improvement depended on the object size and incident exposure. PMID- 2602105 TI - [Analysis of cell kinetics after irradiation by flow cytometry (II)--Evaluation of clonogenic potential of G2 block cells after irradiation by cell sorting]. AB - When the tumor cells are irradiated, the percentage of the cells in the G2 + M phase and the duration of the cell cycle arrested increase with the irradiation dose. This post irradiation growth inhibition and changes in the cell kinetics observed within 48 hours of irradiation are closely correlated. Cells in the G2 + M phase are reported to be sensitive to irradiation, but little is known about their clonogenic potential. These cells must be separated for evaluation of their clonogenic potential. In this study, the clonogenic potential of irradiated G2 phase arrested cells was examined by the flow cytometric cell sorting technique. Fluorescent Hoechst staining, which allows determination of DNA content in living cells, was used. The results of DNA assay using Hoechst 33342 agreed well with those using PI staining. The concentration of Hoechst 33342 required for the DNA assay and cell sorting is 5 micrograms at which vital staining is possible with 80% cell viability. Although the clonogenic potential of non-irradiated cells was not different between those in G1 and G2 + M phases, that of the cells arrested in the G2 + M phase after irradiation was lower than that of the cells in the G1 phase. The reduction in the clonogenic potential was more notable in the cells subjected to high dose irradiation. A greater number of cells were arrested for a longer period than the cells irradiated at a lower dose. The clonogenic potential of the cells correlated well with the duration of G2 block. PMID- 2602106 TI - [Siderotic regenerating nodules in liver cirrhosis--evaluation by gradient echo (FLASH) imaging 1.5T]. AB - In three patients with histologically proven liver cirrhosis, a large number of small, low-intensity nodule(SLIN)s was clearly seen on gradient echo(GRE) images which are sensitive to field inhomogeneity. A histological study revealed that the SLINs corresponded to the regenerating nodules, laden with iron, of liver cirrhosis. As TE was prolonged, the SLINs increased in size in all three cases and fused with each other in one of three cases on GRE images. This phenomenon suggests that the magnetic susceptibility effect due to iron included in the regenerating nodules is the cause for the regenerating nodules shown as SLINs on GRE images, and that one SLIN does not always correspond to one regenerating nodule. We conclude that GRE images should be considered important for diagnosis of regenerating nodules in liver cirrhosis. PMID- 2602107 TI - [Experimental study of arterial damage induced by anti-cancer drug infusion]. AB - In order to clarify the cause of arterial changes after intra-arterial infusion of anti-cancer drugs (AI-AD) experiments were made on the arteries of rabbits. Histopathologic sections, 7 days after AI-AD revealed endothelial damage characterized by pyknosis, hyalinization with edematous change of the intimal layer. Proliferation of the endothelial cells was also observed. The cause of narrowing or occlusion of the arteries was considered to occur with thrombus formation surrounded by the proliferated endothelial cells and this suggested that thrombolytic agents would be effective to prevent these arterial changes. PMID- 2602109 TI - AIDS survey results show need for education. PMID- 2602108 TI - [Treatment with expandable metallic stent for arterial occlusive disease]. AB - Gianturco expandable metallic stents were used in 4 cases with ASO of the iliac artery after PTA for the purpose of the prevention of restenosis. The insertion of stent was succeeded in all 4 cases, and the improvement of clinical symptoms and elevation of ankle pressure index were observed. Follow-up over 3 to 8 months revealed no occlusion and migration of stent. Expandable metallic stent was suggested to be contributable to the treatment of arterial occlusive disease. PMID- 2602110 TI - Rutgers-UMDNJ joint master's program track urged by BHE. PMID- 2602111 TI - Rural nursing in an urban state. PMID- 2602112 TI - Crosslinking of transcription factor TFIIIA to ribosomal 5S RNA from X. laevis by trans-diamminedichloroplatinum (II). AB - Trans-diamminnedichloroplatinum (II) was used to induce reversible crosslinks between 5S rRNA and TFIIIA within the 7S RNP particle from X. laevis immature oocyte. The crosslinked fragments have been unambiguously identified. These fragments exclusively arise from three RNA regions centered around the hinge region at the junction of the three helical domains. Major crosslinking sites are located in region 9-21 (comprising loops A and helix II) and region 54-71 (comprising loop B, helices II and V). A minor site is also found in the 3' part of helix I and helix V (region 100-120). Our results point to the crucial role of the junction region and of the three-dimensional folding of the RNA in the recognition of the 5S rRNA by TFIIIA. PMID- 2602113 TI - Laser-induced crosslinking of histones to DNA in chromatin and core particles: implications in studying histone-DNA interactions. AB - UV laser irradiation has been used to covalently crosslink histones to DNA in nuclei, chromatin and core particles and the presence of the different histone species in the covalently linked material was detected immunochemically. When nuclei were irradiated and then trypsinized to cleave the N- and C- terminal histone tails, no histones have been found covalently linked to DNA. This finding shows that UV laser-induced crosslinking of histones to DNA is accomplished via the non-structured domains only. This unexpected way of crosslinking operated in chromatin, H1-depleted chromatin and core particles, i.e. independently of the chromatin structure. The efficiency of crosslinking, however, showed such a dependence: whilst the yield of crosslinks was similar in total and H1-depleted chromatin, in core particles the efficiency was 3-4 times lower for H2A, H2B and H4 and 10-12 times lower for H3. The decreased crosslinking efficiency, especially dramatic in the case of H3, is attributed to a reduced number of binding sites, and, respectively, is considered as a direct evidence for interaction of nonstructured tails of core histones with linker DNA. PMID- 2602114 TI - Nucleotide sequence and proposed secondary structure of Columnea latent viroid: a natural mosaic of viroid sequences. AB - The Columnea latent viroid (CLV) occurs latently in certain Columnea erythrophae plants grown commercially. In potato and tomato, CLV causes potato spindle tuber viroid (PSTV)-like symptoms. Its nucleotide sequence and proposed secondary structure reveal that CLV consists of a single-stranded circular RNA of 370 nucleotides which can assume a rod-like structure with extensive base-pairing characteristic of all known viroids. The electrophoretic mobility of circular CLV under nondenaturing conditions suggests a potential tertiary structure. CLV contains extensive sequence homologies to the PSTV group of viroids but contains a central conserved region identical to that of hop stunt viroid (HSV). CLV also shares some biological properties with each of the two types of viroids. Most probably, CLV is the result of intracellular RNA recombination between an HSV type and one or more PSTV-type viroids replicating in the same plant. PMID- 2602115 TI - Nucleotide sequence of a cDNA for phi, a histone to protamine transition protein from sea cucumber spermatozoa. PMID- 2602116 TI - Sequence of the mouse liver glucose transporter. PMID- 2602117 TI - Nucleotide sequence of a gene that encodes resistance to ethidium bromide from a transferable plasmid in Staphylococcus aureus. PMID- 2602118 TI - Nucleotide sequence of a pea U2 snRNA gene. PMID- 2602119 TI - Complementary nucleotide sequence for monitor peptide, a novel cholecystokinin releasing peptide in the rat. PMID- 2602120 TI - Nucleotide sequence of a cDNA clone representing a third allele of human protein B23. PMID- 2602121 TI - The complete nucleotide sequence of plum pox virus RNA (strain D). PMID- 2602122 TI - Sequence of the ribosomal protein gene KD4 from Schizosaccharomyces pombe. PMID- 2602123 TI - Full length cDNA sequence of porcine secreted phosphoprotein-I (SPP-I, osteopontin). PMID- 2602124 TI - A highly repeated sequence in the domestic pig: a gender-neutral probe. PMID- 2602125 TI - Nucleotide sequence of Brugia pahangi 17.4 kD protein. PMID- 2602126 TI - Nucleotide sequence of the glyceraldehyde-3-phosphate dehydrogenase gene from Thermus aquaticus YT1. PMID- 2602127 TI - The sequence of the chloroplast 5S ribosomal RNA gene of soybean (Glycine max Merr.). PMID- 2602128 TI - Nucleotide and deduced amino acid sequence of the RpoN sigma-factor of Pseudomonas putida. PMID- 2602129 TI - Nucleotide sequence of the tuf gene from Mycoplasma gallisepticum. PMID- 2602130 TI - Nucleotide sequence of the tuf gene from Mycoplasma genitalium. PMID- 2602131 TI - Polymorphic simple GATA/GACA repeats in plant genomes. PMID- 2602132 TI - Quantitative comparison of mRNA levels in mammalian tissues: 28S ribosomal RNA level as an accurate internal control. PMID- 2602133 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2602134 TI - The Caenorhabditis elegans genome contains monomorphic minisatellites and simple sequences. AB - Many species have been shown to contain tandemly repeated short sequence DNA known as minisatellites and simple sequence motifs. Due to allelic variation in the copy number of the repeat unit these loci are usually highly polymorphic. Here we demonstrate the presence of sequences in the genome of the nematode Caenorhabditis elegans which are homologous to two sets of short sequence DNA. However, when two independent strains were compared no polymorphism for these sequences could be detected. PMID- 2602135 TI - Strong structural effect of the position of a single acetylaminofluorene adduct within a mutation hot spot. AB - The NarI restriction enzyme recognition site, G1G2CG3CC, has been identified as a hotspot for -2 frameshift mutations induced by N-2-acetylaminofluorene (AAF) on the basis of a forward mutation assay in plasmid pBR322 in the bacterium Escherichia coli. AAF binds primarily to the C-8 position of guanine residues, and the three guanines of the NarI site are similarly reactive. Despite this similar chemical reactivity, only binding of AAF to the G3 residue causes the -2 frameshift mutations. To study the mechanisms underlying the specificity of the mutagenic processing further, we monitored the structural changes induced by a single AAF adduct within the NarI site by means of CD spectroscopy and thermal denaturation. The NarI sequence was studied as part of the 12-mer ACCGGCGCCACA. The purification and characterization of the three isomers having a single AAF adduct covalently bound to one of the three guanines of this 12 mer are described. The analysis of the melting profiles of the duplexes formed when these three isomers are annealed with the oligonucleotide of complementary sequence shows the same destabilizing effect of the AAF adduct on the three DNA helices. It is also shown, from the CD spectra, that modification of guanine G1 or G2 by AAF does not induce major changes in the helical structure of DNA. On the other hand, modification of guanine G3 induces a change in the CD signal that suggests the formation of a local left handed structure within the 12-mer duplex. These results show the polymorphic nature of the DNA structure in the vicinity of an AAF adduct. PMID- 2602136 TI - Large inverted duplications in amplified DNA of mammalian cells form hairpins in vitro upon DNA extraction but not in vivo. AB - I have analysed the duplex-to-hairpin transition of large inverted duplications with a short asymmetric center which are found in the amplified DNA of two mammalian cell lines resistant to cytotoxic drugs. Psoralen crosslinking experiments establish that this transition does not occur in vivo, but takes place in a significant portion of the palindromes during genomic DNA purification, at the phenol-chloroform extraction step. The introduction of single strand nicks in the DNA by gamma irradiation prior to its purification does not prevent hairpin formation but instead facilitates it. These results show that the rate-limiting step of the duplex-to-hairpin transition does not require negative supercoiling, and that transient melting of large segments of cellular DNA occurs during phenol-chloroform extraction. I also show, and discuss the fact, that only cellular DNA, and not cloned palindromic DNA, is able to undergo hairpin formation by this mechanism. These results bear practical implications for the study of inverted repeated DNA sequences in eukaryotic cells. PMID- 2602137 TI - Control of partial digestion combining the enzymes dam methylase and MboI. AB - A method is described which allows the preparation of reproducible partial digests without previous establishment of the incubation conditions. It is based on a combined application of dam methylase and the restriction endonuclease MboI, both recognizing the sequence 5'-GATC-3' but MboI unable to cut the methylated site. Due to their competition for the same substrate the DNA is partially digested, with the size of the resulting fragments strongly dependent on the ratio of enzymes. The Km of the dam methylase was determined to be 115 ng DNA/microliters indicating a variance in fragment sizes generated at low DNA concentrations. This effect is minimized above 150 ng/microliters. Any influence of digestion time is avoided, because the reaction runs until complete modification of all sites. The dependence on enzyme concentration and presence of agarose was checked. Knowledge of these parameters allows an accurate prediction of fragment sizes generated at different conditions. The technique was successfully used to construct libraries from different sources, in particular chromosome-specific libraries from small amounts of flow-sorted material. PMID- 2602138 TI - Incomplete primer extension during in vitro DNA amplification catalyzed by Taq polymerase; exploitation for DNA sequencing. AB - Polyacrylamide gel electrophoresis of DNA fragments obtained by the polymerase chain reaction using Taq polymerase revealed the presence of multiple fragments shorter than the expected product. These abortive extension products were observed even when analysis by agarose gel electrophoresis showed only a single band. The production of prematurely terminated fragments can be exploited for the sequencing of PCR products if phosphorothioate groups are incorporated base specifically during the reaction in the presence of two oligonucleotide primers, one of which is 5'-32P-labeled. The addition of snake venom phosphodiesterase to the reaction mixture after completion of the amplification cycles digests each fragment from the 3'-end to a phosphorothioate group so that the sequence can be read by polyacrylamide gel electrophoresis. PMID- 2602139 TI - The use of 5'-phospho-2 deoxyribocytidylylriboadenosine as a facile route to chemical aminoacylation of tRNA. AB - Methodology is described for the synthesis and chemical aminoacylation of the hybrid dinucleotide 5'-phospho-2'-deoxyribocytidylylriboadenosine (pdCpA). Ligation of aminoacylated pdCpA to a truncated amber suppressor tRNACUA (-CA) using T4 RNA ligase generates an aminoacylated suppressor tRNA which can be used for site-specific incorporation of unnatural amino acids into proteins. Both the ligation and in vitro suppression efficiencies are the same when either pCpA or pdCpA is used. The use of deoxycytidine simplifies the chemistry involved in the synthesis of the dinucleotide pCpA. In addition, these results demonstrate that ribocytidine is not required for recognition of the aminoacylated tRNA during protein synthesis. PMID- 2602140 TI - Primary structure and regulation of vegetative specific genes of Dictyostelium discoideum. AB - We have examined the expression and structure of several genes belonging to two classes of vegetative specific genes of the simple eukaryote, Dictyostelium discoideum. In amebae grown on bacteria, deactivation of all vegetative specific genes occurred at the onset of development and very little mRNA exists by 8 to 10 hours. In contrast, when cells were grown in axenic broth, the mRNA levels remained constant until a dramatic drop occurred around 10 to 12 hours. Thus, regulation of both classes of genes during the first several hours of development is dependent upon the prior growth conditions. Analysis of genomic clones has resulted in the identification of two V genes, V1 and V18, as ribosomal protein genes. Several other V genes were not found to be ribosomal protein genes, suggesting that in Dictyostelium non-ribosomal protein genes may be coordinately regulated with the ribosomal protein genes. Finally, using deletion analysis we show that the promoters of two of the V genes are composed of a constitutive positive element(s) located upstream of sequences involved in the regulated expression of these genes and within the first 545 upstream bp for V18 and 850 bp for V14. The regions involved in regulated expression were localized between -7 and -222 for V18 and -70 and -368 for V14. The sequences conferring protein synthesis sensitivity were shown to reside between -502 and -61 of the H4 promoter. PMID- 2602141 TI - The divergently transcribed genes encoding yeast ribosomal proteins L46 and S24 are activated by shared RPG-boxes. AB - Transcription of the majority of the ribosomal protein (rp) genes in yeast is activated through common cis-acting elements, designated RPG-boxes. These elements have been shown to act as specific binding sites for the protein factor TUF/RAP1/GRF1 in vitro. Two such elements occur in the intergenic region separating the divergently transcribed genes encoding L46 and S24. To investigate whether the two RPG-boxes mediate transcription activation of both the L46 and S24 gene, two experimental strategies were followed: cloning of the respective genes on multicopy vectors and construction of fusion genes. Cloning of the L46 + S24 gene including the intergenic region in a multicopy yeast vector indicated that both genes are transcriptionally active. Using constructs in which only the S24 or the L46 gene is present, with or without the intergenic region, we obtained evidence that the intergenic region is indispensable for transcription activation of either gene. To demarcate the element(s) responsible for this activation, fusions of the intergenic region in either orientation to the galK reporter gene were made. Northern analysis of the levels of hybrid mRNA demonstrated that the intergenic region can serve as an heterologous promoter when it is in the 'S24-orientation'. Surprisingly, however, when fused in the reverse orientation the intergenic region did hardly confer transcription activity on the fusion gene. Furthermore, a 274 bp FnuDII-FnuDII fragment from the intergenic region that contains the RPG-boxes, could replace the naturally occurring upstream activation site (UASrpg) of the L25 rp-gene only when inserted in the 'S24-orientation'. Removal of 15 bp from the FnuDII fragment appeared to be sufficient to obtain transcription activation in the 'L46 orientation' as well. Analysis of a construct in which the RPG-boxes were selectively deleted from the promoter region of the L46 gene indicated that the RPG-boxes are needed for efficient transcriptional activation of the L46 gene. We conclude that all promoter elements for the S24 gene are located within the intergenic region, where the RPG-boxes are the most likely UAS-elements. However, the intergenic region (including the RPG-boxes) is required but not sufficient to confer transcription activity on the L46 gene. PMID- 2602142 TI - Wheat nuclear protein HBP-1 binds to the hexameric sequence in the promoter of various plant genes. AB - HBP-1 is a sequence-specific DNA-binding protein that interacts with the hexameric sequence ACGTCA, the putative cis-acting element of the wheat histone H3 gene. Gel mobility shift and DNase I footprint analyses showed that this protein interacts with homologous sequences in the regulatory regions for the transcription of the cauliflower mosaic virus (CaMV) 35S RNA and nopaline synthase (NOS) genes, evidence that HBP-1 may bind to hexameric sequences in the regulatory regions of various genes. An HBP-1-like protein, indistinguishable from wheat HBP-1 in its the DNA-binding specificity, is present in sunflower nuclear extract, an indication that HBP-1-like DNA-binding proteins also exist in dicots. PMID- 2602143 TI - Regulation of mouse ornithine decarboxylase activity by cell growth, serum and tetradecanoyl phorbol acetate is governed primarily by sequences within the coding region of the gene. AB - To determine the genetic elements required for modulation of ornithine decarboxylase (ODC) activity in response to cell growth or treatment with serum or with tetradecanoyl phorbol acetate, ODC-deficient cells were transfected with a series of recombinant DNAs encoding mouse ODC. All of the transfected cells expressing an intact mouse ODC protein displayed regulation of ODC activity, including those expressing a construct deprived of all ODC-specific sequence information except the protein-coding region. ODC mRNA changed much less than enzymatic activity. A mutation of the protein-coding region that converted ODC from an unstable to a stable intracellular protein attenuated the regulatory response. We conclude that post-transcriptional events associated with ODC degradation dominate the response to these stimuli. PMID- 2602144 TI - The XLR sequence family: dispersion on the X and Y chromosomes of a large set of closely related sequences, most of which are pseudogenes. AB - The XLR sequence family encodes RNA transcripts specific to late-stage T and B cells and their neoplasms. Only one apparently functional mRNA has been identified thus far and this encodes a novel 25 kDa nuclear protein. In this report, we find that the XLR gene family is composed of 50-75 copies per haploid genome which localize to at least two different portions of the mouse X chromosome. Neither of these locations are near the xid mutation that earlier work had correlated with XLR. In addition, some members of this family are also on the Y chromosome. Another surprising finding is that while the fourteen genomic clones examined to date have the same exon-intron structure and are closely related with respect to sequence conservation (90%), all appear (in most cases by multiple criteria) to be non-functional, raising the possibility that all but one of the members of this large semi-dispersed family are pseudogenes. PMID- 2602145 TI - Cis-acting sequences from mouse rDNA promote plasmid DNA amplification and persistence in mouse cells: implication of HMG-I in their function. AB - Searching for amplification promoting sequences within the murine rDNA cistrons, we isolated two elements from the nontranscribed spacer region. These 370 bp and 423 bp long cis-acting elements, referred to as muNTS1 and muNTS2, are localized 4.1 kb and 4.6 kb upstream the RNA polymerase I transcriptional start site. They contain ca. 50 bp long AT-rich sequences that strongly interact with a protein from nuclear extracts. The protein could be purified and identified as HMG-I. A synthetic oligonucleotide encompassing the AT-rich stretch from muNTS1 is able to substitute for the muNTS elements. A similar sequence from the nontranscribed spacer of rat has previously been reported to be important for the function of the RNA polymerase I enhancer (1). Therefore the interaction of HMG I with the muNTS elements may play a role both in the stimulation of DNA amplification and transcription. PMID- 2602146 TI - Thermodynamics of the interactions of m-AMSA and o-AMSA with nucleic acids: influence of ionic strength and DNA base composition. AB - The equilibrium binding of the antitumor agent m-AMSA and its biologically inactive analog o-AMSA to native and synthetic DNAs are compared over a wide range of ionic strengths and temperatures. Although o-AMSA binds DNA with a higher affinity than m-AMSA it is not effective as an antitumor agent. Both m AMSA and o-AMSA bind DNA in an intercalative manner. Indepth investigations into the thermodynamic parameters of these interactions reveal the interaction of m AMSA with DNA to be an enthalpy driven process. In contrast, the structurally similar but biologically inactive o-AMSA binds DNA through an entropy driven process. The differences in thermodynamic mechanisms of binding between the two isomers reveal that the electronic and/or steric factors resulting from the position of the methoxy substituent group on the anilino ring directs the DNA binding properties of these compounds and ultimately the biological effectiveness as an antitumor agent. PMID- 2602147 TI - Immunoassays for carbodiimide modified DNA-detection of unpairing transitions in supercoiled ColE1 DNA. AB - The water soluble reagent N-cyclohexyl-N'-beta-(4-methylmorpholinium) ethyl carbodiimide-p-toluene sulphonate (CMC) can be used to probe for unpaired and mismatched sites in DNA. Polyclonal antibodies for CMC modified DNA were produced in order to develop immunological assays for the localization and quantitation of CMC adducts. Immunoslot blot analysis of modified DNA exhibited antibody binding proportional to the extent of CMC modification with adduct detection in the femtamole range. Unmodified DNA did not cross react under the conditions of the assay. The distribution of CMC reactivity for supercoiled ColE1 DNA modified at 100, 200 and 300 mM NaCl was determined by immunoanalysis of EcoRI-Hae2-NruI restriction fragments Southern transferred to nylon membranes. Reactivity above random expectation occurred in the A2-II fragment which can be accounted for by its high A-T content of 71.3%. Reactivity below random expectation occurred in the C fragment which can be accounted for by its low AT content of 43%. CMC modification for the other restriction fragments appeared random. PMID- 2602148 TI - The complete sequence of soybean chlorotic mottle virus DNA and the identification of a novel promoter. AB - The complete nucleotide sequence of an infectious clone of soybean chlorotic mottle virus (SoyCMV) DNA was determined and compared with those of three other caulimoviruses, cauliflower mosaic virus (CaMV), carnation etched ring virus and figwort mosaic virus. The double-stranded DNA genome of SoyCMV (8,175 bp) contained nine open reading frames (ORFs) and one large intergenic region. The primer binding sites, gene organization and size of ORFs were similar to those of the other caulimoviruses, except for ORF I, which was split into ORF Ia and Ib. The amino acid sequences deduced from each ORF showed only short, highly homologous regions in several of the corresponding ORFs of the three other caulimoviruses. A promoter fragment of 378 bp in SoyCMV ORF III showed a strong expression activity, comparable to that of the CaMV 35S promoter, in tobacco mesophyll protoplasts as determined by a beta-glucuronidase assay using electrotransfection. The fragment contained CAAT and TATA boxes but no transcriptional enhancer signal as reported for the CaMV 35S promoter. Instead, it had sequences homologous to a part of the translational enhancer signal reported for the 5'-leader sequence of tobacco mosaic virus RNA. PMID- 2602149 TI - Synthesis and evaluation of some novel phosphate and phosphinate derivatives of araA. Studies on the mechanism of action of phosphate triesters. AB - A number of novel phosphinate and phosphate triester derivatives of the anti viral nucleoside analogue araA have been prepared. Spectroscopic and analytical data have been collected on both the reagents and the nucleotides. An in vitro assay indicated inhibition of DNA synthesis by mammalian cells, by each of the nucleotide derivatives, in the range 3-30 microM. Inhibition was reduced, but not abolished, for the phosphinates relative to the phosphates. These results are consistent with a mode of action involving release of the free nucleoside araA and the nucleotide araAMP. PMID- 2602150 TI - Replication of tomato golden mosaic virus DNA B in transgenic plants expressing open reading frames (ORFs) of DNA A: requirement of ORF AL2 for production of single-stranded DNA. AB - Tomato golden mosaic geminivirus has a genome of two single-stranded (ss) DNA components, A and B. An almost identical 'common' region in DNA A and DNA B is thought to contain sequence elements controlling replication and transcription. Hence investigation of sequences important for DNA replication by in vitro mutagenesis is complicated by possible effects on the transcription of genes for replication proteins. To overcome this problem, transgenic plants expressing open reading frames (ORFs) of DNA A from an enhanced cauliflower mosaic virus 35S RNA promoter were constructed and tested for their ability to support the replication of DNA B and DNA B mutants. The results show that plants transgenic for ORF AL1 are able to support the replication of the double-stranded (ds) forms of DNA B, but that ORF AL2 is required in addition to produce ssDNA B. ORFs AL3, BL1 or BR1 were not required for replication of ds or ssDNA B. To the best of our knowledge this is the first time that essential replication proteins of a geminivirus have been expressed constitutively from a plant genome without giving rise to replicating DNA A molecules, thereby allowing DNA B to replicate alone. Such transgenic plants should enable not only the mutational analysis of sequence elements within the replication origin region, but also the construction of a new generation of vectors for gene amplification in plants, based on a minimal virus replicon. PMID- 2602151 TI - Tandem direct duplications of mitochondrial DNA in mitochondrial myopathy: analysis of nucleotide sequence and tissue distribution. AB - Two patients with direct tandem duplications of mitochondrial DNA (mtDNA) and mitochondrial myopathy are described. The breakpoint regions between duplicated segments were amplified using the polymerase chain reaction (PCR), cloned and sequenced. The distribution of normal and abnormal genomes in different tissues was investigated using Southern hybridisation, and in different cells within the same tissue using PCR. In each case the gene for cytochrome oxidase subunit I (MTCOX1) was interrupted, creating reading frames which if transcribed and translated would result in truncated versions of this peptide. Heteroplasmy and mosaicism for the abnormal mtDNA population was apparent. PMID- 2602153 TI - Synthesis, thermal stability and reactivity towards 9-aminoellipticine of double stranded oligonucleotides containing a true abasic site. AB - A 13 mers abasic oligonucleotide was synthetized. It was therefore possible to compare thermal stability and reactivity of duplex oligonucleotides either with an apurinic/apyrimidinic site or without any lesion. An important decrease in the melting temperature appeared for duplexes with an abasic site. The chemical reaction of these modified oligonucleotides with the intercalating agent 9 aminoellipticine was studied by gel electrophoresis and by fluorescence. The formation of a Schiff base between 9-aminoellipticine and abasic sites was rapid and complete with duplexes at 11 degrees C. Schiff base related fluorescence and beta-elimination cleavage were more important with the apyrimidinic sites than with the apurinic ones. When compared to previous results obtained with the model d(TprpT) some unexpected behaviours appeared with longer and duplex oligonucleotides. For instance only partial beta-elimination cleavage was observed. It is likely that stacking parameters in the double helix play a great role in the studied reaction. PMID- 2602152 TI - High resolution footprinting of EcoRI and distamycin with Rh(phi)2(bpy)3+, a new photofootprinting reagent. AB - The complex bis(phenanthrenequinone diimine)(bipyridyl)rhodium(III), Rh(phi)2(bpy)3+, cleaves DNA efficiently in a sequence-neutral fashion upon photoactivation so as to provide a novel, high resolution, chemical photofootpring reagent. Photofootprinting of two crystallographically characterized DNA-binding agents, distamycin, a small natural product which binds to DNA in the minor groove, and the endonuclease EcoRI, which binds in the major groove, gave respectively a 5-7 base pair footprint for the drug at its A6 binding site and a 10-12 base pair footprint for the enzyme centered at its recognition site (5'-GAATTC-3'). Both footprints agree closely with the crystallographic results. The photocleavage reaction can be performed using either a high intensity lamp or, conveniently, a simple transilluminator box, and the photoreaction is not inhibited by moderate concentrations of reagents which are sometimes required for examining interactions of molecules with DNA. When compared with other popular footprinting agents, the rhodium complex shows a number of distinct advantages: sequence-neutrality, high resolution, ability to footprint major as well as minor groove-binding ligands, applicability in the presence of additives such as Mg2+ or glycerol, ease of handling, and a sharply footprinted pattern. Light activated footprinting reactions furthermore offer the possibility of examining DNA-binding interactions with time resolution and within the cell. PMID- 2602154 TI - Functional domains in the bacteriophage phi 29 terminal protein for interaction with the phi 29 DNA polymerase and with DNA. AB - Deletion mutants at the amino- and carboxyl-ends of the phi 29 terminal protein, as well as internal deletion and substitution mutants, whose ability to prime the initiation of phi 29 DNA replication was affected to different extent, have been assayed for their capacity to interact with DNA or with the phi 29 DNA polymerase. One DNA binding domain at the amino end of the terminal protein has been mapped. Two regions involved in the binding to the DNA polymerase, an internal region near the amino-terminus and a carboxyl-terminal one, have been also identified. Interaction with both DNA and phi 29 DNA polymerase are required to led to the formation of terminal protein-dAMP initiation complex to start phi 29 DNA replication. PMID- 2602155 TI - Synthesis and duplex stability of oligonucleotides containing cytosine-thymine analogues. AB - The synthesis of the deoxynucleoside derived from the base P, 6H,8H-3,4-dihydro pyrimido[4,5-c] [4,5-c] [1,2]oxazin-7-one, 2, and its introduction by established phosphoramidite and H-phosphonate chemistry into oligonucleotides is described. The melting transition temperatures (Tm) of a range of heptadecamer duplexes containing P/A and P/G base-pairs are compared with corresponding ones having N4 methoxycytosine (M) 1 and mismatched normal bases. P/A and P/G pairs allow closely similar duplex stabilities and have the potential to reduce the multiplicity of probes and primers based on amino acid sequences by removing the T/C degeneracy. PMID- 2602156 TI - Nucleotide sequence of the REC1 gene of Ustilago maydis. PMID- 2602157 TI - Sequence analysis of a cDNA encoding a erabutoxin b from the sea-snake Laticauda semifasciata. PMID- 2602158 TI - Nucleotide sequence of the coat protein gene and flanking regions of Cucumber Mosaic Virus (CMV) strain I17F. PMID- 2602159 TI - Nucleotide sequence of the dog thyrotropin receptor cDNA. PMID- 2602160 TI - Nucleotide and deduced amino acid sequence of sheep serum albumin. PMID- 2602161 TI - A novel isoform of myosin alkali light chain isolated from human muscle cells. PMID- 2602162 TI - Nucleotide sequence of the Chinese hamster ornithine decarboxylase gene. PMID- 2602163 TI - DNA sequence of a small plasmid from Halobacterium strain GN101. PMID- 2602164 TI - The nucleotide sequence of a developmentally regulated cDNA from Physarum polycephalum. PMID- 2602165 TI - Nucleotide sequence of the gene encoding the RsrI methyltransferase. PMID- 2602166 TI - Sequence and putative regulatory elements in a 5S rRNA gene from a eukaryotic thermophile, Thermomyces lanuginosus. PMID- 2602167 TI - DNA sequencing with thermostable Tet DNA polymerase from Thermus thermophilus. PMID- 2602168 TI - Antithrombin III Milano 2: a single base substitution in the thrombin binding domain detected with PCR and direct genomic sequencing. PMID- 2602169 TI - Protein C London 1: recurrent mutation at Arg 169 (CGG----TGG) in the protein C gene causing thrombosis. PMID- 2602170 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2602171 TI - Prescription drug abuse in NH. PMID- 2602172 TI - Nurses should have the right to refuse to give hormone therapy to people with a mental handicap. PMID- 2602173 TI - Crossing the pain threshold. PMID- 2602174 TI - Held to account. PMID- 2602175 TI - Voluntary concerns. PMID- 2602176 TI - Brave new world. PMID- 2602177 TI - 'Caring costs'. PMID- 2602178 TI - Whose right is it, anyway? PMID- 2602179 TI - A good night's sleep. PMID- 2602181 TI - Fit for nursing--awards. PMID- 2602180 TI - Now I lay me down to sleep. PMID- 2602182 TI - Nurses' emotional labour. PMID- 2602183 TI - Assessing cardiac pain. PMID- 2602184 TI - The ups and downs of A&E. PMID- 2602185 TI - Deaf, but not disabled. PMID- 2602186 TI - Postnatal care. PMID- 2602187 TI - The Lagoon Room experience. PMID- 2602188 TI - Water: can it help childbirth? PMID- 2602189 TI - Comparison of intraosseous, intramuscular, and intravenous administration of succinylcholine. AB - The intraosseous route of vascular access has been popularized recently for resuscitation of children. Intraosseous succinylcholine use has been anecdotally reported for airway management. This drug could be utilized for control of the airway in pediatric burns, status epilepticus, or combative head-injured patients. No series quantifying the efficacy of the intraosseous route has been reported for succinylcholine. To accomplish this goal, six sheep serving as their own controls were anesthetized with halothane and subsequently intubated. Succinylcholine (1 mg/kg) was given. The time to respiratory arrest and 100% loss of the forefoot twitch upon stimulation of the anterior tibial nerve were noted. Each animal was successively studied using the intravenous (IV), intraosseous (IO), and intramuscular (IM) routes of administration, with a minimum of seven days separating trials. The average time from administration to respiratory arrest in seconds was 30.8 +/- 7.3 (IV), 57.5 +/- 10.3 (IO), and 230 +/- 106 (IM). The average time from administration to 100% loss of forefoot twitch in seconds was 93.3 +/- 34.0 (IV), 100.8 +/- 24.2 (IO), and 291 +/- 109 (IM). All groups were statistically significantly different using the t-test for the difference of means, with a p value less than 0.0015. We conclude that the intraosseous route of administration of succinylcholine in this series of sheep is comparable to the intravenous route and superior to the intramuscular route. PMID- 2602190 TI - Influence of topical anesthesia on the sedation of pediatric emergency department patients with lacerations. AB - Local anesthetic infiltration of wounds causes pain which distresses children. A painless topical anesthetic solution containing tetracaine, adrenaline, and cocaine (TAC) may reduce this distress. We hypothesized that the use of TAC for anesthesia may reduce the utilization of sedation for laceration repair. We performed a retrospective review of all pediatric emergency department (PED) patients receiving parenteral meperidine, promethazine, and chlorpromazine (DPT) during the period after TAC became routinely available. For comparison, data from a recent retrospective study of DPT (preTAC) use in the same PED were used. There was a reduction in the percent of total PED patients receiving DPT, from 1.7% preTAC to 1.2% during the TAC period (P less than 0.05). During the TAC period, there were no significant changes in patient volume or case-mix indicators. Of the major indications for DPT, there was no significant change in the percent receiving DPT for fractures, abscesses, burns, foreign body removal, or head injuries. However, there was a significant reduction in the percent of patients with lacerations receiving DPT during the experimental period, from 12% to 7.6% (P less than 0.05). There were no significant differences in laceration frequency (119/mo and 116/mo), length (2.7 and 2.7 cm), location (85% and 93% total for face and digits), or complexity (64% and 63%) for preTAC and TAC periods, respectively. We conclude that TAC used for local anesthesia may reduce the need for sedation in PED patients with lacerations that require suturing. PMID- 2602191 TI - Should patients with normal cranial CT scans following minor head injury be hospitalized for observation? AB - The purpose of this study was to determine the incidence of complications in hospitalized patients with normal cranial computed tomographic (CT) scans following minor head injury (Glasgow Coma scale of 13-15). Seventy-three patients were included in the analysis, with 63 children being assigned a GCS score of 15 at presentation. Seventy-one percent of patients were male, and motor vehicle accidents accounted for 56% of the injuries. Forty patients reported loss of consciousness (LOC) following the accident. The mean length of hospital stay was 1.69 +/- 0.94 days. GCS scores, history of LOC, vomiting, or seizures did not significantly influence length of hospitalization. None of the patients developed complications, and all were discharged in good condition. We conclude that a child with minor head injury, GCS score of 15, and a normal neurologic examination and cranial CT scan can be safely discharged to the care of a responsible adult and can be observed at home. PMID- 2602192 TI - Frequency of suspected abuse/neglect in burn patients. AB - This study was conducted to determine the frequency of suspected abuse/neglect in pediatric patients with burns presenting to an emergency department. Criteria were established for the suspicion of abuse/neglect. During a 12-month period, 431 patients were evaluated. Eighty-four (19.5%) were suspected of being abused or neglected. The frequency of suspected abuse/neglect in single-parent families was 22%, compared to 10% for married couples (P = 0.027). There was no significant difference in the rate of suspected abuse/neglect in patients seen fewer than or more than 24 hours after the injury occurred. Seventy-five children (17%) had more than two burn sites, with 24 (32%) appearing to be a result of abuse/neglect (P = 0.01). One hundred twenty-eight patients (30%) were admitted to the hospital, with 34% suspected of being abused/neglected, compared to 13% who were treated on an ambulatory basis (P = 0.00005). Fifty-eight (69%) of the suspected abused/neglected patients were diagnosed based on the history and/or physical examination. The medical records of 31% revealed previous abuse/neglect, ingestion, failure to thrive, or old burns. We conclude that abuse or neglect is a significant factor in pediatric burn patients and that the child's previous medical record must be reviewed. Other associated factors include a single parent family or the child with greater than two burn sites. The actual incidence of abuse/neglect could not be determined, owing to laws regarding confidentiality. PMID- 2602193 TI - Carbamate and organophosphate poisoning in early childhood. AB - Twenty-five infants and young children intoxicated by carbamate and organophosphorus compounds are described. Presenting signs and symptoms in children differed from those described in adults and were mainly related to severe CNS depression, coma and stupor, dyspnea, and flaccidity. Other clinical signs such as miosis, excessive salivation and tearing, sweaty, cold skin, and gastrointestinal symptoms were less frequent, while fasciculations and bradycardia were quite uncommon on arrival. Only two patients presented with all typical signs of organophosphate poisoning as described in adults. Signs of carbamate poisoning were indistinguishable from those of organophosphate poisoning and included signs of myoneural and CNS cholinergic receptor involvement, in addition to parasympathetic muscarinic dysfunction. Atropine sulfate was found to have a clear beneficial CNS effect in addition to its known peripheral antimuscarinic effect. Our data suggest that the clinical presentation of carbamate and organophosphate poisoning in early childhood and its response to therapy are quite different from those of adults and older children. PMID- 2602194 TI - A case of bilateral nursemaid's elbow. AB - Although the case presented was easily treated, it caused anguish and expense that might have been avoided had the diagnosis been entertained initially. Considering the high frequency of occurrence, radial head subluxation should be thought of in young children with upper extremity injuries, typical posturing, and no other evidence of trauma or deformity. A suggestive history should be sought, and an attempt to reduce the subluxation should be made. Parents and caretakers should be advised about the potential for recurrence of this injury, as well as the dangers of sudden traction on a child's arm. PMID- 2602195 TI - Traumatic rupture of the thoracic aorta in the pediatric patient. AB - Traumatic rupture of the thoracic aorta is rare in pediatric patients. Proper management of this injury is essential and requires a systematic approach, similar to that used in adult patients. Preoperatively, the multiply injured child must have other injuries properly prioritized and addressed. Proper selection of graft size, expeditious intraoperative management, and careful postoperative management result in a minimal number of complications associated with this injury. PMID- 2602196 TI - Severe hyperphosphatemia associated with tumor lysis in a patient with T-cell leukemia. AB - Hyperphosphatemia is an infrequent complication of the tumor lysis following induction therapy for lymphoproliferative disorders that can result in acute renal failure. We report a case of severe hyperphosphatemia resulting in transient acute renal failure corrected rapidly by hemodialysis. PMID- 2602197 TI - Treatment of severe imipramine poisoning complicated by a negative history of drug ingestion. AB - The wide use of imipramine (Tofranil) for the treatment of nocturnal enuresis continues in spite of the unique dangers associated with this drug. Young children are particularly susceptible to the potentially lethal central nervous system and cardiovascular toxicities, yet the toxic potential of imipramine remains unrecognized by both parents and too many physicians. Management of severe imipramine intoxication can be difficult. This report describes a 12-month old patient with severe imipramine intoxication whose treatment was complicated by a negative history at presentation. PMID- 2602198 TI - Ingestion of cannabis: a cause of coma in children. AB - Previous reports of accidental ingestion of cannabis by children are rare. None has reported coma, although one described a stuporous state that required assisted ventilation. Over the past four years, the staff of British Columbia's Children's Hospital has managed six children with cannabis toxicity, three of whom presented in coma, including one with airway obstruction. Recurring diagnostic features included rapid onset of drowsiness, moderate pupil dilation, hypotonia, lid lag, and the presence of small granules or leaves in the mouth. Confirmation was obtained by positive urine screening for cannabinoids. The six cases described emphasize the need for emergency physician awareness of possible diagnostic criteria, the potential severity of intoxication, and the need for prevention through parent education. PMID- 2602199 TI - Povidone iodine as a cause of factitious hematuria and abnormal urine coloration in the pediatric emergency department. AB - The observation of a cola-colored dipstick positive for "hematuria" was made in an 11-year-old black male who presented to the emergency department with a chief complaint of dysuria. Thorough questioning eventually revealed the source of these two abnormalities to be the addition of povidone iodine to the urine sample. The reported causes of abnormal urine coloration and of false positive dipstick hematuria are summarized. PMID- 2602200 TI - Corneal abrasion in infancy as a cause of inconsolable crying. AB - Inconsolable crying is a disturbing symptom in young infants. The following is a case report of an infant who presented with inconsolable crying caused by a corneal abrasion. Corneal abrasion should be considered when inconsolable crying appears in an otherwise asymptomatic infant. PMID- 2602201 TI - Accidental cocaine intoxication in a nine-month-old infant: presentation and treatment. AB - A case of a nine-month-old male who ingested cocaine is presented. The rarity of this type of ingestion, as well as the caretaker's denial of the presence of cocaine in the household, made rapid diagnosis of this infant's malady difficult. We present this case to alert physicians to the presentation and treatment of cocaine-intoxicated infants. PMID- 2602202 TI - Gaboon viper envenomation: an unexpected big-city emergency. AB - We report a pediatric case of envenomation by an extremely rare nonindigenous snake. The pathophysiology of injury is reviewed, and suggestions for appropriate treatment are given. PMID- 2602203 TI - Management strategy for penetrating oropharyngeal injury. AB - Direct force applied to an object held in the mouth may cause either superficial or penetrating injury within the oropharynx. The natural course for a majority of these injuries is spontaneous healing. Penetrating trauma in the parapharyngeal space may cause life-threatening vascular injuries. Violation of the retropharyngeal space may lead to dissecting emphysema or mediastinitis. Knowledge of these infrequent but serious sequelae complicates emergency department management decisions. PMID- 2602204 TI - Pediculosis masquerades as child abuse. AB - Pediculosis has many cutaneous manifestations. A previously unreported presentation is documented in this narrative. Maculae ceruleae associated with the head louse was initially confused with traumatic bruising and child abuse. PMID- 2602205 TI - Survival after emergency department thoracotomy in a child with blunt multisystem trauma. AB - A 14-year-old boy sustained severe blunt, multisystem trauma. On presentation, vital signs were present but disappeared despite maximal resuscitation. Emergency department thoracotomy (EDT) resulted in return of vital signs and transfer to the operating room for a definitive procedure. Ultimately, the child survived with normal neurologic function and quality of life. This case illustrates the potential value of EDT in selected patients who present with detectable vital signs and deteriorate in the face of maximal conventional therapy. PMID- 2602206 TI - Complete recovery from severe metabolic acidosis associated with isoniazid poisoning in a young boy. AB - Isoniazid (INH) poisoning is a known cause of metabolic acidosis and seizures. The following case report describes a 14-year-old boy with an INH overdose who suffered profound metabolic acidosis (pH of 6.69) and who completely recovered with no obvious sequelae. PMID- 2602207 TI - Acute asthma attack. PMID- 2602208 TI - Adolescent interpersonal assault injury admissions in an urban municipal hospital. AB - To extend the study of the epidemiology of interpersonal violence into the area of nonfatal intentional injury, a retrospective study was undertaken of patients admitted to a major city hospital for intentional injury during a single year (1984-1985). This study focused on interpersonal assaultive injury, excluding sexual assault, child abuse, and self-inflicted injuries. Relevant injuries made up three-quarters of all admitted intentional injuries and represented a total of 671 patients (4.5% of all hospital admissions). The intentionally injured were compared to the catchment area population and to the remaining admitted hospital population, by age, sex, and race. Medical records of intentionally injured adolescents (n = 133) were reviewed and compared to a sample of adolescent homicide victims regarding the circumstance of the event and the relationship of victim to assailant. Relevant findings are that: (1) in the area served by this hospital, male adolescents are at relatively high risk for nonfatal intentional injury; (2) among adolescents, the majority of these intentional injuries are the result of interpersonal conflicts between acquaintances, paralleling the etiology of homicide: (3) a prevalence of missing data in the medical records of older male adolescents is symptomatic of the lack of attention that has been paid to understanding and preventing intentional injury among adolescents. It is concluded that: (1) more area-specific and hospital-based studies of intentional injury are needed as a guide to such preventive efforts; and (2) medical personnel providing acute care to victims of intentional injury are an important resource for this research and prevention effort. PMID- 2602210 TI - Preparing for the next decade: proceedings of the Third Annual National Child Abuse Conference. Philadelphia, March 16-17, 1989. PMID- 2602209 TI - Proceedings of the annual meeting of the American Academy of Pediatrics, Section on Emergency Medicine. Chicago, October 21-22, 1989. PMID- 2602211 TI - Pain management in the pediatric emergency department. PMID- 2602212 TI - Unintentional trauma to the penis. PMID- 2602213 TI - Affective disorders and anxiety in the child and adolescent. PMID- 2602214 TI - An integrative treatment approach to child and adolescent suicidal behavior. AB - The suicide rate for adolescents has tripled during the last 30 years in North America and many Western countries. Although some high risk factors have been defined, the literature is weak on the prevention and treatment issues. This article defines an integrative treatment approach for self-destructive behavior. This model attempts to integrate the well-recognized theoretical and therapeutic approaches such as biologic, psychodynamic, behavioral, cognitive, self-directed, strategic, experiential, and systemic frameworks. In the integrative approach, the therapist integrates the use of drug therapy and child, group, milieu, and family therapy, depending on the needs of each child. After a brief presentation of the author's comprehensive, in-depth study with 139 suicidal children and adolescents, the commonly seen family reactions to suicidal behavior were described. Family stage reactions of shock and fear, panic and action, guilt, resentment, reparation, and partial recovery are defined with case examples. The complementary nature of the supportive and therapeutic work for the families of suicidal children and adolescents with other preventative and therapeutic interventions is highlighted. PMID- 2602215 TI - Vascular transformation of lymph node sinuses--a diagnostic pitfall. Histopathologic and immunohistochemical study. AB - Histopathologic and immunohistochemical features in two cases of lymphoadenopathy caused by congestion are described. The diagnostic differences between this type of lymphoadenopathy and Kaposi's sarcoma are stressed. The histogenesis of the lesion is discussed and the term "stasis lymphadenopathy" is suggested. PMID- 2602216 TI - Bacterial endocarditis in a transplanted heart. AB - A 51-year-old man presented with an abscess in his sternotomy scar 33 months after orthotopic heart transplantation. After surgical drainage he developed a febrile illness which led to renal and pulmonary failure. Twenty-three days after the illness began, blood cultures grew Staphylococcus aureus and he died 11 days later. Post-mortem examination revealed acute bacterial endocarditis with dense colonies of gram-positive cocci on the mitral valve leaflets and microabscesses in the myocardium of the transplanted heart. PMID- 2602217 TI - Giant cell tumors of bone. An immunohistochemical study. AB - Immunohistochemical study of giant cell tumor of bone (GCT) was carried out utilizing a panel of monoclonal antibodies including those against lysozyme, alpha-antichymotrypsin (AACT), vimentin (Vim), M718, HLA-DR, S-100 protein, epithelial membrane antigen (EMA), leukocyte common antigen (LCA), KB90, factor VIII related antigen (F VIII) against stromal cells and giant cells in 20 cases of GCT, with one case of prolonged continuously cultured cells GCT (GT 15). The results showed that stromal cells could be divided into two subgroups. Mesenchymal stromal cells labelled only with vimentin and were regarded as being derived from undifferentiated mesenchymal cells of bone marrow, while macrophage like stromal cells labelled with antigens and were found to be present in mononuclear phagocytes. We believe this to be the first report that some stromal cells reacted positively with S-100 protein. Multinucleated giant cells were AACT and M718 positive, indicating their close relationship to macrophage-like stromal cells. The prolonged cultured cells accepted labelling with vimentin only indicating that all macrophage-like stromal cells disappeared after several subcultures and the only cells that could continue to be subcultured were the mesenchymal stromal cells. PMID- 2602218 TI - Dysplasia of the gallbladder. Its histogenesis and correlation to gallbladder adenocarcinoma. AB - A total of 50 cases of gallbladder dysplasia found adjacent to carcinoma were examined histologically and immunohistochemically for metaplastic changes in order to elucidate the characteristics of the dysplasia of the gallbladder. The incidence of metaplastic changes in the dysplastic mucosa such as the occurrence of endocrine cells, lysozyme-immunoreactive cells, goblet cells, and Paneth cells were 58%, 74%, 32%, and 22%, respectively. Based on the presence or absence of metaplastic changes, these 50 cases of dysplasia were divided into 40 cases (80%) of metaplastic type dysplasia showing at least one marker of metaplasia and 10 cases (20%) of non-metaplastic type dysplasia showing no metaplasia. On the other hand, these 50 cases of carcinoma were divided into 10 cases of non-metaplastic type carcinoma and 40 cases of metaplastic type carcinoma based on the presence or absence of metaplasia in the tumor tissue. The incidence of metaplastic changes in the dysplastic lesions was compared between the dysplasia adjacent to non-metaplastic type carcinoma and that adjacent to metaplastic type carcinoma. The incidence of metaplasia in the dysplastic mucosa adjacent to metaplastic type carcinoma was higher than that adjacent to non-metaplastic type carcinoma with a statistically significant difference. Moreover, the presence or absence of metaplastic changes was also examined in the surrounding dysplasia and non tumorous mucosa in each case. Most cases of metaplastic type carcinoma were surrounded by dysplasia with metaplastic changes and by metaplastic epithelium, whereas most cases of non-metaplastic type carcinoma were surrounded by dysplasia without metaplasia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602219 TI - Clinicopathological study of Ki-1-positive lymphomas. AB - We examined an antibody against Ki-1 antigen in 161 cases of malignant lymphoma, four of histiocytic sarcoma, and six of nonspecific lymphadenitis, using monoclonal antibody Ki-1, which is known to react selectively with activated lymphocytes, Reed-Sternberg cells, and Hodgkin's cells. Among them, 12 cases of malignant lymphoma demonstrated a diffuse positive cell membrane and/or cytoplasmic reaction of tumor cells and were categorized as Ki-1-positive lymphoma. Nine of these cases exhibited large cells with indented nuclei, distinct nucleoli, and abundant basophilic or amphophilic cytoplasm. Of the remaining three cases, two were of medium-sized and one of small-cell type. Immunologically, the 12 cases of malignant lymphoma demonstrated T-helper/inducer phenotype in six cases, B-cell in two case, and non-T, non-B in four cases. Tac and HLADR were positive in 9/12 and 4/5, respectively, and markers for histiocytes (lysozyme, alpha-1 anti-chymotrypsin, and OK-M1) were usually negative. Clinically, T-cell Ki-1-positive lymphoma was most likely to occur in the elderly, at extranodal sites, and had a rather poor prognosis (mean survival 35.5 months) as compared with B-cell and non-T, non-B lymphoma (7-52 months survival). PMID- 2602221 TI - Primary omental tumor with ultrastructural features of cellular schwannoma and absence of S-100 antigen reactivity. AB - We report a primary well-delimited, large mesenchymal omental neoplasm which appeared in a 58 year old man without neurofibromatous traces. The histological and ultrastructural features were consistent with a Schwann cell origin. However, repeated immunohistochemical reactions failed to demonstrate protein S-100 antigen reactivity in the neoplastic cells, the latter only expressing vimentin. The differential diagnosis with hemangiopericytoma is proposed. PMID- 2602220 TI - Multicentric angiofollicular lymph node hyperplasia associated with a solitary osteolytic costal IgG lambda myeloma. POEMS syndrome in a South American (Paraguayan) patient. AB - We report the case of a 46-year-old woman presenting with a disorder characterized by the association of multicentric Castleman's disease, organomegaly, a solitary IgA lambda myeloma with lytic bone lesions but no serum monoclonal peak, peripheral neuropathy and skin changes. This unusual association resulted in an incomplete form of that peculiar multisystem syndrome described under a variety of names: Crow-Fukase syndrome, Shimpo's syndrome, Takatsuki's syndrome, PEP syndrome or POEMS syndrome. The possible relationship between localized and multicentric Castleman's disease with myeloma or extramedullary plasmacytoma on one hand and on the other hand with polyneuropathy and the other symptoms of the POEMS syndrome is discussed. PMID- 2602222 TI - Multifocal adenomatous oncocytic hyperplasia in parotid glands with metastatic deposits or primary malignant transformation? AB - Rare tumorous lesions involving both parotid glands were found in a 90-year-old man at autopsy. The clinical course held together with the histopathological features of the parotid alterations, make it likely that they present a multifocal adenomatous oncocytic hyperplasia. Areas of clear cells and occurrence of papillary malignant foci lead to various differential diagnostic considerations. Series of therapeutic irradiation to both parotid regions with a latency period of 15-35 years perhaps induced multifocal malignant transformation in the oncocytic hyperplastic parotid tissue. PMID- 2602223 TI - Twisting of the spleen observed in a case of polysplenic disorder associated with situs viscerum inversus and Kartagener's syndrome. AB - The authors describe a rare example of polysplenic disorder observed in a thirteen year-old girl known to be affected by situs viscerum inversus and Kartagener's syndrome. The spleen consisted of ten "mini spleens" positioned along the gastric curve. The twisting of one of these was the cause of the surgical intervention which led to the discovery of the splenic malformation. Grossly, each spleen had its own peduncle depending on a single major peduncle, representing the splenic hilus. The overall weight was 260 g. The twisted spleen was blackish in colour, filled with blood and weighed 100 g. Histopathologically, no particular finding was observed. Although the preoperative diagnosis of polysplenic disorder is difficult, the knowledge of a basic malformative condition should lead to the search for this possibly associated malformation because of its clinical implications. PMID- 2602224 TI - What's new in the local immune response in cancer? AB - Malignant tumors in humans are commonly associated with an inflammatory infiltrate. The mechanisms that account for the accumulation of T-lymphocytes and macrophages--these cells comprise the major components of tumor infiltrates--in the vicinity of a growing tumor are not fully understood. Tumor specific and immunogenic antigens could not be demonstrated in most solid tumors of humans, in contrast to several experimental tumor models. Thus it is not proven in human malignancies that neoantigens expressed on malignant cells are the signal which initiates an inflammatory response that, immunohistologically, is comparable to mononuclear infiltrates present in allograft rejection. A variety of nonspecific factors including lymphokines released by tumor cells may also account for the accumulation of inflammatory cells at the tumor site. The difficulties to evaluate the functional role of the "local immune response" for tumor and host are even greater. Most tumors progress in the presence of mononuclear infiltrates. Do they progress in spite of or because of the action of the local immune response? Clinical, immunopathological, and experimental data suggest that both is right, and that at least four distinct properties of tumor-associated immune reactions exist: Regression, Selection, Modulation and Progression. These distinct properties will be discussed below, using mainly the malignant melanoma of the skin as a model for a malignant tumor in humans. PMID- 2602225 TI - Severe anaemia with unusual blasts in the bone marrow. PMID- 2602226 TI - Laboratory computers--the unfulfilled promise. PMID- 2602227 TI - Prune belly syndrome: clinicopathologic study of 29 cases. AB - The clinical course and the pathologic features of 29 patients with the prune belly syndrome (PBS) are reviewed. There were 26 males and 3 females. In addition to the classical triad of deficient abdominal musculature, urinary tract abnormalities, and cryptorchidism, a broader spectrum of other defects was found including musculoskeletal (58%) and gastrointestinal (31%) abnormalities. Genital anomalies were present in all three female patients. Many of these defects may be inapparent at birth, but are the cause of morbidity and mortality later in life. Severe urinary tract maldevelopment and pulmonary hypoplasia as part of the oligohydramnios syndrome was the most common cause of perinatal deaths. In these patients, major portions of the renal parenchyma were dysplastic, but in survivors, renal dysplasia, when present, was minor by comparison, and affected less than 1/3 of the parenchyma. Although several questions remain unanswered, we believe that the PBS results from the effect of one or more teratogenic agents on the somatic mesoderm, producing inappropriate mesenchymal development and inadequate mesenchymal-epithelial interactions that lead to abnormal development and dilatation of some of its derivatives (abdominal muscles, ureter, bladder, prostate, urethra, and gubernaculum). Although abnormalities in derivatives of the intermediate mesoderm (kidney) may also be produced by the injurious agent(s), they are more likely a result of urinary obstruction. Abnormalities in other organs and systems are the consequence of oligohydramnios. PMID- 2602228 TI - Solitary intestinal fibromatosis: a rare cause of neonatal obstruction. AB - Solitary intestinal fibromatosis (SIF) is an unusual cause of neonatal intestinal obstruction. A fibromatosis located in the first part of the duodenum, close to the pylorus, was associated with a focus of heterotopic pancreas and mimicked congenital pyloric stenosis. It illustrates the difficulties encountered in the diagnosis and surgical management of this condition. PMID- 2602229 TI - Congenital midline cervical cleft. AB - We present a case of congenital midline cervical cleft (CMCC), a sporadic lesion with a predilection for white females. It characteristically occurs in the midline ventral neck and consists of a cephalad skin tag, a mucosal surface, and a caudal sinus. There is an associated submucosal fibrous cord and interwoven bundles of skeletal muscle. This is occasionally tethered to the mandible and/or sternum causing neck contractures. CMCC is usually isolated, but rare cases have been associated with midline clefts of the tongue, lower lip, mandible, and sternum. The embryogenesis is unclear but arguments are given here that CMCC represents ectopic first branchial arch derivatives, including the lower lip and/or tongue. PMID- 2602230 TI - Walker-Warburg syndrome. PMID- 2602231 TI - Complications from in utero death of a monozygous co-twin. PMID- 2602232 TI - Progressive neonatal liver failure due to type C Niemann-Pick disease. PMID- 2602233 TI - Sarcoma arising in pulmonary mesenchymal cystic hamartoma. PMID- 2602234 TI - Cardiac arrhythmias during acute exacerbations of chronic airflow limitation: effect of fall in plasma potassium concentration induced by nebulised beta 2 agonist therapy. AB - The effect on cardiac rhythm of the fall in plasma potassium concentration induced by nebulised beta2-agonist therapy was studied in 20 patients admitted to hospital with an acute exacerbation of their reversible chronic airflow limitation. Arrhythmias considered serious or potentially life-threatening were recorded in 13 patients (65%). However, there was no significant increase in these arrhythmias in the hour following administration of nebulised beta2-agonist despite a significant fall in plasma potassium concentration during this period. PMID- 2602235 TI - A study of the dental health of patients undergoing heart valve surgery. AB - The mouth is a possible source of infection in patients receiving prosthetic heart valves. In this study, the dental health of such patients was found to be very poor. Whilst most of the patients were asymptomatic, only two were dentally fit and 65% required the extraction of one or more teeth. On average, patients had not attended a dental practice for more than 9 years. This level of dental neglect, in a group of patients particularly at risk, is alarming and this study indicates that a higher standard of oral care is still required and that a lack of symptoms does not indicate dental fitness. PMID- 2602236 TI - Lack of efficacy of phenytoin in the syndrome of inappropriate anti-diuretic hormone secretion of neurological origin. AB - Phenytoin has been proposed in the management of patients with the syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) of neurological origin who fail to respond to water restriction. We have conducted a prospective study in order to evaluate the role of phenytoin in the management of seven consecutive patients with SIADH of neurological origin which could not be controlled by limited water intake. Only one patient was successfully treated with chronic phenytoin regimen. This patient, like one previously reported, had suffered a basal skull fracture. It seems likely that in the majority of cases of SIADH of neurological origin phenytoin is ineffective on a long-term basis. PMID- 2602237 TI - Small bowel obstruction: a review of 264 cases and suggestions for management. AB - Two hundred and sixty-four cases of acute small bowel obstruction were retrospectively reviewed for the purpose of defining factors which could point to the presence of strangulated bowel. History, physical signs and investigations, including body temperature, X-rays, white blood count, and serum amylase, were not significantly different in the simple and strangulated groups. Although an elevated urinary white blood count and a palpable mass were more common in the strangulated group, they were not sufficiently reliable for early diagnosis of strangulation. In reviewing the literature, it is clear that all hernias with obstruction must undergo emergency surgery. Cases with intra-abdominal complete intestinal obstruction should also undergo emergency surgery. A more conservative attitude can only be taken when there is incomplete obstruction. PMID- 2602238 TI - Acute presentation of cystic fibrosis in an adult. AB - The case history of a female patient presenting at the age of 25 with cystic fibrosis is described. Despite longstanding significant respiratory symptoms, she did not attend hospital until she was 23 and then failed to appear for further investigations and treatment. At the age of 25, she was admitted with a severe lower respiratory tract infection and respiratory failure. Within 5 days, acute intestinal obstruction developed which was unresponsive to conservative therapy. At laparotomy the small bowel was obstructed just proximally to the ileocaecal valve by solid faecal material. Post-operatively, the diagnosis of cystic fibrosis was confirmed by quantitative pilocarpine iontophoresis tests. The literature is reviewed regarding the adult presentations of cystic fibrosis and the recommended treatment for distal intestinal obstruction syndrome. The presence of adult cystic patients within the community is emphasized. PMID- 2602239 TI - Adenotonsillar hypertrophy and cor pulmonale: clinical and echocardiographic correlation. AB - It is well recognized that upper airways obstruction by adenotonsillar hypertrophy can lead to cor pulmonale, but delays in diagnosis still occur, leading to an appreciable morbidity and even occasional mortality. In the case presented, echocardiographic recognition of right ventricular enlargement and abnormal pulmonary valve motion served to complement and confirm the clinical diagnosis. Following surgical relief of the airways obstruction, the echocardiographic examination usefully documented the regression in right ventricular size and the return to normality of pulmonary valve motion. PMID- 2602240 TI - Pathognomonic intracranial calcification. PMID- 2602241 TI - Progression of hydrocephalus during corticosteroid therapy for neurosarcoidosis. AB - We describe a patient with sarcoid meningitis and hydrocephalus who improved rapidly after initiation of oral prednisone therapy, but who later decompensated acutely and required an emergency ventriculoperitoneal shunt. Hydrocephalus associated with neurosarcoidosis may progress despite steroid treatment, even when symptoms have improved. If hydrocephalus associated with neurosarcoidosis is treated with corticosteroids and without a shunt procedure we suggest that the corticosteroids should be continued at high doses for a prolonged period. PMID- 2602242 TI - Thrombocytopenia--radial aplasia (TAR) syndrome with associated immune thrombocytopenia. AB - We report a 10 year old girl with congenital thrombocytopenia with absent radii (TAR) syndrome. Unusually this patient has shown no abnormal bleeding tendency despite numerous orthopaedic procedures. There is evidence of an associated immune component to the thrombocytopenia which has not been previously documented. PMID- 2602243 TI - Spontaneous resolution of cervical spinal epidural haematoma. AB - A patient with a spontaneous cervical spinal epidural haematoma is described. Surgical decompression is generally regarded as mandatory. There was complete clinical and radiological resolution with non-operative treatment. This is the fifth recorded case of spontaneous resolution of spinal epidural haematoma. In selected patients with incomplete and non-progressing deficit, conservative management may be possible. PMID- 2602244 TI - Tumours of the pancreas as a sequel to abdominal irradiation. AB - Two cases of tumours arising in or near the pancreatic head are reported in patients previously treated with abdominal irradiation for testicular tumours. These are only the third and fourth such cases to be reported and they suggest that second cancers may develop as a result of abdominal irradiation for malignant disease. PMID- 2602246 TI - Hepatic abscess and cystic fibrosis. PMID- 2602245 TI - Hyperammonaemic coma in ureterosigmoid urinary diversion. AB - We report on a patient with ureterosigmoid anastomosis, who presented with recurrent episodes of confusion, agitation and aggressive behaviour, culminating in coma. Investigations revealed profound hyperammonaemia, which responded to treatment with sodium benzoate and sodium phenylacetate. No definite cause was found for the abnormality, apart from possible urinary tract infection. The patient remains well on a protein restricted diet with mildly elevated levels of plasma ammonia. PMID- 2602247 TI - Peritoneal dialysis in a patient with haemophilia and chronic renal failure. PMID- 2602248 TI - Porphyria cutanea tarda and human immunodeficiency virus: two new cases. PMID- 2602249 TI - Renal and hepatic impairment in association with diclofenac administration. PMID- 2602250 TI - Microscopic polyarteritis: clinical features and treatment. AB - The clinical features, treatment and survival of 36 patients with microscopic polyarteritis diagnosed between 1957-1988 have been reviewed. All had a focal segmental necrotizing glomerulonephritis on renal biopsy with evidence of a small vessel vasculitis. Most had a prodromal illness of less than 1 month. Severity of renal disease varied from microscopic haematuria which has a good prognosis to acute oliguric renal failure which carries a high mortality. The prognosis of microscopic polyarteritis can be improved if the condition is recognized early and treated with steroids and cyclophosphamide. PMID- 2602251 TI - Yield of the admission complete blood count in medical inpatients. AB - The clinical efficacy of routine admission complete blood count was evaluated in 302 patients admitted to internal medicine wards of a university teaching hospital. Patient medical problems, physical findings and medication history were evaluated by preset criteria to determine the proportion of tests performed for screening and the proportion of test results directly influencing patient management. Of the 282 complete blood counts performed, 80% were ordered routinely with no medical indications (screening tests). An haemoglobin abnormality was found in 16.7% of the patients, leucocyte abnormality in 16.1% and platelet abnormality in 4.6%. However, these results directly influenced patient management in only one case (0.14%). It is concluded that the utility of screening admission complete blood counts in medical inpatients is negligible. PMID- 2602252 TI - Toxic reaction to inhaled paint fumes. AB - An acute confusional state was observed to follow heavy exposure to polyurethane gloss paint fumes in a previously healthy 60 year old man. This state remitted over a 3-day period, but was followed by transient bone marrow suppression and evidence of liver cell damage. The corroborated absence of other toxins and the temporal association of exposure to paint fumes suggest that a volatile paint component was responsible. White spirit is the major volatile solvent in polyurethane gloss paint. Ingestion of related aliphatic hydrocarbons has been reported to cause nausea, drowsiness and hepatotoxicity, but these symptoms have not previously been documented following excessive inadvertent inhalation of paint fumes. PMID- 2602253 TI - Strychnine poisoning as an unusual cause of convulsions. AB - A fatal case of strychnine poisoning is presented. The patient vomited then suffered a series of tonic convulsions which were triggered by tactile stimulation. In between paroxysms he was initially alert. Eventually the patient became comatosed due to anoxia and had a cardiac arrest. He presented with a marked metabolic acidosis and rapidly developed renal failure caused by acute rhabdomyolysis. This clinical picture is classical for strychnine poisoning and the complications which the intoxication produces. Attention is drawn to the fact that survival can even follow the ingestion of very large doses of strychnine providing there is no delay in diagnosis and treatment. PMID- 2602254 TI - Intracranial abscess complicating diverticulitis with CT scan mimicking primary glioma. AB - The case of a 64 year old woman with diverticulitis complicated by a metastatic cerebral abscess is reported. Presentation was atypical and investigations were misleading; the computed tomographic scan was interpreted as showing a glioma. This case demonstrates that malignancy should never be assumed and the importance of making a histological diagnosis. Once the abscess was drained the patient made a full recovery with resolution of her neurological deficits. PMID- 2602255 TI - A paraspinal shadow. PMID- 2602257 TI - Use of adrenal arterial embolization in severe ACTH-dependent Cushing's syndrome. AB - The management of a patient with severe Cushing's syndrome due to ectopic ACTH produced by a medullary carcinoma of the thyroid is described. Initial treatment with maximal adrenolytic medical therapy and two attempts at bilateral adrenal venous infarction had failed to control the disease, and she was at that time unfit for surgery. Subsequent use of bilateral adrenal arterial embolization enabled medical therapy to produce sufficient control of the Cushing's syndrome to allow bilateral adrenalectomy to be performed successfully, with resultant cure of the excessive cortisol production. PMID- 2602256 TI - Meningeal infiltration by non-myelomatous IgD-secreting plasma cell dyscrasias. AB - Two cases of meningeal invasion by non-myelomatous plasma cell dyscrasias--a plasma cell leukaemia and an extramedullary plasmacytoma--are described. Both were secretors of IgD paraprotein and both were diagnosed in life, characteristics which we have not found in any other published case of plasma cell leptomeningitis. Analysis of our patients and of another 25 cases suggests as predisposing factors of meningeal invasion the male sex, presentation in the form of plasma cell leukaemia, presence of the IgD paraprotein and tumoral involvement of pleura, lung, pericardium and testicles. Aggressive treatment of this neurological complication controlled the meningeal disorder in some cases. However, the majority died of disseminated disease in spite of systemic chemotherapy. Until an effective treatment can be found, able to maintain remission or cure the systemic disease, prophylaxis of the central nervous system in plasma cell dyscrasias does not appear to be advisable. PMID- 2602258 TI - Painless giant cell thyroiditis. AB - We describe an atypical case of subacute thyroiditis affecting a 50 year old patient with long lasting fever, weight loss, malaise and a high erythrocyte sedimentation rate. Cytological examination of the thyroid gland showed the classic granulomas with giant cells. However, the patient had neither painful enlargement of the gland nor thyrotoxicosis. This case, as well as others previously described, probably represents a new subtype of subacute thyroiditis, painless giant cell thyroiditis. The presence of painless giant cell thyroiditis should be considered in any patient with undiagnosed pyrexia, weight loss and elevated ESR. PMID- 2602259 TI - The Vogt-Koyanagi-Harada syndrome: association with hypothyroidism and diabetes mellitus. AB - A 45 year old Saudi male with poliosis, alopecia areata, vitiligo, anterior uveitis, inflammatory changes in the posterior pole of the retina and paraparesis presented with features of the Vogt-Koyanagi-Harada syndrome, uncontrolled diabetes mellitus and hypothyroidism. To the best of our knowledge the association of diabetes mellitus and hypothyroidism in this syndrome has not been reported previously. PMID- 2602260 TI - Myocardial abscess and sternal osteomyelitis following myocardial infarction and resuscitation. AB - A 58 year old man presented with an anterior myocardial infarction requiring repeated resuscitation. He had impaired glucose tolerance. He died five weeks later and post-mortem examination revealed a myocardial abscess and sternal osteomyelitis due to Staphylococcus aureus. These had not been apparent clinically. The possible aetiology and difficulties in diagnosis are discussed. PMID- 2602261 TI - Babesiosis: under-reporting or case-clustering? AB - Babesiosis is a tick-borne protozoan disease which principally affects animals but occasionally affects humans. Cases have been reported from many parts of Europe with no evidence of case-clustering. We report the second case of babesiosis from a small area in the west of Ireland. PMID- 2602262 TI - Intestinal ischaemia associated with phaeochromocytoma. AB - The present case report describes a patient with an adrenal phaeochromocytoma who presented with infarction of the small intestine. The clinical features, diagnosis and treatment of this case are described. Despite excision of the tumour and necrotic intestine, this patient died in the postoperative period from overwhelming sepsis and multi-organ failure. Special reference is made to the delayed effects of established intestinal ischaemia on immune function and it is suggested that this was major contributory factor to the fatal outcome in the present case. The onset of gastro-intestinal symptoms in patients with phaeochromocytoma should suggest the possibility of imminent gut ischaemia and indicate the necessity for prompt excision of the tumour. PMID- 2602263 TI - Carcinoid syndrome without liver metastasis. AB - The carcinoid syndrome generally occurs due to metastasis of a carcinoid tumour in the liver. A patient is presented who had carcinoid syndrome due to abdominal disease without hepatic metastasis. PMID- 2602264 TI - Simultaneous occurrence of systemic lupus erythematosus and coeliac disease-like features. AB - Involvement of the gastrointestinal tract in systemic lupus erythematosus is well documented but small intestinal malabsorption is a rare event. We report a 27 year old woman with systemic lupus erythematosus who had malabsorption and coeliac-like changes on intestinal biopsy. This is the eighth reported case of this association the significance of which is discussed. PMID- 2602265 TI - Listeria monocytogenes meningitis in previously healthy adults. PMID- 2602267 TI - Coercion or choice? PMID- 2602266 TI - Is intestinal metaplasia a risk for gastric carcinoma? PMID- 2602268 TI - Whither general practice? PMID- 2602269 TI - Treating viral warts with a novel salicylic acid gel. PMID- 2602270 TI - Intestinal malrotation--a missed diagnosis. PMID- 2602271 TI - The sleepless child. PMID- 2602272 TI - Acute phase management of myocardial infarction. AB - Many deaths from acute myocardial infarction occur before hospital admission. Provision of resuscitation by GPs, ambulance personnel and the general public has been shown to improve early mortality. The impact of thrombolysis on prognosis is also discussed. PMID- 2602273 TI - Dealing with 'difficult' patients--what goes wrong. AB - Tactful management of difficult situations can avoid the risks of violence. Being aware of non-verbal signals and using counselling skills helps GPs handle highly emotional patients. In the street or in the home, common sense steps will help protect doctors visiting patients. Recognising our own feelings is important too. PMID- 2602274 TI - GPs' differing responses to out-of-hours calls. AB - After noticing trainer-trainee differences in the proportion of patients visited, a three-month audit of all out-of-hours requests and calls was performed. A wide variation of response was found among doctors on the rota. Those more likely to visit were also more likely to prescribe. A large proportion of the user population was either very young or very old and had an annual consultation rate nearly three times the mean for the practice as a whole. PMID- 2602276 TI - Legal and ethical matters. PMID- 2602275 TI - Maintaining remission in mood disorders. AB - The natural history of bipolar and unipolar affective disorders is for increasing severity and frequency of attacks as the patient ages. A major challenge for clinicians is the initiation and maintenance of prophylaxis. PMID- 2602277 TI - Enterobius vermicularis. AB - The benefits of a ring flash in photographing an orifice can be seen in this interesting case where the main subject area is clearly visible. When photographing minors, the legal implications of the subject material needs to be considered to avoid contravening the Protection of Children Act. PMID- 2602278 TI - Recent advances in urology. PMID- 2602279 TI - Testicular self-examination. PMID- 2602280 TI - Chronic renal failure and transplantation. AB - Chronic renal failure may be treated by haemodialysis, continuous ambulatory peritoneal dialysis, or renal transplantation. The advent of CAPD has allowed many more patients to be treated, especially the elderly and very young children. Transplantation is being offered increasingly over a wider age range and patients may now expect to have a 75 per cent chance of keeping a kidney for one year and a 60 per cent chance of keeping it for five years. PMID- 2602281 TI - Rugby. AB - Many GPs want to learn the basics of how best to manage the increasing numbers of patients seen in the surgery with sports injuries. To create a more satisfied patient, this should include how to advise patients in simple management of the acute injury as well as preventive measures. Dr Ben Gilfeather writes of the common injuries to muscles encountered in rugby and urges GPs to take an opportunistic approach to educating youngsters involved in sport. PMID- 2602283 TI - Assessing knowledge about AIDS. PMID- 2602282 TI - Allergy research in the 1990s. PMID- 2602284 TI - How to help families with mental handicap. AB - Mentally handicapped children and adults are today cared for within the community. Their families have particular needs and fears and require support from their GP. PMID- 2602285 TI - The assessment of disability caused by migraine. AB - Migraine is common and can be disabling. Simple systems for rating the degree of disability and assessing the prevailing migraine threshold are described. Together they are relevant in considering both the diagnosis and treatment of the condition. PMID- 2602286 TI - The management of varicose veins. AB - The treatment of most of the complications of varicose veins lies in a knowledge of the pathophysiological mechanisms at work and the appropriate management of the veins themselves. PMID- 2602287 TI - The MRCGP examination. AB - In the examination, no amount of bluff and veneer will disguise a lack of preparation. However, bad technique will take the shine off a good performance. PMID- 2602288 TI - Medial mental sinus. AB - Lighting is an important tool of the photographer, since it can be used to create shadows to highlight the condition under study. For photographs such as the one shown, oblique lighting is essential. PMID- 2602289 TI - Allergy. PMID- 2602290 TI - Anticipating hayfever. AB - An anticipatory approach to hayfever, using available data on the timing of peak pollen levels, could help GPs deal with the seasonal increase in workload caused by this allergic disease. A stepwise approach to treatment is also suggested. PMID- 2602291 TI - Food intolerance. AB - There are two categories of food intolerance: food idiosyncrasy, due to metabolic abnormality, and food allergic disease. Both are common and complex, especially in children, and need skilled and experienced management. The GP's role is in early recognition, and the continuation of overall care. PMID- 2602292 TI - Allergens and irritants. AB - The range of diseases caused by respiratory allergens and irritants is wide because they trigger different pathophysiological mechanisms. Surprisingly, though smoking promotes asthma it exerts the opposite effect on the development of extrinsic allergic alveolitis. PMID- 2602293 TI - Hockey. AB - Hockey players as a whole do not suffer from the same degree of overuse injuries that many athletes experience. However, they do sustain a large number of contact injuries. A few minutes explanation as to the immediate treatment required may well reduce the number of times the player has to return to the surgery in the future. PMID- 2602294 TI - A retrospective survey of children with recurrent otitis media. PMID- 2602295 TI - What is dermatosis papularis nigra? PMID- 2602296 TI - Cancer of the prostate--where are we now? PMID- 2602297 TI - Neurosis or psychosis? AB - The management of patients who attend the surgery requesting psychotropic medication is complicated by the inadequate classification of neuroses and the difficulty in distinguishing between neurotic and psychotic depression. Moreover, patients have lives to lead and know that there is treatment available as they have often been given tablets before. PMID- 2602298 TI - Accident and emergency abusers. AB - Inappropriate attendances at Accident and Emergency departments is a problem affecting all such services around the UK. Different approaches have been and are being tried. We report the results of a detailed study of this subject and discuss the main cause of the abuse of this facility. PMID- 2602299 TI - Lifestyle intervention in hypertension. AB - Patients are often interested in taking some responsibility for treating their own illnesses, especially in a symptom-free condition such as hypertension. Confusing information is available on non-pharmacological measures, which often results in none of these treatments being offered to the patient. This review discusses what is of value, what may be helpful and what is likely to be worthless. PMID- 2602300 TI - Is living in a slab block depressing? AB - The level of depression in 25 to 34-year-old, married women was assessed in relation to type of accommodation. The highest depression ratings were in women living in slab blocks and the lowest were in those living in brick houses in conventional streets. PMID- 2602301 TI - Preferences in the treatment of vaginal candidosis. AB - A recent study of the management of vaginal candidosis in general practice is compared here with a similar study in 1985. Single-day therapy has become more popular for acute episodes, but candidosis is a relapsing condition and there are many criticisms of the methods of treatment currently available. PMID- 2602302 TI - Advances in neonatal intensive care. AB - Since it became a specialty in its own right; neonatal intensive care has continued to expand rapidly. The aim of this article is to provide an 'up-date' on the technological and clinical advances made to improve the survival and long term outlook for preterm babies. PMID- 2602303 TI - Sigmoidoscopy in the practice. AB - This article describes the advantages of using the rigid and flexible sigmoidoscopes for diagnosis and management of large bowel disorders in the surgery. The results of our first years flexible sigmoidoscopy are discussed. PMID- 2602304 TI - Irritable bowel syndrome--making the diagnosis. AB - Irritable bowel syndrome need not be a diagnosis of exclusion. It can be made with confidence on clinical grounds, without wasting secondary care resources or increasing the patient's anxiety by unnecessary investigations. PMID- 2602305 TI - Endoscopy: a patient's view. AB - Patients with inflammatory bowel disease have many sigmoidoscopies and colonoscopies, these could be made less unpleasant by good dialogue and mental preparation. Follow-up by a GP instead of a consultant may also help. PMID- 2602306 TI - Football. AB - Ever-changing factors dictate susceptibility to injury in football, including weather and ground conditions (hard, muddy, frosty, slippery, sand covered ground), and the time of the season--overuse injuries in late season, acute sprains earlier. A combination effect ensures that match risk factors are never the same. Muscle tears and knee injuries are among the commonest injuries encountered. PMID- 2602307 TI - GP courses in the future. PMID- 2602308 TI - Stress and GPs. PMID- 2602309 TI - What is molluscum contagiosum? PMID- 2602310 TI - An elderly care clinic protocol in practice. PMID- 2602311 TI - An elderly patient with recurrent falls. AB - Many elderly patients have conditions which may not merit hospital admission but leave them in danger at home. The situation becomes more difficult if they refuse alternative accommodation and there is no family support. PMID- 2602312 TI - The diagnosis and management of the discharging ear. AB - Ear discharge is a relatively common symptom and reflects a range of pathology. Time given to aural toilet is well spent as it allows a more precise diagnosis and better access for the therapeutic agents. PMID- 2602313 TI - Psychological factors in cardiac rehabilitation. AB - Patients who are recovering from myocardial infarction or coronary surgery may have psychological symptoms but they are not psychiatric patients. Their emotional responses are normal. With appropriate psychological support, they will be able to adapt to and master the changes in their lives. PMID- 2602314 TI - Tuberculous and granulomatous mastitis. AB - Granulomatous breast diseases are rare and may be indistinguishable clinically from carcinoma. Four cases illustrating the various modes of presentation and diagnostic difficulties are presented. Guidelines for management are suggested. PMID- 2602315 TI - Four cases found at screening in general practice. AB - Individual cases can influence GPs more than carefully documented statistical arguments from population surveys. These four case histories illustrate that both specific and opportunistic screening may be needed if all patients at risk are to be identified. PMID- 2602316 TI - UTI: a practical approach to management. AB - Most patients with cystitis can be managed without investigation. There is no evidence that recurrent infection in women leads to a rise in blood pressure, serum urea concentration or kidney scarring. However, children require an entirely different approach because of the risk of renal scarring. PMID- 2602317 TI - Dacrocystitis. AB - In clinical photography, two views are often better than one to maximise the amount of information available to the viewer. Photographers should not endeavour to record everything in one shot. PMID- 2602318 TI - Peptic ulcer disease. AB - Many of the drugs available for treating peptic ulcer disease have a series of possible overlapping actions on various stages both of acid suppression and mucosal defence, but in certain situations one drug may be better than another. More research is needed to clarify the aetiology of peptic ulcer disease so that treatment can be improved. PMID- 2602319 TI - Coping with stoma care in the community. AB - On average, each GP looks after only five or six patients with a stoma and has little scope for developing expertise in stoma management. Stoma care nurses can provide an improved service for patients, and may also keep prescribing costs down. PMID- 2602320 TI - Evaluation of jaundice in general practice. AB - Though there are many causes of jaundice, the GP's role is to differentiate that which is secondary to obstruction from that which is caused by viral hepatitis. Useful laboratory tests for both have changed in recent years and the diagnosis and treatment of extrahepatic obstruction has been revolutionised by endoscopic techniques. PMID- 2602321 TI - Gastrointestinal infection. AB - Rotavirus and various types of E coli can cause life-threatening vomiting and diarrhoea in children. Food poisoning and traveller's diarrhoea cause problems for adults. PMID- 2602322 TI - Cricket: fast bowler's back and thrower's shoulder. AB - Preventive measures are important in cricket. Although not associated with as high an incidence of injury as contact sports, sudden bursts of extreme exertion after long periods of inactivity in cricket carry their own morbidity. PMID- 2602323 TI - Process and outcome. PMID- 2602324 TI - Counselling and GPs. PMID- 2602325 TI - Nausea, vomiting and the efficacy of post-coital contraception. PMID- 2602326 TI - Suspicion of sexual abuse. PMID- 2602327 TI - Severity of asthma: parent's assessment versus the physician's. PMID- 2602328 TI - Cutaneous horn. PMID- 2602329 TI - Spiritual healing in a medical context. PMID- 2602330 TI - Comparing urban and rural hospice services. AB - Hospice care has flourished in the past 20 years and now provides a wide range of services. This study compares the operation of an urban hospice with that of a smaller rural hospice. The implications of the underuse of some of the services are discussed. PMID- 2602331 TI - Hepatitis B vaccination and GPs. AB - Doctors seem ambivalent to their own health needs even though, when it comes to infectious diseases, their families are also at risk. This study looks at GPs' attitudes to getting themselves vaccinated against hepatitis B. Despite the risk, 21 per cent of GPs have no intention of being vaccinated. PMID- 2602332 TI - Hand, foot and mouth disease. AB - Standardisation is vital if the clinical images are to be used for monitoring any changes in the patient's condition. The two images can be cut and mounted in one 35 mm mount for comparison. PMID- 2602333 TI - Neurology. PMID- 2602334 TI - The diagnosis of epilepsy. AB - Epilepsy is a common condition with many social and medical implications, but it is not the only cause of seizures. It is important to make an accurate diagnosis after any clinical event that appears to be a fit. PMID- 2602335 TI - Headache. AB - Headache is one of the commonest problems to face the family doctor and hospital practitioners. Though migraine and tension headaches are the most common, other types could reflect serious underlying structural causes. Accurate diagnosis can usually be made from a complete history and examination. However, referral of some patients to a specialist clinic is inevitable. PMID- 2602336 TI - Transient ischaemic attacks. AB - Transient ischaemic attacks carry an increased risk of subsequent stroke, but death is more likely to result from myocardial infarction than from cerebral causes. Modification of risk factors, medical treatment and surgical intervention all have a role in management. PMID- 2602337 TI - Weakness, numbness, tingling and multiple sclerosis. AB - Multiple sclerosis is the most common serious neurological disease in young patients but it is not the only cause of paraesthesiae. Such sensory symptoms occur frequently and reflect a variety of underlying conditions. PMID- 2602338 TI - Tremor and Parkinson's disease. AB - Persistent tremor is a worrying symptom for patients but Parkinson's disease is not the most common cause. A careful history and clinical examination will usually provide the diagnosis. PMID- 2602339 TI - Childrens' unsupervised sports. AB - Childrens' injuries are often trivial, but this should not lead to complacency as the spectrum of possible problems is different from that in adults. Moreover, their examination is much more difficult and clinicians must be thorough so as not to miss concurrent pathology. PMID- 2602340 TI - Hospital ethics committees: purpose, composition, characteristics. PMID- 2602341 TI - Speed of growth of melanoma: statistical analysis of the average ages of patient groups. AB - Based on data from 1,657 cases, the average age of patients with melanoma of the same type, level, resp. thickness was calculated. It was shown that the average age of the melanoma patients increased with progressive tumor growth, i.e., with increasing level and thickness. The time span for thin (less than 0.75 mm thickness), superficial spreading melanoma (SSM) to reach the level of a far advanced tumor with a thickness of more than 3.00 mm was 7.8 years. For nodular melanomas (NM), the corresponding period was 9.5 years. Longer intervals were determined by analysis of the data according to tumor levels. The difference in the average age of patients with early invasive SSM (level II) as compared with patients with level V tumors was 11.4 years. Patients with level V NM were on the average 10.0 years older than patients with level III NM. Differences in the average age of patients with SSM or NM from one level to the other ranged between 3 and 4 years (median: 3.9 years). The differences in the thickness of the groups were similar (median: 3.1 years). PMID- 2602342 TI - Characterization of IIB-MEL-J: a new and highly heterogenous human melanoma cell line. AB - A highly heterogeneous cell line, IIB-MEL-J, was established from a human metastatic melanoma. This cell line contains small cells, dendritic cells, and megacells with multiple nuclei. IIB-MEL-J expresses S 100, cytokeratin intermediate filaments and the gangliosides GD2 and GD3. It requires growth factors (insulin, EGF, and transferrin) and antioxidants for optimal growth. When plated under optimal conditions, IIB-MEL-J grows with a doubling time of 70-80 hours. The cells may be fractionated by Percoll gradient centrifugation into several subpopulations (A, B, and C) with different characteristics. Subpopulation A is the slowest growing, and most of the DNA-synthesizing cells are concentrated in fractions B and C. Every subpopulation expresses S 100 and cytokeratin intermediate filaments, whereas only subpopulation B and C express GD2 and GD3. Pigmented cells are concentrated mainly in subpopulation C. Cytogenetic analysis of IIB-MEL-J revealed extensive chromosomal alterations, including a highly heterogeneous chromosome number and chromosomal rearrangements, gains, losses, isochromosomes, and double minutes. This highly heterogeneous cell line may be helpful to study cellular differentiation and interaction between different subpopulations in human melanoma. PMID- 2602343 TI - [The effect of chemical modification of ribonuclease A by serum albumin on its catalytic properties]. AB - The effect of chemical modification of ribonuclease A on its catalytic properties was studied. The kinetic parameters were calculated by using the Eisental and Cornish-Bowden direct linear plot. The Km value found for ribonuclease A conjugates with human serum albumin are comparable with those for the native enzyme whereas the Vmax value of the modified enzyme exceeds the maximum velocity of the enzymatic reaction of native ribonuclease A. PMID- 2602344 TI - [Chromatography of water-soluble porphyrins and their conjugates with proteins]. AB - The chromatographic behaviour of tetra- and octacarboxylic porphyrins and tetra (p-sulphophenyl)-porphin was being studied by HPLC using Protein Pak and TSK-type gel permeation columns. The mobility of the porphyrins on the carriers depended on the ionic strength of the eluating buffer Tris-HCl. The conditions for separation of the porphyrins and their protein conjugates were optimized. The separation was performed under mild conditions with minimum denaturation of conjugates. The purification technique can be used to separate porphyrin conjugates with various proteins. The technique can be also used in conventional column chromatography on Toyopearl supports. PMID- 2602345 TI - [The myocardial contractile function and central hemodynamics of patients with insulin-dependent diabetes mellitus during treatment]. AB - The results of echocardiographic investigation of 48 patients with type I diabetes mellitus (DM) were compared: 48 patients received routine therapy including diabetic management, insulin and vitamin therapy, 32 received this type of therapy plus a complex consisting of inosine, benphothiamine and pyridoxal phosphate. A considerable decrease in myocardial contractility and hemodynamic disorder were revealed against a background of DM decompensation in both groups of patients. Clinical improvement resulting from the use of the above complex showed good correlation with a positive course of echocardiographic values of myocardial contractility and pumping function. Elimination of myocardial insufficiency was accompanied by an increase in the stroke volume, ejection fraction, the rate of circulatory shortening of myocardial fibers, left ventricular mass, and a decrease in end diastolic and systolic volumes. The second type of therapy was well tolerated by the patients and made it possible to considerably lessen myocardial insufficiency and reduce a period of treatment in hospital as compared to routine therapy. PMID- 2602346 TI - [Thyroid antibodies in autoimmune diseases of the thyroid and their dependence on the presence of autoantigens]. AB - Autoimmune thyroid diseases (especially diffuse toxic goiter) are characterized by a higher frequency of the detection and concentration of serum thyroglobulin. The frequency of the detection of antibodies to thyroglobulin in Hashimoto's thyroiditis was higher and their concentration lower than in diffuse toxic goiter. The frequency of the detection of antibodies to microsomal thyroid antigen in autoimmune thyroid diseases was lower than that of antibodies to thyroglobulin and did not depend on a type of disease. In diffuse toxic goiter the level of antibodies to thyroglobulin showed positive correlation with the level of antibodies to microsomal antigen and negative correlation with serum thyroglobulin concentration. In Hashimoto's thyroiditis the level of antibodies to thyroglobulin correlated with the level of serum thyrotropin. One-six years after thyroid extirpation serum thyroglobulin was practically absent in patients with Hashimoto's thyroiditis, and the frequency of the detection of thyroid autoantibodies (especially antimicrosomal ones) was sharply decreased. PMID- 2602347 TI - [Immunological reactivity and the HLA system antigens in patients with autoimmune thyroiditis and nodular euthyroid goiter]. AB - Factors of nonspecific resistance, cellular and humoral immunity were investigated before operation in 84 patients with nodular euthyroid goiter and in 50 patients with autoimmune thyroiditis, 50 patients were investigated in the long-term postoperative period. Class I HLA antigens were investigated in 205 patients. Humoral changes of immune homeostasis (hyper-production of antithyroid antibodies, an increase in the level of IgM and IgG against a background of the raised number of peripheral blood B-cells, a decrease in the level of lysozyme), disorder of the cellular factor of immunity (specific sensitization of T lymphocytes to thyroid antigens, a decrease in the number of T-lymphocytes, especially T-suppressors) were detected in autoimmune thyroiditis. Immunological changes in nodular euthyroid goiter were characterized by T-cell sensitization to thyroid extract and microsomal antigen against a decrease in the total number of T-lymphocytes. In most patients with nodular goiter immunity indices after operation returned to normal whereas in patients with autoimmune thyroiditis they showed no tendency to improvement. These data as well as an increase in the frequency of HLA-A11, HLA-A19 and HLA-B8 were indicative of genetically determined primary nature of immune disorders in autoimmune thyroiditis. It was not typical of nodular euthyroid goiter in which an autoimmune process seemed secondary, occurring in response to damage of thyroid tissue by a growing nodule. PMID- 2602348 TI - [Changes in the immune status in primary hypothyroidism]. AB - A majority of patients with primary hypothyroidism demonstrated shifts in the immune status manifested in a decrease in the number and function of T lymphocytes, an increase in the sensitization of lymphoid cells to thyroglobulin, the level of B-lymphocytes, serum immunoglobulins, the titer of antihyroglobulin antibodies and circulating immune complexes. The frequency and expression of immune disorders were in direct relation to the severity of disease. The most noticeable changes were detected in spontaneous-hypothyroidism. A differentiated use of immunoreactive drugs (glucocorticoids, splenin) in patients with spontaneous hypothyroidism taking into account the severity of disease and immunological indices, enhanced the effectiveness of replacement therapy, reduced the time of achieving replacement therapy, reduced the time of achieving clinical remission and contributed to the normalization of biochemical and immunological indices. PMID- 2602349 TI - [The use of nuclear magnetic resonance in the diagnosis of hypophyseal adenomas (preliminary report)]. AB - The paper is concerned with the use of a new tomographic method based on the principle of nuclear magnetic resonance (NMR-tomography) in the diagnosis of adenohypophyseal diseases. A NMR-tomograph with a resistive magnet (0.234 T) was employed. Altogether 15 patients with the most common types of hypothalamo hypophyseal diseases including Itsenko-Cushing disease (6) of various degrees of severity, hyperprolactinemic hypogonadism (8), and one patient with acromegaly were investigated. NMR-tomography was shown to possess a high informative value permitting assessment of the presence of adenohypophyseal pathology without irradiation of a patient. NMR-tomography combined with routine methods of examination of patients with hypothalamohypophyseal pathology (roentgenography, computerized tomography, hormonal investigation) made it possible to improve considerably early diagnosis of pituitary adenomas and to specify the volume and type of tumor growth. PMID- 2602350 TI - [Clinical assessment and prognosis of the complications of the corticosteroid therapy of Addison's disease patients]. AB - Clinical and mathematical analysis was used for clinical assessment of specificities of the frequency of manifestations and combinations of complications in 87 patients with Addison's disease on corticosteroid therapy. Probability of the appearance of at least one of several complications or the combined appearance of several complications was established. The appearance of at least one of several complications in combination of excess body mass with other complications of the circulatory and digestive systems as well as one of several cardiovascular disorders could be predicted with the highest probability. Arbitrary discontinuation of corticosteroid therapy did not cause immediate clinical signs of the abolishment syndrome though in increased the probability of addisonian crisis development. PMID- 2602351 TI - [Restoration of the child-bearing function in a family as a result of the effective treatment of the hyperprolactinemia syndrome in the husband and wife]. PMID- 2602352 TI - [Effect of oxythiamine disulfides on the pancreas and thyroid of rats]. AB - Single administration of oxythiamine (200 mg/kg) or an isomolar amount of oxythiamineamyldisulfide to rats does not change the content of insulin in 72 h, whereas oxythiaminehexyldisulfide slightly increases the blood level of the hormone. Oxythiamine and its disulfides cause changes of the thyroid indicating considerable suppression of its function. It is assumed that hormonal mediation of oxythiamine nonspecific metabolic effects results predominantly from the involvement of the thyroid hormones rather than insulin. PMID- 2602353 TI - [Comparative evaluation of the lipid metabolic indices of children with a hereditary predisposition for diabetes and in manifest diabetes mellitus]. AB - The paper is concerned with the results of investigation of serum lipid, phospholipid and lipoprotein spectra in 31 sibs, 100 children with diabetes mellitus (DM), 83 women in birth with DM and their fetuses. This study showed a necessity of planned investigation of sibs not only for the detection of glucose tolerance but also of primary and secondary dyslipemia. In children with manifest DM the ratio of lipid, phospholipid and lipoprotein fractions was disturbed and depended upon a degree of compensation, a period of disease and a dose of insulin. The type of changes in the women in birth with DM was the same as during pregnancy: there was an increase in the concentration of total lipids and some of their fractions: nonesterified fatty acids, triglycerides, cholesterol, and atherogenic lipoproteins. Liposynthetic activation observed in infants born to DM mothers, was associated with the metabolic effects of insulin, of which a degree of hypersecretion seemed to determine the type of lipidograms. PMID- 2602354 TI - [The dimer form of porcine prolactin]. AB - The properties of a previously isolated disulfide form of pituitary porcine prolactin (pPRL) were studied. Using the immunoblotting technique and anti-pPRL antiserum it was shown that the disulfide dimeric form occurred at every stage of pPRL purification. The biological activity of this form was 11.76 +/- 0.59 IU/mg in comparison with the 2nd International standard of ovine PRL when tested in vivo in pigeon cropsac assay. Immunoelectrophoresis with antiserum to the disulfide dimer of pPRL did not reveal any qualitative differences between this form of the hormone, glycosylated and nonmodified variants of pPRL. The potential physiological role of the form of disulfide dimers in the pituitary gland and circulation was discussed. PMID- 2602355 TI - Amiodarone. Therapeutics and guidelines. AB - Amiodarone, a newly marketed Type III antiarrhythmic, is indicated in the treatment of life-threatening ventricular dysrhythmias, including sustained ventricular tachycardia and ventricular fibrillation. Nurses who specialize in the treatment of cardiac patients should familiarize themselves with the general pharmacology of amiodarone. Specifically, nurses should be knowledgable of the considerable side effects of amiodarone and be able to translate to their patients pertinent information about prevention, detection, and management of potential side effects. PMID- 2602356 TI - Nutritional intervention in hyperlipidemia. AB - Sufficient evidence from laboratory, epidemiological, and clinical studies indicates that blood cholesterol level is an important risk factor for coronary heart disease and that lowering elevated blood cholesterol levels can reduce that risk. Hyperlipidemia can be successfully treated in most people by use of individualized, progressive, nutritional intervention strategies. Nurses must be appropriately educated in dietary assessment techniques, nutritional education, and patient counseling in order to implement these strategies effectively. Recent advances in nutritional intervention focus on a series of progressive phases for dietary reduction of fat that interact with variables associated with the individual's characteristics and life-style. Nurses in all settings see patients who require intervention to lower elevated blood cholesterol. Important contributions to therapy can be made by nurses in the areas of screening, patient education, promotion of behavioral change, monitoring dietary change and patient outcomes, and integration of nutritional intervention with other therapies. The nutritional intervention aspect of health promotion is integral to nursing practice. PMID- 2602357 TI - Contiguous gene syndromes due to deletions in the distal short arm of the human X chromosome. AB - Mendelian inherited disorders due to deletions of adjacent genes on a chromosome have been described as "contiguous gene syndromes." Short stature, chondrodysplasia punctata, mental retardation, steroid sulfatase deficiency, and Kallmann syndrome have been found as isolated entities or associated in various combinations in 27 patients with interstitial and terminal deletions involving the distal short arm of the X chromosome. The use of cDNA and genomic probes from the Xp22-pter region allowed us to identify 12 different deletion intervals and to confirm, and further refine, the chromosomal assignment of X-linked recessive chondrodysplasia punctata and Kallmann syndrome genes. A putative pseudoautosomal gene affecting height and an X-linked non-specific mental retardation gene have been tentatively assigned to specific intervals. The deletion panel described is a useful tool for mapping new sequences and orienting chromosome walks in the region. PMID- 2602358 TI - Identification of the binding domain for NADP+ of human glucose-6-phosphate dehydrogenase by sequence analysis of mutants. AB - Human erythrocyte glucose-6-phosphate dehydrogenase is normally quite stable in the presence of 10 microM NADP+. Certain glucose-6-phosphate dehydrogenase variants lose virtually all their activity at this concentration of NADP+ but are reactivated by 200 microM NADP+. Such variants presumably have a defect in their NADP+-binding site. We analyzed the sequence of cDNA or genomic DNA from seven unrelated patients with hemolytic anemia due to the inheritance of variants that are reactivated by NADP+. Six patients had substitutions of one of three adjacent amino acids, and the seventh patient had another amino acid substitution 23 residues downstream. These amino acids are highly conserved, all being present in rat and all but one being found also in Drosophila. The anomalous electrophoretic behavior of some of the variants can be explained by their loss of ability to bind NADP+. We conclude that the region in which these mutations occur defines the binding domain for NADP+ and that binding NADP+ that has been designated as "structural" and as "catalytic" probably occurs at the same site. PMID- 2602359 TI - Increased tumor necrosis factor alpha mRNA after cellular exposure to ionizing radiation. AB - We report that tumor necrosis factor alpha (TNF-alpha) mRNA is increased after treatment with x-rays in certain human sarcoma cells. An increase in TNF-alpha mRNA is accompanied by the increased production of TNF-alpha protein. TNF-alpha enhances radiation lethality in both TNF-alpha-producing and -nonproducing tumor cells. These data suggest that, in addition to the direct cytotoxic effects of x rays, production of TNF-alpha may add to radiation lethality through autocrine and paracrine mechanisms. Combinations of TNF-alpha and therapeutic radiation may be useful in clinical cancer therapy. PMID- 2602360 TI - Abnormal ambient glucose levels inhibit proteoglycan core protein gene expression and reduce proteoglycan accumulation during chondrogenesis: possible mechanism for teratogenic effects of maternal diabetes. AB - Using a tissue culture system based on a nearly pure population of avian precartilage mesenchymal cells, we have found that ambient glucose levels as little as 50% lower, or 100% higher, than normally present in embryonic sera are deleterious to cartilage development, as measured by the accumulation of highly sulfated proteoglycan and the corresponding cartilage-specific chondroitin sulfate core protein mRNA. Abnormal glucose concentrations in the ranges studied did not selectively influence cell replication, and the effects on chondrogenesis were not due to differences in overall protein synthesis or glucose utilization in the treatment groups. Core protein gene expression was more severely affected than accumulation of extracellular product, suggesting the existence of posttranscriptional compensatory mechanisms. The sensitivity to ambient glucose levels of both expression of the cartilage-specific chondroitin sulfate core protein gene and the accumulation of the corresponding extracellular matrix macromolecules during chondrogenesis suggest a molecular mechanism for the well known adverse effect of maternal diabetes on embryonic skeletogenesis. The results further suggest that hypoglycemia resulting from stringent control of diabetes may also be deleterious to skeletal development. PMID- 2602361 TI - The gene SCL is expressed during early hematopoiesis and encodes a differentiation-related DNA-binding motif. AB - We have identified the human gene, SCL. We discovered this gene because of its involvement in a chromosomal translocation associated with the occurrence of a stem cell leukemia manifesting myeloid and lymphoid differentiation capabilities. Here we report the sequence of a cDNA for the normal SCL transcript, as well as for an aberrant fusion transcript produced in the leukemic cells. Although different at their 3' untranslated regions, both cDNAs predict a protein with primary amino acid sequence homology to the previously described amphipathic helix-loop-helix DNA binding and dimerization motif of the Ly1-1, myc, MyoD, immunoglobulin enhancer binding, daughterless, and achaete-scute families of genes. For these cDNAs, at least two different 5' ends are predicted, both of which retain this putative DNA binding domain and predict proteins in the range of 20-30 kDa. SCL mRNA is observed in "early" hematopoietic tissues. Taken together, these studies lead to the speculation that SCL plays a role in differentiation and/or commitment events during hematopoiesis. PMID- 2602362 TI - Isolation, partial amino acid sequence, and immunohistochemical localization of a brain-specific calcium-binding protein. AB - A calcium-binding protein (protein 10) having a molecular mass of 29 kDa and an isoelectric point of 5.3 was purified from guinea pig brain. The amino acid sequence of fragments from proteolytic digestion of protein 10 revealed an 86% sequence identity with a calcium-binding protein (calretinin) found in chicken retina. Polyclonal antibodies against protein 10 revealed a specific distribution of this protein within sensory neurons of auditory, visual, olfactory, nociceptive, and gustatory systems as well as other discrete neuronal circuits in rat and guinea pig brain, whereas no specific label was observed in any of several peripheral tissues examined. PMID- 2602363 TI - Glycyl-L-glutamine opposes the fall in choline acetyltransferase in the denervated superior cervical ganglion of the cat. AB - Intracarotid infusion of 3 microM glycyl-L-glutamine was found to oppose the fall in the choline acetyl-transferase content of the preganglionically denervated cat superior cervical ganglion; this same effect has been demonstrated previously for acetylcholinesterase content. Because choline acetyltransferase, in contrast to acetylcholinesterase, occurs exclusively in the preganglionic axons and their terminals, this finding raises the possibility that glycyl-L-glutamine opposes postsectional axonal degeneration. PMID- 2602364 TI - Cl- permeability of human sweat duct cells monitored with fluorescence-digital imaging microscopy: evidence for reduced plasma membrane Cl- permeability in cystic fibrosis. AB - Salt reabsorption by the human sweat duct is markedly reduced in cystic fibrosis (CF). We used fluorescence-digital imaging microscopy in combination with a halide-specific fluorescent dye [6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ)] to determine if this defective salt reabsorption is referable to a reduced plasma membrane Cl- permeability of the epithelial cells that line the sweat duct. Sweat duct cells were cultured from explants of normal and CF reabsorptive duct and loaded with SPQ, the fluorescence of which is specifically quenched by halide ions (Br- greater than Cl-) and provides a relative index of intracellular halide concentration. Two lines of evidence indicate that normal sweat duct cells exhibit a substantial permeability to Cl- and Br-. First, the replacement of extracellular Cl- with an impermeant anion (i.e., gluconate) resulted in a rapid and reversible increase in the intracellular fluorescence, as expected if the cells rapidly lost Cl- to the extracellular media. Second, the replacement of extracellular Cl- with Br- resulted in a rapid and reversible quenching of the intracellular fluorescence, as expected if the cells accumulated Br- (a more effective quencher of SPQ fluorescence) in exchange for Cl-. The rate of fluorescence change that was induced by either maneuver was inhibited by the Cl- channel blocker, diphenylamine-2-carboxylate (10 microM). Moreover, CF cells exhibited markedly reduced rates of fluorescence change in response to either maneuver. Our results document the utility of this imaging strategy for assessing the Cl- permeabilities of individual epithelial cells that are affected in cystic fibrosis and indicate that the defective salt reabsorption by the CF sweat duct is referable, at least in part, to a reduced plasma membrane Cl- permeability of sweat duct cells. PMID- 2602365 TI - Aggregate-level analysis and prediction of midterm senatorial elections in the United States, 1974-1986. AB - Pattern recognition study demonstrates that the outcomes of American midterm senatorial elections follow the dynamics of simple integral parameters that depict preelectoral situations aggregated to the state as a whole. A set of "commonsense" parameters is identified that is sufficient to predict such elections state-by-state and year-by-year. The analysis rejects many similar commonsense parameters. The existence and nature of integral collective behavior in U.S. elections at the level of the individual states is investigated. Implications for understanding the American electoral process are discussed. PMID- 2602366 TI - Organization of the human lipoprotein lipase gene and evolution of the lipase gene family. AB - The human lipoprotein lipase gene was cloned and characterized. It is composed of 10 exons spanning approximately equal to 30 kilobases. The first exon encodes the 5'-untranslated region, the signal peptide plus the first two amino acids of the mature protein. The next eight exons encode the remaining 446 amino acids, and the tenth exon encodes the long 3'-untranslated region of 1948 nucleotides. The lipoprotein lipase transcription start site and the sequence of the 5'-flanking region were also determined. We compared the organization of genes for lipoprotein lipase, hepatic lipase, pancreatic lipase, and Drosophila yolk protein 1, which are members of a family of related genes. A model for the evolution of the lipase gene family is presented that involves multiple rounds of gene duplication plus exon-shuffling and intron-loss events. PMID- 2602367 TI - Crystallographic refinement of interleukin 1 beta at 2.0 A resolution. AB - The structure of human recombinant interleukin 1 beta (IL-1 beta) has been refined by a restrained least-squares method to a crystallographic R factor of 17.2% to 2.0 A resolution. One-hundred sixty-eight solvent molecules have been located, and isotropic temperature factors for each atom have been refined. The overall structure is composed of 12 beta-strands that can best be described as forming the four triangular faces of a tetrahedron with hydrogen bonding resembling normal antiparallel beta-sheets only at the vertices. The interior of this tetrahedron is filled by hydrophobic side chains. Analysis of sequence alignments with IL-1 beta from other mammalian species shows the interior to be very well conserved with the exterior residues markedly less so. There does not appear to be a clustering of invariant amino acid side chains on the surface of the molecule, suggesting an area of interaction with the IL-1 receptor. Comparison of the IL-1 beta structure with IL-1 alpha sequences indicates that IL 1 alpha probably has a similar overall folding as IL-1 beta but binds to the receptor in a different fashion. The three-dimensional structure of the IL-1 beta is analyzed in light of what has been suggested by previously published work on mutants and fragments of the molecule. PMID- 2602368 TI - Structural basis of protein kinase C activation by tumor promoters. AB - Protein kinase C (PKC) is an important enzyme that helps govern cell metabolism and growth. The enzyme is physiologically activated when an (S)-diglyceride binds to its own regulatory domain. The saturable binding site of the regulatory domain can also be bound by any of a group of structurally diverse tumor promoters, including debromoaplysiatoxins (DATs), phorbol esters, ingenols, teleocidins, and bryostatins. The question of how the same binding site can be the target of these structurally diverse molecules is of considerable importance and is addressed in this article. The relatively rigid structure of DAT and the fact that it possesses a diglyceride moiety renders it an ideal starting template. Structure activity studies with PKC reveal that the C29 but not the C30 stereocenter of DAT is critical for activity. Furthermore, 3-deoxy-DAT and DAT are equipotent as PKC activators, hence the C3 hydroxyl group of DAT is not critical for activity. Straightforward structural considerations show that the C30 hydroxyl group of DAT matches the C3 hydroxyl group of diglyceride, the C29 stereocenter of DAT matches the C2 stereocenter of (S)-diglyceride, and the C1 ester moiety of DAT matches the C2 ester moiety of diglyceride. Based on these studies and on published structure-activity observations on other tumor promoters, a structural hypothesis is developed to account for the chemical mechanism of tumor promoter action. Experimentally testable predictions are made concerning the interactions with PKC of several classes of tumor PKC activators. PMID- 2602369 TI - Echinomycin-induced hypersensitivity to osmium tetroxide of DNA fragments incapable of forming Hoogsteen base pairs. AB - To show conclusively that the critical structural deformation of double-helical DNA that is induced by the binding of quinoxaline antibiotics does not involve the formation of Hoogsteen base pairs, we have prepared a DNA fragment containing the nucleoside analog 7-deaza-2'-deoxyadenosine in one of the two strands. This DNA fragment was subjected to treatment with the thymidine-specific reagent osmium tetroxide and to DNase I "footprinting" in the presence or absence of micromolar concentrations of echinomycin. We report that this anti-tumor antibiotic binds to DNA containing the nucleoside analog as well as to natural DNA and that the previously reported hypersensitivity to osmium tetroxide of certain thymidine residues adjacent to echinomycin binding sites is maintained in analog-containing DNA. Since these thymidines are rendered incapable of participating in Hoogsteen base pairs by the incorporation of 7-deaza-2' deoxyadenosine, we conclude that this unusual base-pairing scheme is not the cause of the observed hypersensitivity to osmium tetroxide and that it therefore results from a large local unwinding of the DNA in the presence of the antibiotic. Moreover, preventing the possibility of Hoogsteen base pairing does not preclude echinomycin binding. PMID- 2602370 TI - Photoregulation of a phytochrome gene promoter from oat transferred into rice by particle bombardment. AB - The regulatory photoreceptor phytochrome controls the transcription of its own phy genes in a negative feedback fashion. We have exploited microprojectile mediated gene transfer to develop a rapid transient expression assay system for the study of DNA sequences involved in the phytochrome-regulated expression of these genes. The 5'-flanking sequence and part of the structural region of an oat phy gene have been fused to a reporter coding sequence (chloramphenicol acetyltransferase, CAT) and introduced into intact darkgrown seedlings by using high-velocity microprojectiles. Expression is assayable in less than 24 hr from bombardment. The introduced oat phy-CAT fusion gene is expressed and down regulated by white light in barley, rice, and oat, whereas no expression is detected in three dicots tested, tobacco, cucumber, and Arabidopsis thaliana. In bombarded rice shoots, red/far-red light-reversible repression of expression of the heterologous oat phy-CAT gene shows that it is regulated by phytochrome in a manner parallel to that of the endogenous rice phy genes. These data indicate that the transduction pathway components and promoter sequences involved in autoregulation of phy expression have been evolutionarily conserved between oat and rice. The experiments show the feasibility of using high-velocity microprojectile-mediated gene transfer for the rapid analysis of light-controlled monocot gene promoters in monocot tissues that until now have been recalcitrant to such studies. PMID- 2602371 TI - Urinary 8-hydroxy-2'-deoxyguanosine as a biological marker of in vivo oxidative DNA damage. AB - DNA is subject to constant oxidative damage from endogenous oxidants. The oxidized DNA is continuously repaired and the oxidized bases are excreted in the urine. A simple routine analytical procedure is described for urinary 8-hydroxy 2'-deoxyguanosine, an oxidative DNA damage adduct, as an indicator of oxidative damage in humans and rodents. This adduct was purified from human urine and characterized. The described assay employs a series of solid-phase extraction steps that separate 8-hydroxy-2'-deoxyguanosine from other urinary constituents, followed by analysis by gradient reversed-phase HPLC coupled to a dual-electrode high-efficiency electrochemical detection system. Analysis of urine from three species by this method indicates that mice excrete approximately 3.3-fold more 8 hydroxy-2'-deoxyguanosine than humans (582 vs. 178 residues per cell per day), a result that supports the proposal that oxidative damage to DNA increases in proportion to species-specific basal metabolic rates. PMID- 2602372 TI - DNA and spermidine provide a switch mechanism to regulate the activity of restriction enzyme Nae I. AB - Sequence-specific DNA-protein interactions are basic to DNA function. To better understand these interactions, we studied the effect of position on cleavage of DNA by the type II restriction enzyme (EC 3.1.21.4) Nae I. We discovered two classes of Nae I restriction sites: sites susceptible and sites resistant to cleavage. Kinetic analysis showed that Nae I was activated by DNA containing cleavable Nae I sites to rapidly cleave resistant Nae I sites by a noncompetitive mechanism with a Km for substrate DNA of about 2 nM and a KA for activating DNA of about 6 nM; activation increased catalysis but not substrate binding. Deletion mutagenesis in vitro showed that sequences flanking the Nae I recognition site were responsible for the differences between activating and nonactivating Nae I sites. The polyamine spermidine had a dramatic effect on the interaction of Nae I with DNA; in the presence of 1 mM spermidine, resistant sites were cleaved rapidly and cleavable DNA inhibited cleavage. The direct regulation of enzymatic activity by DNA sequences in trans, and the modulation of this regulation by a polyamine that is sensitive to the cell cycle, provides a regulatory switch mechanism. The implications of this switch for biological control functions are discussed. PMID- 2602373 TI - A computational approach to the mechanism of self-cleavage of hammerhead RNA. AB - Extensive minimization and dynamics computational studies of the hammerhead structural domain of the virusoid of lucerne transient streak virus have been carried out. The following observations at the self-cleavage position are derived from the resulting three-dimensional structure: (i) the cytosine base is at the surface and does not interact with another base (it is free to move), and (ii) the ribose-phosphate backbone is forced to take an abrupt turn since it bridges stems I and III, and this turn points the pro-S and pro-R oxygens of the phosphate to the inward side of the hammerhead. These structural features are independent of the hammerhead being open or closed and allow an unencumbered 3'- to 2'-endo conformational change of the ribose with the resultant creation of an unusual stereochemistry that allows a direct in-line self-cleavage reaction. In the closed hammerhead structure, interactions of stems I and II create a vacancy into which the catalytic hydrated Mg(II) may be docked on labile phosphate. This opening is not present if stems I and II are shortened. PMID- 2602374 TI - Characterization of the mouse insulin receptor gene promoter. AB - The 5' flanking region of the mouse insulin proreceptor gene was isolated, and the 5' boundary of the minimal promoter was mapped. Genomic clones encompassing greater than 30 kilobases of the gene contain the promoter and exons 1 and 2 interrupted by an approximately 20-kilobase intron at the codon for amino acid 7 of the alpha subunit. The nucleotide sequence of a 1.3-kilobase fragment containing 766 base pairs of the 5' flanking region and the entire first exon was determined. Two major transcription start sites were mapped by S1 nuclease analysis to sites located 469 and 424 nucleotides upstream from the initiation codon for translation. The 5' terminus of an insulin proreceptor cDNA, isolated from a mouse 3T3-L1 adipocyte cDNA library, corresponds to the 3'-most major start site of transcription. The 5' deletion mutants of the 5' flanking region of the proreceptor gene, linked upstream of the bacterial chloramphenicol acetyltransferase reporter gene, were transfected into 3T3-L1 preadipocytes and assayed for promoter activity. The 5' boundary of the minimal promoter, which directs unexpectedly high levels of reporter gene expression, maps to a region 22 base pairs upstream from the 3'-most major transcription start site. PMID- 2602375 TI - Nucleolar targeting signal of human T-cell leukemia virus type I rex-encoded protein is essential for cytoplasmic accumulation of unspliced viral mRNA. AB - The posttranscriptional regulator (rex) of human T-cell leukemia virus type I is known to be located predominantly in the cell nucleolus and to induce the accumulation of gag and env viral mRNAs. The N-terminal 19 amino acids of rex encoded protein (Rex) has been shown to be sufficient to direct hybrid proteins to the cell nucleolus. We have studied the function of the nucleolar targeting signal (NOS) of rex by using full-length proviral DNA and mutant rex expression plasmids. Partial deletions of the NOS sequence abolished the accumulation of unspliced cytoplasmic mRNA, although the gene products of rex mutants were found in the nucleoplasm. These results indicate that NOS sequence, or nucleolar localization of Rex, is essential for Rex function. PMID- 2602376 TI - Three-dimensional ordered distribution of crystals in turkey tendon collagen fibers. AB - The organization of apatite crystals and collagen fibrils in mineralized turkey tendon has been studied by electron microscopy and electron diffraction. To minimize artifactual distortions the tissue was examined, for the first time, as isolated fibrils in an aqueous environment of vitreous ice, as well as in conventionally prepared sections. The electron micrographs show that the plate shaped apatite crystals are arranged in parallel arrays across the collagen fibrils. This provides direct evidence for highly asymmetric assembly in collagen fibrils, and, indeed, the fibrils were observed to be elongated rather than round in cross-section. There is, furthermore, a pronounced tendency for the layers of crystals to be coherently aligned in adjacent fibrils. These observations may also be important for understanding the mechanical behavior of bone at the molecular level, as such extended, aligned aggregates of flat crystals could develop into natural fracture planes in mature bone. PMID- 2602377 TI - Fourier transform infrared evidence for proline structural changes during the bacteriorhodopsin photocycle. AB - Structural changes involving bacteriohodopsin proline residues have been investigated by Fourier transform infrared difference spectroscopy. Bacteriohodopsin (bR)-producing Halobacteria halobium were grown on a stringent medium containing either ring-perdeuterated proline or 15N-labeled proline. Comparison of the difference spectra obtained from the photoreactions of these labeled bR samples with those for unlabeled bR has led to the assignment of peaks due to proline vibrations. [proline-N15]bR exhibited a 15-cm-1 isotopic downshift of peaks in the 1420- to 1440-cm-1 region of the bR----K and bR----M difference spectra as well as a similar downshift of peaks found in the absolute absorption spectrum of bR. In contrast, [proline-D7]bR did not cause shifts in this region of the difference spectra. These results indicate that one or more prolines undergo a structural rearrangement during the bR photocycle involving the Xaa-Pro C--N peptide bond. This change may be directly coupled to the light-induced isomerization of the retinal chromophore from all-trans-retinal to 13-cis retinal. PMID- 2602378 TI - Predictions of structural elements for the binding of Hin recombinase with the hix site of DNA. AB - Molecular dynamics simulations were coupled with experimental data from biochemistry and genetics to generate a theoretical structure for the binding domain of Hin recombinase complexed with the hix site of DNA. The theoretical model explains the observed sequence specificity of Hin recombinase and leads to a number of testable predictions concerning altered sequence selectivity for various mutants of protein and DNA. PMID- 2602379 TI - Expression of proteinase inhibitors I and II in transgenic tobacco plants: effects on natural defense against Manduca sexta larvae. AB - Genes containing the cauliflower mosaic virus 35S promoter fused to open reading frames coding for tomato proteinase inhibitor I, tomato inhibitor II, and potato inhibitor II were expressed in transgenic tobacco plants. Inhibitor I and II proteins were identified by immunoblotting and quantified by immunoradial diffusion. Both inhibitors exhibited the molecular weights found for the native proteins in their natural environments. Extracts of leaves from transformed plants contained inhibitory activities against trypsin and chymotrypsin that reflected the levels of inhibitor I or II protein present. The results demonstrate that in tobacco leaves the introns of both inhibitor I and inhibitor II genes were excised correctly and that pre and prepro inhibitor I and II proteins were correctly processed. Growth of Manduca sexta larvae (tobacco hornworms) feeding on leaves of transgenic plants containing inhibitor II, a powerful inhibitor of both trypsin and chymotrypsin, was significantly retarded, compared to growth of larvae fed untransformed leaves. Levels of inhibitor II protein as low as 50 micrograms/g of tissue moderately affected larval growth, whereas levels above 100 micrograms/g severely reduced growth. The presence of tomato inhibitor I protein, a potent inhibitor of chymotrypsin but a weak inhibitor of trypsin, in transgenic tobacco leaves had little effect on the growth of the larvae. These experiments indicated that trypsin inhibitory activity, but not chymotrypsin inhibitory activity, was mainly responsible for the inhibition of larval growth. PMID- 2602380 TI - Cellular responses to Ca2+ from extracellular and intracellular sources are different as shown by simultaneous measurements of cytosolic Ca2+ and secretion from bovine chromaffin cells. AB - Bovine adrenal medullary cells, cultured on quartz plates, were superfused with buffer to which pulses of stimulant were added. Cytosolic Ca2+ was measured by the fura-2 fluorescence method and the simultaneously released catecholamine was measured electrochemically. When stimulant concentrations were adjusted to given equivalent elevations of cytosolic Ca2+, secretion depended entirely on whether Ca2+ came from internal stores or from the extracellular medium. Calcium from internal stores did not support secretion under these conditions. This nonequivalence of the two sources of cytosolic Ca2+ points to important differences in the physiological roles of the two sources of calcium. Dimethylphenylpiperazinium (a cholinergic agonist) and elevated K+ increased cytosolic Ca2+ and caused secretion only in the presence of external Ca2+. Bradykinin, muscarine, and ATP elevated cytosolic Ca2+ in the presence and absence of extracellular Ca2+ but caused secretion only in the presence of extracellular Ca2+. UTP, which in the absence of extracellular Ca2+ elevated cytosolic Ca2+ as effectively as ATP, did not cause detectable secretion under any circumstance. Because of the high Ca2+-buffering capacity of the cytosol, we expected that Ca2+ gradients, perhaps quite steep, would be produced by a pulse of Ca2+ entering the cytosol. Fura-2 fluorescence measures only the average free cytosolic Ca2+. Our data show that Ca2+ entering across the plasma membrane was much more effective at triggering exocytosis than was Ca2+ released from internal stores, suggesting that the two sources of Ca2+ are effectively compartmentalized, probably by concentration gradients in the cytosol. PMID- 2602382 TI - Phosphatidylserine translocation to the mitochondrion is an ATP-dependent process in permeabilized animal cells. AB - Chinese hamster ovary (CHO-K1) cells were pulse labeled with [3H]serine, and the synthesis of phosphatidyl[3H]ethanolamine from phosphatidyl[3H]serine during the subsequent chase was used as a measure of lipid translocation to the mitochondria. When the CHO-K1 cells were pulse labeled and subsequently permeabilized with 50 micrograms of saponin per ml, there was no significant turnover of nascent phosphatidyl[3H]serine to form phosphatidyl[3H]ethanolamine during an ensuing chase. Saponin treatment rendered greater than 99% of the cells permeable as judged by trypan blue exclusion and depleted them of 85% of their complement of cytosolic proteins as determined by residual lactic acid dehydrogenase activity. Supplementation of the permeabilized cells with 2 mM ATP resulted in significant phosphatidyl[3H]ethanolamine synthesis (83% of that found in intact cells) from phosphatidyl[3H]serine during a subsequent 2-hr chase. Phosphatidyl[3H]ethanolamine synthesis essentially ceased after 2 hr in the permeabilized cells. The translocation-dependent synthesis of phosphatidyl[3H]ethanolamine was a saturable process with respect to ATP concentration in permeabilized cells. The conversion of phosphatidyl[3H]serine to phosphatidyl[3H]ethanolamine did not occur in saponin-treated cultures supplemented with 2 mM AMP, 2 mM 5'-adenylyl imidodiphosphate, or apyrase (2.5 units/ml) plus 2 mM ATP. ATP was the most effective nucleotide, but the addition of GTP, CTP, UTP, and ADP also supported the translocation-dependent synthesis of phosphatidyl[3H]ethanolamine albeit to a lesser extent. These data provide evidence that the interorganelle translocation of phosphatidylserine requires ATP and is largely independent of soluble cytosolic proteins. PMID- 2602381 TI - MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. AB - The MUC18 antigen is an integral membrane glycoprotein of 113 kDa whose expression on primary human melanomas correlates with poor prognosis and the development of metastatic disease. MUC18 is expressed only sporadically in benign melanocytic nevi and thin primary melanomas that have a low probability of metastasizing. However, with increasing tumor thickness, MUC18 expression becomes more frequent and it is found on 80% of advanced primary tumors and metastases. MUC18-encoding cDNA clones were obtained by screening a human melanoma phage lambda expression library with monoclonal antibodies produced against the denatured antigen. The deduced sequence of 603 amino acids consists of a signal peptide, five immunoglobulin-like domains, a transmembrane region, and a short cytoplasmic tail. The highest sequence similarity is with a group of nervous system cell adhesion molecules, which includes neural cell adhesion molecule (N CAM). The close structural relationship with these molecules suggests that MUC18 may also be a developmentally regulated cell adhesion molecule. PMID- 2602383 TI - Visualization of crystallin droplets associated with cold cataract formation in young intact rat lens. AB - The structure, distribution, and nature of scattering elements associated with cold cataract formation in the young rat lens were studied in situ using light and electron microscopy and ImmunoGold electron microscopy. A large accumulation of spherical droplets, ranging from approximately 1.5 microns to 10 microns in diameter, were found in the lens nucleus in cold cataracts induced at 22 degrees C or 4 degrees C in TC-199 culture medium. Many droplets of all sizes were associated with the cell membranes. A cooled and then rewarmed lens was found to lose its opacity and subsequently no droplets were observed, indicating that there was a good correlation between the onset of opacification and the formation of droplets. Electron microscopy showed that droplets were composed of homogeneous electron-dense aggregates without limiting membranes. ImmunoGold study revealed that alpha-, beta-, and gamma-crystallins were all present within each droplet. This study demonstrates that extensive accumulation of the crystallin droplets in the lens nucleus is the contributing factor for the light scattering and opacification of the cold cataract in the young intact rat lens. PMID- 2602384 TI - Reconstitution of translocation-competent membrane vesicles from detergent solubilized dog pancreas rough microsomes. AB - Dog pancreas rough microsomes were solubilized in 1% octyl beta-glucoside, and membrane vesicles were reconstituted by slow 30-fold dilution with a buffer of low ionic strength. Asymmetric assembly of the membranes occurred during reconstitution since the vesicles formed contained ribosomes bound only to the vesicular outer surfaces. The reconstituted vesicles were similar in protein composition to native rough microsomes, although these vesicles were largely devoid of luminal-content proteins. These reconstituted vesicles could translocate and process nascent secretory (human placental lactogen) and membrane proteins (influenza hemagglutinin and rat liver ribophorin I) synthesized in cell free translation systems programmed with the corresponding mRNAs. Signal cleavage and N-glycosylation only occurred when the reconstituted membranes were present during translation, providing evidence that the translocation apparatus was asymmetrically assembled into the reconstituted membranes. When a supernatant lacking ribosomes and particles greater than 50S from centrifuging the detergent solubilized microsomes at high speed was used for reconstitution, smooth-surfaced membrane vesicles were obtained that, except for the absence of ribosomal proteins, were similar in protein composition to that of the reconstituted vesicles from total solubilized rough microsomes. The reconstituted smooth surfaced vesicles, however, were totally inactive in cotranslational processing and translocation of nascent polypeptides. These findings suggest that ribosomes and/or large macromolecular complexes, not dissociated under our solubilization conditions, are essential for in vitro assembly of a functional translocation apparatus. PMID- 2602385 TI - Host species-specific conservation of a family of repeated DNA sequences in the genome of a fungal plant pathogen. AB - We have identified a family of dispersed repetitive DNA sequences in the genome of Magnaporthe grisea, the fungus that causes rice blast disease. We have named this family of DNA sequences "MGR" for M. grisea repeat. Analysis of five MGR clones demonstrates that MGR sequences are highly polymorphic. The segregation of MGR sequences in genetic crosses and hybridization of MGR probes to separated, chromosome-size DNA molecules of M. grisea shows that this family of sequences is distributed among the M. grisea chromosomes. MGR sequences also hybridize to discrete poly(A)+ RNAs. Southern blot analysis using a MGR probe can distinguish rice pathogens from various sources. However, MGR sequences are not highly conserved in the genomes of M. grisea field isolates that do not infect rice. These results suggest that host selection for a specific pathogen genotype has occurred during the breeding and cultivation of rice. PMID- 2602387 TI - Estrogen stimulates both prolactin and growth hormone mRNAs expression in the MtT/F4 transplantable pituitary tumor. AB - The effects of 17 beta-estradiol (E2) on MtT/F4 pituitary tumor growth and on prolactin (PRL) and growth hormone mRNA expression were analyzed in F344 female rats. E2 (10 mg) stimulated pituitary PRL cell hyperplasia and PRL mRNA, but inhibited growth of the transplantable tumors. The expression of both PRL and growth hormone mRNA levels was increased in the MtT/F4 tumors. The effects of E2 on increasing PRL mRNA levels were more marked in the pituitary compared with the tumors. These results indicate that estrogens stimulate proliferation and PRL expression in the pituitary while inhibiting cell proliferation in the MtT/F4 tumor. E2 also stimulated both growth hormone and PRL mRNA expression in the MtT/F4 transplantable tumor. PMID- 2602386 TI - I/Lyn mouse phosphorylase kinase deficiency: mutation disrupts expression of the alpha/alpha'-subunit mRNAs. AB - A cDNA encoding the alpha subunit of mouse skeletal muscle phosphorylase kinase was used to compare the expression of alpha mRNAs in normal and phosphorylase kinase-deficient tissues of the I/Lyn mouse. The results demonstrate that two different molecular weight species of poly(A)+ RNA in normal mouse heart and skeletal muscle hybridize to the alpha cDNA. These two mRNAs direct the synthesis of alpha protein and its isoform alpha' in a cell-free translation system. Thus, alpha and alpha' are encoded by two distinct mRNAs. The abundance of both of these mRNAs is reduced dramatically in the phosphorylase kinase-deficient skeletal muscle and heart tissues from the I/Lyn mouse strain. This result indicates that a mechanism common to both alpha and alpha' expression is disrupted by the I/Lyn mutation. The I/Lyn deficiency is inherited as an X chromosome trait. By Southern mapping of Chinese hamster-mouse cell hybrids the alpha gene was localized to the mouse X chromosome, supporting the possibility that the I/Lyn mutation is in the alpha gene. These results are discussed in terms of a cis or trans mutation influencing the expression of either a single alpha/alpha' gene or two genes encoding alpha and alpha'. PMID- 2602389 TI - Renal sympathetic nerve activity and arterial pressure responses to changes in postural position of conscious dogs. AB - Experiments were conducted in conscious dogs to determine the relationships between postural position, arterial pressure, and renal sympathetic nerve activity. Observations of the changes in arterial pressure and renal nerve activity were made when animals spontaneously changed postural position from lying to sitting, sitting to standing, standing to sitting, and sitting to lying. Rising to sit from lying down increased arterial pressure from 109 +/- 5 to 125 +/- 3 mm Hg and increased renal nerve activity by 96 +/- 58 microV/sec (61% of control). Movement from the sitting to standing position decreased renal nerve activity by 90 +/- 39 microV/sec (48% of control) without changing mean arterial pressure. Sitting down from standing also did not change arterial pressure, whereas renal nerve activity increased by 56 +/- 17 microV/sec (33% of control). Returning to the lying position (from sitting) decreased arterial pressure, and this hypotension was associated with significant reductions in renal nerve activity. These results indicate that nonuniform changes in sympathetic outflow from the central nervous system must occur to various vascular beds during changes in postural position of conscious dogs. Thus, renal sympathetic outflow may or may not reflect changes in nerve traffic which contribute to alterations in arterial pressure. PMID- 2602388 TI - Behavioral endocrinology of male rats with periodic sexual contacts with exclusive or varied females. AB - Sexual contact keys a profound series of acute and chronic changes in males that, presumably, are orchestrated by acute pulsatile release of hormones. An experimental paradigm is reported in which male rats were paired periodically with either the same or different estrous females to receive identical amounts of copulatory experiences. Results confirmed the hypothesis that exposure to an unfamiliar female would induce a different endocrine response which would be reflected in various androgen-sensitive systems. The "successively polygynous" males showed more sexual behavior than "monogamous" males, and their respective females solicited the males differently, as well. Circulating levels of testosterone were higher immediately after sexual contact with an unfamiliar than with a familiar female partner. There were no differences in testosterone titers among the groups when the animals were killed at either 2 or 7 weeks after the final copulatory experiences. Yet, necropsies at 2 weeks postcopulation revealed that primary and secondary sex structures from polygynous males clearly were larger. Differences between the two experimental groups were reduced after 7 weeks of sexual rest, yet, polygnous males continued to show a different structural profile than the other groups. Conclusions were that males may experience greater activation of androgen-sensitive behavior and physiology following qualitatively different sexual contacts. PMID- 2602390 TI - Determination of Kupffer cell Fc receptor function in vivo following injury. AB - This study was carried out to determine whether Kupffer cell Fc receptor function is depressed after injury. Three approaches to the determination of Fc receptor function were evaluated: IgG-coated erythrocytes (EIgG) were used as the receptor probe with a perfused liver system, EIgG were used as the receptor probe in vivo, and small aggregates of IgG (AIgG) were used as the receptor probe in vivo. Nearly half of the injected dose of EIgG was taken up by the perfused liver (nonrecirculating, serum-free system). In contrast, only 2.6% of erythrocytes not coated with IgG were taken up, and only 5.6% of erythrocytes coated with IgM were taken up by the perfused liver. Thus, there was little nonspecific or complement dependent uptake of EIgG by the liver. The uptake of EIgG by the perfused liver was depressed following thermal injury, endotoxemia, and the phagocytosis of EIgG. These results were interpreted as indicating that Kupffer cell Fc receptor function was depressed under these conditions. The results obtained with the hepatic uptake of EIgG in vivo were very similar to those with EIgG in the perfused liver. However, since it was found that complement receptors as well as Fc receptors were probably involved in the in vivo clearance of EIgG, these results could be due to a depression of one or both of these receptors. The hepatic uptake of AIgG was not depressed by complement depletion, but was decreased by the injection of large aggregates of IgG. However, the hepatic uptake of AIgG was not depressed following thermal injury, endotoxemia, or the phagocytosis of EIgG. Thus, AIgG was not sensitive to the effects of injury on Kupffer cell function, whereas the uptake of EIgG by the perfused liver may provide an indication of Kupffer cell Fc receptor function. The depression of Kupffer cell Fc receptor function following injury may contribute to the impairment of host defense caused by injury. PMID- 2602391 TI - Thrombolysis using liposomal-encapsulated streptokinase: an in vitro study. AB - The clot-lysing ability of streptokinase (SK) was examined using membrane-bound thrombi. Encapsulation of SK in large unilamellar phospholipid vesicles (liposomes) resulted in entrapping approximately 30% of its original activity. Measurements of streptokinase activity for liposomal-encapsulated streptokinase (LESK) indicated little loss of activity or leakage in Tris-buffered saline over a 24-hr period at temperatures of 4 and 23 degrees C. However, incubation of free SK and LESK in platelet-poor plasma (PPP) at 37 degrees C resulted in a decrease of SK activity. The retention of SK activity in LESK was considerably higher than that of unentrapped SK. Clot-dissolving time (CDT) was measured by monitoring the pressure drop during slow filtration in plasma through membrane-bound thrombi. The results indicated that both LESK and free SK were able to activate the fibrinolytic system. Without prior incubation in PPP at 37 degrees C, the CDT of a SK and PPP mixture (SK/PPP) was 10.7 +/- 1.9 min (n = 12), while that of a LESK and PPP mixture (LESK/PPP) was 12.4 +/- 1.7 min (n = 12). The CDT-detected clot lysing abilities of both SK and LESK were diminished by incubation in PPP, but to different extents. After 15- and 30-min incubations, the CDT of SK/PPP increased significantly to 15.5 +/- 1.5 and 24.1 +/- 2.4 min (n = 5, P less than 0.05), respectively. In contrast, the CDT of LESK/PPP increased to 13.3 +/- 0.8 min (n = 5) after 15 min of incubation and to 16.0 +/- 1.1 min (n = 5, P less than 0.05) after a 30-min incubation. These results suggest that entrapment of SK in liposomes preserves the thrombolytic potential of the plasminogen activator by limiting its exposure to the components of the plasma. PMID- 2602392 TI - Effects of malonate administration on renal ammoniagenesis in intact dogs. AB - In the dog kidney in vivo, malonate augmented ammoniagenesis from both amide and nonamide nitrogen sources, similar to previous in vitro investigations using incubating canine renal tubules. This was highly significant in alkalotic dogs, where it was accompanied by decreased renal tissue concentrations of glutamate. Changes in renal ammonia metabolism were less evident in acidotic dogs where a markedly decreased glomerular filtration rate was noted following malonate administration. Under conditions of complete ureteric obstruction which effectively abolished glomerular filtration, malonate significantly augmented ammoniagenesis above baseline in acidotic dogs. These in vivo results with malonate have similarities to those seen in dogs subjected to an acid challenge alone and suggest that the adaptation in renal ammoniagenesis under both circumstances occurs via enhanced deamination of glutamate pools. PMID- 2602393 TI - Urate excretion by the isolated perfused rat kidney and modification by drugs. AB - Urate excretion in the isolated perfused rat kidney was studied over a wide range of perfusate urate concentrations (13.9-376.8 microM). Fractional excretion of urate (FEurate) averaged 57.9 +/- 2.0% (range, 58.5-59.6%), showed marked interanimal variability, but was not dependent on the perfusate-free urate concentration. In paired experiments, the effects of five drugs (probenecid, pyrazinoate, furosemide, salicylate, and oxonate) on FEurate were evaluated. A low concentration of pyrazinoate (0.2 mM) decreased FEurate (62.0 +/- 1.9 vs 53.8 +/- 2.4%, P less than 0.05), as did 0.8 mM pyrazinoate (59.5 +/- 2.4 vs 48.4 +/- 2.7%, P less than 0.05). Probenecid (1 mM) decreased FEurate (59.3 +/- 3.1 vs 52.0 +/- 2.5%, P less than 0.05) but 2.5 mM probenecid did not alter FEurate (48.0 +/- 6.3 vs 47.8 +/- 6.9%). Oxonate (0.1 mM) also decreased FEurate (75.8 +/ 4.2 vs 67.1 +/- 2.1%, P less than 0.05) while 0.2 mM oxonate had no effect (66.4 +/- 3.5 vs 61.5 +/- 4.6%). Neither salicylate nor furosemide affected FEurate, although both drugs caused a saliuresis and diuresis. Thus, urate transport in rat kidneys in vitro is not dependent on urate concentration, unlike man. Some drugs known to affect urate excretion in humans and rats did not have similar effects in isolated kidneys. Isolated organ studies provide additional information is understanding renal urate handling. PMID- 2602395 TI - A training marketplace. PMID- 2602394 TI - Dihydrotestosterone secretion in pregnant and pseudopregnant rats. AB - The objective of this study was to determine levels of dihydrotestosterone in the peripheral circulation and the source of its secretion throughout pregnancy and pseudopregnancy. Rats were bled from the jugular vein and ovarian or uterine vein from Day 8 through Day 22 of pregnancy and from Day 8 through the end of pseudopregnancy in various types of pseudopregnant rats. Jugular vein samples alone were obtained on the day of parturition and every fourth day thereafter during the lactational period. Our results indicate that the levels of dihydrotestosterone in the peripheral circulation were high throughout pregnancy and pseudopregnancy then declined during the lactational period. The sources of dihydrotestosterone were primarily the ovary in pseudopregnant rats and the ovary plus uterus in pregnant rats. PMID- 2602396 TI - 2000 plus: the new nursing. AB - Project 2000 has opened up the possibility of a new nursing - a more independent and confident profession. However, if this is to succeed, every registered nurse must embrace the idea of change. If this does not happen, the Project cannot hope to cure the profession's ills. PMID- 2602397 TI - A responsive service: health education for Asians with diabetes. AB - Services for people with diabetes are generally set up to cater for the 'average' client. As our society becomes more multiracial, it is vital to set up new services which cater for ethnic minorities. PMID- 2602398 TI - Pressure sore management: the patient's role. AB - Patient education can lead to better healing of pressure sores, but it is essential that education programmes are tailored to the needs of the individual. PMID- 2602399 TI - Weaning--a first step to independence. AB - There are no hard and fast rules when it comes to weaning babies, but it can be an emotional time for both parents and child. The information given by health professionals can have a radical effect on the success of this stage. PMID- 2602400 TI - The sooner the better! Teaching continence promotion to women. PMID- 2602401 TI - AIDS--the rights approach. AB - When confronted by Aids, nurses may react in different ways, but they must always keep the rights of the individual sacrosanct. This article illustrates how individual rights may be ignored simply because people have become entangled in the Aids issue. PMID- 2602402 TI - Infusion phlebitis and extravasation. PMID- 2602403 TI - Are you sitting comfortably? Good seating requirements in a patient care setting. AB - The provision of seating in the wards is something we all take for granted. However, poor seating design can exacerbate patient injury and illness, and so require extra nursing time. PMID- 2602404 TI - Involvement of the central nervous system and its coverings in different forms of amyloidosis. AB - The list of human amyloidoses contains at least ten different types that might be differentiated on account of their pattern of distribution (localized or generalized), on the basis of their underlying diseases and above all on account of their different amyloidogenic proteins. According to WRIGHT it was already possible to differentiate two types of amyloid by pretreating the histologic tissue sections with KMnO4 before staining them with Congored. But now nearly all different types of amyloid can be determined immunohistologically by means of specific antibodies. In the human brain and in its coverings we found as well localized as generalized amyloidoses. The most frequent localized amyloidosis is the cerebral amyloidosis in Alzheimer's disease, in senile dementia of the Alzheimer type and in "normal" aging (type ASb). The endocrine type of amyloid could be detected in the anterior pituitary lobe of old people and sometimes in adenomas of the pituitary gland (type AE). In cases of generalized amyloidosis (e.g. amyloid type AA, type AF or type AL) the intracranial amyloid deposits or precipitations are only found in those regions where the blood brain barrier is insufficient. These regions are --choroid plexus --infundibulum (hypothalamus) - pineal gland (epiphysis) --area postrema --circumventricular organs --ganglion Gasseri and --dura mater. The other parts of the CNS (the leptomeninges, cortical grey matter, subcortical white matter and basal ganglia) are always free of amyloid in these cases of generalized amyloidosis. In cases of cerebral amyloidosis (type ASb) the typical berefringent Congored deposits are found in the leptomeninges and in cortical and subcortical grey matter; white matter and all other regions are always free of amyloid. We observed several cases with more than one type of amyloidosis: e.g. a generalized form and a second local amyloidosis, two generalized forms (AA and A beta 2M) or even several localized types (ASb, AE). By paying attention to the typical distribution pattern of the amyloid deposits in the CNS and its coverings and by using specific antibodies it is now possible to distinguish between two different amyloidoses even in the same body region, e.g. in the human brain. PMID- 2602405 TI - ICP-MS: a new look at trace elements in Alzheimer's disease. AB - It has been known for over 100 years that trace elements play an essential role in metabolism. Some 24 elements are now acknowledged as being essential to life. Many conditions have been examined in recent years from a trace element viewpoint. Alzheimer's disease and the part played by aluminium has received much attention, particularly since Crapper's work in the early 1970's. Extremely low levels of elements of interest and inappropriate methods of analysis are problems common to elemental tissue studies. Many early studies are now known to have reported falsely high levels of elements in tissues for just these reasons. Much research in recent years has been directed to looking at a range of trace elements thought to play a part in neurological disorders, particularly Alzheimer's disease. Inductively Coupled Plasma Source Mass Spectrometry (ICP-MS) is an ultra-sensitive, multi-element technique which can determine up to 90% of the elements in the periodic table, many at the sub ng.g-1 level. Developed and adopted commercially within the last 10 years, ICP-MS has to date been applied mainly to geological and environmental studies. Its suitability for use in biological investigations is now being exploited to examine the levels of 20 elements in brain tissue, cerebrospinal fluid, serum and aqueous humour from Alzheimer victims and matched control subjects. PMID- 2602406 TI - Hair aluminium in normal aged and senile dementia of Alzheimer type. AB - To investigate relationship between aluminium and senile dementia of Alzheimer type (SDAT), hair aluminium concentration was measured by ICP method in 35 cases of SDAT (mean 80 yr.) diagnosed clinically and 71 normal aged volunteers (mean 76 yr.). In normal aged, cerebral blood flow (CBF) also determined by Xe133 inhalation method simultaneously. Mean hair aluminium concentration in SDAT was within normal range of Japanese subjects and significantly lower than that of normal aged controls. There was no significant aging effect to hair aluminium concentration in both groups. Hair calcium and magnesium concentrations were significantly lower in SDAT than that of normal aged. Hair aluminium positively correlated to hair calcium and magnesium in SDAT. Hair aluminium negatively correlated to CBF, and CBF positively correlated to calcium and magnesium concentrations in hair in normal aged. Hair aluminium concentration does not appear to be of use in the diagnosis of SDAT. However, it is undeniable that decreased calcium and magnesium enhance selective accumulation of aluminium in the brain in SDAT. Inverse correlation between hair aluminium and CBF in normal aged suggests that aluminium might have some contribution to aging of the brain. PMID- 2602407 TI - Regional stimulation of cholinergic function by nerve growth factor in an animal model of Alzheimer's disease. PMID- 2602408 TI - Cholinesterase inhibitor therapy for Alzheimer dementia: what do animal models tell us? AB - Despite a strong rationale for the use of cholinesterase (ChE) inhibitors and related drugs to augment cholinergic function as palliative treatment for Alzheimer dementia, this approach met with limited and variable success until the striking results recently reported with tacrine (THA). Our previous studies have shown the potential utility of blood ChE inhibition to define the optimum dose of such drugs. In the present studies, THA was reinvestigated in rats because several literature reports of weak inhibition of blood and brain acetylcholinesterase (AChE) after systemic treatment leave unresolved the mechanism of action for THA. Consistent with previous reports, we find an in vitro IC50 of 1 microM THA or less for brain or red blood cell AChE, dependent on the substrate concentration. Results were independent of tissue dilution in vitro. However, after in vivo THA, the inhibition of plasma ChE or brain AChE declined as a log function of tissue dilution. These results indicate that the degree of inhibition is underestimated as a result of dilution of tissue for enzyme assay. We therefore used minimal tissue dilution to establish the dose response and time course functions after s.c. administration of THA and to compare the effect of THA in various brain regions with that on blood enzymes. Pons-medulla AChE was much less sensitive to the effects of THA than hippocampus, cortex, cerebellum or plasma ChE, particularly at doses of 2.5 mg/kg or less. In these other brain regions, AChE was inhibited 22-44% after doses of 1.25 to 2.5 mg/kg THA, the dose range which maximally improved retention performance in mice. Peak inhibition occurred rapidly in plasma, but was delayed in brain (30-60 min after THA). Inhibition was long-lasting in both plasma and cortex (greater than or equal to 5 hr). It is concluded that long-lasting inhibition of the metabolism of acetylcholine is the most heuristic explanation of THA's pharmacological activity. PMID- 2602409 TI - Diffuse Lewy body disease: an important differential diagnosis in dementia with extrapyramidal features. AB - Fifteen cases of diffuse Lewy body disease were identified in a systematic survey of all 216 brains referred to this hospital from a single health district in a single year. These cases presented with Parkinson's disease (40%), cognitive impairment (40%) and both (20%). Quantitative neuropathological studies using anti-ubiquitin immunocytochemistry revealed that dementia severity was related to cortical Lewy body density. The prevalence of diffuse Lewy body disease may have been underestimated in the past because of the neuropathological difficulties in making the diagnosis. Firstly, cortical Lewy bodies have a subtle appearance and are easy to overlook. Secondly, senile plaques are a common feature of diffuse Lewy body disease and may lead the unwary to make an erroneous diagnosis of Alzheimer's disease or "plaque-only Alzheimer's disease'. Diffuse Lewy body disease is a common and important cause of parkinsonian dementia, including the dementia of Parkinson's disease itself. PMID- 2602410 TI - A natural and broad spectrum nootropic substance for treatment of SDAT--the Ginkgo biloba extract. AB - The efficacy of the Ginkgo biloba extract was not only found clinically or in standardised ratings but also documented by objective data, obtained by a computerized EEG method, the DYNAMIC BRAIN MAPPING and BRAIN FUNCTION MONITORING SYSTEM (Dr. T. Itil, New York). A one year open trial comprise 25 parkinson patients with additional signs of SDAT. Data from 3 selected cases were given: The short time efficacy of the substance after the infusion and the long-term result after the oral medication. The maps showed less slower and more faster waves. Without any side effects the Ginkgo biloba extract seems to be a substance with a broad spectrum of influence. Our therapeutic findings in parkinsonian patients with SDAT and the data taken from healthy elderly volunteers revealed that the computerized EEG method may have another big advantage: It seems that the so-called anteriorisation of the Theta waves can be taken as a preclinical sign of an incipient change in brain metabolism. As a consequence--it might be that these changes are reversible by an adequate nootropic treatment. Further studies and treatment experiences must confirm these preliminary findings. PMID- 2602412 TI - Methodological concerns: evaluating central nervous system (CNS) active compounds in Alzheimer's disease (AD). PMID- 2602411 TI - National Alzheimer's disease program. AB - The psycho-behavioral troubles of patients with an Alzheimer's Disease (AD) are such that it is very difficult to keep those patients within the normal family environment, and that it therefore proves necessary to have them placed in a specially adapted residence manned by a highly specialised medical and para medical staff. Within the frame of such an approach, a new type of residence has been devised "Asclepios Gardens", a one-level ranch-type residence, including 44 individual apartments, each opening, on the one hand, on a little private garden opening itself on a large, strictly enclosed and protected, 5-acre park, and, on the other hand, on a collective living structure conceived for social activities under attentive medical care, to help the patients restore their social structures. In a such residences, besides the special training given to the staff (medical, para-medical), aimed at developing as much as possible the patients' autonomy and self-reliance in every aspect of everyday life, you find a psychometric computerized "activation" program, devised both on a collective basis with differentiated subprograms, for groups of patients that have been classified according to the degree of seriousness of their problem, and-whenever possible, with individual attention programs; the whole of this "activation" method has thus clearly a double target; first to develop what is left of the patients' autonomy, for instance by psychometric exercises, and moreover, to have them start new activities, which they had never practised before--this latter action with a view to developing their neuroplasticity resources. And finally, a new chemical therapy is proposed. This substance induced a significant improvement in 40% of cases and a slight improvement in 20%. These results were observed through a series of specific psychometric tests (Visuo Retention Test of Benton, Mnesic profile of Rey), a global scale (Mini Mental State), and a general evaluation of the patients' daily activities by the General Practitioner and by the family. These preliminary data very interesting yet must be confirmed in a larger Alzheimer population. PMID- 2602413 TI - Dementia in hereditary cystatin C amyloidosis. AB - Nineteen cases with verified Hereditary Cystatin C Amyloid Angiopathy are presented. All of the cases had one or more cerebrovascular insults starting at the age of 20-41 years and survived from 10 days to 23 years after the first insult. Progressive dementia was a prominent clinical feature in seventeen cases of whom two presented with dementia. At the last examination the majority had severe dementia and severely abnormal EEG. Anti-cystatin C positive amyloid vascular and perivascular infiltrates were found. The resulting damage to the microvasculature of the brain and secondary hemorrhages and infarctions were considered to be an adequate explanation for the dementia in these cases. Skin biopsies can now probably be used to demonstrate cystatin C positive amyloid deposits conclusively in the tissues of these patients. PMID- 2602414 TI - Neuropsychological characteristics of subjects with and without neocortical Alz 50 immunoreactivity. AB - We performed quantitative histopathology and Alz-50 staining on 8 non-demented and 16 demented subjects who had received yearly neuropsychological evaluations as part of prospective studies of dementia. Of the 8 non-demented subjects, four had begun to show signs of cognitive decline on serial neuropsychological testing. These subjects showed marked decline on the Fuld Object Memory Evaluation, a test of recent memory. Scores on IQ tests and the Blessed test of orientation, memory, and concentration showed fluctuations but not consistent declines. These old-old, retired subjects were called "cognitively impaired" but not demented because they did not show decline in activities of daily living or social interactions. Five of the non-demented subjects had numerous cortical senile plaques and met standard pathological criteria for Alzheimer's disease (AD), but only one of the five was Alz-50 positive. That subject had shown the most consistent decline on neuropsychological scores. Ten of 11 clinically demented subjects with pathological evidence of AD were Alz-50 positive. All five clinically demented subjects with non-Alzheimer dementias on pathological examination were Alz-50 negative. Alz-50 may stain plaques found in AD, but not stain plaques which accompany aging. The cognitive impairment found in the Alz-50 negative subjects may be age-associated and not indicate early AD. PMID- 2602415 TI - Tobacco use in Alzheimer's disease. AB - Cholinergic abnormalities in Alzheimer's disease (AD) may be important in the pathogenesis of memory impairment. Tobacco use, which might reflect changes in central nicotinic receptors, was examined by chart review of 272 patients (M:F 86:186) with "probable" AD by NIH criteria, and by interviewing next-of-kin of 39 patients (M:F 15:24) and spouse controls. On chart review, 37% of females and 98% of males had used tobacco, but only 10% of females and 14% of males were still smoking at AD onset. Interval between stopping smoking and AD onset was 18.3 +/- 7.7 years in females and 16.6 +/- 6.8 years in males. Losing the taste for smoking preceded cessation in 60.3% of females and 16.2% of males. Only 7.9% of females and 4.4% of males had withdrawal symptoms. Next-of-kin interview revealed that patients and controls were comparable in demographic data, alcohol use, and smoking habits. 24% of patients and 37% of controls had stopped smoking, often due to losing the taste for smoking (32% of patients; 18% of controls). Withdrawal symptoms occurred in 21% of patients and 41% of controls. Relative to controls, patients less frequently had increased appetite (28% vs 47%), but more often had changed sex drive (22% vs 0%) and altered preference for specific alcoholic beverages (11% vs 0%), after stopping smoking. In AD, the loss of desire to smoke, lack of nicotine withdrawal, and altered appetites long precede cognitive symptoms, suggesting preclinical changes in central nicotinic receptors, as well as possible diagnostic and therapeutic strategies. PMID- 2602416 TI - Linkage studies in familial Alzheimer's disease. PMID- 2602417 TI - Dementias in Swedish twins. PMID- 2602418 TI - Sib-pair linkage analysis in late onset Alzheimer's disease. PMID- 2602419 TI - Characteristics of familial Alzheimer's disease in nine kindreds of Volga German ancestry. AB - We report the clinical and neuropathological manifestations of Alzheimer's disease (AD) in nine kindreds of German ancestry all originating from the same two adjacent villages on the West bank of the Volga River. There have been 89 known demented persons (53 male, 36 female). Mean age of onset is 57.6 +/- 8.4 years with a range of 40 to 84. Mean age at death is 66.5 +/- 7.6 years with a range of 50 to 80. Mean disease duration is 10.3 +/- 4.8 years with a range of 3 to 23. Detailed medical records were available on 50 individuals. Of these, 24% had a seizure, 72% language disturbance, 36% rigidity, 16% tremor and 12% myoclonus. There were 15 autopsies on demented persons from 6 of the kindreds. One brain suggested Creutzfeldt-Jakob disease (CJD) in a woman with the typical clinical course. The remaining 14 brains showed typical neuropathological characteristics of AD including neuritic amyloid plaques, neurofibrillary tangles, amyloid angiopathy and granulovacuolar change. Amyloid plaques were also seen in the cerebellum in all but one brain in which this region was available for review. Autopsy material from five brains in four families has been stained with antibody directed against the amyloid peptide; in all cases, the neuritic plaques stained positively. Many of the families share common surnames. It is likely that these Volga German kindreds carry the same genetic mutation leading to Alzheimer's disease; and thus, they are a valuable resource for genetic investigations of AD. Thus far, the disease in these kindreds does not show close linkage to either the D21S1 or beta amyloid gene loci on chromosome 21. PMID- 2602420 TI - Mutation in the cystatin C gene causes hereditary brain hemorrhage. AB - Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disorder leading to massive brain hemorrhage and death in young adults (Jensson et al., 1987). A variant of a potent inhibitor of cysteine proteinases, cystatin C (Barrett et al., 1984), is deposited as amyloid fibrils in the cerebral arteries of the patients (Ghiso et al., 1986). We have used the full length cystatin C cDNA probe (Abrahamson et al., 1987) to demonstrate a mutation in the codon for leucine at position 68, which abolishes an Alu I restriction site in cystatin C gene of the HCCAA patients. The Alu I marker has been used to show that this mutation is transmitted only in the affected members in all eight families investigated, proving that the mutated cystatin C gene causes HCCAA. This DNA marker will be useful for the diagnosis of HCCAA in patients, asymptomatic affected individuals and also for pre-natal diagnosis. HCCAA is the first human disorder known to be caused by an abnormal gene for a cysteine proteinase inhibitor. PMID- 2602421 TI - Histopathological classification of dementias by multivariate data analysis. AB - Autopsied brains from 55 demented patients, clinically classified according to DSM-III criteria into AD/SDAT and MID and 19 nondemented individuals were available for this study. Using general clinical, gross neuroanatomical and histopathological data three separate dementia classes, namely AD/SDAT, MID and AD-MID, were visualized in two-dimensional space by multivariate data analysis. This analysis revealed that the pathology in AD-MID patients were not merely a linear combination of the pathology in AD/SDAT and MID, indicating that AD-MID might represent a dementia type of its own. PMID- 2602422 TI - Neuronal loss in the substantia nigra in patients with Alzheimer's disease and Parkinson's disease in relation to extrapyramidal symptoms and dementia. AB - Regional neuronal loss in the substantia nigra (SN) was studied in relation to extrapyramidal symptoms and dementia in 27 patients with Alzheimer's disease (AD), 12 patients with idiopathic Parkinson's disease (PD) and 18 controls. Four areas of the right SN were investigated at the level of the caudal red nucleus. In AD the number of neurons were reduced to 97%, 79%, 83% and 78% of the control values from the medial to lateral SN respectively. The number of lateral neurons showed a negative correlation with the severity of rigidity and hypokinesia. The degree of dementia did not have a significant correlation with nigral neuronal counts. In PD, the number of neurons was markedly reduced in all parts of the SN, most pronouncedly in the lateral part. The number of lateral neurons showed a negative correlation with the severity of rigidity and hypokinesia, whereas tremor had a positive correlation. The degree of dementia of the patients had a negative correlation with the number of medial neurons, suggesting that degeneration of the nigrostriatal neurons may contribute as a subcortical component to dementia in PD patients. PMID- 2602423 TI - Neuropathology of aminergic nuclei in Alzheimer's disease. AB - In order to comprehensively evaluate pathological involvement of the locus coeruleus (LC) and cortically projecting raphe nuclei in Alzheimer's disease (AD), we have recently completed a study (Zweig, et al., 1988) in which numbers of neurons containing neuromelanin within the LC and large nucleolus-containing neurons within the dorsal raphe nucleus (DR) and the central superior (raphe) nucleus (CSN) were determined in 25 cases of AD and 12 age-matched controls. Numbers of neurofibrillary tangles (NFTs) within these regions were also counted. Pathological results were compared with clinical data, including psychiatric evaluations, available for 21 of the AD cases. Neuronal loss in AD cases was most severe within LC at mid level (p less than .01) and within DR, caudally (p less than .05). Counts of NFTs within LC were also highest at mid level (p less than .05) in comparison with caudal level). Neuronal loss was not demonstrated within CSN, although NFTs were abundant within this nucleus. At individual levels, neuronal and NFT counts did not correlate. Relative severity of neuronal loss or NFTs was usually consistent from level to level within nuclei; internuclear correlations were weaker. Cases of AD complicated by depression had significantly fewer neurons at mid LC and rostral CSN levels than nondepressed cases (p less than .05). There was also a trend (nonsignificant) suggesting increased neuronal loss at all levels of LC and DR in depressed cases. Neuronal loss correlated negatively with age, particularly within LC. NFT counts correlated negatively with duration of illness, particularly within DR. As all but 3 individuals had severe dementia, NFT counts may reflect rate of progression of disease. Neuronal loss and NFTs frequently occur in the LC and cortically projecting raphe nuclei in AD (Curcio and Kemper, 1984, Hirano and Zimmermann, 1962, Ishii, 1966, Marcynuik et al., 1986, Yamamoto and Hirano, 1985, Bondareff and Mountjoy, 1986, Iverson et al., 1983, Mann et al., 1985, Tabaton et al., 1986). We have recently completed a comprehensive evaluation of pathological involvement of the LC, the DR, and the CSN in a series of aged controls and AD patients for whom detailed clinical information, including psychiatric evaluations, were available (Zweig et al., 1988). This report summarizes the findings of that study. PMID- 2602424 TI - Cytometrical and immunocytochemical investigation of brain nuclei in dementia. AB - Morphometrical investigation of brain nuclei in dementia of the Alzheimertyme and in other types of dementia has been done for the last 10 years. The N. Basalis of Meynert (Acetylcholine pathway) has been screened rather extensively by several groups. The L. Coeruleus (Nor-adrenergic pathway) also has been fairly well documented. The N. Raphe Dorsalis however-an important relay nucleus in the serotonergic pathway-was only studied cytometrically by a few groups. Other nuclei were not investigated systematically f.e. N. Accumbens; this nucleus might play an important role however in memory disturbances via Gabaergic influence on excitatory amino acids. This quantitative study focuses on those less well studied brain areas. A cytometrical analysis (cell counts-cell sizing) was performed on serial sections in clinically well-documented cases of different types of dementia: Alzheimer, Pick, Huntington, Jakob-Creutzfeldt. Results were compared with controls and for the N. Accumbens also with the values obtained in the brain of catatonic schizophrenics. The cell sizing and counting was done on cresylviolet sections, on modified Bielschowsky-stained sections and on Peroxidase-Anti-Peroxidase (P.A.P.) treated sections with a polycloncal antibody against Alzheimer Paired Helical Filaments (PHF). Our results show that the nerve cell degeneration in those nuclei is quite different in the diverse types of dementia, pointing to a disease specific physiopathology. PMID- 2602425 TI - Calcium antagonists protect hippocampal neurons against ischemic damage. PMID- 2602426 TI - Abnormalities of the glucose transporter at the blood-brain barrier and in brain in Alzheimer's disease. AB - We have previously demonstrated the glucose transporter (GT) by [3H]cytochalasin B binding and immunocytochemistry in brain and in cerebral microvessels which form the blood-brain barrier. In this study, we assessed the GT protein in the frontal cortex, hippocampus, cerebellum, and cerebral microvessels in subjects with Alzheimer's disease (AD) and controls. In AD, we found a marked decrease in the GT in brain microvessels and in the frontal cortex and hippocampus, regions that are classically affected in AD, but there were no significant changes in the cerebellum. The binding of [3H]cytochalasin B to frontal cortex was not correlated with age or with the interval between death and autopsy. The impairment of GT in cerebral microvessels and cortex in AD subjects is relatively specific and appears to be disease-related. Our findings may be associated with the decreased in vivo measurements of cerebral oxidative metabolism in AD. PMID- 2602427 TI - Characterization and possible role of growth factor and lymphokine receptors in the regulation of cholinergic function in the mammalian brain. AB - Using in vitro receptor autoradiographic techniques, we characterized the distribution of various growth factor (GF) and lymphokine receptors in the rat brain. In neonatal brain, specific insulin-like GF-1 (IGF-1) and epidermal GF (EGF) sites were observed in various regions. In particular, dense [125I]IGF-1 and [125I]EGF labelling was seen in the hippocampal formation. In the adult (3 month old) rat brain, a broader distribution of IGF-1 sites was apparent, whereas few EGF sites were visualized. As in the neonate, the adult hippocampus was enriched with IGF-1 binding sites. In addition, high levels of interleukin-2 (IL 2) binding sites were detected in the hippocampus of the adult rat. Exogenous IGF 1, EGF, and IL-2 significantly reduced the potassium (25 mM)-evoked release of acetylcholine (ACh) from slices of rat hippocampus. The GF effects were restricted to the adult hippocampus; neither IGF-1 nor EGF altered ACh release from slices of immature (6- and 18-day old) rat brain. Moreover, the GF and IL-2 mediated effects on ACh release appear to be specific to the hippocampus. For example, ACh release from frontal cortex or striatum was not significantly affected by either GFs or IL-2. In summary, our results suggest that in the rat hippocampus, IGF-1, EGF, and IL-2 may be important modulators of cholinergic activity. PMID- 2602429 TI - Morphometric analysis of Alzheimer's disease with Lewy bodies. PMID- 2602428 TI - Decrease in membrane-bound G4 form of acetylcholinesterase in postmortem Alzheimer brain. AB - Samples of left hippocampus, septal nucleus, parietal lobe (area 40), and nucleus basalis of Meynert (NBM) were removed from eight patients with pathologically confirmed Alzheimer's disease (AD), four controls, and three patients with non Alzheimer's dementia. Extracts of these brain regions were assayed for choline acetyltransferase (ChAT) specific activity, acetylcholinesterase (AChE) specific activity, and AChE molecular form composition. Average specific activities of ChAT from hippocampus, septum, and area 40, but not NBM, were significantly lower (p less than 0.01) in the AD population than in the control group. The average AChE specific activity was significantly less (p less than 0.05) in hippocampus and area 40 when the AD group was compared with controls. The average percentage of total AChE activity represented by the globular tetrameric (G4) molecular form was decreased in all AD brain regions as compared to control or to non Alzheimer's demented groups. The decrease in G4 was, in all cases, due to a selective decrease in the membrane-bound form of G4. The loss of percent membrane bound G4 in the AD group was significant for hippocampus (p less than 0.05) and area 40 (p less than 0.001) when compared to controls. The percentages of total AChE present as G4 and as membrane-bound G4 in each brain region were correlated with the ChAT specific activities in that region. The correlations showed that AChE molecular form composition changed significantly only if ChAT activity fell below a certain consistent level. The human data agreed well with data from fornix-lesioned mice which strongly suggest the existence of a soluble factor that regulates production of membrane-bound G4. PMID- 2602430 TI - Altered expression of neuronal messenger RNA in Alzheimer cortex. PMID- 2602431 TI - Neuritic plaques in the human fascia dentata: a model system for the study of plaque formation in Alzheimer's disease. PMID- 2602432 TI - Serum antibodies to cholinergic neurons in Alzheimer's disease. AB - Alzheimer's disease (AD) is associated with degenerative changes in nuclei of the basal forebrain which provide most of the cholinergic innervation of the cortex and hippocampus. Although the etiology and pathogenesis of AD are not known, several reports indicate the involvement of immunological mechanisms. In the present work we examined the existence of antibodies in sera of AD patients which bind specifically to cholinergic neurons. As antigen we employed the purely cholinergic electromotor neurons of the electric fish Torpedo which are chemically homogeneous and cross react antigenically with human and other mammalian cholinergic neurons. Our findings show that immunoglobulins (IgG) from sera of AD patients bind to the heavy neurofilament subunit (NF-H) of these neurons. Comparison of the binding of AD and control IgG to Torpedo cholinergic NF-H revealed that AD IgG bind to this neurofilament protein more than control IgG. In contrast, AD and control IgG bind similarly to NF-H obtained from the chemically heterogeneous Torpedo spinal cord and from rat brain. These findings suggest that AD sera contain a repertoire of anti NF-H IgG and that a subpopulation of these antibodies, whose levels are significantly elevated in AD, binds to epitopes highly enriched in Torpedo cholinergic NF-H. The diagnostic potential of these AD antibodies is discussed. PMID- 2602433 TI - The preliminary characterisation of a protein present in cerebrospinal fluid and serum using a monoclonal antibody which reacts immunohistochemically with amyloid deposits in Alzheimer brains. PMID- 2602434 TI - DNA repair deficiency for alkylation damage in cells from Alzheimer's disease patients. AB - We have shown that fibroblasts, lymphocytes and lymphoblasts from patients with Alzheimer's disease (AD) are deficient in the repair of DNA damage induced by the alkylating agents methylmethane sulfonate (MMS) and N-methyl-N'-nitro-N nitrosoguanidine (MNNG). Unscheduled DNA synthesis and alkaline elution studies of DNA repair using human skin fibroblasts obtained from patients coming to autopsy have shown that the cells from autopsy confirmed cases of AD have lower levels of DNA repair synthesis after exposure to varying concentrations of either MMS or MNNG. Lymphoblasts derived from individuals with dominantly inherited AD have also been used to study DNA repair. Alkaline elution analysis of DNA repair after exposure to 200 uM MMS or 6 uM MNNG indicates that there is significantly less repair in the lymphoblasts from AD patients. When healthy control cell lines repaired and cell lines from AD patients were exposed to MMS or MNNG respectively significantly less repair occurred in the AD cells. After studying five at risk individuals results indicate that cell lines from two of these people have low levels of DNA repair and three lines have normal repair. These findings support the hypothesis of a DNA repair deficiency in familial AD. Monocytes from healthy control subjects and putative AD patients were analyzed for mutant frequency and DNA repair capacity. Results of unscheduled DNA synthesis experiments using monocytes from 7 healthy controls and 9 presumed AD patients indicates that there is a decreased ability of AD cells to repair MMS and MNNG induced DNA damage. PMID- 2602435 TI - Characterisation of the first monoclonal antibody against the pronase resistant core of the Alzheimer PHF. AB - A monoclonal antibody, NOAL 6.423 has been produced which unequivocally identifies a protein which is a constituent of the pronase resistant core of the Alzheimer PHF. Although the site recognised by this antibody is contained somewhere within the highly conserved triple repeat region of the tau molecule, no experiments have succeeded so far in demonstrating NOAL 6.423 reactivity in any brain proteins other than those derived from PHFs. A site which can be recognised by NOAL 6.423 cannot be generated in preparations of normal porcine tau by simple proteolytic cleavage with pronase. Likewise reactivity with the PHF peptide recognised by NOAL 6.423 is not altered by alkaline phosphatase. The unusual properties of NOAL 6.423 are consistent with the possibility that its recognition site is not determined solely by the primary structure of the conserved region of the tau molecule. PMID- 2602436 TI - Do nematosomes play a role in the formation of paired helical filaments (PHF) in dorsal root ganglia (DRG) of rats? AB - The lack of a suitable animal model for Alzheimer research continues to be an impediment to the elucidation of the pathogenesis of the histological features of this condition, including PHF. Chronic ethanol intoxication induces the formation of PHF in young rats. Abnormalities in number and subcellular distribution of nematosomes in DRG of rats subject to chronic ethanol feeding has been noted by us. We present evidence that a vitamin A deficient diet promotes the formation of PHF and nematosomes in DRG of rats chronically intoxicated with ethanol. Three groups of young male Wistar BR rats were implanted with a gastrostomy cannula and infused with the following liquid diet: first group received 30% of total calories as corn oil, 32% ethanol, 25% protein with the balance as dextrose; 5% lard was substituted for the corn oil in the second group; the third group received 25% corn oil and was maintained in a vitamin A deficient state. Control animals were pair-fed the diet and isocaloric in dextrose with the experimental animals' alcohol intake. Animals were sacrificed at approximately 150 days and DRG were fixed in situ with a solution containing 2% paraformaldehyde and 2% glutaraldehyde. The increased number of nematosomes in all ethanol treated rats was prominent and more so in animals with a vitamin A deficient diet. A large amount of lipofuscin was usually associated with these thread-like structures which were of several types. Nematosomes commonly enclosed neurofibrillary tangles of PHF in animals treated with the ethanol-vitamin A deficient diet. PHF were rarely observed in other animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602437 TI - Geriatric assessment programs benefit dementia patients and their families. PMID- 2602438 TI - Menopause: evaluation, treatment and health concerns. Proceedings of a National Institutes of Health symposium. Bethesda, Maryland, April 21-22, 1988. PMID- 2602439 TI - The impact of menopause and social factors on health. PMID- 2602440 TI - Psychological experience of the climacteric and postmenopause. PMID- 2602441 TI - Menopause and the epidemiology of cardiovascular disease in women. PMID- 2602442 TI - Brain entry and direct central pharmacological effects of the nootropic drug oxiracetam. Oxiracetam: brain entry and pharmacological effects. AB - Oxiracetam administered systemically to rats as a 14C radiolabelled drug (200 mg/kg p.o. or 100 mg/kg intra-artery) enters the brain and is found unmetabolized above all in some of the brain areas functionally involved in the modulation of cognitive processes. Among the brain areas examined, the largest amount of compound was recovered in septum, followed by hippocampus; a smaller amount was found in cerebral cortex and striatum. 14C oxiracetam administered directly into the lateral ventricles of the brain presented a similar pattern of distribution, indicating that the tropism of the drug for the above brain areas does not depend on its route of administration. The amounts of oxiracetam that could reach the brain after systemically administered pharmacologically active doses were also estimated. These amounts (1.9 to 19 nmols/rat) were delivered through a permanently implanted cannula, into the lateral ventricles of the brains of conscious, freely moving rats. In this experimental condition oxiracetam dose dependently antagonized the amnesia induced by scopolamine (0.66 mg/kg s.c.). The above findings clearly indicate that oxiracetam enters the brain and directly exerts its pharmacological activity there. PMID- 2602443 TI - The relationship between the behavioral effects of cognition-enhancing drugs and brain acetylcholine. Nootropic drugs and brain acetylcholine. AB - The effect of different doses of the cognition-enhancing agent oxiracetam on the disruption of acquisition of a passive avoidance conditioned response (step through) by scopolamine 0.6 mg/kg s.c., and on the impairment of performance by scopolamine 0.2 mg/kg s.c. in an eight-arm maze was investigated in adult male Wistar rats. At the end of the experiments, ACh levels were measured in the cerebral cortex and hippocampus by an HPLC method, in order to ascertain whether a relationship exists between the effects of the two drugs on behavior and cholinergic function. In the step-through test, oxiracetam at doses of 50 and 100 mg/kg s. c., given 30 min. before scopolamine, antagonized both scopolamine induced behavioral disruption and decrease in ACh levels but was inactive at the dose of 300 mg/kg s. c. In the eight-arm maze test, oxiracetam prevented scopolamine-induced disruption of the performance and decrease in brain ACh at the dose of 30 mg/kg s. c. but was inactive at the dose of 100 mg/kg s. c. In conclusion, when scopolamininduced disruption of behavior is prevented or reduced, the scopolamininduced decrease in ACh level, particularly in the hippocampus, is also reduced. The present results therefore offer further confirmation of a relationship between the cognition-enhancing effects of oxiracetam and its effects on hippocampal and cortical cholinergic mechanisms. PMID- 2602444 TI - Effects of phosphatidylserine administration of aged-related structural changes in the rat hippocampus and septal complex. AB - Dendritic spine density of CA1 pyramidal neurons in the hippocampus and morphometric characteristics of the cholinergic neuronal population of the septal complex, were evaluated in young (four months), aged (27 months), and age-matched rats which had received long-term phosphatidylserine (BC-PS) administration (50 mg/kg/die, suspended in the drinking water). In aged rats, spine density decreased significantly by 12.11% in the basal dendrites and by 10.64% in the apical ones, as compared with young controls. In the cholinergic neuronal population of medial septum and diagonal band, aging induced a statistically significant reduction in cell number (-19.6%), in soma area (-18.5%), in cell maximal diameter (-9.2%), and in the area covered by all cholinergic profiles ( 33%). By contrast, no significant reductions in the above-mentioned structural parameters were observed in aged BC-PS-treated rats when compared with young animals. The mechanisms underlying the beneficial effects of BC-PS can possibly be ascribed to the pharmacological actions exerted by BC-PS on neuronal membranes, neurotransmission, and/or interaction with NGF. PMID- 2602445 TI - New drugs in memory and learning. Proceedings of the CINP symposium. 1988. PMID- 2602446 TI - You can make the difference. PMID- 2602447 TI - Laboratory animal issues broadened with new focus on use by high schools. PMID- 2602448 TI - Metabolic changes caused by irregular-feeding schedule as compared with meal feeding. AB - In this study rats eating 50% of the quantity of daily food intake observed for free-fed rats were restricted to regular (MF) and irregular intermeal (IF) intervals. Rats which had free access to food (FF) were also included. The experiments were carried out for 1, 2, 3 and 4 weeks. Body weight, daily food intake, stomach fresh weight, blood glucose and free fatty acids (FFA) levels, liver glycogen content and adrenal ascorbic acid were evaluated. The results showed that adaptative metabolic pattern depends on the discipline of the intermeal intervals. Meal-fed rats with a fixed meal time showed better blood glucose maintenance, slower gastric emptying, increased liver glycogen content and lower FFA mobilization during 22-hr fast than the free-fed group. The same amount of food eating by meal-fed rats given randomly in time (IF) promoted a different adaptative metabolic pattern. The results suggest that the regular intermeal period is an important factor for the establishment of the metabolic changes. Therefore, the meal-feeding schedule has to be considered as a particular modality of food restriction. PMID- 2602449 TI - Fetal, hormonal and experiential factors influencing the mating-induced regulation of infanticide in male house mice. AB - When a male house mouse encounters a neonate he either attempts to kill it or he does not harm it. An unusual aspect of his response is that adaptive, time dependent changes in behavior toward pups result from a unique stimulus-response system triggered specifically by ejaculation. In virgin male CF-1 mice, about 50% of all males are spontaneously infanticidal when they encounter a pup while the other 50% are typically "parental." The stimulus of ejaculation causes virtually all males to kill pups; however, by the time offspring are born three weeks after mating, infanticide is inhibited and almost all males now behave parentally toward pups. Our experiments examine fetal, experiential, and hormonal factors influencing the changes in infanticidal and parental behavior that occur in male mice as a result of mating. Males who developed in utero between two female fetuses, and were thus exposed to relatively low testosterone concentrations during fetal development, were significantly more likely to exhibit infanticide- both before and after mating--than were males who developed between two male fetuses. Concurrent exposure to testosterone appears required in order for naive males to exhibit infanticide and for spontaneously parental males to become infanticidal after ejaculation. In contrast, neither testosterone nor pituitary hormones appeared responsible for the timed inhibition of infanticide occurring by three weeks after mating, since castrated and hypophysectomized males showed a response pattern similar to intact males. The mating-induced inhibition phenomenon appears to be a neurally timed and mediated response that operates independently from pituitary hormone secretions or changes in gonadal hormones resulting from mating. PMID- 2602450 TI - Sensitization of sympathetic-adrenal medullary responses to a novel stressor in chronically stressed laboratory rats. AB - Studies from this and other laboratories have demonstrated that sympathetic adrenal medullary responses are reduced in laboratory rats exposed to chronic intermittent stress. To extend these findings, we have conducted three experiments in which laboratory rats were exposed daily for 26 consecutive days to the same (homotypic) stressor and then challenged with a novel (heterotypic) stressor. Each stress session lasted for 30 minutes and the following homotypic/heterotypic treatments were included: Experiment 1- restraint/footshock; Experiment 2--cold swim/restraint; and Experiment 3- footshock/cold swim. Controls were exposed to the heterotypic stressor only. Plasma levels of norepinephrine (NE) and epinephrine (EPI) were measured in blood samples taken from control and chronically stressed rats to provide an assessment of sympathetic-adrenal medullary activity. In each experiment, chronically stressed rats gained significantly less weight than handled controls. Basal plasma levels of NE and EPI were similar for chronically stressed and control rats. In contrast, plasma catecholamine responses to the heterotypic stressor were significantly greater in stressed rats compared to controls that were stressed for the first time. This pattern of exaggerated responses was especially evident for the cold swim/restraint and footshock/cold swim groups. These findings provide evidence for a sensitization of sympathetic-adrenal medullary responses to a novel stressor in animals previously exposed to chronic intermittent stress. PMID- 2602451 TI - Effect of chronic administration of dexfenfluramine on stress- and palatability induced food intake in rats. AB - Dexfenfluramine, administered chronically either SC via osmotic minipump (3 mg/kg/day) or as daily IP injections (1.5 mg/kg) to rats, suppressed tail pinch induced eating for up to 14 days. The minipump regimen also caused a reduction of intake of a palatable "dessert" for up to 9 days in heavy, adult rats, but was only transiently effective in young, rapidly growing rats. Nonetheless, the regimen produced decreased weight gain and insensitivity to a subsequent acute test dose of the agent. These results illustrate the sustained anorectic efficacy of dexfenfluramine in paradigms that do not involve restriction of diet, and these may be animal models of snacking or binging. The data also corroborate previous suggestions that the agent is more effective in older or more obese populations. PMID- 2602452 TI - Clip-induced analgesia: noxious neck pinch suppresses spinal and mesencephalic neural responses to noxious peripheral stimulation. AB - Pinch of the nape of the neck, of mice, with a serrated clip, produces immobility and lack of responsiveness to noxious stimulation. In this study we attempted to determine whether clip application produces true blockade of nociception, independent of its immobilizing effect, and examined the level of the neuroaxis at which such an effect takes place. To this end nociception was measured using indices not requiring a motor response. Neck pinch eliminated the elevation of heart rate induced by noxious pinch of the tail without affecting heart rate by itself providing evidence for its analgesic effect. Direct evidence that neck pinch suppresses the transmission of noxious information is also provided. Neck pinch inhibits neural activity evoked by noxious peripheral stimulation while exerting minimal effects on the effects of nonnoxious stimuli. Thus, sensory evoked activity in the periaqueductal gray area, elicited by noxious electrical stimulation, but not innocuous stimuli, is inhibited by neck pinch. Similarly, neck pinch inhibits the response of spinal cord neurons to noxious but not nonnoxious stimulation. It, therefore, appears that neck pinch produces true analgesia by activating supraspinal systems which in turn acts to inhibit the transmission of nociception both at spinal and supraspinal levels. PMID- 2602453 TI - Critical exposure time for androgen activation of male sexual behavior in rats. AB - We determined the minimum number of hours per day of testosterone (T) exposure required to activate male sexual behavior, and correlated these changes with the temporal parameters of androgen receptor occupation. For the first part of the study, castrated Long-Evans male rats received two 10 mm T-filled Silastic capsules in open flank pouches for 4, 8, 12, 16, 18, 21, or 24 hours per day over a 10 day period. Tests for male sexual behavior were conducted on days 2-3, 4-5, 7-8, and 9-10 of T treatment. A significantly higher proportion of males receiving 21 or 24 hr of daily T exposure mounted, intromitted and ejaculated compared to groups with daily T exposures of 18 hr or less. In the second part of this study we assessed whether it was necessary to maintain high levels of androgen receptor occupation during the 21-24 hr exposure period in order to activate male sexual behavior. Cell nuclear androgen receptor occupation was measured in HPAS (combined hypothalamus, preoptic area, amygdala and septum) of rats receiving 12, 21, or 24 hr of T exposure. In all three groups, nuclear androgen receptor occupation was high at the time of capsule removal, and fell significantly by 3 hr following T capsule removal. By 6 hr after T capsule removal, androgen receptor binding had fallen to castrate levels. These results demonstrate that, although relatively brief (less than or equal to 18 hr/day) exposures to testosterone can activate mounts and intromissions, significantly more responses are found in males receiving at least 21 hr of T exposure per day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602454 TI - Repeated hypothalamic stimulation with neuropeptide Y increases daily carbohydrate and fat intake and body weight gain in female rats. AB - Neuropeptide Y (NPY), repeatedly injected in the hypothalamic paraventricular nucleus (PVN), produces dramatic obesity and overeating in female rats maintained on a single nutritionally complete diet. In the present study, we investigated whether these effects could also be obtained in animals with a choice of three pure macronutrients: protein, carbohydrate, and fat. Female rats with indwelling PVN cannulas were injected with NPY (235 pmol) or its saline vehicle every 8 hr for 6 days. A third group was left undisturbed. Consumption of each macronutrient and body weight were measured every 24 hr for 6 days preinjection, 6 days during injections, and 21 days after the injections were terminated. Relative to vehicle or preinjection rates of body weight gain (approximately 1.5 g/day), NPY dramatically enhanced weight gain to a rate of 9.3 g/day and more than doubled total daily food intake. This augmentation was accounted for by increases in carbohydrate intake (+26.4 kcal/day) and fat intake (+48.5 kcal/day), with no significant potentiation of protein consumption. When the NPY injections were terminated, body weight and macronutrient intake returned to control levels within 1 or 2 weeks. These findings are consistent with a role for NPY in hypothalamic mechanisms of macronutrient intake and body weight regulation and suggest that disturbances in brain NPY may contribute to the development of eating and weight disorders. PMID- 2602455 TI - Sleep changes in fasting rats. AB - The proportion and the distribution of wakefulness (W) slow-wave sleep (SWS) and paradoxical sleep (PS) were studied in 27-week-old rats over 24 hr periods, both in the fed state and after having been deprived of food for 2 to 3 weeks. In these rodents, prolonged fasting has been characterized by 3 successive metabolic phases which have been found to correspond to changes in protein metabolism. Sleep-waking changes were not studied during the first phase which was often of short duration (24 hr). During the second phase, i.e., when proteins were spared, the 24 hr proportions of W and sleep states remained unchanged. There were, however, profound changes in the daily mean episodic characteristics of each vigilance state (duration and frequency) except in the case of PS. During the phase II, the differences in the day/night proportions observed in each vigilance state were less than in the fed state. This reflected a lowering in the amplitude of their daily rhythms. In contrast, when protein use rose (phase III), W was increased sharply at the expense of SWS and PS, the latter being almost completely suppressed. During this last phase, which was also of short duration (by mean 3 days) alertness was greatly enhanced and the rats, which were typically nocturnal when fed, became diurnal. The changes in sleep and wakefulness were examined in relation to their effects on the homeostatic and cyclic components of sleep mechanisms and adaptive strategy to food deprivation in rat. PMID- 2602456 TI - Testosterone supports hormone-dependent aggression in female rats. AB - Female hooded rats were ovariectomized and implanted with a single testosterone filled Silastic tube or an empty tube. The tube size was one which allowed a release of testosterone at the high end of the mean normal serum testosterone concentration for intact females. Following a 7-day recovery period, all rats were placed on a 23-hr food-deprivation schedule and adapted to a highly palatable liquid food over a 5-day period. Each animal with a testosterone implant was then housed with an animal of similar weight but an empty implant. The pairs were subjected to a series of 3 restricted-access competition tests (1/day) followed 4 days later by a series of 3 free-access competition tests. The animals were then separated, adapted to a bland liquid food, and paired with new partners. They were then subjected to the restricted- and free-access food competition tests but with bland food as the incentive. During the first 6 competition tests there were no significant differences between groups in aggression or in time spent licking at the food spout. During the second series of tests, females with testosterone implants were more aggressive and more successful at maintaining access to the food than were their competitors with empty implants. The difference between groups occurred during the free- as well as the restricted-access tests. The effectiveness of physiological levels of testosterone in supporting aggression is attributed to the use of a test situation that activates as well as elicits hormone-dependent aggression. These results suggest that testosterone may be the hormonal substrate for hormone dependent aggression in female rats. PMID- 2602457 TI - Posttraining or pretest administration of nimodipine fails to affect retention of a simple learned association. AB - In previous experiments, the antagonist of voltage-sensitive calcium channels, nimodipine, given before training, enhanced the retention of an acquired preference for white-left relative to black-right in a two compartment apparatus. In the present experiments we attempted to determine if the retention effects produced by the drug could be attributed to effects occurring in the posttraining period. Various groups of rats received posttraining injections of nimodipine or its vehicle and two hours prior to testing received a second injection of nimodipine or its vehicle or no injection at all. All rats were tested for retention of the association twice, both 24 and 48 hr after acquisition. No posttraining or pretesting drug effects were found. This would support the view that the enhanced retention found after treatment with nimodipine found by ourselves and by others is due to a change in the animals at the time of acquisition. PMID- 2602458 TI - Effect of interscapular brown adipose tissue denervation on body weight and feed efficiency in alcohol drinking rats. AB - In rats, chronic alcohol intake increases energy expenditure and enhances interscapular brown adipose tissue (IBAT) mass and activity. It is known that alcohol intake is mainly preprandial. In man, alcohol intake during a meal increases postprandial thermogenesis. Since diet-induced thermogenesis is mediated by the sympathetic nervous system, the effect of IBAT surgical denervation was examined on body weight (BW), food intake (FI) and feed efficiency (FE) in alcohol drinking rats. Alcohol drinking rats gained significantly less BW than water drinking rats; FI was identical and so FE was less in alcohol-treated animals. After sympathectomy, the water drinking group was identical to its own control group for BW gain, FI and FE. BW gain of sympathectomized drinking rats was significantly higher than that of controls. FI and FE were nearly identical. It is concluded that the increase in thermogenesis observed in chronic alcohol-treated rats is partly suppressed by sympathectomy. This increase could also involve other BAT mass and other tissues in the whole rat. PMID- 2602459 TI - Neuroleptic-induced emotional defecation: effects of pimozide and apomorphine. AB - Neuroleptics, such as haloperidol, have been found to produce dysphoria, anxiety and akathisia in humans. In animals, these effects have rarely been reported since the decreased movement produced by these drugs can confound the study of many behavioral indices of emotionality. In fact, most investigators have found a decrease in emotional defecation in rats given neuroleptics in novel environments, supporting their action as a major tranquilizer. We have found, however, that in rats a profound increase in emotional defecation can result from haloperidol administration in well habituated environments, such as the homecage. In male rats, defecation was measured for a one hour test period following various doses of the neuroleptic, pimozide, and the dopamine receptor agonist, apomorphine. Apomorphine and pimozide (a dopamine receptor antagonist) were both found to increase levels of fecal boli excretions. In addition, when apomorphine was combined with haloperidol, defecation levels were also increased suggesting that this phenomenon is not directly mediated by dopamine receptors. It is suggested that this drug-induced defecation is a consequence of the agent's interaction with the affective state of the animal, creating a dysphoric or anxious state in the animal. PMID- 2602460 TI - Central versus peripheral effects on temperature preference and body temperature following alteration of 5-HT in maturing mice. AB - Experiments were designed to distinguish between central and peripheral effects on temperature preference and body temperature of drugs injected intraperitoneally (IP) in infant mice ranging in age from 3 to 10 days postpartum. These compared a drug restricted to the periphery ("peripheral" drug) with a drug of similar action that reaches the central nervous system (CNS) as well as the periphery. Two different classes of drugs were utilized to test central versus peripheral actions independently with drugs that have different modes of action: 1-aromatic amino acid inhibitors and serotonin receptor antagonists. Although the decarboxylase inhibitor NSD 1015, which reaches the central nervous system from IP injection, can significantly decrease temperature preference (Tpref), the peripheral inhibitor carbidopa had no significant effects on Tpref or on body temperature (Tb). Furthermore, pretreatment with NSD 1015 prevented the elevation of Tpref produced by the serotonin precursor 5 hydroxytryptophan (5-HTP); however carbidopa pretreatment had no effect on the increased Tpref produced by 5-HTP. In other experiments, the peripheral serotonin antagonist BW 501C was not able to prevent elevated Tpref produced by 5-HTP, although the specific 5-HT2 antagonist pirenperone, which reaches the CNS as well as the periphery, blocks the 5-HTP elevation of Tpref. Taking all of these results together, we conclude that the changes in Tb and Tpref following these treatments require a decarboxylase inhibitor or 5-HT antagonist that reaches the CNS. However, the well known and potent peripheral vasoconstrictor action of serotonin requires that peripheral effects of drugs be considered when manipulations are not restricted to the CNS. PMID- 2602461 TI - The effect of dexamethasone-21-acetate on meal size, meal frequency and macronutrient self-selection in rats. AB - In Experiment 1, the measurement of 24-hour food intake in two rats showed that treatment with dexamethasone-21-acetate (DEX) (0.5 mg/kg IP) produced a decrease in body weight which was at least partially due to a decrease in food intake (both meal frequency and meal size). In Experiment 2, the daily intake of three macronutrient sources was measured. These data showed that treatment with DEX (0.5 and 1.0 mg/kg IP) led to an acute increase in protein intake, a sustained decrease in fat intake and no change in carbohydrate consumption. We suggest that this change in macronutrient selection may be an adaptive response which serves to ameliorate some of the effects of DEX treatment. PMID- 2602462 TI - Dissociation of opioid and nonopioid analgesic responses following adult monosodium glutamate pretreatment. AB - Neonatal administration of monosodium glutamate (MSG: 2-4 mg/g, SC) selectively destroys circumventricular organs, especially the arcuate nucleus and median eminence of the hypothalamus, and also attenuates both nonopioid (continuous cold water swim: CCWS) and opioid (morphine) analgesia when rats are tested as adults. The present study evaluated whether administration of MSG (1-6 g/kg, SC) or its equiosmotic control (2.37 M NaCl) to adult rats altered either basal nociception on the tail-flick and jump tests or analgesia following morphine (5 mg/kg, SC) or CCWS (2 degrees C for 3.5 min). MSG treatment dose-dependently produced small but significant increases in basal nociceptive thresholds in adult rats. Morphine analgesia was significantly reduced on both tests following pretreatment with MSG (30-32%) and hypertonic NaCl (17-25%). In contrast, MSG (55-247%), but not NaCl pretreatment potentiated both nonopioid CCWS analgesia on both tests and CCWS hypothermia. These data are discussed in terms of differential neonatal and adult MSG effects, dissociations between opioid and nonopioid pain-inhibition, and the role of MSG in altering adaptive mechanisms to environmental stressors. PMID- 2602463 TI - Eating attitudes and taste responses in young ballerinas. AB - The Eating Attitude Test 40 (EAT 40) was administered to 23 ballerinas (mean age 18.3 +/- 0.9 years). The scores were high, as they are in anorexic patients. The EAT 40 revealed anorexic-like attitudes in dancers: selective food restrictions, severe dieting, constant preoccupations with food. However, dancers scored low at items screening bulimia, vomiting or laxative abuse. The dancers' perceptions and preferences for sweetness and fat food content were examined and compared to those of 14 sedentary controls. Taste stimuli were 20 semiliquid mixtures of soft white cheese (0, 3 or 7 grams of fat per 100 grams) or heavy cream (30% fat), and sweetened with 1, 5, 10, 20 or 40% sucrose. The subjects used a 9-point category scale to rate the perceived sweetness, fat content, and hedonic value of the stimuli. There were no significant differences in the perceived sweetness intensity between groups, but the perception of fat appeared to be better in dancers, in particular in very sweet stimuli. Dancers showed a clear aversion for the fattest stimuli. In young female dancers, enhanced sensitivity for alimentary fats is associated with decreased preferred levels. PMID- 2602465 TI - Controllability of prestimulation of the medial prefrontal cortex determines the facilitation of self-stimulation and kindled seizures. AB - Electrical stimulation of the medial prefrontal cortex (MPC) was administered according to the triadic design typically used to demonstrate learned helplessness. Three groups received either controllable, uncontrollable or no stimulation during the pretreatment phase. The effects of this pretreatment on the acquisition of self-stimulation at the same electrode site were investigated in the second phase of the experiment. Relative to unstimulated controls, both controllable and uncontrollable prestimulation facilitated the acquisition of self-stimulation and produced higher self-stimulation rates. In addition, compared with controllable stimulation, pretreatment with uncontrollable stimulation produced a greater facilitation in self-stimulation rate. The unambiguous demonstration of a behavioural facilitation produced by pretreatment with uncontrollable stimulation is, effectively, the inverse of the typical learned helplessness finding. It was also found, in the second phase of the experiment, that 6 of the 7 rats previously exposed to uncontrollable stimulation developed full class 5 seizures. No behavioural evidence of kindling was seen in any of the other rats or during the prestimulation procedure. These data are interpreted in terms of kindling and stress effects both proximal and distal to the site of stimulation. PMID- 2602464 TI - Learned immobility explains the behavior of rats in the forced swimming test. AB - The rat forced-swimming test (FST) is widely used for screening substances with a potential antidepressant effect. The rat immobility shown in the FST has been interpreted as "behavioral despair" and has been suggested as an animal model of human depression. In the following series of experiments it is shown that measuring rat mobility by an automatic recording device is more accurate than measuring immobility time by direct observation (Experiment 1 and 5). The automatic recording procedure was tested with imipramine and mianserin showing similar results to those reported in the literature using a direct observation procedure by the researcher (Experiment 2). In Experiment 3 it was demonstrated that: (a) rat mobility decreased with experience, (b) switching water depth on Day 2 of the test increased mobility and (c) anisomycin acts as a false positive. In Experiment 4 the possible state dependent effect of imipramine in the FST was studied. The effect of imipramine on rat behavior in the FST is not state dependent. The imipramine-saline group shows greater mobility than the saline saline group and does not differentiate from the imipramine-imipramine group. Thus, it was suggested that imipramine could interfere with the acquisition and/or consolidation processes. In Experiment 5, it is shown that a single dose of 25 mg/kg of imipramine, administered before or immediately after training on Day 1, increases rat's mobility on Day 2, thus suggesting that imipramine alters the consolidation process. From these results it is suggested that the behavioral process involved in the FST is "learning to be immobile" instead of "behavioral despair" as previously suggested in the literature. PMID- 2602466 TI - Inverse relationship between intensity of vaginal self-stimulation-produced analgesia and level of chronic intake of a dietary source of capsaicin. AB - Women who chronically ingest a diet rich in capsaicin, the pungent ingredient in hot chili peppers, showed a significantly lower magnitude of analgesia in response to vaginal self-stimulation than women with relatively low or medium levels of ingestion. Vaginal self-stimulation-produced analgesia was quantified by measuring (on the hand) pain detection thresholds, pain tolerance thresholds and tactile thresholds. Whereas vaginal self-stimulation produced a 32.6-43.8% increase in pain detection and pain tolerance thresholds in the low chili diet group, it produced only a 2.3-7.3% increase in these measures in the high chili diet group. The medium chili diet group showed an intermediate effect on the pain thresholds. Tactile thresholds were not increased by the vaginal self stimulation. Baseline (no stimulation) pain thresholds did not differ significantly among the three groups. These findings are consistent with earlier studies in laboratory rats, in which capsaicin administered neonatally abolished vaginal stimulation-produced analgesia, but did not affect baseline pain thresholds to mechanostimulation. PMID- 2602467 TI - Intertrial interval dependent effect of lateral hypothalamic stimulation on spontaneous alternation behavior in a T-maze. AB - Spontaneous alternation behavior in a T-maze was studied in mice of the BALB/c strain implanted with a stimulation electrode in the lateral hypothalamus (LH). For animals receiving no electrical stimulation spontaneous alternation rates decreased as a function of the increasing time interval between the first and the second trial (intertrial interval ITI). Thus, as compared to chance rate alternation (41.4%), mice significantly alternated at the 30 sec ITI (73.2%), exhibited a slight but not significant tendency to alternate at 30 min (51.8%) and performed very close to chance at 6 hr (39.3%). Stimulation of the LH, using a low current intensity (5 microA) during the first arm-choice, modifies subsequent arm-choice tested on the second trial. The direction of the effect, however, is highly dependent on the ITI. Thus, as compared to nonstimulated animals, stimulated mice show a strong preference to return to the previously visited arm when the ITI was 30 min, while for an ITI of 6 hr they, in fact, significantly avoid that arm (alternation). These results indicate that LH stimulation induces facilitative effects on memory for events occurring on the 1st trial as clearly shown for the 6 hr ITI. In addition to its general facilitative effect, stimulation could induce a place-reward association of short duration which could explain the fact that animals tend to return to the same arm at 30 min. Alternatively, it is suggested that stimulation might have short lasting amnesiant properties. Both of these hypotheses are discussed. PMID- 2602468 TI - The effect of wheel running and the estrous cycle on energy expenditure in female rats. AB - In female rats, food intake and wheel running fluctuate with the estrous cycle, creating a state of oscillating energy balance. The effect of the estrous cycle on the energy expenditure of conventionally housed rats (S) and of rats given access to an activity wheel (A) was compared. Over 24 weeks, the weight gain of the groups was similar although the body fat content of A was 30 g lower than that of S at the end of the study. During the assessment of energy expenditure by indirect calorimetry estrous cycles were disrupted and food intake and wheel running reduced. However, a correlation between expenditure and wheel running was obtained from which the cost of activity was derived (21 kJ/kg/km) and from which data were extrapolated to normal circumstances. This revealed that A, running on average 6214 rev/day, expended approximately 64 kJ/day more than S. This they compensated for by increasing their food intake by 6 g/day (70 kJ/day). Over the estrous cycle wheel running was maximal at proestrus and minimal at metestrus- the reverse trend in food intake was observed. This cyclic difference in energy balance between metestrus and proestrus was estimated to be equivalent to 23% of the 'maintenance' requirement. Thus voluntary activity bears a marked impact on day to day energy balance but has little effect in the long-term since in the female rat intake is precisely regulated to meet expenditure. PMID- 2602469 TI - Progesterone can either increase or decrease weight gain and adiposity in ovariectomized Syrian hamsters. AB - We examined the effects of estradiol and progesterone on weight gain, food intake, and carcass composition in Syrian hamsters (Mesocricetus auratus). In ovariectomized (OVX) hamsters injections of 5 micrograms/day estradiol benzoate (EB) alone decreased weight gain and adiposity, whereas treatment with progesterone alone (1 or 5 mg/day) resulted in increased weight gain and adiposity. However, concurrent treatment with progesterone and EB reduced body fat content to levels significantly below those of hamsters treated with EB alone. In a second experiment, 17 beta-estradiol and progesterone were administered via subcutaneous Silastic capsules in doses which produce physiological levels of steroids. Implants of estradiol significantly decreased body weight gain and fat content. As in the first experiment, these effects of estradiol were exaggerated by concurrent progesterone administration. Implants of progesterone alone did not affect body weight or fatness in OVX hamsters. These data indicate that estradiol and progesterone interact to decrease body lipid stores in hamsters, whereas in rats progesterone reverses the adiposity-reducing actions of estradiol. This species difference in responses to progesterone could help to explain why rats increase, whereas hamsters decrease, their body lipid stores during pregnancy, when circulating progesterone levels are elevated. PMID- 2602470 TI - Growth hormone secretion and ultradian rhythms in growth-retarded rats with dorsomedial hypothalamic lesions. AB - Rats with lesions of the dorsomedial nucleus of the hypothalamus (DMN-L) are hypophagic and have reduced linear growth and body weight, but normal body composition. Male Sprague-Dawley rats (170-190 g) housed individually under a 12:12 L:D schedule with lights out at 1430 hr received jugular cannulas, and on return to precannulation body weight (4.2 +/- 0.6 days), they received bilateral electrolytic DMN-L or sham-operations (SHAM). Rats with DMN-L (n = 8) were hypophagic postsurgery and weight less (p less than 0.05) than SHAM at six days postlesion surgery. The difference in body weight between the two groups continued to expand over the next four weeks. Six days postsurgery, the rats were bled (RBC's returned in 10% BSA-saline) every 15 minutes between 0600-1215 hr and growth hormone (GH) subsequently assayed. The total GH secretion, as computed from the area under each rat's ultradian pattern, was similar in both groups (DMN L versus SHAM, 2952.2 +/- 346.5 versus 2950.4 +/- 337.5). Using the PULSAR computer program, the baseline secretion (12.2 +/- 4.0 versus 11.8 +/- 2.7 ng/ml), total number of peaks (2.4 +/- 0.4 versus 2.4 +/- 0.2), and interpeak interval (2.8 +/- 0.5 versus 2.7 +/- 0.4, hr) were not significantly different between the DMN-L and SHAM rats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602471 TI - Puberty-affecting synthetic analogs of urinary chemosignals in the house mouse, Mus domesticus. AB - Endocrinologically- and socially-dependent volatile constituents of female mouse urine, identified in a previous study, were tested for their capability to accelerate puberty and extend the estrous period in young females. Several volatile ketones advanced puberty by approximately three days and extended the period of vaginal cornification in 55-75% of exposed females. High High concentrations of these substances were capable of overriding the known puberty delaying chemosignals. Volatile cyclic enol ethers were also effective in extending estrus, but not puberty acceleration. PMID- 2602472 TI - Dissociation of hypothalamic effects on ultrasound production and copulation. AB - Two studies were conducted to compare the brain mechanisms for copulation with those controlling other sexual behaviors, such as the ultrasonic calls that help hamsters and other rodents attract potential mates. Specifically, male and female golden hamsters were castrated and hormone-primed prior to being observed for rates of ultrasound production and levels of sex-typical copulatory behavior (mounts, intromissions and ejaculations in males; lordosis in females). Such tests were conducted before and after subjects received sham operations or bilateral lesions of the preoptic area (POA), anterior hypothalamus (AH) or ventromedial hypothalamus (VMN). The results confirmed previous work in showing the POA lesions decrease rates of intromission, ejaculation and ultrasound production, while VMH lesions decrease lordosis duration. More surprising was the tendency of VMN lesions to increase rates of ultrasonic calling by both males and females. For males, these effects identify differences between the neural circuits controlling copulatory and noncopulatory sexual behaviors. For females, they suggest a mechanism for the behavioral incompatibility of ultrasound production and lordosis. In particular, they raise the possibility that the suspension of ultrasonic calling that normally accompanies lordosis reflects an increase in VMN activity that simultaneously provokes lordosis and inhibits vocalization. PMID- 2602473 TI - Cardiovascular and sympathetic nervous system responses to an acute stressor in borderline hypertensive rats (BHR). AB - The present study examined cardiovascular and plasma catecholamine responses to acute footshock stress in adult male Wistar-Kyoto (WKY) normotensive, borderline hypertensive (BHR), and spontaneously hypertensive (SHR) rats. Basal mean arterial pressure and heart rate were equivalent for SHRs and BHRs, and levels for both groups were elevated compared to WKYs. Following transfer to the footshock chamber, blood pressure increased to a greater degree in SHRs than in WKYs or BHRs. However, the tachycardia was exaggerated in both BHRs and SHRs compared to WKYs. In response to intermittent footshock stress, all groups had comparable heart rate increases while maintaining blood pressure near baseline levels. SHRs demonstrated a sympathetic hyperresponsiveness to footshock stress, with greater increases in plasma norepinephrine and epinephrine levels than WKYs immediately following footshock. At 5 minutes postfootshock, plasma catecholamines remained elevated in SHRs over both WKYs and BHRs. Plasma catecholamine increases following footshock were comparable at all time points between WKYs and BHRs. The present results demonstrate that sympathetic responsiveness of BHRs to acute footshock stress is more similar to normotensive WKYs than to hypertensive SHRs. PMID- 2602474 TI - Hypothermia impairs performance in the Morris water maze. AB - Fifteen rats were trained to learn the location of a spatially fixed platform hidden in a Morris water maze (14-16 degrees C). Asymptotic performance was achieved over six training days (10 trials/day). Then retention of the task was assessed immediately after lowering core body temperature (Tc) to 28 degrees or 30 degrees C or stabilizing at 37 degrees C (the normothermic control). The hypothermia treatment order was counterbalanced according to a Latin-square design. Hypothermia significantly impaired all measures of spatial performance. Hypothermic animals were then rewarmed in a 40 degrees C water bath to 37 degrees C Tc and spatial performance tested again. Artificial rewarming resulted in complete recovery of all measures of spatial performance. These results demonstrate that hypothermia impairs performance in the Morris water maze, possibly by an amnesic mechanism, and that returning Tc to normothermic levels initiates recovery of performance. PMID- 2602475 TI - Inhibition of male sexual behavior by serotonin application in the medial preoptic area. AB - The study investigated the possible involvement of serotonin in the medial preoptic area in the regulation of sexual behavior of male rats. Injection of serotonin in the medial preoptic area resulted in an inhibition, whereas cyproheptadine (a serotonin antagonist) produced a slight facilitation, of male sexual behavior. PMID- 2602476 TI - Gender differences between the effect of monosodium glutamate on food intake in rats. AB - Monosodium glutamate (MSG) was recently reported to increase feeding in ad lib. fed rats [Reddy et al.(4)]. In the present study the responses of male and female adult rats to subcutaneous (SC) administration of MSG were compared. In female rats MSG 3 g/kg did not significantly affect food or water intake as compared with SC NaCl 0.9%; MSG 6 g/kg significantly reduced food intake but increased water intake. On the contrary, in male rats MSG 6 g/kg significantly increased food and water intake. It is concluded that there are differences between genders of rats in what concerns the effect of glutamate on food intake. PMID- 2602477 TI - Pre- and postpuberal medial preoptic area lesions and maternal behavior in the rat. AB - The ability of female rats to express maternal behavior following pre- or postpuberally-administered lesions of the medial preoptic area (MPOA) was investigated. Female Sprague-Dawley rats were electrolytically or sham-lesioned at either 28-30 days of age or 65-70 days of age and housed together in groups of 6-8 in "enriched" environments. Subsequently, the animals were mated and moved to individual cages just prior to parturition. Indices of maternal proficiency included nest ratings, pup retrieval time, percentage of pups with milk in their stomachs, and percentage of pup mortality. All animals in which lesions had substantially damaged the MPOA demonstrated significant deficits in all indices. Age at which the lesion was administered had no effect. In contrast to the recovery of male sexual behavior that has been reported for rats following prepuberally administered MPOA lesions, no recovery of maternal behaviors was seen in this study. Reasons for this lack of recovery may include the greater complexity of physiological and behavioral processes involved in maternal behavior in comparison to the rather stereotypical response patterns of male sexual behavior. PMID- 2602478 TI - Wulst lesions in pigeons disrupt go/no-go reversal. AB - Pigeons with lesions of either the Wulst or ectostriatum were compared to controls on reversal of a go/no-go pattern discrimination. The Wulst-lesioned animals were slower to acquire the response to the new S+ but were not different from the other groups on extinction of response to the old S+. The ectostriatum lesioned group was not different from controls. The results extend the range of situations in which Wulst-lesioned pigeons have been found to show a reversal deficit and are consistent with the notion that Wulst lesions may disrupt learning. PMID- 2602479 TI - Epilepsy and behaviour of the Mongolian gerbil: an ethological study. AB - Ethological procedures were used to compare behaviour characterizing seizure sensitive and seizure-resistant gerbils and to examine motor components of their major convulsions. Seizure-sensitive gerbils showed less social investigation when encountering an unfamiliar resident than their seizure-resistant counterparts. Sequence analysis showed the motor components of major seizures to segregate into three largely independent groups comprising elements associated with clonic-tonic spasms, with subsequent extensor immobility and with returning abnormal activity which preceded the resumption of normal behaviour. In grade 4 and 5 convulsions, the motor components of clonic-tonic spasms included the elements "rigid upright posture," "foreleg treading," "fall over," "mouth spasms." Straub tail and opisthotonus which were not seen in grade 3 seizures. The durations of clonic spasms and extensor immobility were longer in seizures of grades 4 and 5 than in those of grade 3. The abnormal motor activity following extensor immobility was complex and unrelated to seizure severity. It is suggested that observational studies in epilepsy may contribute to our understanding of the underlying pathophysiological processes. PMID- 2602480 TI - A test of Raibert's symmetry equations in animal and human running. AB - Based upon his work with robots, Raibert proposed that a specific class of symmetry equations may be important to animals and humans during steady-state running. In a test of this hypothesis, Raibert found good agreement with his predictions. However, his test was limited to one cat at two speeds and a human at a single speed. For the present study, we duplicated Raibert's methodology and tested his predictions for three cats, two monkeys, and a human at a variety of speeds. Our results indicate that body and limb movements in animals and humans generally are not in agreement with predictions based on the symmetry equations. PMID- 2602481 TI - Forebrain norepinephrine involvement in selective attention and neophobia. AB - It has been reported that depletion of forebrain norepinephrine via 6 hydroxydopamine infusion into the dorsal bundle decreases the rat's ability to selectively attend to relevant stimuli and thus increases the rat's responsiveness to novelty. In this study we measured 6-hydroxydopamine lesion effects on 1) selective attention via the nonreversal shift task and extinction of continuous reinforcement bar pressing and on 2) neophobia via consumption of a novel solution in a familiar environment; exploratory behaviors and consumption of a familiar food in a novel environment; and consumption of familiar and novel foods in a novel environment. Our data do not support a role for the dorsal bundle in selective attention. Our data do support a role for forebrain norepinephrine in neophobia and suggest that the lesion effects on neophobia result from an interaction between novelty of environment and novelty of food. PMID- 2602482 TI - Preference conditioning by concurrent diets with delayed proportional reinforcement. AB - Mildly food-deprived rats were presented at the same time either high- and low carbohydrate diets or protein-containing and nonnutritive diets differing in flavor in parallel with nutrient composition. After a few days of these concurrent 10-minute presentations, the rats preferred the flavor of the richer or nutritive diet. Such preference conditioning also occurred when there was a 10 minute delay between the presentation of two flavors in nonnutritive diet and intubation of a mixture of nutrients in proportion to the flavor intakes. Thus, rats are able to perceive the difference between the nutritional aftereffects of two distinctive diets presented concurrently and to learn to respond differentially to associated flavors even when there was a delay as long as that used in earlier studies with pyloric closure. Therefore, the reinforcement that has been suggested to arise from gastric chemoreception can be attributed instead to delayed postgastric effects. PMID- 2602483 TI - Pheromonal emission by pregnant rats protects against infanticide by nulliparous conspecifics. AB - The present studies of experiments focuses on infanticide in the nulliparous rat and asks two questions. First, what do infanticidal nulliparae gain from killing unrelated young? And second, does the recently parturient female have an effective strategy to counter female infanticide? With regard to the first question, we show two benefits from killing unrelated young, namely, that the killer utilizes the young as a food resource and that she occupies the nest site of the mother whose young she has destroyed. With regard to the second question, we show that an extended period of cohabitation with a pregnant female reduces the incidence of infanticidal behavior in nulliparae. Additionally, we demonstrate that the mother emits a pheromone during pregnancy which in itself reduces the incidence of infanticide and, in fact, often makes potentially infanticidal females maternal. The possible endocrine basis of this induced maternal behavior is discussed. PMID- 2602484 TI - Behavioral and endocrine consequences of heterosexual pair formation in squirrel monkeys. AB - The South American squirrel monkey (Saimiri sciureus) typically lives in large social groups containing several individuals of all age/sex categories. When living in established heterosexual pairs, reproduction in this seasonally breeding primate is poor. We attempted to induce breeding activity in pair-housed monkeys by forming new heterosexual pairs just prior to the breeding season. Breeding readiness, as reflected in behavior and gonadal hormones, was induced in males, but not in females. Males also showed persistent increases in cortisol levels following formation of new heterosexual pairs; females did not. The results indicate that social stimulation provided by a single novel female is sufficient to enhance breeding readiness in male squirrel monkeys. Females, on the other hand, are apparently unresponsive to a single male whether novel or familiar; this may account for the poor reproductive success in squirrel monkeys housed in heterosexual pairs. PMID- 2602485 TI - Acid and NaCl self-adaptation with micro-drop stimulation of fungiform papillae. AB - A small drop of either citric acid, HCl, or NaCl, judged to be approximately equal in magnitude, was applied to two papillae for a fixed duration (15 sec). The stimulus was then reapplied to the same papillae and judged for magnitude of sensation ("self-adaptation" design). NaCl was about 50% less intense after 15 sec of prior exposure whereas citric acid showed no significant decline and HCl showed either no decline or a significant increase in magnitude. When citric acid was tested with a longer exposure time (55 sec), significant decline in citric acid magnitude occurred for all subjects. These outcomes are discussed with regard to the problem of cutaneous irritation caused by certain stimuli and the difficulty of extracting cutaneous sensations from the sensory experience of strong concentrations of acids and salts. PMID- 2602486 TI - Medial accumbens lesions attenuate testosterone-dependent aggression in male rats. AB - Male hooded rats were castrated and implanted with testosterone-filled Silastic tubes appropriate for maintaining a normal average serum testosterone concentration. They were then given lesions of the medial accumbens nucleus or sham lesions. Twenty-four hours postoperatively each male was housed with a female. Beginning 7 days following pairing and continuing once each week for 4 weeks, each lesioned or sham-lesioned male was observed for aggression toward an unfamiliar male intruder. On the day following each test of aggression toward an unfamiliar male, each lesioned and sham-lesioned male was assessed for defensiveness toward an experimenter. Rats with medial accumbens lesions displayed significantly less aggression toward an unfamiliar male intruder during each of the weekly tests than did sham-lesioned animals. The attenuation was most pronounced in animals with lesions damaging the posterior part of the medial accumbens nucleus (also designated as anterior portion of the bed nucleus of the stria terminalis) in the region of the crossover of the anterior commissure. Although medial accumbens lesions are known to make individually housed rats hyperdefensive toward an experimenter, lesion-induced hyperdefensiveness was not observed in the pair-housed animals in the present experiment. It is argued that the medial accumbens/bed nucleus of the stria terminalis area is an important region in the anterior forebrain for the modulation of hormone-dependent aggression. PMID- 2602487 TI - Repeated noninvasive measurement of gastrointestinal transit in rats. AB - A technique for repeated and noninvasive measurement of oro-cecal transit time in rats and other small animals is described. It is based on the incomplete digestion of carbohydrates such as lactose fed orally to the animals. Since the activity of the enzyme lactase is low in almost all species, lactose is fermented by colonic bacteria after it arrived in the cecum, thus producing hydrogen. Hydrogen is delivered to the lungs via the circulation and exhaled by the animal. An increase in breath hydrogen measured by means of an electrochemical cell or a gas-chromatograph indicates the arrival of the nutrient bolus in the cecum. The method can be used repeatedly in individual animals under various experimental conditions such as investigations of stress effects on gastrointestinal transit. PMID- 2602488 TI - REM sleep modifications following a Morse code learning session in humans. AB - Various experimental data indicate that rapid eye movement (REM) sleep is involved in learning processes. In animals, any complex task in a learning environment leads to an increase of the consecutive total REM sleep time, especially just before learning completion. In humans, the oculomotor activity during REM sleep seems to constitute an interesting marker of learning performance. In this work, we focus on the qualitative analysis of REM sleep characteristics after a Morse code learning session. Eight male subjects were polygraphically recorded during three consecutive nights. A computer aided teaching session was performed just before bedrest onset of the experimental night. The learning performance (percentage of saving) was checked on awakening. The Morse code learning led to some modifications in REM sleep components, particularly increases of REM sleep time and number of REM episodes. We did not observe any significant modification in the total number of REMs in the experimental night. However, the correlative analysis between learning performance and sleep parameters indicates a superior r for the oculomotor activity than for the tonic components. This is consistent with the information processing hypothesis in which the temporal distribution of REMs reflects the subject's ability to increase the signal-noise ratio from environmental information intake. PMID- 2602489 TI - Hepatic-portal and cardiac infusion of CCK-8 and glucagon induce different effects on feeding. AB - In order to compare effects of circulating CCK-8 and glucagon on food intake, rats were provided with a permanently implanted catheter in the right atrium. Another cannula was implanted into the hepatic-portal vein by a new technique. After a standard fasting period graded loads of CCK-8 and glucagon were infused via these catheters during refeeding. Intracardiac glucagon and CCK loads dose dependently suppressed meal size. Intraportal infusion of glucagon caused similar suppression compared to intracardiac administration. This may indicate a minor role of the liver as a target for the suppression of feeding by glucagon. In contrast, intraportal infusion of CCK-8 did not reduce food intake. The results indicate that CCK-8 is removed or inactivated by the liver. It is suggested that CCK-8 acts locally on vagal nerve endings to exert its suppressive action on food intake. PMID- 2602490 TI - The effect of human chorionic gonadotropin on serum levels of testosterone, estradiol, and sexual behavior in young and old rhesus males. AB - Sexual behavior and serum levels of testosterone (T) and estradiol (E) were examined in five young and six old rhesus males (Macaca mulatta) before and after the injection of 500 and 1000 IU of HCG. The serum levels of T and E increased in both young and old males after injection of either dose of HCG. Serum levels of T were significantly higher in young than in old males in the period following the last injection of 1000 IU of HCG. Old males had significantly higher levels of serum E during treatment with 1000 IU of HCG, but serum E levels in the two groups did not differ before or after treatment. Serum levels of T and E did not differ between the young and old males when injected with 500 IU of HCG. HCG had no effect on sexual performance and the differences in levels of sexual performance between the young and old males were not eliminated. PMID- 2602491 TI - Stimuli of thirst in donkeys (Equus asinus). AB - A study of the stimuli of thirst was conducted on six feral donkeys. Donkeys were found to be stimulated to drink by overnight water deprivation, by the diuretic furosemide, and by hypertonic saline infusion, all in the absence of heat stress or work. Donkeys compensate accurately for the fluid deficit caused by overnight water deprivation. After 19 hr without water, they drank 8.8 +/- 2.4 (mean +/- SE) liters within 60 min. Their undeprived overnight intake was 8.4 +/- 1.5 liters. However, latency was longer and water intake was less than that of ponies with the same changes in blood parameters, suggesting that donkeys have a higher thirst threshold than ponies. Further, plasma volume fell less in donkeys, but osmotic changes were similar to those reported in ponies exposed to the same deprivation. Donkeys infused with 250 ml of 15% NaCl drank 0.7 +/- 0.6 liters of water within 45 min, and osmolality increased from 287 to 297 mosmol/kg water; they drank no water in the same time period when infused with 250 ml 0.9% NaCl (p less than 0.05). Donkeys injected IV with 2 mg/kg furosemide drank 3.8 +/- 1.1 liters within 3 hr. Plasma protein increased from 6.9 to 7.8 g/dl. When injected with 0.9% NaCl they drank 1.0 +/- 0.5 liters (p less than 0.05). In sum, the positive thirst responses of these donkeys to cellular and extracellular dehydration were similar to those earlier demonstrated in ponies, but the results suggest a less sensitive response, albeit combined with a better internal defense of blood volume. PMID- 2602492 TI - Phase-response curve to 1-hour light pulses for the marsupial, Dasyuroides byrnei. AB - Most Australian marsupials are nocturnal and consequently it might be expected that the circadian system of this group may be similar to the circadian system of nocturnal rodents. Ten male kowaris (Dasyuroides byrnei) were allowed to free-run in constant darkness and were subsequently administered 1-hour light pulses (1000 lux) at known circadian times in their cycles at intervals of greater than 2 weeks. Changes in the phase of the kowari's circadian rhythm of wheel-running were measured when their rhythms reached a new steady-state after each light pulse and these data were used to construct a phase-response curve to light for the species. The kowari PRC exhibited essentially the same characteristics as those reported for the nocturnal rodents and the marsupial species Sminthopsis macroura. It appears that the kowari entrains its circadian rhythms to light/dark cycles via the discrete phase shifting mechanism as described in nocturnal rodents. PMID- 2602493 TI - Hepatic vagotomy increases consumption of a novel-tasting diet presented immediately after surgery. AB - To further characterize the possible effect of hepatic vagotomy on food intake, rats adapted to a medium-fat diet (MF diet) were offered a novel-tasting diet immediately after hepatic branch vagotomy (HBX rats) or sham vagotomy (SHAM rats) and food intake as well as diet selection (novel-tasting vs. familiar diet) was measured. When a novel-tasting sweet medium-fat diet (SMF diet) was offered immediately after surgery, HBX rats ate transiently more (days 1-4 after surgery) and selected more (days 5 and 6 after surgery) of the SMF diet than SHAM rats. Similar results were obtained when a novel-tasting bitter diet (AMF diet) was offered instead of the SMF diet. In contrast, when rats adapted to the AMF diet prior to surgery were given normal MF diet as novel-tasting diet immediately after surgery, HBX and SHAM rats' postoperative food intake and diet selection did not differ. When rats were given only MF or SMF diet before and after surgery, HBX and SHAM rats' food intake during the initial postoperative period also did not differ. The results indicate that hepatic branch vagotomy and sham vagotomy have different aversive effects which lead to transient differences in postoperative food intake when diets with a novel and strong taste are presented during the initial postoperative period. Therefore, information conveyed by the hepatic branch of the vagus can apparently lead to a conditioned feeding response. This is evidence for a more subtle role of the liver in the control of food intake than previously thought. PMID- 2602494 TI - The effects of capsaicin on emotional responses to odors in the rat. AB - Capsaicin is described as disturbing the autonomic responses to stress-inducing environments. The effects of capsaicin (130 mg/kg in 2 series of subcutaneous injections) on emotionality responses were studied in 19 Sprague-Dawley male rats using the open-field test. Eleven rats treated with isotonic saline served as controls. Emotionality (E) measured before capsaicin treatment in the open-field ventilated with deodorized air was similar in the 2 groups of rats. Nine out of the 19 treated rats survived. Their E was significantly higher than that of there 10 rats that died from capsaicin. When a frightening odor (fox feces) was added to the open-field E increased in the controls but remained unchanged in the capsaicin-surviving rats. The ability to discriminate palatable food or female odor was similar in the two groups. The results suggest that; 1) Highly emotional rats survived subcutaneous capsaicin injections; 2) Reaction to an emotionality inducing environment was decreased in the capsaicin-surviving rats; 3) Olfactory discrimination was not impaired by capsaicin treatment. PMID- 2602495 TI - Lack of diet-induced thermogenesis following lesions of paraventricular nucleus in rats. AB - The effects of electrolytic lesions in the hypothalamus paraventricular nucleus were studied in adult male and female Sprague-Dawley rats, fed different diets, consisting of either palatable human food plus chow (cafeteria diet) or chow alone. The results showed that both cafeteria diet and lesions induced an increase in energy intake and weight gain in rats of both sexes. Oxygen consumption rate and colonic temperature were significantly decreased by lesions, while cafeteria diet increased the same parameters only in intact animals. The lesion decreased weight, protein and DNA, and temperature of brown adipose tissue, while cafeteria diet increased the values considered in brown adipose tissue of sham-injured rats, but not in lesioned animals. The response to norepinephrine administration was significantly greater in intact rats and those fed cafeteria diet. The results suggest that the larger body weight gain observed in lesioned rats, particularly evident in rats fed cafeteria diet, is partly due to the disappearance of diet-induced thermogenesis that depends on the reduced mass and functional activity of brown adipose tissue. PMID- 2602496 TI - No influence of adrenalectomy on measures of taste sensitivity in the rat. AB - The influence of adrenalectomy on the taste sensitivity and responsivity of Long Evans rats to sodium chloride and sucrose tastants presented separately and in mixtures was examined using high precision gustometry, computer-controlled go/no go operant procedures, and nonparametric signal detection measures. Relative to baseline levels, adrenalectomized rats' plasma corticosterone levels decreased by 328% while sodium chloride and water consumption increased by 548% and 165%, respectively. The same measures remained unchanged in sham-operated animals. Taste sensitivity and responsivity to sodium chloride and sucrose did not differ between adrenalectomized and sham-operated animals and discrimination performance remained the same between the groups as well. The present results support and extend previous findings that adrenalectomy and the resultant corticosteroid deficiency does not influence taste sensitivity or responsivity in the rat. PMID- 2602497 TI - Telencephalic function implicated in food-reinforced color discrimination learning in the goldfish. AB - The effects of telencephalic ablation on the learning of color discrimination were studied in the goldfish (Carassius auratus) to determine the role of the telencephalon in the learning. The performances of normal and telencephalonless animals were compared in relation to their instrumental training rates. The animals were trained to discriminate between blue and green stimulating patches presented simultaneously. Normal and telencephalonless animals which underwent ten trials per day were unable to discriminate between the stimuli, but animals which underwent thirty trials showed learning. In animals which underwent twenty trials, there was a clear difference between the performances of normal and telencephalonless animals: the normal ones were able to learn, but the telencephalonless ones showed a significantly impaired learning ability. These results suggest that the telencephalon is not essential for the learning, but is supplementary in that it facilitates integration of neural events in extratelencephalic areas that are necessary for the instrumental process involved in color discrimination learning. PMID- 2602498 TI - The ventromedial nucleus of the hypothalamus outputs long-lasting running in rats. AB - We have developed a new technique for altering neural construction by implanting self-swelling, the hydrogel of water-absorbent polymer (WAPGEL) into restricted areas of the brain. Using this technique, we found that the VMH is responsible for expression of running activity. Implantation of 1.5 microliters of WAPGEL into the dorsomedial portion of the ventromedial nucleus of the hypothalamus (VMH) of the rat specifically induced bursts of running, whereas implantation into other sites of hypothalamus, e.g., the anterior, lateral and posterior areas, and the dorsomedial nucleus, caused no significant running activity. The WAPGEL-injected rat showed less aversive reactions than the sham-operated rat. Since deafferentation of the VMH after WAPGEL injection prevented the induction of running activity, the output from the VMH appeared to be responsible for the running activity. PMID- 2602499 TI - Effects of site-specific CNS microinjection of cholecystokinin on lordosis behavior in the male rat. AB - We have previously demonstrated that intracerebroventricular injections of sulphated cholecystokinin octapeptide (sCCK-8) had a dramatic facilitatory effect on lordosis behavior in the gonadectomized, estrogen-primed male rat. In the female, sCCK-8 facilitates or inhibits lordosis when microinjected into the medial preoptic nucleus (MPN) or ventromedial nucleus of the hypothalamus (VMH), respectively. In order to identify sCCK-8 responsive sites that modulate lordosis behavior in gonadectomized males, sCCK-8 was microinjected into the MPN or VMH. Sulphated CCK-8 significantly increased lordosis behavior when microinjected into the MPN of estrogen-primed males, but had no significant effects when microinjected into the VMH. These results imply that CCK-sensitive neural substrates within the MPN may act to disinhibit lordosis in the gonadectomized, estrogen-primed male rat. The lack of an effect of VMH injection of sCCK-8 on lordosis in males is discussed in terms of possible sex differences in sCCK-8 sensitive lordosis-modulating circuits. PMID- 2602500 TI - Entrainment of anticipatory activity to various durations of food access. AB - Rats with lesions of the suprachiasmatic nuclei (SCN) and intact rats were maintained on restricted feeding with the duration of food access ranging from 4 to 12 hr. All rats with SCN lesions displayed at least some anticipatory activity (AA) at all food access durations. The amount of AA diminished when food access was extended to 12 hr and was lowest in a group that was exposed only to a 10-hr access period. The onset of AA (phase angle of entrainment) appeared to be more sensitive to the time of food availability than to its termination. Most intact rats maintained in constant light displayed some AA at food access durations between 4 and 10 hr. In most cases the period of the free running rhythm increased as it crossed food access and the free running rhythm became increasingly disrupted as the experiment progressed in all rats. In some cases the free running rhythm appeared to force AA out of entrainment. These results demonstrate that AA occurs in conditions that impose only minor deficits on the energy balance of rats. Furthermore, they provide additional evidence of interactions between two separate circadian pacemaking systems. PMID- 2602501 TI - Feeding regime affects activity-stress ulcer production. AB - Rats were divided into either an active group housed in activity wheels or a control group housed in stationary laboratory cages. Both active and control groups were further divided into groups receiving 1, 2, 3, or 4 meals daily for a total feeding time of 1 hr. Control rats were food-yoked to active animals. Results indicated that active rats fed 1 meal daily developed significantly more ulceration, lost more weight, and consumed less food and water than other groups. The number of daily meals had no effect on the amount of activity. No control animals developed ulcers, although they received the same amount of food. These results suggest that frequent feedings mitigate gastric peptic ulcer formation in rats placed in the activity-stress ulcer paradigm. PMID- 2602502 TI - Behavior and heart rate of heifers housed in tether stanchions without straw. AB - The effect of tether housing without straw was studied in eight heifers over a 12 week period. Resting behavior was recorded in the first and the twelfth week and heart rate (HR) in the twelfth week and compared to that of eight control heifers kept in a group on deep straw. Tethered heifers changed body position from standing to lying and vice versa significantly less often, and frequency of lying intention movements prior to lying down was significantly increased in tethered heifers. Correspondingly, latency between first intention movement and actually lying down was markedly increased in tethered heifers. HR was significantly higher in tethered heifers in all situations studied. During the lying procedure, HR increased in all animals so that the difference between the two groups remained unchanged. The biggest difference between groups was measured during the first lying intention, when HR was 125.2 +/- 9.4 in tethered heifers and 76.8 +/- 6.1 in controls. The results indicate that lying down in tether stanchions is aversive to the heifers and avoided as much as possible. PMID- 2602503 TI - Vasopressin-deficient rats show a reduced amplitude of the circadian sleep rhythm. AB - The hypothalamic suprachiasmatic nuclei are responsible for the generation of many circadian rhythms, including the rhythm of arginine vasopressin (AVP) in the cerebrospinal fluid (CSF). We used cortical EEG recordings taken from AVP deficient (Brattleboro strain) rats to investigate the possible role of AVP in the generation of circadian sleep/arousal rhythms. When housed either in a light dark cycle or in constant light, Brattleboro rats showed circadian rhythms of arousal, slow-wave sleep, and paradoxical sleep. However, the amplitudes of the slow-wave and paradoxical sleep (but not arousal) rhythms in these animals were significantly lower than in controls. The results indicate that hypothalamic synthesis of AVP is not necessary for the generation of circadian sleep rhythms, but the amplitude of the rhythms may be modulated by the circadian release of AVP into CSF. PMID- 2602504 TI - Nucleus basalis magnocellularis lesions facilitate two-way active avoidance. AB - Bilateral ibotenic acid lesions of the nucleus basalis magnocellularis (NBM), which resulted in 30% depletion of cortical choline acetyltransferase, facilitated acquisition of shuttlebox two-way active avoidance learning in rats. These results contrast with a report of impaired two-way active avoidance after bilateral electrolytic lesions of the NBM, but support findings of facilitation after ibotenic acid lesions. The data suggest that electrolytic lesions impair shuttlebox learning by damaging fibers of passage in the vicinity of the NBM. PMID- 2602505 TI - Increased locomotor activity of rats by self-stimulation in a running wheel. AB - A method was developed in which the intracranial self-stimulation of rats was dependent on their locomotor activity. During each rotation of a running wheel (= 0.75 m), six stimulus trains were administered via electrodes in the medial forebrain bundle. Under these conditions, animals increased their locomotor activity 112-fold, compared to a control condition without self-stimulation. This method may be a valuable procedure in various research fields where extreme increases in motor activity of laboratory animals are advantageous. PMID- 2602506 TI - Voluntary ethanol consumption during pregnancy and lactation in the golden hamster. AB - Golden hamsters voluntarily consume substantial amounts of ethanol without developing dependence, apparently because ethanol metabolism is rapid and efficient. Six adult female hamsters were given continuous free access to Purina chow, water and a 20% (v/v) ethanol solution before and during pregnancy and during lactation; six control females did not receive the ethanol solution. Intakes of food and water were not elevated during pregnancy, but increased markedly for both groups during lactation. Ethanol consumption remained substantial but unchanged throughout the experiment, with ethanol consumers taking an average of 3.8 g (4.4 kcal) of ethanol solution daily. No significant differences were observed in the size and weight of litters either at delivery or at 16 days postpartum. PMID- 2602507 TI - [An infant's "forbidden games" (related to six cases of severe merycism)]. AB - Merycism (pondering, in Anglo-Saxon Literature) is an affectation that has become rare in infants but which is still news because of its potential severity. Although psychosomatic by nature, it compromise the vital prognosis if the diagnosis isn't made and appropriate psychotherapeutical measures taken in good time. Based on six cases of severe merycism, the author studies the sign-language and the diagnostic in order to specify the positive elements that must have brought about the illness. A psychopathological hypothesis of the aberrant behavior leading to this "heavy thinking" is put forth. The various psychopathological mechanisms at play in this problem are then shown based on how frustratingly isolated the baby is. Finally, treatment by intensive nurturing and its behavioral components is described as well as the evolution to a half-way point. The ending goes back to the affective meaning of the problem. PMID- 2602508 TI - [The psychotic component of so-called normal parents]. AB - Working with very young children who are placed, on a part-time basis, in a facility affording associated psychoanalytical treatment, points up special parent-child relationships. For children showing personality structures of a psychotic nature, these relationships coincide with the psychic core of the parent's personality structure. This is a very real pathological "meeting of the minds" that partoof the therapeutic treatment is based on. PMID- 2602509 TI - [The child as a substitute]. AB - The feeling of temporarily not being oneself is a common phenomenon, with many manifestations in normality and psychopathology. I relate it here to the Freudian category of the uncanny (das Unheimliche) and to the literary device of the double (der Doppelganger) and I consider the splitting in the ego and the distortion of the sense of identity to be their main psychological characteristics. An extreme instance of this phenomenon is represented by the replacement child, that is a child conceived with the conscious purpose on the part of its parents of substituting a dead sibling. Replacement children inevitably suffer from a sense of confusion in the area of self-identity and often display serious difficulties in the development of self-esteem and in the establishment of mature object-relationships. As illustrations of some of the problems encountered by replacement children, I briefly refer to the experiences of two great artists (Van Gogh and Dali) and I use clinical material from two of my psychoanalytic patients. PMID- 2602510 TI - [Recovering from a lag in psychological development after harmful environmental factors have been eliminated]. AB - This paper reports the long term effects of deprived environments and the possibility of recovery from delays in psychological development after removal of perturbing influences. Two groups of children who had suffered from deprivation with either low IQ (76 for G I) or high IQ (112 for G II) towards the age of 7 have been reared in a private permanent foster care (the SOS children's villages) after family rupture. They have been reassessed between 5-10 years during adolescence (IQ, school attainment, behaviour). Results are compared with those of children with identical IQ still leaving in their deprived homes or under care in traditional foster care families. Thanks to the ecological and environmental change recovery is possible particularly from cognitive delays; behaviour problems need much more time to decrease or to disappear. Age at placement exerts differential effects according to the developmental processes in action (intelligence, behaviour). PMID- 2602511 TI - Annual NCDEU meeting 1989. Abridged proceedings. 28th annual meeting of the New Clinical Drug Evaluation Unit. May 31-June 3, 1988, Key Biscayne, Florida. PMID- 2602512 TI - The negative symptom assessment: a new instrument to assess negative symptoms of schizophrenia. PMID- 2602513 TI - Diagnostic criteria and behavior patterns in infantile autism. PMID- 2602514 TI - Alprazolam intolerance in stable schizophrenic outpatients. PMID- 2602515 TI - Drug response assessed by the Modified Maudsley Obsessive-Compulsive Inventory. PMID- 2602516 TI - Investigating drug plasma levels and clinical response using random regression models. AB - The reanalysis of the Riesby dataset using a random regression model indicates a significant effect of DMI plasma measurements on HAM-D scores across the four timepoints of the study. This effect is especially strong when the HAM-D change from baseline score is used in place of the actual HAM-D score at the four timepoints. A significant effect of IMI was not found for either the actual HAM-D score or the HAM-D change from baseline score. An endogenous effect was marginally significant when the actual HAM-D score was used; however, this effect was not observed when the HAM-D change score was used as the dependent measure. There also was evidence of a marginally significant effect due to autocorrelation of the residuals, indicating that the residuals at a given timepoint were related to the residuals from previous timepoints according to a first-order autoregressive process. In contrast, when the repeated measures MANOVA was used to analyze these data, a significant effect of DMI was not observed, since subjects without complete data at all timepoints had to be dropped from the analysis. In longitudinal psychiatric studies where missing data are the rule (rather than the exception), the random regression approach provides an attractive alternative to the traditional methods of analyzing longitudinal data. PMID- 2602517 TI - A descriptive profile of the depressed child. AB - We have identified a number of basic descriptive features common to the prepubertal child (aged 6-12) who meets criteria for an objectively defined mood disorder in the inpatient psychiatric setting. Clinical and structured diagnostic interviews conducted with both the child and the parent revealed that DSM-III criteria for major adult mood disorders were easily met by the depressed children. The symptom profile for the child is similar to the adult profile: feelings of hopelessness, sadness, and despair; depressed mood; vegetative symptoms of low energy, appetite loss, and disturbed sleep; and quite frequently suicidal ideation and/or action. Noteworthy is the fact that most of the parents did not bring their children to the setting reporting that they (either themselves or the child) were depressed. The parent was most likely to focus on the change in school performance and on relationships with siblings or other family members (withdrawal, more fighting and irritability, anhedonia, etc.). In sum, our findings indicate that children with MDD tend to have family histories of psychiatric disorder, school problems, and psychosocial adjustment problems. We have also found IMI to be effective in treating the disorder (e.g., Hughes & Preskorn 1989; Preskorn et al. 1982, 1986, 1987). Thus, early diagnosis and effective treatment are possible. This conclusion raises the possibility that steps can be taken to prevent (or at least interrupt) the long-term sequelae (e.g., chronic dysthymia, impaired self-image, impaired psychosocial adjustment) of untreated depressive episodes in prepubertal children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602518 TI - Long-term followup of patients on managed lithium discontinuation. PMID- 2602519 TI - Response to clozapine in chronic psychotic patients. PMID- 2602520 TI - GM1 ganglioside as a potential treatment in tardive dyskinesia. PMID- 2602521 TI - Attention deficit hyperactivity disorder and methylphenidate: the relationship between gross body weight and drug response in children. PMID- 2602522 TI - Psychiatric diagnosis in Japan. 1. A study on diagnostic labels used by practitioners. AB - In a questionnaire survey, a list of 64 psychiatric diagnostic labels was presented to 20 randomly selected Japanese psychiatrists affiliated to a university department of psychiatry. For each label, they were asked (2) whether they used it in everyday practice, (b) whether they rarely used it but would do so if faced with such a case, or (c) whether they had never and would never use it. It was found that these Japanese psychiatrists used a relatively small number of diagnostic categories; in their classificatory system, functional mental disorders would be dichotomized into psychoses and neuroses with the former further divided into schizophrenic, atypical and manic-depressive psychoses, and the latter divided into seven subcategories, i.e., anxiety neurosis, hysteria, depressive neurosis, phobia, obsessive compulsive neurosis, depersonalization neurosis and hypochondriasis. PMID- 2602523 TI - Psychiatric diagnosis in Japan. 2. Reliability of conventional diagnosis and discrepancies with Research Diagnostic Criteria diagnosis. AB - Twenty Japanese psychiatrists were asked for their conventional diagnoses for each of 29 case vignettes already diagnosed according to Research Diagnostic Criteria. The reliability coefficients of Japanese conventional diagnoses were low; only two categories exceeded the intraclass correlation coefficient of 0.7. However, the low reliability was found to be due not to random variations but to the difference of individual psychiatrists in setting boundaries of diagnostic entities though sharing the common prototype for each diagnostic category. PMID- 2602524 TI - Delusional theme, sex and age. AB - In a retrospective study of 865 delusional syndromes, connections were investigated between delusional themes and the sex of patients, and the ages in which these themes extensively occurred. According to previous reports, the results of this investigation indicated that differences exist between the ages of manifestation regarding the themes of hypochondria, persecution, love and jealously. Furthermore, differences could be observed between males and females in relation to the frequency of choice of particular themes, as well as the age of occurrence. Based on psychological studies concerned with the content's dependence on motives we conclude that the age distribution of delusional themes corresponds to the main existential concerns in different life periods. PMID- 2602526 TI - Empirical coverage of psychodynamic configurations of anorexia nervosa. AB - For the last several years, the clinical picture of anorexia nervosa has been covered at the following three levels: (1) symptomatology (including partner and family relations); (2) psychodynamics; (3) narcissistic level. As far as the psychodynamic level is concerned, this paper presents the pertinent theory in its operationalized form for a clinical rating. The convergent validity of the five psychodynamic configurations is tested by a comparison of clinical rating, a questionnaire (IATAN) and a standardized interview (SIAN); divergent validity is tested by verifying the mutual differences of the five configurations. PMID- 2602525 TI - Psychopathology, temperament, and past course in primary major depressions. 2. Toward a redefinition of bipolarity with a new semistructured interview for depression. AB - We report on the utility of a new instrument to identify subtypes of major depressive episodes with special reference to pseudo-unipolar conditions. By incorporating reliable measures of depressive and hyperthymic temperamental characteristics in subtype definitions, we achieve the sharpest possible demarcation between unipolar and bipolar disorders. The new procedures also reveal that 1 out of 3 primary depressives in a consecutive series of 405 patients belong to the bipolar spectrum. Furthermore, among bipolars, bipolar II disorder (redefined as major depressions with hypomania or hyperthymic temperament) represents the most common variant. We discuss the nosologic, therapeutic, methodologic and theoretical implications of these considerations on the unipolar-bipolar dichotomy. Given that major depression emerges as the final common clinical expression of a heterogeneous group of disorders, it underscores the importance of focusing on temperament and course of illness in subclassification efforts such as attempted here. PMID- 2602527 TI - Body awareness group therapy for patients with personality disorders. 1. Description of the therapeutic method. AB - The aim of this paper is to describe the Body Awareness Group Therapy (BAGT) designed for patients with personality disorders. The BAGT is a body-oriented small group therapy conducted by a physiotherapist and a cotherapist. The aim is to foster personal growth and development by use of individual and group exercises. The therapy is a synthesis of earlier clinical experiences, mostly based on works of Reich, on elements of encounter and of eastern body tradition. PMID- 2602528 TI - Body awareness group therapy for patients with personality disorders. 2. Evaluation of the Body Awareness Rating Scale. AB - The Body Awareness Rating Scale (BARS) was developed to evaluate the treatment process of the Body Awareness Group Therapy. The BARS subscales proved to have high interrater reliability. A factor analysis revealed two factors which seemed to measure one awareness and one movement dimension. The BARS was sensitive to change. As hypothesized, the BARS improvement enlarged with increasing duration of treatment. At discharge the good BARS outcome patients had improved significantly more than the poor BARS outcome ones, both concerning symptoms and global psychopathology. PMID- 2602529 TI - Integrated psychotherapy in the project of the treatment of psychoses. AB - We present a model of integrated psychotherapy of schizophrenia. When we do an integrated therapy with a patient, attention must always be directed to the calibration of the interventions which constitute the therapeutic compound. This kind of calibration has to be done by a therapist with an integrative function. Experience and competence are necessary conditions, but not sufficient ones for carrying out such a function; the therapist must have also the authority which is due not only to his hierarchic role, but which has to be empathically recognized by the other therapists and the patient. The theoretical reflection has been possible only by starting from a clinical experience (the case of a young woman who in the light of the nosographical categories was considered an 'impossible patient') which allowed us to translate the clinical language into a conceptual form. PMID- 2602530 TI - Short psychotherapeutic interventions (four sessions). AB - This paper points out: (1) The fundamental importance, during the patient's first visit, of a shift of the objective involvement on the therapist's person, when a significant real object fails. (2) An initial interpretation, based on understanding this mechanism, is mutational in that it transfers the mourning for relations to internal objects. (3) The patient usually takes medical advice when in a more or less open crisis situation, where his objective investment (internal and external) is shaken. (4) The nature of the crisis can be understood, by a deep investigation of the patient's relational context following a psychoanalytical pattern. (5). Application of these concepts allows very short interventions (psychotherapeutic interventions), the therapeutic value of which is undeniable. PMID- 2602531 TI - Primary hyperparathyroidism, psychiatric manifestations, diagnosis and management. AB - Mental manifestations of primary hyperparathyroidism simulate a wide spectrum of psychiatric disorders. Definitive surgical treatment results in long-lasting full recovery. The 2 cases presented demonstrate this. The clinical diagnostic and therapeutic aspects of primary hyperparathyroidism, with an emphasis on neuropsychiatric manifestations, are discussed. Early diagnosis of hypercalcemia can prevent unnecessary and potentially harmful treatment with antidepressive, anxiolytic or antipsychotic drugs, which can further depress the cognitive state of the patients, and can aggravate the mental symptoms. PMID- 2602532 TI - Alexithymic characteristics in rheumatoid arthritis: a controlled study. AB - Forty rheumatoid arthritis (RA) patients diagnosed by rigid criteria were evaluated for alexithymic characteristics using the Beth Israel Hospital Psychosomatic Questionnaire (BIQ) and the Toronto Alexithymia Scale (TAS). 40 healthy subjects matched with RA patients on sociodemographic variables served as controls. RA patients scored significantly higher on the BIQ and TAS compared to controls. The two scales correlated in the expected direction. Using the TAS cutoff score of 74 and above, 11 RA patients (27.5%) were identified as alexithymic. RA patients with greater functional impairment showed significantly higher alexithymia scores. PMID- 2602533 TI - Alexithymia and breast cancer. Survey of 200 women undergoing mammography. AB - The Schalling Sifneos Personality Scale (SSPS) and the Middlesex Hospital Questionnaire (MHQ) have been used in 381 women just before mammography at the Breast Center of the Radiology Institute, University of Bari (Italy). Of the 200 women who accepted to complete the questionnaires 13 were found positive for cancer. Student's t test comparison of the mean SSPS and MHQ scores of the positive for cancer with the negative showed that women with breast cancer have more pronounced alexithymic but not neurotic traits. Our findings suggest that patients with cancer may have something in common with those suffering from so called psychosomatic pathologies who have a constrained imagination and fantasy and difficulty in verbalizing their emotions. Thus, this study indicates a relationship between alexithymia and cancer. PMID- 2602534 TI - An audit of doctor's management of patients with chest pain in the accident and emergency department. AB - In a series of 604 patients attending an accident and emergency department with chest pain, the decisions made by casualty officers about admission to the coronary care unit were compared with the retrospective opinions of experienced clinical assessors who knew the results of any subsequent investigations. Of the 119 patients whom the assessors judged should have been admitted to the coronary care unit, 14 (11.8 per cent) were judged to have been discharged in error. Of the 485 patients whom the assessors judged should not have been admitted to the coronary care unit, 32 (16 per cent) were judged to have been advised admission unnecessarily. Misinterpretation of the electrocardiographic results was apparently the reason for five of the 14 false negative errors and four of the 32 false positive errors. The median time that patients who were eventually admitted to the coronary care unit spent in the accident and emergency department was 78 min. PMID- 2602535 TI - Renal biopsy in patients with unexplained renal impairment and normal kidney size. AB - We report renal biopsy findings in 109 patients with unexplained renal impairment (serum creatinine greater than 0.15 mmol/l) and normal-sized non-obstructed kidneys. The most common histological lesions were interstitial nephritis, rapidly progressive glomerulonephritis and a variety of other types of glomerulonephritis. The groups could not be distinguished by the presence or absence of hypertension, haematuria, proteinuria, or features of systemic disease. However interstitial nephritis was found more frequently in patients presenting with one or none of these features and rapidly progressive glomerulonephritis in patients presenting with three or more. All four patients with none of these features had interstitial lesions. Fifty-two per cent of patients with interstitial nephritis improved and 60 per cent of the patients with rapidly progressive glomerulonephritis who received immunosuppressive treatment improved or remained stable with treatment. The benefits of a biopsy diagnosis were almost wholly confined to these two groups. Complications were recorded in nine patients - prolonged macroscopic haematuria in six and symptomatic perirenal haematomata in three. Six required blood transfusion. One required nephrectomy to control haemorrhage and subsequently died. Percutaneous renal biopsy is not without risk in patients with renal impairment but the benefits of diagnosing interstitial nephritis and rapidly progressive glomerulonephritis outweigh the disadvantages. PMID- 2602536 TI - Possible evidence for a variant of myasthenia gravis based on HLA and acetylcholine receptor antibody in Chinese patients. AB - A comprehensive study of 194 Chinese patients with myasthenia gravis in Hong Kong has shown distinct differences from the patterns of disease seen in Caucasians. Restricted ocular myasthenia is the predominant disease type in patients presenting in the first two decades of life and is associated with absence or low titres of acetylcholine receptor antibody. Predisposition to this type of disease is strongly associated with HLA-DRw9. Generalized myasthenia gravis occurs predominantly in patients presenting after the age of 20 years and is accompanied by high titres of acetylcholine receptor antibody but is less strongly associated with HLA-DRw9. It is suggested that myasthenia gravis occurring within the first two decades of life and characterized by affected ocular muscles and absence or low titre of acetylcholine receptor antibody is a genetically determined variant of the disease which occurs commonly in Orientals. PMID- 2602537 TI - Wilson's disease presenting with features of hepatic dysfunction: a clinical analysis of eighty-seven patients. AB - An analysis has been made of presenting symptoms and course in 87 patients with predominantly hepatic Wilson's disease. In 30 patients, in whom the diagnosis was made relatively quickly, response to treatment was excellent and all recovered although two had severe haemolytic crises. Mean age of onset was 11 years (range five to 22). Nine patients suffered toxic reactions to penicillamine and were then treated with trientine. In 22 patients the diagnosis was made after neurological symptoms had supervened; in 20 the signs of hepatic damage had disappeared despite the lack of treatment but in two hepatic signs persisted until the central nervous system was affected. In the 20 patients in whom signs of liver disease resolved spontaneously there was a time interval of from one to eight years before neurological signs developed. All 22 patients in a third group died of hepatic disease without central nervous system involvement. In 19 cases duration of the illness was brief and the diagnosis was made very late or at post mortem examination. One patient survived with chronic progressive liver damage for 20 years; diagnosis was also made at post-mortem examination. Mean age at death was 15 years. The diagnosis was made retrospectively in 13 patients who died. In two of these the diagnosis was confirmed by determination of the liver copper concentration on tissue saved at postmortem examination; in the other 11 the diagnosis is probable since other siblings developed a similar illness, proven to be Wilson's disease. Age range for these patients was eight to 13 years. Duration of the illness from onset to death was nine days to four years (mean 10 weeks). There was no example of primary carcinoma of the liver in this series. PMID- 2602538 TI - The prevalence of hyperlipidaemia and related clinical features in insulin dependent diabetes mellitus. AB - The prevalence of hyperlipidaemia and related clinical features was examined in 205 individuals with insulin-dependent diabetes mellitus. Overall, 40 per cent (82) of the individuals had hyperlipidaemia. Whilst the prevalence of hypertriglyceridaemia and combined hyperlipidaemia was greater in patients with insulin-dependent diabetes mellitus than non-diabetics, this was not the case for hypercholesterolaemia. Hyperlipidaemia was present in older patients, and the daily insulin dose and levels of HbA1 were highest in those with combined hyperlipidaemia. In addition normolipidaemic subjects had the lowest levels of serum creatinine. Triglyceride levels were predicted (in order of importance) by insulin dose, age at diagnosis, HbA1 and body mass index, whilst cholesterol levels were predicted by the age at the time of study, body mass index, urinary protein excretion, and levels of fasting blood glucose and HbA1. Hyperlipidaemia is common in insulin-dependent diabetes mellitus, and may be particularly apparent in older patients and/or those with early renal dysfunction or poor glycaemic control. PMID- 2602539 TI - Mortality in Crohn's disease--a clinical analysis. AB - We have examined the causes of death and the changing pattern of mortality over time among 769 patients with Crohn's disease under long-term review between 1944 and 1984. One hundred and fifty-six patients have died. The cause of death could not be classified in five. The deaths were divided into those related directly to Crohn's disease and unrelated deaths from incidental causes. The cause and age at death among 59 unrelated deaths was similar to that expected in the general population. The common causes of related deaths were sepsis, digestive tract cancer, pulmonary embolus and metabolic disorders. There were 30 deaths after surgery, usually from sepsis after emergency surgical treatment. There have been fewer deaths in recent years and the cause of death has altered. Sepsis and electrolyte imbalance have declined in importance and cancer of the digestive tract is now the most common cause of related death. Occasional death from sepsis occurs in elderly patients. Elective rather than emergency surgical treatment and the routine use of antimicrobial prophylaxis before surgery has probably reduced mortality. With the exception of cancer of the digestive tract the appropriate medical and surgical treatment of patients with Crohn's disease can eliminate excess mortality previously associated with the disorder. PMID- 2602540 TI - Fungal peritonitis complicating peritoneal dialysis: report of 27 cases and review of treatment. AB - The clinical features, treatment and outcome of 27 cases of fungal peritonitis were studied. Twenty-one cases occurred in patients receiving CAPD and six in patients on intermittent peritoneal dialysis. Twenty-five cases were due to Candida spp., one was due to Trichosporon spp. and in one, both Candida and Trichosporon and an unidentified acid-fast bacillus were isolated. Clinical features of fungal peritonitis and bacterial peritonitis were the same. A direct comparison with patients without fungal peritonitis failed to reveal an increased incidence of diabetes mellitus. However, a history of recent bacterial peritonitis and antibiotic treatment was frequently obtained. We found that the combination of oral ketoconazole and intraperitoneal miconazole is successful in treating fungal peritonitis complicating peritoneal dialysis but catheter removal and replacement is often necessary. Analysis of the relationship between clinical outcome and various treatment strategies in cases reported in the literature and in our own showed that an initial trial of antifungal drugs consisting of oral ketoconazole and i.p. 5-fluorocytosine or miconazole is warranted in most cases before contemplating catheter removal. PMID- 2602541 TI - The effects of transsphenoidal surgery on endocrine function and visual fields in patients with functionless pituitary tumours. AB - Twenty-eight patients with functionless pituitary tumours have been treated by transsphenoidal surgery over the last 28 months. Mean age at presentation was 55 years. Tumor size was graded according to the extent of suprasellar extension on CT headscan from above the interclinoid line: four were small, 15 medium and nine large. Before surgery in 25 per cent of patients visual acuity and visual fields were normal. In the immediate postoperative period, 24 per cent of the patients with visual defects before surgery had normal vision, and in 38 per cent of the others it was improved. Six months after surgery, there had been further improvement; 43 per cent had normal vision and 48 per cent showed an overall improvement. In no patient did vision deteriorate following surgery. In the patients who presented with visual symptoms of one year or less, there was no correlation between the length of symptoms and the extent of visual recovery after surgery. Average age of the patients with full visual recovery was 47 +/- 4 years (mean +/- SEM); average age of the patients with only partial visual recovery was 63 +/- 3 years. Prolactin levels before surgery were elevated in 77 per cent of patients and fell significantly after operation, remaining elevated in 28 per cent of patients six months later. Fifty per cent of patients were treated with long-term hormone replacement therapy. Transsphenoidal surgery led to improved vision in the majority of patients, the results being comparable with those obtained with transfrontal surgery. Surgical complications were few, and long-term morbidity low. We suggest that the first-line treatment for patients with functionless pituitary tumours should be transsphenoidal surgery, even when large suprasellar extensions are present. PMID- 2602542 TI - Diaphragm strength in the shrinking lung syndrome of systemic lupus erythematosus. AB - The cause of the reduced lung volume in the 'shrinking lung' syndrome of systemic lupus erythematosus (SLE) was investigated in 12 patients with the condition. Nine patients described persistent episodes of pleuritic chest pain. Narrow section (3 mm) computed tomography of the thorax revealed no interstitial fibrosis or significant pleural disease. Assessment of diaphragmatic function using manoeuvres more reliable than the maximal occluded efforts previously used alone to assess respiratory muscle strength, showed that diaphragm strength was unequivocally normal in nine of 12 patients. In three, maximum transdiaphragmatic pressure was moderately reduced, but phrenic nerve stimulation demonstrated that this was due to incomplete activation of the diaphragm during a maximal voluntary effort, rather than to a primary abnormality of the diaphragm. Results of maximum lung recoil pressures and dynamic compliance, and analysis of the 12-s maximum voluntary ventilation, suggested a restriction in chest-wall expansion, although it was not possible to identify the underlying cause of this on the basis of our results. We conclude that the 'shrinking lung' syndrome of SLE is not explained by a primary abnormality of the diaphragm. PMID- 2602543 TI - Prognostic importance of admission plasma glucose in diabetic and non-diabetic patients with acute myocardial infarction. AB - We assessed the relationship of plasma glucose concentrations measured on admission to mortality during the acute phase of myocardial infarction in 143 diabetic patients and 277 patients without a previous history of diabetes. Mortality in hospital in patients not known to have diabetes increased significantly from 4 per cent in patients with admission plasma glucose below 8 mmol/l to 35 per cent in patients with admission plasma glucose above 11 mmol/l. In diabetic patients the mortality increased with increasing admission plasma glucose but the difference was not significant. In patients with diabetes mean admission plasma glucose levels of the survivors and those who died were similar, whilst in the non-diabetic group the mean plasma glucose levels of the patients who did not survive were significantly higher than those of the survivors. Stepwise logistic regression analyses identified admission plasma glucose level as an important predictor of mortality in the non-diabetic group but not in the diabetic patients. Plasma glucose level on admission is an important prognostic indicator in non-diabetic patients, in that hyperglycaemia is associated with a higher mortality. In diabetic patients a clear relationship between admission plasma glucose and mortality was not demonstrated. PMID- 2602544 TI - Variceal bleeding is associated with reduced risk of severe cholestasis in primary biliary cirrhosis. AB - To test the hypothesis that, in primary biliary cirrhosis, bleeding from oesophageal varices implies a reduced risk that a patient will subsequently develop severe cholestasis, the case records of 76 patients with this condition who had died were examined. Fifty-nine patients (78 per cent) had died solely or largely as a consequence of liver disease. Their median survival from the onset of symptoms was 72 months. Most died from either hepatic failure with marked jaundice, infected ascites or variceal bleeding. Fifteen patients had a plasma bilirubin less than 100 mumol/l at the time of death. Twenty-eight patients had had variceal bleeding. Compared with the remaining 31 who had also died from cirrhosis, the patients who had bled from varices survived longer, were much less likely to die of hepatic failure and to become severely jaundiced but were more likely to develop fatal infected ascites. PMID- 2602545 TI - Pseudoseizures. PMID- 2602546 TI - Gastrointestinal events in patients prescribed non-steroidal anti-inflammatory drugs: a controlled study using record linkage in Tayside. AB - The relationship between non-steroidal anti-inflammatory drugs (NSAIDs) and gastrointestinal events has been examined in Tayside by record linkage. From March to October 1983, 57 715 prescriptions for five NSAIDs (ibuprofen, indomethacin, naproxen, Osmosin and piroxicam) were issued to 25 959 patients. Their inpatient morbidity from 1 January 1983 to 31 December 1985 was compared to that of an equal number of control subjects matched for age, sex and general practitioner. Analysis revealed that NSAID takers were more likely to develop disease of the gastrointestinal system (ICD 520-579) and symptoms involving the gastrointestinal system (ICD 787). For females the relative risk was 1.67 and for males 1.28. The difference between NSAID takers and controls increased with age above 60 years and was more pronounced over 70 years. Perforation and haemorrhage of peptic ulcer and gastrointestinal haemorrhage was also higher among NSAID takers after prescription: this difference was dependent upon age but not related to sex. The morbidity of the two groups, control and subsequent NSAID takers, was comparable before the NSAID prescriptions were issued and the control rates remained constant throughout the study. PMID- 2602547 TI - Pseudostatus epilepticus. AB - Thirteen patients with pseudostatus (simulated status epilepticus) have been compared to 13 patients with true status epilepticus seen at a regional neurological centre. Pseudostatus was common in patients with pseudoseizures and was often misdiagnosed as status epilepticus. Complications of this misdiagnosis included eight episodes of anticonvulsant-induced respiratory arrest. Patients with pseudostatus commonly had multiple episodes of 'status'. They usually also had a history of other unexplained illness and of deliberate self-poisoning. Management of these patients was difficult and emphasizes the need for specialist expertise for patients with epilepsy and apparent epilepsy. PMID- 2602548 TI - Haematogenous osteomyelitis in the adult: a clinical and epidemiological study. AB - Isolated reports suggest that haematogenous osteomyelitis in the adult may be presenting to the physician with increasing frequency. The disease continues to cause diagnostic difficulties. Results of a retrospective study of 26 cases over an eight-year period support previous suggestions that a second peak in incidence occurs in the elderly; they are consistent with an increasing incidence although the small numbers make firm conclusions on incidence impossible. The time from onset of symptoms to presentation is often prolonged and diagnostic delay may occur. Those clinical and laboratory features most useful in diagnosis are discussed. PMID- 2602549 TI - The radiography, haematology and biochemistry of pulmonary tuberculosis in the aged. AB - Ninety-three elderly patients with pulmonary tuberculosis were surveyed prospectively to determine the extent and severity of radiological, haematological and biochemical abnormalities. Radiological features of inflammatory changes were present in all patients; 7 per cent of these were purely apical, 48 per cent were in mid and basal zones and in 46 per cent there was a mixed picture. Cavities were seen in 33 per cent of radiographs; half of these occurred in the apical and half in the mid and basal zones. A pleural reaction was present in 46 per cent of cases. Hilar gland enlargement was not seen. Thus radiographs 'atypical' for pulmonary tuberculosis were usual with the major changes being basal and peripheral. Haematological abnormalities were normochromic normocytic anaemia (66 per cent), neutrophilia (69 per cent), thrombocytosis (33 per cent), rapid erythrocyte sedimentation rate (90 per cent), and lymphocytopenia and monocytosis in 22 and 28 per cent respectively. Biochemical abnormalities were hyponatraemia (60 per cent), hypokalaemia (42 per cent), hypoalbuminaemia (83 per cent), and (before treatment) elevation of bilirubin (20 per cent), alkaline phosphatase (62 per cent), aspartic transaminase (77 per cent) and lactic dehydrogenase (74 per cent). The abnormal liver function tests may reflect unsuspected extrapulmonary disease. Radiologically mild opacification occurring frequently in the lower zones and associated with a pleural reaction in half of cases is compatible with tuberculosis. The unexplained presence of any of these haematological and biochemical abnormalities should raise suspicion of the disease. PMID- 2602550 TI - Primary glomerulonephritis and pregnancy. AB - Three hundred and ninety-five pregnancies undertaken by 238 women with primary glomerulonephritis between 1962 and 1987 were analysed to record fetal and maternal outcome and identify risk factors for a poor outcome. Of 398 fetuses, 26 per cent were lost (including therapeutic abortions), 24 per cent surviving infants were premature (less than or equal to 36 weeks gestation) and 51 per cent were term. Excluding therapeutic abortions, 20 per cent of fetuses were lost, 15 per cent after 20 weeks gestation. Fifteen per cent of 237 fetuses whose birth weight was recorded were small for gestational age: Deterioration in maternal renal function was seen in 15 per cent of pregnancies and in 5 per cent of women failed to resolve post partum. Only four women had impaired renal function recorded in the first-trimester and two of these were known to have renal impairment before pregnancy. Hypertension was recorded in 52 per cent of pregnancies, developed early (less than or equal to 32 weeks gestation) in 26 per cent and was severe in 18 per cent. Treated hypertension pre-dated 12 per cent of pregnancies and in 7 per cent (included in the overall incidence of hypertension) exacerbation occurred during pregnancy despite continued antihypertensive medication. Forty-four women (18 per cent) who developed de novo hypertension in pregnancy had permanent hypertension postpartum. Increased proteinuria was recorded in 59 per cent of pregnancies and was irreversible in 15 per cent of women. Comparison of pregnancies which occurred before or after renal biopsy revealed a significantly higher fetal loss rate after 20 weeks gestation in those pregnancies undertaken before the diagnosis of renal disease, and a significantly higher incidence of hypertension and increased proteinuria. Impaired renal function, early or severe hypertension or nephrotic range proteinuria was significantly associated with increased fetal loss, prematurity and fewer full term infants. There was no significant difference in fetal outcome or maternal complications in pregnancy in patients with treated hypertension before pregnancy and those who were normotensive in the first-trimester. The highest incidence of fetal and maternal complications occurred in patients with primary focal and segmental hyalinosis and sclerosis and the lowest in non-IgA diffuse mesangial proliferative glomerulonephritis. The presence of severe vessel lesions on renal biopsy was associated with a significantly higher total fetal loss and fetal loss after 20 weeks gestation. PMID- 2602551 TI - Renal replacement therapy in the elderly. PMID- 2602552 TI - Cerebral nocardiosis in immunosuppressed patients: five cases. AB - Five cases of 'primary' cerebral nocardiosis are described. All occurred in patients already affected by factors carrying a poor prognosis for nocardial infections. These included primary immune dysfunction, immunosuppressive drug therapy including high-dose prednisolone and the presence of cerebral nocardial abscesses. Three of the five patients died, but only two had evidence of continued nocardial infection at necropsy. This compares with mortality of 90 per cent reported in other studies. Therefore aggressive surgical and antibiotic treatment of cerebral nocardial abscesses may reduce the mortality rate in the immunocompromised to the rate seen in immunocompetent patients. We suggest that investigations of non-specific pulmonary symptoms in the immunocompromised should include a search for nocardial colonization as this is indicative of infection. Diagnosis of nocardial infection at the pulmonary stage rather than when central nervous system abscesses are present would lead to an improvement in prognosis. PMID- 2602553 TI - Adult salicylate poisoning: deaths and outcome in patients with high plasma salicylate concentrations. AB - The clinical features, plasma salicylate concentrations, acid-base abnormalities and other biochemical findings are presented for 97 patients who either died from acute salicylate overdosage or survived maximum recorded plasma salicylate concentrations of 700 mg/l or greater. These patients comprised 4 per cent of 2204 cases of salicylate poisoning admitted during the period 1975 to 1985 inclusive. Seven patients died (overall mortality 0.3 per cent); they were significantly older than the survivors, the mortality being as high as 33 per cent in patients over the age of 70 years. Delayed presentation, coma, hyperpyrexia, pulmonary oedema and acidaemia were more common in the fatal cases. Failure to hyperventilate appropriately may contribute to the development of acidaemia. The prognosis of acute salicylate poisoning cannot be determined from the plasma concentration of the drug alone. Clinical features, particularly impaired consciousness, and the arterial hydrogen ion concentration must be taken into consideration. Haemodialysis is the treatment of choice for severe salicylate intoxication and should be used more liberally than it is at present. PMID- 2602554 TI - Pharyngeal size and shape during wakefulness and sleep in patients with obstructive sleep apnoea. AB - Computed tomography has been used to study the pharyngeal airway during tidal breathing in wakefulness and during obstructive apnoeas in Non-REM sleep in patients with obstructive sleep apnoea. In supine subjects, contiguous transverse 10 mm sections were taken perpendicular to the posterior pharyngeal wall with a 2.1 s scan time. Studies during wakefulness showed that the narrowest section of the pharyngeal airspace was in the region posterior to the soft palate and that the minimal airway cross-sectional areas were significantly reduced in the group of patients with obstructive sleep apnoea compared to the group of control subjects without obstructive sleep apnoea. The studies during sleep showed that in all patients, the airspace posterior to the soft palate was a site of obstructive apnoeas. The length of the obstructed segment varied between patients, extending below the level of the soft palate in half the patient group. Airway narrowing and obstruction was due to posterior displacement of the soft palate and the tongue in the majority of patients, although lateral displacement of the pharyngeal walls was also observed. No occlusion was observed in the laryngopharynx although there was narrowing of oro- and laryngopharyngeal apertures below the site of obstruction during obstructive apnoeas. The size of the oropharyngeal airspace during wakefulness did not predict the presence of airway occlusion below the level of the soft palate when asleep. The variability between patients in the site(s) of upper airway obstruction during obstructive apnoeas have important implications for the choice of appropriate treatment in patients with obstructive sleep apnoea. PMID- 2602555 TI - Autonomic neuropathy and chronic liver disease. AB - Autonomic neuropathy has been reported in association with alcoholic cirrhosis but there is no information on its occurrence in non-alcoholic liver disease. We have examined autonomic function in 64 patients with biopsy-proven liver disease (22 with alcoholic liver disease and 42 with non-alcoholic liver disease) together with 29 age-matched controls. Forty-five per cent of patients with alcoholic liver disease and 43 per cent with non-alcoholic liver disease showed evidence of parasympathetic damage; 11 per cent of patients with alcoholic liver disease and 12 per cent with non-alcoholic liver disease had sympathetic damage. Forty-five per cent of patients with alcoholic liver disease and 22 per cent with non-alcoholic liver disease had peripheral neuropathy on clinical examination. Sixty-eight per cent of those with peripheral neuropathy also had autonomic neuropathy. This study confirms that autonomic neuropathy is common in alcoholic patients but the fact that it is found with comparable frequency in non-alcoholic liver disease suggests that the neurological defect may be secondary to the disturbed liver function. The implications of these observations with regard to prognosis of chronic liver disease are discussed. PMID- 2602556 TI - Referral of elderly patients with end-stage renal failure for renal replacement therapy. AB - An increasing number of patients with end-stage renal failure is being treated in the United Kingdom and in 1987 approximately 50 new patients per million started renal replacement therapy. Nevertheless comparatively fewer patients are treated in this country than in some other European countries and in North America. During the 3 years 1985 to 1988, 95 patients from West Glamorgan started chronic renal replacement therapy (87 patients/million population/year). Of these, 16 were aged 75 years or over on starting treatment. In addition two others attained the age of 75 years during the study period. The proportion of elderly new patients is increasing and in the year 1987 to 1988, 59 per cent were older than 65 years and 32 per cent were older than 75 years. Throughout the United Kingdom many elderly patients are being denied treatment, due partly to under-referral. PMID- 2602557 TI - [Three-dimensional structure of crossbridges]. PMID- 2602558 TI - [Conformation changes in crossbridges during contraction and a possible contraction mechanism]. PMID- 2602559 TI - [Approach to mechanism of muscle contraction by molecular micromanipulation]. PMID- 2602560 TI - The effect of PAF in the cochlea of guinea pigs. AB - The influence of 10(-10) and 10(-9) M PAF/animal given into the jugular vein over 30 sec on inner ear potentials, i.e. endolymphatic potential (EP), summating potential (SP) and cochlear microphonics (CM) was investigated. The EP showed the most pronounced changes. When infusing a specific PAF receptor antagonist, ginkgolide B, or the TXA2 receptor antagonist, sulotraban, before the the infusion of PAF, the changes in cochlear potentials could be completely prevented. A second TXA2 receptor antagonist, daltroban, did not effectively prevent PAF actions. It is hypothesized that these PAF effects are due to an interference with ion transport in the non-sensory structures of the inner ear. PMID- 2602561 TI - Effect of indomethacin, cycloheximide, and aminoglutethimide on ovarian steroid and prostanoid levels during ovulation in the gonadotropin-primed immature rat. AB - It has become popular to use the gonadotropin-primed immature rat to study ovulation. The ovarian content of progesterone, estradiol, PGE2, PGF2 alpha, and 6-keto-PGF1 alpha during the ovulatory process was determined in this model. Also, the effect of three anti-ovulatory agents on the ovarian levels of the above substances was determined. At 23 days of age, Wistar rats were primed with pregnant mares serum gonadotropin (PMSG) sc, and two days later the ovulatory process was initiated with human chorionic gonadotropin (hCG) sc. The ovarian follicles began rupturing 12 h later. Ovaries were assayed for the two steroids and prostanoids at 2-h intervals before and several 4-h intervals after ovulation. The ovarian estradiol level increased slightly between 0 and 2 h after hCG, while the progesterone level increased sharply between 2 and 4 h after hCG- at a time when the estradiol declined markedly. All three prostanoids increased concomitantly with progesterone. When the PG synthesis was blocked by indomethacin treatment at 1 h before hCG, ovarian progesterone levels still increased. In contrast, when steroidogenic activity was inhibited by aminoglutethimide, the ovarian prostanoid levels also decreased. Cycloheximide had little effect on the steroids and prostanoids. It is concluded that ovarian prostanoid synthesis might be influenced by ovarian steroid output. PMID- 2602562 TI - Effects of hyperthermia on fetal and maternal plasma prostaglandin concentrations and uterine activity in sheep. AB - The exposure of pregnant sheep to high ambient temperatures (43 degrees C) for 8 hours, sufficient to significantly elevate maternal and fetal body temperature +2.0 degrees C (p less than 0.001) and +1.9 degrees C (p less than 0.001) respectively, resulted in significant increases in PGE2 plasma concentrations in both the maternal and fetal circulations. Plasma PGF2 alpha concentrations were significantly raised in the fetal circulation but not the maternal during hyperthermia. The increase in prostaglandin concentrations were correlated with the magnitude of the increase in maternal and fetal body temperature. Uterine activity also increased during hyperthermia, probably as a result of the increase in prostaglandin concentrations. We propose that increased synthesis and release of prostaglandins from the uterus and/or placenta is an adaptive response to hyperthermia, and may protect the fetus from the consequences of heat stress. PMID- 2602563 TI - In vivo assessment of precursor induced prostaglandin release within the rat gastric lumen. AB - Gastroprotection associated with the intragastric administration of prostaglandin (PG) precursor fatty acids such as linoleic (LA), gamma-linolenic (GLA), and arachidonic acid (AA) has been reported to be mediated via their conversion to PGs. This report examines the relationship between gastroprotection and the extent/rate of PG-release in rats intragastrically administered PG biosynthetic precursors: LA, AA, dihomo-gamma-linolenic acid (DHGL) or oleic acid (OA, a nonprecursor fatty acid). At various times following intragastric administration of a fatty acid, gastric fluid was collected, extracted, chromatographed, and assayed for PGE1 or PGE2 by specific radioimmunoassay. AA and DHGL dose dependently elevated gastric PGE2 and PGE1 levels, respectively. Maximal PGE elevation, 200-400 ng/stomach, was over 400-fold above basal values, and observed within 5-10 minutes of administration. Conversely, OA and LA elicited only a minor (2-10 fold) stimulation of PGE release. In contrast to effects on PG release, all four fatty acids protected the gastric mucosa against macroscopic damage induced by ethanol. The apparent rank order of potency was AA greater than DHGL = LA greater than OA (the difference in potency between DHGL or LA and OA was not significant). Since LA and OA (a nonprecursor) only marginally elevated lumenal PGs relative to DHGL or AA, yet were equally efficacious in the gastroprotection assay, it is likely that other fatty acid-related mechanisms play an important role in protecting the stomach against ethanol-induced injury. PMID- 2602564 TI - The effect of hypoxia on rat splanchnic prostanoid output. AB - The effect of hypoxia on isolated perfused rat mesenteric basal venous prostanoid output was studied. Male rat splanchnic vasculature was removed without (SV) or with its end organ (SV + SI) and perfused with Krebs' buffer with a pO2 of 460 or 60 mm torr. Basal splanchnic venous effluent was assayed for 6-keto-PGF1 alpha, TxB2 and PGE by radioimmunoassay at 30, 60, 120 and 180 min of perfusion. Basal output of SV 6-keto-PGF1 alpha was five and ten fold higher than for PGE and TxB2 respectively and comprised 36% or greater of SV + SI 6-keto-PGF1 alpha output. SV PGE and TxB2 output comprised less than 19 and 12% respectively of SV + SI output. Hypoxia decreased SV + SI PG output, 6-keto-PGF1 alpha being most affected. Hypoxia did not alter SV 6-keto-PGF1 alpha output indicating the SI as the anatomic location most influenced by hypoxia. The relative amounts of distribution of PGE or TxB2 output were not altered by hypoxia. These data suggest that there are two distinct areas of splanchnic prostanoid output, the SV and the SI. Decreased 6-keto-PGF1 alpha output might alter splanchnic blood flow at two levels, the splanchnic vasculature, and/or within the bowel wall. PMID- 2602565 TI - Eating disorders: diagnostic and treatment issues--II. PMID- 2602566 TI - A patient's view of anorexia and bulimia. PMID- 2602567 TI - Reversible EKG changes in anorexia nervosa. PMID- 2602568 TI - Mitral valve prolapse and anxiety disorders in patients with anorexia nervosa. AB - Much has been written about the occurrence of mitral valve prolapse among eating disordered patients. Despite this literature, a causal relationship between the two conditions has yet to be established. The present study evaluated 500 patients with eating disorders and demonstrated an association between a low median ideal body weight and the frequency of mitral valve prolapse (P less than 0.001). The physical signs and symptoms of mitral valve prolapse disappeared in eating disordered patients with the return of normal weight (P less than 0.001). Contrary to prior reports, there was no association between mitral valve prolapse and the occurrence of diagnosable panic or anxiety disorders. The results of this study suggest that the symptoms of anxiety and panic associated with mitral valve prolapse in eating disordered individuals may be due to physiologic change in cardiac status related to weight rather than central nervous system changes associated with classic anxiety disorders. PMID- 2602569 TI - Covert drug abuse in patients with eating disorders. PMID- 2602570 TI - Sexual abuse in patients with eating disorders. AB - The incidence of sexual abuse in eating disorder patients appears significant. Fifty percent of both our anorectic and bulimic patients reported a history of sexual abuse while only 28% of a non-anorexic, non-bulimic control population reported similar problems (p less than 0.01). Several patterns of behavior seemed related to previous sexual assault. In one, the eating disorder was used to change the body image of the patient and therefore to provide a defense to future abuse. Other behaviors which occurred more specifically in bulimic women dealt with a projection of repressed anger toward male authority figures. Forty six percent of the bulimic women seen in our study exhibited some promiscuous behavior, using sex either as a gauge of their own self worth or as a means of punishing men. It is essential that sexual issues be addressed early in the treatment of patients with eating disorders. Disclosure is often difficult particularly in outpatient situations where the patient lives at home with her family. It usually does not occur in such cases until the later stages of therapy, or until the patient is hospitalized. Rape is the exception since our data suggests that it is usually revealed early in the course of treatment (p less than 0.001). Once disclosure occurs, a dramatic change is usually seen in the patient and treatment becomes more effective. As the patient deals with the issues of sexual abuse, they no longer need to deny their sexuality or punish themselves or others. Issues of guilt, depression, repressed anger, low self esteem, social isolation and inadequacy are important and need to be addressed during the course of therapy with sexually abused patients. PMID- 2602571 TI - Multiple family group treatment for eating disorders: a short term program. AB - This paper describes a six session multiple family group therapy program for patients and families dealing with anorexia nervosa and bulimia. The program was developed during the course of treating five such groups in our clinic and was adjunctive to other forms of therapy. The groups were highly structured and combined education, homework, psychodynamically informed group discussions and skills training. The aim of encouraging families to develop a therapeutic environment was made explicit. Responses from patients and families was extremely positive, but most felt the program was too short for their needs. PMID- 2602572 TI - The role of therapeutic recreation with eating disorder patients. PMID- 2602573 TI - Instrument development: always unfinished. PMID- 2602574 TI - Black and Latina womens' AIDS related knowledge, attitudes, and practices. AB - As part of a larger study designed to provide an AIDS education and prevention program for low-income black and Latina women in Los Angeles County, a pilot study of black (n = 51) and Latina (n = 56) womens' AIDS related knowledge, attitudes and practices was conducted to gather baseline data and to test an instrument that would measure these variables. The factors underlying the instrument were identified and reliability coefficients were determined. The need for changes in the format and administration of the instrument was identified due to nonresponse to some items. There were sociodemographic differences between the two groups of women as well as differences in knowledge and attitudes. In general, black women had more knowledge of AIDS than Latina women and more positive attitudes. Practices did not differ. Both groups denied drug use and multiple sexual partners. PMID- 2602575 TI - Quality of life of adults with chronic illness: a psychometric study. AB - Reliability and validity of the Flanagan Quality of Life Scale (QOLS) were tested in four chronic illness groups. Open-ended questions and four instruments, the QOLS, Duke-UNC Health Profile (DUHP), Life Satisfaction Index (LSI-Z), and either the Arthritis Impact Measurement Scales (AIMS) or the Ostomy Adjustment Scale (OAS) were administered by telephone interview and mailed questionnaires to 227 adults three times over 6 weeks. Subjects generated verbal responses that substantiated the content validity of the QOLS. Stability reliability estimates for all instruments ranged from .53 to .90. Cronbach's alpha coefficients averaged .87 for the QOLS. Appropriate validity coefficients indicated both convergent and discriminant construct validity. PMID- 2602576 TI - Role integration and health among female clerical workers. AB - The effects of role identity (occupancy and involvement), sex-role orientation, and role integration on perceived health status and psychological symptoms of women in multiple roles were examined. The sample was comprised of 87 female clerical workers who were mothers with one or more children living at home. The mean age was 37; 47% were married; 44% were black, 24% Caucasian, 15% Asian, and 17% Hispanic. Hierarchical multiple regression analyses were used to determine the significant predictors of perceived health status and psychological symptoms. Role involvement and role integration accounted for 24% of the variance in perceived health. Income and role integration accounted for 29% of the variance in psychological symptoms. PMID- 2602577 TI - Activation--a predictor of need fulfillment in couples. AB - Circadian periodicities in activation were studied in relation to married partners' interactional-emotional need fulfillment. Activation was defined as the phenomenological awareness of general bodily energy state or readiness to respond. It was hypothesized that differences in activation would be related to dissatisfaction with need fulfillment. Activation was measured at four designated times of day by alternate forms of the Activation Checklist (Thayer, 1967) and need fulfillment by parallel forms of the Partner Relationship Inventory (Hoskins, 1988). Five couples completed data series that ranged between 27 and 29 days, providing 67 to 106 pairs of data. Cosine curves were fitted to the data for each subject to test for significant circadian periodicities in each variable. A desynchrony score in activation was calculated for the couple at each measurement time and correlated with the interactional-emotional need scores. The data supported the hypothesis for three subjects. Theoretical interpretations and methodological issues are presented. PMID- 2602578 TI - Identifying critical defining characteristics of nursing diagnoses using magnitude estimation scaling. AB - The question addressed in this study was: Can the critical defining characteristics (CDCs) of nursing diagnoses be determined by magnitude estimation scaling (MES)? MES was used by having 32 nurse subjects numerically estimate the magnitude of each characteristic of anxiety and of sleep pattern disturbance on each of three concept dimensions: importance, frequency, and competency. Geometric means of the stimuli for each of the concept dimensions were computed and correlated with each other. Strong correlations between the characteristics and the concept dimensions were obtained. It was concluded that MES is a useful technique for identifying the CDCs and operational definitions of nursing diagnoses. PMID- 2602579 TI - Neonatal measures of attention and early cognitive status. AB - Measures of infant attention may be more indicative of cognitive status than scores from standardized developmental tests. The purpose of this study of 56 full-term infants was to determine whether measures of attention taken from the Brazelton Neonatal Behavioral Assessment Scales (NBAS) at 2 days and the Bayley Infant Behavior Record (IBR) at 2 months would be internally consistent and would be related to developmental status at 2 months. Attention measures were internally consistent. The IBR measure was significantly related to 2-month developmental status; the NBAS measure was not. Results support attention as an important focus for nursing assessment of development. PMID- 2602580 TI - Gender differences in anger expression: health implications. AB - Anger expression modes were examined in a diverse sample of mid-life men and women (N = 139) participating in the third phase of a longitudinal study of health that began in 1982 at the World's Fair and a metropolitan general hospital in Tennessee. Contrary to previous studies, men and women did not differ in the likelihood of suppressing their anger (anger-in), nor were there gender differences in anger-out. However, t tests revealed significant differences between men and women in the likelihood of discussing anger and expressing anger via physical symptoms (women higher on both). The only mode of anger expression related to poorer health status was expression of anger via physical symptoms; anger-in, anger-out, and anger-discuss modes were unrelated. Correlates of anger symptoms for both men and women included lower levels of education and optimism, poorer health habits, and external locus of control beliefs. Several correlations were found to be gender-specific; e.g., women who exhibited more anger symptomatology were not suppressors of their anger, but directed it outward, taking it out on others and blaming others. Implications were discussed. PMID- 2602581 TI - Trade implications of international differences in toxicological regulations. PMID- 2602582 TI - Nonclinical pharmacologic and toxicologic considerations for evaluating biologic products. AB - Prior to a Phase 1 clinical study, products are studied preclinically to establish evidence of pharmacologic activity, gain an understanding of the mechanism of action, evaluate the potential human risk, and establish a clinical study dose range. Although it is possible to follow this generic itinerary for the development of biologic products, it is difficult to develop generic protocols that will suffice for addressing these preclinical concerns for every biological product. Peptide hormones, cytokines, growth factors, vaccines, allergenics, plasma proteins, enzymes, toxins, monoclonal antibodies, and other heterologous antisera are unique in their physiological interactions, and therefore the toxicologic concerns and suggested studies are tailored to the uniqueness of the compound. This paper represents an attempt to share the thought processes that have been used at the Food and Drug Administration (FDA) to address the nonclinical pharmacology and toxicology study concerns. This presentation of considerations is based on an analysis of what has been done in recent years as a basis for initiating Phase 1 studies (first administration of drugs to humans) and progressing to Phase 2/3 studies (evaluation of optimal dose, effectiveness, and safety in humans), while I was Assistant Director (Pharmacology/Toxicology) of the Office of Biologics and since, as Assistant Director (Pharmacology/Toxicology) of the Office of Drug Evaluation II and a consultant to the Center for Biologics Evaluation and Research. PMID- 2602583 TI - Nursing research: ours is to wonder why. PMID- 2602584 TI - Bedside manners. Advice on how to deal with difficult patients. PMID- 2602586 TI - The importance of teamwork. PMID- 2602587 TI - Research and practice: you can't have one without the other. PMID- 2602585 TI - Legal brief. What sexual harassment is and isn't. PMID- 2602588 TI - As a profession we are coming of age. PMID- 2602589 TI - [Breast reconstruction after mastectomy. Critical analysis of 240 cases]. AB - A retrospective study on 240 cases of breast reconstruction was undertaken in order to make a critical analysis of the results of different techniques as silicone prosthesis, tissue expanders, and the myocutaneous flaps of latissimus dorsi and rectus abdominis. The authors discuss the indications, advantages, inconveniences and complications of each technique and point out the particular indications for each one, depending on the type of mastectomy performed and the quality of the remaining tissues. Good results can be obtained using prosthesis, or flaps, but the indications must be very criterious, as the number of complications may be high, and many operations might be needed to achieve a satisfactory result. PMID- 2602590 TI - [Hemorrhagic angiodysplasia of the upper digestive tract: endoscopic diagnosis and treatment]. AB - Angiodysplasia of the gastrointestinal (GI) tract is considered probably the most common cause of the occult bleeding. This paper analyses retrospectively 8 patients with angiodysplasia from upper GI tract. Two of them had Rendu-Osler Weber syndrome. The main symptom was upper GI bleeding and 5 patients had acute melena and 3 chronic-intermittent bleeding. The diagnosis of angiodysplasia was confirmed by endoscopy. All patients but one underwent endoscopic treatment by injections of sclerosant and vasoconstrictor agents. One patient had hemigastrectomy and died in the post-operative. In the follow-up of 10 to 41 months, 2 patients died, one with bronchial carcinoma and the other due to cardiopulmonary failure. There was no bleeding recurrence in 5 patients. The endoscopic therapy should be the first choice if it is feasible, considering its efficacy as well as the low cost and safety. PMID- 2602591 TI - [Results of early thoracotomy in the treatment of non-calcified solitary pulmonary nodules. Analysis of 19 cases]. AB - We reviewed 19 patients who had undergone thoracotomy and resection of a noncalcified solitary pulmonary nodule over the past 7 years, to see if a policy of early thoracotomy was therapeutically valid. The average age of patients was 50 (range 10 to 73 years), 6 females and 13 males. All of them asymptomatic. In this study, there were 9 (47.3%) of primary bronchogenic carcinoma, the incidence was 54.5% in patients above 50 years. There were no postoperative deaths and 3 serious postoperative complications (15.7%). Post operatory followed up by all patients ranged from one to seven years. The patients with benign lesions are all well. 9 of the cases had primary lung cancer, 2 died, 3 1/2 years and 5 years after surgery. We conclude that pre-operative differential diagnostic procedure between benign and malign nodules may not always be decisive, and that an early thoracotomy in indicated every case, since the incidence of malign tumors is frequent. Very small primary lung cancers detected and treated early do not have the same poor prognosis as larger primary cancers. PMID- 2602592 TI - [Hospital infection at a private hospital in Ribeirao Preto, Sao Paulo, Brazil]. AB - The aim of this work is to prospectively evaluate the incidence of infection, from June 1986 to June 1987, in 640 patients submitted to surgical treatment at the Sao Francisco Hospital, in Ribeirao Preto, Sao Paulo, Brazil. The overall incidence of infection was 10.31%. The incidence of wound abscess was 6.25%, and urinary infection 5.75%. In the surgical procedures considered as clean, the infection rate was 8.62%, in the clean-contaminated 14.81%, in the contaminated 8.33%, and in the dirty 16.94%. The antimicrobian drugs contributed to increase the infection rate. The hospital infection rate for the patients at infirmaries was 10.88%, and for the patients at private rooms 4.92%. The mortality rate due to hospital infection was 12.12%. The authors stress that a constant attention with the hospital infection is needed to verify the infection rate to be able to make a control program of the asepsis, antisepsis and sterilization methods, as well as to improve the operative techniques and the patient's management during the pre, per and postoperative period. PMID- 2602593 TI - A prospective study of asthma during pregnancy and the puerperium. AB - Thirty-one asthmatic women recruited in an ante-natal clinic were followed during pregnancy and for six weeks of the puerperium. Subjectively 22 (69%) women considered their asthma to have improved, two were worse and in seven (22%) there was no change. Analysis of peak flow rate, symptoms score and bronchodilator use showed that in ten pregnancies there was improvement in the third trimester and that in 11 there was deterioration in the puerperium. The results suggest that in patients with mild or moderate asthma an improvement is likely to occur during pregnancy, particularly in the last trimester, but that in over one-third there may be a post-natal deterioration. Review of the literature suggests that severe asthmatics are at greater risk of deterioration, particularly late in pregnancy. PMID- 2602594 TI - The repeatability and validity of respiratory resistance measured by the forced oscillation technique. AB - Measurement of forced expiratory volume in one second (FEV1) is commonly used in bronchial challenge testing in laboratory and epidemiological studies but has certain disadvantages. We have therefore studied the repeatability and validity of a derived measurement of respiratory resistance (Ros) obtained with the Siregnost FD5 impedance oscillometer (Siemens). Repeatability was estimated in 25 non-asthmatics and 28 asthmatics and compared with that of PEFR, FEV1 and specific conductance. PEFR and FEV1 were the most repeatable. Repeatability for measurements with the oscillometer as measured by the intraclass correlation coefficient for a single measurement was 0.75 for non-asthmatics, but was less good for asthmatics (intraclass correlation coefficient 0.56). To assess the validity of respiratory resistance measured during a histamine bronchial challenge test a sample of 20 hospital personnel was studied on four occasions, FEV1 and Ros both being measured twice. Ros changed at lower doses of histamine than FEV1, but the intraclass correlation coefficient for repeatability of change only reached 0.6 at an absolute dose of 3.41 mumol histamine. The estimated provocation dose of histamine producing a 35% fall in Ros was 8.70 mumol (95% range for a single measurement +/- 1.11 doubling doses), that producing a 10% fall in FEV1 was 8.32 mumol (95% range +/- 1.04 doubling doses) and a 20% fall in FEV1 11.48 mumol (95% range +/- 1.11 doubling doses). Measurements obtained with the Siregnost FD5 oscillometer are repeatable. The use of Ros during bronchial challenge testing is valid, but shows insufficient advantage over FEV1 to support its use in epidemiological studies. PMID- 2602595 TI - Alpha 1-antitrypsin serum levels in widespread bronchiectasis. AB - This study found significantly higher serum levels of alpha 1-antitrypsin (alpha 1-AT) in 35 patients with widespread bronchiectasis compared with healthy controls. The results are in contradiction with a previous study and four case reports which found an association between alpha 1-AT deficiency and bronchiectasis. However, the validity of the association has been questioned in the literature on the grounds that most of the patients in those reports had other possible aetiologies for their bronchiectasis. We believe the raised level of alpha 1-AT in our patients represents a non-specific acute phase response to bronchial infection. Further studies are needed to clarify whether bronchiectasis, like emphysema, can be a manifestation of alpha 1-AT deficiency. PMID- 2602596 TI - Ethnic variation in respiratory function in young children. AB - The effect of ethnic origin on respiratory function was assessed in 57 young children aged between 4.9 and 8 years. Functional residual capacity (FRC) and peak expiratory flow rate (PEFR) were measured and related to sitting and standing height in Caucasian and Afro-Caribbean children. No significant differences were found between the two groups in PEFR when related to either standing or sitting height. FRC, when related to standing but not sitting height, was greater in Caucasian children (P less than 0.01). Sitting height related to standing height was lower in children of Afro-Caribbean descent (P less than 0.01), suggesting that anthromorphic differences may explain the apparent influence of ethnic origin on respiratory function in young children. PMID- 2602597 TI - Time of exposure as a prognostic factor in avian hypersensitivity pneumonitis. AB - Spirometric values were subsequently evaluated in 22 patients suffering from hypersensitivity pneumonitis caused by avian problems. First spirometric values were abnormal in 18/22 (82%) of patients. A restrictive pattern was observed in 16/22 (72%) of patients and an obstructive pattern in 6/22 (27%). The TLCO was reduced in all cases (12/12). Improvement or normalization of the respiratory function occurred 3.4 +/- 2.4 months after the avian contact had ceased. At the end of the follow-up, parameters were normal in 13/22 (59%) of patients. The restrictive pattern remained unchanged in 7/22 (32%), and the obstructive pattern persisted in 4/22 (18%) of the patients. The TLCO was normal in 6/12 (50%) of patients. Neither age nor treatment with corticosteroids (13 patients) had a significant influence upon the evolution of the lung function. However, total recovery or significant improvement was observed in 12/12 (100%) of patients who had been in contact with birds less than 2 years, in contrast to 6/10 (60%) of patients with more than 2 years of contact (P = 0.002). PMID- 2602598 TI - Kyphoscoliosis as a cause of cardio-respiratory failure--pitfalls of diagnosis. PMID- 2602599 TI - Endobronchial metastases simulating primary carcinoma of the lung. PMID- 2602600 TI - Miliary tuberculosis and the adult respiratory distress syndrome. PMID- 2602601 TI - Aspergillus colonization of pulmonary rheumatoid nodule. PMID- 2602603 TI - Evaluation of a hand-held spirometer, the Respiradyne, for the measurement of forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) (1) PMID- 2602602 TI - Intrathoracic manifestations of disseminated prostatic adenocarcinoma. AB - Four cases of disseminated adenocarcinoma of the prostate illustrating the clinical spectrum of intrathoracic involvement in this disease are presented. In two cases the presenting features of prostatic cancer were with lymphangitis carcinomatosa and an isolated pleural effusion, whereas two other cases developed intrathoracic metastases in the setting of previously known locally advanced prostatic cancer. In one this took the form of hilar and mediastinal lymphadenopathy and in the other that of pulmonary nodules. An immuno cytochemical marker for prostatic specific antigen, a highly sensitive and specific tool for identifying prostatic epithelium, identified the prostate as the primary site of malignancy in the first two cases. Symptomatic and radiological responses were noted in all four cases after bilateral orchidectomy. Pulmonary metastases are common in the advanced stages of prostatic cancer but may also be present at the initial presentation with the disease even when the primary tumour is not clinically apparent. We recommend that (i) immuno cytochemical stains for prostatic specific antigen are applied to all lung, pleural and mediastinal biopsy specimens showing adenocarcinoma in male patients, and (ii) all males with intrathoracic adenocarcinoma have prostatic aspiration cytology performed if the prostatic specific antigen stain is positive. PMID- 2602604 TI - Building sickness syndrome. PMID- 2602605 TI - Is CT scanning essential in the pre-operative assessment of lung cancer? PMID- 2602606 TI - [The Fuenlabrada study: a familial aggregation of ischemic cardiopathy and cardiovascular risk factors]. AB - Familial aggregation of coronary heart disease (CHD) and coronary risk factors (CRF) were evaluated by clinical history in adult relatives of children surveyed for CRF. Population was divided into two groups: Group I included 2,153 children without parental history of CHD. Group II included 266 children of 112 families with parental history of early CHD (before 56 years). In 105 cases the patients were the fathers and in 7 cases the mothers. All the patients were admitted to a coronary care unit. Familial aggregation of CHD was 9.7 times more frequent in paternal families of group II (p less than or equal to 0.0001) than in group I; there was no differences in maternal families. Higher prevalence of hyperlipidaemia, blood pressure hypertension, smoking habits, diabetes and obesity in fathers of group II was observed. Children in group II showed increased levels of C-LDL and decreased levels of C-HDL compared with those of group I. The prevalence of CRF was also significantly higher in children of group II, although in the 33% of the children of group II no CRF was detected. CONCLUSION: a substantial proportion, but not all cases, of familial aggregation of CHD could be explained by known CRF. PMID- 2602607 TI - [Evaluation using serial exercise tests of verapamil alone and combined with isosorbide dinitrate in exertional angina]. AB - The response to verapamil alone and combined with isosorbide dinitrate in a group of 12 patients with severe ischemic heart disease and stable effort angina was assessed by means of serial treadmill testing. The study was randomized, of a square latin design and double-blind. The tested drugs and dosages were 120 mg of verapamil, 120 mg of verapamil plus 20 mg of isosorbide dinitrate and placebo. Patients were serially tested (Bruce protocol) over three consecutive days at 8-9 12 and 16 hours. A significative improvement was observed in several ischemic parameters both with verapamil alone and combined with isosorbide dinitrate, but this improvement was remarkably enhanced with the combination of drugs. The mean exercise time to produce angina improved from 268 +/- 18 sec (basal) to 379 +/- 19 sec (verapamil plus isosorbide dinitrate) and the time for 1 mm ST segment depression from 163 +/- 22 sec (basal) to 257 +/- 19 sec (verapamil plus isosorbide dinitrate) when measured at the last daily test (8 hours after drug administration). It is concluded that both verapamil alone and combined with isosorbide dinitrate at the chosen doses are clinically efficient, significantly improving the ischemic parameters. The combination of verapamil and isosorbide dinitrate resulted in a remarkably better improvement in this group of patients with stable effort angina. PMID- 2602608 TI - [Silent myocardial ischemia during Holter monitoring in patients with diabetes mellitus]. AB - To evaluate the prevalence and characteristics of silent myocardial ischemia in asymptomatic patients with non insulin dependent diabetes mellitus, 50 diabetic patients (24 males, 26 females; mean age +/- SD = 58.3 +/- 6.4 years) with a normal resting electrocardiogram were prospectively studied. The total group underwent 48 hours electrocardiographic Holter monitoring, medical history, physical examination an a test for cardiac autonomic neuropathy. Serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and Hb A1c were determined. An ischemic episode was defined as asymptomatic ST-segment depression greater than or equal to 1 mm, greater than or equal to 1 min. Day-to day variability was studied. Six hundred and forty one episodes with a total duration of 1,014 minutes of ischemia were recorded in 29 patients (58%). The mean number of episodes in 48 hours per patients was 19.2 +/- 21.9 and the mean time of ischemia over this period was 149 +/- 374 minutes. The average heart rate at the onset of the episodes was 95.2 +/- 8.4 beats per minute. Two hundred and ninety two (45.6%) episodes occurred without heart rate changes and in 349 (54.4%) episodes an increase in heart rate was detected at the onset of the episode. An important day-to-day variability in the number of episodes (73.8 +/- 29.5%) and ischemia duration (76.9 +/- 88.8%) was found. Fifteen patients had no ischemic episodes in either the first or second monitoring day. Silent ischemia was related to higher levels of total cholesterol (p less than 0.05), LDL cholesterol (p less than 0.05) and Hb A1c (p less than 0.01) and was associated to diabetes complications: retinopathy (p less than 0.001), peripheral vascular disease (p less than 0.01), polyneuropathy (p less than 0.05), nephropathy (p less than 0.05), and impotence (p less than 0.01). Silent ischemia was not associated to abnormal test for cardiac autonomic neuropathy. CONCLUSIONS: prevalence of silent myocardial ischemia during daily activities in asymptomatic diabetic patients is very high (58%). Both an increase in oxygen demand and a decrease in oxygen supply may be involved in its pathophysiology. In diabetic patients silent ischemia is related to the presence of other risk factors for coronary artery disease and to diabetes complications and shows a marked day-to day variability. PMID- 2602609 TI - [Role of intraoperative echo-Doppler color echocardiography in cardiac surgery. Preliminary study]. AB - Intraoperative echocardiography with Doppler color flow imaging technique can provide the surgeon with an immediate and direct assessment of cardiac anatomy and function. To determine the utility of this recent technique, we have examined 15 patients pre, per, and postoperatively with Doppler color flow imaging. The intraoperative study was performed before and after cardiopulmonary bypass. A sterile transducer was placed directly on the epicardial surface of the heart, and multiple views were recorded. Intraoperative echocardiography with Doppler color flow imaging technique demonstrated excellent correlation with preoperative and postoperative findings, allowing an immediate evaluation of the surgical results. These preliminary results suggest that intraoperative Doppler color flow imaging technique is a valuable adjunct in heart surgery. It is particularly useful in valve repair, and in surgical repair of congenital heart disease. PMID- 2602610 TI - [Use of aspirin in the primary prevention of vascular thrombi. A comparative study with other anti-aggregant drugs]. AB - We have induced the formation of arterial (carotid) and venous (femoral) thrombi in dogs by means of an intima lesion produced by continuous current. The platelets were labeled with 111In oxine. Groups of 7 mongrel dogs received treatment for 7 days prior to the trial: group I, control; group II, 5 mg/kg body weight/day acetylsalicylic acid; group III, 20 mg/kg body weight/day acetylsalicylic acid; group IV, 15 mg/kg body weight/day triflusal + 5 mg/kg body weight/day dipyridamole; group V, 15 mg/kg body weight/day triflusal; and group VI, 5 mg/kg body weight/day acetylsalicylic acid + 5 mg/kg body weight/day dipyridamole. The only effective treatment for arterial thrombosis prevention was that employed in group II (p less than 0.05). Venous thrombosis was prevented in groups II (p less than 0.01), III (p less than 0.01) and VI (p less than 0.01). PMID- 2602611 TI - [Fatal acute myocardial infarct in a 14-year old boy]. AB - The case of a 14 year old male, with no personal or family antecedents of ischemic heart disease, who died owing to an acute myocardial infarct into the few hours of beginning to pain. In the necroscopic study it was observed that the coronary arteries did not show any anatomical alterations or stenosis from their origins, although a microscopic study revealed extensive zones of necrosis. PMID- 2602612 TI - [Pericardial mesothelioma: apropos of a case]. AB - We report a case of primary pericardial malignant mesothelioma in a 53-year old male with no asbestos previous exposure. The first clinical sign was a massive pericardial effusion causing hemodynamic disturbances. CT confirmed the initial ecochardiographic diagnosis. The patient underwent pericardiocentesis which improved his hemodynamic status as well as showed malignant cellularity in the liquid examination. Surgical treatment, including pericardiectomy and tumor resection, together with chemotherapy restored normal hemodynamics, the patient being now asymptomatic. We want to emphasize the rarity of this tumor and its insidious clinical presentation even leading to hemodynamic impairment, as well as the great value of echocardiography and CT in its diagnosis, although, in some cases, thoracotomy has been the only valid diagnostic procedure. PMID- 2602613 TI - [Descriptive and prognostic value of health status perception by a group of patients with chronic respiratory insufficiency using respirators]. AB - Using a self questionnaire we have done a domiciliary study of the perception of health and respiratory function in a population of 537 patients suffering from chronic respiratory disease. We arranged elsewhere the objective biological data of the severity of the disease represented in the computerised dossier on each patient and were able to compare this objective data to the subjective data gathered by the questionnaire. The objective data, in particular the blood gas analysis, appeared to be very weakly linked to the perception that the subjects had of their health and of their physical mobility. A study of the survival at one year showed that functional capacity and psychological approach of subjects were better predictive factors of mortality than the severity of the disease defined according to medical criteria. This study recalls the limits of standard methods of follow up for chronic respiratory failure, and stresses the importance of physical independence in these subjects: this functional indicator seems to have a value which is both descriptive as it is connected, as a whole, to the indicators of the quality of life and also prognostic as it is a better predictive factor for mortality at one year. PMID- 2602614 TI - [Late disseminated tuberculosis. Anatomo-clinical correlations in 40 cases]. AB - Late disseminated tuberculosis has a diversity of clinical presentations and is difficult to diagnose. This disease has a growing importance in industrialised countries and we decided to study forty cases correlating autopsy findings with the clinical date. This diffuse form of miliary tuberculosis occurs long after the primary infection. It is a disease of the elderly (72.5% greater than 65, 32.5% greater than 80). It represented 42.5% of serious tuberculous cases observed at autopsy over the same period. At the top of the list of clinical presentations is fever (57.5%) followed by loss of weight (42.5%) and respiratory symptoms (32.5%). The diagnosis of tuberculosis was only considered in 37.5% of cases (15/40), however the pulmonary radiograph suggested the diagnosis in the majority of cases. In 62.5% of cases (25/40) tuberculous disease was not recognised in the clinic, the presenting symptomatology was attributed in nearly half the cases to neoplastic disease. Autopsy showed that the primary disease was caseous tuberculosis in 25% of cases and in 25% there was a cancer. Our observations underline the diagnostic challenge of late disseminated tuberculosis in clinical practice and also discern the particular clinical characteristics and anatomo-pathological features. PMID- 2602615 TI - [Should a cancer of the bronchi be surgically treated after excision of a cerebral metastasis?]. AB - Between 1964 and 1987 35 patients were operated on for cerebral metastases due to an underlying bronchial carcinoma. In 26 cases (group 1) there was excision of the primary tumour also and in 9 cases combined medical treatment was given with radiotherapy and chemotherapy. The neurological state was improved by the neurosurgical operation in 88% of patients in group 1 and in 66% of patients in group 2. This improvement was maintained in 30% of the patients as long as they survived. 2 patients died following thoracic surgery (7.69%). The median survival was 11 months in group 1 and 9 months in group 2. Three patients in group 1 were living two years after craniotomy whilst. 1 patient in group 2 is still alive four years after the neurosurgical procedure. The heterogeneity of the two groups does not permit a comparative statistical analysis but overall there does not seem to be any difference in duration or quality of life between the two groups. Complementary cerebral radiotherapy did not affect the prognosis. PMID- 2602616 TI - [Hospitalizations for diseases of the respiratory system at public assistance hospitals in Paris in 1985]. AB - This study is an analysis of the reasons for hospitalisation for respiratory diseases in 1985 in the eleven departments of pneumology (SP) and departments of Internal Medicine (SMI) in the public hospitals in Paris. As well as epidemiological data systematically gathered on the discharge of the patients the number of stays for respiratory diseases, the mean duration of stay (DMS), sex, age and place of residence of the patients were studied. 59 diagnostic codes were considered as covering the overall pattern of respiratory pathology (OMS) classification at 3 levels 9th revision). Amongst those 24 were regrouped into 7 pathological groups considered as characteristic of the discipline of pneumology: asthma, chronic airflow obstruction (BPCO), malignant tumours of the respiratory tract, pulmonary embolism, respiratory infections, sarcoidosis and tuberculosis. There were 30,877 inpatient stays for respiratory disease identified, representing 6.6% of all hospitalisations in the medical service of the public hospitals. 41.1% of stays were in SP and 24% in SMI. 78% of the stays in SP were for respiratory diseases against 10-15% in SMI. In SP asthma represented an average of 11% of all hospitalisations for respiratory disease, BPCO was 13%, cancer 35% and pulmonary embolism 4%, sarcoidosis 2%, respiratory infections 8% and tuberculosis 8%; great variation were noted according to the different units which enabled a hospital profile to be identified and which gave the general orientation of a particular service. In SMI this profile was different: there was a smaller percentage of cancer cases and a higher level of infectious disease. The mean stay was shorter in SP than in SMI (10.4 v 13.8 days) for respiratory cases overall and whatever pathology that was studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602617 TI - [Is thoracic actinomycosis underestimated? Reflections on 7 cases]. AB - An analysis of 7 cases of thoracic actinomycoses were recorded over 25 years enabling a better appreciation of the radiological and clinical criteria: a low grade pneumonia with haemoptysis and an alteration in the general physical state, with pseudo-tuberculous radiological images or "pseudo-tumoral" with bronchograms and parietal wall disease. This clinical picture calls for endoscopic biopsies or biopsies under CT scanning for a study combining both histological and bacteriological diagnosis on appropriate culture media, enabling an exploratory thoracotomy to be avoided, the latter the classic method of diagnosis. This approach should reduce the number of pneumonias which are not confirmed bacteriologically which are sensitive to the usual antibiotics and determine better the true frequency of actinomycoses. PMID- 2602618 TI - [Respiratory tuberculosis in Seine-Saint-Denis. Results of treatment]. AB - A study was carried out in 1984-1986 in Seine-Saint-Denis on the clinical management of tuberculous cases. It was possible to observe in routine practice the nature, duration and results of treatment in 336 adult cases suffering for the first time from respiratory tuberculosis. The recommendations of the French Society of Pneumology were taken as a reference. A minority of patients (22%) were treated entirely at home. The others were admitted to hospital then treated at home (33%) or had a stay in a sanatorium (45%). The mean duration of stay in institutions was five months for those patients staying in a sanatorium. The most common therapeutic regime in the initial phase consisted of rifampicin and isoniazid, with additional ethambutol alone (60%) or ethambutol in combination with pyrazinamide (15%). The mean duration of treatment was 10.5 months, without any difference between those regimes consisting of three or four drugs. At the end of the period of treatment 85% of patients were considered to be cured; 16 patients (or 5%) had died and 18 patients (6%) were lost to follow up before the end of treatment. There were 15 patients (or 4%) who showed no significant change between the beginning and the end of the study. PMID- 2602619 TI - [Pheochromocytoma revealed by pulmonary edema]. AB - We report the case of a young patient of 37 presenting with two attacks of pulmonary oedema which revealed an underlying pheochromocytoma. The diagnosis was suggested by the raised level of vanyl-mandelic acid in the urine and the abdominal CT scan. After an adrenalectomy the outcome was satisfactory. Pheochromocytoma should be considered in the differential diagnosis of the acute respiratory distress syndrome in the adult linked to the action of the circulating catecholamines on the pulmonary capillaries. PMID- 2602620 TI - [Phrenic stimulation in C1-C2 tetraplegia. Apropos of a case]. AB - The authors report a case of post traumatic tetraplegia at the C1-C2 level in a young man of 16 with total respiratory paralysis treated with mechanical ventilation and a tracheotomy. Thirty months after the accident, an Avery S 232(1) diaphragmatic pacemaker was surgically implanted by the mediastinal approach. The technique was rapidly successful and enabled satisfactory ventilation and phonation two months after the implantation. The patient is currently treated at home with no signs of diaphragmatic fatigue 20 months after the implantation of the stimulator. PMID- 2602621 TI - [A case of atypical pulmonary sequestration]. PMID- 2602622 TI - [A double radiologic curiosity]. PMID- 2602623 TI - [Diagnosis of a mediastinal opacity]. PMID- 2602624 TI - [Recommendations apropos of contraindications and precautions in the use of bronchial cryotherapy with a flexible catheter]. PMID- 2602625 TI - [Multiple elemental organic components of the broncho-alveolar lavage fluid in normal subjects and in various lung pathologies (excluding silica and asbestos fibers)]. AB - Owing to a technical analysis enabling the detection of mineral elements present in trace amounts in small volumes, an analysis of the liquid obtained in 148 broncho-alveolar lavages could be studied. The elements consistently recovered were as follows: iron, copper, zinc, nickel, lead and titanium. Normal values were established. In the absence of exposure, there was no significant difference distinguishing the different pulmonary diseases studied. In occupational disease, the presence of iron in large quantities, tungsten, nickel and rare earths could be shown objectively, as well as the persistence of gold or iodine after medical absorption. However, this preliminary work does not allow one to establish a formal correlation between the alveolar concentrations obtained and the pulmonary disease observed. PMID- 2602626 TI - [Effects after 3 months of uvulopalatopharyngoplasty in the treatment of obstructive sleep apnea syndromes in adults]. AB - The results at three months of uvulopalatopharyngoplasty (UPPP) have been evaluated in thirty adult patients with an obstructive sleep apnoea syndrome (SAOS). For the group overall the mean apnoea index (IA) decreased from 57 apnoeas per hour and the mean maximal desaturation decreased to 60% post operatively. However in the overall results different individual facts overlap. 20 of the 30 patients, or 67%, have an IA post operatively of less than 50% of the pre-operative value (responders). 14 of these or 47% have a post operative IA of less than 10 apnoeas per hour, a value considered as non pathological. Finally 33% of the patients have no improvement in their post operative IA (non responders). A stricking diminution of nocturnal desaturation and of the disorganisation of sleep was seen in responders to UPPP. No predictive factor for the results of UPPP could be determined. This study shows that UPPP is an effective treatment in a large number of patients having SAOS at the price of minor and transitory complications. PMID- 2602627 TI - [Effect of a single dose of nifedipine on the CO transfer capacity in patients with scleroderma]. AB - The calcium antagonists are currently used in the treatment of Raynaud's syndrome for patients with scleroderma. The effect on the pulmonary vasculature in these patients is little understood. The study reported here is based on 15 patients with scleroderma. In each patient lung volumes, expiratory flow and transfer factor (DLCO) were carried out in a basal state and one hour after the administration of sub lingual nifedipine. Nine patients showed a diminution in the DLCO before taking the product but the mean variation after nifedipine was not significant. Different mechanisms may explain the absence of any effect: irreversible vascular disease or the absence of pulmonary arterial hypertension or hypoxic constriction, the latter conditions were previously associated with the efficacy of nifedipine. Thus it does not seem that nifedipine, in acute tests, has an effect on the pulmonary localisation of scleroderma, at least in the absence of pulmonary arterial hypertension. PMID- 2602628 TI - [Respiratory signs associated with gastro-esophageal reflux. A retrospective study of 132 surgically treated cases in children and adults]. AB - We carried out a retrospective study of 132 cases of respiratory disorders associated with gastro-oesophageal reflux involving 66 children, 42 boys and 24 girls, 4 days to 10 years old with a mean of 22 months. We also studied 66 adults, 37 men and 29 women, 16 to 74 years old. In the infants the mean duration of respiratory disorders was 17 months and a recurrent broncho-pulmonary infection was the principal indication (40 cases). Alimentary symptoms were present in 34 cases. There was evidence of reflux in 60 cases. The suppression of any reflux was obtained surgically in 95% of cases with a disappearance of the respiratory disorders in 78.6% of cases and their improvement in 16.4% of cases with a mean follow up period of 4.3 years. In the adults the mean duration of the respiratory disorders was 9.7 years and asthma was the principal cause (38 cases). Alimentary symptoms were present in 56 cases with evidence of reflux in 64 cases. A suppression of the reflux was achieved surgically in 94% of cases with a disappearance of the respiratory disorders in 36% of cases and their improvement in 28% of cases with a mean follow up period of 4.7 years. The correlation between the disappearance of reflux and the respiratory symptoms and signs in the children should perhaps be tempered by the natural history of the maturation of the inferior oesophageal sphincter. However surgery shortens the danger period in serious situations which are life threatening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602629 TI - [Experimental study of the pleural effects of the pulverization, under thoracoscopic control, of a fibrin glue (Tissucol)]. AB - The instillation of a fibrin sealant (Tissucol) has been proposed in the treatment of recurrent spontaneous pneumothorax. The present work is devoted to an experimental study in the dog of the effects of this substance on the pleural cavity one and two weeks after instillation under thoracoscopic control. Its action is compared to that of placebo (methylene blue). The instillation of a placebo (n = 5) did not alter the ventilatory mechanics or the structure of the pleura. On the other hand Tissucol (n = 6) led to a fall in the thoraco-pulmonary compliance (-14%), corresponding to that of the vital capacity (-10%). In these animals, no pleural symphysis was noted, but the histological analysis gave evidence of changes in the layers of the parietal and visceral pleura: an inflammatory mononuclear reaction (71% of cases) and/or polymorphonuclear (54%), recent fibrosis (67%) and more rarely a mesothelial hyperplasia (21%). The maintenance of the integrity of the mesothelial cellular layer would explain the absence of pleural symphysis after instillation of Tissucol. These results as well as those recently obtained in the human situation prompt us to advise other methods of pleural symphysis which have been tried and tested, such as talcage or surgery. PMID- 2602630 TI - [Pulmonary and muscular localization of Wegener's granulomatosis. Apropos of a case]. AB - The authors report their observations on a patient presenting with Wegener's granulomatosis with initially isolated pulmonary involvement. Following treatment with a combination of steroid therapy and immunosuppressives muscular involvement developed with specific histological changes. The disease was only controlled by substituting at the same dose prednisone for the methylsulphobenzoate of prednisolone which was prescribed initially; this suggests in equivalent doses the superiority of one product over the other was achieved by a different pharmacodynamic behaviour. PMID- 2602631 TI - [Protein-poor pleurisy and mesothelioma. Apropos of 2 cases]. AB - We report two cases of protein poor pleural effusions secondary to malignant mesothelioma which were proven histologically. In the absence of any extra pulmonary cause, in particular cardiac, the associated investigations carried out led to the exclusion of either a chylothorax or a mechanical effusion due to atelectasis. Pulmonary venous obstruction by the mesothelial masses which had developed on the mediastinal pleura were shown in the two cases. The high pressure in the pulmonary capillaries which resulted could be the origin of the low level of protein observed in the pleural fluid. PMID- 2602632 TI - [Cardiotoxicity of 5 fluoro-uracil. Apropos of a case]. AB - The cardiotoxicity of 5 fluoro-uracil is currently recognised. We report here a new case in which an effort test and a Methergin test were carried out in the hours following the episode and at a later date. With normal coronary arteriography the evidence is in favour of coronary artery spasm which is the usual mechanism for this type of toxicity. PMID- 2602633 TI - [Pneumomediastinum in dermatopolymyositis]. AB - The authors report the occurrence of a pneumomediastinum occurring in a young female aged 25 who had already been under treatment for 3 years for dermatomyositis and who had a pulmonary involvement with fibrosis. This association did not seem fortuitous. The pneumomediastinum would be due to a cystic degeneration of the fibrosis producing "pseudoblebs". PMID- 2602634 TI - [A gastric tumor and pulmonary nodule]. PMID- 2602635 TI - [Hydropneumothorax of an unusual cause]. PMID- 2602636 TI - [Pseudo-tumor of the upper mediastinum]. PMID- 2602637 TI - [Prognostic factors in multiple myeloma. Selection using multivariate analysis]. AB - In order to assess the prognostic value of 15 different prognostic variables for multiple myeloma and to select the variables with the best prognostic significance, the multivariate analysis according to Cox's proportional hazard regression model was employed for a group of 80 patients followed from first diagnosis to their demise. The significant prognostic variables were bone marrow plasma cell percentage, degree of lytic bone lesions, Bence-Jones proteinuria, and haemoglobinaemia. A scoring clinical staging system was also developed, assigning the score of 1 to each of the following features: bone marrow plasma cells more than 30%, lytic bone lesions of 2-3 degrees, presence of Bence-Jones proteinuria, and haemoglobinaemia less than 110 g/l. Therefore, the score for each patient ranges from 0 to 4, and the entire group of patients with multiple myeloma is subdivided into five clinical stages: stage I = score 0, stage II = score 1, stage III = score 2; stage IV = score 3, stage V = score 4. Significant differences exist between both mean survivals (p less than 0.01), and between the survival curves (p less than 0.0001) within the five scoring clinical stages. PMID- 2602638 TI - [Folate and vitamin B12 deficiency. Characterization of parameters for early diagnosis]. AB - True vitamin B12/folate deficiency is more common than is currently appreciated; it appears in many guises and the classic hematological features of megaloblastic anaemia are often absent. The single most reliable predictor of megaloblastic anaemia is serum vitamin B12/folate concentration, but this determination in a screening program for all patients is difficult in terms of laboratory overload and cost. Early recognition of nutritional anaemias is, however, mandatory and we undertook this study to explore the possibility of identifying, on a demographic basis or because of routine laboratory results, a group of subjects at risk for vitamin B12/folate deficiency. Results obtained in simultaneous radioassay of serum B12 and folate levels and erythrocyte folate concentration in 1.200 hospitalized patients are presented. Coexisting iron deficiency was excluded by ferritin assay. We found no significant difference between males and females and no correlation between serum folate and B12 concentrations and aging. Low serum folic and cobalamin levels were found in 53% of patients with macrocytosis and elevated MCH, even in the absence of anaemia. These observations suggest that increased MCV and MCH may be present before a related anaemia and that serum folate and cobalamin levels must be monitored early in these patients to prevent a deficiency. PMID- 2602639 TI - [In vitro effects of morphine and opioid peptides on neutrophil granulocyte aggregation and ATP release]. AB - The effects of morphine and opioid peptides on neutrophil aggregation and ATP release were studied. Inhibition of human granulocyte aggregation and ATP release was observed in the presence of morphine in a naloxone stereoselective manner, whereas the opioid peptides were ineffective. The effects of DAGO, DADL and Dynorphin 1-9 on the granulocyte aggregation and ATP release were also evaluated, but these opioids peptides are unable to modify neutrophil function. Our studies confirm the role of mu receptors on modulation of polymorphonuclear granulocyte aggregation and suggest a key role of opioid peptides in the regulation of some immune system functions. PMID- 2602640 TI - [Presentation of 2 clinical cases of deficiency of granulocyte membrane glycoproteins]. AB - Two cases of moderate granulocyte adhesion glycoproteins complex deficiency are briefly discussed. These patients presented a clinical history of serious infections at various tissues and organs. Recently, the studies with monoclonal antibodies identified a new group of congenital granulocyte diseases. PMID- 2602642 TI - New aspects in the diagnosis and treatment of Hodgkin's disease. Proceedings of the First International Symposium on Hodgkin's Disease. Cologne (FRG), October 2 3, 1988. PMID- 2602641 TI - [Micromolecular multiple myeloma in the testis and subcutaneous tissue]. AB - The Authors describe a case of multiple myeloma characterized by extraskeletal spread at the testis and at the subcutaneous soft tissues. They evaluate the pathogenetic hypothesis and the prognostic significance. PMID- 2602643 TI - Radiolabeled monoclonal antibodies against Reed-Sternberg cells for in vivo imaging of Hodgkin's disease by immunoscintigraphy. AB - The Hodgkin Reed-Sternberg (HRS-1) monoclonal antibody (Mab) was raised against the L 428 Hodgkin's disease (HD) cell line. The HRS-1 Mab was labeled with radioactive iodine and injected into six patients with Hodgkin's disease of varied histological subtypes for immunoscintigraphic imaging. In five patients, the HRS-1 Mab was labeled with 131I; a control anti-alpha-fetoprotein (AFP) Mab was injected simultaneously in two of these five cases. Four of five patients had a positive scan (nodal, splenic and hepatic involvements), the results in the fifth patient being equivocal. In the sixth patient, the HRS-1 Mab was labeled with 123I in order to utilize tomoscintigraphy instead of linear scintigraphy. Although the immunoscintigraphy (IS) was performed secondary to effective chemotherapy, images of bony disease were demonstrated. These preliminary results demonstrate that IS with iodine-labeled HRS-1 Mab is feasible and informative in Hodgkin's lymphoma. The real clinical value and the specificity of IS deserves confirmation in a larger series of patients. Several techniques such as the use of Fab or F(ab')2 fragments should further improve the results. PMID- 2602644 TI - Diagnostic strategies and staging procedures for Hodgkin's lymphoma: bone marrow scintigraphy and magnetic resonance imaging. PMID- 2602645 TI - Two cycles of MOPP and definitive radiotherapy for stage IIIA and IIIB Hodgkin's disease. PMID- 2602646 TI - High-dose combination chemotherapy with cyclophosphamide, carmustine, etoposide, and autologous bone marrow transplantation in 60 patients with relapsed Hodgkin's disease: the M. D. Anderson experience. PMID- 2602648 TI - Preliminary results of autologous bone marrow transplantation in the management of resistant Hodgkin's disease: experience of the Bloomsbury Transplant Group at University College, London. PMID- 2602647 TI - Treatment of resistant Hodgkin's lymphoma with bone marrow transplantation in Italy. PMID- 2602649 TI - DNA gene rearrangement studies in Hodgkin's disease and related lymphomas: a contribution to their cellular origin. PMID- 2602650 TI - Risk of secondary acute leukemia and preleukemia after Hodgkin's disease: the Institut Gustave-Roussy experience. AB - From 1960 to 1984, 871 patients were treated for Hodgkin's disease at the Institut Gustave-Roussy. Twenty-six percent of the cohort were treated with radiotherapy (RT) alone, 6% with chemotherapy (CT) alone, and 68% with a combination of RT and CT, either at first line or for salvage treatment. MOPP chemotherapy was given to 42% of the patients. Overall, 19 secondary acute leukemias or preleukemias were observed, 3 of them after extended RT alone, the other 16 after a combination of RT and MOPP. Among the alkylating agents used, only nitrogen mustard (mechloretamine) was shown in a multivariate analysis to be significantly associated (P less than 0.001) with an increased risk of secondary leukemia. A dose response was observed, with the risk relative to general population incidence rates being 45 in patients having been treated with 1-59 mg (total dose) of nitrogen mustard, 211 in those treated with 60-119 mg, and 636 in those treated with greater than or equal to 120 mg. No other factors were found to be associated with leukemia risk. The 10-year cumulative incidence of leukemia was zero in patients treated with limited RT alone, 2.4% in those treated with extended RT alone, 0% in those treated with a combination of RT and CT without nitrogen mustard, and 12.4% in those treated with RT + nitrogen mustard. Whether other alkylating agents give a similar result remains to be determined; these data suggest that the use of nitrogen mustard at a higher total dose than 60 mg is questionable in the treatment of Hodgkin's disease. PMID- 2602651 TI - Phenotypic and genotypic analysis of two cell lines derived from Hodgkin's disease tissue biopsies. PMID- 2602652 TI - Characterization of Hodgkin's disease derived cell line HDLM-2. AB - The cell line HDLM-2 was established from the pleural effusion of a patient with Hodgkin's disease. Here, we describe the morphological, cytochemical, enzymological, immunological, molecular biological, and functional characteristics of the cell line. The results of this multiparameter profile show that HDLM-2 is different from other well-studied leukemia-lymphoma cell lines including other Hodgkin's disease derived cell lines. HDLM-2 cultures contain mainly mono- or binucleated cells, but also prominent giant cells with two to ten nuclei. HDLM-2 cells do not express an immunophenotype characteristic of a given cell lineage. However, the cells are positive for Ki-1, HeFi-1, Leu-M1, Tac, and HLA class II markers. Cytochemical, enzymological, and functional data are equally inconclusive, but are definitely not compatible with a monocyte/macrophage profile. Analysis of the gene status documents that T-cell receptor beta- and gamma-chain genes are rearranged while immunoglobulin heavy chain genes are in germline configuration. The combined results indicate a T-cell origin of HDLM-2 cells. The evidence available from this and other established Hodgkin's disease derived cell lines suggests a lymphoid origin of Hodgkin and Reed-Sternberg cells. PMID- 2602653 TI - A new hypothesis on the cellular origin of Reed-Sternberg and Hodgkin cells based on the immunological and molecular genetic analysis of the KM-H2 line. PMID- 2602654 TI - Effects of l-carnitine on membrane potential derangements induced by palmitoylcarnitine and anoxia in isolated superfused guinea-pig papillary muscle. AB - We examined in isolated superfused guinea-pig papillary muscle whether palmitoylcarnitine caused electrophysiological derangements similar to those caused by anoxia, and whether l-carnitine was similarly effective in improving membrane potential characteristics in both cases. Superfusion with Krebs Henseleit solution containing 3 x 10(-4) M palmitoylcarnitine for 30 min caused gradual reduction of resting membrane potential and amplitude of action potential, and marked shortenings of the duration of action potential and absolute refractory period. On the other hand, aeration with 95%N2-5%CO2 for 30 min caused the same electrophysiological changes as those caused by palmitoylcarnitine. In both deteriorated preparations with palmitoylcarnitine superfusion and with 95%N2-5%CO2 aeration, l-carnitine (3 x 10(-3) M) prevented the papillary muscle from these derangements and restored the membrane potential at 10(-2) and 3 x 10(-2) M. It is concluded from these results that acylcarnitines such as palmitoylcarnitine, the accumulation of which has been thought to inhibit oxidative phosphorylation in ischemic heart, induce electrophysiological derangements quite similar to those found under anoxia, and that the application of l-carnitine is an effective solution to improve the electrophysiological derangements. PMID- 2602655 TI - Lack of dose proportional pharmacokinetics for CI-937, an anthrapyrazole DNA intercalator, in mice. AB - The time course of CI-937, an anthrapyrazole DNA intercalator, was studied in plasma of mice after single intravenous doses of 1.2, 8, 12, and 15 mg/kg (1/10 the LD10, 2/3 the LD10, LD10, and LD50). CI-937 concentrations in plasma were determined by a sensitive radioimmunoassay capable of quantifying 0.1 ng/ml. Area under the plasma concentration-time curve increased less than proportionally to dose. Time-averaged plasma clearance was dose-dependent, increasing from 31.1 to 63.6 ml/min/kg over the 1.2 to 12 mg/kg dose range. Terminal half-life in plasma ranged from 11 to 25 days. Fraction plasma protein bound was 69 to 76% from 10 to 10,000 ng/ml, which suggests the nonlinear behavior was not due to saturable protein binding. Potential mechanisms include autoinduction of metabolism and dose-dependent reabsorption from the gastrointestinal tract or kidneys. PMID- 2602656 TI - Persistent desensitization of the heart to the inotropic action of isoproterenol by adenosine. AB - Isolated guinea pig hearts were perfused with Krebs buffer in the absence or presence of 10 microM adenosine for 60 to 120 min followed by a 15 min washout with adenosine-free buffer. The effects of isoproterenol on left ventricular dP/dt and heart rate were then determined. Perfusion with adenosine for a minimum of 90 min followed by washout resulted in a 40% depression of the dose-response curve of left ventricular dP/dt to isoproterenol. This depressed inotropic responsiveness persisted for at least 1 hr after cessation of adenosine perfusion. The heart rate response to isoproterenol was unaffected. Also, adenosine perfusion had no effect on ouabain inotropism. Measurement of adenosine in coronary effluent and in ventricular tissue by radioimmunoassay verified that no residual elevated adenosine remained following perfusion and washout. Moreover, isoproterenol-induced release of adenosine into the coronary effluent did not differ between control and adenosine-treated hearts. Addition of 100 microM theophylline, an adenosine receptor antagonist, to the adenosine containing buffer during perfusion prevented the depressed response to isoproterenol. In membrane fractions prepared from ventricles, beta receptors were assessed by (-) [125] iodocyanopindolol binding and neither the density of these receptors nor their affinity for agonists or antagonists was altered by adenosine perfusion. However, activation of adenylate cyclase by isoproterenol (10 microm) was significantly depressed in membranes from adenosine perfused hearts. These findings are consistent with a receptor mediated action of adenosine to produce persistent depression of catecholamine inotropism. Such an effect may be important in heart failure where myocardial levels of adenosine are elevated and circulating levels of catecholamines are high. PMID- 2602657 TI - Metabolism and disposition of (R)-4-[3-(2-hydroxy-2-phenyl)ethylamino-3 methylbutyl]benzamide Hcl (LY 195448) in rodents. AB - The disposition and metabolism of (R)-4-[3-(2-hydroxy-2-phenyl)ethylamino-3 methylbutyl]benzamide HCl, or LY 195448 (LY), were studied in rodents 1 hr following a single iv injection of 14C-LY at 30 mg/m2 (10 mg/kg mice and 5 mg/kg rats), In all tissues and carcases, recovery of 14C was nearly complete. The majority of radioactivity was recovered from intestine (40%) whereas liver and urine accounted for 10% each, kidney for 3-5%, and plasma for 1-3% of total administered radioactivity. Analyzing by HPLC and TLC, para-hydroxy-LY (para-OH LY) in addition to unchanged drug, was found in all tissues. Meta-OH-LY was detected only in urine, intestine and kidney. These metabolites were found to be conjugated with either glucuronide or sulfate moieties. Peaks coeluting with authentic para-OH-meta-methoxy-LY and di-OH-LY were also observed. PMID- 2602658 TI - Urinary O6-methylguanine excretion in the rat after O6-methylguanine but not N methylnitrosourea administration. AB - Urinary makers that permit monitoring the exposure of rats to methylating carcinogens could be of considerable value. Because of the association of the formation and retention of O6-methylguanine (m6Gua) with carcinogenesis, the urinary recovery of this compound would be of particular interest. Urine of rats receiving 200 muCi 3H-methyl nitrosourea (MNU) was therefore subjected to HPLC analysis to detect labeled m6Gua. Following the intraperitoneal injection of 3H MNU (16 or 80 mg/kg), 3H-m6Gua could not be detected in the urine, although its presence was demonstrated in liver DNA under such conditions. Rats were also administered 3H-MNU followed by pretreatment with unlabeled m6Gua to block the repair enzyme, m6G-DNA-transmethylase, which might have obscured an excision mechanism. This procedure permitted the recovery of about half of the administered dose of m6Gua in the urine, but none of this compound contained tritium. We conclude that m6Gua, though formed in the DNA from MNU, is not excised and excreted as such in the urine. Thus m6Gua could not be used to serve as a suitable urinary marker for exposure to methylating carcinogens. PMID- 2602659 TI - Biotransformation activities in Clara and alveolar type II cells isolated from hamster lungs. AB - A method is described for isolation of enriched preparations of nonciliated bronchiolar epithelial (Clara) and alveolar type II cells from hamster lungs. Clara cells were enriched to 48% (1.7 +/- 0.7 x 10(5) cells per hamster), and type II cells to 86% (3.4 +/- 1.7 x 10(6) cells per hamster). Analysis of biotransformation activities indicated concentration of 7-ethoxycoumarin deethylase activity in Clara cells, whereas glutathione S-transferase was more widely distributed among cell types, with highest activity in type II cells. The significance of differential cellular localization of activation and detoxification activities to susceptibility to pulmonary toxicants, is discussed. PMID- 2602660 TI - Hyaluronic acid metabolism in inflamed mesenterium of guinea pig. AB - Hyaluronic acid is known to play an important role in tissue remodeling and inflammatory process. To clarify the metabolism of hyaluronic acid in peritonitis, the biosynthesis of glycosaminoglycans in mesenterium was investigated in caseinate-induced peritonitis in guinea pig. Mesenterium showed acute inflammatory changes with polymorphonuclear leukocyte infiltration and produced much hyaluronic acid with a high molecular weight. Radioautography of inflamed tissue incubated with (3H)glucosamine demonstrated that radioactivity was incorporated predominantly by mesothelial cells and fibroblasts in the submesothelial cell layer. Intraperitoneal injection of human recombinant interleukin-1 alpha induced intraperitoneal accumulation of hyaluronic acid and its production by mesenterium. Heatlabile stimulating factor(s) for the biosynthesis of hyaluronic acid was present in the peritoneal fluid of inflamed guinea pigs. These results indicate that mesenterium is a hyaluronic acid producing tissue and inflammatory changes of mesenterium are essential for the initiation and/or stimulation of hyaluronic acid production. PMID- 2602661 TI - Estradiol stimulation of inositolphospholipid metabolism in human endometrial fibroblasts. AB - Stimulated inositolphospholipid turnover has been proposed to constitute a signal transducing mechanism in many cell types. To determine the inositolphospholipid turnover during stimulation by 17 beta-estradiol, the turnover kinetics of phospholipids was investigated in human endometrial fibroblasts. In cells incubated with [32P] phosphate for 1 h, estradiol rapidly and persisitently (for at least 30 min) enhanced the rate of 32P-labeling of phosphatidic acid (PA). On the other hand, after a lag time of 5 min, 32P-labeling of phosphatidylinositol (PI) was also increased also. These sequential 32P-labeling of PA and PI demonstrated that inositolphospholipid turnover was stimulated in fibroblasts exposed to estradiol. The rapid estrogen-stimulated inositolphospholipid turnover may not be through the mechanism associated with classical action of estrogen. PMID- 2602662 TI - Experimental studies on the toxicity of some compounds isolated from Ferula communis in the rat. AB - The antithrombinic activity of some naturally occurring omega-oxygenated derivatives of ferulenol and ferprenin has been tested. On the basis of these results, both the type of the oxygenated function and the stereochemistry of the terminal double bond seem important for the biological activity. PMID- 2602663 TI - Responses of upper-airway dilating muscles and diaphragm activity to end expiratory pressure loading in anesthetized dogs. AB - The steady-state responses of upper-airway dilating muscles and diaphragm activity to elevation of lung volume induced by positive end-expiratory pressure loading were studied in 9 pentobarbital-anesthetized dogs with vagus nerves intact. The early and late effects of 5 min of expiratory threshold loads upon upper airway dilating muscle activity (the alae nasi, the genioglossus and the posterior cricoarytenoid) were compared to their effects on diaphragm activity. During resting O2 breathing, application of 5 and 10 cm H2O of positive end expiratory pressure produced no significant change in the peak electrical activity of the upper-airway dilating muscles and diaphragm (p greater than 0.05). No qualitative differences were found in the upper-airway dilating muscles and diaphragm responses to expiratory threshold loads when the animals breathed 3 or 7% CO2 in O2, compared to when they inspired 100% O2. Furthermore, no differences were found in the electrical activity of the upper-airway dilating muscles and diaphragm at any given end-tidal CO2 when unloaded responses were compared with loaded responses during progressive hypercapnia. However, positive end-expiratory pressure loading caused significant prolongation of expiratory duration, which gradually returned toward control levels when the loads were maintained. In animals who developed periodic breathing by increasing levels of anesthesia, positive end-expiratory pressure loading eliminated the periodicity and made the pattern of breathing regular. Based on these results, it can be concluded that under the conditions of these experiments, increases in lung volume produced by expiratory threshold loads do not reduce the activity of upper airway dilating muscles. The maintenance of the electrical activity of the upper airway dilating muscles might be caused by excitatory reflex mechanisms or central habituation. PMID- 2602664 TI - Surgical treatment of gastroesophageal reflux in ten patients with severe asthma. AB - The surgical cure of gastroesophageal reflux was investigated in 10 asthmatic adults with a mean post-operative follow-up period of 21 months. The patients had severe asthma, and gastroesophageal reflux confirmed by 3-hour post-prandial pH monitoring. Medical treatment for reflux was effective on the clinical signs of the reflux but ineffective on the respiratory signs. The clinical course of the asthma, and 3-hour post-prandial pH monitoring were evaluated before 3, 6, and after 6 months. The reflux was cured by surgery in 8 cases, and improved in two. Immediate post-operative surveillance of the asthma revealed no cure. There were three immediate failures, and two recurrences before 6 months post-operative. Improvement was stable beyond 6 months in 5 patients (suppression or 80% reduction of corticosteroids in 3 cases, considerable reduction in the use of bronchodilators in 2 cases). Our results suggest that the surgical treatment of gastroesophageal reflux may be useful, at least for suppressing an aggravating factor in the respiratory illness. PMID- 2602665 TI - Role of the mediastinum as a part of the chest wall: analyzed by computed tomography. AB - Using computed tomography (CT), geometrical changes in pulmonary structures in 4 human volunteers were analyzed. A series of parallel transaxial CT scans of the lung were obtained for each volunteer while he held his breath at maximal inspiration and maximal expiration. Changes in pulmonary structures were evaluated by comparing the maximal inspiration scans for each slice position. The longitudinal displacement of the lung volume was categorized as either a rib cage displacement or a diaphragm-abdominal displacement. The ratio of diaphragm abdominal contribution to vital capacity was 0.49-0.65 for the volunteers. The thoracic volume displacement was categorized as either a mediastinal displacement or a rib cage displacement. The former was considerably larger than the latter. Since the rostral end of the mediastinum is fixed to the thoracic cage and the caudal end is fixed to the diaphragm, we conclude that the mediastinum-diaphragm boundary converts the axial force generated by the diaphragmatic excursion into radial force. PMID- 2602666 TI - Acute respiratory distress syndrome with pulmonary calcification in two patients with B cell malignancies. AB - Two patients, one with B cell lymphoma and hypercalcemia and the other with multiple myeloma and hypercalcemia developed acute progressive respiratory insufficiency characteristic of the adult respiratory distress syndrome (ARDS). Both were intubated and placed on mechanical ventilation. Lung compliance deteriorated and became refractory to mechanical inflation. Examination of the lungs at post mortem examination disclosed widespread calcification within alveolar septa and diffuse alveolar damage with hyaline membrane formation consistent with ARDS. Although ARDS has been described with lymphomatous involvement of the lungs, its development in association with metastatic calcification in B cell malignancy has not been previously reported. PMID- 2602667 TI - Penicillamine for interstitial lung disease in rheumatoid arthritis. PMID- 2602668 TI - Retrospective studies in scleroderma: pulmonary findings and effect of potassium p-aminobenzoate on vital capacity. AB - The principal clinical pulmonary findings were extracted from University of Michigan Hospital records of 390 patients with scleroderma. Dyspnea was the most frequent symptom and strongly correlated with pulmonary fibrosis and with decreased vital capacity (FVC) and CO diffusing capacity (DLCO). The mean value for FVC was 84% of the predicted normal for 326 patients, and that of the initial DLCO 56.8% of the predicted normal (323 patients). Pulmonary fibrosis was diagnosed on first chest X-ray in 80 of 382 patients. An additional 48 patients developed fibrosis detected on subsequent X-rays. Analyses were performed to determine whether the deterioration of pulmonary function over time was less for scleroderma patients who were adequately treated with potassium p-aminobenzoate (KPAB) than for those inadequately or never treated with KPAB, The average decrease for both FVC and DLCO was found to be less for KPAB-treated patients. However, only in the case of vital capacity was the difference significant. In the presence of radiological evidence of pulmonary fibrosis FVC decreased more rapidly (p = 0.002), but the decline in DLCO was not affected. When adjusting for the presence or absence of fibrosis the average slopes of the logarithm of vital capacity were significantly less negative (p = 0.003) for patients on KPAB. PMID- 2602669 TI - Resistance measurement in normal and obstructed excised human lungs by means of the interrupter method. AB - In 6 normal and 7 obstructed excised human lungs the interrupter resistance (APTA, Jaeger Company) with an airway occlusion period of 100 ms was determined, by measuring the equivalent of the alveolar pressure at the end of the occlusion period. To check the pressure equilibration between the tracheal pressure and the alveolar space, catheters were put in the most peripheral layer of the lung. The lungs were ventilated in an artificial thorax. The airway resistance determined from the transbronchial pressure difference by the catheters was taken as a reference. Compared with the reference method, an overestimation of the airways resistance by the interrupter technique in normal lungs was found which was caused by an overshoot of the pressure equilibration during the occlusion period. In contrast, in severely obstructed lungs the pressure equilibration was not complete which led to an underestimation of the airways resistance by the interrupter technique. The best approximation of the airways resistance by the interrupter method was found in lungs with a low degree of obstruction. PMID- 2602670 TI - Total respiratory resistance in chronic obstructive pulmonary disease. AB - Using a recently described automated system, we measured total respiratory resistance (Rrs) of 59 patients with obstructive lung disease during spontaneous tidal breathing. We also measured airway resistance (Raw) and various other indices of pulmonary function. The results demonstrate that this system gives values of Rrs which correlate well with other objective measures of the severity of obstructive lung disease. It can also be used to detect changes in resistance after inhalation of a bronchodilator. In 10 patients we measured Raw during tidal breathing and computed the total non-airway resistance (Rnaw) as the difference between Rrs and Raw. Rnaw made up a larger portion of Rrs than would be expected in these patients. These results could not be accounted for by differences in breathing frequency, and may instead have been caused by differences between the times in the ventilatory cycle at which Rrs and Raw were measured. We cannot exclude the possibility that Rnaw was abnormally elevated in these patients. PMID- 2602671 TI - Effect of cold pressor test on carbon monoxide diffusing capacity in normal subjects. AB - We investigated changes in the pulmonary carbon monoxide diffusing capacity (DLco) during the cold pressor test (CPT) on 25 normal subjects. In 10 of them we also observed changes in circulatory parameters by a computerized dual cadmium telluride detector system, using an equilibrium radionuclide blood-pool label. DLco and DLco per unit of alveolar volume (DLco/VA) averaged in the control period were 29.4 +/- 4.1 ml/min/mm Hg, 6.1 +/- 0.8 ml/min/mm Hg/l (mean +/- SD). During the 2nd minute of CPT, DLco increased by 3.6 +/- 1.5% and DLco/VA by 5.1 +/- 1.5% (mean +/- SE). The systemic blood pressure increased by 17% (mean increase) whereas the heart rate and the stroke volume remained unchanged. The increases were small but significant (p less than 0.05, p less than 0.01, respectively). We conclude that the increase in DLco is due to cold-induced systemic vasoconstriction followed by a passive shift of blood into the pulmonary vasculature. PMID- 2602672 TI - [Budd-Chiari syndrome: the introduction of surgery]. PMID- 2602673 TI - [Clinical features of Budd-Chiari syndrome]. PMID- 2602674 TI - [Radical correction of Budd-Chiari syndrome]. PMID- 2602675 TI - [Surgical treatment of Budd-Chiari syndrome]. PMID- 2602676 TI - [Correlation between the function and structure in papain-induced emphysema in dogs]. AB - To examine the relationship between morphologic changes and the alteration of pulmonary function, papain solution was administered to 11 dogs by inhalation and to 5 dogs by a single intratracheal injection. Pulmonary function tests, including determination of lung volume subdivision, diffusion capacity (DLCO), pressure-volume relationship of the lung and arterial blood gas were performed before and after papain treatment. The dogs were then killed and the lungs processed for pathologic studies. The severity of emphysema was graded as percent of emphysema according to Dunill's method and we compared this to the antemortem pulmonary function data. Exponential constant K was determined by fitting lung pressure-volume data to the equation V = Vo (1-e-KP). After papain administration, DLCO decreased, K of the pressure-volume curve increased, and arterial blood oxygen pressure reduced significantly. The changes of residual volume, the ratio of residual volume to total lung capacity, DLCO per unit lung volume, and the values of the exponential functions of pressure-volume data were correlated with the severity of emphysema with statistical significance, but none of them showed excellent order correlation. Multiple regression equation using 2 to 4 of the parameters indicated that the severity of emphysema can be predicted more accurately. We conclude that recognition of the severity of emphysema requires a multivariate approach including the determination of lung volume, DLCO, and pressure volume relationship of the lung, because the relationship between the severity of emphysema and the values obtained with these measurements are nonlinear. PMID- 2602677 TI - [Preoperative evaluation of digital subtraction pulmonary angiography in primary lung cancer]. AB - The preoperative evaluation of the resectability for primary lung cancer was studied by using digital subtraction pulmonary angiography (DSA-PAG). Thirty operative cases with primary lung cancer performed DSA-PAG as preoperative test at random for 3 years from June 1985 were subjected in this study. The apparatus used is DSA device (Angiotoron) of a product of Siemens Co., Ltd. The findings obtained by DSA-PAG were retrospectively studied according to the surgical findings, operative modes and postoperative histopathological findings. Moreover, at the same time, usefulness of DSA-PAG was evaluated comparing its findings with preoperative enhanced CT interpretation. The useful findings were obtained in 10 cases of 30 cases (33%). Its contents were 2 cases with invasion of the left atrium, 2 cases with invasion of superior and inferior pulmonary vein, 5 cases with invasion of truncus pulmonary artery and 1 case with interlobar invasion. The findings in all cases were superior to those obtained by the enhanced CT. The decision of operative modes confirming invasion of tumor or metastatic lymph node is one of the important aims of the preoperative test. DSA-PAG can be carried out simply and safely on out-patient basis, additionally, favorable result can be especially obtained in invasion lesions of blood vessels of hilus regions. From the result, informations of regions unknown by preoperative CT were accurately obtained. As a rule, DSA-PAG should be performed by the preoperative routine test of primary lung cancer. PMID- 2602678 TI - [Quantitative assessment of arterial capacitance in human by noninvasive method]. AB - The purpose of this study was to determine the magnitude of arterial capacitance in human by noninvasive method. In 60 patients (Age: 62.1 +/- 13.4 years) without cardiovascular disease first-pass radionuclide angiography was performed using a digital gamma camera to calculate cardiac output and stroke volume (SV). Systolic interval (ts), diastolic interval (td) and arterial blood pressure were measured using ECG, phonocardiography and sphygmomanometer. We assumed a simple model in which all capacitance (C) lumped into one site with a resistance (R) in parallel to the C. C was calculated by the following basic equations. (Formula; see text) arterial diastolic pressure, E: left ventricular external work. Our results showed: 1) Arterial capacitance ranged from 0.38 ml/mmHg to 2.10 ml/mmHg and more than 60% of stroke volume was pooled in the arterial capacitor during systole. 2) Arterial capacitance fell linearly with age (C = 2.37-0.02 x Age, r = -0.680, p less than 0.001). It is concluded that the capacitor played an important role in arterial circulation. PMID- 2602679 TI - [Clinical effects and plasma concentration levels of aprindine hydrochloride in patients with tachyarrhythmias]. AB - Aprindine hydrochloride (aprindine) was administered orally in 17 Japanese patients with supraventricular or ventricular tachyarrhythmias, and the clinical effects and plasma concentration levels were evaluated. The antiarrhythmic effects were defined using Holter ECG recordings. Aprindine was administered orally with a daily dose of 40 mg for 2 weeks in all cases, and aprindine, 60 mg daily, was administered for the next 2 weeks in patients who did not show sufficient antiarrhythmic effects with 40 mg of the drug. Aprindine was effective in 9 of 17 patients, and the mean plasma concentration level reached 0.6 micrograms/ml 2 weeks after the administration was started. Effective results were seen in 2 of the 4 patients receiving a daily dose of 60 mg, and the mean plasma concentration level reached 1.0 microgram/ml 2 weeks after the administration was started. Transient mild elevations of liver transaminases were observed in one patient and mild transient anemia was observed in another. These abnormal data disappeared although the drug administration was continued. In conclusion, the administration of a relatively small dose of aprindine and, consequently, low plasma concentration levels, are effective for cardiac tachyarrhythmias in Japanese patients. PMID- 2602680 TI - [A case of myocardial infarction due to the left main trunk lesion, in which percutaneous coronary recanalization and emergency coronary-aorto bypass graft, and subsequent percutaneous coronary angioplasty were effective not only from a viewpoint of survival but from comeback to social life]. AB - A case of acute myocardial infarction due to the lesion in the left main coronary artery was reported. A 50-year male was referred to our department for suspected acute myocardial infarction. Physical examination on admission revealed slight cyanosis with cold sweating due to severe chest pain. Pulse was irregular and heart rate was 78 beats/min. Blood pressure was 100/80 mmHg. A series of electrocardiograms (ECG) and laboratory data provided the diagnosis of wide ranged anterolateral infarction in the left ventricle. Emergency coronary angiograms taken without delay showed a subtotal occlusion (99% stenosis) of the left main coronary trunk (LMT) before the initiation of intracoronary thrombolysis (PTCR). Following the intracoronary infusion of urokinase of 1,200,000 units, symptoms and ECG changes transiently improved but worsened later, and LMT stenotic lesion and delayed filling of myocardium were similar with before PTCR. Emergency coronary-aorto bypass graft (CABG) was undertaken without a significant delay to both the left anterior descending artery (LAD) and left circumflex coronary artery (LCX). With these treatments, the patient could survive despite the wide area of infarction due to LMT lesion. Coronary angiograms performed 37 days after the CABG showed that the graft to LAD was completely occluded and the LCX graft was patent with partial stenosis. Treadmill test at this time induced an anginal episode with ischemic ECG changes on moderate exercise, indicating the presence of significant area of ischemic myocardium. For salvage of the ischemic myocardium, percutaneous transluminal coronary angioplasty (PTCA) was successfully performed for the LMT stenosis, resulting in no episode of angina nor ischemic ECG changes during exercise loading.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602681 TI - [Cardiac surgery of tetralogy of Fallot associated with DiGeorge syndrome: a case report]. AB - A case of 7-year-old boy with tetralogy of Fallot associated with DiGeorge syndrome was reported. He had been diagnosed as cardio-facial syndrome with hypoparathyroidism because of hypocalcemia, convulsion, cardiac defect and the characteristic face. But immunologic study showed hypofunction of cellular immunity and cardiac catheterization and angiogram revealed the Tetralogy of Fallot. So we diagnosed as DiGeorge syndrome and performed operation. The thymus was not found and we close the ventricular defect with patch and reconstructed right ventricular outflow tract with transannular patch. We often measured serum ionized calcium level and corrected with calcium gluconate intravenously. Peritoneal dialysis was done due to oliguria and much inotropic support was necessary. PMID- 2602682 TI - [A case of primary pulmonary hypertension with beneficial effect of oral long acting prostaglandin E1 and nifedipine]. AB - A 23-year-old female with moderate primary pulmonary hypertension (PPH) was treated by chronic oral administration of long-acting prostaglandin-E1 (PGE1) and nifedipine. Cardiac catheterization revealed evidence that both drugs had beneficial effects on this case. Total pulmonary resistance (TSR) decreased from 1089 to 955 dyne.sec.cm-5 by intravenous administration of PGE1 at a rate of 0.04 micrograms/kg/min and from 1089 to 710 dyne-sec-cm-5 by sublingual administration of nifedipine 10 mg respectively. After ten months of treatment with these two drugs, her pulmonary arterial pressure decreased from 85/40 (mean; 58) mmHg to 55/36 (mean; 45) mmHg, TSR decreased from 1089 to 829 dyne.sec.cm-5 and PaO2 in room air increased from 74.5 to 94.9 mmHg. Chest X-P and ECG revealed the decrease in the loading of the right ventricle. Thus, combined administration of PGE1 and nifedipine is expected to benefit PPH. PMID- 2602683 TI - Laser microprobe mass spectrometry (LAMMS) analysis of beryllium, sarcoidosis and other granulomatous diseases. AB - Beryllium was detected in the granulomas of all thirty-three cases of CBD examined and was absent in thirty cases of sarcoidosis. It was also found in association with coal dust in one of twelve normal lungs. Beryllium could also be detected in Schaumann bodies and hyalinized scars. Beryllium, though sometimes present in Kveim negative biopsies of CBD patients, was not found in any originating Kveim antigen. Rare earths (La, Ce, Pr and Nd) were unexpectedly found in two of the thirty sarcoid patients but not in any other samples. We have identified the crystalline component of Schaumann bodies as calcite and shown that they, as well as calispherules of microlithiasis, contain calcium phosphate. Al and Ti may be found in normal lungs but when associated with hypersensitivity granulomatous disease, their oxides were also present. PMID- 2602684 TI - Immunoregulatory proteins in bronchoalveolar lavage fluid. A comparative analysis of pigeon breeders' disease, sarcoidosis and idiopathic pulmonary fibrosis. AB - Bronchoalveolar lavage fluid (BALF) cell profiles, interleukins 1 and 2, (IL-1 and IL-2) and soluble interleukin 2 receptor (IL-2R) levels from patients with pigeon breeders' disease (PBD) (n = 24) and asymptomatic pigeon breeders (n = 10) were compared with those from patients with active sarcoidosis (n = 11), inactive sarcoidosis (n = 10), idiopathic pulmonary fibrosis (n = 25) and normal subjects (n = 10). BALF total cells, lymphocytes and OKT4 receptor-bearing lymphocytes/ml were higher in PBD and active sarcoidosis compared with normals (P less than 0.02 all comparisons). In the asymptomatic pigeon breeders bronchoalveolar (BA) lymphocyte numbers/ml were higher than controls (P less than 0.01) producing a subclinical lymphocytic "alveolitis" in 80% of subjects, although compared with symptomatics, % OKT4 (helper) cell numbers were lower (P less than 0.05). OKT4/OKT8 ratios in both groups were normal, whereas in active sarcoidosis ratios were higher (P less than 0.05) but with considerable overlap. Mean levels of IL-1 and IL-2 were raised in the BALF from all groups compared with normals (P less than 0.01 all comparisons), IL-2 being higher in active sarcoidosis and IPF compared with PBD (P less than 0.01). There was no significant difference in detectable BALF soluble IL-2R between patient groups, although its levels correlated positively with IL-1 (22 paired samples from all groups (rs = 0.8, P less than 0.02) and negatively with % and T-lymphocytes/ml in PBD (rs = 0.75, P less than 0.02, rs less than 0.8, P less than 0.01). However, when BALF soluble IL-2R is expressed in terms of T lymphocytes/ml of epithelial lining fluid (ELF), asymptomatic pigeon breeders had significantly higher levels than their symptomatic counterparts (P less than 0.01). It is concluded that percentage lymphocytes [corrected] are similar in both groups of pigeon breeders, although those with PBD had increased numbers of OKT4 (helper) cells. Patients with active sarcoidosis could not be reliably differentiated from those with acute PBD on the basis of BAL cell profiles. Our results suggest that IL-1 leads to soluble IL-2R formation and that continued antigenic stimulation, as with inhaled pigeon allergens, results in a down regulation of BALF IL-2. Excess BALF soluble IL-2R on a cellular basis suggests a mechanism by which some pigeon breeders remain asymptomatic. PMID- 2602685 TI - Biochemical and immunological parameters of sarcoid patients in west Greece. AB - Sera from 55 patients with inactive and active sarcoidosis were analyzed for biochemical and immunological serum factors (immunoglobulins, complement and autoantibodies). These parameters of sarcoid Greek patients are presented for the first time in the literature. They are compared with similar findings in the European and World literature. Summarily the IgM rheumatoid factor (RF) and C4 levels were increased in both sarcoidosis groups. These data suggest that the underlying etiological events of sarcoidosis do exist at a subclinical level. PMID- 2602686 TI - Epidemiological study on sarcoidosis in Japan. Recent trends in incidence and prevalence rates and changes in epidemiological features. AB - This paper presents the results of an investigation made on the recent trends in the estimated prevalence and incidence rates of sarcoidosis in Japan and the changes in its epidemiological characteristics based on the results of nation wide surveys conducted in 1972 and 1984. Age-adjusted mortality trends based on vital statistics were also examined. The estimated prevalence rate in males increased from 3.0 per 100,000 population in 1972 to 3.8 in 1984 and in females from 3.3 to 5.6, respectively (p less than 0.01), while the estimated incidence rate remained unchanged (1.2 per 100,000 in males and 1.4 in females). The age adjusted mortality rate showed a gradually decreasing tendency from 0.2 to 0.1 per million. The estimated age-sex specific prevalence and incidence rates showed a pronounced increase in the middle-aged and elderly age groups particularly in females but a marked decrease in those 19 years and under. The increase in prevalence rate may be attributable to the prolonged duration of the disease. Noteworthy changes in the pattern of the disorder included a marked increase in the proportion of patients with eye lesions (males: from 31.3% to 44.4% and females: 41.6% to 58.7%) indicative of poor prognosis and statistically insignificant increase in pulmonary parenchymal lesions (males: from 38.1% to 43.4% and females: from 33.5% to 36.4%), the majority of which showed pulmonary mottling not accompanied with severe fibrosis often seen in Europe and America. The standardized prevalence ratios were observed in hot, warm and cold areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602687 TI - An unusual presentation of sarcoidosis in a Korean woman. AB - Sarcoidosis appeals to all specialties in Medicine because of its diverse manifestations and presentations. It commonly involves the lung accounting for much of the disease morbility. The unusual occurrence of radiographic findings with bilateral pleural thickening is discussed. PMID- 2602688 TI - Sarcoidosis following B.C.G. vaccination in a lymphopaenic boy. AB - A case of sarcoidosis in an eleven year-old boy which developed four months following B.C.G. vaccination is presented. This was associated with lymphopaenia of undetermined origin which persisted after the pulmonary lesions subsided. PMID- 2602689 TI - Primary acute pulmonary cavitation in asymptomatic sarcoidosis. AB - Sarcoidosis has a large variety of chest x-ray manifestations, but primary acute cavitation is very rare. We report a case of cavitary sarcoidosis occurring in an asymptomatic 25 year-old white patient. The diagnosis was established from chest x-ray, transbronchial biopsy specimen, bronchoalveolar lavage and gallium 67 scan. The peculiarities of this case are: 1) the presence of hilar adenopathy; 2) the cavitation occurred during the decreased activity of the disease; 3) the resolution of cavity without therapy. We suggest asymptomatic sarcoidosis should be considered in the differential diagnosis of pulmonary cavitation. PMID- 2602690 TI - Peritoneal involvement and ulcerative skin plaques in sarcoidosis: a case report. AB - Sarcoid involvement of peritoneal serosal surface has been documented only in a number of cases and ulcerative skin plaques are distinctly rare. An unique case of systemic sarcoidosis is presented where both these unusual phenomena occurred simultaneously. PMID- 2602691 TI - Sarcoidosis and leukaemia. PMID- 2602692 TI - Healthy singing. PMID- 2602693 TI - Physically efficient string playing. PMID- 2602694 TI - Motion and emotion: a discussion of the interaction between physical motion and human emotion. PMID- 2602695 TI - Dystonia in musicians. PMID- 2602697 TI - Neurologic problems of musicians. PMID- 2602696 TI - Toward a music-medicine dictionary. PMID- 2602698 TI - [Fine structure of the root resorption of human deciduous tooth]. AB - During growth and development of the gnathic bone in infants, it is not possible to observe the processes of resorption of the bone and deciduous tooth root, bone formation and calcification of the permanent teeth separately. In the gnathic bone of infants where a normal balance exists between formation of new tissue and resorption, the formative bone tissue is closely related to the cells which give rise to the deciduous and the permanent teeth. We used a scanning electron microscope to observe the fine structure of the root resorption of the deciduous teeth, using root deciduous teeth extracted from humans. Large and small plate shaped absorbed fossula were found together with projecting dentinal fiber tubuli in the dentinal resorption cavity of the deciduous tooth root. Odontoclasts with a round form supported and covered by fibrous connective tissue were also observed. Furthermore, when the fibrous tissue was removed washed out, an arrangement of calcified collagen fibers (similar to stromal tissue) was found in the cavity. On the absorbed cementum surface a plate-like resorption cavity had formed. The surface was covered by fibrous connective tissue with a regular pattern. The round and oval odontoclasts were surrounded by thick vascular-like connective tissue. High levels of P and Ca were found in the dentinal absorption cavity by X-ray analysis and Al, Mg, Na and Zn were also found. S, P, Ca and Zn were found in the odontoclasts Ca, P, Mg, Na and Zn were found in the cementum resorption cavity. PMID- 2602699 TI - [An acoustical analysis of TMJ sounds and its clinical importance]. AB - The aim of this report was to establish a method for objective examination of TMJ sounds which is required for preventive care of the TMJ dysfunction, and to confirm its clinical importance by means of analysis of mandibular border movement and EMG. The subjects for the acoustical analysis of TMJ sounds consisted of 13 temporomandibular joints as the clicking group, 4 as the crepitus group, and 11 as the control group. The subjects for the analysis of the mandibular movement and EMG consisted of 8 adults with clicking as the clicking group and 11 without TMJ sounds as the control. The results obtained were as follows: 1. Clear and stable TMJ sounds waves could be recorded from the external auditory meatuses. 2. Clicking sounds waves showed a sharper rising and shorter duration than crepitus sounds waves. Comparing the three groups on the basis of the data of power spectrum analysis of frequencies using FFT, the spectrum of frequencies of the crepitus group was the highest and broadest, and that of control group was the lowest. 3. The deviation of the trace of mandibular border movement in the clicking group tended to be larger than in the control group. 4. In the clicking group, the frequency of occurrence of the silent period of EMG bursts during tooth tapping was lower and the duration of the silent period was shorter than in the control group. Duration, interval and cycle of EMG bursts during gum chewing in the clicking group was longer than in the control group. 5. From the above, it was suggested that the ones with TMJ sounds had the TMJ dysfunction latently, therefore it was considered valuable to use an analysis of TMJ sounds in the examination for the preventive care of the TMJ dysfunction. PMID- 2602700 TI - [Effect of iodoform on development of cultured tooth-germs of newborn Syrian hamsters]. AB - To examine the effect of iodoform, widely used as a component of filling sealer for root canals, on differentiation and development of tooth-germs, tooth-germs of second molars from newborn Syrian hamsters were cultivated overnight and treated with various concentrations of iodoform for 48 hours. They were subsequently transplanted into the cheek pouch of Syrian hamsters and were subjected to histo chemical examinations three weeks later. 86% of the seven tooth germs examined survived treatment with 1.0 microgram/ml iodoform, as determined by morphology of tooth-germs. The ratio of survival decreased with increasing doses of iodoform, e.g. 63%, 37%, and 13% for 3.3 micrograms/ml, 6.6 micrograms/ml and 10.0 micrograms/ml iodoform, respectively. In untreated tooth germs, a similar level of survival was obtained with treatment using 1.0 microgram/ml iodoform. Although treatment with 1.0 microgram/ml iodoform showed a survival similar to untreated tooth-germs, the treatment induced a considerable level of aplasia of enamel and dentin in the dental crowns. Meanwhile, higher dose of iodoform was required for induction of aplasia or depression of the dental pulp or root dentain. These results indicate that iodoform over the dose of 1.0 microgram/ml is toxic to cultured tooth-germs of Syrian hamsters and inhibits differentiation or development of the tooth-germs with tissue specificity. PMID- 2602701 TI - [Electromyographic (EMG) electrode impedance and EMG activity from anterior temporal muscle and masseter muscle]. AB - The value and change with time of the impedance of surface EMG electrodes and the effects of their difference between the bipolar electrodes on the electromyographic activity from the anterior temporal muscle and the masseter muscle in six adult male subjects with normal occlusion were studied. The results were as follows: 1. In the anterior temporal muscle, if the impedance of the electrode was under 20 k omega it was stable from just after the electrode disc was applied to the skin. In the masseter muscle, if the impedance was under 30 k omega it became stable within two minutes after the electrode was applied. 2. The difference of impedance between the bipolar EMG electrodes did not correlate with EMG activity. PMID- 2602702 TI - [Comparison between children with missing anterior deciduous teeth and posterior deciduous teeth by analysis of speech sounds]. AB - Growing human offsprings are creatures that communicate by language. If rapidly growing children lose their deciduous teeth very early in life, their language and pronunciation functions may be seriously affected. The authors conducted a series of tests to find how the voice changes when deciduous teeth are extracted. The results may be summarized as follows. 1. There was no significant difference in the formants of vowels on "a-gyo", the first line of the Japanese syllabary, but an appreciable difference was recognized between children (four to six years old) with missing anterior teeth and posterior teeth when there were consonants before and after these vowels. 2. In the formants of the vowels, there was a marked difference in the vowel "i" when children were fitted with no appliance. 3. The strength of voice components in each frequency range was compared between children with missing anterior teeth and posterior teeth. It differed widely in "o ka a sa n" (which means "Mother") and "a-gyo", when children were fitted with no appliance. These findings indicate that the pronunciation of "o ka a sa n" and "a-gyo" can be recovered to some extent if the children are provided with an appliance. However, a sound analysis indicates that their pronunciation ability of sounds on "ka-gyo", "sa-gyo" and "ta-gyo" (the second, third and fourth lines of the Japanese syllabary) can hardly be fully recovered. PMID- 2602703 TI - [A dermaerosion case dealing with a leakage of a chemically irrigable solution (NaOCI solution)]. AB - This paper is a report regarding a dermaerosion case dealing with a leakage of a chemically irrigable solution in a 3 year old boy. We are continuing to observe the dermal changes during as he grows. Also, we carried out a pathological experiment on a rabbit and a patch test of the derm of seven people. The following conclusions were obtained. 1. We observed the dermaerosion of an epithelium repair after a complete elapse of one year. The dermaerosion of the corium could not be repaired but changed the color of the derma of the patient who recovered after a lapse of 2 years and 8 months. 2. We recognized in the rabbit experiment that a 12% H2O2 solution damaged the corium of the rabbit over a period of 24 hours. The 12% H2O2 solution was four times higher, for we normally used a 3% H2O2 solution. 3. When we used a 10% NaOCl solution (which we usually use in the widening of the root canal) for 20 minutes on the derma of the rabbit, the derma damaged the epithelium but over a period of 40 minutes the solution we used on the derma of the rabbit damaged the corium. 4. When we used a NaOCl and H2O2 solution the reaction on the skin of the rabbit is weaker than when only one solution was used. 5. We used 0.5% NaOCl and 0.3% H2O2 solutions for the biceps of 2 atopic diseased people and 5 normal people for 48 hours, with no change noticed in their biceps. 6. The results may be summarized as follows.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602704 TI - [Three cases with temporomandibular joint dysfunction syndrome in adolescents whose mandibular are asymmetrical]. AB - We encountered three patients with TMJ dysfunction syndrome in adolescents whose mandibulars were asymmetrical. In two cases, we tried to treat with EMG Biofeedback therapy in order to improve a form and function. The following results were obtained from the progress and result of the treatment. Asymmetry of mandibular causes the functional disharmony of masticatory muscle and it is probable that its asymmetry causes TMJ symptoms. These symptoms are improved with an occlusal splint, occlusal adjustment and occlusal reconstruction. The form does not change with the EMG Biofeedback therapy which is used in order to activate the masseter muscle. The function changed but was not stable. PMID- 2602705 TI - [Treatment of Riga-Fede's disease by resin-coverage of the incisal edges and seven cases of natal and neonatal teeth]. AB - This report concerned 2 cases (1-month and 8-day-old boy and 5-month and 27-day old boy) of Riga-Fede's disease. The cases were treated with photopolymerized resin coverage of the incisal edges. Generally, the treatment methods for Riga Fede's disease are discing and extraction of the traumatized teeth. The photopolymerized resin coverage proved to help in the rapid healing of the ulcerations. This method is useful because it is easy and is able to avoid a false pulp exposure of the hypoplastic natal and neonatal teeth by discing. 7 cases of natal and neonatal teeth were encountered at the Pedodontic Clinic of Niigata University Dental Hospital during 8 years from September 1979 to August 1987. 1) 7 cases were 3 boys and 4 girls, aging from 21 days after birth to 3 months 19 days. 2) Only one baby had a low birth weight. 3) The natal teeth accounted for 6 cases and the neonatal teeth accounted for 1 case. All were lower central primary incisors (5 on the right side, 1 on the left side and 1 bilateral). There were no supernumerary teeth. 4) 5 cases were of hypoplastic teeth. 5) Riga-Fede's disease was recognized in 3 cases. 6) The prognosis was 1 case of shedding, 2 cases extracted and 4 cases remaining. 7) Mesial inclination of the neighboring teeth and narrowness of the extracted space wee observed in the cases where extraction was performed at an early age. 8) Microradiogram and undemineralized specimens of the extracted tooth revealed that the tooth was very thin and mineralization was so poor and there was almost no root formation. PMID- 2602706 TI - [A case of horizontal impaction of mandibular left and right deciduous central incisors]. AB - This paper reports on a rare case of horizontal impaction of the mandibular left and right deciduous central incisors. The patient was a 4 year and 7-month-old girl at the time of first visit to our clinic. She had no previous history, and there was no family history or anomaly in her general physical condition. All the deciduous teeth except the mandibular left and right deciduous central incisors had already erupted. The right deciduous central incisor was impacted completely and the left one erupted with its incisal edge about 2 mm at the lingual gingiva. In the X-ray examination, the horizontal impaction of the mandibular left and right deciduous incisors were noted. There were no cysts, odontoma or tumors. Both of them were extracted to prevent loss of space for the permanent central incisors. Each root of both teeth was curved 90 degrees in the lingual direction at half of length of the root. There was no anomaly of figure and color in their crowns. In the histopathologic examination, there was no anomaly except for the small root resorption at the labial and lingual sides. 3 years and 3 months after extraction of the deciduous central incisors, approximately two thirds of the crowns of the left and right mandibular permanent central incisors have erupted. Both of them incline to the lingual direction and rotate and there is a space of about 5 mm between them. This case is still under observation. PMID- 2602707 TI - [Dentigerous cysts of children treated by cyst wall enucleation. Report of eleven cases]. AB - The present paper describes ten children with eleven cases of dentigerous cysts which were treated by extraction of the primary teeth, cyst wall enucleation and lingual-arch spacemaintainer. The patients were seven boys and three girls, with a mean age of nine years two months, in Hellman's Dental Age IIIA and IIIB. In eight of the cases, the mandibular second premolar was involved, and of the remainder, two cases involved the first premolar, and one case, a maxillary lateral incisor. In eight out of the eleven cases, the pulp of the primary tooth had been treated. Radiographically, nine cases exhibited a pericoronal space of 15 mm-35 mm and two cases 50 mm-55 mm. The material for histological examination, typically, gave the appearance of a stratified squamous epithelium showing chronic inflammation. Healing took place more rapidly than routine marsupialization. In eight cases the successor erupted in the normal position without orthodontic treatment, in two cases with light orthodontic power. In one case the behavior of the permanent tooth was kept under observation. From the above, this approach to treatment by cyst wall enucleation and lingual-arch spacemaintainer would appear to be very useful for the young child. PMID- 2602708 TI - [A case of Ehlers-Danlos syndrome]. AB - Ehlers-Danlos syndrome, an inherited connective tissue disorder, is characterized by skin hyperextensibility, joint hypermobility and skin fragility. The disease is at least classified into 10 types, I to X, based on clinical features, biochemical abnormalities of the connective tissue and the mode of inheritance. A case is reported of a 6-year, 8-month-old girl who showed the features of the Ehlers-Danlos syndrome type VII. The findings were as follows: 1) Soft and velvety touch skin, characteristic joint hypermobility, talipes varus, and ventricular septal defects were present. 2) Widely set eyes, slight stabismus, epicanthal folds of the eyes, antimonogoloid slanted eyes, a broad bridge to the nose and low set ears were observed. 3) Gingival bleeding following toothbrushing, Enamel hypoplasia, high arched palate and laxity of the temporomandibular joint were present. 4) In the findings of the maxillary and mandibular dental arches, there was no tendency towards conical teeth in the deciduous dentition, and the width and length of the dental arches were remarkably narrow and short. 5) The roentogenographic findings revealed that there were no minor root deformities, pulpstones and calcification of the pulp. 6) The measurement of the width, length, and depth of the palate through moire topography revealed that the palate was narrow and deep compared with the control. 7) As a result of cephalometric diagnosis, the nasion appeared to be protruded, therefore maxillary and mandibular seemed to be relatively retracted, and the gonial angle was obtuse. The dental management of patients with Ehlers Danlos syndrome was discussed and reviewed. PMID- 2602710 TI - [A treated case of facial tic caused by a psychological factor. Successful case approached by psychosomatic dentistry]. AB - As the oral psychosomatic diseases of infants appear connected with a predisposition of their environment, environmental adjustment and psychotherapy on the basis of psychosomatic dentistry are necessary in the treatment. We encountered a 9-year-old boy who seemed to be suffering from a facial tic caused by psychological factors. An attempt of therapy on the basis of psychosomatic dentistry was made in this case. The results as follows were obtained: 1. Intake interview to a mother was carried out regarding a cause of the tic. It was shown that the attitude of the mother will bring up the child and her meddling as well as the stress of school life caused his facial tic. 2. With our guidance, the mother reconsidered her meddling attitude toward the patient. And she was able to handle the patient with a kind attitude. 3. After play therapy as preparation, catharsis was carried out on the patient, the tic decreased rapidly. 4. Finally a token economy method was used. 5. It was thought that sufficient correspondence on the basis of psychosomatic dentistry was beneficial in the therapy of patient with psychosomatic disease in pedodontics. PMID- 2602709 TI - [The influence of dental health examination in primary school on caries situation]. AB - The purpose of the present epidemiological study was to clarify the influence of regular dental health examination practiced as school dental health care on the caries situation. The data analyzed were the result of dental examinations for 272 1st year pupils attending a junior high school which was attached to a private educational institution with pupils and students ranging from the kindergarten to university level. The institution is conducting regular dental health examination for all but the primary school. We analyzed the differences in the situation of caries between pupils who had graduated from the primary school which was attached to the institution and pupils from other primary schools. The former group was composed of the pupils who had not received regular dental health examination in primary school and the latter was composed of the pupils who had received it. Then, including the factor of the dental health care in kindergarten, we obtained the following results. 1) No significant difference in caries prevalence was found between the pupils who had not received regular dental health examination in primary school and the pupils who had received it, among male and female pupils respectively. 2) Both male and female pupils who had received regular dental health examination revealed a significantly higher rate of filling than pupils who had not received it. 3) Concerning pupils who had not received regular dental health examinations, the caries prevalence only among male pupils who had graduated from kindergarten attached to the institution was higher than that of the pupils from other kindergartens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602711 TI - [The state of the recall visit at the pediatric dentistry clinic of Nagasaki University Dental Hospital]. AB - The purpose of this study is to discover the actual condition and the state of the recall visit of the patients who appeared at the Pediatric Dentistry Clinic of Nagasaki University Dental Hospital, and to compare the results of 1987 and 1985. Concerning the making of appointments for the recall visit, we sent cards to patients in 1987 though, in 1985 we did not send cards to the patients so the patients themselves had to make a telephone call to arrange an appointment. The results were as follows: 1) The rate of the patients who were making their first time recall visit increased by means of sending cards to patients. 2) Of the total number of 493 patients who appeared at our clinic in 1985, 127 (25.8%) did not finish their dental treatment and stopped visiting our clinic for treatment. 3) The rate of the patients who finished their dental treatment and were making the first time recall visit was 69.9% in 1987. 4) The average ages of the patients were 6 years 5 months in 1987 and 5 years 6 months in 1985. The lower the age of patients, the higher the rate of the recall visits, while the rate of pre-school children was higher than that of school children. 5) The rate of the patients who finished their dental treatment and made recall visits was higher in cases in which the chief complaints of the first visit were caries prevention (86.2%) and caries treatment (71.3%) than the cases of tooth extraction (50%), tooth shape anomalies (50%) and tooth pain (50.5%). 6) There was no significant difference in the number of caries decayed teeth at the first oral examination between the group of patients making their first recall visit and the group of patients rejecting a recall visit. 7) In the case of the patients to whom space retainers and orthodontic appliances were applied, the rate of making recall visits decreased more in 1987 than that of 1985. 8) There was no difference in the rate of those making their first time recall visit between the two categories of diseased children and nondiseased children. PMID- 2602712 TI - [Clinical study of ectopic eruption of permanent incisors and first molars]. AB - Using the X-ray films, plastic models and pathological photograph of 4824 patients seen at the Department of Pedodontics of Iwate Medical University, the patterns of ectopic eruptions of permanent incisors and first molars (restricted to these teeth in this study) were classified into 4 groups (I-IV) to investigate the conditions of its incidence, size of the teeth and dental arch, and conditions at the stage of the mixed and permanent dentitions. RESULTS: 1. The total frequency of ectopic eruptions was 5.6%. No difference based on sex was found. 2. By classification, ectopic eruptions of the upper and lower permanent central incisors (Group I) amounted to more than half of the total frequency. The incidence of ectopic eruptions of the upper and lower permanent first molars (Group III) was very low and amounted to only 4.6% of the total frequency. 3. In Groups I and III, the incidence was higher in the maxilla than in the mandible. 4. Based on sex, the incidence was higher in boys in Group III and in girls in group II. 5. Ectopia of the permanent central incisors was frequently bilateral and those of the lower permanent lateral incisors and upper permanent first molars were frequently unilateral. 6. The mesiodistal width of the ectopically erupted permanent teeth tended to be somewhat enlarged, but showed no significant differences from Ono's mean value. 7. In ectopic eruptions at the area of the incisors, the C-C distance was narrowed with an increase in the ectopically erupted permanent teeth. 8. In patients in whom the permanent dentition was formed without occlusal guidance, the basal arch length and dental arch length were large and basal arch width and dental arch width were small. 9. In cases which were followed from the deciduous dentitions to permanent dentitions, the anterior tooth area at the stage of the mixed dentition was frequently crowded. Occlusal guidance was carried out in more than half of these cases. PMID- 2602713 TI - [Chemical change of calcium hydroxide contained in root canal filling materials in serum]. AB - In the previous report we showed the conversion of calcium hydroxide contained in root canal filling materials to calcium carbonate by means of 4 weeks of subcutaneous implantation in rats. The purpose of this study was to discover if this reaction would take place in vitro as a chemical reaction and also to find out the rate of the conversion. The alteration of three materials. Vitapex, Calvital, calcium hydroxide, when in serum, was checked and the alteration of the latter two, when in the air, was checked. The solubility of calcium hydroxide in serum or distilled water was also determined. The results showed that calcium hydroxide was neutralized to calcium carbonate after several weeks in the serum. The conversion in the air was much slower than that in the serum. This means that calcium hydroxide will not change while in storage and when it has no contact with the tissue fluid. Calcium hydroxide was dissolved in both the serum and distilled water, but calcium carbonate was not. This fact suggests that calcium hydroxide neutralized to calcium carbonate by serum will cause little or no chemical irritation. PMID- 2602714 TI - [Topesthesia and the tooth development]. AB - The present study was so designed to evaluate the change of topesthesia based on the degree of resorption of deciduous teeth and the grade of root formation of permanent teeth. A total 12315 teeth (6140 deciduous teeth and 6175 permanent teeth) from 311 boys and 364 girls, whose ages ranged from 3.9 to 17.2 years (average 8.3 years) were examined. After taking dental X-rays, 20 g of pressure was applied on the axially direction on each tooth, and then the child was requested with his index finger to identify which tooth was perceived to be pressed. A specially designed tooth pressing device was used. For reference, the measurement of the root surface was made on an extracted tooth using a digital image analyzer (MAGISCAN-IIA). The followings were the results obtained in the present study. 1) The topesthesia of the teeth was found to be more accurate in mesially located teeth than in distally located teeth. Some children falsely indicated the mesially located teeth. 2) The topesthesia of deciduous teeth was increased more as the resorption of the teeth was progressed. 3) The topesthesia of the permanent teeth decreased as the root formation developed. 4) Negative correlation was noticed between the topesthesia and amounts of the root surface remaining. (Correlation coefficient of upper jaw -0.94, lower jaw -0.89). PMID- 2602715 TI - [A longitudinal study on individual fluctuation of signs in accordance with TMJ dysfunction syndrome in adolescents]. AB - There are no reports with regard to fluctuation of signs concerning the TMJ dysfunction syndrome in adolescents. Concerning this problems, we examined 145 children (70 boys and 75 girls) of junior high school age and 429 children (202 boys and 227 girls) of senior high school age for 2-years (total 3-years) longitudinally. The results obtained were as follows: 1. The incidence of the TMJ dysfunction syndrome involved 10.3% in 1984, 15.9% in 1985, 15.9% in 1986 of junior high school age students and 11.7% in 1984, 18.4% in 1985, 31.0% in 1986 of senior high school age students. 2. The incidence of the individual that at least once during the 3-years period showed some or multiple signs of TMJ dysfunction syndrome was 31.0% of junior high school age students and 39.8% of senior high school age students. The incidence of the individual that had shown no signs of the TMJ dysfunction syndrome at all during the 3-year period was 69.0% of junior high school age students and 60.4% of senior high school age students. 3. With regard to individual fluctuation of signs of the TMJ dysfunction syndrome, there was a total of 2.8% of junior high school age students and 5.1% of senior high school age students, signs being recorded for all 3-years. In 28.3% of junior high school age students and 34.5% of senior high school age students, signs fluctuated during the entire 3 years. PMID- 2602716 TI - [A classification of foods by the amount of masticatory action involved]. AB - With a view to classifying foods on the basis of the amount of masticatory action required, an attempt was made to correlate the properties of different foods as shown by mechanical measurements with the amount of masticatory action involved as determined by means of an electromyogram. We obtained the following results: 1) We found an extremely high correlation (r = 0.924) between the amount of masticatory action involved and the mechanical properties of our samples when these were expressed as values given by the formula: log (firmness x cohesiveness x strainess x 10) We refer to this parameter as toughness. 2) We were then able to estimate the amount of activity necessary in actual mastication of various foods from out toughness values and other values obtained through texturometer readings, a procedure which we carried out for 144 types of foods. 3) We were thus able to classify foods into ten levels according to masticatory action. We further feel justified to add masticatory action to our list of classification criteria as set out in an earlier report by the present author and others entitled "A classification of foods by physical properties." PMID- 2602717 TI - [Studies on the position of the mandibular foramen]. AB - Accurate investigation of the position of the mandibular foramen is important in anatomical and clinical studies, and there are a number of reports about such measurements. In this study, 140 Indian dry skulls, whose dental stages ranged from the stage before deciduous occlusion to the later phase of third molar eruption, were reproduced and the position of the mandibular foramen was measured using laser beams and three-direction photography. The position of the mandibular foramen was defined by the tip of the lingula mandibulae. 1. The angle of the lingula mandibulae was 45 degrees in children and it decreased with ageing. 2. At the later phase of the deciduous occlusion stage, the distance from the occlusal plane to the tip of the lingula mandibulae was high. 3. Each distance increased with the increasing age, height and width of the ramus mandibulae, the front and rear of the lingula mandibulae, and height of the lingula mandibulae. 4. There was little change with age in the ratio of the height of the ramus mandibulae to the height of the lingula mandibulae, and the ratio of the width of the ramus mandibulae to the distance of rear the lingula mandibulae. 5. The method for producing anesthesia in the mandibular foramen of children is as follows. The injection is aimed at the lingula mandibulae, which is 1/2 of the height and 1/2 of the width of the ramus mandibulae, from between the deciduous canine and the first molar on the opposite side, at a 10 angle to occlusal plane and at a 45 angle to the median line. In this manner it is possible to inject into the pterygomandibular space safely and expect certain anesthesia. In this study, the position of the mandibular foramen of children was accurately determined, as well as a safe clinical method for producing anesthesia to the mandibular foramen. PMID- 2602719 TI - Urinary incontinence. PMID- 2602718 TI - [Effect of epidermal growth factor (EGF) on proliferation of the cells derived from the root resorbing tissue of human deciduous teeth]. AB - The resorption of the roots of deciduous teeth is a physiological phenomenon. Many morphological and histological investigations of the root resorption have been reported. However little biochemical data concerning systemic factors in it are available. In this study, cell culture derived from the root resorbing tissue of human deciduous teeth was tried and the effect of EGF on that cell was examined. The dissected root resorbing tissue from human deciduous teeth was cultured in a medium containing 10% fetal calf serum in a humidified incubator at an atmosphere of 5% CO2 in air at 37 degrees C. The outgrowing cells from root resorbing tissue were a mixed population of mesenchymal cells and epithelial cells during the early stage of cultivation, but at the later stage they changed to morphologically single population. The mesenchymal cells seemed to be derived from the dental sac and the epithelial cells from the enamel organ or the oral mucoepithelium. These cells seemed to be useful for analysis of the systemic factors in the root resorption. The effect of EGF on the proliferation of cells obtained as stated above was examined. EGF markedly stimulated DNA synthesis about by a factor of 6.9 for the mesenchymal cells and by a factor of 3.4 for the epithelial cells. These results suggested that EGF participates in the root resorption of human deciduous teeth. PMID- 2602720 TI - Renal cell carcinoma. PMID- 2602722 TI - Surgery of renal cell carcinoma with inferior vena caval involvement. PMID- 2602721 TI - Surveillance as a possible option for management of metastatic renal cell carcinoma. PMID- 2602723 TI - The Nordic School of Public Health in Goteborg. PMID- 2602724 TI - Autonomy and paternalistic behaviour in care. AB - The aim of the present study is to identify ethical dilemmas as experienced by hospital personnel. The dilemmas reported often focused on problems of hospitalised patients' autonomy. Tape-recorded interviews were performed with different categories of personnel, from different care areas. One of the problems was found to be a diminishing autonomy for hospitalised patients, especially in the areas of long-term and psychiatric care. According to the interviews the reasons for the obstacles for autonomy were due to the hospital organisation, the staff, the patients themselves and to relatives. PMID- 2602725 TI - Instrumental activities of daily living in two patient populations, three months and one year after a stroke. AB - The pattern of instrumental activities of daily living (I-ADL) such as household work, locomotion, psychosocial functions and intellectual activity was investigated in two groups of patients, three months and one year after a stroke. Group A (n = 78 at three months, n = 63 at one year) had received conventional care during the hospital period, while Group B (n = 129 at three months, n = 120 at one year) had taken part in a more individualised care programme. There was no difference in I-ADL performance between the two groups on the follow-up occasions according to interviews. The individualised care programme in the present study did not result in any significant differences in long-term functional improvements, although the mortality rate was somewhat lower in Group B. The patients of both groups were dependent to a large extent on somebody else in all activities except locomotion. Three-fourths of the patients, however, declared that they were satisfied with their health and life situation, in spite of their handicap. PMID- 2602726 TI - Caring paradigms. A study of the origins and the development of caring paradigms among nursing students. AB - The international discussion about caring has been reflected by two central themes in the twentieth century: (1) How can caring be developed into a holistic paradigm focused on caring and man as a human being? (2) How can a scientific basis be formed for the education, research, and practice of caring? The purpose of this study is to describe how the paradigm should be formed, developed, and integrated among nursing students during the training period. To what extent the paradigm will remain after the training period will be presented in a later article. The data collection was done by means of a questionnaire. The paradigm measuring instrument was developed in accordance with Tornebohm's paradigm factors. The research group comprised 63 graduate students. In summary we can state that the students have a paradigm already at the beginning which can be characterised as a caring paradigm. Distinct changes have taken place during the training period. The changes are highly significant (p less than 0.001) as to all factors except the capability of developing caring activities (p less than 0.05) and getting people interested in caring (p less than 0.10). PMID- 2602727 TI - The last period of life of the very old. A pilot study evaluating the psychological autopsy method. AB - In a pilot study, the Weisman psychological autopsy was tested as a method of gaining information about the last period of life of patients age 85 and older. The main purpose for using this method is to obtain knowledge about patients' thoughts, feelings and reactions towards impending death. Twelve deceased patients were selected and the staff members who had cared for those patients were interviewed. A special guide for interviewing was followed and the interviews took place on the second or third day after death. In these twelve interviews a total of 32 staff members participated. It was shown that the staff members were well informed on issues concerning the patients daily life, health condition and medical treatment. On issues such as religious belief, perception of impending death, meaning of life and fear and joy, the staff members were mostly unaware of the patients' thoughts, feelings and reactions. The conclusion is that before using the psychological autopsy method in interviewing personnel, the level of knowledge about the patients must be tested. PMID- 2602728 TI - The modified Norton scale and the nutritional state. AB - The Norton scale was devised in 1960 as an additive scale to facilitate the prediction and prevention of pressure sore development. The scale has been used both in the original version and in modified versions both in practice and as an instrument in nursing research. In a previous study the reliability had been analysed. The present investigation comprises 501 patients who were examined weekly by registered nurses with regard to the variables in a modified Norton scale and on admission with regard to the nutritional status. There are significant correlations between the variables establishing the modified Norton scale and the different criteria included in the nutritional assessment form. PMID- 2602729 TI - [Prevention of bacterial infections using ciprofloxacin in granulocytopenic patients with cancer]. AB - The optimal approach to reduce bacterial infections in granulocytopenic patients is still controversial. Recently, fluoroquinolones have been developed and real progress has been achieved in the prevention of Gram negative bacilli septicemia. This study reports our experience with ciprofloxacin and shows the excellent tolerance of ciprofloxacin by our patients as well as promising data for the reduction of Gram negative bacilli infection. However, practical modalities to prevent infection caused by Gram positive cocci remain to be defined. PMID- 2602730 TI - [Endoscopy and histology in the diagnosis of inflammatory intestinal diseases]. AB - Colonoscopy is now a routine examination in the diagnosis and the follow-up of I.B.D. The most typical aspects of endoscopic and histological lesions are described. Colonoscopy and histological study of endoscopic biopsies permit a differential diagnosis of Crohn's disease and ulcerative colitis in 90% of the cases. Certain cases remain indeterminate even after colectomy. PMID- 2602731 TI - [Esophageal cancer: principles of surgical excision]. PMID- 2602733 TI - [The anatomo-clinical forms of acute diffuse peritonitis]. PMID- 2602732 TI - [The heated humidifier (2)]. PMID- 2602734 TI - [Etiologies of peritonitis]. PMID- 2602735 TI - [Principles of critical care during acute peritonitis]. PMID- 2602736 TI - [Surgical treatment of generalized peritonitis]. PMID- 2602737 TI - [The operating room nurse and the patient with peritonitis]. PMID- 2602738 TI - [Acute peritonitis]. PMID- 2602739 TI - [Tobacco and its pathology]. PMID- 2602740 TI - [Safety and anesthesia]. PMID- 2602741 TI - [General symptomatology of diffuse acute peritonitis]. PMID- 2602742 TI - [Professionalization of the student nurse. An experience in orthopedic surgery]. PMID- 2602743 TI - [Decubitus treatment in the spinal cord injury patient. Use of an alginate dressing (Sorbsan)]. PMID- 2602744 TI - [Localized peritonitis]. PMID- 2602745 TI - [Cancer of the esophagus. Cancer of the inferior third]. PMID- 2602746 TI - [Materials of S.M.U.R. (mobile emergency medical services). The ambulance respirator]. PMID- 2602747 TI - [Thyroid surgery: operative technic]. PMID- 2602748 TI - [Postoperative course of a thyroidectomy]. PMID- 2602749 TI - [The state of brain death. Diagnosis, resuscitation, organization with a view to multi-organ procurement]. PMID- 2602750 TI - [Judicial approach to organ procurement in France]. PMID- 2602752 TI - [Bone banks--protocol for procurement and preservation. Round table discussion]. PMID- 2602751 TI - [Review of the anatomy and physiology of the thyroid gland]. PMID- 2602753 TI - [Thyroid pathology and surgery]. PMID- 2602754 TI - [Complementary studies in thyroid surgery]. PMID- 2602755 TI - [What is your diagnosis?]. PMID- 2602756 TI - [Rheumatic disorders in HIV infection (human immunodeficiency virus)]. PMID- 2602757 TI - [10 years of percutaneous disk surgery: results and developments]. AB - The percutaneous nucleotomy via discoscopy for decompression of lumbar disk prolapse is advantageous regarding segmental stability, is less invasive and can be performed in regional anesthesia. Preoperative evaluation of indication is important. Experiences with 148 patients operated 1979-1988 are reviewed. Immediate success was achieved in 70% (overall 85% favorable results). As further development the novel technique of percutaneous intercorporal spondylodesis is presented. PMID- 2602758 TI - [A case from practice (156). Phytobezoar following proximal selective vagotomy and anterior pylorectomy for perforated duodenal ulcer]. PMID- 2602759 TI - [What is your diagnosis?]. PMID- 2602760 TI - [Heart infarct--who and how will be rehabilitated?]. PMID- 2602761 TI - [Holistic medicine--away from the separation of mind and body]. AB - The purpose of liaison-psychiatry is to sensitize the colleagues for the aspect of the patient as a whole. The German expression 'wie er leibt und lebt' (as he exists in and with his body, and lives) is expressing this holistic view and says that the human being is living and experiencing himself in his corporal being and subjectivity. The body simultaneously is a somatic process and experience. If the physician wants to understand the human being, consulting him as an undivided entity, he has to be able to grasp the organ language as posture, as expression of the patient's subjectivity and of his self-esteem. He has to consider that the 'organ choice' shows, besides hereditary, culture and individual factors, the role which an organ plays within a family and an individual. The organ language can also be a significant expression of a basic drive problem. In the encounter with the patient it is further important to notice that he often is only the 'presented symptom' of the family. The vulnerability of a human being, genetically and life-historically caused, is different according to age. The cultural background out of which a human being originates decides on a more somatic or a more verbal mode of expression, whereby in our cultural background prejudices are existing against the emotional expression in the body language. In therapy, unconditional understanding may be expected of the physician.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602762 TI - [AIDS: inventor of vaccines hopes for medications]. PMID- 2602763 TI - [Acute organic psychoses in the general hospital. II. Treatment and development]. AB - This paper outlines the importance of close collaboration between the consultant psychiatrist and the non-psychiatric team. The aetiological treatment requires the competence of the physician, while the management of behavioral disturbances may require the intervention of the psychiatrist. The latter may be helpful in the choice of the right psychotropic medication and/or in counselling the team regarding the attitudes to be held towards the patient. Furthermore, the course of acute organic psychotic disorders is described. PMID- 2602764 TI - [Divine judgment in psychosomatic educational medicine]. AB - "Zeitgeist" has been since the french revolution and still is agnostic, secularized and materialistic--also in the scholastic medical sciences: Presence and action of gods supernatural forces in all nature, including disease processes and healing has not been and is not recognized. The natural sciences dominate scholastic medicine, a state to be changed in these and the following decades. The search for god's acts in diseases and therapy is growing, becomes fashionable. The scientific principle of understanding being an excellent one will be complemented in medicine with one asking for god and his intention. This principle is elaborated on under the term of "principle of Christ's science". God's reason is the authority reigning over human reasoning. This applies equally to scholastic psychosomatic medicine. Our fundamental psychosomatic therapy is reviewed. PMID- 2602766 TI - [Expert committees and their intellectual abridgements]. PMID- 2602765 TI - [Observations on science and religion]. AB - Our view of the universe used to be primed by religious terms. Our perception of the world has changed fundamentally under the influence of natural sciences. Today religion faces the difficult task to integrate scientific knowledge into its teaching. PMID- 2602767 TI - [The emergency case]. PMID- 2602768 TI - [Emergency activities of the practitioner and his legal responsibility]. PMID- 2602769 TI - Definition of polymicrobial bacteremia. PMID- 2602770 TI - Actinobacillus actinomycetemcomitans infection. PMID- 2602771 TI - Infection due to Actinobacillus actinomycetemcomitans. PMID- 2602772 TI - Gentamicin-resistant enterococci and endocarditis. PMID- 2602773 TI - Measles vaccine. PMID- 2602774 TI - Poncet's disease: tuberculous rheumatism. PMID- 2602775 TI - Pseudomonas bacteremia in a community teaching hospital, 1980-1984. AB - The epidemiologic characteristics, clinical course, and outcome of 96 episodes of pseudomonas bacteremia occurring during 1980-1984 in a community teaching hospital are reviewed. The male-to-female ratio for the patients involved was 1.9:1. The mean age was 64 years, and 41 patients were greater than or equal to 70 years of age. Sixty-two episodes were nosocomially acquired; nine were acquired in nursing homes. Twenty episodes were polymicrobial. The respiratory and genitourinary tracts were the most common sources of bacteremia. Seven patients had splenectomies prior to the onset of bacteremia. The overall mortality was 61%; mortality attributable to pseudomonas bacteremia was 48%. Statistically significant differences in mortality were related to underlying conditions and portal of entry. Findings in this series were compared with those in published series from different institutions over a period of years. Pseudomonas bacteremia remains a major infection in patients with underlying diseases and continues to cause high mortality in the 1980s. PMID- 2602776 TI - Serratia bacteremia: review of 118 cases. AB - A review was conducted of 118 episodes of serratia bacteremia in cancer patients during a 16-year period. The infection occurred most commonly in patients with acute leukemia. Most patients acquired the infection in the hospital, and 61% had received antibiotic therapy during the preceding 10 days. Fever occurred in 90% of cases and shock in 18%. Thirty-eight percent of patients had concomitant pneumonia. Patients with shock, pneumonia, or hemorrhage had a substantially poorer prognosis. The response rate was 75% for patients who received appropriate antibiotics, 22% for those who received inappropriate antibiotics, and 29% for those who received no antibiotics. Patients who continued to have positive blood culture results while receiving appropriate antibiotic therapy had a poor diagnosis. Patients who received only an aminoglycoside had the poorest response rate among those who received appropriate therapy. PMID- 2602777 TI - Clinical infections and nonsurgical treatment of parapharyngeal space infections complicating throat infection. AB - The clinical features and management of eight patients with parapharyngeal space infection who presented with swelling of the neck subsequent to sore throat are described. In four patients the interval between the initial throat symptoms and swelling was 2 days or less, and the disease was rapidly progressive with stridor or a descending mediastinitis. In the other four cases, this interval was longer (4 to 14 days) and the infection was fairly localized. Computed tomography was useful for making the diagnosis, establishing that the infection had spread into other deep neck spaces and the mediastinum, distinguishing abscesses from diffuse cellulitis, guiding drainage aspiration, and assessing the response to therapy. None of the patients underwent extensive surgical drainage of the deep neck spaces. A nonsurgical approach with antibiotics, including high doses of benzylpenicillin, and computed tomography-guided selective needle aspirations proved successful. Even patients with distinct abscesses were completely cured. PMID- 2602778 TI - Multiple hepatic abscesses caused by Streptococcus milleri in association with an intrauterine device. AB - We report a case of Streptococcus milleri bacteremia and multiple hepatic abscesses secondary to an intrauterine device and a tuboovarian abscess. Hepatic abscess as a complication of an intrauterine device has previously been reported only once, with Actinomyces israelii as the causative agent. Our patient's hepatic abscesses were cured with medical therapy. PMID- 2602779 TI - Infection in acute leukemia: an analysis of 433 episodes. AB - Two hundred fifty-seven patients with acute leukemia were admitted into our hospital on 346 occasions. There were 433 episodes of infection, with an average of 1.25 episodes per hospitalization; 126 patients (49.0%) died. Infection was the major predisposing factor and cause of death. The incidence of infection increased significantly with prolonged duration of hospitalization, the degree of granulocytopenia, the degree of chemotherapeutic failure, and the use of glucocorticoids. Pulmonary infection (17.3%) was the most common type of infection. Septicemia (12.0%) was also common and was associated with high mortality (71.2%). Of 22 patients with perirectal abscess, 10 had septicemia. Gram-negative bacilli were responsible for 66.1% of laboratory-documented bacterial infections. For the treatment of infection, empiric use of an aminoglycoside combined with either an antipseudomonal penicillin or a cephalosporin at the first sign of infection was emphasized. Antibiotic administration should be continued for at least 7 days after the patient's temperature becomes normal. PMID- 2602780 TI - Pattern of infection in hematologic malignancies: an Indian experience. AB - Ninety-nine consecutive patients who received cytotoxic therapy for acute leukemia were retrospectively studied to determine the pattern of infection at the Tata Memorial Hospital, Bombay, India. In all, 224 infective episodes occurred in these patients. Bacterial infection was the commonest type, accounting for 152 (67.9%) of 224 infective episodes, followed by fungal and viral infections (15.6% and 14.3%, respectively). Gram-negative organisms (Pseudomonas and Klebsiella) were the commonest bacterial organisms isolated, constituting 38 (76%) of 50 positive cultures; infection with Staphylococcus was rare (10%). Infective hepatitis, malaria, and systemic tuberculosis were responsible for fever with neutropenia in 20, 4, and 2 patients, respectively. Three hundred fifty-two patients with lymphoproliferative malignancies were also retrospectively studied to determine the pattern of infection. Only 53 infective episodes were recorded. In these patients, in contrast to those with acute leukemia, viral infection (33 [62.3%] of 53) and pulmonary tuberculosis (18 [34%] of 53) were frequently seen. It is interesting that 50% of our patients with hairy cell leukemia also had tuberculosis. Bacterial infection was conspicuous by its absence. Knowledge of the prevailing pattern of infection permits the development of investigative and therapeutic approaches of optimal efficacy. PMID- 2602781 TI - Tropical disease in the immunocompromised host: melioidosis and pythiosis. AB - Melioidosis is an infection of humans and animals caused by a gram-negative motile bacillus, Pseudomonas pseudomallei. Forty-nine patients with melioidosis complicating diabetes mellitus, collagen vascular disorders, leukemia/lymphoma, and other hematologic malignancies are described. Twenty-nine of these patients had disseminated/septicemic infection, two developed toxic shock syndrome, and one with AIDS experienced recrudescent melioidosis. Patients with disseminated melioidosis often have a variety of defects in cellular immunity both in vitro and in vivo. In humans with recrudescent melioidosis, cellular immunity can be transferred by a transfer factor and by levamisole, a cellular immunopotentiating agent. The results of the treatment of our patients with disseminated/septicemic melioidosis with antimicrobial agents in combination have been successful. In recent years, four cases of fungal arteritis due to Pythium species and one case of keratitis due to Pythium were seen. Almost all patients with fungal arteritis had thalassemia; all presented with pain in the lower extremities and gangrenous lesions of the toes. Pythium species, an aquatic Phycomycetes, was identified in these cases as a human pathogen on the basis of clinical features, pathologic findings, and--of greatest importance--the isolation of the etiologic fungi. These five cases with remarkably similar presentations exhibited certain similarities with and differences from cases of mucormycosis, entomophthoromycosis, and peniciliosis. PMID- 2602782 TI - [New findings on the embryogenesis of the uterus]. AB - In this study including twelve embryos, aged 4 to 8 weeks, and twenty-one fetuses between 9 and 25 weeks, and a group of five still-born fetuses between 25 and 40 weeks, the authors used conventional techniques of histological preparations and immuno-chemistry according to the BSA technique (biotin-streptavidin with peroxidase labelling), in order to demonstrate that the uterus presents a "dual embryogenesis". The endometrium with its stroma and the transition zone endometrium-myometrium have a coelomic origin. The myometrium with the common connective tissue derive from primary mesenchyma. According to the authors, the "dual embryology" of the uterus, would permit simplifying the taxonomy of the histogenesis of uterine tumors. PMID- 2602783 TI - [Application of the neodymium-Yag laser in treating adhesions]. AB - The authors conducted an experimental study on the possibilities of application of the "in touch" technique for microsurgical adhesion resection with a Neodymium Yag laser. It enables good hemostasis and is an alternative to the CO2 laser, the risk of causing vital organ lesions being reduced. PMID- 2602784 TI - [Hyperthermia during labor. Role of peridural analgesia]. AB - Over a period of 4 months, the authors have observed 414 deliveries, including 30 which presented a hyperthermia exceeding or equal to 37.8 degrees C (7.2%). 27 hyperthermias occurred under peridural analgesia. The thermogenic effect of this loco-regional anesthesia seems debatable since it occurs at an early stage, is transient and has a peripheral effect. The fever noted during labor indicates, most of the time, an infection. Peridural analgesia is advocated in most primiparous patients as well as in imperative labor inducements. Sometimes, this permits accepting a longer-lasting labor, exposing the patient to the risk of amniotic infection. PMID- 2602785 TI - [Pregnancy and work: apropos of sick leave]. AB - A study of sick leave from work during pregnancy has been performed from data collected by Social Security's consulting doctors in 1985. The proportion of sick leave of a duration of less than six months during pregnancy may be estimated to be 18.6% of all the reasons for sick leave for all women aged less than fifty years, and so represents the second highest reason for sick leave after mental diseases. A socio-professional inequality exists with regard to sick leave during pregnancy: the estimated frequency of sick leave for pregnancy is thirteen times higher in workers than in managers, and seven times higher in employees. PMID- 2602786 TI - [Characteristics of the menstrual cycles during the postpartum period without breast feeding according to the nature of the first period: ovulatory or anovulatory]. AB - The authors have analyzed the characteristics of menstrual cycles during the post partum without breastfeeding, according to the nature of the first period. 172 women gave the thermal curve from childbirth to the first period. Among them, 118, 111, 98 and 54 women gave the self-observation data concerning, respectively, the first, second, third and the fourth cycle after the first period. They have noticed more short luteal phases and delays in ovulation after an anovulatory first period than after an ovulatory first period. The hormonal studies in the post-partum without breastfeeding seem not to explain the whole of these anomalies ascertained beyond twelve post-partum weeks. Most authors admit that the gonadotropin axis returns to a normal state within the fifth post-partum week. Because of the peculiar kinetics of follicle development, the ovary could be an important component of the "remnant effect of gestation", that is to say, of the delay of return to post-partum ovulation following the gestation state. PMID- 2602787 TI - [Endometrial cancer associated with focal nodular hyperplasia of the liver. Syndrome or coincidence?]. AB - A case is reported regarding the association of endometrial cancer with focal nodular liver hyperplasia. These two types of tumors are hormone-dependent, raising the hypothesis of a common origin although there is no mention of such an association in the literature. PMID- 2602788 TI - [Oligoamnios and intrauterine growth retardation. Apropos of 2 cases]. AB - The authors report two cases of oligoamnios associated with growth retardation. They wish to demonstrate how important the monitoring of the pregnancy is, from a clinical and sonographic standpoint, in order to screen, among others, an oligoamnios, frequently associated with a fetal malformation, and prepare to receive the child in a suitable obstetric-pediatric environment. PMID- 2602789 TI - [Quaternary ammonium compounds in local vaginal therapy]. PMID- 2602790 TI - [Value of benzydamine, the first anti-inflammatory vaginal solution]. AB - This clinical study concerns thirty women with vaginal infections caused by Trichomonas and Candida, showing major inflammatory reactions and painful symptomatology: smarting, pruritus, oedema. Its aim is to measure the activity of benzydamine, the first NSAID to appear as a vaginal solution for local application in the treatment of vaginal inflammation and painful symptomatology. The product is prescribed with the etiological treatment. Benzydamine vaginal douche acts most rapidly on local discomfort, the foremost criterion of this study. From the very first application all the patients have noticed substantial relief which can only be attributed to benzydamine and allows for a better observance of the etiological treatment. Owing to its efficacy and immediate action on vaginal inflammation, benzydamine is a real therapeutic contribution to gynecology. PMID- 2602792 TI - [Cultural interpretation at the heart of the hospital]. PMID- 2602791 TI - [Exclusive interview: Michele Andre, Secretary of State for Women's Rights. Interview by Marie-Helene Manillier]. PMID- 2602793 TI - [Prevention of influenza]. PMID- 2602794 TI - [Tracheotomy]. PMID- 2602795 TI - [Born with laparoschisis]. PMID- 2602796 TI - [Community child services. Departmental Social Action Service of la Manche]. PMID- 2602797 TI - [Amyotrophic lateral sclerosis]. PMID- 2602799 TI - [Structure and function of emergency medical services]. PMID- 2602798 TI - [Endoscopic treatment of upper digestive tract hemorrhages]. PMID- 2602800 TI - [The nurse in emergency medical services and in mobile emergency units]. PMID- 2602801 TI - [Quality, I believe in it and I produce it]. PMID- 2602802 TI - [Usefulness of total dry blood samples on filter paper in the detection of antitoxoplasma antibodies]. AB - Direct Agglutination (DA) techniques, both, using dry blood samples in filter paper and serum samples, were compared with the ELISA test in order to detect antibodies against Toxoplasma gondii. The results show the validity of the dry blood samples in filter paper for detecting antitoxoplasma antibodies with a DA test. Our results would confirm their usefulness in field epidemiological surveys. PMID- 2602803 TI - [Biosafety in the laboratory]. AB - The occurrence of laboratory-acquired infections have elicited in the last ten years an intense interest in methods and procedures for the safe handling of microbiological material. The major laboratory safety problem is aerial transmission, however, protection against airborne hazards is efficiently achieved by the use of microbiological safety cabinets. Biosafety rules should be strictly followed by all members of a laboratory. Evaluation of these procedures should be effectively performed by an independent biosafety committee. The upsurge of AIDS should stimulate the adoption of safe working procedures in the laboratory. PMID- 2602804 TI - [Hematologic changes in leptospirosis]. AB - 30 cases of leptospirosis admitted to the Clinica de Doencas Infecciosas e Parasitarias do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo were studied for blood count alterations. 16 patients (53.3%) had a normal white blood cell count at the moment of admission. 12 patients (40%) presented a high white blood cell count and 2 (6.6%) had a low count. 29 patients (96.6%) had a high proportion of neutrophils and 25 patients (83.3%) presented a high number of immature forms. 24 patients had anemia. Thrombocytopenia was present in 26 patients (86.6%). The most characteristic changes found in bone marrow aspirate were the alterations of M:E ratio (myeloid-erythroid ratio) due to relative and/or absolute hyperplasia of the myeloid series, and/or relative and/or absolute hypoplasia of the erythroid series; erythropoiesis was predominantly micro-erythroblastic in many patients; mild to moderate plasmocytosis was found; and, regarding the interstitial series, increased macrophagic activity was noted. There was no direct correlation between the number of megakaryocytes and the blood platelet count, but there was a direct correlation between the bone marrow platelet production and blood platelet count. We believe that it is very difficult to have a good idea of the dynamic mechanisms that lead to medullar platelet production in the presence of platelet consumption, through a random test of the bone marrow. PMID- 2602805 TI - [Snake bites by Bothrops moojeni: correlation of the clinical picture with the snake size]. AB - During a period of 19 months (March 1986-September 1987), 22 cases of snake bites caused by Bothrops moojeni in Sao Jose do Rio Preto, Sao Paulo (South-east Brazil) were studied. The animals have their length measured and two groups were constituted: group I - 9 cases with length between 30 and 53 cm and group II - 13 cases with length between 80 and 147 cm. Our results revealed: 1. the local effects--pain and swelling--were frequently mild in group I; 2 - non-clotting blood (bed-side test) occurred in two groups, a little more frequently in group I; 3. local complications--necrosis, compartment syndrome and infection--occurred in more than a half and exclusively in group II, in spite of larger and faster antivenom therapy. We have concluded that larger Bothrops moojeni produced great increment in swelling, necrosis and infection and mild decrement in coagulation action. PMID- 2602806 TI - Active immunization against hepatitis B virus (HBV) with low-doses of plasma derived vaccine by intradermal route. AB - Schedule for vaccination against HBV infection has usually been based on three separate injections of 20 mcg of the vaccine by intramuscular route. One of the main shortcomings to its use in large scale programs has been its high cost. Ninety out of 300 health workers were submitted to three injections of 2 mcg of plasma-derived vaccine (PDV) by intradermal (ID) route on days 0, 30, and 180. Anti-HBs was detected in 74 (82.2%) after the second dose and in 80 (88.9%) after the third dose, a non-significant difference. However, levels above 10 times the cut-off were observed in 29 (32.2%) and 77 (85.5%), respectively (p less than 0.001). The results showed that a low-dose schedule is effective when used in health workers and should be tried with other risk groups. PMID- 2602807 TI - [Nursing registries. The key element in primary care]. PMID- 2602809 TI - [A hospital wholy computerized, the Hospital de Navarra]. PMID- 2602808 TI - [Urinary incontinence in the elderly patient]. PMID- 2602810 TI - [Iron deficiency in the industrialized countries. A lack in the context of abundance (II)]. PMID- 2602812 TI - [Scandal in geriatics]. PMID- 2602811 TI - [Continuing education. 42. Subject: Medicine-surgery. Topic: The patient on hemodialysis]. PMID- 2602813 TI - Let's clean up our language. PMID- 2602814 TI - Onward and upward at the bedside. PMID- 2602815 TI - Adoptive parents need our support. PMID- 2602817 TI - Patient teaching for x-ray and other diagnostics. PMID- 2602816 TI - When drug therapy causes diarrhea. PMID- 2602818 TI - The people who nurse people with AIDS. A photo essay. PMID- 2602819 TI - Why aren't more nurses using this valuable tool? PMID- 2602820 TI - Getting your patient off a ventilator. PMID- 2602821 TI - Hospital closings and employee rights. PMID- 2602823 TI - Our actions drown out our words. PMID- 2602822 TI - When your patient has an epidural catheter. PMID- 2602824 TI - No one nurses our patients but us. PMID- 2602825 TI - The family has a role even during a code. PMID- 2602826 TI - An uncommon condition that nurses can spot first. PMID- 2602827 TI - Would you know what caused these geriatric emergencies? PMID- 2602828 TI - Time won't tell if that OB patient's out of danger. PMID- 2602829 TI - Postpartum depression: assessing risk, restoring balance. PMID- 2602830 TI - Meningitis: dangers when the Dx is viral. PMID- 2602831 TI - Medical waste: it's not just garbage anymore. PMID- 2602832 TI - Nursing opportunities. The wide open world of jobs. Your guide to a successful career. PMID- 2602833 TI - Set your goals--then go hunting. PMID- 2602834 TI - Make a lasting impression on paper. PMID- 2602835 TI - When you're one-on-one with the recruiter. PMID- 2602836 TI - Step-by-step to your nursing license. PMID- 2602837 TI - Head back to the classroom to boost your career. PMID- 2602838 TI - The nursing jobs you've never thought of. PMID- 2602839 TI - Is a colleague holding your key to success? PMID- 2602841 TI - The young and the smokeless. PMID- 2602840 TI - Dealing with abusive behavior. PMID- 2602842 TI - Redefining universality. PMID- 2602843 TI - Managing your money: tax savings the RRSP way. PMID- 2602844 TI - Nurse-physician relationships. PMID- 2602845 TI - The power within. PMID- 2602846 TI - Eight ways to relieve the nurse shortage. PMID- 2602847 TI - Taking professionalism for granted. PMID- 2602848 TI - Occupational exposures and leukemia. AB - Using the data from a case-control study performed in 958 age, sex and place of residence matched pairs of adult inhabitants of Polish towns, the risk of leukemia related to work in several occupations was analyzed. The risk of myeloid leukemia was found to be increased by some 90% in electrical workers (p less than 0.10). Also in some medical occupations the risk was significantly increased though small numbers do not allow to establish valid estimates of risk, and all medical occupations, treated as a whole group, do not increase the risk. No increase of leukemia risk was found for occupations connected with agriculture. PMID- 2602849 TI - [Determination of elements hazardous to health in vegetables grown in the Siedlece district]. AB - In the years 1986-1987 the content of iron, manganese, zinc, copper, nickel, lead and cadmium was determined by the atomic absorption spectrometry method in vegetables grown by gardeners in Wegrow, Sokolow Podlaski and Siedlce. These elements were measured in cabbages, tomatoes, carrots, parsley, celery (root and leaves), red beet and potatoes. The content of lead in these vegetables was from 0.0 to 0.596 mg/kg, and that of cadmium was from 0.002 to 0.184 mg/kg (fresh mass). The level of cadmium in many samples of vegetables exceeded to limit permitted by the Polish Ministry of Health. Lead level in a sample of parsley leaves was two times above the permitted value. PMID- 2602850 TI - [Concentration of glycoalkaloids in the tuber of potatoes found in retail trade]. AB - Levels of glycoalkaloids were determined in potatoes sold in grocery shops in summer 1987 and during the period of potato storage (October 1987-April 1983). The average concentration of glycoalkaloids in 66 samples of unpeeled potatoes was 7.5 mg/100 g. In only two samples purchased on July 13th this level was slightly above 20 mg/100 g. Peeled potatoes contained glycoalkaloids in amounts several times lower than whole potatoes. The average concentration of glycoalkaloids was in peeled potatoes only 2.2 mg/100 g. PMID- 2602851 TI - [Residues of organic chlorinated pesticides in the fat of game from eastern Poland]. AB - The results are presented of the determinations of the content of organic chlorine pesticides in the perirenal fat tissue in wild animals killed in the years 1986-1987. The obtained mean values were similar to those found in our country in the 1980s. PMID- 2602852 TI - [Residues of ethephon in onions during their storage after treatment of the plants with ethrel]. AB - The residues of ethephon were determined in onions during their storage after previous treatment of onion plants with Ethrel. The onion varieties Wolska and Czerniakowska were used. The levels of these residues during 5 years of determinations ranged from 0.07 to 1.45 mcg/kg of fresh mass. The level of etefon residues was higher in onions treated with Ethrel later. No evident relationship was noted between these varieties or the concentration of Ethrel in the used range on the result of residue determination. PMID- 2602853 TI - [Presence of specific contaminants in waters of the Reda and Bolszewa rivers]. AB - During 3 years the water was studied in the Reda river and its main tributary Bolszewka (1981-1984) for determining the levels of heavy metals (manganese, lead, zinc, copper, mercury), phenols volatile with water vapour, anion detergents and fats and oils expressed as ether extract. Moreover the outflow of these contaminants was determined from the confluence of both rivers. The levels of lead, anion detergents and ether extracts in the water in the Bolszewka river were compatible with class I of water purity, while the remaining values exceeded several times those permissible for class I of water purity. Manganese and volatile phenols were present at the level of class III of purity, while zinc was even above that level. The outflow of most contaminants from the confluence of Reda and Bolszewka rivers in 1981/1982 was higher than in the following years which was due to a high outflow in that period, while in the last year a decreasing tendency was noted. PMID- 2602854 TI - [Mycotoxins in enzymatic preparations. 1. Method for the detection and determination of aflatoxins]. AB - A simple method for detection and semiquantitative determination of aflatoxins B1, B2, G1 and G2 in enzymatic preparations is described. The method is based on extraction with a mixture of acetone with water, purification of extracts with lead acetate and on a column with aluminum oxide. The concentrated extracts were analysed by means of two-direction thin-layer chromatography. The mean recovery by this method was from 57 to 78% depending on the type of aflatoxin. The detection limit by this method was about 1 mcg/kg. PMID- 2602855 TI - [A test for determining daily doses of consumption of ochratoxin A by humans in Poland]. AB - A trial was undertaken for determination of the average daily amount of ochratoxin A consumed with contaminated food by adults in Poland. Contamination of food with ochratoxin A was estimated to be 0.448 ng/g, and the mean level of this metabolite in human serum was 0.27 ng/cm3. These values showed a considerable similarity when they were analysed by simplified conversion factors of Mortensen et al. PMID- 2602856 TI - [Effect of the combined action of cadmium and ethyl alcohol or cadmium and acetaldehyde on the genesis of sister chromatid exchange in lymphocytes of human blood in vitro]. AB - The frequency of exchange of sister chromatids was studied in vitro in peripheral blood lymphocytes of three healthy donors. Mixtures: 3.1 X 10(-3) mM of cadmium sulphate and 43.4 mM of ethanol or 6.2 X 10(-3) mM of cadmium sulphate and 43.4 mM of ethanol or 6.2 X 10(-3) mM of cadmium sulphate and 43.4 mM of ethanol increased significantly the number of these exchanges in only one donor. Mixtures of 0.18 mM of acetaldehyde with cadmium sulphate in three concentrations: 1.6 X 10(-3) mM, 3.2 X 10(-3) mM and 6.2 X 10(-3) mM increased significantly the frequency of exchanges in all donors. PMID- 2602857 TI - [Effect of the combined action of sodium nitrite and fenitrothion on certain biochemical parameters in rat blood]. AB - The aim of the study was explaining of the combined action of low doses of sodium nitrite and fenitrothion on certain biochemical parameters in rat blood. The experiment was carried out on male adult Wistar rats. The animals were divided into 4 experimental groups: group I receiving 10 mg/kg of sodium nitrite, group II--2.5 mg/kg of fenitrothion (Owadofos), group III received a mixture of both these doses, group IV served as control. The preparations were given intragastrically through a tube for 90 days. After that time 2,3 diphosphoglyceric acid, vitamin E, SH groups in protein and non-protein compounds in erythrocytes, methaemoglobin and basic haematological parameters, as well as the activity of glucose-6-phosphate dehydrogenase, superoxide dismutase and choline esterase were determined. Sodium nitrite decreased the activity of glucose-6-phosphate dehydrogenase and vitamin E, with an increase of the activity of superoxide dismutase and protein SH groups and methaemoglobin level. fenitrothion caused similar changes as sodium nitrite and decreased the activity of choline esterase and the level of 2,3-diphosphoglyceric acid. No synergistic action of these compounds was noted. The level of non-protein SH groups was decreased. It seems that determination of the level of non-protein sulphohydryl groups may be one of the indicators of poisoning with sodium nitrite combined with phenitrotione. PMID- 2602859 TI - [Determination of fluorine in biological materials with ion-selective electrodes]. AB - Fluorine was determined in faeces of experimental rats and in krill meal by the method of ion-selective electrode. Concentrated hydrochloric acid was added to the prepared samples, and then acetate buffer was added to obtain pH 5.0-5.5 The results were similar to those obtained according to AOAC. The recovery of fluorine added to the samples in amounts from 0.2 to 0.8 mg as sodium fluoride was 90 to 98%. The method may be used also for determination of fluorine level in biological materials. PMID- 2602858 TI - [Presence of nitrates and nitrites in raw milk as subject to the system of milk purchasing]. AB - The content of nitrates and nitrites was determined in raw milk supplied to dairy works in the purchasing system: producer--milk collecting basin--dairy. In all, 480 milk samples were analysed. Most samples contained nitrates in amounts not exceeding 2 mg of NO3-/kg, while nitrites were present in trace amounts or were not detected at all. In comparison with milk taken immediately after milking the level of nitrates in milk in collecting basin was nearly twice as high. The source of these nitrates was probably water incompletely removed after washing and rinsing of collector containers. PMID- 2602860 TI - [Effectiveness of 2,6-dihalogenbenzoyl urea derivatives as potential inhibitors of chitin biosynthesis regarding the house fly Musca domestica L. and cockroach Blatella germanica L]. AB - The biological activity was determined of 20 compounds from the group of asymmetrically substituted urea derivatives. They were derivatives of 1-(hetero) aryl-3(2,6-dichlorobenzoyl)urea, compounds in Table 1, (1-12) which represented three groups of compounds: a) monochlorine or trifluoromethyl derivatives of benzene, b) monomethyl-substituted 2-pyridine derivatives, c) a derivative of 5 bromo-3-pyridine, and symmetrical derivates (Table 2 compounds 1-8) 2.2; 3.3; 4.4 groupings: a) N-(2,6-dichlorobenzoyl)urea derivatives, and b) N-(2-chloro-6 fluorobenzoyl)urea derivatives. The experiment was carried out on larvae and adult forms of M. domestica L. and Blatella germanica L. The tested substances were administered in food to the insects. Of the tested compounds complete inhibition of the development of flies was caused by the compound designated with the symbol AG 6. Compounds AG 13, AG 15 and AG 17 given to larvae inhibited the development of the insects by 33 to 100% acting mainly in later phases of the development (pupation). Compound AG 5 was found to be a very strong inhibitor of the development of cockroaches acting on larvae and adult females Of 800 tested larvae exposed to concentrations 0.001 to 1% none reached the adult phase. The exposed adult females formed cocoons but no larvae hatched from them. PMID- 2602861 TI - [Physiopathologic mechanisms of coma]. AB - The occurrence of coma betrays a deficiency of the ascending reticular activating system (ARAS) of the brain stem, which constitutes the neurophysiological support of wakefulness. Multiple factors, acting separately or jointly, may be responsible for coma. They include diffuse lesions or circumscribed lesions with repercussions on the ARAS metabolic and toxic factors, intracranial hypertension, cerebral oedema, epileptic activity, and so forth. Owing to the influence it exerts on the management of coma, the physiopathological approach is as necessary as the aetiological approach. PMID- 2602862 TI - [Clinical examination of the comatose patient]. AB - The clinical examination of a comatose patient may be divided into neurological ang general. The neurological examination aims at determining all that is proper to the state of coma, its complication, whatever they origin (mostly cerebral oedema and herniation) and its focal signs. As for the coma itself, one may distinguish between disorders of consciousness or perceptivity and disorders of wakefulness. Specific reactivity and reactivity to pain. This must be combined with a study of muscle tone (reactions in flexion and extension, reflexes). Reflexes of the brain stem, nowadays better known, provide for a better assessment of severity and a better evaluation of tiered suffering. Vegetative symptoms, including respiration, cardiovascular system, temperature, trophicity, sphincteral function, must be studies in all comas. The classification of comas into stages of severety and the relevant scores (Glasgow, Liege) must be known with their advantages and limitations. The general clinical evaluation, including past history and associated signs, may suggest an aetiological diagnosis and point to the necessary paraclinical explorations. PMID- 2602863 TI - [Role of imaging in the diagnosis of coma]. AB - Imaging has become one of the main methods to diagnose and monitor coma. CT is the technique of choice in the exploration of traumatic coma or spontaneous intracerebral haemorrhage, but MRI is better than CT to explore comas of ischaemic, infective, tumoral or toxic origin, as it provides earlier and more precise images. PMID- 2602864 TI - [Functional neurologic studies in the diagnosis of coma]. AB - Despite the development of medical imaging, functional exploration of the central nervous system by means of EEG and evoked potentials still plays an important role in the diagnosis and monitoring of coma. Together with clinical examination, these techniques contribute to the assessment of coma depth and inform, sometimes earlier than clinical signs, on the course of the coma. Finally, the data supplied by paraclinical explorations have a diagnostic value in cases of acute encephalitis, dysmetabolic diseases, drug poisoning or severe cerebral anoxia. PMID- 2602865 TI - [Prognosis of post-anoxic coma]. AB - The outcome of anoxic coma following cardiac arrest depends on the aetiological circumstances, on pre-existing visceral deficiencies and on the duration of inefficient circulation. Outside the extreme cases of prompt return to consciousness or early death, in many patients this course is marked by neurological sequelae of varying severity which may result in a persistent vegetative state. Initially, there is nothing that can predict the quality of survival, but within 72 hours the neurological examination usually makes it possible to foresee irreversible situations with permanent loss of consciousness. The decisional problems that ensue are discussed. PMID- 2602866 TI - [Problems of surveillance and nursing in chronic coma]. AB - Impaired consciousness after severe brain damage is coma, the next step being vegetative state with a high mortality rate. Some vegetative patients may in fact improve, although they usually stay dependent. The entire attending and rehabilitation team looks for responses to simple orders, which mean return of consciousness, and watches the patient's articular state and potential complications. It is also necessary to maintain the patient's dignity at this stage of wakefulness without awareness, and to prevent neuro-orthopaedic and cutaneous complications by positions and mobilizations, in order to provide optimal conditions for a possible physical and/or mental recovery and to reduce the degree of dependence. PMID- 2602867 TI - [Coma and cerebral death]. AB - The concept of cerebral death is universally accepted. It rests on a panel of signs which must all be present and constant, and provided this is the case no error is possible. No authentic case throwing doubt on this statement has ever been reported. It has been said that the term "coma depasse" which we chose in 1959 could lead to confusion with the different degrees of coma and for this reason, be an obstacle to organ donation. I do not consider this a satisfactory explanation. In favour of the appellation "coma depasse" are the originality of its first description and its use in the French medical language. It does not matter if "cerebral death" is preferred, both terms being synonymous. The individualization of "coma depasse" and the possibility of grafting organs with success are acquisitions separated by only a few years. They have made it possible to obtain the remarkable successes known to every one, they have given medical thinking a new dimension and placed upon doctors an increased responsibility. PMID- 2602868 TI - [Should a complementary treatment be added to surgical treatment in cancer of the esophagus? What should be the therapeutic sequence?]. PMID- 2602869 TI - [Radiosensitizers of hypoxic cells]. PMID- 2602870 TI - [Home self-monitoring of at-risk pregnancies]. PMID- 2602871 TI - [Abdominal injury. Diagnostic orientation and management]. PMID- 2602872 TI - [Pneumoconioses. Diagnosis]. PMID- 2602873 TI - [Neonatal jaundice. Physiopathology, etiology, treatment]. PMID- 2602874 TI - [What is new about the knee?]. AB - Surgery of the knee applies to the pathology of sports as well as to degenerative lesions. Surgery of the ligaments has benefited from the advances achieved in medical imaging, arthroscopy and rehabilitation. In case of gonarthrosis, prosthetic surgery has become reliable, but it is limited to sedentary subjects. Osteotomy remains very useful in ome indications. PMID- 2602875 TI - [Strategies for the use of complementary tests in menisco-ligamentous pathology of the knee]. AB - In patients with menisco-ligamentous pathology of the knee, the paraclinical examinations available to physicians and surgeons are standard radiography, arthrography, arthroscopy and magnetic resonance imaging (MRI). The use of these methods on whether the lesions are recent or chronic. Standard radiography and arthrography are sufficient to evaluate chronic lesions, arthroscopy and MRI being reserved to cases with complex laxity. For recent lesions standard radiography must systematically be performed. Arthrography is unreliable, being hampered by haemarthrosis and pain. Arthroscopy may be hazardous and can only be used in patients without peripheral lesions of the articular capsule and ligaments. MRI is sometimes useful, notably in cases with unrecognized post traumatic haemarthrosis and in children as it avoids hospitalization. In this article, the various situations encountered are analyzed and a strategy for the use of paraclinical examinations is offered. PMID- 2602876 TI - [What should be done in a meniscal lesion?]. AB - The treatment of meniscal lesions closely depends on the context in which they occur. In isolated lesions of the medial meniscus, meniscectomy under arthroscopy remains the best method. When the meniscal lesion complicates a rupture of the anterior cruciate ligament, meniscal suture associated with reconstruction of the ligament may be contemplated. In case of degeneration of the medial meniscus or lesion of the lateral meniscus, various therapeutic approaches may be envisaged. PMID- 2602877 TI - [Recent ligament lesions of the knee]. AB - In every case knee injury, it is imperative not to miss a possible lesion of the ligaments and, when such a lesion is present, to evaluate its severity. The practitioner who examines the injured knee in an emergency therefore plays a crucial role in taking a definite attitude when faced with lesions. Before any treatment is envisaged the lesion must be precisely diagnosed. This requires a very strict examination based on the patient's history and on clinical tests that are often simple. At the slightest suspicion of severe lesion of the ligaments, a specialist must be called in to complete the investigation, if necessary by testing under general anaesthesia and/or by performing an arthroscopy. PMID- 2602878 TI - [Chronic instability of the knee]. AB - During the last few years, major advances have been achieved in our understanding and treatment of chronic instability of the knee joint. The central hub (ACL and PCL) is the most important stabilizing element, and its rupture usually results in slipping knee, pain and recurrent hydrarthrosis, which are particularly frequent and severe in athletes. However, in some circumstances the loss of the anterior cruciate ligament can be compensated for by other stabilizing elements or by an excellent musculature. In patients with slipping knee, clinical, radiological and even arthroscopic examinations are necessary to decide on the treatment to be applied. This treatment depends on the importance and type of laxity, on the presence or absence of meniscal and cartilaginous lesions, on the degree of functional impairment and on the patient's life style. Several methods can be used, from rehabilitation alone to the replacement of the deficient ligament(s) by autografts or artificial ligaments. Treatment should not be stereotyped, and only specialist can determine the best method for each individual patient. PMID- 2602879 TI - [Artificial ligaments of the knee]. AB - A variety of prosthetic ligaments is available to orthopaedic surgeons, but non of these ligaments possesses the ideal qualities. They are made of polyester and tetrafluoroethylene. Their implantation must be perfect, since intolerance and rupture occur more frequently after technical errors. Generally speaking, the implants are well tolerated. The indications for this type of surgery are based on the age and requirements of the patients who must be warned that the material may break, even after a medium-term usage. However, these techniques constitute an interesting alternative to the conventional autologous arthroplasty: they are more rapidly performed and the post-operative period is less complicated. PMID- 2602880 TI - [Treatment and prevention of pneumocystosis]. PMID- 2602881 TI - [Erythropoietin and dialyzed patients]. PMID- 2602882 TI - [Carbon monoxide poisoning. Physiopathology, etiology, diagnosis, treatment principles]. PMID- 2602883 TI - [Conjugated bilirubin jaundice in adults. Diagnostic orientation and management]. PMID- 2602884 TI - [Arterial thromboses. Physiopathology, treatment]. PMID- 2602885 TI - [Secondary bone cancer. Etiology, diagnosis, treatment principles]. PMID- 2602886 TI - [Panlobular emphysema. Etiology, physiopathology, diagnosis, course and prognosis]. PMID- 2602887 TI - [Physiopathology of diarrhea]. AB - Diarrhoea is defined as the daily excretion of faecal water in increased amounts. Several mechanisms may result in diarrhoea. They are: (1) increase in fluid and ions load which may exceed the maximum capacity of intestinal reabsorption; this is the "volumogenic" diarrhoea observed in Zollinger-Ellison syndrome; (2) accelerated gastrointestinal transit, notably through the colon, as in the so called "diarrhee motrice" due to increased colonic motility; (3) osmotic diarrhoea due to ingestion of nonabsorbable solutes, as in malabsorption syndromes; (4) secretory diarrhoea with disorder of NaCl transport in the intestine as its main abnormality; this diarrhoea may be of bacterial, endocrine or other origin; (5) diarrhoea consecutive to morphological abnormalities of the small bowel and/or colon; it is often due to several of the above mechanisms, to which must be added exudation of blood, mucosities and proteins in the intestine. PMID- 2602888 TI - [Infectious diarrhea in the adult]. AB - Infectious diarrhoeas are usually divided into two types; toxinogenic and invasive. Invasive diarrhoeas are copious and responsible for dehydration which is the principal clinical sign; mucosal lesions and bacteraemia are absent. The most typical of toxinogenic diarrhoeas is cholera, but enterotoxicogenic E. coli and Aeromonas infections have similar clinical features. In invasive diarrhoeas the responsible microorganisms penetrate into the epithelial cells of the intestine, producing fever and stools that contain blood and mucus. However, some organisms causing invasive diarrhoeas secrete cytotoxins; they include Shigella spp., Salmonella spp, some strains of E. coli, Campylobacter jejuni and Yersinia spp. When diarrhoea occurs in patients under antibiotics pseudomembranous colitis due to the proliferation of Clostridium difficile must be suspected; the diagnosis is suggested by endoscopy and confirmed by bacteriology. Toxic and infectious diarrhoeas due to food are increasingly frequent; they are usually caused by Salmonella spp., but sometimes by Clostridium perfringens or Staphylococcus aureus. In patients with suspected infectious diarrhoea symptomatic treatment combined or not with intestinal antibacterial agents is immediately initiated in most cases; stool cultures are reserved to severe or protracted diarrhoeas. Specimens must be collected under the best conditions and rapidly sent to the laboratory. PMID- 2602889 TI - [Exploration of the adult patient with chronic diarrhea]. AB - This article describes the clinical approach to the aetiological diagnosis of chronic diarrhoea in adults, with a rational ranking of investigations starting with methodical questioning and careful physical examination. The purpose of the clinical stage is to find out whether the diarrhoea is truly chronic--and not the paradoxical diarrhoea so common in constipated subjects--, to evaluate its repercussions on nutrition and hydration, to try and determine its type (malabsorption or watery diarrhoea) and to elicit an obvious or probable cause. The paraclinical stage includes screening or confirmatory examinations separating watery diarrhoeas (due to colonic hypermotility or secretory of organic origin- mainly colonic, humoral or neurological--or functional origin) from malabsorption diarrhoeas; concerning the latter, the use respiratory tests with hydrogen is emphasized and conventional tests (D-xylose, assay of faecal fats and nitrogen) are mentioned. PMID- 2602890 TI - [Diarrhea and functional digestive pathology]. AB - Functional bowel disorders are the most frequent cause of chronic diarrhoea. Functional disorders may present as typical "diarrhee motrice" (colonic hypermotility) or as watery diarrhoea. The diagnosis cannot be made unless an organic cause has been ruled out. Although colonic motor abnormalities have been described in some patients, its physiopathology remains obscure. Treatment is the same as for functional bowel disorders, i.e. fibres and antidiarrhoeal drugs. PMID- 2602891 TI - [What is the status of fermentation diarrhea?]. AB - Diarrhoea "whith" bacterial fermentation is characterized by acidic liquid stools containing high amounts of organic acids. Carbohydrate malabsorption is the main cause; the mechanism of diarrhoea is an osmotic one, and colonic fermentation does reduce the diarrhoea. It is unlikely that starch malabsorption induces significant diarrhoea, whereas the consumption of high amounts of fibers is responsible for a "physiologic" diarrhoea. Colonic fermentations increase diarrhoea due to organic colitis and the "diarrhees motrices". They can be responsible for some intestinal symptoms in patients with the irritable bowel syndrome. This does not imply a "hyperfermentative" process due to a hypothetical disturbance of colonic microbial ecology. PMID- 2602892 TI - [Diarrhea in intestinal inflammatory diseases]. AB - Diarrhoea is a frequent symptom in ulcerative colitis (UC) and Crohn's disease (CD) which it often reveals. Its clinical features, course, physiopathology and treatment are different in these two diseases. UC is accompanied by an imperative, blood-stained, diurnal and often noctural diarrhoea the intensity of which fluctuates with the course of the disease, usually regressing under medical treatment but capable of becoming severe. This diarrhoea is due to several physiopathological mechanisms such as loss of colonic absorption function, exudative enteropathy and disorders of motility. Contrary to the lesions of UC, those of CD involve the whole digestive tract; they are multisegmental, ileal, colonic, ileocolonic or diffuse. Diarrhoea takes different forms depending on the site and evolutive stage of the lesions: malabsorption of bile salts and/or fatty acids in ileal lesions or after surgical resections, bacterial proliferation above stenoses, intestinal shunts due to internal fistulae, reduced absorbing area, exudative enteropathy and motor disorders in colonic lesions. In UC, treatment of the diarrhoea is that of exacerbations: systemic or topical corticosteroids or 5-aminosalicylic acid. In CD, side by side whit the maintenance treatment of the disease with anti-inflammatory drugs, the symptomatic treatments of diarrhoea play an important role and must be tailored to the responsible physiopathological mechanisms; some patients need artificial feeding. PMID- 2602893 TI - [Diarrhea after digestive surgery]. AB - Diarrhoea may develop after any surgery of the digestive tract, but its frequency and characteristics vary according to the type of operation. After gastrectomy diarrhoea is rare, moderate and often cryptic. After all but hyperselective vagotomies it is more frequent and may even be disabling and difficult to control. Diarrhoea is observed and may even be disabling and difficult to control. Diarrhoea is observed mostly after intestinal surgery, but it may have nutritional repercussion only after small bowel resections, while its functional repercussions are observed after colonic resections. Diarrhoea depends on the length rather than on the location of the intestinal segment resected, hence the importance of a reserve intestinal tissue below the resection. Thus, jejunal resections are well tolerated, even they are extensive, whereas ileal resections, even short, often result in a diarrhoea which is particularly pronounced when the ilio-coecal region and adjacent colon have been removed. Finally, the presence of an artificial anus increases the intestinal loss and creates its own specific problems. PMID- 2602894 TI - [Diarrhea caused by exocrine pancreatic insufficiency in adults]. AB - Diarrhea induced by exocrine pancreatic insufficiency in relation to chronic pancreatitis, pancreatic cancer, or partial pancreatic excision is generally moderate without modification of the nutritional status of the patient. However, when the malabsorption of lipids is severe diarrhoea with steatorrhea can lead to an important weight loss. Exocrine pancreatic insufficiency is managed with diet and pancreatic enzyme replacement. In patients with alcoholic chronic pancreatitis, abstinence from alcohol is the most important measure. The new enteric coating pancreatic extracts have a good efficacy and a better acceptability. PMID- 2602895 TI - [Current status of soft implants in cataract surgery]. PMID- 2602896 TI - [Proceedings of the first clinical pharmacology workshop at the Robert-Debre Hospital. Paris, 12 and 13 June 1989]. PMID- 2602897 TI - [Proceedings of the spring meeting of the French Language Association for the Study of Diabetes and Metabolic Diseases. Montpellier, 20-22 April 1989]. PMID- 2602898 TI - Methods used for testing toxicity of industrial chemicals and the need of their international unification. AB - The work presented here provides a demonstration of approaches in testing chemical substances in the world, comparison of various guidelines, shows differences in them with the aim to unify them as much as possible and thus to achieve their international comparability. First chapter includes a comparison of American and European approaches to Good Laboratory Practice (GLP). Some parts of American GLP seem to be specific for the USA only and thus they are not suitable for application on the international level where countries having different systems of government and various levels of their economy would have to observe them. GLP published in OECD and ECETOC guidelines seem to be most beneficial for needs of socialist countries. OECD, EEC, EPA/FIFRA, EPA/TSCA, Japan/MAFF and UK/HSC guidelines are compared in subsequent chapters and recommendations given by ECETOC and the authors of this work for unification of the guidelines are presented as well. Some parts of OECD guidelines are specified in detail there especially those which are most suitable for CMEA countries. Differences or supplements contained in CMEA recommendations are presented in the end of each chapter. Acute, subchronic and chronic toxicity tests were compared as well as carcinogenicity, combined carcinogenicity/chronic toxicity studies and reproductive toxicity tests. PMID- 2602899 TI - Effect of pirenzepine on aminopyrine uptake by isolated guinea pig parietal cells. AB - The inhibitory action of pirenzepine on acid secretion of isolated guinea pig parietal cells was investigated by the aminopyrine method. Pirenzepine markedly inhibited acid secretion of isolated parietal cells induced by carbachol in a dose-dependent manner but showed no inhibition on acid secretion stimulated by histamine. These results may suggest a direct action of pirenzepine on muscarinic receptors in parietal cells. PMID- 2602900 TI - Simultaneous measurement of gastric acid and bicarbonate secretion in man. AB - Experiments were performed to validate the computerized pH/PCO2 technique for measurement of HCO3 secretion at a physiologic pH in the human stomach. In bench side experiments the system detected 103 +/- 2% (mean +/- SE, n = 66) of boluses or infusions of NaHCO3. The standard curve was linear in the physiologic concentration range, and in the pH interval from 1.8 to 6.9 the recovery rate of added HCO3 was independent of the pH of the aspirate. In vivo the recovery rate of an exogenous NaHCO3 infusion (240 mumol/15 min) was 95 +/- 5% (n = 9), and there was no significant correlation between basal gastric pH and recovery rate. The results support that our computerized gastric perfusion method can be used for quantification of gastric bicarbonate secretion also at a physiologic acid pH. PMID- 2602901 TI - Polyamines in human gastric and esophageal cancer. AB - Total, free, and acetylated polyamine concentrations were investigated in gastric or esophageal tissue, serum, and urine of 40 patients with gastric and 16 patients with esophageal cancer, 40 patients with non-malignant gastrointestinal diseases, and 30 healthy volunteers by means of automated reversed-phase liquid chromatography. In both types of carcinoma polyamine levels were highly elevated in tissue, serum, and urine as compared with healthy controls, which supports the concept that polyamines play an important role in proliferating tissues. However, non-malignant gastrointestinal diseases partly showed similar elevations. A significant linear correlation of polyamines in both carcinomas was found for erythrocyte sedimentation rate but not for tumor stage, tumor size, localization, carcinoembryonic antigen, CA 19-9, and CA 125. It is concluded that owing to its low specificity, polyamine determination in serum and urine has no clinical relevance in the screening for gastric or esophageal carcinoma. PMID- 2602902 TI - 99mTc-labeled monoclonal anti-carcinoembryonic antigen antibody (BW 431/26). Clinical results in the detection of colorectal carcinomas and recurrences. AB - With the introduction of 99mTc-labeled monoclonal antibodies against carcinoembryonic antigen (CEA) a clinically relevant extension can be expected in the diagnosis of colorectal tumors by immunoscintigraphy (IS). This study comprises a total of 49 patients (primary colorectal tumors, occult neoplasms, and suspicious recurrences), in whom IS with 99mTc monoclonal antibody (MAb) BW 431/26 was performed. After injection of 1100 MBq 99mTc MAb BW 431/26 a whole body scan was performed in anterior and posterior projection 5 1/2 h later, and SPECT of the abdominal region was done after 6 and 24 h. In the course of primary tumor identification (n = 20) all coloscopically diagnosed and operatively verified carcinomas were confirmed and correctly localized by IS (n = 11). In three patients with positive IS and suspicious coloscopic findings surgery was refused by patients and relatives. In five cases IS was true negative and in 1 case false positive. In the diagnosis of recurrences (n = 29) IS showed an uptake in computer-tomographically and coloscopically suspicious areas in 17 cases. In 12 cases IS was rated negative (11 true-negative findings in scar and granulation tissue, 1 false-negative finding in para-aortal lymph nodes). Elevated serum CEA levels were found only in 17 of 31 patients with true-positive IS. In postoperative cancer care IS with 99mTc-labeled anti-CEA antibody plays a preeminent role in the exclusion or identification of colorectal recurrences. PMID- 2602903 TI - Serum anti-gliadin antibody profile in childhood protracted diarrhoea due to coeliac disease and other causes in a developing country. AB - Serum anti-gliadin antibody (AGA) titres were estimated by diffusion in a gel enzyme-linked immunosorbent assay in children with coeliac disease (n = 11), protracted diarrhoea of non-coeliac causes (n = 110), acute gastroenteritis (n = 20), protein energy malnutrition (n = 20), and asymptomatic, well-nourished children (n = 66). The mean IgG and IgA AGA titres were significantly higher (p less than 0.001) in children with coeliac disease than in any other groups. There was no significant difference (p greater than 0.01) in AGA titres in relation to age, nutritional status, or severity of villous injury. In patients with coeliac disease AGA titres showed a good correlation with disease activity. The specificity and sensitivity of the assay are discussed. PMID- 2602904 TI - Serum procollagen III peptide in alcoholic and other chronic liver diseases. AB - Increased levels of serum procollagen III peptide (P-III-P) have been found in patients with alcoholic hepatitis and cirrhosis. Serum P-III-P was increased (greater than 15 micrograms/l) in 38 of 44 (86%) patients with alcoholic liver cirrhosis, in 6 of 20 (30%) with fatty liver, in 1 of 13 (8%) with non-alcoholic fatty liver, and in 3 of 14 (21%) with other chronic liver diseases. Median serum P-III-P was almost three times higher in alcoholic liver cirrhosis than in alcoholic fatty liver (p less than 0.001). Serum P-III-P was increased in three of six patients with alcoholic fatty liver and periportal fibrosis. In the total material (n = 91), a statistically significant negative correlation between serum P-III-P and albumin (r = -0.71, p less than 0.001) and Normotest (r = -0.63, p less than 0.001), respectively, and a positive correlation between serum P-III-P and bilirubin (r = 0.65, p less than 0.001) were found. The serum level of P-III P had no prognostic value concerning the mortality in patients with alcoholic cirrhosis. PMID- 2602905 TI - Effect of long-term intraluminal perfusion of pentagastrin on rat small intestinal mucosa. AB - Mucosal changes occurring during long-term intraluminal perfusion of pentagastrin in the duodenum of conscious adult rats (100 micrograms/24 h/kg, 6 days) were studied. Significant increases of labelling and of mitotic indices were noted in the whole small intestine, with an enlargement of the crypt epithelial proliferative compartment. Differential kinetic variations were observed between upper and lower parts of the small intestine when labelling indices were measured in accordance with the cell position in the crypts. Kinetic variations were correlated to the increases of villous and microvillous area. Alkaline phosphatase and leucine-aminopeptidase-specific activities were significantly increased, suggesting modifications of synthesis and/or maturation of these enzymes. The ileal Paneth cell number was also significantly increased in the ileum. Pharmacologic doses of pentagastrin intraluminally perfused have a trophic effect at all levels of the small-intestinal mucosa. PMID- 2602906 TI - The effect of arachidonic acid and its metabolites on acid production in isolated human parietal cells. AB - The effect of arachidonic acid and its metabolites on the histamine-stimulated acid production in human isolated parietal cells provenient from endoscopic biopsies was examined. 14C-aminopyrine (14C-AP) accumulation in the parietal cells was used for evaluation of acid production. Histamine dose-dependently increased AP uptake. Histamine stimulation (taken as 100% at 10(-5) M) was significantly inhibited by prostaglandin (PG) E2 to 66 +/- 7% at 10(-8) M, 42 +/- 8% at 10(-6) M, and 13 +/- 10% at 10(-4) M (mean +/- SEM, n = 10). PGF2 alpha, PGD2, and PGI2 showed significant inhibitory effects only at very high concentrations (10(-5)-10(-4) M). Leukotriene (LT) B4 and LTC4 were without effect. The basal acid production (taken as 0%) was lowered significantly by 10( 6) M arachidonic acid to -20 +/- 7.4% (p less than 0.02, n = 10), and the histamine-stimulated (10(-6) M) acid production from 100% to 64 +/- 7.2% (p less than 0.001, n = 10). Aspirin (10(-3) M) increased basal (45 +/- 9.6%, p less than 0.001, n = 10) and histamine-stimulated (10(-6) M) acid production (164 +/- 16.3%, p less than 0.001). It is concluded that PGE2, the major product from arachidonic acid metabolism in the human gastric mucosa, is a significant inhibitor of the histamine-stimulated human parietal cell and may, in humans, play a role as a local physiologic inhibitor of acid secretion. PMID- 2602907 TI - Release of arachidonic acid metabolites during acute pancreatitis in pigs. AB - The pancreatic release of arachidonic acid metabolites was studied in a porcine model of acute pancreatitis. In situ isolation of the pancreatic gland enabled selective collection of pancreatic venous blood, pancreatic lymph, and ascites fluid. Three experimental groups were studied: 1) control (n = 9); 2) hemorrhagic pancreatitis induced by injection of 5% bile salt (sodium taurocholate) into the pancreatic duct (n = 10); and 3) edematous pancreatitis induced by injection of free fatty acid (FFA) into the pancreatic artery (n = 10). Determinations of cyclooxygenase metabolites were performed by radioimmunoassay; lipoxygenase metabolites (LTC4, LTD4) were measured by radioimmunoassay after purification by high-performance liquid chromatography. Prostaglandin (PG)F1 alpha, thromboxane B2, and PGF2 alpha concentrations were almost doubled in the lymph of the FFA group during pancreatitis, as were PGF1 alpha levels in pancreatic venous blood. However, concentrations of cyclooxygenase metabolites remained unchanged in the control group and in the bile salt group. Concentrations of LTC4 and LTD4 in lymph and ascites fluid of both pancreatitis groups increased from about 50 pg/ml to a mean level of 600 pg/ml at 6 h. Leukotriene concentrations in the control group were consistently below 50 pg/ml. The results of this study indicate that above all LTC4 and LTD4 are released from the organ and that these arachidonic acid metabolites may be also involved in the events following acute pancreatitis contributing to the systemic effects of the disease. PMID- 2602908 TI - Epidemiology of Crohn's disease in western Norway. Study group of Inflammatory Bowel Disease in Western Norway. AB - The incidence of Crohn's disease in western Norway was estimated in a prospective epidemiologic study during the years 1984 and 1985. The total population in the area was 807,000. Both inpatients and outpatients were included. Five hundred and fifty general practitioners and 12 hospitals participated in the study. A total of 86 patients were diagnosed, giving a mean annual incidence of 5.3 per 100,000. For patients between 15 and 19 years of age-specific incidence rate was 16.0 The M/F sex ratio was 0.9. In the same period 240 patients with ulcerative colitis were diagnosed (mean annual incidence, 14.8 per 100,000), giving a ratio of 2.8 between ulcerative colitis and Crohn's disease and an annual incidence of 20.1 per 100,000 for inflammatory bowel disease. Familial occurrence of IBD was found for 12% of the patients. PMID- 2602909 TI - Treatment of gastro-oesophageal reflux and gastric stasis: new perspectives with cisapride. Proceedings of a symposium of the 13th International Congress of Gastroenterology. Rome, 6 September 1988. PMID- 2602910 TI - Proceedings of the International Symposium on Omeprazole. Monte-Carlo, Monaco, 11 12 November 1988. PMID- 2602911 TI - A protective activity of physiological erythrophilic antibody in murine malaria infection and immunity. PMID- 2602912 TI - Lymphocyte binding to and penetration through vascular endothelium is stimulated by platelet-activating factor. AB - Lymphocytes have an important role in acute inflammatory reactions such as acute allograft rejection. Recirculating lymphocytes attach to vascular endothelium and penetrate through it into tissue parenchyma. Many recent studies have shown that different protein mediators, like gamma interferon, interleukin 1, and tumour necrosis factor enhance lymphocyte binding to and penetration through the endothelium, i.e. lymphocyte homing. We investigated the effect of platelet activating factor (PAF) in lymphocyte binding and penetration in vitro. Treatment of rat heart microvascular endothelial monolayers with PAF (10(-6)-10(-10) M) increased the lymphocyte binding up to 1.6-fold. The effect is dose- and time dependent. The PAF effect was reversible upon removal of the agonist: 60 min after removal of PAF no increase in the lymphocyte binding was detected. Pretreatment of endothelial cells, lymphocytes, or both of these cell types led to an increase in lymphocyte binding to endothelial monolayers. The effect of PAF in lymphocyte penetration through endothelium was investigated by using endothelial cell monolayers cultured on top of millipore filters. An optimal PAF dose (10(-8) M) for 10 min increased the number of lymphocytes penetrating through the endothelial cell monolayer into the filter by a factor of 3. These results suggest that PAF has no important role in lymphocyte homing, since it can activate the endothelial cells, the lymphocytes, or both cell types. PMID- 2602913 TI - Cyclosporine A prevents the generation of single positive (Lyt2+ L3T4-, Lyt2- L3T4+) mature T cells, but not single positive (Lyt2+ T3-) Immature thymocytes, in newborn mice. AB - The influence of cyclosporine A (CsA) on T-cell maturation was investigated in newborn mice. CsA treatment during the pre- and postnatal periods resulted in a hypoplasia of peripheral lymphatic organs, and absence of mature T3+ T cells in lymph nodes and spleens; no functional T-cell reactivity was observed. In thymuses of CsA-treated mice, no T3+ single positive Lyt2+ or T3+L3T4+ thymocytes could be found, but double positive (DP) cells were readily detected. A thymocyte subset with the phenotype Lyt2+L3T4-T3- was still discernible; this population was non-functional in vitro. The data show that the maturation of single positive (SP) T cells is critically influenced by CsA; under the conditions used here we found no evidence that 'leaky' autoreactive SP T cells develop in CsA-treated newborn mice. PMID- 2602914 TI - Rheumatoid synovial fluid reconstitutes the B-cell defect in CBA/N mice. AB - Synovial fluid from patients with rheumatoid arthritis (RA-SF) contains a biological activity which can replace T cells for activation of antibody secretion in human blood lymphoid cells and which can also induce the selective differentiation of IgG2b-secreting cells in lipopolysaccharide (LPS)-pre activated mouse spleen cells. The B-cell activity of this factor was studied in CBA/N mice which have an X-linked B-cell immunodeficiency which manifests itself as a defective humoral response to certain thymus-independent antigens (TI-2). RA SF has now been shown to reconstitute partly the B-cell deficiency in CBA/N splenic B cells in vitro. Addition of RA-SF to LPS-pretreated cell cultures results in IgG2b secretion in CBA/N spleen cells as well. In contrast to cells from normal CBA mice, cells from CBA/N mice cannot respond to interleukin 4 (IL 4) after addition of LPS with production of IgG1 antibodies in vitro. However, the addition of RA-SF completely restores a normal IL-4-induced IgG1 response. No other biologically active factors have been shown to allow the production of IgG antibody producing cells in CBA/N splenic B cells. It is postulated that the xid immunodeficiency could be the result of a deficient production of a biological activity which is abundant in RA-SF. PMID- 2602915 TI - [Ultrastructure of the epidermis in laboratory rats under normal conditions and after percutaneous administration of an organophosphate]. AB - For the study of the normal epidermal layers of the stratum basale, stratum spinosum, stratum granulosum and (male rats at the age of 2 years) were used. Skin samples were obtained from the spinal area and processed by the method of transmission electron microscopy to get semithin and ultrathin sections. An electron microscopical examination preceded by an evaluation of the semithin sections in the light microscope showed that the epidermis of both age groups contained keratinocytes and Langerhans cells. Keratinocytes are typically arranged in epidermis layers of the stratum basale, stratum spinosum, stratum granulosum and stratum corneum. These layers are of different ultrastructure. The Langerhans cells are localized suprabasally in the epithelium. In the course of keratinization, prominent ultrastructural changes in keratinocytes occur. The cell organelles of keratinocytes including the nucleus disappear and the formation of specific cell components--prominent bundles of tonofilaments, keratohyalin granules and keratinosomes--can be observed. Keratinized cells of the stratum corneum exhibit a homogeneous or fibrillar inner structure. Langerhans cells contain characteristic cytoplasmic organelles--Langerhans granules. The epidermis of old rats differs from that of young animals in a special arrangement of the dermo-epidermal junction. The most typical change (in comparison with the epidermis of young rats) is the presence of multiplied lamina densa. The qualitative study of the normal epidermis of the laboratory rat is completed by morphometric analysis. The measurements concern keratinocytes of the stratum basale. Cell dimensions under the light microscope as well as some cell organelles in ultrathin sections are evaluated. Another part of the study is aimed to estimate morphological changes in the epidermis of rats which were percutaneously administered a toxic organophosphate. In this experiment, the tissue processing for electron microscopy could be realized only when the exposed epidermal area had been previously decontaminated. A group of intoxicated animals was therefore compared with a control group, the epidermis of which was affected by the decontaminating agent only. The ultrastructural changes noted in the epidermis of intoxicated animals show no specificity. Damaged membrane organelles and vacuoles in keratinocytes, dense cells, dilated epidermal intercellular spaces containing the material of medium density, etc. are present. Furthermore, the above-mentioned changes proved to be manifestation of a combined effect of the proper toxic substance and the decontaminating agent. PMID- 2602916 TI - Theoretical and empirical problems in the assessment of alternative medical technologies. AB - Critical situations help to clarify and define otherwise indistinct and vague phenomena. The paradigm-collision which occurs when assessing alternative medical phenomena against the background of a medical school paradigm is analogous to a critical situation. An analysis of the conditions for such an appraisal has helped to highlight aspects which are not normally ascribed any great significance in the assessment of technology. It turns out that theoretical requirements, the specific concept and certain irrational elements play a large role in the assessment of medical and alternative medical technology. One conclusion is that in the appraisal of e.g. alternative medical technology, one must take into account these conditions for forming a judgement, as a basic requirement for an objective appraisal of the technology in question. PMID- 2602917 TI - The 'health-related selection effect' on occupational morbidity rates. AB - The aim of this study was to investigate the extent to which differences between physically light and heavy work, with respect to the development of health problems, might in cross-sectional data be eliminated or diminished by health related selection into and out of occupations. The study population comprised 12,314 men and 12,393 women between 25 and 74 years of age, who were interviewed within the framework of the Statistics Sweden Survey of Living Conditions. For all respondents, detailed occupational histories were recorded. For all the diseases and functional disorders studied, morbidity differences were apparently diminished compared to what would be expected if there was no selection. This association was most apparent when studying musculoskeletal disorders, impaired hearing and impaired working capacity for men. PMID- 2602918 TI - Respiratory symptoms in Danish welders. AB - In order to study the effect of welding fumes on respiratory symptoms a cross sectional study was performed in 1982 among 2,660 welders, primarily shipyard welders, compared with a control group of 881 electricians. Only workers more than 34 years of age and in work at the time of the study were selected. Information about respiratory symptoms (using standardized BMRC questions) and exposure was obtained through a self-administered questionnaire. Seventy-four never-smoking welders and 31 never-smoking controls were selected for detailed clinical interviews and extended lung function tests. This article presents the results of the questionnaire study. The welders showed a significantly higher prevalence of chronic bronchitis: 21% versus 9% in the control group (p less than 0.01). The difference could neither be explained by differences in age or smoking habits nor by exposure to other air polluting substances. Other symptoms from the lower and upper respiratory system were also significantly increased among the welders. A dose-response relationship was found between exposure to welding fumes and the prevalence of symptoms from both the upper and lower respiratory system. PMID- 2602919 TI - Changing smoking, drinking, and eating behaviour among pregnant women in Denmark. Evaluation of a health campaign in a local region. AB - Health behaviour during pregnancy was examined before and after a comprehensive health campaign targeted at pregnant women in Odense, Denmark. Furthermore, lifestyle habits were compared before and during the campaign with similar habits in Aalborg, Denmark. All 13,815 pregnant women (equal numbers from each city) were enrolled in the study, and 11,980 gave information on eating, drinking, and smoking habits during pregnancy. Data collection in both cities took place from April 1984 to April 1987. The campaign, which was entitled "Healthy Habits for Two", ran from April 1985 to April 1987 in the city of Odense only. No significant change in health behaviour in the Odense area was noted after the start of the campaign. PMID- 2602920 TI - Attitudes towards HIV infection and sexual risk behaviour. A survey among Danish men 16-55 years of age. AB - To describe attitudes towards HIV infection in relation to sexual risk behaviour and sociodemographic factors in a representative sample of Danish men 16-55 years of age, a self-administered anonymous questionnaire was distributed in connection with a personal health interview and returned by prepaid mail. The response rate was 55%, corresponding to 1,155 participants. In contrast to the official AIDS prevention strategy, 28% of the participants stated that HIV infected persons should be forbidden to have sexual relationships, and 44% that they should be registered by the authorities. 33% of the participants had had sexual behaviour which may be associated with increased risk of HIV infection: more than one female partner during the previous 12 months, sexual contact with prostitutes or sex with other men. Despite good basic knowledge of AIDS, only 41-59% of these men perceived themselves at risk, and only 47%-54% of men perceiving themselves at risk had adopted risk-reducing sexual behaviour. The results indicate a need for innovative health education of the general public about AIDS prevention at community and individual level. In the absence of effective treatment and without prospect of a vaccine in the near future the prevention of AIDS must focus on modifying behaviour associated with increased risk of HIV infection, in particular sexual behaviour. PMID- 2602921 TI - Age and injury severity. AB - This study aims at showing if and to what extent injury severity in frontal car crashes increases with the age of front seat occupants. Data on 2658 belted drivers and front seat passengers in Volvo private car series 140, 240 and 740/760, involved in frontal crashes were extracted from the Volvo Car Crash Register. The results show that the risk of injury resulting in "medical observation" does not increase systematically with age. However, the risk of fracture with any localization is more than three times higher among those aged 65-74 than in those aged 18-24, and the risk of fracture in the rib cage is nearly eleven times higher among the older than in the younger age group. It can be concluded that the incidence of specific types of injuries - as exemplified with fractures of any localization and fractures in the rib cage - increases with advancing age. PMID- 2602922 TI - Health care utilization after referral from a hospital emergency department. AB - In a trial, patients who came to a hospital Emergency Department (ED) with non urgent complaints were advised and referred to primary health care outside the hospital. The effect of this was assessed by measuring health care utilization one year before and one year after the referral, using the Stockholm County computerized medical information system and ED medical records. The proportion of the 189 referred patients who visited the ED decreased from 48% to 42%, whereas in a control group of 107 patients the proportion increased from 41% to 51%. A small proportion, 7%, of the referred patients with four or more ED visits accounted for 45% of the total number of ED visits the year before the trial. These frequent ED users did not reduce their ED utilization more than frequent ED users in the control group. The use of health care centres increased in the referred group and was practically unchanged in the control group. However, those referred patients who continued to use the ED still quite often did so for non urgent complaints. PMID- 2602923 TI - [The activity of lipase (triacylglycerine acylhydrolase, EC.3.1.1.3) in mammalian and avian organs]. AB - By means of a kinetic UV-assay, lipase activity was determined in various organs of the fowl as well as laboratory, domestic and zoo animals and the resulting tissue distribution patterns were established for the respective species. For the validation of the assay, lipase contained in canine pancreatic extracts was inhibited by tetrahydrolipostatin, a selective inhibitor of pancreatic lipase. In all examined species, the pancreas proved to be the organ with the highest lipase activity. Apart from considerable individual variation with regard to the pancreatic content of lipase, important species differences were observed and the possible causes of these findings are discussed. PMID- 2602924 TI - Clinical study on the effect of biotin on skin conditions in dogs. AB - In a collaborative study with small-animal veterinary surgeons, dogs with fur and skin conditions were treated with biotin (approximately 5 mg biotin/10 kg body weight/day) for 3 to 5 weeks. In total 119 cases could be treated which were reported to show symptoms such as dull coat, brittle hair, loss of hair, scaly skin, pruritus or dermatitis. Cases requiring other treatments with e.g. glucocorticoids, were excluded from the study. In 60% of the cases all symptoms were reported to be cured after the biotin treatment and in a further 31% an improvement was noted; in only 9% no effect was recorded. All breeds responded but to a variable extent: e.g. in Poodles the response was lower (no response in 6 out of 11 cases) than in Alsatians where all improved and 14 out of 29 were completely cured. The results confirm the favourable effect of biotin for treatment of fur and skin conditions in dogs. PMID- 2602925 TI - [Emergency treatment of limb fractures in large and small ruminants]. AB - Limb fractures in cattle have to be treated as emergencies. The success or failure of treatment depends on a careful examination and adequate emergency treatment by the veterinarian. The most important rules in an emergency treatment are the evaluation of the general systemic conditions and the initiation of whatever supportive care is required. Further attention should be paid to thoroughly rinsing and disinfecting open wounds and to immobilizing fractures for transport purposes. In 39 cases the localisation and the type of fracture were determined and the clinical relevance of a careful examination and emergency treatment was evaluated. Metacarpal fractures were the most common type of fracture. Open fractures were more likely to occur in cases of insufficient immobilisation than with properly attended patients (p less than 0,01). Open fractures have a poorer prognosis than closed fractures (p less than 0.002). PMID- 2602926 TI - Communication in medical practice. PMID- 2602927 TI - Practice location factors influencing South Dakota School of Medicine graduates (1977-85). AB - Physician numbers and placement continue to be major health delivery concerns in the rural state of South Dakota. This study of four-year graduates (1977-1985) of the South Dakota School of Medicine looks at current factors affecting physician placement and compares placement and location selection factors to a previous study of graduates of the medical school when it was a two-year program (1969 1973). Factors influencing physicians locating in South Dakota were: closeness to their home town and or spouses' home town, residency training in small towns, payment of educational loans, medical school clerkships, time of decision, etc. Factors influencing physicians locating in rural communities (less than 5,000) were: growing up in small communities, residency training in small communities, early location decisions, payment of loans, and high medical need. PMID- 2602928 TI - Cryptosporidiosis: a pathogen more common than appreciated. AB - Cryptosporidiosis is caused by a protozoan species which can produce an enteritis in humans. Until recently it was thought to primarily infect immunocompromised individuals but is now known to affect immunologically intact persons as well. It is capable of causing a severe diarrhea in small children. Discovery that the organism takes an acid-fast stain has aided greatly in its recognition in the clinical laboratory. There is no effective antimicrobial treatment, thus recognition and careful infection control practices become very important. The authors report stool studies of 247 pediatric age individuals in the Sioux Falls, South Dakota area over a four-month period. Three positive cultures for salmonella were found (1.4%) and four instances of cryptosporidium were identified (1.6%). This is similar to other reports and indicates that this organism is now one of the more frequent non-viral causes of diarrhea in children. It tends to be more common in rural areas. PMID- 2602929 TI - The chromium paradox in modern life. Papers presented at a symposium sponsored by the Association of Government Toxicologists. Bethesda, MD, 23-24 May 1988. PMID- 2602930 TI - Carcinogenic risk assessment criteria associated with inhalation of airborne particulates containing chromium (VI/III). AB - Contaminated land sites and unused chromate production facilities raise the possibility that remediation operations could involve generation of airborne particles of respirable size containing both Cr(VI) and Cr(III) in soluble and insoluble forms. These airborne particles reaching human populations in the neighborhoods involved, can pose carcinogenic risks via Cr(VI)-containing material retained in the lungs. It is proposed that the risk assessment process for this inhalation exposure be governed by the following considerations. (i) Only the respirable fraction (0.2-10.0 microns diameters) of the inhaled particulates should be considered as contributing to delivered dosage of Cr(VI) to the lung. (ii) In accordance with the ICRP analysis of particulate retention in the lung for extended intervals, the airborne respirable particle intake should be multiplied by the factor 0.125 to generate an estimate of dosage of particles retained in the lung for extended intervals, leading to possible carcinogenesis from the Cr(VI) content. And (iii), the inhalation carcinogenic risk for Cr(VI) should only be modelled in increments above a daily total chromium intake of 100 micrograms per day, a current estimate of the required daily intake of this essential mineral. PMID- 2602931 TI - Molecular basis of hexavalent chromium carcinogenicity: effect on gene expression. AB - The carcinogenicity of chromium(VI) compounds is explained in terms of the "uptake-reduction" model. According to this model, chromium (VI) enters cells as the anionic tetrahedral species chromate, CrO4(2-), using normal cellular anion transport systems, such as the sulfate transport system. Redox-active enzymes and small molecules reduce chromium (VI) intracellularly and produce "reactive intermediates" capable of damaging cellular constituents. DNA is presumed to be a critical target within the cell; however, chromium (VI) itself is unreactive toward DNA under physiological conditions in vitro. Thus, the ability of chromium(VI) to damage DNA depends on the presence of cellular components capable of producing putative DNA-damaging agents, such as chromium(VI) thioester, chromium(V), chromium(IV), chromium(III), thiyl radical and hydroxyl radical, upon reaction with the chromium(VI). The exact nature of the DNA damage will be strongly dependent on the reactive intermediates produced by cellular components and systems active in chromium(VI) metabolism. The chromium(VI)-induced DNA damage disrupts the normal functioning of DNA in critical cellular processes, including transcription and replication. The effect of chromium(VI)-induced DNA damage on the function of DNA as a template for transcription has been examined in chick embryo liver in vivo. Chromium(VI) induced DNA-protein and DNA interstrand cross-links and suppressed the induction of 5-aminolevulinic acid synthase and cytochrome P-450 mRNA by porphyrinogenic drugs. In contrast, chromium(VI) increased the basal steady-state mRNA levels of these two inducible genes, but had no effect on the steady-state mRNA levels of the constitutive genes, beta-actin, conalbumin and albumin. Nuclear "run-off" transcription experiments showed that the effect of chromium(VI) on the steady-state levels of basal and drug-inducible 5-aminolevulinic acid synthase mRNA was principally the result of changes in the transcription rate of the 5-aminolevulinic acid synthase gene. Chromium(VI)-induced changes in gene expression correlated with the presence of DNA interstrand and DNA-protein cross-links, suggesting that chromium(VI)-induced DNA lesions lead to changes in expression of the targeted genes. PMID- 2602932 TI - Environmental chemistry of chromium. AB - The processes that control the environmental chemistry of chromium include redox transformation, precipitation/dissolution, and adsorption/desorption reactions. Commonly occurring reductants, such as ferrous iron and organic material, can transform Cr(VI) to Cr(III), but manganese oxides are the only inorganic oxidants found in the environment that cause the rapid oxidation of Cr(III) to Cr(VI). In the trivalent state, chromium readily forms compounds such as Cr(OH)3 and (Cr,Fe)(OH)3. These solids show amphoteric solubility behavior, with hydroxo complexes being the dominant aqueous species of Cr(III). The relatively low solubilities of Cr(OH)3 and (Cr,Fe)(OH)3 limit Cr(III) concentrations to less than the drinking water limit over much of the pH range of environmental interest. In the hexavalent state, the formation of the Ba(S,Cr)O4 solid solution controls the dissolved chromium concentrations in environments that contain BaSO4. In the absence of solubility-controlling Cr(VI) solids, Cr(VI) concentrations in acidic to slightly alkaline conditions are expected to be limited by adsorption. Iron oxides are the most important absorbents for aqueous Cr(VI) species in most soil environments. Although these processes are complex and interrelated, each must be considered to predict the aqueous concentrations, mobility, and toxicity of chromium in the environment. PMID- 2602934 TI - Chromium and regulation: bits and pieces. PMID- 2602933 TI - Chromium carcinogenicity: California strategies. AB - Hexavalent chromium was identified by California as a toxic air contaminant (TAC) in January 1986. The California Department of Health Services (CDHS) concurred with the findings of the International Agency for Research on Cancer that there is sufficient evidence to demonstrate the carcinogenicity of chromium in both animals and humans. CDHS did not find any compelling evidence demonstrating the existence of a threshold with respect to chromium carcinogenesis. Experimental data was judged inadequate to assess potential human reproductive risks from ambient exposures. Other health effects were not expected to occur at ambient levels. The theoretically increased lifetime carcinogenic risk from a continuous lifetime exposure to hexavalent chromium fell within the range 12-146 cancer cases per nanogram hexavalent chromium per cubic meter of air per million people exposed, depending on the potency estimate used. The primary sources found to contribute significantly to the risk of exposure were chrome platers, chromic acid anodizing facilities and cooling towers utilizing hexavalent chromium as a corrosion inhibitor. Evaluation of genotoxicity data, animal studies and epidemiological studies indicates that further consideration should be given to the potential carcinogenicity of hexavalent chromium via the oral route. PMID- 2602935 TI - Kinetics of chromium transformations in the environment. AB - Kinetics of chromium transformations under typical environmental conditions were systematically investigated using batch, microcosm and column experiments. Oxidation and reduction rates were evaluated in single phase water systems and in two phase water-solid systems. Natural and reference waters, sediments and soils representing a broad range of characteristics were used. Some of the investigated reactions, such as the reduction of Cr(VI) by S2- or Fe2+ ions under anaerobic conditions, were instantaneous and the experimental results exactly followed the stoichiometric and equilibrium calculations. Other reactions, such as the reduction of Cr(VI) by organics in sediments and soils, or the oxidation of Cr(III) by MnO2, were much slower and clearly exhibited kinetic controls. Reduction of Cr(VI) by organics was dependent on both the type and amount of organic material. Dissolved oxygen by itself did not induce measurable oxidation of Cr(III), spiked to the experimental waters, after 128 days. Slow Cr(III) oxidation to Cr(VI) was only noted in one of the natural waters and sediments with half-lives ranging from 2 to 9 years. In all cases the extent of Cr(III) oxidation did not exceed 15% of the initial Cr(III) present. The overall results indicate that the transport and transformation of chromium can be predicted using kinetics data derived from a simplified laboratory experiment, the Eh-pH data and the aquatic system characteristics. Results of the microcosm and laboratory experiments were in good agreement with the predicted concentrations. PMID- 2602936 TI - Development of the revised drinking water standard for chromium. AB - Comprehensive regulations are being developed to limit human exposure to contamination in drinking water by the United States Environmental Protection Agency (EPA) under the authority of the Safe Drinking Water Act (SDWA). These regulations are being developed in several phases and include synthetic organic chemicals, inorganic chemicals, microbiological contaminants and radionuclides. This paper addresses the fundamental concepts and approaches used by EPA in setting drinking water regulations and how EPA is using these concepts to revise the drinking water standard for chromium. PMID- 2602937 TI - Inorganic chemistry of chromium and its speciation in Whetlerite. AB - Chromium compounds are among the impregnants that enhance the ability of carbon air filters to absorb and destroy toxic agents such as CK and AC. The possibility of inhaling chromium-containing carbon dust from such filters has caused concern because, in addition to being an essential nutrient, chromium has been identified as a chemical carcinogen in humans. The essentiality or carcinogenicity of chromium depends upon its chemical speciation. Solubility and oxidation state are particularly important factors in assessing the potential hazards associated with the possible inhalation of chromium-containing dusts from these impregnated carbons or Whetlerites. The chemical speciation of the chromium in Whetlerite was found to be: from 0.6 to 1.3% insoluble trivalent chromium; from 1.0 to 1.3% insoluble hexavalent chromium; and from 0.7 to 0.9% soluble hexavalent chromium. The impregnation process, and the resulting speciation of chromium in Whetlerite, is consistent with the inorganic chemistry of chromium. PMID- 2602938 TI - Speciation, bioavailability, and systemic distribution of chromium from Whetlerite dust. AB - Exploratory studies were conducted to determine if chromium from Whetlerite dust is bioavailable when administered intratracheally to rats, and if so, to determine its speciation. These studies indicated that chromium in this form and by this route of administration was bioavailable and was found in the trivalent state only. Less than 25% of the administered dose was recovered after 4 h, suggesting that most of the chromium was rapidly absorbed, distributed, and eliminated. Most of the chromium was found in the lungs and kidneys. The time course in the kidney suggests that this organ may be involved in the metabolism and elimination of trivalent chromium. Unexpected mortality in the experimental group of rats may have been due to the copper content of the Whetlerite, which exceeded the LD50 in the dose administered. PMID- 2602939 TI - Analytical chemistry of chromium. AB - The determination of chromium in most biological materials is extremely difficult because of the very low levels present. Easily accessible samples, for example biological fluids such as serum, urine, etc., usually have chromium concentrations well below 1 ng g-1. The only widely available analytical method with sufficient sensitivity is graphite furnace atomic absorption spectrometry (GFAAS), yet values reported in the early literature were wildly divergent. Man appeared to be excreting several times the amount of chromium he was absorbing from his diet. This dilemma was resolved in 1978 when it was shown that all previous chromium analytical results were probably wrong (too high), due to limitations of the instrumentation used up until then. Subsequent instruments with improved background correction capabilities have removed this limitation. However, making determinations at the sub-parts-per-billion level remains a formidable task in terms of contamination control. PMID- 2602940 TI - Nutritional chemistry of chromium. AB - There has been considerable progress in understanding the role of chromium in human nutrition. However, the lack of data on the forms of chromium-absorption from foods by the gastro-intestinal tract, and our concomitant inability to obtain an accurate assessment of the daily mobile pool of metabolically active chromium in the human body continues to be an impediment in assessing the overall impact of chromium nutrition. Based on recent chromium data on human tissues and body fluids available in the literature, an assessment of chromium content in different body compartments as well as in the total body is presented. However, on the analytical side, a few problems still persist and, therefore, a reliable analysis for chromium is restricted to a few selected laboratories. PMID- 2602941 TI - Essentiality of chromium in humans. AB - Chromium is an essential nutrient required for normal sugar and fat metabolism. Insufficient dietary chromium is associated with maturity-onset diabetes and/or cardiovascular diseases. Dietary chromium intake in the U.S. and other developed countries is roughly half of the minimum suggested intake of 50 micrograms. Well controlled studies involving human subjects have demonstrated beneficial effects of supplemental chromium on fasting glucose, glucose tolerance, blood lipids, insulin binding, and hypoglycemic blood glucose values and symptoms. Since chromium is a nutrient and not a therapeutic agent, it will only benefit those people whose signs and symptoms are due to marginal or overt chromium deficiency. Stresses including high sugar diets, strenuous exercise, physical trauma, infection and certain diseases exacerbate the signs and symptoms associated with marginal intakes of dietary chromium. While excessive levels of chromium are usually limited to industrial settings, marginal dietary chromium intake is widespread in the general population and may lead to serious health problems. PMID- 2602942 TI - Inhalation toxicity of chromium dioxide dust to rats after two years exposure. AB - Rats were exposed by inhalation to chromium dioxide (CrO2) dust at design concentrations of 0, 0.5 (stabilized and unstabilized, respectively) or 25 mg m-3 (stabilized) for 6 h day-1, 5 days week-1 for 2 years. No dust-exposure-related pathological changes were observed, other than lung lesions, in all exposed rats. There were no significant differences in pulmonary response between unstabilized and stabilized CrO2 at the 0.5 mg m-3 exposure level. The lungs showed minute dust deposition in the alveoli adjacent to the alveolar ducts, but maintained an intact general architecture. The pulmonary responses satisfied the biological criteria for a nuisance dust. At 25 mg m-3, dust deposition was sharply confined to the alveoli in the alveolar duct region. Alveolar walls enclosing dust-laden macrophage (dust cell) aggregates were thickened with hyperplastic Type II pneumocytes and slightly collagenized fibrosis. Alveoli adjacent to the terminal bronchioles were lined with bronchiolar epithelium (alveolar bronchiolarization). In addition, lungs showed foamy macrophage response, cholesterol granulomas, alveolar proteinosis, and minute fibrotic pleurisy. These pulmonary lesions occurred predominantly in female rats. Of 108 female rats, six developed keratin cysts and two had cystic keratinizing squamous cell carcinoma (CKSCC). None of 106 male rats had either a keratin cyst or a CKSCC. The lung tumors developed from metaplastic squamous cells in the areas of alveolar bronchiolarization in the alveolar duct region. The lung tumors were well differentiated and devoid of characteristics of true malignancy. The CKSCC is an experimentally-induced, unique tumor type and is different from the type of spontaneous lung tumor seen in man or animals. The relevance to man of ths type of lung tumor appears to be negligible. PMID- 2602943 TI - [Influence of microinjection of bicuculline into ventrolateral medulla on the suppression of cardiac function induced by diazepam in rabbits]. AB - Experiments were carried out on 48 rabbits anaesthetized with urethane (1 g/kg). The animals were immobilized with gallamine triethiodide and ventilated artificially. Both intravenous injection of diazepam (0.5 mg/kg) and intracerebroventricular injection of flurazepam (2 mg in 50 microliters) or gamma aminobutyric acid (GABA) (300 micrograms in 50 microliters) decreased the peak value of left ventricular pressure area of cardiac force loop and dp/dtmax. These suppressive effects of diazepam and flurazepam were prevented by intracerebroventricular injection of picrotoxin (15 micrograms in 50 microliters) or microinjection of bicuculline (3 micrograms in 0.5 microliter) into bilateral rostral ventrolateral medulla (gamma VLM). The results suggest that the inhibitory effects of diazepam on cardiac function may be mediated by activation of GABA receptor in gamma VLM. PMID- 2602944 TI - [Comparative study on the reflex responses of carotid and aortic baroreceptors in the rabbit]. AB - In 81 anesthetized rabbits, the baroreflex control of heart rate (HR), hind-limb vascular resistance (HVR) and renal sympathetic nerve activity (RSNA) was observed during arterial baroreceptor loading and unloading by intravenously injecting phenylephrine (PE) and nitroprusside (NP). The results were as follows: (1) An increase of arterial pressure with PE caused reduction in HR, HVR and RSNA, while a decrease of arterial pressure with NP evoked opposite responses. These reflex responses were reproducible. (2) By either carotid baroreceptor denervation (CBRX) or aortic baroreceptor denervation (ABRX), the reflex changes of HR induced by injecting PE and NP were impaired (P less than 0.01), while the reflex responses in HVP remained unchanged. Despite of the enhanced basal RSNA following ABRX or CBRX, the magnitude of reflex inhibition in RSNA during injecting NP was similar to that before denervation, whereas that of the reflex excitation in RSNA during injecting NP was reduced (P less than 0.05). (3) After complete sino-aortic denervation (SAD), the change of arterial pressure following PE or NP injection was enhanced, but the reflex changes in HR, HVR and RSNA were significantly diminished (P less than 0.001). (4) Vagotomy abolished the residual reflex changes observed after SAD. The results indicate that the aortic and carotid baroreceptors may regulate HR in a simple additive manner, while the aortic baroreceptor seems to be more important. Furthermore, both the aortic and carotid baroreceptors may play important roles for the reflex control of HVR and RSNA, and operate mutually by the way of inhibitory summation. PMID- 2602945 TI - [Arterial baroreflex in the renal hypertensive rabbits]. AB - In 14 anesthetized male rabbits subjected bilateral renal wrapping 12 weeks before, the baroreflex control of heart rate (HR), hindlimb vascular resistance (HVR) and renal sympathetic nerve activity (RSNA) was examined during arterial baroreceptor loading and unloading by injecting phenylephrine (PE) and nitroprusside (NP). The results were as follows: (1) The mean arterial pressure (131 +/- 9 mmHg) of the kidney-wrapped rabbits was significantly higher than that (95 +/- 10 mmHg) of the control rabbits (P less than 0.001). (2) With the buffer nerves intact, the baroreflex control of HR was obviously impaired in the hypertensive rabbits (P less than 0.01), whereas the reflex control of HVR and RSNA remained unchanged as compared with the normotensive rabbits (P greater than 0.05), indicating a dissociation of baroreflex control of HR from that of peripheral circulation. However, in response to local intraarterial injection of PE and NP, the changes in HVR showed no difference between the hypertensive and normotensive rabbits. (3) After aortic or carotid baroreceptor denervation, the reflex control of HR was further reduced in the hypertensive rabbits, and the reflex control of HVR and RSNA was also significantly reduced (P less than 0.01), suggesting an impairment of potential baroreflex regulation of the circulation. It is likely that the changes of baroreflex in hypertensive rabbits may be attributed to the abnormalities in both baroreceptor and central integrating mechanism. PMID- 2602946 TI - [Changes in platelet aggregation and coronary collateral circulation during the early phase of myocardial ischemia in dogs]. AB - Experiments were performed on 18 anesthetized open-chest dogs to observe the changes in platelet aggregation and coronary collateral circulation during the early phase of acute myocardial ischemia. An increase in platelet aggregation rates (PAgR) and a decrease in platelet counts (PC) were found in the blood collected from the ischemic myocardium after coronary occlusion. PAgR was increased by 58.7 +/- 5.6% and PC was reduced by 39.5 +/- 23.6% at 50 min after occlusion (P less than 0.01). Under the condition of controlling aortic blood pressure, collateral coronary vascular capacity (CVC) was not changed (P greater than 0.05), but the effective collateral coronary flow to the ischemic zone, calculated by Wyatt et al's equation, was significantly reduced by 23.5 +/- 9.7% at 50 min after occlusion (P less than 0.05). There was a negative correlation between the changes in PAgR and the effective collateral coronary flow ( r = 0.857, P less than 0.01), and between the collateral indices and infarct size (r = -0.847, P less than 0.01). Abnormal changes in parameters of platelet and coronary collateral circulation after myocardial ischemia were nearly abolished by intravenous injection of aspirin before coronary occlusion. The results suggest that the deleterious changes of platelet aggregation during the early phase of the acute myocardial ischemia may decrease the effective collateral coronary flow significantly and thereby enlarge the infarct size. PMID- 2602947 TI - [Effects of isoprenaline and carbachol on delayed after-depolarization in myocardium]. AB - The effects of isoprenaline and carbachol on the delayed after-depolarization (DAD) induced by acetyl strophanthidin of 2.0 x 10(-7) mol/L were observed in sheep cardiac Purkinje fibers. The amplitude of DAD was enhanced by isoprenaline (1.0--3.0 x 10(-8) mol/L) in a dose-dependent manner and the triggered arrhythmia was induced. Carbachol of 2.0 x 10(-6) mol/L alone had no effect on the amplitude of DAD. When the DAD was enhanced by isoprenaline or the triggered arrhythmia was induced, the same concentration of carbachol could decrease the amplitude of DAD significantly and abolish the triggered arrhythmia. However, carbachol did not attenuate the amplitude of the DAD enhanced by high concentration of calcium, aminophylline or histamine. The results suggest that carbachol can antagonize the enhancement of the DAD caused by isoprenaline. This effect is possibly mediated by activation of the muscarinic receptor, which in turn causes a decrease in the adenyl cyclase activity elevated by the activation of the beta-receptor in the membrane. PMID- 2602948 TI - [Antagonism of morphine analgesia and electroacupuncture analgesia by cholecystokinin octapeptide (CCK-8) administered in periaqueductal gray (PAG) of the rabbits]. AB - We have reported that intracerebroventricular (i. c. v.) injection of 1-4 ng of CCK-8 to the rat produced a remarkable antagonistic effect on morphine analgesia. In order to study the species specificity and the site of action, CCK-8 was microinjected into the PAG of the rabbit, and its influence on morphine analgesia and electroacupuncture analgesia was observed. The latency of the escape response (ERL) to radiant heat focused on the snout was measured as an index of the pain threshold. Microinjections were made via cannulae chronically implanted into the PAG. The drug solutions were delivered in a volume of 1 microliter, at a speed of 0.125 microliter/min. The ERL was measured for a period of 60 or 70 minutes at 10 min intervals. 1. CCK-8 administered unilaterally to the PAG of the rabbit at a dose of 3 ng antagonized the analgesia induced by morphine (4 mg/kg, i. v.) by 73% (P less than 0.001), and reduced the analgesic effect of electroacupuncture by 67% (P less than 0.001). These effects were dose-dependent within the range from 1.5 ng to 6.0 ng. The effect of CCK-8 was reversed by CCK receptor blocker proglumide (4 microliters, intra-PAG injection). Unsulfated CCK-8 (CCK-us) had no effect in this regard. These results indicate that in the PAG of the rabbit, exogenously administered CCK-8 was capable of antagonizing opioid analgesia by the activation of CCK receptors. 2. Two groups of rabbits were given with morphine (2 mg/kg, i. v.) and simultaneous injection of CCK-8 antiserum (CCK-AS, 1 microliter) or normal rabbit serum (NRS) into the PAG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2602949 TI - [Effect of a human fetal liver factor in suppression of HL-60 cell growth in vitro]. AB - Two kinds of HL-60 cell growth suppressors present in human fetal liver were studied. One is the known arginase which shows non-specific suppression on the growth of HL-60 cells and human granulocyte-macrophage progenitors (CFU-GM), and the other, a new species of suppressor with a lower molecular weight (less than 10,000 daltons), shows preferential suppression on HL-60 cell growth, but less suppressive effect on the growth of CFU-GM. PMID- 2602950 TI - [Intracerebroventricular administration of hypertonic saline inhibits the reabsorption of water and sodium in the proximal tubule]. AB - In anaesthetized rats with unilateral section of the renal nerve, the effect of intracerebroventricular (icv.) administration of hypertonic saline on the reabsorption of water and sodium in the proximal tubule was investigated, using the lithium clearance method. After icv. administration of hypertonic saline, the lithium clearance (CLi to glomerular filtration rate (GFR) ratio increased from 0.37 +/- 0.04 to 0.51 +/- 0.05 (P less than 0.01) in the denervated kidneys and from 0.26 +/- 0.03 to 0.31 +/- 0.04 (P less than 0.05) in the innervated kidneys, respectively. GFR, urine flow rate (V), urinary sodium excretion (UNaV) and urinary potassium excretion (UkV) increased in both innervated and denervated kidneys, the increments of V, UNaV and UkV being greater in the denervated kidneys than in the innervated kidneys. In micropuncture experiments, icv. administration of hypertonic saline caused an increase in proximal tubule flow rate, from 24.42 +/- 1.84 nl/min to 31.86 +/- 3.09 nl/min, without significant change in proximal tubule fluid osmolality in the innervated kidneys. These data support the notion that the diuresis and natriuresis induced by icv. administration of hypertonic saline in the anaesthetized rat result from an increase in GFR and a decrease in the reabsorption of water and sodium in the proximal tubule. Humoral factors are probably involved in these responses. PMID- 2602951 TI - [Mechanisms underlying depressor and bradycardia effects of A1-excitation in rats]. AB - In chloral hydrate-anesthetized, tubocurarine-immobilized and artificially ventilated rats, the following results were observed: (1) Microinjection of sodium L-glutamate (Glu) into A1 area induced a significant fall in blood pressure and heart rate. (2) Bilateral vagotomy markedly reduced the magnitude of the depressor and bradycardia effects of Glu-injection into A1. (3) Injection of phentolamine or propranolol into bilateral RVL reduced the depressor effect of Glu-injection into A1. Naloxone-injection into RVL had no significant influence on cardiovascular effects of A1-excitation, but injecting bicuculline into RVL could reverse both depressor and bradycardia effects of A1 area. The results suggest that A1 exerts its cardiovascular effects mainly via RVL, and the alpha-, beta- and GABA-receptors within RVL (but not opiate receptors) mediate the hypotension effect of A1 area, while GABA-receptors play an important role in mediating the bradycardia effect of the A1 area. PMID- 2602952 TI - [Mechanisms underlying depressor and bradycardia effects of A5-excitation (compared with that of A1-excitation) in rats]. AB - Experiments were performed under the same condition described in the accompanying paper. (1) Injection of sodium L-glutamate (Glu) into A5 area of rat induced depressor and bradycardia responses, as Glu-injection into A1 area did. (2) Bilateral vagotomy also markedly attenuated the cardiovascular effect of Glu injection into A5. (3) Influences of the receptor blockers injected into rostral ventrolateral medulla (RVL) on the depressor and bradycardia responses of Glu injection into A5 were slightly different from those of the same receptor blockers administered into RVL: phentolamine, propranolol, naloxone and bicuculline all markedly reduced the depressor and bradycardia effects of A5 excitation (propranolol and bicuculline even reversed these effects). These results indicate that not only alpha-, beta-, GABA receptors, but also opiate receptors mediate the depressor and bradycardia effects of A5. PMID- 2602953 TI - [Factors affect Na(+)-Ca2+ exchange in rat's cardiomyocytes and protein reconstituted liposomes]. AB - Rat's Ca-resistant ventricular myocytes and reconstituted liposomes of canine cardiac sarcolemma were used in analysing factors affecting Na(+)-Ca2+ exchange system. Decrease in extracellular (extravesicular) Na+ or increase in intracellular Na+ by inhibition of the Za(+)-K(+)-ATPase with ouabain stimulated the Na(+)-Ca2+ exchange. Mn2+, an antagonist of Na(+)-Ca2+ exchange, dose dependently inhibited the Na(+)-dependent Ca2+ uptake. However, verapamil had no effect on it. Arachidonic acid and lipid peroxides caused by incubation with-H2O2 significantly stimulated Na(+)-Ca2+ exchange in a dose-dependent fashion. PMID- 2602954 TI - [Pharmacological deaggregation of platelet aggregation]. AB - Antagonists of increasing concentrations were added to PRP which had exhibited irreversible aggregation and the extent of deaggregation was determined. Several classes of platelet antagonists with different mechanisms have been undertaken to reverse platelet aggregation induced by ADP, collagen, arachidonic acid, U46619 and PAF. The results indicate that maintenance of platelet aggregation is a complex phenomenon involving multiple mechanisms which depend on agonists. Maintenance of ADP induced aggregation requires exogenous calcium and active intracellular calcium mobilization. Active intracellular calcium mobilization appears to be essential for maintaining aggregation by PAF, U46619 and arachidonic acid. But additional pathway may be operative in maintaining collagen induced aggregation. Calmodulin inhibitors with multiple actions are effective deaggregators. Calmodulin plays a role in maintaining platelet aggregation. The present study indicates that the ability of various antagonists to reverse platelet aggregation is closely related to three factors: 1) agonists used to stimulate platelet, 2) the time period following the initiation of platelet aggregation and 3) the kinds of antagonists used. PMID- 2602955 TI - [Functional plasticity of frontal neurons in rhesus monkeys during performing visual discrimination go/no-go task]. AB - We previously reported that frontal neurons in monkeys may be essentially responsive to the biological meanings of the stimuli in a task, rather than to their physical attributes. To examine this hypothesis, activity of single neurons was recorded from the frontal cortex of monkeys (Macaca mulatta) while performing a visual delayed discrimination GO/NO-GO task (task I, n = 2) and a visual discrimination response GO/NO-GO task (task II, n = 2), respectively. A green or red light presented in the period 2 of task I and in the period 4 of task II was used as a cue to guide the monkeys' behaviour. The same green/red light was presented in the period 2 of task II as well, but this was not a cue and had no definite meanings in the task. The monkeys were trained to watch attentively the panel in period 3 of both tasks. A total of 163 task-related neurons were recorded: 98 in task I and 65 in task II. Although neuronal responses appeared in all periods of both tasks, the majority of the responses (70% of the total) were in the periods 2 and 3 of task I, and in the periods 3 and 4 of task II. Furthermore, in the period 2 of task I and period 4 of task II, but not in the period 2 of task II, most of neurons were responsive exclusively to either green or red light. The results support the hypothesis stated above, and suggest that the responses of the frontal neurons to signal stimulation are gradually established in the course of learning, and possess highly developed functional plasticity. PMID- 2602956 TI - [The adaptive cytoprotection of exocrine pancreas in rats]. AB - A model of acute necroto-hemorrhagic pancreatitis was prepared by injecting 5% sodium taurocholate-trypsin solution directly into the pancreatic duct of the rat. Fourty eight hours before the preparation of acute pancreatitis, intraductal injection of 0.1%, 0.2% or 0.4% sodium taurocholate-trypsin solution as mild irritant was able to decrease the mortality to 27%, 17% and 17% respectively. The maximal elevation of the serum amylase concentration in acute pancreatitis was decreased to 43%, 47% and 54%, respectively. Microscopic examination of the pancreatic tissue of the rats which were alive after pretreatment of mild irritants showed that the acute pancreatitis was milder and there was a tendency to change to chronic pancreatitis. Thus, we conclude that there is a phenomenon of adaptive cytoprotection on the exocrine pancreas in rats. The mechanisms of the phenomenon remain to be explored. PMID- 2602957 TI - [The consumption of fibronectin content in coronary artery stenosis in dogs]. AB - Changes in plasma fibronectin (Fn) content of the coronary sinus were observed in coronary artery stenosis of dogs. The results showed that coronary artery stenosis produced an acute inflammatory response and decreased Fn when coronary artery stenosis was more than 75%, which was associated with an increase in platelet aggregation and activation. Histopathologic examination confirmed the presence of damaged endothelial cell and capillary and showed the adhesion of leukocyte and platelet also. The results suggest that injured coronary artery may impair protective function in coronary circulation. PMID- 2602958 TI - [The role of sulfhydryls in indomethacin-induced gastric mucosal injury in rats]. AB - The possible role of sulfhydryls in indomethacin-induced gastric mucosal injury was studied. No significant decrease of the contents of both non-protein and protein-binding sulfhydryls was observed in the gastric mucosa during injury. Indomethacin-induced gastric ulcer was inhibited by cysteamine of 132 and 264 mumol, i.g. or of 132 mumol, s.c. by 82%, 92% and 75% respectively. Such protective effect was not observed with cysteine in equal molar dose. Subcutaneously injected cysteamine (132 mumol) inhibited gastric acid secretion by 46% in indomethacin-treated rats, while no effect was observed on acid secretion when cysteamine was given intragastrically. Cysteamine, given through both routes, did not affect gastric barrier mucus secretion. It is suggested that sulfhydryls in gastric mucosa are not involved in the mechanism of indomethacin induced injury and that the potent cytoprotective effect of cysteamine against indomethacin-induced ulcer maybe not caused by its sulfhydryl group. PMID- 2602959 TI - [Antidiarrheals]. PMID- 2602961 TI - [Health education in the school]. PMID- 2602960 TI - [Preparations before bandaging]. PMID- 2602962 TI - [Chemotherapy at home, pain and its treatment]. PMID- 2602963 TI - [Education of professional nurses in Europe]. PMID- 2602964 TI - [Information and profession. Perception of the profession in the media]. PMID- 2602965 TI - [Health policy in industry. Towards true preventive policy in the media]. PMID- 2602966 TI - [Prevention and treatment of decubitus ulcers]. PMID- 2602967 TI - [Nursing: vocation of yesterday or profession of tomorrow]. PMID- 2602968 TI - [Computerization of health charts]. PMID- 2602969 TI - [AIDS and parenthesis]. PMID- 2602970 TI - [Responses to the nutritional needs of cancer patients]. PMID- 2602971 TI - [Nursing care in a hemodialysis unit]. PMID- 2602972 TI - [Report of the National Commission of Nurses. Summary and commentaries]. PMID- 2602973 TI - [Expectorants]. PMID- 2602974 TI - [Indwelling urinary catheters. The various connecting systems]. PMID- 2602975 TI - [Legislative texts and prospects]. PMID- 2602976 TI - [Occupational health nurses. Role and education]. PMID- 2602977 TI - [A description of the functions of an industrial nurse]. PMID- 2602978 TI - [The "ergoscope"--use by the occupational health nurse]. PMID- 2602979 TI - [The evaluation and prevention of toxic risks. Role of the nurse in the occupational health team]. PMID- 2602980 TI - [The occupational health nurse]. PMID- 2602981 TI - [The industrial nurse and first aid]. PMID- 2602982 TI - [Industrial toxic risks. Role of the occupational health nurse]. PMID- 2602983 TI - [AIDS prevention--the prime role of occupational medicine]. PMID- 2602985 TI - [Occupational health nurses and the European Common Market]. PMID- 2602984 TI - [An association of previous drinkers within a business. Role of an occupational health nurse]. PMID- 2602986 TI - [Joint practice in the professional world of nursing service]. PMID- 2602987 TI - [Sleep and its disorders]. PMID- 2602988 TI - [The value of injectable forms of liquids in oncology]. PMID- 2602989 TI - [Exercising the right to strike by nurses]. PMID- 2602990 TI - [An upsetting promotion]. PMID- 2602991 TI - [Collective reactions in disasters]. PMID- 2602992 TI - [Emotional reactions in decision makers, rescuers and caretakers]. PMID- 2602993 TI - [Managing crisis--informing, communicating]. PMID- 2602994 TI - [Disasters and mass media]. PMID- 2602995 TI - [Psychological victims of disasters]. PMID- 2602996 TI - [The reform of nursing studies. Elements of reflection and propositions]. PMID- 2602998 TI - [Psychosociological dimensions of disasters]. PMID- 2602997 TI - [Narcissism]. PMID- 2602999 TI - [Continuing education action. Session on community work]. PMID- 2603000 TI - [The team and the prescription]. PMID- 2603001 TI - [The community psychiatric nurse and the suicidal patient]. PMID- 2603002 TI - [The mentally wounded. Pathological reactions and mental involvement in victims of disasters]. PMID- 2603003 TI - [Loss of memory, of equilibrium ... and of urine]. PMID- 2603004 TI - [The psychologic impact of somatic diseases]. PMID- 2603005 TI - [The crisis of aging]. PMID- 2603006 TI - [The countertransference attitude towards aging]. PMID- 2603007 TI - [Some prescription rules for the elderly]. PMID- 2603008 TI - [The therapeutic course in gerontological psychiatry]. PMID- 2603009 TI - [Chemotherapy in dementia]. PMID- 2603010 TI - [Specific care in gerontologic psychiatry. Some guidelines]. PMID- 2603011 TI - [Gerontological psychiatry]. PMID- 2603012 TI - [The uncertainty of "polyvalence"]. PMID- 2603013 TI - [The word, the body and the cure]. PMID- 2603014 TI - [Senile dementia and its pitfalls]. PMID- 2603015 TI - [Depression in the elderly]. PMID- 2603016 TI - [Trends in the development of research on the organization of ambulatory care]. AB - The data on content--analysis of publications in journals of "Soviet Public Health" and "Public Health of the Russian Federation" indicate that problems of ambulatory health care organization can be regarded as the developing trend in science. The research devoted to the organization of out-patient care, issues of management in polyclinics, solving of their organizational and technical problems fails to keep pace with practice and requires intensification. Over recent years scientific interest for dispensarization has heightened dramatically. Apparently this trend will be developing rather intensively and will lead to changes in internal structure of research. Priority will be given to the research on the problems of computer-based management of dispensarization and evaluation of health of large groups of population with the help of automated systems along with further development of theory of dispensarization. PMID- 2603017 TI - [Several current problems of prevention]. AB - The article examines the strategy of health protection of the population: the formation of demand for health-promoting activities through establishing the priority of health in public relations; the necessity of using the new methodology in screening for health, permitting to determine its level in practically healthy persons; new organization of health-promoting infrastructure; the issues related to the training of family physicians in the field of health promoting medicine. PMID- 2603018 TI - [International research project, "The effectiveness of stomatological care and stomatological status of the population"]. PMID- 2603019 TI - [Attitude to health of persons with higher education]. PMID- 2603020 TI - [A system of advanced training of administrators in the field of maternal and child health]. AB - The article summarizes the first experience gained by the Chair of Social Pediatrics established in 1986 at the Faculty of Postgraduate training of Physicians to LPHI. More than 500 pediatric public health administrators have been trained. The educational programme with due regard for peculiarities of different population groups is provided. The Chair is helpful in rendering assistance to public health bodies. PMID- 2603022 TI - [Hemosorption in myasthenia gravis]. PMID- 2603021 TI - [Extracorporeal regulation of platelet aggregation in acute myocardial infarction]. PMID- 2603023 TI - [Pathogenesis of eczema and psoriasis]. PMID- 2603024 TI - [Osteogenesis imperfecta of the late type]. PMID- 2603025 TI - [Metastatic endophthalmitis in diabetes mellitus]. PMID- 2603026 TI - [Recurrence of torsion of the epiploica of the sigmoid]. PMID- 2603027 TI - [Surgical and rehabilitation treatment of Dupuytren's contracture]. PMID- 2603028 TI - [Angioleiomyoma of the large-intestinal mesentery complicated by diffuse peritonitis]. PMID- 2603029 TI - [Sclerocystic ovary syndrome associated with tumors of the adrenal medulla]. PMID- 2603030 TI - [Serum gastrin levels in various diseases of the digestive organs]. PMID- 2603031 TI - [Late outcome of neurocirculatory asthenia]. PMID- 2603032 TI - [Cyclic epilepsy in women]. PMID- 2603033 TI - [Filtration exchange plasmapheresis in diffuse suppurative peritonitis]. PMID- 2603034 TI - [Individual sensitivity to hypolipidemic factors in ischemic heart disease]. PMID- 2603035 TI - [Gas-chromatographic analysis of hypercholestanol in the bile and its role in the pathogenesis of cholelithiasis]. AB - The cholestanol/cholesterol ratio in the bladder and liver bile was estimated by capillary gas-liquid chromatography in patients with dyskinesia of the gallbladder, chronic acalculous cholecystitis, and chronic calculous cholecystitis. Cholesterol biliary calculi and their surface and intermediate layers and the core were examined either. The authors came to a conclusion that cholestanol/cholesterol ratio in the bladder and liver bile reflected the progress of liver cholesterol metabolism starting from the early stages of cholelithiasis to the formation of cholesterol biliary calculi. Therefore hypercholestanolcholia should be considered as an indicator of the risk of cholesterol biliary calculi development. PMID- 2603036 TI - [Evaluation of sympathetic and parasympathetic mechanisms of regulation in autonomic paroxysms]. AB - Patients with autonomic paroxysms (AP) and hysterical attacks (HA) have been examined with the use of ECG wave structure analysis. Domination of slow and reduction of respiratory waves reflect the background stress of the sympathetic and insufficiency of vagal mechanisms with rigidity of heart rhythm pulsation structure in AP patients or excessive reactivity to emotional stress in HA patients. The efficacy of beta-adrenoblocker anaprilin and diazepam and the inefficacy of alpha-adrenoblocker phentolamine for AP treatment are validated. PMID- 2603037 TI - [Microcirculation in the diaphyses of tubular bones after intramedullary osteosynthesis]. PMID- 2603038 TI - [Antibodies to type I and II collagen in rheumatoid arthritis and chronic cicatricial stenosis of the larynx and trachea in children]. AB - Enzyme immunoassay with highly purified human collagen preparations and low (1:10) dilutions of sera detected an increased specific immune reaction mostly on collagen denaturated forms in 50% of 49 patients with rheumatoid arthritis. No correlation was detected between the level of humoral immune response and the major clinical parameters except those reflecting the disease progress. Similar investigation of sera from children with chronic cicatricial stenoses has revealed a group of patients with significantly elevated level of anticollagen humoral immune response, though in these patients this response is probably not specifically associated with collagen. PMID- 2603039 TI - [The role of morphologic studies in the diagnosis of malignant neoplasms]. PMID- 2603040 TI - [Chronic alcoholic intoxication at an internal disease clinic]. PMID- 2603041 TI - [Clinico-laboratory indicators in the prognosis and treatment of chronic obstructive bronchitis]. PMID- 2603042 TI - [Physical rehabilitation in diabetes mellitus]. PMID- 2603043 TI - [Clinico-electromyographic studies of muscular reinnervation in injuries of the peripheral nerves]. PMID- 2603044 TI - [Empty sella syndrome in benign intracranial hypertension]. PMID- 2603045 TI - [A case of familial atypical pseudohypertrophic proximal progressive muscular dystrophy]. PMID- 2603046 TI - Three-dimensional motion analysis of the cervical spine with special reference to the axial rotation. AB - The purpose of this study is to obtain basic data on the rotational motion of the cervical spine. Twenty normal men aged 25 to 31 years were investigated. Biplanar roentgenograms of the neck with the head held in neutral and maximally rotated positions were taken in a reference frame. Three sets of x-ray films were measured using a three-dimensional analysis system composed of a digitizer and a personal computer. Total axial rotation was 105 degrees on an average between the occiput and the C7 vertebra. Seventy percent of the total axial rotation occurred between the occiput and the C2 vertebra. Each motion segment between the C2 and C7 vertebrae showed from 4 degrees to 8 degrees rotation on an average. When the head was rotated, lateral bending occurred by coupling in the same direction as rotation at each segment below the C3-C4 level, and in the opposite direction above the C2-C3 level. At the same time, flexion took place by coupling at each segment below the C5-C6 level, and extension above the C4-C5 level. PMID- 2603047 TI - Numerical evaluation of symptoms in cervical myelopathy by quantification theory III (Hayashi). AB - The authors applied Hayashi's quantification theory III, a mathematical approach for quantification of qualitative data to evaluate cervical myelopathy in 81 patients who had been surgically treated. More of these patients recovered from sensory disturbances than from motor disturbance. The size of the spinal canal was correlated with the severity of the preoperative symptoms of the myelopathy, but not with the surgical results. The surgical results were correlated with the duration of the disease but not with the age of the patient. The most predictable surgical result obtained by the use of multiple regression analysis was that of the leg motor symptom. PMID- 2603048 TI - Magnetic resonance imaging of upper cervical disorders in rheumatoid arthritis. AB - Upper cervical spine was examined with magnetic resonance imaging (MRI) and conventional roentgenograms in 55 patients with rheumatoid arthritis. The MRI findings were compared with various values determined in roentgenograms: the atlanto-dental interval (ADI), the space available for the spinal cord (SAC), and the Ranawat and Redlund-Johnell values. In patients with vertical settling (VS), MRI showed medullary compression in all those with abnormal Redlund-Johnell values and Ranawat values of 7 mm or less. In patients with anterior atlanto axial subluxation, compression of the upper cervical cord was observed in all patients with SAC of 13 mm or less and many of those with ADI of 8 mm or greater. This study indicated that medullary compression can be estimated by these values determined in roentgenograms of the cervical spine. PMID- 2603049 TI - Unstable cervical spine in athetoid cerebral palsy. AB - The manifestations and pathomechanism of cervical instability of the athetoid neck in cerebral palsy (CP) patients was clarified in this study by means of static and dynamic x-ray analysis. Instability was defined as follows: 1) listhesis indicating anterior or posterior slip of more than 3 mm and/or 2) sagittal rotation between two vertebrae beyond the normal range measured by Penning. Cervical instability fitting this definition mainly took place in the upper and middle cervical disc levels, such as C3-4, C4-5, and/or occasionally C5 6. These coincide with the disc levels adjacent to the apex of the lordotic curve and/or those around the transitional vertebrae between the two reversed curves that render the cervical spine S-shaped in athetoid CP. A large facet angle at the apex vertebra facilitated anterior and/or posterior listhesis of the vertebrae. Conversely, a sudden decrease in the facet angle around the transitional vertebra in S-shaped curves precipitated deflection of the spine and increased sagittal rotation at this level. In addition to these structural abnormalities, rapid and repetitious neck movements seemed to accelerate the progression of cervical instability in athetoid CP patients. PMID- 2603051 TI - Analysis of cervical instability resulting from laminectomies for removal of spinal cord tumor. AB - Thirty-four patients with cervical cord tumor were followed in order to investigate the incidence of postoperative deformity or instability after laminectomies. Seven cases (20%) presented cervical instability, including three cases that required spinal fusion. Analysis of these cases revealed the identification of some risk factors that are involved in the pathogenetic mechanism of cervical instability, which are: age at operation, preoperative curvature in neutral position, number of removed laminas, C2 laminectomy, and destruction of facet joints. The number of these risk factors present in each case was shown to be directly related to the incidence of cervical instability. Patients who had not developed instability demonstrated 1.2 factors on average, while patients who had developed instability showed a mean of 2.5 factors. Patients who had additionally required spinal fusion presented 3 risk factors, including C2 laminectomy and destruction of facet joints. PMID- 2603050 TI - Posterior extensive simultaneous multisegment decompression with posterolateral fusion for cervical myelopathy with cervical instability and kyphotic and/or S shaped deformities. AB - From June 1978 to May 1988, posterior decompression with posterolateral fusion was performed at Tenri Hospital on 63 cases of cervical myelopathy with instability and/or malalignment including kyphotic and/or S-shaped deformities. Among 46 cases followed up for more than 1 year, 41 cases (89.1%) improved; 21 cases (45.7%) were rated excellent, six (13%), good; 14 (30.4%), fair; one (2.2%), unchanged; and four (8.7%), poor. On x-ray examination, bone consolidation at the bone implanted area was satisfactory in 30 cases (65.2%). Cervical instability disappeared at 55 cervical interspaces of 40 cases (78.6%). Displacement at unstable interspace disappeared or improved at 49 of 61 cervical interspaces (80.3%). Although cervical kyphosis or S-shaped deformity could not be improved, accelerated progression of these deformities appeared to be prevented. PMID- 2603052 TI - Dome-like expansive laminoplasty for the second cervical vertebra. AB - The second cervical vertebra (C2) is in a pivotal position for the alignment and stability of the cervical vertebrae as a whole. Since its spinal canal is wider at the cranial and narrower at the caudal end, a dome-like excision of the inner side of the spinal canal from the caudal toward the cranial end results in the decompression of the lesion, preserving the dorsal part of the C2. The authors performed this C2 dome-like expansive laminoplasty on 33 patients (25 cases of the ossification of the posterior longitudinal ligament, six of developmental spinal canal stenosis, and two of spondylosis) and kept them under follow-up observation, which ranged from 1 to 7 years (mean, 3.5 years). The result was satisfactory in terms of the decompression and stability of the cervical vertebrae: even 5 years after the operation, no osteogenesis was noted in the expanded spinal canal to induce compression again. It thus may be concluded that this method is good enough to replace conventional laminectomy. PMID- 2603053 TI - Mandible and tongue-splitting approach for giant cell tumor of axis. AB - In two cases with a giant cell tumor of the axis, the mandible and tongue splitting approach permitted excision of the tumor and anterior fusion of the spine from the atlas to the third cervical vertebra. With this approach, there is no need to extend or rotate the cervical spine during the operation. In addition, the operative field extends from the clivus to the fourth cervical vertebra, and safe and sufficient anterior decompression is possible. Although this approach has some disadvantages, contemporary techniques of intravenous hyperalimentation and postoperative respiratory management provide a solution to these problems. Thus, this approach should always be considered for patients requiring extensive anterior decompression of the craniovertebral junction or upper cervical spine. PMID- 2603054 TI - Clinical study of dissociated motor weakness following anterior cervical decompression surgery. AB - C5 segment motor loss (deltoid muscle) after a cervical spinal operation, either anterior decompression or posterior decompression, has rarely been reported. However, most such cases are diagnosed immediately after surgery, and they appear to be due to inadequate surgical technique or insufficient decompression. Recently, the authors have experienced three cases in which weakness of the deltoid muscle started several days following anterior cervical decompression surgery. On the basis of postoperative plain films, myelography, and computed tomography (CT) myelography, the cause of the motor weakness was considered to be C5 root disturbance due to postoperative malalignment of the cervical spine, which gradually increased. The malalignment of the cervical spine seemed to be due to weakness of iliac bone grafts, inadequate design of the bone graft and recipient site, and insufficient postoperative fixation. To prevent this malalignment, eg, lateral inclination of the bone graft to axial rotation deformity, adequate bone graft design is required. The authors have been performing internal fixation using sapphire screws on cases in which fusion extending over four vertebral bodies is required. PMID- 2603055 TI - An experimental study of spinal cord evoked potentials and histologic changes following spinal cord heating. AB - To study the safety of hyperthermia cancer treatment, canine spinal cords were heated with radio waves to between 43 C and 47 C for 30 minutes. Spinal cord evoked potentials (SCEP) studied by epidural recording after epidural stimulation showed shortened latency and unchanged amplitude at 44 C or below. At 45 C or above, reduction of amplitude combined with shortened latency was observed, a phenomenon that has not hitherto been reported. After heating to 45 C, SCEP recovered with the reduction of temperature, but histologic examinations showed pigment exudation, vacuolation, and hemorrhage. These results suggest that tolerable spinal cord temperature should not exceed about 44 C. PMID- 2603056 TI - Effects of compression on intraradicular blood flow in dogs. AB - In order to study the pathogenesis of radiculopathy, the authors investigated the effects of mechanical compression of the intraradicular blood flow in adult dogs using the electrochemically generated hydrogen washout method. The blood flow was more severly disturbed at the proximal side than the distal side when the nerve root was compressed, but when the clamp was released, the blood flow on the proximal side was almost completely restored, whereas the flow on the distal side did not recover and stayed at the reduced level. These phenomena can be explained both by the direction of blood flow in the radicular vessels and by the peculiar structure of the nerve root, which is soaked in cerebrospinal fluid. PMID- 2603058 TI - Histopathologic study on tumor infiltration into the intervertebral disc. AB - This study was performed in order to understand the reasons why the metastasis of malignancy into the disc is rare in contrast to the commonly seen vertebral metastasis. By histopathologic studies of 14 vertebral columns with vertebral metastases of various malignant tumors and 616 disc specimens, the authors found three pathways for an intravertebral tumor to invade into the adjacent disc: 1) direct infiltration from the rim of the vertebral body not covered by the cartilagenous plate, 2) infiltration from the side of the vertebral body close to the vertebral corner, through the subspace beneath the longitudinal ligament, and 3) hematogenous invasion via small vessels in the subspace beneath the longitudinal ligament. The authors concluded that the cartilagenous plate between the vertebral body and the disc as well as high intradiscal pressure would be acting as a barrier against tumor invasion from the vertebral body into the disc, and suggests that gradual increase of capillaries in the disc with age may enhance hematogenous invasion into the disc in rare occasions. PMID- 2603057 TI - Water diffusion pathway, swelling pressure, and biomechanical properties of the intervertebral disc during compression load. AB - The behavior of water in the intervertebral disc of pig tail and its physiologic and biomechanical properties were investigated in relation to compression load. The water content, chemical composition, and swelling pressure in the intervertebral disc were measured, and the mechanism of the generation of the swelling pressure in relation to compression load stress was studied. The swelling pressure, through regulation of the water content of the disc and the resistance of the external load, differs with the region of the intervertebral disc. In the nucleus pulposus and the inner layer of the anulus fibrosus, the swelling pressure rises in proportion to the load, but few changes occur in the outer layer of the anulus fibrosus, and the constant pressure environment is thus maintained. The tritiated water (3H2O) uptake of the disc under various loads was measured. The molar partition coefficient of tritiated water is almost equal to 1 even under a compression load, which suggests that water is freely exchangeable. The diffusion of 3H2O in the intervertebral disc was traced using two pathway models: the perianular route and the end-plate route. The diffusion of water in the unloaded disc for both uptake and washout was about 2 to 3 times larger in the perianular route than in the end-plate route. Under load, the water diffusion was inhibited in both pathways. The relation between the load and displacement revealed viscoelastic properties indicating creep and stress relaxation. Young's modulus and the stiffness increased with a rise in load speed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2603059 TI - Biomechanical evaluation of spinal fixation devices. Part III. Stability provided by six spinal fixation devices and interbody bone graft. AB - The three-dimentional stability provided by six spinal fixation devices with or without interbody bone graft has been studied in an in vitro biomechanical model using five-vertebral (T11-L3) fresh cadaveric thoracolumbar specimens. An injury was created at T12-L1 by complete transection of the posterior elements and posterior half of the intervertebral disc, leaving the anterior half of the intervertebral disc and anterior longitudinal ligament intact. The three dimensional rotations and translations, measures of biomechanical instabilities, were determined under physiologic loads for the intact spine and the spinal constructs, ie, injured spine plus instrumentation. The tested devices were: Harrington reverse ratchet rods (HR); Luque rectangle rod (LR); Kaneda device without transverse fixator (KD); Kaneda device with transverse fixators (KT); transpedicular external fixator (EF). In addition, stability tests were performed for KT, EF, and Harrington compression rods with interbody bone graft following a corpectomy (KTB, EFB, and HCB). The constructs were more stable than the intact spine under the four loads in the following order: flexion: EFB, HCB, EF, HR, LR, KTB, and KT; extension: EFB, LR, EF, KTB, HR, and KT; lateral bending: KTB, KT, EFB, KD, EF, HCB, and HR; and axial rotation: EFB. PMID- 2603060 TI - Three-dimensional movements of the whole lumbar spine and lumbosacral joint. AB - Knowledge of the normal movements of whole lumbar spine and lumbosacral joint is important for evaluating clinical pathologic conditions that may potentially produce unstable situations in these regions. At present there are few studies that report systemic three-dimensional movement analysis of these regions. The purpose of this in vitro study was to quantitatively determine three-dimensional movements of the whole lumbar spine and lumbosacral joint. Ten fresh human cadaveric spine specimens including from L1 to sacrum (six specimens) and ilium (four specimens) were studied. Pure moments of a maximum of 10 N-m were applied incrementally. Parameters of neutral zone, elastic zone, and range of motion for rotations as well as for translations were measured. Neutral zones for flexion extension, right/left axial torque, and right-left lateral bending were, respectively: 1.6 degrees, 0.9 degrees, and 1.4 degrees (L1-2); 1.0 degrees, 0.8 degrees, and 2.0 degrees (L2-3); 1.4 degrees, 0.7 degrees, and 1.4 degrees (L3 4); 1.8 degrees, 0.4 degrees, and 1.6 degrees (L4-5); 3.0 degrees, 0.4 degrees, and 1.8 degrees (L5-S1). Ranges of motion for flexion, extension, axial torque (one side), and lateral bending (one side) were, respectively: 5.8 degrees, 4.3 degrees, 2.3 degrees, and 4.9 degrees (L1-2); 6.5 degrees, 4.3 degrees, 2.6 degrees, and 7.0 degrees (L2-3); 7.5 degrees, 3.7 degrees, 2.6 degrees, and 5.7 degrees (L3-4); 8.9 degrees, 5.8 degrees, 2.2 degrees, and 5.7 degrees (L4-5); 10.0 degrees, 7.8 degrees, 1.4 degrees, and 5.5 degrees (L5-S1). Neutral zone values were small except for flexion at L5-S1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2603061 TI - Classification by position of dorsal root ganglia in the lumbosacral region. AB - In order to determine the incidence of the proximally placed L5 and S1 dorsal root ganglia, 144 patients with lumbosacral radiculopathy were investigated. All of the patients underwent nerve root infiltration for depicting the nerve root. Using some bony landmarks on the anteroposterior radiculogram, the dorsal root ganglia were classified into three types: intraspinal, intraforaminal, and extraforaminal. The intraspinal type was further subdivided into subarticular and sublaminar types. The intraspinal type is more common in the S1 than in the L5 root, regardless of age and sex. Although the proximally placed dorsal root ganglia may offer a locus minoris resistantiae for neural irritation and compression, its role for symptom production of radiculopathy should be further analyzed. PMID- 2603062 TI - The configuration of the laminas and facet joints in degenerative spondylolisthesis. A clinicoradiologic study. AB - The configuratory variation of laminas and facet joints was discussed with reference to development of degenerative spondylolisthesis and its clinical symptoms. The authors have classified the configuration of laminas in the lower lumbar spine into three different types, (WI, W2, and N), based on the two characteristic features of the lamina: 1) whether or not the inferior articular processes are wider than the waist part of the lamina, and 2) whether or not the facet joint spaces can be recognized on plain anteroposterior (AP) radiographs. Types W1 and W2 laminas have the laterally prominent inferior articular processes, but the facet joint spaces are not visible on AP view in Type W1. Type N lamina has narrow inferior articular processes and its facet joint spaces can be recognized on AP view. Computed tomography (CT) scanning revealed that the direction of facet joints of Types W2 and N laminas was more sagittal than that of Type W1, and that all of Type N laminas with the narrow inferior articular processes have a sagittal facet. Type N lamina was rarely seen in the 257 controls, but was quite frequent in degenerative spondylolisthesis, 3.5% and 45.8%, respectively. Patients with Type N laminas were likely to show more severe clinical symptoms such as difficulty walking and neurologic deficits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2603063 TI - "Masonry arch" model of the spine. PMID- 2603064 TI - [Metabolic and ultrastructural changes in the myocardium during heart arrest in patients undergoing surgery for ischemic heart disease]. AB - The authors give an account of metabolic changes in the ultrastructure of the myocardium which develop during cardioplegic arrest of the heart muscle by cold during aortocoronary reconstruction operations. Using the technique of arteriovenous differences before myocardial ischemia and after its termination, the assessed differences in arterial blood and blood from the sinus coronarius as regards the blood sugar level, lactate, pyruvate, potassium, phosphorus, unsaturated fatty acids and triglycerides. The results revealed a marked disorder of the carbohydrate and ion metabolism and severe impairment of the ultrastructure of the heart muscle during cardiac arrest. PMID- 2603065 TI - [A study of the immune status in patients before heart surgery using the Imunoskintest Sevac kit]. AB - By means of a Immunoskintest Sevac kit the authors examined 99 patients who were subjected to heart surgery with extracorporeal circulation. In the group of patients with an index of more than 1.0 were 7% postoperative infectious complications, in the group with an index smaller than 1.0 there were 19% and in the group of patients with anergy and relative anergy there were 66% infectious complications after operation. The authors consider as risk patients those where anergy or relative anergy was proved, as well as patients with an index lower than 1.0 and a weak response to 2-3 antigens. In risk patients it is essential to make a detailed immunological examination and to correct in a suitable way their immunodeficiency, e. g. by administration of transfer factors. From the results ensues moreover that the immune response of patients, and thus also the development of postoperative infectious complications, is related to the patient's age and the presence of rheumatic disease. PMID- 2603066 TI - [Treatment in a patient with multiple brain abscesses]. AB - The authors present an account of successful treatment of a 23-year-old patient with multiple relapsing abscesses of the right cerebral hemisphere of otogenic origin by repeated punctures. They emphasize the importance of computed tomography for assessment of the type of lesions, their localization and follow up of the disease. PMID- 2603067 TI - [Pulmonary sequestration]. AB - In a group of 11 patients with pulmonary sequestration (7 men and 4 women) nine times lower lobectomy was performed and twice segmental resection of the basal segments of the lower lobe. Three times severe haemorrhage from the atherosclerotic degeneratively altered artery supplying the pulmonary sequester was recorded. None of the patients died. No relapse was observed. An essential part of the preoperative examination is angiography of the lungs which reveals reliably an atypical course of the artery for the pulmonary sequester. PMID- 2603068 TI - [Traumatic ruptures of the diaphragm]. AB - The authors present a group of three traumatic ruptures of the diaphragm and call attention to the possibility of this injury in blunt injuries of the chest or abdomen. In the diagnostic part they describe the complex character of diagnosis of rupture of the diaphragm even when modern non-invasive examination methods are used, some of which (CT) may give false positive results. The authors describe typical symptoms leading to the diagnosis. PMID- 2603069 TI - [An unusual entrapment syndrome diagnosed early]. AB - The authors describe the case of a 32-year-old man with intermittent claudications. Large abnormal muscular structures were found in the popliteal regions, incl. a secondary pterygium on the right. On both limbs these muscles arrested by their pressure during contraction the blood flow in the popliteal artery and caused its temporary lateral deviation. The described sings (abnormally large muscles, pterygium, deviation to the their side) differentiate this entrapment syndrome from known patterns of the latter. The syndrome was diagnosed in time before the artery was morphologically altered. The surgical treatment involved an extensive resection of the abnormal muscles and revision of the artery. PMID- 2603070 TI - [Isolated aneurysm of the iliac artery as a source of postoperative peripheral embolism]. AB - An isolated aneurysm of the iliac artery is a rare disease occurring 10 times less frequently than an aneurysm of the aorta. Aneurysms of the iliac artery are yet 10 times less frequent. The rare incidence of the condition is the cause why it is not taken into account in the differential diagnosis. Electively treated aneurysms have a minimal mortality and morbidity, while symptomatic aneurysms with subsequent complications due to haemorrhage, penetration or embolization calling for urgent surgery, have a mortality of cca 50%. In the patient described by the authors embolization and ischaemia of the lower extremity developed during the immediate postoperative period after prostatectomy. Only the peroperative finding explained the cause of the embolization. PMID- 2603071 TI - [Volvulus of the appendix]. AB - The authors describe the case-history of a volvulus of the appendix which developed as a result of an inborn defect in the appendiceal mesenteriolume. The surgical finding did not suggest primary appendicitis but rather strangulation of the aboral part of the appendix. PMID- 2603072 TI - [Inflammatory aneurysm of the pelvic artery]. AB - The authors describe an uncommon case of an inflammatory aneurysm of the common abdominal aorta which was successfully treated by resection and prosthesis. In the discussion the authors deal with the specific features of this type of aneurysm, as compared with common sclerotic ones. They recommend the best diagnostic procedure, surgical approach and postoperative treatment. PMID- 2603073 TI - [Present possibilities of surgical treatment of chronic pancreatitis]. AB - The author gives an account of his experience with 54 operations in the algic form of chronic pancreatitis in 1982-1986. Based on examination of patients by modern visualization methods of the pancreas (USG, CT, ERCP), the ductal or parenchymatous form of chronic pancreatitis was diagnosed. In the ductal form of chronic pancreatitis (enlarged pancreatic duct) drainage operations were performed in 43 patients (pancreatojejunostomy in 24 patients and cystogastrostomy in 19 patients). In the parenchymatous form (a senotic pancreatic duct) resections were made (distal resection duodenopancreatectomy and 95% - pancreatectomies). Check-up examinations 1-5 years after operation revealed disappearance of pain in 90% of the patients. PMID- 2603074 TI - [Aneurysm of the hepatic artery]. AB - Aneurysms of the hepatic artery are a very rare disease. The authors describe the symptomatology, most frequent localization, diagnostic methods and possibilities of surgical treatment. PMID- 2603075 TI - [Primary malignant tumors of the gallbladder]. AB - The author analyzes 33 cases of malignant tumours of the gallbladder in the course of 10 years from the diagnostic, therapeutic and prognostic aspect with regard to possibilities of type II hospitals. PMID- 2603076 TI - [Perineal infiltrates after amputation procedures in carcinoma of the rectum]. AB - The authors present their experience with perineal infiltrates amputations on account of rectal carcinoma. In the course of 1986 in the Oncological Research Institute in Brno 58 patients with this diagnosis were hospitalized. After amputations three types of surgical complications were observed: 1. early inflammatory infiltrations, 2. late abscesses and 3. locoregional relapses of the primary tumour. Local relapses were detected first after five months and not later than three years after the radical operation. The authors draw attention to the fact that the first manifestation of the locoregional progress of the disease was a sensation of pressure or pain, which preceded the development of a resistance on the perineum and fever. The extent of tumourous infiltration was assessed by computed tomography. Reduction of locoregional relapses depends according to authors above all on a comprehensive approach to treatment. The usefulness of adjuvant irradiation is obvious. The authors assume that it is important to decide whether to irradiate before or after operation or to combine both methods and whether too combine irradiation with chemotherapy. Due to difficulties of therapeutic influencing of local relapses they emphasize above all the demand of respecting the rules of oncological surgery during the first operation. PMID- 2603077 TI - [A technic for radical subcutaneous fasciotomy of the leg]. AB - At the surgical department of District Institute of National Health in Prostejov in 1984-1986 eight subcutaneous fasciotomies were performed after embolectomies with prolonged is haemia. The surgical technique was standardized and its safety was proved on 20 lower limbs of corpses. For the implementation a special instrument is needed--a fasciotome made from a Kuntschner nail. For reliable decompression of all four osteofascial spaces of the leg it is sufficient to make a 50 mm long transverse incision, about 30 mm proximally from the apex of the external ankle. Local anesthesia of the extent of the skin incision is sufficient, the fasciotomy itself is not painful. Due to its rapid and unpretentious character the procedure is suitable in postischaemic syndrome or a prophylactic operation. PMID- 2603079 TI - Problem buildings: building-associated illness and the sick building syndrome. PMID- 2603078 TI - [Surgery for gastroduodenal ulcer in Czechoslovakia in 1985]. AB - The authors submit statistical information on the morbidity from gastroduodenal ulcers in surgical departments in the CSR in 1985. These are the first report of this type; unfortunately they are not yet complete as far as partial diagnoses are concerned, as sometimes doctors use only three-digit codes when filing in the forms. The total number of gastroduodenal ulcers accounts for 2% of all hospitalized patients in surgical departments on the CSR and only 41.4% are operated. It seems that to surgical departments still many patients are referred directly who were not examined by a specialist in internal medicine or by a gastroenterologist. Interregional differences are considerable. Gastric ulcers are more numerous, 1632, as compared with 1464 duodenal ulcers. The position is similar as regards perforated ulcers or ulcers with acute haemorrhage. There are also differences in the mean treatment period. It is somewhat longer in duodenal ulcers in all groups. On the other hand, the lethality is lower in duodenal ulcers in general as well as after perforation and haemorrhage. The development of urgent surgery in perforated ulcers in a long-term comparison does not disclose any obvious improvement. Therefore the question of prevention by early operation of gastroduodenal ulcers before complications develop is even more important. PMID- 2603080 TI - [Electrochemical stability of dental materials. Part 4. Immersion test of amalgam]. AB - Specimens prepared with three commercial dental amalgams were immersed in three kinds of solutions: Ringer's, 1% lactic acid and 0.05% hydrochloric acid, at 37 degrees C, and subjected to a repeated corrosion test for fifteen weeks. Quantitative analysis was performed by inductively coupled plasma emission spectrometry for released metal elements to determine the composition of these amalgam alloy powders and immersed specimens. The immersion test for one week was not sufficient to prove the corrosion tendency of amalgam and a longer period of immersion was considered necessary. The kinds and amounts of released elements in each solution differed, and the corrosion tendency of high copper amalgam differed from that of conventional amalgam. PMID- 2603081 TI - [Pre-treatment of dental alloy for adhesive restorations. Part 3. Alkyl ammonium/Sn composite plating to various dental alloys]. AB - The effect of alkyl ammonium salt/Sn composite plating on the adhesive characteristics of dental alloys was examined. The surface of dental alloys, on which such a composite plating was made, was analyzed by ESCA. The effect of the length of alkyl chain and its terminal atomic groups on the tensile adhesive strength to an adhesive resin was also examined. ESCA analysis revealed that both C and N atoms from the alkyl ammonium salts were certified on the surface of the dental alloys. Stable tensile adhesive strength, as high as 500 kg/cm2, was obtained when the number of C atoms of alkyl chain was 10 to 16. The alkyl ammonium salts containing such groups as hydroxyl, amino and vinyl at the terminal of the alkyl chain, were effective for increasing the tensile adhesive strength. PMID- 2603082 TI - [High strength Ag-Pd-Cu alloys]. AB - Twelve kinds of Ag-Pd-Cu alloy, containing 25, 30, 35, 40 wt% Pd, 20, 25, 30 wt% Cu and the residual quantity 30-55 wt% Ag were melted in an argon atmosphere. These alloys were cast using dental precision casting, subsequently, softening heat treatment (water quenching from 800 degrees C) and hardening heat treatment (450-250 degrees C oven cooling) were applied. After softening heat treatment, the Vickers hardness, tensile strength, and elongation of the experimental alloys ranged from 145 to 200, from 41 to 60 kgf/mm2 and from 11 to 27%, respectively. Therefore, these alloys were very ductile in softening heat treatment condition. After hardening heat treatment, the Vickers hardness of the alloys increased in the range of 241-433 and tensile strength increased in the range of 73-107 kgf/mm2. However, elongation decreased to 0.5-3.5%. Composition of the alloy that had the maximum tensile strength (104 kgf/mm2) was about 45 Ag-35 Pd-20 Cu. Brightness (L*) of the test pieces that were immersed in 0.1% sodium sulfide solution of 37 degrees C for 3 days ranged from 58 to 67. After hardening heat treatment, the Ag-Pd-Cu ternary alloy containing 20-30% Cu, 30-40% Pd had satisfactory high hardness and strength for adhesion bridge, but their elongation and tarnishing resistance were insufficient for clinical application. PMID- 2603083 TI - [Mechanical properties of wiredrawn Ag-Pd-Cu alloys]. AB - Nine experimental Ag-Pd-Cu ternary alloys, containing 20-30 wt% Pd and 10-20 wt% Cu, were cast into rods 4.5 mm in diameter using an original vacuum/argon pressure oxide-free casting technique. Test samples 2.0 mm in diameter were made from the rods by wire-drawing. After softening and hardening heat treatments, mechanical properties (modulus of elasticity, elastic limit, proof stress, tensile strength, elongation, and Vickers hardness) of the samples were measured to analyze the effects of composition and fifteen sets of correlations between the mechanical properties on the condition that few internal casting defects existed. After softening heat treatment, values of hardness and strength increased with increasing Cu and Pd contents, while they increased approximately with increasing Pd content after hardening heat treatment. After softening and hardening heat treatments, tensile strength ranged from 44.4 to 60.7 and from 68.1 to 89.1 kgf/mm2, respectively. Values of elongation were more than 10% even after hardening heat treatment. Fourteen out of fifteen correlation coefficients (r) were statistically significant (p less than 0.01). One of the regression lines derived was as follows. Tensile strength (kgf/mm2) = 9.1 +/- 0.305 Hv (r = 0.990) Moreover, the mechanical properties observed in this investigation were compared with those of ordinarily cast samples with the same compositions. PMID- 2603084 TI - [Superplastic forming of titanium alloy denture base]. AB - Ti-6Al-4V alloy has both excellent biocompatibility and superior mechanical properties. This Ti-6Al-4V can be deformed greatly and easily at the superplastic temperature of 800 degrees C to 900 degrees C. The superplastic forming of Ti-6Al 4V was made to apply to fabrication of denture base. Almost the same procedure as for dental casting mold was employed in producing the superplastic forming die by the improved phosphate bonded investment. In the pressure vessel of heat resistant alloy, Ti-6Al-4V plate was formed superplastically on the die by argon gas pressure at 850 degrees C. The fit of superplactic forming Ti-6Al-4V denture base was better than that of casting Co-Cr alloy denture bases. The Ti-6Al-4V alloy might react a little with the die. Because micro Vikers hardness of the cross-section did not go up too much near the surfaces. Even just after being formed, the surfaces were much smoother than that of Co-Cr alloy casting. The tensile strength and yield strength of superplastic forming Ti-6Al-4V were higher than those of Co-Cr castings. The elongation was about 10%. These results show that superplastic forming of Ti-6Al-4V would be suitable for a denture base. PMID- 2603085 TI - [Three dimensional shape measurement of teeth (Part 2). The accuracy of the three dimensional measurement using a laser displacement meter]. AB - The three dimensional shape measurement system of teeth was improved. The system was assembled by using a high precision laser displacement meter and computer controlled scanning machine (CAMM-3). At the fissure of the occlusal plane, the abnormal data caused by multiple scattering of the reflected beam were observed, but they were dissolved by painting the stone model teeth gray and measured by using a laser displacement meter of MD-40 type with a short measurement length. Another error observed when the reflected beam was shielded by the model tooth itself, was corrected by connecting some data which were measured by rotating the teeth model on the gonio stage. A software program was composed to connect the data. The accuracy of measurement of this system was examined on the slope of a 7 abutment tooth. When the model teeth were measured without tilting, the difference between the true value and the measured value was -240 microns ( 2.8%). However, by tilting the model teeth +/- 20 degrees on the gonio stage and connecting a couple of data obtained with two tilting angles by means of the software program, the difference was considerably decreased into + 10 microns and the accuracy was + 0.1%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2603086 TI - [Finishing and polishing of composite resins. The experimentally designed silicone cup hards and their polishing ability]. AB - To establish the most efficient polishing technique for composite resins, four kinds of silicone cup hards were experimentally designed, and the surface texture of two semihybrid composite resins polished with these experimental polishing tools were examined using a surface roughness recorder and by SEM. The individual silicone cup hard consisted of a hard rubber and silicone carbide abrasive particles being sized into #180 (P0), #360 (P2), #600 (P3), and #2500 (P4), respectively. Combination polishing with both P3 and P4, as well as from P0 through P4 in this order, efficiently created the smoothest surfaces for the semihybrid composite resins, which are generally considered to be hard to polish in the routine clinic. PMID- 2603087 TI - [Molecular composite resins reinforced with polyaramides (Part 1). Molecular interaction between N-Octylated-Poly-p-Phenylene Terephthalamide (PPTA) as core molecule and PMMA and Polystyrene (PS) as matrices]. AB - Molecular composite PMMA resin (Oct-PPTA-PMMA) can be reinforced with poly-N octyl-p-phenylene terephthalamide (Oct-PPTA) as rigid core molecule. Compounding 3 wt% of Oct-PPTA to PMMA increased compressive, diametral and bending strength by 10 to 15%. The molecular interaction between Oct-PPTA as the core molecule and PMMA as a polar matrix and polystyrene (PS) as a non-polar matrix was examined with respect to dynamic viscoelasticity. Compounding 3 wt% of Oct-PPTA (Oct-PPTA PS) to PS decreased compressive, diametral and bending strength by 15 to 30%. The dynamic storage modulus (G') value of Oct-PPTA-PS is lower than G' of PS in the region from rubbery state to viscous flow state. These results reveal a significant effect of the polar groups on the molecular interaction between the core molecule and matrices in the molecular composites compounding Oct-PPTA as core molecule. PMID- 2603088 TI - [Mechanical properties and phase transformation of super-elastic Ni-Ti alloy wires. Part 1: Relation between super-elasticity and phase transformation]. AB - The relationship between mechanical properties and thermal behavior of super elastic Ni-Ti alloy orthodontic wires was investigated in order to use them effectively in clinics. Three types of super-elastic Ni-Ti alloy orthodontic wires, SENTALLOY-BLUE(SB), YELLOW(SY) and RED(SR), were used. Two parameters were introduced from the load-deflection curves in three point bending test to evaluate their mechanical properties. One was the super-elastic index (SEI) for super-elasticity, and the other was the E-load for the load in the super-elastic region. Their thermal behavior in the course of the transformation analyzed with DSC, and compared with the mechanical properties. The specimens heat-treated at 500 degrees C for 30 min were also examined. The differences in mechanical properties of the super-elastic Ni-Ti alloy orthodontic wires used in this study were thought to be more affected by the height of the thermic peak and the form of the DSC curves than the transformation temperature. The higher the thermic peak, the higher tended to be the SEI and the lower E-load. To the contrary, the lower thermic peak, the higher was the E-load and the lower was the SEI, and the continuous force could not be achieved. The remaining work-hardened structure was thought to influence these differences. PMID- 2603089 TI - [Mechanical properties and phase transformation of super-elastic Ni-Ti alloy wires. Part 2: Changes of properties through heat treatment]. AB - Three types of super-elastic Ni-Ti alloy orthodontic wires, SENTALLOY-BLUE (SB), YELLOW (SY) and RED (SR), on the change of properties were studied especially the reversible change of the load level, using three point bending test and DSC. The heat treatment at 440 degrees C caused the largest reduction in mechanical properties of SB and SY, and the 400 degrees C treatment did that of SR. The load level of SR was less changeable than those of SB and SY by the difference of heat treatment temperature. Mechanical properties of SY were almost reversible by the alternate heat treatment at 440 degrees C and 510 degrees C. Then the 440 degrees C-heat treatment increased the transformation temperature, and the 510 degrees C heat treatment decreased them. The variation of the mechanical properties completely corresponded to the change in transformation temperature. The variation appears to result from some internal structure changes. Changes in mechanical properties are observed by heat treatment at 360, 400 and 480 degrees C, but the reversibilities were not so clear. The change of the properties of super-elastic wires are influenced by the kind of wire and the heat treatment condition. The reversible change in the mechanical properties seems to have many advantages over super-elastic Ni-Ti alloy orthodontic wires. PMID- 2603090 TI - [Bone inductive activity of bone morphogenetic protein combined to beta tricalcium phosphate]. AB - For the development of a new delivery system for bone morphogenetic protein (BMP), BMP was bound to beta-tricalcium phosphate (beta-TCP). Powder beta-TCP was synthesized from calcium hydrogenphosphate and calcium carbonate by the dry process method to make the best use of the advantages of the BMP, which show good bone inductive activity on the surface and enhancement of new tissue by reducing the area that the implant material occupies. The beta-TCP + BMP complex and beta TCP for the controls only were implanted in the muscle pouches of mice. Three weeks later new bone formation was observed on the exterior surface of beta-TCP + BMP complex but not of beta-TCP controls. The bone inductive activity of the beta TCP + BMP complex is better than the BMP alone. The histological relation between the original tissue and the newly induced bone formation was normal and that of new bone and beta-TCP was also good. Consequently, the beta-TCP + BMP complex has good histocompatibility when implanted. PMID- 2603091 TI - [Effects of Co, Mo and Cu on the fluidity of 80Ni-20Cr alloy]. AB - An attempt was made to determine the castability of Nickel-Chromium alloys which contained an additional element. 80 Ni-20 Cr binary alloy was prepared in the argon atmosphere and saved as control alloy. Then three sets of different components alloys, each set contains different composition (5, 10, 15%) of Co, Mo, or Cu to the control alloy, were prepared and used as test materials. The fluidity was evaluated by casting them into the cylindrical coil shaped mould cavity and examining their ability to flow into the mould cavity before solidification took place. The fluidity of Nickel-Chromium alloy was not changed by addition of Co or Mo up to 5%. However, the fluidity was significantly decreased by addition of Cu, or Mo when its concentration was increased over 5%. Thus, from the viewpoint of castability a large amount of Mo or Cu should not added to the Nickel-Chromium alloy. PMID- 2603093 TI - [Crystal growth on human dentin surface]. AB - Gypsum crystal growth on human dentin surface was investigated using a crystal growth agent composed of 4-20% ammonium sulfate and 5-60% acrylic acid aqueous admixtures. In the treatment with 4% ammonium sulfate which contains the concentration of acrylic acid from 5% to 60%, fine half-spherical aggregates of 25 microns in diameter of needle-like crystals were obtained from 35% acrylic acid and large ones from 30% acrylic acid. Using the crystal growth agent of 4% ammonium sulfate-35% acrylic acid aqueous admixture, the human dentin surface pretreated with sulfates of different cations was evaluated from crystal growth. All sulfates without 4% ZnSO4 formed half-spherical aggregates of needle-like crystals. Diameter of their half-spherical aggregates increased as follows; 4% Na2SO4 less than none-treatment less than saturated CaSO4.2H2O less than 4% K2SO4 less than 4% MgSO4 less than 4% ZnSO4. The half-spherical aggregates from sulfates of Na+ and K+ (alkali metal) grew finer than those from sulfates of Ca2+ and Mg2+ (alkali-earth metal) and Zn2+ (zinc) and their area on dentin surface increased more with sulfates of alkali metal than with those of alkali-earth. PMID- 2603092 TI - [Chemical durability of composite resins]. AB - To evaluate their chemical durability, samples of posterior composite resins were stored in NaOH (0.1 mol, 1 mol), HCl (0.1 mol, 1 mol), acetone (99%), and distilled water at 37 degrees C for a week and subjected to the direct tensile test, measurement of surface roughness and SEM observation. NaOH caused the degradation of composite resins, decrease of tensile strength and increase of surface roughness. The SEM photograph of fractured surface of tensile specimens revealed the degradation zone under the surface. It was considered that NaOH caused the hydrolysis of silan coupling of composite resins. HCl also caused the degradation of composite resins, but some resins showed the durability in this condition. More examination is needed to clarify the mechanism of degradation. Acetone caused the degradation of matrix resin and some composite resins. It was considered to dissolve the low degree of polymerized matrix resin of composite resins. Immersion in chemicals of composite resins was thought to be useful to evaluate the chemical durability and to accelerate the degradation in water. PMID- 2603094 TI - [Influence of tannic acid on physical and chemical properties of alpha-tricalcium phosphate-citric acid-tannic acid complex]. AB - A mixture of alpha-tricalcium phosphate [alpha-Ca3(PO4)2; alpha-TCP] with a citric acid solution produces a hardened alpha-TCP-citric acid complex. The influence of tannic acid as an additive in the solution on the physical and chemical properties of the obtained complex was examined as a basic study for new calcium phosphate materials incorporating alpha-TCP. alpha-TCP was mixed with mixing liquids containing citric and tannic acids at various ratios [total acid = 45% (w/w)] at a powder/liquid = 2.2/1.0 (g/g). Compressive strength, setting time, and solubility & disintegration of the resulting complexes were measured by the methods specified by ADAS No. 61. After immersing the plates of the complexes in distilled water for 1 and 7 days, the surface structure of the plates was examined by using X-ray diffraction, scanning electron microscopy and IR spectroscopy. The substances solubilized and disintegrated in the water for 1 day were also examined by measuring quantitative Ca and P concentration. When the ratio of tannic acid to total acids (T/A) was higher than 30% (w/w), both setting time and solubility & disintegration increased remarkably. In the case of the complex at T/A = 30%, both setting time and solubility & disintegration showed the minimum value (6.25 min and 1.70%). For compressive strength, the maximum value (139 MPa) was obtained at T/A = 10%. Although the strength decreased markedly with increasing T/A beyond 10%, that of the complex at T/A = 30% was still a high level (103 MPa). The products on the surfaces before and after immersing the plates in distilled water were also discussed. PMID- 2603095 TI - [AE characteristics during compression test of high-copper amalgams and visible light-cured composite resins]. AB - Differences in environmental strength of high-copper amalgams and photo-cured composite resins for posterior after storage in deionized water at 37 degrees C for 1 year were evaluated by examining compressive strength and acoustic emission (AE) characteristics. The results were as follows: Microfailure in amalgams and composite resins was detected from the onset of stress and their microfailures toward catastrophic failure occurred at 70 to 90% of their ultimate strength. One year compressive strength for amalgam decreased to 80 to 98% of its 24-hour compressive strength and that for composite resin to 65 to 75%. PMID- 2603096 TI - [Effect of loading time on the Vickers hardness number of dental gold alloys]. AB - The Vickers hardness number (VHN) of pure metals (tin, aluminum, copper and gold) and dental gold alloys was measured using an automatically indenting and reading Vickers hardness tester (AKASHI.AUTOVICK) under a load of 1,000 gf with different loading times of 5 to 55 seconds. The samples of pure metals were cold rolled and softened by heating above recrystallization temperatures. The samples of ADAS No. 5 gold casting alloys were cold rolled, and then subjected to a softening heat treatment by water quenching (Types I, II, III and IV) or a hardening heat treatment by 450-250 degrees C/30 min oven cooling (Types III and IV). The results showed that there were no statistically significant differences between the measured values of VHN of a sample with different loading times as for the metals studied except pure tin which had a VHN of 5-6. The measured values of VHN by AUTOVICK were affected by the brightness of a light source for measurement, and they increased by 1.1 approximately as the voltage of the light source increased by 0.1 V. This was considered to be due to the protuberance caused by plastic flow of metals or slip lines on the surface around the indentation. PMID- 2603097 TI - [Clomiphene]. PMID- 2603098 TI - [The role of nurse midwives in the labor room]. PMID- 2603099 TI - [The role of the obstetrician in the labor room]. PMID- 2603100 TI - [The role of the pediatrician in the birthing room]. PMID- 2603101 TI - [Normal delivery in the vertex presentation]. PMID- 2603102 TI - [Other methods of delivery]. PMID- 2603103 TI - [The forceps]. PMID- 2603104 TI - [Normal and pathological delivery]. PMID- 2603105 TI - [Role and job description of the nurse in emergencies]. PMID- 2603106 TI - [The role of the nurse in the labor room]. PMID- 2603107 TI - [Anorexia in the child and the adolescent]. PMID- 2603109 TI - [Inflammatory and infectious lesions of the uterine cervix]. PMID- 2603108 TI - [Trichomonacides]. PMID- 2603112 TI - [Surgery of the uterine cervix. Role of the operating room nurse]. PMID- 2603111 TI - [Cancer of the uterine cervix]. PMID- 2603110 TI - [Condylomata, papillomaviruses]. PMID- 2603113 TI - [Communal education. The Kibbutzim of Israel]. PMID- 2603114 TI - [Anatomy, physiology and diagnostic methods of the uterine cervix]. PMID- 2603115 TI - [Autonomy, what it gains]. PMID- 2603116 TI - [Drawing, an adventure for the child]. PMID- 2603117 TI - [Tumors of the uterine cervix. Anatomo-pathological aspects]. PMID- 2603118 TI - [Intracavitary high-dose-rate-afterloading-radiotherapy in the esophagus of the pig]. AB - The tolerance of sound esophageal mucosa to intracavitary high dose rate afterloading contact therapy with unique doses of 6 Gy and 12 Gy, respectively, was investigated in 15 pigs. Whereas no macroscopic or microscopic alterations of the mucosa are found after 6 Gy, a unique application of 12 Gy produces most severe side effects such as vascular occlusion due to fibrosis of the intima, formation of fistulas, and perforations of the esophagus wall. Future investigations will have to aim at the elaboration of schemes for dosage and fractionation. PMID- 2603119 TI - [Prophylactic irradiation of blood components with conventional radiotherapy devices]. AB - The irradiation of blood components is supposed to be the safest way of the graft versus host reaction prophylaxis. The radiotherapy facilities and compact irradiators for blood preparations and biological materials are used for prophylactic irradiations, practically. The radiotherapy machines allow a homogeneous dose application, but need a high organizing effort. The use of compact irradiators is less complicated but the large dose differences can be found in the target volume. There is no agreement about the extent of the prophylactic dose. For radiation biology reasons the application of prophylactic doses between 15 and 50 Gy seems to be justified. A restriction of this range in favor of higher doses can be expected, when newer experimental findings are proven by clinical observations. PMID- 2603120 TI - Reactions of isolated rat aorta to X-irradiation. AB - The reaction of isolated helical strips of rat aorta to X-irradiation was studied: X-rays (50 kV) induced a reproducible, reversible contractile response at threshold doses of 2.5 Gy (60 Gy/min) and 10 Gy (30 Gy/min). After repeated irradiation with the same doses at equal time intervals and constant dose-rate (for example 50 Gy every 15 min, dose-rate 60 Gy/min) the contractile response was progressively diminished, i.e. a tachyphylaxis appeared. The preparations still reacted even after total doses over 1000 Gy. The X-ray induced contractile responses were dose- and dose-rate dependent. Quantitative analysis indicated no essential differences in the radiation-induced contractile response when recorded under isometric or isotonic conditions. After hypothermia (20 degrees C) or hyperthermia (42 degrees C) no visible radiation response could be induced. Part of the aortic strips were spontaneously active: X-ray doses of 5 to 10 Gy stimulated, while doses of 100 to 200 Gy inhibited or blocked the spontaneous phasic activity. A comparison between the immediate X-ray reaction of vascular and non-vascular smooth muscle preparations is given. Participation of cholinergic and adrenergic mechanisms in the X-ray induced contractions of rat aorta seems to be ruled out, because the blocking agents atropine, phentolamine, and bretylium had no effect. PMID- 2603121 TI - Glucose-6-phosphate dehydrogenase activity in CaNT tumours of different volume and response to tumour clamping and X-irradiation. AB - Changes in the levels of glucose-6-phosphate dehydrogenase (G6P-DH) activity, versus tumour volume were measured in vivo under normoxic conditions in the CaNT tumours grown in CBA mice. A monotonically increasing relation was found. Artificially induced tumour hypoxia resulting from 15 min of clamping was accompanied by enhanced G6P-DH activity, but one hour after release of the clamps (reflow), the specific activity of the enzyme decreased to about the same level as that of the normoxic controls. Also the levels of G6P-DH activity in normoxia were measured one hour after 5, 10 and 15 Gy of X-rays (100 kVp). A significantly higher G6P-DH activity which increased with dose, was found in the tumours. This paper gives evidence of increased G6P-DH activity linked with tumour progression, under gradual amplification of the metabolic unbalance. The augmentation of G6P DH following X-irradiation probably represents a cellular adaptive defence mechanism during the demand for increased metabolism. PMID- 2603122 TI - Radiosensitivity of drug-resistant human tumour xenografts. AB - The radiosensitivity of three drug-resistant sublines of a human epidermoid lung carcinoma growing as xenografts in nude mice was investigated. Drug resistance to vincristine, actinomycin D and cisplatin was developed in vivo by repeated drug treatment. It was found that all three drug-resistant tumour lines were not cross resistant to irradiation. PMID- 2603123 TI - Computer simulation of clinical irradiation schemes applied to in vitro tumor spheroids. AB - In this contribution the attempt is made to study the effect of irradiation on in vitro tumor spheroids by computer simulation applying clinical treatment schedules. The starting point is a computer model stimulating the spatial (three dimensional) growth of a tumor spheroid, developed by our group previously. In the present paper, this model is extended by creating a comfortable data input with a graphical interface. This expansion includes characteristic features of radiotherapy (sensitivity, repair capacity, reoxygenation, repopulation) and therapy schedules. In this way, it is possible to test different clinical irradiation schemes on in vitro tumor spheroids by computer experiments (standard and non-standard fractionations). In the long run the aim of our work is to optimize irradiation schedules by computer simulation prior to clinical therapy. PMID- 2603124 TI - Symposium of the European Clinical Neutron Dosimetry Group (ECNEU). Essen, October 27, 1988. Abstracts. PMID- 2603125 TI - Class I and II composite resin restorations: 4-year clinical follow up. AB - The clinical properties and longevity of two posterior composite materials were studied during a 4-year period. 137 Class I and II restorations in 65 patients were evaluated directly using USPHS criteria. Araldite casts were used to categorize quantitatively the amount of occlusal wear according to the Leinfelder method. No differences could be found between the two materials regarding clinical properties and failure rate. The overall success rate was high (84%). The average occlusal deterioration after 4 years was about 140 microns. PMID- 2603126 TI - Intraalveolar transplantation of teeth. IV. Endodontic considerations. AB - Twenty-six teeth with crown-root fractures have been subjected to intraalveolar transplantation. In 13 teeth the endodontic treatment was instituted before transplantation and in another 13 teeth 3-4 weeks after transplantation. Bacteriological tests showed that endodontic treatment after transplantation was preferable with statistically fewer treatments and more reliable results. The results thus points in favour of a late endodontic treatment with controlled aseptic conditions. PMID- 2603127 TI - Mercury accumulation in tissues from dental staff and controls in relation to exposure. AB - Samples, mainly from occipital cortex and pituitary gland, but also from rental cortex, olfactory bulbs, thyroid gland and liver were collected from autopsies of 8 dental staff cases and 27 controls. These samples were analysed for total mercury content using radiochemical neutron activation analyses. The results revealed high mercury concentrations (median 815, range 135-4,040 micrograms Hg/kg wet weight) in pituitaries from the dental staff cases compared to controls (N = 23, median 23 range 6-1, 170 micrograms Hg/kg). In occipital cortex, the cases had a median of 17, range of 4-300 micrograms Hg/kg and the controls (N = 20) had a median of 10, range 2-29 micrograms Hg/kg. A few samples from olfactory bulbs show low mercury concentrations for both cases and controls. Renal cortex was analysed from three cases and contained clearly higher concentrations (945, 1,545, 2,110 micrograms Hg/kg) compared to controls (N = 12, median 180, range 21 810 micrograms Hg/kg). There is no control material for the other analysed samples, but one thyroid sample had an extremely high concentration of 28,000 micrograms Hg/kg. PMID- 2603128 TI - Relationship between oral symptoms, salivary function, smoking habits and general health in patients with complaints related to dental restorative materials. AB - Eighty consecutive patients, referred to the Department of Prosthetic Dentistry, Public Dental Service, Stockholm, for examination of complaints related to dental restorative materials or for supposed adverse effects from mercury released from dental amalgams were investigated. Clinical examination as well as battery of laboratory tests were performed. Statistical correlations were found between subjective and objective oral symptoms and lowered pH-values in stimulated saliva (p less than 0.001) as well as between objective oral symptoms only and lowered pH-values in stimulated saliva (p less than 0.001), which indicate salivary tests to be a useful tool when examining this type of patients. PMID- 2603129 TI - Dental health knowledge in a group of Latin American refugees in Sweden. AB - Sixty-nine Latin American refugees with a mean age of 31 years participated in this study. The knowledge about dental health before and after reading a self instructional manual in Spanish was tested by questionnaires. The test persons were also interviewed about their dietary habits. The results showed an improvement of 30% of right answers after reading the manual and that a frequent sugar consumption was common. This indicates that a self-instructional manual can be of value in oral health prevention in a similar group of non-resident immigrants. PMID- 2603130 TI - Developing solutions for dental X-ray processors. AB - Six developing solutions suitable for automatic X-ray processors with high developer temperature have been tested during a period of 14 days without replenishment of the chemicals. The results are presented as blackening of dental test films with an image of an aluminium step wedge (penetrometer). Both speed and contrast could be measured in this manner. Freshly mixed solutions showed marked differences in processing of films where the developers Durr, Readymatic (Kodak) and Tetenal (Mediquipe) were best. After 14 days in the processor, the developing effect was poor for most of the tested liquids, due to atmospheric oxidation. The best images, with the least radiation, will be obtained with freshly mixed chemicals suitable for the films used. Besides a lower radiation dose to the patient, due to a short exposure time, blurring caused by the patient's moving will be reduced. Other factors such as the pack and prices must also be taken into consideration in the choice of radiographic solutions. PMID- 2603131 TI - Surface changes on dental materials. The influence of two different dentifrices on surface roughness measured by laser reflexion and profilometer techniques. AB - Surface changes and wear resistance were investigated on eight different dental materials, using a laser reflexion technique and a profilometer. The tested materials were: (table; see text) The materials were subjected to brushing in a brushing machine, containing a toothpaste-water slurry. Two different toothpastes were used separately; Clinomyn and Colgate. The results showed that all the materials were to some extent affected by the brushing. Titanium was the most and SR Isosit N the least wear resistant material. Clinomyn and Colgate influenced the materials in different ways depending on their abrasive properties. PMID- 2603132 TI - [Infection and fear]. PMID- 2603133 TI - [No to shortened nursing education]. PMID- 2603134 TI - [Information booklet for rheumatism patients]. PMID- 2603135 TI - [HIV-infected patients with acting-out behavior]. PMID- 2603136 TI - [Strike--support to nurses in Tromso]. PMID- 2603137 TI - ["Case 1919 Miriam Bergholz"--toward a solution?]. PMID- 2603138 TI - [Work in care for the aged. Career image and professional adjustment. A study of a nursing choice in health services for the aged]. PMID- 2603139 TI - [Nurses and HIV infection. Are attitude and behavior in line with our knowledge?]. PMID- 2603140 TI - [Psychiatric nursing. The meaning of trust in a therapeutic community]. PMID- 2603141 TI - [Education. Social subjects in nursing college]. PMID- 2603142 TI - [Work in care for the aged. Career picture and professional adjustment (II)]. PMID- 2603143 TI - [Flexible retirement age for the professionally active]. PMID- 2603144 TI - [Foreign cultures. When a 'departed one' steals away--on cultural conflict in nursing. Interview by Kari Holthe]. PMID- 2603145 TI - [Stroke--the left side of your life has disappeared...]. PMID- 2603146 TI - Dopamine agonists at repeated "autoreceptor-selective" doses: effects upon the sensitivity of A10 dopamine autoreceptors. AB - Previous reports have established the ability of dopamine (DA) agonists to stimulate inhibitory DA autoreceptors at doses which minimally stimulate postsynaptic DA receptors, suggesting that hyperactive DA transmission may be controlled clinically by treatment with DA agonists. Little is known, however, about the possible loss of autoreceptor sensitivity that may occur after repeated treatment with low doses of DA agonists. Extracellular single cell recording and microiontophoretic techniques were used to measure the sensitivity of impulse regulating DA autoreceptors on A10 DA cells in the ventral tegmental area (VTA) of chloral hydrate-anesthetized rats pretreated for seven days with repeated subcutaneous (s.c.) doses of the DA agonist apomorphine (APO). The ability of intravenous (i.v.) administration of the potent D2 DA agonist quinpirole (QUIN) to inhibit the firing of A10 cells was not attenuated in rats pretreated with repeated low doses (2 x 50 micrograms/kg/day, s.c.) of APO for 7 days, although higher doses (2 x 250 or 500 micrograms/kg/day) did cause subsensitive responses to QUIN. In rats pretreated with repeated low doses of APO, microiontophoretic application of DA on A10 cells revealed somewhat subsensitive responses. However, ibotenic acid lesions of postsynaptic cells in the nucleus accumbens (NAc) prior to initiation of APO treatment (2 x 50 micrograms/kg/day) did not alter the response of A10 cells to systemic QUIN, contradicting the possibility that the feedback projection from the NAc to the VTA was compensating for autoreceptor down-regulation during systemic challenge with QUIN. In contrast, administration of the irreversible DA antagonist EEDQ (2 mg/kg, i.p.) to control and APO-treated rats (2 x 50 micrograms/kg/day) 24 hr prior to recording did reveal a difference in A10 cell sensitivity to systemic QUIN and to microiontophoretic DA between the two groups, suggesting that "spare" DA autoreceptors may have concealed the down regulation of autoreceptors induced by repeated low doses of APO. Challenge of A10 DA cells with the partial DA autoreceptor agonist (-)-3-(3-hydroxyphenyl)-N-n propylpiperidine [(-)3-PPP], for which an autoreceptor reserve should not exist, produced slightly attenuated responses in APO-treated rats (2 x 50 micrograms/kg/day). These findings provide evidence for the existence of spare somatodendritic DA autoreceptors on A10 DA cells with respect to potent DA agonists, suggesting that repeated administration of "autoreceptor-selective" doses of DA agonists may not result in a diminished inhibition of DA neuronal activity. PMID- 2603147 TI - Changes in the structure of synaptic junctions during climbing fiber synaptogenesis. AB - Synaptogenesis between climbing fiber axons and Purkinje cells involves both an orderly translocation of synaptic junctions over the Purkinje cell surface and an elimination of all but one innervating axon. We used thin-section and freeze fracture electron microscopic techniques to study structural changes in synaptic junctions during this interval of synapse translocation and elimination. In freeze-fractured preparations, virtually all climbing fiber synaptic junctions with the perisomatic processes and somatic spines lacked the particle aggregates that characterized the extracellular half of the postsynaptic membrane of mature synaptic junctions with dendritic spines. Some climbing fiber junctions with the dendritic shaft in the second postnatal week were associated with such aggregates, despite the fact that these junctions are transient. Thus, during the interval when Purkinje cells initially were innervated by multiple climbing fibers, and subsequently denervated of all but one climbing fiber afferent per cell, only a few of the transient synaptic junctions on the cell body and proximal dendrites have associated particles. The presence of a particle aggregate at a synaptic junction does not appear to be correlated with the permanence of that junction and probably is not correlated with the capacity to support synaptic transmission. The particle aggregates might be indicative of relatively long-lived junctions, or might occur only at junctions formed by the climbing fiber that will persist in synaptic contact with the mature Purkinje cell. PMID- 2603148 TI - Excitatory amino acid treatment of the ventromedial globus pallidus enhances dopamine utilization in the prefrontal cortex of the rat via the thalamic mediodorsal nucleus. AB - Infusion of a low dose (5 microM) of the cell-selective chemical excitant quisqualic acid (QUIS) into rostral ventromedial globus pallidus (GP) had no immediate effect on DA utilization (assessed as [DOPAC]:[DA] and [HVA]:[DA] ratios) in either the medial bank of the prefrontal cortex (FCx) or the agranular insular cortex (AgCx). In contrast, a larger dose (630 microM) of another excitant sodium ibotenate (IBO) produced an immediate bilaterally symmetrical increase in both indices of DA utilization in FCx. There was also a marked trend towards a bilateral increase in these indices of DA utilization in AgCx. In order to determine whether these effects on cortical DA utilization are mediated by a direct cortical route or via the thalamic mediodorsal nucleus (lateral division, MDL), infusions of IBO into GP were repeated in animals with a 1-week-old N methyl-D-aspartate lesion of MDL. The increase in DA utilization of FCx following infusion of IBO into GP was abolished, although the trend towards increased DA utilization in AgCx was still maintained. Since MDL innervates FCx but not AgCx and since we have previously shown that MDL lesions alone have no effect on DA utilization in either cortical region, the present results suggest that the changes in cortical DA utilization are probably mediated via MD. Thus in addition to the well-documented control exerted by the thalamus over brain DA function, this has now been extended in the present study to include GP, which projects both directly and indirectly to the thalamus. PMID- 2603149 TI - Peripheral induction of burst firing in locus coeruleus neurons by nicotine mediated via excitatory amino acids. AB - The effect of systemic nicotine administration (50 micrograms kg-1 i.v.) on the activity of brain noradrenaline neurons in the locus coeruleus (LC) of chloral hydrate-anesthetized rats was analyzed with single cell recording techniques and quantitative computer assessment of firing rate, degree of bursting, and regularity of firing. Nicotine caused an increased firing rate of the cells, with an average time of onset of 1.7 s. An increase in burst activity was observed, as well as deregularization of the firing pattern. Intraventricularly administered kynurenic acid (1 mumol), an antagonist of excitatory amino acids (EAA), did not change the firing rate of the LC cells, but did induce a marked regularization of their firing pattern into a pacemaker-like activity and completely abolish burst firing. The EAA antagonist also blocked all of the above effects of nicotine on the LC neurons as well as their typical burst-activation response to a peripheral, noxious stimulus such as paw-pinch. Since the circulation time in the rat is about 20 s, these results provide unequivocal evidence for a peripheral site of origin for the rapid LC activation induced by systemic nicotine administration. The data also allow the conclusion that the nicotine-induced LC activation is indirect and dependent on EAA in brain. Our results provide evidence for a tonically active EAA input to the LC, being of importance for induction of changes in the spontaneous, pacemaker activity of LC neurons into burst firing or more irregular firing patterns. It is suggested that the LC activation by nicotine may be significant in relation to tobacco dependence. PMID- 2603150 TI - Human cortical neurons contain both nicotinic and muscarinic acetylcholine receptors: an immunocytochemical double-labeling study. AB - Using immunofluorescence histochemistry, in the human cerebral cortex neurons immunoreactive for both nicotinic and muscarinic acetylcholine receptor proteins could be demonstrated. Vibratome sections of biopsy and autopsy specimens of human temporal and occipital lobes were incubated with monoclonal antibodies specific for muscarinic (M 35) and nicotinic (WF 6) acetylcholine receptor protein. Immunoreactive sites were visualized using a biotin-streptavidin phycoerythrin system (M 35, red fluorescence) and fluorescein-conjugated immunoglobulins (WF 6, green fluorescence). Immunofluorescence of both antibodies was preponderant in pyramidal neurons located in layers II/III and V and their apical dendrites. Some round and ovoid immunolabeled cells were encountered in layers VI and IV. About 30% of the cholinoceptive cortical neurons, in particular the pyramidal cells, displayed immunoreactivity for both receptor types. The present investigation shows a subpopulation of human cortical neurons to contain both nicotinic and muscarinic receptors. The coexistence of acetylcholine receptors may provide the morphological basis of simultaneous impact of acetylcholine on both receptor types in the same neuron of the human cerebral cortex. PMID- 2603151 TI - Cocaine receptors: in vivo labeling with 3H-(-)cocaine, 3H-WIN 35,065-2, and 3H WIN 35,428. PMID- 2603152 TI - Professional organization of physicians: balancing the cost-quality equation. An introduction. PMID- 2603153 TI - The demand for effectiveness, efficiency and equity of health care. AB - Effectiveness, efficiency and equity in health care are discussed in this article against the background of concerns that 'cost containment' may lead to reductions in quality of care. It is suggested that effectiveness is best seen from the patient's point of view and that it relates to more than simply improved health status. Efficiency and equity are better viewed from a societal stance. The paper discusses the role of the medical profession in effectiveness, efficiency and equity and argues that the role of medical doctors needs to be constrained. PMID- 2603154 TI - Quality of care and cost containment in the U.S. and U.K. AB - Many activities of doctors in the acute hospital sector do not improve patient outcome because they are inappropriate. Curtailing interventions that are unnecessary (because the patient is not bad enough) or are unsuccessful (because the condition is too advanced) could both save resources and improve care. Rational rationing depends on knowledge about the expected benefits of various technologies when used in different clinical circumstances. PMID- 2603155 TI - Medicine as a career: choices and consequences. AB - Medicine has traditionally been regarded as a rewarding career both financially and socially. How true, however, is that tradition in today's world of rising costs and decreasing revenues? The educational debt of the physician-in-training is steadily increasing, and currently does not affect specialty choice. As the cost of medical education continues to rise, the applicant pool begins to shrink, thereby possibly affecting the quality of future physicians. Once the physician has completed training however, the majority enjoy a positive return on investment. Their incomes generally fail to remain ahead of inflation, and therefore, have remained within a narrow band of $40,000 in 1970 dollars. Finally, the demand for physician services cannot be attributed solely to either the consumer (patient) or to the supplier (physician). Rather, the demand for medical services appears to be a unique combination of the two. In conclusion, medicine still is an attractive career path, but the choices and consequences are becoming much more demanding. PMID- 2603156 TI - Cost containment forces physicians into ethical and quality of care compromises. AB - Contemporary cost containment measures ignore patients' need for privacy, destroy long-term doctor-patient relationships, and demand ethical and standard of care compromises. Economic considerations have distracted the physician and he/she no longer focuses primarily on the patient's welfare. The superficiality of the doctor-patient relationship and the cost-cutting efforts have jointly contributed to the deterioration of the quality of medical care. The purpose of this paper is to illustrate that the care physicians dispense in the office is adversely affected by cost containment regulations. PMID- 2603157 TI - The health needs of the majority versus the health needs of the individual: the reorganization of medical education in Colombia. AB - The challenge of excellence in community health services has been taken up by medical educators in Colombia. Confronted with a nation where the primary indicators of disease mortality and morbidity (cardiovascular disease and infant mortality) were characteristic of First and Third World patterns, respectively, the Ministry of Health and La Asociacion Colombiana de Facultades de Medicina (ASCOFAME), representatives of institutions of medical education, have collaborated to conduct a needs assessment of the country's health needs and devised an implementation plan designed to better address the needs of the majority of that nation's people. As a model, the Colombian reorganization of medical education is an example which could be emulated by the U.S. where policy makers are struggling with troublesome questions of cost, equity and quality. PMID- 2603158 TI - The physician in the technological age. AB - Translator's summary and notes: Karl Jaspers (1883-1969) argues that modern advances in the natural sciences and in technology have exerted transforming influence on the art of clinical medicine and on its ancient Hippocratic ideal, even though Plato's classical argument about slave physicians and free physicians retains essential relevance for the physician of today. Medicine should be rooted not only in science and technology, but in the humanity of the physician as well. Jaspers thus shows how, within the mind of every medical person, the researcher contests with the physician and the technician with the humanist. Jaspers therefore opposes all modern tendencies that regard men as abstractions. As a creative existentialist influenced by Kierkegaard, Nietzsche, and Husserl, he reasons that clinical medicine should always treat patients as irreducable individuals, and his thinking on psychotherapy argues for a realm of interiority, freedom, intelligibility, and existential communication that transcends the reach of the causal thinking of natural science. This essay, written in 1959, reflects Jaspers' lifelong preoccupation with the philosophical meaning of medicine (he received his MD degree in 1909) and the totality of the human person. It should significantly enhance our own comprehension of medical power, dangers, reasoning, and accomplishments. PMID- 2603159 TI - Effects of p-xylene inhalation on axonal transport in the rat retinal ganglion cells. AB - Although the solvent xylene is suspected of producing nervous system dysfunction in animals and humans, little is known regarding the neurochemical consequences of xylene inhalation. The intent of this study was to determine the effect of intermittent, acute, and subchronic p-xylene exposure on the axonal transport of proteins and glycoproteins within the rat retinofugal tract. A number of different exposure regimens were tested ranging from 50 ppm for a single 6-hr exposure to 1600 ppm 6 hr/day, 5 days/week, for a total of 8 exposure days. Immediately following removal from the inhalation chambers rats were injected intraocularly with [35S]methionine and [3H]fucose (to label retinal proteins and glycoproteins, respectively) and the axonal transport of labeled macromolecules to axons (optic nerve and optic tract) and nerve endings (lateral geniculate body and superior colliculus) was examined 20 hr after precursor injection. Only relatively severe exposure regimens (i.e., 800 or 1600 ppm 6 hr/day, 5 days/week, for 1.5 weeks) produced significant reductions in axonal transport; there was a moderate reduction in the axonal transport of 35S-labeled proteins in the 800-ppm treated group which was more widespread in the 1600 ppm-treated group. Transport of 3H-labeled glycoproteins was less affected. Assessment of retinal metabolism immediately after isotope injection indicated that the rate of precursor uptake was not reduced in either treatment group. Furthermore, rapid transport was still substantially reduced in animals exposed to 1600 ppm p-xylene and allowed a 13 day withdrawal period. These data indicate that p-xylene inhalation decreases rapid axonal transport supplied to the projections of the rat retinal ganglion cells immediately after cessation of inhalation exposure and that this decreased transport is still apparent 13 days after the last exposure. This decreased supply of cellular materials to the axon and nerve ending regions could initiate the neuronal malfunction reported in solvent-exposed animals and humans. PMID- 2603160 TI - Abnormal neurulation induced by 7-hydroxy-2-acetylaminofluorene and acetaminophen: evidence for catechol metabolites as proximate dysmorphogens. AB - Direct additions to culture media of either acetaminophen (APAP) or 7-hydroxy-2 acetylaminofluorene (7-OH-AAF) resulted in abnormal closure of the anterior neuropores of cultured rat embryos in the absence of an exogenous bioactivation system. Concentrations required to produce a 50% incidence of the defect were approximately 500 and 250 microM for APAP and 7-OH-AAF, respectively. Losses of viability were not evident at these concentrations but 7-OH-AAF elicited a somewhat greater effect on growth parameters and generalized embryotoxicity. Transplacental induction with 3-methylcholanthrene (MC) of P450IA1 in subsequently cultured rat embryos did not detectably alter the capacity of APAP or 7-OH-AAF to effect embryotoxicity or neuropore closure. However, additions to the culture medium of exogenous hepatic bioactivating systems (S9) from MC induced vs phenobarbital (PB)-induced adult rats produced profoundly different effects on neuropore closure. Coincubation with S9 from MC-induced rats reduced the incidence of 7-OH-AAF-elicited abnormal neuropores from 45 to 19%, whereas coincubation with S9 from PB-induced rats increased the incidence to 77%. Coincubation with MC-induced S9 produced no statistically significant effect on APAP-elicited neuropore abnormalities but, with PB-induced S9, resulted in a significant increase from 60 to 86%. Additions of 3-OH-APAP (0.1-0.2 mM) but not N-acetyl-p-benzoquinoneimine (NAPQI, 0.1-0.5 mM) to the culture medium elicited the typical neuropore abnormality. Experiments with APAP and 7-OH-AAF as substrates demonstrated that embryonic enzymes catalyzed their conversion to the corresponding catechols. Considered together, the results provided evidence that embryonic conversion of APAP or 7-OH-AAF to the corresponding catechol metabolites may be instrumental in effecting the abnormal anterior neuropore closure observed after exposure of embryos to the respective parent compounds. PMID- 2603161 TI - Cadmium inhibition of L-alanine transport into renal brush border membrane vesicles isolated from the winter flounder (Pseudopleuronectes americanus). AB - Using isolated brush border membrane vesicles from the kidney of the winter flounder (Pseudopleuronectes americanus), we have studied the effect of cadmium on L-alanine transport. Pretreatment of vesicles with 0.1 mM Cd2+ resulted in inhibition of L-alanine uptake in the presence of a NaCl (but not KCl) gradient. Inhibition was due to a specific interaction with the sodium-alanine cotransport system and not a change in the driving forces for alanine transport, since Cd2+ did not affect sodium-dependent D-glucose uptake. The effect of Cd2+ on Na+ alanine cotransport showed mixed-type inhibition which is only partially reversible by EDTA. Cd2+ uptake itself was shown to be time and temperature dependent, resulting in binding to both sides of the membrane. No direct correlation was possible between inhibition of L-alanine transport and the amount of Cd2+ taken up by the membranes. Nevertheless, the striking time dependence of the effect of Cd2+ on sodium-dependent L-alanine uptake and the inability of EDTA to reverse the inhibitory action of Cd2+ suggest that Cd2+ inhibits Na+-alanine cotransport at the cytoplasmic side of the membrane. PMID- 2603162 TI - Toxic and nontoxic changes induced in the urothelium by xenobiotics. AB - Urothelial carcinogenesis progresses through several morphologically identifiable stages from simple hyperplasia, to nodular and papillary hyperplasia, to papilloma, and to noninvasive and invasive carcinoma. Unfortunately, no specific identifiable markers on any of the early lesions are available to distinguish those which will become neoplasms from those that are potentially reversible. Urothelial toxicity secondary to cyclophosphamide injection also progresses through several phases, beginning with vacuolization of the epithelium, to necrosis and ulceration, followed by an inflammatory infiltrate, granulation tissue formation, and marked regenerative hyperplasia of the epithelium, with ultimate repair and return to normal. Numerous changes related to toxicity are similar to those seen during carcinogenesis. In addition, several apparent morphologic "changes" occurring in the adult bladder can be mistaken for evidence of toxicity, and more importantly, many of the changes seen during regenerative repair and during carcinogenesis occur in the normal fetal urothelial development. PMID- 2603163 TI - Proliferative changes in the prostate. AB - The prostate of the rat has several lobes which have variable responsiveness to estrogens and testosterone. Testosterone is a major stimulant of cell proliferation in the prostate. Chemical carcinogenesis models in the rat prostate have taken advantage of administering the carcinogen during the peak proliferative period following testosterone administration with subsequent testosterone administered to continue the proliferative stimulus. Invasive adenocarcinomas of the prostate have been induced utilizing such methods. PMID- 2603165 TI - Contemporary initiatives in quantitative toxicology. Proceedings of the 18th Conference on Toxicology. November 1-3, 1988, Dayton, Ohio. PMID- 2603164 TI - Correlation between behavioral and pathological changes in the evaluation of neurotoxicity. AB - Recently the EPA has implemented new guidelines under Section 4 of TSCA to undertake neurotoxicity testing. It is expected that other agencies, both national and international, will follow suit. The evaluation of neurotoxicity will be based primarily on behavioral and morphological observations and particularly on the correlation between them. Initially, considerable information will have to be gathered from various laboratories to form the background data on which decisions of toxic effects can be made. This paper presents our experience to date with behavioral and neuropathological procedures for the evaluation of chemical compounds or dietary regimens in rats for potential neurotoxicity. Reference is made to acrylamide, 2,5-hexanedione, 3,3'-iminodipropionitrile, amphetamine, physostigmine, ethanol, triethyltin, food and water deprivation, and carbon tetrachloride. The question of whether every change induced by xenobiotics can be considered as a sign of toxicity is discussed. PMID- 2603166 TI - A QSAR model for the estimation of carcinogenicity: example application to an azo dye. AB - Since carcinogenicity bioassays are time-consuming, costly, and use animal resources, structure-activity relationship equations which model toxicological end-points have been developed to make available alternative methods which approximate the results that could be obtained from bioassays but which are less expensive and time-consuming and use fewer, if any, animals. These equations are based on sets of bioassay results and explain the end-point under consideration in terms of substructural and other parameters which describe the chemical entities. The resulting equations--or models--can then be used to estimate--or predict--the end-point for new structures. The estimation is followed by validation procedures. PMID- 2603167 TI - A computer-assisted procedure for the assembly and analysis of short-term genotoxicity test data. AB - Determining the genetic hazard of a chemical is generally approached by using an assortment of tests for measuring the DNA reactivity of a chemical or its resultant genotoxicity. Over 100 short-term tests employing a wide diversity of species and genetic mechanisms have been used to measure genetic hazard. To date, attempts to achieve a standard test battery for defining genetic hazard have not been successful. Consequently, testing for genetic hazard involves the use of test batteries with variable types and numbers of assays. This increases the difficulties of interpreting data sets since the data sets are often filled with inconsistent responses from diverse types of assays. Several years ago, the International Commission for Protection Against Environmental Mutagens and Carcinogens (ICPEMC) established a Committee to develop a method to compile and interpret diverse short-term test data. The Committee has produced a quantitative weight-of-evidence approach that combines test data using certain parameters such as dose, replication, and metabolic capacity into a series of scores for test type, test class, test family, and an overall score that defines the total weight of-evidence regarding the genetic hazard of the agent. A description of the method and results from the evaluation of selected chemicals is provided. PMID- 2603169 TI - 1989 state of the Association. PMID- 2603168 TI - Atmospheric chemistry of propellant vapors. AB - Hydrazine fuels are used as examples of the relatively rapid chemical processes which may occur when propellants are released into the atmosphere from normal handling or during accidents. The experimental procedures used to study these processes are reviewed along with postulated chemical reaction mechanisms and measured reaction rates and products. Results show that chemical processes which occur on a time scale comparable with meteorological processes must be considered in the development of dispersion models. These models must also account for the potential formation of toxic reaction products. PMID- 2603170 TI - Metabolism of estrogens by rabbit blastocysts: formation of estrogen glucosides and preferential conversion of estrone to estradiol-17 beta. AB - When day 6 rabbit blastocysts were cultured (3 embryos/mL) in medium 199 containing 3.68 microM estradiol-17 beta (E2), 40% of E2 was metabolized in 24 h, at a rate of 18 pmol/embryo(b)/h, yielding 4 major metabolite fractions. Two of them were identified to be estrogen glucosides: 17 beta-hydroxyestra-1,3,5(10) trien-3-yl beta-D-glucopyranoside (E(2)3G) (12 pmol/b/h) and 17-oxoestra 1,3,5(10)-trien-3-yl beta-D-glucopyranoside (E(1)3G) (0.5 pmol/b/h). If the blastocysts were cultured in 3.68 microM E1 medium, 75% of E1 was metabolized in 24 h (34.1 pmol/b/h); most of it appears as E2 (8 pmol/b/h), E(1)3G (16 pmol/b/h), and E(2)3G (6 pmol/b/h). Thus, the 17 beta-hydroxysteroid dehydrogenase activity in the rabbit blastocysts catalyzes mainly in the direction of the E1----E2 conversion, with little or no E2----E1. This may be responsible in part for the faster metabolism of E1 than E2 by the rabbit blastocyst. In comparison with the rat, mouse, and hamster blastocyst, the rabbit embryo shows an additional capability to conjugate large amounts of estrogens into glucosides by steroid glucosyltransferase. PMID- 2603171 TI - Synthesis and pharmacological evaluation of conjugates of prednisolone and non steroidal anti-inflammatory agents. AB - Esters of prednisolone with ibuprofen and indomethacin were prepared by coupling the 21-hydroxy moiety of the glucocorticoid to the carboxylic group of the non steroidal anti-inflammatory agents. The local and systemic anti-inflammatory activities of the conjugates were evaluated using the cotton pellet granuloma bioassay and their topical activity evaluated by the croton oil-induced ear edema assay, in male Sprague-Dawley rats. The results indicate that these conjugates possess greater local and topical anti-inflammatory activity than prednisolone. In the subacute ear edema bioassay, the conjugates displayed no discernible untoward systemic effects, unlike prednisolone and prednisolone acetate, which elicited significant adverse systemic effects, at equipotent doses. These findings suggest that the chemical coupling of prednisolone and non-steroidal anti-inflammatory agents produced compounds with enhanced anti-inflammatory potencies and reduced systemic toxicities, particularly when administered topically. PMID- 2603173 TI - [Does pure old age exist?]. PMID- 2603172 TI - Synthesis and photochemical reactions of nitroestrogens: possible photoaffinity labels of zero length. AB - The syntheses of 3,4-dimethoxy-1,3,5(10)-estratrien-17-one and 4-bromo-3-methoxy 2-nitro-1,3,5(10)-estratrein-17-one are described and their photoreactions with amines and hydroxide ion studied. The possible usefulness of these new steroids as photoaffinity labels of zero length is discussed. PMID- 2603174 TI - [Mutual concept formation of older and younger subjects. Stereotyping and distribution preferences]. AB - This article analyzes the extent to which younger and older persons are apt to stereotype and discriminate age groups. Several hypotheses are tested based on a recent (1987) large scale national Dutch survey. No evidence is found for the hypothesis that positive attributes are systematically more ascribed to younger people and negative attributes systematically more to older people. Only a small minority of the Dutch population holds negative images of older people. A large majority does not discriminate between age groups or finds positive attributes more characteristic of older people. It is demonstrated, however, that older people have a more positive perception of older people - or a more negative perception of younger people - than younger people. In accordance with our hypothesis, negative stereotyping of older versus younger people is related to authoritarian attitudes and a general tendency to social discrimination. The assumption that both older and younger people favour their own age group in (hypothetical) distributions of scarce goods and tasks is in general not supported. On the contrary both age groups, especially the elderly, exhibit a surprising willingness to support the other age group. PMID- 2603176 TI - [Reversible dementias: assessment of treatment effects]. PMID- 2603175 TI - [Visual pattern analysis and reasoning: Ravens' Coloured Progressive Matrices in old-age and very-old-age adults]. AB - Sixty-five non-demented elderly adults, born between 1895 and 1918 (mean age +/- sd: 80.0 +/- 5.4) were tested with Raven's Coloured Progressive Matrices (CPM). Subjects were recruited from homes for the aged and were rated by the staff as free from any symptoms of dementia or other psychiatric disease. Mean number of years of education was 8.2 (range 5 to 18). CPM scores ranged from 9 to 35 with mean +/- sd of 25.9 +/- 5.9. Subjects who had received more formal education performed better on the CPM (Pearson's r: 0.49). When education was controlled for in the analysis, the correlation between age and performance was attenuated and did not reach statistical significance (Pearson's r: -0.24). Test results appeared to be specific for generations, regardless of age. Mean performance in this sample was significantly higher than less recently published norms suggest. Analysis of item content revealed that the CPM consists of three main types of problems: two of a predominantly visuospatial type (12 items of simple continuous pattern-completion and 15 concrete items showing progressive changes in one or two directions) and 9 items of an abstract reasoning type. The concrete visuospatial items appear very useful in the assessment of visuoperceptive dysfunction, as for example in visual apperceptive agnosia. The abstract matrices were very difficult for most of our elderly subjects, so that these items cannot be used to detect deviations from normal old age. PMID- 2603177 TI - Understanding informed consent. AB - The failure of a physician to disclose all of the risks associated with an operative procedure is considered a breach of professional duty and, therefore, a negligent act. Consent for a procedure does not necessarily have to be written; however, signed forms provide written evidence of the patient's agreement. Documentation is essential, especially in cases where the consent form is incomplete or incorrectly filled out. Any concerns about a patient's consent or lack of consent should be discussed with the surgeon. PMID- 2603178 TI - Facing the fear of speaking in public. AB - The tools and talents of public speaking can help in many ways that do not involve a lectern. The steps involved in preparing a speech can help organize any problem-solving discussion. Effective speaking ability is an asset in most professions, and your success or failure in this area affects the others' perceptions of your professional capacity. PMID- 2603179 TI - Gamma knife performs brain surgery without incision. PMID- 2603180 TI - Challenging choices for nurses. PMID- 2603181 TI - Anger--how to deal with it on the job. AB - Anger is not always, and does not always have to be, negative; however, anger in the workplace is often an obstacle to efficiency and negatively affects the work environment. Anger can force the manager to deal with irritants that have been avoided and can result in constructive change. Aside from impairing logical thinking, anger negatively affects problem solving by creating emotional barriers between individuals. Appropriate intervention into anger can enhance not only the manager's personal feelings of well-being but also the health of the organization. PMID- 2603182 TI - Low prevalence of HIV infection in Djibouti--has the AIDS epidemic come to a stop at the Horn of Africa? AB - To determine if the HIV-epidemic had reached Djibouti by autumn 1987, we investigated 645 subjects belonging to various risk groups; 150 were patients with a disease compatible with acquired immune deficiency or with a mycobacterial infection, 115 were young males having a sexually transmitted disease, 295 were female prostitutes, and 69 were villagers from a rural area; the remaining 16 belonged to other groups. All subjects answered an epidemiological questionnaire and had their serum tested for evidence of HIV antibodies. Eight sera were HIV antibody positive by both ELISA and Western blot. Of these, 2 were from young men while 6 were from young women who admitted to prostitution. This accounts for an HIV seropositivity rate of 2.0% +/- 1.6% in the prostitute population. Also, one antibody-positive subject was positive for circulating HIV antigen. Seven of the seropositive individuals had no general complaints or abnormal clinical signs. The eighth subject was a 28 year old man in hospital for pneumonia. We conclude that in Djibouti, in late 1987, the prevalence of both AIDS and HIV infection in high risk individuals was much lower than that reported from other East African countries. PMID- 2603183 TI - Incidence of intramuscular injections in rural dispensaries in developing countries. PMID- 2603184 TI - Ethnic differences in the prevalence of hepatitis delta agent in Djibouti. PMID- 2603185 TI - HIV infection presenting as Guillain-Barre syndrome in Lusaka, Zambia. PMID- 2603186 TI - Subacute sclerosing panencephalitis in South Africa. PMID- 2603187 TI - Rapid laboratory diagnosis of cholera in the field. PMID- 2603188 TI - Antibiotic-multiresistant Salmonella typhi in Egypt. PMID- 2603189 TI - The epidemiology of leprosy in a high prevalence village in Papua New Guinea. AB - In a village of about 1000 people in Papua New Guinea the prevalence of clinical leprosy was 8.6% compared to about 3% in surrounding villages. This exceptionally high prevalence could not be explained by recent introduction of the disease or by social factors. Dapsone-resistant disease and faulty compliance with treatment are considered to be contributory to persistent infectivity of old cases which, together with the presence of 20 previously undiagnosed cases, comprised a large infective source. Social ostracism of cases was not observed and the extensive social mixing of all ages would facilitate widespread dissemination of infection. A high prevalence, particularly in children, of elevated levels of IgM antibody to phenolic glycolipid-1 Mycobacterium leprae specific antigen suggests frequent subclinical infection. The greater prevalence of clinical leprosy following childhood in the village favours altered susceptibility following exposure in childhood. There was a higher prevalence of leprosy in close relatives of cases when compared with the same relatives of age and sex matched leprosy-free controls. The occurrence of familial clustering of leprosy in a hyperendemic area with intense transmission suggests that unidentified inherited factors influence susceptibility to clinical leprosy. It is suggested that the clustering of adverse inherited traits through intermarriage may explain this hyperendemic focus on leprosy. PMID- 2603190 TI - Prevention of diarrhoea and dysentery by hand washing. AB - A 'non-blind' randomized hand washing intervention study was conducted in a low socioeconomic community in Rangoon to determine if hand washing by 494 children under 5 years old and their mothers could reduce the incidence of diarrhoea and dysentery in these children. Children and mothers in the intervention group were asked to wash their hands after defaecation and before preparing or eating their 3 main meals; 2 bars of plain soap were provided. The control group was left to follow customary practice. Diarrhoea and dysentery incidences in the 2 groups were monitored during 4 months by comparing the incidence density ratios (IDR). The diarrhoeal incidence among the children in the hand washing households was significantly lower than that among those in the control households (IDR = 0.70, 95% confidence interval (CI) = 0.54-0.92). For dysentery incidence, although there was a 40% reduction (IDR = 0.58, 95% CI = 0.22-1.55) in the children under 2 years, there seemed to be no impact in older children (IDR = 1.2, 95% CI = 0.52 2.80). The study indicates that hand washing is effective in reducing the morbidity from diarrhoea and dysentery. PMID- 2603191 TI - The epidemiology of leptospirosis in Portugal. PMID- 2603192 TI - Bacterial pathogens isolated from cockroaches trapped from paediatric wards in peninsular Malaysia. AB - A survey was conducted in 4 paediatric wards in Malaysia to determine the distribution of various species of cockroaches and to examine their gut contents for bacteria. Cockroaches were trapped from food dispensing areas (kitchens), store rooms, cupboards and open wards. 104 cockroaches were caught, consisting of Periplaneta americana (67.3%), Blattella germanica (26%), P. brunnea (4.8%), and Supella longipalpa (1.9%). Bacteria were isolated from all cockroaches except 3 P. americana. Many bacterial species were identified, including the pathogenic and potentially pathogenic species Shigella boydii, S. dysenteriae, Salmonella typhimurium, Klebseilla oxytoca, K. ozaena and Serratia marcescens. PMID- 2603193 TI - Campylobacter pylori in dyspeptic subjects: a report from north India. PMID- 2603194 TI - Isolation of Vibrio cholerae non-O1 from cerebrospinal fluid. PMID- 2603195 TI - Paraspinal abscess. PMID- 2603196 TI - Jejunal surface pH measurements in tropical sprue. AB - The mucosal surface pH of jejunal biopsy samples incubated in vitro in Krebs phosphate buffer was measured. Biopsies from 7 healthy individuals or tropical sprue subjects in complete remission had a mean surface pH of 5.8 +/- 0.09, similar to values for normal Caucasian subjects living in the UK. The mean surface pH of biopsies from 20 sprue patients, 6.0 +/- 0.08, was significantly higher (P less than 0.05) than that of the control subjects. Sprue patients could be sub-divided into those with 2 or more abnormal results in 3 intestinal function tests, and those with one or no abnormal test. The 9 low scorers showed a mean surface pH of 5.75 +/- 0.06 resembling the control mean, whereas the 11 high scorers had a higher (P less than 0.01) mean surface pH of 6.17 +/- 0.08. Mucosal surface pH correlated directly with 3 d mean faecal fat excretion and inversely with xylose and vitamin B12 absorption values but not with the nutritional indicators serum albumen, folate or blood haemoglobin levels. As in coeliac disease, mucosal surface pH in the jejunum is elevated above normal in tropical sprue and may reflect the extent to which normal ion transport processes are affected. PMID- 2603198 TI - Sexing simuliid larvae during cytological examinations. PMID- 2603197 TI - Polio outbreak in Algeria. PMID- 2603199 TI - The low prevalence of HBV markers in Nepal. PMID- 2603200 TI - Strengthening health care systems to improve infant health in rural Nepal. PMID- 2603201 TI - Assessment of appropriate child care at district level: how useful are mortality rates? PMID- 2603203 TI - Recession, structural adjustment and infant health: the need for a human face. PMID- 2603202 TI - Government policy and infant health: options for Ghana. PMID- 2603204 TI - Assisting national governments to improve infant health: the case of Zimbabwe. PMID- 2603205 TI - Reduced infant mortality: a societal indicator, an emotional imperative, or a health objective? PMID- 2603206 TI - Community health workers in national programmes: the case of the family welfare educators of Botswana. AB - Community health worker programmes have become a prominent feature of many primary health care schemes in developing countries. This paper, which is based on a larger collaborative study undertaken in 3 countries, focuses on the experiences with such workers in Botswana, and concludes that many of the key issues that were highlighted in the Botswana study are similar to those in other countries. These can be summarized under four headings: unrealistic expectations, poor initial planning, problems of sustainability, and the difficulty of maintaining quality of care. The future success of these workers will depend on their being integrated more systematically into local services, with concomitant strengthening of management support and supervision. PMID- 2603207 TI - Determinants of infant mortality trends in developing countries--some evidence from Sao Paulo city. PMID- 2603208 TI - Comparison of antimalarial efficacy of artemisinin (qinghaosu) and arteether against Plasmodium cynomolgi B infection in monkeys. AB - Arteether (30:70 mixture of alpha and beta epimers) used as injectable intramuscular preparation (in neutralized ground-nut oil) had curative action at 5 mg/kg x 3 d against blood-induced Plasmodium cynomolgi B infection in rhesus monkeys, while the curative dose of artemisinin (qinghaosu) oil suspension was 10 mg/kg x 7 d or 20 mg/kg x 3 d. Parasite clearance with arteether was achieved within 24 h. Neither arteether nor artemisinin exhibited any causal prophylactic or radical curative action up to dose levels of 20 mg/kg against sporozoite induced P. cynomolgi B infection in rhesus monkeys. PMID- 2603209 TI - Malarial antibody in Nigerian children born abroad after their return home. AB - Prophylaxis of malaria and frequency of clinical attacks were studied in a group of Nigerian children who were born abroad and recently returned home. Two control groups of young children, born and resident in Nigeria, were studied in the same way: one group was protected against malaria and the other was not. Malarial immunofluorescent antibody (IFA) was measured in all 3 groups. All the groups had high IFA positivity rates of 79% or over, but titres were low in the children born abroad, higher in the Nigerian-born protected children, and highest in the unprotected group. Frequency of clinical malaria was the same in both groups of protected children whether born abroad or locally. There appeared to be no long term advantage in giving regular malaria chemoprophylaxis to children of semi immune mothers returning permanently to malarious countries, if the parents were alert to provide prompt treatment of clinical malaria. PMID- 2603210 TI - Clinical study of the treatment of cerebral malaria with artemether (qinghaosu derivative). PMID- 2603211 TI - Successful in vitro isolation and cultivation of Italian dermotropic strains of Leishmania infantum sensu lato. PMID- 2603212 TI - Tropical pyomyositis associated with Trypanosoma brucei rhodesiense infection in a Europid. AB - A 29-year-old European woman became infected with Trypanosoma brucei rhodesiense in the Luangwa valley, Zambia. Six days after the initial presentation of this infection she developed evidence of tropical pyomyositis (TP). These diseases, both of which are rare in Europids, were satisfactorily treated. The pathogenesis of TP, which is nearly always caused by Staphylococcus aureus, is undetermined. It seems possible that in this case either (i) both infections were introduced simultaneously by a tsetse-fly bite, or (ii) T. b. rhodesiense produced multiple focal necroses in skeletal muscles which acted as niduses for the staphylococcal infections; immunodepression caused by this parasite might also have been important. PMID- 2603213 TI - Gastric perforation of amoebic liver abscess: report of a case. PMID- 2603214 TI - Schistosomiasis in Sao Tome. A pilot study. PMID- 2603215 TI - Racemose cysticercosis treated with praziquantel. PMID- 2603216 TI - Chemotherapy of Echinococcus infection in man with albendazole. AB - Since 1983 data have been collected on the outcome of treatment of apparently active Echinococcus granulosus hydatid cysts with albendazole. Most patients received 800 mg albendazole daily in cycles of 28 d with 14 d between cycles, with a mean duration of 2.5 cycles (range 1-12). From an initial set of over 500 cases, 253 patients were evaluated for efficacy, with 269 hepatic, 86 pulmonary, 50 peritoneal and 51 cysts at other sites being individually assessed. 72 patients (28.5%) were regarded as cured, 129 (51%) as improved, 46 (18.1%) as unchanged and 6 (2.4%) were worse. 47 patients underwent surgery after treatment and viability was demonstrated in only 5 cysts (10.6%). Recurrence was observed in 4 of 29 non-surgical cases (13.8%) from whom a follow-up of at least 24 months was available. 35 cases of E. multilocularis infection were assessed, with cure in 2, improvements in 4, stabilization in 25 and progression in 4 cases. Side effects of treatment were uncommon. Liver function abnormalities occurred in about 20% (4% withdrawn) and there was a tendency for leucopenia to occur in E. multilocularis patients. Albendazole appears to be effective both for chemotherapy in inoperable cases of hydatid disease and for prophylaxis before surgery. PMID- 2603217 TI - Descriptive epidemiology of Hodgkin's disease in Italy. AB - Death certification data on Hodgkin's disease in Italy over the period 1955-84 were studied in terms of age-standardized and age-specific national trends, and of geographical variation in mortality. There were substantial declines in death rates from the early 1970's onward, which can be largely attributed to therapeutic improvements. These led to avoidance of about 350 deaths, with a total 950 reported, which is probably the major absolute therapeutic advance identified for any cancer site. The declines started earlier in childhood and young adult age, and were restricted to population below age 60. The age distribution of the disease was different in the two sexes, since the age curve for males showed steady rises up to age 75, whereas that for females was clearly bimodal, with a peak around age 30, and another at oldest age. This divergent pattern is consistent with different exposure to (infectious) agent(s) in children of the two sexes, but also to occupational exposures potentially related to the risk of the disease. Examination of rates in various geographical areas showed generally higher rates in the North, and a few provinces with exceedingly high mortality in the central part of Northern Italy, particularly in a chiefly rural province (Mantua). This excess mortality (and, more in general, the observation that rates for Northern Italy are higher than in any other area of the EEC) could not be explained by obvious diagnostic or classification problems, were evident in both sexes, appeared to be consistent over the last decade and are reflected in available Italian cancer registration data. PMID- 2603218 TI - Risk of breast cancer, diet and internal migrations in northern Italy. AB - The protective effect of birth in southern Italy as opposed to other regions was evaluated in a population-based case-control study of diet and breast cancer among residents in the province of Vercelli. Cases were 250 women with breast cancer diagnosed during 1983-1984 and controls 499 women randomly selected from the general population. The crude relative risk of breast cancer for women born in the south was 0.76 (95% confidence interval, 0.43-1.3). After adjustment for dietary and other potential confounders in multivariate analyses, the protective effect of place of birth disappeared (RR 1.0; 95% CI, 0.57-1.9). The study indicates that north-south differences in the incidence of breast cancer in Italy may in large part be attributed to different dietary habits. PMID- 2603219 TI - Pattern of cervical screening utilization in Italy. AB - The pattern of cervical screening utilization in Italy was analyzed using data from the 1986-1987 National Health Survey on the basis of a sample of 27,455 women aged 20 to 79 randomly selected within strata of municipality of residence and age in order to be representative of the whole Italian population. Overall, about 17% of women aged 20 to 79 were screened per year, for a total of 3.5 to 4 million cervical smears per year. The highest frequency was reported in younger middle age, about one in four women being screened per year in the age groups 30 to 49, and there was a substantial decline above age 50. Cervical smear rates were higher in Northern areas (22%), where mortality from cervical cancer is lower, than in the Centre (16%) and South (11%) of the country. Further, there was a strong positive social class gradient in the utilization of cervical screening, in relation to both education and occupation. In spite of the absence of any organised mass screening program, cervical screening is a relatively common procedure among Italian women. However, this study provides further quantitative evidence of a markedly irrational utilization of non-organized cervical screening, which tends to end up selectively used by the groups in which cervical cancer is less common. PMID- 2603220 TI - Relative role of host and tumor in the growth pattern of murine and human neoplasms following subcutaneous transplantation in mice. AB - The growth patterns of two murine and eight human tumors, bilaterally implanted into subcutaneous tissue of groups of recipient mice, were studied. A Gompertz equation was fitted to experimental data for each individual implant and the Gompertz parameters were utilized as quantitative growth characteristics. The relative roles of the tumor-implanted flank (right versus left), of the individual host and of the tumor were analyzed by the paired t-test, simple linear regression model, one-way and two-way analysis of variance. Sixty pairs of Gompertz curves were obtained in seventy animals. Heterogeneity was the main characteristic of the growth pattern in all tumors under study, with a wide variability among the Gompertz parameters. Statistical analysis of experimental data showed that only the tumor systematically influenced the growth characteristics, whereas neither the tumor-implanted flank nor the individual host played a significant role. These results have both theoretical and practical implications. PMID- 2603221 TI - Neoadjuvant chemotherapy for localized Ewing's sarcoma of the extremities: preliminary results of a protocol which uses surgery (alone or followed by radiotherapy) for local control. AB - From June 1983 to December 1985, thirty-eight patients with localized Ewing's sarcoma of the extremities were treated with a protocol that consisted of an initial nine week period of polychemotherapy (vincristine, adriamycin and cyclophosphamide) followed by local therapy and additional chemotherapy (vincristine, adriamycin, cyclophosphamide and dactinomycin) for one year. As local treatment all patients were offered surgery; thirty-two accepted and six refused. These six patients were locally treated with radiotherapy alone (50 Gy). In the remaining patients an amputation was performed in one case and a resection in thirty-one. In resected patients when a wide margin was achieved (24 cases) no further local treatment was performed; when it was marginal (5 cases) or intralesional (2 cases) radiotherapy at lower doses (40 Gy) followed. At mean follow-up of thirty-seven months the percentage of continuously disease-free patients was 50% for those treated with radiotherapy, 76% with surgery, and 85% with surgery and radiotherapy. Eight patients developed metastatic disease and two patients had local recurrence and metastases. The local recurrences were seen in one patient locally treated with surgery and in one locally treated with radiotherapy. Nine major local complications were observed: three in patients treated with radiotherapy, five in patients treated with surgery, and one in a patient treated with surgery and radiotherapy. These results indicate that after induction chemotherapy conservative surgery is possible in almost all cases of Ewing's sarcoma of the extremities and that such treatment is better than radiotherapy alone as local therapy. PMID- 2603222 TI - Fine-needle aspiration cytodiagnosis of the "cold" thyroid nodule. AB - The results of 1886 fine-needle cytoaspirations of solid, palpable thyroid nodules, "cold" on scintiscanning, performed between 1 January 1978 and 31 December 1986, were analyzed. In total 36 diagnoses of malignancy were made (1.9%). The results of cytologic and histologic examinations were compared in 114 cases to verify the diagnostic accuracy of this method; there was agreement in 98 cases and discordance in 16 consisting of 13 false negatives (11.4%) and 3 false positives (2.6%). The sensitivity was 77.9%, specificity 94.5%, positive predictive value 93.8%, negative predictive value 80% and test efficiency 86%. These values are in the range of those reported in the literature and confirm the validity of fine-needle aspiration cytology in the preoperative diagnosis of thyroid neoplasms. PMID- 2603224 TI - Pancreatic metastasis 25 years after nephrectomy for renal cancer. AB - The authors report a case of renal cell carcinoma metastasis to the pancreas occurring 25 years after nephrectomy. The need for prolonged follow-up of patients is emphasized. The surgical approach is considered the best way to deal with such late metastases. PMID- 2603223 TI - Tumor markers in serum of patients with primary squamous cell carcinoma of the esophagus. AB - Serum levels of several tumor markers were studied in 96 patients with untreated primary squamous cell carcinoma of the esophagus. Three markers specific for digestive tract malignancies--CEA, CA19.9 and CA50--and two non organ specific indicators of malignancy--ferritin and TPA--were evaluated. Positivity rates of CA19.9 and CA50 were very low (4.4% and 8.6% respectively); the markers were therefore considered ineffective in the disease. CEA, TPA and ferritin showed a fair positivity rate (27.1%, 28.1%, 33.7% respectively); CEA and TPA were directly related to clinical stage, CEA levels being significantly higher in stage IV than in stage III cases (p = 0.016). TPA preoperatory levels were also directly related to a lower survival probability (p = 0.004). CEA showed significantly lower levels in tumors of lower than in those of middle (p = 0.03) and upper esophagus (p = 0.004). TPA showed a similar behaviour with lower levels in tumors of lower than of middle esophagus (p = 0.03). These findings could be due to a bulky metabolism of tumor markers drained via portail vein in the liver. From our data the following conclusions may be drawn: 1) CEA and TPA may be useful in the staging of esophageal cancer as an ancillary tool to assess the extent of the disease; 2) tumor location is an important variable when evaluating blood levels of tumor markers in patients with esophageal cancer. PMID- 2603225 TI - [Cocaine and crack]. PMID- 2603226 TI - [Are health examinations of pregnant women enough?]. PMID- 2603227 TI - [AIDS/HIV: risk for surgeons--new surgical routines]. AB - The surgical team is at risk of transmission of human immunodefiency virus (HIV) from the patient, which could progress to AIDS and death. In our hospital, we have estimated a probability of 0.20% per year, and 5.82% for 30 years in surgery. In view of this we have designed new procedures for surgical handicraft to reduce the risk from splash or injury to the surgical team. The surgeon must handle tissue with instruments only and minimize the use of fingers. Sharp instruments should, if possible be replaced by blunt types. The nurse loads needles to the needle carrier using a forceps. Sharp instruments are placed in a neutral zone on the nurse's stand so that the surgeon and nurse never touch the same sharp instrument at the same time. Movements must be controlled and accompanied by eye contact. The measures to prevent injury would hardly affect the individual skill of the surgeon or prolong operation time. We consider that the new routines suggested prevent transmission of HIV during surgical procedures better than by knowing the HIV status, of the patients. PMID- 2603228 TI - [Myotonic dystrophy. Genetic, neonatologic and neuropsychological aspects]. AB - Dystrophia myotonica (DM) is an autosomally dominant hereditary multi-organ disease which is characterized primarily by myotonia and muscular atrophy and thereafter by cataract and disturbances in cardiac conduction. The prevalence is stated to be 2.5-5.5 per 100,000. The disease may be manifest at birth or may become manifest later, right up to the age of 60-70 years, on an average about the age of 20 years. The earlier the commencement of the disease, the more severe the course and the condition becomes crippling. The survival is reduced on an average by 25 years. The diagnosis is based on the clinical findings, information about familial occurrence of DM, electromyography and split lamp examination. The penetration of the DM gene is practically 100% by the age of 14 years but the expression varies greatly. By examination of chorion villi in informative families it will be possible to predict with 96-98% probability whether an embryo will develop DM or not. Genetic research in recent years has rendered prenatal diagnosis possible and diagnosis of the DM gene prior to conception in clinically healthy family members. No specific treatment is available. PMID- 2603229 TI - [Preventive health examinations of pregnant women in Denmark. Structure and organization]. AB - In Denmark, pregnant women are offered antenatal care in a nationwide programme. This programme is organized around health examinations in general practice, midwives centres and hospital outpatient departments. During the winter 1986/87 a nationwide investigation of antenatal care was carried out in Denmark. A random sample of approximately 1/3 of the general practitioners, all of the midwives who had antenatal consultations and the medical staffs of 26 departments of obstetrics and gynaecology with more than 100 deliveries in 1985 received a questionnaire about the content of a definite antenatal examination and certain conditions of organization. The obstetricians could describe three different types of antenatal examinations depending upon the place and arrangement of work. The percentage replies received were 62 for general practice, 86 for the midwives and 62, 69 and 55 from the doctors in the place of delivery. 50% of the pregnant women had been attached to the same practice for at least five years. 70% of the general practitioners performed approximately one antenatal examination weekly. Only few hospital districts had attempted to have the first examination by the midwife at the 12th week of pregnancy. 25% of the places for examination by midwives were outside hospitals, which, according to the guidelines for antenatal care, do not entirely fulfill the intentions concerning situation in the patient's immediate surroundings. All of the obstetric departments offered routine examinations in the 16th-18th weeks and a number of these also routine examinations in the third trimester.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2603230 TI - [Preventive health examinations of pregnant women in Denmark. Education, supervision and postgraduate education]. AB - A questionnaire about the content of a concrete antenatal examination and their own qualifications was sent to a random sample consisting of 1/3 of general practitioners in Denmark, all of the midwives who had antenatal consultations, the medical staffs of 26 departments of obstetrics and gynaecology and 26 surgical departments with more than 100 deliveries in 1985. The medical staffs could describe three different types of antenatal examinations depending upon the place and function. The percentages of replies received were 62 for general practice, 86 for midwives and 63, 69 and 55 for the medical staffs of the institutions involved. 49% of the general practitioners had worked in departments of obstetrics and gynaecology for at least six months. 62% of the doctors who described antenatal examination in week 16-18 were house officers or registrars and 28% were specialists. Among the medical staff who described an antenatal examination of a woman with an at risk pregnancy, 61% were consultants or senior registrars and 49% were specialists. The commonest goal for postgraduate training where non-specialists were concerned was general practice. Supervision in one form or another was possible in all of the departments participating, as a rule because an experienced colleague was present in the outpatient department. Supervision may be improved by alterations in the working arrangements. PMID- 2603231 TI - [Cesarean section under epidural anesthesia. A questionnaire study]. AB - Seventy-four women selected at random who had been subjected to Caesarean section replied to questions about their satisfaction with epidural anaesthesia at various stages during the intervention. General discomfort increased during the intervention and pain contributed most to this. 96% of the women would recommend the method to others. PMID- 2603232 TI - [Coxarthrosis and paramedical contact]. AB - In a material consisting of 194 patient with arthrosis of the hip joint, waiting for alloplastic operation, the incidence of alternative treatment and the pattern of this was investigated. 43% had been treated by alternative methods. Eighty eight per cent had sought alternative treatment because of hip pain. No differences in user frequency and pattern were found in Odense and Holstebro. The use of alternative treatment was unrelated to the duration of pain, pain intensity, sex and age. PMID- 2603233 TI - [Button batteries. Treatment of children who have swallowed button batteries]. AB - The use, constitution and identification of commercially available button batteries are described. Most cases of button battery ingestion in children are asymptomatic and without complications. Possible complications are reviewed. Most cases described are due to burns in the esophagus or leakage of contents. The danger of intoxication is presumably only present in the case of mercury cells and, even here, it is minimal. If passage of esophagus (for the bigger types pylorus) can is confirmed by x-ray, treatment is conservative observation. If the button battery is present in the esophagus, acute surgical/endoscopic removal are indicated. Possibilities for prevention is described. PMID- 2603234 TI - [Automated inflation and regulation of the pressure in infusion cuffs]. AB - Construction of a pressure regulator with connected tube and reservoir system for use in rapid intravenous infusion is described. This system is easy to construct, easy to employ and suitable for rapid correction of severe hypovolumaemia. PMID- 2603235 TI - [Causes of death in surgically treated ulcer patients. Results from the Aarhus County Vagotomy Trial]. AB - It is a well-known observation that patients submitted to operation for benign duodenal or gastric ulceration have reduced long-term survival as compared with the basic population. This excessive mortality may attributed to association between peptic ulceration and other conditions, particularly pulmonary disease, cirrhosis of the liver and suicide. In order to investigate whether there is a difference in the pattern of causes of death in patients treated with classical gastric resection and patients treated the vagotomy methods employed in recent years, an analysis of the causes of death in 169 patients was undertaken. During the years 1972-1977 these patients had been treated with selective gastric vagotomy with drainage, selective gastric vagotomy with antrectomy, parietal cell vagotomy with or without drainage for duodenal ulceration, pyloric ulceration, prepyloric ulceration or combined ulceration. This is termed the Aarhus County Vagotomy Trial. Comparison with the basic population reveals statistically significant excessive mortality from gastro-intestinal disease including the subgroups benign ulcer disease and cirrhosis of the liver and accidents including the subgroup of suicide. The mortality from malignant conditions did not differ significantly from the control group with the exception of significantly increased incidence of cancer of the stomach. The death ratio was increased for cancer in the lungs and pancreas but this was not statistically significant. These results are in agreement with reviews based on resection materials apart from the observation that a significant excess mortality from cancer of the stomach was demonstrated in this patient group in the present investigation which is not a constant finding in previous investigations. In addition, no increased incidence of benign pulmonary disease could be demonstrated. PMID- 2603236 TI - [Intraosseous ganglia of the carpal bones]. AB - Symptom-producing cystic lesions in the carpal bones may be caused by intraosseous ganglia. Two different types occur: a completely intraosseous type and a rarer penetrating type. Two cases of the latter type are presented. In both of the types, the symptoms consist of pain following prolonged stress. In the penetrating type, a soft tissue tumour can be palpated. A cystic region of decalcification is visible radiographically. As a rule, no degenerative joint changes are encountered. Treatment consists of emptying of the cyst and bone transplantation in rare cases. Recurrence is rare. PMID- 2603237 TI - [Perforation of the nasal septum caused by a miniature battery]. PMID- 2603238 TI - [The intraosseous ganglion. The differential diagnosis of pain in the forefoot]. AB - The intraosseous ganglion is a rare benign cystic lesion of bone which is frequently located in close association with the articular cartilage of the distal metaphysis of long bones. In many cases, it is clinically silent but it may cause persistent pain. The commonest location is at the ankle. It appears radiographically as a well-demarcated circular or oval radiotranslucent defect surrounded by a thin margin of sclerotic bone. Treatment consists of curettage and bone grafting. PMID- 2603239 TI - [Prevention of HIV-infection and AIDS--information bases for planning and evaluation]. PMID- 2603240 TI - [Treatment of urogenital Chlamydia infections]. PMID- 2603241 TI - Arterial gas embolism as a pathophysiologic mechanism for spinal cord decompression sickness. AB - A continuous infusion of air (1.0 ml.min-1) was delivered via a fine aortic cannula into the arterial circulation of 7 anesthetized dogs until no spinal cord function could be elicited by somatosensory evoked potentials. The animals were then rapidly perfusion-fixed and the spinal cords removed for histological examination. The appearance of the embolized cords differed substantially from eight spinal cords injured by fulminant decompression sickness (DCS). The embolized cords appeared essentially normal whereas the DCS cords featured extravascular, nonstaining, space-occupying lesions (SOLs) scattered throughout the cord, mainly in the white matter. Two spinal cords injured by DCS with a delayed onset (30 min from surfacing) appeared similar to the embolized cords. These findings are compatible with the hypothesis that two mechanisms are involved in the onset of spinal cord DCS. Fulminant disease is associated with SOLs, which are probably caused by the in situ evolution of a gas phase. Disease with a delayed onset is more likely to be caused by an ischemic mechanism, which in the acute phase is histologically indistinguishable from gas embolism. PMID- 2603242 TI - Induction of platelet aggregation in vitro by microbubbles of nitrogen. AB - Microbubbles of nitrogen gas act as a platelet agonist, but the biochemical mechanisms involved in bubble-induced platelet activation are not well known. One characteristic property of a platelet agonist is to potentiate the response by another agonist in a synergistic manner at low concentrations. Possible synergism between N2 gas bubbles and the physiologic agonists ADP, epinephrine, and 5 hydroxytryptamine (5-HT) was tested. The interaction with ADP was additive; N2 microbubbles and ADP had different aggregation profiles, and the bubbles made the reversible ADP aggregation irreversible. Epinephrine caused a strong, synergistic stimulation of bubble-induced platelet aggregation. This synergism was only partially inhibited by indomethacin and acetylsalicylic acid, but abolished by yohimbine. 5-HT had an inhibitory effect on N2 microbubble-induced platelet aggregation. This effect was neutralized by the S2-serotonergic receptor blocker ketanserin. Microbubble stimulation of the platelets before stimulation with ADP, epinephrine, and 5-HT seemed to make them more sensitive to epinephrine only. The strong synergism between microbubbles and epinephrine in vitro should be evaluated for possible future use in predive selection of divers. PMID- 2603243 TI - Treatment of type I decompression sickness using the U.S. Navy treatment algorithm. AB - The effectiveness of the U.S. Navy (USN) Diving Manual treatment algorithm in treating pain-only decompression sickness (DCS) was analyzed. Treatment logs from the Naval Diving and Salvage Training Center and the Navy Experimental Diving Unit during the decade 1976-1986 were examined. Two hundred and ninety-two cases diagnosed initially as pain-only DCS were identified. Using the treatment algorithm, 208 cases were completed on USN Treatment Table 5 (TT-5), and 84 cases completed on USN Treatment Table 6 (TT-6). Recurrence of symptoms was 4.3% after TT-5, and 3.6% following TT-6. Difference in rate of recurrence was not statistically significant between treatment tables. Overall, the success rate for following the USN treatment algorithm was 95.9%. These data support the use of the shorter TT-5 in accordance with the Navy treatment algorithm. PMID- 2603244 TI - Body cooling with ice for warm-water diving operations. AB - Physiologic responses were measured on 2 professional divers exposed to a simulated repair work submersed for 60 min in water at temperatures of 34 degrees, 38 degrees, and 42 degrees C. Exposures were repeated with two types of diving suits; a normal dry, rubber suit (NDS) and this suit worn over an ice cooled vest (ICEDS). Heat balance (lower heat storage) was better maintained at all temperatures with ICEDS. Physiologic strain was significant with NDS in 38 degrees C. At 42 degrees C 1 subject was able to complete 60 min with ICEDS. However, all exposures at 42 degrees C caused an extremely high physiologic strain, more so with NDS. Tolerance times observed were in good agreement with suggested criteria for heat tolerance. An ice-cooled vest, with room for further improvement, allows for at least 15-30 min longer exposure periods in the studied temperature range. PMID- 2603245 TI - [Medicine: the privileged field of the French language speaker. Interview by Robert Henry]. PMID- 2603246 TI - [Diagnosis of genital Chlamydia trachomatis infections using antigen detection and cell culture]. PMID- 2603247 TI - [Scientific evidence: not always evident]. PMID- 2603248 TI - [The mortality associated with asthma in Quebec 1975-1985]. AB - In the last decade, mortality from asthma has increased in most industrialized countries. The analysis of death certificates from 1975 to 1985 for the province of Quebec shows a 28.6% increase in deaths associated with asthma, from 1.43 to 1.84 per 100,000 population. Although the mortality rate from asthma is higher in older patients, a steady increase in mortality rates from asthma have been observed in younger asthmatics (less than 35 years old), with rates going from 0.24 to 0.37 per 100,000. The number of deaths has recently increased more rapidly in women and is not different in rural and urban areas. On the other hand, the number of asthma-related hospitalisations has been stable from 1980 to 1985. This increase in mortality from asthma has been considered multifactorial but stresses the importance of improving asthma control. Proposed solutions to improve this situation, such as patient education on asthma and its treatment, regular measurement of expiratory flows, identification of "at-risk" patients and optimization of the treatment are discussed. PMID- 2603249 TI - [The diagnosis of occupational tuberculosis of hospital personnel using the 2 stage intradermal Mantoux reaction]. AB - Tuberculin skin testing was undertaken among employees of Cite de la Sante in contact with patients when the hospital was first opened in 1978. Since January 1980, two-step testing was done. The rate of the booster phenomenon was 6.9%. In well-documented BCG vaccinated personnel, almost 80% had easily interpretable reactions, either negative or significant. From our data and other data in the literature, we conclude that two-step tuberculin testing should be used if tuberculin skin testing of hospital employees is done in order to detect the booster phenomenon and not to conclude falsely in tuberculin conversion in a subsequent testing. PMID- 2603250 TI - [The pertinence of microscopic analysis of the urine as a diagnostic test for asymptomatic bacteriuria in pregnancy]. AB - The genito-urinary tract is the most frequent site of infection during pregnancy. Asymptomatic bacteriuria is found in 2 to 12% of the obstetrical population. The importance of its detection is underlined by the fact that 20 to 40% of untreated cases will present acute pyelonephritis. Our study's first aim was determining the incidence of asymptomatic bacteriuria in our population. Our results show an incidence of 3.9%. Second, routine mandatory prenatal laboratory examinations include urinalysis and urine culture. Considering the fact that we already do a routine culture, we questioned the pertinence of the microscopic part of urinalysis for screening asymptomatic bacteriuria. Our study has shown that no amount of erythrocytes, leucocytes, bacteria, pus or combination thereof has sufficient sensitivity and/or specificity to be used for screening. We thus conclude that in our context of budget restrictions, the microscopic analysis of urine should be abandoned as a routine test. The biochemical part of urinalysis could be done easily with dipsticks at a lower cost. Urine culture remains the gold standard for detection of asymptomatic bacteriuria. PMID- 2603251 TI - [Current focus on allergy tests]. PMID- 2603252 TI - [Geriatrics: medicine of the future]. PMID- 2603253 TI - [Study of geographic variations: starting point in the reassessment of health services. The phenomenon, its causes and its implications]. AB - This first article, in a series of two, reviews the evidence on geographic variations in the use of health care services. Large variations exist both between countries and between regions within countries. These variations cannot be explained satisfactorily by errors of data, population characteristics or health care system features. Rather, they seem to stem from the professional uncertainty surrounding the current use of health care procedures. In the absence of solid scientific knowledge regarding the relevance and the efficacy of various alternatives, different practice styles are acceptable. Geographic variations raise important questions concerning the cost of care, the health of the population and health policies. In order to deal with geographic variations and professional uncertainty, a major reassessment of health care services is warranted. Specific action strategies will be described in a second article. PMID- 2603254 TI - [Periodic physical examination: 1989 update. Early detection of colorectal cancer]. PMID- 2603255 TI - [The skeleton: a real bazaar! 2]. PMID- 2603257 TI - [Arthrosis: re-evaluations and innovations]. PMID- 2603256 TI - [Fibromyalgia: a mysterious and old fashionable disease]. PMID- 2603258 TI - Medium and long-term complications of endoscopic sphincterotomy for choledocholithiasis. AB - The medium and long-term complications of endoscopic sphincterotomy for choledocholithiasis were examined in patients referred to an endoscopy centre in an area general hospital. One hundred and thirty-eight patients were reviewed between 6 months and 7 years after successful endoscopic sphincterotomy for choledocholithiasis. The procedure was carried out post-cholecystectomy in 69 (50%) and with the gallbladder in situ in 69 patients. Four post-cholecystectomy patients and 10 with intact gallbladders had died by the time of review. A postal questionnaire was completed by the remaining 124 patients. Sixty-two post cholecystectomy and 49 with gallbladders still intact remained symptom-free at follow-up. Eight patients had had the sphincterotomy as a preliminary to cholecystectomy. There were persistent symptoms in three post-cholecystectomy and two with intact gallbladders. Medium to long-term complications are uncommon after endoscopic sphincterotomy for choledocholithiasis. PMID- 2603259 TI - Radiological examination of the small bowel. AB - A retrospective study was made of 100 consecutive dedicated per-oral small bowel examinations. 33% of the studies were abnormal, of which almost half were due to Crohn's disease. When grouped according to clinical suspicion, 73.5% of those studies with a high index of clinical suspicion were abnormal. In the abnormal group a correct diagnosis was made in 90%, with two false positives. In the normal group a correct diagnosis was made in 91%, with no false negatives. It is suggested that the dedicated small bowel series offers a justifiable and practical alternative to other techniques such as intubation and direct infusion of contrast medium into the small bowel, or enteroclysis. PMID- 2603260 TI - Mortality in the elderly during respite hospital care. AB - This study examined the mortality in the elderly during 243 respite hospital admissions. Sixty-four dependent elderly patients entered a regular respite care scheme and were admitted to hospital for a period of 4 weeks out of every 12 weeks. The mortality rate in hospital was one death per 976 days, in comparison to one death per 1296 days at home. This small increase in mortality should not deprive patients and their carers from access to respite care. PMID- 2603261 TI - Mortality rates of patients admitted to a psychogeriatric assessment unit. AB - Admission of elderly people to a geriatric hospital may carry an increased risk of death. In this study 355 admissions of 243 elderly persons with dementia to a purpose built psychogeriatric unit were studied and the mortality rate found to be 8.2%, which is less than that reported elsewhere. Admission for the purpose of respite (holiday) relief is a safe procedure and should not be discouraged. PMID- 2603262 TI - Change in Sunday licensing laws and the effect on Monday absenteeism. A short report on a poultry processing plant. AB - Licensing laws were changed in Northern Ireland on 1st October 1987 to allow drinking of alcohol in public houses on Sundays. The effect on absenteeism was studied in the immediate period after this change using Monday absenteeism as a marker for change. The study was conducted in a small poultry processing plant employing approximately four hundred and forty people. Mean differences between Monday absenteeism for the month of October 1986 and 1985 prior to the change in laws and October 1987 were shown to be not significant. PMID- 2603263 TI - An audit of hospital admissions for acute upper gastrointestinal haemorrhage. AB - A retrospective survey was made of all 189 patients admitted with acute upper gastrointestinal haemorrhage to the Belfast City Hospital in one year. The commonest single reason for admission was peptic ulcer disease, but this was lower than in other published series from the United Kingdom. Overall mortality was 4.8%. The majority of patients did not require either blood transfusion or surgery. There may be potential benefits of endoscopic haemostatic techniques to deal with this condition. PMID- 2603264 TI - Sexual attitudes and practices of selected groups in Northern Ireland since the emergence of AIDS. AB - One hundred and seventeen heterosexual males and females attending a sexually transmitted disease clinic and 57 homosexual males from a local "gay" club were asked to complete a questionnaire regarding their attitudes and sexual practices since the emergence of AIDS. The results show a trend towards increasing partner change rate among heterosexual males. There has been an increase in the practice of insertive anal intercourse by homosexual men with Northern Ireland contacts but no corresponding increase with contacts outside Northern Ireland. The practice of receptive anal intercourse has remained constant. Significant differences in attitudes between homosexual and heterosexual males were expressed with regard to testing of 'at risk groups' (p less than 0.001), in the uptake of testing (p less than 0.01), and in attitudes to sexual practices if they themselves became HIV positive. There was a low level of anxiety amongst heterosexuals regarding risk of HIV infection in the future. Less than 50% of the heterosexual patients attending this clinic use condoms, though more claim to intend to use them in future. PMID- 2603265 TI - The Northern Ireland experience of growth hormone therapy for short stature. AB - In 1967 the first patient in Northern Ireland commenced growth hormone treatment for short stature. By the end of December 1988 a total of 89 patients had been treated. Thirty-two had idiopathic isolated growth hormone deficiency, an incidence of 1.5 new cases per year (in a population of 1.5 million with approximately 30,000 births per year). Since 1967 the mean age at starting treatment has fallen from 18 years to 10 years and the height standard deviation score has fallen from -4.7 +/- 0.6 to -3.4 +/- 0.3. The group with classical growth hormone deficiency (maximum GH less than 7 mU/l during insulin-induced hypoglycaemia) had a greater increase in height velocity over the first year of treatment, 3.8 +/- 0.4 cm, than those with a partial deficiency (maximum growth hormone 7.1 - 20 mU/l), 1.9 +/- 0.4 cm. All pre-pubertal children responded with a rise in the height velocity standard deviation score from -1.8 +/- 0.3 before treatment to +3.5 +/- 0.4 over the first year of treatment. 58% of the adult males and 25% of adult females have attained an adult height within the normal range (3rd centile or above). There have been three deaths, one each from Fanconi's aplastic anaemia which predated growth hormone treatment, an accidental fire injury and a relapsing craniopharyngioma. There have been no deaths from Creutzfeldt-Jakob disease. Growth hormone therapy is safe and effective, but continues to be commenced late in terms both of age and height standard deviation score. PMID- 2603266 TI - Vasectomy reversal. AB - A small personal series of vasovasostomies and a review of the literature on this subject are presented. The importance is stressed of good counselling before vasectomy is undertaken in the first place. PMID- 2603267 TI - Solitary cutaneous leiomyomata: a clinicopathological study of 28 cases. AB - Twenty-eight cases of solitary cutaneous leiomyomata were encountered in a ten year period. They occurred in nine males and nineteen females, the mean age at presentation being 53 years. The lesions occurred most commonly on the lower limbs and 36% were painful. Solitary cutaneous leiomyomata were found to differ from the better known syndrome of multiple cutaneous leiomyomata, in that they did not recur after excision and were not associated with leiomyomata at other body sites. PMID- 2603269 TI - Electroconvulsive therapy and serum potassium. AB - In 54 patients presenting for electroconvulsive therapy, the concentration of serum potassium was measured before and after the induced convulsion modified with a standard anaesthetic technique of methohexitone and suxamethonium. It was found that there was a statistically significant rise in serum potassium, but that the duration of convulsion had no significant effect on that rise in serum potassium. In a further 11 patients, methohexitone alone was administered without ECT, and it was found that serum potassium fell. Methohexitone, suxamethonium and ECT in combination cause a rise in serum potassium which is not clinically important unless pre-induction level is abnormally high, and prolonged convulsion does not exaggerate this rise. PMID- 2603268 TI - Nickel allergy in relationship to previous oral and cutaneous nickel contact. AB - Potential relationships between the development of nickel allergy and previous ear piercing or orthodontic treatment with nickel-containing appliances were studied in 294 patients. We found 77 (31.2%) of 247 patients with pierced ears were allergic to nickel compared to only three (6.4%) patients without pierced ears (p = 0.001), which confirms earlier suggestions that nickel allergy (as assessed by patch testing) is promoted by ear piercing. If orthodontic treatment preceded the event of ear piercing, the frequency of nickel allergy was reduced from 36% to 25%. This supports the view that oral allergenic contacts may induce immunological tolerance. PMID- 2603270 TI - Torsion of the testis revisited. PMID- 2603271 TI - Outcome and benefits of upper gastrointestinal endoscopy in the elderly. AB - Presenting symptoms, physical findings and treatment were reviewed in 70 patients over 65 years old who underwent oesophago-gastro-duodenoscopy in the Royal Victoria Hospital, Belfast, during an 18-month period. Most frequent indications for the procedure were epigastric pain, retrosternal pain or haematemesis. Physical signs were present in only 54%. Abnormal endoscopic findings were detected in 97%. The majority of patients responded to subsequent treatment. It was not possible to identify clinical features associated with major gastrointestinal pathology, which aided selection of those subgroups of elderly patients who would most benefit from endoscopy. PMID- 2603273 TI - Survival after an overdose of Distalgesic (dextropropoxyphene and paracetamol). PMID- 2603272 TI - Pregnancy following in vitro fertilisation of an anonymously donated oocyte in a patient with premature ovarian failure. PMID- 2603274 TI - Concomitant endometrioid carcinoma of the ovary and endometrial carcinoma of the uterus associated with adenocarcinoma in situ of the cervix. PMID- 2603275 TI - Intussusception of the appendix. PMID- 2603276 TI - Incidental enterolithiasis. PMID- 2603277 TI - Late, solitary metastatic renal carcinoma in the pancreas. PMID- 2603278 TI - [Induction of urinary bladder urothelial cancers in the rabbit by dibutylnitrosamine with an artificial bladder calculus as cocarcinogen]. AB - Thirteen rabbits received liquid dibutylnitrosamine (DBN) s.c. at a dosage of 400 mg/kg body weight once a week for a maximum of 16 months to induce transitional cell carcinomas (TCC) of the bladder. In five of these rabbits, 4 months after starting the injection of DBN an artificial stone prepared from a methylmethacrylate 2-component plastic material was implanted into the bladder. Four rabbits developed TCC of the bladder, with latency periods of 15-18 months. These tumors were found in two of the five (40%) rabbits with stones and in two of the eight (25%) rabbits without stones. The stone-bearing animals had more deeply infiltrating tumors, although the tumor induction times were comparable. Within a maximum observation period of 28 months there were no lymphogenous or hematogenous metastases. Another two rabbits showed benign urothelial changes presenting as simple hyperplasia and von Brunn's nests after 4 and 4.5 months, respectively. In two rabbits we found malignant tumors located extravesically, in the lungs and the kidney. The results of our study confirm the feasibility of TCC induction in rabbits by DBN administered s.c. Additional implantation of an artificial bladder stone acting as a co-carcinogen does not lead to a larger number of tumors, but does seem to enhance the degree of TCC induction in the bladder. PMID- 2603279 TI - [Rare kidney tumors]. AB - During the period from 1976 to 1986, a total of 518 kidney tumor patients were treated in the Department of Urology at the University of Freiburg, West Germany. In 34 cases (6.6%) the examination revealed a tumor that was neither a renal cell carcinoma nor a renal pelvic urothelial carcinoma (i.e., a rare renal tumor). Through diagnostic imaging procedures the presence of a tumor was correctly diagnosed in 97% of these 34 cases. Conservative treatment methods were used with 5 patients (4 with renal angiomyolipoma and 1 with hemangioma) whose conditions were clearly diagnosed. In these patients operative therapy was not indicated. The precise histological diagnosis found in 29 patients subjected to surgery was the same as the preoperative diagnosis in only 8 cases (27.6%). Histologically, 20 benign (4 epithelial, 16 mesenchymal) and 9 malignant (3 epithelial, 3 mesenchymal, 3 mixed) tumors were found. The operative methods for rare kidney tumors are the same as those used for the more common kidney tumors. Only in the presence of tumors that are clearly benign, such as angioma or angiomyolipoma, is a wait and see policy with frequent examinations recommended. PMID- 2603280 TI - [Percutaneous treatment of a renal pelvis-calyx cholesteatoma]. AB - A 54-year-old women reported recurrent pain in one side. Radiological and ultrasonographic examination revealed a mass in the left renal pelvis and the lower calyx. With percutaneous calycopyeloscopy keratinous fragments of a cholesteatoma were found and extracted during the same procedure. Up to now, malignant degeneration of a cholesteatoma has never been reported in the literature. Therefore, a conservative surgical treatment is acceptable. PMID- 2603281 TI - [2,8-dihydroxyadenine urinary calculus: the significance of exact physical calculus analysis]. AB - A 21-year-old female patient was treated with Uralyt-U for 3 months for a radiolucent kidney stone. During this therapy the stone increased significantly in volume. After treatment by ESWL, the stone was analyzed by a chemical method and by X-ray diffraction. Calcium phosphate and urate were detected by the chemical method and 2,8-dihydroxyadenine by X-ray diffraction. This case report emphasizes the importance of precise stone analysis for medical treatment is emphasized. PMID- 2603282 TI - [Report of 2 cases of isolated, primary amyloidosis of the male urethra and urinary bladder of a female]. AB - Primary localized amyloidosis of the bladder and urethra is a rare condition. Two cases of isolated primary amyloidosis, of the urethra in a man and of the bladder in a woman, are reported. The clinical specificity of the location and the specific therapy are discussed. We draw attention to the extended, palette of diagnostic investigations now available and the new classification made possible by the introduction of immunohistochemistry and immunoelectron microscopy. PMID- 2603283 TI - [Comment on the contribution by H. Porst and H. van Ahlen. Drug-induced priapism- a report of experiences with 101 cases. Urologe [A] (1989) 28: 84-7]. PMID- 2603284 TI - Prostatic intraepithelial neoplasia (PIN). PMID- 2603285 TI - Prostatic dysplasia: significance in relation to nuclear DNA ploidy studies of prostate adenocarcinoma. PMID- 2603286 TI - Prostatic intraepithelial neoplasia and invasive prostatic adenocarcinoma in cystoprostatectomy specimens. PMID- 2603287 TI - Prostatic intraepithelial neoplasia: detection and correlation with invasive cancer in fine-needle biopsy. PMID- 2603288 TI - Significance of duct-acinar dysplasia in prostatic carcinogenesis. AB - In summary, duct-acinar dysplasia is defined as a one-dimensional continuum of acquisition of malignant morphologic features by the cells lining preexisting ducts and acini. At the far end of the continuum, invasive carcinoma can be demonstrated to arise directly from the walls of dysplastic ducts, leaving no room for doubt concerning the malignant potential of this lesion. The identification of dysplasia in nearly half of prostates without cancer and nearly all prostates with cancer suggests that most adenocarcinomas in the prostate may develop from dysplasia. Dysplasia is further defined as a biologic lesion in which cytoplasmic differentiation is reduced and disordered and the intracellular processing of cytoplasmic proteins and glyco-proteins is altered. Further study of these early biologic changes may yield important insights into the biologic nature of the process of malignant transformation. PMID- 2603289 TI - [Torsion of the appendix with partial thrombosis of the mesentery in a child]. PMID- 2603290 TI - [New principles in classifying vascularized tissue complexes used in plastic and reconstructive surgery]. AB - Based on their personal experience of transplantation of 152 free and 367 non free++ blood-supplied tissue complexes the authors propose to divide them into three main groups in relation to their specific formation and transplantation: mono-, poly- and megacomplexes of tissue (flaps). Distinctions of these three groups of tissue complexes, their general properties as well as indications for their application are discussed. PMID- 2603291 TI - [Errors and complications in the surgical treatment of peptic ulcer]. PMID- 2603292 TI - [The role of daylight on the blood in the mechanism of the therapeutic effect of blood transfusion]. AB - The authors studied the influence of daylight upon peroxidase activity and lipid content in neutrophils by means of cytochemical reactions in blood smears. In the experimental series of studies the blood was taken and stored without daylight. Control blood samples were kept under normal conditions. The studies have shown daylight to be a potent activator of redox processes and lipid metabolism in neutrophils. Similar effect upon peroxidase activity and lipid content in neutrophils is exerted by one calculated dose of long-wave UV rays, two doses inhibiting these processes. Taking and storing blood without daylight contributes to longer valuable morphological and functional condition of the formed elements. PMID- 2603293 TI - [Transfusion of photomodified autologous blood as a method of correcting hypoxemic disorders in surgical patients]. AB - An examination of 24 surgical patients has shown a positive influence of transfusion of photomodified blood upon the partial blood pressure in the arterial and venous blood, oxygen saturation of hemoglobin and arterio-venous oxygen difference. These data evidence the possibility to use the transfusion of photomodified autologous blood for correction of hypoxemia. PMID- 2603294 TI - [Results of truncal and selective proximal vagotomies combined with stomach draining surgery in ulcer-related pyloro-duodenal stenosis]. AB - The authors have shown that remote results of draining operations in combination with truncal vagotomy in ulcerous pyloroduodenal stenosis proved to be similar to results of their combination with selective proximal vagotomy in practically all the parameters. Advantages of the selective proximal vagotomy due to somewhat less amount and less degree of postoperative functional disorders observed after this intervention become practically levelled down by a considerably greater amount of recurrences of ulcers after it as compared with truncal vagotomy and drainage of the stomach. PMID- 2603295 TI - [Results of therapeutic use of plasma- and erythrocytapheresis in patients with arterial thromboobliterating diseases of the extremities]. AB - The article analyzes results of using methods of plasma- and plasmoerythrocytapheresis in 120 patients with occlusive injuries of main arteries of extremities. The efficiency of the methods used both as isolated ones and in combination with surgical procedures in patients with obliterating atherosclerosis, thromboangiitis, and aorto-arteritis of the extremity vessels and the Raynaud disease is estimated. PMID- 2603296 TI - [Intra-abdominal hemorrhage in a patient with hemophilia]. PMID- 2603297 TI - [Clinical evaluation of the effectiveness of acupuncture in surgical patients]. PMID- 2603298 TI - [Ways of reducing postoperative mortality at a department of sanitary aviation]. PMID- 2603299 TI - [Surgical problems of AIDS]. AB - The article presents data on epidemiology of AIDS and on the significance of this infection in surgical practice. PMID- 2603300 TI - [Characteristics of the course of peritonitis in relation to the degree of perforation of the gastrointestinal tract]. AB - An examination and treatment of 80 patients with general forms of peritonitis has shown that the course of the disease is greatly dependent on the character of the bacterial dissemination of the abdominal cavity. A microbiological examination has shown that in all the levels of perforation of the gastro-intestinal tract there are associations of various microorganisms. The most severe course of peritonitis is observed when caused by infection by colonic contents with prevailing anaerobic ++non-clostridial microflora in the exudate. The method of repeated revisions of the abdominal cavity should be used for these forms of peritonitis. PMID- 2603301 TI - [Hepatic insufficiency in patients with peritonitis]. AB - An examination of 14 patients with general forms of peritonitis of different genesis was performed, morphological alterations in the liver tissue and changes of activity of intracellular enzymes of hepatocytes were estimated by groups of living and dead patients. A number of biochemical parameters of the patients' blood plasma were analyzed in parallel. It was established that the development of peritonitis was followed by deep morphological and metabolic disorders. PMID- 2603302 TI - [Increasing the effectiveness of lymphosorption in patients with mechanical jaundice]. AB - Drainage of the thoracic lymph duct and lymphosorption used in 120 patients with mechanical jaundice has reduced the degree of hepatic insufficiency in the preoperative period and improved results of operative interventions. This was especially appreciable in a group of patients with a benign mechanical jaundice. Elimination of toxic substances from the lymph during lymphosorption was greater when using a vibration column, sorbent impregnation by sodium caffeine+-benzoate and ethanol treatment of the lymph. PMID- 2603303 TI - [Medicine and the environment]. AB - Based on an analysis of causes and pathogenesis of pulmonary diseases the author discusses the problem of significance of environmental factors for medicine. He makes a conclusion that "ecological thinking" is necessary for a physician. PMID- 2603304 TI - [Immediate and late results of pancreatoduodenal resection]. AB - Under analysis were results of 22 pancreatoduodenal resections when the Wirsung duct was drained outside. Giving up the previously used pancreaticojejunal+ anastomosis improved the immediate outcomes of the operative treatment although 5 patients died during the nearest period (within 12 days): three of them died of pancreonecrosis. Twelve patients were followed up, 7 of them died, 3 of the rest 5 patients had satisfactory results, 2 patients had good results. PMID- 2603305 TI - [Comparative evaluation of proximal resections in rectal cancer]. AB - The surgical treatment of rectum cancer in 165 patients with the apparatus AKA-2 for compressive anastomoses was analyzed. The oncological adequacy of proximal resections of the rectum at the distal level of the section not less than 3.5-5 cm from the visually seen margin of the tumor depending on its growth type was shown. Low anterior resection of the rectum in patients with considerable size of the tumors is not oncologically justified. PMID- 2603306 TI - [Effect of lumbar sympathectomy on tissue blood flow in the extremities in arteriosclerosis obliterans]. AB - Lumbar sympathectomy in patients with obliterating atherosclerosis of lower extremities in the nearest postoperative period results in acceleration of the intracutaneous blood flow and of intramuscular blood flow as well as in greater extra-tissue blood shunting. At remote terms the intramuscular bloodflow is also accelerated. Patients with the IV degree of ischemia should be divided into two groups according to results of special investigations: patients with traumatic and with ischemic necroses. It is of importance for choice of rational surgical methods and for prognosis of outcomes of the disease. PMID- 2603307 TI - [Pathogenesis of phantom limb syndrome and its treatment]. AB - The spinal mechanism of the phantom pain origin is proved. The underlying factors are: segmentary spinal denervation hypersensitivity and attenuation of the descending inhibitory influence. The pathogenetic treatment of phantom pains is proposed by means of an associated treatment by GABA-ergic drug--Baclofen and alpha-2--adrenomimetic--Clofelin. Good effects of the proposed scheme of treatment confirm the correctness of the presented ideas of pathogenesis of phantom pains. PMID- 2603308 TI - [Epileptic attacks in patients after surgical treatment of recurrent mitral valve stenosis]. PMID- 2603309 TI - [Balloon dilatation of the right coronary artery and permanent atrial electric stimulation in ischemic heart disease complicated by sick sinus syndrome]. PMID- 2603310 TI - [Treatment and prevention of recurrences of stomach cancer]. PMID- 2603311 TI - [Etiopathogenesis and treatment of peptic ulcer]. PMID- 2603312 TI - [Endolymphatic antibiotic therapy in acute appendicitis]. PMID- 2603313 TI - [Acute pansigmoiditis]. PMID- 2603314 TI - [Ways of reducing mortality in injuries of the heart]. AB - Based on an analysis of literature and 45 personal observations the authors make a conclusion that reduction of lethality following wounds of the heart can be reached by introducing certain changes into traditional approaches to the problem. In order to approximate the moment of medical aid to the victims thoracotomy for the liquidation of heart tamponade, arrest of bleeding should be performed at the place of accident or in the admission department of the hospital, even to the detriment of traditional requirements of asepsis. For the prevention and treatment of early and late complications the patients must be directed to specialized centers (thoracal departments of the hospitals). The introduction of counterpulsation of the aorta, pacemakers, auxiliary blood circulation should be considered as requirements of time. PMID- 2603315 TI - [Autotransplantation of splenic tissue after splenectomy]. AB - The authors have performed heterotopic autotransplantation of the spleen tissue into the greater omentum pocket as a suspension or tissue sections in 14 patients with emergency splenectomies. The method of autotransplantation is described. No complications resulting from autotransplantation were noted. PMID- 2603316 TI - [Diagnosis of spinal fractures using optical processing of the roentgenologic image]. AB - X-ray examinations by a traditional method in 694 patients with non-complicated compression fractures in the thoraco-lumbar part of the vertebral column do not always give the exact picture of the character of fractures of the vertebral column. The method of optic processing the roentgen picture was used in 30 patients for more detailed analysis of structural changes in the vertebrae bodies. The method allowed to specify structural changes in the vertebra bodies, including the detection of the fracture plane, abruption of a body portion, detection of an additional contour of the limiting plate in its pressing into the vertebra body and the zone of infiltration in the upper portions of the body. PMID- 2603317 TI - [Characteristics of morphologic diagnosis of malignant transformation of chronic duodenal ulcer during its surgical treatment]. AB - Under investigation were results of gastric biopsies, tissues of ulcers dissected during operation and findings of an analysis of preparations in paraffin sections. Findings of all the three diagnostic methods were shown to be completely identical in 63 patients (chronic ulcer in 54 of them, malignant ulcer -in 9). Errors took place in 17 patients. Causes of the errors are discussed. Practical recommendations are given. PMID- 2603318 TI - [Gunshot neck wounds penetrating the oral cavity and pharynx, associated with cranio-cerebral injuries]. PMID- 2603319 TI - [Replantation of the arm with using intraoperative hemosorption]. PMID- 2603320 TI - [Postoperative disorders of the hemostasis system in children]. AB - Under examination there were 100 healthy children and 407 children operated upon for different surgical diseases. An analysis of 1585 electrocoagulograms was performed with a computer. New integral parameters of hemostasis were developed. Their quantitation is given in norm and pathology. A new classification of the disseminated intravascular coagulation syndrome and corresponding schemes of treatment of alterations in the hemostasis system are proposed. PMID- 2603321 TI - [Postoperative rehabilitation of children with Hirschsprung disease]. AB - Under study were remote results in 174 patients with Hirschsprung's disease operated upon by the method of Soave-Lyonyushkin. Among functional disturbances the patients had considerably decreased pressure in the anal canal, change of threshold parameters of the recto-anal reflex showing disturbed neuro-reflectory connections of the newly-formed rectum with the sphincter system. The restorative period after operation was considerably shorter due to purposeful curative prophylactic measures which are necessary to be started from the very early postoperative period. The developed scheme of rehabilitation of patients after surgical treatment of Hirschsprung's disease is fairly effective which is demonstrated by high level (96.5%) of good and excellent long-term results. PMID- 2603322 TI - [Benign tumor of the gallbladder in a child]. PMID- 2603323 TI - [Non-parasitic cysts of the spleen in children]. PMID- 2603324 TI - [Acute appendicitis and torsion of the greater omentum in a child]. PMID- 2603325 TI - [Torsion of the appendix in a child]. PMID- 2603326 TI - Transitional cell carcinomas of the urinary tract in a colony of beagle dogs. AB - Gross and light microscopic features of transitional cell carcinomas (TCC) of the urinary tract were examined in Beagle dogs used for the study of the long-term effects of low-dose, whole-body, 60Co gamma radiation. Thirty-eight cases of TCC occurred among 990 dogs that were from 0 to 14 years of age. There was no conclusive evidence of a radiation effect. The 38 TCC were equally divided between male and female dogs, but there was a significant difference in the sex distribution of urethra-origin TCC. Eleven males had a primary urethral TCC compared to only two females. There was no significant difference between the urethra-origin and bladder-origin TCCs in the number of tumors that caused clinical signs, metastasized, or that contributed to the death of the dog. All cases of urethral TCC in male dogs occurred in the prostatic urethra. The majority of these cases were not recognized to be neoplasms at gross necropsy, but microscopic examination revealed the TCC. Our findings differ from previous reports stating that TCC occurs more frequently in female than male dogs, and they especially differ from reports claiming that urethra-origin TCC is predominantly a disease of female dogs. PMID- 2603327 TI - Effect of chronic administration of recombinant bovine tumor necrosis factor to cattle. AB - Cachectin/tumor necrosis factor-alpha (TNF), a protein produced by macrophages upon stimulation, has been implicated as an important mediator of inflammatory processes and of clinical manifestations in chronic infectious diseases. In order to study further the potential role of TNF in infectious diseases, a homologous system was employed in which recombinant Escherichia coli (E. coli) derived bovine TNF (rBoTNF) was injected in cattle, either as a single bolus or in a repetitive treatment-regime. No clinical signs were observed, although changes occurred in hematologic and immunologic parameters when less than 0.5 mg of TNF/100 kg body weight was administered twice daily for 18 days. Prolonged treatment with 0.05-0.5 mg/100 kg induced histologic but no gross changes in the kidneys and liver. When doses were increased above 0.5 mg/100 kg, depression, anorexia, cachexia, and diarrhea appeared rapidly. Pathologic changes were apparent in various tissues including liver, kidneys, and lymphoid organs; body fat depots were depleted. Most of these changes appeared to be reversible; return to normal tissue-morphology occurred within 3 weeks of withdrawal of rBoTNF. The clinical and pathologic changes induced by prolonged rBoTNF administration resembled those observed in some chronic parasitic and viral infections of cattle in which macrophage-activation characteristically occur. Our finding may be relevant to the elucidation of the pathogenesis of these and other chronic infections. PMID- 2603328 TI - Emperipolesis of hematopoietic cells within megakaryocytes in bone marrow of the rat. AB - Emperipolesis of hematopoietic cells within megakaryocytes was found in rats. The incidence was less than 0.3% in young rats (2 to 12 months old) but increased to 2-5% among the aging rats (18 to 24 months old). The incidence increased markedly in hyperplastic bone marrow secondary to chronic suppurative or neoplastic lesions. Mature neutrophils appeared to be the most common marrow cell engulfed by megakaryocytes. By light microscopy, engulfed cells were separated from megakaryocyte cytoplasm by a narrow pericellular space. By electron microscopy, marrow cells engulfed by megakaryocytes were located in the open canalicular system. Cell membranes of both engulfed cells and megakaryocytes were intact, and there was no fusion of cell membranes or phagosome formation in the megakaryocytes. PMID- 2603329 TI - Histopathologic findings and energy dispersive X-ray spectroscopic analysis of experimentally induced foreign-body pneumonias in rats. AB - To document the diagnostic features of foreign-body pneumonias, four commonly used orally administered medicaments were instilled into the lungs of Sprague Dawley rats. Rats in each group received a single 0.4 ml dose of either barium sulfate suspension (BaSO4), mineral oil, Pepto-bismol, or Kaopectate inoculated into a lung via a mainstem bronchus. The other lung served as a non-inoculated control. Rats were euthanatized on post-inoculation day 2 or 7 in order to document fully-developed acute pulmonary lesions and developing, chronic pulmonary lesions, respectively. Light microscopic features of BaSO4-inoculated lungs were distinctive from changes in mineral oil-inoculated lungs at both post inoculation days. On post-inoculation day 2, rats inoculated with BaSO4 had pneumonia characterized by large numbers of alveolar macrophages containing green to-brown granular material. There was minimal interstitial involvement. On post inoculation day 2, mineral oil caused pneumonia characterized by giant cells and alveolar macrophages that had cytoplasms distended with variably-sized clear vacuoles. Lungs inoculated with BaSO4 or mineral oil had changed little on post inoculation day 7 compared to the light microscopic features observed on day 2. On post-inoculation day 2, rats inoculated with either Pepto-bismol or Kaopectate had broncho-interstitial pneumonia with areas of necrosis and hemorrhage. On post inoculation day 7, lungs inoculated with Pepto-bismol or Kaopectate had extensive fibrosis within alveolar lumens. Energy dispersive spectroscopy performed on sections of lung from rats given BaSO4, Pepto-bismol, and Kaopectate yielded a unique elemental spectrum for each compound in situ on post-inoculation days 2 and 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2603330 TI - Clinicopathologic characterization of canine juvenile cellulitis. AB - The syndrome of canine juvenile cellulitis was observed and characterized throughout its clinical course when it occurred spontaneously in a litter of dogs. Histologically, pyogranulomatous inflammation was seen in facial skin and mandibular and superficial cervical lymph nodes of affected dogs. The predominant inflammatory cell characterized by light and electron microscopy and by immunohistochemical staining was an epithelioid macrophage. The same pyogranulomatous inflammatory process was seen in a lymph node anatomically distant from the site of apparent disease. Interestingly, a littermate with neither clinically evident dermal lesions nor lymphadenopathy had histologic evidence of a milder, but similar inflammatory process in a mandibular lymph node. The observation of canine juvenile cellulitis in clusters of dogs between 1 and 4 months of age and its apparent systemic nature suggest an infectious etiology. Bacterial, fungal, or viral agents were not isolated from affected lymph nodes. Attempts to transfer the disease by inoculation of neonatal puppies with tissue from affected dogs were also unsuccessful. PMID- 2603331 TI - Dyspnea in aging rats due to disseminated intravascular coagulation (DIC). AB - During an 18-month oncogenicity study using rats, approximately 10% of the animals developed a form of respiratory distress very similar to that seen in the terminal stages of chronic respiratory disease, commonly associated with Mycoplasma pulmonis infection. Investigation of the lungs of the affected rats revealed not only that they did not have the consolidation usually associated with chronic respiratory disease, but they also appeared macroscopically normal. Further investigation of a number of cases revealed systemic intravascular thrombus formation of the type usually referred to as disseminated intravascular coagulation. Using an antiserum to fibrin we have demonstrated the presence of intravascular fibrin deposits in the lungs of the affected rats and have shown them to be the same as experimentally induced intravascular fibrin deposits induced in rat lungs by the administration of thrombin after blocking the fibrinolytic system. This is the first example of such a phenomenon being recorded in aging rats. PMID- 2603332 TI - Canine bilateral extraocular polymyositis. PMID- 2603333 TI - Proliferative colitis in ferrets: epithelial dysplasia and translocation. PMID- 2603334 TI - Unilateral optic nerve aplasia in two young Slc:Wistar rats. PMID- 2603335 TI - Cytologic, histologic, and ultrastructural characteristics of a canine myxoid liposarcoma. PMID- 2603336 TI - Malignant canine anterior uveal melanoma. PMID- 2603337 TI - Accuracy of prediction of the liveweight of horses from body measurements. AB - Fifty-three horses, all but two of them over two years of age and varying in type, sex and liveweight (230 to 707 kg) were weighed and seven different body measurements were recorded in duplicate by a single operator. The best overall prediction of liveweight using an equation with two variables was found to be: liveweight (kg) = (umbilical girth [cm])1.78 X (length of body from tuber ischii to elbow [cm]0.97/3011). This equation had an adjusted R2 value of 94.9 per cent and was derived from the pooled data, because differences of sex, type and weight did not significantly affect the relationship. The stable behaviour of the relationship was demonstrated by the fact that about 95 per cent of the residuals lay within +/- 53 kg, giving an average error of 4.7 per cent. The accuracy of prediction of the equation was better than the accuracy of four other established equations. A nomogram based on the equation is given. PMID- 2603338 TI - Doses for unlicensed medicines. PMID- 2603339 TI - Drugs for pigeons. PMID- 2603340 TI - Infrared thermography for detecting sweet itch. PMID- 2603341 TI - Intramammary infections. PMID- 2603342 TI - Zinc deficiency by any other name... PMID- 2603344 TI - Fear in animals. PMID- 2603343 TI - Second opinions. PMID- 2603345 TI - Behaviour of cows in cubicles and its possible relationship with laminitis in replacement dairy heifers. AB - The behaviour of cows in cubicles was studied in two dairy herds which were under the same ownership and had similar buildings and management systems. One of the herds had an annual problem of lameness due to laminitis leading to solar ulceration in the replacement first lactation heifers. There were considerable behavioural differences between the cows in the two herds. In the problem herd the heifers and cows stood for significantly longer, more heifers were seen not to use the cubicles, and there were more examples of aberrant behaviour than in the other herd. Less straw was used for cubicle bedding in the problem herd and when the amount used was increased to one bale per 10 cows per day no new cases of laminitis and solar ulceration occurred in the heifers. PMID- 2603346 TI - New controls on substances hazardous to health. PMID- 2603347 TI - Mite infestation. PMID- 2603348 TI - Efficacy of anthelmintics in horses. PMID- 2603349 TI - Clinical haemobartonellosis associated with use of corticosteroid. PMID- 2603350 TI - Competitive exclusion--Salmonella in poultry. PMID- 2603352 TI - Dog registration. PMID- 2603351 TI - Training as an aid to welfare. PMID- 2603353 TI - Influence of androgens on the genital tract of cyclic heifers. AB - Cyclic heifers were implanted with the synthetic androgen trenbolone acetate (TBA = 17 beta-hydroxy-19-norandrosta-4, 9, 11-trien-3-on-17 beta-acetate, C2OH2403) (for formulas see Fig. 1). The influence of this androgen on the macroscopic and microscopic morphology of the genital tract was studied. The most striking result was the induction of polycystic ovaries. The clitoris was markedly enlarged and the cervix showed an increased amount of mucus. Microscopically, extensive folding of the cervical epithelium, consisting of tall swollen columnar cells with basal nuclei was seen. The vagina showed an increase of PAS-positive granules in the superficial layer of the epithelium, while there was no increase in the height of the epithelium. These effects are due to androgenic influence on the female genital tract and are in no case specific to one particular product. They could be of help in the detection of the illegal use of agents with androgenic activity. PMID- 2603354 TI - Delay in timing of the oxfendazole pulse release bolus in calves in The Netherlands. AB - The efficacy of the oxfendazole pulse release bolus (OPRB) was tested in a grazing experiment at the University of Utrecht. Three groups of four OPRB treated calves and one group of four untreated control calves were grazed on separate pastures between 18 May and 21 October 1987. Based on faecal egg counts for strongyle-type eggs and Nematodirus eggs, embryonation of Nematodirus eggs and faecal larval counts for lungworm, the first pulse of oxfendazole was released after 28 to 63 days, which was later than the period of approximately three weeks indicated by the manufacturer and others. As far as could be detected, the second to fifth pulses were not as delayed, but generally the three week period was also exceeded. This delayed release of the pulse resulted in a build-up of pasture infectivity for gastrointestinal nematode larvae and lungworm larvae. Nevertheless, this did not result in clinical gastrointestinal helminthiasis and husk in the treated groups of calves, whereas severe husk and mild gastrointestinal helminthiasis were seen in the control group. PMID- 2603355 TI - Intravenous catheterisation of conventional pigs without application of antimicrobial agents. AB - In six experiments 43 castrated male conventional pigs weighing 25-41 kg were catheterised by inserting a cannula via the jugular vein into the cranal caval vein. The catheters were taped to the spinal neck region where the tap stops were located. Antimicrobial agents were not applied. One pig died 32 hour after surgery from Porcine Stress Syndrome. The catheters remained patent for at least nine days in 38 of the remaining 42 animals (90%). In two animals the catheter by mistake was not inserted into the jugular vein. Two animals got catheters with a one-way blockage four days after surgery. In these animals autopsy revealed thrombosis and phlebitis of the occluded vein and a valve-like thrombus at the tip of the catheters. In seven of the 43 pigs the effects of anaesthesia, surgery and catherisation were followed using rectal temperature and haematological and some blood biochemical parameters for nine days after the surgery. It is concluded that this catheterisation technique, without application of antimicrobial agents, can be used well for experimental infections and pharmacokinetic studies. PMID- 2603356 TI - Oral absorption and bioavailability of flumequine in veal calves. AB - The oral absorption and bioavailability of flumequine was studied in 1-, 5- and 18-week-old calves following intravenous and oral administration of different formulations of flumequine (Flumix, Flumix C and pure flumequine). Increasing age had a negative influence on the Cmax after the administration of Flumix, based on a larger VD in the older calves. The Cmax decreased from 5.02 +/- 1.46 micrograms/ml in the first week to 3.28 +/- 0.42 micrograms/ml in the 18th week. Adding colistin sulfate to the flumequine formulation and administring pure flumequine mixed with milk replacer had a negative effect on the Cmax of flumequine after oral administration of 5 and 10 mg/kg body weight. The bioavailability of the orally administered flumequine formulations was 100% in all cases except after the administration of Flumix C, for which it was 75.9 +/- 18.2%. The urinary recovery of flumequine after intravenous injection of a 10% solution varied from 35.2 +/- 2.3% for Group B, to 41.2 +/- 6.3% for Group C. The dosage of 5 mg/kg body weight Flumix twice daily in 1-week-old veal calves is sufficient to reach therapeutic plasma concentrations, based on a MIC value of 0.8 micrograms/ml of the target bacteria. In older calves it is advisable to increase the dosage 7.5 or 10 mg/kg body weight every 12 hours. In combination with colistin sulfate it is also advisable to increase the dosage slightly because of the negative effect of the colistin sulfate on the Cmax of flumequine. PMID- 2603357 TI - Nonlinear pharmacokinetics of intravenous sulphadimethoxine and its dosage regimen in pigs. AB - The time courses of the total (Ct) and unbound plasma (Cf) concentration after the i.v. injection of 20, 50 and 100 mg/kg of sulphadimethoxine (SDM) were examined in pigs. The area under the Ct-time curve per unit dose decreased dose dependently. Vdarea and total body clearance of Ct increased dose-dependently. The concentration-dependent plasma protein binding of SDM was evident after 50 and 100 mg/kg. The time courses of Cf en Ct after 3 doses were analyzed by a one compartment open model with nonlinear plasma protein binding. The agreement between calculated curves of Cf and Ct and the observed values, and relative constancy of pharmacokinetic parameters were obtained over 3 doses. These results suggested that the nonlinear pharmacokinetics of SDM was caused by saturable plasma protein binding. The multiple i.v. dose of SDM was based on the dosage regimen using the nonlinear pharmacokinetic model (50 mg/kg, 24 hour interval, 4 days). The observed Cf was maintained in the intended range by the dosage regimen. Therefore, the dosage regimen based on the nonlinear pharmacokinetics may allow the unbound concentration after i.v. injection of SDM in pigs to be controlled. PMID- 2603358 TI - A severe outbreak of respiratory tract disease associated with bovine respiratory syncytial virus probably enhanced by vaccination with modified live vaccine. AB - A severe outbreak of respiratory tract disease associated with bovine respiratory syncytial virus (BRSV) on a large beef-fattening farm is described. The outbreak started two days after five- to seven-month-old calves were vaccinated with a modified live BRSV vaccine. The disease ran a very severe course among five- to seven-month-old vaccinated calves, but disease was absent in eight-month-old an older non-vaccinated calves. The presence of IgM antibodies in sera of non vaccinated calves indicated that BRSV was spreading on the farm between two to 15 days before the day of vaccination. The data indicate that vaccination with modified live vaccine during the course of a natural infection may enhance the severity of disease. The possible pathogenesis of the disease is discussed. PMID- 2603359 TI - Hysterectomy during the luteal period in dogs chronically treated with bromocriptine. AB - To determine whether prolactin has luteolytic properties during the first part of the luteal period, hysterectomy was performed in four dogs, in which prolactin had been chronically suppressed by bromocriptine administration. The concentration of progesterone in the peripheral blood decreased upon hysterectomy during the first part of the luteal phase and regained normal values after about seven days. The progesterone patterns during the perisurgical period in these dogs were similar to those patterns observed in dogs hysterectomised without bromocriptine treatment. It is concluded therefore that, in the dog, luteolytic properties can not be attributed to prolactin. PMID- 2603361 TI - Hypothermia protects brain function in acute carbon monoxide poisoning. AB - The role of body temperature in the morbidity and mortality resulting from acute severe carbon monoxide (CO) poisoning (2400 ppm CO, 90 min) was investigated using an unanesthetized animal model. Modified Levine prepared female rats (left common carotid artery and jugular cannulated) displayed a lower rate of recovery period (4 hr) re-warming, and an increased mortality rate and behaviorally assessed neurologic index (NI) compared to normal rats. This indicated their greater susceptibility to CO hypoxia, although the degree of CO-induced hypothermia was the same in both groups. The whole-body cooling of Levine rats to a similar extent prior to CO exposure increased somewhat the post-CO re-warming rate, and marginally decreased NI and mortality during CO exposure (in-CO). In contrast, maintenance of constant body temperature by external heating during CO exposure resulted in a negative post-CO re-warming rate and sharply increased NI and in-CO mortality. Normal euthermic rats were much less severely affected by CO. The results suggest that hypothermia, whether CO-induced or produced by prior cooling, provides measurable protection of brain function during acute severe CO poisoning, and that maintenance of body temperature increases in-CO mortality and interferes with ability to thermoregulate and increases NI in survivors. PMID- 2603360 TI - Relay bioavailability and toxicity of isometamidium residues: a model for human risk assessment. AB - The bioavailability and potential toxicity of the residues of the antitrypanosomal drug isometamidium (ISMM) in bovine tissues were investigated in male Sprague-Dawley rats. They were allowed to feed for 7 and 21 days on a standard diet, to which were added lyophilized tissues from a calf treated im with a combination of 45 mg 14C-ISMM and 73 mg unlabelled ISMM (1 mg/kg bodyweight). Cumulative excretion of radioactivity of the residues in feces of the rats was on average 90% of the dose. No radioactivity was detectable in the tissues examined, including the kidney, liver, spleen, muscle, stomach and small intestine. No clinical effects were seen in any of the rats, and both gross and histopathological examinations did not reveal any lesions. In rats given 14C-ISMM (2.245 mg/kg bodyweight) by oral gavage, cumulative excretion of radioactivity in feces after 48 hr amounted to about 93% of the dose, and no radioactivity was detectable in tissues. Similarly, none of the rats showed any clinical effects and no gross lesions were seen at necropsy. This study shows that ISMM residues are not significantly bioavailable and exhibit no subchronic toxicity. PMID- 2603362 TI - Cantharidin content of two species of Oklahoma blister beetles associated with toxicosis in horses. AB - Cantharidin content of male and female Epicauta occidentalis and E conferta was determined. Aspects of the life cycle of blister beetles, taxonomy, pheromonal and adaptive functions of cantharidin relative to the medico-legal aspects of cantharidin poisoning, prevention and control in horses are discussed. PMID- 2603363 TI - Myoglobinemia and renal failure in toluene poisoning: a case report. AB - Rhabdomyolysis, myoglobinemia and acute renal failure were observed in a 26-year old male after oral ingestion of a solvent containing toluene. The rhabdomyolysis and myoglobinemia seemed to be related to the toxicity of toluene as well as the patient's violent attempts to escape restraint. It is likely that acute renal failure, in this patient was not due to myoglobinemia alone, but also to renal toxicity of toluene. PMID- 2603364 TI - Sulfur (hydrogen sulfide) toxicosis in cattle. PMID- 2603365 TI - Fatal poisonings by copper sulfate ingested from "spiritual water". PMID- 2603366 TI - Effects of repeated high dose administration of recombinant bovine somatotropin in lactating dairy cows. AB - Four multiparous Holstein cows were utilized to determine the effects of high doses of recombinant bovine somatotropin (rbSt) on milk production, feed intake, somatotropin concentration in milk, blood and urine constituents and the presence or absence of treatment-related lesions. Treatments were 0 (control) or 430 mg rbSt daily for 21 days as im injections beginning approximately 150 days into lactation. Cows were fed concentrate according to level of milk production and corn silage ad libitum. Milk yield of rbSt-treated cows increased 34% while dry matter intake and net energy intake decreased. Serum and milk bSt concentrations were elevated following treatment. Red blood cell count, hemoglobin, and hematocrit decreased in rbSt-treated cows; however, values remained within the normal range. Blood urea nitrogen concentration was decreased following treatment. Serum alkaline phosphatase activity, insulin and glucose concentrations were increased in 1 treated cow. No changes were observed in serum thyroxine, cortisol or bSt antibody concentrations. Evidence of irritation at the injection site was examined microscopically and was consistent with irritant swelling. Fetuses of rbSt-treated cows were normal, and cows did not abort. No serious adverse effects were observed following daily injections of 430 mg rbSt. PMID- 2603367 TI - Actions taken by The American Association of Poison Control Centers Board of Directors at midyear meeting April 6-7, 1989 Tucson, Arizona. PMID- 2603368 TI - Brunfelsia pauciflora ("yesterday, to-day and tomorrow") poisoning in a dog. PMID- 2603369 TI - Nickel and nickel-conjugate metabolism and acute toxicity. PMID- 2603370 TI - Abdominal adhesions after small intestinal surgery in the horse. AB - One hundred thirteen of 172 horses (66%) undergoing exploratory celiotomy for a small intestinal lesion survived 4 or more days after surgery. Intra-abdominal adhesions causing clinical problems requiring additional surgery or euthanasia were documented in 25 horses (22.1%). Problems developed in significantly more males than females. The most common initial small bowel lesion was ileal impaction (12 horses); 21 horses underwent small intestinal resection or bypass. However, there was no significant difference in the incidence of intra-abdominal adhesions between horses that underwent intestinal resection or bypass and those that did not. Only 4 of the 25 horses (16%) with problems associated with postoperative adhesions survived. The mean interval between surgical procedures or between the initial procedure and euthanasia for all horses was 84 days (range, 7-512 days; median, 25 days). However, 70% of the subsequent celiotomies were performed within 60 days of the previous surgery. The mean interval between celiotomies was 221 days (range, 9-512 days) for the survivors and 61 days (range, 7-358 days) for the nonsurvivors. These results indicated that most of the problems related to postoperative intra-abdominal adhesions occurred within 2 months of the initial small intestinal surgery. Furthermore, the earlier development of postoperative adhesions was associated with a poorer prognosis for survival. PMID- 2603371 TI - Survival after small intestine resection and anastomosis in horses. AB - The authors examined factors influencing survival in 140 horses that recovered from anesthesia after small intestinal resection between 1968 and 1986, using Kaplan-Meier estimated survival curves and the Cox proportional hazards regression model. Seventy-two horses (51%) died during the initial postoperative period, 19 horses (14%) died after discharge from the hospital, 33 horses (24%) were alive, and 16 horses (11%) were classified as censored. Mean age at surgery was 8 years. Horses 15 years of age or older, Arabians and Stallions, were overrepresented in the hospital population. The most common reason for resection was strangulation of bowel through a mesenteric rent. The mean and 50% median survival times were 1540 and 27 days, respectively. Horses admitted after January 1, 1980, had a significantly longer survival than those admitted before that time. Survival was longer after anastomosis of two small intestinal segments than after anastomosis of a small intestinal segment to the cecum; however, the length of bowel resected and the method of anastomosis had no demonstrable influence on survival. Of the variables studied, the heart rates at presentation and 24 hours after surgery were the most accurate predictors of survival. PMID- 2603372 TI - Retrospective evaluation of repeat celiotomy in 53 horses with acute gastrointestinal disease. AB - Fifty-three of 648 horses (8.2%) treated surgically for acute gastrointestinal obstruction were subjected to repeat celiotomy. Forty horses (75%) recovered from anesthesia after repeat celiotomy, and 26 horses (49%) were discharged from the clinic. Excluding two horses lost to follow-up, 10 of 51 horses (20%) survived long term. Horses subjected to repeat celiotomy had a significantly lower long term survival rate than horses subjected to a single celiotomy. Twenty-eight horses had mechanical obstructions, and 22 had functional obstructions at the second surgery. Significantly more horses with mechanical obstructions recovered from anesthesia, but there was no difference in short-term or long-term survival. Seventy-seven percent of horses were subjected to two celiotomies without being discharged from the clinic between procedures. The intervals between primary and repeat celiotomies ranged from less than 24 hours to 4 years, with 89% of them being less than 2 months. Horses with functional obstructions at the second surgery had a significantly shorter interval between surgeries than horses with mechanical obstructions. Twenty-three horses had sequelae of the primary celiotomy, 19 had progression of their original disease, 8 had recurrence of the same condition, and 3 had unrelated problems. Intestinal ischemic necrosis was the most common diagnosis at repeat celiotomy, and small intestinal obstruction by adhesions was the second most frequent. PMID- 2603373 TI - Esophageal replacement in the dog by microvascular colon transfer. AB - An orthotopic colon graft based on the middle colic artery and vein was implanted with microvascular technique and a stapling instrument in five dogs. The grafts were successful in four dogs. A similar colon autograft was used to replace the entire thoracic esophagus in five dogs. The recipient vessels were the left carotid artery and left external jugular vein. Four of the grafts failed because of kinking and thrombosis of the arterial supply (2 dogs) or the venous outflow (2 dogs). One graft, which had a viable vascular supply, developed a severe leak at the colon-to-stomach anastomosis, and the dog was euthanatized on day 3. The recipient vascular pedicle was modified and used successfully to replace a portion of the cervical esophagus in three dogs. The grafts survived, the dogs could swallow liquids and semisolid food well, and, at necropsy after 4 weeks, the anastomotic sites were well healed. The graft sites contained essentially normal colon mucosa. PMID- 2603374 TI - Ventral rhinotomy in the dog and cat. AB - The nasal cavities of 14 dogs and three cats were explored surgically using a ventral rhinotomy. The exposure achieved through this approach was considered to be equal to a dorsal rhinotomy. One animal died during the immediate postoperative period from perforation of a gastric ulcer. The other animals recovered well and had no significant complications. The long-term survival of the animals was consistent with previous reports for their diseases. Ventral rhinotomy is no more difficult than dorsal rhinotomy, has less patient morbidity and fewer postoperative complications, and is more cosmetically acceptable. PMID- 2603375 TI - Vulvovaginectomy and perineal urethrostomy for neoplasms of the vulva and vagina. AB - Vulvovaginectomy and perineal urethrostomy were performed in three dogs with extensive neoplasms of the vulva and vagina. One benign tumor (fibroleiomyoma) and two malignant tumors (transitional cell carcinoma and anaplastic spindle cell sarcoma) were diagnosed. Survival times were 9 weeks to 10 months. Urinary continence was preserved in all three dogs. The procedure may be curative for benign tumors or malignant tumors that have not yet metastasized; it is a palliative procedure for advanced malignancies. PMID- 2603376 TI - Nuclear medical bone imaging and targeted radiography for evaluation of skeletal neoplasms in 23 dogs. AB - Nuclear medical bone imaging was used in combination with targeted radiography to detect metastatic or multicentric lesions in 23 dogs with skeletal neoplasms. Each dog with a radiographically diagnosed skeletal neoplasm was injected with Technetium-99m labeled methylene diphosphonate (99mTc-MDP) (15.0 mCi intravenously) for whole body imaging. All areas with increased uptake of 99mTc MDP were radiographed. In 19 dogs, the amount of bone shaft involvement in primary sites indicated by bone imaging was larger than the amount indicated by radiography. Eighteen dogs had secondary areas of increased 99mTc-MDP uptake, six of which had secondary areas that were suspected radiographically to be neoplastic. Four dogs had lesions characterized histologically as neoplasia, one as bone infarction and one as normal cortical bone. Positive predictive value for this strategy was 66.7%. Results of this study suggest that nuclear medical bone imaging with targeted radiography is a quick, noninvasive technique with a good positive predictive value for evaluation of the skeleton for metastatic or multicentric sites of neoplasia. PMID- 2603377 TI - System behavior of commonly used cranial cruciate ligament reconstruction autografts. AB - Biomechanical analysis was performed on the cranial cruciate ligament (CCL) and three autogenous tissues used for CCL reconstruction in the canine stifle. The autogenous tissues were patellar ligament-based autografts described for over-the top CCL replacement and included the central one third of the patellar ligament, the medial one third of the patellar ligament, and the lateral one third of the patellar ligament with fascia lata. Tension testing produced abrupt failure of the central and medial autografts but sequential failure of the lateral autograft. Structural properties were determined for the overload condition and within the load range of normal activity for the CCL (physiologic range). None of the autograft systems approached the stiffness, maximum load, and energy absorbed to maximum load of the CCL. The central and lateral autografts were stiffer, had greater maximum loads, and absorbed more energy to maximum load than the medial autograft. The central and lateral autografts had an elastic range, as defined by proportional limit, which corresponded to the physiologic range of loading for the CCL. Loads that corresponded to physiologic displacement of the lateral and central autografts were near the maximum load of the fixation site, which underscored the need for postoperative support of the repaired stifle. PMID- 2603378 TI - Production of patellar lesions by medial patellar desmotomy in normal horses. AB - Medial patellar desmotomy was performed on one (treated) hindlimb, and a sham operation on the other (control) hindlimb, of 12 normal horses. The horses were examined for lameness before medial patellar desmotomy and at months 1, 2, and 3. The femoropatellar joints were examined radiographically and arthroscopically at month 3. All horses were lame on the treated limb at months 1, 2, or 3. Radiographic changes, including fragment formation at the distal aspect of the patella and bone production at the attachment of the middle patellar ligament on the patella, were present in 11 horses at month 3. Articular cartilage fibrillation or detachment was seen arthroscopically on the patellas of all treated limbs. In six horses, loosely attached fragments of bone and cartilage were removed arthroscopically from the distal aspect of the patella of the treated limb. The control limbs were clinically, radiographically, and arthroscopically normal throughout the study. Medial patellar desmotomy results in pathologic changes in the articular cartilage of the patella and adjacent soft tissues. Use of this surgical procedure should be reserved for persistent and confirmed cases of upward fixation of the patella. PMID- 2603379 TI - Postanesthetic equine myopathy suggestive of malignant hyperthermia. A case report. AB - Signs of malignant hyperthermia, including progressive increases in PaCO2, skin temperature and heart rate, and elevated serum levels of potassium, inorganic phosphate, and creatine kinase, were identified in a halothane-anesthetized horse. Treatment was discontinuing halothane administration, applying ice and cold fluids, and hyperventilating with 100% oxygen. After an initial recovery, bilateral hindlimb myopathy and pigmenturia developed. The myopathy resolved after treatment with oral dantrolene, IV fluids, and hydrocortisone. Results of caffeine-halothane challenge, using semimembranosus muscle collected 2 weeks after the episode, were considered within normal limits for horses. The intraoperative abnormalities were evidently predictive of postanesthetic myopathy but the cause in this horse remained unclear. PMID- 2603380 TI - Suspected malignant hyperthermia after halothane anesthesia in a cat. AB - A 6 month old domestic shorthaired cat died of suspected malignant hyperthermia. Anesthesia was induced and maintained with halothane vaporized in oxygen and nitrous oxide, after acepromazine premedication. Before an incision was made, the cat's heart rate dropped from 140 to 90 beats/min concomitant with a drop in blood pressure. Glycopyrrolate administration resulted in severe ventricular tachycardia (340 beats/min). Halothane and nitrous oxide were discontinued and the surgery was abandoned. Lidocaine administration resulted in a normal sinus rhythm. In recovery, the cat was tachypneic and struggling, with a rectal temperature of 40.1 degrees C that quickly increased to 41.4 degrees C. While the cat was being cooled, cardiac dysrhythmias progressed to ventricular fibrillation that was not responsive to cardiorespiratory resuscitation. Blood specimens obtained while the cat was being cooled showed hyperkalemia (10.0 mEq/L) and increased serum creatine kinase activity (780 IU/L). There was extreme extensor rigidity (rigor mortis) within 5 min of cardiac arrest. Results of microscopic and electron microscopic examination of muscle showed occasional perivascular infiltrates of lymphocytes with infrequent perimysial and epimysial neutrophils and a few sarcomeres with streaming of Z-bands (suggesting a contracted state). Histochemical evaluation of skeletal muscle showed no significant difference between type I and type II fibers. PMID- 2603381 TI - Characterization of surface markers of bovine gut mucosal leukocytes using monoclonal antibodies. AB - The surface phenotypes of bovine intestinal leukocytes isolated from the intraepithelium (IEL), lamina propria (LPL) and Peyer's patches (PPL) of the small intestinal mucosa of normal adult cows were determined using monoclonal antibodies (mAb) specific to adult bovine peripheral blood leukocytes (PBL). Laser flow cytometric (LFC) analysis demonstrated that IEL contained significantly (P less than 0.1 to 0.02) fewer cells (26%) expressing the pan T cell phenotype in comparison to LPL (38%) and PPL (44%). Similarly, significantly (P less than 0.01 to 0.001) lower numbers of B cells were observed among IEL (10%) compared to LPL (28%) and PPL (33%). While approximately equal numbers of B7A1+ "null" cells (10%) and DH59B+ "Ia+ monocytes/granulocytes" (16.5%) were observed among the three intestinal cell populations, IEL contained significantly (P less than 0.1 to 0.05) lower numbers (19%) of T helper (Th) cells in comparison to LPL (44%) and PPL (38%). In contrast, lymphocytes with the T cytotoxic/suppressor (Tc/s) phenotype were significantly lower (P less than 0.01 to 0.001) among LPL (14.5%) compared to IEL (25%) and PPL (23%). While the numbers of cells expressing class I major histocompatibility complex (MHC) surface antigens (H58A+) were approximately equal among LPL (79%) and PPL (87%), a significant difference (P less than 0.02) was observed between IEL (71%) and PPL. Similarly, while approximately equal numbers of cells expressing the MHC class II surface phenotype were observed among LPL (42%) and PPL (46%), IEL contained significantly (P less than 0.01) fewer (31%) MHC class II cells in comparison to PPL. Enrichment for T cells by plastic adherence and Sephadex G 10/nylon wool fractionation revealed a significant (P less than 0.01) and proportional increase in T lymphocyte subsets expressing pan T, Th and Tc/s phenotypes among the three cell populations. Similarly, enrichment for B cells by the same techniques showed a significant (P less than 0.01) and proportional increase in cells expressing the panB cell phenotype among LPL and PPL. Marked differences in cell size distribution and cell surface density were observed when the three intestinal leukocyte populations were compared by LFC using monoclonal antibodies directed at various cell surface markers. Furthermore, considerable quantitative variations of each cell surface marker were observed among the individual animals tested. The results of this study indicate that bovine IEL, which contain a high percentage of cells (greater than 30%) with no known phenotype are significantly different from LPL and PPL which are phenotypically similar cell populations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2603382 TI - Significance of Freund's adjuvant/antigen injection granuloma in the maintenance of serum antibody response. AB - An experimental system involving injections of ovalbumin (OVA) and ferritin (FER) in Freund's incomplete adjuvant (FIA) into the right and left flank skin folds of sheep was used to study the influence of the FIA/antigen depot and the draining lymph node in maintaining an antibody response. Excision of the injection granuloma and draining lymph node from one side 2-3 months after injections resulted in a profound decrease in serum antibody titres. This response was observed in all eight sheep in the experimental group. In five of eight animals in another experiment, excision of the injection sites had no appreciable effect on antigen-specific antibody titres when compared with antibody specific for antigen on the intact side of the sheep. In the remaining three animals, excision of the injection site did cause some fall in titre. Radiotracer studies revealed that about one-third of the original [125I]OVA/FIA injected was present in the granuloma 20 weeks after injection. Lymphatic cannulation approaches were used to study the responsiveness of the lymph node draining an FIA/antigen granuloma established 12 weeks earlier and showed that increments of 1-2 mg OVA in saline administered adjacent to the granuloma at 6-7 day intervals gave rise to strong anti-OVA containing cell (AOCC) responses in lymph. There were 2-6-fold increases in serum antibody titre in response to 3-5 doses of OVA or FER (1-2 mg) in saline injected adjacent to the FIA/antigen injection site (which had been administered 14-16 weeks previously). It is concluded that the release rate of antigen from a FIA/antigen depot is insufficient to sustain maximal antibody levels in blood serum. PMID- 2603383 TI - Lymphocyte reactivity to mitogens and natural killer cell activity in crossbred swine during the reproductive cycle. AB - The effect of pregnancy and lactation on the cell-mediated immune response of first litter gilts was assessed using the response of circulating lymphocytes to in vitro mitogen stimulation and the cytotoxic activity of the circulating natural killer (NK) cells. Groups of gilts were sampled during the first, second and third trimester of gestation, weekly during lactation, at weaning and estrus following weaning of the piglets. No significant differences were found in the response of the cells from any of the groups to phytohemagglutinin A or concanavalin A stimulation. The natural killer cell activity, measured as cytotoxicity, decreased during gestation reaching a low point during the second and third week of lactation. PMID- 2603384 TI - Effect of immunotherapy on the serum concentrations of allergen-specific IgG antibodies in dog sera. AB - An ELISA assay which uses horseradish peroxidase conjugated anti-canine IgG and polystyrene microtiter wells for detection of allergen-specific IgG in the serum of dogs is described. Individual allergen blanks were used to account for the variable nonspecific binding among various allergens, and the results observed in milliunits of absorbance were normalized using four reference sera. The coefficients of variation for the intraassay and interassay variability ranged from 1.34 to 12.50% and 4.62 to 9.77%, respectively. The relationship between ELISA results and serum concentrations of allergen-specific IgG was quantified. IgG antibodies with specificity for various allergens were found in the majority of non-atopic individuals and in all atopic subjects. Specific immunotherapy resulted in a rise in the serum concentration of allergen-specific IgG. PMID- 2603385 TI - Serum IgG and IgM antibody response in cattle to antigens of Pasteurella haemolytica. AB - The serum IgG and IgM antibody responses of 48 cattle vaccinated with live Pasteurella haemolytica (LIVE), formalin-killed P. haemolytica in Freund's incomplete adjuvant (FIA), or formalin-killed P. haemolytica in aluminum hydroxide adjuvant (ALH) to a variety of P. haemolytica antigens were evaluated. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the sequential and day 21 IgG and IgM antibody responses to whole P. haemolytica (WB), a capsular carbohydrate-protein subunit (CPS) extracted from the organism, P. haemolytica capsular carbohydrate (CC), and P. haemolytica leukotoxin (LT). LIVE and FIA vaccinates developed generally higher IgG and IgM responses to all antigens compared to ALH vaccinates. LIVE vaccinates developed IgG responses to LT which were significantly higher (P less than 0.05) than all other vaccinates. In contrast, FIA vaccinates developed significantly higher IgG responses to CPS than all other vaccinates. On the basis of the ELISA results, similar or cross reacting antigenic sites were present in preparations containing surface antigens (WB, CPS and CC), but not LT. Disease resistance, as determined by experimental lesions induced in the 48 calves by transthoracic challenge with P. haemolytica, was significantly greater in the LIVE and FIA vaccinates compared with ALH vaccinates. No significant difference in resistance was detected between LIVE and FIA vaccinates. Lesions in ALH vaccinates were not significantly different than those in phosphate-buffered saline (PBS) controls. Increased IgG responses to all antigens were significantly associated with resistance to experimental disease; however, IgG responses to CPS were most highly correlated with resistance. The only IgM response which was significantly correlated with resistance was the response to CPS. These studies indicate that serum IgG antibody responses to various surface antigens of P. haemolytica, as well as LT, can enhance resistance to experimental pneumonic pasteurellosis. Serum IgM responses, however, do not appear to play a major role in resistance to experimental disease. PMID- 2603386 TI - Peanut agglutinin (PNA): binding and stimulation of bovine intestinal and peripheral blood leukocytes. AB - The use of peanut agglutinin (PNA) as a reliable marker for bovine T lymphocytes as well as its in vitro lymphoblastogenic capacity were investigated and compared to those of concanavalin-A (ConA). The binding ability of fluorescein isothiocyanate conjugated PNA (FITC-PNA) and FITC-ConA to bovine leukocytes isolated from peripheral blood (PBL) as well as from the intraepithelium (IEL), lamina propria (LPL) and Peyer's patches (PPL) of the small intestinal mucosa of five normal adult cows (n = 5) was analyzed using laser flow cytometry (LFC) and fluorescence microscopy. Monoclonal antibodies (mAb) specific for bovine T cells (B26A), B cells (PIg45A), "null" cells (B7A1) and monocytes/granulocytes (DH59B) were employed to determine the phenotype of the cell lineage(s) expressing PNA surface receptor(s). There were no significant variations (P greater than 0.1) in the proportion of PNA-binding cells in PBL (76%), PPL (77%), IEL (79%) and LPL (81%) even though there were significant differences between the percentages of B26A+ T cells in IEL (26%) and LPL (38%) (P less than 0.001) and in PPL (44%) and PBL (57%) (P less than 0.01). These studies clearly indicate that cells other than T cells bind PNA. Although the proportions of PNA-binding cells in enriched PP-B cells (30%) and enriched PP-plastic adherent cells (44%) were significantly lower (P less than 0.001) than those in enriched PP-T cells (95%), the results indicated that a reasonable number of non-T cells can specifically bind FITC-PNA. Additional support was obtained by similar results observed with the equivalent cell subsets from PBL. Using in vitro lymphoblastogenesis, the PNA stimulating capacity significantly varied between the various cell populations (P less than 0.001 between IEL and PBL; and P less than 0.02 between PPL and PBL). In addition, marked differences were observed between the binding ability and stimulating capacity of PNA on each leukocyte population (P less than 0.01 in PBL to P less than 0.001 in IEL). Concanavalin A which bound to approximately 100% of each cell population, revealed significant variation in its mitogenic activity between IEL and PBL (P less than 0.001) but not between LPL and PPL (P greater than 0.1). The finding that PNA can bind to bovine T cells as well as to some B cells, monocytes/macrophages and possibly some granulocytes and "null" cells disputes its reliability as a specific bovine T cell marker. Furthermore, the binding abilities of PNA and ConA to bovine leukocytes are not necessarily correlated to their in vitro mitogenic capacities. PMID- 2603387 TI - Activated porcine alveolar macrophages: are biological response modifiers the answer? AB - We report that 75% of conventionally housed 3- to 4-week-old swine already have detectable activated alveolar macrophages as measured by cytotoxicity of tumor cells. These macrophages can not be further activated by the biological response modifier N-acetylmuramyl-L-alanyl-Disoglutamine-2H2O (MDP). These macrophages lose cytotoxic activity when cultured for 24 h and this loss of activity can not be reversed by MDP. We suggest that MDP biological response modifier therapy of swine alveolar macrophages may not be a useful technique in preventing respiratory disease in swine. PMID- 2603388 TI - The spike generating mechanism of cat retinal ganglion cells. AB - The spike generating mechanism (SGM) of sustained and transient-type ganglion cells has been investigated from intracellular recordings in the cat retina. The relationship between the generator potential and the impulse pattern, which are respectively the input and the output of the SGM, has been studied after separating one component from the other. Comparison of averaged generator potentials and the corresponding PSTHs showed that the spike generator is highly sensitive to changes of the generator potential. It proved to be relatively indifferent to the prevailing average levels of depolarization. During sustained parts of the responses the SGM exhibits a stochastic nature. At higher light flicker frequencies, during spike bursts, on the other hand spike generation is very regular and phase locked to the stimulus. The averaged generator potentials were also used to develop and test a set of minimal, computer simulated models of the spike generator. A slow threshold adaptation (time constant about 50 msec) is absolutely necessary in addition to the faster refractory recovery in order to produce spike patterns similar to those measured during the corresponding response periods. The developed model accounts completely for the observed characteristics of ganglion cell spike generation under a wide variety of light stimulus regimes and both for the sustained and for the transient type of ganglion cell. PMID- 2603389 TI - Spectral properties of porphyropsin from an invertebrate. AB - Winter crayfish (Procambarus clarkii) contain both retinal and 3-dehydroretinal, as first described by Suzuki, Makino-Tasaka and Eguchi (1984). Using the detergent L-1695 we have extracted visual pigments from the rhabdoms of crayfish and have characterized spectrally both rhodopsin (P1) and porphyropsin (P2). Both P1 and P2 are converted by light to relatively stable meta-pigments (M1 and M2). We here show a method for estimating the absorbance spectra of all four pigment species. The spectra of P533(1) and M510(1) agree with previous microspectrophotometric measurements on isolated rhabdoms. P567(2) and M537(2) represent the first 3-dehydroretinal-based visual pigment system to be characterized from an arthropod. PMID- 2603390 TI - Computer methods for sampling, reconstruction, display and analysis of retinal whole mounts. AB - We are quantifying the distribution of photoreceptors and ganglion cells in human retina with the goal of establishing a reliable anatomical database which may be compared to information about visual function. We required a representation of retinal cell distributions which facilitated collection, analysis, and display of morphometric data from the entire retina of a large number of eyes. We report computer methods to (1) reconstruct the original retinal sphere from a three piece whole mount preparation; (2) sample the retina in a manner which allowed description of approximately radially symmetrical cell distributions and avoided both undersampling (which produces interpolation artifacts) and oversampling (which wastes time); (3) interpolate between data points in order to produce plots of cell density along arbitrary meridians and maps of average cell density from several eyes; (4) specify locations on the retinal surface using a spherical coordinate system with its primary axis through the fovea; and (5) produce color coded maps of cell distributions in a standard perimetric projection. PMID- 2603391 TI - APB increases apparent coupling between horizontal cells in mudpuppy retina. AB - 2-Amino-4-phosphonobutyrate (APB), an agonist at a unique type of glutamate receptor on depolarizing bipolar cells, caused an apparent increase in coupling between horizontal cells as evidenced by a decrease in amplitude of responses to illumination of the receptive field center and an increase in responses to illumination of the peripheral part of the receptive field. APB also caused a hyperpolarization of horizontal cells in darkness and increased the amplitude of responses to full-field illumination, which cannot be explained by an increase in electrical coupling between horizontal cells. Possible mechanisms for these actions are discussed. PMID- 2603392 TI - Influence of mechanical disturbance on oculomotor behavior. AB - Using a binocular search coil technique, we measured oculomotor behavior during gentle pressing with a finger on the outer canthus of one eye. With a steadily pressed viewing eye, and the fellow eye occluded, the occluded eye deviates while the pressed eye does not. If the eye is rapidly pressed and released, the compensation of rotational force in the pressed eye becomes incomplete, so that both eyes move. At high frequencies of press (greater than 1 Hz) the pressed eye is deviated and the contralateral eye no longer moves. In darkness the pressed eye always rotates but the contralateral eye never does, demonstrating that any inflow from proprioceptors sensing rotation of the pressed eye does not affect oculomotor posture as measured in the fellow eye. With binocular viewing the results are more variable. On some trials neither eye moves, while on others both move. The results can be interpreted as a Hering's law controlled attempting to reconcile disparate inputs from the two eyes. The results confirm and extend, with objective measures, earlier conclusions from subjective experiments. PMID- 2603393 TI - Is there a constancy for velocity? AB - Human observers are unable to use disparity information to transform the angular velocity signal into a precise object-based code. The Weber fraction for discriminating changes in objective velocity (cm/sec) is about twice the Weber fraction for discriminating changes in angular velocity (deg/sec), and is substantially higher than predicted from a combination of the errors in judging disparity and angular velocity. By comparison, judgments of the distance traversed by the moving target show excellent size constancy. The discrimination of changes in objective size (cm) is as precise as the discrimination of changes in angular size (deg). The angular velocity signal is useful without transformation into an object-centered signal; it guides eye and body movements, and is the basis of motion parallax judgments. The need to retain this angular signal may explain why there is no efficient mechanism for velocity constancy. PMID- 2603394 TI - Variable contributions of rods and cones to saccadic eye-movement latency in a non-foveating task. AB - Latencies were measured for anti saccades away from a small lit cue that steps +/ 10 deg in complete darkness. Cue luminance and wavelength were varied. Additional measurements were made during dark-adaptation or on backgrounds or at different retinal eccentricities. Luminance matched cues and Palmer's equivalent luminance transformation were also used. Latencies for pure rod and pure cone inputs obey Pieron's law in much the same manner as foveating saccades, except that latencies are somewhat longer. However, as judged by saccadic latency, interaction between rods and cones is quite variable in the anti task. The rod cone transition either occurs at cue luminances well above the cone threshold and is from pure rod input to primarily cone, or occurs at the cone threshold and is from rods to rods-plus-cones. Direction errors, or reflex foveating saccades, are particularly increased for mesopic cues. The variable behaviour of subjects at the anti task is discussed in relation to temporal multiplexing of rod and cone signals from dark-adapted retinal ganglion cells, the delaying nature of the task, and attentional mechanisms. PMID- 2603395 TI - Size, flux and luminance effects in the apparent motion correspondence process. AB - The effects of the relative size, luminance, and total luminous flux of apparent motion visual stimulus disk elements are studied, using a competitive paradigm. These dimensions can only be studied in pairs and we find that all three pairs have significant correspondence process effects. A comparison of the magnitudes of the effects, however, suggests that size and flux are the dimensions relevant to apparent motion processing, while luminance may not contribute to the correspondence process. Pitting distance against these dimensions in apparent motion tasks, we were able to find effective equivalence scales among them. Finally, interactions were found between the processing of some of these dimensions. The most pronounced interaction effect is that the addition of the size dimension increases the noise in the processing of distance, while size processing is not affected by the addition of the distance cue. PMID- 2603396 TI - Is edge information for stereoacuity spatially channeled? AB - Models of stereopsis generally assume that binocular correspondence is achieved through alignment of luminance edges in the two eyes. Yet the stimulus properties which constitute edge information for stereopsis have not been defined. Three experiments explored the nature of these stimulus properties. The first two experiments tested whether local luminance gradient and the relative phase of spatial components supply information about the position of edges which influences stereosensitivity. In Expt 1, stereothresholds were reduced with increased spatial frequency or contrast of sinusoidal luminance gratings, but no simple relationship between target luminance gradient and stereosensitivity was found. In Expt 2, stereothresholds were equivalent for targets having identical spatial frequency components, but differing in maximum luminance gradient and the relative spatial phase of their components. In addition, stereothresholds were lower for the target having the higher contrast in pairs of unequal-contrast targets having equal maximum luminance gradients. These results suggest that the properties of luminance gradient and relative spatial phase do not influence stereosensitivity independently of spatial frequency and contrast. Experiment 3 directly tested whether stereosensitivity depends on edge information whose disparity is detected independently at different spatial scales. Stereothresholds for IF + 5F compound targets were found to be equivalent to thresholds obtained separately with the more sensitive of the two components. Taken together with a compressive nonlinearity in the relationship between contrast and stereothreshold obtained by others (Halpern and Blake, 1989; Legge and Gu, 1989) and replicated in Expt 1, the results of Expt 3 indicate that, whatever the exact nature of the luminance discontinuity information utilized in disparity detection, it is processed independently at different spatial scales. PMID- 2603397 TI - McCollough aftereffects in strabismus and amblyopia. AB - In strabismic people, the functioning of the deviating eye is impaired. This impairment is binocular in origin since it depends on stimulation of the straight eye; sensitivity and acuity of the deviating eye are usually better when the straight eye is patched than when both eyes are viewing. We investigated interactions between the eyes in strabismic people by using the McCollough color aftereffect as an exploratory procedure. Both normal and strabismic people adapted to black and colored bars and then examined black and white test bars. They reported colors in the achromatic test bars that were complementary to the adapting colors; this is the McCollough aftereffect. Both a monocular McCollough effect and a binocular McCollough effect were induced in people having normal vision. Strabismic people did not show a binocular McCollough effect. Aftereffect strengths were the same in each eye of normal people but were stronger in the impaired eye of strabismic people. A speculation is offered as to why the "non seeing" eye of strabismic people "sees" the aftereffect better. PMID- 2603398 TI - Occlusion and the solution to the aperture problem for motion. AB - The "aperture problem" indicates that a local reading of the velocity of an oriented contour is inherently ambiguous, insufficient by itself to recover the velocity of image points. In Wallach's "barber pole" display consisting of moving diagonal lines within an elongated rectangular aperture, it has been suggested that the unambiguous motion of edge-terminators along the longer edges of the aperture propagates towards the motion-ambiguous center part of drifting stripes. This results in the perception of a surface moving in the direction of the longer axis of the aperture. By manipulating the stereoscopic disparity of a striped pattern relative to the aperture plane, we found that the disambiguating effects of terminators could be abolished if the striped pattern was in uncrossed disparity relative to the aperture plane. Also, the motion in 3 separate horizontally oriented, and vertically aligned apertures which would otherwise be seen as moving horizontally, was seen as "linked" together and moving vertically. This occurred only when the horizontally oriented segments separating these apertures were stereoscopically coded so that they appeared as occluders in front. These findings suggest that accidental or "extrinsic" terminators created by occluding edges are treated differently from real or "intrinsic" terminators, and that the real-world constraint of occlusion is thus implemented in the ambiguity-solving processes for motion. PMID- 2603399 TI - Measurement of spatial contrast sensitivity with the swept contrast VEP. AB - Contrast response functions (CRFs) for the VEP were obtained with a Discrete Fourier Transform (DFT) technique employing swept contrast gratings. VEP CRFs in infants were found to have a form similar to those observed in adults, being linear functions of log contrast over a range of near-threshold contrasts. CRFs with low and high contrast lobes were present in infants, as they are in adults. Contrast thresholds were estimated by extrapolation of the CRF to zero microvolts. The effects of additive EEG noise and of the DFT data window on the shape of the measured CRF are considered. For large signals, the measured CRF is nearly independent of the additive noise, but at small signal values additive noise introduces a small bias towards larger amplitudes. The VEP signal-plus noise distribution was modeled as a family of Rice distributions in order to evaluate the effects of bias on the estimates of threshold. The amount of bias depends inversely upon the slope of the CRF. The amount of bias introduced by a smoothing window also depends upon slope of the CRF as well as the sweep rate. The combined effects of additive noise and window bias were such that the total bias was nearly independent of CRF slope. Sweep VEP contrast thresholds were shown empirically to be unaffected by changes in the range of contrast swept. PMID- 2603400 TI - [The achievements and trends in research on the path toward a general theory of physical therapy]. PMID- 2603401 TI - [The effect of a sauna on the reactivity of the circulatory indices in an isometric load test]. AB - The response of cardiovascular parameters to measured hand grip exercise has been studied in healthy men frequenters of sauna. The results demonstrate leveling of initially registered individual deviations in reactivity of vasomotor center and related variants in the response of cardiac regulation mechanisms. PMID- 2603402 TI - [A comparative assessment of changes in cardiovascular function under the influence of sodium chloride baths and underwater douche-massage for optimizing programs for the sanatorium treatment of patients with ischemic heart disease]. PMID- 2603403 TI - [The use of static-regimen training exercises with patients having had a myocardial infarct in combined sanatorium physical rehabilitation]. PMID- 2603404 TI - [The influence of music on the effectiveness of therapeutic physical exercises in patients with cardiovascular and respiratory pathologies]. AB - Medical and pedagogical observation performed during hours of therapeutic exercise in groups of cardiovascular and respiratory diseases patients proved a beneficial effect of music accompaniment. This was most efficient when started from the very onset of the exercise course for the former group of patients and from the second week of the exercise course for the latter patients. It is stated that music should be used differentially at different stages of hospital conditioning. PMID- 2603405 TI - [Sanatorium treatment combined with acupuncture in patients with the initial manifestations of insufficient blood supply of the brain]. PMID- 2603407 TI - [The differential use of cavitary pelomagnetotherapy in various forms of chronic proctosigmoiditis]. PMID- 2603406 TI - [Mud treatment of patients with rheumatoid arthritis with an immunologic deficiency]. AB - The response to pelotherapy has been assessed clinically and immunologically basing on T-lymphocyte count. Altogether 124 rheumatoid arthritis (RA) patients were examined. In patients with low baseline levels of T-lymphocytes the effect of pelotherapy appeared inferior to that in patients with normal T-lymphocyte counts. It was suggested that T-cell immunosuppressed RA patients should receive combined therapy with mud applications and anabolic stimulator potassium orotate. PMID- 2603408 TI - [Endourethral phonophoresis of lipase in the combined treatment of strictures of the urethra]. AB - Poor results of surgical treatment of posttraumatic and inflammatory urinary strictures have urged the authors to the search and introduction into clinical practice of a multimodality conservative treatment combining conventional urethroplasty, transurethral manipulations with following local endourethral lydase phonophoresis. The treatment has been conducted in 104 men aged 15-78. The final analysis of the trial demonstrated the advantages of the proposed method as to the duration of the treatment and prevention of the strictures recurrences. Detailed consideration is given to the indications, technique, long-term response. The objective approach has been achieved by tracing dynamic changes in the low urinary tract. PMID- 2603409 TI - [The action of massage on lymph formation and transport]. AB - Acute tests on anesthetized dogs revealed stimulation of local lymphization and lymph transport following manual massage of tissues. Lymph levels of protein and lymphocytes rose. PMID- 2603410 TI - [The use of sinusoidal modulated currents by segmental methods of action for restoring work capacity in athletes]. PMID- 2603411 TI - [Biophysical bases for determining the permissible parameters of laser exposure in therapeutic practice]. PMID- 2603412 TI - [The late results of helioaerotherapy in the combined treatment of patients with chronic bronchitis]. PMID- 2603413 TI - [Characteristics of the effect of medical gymnastics on the cerebral hemodynamics in patients with cervical osteochondrosis]. PMID- 2603414 TI - [The clinical efficacy of electroacupuncture in treating patients with infectious allergic bronchial asthma]. PMID- 2603415 TI - [The use of decimeter waves in the combined treatment of patients with myasthenia]. PMID- 2603416 TI - [Therapeutic physical exercise as a method of maintenance therapy under home conditions]. PMID- 2603417 TI - Biweekly intracavernous administration of papaverine for erectile dysfunction. AB - To determine the efficacy of the intracavernous administration of papaverine hydrochloride every 2 weeks to treat male impotence, we recruited 50 patients from a sexual dysfunction clinic. Of these, 8 did not complete the course of papaverine therapy. A total of 8 had complications, including priapism in 3 and ecchymoses or urethral bleeding in 5. In 30 patients who had substantial vasculogenic disease, there was a notable improvement in the penile blood pressure after papaverine treatment, although only 9 reported successful sexual intercourse. The penile blood pressure in the remaining 12 patients without substantial vascular disease increased modestly after therapy, and 5 persons reported satisfactory sexual activity. We conclude that administering papaverine intracavernosally every 2 weeks improves sexual potency in a subset of sexually impotent patients. Those with severe vasculogenic disease and a penile-brachial pressure index of less than 0.65 are not good candidates for this regimen. PMID- 2603418 TI - Blastocystis hominis--a potential intestinal pathogen. AB - The parasite Blastocystis hominis has been found in 10% to 18% of stool specimens submitted to microbiology laboratories. Controversy exists as to whether this organism can cause illness in humans. We have reviewed the records of 65 symptomatic patients with B hominis in their stool. We conclude that B hominis is a potential pathogen that may or may not require drug therapy depending on the overall clinical circumstances, the severity of symptoms, and the presence of other pathogenic organisms. PMID- 2603420 TI - Cirrhosis, alcohol, and the heart. PMID- 2603419 TI - Epiglottitis--an increasing problem for adults. AB - In a 2-year period, 9 adults were admitted to hospital with acute epiglottitis confirmed by direct laryngoscopy or lateral neck radiograph, or both. The mean age was 53 +/- 14 years, with acute epiglottitis occurring in 89% during the months of September to March. Intubation was required in 4 patients. The duration of symptoms was 7.8 +/- 2.4 hours for intubated patients versus 18.8 +/- 8.9 hours for those not intubated. For 6 patients an incorrect diagnosis was made on their first presentation. All 8 patients having laryngoscopy had typical findings, and none had respiratory obstruction precipitated by the procedure. In 5 patients blood cultures were positive, 4 for Hemophilus influenzae type b, and 1 for Streptococcus pneumoniae. In 2 patients the H influenzae was ampicillin resistant. All patients recovered after receiving parenteral steroid therapy and appropriate antibiotics. PMID- 2603421 TI - Professional values and organized medicine. PMID- 2603422 TI - Aortic valvulitis in a patient with Wegener's granulomatosis. PMID- 2603423 TI - Intestinal pseudo-obstruction related to using verapamil. PMID- 2603424 TI - Kingella kingae endocarditis in a patient with the acquired immunodeficiency syndrome. PMID- 2603425 TI - The peer review process. PMID- 2603426 TI - Are they really serious? PMID- 2603427 TI - Genes and dreams. PMID- 2603428 TI - Superior mediastinal mass with hypertension. Pseudocoarctation of the aorta. PMID- 2603429 TI - Magnetic resonance imaging versus X-ray computed tomography--which is the appropriate first imaging examination? PMID- 2603430 TI - Transitions. PMID- 2603431 TI - The 'art' of medicine. PMID- 2603432 TI - The relation of the holocaust to bioethics. PMID- 2603433 TI - Something especially good is happening. PMID- 2603434 TI - Cardio-pulmonary resuscitation in a community hospital. PMID- 2603435 TI - A doctor in the house. Interview by Kathryn Derene. PMID- 2603436 TI - Publicity, policy and trends in cigarette smoking: Wisconsin 1950-1988. PMID- 2603437 TI - Euthanasia and the British Medical Association. PMID- 2603438 TI - Continuous verapamil infusion. PMID- 2603439 TI - Neuromuscular blocking agents in burn patients. PMID- 2603440 TI - Pediatric bowel evacuation with a polyethylene glycol and iso-osmolar electrolyte solution. PMID- 2603441 TI - Formulary conversion of cefoxitin usage to cefotetan: experience at a large teaching hospital. AB - The pharmacy and therapeutics committee at Hartford Hospital recommended replacement of cefoxitin with cefotetan, based on data reported in the literature regarding antimicrobial activity, pharmacokinetic profile, and adverse reactions. Once the recommendation was approved by the medical staff, an intense educational program was instituted, and all orders for cefoxitin were converted to cefotetan with appropriate dosage modifications. A total of 960 patients were treated in the first year; no major patterns of ineffectual therapy or adverse events associated with cefotetan usage have emerged. The mean cost of cefotetan therapy was $180.59, which is $130.26 less per patient than a comparable regimen of cefoxitin (mean cost of therapy $310.85). Based on the data analysis of cefotetan usage for a 12-month period, the actual annual savings due to therapeutic substitution of cefotetan for cefoxitin was $124.961. To further evaluate the clinical efficacy, safety, and savings of this therapeutic interchange, two separate retrospective reviews of patient medical records were performed. The first audit has been previously published in its entirety. In the subsequent audit, 284 additional patient medical charts have been reviewed. These patients received either cefotetan therapy or concomitant therapy of an aminoglycoside combined with either clindamycin or mezlocillin. Clinical outcomes were classified as an empiric cure or improvement for 99.4, 98.5, and 92.9 percent of patients, respectively. In this audit, elevated prothrombin time/partial thromboplastin time values and bleeding episodes were noted infrequently, as were other adverse reactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2603442 TI - Pharmacotherapy. Part II. Administering the certification process. PMID- 2603443 TI - Successful prevention of an anaphylactoid reaction to high-dose methotrexate. PMID- 2603444 TI - Possible sulfite sensitivity with gentamicin infusion. PMID- 2603445 TI - Vitamin B12-induced folliculitis. PMID- 2603446 TI - Effects of carbamazepine on serum calcium in schizophrenia. PMID- 2603447 TI - Buspirone: potentials for abuse? PMID- 2603448 TI - Stability of caffeine injections stored in plastic and glass syringes. PMID- 2603449 TI - Comment: oral clonidine in nicotine withdrawal. PMID- 2603450 TI - Comment: foreign drug identification. PMID- 2603451 TI - Estimation of creatinine clearance in patients with Cushing's syndrome. AB - The predictive value of the Cockcroft-Gault equation in patients with Cushing's syndrome was evaluated in 23 patients. Patients were subdivided based on total body weight into two groups, obese and nonobese. Estimated creatinine clearance (EClcr) values were obtained by the Cockcroft-Gault method using ideal body weight (IBW) and total body weight (TBW). These values were then compared with a 24-hour measured creatinine clearance (MClcr). EClcr values based on TBW consistently overestimated measured values in all patients (p less than 0.05). In obese patients with Cushing's syndrome IBW predictions were not statistically different. However, linear regression analysis revealed a poor correlation (r = 0.32). Daily creatinine production rates (Ucr) were calculated and contrasted with an appropriate historical control for obese and nonobese subjects. Nonobese patients revealed a marked reduction in total Ucr compared with normal-weight controls (p less than 0.05). Obese patients also showed a reduction in Ucr when compared with a normal obese control population (p less than 0.05). Difficulty in predicting creatinine clearance in patients with Cushing's syndrome appears to be related to alterations in Ucr. These data suggest that the pathophysiologic changes that accompany Cushing's syndrome are sufficient to alter Ucr and may limit the usefulness of existing methods to predict creatinine clearance and renal function in these patients. PMID- 2603452 TI - Estrogen replacement therapy: a pilot survey of primary care physicians in West Virginia. AB - Controversy surrounds the optimal use of estrogen replacement therapy (ERT) for the management of vasomotor instability and other perimenopausal symptoms. This fact and the obvious lack of published literature regarding physician prescribing behavior led the investigators to explore these issues with primary care physicians in West Virginia. Data were collected using a mailed, self administered questionnaire. Issues addressed included reasons for using/not using ERT, patient symptoms, type of therapy prescribed, treatment duration, and symptom resolution or rebound. Approximately 25 percent of the 420 physicians contacted responded to the questionnaire. The overwhelming majority prescribes ERT for their patients. Most physicians prescribe an estrogen/progesterone combination for some or all patients, depending on the clinical situation. Conjugated estrogens in physiologic doses and synthetic progestins are most frequently prescribed and administered on a cyclic basis. Most women prescribed ERT experienced symptom resolution. Treatment outcome was not correlated with treatment duration. PMID- 2603453 TI - Cost analysis of two clindamycin dosing regimens. AB - A clinical trial of clindamycin 900 mg q8h admixed with gentamicin 1.5 mg/kg (eight-hourly group) versus clindamycin 600 mg q6h with gentamicin 1.5 mg/kg given separately (six-hourly group) was analyzed for relative cost containment. Acquisition costs were significantly higher for the six-hourly group for intravenous supplies ($181.5 +/- 47.8) when compared with the eight-hourly group ($67.6 +/- 21.6) (p less than 0.05). Nursing administration costs were greater for the six-hourly group ($28.6 +/- 7.5) compared with ($10.7 +/- 3.4) for the eight-hourly group (p less than 0.05). Also, significantly higher cost (p less than 0.05) was noted for pharmacist and technician manufacturing cost for the six hourly group ($15.4 +/- 4.0) compared with the eight-hourly group ($13.3 +/- 4.3). Incorporating all appropriate costs, the mean total drug therapy costs were significantly greater (p less than 0.05) for clindamycin 600 mg q6h ($527.4 +/- 143.0) compared with clindamycin 900 mg q8h ($433.3 +/- 99.2). The dosing of clindamycin 900 mg q8h admixed with gentamicin 1.5 mg/kg is a more cost-effective method of drug delivery with similar efficacy and safety when compared with clindamycin 600 mg q6h with gentamicin given separately. PMID- 2603454 TI - Streptokinase-induced anaphylaxis. AB - Streptokinase is a thrombolytic agent used most commonly for the dissolution of thrombi obstructing coronary arteries during acute myocardial infarction (MI). Anaphylactic reactions induced by streptokinase occur rarely. We report the case of a patient with acute MI who developed anaphylaxis shortly after the initiation of an intravenous infusion of streptokinase. The patient became profoundly hypotensive and developed an erythematous rash that spread rapidly to cover most of his body. He required mechanical ventilation and the administration of epinephrine for blood pressure support, which succeeded after dopamine and norepinephrine had failed. Streptokinase-induced anaphylaxis is thought to be mediated by immunoglobulin E (IgE), and patients who develop this adverse reaction have been shown to have higher serum concentrations of IgE to streptokinase than those who do not. Epinephrine is the agent of choice for the management of hypotension associated with anaphylaxis. Little evidence exists to support the routine pretreatment of patients who are to receive streptokinase with corticosteroids and/or antihistamines. Streptokinase skin testing may be a useful and accurate means of identifying patients at risk for streptokinase induced anaphylaxis. Further investigation is required to determine the appropriateness of skin testing in streptokinase therapy. PMID- 2603455 TI - Verapamil-associated Stevens-Johnson syndrome. AB - Stevens-Johnson syndrome (SJS) is a complication infrequently associated with the use of calcium-channel blocking agents. A 59-year-old woman developed symptoms typical of SJS approximately ten days following the initiation of sustained release verapamil for hypertension management. Symptoms consisted of a generalized red macular rash associated with swelling of the face, tongue, lips, and mouth as well as a fever of 40 degrees C. Resolution of symptoms began approximately four days after verapamil discontinuation. Rechallenge with verapamil was not performed. Although SJS appears to be a rare adverse effect of this drug, the potential complications warrant the inclusion of SJS in the differential diagnosis of patients presenting with malaise, fever, rash, and a history of verapamil ingestion. PMID- 2603457 TI - [The relationship of analytic to biological variance--consequences for diagnosis and for the choice of laboratory tests]. AB - The paper deals with the formal dependence of diagnostic efficiency of clinical laboratory methods from analytic error. The parameters of frequency distribution and the estimation of variance of the analytical error are taken into account. This dependence is constructed basing on an universal model for solving classification tasks using error-contaminated data. The diagnostic efficiency is calculated as a function of the variance of analytical error. A comparison of calculated efficiencies with data gained in a special experiment showed a good agreement. PMID- 2603456 TI - Panic attacks and major depression after discontinuation of long-term diazepam abuse. AB - A case is described of a patient with a history of several years of diazepam abuse (in the last 24 months at dosages of 120 mg/d). A tapering schedule was carried out during a 12-day stay in the hospital in which the diazepam dosage was reduced by a fixed quantity every day, corresponding to about ten percent of the initial dosage. Five days after discharge from the hospital the patient experienced panic attacks, for the first time, which continued until 13 days after discharge. By the 40th day, the patient was experiencing a major depressive episode, which improved after administration of clomipramine therapy. We suggest that a relatively quick withdrawal schedule (ten percent per day) is probably inadequate in preventing withdrawal reactions to long-acting benzodiazepines taken in high doses for an extended period of time. PMID- 2603458 TI - [Biochemical changes in skeletal muscles after chronic indirect stimulation]. AB - The skeletal muscle has the capacity to respond adaptively to increased use. This observation could open up the feasibility of constructing pumping chambers to support or even replace cardiac work. We investigated the changes in enzyme activity due to chronic stimulation in an animal skeletal muscle. In 5 adult sheep the psoas muscle of one side was electrically stimulated through the muscle nerves, with an implantable stimulation unit for 5 weeks. The activity of the hexokinase (E.C.2.7.1.1.), lactate dehydrogenase (E.C.1.1.1.27), malate dehydrogenase (E.C.1.1.1.37), creatine kinase (E.C.2.7.3.2.) choline acetyltransferase and the contents of adenosine triphosphate and adenosine diphosphate were determined in bioptic specimen. The use of only 15 Hertz as a stimulation frequency led to a transformation of an originally fast-twitch muscle into a slow-twitch muscle with reduced susceptibility to fatigue. These results indicate a potential role of the skeletal muscle as an ideal myocardial substitute with the ability to perform hemodynamic work. PMID- 2603459 TI - Changes of activities of some transferases, alkaline phosphatase and cholinesterase in the blood of women using oral contraceptives and in vitro influence of these agents on tissular enzyme levels in rat liver. AB - Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, and alkaline phosphatase activities in the blood serum of women taking the oral contraceptive preparation Microgynon through extended periods were raised; the activity of cholinesterase was simultaneously reduced. In rats liver homogenates ethynylestradiol, one of the active components of Microgynon, acted as an inducer of gamma-glutamyltransferase and alkaline phosphatase while leaving aspartate aminotransferase and alanine aminotransferase unaffected, but reduced the level of cholinesterase. Norgestrel, the other active component of the preparation, suppressed the biosynthesis of gamma-glutamyltransferase and alkaline phosphatase while leaving aspartate aminotransferase, alanine aminotransferase and cholinesterase levels unaffected. A mixture of ethynylestradiol plus norgestrel in the mass proportion occurring in Microgynon produced the same effects upon gamma-glutamyltransferase and alkaline phosphatase as ethynylestradiol alone. Estradiol, the parent hormone of ethynylestradiol, lacked the inducing capability of the latter while ethynylpropargyl chloride induced gamma-glutamyltransferase and alkaline phosphatase so it was concluded the inducing effect of ethynylestradiol must be ascribed to the ethynyl radical. Progesterone, the parent of norgestrel, shared the latter's suppressive activity for gamma glutamyltransferase and alkaline phosphatase biosynthesis, and behaved like its derivative towards the other enzymes. PMID- 2603460 TI - [Interference of bisphosphonate in calcium determination using atomic absorption spectroscopy]. AB - The calcium determination by atomic absorption spectroscopy is impaired in samples which contain 1-hydroxyethylidene-1,1-bisphosphonate. We describe possibilities to avoid these bisphosphonate-mediated interferences of calcium measurement. PMID- 2603462 TI - [The determination of the reference range and the reference limits of the fructosamine test]. PMID- 2603461 TI - [The effect of postpartum blood collection on the health and liveweight development of calves and the use of neonatal calf serum (NCS) for the in vitro cultivation of mouse embryos]. AB - The influence of postpartal blood taking on health and growing of calves and the use of neonatal calf serum (NCS) for cultivation of mice embryos was investigated in 3 experiments with 134 calves. The results indicate, that the neonatal blood taking (max. 2 h p.p.) is without negative effects on health and growing of calves. It is possible to use the NCS like fetal calf serum (FCS) as additive in cultivation mediums for mice embryos. The utilization of NCS for cultivation of bovine embryos and for other laboratory purposes should be tested. PMID- 2603463 TI - [Comparison of the results of the fructosamine test done by two unrelated laboratories]. PMID- 2603464 TI - [On-line evaluation of the radioimmunoassay using the microcomputer KC 85/2]. PMID- 2603465 TI - [Cerebrospinal fluid cell enrichment using the sediment chamber and the absorption chamber with the use of polycation-layered slides]. PMID- 2603466 TI - [Preparation for the integration of the particle counter PS-4 into a laboratory with EDV]. PMID- 2603467 TI - The ontogeny of sexual dimorphism in the cranium of Bornean orang-utans (Pongo pygmaeus pygmaeus): I. Univariate analyses. AB - Based on a homogeneous sample of 212 individuals spanning all postnatal age periods, we examine the ontogeny of cranial sexual dimorphism in Bornean orang utans (Pongo pygmaeus pygmaeus) by means of univariate statistics. A distinct pattern emerges at the early juvenile stage and continues at all subsequent stages with males tending to exceed females in all cranial dimensions. In conjunction, starting at mid-juvenile stage, there is a strong tendency for an increase in number and strength of significant cranial sex differences, all of them in favor of males. Significant sex differences in the viscerocranium, reflecting stronger prognathism in males, emerge prior to those in the neurocranium. The total ontogenetic pattern of cranial sexual dimorphism in orang utans is remarkably similar to that of gorillas, except that there is no evidence of a sex difference in timing of the adolescent growth spurt in the orang-utan. As for other catarrhine species (Wood 1976), male variance of cranial dimensions tends to be greater than that of females, thus lending support to Leutenegger & Cheverud's (1982, 1985) model on the evolution of character dimorphism by means of variance dimorphism. PMID- 2603468 TI - Developmental relations between the weight of internal organs and somatic features of fetuses and newborns. AB - The paper contains results of investigations on statistical developmental interrelations between the weight of brain, heart, lungs, liver, spleen, kidneys, adrenal glands and thymus, and the total length, the crown-rump length and the body weight, and the circumference of head, shoulders, chest and abdomen of fetuses and newborns in the age from 17 to 43 weeks of life. The character and the force of the relations between the degree of the development of the weight of organs and the body dimensions was investigated by statistical methods on three levels. On the basis of the value of linear correlation coefficients, statistical relations were determined between the weight of the particular organs and the particular sometic features. The dependence between the particular organs and the complex of somatic features was determined on the basis on the multiple regression analysis. On the other hand the relation between two complexes of features, i.e. all organs and all somatic features was investigated with the help of canonical correlation coefficients. The analysis of results indicated that between the weight of internal organs and the somatic features in the fetal period there exists a statistical developmental relation. The developmental relations are most strongly marked between the 6th and the 10th months of intrauterine life, while in the 5th month of life and in postmature fetuses and newborns they are weaker. PMID- 2603469 TI - The formation of the proportions of the liver, spleen and kidneys in the fetal ontogenesis. AB - The paper discusses the formation of basic proportions of the liver, spleen and kidneys between the 21st and 43rd week of pregnancy. 433 fetuses and 941 newborns, selected from 632 fetuses and 1276 newborns, were tested. Measurements of the length, width and thickness of these organs have been taken to the accuracy of 0.1 mm on unpreserved fetuses and newborns within 24 hours after still births or deaths. As the organs under study are parenchymatous, the measurements were taken in their natural position inside the body cavity. The material has been divided into six developmental phases, i.e. from the 6th till the 10th lunar month. Individuals born in the 41st-43rd week were considered to be prolonged and included in the age category older than the 10th month (less than 10). The formation of the proportions of the organs in question has been considered from the viewpoint of a statistical analysis separately for the fetuses and newborns. The analysis of the results confirmed descriptive data available to date about a slightly different shape of these organs during the fetal period and showed the direction of changes occurring in the basic proportions of the organs. Following the comparison of these proportions with appropriate indices in adults, it is possible to predict a further direction of changes in the postnatal period. During the fetal period the organs under study take the shape of the ellipsis since the width-thickness dimensions dominate over the length dimensions. In the postnatal period the organs become slimmer. Significant differences in the size and proportions of the organs under study between the fetuses and newborns have been found in the fetal period. PMID- 2603470 TI - Standards of morphological development in fetuses and newborns as a method of defining fetal age. AB - Whenever the calendar age of the studied fetal material is not known we are bound to reconstruct it by replacing it with the developmental age. In this paper some common developmental standards used in the determination of fetal age are reviewed. The standards, as found in the relevant literature, are tested against a control group for their accuracy in predicting fetal age. The results indicate considerable discrepancy among the various standards. Further, the developmental ages defined by these standards often differ considerably from the known menstrual age. My own attempt to present a more reliable set of developmental standards is based on the analysis of three morphological features commonly used in biological assessment. Body weight, crown-heel length, and crown-rump length are measured in weekly termed groups representing the 20th-42nd weeks of intrauterine life. The accuracy of body weight and crown-heel length in predicting fetal age is tested both within and against a control group. Statistical analysis show no significant differences between the predicted and known fetal ages. These results indicate that body weight and crown-heel length are reliable developmental standards from which fetal age can be defined. PMID- 2603471 TI - The ontogeny of sexual dimorphism in the cranium of Bornean orang-utans (Pongo pygmaeus pygmaeus): II. Allometry and heterochrony. AB - Based on a homogeneous sample of 212 individuals spanning all postnatal periods, we examine the ontogeny of cranial sexual dimorphism in Bornean orang-utans (Pongo pygmaeus pygmaeus) by means of allometric analysis and in terms of heterochrony. The bivariate growth allometries of 20 cranial dimensions against basicranial length yield two major patterns. Confirming the null hypothesis, strong ontogenetic scaling, where growth regressions of both sexes fall along a single ontogenetic continuum, and where shape differences between adult males and females result from the extension of relative growth in the smaller females to larger size in males, is found in 10 cases. Ontogenetic scaling is particularly strong in proportions of (1) the neurocranium directly associated with brain size, (2) the orbital region, and (3) the dental arcade. In terms of heterochrony such a pattern most likely is the result of a process termed "time hypermorphosis", i.e. an extension of the growth period in time in males. The second major pattern seen in the remaining 10 cases shows a departure from ontogenetic scaling, with males exhibiting a significantly steeper slope than females. Departures from ontogenetic scaling, where size and shape are dissociated with adult males being disproportionately larger than adult females, are found in proportions of cranial regions directly associated with secondary sexual character development: prognathism, canine size, and cheek pad area. In terms of heterochrony such a pattern most likely is the result of a process termed "acceleration", i.e. the rate of shape change is increased in males. PMID- 2603472 TI - Lightmicroscopical investigations of the sublingua of Microcebus murinus (Cheirogaleidae, Lemuriformes) with remarks on the phylogenetic relations of the tree shrews (Scandentia) to primates. AB - The sublingua of Microcebus murinus was studied gross anatomically and light microscopically. The apex of the sublingua ends in two lobe-like projections separated by a distinct median cleft. The lobes exhibit at their oral, free margin tiny processes, but no "comb"-like specializations of intensely keratinized mucosa. At the ventral surface of the sublingua three longitudinally oriented keels or ridges are found; the mucosa of the keels is strongly keratinized, so that these structures maximize the rigidity of the undertongue. In none of the specimens examined was any trace of sublingual cartilage found; in the sublingua of Cheirogaleus (only one individual examined), the nearest relative of Microcebus, cartilage was also absent. The absence of sublingual cartilage and the incidental, irregular occurrence of cartilaginous elements in the sublingua of Tarsius and Tupaia indicate that the sublingual cartilaginous skeleton is not a derivative of the hyoid arch. It is a newly developed supporting structure which does not regularly occur. A sublingua occurs only in prosimians and Tarsius; whether the fimbria linguae of the Hominoidea is the homologue of a sublingua is still disputable. The exclusive occurrence of a sublingua in prosimians and Tarsius indicates a phylogenetic relationship between these two groups and Tupaia. The "Tupaia-problem" concerns the origin of primates and from this point it derives its general importance. At present we are far from a final solution; a definite answer cannot be expected before sufficient fossil records are available which document conclusively the historical paths of the origin of primates. PMID- 2603473 TI - Genetic studies in four populations of the northern Aegean Sea, Greece. AB - A total of 945 non-related individuals from four isolated population groups from the Northern Aegean Sea (Greece)--Alonissos, Oxilithos, Skopelos, and Glossa, has been typed for 16 polymorphic systems of the blood, namely A1A2B0, MNS., Rhesus (C, c, Cw, D, E, e), Kell, Duffy (a,b), Kidd (a); Hp, Tf subtypes, Gc, Gm (1, 2, 3, 5, 13), Km (1); aP, AK, PGM1, EsD, and 6-PGD. The distribution of phenotype and gene/haplotype frequencies shows a considerable interpopulational variability, which is discussed considering the history of these populations as well as the impact of locally acting microevolutionary factors such as drift and founder effects. The average coefficient of gene diversity GST comes to 0.0147, whereas Wahlund's variance is on average 0.0154, and Wright's Fst = 0.0147. Genetic distance analysis reveals a pattern of similarities, which is in conformity with the history of the populations under study. PMID- 2603474 TI - [Medicine in relation to external constraints]. PMID- 2603476 TI - [Control of cardiac pacemakers. Where, when and how?]. PMID- 2603475 TI - [Pattern of distribution of pre S and S coded viral envelope proteins of hepatitis B virus on the molecular level in serum and liver tissue of chronic HBsAg carriers]. PMID- 2603477 TI - [Treatment of type I diabetes mellitus with continuous subcutaneous insulin infusion: indications and quality control]. PMID- 2603478 TI - [Superfluous clinico-chemical studies, a contribution to rational clinico chemical diagnosis]. PMID- 2603479 TI - [Superfluous diagnosis in pneumology]. PMID- 2603480 TI - [Essential and superfluous tests in the diagnosis of acute appendicitis]. PMID- 2603481 TI - [An internist at the accident site--what should be done?]. PMID- 2603482 TI - [The treatment of renal anemia]. PMID- 2603484 TI - [Urinary tract infections, antibiotics]. PMID- 2603483 TI - [Prophylactic measures for preventing renal osteodystrophy]. PMID- 2603485 TI - [Cause of death following heart valve replacement]. PMID- 2603486 TI - [Frequent diagnostic errors in findings relating to the kidney and urinary tracts]. PMID- 2603487 TI - [Frequent diagnostic errors in diseases with joint symptoms]. PMID- 2603488 TI - [Role of HIV-2 infection in West Germany and the pathogenicity of the virus]. PMID- 2603489 TI - [Role of macrophages in the pathogenesis of HIV infection]. PMID- 2603490 TI - [Management of HIV infected and AIDS patients in Hesse]. PMID- 2603491 TI - [Clinical aspects of arthroses]. PMID- 2603492 TI - [Responsibilities of the surgeon in kidney transplantation]. PMID- 2603493 TI - [The macrohematuria alarm signal--what should be done?]. PMID- 2603494 TI - [Possibilities and limits of chemotherapy in multi-modality treatment of urinary bladder cancer]. PMID- 2603495 TI - [Which patients should be excluded from airplane travel?]. PMID- 2603496 TI - [Drugs and fitness for flying]. PMID- 2603497 TI - [Which preventive vaccinations are recommended for foreign travel?]. PMID- 2603498 TI - [Travel diarrhea--prevention and therapy]. PMID- 2603499 TI - [Treatment of hyperlipidemia in diabetes mellitus and hypertension]. PMID- 2603500 TI - [Qualitative and quantitative aspects of sports and high risk patients]. PMID- 2603502 TI - [Muscle pain in myopathies]. PMID- 2603501 TI - [Muscle pain in rheumatic diseases]. PMID- 2603503 TI - [30 years' spontaneous recording systems of German physicians--results and experiences]. PMID- 2603504 TI - [Comprehensive detection of severe, potentially life-threatening drug side effects]. PMID- 2603505 TI - [Detection of drug side effects at the Heidelberg Medical Clinic]. PMID- 2603506 TI - [The safety profile of anti-rheumatic drugs in long-term use]. PMID- 2603507 TI - [Side effects of oral contraceptives in internal medicine--a current problem]. PMID- 2603509 TI - [Side effects caused by ofloxacin: status of knowledge before legalization and changes caused by spontaneous reports thereafter]. PMID- 2603508 TI - [Depot neuroleptics in indications for tranquilizers: administration forms and risk in neurologic practice]. PMID- 2603510 TI - [Dialysis and related procedures in the treatment of acute renal failure]. PMID- 2603511 TI - [Indications and choice of procedure in artificial kidney treatment of chronic renal failure]. PMID- 2603512 TI - [Long-term results of artificial kidney treatment of terminal renal failure]. PMID- 2603513 TI - [Break with traditions! Different working hours makes for better care]. PMID- 2603514 TI - [Shorter working hours]. PMID- 2603515 TI - [The last days with my father]. PMID- 2603516 TI - [Dancing on the table]. PMID- 2603517 TI - [From cleaning to defibrillation--here 34 independent nurses manage everything]. PMID- 2603518 TI - [Work program: improved working hours with local solutions]. PMID- 2603519 TI - [Club established--against all odds]. PMID- 2603521 TI - [Health care in practice--breakfast served in the classroom]. PMID- 2603520 TI - [Investigation took a long time. Ombudsman criticizes National Social Welfare Board. Interview by Jan Thomasson]. PMID- 2603522 TI - [Peggy and Inger invite you in: come and sample the health center's food]. PMID- 2603523 TI - [Child health center in Rosengard: refugees are our best patients. Interview by Tord Ajanki]. PMID- 2603524 TI - [Ilona, immigration secretary: we believe in bacteria, second in God's punishment. Interview by Tord Ajanki]. PMID- 2603525 TI - [Deliberation on wage policy]. PMID- 2603526 TI - [Do you really believe in 6-hour days Margot Odman?. Interview by Kay Nyman]. PMID- 2603527 TI - [A private care facility starts now--nurses will have a lot of responsibility]. PMID- 2603528 TI - [Nurses in Tromso keep manager's role--physicians on the war-path]. PMID- 2603530 TI - [General Director urges renewal of Social Welfare. Interview by Viveka Holertz]. PMID- 2603529 TI - [SHSTF's lawyer comments on the National Social Welfare Board's changed statutes]. PMID- 2603531 TI - [Gentle start for newborn infants gives new life to the ward]. PMID- 2603532 TI - [Worried nurses discuss care for the aged]. PMID- 2603533 TI - [Permanent nursing instructors teach via video]. PMID- 2603534 TI - [Priority setting in health care]. PMID- 2603535 TI - [School Board: strike is based on a misunderstanding]. PMID- 2603536 TI - [Your salary]. PMID- 2603537 TI - [Inger Ohlsson after 3 years of chairperson: evaluation and wages are the most important during terms. Interview by Viveka Holmertz and Kaj Nyman]. PMID- 2603538 TI - [Educated alternative medicine practitioners provides safeguards in treatments]. PMID- 2603539 TI - [A leader for health care and service]. PMID- 2603540 TI - [Care for the aged in transformation: Tomas prepares for transition now already. Interview by Kaj Nyman]. PMID- 2603541 TI - [Fight over hospital leadership continues in Tromso]. PMID- 2603542 TI - [SSAMK (Nurses and Assistants against Nuclear Weapons) continues the fight against nuclear weapons, for peace. Interview by Jan Thomasson]. PMID- 2603543 TI - [Nurse Birgit retrained herself into clown Biggan. Interview by Britta Nilsson]. PMID- 2603544 TI - [Nurses' knowledge cannot be formulated into scientific language. Interview by Viveka Holmertz]. PMID- 2603545 TI - The role of the endothelium on calcium-entry blockade in coronary vasospasm. AB - Calcium-entry blockers are widely used for the treatment of coronary vasospasm. The mechanisms responsible for coronary vasospasm are still uncertain, but ultimately involve contraction of the vascular smooth muscle of the large coronary artery. The direct constrictor responses of coronary smooth muscle can be reduced by the inhibitory effect of endothelium-derived relaxing factor(s). The absence of endothelium can augment the response of vascular smooth muscle to vasoconstrictor stimuli, but may also modify the potency of calcium-entry blockers. The role of calcium-entry blockers on the endothelial function is not known. Nisoldipine is a new compound from a series of calcium-antagonistic dihydropyridines. The aim of the present experiments was: 1. to determine the effect of nisoldipine on contractions of large coronary arteries evoked by possible mediators of coronary vasospasm and 2. to determine whether or not the presence of endothelial cells affects the response to the calcium-entry blockers. Rings of canine coronary arteries with and without endothelium were studied in organ chambers filled with modified Krebs-Ringer bicarbonate solution. The rings were incubated for 45 min either in control solution or in the presence of increasing concentrations of nisoldipine (10(-10) to 10(-6) M). In the concentration range of 10(-9) to 10(-7) M nisoldipine inhibited the contractile responses evoked by allagents: KCL (10 to 80 mM), 5-hydroxytryptamine (10(-9) to 10(-6) M), ergonovine (10(-9) to 10(-6) M), norepinephrine and phenylephrine (10( 9) to 10(-4) M both in the presence of propranolol 5 X 10(-6) M). Nisoldipine was more potent in inhibiting contractions to potassium chloride in the absence of the endothelium. By contrast, in case of 5-hydroxytryptamine or phenylephrine, nisoldipine was less potent in the absence of the endothelium. Similar results were obtained in the case of ergonovine and norepinephrine. The hypoxic contractions were reduced by nisoldipine in a concentration dependent manner. Nisoldipine inhibited the platelet-induced contractions both in the presence and the absence of endothelium. The present study demonstrates that the dihydropyridine, nisoldipine, is a potent inhibitor of contractions of the smooth muscle of large coronary arteries caused by a number of putative mediators of coronary vasospasm including catecholamines and products released by aggregating platelets. It also prevents hypoxic contractions of coronary vascular smooth muscle. PMID- 2603546 TI - [A not-previously described hereditary neurological disease with a deficiency of sialic acid, galactose and N-acetylglucosamine of plasma glycoproteins]. AB - We report on five girls (including monozygotic twins) with a newly recognized disease comprising severe neurologic disturbances, variable hepatomegaly, abnormal subcutaneous fat distribution and skeletal anomalies. The neurologic picture was characterized by moderate to severe psychomotor retardation, alternating internal strabismus , hypotonia, hyporeflexia and ataxia. Biochemical investigations showed a number of abnormalities such as tubular proteinuria, slightly increased serum transaminases, hypoalbuminemia, hypo-beta lipoproteinemia and decreased serum thyroxine-binding globulin. Moreover there was retinitis pigmentosa, cerebellar hypotrophy and electrophysiologic evidence for a peripheral neuropathy. However, histologic examination of a nerve biopsy in one of the patients failed to show myelin abnormalities. On the other hand, abnormal lamellar inclusions were found in the lysosomes of some Schwann cells and of liver tissue as well. Additional investigations in four patients revealed a deficiency of sialic acid, galactose and N-acetylglucosamine of plasma glycoproteins. Enzymatic analysis of serum suggested a deficiency of an N-acetyl glucosaminyltransferase. Remarkably, the (healthy) fathers but not the mothers presented the same carbohydrate deficiencies of plasma glycoproteins albeit to a much lesser degree. The mode of hereditary transmission of this disease remains unclear; the possibility of X-linked inheritance is under investigation. PMID- 2603547 TI - [Evoked cortical activity to sounds of differing signal meaning in young and elderly subjects]. AB - In elderly people, in comparison with the young ones, the latency of wave P300 is increased in response to all applied acoustic signals, the amplitude of P300 is lower only in response to significant stimuli. No age changes of the wave N150 parameters are noticed. P300 (or N150) wave amplitude depends on signal significance of the sound; it is the lowest in response to significant stimuli and the highest to the ignored ones. Possible reasons of this paradoxical phenomenon are discussed. Preferential participation of different stages of cortical information processing is determined by the difficulty of perceptive task solution. Cortical electrical reaction to separate stimuli is significantly determined by the context of the information perceived in the given period, creating psychological state of the personality. PMID- 2603548 TI - [The time of a complex sensorimotor choice reaction in subjects with differing functional mobility of the nervous processes]. AB - In 246 subjects (men, mean age--21 years) differing by the level of functional mobility (I-IV), statistically significant differences were found of mean values of latencies of complex sensorimotor reactions of choice (differentiation by meaning). Computation of Pearson correlation coefficients revealed significant negative connections between characteristics of functional mobility and values of latencies. On the basis of these data it is possible to consider the value of the latency of complex semantic reactions of choice as an information index of functional mobility of nervous processes. PMID- 2603549 TI - [The significance of interhemispheric asymmetry in the development of compensatory processes in the human brain]. AB - For more precise definition of the role of hemispheric interconnections in mechanisms of human CNS compensation the intercentral relations of the electrical activity of the left and right cerebral hemispheres were studied on physiological model of focal interhemispheric asymmetry. Spectral-coherent EEG characteristics of 36 patients with tumoral damage of one hemisphere were studied in condition of chronic (prior to operation) and acute (early terms of postoperative period) brain decompensation. In was shown that the reorganization of the structure of the EEG intercentral relations correlated with definite stages of CNS compensatory processes and that the character of hemispheric interconnections depended on the lateralization of the damage focus. The primary role was revealed of the degree of the left (dominant) hemisphere preservation in restoration of normal pattern of the interhemispheric asymmetry of the coherence of human brain electrical processes. PMID- 2603550 TI - [The evaluation and prognosis of the psychophysiological status of a human operator]. AB - In experiments on 56 healthy subjects (18-20 years old) the quality of their activity was determined during compensatory watching the mark at complicating regimes of work. Depending on the difficulty of the task five groups of subjects were singled out with optimum working capacity in one of four working conditions: normal, ordinary and strenuous work, model of stress situation. It is established that the change of the number of significant correlative connections between main parameters of psychophysiological state of man-operator reflects the condition of his functional systems. On the basis of computation of total range of organization values of both R-R intervals of the ECG and duration of expiration, the success of the man-operator work in complex conditions of activity is predicted. PMID- 2603551 TI - [Dynamics of temporal parameters of sensorimotor reactions in relation to the type of human movement]. AB - The study was conducted on nine right-handed male subjects 20-24 year old and consisted of two series. In the first series one warning signal in the form of one of the digits (from 1 to 8) was successively presented to the subjects on the display and then four trigger signals which required either simple pressing of the push button (an arrow with a dot) or its holding during 0.5 s (two arrows) by the right or left hand depending on the arrow direction. The digit corresponded to one variant of signals succession. Each variant was repeated randomly among other variants 15 times. In the second series instead of arrows asterisks were presented. Reaction time and duration of push button holding were recorded. Two regularities were observed: significant decrease of RT in the series of reacting by memory and successive decrease of RT in accordance with the decrease of the number of the remaining signals observed in both series. In the first series RT successively decreased by 35-40 ms, in the second one-by 16-20 ms. It is supposed that the difference in RTs between series characterizes the time of signal structure analysis, while the difference in RTs within one block of signals in the second series-the time of extraction of selected motor program from memory. PMID- 2603552 TI - [The invariance of subjective time scales]. AB - Organization of subjective time scales was studied by various methods of duration scaling (reproduction, fractionation, multiplication, evaluation, measuring and cross-model selection). Computation of linear correlation coefficients between physical time and its subjective expression for various methods of scaling in different coordinate systems allows to make a conclusion about a degree form of psychophysical dependence. The value of function degree index varies in the range of 0.80-0.88 for verbal evaluation and 0.93-1.07 for other methods. The concept is suggested about the "active" and "passive" time. PMID- 2603553 TI - [The role of signal and motivational links of a conditioned reflex in the initiation of instrumental movements in dogs]. AB - Alimentary instrumental conditioned reflex (CR) was elaborated in dogs to light flashes (I series), electrostimulation (ES) of the hippocampus (II series) and the hypothalamus (III series). Nonreinforced ES of the hypothalamus, amygdala, hippocampus and septum reproduced pressings on the pedal to the least extent in the I series (17-40% of trials), increasing in the II-nd one up to 40-87% during stimulation of the lateral hypothalamus, medial amygdala and contralateral hippocampus. In the III-rd series the number of pressings increased statistically significantly in comparison with the I-st series for most structures. Probably, besides the artificial increase of motivation during ES of the limbic structures which took place in all series, in the II-nd and III-rd series significance for movement reproduction was acquired by CR generalization appearing due to close interconnection of the structures. In this phenomenon connections (evaluated by the EPs) from the tested structures to the initially signal one are important. PMID- 2603554 TI - [Can the function of the extirpated amygdaloid complex be compensated for by the transplantation of embryonic nerve tissue?]. AB - In 20 white rats bilateral coagulation of the amygdalar complex was produced; on the fifth day to one half of them transplantation was performed by introducing stereotaxically on the left side 0.2-0.5 mm3 of the brain embryonal tissue from the corresponding area of the amygdala of 20-days embryo; in control saline was administered. After two months the rats were sacrificed to determine the activity of antiradical defense by superoxide dismutase (SOD) and the level of lipids peroxide oxidation (LPO) in the cerebral cortex. The transplantation decreased LPO even more and increased SOD as compared to amygdalectomy, e. i. caused still greater deviations from the norm (in this meaning--paradoxal effect), what apparently corresponds to intensification of adaptative-compensatory processes caused by amygdalectomy. The transplantation did not reverse the rats behaviour to the initial one and did not eliminate memory defect in the test of conditioned reaction of passive avoidance (like pyrazetam); it had different direction influence on "drinking under current" in conflict situation, only in particular cases approaching it to the norm. PMID- 2603555 TI - [The participation of CCK-8-ergic mechanisms in the regulation of emotional behavior in rodents]. AB - Effects of CCK-8 receptor agonists caerulein and pentagastrin and CCK-8 receptor antagonist proglumide on exploratory and locomotor activity of mice and rats were studied. Systemic administration of caerulein (500 ng/kg 1 mcg/kg) decreased significantly the exploratory activity of mice in elevated plus-maze. This anxiogenic-like action of caerulein was attenuated by acute pretreatment with proglumide (1 and 15 mg/kg) but not with diazepam (up to 0.75 mg/kg). Proglumide slightly increased the exploratory activity of rats in plus-maze; on the other hand, caerulein and pentagastrin potently decreased the measures of exploration in this test. Caerulein (10-100 mcg/kg) and proglumide (1 and 15 mg/kg) inhibited 3H-pentagastrin binding in mice brain in in vivo experiments. The data obtained indicate that CCK-8-ergic mechanisms in brain play an important role in the generation of anxiety states in rodents. PMID- 2603556 TI - [Behavioral correlates of aggressive motivation in male mice]. AB - The behaviour was studied of male mice of CBA/Lac and C57BL/6j lines near transparent perforated partition in reaction to syngeneic partner which was in adjacent department of the common cage. The number of approaches to the partition and total time of staying near it during testing were used as behaviour parameters. Then the partition was removed and the success or defeat of each individual in agonistic collision and parameters of aggressive reaction of the winner male mouse were fixed. It turned out that future winners spent significantly more time near the partition than future losers. By the correlative analysis reliable interconnections were established between individuals activity near the partition (number of approaches or total time of staying) and intensity of aggression (number or total time of attacks) which reflects the level of the aggressive motivation. Variation is observed of individual correlating parameters depending on animals genotype and conditions of their keeping. PMID- 2603557 TI - [Regression analysis of an instrumental conditioned tentacular reflex in the edible snail]. AB - Regression analysis revealed the opportunity of approximation with exponential mathematical model of the learning curves of conditioned tentacle reflex. Retention of the reflex persisted for more than three weeks. There were some quantitative differences between conditioning of the right and the left tentacle. There was formation of the reflex in every session during spring period, but there was no retention between sessions. The conditioned tentacle reflex may be employed in neuropharmacological studies. PMID- 2603558 TI - [Multineuronal cortical activity in dogs with a defensive instrumental conditioned reflex]. AB - By methods of correlation analysis, interrelations were studied of neurones with high, mean and low amplitudes of spikes singled out by amplitude principle from background multineuronal activity of the motor and somatosensory cortical zones, recorded by chronically implanted semi-microelectrodes in dogs. In trained animals, a high positive correlation was observed of singled out neurones discharges, particularly between the neurones with low and mean amplitude of spikes. By the method of cross-interval histogram, dependent relations were revealed of the neurones with different amplitude characteristic mainly of one sided excitatory character. PMID- 2603559 TI - [Neuronal specialization of the motor cortex in normal rabbits and following destruction of the visual cortex]. AB - The activity of neurones of the anterolateral part of the motor cortex in food acquisition behaviour was compared in two control rabbits and in three rabbits after the operation of bilateral ablation of the striatal cortex. In two of three operated rabbits the pattern of behavioural specialization lost considerably the specificity peculiar to the motor cortex (predominance of G-neurones activated in grasping of food), approaching (but not becoming identical) the pattern of specialization of the visual cortex neurones: the number of G-neurones decreased in a half, and the number of L-neurones (activated in connection with the acts of instrumental food-acquisition behaviour which animals were trained to in the experimental cage) was doubled. Changes of the activity were significantly less expressed in the third operated rabbit. The number of the neurones activated in food-acquisition behaviour in operated rabbits in comparison with the control ones was reduced in the upper layers of the cortex and increased in the lower layers. The resemblance is discussed of the basic processes of animals learning and behaviour recovery. PMID- 2603561 TI - [Variability in the morphofunctional differentiation of the CNS in a heterogeneous population of laboratory mice]. AB - The psychomotor maturation rate was studied in a heterogeneous stock of laboratory mice. Mean ages of several innate reflexes formation were compared for two groups of animals which represented extreme variants of brain weight phenotypes when adult. Mice with measured brain weights, by least 0.67 standard deviation higher (H) or lower (L) than the average for the whole population, reveal substantially different psychomotor development, the H-group appearing to be more advanced. This observation is at variance with those obtained using the lines of laboratory mice selectively bred for high and low brain weight. The apparent inconsistency of the two experiments may reflect the relative dominance of environmental (heterogeneous stock) or genetic (selected lines) factors, as well as occasional fixing of certain alleles in process of selection. PMID- 2603560 TI - [The modelling of theta rhythm regulation by an increasing afferent inflow in septal slices in vitro]. AB - The aim of the work was the modelling in vitro of the condition of increased afferent inflow, which in the intact septum results in an increase of population of theta-bursting units, their synchronization and shift to a higher frequency of the bursts, with corresponding changes in the hippocampal electrical activity. Neuronal activity was recorded extracellularly in the medial septal nucleus and vertical limb of the nucleus of diagonal band (MS-DB) in guinea pig septal slices. Electrical stimulation in the medial part of horizontal limb of DB evokes initial period of suppression of spontaneous activity in 85% of the neurones. This low-threshold, rapid inhibition has variable duration (20-280 ms) in different units at low intensities of the stimulating current. With increased intensities of stimulation this inhibitory phase in majority of units is gradually or by steps shortened, though in some units with initial short inhibition it is not changed. As a result the variability of initial inhibitory period between units is decreased and centered around 30-60 ms. Many units with single-spike background activity developed postinhibitory burst responses at various levels of stimulating current. The spontaneously bursting MS-DB units always responded by resetting of their background bursts. In total 58% of all recorded neurones generated evoked bursts under condition of increased afferent inflow. PMID- 2603562 TI - [The role of dopamine and serotonin in modulating the defensive behavior of the edible snail]. AB - Dopamine application in concentration of 10(-5)-10(-6) M into saline around the snail CNS leads to decrease of excitability of LPa7 neurone which is presynaptic in relation to defensive behaviour command neurones, and to decrease of amplitude of monosynaptic excitatory postsynaptic potential (EPSP) in the command neurones elicited by intracellular stimulation of LPa7 neurone. Besides, the dopamine causes a decrease of summated EPSP amplitude in the studied neurones in response to intestinal nerve stimulation (70% in average), a change of rest potential towards hyperpolarization for 6-8 mV, a reduction of the command neurones input resistance (20% in average). The described influences can lead to a general increase of the threshold of defensive system reaction to stimulation. Dopamine action on the defensive behaviour command neurones is significantly weakened in serotonine presence. Against the dopamine background, the efficiency of serotonine influence on the value of EPSP in command neurones in response to testing stimulus is reduced. According to the obtained data, a conclusion is made that interrelation of dopamine and serotonine concentrations can be a base for formation of behaviour choice in snail. PMID- 2603563 TI - [The phenomenon of conditioned suppression of the generation of action potentials in isolated neurons of the edible snail]. AB - A conditioning procedure was performed with isolated identified neurones of Helix pomatia. Depolarizing intracellular electrical pulses producing spike generation were used as conditioned and unconditioned stimuli (CS and US). The conditioned response consisted in the depression of spike generation evoked before learning by the presentation of CS. These conditioned responses persisted during 12-30 min after 3-5 trials of associated CS-US. An additional stimulus was used to test the specificity of associated learning concerning the stimulated loci of electroexcitable membrane. The results showed the locality and specificity of conditioning. The depression of action potentials evoked by the associated presentations of CS-US is suggested to be a form of modification of initial response to CS, typical for interneurones if the CS is of suprathreshold intensity. PMID- 2603564 TI - [A biorhythmologic approach to evaluating forced swimming as an experimental model of a "depressive" state]. AB - Rhythmical structure of forced swimming was studied on rats. Reserpine (1 mg/kg, 24 h before testing), clonidine (150 mkg/kg) and prolonged repeated striatal stimulation induced behavioural depression with reorganization of swimming rhythm and increase of short cycles (less than 6 s) of immobility. After chronic administration of antidepressants (imipramine, amitriptyline, niamid, 10 mg/kg/day, during 14 days), on the contrary, the number of these cycles diminished, while the number of active swimming cycles increased. Chrono biological "index of depression" is suggested to express more exactly behavioural depression and specific activity of antidepressants than usual registration of immobility time. PMID- 2603565 TI - [Comparative characteristics of short-term plasticity in the hippocampus of adult and developing rats]. PMID- 2603566 TI - [A transistor-based portable electroplethysmograph]. PMID- 2603567 TI - [Stochastic simulation of the instrumental reflex in probability learning]. AB - A method of computer imitation modelling is worked out of the process of instrumental reflex elaboration allowing to prognosticate the rate of learning at various combinations of probabilistic medium parameters and individual properties of the learning subject. By means of imitating modelling it is easy to find out the localization of the optima and pessima zones in the space of parameters influencing the learning. For building the model the empiric data are not required--they are used only for checking the obtained results. Therefore the conformity obtained with the literature data and the results of own studies allows to suggest that firstly, the worked out model possesses a good forecasting power and secondly, it can be used for studying such conditions of learning for which the appropriate experimental material is not yet collected. PMID- 2603568 TI - [A method for studying depth vision in an experiment in cats]. PMID- 2603569 TI - [The strength of evidence of the food inspection after the Chernobyl accident proven by whole body measurements of Basel students]. AB - The radioactive contamination of the food consumed by the inhabitants of Basel after the Chernobyl fallout has been continuously controlled by our laboratory. The activity of ingested Cs-137 has been estimated and is compared here with the activity obtained through whole body counts. The satisfactory correlation between calculated and observed body activities enables an exact estimation of the people's doses applying the same model and demonstrate the reliability of the food control analysis. PMID- 2603570 TI - [Use of solid phase extraction for rapid sample preparation in the determination of food constituents. I. Quinine in beverages]. AB - A routine method was developed for the determination of quinine in spirits and alcohol-free beverages. Using ion pair chromatography quinine was separated from interfering substances by high-performance liquid chromatography on a RP 18 phase and analysed by UV and fluorescence detection. In contrast to the analysis of alcohol-free beverages, sample preparation was necessary in the study of alcoholic beverages. Solid-phase extraction on phenyl sorbens was found to be a rapid, specific and simple technique. PMID- 2603571 TI - Rapid determination of tyramine in fish feed and slaughter offal by HPLC using coulometric detection. AB - Fish feed and slaughter offal products may contain decomposition compounds such as biogenic amines. Owing to their harmful effects on animals fed with such products, there is a need for determining the amine content. In the work a simple and fast HPLC method, based on coulometric detection (EC) measuring only tyramine, was developed for routine quality screening. The samples were extracted with 0.4 mol/L perchloric acid and analysed directly by HPLC using a mobile phase of 0.2 mol/L potassium dihydrogen phosphate in water at pH 3. Tyramine was detected using a coulometric detector consisting of two analytical cells, the first one at 0.4 V and the second at 0.7 V. The calibration was linear over the range 4.52 to 452 ng/ml. The minimum detectable quantity was 10 pg/20 microliters. The reproducibility and the recoveries were high. Comparison of the tyramine content measured by EC or derivatization followed by ultraviolet detection showed that both methods gave similar results. HPLC using EC is a fast and sensitive method for analysing tyramine reliably in fish feed and slaughter offal samples without any time-consuming derivatization steps. PMID- 2603572 TI - [Effects of scopolamine on delayed matching and non-matching to sample responses in T-maze in rats]. AB - The present study was designed to investigate the effects of scopolamine (SCP; 0.25 and 0.5 mg/kg, ip) on delayed matching and non-matching to sample (DMTS and DNMTS) responses in T-maze in rats. The groups consisted of the animals (N = 14) trained on the DMTS task with a short (3 min) intertrial interval (ITI), those (N = 12) on the DNMTS task with the short ITI, and those (N = 25) on the DNMTS task with a long (20 min) ITI. The results showed that (1) the DMTS task required a significantly larger number of trials to acquire than the DNMTS task, (2) the decay of performance with delay between information and choice runs was more pronounced in DMTS than in DNMTS, (3) the number of correct choices was smaller in the DNMTS responses with the short ITI than in those with the long ITI, (4) the disruptive effects of SCP were more marked in the DMTS than DNMTS responses, and (5) the effects of SCP in the DNMTS responses with the short ITI were not different from those in the responses with the long ITI. These results were discussed in terms of innate response (win-shift and win-stay) strategy, and working and reference memory components. It was concluded that SCP exerted the detrimental effects on both working and reference memory components. PMID- 2603573 TI - [Changes in 5-HT2 receptor density induced by repeated treatment with 5-HT uptake inhibitor or 5-HT agonist]. AB - It has been known that many antidepressant drugs which have serotonin (5-HT) antagonistic activities and 5-HT antagonists can induce the reduction of 5-HT2 receptor binding by their acute or successive administration. We investigated the effects of repeated treatment with 5-HT agonists on 5-HT2 receptors in rat cerebral cortex. We used citalopram as selective 5-HT uptake inhibitor, 5 hydroxytryptophan as 5-HT precursor, and 5-methoxy-N,N'-dimethyltryptamine as 5 HT2 agonist. The 5-HT2 receptor density was decreased by repeated treatment with these respective drugs. So it may be supposed that the reduction of 5-HT2 receptor binding is induced not only by 5-HT antagonists but also by 5-HT agonists. PMID- 2603574 TI - [Relationship between pharmacological action of phencyclidine and serotonin-2 receptor]. PMID- 2603575 TI - [Reconstruction of brain function by transplantation of catecholamine producing cells]. PMID- 2603576 TI - [Prosthesis loosening caused by infection of the hip joint. Current status and personal procedures in indications for primary and secondary exchange surgery]. AB - More than 50,000 hip-joint endoprostheses are annually inserted in the FRG. Surgery for replacement of prostheses has, consequently, grown in frequency. Reported in this paper are 27 operations for replacement of hip-joint prostheses that had become necessary for infectious problems. Follow-up checks confirmed for 14 of 27 patients sufficient control of infection, ability to walk, and tight position of prosthesis. Replacement should be performed in two surgical sessions, since a short-time Girdlestone situation without extension treatment or immobilisation is properly tolerated by patients with walking capacity, and the benefit of infection control should be the primary consideration. PMID- 2603577 TI - [Early functional treatment of rupture of the fibular ligament with a personally developed ankle splint]. AB - The inversion trauma of the ankle joint is one of the most important and frequent injuries. The treatment of recent rupture of the fibular ligament is now a point for discussion. Operative or conservative treatment is possible. The clinical evaluation of instability requires radiological control and stress test. With a new ankle splint we reduce pathological inversion of the ankle joint, so that we introduce a functional treatment. Our experience with this method will be demonstrated. 45 patients more than a half year after trauma reported good-to excellent results. The objective evaluation shows in 95% good-to-excellent results. A secondary ligament reconstruction was not necessary. PMID- 2603578 TI - [Injuries in occupational accidents]. AB - Evaluation of 3,096 accidents occurred during occupational activity in industry reveals the following results: most of the injuries of men are more serious than these of women. Ranking the injured parts of the body shows that injuries of the hand are most frequent. Moreover ranking the injured parts of the body as well as the nature of injuries reveals that there are notable differences between the two sexes. PMID- 2603579 TI - [Iatrogenic arteriovenous fistula of the popliteal artery following arthroscopic meniscectomy]. PMID- 2603580 TI - [Lateral subtalar dislocation of the foot]. PMID- 2603581 TI - [Post-traumatic varus deformity of the tibia. Correction by osteoclasia and callotaxis]. PMID- 2603582 TI - [C-reactive protein in the maternal serum and risk of maternal infection in premature rupture of the fetal membranes and threatened premature labor]. AB - For diagnosis of ascending intra-uterine infections, regular controls of the serum CRP levels were carried out in 129 patients with premature rupture of membranes and impending premature labour. The height of the maternal CRP level and the simultaneously determined leucocyte counts and band counts were compared with the peripartal fever morbidity (intrapartal fever, puerperal fever). It was established that patients who had a prepartal CRP level of 10 mg/l or more suffered febrile complications more frequently (fever morbidity 18.2%) than females in whom such high CRP values did not occur (fever morbidity 3.4%). Similar correlations existed between the other parameters tested and the fever morbidity, and subclinical intrauterine infections were recognized with higher reliability if CRP, leucocyte count and band count had been determined in combination. PMID- 2603583 TI - [C-reactive protein in the maternal serum and risk of fetal infection in premature rupture of the fetal membranes and threatened premature labor]. AB - In order to find out whether, in the framework of our obstetrical management, determinations of the C-creative protein (CRP) in maternal serum enables recognition of incipient intra-uterine infections, regular controls of the CRP level were performed in 129 patients with premature rupture of membranes and impending premature labour. The maternal CRP levels and the simultaneously determined total leukocyte counts and band counts were compared with the frequency of neonatal infectious diseases up to the 3rd day of life. None of the infants were affected whose mothers never had values above 10.0 mg/l. If he maternal CRP values exceeded the 10.0 mg/l limit, then 6.3%-57.1% of the newborns were affected depending on their birth weight. Therefore, the prepartal CRP diagnosis can, especially in infants with low birth weight, help to determine the risk of infection. PMID- 2603584 TI - [Modification of the penetration rate of human spermatozoa in the zona pellucida free hamster oocyte system by the use of polyclonal and monoclonal antibodies to human sperm]. AB - Incubation of human spermatozoa with polyclonal anti-sperm antibodies from sterile females reduced the penetration rates in the zona-pellucida-free hamsteroocyte assay significantly. Twelve sera having titers from 1:4,096 to 1:64 were used. Fifty-three ejaculates from men with normozoospermia were tested. A few of the ejaculates used were classified as slightly pathological showing asthenospermia. At an average titer 1:860 the reduction of penetration rate was about 49% (range 9-90%). The degree of reduction was dependent on the agglutination titer of the test serum, the presence of immobilizing antibodies, the amount of antiserum added, and on the quality of the ejaculates to a minor extent. The penetration rate of human spermatozoa in zona-pellucida-free hamster oocytes was reduced by 4 monoclonal anti-sperm-antibodies (A-24, B-20, III,3, and VII-5) out of 6 tested. The other 2 (VI-1 and VI-16) left the penetration rates virtually unchanged. The extent of penetration rate reduction depended on the concentrations of antibodies A-24, B-20, III-3, and VII-5; if undiluted, they produced a significant reduction of penetration rates, the largest average reduction being almost 50% with undiluted antibody A-24. Decreasing concentrations of the monoclonal anti-sperm-antibodies resulted in significantly smaller reductions of sperm penetration rates. The reason for the reduced penetration rates observed may be a blockage of receptors on the sperm surface by the named monoclonal anti-sperm-antibodies. This can inhibit enzyme reactions of the spermatozoa, or interfere with the interaction between oocyte and spermatozoa membranes. It is noted that only the antibody III-3 caused agglutination of human spermatozoa in the micro-sperm-agglutination and immobilization test. Therefore, the agglutination or immobilization of spermatozoa may not be held responsible for the reduced penetration rates after addition of monoclonal antibodies, as opposed to the findings with polyclonal antibodies. PMID- 2603585 TI - [Magnesium deficiency caused by epirubicin/cisplatin]. AB - In 19 patients receiving a cytostatic therapy with epirubicine and cisplatinum, 31 times in total the renal loss of magnesium was determined using the colorimetric xylidile-blue-method. 16 patients, whose magnesium input postoperatively was equally well known, served as a control. In all these patients a negative magnesium balance could be demonstrated being significantly higher (p less than 0.01) in those receiving cytostatic therapy. PMID- 2603586 TI - Zinc, magnesium and copper in serum of women given a calcium supplement. AB - Earlier investigators have demonstrated in animal studies interrelationships between mineral elements. Serum zinc, magnesium and copper were monitored over a two year period in 120 women between the ages of 40 and 55 years. One group (65 women) was supplemented with calcium, the other served as a control. We concluded that calcium supplementation at a level of 1,500 mg Ca mainly does not affect serum zinc, magnesium and copper, however, serum copper concentration is elevated in women taking medication for hypertension. PMID- 2603587 TI - [HELLP syndrome--a case report]. AB - A case of HELLP-Syndrome is reported. The age of the patient was 27 years. Diagnostic features, pattern pathophysiology and therapy are discussed. PMID- 2603589 TI - [Questions to the editors. Treatment of eccentric breast cancers]. PMID- 2603588 TI - [Stromal sarcoma of the vagina]. AB - A rare case of primary stromal sarcoma of the vagina is reported. The age of the patient was 72 years. The presenting symptom was an increase in the size of the mass. Local excision, followed by radiotherapy. The patient succumbed to their disease by metastases in pelvis and lungs 6 months after diagnosis. PMID- 2603590 TI - Electric current distribution in tissues upon electrotherapy. AB - The authors have used computer simulations to study electric current distribution in tissues upon electrotherapy. The results are shown on a computer plot and apply to various types of current. Simulations on a simplified circular structure (as a model of a limb cross section) give a better understanding of the problem and clearly demonstrate the influence of electrode position and geometry. Simulations have established the possibility of directing the current density at particular internal areas. The greatest current density occurs close to the surface of the bone in an area midway between the electrodes, and larger electrodes may make treatment more effective. These conclusions are verified in the more realistic structure of a thigh cross section and extrapolation to a length section is made. Finally, the influence of metallic implants is considered. The conclusions of this work are of great practical interest to electrotherapy, particularly electrode techniques. PMID- 2603591 TI - (Chloro-4 phenyl) thiomethylene biphosphonate in Paget's bone disease. AB - Several biphosphonates (PCT) have been used as therapeutic agents for Paget's bone disease. CIPsMBP has recently been shown to have a significant antiosteoclastic activity while defect in mineralization was only apparent at high doses. For six months, we tested this drug in 23 pagetic patients distributed in three groups. Gr 1 (n = 5) receiving 200 mg/day showed a decrease of serum alkaline phosphatase (SAP) to 42 +/- 4% (p less than 0.01) of initial value (100%) while hydroxyprolinuria/creatinuria ratio (OH/Cr) dropped to 69 +/- 8% of baseline. In 4 patients receiving 400 mg/day, SAP improved to 48 +/- 9% of initial value (p less than 0.01) and OH/Cr to 40 +/- 3% (p less than 0.01). In the last group (n = 14) receiving 200 mg/day for 3 months, and 400 mg/day thereafter up to the 6th month SAP reduced to 53 +/- 4% and OH/Cr to 62 +/- 6% of initial value (p less than 0.01). Clinical improvement was significant from the first month of treatment. No resistance (mean decrease of SAP lower than 30%) was recorded and no radiological or clinical evidence of mineralization defect appeared. The clinical and biological tolerance was excellent throughout the study. PMID- 2603592 TI - [Role of the CT scanner in imaging of the patello-femoral joint]. PMID- 2603594 TI - [The cushioning ability of various insoles]. PMID- 2603593 TI - [Congenital coxa vara]. PMID- 2603595 TI - [Isolated paralysis of the long thoracic nerve]. PMID- 2603596 TI - [Tendon disorders of the external surface of the knee]. PMID- 2603598 TI - [Puncture-lavage of calcifications of the sub-epineural tendon]. PMID- 2603597 TI - [[The effect of cisapride on the neurogenic bladder]. AB - Cisapride (Prepulsid) is a new prokinetic drug of the gastrointestinal tract. It has indirect muscarinic parasympathicomimetic effects on the neuromuscular junction of smooth muscle that we also observed on the vesical function by four of the six patients presented in this study. PMID- 2603599 TI - [Mesotherapy in abarticular rheumatism]. AB - Mesotherapy is a method of treatment in which subcutaneous infiltrations are given loco dolenti at short intervals of time. In this way a mixture of readily available drugs is administered. There are many indications for mesotherapy, although most applications are found in the field of the osteo-articular affections. As yet there is no scientific explanation for the effect of this therapy. Studies on this subject are currently being performed. PMID- 2603600 TI - Evolving European consensus on critical limb ischaemia. PMID- 2603601 TI - The value of ischaemic heart disease vital statistics since 1968. AB - Although individual cases of IHD (Ischaemic Heart Disease) are frequently misclassified, the overall reliability of IHD vital statistics in industrialized countries is better than claimed. Random classification errors produce a correct mean value, whereas systematic misclassifications produce an opposite change in one or more different causes of death, since total number of deaths is correct in the age group and countries under consideration. Therefore it is important to compare a certified cause of death to several others, including total mortality. The comparison of death rates should be done in many countries, over several years, for each sex and between sexes. Since the 8th revision (1968) the comparability between years has improved. The mean mortality rates over the available years, the slopes calculated over the years and the % change of IHD in men and in women were correlated with different causes of death in men and in women, totalling 111 comparisons. Some of these (cancer of the rectum, colon, prostate and breast, diabetes and stroke) are related with nutrition. In total 71 out of the 111 correlations were significant, 28 of which with p less than 0.001. Criteria have been defined for checking the reliability of the slopes of IHD mortality with time since 1968. The trends in IHD mortality were compared with observed changes in nutrition. These nutritional changes, especially those of saturated fat, are generally consistent with the observed rates or time trends of the diseases under consideration. In conclusion, although classification errors occur they are not of a level of magnitude that makes valid conclusions impossible. PMID- 2603602 TI - Alternating capture of the ventricle and an unusual pacing rate. AB - The recent improvements in technology of cardiac pacing are often responsible for difficult electrocardiograms at follow-up (Gladstone et al., 1987). Therefore, it seems an advantage that most modern pacemakers include diagnostic software functions to explain the pacing behaviour (event markers, intracardiac electrograms...). In this case report an electrocardiogram, showing pacing dysfunction of a physiologic pacemaker with rate response is presented. It was possible to understand what was happening without electrograms, but confirmation of our interpretation of the pacing behaviour was only possible with telemetric data. PMID- 2603603 TI - Antegrade conduction over a concealed accessory pathway after His bundle catheter ablation. AB - The existence of unidirectional retrograde preexcitation or concealed bypass fibers and their role in paroxysmal supraventricular tachycardia have been known for a long time. However, the exact anatomic and physiological nature of this retrograde limb remains unclear. We report here on a patient who had a concealed accessory pathway (AP) with circus movement tachycardia. After His bundle catheter ablation the AP had the property to conduct in the antegrade direction. The absence of antegrade conduction over the AP before ablation is likely due to its decremental properties of conduction and to repetitive retrograde concealed conduction from the normal pathway. PMID- 2603604 TI - Ketanserin and syncope. PMID- 2603605 TI - Ventricular arrhythmias and QT-prolongation during therapy with ketanserin: report of a case. AB - A patient is reported who developed a marked prolongation of QTc and life threatening ventricular arrhythmias during oral Ketanserin therapy. No other factors contributing to the QTc prolongation or to the occurrence of ventricular arrhythmias were found. The relevant literature is reviewed. PMID- 2603606 TI - Sequelae of axillary dissection vs. axillary sampling with or without irradiation for breast cancer. A randomized trial. AB - One hundred women with operable breast cancer were randomized to two equal groups. In group A the aim was to remove all fat tissue in the axilla. In group B suspectedly pathologic nodes were removed, and if no nodes were palpable the lower half of the axillary fat was excised. Irrespective of this grouping, partial mastectomy was generally performed for T1 tumour (17 in each group) and mastectomy for T2 tumour (33 in each group). Also irrespective of A and B grouping, radiotherapy including the axilla was given after partial mastectomy, and to women under 70 with T2 tumour and/or lymph-node secondaries. Arm volume and shoulder mobility were measured before and 3, 6 and 12 months after surgery. Arm oedema (greater than or equal to 10% volume increase) was found in 14 group A patients, but none in group B. Twelve of the 14 patients with arm oedema had been irradiated. Subjective sensation of arm swelling in the absence of an objectively measurable increase in arm volume was also more common after axillary dissection plus irradiation than after the other forms of treatment. Impairment of shoulder mobility was more frequent after axillary irradiation. PMID- 2603608 TI - Pre- and postischemic transcutaneous oxygen tension measurements and the determination of amputation level in ischemic limbs. AB - The value of transcutaneous pO2 (TCpO2) measurements in determining amputation levels was studied in patients with atherosclerotic lower limb ischemia. A postischemic TCpO2 response did not predict healing of the amputation stump better than measurements at rest. No minimal resting or postischemic TCpO2 was found below which healing could not occur. However high TCpO2 values probably are indicative of a good healing potential. In patients with poor skin viability, assessed clinically, the method may be of value; in some cases TCpO2 values compatible with healing may be found. Attention should be paid to the TCpO2 sensor as its characteristics may influence the measurements in patients with critical ischemia causing underestimation of tissue pO2. PMID- 2603607 TI - Serum creatine kinase-B activity in patients with chronic lower-limb ischemia and after leg amputation. AB - Serum creatine kinase-B (CK-B) activity was measured and electrocardiograms (ECG) recorded before and after operation in two groups of ten orthopedic patients. Group I underwent lower-limb amputation because of severe, chronic ischemia of the leg and group II (controls) had knee prosthesis implantation or knee ligament surgery. In group I the number of patients with CK-B activities exceeding the discrimination value (0.25 muka-tal/l) for acute myocardial infarction preoperatively and 2, 24, 48, 72 hours, and at 7 days postoperatively were, respectively, three, three, five, three, two and nil. In Group II the serum CK-B activity remained below the myocardial infarction discrimination value in all patients at all times. No ECG abnormalities indicating myocardial infarction appeared in any patient of either group. The study indicates that severe, chronic lower-limb ischemia and amputation of the leg may cause elevation of non-cardiac CK-B activity in serum that can interfere with enzymatic recognition of acute myocardial infarction. PMID- 2603609 TI - Splenic function after splenectomy for trauma. Role of autotransplantation and splenosis. AB - Follow-up of patients treated for severe trauma to the spleen, with autotransplantation (20 cases) or splenectomy (21 cases) included hepatic and splenic scintigraphy, intracutaneous skin testing with seven recall antigens and hematologic studies (red and white blood count, Howell-Jolly bodies, erythrocyte morphology, immunoglobulins, complements). In all reimplantation cases splenic tissue was scintigraphically demonstrated. After removal of the spleen due to severe traumatic ruptures the incidence of splenosis was 66%. Good clearance function in all reimplantation and splenosis cases was demonstrated by Howell Jolly bodies and erythrocyte morphology. Autotransplantation of splenic tissue is a simple and safe procedure, without serious complications. As yet, however, there is no proof that it provides adequate resistance to infections. Reimplantation, therefore, should be performed only if spleen-preserving procedures are not feasible. PMID- 2603610 TI - Aortoduodenal fistula reconstructed with autogenous tissue. Case report. AB - Aortoenteric fistula is a rare but serious complication of aortic surgery. A case of secondary aortoduodenal fistula is presented. Treatment with closure of the fistula and removal of part of the graft was successful. The circulation was restored by autogenous saphenous vein bypass grafting. PMID- 2603611 TI - Papillary adenoma of the gallbladder associated with regurgitation of pancreatic juice through abnormally shaped union. Case report. AB - In a 52-year-old woman papillary adenoma of the gallbladder was associated with regurgitation of pancreatic juice into the biliary tract via an abnormally shaped union, not a long common channel. The condition was demonstrated by endoscopic retrograde cholangiography and histologically confirmed. Extended cholecystectomy and lymph-node dissection were performed. PMID- 2603612 TI - Late sequelae of central pancreatic necrosis. Case report. AB - Three cases of complete central pancreatic atrophy following acute pancreatitis are described. The isolated pancreatic tail did not regress, but continued to secrete pancreatic juice through a chronic fistula or recurrent pseudocyst. To our knowledge this clinical entity has not previously attracted attention in the literature. PMID- 2603613 TI - A carcinoid tumor of the ileum. A case report and a brief review of the relevant literature. Case report. AB - An unusual case of carcinoid tumor of the ileum is presented where a metastatic deposit in the spine was removed 10 years before the primary lesion could be detected. The primary tumor was 3 cm in diameter with a hepatic metastasis, however, the patient was completely asymptomatic, and the lesions were only discovered accidentally. The discussion illustrates the diagnostic difficulties of small bowel carcinoids and that surgery as the only curative treatment has a role to play even in advanced stages. Understanding the pathological basis of this uncommon tumor is essential for the choice of most appropriate treatment. PMID- 2603614 TI - [Incidence of viral liver diseases in the province of Corrientes in various populations]. AB - The hepatitis incidence of A and B markers is being analyzed in 600 persons with different characteristics. Where tested 276 Sanitary Agents, 56 Convicts, 36 Hemodialyzed persons, 32 Prostitutes and 200 women in childbirth. It's found that more than 90% of the population studied had contact with VHA. Regarding VHB the incidence for the different groups (measure in anti-HBc positivity) is variable according to risk: Sanitary persons 19.20%, Convicts 12.50%, Hemodialyzed persons 86.11%, Prostitutes 53.12% and women in childbirth 2%. PMID- 2603615 TI - [Significant correlations of mortality due to stomach and colonic cancer in Rosario with other neoplastic sites]. AB - The age standardized mortality rates, by sex, for cancer all sites and some diagnostic sites were calculated in the 22 Areas of the city of Rosario during the period 1977-81. The rates of the different cancer sites, by Areas, were correlated with stomach and colon cancers, by sex, applying the Kendall's tau, a non-parametric method of correlation. While the mortality rates for cancer all sites and for stomach cancer in males were higher than in females in almost all of the Areas, for colon cancer they were almost similar. Colon cancer rates in both sexes had negative correlations with infant mortality rates, and in females had positive correlations with breast cancer, and negative correlations with cervix and uterus cancer. Stomach mortality rates had negative correlations with those of colon in both sexes, and positive correlations with total cancer and infant mortality rates. The distribution of the mortality rates of some cancer sites and their correlations suggest that some risk factors and shared in their causal chain. PMID- 2603616 TI - [Primary amyloidosis. Clinical manifestations]. AB - Amyloidosis is distinguished by store both localized or systemic, of a substance conformed for 3 fraction: 1) protein (90%), 2) Mucopolysaccharides, 3) fatty and iron, with filament ultrastructure. These filaments are thin and rigid, with beta crystallographic shape. Four pattern of amyloid are distinguished. They are derived of light chains or another immunoglobulins, aminoacids or prealbumin like substance. If all deposits are protein filaments storage, one of their trials would be increased synthesis of them. This is not sufficient and need that these precursor proteins be attrached by macrophages they are subjected to proteolysis and are enclosed extracellularly. We present a female, 55 years old. The hepatic and renal participation permit to suspect an amyloidosis who is confirmed by the presence of monoclonal gammopathy and by biopsy of tissues. PMID- 2603617 TI - [Gastroduodenal erosions and endoscopy]. PMID- 2603618 TI - [Primary lymphoma of the small intestine and malabsorption]. PMID- 2603619 TI - [Clinical and laboratory correlation of severe esophagitis compared to mild or moderate esophagitis]. AB - Between 1976-1987, 408 patients were studied for Reflux Esophagitis. Clinical, endoscopic, manometric characteristic were analyzed, and scintigraphic studies for gastroesophageal and duodenogastric reflux were done. Esophagitis was classified according endoscopic findings in Esophagitis grade I (non confluent erosion), grade II (confluent erosions), grade III ("uncomplicated Barrett syndrome") and grade IV (esophageal ulcer or stricture ("complicated Barrett syndrome"). Fifty six (56) patients with mild (grade I), 52 with moderate (grade II) and 146 patients with severe esophagitis (56 grade III, and 90 grade IV) were included in this protocol. No significative differences were found in clinical feature except dysphagia and bleeding, symptoms more frequent in severe esophagitis than mild or moderate grades. Lower esophageal sphincter pressure was similar in both groups of patients, but the frequency of motor disorders was significative higher in severe esophagitis. Scintigraphic gastroesophageal reflux was positive in all patients and no differences in gastric emptying and duodenogastric reflux were detected. In conclusion, the differences in subjective and objective analysis between different grade of esophagitis suggest to employ different models of management. PMID- 2603620 TI - Inappropriate use of central venous catheters results in one in ten complications. PMID- 2603621 TI - Nurse anesthetists and podiatrists. PMID- 2603622 TI - CRNA fee schedule legislation. PMID- 2603624 TI - Anesthesia machine systems. PMID- 2603623 TI - AANA journal course: new technologies in anesthesia: update for nurse anesthetists--intraoperative blood salvage. AB - The transfusion of blood and blood products is often a lifesaving measure in a variety of medical and surgical conditions. The benefits of transfusion are increasingly contrasted with associated risks. Today, various alternatives exist that attempt to minimize or eliminate the known transmission of infection or reactions attributed to transfusion. The intraoperative salvage and reinfusion of red blood cells is one of the alternatives and is the focus of this lesson. PMID- 2603625 TI - Monitoring ventilation. PMID- 2603626 TI - Choosing a career in psychiatric-mental nursing: do more clinical placements in this area for undergraduate student nurses make a difference? (Part two). PMID- 2603627 TI - Dr. Sara T. Fry. Interview by Eve Henderson. PMID- 2603628 TI - A different path to the same goal. PMID- 2603629 TI - Nurses and post-secondary education. Another tax deferral--the R.E.S.P.? PMID- 2603630 TI - Scanning, transmission and immunoelectron microscopical studies of the tonsil like lymphoid organ of normal and horseradish-peroxidase-injected laboratory suncuses. AB - Fine structures of normal and horseradish peroxidase (HRP)-stimulated tonsil-like lymphoid organs of the laboratory suncus (Suncus murinus) were examined by scanning, transmission and immunoelectron microscopies. The normal organs appear as a pair of small oval protrusions at the upper lateral sites of the fauces, and consist of a single lymph nodule with a germinal center and a crypt-like epithelium with prominent lymphoid cell infiltration. Postcapillary venules (PCV) and efferent lymphatics are associated within the marginal region of the nodule and separated from the neighboring pharyngeal tissues. Numerous lympho-plasma cells, interdigitating cells and reticulum cells occurred within the lymphoid parenchyma, as well as in the intraepithelial infiltrating cell populations. In the HRP-stimulated animals, the anti-HRP antibodies producing lympho-plasma cells were often seen in the parenchyma and epithelia; however, similar HRP-antibody positive lymphocytes were rarely detected in the PCV lumina. In addition, some HRP antibody bearing interdigitating cells were also identified in the same parenchyma. These data indicate that the suncus' tonsil-like organs have a positive immune function to oral antigens, together with the suncus' systemic immune system and it is hypothetically presumed that the organ may correspond to a homologous organ of the human palatine tonsil in comparative anatomy. PMID- 2603631 TI - Morphometric data on the lymph capillaries of the ventricles of the rabbit heart. AB - A morphometric analysis was done on the lymph capillaries of both left and right ventricles from the rabbit heart. The measurements were made on the lymphatics identified in the subepicardium, myocardium and subendocardium of the ventricular walls. Quantitative evaluations were carried out on light and electron microscopic sections by a computerized image analysis system. The following parameters were selected and measured: (1) the diameter (of area-equivalent circle) of lymph capillaries, (2) the diameter of the uncoated micropinocytotic vesicles (located on the abluminal and adluminal side and in the cytoplasm of the endothelial cell) and the area occupied by the vesicles per unit area of cytoplasm. Differences in the size of the lymph capillaries were found in the three layers (subepicardium, myocardium and subendocardium) of the ventricular walls. The largest vessels were present in the subepicardium both in the left ventricle and in the right one. No significant variations were found in the lymphatics of corresponding regions on both ventricles. Little variations on the mean diameter of the uncoated micropinocytotic vesicles are present in the three regions of the endothelial wall. In the left ventricle only, the subendocardial vesicles are significantly larger than the subepicardial and the myocardial ones (p less than 0.05). The areal density occupied by vesicular system in the three layers of the ventricular wall showed significant differences in both ventricles (p less than 0.05). The vesicles present in the subepicardial vessels occupied the smallest areal density. No significant variations existed in the vesicular areal density between the two ventricles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2603632 TI - Development of the various glial cell types in the cerebral cortex of postnatal rats. AB - The present quantitative study in the postnatal rats showed the rapid growth of the various glial cell types in the cerebral cortex. Among them, the increase of microglia was most dramatic. The increase was about 15 times, covering a period of 15 days extending from 5 days of age to 20 days. The majority of the microglia observed were in the outer third of the cortex. During the same period, the number of oligodendrocytes and astrocytes also showed a steady but moderate increase. The increase of oligodendrocytes was most significant between 5 and 10 days. Their density was greater in the inner third of the cortex. Astrocytes were distributed uniformly throughout. Examination of the cerebral cortex in 1- to 3 day-old rats by electron microscopy showed sporadic ameboid microglia cells and glioblasts. The possibility that they served as the precursor cells of microglia and macroglia (astrocytes and oligodendrocytes), respectively, was considered. PMID- 2603633 TI - Milky spots in the human greater omentum. Macroscopic and histological identification. AB - Macroscopic and histological investigations were made from surgical specimens demonstrating milky spots in the human greater omentum from subjects of various ages. The milky spots in the human greater omentum appear as tiny, cotton-wool like masses to the naked eye. Histologically, the milky spots consisted mainly of many macrophages with diffuse cytoplasmic esterase reaction products and esterase negative B lymphocytes surrounding the vascular networks. Macrophages phagocytosed many carbon particles which were introduced as a carbon suspension during the operation. The vascular networks were blood capillary convolutions with a glomerular shape. Silver impregnation showed the delicate networks of reticular fibers which constitute the framework of the organ. The number of milky spots was highest in infancy and gradually decreased with age. PMID- 2603634 TI - Anterior spinal arteries. Origin and distribution in man. AB - This study was designed to extend our present knowledge of the origin and distribution of anterior spinal arteries and was carried our using 31 human cadavers with arterial injections of natural latex. The conclusions reached are that there are always one or two anterior spinal arteries (right or left), which proceed from the intracranial segment of the vertebral arteries. These arteries have a descending course, with distribution into the ventral face of the medulla oblongata and the first cervical segments of the medulla spinalis. In cases where there are two anterior spinal arteries, they anastomose with each other to form the common, unpaired and median anterior spinal artery. The different observed locations of the origins of anterior spinal arteries may be systematised into three types. Each of these types has differential characteristics: bilateral origin (type I; 77.4%), unilateral origin (type II; 9.7%) and origin in an intervertebral transversal anastomosis (type III; 12.9%). We do however subdivide the bilateral origin group, according to the calibre of the arteries, into the subtypes 'balanced' (type Ia; 22.6%), 'right dominated' (type Ib; 32.2%) and 'left dominated' (type Ic; 22.6%). The collaterals of the anterior spinal arteries which distribute into the ventral face of the medulla oblongata are described. PMID- 2603635 TI - Quantitative study of circadian variations in mast cell number in different regions of the mouse. AB - The tongue, pinna and dorsal skin of adult male C-1 mice were removed at 03.00, 06.00, 09.00, 12.00, 15.00, 18.00, 21.00 and 24.00 h, fixed in basic lead acetate and stained with Alcian blue-safranin or 0.5% toluidine blue. The mast cell numbers of these regions were counted and analyzed statistically by analysis of variance. It was found that there were circadian variations in the mast cell number in the tongue, pinna and dorsal skin. The difference between the minimum and maximum of circadian variation in mast cell number in all three regions was highly significant (p less than 0.01). Furthermore, the time points of the maximum and minimum of mast cell number varied between the different regions. The time point of the minimum in the tongue and pinna was at 06.00 h, whereas it was at 09.00 h in the dorsal skin. The time point of the maximum in the tongue and dorsal skin was at 21.00 h, but in the pinna it was at 18.00 h. PMID- 2603636 TI - Histochemistry of glycoconjugates in the skin of the bovine muzzle, with special reference to glandular structures. AB - The distribution of glycoconjugates in the muzzle of young adult Holstein cows has been studied by means of selected light-microscopic histochemical methods, including lectin histochemistry. In the skin layers, strong reactions were confined to intercellular substances in between the cells of the vital epidermis, exhibiting neutral glycoconjugates mainly with alpha-D-galactosyl and N-acetyl-D galactosaminyl residues. In the nasolabial glands, distinctly positive staining for neutral glycoproteins with various saccharide residues (alpha-D-galactose, alpha-N-acetylgalactosamine, D-galactose-beta(1----3)D-N-acetylgalactosamine, beta-D-galactose), and for smaller amounts of acidic glycoconjugates, was found in the secretory cells and the luminal secretion. The cells of the excretory duct system showed weak to moderate reactions (alpha-D-galactose, beta-D-galactose), only the collecting ducts reacted positively for acidic glycoproteins with sialyl residues. The results obtained are discussed in view of muzzle function, with special reference to the salivary nature of the secretion of bovine nasolabial glands. PMID- 2603637 TI - Upper jaw in human cyclopia. AB - In human cyclopia the upper jaw forms a solid bony mass between the median orbit and the oral cavity. The skeletal elements forming the upper jaw have been studied in serial sections through the median third of the head in 3 perinatal human specimens presenting with a median orbit and proboscis. One head was sectioned in the sagittal plane and 2 in the coronal plane. The upper jaw has also been studied in a dried cyclops skull and in a desiccated cyclops head in which the roof of the orbit had been removed. The data obtained demonstrate the particular contributions made by the lacrimal bones, the maxillae and the palatine bones to the upper jaw in human cyclopia. The effects of the absence of the frontonasal process contribution and of the absence of the nasal cavity on the upper jaw in cyclopia are considered. PMID- 2603638 TI - Effects of isoproterenol treatment on the parathyroid glands in golden hamsters of different ages, with special reference to the frequency of lipid droplets. AB - The frequency of lipid droplets in the parathyroid glands of young, adult and senile golden hamsters after treatment with isoproterenol was investigated. In the parathyroid glands of the young and senile animals the number of lipid droplets increased gradually by 1 h, and thereafter it remained almost unchanged at 3 h after administration. In the glands of adult animals it increased, at first rapidly and then gradually, by 3 h after administration. It is considered that in the parathyroid glands of the golden hamsters stimulated by isoproterenol there is a relationship between the number of lipid droplets and aging. PMID- 2603639 TI - [The hydrodynamic components in joints: proof of a membrane-cistern system within the calcified zone of the femur head cartilage]. AB - The theoretical postulate of a hydrodynamic system for the transmission of forces at the hip joint led to the discovery of a two-membrane system. Within the calcified cartilaginous zone of the femoral head there exists a system of small spaces and cisterns which can only be understood in the postulated sense as an overall acting hydrodynamic system. A correlation between the destruction of the calcified zone, i.e. the hydrodynamic system, and arthrosis is indicated. Ongoing studies and deliberations will help to discover the true model of the transmission of forces and impulses and to solve the problems of treating arthrosis. PMID- 2603640 TI - Two-membrane system in the caput femoris and the distal femoral condyles. PMID- 2603641 TI - Histamine production by Haemophilus. AB - Eight Haemophilus influenzae and four Haemophilus parainfluenzae strains, all freshly isolated from patients, were examined for histamine production. Histamine was produced by all the H. influenzae (0.06 microgram-2.6 micrograms/100 ml) and by two of the H. parainfluenzae strains (46.5-47.9 micrograms/100 ml). It is concluded that histamine which plays an important role in the pathogenesis of chronic aspecific respiratory diseases, may derive not only from degranulation of mast cells, but also produced by Haemophilus. PMID- 2603642 TI - Toxic shock syndrome toxin-1 (TSST-1) production in staphylococcal infections and serological implications with patients and healthy controls. AB - TSST-1 production occurred in 4.6% among Staphylococcus aureus strains isolated from divergent clinical sources in South-West Hungary. Patients suffering from staphylococcal infections, whether or not harbouring TSST-1 positive strains, exhibited low anti TSST-1 titres in their acute phase sera compared to the healthy control population. A S. aureus strain isolated from toxic shock syndrome (TSS) was a high collagen binder and a low fibronectin and fibrinogen binder suggesting the role of connective tissue adhesion in colonization and low invasive property of TSS strains. PMID- 2603643 TI - Comparison of the effects of peritoneal and spleen cells of syngeneic or allogeneic origin on the take of transplantable murine tumours. AB - We compared the effects of various potential effector cells of syngeneic or allogeneic origin on the take of a spontaneous adenocarcinoma (SP4) and Lewis lung (LL) carcinoma. As reported earlier, syngeneic resident (non-activated) peritoneal cells (PC) did not inhibit the take of these tumours. On the contrary, transfer of resident PC from allogeneic donors suppressed the tumour take. Syngeneic and allogeneic PC activated by poly I:C or by a combination of indomethacin, poly I:C and Syncumar ("combined treatment") inhibited the tumour take to a similar extent. Syngeneic spleen cells (from untreated mice or from donors underwent "combined treatment") did not inhibit the take of Lewis lung tumour. Transfer of activated allogeneic spleen cells resulted in a stronger inhibition of tumour take than the transfer of resident allogeneic spleen cells. PMID- 2603644 TI - Plasma fibronectin concentration in germfree and conventional mice of various age. AB - Lower plasma fibronectin (FN) levels were detected in C3H germfree (Gf) mice as compared to conventional (Cv) ones. FN levels increased with aging both in Gf and Cv mice. Stimulation of the immune system with live Newcastle disease virus (NDV) vaccine increased the FN levels in young germfree mice, but had no effect in conventionals. PMID- 2603645 TI - Characterization of activated peritoneal cells inhibiting the take of transplantable murine tumours. AB - We studied the properties of activated peritoneal cells (PC) inhibiting the take of SP4 spontaneous adenocarcinoma and Lewis lung carcinoma in syngeneic mice. Treatment of the poly I:C activated PC from Balb/c mice suppressing the take of SP4 tumour with anti-asialo GM1 antibody and complement before transfer did not affect their tumour-inhibitory potential. PC from Balb/c nude mice treated with poly I:C also inhibited the take of SP4 tumour. Spleen cells from untreated or poly I:C treated Balb/c and Balb/c nude mice, however, did not inhibit the take of SP4 adenocarcinoma. Treatment of peritoneal cells activated by a combination of poly I:C, indomethacin and Syncumar (referred to as "combined treatment") with anti-asialo GM1 antibody and complement could not, or could only partly abolish their tumour-inhibitory potential. The cells mediating the suppression of the take of Lewis lung tumour proved to be Thy-1,2+/-, Lyt-1-, Lyt 2.2- cells. We conclude that the activated peritoneal cells inhibiting the take of SP4 adenocarcinoma and Lewis lung tumour are different from NK cells, NC cells and LAK cells and represent a distinct antitumoural effector cell population. PMID- 2603646 TI - Molecular cloning and physical mapping of the DNA of human adenovirus type 35. AB - The prototype strain of the human adenovirus type 35 (AV35) was examined. BamHI, EcoRI, HindIII, KpnI, PstI, and SalI restriction endonucleases were used for the mapping of DNA fragments. Three original maps were constructed, and previously published maps were somewhat modified. A PstI-specific fragment library was also prepared and characterized using the pBR322/E. coli system. Some of the recombinants seem to be applicable for rapid DNA diagnostics, and for the comparative mapping of type- and subgroup-specific DNA sequences. The comparative presentation of physical maps of subgroup B human adenoviruses might improve the efficiency of genotyping of adenoviruses using restriction endonucleases. PMID- 2603647 TI - Risk involvement with Staphylococcus aureus exotoxins among pyogenic skin infections with special reference to toxic shock syndrome. AB - The sera of three patients involved in a non-menstrual toxic shock syndrome outbreak showed TSST-1 at a concentration above 40 ng/ml and no antibodies of IgG class against the toxin. A Staphylococcus aureus strain producing TSST-1 was isolated from one of the patients. S. aureus strains showing similar phage type and biotype patterns were isolated from 473 out of 876 close contacts with the patients involved in this outbreak. This carriage and spread was traced to pyogenic skin infections (mainly "folliculitis") among this population. Serological studies indicated that during the early phase of the outbreak anti TSST-1 titres were low then rose gradually. In a further related study the frequency of enterotoxin production was found 48.5% among staphylococci isolated from pyogenic skin infections. Our data indicated that pyogenic skin infections are potential source for toxic shock syndrome. PMID- 2603648 TI - Differentiated treatment of Colles' fracture. PMID- 2603649 TI - Oculomotor problems after cervical spine injury. AB - Oculomotor function was investigated in 39 patients with a previous soft-tissue injury of the cervical spine. The velocity, the accuracy, and the pattern of the eye movements were disturbed in 20 patients with chronic and disabling symptoms. Oculomotor function in the 19 asymptomatic patients did not differ from a control group. The oculomotor function seems to be impaired, possibly by brain stem lesions, in patients with chronic symptoms of whiplash injury of the cervical spine. PMID- 2603650 TI - Synovectomy of the rheumatoid knee does not prevent deterioration. 7-year follow up of 83 cases. AB - Eighty-three knees in 65 patients were studied retrospectively 7 (3-11) years after synovectomy for rheumatoid arthritis. Half of all the knees had an osteotomy or prosthesis operation after a median interval of 4 years. Early synovectomy had been performed in 67 knees; half of these had a satisfactory result. Most of the late synovectomies were unsatisfactory. Our results support the opinion that deterioration of the rheumatoid knee cannot be prevented by early synovectomy. Late synovectomy is discouraged. PMID- 2603651 TI - Function after tibial osteotomy for medial gonarthrosis below aged 50 years. AB - Twenty-seven patients (28 knees), with a median age of 42 (27-50) years treated with a high tibial osteotomy for early medial gonarthrosis (Ahlback's Stage I) were examined after 11 (7-18) years. Twenty-four were men; 18 knees had had previous meniscus and ligament lesions. At follow-up, 22 knees were satisfactory and 9 patients managed high-activity sports or heavy work. In 25/28 knees, the arthrotic process had not progressed radiographically. PMID- 2603652 TI - Loosening of the Charnley hip. Radiographic analysis of 102 revisions. AB - This retrospective study was based on 102 Charnley hip arthroplasties that underwent a revision operation. Radiographs of hips with loose prosthetic components were compared with those with firm components. Migration and tilting of the socket and subsidence and varus shift of the stem were associated with loosening. PMID- 2603654 TI - Osteochondritis dissecans in Perthes' disease. Report of 7 cases. AB - We report 7 cases of osteochondritis dissecans following Perthes' disease in 363 hips, i.e., an incidence of 2 percent. Six of the 7 cases belonged to Salter group B (Catterall Groups III-IV), indicating a higher incidence in hips with a worse prognosis. Six cases were asymptomatic and did not require treatment; in 3 of these, there was spontaneous radiographic healing of the lesion. PMID- 2603653 TI - Plain radiographs inadequate for evaluation of the cement-bone interface in the hip prosthesis. A cadaver study of femoral stems. AB - To determine whether plain radiographs accurately represent the true cement-bone interlock, a comparison was made between radiographs and macroscopic morphology on cross sections of 11 human femora into which a cemented endoprosthesis had been inserted. Four femora had been retrieved postmortem from patients with a hip arthroplasty, and seven cadaver femora were cemented under varying conditions. All the femora were radiographed and then cut for macroscopic inspection of the cement-bone interface with respect to gross interposition, depth of cement penetration, integrity of the bone bed, and lamellation of the cement. PMID- 2603655 TI - Replacement of the anterior cruciate ligament. A comparison of autografts and allografts in dogs. AB - To compare the efficacy of allograft versus autograft replacement of the anterior cruciate ligament, 15 dogs had the ligament cut and replaced 1 month later: 11 dogs received a frozen bone-ligament-bone allograft cruciate ligament, while 4 dogs received a standard autogenous replacement with iliotibial band. Three of 11 allograft dogs developed postoperative infections and were removed from the study; and two of the remaining eight allograft ligaments were absent at autopsy. All the autograft ligaments were present. From serial clinical and radiographic examinations, there were no differences observed in the two groups. Autopsy studies at 4 months, however, showed an increased inflammatory, pannus-like reaction about the origins and insertions of the six allograft ligaments as compared with the four autografts. The ligament hydroxyproline uptake was lower in the allograft group, averaging 60 percent of the contralateral unoperated on control versus equal to the control in the autograft group. The tensile strength of the allografts reached only 17 percent of the control value versus 41 percent for the autografts. Lymphocytotoxicity testing at 1 month revealed a donor specific antibody response in 4 of 8 allograft dogs; however, no histologic evidence of immune response was observed in the ligaments. The synovial fluid leukocyte count was elevated in the allograft group at 4 months. The increased synovial leukocyte counts and joint cartilage erosion, the decreased strength and metabolic activity of the grafts, and the evidence of an immune response in the allograft dogs do not support implantation of cadaver cruciate ligaments clinically at this time. PMID- 2603657 TI - Glove perforation in elective orthopedic surgery. AB - A survey of glove perforation in 16 orthopedic surgeons during a 6-month period was carried out. During this time, the surgeons performed 304 elective operations. In 1,398 pairs of gloves tested, evidence of perforation was found in 26 percent. PMID- 2603656 TI - Primary suture of the anterior cruciate ligament. A 6-year follow-up of 74 cases. AB - Seventy-four consecutive patients were reviewed 6 (3-9) years after primary suture according to Palmer of a fresh rupture of the anterior cruciate ligament. Three fourths had excellent or good function as evaluated by the Lysholm score. The pivot shift test was trace-positive in one fifth and 2+ or 3+ in one quarter, and the Lachman test was 2+ or higher in one third. Tibial anterior instability was present in 23 knees. Radiographically, 15 knees had signs of arthrosis, 4 of which severe. Our 0.25 failure rate suggests that other procedures should be considered in the treatment of acute rupture of the anterior cruciate ligament. PMID- 2603658 TI - Hip fractures in northern Sweden 1973-1984. A comparison of rural and urban populations. AB - The hip-fracture incidence in persons aged 50 years and older in the two northernmost counties of Sweden was studied during three periods between 1973 and 1984. The mean age rose from 75 to 78 years, and the annual number of fractures increased from 511 to 754. Half of this increase could be attributed to demographic aging. For persons 80 years and older, the fracture incidence in 1983/84 was higher (P less than 0.01) than the fracture incidence in 1973/74. The women/men ratio was approximately 2:1 during the survey, while the ratio cervical/trochanteric fracture type changed from 1.7:1 to 1.8:1. The crude fracture incidence rate rose from 4.4 to 5.8 fractures per 1,000 women 50 years and older; the corresponding figures for men were 2.3 and 3.4. Comparison of a rural mountain population with an urban population revealed a lower age-adjusted hip-fracture incidence rate in the rural area during the final part of the study (P less than 0.001). In the rural population, there was no change in age-specific incidence during the survey, while in the urban area the age-specific incidence in person 75 years and older was higher in 1983/84 compared with 1973/74. PMID- 2603659 TI - Function after hook-pin fixation of femoral neck fractures. Prospective 2-year follow-up of 191 cases. AB - Totally, 191 consecutive patients with femoral neck fractures during 1984 and 1985 had internal fixation with hook-pins and were prospectively investigated. Within 2 years, 62 patients had died and 47 had developed healing complications, 30 of whom had been treated with total hip replacement. Thus, 82 healed without complication. Forty-one of 47 patients without other handicaps affecting their walking ability considered their gait as good as it was preoperatively; 45 used no walking aids or a cane. Nine of 35 patients with a nonfracture-related disease affecting their walking ability managed to walk with or without a cane; 13 considered their walking ability unaltered compared with their prefracture state. Three of 82 patients complained of pain on walking and 2 of pain at rest. All but 1 could flex their hip 90 degrees or more. We believe that the function after internal fixation of cervical hip fracture with uncomplicated healing is superior to that achieved by primary hip replacement; primary replacement is recommended only in rheumatoid patients with displaced fractures. PMID- 2603660 TI - Repair of trabecular fatigue fractures. Cadaver studies of the upper femur. AB - The healing process and the distribution of trabecular fatigue fractures were studied on upper femora obtained at autopsy. Macroscopically, two main types of trabecular fatigue fractures were found on the basis of callus formation that in histologic sections were composed of woven and lamellar bone. A third type characterized by its vestigial callus was found only in histologic sections. Fatigue fractures were more numerous in regions of the femoral head submitted mainly to compressive rather than tensile stress. Trabeculae submitted to compressive stress had a majority of the type of fatigue fractures with an exuberant thorny callus composed of woven bone (most of them located subjacent to the subchondral bone plate), whereas trabeculae submitted mainly to tension or to minimal stress, as in Ward's triangle, had a majority of fatigue fractures with a small, smooth-surfaced callus composed of lamellar bone. PMID- 2603661 TI - Four cases of purulent arthritis of the shoulder secondary to hematogenous osteomyelitis. AB - In 4 cases of acute hematogenous osteomyelitis, the purulent process had penetrated the cortical bone to or lateral to the groove of the long biceps tendon. In 3 of the cases the process had spread along the tendon to the shoulder joint. In 1 case the periosteum was still intact, and the shoulder joint was not involved. The osteomyelitic focus should be reamed out until normal cancellous bone is reached. Suction irrigation drainage of the osseous cavity is recommended instead of the placement of gentamicin beads. PMID- 2603662 TI - Intramuscular pressures during exercise. Comparison of measurements with and without infusion. AB - Our objective was to compare two techniques for measuring intramuscular pressures during dynamic exercise. In 20 volunteers muscle contraction and relaxation pressures were recorded with a noninfusion method (slit catheter) and with a microcapillary infusion method (Myopress catheter). Relaxation pressures measured by noninfusion were higher than those measured by infusion. The dynamic properties of the infusion method were higher as compared with the noninfusion method. The dynamic properties of the noninfusion method increased when microcapillary infusion was connected. This resulted in a lower recording of the muscle-relaxation pressure than without infusion. We concluded that the microcapillary infusion technique and the design of the tip of the Myopress catheter are better suited for pressure recordings during exercise. PMID- 2603663 TI - Ankle fractures treated with a stabilizing shoe. AB - Twenty-four patients with a Lauge-Hansen Stage II supination-eversion fracture of the lateral malleolus were treated with a stabilizing shoe, which prevents supination and eversion of the foot, but allows a tibiotalar motion. In 23 patients the result was excellent, without secondary dislocation during healing. We therefore conclude that this fracture type can be treated functionally. PMID- 2603664 TI - Local application of growth-factor IGF-1 to healing bone. Experiments with a titanium chamber in rabbits. AB - In order to study the effects of bone healing, insulin-like growth factor 1 (IGF 1) was continuously applied with a minipump to a healing bone callus located inside a titanium chamber in a rabbit tibia. After 2 weeks, 99mTc-MDP uptake and calcium content were measured. IGF-1 decreased 99mTc-MDP uptake, and thus the mineral turnover rate, but the amount of bone mineral was unchanged. Probably the normal endogenous production of IGF-1 is already optimal for healing in this model. PMID- 2603665 TI - Dicloxacillin concentrations in amputation. AB - We treated 18 patients undergoing major lower limb amputation due to ischemia by intravenous administration of 1 g dicloxacillin either 0, 3, or 6 hours before surgery followed by a similar dose 8 hours after the first dose. The administration immediately before the operation resulted in the highest peroperative antibiotic concentrations in the muscular and subcutaneous tissue at the amputation level, exceeding the MIC value of Staphylococcus aureus. Similarly, the concentrations in drain fluid were highest in these patients. The median drain secretion later than 12 hours after surgery amounted to only 5 mL, and at that time the concentration of dicloxacillin was less than the MIC of Staphylococcus aureus in all the samples. PMID- 2603666 TI - Snapping knee from biceps femoris tendon. A case report. AB - Painful snapping of the knee was caused by the long tendon of the biceps femoris muscle sliding over the fibular head to an abnormal insertion on the tibia. Removal of the fibular head gave immediate relief. PMID- 2603667 TI - A case of acetabular fracture with hip tamponade. Relief from aspiration of hemarthrosis. PMID- 2603668 TI - Quantitative computed tomography. PMID- 2603669 TI - [Double interlocking elastic nailing for intertrochanteric fractures and various diaphyseal indications]. AB - Double interlocking elastic pinning performed through a lateral and medial approach was designed to control the lateral rotation, as well as sinking of the nails. Locking both nails with a threaded pin and two bolts limits the secondary depression of the fracture by the S-shaped lateral nail. The secondary depression of the fracture was less than 1 cm in 91% of our cases. No surgical revision was necessary for sinking nails. The control of the lateral rotation was excellent in 91% and the internal rotation was less than 10 degrees. Protrusion of the nails into the joint occurred in 4 of our first cases and could be eliminated by avoiding the superior lateral sector of the femoral head. Results, taking into account the function, shortening and lateral rotation are good in 87.5% of our cases. After plate and intramedullary rupture of the screw, in repeated fractures, this technique may be used without excising the screw fragments. Proximal and distal shaft fractures of the femur are also indications in elderly patients when monopodal rehabilitation is impossible. PMID- 2603670 TI - Achilles tendon rupture. An 8-year follow up. AB - Achilles tendon rupture is a common condition for which several short-term studies have been published. This paper describes an investigation of the long term disability as well as persistent complications and complaints arising from Achilles tendon rupture. PMID- 2603671 TI - [Radiology of patellar instability: contribution of the lateral radiography and the 30-degree axial view with external rotation]. AB - Patellar instability is often missed by conventional axial views because transient subluxation of the patella essentially occurs during the first degrees of knee flexion (0 to 30 degrees), a position in which bilateral routine axial views are impossible to obtain. However, simple radiographic methods enable detection of both patellar instability and the often associated trochlear depth insufficiency. Every lateral radiograph of the knee depicts the depth of the proximal trochlear groove which is superior to 5 mm in a normal population. Upper trochlear depth insufficiency is frequently observed in the case of major patellar instability. Lateral views of the knee recorded during the first degrees of flexion (0 degrees-15 degrees) enable detection of patellar maltracking through the patellar tilt always associated with significant subluxation of the patella. Patellar maltracking may be studied dynamically by lateral fluoroscopy during progressive flexion of the knee. Unilateral 30 degrees axial radiographs with forced lateral rotation of the leg are definitely superior to conventional axial views in detecting transient patellar subluxation. These simple radiographic modalities should replace computed tomography in the search for patellar instability. PMID- 2603673 TI - [Comparative study of a series of normal knees and a series of knees with patellar instability]. AB - In studying the long-term follow-up of 39 cases of patellofemoral instability operated in our department for recurrent dislocation, we also analyzed their morphological appearance on X-ray. We compared the data given by Maldague and Malghem, Dejour and Walch for the pathological conditions of our cases with the same number of normal knees. This comparative analysis showed that measuring the bulging of the upper part of the trochlea and the depth of its groove on a lateral view is a reliable method to evaluate patellar instability. The classical axial view gives less useful information to quantify the instability. However, this axial view shows a particular aspect in the cases of severe instability: the fulcrum of the trochlea is displaced inwards while the inner trochlear facet is smaller or even absent. This precise radiological examination and the complete clinical examination with an analysis of the "morphotype" (Lerat) are necessary in the screening, diagnosis and treatment of severe patellofemoral instability. PMID- 2603672 TI - CT arthrography and MRI of the patella. AB - The importance of CT scanning in the diagnosis of patello-femoral disorders is reviewed and illustrated. CT double-contrast technique is compared to Magnetic Resonance Imaging (MRI) using both clinical examples and a cadaver study. The authors demonstrate the superiority of MRI to CT in detecting retropatellar cartilage lesions. PMID- 2603674 TI - [Morphological types of the lower limbs in femoro-patellar disequilibrium. Analysis in 3 planes]. AB - The authors describe the relationship between the variations in the morphology of the lower limbs in case, torsional variances in femur and tibia, genu vara and genu valga with the instability of the patella. PMID- 2603675 TI - [Morphology of the tibial tuberosity]. AB - The influence of anterior projection of the tibial tuberosity in the pathogenesis of anterior knee pain syndromes has been given relatively little attention. This point has been investigated by performing a morphological study of 77 knee-joints with a standard radiological method. The knees fell into two groups: one of them included typical patellar syndromes, the other group included knees presenting with some other conditions, mostly meniscal. A subjective evaluation of the shape of the tuberosity was made and correlated with clinical status. An objective rating was attempted by measuring the anterior projection of the tuberosity, in order to eliminate the influence of skeletal size, it was expressed as a ratio between two values. Subjective evaluation of the shapes of the tuberosities was found unreliable. The individual values for the calculated index of anterior projection were found to be scattered for every morphological type. It appeared difficult to conclude that there is a definite proven relationship between hypoplasia of the tuberosity and overloading of the femoro-patellar joint. Evaluation of the anterior projection of the tuberosity should take into account the position of the tuberosity in the coronal plane. PMID- 2603676 TI - [Recurrent dislocation of the patella]. AB - The author describes the origin and the clinical signs of the disease. PMID- 2603677 TI - [Radiology in femoro-patellar pathology]. AB - For the evaluation of the femoro-patellar joint, the authors use a pure lateral view with 30 degrees flexion without weightbearing- an axial view of the patella with 30 degrees flexion- with neutral rotation- and the same view with external rotation of the foot. With these 3 X-Rays, a precise diagnosis is made possible. PMID- 2603678 TI - Arthroscopy in the diagnosis of occult dislocation of the patella. AB - The authors investigated the incidence of acute patellar dislocation by clinical and radiologic examination and by arthroscopy. Acute patellar dislocation represented 2.44% of all knee injuries in their series, and only 25% of the former were evident at the initial examination. PMID- 2603679 TI - [Method of measuring the height of the patella]. AB - The author describes a technique for evaluation of the height of the patella: it compares the distance between the lower border of the articular surface of the patella and the antero-superior border of the tibia with the length of the patellar articular cartilage. PMID- 2603680 TI - Patella alta in patellofemoral instability. AB - In a retrospective study of 90 realignment procedures for patellar instability, a high percentage of patella alta was diagnosed based upon the preoperative radiographs: 53% or 48 knees. The LP-LT index, described by Insall and Salvati, averaged 0.80 for this group of patients. Post-operative measurements of this index showed a definite correction of the craniocaudal position of the patella, with a mean increase of 0.10 (0.80 to 0.90). In evaluating the severity of the eliciting trauma, it is suggested that the alta position makes the patella more prone to instability: only 14.5% of the alta knees (n = 48) sustained a significant trauma versus 28.5% in the non-alta population (n = 42). The altaposition, however, had no influence on the final outcome, (at a mean follow up time of 57 months), after a latero-medial realignment procedure, using a proximal or a combined proximal and distal procedure. PMID- 2603681 TI - [Results of surgical treatment of patellar disequilibrium. Apropos of 311 cases]. AB - Three hundred eleven operations for patellar instability were reviewed after 2 to 10 years. Best results were obtained with surgical procedures on the quadriceps, especially with plasty of the vastus medialis and occasional transposition of the tibial tuberosity. If the procedure was limited to the patellar cartilage or the tibial tuberosity only, the results were not as good. Good results were achieved in 84 per cent of 269 patients: 14 per cent were satisfactory and 2 per cent were failures. PMID- 2603682 TI - [Initial dislocation of the patella; which treatment?]. AB - Twenty patients, victims of a first luxation of the patella, were the object of a retrospective study. They were all subjected to arthroscopic examination during which, in 7 of the patients, the liquid injected under pressure massively escaped into the subcutaneous layer of the medial side of the knee. The patients were divided into 2 groups according to the integrity of the capsule of their knees. Group I consisted of 7 patients, group II of 13 patients. The treatments, the majority of which were conservative, were quite varied, but the post-traumatic functional recuperation was much slower and more variable for the group I patients. These patients presented more significant tissue lesions which certainly contributed to the functional prognosis of the traumatized joint. Seventy two percent of the patients, equally distributed between the 2 groups, presented trochleo-patellar dysplasia. With the exception of age, different clinical parameters (sex, circumstances of the accident, clinical examination) and radiological criteria (external displacement of the patella, detached bony fragment at the interior border of the patella, value of the patellar and trochlear angles, patella alta) did not permit a distinction between the two groups. Because of our results and those in the existing literature we recommend arthroscopy, which is the only examination capable of establishing a complete picture of the lesions and which, in addition, permits rising of the joint and sometimes allows extraction of free osteo-cartilaginous fragments. The younger patients may then benefit from immediate functional reeducation. For older patients, where the tissue lesions are more important, conservative treatment is associated with a slower and sometimes variable functional recuperation. It remains to be determined, whether surgical treatment, adapted to each case, would permit us to obtain better results more rapidly. PMID- 2603683 TI - [Transposition of the tibial tuberosity in recurrent dislocations and painful femoro-patellar syndromes. Study of a continuous series of 140 operated knees]. AB - Surgical displacement of the tibial tuberosity has been performed in 140 cases over a 10-year period. Medial displacement with or without ventralization of the tuberosity gave excellent results in all 11 cases presenting with recurrent patellar dislocation. Anterior displacement of the tuberosity using a modified Maquet procedure was performed in 129 knees presenting with femoro-patellar pain (chondromalacia patellae, femoro-patellar osteoarthritis). Indication for surgery was intractable femoropatellar pain. Surgical technique (isolated anterior translocation or anterior and internal translocation of the tuberosity) was selected according to clinical and radiological examination. Results were very good in 50% of cases, good in 30%, poor in 20%. No patient was made worse after the procedure. The complication rate was acceptably low, due to meticulous surgical technique. The overall good results in this series are related to strict selection of patients. PMID- 2603684 TI - [Treatment of major patellar instability. Results of the Fevre-Dupuis operation]. AB - In the treatment of recurrent subluxation and dislocation of the patella in adolescents and young adults, the authors describe a method consisting of: --a modified Roux procedure for internal transposition and advancement of the anterior tibial tuberosity; --the Lecene technic for over-the-top reinsertion of the vastus medialis on the lateral aspect of the patella. All the patients had a plaster cast for 10 days followed by rehabilitation until normal knee function was achieved. Stiff knees were mobilized under general anesthesia. Normal activity was progressively resumed 6 weeks after surgery. Out of the 31 patients (41 knees) available for objective follow-up evaluation, 26 were women and 5 men, with an average age of 19 years. The mean follow-up period was 9 and a half years with a minimum of 2 years and a maximum of 23. End results in terms of relief of pain, patellar stability and knee function were gratifying. Thirty knees were rated good, 8 fair and 3 poor. No recurrence of subluxation or dislocation was found. PMID- 2603685 TI - [Long-term results of the Krogius-Roux operation]. AB - The authors have reviewed patients treated with the operation of Krogius-Roux with a long follow-up, especially on the indication of recurrent dislocation of the patella. Thirty-nine patients out of 76 operations have been evaluated. PMID- 2603686 TI - Entrapment neuropathies of the foot. Electromyographic techniques. AB - Entrapment neuropathies frequently involve the foot. The diagnosis can be established by electrophysiological techniques for the exploration of muscles and nerves. Needle recording from the intrinsic foot muscles is a valuable asset in the detection of neurogenic syndromes. The motor and sensory nerve conduction velocities are determined using surface electrodes. The sensory nerve conduction study can be supplemented with somatosensory-evoked-potential studies. Based on these investigations, the location, severity and prognosis of the nerve lesion can be determined. In the presence of tunnel and compression syndromes involving the foot, studies of the tibial nerve (tarsal tunnel - Morton), peroneal nerve and sural nerve are of particular interest. PMID- 2603687 TI - Tibialis posterior tendon synovitis and rupture. AB - The anatomy of the tibialis posterior muscle and tendon is described. It is the main stabilizer of the hind foot. Clinical and radiographic signs of tibialis posterior tendon rupture and the various operative techniques used, are reviewed. The Cobb method, using half the tibialis anterior tendon passed through a hole drilled in the navicular into the tarsal tunnel and anastomosed to the proximal end of the tibialis posterior, seems to give results superior to other methods. PMID- 2603688 TI - Tarsal tunnel syndrome: clinical and pathological results. AB - The tarsal tunnel syndrome is a complex entity. The condition results from a compression of the posterior tibial nerve, either at its terminal or collateral branches, at the tibio-astragalo-calcaneal canal of Richet. A retrospective study of 27 consecutive cases, treated by epi- or perineural neurolysis, illustrates the variability of the clinical picture but fails to confirm the complete and immediate success of the intervention, as reported by the majority of authors. However, the long-term follow-up shows a significant improvement in the terminal latencies of the posterior tibial nerve at 2 years post-surgery. A pathological study of 20 cadaveric feet discloses microscopic anomalies in 22 of the 120 nerve biopsy specimens. PMID- 2603690 TI - [Could biomechanical factors affect the etiology of Morton's neuralgia?]. AB - In the literature mechanical factors are considered as the most frequent etiology of Morton's disease. The pathology is a classical progressive fibrosis with rupture of nerve "fascicules" and/of arterioli, without nerve proliferation and without specific inflammatory factors. The deep intermetatarsal ligament and the bursae between the metatarsal heads are probably the most important factors in nerve irritation. In the literature there are few precise descriptions of the mechanism of irritation of the nerve, either by the bursae between the metatarsal heads, by the deep intermetatarsal ligament, or by the tendons of the lumbrical muscles which are close to the nerve. The aim of this study is an analysis of the mobility of these structures in both planes, by radiological evaluation in the erect position, after implantation of radiopaque pellets. The authors also present an hypothesis on the mechanism of the lesion. PMID- 2603689 TI - [True neurolysis in the treatment of Morton's neuroma]. AB - The authors consider Morton's neuroma as a tunnel syndrome, the most likely etiology being the compression of the nerve by the intermetatarsal ligament. Therefore, they have treated Morton's disease by decompression of the intermetatarsal nerve via a dorsal approach. They operated 45 patients, 82% of whom were women. In 85% of the cases, a large neuroma was found and they did not find the theoretical predominance of the 3rd intermetatarsal space; 9 times in 10, the treatment consisted in epineural dissection of the nerve and its collaterals at the bifurcation. In 84% out of the cases, the result was satisfactory; associated pathology was treated at the same time. The authors discuss the results and emphasize that, in case of failure, a simple neurectomy may be used. PMID- 2603691 TI - [A misdiagnosed disorder: syndrome of the musculocutaneous nerve of the foot]. AB - The syndrome of the pedal dorsal cutaneous nerve (described by one of us in 1979) is caused by irritation of the nerve in its course at the dorsum pedis. This is a rather frequent syndrome, often overlooked. It is manifested by a distinct association of atypical pain at the dorsum pedis and in the foot. After a review of 10 cases and a literature survey, the authors describe the characteristic signs of this syndrome. There are many factors at the origin of this pathology: static deformities (pes cavus anterior, valgus calcaneus, hallux valgus), local trauma or repeated microtrauma (ill sitting shoe). The diagnosis is essentially clinical, based on a positive Tinel sign along the course of the nerve and on the result of a trial infiltration of the region. The treatment is initially conservative with correction of deformities, adaptation of shoes, and local infiltration with corticosteroids. The neurolysis (performed in 4 cases because of persistent pain), showed dystrophic fibrosis. Such histologic lesions are an argument for considering entrapment as a potential cause of the syndrome. PMID- 2603692 TI - [Pathology of the anterior peroneus tendon and that of the intermetatarsal bone]. AB - The inconstant peroneus tertius is the fourth muscle in the antero-lateral aspect of the leg. Its tendon crosses the fourth tendon of the extensor hallucis brevis on the dorsal aspect of the cuboido-metatarsal joint. If an impingement occurs it may provoke a painful condition and a typical synovial cyst. The anatomy and the pathology of the condition are described. The treatment is very simple: the inconstant tendon should be removed when it produces symptoms. An accessory bone, the intermetatarsal bone, located at the proximal part of the first intermetatarsal or intercuneiform space, may have various shapes. It can provoke pain in the first space when pressure is exerted on capsulo-ligamentous structures or on neuro-vascular elements. The treatment is excision of the accessory bone. PMID- 2603693 TI - [Syndrome of compression of the external saphenous nerve (or the sural nerve)]. AB - The authors describe a new canal syndrome, which they call the "superficial sural aponeurosis canal syndrome" or "sural nerve tunnel syndrome". Mostly seen in sportsmen, it was observed in this case in the context of a myositis ossificans circumscripta of the tendo-muscular junction of the heel. The clinical signs are caused by compression of the sural nerve where it passes through a nonextensible tunnel formed by the fold of the posterior sural aponeurosis. This is distinguished from a loge syndrome; the most typical clinical sign is increased pain in the territory of the sural nerve during plantar flexion of the ankle; in this position reduced sensory conduction velocity is measured. The treatment consists in a section of the fibro-aponeurotic arch. PMID- 2603694 TI - Fracture of the coracoid process of the scapula with acromioclavicular separation. Case report and review of the literature. AB - A case report of a coracoid fracture of the scapula with acromioclavicular separation is presented. The treatment consisted of surgical reduction and fixation of the acriomioclavicular separation and of the coracoid fracture. After healing of the acromioclavicular separation and the coracoid fracture the left shoulder was asymptomatic with a full range of motion. PMID- 2603695 TI - Skeletal tuberculosis. Two case reports with a delay in diagnosis. AB - The presence of Mycobacterium tuberculosis in the olecranon simulated a "warm" bursitis. In another case a stiff knee due to osteitis in childhood was treated with an arthrodesis because of a confusing story of new trauma. Reactivation of previously unrecognized oseoarticular tuberculosis followed. Both patients had negative cultures in ordinary medium at the time of the onset of symptoms. PMID- 2603696 TI - The promontorial window. PMID- 2603697 TI - [Traumatic lesions of the ossicles]. AB - In 1957, Plester and Thorburn, independently, published their first reports on surgical correction of posttraumatic ossicular lesions. A large number of papers have appeared on this subject. The authors report their experience of 22 cases of traumatic ossicular lesion operated at ENT and Oto-Neurology Department of Lille University. PMID- 2603699 TI - [Sudden death due to undiagnosed congenital laryngeal cyst]. AB - Indicating signs of congenital cysts of the larynx are inspiratory stridor, dyspnea, weak cry, feeding difficulties. Complete or partial absence of such symptoms does not refer to a true congenital cyst. A false diagnosis could occur, due to small directive clinical signs. A relevant observation is communicated. PMID- 2603698 TI - [Mesenchymal chondrosarcoma]. AB - A case is presented of mesenchymal chondrosarcoma. This extremely rare tumor has a characteristic histology. The prognosis is poor. Radical surgery is essential. A lifelong follow-up is recommended. PMID- 2603700 TI - [The Audiant Bone Conductor. Clinical experience in 2 patients]. AB - In this paper we present you our clinical experience of 2 cases in which we implanted the Audiant Bone Conductor (by J. Hough). Our conclusion is that we should be very careful in making the decision to do such an implant; indications and limitations should be known by every surgeon who intends to do an implant. PMID- 2603701 TI - Safety of labetalol-induced controlled hypotension during middle ear microsurgery. AB - In order to study the influence of labetalol on the peroperative oxygenation during deliberate hypotension, 50 patients undergoing middle ear microsurgery were randomly divided in two groups of 25 patients; one group receiving labetalol to induce hypotension, the other group receiving placebo in a double blind manner. In the group receiving labetalol the arterial oxygen tension (PaO2) decreased significantly 5 minutes after the intravenous bolus injection. Within 30 minutes the PaO2 returned to the starting level. The arterial carbon dioxide tension (PaCO2) increased within 5 minutes and also returned to the initial level after 30 minutes. These changes were absent in the control group. It is concluded that, although labetalol produces a statistically significant change in PaO2 and PaCO2, this finding has only minor clinical implications and so labetalol remains a safe drug to be used for the induction of deliberate hypotension during middle ear microsurgery. PMID- 2603702 TI - Blue nevus of the maxillary sinus. An immunohistochemical and electron microscopic study. AB - We studied a case of blue nevus of the maxillary sinus by immunocytochemical and electron microscopic techniques. Blue nevus has not been reported previously to occur in the maxillary sinus. The melanocytic nature of this lesion was established based upon the ultrastructural demonstration of pre- and melanosomes, and the presence of S100 protein immunoreactivity in the pigmented cells. Histogenetic aspects of the blue nevus of the maxillary sinus are discussed and an origin in multipotential undifferentiated cells is postulated. PMID- 2603703 TI - [Retrobulbar neuritis in an isolated sphenoidal mucocele]. AB - The authors describe the evolution of a mucocele of the sphenoidal sinus to a reversible retrobulbar neuritis. They discuss the surgical treatment by trans antro-ethmoidal way. PMID- 2603704 TI - Difference in TcB readings between full term newborn infants born vaginally and by cesarean section. AB - We studied the influence of method of delivery on TcB readings at the forehead and sternum in full term neonates in the first week of life. Our present study demonstrated that TcB readings at the forehead and sternum of the infants delivered by cesarean section were significantly lower than readings from infants delivered vaginally without complications, from day 1 to day 7 of life (p less than 0.05). This is probably due to the decreased placental transfusion at cesarean section. The present study suggests that the degree of placental transfusion or time of cord clamping may be more influential than meconium passage or weight loss on serum bilirubin levels in the first week of life. PMID- 2603706 TI - Bone mineral content of appropriate and light for gestational age preterm and term newborn infants. AB - Bone mineral content was measured by single photon absorptiometry at the right mid humerus of 122 appropriate and 35 light for gestational age newborn infants born after 26 to 42 weeks of gestation. Bone mineral content was 2.4 times greater at the mid humerus than at the distal radius. Even in extremely low birth weight infants reproducible measurements were possible at the mid humerus. Light for gestational age infants showed a lower bone mineral content than appropriate for gestational age infants when bone mineral content was related to gestational age. When related to birthweight (g) bone mineral content showed a similar linear relationship in light for gestational age (mg/cm = 44.2 + 0.037 weight) and appropriate for gestational age (mg/cm = 39.4 + 0.040 weight) infants. For all 177 infants the relationship was mg/cm = 32.3 + 0.045 weight (r = 0.91). It is concluded that in growing preterm infants bone mineral content should be assessed in relation to weight rather than to age. PMID- 2603705 TI - Investigation of the effects of paralysis by pancuronium on heart rate variability, blood pressure and fluid balance. AB - The effects of pancuronium bromide on the cardiovascular system and fluid balance in preterm ventilated neonates was investigated. Infants were selectively paralysed if actively expiring. Their results were compared to a control group of similar gestational age, ventilated during the same study period, but who received no paralysing agent. There was no significant difference in the blood pressure of the two groups. Treatment with pancuronium was not associated with differences in blood pressure variability. All paralysed infants showed a significant reduction in heart rate variability which persisted during treatment. This was not present in the control infants. Paralysed infants, despite fluid restriction, had evidence of fluid retention, being significantly heavier than the control babies from day 3 onwards and above their birthweight by day 7. No paralysed or control infant developed a pneumothorax or renal failure. We conclude that selective treatment with pancuronium is without adverse effects on blood pressure but strict attention to fluid balance is essential. PMID- 2603707 TI - Auditory function after continuous infusion of gentamicin to high-risk newborns. AB - Audiometry was performed at four years of age in 69 of 105 surviving children who had received continuous intravenous infusion of gentamicin during neonatal intensive care. A hearing loss of 20 dB was found in 2 of them (3%), corresponding to that shown in other studies of survivors following neonatal intensive care. Free field audiometry performed in another 7 children and questionnaires returned from 13 of the remaining 29 gave no suspicion of hearing loss. Thus there is no indication that continuous 24 hours intravenous infusion of gentamicin causes more hearing impairment than intermittent intravenous or intramuscular administration. PMID- 2603708 TI - Transcutaneous bilirubinometry. Interinstrumental variability of TcB instruments. AB - We studied the interinstrumental variability of the transcutaneous bilirubin meter (TcB) in 35 high risk neonates, using eight commercially available TcB instruments. Our study showed that commercially available TcB instruments were stable and had little interinstrumental variability for repeated TcB measurements at the forehead, chest, and sternum. PMID- 2603709 TI - Relationship between exposure to icterogenic agents, glucose-6-phosphate dehydrogenase deficiency and neonatal jaundice in Nigeria. AB - In a study of the relationship between exposure to icterogenic agents, G-6-PD deficiency and severe neonatal jaundice (NNJ) (serum bilirubin greater than or equal to 205 mumol/l) in 234 Nigerian term male neonates, 106 infants with severe NNJ and 128 controls, it was found that 62.3% of the jaundiced infants and 13.3% of the infants without NNJ were G6PD deficient (p less than 0.01). The proportion of infants exposed to icterogenic agents in the two groups was very similar (p greater than or equal to 0.5). There was a strong association between exposure to icterogenic agents and NNJ in 83 G6PD deficient infants (p less than 0.01), but there was no association between exposure to icterogenic agents and NNJ in the whole group of 234 infants or in 151 infants with normal G6PD status. It is concluded that there is an association between genetically determined G-6-PD deficiency and exogenous agents in causing severe NNJ in Nigerian infants. PMID- 2603710 TI - Pharmacologically active levels of PGE1 in neonates with congenital heart disease. AB - In general, prostanoids act as local mediators, not as circulating hormones. A specific exception to this rule is the infusion of prostaglandin E1 in patients with ductus arteriosus-dependent pulmonary or systemic blood flow associated with congenital heart disease. We therefore measured prostaglandin E1 plasma levels by gas chromatography-mass spectrometry during effective infusion of prostaglandin E1 in 10 neonates. Prostaglandin E1 plasma levels ranged from 22 to 530 (median 56) pg/ml in these patients. Since prostaglandin E1 is not synthesized endogenously to any significant extent, these plasma concentrations constitute genuine circulating levels not confounded by the common problem of e vivo artifacts. If endogenous prostanoids (e.g. prostaglandin E2) are suspected as circulating mediators, plasma levels detected by reliable methods ought to be in the same range as prostaglandin E1 plasma levels in the present investigation. PMID- 2603711 TI - Estimating children's eating habits. Validity of a questionnaire measuring food frequency compared to a 7-day record. AB - A questionnaire measuring food frequency was validated against 7-day records of food intake in a group of 30 children, 2-16 years of age. Special emphasis was given to the ability of the questionnaire to estimate frequency of intake of foods of particular interest in diabetes mellitus. Fifteen children had insulin dependent diabetes; 15 were healthy. Comparison of the two methods regarding frequency of foods with high content of sucrose, protein, fat, fibres, nitrite or vitamin C showed a correlation of 0.52-0.76. The frequency of intake of some staple foods was often overestimated by the questionnaire, while the frequency of meat, sausage and some sweet snacks was underestimated. The use of the questionnaire to identify high or low consumers of the mentioned nutrients showed a rather low sensitivity (0.38-0.50), but a high specificity (0.86-1.0) when compared with results of the 7-day record. In our limited sample of subjects no systematic differences were found comparing sexes or diabetic and healthy children. A food frequency questionnaire may, in spite of some important reservations, be a useful tool for screening purposes when more time-consuming and resource-demanding methods cannot be used. PMID- 2603712 TI - Nutrition and health in Swedish children 1930-1980. Three nutrition surveys in a northern Swedish county. AB - In 1930 a nutrition survey was made of 1675 school children in the county of Vasterbotten in northern Sweden. In 1967 a second survey was carried out in the same area, covering 1411 children aged 4, 8 and 13 years. A third survey was carried out in 1980 of 572 children in the same age groups. In the first survey questionnaires concerning food consumption were used, in the two later surveys 24 hour recall of food intake was recorded. Underweight and iron deficiency anaemia were prevalent in 1930. Since then socio-economic conditions have improved dramatically and dietary habits have become more diversified. In the last study the average energy intake had decreased from 100 to 87% of the RDA. A slight increase in the prevalence of overweight among 13-year-old children was also noted. The fat intake was lower in 1980 than in 1967, but the P/S-ratio was still low (0.23). The iron intake reached a satisfactory level in the two later studies and no case of iron-deficiency anaemia was found in 1980. In spite of a relatively frequent sucrose intake dental health had improved as a consequence of other prophylactic activities. The malnutrition problems of 1930 have been eradicated but new nutritional problems, linked to the risk of developing obesity and health problems in adulthood such as coronary heart disease, call for new preventive strategies. PMID- 2603713 TI - Soft neurological signs and EEG pattern in rural malnourished children. AB - The present study was carried out in 208, 8-10 yr old male, rural, primary school children of Kashi Vidyapith Block, Varanasi. These children were examined for anthropometry, soft neurological signs and electroencephalographic pattern. It was found that the presence of soft neurological signs was related to the severity of malnutrition. The relationship between nutritional status and motor tasks showed that the performance in successive finger tapping, toe tapping, heel toe tapping, hand patting and alternating hand pronation supination in both hands while finger tapping with the right, was significantly affected. The EEG pattern in 16 children with soft neurological signs showed abnormalities in the form of slow and sharp waves, particularly in the frontal lobe, but also in the parietal and temporal lobes. The motor deficits were more marked on the contralateral side of the EEG abnormality. PMID- 2603714 TI - Monomeric calcitonin secretion in infants with congenital hypothyroidism. AB - We have determined CT levels in whole serum (iCT) and by an extraction method (exCT) in 25 infants affected by congenital hypothyroidism (CH)--11 athyreotic and 14 dysgenetic--at age 25 days, before the institution of therapy, and at age 2 years. In hypothyroid patients at age 25 days the iCT and exCT levels were similar to those found in controls of the same age. At age 2 years the iCT and exCT levels decreased in both groups of patients. However, whereas the levels of iCT in hypothyroids were similar to those found in controls of the same age, the levels of exCT were significantly lower in hypothyroids than in controls; moreover they were significantly lower in athyreotic than in dysgenetic patients. At this age, after calcium infusion, exCT levels significantly increased in dysgenetic but not in athyreotic patients. We hypothesize that CT deficiency in CH is due to increased degradation of human CT by the substitutive therapy, which, stimulating proteolytic enzymes, destroys the biologic activity of CT. An extraction procedure improves the sensitivity and specificity of the CT assay and it must be used when CT deficiency is suspected. In addition we suggest that the measurement of exCT levels after Ca infusion might be useful to distinguish dysgenetic from athyreotic patients. PMID- 2603715 TI - Ectopic thyroid: residual function after withdrawal of treatment in infancy and later childhood. AB - Plasma thyroxine (T4) and thyrotrophin (TSH) were estimated in 34 children identified by neonatal hypothyroid screening and subsequently found to have ectopic thyroid tissue on isotope scan. Before treatment plasma T4 ranged from 8 143 nmol/l and TSH from 39-1,230 mU/l. After one week off treatment during their second year, repeat T4 in 26 of these cases showed a significant correlation with the pre-treatment values (r = 0.57). However, only 3 of the 5 children with pre treatment T4 levels over 100 nmol/l at diagnosis had normal T4 values when retested. Similarly, when 10 children with pre-treatment T4 values over 65 nmol/l were retested off treatment at the ages of 5.8-8.2 years, only 4 had plasma T4 levels in the normal range. These results illustrate the wide range of thyroid function which can occur in children with ectopic thyroid tissue and indicate that some continue to have near-normal thyroid function for considerable periods. However, pre-treatment T4 results do not allow accurate identification of these latter cases. PMID- 2603717 TI - Atopy in children with and without a family history of atopy. II. Skin reactivity. AB - The influence of prolongation of breast feeding and postponement of introduction of solid food during infancy on skin reactivity at the age of five years was studied. At least one positive skin prick test result was observed in 23% of the 70 children with a family history of atopy and in 17% of the 58 children with no such history. Of the 26 skin-test-positive children, 54% exhibited positive reactions to cat dander and 42% to birch pollen. Of the 6 children with asthma, 6 with rhinitis and 17 with eczema, skin reactivity was observed in 66%, 66% and 35%, respectively. Contact with a cat during the first three to four months of life did not correlate with skin test positivity at the age of five years. Skin test positivity to birch pollen was more common in children born in January to February, probably because they were at a vulnerable age in their first birch pollen season in May. No preventive effect by the diet consumed during infancy was seen on subsequent skin test results in relation to common allergens. PMID- 2603716 TI - Atopy in children with and without a family history of atopy. I. Clinical manifestations, with special reference to diet in infancy. AB - The influence of a family history of atopy on atopic morbidity, and relationships between diet in infancy and allergic manifestations at the ages of one and five years were prospectively studied in 91 children. A control group consisted of 72 children with no family history of atopy. At the age of one year, atopic manifestations were found in 19% of 163 children, in 23% of those with a family history of atopy and in 14% of those with no such history. Skin problems were more common in children with a family history of atopy (43%) than in the control children (19%). Of the children with a family history of atopy, 23% had prolonged rhinorrhoea during infancy. The corresponding figure in children with no family history of atopy was 10%. Prolonged rhinorrhoea during infancy correlated with parental smoking only in children with a family history of atopy (47% vs. 18%). At the age of five years, atopic disease was found in 17% of 128 children, 24% of those with a family history of atopy and 9% of those with no such history. Atopic eczema was more common in children with a family history of atopy, irrespective of the diet consumed during infancy. Atopic signs were found in about half of all the children with a family history of atopy. If atopy had been present in the family, the child usually exhibited the same manifestation. Onset of atopic manifestations was not prevented or delayed. PMID- 2603718 TI - Decreased adherence of polymorphonuclear neutrophils in children with viral infection. AB - The adherence of polymorphonuclear neutrophils was examined in 16 children affected by enteritis, pneumonia, hepatitis and infectious mononucleosis. The results were compared with those obtained in 30 healthy adult volunteers and in 15 healthy children of the same age. Adhesiveness was significantly higher in adults than in healthy children, and significantly higher in healthy children than in children with viral infection. In 7 patients tested one month after regression of the disorder, PMN adhesiveness had returned to normal. PMID- 2603719 TI - C1q and C1 subcomponent complexes in otitis-prone and non-otitis-prone children. A prospective study of children during their first years of life. AB - Children with recurrent acute otitis media (rAOM) often show reduced C1q concentrations and an excess of (C1r-C1s)2 complexes. It is not known if such C1 aberrations precede development of rAOM or are a consequence of the infections. For this reason, serial investigation of C1q and C1 subcomponent complexes from birth until the age of three was performed in 113 children, 13 of whom developed rAOM. C1q concentrations at birth were found to be lower in the rAOM group than in children who did not experience acute otitis media, and were also correlated with age at the time of the first AOM episode. However, the wide variation of C1q within the groups precluded the use of C1q as a predictive marker. Excess (C1r C1s)2 complexes were consistently absent at birth. High concentrations were found in children with established otitis media and the complexes persisted in association with recurrent disease. In conclusion, the C1 aberrations characteristic of rAOM were mainly acquired as a result of infection. PMID- 2603720 TI - Borrelia infection in children. AB - All children (less than or equal to 15 years) admitted during 1986 to Sachs Children's Hospital and presenting signs of facial palsy and/or meningitis, or with a history of known tick bite followed by headache, fatigue and muscle pain, were investigated for antibodies to Borrelia in serum and cerebrospinal fluid. (The hospital's catchment area has a high incidence of tick-borne Borrelia infections.) Significantly elevated antibody titre was found in 15 of the 33 patients, in three cases only in cerebrospinal fluid. Eight of the 15 children had facial palsy, which was concomitant with meningitis in six cases. Intravenous penicillin was given to all 15 patients with positive antibody titre, and additionally to three severely ill small children with facial palsy and meningitis. Furthermore, two cases of erythema chronicum migrans, which is considered pathognomonic for Borrelia infection, were treated with penicillin perorally. Cases of Borrelia infection occurred throughout the year, but with a peak in August. To emphasize the variety of symptoms, three cases are presented in some detail. PMID- 2603721 TI - Cytotoxicity of galactose, tyrosine and methionine in cultured suckling rat hepatocytes: relation to liver immaturity. AB - Monolayers of suckling rat hepatocytes cultured for 24 hours were treated with galactose, I-tyrosine and I-methionine. The purpose was to study the reasons for the clinical improvement of patients with neonatal hepatitis after dietary restriction of these nutrients. Galactose, tyrosine, and methionine was cytotoxic on suckling rat hepatocytes, yet had no effect on adult rat hepatocytes. Furthermore, the pretreatment of suckling rat hepatocytes with dexamethasone ameliorated the cytotoxicity and induced a differentiation of the cells. These results suggested that the cytotoxicity resulted from the immaturity of suckling rat hepatocytes and therefore dietary restriction of galactose, tyrosine and methionine might be a useful treatment for patients with neonatal hepatitis. PMID- 2603722 TI - Child sexual abuse. Physical examination. AB - Twenty-nine children were subjected to physical examination as part of a population-based study comprising 41 children, aged 0-17 years, all assumed to be victims of sexual abuse. The hymenal opening was measured with transparent test tubes of known diameters using a new, simple and reproducible method. The examination was in no case performed under anaesthesia. A dilated hymenal opening and/or other physical evidence of trauma or disease were found in 19/29 children. Examination results evaluated in the light of anamnestic information indicated that sexual abuse had occurred in 10 cases but in only 3 of these cases the suspect was convicted. Additional studies are required to shed light on age related normal variations in genital anatomy. PMID- 2603723 TI - Health and development of 8-year-old children whose mothers abused amphetamine during pregnancy. AB - Sixty-five children whose mothers were addicted to amphetamine during pregnancy were followed prospectively until eight years of age, when they were tested in their homes. Only 21 children (30%) remained in the custody of their biological mothers. Their physical health, including growth, was normal. Their IQ and their performance in several psychometric tests were within normal limits. Increased incidences of aggressive behaviour and peer-related problems were found, especially in the groups that had been exposed to amphetamine throughout pregnancy. No correlation was found with socio-environmental factors. PMID- 2603724 TI - Severe adverse effects of maternal labetalol in a premature infant. PMID- 2603725 TI - Absorption of erythromycin in children with gluten intolerance. PMID- 2603726 TI - Early pregnancy varicella and associated congenital anomalies. AB - A case of congenital anomalies following varicella infection in the 8th week of gestation is described. Though the baby demonstrated a majority of the features characteristic of the congenital varicella syndrome and had positive immunofluorescent and ELISA tests for VZ specific antibodies, no vesicles or depigmented skin areas were seen. PMID- 2603727 TI - Vomiting as the main presenting symptom of acute asthma. AB - Vomiting as a dominant symptom in a patient with acute asthma is reported. The traditionally recognized triad of cough, tachypnea and wheezing were absent or trivial whenever this patient presented with persistent vomiting. A careful history, laboratory evaluation and a course of bronchodilators eventually ascertained that the episodes of vomiting were due to attacks of acute asthma. It is suggested that acute asthma be included in the differential diagnosis of recurrent and/or severe vomiting in children. PMID- 2603728 TI - Spondyloepiphyseal dysplasia tarda in Turner syndrome. AB - A girl with short stature is described in whom chromosomal analysis revealed a 45,X/46,XX mosaicism and in whom radiological investigations disclosed the diagnosis of X-linked spondyloepiphyseal dysplasia tarda. This is the first report of the occurrence of X-linked spondyloepiphyseal dysplasia tarda in a child with Turner syndrome. PMID- 2603729 TI - The mesencephalic reticular formation as a link in the cortical control of exploratory and goal-directed behaviour. AB - The general accepted concept about the MRF as an unspecific ascending activating system concerns only one of its multiple functions. Investigations on more than 100 hooded rats of the Long-Evans strain with small bilateral symmetric lesions in dorsal, central and ventral subnuclei of the MRF brought out the following results pointing to further important functions: 1. Each lesion type produced a different syndrome of parameter changes of the spontaneous open field behavior with some common tendencies of reduced ambulatory and exploratory activities. 2. Visual placing responses were strongly reduced or totally abolished after lesions without tendencies of recovery. 3. Changes of locomotion and muscular tonus were quite different or even opposite in dorsal, central and ventral types of lesions. 4. In four tasks of postoperative active avoidance acquisition or retention and performance of preoperatively learned tasks the impairments were different related to the lesion type including a different loss in brightness discrimination. The results support the hypothesis that MRF subdivisions participate differently in information selection, tuning and coupling information with goal directed movements of different type. Lesions severely disturb the proper use of some information for a cue, especially visual cues when they are in the anterior part of the mesencephalon. PMID- 2603730 TI - Changes of acid solubility and fluoride content of the enamel surface in children consuming fluoridated milk. AB - Changes of the acid solubility and fluoride content of the surface layer of the enamel of the first incisor of seventy-nine 9 to 10-year-old children living in a closed community were measured by the method of enamel biopsy at the 6th and 12th months of the consumption of fluoridated milk. Half-year after the beginning of consumption of fluoridated milk the acid solubility decreased significantly, while one-year-long consumption led to significant increase of the fluoride content of the enamel surface. PMID- 2603731 TI - The effect of Ringer solution induced extracellular volume expansion on kidney function. AB - The present study quantitated the effects of extracellular volume expansion on sodium and water excretion in 118 anesthetized dogs. The animals received a priming injection of 10 ml kg-1 Ringer solution i.v. which was followed by a constant Ringer solution infusion at a rate of 0.25 ml.min-1.kg-1 until the end of the experiment. Fifteen minutes after the start of the constant infusion the renal parameters were examined in 11 subsequent 15 min periods (the total time was 3 hours). Volume expansion produced no significant change in arterial blood pressure, glomerular filtration rate (GFR), plasma sodium and potassium concentration or, haematocrit, but did reduce the CPAH from 284 ml.min-1 to 218 ml.min-1 (the data were calculated for 100 gram wet kidney weight). There were constant significant increases in the urinary excretion rate from 0.84 ml.min-1 to 4.06 ml.min-1 and the 39% of the infused water was excreted during the experiment. Volume expansion also caused a significant increase in sodium excretion during the three first periods from 120 mumol.min-1 to 329 mumol.min-1 followed by a small but significant decrease. The sodium excretion at the end of the experiment was 221 mumol.min-1 and the 23% of the infused sodium was excreted in the course of the experiment. The increase of the water excretion during the volume expansion was associated with fall of the urine osmolality and the urine because hypoosmotic as compared to the plasma. We have provided evidence that vasopressin was not involved in the control of water excretion in our experiments. It is concluded that neither filtered sodium nor decreased aldosterone secretion can account for the increase in sodium excretion that occurs after Ringer solution loading in the dog. It has been proposed that a decrease in plasma protein concentration may decrease passive sodium reabsorption due to oncotic forces in the proximal tubule. The Ringer solution diuresis elicits a rise in medullary blood flow, thereby causing a washout of medullary sodium. This might dissipate the osmotic force for the back-diffusion of water from the collecting duct. Our studies indicate that the response of the diluting segments of the distal nephron to increased delivery of sodium depends upon the presence or absence of volume expansion. However the increase of the distal tubular loading activates the tubuloglomerular feedback which increases the proximal tubular reabsorption. Based on these assumptions our studies provide further evidence that the tubuloglomerular feedback regulates the blood pressure in the peritubular capillaries in the cortex around the proximal tubules. PMID- 2603732 TI - Effects of the lipolysis inhibiting agent beta-pyridylcarbinol (Ronicol) in acute myocardial ischaemia. AB - The antilipolytic, nicotinic acid analogue beta-pyridylcarbinol (Ronicol) has previously been reported to decrease the free fatty acid (FFA) concentration of the arteria-blood, and to moderate the FFA-uptake and O2-consumption of the myocardium; on this basis, the drug may be expected to exert a cardioprotective action. The cardiac effects of Ronicol were therefore studied on a self-control, 'single-vessel' coronary artery ligature dog model. The left anterior descending coronary artery (LAD) was prepared in the in situ heart of anaesthetized, thoracotomized animals. Following the control ligation, a stabilization period and Ronicol infusion (1 mg/kg iv. during 10 minutes), the LAD was repeatedly ligated. The duration of the individual occlusions was 10 minutes. Ronicol significantly decreased the arterial FFA concentration and the epicardial ST segment elevation; its antilipolytic and anti-ischaemic effects were protracted and were still observed 120 minutes after pretreatment. The drug did not decrease the inhomogeneity of ventricular depolarization in the ischaemic myocardium and in the dose applied it had no influence on the heart rate, arterial blood pressure, left ventricular end-diastolic pressure and left ventricular contractility (LV dP/dtmax). In the canine myocardial infarction model employed it was observed that the duration of the anti-ischaemic effect of Ronicol (1 mg/kg iv.) is about 120 minutes. It has the advantage that it does not possess the unwanted cardiovascular side-effects displayed by nicotinic acid observed by us too in this model earlier (Cardiol. Hung. 13, 33-41, 1984). PMID- 2603733 TI - Role of the substantia nigra in the behavioural-cardiovascular integration in the cat. AB - Electrical stimulation of the substantia nigra elicited complex patterns of response composed of somatomotor and circulatory changes. Increase in blood pressure associated with acceleration in heart rate was consistently produced by substantia nigra stimulation both in conscious and in anaesthetized cats. The respiration was either accelerated or arrested by the stimulation. Also self stimulation of the substantia nigra elicited pressor responses. Electrical stimulation of the nucleus of the tractus solitarius paired with self-stimulation of the substantia nigra, produced regular changes in the lever-pressing rate for self-stimulation. It is suggested that the substantia nigra is probably involved in the neural mechanisms coupling the circulatory changes with the somatomotor responses. PMID- 2603734 TI - Zinc as a possible mediator of signal transduction in T lymphocytes. AB - Our recent findings indicate that phorbol esters, the specific activators of protein kinase C induce the translocation of heavy metals (mostly: zinc) from the nucleus and mitochondria to the cytosol and microsomes of T lymphocytes. Phorbol ester treatment impairs the action of Ca-ionophores, this effect is mediated by intracellular heavy metal ions (most probably: by zinc). Zinc activates cytosolic protein kinase C, increases its affinity towards phorbol esters and contributes to its binding to plasma membranes. These results suggest that zinc may play a role in the "cross-talk" of second messengers and hence in signal transduction in T lymphocytes. PMID- 2603735 TI - Changes in the electrical activity of the stomach after partial resection of the pancreas and occlusion of the pancreatic duct. AB - The electrical activity of the stomach and duodenum of six mongrel dogs was studied under chronic conditions after partial resection of the pancreas and occlusion of the pancreatic duct. Changes in the electrical activity were observed only in the stomach, manifested in the form of groups of slow potentials with accelerated rhythm (over 7 cpm--tachygastria) or delayed rhythm (below 3 cpm -bradygastria). A definite dynamics was observed in the appearance and development of rhythmic disorganization. The duration of the groups of slow potentials with abnormal rhythm increased 10-12 days after surgery. Radioimmunological studies showed a postoperative increase in the glucagon level, paralleled by a decrease in the content of the C-peptide and insulin in the blood plasma. Influsion with insulin (0.5 IU i.v.) regulates the disorganized antral rhythm. The dysbalance in the insulin/glucagon ratio in the blood serum is assumed to be the probable mechanism of the rhythmic disturbances. PMID- 2603736 TI - Effect of the post-reserpine adrenergic block on thrombocytopoiesis and thrombocyte aggregation in rats. AB - The effect of the post-reserpine adrenergic block (2 mg/kg for 3 and 6 days) on thrombocytopoiesis, bone marrow megakaryocytes (MKC) and thrombocyte aggregation was studied. A slight decrease in thrombocytes and a significant inhibition of 75selenomethionine incorporation in the newly-formed thrombocyte, more pronounced after 6-day reserpine treatment, was observed. The megakaryocytogram of the rats treated with reserpine for 3 and for 6 days manifested a similar significant decrease in MKC--as a total number and their separate stages. Thrombocyte aggregation was significantly inhibited, especially after the 6-day treatment. The inhibition of the megakaryocytopoiesis is probably the result of reduced metabolic processes, while thrombocyte aggregation probably results also from the serotonin depletion in the thrombocytes and the increased adrenaline level in the blood--phenomena observed after treatment with reserpine. It is concluded that the normal functions of the neuronal unit of the adrenergic transmitter system are necessary for the formation of an adequate number of functionally valuable thrombocytes. PMID- 2603737 TI - Age-determined changes in the effects of a newly synthetized cholinesterase inhibitor on exploratory behavior, memory and striatal cholinesterase activity in rats. AB - The newly synthetized cholinesterase inhibitor C-8 (a structural analogue of physostigmine) at a dose of 4 mg.kg-1 exerted no inhibitory effect on the spontaneous locomotor activity in 2-, 10- and 22-month old male Wistar rats. Upon open field test, C-8 facilitated the process of habituation in the rats of all three groups. In a passive avoidance situation (step-down and step-through) C-8 had a favorable effect on the memory of 22-month old rats mainly. C-8 inhibited the cholinesterase activity in the striatum of 2-month old rats by 29%, in 10 month old rats by 73%, and in 22-month old rats by 30%. PMID- 2603738 TI - Long-term locomotion regimens affect EEG paroxysmal activity, behaviour and sex hormone secretion in female rats. AB - The study deals with the changes of the excitability of CNS in the course of the ovarial cycle under the influence of long-term locomotion regimens. The excitability of the CNS was evaluated by the spontaneous EEG paroxysmal activity and by the changes in certain behavioural states (alertness, exploration and quiet wakefulness). The changes of the excitability (as assessed by EEG and behavioural features) were correlated with the effects of the locomotor regimens on the serum levels of ovarial hormones. The results suggest that long-term locomotion regimens alter the excitability of the CNS during the ovarial cycle. Running exercise was found to ameliorate the functional state of the nervous system by increasing the activation threshold, whereas restricted locomotion increases the sensitivity of the CNS. PMID- 2603739 TI - Perception time and reaction time. AB - Two experiments were performed in order to examine the possible contribution of visual perception time in motor response time under conditions of pursuit eye movements. Subjects had to follow with their eyes a light spot moving horizontally along a reference scale at a constant velocity of 14 degrees/s. Stimuli (the disappearance of the moving spot) were presented randomly at distances of 11.3, 17.7 and 24.2 angular degrees from the onset of motion. In Experiment 1 subjects had to report verbally the scale division at which the stimuli were presented. In Experiment 2 subjects had to press a button as quickly as possible after stimulus presentation. No relationship between visual perception time and motor reaction time was found. PMID- 2603740 TI - A method for continuous infusion and blood sampling in unanaesthetized rats. AB - We describe a technique for long-term cardiac catheterization and blood sampling in unanaesthetized rats. The use of metabolism cage and swivel joint-equipped infusion system allows also continuous infusion of fluids in freely-moving animals. PMID- 2603741 TI - Oxytocin plasma level in the lactating sows--effect of suckling. AB - Oxytocin concentration in the peripheral blood was measured by RIA during suckling period in lactating sows (n = 8). Blood samples were taken from the jugular vein around the clock for every 2 h on day 5, 10, 15, 20, 25, 30 and on day 35 of lactation. Besides that blood samples were collected more frequently during suckling periods. Oxytocin plasma concentration was very low and in most cases it was on a border of sensitivity of our method (3 pg/ml). Marked but short lasting rise of oxytocin was observed only during a period of initial massage of the udders by the piglets. This rise observed in all studied pigs was higher (p less than 0.01) compared to the values before the massage on the onset of lactation only, and was 14.6 +/- 4.2 pg/ml and 6.4 +/- 1.2 pg/ml on day 5 and day 10 of lactation, respectively. In all other studied days in a few cases only suckling stimulated the release of oxytocin over its basic concentration. Mean values (+/- SEM) of oxytocin in blood samples collected during massage of udder on day 15, 20, 25, 30 and day 35 were 3.7 +/- 0.5, 4.2 +/- 0.8, 4.9 +/- 1.1, 3.2 +/- 0.4 and 3.0 +/- 0.6 pg/ml plasma, respectively. There was no relationship between the size of the litters and neither basic level of oxytocin nor its blood concentration during suckling (r = 0.13). PMID- 2603742 TI - Effect of indomethacin and vasotocin on oviposition in the hen (Gallus domesticus). AB - The interrelationship between prostaglandins (PG) and vasotocin (AVT) in the oviposition of the domestic hen was investigated. Single or combined injections of indomethacin (IND), an inhibitor of PG synthesis, and AVT gave delay or induction of oviposition. Injection (i.m.) of IND (5 mg/kg) 5 h before oviposition resulted in 15.1 h (+/- 0.93) delay of oviposition. Injection (i.v.) of AVT (0.1 microgram/kg) 2.5 h before oviposition caused premature oviposition within a few minutes (3.1 +/- 0.2). Combined injection of IND and AVT at 5 h and 2.5 h, respectively, before oviposition caused the delay of oviposition (15.8 h +/- 0.8). The results indicate that IND blocked the induction of oviposition by AVT. PMID- 2603743 TI - Influence of acute stress on the pineal activity during day- and nighttime. AB - Ovariectomized, steroid implanted female ewes were used as a model for studying the effect of acute isolation and confinement stress on the pineal activity during day and nighttime under artificial luteal phase conditions. Male and female intact buffaloes were employed as well, with the aim to establish the influence of another perturbation (venous catheter insertion) on the melatonin levels during daytime. Stress appeared to influence pineal melatonin secretion in controversial manner, namely, decreasing further the low indole levels during the day, while elevating the peripheral concentrations at night, though the initial response to stress during daytime was a transient elevation in melatonin levels. There are no indications that the adrenals are directly involved in the changes observed. Possibilities for different mechanisms of melatonin secretion and release in different species are considered. PMID- 2603745 TI - Reproduction in the red deer female and the effect of oestrogens on the antler cycle and behaviour. AB - Red deer (Cervus elaphus) is a seasonally breeding mammal. The season of reproduction is probably regulated by photoperiod. The rut and the majority of conceptions occur in October. If hind is not allowed to mate the oestrus is repeated at an interval of about 13.5 days. In captivity the mating season is more prolonged and the calving season is extended. The length of gestation is about 235 days. The fat % of milk varies between 6.6 and 17.4. A hind in good condition may attain puberty as 16.5 month old. The smaller doses of stilboestrolum dipropionicum (S, 150-250 mg) induced mainly a female type of sexual behaviour or oestrus. The bigger and more prolonged administration of S (250-300 mg, given twice with a monthly interval) induced a strong male sexual behaviour e.g. roaring, chasing a hind in oestrus, mouting a hind in oestrus or a dummy sprinkled with pheromones and performance of an ejaculatory peak (M). During M the hind was in an almost vertical position and a single ejaculation of saliva was always observed. The artificially induced antlers of hinds without hormonal treatment became broken and their regrowth was very small. After S the velvet was always shed. After larger doses of S the casting was more delayed and the next antler growth was bigger. PMID- 2603744 TI - Pharmacokinetics and pharmacodynamics of terguride following intramuscular administration in cows and goats. AB - The pharmacokinetics of intramuscular terguride (transdihydrolisuride) was evaluated in a single-dose study in cows (doses 100, 62 and 31 micrograms/kg b.w.) and goats (dose 100 micrograms/kg b.w.). A radioreceptor assay was used to quantitative plasma terguride concentrations. The peak plasma concentrations of terguride were attained within 0.6 h of the drug administration and then decreased monoexponentially with half-life of 1.3 h (cows) and 2 h (goats). The pharmacokinetics of terguride in cows is nearly linear. Pharmacodynamics of terguride was expressed as reduction in plasma prolactin levels. Maximal decline in prolactin was observed 3-4 h following terguride administration and the effect lasted for about 24 h. PMID- 2603747 TI - Role of cholecystokinin in feeding and lactation. AB - The aim of this investigation was to study the release of cholecystokinin (CCK) in connection with feeding and lactation and to investigate the involvement of CCK in the regulation of food intake. For this purpose a method based on high performance liquid chromatography and subsequent radioimmunoassay (RIA) for the determination of CCK in plasma was developed. CCK was also determined in the cerebrospinal fluid (CSF) by RIA and is referred to as CCK-like immunoreactivity (CCK-LI). Different molecular forms of CCK in dog and rat plasma have been determined. These were found to differ from those in the CSF, suggesting that the CCK measured in plasma and CSF are derived from different sources, i.e. the gut and brain. CCK was released into plasma in response to feeding in dogs and rats and in response to suckling in lactating animals. The release of CCK is under vagal control. Thus, electrical vagal stimulation of anaesthetized rats increased plasma levels of CCK, and abdominal vagotomy abolished the suckling-induced release of CCK. Lesions of the lateral midbrain, which disrupt the oxytocin mediated milk-ejection reflex, were also found to block the increase in plasma CCK in response to suckling. Intraperitoneal (i.p.) injection of CCK octapeptide (CCK-8) decreased food intake in food deprived male rats in doses which resulted in plasma concentrations within the physiological range. Intracerebral, but not i.p., injection of a low dose of a CCK antagonist, reversed the effect of peripheral CCK-8 on food intake as did i.p. injection of peripheral CCK A receptor antagonists. Thus, the mechanism by which i.p. CCK-8 inhibits food intake may involve both peripheral and central CCK receptor mechanisms. The concentration of CCK-LI in the CSF decreased after food deprivation and increased after feeding or i.p. CCK-8. Intraperitoneal injection of peripheral CCK antagonists prevented the increase in CCK-LI in the CSF and the inhibitory effect of i.p. CCK-8 on food intake. These data indicate that peripheral CCK receptor mechanisms induce a release of CCK in the brain. During the hyperphagia of lactation, plasma but not CSF levels of CCK were increased in the rat. Food deprivation markedly decreased the concentration of CCK in plasma and CSF; and the levels were restored in CSF, but not in plasma, after 1 h of feeding. Removal of the litter decreased food intake and increased the concentration of CCK in the CSF, but not in plasma. Lactating rats were less sensitive to the inhibitory effect of i.p.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2603746 TI - Counter current transfer and back transport of 3H-PGF2 alpha in the cow's broad ligament vasculature ipsilateral and contralateral to the corpus luteum. AB - Eight cows of similar age (5-7 years) were chosen for the experiment. Isolated reproductive tract was supplied with autologous oxygenated and heated (40 degrees C) blood through the uterine artery and ovarian artery. 3H-PGF2 alpha in total dose of 2 MBq (10(7) cpm) was injected into each of the uterine lumen of isolated organ. Blood samples were collected at 5 min intervals during 120 min of experiment using cannulae inserted into the branches of uterine arteries about 1 cm below the horns and from ovarian arteries inserted 0.5 cm below the ovaries. The concentration of 3H-PGF2 alpha found in blood plasma taken from uterine artery or from ovarian artery on the side with active corpus luteum (CL) was significantly lower (p less than 0.001) compare with contralateral side to active CL. Radioactive PGF2 alpha found in branches of uterine arteries on both ipsilateral and contralateral side to CL was significantly higher (p less than 0.001) compare to ovarian artery of the same side. It is concluded that absorption of 3H-PGF2 alpha from uterine lumen into venous blood as well as its counter current transfer in area of broad ligament vasculature were reduced on the side of uterine horn with active CL probably as an effect of estrogen:progesterone ratio on vascular constriction in area of uterine vasculature. PMID- 2603748 TI - Electrophysiological characteristics of the Necturus proximal duodenal mucosa: effects of ion substitutions. AB - Voltage-sensitive glass micro-electrodes were used to determine the electrical characteristics of Necturus proximal duodenal epithelium. Some comparative experiments with amiloride were performed with gastric antrum. The apical and the basolateral cell membrane potential differences in duodenum averaged -32 mV and 34 mV (cell negative) respectively. The transepithelial potential difference was 2 mV (lumen negative). The EMF across the apical cell membrane was -29 mV and that across the basolateral cell membrane -39 mV. The transepithelial resistance (Rt) of 63 omega cm2 and the paracellular pathway resistance (Rs) of 80 omega cm2 are of magnitudes similar to that previously reported for more distal amphibian small intestine. The apical and basolateral cell membrane resistances, however, were lower than those reported for distal small intestine. Ion permeabilities for Na+, K+ and Cl- across the apical cell membrane were calculated from ion substitution experiments. The permeability sequence across the apical cell membrane was PK:PCl:PNa 3.02:1.31:1.00. Luminal amiloride (10(-4)M) was without significant effect, further indicating a low duodenal membrane conductance for Na+. The low conductances for K+, Na+ and Cl- suggest that the major ion transport modes across the apical duodenal cell membrane are electroneutral in nature. In contrast, amiloride caused a marked increase in the transmembrane potentials in the antrum. PMID- 2603749 TI - Field potential analysis of the cortical projection of the central lateral nucleus in the cat. AB - A previous field potential study has indicated a monosynaptic projection of fibres from the central lateral nucleus (CL) to the mid-suprasylvian gyrus (MSSG). The present study, which is based on an analysis of current source density (CSD), aims to investigate further the sites of major localized synaptic activities in different layers of the MSSG after electrical stimulation in the CL. An initial positive surface potential was evoked in the MSSG with a latency of 3-5 ms and followed by a large negative potential with a peak latency of 8-15 ms. The initial positivity was only found in the rostral part of the MSSG, which corresponds to area 5. The positivity reversed in deeper layers. The CSD analysis showed a sink at a depth from 650 to 1050 microns. A corresponding source was found more superficially at 400-600 microns. This indicates that CL fibres have an excitatory synaptic termination on the soma or proximal dendrites of neurons in layers III and IV. The surface negative potential reversed at the border between layers II and III, suggesting a superficial CL projection. The CSD analysis of potentials in superficial layers showed a sink appearing between the pial surface and a depth of 350 microns, and a source lying in layers below. This indicates a depolarization of apical dendrites of cells in layers II and III. The superficial sink appeared in a large part of the MSSG. Application of a solution of 0.5% gamma-aminobutyric acid (GABA) on the surface of the cortex blocked the superficial sink and source and revealed a prominent sink current in layers III and IV in agreement with a deep termination of CL fibres. Application of a solution of 25 mM DL-2-amino-5-phosphono-valeric acid (APV) abolished CL-evoked cortical responses indicating that N-methyl-D-aspartate (NMDA) receptors are involved in the cortical activation. The CSD analysis confirms that CL has a wide superficial projection to the MSSG. It also confirms a deeper monosynaptic projection from CL to area 5. PMID- 2603750 TI - Large capacity in man for effective plasma volume control in hypovolaemia via fluid transfer from tissue to blood. AB - Compensatory absorption of extravascular fluid from skeletal muscle and skin into the circulation in response to experimental hypovolaemia was studied by plethysmographic technique in the upper arm of man. Lower body negative pressure (LBNP) of 90 cmH2O, applied for 10 min, served to produce rapid and prominent hypovolaemic stress as indicated by prompt decrease in central blood volume (external recording of [99Tcm]erythrocyte activity) followed by marked tachycardia. The arm concomitantly showed an initial mobilization of regional blood, an increased vascular resistance, and a continuous net transcapillary fluid absorption, i.e. similar responses as reported in animals upon haemorrhage. The absorption of extravascular fluid, validated by simultaneous analyses of changes in tissue volume and in regional blood volume [99Tcm]erythrocyte activity), was rapid and averaged 0.13 ml min-1 100 ml-1 soft tissue during the 10 min of LBNP exposure. In some subjects with symptoms and signs of pronounced circulatory stress fluid was transferred twice as fast. Separate experiments indicated that the rapid fluid flux was causally linked to the existence in the studied tissue of a large transcapillary hydraulic conductance. It is concluded that man possesses a surprisingly great capacity for compensatory circulatory refill via fluid transfer from tissue to blood. The data in fact suggest that in true states of hypovolaemia as much as 500 ml might be gained into the circulation in only 10 min. PMID- 2603751 TI - Renal and circulatory effects of medullipin I, as studied in the in-vivo cross circulated isolated kidney and intact Wistar-Kyoto (WKY) rat. AB - The renal medulla harbours powerful humoral antihypertensive mechanisms, as earlier explored in unclipping experiments on renal hypertensive rats or in normotensive isolated kidneys cross-circulated at increased perfusion pressures from 'donor rats', in which renal function also seemed to be affected. Injection of the renomedullary factor medullipin I (Med I; formerly ANRL) mimics these haemodynamic responses, and Med I seems to be one of the most important mediators of the depressor effects. The present study was performed to analyse further the haemodynamic and, particularly, the renal effects of Med I, using anaesthetized intact WKY rats and constant-pressure perfused (90 mmHg) isolated WKY kidneys, cross-circulated by these intact 'donor' rats. Mean arterial pressure (MAP), heart rate (HR) and renal function were followed for one 30-min period before and two 30-min periods after injection of 1 mg Med I (M; n = 7) or an equal volume of saline as control (C; n = 13). In the intact 'donor' WKY, MAP and HR remained largely constant in C during the three periods, being 126 +/- 5, 125 +/- 5, and 120 +/- 5 mmHg, while MAP fell in the M group after Med I, from 121 +/- 5 to 107 +/- 7 and 107 +/- 5 mmHg (P less than 0.05), and also HR tended to decrease in M. Renal resistance (RR) fell while renal plasma flow (RPF) and glomerular filtration rate (GFR) increased significantly (P less than 0.05) after Med I in the M donor rats despite their MAP reduction. However, in the constant-pressure perfused, cross-circulated kidneys the RR, RPF and GFR changes were clearly more pronounced (P less than 0.01) and also diuresis, natriuresis, osmolar excretion and osmolar clearance increased significantly after Med I (P less than 0.01). In conclusion, the present results support the view that Med I not only has important and long-lasting depressor effects but also affects renal function in important ways, inducing vasodilatation and increasing GFR, RPF, diuresis and sodium-osmolar excretion. PMID- 2603752 TI - In-vitro stimulation of the rat epitrochlearis muscle. III. Endogenous levels of branched-chain amino acids are maintained during acute contractions even in the absence of an exogenous supply. PMID- 2603753 TI - Mental stress and adrenaline increase plasma growth factor activity in humans. PMID- 2603754 TI - NGF primed spleen cells injected in brain of developing rats differentiate into mast cells. AB - The aim of this work was to study the topographic distribution and the morphological behaviour of nerve growth factor (NGF) primed spleen cells injected into the lateral ventricles of developing rat brain. Serial coronal brain sections showed that these transplanted cells acquire phenotypical characteristics similar to those of mast cells (MCs) and that they enhance local neovascularization. These results, together with the observation that these cells are located in proximity to the hippocampus, a brain tissue which contains one of the highest levels of NGF, provide a model for studying the relationship between NGF and MC differentiation and secretion. PMID- 2603755 TI - Cell number, tissue thickness and protein content as measures for development and variability in cultured neocortex explants. AB - The development of neuronal number, explant thickness and amount of protein was studied in several series of rat neocortex explants, cultured up to 21 days in vitro (DIV). In contrast to the dimensions of the explant, which rapidly stabilized, the amount of protein showed a prolonged increase with age in vitro. The number of neurons initially tended to decrease until a constant level was reached from 14 to 21 DIV. These findings are in good agreement with previously described cytoarchitectural characteristics. The present data also provided an opportunity to calculate the variance for various parameters within and between culture series obtained from different rats. Especially for the amount of protein, the variance between culture series appeared to be larger than within culture series. This difference was present already at the onset of culturing and persisted during development in vitro. Implications of these findings for experimental design are discussed. PMID- 2603756 TI - Synaptic density of caudate-putamen and visual cortex following exposure to ethanol in utero. AB - Pregnant Long-Evans rats were fed a liquid diet containing ethanol (30% of total calories) during days 3-19 of gestation. Controls were given ad libitum access to liquid diet lacking ethanol, or pair-fed isocaloric amounts based on consumption by the animals in the ethanol group. Brain development of female offspring was evaluated by analysis of electron micrographs of caudate-putamen and visual cortex. Numbers of presynaptic terminals and synaptic junctions (synaptic density) per unit area were compared for 14- and 28-day-old offspring of dams from the three treatment groups. Synaptic density of the caudate-putamen and visual cortex was not affected by ethanol at 14 or 28 days. Although exposure to ethanol during a period comparable to the first two trimesters of human development with minimal or no undernutrition did not affect numerical density of synapses in visual cortex or caudate-putamen, synaptogenesis of caudate-putamen was altered in offspring of pair-fed animals. PMID- 2603757 TI - Sexual differentiation of mesencephalic neurons in vitro: effects of sex and gonadal hormones. AB - In order to study the influence of gender on the development of transmitter uptake by dopaminergic neurons, dissociated cell cultures were raised separately from male and female midbrains of gestational day 14 rats. It was ascertained by use of specific inhibitors and by autoradiography that the uptake of [3H]dopamine was restricted to neurons immunoreactive for tyrosine hydroxylase and that these neurons have dopaminergic properties. The uptake capacity was higher in male than in female dopaminergic neurons by a factor of 1.5. This sexual dimorphism in dopamine uptake was present in cultures of tissue removed before the perinatal rise of testosterone occurs in males, and was present even in the absence of hormonal additives to the culture medium. It therefore appears to be independent of the presence of gonadal steroids. It occurred likewise in cultures raised with serum-supplemented and serum-free medium, which may indicate that glia are not decisive in generating these differences. In addition, sexual differences were found regarding hormone responsiveness. Whereas testosterone and dihydrotestosterone were ineffective, estradiol was seen to promote dopamine uptake in female but not in male neurons. The results would suggest that mesostriatal and/or mesolimbic dopaminergic systems assume an early role in the development of some sexual dimorphisms of the brain. PMID- 2603758 TI - Premetamorphic effects of thyroid hormones on tadpole sensory ganglia. AB - Tadpoles at premetamorphic stages of development were used to compare the precocious responses of lumbar dorsal root ganglia (DRG) and hindlimb bud (tissues destined for growth) with the responses of tail DRG and tail muscle (tissues destined for resorption) following exogenous administration of triiodothyronine (T3) and thyroxine (T4). Responses to intraperitoneal (i.p.) hormone treatment were assessed at varying times by injection of [3H]leucine i.p. and determination of 3H-labeled protein in tissues after an additional 1.5 hr. Incorporation of [3H]leucine in lumbar DRG and hindlimb bud was markedly stimulated by either hormone. T3 and T4 effects were both maximal at 0.3 nmol/g body wt although, as examined in lumbar DRG, the response to T4 was more rapid and of lesser magnitude than that to T3. By contrast, incorporation in tail DRG and tail muscle was significantly depressed in response to T3 and was unaffected by T4. Co-injection of T3 and T4 (either 1:1 or 1:6 as occurs during the peak surge of circulating thyroid hormones during metamorphic climax) did not produce an additive effect; the hindlimb bud response was reduced while the lumbar DRG, tail DRG and tail muscle responses to the individual hormones were virtually eliminated. The present data suggest that the responses of lumbar and tail sensory neurons to thyroid hormones parallel the responses of their peripheral target tissues. PMID- 2603759 TI - Polyamines induce precocious development in rats. Possible interaction with growth factors. AB - The study reports the effects of daily subcutaneous injections of the biogenic polyamines putrescine, spermidine and spermine (10 mg/kg each) given for a short postnatal period, on growth and development of rats. Polyamine treatment, while only slightly enhancing normal body weight gain, prevented the weight loss caused by surgical injury of 5-day-old animals. The treatment resulted in earlier eyelid and ear opening and in earlier maturation of righting and gripping responses. Increased number of neurons in the superior cervical ganglion that is caused by polyamine treatment, could not be prevented by castration of newborn rats, thus excluding the testes as a site through which polyamines may exert their action. An apparent increase in immunohistochemically detectable nerve growth factor was evident in iris and submaxillary salivary gland of polyamine-treated animals, but no change in epidermal growth factor immunohistochemistry was detected in the salivary gland. We conclude: (1) treatment of newborn rats with polyamines can accelerate somatic and neurobehavioral development; (2) further studies are required in order to verify and quantitate the effects of polyamines on growth factors, and (3) the results imply that exogenous polyamines may exert their growth-promoting effects on a number of cell types when these cells experience periods of polyamine dependence. PMID- 2603760 TI - Influence of GM1 gangliosides on the growth of cultured rat embryonic serotonergic neurons. AB - GM1 gangliosides were added to the medium of cultured raphe neurons enriched in the serotonergic phenotype in order to study their influence on biochemical and morphological growth parameters of serotonergic neurons. After 2 days of culture in the presence of GM1, specific uptake of serotonin measured by scintillation counting exhibited a moderate but significant increase for a GM1 concentration of 5 X 10(-8) M. Morphological parameters of 5-HT neurons were measured after immunocytochemical staining with specific serotonin antiserum, and digitalization of immunoreactive cells. Eight parameters were studied; for concentrations of 5 X 10(-8) and 10(-7) M of GM1, the absolute neuritic field area and the total length of the segments were significantly increased, whereas the number of neuritic segments, and their mean length were not modified. We conclude that GM1 ganglioside has a significant influence on the growth of serotonergic neurons. Moreover, electron microscopy showed, on treated cultures, a dramatic increase of the number of spicules all along the neuron's process, suggesting that GM1 could act by modifying the attachment of cells to their substrate. The possible molecular mechanisms of the action of GM1 are discussed. PMID- 2603761 TI - Intracranial aneurysms in India--microsurgical approach. AB - This is a retrospective study of 100 cases of intracranial aneurysms, treated in an Indian hospital, reflecting the special situation and experiences in our country. The incidence of subarachnoid haemorrhage due to ruptured aneurysm has been more or less the same as is reported from other parts of the world. The cases of recurrent haemorrhage resulting in poor clinical status are more common in our situation. Delayed referral and diagnosis were responsible for recurrent haemorrhage, increased morbidity and mortality. Forty two percent developed cerebral vasospasm within two weeks after the bleed. The use of a temporary clip on the parent vessel prevented the intraoperative rupture of the aneurysm while dissecting round about the aneurysm. Operative mortality was eight percent in the present series. PMID- 2603762 TI - Monitoring of direct cortical responses during temporary arterial occlusion at aneurysm surgery. AB - Direct cortical response (DCR) of the cerebral cortex was monitored during temporary occlusion of the feeding artery to a cerebral aneurysm in 24 patients. Animal experiments had shown that this response can be used as an index of the depth of ischaemia. In all 8 patients with middle cerebral artery occlusion and 3 out of 4 patients of bilateral A1 occlusion, the amplitude of DCR decreased, and two of them showed complete disappearance of DCR. In 10 patients with common carotid artery occlusion, only one patient showed amplitude decrease of DCR to half. These results might indicate the difference of collateral circulatory flow in each individual case. The authors suggest monitoring of DCR in temporal occlusion to be a most important practical method for ascertaining the maximal duration of temporary occlusion possible without causing infarction. PMID- 2603763 TI - Balloon test occlusion of the internal carotid artery with monitoring of compressed spectral arrays (CSAs) of electroencephalogram. AB - We used the compressed spectral arrays (CSAs) of the electroencephalogram (EEG) to monitor cerebral blood flow related events in balloon test occlusion of the internal carotid artery (balloon Matas test). Reliability of the CSAs was examined in 22 patients subjected to the test. Of 9 patients who underwent subsequent permanent carotid occlusion, in 6 there was no change on CSAs and/or in neurological conditions. In 2 patients, there was a slowing on CSAs prior to the appearance of neurological deterioration during clinical testing. CSAs transformed these EEG changes into a succinct graphic display. In 1 of the 2, for whom the Matas test was repeated 1 year later, there was a change from positive to negative and delayed cerebral infarction occurred after carotid occlusion. In the other patient, an ischemic insult occurred during the balloon occlusive procedures. The third patient had a fatal delayed ischaemic complication 3 days after surgical ligation of the cervical carotid artery, despite the negative balloon Matas test. Complications in these 3 patients were presumably related to thromboembolic mechanisms. The balloon Matas test monitored by CSAs is useful for detecting change in brain functions attributed to an inadequate blood flow. However, this test is unreliable for predicting thrombo-embolic complications. PMID- 2603764 TI - Supratentorial astrocytic tumours of childhood: a clinicopathologic study of 41 cases. AB - Forty-one patients with ages from 0 to 16 years harbouring supratentorial astrocytic tumours were treated between 1964 and 1986. Twenty-four of them were located in the cerebral hemisphere or in the ventricle, and 17 were in the basal ganglia, thalamus, and/or optico-hypothalamic region. There were nine glioblastomas multiforme, four anaplastic astrocytomas, 11 fibrillary astrocytomas, 12 pilocytic astrocytomas, two pleomorphic xanthoastrocytomas, two subependymal giant cell astrocytomas and one primitive astrocytic tumour. Low grade tumours tended to occur in young subjects near the midline, and high grade one in older patients in the hemisphere. Initial treatment in most the patients was a resection or biopsy followed by radiation therapy. Eleven patients were retreated for their recurrent tumours with combinations of surgical removal of the tumour, radiotherapy, and/or chemotherapy. After a follow-up of 3 months to 17 years, 51% of the patients survived with a median survival of 7 years. Outcome of the patients with supratentorial astrocytomas correlated mostly with the histological grade of malignancy of the tumour, and to a lesser degree with the tumour location. The biological behavior and treatment of supratentorial astrocytomas in childhood are discussed. PMID- 2603765 TI - Subarachnoid haemorrhage of unknown aetiology. AB - The authors review the literature on subarachnoid haemorrhage of unknown aetiology (SAHUE) and analyze a personal series of 212 patients diagnosed as SAHUE. These patients represent 30% of all cases of primary SAH admitted over a 14.5 year period. The age, sex, antecedents and initial clinical presentation of patients with SAHUE were indistinguishable from those of patients with subarachnoid haemorrhage due to ruptured aneurysm (SAHRA). However, the present series of SAHUE compare favourably with both a personal and a previously reported series of SAHRA insofar as clinical grade on admission (94% of patients in grades I-II of Botterell), presence of blood on CT (51%), vasospasm (5%), ischaemic deficits (3.3%), persistent hydrocephalus (3.5%), rebleeding (6%) and fatal result (3.9%) are concerned. The amount of blood on CT scan in our patients with SAHUE was associated with a significantly higher incidence of brain ischaemia and hydrocephalus but did not correlate with the Botterell grade on admission or final outcome, which were good in the majority of cases regardless of the presence or not of visible cisternal haemorrhage. The results of the present series confirm that the final prognosis of patients with primary SAH showing normal four-vessel cerebral angiography is essentially favourable. PMID- 2603766 TI - Stenosis of one carotid artery with occlusion of the contralateral carotid. AB - 23 patients with unilateral internal carotid artery stenosis (greater than 70%) and contralateral internal carotid artery occlusion in the neck are reported. The symptoms are referable to the side of the occlusion in 13 cases (57%), to the side of stenosis in 7 cases (30%) and non-localizing in 3 cases (13%). All 23 patients had a carotid endarterectomy performed on the side of the stenotic lesion. There was no operative mortality. Late neurological symptomatology after surgery was referable to the side of stenosis in 13% and to the side of occlusion in 9%. The authors consider that, in cases of significant stenosis (greater than 70%) of an internal carotid artery with a contralateral occlusion, preference should always be given to end-arterectomy of the stenotic side, reserving extra intracranial by-pass of the occluded side for patients who remain symptomatic after endarterectomy of the stenotic side. PMID- 2603767 TI - A clinical analysis of 32 brainstem haemorrhages; with special reference to surviving but severely disabled cases. AB - Thirty-two patients with CT-documented primary brainstem haemorrhage were reviewed retrospectively to obtain a clearer overall clinical picture, especially of the severely disabled survivors. They were divided into 3 groups according to outcome: eleven cases (Group 1) died within 1 month following haemorrhage, 11 cases (Group 2) survived but became bedridden, necessitating full living support, and 10 cases (Group 3) showed minimal neurological deficits and resumed normal activities. Owing to CT and improved critical care, the survival rate was 66% for the whole series. Group 2 comprised 34% of all cases. These patients were mostly alert, quadruplegic, and communicated only with great difficulty. The most common initial symptoms and CT finding in each group were as follows; Group 1: unconsciousness, respiratory disturbance, negative light reflex, tachycardia, and haematoma greater than 3.0 cm; Group 2: disturbance of consciousness, respiratory disturbance, positive light reflex, normal heart rate, and 2.0 greater than haematoma less than 3.5 cm; and Group 3: alertness or only slight disturbance of consciousness, normal respiration, positive light reflex, normal heart rate, haematoma less than 2.5 cm. Although there is an overlap among them, these findings will be useful to distinguish the three groups from each other. Patients with disturbance of consciousness, respiratory disturbance, positive light reflex, normal heart rate, and 2.0 greater than haematoma less than 3.5 cm, have a chance to survive, but in severely disabled condition, if they were treated with vigorous intensive care in the acute stage. PMID- 2603768 TI - The brain-stem and 40 Hz middle latency auditory evoked potentials in brain death. AB - Bilateral recordings of brain stem auditory evoked responses were compared with the 40 Hz middle latency auditory evoked responses in 38 patients either brain dead or in coma grade IV. In 4 cases the 40 Hz auditory evoked potential was partly preserved, while the brain stem auditory evoked potential was not reproducible beyond wave II. Recording of the 40 Hz auditory evoked potential is found to be more sensitive in some rare instances. PMID- 2603769 TI - Subpial spinal evoked potentials in patients undergoing junctional dorsal root entry zone coagulation for pain relief. AB - Seven patients with complete avulsion of the brachial plexus underwent junctional coagulation lesions of the dorsal root entry zone (DREZ) for relief of intractable pain in the paralyzed arm. Intra-operative monitoring by recording spinal cord somatosensory evoked potentials (SEP) resulting from tibial nerve stimulation was done using subpial recording electrodes situated dorsal to the posterior median sulcus at the C4 and T2 segment. SEP on the normal side showed an initial positive wave and two negative waves followed by a group of high frequency waves of relatively high amplitude which continued into high frequency, low amplitude potentials. The conduction velocity of the fastest spinal evoked potential components were, on average, 86 m/s. Recordings from the side of avulsion revealed a steep positive potential of high amplitude which appeared in five patients prior to the creation of the DREZ lesion. This effect was assumed to be secondary to spinal cord damage caused by avulsion. During the DREZ coagulation the SEP from the unaffected side did not change. On the side of DREZ coagulation the velocity of the fastest fibres decreased. Four patients reported sensory deficits after the operation, which were transient in three. In one of these patients, the first two negative potentials disappeared. In the fourth patient, who had permanent sensory deficits, the positive steep potential appeared after generation of the lesion. Our results point to the usefulness of the subpial SEPs monitoring during microneuro-surgical procedures on the spinal cord to provide further insight into evoked electrical activity of the normal and injured spinal cord, and to minimize post-operative neurological morbidity. PMID- 2603770 TI - Anterior cervical osteophytes as a cause of progressive dysphagia. AB - An uncommon cause of progressive dysphagia may be large cervical osteophytes impinging upon the cervical esophagus. Dysphagia may be due to the mechanical mass effect of a large anterior osteophyte, trapping the esophagus opposite a fixed point such as the cricoid cartilage, or a local inflammatory reaction resulting in cricopharyngeal spasm. We report three patients with progressive dysphagia due to large anterior cervical osteophytes. All three patients were treated with anterior cervical approach with removal of the osteophytes without fusion. A review of the literature in addition to the specific case histories, video fluoroscopic and radiographic findings are presented. PMID- 2603771 TI - Selective enhancement of intratumoural blood flow in malignant gliomas: experimental study in rats by intracarotid administration of adenosine or adenosine triphosphate. AB - We studied the effect of intravenous and intracarotid infusion of adenosine and adenosine triphosphate (ATP) on the regional blood flow of intracerebrally transplanted RG-C6 tumours in rats, using the hydrogen clearance method. The intracarotid administration of adenosine or ATP selectively increased blood flow in the tumour, but did not produce any significant change either in the regional cerebral blood flow of the extratumoural ipsilateral hemisphere or in the ipsilateral hemisphere without tumour. The intracarotid administration of ATP at a dose of 10 micrograms/kg/min produced the most effective increase in the tumour blood flow (+51.5 +/- 16.8%). In contrast, both the intravenous administration of adenosine and that of ATP failed to increase tumour blood flow. These results may possibly indicate that intracarotid administration of the adenosine or ATP might contribute in selectively enhancing the delivery of anti-cancer agents to malignant brain tumours. PMID- 2603772 TI - Cerebral autoregulation following prophylactic and delayed experimental STA-MCA bypass. AB - Cerebral autoregulation is impaired in ischaemic regions. We hypothesized that pre-existing STA-MCA bypass would be superior to delayed revascularization in maintaining ipsilateral rCBF and preserving cerebral autoregulation following experimental stroke. Two series of dogs were tested to evaluate this hypothesis, but which was disproved for the chosen experimental conditions. In the first, eight dogs underwent craniotomy, STA-MCA bypass, and radiolabeled microsphere rCBF determinations. Blood pressure was manipulated with intravenous adenosine and levarterenol. Ischaemic zone rCBF was measured at MAP 60 mm Hg (97.2 ml.min 1.100 g-1) and MAP 140 mm Hg (113.6) (p = NS), in the intact arterial system with the patent bypass in place. An hemispheric ipsilateral ischaemic lesion was then created, and three further microsphere rCBF determinations were made at MAP 60 mm Hg (41.7 ml.min-1.100 g-1), MAP 100 mm Hg (52.6) and MAP 140 mm Hg (58.3). There were no significant differences between these measurements (ANOVA p = NS). In a second series of five animals the bypass was placed and the stroke lesion created first. Ischaemic zone rCBF was then measured at MAP 60 mm Hg (35 ml.min-1 . 100 g 1) and MAP 140 mm Hg (44 ml.min-1 . 100g-1) (p = NS), with the patent bypass in place. The bypass was then clamped for 15 minutes and profound ischaemia confirmed (5 ml.min-1 . 100 g-1, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2603773 TI - Intolerable pulse-synchronous tinnitus caused by occlusion of the contralateral common carotid artery. A successful treatment by aorto-carotid bypass surgery. AB - A case with severe pulsatile tinnitus of the left side caused by occlusion of the right common carotid artery was reported. Tinnitus in this case was supposed to be due to the rich blood flow of the external carotid systems developed as collateral routes resulting from the occlusion of the right common carotid artery. It subsided with the establishment of a bypass using a vein graft between the ascending aorta and the residual patent portion of the right common carotid artery. PMID- 2603775 TI - Per- and postoperative changes in the arterio-venous oxygen content difference (AVDO2) in patients subjected to craniotomy for cerebral tumours. AB - Sixteen patients with supratentorial cerebral tumours were subjected to craniotomy under thiopentone, fentanyl, nitrous oxide, halothane anaesthesia during moderate hypocapnia (PaCO2 level 4.0 kPa). The arterio-venous oxygen content difference (AVDO2) was measured peroperatively, and repeatedly during the first three hours after extubation. Peroperatively the level of AVDO2 averaged 8.0 vol% during opening of the dura, and decreased to 7.0 vol% during closure of the dura (P less than 0.05). Immediately after extubation the AVDO2 decreased to 4.3 vol% (P less than 0.05), and during the next 3 hours a gradual increase to 5.8 vol% (P less than 0.05) was disclosed. In individual cases the postoperative changes in AVDO2 correlated fairly well with changes in mean arterial blood pressure (MABP), but other factors including duration of the operation, age of the patients, size of the tumour, level of PaCO2 and adaptation to prolonged hyperventilation during operation are supposed to be responsible for the low levels of AVDO2 observed in the postoperative period. PMID- 2603774 TI - Long-term survival after removal of primary intracranial malignant melanoma. Case report. AB - A 57-year-old male with primary intracranial malignant melanoma who survived 9 years and 6 months is reported. He underwent surgical removal of the tumour three times during the decade 1978 to 1988, and received chemo-immuno-radiotherapy during that time. Acute tumour growth, suggesting tumour dissemination, was seen in the CT scans after the third removal of recurrent tumour, but then it disappeared after combined chemoradiotherapy with DTIC. He gradually became inactive, probably because of brain atrophy caused by high-dose radiotherapy and chemotherapy, and died of renal failure without any sign of recurrence on CT scans. PMID- 2603776 TI - Meeting on mitochondrial pathology in neuromuscular diseases. Naples, January 26, 1989. Proceedings. PMID- 2603777 TI - Mitochondrial myopathies: morphological and biochemical studies in human muscle cultures. AB - The mitochondrial myopathies are a heterogeneous group of disorders presumed to be caused by primary mitochondrial dysfunction with impairment of energy provision from oxidative metabolism. An increasing number of specific functional mitochondrial deficiencies have been documented and recently new strategies are beginning to analyze molecular and genetic mechanisms. Nevertheless these specific disorders have not been studied extensively in human muscle cultures. The objectives of our study were to reproduce morphological and biochemical changes in cultured myotubes of three Kearns-Sayre syndrome (KSS) patients to evidentiate a different mitochondrial susceptibility to 2-4 dinitrophenol (DNP) into normal and KSS muscle cultures, and to investigate the protective effect of ubidecarenone (Q10) on KSS myotubes exposed to DNP. In KSS cultures as compared to normal ones no abnormalities in growth pattern and differentiation were observed. KSS myotubes DNP exposed showed some abnormally large mitochondria with parallel-packed cristae and decrement in all mitochondrial enzymes activity ranging from 20 to 40%. In normal myotubes DNP exposed and in patient cultures DNP-Q10 treated a normal mitochondrial morphology and a recovery of enzymatic activity was found. In Complex I deficiency patient cultured myotubes cytochemical, immunocytochemical, ultrastructural and biochemical studies were performed and no abnormalities were found. Negative tissue culture findings could be explained by the fact that the defect cannot be reproduced in aneural cultures, and that there could be a gradual selection of cells containing a preponderance of wild type mitochondria over those that contain mutant mitochondria. PMID- 2603778 TI - Mitochondrial encephalomyopathies. PMID- 2603779 TI - [Alterations of mitochondria in metabolic diseases. Carnitine deficiency, carnitine palmitoyltransferase deficiency and beta oxidation]. AB - Recently a number of defects of fatty acid transport and beta-oxidation have been described. Primary carnitine deficiency presents itself as muscle carnitine deficiency, systemic carnitine deficiency or a cardiomyopathic subtype. Another abnormality of fatty acid transport is due to inner carnitine palmitoyl transferase deficiency, usually associated with a myoglobinuric phenotype. Long chain, medium and short chain acyl-CoA-dehydrogenase defects are usually associated to Reye's syndrome, encephalopathy, organic aciduria and secondary carnitine deficiency. PMID- 2603780 TI - [Muscle weakness and intolerance to exercise in mitochondrial myopathies]. AB - Muscle weakness and intolerance to exercise are two of the main features commonly shown by patients affected by mitochondrial myopathies. In order to obtain an objective and quantitative evaluation of muscle weakness and endurance, we studied an evaluation protocol devoted to the assessment of 1) muscle strength by the isokinetic ergometer and 2) the metabolic aspects of exercise by means of Maximal Oxygen Consumption and endurance by a Steady State Submaximal exercise evaluation. The protocol has been applied to the study of patients affected by mitochondrial diseases and proved to be a reliable method to quantitate the defect in the oxidation pathways, either before or during the therapeutic follow up. PMID- 2603781 TI - Hearing loss associated with progressive ataxia (Lichtenstein-Knorr disease?). Report of a sporadic case with peculiar neuroradiological findings. AB - A sporadic case of hearing loss with ataxia, clinically suggesting Lichtenstein Knorr disease, is described. Magnetic Resonance (MR) shows an involvement of the white matter, which appears diffusely reduced and abnormal, together with a peculiar tickening of the grey matter. The possible relationships with leukodystrophies and with generalized cortical dysplasias are discussed. To our knowledge, MR imaging has never been performed in Lichtenstein-Knorr disease. PMID- 2603782 TI - Fahr's disease in postthyroidectomy hypoparathyroidism. A case report. AB - The onset of Fahr's disease in a patient with postoperative hypoparathyroidism is described. The genesis of this rare pathological occurrence could be ascribed, in our opinion, to the combined action of "local" (precedent encephalic circulation disorders) and "general" factors (Ca and P metabolism disorders following postoperative hypoparathyroidism). PMID- 2603783 TI - Kinins V. Part A. Proceedings of the Fifth International Kinin Congress. November 20-December 3, 1987, Tokyo, Japan. PMID- 2603784 TI - The role of T-kininogen and H and L kininogens in health and disease. PMID- 2603786 TI - The kallikrein-kinin system in inflammation. PMID- 2603785 TI - Recent studies on the rule of kinins in inflammatory diseases of human airways. PMID- 2603787 TI - A significant role of plasma kallikrein-kinin system in plasma exudation of rat carrageenin-induced pleurisy. PMID- 2603788 TI - Kininogen in tumor-bearing mice. PMID- 2603789 TI - Role of cardiovascular phospholipase A2 and C in the development of DOCA-salt hypertensive rats. PMID- 2603790 TI - Neutrophil producing capacity of 5-lipoxygenase metabolites of arachidonic acid after major surgery. AB - It is well known that patients who undergo surgical operations have a high risk of infection and sepsis. One explanation for this high risk may be a depression of neutrophil functions at the postoperative period. In the present study, the effects of surgical stresses on neutrophil functions were studied in ten patients who underwent general anesthesia and major surgery. The neutrophil functions especially focused on were the producing capacities of 5-lipoxygenase metabolites of arachidonic acid such as Leukotriene B4 (LTB4), LTC4, LTD4, 6-trans-LTB4, and w-oxidation products of LTB4. Neutrophils were stimulated with calcium-ionophore A23187 (2x10(-5) M) in the presence of arachidonic acid (5x10(-5) M) for 5 minutes at 37 degrees C. The arachidonic acid metabolites were extracted by methanol. After centrifugation, the supernatant of the mixture was concentrated and applied to a C-18 column on reversed phase high performance liquid chromatography (RP-HPLC) system, monitoring the absorbance at 280 nm. In all cases, the LTB4 production significantly increased postoperatively with an increment of 6-trans-LTB4 and w-oxidation products of LTB4. The LTC4 production, by contrast, significantly decreased postoperatively. LTD4 production was observed at neither pre nor postoperative periods. The total amount of LTA4 metabolites at the postoperative period, including LTB4, LTC4, and 6-trans-LTB4, increased 1.2 times compared with that at preoperative period. This indicates the possibility of the alteration of the neutrophil metabolism in 5-lipoxygenase cascade, the increment of LTA4 generation and the change of LTA4 metabolism from LTC4 synthesis to LTB4 generating pathway. PMID- 2603791 TI - The effect of bradykinin and its fragments on the arachidonate cascade of brain microvessels. AB - The lipoxygenase pathway dominated the arachidonate cascade in the microvessels isolated from cerebral cortical microvessels of male rats. Bradykinin significantly reduced the lipoxygenase pathway and the synthesis of PGD2 in the microvessels of rats. The synthesis of vasoconstrictor cyclooxygenase metabolites was stimulated with Ser-Pro-Phe-Arg tetrapeptide in the cerebral capillaries while the Phe-Arg dipeptide stimulated the release of arachidonate metabolites. The arachidonate cascade was shifted to the cyclooxygenase pathway with angiotensin III in cerebral microvessels. Kallikrein stimulated the lipoxygenase pathway and the synthesis of vasoconstrictor cyclooxygenase metabolites. PMID- 2603792 TI - Mechanism of bradykinin-induced nociceptive response. PMID- 2603793 TI - Antagonism of the algesic action of bradykinin on the human blister base. AB - The effect of bradykinin (BK) and some analogues of BK on the human blister base was studied. BK produced reproducible dose-related increases in pain responses. A characteristic delay, which was not dose-related occurred between application of BK and the resultant response. The rank order of potency of several kinin analogues on the pain response was BK much much greater than sigma-cyclo-(Lys1 Gly6)-BK = sigma-cyclo-kallidin greater than des-Arg9-BK. No increase in pain response was seen with repeated application of the selective B1-receptor agonist des-Arg9-BK to the same blister base at 4h intervals. The B1 receptor antagonist des-Arg9-Leu8-BK was without effect against BK-induced responses. The B2-receptor antagonists, D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg-TFA and D-Pro-Phe-Arg heptylamide produced significant antagonism of the bradykinin-induced pain responses at doses which had no effect against 5-hydroxytryptamine or potassium chloride. It is concluded that the kinin receptor mediating pain on the human blister base is of the B2 type. PMID- 2603794 TI - Effects of sodium intake on urinary excretion and renal content of bradykinin and its metabolites in rats. PMID- 2603795 TI - Kallikrein release by rat kidney slices: effect of norepinephrine. PMID- 2603796 TI - Isolation and study of the properties of kininase from the venom of spider Latrodectus tredecimguttatus. PMID- 2603797 TI - Post synthetic modification of CK-MM by kininase I. PMID- 2603798 TI - Structure of human carboxypeptidase N (kininase I). PMID- 2603799 TI - Rocket immunoassay of high and low molecular weight kininogens in human plasma. AB - High molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK) in human plasma could be rapidly (36 min.) separated on a DEAE-Sepharose Fast Flow column (1.0 x 5 cm and 0.50 ml plasma) by applying a NaCl step gradient. Quantification was then carried out by the Laurell rocket method with an antiserum raised against HMWK. Standard preparations for the assays were (I) crude HMWK and (II) crude LMWK prepared by the one-step procedure mentioned. In disc PAGE (8% with 0.1% SDS) immunoblot showed two main bands in I, migrating to apparent mol.wts. of 180,000 and 120,000. The 180,000 band predominated in native plasma. Purified HMWK (spec.act. 14 micrograms bradykinin/A 280) yielded in addition a band corresponding to a mol.wt. of 100,000. Immunoblot of II showed one broad zone over the mol.wt. range 65-70,000. The average assay values obtained in human plasma specimens from 10 males were 85 micrograms/ml for HMWK (range 65-130) and 174 micrograms/ml for LMWK (range 164-183). HMWK occasionally lost immunoreactivity during purification without a corresponding loss of kinin. Such a loss of immunoreactivity seemed to run parallel with a reduced release of kinin induced by hog pancreas kallikrein. PMID- 2603800 TI - High molecular weight kininogen binds to neutrophils. PMID- 2603801 TI - Inhibition of thrombin-induced platelet aggregation by high molecular weight kininogen. PMID- 2603802 TI - Characterization of kinins released from human kininogens by human urinary kallikrein. PMID- 2603803 TI - Ornitho-kininogen and ornitho-kinin: isolation, characterization and chemical structure. AB - Ornitho-kininogen was purified from chicken and duck blood plasmas by a two-stage method using chromatography on columns of S-alkylated papain-Cellulofine and DEAE 5PW. The isolated preparation from chicken plasma gave a single band on SDS-PAGE with or without 2-mercaptoethanol and on disc-PAGE. The molecular weight of ornitho-kininogen was estimated as 74,000 on SDS-PAGE using the Ferguson plot method. Ornitho-kininogen was found to have the similar properties to those of mammalian high molecular weight kininogen (HMWK), in terms of the amino acid composition, molecular weight, and susceptibility to plasma kallikrein. No kininogen corresponding to mammalian low molecular weight kininogen (LMWK) and rat T-kininogen could be detected in chicken plasma. In fact, ornitho-kininogen was degraded rapidly by bovine plasma kallikrein, liberating a kinin. This kinin was isolated from the digest by reversed-phase HPLC. The primary structure of the isolated kinin was determined as Arg-Pro-Pro-Gly-Phe-Thr-Pro-Leu-Arg. The sequence of this peptide, named ornitho-kinin, was similar to that of bradykinin except for the substitution of Thr-6 and Leu-8 for Ser-6 and Phe-8. The isolated ornitho-kinin induced a contraction of chicken smooth muscle and had a strong hypotensive effect in the chicken. However, it did not contract the isolated rat uterus. It is suggested that this specificity difference is due to the replacement of Phe-8 by Leu-8. The sequence of residues 1-30 of ornitho-kininogen exhibited 43% identity with that of bovine kininogen. PMID- 2603804 TI - The kallikrein-kininogen system in myocardial infarction. PMID- 2603805 TI - The pathophysiological role of kinin and chemical mediators on experimental allergic rhinitis. AB - In order to clarify the pathophysiological role of the chemical mediators, the releases of kinins, histamine and leukotriene C4(LTC4) into the nasal cavity were measured following nasal allergic challenge in ovalbumin(OA)-sensitized guinea pigs, or following nasal stimulation with one of these chemical mediators in OA non-sensitized animals. In sensitized animals, an increased vascular permeability of nasal mucosa was recognized immediately after antigenic stimulation and lasted for 60-90 minutes. Releases of kinins and LTC4 into the nasal lavage fluid augmented not only immediately after the antigenic challenge, but also during 60 to 90 minutes after the stimulation. Release of histamine into the nasal lavage fluid was observed only immediately after the antigenic stimulation. In non sensitized guinea pigs, nasal stimulation with bradykinin accelerated nasal vascular permeability. Nasal stimulation with histamine or LTC4 resulted in increase of nasal vascular permeability and of kinins concentration in the nasal lavage fluid. These results suggest that kinins might be concerned with the immediate and later vascular permeability during the allergic response. PMID- 2603806 TI - Kallikrein activity in saliva of patients with inflammatory and hyperplastic diseases of the oral mucous membrane. PMID- 2603808 TI - The influence of Oxindanac on kallikrein metabolism. PMID- 2603807 TI - The effect of cyclosporine on urinary kallikrein excretion in patients with rheumatoid arthritis. AB - The effect of cyclosporine (6 to 8 mg/kg/24 hr) on urinary kallikrein excretion is summarized for 9 patients with rheumatoid arthritis using a specific kallikrein radioimmunoassay. Baseline serum creatinine and BUN values were within the normal range for all patients, and baseline kallikrein excretion rates were either normal (n = 5) or more than two S.D. below the mean of the normal group (n = 4). The patients with normal baseline values excreted significantly less urinary kallikrein three and six months after cyclosporine therapy was started, but all of them completed the six-month protocol. Patients in the subgroup with low baseline values also decreased their kallikrein excretion in response to cyclosporine therapy, and two of the four in this group experienced elevations of BUN such that therapy was terminated. In a low-dose (3 mg/kg/24 hr) open extension that followed the initial trial, kallikrein excretion decreased by almost 50% at least one month before any change in serum creatinine was observed. The data suggest that changes in urinary kallikrein excretion rates may be an indicator or predictor of cyclosporine nephrotoxicity. Decreased kallikrein excretion rates could also be a factor in the diminished renal blood flow reported in patients treated with cyclosporine. PMID- 2603809 TI - The effect of a bradykinin antagonist on vasodilatation in the cat and rabbit. PMID- 2603810 TI - Effects on blood pressure of intracerebroventricular administration of a kinin antagonist. AB - The components of the kallikrein kinin system are present in brain, and blood pressure is increased when kinins are injected into the brain cerebral ventricles. Therefore, brain kinins may play a role in the regulation of blood pressure. Kinin analogs which are effective as blockers of the vasodilatory and musculotropic activity of kinins have recently become available. Our objective in this study was to examine whether one of these kinin antagonists (K-ant) inhibits the pressor activity of intracerebroventricular (ICV) bradykinin, and whether ICV injections of this antagonist would alter basal mean blood pressure (BP). The analog used was DArg0-Hyp3-Thi5,8-DPhe7-bradykinin. All injections (10 microliters) were made into a lateral cerebral ventricle of restrained, conscious rats. The hypertensive response to 0.5 microgram bradykinin was partially blocked by simultaneous injections of either 5 or 10 micrograms of the K-ant: From (delta MBP = 36 +/- 7 to 17 +/- 5, p less than 0.05, and from 34 +/- 6 to 8 +/- 1 mmHg, p less than 0.01, respectively. Lower concentrations of K-ant were ineffective; the K-ant at doses up to 10 micrograms had no effect on BP. Doses of 25 and 50 micrograms increased BP (delta MBP = 32.5 +/- 5 and 59.0 +/- 5.5 mmHg, respectively, p less than 0.001). Both the 25 and the 50 micrograms doses of the K-ant induced barrel rotation in all rats. These data suggest that kinins present in circumventricular structures do not play a role in normal blood pressure regulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2603811 TI - Hageman factor dependent kinin generation system in guinea pig skin: extravascular localization of the components, and prolonged vascular reaction in inhibitor-depleted animal of this system. AB - 1. Monospecific antibodies against components of the guinea pig Hageman factor dependent system, such as Hageman factor, prekallikrein and high-molecular-weight (HMW) kininogen were prepared. These antibodies demonstrated the presence of all of these components in the normal guinea pig skin extract with the properties identical to them in plasma on western immunoblotting analysis. 2. Guinea pig macroalbumin which is a major circulating inhibitor of activated Hageman factor was immunologically depleted from three animals. Duration of a vascular permeability reaction caused by an intradermal injection of activated Hageman factor was prolonged in all of these guinea pigs approximately twice as long as the control, indicating a presence of negative feedback regulation of the Hageman factor-dependent kinin generation cascade in dermal tissue via the circulating protease inhibitor. PMID- 2603812 TI - Some cardiovascular and hematological changes induced in the rat by activation of Hageman factor with ellagic acid. PMID- 2603813 TI - Isolation and characterization of plant inhibitors directed against plasma kallikrein and factor XII. PMID- 2603814 TI - Changes in components of the KK-system after recirculation and the addition of plasma kallikrein. PMID- 2603815 TI - Kinin release from human LMW-kininogen by the cooperative action of human plasma kallikrein and leukocyte elastase. PMID- 2603816 TI - Human urinary prokallikrein--structural analysis on activation mechanism. AB - The complete amino acid sequence of human urinary kallikrein has been determined. The enzyme was a single polypeptide which comprised 238 amino acid residues. In the case of prokallikrein, a propeptide which was consisted of seven amino acid residues was attached to N-terminal isoleucine of kallikrein. The sequence of Asn X-Thr(Ser), common to glycosylation site, was identified at positions 78-80, 84 86 and 141-143. It has been shown from the sequence of kallikrein that Arg(-1) Ile(1) and Arg(87)-Gln(88) bonds are hydrolyzed with trypsin on rapid activation of prokallikrein and the formation of disulfide-linked two chain kallikrein. PMID- 2603817 TI - Human urinary kallikrein: amino acid sequence and carbohydrate attachment sites. PMID- 2603818 TI - Structural analysis of ASN-linked oligosaccharides of porcine pancreatic kallikrein. PMID- 2603819 TI - Fast atom bombardment mass spectrometry (FAB-MS): analysis of complex carbohydrate chains of tissue kallikreins. AB - Molecular ions and fragment ions of underivatized and permethylated oligosaccharides derived from human urinary kallikrein and some model glycoproteins gave information about the sugar composition and arrangement of sugars. These ions were conveniently created by FAB-MS in a JEOL JMS-HX110 high field high resolution mass spectrometer. Glycoprotein samples were digested with N-glycanase and the asparagine(Asn)-linked oligosaccharides were separated from polypeptides by Sephadex G-50 chromatography. The mixture of oligosaccharides was converted to the reduced p-aminobenzoic ethyl ester (ABEE) derivative and the components separated by HPLC on an ion-exchange (AX-10) column. Individual components were analyzed by negative FAB-MS using glycerol as a matrix. Permethylated oligosaccharides were also analyzed by positive FAB-MS. PMID- 2603820 TI - Isolation of [hydroxyproline3]Lysyl-bradykinin formed by kallikrein from human plasma protein. AB - [Hydroxyproline3]Lysyl-bradykinin ([Hyp3]Lys-BK), a new kinin was isolated, besides Lysyl-bradykinin (Lys-BK), from the reaction mixture of human plasma protein Cohn's fraction IV-4 with hog pancreatic kallikrein. The liberated kinins were isolated by procedures including ethanol extraction, Sephadex G-15, CM cellulose and reverse-phase high performance liquid chromatography and quantitated by radioimmunoassay. On HPLC, two peaks of immunoreactive kinins emerged. Peak 1, an unknown kinin proceeded to peak 2 which had an identical retention time to that of Lys-BK. The amino acid sequence of the unknown peak 1 proved to be Lys-Arg-Pro-Hyp-Gly-Phe-Ser-Pro-Phe-Arg, or [Hydroxyproline3]Lys-BK, and peak 2 Lys-BK. The ratio of the amounts of two kinins thus formed were [Hyp3]Lys-BK 25 +/- 4% and Lys-BK 75 +/- 4%. The existence of [Hyp3]Lys-BK suggests a presence of a new kininogen containing [Hyp3]Lys-BK in human plasma protein. PMID- 2603821 TI - A micro-kininogenase assay for studies of kallikrein in renal micropuncture/microperfusion. AB - We report the development of a micro-kininogenase assay suitable in studying the dynamics of kallikrein at intranephron segmental level. The detection limit is 119 fg or 2.6 attomoles of kallikrein. Activation of microquantities of kallikrein is possible with the use of Triton X-100. Because of its extremely high sensitivity and reproducibility the assay is likely to also prove useful in physiological studies in which only very small amounts of kallikrein containing samples can be obtained. PMID- 2603822 TI - Exercise-induced increase in glandular kallikrein activity in human plasma and its significance in peripheral glucose metabolism. PMID- 2603823 TI - Kallikrein-induced rat uterus contraction is dependent on kinin release. PMID- 2603824 TI - Relationship between human seminal kallikrein-kinin system and spermatogenesis. AB - The concentration of kallikrein and the activity of angiotensin converting enzyme (ACE) in the semen specimens mainly from patients with male sterility and from those who were subjected to vasoligation, and in the prostatic fluid specimens from normal controls were determined by radioimmunoassay (RIA) and the modified Cushman's method, respectively. The kallikrein level in the semen from normal control was 40.4 +/- 21.3 ng/ml which was more than 10 times that in the blood. The value tended to increase with the decrease of the number of sperm. But there was no significant correlation between the kallikrein level and the sperm motility. The seminal kallikrein level from the patients subjected to vasoligation and that in the prostatic fluid from the normal male were 20-28 ng/ml. Therefore, that amount was considered to be secreted from the prostate gland. The results of column chromatography suggested that kallikrein combined with the other substances to form a high molecular compound in the semen. The ACE activity was 94.9 +/- 10.9 nmol/ml/min in the semen from the normal control, which was about three times that in the blood. Similar to kallikrein, it tended to decrease with the increase of the number of vasoligation and that in the prostatic fluid from the normal males was higher than that in the semen from the normal control and patients with male sterility, it was estimated that the considerable amount of ACE was secreted from the prostate gland. PMID- 2603825 TI - Studies on kallikrein-kinin system and enzymes activity in organs and urine from diabetic mice models. PMID- 2603826 TI - Dose-dependent effects of bradykinin infusion in postoperative patients. PMID- 2603827 TI - Evidence for multiple functions of T-lymphocytes associated serine proteinases. PMID- 2603828 TI - Interrelationship between urinary kallikrein and arginine-vasopressin in man. AB - Physiological saline solution was infused in 9 normal subjects and 6 patients with central diabetes insipidus (DI). At 120 min after the start of infusion, arginine vasopressin (AVP) was injected (i.m.). Urine was collected every 30 min fraction. The urinary excretion of kallikrein-like activity (KAL-A) (S-2266 hydrolysis activity) was significantly lower in patients with DI than in normal subjects, without showing the differences of plasma renin activity (PRA), plasma aldosterone concentration (PAC), creatinine clearance (Ccr) and blood pressure between the two groups, except a marked water-diuresis in DI. The urinary excretion of KAL-A correlated positively with the urinary excretion of AVP. AVP administration significantly increased the urinary excretion of KAL-A. After overnight fasting, an acute oral water-loading was carried out for 15 min in 6 normal subjects. Concomitant with a significant suppression of the level of plasma AVP from the first 30 min, a slight, but significant, decrease in urinary excretion of KAL-A was observed in the first 30 min fraction after loading, compared with the control period. Afterwards, the urinary excretion of KAL-A increased prominently with an increase in urine flow. KAL-A in the urine decreased promptly from the first 30 min fraction and then gradually until 120 min after loading. Urine volume and free-water markedly increased except the first 30 min fraction, compared with the control period. Thus it is suggested that AVP is one of factors which actually regulate the secretion of renal kallikrein in man. PMID- 2603829 TI - Effects of kinin on electrolytes transport and regulation of kininase activity in distal nephron segments of the rat. PMID- 2603830 TI - [The physical development of infants and young children. 6. Skinfold thickness--a longitudinal study]. AB - As a further result of a longitudinal study (conducted from 1979-1982) the somatic development figures for the skinfold thickness of 84 male and 91 female children from birth up to three years are presented. The Lange caliper was used to perform the measurements according to the recommendations of the International Biological Programme (8 sites of measurement on the right side of the body). The results for the development of skinfold thickness are similar to those of the Dortmund Study (1974), but in part quite different compared with earlier longitudinal studies (1956): our own investigations show a greater skinfold thickness during the first three months of life and thereafter lower figures up to the age of 18 months. The results are recommended by the authors as reference figures for the G.D.R. PMID- 2603831 TI - [Body height, body weight and the Quetelet-Kaup Index in students 13 to 16 years of age in a rural district]. AB - The influence of excessive body weight on cardiovascular disorders and mortality has been demonstrated for adults. The prognosis for extreme obesity is also unfavourable for young people. However, there is still a considerable lack of clarity about the predictions to be based on slight or moderate obesity in childhood and adolescence. The results of the measurement of the height and body weight of 1,252 pupils of between 13 and 16 years in an rural district, together with the calculations of the Quetelet Kaup index, are set out here. Over this age rang the Quetelet Kaup index increased from 18.8 kg/m2 to 20.6 kg/m2 for the boys and from 19.5 kg/m2 to 21.3 kg/m2 for the girls. There is a discussion of the connections between relative body weight and sexual maturity. PMID- 2603832 TI - [An instrument for measuring skinfold thickness. A short report]. AB - The paper describes a new skinfold caliper for body fat evaluation. The operating pressure of the instrument is 10 p/mm2. Results are displayed on a dial. PMID- 2603833 TI - [Caries morbidity in infants and preschool children with reference to social factors of influence]. AB - The caries frequency of 653 children between 2-4 years of age was followed up over 2 years. Only very few of two year old children showed a relative high incidence of caries. Among the 4 year old children the incidence of caries was particularly high. Caries is more prevalent among children who stay at home than among those attending creches. The difference is due to the absence or irregular use of fluoride tablets, to inadequate cleaning of teeth and a high consumption of sweets in the families. Pre-school children without siblings, and those whose parents are working in shifts, should more often undergo stomatological supervision because of their greater risk suspectibility to caries. PMID- 2603834 TI - [Accidents in children in relation to the accident site, age and sex]. AB - An analysis was conducted of 1,064 child accident in-patients in the county of Suhl in 1983 and of 884 child accident out-patients in the district of Schmalkalden from July 14th, 1984 to July 13th 1985. The children were 1 to 15 years old. The analysis of the sites of the accidents was carried out with regard to age and sex. Conclusions about accident prevention were drawn from the analysis. PMID- 2603835 TI - [Comparative presentation of illness-induced absenteeism of nursery and kindergarten children in a rural district]. AB - The absence morbidity was registered for one year in 36 day nurseries and 44 kindergartens. The 25%, 50%, and 75% percentiles for morbidity in these institutions were compared from various points of view. An attempt was made to describe the role of external environmental factors in pre-school institutions for the children's state of health. PMID- 2603836 TI - [Current status of sex education of preschool children]. AB - The quantity of empirical data on contents and sources of sexual knowledge and sex-typical attitudes at preschool children is out of all proportion to the importance of this age for the formation of sexual behaviour and the establishment of relations between the sexes in family and society in the course of ontogenesis. The results of standardized interviews of 190 boys and 176 girls aged four to seven years at urban and rural nursery schools on their sexual knowledge and on their ideas of properties, roles and functions of the sexes (sex role ideas) will help fill this gap. Compared to previous retrospective studies on elder children and adolescents, sexual knowledge has become more wide-spread and correct and increasingly comes from the desired sources of information. The emotional and educational factors involved in impairing the information, however, are not yet sufficiently developed and the incidence of attitudes promoting an equal cooperation between the sexes is rather limited. The necessity of enabling the educators for sexual education is again emphasized. PMID- 2603837 TI - [Indoor climatic conditions of the floor zone in child nurseries]. AB - The room climatic conditions in the near floor zone were measured in creches. The surface temperature of the floor during the heating season did not reach the desired range of 20 to 22 degrees C. 59% of the measured minimal values, 39% of the mean values, and 18% of the maximal ones were about 15 degrees C or even drastically lower. Of the air temperature in the near floor zone (at a level between 0.15 m and 0.50m) 31% of their minimal values at the level of 0.15 m and 27% of their minimal values at the level of 0.50 m values were below 16 degrees C. The investigations of the vertical temperature gradients during the heating season showed that only 9% of the values measured between 0.50 m and 1.50 m meet the required standard of 1 degree C temperature difference per meter. Conclusions are drawn and discussed. PMID- 2603838 TI - Outcome of falls in women: endogenous factors associated with fracture. AB - Thirty-six women who had sustained soft-tissue injury after a simple fall were compared with age-matched controls who had suffered a fracture in a similar fall. Subjects aged 45-70 years who had suffered a fracture had significantly lower bone density in the proximal femur and lower grip strength than their controls. No differences in femoral bone density or grip strength were found between the two groups at ages over 70, but the women with fractures were on average of greater body weight than the no-fracture group. Bone mineral density declined more rapidly with age and was less closely correlated with body weight and time since menopause in the no-fracture group than among the women with a fracture. We conclude that the determinants of fracture vary with age; low bone density and low muscle strength are associated with fracture below the age of 70 but not at higher ages. PMID- 2603839 TI - A prospective study of elderly general surgical patients: I. Pre-operative medical problems. AB - A prospective study has been carried out on 288 general surgical patients aged 65 years and over. The present report looks at pre-operative patient characteristics. A high rate of pre-operative morbidity was found, with only one patient in five having no pre-operative medical problem. Evidence of respiratory disease was found in 29%, 14% gave a history of previous congestive heart failure, 9% had symptoms of angina, 5% had had strokes in the past, and 9% had an impaired mental score. In 30% of patients, three or more pre-operative medical problems were detected. When compared with those aged 65-74 years, patients aged 75 years and over were more likely to be admitted non-electively, had significantly more cardiovascular signs and poorer mental scores. When compared with elective admissions, patients admitted non-electively were older, had more clinical and radiological signs of respiratory disease and lower mental scores. The findings of the present study have been compared with previous reports of elderly surgical patients. PMID- 2603840 TI - A prospective study of elderly general surgical patients: II. Post-operative complications. AB - A prospective study was carried out on 288 general surgical patients aged 65 years and over. Over 40% of patients suffered no post-operative complication. The commonest post-operative problem was respiratory, with 17% of patients having simple atelectasis, 12% acute bronchitis and 10% pneumonia. Six per cent of patients developed post-operative heart failure and/or myocardial infarction. Delirium was noted post-operatively in 7% of patients, and new focal neurological signs in 1%. The post-operative hospital fatality rate was 5% (4% when deaths due to carcinomatosis were excluded). Nine patients out of ten spent less than a month in hospital. The relation of post-operative morbidity and mortality to seven factors was examined: type of surgery, urgency of surgery, urgency of admission, age, number of pre-operative medical diagnoses, American Society of Anesthetists' grade, and pre-operative mobility level. It appears that pre operative medical fitness rather than chronological age is the main determinant of post-operative outcome in the elderly surgical patient. PMID- 2603841 TI - Factors affecting walking speed of elderly people. AB - Associations between walking speed and other variables have been investigated in a group of 67 women and 58 men aged between 65 and 90 years and living independently. In men, walking speed was related positively to calf strength, step-score (a measure of customary physical activity), hours spent in active leisure, height and weight, and negatively to age and the presence of health problems. In women, the relations were the same, with the exception of weight, and reported leg pain was negatively associated with walking speed. Multiple regression analysis showed that in men 44% of the variance in walking speed was accounted for by height, calf strength and the presence of health problems, and that in women 42% of the variance was accounted for by height, calf strength, step-score and the presence of leg pain limiting mobility. The significance of these findings to maintenance and improvement of walking speed in the elderly is discussed. PMID- 2603842 TI - Calcification on chest radiographs: the association with age. AB - Seven hundred chest radiographs taken in a general hospital were reviewed, 100 (50 men and 50 women) from each of seven decades (3rd to 9th). Each radiograph was examined to determine the site and extent of calcific changes. Prevalence of costal cartilage calcification increased from 6% in the 3rd decade to 45% in the 9th and was commoner in men. Aortic calcification was absent below age 50 and increased from 4% in the 6th decade to 57% in the 9th. Both these trends were statistically significant. Other sites of calcification were found only in patients aged over 70; these included pleural, pericardial, tracheal, myocardial and diaphragmatic calcification. PMID- 2603843 TI - Assessment of inter-rater reliability. PMID- 2603844 TI - Clostridium difficile in elderly patients. PMID- 2603845 TI - [Retinal circulation in rhegmatogenous retinal detachment demonstrated by videofluorescence angiography and image analysis. I. The condition of retinal circulation before retinal detachment surgery]. AB - The retinal circulation in cases of retinal detachment was studied in eight eyes with rhegmatogenous retinal detachment. Retinal mean circulation times of the detachment areas and the non-detachment areas were measured by a system using videofluorescence angiography and image analysis with dye dilution technique. The mean circulation times were 4.05 +/- 1.13 seconds (mean +/- standard deviation) in the non-detachment areas and 6.59 +/- 2.91 seconds in the detachment areas. The difference between the two areas was statistically significant (p less than 0.03). The results demonstrated that the velocity of retinal circulation is slower in retinal detachment area. PMID- 2603846 TI - [Inter-individual variability of mean latencies in the dynamic topography of short latency visual evoked potentials and the origin of brainstem potentials evaluated by the dipole tracing method in normal subjects]. AB - To determine the normal pattern of the short latency visual evoked potentials (SVEP) in clinical diagnosis, in a previous report, the normal responses were classified into the following three types: uniform type, brainstem dominant type and occipital dominant type, according to the strength of the potentials. In the present report the latencies of N40 and P50, which constitute the SVEP, were investigated. In addition, the burst origin of these potentials was investigated using the dipole tracing method for P50 obtained through dynamic topography. Optic nerve potentials of N40 appeared first in the anterior region (from 37.1msec to 40.4msec following the stimulus) after the fourth retinal oscillatory potentials and soon extended to the posterior region (after about 2msec). This potential appeared in approximately about 65%, because of the low amplitude. P50 appeared 45.8-53.6msec after the stimulus about 100% and burst 2-4 times in the same place. Using the dipole tracing method, the origin of P50 was estimated to the near the deep center of the brain, probably around the brainstem. The same results were obtained using dynamic topography. PMID- 2603847 TI - [Age changes in pupillary light reflex. A demonstration by means of a pupillometer]. AB - A new binocular infrared video-pupillograph (C-2515, Hamamatsu Photonics) with a solid state vidicon tube was developed. Various pupil parameters were instantaneously analyzed by a built-in computer system. The equipment also enabled storage of the data on diskettes. A light reflex, induced by a photic stimulus with a duration of 250 msec (intensity: 3,000 troland) was studied. Several parameters of the light reflex were analyzed. These were: pupil area, change in the area of light stimulus, rate of constriction, latency time, and dilatation time at 63% of the amplitude. A total of 160 subjects (320 eyes) was studied. The ages ranged from 5 to 84 years, and subjects were placed in appropriate ten-year age groups (e.g., 0-9 years, 10-19, 20-29, 30-39, etc.). Ten males and 10 females were included in each group. The light reflex was studied in both eyes. The pupil area reduced as the age advanced, with negative correlation. The pupil area in females over 50 years showed a steeper reduction in size, possibly due to hormonal influences. The latency time at 20 years old was the shortest. In subjects below 10 and over 60 years, the latency time was significantly prolonged when compared with the other age groups. The ratio of the velocity of constriction against the velocity of dilatation was calculated and a negative correlation was seen. This may indicate that there are sympathetic influences related to aging and pupil dynamics. The results revealed that an examination of the light reflex by this new pupillography expressed the precise influence of aging on the pupil. PMID- 2603848 TI - [Morphological study of innervation of orbicularis oculi in the cat with respect to motoneurons, nerve fibers and muscle fibers]. AB - It has been suggested that the orbicularis oculi muscle functions in different modes of action in the orbital portion and in the palpebral portion. To study the anatomical correlation between the localization of muscular division and the size of motoneurons in facial nucleus, the retrograde tracing method was used. A histochemical study on the type of muscle fibers was also performed. The relationship between the motoneurons, nerve fiber and muscle fiber was discussed in terms of the functional organization of the palpebral or orbital orbicularis oculi. We injected a tracer of 50% horseradish peroxidase (HRP) into the orbital and/or palpebral portion of the orbicularis oculi muscle and HRP-labelled motoneurons at the brainstem were studied. In the facial nucleus, four subnuclei have been described: the ventrolateral, ventromedial, dorsolateral and dorsomedial. HRP-labelled motoneurons which innervated both the orbital and palpebral portions were spindle shaped and were found ipsilaterally in the dorsolateral subnucleus, and were distributed rostrocaudally. The histogram of the average soma diameter traced by the injection in the orbital portion presented two peaks at 30 microns and 40 microns in contrast to one peak of palpebral portion. Secondly, a histochemical study using alkali (pH 10.4) preincubated ATPase and acid (pH4.3) preincubated ATPase and NADH stain was performed. It was found that the muscle fibers of the orbital part were composed predominantly of large and middle diameter group II B, while the palpebral part consisted mainly of small diameter group II A. By diameter analyses of the facial nerve fibers, it was found that the myelinated nerve fibers consisted of 3 peaks in terms of the magnitude of histogram. PMID- 2603849 TI - [Experimental retinal vein obstruction induced by transadventitial administration of thrombin in the rabbit]. AB - Retinal venous obstruction with typical flame-shaped hemorrhage was experimentally produced in the rabbit by transadventitial dropping of thrombin on target vessels by vitreous surgery techniques. The changes were studied ophthalmoscopically, light and electron microscopically. Flame-shaped retinal hemorrhage appeared within 24hr after the maneuver of thrombin dropping, following the initial appearance of small hemorrhage during the first 8 to 12hr of the experiment. Microscopic study revealed the process of subendothelial fibrin-thrombus formation in the target venules. Thrombus formation began 6hr after dropping of thrombin and vascular lumina were markedly narrowed by 24hr. No endothelial defect was found in the target venule between 6 and 12hrs after thrombin dropping, though fibrin-platelet thrombi were often found in the lumina of the venules. In the arteriole, on the other hand, intramural thrombus was seen only in the earlier stage, not later than 6hr after dropping of thrombin, in the area peripheral to the site of dropping. These findings suggested the possibility of transmural effects of thrombin as well as participation of arterioles in thrombogenesis, and supports the usefulness of this experimental model for the study of retinal venous obstruction. PMID- 2603850 TI - [Electron microscopic study of the iris and bulbar conjunctiva of Werner's syndrome]. AB - We observed the iris and the upper limbal conjunctiva from the two cases of Werner's syndrome by transmission electron microscopy. Numerous microfibrils were seen between the iris pigment epithelium and the dilator muscle, and within the stroma of the conjunctiva in both patients' eyes. These similar findings in the irides of both patients suggested the relationship between the microfibrils and Werner's syndrome. Many melanosome complexes were found in iris melanocytes, and the basement membrane of the iris vessels showed marked thickening. These findings seemed to be the changes caused by aging in cases of Werner's syndrome. PMID- 2603851 TI - [Evaluation of color pattern VECP in deutan]. AB - Using an Equi-Energy-Color Pattern Generator, color vision experiments were performed on nine normal subjects, six cases of deuteranomalies, and six cases of deuteranopias with the use of Visually-evoked cortical potentials (VECPs). Checkerboard patterns, consisting of the pairing of any chosen one of three colors with its complementary color in terms of equal energy, were used. The pairing of a neutral color with its complementary color of protan, deutan and tritan were displayed on a color TV monitor. We measured the amplitude and latency of P100 component of VECPs. Cases of deuteranopia showed significantly smaller amplitude and longer latency of P100 component in protan and deutan responses than did normal subjects. Cases of deuteramomaly showed significantly smaller amplitude and longer latency of P100 component in only protan response compared to those of normal subjects. It was possible to objectively detect the deutan in color pattern VECPs. PMID- 2603852 TI - [Quantitative assessment of aqueous flare intensity and cell count in uveitis]. AB - In an attempt to evaluate the validity of the laser flare-cell meter in in iridocyclitis, we conducted a comparative study of slit-lamp examination and flare-cell meter measurements in 251 eyes of uveitis patients. A significant correlation was observed between the two methods both in the measurement of flare intensity (Kendall tau = 0.580, p less than 0.001) and cell count (tau = 0.390, p less than 0.001). However, there were wide variations in grading within groups and large overlaps in scores between groups. These results were thought to be attributable to differences in the two examination methods. Flare-cell meter demonstrated high sensitivity for flare measurements, while there were some cases where low numbers of cells, which could be observed by a slit-lamp, were undetectable by the flare-cell meter. Patients with Behcet's disease were divided into three groups based on the interval from an ocular attack episode. Flare-cell meter examination revealed that flare intensity values remained abnormally high even in patients free from an attack episode for more than six months prior to the examination (p less than 0.001). It was considered that disruption of the blood-aqueous barrier exists permanently in patients with Behcet's disease. PMID- 2603853 TI - [Electro-ophthalmological analysis of Behcet's disease]. AB - Six patients with complete type Behcet's disease were studied electro retinographically and electro-oculographically. The electrical responses tested include the hyperosmolarity response in the EOG, the oscillatory potentials and the rapid off-response in the ERG. The oscillatory potentials diminished in five eyes of four cases. In all except one of these eyes the rapid off-response and the hyperosmolarity response were within normal ranges. The hyperosmolarity response was suppressed in one eye which suffered from severe diffuse uveitis and iridocyclitis accompanied with hypopyon. The a-wave, the b-wave, the oscillatory potentials and the rapid off-response were also abnormal in this eye. The hyperosmolarity response was abnormal in an eye with severe ocular lesions of Behcet's disease, while the oscillatory potentials were frequently abnormal even in the earlier stages of the disease. The hyperosmolarity response originates in the retinal pigment epithelial layer. The oscillatory potentials originate in the inner retinal layer. Our findings are compatible with the hypothesis that the initial retinal lesions take place in the inner retinal layer in Behcet's disease. PMID- 2603854 TI - [Scanning electron microscopy of the rabbit crystalline lens]. AB - To study the relationship between the fiber process and suture line of the rabbit crystalline lens, the whole surface of each layer of the lens was observed by scanning electron microscopy. The interlocking processes are well developed within an area of 20 to 40 microns from the suture line and within an area of 600 microns in an extended direction from the end of the suture line. Lateral large processes are noted within 20-40 microns from the cortical suture and were extensively distributed within 600 microns on extended direction from the end of the anterior suture line. Ball and socket junctions were noted in the cortex, and globular patterns were noted in the fetal nucleus. As a result, the suture line is a center of the anatomic structure supported by the interlocking processes and lateral large processes. PMID- 2603855 TI - [Studies on diameter distribution of axons in the optic pathway in human glaucoma]. AB - The distribution of diameters of axons and somas at the level of the optic nerve, lamina cribrosa and retina were compared between human glaucomatous eye and normal control eyes. At the level of lamina scleralis of the glaucomatous eye, there was a tendency for large nerve fibers to be lost in the arcuate nerve fiber area particularly in the inferior arcuate nerve fiber area, where the corresponding visual field defect was detected. The percentages of large axons and somas in the arcuate nerve fiber area decreased in the glaucomatous eye both at the level of the optic nerve, retina but most of all at the level of lamina cribrosa. These results suggest that the mode of optic nerve damage in early glaucoma is characterized by the selective damage of large nerve fibers, which is most severe at the lamina cribrosa. PMID- 2603856 TI - Fear and boldness. PMID- 2603857 TI - The Webster amicus curiae briefs: perspectives on the abortion controversy and the role of the Supreme Court. Introduction: did the amici effort make a difference? PMID- 2603858 TI - Brief for bioethicists for privacy as amicus curiae supporting appellees. PMID- 2603859 TI - Webster and women's equality. PMID- 2603860 TI - Webster and the fundamental right to make medical decisions. PMID- 2603861 TI - Abortion counseling and the First Amendment: open questions after Webster. PMID- 2603863 TI - The role of stare decisis in the reconsideration of Roe v. Wade. PMID- 2603862 TI - Brief for 885 law professors in support of maintaining adherence to the Roe decision. PMID- 2603864 TI - Judicial standard of review and Webster. PMID- 2603865 TI - Webster, vagueness and the First Amendment. PMID- 2603866 TI - Roe v. Wade is constitutionally unprincipled and logically incoherent: a brief in support of judicial restraint. PMID- 2603867 TI - The Webster amicus curiae briefs: perspectives on the abortion controversy and the role of the Supreme Court. Conclusion: the future of abortion as a "private choice". PMID- 2603868 TI - The incompetent developmentally disabled person's right of self-determination: right-to-die, sterilization and institutionalization. AB - The developmentally disabled, specifically those mentally incompetent from birth, are entitled to a full panoply of constitutional rights and protections. These rights include the right to terminate life-sustaining treatment, the right of procreative integrity and the right not to be involuntarily institutionalized. However, the mentally incompetent developmentally disabled are generally unable to exercise these rights. This Note asserts first that proper procedural safeguards are necessary to guarantee the exercise of these constitutional rights by the incompetent disabled individual. Second, the Note focuses upon how best to preserve the disabled person's autonomy. The Note subsequently rejects the substituted judgment standard as a legal fiction, and endorses the best interest test which necessarily comports with the evidence, and properly accounts for the disabled person's incompetency. PMID- 2603869 TI - The pharmacist as educator in biotechnology. PMID- 2603870 TI - Biotechnology products: new opportunities and responsibilities for the pharmacist. AB - The opportunities and responsibilities of pharmacists with respect to the new biotechnology products are described. Recent advances in the fields of molecular genetics and nucleic acid chemistry have resulted in a proliferation of biotechnology products. Those produced by recombinant DNA techniques offer particular promise for the treatment of a wide variety of medical disorders such as cancer, anemia, neutropenia, diabetes, and myocardial infarction. Since the turn of the century, the pharmacy profession has expanded its role from drug preparation and distribution to modern clinical pharmacy, in which pharmacists act as a source of drug information for physicians, nurses, and patients. In response to the new biotechnology revolution, pharmacists must once again undergo a role expansion, this time actively assuming responsibility for educating themselves about the nature and clinical use of the new biopharmaceuticals. The curriculum of students undergoing training in pharmacy should cover such areas as immunoglobulins, immunomodulators, growth hormones, targeted drug-delivery systems, and advanced diagnostic techniques that use biotechnology products. Continuing-education programs in these areas will update currently practicing pharmacists on the new biotechnology products. Although use of biologic proteins is currently targeted toward hospitalized patients, future advances may allow for dispensing these new drugs through community pharmacies as well. Therefore, change will be necessary at all levels of the pharmacy profession. As pharmacists accept the responsibility of dispensing, monitoring, and providing information about the new biotechnologic agents, they will enhance the rational use of these compounds. PMID- 2603872 TI - Pharmacists as principal investigators in clinical drug research. PMID- 2603871 TI - Handling ganciclovir as a cytotoxic agent. PMID- 2603873 TI - Descriptive labeling may reduce prescription errors. PMID- 2603874 TI - Open letter to organizations funding pharmacy research. PMID- 2603875 TI - Evaluating the real costs of drug therapy. PMID- 2603876 TI - Visual compatibility of amphotericin B and flush solutions. PMID- 2603877 TI - The case for fax machines. PMID- 2603878 TI - Feldene capsules are prescription-only worldwide. PMID- 2603879 TI - Monitoring physician drug prescribing. PMID- 2603880 TI - The 1980s in review. PMID- 2603881 TI - Educational differentiation of the pharmacy work force. AB - A model of the pharmacy work force in which pharmacists are differentiated and quantified on the basis of their professional education is described, and the model is used to analyze work force data for 1978 and 1987. The educational differentiation of the pharmacy work force was represented by a three-tiered pyramid in which the base, second, and third levels comprised pharmacists with a B.S. degree, a Pharm.D. degree, and residency or fellowship training, respectively. The number of pharmacists at each level was tabulated for 1978 and 1987 by using data from the National Center for Health Statistics, the American Association of Colleges of Pharmacy, ASHP, and other sources. In 1987, as in 1978, more than 90% of pharmacists had no formal training beyond the B.S. degree. However, the proportion of pharmacists with Pharm.D. degrees did increase from 1 in 30 to 1 in 16, and proportionately more pharmacists were receiving post Pharm.D. training. Large state and regional differences were seen in the number and educational level of pharmacists. Differentiation in the physician and nursing work forces was examined; the physician work force was highly specialized, but nurses showed a more balanced differentiation. An increase in the demand for postgraduate training of pharmacists was projected. The educational differentiation model shows that the pharmacy work force is highly undifferentiated and that education at the Pharm.D. level should be emphasized. Such emphasis will increase the demand for residency and fellowship programs and improve the image of pharmacy as a profession. PMID- 2603882 TI - Pharmaceutical continuing-education program based on a core curriculum. AB - The use of a core curriculum concept in the establishment of a comprehensive continuing-education program is described. A departmental staff development committee was selected to develop a core curriculum of topics for professional continuing education. Six core curriculum areas of interest and importance were identified: cardiology; infectious disease; total parenteral nutrition, acid-base balance, and fluid and electrolytes; pharmacy management; critical-care medicine; and pharmacokinetics. Coordinators were selected from the staff to identify topics and speakers in each core curriculum area. The drug information center was assigned responsibility for logistical aspects of the program such as scheduling, evaluations, objectives, information support, and providing continuing-education credit. A survey of staff perceptions revealed a very positive view of the program. The staff rated the program highly as meeting their needs for continuing education credit, as an employee benefit, and in covering topics related to their practice. The core curriculum concept has been shown to be a successful and effective approach to the establishment of a comprehensive continuing-education program. PMID- 2603883 TI - Pharmacists' evaluations of the nonprescription availability of metaproterenol, cimetidine, ibuprofen, and nystatin. AB - The relative importance of six switch evaluation criteria in pharmacists' evaluations of the appropriateness of switching four drugs from prescription to nonprescription status was assessed. A questionnaire was constructed for three potential switch candidates (metaproterenol, cimetidine, and nystatin) and one already switched drug (ibuprofen 200 mg). Pharmacists were asked to judge (1) the overall appropriateness of switching these four drugs and (2) the appropriateness of switching these drugs based on the FDA switch criteria of safety, effectiveness, and labeling and two other proposed criteria: the need for oral counseling about the product and perceived market need for the product. Additionally, pharmacists were asked to rate whether they believed the study drugs would be profitable to their pharmacies if the drugs were switched to nonprescription status. A total of 1161 pharmacists were reached by the mailings, of whom 417 (34.8%) responded. Only ibuprofen 200 mg received a positive overall switch approval rating from the pharmacists; cimetidine received the lowest rating. The six evaluation criteria were tested for significant association with pharmacists' overall judgment of the appropriateness of switching each drug. The three most influential criteria were safety, labeling, and market need for the product, respectively. Profitability to the pharmacy was not significantly associated with pharmacists' overall judgment of switch appropriateness. Regression analysis identified safety, labeling, and market need as important in the evaluation of all four drugs, and pharmacists' evaluation of the relative importance of these criteria was a predictor of their overall judgment of the appropriateness of a switch. Consumer safety, not personal economic interests, most influenced pharmacists' judgment of the appropriateness of a switch from prescription to nonprescription status for four drugs. PMID- 2603884 TI - Effect of interventions on prescribing of antimicrobials for prophylaxis in obstetric and gynecologic surgery. AB - The effect of interventions on the conformity of physicians with guidelines for the appropriate use of antimicrobial prophylaxis in obstetric and gynecologic surgery is reported. Guidelines on the appropriate use of antimicrobial prophylaxis in common obstetric and gynecologic surgical procedures were developed in late 1986 by the antibiotic subcommittee at a 1100-bed tertiary-care teaching facility. The guidelines were not adopted immediately by the department of obstetrics and gynecology (OB-GYN). An audit of the medical records of women who had received antimicrobial therapy for abdominal and vaginal hysterectomies and emergency cesarean sections during January through March 1987 showed that cefoxitin was used in 68% of the cases instead of the less expensive and equally efficacious cefazolin as recommended in the guidelines. The projected annual cost of this nonconformity was $26,500. After the subcommittee informed the physicians about the guidelines and the audit results, the OB-GYN department adopted the guidelines. A second audit performed one year later showed that cefazolin was used in the recommended manner in 93% of cases; projected annual cost savings were $25,000. Both audits showed that prophylactic treatment was inappropriately prolonged in 6% of cases. Substantial cost savings were realized by minimizing inappropriate antimicrobial drug use through efforts to promote rational and cost effective therapy. PMID- 2603885 TI - System for verifying use of controlled substances in anesthesia. PMID- 2603886 TI - Use of an aminoglycoside-monitoring form to improve communication among nurses, phlebotomists, and pharmacists. PMID- 2603887 TI - Aerosol inhaler technique in children with asthma. PMID- 2603888 TI - Formulary management of biotechnological drugs. PMID- 2603890 TI - Ofloxacin. PMID- 2603889 TI - Mechanisms and how to treat heart failure. PMID- 2603891 TI - Ofloxacin: a pharmacodynamic advance in quinolone antimicrobial therapy. Proceedings of a symposium. November 18 to 19, 1988, Phoenix, Arizona. PMID- 2603892 TI - Pharmacokinetics of ofloxacin. An overview. AB - Ofloxacin pharmacokinetics after oral and parenteral doses were investigated in healthy young and geriatric volunteers and renally impaired patients. After oral administration of single 100- to 600-mg doses to healthy younger volunteers, renal recovery indicates that the amount absorbed increases linearly from 100 to 600 mg. More than 70 percent of an oral dose is recovered in the urine as unchanged ofloxacin, and only minimal amounts, less than 5 percent of the dose, are recovered as the metabolites, desmethyl ofloxacin and ofloxacin N-oxide. After multiple (twice daily) oral administration of 400-mg doses to younger and older (65 to 81 years) healthy volunteers, a modest accumulation (i.e., maximal concentration increased about 50 percent), as predicted by single-dose data, is observed, and steady-state is achieved within 48 hours of the initiation of twice daily dosing. In the young and elderly, ofloxacin is eliminated with a half-life of five to seven hours, independent of dose. In the renally impaired, however, there is a linear correlation between the half-life of ofloxacin and creatinine clearance, and this requires dose adjustment when the creatinine clearance rate is less than 50 ml/minute. The pharmacokinetics of ofloxacin also were investigated after intravenous administration of single 200- and 400-mg doses and multiple twice-daily 400-mg doses. After intravenous dosing, ofloxacin exhibits a pharmacokinetic profile similar to that seen after oral dosing, which supports the almost total oral absorption and the interchangeability of both forms of therapy. The pharmacokinetics of the compound indicate that, except for cases of renal impairment, little or no dosage adjustment is necessary. PMID- 2603893 TI - Drug-drug interactions affecting fluoroquinolones. AB - In a three-week study, the metabolism of the bronchodilator theophylline and its major metabolites formed by C-8 oxidation (1,3-dimethyluric acid) and N demethylation (3-methylxanthine and 1-methyluric acid) was investigated in two healthy volunteers. Metabolic studies were performed following intravenous infusion of a single 6 mg/kg dose of aminophylline. During Week 1, theophylline was given alone (blank period), and during Weeks 2 and 3 it was given during oral coadministration of ofloxacin and enoxacin, respectively. Dosage of each quinolone was 200 mg twice daily for four days, starting three days prior to the theophylline infusion. During enoxacin coadministration, elimination half-lives of theophylline increased from 8.7 to 17.4 hours and from 6.1 to 12.3 hours, respectively. Total body clearance of theophylline decreased in both volunteers, whereas renal clearance did not alter. From this it was concluded that the decreased elimination results from a reduced metabolic clearance. During enoxacin coadministration, the formation of the metabolites 1-methyluric acid and 3 methylxanthine clearly was decreased, whereas the formation of 1,3-dimethyluric acid was less affected compared with the blank period. Interference with theophylline disposition by enoxacin is based predominantly on inhibition of microsomal N-demethylation. Ofloxacin comedication did not cause a change in the plasma parameters or renal excretion of theophylline and its metabolites compared with the blank period. PMID- 2603894 TI - Efficacy and safety of ofloxacin in the treatment of nongonococcal sexually transmitted disease. AB - This study compared doxycycline with ofloxacin in the treatment of nongonococcal urethritis in men and mucopurulent cervicitis in women and compared both drugs in the treatment of infections due to Chlamydia trachomatis in both men and women. Informed consent was obtained from all subjects. Eighteen men with nongonococcal urethritis and 12 with previously positive chlamydial cultures were randomly treated with doxycycline or ofloxacin. Eleven women with mucopurulent cervicitis, 14 with a previous positive untreated chlamydial culture, and nine having sexual contacts with men known to have chlamydial urethritis also were randomly treated. Culture specimens for chlamydia were obtained before treatment, five to nine days after therapy (return visit 1), and 21 to 28 days after therapy (return visit 2). Cultures for Ureaplasma urealyticum were obtained only in men. There were no significant differences in results in patients treated with doxycycline or ofloxacin. All but three of 20 men with symptoms were symptom-free on return visit 1 and all were symptom-free on return visit 2. Thirteen women with mucopurulent cervicitis had all resolved at visit 1, although signs of cervicitis reappeared at the second visit in two patients treated with doxycycline and one treated with ofloxacin. All patients with positive chlamydial cultures had negative cultures at the first return visit. One patient treated with doxycycline was positive at the second return visit. Laboratory and clinical abnormalities were mild and did not prevent completion of therapy. These data, together with previous published and unpublished data, indicate that ofloxacin is as effective as doxycycline in the treatment of chlamydial infections. The study also demonstrated that ofloxacin and doxycycline were equally effective in the treatment of nongonococcal urethritis in men and mucopurulent cervicitis in women. PMID- 2603895 TI - Central hemodynamic assessment of normal term pregnancy. AB - Ten carefully screened primiparous patients between 36 and 38 weeks' gestation underwent pulmonary artery catheterization, arterial line placement, and central hemodynamic assessment in the left lateral recumbent position. Studies were repeated in the same patients between 11 and 13 weeks post partum. Compared with the nonpregnant state, there was a significant fall in systemic vascular resistance, pulmonary vascular resistance, colloid oncotic pressure, and colloid oncotic pressure-pulmonary capillary wedge pressure gradient by the late phase of the third trimester (p less than 0.05). Pregnancy was associated with a significant rise in cardiac output and pulse in all patients (p less than 0.05). There was no significant change in pulmonary capillary wedge pressure, central venous pressure, left ventricular stroke work index, or mean arterial pressure. Normally the late phase of the third trimester is not associated with hyperdynamic left ventricular function as assessed by the left ventricular stroke work index/pulmonary capillary wedge pressure ratio. PMID- 2603896 TI - The central hemodynamics of severe preeclampsia. AB - Swan-Ganz hemodynamic monitoring in 49 antepartum patients with severe preeclampsia revealed a variable hemodynamic profile. The majority of patients had normal left ventricular filling pressure (8.4 +/- 0.2 mm Hg), normal to high cardiac index (4.4 +/- 0.1 L.min-1.m2), and upper normal to moderately elevated systemic vascular resistance (1226 +/- 37 dynes.sec.cm-5). Eight patients had pulmonary edema and their findings included high wedge pressure (18 +/- 1 mm Hg), upper normal to high cardiac index (4.9 +/- 0.5 L.min-1.m2), and normal systemic vascular resistance (964 +/- 50 dynes.sec.cm-5). Left ventricular function was hyperdynamic in 73% of the 49 patients. Patients with chronic hypertension and superimposed preeclampsia were hemodynamically indistinguishable from patients with preeclampsia alone. We conclude that, in general, preeclampsia is a high cardiac output state associated with an inappropriately high peripheral resistance. The normal wedge and central venous pressures suggest central redistribution of intravascular volume if the generally accepted reports of decreased plasma volume in preeclampsia are correct. PMID- 2603897 TI - Cardiovascular changes in early phase of pregnancy. AB - To assess the magnitude and timing of cardiovascular changes in pregnancy, eight subjects were serially studied before conception and at 8, 16, and 24 weeks' gestation. With the use of M-mode echocardiography, cardiac output, ejection fraction, stroke volume, and end-diastolic volume were calculated from left ventricular dimensions with subjects in the left lateral position. Systemic vascular resistance was calculated with the use of cardiac output and simultaneously obtained measurements of arterial pressure. Cardiac output increased 1 L/min at 8 weeks' gestation, which represented greater than 50% of the total change seen. Cardiac output increased primarily because of stroke volume rather than heart rate. By 8 weeks' gestation, systemic vascular resistance had fallen to 70% of its preconceptional value. Thus when subjects are studied before conception and during the early phase of pregnancy, the majority of the pregnancy-induced changes in these parameters occur during the embryonic period. PMID- 2603898 TI - The effects of maternal exercise on early pregnancy outcome. AB - This study was designed to test the hypothesis that vigorous aerobic exercise during both the periconceptional period and early pregnancy increases the incidence of abnormal early pregnancy outcome. Exercise performance was prospectively monitored before and during pregnancy in 47 recreational runners, 40 aerobic dancers, and 28 physically active, fit controls. Pregnancy was diagnosed by an early test for beta-subunit human chorionic gonadotropin and viability was confirmed by ultrasonography at 40 days' conceptional age. Spontaneous abortion occurred in 19% of the pregnancies. The incidence was 17% in the runners, 18% in the aerobic dancers, and 25% in the controls. At term, one congenital abnormality was detected in each of the three groups. Late pregnancy events, potentially related to abnormalities of placentation, were limited to two cases of mild pregnancy-induced hypertension. We conclude that, in physically fit women, continuation of these types of aerobic activity at intensities between 50% and 85% of maximum during the periconceptional period and early pregnancy does not appreciably alter early pregnancy outcome. PMID- 2603899 TI - Oxygen consumption during treadmill exercise before, during, and after pregnancy. AB - This study was designed to test the hypothesis that the amount of oxygen required to complete a specific treadmill exercise protocol changes during pregnancy as a function of gestational age, weight gain, and an individual's exercise regimen. The amount of oxygen required to complete a three-step, graded workload treadmill protocol was monitored before, every 6 to 8 weeks during, and after a clinically normal, accurately dated, singleton pregnancy in 18 fit, recreational athletes. Nine subjects continued a moderate- to high-intensity exercise regimen and nine did not. The amount of oxygen required to complete each stage of the protocol decreased significantly (6% to 15%) in both groups in early pregnancy. In the women who continued exercise, the amount of oxygen required remained at or significantly below that required before conception for the remainder of the pregnancy and the initial postpartum period. Conversely, in the women who discontinued regular exercise, the amount of oxygen required for each stage rose progressively throughout the remainder of pregnancy at an average rate of 2% per lunar month. It peaked in the thirty-seventh week and remained significantly elevated 7 weeks post partum. However, when the data were corrected for the additional requirement imposed by pregnancy weight gain, net efficiency was increased in both groups throughout pregnancy. These data support three conclusions. First, the efficacy of low- to moderate-intensity treadmill exercise in physically active women is improved in early pregnancy. Second, this increased efficiency is masked later in pregnancy by the effects of weight gain. Third, the degree of efficiency is enhanced throughout pregnancy in women who continue a regular exercise regimen at or above a basic conditioning level. PMID- 2603900 TI - Exercise prescription in pregnancy: weight-bearing versus non-weight-bearing exercise. AB - Bicycle ergometry (non-weight-bearing exercise) and treadmill (weight-bearing exercise) were compared to assess physiologic responses to similar work loads. A total of 22 subjects at 29.3 +/- 1.6 (+/- SEM) weeks' gestation who performed non weight-bearing exercise were compared with 15 similarly fit subjects at 26.1 +/- 2.3 weeks' gestation who performed weight-bearing exercise at three submaximal levels. Measurements by indirect calorimetry indicate preferential carbohydrate use during non-weight-bearing exercise at submaximal levels. PMID- 2603901 TI - Human fetal behavioral states after vibratory stimulation. AB - A total of 14 healthy pregnant women between 37 and 41 weeks' gestational age were studied to determine the effects of a 5-second external vibratory stimulus (100 Hz, square wave) on human fetal behavioral states. Fetal behavioral state observations were made with simultaneous recordings of fetal heart rate, gross fetal body movements, and fetal eye movement between 8:30 AM and 4:00 PM. During the first episode of behavioral state 1F (quiet sleep state) greater than or equal to 10 minutes duration on two consecutive half days, the vibratory stimulus was placed on the surface of the maternal abdomen over the fetal head. Each fetus received one 5-second vibratory stimulus during either the first or second half day of observation. The time at which the instrument was applied but no vibratory stimulus was administered was considered as the control period. All women were then observed for 2 hours after the control period and after stimulation. A transition period from a quiet sleep state to a stable active sleep state (state 2F, rapid eye movement sleep) averaged less than or equal to 3 minutes after stimulation, as compared with 23 minutes after the control period. These changes in fetal behavioral states persisted for 20 minutes after vibratory stimulation. There also was an immediate and sustained increase in long-term fetal heart rate variability, the number of fetal heart rate accelerations and gross fetal body movement during the first 20 minutes after stimulus, without changes in basal fetal heart rate. We hypothesize that changes in fetal behavior seen after application of low frequency vibratory stimulus are more physiologic than the profound changes in fetal heart rate and gross fetal body movement previously described after vibratory acoustic stimulation with an electronic artificial larynx. PMID- 2603902 TI - The effect of vibroacoustic stimulation on the nonstress test at gestational ages of thirty-two weeks or less. AB - The effect of vibroacoustic stimulation on the nonstress test at gestational ages of less than or equal to 32 weeks was studied in 15 patients who underwent a total of 316 nonstress tests starting at 20 to 25 weeks' gestation. There were 168 nonreactive nonstress tests that were followed by 3 seconds of vibroacoustic stimulation. The incidence of reactive nonstress tests after vibroacoustic stimulation was significantly increased after 26 weeks' gestation. This may have clinical applicability and may be related to functional maturation of the fetal auditory system. PMID- 2603903 TI - Effects of low-frequency vibration on human term fetuses. AB - Thirteen healthy pregnant women between 37 and 41 weeks' gestational age were studied to examine effects of a 5-second external vibratory stimulus (100 Hz, square wave) on fetal heart rate, fetal breathing, and gross fetal body movement patterns. All fetuses were stimulated during an episode of low fetal heart rate variability (mean minute range less than or equal to 32 milliseconds for greater than or equal to 5 minutes) lasting at least 5 minutes. There was an immediate and sustained increase in long-term FHR variability, number of FHR accelerations, and gross fetal body movements after stimulation. Fetuses made breathing movements more irregularly after vibratory stimulus. We hypothesize that external low-frequency vibratory stimulus, applied during episodes of low fetal heart rate variability, causes a change from a state of quiet sleep to a state of rapid-eye movement sleep in healthy term fetuses. PMID- 2603904 TI - Nifedipine pharmacokinetics during preterm labor tocolysis. AB - Nifedipine, a calcium entry blocker, has known relaxing effects on the myometrium. Thirteen women in preterm labor received nifedipine for tocolysis. Blood samples obtained serially during treatment and at the time of delivery were assayed for maternal and neonatal nifedipine concentrations. The peak concentration of nifedipine during sublingual therapy ranged from 23.4 to 197.9 ng/ml and reflected substantial interpatient variability. The mean (+/- SD) measurable trough value in patients who received 20 mg of nifedipine orally every 6 hours was 7.2 +/- 5.5 ng/ml. The maternal mean half-life of nifedipine was 81 minutes (range 49 to 137 minutes). At delivery, neonatal nifedipine levels were nondetectable in 6 of the 11 neonates available for study; in 5, values ranged from 29.5 to 1.8 ng/ml. From these results we conclude that both sublingual and oral nifedipine treatment results in variable but usually measurable maternal plasma concentrations and that placental transfer of nifedipine occurs. PMID- 2603905 TI - The effect of intravascular transfusion on umbilical venous pressure in anemic fetuses with and without hydrops. AB - Human fetal umbilical venous pressure was measured during 20 intravascular transfusions performed for treatment of hemolytic anemia. The mean (+/- 1 SEM) gestational age at the time of transfusion was 29.3 +/- 1 weeks and the mean beginning hematocrit was 27% +/- 2%. The mean volume of infused packed red blood cells (70% hematocrit) was 90.3 +/- 7 ml. The mean hematocrit at completion of the procedure was 48% +/- 1%. In nonhydropic fetuses umbilical venous pressure rose progressively from 6.7 +/- 1 mm Hg at the start of transfusion to 10.9 +/- 1 mm Hg at the completion of transfusion (p less than 0.002). However, most fetuses who began the infusion with a normal umbilical venous pressure ended the transfusion with a normal umbilical venous pressure (less than 10 mm Hg). Fetuses with immune hydrops (n = 2) had elevated umbilical venous pressure values before the initiation of transfusion therapy when compared with the first transfusion of nonhydropic fetuses (12.5 +/- 0.5 vs. 5.7 +/- 1 mm Hg, p = 0.01). However, the umbilical venous pressure measurements declined into the normal range within 24 hours of the first transfusion; this normalization was too rapid to be explained by the reversal of liver hypertrophy or portal hypertension. There was no demonstrable relationship between the rise in umbilical venous pressure and either the gestational age, the volume transfused, or the rise in hematocrit. This study demonstrated: (1) In terms of the umbilical venous pressure, direct intravenous infusion of the human anemic fetus is well tolerated; (2) the elevated umbilical venous pressure associated with immune hydrops can correct rapidly with red blood cell replacement. PMID- 2603906 TI - Human fetal tricuspid and mitral deceleration time: changes with normal pregnancy and intrauterine growth retardation. AB - Studies in instrumented adults have shown an association between Doppler echocardiography-derived atrioventricular valve deceleration times and ventricular function. To determine how gestational age affects deceleration time in the tricuspid and mitral valve, pulsed Doppler ultrasonographic examinations were performed in 54 normal human fetuses. In addition, 26 fetuses with growth retardation and the absence of end-diastolic Doppler velocities in the umbilical artery were examined. Measurements were obtained from strip chart recordings; between three and five beats were used to obtain an average heart rate, ratio of peak velocity at atrial contraction to peak velocity in early diastole, and deceleration time in early diastole. Deceleration times increased during gestation from 86 +/- 27 to 116 +/- 18 msec in the tricuspid valve and from 98 +/ 25 to 132 +/- 21 msec in the mitral valve. Fetuses with growth retardation and the absence of end-diastolic Doppler velocities in the umbilical artery had longer deceleration times than those of normal fetuses (p less than 0.01). The increase in deceleration time across both atrioventricular valves in normal fetuses may be related to heart rate, an increased rate of ventricular relaxation, or an increase in ventricular compliance. The fetuses with intrauterine growth retardation and the absence of end-diastolic velocities in the umbilical artery have abnormally increased deceleration times; in the abnormal fetus this may be a result of impaired ventricular relaxation or decreased ventricular compliance. PMID- 2603907 TI - Effect of placental laterality on uterine artery resistance and development of preeclampsia and intrauterine growth retardation. AB - We studied 153 pregnant women with normal pregnancies and 147 women with complicated pregnancies (diabetes, hypertensive disorders, and intrauterine growth retardation) to evaluate the association of placental location and the development of preeclampsia, intrauterine growth retardation, and uterine artery resistance. The placental location was determined by real-time ultrasonography, and the uterine artery resistance was determined by continuous-wave Doppler flow velocity waveform analysis. In the presence of preeclampsia or intrauterine growth retardation, up to 75% of the patients had unilaterally located placentas and 25% central placentas, whereas in the absence of these two conditions only 51% of the patients had unilateral and 49% central placentas (p less than 0.02). In patients with unilateral placentas, the incidence of preeclampsia and intrauterine growth retardation was 2.8-fold and 2.7-fold greater than in patients with central placentas (p less than 0.03 and p less than 0.01). Among all patients unilateral placental location was more likely to be associated with abnormal artery flow velocity waveforms than central placental location (p less than 0.001). We conclude that unilateral placental location may predispose to the development of preeclampsia and intrauterine growth retardation by its effect on uterine artery resistance. PMID- 2603908 TI - Esterase activity in second- and third-trimester amniotic fluid: an indicator of chorioamnionitis. AB - Accurate and rapid diagnosis of chorioamnionitis poses a major diagnostic dilemma. We previously reported that leukocyte esterase activity in amniotic fluid, as measured by dipstick assay, could be used as an aid in the diagnosis of chorioamnionitis. This study examines the effectiveness of an in vitro spectrophotometric assay of esterase activity in amniotic fluid. We define baseline levels of esterase activity in uninfected amniotic fluid and demonstrate a quantitative increase when infection is present. Fifty-seven amniotic fluid samples obtained at second- and third-trimester amniocenteses were divided into three parts, one for culture and two for a comparison of esterase activities by the dipstick and spectrophotometric methods. In this study, the spectrophotometric assay, because of its higher specificity and sensitivity in the determination of elevated esterase activity, was shown to be more reliable for predicting chorioamnionitis than either the dipstick or culture method. PMID- 2603909 TI - Rapid chromosome analysis with the use of spontaneously dividing cells derived from umbilical cord blood (fetal and neonatal). AB - An accurate and reproducible method to obtain high-quality metaphases within 24 hours has been developed. Preparations can be derived from cord blood samples obtained either at delivery or by percutaneous umbilical blood sampling. Mitogens are not required. Rapid cytogenetic analysis can facilitate management of pregnancies characterized by malformations or intrauterine growth retardation. PMID- 2603910 TI - High glucose levels decrease proliferation of cultured human fetal cells from placenta. AB - We used the placenta as a source of undifferentiated cells to study the effect high glucose levels can have on human fetal cell proliferation in vitro. Cells were subcultured in a modified minimum essential medium with 10% fetal bovine serum containing either 5.5 mmol/L (100 mg/dl) D-glucose (control), 11 mmol/L (200 mg/dl) D-glucose, or 22 mmol/L (400 mg/dl) D-glucose. Cells grown in mannitol-containing media were used as controls for osmolality. After 3 and 7 days' growth in different media, the labeling index was determined by autoradiographic analysis, and cell numbers were determined with a Coulter counter. The labeling indices for cells grown 3 days in 11 or 22 mmol/L D-glucose were 89% (p less than 0.002) and 84% (p less than 0.001), respectively, of control cells grown in 5.5 mmol/L D-glucose. After 7 days' growth, the labeling indices of cells grown in 11 or 22 mmol/L D-glucose were 84% (p less than 0.002) and 70% (p less than 0.001), respectively, of cells grown in 5.5 mmol/L D-glucose media. There was a significant decrease in the number of cells present at both 3 and 7 days in cultures grown in 22 mmol/L D-glucose compared with control. We conclude that a few day's exposure to high glucose levels can have an effect on proliferation of human placental cells in vitro. We suggest that a glucose effect on proliferation of other cells derived from the products of conception might be one mechanism contributing to abnormal development in some pregnancies of diabetic women. PMID- 2603911 TI - Stimuli for fetal swallowing: systemic factors. AB - Although the fetal gastrointestinal tract is believed to be a major site of amniotic fluid absorption, there is little information with regard to the acute regulation of fetal swallowing. A model for the study of ovine fetal swallowing was developed to incorporate electromyograms, an esophageal flow probe, and a computer data acquisition and analysis program. The fetal swallowing responses to two primary thirst stimuli, plasma hyperosmolality and angiotensin II, were studied. On alternate days, chronically prepared fetal lambs (131 +/- 2 days) received an intravenous infusion of angiotensin II (100 ng/kg per minute) or bolus injections (3 ml) of 0.15 and 3.97 mol/L saline solution. In response to the angiotensin II infusion, fetal systolic (49.3 to 64.7 mm Hg; p less than 0.05) and diastolic (31.1 to 40.5 mm Hg; p less than 0.05) blood pressures significantly increased. However, fetal swallowing did not change from basal rates of 0.85 swallows per minute and a net esophageal flow of 0.98 ml/min. In response to the injection of 3.97 mol/L saline solution, fetal plasma osmolality increased (292 to 306 mOsm; p less than 0.05) and subsequently decreased to 300 mOsm at 15 minutes after the injection. Within 1 minute after injection of the hypertonic saline solution, fetal swallowing activity (6.0 swallows per minute; p less than 0.05) and net esophageal flow (2.4 ml/min; p less than 0.05) significantly increased. Swallowing returned to basal values within 5 minutes after the injection. The data indicate that ovine fetal responses to osmolar thirst challenges are intact at 130 days' gestation. Fetal swallowing and thus amniotic fluid volume may be affected by fetal responses to in utero stimuli. PMID- 2603912 TI - Effect of whole-body pH changes on thoracic duct lymph flow in anesthetized sheep. AB - Physiologic alterations of pH in vitro produce alterations of the oncotic pressure of both plasma and interstitial proteins, the effect being more marked in the latter. Therefore we postulated that by changing an animal's pH we could produce alterations in fluid distribution and affect the whole-body lymph flow rate. To test this hypothesis, we infused seven acutely nephrectomized anesthetized sheep with 2% body weight/volume isosmotic lactated Ringer's solution and bicarbonate (200 mEq) after a 30-minute control period. The fluid was infused over a 10-minute period with 20-minute recovery intervals. To another group of seven ewes, we infused the same volume of lactated Ringer's solution and hydrochloric acid (40 mEq). Throughout the experiment, we continuously measured arterial and venous pressures and lymph flow rate. Every 10 minutes we obtained samples for arterial pH, for hematocrit, and for plasma and lymph protein and osmolality. The infusion of bicarbonate was associated with a comparatively lower peak lymph flow rate (383% over baseline compared with 757% for acid infusion). Also the lymph flow rate after acid infusion started to increase approximately 5 minutes after the beginning of the infusion, as compared with approximately 10 minutes after the base infusion. Acid infusion did not increase arterial pressure, in contrast to the other infusions. The changes in pH obtained with the infusions were insignificant for the Ringer's infusion, +0.17 for the base, and 0.16 for the acid. The plasma/lymph protein concentration ratios at the end of the infusion were no different for acid or base: 112.4% +/- 4.4% and 101.9% +/- 5% (difference from control, mean +/- SEM) respectively (p greater than 0.1). In conclusion, minimal alterations of pH produced alterations in the cardiovascular and lymph flow rate responses to fluid challenge in anesthetized animals. PMID- 2603913 TI - Does furosemide alter the hemodynamic response to rapid intravascular transfusion of the anemic fetal lamb? AB - The purpose of this study was to define the hemodynamic response to rapid intravascular transfusion of the anemic fetal lamb and to determine whether furosemide alters that response. Sixteen experiments were performed in nine chronically instrumented gravid ewes between 0.8 and 0.9 of timed gestation. On day 1 of each experiment, each fetus was subjected to hemorrhage (40 ml/kg of estimated fetal weight) over 1 hour. On day 2, plasma was withdrawn from the stored fetal blood until the hematocrit was approximately 70%, and the packed red blood cells were returned to the fetus intravenously over 10 minutes. Each fetus received either furosemide (2 mg/kg) or control saline solution intravenously at time zero and again at 5 minutes. The order of experiments was randomly determined for each animal. Hemorrhage resulted in a similar decrease in fetal hematocrit in the two groups. The mean +/- SEM fetal hematocrit before hemorrhage was 38 +/- 3% in the furosemide group (n = 8) and 36 +/- 2% in the control group (n = 8). On day 2, the mean +/- SEM fetal hematocrit before transfusion was 28 +/ 2% in the furosemide group and 25 +/- 1% in the control group. There was no significant difference between groups in the fetal hemodynamic response to transfusion. At the end of the transfusion, the fetal central venous pressure had increased from 4.9 +/- 0.5 to 6.2 +/- 0.5 mm Hg in the furosemide group (p = 0.01) and from 3.9 +/- 0.2 to 5.8 +/- 0.3 mm Hg in the control group (p = 0.0001). Fetal mean arterial pressure increased from 42 +/- 1 to 50 +/- 1 mm Hg in the furosemide group (p = 0.0001) and from 40 +/- 1 to 46 +/- 1 mm Hg in the control group (p = 0.0007). Fetal heart rate decreased from 187 +/- 2 to 169 +/- 5 beats/min in the furosemide group (p = 0.004) and from 188 +/- 4 to 170 +/- 5 beats/min in the control group (p = 0.0008). Transfusion did not significantly change fetal pH in either group. At 120 minutes, the fetal PO2 had increased from 17 +/- 1 to 19 +/- 1 mm Hg in the furosemide group (p = 0.03) and from 19 +/- 1 to 21 +/- 2 mm Hg in the control group (p = 0.05). We conclude that rapid transfusion of the anemic fetal lamb resulted in modest increases in fetal central venous pressure and mean arterial pressure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2603914 TI - Intrauterine growth retardation and the circulatory responses to acute hypoxemia in fetal sheep. AB - Intrauterine growth retardation has been produced experimentally by umbilical placental embolization for 9 days (early intrauterine growth retardation) in pregnant sheep. Fetuses with early intrauterine growth retardation had a 20% decrease in mean body weight and 33% decrease in placental blood flow. However, the regional blood flow distribution was not significantly different at rest between the embolized and normally grown fetuses despite the 39% decrease in fetal arterial oxygen content. The purpose of this study was to determine the circulatory responses to acute hypoxemic stress in the early development of intrauterine growth retardation. We found that the regional blood flow distribution was not significantly different during imposed acute hypoxemia between the seven fetuses with early intrauterine growth retardation and seven nonembolized normally grown fetuses. We conclude that growth-retarded fetuses are able to meet basal metabolic oxygen requirements and to respond normally to imposed acute hypoxemia until the placental circulatory reserve capacity is depleted. PMID- 2603915 TI - Prostaglandin E2 metabolism in the human fetal membranes. AB - Prostaglandins play a pivotal role in the initiation and maintenance of labor, but the sources that contribute to the production of primary prostaglandins (prostaglandin E2 and prostaglandin F2 alpha) remain controversial. In decidua, prostaglandin F2 alpha may be formed de novo or from prostaglandin E2 through 9 ketoreductase activity, although it has been suggested that metabolism to 13,14 dihydro-15-ketoprostaglandin E2 through 15-hydroxyprostaglandin dehydrogenase is dominant. To examine this possibility, and to determine changes with labor, we examined interconversions of prostaglandin E2 to prostaglandin F2 alpha, 13,14 dihydro-15-ketoprostaglandin E2 and 13,14-dihydro-15-ketoprostaglandin F2 alpha by dispersed cells of decidua, chorion, and amnion obtained from patients at term elective cesarean section or after spontaneous labor. Incubations were performed with increasing concentrations (1 to 100 ng/ml) of prostaglandin E2 for 2 and 4 hours, and products were measured by radioimmunoassay. The 13,14-dihydro-15 ketoprostaglandin E2 was measured as 11-deoxy-13,14-dihydro-15-keto-11 beta, 16 psi-cycloprostaglandin E2. Basal output of prostaglandin E2 increased between cesarean section and spontaneous labor from 190.6 +/- 109 pg/10(5) cells (+/- SE) to 605.2 +/- 346.8 in amnion, nondetectable to 24.5 +/- 11.2 in chorion, and 18 +/- 16 to 69 +/- 25.8 in decidua. For both cesarean section and spontaneous labor patients there was very little conversion of prostaglandin E2 by the amnion, substantial conversion to 13,14-dihydro-15-ketoprostaglandin E2 by the chorion, and some conversion to 13,14-dihydro-15-ketoprostaglandin E2 by the decidua. Percentage conversions did not change with labor. Prostaglandin F2 alpha was formed by all tissues but only in trace amounts. All tissues from one cesarean section patient showed substantial conversion of prostaglandin E2 to prostaglandin F2 alpha, but very little 13,14-dihydro-15-ketoprostaglandin E2 or 13,14-dihydro-15-ketoprostaglandin F2 alpha formation, indicating either a decrease or deficiency in the 15-hydroxyprostaglandin dehydrogenase activity. We conclude that conversion of exogenous prostaglandin E2 to prostaglandin F2 alpha can occur in intrauterine tissues, but this does not normally contribute significantly to the prostaglandin F2 alpha output by the human decidua and fetal membranes. PMID- 2603916 TI - In vitro release of endothelium-derived relaxing factor by acetylcholine is increased during the guinea pig pregnancy. AB - The relaxation of isolated blood vessels by acetylcholine is dependent on the presence of intact endothelium and its release of a smooth muscle relaxing nitroso-like compound. Pregnancy is associated with altered vascular responsiveness to a variety of agents. Because many of these agents stimulate the release of endothelium-derived relaxing factor, we investigated in vitro the effect of pregnancy on acetylcholine-mediated relaxation of guinea pig uterine and carotid artery rings. The presence of intact and functional endothelium was confirmed both by examination under the scanning electron microscope and by vessel relaxation after the addition of acetylcholine. The addition of acetylcholine to the vessel bath produced dose-dependent relaxation of both carotid and uterine artery segments obtained from pregnant and nonpregnant animals after they had been submaximally preconstricted with phenylephrine. There was a significant increase in both response and efficacy to acetylcholine during pregnancy for both uterine and carotid arteries (p less than 0.0001 for each). The concentrations of endothelial cells (cells per square micrometer) were similar in uterine arteries from pregnant and nonpregnant animals. We conclude that the most likely explanation for these findings is a pregnancy-mediated enhancement of endothelium-derived relaxing factor activity. PMID- 2603917 TI - Effect of pregnancy on uterine and carotid artery response to norepinephrine, epinephrine, and phenylephrine in vessels with documented functional endothelium. AB - The effect of pregnancy on arterial sensitivity to vasoconstrictors is controversial. Some of the controversy may reflect methodologic differences. Vessel reactivity in vitro is altered by both the tension placed on the segment and the presence or absence of functional endothelium. We investigated the effect of pregnancy on guinea pig uterine and carotid arteries to norepinephrine, epinephrine, and phenylephrine. Each vessel segment was stretched to the optimal point along its length-tension curve, and functional endothelium was documented by acetylcholine-stimulated relaxation. A significant dose-response relationship was observed in each vessel for each agent (each p less than 0.0001). Pregnancy was demonstrated to be associated with a significant reduction in both uterine artery response and sensitivity to norepinephrine, epinephrine, and phenylephrine. However, there was no consistent pregnancy-associated effect on carotid artery response and sensitivity. PMID- 2603918 TI - Evaluation of pulsed Doppler echocardiography for measurement of aortic blood flow in the fetal lamb. AB - The purpose of this study was to assess the accuracy of a quantitative, range gated, two-dimensional Doppler echocardiography method for measurement of blood flow in the fetal lamb descending aorta. Comparison was made between this method and measurements determined by an electromagnetic flowmeter placed directly on the aorta in the chest of the fetus. Stroke volume was manipulated acutely either by the removal of blood, the addition of fluid by injection, or by pharmacologic means. During each procedure, descending aortic blood flow was estimated by the Doppler ultrasonography method and compared to the flowmeter recording. The size of the lumen of the aorta determined by echocardiography was correlated with direct measurement during surgery and at autopsy. A total of 359 flow measurements were obtained in 15 fetuses. Doppler ultrasonographic flow studies and electromagnetic flowmeter measurements were found to be highly correlated (r = 0.93). The study demonstrates the accuracy and reliability of the two dimensional pulsed Doppler echocardiography method for measurement of blood flow in the descending aorta in the fetal lamb. PMID- 2603919 TI - Lymph flow rate response to angiotensin II is decreased in pregnant sheep. AB - Pregnancy in humans is associated with a number of physiologic changes including interstitial fluid retention (edema) and a decrease in the systemic vascular response to infused angiotensin II. In nonpregnant sheep angiotensin II increases the lymph flow rate by what appears to be a direct effect on the lymphatic vessels. The purpose of this study was to test the hypothesis that during pregnancy the lymph flow rate response to angiotensin II infusion is decreased in relation to that of the nonpregnant state. We speculate that a decrease in lymph flow may explain the interstitial fluid retention observed during human pregnancy. In nine nonpregnant and five pregnant chronically catheterized ewes, we infused angiotensin II at rates of 0.1, 10, and 1000 ng/kg/min during a 5 minute period, with intervals of at least 15 minutes between doses. At the highest angiotensin II dose, peak lymph flow rate increased 286% in pregnant ewes compared with an increase of 344% in the nonpregnant sheep (p less than 0.05). No changes occurred in the intravascular volume, plasma or lymph protein concentration, or venous pressure. The arterial pressure responses to angiotensin II were decreased in pregnant sheep (p less than 0.05). These results are compatible with a model for fluid retention in pregnancy in which a decreased lymph flow rate plays a significant role in interstitial fluid retention. PMID- 2603920 TI - Is a decrease in plasma oncotic pressure enough to explain the edema of pregnancy? AB - The balance of fluid across capillaries is given by the Starling equation. Because the plasma protein concentration (one of its components) is decreased in pregnancy, we decided to explore the question as to whether hypoproteinemia with intact protein mass (produced by blood volume expansion) or hypoproteinemia with decreased total protein mass (produced by removal of circulating proteins) alters the oncotic pressure differences across capillaries. We calculated the oncotic pressure difference obtained in seven nonpregnant ewes during periods of normoproteinemia and hypoproteinemia; the influence of fluid infusion under both conditions was also observed. There was an increase in the oncotic pressure difference across the capillary wall during hypoproteinemia produced by a decrease in the total protein mass (p less than 0.01); however, the response to hypoproteinemia produced by fluid infusion was similar (p greater than 0.1). The venous pressure (used as an index of interstitial fluid pressure changes) did not differ in either hypoproteinemia or fluid infusion. Capillary permeability was decreased during hypoproteinemia, as evidenced by a higher lymph/protein ratio of labeled albumin during the control period (p less than 0.05). In conclusion, during a state of decreased plasma protein concentration similar to that of pregnancy, the difference in the oncotic pressure and hydrostatic pressure forces acting to prevent transfer of fluid to the interstitium is increased. Therefore other factors that influence fluid transfer across the capillaries must be investigated to explain the edema of pregnancy. PMID- 2603921 TI - The antagonistic effect of oxytocin and relaxin on rat uterine segment contractility. AB - To test the interaction of various hormones on the myometrium, the following experiments were done studying in vitro contractile activity of uterine segments from immature rats. The rats were divided into two groups: group 1 animals were treated with estrogen (n = 9) and group 2 animals were treated with both estrogen and progesterone (n = 11). Uteri from animals in each group were removed and segments were maintained in a temperature- and pH-controlled organ bath. After baseline contractions were established, uterine segments were treated with either oxytocin and then relaxin, or relaxin and then oxytocin. The dose of relaxin used, 20 ng/ml, was previously shown to be effective in inhibiting uterine contractions of animals treated with either estrogen or estrogen plus progesterone. The dose of oxytocin, 2.5 mlU/ml, was the maximal effective dose shown not to produce prolonged tetany. Estrogen plus progesterone treatment increased the frequency of contractions and resulted in contractions of greater duration of the maximal contractile force, as compared with treatment with estrogen alone. Oxytocin caused a stimulation of contractions in relaxin inhibited uterine strips. Relaxin decreased the hypertonic contractions produced by oxytocin treatment, resulting in contractions similar to baseline. These data demonstrate that oxytocin and relaxin are directly antagonistic in their effects on uterine contractility. This suggests that labor may occur as a result of increased sensitivity to oxytocin or a decreased sensitivity to relaxin. PMID- 2603922 TI - Decreased beta-carotene tissue levels in uterine leiomyomas and cancers of reproductive and nonreproductive organs. AB - The dietary importance of beta-carotene as a factor in health maintenance has recently attracted considerable interest. Previously, total carotene content was estimated in a limited number of human tissues by means of spectrophotometric methods. In this study the levels of beta-carotene were measured by high-pressure liquid chromatography in tissue samples of uterine leiomyomas and adjacent normal myometrium obtained at hysterectomy from uteri of 18 patients. beta-Carotene concentration was significantly (p = 0.0013) lower in fibroid tissue than in normal myometrium. In addition, levels of beta-carotene were assayed in tissue samples of cancers of the cervix, endometrium, ovary, breast, colon, lung, liver, and rectum and were compared with levels of respective adjacent normal sites. The concentrations of beta-carotene were found to be lower in all cancer tissues. The decreased levels of beta-carotene suggest that beta-carotene deficiency may have a role in the cause and/or pathogenesis of leiomyomas and cancers of the organs that were investigated. The mechanism of action, however, remains unknown. PMID- 2603923 TI - Assessment of epidermal growth factor in the healing process of clean full thickness skin wounds. AB - Epidermal growth factor is a potent stimulant of epithelialization. However, the usefulness of topical applications of epidermal growth factor in accelerating wound healing in full-thickness skin wounds with a large panniculus adiposus has not been clear. Four full-thickness skin incisions were made in the back of 10 female pigs that treated twice a day for 14 days with 2 ml of epidermal growth factor (300 ng/ml) or 2 ml of Ringer's lactate solution in a single-blind, randomized fashion. Two pigs received only epidermal growth factor, two pigs received only Ringer's lactate solution, and six pigs were treated with both solutions. The original skin plug was weighed to ensure similarity of groups. Photographs and measurements of each incision were taken every 7 days. The mean surface areas of the incisions treated with epidermal growth factor were 8.45, 7.50, and 2.30 cm2; in the incisions treated with Ringer's lactate solution the measurements were 8.42, 8.16, and 2.37 cm2 on observation days 1, 7, and 14, respectively. Although a trend toward a faster healing rate was noted in the incisions treated with epidermal growth factor, this difference was not statistically significant. With the doses and the time interval used between treatments, minimal benefit was obtained with epidermal growth factor when compared with Ringer's lactate solution. PMID- 2603924 TI - Spontaneously resorbing ectopic pregnancy: preservation of human chorionic gonadotropin bioactivity despite declining steroid hormone levels. AB - We compared serum hormone profiles of patients with normal intrauterine pregnancies (n = 14), spontaneously resorbing ectopic pregnancies (n = 10), and viable ectopic pregnancies (n = 26). Hormone profiles were evaluated at 5 to 8 weeks' gestational age. Ectopic pregnancies were diagnosed by laparoscopy; intrauterine gestations were confirmed by ultrasonography. Immunoreactive beta human chorionic gonadotropin, progesterone, estradiol, and 17-hydroxyprogesterone were measured by radioimmunoassay. Bioactive human chorionic gonadotropin was measured by a modified mouse Leydig cell bioassay. Diminished steroid production was noted in ectopic pregnancies; levels in serum of patients with resorbing ectopic pregnancies were lower than values expressed in viable ectopic pregnancies (p less than 0.01). Serum levels of human chorionic gonadotropin bioactivity correlated closely with immunoreactive human chorionic gonadotropin in all three groups (r = 0.81, p less than 0.01). Ratios of bioactive human chorionic gonadotropin to immunoreactive beta-human chorionic gonadotropin were similar (0.93 +/- 0.26 in resorbing ectopic pregnancies, 1.11 +/- 0.16 in viable ectopic pregnancies, and 0.90 +/- 0.10 in intrauterine pregnancies). We conclude that although reduced serum levels of steroids noted in ectopic pregnancy suggest an impairment in corpus luteum activity, diminished steroid production was not attributable to lower human chorionic gonadotropin bioactivity. PMID- 2603925 TI - Decreased in vitro production of 6-keto-prostaglandin F1 alpha by uterine arteries from postmenopausal women. AB - Cessation of ovarian function is associated with a marked increased in morbidity and mortality secondary to ischemic heart disease. Estrogen replacement has been shown to impart protection against ischemic heart disease. We hypothesized that estrogen may influence vascular production of vasodilators such as prostacyclin. To investigate this relationship we have measured the production of 6-keto prostaglandin F1 alpha, and thromboxane B2 by superfused uterine arteries from pre- and postmenopausal women. Arterial specimens from healthy normotensive premenopausal (n = 5) and postmenopausal women (n = 5) were superfused for 5 hours. Production of 6-keto-prostaglandin F1 alpha reached steady state levels by 120 minutes and remained linear for the length of the experiment. Indomethacin (4 x 10(-5) mol/L) added at 120 minutes significantly decreased prostanoid production. In subsequent experiments, 17 beta-estradiol in concentrations of 10, 100, 1000 ng/ml was added to the superfusion media at 120 minutes. Total production of 6-keto-prostaglandin F1 alpha by premenopausal arteries superfused with neat media during the steady state interval (3 hours) was significantly greater than that of postmenopausal specimens (1.25 versus 0.27 ng/mg dry tissue, p less than 0.05). Thromboxane B2 levels were undetectable in spent media. However, the addition of 17 beta-estradiol did not alter production of 6-keto prostaglandin F1 alpha. These data suggest that arterial production of prostacyclin is significantly decreased in uterine arteries from postmenopausal women, but in this in vitro model system estrogens did not affect vascular prostanoid production. PMID- 2603926 TI - Depressive episodes in premenstrual syndrome. AB - Episodic depression, a prominent but poorly defined symptom of premenstrual syndrome, was quantitated in 24-hour cortisol secretory episodes (determined by sampling at 20-minute intervals) as biochemical markers, as well as the Beck Depression Inventory and Profile of Mood States as psychometric measures. Results of 16 patients with premenstrual syndrome were compared with six age-matched women with endogenous depression and 16 control women. On both the Profile of Mood States and Beck Depression Inventory, women with premenstrual syndrome showed a marked worsening of scores (p less than 0.01) during the luteal phase compared with either their own follicular phase scores or the scores of controls in either cycle phase. However, Beck Depression Inventory scores were threefold higher (p less than 0.005) in women with depression than in those with luteal phase premenstrual syndrome (3.37 +/- 3.6 vs. 11.9 +/- 2.5). The Profile of Mood States depression scale was also higher (p less than 0.05) in women with depression than in those with premenstrual syndrome, while scores on other Profile of Mood States scales were similar. The numbers of cortisol secretory pulses identified by the cluster algorithm were similar (5 to 6 per 24 hours) in all groups, and the time of circadian nadirs as determined by cosinor rhythmometry were comparable. While the mean amplitude and duration of the cortisol pulses were also similar in women with premenstrual syndrome and controls, both were significantly higher (p less than 0.05) in women with depression. This resulted in markedly enhanced (p less than 0.005) cortisol secretion during a given secretory episode in women with depression and in higher 24-hour transverse mean cortisol values in women with depression (87.8 +/- 5.8 ng/ml) than in either those with premenstrual syndrome (66.7 +/- 3.3 ng/ml) or controls (58.9 +/- 3.3 ng/ml). These data affirm the clinical impression that depressive episodes occurring selectively in the luteal phase of the cycle in women with premenstrual syndrome are not present in controls and demonstrate, for the first time, that these episodes are distinct from endogenous depression as measured by both cortisol secretory parameters and psychological indices. PMID- 2603927 TI - Peri-implantation phase endometrial estrogen and progesterone receptors: effect of ovulation induction with clomiphene citrate. AB - The effects of clomiphene citrate on endometrial nuclear estradiol receptors and progesterone receptors were examined in 10 normal women during an untreated cycle (control) and during treatment with 50 mg clomiphene citrate and 150 mg clomiphene citrate daily on days 5 through 9. Concentrations and binding constants of the receptors were determined in endometrium obtained 8 to 12 days after midcycle luteinizing hormone surge. Scatchard plots for both estrogen receptors and progesterone receptors were linear, indicating only one type of high-affinity binding sites. In control cycles, estrogen receptor levels (mean +/ SEM) were 199.6 +/- 23.1 fmol/mg deoxyribonucleic acid, (n = 8) and were not significantly different from either 50 mg clomiphene citrate (180.5 +/- 19.1 fmol/mg deoxyribonucleic acid, n = 6) or 150 mg clomiphene citrate (194.3 +/- 35.2 fmol/mg deoxyribonucleic acid, n = 4). Similarly, the dissociation constants were unaffected by clomiphene citrate treatment. The concentrations of progesterone receptors in the control cycles (613 +/- 31 fmol/mg deoxyribonucleic acid, n = 5) and treatment cycles (50 mg clomiphene citrate -652.8 +/- 121 fmol/mg deoxyribonucleic acid, n = 6; 150 mg clomiphene citrate -592.6 +/- 31 fmol/mg deoxyribonucleic acid, n = 7) were also not significantly different. Clomiphene citrate also did not affect dissociation constants for progesterone receptors. Therefore, ovulation induction with clomiphene citrate apparently did not affect peri-implantation phase endometrial estrogen receptors and progesterone receptors or their respective binding constants. PMID- 2603928 TI - Aromatase in human fetal tissues. AB - The placenta has been shown to be the major source of estrogen production during pregnancy. This investigation was undertaken to compare the content and activity of aromatase in the placenta and various other human fetal tissues. Tissues were obtained from first- and second-trimester human abortuses. The amount of aromatase P-450 (aromatase cytochrome P-450) in tissue homogenates was determined after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting by use of a polyclonal antibody directed against aromatase cytochrome P-450. The activity of aromatase in microsomal preparations was assayed by determining the rate of incorporation of tritium from 1 [3H]androstenedione into [3H]water. The greatest amount of aromatase cytochrome P 450 (55 kd) was detected in placenta and lesser amounts were detected in other tissues. Aromatase activity also was highest in placental microsome fractions (368 +/- 62.4 pmol/mg/hr [mean +/- SE], n = 9). A significant amount of aromatase activity was also detected in fetal liver (19 +/- 4.8 pmol/mg/hr, n = 7). Much less activity was found in brain (2.8 +/- 1.0 pmol/mg/hr, n = 6) and intestine (2.7 +/- 1.3 pmol/mg/hr, n = 7). Minimal activity was noted in adrenal (n = 5), spleen (n = 4), stomach (n = 4), and muscle (n = 5) (1.2 to 1.5 pmol/mg/hr). Activity in kidney (n = 7), heart (n = 4), and lung (n = 4) was extremely low (less than 0.8 pmol/mg/hr). In conclusion, the placenta is a major site of conversion of C19 steroid precursors to estrogens because of the amount of enzyme and the high rate of activity of aromatase compared with those of other fetal tissues. However, considering the size and rate of aromatase activity in other fetal tissues such as liver, brain, and intestine, these tissues also may contribute to the total estrogen production in the fetal-placental unit. PMID- 2603929 TI - Comparison of in vivo bioavailability of progestational agents into the rat uterus and liver and the effect of plasma protein binding. AB - The in vivo bioavailabilities of three clinically available progestational agents were evaluated with a previously described rat model. With this model a single injection, double-isotope technique was performed to calculate and compare the unidirectional extractions of progesterone, 19-nortestosterone, and medroxyprogesterone acetate into the rat uterus and liver. To assess the role of plasma protein binding in the extraction of these agents, steroids were presented in four different vehicles: (1) Ringer's solution, 0.1% bovine serum albumin; (2) Ringer's solution, 4% bovine serum albumin; (3) Ringer's solution, 0.8 mg/ml, alpha 1-acid glycoprotein; (4) human pregnancy serum. The results revealed that liver extraction always exceeded uterine extraction for each progestin, regardless of the vehicle, and that liver extraction was approximately 100% for all steroids. With regard to the uterus, when binding proteins were not present in the injectate, the extraction of the three steroids was similar; the uterine vasculature was relatively permeable to these progestins, and bovine serum albumin and alpha 1-acid glycoprotein had no major effect on the uptake into the uterus. However, when human pregnancy serum was in the injectate, the extractions of progesterone and 19-nortestosterone into the rat uterus were significantly diminished. In contrast, pregnancy serum had no effect on the uptake of medroxyprogesterone acetate into the uterus, with the extraction equal to that of Ringer's solution alone. This suggests that, regardless of potential binding proteins, medroxyprogesterone acetate displays greater bioavailability than that of the other progestogens studied. PMID- 2603930 TI - In vivo administration of allopurinol affects ovulation and early embryonic development in rabbits. AB - The potential role of the hypoxanthine-xanthine oxidase system in human chorionic gonadotropin-induced ovulation, nuclear maturation, and preimplantation development was investigated in the rabbit by use of the xanthine oxidase inhibitor allopurinol. Allopurinol (50 mg/kg) or vehicle was injected, followed by human chorionic gonadotropin (100 IU). Administration of inhibitor or vehicle was repeated 3 hours later. Ovaries and ovulated ova were inspected 12 or 24 hours after human chorionic gonadotropin administration for follicle rupture, cumulus dispersal, and nuclear maturation. Ova were inseminated in vitro and assessed for development to the blastocyst stage, up to 96 hours after insemination. Allopurinol significantly reduced ovulatory efficiency, defined as the percent of large follicles that ovulate, and decreased the percent of ova with cumulus dispersal. Allopurinol significantly inhibited morula and blastocyst formation. These data suggest that the xanthine oxidase system may play a role in ovulation and early embryonic development. PMID- 2603931 TI - Effects of platelet activating factor on mouse oocyte fertilization in vitro. AB - Platelet activating factor is rapidly gaining acceptance as a potent mediator in many reproductive processes. This study presents data that indicate a direct role of platelet activating factor in fertilization. Platelet activating factor was shown to significantly increase (p less than 0.001) the fertilization rate of mouse oocytes in vitro. Furthermore, CV3988, an inhibitor of platelet activating factor, was noted to significantly decrease in vitro fertilization rates at 10( 5) and 10(-4) mol/L concentrations. PMID- 2603932 TI - Release of tumor necrosis factor-alpha by human peritoneal macrophages in vivo and in vitro. AB - Tumor necrosis factor is a product of activated monocytes, macrophages, and lymphocytes that exerts a variety of effects in the host. Its cytotoxicity toward gametes has been suggested as a mechanism of how activated macrophages may cause subfertility, inasmuch as detectable levels of tumor necrosis factor have been reported in the peritoneal fluid of infertile patients. To further examine this issue we measured tumor necrosis factor activity in peritoneal fluid and its release in vitro from monocytes or peritoneal macrophages of patients undergoing laparoscopy because of either tubal ligation or infertility. Cytolytic activity was determined with a bioassay with sensitized mouse fibrosarcoma cells as target. Significant tumor necrosis factor activity (greater than 5 U/ml) was detected in 38% of the peritoneal fluid samples. A total of 43% of the peritoneal macrophage samples released significant tumor necrosis factor activity in vitro and all samples tested including peripheral monocytes released high levels of activity in the presence of bacterial endotoxin. The activity was released in vitro in a time-dependent manner. Thermal stability characteristics and neutralization with a specific antibody indicated that most of the activity in peritoneal fluid or released in vitro was that of tumor necrosis factor-alpha. Statistical analysis of tumor necrosis factor activity in peritoneal fluid in various diagnostic categories revealed a significantly elevated level in patients with endometriosis, as compared with fertile women. Endometriosis and pelvic adhesions were also significantly more likely to be associated with measurable levels of tumor necrosis factor activity released by peritoneal macrophages in vitro. Overall, because tumor necrosis factor-alpha levels were frequently detectable, it suggests that activation of peritoneal macrophages either by bacterial products or inflammatory conditions can occur in vivo. Moreover, these cells remain competent to release tumor necrosis factor in vitro. PMID- 2603933 TI - Isolation and sequencing of a complementary deoxyribonucleic acid clone encoding human placental 17 beta-estradiol dehydrogenase: identification of the putative cofactor binding site. AB - 17 beta-Estradiol dehydrogenase (EC 1.1.1.62) catalyzes the interconversion of estradiol and estrone in human term placenta. We have raised a specific polyclonal antibody to this abundant placental enzyme to study its role in late pregnancy events and its molecular biologic characteristics. In this work the 17 beta-estradiol dehydrogenase antibody was used to isolate and sequence a complementary deoxyribonucleic acid clone encoding about 98% of the amino acid sequence of the 17 beta-estradiol dehydrogenase molecule. This sequence verifies previous sequence data on the molecule's steroid binding site and also localizes a putative nicotinamide adenine dinucleotide binding region similar to that of many other pyridine nucleotide-dependent dehydrogenases. Isolation of the complementary deoxyribonucleic acid for 17 beta-estradiol dehydrogenase expands our knowledge of the structure-function relationships of the enzyme and is a major step in our understanding of its biologic function in pregnancy. PMID- 2603934 TI - Molecular scanning of Yq11 (interval 6) in men with Sertoli-cell-only syndrome. AB - Data suggesting that probes pDP105/B and 50f2/C,E may identify sequences on distal Yq11 (interval 6) that are critical for spermatogenesis stimulated a study of this region by means of these two probes in azoospermic 46,XY men with biopsy proved Sertoli-cell-only syndrome. Deoxyribonucleic acid samples from controls and study subjects were digested with the restriction enzymes TaqI, EcoRI, and BamHI. These samples were blotted and hybridized with pDP105/B, 50f2/C,E, and two more proximal Yq11 probes 4B-2 and pAS1. The sequence hydridizing to 50f2/C was absent in one study subject. No deletions were detected with pDP105/B and the two more proximal probes. PMID- 2603935 TI - Fetomaternal hemorrhage--possible cause of fetal distress and death. PMID- 2603937 TI - Pulmonary artery agenesis. PMID- 2603936 TI - Dosage and duration differences lead to diverse conclusions. PMID- 2603938 TI - Other routes charted after description of adventurous journey of CA 125. PMID- 2603940 TI - Techniques differ in use of Doppler ultrasonography. PMID- 2603939 TI - Perinatal death as a result of social factors. PMID- 2603941 TI - Results of uterine activity studies in agreement, but methods differ. PMID- 2603943 TI - Interdisciplinary review of estrogen replacement therapy. PMID- 2603942 TI - Effect of magnesium and preeclampsia on plasma cholinesterase activity. PMID- 2603944 TI - Estrogen replacement therapy: what the future holds. AB - Although hormonal replacement therapy has proved beneficial for many postmenopausal women, several issues remain to be resolved through future research. Improved combination therapy, better delivery systems, and optimal dosing may enhance compliance, which is essential for maximum benefit from therapy. Epidemiologic studies are necessary to clarify the role of estrogen in osteoporosis and cardiovascular disease. Additionally, the contribution of hormonal replacement therapy to the development of breast and endometrial cancers needs to be clarified. PMID- 2603945 TI - Occupational therapy in early intervention: new perspectives create greater possibilities. PMID- 2603946 TI - Olduvai Hominid 7 trapezial metacarpal 1 articular morphology: contrasts with recent humans. AB - A consideration of the metacarpal 1 articulation of the Olduvai Hominid 7 trapezium shows that, although it is generally similar to those of recent humans, it is considerably flatter radioulnarly and dorsopalmarly than those of modern humans and similar in its degree of dorsopalmar flattening to those of Upper Pleistocene late archaic humans. Even though this flattening may have slightly limited flexion-extension at the pollical carpometacarpal joint, it is most likely related to the apparently elevated levels of axial joint reaction force through the thumbs of archaic members of the genus Homo. It also documents the continuation of human carpometacarpal articular evolution through the Pleistocene. PMID- 2603947 TI - Endocranial suture closure in rhesus macaques (Macaca mulatta). AB - Endocasts from skulls of 330 rhesus monkeys (Macaca mulatta) of known age are scored for closure of nine bilateral and three unilateral sutures or segments of sutures. A variety of tests reveals a strong relationship between age and stages of suture closure, although increasingly broad confidence intervals prevent sutures from being very useful for precisely aging older macaques. The order in which endosutures begin to close, as well as that in which closure is finally achieved, is determined for macaques, and these sequences compared to those for endosutures of humans (Todd and Lyon, 1924). The basilar suture is the earliest to close, while the masto-occipital and rostral and caudal squamosal sutures achieve closure quite late in both species. On the other hand, humans and macaques differ in their schedules for the sphenofrontal suture and in the initiation of closure for the rostral portion of the squamosal suture. Two sutures close significantly sooner on the right than on the left side (the rostral squamosal and masto-occipital) and asymmetry favoring closure of the right lateral lambdoid suture also approaches significance at the 0.05 level. No sutures close significantly sooner on the left side. It is suggested that macaque sutures may close from the inside out, that endosutures are more sensitive than ectosutures for detecting sequences in which cranial sutures begin to close, and that directional asymmetries in suture closure of macaques may be related to minor asymmetries in brain/skull shape (petalias). PMID- 2603948 TI - Relationships between the size and spatial morphology of human masseter and medial pterygoid muscles, the craniofacial skeleton, and jaw biomechanics. AB - The relationship between human craniofacial morphology and the biomechanical efficiency of bite force generation in widely varying muscular and skeletal types is unknown. To address this problem, we selected 22 subjects with different facial morphologies and used magnetic resonance imaging, cephalometric radiography, and data from dental casts to reconstruct their craniofacial tissues in three dimensions. Conventional cephalometric analyses were carried out, and the cross-sectional sizes of the masseter and medial pterygoid muscles were measured from reconstituted sections. The potential abilities of the muscles to generate bite forces at the molar teeth and mandibular condyles were calculated according to static equilibrium theory using muscle, first molar, and condylar moment arms. On average, the masseter muscle was about 66% larger in cross section than the medial pterygoid and was inclined more anteriorly relative to the functional occlusal plane. There was a significant positive correlation (P less than 0.01) between the cross-sectional areas of the masseter and medial pterygoid muscles (r = 0.75) and between the bizygomatic arch width and masseter cross-sectional area (r = 0.56) and medial pterygoid cross-sectional area (r = 0.69). The masseter muscle was always a more efficient producer of vertically oriented bite force than the medial pterygoid. Putative bite force from the medial pterygoid muscle alone correlated positively with mandibular length and inversely with upper face height. When muscle and tooth moment arms were considered together, a system efficient at producing force on the first molar was statistically associated with a face having a large intergonial width, small intercondylar width, narrow dental arch, forward maxilla, and forward mandible. There was no significant correlation between muscle cross-sectional areas and their respective putative bite forces. This suggests that there is no simple relationship between the tension-generating capacity of the muscles and their mechanical efficiency as described by their spatial arrangement. The study shows that in a modern human population so many combinations of biomechanically relevant variables are possible that subjects cannot easily be placed into ideal or nonideal categories for producing molar force. Our findings also confirm the impression that similar bite-force efficiencies can be found in subjects with disparate facial features. PMID- 2603949 TI - Hamann-Todd Collection aging studies: osteoporosis fracture syndrome. AB - The study presents a retrospective analysis of distal radius, proximal femur, vertebral, and sacral fractures that occurred in 938 Hamann-Todd Collection skeletons. Individuals included in the investigation were retrieved from dissecting room cadavers in Cleveland, Ohio, between the years 1910 and 1940. Demographic analysis showed that the mean ages at death for blacks and whites included in the study were 41.9 and 53.8 years, respectively. Evaluations of fracture repair status were made for all fractures that were identified. Observations that document side of involvement and unilateral/bilateral distribution were made for distal radius and hip fractures. It was found that the age-, sex-, and race-related fracture patterns which characterize the early 20th century Hamann-Todd sample strongly correspond in distribution and magnitude to those seen in modern American and European urban industrial communities. The distal radius, hip, vertebral, and sacral fractures which were identified in individuals over 60 years of age appear to be a primary result of skeletal fragility due to age progressive bone loss. However, it is suggested that the early onset and high frequency of distal radius fractures seen in climacteric Caucasian women may be more directly due to accidental falls initiated by a greater frequency, intensity, and duration of vasomotor disturbances which are known to accompanay estrogen withdrawal in perimenopausal white females. PMID- 2603950 TI - Inbreeding effects on fetal growth in Beirut, Lebanon. AB - Effects of consanguineous marriages on offspring's gestational age and anthropometrics at birth were investigated in Beirut through a hospital-based survey of 1,252 newborns. Twenty-five percent of all newborns were inbred, and the mean inbreeding coefficient was 1.25%. Neither prematurity rate nor weight, length, head circumference, and chest circumference (considered individually, or as a whole) showed a significant pattern by type of parental consanguinity. Failure to demonstrate significant inbreeding effects is reported in several other studies and generally interpreted as the long-term result of continued inbreeding practices. PMID- 2603951 TI - Meaning of biodistance statistics: a test case using adult monozygotic twins. AB - Anthropometry, historically one of the primary research techniques in physical anthropology, has been widely utilized in biodistance studies. The complex genetic and environmental interaction that governs the expression of anthropometric dimensions, together with concerns over measurement error, have sometimes clouded the interpretation of biodistances based upon anthropometry. In this study, 51 pairs of adult monozygotic twins were analysed using discriminant analysis and Mahalanobis' generalized distance. Both male and female twins, grouped by first- versus second-born, displayed very small, statistically insignificant distances between groups. When literature estimates of intra observer measurement errors were used as a frame of reference, the average absolute differences between the twin pairs were approximately twice the size of the measurement error estimates. The results of this study suggest that, first, the environmental effect upon the genetically influenced traits measured by anthropometry is not large enough to bring about significant multivariate differences between identical twin pairs; and, second, biodistance studies based upon anthropometry can be reliable so long as measurement error is minimized. PMID- 2603952 TI - Low-dose glucocorticoids stimulate electroneutral NaCl absorption in rat colon. AB - Glucocorticoids, not aldosterone, may regulate basal colonic NaCl transport. Aldosterone induces spironolactone-inhibitable, amiloride-inhibitable conductive Na absorption but basal transport is electroneutral and amiloride and spironolactone resistant. We examined in vivo the Na absorptive pathway induced by glucocorticoid receptor specific doses of glucocorticoid using various amiloride analogues. Doses of dexamethasone sufficient to co-occupy aldosterone receptors produced amiloride-sensitive Na absorption in proximal and distal colon. Low doses of dexamethasone or the specific glucocorticoid RU26988 markedly stimulated Na absorption but did so by an amiloride-resistant mechanism. The Na-H antiport inhibitor, 5-N-ethyl-N-isopropylamiloride (NENIA) eliminated glucocorticoid-induced Na and Cl absorption without changing transmural potential difference (PD) in proximal and distal colon (Ki = 0.7 x 10(-7) M). NENIA had no effect on aldosterone-induced transport. NENIA (10(-5) M) almost eliminated Na absorption in adrenal intact animals if infused early in the experimental protocol. With time, NENIA resistance developed, corresponding with the previously documented rise in endogenous aldosterone. Thus glucocorticoids induce an electroneutral Na absorptive pathway that may be the luminal Na-H antiport, suggesting that glucocorticoids regulate adrenal-dependent electroneutral Na absorption in rat colon. PMID- 2603953 TI - Isolation of mutant renal (LLC-PK1) epithelia defective in basolateral, Na(+) independent glucose transport. AB - To obtain mutant renal epithelia defective in the uptake of 2-deoxyglucose (Na(+) independent glucose transport), LLC-PK1 renal epithelial cells were subjected to a combination of DNA alkylation, tritium-suicide with 2-[3H]deoxyglucose, and replica plating. One of the mutant sublines obtained, LLC-PK1M-7A, possesses only 40% of the 2-deoxyglucose uptake rate of the parent line, LLC-PK1M, and this defect is stable over at least 30 population doublings. Initial rate of 3-O methylglucose transport into these mutant cells is only 20% of the parental rate, and efflux of 3-O-methylglucose from the mutant cells is correspondingly low. Glucose metabolism in the mutant cells does not appear to be altered, nor is free glucose accumulated in the cells against a concentration gradient. The uptake rate of L-leucine is the same in both mutant and parent, whereas the (Na(+) dependent) uptake of alpha-methyl-D-glucoside and methylaminoisobutyric acid is greater in the mutant than the parent. The population doubling times of LLC-PK1M and LLC-PK1M-7A cultures are similar. LLC-PK1M-7A cell morphology is similar to LLC-PK1M when cultures are subconfluent, but on reaching confluence, LLC-PK1M-7A appear larger than LLC-PK1M cells. Their measured cell volume is then 150% of the volume of the parent cells. Future studies of the LLC-PK1M-7A mutant, and acquisition of additional mutant sublines, should elucidate the roles of transepithelial glucose transport in proximal tubular cell physiology. PMID- 2603954 TI - Epidermal growth factor receptor regulation in rat kidney: two models of renal growth. AB - The binding of 125I-labeled epidermal growth factor (EGF) to plasma membranes prepared from rat kidney cortex was studied following unilateral nephrectomy, a model of proximal tubule cell hypertrophy, and following the administration of folic acid, a model of proximal tubule cell hyperplasia. Binding of 125I-EGF was a linear function of basolateral membrane protein content and time of incubation. Specific binding to luminal brush-border membranes was not evident in these studies. Neither insulin nor insulin-like growth factor I could displace EGF binding, indicating that binding was specific. Scatchard analysis revealed a single binding site. The KD in sham-operated animals 48 h after surgery was 11.2 +/- 1.4 nM, whereas Bmax averaged 95.2 +/- 4.1 fmol/mg protein (n = 3). Similar values were obtained in nephrectomized animals. The Bmax of folic acid-untreated animals averaged 212.5 +/- 6.9 fmol/mg 48 h after administration, whereas that of vehicle-injected controls averaged 85.4 +/- 9.2 (n = 3, P less than 0.001). Differences in binding were not related to changes in affinity, ligand degradation by the preparations, or receptor binding of endogenous EGF. These data indicate that regeneration following folic acid administration is associated with an upregulation of proximal nephron EGF receptors that may play an important role in the mitogenic response. PMID- 2603955 TI - Evidence that alteration of charge modifies proximal tubular shunt pathway permselectivity. AB - Experiments were performed to test the hypothesis that membrane charge is an important determinant of paracellular pathway ion permselectivity in the proximal tubule. Net negative charge in or around the paracellular pathway should favor cation permeability; net positive charge should favor anion permeability. Therefore compounds such as amiloride and 4-acetamido-4'-isothiocyanostilbene 2,2'-disulfonic acid (SITS), capable of changing net membrane charge, should predictably change the diffusive permselectivity of the paracellular pathway to anions and cations. In the first group of experiments amiloride, a compound capable of increasing net positive membrane charge, inhibited cation and enhanced anion diffusive permeability. In a second group of experiments, SITS, a compound capable of increasing net negative membrane charge, inhibited anion and enhanced cation diffusive permeability. The effects of amiloride and SITS were symmetrical; the lumen-to-bath and the bath-to-lumen diffusion potentials were not significantly different in magnitude. In addition these effects were completely and rapidly reversible. Our results suggest that amiloride increases net positive charge, and SITS increases net negative charge within the paracellular pathway. The most likely site for the actions of SITS and amiloride is the tight junction because the effects of the inhibitors were symmetrical. Both compounds act at low concentrations and reversibly such that removal of the inhibitor rapidly reverses its effects. We propose, on the basis of the ease with which these alterations in charge and thus paracellular pathway permselectivity occurred, that the permselectivity of this pathway may not be fixed and constant for any given proximal tubular segment. In fact, permselectivity may vary and thus serve as an important physiological control mechanism for proximal tubular solute and water reabsorption. PMID- 2603956 TI - A D-mannose transport system in renal brush-border membranes. AB - Dog renal brush-border membrane vesicles (BBMV) from whole kidney cortex contain both low-affinity, high-capacity and high-affinity, low-capacity Na-dependent D glucose cotransporters. D-Mannose is an epimer of D-glucose, differing in structure only in the axial, rather than equatorial, orientation of the hydroxyl group at the C-2 position of the pyranose ring. Uptake experiments of radioactive sugars into BBMV by standard Millipore filtration were performed to determine whether D-mannose shares either, or both, of the D-glucose carriers or if it is transported by an independent system. Transport of D-mannose occurs into an osmotically active space and is saturable and sodium dependent with a 1:1 Na:D mannose stoichiometry, Km of 0.063 mM, Vmax of 3.6 nmol.mg-1.min-1, 25 degrees C, and pH 7.4. When an NaSCN electrochemical gradient was present, an "overshoot" was present, indicating active cotransport. Up to 50 mM D-mannose did not inhibit sodium-dependent D-glucose or alpha-methylglucoside uptake (0.01-20 mM). Sodium dependent D-mannose uptake was inhibited by the following compounds in order of decreasing effectiveness: fructose greater than mannoheptulose greater than 2 deoxy-D-glucose greater than 2-fluoro-2-deoxy-D-glucose much greater than phloretin, cytochalasin B, galactose, 3-O-methyl-D-glucose, and L-mannose. Phlorizin also inhibited D-mannose uptake, but the high concentration required and the fact that a competitive pattern of inhibition could not be demonstrated contrasted with its effect on D-glucose transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2603957 TI - Characterization of the major brain osmolytes that accumulate in salt-loaded rats. AB - Previous studies demonstrated an accumulation of "idiogenic osmoles" in the brain with chronic salt loading. Amino acids are known to constitute a portion of these solutes, but the balance of the solutes has yet to be fully characterized. In the present study, 1H-nuclear magnetic resonance (NMR) spectroscopy and biochemical assays of rat brain were used to identify and quantify changes in organic solutes in two different animal models of hypernatremia: hypertonic salt loading and water deprivation. Five days of salt loading increased plasma sodium concentration (PNa) to 165 meq/l and 3 days of water deprivation increased PNa to 151 meq/l, compared with 141 meq/l in controls. Amino acids, methylamines, and polyols were all significantly higher in salt-loaded animals compared with controls. Specifically, higher contents of glutamine (+65%), glutamate (+27%), myo-inositol (+36%), phosphocreatine + creatine (PCr + Cr) (32%), glycerophosphorylcholine (GPC) (+75%), and choline (+114%) were observed. Sorbitol and betaine, osmolytes known to accumulate in the hypertonic inner medulla, were present in low amounts in the brain and were unchanged with salt loading. In contrast to the results with salt loading, no accumulation of brain organic solutes was detected after 3 days of water deprivation. Based on these findings, we propose that amino acids, methylamines, and polyols function as osmoregulatory solutes in the brains of salt-loaded rats in a manner similar to that observed in other biological systems, whereas 3 days of water deprivation is an insufficient stimulus for their accumulation. PMID- 2603958 TI - Methylamine and polyol responses to salt loading in renal inner medulla. AB - Methylamines and polyhydric alcohols (polyols) are major organic osmolytes of the mammalian renal inner medulla and have generally been noted to change in parallel with urine osmolality. In the present study, responses of inner medullary methylamines and polyols to 5 days of salt loading were investigated. Salt loading increased plasma sodium concentration and induced a saline diuresis that resulted in a significantly lower urine osmolality (Uosmol) in salt-loaded rats (1,246 mosmol) compared with controls (2,147 mosmol). Analysis of inner medullary organic osmolytes using 1H-NMR spectroscopy and biochemical assays indicated no significant change in total methylamines, total polyols, or total osmolytes with salt loading. However, there were marked changes in individual organic osmolytes. Renal inner medullary glycerophosphorylcholine (GPC) was 41% lower in salt-loaded rats, and was the only organic osmolyte that changed in parallel with Uosmol, which was 42% lower in this group. In contrast, glycine betaine (betaine) and sorbitol contents were elevated by 286% and 33%, respectively, with salt loading, and myo-inositol (inositol) was unchanged. These findings indicate selective renal inner medullary osmolyte responses to salt loading with only GPC varying directly with changes in urine osmolality. PMID- 2603959 TI - Immediate and long-term effects of pregnancy on glomerular function in the SHR. AB - Micropuncture experiments investigated 1) whether a gestational renal vasodilation occurs in the hypertensive gravida and 2) whether pregnancy exposes the spontaneously hypertensive rat (SHR) kidney to increased glomerular blood pressures and thus ultimately to glomerular injury. These studies demonstrate that there is no gestational vasodilation in the midterm pregnant SHR (renal vascular resistance, 30 +/- 2 vs. 30 +/- 3 (mmHg.ml-1.min in midterm pregnant vs. virgin SHR) and, of importance, no difference in glomerular blood pressure in pregnant vs. virgins (54 +/- 1 vs. 55 +/- 1 mmHg). In the long term after three repetitive pregnancies there is no worsening in glomerular function compared with age-matched virgin SHRs (single nephron glomerular filtration rate, 26 +/- 2 vs. 23 +/- 1 nl/min), perhaps not surprising in view of the lack of change in glomerular hemodynamics during a pregnancy. Additional observations indicated that the midterm pregnant, repetitively pregnant, and virgin SHRs have no vasodilatory response to an intravenous amino acid load. Thus the SHR has no acute renal vasodilatory reserve to a glycine infusion and is also unable to undergo a gestational vasodilation. This has no negative impact on either mother or babies and may actually be beneficial to the long-term health of the maternal kidney. PMID- 2603960 TI - Functional studies in experimental renal cortical necrosis in the rat. AB - Necrosis of the outer two-thirds of the cortex (CN) was induced with boiling water in the left kidney of rats. Two days afterward, morphological damage was shown to be limited to the superficial cortex; deep nephron population was well preserved. Glucose reabsorption under basal and glucose loading conditions, and extraction of p-aminohippurate, used as indices of proximal tubule integrity, were normal in control and experimental kidneys 48 h after cortical necrosis. Basal fractional water and electrolyte excretion did not differ between control and experimental kidneys. Calculated mean single-nephron glomerular filtration rate (GFR) and plasma flow for superficial (SupGFR and SupNPF) and juxtamedullary nephrons (JMGFR and JMPF) were similar to those obtained by micropuncture and Hanssen's technique for SupGFR, and for JMGFR by Hanssen's. Volume expansion led to a 27% increase in calculated SupGFR, but no change in JMGFR. The JMPF increased by 81%, whereas SupNPF increased by only 23%, suggesting that, in this model, GFR of deep nephrons may be independent of plasma flow. The results indicate that deep nephrons retain their functional integrity 48 h after cortical necrosis. After volume expansion fractional excretion of sodium was greater, and fractional water reabsorption less, in CN than in control kidneys. Thus handling of sodium and water by superficial and deep nephrons under basal conditions was similar, but reabsorptive capacity for deep nephrons of CN was lower during volume expansion. The present studies suggest that deep nephrons can maintain relatively normal function in cortical necrosis. PMID- 2603961 TI - Effects of carbonic anhydrase inhibitors on basolateral base transport of rabbit proximal straight tubule. AB - The effect of carbonic anhydrase inhibitors on basolateral base transport was examined in rabbit proximal straight tubules (S2 segment) perfused in vitro by double-barreled pH microelectrodes. Bath HCO3- reduction or Na+ removal induced an initial basolateral voltage (Vbl) depolarization followed by a late-phase depolarization. Administration of 1 mM acetazolamide (ACTZ) to the bath fluid caused a small inhibition of the initial depolarization, and a larger inhibition of the late phase depolarization. Bath HCO3- reduction decreased intracellular pH (pHi), and this pHi decrease was attenuated by ACTZ. Bath Na+ removal also decreased pHi, and this pHi decrease was completely blocked by ACTZ. However, a slow pHi decrease was observed in response to bath Na+ removal when the bath fluid contained ACTZ and the luminal fluid contained 4 mM amiloride. The addition of ACTZ or ethoxyzolamide to the bath caused a rapid Vbl hyperpolarization and pHi increase. These results demonstrate that carbonic anhydrase inhibitors inhibit basolateral Na(HCO3)n transport in intact rabbit proximal tubule cells (S2). The data suggest that at least one of the base species transported by the transporter is HCO3-, and cytosolic carbonic anhydrase is important in converting intracellular OH- to HCO3-. PMID- 2603962 TI - Effects of xanthine oxidase inhibition on ischemic acute renal failure in the rat. AB - To assess the effects of xanthine oxidase (XO) inhibition on ischemic injury, rats were pretreated with oxypurinol (OXY, 5 mg/kg) and subjected to 30 min of bilateral renal artery occlusion. OXY's effect on adenine nucleotide-nucleoside purine base concentrations was determined at 10 and 30 min of ischemia and during reperfusion (5 and 30 min). To assess whether XO-mediated oxidant stress influences the severity of ischemic acute renal failure (IARF), the effects of 1) OXY pretreatment and 2) hypoxanthine infusion were assessed. During ischemia OXY inhibited XO activity (more than fourfold rise in hypoxanthine-xanthine ratios) and induced quantitatively trivial but significant increases in ATP and total adenine nucleotide concentrations (by 30 min). Increased OXY dosage (15 mg/kg) or allopurinol (40 mg/kg) had no greater effects. At 5 min of reflow, OXY maintained XO inhibition but did not influence adenine nucleotide levels. By 30 min of reflow, 17-20% increments in ATP-total adenine nucleotides resulted. Nevertheless, OXY did not lessen the severity of IARF (assessed by azotemia histology at 24 h). Hypoxanthine infusion increased end-ischemic hypoxanthine concentrations by 47%, but it did not change the severity of renal damage. Conclusions include 1) OXY-allopurinol induces intrarenal XO inhibition; 2) XO inhibitors slightly increase late ischemic-reperfusion adenine nucleotide concentrations; and 3) neither XO inhibition nor intrarenal hypoxanthine loading alters the severity of IARF, suggesting that XO-mediated oxidant stress is not a critical, consistent mediator of ischemic renal injury. PMID- 2603963 TI - Experimental Fanconi's syndrome resulting from 4-pentenoate infusion in the dog. AB - Studies were performed in anesthetized dogs to evaluate the effects of 4 pentenoate on urinary electrolyte excretion and renal metabolism. The intravenous administration of 4-pentenoate (1 mumol.kg-1.min-1 during 180 min) markedly increased the urinary excretion of bicarbonate, phosphate, potassium, amino acids, glucose, and various organic anions, whereas that of sodium and chloride also rose but less strikingly. These results suggest that 4-pentenoate markedly inhibits the proximal reabsorption of various solutes and therefore reproduces an experimental Fanconi's syndrome. Despite the rise in renal cortical concentration of alpha-ketoglutarate, glutamine utilization and total ammonia production expressed per 100 ml glomerular filtration rate increased following 4-pentenoate infusion, the ammonia being diverted into the renal vein. This increment in glutamine utilization was equal to the combined rise in the renal production of glutamate and alpha-ketoglutarate. By contrast, renal lactate utilization was drastically reduced. A causal relationship between the decreased renal cortical ATP concentration and the inhibited reabsorption of various solutes is suggested but cannot be established unequivocally. PMID- 2603964 TI - Early adaptation of renal magnesium reabsorption in response to magnesium restriction. AB - Dietary magnesium restriction with hypomagnesia is normally associated with diminished urinary magnesium excretion. Young rats were pair fed control magnesium diets (0.05% MgSO4) and magnesium-restricted diets (less than 0.01% Mg), and tubular magnesium reabsorption was assessed to determine the importance of filtered load (plasma magnesium) and to establish the presence of cellular adaptation of magnesium transport. Urinary magnesium excretion decreased from 17.2 +/- 2.7 to 5.9 +/- 1.2% over 20 h on low-magnesium diets without a change in plasma concentration (0.61 +/- 0.02 mM). This cellular adaptation was rapid (within 5 h), specific (without effect on sodium and calcium), and sensitive (without change in plasma concentration). Micropuncture studies demonstrated that cellular adaptation occurred within the loop of Henle. After 20 h, plasma magnesium fell with an associated further decrease in fractional magnesium excretion. Accordingly, cellular adaptation of magnesium transport occurs with magnesium-deficient diets, and alterations in filtered magnesium and plasma magnesium concentration are not necessary for magnesium conservation. PMID- 2603965 TI - Sodium chloride and water transport in the thin descending limb of Henle of the quail. AB - Birds and mammals can produce hyperosmotic urine, but their renal morphology and urine-concentrating mechanisms differ. To elucidate the countercurrent urine concentration mechanism in birds, we examined the structure and transport properties of the descending limb (DL) of Henle of mammalian-type nephrons in Japanese quail, Coturnix coturnix. In the avian renal medulla, a prominent ring of collecting ducts and scattered thick limbs surrounds a core of capillaries and DLs. Epithelial cells in the upper DL (DLu) have abundant microvilli and shallow, tight junctions; cells in the lower DL are flat and have little interdigitation. Transepithelial voltage was zero when the DLu was perfused and bathed in isosmotic avian Ringer solution. The efflux coefficients (10(-7) cm2/s) for Na (31.7 +/- 2.3) and Cl (24.9 +/- 3.6) were not significantly different and were unaltered by ouabain (10(-4) M) (32.5 +/- 2.2). Diffusional water permeability measured by [3H]H2O was low (73.0 +/- 7.8, 10(-7) cm2/s). Volume flux was nearly zero and increased only slightly when an osmotic gradient was imposed. These results suggest the DLu is highly permeable to Na and Cl and virtually impermeable to water; thus NaCl extruded actively from the thick ascending limb may enter the DL unaccompanied by water. This countercurrent multiplication system by use of single-solute recycling and a transport cascade of graded hairpin turns may help establish an osmotic gradient along the medullary cone. Thus avian and mammalian renal countercurrent multiplication systems may differ. PMID- 2603966 TI - Endocardium modulates myocardial inotropic response to 5-hydroxytryptamine. AB - The endocardium modulates contractile performance of subjacent myocardium in isolated heart muscle. We investigated the effects of 5-hydroxytryptamine (5-HT, 0.01-30 microM) on isolated cat papillary muscles with or without intact endocardium (+E or -E, respectively). Selective endocardial damage by 1-s immersion in 1% Triton X-100 caused reduction in half-isometric relaxation time (RT1/2) and isometric twitch tension (TT), but not maximum unloaded shortening velocity (Vmax). 5-HT caused reduction in RT1/2 in endocardium-intact but an increase in endocardium-damaged preparations (at 30 microM: -12.1 +/- 1.8%, +E; +5.2 +/- 1.5%, -E). Mean percent increases in TT were greater in endocardium damaged muscles (at 30 microM: 37.3 +/- 8.6%, +E; 107.3 +/- 19.5%, -E). In the presence of ketanserin (1 microM), 5-HT reduced RT1/2 in endocardium-intact (at 30 microM: -11.9 +/- 1.3%) but not endocardium-damaged muscles (except slightly at 30 microM) and increased TT at 30 microM by 28.7 +/- 4.9% (+E) and 48.9 +/- 15.6% (-E). In the presence of propranolol (1 microM), 5-HT increased RT1/2 (+E and -E) while increasing TT by 23.3 +/- 7.8% (+E) and 43.5 +/- 2.5% (-E). Endocardium did not influence changes in Vmax. Ketanserin (1 microM), but not propranolol (1 microM), markedly diminished endocardial damage induced by 5-HT (greater than or equal to 10 microM). These results suggest a 5-HT-induced endocardium-mediated "inhibitory" effect (causing earlier isometric relaxation) that is not blocked by ketanserin. PMID- 2603967 TI - Increased myocardial infarct size because of reduced coronary collateral blood flow in beagles. AB - Effects of permanent left circumflex coronary artery occlusion (CAO) were examined in conscious purebred beagles and mongrel dogs, instrumented with miniature left ventricular (LV) pressure gauges, wall thickness gauges in the ischemic zone, catheters in left atrium and aorta, and snares around the left circumflex coronary artery. Blood flow was measured using the radioactive microsphere technique before CAO and at 5 min, 1, 3, and 24 h after CAO. Although CAO reduced myocardial blood flow similarly in beagles and mongrels, significantly less (P less than 0.05) recovery of myocardial blood flow was observed over the following 24-h period in beagles. Infarct size, as determined by triphenyltetrazolium chloride and expressed as percentage of area at risk, was larger (P less than 0.05) in beagles (62.0 +/- 5.1%) than mongrels (42.5 +/- 4.2%). Thus beagles do not tolerate ischemia as well as mongrel dogs and possess fewer functional coronary collaterals resulting in larger infarcts after CAO. PMID- 2603968 TI - Effects of isoflurane and halothane on rapid cooling contractures in myocardial tissue. AB - The effects of isoflurane and halothane on the availability of Ca2+ stored in and released from the sarcoplasmic reticulum (SR) were studied in isolated rabbit papillary muscles by measuring the effects of the anesthetics on rapid cooling contractures, which are known to be activated by Ca2+ released from the SR. Isoflurane (0.3%) reduced the force of the rapid cooling contracture to 57% of control with a marked slowing of the average rate of contracture development and increased the force of the first contraction after rewarming to 133% of control. In contrast, 1.7% halothane, which reduced the rapid cooling contracture to 51% of control (comparable to the value in the presence of 0.3% isoflurane), had little effect on the rate of contracture development and strongly inhibited the first contraction after rewarming to 5% of control. Halothane, but not isoflurane, strongly inhibited postrest potentiated-state contractions, which are also known to be activated by Ca2+ released from the SR. These results suggest that 1) isoflurane inhibits rapid cooling-induced Ca2+ release from the SR without inhibiting Ca2+ release triggered by rapid depolarization as occurs in the potentiated-state contraction, and 2) halothane inhibits contractile activity dependent on Ca2+ released from the SR regardless of mechanism involved. PMID- 2603969 TI - Norepinephrine spillover from skeletal muscle during exercise in humans: role of muscle mass. AB - The purpose of this study was to determine the effect of increasing muscle mass involvement in dynamic exercise on both sympathetic nervous activation and local hemodynamic variables of individual active and inactive skeletal muscle groups. Six male subjects performed 15-min bouts of one-legged knee extension either alone or in combination with the knee extensors of the other leg and/or with the arms. The range of work intensities varied between 24 and 71% (mean) of subjects' maximal aerobic capacity (% VO2max). Leg blood flow, measured in the femoral vein by thermodilution, was determined in both legs. Arterial and venous plasma concentrations of norepinephrine (NE) and epinephrine were analyzed, and the calculated NE spillover was used as an index of sympathetic nervous activity to the limb. NE spillover increased gradually both in the resting, and to a larger extent in the exercising legs, with a steeper rise occurring approximately 70% VO2max. These increases were not associated with any significant changes in leg blood flow or leg vascular conductance at the exercise intensities examined. These results suggest that, as the total active muscle mass increases, the rise in sympathetic nervous activity to skeletal muscle, either resting or working at a constant load, is not associated with any significant neurogenic vasoconstriction and reduction in flow or conductance through the muscle vascular bed, during whole body exercise demanding up to 71% VO2max. PMID- 2603970 TI - Interstitial exclusion of albumin in rat dermis and subcutis in over- and dehydration. AB - We have estimated exclusion of albumin from the interstitial matrix in rats based on measurement of albumin concentration in interstitial fluid, interstitial fluid volume (IFV), and interstitial albumin mass. Measurements were performed separately in dermis and subcutis during control, overhydration (saline infusion corresponding to 10% of body weight), and dehydration. Exclusion during control was 1.03 (SD = 0.47; n = 7 rats) and 0.85 (SD = 0.21; n = 7 rats) ml/g fat-free dry wt in subcutis and dermis, respectively. This corresponded to 44.1 and 57.8% of IFV, respectively. Collagen and hyaluronan were responsible for two-thirds and one-third of the exclusion, respectively. During overhydration the increase in albumin available volume was 70% of the increase in IFV. Both the collagen and the hyaluronan excluded compartment of the excluded volume changed when altering IFV. These data suggest that the colloid osmotic pressure in the albumin available compartment can change the volume of both the collagen and hyaluronan compartments of the excluded volume. The following changes in composition of the interstitial matrix were observed: albumin mass in subcutis decreased by 20% during dehydration and increased by 30% during overhydration, and overhydration reduced hyaluronan content by 20% in subcutis. PMID- 2603971 TI - Mechanical and electrical properties of cardiomyopathic hearts of Syrian hamsters. AB - To determine whether the cardiomyopathy that develops in the Syrian hamster before the occurrence of congestive heart failure is associated with mechanical and electrical alterations consistent with myocardial dysfunction, left ventricular posterior papillary muscles of control and cardiomyopathic animals at 120 days of age were studied in vitro. Moreover, the electrocardiographic response to ouabain was investigated in vivo to analyze the arrhythmogenic potential of the cardiomyopathic heart to glycoside exposure. Results showed a decreased tension-generating ability of the myocardium in the diseased animals, which was accompanied by a prolongation of the timing parameters of contraction and an increase in the duration of the repolarization phase of the transmembrane action potential. Furthermore, the velocity of isotonic muscle shortening and relengthening was depressed at all physiological loads. Glycoside infusion elicited premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation in diseased hamsters much earlier in time than in healthy controls. The impairment in mechanical performance in association with the abnormality in membrane electrical activity may be responsible for the progression of the disease process and the occurrence of lethal arrhythmias in this animal model. PMID- 2603972 TI - Modulation of effect of extracellular calcium buffering in cardiac muscle. AB - The buffering of extracellular calcium by citrate, with identical free calcium levels in the buffered and unbuffered medium, was previously found to markedly reduce tension in frog and guinea pig atria. We now report the following results. 1) In guinea pig, postest contractions are not reduced by citrate. 2) In frog the negative inotropic effect of citrate is greatly attenuated by partially replacing extracellular sodium concentration ([Na+]o) with lithium or sucrose. In contrast, in low [Na+]o, sodium salts of weak acids (which cause intracellular acidosis) still reduce tension. These findings strongly support the suggestion that citrate does not reduce tension directly, e.g., by causing intracellular acidosis or by reducing voltage-dependent calcium currents. 3) Higher stimulation rates also decrease the effect of citrate. 4) Treatment with neuraminidase or phospholipase D, both of which alter sarcolemmal calcium binding, dose not change the effect of citrate. 5) The positive inotropic effect of strophanthidin is reversibly lost in the presence of citrate. Our results provide a different, novel approach to support earlier suggestions that the extracellular matrix and/or the sarcolemma contain abundant calcium-binding sites that supply some of the calcium for contraction. Citrate presumably binds calcium more strongly, thereby "trapping" calcium released from the extracellular "stores," so that less calcium is made available for contraction. The inotropic effect of cardiac glycosides may also depend on the calcium that is bound to these stores. PMID- 2603973 TI - Effects of left ventricular pressure reductions on right ventricular systolic performance. AB - Reductions in left ventricular pressure (LVP) have been shown to produce a leftward shift of the interventricular septum and to reduce left ventricular contribution to right ventricular performance. To evaluate the magnitude of this contribution in the intact heart, five anesthetized pigs were implanted with a left prosthetic ventricle to gradually decrease LVP while maintaining arterial systemic pressure. Three descriptors of RV global and regional systolic function were studied in the septum to free wall (RVSFW) and anterior to posterior (RVAP) dimensions and in an outflow tract segment length (RVSL), during both steady state and transient inferior vena cava occlusion. LVP gradual reduction from 102 +/- 4 to 11 +/- 3 mmHg (90% decrease in peak systolic pressure) produced no changes in the RV global stroke work curve or in the RVAP and RVSL pressure dimension relationships. However, the reduction in LVP resulted in parallel shifts in the RVSFW dimension, with 16.6 +/- 6.7% increase in the intercept D(o) of the end-systolic relationship and 16.5 +/- 2.5% increase in D(o) of the dimensional stroke work relationship, with no significant changes in their respective slopes as calculated by linear regression. Therefore, in the normal intact heart, large reductions in left ventricular pressure affect the geometry of the right ventricle because of septal shifting, but there is a negligible net effect of this anatomic ventricular interaction on overall right ventricular performance. PMID- 2603974 TI - Autonomic response to coronary occlusion in animals susceptible to ventricular fibrillation. AB - Disturbances in autonomic control during myocardial ischemia may contribute significantly to the development of malignant cardiac arrhythmias. Therefore acute ischemia was induced in 29 mongrel dogs with healed myocardial infarctions during an exercise test. Seventeen animals developed ventricular fibrillation (susceptible, S), whereas 12 dogs did not (resistant, R). Before the exercise plus ischemia test a coronary occlusion was made at rest. The amplitude of respiratory sinus arrhythmia (0.24- to 1.04-Hz component of R-R interval fluctuation) was used as an index of cardiac vagal tone. Acute ischemia elicited a significantly larger heart rate increase in susceptible animals (S: control 115.6 +/- 0.8, occlusion 176.4 +/- 8.2 beats/min vs. R: control 114.6 +/- 8.9, occlusion 145.7 +/- 7.5 beats/min). Accompanying the heart rate increase were significantly greater reductions in the cardiac vagal tone index in the susceptible animals. (S: control 6.4 +/- 0.3, occlusion 2.2 +/- 0.6 ln ms2 vs. R: control 6.6 +/- 0.4, occlusion 5.1 +/- 0.5 ln ms2). beta-Adrenergic receptor blockade reduced the heart rate increases but exacerbated the reductions in the cardiac vagal tone index. These data suggest that coronary artery occlusion elicits a significantly greater increase in sympathetic activity coupled with a greater reduction in parasympathetic activity in animals subsequently shown to be susceptible to ventricular fibrillation. PMID- 2603975 TI - Effects of a stabilized endothelium-derived relaxing factor on the coronary vasculature in awake dogs. AB - The effects of a partially purified endothelium-derived relaxing factor (EDRF) stabilized by acidification from cultured bovine aortic endothelial cells stimulated with the calcium ionophore A23187 on coronary and peripheral vasculature were examined in five awake dogs. The dogs were chronically instrumented with miniature arterial dimension crystals and Doppler flow probes. Intracoronary or intra-arterial infusions of this EDRF induced a rapid (less than 15 s) significant increase in the proximal vessel diameter (P less than 0.02). The duration of proximal dilation response to this EDRF persisted up to 6 min, whereas the smaller changes in distal flow were more transient (less than 1 min). Similar but more pronounced changes in the proximal arterial dilation and distal flow occurred with infusion of nitroglycerin (0.4 mg). No vasoactive changes were observed during infusions of the control vehicle. The vasodilatory effects to this EDRF occurred in the absence of changes in aortic and left ventricular pressure, rate of pressure development (dP/dt), and heart rate. These data demonstrate that infusion of this partially purified relaxing factor from cultured endothelial cells causes vasodilation in vivo with a vasoactive profile similar to nitroglycerin. The biological effects of this EDRF persist significantly longer than the extreme lability of EDRF at neutral pH (approximately 6 s), consistent with its in vitro effects. Despite the demonstration of rapid inactivation of EDRF in vitro by hemoglobin, high oxygen tension, and plasma, the study shows that this EDRF can have significant in vivo vasoactive effects. PMID- 2603976 TI - Adrenergic regulation of calcium-deficient hypertension in chick embryos. AB - Chick embryos rendered calcium deficient by long-term culture outside the eggshell develop hypertension and tachycardia (R. Tuan and H. Q. Nguyen, J. Exp. Med. 165: 1418-1423, 1987). To characterize the hypertension of cultured shell less (SL) chick embryo, we have compared their cardiovascular response to adrenergic drugs with normal (NL) embryos at day 14 of incubation. Blood pressure and pulse rate were measured before and after administration of norepinephrine (NE), phentolamine (PA), isoproterenol (IP), and propranolol (PP). Base-line blood pressures (systolic and diastolic) were uniformly higher in SL than NL embryos. In both embryos, blood pressure was elevated by NE and PP but lowered by IP and PA; pulse rates were decreased by PP and PA and increased by NE and IP. Pharmacological sensitivity to NE and PA, based on their effective dosages and magnitude of response in blood pressure and pulse rate, was higher in SL embryos. On the other hand, the embryos did not differ significantly in their sensitivity to IP and PP. The plasma concentration of catecholamines was considerably higher in SL embryos. Although serum calcium was lower in SL embryos, myocardial calcium content was not significantly different. Thus the cardiovascular function of SL embryos is likely to be under more sensitive and potentiated alpha-adrenergic regulation, perhaps a result of different calcium handling by several tissues (e.g., myocardium). These properties of the SL chick embryo indicate that it is a novel and useful experimental system to study the relationship between calcium homeostasis and development of hypertension. PMID- 2603977 TI - Nonuniformity and volume loading independently influence isovolumic relaxation rates. AB - We examined the influence of loading conditions and nonuniformity of left ventricular (LV) function on the rate of LV pressure fall in seven anesthetized dogs. Loading conditions were altered with vena cavae occlusions and/or intravenous infusions of dextran. Nonuniformity was produced by injecting 8-20 ng of isoproterenol into the mild left anterior descending coronary artery to produce an asynchronous and early onset of segment lengthening in the anterior wall. Temporal and regional nonuniformity were quantified with indexes derived by comparing segment lengths in the anterior and posterior walls, measured with midwall sonomicrometers. The rate of LV pressure fall was assessed with peak dP/dt, the time constant, tau, and the duration of isovolumic relaxation. Volume loading decreased the rate of LV pressure fall without altering the nonuniformity indexes. Intracoronary isoproterenol produced nonuniformity and decreased the rate of LV pressure fall without altering global loading conditions. The effects of isoproterenol (in a constant dose) were similar irrespective of the LV volume. We conclude that in the intact, ejecting left ventricle, loading conditions and nonuniformity are important determinants of the rate of LV pressure fall, but these two factors exert their influence by mechanisms that are largely independent. PMID- 2603978 TI - Contractility is the main determinant of coronary systolic flow impediment. AB - We measured the relation between coronary flow amplitude (delta F = Fd-Fs; where d is diastolic and s is systolic) and developed left ventricular pressure (delta PLV = Ps-Pd) at a constant perfusion pressure of 75 mmHg (10 kPa) in the maximally vasodilated blood-perfused isolated cat heart for different steady state levels of contractility (protocol A) and during transients in contractility (protocol B). Contractility was defined as the slope of the end-systolic pressure volume relation (Emax). From protocol A it appeared that the coronary flow amplitude was only weakly related to left ventricular pressure at each steady state level of contractility studied. However, the coronary flow amplitude was strongly related to the different levels of contractility. In protocol B, contractility was changed over a wide range of values (0-100%) but developed pressure and contractility changed simultaneously. Using multiple linear regression analysis, we found that contractility has approximately 10 times (range: 2.8-57.3) stronger effect than left ventricular pressure on coronary flow amplitude (n = 10 experiments). These data and our earlier observations suggest that it is the difference in stiffness of cardiac muscle between systole and diastole that determines coronary flow amplitude. PMID- 2603980 TI - Dilator response of rat mesenteric arcading arterioles to increased blood flow velocity. AB - Arcading arterioles (average diam 68 microns ID) connecting adjacent triangular vascular sectors in the rat mesentery were examined in vivo for the presence of flow-dependent vasodilation. When a feed artery to one of these sectors was occluded, the affected sector was supplied by collateral flow through the arcading arteriole, and red cell velocity in the arteriole increased by 10-66 mm/s. The velocity increase was followed (with an average delay of 7.7 s) by dilation of the arcading arteriole, which averaged 68%. The dilation was closely correlated with red cell velocity (r = 0.96), volume flow (r = 0.96), and wall shear rate (r = 0.89). The dilation was sustained for the duration of increased velocity (1-10 min) and was not affected when direction of flow in the arteriole was reversed. The flow-induced dilation was equal to the maximal dilation attained with topically applied papaverine. Dilation of the arcading arteriole could be almost completely abolished if the arteriole was also occluded during occlusion of a feed artery. These observations indicate that a potent flow dependent dilator mechanism is present in arcading arterioles of rat mesentery and may play an important role in local regulation. PMID- 2603979 TI - Dihydroxyphenylglycol as an index of neuronal uptake in dog saphenous vein. AB - Dihydroxyphenylglycol (DOPEG), the metabolite of norepinephrine (NE) that arises intraneuronally, was measured together with NE in superfusates collected before, during, and after nerve stimulation and in extracts of dog saphenous vein after superfusion and electrical stimulation (ES). Different concentrations of NE in the synaptic clefts were achieved by treating tissues with corticosterone, corticosterone and yohimbine, corticosterone and cocaine, or by omitting drugs from the superfusate. NE and DOPEG were quantitated by liquid chromatography with electrochemical detection. The time courses of NE overflow and DOPEG efflux into superfusate were followed. The amounts of DOPEG in superfusates under basal conditions were two to four times higher than the amounts of NE and progressively increased during ES except in tissues with neuronal uptake inhibited. NE overflow reached a steady state within the first 6 min of ES. Increased NE concentrations in synaptic clefts resulted in increased DOPEG production except where neuronal uptake was inhibited. The increased DOPEG production during ES appears to reflect the increased rate of neuronal uptake, which results in more NE being available for intraneuronal metabolism. No evidence was found that newly formed DOPEG was delayed in leaving the tissue. Thus the increase in DOPEG production that occurs during ES may be useful as an index of neuronal uptake of NE in dog saphenous vein. PMID- 2603981 TI - Effect of arteriovenous fistula size on arterialized and host livers in rats. AB - In studying the hemodynamic relationship and behavior of peak blood flow indexes at different sizes of arteriovenous fistulas (AVF) using arterialized partial liver transplants (PLT), 96 male Wistar rats served as donors and recipients of heterotopic PLT in an acute phase study using ether anesthesia. AVF of 1, 2, and 3 mm were compared with a control group (0 mm) along the "index of peak perfusion rate" of blood flow, the dependent variable. We found that with increasing AVF sizes, a progressive fall in the peak blood flow in the host livers (P less than 0.01, r = -0.51) and a similar rise in the same index in the graft livers (P less than 0.01, r = +0.76) were documented. Also noted was a gradual fall in the cardiac pulsatility component of perfusion to both host and graft livers at AVF sizes of 2 and 3 mm. The same component of perfusion to host and graft livers was best at AVF size of 1 mm. It was concluded that a 1-mm AVF provided the best degree of arterialization to a PLT. PMID- 2603982 TI - Ventricular remodeling induced by acute nonocclusive constriction of coronary artery in rats. AB - To determine the consequence of acute nonocclusive constriction of the epicardial coronary artery on the adaptation of the left ventricle and its impact as a function of age, the left main coronary artery was narrowed in rats 4 and 12 mo of age, and the animals were killed 45 min later. Similar reductions in the luminal diameter, averaging 4%, were obtained in both groups of animals, and this change resulted in an increase in left ventricular end-diastolic pressure and a decrease in positive and negative change in pressure overtime (dP/dt) and in peak developed ventricular pressure. Left ventricular volume increased by 66% and 56% at 4 and 12 mo because of increases in both the longitudinal and transverse chamber diameters. In contrast, wall thickness decreased by 27% and 35%, whereas sarcomere length increased only by 8.0% and 6.0%, respectively. These changes implied the occurrence of side-to-side slippage of myocytes within the wall to accommodate the larger chamber volume. The alterations in myocardial performance combined with the variations in ventricular size and wall thickness produced a marked elevation in diastolic and systolic wall stress. Moreover, myocyte cell damage in the form of contraction bands and disorganization of the intercalated disc region was seen. No consistent difference was found in any of the parameters measured as a function of age. Measurements of resting coronary blood flow across the left ventricular wall before coronary artery narrowing were comparable with those obtained 45 min after constriction. In conclusion, acute nonocclusive coronary artery stenosis has profound detrimental effects on the function and structure of the myocardium in the absence of an impairment of resting coronary blood flow. PMID- 2603983 TI - Posterior hypothalamic influences on cardiovascular effects of aortic nerve stimulation. AB - The purpose of this study was to examine the influence of stimulation of the posterior hypothalamus on the baroreflex responses produced by stimulation of the aortic depressor nerve. Animals were initially anesthetized and implanted with a bipolar electrode in the posterior hypothalamus. Three to 5 days later, animals were anesthetized with urethan, and the left aortic depressor nerve was dissected and placed on a bipolar platinum-iridium electrode. The effects of electrical stimulation of the posterior hypothalamus (0, 160, and 280 microA) were examined in baroreflex-intact and acutely sinoaortic baroreceptor-denervated animals, and the responses to aortic nerve stimulation (2, 8, 16, and 32 Hz) were examined during each level of hypothalamic stimulation. The first set of experiments was performed in baroreceptor-intact animals; e.g., in animals with arterial baroreceptor inputs intact from both carotid sinus regions in addition to intact right aortic baroreceptor afferent pathways. In that group, stimulation of the posterior hypothalamus attenuated the bradycardia and depressor effects of aortic nerve stimulation. When influences from other baroreceptor inputs were removed with acute sinoaortic baroreceptor denervation, posterior hypothalamic stimulation interrupted the reflex bradycardia due to aortic nerve stimulation; however, the depressor response to aortic nerve stimulation was not attenuated. Similar to the arterial pressure response, hypothalamic stimulation did not attenuate the decreases in mesenteric and iliac vascular resistance produced by aortic nerve stimulation in the baroreflex-denervated group. We conclude that posterior hypothalamic stimulation attenuates baroreflex-mediated bradycardia but does not alter baroreflex control of arterial pressure and peripheral vascular resistance. PMID- 2603984 TI - Role of calcium in U 46619 and PGF2 alpha pulmonary vasoconstriction in rat lungs. AB - The role of calcium and calmodulin during U 46619 and PGF2 alpha-induced pulmonary vasoconstriction was studied in isolated rat lungs perfused with Krebs Ringer bicarbonate (KRB) or calcium-free KRB. In lungs perfused with KRB, bolus injections of U 46619 (0.2 microgram) and PGF2 alpha (40.0 micrograms) resulted in a 48.0 +/- 4.0 and 23.9 +/- 2.5% increase in mean pulmonary artery pressure, respectively. During lung perfusion with KRB without calcium, the U 46619 response decreased to 31.1 +/- 7.5% whereas the PGF2 alpha response increased to 34.6 +/- 4.1%. Repeated challenges with PGF2 alpha in the KRB without calcium resulted in reduction of the response to 11.8 +/- 1.2%; the U 46619 response was unaltered. The intracellular calcium blocker, 8-(N,N-diethylamino)-octyl-3,4,5, trimethoxybenzoate HCL (TMB-8) significantly attenuated the pressor response to U 46619 at low doses and PGF2 alpha at high doses. The calmodulin inhibitor trifluoperazine (TFP 100 microM) attenuated the vasoconstrictor response to U 46619 by 54%, whereas the PGF2 alpha was unchanged. However, in the calcium-free KRB, TFP attenuated the pressor response to both U 46619 and PGF2 alpha. The U 46619 pressor response depends on intracellular and extracellular calcium to achieve calmodulin-dependent vasoconstriction. PGF2 alpha requires extracellular calcium to replenish depletable intracellular calcium pools and is independent of calmodulin activation. PMID- 2603985 TI - Reflex stimulation of sympathetic outflow during rhythmic exercise in humans. AB - The aim of this study was to determine whether a chemically generated reflex arising in nonischemic skeletal muscle normally increases sympathetic outflow during rhythmic exercise. To accomplish this aim, we recorded muscle sympathetic nerve activity (MSNA, peroneal nerve) in conscious humans during exercise interventions designed to alter the relationship between muscle blood flow and metabolic demand. Under normal conditions, MSNA increased during moderate but not during mild levels of rhythmic handgrip (0.67 Hz) and one-arm cycling (0.83 Hz). MSNA remained elevated when the moderate level of rhythmic handgrip was followed by forearm vascular occlusion, a maneuver that sustains muscle chemoreflex stimulation. Complete arm vascular occlusion was needed to increase MSNA during mild arm cycling, whereas even partial vascular occlusion greatly amplified the stimulation of MSNA normally produced by the moderate level of arm cycling. We conclude that a chemically generated reflex arising in nonischemic working muscle plays an important role in the normal activation of sympathetic discharge to nonexercising leg muscles during moderate but not during mild levels of rhythmic arm exercise. PMID- 2603986 TI - Effects of elevated venous pressure on capillary permeability in cat hindlimbs. AB - We investigated the effects of elevated venous pressure, Pv, (up to 140 mmHg) on the solvent drag reflection coefficient, sigma f, for protein and on the capillary filtration coefficient, CFC, in the isolated cat hindlimb perfused at constant flow. The perfusate contained 30% cat plasma and the remainder was a dialyzed albumin-electrolyte mixture. Cat red cells were added to a hematocrit of approximately 2%. sigma f was measured from the changes in hematocrit and plasma protein concentration (Integral-Mass Balance method) resulting from the fluid filtration caused by the Pv elevation. CFC was measured from the slope of the limb weight recording 2-4 min after the Pv elevation. sigma f decreased linearly from 0.807 (Pv less than 50 mmHg) to approximately 0.2 at 140 mmHg. CFC increased linearly from 0.0086 ml.min-1.mmHg-1.100 g-1 to about 0.04 over the same pressure range. A weight-independent filtration coefficient calculated from the change in hematocrit and a measurement of the initial perfusate volume gave comparable results, except at the very highest of pressures, where this coefficient was sometimes 20-40% less than CFC. Successive sigma f determinations at Pv at about 40 mmHg did not return to control after an initial measurement in which Pv was approximately 110 mmHg. Pore-theory analysis of the data suggests that the elevated Pv causes large pores to open as opposed to the stretching of small pores. Also, these large pores may remain open for a period of hours. PMID- 2603987 TI - Analysis of the interval-force relationship in rat and canine ventricular myocardium. AB - The mechanism of the negative force staircase in thin rat ventricular trabeculae was investigated and compared with the positive force staircase in dog ventricular muscles of comparable diameter. Increasing stimulus frequency from 0.2 to 0.5 and 1 Hz resulted in a stepwise reduction of twitch amplitude that was demonstrated in both 1.25 and 2.5 mM external calcium concentration ([Ca]o). The negative staircase was associated with no change in the amplitude of postrest contraction or rapid-cooling contracture at either [Ca]o investigated. Hence, neither decreased loading nor overloading of the rat sarcoplasmic reticulum with calcium during the steady state can be invoked as a likely explanation for the negative staircase. The results are consistent with a frequency-dependent increase in the refractoriness of the sarcoplasmic reticular calcium release process or a decrease in the amount of trigger for calcium release, assuming that the amount of calcium present in the release pool is constant from one frequency to the next. In contrast to the rat, canine ventricular muscle exhibited a positive force staircase, the slope of which depended on [Ca]o, as well as a frequency-dependent increase in postrest contraction and rapid-cooling contracture. Data obtained from this series of experiments suggests that increased filling of the release pool within the sarcoplasmic reticulum with calcium underlies the inotropic effect of high-frequency stimulation in canine ventricular muscle. PMID- 2603988 TI - Cardiovascular control by arterial and cardiopulmonary baroreceptors in awake dogs with atrioventricular block. AB - We studied reflex responses to pressure changes at arterial and cardiopulmonary baroreceptors in five awake dogs with atrioventricular block before and after baroreceptor denervation. We changed ventricular pacing rate and blood volume to vary cardiac output and arterial (MAP) and central venous pressure (CVP). We determined peripheral resistance (TPR) and atrial rate (HRA) as responses. In the intact animal, regression analysis showed an average relationship across dogs of TPR = 169-0.69 MAP-1.952 CVP + error. Correlation (r) between observed and predicted TPR was 0.83. For HRA, regression indicated HRA = 291.66-2.319 MAP + 8.144 CVP + error (r = 0.899). TPR and MAP are percent of control at 90 beats/min; CVP is in mmHg; HRA, in beats/min. Although its coefficient is smaller, MAP explains approximately 69% of the variation in TPR. After arterial baroreceptor denervation, effects of MAP on TPR were insignificant and the coefficient for CVP increased. Subsequent vagal block eliminated all reflex responses. Effects from the two receptor sites sum linearly. They act cooperatively with changes in blood volume, but oppose one another with cardiac output changes. PMID- 2603989 TI - Characterization of intact mesenteric lymphatic pump and its responsiveness to acute edemagenic stress. AB - The contractile properties of the mesenteric collecting lymphatics of the rat were analyzed under control conditions and during periods of enhanced lymph formation using in vivo microscopic techniques. Pressure and diameter were simultaneously monitored in microscopic collecting lymphatics, and lymphatic pump function was analyzed in accordance with basic principles of cardiac mechanics. The lymphatic contractile cycle was divided into two phases of systole and four phases of diastole. Under control conditions, lymphatics contracted with a frequency of 6.4 +/- 0.61 beats/min and ejected approximately 67% of their end diastolic volume. Ten minutes after the rate of lymph formation was elevated by plasma dilution, end-diastolic diameter, contraction frequency, ejection fraction, and stroke volume increased. Pressure in the lymphatic network became less pulsatile in high lymph flow states. Contractility, an index of inotropic changes in lymphatic pump, was unaltered when lymph flow was increased by plasma dilution. Furthermore, the maximal shortening velocity of lymphatic smooth muscle did not change during periods of enhanced lymph flow. Thus it appears that passive increases in the rate of lymph formation exert few, if any, inotropic effects on the lymphatic pump. The augmented stroke volume and contraction frequency appear to result mainly from intrinsic stretch-dependent mechanisms set in motion by elevated preload. These data represent the first comprehensive characterization of both the flow-generating and muscle characteristics of intact collecting lymphatics and provide a basis for future studies on the physiological regulation of lymphatic contraction. PMID- 2603990 TI - Evaluation of systolic effectiveness and its determinants: pressure/midwall volume relations. AB - It is generally agreed that systolic performance of a heart chamber is the fractional inward displacement of its wall during contraction and that this depends on preload, afterload, and characteristics of the relation between afterload and end-ejection dimensions. However, there is no consensus on the details of this statement. How can one define and identify the wall element, the displacement of which best expresses performance? What is preload? What parameters best characterize the relation between afterload and end-ejection dimensions? Dividing a thick-wall compliance equation by a thick-wall pressure equation reveals the midwall element, the normalized displacements of which depend consistently on normalized pressure changes according to wall properties regardless of wall-to-cavity ratio. This midwall element's reference dimensions best express chamber size, its reference-normalized dimensions best express wall stretch or distension, and its fractional displacements best express systolic performance. The hydraulically unloaded state is a poor reference for expressing size, normalizing dimensions, and defining chamber characteristics; it is inaccessible, immeasurable, acutely variable, and not a mechanically unloaded state. Therefore stiffness is neither a characteristic nor an expression of systolic vigor. A better reference state is the "average basal end-diastolic distension to which the chamber is accustomed"; it is accessible, measurable, and a state where stretches throughout the wall are near a characteristic value. End diastolic midwall dimension relative to its average basal value is a valid expression of preload. There are two main hydrodynamic characteristics expressing systolic vigor: 1) peak isovolumic pressure at reference distension and 2) displacement from reference distension if afterload were zero. An additional characteristic is shape of the pressure-volume relation. It appears possible to account for systolic performance in terms of preload, afterload, and these hydrodynamic characteristics. PMID- 2603991 TI - Microvascular exchange and interstitial volume regulation in the rat: implications of the model. AB - The present work uses and extends a dynamic mathematical model [J. L. Bert, B. D. Bowen, and R. K. Reed. Am. J. Physiol. 254 (Heart Circ. Physiol. 23): H384-H399, 1988] to investigate microvascular exchange and interstitial fluid volume regulation in the rat. Alternative concepts of transcapillary exchange as well as other parametric changes were incorporated into the model. In all cases, predictions resulting from these changes did not describe the available experimental information as well as the original model. A sensitivity analysis of the model showed the microvascular exchange system to be well regulated near its normal steady-state conditions through passive readjustment of the forces participating in the volume regulation. The transient rates of fluid and protein exchange were studied in order to determine the mechanisms inherent in the model that lead to fluid volume regulation during episodes of increased venous pressure and hypoproteinemia. In addition to interstitial compliance, lymph flow characteristics, and washdown of interstitial proteins, it was found that the magnitude and direction of reabsorption played an important role in the regulation process. Edema was always associated with a permanent reversal of the reabsorptive flow. PMID- 2603992 TI - Heart rate spectral analysis of fasting-induced bradycardia of cattle. AB - The autonomic mechanisms of fasting-induced bradycardia of cattle were studied using heart rate spectral analysis. This was performed on digitized, lead II, surface electrocardiograms from conscious, fed, and 48-h-fasted adult cows. Fasting resulted in a significant (P less than 0.05) decrease in resting heart rate and a significant (P = 0.0041) increase in low frequency (0-90 mHz) power spectral area. Administration of atropine sulfate (0.02 mg/kg iv) in either the fed or fasted state resulted in a significant (P less than 0.001) decrease in both low-frequency and high-frequency (100-400 mHz) power spectral areas. Significant (P less than 0.05) increases in serum total bilirubin, inorganic phosphorus, and total protein were associated with fasting. Significant decreases were seen in fasting serum aspartate aminotransferase and potassium values. Manual evacuation of the rumen of seven steers with chronic rumen fistulae resulted in a mean percent decrease in heart rate of 22 +/- 0.9% (mean +/- SE). These results indicate that in normal cattle a decrease in ruminorecticular fill results in a reflex slowing of the heart rate, due predominantly to an increase in parasympathetic tone. PMID- 2603993 TI - Response of rainbow trout to constant-pressure and constant-volume hemorrhage. AB - Plasma oncotic pressure (OC), protein concentration (P), osmolality (Osm), and hematocrit (Hct) were measured in conscious rainbow trout subjected to 120 min of constant-pressure (CPH) or constant-volume (CVH) hemorrhage. Blood volume, tissue red cell, and plasma space were determined in control and CPH trout with 51Cr labeled red cells and 125I-albumin. At the onset of CPH, blood loss exceeded 1.5 ml.min-1.kg-1 but quickly dropped to a constant rate of 0.1 ml.min-1.kg-1 by 15 min. After 2 h, 73% of the initial blood volume was lost, and Hct, OC, and P were reduced by 55 +/- 3, 39 +/- 4, and 19 +/- 9%, respectively; Osm did not change. Calculated blood volume was reduced by 39% (51Cr method) or by 56% (125I method). Red cell space was reduced in all tissues except brain. Plasma space decreased in stomach, increased in liver and kidney, and was unchanged in other tissues. CVH had similar effects on Hct, OC, and P, while Osm and plasma sodium increased. The time required for arterial pressure to recover to within 90% of control increased with successive bleeding from 39 to greater than 160 min. Twenty-four hours after CVH, Hct remained depressed, while all other parameters were returning toward control levels. Trout incorporate a variety of mechanisms to respond to hemorrhage, including mobilization of stored blood and reabsorption of fluid from interstitial and probably intracellular sources. High permeability of trout capillaries to protein may facilitate the restoration of protein and fluid and allow fish to survive extensive hypovolemia. PMID- 2603994 TI - Anorexic effects of interleukin 1 in the rat. AB - Interleukin 1 (IL-1) administration produces anorexia. Among unanswered questions about this effect are 1) whether it plays a role in the cachexia associated with chronic infection and cancer, and 2) whether IL-1 acts directly on food intake or indirectly by first lowering the set point for body weight. To investigate these questions, rats were infused with recombinant IL-1 continuously for 14 days through osmotic minipumps. Tolerance to the anorexic effects of the infusion developed within a few days. Control experiments showed that neither loss of IL-1 potency nor failure in the delivery system were responsible for recovery of food intake. Prior weight reduction completely overrode the anorexic effects of IL-1; previously food-restricted rats were hyperphagic initially despite receiving IL 1. This result is consistent with the view that IL-1 lowers the set point for body weight, but the development of tolerance prevented the full evaluation of this interpretation. PMID- 2603995 TI - Ambient temperature and food costs: effects on behavior patterns in rats. AB - Eating, drinking, wheel running, and nesting were recorded continuously in animals living in cages where they foraged for and consumed food by completing operant bar-press requirements. The ambient temperature was either 24 or 0 degrees C. Two food costs, that of initiating meals and that of pellets within meals, were separately manipulated at each temperature. Compared with room temperature, the cold temperature produced a doubling of food and water intake and a greater than twofold increase in nesting time each day. Running behavior was not altered. Regardless of temperature, the cost of initiating meals influenced the frequency and size of meals but did not affect total food intake or time spent feeding, and this cost had no effect on any other activity. As the cost of pellets within meals increased, the time spent feeding increased and there was a decline in daily food intake. The change in intake was greater at the cold temperature because in the cold the rats did not increase daily feeding time sufficiently to maintain intake as pellet cost increased. Such an increase in feeding time would have required that less time be spent in one of the other activities. PMID- 2603996 TI - In vitro reactivity of dog cavernous carotid artery to stretch and adrenergic stimulation. AB - The reactivity of the dog cavernous carotid artery to stretch, field electrical stimulation, and norepinephrine was studied using arterial segments under isometric conditions. Light microscopy revealed that this artery is of muscular type and its external surface is covered by venous endothelium, and fluorescence microscopy showed a dense adrenergic innervation. On stretch, arteries exhibited an immediate, transient contraction (phasic response) and a late, maintained contraction (tonic response) that were unaffected by tetrodotoxin (10(-6) M) or endothelium removal but were reduced by the inhibitors of cyclooxygenase indomethacin (10(-6) M), acetylsalicylic acid (3 x 10(-5) M), or meclofenamate (10(-5) M). Electrical stimulation (0.5-4 Hz) contracted the arteries in a frequency-dependent manner, and the response was reduced by tetrodotoxin, phentolamine, (10(-6) M), or the inhibitors of cyclooxygenase used but was unaffected by endothelium removal. Norepinephrine (10(-9)-3 x 10(-4) M) caused dose-dependent contraction that was blocked by phentolamine and by the inhibitors of cyclooxygenase but was not modified by endothelium removal. The results indicate that the dog cavernous carotid artery develops myogenic tone on stretch and contracts on adrenergic stimulation. They also suggest that in these responses prostaglandins but not the endothelium are involved. Therefore, the cavernous carotid artery, because of its location and reactivity, could be of relevance in regulating blood flow or pressure within the cerebral circulation when arterial pressure or adrenergic activity increases. PMID- 2603997 TI - Effects of prolonged exercise on puberty and luteinizing hormone secretion in female rats. AB - Immature female rats were required to run for prolonged periods of time to obtain food. The amount of food they earned was adequate for full pubertal development and moderate growth under nonworking conditions, but both processes were blocked by the exercise requirement. Prolonged exercise also blocked the pulsatile release of luteinizing hormone (LH); only two LH pulses were seen in seven exercising females during a total of 24 h of monitoring at 8 wk of age. By comparison, almost 1 pulse/h was seen in postpubertal, normally growing females of this same age during metestrus. When the exercising females' running requirement was relaxed at 8 wk of age they experienced rapid catch-up growth and reproductive development. Both basal secretion and LH pulse frequency increased markedly within 48 h, and most of these females ovulated during the third dark period after relaxation. Altogether, the experimental paradigm and techniques employed here yield highly predictable results, and they should prove useful for exploring other neuroendocrine pathways through which excessive exercise antagonizes reproduction. PMID- 2603998 TI - Effects of 2-deoxy-D-glucose on sympathetic nerve activity to interscapular brown adipose tissue. AB - The effects on firing rate of sympathetic nerves to interscapular brown adipose tissue were measured after induction of intracellular glycopenia by peripheral or central administration of 2-deoxy-D-glucose (2-DG). Injection of 2-DG (250 mg/kg body wt) into the jugular vein rapidly suppressed the sympathetic activity, which declined 84% within 10 min after the injection. This suppression persisted for at least 40 min. Hyperglycemia did not affect the sympathetic activity but partially inhibited the suppressive effect of 2-DG injection. Acute vagotomy failed to block the suppressive effect of 2-DG. Injection of 2-DG (2.5 mg/rat) into the third cerebral ventricle suppressed the sympathetic activity. This suppression was followed by gradual recovery. Saline injection did not affect the sympathetic activity. We conclude that cellular glycopenia induced by injecting 2-DG peripherally or into the third cerebral ventricle suppresses the sympathetic activity to brown adipose tissue. The results are consistent with the hypothesis that an acute energy shortage decreases the thermogenesis in interscapular brown adipose tissue by suppressing sympathetic neural activation of this tissue. PMID- 2603999 TI - Lateral hypothalamic injection of 2-deoxy-D-glucose suppresses sympathetic activity. AB - To investigate the effects of glucoprivation on sympathetic nerve activity to interscapular brown adipose tissue (IBAT), 2-deoxy-D-glucose (2-DG) was injected into the third cerebral ventricle (icv), lateral hypothalamic area (LHA), and ventromedial hypothalamic nucleus (VMN) of rats. The multiunit discharges of sympathetic nerves to IBAT were recorded electrophysiologically. The icv injection of high and low doses of 2-DG (5.0 and 2.5 mg/rat) suppressed sympathetic nerve activity by 76.9 and 49.8% respectively, 30 min after injection compared with preinjected base line. After the low dose of 2-DG, there was a gradual recovery, but after the high dose recovery did not occur. The unilateral microinjection of 2-DG (0.25 mg/rat) into the LHA induced a similar suppression of sympathetic nerve activity to that observed after icv injection of 10 times as much 2-DG (-25.3%). The injection of vehicle or sucrose into the LHA did not suppress sympathetic nerve activity. The microinjection into the VMN either unilaterally or bilaterally did not suppress sympathetic nerve activity to IBAT. We conclude that the LHA but not the VMH is one site of action of 2-DG. The data are consistent with the hypothesis that the brain senses glucoprivation in the LHA and reduces sympathetic drive to thermogenic tissues such as IBAT. PMID- 2604000 TI - Contribution of hepatic fibronectin synthesis to regulation of plasma fibronectin. AB - Intravenous injection of gelatinized particles, which are phagocytized by the reticuloendothelial system, elicits an acute depletion of plasma fibronectin followed by restoration to normal concentrations in 6-8 h and a rebound elevation at 24 h. We determined the contribution of hepatic fibronectin synthesis to the restoration of plasma fibronectin in rats after particle infusion by measuring the net incorporation of 75selenomethionine into plasma fibronectin during the recovery period. Rats injected intravenously with gelatinized particles had a greater (P less than 0.01) incorporation of labeled 75selenomethionine into fibronectin but less (P less than 0.05) incorporation of 75selenomethionine into total plasma protein than control rats. Inhibition (86%) of hepatic fibronectin synthesis by pretreatment with cycloheximide limited the recovery of fibronectin levels by only 60%, suggesting a source(s) other than hepatic synthesis may contribute to the restoration of plasma fibronectin. Using purified human plasma fibronectin as a tracer in the plasma pool, we found that 26% of the soluble fibronectin consumed from the plasma during particle clearance was subsequently released back into the plasma over a 4-h interval. Tissue analysis indicated that 125I-labeled fibronectin, which was previously incorporated into the tissues, was not released from the tissue pool after the injection of gelatinized particles. Thus the normalization and regulation of plasma fibronectin levels after its acute depletion due to blood-borne particles is a result of 1) an increase in hepatic synthesis of fibronectin, 2) the release of fibronectin previously consumed as an opsonin during particle clearance, and 3) the release of soluble intact fibronectin from a preformed storage pool. PMID- 2604001 TI - Effects of corticotropin-releasing factor on energy balance in rats are sex dependent. AB - The purpose of this study was to investigate the effects of a chronic intracerebroventricular administration of corticotropin-releasing factor (CRF) on energy balance of male and female rats. One week after their delivery to the laboratory, both male and female rats were divided into two groups. One group in each sex was treated with human/rat CRF, while another group was infused with the vehicle. Chronic administration of CRF was accomplished by means of miniosmotic pumps connected to a cannula that was stereotaxically directed into the third ventricle. Food intake and body weight were measured each day during the study. After 14 days of treatment, the rats were killed by decapitation. Energy, fat, and protein contents of the carcasses were quantified. Serum testosterone and estradiol were assayed in males and females, respectively. Administration of CRF significantly reduced body weight gain and food intake in male rats. No significant difference in those variables was observed between female rats treated with CRF and their controls infused with saline. Similarly, metabolizable energy intake and body energy gain were reduced in male rats infused with CRF, whereas no difference was observed between female animals treated with CRF and those infused with saline. In male rats, body fat and body protein contents were lower in CRF-treated than in saline-infused rats. In female rats, CRF did not affect body composition. Serum testosterone in male rats and serum estradiol in female animals were reduced after chronic infusion of CRF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2604002 TI - Axons of passage may be responsible for fastigial nucleus pressor response. AB - Bilateral destruction of perikarya in the fastigial nucleus (FN) of the rat with the cytotoxic agent kainic acid (0.5 mg) did not alter the blood pressure (BP) increases observed during monopolar electrical stimulation (100 microA, 50 Hz, 0.5-ms pulse width) of this region. BP increases in control animals were 30 +/- 8 mm Hg, whereas BP increased 30 +/- 7 mmHg in kainic acid-lesioned rats. Furthermore, picrotoxin (100 ng) and muscimol (25 ng) microinjected unilaterally into the FN of conscious, unrestrained rats produced postural asymmetry but no change in BP or heart rate. These data suggest that the FN pressor response may be due, at least in part, to stimulation of axons of passage. PMID- 2604003 TI - Effects of m-chlorophenylpiperazine on penile and bladder function in rats. AB - The effects of m-chlorophenylpiperazine (MCPP), a serotonin agonist, on spontaneous and evoked neural firing in nerves supplying the penis and bladder were examined in the urethan-anesthetized rat. MCPP (0.1-10 mg/kg iv) elicited, after a 2- to 4-min delay, an increase in spontaneous firing in cavernous nerves but no detectable firing in bladder nerves. The cavernous nerve firing was accompanied by an increase in intracavernous pressure and a depression of rhythmic bladder activity. Administration of ganglionic-blocking agents or transection of peripheral nerves revealed that the cavernous nerve discharge was mediated by activation of pre-ganglionic cholinergic pathways in the pelvic nerve. The effects of MCPP were noted in intact as well as in acute and chronic spinal rats and were prevented by the administration of the serotonin (5-HT) antagonist, metergoline (3 mg/kg im). These data indicate that pharmacological activation of 5-HT receptors, possibly of the 5-HT1B subtype, can facilitate the sacral preganglionic outflow to the penis and inhibit bladder activity. PMID- 2604004 TI - Role for central angiotensin II in control of blood pressure during pregnancy. AB - It is known that the pressor response to intravenous angiotensin II (ANG II) is blunted in pregnancy. In the present study we examined the pressor response to intracerebroventricular ANG II to determine whether central ANG II effects are also attenuated in conscious pregnant rats. Two to three days before experimentation, animals were instrumented with arterial and venous catheters and a ventricular guide cannula. Pressor responses to 10, 50, and 100 ng iv of ANG II, and 30, 100, and 300 ng iv of norepinephrine were significantly reduced in pregnant animals. The pressor response to 5, 20, and 50 ng iv of vasopressin was not attenuated in pregnant rats. The pressor response to intracerebroventricular 100 ng ANG II was significantly increased in pregnancy. Blockade of the vasopressin V1 receptor and the sympathetic ganglia indicated that the greater pressor response to intracerebroventricular ANG II in pregnancy may be the result of a larger contribution by the sympathetic nervous system. We conclude that the central effects of ANG II are augmented in pregnancy, suggesting a significant role for central ANG II in blood pressure regulation. PMID- 2604005 TI - Endogenous cholecystokinin does not decrease food intake or gastric emptying in fasted rats. AB - To investigate the hypothesized inhibitory effect of cholecystokinin (CCK) released from the small intestine on food intake and gastric emptying, we infused soybean trypsin inhibitor (STI) into the stomach or duodenum of male rats deprived of food for 17 h. Intraduodenal infusions of STI (100-200 mg) before real or sham feeding, or during sham feeding, had no effect on food intake. Intragastric infusions of STI (100-200 mg) also had no effect on gastric emptying. Identical infusions of STI, however, increased bioassayable plasma CCK six to ninefold. The failure of endogenous, small intestinal CCK released by STI to decrease food intake or to decrease gastric emptying is evidence against the hypothesis that the inhibitions of food intake and of gastric emptying are physiological functions of small intestinal CCK in food-deprived rats. In contrast to the negative results with STI, administration of exogenous CCK-8 (2-4 micrograms/kg ip) significantly inhibited food intake and gastric emptying despite producing smaller increases of plasma CCK than STI produced. The reason for the differential effects of exogenous and endogenous CCK is not clear and requires further investigation. PMID- 2604006 TI - Effects of spinal cord transection on sympathetic discharge in decerebrate unanesthetized cats. AB - Previous experiments in our laboratory have shown that discharge of splenic, mesenteric, and splanchnic nerves is well maintained after spinal cord transection in chloralose-anesthetized cats (8, 9, 11). The primary purpose of this investigation was to determine if maintained sympathetic discharge could be observed after spinal transection in the absence of chloralose anesthesia. In cats anesthetized with alphaxalone-alphadolone, changes in splanchnic discharge, blood pressure, and heart rate caused by decerebration and removal of the forebrain were observed. This procedure decreased blood pressure, increased heart rate, and had no immediate effect on sympathetic discharge or its rhythm (assessed by power density spectral analysis). One hour after decerebration and termination of anesthesia, splanchnic discharge had increased by approximately 36%. Next, effects of spinal cord transection on discharge of splanchnic, mesenteric, and renal nerves were observed in the decerebrate-unanesthetized cats. Splanchnic discharge decreased by 50%, mesenteric nerve discharge was unchanged, and renal nerve discharge decreased by 97%. Therefore, splanchnic nerve discharge was not as well maintained in decerebrate-unanesthetized cats as it had been in chloralose-anesthetized animals, and the remaining splanchnic discharge appeared to affect mesenteric nerves preferentially. Finally, spectral analysis of the splanchnic discharge demonstrated that before cord transection, most of the signal was in the 0- to 6-Hz frequency range, whereas after transection the proportion of signal in this frequency range was significantly reduced and the proportion in higher frequencies (7-25 Hz) was significantly increased. This loss of low-frequency rhythmicity is consistent with findings in our previous studies in chloralose-anesthetized cats. PMID- 2604007 TI - Bladder contractions and micturition in fetal sheep: their relation to behavioral states. AB - Fetal bladder contractions, indicative of micturition (voiding), and behavioral states were monitored in unanesthetized fetal sheep in utero during the last third of gestation. Fetal voids began during low-voltage electrocortical activity (LV ECoG) at a greater frequency (91.4 +/- 1.0%) than expected (57.2%) and began during high-voltage electrocortical activity (HV ECoG) with a lower frequency (8.7 +/- 1.0%) than expected (42.8%). Fetal voids began significantly sooner after the onset of LV ECoG (5.84 +/- 0.13 min) than after the onset of HV ECoG (10.88 +/- 0.04 min). Electroocular and nuchal muscle activities were associated with 96.2 and 66.0% of the voids, respectively, but there was no significant association between fetal voiding and swallowing episodes. Abolition of spontaneous voiding, by urine drainage (24 h), caused no significant differences, relative to a 24-h control period, in the duration or number of episodes of LV or HV ECoG or percentage of time spent in these states. Also, induction of voiding by infusing saline into the bladder did not significantly alter the time to the next change of ECoG state. However, the mean time to the next void and the mean volume of saline infused into the bladder to induce voiding tended to be less during LV ECoG than HV ECoG, although not significantly less. Our data show that most spontaneous voids in the fetus begin during LV ECoG, suggesting that voiding is regulated by descending information from the brain. Furthermore, these experiments demonstrate that fetal bladder contractions and voiding, either spontaneous or induced, do not influence the normal cycling of fetal ECoG states. PMID- 2604008 TI - Regional differences in fat pad responses to short days in Siberian hamsters. AB - Siberian hamsters exhibit decreased body weight and fat after initial exposure to short photoperiods and increased body weight and fat after extended short photoperiod exposure. The purpose of the present experiments was to determine if uniform changes in white adipose tissue (WAT) pad weights and lipid metabolism correspond to these short photoperiod-induced changes in body fat. Carcass lipid content and testes and fat pad weights [retroperitoneal WAT (RWAT), epididymal WAT (EWAT), and inguinal and dorsal subcutaneous WAT, respectively] were decreased in male hamsters relative to their long day counterparts after 6 and 12 wk of short-day exposure. Moreover, EWAT and RWAT weight, EWAT specific lipoprotein lipase activity, and specific and total lipogenesis were disproportionately decreased relative to the subcutaneous fat pads. The changes in fat pad weight and metabolism were generally reversed coincident with the return to a long-day-like reproductive status after prolonged short-day exposure (24 and 30 wk). In a less detailed experiment, female Siberian hamsters had decreased body, fat pad, and uterine weights after 6 wk of short-day exposure; however, no fat pad-specific changes in weight were observed. The results of these experiments demonstrate that short-day-exposed male Siberian hamsters may be a useful model for examining mechanisms underlying fat pad-specific responses. In addition, gender appears to influence the pattern of short-day-induced lipid depletion in this species. PMID- 2604009 TI - Mobilization of calcium, phosphorus, and magnesium by embryonic alligators (Alligator mississippiensis). AB - The yolk of an alligator (Alligator mississippiensis) egg contains approximately 115 mg of Ca, 180 mg of P, and 17 mg of Mg at oviposition. This compartment is the primary (or sole) source of P and Mg for the forming embryo. Both of these elements are depleted rapidly from the yolk once the embryo enters the growth phase of development. The yolk also is an important source of Ca for the embryo, particularly during the first two-thirds of incubation. During the last trimester of development, however, the embryo supplements Ca from the yolk with Ca mobilized from the eggshell. Indeed, more Ca is withdrawn from the eggshell during the last 2 wk of incubation than can be used by the embryo in skeletogenesis. The excess Ca is stored in the yolk, thereby causing net transfer of Ca to shift from withdrawal from the yolk to deposition in the yolk. Consequently, the residual yolk in the hatchling alligator contains a substantial reserve of Ca to support skeletal growth during the neonatal period. The pattern of mobilization and deposition of Ca during embryogenesis in alligators is similar to that characterizing avian embryos, but is distinct from that characterizing embryos of all other oviparous reptiles. PMID- 2604010 TI - Effect of fall mating on ovarian development in the red-sided garter snake. AB - Although spring mating is an important factor in initiating vitellogenesis in female red-sided garter snakes (Thamnophis sirtalis parietalis), some females can become vitellogenic without having mated in the spring. Two hypotheses have been proposed to explain this phenomenon: 1) long-term storage of copulatory stimuli from mating the previous fall, or 2) additional cue(s) overcoming the lack of mating to stimulate vitellogenesis. Through oviductal biopsy, the presence of sperm in females returning to the hibernaculum in the fall was assessed. Laparotomies performed just before and 6 wk after hibernation indicated that although fall mating may stimulate slight ovarian development in the fall, there appears to be no effect of fall mating on spring ovarian recrudescence. Spring mating seems to be the most important factor in determining ovarian maturation. Therefore, it appears that there is no long-term storage of copulatory cues and that other as yet unknown cues are responsible for initiating vitellogenesis in spring unmated females. PMID- 2604011 TI - Structure-function analyses of brain angiotensin control of pressor action in rats. AB - The present investigation examined the relative pressor potencies of intracerebroventricularly infused angiotensin (ANG) II, successively shortened COOH-terminal fragments through ANG II(5-8), and the analogues [Sar1]ANG II through [Sar1]ANG II(5-8). The results indicate that ANG II, ANG III, [Sar1]ANG II, and [Sar1]ANG III were identical with respect to pressor responses in the alert free-moving rat. In addition, ANG II(3-8) and [Sar1]ANG II(3-8) exhibited 68-70% of the activity of the above compounds, whereas the activity of the shorter COOH-terminal fragments dropped to approximately 13-35%. Pressor responses caused by each of the active forms of angiotensin could be substantially reduced by pretreatment with the specific angiotensin receptor antagonist [Sar1,Thr8]ANG II (Sarthran), suggesting either that these ligands are acting at multiple receptors for ANG II and its fragments, which are all blocked by Sarthran, or that the ligands are acting at a common receptor site. These results, coupled with other recent findings, suggest that the brain angiotensin receptor may be designed to preferentially interact with ANG II and/or ANG III or other angiotensin analogues that structurally resemble ANG III such as [Sar1]ANG II. It is concluded that ANG III's importance as a centrally active ligand has been underestimated and that ANG III may be an active form of angiotensin in the brain. PMID- 2604012 TI - Importance of prostaglandins in hypertension during reduced uteroplacental perfusion pressure. AB - Uteroplacental ischemia causes hypertension in various species but the mechanisms involved are not known. These studies were designed to test the hypothesis that the systemic hypertension that occurs during reduced uteroplacental perfusion pressure is mediated by the prostaglandin system. Trained chronically instrumented pregnant dogs in the last third of gestation were studied. When uterine perfusion pressure was reduced to 60 mmHg for 60 min using an inflatable aortic occluder placed distal to the renal but proximal to the uterine and ovarian arteries, systemic arterial pressure increased from 95 +/- 5 to 110 +/- 7 mmHg. On another day in the same animals, the prostaglandin system was blocked with meclofenamate. Subsequent reduction of uterine arterial pressure caused no significant change in systemic pressure, from 96 +/- 4 to 99 +/- 6 mmHg, suggesting an important role for the prostaglandin system in mediating the normal response. In additional experiments, the thromboxane receptor antagonist SQ 29,548 was given. Arterial pressure averaged 94 +/- 5 mmHg after administration of SQ 29,548 and did not change significantly when uterine perfusion pressure was reduced during SQ 29,548. These data suggest that at least one component of the prostaglandin system, thromboxane, contributes to the rise in systemic arterial pressure during reduced uteroplacental perfusion pressure. PMID- 2604013 TI - Ion leakage is reduced during anoxia in turtle brain: a potential survival strategy. AB - The turtle brain maintains ATP levels, ion homeostasis, and some neural function during prolonged anoxia despite significant decreases in the rate of ATP production. To test the hypothesis that reduced ATP production during anoxia was compensated partly by conserving energy through reduced ion leakage, the rate of K+ leakage was measured in normoxic and anoxic turtle brains in which Na(+)-K(+) adenosinetriphosphatase was inhibited with ouabain. Rates of K+ leakage were significantly lower in brains subjected to 2 h of anoxia than in normoxic brains. These data support the suggestion that reduced ion leakage is an important mechanism for energy conservation during anoxia. PMID- 2604014 TI - If we are going to teach graduate students how to teach ... PMID- 2604015 TI - An initiation into teaching for graduate students. AB - The Physiology Department at State University of New York at Buffalo offers a one credit course that is intended to improve communication skills and to foster a problem-solving approach to the teaching/learning process. In the course, students practice lecturing, prepare examination questions, and participate in discussions of various teaching problems. PMID- 2604016 TI - Electricity and the body: a precollege demonstration laboratory. AB - The active recruitment of students to scientific careers is essential to the continued health of the basic medical sciences. One step in this process involves an early exposure to the practice and possibilities of scientific investigation. Physiology faculty of colleges and professional schools are uniquely poised to demonstrate the importance of science to younger students. This report describes a laboratory demonstration that is designed for groups of middle-school and high school students as a part of a medical school tour. With appropriate modifications, a similar approach can be used to demonstrate the principles of scientific investigation to students at any level. Subsequent discussions can be used to illustrate the potential benefits of medical research. Presentations such as the one contained in this paper may aid in the recruitment of future physiologists and physicians.